Frontiers of Medicine最新文献

Immune cells in diabetic wound repair: the key to better wound management. 免疫细胞在糖尿病创面修复中的作用：改善创面管理的关键。

IF 3.5 3区医学

Frontiers of Medicine Pub Date : 2025-12-27 DOI: 10.1007/s11684-025-1190-y

Yi Ru, Yunxi Cai, Guangyuan Cheng, Xiaoxuan Ma, Jingsi Jiang, Jiankun Song, Ying Luo, Ying Zhang, Qi Zheng, Mingxia Wang, Chunjie Gao, Bin Li, Le Kuai, Yue Luo, Zhan Zhang

{"title":"Immune cells in diabetic wound repair: the key to better wound management.","authors":"Yi Ru, Yunxi Cai, Guangyuan Cheng, Xiaoxuan Ma, Jingsi Jiang, Jiankun Song, Ying Luo, Ying Zhang, Qi Zheng, Mingxia Wang, Chunjie Gao, Bin Li, Le Kuai, Yue Luo, Zhan Zhang","doi":"10.1007/s11684-025-1190-y","DOIUrl":"https://doi.org/10.1007/s11684-025-1190-y","url":null,"abstract":"Chronic diabetic ulcers (DUs) pose a significant clinical challenge with high amputation and mortality rates, impacting over 131 million people worldwide and incurring approximately $755 billion in annual healthcare costs. Immune cells play indispensable roles in orchestrating wound healing; however, existing reviews often overlook the temporal heterogeneity of immune cell subsets in DUs. To bridge this gap, this review comprehensively examines the roles and characteristics of immune cells in DUs healing, involving monocytes, macrophages, dendritic cells, neutrophils, mast cells, B cells, T cells, and natural killer cells, with a focus on their distribution and dysregulation throughout different stages of wound healing. Furthermore, we highlight advances in immune cell-targeted modulation and the emerging therapeutic promise of topical anti-cytokine biologics in diabetic wound care. We uniquely emphasize the dynamic transitions of monocyte subsets and offer a systematic evaluation of the controversial roles of macrophage M1/M2 polarization. This review underscores emerging therapeutic strategies that leverage immune cell modulation, offering insights into more effective DU management.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

"Zero-distance" photocrosslinking: a paradigm shift in probing DNA-protein dynamics. “零距离”光交联：探测dna -蛋白质动力学的范式转变。

IF 3.5 3区医学

Frontiers of Medicine Pub Date : 2025-12-27 DOI: 10.1007/s11684-025-1188-5

Fengting Guo, Sisi Fan, Xueqian Ouyang, Lanfang Li, Lifang Li

引用次数: 0

ILKAP drives hepatocellular carcinoma progression by modulating PGAM1-mediated glycolytic reprogramming. ILKAP通过调节pgam1介导的糖酵解重编程驱动肝癌进展。

IF 3.5 3区医学

Frontiers of Medicine Pub Date : 2025-12-27 DOI: 10.1007/s11684-025-1178-7

Juejiashan Li, Yihong Chen, Qiyi Qian, Yating Gao, Nana Zhou, Xiaoyan Li, Qiuran Xu, Dongsheng Huang, Wenhu Chen

{"title":"ILKAP drives hepatocellular carcinoma progression by modulating PGAM1-mediated glycolytic reprogramming.","authors":"Juejiashan Li, Yihong Chen, Qiyi Qian, Yating Gao, Nana Zhou, Xiaoyan Li, Qiuran Xu, Dongsheng Huang, Wenhu Chen","doi":"10.1007/s11684-025-1178-7","DOIUrl":"https://doi.org/10.1007/s11684-025-1178-7","url":null,"abstract":"Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, necessitating novel therapeutic targets. This study explores the oncogenic role of integrin-linked kinase-associated phosphatase (ILKAP) in HCC and its underlying mechanisms. Database analyses (TCGA, UALCAN) revealed ILKAP overexpression in HCC, correlating with poor prognosis. Functional assays demonstrated that ILKAP knockdown significantly suppressed HCC cell proliferation and migration in vitro, while xenograft models confirmed its role in tumor growth in vivo. RNA sequencing identified 357 differentially expressed genes (DEGs), including 48 protein-coding DEGs, with glycolytic enzyme PGAM1 notably downregulated upon ILKAP silencing. ILKAP and PGAM1 expression were positively correlated in HCC tissues, and elevated PGAM1 levels were linked to worse survival. Notably, restoring PGAM1 in ILKAP-knockdown cells rescued proliferation and invasion, underscoring PGAM1's critical role in ILKAP-mediated tumor progression. ILKAP depletion also reduced extracellular acidification rates and altered glycolysis-related gene expression, highlighting its role in metabolic reprogramming. These findings suggest that ILKAP drives HCC malignancy by modulating PGAM1 and glycolysis, providing a potential therapeutic target for HCC treatment. Further elucidation of the ILKAP-PGAM1 axis may offer new strategies for liver cancer management.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Association of oral frailty and gut microbiota with hypertension: cross-sectional results in the Shika study. 口腔脆弱和肠道微生物群与高血压的关系：Shika研究的横断面结果。

