预约演示
更新于：2026-07-02
Lenvatinib mesylate
甲磺酸仑伐替尼
更新于：2026-07-02
概要
基本信息
药物类型 小分子化药 |
别名 lenvatinib、lenvatinib mesilate、Lenvatinib mesilate (JAN) + [19] |
作用方式 拮抗剂、抑制剂 |
作用机制 FGFR1拮抗剂(成纤维细胞生长因子受体-1拮抗剂)、FGFR2拮抗剂(成纤维细胞生长因子受体-2拮抗剂)、FGFR3拮抗剂(成纤维细胞生长因子受体-3拮抗剂) |
原研机构 |
最高研发阶段批准上市 |
首次获批日期 美国 (2015-02-13), |
最高研发阶段(中国)批准上市 |
特殊审评突破性疗法 (美国)、加速批准 (美国)、孤儿药 (美国)、附条件批准 (中国)、特殊审批 (中国)、孤儿药 (日本)、孤儿药 (澳大利亚)、优先审评 (澳大利亚)、优先审评 (中国) |
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结构/序列
分子式C22H23ClN4O7S |
InChIKeyHWLFIUUAYLEFCT-UHFFFAOYSA-N |
CAS号857890-39-2 |
关联
771
项与 甲磺酸仑伐替尼 相关的临床试验NCT05077215
A Phase 3, Randomized, Open-Label, Active-Controlled, Superiority Trial of EG007, Added to the Combination of Lenvatinib Plus Pembrolizumab vs. Lenvatinib Plus Pembrolizumab in Patients With Advanced Endometrial Cancer
This is a Phase 3, multicenter, randomized, open-label trial to evaluate whether EG-007 plus Len+Pem is superior to Len+Pem alone in patients with advanced endometrial cancer (Stage III or IV). This trial will be preceded by a safety lead-in study with up to 28 patients (the safety lead-in is a separate, free-standing protocol).
Approximately 450 patients will be randomized equally (1:1) to receive EG-007 plus Len+Pem or Len+Pem alone. The randomization will be stratified by the following stratification factors:
* Diagnosis Classification (advanced Stage III/IV vs. recurrent endometrial cancer)
* ECOG score at baseline (0 vs 1)
* Geographic region (Asia vs ROW)
Approximately 450 patients will be randomized equally (1:1) to receive EG-007 plus Len+Pem or Len+Pem alone. The randomization will be stratified by the following stratification factors:
* Diagnosis Classification (advanced Stage III/IV vs. recurrent endometrial cancer)
* ECOG score at baseline (0 vs 1)
* Geographic region (Asia vs ROW)
开始日期2026-12-01 |
申办/合作机构 |
NCT07680088
A Multicenter Single-arm Phase 2 Study of Pembrolizumab and Lenvatinib in Previously Treated Inoperable or Advanced Anal Squamous Cell Cancer
The goal of this clinical trial is to see the safety and efficacy of pembrolizumab and lenvatinib in patients with anal squamous cell cancer that cannot be removed through surgery or is spread to other organs. Eligible participants should have also received some form of standard therapy previously for their advanced cancer.
Participants will be required to come for a clinic visit and infusion of pembrolizumab. Lenvatinib will be taken by mouth at home based on direction provided by physicians and research team.
Participants will be required to come for a clinic visit and infusion of pembrolizumab. Lenvatinib will be taken by mouth at home based on direction provided by physicians and research team.
开始日期2026-09-30 |
NCT07540832
An Open-Label Phase 2 Study of WGI-0301 Plus Lenvatinib in Patients With Advanced Hepatocellular Carcinoma as Second Line Therapy
This is a Phase II study being done at several hospitals without using a placebo. It will look at how safe and tolerable the drug WGI-0301 is when given together with Lenvatinib, how the body processes and responds to WGI-0301, and whether this combination shows early signs of working in people with advanced liver cancer.
开始日期2026-09-01 |
申办/合作机构 |
100 项与 甲磺酸仑伐替尼 相关的临床结果
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100 项与 甲磺酸仑伐替尼 相关的转化医学
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100 项与 甲磺酸仑伐替尼 相关的专利（医药）
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3,803
项与 甲磺酸仑伐替尼 相关的文献（医药）2026-12-31·ANNALS OF MEDICINE
Systematic meta-analysis of the toxicities and side effects of the targeted drug lenvatinib
Review
作者: Liu, Huihui ; Cui, Chao ; Wang, Kai ; Li, Qingwei ; Sun, Yu ; Gao, Shuai ; Shi, Jingfei
BACKGROUND:
Lenvatinib, an effective targeted drug for various cancers, has clinical medication safety concerns due to its toxicities and side effects.
OBJECTIVE:
This study evaluated lenvatinib-induced any adverse events (any AEs) and nine aspects: vascular toxicities related to the circulatory system (vascular toxicities, blood system, and heart), toxicities of the skin and its appendages (skin/subcutaneous tissue and taste system), toxicities of the respiratory system (respiratory, thoracic, and mediastinal and respiratory tract), toxicities of the nervous system (nervous system and general), toxicities of the digestive system (gastrointestinal and liver), toxicities of the urinary system, toxicities of the endocrine and metabolic system (endocrine and metabolism/nutrition), toxicities of the musculoskeletal system, and other severe toxicities. Toxicities and side effects were stratified by severity into any and ≥3 grades for analysis.
PATIENTS/MATERIALS AND METHODS:
Multiple databases were searched for lenvatinib cancer clinical studies (cohort studies and randomized controlled trials) from inception to December 31, 2024; toxicity and side effect data were extracted and analyzed.
RESULTS:
Nine high-quality studies were included, showing that lenvatinib is effective in cancers but has notable toxicities. Taking hypertension as an example, for any grade, the risk ratio (RR) was 2.34 with a 95% confidence interval (CI) of [2.09, 2.62], a Z-value of 14.74, and a P-value <0.00001; for grade ≥3, the RR was 2.60 with a 95% CI of [2.21, 3.06], a Z-value of 11.44, and a P-value <0.00001.
CONCLUSION:
Lenvatinib is effective for cancer but toxic, and this study supports its rational clinical use.
2026-12-31·JOURNAL OF MEDICAL ECONOMICS
Cost-effectiveness analysis of atezolizumab and bevacizumab as first-line systemic therapy in unresectable hepatocellular carcinoma in Malaysia
Article
作者: Chaiyakunapruk, Nathorn ; Patikorn, Chanthawat ; Sulaiman Shah, Audi Adawiah ; Wong, Yoke Fui ; Mohamed, Rosmawati
AIM:
This study aims to evaluate the cost-effectiveness of atezolizumab plus bevacizumab as first-line systemic therapy for unresectable hepatocellular carcinoma (uHCC) in Malaysia, compared with the current standard treatments in the Malaysian Ministry of Health (MOH) to inform public healthcare decision‑making.
MATERIALS AND METHODS:
A cost-effectiveness analysis was conducted from the MOH perspective, following the national pharmacoeconomic guidelines (2019). The study compared atezolizumab plus bevacizumab with sorafenib and lenvatinib, respectively, using a partitioned survival model to project health outcomes and costs over a lifetime horizon. Clinical efficacy data were sourced from published trials and network meta-analyses. Cost inputs reflected local healthcare resource use and prices, using 2024 Malaysian Ringgit values inflated via the Consumer Price Index for Health. Costs and outcomes were discounted at 3% annually. Deterministic and probabilistic sensitivity analyses were performed to assess the impact of key parameter uncertainties on the results.
RESULTS:
Atezolizumab plus bevacizumab provided the highest quality-adjusted life years (QALYs) and life years compared to sorafenib and lenvatinib. Sorafenib was dominated by lenvatinib due to lower QALYs and higher costs and excluded from further analysis. Compared to lenvatinib, atezolizumab plus bevacizumab yielded 0.873 additional QALYs and RM 44,863 additional cost, resulting in an incremental cost-effectiveness ratio (ICER) of RM 51,399 per QALY gained (∼0.906 GDP/capita at Malaysia's 2024 GDP/capita RM 56,734).
CONCLUSIONS:
Atezolizumab plus bevacizumab is cost-effective compared to lenvatinib and sorafenib across willingness-to-pay (WTP) values of one to three times Malaysia's GDP per capita. These findings provide evidence to inform public health policy that expanding funding and adoption of atezolizumab plus bevacizumab is likely to improve health outcomes cost-effectively.
2026-12-31·CANCER BIOLOGY & THERAPY
Lenvatinib potentiates the antitumor efficacy of combined radiotherapy and PD-L1 blockade in lung adenocarcinoma
Article
作者: Li, Tao ; Zhang, Shichuan ; Zhang, Xue ; Li, Linjie ; Xiao, Ling ; Tang, Chengxi ; Liu, Yudi ; Lyu, Jiahua ; Nie, Xinyu ; Huang, Jianming
BACKGROUND:
The potential of Lenvatinib to synergize with combined radiotherapy and immunotherapy in LUAD remains incompletely characterized.
METHODS:
We investigated Lenvatinib's effects on radiation-induced PD-L1 in LUAD cells and VEGFR2 in HUVECs via Western blot, VEGFA expression via RT-qPCR/ELISA, and angiogenesis via immunofluorescence. LUAD-HUVEC crosstalk was modeled in vitro. In C57BL/6 mice bearing LUAD tumors, we evaluated the efficacy of RT and anti-PD-L1 with or without Lenvatinib, monitoring tumor growth, survival, and profiling the tumor microenvironment by mIHC and flow cytometry.
RESULTS:
Lenvatinib suppressed radiation-induced PD-L1 and VEGFR2 expression, inhibited angiogenesis, and disrupted HUVEC-facilitated LUAD proliferation. The triple-combination (RT + anti-PD-L1 + Lenvatinib) significantly suppressed tumor progression (P < 0.05) and extended median survival (34 vs. 29.5 days, P < 0.05) versus dual therapy. It also enhanced intratumoral CD8+ T-cell infiltration and cytotoxicity, promoted M1-like macrophage polarization, and reduced regulatory T cell frequency and microvessel density.
CONCLUSIONS:
Lenvatinib potentiates RT and anti-PD-L1 therapy in LUAD through dual immune-vascular modulation, supporting the clinical translation of this triple-combination strategy.
2,434
项与 甲磺酸仑伐替尼 相关的新闻（医药）2026-07-01
·今日头条
ESMO 2026妇科肿瘤大会已于6月17-19日在丹麦哥本哈根召开完毕，本届大会共有近百项卵巢癌相关研究报告呈现，来看看有没有你感兴趣的内容。
有能力的读者可以直接访问官网链接获取完整报告： https://ow.ly/116M50ZfwEM，或者也可以评论区留言报告编号，后续我们挑大家比较关心的研究作分享。
一 一线治疗：我们能否改进当前的治疗算法？
01 卵巢癌是否存在一些生物标志物可用于选择最佳治疗方案？
02 一线卵巢癌的当前维持治疗策略：多少才算过度？
03 靶向有效载荷：抗体偶联药物（ ADC ）在卵巢癌一线治疗中的应用
二 铂耐药卵巢癌：治疗策略与未满足的需求
04 铂耐药卵巢癌的生物学特征
05 铂耐药卵巢癌患者的治疗选择
06 正在进行的关于铂耐药卵巢癌中基于生物学的精准治疗策略的研究
07 铂耐药复发患者的临床病例：化疗药物和靶向药物毒性管理的实用技巧
三 快速口头报告专场
08 KELIM 化疗敏感性与化疗强化（标准或剂量密集型；有 / 无贝伐珠单抗）生存获益的连续关系： ICON8 & 8B 研究
09 来自复发卵巢癌（ OC ） III 期 ANITA （ ENGOT-Ov41/GEICO 69-O ）试验的预后循环免疫蛋白特征验证及探索性动态生物标志物分析
10 B7-H4 靶向抗体偶联药物（ ADC ） Mocertatug rezetecan （ Mo-Rez ）在铂耐药卵巢癌（ PROC ）和子宫内膜癌（ EC ）中的应用： BEHOLD-1 研究的额外数据
11 叶酸受体 α （ FRα ）表达的铂敏感卵巢癌（ PSOC ）患者接受索米妥昔单抗（ MIRV ）联合卡铂（ Carbo ）治疗中肺炎的概述
12 ATHENA-MONO/GOG-3020/ENGOT-ov45 研究中新诊断晚期卵巢癌（ AOC ）患者后续抗癌治疗（ SACT ）情况
四
液体活检和
ctDNA
在妇科肿瘤监测与指导治疗选择中的临床应用
13 卵巢癌 ctDNA 的全基因组测序
五
HER2
：妇科恶性肿瘤中新兴的可靶向驱动因素
14 HER2 阳性妇科恶性肿瘤患者的生物学背景和临床病例
15 HER2 过表达的妇科癌症：靶向治疗的临床适应症
16 展望未来：利用生物标志物以及多种方法来优化患者选择，从而改善治疗效果
六 疑难组织学类型
17 卵巢透明细胞癌治疗进展
18 卵巢癌肉瘤的治疗策略
19 低级别卵巢癌的治疗
七 新药研发：深入探究肿瘤生物学机制
20 细胞周期中 CDK2/Cyclin E 复合物的重要作用，使其成为新的治疗靶点
21 超越检查点抑制剂的免疫治疗方法： T 细胞衔接器和双特异性抗体的作用
22 即将崛起的抗体偶联药物（ ADC ）：我们能否靶向肿瘤微环境？
八 ePoster
专场
23 卵巢生殖细胞肿瘤：在资源有限的情况下也能取得良好的治疗效果
24 低级别浆液性卵巢癌中孕激素受体表达与内分泌治疗结局
25 BRCA 突变类型及功能域与卵巢癌无进展生存期的关联：一项真实世界观察性研究
26 奥拉帕利维持治疗：超越预期的维持效果
27 卵巢癌中 PARP 抑制剂治疗相关的髓系肿瘤：来自印度东部的多中心病例研究
28 PARP 抑制剂治疗期间 TP53 克隆性造血与治疗相关髓系肿瘤的关联
29 按组织学类型和 BRCA 状态划分的 I–II 期上皮性卵巢癌的病程模式与晚期复发风险
30 卵巢癌的双重靶向：一种联合前动力蛋白 2 和 RAGE-ADC 的方法
31 晚期上皮性卵巢 / 输卵管癌腹膜癌患者接受细胞减灭术（ CRS ）时使用封闭式 CO₂ 再循环装置的腹腔热灌注化疗（ HIPEC ）：单中心可行性经验
32 老年晚期卵巢癌患者间歇性肿瘤细胞减灭术无生存获益：来自真实世界实践的证据
33 索米妥昔单抗（ MIRV ）在铂耐药高级别浆液性卵巢癌（ HGSOC ）中的眼部毒性：单中心真实世界管理经验
34 妊娠期卵巢癌：来自系统评价和荟萃分析的母体与胎儿结局
35 推进遗传性卵巢癌的多因素风险评估：癌症使命项目 DISARM 的临床研究
九 海报展示专场
36 高级别浆液性卵巢癌中叶酸受体 α 表达与取样变量、同源重组缺陷及无铂间期的关联
37 患者与医生对原发晚期卵巢癌治疗的期望
38 复发性子宫内膜样卵巢癌：长期生存者
39 通过抑制 WEE1蛋白，针对 透明细胞癌中的细胞周期脆弱性进行靶向治疗
40 NKT 细胞在塑造高级别浆液性卵巢癌免疫抑制微环境中的作用
41 德国复发卵巢癌（ OC ）患者的治疗与结局： AGO 研究组 QS Ovar 项目
42 晚期卵巢癌中 HRD 状态与临床结局的不一致： 80 例患者的真实世界回顾性队列研究
43 晚期上皮性卵巢癌（ EOC ）中 PARP 抑制剂（ PARPi ）后的治疗相关髓系肿瘤（ t-MN ）
44 晚期卵巢癌一线维持治疗的比较疗效与安全性： 16 项 III 期试验的生物标志物分层贝叶斯网络荟萃分析
45 新辅助化疗期间动态 ctDNA 和 CA-125 动力学变化作为高级别浆液性卵巢癌间歇性肿瘤细胞减灭和无进展生存预测因子的系统评价与荟萃分析
46 平均红细胞体积早期升高作为尼拉帕利临床获益的生物标志物： EVINO 项目初步结果
47 整合 CA-125 反应和残留病灶预测卵巢癌生存：真实世界风险模型
48 用于识别卵巢癌 PI3K 通路生物标志物和治疗候选药物的精准医学与系统生物学分析
49 阐明卵巢癌免疫和肿瘤微环境的动态变化
50 靶向 SIK2 促进 CD8+ T 细胞浸润并增强卵巢癌免疫治疗敏感性的机制研究
51 NOGGO PERCEPTION 研究结果：帕博利珠单抗联合化疗治疗铂敏感复发低级别浆液性卵巢癌的 II 期研究
52 ixotatug vedotin（ TORL-1-23 ），一种 Claudin 6 靶向 ADC ，联合贝伐珠单抗治疗复发卵巢癌的初步安全性和疗效
53 Sofe-M ，一种靶向叶酸受体 α （ FRα ）的抗体偶联药物（ ADC ）在晚期卵巢癌（ OC ）中的 I 期研究更新
54 妇科恶性肿瘤早期临床试验： 13 年单中心经验
55 ZW191 在 I 期研究中按叶酸受体 α （ FRα ）表达水平的分层疗效分析
56 NeoPembrOV/GINECO 试验中不可手术高级别浆液性卵巢癌原发灶在 NACT 前后临床相关抗体偶联药物靶点的 RNA 测序图谱
57 接受二次肿瘤细胞减灭术的复发卵巢癌患者中叶酸受体 α （ FRα ）表达的变化 ：真实世界分析
58 爱丁堡癌症中心早期（ 1c-2 期）透明细胞卵巢癌的辅助放疗结局
59 成人卵巢颗粒细胞瘤中辅助 BEP/EP 与卡铂 - 紫杉醇的多中心生存与毒性分析
60 瑞拉可利兰（ relacorilant ） + 白蛋白紫杉醇在 ≥65 岁铂耐药卵巢癌（ PROC ）患者中的疗效与安全性： III 期 ROSELLA 研究（ GOG-3073, ENGOT-ov72, APGOT-Ov10 ）
61 年龄对晚期卵巢癌患者治疗模式、毒性和结局的影响：多中心真实世界研究亚组分析
62 索米妥昔单抗在卵巢癌中的眼部毒性：真实世界分析
63 尼拉帕利在日本复发卵巢癌患者中的安全性和疗效：铂敏感复发的维持治疗及后线单药治疗
64 交界性和 I 期浸润性卵巢肿瘤的临床与超声特征：多中心回顾性研究
65 晚期卵巢癌长期无病生存的决定因素：真实世界分析
66 卵巢癌是否已成为分子层面的慢性病？一项真实世界治疗强度分析
67 超越年龄看晚期卵巢癌：单中心真实世界分析
68 临床淋巴结阴性卵巢癌（ FIGO I-III 期）的淋巴结切除术：来自巴登 - 符腾堡癌症登记的人群分析
69 白蛋白紫杉醇与标准化疗方案在铂耐药卵巢癌患者中的真实世界疗效比较（ COMPASS 2.0 ）
70 接受卢卡帕利的患者真实世界毒性：双中心回顾性研究。是否应在老年患者中考虑提前调整剂量？
71 nesuparib（ JPI-547 ）联合贝伐珠单抗维持治疗既往接受过 PARP 抑制剂且对最后一次铂类治疗有反应的复发卵巢癌患者的开放标签、剂量探索、随机 II 期研究
72 NCT03878849 ：stenoparib /2X-121 （一种新型 PARP 和 WNT 通路双重抑制剂）在铂耐药 / 不适合铂类治疗卵巢癌患者中的 II 期试验
73 HWK-016 （一种新一代 MUC16 靶向抗体偶联药物 ADC ）在晚期实体瘤患者中的 I 期研究
74 farletuzemab ecteribulin （ FZEC ），一种叶酸受体 α （ FRα ）靶向抗体偶联药物（ ADC ），单药及联合仑伐替尼（ LEN ）治疗铂耐药卵巢癌（ PROC ）的开放标签、多中心 II 期研究
75 ABBV-901 单药及联合贝伐珠单抗（ Bev ）治疗铂耐药卵巢癌（ PROC ）的 I 期首次人体、开放标签研究
76 MAIA-ovarian （ NCT06888921 ）自适应平台临床试验：评估 COM701 维持治疗在铂敏感复发卵巢癌（ PSOC ）中的安全性和有效性
十
特邀论文报告专场
77 索米妥昔单抗（ MIRV ）联合卡铂（ Carbo ）在叶酸受体 α （ FRα ）阳性铂敏感复发卵巢癌（ PSOC ）中的应用：按既往 PARP 抑制剂（ PARPi ）治疗分层的结局
78 索米妥昔单抗在叶酸受体 α （ FRα ）高表达、适合接受铂类化疗的复发卵巢癌中的随机 II 期试验（ MIROVA/AGO-OVAR 2.34 ）
十一
妇科恶性肿瘤手术领域的进展
79 我们该如何选择适合进行初始肿瘤细胞减灭术或新辅助化疗的患者呢？
80 早期卵巢癌的手术治疗：当需要保护生育能力时该如何处理
十二
晚期
/
复发性子宫内膜癌：如何确定最佳治疗策略
81 我们如何将抗体偶联药物（ ADC ）纳入一线治疗？
十三
复发卵巢癌治疗格局的演进
82 对于铂耐药卵巢癌，是否存在新的的治疗标准？
83 抗体偶联药物（ ADC ）在适合铂类治疗的卵巢癌患者中的作用是什么？
84 抗体偶联药物（ ADC ）在不适合铂类治疗的卵巢癌患者中的作用是什么？
以上为大会卵巢癌相关全部报告，翻译可能有错讹，敬请指正。可以评论区留言你感兴趣的议题，后续我们再作分享解读。感谢大家的关注！
2026-07-01
BMC Medicine [Jour] AND 24[volume] AND 1[issue]（first half of the year）
生物医学中心 - 医学 24卷 1期（上半年）
https://link.springer.com/journal/12916/volumes-and-issues/24-1
369 articles in this issue
Impact of a real-time automatic quality control system for magnetically controlled capsule gastroscopy: a multicenter randomized controlled trial
磁控胶囊胃镜实时自动质量控制系统的效果：一项多中心随机对照试验
Xiaoya WangDawei ShenZhen Li
Research 02 May 2026
Article: 369
Lipid levels and risk-stratified management gaps of dyslipidemia in China
中国血脂水平及血脂异常风险分层管理差距
Long ZhangXu LiuJianping Li
Research 02 May 2026
Article: 368
Medicine price and affordability in China and selected ASEAN countries: a cross-country comparison with forward-looking implications for regional pooled procurement
中国与部分东盟国家的药品价格和可负担性：对区域集中采购前瞻性影响的跨国比较
Zhuangqi LiShuting ZhangBao Liu
Research 02 May 2026
Article: 367
Dementia risk by metabolic health and obesity in two prospective cohorts
两项前瞻性队列研究中代谢健康和肥胖对痴呆风险的影响
Martin NakashElsa Ojalehto LindforsIda K. Karlsson
Research 19 June 2026
Article: 366
Part of 1 collection:Healthy aging and longevity: the role of preventive medicine and risk factors
所属专题合集：健康老龄化与长寿：预防医学和风险因素的作用
Maternal B-vitamin status modifies the risk of congenital heart disease in offspring associated with prenatal persistent organic pollutants exposure
母体B族维生素状况会改变胎儿在宫内持续暴露于有机污染物时先天性心脏病的患病风险
Sainan LiHai LinLinlin Wang
Research 04 May 2026
Article: 365
Obesity-derived metabolites modulate anti-tumor immunity in the tumor microenvironment: from mechanisms to clinical applications
肥胖衍生的代谢产物在肿瘤微环境中调节抗肿瘤免疫：从机制到临床应用
Yihang CaiJunyi JinXiaoying Li
Review 06 May 2026
Article: 364
Part of 1 collection:Tumor microenvironment in cancer therapy
所属专题合集：癌症治疗中的肿瘤微环境
Rational use of expensive medicines in the Netherlands: strategies to improve effectiveness and reduce burden on patients and society – a narrative review
荷兰高价药品的合理使用：提高疗效、减轻患者和社会负担的策略——一项叙述性综述
Bart M.F. PenninxSander W. TasCarla E.M. Hollak
Review 30 April 2026
Article: 363
NMR-based serum metabolite and lipoprotein profiling for endometriosis across clinically relevant and physiological comparator settings: assessment of diagnostic utility and exploratory biological signals
基于核磁共振（NMR）的血清代谢物和脂蛋白谱分析在子宫内膜异位症的临床相关和生理对照情况中的应用：诊断效用的评估和探索性生物信号的发现
Sisi DengAndré KochChristoph Trautwein
Research 17 June 2026
Article: 362
Changes in olfactory function in children and adolescents with obesity following an inpatient weight loss program: a longitudinal study
住院减肥计划后肥胖儿童和青少年嗅觉功能的变化：一项纵向研究
Bea KlosHelene SauerIsabelle Mack
Research 17 June 2026
Article: 361
Part of 1 collection:Weight loss interventions and their health impacts
所属专题合集：减肥干预及其对健康的影响
The neuroimmune axis in breast cancer: from mechanistic insights to clinical applications
乳腺癌中的神经免疫轴：从机制研究到临床应用
Yimao WuKaiyu ZhangMeng-Yao Li
Review 30 April 2026
Article: 360
A biologically informed framework for instrument selection in dietary Mendelian randomization using chemosensory genetics
基于化学感觉遗传学的饮食孟德尔随机化工具选择生物学框架
Liang-Dar HwangCailu LinPaule V. Joseph
Research 01 June 2026
Article: 359
Efficacy and safety of cyclosporine plus luspatercept versus cyclosporine in newly diagnosed non-transfusion-dependent non-severe aplastic anemia: A prospective randomized trial
环孢素联合卢帕塞普特与单用环孢素治疗新发非输血依赖型非重型再生障碍性贫血的疗效和安全性：一项前瞻性随机试验
Zhuxin ZhangQinglin HuBing Han
Research 29 April 2026
Article: 358
Dietary intake and epigenetic aging in an African population: food groups, dietary patterns, and plant-based diets in the RODAM study
非洲人群的膳食摄入与表观遗传衰老：RODAM研究中的食物组、膳食模式与植物性饮食
Naomi C.S. AuwerdaMuhau. M. MungambaFelix P. Chilunga
Research 28 April 2026
Article: 357
Part of 1 collection:Healthy aging and longevity: the role of preventive medicine and risk factors
所属专题合集：健康老龄化与长寿：预防医学与风险因素的作用
Mitoxantrone hydrochloride liposome (Lipo-MIT) combined with capecitabine in HER2-negative advanced breast cancer: a dose-escalation, phase I study
米托蒽醌盐酸盐脂质体（Lipo-MIT）联合卡培他滨治疗HER2阴性晚期乳腺癌：一项剂量递增Ⅰ期研究
Jiaxuan LiuMingxia JiangQiao Li
Research 28 April 2026
Article: 356
Familial healthy aging and longevity: the role of spouses
家族健康衰老与长寿：配偶的作用
Søren NetraAngéline GalvinKaare Christensen
Research 28 April 2026
Article: 355
Part of 1 collection:Healthy aging and longevity: the role of preventive medicine and risk factors
所属专题合集：健康老龄化与长寿：预防医学与风险因素的作用
Peripheral blood biomarkers RCAN1, Clusterin, RAGE, and malondialdehyde for early diagnosis and progression of Alzheimer’s disease
外周血生物标志物RCAN1、Clusterin、RAGE和丙二醛用于阿尔茨海默病的早期诊断与进展监测
Aurora Román-DomínguezCristina Mas-BarguesJosé Viña
Research 27 April 2026
Article: 354
Part of 1 collection:Healthy aging and longevity: the role of preventive medicine and risk factors
所属专题合集：健康老龄化与长寿：预防医学与风险因素的作用
Palliative care for the people without medical insurance in Germany: an empirical ethical approach
德国无医疗保险人群的姑息治疗：一种实证伦理方法
Matthias ZimmerAntonia Sahm
Research 11 June 2026
Article: 353
Part of 1 collection:Palliative care and medicine
所属专题合集：姑息治疗与姑息医学
Maternal factors associate with microbiota-derived extracellular vesicle profiles in pregnancy: a clinical cohort study
