Lan Zhu, Zichen Zhao, Attilio Di Spiezio Sardo, Maribel Acién, Joel Naftalin, Thierry Van den Bosch, Charleen Sze-Yan Cheung, Dabao Xu, Xiaowu Huang, Grigoris Grimbizis
{"title":"Euro-Chinese consensus on accessory cavitated uterine malformation.","authors":"Lan Zhu, Zichen Zhao, Attilio Di Spiezio Sardo, Maribel Acién, Joel Naftalin, Thierry Van den Bosch, Charleen Sze-Yan Cheung, Dabao Xu, Xiaowu Huang, Grigoris Grimbizis","doi":"10.1097/CM9.0000000000003717","DOIUrl":"https://doi.org/10.1097/CM9.0000000000003717","url":null,"abstract":"","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265395","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}
Xueru Li, Gangfeng Yu, Xiao Zhong, Jiacheng Zhong, Xiangyu Chen, Qinglong Chen, Jinjiang Xue, Xi Yang, Xinchun Zhang, Yao Ling, Yun Xiu, Yaqi Deng, Hongda Li, Wei Mo, Yong Zhu, Ting Zhang, Liangjun Qiao, Song Chen, Fanghui Lu
{"title":"P4HA1 mediates YAP hydroxylation and accelerates collagen synthesis in temozolomide-resistant glioblastoma.","authors":"Xueru Li, Gangfeng Yu, Xiao Zhong, Jiacheng Zhong, Xiangyu Chen, Qinglong Chen, Jinjiang Xue, Xi Yang, Xinchun Zhang, Yao Ling, Yun Xiu, Yaqi Deng, Hongda Li, Wei Mo, Yong Zhu, Ting Zhang, Liangjun Qiao, Song Chen, Fanghui Lu","doi":"10.1097/CM9.0000000000003679","DOIUrl":"https://doi.org/10.1097/CM9.0000000000003679","url":null,"abstract":"<p><strong>Background: </strong>Temozolomide (TMZ) resistance is a significant challenge in treating glioblastoma (GBM). Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers. This study aimed to investigate the mechanism of TMZ chemoresistance by GBM cells reprogramming collagens.</p><p><strong>Methods: </strong>Key extracellular matrix components, including collagens, were examined in paired primary and recurrent GBM samples as well as in TMZ-treated spontaneous and grafted GBM murine models. Human GBM cell lines (U251, TS667) and mouse primary GBM cells were used for in vitro studies. RNA-sequencing analysis, chromatin immunoprecipitation, immunoprecipitation-mass spectrometry, and co-immunoprecipitation assays were conducted to explore the mechanisms involved in collagen accumulation. A series of in vitro and in vivo experiments were designed to assess the role of the collagen regulators prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and yes-associated protein (YAP) in sensitizing GBM cells to TMZ.</p><p><strong>Results: </strong>This study revealed that TMZ exposure significantly elevated Collagen type I (COL I) expression in both GBM patients and murine models. Collagen accumulation sustained GBM cell survival under TMZ-induced stress, contributing to enhanced TMZ resistance. Mechanistically, P4HA1 directly binded to and hydroxylated YAP, preventing ubiquitination-mediated YAP degradation. Stabilized YAP robustly drove collagen type I alpha 1 (COL1A1) transcription, leading to increased collagen deposition. Disruption of the P4HA1-YAP axis effectively reduced COL I deposition, sensitized GBM cells to TMZ, and significantly improved mouse survival.</p><p><strong>Conclusion: </strong>P4HA1 maintained YAP-mediated COL1A1 transcription, leading to collagen accumulation and promoting chemoresistance in GBM.</p>","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246727","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}
Yi Li, Xiang Wang, Sixian Weng, Chenxi Xia, Xuyang Meng, Chenguang Yang, Ying Guo, Zuowei Pei, Haiyang Gao, Fang Wang
{"title":"Cardiomyocyte pyroptosis inhibited by dental pulp-derived mesenchymal stem cells via the miR-19a-3p/IRF-8/MAPK pathway in ischemia-reperfusion.","authors":"Yi Li, Xiang Wang, Sixian Weng, Chenxi Xia, Xuyang Meng, Chenguang Yang, Ying Guo, Zuowei Pei, Haiyang Gao, Fang Wang","doi":"10.1097/CM9.0000000000003623","DOIUrl":"https://doi.org/10.1097/CM9.0000000000003623","url":null,"abstract":"<p><strong>Background: </strong>The protective effect of mesenchymal stem cells (MSCs) on cardiac ischemia-reperfusion (I/R) injury has been widely reported. Dental pulp-derived mesenchymal stem cells (DP-MSCs) have therapeutic effects on various diseases, including diabetes and cirrhosis. This study aimed to determine the therapeutic effects of DP-MSCs on I/R injury and elucidate the underlying mechanism.</p><p><strong>Methods: </strong>Myocardial I/R injury model mice were treated with DP-MSCs or a miR-19a-3p mimic. The infarct volume, fibrotic area, pyroptosis, inflammation level, and cardiac function were measured. Cardiomyocytes exposed to hypoxia-reoxygenation were transfected with the miR-19a-3p mimic, miR-19a-3p inhibitor, or negative control. Pyroptosis and protein expression in the interferon regulatory factor 8/mitogen-activated protein kinase (IRF-8/MAPK) pathway were measured.