IF 3.5 3区医学

Frontiers of Medicine Pub Date : 2025-12-27 DOI: 10.1007/s11684-025-1169-8

Fumihiko Suzuki, Ren Mizoguchi, Shigehiro Karashima, Yasuo Ikagawa, Hiromasa Tsujiguchi, Akinori Hara, Sakae Miyagi, Thao Thi Thu Nguyen, Atsushi Asai, Koji Katano, Tomoko Kasahara, Kuniko Sato, Masaharu Nakamura, Yukari Shimizu, Aki Shibata, Keita Suzuki, Takayuki Kannon, Noriyoshi Ogino, Hirohito Tsuboi, Atsushi Tajima, Shigefumi Okamoto, Hiroyuki Nakamura

{"title":"Association of oral frailty and gut microbiota with hypertension: cross-sectional results in the Shika study.","authors":"Fumihiko Suzuki, Ren Mizoguchi, Shigehiro Karashima, Yasuo Ikagawa, Hiromasa Tsujiguchi, Akinori Hara, Sakae Miyagi, Thao Thi Thu Nguyen, Atsushi Asai, Koji Katano, Tomoko Kasahara, Kuniko Sato, Masaharu Nakamura, Yukari Shimizu, Aki Shibata, Keita Suzuki, Takayuki Kannon, Noriyoshi Ogino, Hirohito Tsuboi, Atsushi Tajima, Shigefumi Okamoto, Hiroyuki Nakamura","doi":"10.1007/s11684-025-1169-8","DOIUrl":"https://doi.org/10.1007/s11684-025-1169-8","url":null,"abstract":"Although recent studies have reported the association between toxins produced by certain gut microbiota and elevated blood pressure, the relationship between oral frailty (OF) and gut microbiota has rarely been investigated. The purpose of this study was to epidemiologically investigate the relationship between the combination of OF and specific gut microbiota on hypertension in the residents of Shika Town, Ishikawa Prefecture, Japan. A total of 322 residents aged ⩾ 50 years in Shika Town agreed to participate and met the criteria. The OF was evaluated difficulty in chewing and swallowing, oral dryness, number of remaining teeth, and frequency of tooth brushing. Blood pressure was measured using an automatic digital blood pressure meter. Next-generation sequencing was used to analyze the gut microbiota. A two-way analysis of covariance revealed a significant interaction between the two OF groups and the two hypertension groups on Megamonas. The binomial logistic regression analysis stratified by OF revealed a positive correlation between Megamonas and hypertension (OR 1.317; P = 0.023). This cross-sectional epidemiological study of the local residents revealed that the abundance of Megamonas in the OF group was significantly higher in the hypertension group than in the normotension group; however, no such relationship was observed in the non-OF group.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cerebral organoids and organoid intelligence: ethical challenges and governance pathway. 脑类器官和类器官智能：伦理挑战和治理途径。

IF 3.5 3区医学

Frontiers of Medicine Pub Date : 2025-12-27 DOI: 10.1007/s11684-025-1193-8

Huiyu Luo, Xiangdong Xie

引用次数: 0

Prognostic utility of baseline ASCL1/INSM1 expression and neutrophil-lymphocyte ratio in unresectable SCLC treated with first-line chemoimmunotherapy with or without radiotherapy. 基线ASCL1/INSM1表达和中性粒细胞淋巴细胞比值在一线化疗免疫治疗伴或不伴放疗的不可切除SCLC中的预后价值

IF 3.5 3区医学

Frontiers of Medicine Pub Date : 2025-12-27 DOI: 10.1007/s11684-025-1187-6

Yanli Zhu, Sheng Li, Hanxiao Chen, Guangqian Ji, Haiyue Wang, Xinting Diao, Xiuli Ma, Minglei Zhuo, Dongmei Lin