妊娠期母体因素与微生物衍生的细胞外囊泡特征的相关性：一项临床队列研究
Jenni TurunenKaisu KyröTerhi Ruuska-Loewald
Research 28 May 2026
Article: 352
Prenatal computed tomography (CT) and risk of congenital heart disease and cerebral palsy: A nationwide mother–child paired cohort study
产前计算机断层扫描（CT）与先天性心脏病及脑瘫风险：一项全国性母子配对队列研究
Tae Wook KangJihye HeoDanbee Kang
Research 27 April 2026
Article: 351
Therapeutic TG2 inhibition reverses systemic multiomic dysregulation in celiac disease
治疗性TG2抑制可逆转乳糜泻的系统性多组学失调
Valeriia DotsenkoHana Hien Leon behalf of the CEC-3 Investigators
Research 24 April 2026
Article: 350
Adulthood stressful life events as predictors of incident cardiovascular disease: insights from two prospective cohorts
成年期应激性生活事件作为心血管疾病新发预测因子：来自两项前瞻性队列的见解
Shuang WuSiqi LyuGregory Y. H. Lip
Research 24 April 2026
Article: 349
Camrelizumab plus apatinib for immune checkpoint inhibitor-naive patients with metastatic clear cell renal cell carcinoma after first-line tyrosine kinase inhibitor treatment failure: a single-arm phase 2 trial
卡瑞利珠单抗联合阿帕替尼用于免疫检查点抑制剂初治转移性透明细胞肾细胞癌一线酪氨酸激酶抑制剂治疗失败后：一项单臂Ⅱ期试验
Xiuyu CaiXia ZhengPei Dong
Research 24 April 2026
Article: 348
Introducing the need for a consensus-based framework for protocol modifications to improve trial trustworthiness
提出建立基于共识的方案修改框架以提升临床试验可信度的必要性
Cora BurgwinkelManon GicquelClara Locher
Debate 24 April 2026
Article: 347
Modelling the epidemic dynamics of HPV among women in China and optimization of ongoing cervical cancer elimination strategies
中国女性人群HPV流行动力学建模及宫颈癌消除策略优化
Yuwei LiYi-Fan LinJianxin Zhen
Research 22 April 2026
Article: 346
Multiparameter concept-based interpretable model for early breast cancer diagnosis and structured reporting: a multi-center, multi-reader, radiologist-in-the-loop study
基于多参数概念的可解释模型用于早期乳腺癌诊断与结构化报告：一项多中心、多读者、放射科医师参与的研究
Jiao QuYang LiuSu Lui
Research 23 April 2026
Article: 345
Blood-based DNA methylation marker model for short-term and long-term lung cancer risk prediction
基于血液DNA甲基化标志物模型的肺癌短期与长期风险预测
Megha BhardwajYi-Qian SunHermann Brenner
Research 06 June 2026
Article: 344
Integrated serum proteomic and liver genomic analyses identify molecular signatures associated with metabolic dysfunction-associated steatotic liver disease: a multi-cohort study
整合血清蛋白质组学与肝脏基因组学分析鉴定与代谢功能障碍相关脂肪性肝病相关的分子特征：一项多队列研究
Jinjian XuWanglong GouYu-ming Chen
Research 17 April 2026
Article: 343
Predicting amyotrophic lateral sclerosis stage based on multi-parameter ultrasound: development and validation of an interpretable machine learning model
基于多参数超声预测肌萎缩侧索硬化症分期：可解释机器学习模型的构建与验证
Tianhua YangYing WangGaoyi Yang
Research 22 April 2026
Article: 342
Part of 1 collection:Amyotrophic lateral sclerosis: latest advances and novel updates
所属专题合集：肌萎缩侧索硬化症：最新进展与更新
Duration of anti-seizure medicines started for acute symptomatic seizures due to acute meningitis: a systematic review and meta-analysis
急性脑膜炎所致急性症状性发作的抗癫痫药物起始疗程：一项系统综述与荟萃分析
Manya PrasadAmit KumarTarun Dua
Research 22 April 2026
Article: 341
Part of 1 collection:Acute meningitis: a collection of systematic reviews
所属专题合集：急性脑膜炎：系统综述集
Prenatal exposure to flood and risk of low birth weight: a multi-country study from 36 African countries
产前遭遇洪水与低出生体重风险：来自36个非洲国家的多国研究
Qian LiQian LiFengchao Liang
Research 21 April 2026
Article: 340
Part of 1 collection:Climate change and human health
所属专题合集：气候变化与人类健康
Sunshine duration and episodes of mental disorders and the inverse effect modification by ambient temperature
日照时长与精神障碍发作及环境温度的逆效应修饰
Lijun BaiJuan ChenShaowei Wu
Research 21 April 2026
Article: 339
The role of continuous glucose monitoring for diagnosis of gestational diabetes: exploring the potential
持续葡萄糖监测在妊娠糖尿病诊断中的作用：潜力探索
M. CrowleyC. NewmanF. P. Dunne
Review 21 April 2026
Article: 338
Part of 1 collection:Diagnosis and management of gestational diabetes
所属专题合集：妊娠糖尿病的诊断与治疗
Pre-diagnostic biomarkers and risk of stress-related disorders: a cohort study based on electronic health records
应激相关障碍诊断前生物标志物与风险：一项基于电子健康记录的队列
Anna A. PeltolaEsha KhanJake Lin
Research 01 June 2026
Article: 337
Epigenome-wide analysis of DNA-methylation signatures following climate-related disasters
气候相关灾害后DNA甲基化信号的全表观基因组分析
Wenzhong HuangRongbin XuYuming Guo
Research 20 April 2026
Article: 336
Part of 1 collection:Climate change and human health
所属专题合集：其后变化与人类健康
Redeemed prescription medicines to measure quality of life of patients with long-term conditions: a national cross-sectional study
通过已兑换的处方药衡量慢性病患者生活质量：一项全国性横断面研究
Henrik Hedegaard Pliess LarsenVolkert SiersmaAnne Holm
Research 20 April 2026
Article: 335
Part of 1 collection:Healthy aging and longevity: the role of preventive medicine and risk factors
属于专题合集：健康老龄化与长寿：预防医学和风险因素的作用
Viral shedding dynamics in coxsackievirus A6 hand, foot, and mouth disease: a prospective, individual-level analysis
柯萨奇病毒A6型手足口病的病毒排毒动态：一项前瞻性个体水平分析
Jiale MengYue ChengLu Long
Research 18 April 2026
Article: 334
Mental health and wellbeing interventions for uniformed service personnel: a mixed methods systematic review
军警人员心理健康与福祉干预措施：一项混合方法系统综述
Jessica EatonHolly EllardAlan Simpson
Research 17 April 2026
Article: 333
WISE-Therapy (What’s Important: Schedule and Engage) and bouldering psychotherapy for depression: A randomized clinical trial
WISE-Therapy（智慧疗法）（重要之事：安排与参与）与抱石心理治疗用于抑郁症：一项随机临床试验
Johannes KornhuberPiotr LewczukKatharina Luttenberger
Research 27 May 2026
Article: 332
Handgrip weakness is associated with motor cortex atrophy in rheumatoid arthritis: a cross-sectional study with a hand exercise intervention
握力减弱与类风湿关节炎患者运动皮层萎缩相关：一项包含手部运动干预的横断面研究
Amanda L GustafssonRolf A HeckemannCaroline Wasén
Research 26 May 2026
Article: 331
Interpretable multimodal PET/CT-EHR fusion via mixture-of-experts for prognostic stratification in mantle cell lymphoma: a multicenter study
基于专家混合模型的可解释性多模态PET/CT-HER（电子健康记录）融合在套细胞淋巴瘤预后分层中的应用：一项多中心研究
Chong JiangZitong ZhangRong Tian
Research 16 April 2026
Article: 330
Non-invasive diagnosis strategy integrating PSMA PET/CT and mpMRI for patients with suspected prostate cancer: a multi-center study
整合PSMA PET/CT与多参数MRI的无创诊断策略用于疑似前列腺癌患者：一项多中心研究
Yuhang WangYongxiang TangYi Cai
Research 16 April 2026
Article: 329
Clinical benefit of tenecteplase despite failed recanalization in late-window ischemic stroke: a post hoc analysis of the TRACE-3 trial
晚期窗口缺血性卒中中即使再通失败，替奈普酶仍具临床获益：TRACE-3试验的事后分析
Zhengzhao LuZiran WangYongjun Wang
Research 16 April 2026
Article: 328
Infant subcortical brain volumes associated with maternal obesity and diabetes: a large multicohort human study
婴儿皮层下脑容量与母亲肥胖及糖尿病相关：一项大型多队列人类研究
Ann M. AlexJerod M. RasmussenENIGMA-ORIGINs working group
Research 16 April 2026
Article: 327
Cost-effectiveness of prehabilitation for elderly (pre-)frail patients prior to elective surgery compared to standard care - an economic evaluation from a societal perspective
择期手术前老年（衰弱前期/）衰弱患者预康复与标准护理的成本效益比较——一项基于社会视角的经济学评估
Tanja RombeyHelene EckhardtLukas Schöner
Research 21 May 2026
Article: 326
Frozen melanoma tissues yield extracellular vesicles with preserved diagnostic and immunogenic properties
冷冻黑色素瘤组织可获得具有保存完好的诊断和免疫特性的细胞外囊泡
Daniele D´ArrigoKyong-Su ParkRossella Crescitelli
Research 21 May 2026
Article: 325
Mechanisms underlying immunodynamics of layered defenses elicited by mRNA vaccination in children
儿童mRNA疫苗接种所引发的分层防御免疫动力学的潜在机制
Yiyu LiaoHoong Kai ChuaKeisuke Ejima
Research 15 April 2026
Article: 324
Epigenetic aging markers in the association between frailty and mortality among U.S. adults
美国成年人虚弱与死亡率相关性中的表观遗传衰老标志物
May A. BeydounNicole Noren HootenAlan B. Zonderman
Research 15 April 2026
Article: 323
Part of 1 collection:Healthy aging and longevity: the role of preventive medicine and risk factors
所属专题合集：健康老龄化与长寿：预防医学和风险因素的作用
Evolution with age of the relationship between sex and post-COVID symptoms: a population-based cohort study
性别与新冠后遗症症状关系随年龄的演变：一项基于人群的队列研究
Anne PastorelloCécile Vuillermozfor the EpiCov study group
Research 14 April 2026
Article: 322
Bowel cancer care in individuals with an intellectual disability: a population-based cohort study of symptoms, diagnostic pathways, treatment and survival
智力障碍个体的肠癌护理：症状、诊断路径、治疗及生存的基于人群的队列研究
Oliver John KennedyUmesh ChauhanDarren Mark Ashcroft
Research 20 May 2026
Article: 321
Association of antiviral use for influenza among non-severe cases with subsequent hospitalization and mortality
非重症流感病例使用抗病毒药物与后续住院及死亡的关系
Taito KitanoShinya TsuzukiSayaka Yoshida
Research 06 April 2026
Article: 320
Social and digital engagement associated with reduced depressive symptoms in adults aged 50 and older: a multi-country cohort study
社交及数字互动与50岁及以上成年人抑郁症状减少的关系：一项多国队列研究
Yaping WangLiyuan TaoJue Liu
Research 07 April 2026
Article: 319
Fat-soluble vitamin deficiency in children with neurodevelopmental disorders: a cross-sectional study
神经发育障碍儿童脂溶性维生素缺乏：一项横断面研究
Jingjing RaoXiaomei WangChangzhen Li
Research 08 April 2026
Article: 318
Part of 1 collection:Child and adolescent psychiatry
所属专题合集：儿童与青少年精神病学
Skeletal and cardiac muscle longitudinal associations in the Baltimore Longitudinal Study of Aging (BLSA)
巴尔的摩老龄化纵向研究（BLSA）中骨骼肌与心肌的纵向关联
Jie Jun WongFei GaoAngela S. Koh
Research 06 April 2026
Article: 317
Part of 1 collection:Healthy aging and longevity: the role of preventive medicine and risk factors
所属专题合集：健康老龄化与长寿：预防医学与风险因素的作用
Early repetitive transcranial magnetic stimulation for preventing chronic postoperative pain in older adults: a randomized clinical sub-study
早期重复经颅磁刺激预防老年患者慢性术后疼痛：一项随机临床子研究
Wei-Wei ZhouZhi YangChao-Chao Zhong
Research 06 April 2026
Article: 316
Part of 1 collection:Neuromodulation in brain functional disorders
所属专题合集：脑功能障碍中的神经调控
Clinical epidemiology and risk prediction of unsuccessful treatment outcomes in pulmonary tuberculosis with diabetes mellitus
合并糖尿病的肺结核治疗失败结局的临床流行病学与风险预测
Ping LiFeilong LuJunjun Jiang
Research 25 March 2026
Article: 315
Part of 1 collection:Diabetes and infectious disease
所属专题合集：糖尿病与感染性疾病
Spatiotemporal patterns of climate-sensitive vector-borne diseases in Bangladesh: leveraging machine learning and spatial regression for intervention strategies
孟加拉国气候敏感型虫媒传染病的时空格局：利用机器学习与空间回归制定干预策略
Md. Siddikur RahmanMd. Abu Bokkor ShiddikArman Hossain Chowdhury
Research 13 April 2026
Article: 314
Part of 1 collection:Climate change and human health
所属专题合集：气候变化与人类健康
The association of pregnancy complications/risk factors with the development of cancer in women: an umbrella review
妊娠并发症/危险因素与女性癌症发生的关系：一项伞状综述
Jemma HealeyMegha SinghMairead Black
Research 13 April 2026
Article: 313
Synergistic effects of obesity and type 2 diabetes on adiposity-related cancer risk across age strata
肥胖与2型糖尿病对不同年龄层肥胖相关癌症风险的协同效应
Alex E. HenneyMegan HeagueDaniel J. Cuthbertson
Research 13 April 2026
Article: 312
Acute COVID-19 severity and impaired cognitive function up to 32months after diagnosis: an observational study
急性新冠严重程度与确诊后长达32个月的认知功能损害：一项观察性研究
Ingibjörg MagnúsdóttirAnders B. NygaardUnnur Anna Valdimarsdóttir
Research 11 April 2026
Article: 311
Maternal macronutrient intake and gestational diabetes: systematic review of prospective observational studies and dose-response meta-analyses
孕产妇宏量营养素摄入与妊娠期糖尿病：前瞻性观察研究的系统综述及剂量反应荟萃分析
Cameron D. YoungMichael G. GarrattAndrew N. Reynolds
Research 11 April 2026
Article: 310
Part of 1 collection:Diagnosis and management of gestational diabetes
所属专题合集：妊娠期糖尿病的诊断与管理
Global, regional, and national burden of colorectal cancer attributable to central obesity: a population attributable fraction analysis
中心性肥胖所致结直肠癌的全球、区域及国家负担：人群归因分数分析
Daniele PiovaniGisella FiglioliStefanos Bonovas
Research 10 April 2026
Article: 309
Evaluating DNA methylation markers and extended HPV genotyping in first-void urine for detecting high-grade cervical lesions in HPV-positive women: a cross-sectional study
评估首段尿液中DNA甲基化标志物及扩展型HPV基因分型在HPV阳性女性中检测高级别宫颈病变的价值：一项横断面研究
Mette TranbergSeverien Van KeerRenske Steenbergen
Research 10 April 2026
Article: 308
Targeted long-read genomic and epigenomic profiling enhances timely comprehensive variant discovery in hypotonia and muscle weakness
靶向长读长基因组与表观基因组测序提升低张力与肌无力的全面变异及时发现
Eman AbuijlanShruti SinhaAhmad Abou Tayoun
Research 08 April 2026
Article: 307
Targeting immunosenescence in lung diseases: mechanistic insights and clinical interventions
靶向肺疾病中的免疫衰老：机制洞察与临床干预
Yin ZhangXianzhe YuFengming Luo
Review 08 April 2026
Article: 306
Apolipoprotein C3 drives adverse cardiac remodeling in ischemic heart failure
载脂蛋白C3促进缺血性心力衰竭中的不良心脏重塑
Yufei HanYixue ZhaoXunde Xian
Research 09 April 2026
Article: 305
Part of 1 collection:Cardiac immunity and inflammation
所属专题合集：心脏免疫与炎症
Causal modeling of school aversion in psychiatrically referred adolescents: a DoWhy-based analysis
转诊精神病科的青少年厌学情绪的因果模型：基于DoWhy的分析
Mengmeng ZhangXin MaMeijuan Wang
Research 09 April 2026
Article: 304
Part of 1 collection:Child and adolescent psychiatry
所属专题合集：儿童与青少年精神病学
Aperiodic and periodic neural activity during sleep in autism spectrum disorders
自闭症谱系障碍睡眠中的非周期性和周期性神经活动
Noemi MazzoniEva-Maria KurzAndrea Caria
Research 18 March 2026
Article: 303
Part of 1 collection:Sleep and mental health
所属专题合集：睡眠与心理健康
Association and mediating pathways between intergenerational educational mobility and depressive symptoms: findings from high- and middle-income countries
代际教育流动性与抑郁症状之间的关联及中介路径：来自高收入和中等收入国家的发现
Yingchao ZengSimu HuangChihua Li
Research 02 April 2026
Article: 302
Part of 1 collection:Healthy aging and longevity: the role of preventive medicine and risk factors
所属专题合集：健康老龄化与长寿：预防医学和风险因素的作用
Scoping review on the prioritisation of high-consequence infectious pathogens for research preparedness and response to health emergencies
关于优先研究高后果性感染病原体以应对突发卫生事件的研究准备与响应的范围综述
Nicolas PulikHolly SadlerAlice Norton
Research 01 April 2026
Article: 301
Serum uric acid levels among children and adolescents in China: percentile reference values and national prevalence estimates of hyperuricemia
中国儿童和青少年血清尿酸水平：高尿酸血症的百分位参考值和全国患病率估计
Qianrang ZhuXin’nan ZongMin Zhao
Research 31 March 2026
Article: 300
Waist circumference and grip strength and their joint relations to type 2 diabetes incidence in UK Biobank
腰围和握力及其与英国生物银行中2型糖尿病发病风险的联合关系
Johanna WirlerMichael J. SteinMichael F. Leitzmann
Research 07 May 2026
Article: 299
Part of 1 collection:Healthy aging and longevity: the role of preventive medicine and risk factors
所属专题合集：健康老龄化与长寿：预防医学和风险因素的作用
Targeting cardiomyocyte-derived extracellular vesicle miR-574-5p protects against cognitive impairment induced by ischemia–reperfusion
靶向心肌细胞衍生的外泌体miR-574-5p可预防缺血再灌注引起的认知障碍
Erya ChenXiaoyu ZhuChan Chen
Research 19 March 2026
Article: 298
Motor-related reorganization in left inferior frontal gyrus after subcortical stroke: neurochemical basis and response to targeted neuromodulation
皮层下卒中后左侧额下回的运动相关重组：神经化学基础及靶向神经调控的反应
Wenjun HongYaxi WangZhiyong Zhao
Research 27 March 2026
Article: 297
Part of 1 collection:Neuromodulation in brain functional disorders
所属专题合集：脑功能疾病中的神经调控
Association between ambient temperature and childhood vaccination coverage in low- and middle-income countries
中低收入国家环境温度与儿童疫苗接种覆盖率之间的关联
Hongqiu ZhengYixiang ZhuZhiyuan Hou
Research 11 March 2026
Article: 296
Part of 1 collection:Climate change and human health
所属专题合集：气候变化与人类健康
White matter changes in reward circuits of amyotrophic lateral sclerosis: a fixel-based study of appetite loss
肌萎缩侧索硬化症奖赏回路白质改变：基于纤维束的食欲减退研究
Jeryn ChangHarry LipscombeThomas B. Shaw
Research 27 March 2026
Article: 295
Part of 1 collection:Amyotrophic lateral sclerosis: latest advances and novel updates
所属专题合集：肌萎缩侧索硬化症：最新进展与新动态
The adverse effects associated with tirzepatide use in patients at increased risk of cardiovascular events: a systematic review with meta-analysis and Trial Sequential Analysis
替西帕肽在心血管事件风险增加患者中的不良反应：一项系统综述与荟萃分析及试验序贯分析
Christina Dam Bjerregaard SillassenPascal FaltermeierJanus Christian Jakobsen
Research 27 March 2026
Article: 294
Part of 1 collection:Weight loss interventions and their health impacts
所属专题合集：减肥干预措施及其健康影响
Age-related genomic characterization and therapeutic targets in Chinese breast cancer: insights from prospective targeted sequencing and clinical data analysis
中国乳腺癌年龄相关基因组特征及治疗靶点：前瞻性靶向测序与临床数据分析的见解
Xin-Yi SuiXiao-Qing SongLei Fan
Research 27 March 2026
Article: 293
Impact of the family cohesion-centered frailty intervention on older gastric cancer patients: a non-randomized controlled trial
以家庭凝聚力为中心的衰弱干预对老年胃癌患者的影响：一项非随机对照试验
Yinning GuoYimeng ChenQin Xu
Research 27 March 2026
Article: 292
Part of 1 collection:Clinical trials for gastrointestinal cancer
所属专题合集：胃肠道癌症临床试验
Perceptions of HPV vaccination: a qualitative study with adolescents, parents, school staff, and pharmacists
对HPV疫苗接种的看法：一项针对青少年、家长、学校工作人员和药剂师的定性研究
Laurène HoutinLucia RomoClémence Brun
Research 26 March 2026
Article: 291
Risk classification of internet gaming disorder based on neurobiological subtyping from impulsivity-linked resting-state functional connectivity: a longitudinal design study
基于冲动性相关静息态功能连接神经生物学亚型的网络游戏障碍风险分类：一项纵向设计研究
Xinwen WenJiahao ZhaoKai Yuan
Research 26 March 2026
Article: 290
Part of 1 collection:Child and adolescent psychiatry
所属专题合集：儿童与青少年精神病学
Trainee-delivered school-based intervention with guided narrative writing for adolescent anxiety and depression: a cluster randomized controlled trial
由受训者实施的、基于学校的、以引导性叙事写作为干预手段的青少年焦虑和抑郁干预：一项整群随机对照试验
Yixuan WangMuyang LiYinyin Zang
Research 26 March 2026
Article: 289
Part of 1 collection:Child and adolescent psychiatry
所属专题合集：儿童与青少年精神病学
Nourishing future generations: the critical role of healthy school lunches and strategic food procurement
滋养未来一代：健康学校午餐和战略性食品采购的关键作用
Aurora Perez-CornagoCarmen Piernas
Comment 05 May 2026
Article: 288
Multi-omics analysis reveals sex-specific etiology of human muscle weakness following musculoskeletal injury
多组学分析揭示人类骨骼肌损伤后肌无力的性别特异性病因
Alexander R. KeebleAllison M. OwenChristopher S. Fry
Research 26 March 2026
Article: 287
Public health impact of catch-up vaccination or additional booster doses with pre-erythrocytic malaria vaccine R21/Matrix-M: a modelling study
使用红细胞前期疟疾疫苗R21/Matrix-M进行追赶接种或额外加强接种的公共卫生影响：一项建模研究
Kelly McCainHillary M. TopazianAzra C. Ghani
Research 25 March 2026
Article: 286
A digital-health multidomain lifestyle management framework and its associations with cardiometabolic health: a real-world observational study
数字健康多领域生活方式管理框架及其与心脏代谢健康的关联：一项现实观察性研究
Han XiaoKexin DingDafang Chen
Research 25 March 2026
Article: 285
Bilateral sequential accelerated theta-burst stimulation for treatment-resistant depression: an open-label randomized controlled trial
双侧序贯加速θ波爆发刺激治疗难治性抑郁症：一项开放标签随机对照试验
Xingxing LiEnze TangDongsheng Zhou
Research 25 March 2026
Article: 284
Part of 1 collection:Neuromodulation in brain functional disorders
所属专题合集：脑功能疾病中的神经调控
Digenic inheritance of mutations in SPG7 and AFG3L2 causes motor neuron and cerebellar disorders
