IF 10.7

MedComm Pub Date : 2026-04-08 eCollection Date: 2026-04-01 DOI: 10.1002/mco2.70736

Dongming Wang, Zhonghe Shao, Zhaomin Chen, Xingjie Hao, Wenzhen Li

{"title":"Chronotype, Genetic Risk, Lifestyle, and Risk of Depression and Anxiety: A Prospective Cohort Study.","authors":"Dongming Wang, Zhonghe Shao, Zhaomin Chen, Xingjie Hao, Wenzhen Li","doi":"10.1002/mco2.70736","DOIUrl":"https://doi.org/10.1002/mco2.70736","url":null,"abstract":"We aimed to evaluate associations of chronotype, genetic risk, and lifestyle with depression and anxiety. A total of 242,391 participants without anxiety and depression at baseline in UK Biobank were included. During a total of 3,393,260.1 and 1,371,872.8 person-years follow-up, we found 11,824 (4.88%) incident depression and 10,051 (4.15%) incident anxiety cases, respectively. Compared with definite morning group, individuals with intermediate (HR = 1.09, 95% CI = 1.04‒1.13) and definite evening chronotype (HR = 1.45, 95% CI = 1.36‒1.55) have higher risks of depression, and individuals with definite evening chronotype (HR = 1.27, 95% CI = 1.18‒1.37) have a higher risk of anxiety. We found joint association between chronotype and genetic risk, those with high genetic risk and definite evening chronotype had the highest risk of depression (HR = 2.01, 95% CI = 1.81‒2.23) and anxiety (HR = 1.40, 95% CI = 1.24‒1.58). We also found joint association between chronotype and lifestyle, those with least healthy lifestyle and definite evening chronotype had the highest risk of depression (HR = 1.99, 95% CI = 1.65‒2.40) and anxiety (HR = 1.69, 95% CI = 1.36‒2.10). Individuals with evening chronotype are associated with higher risks of depression and anxiety.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 4","pages":"e70736"},"PeriodicalIF":10.7,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13062636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147679564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Japanese Macaque as a Diabetes Recipient Animal Model for Porcine Islet Xenotransplantation. 日本猕猴作为猪胰岛异种移植的糖尿病受体动物模型。

IF 10.7

MedComm Pub Date : 2026-04-08 eCollection Date: 2026-04-01 DOI: 10.1002/mco2.70726

Naoaki Sakata, Gumpei Yoshimatsu, Ryo Kawakami, Seiichi Tanaka, Shohta Kodama

{"title":"The Japanese Macaque as a Diabetes Recipient Animal Model for Porcine Islet Xenotransplantation.","authors":"Naoaki Sakata, Gumpei Yoshimatsu, Ryo Kawakami, Seiichi Tanaka, Shohta Kodama","doi":"10.1002/mco2.70726","DOIUrl":"https://doi.org/10.1002/mco2.70726","url":null,"abstract":"Porcine islet xenotransplantation is effective for severe diabetes; however, preclinical studies are essential. In this study, we evaluated the suitability of the Japanese macaque as a recipient model for islet xenotransplantation, including identifying the preferred method to induce diabetes. The safety and stability of the following four models to induce diabetes were assessed: Model 1: pancreatectomy, Model 2: pancreatectomy with low-dose streptozotocin (STZ), Model 3: single-injection of STZ, and Model 4: consecutive administrations of low-dose STZ. Diabetes was induced in all four models. The blood glucose level after induction of diabetes was 225.32 ± 46.49 mg/dL in Model 1, 209.64 ± 64.36 mg/dL in Model 2, 175.51 ± 45.18 mg/dL in Model 3, and 139.22 ± 6.31 mg/dL in Model 4. Regarding safety, Models 1 and 2 involved invasive surgery with postoperative concerns. Model 3 induced diabetes in the Japanese macaques; however, the preferable dose of STZ was individual dependent. Among the models, Model 4 was preferable regarding safety and stability. Finally, we performed porcine islet xenotransplantation in a diabetic monkey in Model 4 and evaluated the therapeutic effects of this treatment. In conclusion, the Japanese macaque might be a possible recipient model for porcine islet xenotransplantation.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 4","pages":"e70726"},"PeriodicalIF":10.7,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13062647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147679602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multimodal Deep Learning for Pulmonary Nodule Detection on Chest Radiography in High-Risk Adults, With Secondary Validation for All-Cause and Cause-Specific Mortality Prediction: A Multicenter Cohort Study. 多模态深度学习用于高风险成人胸片肺结节检测，对全因和病因特异性死亡率预测进行二次验证：一项多中心队列研究。

