Chinese Medical Journal最新文献

{"title":"Novel paradigms in KRAS targeting: Unveiling strategies to combat drug resistance.","authors":"Xiyuan Luo, Feihan Zhou, Yuemeng Tang, Xiaohong Liu, Ruilin Xiao, Minzhi Gu, Jialu Bai, Decheng Jiang, Gang Yang, Lei You, Yupei Zhao","doi":"10.1097/CM9.0000000000003776","DOIUrl":"10.1097/CM9.0000000000003776","url":null,"abstract":"<p><strong>Abstract: </strong>The Kirsten rat sarcoma viral oncogene homolog ( KRAS ) mutation is one of the most prevalent activating alterations in cancer. It indicates a poor overall prognosis due to its highly invasive nature. Although several KRAS inhibitors have been developed in recent years, a significant clinical challenge has emerged as a substantial proportion of patients eventually develop resistance to these therapies. Therefore, identifying determinants of drug resistance is critical for guiding treatment strategies. This review provides a comprehensive overview of the mutation landscape and molecular mechanisms of KRAS activity in various cancers. Meanwhile, it summaries the progress and prospects of small molecule KRAS inhibitors undergoing clinical trials. Furthemore, this review explores potential strategies to overcome drug resistance, with the ultimate goal of steering toward patient-centric precision oncology in the foreseeable future.</p>","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":"2243-2267"},"PeriodicalIF":7.3,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12453332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma exchange and intravenous immunoglobulin prolonged the survival of a porcine kidney xenograft in a sensitized, brain-dead human recipient.","authors":"Shuaijun Ma, Ruochen Qi, Shichao Han, Zhengxuan Li, Xiaoyan Zhang, Guohui Wang, Kepu Liu, Tong Xu, Yang Zhang, Donghui Han, Jingliang Zhang, Di Wei, Xiaozheng Fan, Dengke Pan, Yanyan Jia, Jing Li, Zhe Wang, Xuan Zhang, Zhaoxu Yang, Kaishan Tao, Xiaojian Yang, Kefeng Dou, Weijun Qin","doi":"10.1097/CM9.0000000000003338","DOIUrl":"10.1097/CM9.0000000000003338","url":null,"abstract":"<p><strong>Background: </strong>The primary limitation to kidney transplantation is organ shortage. Recent progress in gene editing and immunosuppressive regimens has made xenotransplantation with porcine organs a possibility. However, evidence in pig-to-human xenotransplantation remains scarce, and antibody-mediated rejection (AMR) is a major obstacle to clinical applications of xenotransplantation.</p><p><strong>Methods: </strong>We conducted a kidney xenotransplantation in a brain-dead human recipient using a porcine kidney with five gene edits (5GE) on March 25, 2024 at Xijing Hospital, China. Clinical-grade immunosuppressive regimens were employed, and the observation period lasted 22 days. We collected and analyzed the xenograft function, ultrasound findings, sequential protocol biopsies, and immune surveillance of the recipient during the observation.</p><p><strong>Results: </strong>The combination of 5GE in the porcine kidney and clinical-grade immunosuppressive regimens prevented hyperacute rejection. The xenograft kidney underwent delayed graft function in the first week, but urine output increased later and the single xenograft kidney maintained electrolyte and pH homeostasis from postoperative day (POD) 12 to 19. We observed AMR at 24 h post-transplantation, due to the presence of pre-existing anti-porcine antibodies and cytotoxicity before transplantation; this AMR persisted throughout the observation period. Plasma exchange and intravenous immunoglobulin treatment mitigated the AMR. We observed activation of latent porcine cytomegalovirus toward the end of the study, which might have contributed to coagulation disorder in the recipient.</p><p><strong>Conclusions: </strong>5GE and clinical-grade immunosuppressive regimens were sufficient to prevent hyperacute rejection during pig-to-human kidney xenotransplantation. Pre-existing anti-porcine antibodies predisposed the xenograft to AMR. Plasma exchange and intravenous immunoglobulin were safe and effective in the treatment of AMR after kidney xenotransplantation.