来自杂志 Nature Medicine 的文献。
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1.
孤舟蓑笠翁
(2025-06-19 20:37):
#paper 【doi】10.1038/s41591-025-03563-4;【发表年份】2025年;【期刊】Nature Medicine;【标题】Social disadvantage accelerates aging。【内容总结】这项研究的目标是调查社会劣势(比如低教育水平或贫困)是否会加速人体衰老过程,他们用了四个大型人群队列的数据(包括UK Biobank、芬兰公共部门研究等),测量了参与者的社会劣势指标(如教育和成人社会经济地位),并分析血浆蛋白质(用SomaScan平台检测了7000多种蛋白)和83种年龄相关疾病(如糖尿病、心脏病)的关系,主要方法包括队列研究设计、时间事件分析(Cox比例风险模型评估疾病风险)、中介分析(量化蛋白质的介导效应)和GO通路富集分析。简单来说,他们发现社会劣势的人更容易得66种衰老相关疾病(风险增加1.2-1.5倍),14种特定蛋白质(如S100A12、CRP和DNAJB9)部分介导了这一关联(最高达39%),这些蛋白质激活了NF-kB和IL-8炎症通路,表明社会劣势通过加速免疫衰老来促进疾病发生。
Nature Medicine,
2025-5.
DOI: 10.1038/s41591-025-03563-4
Abstract:
Abstract Social disadvantage, like advanced age, is a risk factor for a broad range of health conditions; however, whether it influences the aging process remains unclear. Here, using a multicohort …
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Abstract Social disadvantage, like advanced age, is a risk factor for a broad range of health conditions; however, whether it influences the aging process remains unclear. Here, using a multicohort approach, we investigated the associations of social disadvantage with age-related plasma proteins and age-related diseases. We found proteomic signatures of accelerated immune aging and 14 specific age-related proteins linked to social disadvantage during both early and later life. Individuals experiencing social disadvantage had an increased risk of 66 age-related diseases, with up to 39% of these associations mediated by the 14 age-related proteins (for example, DNAJB9, F2, HSPA1A, BGN). The main enriched pathway involved the upregulation of the pro-inflammatory regulator NF-κB24 and its downstream factor interleukin-8. Our findings support the hypothesis that social disadvantage throughout the life course may accelerate aging, a biological mechanism that could explain why social stratification plays such a fundamental role in determining human health.
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2.
孤舟蓑笠翁
(2025-06-17 22:27):
#paper 【doi】10.1038/s41591-025-03592-z;【发表年份】2025;【期刊】Nature Medicine;【标题】Single-cell profiling of the human endometrium in polycystic ovary syndrome。【内容总结】通俗地说,这项研究想搞清楚为什么患有多囊卵巢综合征(PCOS)的女性子宫内膜容易出问题(比如着床失败、流产风险高),以及药物二甲双胍是否有效。他们用了先进的单细胞测序技术,详细分析了27名超重/肥胖且有胰岛素抵抗的PCOS女性和对照组女性的子宫内膜细胞组成和基因活动,并在部分PCOS女性用药(二甲双胍或生活方式干预)16周后再次分析。具体来说,研究发现PCOS女性的子宫内膜里上皮细胞变多了,而间质和免疫细胞变少了,并且许多控制细胞粘附、细胞外基质和整合素信号的关键基因(如ITGA2, ITGA3)在特定的上皮细胞亚群(如SOX9+LGR5+、AR+细胞)中变得不正常,这些异常与子宫内膜癌和着床失败有关。重要的是,用二甲双胍治疗16周后,这些异常的基因表达在多个关键细胞类型中(特别是上皮细胞和免疫细胞)得到了明显的改善,甚至部分恢复了,而生活方式干预效果相对较弱。这揭示了PCOS子宫内膜在细胞层面上的具体变化机制,并表明二甲双胍能通过调节这些细胞特异性的异常来帮助恢复子宫内膜健康。
Nature Medicine,
2025-6.