IF 10.7

MedComm Pub Date : 2026-04-08 eCollection Date: 2026-04-01 DOI: 10.1002/mco2.70730

Junxian Li, Yuchen Xing, Ximin Gao, Ya Liu, Liwen Zhang, Yubei Huang, Pengyu Zhang, Zhaoxiang Ye, Meng Wang, Fengju Song

{"title":"Multimodal Deep Learning for Pulmonary Nodule Detection on Chest Radiography in High-Risk Adults, With Secondary Validation for All-Cause and Cause-Specific Mortality Prediction: A Multicenter Cohort Study.","authors":"Junxian Li, Yuchen Xing, Ximin Gao, Ya Liu, Liwen Zhang, Yubei Huang, Pengyu Zhang, Zhaoxiang Ye, Meng Wang, Fengju Song","doi":"10.1002/mco2.70730","DOIUrl":"https://doi.org/10.1002/mco2.70730","url":null,"abstract":"Chest radiographs (CXRs) may encode prognostic signals beyond pulmonary nodule detection. We developed LungProNet, a multimodal deep-learning (DL) model that fuses CXR features with four epidemiologic variables (age, sex, smoking history, and family history) for pulmonary nodule detection as the primary task, with secondary validation for all-cause and cause-specific mortality prediction. LungProNet was trained and internally validated on Tianjin Lung Cancer Imaging Dataset (TLCID) (70/30; n = 2852/1227) and externally validated on ChestDR (n = 4848), with stratified analyses across epidemiologic strata. Discrimination was quantified by area under the curve (AUC) (95% confidence intervals), with accuracy, sensitivity, and specificity reported, and results were benchmarked against contemporary machine learning/DL baselines. The pretrained multimodal encoder was transferred without fine-tuning to the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) (n = 24,697); its fused embeddings were used as covariates in Cox proportional-hazards models, and time-dependent AUCs were evaluated at 1-12 years. For nodule detection, AUCs were 0.979 (0.975-0.982) in TLCID and 0.849 (0.835-0.862) in ChestDR; the TLCID stratified model reached 0.990 (0.984-0.994). In PLCO, AUCs were 0.925 (0.892-0.952) for all-cause mortality and 0.939-0.985 for cardiac-, lung cancer-, and Chronic Obstructive Pulmonary Disease (COPD)-cause mortality, with robust subgroup performance. These results support CXR-based nodule flagging within screening workflows and suggest secondary opportunistic risk stratification potential.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 4","pages":"e70730"},"PeriodicalIF":10.7,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13062638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147679578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Single-Cell and Spatial Omics: Methods and Applications. 单细胞和空间组学：方法和应用。

IF 10.7

MedComm Pub Date : 2026-04-06 eCollection Date: 2026-04-01 DOI: 10.1002/mco2.70713

Xiaoping Cen, Xiaolan Huang, Enjin Deng, Xue Gong, Na Tan, Jifeng Ye, Yin Wang, Roland Eils, Qun Luo, Yixue Li, Fangfang Qu

