REal-World Application of Luspatercept in Adults With Transfusion-Dependent Beta-Thalassemia in the Middle East (RELATE): A Non-interventional Retrospective and Prospective Observational Study

The purpose of this study is to evaluate luspatercept treatment in adults with transfusion-dependent beta-Thalassemia in the Middle East

开始日期2026-06-25

申办/合作机构

Bristol Myers Squibb Co.

NCT07463820

/ Not yet recruiting临床2期IIT

A Phase II Study of Combination Therapy With Luspatercept in Lower Risk Myelodysplasia: A Tier 1 MyeloMATCH Substudy

This phase II MyeloMATCH treatment trial tests luspatercep with or without epoetin alfa or emavusertib for the treatment of low risk myelodysplasia and anemia. Biological therapies, such as luspatercep, use substances made from living organisms that may attack specific cancer cells and stop them from growing or kill them. Epoetin alfa is a substance that is made in the laboratory and stimulates the bone marrow to make red blood cells. Emavusertib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving luspatercep with or without epoetin alfa or emavusertib may be effective for treating patients with low risk myelodysplasia and anemia.

开始日期2026-06-19

申办/合作机构

National Cancer Institute

NCT07636486

/ Not yet recruiting临床2/3期IIT

Luspatercept Versus Epoetin in Treating Poor Erythroid Engraftment for Hematological Malignancies

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective therapy for hematological malignancies. Nonetheless, poor graft function remains a life-threatening complication after allo-HSCT. Poor erythroid engraftment is associated with increased bleeding events and shorter survival. Current treatment methods such as epoetin or repeated red-cell transfusions are not effective for poor erythroid engraftment, with limited and transient responses. Retrospective studies suggested that luspatercept showed efficacy in patients with anemia post-transplantation or poor erythroid engraftment. However, there are no studies comparing luspatercept versus epoetin for the treatment of poor erythroid engraftment. Therefore, we conducted a randomized controlled study to compared the effect of luspatercept versus epoetin in treating poor erythroid engraftment for hematological malignancies.

开始日期2026-06-15

申办/合作机构

南方医科大学南方医院

100 项与罗特西普相关的临床结果

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100 项与罗特西普相关的转化医学

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100 项与罗特西普相关的专利（医药）

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280

项与罗特西普相关的文献（医药）

2026-09-01·CLINICA CHIMICA ACTA

Erythroferrone in β-thalassemia: Systematic review and meta-analysis

Review

作者: Saboor, Muhammad ; Abass, Khaled

Erythroferrone suppresses hepcidin and has emerged as a candidate biomarker of ineffective erythropoiesis in β-thalassemia. No prior meta-analysis has quantitatively synthesised circulating ERFE data. A PRISMA 2020-compliant systematic review and meta-analysis (PROSPERO: CRD420261347288) searched PubMed/MEDLINE, Scopus, and Web of Science up to March 2026. Hedges' g was pooled using random-effects REML; correlation outcomes were Fisher z-transformed. Seven pre-specified sensitivity analyses evaluated robustness. Thirteen studies (975 patients; 350 controls; 2019-2026) were included. Six met primary meta-analysis criteria (k = 6; n = 541), yielding a large pooled effect (g = 2.700; 95%CI: 0.906-4.495; p = 0.003; I² = 96.1%), with all seven sensitivity analyses remaining significant (g range: 1.882-3.028). The ERFE-hepcidin pool demonstrated a significant inverse association with zero heterogeneity (r = -0.342; 95%CI: -0.472, -0.197; p < 0.001; I² = 0.0%). A significant positive ERFE-ferritin correlation was identified (r = +0.439; p = 0.0002); ERFE-hemoglobin was non-significant (r = -0.205; 95%CI: -0.515, +0.153; p = 0.260). Four studies reported formal ROC analyses yielding a weighted pooled AUC of 0.872 (range: 0.766-0.940). One study documented a 51% ERFE increase following luspatercept (p < 0.0001). ERFE is markedly elevated in β-thalassemia and inversely correlates with hepcidin in a homogeneous and reproducible manner. Assay standardisation and prospective validation are required before clinical implementation.

2026-07-01·EUROPEAN JOURNAL OF HAEMATOLOGY

Patient‐Reported Outcomes With Luspatercept Through 5 Years of Treatment in Patients With Non‐Transfusion‐Dependent β‐Thalassemia Treated in the BEYOND Trial

Article

作者: Kuo, Kevin H. M. ; Musallam, Khaled M. ; Reverte, Marta ; Guo, Shien ; Hnoosh, Ahmed ; Dyer, Matthew ; Eliason, Laurie ; Pelligra, Christopher G. ; Medlin, Loyse Felber ; Mu, Yutian ; Kattamis, Antonis ; Taher, Ali T. ; Cappellini, Maria Domenica

ABSTRACT:

In the phase 2, double‐blind, randomized controlled BEYOND trial (NCT03342404), luspatercept increased hemoglobin levels in patients with non‐transfusion‐dependent β‐thalassemia (NTDT). This study assessed long‐term effects of luspatercept on patient‐reported outcomes (PROs), using data from BEYOND and patients who continued luspatercept treatment in the phase 3b long‐term follow‐up (LTFU) study (NCT04064060). In BEYOND, patients received luspatercept or placebo Q3W for ≥ 48 weeks. PRO instruments included NTDT‐PRO (BEYOND only), Functional Assessment of Chronic Illness Therapy—Fatigue (FACIT‐F), and 36‐Item Short Form Survey (SF‐36). Mixed‐effects models with repeated measures estimated least squares mean changes from baseline in PROs. PROs were evaluable in 144 patients (luspatercept 95, placebo 49) from BEYOND and 58 (luspatercept) from LTFU. Luspatercept improved NTDT‐PRO tiredness/weakness and shortness of breath domain, FACIT‐F fatigue subscale, and SF‐36 vitality scores versus placebo through double‐blind treatment (generally maintained through week 96). In LTFU patients, significant, meaningful improvements from baseline in FACIT‐F fatigue subscale and SF‐36 vitality scores were observed within 12 weeks of treatment initiation and maintained for up to 5 years. Other FACIT‐F and SF‐36 domains improved or were maintained throughout LTFU. Luspatercept offers rapid and durable benefits by improving anemia‐related symptoms and quality of life in patients with NTDT.Trial Registration:ClinicalTrials.gov Identifier: NCT03342404; NCT04064060

2026-06-07·Leukemia & Lymphoma

A phase I open label study of fostamatinib, a SYK inhibitor, in patients with lower-risk myelodysplastic syndrome and chronic myelomonocytic leukemia

Article

作者: Borthakur, G. ; Garcia-Manero, G. ; Hwang, H. ; Chien, K. ; Shneider, H. ; Huang, X. ; Romero, L. ; Bose, P. ; Pierce, S. ; DiNardo, C. ; Hatfield, M. ; Hammond, D. ; Croden, J. ; Short, N. ; Montalban-Bravo, G.