</p>","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":"2293-2307"},"PeriodicalIF":7.3,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12453306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut: The gate and key to brain.","authors":"Xiaohan Zhang, Yunsheng Yang","doi":"10.1097/CM9.0000000000003767","DOIUrl":"10.1097/CM9.0000000000003767","url":null,"abstract":"<p><strong>Abstract: </strong>Brain science is the frontier of modern science, and new advances have been made in brain-like designs and brain-computer interfaces to simulate or develop brain functions. However, given that the brain is hermetically sealed within the skull, exploration and deciphering of the brain structure and functions are limited. Growing evidence suggests that the gut is not just a digestive organ. It not only provides essential nutrients and electrolytes for brain neurodevelopment and the maintenance of brain function, but it also transmits external environmental and intestinal wall signals from the intestinal lumen to the central nervous system through multiple pathways to regulate brain activity, function, and structure. A variety of gut-brain interaction pathways have been identified, including neural pathways, neuroimmune signaling, endocrine pathways, and biochemical messengers produced by gut microbes. Gut microbes interact with food and the gut to modulate gut-brain communication. The gut's important role and potential in neurodevelopment, maintenance of normal function, and disease development make it an increasingly important area of research in brain science and neuropsychiatric disorders. The gut's unique role in brain functions and its accessibility for research (compared to direct brain studies) establish it as a critical gate to understanding the mysteries of brain science. Crucially, intestinal nutrients and microbes provide two unique keys to unlock this gate-enabling neural regulation and novel treatments for neuropsychiatric diseases.</p>","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":"2207-2219"},"PeriodicalIF":7.3,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12453317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral microbiome between patients with non-obstructive and obstructive hypertrophic cardiomyopathy.","authors":"Qianyi Qin, Yuming Zhu, Liu Yang, Runzhi Guo, Lei Song, Dong Wang, Weiran Li","doi":"10.1097/CM9.0000000000003777","DOIUrl":"10.1097/CM9.0000000000003777","url":null,"abstract":"<p><strong>Background: </strong>The profile and clinical significance of the oral microbiome in patients with non-obstructive hypertrophic cardiomyopathy (noHCM) and obstructive hypertrophic cardiomyopathy (oHCM) remain unexplored. The objective of this study was to evaluate the difference of oral microbiome between noHCM and oHCM patients.</p><p><strong>Methods: </strong>This cross-sectional study enrolled 18 noHCM patients and 26 oHCM patients from Fuwai Hospital, Chinese Academy of Medical Sciences between 2020 and 2021. Clinical and periodontal evaluations were conducted, and subgingival plaque samples were collected. Metagenomic sequencing and subsequent microbial composition and functional analyses were performed.</p><p><strong>Results: </strong>Compared to oHCM patients, those with noHCM had higher systolic blood pressure (138.1 ± 18.8 mmHg vs . 124.2 ± 13.8 mmHg, P = 0.007), a larger body circumference (neck circumference: 39.2 ± 4.0 cm vs . 35.1 ± 3.7 cm, P = 0.001; waist circumference: 99.7 ± 10.5 cm vs . 92.2 ± 10.8 cm, P = 0.027; hip circumference: 102.5 ± 5.6 cm vs . 97.5 ± 9.1 cm, P = 0.030), a greater left ventricular end-diastolic diameter (46.6 ± 4.9 mm vs . 43.1 ± 4.9 mm, P = 0.026), and a lower left ventricular ejection fraction (64.1 ± 5.7 % vs . 68.5 ± 7.8%, P = 0.048). While overall biodiversity and general microbial composition were similar between the noHCM and oHCM groups, ten taxa displayed significant differences at the genus and species levels, with Porphyromonas gingivalis showing the highest abundance and greater enrichment in noHCM (relative abundance: 7.79535 vs . 4.87697, P = 0.043). Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis identified ten distinct pathways, with pathways related to energy and amino acid metabolism being enriched in oHCM patients, and those associated with genetic information processing less abundant in the oHCM group. Metabolic potential analysis revealed ten significantly altered metabolites primarily associated with amino sugar and nucleotide sugar metabolism, porphyrin metabolism, pentose and glucuronate interconversion, and lysine degradation.