DOI: 10.1038/s41591-025-03592-z
Abstract:
Abstract Polycystic ovary syndrome (PCOS) has a negative effect on the receptivity of the endometrium to embryo implantation and increases the risk of miscarriage and endometrial cancer. The cellular and …
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Abstract Polycystic ovary syndrome (PCOS) has a negative effect on the receptivity of the endometrium to embryo implantation and increases the risk of miscarriage and endometrial cancer. The cellular and molecular heterogeneity of the endometrium in women with PCOS has not been well studied. Our study presents a comprehensive cellular atlas of the endometrium during the proliferative phase in women with PCOS characterized by overweight and obesity, hyperandrogenism and insulin resistance compared with controls of similar age, weight and body mass index. Analysis of 247,791 isolated endometrial nuclei from 27 biopsies (5 controls and 12 PCOS cases at baseline and 7 after 16 weeks of metformin and 3 after lifestyle intervention) revealed cell-type-specific disease signatures and variations in cellular composition and localization. Samples taken after 16 weeks of metformin treatment and lifestyle management showed extensive recovery of disease-specific endometrial signatures. We linked the specific role of each cell type to clinical features such as hyperandrogenism and insulin resistance, and specific cell types to risk of endometrial and metabolic disease. In addition, potential therapeutic targets such as integrin inhibitors were identified and the role of metformin in restoring endometrial health in patients with PCOS was highlighted. Our findings lay the groundwork to significantly advance the understanding of PCOS-specific endometrial dysfunction for future targeted therapies.
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3.
孤舟蓑笠翁
(2025-06-16 22:13):
#paper 【doi】10.1038/s41591-025-03653-3;【发表年份】2025年;【期刊】Nature Medicine;【标题】Effect of felzartamab on the molecular phenotype of antibody-mediated rejection in kidney transplant biopsies。【内容总结】本研究目标是探索新药felzartamab如何改善肾移植后常见问题——抗体排斥反应(ABMR)的分子变化,通过一项小规模临床试验:20名患者被分成两组(10人用felzartamab,10人用安慰剂),研究者用基因检测工具分析他们肾活检样本在治疗前、24周(治疗结束)和52周(停药后)的数据,结果发现,felzartamab在治疗期间有效降低了排斥相关基因(如干扰素诱导基因和自然杀伤细胞基因)的表达,平均减少47%和28%,但停药后8成患者反弹;同时,药物意外减轻了肾组织损伤标志物(如IRRAT30和IRITD3等)的长期表达,且未引发有害的T细胞反应,表明短期治疗虽不能完全阻止排斥复发,但可能保护肾脏功能。
Nature Medicine,
2025-5.
DOI: 10.1038/s41591-025-03653-3
Abstract:
Abstract A recent randomized controlled trial demonstrated that treatment with anti-CD38 monoclonal antibody felzartamab suppressed antibody-mediated rejection (ABMR) in kidney transplant patients but with recurrence after treatment in some patients. …
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Abstract A recent randomized controlled trial demonstrated that treatment with anti-CD38 monoclonal antibody felzartamab suppressed antibody-mediated rejection (ABMR) in kidney transplant patients but with recurrence after treatment in some patients. Here we examined the molecular effects of 6 months of felzartamab treatment on biopsies from the trial using genome-wide microarray analysis, comparing pretreatment, end-of-treatment (week 24) and posttreatment (week 52) biopsies from ten patients treated with felzartamab and ten patients in the placebo group. Felzartamab reduced molecular ABMR activity scores in all nine patients with baseline ABMR activity, selectively suppressing interferon gamma-inducible and natural killer cell transcripts, with minimal effect on ABMR stage-related endothelial transcripts. Suppression was often incomplete when ABMR activity was intense, and molecular recurrence was nearly universal by week 52. However, we also found that felzartamab had parenchymal benefits at week 52, slowing the trajectories of molecular injury scores beyond the treatment period, suggesting that suppression of ABMR activity could potentially slow future progression to kidney failure. These data provide preliminary molecular insights into the effects of CD38-directed treatment for ABMR, which have the potential to inform future therapeutic strategies.
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4.