{"title":"Single-Cell and Spatial Omics: Methods and Applications.","authors":"Xiaoping Cen, Xiaolan Huang, Enjin Deng, Xue Gong, Na Tan, Jifeng Ye, Yin Wang, Roland Eils, Qun Luo, Yixue Li, Fangfang Qu","doi":"10.1002/mco2.70713","DOIUrl":"https://doi.org/10.1002/mco2.70713","url":null,"abstract":"Single-cell and spatial omics have revolutionized biomedical research by enabling high-resolution molecular profiling across cells and tissues, thereby overcoming key limitations of bulk sequencing and revealing unprecedented cellular heterogeneity and spatial organization central to development, homeostasis, and disease. Specifically, advances in high-throughput, subcellular, and multiomics profiling are promoting the field toward deeper insights. In parallel, computational progress, including generative artificial intelligence (AI) and foundation models, is developing rapidly for manipulating multimodal multiomics data. These advancements have been applied to diverse diseases and biological systems, facilitating innovative biomedical findings. However, a significant gap persists between rapid methodological advances and their systematic application for deciphering human biology and pathology. This review synthesizes recent breakthroughs in single-cell and spatial technologies and surveys computational methods, including AI-driven approaches, foundation models, and multi-omics integration algorithms for both single-cell and spatial analyses. We then summarize representative applications across major human organ systems in health and disease, highlighting opportunities for biomarker discovery, therapeutic target identification, and precision medicine. Finally, we discuss current challenges and future directions for bridging technological innovation with robust biomedical discovery and translational impact. This review provides a vital guide for researchers in the field, offering critical insights for accelerating the translation of single-cell and spatial omics.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 4","pages":"e70713"},"PeriodicalIF":10.7,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13053676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147641050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neoadjuvant Toripalimab Plus Axitinib for Nonmetastatic Clear Cell Renal Cell Carcinoma With Tumor Thrombus: A Combined Analysis of Two Phase II Clinical Trials. 新辅助托利帕单抗加阿西替尼治疗非转移性透明细胞肾细胞癌伴肿瘤血栓：两项II期临床试验的综合分析。

IF 10.7

MedComm Pub Date : 2026-04-06 eCollection Date: 2026-04-01 DOI: 10.1002/mco2.70720

Cheng Peng, Zhuolong Wu, Yaohui Wang, Qiyang Liang, Dongxing Wang, Houming Zhao, Jinhang Li, Xiuzheng Yue, Yibo Zhang, Jialong Song, Changwei Shi, Haiyi Wang, Guoqiang Yang, Baojun Wang, Qingbo Huang, Xu Zhang, Xin Ma, Jiwei Huang, Liangyou Gu

{"title":"Neoadjuvant Toripalimab Plus Axitinib for Nonmetastatic Clear Cell Renal Cell Carcinoma With Tumor Thrombus: A Combined Analysis of Two Phase II Clinical Trials.","authors":"Cheng Peng, Zhuolong Wu, Yaohui Wang, Qiyang Liang, Dongxing Wang, Houming Zhao, Jinhang Li, Xiuzheng Yue, Yibo Zhang, Jialong Song, Changwei Shi, Haiyi Wang, Guoqiang Yang, Baojun Wang, Qingbo Huang, Xu Zhang, Xin Ma, Jiwei Huang, Liangyou Gu","doi":"10.1002/mco2.70720","DOIUrl":"https://doi.org/10.1002/mco2.70720","url":null,"abstract":"Neoadjuvant immunotherapy-based combination holds promises in reducing surgical risk and improving survival for renal cell carcinoma (RCC) with venous tumor thrombus (VTT). However, its role in RCC-VTT has been less explored. To evaluate the efficacy and safety of neoadjuvant toripalimab plus axitinib in nonmetastatic RCC-VTT, we conducted a combined analysis of two Phase II trials with similar design. Thirty-four patients with nonmetastatic clear cell RCC (ccRCC) and Mayo Level 0-IV VTT were enrolled. Toripalimab plus axitinib was administered for up to 12 weeks before surgery. The primary endpoint was objective response rate (ORR). In this study, the ORR and disease control rates were 41% (14 out of 34) and 97% (33 out of 34), respectively. 47% (16 out of 34) patients experienced a reduction in VTT levels. Grade 3 treatment-related adverse events (TRAEs) occurred in 24% (eight out of 34) patients, and no Grade 4 or 5 TRAEs were observed. Thirty patients were eligible for surgery, and the surgical strategy was simplified in 53% (16 out of 30) patients. One-year disease-free survival and overall survival were 76.7% (95% CI, 59.1-88.2%) and 91.2% (95% CI, 77.0-97.0%), respectively. Multiomics analysis revealed the nonresponder group exhibited significant tumor heterogeneity and a stroma-characterized tumor microenvironment. In conclusion, neoadjuvant toripalimab plus axitinib was clinically active and safe in patients with nonmetastatic ccRCC-VTT.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 4","pages":"e70720"},"PeriodicalIF":10.7,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13053665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147641047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lycorine Derivative Inhibits SARS-CoV-2 Replication by Reducing -1 Programmed Ribosomal Frameshifting via Targeting ZAP. 石蒜碱衍生物通过靶向ZAP减少-1程序性核糖体移框抑制SARS-CoV-2复制