SPG7和AFG3L2基因突变双基因遗传导致运动神经元和小脑疾病
Mehrdad A. EstiarEric YuZiv Gan-Or
Research 24 March 2026
Article: 283
Part of 1 collection:Amyotrophic lateral sclerosis: latest advances and novel updates
所属专题合集：肌萎缩侧索硬化症：最新进展与新颖动态
Social isolation and 59 common health conditions: insights from observational and genetics analyses
社交孤立与59种常见健康状况：观察性研究与遗传学分析的见解
Sizhi AiQiqi WuYannis Yan Liang
Research 23 March 2026
Article: 282
Clustering depression subgroups based on dorsolateral prefrontal-subgenual anterior cingulate cortex peak functional connectivity reveals different symptom profiles and TMS treatment outcomes
基于背外侧前额叶-膝下前扣带回皮层峰值功能连接性的抑郁亚组聚类分析揭示了不同的症状特征和经颅磁刺激（TMS）治疗结果
Gai KongSirui WangYingying Tang
Research 23 March 2026
Article: 281
Robust human genetic evidence supporting causal effects of FGF21 on reducing alcohol consuming behaviours
人类遗传学有力证据支持成纤维细胞生长因子21（FGF21）对减少饮酒行为的因果效应
Héléne T. CronjéSile HuDipender Gill
Research 23 March 2026
Article: 280
Artificial intelligence-based prediction of fetal hypoxia: a multicenter model development and nationwide AI-human comparison
基于人工智能的胎儿缺氧预测：多中心模型开发及全国范围的人工智能与人类对比
Suiwen LinXiaodan DiBin Liu
Research 21 March 2026
Article: 279
Efficacy and long-term engagement of a WeChat-integrated modality versus a traditional quitline on smoking cessation in China: a randomised controlled trial
微信整合模式与传统戒烟热线在中国戒烟中的疗效及长期参与度：一项随机对照试验
Shuilian ChuDi ZhangLirong Liang
Research 21 March 2026
Article: 278
A culturally-safe primary care intervention for migrant/refugee women suffering domestic violence and abuse: HARMONY—a pragmatic cluster randomised controlled trial
针对遭受家庭暴力和虐待的移民/难民妇女的文化安全初级护理干预措施：HARMONY——一项实用性整群随机对照试验
Angela J. TaftFelicity YoungGene Feder
Research 21 March 2026
Article: 277
Development, integration, retention, and career progression of physician associates/assistants in UK NHS hospitals and clinical teams: a multiple-case qualitative study
英国国家医疗服务体系（NHS）医院及临床团队中医师助理/协理医师的发展、整合、留任及职业晋升：一项多案例定性研究
Yingxi ZhaoRhys SwainstonThe ROADMAP-PA collaborator group
Research 20 April 2026
Article: 276
Compound climate extreme events and associated health impacts: a scoping review
复合气候极端事件及其相关健康影响：一项范围性综述
Shifali MathewsCaitlin WalkerJaime Madrigano
Research 20 March 2026
Article: 275
Part of 1 collection:Climate change and human health
所属专题合集：气候变化与人类健康
Smoking history, eligibility for lung cancer screening and risk of death by lung cancer or other causes -- a longitudinal, time-variable analysis of the EPIC-Heidelberg cohort
吸烟史、肺癌筛查资格以及死于肺癌或其他原因的风险——对EPIC-海德堡队列的纵向、时变分析
Yue ChenSrimanti DuttaRudolf Kaaks
Research 28 April 2026
Article: 274
Part of 1 collection:Healthy aging and longevity: the role of preventive medicine and risk factors
所属专题合集：健康老龄化与长寿：预防医学和风险因素的作用
Cortical functional hierarchy disruption following subcortical stroke
皮质功能层级在皮层下卒中后的破坏
Ke WuGang LiuGaolang Gong
Research 19 March 2026
Article: 273
Characterizing the effects of genetic liability to autoimmune conditions on pregnancy outcomes using Mendelian randomization
利用孟德尔随机化方法表征遗传易感性对自身免疫性疾病患者妊娠结局的影响
Elisabeth AitonNancy S. McBrideMaria Carolina Borges
Research 19 March 2026
Article: 272
Dystrophin-gene mutation location influences severity of electroretinogram defects in mouse models of Duchenne muscular dystrophy
杜氏肌营养不良症小鼠模型中，肌营养不良蛋白基因突变位置对视网膜电图缺陷严重程度的影响
André Maurício Passos LiberMirella BarboniCyrille Vaillend
Research 25 April 2026
Article: 271
Personalizing the treatment of head and neck cancer in vitro: The 3D-OTC model
体外个性化治疗头颈部肿瘤：三维器官芯片（3D-OTC）模型
Fabian StögbauerTobias WeiserBarbara Wollenberg
Research 25 April 2026
Article: 270
Part of 1 collection:Organoids: connecting molecular insights and clinical practice
所属专题合集：类器官：连接分子见解与临床实践
Risk factor profiles for infections in individuals with type 2 diabetes: a prospective cohort study
2型糖尿病患者感染的风险因素特征：一项前瞻性队列研究
Han-Cheng YuJi-Juan ZhangYun-Fei Liao
Research 18 March 2026
Article: 269
Part of 1 collection:Diabetes and infectious disease
所属专题合集：糖尿病与感染性疾病
Cause-specific years of life lost attributable to non-optimal body mass index by county, sex, race, and ethnicity in the USA, 2000–2019: a systematic analysis of health disparities
2000-2019年美国按县、性别、种族和民族划分的非最佳体重指数导致的特定原因寿命损失年数：一项关于健康差异的系统分析
GBD US Health Disparities CollaboratorsFarah MouhannaLaura Dwyer-Lindgren
Research 18 March 2026
Article: 268
Global and regional prevalence, burden, and risk factors for MASLD in children and adolescents aged 5 to 24years: a systematic review, meta-analysis, and modeling study
全球和区域5至24岁儿童和青少年代谢相关脂肪性肝病（MASLD）的患病率、负担及风险因素：一项系统综述、荟萃分析和建模研究
Yunfei LiuShan CaiSusan M. Sawyer
Research 18 March 2026
Article: 267
Relative leukocyte telomere length and the risk of lung cancer progression in individuals with pulmonary nodules
相对白细胞端粒长度与肺结节患者肺癌进展风险的关系
Yuanyuan WuDong SunFeifei Cheng
Research 18 March 2026
Article: 266
Effects of Tai Chi combined with transcranial direct current stimulation on pain in knee osteoarthritis: a randomized controlled neuroimaging trial
太极拳结合经颅直流电刺激对膝骨关节炎疼痛的影响：一项随机对照神经影像学试验
Xuefeng LiuTong TangJing Tao
Research 17 March 2026
Article: 265
DNA hypermethylation of choline kinases drives blockage of choline-phosphatidylcholine biosynthesis: lipidomic biomarkers and epigenetic insights of hepatic steatosis induced by arsenic
胆碱激酶DNA高甲基化驱动胆碱-磷脂酰胆碱生物合成受阻：砷诱导的肝脂肪变性的脂质组学生物标志物及表观遗传学见解
Qiwen FuQi WangLu Ma
Research 17 March 2026
Article: 264
Dynamics of Mpox epidemics by the interplay of COVID-19 pandemic in Africa
非洲猴痘（Mpox）流行与新冠肺炎（COVID-19）大流行相互作用下的猴痘流行病学动态
Oyewole K. OyedeleNifarta P. AndrewAlash’le Abimiku
Research 17 March 2026
Article: 263
Part of 1 collection:Mpox: Epidemiology, prevention, and treatment
所属专题合集：猴痘：流行病学、预防和治疗
SPP1high fibrogenic macrophages mediate protective fibrotic remodeling and promote vascular stability in hypertension-associated aortic dissection
SPP1高表达成纤维性巨噬细胞介导保护性纤维化重塑并促进高血压相关主动脉夹层的血管稳定性
Shuai ZhaoXiumeng HuaJiangping Song
Research 16 March 2026
Article: 262
Longitudinal associations between body fat mass and cardiovascular outcomes among Chinese children: mediation by cardiometabolic risk factors
中国儿童身体脂肪量与心血管结局之间的纵向关联：通过心脏代谢风险因素的中介作用
Hui YangQin LiuBo Xi
Research 16 March 2026
Article: 261
The timing of the commencement of pulmonary rehabilitation in hospitalized patients with acute exacerbation of COPD: a systematic review and network meta-analysis
住院慢性阻塞性肺疾病急性加重患者开始肺康复治疗的时机：一项系统综述和网络荟萃分析
Peilin JiaHailong ZhangLongyu Wang
Research 16 March 2026
Article: 260
Correction: Vegetable intake and the risk of bladder cancer in the BLadder Cancer Epidemiology and Nutritional Determinants (BLEND) international study
更正：膀胱癌流行病学和营养决定因素（BLEND）国际研究中蔬菜摄入量与膀胱癌风险的关系
Evan Yi-Wen YuAnke WesseliusMaurice P. Zeegers
Correction 22 April 2026
Article: 259
Comparative efficacy of neoadjuvant short-course versus long-course radiotherapy-based regimens with or without immunotherapy for locally advanced pMMR rectal cancer: a systematic review and network meta-analysis
基于放疗的新辅助短疗程与长疗程治疗方案（联合或不联合免疫治疗）对局部晚期错配修复功能正常（pMMR）型直肠癌的疗效比较：一项系统综述与网状荟萃分析
Liqing LiXiaoyao MengTingshi Su
Research 14 March 2026
Article: 258
Association between bariatric surgery and long-term ability to perform household tasks in the Swedish Obese Subjects study: a controlled prospective cohort study
瑞典肥胖受试者研究：减肥手术与长期从事家务能力之间的关联——一项对照前瞻性队列研究
Petra BrembeckJohanna C. Andersson-AssarssonPer-Arne Svensson
Research 18 April 2026
Article: 257
Part of 1 collection:Weight loss interventions and their health impacts
所属专题合集：减重干预措施及其健康影响
The role of male foetal sex on maternal and neonatal outcomes in pregnancies complicated by gestational diabetes—secondary analysis of a randomised placebo controlled clinical trial of metformin in gestational diabetes (EMERGE)
男性胎儿性别对妊娠期糖尿病合并妊娠的母婴预后的影响——妊娠期糖尿病二甲双胍随机对照安慰剂临床试验（EMERGE）的二次分析
Christine NewmanAlberto Alvarez-IglesiasFidelma Dunne
Research 12 March 2026
Article: 256
Part of 1 collection:Diagnosis and management of gestational diabetes
所属专题合集：妊娠期糖尿病的诊断与管理
Downregulated lysyl oxidase in plasma extracellular vesicles: a biomarker linked to brain metastasis risk in lung adenocarcinoma
血浆细胞外囊泡中赖氨酰氧化酶表达下调：与肺腺癌脑转移风险相关的生物标志物
Jing LiYu PeiYi Liu
Research 12 March 2026
Article: 255
The influence of age-dependent susceptibility on RSV transmission dynamics and immunisation population-level impact
年龄依赖性易感性对呼吸道合胞病毒（RSV）传播动力学及免疫接种人群层面影响的研究
Chenkai ZhaoYuhe ZhangHarish Nair
Research 11 March 2026
Article: 254
A human-derived Bacteroides strain attenuates depressive-like behavior in a rat model of social defeat-induced stress
一株人源拟杆菌属菌株可减轻社会挫败诱导应激大鼠模型的抑郁样行为
Marisol I. DothardMariaelena CaboniPhilip Strandwitz
Research 10 March 2026
Article: 253
Adverse events in both childhood and adulthood are associated with molecular, clinical and functional markers of ageing
童年和成年期的不良事件均与衰老的分子、临床和功能标志物相关
Monica AasThole H HoppenJulian Mutz
Research 28 April 2026
Article: 252
Part of 1 collection:Healthy aging and longevity: the role of preventive medicine and risk factors
所属专题合集：健康老龄化与长寿：预防医学和风险因素的作用
Genetic predisposition to high BMI, ultra-processed food consumptions in childhood, and adiposity in young adulthood: a 17-year prospective cohort study of 3061 individuals
高BMI遗传易感性、儿童期超加工食品摄入与成年早期肥胖：一项对3061例个体进行的为期17年的前瞻性队列研究
Ziyi ZhouQiaosen ChenFrederick K. Ho
Research 16 April 2026
Article: 251
Enhanced predictive performance of artificial intelligence in individualized ovarian stimulation of in vitro fertilization: a retrospective cohort study
人工智能在体外受精个体化卵巢刺激中的预测性能提升：一项回顾性队列研究
Guiquan WangMinyue TangYimin Zhu
Research 10 March 2026
Article: 250
PCDSOS: a novel clinical predictive tool for screening primary ciliary dyskinesia in adult bronchiectasis patients—a multicenter derivation and external validation study
PCDSOS：一种用于筛查成人支气管扩张症患者原发性纤毛运动障碍的新型临床预测工具——一项多中心推导及外部验证研究
Wangji ZhouLin WangXinlun Tian
Research 10 March 2026
Article: 249
Detection rate and mutational landscape in extracranial arteriovenous malformations: a cohort study
颅外动静脉畸形的检出率及突变谱：一项队列研究
Vanessa F. SchmidtDenny Schanzefor the APOLLON Investigators
Research 16 April 2026
Article: 248
Kinetics of antibodies and risk of respiratory syncytial virus infection: a longitudinal cohort in Taizhou City, eastern China
抗体动力学与呼吸道合胞病毒感染风险：中国东部台州市的一项纵向队列研究
Qiang WangDavid HodgsonWeibing Wang
Research 09 March 2026
Article: 247
Cell therapy strategies for organ regeneration
器官再生的细胞治疗策略
L. PapamichailL. J. W. van der LaanM. J. Hoogduijn
Review 25 February 2026
Article: 246
Transcutaneous spinal cord stimulation combined with robot-assisted gait training to improve mobility and balance in spinal cord injury: intramuscular electromyography as a biomarker for functional recovery
经皮脊髓电刺激联合机器人辅助步态训练改善脊髓损伤患者的行动能力和平衡能力：肌内肌电图作为功能恢复的生物标志物
Abdul RashadHe XijingMuhammad Asif
Registered Report 09 March 2026
Article: 245
Neoadjuvant camrelizumab combined with radiotherapy as a chemotherapy-sparing approach for resectable locally advanced esophageal squamous cell carcinoma: a phase II clinical trial (ESOCORT-NIRT)
新辅助卡瑞利珠单抗联合放疗作为可切除局部晚期食管鳞癌的免化疗方案：一项II期临床试验（ESOCORT-NIRT）
Maohui ChenYizhou HuangBin Zheng
Research 09 March 2026
Article: 244
FLASH radiotherapy preserves systemic and tissue homeostasis while maintaining antitumor efficacy
FLASH放疗在保持抗肿瘤疗效的同时维持全身及组织稳态
Giulia FuriniEduarda Mota da SilvaMargherita Maffei
Research 26 February 2026
Article: 243
fMRI-guided V1-targeted rTMS improves depressive symptoms in adolescents and young adults with bipolar disorder: a double-blind randomized controlled trial
功能磁共振成像引导的V1区靶向重复经颅磁刺激改善青少年及青年双相情感障碍患者的抑郁症状：一项双盲随机对照试验
Xudong ZhaoHetong ZhouMinmin Wang
Research 07 March 2026
Article: 242
Part of 1 collection:Child and adolescent psychiatry
所属专题合集：儿童及青少年精神病学
Impairment of brain short association fibers across clinical stages in amyotrophic lateral sclerosis: a new biomarker mirroring disease progression
肌萎缩侧索硬化症临床各阶段脑短联结纤维受损情况：一种反映疾病进展的新型生物标志物
Nao-Xin HuangZi-Wei CaiHua-Jun Chen
Research 06 March 2026
Article: 241
Part of 1 collection:Amyotrophic lateral sclerosis: latest advances and novel updates
所属专题合集：肌萎缩侧索硬化症：最新进展与新动态
Social frailty and the risk of progression from health to physical, psychological, and cognitive multimorbidity: a prospective multi-cohort study
社会脆弱性与从健康状态进展至身体、心理及认知多病共存状态的风险：一项前瞻性多队列研究
Yaguan ZhouHtet Lin HtunYi Guo
Research 06 March 2026
Article: 240
Part of 1 collection:Healthy aging and longevity: the role of preventive medicine and risk factors
所属专题合集：健康老龄化与长寿：预防医学及风险因素的作用
Association between early life constituent-specific PM2.5 exposure and child development and the moderating role of greenness: a nationwide study in China
中国全国范围内早期生命特定成分PM2.5暴露与儿童发育的关联及绿地调节作用的研究
Ruili LiXiaoguo ZhengXiaoning Lei
Research 06 March 2026
Article: 239
Part of 1 collection:Child and adolescent psychiatry
所属专题合集：儿童及青少年精神病学
Intravenous thrombolysis versus standard medical therapy in minor stroke patients with large vessel severe stenosis or occlusion: a systematic review and meta-analysis
静脉溶栓与标准药物治疗轻型卒中合并大血管重度狭窄或闭塞患者的系统综述与荟萃分析
Tianhao ZhangLin TongZhigang Liang
Research 06 March 2026
Article: 238
Long-term risk of offspring type 1 and type 2 diabetes following maternal gestational diabetes mellitus: a nationwide birth cohort study with 10-year follow-up
母亲妊娠期糖尿病后子女患1型和2型糖尿病的长期风险：一项为期10年随访的全国出生队列研究
Joon Ho MoonHan Na JungSung Hee Choi
Research 06 March 2026
Article: 237
Part of 1 collection:Diagnosis and management of gestational diabetes
所属专题合集：妊娠期糖尿病的诊断与治疗
Parental income in childhood and health outcomes across age groups: a register-based study from Norway
童年期父母收入与各年龄段健康结局：一项基于挪威登记数据的研究
Bjørn-Atle RemeHans Fredrik SundeJonathan Wörn
Research 06 March 2026
Article: 236
AI-based quality control was associated with improved fetal ultrasound image quality in low-resource settings: a real-world multicenter study from West China
基于人工智能的质量控制可改善低资源环境下胎儿超声图像质量：一项来自中国西部的现实多中心研究
Jianxin ZhaoYao TangYong Huang
Research 06 March 2026
Article: 235
Reply to: Intraoperative use of sodium oxybate to prevent post-operative delirium in older patients undergoing major orthopedic surgery
回复：术中使用羟丁酸钠预防老年患者接受大骨科手术后谵妄
Meiying CuiHang XuePing Zhao
Matters Arising 13 April 2026
Article: 234
Hypothesis-free evaluation of circulating metabolome provides cell-specific insights regarding the role of energy substrate availability in amyotrophic lateral sclerosis
无假设的循环代谢组学评估为肌萎缩侧索硬化症中能量底物可用性的细胞特异性作用提供见解
Elham AlhathliJohnathan Cooper-KnockPamela J. Shaw
Research 06 March 2026
Article: 233
Part of 1 collection:Amyotrophic lateral sclerosis: latest advances and novel updates
所属专题合集：肌萎缩侧索硬化症：最新进展与新动态
Intraoperative use of sodium oxybate to prevent postoperative delirium in older patients undergoing major orthopedic surgery
术中使用羟丁酸钠预防老年患者接受大骨科手术后谵妄
Fu-Shan XueDan-Feng WangXiao-Chun Zheng
Matters Arising 13 April 2026
Article: 232
Statin therapy and stroke risk in patients with hypercholesterolaemia: a population-based longitudinal study using electronic health records in South London
他汀类药物治疗与高胆固醇血症患者卒中风险：一项基于南伦敦电子健康记录的纵向人群研究
Marc DelordAbdel Douiri
Research 05 March 2026
Article: 231
Thermal ablation versus hepatectomy for solitary colorectal liver metastases up to 5 cm: a multicenter target trial emulation on safety, efficacy, and cost-effectiveness
热消融与肝切除术治疗直径达5厘米的孤立性结直肠癌肝转移：一项关于安全性、疗效及成本效益的多中心目标试验模拟研究
Jianming LiLu LiPing Liang
Research 05 March 2026
Article: 230
Why hyperinsulinemia is detrimental to weight loss: insights from type 1 diabetes
为何高胰岛素血症不利于减重：来自1型糖尿病的见解
Stephan MartinKerstin KempfHubert Kolb
Debate 10 April 2026
Article: 229
Part of 1 collection:Weight loss interventions and their health impacts
所属专题合集：减重干预措施及其健康影响
Interventions to prevent and treat multiple long-term conditions and their consequences across the life course: concepts and definitions
预防和治疗多种长期疾病及其在生命周期中后果的干预措施：概念与定义
Miles D. WithamGuruprasad P. AithalThe Multiple Long-Term Conditions Cross-NIHR Collaboration Interventions and Prevention Workstream
Forum 10 April 2026
Article: 228
Effectiveness of nirmatrelvir/ritonavir and molnupiravir on post-COVID diabetes risk among an older adult cohort: a target trial emulation study
奈玛特韦/利托那韦和莫努匹韦对老年人群新冠后糖尿病风险的影响：一项目标试验模拟研究
Zihao GuoYuchen WeiKa Chun Chong
Research 17 March 2026
Article: 227
Part of 1 collection:Diabetes and infectious disease
所属专题合集：糖尿病与传染病
Iron deficiency and dementia risk: evidence from the Swedish population-based cohort study AMORIS
瑞典基于人群的队列研究AMORIS中铁缺乏与痴呆风险的证据
Mozhu DingAlexandra WennbergKarin Modig
Research 08 April 2026
Article: 226
Part of 1 collection:Healthy aging and longevity: the role of preventive medicine and risk factors
所属专题合集：健康老龄化与长寿：预防医学和风险因素的作用
Effects of ultrasound-guided stellate ganglion block in poststroke bulbar palsy: a double-blind placebo-controlled trial
超声引导下星状神经节阻滞对脑卒中后球麻痹的影响：一项双盲安慰剂对照试验
Hongji ZengWeihong ZhangXi Zeng
Research 04 March 2026
Article: 225
Dual-utility ctDNA in diffuse large B-cell lymphoma: integrated genotyping unveils minimal residual disease dynamics and subtype-specific clonal evolution
双用途循环肿瘤DNA在弥漫性大B细胞淋巴瘤中的应用：整合基因分型揭示微小残留病灶动态变化及亚型特异性克隆演变
Jin-Hua LiangYi-Fan WuWei Xu
Research 04 March 2026
Article: 224
Risks of non-breast, non-ovarian cancers for BRCA1 and BRCA2pathogenic variant carriers: a prospective cohort study
BRCA1和BRCA2致病性变异携带者患非乳腺、非卵巢癌的风险：一项前瞻性队列研究
Ruotong YangRobert J. MacInnisShuai Li
Research 04 March 2026
Article: 223
Cardiovascular outcomes of intensive blood pressure control in patients with and without metabolic dysfunction-associated fatty liver disease: post hoc analysis of the CRHCP trial
在伴有和不伴有代谢功能障碍相关脂肪性肝病的患者中，强化血压控制的心血管预后：CRHCP试验的事后分析
Songyue LiuYangzhi YinXiaofan Guo
Research 04 March 2026
Article: 222
The role of COPD and inhaled corticosteroids in major adverse cardiovascular events in cardiovascular-kidney-metabolic populations
慢性阻塞性肺疾病和吸入性糖皮质激素在心血管-肾脏-代谢人群主要不良心血管事件中的作用
Anne E. IoannidesEmily L. GraulJennifer K. Quint
Research 04 March 2026
Article: 221
Ethnic differences in the burden of cardiovascular disease risk factors among adult residents of London: the TOGETHER study
伦敦成年居民心血管疾病风险因素负担的种族差异：TOGETHER研究
Fotios BarkasMalo DirouKausik K. Ray
Research 03 March 2026
Article: 220
Development of a novel prognostic assessment tool for recurrent respiratory papillomatosis
复发性呼吸道乳头瘤病新型预后评估工具的开发
Satoshi YamadaTaro IkegamiKiyoshi Misawa
Research 16 April 2026
Article: 219
Response to: Matters Arising in relation to “Evaluating agreement between individual nutrition randomised controlled trials and cohort studies – a meta-epidemiological study”
针对“评估个体营养随机对照试验与队列研究之间的一致性——一项元流行病学研究”的相关问题探讨
Julia StadelmaierGina BantleLukas Schwingshackl
Matters Arising 09 April 2026
Article: 218
Concordance between nutritional cohorts and randomized trials: biological confirmation or statistical consequence? A re-analysis of Stadelmaier et al.
