Chikungunya virus vaccine (Valneva)

Nature Medicine Volume 32 Issue 2, February 2026 @本期速览 2026年2月《Nature Medicine》第32卷第2期精彩上线！🧬 这期聚焦机制驱动的临床转化，带来AI医疗、感染防控、神经退行性疾病、肿瘤精准治疗与代谢健康等多领域重磅发现，让读者一览全球最新科学脉动。 社论直指神经退行性疾病需更多机制指导的试验，以扭转近期高调失败局面。神经领域亮点频现：毛细血管干血斑检测精准捕捉阿尔茨海默病标志物p-tau217，为大规模筛查与远程评估铺路🧠；单剂短效DMT迷幻药结合心理支持，快速持久缓解重度抑郁症状。 感染病与疫苗研究同样振奋人心！科学家“反击”莱姆病，重思抗生素、新疫苗与疗法；PD-1阻断重编程HIV免疫，显著减少病毒储存库；新型低毒噁唑烷酮有望广谱治疗结核；儿童减毒活基孔肯雅疫苗安全有效。非洲农村凉屋顶+防蚊改造兼顾降温与疟疾控制，85%居民愿自费推广🌡️。 AI医疗成为本期最大亮点🤖：视角提出上下文切换范式，让医疗AI自动适应不同场景；定制大型语言模型助力复杂心脏病管理，优于医师独立决策；但随机试验警示，LLM作为公众助手时人类表现反不及模型独立水平。多模态睡眠基础模型仅凭一夜记录即可预测130种疾病风险，包括死亡与痴呆。 肿瘤精准医学捷报连连：repotrectinib在NTRK融合瘤中获持久全身及颅内应答；日本5万+真实世界数据显示综合基因组分析效用因肿瘤类型差异巨大；Abemaciclib显著延长NF2/CDK改变脑膜瘤无进展生存；可溶性MAdCAM-1成转移性肾癌生存强预后标志。 代谢与慢性病管理同样务实：替尔泊肽改善阻塞性睡眠呼吸暂停心代谢风险；23,634人研究鉴定235种代谢物关联2型糖尿病未来风险；血液标志物揭示多重疾病核心代谢通路；基层PATHWEIGH干预助力体重管理；微创妇科手术零阿片处方疼痛控制不减。 此外，津巴布韦Y-Check青少年健康检查可行且受欢迎；全球药物滥用负担持续攀升，尤其美国；低剂量IL-2降低急性冠脉炎症。 @本期启示 1| 如何将机制洞见更有效地融入复杂疾病的临床试验设计？未来研究应聚焦构建“机制-表型-结局”三维映射框架，利用单细胞多组学与AI模拟提前预测试验成败，推动从经验驱动转向精准机制验证的试验范式转变。 2| 医疗人工智能如何实现跨临床场景、人群与系统的可靠泛化？需重点探索上下文切换与多模态动态适配技术，结合真实世界持续学习机制，开发可解释性评估体系，确保AI在不同地域、资源条件下的安全落地与公平应用。 3| 循环生物标志物如何成为预测与干预多重慢性疾病的核心工具？未来方向是建立动态炎症-代谢图谱数据库，整合遗传、生活方式与环境数据，开发个体化风险轨迹模型，为早期多靶点干预提供精准指引。 4| 主观体验与神经可塑性在精神疾病治疗中的因果关系如何被科学解析？应设计严谨的“体验-脑网络-长期结局”纵向研究，结合非致幻类似物对照与实时神经成像，阐明快速抗抑郁机制，为新型精神治疗药物研发奠定理论基础。 5| 气候变化与传染病双重压力下，环境干预如何同时实现健康适应与疾病防控？研究需转向可持续住房与社区改造的整合试验，量化热应激、媒介控制与心理健康的协同效应，开发低成本、可推广的“一揽子”气候-健康解决方案。 6| 非药物神经调控与期望机制能否成为免疫增强和慢性病管理的新路径？未来应开展大规模随机对照研究，探索神经反馈、心理干预与疫苗/治疗协同作用，揭示脑-免疫轴的调控规律，为无药或减药方案提供循证依据。 7| 在全球多样人群中，精准医学如何平衡基因组数据与本地化临床效用？需建立多祖先、多组学共享平台，开发 ancestry-aware 的风险预测与治疗决策工具，推动从欧美中心向全球公平覆盖的转化研究转型。 8| 新兴疫苗与抗感染疗法如何应对耐药与储存库难题，实现长效根治？研究重点应放在多价广谱候选物筛选、储存库重编程机制解析以及联合疗法优化上，加速从控制感染向功能性治愈的战略升级。 @本期内容 Editorial1| Neurodegenerative diseases need more mechanism-informed trials 神经退行性疾病需要更多基于机制的临床试验 Recent failures in high-profile clinical trials of neurodegenerative diseases highlight the need to rebalance clinical ambition and biological understanding. 近期神经退行性疾病高调临床试验的多次失败凸显出需要在临床雄心与生物学理解之间重新取得平衡。 News2| Biting back at Lyme diseaseMay, Mike 反击莱姆病 As case numbers rise, scientists are rethinking existing antibiotics, alongside new vaccines and therapies, to prevent or treat infections and to confront the persistence of post-treatment illness. 随着病例数上升，科学家们正在重新思考现有抗生素，同时开发新疫苗和疗法，以预防或治疗感染，并应对治疗后疾病的持续存在。 News Feature3| Fault lines in a global promiseAdepoju, Paul 全球承诺中的裂痕 The promise was global. The fracture, when it came, was painfully local. 承诺是全球性的。而裂痕到来时，却令人痛苦地显现为地方性的。 Correspondence4| The Translational Research and Innovation Laboratory (TRAIL) model for accelerating discovery through a shared institutional resourceBruzek, Steven, Vestal, Grant, Morrison, John, et al. 通过共享机构资源加速发现的转化研究与创新实验室（TRAIL）模式 [No short summary] [无短摘要] 5| Disentangling climate hazards from demographic change in climate–health projectionsKephart, Josiah L., Bilal, Usama 在气候-健康预测中区分气候危害与人口变化 [No short summary] [无短摘要] 6| China’s evidence-based re-evaluation of traditional Chinese medicine injectionsChen, Chen, Hou, Ziwei 中国对中药注射剂的循证再评价 [No short summary] [无短摘要] 7| Reorienting Ebola care toward human-centered sustainable practiceOmasumbu, Richard Kitenge, Fontana, Luca, le Polain de Waroux, Olivier, et al. 将埃博拉护理重新导向以人为中心可持续实践 [No short summary] [无短摘要] 8| Lessons from Rwanda’s response to the Marburg virus outbreakNsanzimana, Sabin, Butera, Yvan, Nkeshimana, Menelas, et al. 卢旺达应对马尔堡病毒暴发的经验教训 [No short summary] [无短摘要] World View9| US vaccine policy must put America firstRasmussen, Angela L. 美国疫苗政策必须把美国放在首位 Aligning US vaccine policy with that of other countries ignores what is best for Americans. 将美国疫苗政策与其他国家对齐，忽视了对美国人最有利的内容。 Comment10| Building a code of conduct for AI-driven clinical consultationsLim, Ernest, Thirunavukarasu, Arun, He, Yajie Vera, et al. 