{"title":"Prognostic utility of baseline ASCL1/INSM1 expression and neutrophil-lymphocyte ratio in unresectable SCLC treated with first-line chemoimmunotherapy with or without radiotherapy.","authors":"Yanli Zhu, Sheng Li, Hanxiao Chen, Guangqian Ji, Haiyue Wang, Xinting Diao, Xiuli Ma, Minglei Zhuo, Dongmei Lin","doi":"10.1007/s11684-025-1187-6","DOIUrl":"https://doi.org/10.1007/s11684-025-1187-6","url":null,"abstract":"While immune checkpoint inhibitors have revolutionized small cell lung carcinoma (SCLC) management, clinical benefits remain restricted to a subset of patients. This study investigates baseline biomarkers for predicting outcomes in unresectable SCLC patients receiving first-line chemoimmunotherapy with or without radiotherapy. We retrospectively analyzed treatment-naïve, unresectable SCLC patients undergoing first-line chemoimmunotherapy at Peking University Cancer Hospital (between June 2020 and November 2022). Clinicopathological parameters, pretreatment hematologic indices, and immunohistochemical profiles (ASCL1, NEUROD1, POU2F3, YAP1, PD-L1, CD8, MHC-I, and Rb) were correlated with survival outcomes using Cox proportional hazards models. Composite biomarker strategies were evaluated for therapeutic stratification. A total of 143 SCLC patients were included (LS=41, ES=102). The SCLC-A subtype demonstrated optimal median overall survival (OS) than other subtypes (18 months vs. 11 months, P = 0.02), and SCLC-P patients exhibited poorer prognosis than NE phenotypes (SCLC-A, SCLC-N, SCLC-AN). Multivariate analysis identified VALSG stage (P = 0.02) and bone metastases (P = 0.045) as independent OS predictors in the entire cohort. Patients stratified by ASCL1/INSM1 positivity and NLR thresholds showed markedly divergent outcomes, with ASCL1+/NLRlow group and or INSM1+/NLRlow group achieving superior OS in the overall cohort, LS-SCLC, and ES-SCLC. The ASCL1/INSM1-NLR composite biomarker stratifies survival outcomes for unresectable SCLC patients treated with first-line chemoimmunotherapy with or without radiotherapy. Prospective multicenter validation is required.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comparative analysis reveals distinct molecular heterogeneity in vaginal cells between recurrent and primary pelvic organ prolapse patients. 对比分析揭示了复发性和原发性盆腔器官脱垂患者阴道细胞的明显分子异质性。

IF 3.5 3区医学

Frontiers of Medicine Pub Date : 2025-12-27 DOI: 10.1007/s11684-025-1180-0

Yaqian Li, Yiwei Zhang, Rui Wang, Rusha Yin, Wei Liu, Lan Zhu

{"title":"Comparative analysis reveals distinct molecular heterogeneity in vaginal cells between recurrent and primary pelvic organ prolapse patients.","authors":"Yaqian Li, Yiwei Zhang, Rui Wang, Rusha Yin, Wei Liu, Lan Zhu","doi":"10.1007/s11684-025-1180-0","DOIUrl":"https://doi.org/10.1007/s11684-025-1180-0","url":null,"abstract":"High recurrence rate in pelvic organ prolapse (POP) seriously increases treatment difficulty and elucidating the mechanisms is critical for developing targeted therapies. However, its underlying molecular mechanisms remain unclear. Using a single-cell RNA sequencing dataset, we analyzed vaginal fibroblasts, smooth muscle cells and macrophages in recurrent and primary POP. Comparative analysis of differentially expressed genes (DEGs) showed recurrent and primary POP shared fewer DEGs, while exhibiting more subtype-specific DEGs, confirming substantial molecular heterogeneity. Further analysis revealed that shared fibroblast DEGs in both POP subtypes were primarily enriched in collagen fibril organization, while recurrent POP showed uniquely upregulation of genes related to collagen metabolism and leukocyte migration. NKD2+ myofibroblasts were higher in recurrent POP compared to primary POP. In macrophages, shared upregulated DEGs in both groups were enriched in ECM remodeling and TGF-β signaling, highlighting conserved roles of macrophages-fibroblast interaction. Whereas, certain genes, such as fibrotic-related genes, were specifically upregulated in recurrent POP, implicating potential distinct fibrotic mechanisms in recurrence. Furthermore, the proportion of M2-like macrophages in recurrent POP was higher than primary POP. These findings reveal a potential shift toward pro-fibrotic and tissue-remodeling immune microenvironment in recurrent POP, providing novel insights into the cellular and molecular drivers of POP recurrence.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Risk prediction and therapeutic targets for incident pulmonary hypertension: a large-scale proteomic profiling and Mendelian randomization study. 突发肺动脉高压的风险预测和治疗目标：一项大规模蛋白质组学分析和孟德尔随机化研究。

IF 3.5 3区医学

Frontiers of Medicine Pub Date : 2025-12-27 DOI: 10.1007/s11684-025-1183-x

Yuanyuan Zhang, Yan Zhang, Sisi Yang, Yu Huang, Yanjun Zhang, Ziliang Ye, Hao Xiang, Xiaoqin Gan, Fan Fan Hou, Xianhui Qin