营养队列研究与随机试验之间的一致性：生物学证实还是统计学结果？对Stadelmaier等人的研究再分析
Matthew CalkinsIsaac NúñezAdrian Soto-Mota
Matters Arising 09 April 2026
Article: 217
Multimorbidity patterns and 15-year trajectories of physical performance: a population-based study
多病共存模式与15年身体机能变化轨迹：一项基于人群的研究
Francesco PalmeseDavide Liborio VetranoFederico Triolo
Research 25 March 2026
Article: 216
Part of 1 collection:Healthy aging and longevity: the role of preventive medicine and risk factors
所属专题合集：健康老龄化与长寿：预防医学和风险因素的作用
The need for clinical studies assessing whether weight loss improves functional outcome after stroke in diabetes
评估减肥是否改善糖尿病患者中风后功能预后的临床研究需求
Ellen VercalsterenMichael V. MazyaCesare Patrone
Debate 24 March 2026
Article: 215
Targeting STE20-type kinase MST3 improves metabolic dysfunction-associated steatohepatitis without affecting hepatocellular carcinoma development in mice
靶向STE20型激酶MST3可改善小鼠代谢功能障碍相关脂肪性肝炎，且不影响肝细胞癌的发展
Jingjing ZhangXiangdong GongyeMargit Mahlapuu
Research 24 March 2026
Article: 214
Multimorbidity patterns and the subsequent risk of albuminuria: findings from the Stockholm Creatinine Measurements (SCREAM) project
多病共存模式与后续白蛋白尿风险：来自斯德哥尔摩肌酐测量（SCREAM）项目的研究结果
Giorgi BeridzePatrick B. MarkJuan-Jesus Carrero
Research 24 March 2026
Article: 213
Myeloid-derived immunosuppression of chimeric antigen receptor T cells in the neuronal microenvironment of glioblastoma
胶质母细胞瘤神经元微环境中髓系来源的免疫抑制对嵌合抗原受体T细胞的影响
Junyi ZhangJasmin von EhrYahaya A. Yabo
Research 13 March 2026
Article: 212
Associations of genetically predicted interleukin-6 and tumor necrosis factor signaling pathways with mortality among persons with colorectal cancer: a two-sample Mendelian randomization
基因预测的白细胞介素-6和肿瘤坏死因子信号通路与结直肠癌患者死亡率之间的关联：一项双样本孟德尔随机化研究
Martina BoukaKatharina NimptschTobias Pischon
Research 06 March 2026
Article: 211
Disruption of the angiopoietin-like system connects lipid homeostasis and hypothalamic dysfunction in ALS
血管生成素样系统紊乱将肌萎缩侧索硬化症中的脂质稳态与下丘脑功能障碍关联起来
Sruthi Sankari KrishnamurthyAdriana Zardini BuzattoFrancesco Roselli
Research 03 March 2026
Article: 210
Part of 1 collection:Amyotrophic lateral sclerosis: latest advances and novel updates
所属专题合集：肌萎缩侧索硬化症：最新进展与新动态
Day+30 detection of minimal residual FLT3-ITD by high-sensitivity PCR-NGS predicts relapse risk and guides post-transplant maintenance in AML
移植后第30天通过高灵敏度PCR-NGS检测微小残留FLT3-ITD可预测急性髓系白血病（AML）复发风险并指导移植后维持治疗
Shan JiangDan FengErlie Jiang
Research 03 March 2026
Article: 209
Early childhood weight gain and alanine aminotransferase at age 8: an adjunct study of the Japan Environment and Children’s Study
幼儿期体重增长与8岁时丙氨酸氨基转移酶水平：日本环境与儿童研究的一项辅助研究
Naw Awn J-PKeiko YamasakiNarufumi Suganuma
Research 03 March 2026
Article: 208
Anti-CD19 chimeric antigen receptor T-cell therapy for relapsed or refractory Philadelphia chromosome-positive B cell acute lymphoblastic leukemia: a multicenter retrospective study
抗CD19嵌合抗原受体T细胞疗法治疗复发或难治性费城染色体阳性B细胞急性淋巴细胞白血病：一项多中心回顾性研究
Jinglei YuFengmei SongGuoqing Wei
Research 03 March 2026
Article: 207
Identification of cryosensitive niches and a targetable FOS/AP‑1 program in the human ovarian cortex by single‑cell and spatial transcriptomics
通过单细胞和空间转录组学鉴定人类卵巢皮质中的冷敏感生态位及可靶向的FOS/AP-1程序
Fanghao GuoDi SunWen Li
Research 03 March 2026
Article: 206
Neoadjuvant camrelizumab combined with metronomic chemotherapy in patients with advanced esophageal squamous cell carcinoma: a pilot randomized phase 2 trial
卡瑞利珠单抗联合节拍化疗新辅助治疗晚期食管鳞状细胞癌：一项随机2期初步试验
Zhiming ChenWenshuai LiJie Liu
Research 03 March 2026
Article: 205
Part of 1 collection:Clinical trials for gastrointestinal cancer
所属专题合集：胃肠道癌症临床试验
Vericiguat for endothelial dysfunction and CRT response in non-responders: the VERCET prospective observational study
维利西呱治疗无反应者的内皮功能障碍和心脏再同步化治疗（CRT）反应：VERCET前瞻性观察研究
Celestino SarduLudovica Vittoria MarfellaRaffaele Marfella
Research 03 March 2026
Article: 204
Part of 1 collection:Cardiomyopathy and cardiac arrhythmias
所属专题合集：心肌病和心律失常
Assessment of antibody responses to Anopheles SG6-P1 and Aedes N-term 34kDa salivary peptides: a randomised human-challenge trial of controlled exposures to vector bites
评估针对按蚊SG6-P1和伊蚊N端34 kDa唾液肽的抗体反应：一项对媒介叮咬进行可控暴露的随机人体挑战试验
Victor ChaumeauEllen A. KearneyFreya J. I. Fowkes
Research 02 March 2026
Article: 203
Is random biopsy necessary for normal esophageal mucosa during chromoendoscopy? Evidence from a population-based cohort study
在色素内镜检查过程中，对于正常食管黏膜是否有必要进行随机活检？一项基于人群的队列研究证据
Wenlei YangMengfei LiuYang Ke
Research 02 March 2026
Article: 202
Sinusoidal cell–derived biomarker scores predict diagnosis and prognosis in chronic liver disease
窦状隙细胞来源的生物标志物评分可预测慢性肝病的诊断和预后
Sergi Guixé-MuntetAnabel Fernández-IglesiasJordi Gracia-Sancho
Research 28 February 2026
Article: 201
Anticholinergic drug burden and incident cardiovascular events: a population-based study
抗胆碱能药物负担与新发心血管事件：一项基于人群的研究
Nanbo ZhuMaria EriksdotterHong Xu
Research 28 February 2026
Article: 200
Part of 1 collection:Healthy aging and longevity: the role of preventive medicine and risk factors
所属专题合集：健康老龄化与长寿：预防医学和风险因素的作用
Sensitive periods of BMI change from childhood to adulthood on subclinical cardiovascular outcomes: a 36-year prospective cohort study
从儿童期到成年期体重指数（BMI）变化对亚临床心血管结局影响的敏感期：一项为期36年的前瞻性队列研究
Hui YangTongshuai GuoJianjun Mu
Research 27 February 2026
Article: 199
Feasibility and preliminary efficacy of an art-making program to manage fear of cancer recurrence (AM-I-FCR) in lung cancer patients: a randomized controlled pilot study
艺术创作项目（AM-I-FCR）管理肺癌患者对癌症复发恐惧的可行性与初步疗效：一项随机对照试点研究
Jialing LinZhixuan KangFeifei Huang
Research 27 February 2026
Article: 198
Unveiling disparities in lung cancer care: a joint spatio-temporal analysis of multidisciplinary meeting presentation, supportive care screening, and diagnostic timeliness in Victoria
揭示肺癌诊疗差异：维多利亚州多学科会诊展示、支持性护理筛查及诊断及时性的联合时空分析
Getayeneh Antehunegn TesemaRob G. StirlingArul Earnest
Research 27 February 2026
Article: 197
Transcriptome-based high-frequency recurrence index predicts frequent recurrence in non-muscle-invasive bladder cancer after Bacillus Calmette-Guérin therapy
基于转录组的高频复发指数可预测卡介苗治疗后非肌层浸润性膀胱癌的频繁复发情况
Seung-Woo BaekYoung Joon ByunSeok Joong Yun
Research 27 February 2026
Article: 196
Life-course influence of birthweight and subsequent pathways on healthy aging: a Mendelian randomization study
出生体重对健康老龄化的终身影响及后续途径：一项孟德尔随机化研究
Lijie KongChun DouTiange Wang
Research 25 February 2026
Article: 195
Part of 1 collection:Healthy aging and longevity: the role of preventive medicine and risk factors
所属专题合集：健康老龄化与长寿：预防医学和风险因素的作用
Routine inflammatory indices modify clonal hematopoiesis-related prognostic risk in patients undergoing percutaneous coronary intervention: a real-world cohort study
常规炎症指标改变接受经皮冠状动脉介入治疗患者的克隆性造血相关预后风险：一项现实队列研究
Xuxiang ShenYing SongXiangfeng Lu
Research 25 February 2026
Article: 194
Health experiences and outcomes of autistic and non-autistic adults with hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorder
自闭症和非自闭症成年孤独症患者及非孤独症患者中患有高迁移率埃勒斯-丹洛斯综合征和高迁移率谱系障碍者的健康体验和预后
Catherine J. CromptonThemis N. EfthimiouKathryn M. Berg
Research 25 February 2026
Article: 193
Part of 1 collection:Child and adolescent psychiatry
所属专题合集：儿童与青少年精神病学
Effects of non-pharmacological interventions on sleep quality in older adults: a systematic review and network meta-analysis of randomized controlled trials
非药物干预措施对老年人睡眠质量影响：基于随机对照试验的系统综述和网络荟萃分析
Jia SongHeng DongShangfeng Tang
Research 25 February 2026
Article: 192
Cortical excitability mapping stratifies neurobiological subtypes of schizophrenia with genetic and molecular signatures
皮质兴奋性映射对具有遗传和分子特征的精神分裂症神经生物学亚型进行分层
Sixuan GuoYu ZhaoQiyong Gong
Research 25 February 2026
Article: 191
Minimum 18-week chemotherapy improves survival in locally advanced rectal cancer after neoadjuvant radiotherapy: a post hoc analysis of the STELLAR trial
新辅助放疗后局部晚期直肠癌患者接受至少18周化疗可改善生存率：STELLAR试验的事后分析
Tongzhen XuHuiying MaJing Jin
Research 25 February 2026
Article: 190
Helminth coinfections mitigate clinical, parasitological, and immune outcomes in Mozambican children with malaria
在莫桑比克患疟疾的儿童中，蠕虫共感染可减轻临床、寄生虫学和免疫学转归
Inocência CuambaRebeca SantanoCarlota Dobaño
Research 31 March 2026
Article: 189
Effectiveness of group-based art interventions for late-life depression: a systematic review and meta-analysis of randomized controlled trials
团体艺术干预对老年抑郁症的疗效：一项针对随机对照试验的系统综述和荟萃分析
Mohamad AzhdarlooRaziyeh AtaeiAbouzar Nazari
Research 24 February 2026
Article: 188
The associations of consultant sex on herding‑like prescribing behaviour: evidence from a web-based experiment with female primary care physicians in England
顾问性别对从众式处方行为的影响：来自一项针对英格兰女性初级保健医生的网络实验的证据
Sandro Tiziano StoffelMatthias SchwenkglenksBerna Cennet Özdemir
Research 24 February 2026
Article: 187
Tricarboxylic acid cycle metabolite index predicts adverse outcomes in acute myocardial infarction patients
三羧酸循环代谢物指数预测急性心肌梗死患者的不良预后
Ye WangPengyan WuBo Yu
Research 24 February 2026
Article: 186
Targeting cancer stem cells predicts response and reverses chemoresistance in ascites-derived ovarian cancer organoids
靶向癌症干细胞可预测腹水来源的卵巢癌类器官的反应并逆转化疗耐药性
Xiaoli ZhangWen ZhangHuiqin Guo
Research 24 February 2026
Article: 185
Neural vulnerability to stress in adolescents: a longitudinal study using polyconnectomic scoring of depression risk
青少年神经对压力的易感性：一项使用抑郁风险多连接组评分进行的纵向研究
Yuan LiuMeijuan LiJie Li
Research 24 February 2026
Article: 184
Part of 1 collection:Child and adolescent psychiatry
所属专题合集：儿童与青少年精神病学
Classification of ALS molecular subtypes: a literature review on machine learning applications and their clinical value
肌萎缩侧索硬化症分子亚型分类：机器学习应用及其临床价值的文献综述
John K. JammalEsteban A. GomezAlfredo Iacoangeli
Review 23 February 2026
Article: 183
Part of 1 collection:Amyotrophic lateral sclerosis: latest advances and novel updates
所属专题合集：肌萎缩侧索硬化症：最新进展与新动态
Can we protect refugee children from mental health problems?— a scoping review of modifiable factors to inform preventive interventions
我们能否保护难民儿童免受心理健康问题困扰？——一项旨在为预防性干预提供信息的可改变因素的范围性综述
Rita GonçalvesM J MarquesSónia Dias
Research 23 February 2026
Article: 182
Part of 1 collection:Child and adolescent psychiatry
所属专题合集：儿童与青少年精神病学
The Trial Bank initiative to promote trustworthy living evidence for medication safety (PROMISE) of children: design and pilot validation
促进儿童用药安全可信实时证据（PROMISE）的试验库计划：设计与初步验证
Chang XuSuhail A. DoiPROMISE Collaborative Research Network
Research 21 February 2026
Article: 181
Is liquid biopsy a cost-effective method to diagnose Burkitt Lymphoma in children and young adults? A health economic evaluation in Tanzania
液体活检是否为诊断坦桑尼亚儿童和青年成人伯基特淋巴瘤的一种具有成本效益的方法？一项卫生经济学评估
Jingjing JiangLiz MorrellAI-REAL Consortium
Research 21 February 2026
Article: 180
The influence of immunohistochemistry-based subtypes on overall survival in breast cancer spine metastases: a systematic review and meta-analysis
基于免疫组织化学的亚型对乳腺癌脊柱转移总生存期的影响：一项系统综述和荟萃分析
Fon-Yih TsuangYun-Heng LiChung Liang Chai
Research 21 February 2026
Article: 179
Prenatal exposure to maternal asthma and asthma medication and neurodevelopmental outcomes: a population cohort study of 179,024 children
产前接触母体哮喘及哮喘药物与神经发育结局的关系：一项针对179,024例儿童的人群队列研究
Lama A. ShakhshirSarjit SinghMichael Fleming
Research 20 February 2026
Article: 178
First-in-human phase 1/2a study of T3011, an oncolytic HSV expressing IL-12 and PD-1 antibody, administered via intratumoral (IT) injection as monotherapy in advanced solid tumors, including recurrent or metastatic HNSCC
T3011（一种表达IL-12和PD-1抗体的溶瘤性单纯疱疹病毒）首次人体1/2a期研究：通过瘤内（IT）注射作为单一疗法治疗包括复发或转移性头颈部鳞状细胞癌在内的晚期实体瘤
Dongmei JiWenmin FuXichun Hu
Research 20 February 2026
Article: 177
Expanding access to cerebrovascular imaging with routine MRI for pre-surgical assessment of intracranial tumor patients: an AI model development and multi-center validation study
利用常规MRI扩大脑血管成像在颅内肿瘤患者术前评估中的应用范围：一项人工智能模型开发与多中心验证研究
Chaoyue ChenZhouyang HuangJianguo Xu
Research 20 February 2026
Article: 176
Changing landscape of physical fitness and urban–rural inequalities: evidence from 1.2 million children and adolescents over 20 years of urbanization
20年城市化进程中120万例儿童和青少年体质健康状况及城乡差异的变化
Shan CaiJiaxin LiYi Song
Research 19 February 2026
Article: 175
Efficacy and safety of anti-prediabetic drugs in patients with prediabetes: a Bayesian network meta-analysis
抗糖尿病前期药物在糖尿病前期患者中的疗效和安全性：一项贝叶斯网状荟萃分析
Yike WuZihan WangGuo Ma
Research 19 February 2026
Article: 174
Clonal haematopoiesis of indeterminate potential and risk of incident psychiatric disorders
Yuefeng YuChenyi WanNingjian Wang
意义未明的克隆性造血与新发精神障碍风险
Research 18 February 2026
Article: 173
Spatial characterization of intrahepatic fat deposition across steatotic liver disease subcategories: a multicenter study
脂肪性肝病各亚类中肝内脂肪沉积的空间特征：一项多中心研究
Yan-Ci ZhaoMin WangFeng Chen
Research 18 February 2026
Article: 172
Pregnancy outcomes among medically complex populations with high risk of pregnancy mortality in Virginia: a retrospective observational study
弗吉尼亚州妊娠死亡高风险医学复杂人群的妊娠结局：一项回顾性观察研究
Michael J. GreenLauren G. AndersonJonas J. Swartz
Research 18 February 2026
Article: 171
Maternal amino acid metabolites during pregnancy and preterm birth: results from two prospective cohort studies
孕期母体氨基酸代谢物与早产的关系：两项前瞻性队列研究的结果
Jingnan ChenYidan DongJu-Sheng Zheng
Research 18 February 2026
Article: 170
Correction: Trajectory of the body weight after drug discontinuation in the treatment of anti-obesity medications
更正：停用抗肥胖药物后体重的变化轨迹
Han WuWenjia YangLinong Ji
Correction 25 March 2026
Article: 169
Physical activity patterns and cardiovascular disease risk in adults with overweight or obesity: a prospective cohort study
超重或肥胖成人身体活动模式与心血管疾病风险：一项前瞻性队列研究
Kai MuYanan QiaoBo Xi
Research 16 February 2026
Article: 168
Part of 1 collection:Weight loss interventions and their health impacts
所属专题合集：减肥干预措施及其对健康的影响
Maternal migraine and offspring ADHD: triangulating the evidence
母亲偏头痛与后代多动症（ADHD）：多方证据综合分析
Yaxin LuoChristina DardaniEvie Stergiakouli
Research 14 February 2026
Article: 167
Part of 1 collection:Child and adolescent psychiatry
所属专题合集：儿童与青少年精神病学
An autonomous siRNA delivery system targeting NLRP3: implications in Parkinson’s disease
靶向NLRP3的自主性小干扰RNA（siRNA）递送系统：在帕金森病中的潜在意义
Lishan LinZhizong LiZhong Pei
Research 12 February 2026
Article: 166
Lay descriptions of painful temporomandibular disorders—an international consensus proposal for Global Burden of Disease estimates
颞下颌关节紊乱病疼痛的通俗描述——全球疾病负担评估的国际共识提案
A. LövgrenP. LivP. Svensson
Research 17 March 2026
Article: 165
Association of soluble tumor necrosis factor receptor 1 with tau pathology, brain atrophy, and cognitive decline: a longitudinal study
可溶性肿瘤坏死因子受体1与tau蛋白病变、脑萎缩及认知功能下降的关联：一项纵向研究
Yutong ZhangLulu SunAlzheimer’s Disease Neuroimaging Initiative
Research 11 February 2026
Article: 164
Part of 1 collection:Healthy aging and longevity: the role of preventive medicine and risk factors
所属专题合集：健康老龄化与长寿：预防医学和风险因素的作用
Particulate matter and respiratory health in middle-aged and older adults: disentangling size-fractionated and constituent-specific effects under China’s clean-air policies
颗粒物与中老年人呼吸系统健康的关系：厘清中国净化空气政策下不同粒径及成分的特定影响
Yujing ChenZhaoyan LiuYu-ming Chen
Research 11 February 2026
Article: 163
Part of 1 collection:Climate change and human health
所属专题合集：气候变化与人类健康
Clinical impact and cost-effectiveness of vaccinating infants and adolescents against invasive meningococcal B disease in the Netherlands
荷兰为婴儿和青少年接种针对侵袭性脑膜炎球菌B病的疫苗的临床影响和成本效益
Thomas OttenMirjam KnolAnneke Steens
Research 10 February 2026
Article: 162
Association between trajectories of sleep quality and postpartum depression: a group-based trajectory model and computer-simulated network analysis
睡眠质量轨迹与产后抑郁之间的关联：基于组别的轨迹模型和计算机模拟网络分析
Xiaoxiao MeiJinzhou YuZengjie Ye
Research 10 February 2026
Article: 161
Part of 1 collection:Sleep and mental health
所属专题合集：睡眠与心理健康
Understanding Japan’s mortality advantage: a comparison of mortality in independent and dependent older adults in Japan and Sweden
解读日本在死亡率方面的优势：日本与瑞典独立生活及依赖他人生活老年人的死亡率比较
Shunsuke MurataMarcus EbelingKarin Modig
Research 23 March 2026
Article: 160
Part of 1 collection:Healthy aging and longevity: the role of preventive medicine and risk factors
所属专题合集：健康老龄化与长寿：预防医学及风险因素的作用
The Young Adult Sleep model: an evolving causal loop diagram of mental health dynamics
青年睡眠模型：心理健康动态演变的因果环路图
Jeroen F. UlemanRushd F. M. Al-ShamaNaja Hulvej Rod
Research 16 March 2026
Article: 159
Part of 1 collection:Sleep and mental health
所属专题合集：睡眠与心理健康
Oncostatin-M ligand-based CAR-T therapy displays robust anti-tumor activity against osteosarcoma
基于抑瘤素M配体的CAR-T疗法对骨肉瘤显示出强大的抗肿瘤活性
Daniel FeinbergVinayak UppinReshmi Parameswaran
Research 17 March 2026
Article: 158
Antimicrobial catheters coated with poly-L-lysine for the prevention of bacteriuria in adults requiring short-term catheterization: a multicenter randomized controlled trial
涂有聚-L-赖氨酸的抗菌导管预防短期导尿成人患者菌尿症：一项多中心随机对照试验
Xinfei LiJun LiuKai Zhang
Research 09 February 2026
Article: 157
Penpulimab in combination with lenalidomide and R-GemOx regimen (R2-GemOx-PD1i) in relapsed or refractory diffuse large B-cell lymphoma: a multicenter, single-arm, phase 2 trial
派安普利单抗联合来那度胺和R-GemOx方案（R2-GemOx-PD1i）治疗复发或难治性弥漫性大B细胞淋巴瘤：一项多中心、单臂、2期试验
Jin-Hua LiangTong-Yao XingWei Xu
Research 09 February 2026
Article: 156
Digital twin brain reveals state-specific stimulation targets for abnormal brain dynamics in tinnitus
数字孪生大脑揭示耳鸣异常脑动力学状态特异性刺激靶点
Jiaqi ZhangShuting HanTianzi Jiang
Research 10 February 2026
Article: 155
The case for mandatory reporting to enable targets for healthy and environmentally sustainable food: means, motive and opportunity
强制报告实现健康且环境可持续食物目标的理由：方法、动机和机会
Rachel PecheyLauren BandySusan A. Jebb
Debate 10 February 2026
Article: 154
Genetic insights into radiomic and proteomic changes under β1-blockers treatment in hypertensive heart disease and hypertrophic cardiomyopathy
β1受体阻滞剂治疗高血压性心脏病和肥厚型心肌病时放射组学和蛋白质组学变化的遗传学见解
Zhe ChenYifan TangKai Xie
Research 09 February 2026
Article: 153
Part of 1 collection:Cardiomyopathy and cardiac arrhythmias
所属专题合集：心肌病与心律失常
Optimizing drug-resistant tuberculosis diagnosis: cost-effectiveness of rapid molecular and phenotypic assays in South Africa
优化耐药结核病诊断：南非快速分子和表型检测方法的成本效益分析
Ginenus FekaduTadesse TolossaWai Kit Ming
Research 09 February 2026
Article: 152
Maternal smoking based on pre-birth health examination and risk of neurodevelopmental disorders in offspring: insights from a Korean mother–child cohort
基于产前健康检查探讨母亲吸烟与后代神经发育障碍风险的关系：来自韩国母婴队列研究的见解
Chan Soon ParkMoonyoung JangJun-Bean Park
Research 11 March 2026
Article: 151
Part of 1 collection:Child and adolescent psychiatry
所属专题合集：儿童与青少年精神病学
Effects of ablation versus drug therapy on clinical outcomes and quality of life by frailty status in atrial fibrillation: a post hoc analysis of the CABANA trial
根据衰弱状态分析消融术与药物治疗对心房颤动患者临床预后和生活质量的影响：CABANA试验的事后分析
Lili WangYanguang LiYunlong Wang
Research 07 February 2026
Article: 150
Part of 1 collection:Cardiomyopathy and cardiac arrhythmias
所属专题合集：心肌病与心律失常
Quantifying lifetime risk for 1,401 infectious diseases across the diabetes spectrum using a Bayesian approach
采用贝叶斯方法量化糖尿病全病程中1401种传染病的终生风险
Boomer B. OlsenMartin Tristani-FirouziEdgar Javier Hernandez
Research 07 February 2026
Article: 149
Part of 1 collection:Diabetes and infectious disease
所属专题合集：糖尿病与传染病
Risk assessment of asthma and allergic rhinitis in atopic dermatitis patients treated with biologics and JAK inhibitors: a systematic review and network meta-analysis of randomized controlled trials
对接受生物制剂和JAK抑制剂治疗的特应性皮炎患者罹患哮喘和过敏性鼻炎的风险评估：一项针对随机对照试验的系统综述和网络荟萃分析
Liling ZengTong ZhouJing Li
Research 07 February 2026
Article: 148
Preclinical activity of brincidofovir in peripheral T-cell and NK/T-cell lymphoma
布林西多福韦（brincidofovir）在外周T细胞和NK/T细胞淋巴瘤中的临床前活性
Jason Yongsheng ChanElizabeth Chun Yong LeeChoon Kiat Ong
Research 06 February 2026
Article: 147
Genetic risk factors modulate the association between physical activity and colorectal cancer
遗传风险因素调节身体活动与结直肠癌之间的关联
Anita R. PeoplesMireia Obón-SantacanaVictor Moreno
Research 05 February 2026
Article: 146
A neuroimaging biomarker for disease staging in clinically diagnosed Alzheimer’s disease
临床诊断阿尔茨海默病的疾病分期神经影像学标志物
Zhuangzhuang LiShaozhen YanYong Liu
Research 05 February 2026
Article: 145
Association of GLP-1 receptor agonists with herpes risks in diabetes mellitus: a target trial emulation
胰高血糖素样肽-1（GLP-1）受体激动剂与糖尿病中疱疹风险的关联：一项目标试验模拟研究
Chi-Hsien HuangI-Hui ChiangJames Cheng-Chung Wei