构建人工智能驱动临床咨询的行为准则 Can clinical artificial intelligence borrow from the experience of developing safe autonomous vehicles to develop safe autonomous consultations for medicine? 临床人工智能能否借鉴开发安全自动驾驶汽车的经验，来开发医学中安全的自主咨询？ 11| How to interpret ‘zero-shot’ results from generative EHR modelsBedi, Suhana, Fries, Jason Alan, Shah, Nigam H. 如何解读生成式EHR模型的“零样本”结果 Generative models trained on electronic health records are viewed as ‘zero-shot predictors’ for clinical outcomes — but this interpretation is misleading. 在电子健康记录上训练的生成模型被视为临床结局的“零样本预测器”——但这种解读具有误导性。 12| The ethics of multi-cancer screeningCallender, Thomas, Mackie, Anne, Slowther, Anne-Marie 多癌种筛查的伦理问题 Multi-cancer detection tests offer a new paradigm in cancer screening — the use of a single test to simultaneously screen for many cancers — but they raise important ethical questions for their development, evaluation and possible implementation. 多癌种检测测试为癌症筛查提供了新范式——使用单一测试同时筛查多种癌症——但其开发、评估和可能的实施引发了重要的伦理问题。 13| Identifying ultra-processed foods for policyMoran, Alyssa J., Khandpur, Neha, Roberto, Christina A. 为政策识别超加工食品 Defining non-ultra-processed foods, rather than ultra-processed foods, would better protect the public’s health. 界定非超加工食品，而非超加工食品，将更好地保护公众健康。 News & Views14| Housing modifications for heat adaptationMshamu, Salum, von Seidlein, Lorenz, Knudsen, Jakob Brandberg 住房改造用于热适应 A randomized controlled trial illustrates the challenges of passive cooling in hot humid Africa, where temperatures are rising and millions of new housing units will be needed by the middle of the century. 一项随机对照试验展示了炎热潮湿非洲地区被动冷却的挑战，那里气温正在上升，到本世纪中叶将需要数百万新的住房单元。 15| Placebo effect influences vaccine responsesKim, Kyungdeok, Title, Ben, Kipnis, Jonathan 安慰剂效应影响疫苗应答 A randomized trial provides direct human evidence that the placebo effect can shape humoral immunity, showing that reward-related brain activity correlates with vaccine-induced antibody production and opening new avenues for treating many medical conditions. 一项随机试验提供了直接的人类证据，证明安慰剂效应可以塑造体液免疫，显示与奖励相关的脑活动与疫苗诱导的抗体产生相关，并为治疗多种医学疾病开辟了新途径。 16| Practical solutions to weight management in primary careAstbury, Nerys, Morris, Elizabeth 基层医疗中体重管理的实用解决方案 Data suggest that primary care practices could help deliver effective weight management — but only with robust implementation strategies that acknowledge the realities and pressures of primary care settings. 数据表明基层医疗实践可以帮助提供有效的体重管理——但前提是必须有强有力的实施策略，并承认基层医疗环境的现实与压力。 17| Going beyond genomics in precision oncologyPaassen, Irene, Rubin, Mark A. 超越基因组学的精准肿瘤学 A large population-based study from Japan reveals both the promise and the limits of genomic profiling in cancer care, and highlights the need for multidimensional data to guide therapy across diverse populations. 来自日本的一项基于大规模人群的研究揭示了基因组分析在癌症治疗中的前景与局限，并强调需要多维度数据来指导不同人群的治疗。 Research Briefing18| Integration of health check-ups into school and healthcare systems can improve adolescent health in LMICs 将健康检查整合进学校和医疗系统可改善低收入和中等收入国家青少年的健康 In low- and middle-income countries (LMICs), adolescents have limited access to healthcare. A study in urban Zimbabwe demonstrated that routine check-up visits integrated within existing school and healthcare systems are feasible and acceptable. The check-up intervention showed potential for improving health and educational outcomes, as well as the long-term well-being of adolescents. 在低收入和中等收入国家（LMICs），青少年获得医疗服务的机会有限。津巴布韦城市的一项研究表明，将常规健康检查访视整合进现有学校和医疗系统是可行且可接受的。该检查干预显示出改善健康和教育结局以及青少年长期福祉的潜力。 19| PD-1 blockade reprograms antiviral immunity and reduces the HIV reservoir PD-1阻断重编程抗病毒免疫并减少HIV储存库 PD-1 blockade reprograms both innate and adaptive immunity in people living with HIV and cancer, inducing interferon-driven antiviral responses that reduce the HIV reservoir. A pre-existing type I interferon signature predicts reservoir decline, whereas high TGFβ signaling opposes it, defining immune states that influence the outcome of PD-1 therapy. PD-1阻断重编程了HIV感染者和癌症患者的先天与适应性免疫，诱导干扰素驱动的抗病毒应答从而减少HIV储存库。