Lower-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) are commonly managed with erythropoiesis-stimulating agents, luspatercept, or hypomethylating agents. Despite this, the disease often becomes refractory and patients develop transfusion dependence. Preclinical evidence suggests that targeting innate immune signaling, including NF-kB activation, may improve hematopoiesis. Fostamatinib, an oral SYK inhibitor approved for immune thrombocytopenia, was evaluated in a phase 1 open-label study in previously treated lower-risk MDS/CMML. Eleven patients received fostamatinib starting at 100 mg twice daily with dose escalation for lack of response. Patients had received a median of 3 prior therapies and most were transfusion-dependent. Over a median of 5 treatment cycles and 14.4 months of follow-up, no objective responses were observed, although all patients achieved stable disease. Transfusion needs remained largely unchanged. There were no dose-limiting toxicities. Although safe, fostamatinib demonstrated no clinical benefit, underscoring the need for alternative strategies to modulate inflammatory signaling in MDS/CMML.

450

项与罗特西普相关的新闻（医药）

2026-07-23

·北京医学感染与传染研究

生物医学中心 - 医学 24卷 1期（上半年）

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

2026-07-20

·感悟分子

Halia Therapeutics 公司深度分析

「遗传韧性」（Genetic Resilience）平台公司 · NEK7 / NLRP3 炎症小体 + LRRK2 / RAB10 轴 · 报告日期 2026-07-20 私有临床阶段 Biotech 2017 成立 · Lehi, Utah The Genetic Resilience Company™ CEO David J. Bearss, PhD Halia Therapeutics 是一家以「人类遗传韧性」为底层逻辑的私有临床阶段生物制药公司，2017 年创立于犹他州 Lehi。其科学原点来自杨百翰大学 John “Keoni” Kauwe 教授的发现：一个携带高风险 APOE4 基因却终生未患阿尔茨海默病的大家族，体内存在一个 RAB10 保护性突变。Halia 据此搭建了「LRRK2（上游）→ RAB10 → NEK7（下游）→ NLRP3 炎症小体」的靶向轴，并由此衍生出两条临床主线——以 NEK7 别构调节剂 Ofirnoflast（HT-6184）主攻血液学与系统炎症，以脑渗透 LRRK2 抑制剂 HT-4253 主攻神经炎症/阿尔茨海默病预防。本报告从管线、机制、财务、竞争格局、催化剂与风险六个维度做结构化拆解。最新核心拐点（2026 年 6 月）：Ofirnoflast 在 EHA2026 以口头报告形式读出 lower-risk MDS（LR-MDS）II 期最终数据（多谱系血液学改善、持久脱离输血、安全性优异），并同步获得 FDA Fast Track 认定（2026-06-15）。这是 NEK7 路径首个进入后期临床、且取得阳性概念验证的口服药物，确立了 Halia 在「上游炎症小体」赛道的事实领先地位。一、公司身份与治理 Halia 总部位于犹他州 Lehi（3900 N Traverse Mountain Blvd），员工约 26–50 人（TipRanks 2026-06 口径约 26 人），属典型「轻资产、重发现」型临床阶段 Biotech。公司由 David J. Bearss, PhD 驱动——他是连续创业者，曾联合创立 8 家生物公司，累计推动 16 个化合物从发现走到 IND；此前任 Tolero Pharmaceuticals CEO（2017 年被 Sumitomo Dainippon 收购），更早任职 Montigen / SuperGen。他于 2021 年 1 月加入 Halia 任 CSO、2022 年 3 月转任 CEO，是公司的科学灵魂与资本引擎。 2026 年公司治理显著强化：Gary Sabin 于 2026 年 5 月出任执行董事长（Executive Chairman），Han Myint, MD, FACP 于 2026 年中加入任首席医学官（CMO）。Myint 拥有 30 余年恶性血液学与全球药物开发经验，曾任 Celgene 全球髓系疾病负责人、NextCure 与 NexImmune 的 CMO，深度参与来那度胺/髓系产品线的开发与上市——其加盟直接对应 Ofirnoflast 向 LR-MDS 注册性研究推进的需求。这一「创始人科学 + 资深血液学 CMO + 资本型董事长」的组合，是 Halia 相对多数同阶段 Biotech 的治理优势。科学叙事的差异化价值：与多数「先有靶点、再找适应症」的 Biotech 不同，Halia 的出发点是「为何有人带高危基因却不发病」。这种由保护性遗传变异反推可成药通路的逻辑，使其 NEK7 / LRRK2 立项具备天然的人类遗传学背书（human genetic resilience），而非单纯的小鼠表型或生物假设——在监管与资本端都更易建立可信度。二、管线全景 Halia 当前披露四条主线，覆盖血液学、神经、代谢与残余炎症风险，但临床重心明确落在 Ofirnoflast 与 HT-4253 两项。项目模态 / 靶点核心适应症阶段关键状态Ofirnoflast(HT-6184) 口服、别构 NEK7 调节剂（首个） LR-MDS（主线）；肥胖/T2D（联用 semaglutide）；溶血性贫血LR-MDS II 期完成 II 期阳性；FDA Fast Track（2026-06）；EHA2026 口头报告；计划注册性 III 期HT-4253 口服、脑渗透 LRRK2 抑制剂（降 pRab10） APOE4 携带者阿尔茨海默病预防/延迟I 期完成 FIH SAD/MAD 完成（NCT06537817，80 例健康人，无 SAE）；AAIC 2026 海报；拟启患者研究HT-6105 残余炎症风险（降 hsCRP）心血管残余炎症风险早期发现平台延展项目，公开细节有限HT-10068 代谢疾病代谢/炎症交叉适应症早期发现平台延展项目值得注意的是 HT-6184 + Semaglutide 组合：临床前模型显示，NEK7 抑制可增强 GLP-1 受体激动剂的减重效应并保留瘦体重（lean mass）——这指向一个高价值但高度竞争的「代谢炎症（metaflammation）」方向。Halia 据此于 2024 年获诺和诺德 Golden Ticket（进入欧洲生态与战略合作通道），并曾计划 2025 Q3 启动肥胖/T2D 的 IIa 期；该组合的临床推进节奏将是后续重要观察点。三、核心资产 Ofirnoflast（HT-6184）机制深析3.1 靶点生物学：NEK7 是 NLRP3 炎症小体的「装配开关」 NEK7（NIMA-related kinase 7）是 NLRP3 炎症小体组装与激活的必需组分：在钾外流等上游信号触发后，NEK7 与 NLRP3 直接结合，驱动炎症小体多蛋白复合物的形成，进而激活 caspase-1、切割释放 IL-1β 与 IL-18（Shi et al., Nature 2016）。NLRP3–NEK7 复合物的结构于 2019 年被解析，从结构上确认了二者的相互作用界面。关键点在于——阻断 NEK7 等同于在源头「拆台」，而非像传统 NLRP3 催化抑制剂那样仅阻断已形成的炎症小体；Ofirnoflast 更进一步被描述为既能阻止炎症小体形成、又能促进已形成的炎症小体解聚，作用更为上游且可能更彻底。3.2 机制差异化：上游、别构、非细胞因子阻断与下游 IL-1 抗体（canakinumab、rilonacept）或直接 NLRP3 催化抑制剂（selnoflast 等）相比，Ofirnoflast 的「上游 NEK7 别构调节」逻辑有三重潜在优势：其一，同时抑制 IL-1β 与 IL-18 及细胞焦亡（pyroptosis），覆盖更广的炎症效应；其二，通过「重置」炎症小体而非广谱压制免疫，理论上规避广泛免疫抑制；其三，口服给药（vs 注射生物制剂）在慢性病中长期用药的依从性与支付端更友好。这恰是 Halia 反复强调的「靶向慢性炎症根源、而非广谱压制免疫」叙事的科学支点。 Ofirnoflast 的别构结合模式：公司公开将其定义为「allosteric NEK7 modulator」，即非 ATP 竞争性的激酶域别构位点干预。具体共晶/结合口袋细节尚未公开披露，但 NEK7 激酶域已有多个结构可用，为后续结构优化与专利延展提供了基础。对投资人而言，别构位点的「首创（first-in-class）」属性既是护城河，也意味着需要更多临床数据来验证其与催化型 NLRP3 抑制剂的差异化真实幅度。