</p><p><strong>Results: </strong>DP-MSCs protected cardiac function in cardiac I/R-injured mice and inhibited cardiomyocyte pyroptosis. The upregulation of miR-19a-3p protected cardiac function, inhibited cardiomyocyte pyroptosis, and inhibited IRF-8/MAPK signaling in cardiac I/R-injured mice. DP-MSCs inhibited cardiomyocyte pyroptosis and the IRF-8/MAPK signaling by upregulating the miR-19a-3p levels in cardiomyocytes injured by I/R.</p><p><strong>Conclusion: </strong>DP-MSCs protected cardiac function by inhibiting cardiomyocyte pyroptosis through miR-19a-3p under I/R conditions.</p>","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233319","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}
Na Li, Chenyu Luo, Yuqing Chen, Xinran Cheng, Jiahui Luo, Yike Yan, Yuelun Zhang, Bin Lu, Zhiliang He, Kai Song, Dong Wu, Jianbo Tian, Xiaoping Miao, Hongda Chen, Fulan Hu, Min Dai
{"title":"Identification and validation of blood leukocyte DNA methylation biomarkers for early detection of colorectal neoplasm.","authors":"Na Li, Chenyu Luo, Yuqing Chen, Xinran Cheng, Jiahui Luo, Yike Yan, Yuelun Zhang, Bin Lu, Zhiliang He, Kai Song, Dong Wu, Jianbo Tian, Xiaoping Miao, Hongda Chen, Fulan Hu, Min Dai","doi":"10.1097/CM9.0000000000003681","DOIUrl":"https://doi.org/10.1097/CM9.0000000000003681","url":null,"abstract":"<p><strong>Background: </strong>Identifying high-risk populations for colorectal cancer (CRC) is critical for precise screening. This study aimed to develop a novel risk prediction model using blood DNA methylation biomarkers to identify individuals at high risk for colorectal neoplasms.</p><p><strong>Methods: </strong>The biomarker discovery phase involved 106 samples (56 advanced adenomas and 50 healthy controls) collected from the TARGET-C screening cohort between May 2018 and May 2021, which were analyzed using the Illumina Infinium MethylationEPIC v2.0 BeadChip, and 72 samples (22 CRC, 20 advanced adenomas, and 30 healthy controls) collected from clinical cohorts between July 2023 and July 2024, which were analyzed using reduced representation bisulfite sequencing (RRBS). Differentially methylated positions (DMPs) and regions (DMRs) were identified and independently validated in 147 samples (48 CRC, 50 advanced adenomas, and 49 healthy controls) collected from an independent clinical cohort between June 2022 and May 2024 using targeted bisulfite sequencing (TBS). A multi-marker prediction model was constructed using logistic regression, and its diagnostic performance was evaluated through receiver operating characteristic (ROC) curve analysis.</p><p><strong>Results: </strong>In the discovery set, 48 DMPs and 74 DMRs were identified, exhibiting significant differences between CRC/advanced adenomas and healthy controls. Of these, three DMPs and 11 DMRs were successfully validated in the independent set using TBS. Through machine learning approaches, five stable methylation markers were identified and incorporated into a multi-marker prediction model. This model demonstrated excellent diagnostic performance for detecting colorectal neoplasms, with an area under the curve (AUC) of 0.85 (95% confidence interval [CI]: 0.74-0.94), outperforming the traditional lifestyle score (AUC = 0.55, 95% CI: 0.46-0.68). Combining methylation markers with lifestyle scores further improved diagnostic accuracy, achieving an AUC of 0.89. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the significant markers indicated their involvement in tumorigenesis through pathways regulating developmental processes, transcriptional activation, and cancer-related signaling.</p><p><strong>Conclusions: </strong>Blood leukocyte DNA methylation markers show significant potential for identifying high-risk populations for CRC. The identified markers could contribute to the development of novel, effective tools for CRC screening, facilitating precision screening strategies.</p>","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233321","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}
Fan Yang, He Li, Maomao Cao, Xinxin Yan, Siyi He, Shaoli Zhang, Qianru Li, Yi Teng, Changfa Xia, Hongmei Zeng, Yunyong Liu, Wanqing Chen