预先存在的I型干扰素特征预测储存库下降，而高TGFβ信号则与之相反，定义了影响PD-1治疗结局的免疫状态。 20| A low-toxicity linezolid analog has potential for use in all patients with tuberculosis 低毒性利奈唑胺类似物具有用于所有结核病患者的潜力 Systematic examination of oxazolidinone analogs for activity against Mycobacterium tuberculosis and limited inhibition of the synthesis of mitochondrial proteins enabled the identification of several compounds with safety suitable for once-daily dosing. The lead molecule is effective in mouse models of disease and safe in four-month toxicity studies. 系统考察了噁唑烷酮类化合物对结核分枝杆菌的活性以及对线粒体蛋白合成的有限抑制作用，从而鉴定了若干安全性适合每日一次给药的化合物。领选分子在小鼠疾病模型中有效，并在为期四个月的毒性研究中显示安全。 21| Capillary blood sampling for detecting biomarkers of Alzheimer’s disease 毛细血管采血用于检测阿尔茨海默病生物标志物 Capillary blood sampling for the Alzheimer’s disease biomarkers p-tau217, NfL and GFAP correlates with venous measures for the same biomarkers. As capillary p-tau217 accurately classified amyloid burden, it might support remote assessment in large-scale epidemiology to estimate the prevalence of Alzheimer’s disease and enable triage into clinical services and trials. 阿尔茨海默病生物标志物p-tau217、NfL和GFAP的毛细血管采血检测与静脉血检测结果相关。由于毛细血管p-tau217能准确分类淀粉样蛋白负荷，它可能支持大规模流行病学中的远程评估，以估计阿尔茨海默病的患病率，并实现向临床服务和试验的分诊。 22| Immune cells in circulation serve as living biomarkers for inflammatory diseases 循环中的免疫细胞作为炎症性疾病的活体生物标志物 Profiling over 6.5 million peripheral blood mononuclear cells from 1,047 patients and 19 diseases at a single-cell transcriptome resolution led to a comprehensive model of inflammation in circulating immune cells. Leveraging this foundational resource enabled us to identify disease-driving inflammatory mechanisms and to build a foundation for a universal diagnostic classification framework. 对来自1,047名患者和19种疾病的超过650万个外周血单核细胞进行单细胞转录组分辨率分析，建立了循环免疫细胞炎症的综合模型。利用这一基础资源，我们得以识别疾病驱动的炎症机制，并为通用的诊断分类框架奠定基础。 23| Large-scale analysis identifies metabolites associated with type 2 diabetes 大规模分析鉴定与2型糖尿病相关的代谢物 An integrated analysis of 23,634 individuals identified 235 circulating metabolites associated with future risk of type 2 diabetes and revealed their potential genetic and environmental determinants. These findings provide a foundation for understanding the metabolic landscape underlying type 2 diabetes risk, informing preventative therapies that target specific metabolic pathways. 对23,634名个体的整合分析鉴定出235种与未来2型糖尿病风险相关的循环代谢物，并揭示了其潜在的遗传和环境决定因素。这些发现为理解2型糖尿病风险的代谢图景奠定了基础，可指导针对特定代谢通路的预防性治疗。 24| Clinically relevant variants from the Mexican biobank show striking diversity across Hispanic people 墨西哥生物库中临床相关变异在西班牙裔人群中显示出惊人多样性 Ancestry-aware genomic analyses of 6,011 people from the Mexican Biobank characterized allele frequency variation in 42,769 clinically relevant variants across Mexico, accounting for local ancestry and fine-scale geography. Results are accessible through a web-based application, MexVar, to enable data exploration and to foster biomedical research in Hispanic populations. 对墨西哥生物库中6,011人的祖先感知基因组分析，表征了墨西哥各地42,769个临床相关变异的等位基因频率变化，考虑了当地祖先和精细地理尺度。结果通过基于网络的应用MexVar公开，以促进数据探索和西班牙裔人群的生物医学研究。 25| Blood biomarkers reveal pathways associated with multimorbidity 血液生物标志物揭示与多重疾病相关的通路 Several biological processes contribute to the development of specific combinations of chronic diseases (disease patterns) and the progression of multimorbidity over time. We find that metabolic disturbances have a central role in multimorbidity, representing a potential target for interventions to mitigate multimorbidity burden among older adults. 多种生物过程促成了特定慢性病组合（疾病模式）的发生以及多重疾病随时间进展。