Research 31 December 2025
Article: 144
Part of 1 collection:Diabetes and infectious disease
所属专题合集：糖尿病与感染性疾病
Neoadjuvant immunochemotherapy plus thymalfasin in locally advanced gastric cancer: a prospective clinical trial
局部晚期胃癌联合胸腺肽的新辅助免疫化疗：一项前瞻性临床试验
Hao XuFengyuan LiZekuan Xu
Research 26 February 2026
Article: 143
Part of 1 collection:Clinical trials for gastrointestinal cancer
所属专题合集：胃肠道癌症的临床试验
Detection of sequelae from acute meningitis during clinical review by a healthcare provider: a systematic review and meta-analysis
临床医生在临床复查中检测急性脑膜炎后遗症：一项系统综述和荟萃分析
Luisa F. AlvizCarla Y. KimKiran T. Thakur
Research 28 February 2026
Article: 142
Part of 1 collection:Acute meningitis: a collection of systematic reviews
所属专题合集：急性脑膜炎：系统综述合集
ISG15-driven immune modulation and tumor progression in breast cancer metastasis: insights from single-cell and spatial transcriptomics
ISG15驱动的免疫调节与乳腺癌转移中的肿瘤进展：来自单细胞和空间转录组学的见解
Hua ShaoHanlu TangYongqing Xu
Research 04 February 2026
Article: 141
Evaluating the impact of family history and polygenic risk scores on cardiometabolic disease risk
评估家族史和多基因风险评分对心代谢疾病风险的影响
Ebuka OnyenobiKnightess OyiboSally N. Adebamowo
Research 03 February 2026
Article: 140
Social networking site use, depressive and anxiety symptoms in adolescents: evidence from a longitudinal cohort study (SCAMP)
社交网站使用与青少年抑郁和焦虑症状：来自纵向队列研究（SCAMP）的证据
Chen ShenBraulio M. Girela-SerranoMireille B. Toledano
Research 03 February 2026
Article: 139
Part of 1 collection:Child and adolescent psychiatry
所属专题合集：儿童与青少年精神病学
Early gestational prediction of spontaneous preterm birth using a validated three-protein serum biomarker panel
使用经验证的三蛋白血清生物标志物组合进行早孕期自发性早产预测
Qiong LuoJuan WeiXuefeng B. Ling
Research 02 February 2026
Article: 138
Household cannabis cessation and adolescent mental health outcomes in a prospective cohort study
一项前瞻性队列研究中家庭大麻戒断与青少年心理健康预后的关系
Ming WangYixiang XuFei Li
Research 02 February 2026
Article: 137
Part of 1 collection: Psychoactives: Recreational drugs repurposed as novel therapies
所属专题合集：精神活性物质：娱乐性药物重新利用为新型疗法
Objective assessment of long-term impact of COVID-19 on multiple sensory functions
客观评估新冠肺炎对多种感觉功能的长期影响
Ahmad OdehVeronica L. FormanekKai Zhao
Research 27 February 2026
Article: 136
Detection of hearing loss by formal audiological testing after acute infectious meningitis: a global systematic review and meta-analysis
急性感染性脑膜炎后通过正式听力检测诊断听力损失：一项全球系统综述和荟萃分析
Luisa F. AlvizCarla Y. KimKiran T. Thakur
Review 28 February 2026
Article: 135
Part of 1 collection: Acute meningitis: a collection of systematic reviews
所属专题合集：急性脑膜炎：系统综述合集
Serological evidence of substantial respiratory syncytial virus infection burden among older adults residing in Swedish long-term care facilities
血清学证据表明，居住在瑞典长期护理机构中的老年人存在沉重的呼吸道合胞病毒感染负担
Preeti MoarChristoffer GranvikMattias N. E. Forsell
Research 24 February 2026
Article: 134
Association of parental education with offspring psychiatric diagnoses, violent crimes, and suicidal behavior: a nationwide Swedish quasi-experimental study
父母受教育程度与后代精神疾病诊断、暴力犯罪和自杀行为之间的关联：一项瑞典全国范围的准实验研究
Mengping ZhouHenrik LarssonErik Pettersson
Research 26 February 2026
Article: 133
Discriminative performance of externally validated dementia risk prediction models: a systematic review and meta-analysis
外部验证的痴呆风险预测模型的鉴别性能：一项系统综述和荟萃分析
Blossom C. M. StephanJacob BrainMario Siervo
Research 02 February 2026
Article: 132
Part of 1 collection:Healthy aging and longevity: the role of preventive medicine and risk factors
所属专题合集：健康老龄化与长寿：预防医学和风险因素的作用
Efficacy and safety of intravenous administration of high-dose selenium for preventing chemotherapy-induced peripheral neuropathy in platinum-sensitive recurrent ovarian cancer: a phase 3, double-blind, parallel group, randomized controlled pilot study
静脉注射大剂量硒预防铂敏感复发性卵巢癌化疗所致周围神经病变的有效性和安全性：一项3期、双盲、平行组、随机对照试点研究
Ga Won YimKyung Hee HanHee Seung Kim
Research 02 February 2026
Article: 131
Time for change in implementation research and practice
实施研究和实践中变革的时机已到
Mike EnglishJacob McKnightSebastian Fuller
Debate 02 February 2026
Article: 130
CardioMetAge estimates cardiometabolic aging and predicts disease outcomes
CardioMetAge可评估心脏代谢年龄并预测疾病结局
Yucan LiXinming XuKelin Xu
Research 31 January 2026
Article: 129
Disproportionate climate burden of rising temperatures on low birth weight in Pakistan
气温上升给巴基斯坦低出生体重儿带来的不成比例的气候负担
Syeda H. FatimaCorey J. A. BradshawZohra S. Lassi
Research 31 January 2026
Article: 128
Part of 1 collection: Climate change and human health
所属专题：气候变化与人类健康
Enhancing oncolytic virotherapy with a tri-specific T-cell engager targeting CD3ε, EpCaM, and 4-1BB: preclinical evaluation and implications for cancer immunotherapy
利用靶向CD3ε、EpCaM和4-1BB的三特异性T细胞衔接器增强溶瘤病毒疗法：临床前评估及对癌症免疫疗法的启示
Zhongyi DongHaoyu ZhangZizhen Zhang
Research 30 January 2026
Article: 127
Targeting BCL-XL for degradation synergizes with gemcitabine against cholangiocarcinoma
靶向降解BCL-XL与吉西他滨联用对胆管癌具有协同治疗作用
Qinghua ZengYan ZhangYonghan He
Research 30 January 2026
Article: 126
Association of DNA methylation with hypertension and blood pressure: a 7-year longitudinal study from KORA F4/FF4
DNA甲基化与高血压及血压的关联：来自KORA F4/FF4的7年纵向研究
Liye LaiAngelina Shin Yee JongMelanie Waldenberger
Research 04 February 2026
Article: 125
Shared genetic architecture of psychoactive substance use and pan-cancer: insights from a large‑scale genome‑wide cross‑trait analysis
精神活性物质使用与泛癌症的共享遗传结构：来自大规模全基因组跨性状分析的见解
Jiahang SongPengzhu LiOlivier Gires
Research 05 February 2026
Article: 124
Part of 1 collection: Psychoactives: Recreational drugs repurposed as novel therapies
所属专题：精神活性物质：作为新型疗法的娱乐性药物再利用
Intrauterine exposure to maternal diabetes and the risk of developing epilepsy in children: a national cohort study of 2.3 million children
宫内暴露于母体糖尿病与儿童患癫痫风险的关系：一项针对230万儿童的全国队列研究
Muhammad Zakir HossinMartina PerssonNeda Razaz
Research 14 February 2026
Article: 123
ADHD and adherence to antihypertensive medication treatment: a multinational cohort study
多动症与坚持抗高血压药物治疗的关系：一项多国队列研究
Honghui YaoYiling ZhouZheng Chang
Research 20 February 2026
Article: 122
How effective is rejoining a long-term weight loss program? The 5- and 10-year MRI-assessed Follow Interventions Trial (FIT) project
重新加入长期减肥计划的效果如何？5年和10年磁共振成像评估的随访干预试验（FIT）项目
Hadar KleinDafna PachterIris Shai
Research 30 January 2026
Article: 121
Part of 1 collection: Weight loss interventions and their health impacts
所属专题：减肥干预措施及其对健康的影响
Correction: Brain state dynamics and working memory in patients with schizophrenia and unaffected siblings
更正：精神分裂症患者及其未受影响兄弟姐妹的脑状态动态与工作记忆
Feiwen WangJie YangLena Palaniyappan
Correction 20 February 2026
Article: 120
Ocular light and optical radiation exposure as a modifiable environmental determinant of health: expert consensus on research gaps and priorities
作为可改变的环境健康决定因素的眼睛光暴露和光学辐射暴露：关于研究空白和优先事项的专家共识
Manuel SpitschanAnna M. BillerJohannes Zauner
Guideline 29 January 2026
Article: 119
Dietary patterns and neuropsychological function in adolescents: a cross-sectional and longitudinal study
青少年饮食模式与神经心理功能：一项横断面和纵向研究
Alexios ManidisNicolas Ayala-AldanaJordi Julvez
Research 29 January 2026
Article: 118
Part of 1 collection: Child and adolescent psychiatry
所属专题：儿童与青少年精神病学
Factors impacting the delivery of contextualized care in serious illness: a focus group study with healthcare professionals
影响危重症患者情境化护理实施的因素：一项针对医疗保健专业人员的焦点小组研究
Linda ModderkolkYvonne SchoonAnne B. Wichmann
Research 29 January 2026
Article: 117
Part of 1 collection: Palliative care and medicine
所属专题：姑息治疗与医学
Early interventions for first onset of symptoms of mental health conditions: an umbrella review of systematic reviews
针对心理健康问题首次出现症状的早期干预措施：一项系统综述的伞式评价
Jasmine LeePhoebe BarnettSonia Johnson
Research 29 January 2026
Article: 116
Harmonic patterns embedded in ictal EEG signals in focal epilepsy: new insight into the epileptogenic zone
局灶性癫痫发作间期脑电图信号中嵌入的谐波模式：对致痫区的新见解
Lingli HuLingqi YeShuang Wang
Research 28 January 2026
Article: 115
Part of 1 collection: Epilepsy: Seizure prevention, treatment, and epidemiology
所属专题合集：癫痫：发作预防、治疗和流行病学
Effects of aerobic or resistance exercise on sleep and cancer-related fatigue in patients with breast cancer during or after neoadjuvant chemotherapy: a 3-arm randomized controlled trial
有氧运动或抗阻运动对新辅助化疗期间或之后乳腺癌患者睡眠和癌症相关疲劳的影响：一项三臂随机对照试验
Alexander HaussmannMartina E. SchmidtKaren Steindorf
Research 28 January 2026
Article: 114
Neutrophil methylmalonic acid promotes microthrombus formation and adverse cardiac remodeling post-myocardial infarction through activating IL-6 signaling pathway-mediated NETosis
中性粒细胞甲基丙二酸通过激活IL-6信号通路介导的中性粒细胞胞外诱捕网形成（NETosis），促进心肌梗死后微血栓形成和不良心脏重构
Yige LiuJiaxin WangShaohong Fang
Research 28 January 2026
Article: 113
Statistical approaches to analyse the combined effect of seven air pollutants and breast cancer risk: a case–control study nested in the French E3N-Generations cohort
分析七种空气污染物联合作用与乳腺癌风险关系的统计方法：一项嵌套于法国E3N-Generations队列的病例对照研究
Camille GiampiccoloBéatrice FerversAmina Amadou
Research 28 January 2026
Article: 112
Part of 1 collection: Carcinogens and human health
所属专题合集：致癌物与人类健康
Is behaviour change communication guidance for general practice healthcare professionals evidence based? A systematic review
针对全科医疗保健专业人员的行为改变沟通指导是否具有循证依据？一项系统综述
Anika Schwarze-ChintapatlaJonathan Livingstone-BanksCharlotte Albury
Research 16 February 2026
Article: 111
Patient-centred postpartum care provision: virtual delivery, tiered escalation, and tensions between efficiency, preference, and clinical concern
以患者为中心的产后护理服务提供：虚拟服务模式、分级转诊机制，以及效率、患者偏好与临床关切之间的矛盾
Sergio A. SilverioJulia R. B. BrownEmma L. Duncan
Research 24 February 2026
Article: 110
Ethical dilemmas in climate change and healthcare delivery: a cross-sectional survey of US patient perspectives
气候变化与医疗服务中的伦理困境：一项针对美国患者观点的横断面调查
Andrew HantelEmily SenayGregory A. Abel
Research 27 January 2026
Article: 109
Part of 1 collection: Climate change and human health
所属专题：气候变化与人类健康
Inetetamab plus camrelizumab and utidelone for pretreated HER2-positive advanced breast cancer: a prospective, single-arm, phase 2 study
伊尼妥单抗联合卡瑞利珠单抗和优替德隆治疗既往接受过治疗的HER2阳性晚期乳腺癌：一项前瞻性、单臂、2期研究
Huimin LvTao SunMin Yan
Research 27 January 2026
Article: 108
Potential of earlier primary care health checks for prevention of cardiovascular events in younger age groups: population-based study in the United Kingdom
早期初级保健健康检查对预防年轻人群心血管事件的潜力：英国一项基于人群的研究
Catherine A. ScottLinxin LiPeter M. Rothwell
Research 24 January 2026
Article: 107
Comparative effects of salt substitutes on blood pressure, cardiovascular events and mortality: a systematic review and network meta-analysis
盐替代品对血压、心血管事件和死亡率影响的比较：一项系统综述和网络荟萃分析
Honghao LaiGihad NesrallahBradley C. Johnston
Research 23 January 2026
Article: 106
Association of short-term exposure to ambient air pollutants with liver function and mediation by fasting insulin: evidence from a rural cohort in China
短期暴露于环境空气污染物与肝功能的关系及空腹胰岛素的中介作用：来自中国农村队列研究的证据
Mengxin WangAogang ZhangWeidong Wu
Research 23 January 2026
Article: 105
Part of 1 collection:Climate change and human health
所属专题：气候变化与人类健康
Adjuvant tislelizumab, lenvatinib, and capecitabine for resected biliary tract cancer: a prospective phase II trial
辅助治疗：替雷利珠单抗、仑伐替尼和卡培他滨用于可切除的胆道癌：一项前瞻性II期试验
Yun FengNing ZhangLu Wang
Research 23 January 2026
Article: 104
Comparative effectiveness of sleeve gastrectomy and semaglutide for weight loss and metabolic outcomes: a prospective non-randomized study
袖状胃切除术与司美格鲁肽对减重及代谢结局的疗效比较：一项前瞻性非随机研究
Yutung YenQian ZhangYi Chen
Research 22 January 2026
Article: 103
Part of 1 collection:Weight loss interventions and their health impacts
所属专题：减重干预措施及其对健康的影响
Impact of sex on outcomes in patients treated with drug-coated balloons versus drug-eluting stents for de novo coronary artery lesions: Insights from the REC-CAGEFREE I trial
性别对接受药物涂层球囊与药物洗脱支架治疗的新发冠状动脉病变患者预后的影响：来自REC-CAGEFREE I试验的见解
Ping WangJingyu ZhouLing Tao
Research 22 January 2026
Article: 102
Assessing the comorbidity between asthma and depression through polygenic risk scoring and time-to-event models
通过多基因风险评分和时间事件模型评估哮喘与抑郁的共病情况
Xueting WangJun HeRenato Polimanti
Research 22 January 2026
Article: 101
Persistent immune, coagulation and cardiac dysregulation are correlated with later post-discharge mortality in children with severe malnutrition
严重营养不良儿童出院后持续存在的免疫、凝血和心脏功能失调与后期死亡率相关
Brenda KamauEvans O. MudiboJames M. Njunge
Research 22 January 2026
Article: 100
Correction: Computer assisted verbal autopsy: comparing large language models to physicians for assigning causes to 6939 deaths in Sierra Leone from 2019–2022
更正：计算机辅助口头尸检：对比大型语言模型与医生为2019 - 2022年塞拉利昂6939例死亡分配病因的情况
Richard WenAnteneh Tesfaye AssalifRashid Ansumana
Correction 14 February 2026
Article: 99
Characteristics of parks associated with depression in women only: a cross-sectional study of 329,363 adults
仅与女性抑郁相关的公园特征：一项针对329,363名成年人的横断面研究
Jonathan R. OlsenNatalie NichollsRichard Mitchell
Research 21 January 2026
Article: 98
Weight change mediates the effect of lifestyle intervention on postpartum diabetes in women with prior gestational diabetes: a secondary analysis of a randomized clinical trial
在生活方式干预对既往妊娠期糖尿病女性产后糖尿病影响中，体重变化的中介作用：一项随机临床试验的二次分析
Weiqin LiHuikun LiuGang Hu
Research 21 January 2026
Article: 97
Part of 1 collection: Diagnosis and management of gestational diabetes
所属专题：妊娠期糖尿病的诊断与治疗
Global drivers of heart failure attributable to atrial fibrillation/flutter: insights fromJoinpoint regression, age-period-cohort analysis, and future projections from the GBD 2021 Study
心房颤动/扑动所致心力衰竭的全球驱动因素：来自折点回归、年龄-时期-队列分析以及2021年GBD（全球疾病负担）研究未来预测的见解
Jing ChenZhu LiGregory Y. H. Lip
Research 20 January 2026
Article: 96
Part of 1 collection: Cardiomyopathy and cardiac arrhythmias
所属专题：心肌病与心律失常
Overdiagnosis of gestational diabetes mellitus during Ramadan: a retrospective population-based study in Catalonia, Spain
斋月期间妊娠期糖尿病的过度诊断：西班牙加泰罗尼亚地区一项基于人群的回顾性研究
Marta CarrascoBogdan VlachoMarta Hernández
Research 20 January 2026
Article: 95
Part of 1 collection: Diagnosis and management of gestational diabetes
所属专题：妊娠期糖尿病的诊断与管理
Why current risk factor-based approaches fall short in predicting stillbirth: a national cohort study of nulliparous women in England
为何当前基于风险因素的方法在预测死胎方面存在不足：英格兰初产妇全国队列研究
A. HowellB. ThilaganathanTommy’s National Centre for Maternity Improvement
Research 22 January 2026
Article: 94
Pay-it-forward intervention increased pneumococcal vaccine uptake among older adults in China: a randomized controlled trial
爱心传递干预措施提高了中国老年人肺炎球菌疫苗的接种率：一项随机对照试验
Jiao QinChunxing TaoBingyu Liang
Research 19 January 2026
Article: 93
The impact of e-cigarette taxation: a systematic review and meta-analysis on usage, pricing strategies, and public health implications
电子烟税收的影响：针对使用情况、定价策略和公共卫生影响开展的系统综述和荟萃分析
Quan WangZheng ZhuLi Yang
Research 17 January 2026
Article: 92
Safety and preliminary efficacy results of IBI389, an anti-Claudin18.2×CD3 bispecific antibody, in patients with solid tumors and gastric or gastro-esophageal tumors: a phase 1 dose escalation and expansion study
抗Claudin18.2×CD3双特异性抗体IBI389在实体瘤及胃或胃食管肿瘤患者中的安全性与初步疗效结果：一项1期剂量递增与扩展研究
Xiaoyu LiRuihong DaiFeng Bi
Research 16 January 2026
Article: 91
Part of 1 collection: Clinical trials for gastrointestinal cancer
所属专题：胃肠道癌症临床试验
Comparative risk of delirium among opioid users for non-cancer pain: a retrospective cohort study
比较非癌症疼痛使用阿片类药物者发生谵妄的风险：一项回顾性队列研究
Carlos Raul Ramirez MedinaMark LuntMeghna Jani
Research 31 January 2026
Article: 90
Association between preoperative interruption of antiplatelet therapy and postoperative thrombotic risk after minimally invasive surgery for abdominopelvic cancer in patients treated with P2Y12 inhibitors
接受P2Y12抑制剂治疗的患者行腹部盆腔癌症微创手术时，术前中断抗血小板治疗与术后血栓形成风险之间的关联
Masashi KubotaSatomi YoshidaKoji Kawakami
Research 16 January 2026
Article: 89
Comparative outcomes of distal ureterectomy vs. radical nephroureterectomy in high-risk distal ureteral urothelial carcinoma: a two-center cohort study in Northern and Southern China
高危远端输尿管尿路上皮癌患者行远端输尿管切除术与根治性肾输尿管切除术的疗效比较：中国北方和南方两家中心的队列研究
Junyi XieZhenhua LiuWei Yu
Research 16 January 2026
Article: 88
Co-occurrence patterns and related risk factors of dementia and Parkinson’s disease among older adults across 204 countries and territories: a spatial correspondence and systematic analysis
204个国家和地区老年人痴呆症与帕金森病共现模式及相关危险因素：空间对应与系统分析
Weiyang ChenMin DuJue Liu
Research 15 January 2026
Article: 87
Accelerated brain aging in amyotrophic lateral sclerosis and its prognostic associations: a cohort study
肌萎缩侧索硬化症加速脑衰老及其预后关联：一项队列研究
Chenhao FangJiaoting JinShuoqiu Gan
Research 15 January 2026
Article: 86
Part of 1 collection: Amyotrophic lateral sclerosis: latest advances and novel updates
所属专题：肌萎缩侧索硬化症：最新进展与新动态
The clinical effects and cortical mechanism of rTMS in poststroke lateropulsion: a randomized controlled trial
重复经颅磁刺激（rTMS）对脑卒中后侧方倾倒的临床效果及皮质机制：一项随机对照试验
Lijiao MengRaymond C. C. TsangQuan Wei
Research 14 January 2026
Article: 85
5-HT2C receptors in the glutamatergic neurons of dorsal raphe nucleus orchestrate the comorbidity of pain and anxiety in mice
中脑背侧缝际核谷氨酸能神经元中的5-HT2C受体调控小鼠疼痛与焦虑共病
Qi ZhangLi XieRiyue Jiang
Research 13 January 2026
Article: 84
The clinical landscape of POLE-mutant colorectal cancer: a retrospective analysis of real-world outcome
POLE突变型结直肠癌的临床现状：一项现实结局的回顾性分析
Ting XuXuhui ZhangJian Li
Research 13 January 2026
Article: 83
The efficacy and safety of duloxetine in treating refractory chronic cough: a randomized clinical trial
度洛西汀治疗难治性慢性咳嗽的有效性和安全性：一项随机临床试验
Shengyuan WangHeng WuXianghuai Xu
Research 13 January 2026
Article: 82
Impact of diagnosis to ablation time on clinical outcomes in patients with atrial fibrillation: post hoc analysis of the CABANA trial
心房颤动患者从诊断到消融的时间对临床预后的影响：CABANA试验的事后分析
Manlin ZhaoYang ChenGregory Y. H. Lip
Research 12 January 2026
Article: 81
Part of 1 collection: Cardiomyopathy and cardiac arrhythmias
所属专题：心肌病与心律失常
Elevated maternal pre-transfer serum lipid peroxidation is associated with implantation failure and early pregnancy loss
母体转运前血清脂质过氧化水平升高与着床失败和早期流产相关
Zhangwei JiaJunxiang RenJunhao Yan
Research 12 January 2026
Article: 80
Impact of Helicobacter pylori infection on gut and intratumoral microbiome and its association with immunotherapy response in gastrointestinal cancer
幽门螺杆菌感染对肠道和肿瘤内微生物组的影响及其与胃肠道癌症免疫治疗反应的关联
Keren JiaYang ChenLin Shen
Research 12 January 2026
Article: 79
Part of 1 collection: Gut microbiota: New treatments of human disease
所属专题：肠道微生物组：人类疾病的新疗法
SGLT-2 Inhibitor use and liver-related and mortality outcomes in patients with type 2 diabetes and compensated cirrhosis
SGLT-2抑制剂在2型糖尿病合并代偿性肝硬化患者中的应用及其对肝脏相关预后和死亡率的影响
Tien-Shin ChouDaniel Hsiang-Te TsaiEdward Chia-Cheng Lai
Research 12 January 2026
Article: 78
Extrapolating from trials to clinic: a predictive model defining the boundaries of benefit for multiple sclerosis therapies in real-world populations based on systematic review
从试验外推至临床：基于系统综述构建预测模型，界定多发性硬化症疗法在现实人群中的获益边界
Bibiana BielekovaTianxia WuMichael Calcagni
Research 10 January 2026
Article: 77
A validated model for early prediction of group A streptococcal aetiology in necrotising soft tissue infections using minimal patient data
利用最少患者数据早期预测坏死性软组织感染A组链球菌病因的验证模型
Sonja KatzJaco SuijkerEdoardo Saccenti
Research 10 January 2026
Article: 76
Trends in lipid-lowering therapies in acute coronary syndromes after Chinese new insurance policy: a real-world analysis
中国新医保政策实施后急性冠状动脉综合征患者降脂治疗趋势：一项现实情况分析
Xin ZhaoShujing WuJunbo Ge
Research 09 January 2026
Article: 75
Fragmented healthcare and effective maternal coverage in Mexico, 2009–2023
2009-2023年墨西哥医疗体系碎片化与有效孕产妇医疗保障
Edson Serván-MoriDiego Cerecero-GarcíaOctavio Gómez-Dantés
Research 09 January 2026
Article: 74
Circadian rhythm disruption in cardiovascular disease: a systematic review and meta-analysis of mechanistic evidence from animal models
昼夜节律紊乱与心血管疾病：基于动物模型机制证据的系统综述与荟萃分析
Mrinal K. DasEvi De RyckJohanna Samulin Erdem
Research 09 January 2026
Article: 73
Frailty progression: The role of multimorbidity configurations in frailty transitions and predicting mortality risk among older adults
衰弱进展：多重共病组合模式在老年人衰弱状态转变及死亡风险预测中的作用
Rafael Ogaz-GonzálezQian ZouEva Corpeleijn
Research 08 January 2026
Article: 72
Part of 1 collection: Healthy aging and longevity: the role of preventive medicine and risk factors
所属专题：健康老龄化与长寿：预防医学及风险因素的作用
Effect of probiotic supplementation on the gut microbiota diversity in healthy populations: a systematic review and meta-analysis of randomised controlled trials