{"title":"Association between family history and onset age of cancer in China.","authors":"Fan Yang, He Li, Maomao Cao, Xinxin Yan, Siyi He, Shaoli Zhang, Qianru Li, Yi Teng, Changfa Xia, Hongmei Zeng, Yunyong Liu, Wanqing Chen","doi":"10.1097/CM9.0000000000003624","DOIUrl":"https://doi.org/10.1097/CM9.0000000000003624","url":null,"abstract":"<p><strong>Background: </strong>Family history (FH) of cancer is an established risk factor for early onset of cancer. However, reliable estimates on the difference in onset age between familial and sporadic cancers remain scarce in the Chinese population.</p><p><strong>Methods: </strong>This multicenter, hospital-based, cross-sectional study included 23 hospitals across 12 provinces. Patients diagnosed with cancers of the lung, stomach, esophagus, or colorectum between January 1, 2016 and December 31, 2017 were identified. Detailed information on sociodemographic characteristics, lifestyle factors, stage at diagnosis, and onset age was collected. We analyzed the association between FH and onset age across different cancer types using quantile regressions, and the potential bias was explored.</p><p><strong>Results: </strong>Among 41,072 eligible patients, 3054 (7.44%) reported a first-degree FH of cancer, and they were diagnosed at younger ages than those without FH (median difference: -1.19, 95% confidence interval [CI]: -1.59 to -0.79). Stratified by cancer type, the most pronounced difference was observed in colorectal cancer (median difference: -2.25, 95% CI: -3.31 to -1.19). Failure to account for lead time bias resulted in an overestimation of the FH effect, ranging from 3.4% to 15.4% across cancer types. Quantile regression analysis revealed that the impact of FH on age at diagnosis was more pronounced at the upper tail of the age distribution for all cancers combined and for each cancer type individually.</p><p><strong>Conclusions: </strong>Our findings suggest that FH of cancer is associated with the early onset of lung, stomach, esophageal, and colorectal cancers in China. Cancer screening at earlier ages is needed for individuals with an FH.</p>","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233318","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}
{"title":"Urban-rural disparities in mortality due to stroke subtypes in China and its provinces, 2015-2020.","authors":"Yi Ren, Jia Yang, Peng Yin, Wei Liu, Zheng Long, Chen Zhang, Zixin Wang, Haijie Liu, Maigeng Zhou, Qingfeng Ma, Junwei Hao","doi":"10.1097/CM9.0000000000003135","DOIUrl":"10.1097/CM9.0000000000003135","url":null,"abstract":"<p><strong>Background: </strong>Death burden of stroke is severe with over one-third rural residents in China, but there is still a lack of specific national and high-quality reports on the urban-rural differences in stroke burden, especially for subtypes. We aimed to update the understanding of urban-rural differences in stroke deaths.</p><p><strong>Methods: </strong>This is a descriptive observational study. Data from the national mortality surveillance system, which covers 323.8 million with 605 disease surveillance points (DSPs) across all 31 provinces, municipalities, and autonomous regions in China. All deaths from stroke as the underlying cause from 2015 to 2020 according to DSPs. Crude mortality rate and age-standardized mortality rate (ASMR) were estimated through DSPs. Average annual percentage change was used to explain the change in mortality rate.</p><p><strong>Results: </strong>From 2015 to 2020, the majority of deaths from all stroke subtypes occurred in rural areas. There were significant differences between the changes of urban and rural ASMRs. On the whole, the changes in urban areas were evidently better, and the ASMR differences were basically expanding. Stroke ASMR in urban China decreased by 15.5%. The rural ASMR of ischemic stroke increased by 12.9%. The rural and urban ASMRs of intracerebral hemorrhage decreased by 24.9% and 27.4%, and those of subarachnoid hemorrhage decreased by 29.5% and 40.4%, respectively. The highest ASMRs of all stroke subtypes and the increasing trend of ischemic stroke ASMR make rural males the focus of stroke management.</p><p><strong>Conclusions: </strong>The death burden of stroke varies greatly between urban and rural China. Rural residents face unique challenges.</p>","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":"1345-1354"},"PeriodicalIF":7.5,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342701","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}
Chinese Medical JournalPub Date : 2025-06-05Epub Date: 2024-09-30DOI: 10.1097/CM9.0000000000003173
Zhikai Liao, Yunzhu Yao, Bingqi Dong, Yue Le, Longfei Luo, Fang Miao, Shan Jiang, Tiechi Lei