我们发现代谢紊乱在多重疾病中起核心作用，代表了减轻老年人多重疾病负担的潜在干预靶点。 Perspective26| Scaling medical AI across clinical contextsLi, Michelle M., Reis, Ben Y., Rodman, Adam, et al. 医疗人工智能跨临床场景的扩展 To function safely and effectively, medical AI models must adapt automatically to differences in users, health systems, geographies, diseases and populations. This Perspective proposes context switching as the defining paradigm of medical AI, outlining early strategies and opportunities for development. 为了安全有效地发挥作用，医疗AI模型必须自动适应用户、卫生系统、地理位置、疾病和人群的差异。本视角提出上下文切换作为医疗AI的定义范式，并概述了早期策略与发展机遇。 Review Article27| The science of psychedelic medicineSiegel, Joshua S., Liston, Conor, Nicol, Ginger E., et al. 迷幻药物医学的科学 This Review outlines the science behind psychedelic medicine and integrates mechanistic knowledge with clinical evidence across neuropsychiatric indications, highlighting challenges, controversies and opportunities. 本综述概述了迷幻药物医学背后的科学，将机制知识与神经精神病学适应症的临床证据相整合，突出了挑战、争议与机遇。 Matters Arising28| Concerns over conclusions in an ultra-processed food trialLudwig, David S., Willett, Walter C., Putt, Mary E. 对超加工食品试验结论的担忧 [No short summary] [无短摘要] 29| Concerns around evidence that food processing should be included in dietary guidanceRobinson, Eric, Forde, Ciarán G. 关于应将食品加工纳入膳食指导证据的担忧 [No short summary] [无短摘要] 30| Concerns about attributing weight change to processing in a crossover feeding trialWang, Zixuan, Peng, Can 关于交叉喂养试验中将体重变化归因于加工的担忧 [No short summary] [无短摘要] 31| Reply to Ludwig, D. S. et al.; Robinson, E. & Forde, C. G.; Wang, Z. & Peng, C.Dicken, Samuel J., Brown, Adrian, Batterham, Rachel L. 对Ludwig, D. S.等人；Robinson, E. & Forde, C. G.；Wang, Z. & Peng, C.的回复 [No short summary] [无短摘要] Brief Communication32| Contaminating plasmid sequences and disrupted vector genomes in the liver following adeno-associated virus gene therapyBuddle, Sarah, Brown, Li-An K., Morfopoulou, Sofia, et al. 腺相关病毒基因治疗后肝脏中污染的质粒序列和受破坏的载体基因组 Analyses of liver biopsies from a child with spinal muscular atrophy treated with adeno-associated virus gene therapy who developed hepatitis reveal contaminating manufacturing plasmids and disrupted vector genomes, possibly resulting from recombination events. 对一名接受腺相关病毒基因治疗并发生肝炎的脊髓性肌萎缩症患儿肝活检的分析显示，存在污染的生产用质粒和受破坏的载体基因组，可能由重组事件引起。 Article33| Intrathecal onasemnogene abeparvovec in treatment-naive patients with spinal muscular atrophy: a phase 3, randomized controlled trialProud, Crystal M., Vũ, Dũng Chí, Wilmshurst, Jo M., et al. 治疗初治脊髓性肌萎缩症患者的鞘内注射onasemnogene abeparvovec：一项3期随机对照试验 The phase 3 STEER trial showed that a single intrathecal dose of onasemnogene abeparvovec significantly improved motor function in children and adolescents with spinal muscular atrophy versus sham, with a similar and acceptable safety profile. 3期STEER试验显示，单次鞘内注射onasemnogene abeparvovec显著改善了脊髓性肌萎缩症儿童和青少年的运动功能，与假手术相比安全性相似且可接受。 继续输出第4部分 34| Intrathecal onasemnogene abeparvovec for treatment-experienced patients with spinal muscular atrophy: a phase 3b, open-label trialKwon, Jennifer M., Munell, Francina, Le Goff, Laure, et al. 治疗经验脊髓性肌萎缩症患者的鞘内onasemnogene abeparvovec：一项3b期开放标签试验 Results of the phase 3b STRENGTH study show that intrathecal onasemnogene abeparvovec has a favorable safety profile consistent with findings in treatment-naïve patients and may be another treatment option for patients with spinal muscular atrophy. 3b期STRENGTH研究结果显示，鞘内onasemnogene abeparvovec具有与初治患者一致的有利安全性特征，并可能成为脊髓性肌萎缩症患者的另一种治疗选择。 35| Implementation and evaluation of the Y-Check comprehensive adolescent health check-up intervention in Zimbabwe: a pre−post mixed-methods studyDoyle, Aoife M., Nzvere, Farirai, Manyau, Salome, et al. 津巴布韦Y-Check青少年综合健康检查干预的实施与评估：一项前后混合方法研究 A WHO-supported pre−post study shows that implementation of the Y-Check comprehensive health check program is feasible and acceptable for adolescents in Zimbabwe, offering screening for 25 health conditions and behaviors, health promotion, on-site care and referral. 