益生菌补充剂对健康人群肠道微生物群多样性的影响：一项针对随机对照试验的系统综述和荟萃分析
Anna Júlia ÉliásKincső Csepke Földvári-NagyLászló Földvári-Nagy
Research 07 January 2026
Article: 71
Part of 1 collection: Gut microbiota: New treatments of human disease
所属专题：肠道微生物群：人类疾病的新疗法
Pain and high-impact pain in community-dwelling older adults in Australia and relation to sociodemographic and health-related factors, including physical disability, psychological distress, and quality of life
澳大利亚社区居住老年人的疼痛及重度疼痛情况，及其与社会人口统计学因素和健康相关因素（包括身体残疾、心理困扰和生活质量）的关系
Grace JoshySaman Khalatbari-SoltaniEmily Banks
Research 22 January 2026
Article: 70
Mortality and morbidity burden associated with smoking: evidence from a 1.6 million cohort in Hong Kong
与吸烟相关的死亡率和发病率负担：来自香港160万人队列研究的证据
Boyuan WangTingting ChenEric Yuk Fai Wan
Research 06 January 2026
Article: 69
Part of 1 collection:Carcinogens and human health
所属专题：致癌物与人类健康
Association between long-term extreme high temperature and mortality: a 9-million prospective cohort study
长期极端高温与死亡率之间的关系：一项900万人的前瞻性队列研究
Bo YinQi HuangKuiying Gu
Research 06 January 2026
Article: 68
Part of 1 collection:Climate change and human health
所属专题：气候变化与人类健康
Unraveling the neurotoxic mechanisms of tranexamic acid in epilepsy induction: a network toxicology and molecular docking approach
利用网络毒理学和分子对接方法揭示氨甲环酸诱发癫痫的神经毒性机制
Tianyang ChenDalong LiuXiangYang Leng
Research 03 January 2026
Article: 67
Part of 1 collection: Epilepsy: Seizure prevention, treatment, and epidemiology
所属专题：癫痫：癫痫发作的预防、治疗和流行病学
Trop2 immuno-PET/CT imaging of prostate cancer: a proof-of-concept translational study
Trop2免疫正电子发射断层扫描/计算机断层扫描（PET/CT）成像在前列腺癌中的应用：一项概念验证性转化研究
Xingru LongShuxian AnDawei Jiang
Research 31 December 2025
Article: 66
Methylmalonate accumulation contributes to myocardial vulnerability post-reperfusion: a novel therapeutic target and prognostic biomarker
甲基丙二酸蓄积促进再灌注后心肌脆弱性：一种新型治疗靶点和预后生物标志物
Shanjie WangJunChen GuoShaohong Fang
Research 31 December 2025
Article: 65
Prophylactic effect of intraoperative sodium oxybate on postoperative delirium in older patients undergoing major orthopedic surgery: a randomized clinical trial
术中羟丁酸钠对接受大型骨科手术的老年患者术后谵妄的预防作用：一项随机临床试验
Meiying CuiHang XuePing Zhao
Research 31 December 2025
Article: 64
Part of 1 collection:Psychoactives: Recreational drugs repurposed as novel therapies
所属专题：精神活性物质：将娱乐性药物重新用于新型疗法
Prevalence of hysterectomy in urban China and associations between metabolic disorders and hysterectomy: a multicenter population-based study involving over 9 million women
中国城市子宫切除术的流行情况以及代谢紊乱与子宫切除术之间的关系：一项涉及超过900万女性的多中心人群基础研究
Yanrui BiYuan MaYing Gao
Research 30 December 2025
Article: 63
Sex differences in cardiac risk and kidney function: serum creatinine versus cystatin C
心脏风险和肾功能方面的性别差异：血清肌酐与胱抑素C的对比
Nicole L. De La MataJames A. HedleyJennifer S. Lees
Research 30 December 2025
Article: 62
The association of post-conization pregnancy with subsequent cervical lesions: evidence from a nationwide cohort in Sweden
锥切术后妊娠与后续宫颈病变的关联：来自瑞典全国队列研究的证据
Huan YiJimiao HuangJianguang Ji
Research 29 December 2025
Article: 61
Tibial periosteal distraction for ischemic leg ulcers: animal and clinical cohort study
胫骨骨膜牵张术治疗缺血性下肢溃疡：动物及临床队列研究
Peilin ZhouWenqiang WangQikai Hua
Research 28 December 2025
Article: 60
Preoperative conversion therapy of camrelizumab combined with paclitaxel and nedaplatin for unresectable advanced esophageal squamous cell carcinoma: a phase 2 study
卡瑞利珠单抗联合紫杉醇和奈达铂对不可切除的晚期食管鳞癌的术前转化治疗：一项2期研究
Jinhong ZhuJinfeng ZhangJianqun Ma
Research 28 December 2025
Article: 59
Clustering of cardiometabolic risk factors, physical activity, digital exclusion, and depressive symptoms trajectories in adults aged 50years and older: findings from two prospective cohort studies
50岁及以上成年人心血管代谢风险因素聚集、身体活动、数字排斥及抑郁症状轨迹：两项前瞻性队列研究的发现
Xiaosheng DongJiaqiang XiaoChengchao Zhou
Research 28 December 2025
Article: 58
Eligibility of real-world patients for aspirin primary prevention trials in cardiovascular disease
现实中符合心血管疾病阿司匹林一级预防试验资格的患者情况
Michael HolderDaniel R. MoralesBruce Guthrie
Research 27 January 2026
Article: 57
Polygenic risk score-guided personalized osteoporosis screening: a population-based study
基于多基因风险评分指导的个性化骨质疏松症筛查：一项基于人群的研究
Dongxue WangWen SunJianguang Ji
Research 14 January 2026
Article: 56
Urea cycle modulation by combined SGLT2 inhibitors and metformin
SGLT2抑制剂与二甲双胍联合用药对尿素循环的调节作用
Makoto HaradaJonathan AdamRui Wang-Sattler
Research 08 January 2026
Article: 55
Safety and neuroprotective efficacy of the VCP inhibitor ML240 in large-animal and human retinal explants: a preclinical ex vivo study
VCP抑制剂ML240在大型动物及人视网膜外植体中的安全性和神经保护功效：一项临床前离体研究
Ana-Cristina Almansa-GarcíaAngela ArmentoBlanca Arango-Gonzalez
Research 10 January 2026
Article: 54
Impact of an eight-week isocaloric vegan dietary intervention on hemogram parameters and lymphocyte subsets: a randomized-controlled trial
为期八周的等热量纯素饮食干预对血细胞参数和淋巴细胞亚群的影响：一项随机对照试验
Julian HerterFrieda StübingMaximilian Andreas Storz
Research 10 January 2026
Article: 53
Association between psychosocial factors and adverse effects of light-to-moderate ambient heat in patients with chronic diseases: results of the prospective cohort study CLIMATE-II
社会心理因素与轻至中度环境热对慢性病患者不良影响之间的关联：前瞻性队列研究CLIMATE-II的结果
Ingmar SchäferValentina PauckeDagmar Lühmann
Research 15 January 2026
Article: 52
Part of 1 collection:Climate change and human health
所属专题：气候变化与人类健康
Maternal infection during pregnancy and the risk of childhood cancer: a systematic review and meta-analysis
孕期母体感染与儿童期患癌风险：一项系统综述和荟萃分析
Loviisa MulanjeLara Kim BrackmannRajini Nagrani
Research 14 January 2026
Article: 51
Part of 1 collection:Carcinogens and human health
所属专题：致癌物与人类健康
Supplementary biomarker testing in molecular tumor boards increases actionable therapy recommendations: a prospective real-world study of 658 patients
分子肿瘤委员会中的补充生物标志物检测增加了可采取治疗措施的建议：一项针对658例患者的前瞻性真实世界研究
Alexander ScheiterSimon MellinKirsten Utpatel
Research 14 January 2026
Article: 50
Computer assisted verbal autopsy: comparing large language models to physicians for assigning causes to 6939 deaths in Sierra Leone from 2019–2022
计算机辅助口头尸检：对比大型语言模型与医生对塞拉利昂2019 - 2022年6939例死亡原因的判定
Richard WenAnteneh Tesfaye AssalifRashid Ansumana
Research 24 December 2025
Article: 49
Loss of Y chromosome and its implications in male amyotrophic lateral sclerosis: insights from the UK Biobank
Y染色体缺失及其在男性肌萎缩侧索硬化症中的影响：来自英国生物银行的研究见解
Wei-Ming SuQing-Qing DuanYong-Ping Chen
Research 24 December 2025
Article: 48
Part of 1 collection:Amyotrophic lateral sclerosis: latest advances and novel updates
所属专题：肌萎缩侧索硬化症：最新进展与新动态
Prenatal lipopolysaccharide exposure programs the early-life lung development by modulating mesenchymal fibroblasts in a time- and dose-dependent manner
产前脂多糖暴露通过调节间充质成纤维细胞以时间和剂量依赖性方式来影响早期肺部发育
Ying DongStefan HadzicSaverio Bellusci
Research 22 December 2025
Article: 47
Life course socioeconomic trajectories and chronic disease risk in later life among 30,055 older adults across 27 European countries (the SHARE study)
27个欧洲国家30,055名老年人生命历程中的社会经济轨迹与晚年慢性疾病风险（基于SHARE研究）
Taymara C. AbreuJoline W. J. BeulensJoreintje D. Mackenbach
Research 20 December 2025
Article: 46
Part of 1 collection:Healthy aging and longevity: the role of preventive medicine and risk factors
所属专题：健康老龄化与长寿：预防医学与风险因素的作用
Validation of a novel patient-reported measure of the burden of digital care in diabetes
由糖尿病患者报告的数字化护理负担新型测评工具的验证
Misk Al ZahidyJennifer L. RidgewayVictor M. Montori
Research 20 December 2025
Article: 45
Determinants of long-term SARS-CoV-2 immune responses in asymptomatic-to-moderate COVID-19 patients in sub-Saharan Africa
撒哈拉以南非洲地区无症状至中度 COVID-19 患者长期 SARS-CoV-2 免疫应答的决定因素
Víctor L. de RiojaOdin GoovaertsGemma Moncunill
Research 14 January 2026
Article: 44
Camrelizumab and apatinib in Chinese patients with locally advanced or metastatic radioiodine-refractory differentiated thyroid cancer: an exploratory open-label, single-arm trial
卡瑞利珠单抗联合阿帕替尼治疗中国局灶性晚期或转移性放射性碘难治性分化型甲状腺癌：一项探索性开放标签单臂试验
Xin ZhangDi SunYansong Lin
Research 18 December 2025
Article: 43
Urinary polyphenol signature of the Mediterranean diet is associated with lower cardiovascular disease risk: the PREDIMED trial
地中海饮食的尿液多酚特征与心血管疾病风险较低相关：PREDIMED 试验
Inés Domínguez-LópezPolina GalkinaRosa M. Lamuela-Raventós
Research 18 December 2025
Article: 42
Meta-analysis and external validation of a risk model for gastrointestinal bleeding after percutaneous coronary intervention
经皮冠状动脉介入治疗后胃肠道出血风险模型的荟萃分析及外部验证
Hualong MaCong PengQiaohong Yang
Research 18 December 2025
Article: 41
DNA methylation-based clocks, tobacco smoking, and lung cancer risk
基于DNA甲基化的生物钟、烟草吸烟与肺癌风险
Ricardo Cortez Cardoso PenhaJustina Ucheojor OnwukaMattias Johansson
Research 17 December 2025
Article: 40
Part of 1 collection:Carcinogens and human health
所属专题：致癌物与人类健康
Risk and protective factors associated with brain grey matter patterns in a population-based cohort of cognitively unimpaired 70years old
认知功能未受损的70岁老年人基于人口的队列中，与大脑灰质模式相关的风险和保护因素
Giulia LorenzonAnna MarsegliaEric Westman
Research 17 December 2025
Article: 39
Part of 1 collection:Healthy aging and longevity: the role of preventive medicine and risk factors
所属专题：健康老龄化与长寿：预防医学和风险因素的作用
Street view-derived city built environment and vulnerability to temperature extremes: a nationally representative population-based cohort study
基于街景图像的城市建成环境与极端温度脆弱性：一项全国代表性人口队列研究
Wanzhou WangChao YangLuxia Zhang
Research 16 December 2025
Article: 38
Part of 1 collection:Climate change and human health
所属专题：气候变化与人类健康
A booster dose of an inactivated SARS-CoV-2 vaccine targeting virus variants sustains protective humoral and cellular immunity
针对病毒变异株的灭活严重急性呼吸系统综合征冠状病毒2（SARS-CoV-2）疫苗加强针可维持保护性体液免疫和细胞免疫
Constanza MéndezLinmar Rodríguez-GuilarteSusan M. Bueno
Research 15 December 2025
Article: 37
Dapagliflozin alleviates sunitinib-induced cardiotoxicity through AMPKα-PPARα axis and enhances the sensitivity of renal cell carcinoma to sunitinib
达格列净通过AMPKα-PPARα轴减轻舒尼替尼诱导的心脏毒性，并增强肾细胞癌对舒尼替尼的敏感性
Shi-yu HuangMin HuLei Wang
Research 15 December 2025
Article: 36
Network dysfunction underlying verbal fluency deficits in newly diagnosed epilepsy: a resting-state fMRI functional connectivity study
新诊断癫痫患者言语流畅性缺陷背后的网络功能障碍：一项静息态功能磁共振成像功能连接研究
Fangzhou LiuPing JiangLing Liu
Research 13 December 2025
Article: 35
Part of 1 collection:Epilepsy: Seizure prevention, treatment, and epidemiology
所属专题：癫痫：癫痫发作的预防、治疗和流行病学
Long-term quality of life in non-epithelial ovarian cancer survivors: TMRG-GINECO-Vivrovaire rare tumors case–control study
基于广西新生儿地中海贫血基因组图谱计划开展的家庭三联体/四联体分析
Coraline DubotIsabelle Ray-CoquardFlorence Joly
Research 12 December 2025
Article: 34
Family trios/quartets analysis based on the Newborn Genomic Atlas for Thalassemia project in Guangxi
非上皮性卵巢癌幸存者的长期生活质量：TMRG-GINECO-Vivrovaire罕见肿瘤病例对照研究
Wei WeiChunrong GuiBaoheng Gui
Research 12 December 2025
Article: 33
Hyperuricemic persons use more analgesics than normouricemic—is asymptomatic hyperuricemia really asymptomatic?
高尿酸血症患者比血尿酸正常者使用更多镇痛药——无症状性高尿酸血症真的“无症状”吗？
Janis TimsansJenni Emilia KauppiMarkku Kauppi
Research 11 December 2025
Article: 32
Social isolation, loneliness, and multi-system medical conditions: phenome-wide association and disease-trajectory analyses
社会孤立、孤独感与多系统医学病症：全表型组关联分析及疾病轨迹研究
Tingshan DuanZhi CaoChenjie Xu
Research 10 December 2025
Article: 31
Digital marketing techniques within online food retail platforms: a scoping review
在线食品零售平台中的数字营销技巧：一项范围综述
Adyya GuptaCatherine E. HugginsAnna Peeters
Research 10 December 2025
Article: 30
Dramatic increases in redundant publications in the Generative AI era
生成式人工智能时代冗余出版物数量急剧增加
Danny MaupinTulsi SuchakMatt Spick
Research 09 December 2025
Article: 29
Cardiovascular risk burden and guideline-recommended lipid and blood pressure goals in an Italian Cohort: findings from the HUMTELEMED web-based platform
意大利人群心血管风险负担及指南推荐的血脂和血压目标达成情况：HUMTELEMED网络平台的发现
Matteo LandolfoAlessandro GezziRiccardo Sarzani
Research 09 December 2025
Article: 28
Part of 1 collection:Healthy aging and longevity: the role of preventive medicine and risk factors
所属专题：健康老龄化与长寿：预防医学及风险因素的作用
Efficacy and safety of Janus kinase 1/2 inhibitor KL130008 in active rheumatoid arthritis: a randomized, double-blind, placebo-controlled phase II trial
Janus激酶1/2抑制剂KL130008治疗活动性类风湿关节炎的有效性和安全性：一项随机、双盲、安慰剂对照的II期试验
Yue ChengHonghu TangYi Liu
Research 09 December 2025
Article: 27
Risk stratification for endometrial cancer: independent and joint effects of polygenic risk score and body mass index in 129,829 UK Biobank participants
子宫内膜癌的风险分层：英国生物银行129,829名参与者中多基因风险评分和体重指数的独立及联合效应
Xuemin WangLaure DossusTracy A. O’Mara
Research 10 February 2026
Article: 26
Maternal probiotics intake during pregnancy and exclusive colostrum breastfeeding are associated with a reduced risk of neonatal jaundice
孕期摄入益生菌及纯母乳喂养初乳与新生儿黄疸风险降低相关
Bekalu Kassie AlemuChi Chiu WangYao Wang
Research 08 December 2025
Article: 25
Hepatic steatosis in postmenopausal women is characterized by distinct serum extracellular vesicle proteomic signatures
绝经后女性脂肪肝具有独特的血清细胞外囊泡蛋白质组特征
Patrick PirrotteBrooke LovellJohanna K. DiStefano
Research 07 December 2025
Article: 24
Global, regional, and national temporal trends in the prevalence of environmental heat and cold exposure among older adults aged 60–99 years, 1990–2021: an age-period-cohort analysis based on the Global Burden of Disease Study 2021
基于2021年全球疾病负担研究，对1990 - 2021年60 - 99岁老年人环境热暴露和冷暴露患病率的全球、区域和国家时间趋势分析：一项基于年龄 - 时期 - 队列模型的分析
Shenghao XuJing WangJianlin Xiao
Research 07 December 2025
Article: 23
Part of 1 collection:Climate change and human health
所属专题：气候变化与人类健康
Cyclophilin B deficiency enhances myocardial energy synthesis and protects against heart failure in preclinical models
亲环蛋白B缺乏可增强心肌能量合成，并在临床前模型中预防心力衰竭
Xiao ZongXierenayi TudiRong Tao
Research 07 December 2025
Article: 22
Part of 1 collection:Cardiomyopathy and cardiac arrhythmias
所属专题：心肌病与心律失常
Normobaric hyperoxia for intracerebral hemorrhage: a randomized clinical trial
常压高氧治疗脑出血：一项随机临床试验
Zhiying ChenJiayue DingRan Meng
Research 07 December 2025
Article: 21
Nationwide trends in pediatric hospitalizations for eating disorders in France between 2013 and 2022: a retrospective study using the national health insurance database
Emmanuelle LogeaisFrançoise TroussierLilia Khendek
2013 - 2022年法国因进食障碍住院的儿科患者全国趋势：一项使用国家健康保险数据库的回顾性研究
Research 05 December 2025
Article: 20
Part of 1 collection:Child and adolescent psychiatry
所属专题：儿童与青少年精神病学
Self-management of vaginal pessaries for pelvic organ prolapse: multi-method process evaluation, linked to the TOPSY randomised controlled trial
盆腔器官脱垂阴道子宫托自我管理：与TOPSY随机对照试验相关的多方法过程评估
Carol BuggeMelanie Dembinskythe TOPSY team
Research 05 December 2025
Article: 19
Large-scale plasma proteomics reveals bidirectional associations between sleep patterns and inflammatory bowel disease: a prospective cohort study
大规模血浆蛋白质组学研究揭示睡眠模式与炎症性肠病之间的双向关联：一项前瞻性队列研究
Kaixing LeYaru LiuZhigang Liu
Research 05 December 2025
Article: 18
Association between socioeconomic status and diabetic retinopathy in individuals with type 1 diabetes: a systematic review and meta-analysis
1型糖尿病患者社会经济地位与糖尿病视网膜病变之间的关联：一项系统综述和荟萃分析
Fernando Sebastian-VallesSergio Núñez de Arenas-ArroyoJulia Martínez-Alfonso
Review 05 December 2025
Article: 17
Patterns of disparity: age and socioeconomic differences in women’s smoking and quitting outcomes in Great Britain
差异模式：英国女性吸烟及戒烟结局的年龄和社会经济差异
Sarah E. JacksonCaitlin NotleySharon Cox
Research 10 February 2026
Article: 16
Genomic pathogenic alterations in the SWI/SNF complex compromise the outcomes of immunotherapy in Chinese patients with KRAS-mutant NSCLC by downregulating STING expression
SWI/SNF复合体中的基因组致病性改变通过下调STING表达损害中国KRAS突变型非小细胞肺癌患者的免疫治疗效果
Lingling GaoJie JiangXuchao Zhang
Research 03 December 2025
Article: 15
Residential radon exposure and incident myocardial infarction and stroke risks in the All of Us Research Program
“我们所有人”研究项目中住宅氡暴露与心肌梗死和卒中发病风险的关系
Jiajun LuoZhihao JinBriseis Aschebrook-Kilfoy
Research 03 December 2025
Article: 14
Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) diet and cardiovascular disease and arrhythmias
用于延缓神经退行性变的地中海饮食-终止高血压膳食疗法干预措施（MIND）与心血管疾病及心律失常的关系
Pei QinFrederick K. HoJill P. Pell
Research02 December 2025
Article: 13
Part of 1 collection: Cardiomyopathy and cardiac arrhythmias
所属专题：心肌病与心律失常
KoMethylNet: a novel epigenetic clock based on neural network analysis of DNA methylation data and epigenetic age acceleration in a Korean population
KoMethylNet：基于神经网络分析DNA甲基化数据的新型表观遗传时钟及韩国人群的表观遗传年龄加速研究
Dabin YunKwangyeon OhNan Song
Research 03 December 2025
Article: 12
Part of 1 collection: Healthy aging and longevity: the role of preventive medicine and risk factors
所属专题：健康老龄化与长寿：预防医学及风险因素的作用
Sleep and physical activity trade-offs and dementia risk: a prospective cohort study in UK Biobank participants
睡眠与体力活动的权衡与痴呆风险：英国生物样本库参与者的一项前瞻性队列研究
Stephanie YiallourouLachlan CribbMatthew P. Pase
Research 03 December 2025
Article: 11
Part of 1 collection: Sleep and mental health
所属专题：睡眠与心理健康
Integration of gut microbiome and lipid metabolism reveals the anti-cancer effects of pentadecanoic acid on bladder cancer
肠道微生物组与脂质代谢的整合揭示十五烷酸对膀胱癌的抗癌作用
Ya-Ting ChenJing SuiEvan Yi-Wen Yu
Research 03 December 2025
Article: 10
Part of 1 collection: Gut microbiota: New treatments of human disease
所属专题：肠道微生物群：人类疾病的新疗法
A social determinants-based county-level cardiovascular mortality index to identify high-risk counties in the USA
基于社会决定因素的美国县级心血管疾病死亡率指数，用于识别高风险县
Anqi ZhuBibhas ChakrabortyTazeen H. Jafar
Research 02 December 2025
Article: 9
HIV infection and immunosenescence: challenges and intervention strategies
HIV感染与免疫衰老：挑战与干预策略
Junyan JinQianqian XuBin Su
Review 02 December 2025
Article: 8
Part of 1 collection: Healthy aging and longevity: the role of preventive medicine and risk factors
所属专题：健康老龄化与长寿：预防医学与风险因素的作用
Machine learning-based prediction of short-term outcomes in aneurysmal subarachnoid hemorrhage: a multicenter study integrating clinical and inflammatory indicators
基于机器学习的动脉瘤性蛛网膜下腔出血短期预后预测：一项整合临床与炎症指标的多中心研究
Weichong ZhouCong PengHui Shi
Research 29 November 2025
Article: 7
The effectiveness and safety of a mobile application-based self-regulation intervention to support weight loss among adults living with obesity: a large-scale pragmatic randomised controlled trial
基于移动应用程序的自我调节干预措施在支持肥胖成年人减重方面的有效性与安全性：一项大规模实用性随机对照试验
Paul DoodyGina M. WrenPaul Aveyard
Research 29 November 2025
Article: 6
Part of 1 collection: Weight loss interventions and their health impacts
所属专题：减重干预措施及其对健康的影响
Adiposity and the first-onset of diagnosed mental illnesses: a population-based cohort study of 10 million UK adults
脂肪堆积（肥胖程度）与首次确诊精神疾病的关系：一项基于1000万英国成年人的队列研究
Xue DongPaul AveyardMin Gao
Research 29 November 2025
Article: 5
Efficacy of standard care versus acoustic therapy on acute tinnitus in idiopathic sudden sensorineural hearing loss: a randomized controlled trial
标准治疗与声治疗对特发性突发性感音神经性听力损失伴急性耳鸣的疗效对比：一项随机对照试验
Xinyi WangKe QiuYu Zhao
Research 28 November 2025
Article: 4
Trends and socio-economic inequalities in overweight- and obesity-related premature cardiovascular disease mortality in Australia
澳大利亚超重与肥胖相关过早心血管疾病死亡的趋势及社会经济不平等状况
Tim Adair
Research 29 January 2026
Article: 3
Assessing the impact of maternal blood pressure during pregnancy on perinatal health: a wide-angled Mendelian randomization study
评估孕期母体血压对围产期健康的影响：一项广角孟德尔随机化研究
Fernanda Morales-BersteinAna Gonçalves-SoaresMaria-Carolina Borges
Research 14 January 2026
Article: 2
Part of 1 collection:Diagnosis and management of gestational diabetes
所属专题：妊娠期糖尿病的诊断与管理
Prevalence of use and interest in using glucagon-like peptide-1 receptor agonists for weight loss: a population study in Great Britain
胰高血糖素样肽-1受体激动剂用于减重的使用率及使用意愿：一项针对英国人群的研究
Sarah E. JacksonJamie BrownLion Shahab
Research 08 January 2026
Article: 1
Part of 1 collection: Weight loss interventions and their health impacts
所属专题：减重干预措施及其对健康的影响
2026-06-30
还在为肾癌免疫治疗响应率低而发愁？这篇Frontiers综述带你穿透ccRCC免疫检查点阻断的迷雾：从PBRM1突变、TME空间异质性，到单细胞+空间转录组+AI多模态解码，连OXPHOS代谢重编程如何“窒息”CD8+ T细胞都讲得明明白白——机制、数据、临床转化全链条拆解！
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新鲜出炉！今天给大家深度剖析一篇2026年5月12日发表在《Frontiers in Immunology》上的文章，题目为：解析透明细胞肾细胞癌中免疫检查点阻断的作用机制图景：从分子驱动因素到治疗反应
Deciphering the mechanistic landscape of immune checkpoint blockade in ccRCC: from molecular drivers to therapeutic responses.