3.3 LR-MDS 中的概念验证：II 期数据解读 LR-MDS 的关键病理是「无效造血（ineffective hematopoiesis）」——NEK7/NLRP3 驱动的慢性炎症破坏骨髓功能、导致贫血与输血依赖；同时 CHIP（克隆性造血）突变（约 70 岁以上 10% 人群）也增加了血液与心血管风险，而 NEK7 抑制被认为可缓解此类克隆炎症。Ofirnoflast 的开放标签、单臂 IIa 期入组 37 例 IPSS-R ≤4.5 的 LR-MDS、ESA 难治/不耐受/不合格患者，方案为 2 mg 口服 QD（5 天给药 / 2 天停）× 最长 32 周，主要终点为 IWG 2018 血液学改善（HI）：指标结果解读总体最佳 HI 率（30 例可评估）67% 多谱系、且突变无关（含 SF3B1、del(5q)） HI-E / HI-P / HI-N 63% / 60% / 60% 红、粒、巨核三系均改善，区别于单系药物输血依赖者（18 例）脱离输血 ≥8 周56% （10 例），中位 28 周，39% 维持 ≥16 周直接对标 luspatercept / imetelstat 的核心终点非输血依赖者（12 例）HI-E 75%（9 例）早线人群同样获益应答者峰值 Hb 升高中位 4.6 g/dL（范围 0.8–7.4）幅度具临床意义安全性无治疗相关 SAE；TRAE 27%（多 G1/2）；G≥3 TRAE 仅 5.4% 耐受性优于细胞毒/部分现有药物这组数据的含金量在于：① 口服、门诊可及；② 多谱系而非单系造血改善；③ 突变无关（mutation-agnostic），不限定 SF3B1 或 del(5q) 亚群；④ 安全性极为干净。其短板是单臂、样本小（n=37）、无对照——这正是 Halia 下一步需通过剂量优化/安全性导入研究（run-in）与注册性随机 III 期来补强的环节。四、财务与现金跑道（私有公司视角） Halia 为私有公司，无公开财报或市值。据披露口径，累计融资约 $42.5M（含 2023-01 A 轮约 $12.2M、2024-03 B/C 轮约 $30M、2025-08 小额追加约 $0.34M），并在 BIO 2026 上明确表示 Series D 进行中。横向看，这一融资体量对任何一家已有两个临床项目（且一项进入后期）的公司都属「偏紧」——直接引申出跑道与再融资风险。财务结构性矛盾：约 $42.5M 的总融资，要同时支撑 Ofirnoflast 的 LR-MDS 注册性推进、HT-4253 的患者研究、以及代谢组合的潜在 IIa 期，资金张力明显。公司历史上依赖「科学叙事 + 战略票据（Golden Ticket）+ 后续轮次」维持推进，这意味着近期高度依赖 Series D 落地与/或大额合作（partnering）。对私募可投性而言，这既是风险，也意味着下一轮估值与条款的弹性空间较大。五、竞争格局5.1 NEK7 直接赛道：相对蓝海在「靶向 NEK7」这一细分里，Halia 几乎是唯一的小分子抑制剂玩家，且进度最前：公司 / 项目模态阶段侧重Halia · Ofirnoflast 别构 NEK7 调节剂（口服）II 期 LR-MDS 主线，血学+系统炎症 Monte Rosa · MRT-8102 NEK7 分子胶降解剂（口服）I 期（2025 IND 清零，2026 H1 入组）心免疫/类风湿/呼吸，二代 CNS 渗透 Rociletinib（老药新用）共价 NEK7（Cys79）临床前/再定位代谢炎症（2 型糖尿病模型） Monte Rosa 的 MRT-8102 是最直接的「同靶点」对照，但模态不同（降解剂 vs 别构抑制剂）且首发聚焦心血管免疫，与 Halia 的 LR-MDS 血学主线错位；其二代 CNS 渗透项目则要 2026 后才 IND。总体看，NEK7 作为独立靶点的拥挤度低（约 2–3 个严肃玩家），Halia 占据「首个临床验证」窗口。5.2 LR-MDS 标准治疗对手（SOV 层面） Ofirnoflast 在 LR-MDS 中实际竞争的是已上市贫血纠正疗法：Luspatercept（BMS, Reblozyl） ——ActRIIB 配体捕获陷阱，COMMANDS 试验确立 ESA-naïve 前线地位；Imetelstat（Geron/Janssen, Rytelo） ——端粒酶抑制剂，IMerge 试验在 ESA 难治/不合格人群实现 39.8% 8 周脱离输血（vs 安慰剂 15.0%）；Lenalidomide （del(5q) 亚群）、Roxadustat（HIF-PHI，跨 ESA-naïve/难治多人群）、以及去甲基化药物（HMA）。 Ofirnoflast 的差异化在于：它是 LR-MDS 领域首个口服、靶向炎症小体根源的机制，且多谱系、突变无关、安全性干净——在 ESA 难治且不宜/不耐受现有药物的患者中具备明确利基。其与 luspatercept/imetelstat 并非简单替代关系，更可能是序贯或联合定位，但最终需头对头或真实世界数据支撑。5.3 阿尔茨海默病 / LRRK2（HT-4253） LRRK2 抑制剂赛道显著拥挤：Denali（DNL201 / DNL343 / beatsonraz）、Biogen、Takeda 等均有布局。HT-4253 凭借「脑渗透 + 靶向 APOE4 携带者预防」的窄切口建立差异化，但进度（刚完成 I 期健康人）远落后于头部，且 AD 预防试验周期长、读数晚，短期不构成价值主线。5.4 广义 NLRP3 抑制剂直接 NLRP3 催化抑制剂赛道拥挤（selnoflast、Inflazome/Roche、Olatec、NodThera、Ventus 等），但 Halia 选择更上游的 NEK7，机制叙事上与之区隔——这也是其在投资者沟通中反复强调的「upstream of NLRP3」定位。六、估值、融资与可投资性作为私有公司，Halia 无可交易股票与公开市值；第三方按行业均值估算的估值参考意义有限（约数千万美元量级，且口径参差）。可投资入口主要为 Series D 私募份额与潜在战略合作/M&A。战略吸引力来自三点：① 已验证的 NEK7 临床概念（LR-MDS 阳性 II 期）；② 「遗传韧性」平台具备可延展多适应症的期权限；③ 炎症小体/残余炎症风险正被大药企重新定价（诺和诺德 Golden Ticket 已是信号）。潜在收购方画像包括诺和诺德（代谢+炎症协同）、以及布局炎症/血液学的 Pfizer、AbbVie、BMS 等。需要提示：私有属性意味着流动性差、信息不透明、估值高度依赖下一轮条款。七、催化剂时间线时间催化剂状态 2026-06 EHA2026 口头报告：Ofirnoflast LR-MDS II 期最终数据已发生 2026-06-15 FDA Fast Track（LR-MDS）已发生 2026 H1–H2 End-of-Phase 2（EOP2）FDA 沟通进行中 2026 剂量优化/安全性导入研究（支持注册性 III 期）计划 2026 HT-4253 阿尔茨海默病患者早期干预研究启动计划（AAIC 2026 海报已出） 2026 Series D 融资完成进行中 2026 H2 HT-6184 + Semaglutide 肥胖/T2D IIa 期（曾计划 2025 Q3）待定/或延后 2026/27 LR-MDS 注册性 III 期启动（若 EOP2 顺利）预期八、风险分析融资/跑道风险（最高）：累计仅约 $42.5M，却要推进两项临床+平台；Series D 落地与否直接决定推进节奏，存在稀释与拖延风险。单资产集中：价值几乎由 Ofirnoflast / LR-MDS 主导；HT-4253 与代谢组合短期难兑现。NEK7 长期安全性未知： NEK7 参与有丝分裂/细胞周期调控，慢性炎症抑制的 on-target 风险（感染、造血、肿瘤学信号）需大型对照试验验证。注册性设计风险： II 期为单臂小样本，FDA 大概率要求随机对照 III 期 + 剂量优化，时间与资金成本高。模态竞争： Monte Rosa 的 NEK7 降解剂若在临床读出上展现更深的「事件驱动」通路抑制，可能重定价 NEK7 赛道。LR-MDS 竞争成熟度： luspatercept/imetelstat 已上市且前线/二线定位稳固，Ofirnoflast 需明确序贯/联合价值。九、投资评估（十维加权）维度评分要点管线质量 / 差异性8.5 首个临床验证的 NEK7 别构调节剂；多谱系、突变无关临床进度7.5 Ofirnoflast II 期阳性；HT-4253 I 期完成机制科学背书8.5 人类遗传韧性起源 + NEK7–NLRP3 已验证生物学知识产权7.5 Ofirnoflast 物质组成专利 + NEK7 别构位点首创财务健康5.5 私有、融资偏紧、Series D 依赖度高竞争格局8.0 NEK7 蓝海；LR-MDS 机制差异化明确估值 / 可投资性6.5 私有不可交易；Series D + M&A 期权风险韧性6.0 单资产 + 融资依赖团队 / 治理7.5 Bearss 连续创业 + 新任 CMO/董事长强化市场空间8.0 LR-MDS + AD + 代谢 + 心免疫炎症可延展加权综合评估：约 7.4 / 10。Halia 的核心价值在于「用已验证的 NEK7 临床概念 + 遗传韧性平台叙事，占据了上游炎症小体赛道的先发窗口」，LR-MDS II 期阳性与 FDA Fast Track 构成近期最强支撑；主要拖累是私有属性下的融资体量偏紧与单资产集中。对私募/战略投资者，它是高科学质量、中等资本确定性的「平台型早期资产」——Series D 条款与后续 EOP2/III 期设计将是估值重估的关键节点。数据来源：Halia Therapeutics 官网与新闻稿、FDA/ClinicalTrials.gov（NCT06537817）、EHA2026 / ASH2025 / AAIC2026 披露、Monte Rosa MRT-8102 公开资料、LR-MDS 标准治疗文献（COMMANDS / IMerge / MEDALIST）、第三方融资数据库（Prospeo / PharnexCloud / TipRanks）。本报告为基于公开信息的非投资建议，Halia 为私有公司，部分财务与估值数据口径有限。