</p><p><strong>Conclusions: </strong>The higher abundance of Porphyromonas gingivalis , which is known to impact cardiovascular health, in noHCM patients may partially account for clinical differences between the groups. Pathway enrichment and metabolic potential analyses suggest microbial functional shifts between noHCM and oHCM patients, potentially reflecting inherent metabolic changes in HCM.</p>","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":"2308-2315"},"PeriodicalIF":7.3,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12453338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ZQL-4c exerts anti-tumor effects by specifically targeting SCD1 in triple-negative breast cancer both in vitro and in vivo.","authors":"Xiaorui Li, Hui Cao, Hongna Sun, Shuya Wang, Xiangyu Guo, Shisheng Wang, Tao Sun","doi":"10.1097/CM9.0000000000003604","DOIUrl":"10.1097/CM9.0000000000003604","url":null,"abstract":"","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":"2359-2361"},"PeriodicalIF":7.3,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12453352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chest computed tomography-based artificial intelligence-aided latent class analysis for diagnosis of severe pneumonia.","authors":"Caiting Chu, Yiran Guo, Zhenghai Lu, Ting Gui, Shuhui Zhao, Xuee Cui, Siwei Lu, Meijiao Jiang, Wenhua Li, Chengjin Gao","doi":"10.1097/CM9.0000000000003226","DOIUrl":"10.1097/CM9.0000000000003226","url":null,"abstract":"<p><strong>Background: </strong>There is little literature describing the artificial intelligence (AI)-aided diagnosis of severe pneumonia (SP) subphenotypes and the association of the subphenotypes with the ventilatory treatment efficacy. The aim of our study is to illustrate whether clinical and biological heterogeneity, such as ventilation and gas-exchange, exists among patients with SP using chest computed tomography (CT)-based AI-aided latent class analysis (LCA).</p><p><strong>Methods: </strong>This retrospective study included 413 patients hospitalized at Xinhua Hospital diagnosed with SP from June 1, 2015 to May 30, 2020. AI quantification results of chest CT and their combination with additional clinical variables were used to develop LCA models in an SP population. The optimal subphenotypes were determined though evaluating statistical indicators of all the LCA models, and clinical implications of them such as guiding ventilation strategies were further explored by statistical methods.</p><p><strong>Results: </strong>The two-class LCA model based on AI quantification results of chest CT can describe the biological characteristics of the SP population well and hence yielded the two clinical subphenotypes. Patients with subphenotype-1 had milder infections ( P <0.001) than patients with subphenotype-2 and had lower 30-day ( P <0.001) and 90-day ( P <0.001) mortality, and lower in-hospital ( P = 0.001) and 2-year ( P <0.001) mortality. Patients with subphenotype-1 showed a better match between the percentage of non-infected lung volume (used to quantify ventilation) and oxygen saturation (used to reflect gas exchange), compared with patients with subphenotype-2. There were significant differences in the matching degree of lung ventilation and gas exchange between the two subphenotypes ( P <0.001). Compared with patients with subphenotype-2, those with subphenotype-1 showed a relatively better match between CT-based AI metrics of the non-infected region and oxygenation, and their clinical outcomes were effectively improved after receiving invasive ventilation treatment.</p><p><strong>Conclusions: </strong>A two-class LCA model based on AI quantification results of chest CT in the SP population particularly revealed clinical heterogeneity of lung function. Identifying the degree of match between ventilation and gas-exchange may help guide decisions about assisted ventilation.