本研究是一篇系统性综述，全面总结了透明细胞肾细胞癌（ccRCC）中免疫检查点抑制剂（ICI）疗效与耐药性的多层次生物学机制，重点阐述了肿瘤内在驱动因素、免疫抑制性肿瘤微环境（TME）、多组学技术解析及人工智能（AI）赋能的精准免疫治疗新范式。
影响因子：5.9
发表期刊：Frontiers in Immunology
团队成员合影（位于上海陆家嘴中心，可随时预约参观）
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CNSknowall 平台 Pubmed+AI 快速提炼研究亮点·研究思路·研究结果·研究结论
研究亮点
1.聚焦核心临床瓶颈： 系统梳理了ICI在ccRCC中广泛应用背景下仍面临的原发性与获得性耐药这一关键挑战，明确指出其根源在于肿瘤内在因素与免疫抑制性TME的复杂互作。
2.整合多维耐药机制： 不仅涵盖经典PD-1/PD-L1、CTLA-4通路，还深入解析了LAG-3、TIGIT、TIM-3、HHLA2/KIR3DL3等新兴免疫检查点，以及PBRM1基因突变/剪接异常、OXPHOS代谢重编程、TME空间结构（如TLS、CAF-肿瘤细胞互作）等多维度耐药驱动因素。
3.强调TME动态性与异质性： 指出TME并非静态背景，其分子亚型（血管/基质型 vs 效应T细胞/增殖型）、特定免疫细胞亚群功能状态（如NKG2A+CD8+ T细胞、IL1B+ Treg、APOE+ M2样巨噬细胞）、物理屏障（异常血管、ECM）及生化特性（缺氧、代谢物积累）共同塑造了ICI疗效。
4.前沿技术深度赋能： 全面评述了单细胞RNA测序（scRNA-seq）、空间转录组学、ATAC-seq、蛋白质组学、代谢组学等多组学技术如何从细胞组成、空间定位、表观遗传、功能输出等层面，系统揭示ccRCC对ICI响应与抵抗的深层机制。
5.AI驱动精准免疫新路径： 重点论述了AI在病理图像（pathomics）、医学影像（radiomics）分析及多组学数据整合中的核心作用，展示了其在非侵入性预测疗效、发现新型生物标志物、指导个体化治疗及加速药物研发方面的巨大潜力。
核心创新点
1.提出“机制-技术-临床”闭环框架： 将ccRCC ICI耐药的分子与微环境机制，与单细胞/空间多组学解析技术、AI建模能力紧密结合，构建了一个从基础发现到临床转化的完整逻辑链条。
2.深化对TME空间架构的理解： 强调空间转录组学揭示的TME内细胞空间分布模式（如单核细胞包裹耗竭CD8+ T细胞、TLS的空间位置与成熟度）是决定ICI疗效的关键，超越了单纯细胞数量的评估。
3.确立代谢重编程的核心地位： 明确将肿瘤细胞高活性氧化磷酸化（OXPHOS）作为关键耐药机制，阐明其通过加剧TME缺氧进而抑制CD8+ T细胞功能的因果链条，并指出靶向OXPHOS是增强联合免疫治疗的有效策略。
4.推动AI从辅助工具到决策核心： 提出AI不仅是处理海量数据的工具，更是连接病理、影像、基因组、临床数据的“翻译器”，其构建的可解释模型（如COMPASS）有望直接指导临床治疗决策。
5.倡导液体活检动态监测： 突出循环生物标志物（如sTIM-3、Kyn/Trp比值、KIM-1、sPD-L1/sPD-1）在实时、无创监测治疗反应与耐药发生中的应用前景，为动态调整治疗方案提供依据。
研究背景
透明细胞肾细胞癌（ccRCC）是肾细胞癌中最主要的亚型。尽管以PD-1/PD-L1、CTLA-4为靶点的免疫检查点抑制剂（ICI）及其联合疗法已彻底改变了晚期ccRCC的治疗格局，显著改善了患者生存，但仍有相当比例的患者存在原发性或获得性耐药，导致治疗失败。这种疗效的高度异质性提示，ICI的作用效果受到肿瘤自身分子特征与所处免疫微环境（TME）的共同调控，亟需系统性地解析其背后的复杂机制。
研究思路
1.机制梳理： 系统回顾并整合现有文献，从肿瘤细胞内在驱动因素（如PBRM1、BAP1等基因突变）、TME的免疫抑制性构成（如Treg、MDSC、TAM、CAF）、代谢重编程（如OXPHOS、缺氧）及新兴免疫检查点等多个层面，阐明ICI耐药的生物学基础。
2.技术解析： 评述多组学技术（单细胞/空间转录组、表观基因组、蛋白组、代谢组）在刻画ccRCC TME异质性、识别关键细胞亚群、解析细胞间通讯及发现新靶点方面的应用与进展。
3.AI赋能： 分析人工智能（AI）如何利用病理图像（WSI）、医学影像（CT/MRI）及多组学数据，构建预测模型，用于疗效预判、生物标志物挖掘及个体化治疗方案制定。
4.临床转化： 结合关键III期临床试验（如CheckMate 214, KEYNOTE-426, CLEAR）数据，讨论不同ICI组合（ICI-ICI, ICI-TKI）在不同风险分层患者中的疗效与安全性，并展望新型治疗策略（如三联疗法、靶向新检查点、CAR-T、肿瘤疫苗）及围手术期免疫治疗的应用。
研究结果
1.ICI作用机制： ICI通过阻断PD-1/PD-L1、CTLA-4等抑制性信号通路，恢复T细胞抗肿瘤功能；同时，LAG-3、TIGIT、TIM-3、HHLA2/KIR3DL3等新兴检查点也参与T细胞耗竭，是克服耐药的新靶点。
2.耐药机制： 肿瘤内在因素包括PBRM1基因突变/异常剪接、PTPRZ1表达、内源性逆转录病毒（ERV）表达模式等；TME因素包括免疫抑制性细胞浸润（Treg、MDSC、APOE+ TAM）、空间结构异常（TLS缺失、CAF包裹）、代谢紊乱（OXPHOS升高导致缺氧）及系统性因素（肌脂肪萎缩）。
3.多组学发现： scRNA-seq鉴定出APOE+ M2样巨噬细胞、NKG2A+CD8+ T细胞等关键耐药相关亚群；空间转录组揭示了TME内细胞的空间互作模式；ATAC-seq等表观组学技术识别了调控基因表达的非编码元件；代谢组学发现Kyn/Trp比值升高等与不良预后相关。
4.AI应用进展： AI模型已能基于H&E染色切片预测ccRCC患者生存及ICI疗效；基于CT影像的放射组学特征可早期识别ICI无应答者；AI驱动的多组学整合模型（如COMPASS）正尝试将肿瘤转录组映射至可解释的免疫生物学概念，以预测治疗反应。
5.临床证据： ICI-ICI（纳武利尤单抗+伊匹木单抗）和ICI-TKI（帕博利珠单抗+阿昔替尼/仑伐替尼）组合已成为一线标准；辅助帕博利珠单抗在KEYNOTE-564研究中证实可改善高危ccRCC患者的无病生存期（DFS）和总生存期（OS）；而新辅助ICI单药疗效有限，三联疗法（COSMIC-313）虽改善无进展生存期（PFS）但未延长OS且毒性增加。
研究结论与讨论
结论：ccRCC对ICI的响应与耐药是一个由肿瘤细胞内在遗传/表观遗传改变与高度异质、动态演化的免疫抑制性TME共同决定的复杂过程。未来突破的关键在于：第一，利用单细胞与空间多组学技术，超越“细胞类型”的简单分类，深入解析TME中各类细胞的功能状态、空间邻域关系及代谢-免疫互作网络；第二，将AI作为核心引擎，整合病理、影像、分子与临床数据，构建真正可泛化、可解释的预测模型，实现从经验性治疗向精准免疫治疗的范式转变；第三，基于上述机制认知，理性设计靶向特定耐药通路（如OXPHOS、HHLA2、TIM-3）或重塑TME（如靶向CAF、促进TLS形成）的新型联合策略。
具体研究结果
1 ICIs在ccRCC中的作用机制
ICIs的成功应用源于对肿瘤免疫逃逸机制的深入理解；这些药物通过重新激活宿主免疫系统以对抗癌症（37, 38）。ICIs主要通过阻断肿瘤细胞利用以逃避免疫清除的抑制性检查点通路发挥作用，其中经典的PD-1/PD-L1和CTLA-4轴是当前治疗的核心靶点（11, 19, 22, 24）。PD-1主要表达于活化T细胞、B细胞和自然杀伤（NK）细胞表面，而其配体PD-L1和PD-L2则广泛表达于多种细胞类型，包括肿瘤细胞和抗原呈递细胞（APCs）（39–44）。PD-L1与PD-1结合可抑制T细胞增殖、活化及细胞因子产生，导致T细胞耗竭，使肿瘤细胞逃避免疫监视（39, 41）。相比之下，CTLA-4主要在T细胞活化的早期阶段发挥负调控作用。它与CD28竞争结合B7分子（CD80/CD86），从而抑制T细胞的初始活化和增殖（11, 19, 22, 24）。因此，抗PD-1/PD-L1抗体通过破坏PD-1/PD-L1信号通路恢复T细胞的细胞毒功能，而抗CTLA-4抗体主要增强淋巴器官内T细胞的启动和活化（19, 22, 24, 39–42）。然而，RCC对ICIs反应的异质性及耐药性的普遍存在表明，免疫逃逸机制远为复杂。近年来，对RCC肿瘤微环境（TME）动态调控、肿瘤代谢重编程及肿瘤细胞内在逃逸通路的研究揭示了影响ICI疗效的其他生物学机制和潜在治疗靶点（45, 46）。
1.1 新兴免疫检查点及通路
随着对PD-1/PD-L1和CTLA-4通路认识的深入以及耐药挑战日益明显，研究者已将焦点转向其他靶点，常被称为“下一代”免疫检查点分子。LAG-3、TIGIT和TIM-3等新型检查点常与PD-1共表达于耗竭T细胞上，导致其功能障碍（47）。因此，靶向这些分子，尤其是与PD-1/PD-L1抑制剂联合使用，已成为一种具有生物学合理性和前景的策略，以克服当前免疫治疗的耐药性，尽管其在ccRCC中的临床获益仍有待充分证实。例如，LAG-3抑制剂relatlimab联合nivolumab已被批准用于黑色素瘤治疗，展示了其潜力（48, 49）。具体而言，LAG-3通过抑制T细胞增殖和功能下调免疫反应；在RCC中，其表达与高危患者的免疫治疗反应和生存改善相关（47）。TIGIT通过竞争性结合其配体（如CD155）抑制T细胞和NK细胞的活化，从而削弱免疫反应（50）；在RCC肿瘤组织中已观察到TIGIT的高表达（51）。TIM-3通过与其配体Galectin-9相互作用诱导Th1细胞耗竭并促进免疫耐受。RCC中也观察到TIM-3表达升高，靶向TIM-3有望恢复T细胞功能（52, 53）。此外，主要在髓系细胞上表达的抑制性受体，如免疫球蛋白样转录物4（ILT4），正被探索作为治疗靶点。ILT4通过与MHC I类分子相互作用促进免疫抑制性TME（54），其抑制剂在晚期实体瘤中已显示出初步抗肿瘤活性（55）。这些新兴免疫检查点分子及其通路如图1所示。
一个显著的例子是HHLA2（B7-H7）/KIR3DL3轴。HHLA2（HERV-H LTR-associating protein 2），又称B7-H7，是B7配体家族成员，在免疫调节中表现出复杂的双重
FIGURE 1 Mechanisms of immune checkpoint inhibitors (ICIs) in clear cell renal cell carcinoma (ccRCC). The signaling of immune checkpoint inhibitors (ICIs) is intricately regulated through interactions among various cells, including RCC tumor cells, T cells, macrophages, and dendritic cells. RCC tumor cells present tumor peptides to T cells via major histocompatibility complex (MHC) glycoproteins, engaging the T cell receptor (TCR). Key inhibitory interactions occur as PD-L1/2, CD80/CD86, CD115, and FGL1 on RCC tumor cells bind with PD-1, CD28/CTLA-4, TIGIT, and LAG3 on T cells, respectively; notably, HHLA2 on tumor cells interacts with KIR3DL3 on T cells. Additionally, RCC tumor cell-expressed GAL-9 and MHC1 interact with TIM3 on macrophages and ILT4 on dendritic cells, modulating immune responses. By blocking these inhibitory pathways, ICIs restore T cell function, enhance tumor cell recognition, and bolster anti-tumor immunity.
作用。KIR3DL3是一种主要表达于T细胞和NK细胞上的抑制性受体，最近被确定为HHLA2的关键功能性受体（56）。Bhatt等人的研究表明，在ccRCC中，HHLA2和PD-L1的表达通常不重叠，提示HHLA2可能通过独立于PD-1/PD-L1信号通路的途径介导免疫逃逸。当肿瘤细胞表面的HHLA2与免疫细胞上的KIR3DL3结合时，通过其ITIM基序招募SHP-1/SHP-2磷酸酶。这种招募抑制了包括Vav1、ERK、AKT和NF- κ B在内的下游信号通路，导致CD8+ T细胞和NK细胞功能的全面抑制（56, 57）。目前正在进行一项与HCRN GU16–260试验相关的研究，评估HHLA2和PD-L1联合表达作为ccRCC患者ICI治疗预测性生物标志物的潜力（58）。此外，肿瘤细胞内在的表观遗传失调为理解耐药机制和识别新靶点提供了进一步线索。例如，Chung等人发现，在获得性ICI耐药的RCC中，PD-L1信号通路激活了“SOX10→MITF→GPNMB”级联反应（59），而CTLA4基因启动子的低甲基化状态与ICI疗效相关（20）。然而，近期临床数据显示，并非所有新兴检查点策略都能在ccRCC中转化为更优疗效。在ESMO 2025会议上公布的KEYMAKER-U03亚组研究中，基于LAG-3和TIGIT的试验组未优于pembrolizumab联合lenvatinib对照组，表明在某些患者中，其他耐药机制可能是更重要的治疗靶点（60）。这些机制的复杂性和多样性凸显了个体化治疗策略的必要性。
1.2 肿瘤微环境（TME）的动态调控
ICIs的临床成功深受复杂TME动态调控的影响。传统上，肿瘤浸润淋巴细胞（TILs）的数量，尤其是CD8+ T细胞，被视为评估抗肿瘤免疫反应和预测ICI疗效的关键指标（61, 62）。然而，TME中还广泛存在调节性T细胞（Tregs）和髓源性抑制细胞（MDSCs）等免疫抑制性细胞类型，它们通过多种机制抑制T细胞活化并促进免疫耐受，从而显著限制ICI的治疗效果（63–65）。
对RCC（尤其是ccRCC）TME的近期深入研究表明其复杂性和高度异质性。首先，RCC TME表现出显著的分子异质性，可将其分为不同的分子亚型，如血管/基质型和T效应/增殖型。这些亚型具有独特的免疫细胞浸润模式和微环境组分，与患者对ICI的反应密切相关（66）。其次，特定免疫细胞亚群的“质量”和功能状态可能比其数量对ICI疗效更为关键。例如，NKG2A(+)CD8(+) T细胞亚群的浸润与免疫抑制性微环境和较差的ICI治疗反应相关（23）。同时，在ccRCC中鉴定出的表达IL1B的
Treg亚群可能在TME中发挥关键的免疫抑制作用（30），而效应T细胞相关标志物的表达模式（如PD-1/CD8和CD39/CD3比率）也是重要的预后因素（67）。此外，TME中的基质成分，如癌相关成纤维细胞（CAFs）和内皮细胞（ECs），在ccRCC微环境中表现出显著的亚簇异质性和独特的空间分布模式。它们与免疫细胞的空间互作共同塑造了TME的整体功能（30）。最后，TME的理化特性，如RCC微环境中普遍存在的缺氧状态，已被证明可直接损害肿瘤浸润CD8+ T细胞的细胞毒功能；克服这种缺氧可能增强其抗肿瘤活性（68, 69）。肿瘤自身的空间生长模式（例如，表浅性与体积性生长）也构建了独特的微环境结构，进而影响克隆多样性和细胞间相互作用（70）。
免疫细胞亚群的复杂互作和功能重编程密切相关。在RCC TME内，多种免疫抑制性细胞亚群与效应T细胞相互作用，共同建立免疫抑制状态。例如，肿瘤相关巨噬细胞（TAMs）、MDSCs和Tregs是ICI原发性和获得性耐药的关键贡献者（64, 71）。这些细胞通过多种机制抑制效应T细胞功能，包括分泌抑制性细胞因子（如IL-10和TGF- β ）、表达免疫检查点配体（如PD-L1）以及消耗T细胞活化所需的必需氨基酸（如精氨酸）（72–74）。例如，TME中TAMs的富集通过降低T细胞和NK细胞活性、表达PD-L1以及释放可溶性免疫抑制因子促进ICI耐药（75）。进一步研究揭示了TAMs的异质性及其代谢状态对其功能的影响；例如，TAMs中增强的糖酵解产生乳酸，可驱动其向M2（促肿瘤）表型极化（76, 77）。此外，在接受ICI治疗的RCC患者中，疾病进展患者的外周血中表达GPNMB的单核MDSCs（M-MDSCs）频率显著高于应答者，提示特定MDSC亚群可能与ICI耐药密切相关（59）。
异常的肿瘤血管生成和重塑的细胞外基质（ECM）也对ICI疗效构成显著障碍。VEGF通路不仅驱动肿瘤血管生成，还促进免疫抑制性微环境的形成。因此，将ICIs与抗VEGF药物联合可“正常化”肿瘤血管，从而改善TME的灌注和氧合，并促进T细胞浸润（78–80）。在ccRCC中，间质样肿瘤细胞与一种特定CAF亚型（即肌成纤维细胞样CAFs，myCAFs）的空间互作与ICI耐药相关。这些CAFs通过创建物理和化学屏障限制免疫细胞浸润，从而促进耐药（81–83）。
代谢因素不容忽视，因为肿瘤细胞的代谢重编程不仅支持其生长，还深刻影响
TME内免疫细胞的功能。近期研究强调了氧化磷酸化（OXPHOS）在RCC ICI耐药中的核心作用。通过分析包括CheckMate、JAVELIN Renal 101和NCT01358721在内的多项临床试验数据以及同济医院25例患者的临床病理数据，Tian等人发现，肿瘤组织（尤其是转移灶）中高水平的OXPHOS是ICI耐药的重要风险因素，与RCC患者较短的PFS和OS相关（68）。机制上，具有活跃OXPHOS的RCC细胞从TME中大量消耗氧气，加剧缺氧，进而抑制效应T细胞功能并可能诱导T细胞耗竭（68）。临床前研究证实，抑制肿瘤细胞OXPHOS可改善TME的免疫抑制状态并增强CD8+ T细胞功能，从而提高抗PD-L1治疗的疗效（68）。
2 ccRCC中ICIs的耐药性
尽管ICIs显著改善了ccRCC的治疗结局，但获得性或原发性耐药仍是限制其疗效的关键挑战（84）。深入理解驱动耐药的分子机制和TME特征对于指导临床实践和开发新型治疗策略至关重要（85）。近期研究在此基础上进一步揭示了更深层次的耐药机制。
肿瘤细胞内在的遗传改变是异质性反应和ICI耐药的重要促成因素。PBRM1基因改变是ccRCC中的常见突变，与肿瘤-免疫相互作用和免疫治疗结局相关，但已发表的研究结果存在矛盾，提示其作用具有情境依赖性（86, 87）。Cho等人的研究进一步揭示，PBRM1基因的异常选择性剪接（特别是RBFOX2介导的外显子26至外显子27剪接变体减少）与ICI疗效降低相关，为PBRM1在此背景下的作用提供了新视角（86）。此外，Fan等人表明，CDC20介导的PBRM1选择性自噬降解可能影响RCC的免疫治疗效果（88）。近期证据进一步提示，PBRM1突变与免疫治疗获益的关联可能取决于代谢亚型，为这些不一致的发现提供了潜在解释（89）。除PBRM1外，其他基因的改变也参与耐药过程。Lu等人发现，内源性逆转录病毒（ERVs）的表达模式与ICI疗效相关，可作为预测指标（90）。Ma等人的研究表明，PTPRZ1可能通过去磷酸化并稳定RNF26来降低ccRCC中TKIs和PD-1阻断的疗效（12）。
TME的复杂性和免疫抑制状态是决定ICI疗效的关键因素。疾病进展常伴随TME向免疫抑制表型的演变。Song等人利用单细胞和空间转录组学揭示了ccRCC TME的高度异质性，并鉴定出SPP1–CD44信号通路可能是免疫治疗原发性耐药的潜在驱动因素（30）。Qiu等人发现，肿瘤内NKG2A+CD8+
T细胞的浸润与ccRCC患者的不良预后和免疫治疗耐药相关；这些细胞表现出检查点分子的高表达和效应功能受损（23）。Li等人的研究表明，TUBA1C可能通过协调免疫抑制性TME介导免疫检查点阻断耐药（91）。代谢失调是TME内免疫抑制的另一主要驱动因素。Tian等人提出，靶向氧化磷酸化（OXPHOS）可增强肾癌联合免疫治疗的疗效；例如，Ndufb8敲低可减轻肿瘤浸润CD8+ T细胞的缺氧暴露并增强其细胞毒能力（68）。Zhu等人探索了使用纳米颗粒递送的HIF-2α抑制剂靶向缺氧并抑制自噬，从而增强治疗效果的潜力（69）。系统性因素如肌脂质浸润也被Yu等人发现对转移性RCC患者的ICI反应具有复杂甚至矛盾的影响（92）。在循环中，Pourmir等人提出血清或血浆中可溶性TIM-3水平可预测ICI耐药（93）。Kato等人的研究表明，外周T细胞受体库的特征可预测抗PD-1单药治疗的持久反应（67）。Hwang等人也探索了循环免疫生物标志物与转移性RCC患者免疫治疗反应的相关性（94）。
针对这些耐药机制，多种策略正在积极探索中。除广泛使用的ICIs与抗血管生成TKIs联合外，新型联合治疗模式旨在克服TME介导的免疫抑制和适应性肿瘤逃逸（95）。这些策略包括靶向TIM-3和TIGIT等新免疫检查点，以及将ICIs与其他免疫调节剂、双特异性抗体、CAR-T细胞疗法、治疗性疫苗或细胞因子联合（96）。例如，Liu等人研究了阿昔替尼和PD-L1 siRNA的共递送，以实现血管正常化和免疫检查点抑制的协同效应（97）。Msaouel等人领导的一项I期试验已发表，评估了sitravatinib（一种靶向TAM受体的多激酶TKI）联合nivolumab和ipilimumab在晚期ccRCC中的应用；这些早期阶段数据主要提供可行性和安全性信息，而非确定性疗效（98）。Wu等人的研究表明，cabozantinib与mTORC1/2抑制剂sapanisertib联合可有效阻断多种耐药机制（99）。对于既往ICI治疗后疾病进展的患者，后续治疗选择包括挽救性ICI联合治疗（如nivolumab联合ipilimumab）或转换为靶向药物如belzutifan或everolimus（84, 100）。
此外，在早期阶段，辅助pembrolizumab基于KEYNOTE-564试验证实的疗效和生存获益，已确立为新的护理标准（101）。与此形成鲜明对比的是，其他基于ICI的策略并未取得类似成功；具体而言，围手术期nivolumab（PROSPER）和辅助nivolumab联合ipilimumab（CheckMate 914）均报告了阴性结果，未能达到其主要无病生存期（DFS）终点（84, 102）。因此，基于对耐药机制的深入理解，合理设计和
选择联合治疗方案将成为未来克服ICI耐药的关键方向。
3 ccRCC中ICIs的临床研究及治疗策略演变
ICIs已引发晚期肾细胞癌（aRCC）治疗格局的根本性范式转变，尤其强调透明细胞组织学亚型（ccRCC）。目前，基于ICI的协同联合方案已成为一线干预的既定基石。除转移性疾病外，将ICIs战略性整合到围手术期为优化局限性RCC的临床结局开辟了新途径。这一演变基于连续临床研究的坚实证据基础，从单药治疗突破过渡到复杂的联合策略（图2）。评估这些方案的关键临床试验的综合总结见表1–4。
里程碑式的CheckMate 025试验确立了nivolumab单药在二线治疗中的疗效，推动了免疫检查点抑制剂（ICIs）在初治人群中的探索（18）。因此，晚期/转移性ccRCC（a/mccRCC）的治疗范式已明确从TKI单药治疗转变为基于ICI的联合方案。当前国际指南现推荐ICI-ICI或ICI-酪氨酸激酶抑制剂（TKI）联合方案作为首选标准治疗，因其在延长无进展生存期（PFS）和
总生存期（OS）方面以及稳健的客观缓解率（ORR）方面均优于既往基准药物舒尼替尼（103）。这一范式转变不仅反映了免疫治疗策略的临床成熟度，也重新定义了晚期肾恶性肿瘤患者的长期生存预期。
3.1 ICI–ICI联合治疗
CheckMate 214研究确立了nivolumab联合ipilimumab作为国际转移性RCC数据库联盟（IMDC）标准定义的中危和高危a/mccRCC患者的一线治疗地位（104）。Motzer R.J.等人报告的长期随访数据显示，该联合方案在中危/高危人群中具有持久的OS获益，中位OS为47.0个月，而舒尼替尼组为26.6个月（HR 0.69），完全缓解（CR）率约为11%（17, 104, 105）。值得注意的是，Tannir N.M.等人报告的近8年随访数据显示，即使在IMDC低危患者中，nivolumab联合ipilimumab的总生存期也优于舒尼替尼，而早期分析未显示明显优势，且PFS数据有利于舒尼替尼（104, 106）。
3.2 ICI-TKI联合治疗
ICIs与VEGFR-TKIs的联合代表了另一种成功的一线治疗策略，目前已有多项ICI-TKI方案获批。
帕博利珠单抗联合阿昔替尼（KEYNOTE-426研究）：Rini B.I.等人报告的KEYNOTE-426研究证实了
FIGURE 2 Overview of the major themes covered in this review of ICIs in ccRCC. This schematic summarizes (1) pivotal phase III clinical trials of ICI-based regimens in ccRCC, grouped by combination strategy; (2) key multi-omics advances linked to ICI response and resistance, including genomic/epigenomic features, tumor microenvironment heterogeneity, metabolic and proteomic programs, circulating biomarkers, and immune clonality/tertiary lymphoid structures; and (3) representative AI-enabled workflows integrating pathology images, radiology, and multi-omics data to support response prediction, biomarker discovery, and drug discovery.
TABLE 1 Summary of key phase III clinical trials of first-line ICI combination therapy for metastatic renal cell carcinoma.
(Continued)
TABLE 1 ContinuedAbbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BID, twice daily; ccRCC, clear cell renal cell carcinoma; CI, confidence interval; CR, complete response; DOR, duration of response; F, favorable-risk; HR, hazard ratio; I, intermediate-risk; ICI, immune checkpoint inhibitor; IMDC, International Metastatic Renal Cell Carcinoma Database Consortium; ITT, intent-to-treat; I/P, intermediate/poor-risk; TRAEs, treatment-related adverse events; NCT, National Clinical Trial (clinicaltrials.gov registration number); NR, not reached; OS, overall survival; P, poor-risk; PD, progressive disease; PD-L1, programmed death-ligand 1; PFS, progression-free survival; QD, once daily; Q2W, every 2 weeks; Q3W, every 3 weeks; RCC, renal cell carcinoma; SOC, standard of care; TKI, tyrosine kinase inhibitor.*COSMIC-313 demonstrated a progression-free survival benefit but no overall survival advantage versus nivolumab plus ipilimumab, with a higher rate of grade ≥ 3 treatment-related adverse events; accordingly, this triplet has not been widely adopted as standard of care. †Final long-term follow-up further showed that overall survival favored nivolumab plus ipilimumab over sunitinib in the IMDC favorable-risk subgroup, refining earlier analyses in which a clear advantage had not yet been observed.
TABLE 2 Summary of key clinical trials of second-line and subsequent ICI-related therapies for metastatic renal cell carcinoma.Abbreviations same as Table 1. AEs, adverse events; N/A, not applicable.
TABLE 3 Summary of key phase III clinical trials of adjuvant/neoadjuvant ICI therapy for renal cell carcinoma.Abbreviations same as Table 1 & 2. EFS, event-free survival; Pbo, placebo; N+I, Nivolumab+Ipilimumab.
TABLE 4 Clinical trial progress of emerging targets and drugs in RCC ICI therapy.Abbreviations as in previous tables. IO, immuno-oncology; SOC, standard of care.