{"title":"Risk prediction and therapeutic targets for incident pulmonary hypertension: a large-scale proteomic profiling and Mendelian randomization study.","authors":"Yuanyuan Zhang, Yan Zhang, Sisi Yang, Yu Huang, Yanjun Zhang, Ziliang Ye, Hao Xiang, Xiaoqin Gan, Fan Fan Hou, Xianhui Qin","doi":"10.1007/s11684-025-1183-x","DOIUrl":"https://doi.org/10.1007/s11684-025-1183-x","url":null,"abstract":"We aimed to identify plasma proteins associated with pulmonary hypertension (PH) risk, discover potential therapeutic targets for PH, and develop and validate a protein-based prediction model. The development cohort included 38 499 UK Biobank participants from England (split into 70% training and 30% testing set), while the validation cohort comprised 5021 participants from Scotland and Wales. LASSO regression was used to identify predictive proteins in the training set, with model performance assessed using Harrell's C-index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) in the testing and validation cohorts. We developed a 30-protein risk score, identifying RGMA and NPC2 as causal factors and potential therapeutic targets. Endothelin-1 emerged as a central hub in the protein-protein interaction network. In the testing set, the PH protein risk score demonstrated superior predictive performance for PH risk (C-index = 0.873, 95% CI 0.846-0.900) compared to a basic model (age and sex; C-index = 0.761, 95% CI 0.726-0.795) and a clinical risk model (C-index = 0.843, 95% CI 0.815-0.870). Adding the PH protein risk score to clinical risk factors significantly improved 10-year PH risk reclassification (NRI = 0.258, IDI = 0.053). Similar performance was observed in the validation cohort. These findings underscore the clinical utility of protein biomarkers for PH risk assessment and identify RGMA and NPC2 as promising therapeutic targets.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Prognostic value of ultrafiltration rate variability in maintenance hemodialysis patients: a prospective cohort study. 超滤率变异性在维持性血液透析患者中的预后价值：一项前瞻性队列研究。

IF 3.5 3区医学

Frontiers of Medicine Pub Date : 2025-12-27 DOI: 10.1007/s11684-025-1168-9

Jinbo Yu, Xiaohong Chen, Wuhua Jiang, Yang Li, Yuxin Nie, Bo Shen, Jianzhou Zou, Yaqiong Wang, Xiaoqiang Ding

{"title":"Prognostic value of ultrafiltration rate variability in maintenance hemodialysis patients: a prospective cohort study.","authors":"Jinbo Yu, Xiaohong Chen, Wuhua Jiang, Yang Li, Yuxin Nie, Bo Shen, Jianzhou Zou, Yaqiong Wang, Xiaoqiang Ding","doi":"10.1007/s11684-025-1168-9","DOIUrl":"https://doi.org/10.1007/s11684-025-1168-9","url":null,"abstract":"This single-center prospective cohort study establishes ultrafiltration rate variability (quantified by coefficient of variation, UFRCV) as an independent predictor of all-cause and cardiovascular mortality in maintenance hemodialysis patients. While absolute ultrafiltration rate thresholds represent established risk factors, dynamic fluid removal fluctuations remain prognostically uncharacterized. We longitudinally monitored ultrafiltration rate patterns during a 90-day observation period in 202 hemodialysis patients (median follow-up: 38.7 months). Stratification by median UFRCV (0.187) revealed significantly reduced survival among patients with elevated variability. This association demonstrated particular clinical significance in elderly individuals (> 60 years), those with recurrent intradialytic hypotension, and subjects exhibiting elevated predialysis systolic blood pressure variability. Notably, UFRCV exhibited stronger mortality prediction in patients with lower mean ultrafiltration volumes (< 2469 mL), indicating that current static ultrafiltration rate targets inadequately reflect dynamic hemodynamic vulnerability. These findings underscore the imperative to integrate ultrafiltration rate variability metrics into personalized volume management frameworks-a parameter currently absent from dialysis adequacy guidelines. Collectively, UFRCV assessment emerges as a critical indicator of subclinical hemodynamic compromise, providing pivotal insights for refining hemodynamic risk stratification in maintenance hemodialysis populations.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clinical trial landscape of malignant peripheral nerve sheath tumors: challenges and opportunities. 恶性周围神经鞘肿瘤的临床试验前景：挑战与机遇。

IF 3.5 3区医学

Frontiers of Medicine Pub Date : 2025-12-27 DOI: 10.1007/s11684-025-1174-y

Guo Zhao, Yale Jiang, Jiaxiu Ma, Shuhang Wang, Ning Li

引用次数: 0