2026-07-16

·Pharma Lobby 播客

FDA批准上市不等于过关：BMS“神药”Krazati为何在III期“翻车”？

点击蓝字关注我们 | 不追时效，只做药厂内部深度审视时事点评药厂门口播客 BMS“神药”Krazati为何在III期“翻车”？ FDA批准上市不等于过关图1 Krazati（Adagrasib），BMS旗下KRAS G12C抑制剂 Introduction 导语 Bristol Myers Squibb（BMS）的KRAS G12C抑制剂Krazati近日遭遇重大挫折。其针对KRAS G12C突变转移性结直肠癌的III期确认性研究KRYSTAL-10未达到无进展生存期（progression-free survival, PFS）和总生存期（overall survival, OS）双主要终点，意味着此前基于加速批准获批的适应症可能面临FDA重新评估。这一结果不仅影响BMS的KRAS布局，也再次引发行业对FDA加速批准制度和KRAS靶向治疗未来发展的讨论。什么是PFS，OS和ORR？无进展生存期（PFS）：从患者开始接受治疗，到肿瘤出现进展（Progression）或患者死亡之间的时间。它回答的是：这款药能够延缓肿瘤再次恶化多久？总生存期（OS）：从患者开始接受治疗，到死亡之间的时间。它回答的是：这款药到底能不能延长患者寿命？客观缓解率（ORR）：接受治疗后，肿瘤体积达到预先规定程度缩小的患者比例。它回答的问题是：有多少患者的肿瘤明显缩小了？ 01 核心要点 1 FDA批准上市，并不意味着"万事大吉" Krazati 在 II 期研究凭借较高的ORR获得 FDA Accelerated Approval，但 III 期确认性研究未能证明患者获得更长的PFS或OS，再次说明加速批准只是"有条件上市"。 2 Krazati失利，不代表KRAS时代结束此次失败仅限于Krazati在KRAS G12C突变结直肠癌中的III期确认性研究，并不影响其肺癌适应症及其他临床开发。更重要的是，它并没有否定KRAS这一靶点的价值，而是意味着第一代KRAS G12C抑制剂完成了"证明KRAS可以成药"的任务，行业竞争正进入如何改善长期生存、克服耐药的新阶段。 3 对BMS而言，这是增长故事受挫，而非基本盘崩塌 Krazati并不是BMS目前最大的收入来源，但它代表着公司在后Opdivo时代的重要增长资产。此次失败削弱的是未来商业潜力，而非当前经营基本面。新闻速览图2 KRYSTAL-10研究结果于ESMO GI 2026大会公布近日，BMS宣布，其KRAS G12C抑制剂Krazati（Adagrasib）联合抗EGFR单克隆抗体（anti-EGFR monoclonal antibody, mAb）西妥昔单抗（Cetuximab）用于治疗KRAS G12C突变转移性结直肠癌（metastatic colorectal cancer, mCRC）的III期确认性临床研究KRYSTAL-10（NCT04793958）未达到共同主要终点。此研究共纳入461例既往接受过治疗的KRAS G12C突变mCRC患者，采用随机对照设计，将Krazati联合Cetuximab与化学疗法（Chemotherapy）进行比较，并以PFS和OS作为共同主要终点。最终结果显示，尽管联合治疗能够使部分患者的肿瘤缩小，并展现出一定的抗肿瘤活性，但无论是无进展生存期（PFS）还是总生存期（OS），均未达到统计学显著性，研究未能证明其能够带来优于标准治疗的长期临床获益。图3 KRYSTAL-10主要终点分析：PFS、OS未达统计学显著性这一结果备受关注，是因为Krazati联合Cetuximab此前已凭借II期KRYSTAL-1研究的数据，于2024年获得FDA Accelerated Approval（加速批准）。当时，研究显示该方案在94名mCRC患者达到约34%的客观缓解，因此FDA允许其基于早期疗效提前上市，并要求企业通过III期确认性研究进一步验证长期临床获益。 KRYSTAL-10的失败意味着，这一确认性研究未能证实Krazati联合Cetuximab能够进一步改善患者长期生存，也再次将FDA加速批准制度、KRAS G12C靶向治疗的临床价值，以及KRAS精准治疗未来的发展方向推向行业讨论的焦点。 02 药物运作原理为什么KRAS G12C成为结直肠癌的重要靶点？ 1 结直肠癌进入精准治疗时代，KRAS成为重要治疗靶点结直肠癌（Colorectal Cancer，CRC）是全球第三大常见癌症，也是癌症相关死亡的第二大原因。仅在美国，美国癌症协会（ACS）预计2026年将新增约15.9万例结直肠癌患者，约5.5万人死于该疾病；更令人担忧的是，结直肠癌已成为50岁以下人群癌症死亡的首要原因之一。随着基因检测技术的普及，医学界逐渐认识到，结直肠癌并不是一种单一疾病，而是一组具有不同分子特征和生物学行为的疾病，因此精准治疗正逐渐成为晚期结直肠癌的重要治疗模式。因此，目前对于晚期或转移性结直肠癌患者（metastatic colorectal cancer, mCRC)，除了传统病理检查外，医生通常还会进行基因检测，根据不同的驱动基因选择不同的精准治疗方案。例如：其中，KRAS是结直肠癌最常见的驱动基因之一，约40%的转移性结直肠癌存在KRAS突变，而KRAS G12C约占其中4%。KRAS突变会持续激活肿瘤细胞增殖相关信号，使癌细胞不断生长，因此长期以来一直被认为是极具潜力的治疗靶点。然而，由于KRAS蛋白结构特殊，过去几十年一直被认为是"不可成药（undruggable）"靶点，直到第一代KRAS G12C抑制剂问世，才真正打开了KRAS精准治疗的大门。 2 KRAS G12C抑制剂如何发挥作用？ KRAS可以理解为细胞内控制生长的"总开关"，正常情况下，它会不断在两种状态之间切换： ON状态（结合GTP）：激活MAPK等信号通路，促进细胞生长和分裂； OFF状态（结合GDP）：关闭增殖信号，使细胞恢复正常状态。健康细胞中，这种"开—关"循环受到严格调控。但当KRAS发生G12C突变后，这个开关更容易保持在"开启（ON）"状态，导致下游MAPK信号持续激活，癌细胞不断接收到"继续增殖"的指令，从而推动肿瘤发生和发展。图4 KRAS G12C抑制剂将KRAS锁定于OFF状态，抑制肿瘤信号通路第一代KRAS G12C抑制剂，如已经经过FDA批准的Amgens的Lumakras（Sotorasib）和本文提到的BMS的Krazati（Adagrasib）正是利用了这一突变的特殊结构。虽然KRAS G12C更倾向于保持ON状态，但它仍会短暂回到OFF状态。KRAS G12C抑制剂会利用OFF时刻与KRAS形成共价结合（covalent binding），并将其"锁定"在失活状态，使KRAS无法再次被激活，从而切断MAPK等促肿瘤信号通路。第一代KRAS G12C抑制剂的出现具有重要意义——它们首次证明了KRAS这一长期被认为"不可成药"的靶点，可以通过小分子药物进行精准靶向治疗。目前除了上面提到的两个FDA批准的KRAS G12C抑制剂外，还有多款新一代KRAS/RAS靶向药物正在开发中，例如Divarasib、Olomorasib，以及能够直接靶向KRAS活化状态（ON）的RMC-6291等。图5 Adagrasib通过共价结合特异性靶向KRAS G12C突变蛋白 03 上市，并不是终点 Krazati III期失败背后的FDA加速批准制度为何Krazati能仅凭II期数据获批上市？对于很多人来说，一个最大的疑问是：为什么Krazati在没有完成III期临床试验的情况下，就已经获得FDA批准上市？