帕博利珠单抗联合阿昔替尼在初治a/mccRCC患者中相比舒尼替尼具有显著的生存获益（107, 108）。根据Rini B.I.等人发表的近5年随访数据，联合组的中位OS为47.2个月，而舒尼替尼组为40.8个月（HR 0.79）；5年OS率分别为41.7%和37.3%；中位PFS为15.7
个月 vs 11.1个月（HR 0.69）（66, 104, 109–112）。东亚人群亚组分析（中位随访42.8个月）也显示了一致的疗效趋势，尽管OS HR的置信区间较宽（113）。
纳武利尤单抗联合卡博替尼（CheckMate 9ER研究）：CheckMate 9ER研究的结果证实了
纳武利尤单抗联合卡博替尼在aRCC一线治疗中优于舒尼替尼（114–116）。其3年随访数据显示，联合组的中位OS为49.5个月，而舒尼替尼组为35.5个月（HR 0.70）；中位PFS为16.6个月 vs 8.4个月（HR 0.58），ORR为55.7%，CR率为12.4%（114–116）。
帕博利珠单抗联合仑伐替尼（CLEAR/KEYNOTE-581研究）：Motzer R.J.等人报告的CLEAR研究表明，帕博利珠单抗联合仑伐替尼一线治疗aRCC患者相比舒尼替尼在PFS、OS和ORR方面均有显著改善（117, 118）。该联合方案实现了23.9个月的中位PFS、71.3%的ORR和18.3%的CR率，使其成为迄今为止报道的反应深度和PFS最令人印象深刻的ICI-TKI方案之一（117–119）。尽管最终分析显示联合组和舒尼替尼组的中位OS数值相似（53.7 vs 54.3个月），但HR为0.86证实了联合方案的持续生存获益，捕捉到了超越单一时间点中位估计值的整体死亡风险降低。在该研究的最终预设OS分析中（中位随访50.1个月），帕博利珠单抗联合仑伐替尼组的中位OS为53.7个月，而舒尼替尼组为54.3个月（HR 0.86）（117–119）。
跨试验比较的局限性。一线ccRCC试验中ORR、PFS和OS的明显差异不应被解释为比较优越性的证据。跨试验比较受到入选标准异质性、IMDC风险分布、基线疾病负荷（包括肉瘤样特征）、PD-L1检测方法和临界值、终点定义和评估时间表、随访持续时间以及后续治疗可及性的混杂影响。因此，方案排序需要头对头研究或适当调整的比较分析，而非无锚定的数值比较。
3.3 IMDC风险分层
IMDC风险模型是指导晚期RCC一线治疗决策的关键工具（104, 120）。对于低危患者，当前指南推荐ICI-TKI联合方案作为标准治疗（104, 120）。尽管CheckMate 214的长期随访显示在低危组中OS有利于纳武利尤单抗联合伊匹木单抗，但由于其在该亚组中更高的缓解率和更有利的PFS结果，ICI-TKI联合方案在此背景下仍更常被选择（17, 104, 105）。对于中危或高危患者，纳武利尤单抗联合伊匹木单抗和各种ICI-TKI联合方案均被NCCN和ESMO等权威指南推荐为一线选择（121, 122）。目前，由于其通常更高的ORR和更长的中位PFS，ICI-TKI方案在大多数情况下已成为更广泛适用的一线选择（117–119）。然而，纳武利尤单抗联合伊匹木单抗仍发挥重要作用，在部分患者中可产生深度且持久的缓解，长期随访也显示在选定的低危患者中具有OS获益（104, 121, 122）。
3.4 三联疗法
为进一步提高疗效，研究者已探索三联疗法。Choueiri T.K.等人报告的COSMIC-313研究评估了在纳武利尤单抗联合伊匹木单抗基础上加用卡博替尼（cabo+nivo+ipi）作为IMDC中危或高危aRCC患者的一线治疗（123）。研究数据显示，三联疗法相比安慰剂加nivo+ipi显著改善了PFS（中位未达到 vs 11.3个月；HR 0.73）。然而，根据更长随访时间的已发表数据，OS无显著差异，且三联组3/4级治疗相关不良事件（TRAEs）发生率更高（81% vs 62%），这对其未来的临床应用提出了挑战（123）。
3.5 RCC的围手术期ICI治疗
辅助治疗旨在降低高危局限性RCC患者术后复发风险。KEYNOTE-564研究的突破性结果代表了该领域的里程碑。Choueiri T.K.和Powles T.等人的研究显示，在中位随访57.2个月时，辅助帕博利珠单抗相比安慰剂显著改善了DFS（HR 0.72）和OS（HR 0.62），确立了其在该人群中的标准治疗地位（101, 124, 125）。相比之下，其他辅助治疗试验，如IMmotion010（atezolizumab）、CheckMate 914（nivolumab +/- ipilimumab）和PROSPER RCC（围手术期nivolumab），均未能达到其主要终点（126–129）。
新辅助ICI治疗的理论优势在于利用原位肿瘤引发更强的免疫反应（84, 130）。迄今为止已发表的数据主要来自小型I/II期临床试验，显示新辅助ICI单药治疗通常产生较低的ORR和罕见的病理完全缓解（pCRs）（84, 130）。除基于ICI的方法外，VEGF-TKI卡博替尼也作为局部晚期非转移性ccRCC的靶向新辅助选择显示出临床活性和安全性（131）。
然而，优化围手术期治疗策略是一个复杂问题，新辅助治疗面临手术延迟和如何最佳评估病理反应等挑战（132）。
4 多组学技术揭示肾细胞癌免疫治疗机制的新维度
多组学技术的应用为系统理解ccRCC治疗反应异质性和ICI耐药机制提供了关键数据和新视角，推动该领域从现象观察走向机制驱动的个体化治疗探索（30）（图2）。
基因组和表观基因组改变构成了影响RCC对ICI治疗反应的基础。肿瘤基因组测序
分析揭示了特定突变与ICI疗效的关联。例如，Deutsch等人的研究表明，将肿瘤组织学特征与PBRM1等基因的突变状态整合可构建更有效的ICI疗效预测模型（133）。此外，Hagiwara等人的研究表明，在PBRM1突变型ccRCC中，DNA损伤修复（DDR）通路基因（如PARP1）的低表达可能预测PD-L1抑制剂更好的总生存期（134）。为提供平衡的分子概览，BAP1突变定义了ccRCC中一种独特且侵袭性强的增殖亚型，并被报道与PBRM1基本互斥，支持不同的分子轨迹（135）。一致地，IMmotion151的整合多组学分析表明，增殖性转录程序可能与VEGF靶向治疗和基于ICI的联合方案的不同结局相关，强调需在更广泛的分子背景下解读单基因标志物（66）。在表观基因组层面，Yu和Lu等人通过ATAC-seq等技术生成的染色质可及性图谱有助于识别调控ccRCC关键生物学行为（如侵袭和迁移）的非编码RNA（lncRNAs）和顺式调控元件，为理解基因表达调控的表观遗传机制提供基础（136, 137）。
转录组学分析，特别是单细胞RNA测序（scRNA-seq）、空间转录组学和免疫组库测序的整合应用，极大地加深了我们对RCC TME内细胞异质性、免疫动态和空间组织的理解。这为阐明ICI作用机制和发现新生物标志物提供了核心见解。TME细胞组成、功能状态及其空间分布对ICI疗效的决定性作用是当前研究热点。scRNA-seq技术已成功鉴定出RCC TME内的多个新或关键细胞亚群。例如，Ge等人的研究发现，在ICB耐药的ccRCC中显著富集了一种具有M2样免疫抑制表型的APOE阳性巨噬细胞群体；这些细胞的比例与不良预后和较差的ICB疗效密切相关。肿瘤细胞分泌的SPP1被发现可招募并极化这些巨噬细胞，后者通过释放TGF-β抑制T细胞功能。同时，这些巨噬细胞中CEBPD的高表达也与免疫抑制相关（138）。Krishna等人利用多区域scRNA-seq分析揭示了组织驻留记忆T细胞（Trm）和特定TAM亚群的基因表达特征与肿瘤拓扑结构和ICI反应性的强关联（139）。同时，Davidson等人的研究表明，ccRCC中的间质样肿瘤细胞和肌成纤维细胞样癌相关成纤维细胞（myoCAFs）凭借其独特的基因表达谱和交互信号，与疾病进展和免疫治疗反应密切相关，共同凸显了肿瘤和基质细胞异质性对ICI疗效的关键影响（81）。Bi等人的奠基性工作系统绘制了晚期RCC患者免疫治疗期间TME内肿瘤细胞和各种免疫细胞的动态重编程图谱，为理解ICI作用机制和耐药提供了早期单细胞视角（140）。这些研究共同强调了scRNA-seq在识别TME内关键细胞参与者及其相互作用网络中的关键作用，特别是在揭示巨噬细胞异质性和肿瘤-基质相互作用对ICI耐药机制的核心贡献方面。
空间转录组学进一步实现了对这些细胞状态的原位研究。Raghubar等人发现，高级别ccRCC的TME富含具有耗竭或促肿瘤表型的免疫细胞，但这些细胞并不一致地过表达经典免疫检查点基因。此外，特定类型的单核细胞被发现空间包绕耗竭的CD8 + T细胞并高表达TIM-3和LAG-3（141）。Kinget等人通过整合空间多组学数据，在ICB应答的晚期RCC患者中鉴定了促炎性TAMs和耗竭CD8+ T细胞之间的特定空间互作模式。这与有利HLA等位基因的表达相关，基于此构建的HLA相关基因表达特征可有效预测ICB疗效（142）。这些发现凸显了TME细胞空间排列对ICI效果的关键影响。
适应性免疫反应的克隆演化和三级淋巴结构（TLS）等有序结构在ICI疗效中的作用日益受到关注。Au等人的ADAPTeR研究中的免疫组库测序揭示，mRCC患者对nivolumab的反应与治疗前预扩增TCR克隆的数量及治疗后这些克隆簇的持续维持显著相关，强调了“预先存在的免疫力”的重要性（39）。Meylan等人的空间分析研究发现，RCC肿瘤内的TLS是原位B细胞成熟和抗体产生的关键部位，且IgG包被的肿瘤细胞与更好的ICI治疗反应和更长的PFS相关（83）。后续研究进一步证实，高密度、成熟的TLS与ccRCC患者的有利预后和治疗反应性相关，且TLS在肿瘤内的空间位置和成熟状态对其功能至关重要（143, 144）。这些发现表明，B细胞介导的体液免疫和TLS可能在抗肿瘤免疫中发挥先前被低估的关键作用。结合先进算法的批量RNA测序继续为发现与ICI治疗反应相关的分子机制和基因表达谱提供重要信息。通过分析多项ICI临床试验的批量RNA测序数据，Tian等人发现，肿瘤细胞中高水平的氧化磷酸化（OXPHOS）特征是RCC患者ICI治疗结局不佳的风险因素，其机制可能通过影响TME缺氧和T细胞功能介导（68）。
蛋白质组学和代谢组学为RCC对ICI治疗反应的功能输出提供了直接证据，现有研究已鉴定出几种与ICI疗效相关的循环代谢物或通路改变。例如，Li等人的研究表明，在ICI治疗期间血液中犬尿氨酸/色氨酸（Kyn/Trp）比率升高与患者较差的生存预后相关（145）。结合
Tian等人从转录组水平关于OXPHOS通路在ICI耐药中作用的上述发现（68），这指向“代谢检查点”是介导ICI耐药的关键因素。这些发现表明，循环代谢物具有作为动态、无创生物标志物的潜力。同样，在蛋白质组学领域，循环血浆中蛋白质的分析正成为探索ICI治疗反应生物标志物的重要方向。例如，Montemagno C.等人的研究发现，mRCC患者血浆中可溶性PD-1（sPD-1）和PD-L1（sPD-L1）的水平可能与不同治疗方案的疗效相关（146）。Maritaz等人观察到，较高浓度的IL-8和LDH与总生存期相关（19）；Schoenfeld等人提出，循环IL-18BP水平及其变化可作为ICI疗效的潜在预测生物标志物（10）；Pourmir等人发现可溶性TIM-3可预测耐药（93）。此外，对细胞外囊泡（如外泌体）中蛋白质成分的液体活检分析（例如，尿液外泌体中的CA9、CP、MMP9、DKK4、PODXL等蛋白质）也正在探索其作为诊断和预测ICI反应的无创生物标志物的潜在应用（147）。
这些基于多组学层面的深入研究为RCC ICI治疗的反应和耐药机制提供了关键见解，推动了该疾病精准免疫治疗策略的发展。
5 AI驱动的肾细胞癌ICI免疫治疗
人工智能（AI），特别是机器学习（ML）和深度学习（DL）算法，因其在处理高维复杂数据、识别细微模式和构建预测模型方面的卓越能力，正成为推动RCC ICI治疗进入个性化精准医学时代的关键技术（148, 149）。传统生物标志物如PD-L1表达和肿瘤突变负荷（TMB）在预测RCC ICI疗效方面显示出有限效用，未能满足临床对准确预测工具的迫切需求（150, 151）。通过整合包括放射组学、病理组学、基因组学和临床数据在内的多维信息，AI有望在新生物标志物发现、治疗疗效和预后预测及管理等多个领域实现突破（图2）。
肾损伤分子-1（KIM-1）已成为ccRCC中特别有前景的循环生物标志物，尽管其当前临床应用主要通过相对简单的分层方法进行探索。III期IMmotion010辅助试验的生物标志物分析显示，肾切除术后较高的血浆KIM-1与复发风险增加相关，且KIM-1动力学纵向追踪疾病复发；值得注意的是，辅助atezolizumab与安慰剂的治疗效应估计值在KIM-1定义的亚组间存在差异，支持KIM-1作为微小残留病和潜在治疗选择的候选标志物（152）。将系列KIM-1测量值与放射组学、病理组学、多组学和临床变量整合，可能为AI驱动的风险分层提供更合适的环境，特别是在需要建模非线性交互、纵向变化和多变量模式而超越简单二分临界值的情况下。
数字病理学，尤其是与全切片成像（WSI）的AI算法结合，催生了新兴的病理组学领域，旨在从WSI中高通量提取和分析大量可量化的形态学和空间特征（153–155）。研究表明，AI在RCC的诊断、组织学亚型分类和分级方面表现卓越。例如，基于手工特征的ML模型可区分不同级别的透明细胞RCC（ccRCC）（156, 157）。此外，基于深度神经网络的模型可准确区分各种RCC亚型并对ccRCC进行ISUP核分级（156–158）。除基本诊断和分级外，AI模型已被用于直接从苏木精-伊红（H&E）染色的病理图像预测ccRCC患者的预后和生存（156, 157）。Wessels等人表明，DL模型可直接从H&E图像预测总生存期（OS），在多变量分析中显示出显著预测价值（159）。重要的是，病理组学在预测ICI治疗反应方面也显示出前景。AI驱动的空间分析工具可分割和量化肿瘤浸润淋巴细胞（TILs），并根据TILs的空间分布将TME分类为不同的免疫表型（如炎症型、免疫排除型和免疫沙漠型）；这些表型与ICI治疗后的客观缓解率（ORR）和无进展生存期（PFS）显著相关（32）。尽管这些研究主要集中在非小细胞肺癌（NSCLC），但类似的AI驱动空间分析方法同样适用于RCC，以评估TME的免疫细胞组成和空间架构，这对预测ICI反应至关重要（160）。此外，Park等人开发的Lunit SCOPE IO深度学习模型可自动分析H&E染色的WSI，按免疫表型（例如，炎症免疫表型，IIP）对肿瘤进行分类（32）。病理组学的另一项重要进展是利用AI从组织学图像预测肿瘤的分子特征，如基因突变状态。在其他癌症类型中，AI已成功预测多种基因突变（结直肠癌中的BRAF、KRAS、NRAS和PIK3CA，肺癌中的ALK、ROS1和TP53）（161, 162）。开发类似AI模型从ccRCC的H&E图像预测特定ICI驱动基因突变（如PBRM1、BAP1和SETD2）在技术上可行且生物学上合理。此类预测模型的开发将促进在组织学水平获取肿瘤分子异质性信息，进一步优化ICI治疗的患者选择。
放射组学涉及使用先进算法从标准医学图像（如CT、MRI和PET）中高通量提取大量定量特征。这些特征随后用于构建数学模型，以无创方式揭示肿瘤生物学、预测治疗反应和确定患者预后（163–165）。在RCC ICI治疗背景下，放射组学作为预测疗效和表征肿瘤的无创工具的潜力日益明显。近年来，几项研究探索了
使用治疗前CT或超声图像的放射组学特征预测RCC患者对ICI治疗的反应。例如，Khene等人研究了放射组学在预测转移性RCC（mRCC）患者对nivolumab治疗反应中的潜力（166）。此外，Rossi E等人分析了接受ICI治疗的晚期RCC患者的基线CT图像，发现几种一阶统计放射组学特征与疾病进展显著相关，提示基线CT图像的定量特征可用于早期识别对ICI反应不佳的患者（167）。Duwe G等人利用全自动AI分割技术评估脾脏体积变化，发现治疗开始后早期较小的脾脏体积与晚期RCC患者改善的OS相关，从而为监测ICI疗效提供了新视角（168）。这些研究表明，放射组学可捕捉人眼无法察觉的肿瘤异质性信息，这可能间接反映与ICI疗效相关的肿瘤内部生物学特性。然而，放射组学研究的临床转化仍面临挑战，包括图像采集标准化、特征提取稳健性、模型可重复性和多中心外部验证。未来研究需要更严格地遵循标准化协议，并在大规模前瞻性队列中验证这些模型的临床效用（169, 170）。
整合计算和实验策略的多方面方法正在加速新型免疫治疗药物的发现。AI与高通量筛选的结合能够分析庞大的化学和生物数据集，从而高效识别具有潜在免疫调节特性的化合物（171, 172）。先进的筛选平台，如模拟癌症免疫微环境或利用共培养系统的平台，可同时测试大量化合物以发现增强抗肿瘤免疫反应的小分子免疫调节剂（173–176）。例如，高通量免疫调节表型筛选平台（HTiP）已成功鉴定出凋亡蛋白抑制剂（IAPs）作为潜在的抗癌免疫增强剂（173, 174）。作为这些方法的补充，“药物再利用”策略通过筛选已批准药物库以寻找先前未被识别的免疫调节作用，提供了一种省时且经济高效的方法；阿德福韦酯对T细胞增殖的抑制作用的发现就是一例（177）。此外，机器学习算法可利用公共生物活性数据预测药物-靶点相互作用并生成假设，从而优化候选药物的优先级以供进一步研究（178, 179）。
除药物发现外，AI在基于个体患者特征个性化免疫治疗以最大化疗效方面发挥着关键作用。AI算法可分析复杂的基因组和转录组数据集以指导精准治疗，例如预测患者最有效的ICI治疗方案（180–182）。这种免疫基因组学方法的核心是利用AI驱动技术识别肿瘤特异性新抗原，这对于开发可利用患者独特免疫反应的个性化疫苗和靶向治疗至关重要（183–187）。为更全面地表征肿瘤并更准确地预测ICI疗效，整合分析多组学数据——包括
基因组学、转录组学和蛋白质组学——正成为一种强大策略。AI，特别是深度学习算法，在处理和整合此类高维异质数据方面具有天然优势。例如，COMPASS模型利用Transformer和“概念瓶颈”设计，通过将肿瘤转录组映射到一层生物学可解释的免疫概念来预测ICI治疗反应（188）。同样，对ccRCC患者的多组学整合分析鉴定了三种具有不同分子特征、临床预后和对不同治疗（包括PD-1抑制剂）敏感性的分子亚型（189）。其他先进模型，如基于Transformer的MutFormer工具，可用于预测错义突变的致病性，从而加深我们对用于治疗靶向的肿瘤遗传景观的理解（190）。尽管多组学整合和大模型仍面临数据获取、异质性处理和模型可解释性等挑战，但它们无疑为实现个体化精准ICI治疗铺平了道路（191–193）。
总结
本研究是一篇系统性综述，旨在全面梳理和阐释透明细胞肾细胞癌（ccRCC）中免疫检查点阻断（ICI）疗效与耐药性的多层次机制，重点整合了肿瘤内在驱动因素、免疫抑制性肿瘤微环境（TME）的复杂构成、多组学技术（单细胞/空间转录组、表观基因组、蛋白组、代谢组）的深度解析能力，以及人工智能（AI）在病理图像、医学影像和多组学数据整合分析中的前沿应用，为推进ccRCC的精准免疫治疗提供了全面的理论框架与实践路径。
更多结果和补充图表:
PMID：42206054
DOI：10.3389/fimmu.2026.1774959
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| 适应症 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|
| 晚期子宫内膜癌 | 欧盟 | 2023-07-25 | |
| 晚期子宫内膜癌 | 冰岛 | 2023-07-25 | |
| 晚期子宫内膜癌 | 列支敦士登 | 2023-07-25 | |
| 晚期子宫内膜癌 | 挪威 | 2023-07-25 | |
| 复发性子宫内膜癌 | 欧盟 | 2023-07-25 | |
| 复发性子宫内膜癌 | 冰岛 | 2023-07-25 | |
| 复发性子宫内膜癌 | 列支敦士登 | 2023-07-25 | |
| 复发性子宫内膜癌 | 挪威 | 2023-07-25 | |
| 胸腺肿瘤 | 日本 | 2021-03-23 | |
| 晚期肾细胞癌 | 欧盟 | 2016-08-25 | |
| 晚期肾细胞癌 | 冰岛 | 2016-08-25 | |
| 晚期肾细胞癌 | 列支敦士登 | 2016-08-25 | |
| 晚期肾细胞癌 | 挪威 | 2016-08-25 | |
| 子宫内膜癌 | 澳大利亚 | 2016-01-28 | |
| 肾细胞癌 | 澳大利亚 | 2016-01-28 | |
| 晚期肝细胞癌 | 欧盟 | 2015-05-28 | |
| 晚期肝细胞癌 | 冰岛 | 2015-05-28 | |
| 晚期肝细胞癌 | 列支敦士登 | 2015-05-28 | |
| 晚期肝细胞癌 | 挪威 | 2015-05-28 | |
| 分化型甲状腺癌 | 欧盟 | 2015-05-28 |
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10 条进展最快的记录, 后查看更多信息
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 晚期非小细胞肺癌 | 临床3期 | 中国 | 2021-10-28 | |
| 转移性食管癌 | 临床3期 | 美国 | 2021-07-28 | |
| 转移性食管癌 | 临床3期 | 美国 | 2021-07-28 | |
| 转移性食管癌 | 临床3期 | 中国 | 2021-07-28 | |
| 转移性食管癌 | 临床3期 | 中国 | 2021-07-28 | |
| 转移性食管癌 | 临床3期 | 日本 | 2021-07-28 | |
| 转移性食管癌 | 临床3期 | 日本 | 2021-07-28 | |
| 转移性食管癌 | 临床3期 | 阿根廷 | 2021-07-28 | |
| 转移性食管癌 | 临床3期 | 阿根廷 | 2021-07-28 | |
| 转移性食管癌 | 临床3期 | 加拿大 | 2021-07-28 |
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临床结果
临床结果
适应症
分期
评价
查看全部结果
| 研究 | 分期 | 人群特征 | 评价人数 | 分组 | 结果 | 评价 | 发布日期 |
|---|
临床3期 | 复发性子宫内膜癌 辅助 | 新辅助 | 421 | Lenvatinib 20 mg once daily+pembrolizumab 200 mg every 3 weeks | 衊範範選築鹽顧鹹築夢(簾廠鬱構膚廠艱構窪廠) = 網觸憲壓鏇夢膚遞膚餘 夢鹹壓蓋淵膚蓋築構網 (範壓觸醖簾構餘窪衊夢, 14.0 ~ 22.8) 更多 | 积极 | 2026-07-01 | |
Chemotherapy (doxorubicin or paclitaxel) | 衊範範選築鹽顧鹹築夢(簾廠鬱構膚廠艱構窪廠) = 餘簾壓鹽淵顧顧鏇觸膚 夢鹹壓蓋淵膚蓋築構網 (範壓觸醖簾構餘窪衊夢, 10.9 ~ 15.5) 更多 | ||||||
临床2期 | 3 | 艱選餘製淵壓簾壓醖醖 = 繭簾蓋衊廠廠鹽糧積簾 鹹鹽網製觸鏇醖簾鬱築 (夢製壓膚蓋網廠觸襯鹹, 鬱鹹繭齋構鑰簾糧蓋憲 ~ 鑰範築夢繭積鑰築觸襯) 更多 | - | 2026-06-23 | |||
临床2期 | 116 | 願選積觸積網鹹顧餘膚 = 糧窪餘餘繭獵齋膚繭願 選簾衊繭積糧艱衊夢齋 (淵製鬱獵積鏇獵壓糧願, 遞衊顧醖蓋築構壓餘糧 ~ 憲鹽製獵夢艱憲獵齋廠) 更多 | - | 2026-06-23 | |||
临床2期 | 18 | (Cohort 1: Melanoma) | 構醖餘簾淵鏇鹽鬱願膚 = 鬱鹹構餘簾願膚淵願選 鏇餘鑰鹽積鑰鹽餘網壓 (遞襯廠顧壓鏇鏇鹹蓋艱, 夢蓋選顧艱鏇醖鬱窪壓 ~ 窪淵夢獵襯製鑰顧網艱) 更多 | - | 2026-06-04 | ||
(Cohort 2: Renal Cell Carcinoma) | 構醖餘簾淵鏇鹽鬱願膚 = 選製夢顧網廠選鏇壓醖 鏇餘鑰鹽積鑰鹽餘網壓 (遞襯廠顧壓鏇鏇鹹蓋艱, 選選積壓餘鹹艱鏇觸淵 ~ 艱衊蓋觸鑰範築餘鹹網) 更多 | ||||||
临床2期 | 135 | 顧壓廠壓糧餘選醖網構(網獵鬱餘積構窪鏇衊淵) = 獵艱夢築餘願襯願餘艱 繭構廠窪蓋糧廠選壓製 (廠淵網鬱鹽顧艱範襯網, 8 ~ 23) 更多 | 积极 | 2026-06-01 | |||
顧壓廠壓糧餘選醖網構(網獵鬱餘積構窪鏇衊淵) = 餘觸鹹窪醖築淵襯願襯 繭構廠窪蓋糧廠選壓製 (廠淵網鬱鹽顧艱範襯網, 1 ~ 22) 更多 | |||||||
临床2期 | 30 | 願鏇淵鏇鏇襯鑰網簾願(製鹽襯壓糧鑰築鹹糧範) = 鬱鑰選壓遞糧夢鹹艱夢 選餘鬱觸獵遞構製餘積 (鏇積壓襯壓鹹選製願繭, 8.3 ~ 20.7) 更多 | 积极 | 2026-05-29 | |||
N/A | 142 | 夢觸衊製艱獵網窪齋淵(夢選憲構築糧鹽壓鹽鏇) = 獵衊糧鏇鹹壓窪構遞壓 築廠製糧醖壓艱簾鹽糧 (糧艱範鬱築蓋襯鏇鏇鑰, 51.8 ~ 90.8) 更多 | 积极 | 2026-05-29 | |||
夢觸衊製艱獵網窪齋淵(夢選憲構築糧鹽壓鹽鏇) = 觸遞構衊憲廠膚襯顧廠 築廠製糧醖壓艱簾鹽糧 (糧艱範鬱築蓋襯鏇鏇鑰, 16.4 ~ 66.4) 更多 | |||||||
临床2期 | 肝细胞癌 一线 | 40 | 網觸構壓鑰糧艱襯衊獵(願餘顧淵餘鏇鑰餘鑰夢) = 鹹廠廠選構憲餘選鬱衊 獵選襯構窪淵鬱鹹醖壓 (衊築蓋艱鬱繭壓顧淵窪 ) 更多 | 积极 | 2026-05-29 | ||
临床3期 | 668 | 積餘選範遞範鹽餘餘遞(繭齋範窪夢繭廠衊獵糧) = 蓋選獵鹹糧廠鏇壓鏇衊 壓網製糧築淵廠積遞網 (構齋餘製築觸選衊築衊 ) | 积极 | 2026-05-29 | |||
临床2期 | 肝细胞癌 一线 | 244 | 襯蓋淵糧觸襯廠襯選積(構膚簾積獵積製醖鹹壓) = 製願遞觸鹽鹽淵願齋鹽 網簾積醖選網襯觸觸獵 (鏇選壓鹹積獵選簾鹹繭, 22.0 ~ 33.7) 更多 | 积极 | 2026-05-29 | ||
Lenvatinib + PD-1 inhibitors | 襯蓋淵糧觸襯廠襯選積(構膚簾積獵積製醖鹹壓) = 窪鬱網膚淵餘壓獵壓築 網簾積醖選網襯觸觸獵 (鏇選壓鹹積獵選簾鹹繭, 12.6 ~ 21.3) 更多 |
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