孤舟蓑笠翁
(2025-06-16 21:14):
#paper 【doi】10.1038/s41591-025-03570-5;【发表年份】2025年;【期刊】Nature Medicine;【标题】Optimal dietary patterns for healthy aging。【内容总结】这项研究的目标是找出能最好促进健康老龄化的饮食模式,因为全球人口老龄化加剧,许多人面临慢性病和功能衰退的风险,而饮食是预防疾病和维持生活质量的关键因素。简单来说,研究者使用了美国两大长期队列研究的数据——护士健康研究和健康专业人员随访研究,从1986年到2016年追踪了105,015名参与者,分析了八种健康饮食模式(如替代健康饮食指数AHEI、地中海饮食aMED、DASH饮食等)和超加工食品摄入与健康老龄化的关系;健康老龄化定义为活到70岁时无11种主要慢性病、认知功能完好、身体功能正常和心理健康良好。具体地,结果显示,坚持这些健康饮食模式的人有显著更高的健康老龄化几率,其中AHEI饮食效果最强(最高依从组比最低组的几率高出86%),而超加工食品则会降低几率;食物方面,多吃水果、蔬菜、全谷物、坚果、豆类和低脂乳制品有益,但反式脂肪、钠、含糖饮料和红肉或加工肉有害,这些发现在男女中都成立,尤其对女性、吸烟者和体重较高者更明显。
5.
孤舟蓑笠翁
(2025-06-15 09:44):
#paper 【doi】10.1038/s41591-025-03562-5;【发表年份】2025年;【期刊】Nature Medicine;【标题】Prospective, multicenter validation of a platform for rapid molecular profiling of central nervous system tumors。【内容总结】研究人员想开发一个又快又准的方法来诊断脑肿瘤,因为现有技术太慢太贵,尤其在全球资源有限的地方不好用,所以他们搞了个叫Rapid-CNS2的新工具,结合纳米孔测序和自适应采样技术,能在手术中30分钟内给出肿瘤的大致分类和基因拷贝数信息,24小时内提供完整的分子报告,包括突变、融合和甲基化数据,还搭配了一个叫MNP-Flex的智能分类器处理甲基化信息;他们在多个医院测试了301个肿瘤样本,结果超级好——甲基化家族分类准确率92.9%,基因突变检测与常规方法91.67%一致,拷贝数分析与金标准完全匹配,MNP-Flex更牛,家族和子类准确率分别达99.6%和99.2%,术中测试15分钟就搞定83%的样本,整体诊断时间从几周缩到40小时,让医生能更快制定个性化治疗方案。
6.
孤舟蓑笠翁
(2025-06-13 20:26):
#paper 【doi】10.1038/s41591-025-03692-w;【发表年份】2025年;【期刊】Nature Medicine;【标题】T and B cell responses against Epstein-Barr virus in primary sclerosing cholangitis。该研究简略地探讨了EB病毒(EBV)与原发性硬化性胆管炎(PSC)的免疫关联,发现PSC患者的T/B细胞对EBV反应异常增强。具体通过比较504名PSC患者和904名健康人的T细胞受体(TCR)测序,鉴定出1008个PSC相关克隆型,其中多数靶向EBV抗原(如BZLF1和EBNA3),且受PSC风险HLA等位基因(如HLA-B*08:01)限制;通过噬菌体免疫沉淀测序(PhIP-seq)分析120名PSC和202名健康人血清,显示PSC患者抗EBV抗体反应显著升高(尤其靶向BMRF1等裂解期蛋白);从PSC肝脏浸润B细胞提取的单克隆抗体也证实靶向EBV抗原(如BFRF3);最后通过超116万人电子病历分析,发现传染性单核细胞增多症(EBV引起)患者患PSC风险比健康人高12倍(95% CI: 6.3-22.9),远高于其他免疫疾病(如克罗恩病),表明EBV感染与PSC发病存在强流行病学关联,提示EBV再激活可能在PSC病理中起关键作用。
Nature Medicine,
2025-6-11.