IF 10.7

MedComm Pub Date : 2026-04-06 eCollection Date: 2026-04-01 DOI: 10.1002/mco2.70715

Tingfu Du, Ruixue Liu, Xintian Zhang, Longying Shen, Cong Tang, Junbin Wang, Yu Cheng, Wenhai Yu, Bin Yin, Shuaiyao Lu, Xiandao Pan, Xiaozhong Peng

{"title":"Lycorine Derivative Inhibits SARS-CoV-2 Replication by Reducing -1 Programmed Ribosomal Frameshifting via Targeting ZAP.","authors":"Tingfu Du, Ruixue Liu, Xintian Zhang, Longying Shen, Cong Tang, Junbin Wang, Yu Cheng, Wenhai Yu, Bin Yin, Shuaiyao Lu, Xiandao Pan, Xiaozhong Peng","doi":"10.1002/mco2.70715","DOIUrl":"https://doi.org/10.1002/mco2.70715","url":null,"abstract":"The ongoing evolution of SARS-CoV-2 and its immune-evading variants underscores an urgent requirement for broad-spectrum antiviral drugs. In this study, a series of lycorine derivatives was synthesized. This led to the identification of compound 7 as a promising antiviral candidate. Compound 7 exhibited potent inhibitory activity against SARS-CoV-2 and its variants, including Alpha, Beta, Delta, and Omicron, in vitro. The antiviral efficacy of compound 7 was then validated in vivo. Treatment with compound 7 significantly reduced viral loads and alleviated lung pathologies in SARS-CoV-2-infected hamsters. Mechanistically, compound 7 directly targeted the short isoform of the zinc-finger antiviral protein (ZAP-S) and bound to specific residues (E111, E115, and F549). This result was confirmed using cellular thermal shift assays, bio-layer interferometry, and mutagenesis studies. This interaction enhanced the ZAP-S stability and disrupted -1 programmed ribosomal frameshifting (-1PRF), a critical process for viral polyprotein synthesis. The antiviral activity of compound 7 was ZAP-S-dependent, as ZAP-S knockdown abolished its efficacy while overexpression enhanced it. These results established compound 7 as a novel antiviral candidate that can combat SARS-CoV-2 and its variants by targeting ZAP to inhibit -1PRF. This compound, therefore, represents a promising therapeutic strategy.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 4","pages":"e70715"},"PeriodicalIF":10.7,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13053664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147641062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction to "AMPK-Upregulated microRNA-708 Plays as a Suppressor of Cellular Senescence and Aging Via Downregulating Disabled-2 and mTORC1 Activation". 对“ampk上调的microRNA-708通过下调Disabled-2和mTORC1激活抑制细胞衰老和衰老”的更正。

IF 10.7

MedComm Pub Date : 2026-04-06 eCollection Date: 2026-04-01 DOI: 10.1002/mco2.70724

引用次数: 0

Prognostic Implications of Programmed Cell Death Ligand 1 Expression, Cluster of Differentiation 8-Positive T-Cell Infiltration, and Related Immunophenotypes in Invasive Mucinous Adenocarcinoma of the Lung: A Multicenter Study. 程序性细胞死亡配体1表达、分化簇8阳性t细胞浸润和相关免疫表型在侵袭性肺粘液腺癌中的预后意义：一项多中心研究