{"title":"Involvement of interferon γ-producing mast cells in immune responses against melanocytes in vitiligo requires Mas-related G protein-coupled receptor X2 activation.","authors":"Zhikai Liao, Yunzhu Yao, Bingqi Dong, Yue Le, Longfei Luo, Fang Miao, Shan Jiang, Tiechi Lei","doi":"10.1097/CM9.0000000000003173","DOIUrl":"10.1097/CM9.0000000000003173","url":null,"abstract":"<p><strong>Background: </strong>Increasing evidence indicates that oxidative stress and interferon γ (IFNγ)-driven cellular immune responses are responsible for the pathogenesis of vitiligo. However, the connection between oxidative stress and the local production of IFNγ in early vitiligo remains unexplored. The aim of this study was to identify the mechanism underlying the production of IFNγ by mast cells and its impact on vitiligo pathogenesis.</p><p><strong>Methods: </strong>Skin specimens from the central, marginal, and perilesional skin areas of active vitiligo lesions were collected to characterize changes of mast cells, CD8 + T cells, and IFNγ-producing cells. Cell supernatants from hydrogen peroxide (H 2 O 2 )-treated keratinocytes (KCs) were harvested to measure levels of soluble stem cell factor (sSCF) and matrix metalloproteinase (MMP)-9. A murine vitiligo model was established using Mas-related G protein-coupled receptor-B2 (MrgB2, mouse ortholog of human MrgX2) conditional knockout (MrgB2 -/- ) mice to investigate IFNγ production and inflammatory cell infiltrations in tail skin following the challenge with tyrosinase-related protein (Tyrp)-2 180 peptide. Potential interactions between the Tyrp-2 180 peptide and MrgX2 were predicted using molecular docking. The siRNAs targeting MrgX2 and the calcineurin inhibitor FK506 were also used to examine the signaling pathways involved in mast cell activation.</p><p><strong>Results: </strong>IFNγ-producing mast cells were closely aligned with the recruitment of CD8 + T cells in the early phase of vitiligo skin. sSCF released by KCs through stress-enhanced MMP9-dependent proteolytic cleavage recruited mast cells into sites of inflamed skin (Perilesion vs . lesion, 13.00 ± 4.00/high-power fields [HPF] vs . 26.60 ± 5.72/HPF, P <0.05). Moreover, IFNγ-producing mast cells were also observed in mouse tail skin following challenge with Tyrp-2 180 (0 h vs . 48 h post-recall, 0/HPF vs . 3.80 ± 1.92/HPF, P <0.05). The IFNγ + mast cell and CD8 + T cell counts were lower in the skin of MrgB2 -/- mice than in those of wild-type mice (WT vs . KO 48 h post-recall, 4.20 ± 0.84/HPF vs . 0.80 ± 0.84/HPF, P <0.05).</p><p><strong>Conclusion: </strong>Mast cells activated by MrgX2 serve as a local IFNγ producer that bridges between innate and adaptive immune responses against MCs in early vitiligo. Targeting MrgX2-mediated mast cell activation may represent a new strategy for treating vitiligo.</p>","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":"1367-1378"},"PeriodicalIF":7.5,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342691","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}
Chinese Medical JournalPub Date : 2025-06-05Epub Date: 2025-03-17DOI: 10.1097/CM9.0000000000003574
Fei Han, Siyuan Fan, Bo Hou, Lixin Zhou, Ming Yao, Min Shen, Yicheng Zhu, Joanna M Wardlaw, Jun Ni
{"title":"Inflammatory disorders that affect the cerebral small vessels.","authors":"Fei Han, Siyuan Fan, Bo Hou, Lixin Zhou, Ming Yao, Min Shen, Yicheng Zhu, Joanna M Wardlaw, Jun Ni","doi":"10.1097/CM9.0000000000003574","DOIUrl":"10.1097/CM9.0000000000003574","url":null,"abstract":"<p><strong>Abstract: </strong>This comprehensive review synthesizes the latest advancements in understanding inflammatory disorders affecting cerebral small vessels, a distinct yet understudied category within cerebral small vessel diseases (SVD). Unlike classical SVD, these inflammatory conditions exhibit unique clinical presentations, imaging patterns, and pathophysiological mechanisms, posing significant diagnostic and therapeutic challenges. Highlighting their heterogeneity, this review spans primary angiitis of the central nervous system, cerebral amyloid angiopathy-related inflammation, systemic vasculitis, secondary vasculitis, and vasculitis in autoinflammatory diseases. Key discussions focus on emerging insights into immune-mediated processes, neuroimaging characteristics, and histopathological distinctions. Furthermore, this review underscores the importance of standardized diagnostic frameworks, individualized immunomodulation approaches, and novel targeted therapies to address unmet clinical demands.</p>","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":"1301-1312"},"PeriodicalIF":7.5,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647340","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}
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