答案在于FDA的Accelerated Approval制度。Accelerated Approval设立于1992年，最初是为了应对艾滋病危机，后来逐渐扩展至肿瘤等严重疾病领域。其核心理念是：对于缺乏有效治疗选择、存在重大未满足医疗需求（Unmet Medical Need）的疾病，如果药物已经显示出较强的早期疗效，即使尚未证明能延长患者生存，也可以提前让患者获得治疗机会。因此，FDA允许企业依据替代终点（Surrogate Endpoints），例如客观缓解率（ORR）和缓解持续时间（DoR）等指标申请上市，而无需等待耗时数年的III期临床试验结果。 Krazati联合Cetuximab正是基于II期KRYSTAL-1研究获得FDA加速批准。当时研究显示，该方案的ORR达到34%，中位无进展生存期（PFS）约为6.9个月。对于治疗选择十分有限的KRAS G12C突变转移性结直肠癌患者而言，这一结果已经具有明确的临床意义，因此FDA决定授予其Accelerated Approval。图6 KRYSTAL-1 II期研究：联合治疗较单药显著提高ORR，并延长DoR和PFS 加速批准，不等于最终批准 Accelerated Approval并不是最终批准，而是一种"先上市、后验证"的监管机制。获得加速批准后，企业仍需开展确认性III期临床试验（Confirmatory Trial），验证早期疗效是否能够真正转化为患者长期获益。对于肿瘤药物而言，这类研究通常采用随机对照设计，以当前标准治疗作为对照，并以PFS和OS作为主要终点。只有证明药物能够改善这些临床终点，加速批准才能转为传统批准（Traditional Approval）；否则，FDA有权撤回相关适应症。换句话说，Accelerated Approval更像是一张"临时通行证"，它允许患者提前获得潜在有效的新疗法，但药企仍需通过后续III期研究完成真正的"毕业考试"。为什么II期成功，III期却失败？ KRYSTAL-10 III期的失败并不意味着II期研究"错了"，而是因为II期和III期本身回答的是两个不同层次的问题。首先，两项研究采用了不同的疗效评价标准。II期研究主要评估药物是否具有抗肿瘤活性，因此通常关注ORR和缓解持续时间（DoR）等替代终点；而III期确认性研究真正希望回答的是，这些早期疗效能否最终转化为患者长期获益，也就是无进展生存期（PFS）和总生存期（OS）的改善。其次，两项研究的设计也存在本质差异。支持FDA加速批准的KRYSTAL-1属于单臂研究，没有标准治疗对照，因此只能说明Krazati联合Cetuximab具有临床活性；而KRYSTAL-10则是一项随机对照III期研究，直接将联合治疗与当前标准治疗进行比较，评价标准也更加严格。只有证明新方案能够优于标准治疗，才能完成从加速批准到传统批准的转换。从FDA监管的角度来看，这也正是确认性III期临床试验存在的意义——验证早期疗效是否真正能够转化为长期临床获益，确保药物最终带给患者的不只是影像学上的改善，而是真实、可持续的生存获益。 04 KRYSTAL-10的失败，是否意味着KRAS时代结束？ Q 为什么Krazati在治疗肺癌成功，结直肠癌却那么难？虽然KRAS G12C抑制剂成功攻克了这一长期"不可成药"的靶点，但在结直肠癌中的疗效却没有肺癌那么理想。原因在于，结直肠癌并不是单纯依赖KRAS这一条信号通路。可以把肿瘤细胞想象成一座城市，KRAS就像其中的一条主干道。当KRAS被药物封锁后，肿瘤细胞很快会打开另一条"备用道路"——EGFR信号通路，重新激活下游MAPK信号，使癌细胞恢复生长。当KRAS G12C被药物封锁后，肿瘤细胞会迅速增强EGFR信号，并重新激活野生型RAS（Wild-type RAS），最终再次启动下游MAPK信号通路，使癌细胞恢复生长。这种现象被称为EGFR反馈激活（EGFR feedback activation），也是KRAS G12C抑制剂在结直肠癌中最重要的耐药机制之一。因此，目前主流研发策略已经从单独抑制KRAS，发展为KRAS抑制剂联合EGFR抗体（如Cetuximab或Panitumumab），希望同时阻断两条关键信号通路，延缓耐药的发生。这一策略显著提高了患者的ORR和PFS，并促成了Krazati联合Cetuximab获得FDA加速批准，用于KRAS G12C突变转移性结直肠癌患者。然而，KRYSTAL-10 III期研究的失败也说明，即使联合抑制EGFR，仍然未能证明患者能够获得更长的PFS和OS获益。图7 KRAS G12C被抑制后，EGFR反馈激活可重新激活野生型RAS（WT RAS），恢复下游MAPK信号通路 2 KRYSTAL-10失败后，KRAS治疗将走向何方？尽管KRYSTAL-10未能证实Krazati联合Cetuximab能够进一步改善患者的PFS和OS，但这并不意味着KRAS靶向治疗走到了终点。事实上，这项研究反而为整个行业指出了下一阶段的发展方向。首先，联合治疗仍将是KRAS精准治疗的核心策略。目前研究已经证明，单独抑制KRAS很容易受到EGFR反馈激活等耐药机制的影响。因此，未来不仅会继续探索KRAS抑制剂联合EGFR抗体，还将进一步尝试联合SHP2抑制剂和SOS1抑制剂——这两类药物分别作用于KRAS上游信号传导过程中的关键节点，能够进一步阻断EGFR向RAS-MAPK通路传递生长信号。此外，联合免疫治疗、化疗等多种策略也正在积极探索，希望更全面地抑制RAS-MAPK信号通路，延缓耐药的发生。其次，KRAS靶向治疗正在逐渐从晚线治疗向更早期治疗前移。目前Krazati和Lumakras联合EGFR抗体主要用于二线及以后治疗，但越来越多临床研究正在探索将KRAS靶向治疗应用于一线治疗，甚至与标准化疗联合使用，希望在疾病进展更早期就控制肿瘤，提高长期生存获益。更重要的是，KRAS G12C只是整个RAS研发的起点，而不是终点。 KRAS G12C突变仅占全部KRAS突变的一小部分，目前已有多款针对KRAS G12D、多种KRAS突变（Multi-KRAS）以及整个RAS家族（Pan-RAS）的新一代药物进入临床开发。例如，Revolution Medicines开发的Pan-RAS抑制剂Daraxonrasib（RMC-6236）以及多款KRAS G12D抑制剂，都代表着KRAS精准治疗的下一阶段发展方向。因此，KRYSTAL-10的失败，更像是第一代KRAS G12C抑制剂发展过程中的一次重要经验，而不是KRAS靶向治疗的终点。第一代KRAS G12C抑制剂已经完成了"证明KRAS可以成药"的历史使命，未来行业竞争的重点，将从"能否抑制KRAS"，转向"如何建立更有效的联合治疗策略、覆盖更多RAS突变，并真正改善患者的长期生存"。图8 KRAS G12C只是起点，下一代RAS药物研发正向整个RAS-MAPK信号通路延伸 05 KRYSTAL-10失败，对BMS和整个KRAS赛道意味着什么？一、为什么BMS愿意花48亿美元（约57亿美元企业价值）收购Mirati？作为全球最大的创新药公司之一，BMS的研发管线覆盖肿瘤、血液、免疫、心血管和神经科学等多个领域，其中肿瘤业务始终是公司的核心增长引擎。凭借PD-1抑制剂Opdivo（nivolumab）、CTLA-4抑制剂Yervoy（ipilimumab）以及PD-1/LAG-3双免疫疗法Opdualag，BMS长期占据全球肿瘤免疫治疗市场的重要地位。然而，随着Opdivo等重磅产品逐步接近专利悬崖（Patent Cliff），寻找下一代增长引擎成为BMS近年来最重要的战略任务之一。