IF 10.7

MedComm Pub Date : 2026-04-05 eCollection Date: 2026-04-01 DOI: 10.1002/mco2.70710

Guochao Zhang, Chao Zheng, Jia Jia, Xingchen Li, Lide Wang, Long Zhang, Yuzhuo Zhang, Meng Yue, Shuangping Zhang, Yueping Liu, Liyan Xue, Qi Xue, Jie He

{"title":"Prognostic Implications of Programmed Cell Death Ligand 1 Expression, Cluster of Differentiation 8-Positive T-Cell Infiltration, and Related Immunophenotypes in Invasive Mucinous Adenocarcinoma of the Lung: A Multicenter Study.","authors":"Guochao Zhang, Chao Zheng, Jia Jia, Xingchen Li, Lide Wang, Long Zhang, Yuzhuo Zhang, Meng Yue, Shuangping Zhang, Yueping Liu, Liyan Xue, Qi Xue, Jie He","doi":"10.1002/mco2.70710","DOIUrl":"https://doi.org/10.1002/mco2.70710","url":null,"abstract":"The immune microenvironment of invasive mucinous adenocarcinoma of the lung (IMA), a rare and heterogeneous subtype, remains poorly characterized, limiting insights into its potential response to immunotherapy. In this multicenter study, we systematically evaluated programmed cell death ligand 1 (PD-L1) expression (using tumor proportion score, TPS, and combined positive score, CPS) and cluster of differentiation 8-positive (CD8+) tumor-infiltrating lymphocyte (TIL) infiltration in the largest cohort to date of pathologically confirmed pure IMAs (n = 312), supported by single‑cell transcriptomic analysis. PD-L1 positivity was low (TPS≥1%: 9.0%; CPS≥1: 28.5%). While PD-L1 alone showed no prognostic significance, high CD8+ TIL percentage and density were independent, favorable prognostic factors for relapse-free survival, particularly in patients not receiving adjuvant therapy. By integrating TPS and CD8+ TIL percentage, we established a novel four-category immune phenotype classification that identified a distinct subgroup (Type IV: PD-L1+/CD8+) with significantly better outcomes. Preliminary analysis of 20 patients who received immune checkpoint inhibitors suggested that Type IV patients may derive greater clinical benefit. Single-cell RNA sequencing analyses revealed a paucity of effector CD8+ T cells in IMA. This work defines the unique immune landscape of IMA, introduces a clinically relevant immune phenotyping framework with prognostic and predictive potential, and provides a rationale for future immunotherapeutic strategies in this rare malignancy.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 4","pages":"e70710"},"PeriodicalIF":10.7,"publicationDate":"2026-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13051811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147635438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Peripheral Blood Mononuclear Cells Profiling Revealed Biomarkers That Predict PD-1 Inhibitor-Induced Immune-Related Adverse Events. 外周血单个核细胞谱揭示了预测PD-1抑制剂诱导的免疫相关不良事件的生物标志物。

IF 10.7

MedComm Pub Date : 2026-04-05 eCollection Date: 2026-04-01 DOI: 10.1002/mco2.70721

Jun Wang, Hong Xie, Yuanyuan Gong, Songlin Liu, Yaping Guan, Yuekai Zhang, Qi Xie, Jingyi Wang, Ye Li, Xueqin Zeng, Xi Chen, Chen Wang