一项得到世卫组织支持的前后研究表明，在津巴布韦对青少年实施Y-Check综合健康检查计划是可行且可接受的，该计划提供25种健康状况和行为的筛查、健康促进、现场护理和转诊。 36| Innate antiviral and immune functions associated with the HIV reservoir decay after anti-PD-1 therapyTalla, Aarthi, Azevedo, Joao L. L. C., Latif, Muhammad Bilal, et al. 抗PD-1治疗后HIV储存库衰减相关的先天抗病毒和免疫功能 A follow-up analysis of a clinical trial that evaluated anti-PD-1 therapy in patients with cancer who are living with HIV provides mechanistic insights into transcriptomic, cellular and cytokine changes related to immune checkpoint inhibitor treatment and identifies a signature associated with clinical response. 对一项在同时患癌和HIV的患者中评估抗PD-1治疗的临床试验的后续分析，提供了与免疫检查点抑制剂治疗相关的转录组、细胞和细胞因子变化的机制洞见，并鉴定出与临床应答相关的特征。 37| Housing modifications for heat adaptation, thermal comfort and malaria vector control in rural African settlementsAbong’o, Bernard, Kwaro, Daniel, Bange, Teresa, et al. 非洲农村聚落中用于热适应、热舒适和疟疾媒介控制的住房改造 A randomized field study in rural western Kenya, a region most vulnerable to the health impacts of climate change, found that modifying houses with cool-roofs and vector proofing most effectively reduced indoor heat, improved thermal comfort and lowered malaria mosquito density. 在气候变化健康影响最脆弱的肯尼亚西部农村地区进行的一项随机现场研究发现，使用凉爽屋顶和防媒介改造房屋最有效地降低了室内热量，提高了热舒适度，并降低了疟疾蚊虫密度。 38| Global burden of amphetamine, cannabis, cocaine and opioid use in 204 countries, 1990–2023: a Global Burden of Disease StudyKang, Jiseung, Kim, Hyeon Jin, Kim, Min Seo, et al. 1990–2023年204个国家安非他命、大麻、可卡因和阿片类药物使用的全球负担：全球疾病负担研究 Global Burden of Disease estimates show that between 1990 and 2023, the prevalence and burden of drug use disorders, inclusive of amphetamine, cannabis, cocaine and opioid use, have been increasing in high-income countries, particularly in the USA. 全球疾病负担估计显示，1990年至2023年间，包括安非他命、大麻、可卡因和阿片类药物使用的药物使用障碍的患病率和负担在高收入国家（尤其是美国）持续增加。 39| Estimating the number of incorrect tuberculosis diagnoses in low- and middle-income countriesvan Lieshout Titan, Ana, Dodd, Peter J., Cohen, Ted, et al. 估计低收入和中等收入国家中结核病错误诊断的数量 A Bayesian analysis of diagnostic data reported to the World Health Organization reveals that approximately 2 million people were incorrectly diagnosed with tuberculosis (received a false-positive result) and 1 million received a false-negative result, emphasizing the critical need for higher-sensitivity bacteriological tests in the future. 对报告给世界卫生组织的诊断数据的贝叶斯分析显示，约200万人被错误诊断为结核病（假阳性），100万人获得假阴性结果，强调未来需要更高灵敏度细菌学检测的迫切性。 40| Discovery and development of a new oxazolidinone with reduced toxicity for the treatment of tuberculosisCrowley, Brendan M., Boshoff, Helena I., Boving, Aidan, et al. 用于治疗结核病的低毒性新型噁唑烷酮的发现与开发 MK-7762 is a new oxazolidinone antitubercular agent that is structurally similar to linezolid, and demonstrated in vivo efficacy, lesion penetration and limited toxicity compared to linezolid, indicating it could be used in broad tuberculosis regimens. MK-7762是一种新型噁唑烷酮抗结核药物，结构上类似于利奈唑胺，与利奈唑胺相比显示出体内疗效、病灶渗透性和有限毒性，表明它可用于广泛的结核病治疗方案。 41| Live-attenuated chikungunya vaccine in children: a randomized phase 2 trialWeisová, Petronela, Scheiblauer, Susanne, Ecker, Jacqueline, et al. 儿童中减毒活疫苗预防基孔肯雅热：一项随机2期试验 In a phase 2 randomized, controlled, dose–response trial, the live-attenuated chikungunya vaccine (VLA1553) was given in full and half doses to children under the age of 12 in Honduras and the Dominican Republic and was found to be safe and immunogenic, with the results supporting selection of the full-dose VLA1553 in future clinical trials in this population. 在一项2期随机、对照、剂量-反应试验中，向洪都拉斯和多米尼加共和国12岁以下儿童给予全剂量和半剂量的减毒活基孔肯雅疫苗（VLA1553），结果显示其安全且具有免疫原性，支持在该人群未来临床试验中选择全剂量VLA1553。 