DOI: 10.1038/s41591-025-03692-w
Abstract:
Abstract Primary sclerosing cholangitis (PSC) is an idiopathic, progressive and incurable liver disease. Here, we aimed for systematic analyses of adaptive immune responses in PSC. By profiling the T cell …
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Abstract Primary sclerosing cholangitis (PSC) is an idiopathic, progressive and incurable liver disease. Here, we aimed for systematic analyses of adaptive immune responses in PSC. By profiling the T cell repertoires of 504 individuals with PSC and 904 healthy controls, we identified 1,008 clonotypes associated with PSC. A substantial fraction of these clonotypes was restricted to known PSC human leukocyte antigen susceptibility alleles and known to target Epstein–Barr virus (EBV) epitopes. We further utilized phage-immunoprecipitation sequencing to determine antibody epitope repertoires of 120 individuals with PSC and 202 healthy controls, which showed a higher burden of anti-EBV responses in PSC than controls. EBV-specific monoclonal antibodies isolated from B cells in PSC livers corroborated convergent B and T cell responses against EBV. By analyzing electronic health records of >116 million people, we identified an association between infectious mononucleosis and PSC (odds ratio, 12; 95% confidence interval, 6.3–22.9), suggesting a link between EBV and PSC.
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7.
薛定谔的猫
(2025-02-28 22:53):
#paper DOI: 10.1038/s41591-025-03517-w
Artificial intelligence for individualized treatment of persistent atrial fibrillation: a randomized controlled trial。心房颤动是最常见的心律失常之一,传统上基于解剖的心脏射频消融术有复发率高的缺点。TAILORED-AF是一项多中心RCT研究,旨在比较传统肺静脉隔离(PVI)与PVI基础上联合人工智能(基于一种识别电活动时空离散区的算法Volta AF Xplorer)两种术式的复发率。研究的主要终点为单次消融术后12月无房颤复发,次要终点为无任何房性心律失常事件,安全性终点为死亡、脑血管事件或治疗相关严重不良事件。在主要终点上个体化消融组显著优于解剖消融组(88%比70%,p<0.0001),在次要终点和安全性终点上两组无显著差异。
Nature Medicine,
2025-2-14.
DOI: 10.1038/s41591-025-03517-w
Abstract:
Abstract Although pulmonary vein isolation (PVI) has become the cornerstone ablation procedure for atrial fibrillation (AF), the optimal ablation procedure for persistent and long-standing persistent AF remains elusive. Targeting spatio-temporal …
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Abstract Although pulmonary vein isolation (PVI) has become the cornerstone ablation procedure for atrial fibrillation (AF), the optimal ablation procedure for persistent and long-standing persistent AF remains elusive. Targeting spatio-temporal electrogram dispersion in a tailored procedure has been suggested as a potentially beneficial alternative to a conventional PVI-only procedure. In this multicenter, randomized, controlled, double-blind, superiority trial, patients with drug-refractory persistent AF were randomly assigned to a tailored ablation procedure targeting areas of spatio-temporal dispersion, as detected by an artificial intelligence (AI) algorithm, in addition to PVI (tailored arm, n = 187, 23% women) or to a conventional PVI-only procedure (anatomical arm, n = 183, 19% women). The primary efficacy endpoint was freedom from documented AF with or without antiarrhythmic drugs at 12 months after a single ablation procedure. Secondary endpoints included freedom from any atrial arrhythmic events, and the secondary composite safety endpoint consisted of death, cerebrovascular events, or treatment-related serious adverse events. One year post-procedure, the trial met its primary efficacy endpoint, which was achieved in 88% of patients in the tailored arm compared with 70% of patients in the anatomical arm (log-rank P < 0.0001 for superiority). However, no significant difference between arms was observed for the freedom from any atrial arrhythmia endpoint after one ablation. The safety endpoint did not differ between arms, with procedure and ablation times being twice as long in the tailored arm. These results show that AI-guided ablation of spatio-temporal dispersion areas in addition to PVI is superior to PVI alone in eliminating AF at 1-year follow-up in patients with persistent and long-standing persistent AF. Ablation of subsequent organized atrial tachycardias may be needed to maintain sinus rhythm long term. ClinicalTrials.gov identifier: NCT04702451.
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