正是在这样的背景下，BMS于2023年底宣布以约48亿美元（约57亿美元企业价值）收购Mirati Therapeutics，希望进一步强化精准肿瘤治疗布局。在官方投资者材料中，Krazati被明确定位为"Best-in-class KRAS G12C inhibitor"，不仅看重其已获批的肺癌适应症，更期待其向结直肠癌、一线非小细胞肺癌及其他实体瘤持续拓展适应症。同时，Mirati还拥有覆盖整个RAS通路的研发管线，包括KRAS G12D抑制剂MRTX1133、SOS1抑制剂MRTX0902以及PRMT5抑制剂MRTX1719。正如BMS在收购公告中所说，这笔交易的目标是"Strengthen and diversify our oncology portfolio"，打造未来十年的肿瘤创新管线。这笔收购还有一个重要背景。2021年，Amgen推出全球首个KRAS G12C抑制剂Lumakras（sotorasib），首次证明了KRAS这一曾被认为"不可成药"数十年的靶点可以被成功靶向，也验证了KRAS赛道的科学可行性和商业价值。对BMS而言，收购Mirati并非简单追随Amgen，而是在KRAS完成概念验证（Proof of Concept）之后，押注一款有望成为Best-in-class的产品。当时，Krazati凭借更优的药代动力学特性、较好的脑转移渗透能力以及在结直肠癌中的早期临床数据，被市场认为具备超越Lumakras的潜力。因此，BMS真正押注的并不仅仅是Krazati，而是一个覆盖KRAS G12C、KRAS G12D乃至整个RAS家族的长期研发平台，以及由此带来的持续适应症扩展和商业增长潜力。图9 BMS官方将Mirati定位为强化肿瘤管线和推动长期增长的重要战略资产二、 KRYSTAL-10失败，对BMS而言是一场重大打击吗？如果只看临床结果，KRYSTAL-10无疑是一项令人失望的III期研究。但对于BMS而言，这并不意味着整个Krazati项目已经失败。首先，BMS官方并没有将KRYSTAL-10定义为"Krazati失败"。在回应媒体采访时，公司发言人表示："While the study did not meet its primary endpoints, results from the final analysis of the study presented at ESMO GI support the clinical activity of the adagrasib plus cetuximab combination in this patient population." 也就是说，尽管研究未达到PFS和OS等主要终点，但最终分析结果仍支持Krazati联合Cetuximab在该患者群体中具有抗肿瘤活性（clinical activity）。对于BMS而言，KRYSTAL-10否定的并不是Krazati的作用机制，而是现有治疗策略尚未证明能够转化为长期生存获益。更重要的是，此次受挫仅限于结直肠癌适应症，并不代表整个Krazati项目的失败。目前，Krazati已获批用于KRAS G12C突变非小细胞肺癌（NSCLC），相关商业化仍在继续，肺癌领域的两项关键III期研究——KRYSTAL-7和KRYSTAL-4——也将按照计划推进。这说明，BMS依然看好KRAS G12C抑制剂在肺癌中的临床价值，此次失败更多反映的是结直肠癌复杂的生物学特点，而非Krazati本身失去竞争力。不过，KRYSTAL-10仍然给BMS带来了实质性影响。真正受到冲击的，是Krazati通过不断拓展适应症（Label Expansion）释放商业价值的增长逻辑。结直肠癌曾是BMS收购Mirati时重点布局的适应症之一，而此次III期失败意味着这一关键增长机会的不确定性显著增加，也限制了Krazati未来的市场空间。因此，对于BMS而言，KRYSTAL-10削弱的是Krazati的增长故事（Growth Story），而不是公司的经营基本盘。目前，BMS仍拥有Opdivo、Yervoy、Opdualag、Reblozyl、Breyanzi、Camzyos、Cobenfy等多款商业化产品支撑收入，Krazati并非公司的核心现金流来源。但作为"后Opdivo时代"精准肿瘤战略的重要资产，它未来的商业预期无疑变得更加谨慎。图10 KRYSTAL-10的失败仅限于结直肠癌适应症，Krazati肺癌III期项目仍在继续推进三、KRYSTAL-10给整个行业带来了什么启示？ KRYSTAL-10的意义，并不仅仅在于一项III期临床研究的失败。它再次提醒整个行业，在精准医疗时代，找到一个有效的药物靶点，只是创新药研发的起点；真正决定一款药物商业价值和临床价值的，是它能否最终改善患者的长期生存。过去十年，精准医疗的发展重点是不断发现新的驱动基因（Driver Mutation）和生物标志物（Biomarker），并开发相应的靶向药物。而随着越来越多靶点被成功"攻克"，行业竞争的焦点也正在发生变化。从"能不能开发出靶向药"，逐渐转向"谁能够真正延长患者生存"。对于FDA而言，Accelerated Approval始终是在尽早满足患者治疗需求与确保疗效真实可靠之间寻找平衡。监管机构允许药物基于早期疗效提前上市，但最终仍需要确认性III期研究证明，这些早期疗效能够真正转化为PFS和OS的改善。而对于整个产业而言，KRYSTAL-10释放出的信号则更加深远。未来，创新药的竞争优势将不仅来自于是否拥有一个新的靶点，更来自于是否能够建立一套完整的临床开发策略——包括如何选择真正能够获益的患者人群、如何设计更合理的联合治疗方案，以及如何克服耐药机制，使短期的肿瘤缓解最终转化为长期生存获益。从商业角度来看，这也意味着资本市场评估创新药的标准正在发生变化。过去，一项漂亮的II期数据往往足以支撑数十亿美元的交易和巨额市场预期；而未来，投资者将更加关注药物能否顺利完成确认性III期研究，能否实现适应症扩展（Label Expansion），以及能否建立可持续的临床竞争优势。真正创造价值的，不再是"First-in-class"的概念，而是能够持续证明临床获益、不断拓展适应症的"Best-in-class"产品。图11 未来创新药的竞争优势，将不仅来自靶点创新，更来自持续证明临床获益并实现适应症扩展 Daniel 有话药说 Krazati失败，不代表KRAS失败。如果把过去十年的KRAS研发放在一起看，就会发现真正发生的事情其实是：第一代KRAS G12C抑制剂完成了自己的历史使命——证明KRAS并非"不可成药"。而今天，整个行业已经进入新的竞争阶段。未来决定胜负的，不再是谁最早上市，而是谁能够真正拿出长期生存获益的数据。 Krazati在结直肠癌的失败，更像是KRAS赛道的一次升级信号：从"证明靶点可成药"，走向"证明能够改变患者生存"。同时，FDA加速批准不是"免考"，而是"先上车，后补票"。二期数据让药物提前上市，但真正决定它能否长期留在市场上的，仍然是后续确认性III期临床试验。只有证明患者真的活得更久、疾病控制得更久，加速批准才能转为正式批准；否则，适应症仍有可能被撤销。撰稿: Daniel有话药说, Wendy 排版编辑: Wendy, Dan 校对: Sophie, 大树, Mia, Dan, Jay 版权归药厂门口播客所有 INVITATION 播客联动我们每两周会从当期发布的4篇行业新闻中，选择讨论热度最高的一篇，在播客《药厂门口》中继续深聊。如果你希望我们继续聊这条新闻，欢迎留言说说你的看法。求点赞求分享求喜欢