42| Upregulation of reward mesolimbic activity and immune response to vaccination: a randomized controlled trialLubianiker, Nitzan, Koren, Tamar, Djerasi, Meshi, et al. 奖励中脑边缘系统活动上调与疫苗免疫应答：一项随机对照试验 Upregulation of the ventral tegmental area via neurofeedback is associated with a stronger immune response to hepatitis B virus vaccination, and VTA upregulation is achieved through conscious positive expectations. 通过神经反馈上调腹侧被盖区与对乙型肝炎病毒疫苗的更强免疫应答相关，而VTA上调通过有意识的积极期望实现。 43| External trigeminal nerve stimulation in youth with ADHD: a randomized, sham-controlled, phase 2b trialConti, Aldo Alberto, Bozhilova, Natali, Eraydin, Irem Ece, et al. 青少年ADHD中外部三叉神经刺激：一项随机、假刺激对照的2b期试验 A large, multicenter, double-blind RCT in 150 children and adolescents found that external trigeminal nerve stimulation, although safe and well tolerated, did not produce significant short-term or long-term clinical benefits for ADHD compared to sham treatment. 一项涉及150名儿童和青少年的大型、多中心、双盲随机对照试验发现，尽管外部三叉神经刺激安全且耐受性良好，但与假刺激相比并未产生对ADHD显著的短期或长期临床益处。 44| A short-acting psychedelic intervention for major depressive disorder: a phase IIa randomized placebo-controlled trialErritzoe, David, Barba, Tommaso, Benway, Tiffanie, et al. 用于重度抑郁障碍的短效迷幻干预：一项IIa期随机安慰剂对照试验 A single intravenous dose of the psychedelic dimethyltryptamine, combined with psychological support, produces rapid and lasting reductions in depressive symptoms in adults with major depressive disorder. 单次静脉给予迷幻药二甲基色胺并结合心理支持，在重度抑郁障碍成人中产生快速且持久的抑郁症状减轻。 45| A minimally invasive dried blood spot biomarker test for the detection of Alzheimer’s disease pathologyHuber, Hanna, Montoliu-Gaya, Laia, Brum, Wagner S., et al. 用于检测阿尔茨海默病病理的微创干血斑生物标志物检测 This multicenter study demonstrates use of dried and capillary blood as a minimally invasive, scalable approach for Alzheimer’s biomarker testing in research, with potential as a widely scalable population-based research approach, especially in resource-limited settings. 这项多中心研究展示了使用干血和毛细血管血作为阿尔茨海默病生物标志物检测的微创、可扩展研究方法，具有作为广泛可扩展的基于人群的研究途径的潜力，尤其在资源有限的环境中。 46| Reliability of LLMs as medical assistants for the general public: a randomized preregistered studyBean, Andrew M., Payne, Rebecca Elizabeth, Parsons, Guy, et al. 大型语言模型作为面向公众的医疗助手的可靠性：一项随机预注册研究 In a randomized controlled study involving 1,298 participants from a general sample, performance of humans when assisted by a large language model (LLM) was sensibly inferior to that of the LLM alone when assessing ten medical scenarios leading to disease identification and recommendations for treatment. 一项涉及1,298名普通样本参与者的随机对照研究显示，在评估十个导致疾病识别和治疗推荐的医疗场景时，由大型语言模型（LLM）辅助的人类表现明显劣于LLM单独表现。 47| A large language model for complex cardiology careO’Sullivan, Jack W., Palepu, Anil, Saab, Khaled, et al. 用于复杂心脏病护理的大型语言模型 In a randomized study involving 9 general cardiologists and 107 real-world patient cases, assistance from a specifically tailored large language model resulted in preferable responses on complex case management compared to physicians alone, as rated by specialist cardiologists using a multidimensional scoring rubric. 一项涉及9名普通心脏病学家和107个真实世界患者病例的随机研究显示，由专门定制的大型语言模型辅助，在复杂病例管理上的回应优于单独医师的表现，由专科心脏病学家使用多维度评分量表评定。 48| Anti-inflammatory therapy with low-dose IL-2 in acute coronary syndromes: a randomized phase 2 trialSriranjan-Rothwell, Rouchelle S., Zhao, Tian X., Hoole, Stephen P., et al. 低剂量IL-2抗炎治疗用于急性冠脉综合征：一项随机2期试验 In a randomized phase 2 trial in patients with acute coronary syndrome and high levels of the inflammation biomarker C-reactive protein, treatment with low-dose interleukin-2 increased the numbers of regulatory T cells and reduced arterial inflammation, compared to placebo. 在一项针对急性冠脉综合征且炎症标志物C反应蛋白水平高的患者的随机2期试验中，与安慰剂相比，低剂量白介素-2治疗增加了调节性T细胞数量并降低了动脉炎症。 