</p>","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":"2316-2323"},"PeriodicalIF":7.3,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12453313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142580994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Off-the-shelf human umbilical cord mesenchymal stromal cell product in acute-on-chronic liver failure: A multicenter phase I/II clinical trial.","authors":"Lina Cui, Huaibin Zou, Shaoli You, Changcun Guo, Jundong Gu, Yulong Shang, Gui Jia, Linhua Zheng, Juan Deng, Xiufang Wang, Ruiqing Sun, Dawei Ding, Weijie Wang, Xia Zhou, Guanya Guo, Yansheng Liu, Zhongchao Han, Zhibo Han, Yu Chen, Ying Han","doi":"10.1097/CM9.0000000000003768","DOIUrl":"10.1097/CM9.0000000000003768","url":null,"abstract":"","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":"2347-2349"},"PeriodicalIF":7.3,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12453329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low handgrip strength as a potential indicator of 2-year mortality in older Chinese inpatients: A multicenter prospective cohort study.","authors":"Miao Yu, Jing Jiao, Feilong Chen, Jiaqi Ding, Xinjuan Wu, Tao Xu","doi":"10.1097/CM9.0000000000003597","DOIUrl":"10.1097/CM9.0000000000003597","url":null,"abstract":"","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":"2353-2355"},"PeriodicalIF":7.3,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12453345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utility of upper urinary tract video urodynamics in recurrent symptoms and equivocal hydronephrosis after ureteral reconstruction: A retrospective cohort study.","authors":"Xinfei Li, Yiming Zhang, Liqing Xu, Chen Huang, Zhihua Li, Kunlin Yang, Hua Guan, Jing Liu, Peng Zhang, Hongjian Zhu, Liqun Zhou, Xuesong Li","doi":"10.1097/CM9.0000000000003755","DOIUrl":"10.1097/CM9.0000000000003755","url":null,"abstract":"","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":"2350-2352"},"PeriodicalIF":7.3,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12453369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long non-coding RNA PVT1 mediates bile acid-induced gastric intestinal metaplasia via a miR-34b-5p/HNF4α positive feedback loop.","authors":"Kexin Lin, Nuo Yao, Xingyu Zhao, Xiaodong Qu, Xuezhi Li, Songbo Li, Shiyue Luo, Min Chen, Na Wang, Yongquan Shi","doi":"10.1097/CM9.0000000000003621","DOIUrl":"10.1097/CM9.0000000000003621","url":null,"abstract":"<p><strong>Background: </strong>Bile acids (BAs) facilitate the progression of gastric intestinal metaplasia (GIM). Long non-coding RNAs (lncRNAs) dysregulation was observed along with the initiation of gastric cancer. However, how lncRNAs function in GIM remains unclear. This study aimed to explore the role and mechanism of lncRNA PVT1 in GIM, and provide a potential therapeutic target for GIM treatment.</p><p><strong>Methods: </strong>We employed RNA sequencing (RNA-seq) to screen dysregulated lncRNAs in gastric epithelial cells after BA treatment. Bioinformatics analysis was conducted to reveal the regulatory mechanism. PVT1 expression was detected in 21 paired biopsies obtained under endoscopy. Overexpressed and knockdown cell models were established to explore gene functions in GIM. Molecular interactions were validated by dual-luciferase reporter assay, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (Ch-IP). The levels of relative molecular expression were detected in GIM tissues.</p><p><strong>Results: </strong>We confirmed that lncRNA PVT1 was upregulated in BA-induced GIM model. PVT1 promoted the expression of intestinal markers such as CDX2 , KLF4 , and HNF4α . Bioinformatics analysis revealed that miR-34b-5p was a putative target of PVT1 . miR-34b-5p mimics increased CDX2 , KLF4 , and HNF4α levels. Restoration of miR-34b-5p decreased the pro-metaplastic effect of PVT1 . The interactions between PVT1 , miR-34b-5p, and the downstream target HNF4α were validated. Moreover, HNF4α could transcriptionally activated PVT1 , sustaining the GIM phenotype. Finally, the activation of the PVT1 /miR-34b-5p/ HNF4α loop was detected in GIM tissues.</p><p><strong>Conclusions: </strong>BAs facilitate GIM partially via a PVT1/miR-34b-5p/HNF4α positive feedback loop. PVT1 may become a novel target for blocking the continuous development of GIM and preventing the initiation of gastric cancer in patients with bile reflux.</p>","PeriodicalId":10183,"journal":{"name":"Chinese Medical Journal","volume":" ","pages":"2324-2335"},"PeriodicalIF":7.3,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12453363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}