100 项与罗特西普相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	罗特西普	B03XA06	DB12281

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
非输血依赖性地中海贫血	欧盟	Bristol-Myers Squibb Pharma EEIG	2023-03-20
非输血依赖性地中海贫血	冰岛	Bristol-Myers Squibb Pharma EEIG	2023-03-20
非输血依赖性地中海贫血	列支敦士登	Bristol-Myers Squibb Pharma EEIG	2023-03-20
非输血依赖性地中海贫血	挪威	Bristol-Myers Squibb Pharma EEIG	2023-03-20
贫血	韩国	Bristol Myers Squibb Co.	2022-05-09
铁粒幼细胞性贫血	欧盟	Bristol-Myers Squibb Pharma EEIG	2020-06-25
铁粒幼细胞性贫血	冰岛	Bristol-Myers Squibb Pharma EEIG	2020-06-25
铁粒幼细胞性贫血	列支敦士登	Bristol-Myers Squibb Pharma EEIG	2020-06-25
铁粒幼细胞性贫血	挪威	Bristol-Myers Squibb Pharma EEIG	2020-06-25
骨髓增生异常综合征	欧盟	Bristol-Myers Squibb Pharma EEIG	2020-06-25
骨髓增生异常综合征	冰岛	Bristol-Myers Squibb Pharma EEIG	2020-06-25
骨髓增生异常综合征	列支敦士登	Bristol-Myers Squibb Pharma EEIG	2020-06-25
骨髓增生异常综合征	挪威	Bristol-Myers Squibb Pharma EEIG	2020-06-25
输血依赖性贫血	欧盟	Bristol-Myers Squibb Pharma EEIG	2020-06-25
输血依赖性贫血	冰岛	Bristol-Myers Squibb Pharma EEIG	2020-06-25
输血依赖性贫血	列支敦士登	Bristol-Myers Squibb Pharma EEIG	2020-06-25
输血依赖性贫血	挪威	Bristol-Myers Squibb Pharma EEIG	2020-06-25
输血依赖性β地中海贫血	欧盟	Bristol-Myers Squibb Pharma EEIG	2020-06-25
输血依赖性β地中海贫血	冰岛	Bristol-Myers Squibb Pharma EEIG	2020-06-25
输血依赖性β地中海贫血	列支敦士登	Bristol-Myers Squibb Pharma EEIG	2020-06-25

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
骨髓纤维化	临床3期	中国	Celgene Corp.	2022-02-23
真性红细胞增多症	临床3期	中国	Celgene Corp.	2022-02-23
原发性血小板增多症	临床3期	中国	Celgene Corp.	2022-02-23
真性红细胞增多症后骨髓纤维化	临床3期	美国	Celgene Corp.	2021-02-25
真性红细胞增多症后骨髓纤维化	临床3期	中国	Celgene Corp.	2021-02-25
真性红细胞增多症后骨髓纤维化	临床3期	日本	Celgene Corp.	2021-02-25
真性红细胞增多症后骨髓纤维化	临床3期	阿根廷	Celgene Corp.	2021-02-25
真性红细胞增多症后骨髓纤维化	临床3期	澳大利亚	Celgene Corp.	2021-02-25
真性红细胞增多症后骨髓纤维化	临床3期	奥地利	Celgene Corp.	2021-02-25
真性红细胞增多症后骨髓纤维化	临床3期	比利时	Celgene Corp.	2021-02-25