49| Interpretable inflammation landscape of circulating immune cellsJiménez-Gracia, Laura, Maspero, Davide, Aguilar-Fernández, Sergio, et al. 循环免疫细胞的可解释炎症图景 Including data from 1,047 patients across 19 inflammatory diseases, a new atlas presents a comprehensive model of inflammation in circulating immune cells. 纳入来自19种炎症性疾病的1,047名患者的数据，一份新图谱呈现了循环免疫细胞炎症的综合模型。 50| Implementation and effectiveness of a care process to prioritize weight management in primary care: a stepped-wedge cluster-randomized trialPerreault, Leigh, Pan, Qing, Rodriguez, Carlos, et al. 在基层医疗中优先体重管理的护理流程的实施与有效性：一项阶梯式整群随机试验 A pragmatic study across 56 clinics in the US state of Colorado shows that a complex multifaceted intervention in primary care clinics can improve patient weight outcomes compared with usual care. 在美国科罗拉多州56家诊所进行的一项实用性研究显示，基层医疗诊所中复杂的多方面干预与常规护理相比可改善患者体重结局。 51| Tirzepatide on obstructive sleep apnea-related cardiometabolic risk: secondary outcomes of the SURMOUNT-OSA randomized trialMalhotra, Atul, Grunstein, Ronald, Azarbarzin, Ali, et al. 替尔泊肽对阻塞性睡眠呼吸暂停相关心代谢风险的影响：SURMOUNT-OSA随机试验的次要结局 In a prespecified secondary analysis of the SURMOUNT-OSA trial, tirzepatide improved cardiometabolic outcomes in patients with moderate-to-severe obstructive sleep apnea and obesity. 在SURMOUNT-OSA试验的预先指定的次要分析中，替尔泊肽改善了中重度阻塞性睡眠呼吸暂停合并肥胖患者的心代谢结局。 52| Circulating metabolites, genetics and lifestyle factors in relation to future risk of type 2 diabetesLi, Jun, Hu, Jie, Yun, Huan, et al. 循环代谢物、遗传和生活方式因素与未来2型糖尿病风险的关系 Researchers studied the blood-based metabolome of over 23,000 people from ten ethnically diverse cohorts. They identified 235 metabolites associated with future risk of type 2 diabetes (T2D). By integrating genetic and modifiable lifestyle factors, their findings provide insights into T2D mechanisms and could improve risk prediction and inform precision prevention. 研究人员研究了来自十个种族多样性队列的超过23,000人的基于血液的代谢组。他们鉴定出235种与未来2型糖尿病（T2D）风险相关的代谢物。通过整合遗传和可改变的生活方式因素，他们的发现提供了对T2D机制的洞见，并可能改善风险预测和指导精准预防。 53| Soluble MAdCAM-1 as a biomarker in metastatic renal cell carcinomaAlves Costa Silva, Carolina, Machaalani, Marc, Saliby, Renee Maria, et al. 可溶性MAdCAM-1作为转移性肾细胞癌的生物标志物 A clinical cohort-based biomarker study in patients with metastatic renal cell carcinoma demonstrates that blood levels of soluble mucosal addressin cell adhesion molecule-1 are prognostic for survival in patients treated with tyrosine kinase inhibitors and immune checkpoint inhibitors and may serve as a surrogate marker for gut dysbiosis based on integrated data from three clinical trials. 一项基于转移性肾细胞癌患者临床队列的生物标志物研究表明，可溶性黏膜地址素细胞黏附分子-1的血液水平对接受酪氨酸激酶抑制剂和免疫检查点抑制剂治疗的患者的生存具有预后价值，并可能作为基于三项临床试验整合数据的肠道菌群失调的替代标志物。 54| Repotrectinib in NTRK fusion–positive advanced solid tumors: a phase 1/2 trialBesse, Benjamin, Lin, Jessica J., Bazhenova, Lyudmila, et al. Repotrectinib治疗NTRK融合阳性晚期实体瘤：一项1/2期试验 In the phase 1/2 TRIDENT-1 trial, treatment of patients with NTRK fusion–positive advanced solid tumors with the tyrosine kinase inhibitor repotrectinib—selective for ROS1, TRKA−C and ALK—was safe and resulted in durable systemic and intracranial clinical response. 在1/2期TRIDENT-1试验中，使用选择性针对ROS1、TRKA−C和ALK的酪氨酸激酶抑制剂repotrectinib治疗NTRK融合阳性晚期实体瘤患者是安全的，并产生了持久的系统性和颅内临床应答。 55| Real-world clinical utility of comprehensive genomic profiling in advanced solid tumorsSaito, Yuki, Horie, Sara, Kogure, Yasunori, et al. 综合基因组分析在晚期实体瘤中的真实世界临床效用 Analyses of real-world genomic and clinical data from 54,185 patients with solid cancer receiving care within the Japanese healthcare system reveal the clinical utility of genomic sequencing and highlight differences across 81 tumor types. 对日本医疗体系内54,185名接受治疗的实体癌患者的真实世界基因组和临床数据的分析，揭示了基因组测序的临床效用，并突出了81种肿瘤类型之间的差异。 （继续输出第8部分） 继续输出第8部分 56| CD4+ T cells mediate CAR-T cell-associated immune-related adverse events after BCMA CAR-T cell therapyHo, Matthew, Paruzzo, Luca, Noll, Julia Han, et al. CD4+ T细胞介导BCMA CAR-T细胞治疗后的CAR-T细胞相关免疫相关不良事件 An in-depth analysis of tissue biopsies from patients with multiple myeloma and CAR T cell therapy-associated immune-related adverse events (CirAEs) after treatment with commercial BCMA-targeted CAR T cell therapy shows that CD4+ CAR T cells mediate off-tumor toxicities and that high CD4:CD8 ratio at apheresis, robust early CAR T cell expansion, ICANS and ciltacabtagene autoleucel treatment are independently associated with the development of CirAEs. 对使用商业BCMA靶向CAR T细胞治疗的多发性骨髓瘤患者及治疗后出现CAR T细胞相关免疫相关不良事件（CirAEs）的组织活检的深入分析显示，CD4+ CAR T细胞介导了脱靶毒性，且采集时高CD4:CD8比率、早期CAR T细胞强劲扩增、ICANS以及ciltacabtagene autoleucel治疗独立与CirAEs的发生相关。 57| Abemaciclib in meningiomas with somatic NF2 or CDK pathway alterations: the phase 2 Alliance A071401 trialBrastianos, Priscilla K., Dooley, Katharine, Geyer, Susan, et al. Abemaciclib治疗体细胞NF2或CDK通路改变的脑膜瘤：2期Alliance A071401试验 In an arm of an ongoing multicenter phase 2 trial testing different therapies in patients with genetically profiled grade 2 or 3 meningiomas, treatment with an oral CDK4/6 inhibitor met the primary endpoint for progression-free survival at 6 months in patients with CDK or NF2 alterations. 在一项正在进行的、针对基因剖析的2级或3级脑膜瘤患者测试不同疗法的多中心2期试验的一个分支中，口服CDK4/6抑制剂治疗在具有CDK或NF2改变的患者中达到了6个月无进展生存的主要终点。 58| Clinical genetic variation across Hispanic populations in the Mexican BiobankBarberena-Jonas, Carmina, Medina-Muñoz, Santiago G., Cedillo-Castelán, Viankail, et al. 墨西哥生物库中西班牙裔人群的临床遗传变异 Analyzing data of the Mexican Biobank project, a new study finds regional differences in clinically relevant genetic frequencies and presents MexVar, a publicly accessible resource designed to support ancestry-informed genetic testing. 分析墨西哥生物库项目数据的一项新研究发现了临床相关遗传频率的区域差异，并推出了MexVar这一公开资源，旨在支持基于祖先信息的遗传检测。 59| Shared and specific blood biomarkers for multimorbidityOrnago, Alice Margherita, Gregorio, Caterina, Triolo, Federico, et al. 多重疾病的共享与特异性血液生物标志物 Growth differentiation factor 15, hemoglobin A1c, cystatin C, leptin and insulin levels were consistently and positively associated with measures of multimorbidity, both cross-sectional and longitudinal, in individuals aged 60 and over. 生长分化因子15、糖化血红蛋白、胱抑素C、瘦素和胰岛素水平在60岁及以上个体中，与多重疾病的横断面和纵向测量指标持续呈正相关。 60| Eliminating opioid prescriptions from outpatient minimally invasive gynecologic surgery: a randomized trialZakhari, Andrew, Désilets, Jade, Della Rocca, Cassandra, et al. 从门诊微创妇科手术中消除阿片类处方：一项随机试验 A randomized controlled trial found that eliminating opioids after minimally invasive gynecologic surgery did not compromise pain control at postoperative day 1, with similar pain scores and recovery outcomes between opioid-free and restrictive opioid groups up to day 7. 一项随机对照试验发现，微创妇科手术后消除阿片类药物并未损害术后第1天的疼痛控制，在无阿片类组与限制性阿片类组之间，直至第7天的疼痛评分和恢复结局相似。 61| A multimodal sleep foundation model for disease predictionThapa, Rahul, Kjaer, Magnus Ruud, He, Bryan, et al. 用于疾病预测的多模态睡眠基础模型 A deep learning-based model, developed using the rich, multimodal data available from polysomnography-derived sleep recordings, performs well on common sleep analysis tasks and predicts future disease risk across a range of diseases. 基于深度学习、利用多导睡眠图衍生的丰富多模态睡眠记录数据开发的模型，在常见睡眠分析任务上表现良好，并可预测多种疾病的未来风险。 📖下期再见 敬请期待下一期《顶刊课读》前沿追踪，感谢你的一路陪伴。 ——坐看云起时，静待花开日。 本《顶刊课读》中的顶刊范围包括Science及子刊和Nature及子刊和PNAS等16本顶刊： #Nature; #Sicence; #PNAS; #Science Advances; #Nature Cliamate Change; #Nature Machine Intelligence; #Nature Human Behaviour; #Nature Sustainability; #Nature Reviews Earth & Environment; #Nature Geoscience; #Nature Cities; #Nature Computional Science; #Nature Ecology & Evolution; #Nature Health; #Nature Mental Health; #Nature Medicine #Narue Water; #Nature Food; #顶刊前沿 #前沿方向 #前沿追踪 #科学问题 #未来研究方向