{"title":"Peripheral Blood Mononuclear Cells Profiling Revealed Biomarkers That Predict PD-1 Inhibitor-Induced Immune-Related Adverse Events.","authors":"Jun Wang, Hong Xie, Yuanyuan Gong, Songlin Liu, Yaping Guan, Yuekai Zhang, Qi Xie, Jingyi Wang, Ye Li, Xueqin Zeng, Xi Chen, Chen Wang","doi":"10.1002/mco2.70721","DOIUrl":"https://doi.org/10.1002/mco2.70721","url":null,"abstract":"Immune checkpoint inhibitors (ICIs) universally enhance antitumor immunity but endanger a subgroup of patients by triggering immune-related adverse events (irAEs). We profiled the expressions of 41 proteins on peripheral blood mononuclear cells (PBMCs) prior the initiation of immunotherapy. CXCR3 and CCR6 expressions were significantly decreased in PBMC subpopulations from patient with irAEs but not from those who responded to PD-1 inhibitors. The expression of CCR6 in a NK cell subpopulation serves exclusively as a biomarker to differentiate patients who developed irAEs. Interestingly, circulating ligands of CXCR3, including CXCL9, CXCL10, and CXCL11, were significantly increased in patients who later developed irAEs after PD-1 inhibitor treatment. The decreases of CXCR3 in three T cell subpopulations and decreases of CCR6 in a NK cell subpopulation were further validated in two independent external cohorts. Moreover, multiple proteins in PBMCs, distinct from the irAE-predicting biomarkers, exhibited differential expression levels corresponding to the differential responses to the PD-1 inhibitors. Via multiple independent cohorts, our study revealed crucial roles of CXCR3 and CCR6 in PD-1-induced irAEs, provided potential circulating biomarkers associated with toxicity and responses of PD-1 inhibitors and further sculptured the landscape of immune cell heterogeneity via focusing on PBMC subpopulations.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 4","pages":"e70721"},"PeriodicalIF":10.7,"publicationDate":"2026-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13052260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147635394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Differential Mortality Risk by Age in Males and Females With Steatotic Liver Disease. 男性和女性脂肪变性肝病患者的年龄死亡率差异

IF 10.7

MedComm Pub Date : 2026-04-05 eCollection Date: 2026-04-01 DOI: 10.1002/mco2.70677

Taotao Yan, Nicholas Chien, Vy H Nguyen, Isaac Le, Surya Teja Gudapati, Angela Chau, Xinrong Zhang, Scott Barnett, Sovann Linden, Linda Henry, Ramsey Cheung, Mindie H Nguyen

{"title":"Differential Mortality Risk by Age in Males and Females With Steatotic Liver Disease.","authors":"Taotao Yan, Nicholas Chien, Vy H Nguyen, Isaac Le, Surya Teja Gudapati, Angela Chau, Xinrong Zhang, Scott Barnett, Sovann Linden, Linda Henry, Ramsey Cheung, Mindie H Nguyen","doi":"10.1002/mco2.70677","DOIUrl":"https://doi.org/10.1002/mco2.70677","url":null,"abstract":"Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major cause of premature mortality, but data on sex differences in mortality remain limited. We compared the overall, nonliver-related, and liver-related mortality rates per 1000 person-years in MASLD patients by sex. Propensity score matching (PSM) yielded 3579 pairs of females and males with balanced characteristics from a cohort of 8517 MASLD patients (53.1% female, 46.6% male) seen at Stanford University Medical Center (1995-2023). In the total PSM cohort, the overall (12.68 vs. 12.92), nonliver-related (11.43 vs. 11.60), and liver-related (1.25 vs. 1.32) mortality rates were similar between males and females. However, in age-stratified analyses, females had higher overall (7.99 vs. 4.95, p = 0.02) and nonliver-related (7.20 vs. 4.71, p = 0.05) mortality rates among younger (≤50 years) patients, with opposite direction among the older group with higher overall (21.40 vs. 16.51, p = 0.02) and nonliver-related (19.02 vs. 14.80, p = 0.04) mortality rates in males. In Cox regression analyses, male sex was associated with lower risks of overall and nonliver-related mortality (adjusted hazard ratio [aHR] 0.59 and 0.61) among patients ≤50 years, but with higher risks among those >50 years (aHR 1.32 and 1.30). Sex and age should be considered in the management strategies for people with MASLD.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 4","pages":"e70677"},"PeriodicalIF":10.7,"publicationDate":"2026-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13051813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147635445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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