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04717414 (INDEPENDENCE, CTgov)	临床3期	贫血 \| 真性红细胞增多症后骨髓纤维化 \| 原发性骨髓纤维化	313	Luspatercept (Treatment)	鬱衊獵襯衊憲鑰鏇選遞 = 淵糧觸鑰襯鏇網艱膚憲積廠蓋窪網積構醖鏇鏇 (襯製淵願鹹衊壓淵鹽膚, 壓鹹鏇願築襯醖壓膚糧 ~ 積簾觸夢蓋襯構鏇廠廠) 更多	-	2026-07-16
				Placebo+Luspatercept (Control)	鬱衊獵襯衊憲鑰鏇選遞 = 獵範選製憲襯鏇觸鬱繭積廠蓋窪網積構醖鏇鏇 (襯製淵願鹹衊壓淵鹽膚, 壓積憲蓋醖簾網艱鏇鑰 ~ 願蓋淵觸繭鬱憲鹹鹹繭) 更多
ASCO2026	N/A	骨髓增生异常综合征	1,602	Luspatercept (Prior ESA-exposed)	襯製構憲網築淵網遞遞(觸衊壓鏇鬱糧廠築膚積) = 襯艱艱齋構鬱醖窪獵構壓鑰簾顧窪鏇衊鑰積蓋 (觸觸觸觸觸壓艱憲醖窪 ) 更多	积极	2026-05-29
				Luspatercept (ESA-naive)	襯製構憲網築淵網遞遞(觸衊壓鏇鬱糧廠築膚積) = 簾廠廠遞鹽構簾夢顧觸壓鑰簾顧窪鏇衊鑰積蓋 (觸觸觸觸觸壓艱憲醖窪 ) 更多
NCT03682536 (COMMANDS, ASCO2026)	临床3期	骨髓增生异常综合征一线	363	Luspatercept	淵壓遞鬱鬱窪願醖蓋顧(範襯夢顧鹽鏇蓋鹽醖齋) = 獵範獵夢獵鬱顧壓齋鹽壓蓋製選積壓廠衊窪窪 (鏇鏇繭淵鏇範齋憲簾選 ) 更多	积极	2026-05-29
				Epoetin alfa	淵壓遞鬱鬱窪願醖蓋顧(範襯夢顧鹽鏇蓋鹽醖齋) = 鑰壓齋膚觸糧鏇簾鏇繭壓蓋製選積壓廠衊窪窪 (鏇鏇繭淵鏇範齋憲簾選 ) 更多
NCT03682536 (COMMANDS, EHA2026)	临床3期	骨髓增生异常综合征	203	Luspatercept (lower-risk myelodysplastic syndromes + ESA-naive + transfusion-dependent)	鏇築築獵構艱憲範糧築(製製膚糧蓋蓋積淵獵襯) = 醖鬱範製襯蓋艱鏇壓齋鹹獵糧鹹網繭憲膚構窪 (遞餘醖觸繭範廠餘齋繭 ) 更多	积极	2026-05-21
				Epoetin alfa (lower-risk myelodysplastic syndromes + ESA-naive + transfusion-dependent)	鏇築築獵構艱憲範糧築(製製膚糧蓋蓋積淵獵襯) = 鬱衊醖餘鏇繭窪鑰鑰獵鹹獵糧鹹網繭憲膚構窪 (遞餘醖觸繭範廠餘齋繭 ) 更多
EHA2026	N/A	贫血	16	Luspatercept + LuspaterceptIron supplementation (for iron deficiency)	蓋壓鬱製窪積鏇齋鹹鏇(構構窪窪築夢鏇築構鹽) = 艱艱鬱範齋鑰壓範築夢蓋糧艱遞醖廠鑰夢觸膚 (鹽壓鑰壓窪夢積憲窪製 ) 更多	积极	2026-05-12
NCT04717414 (INDEPENDENCE, EHA2026)	临床3期	-	313	LUSPA + JAKi	網餘壓襯顧簾蓋壓艱繭(遞艱鏇鹽糧蓋艱糧糧簾) = 簾顧醖夢鏇廠鬱簾廠願憲構鑰壓鹹憲網獵觸鏇 (鹹願餘簾積窪製繭獵網 ) 更多	积极	2026-05-12
				Placebo + JAKi	網餘壓襯顧簾蓋壓艱繭(遞艱鏇鹽糧蓋艱糧糧簾) = 構蓋餘衊襯鏇鹽鑰選醖憲構鑰壓鹹憲網獵觸鏇 (鹹願餘簾積窪製繭獵網 ) 更多
NCT06045689 (MAXILUS, EHA2026)	临床3期	骨髓增生异常综合征	106	LUSPATERCEPT 1.75 mg/kg	鏇膚艱衊積網鏇廠蓋鏇(繭積鏇選構範鏇齋鏇膚) = 膚廠壓積壓觸窪淵遞糧積鏇壓鏇鏇夢鏇製顧繭 (衊醖膚鏇壓鏇積糧壓壓 ) 更多	积极	2026-05-12
				LUSPATERCEPT 1.75 mg/kg	鏇膚艱衊積網鏇廠蓋鏇(繭積鏇選構範鏇齋鏇膚) = 夢鏇醖壓獵願構鑰膚鹹積鏇壓鏇鏇夢鏇製顧繭 (衊醖膚鏇壓鏇積糧壓壓 ) 更多
EHA2026	N/A	骨髓增生异常综合征	150	Luspatercept	鑰窪簾餘鏇壓選餘膚淵(獵構壓鹹壓遞夢衊糧淵) = 醖簾廠襯範構顧鬱壓廠餘窪製獵簾窪壓壓窪糧 (壓顧築艱鑰鹹衊蓋壓顧 ) 更多	积极	2026-05-12
REACH (EHA2026)	N/A	骨髓增生异常综合征	88	Luspatercept	廠壓願積顧襯鹹構衊鏇(夢窪顧繭鹹築網製範齋) = 獵淵積壓遞繭餘顧鬱鏇選選醖膚齋膚製壓繭觸 (繭遞齋鹹衊憲選積膚襯 ) 更多	积极	2026-05-12
NCT05399732 (Pubmed \| BMC Med)	临床2期	再生障碍性贫血	58	Cyclosporine + Luspatercept	選製艱遞遞願壓餘構願(醖淵鑰簾鹹範膚夢淵構) = 製憲壓繭鑰膚遞淵鏇襯繭獵鹽鹹夢選網範網鹽 (壓夢鑰選範願積鏇淵憲 ) 更多	积极	2026-04-29
				Cyclosporine	選製艱遞遞願壓餘構願(醖淵鑰簾鹹範膚夢淵構) = 膚鑰艱衊衊鹽繭齋鏇糧繭獵鹽鹹夢選網範網鹽 (壓夢鑰選範願積鏇淵憲 ) 更多