Precision Clinical Medicine最新文献

{"title":"SKP2 at the crossroads of proliferation and immune evasion: a new target in the tumor microenvironment.","authors":"Panagiotis J Vlachostergios, Stergios Boussios","doi":"10.1093/pcmedi/pbaf033","DOIUrl":"10.1093/pcmedi/pbaf033","url":null,"abstract":"","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"8 4","pages":"pbaf033"},"PeriodicalIF":6.4,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12673205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145678864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Randomized controlled clinical trial of Shenzhuo Formula in the treatment of macroalbuminuria in diabetic kidney disease and its inflammation-modulating mechanisms.","authors":"Anzhu Wang, Yishan Huang, Yu Wei, Lili Zhang, Hongdong Chen, Xiaoqing Wang, Zhimei Cui, Bin Wang, Wei Liu, Chao Chen, Ye Lei, Zhonghua Zheng, Yan Wei, Jia Mi, Keda Lu, Ying Zhang, Xiaolin Tong, Linhua Zhao","doi":"10.1093/pcmedi/pbaf031","DOIUrl":"10.1093/pcmedi/pbaf031","url":null,"abstract":"<p><strong>Background: </strong>Shenzhuo Formula (SZF), a modified Didang Tang, is used for diabetic kidney disease (DKD), though high-quality evidence is limited.</p><p><strong>Methods: </strong>In a randomized, double-blind, double-dummy, active-controlled, multicenter trial, irbesartan (IRB) was the control. A Bayesian model assessed efficacy. Mechanistic studies included Olink inflammation proteomics, single-cell RNA sequencing (scRNA-seq) of KK-Ay mouse kidneys, and <i>in vivo</i> experiments.</p><p><strong>Results: </strong>A total of 120 DKD patients with macroalbuminuria were randomized (SZF <i>n</i> = 57, IRB <i>n</i> = 63). At 24 weeks, 24 h urinary total protein change was -0.03 (-0.24 to 0.18) g/24 h in the SZF group and 0.08 (-0.30 to 0.14) g/24 h in the IRB group (<i>P</i> = 0.61). Estimated glomerular filtration rate improved with SZF by 5.91 (1.80 to 10.01) mL/min/1.73m² but declined with IRB by -1.67 (-5.18 to 1.84) mL/min/1.73m² (<i>P</i> < 0.01). Serum creatinine decreased with SZF by -5.15 (-9.73 to -0.56) μmol/L but increased with IRB by 3.39 (-0.84 to 7.61) μmol/L (<i>P</i> < 0.01). Traditional Chinese medicine syndrome response was higher with SZF (89.47% vs. 63.49%, <i>P</i> < 0.01). Safety and metabolic parameters were comparable. Bayesian analysis favored SZF for renal benefit. Mechanistically, SZF downregulated CX3CL1 in endothelial cells and MCP-1 in mesangial and tubular cells, suggesting anti-inflammatory effects restoring endothelial function and attenuating fibrosis.</p><p><strong>Conclusions: </strong>SZF matched IRB in proteinuria reduction but was superior in preserving renal function and improving traditional Chinese medicine symptoms in DKD, with good safety. Benefits may involve suppression of CX3CL1/MCP-1-mediated inflammation.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"8 4","pages":"pbaf031"},"PeriodicalIF":5.0,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12699223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145757870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endocrinologist at a crossroads: professional obsolescence challenged by artificial intelligence.","authors":"Xuelian Xiong","doi":"10.1093/pcmedi/pbaf029","DOIUrl":"10.1093/pcmedi/pbaf029","url":null,"abstract":"","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"8 4","pages":"pbaf029"},"PeriodicalIF":5.0,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12690195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145744857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The irreplaceable role of pathology for the clinical translation of patient-derived organoids in precision medicine.","authors":"Zuoyu Liang, Ping Yang, Xinglong Zhu, Yihong Liu, Mumin Shao, Zaiyu Yang, Ji Bao","doi":"10.1093/pcmedi/pbaf032","DOIUrl":"10.1093/pcmedi/pbaf032","url":null,"abstract":"","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"8 4","pages":"pbaf032"},"PeriodicalIF":5.0,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12699221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145757797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-diabetic medications and cancer: links beyond glycemic and body weight control.","authors":"Meng Cao, Chu Lin, Xiaoling Cai, Fang Lv, Wenjia Yang, Linong Ji","doi":"10.1093/pcmedi/pbaf028","DOIUrl":"10.1093/pcmedi/pbaf028","url":null,"abstract":"<p><p>Cancer is becoming one of the leading causes of death among patients with diabetes. Hyperglycemia and obesity, two key characteristics of type 2 diabetes, modify the risks of cancer in patients with type 2 diabetes. However, recent studies suggested that glycemic control and weight loss mediated by anti-diabetic medications might not be sufficient to lower the risks of cancer in patients with type 2 diabetes. Thus, there is a need to explore the association between anti-diabetic medications and cancer beyond glycemic and body weight control. This review has summarized the preclinical and clinical evidence between various anti-diabetic drugs and cancer. More importantly, this review focused on the underlying links between anti-diabetic medications and cancer beyond glycemic and body weight control, including modified cell proliferation, altered levels of some hormones, inflammation and oxidative stimuli, autophagy and apoptosis, intestinal flora shift, and angiogenesis and epithelial-mesenchymal transition. This review may provide insights for future clinical and mechanistic studies to further elucidate the association between anti-diabetic medications and cancer.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"8 4","pages":"pbaf028"},"PeriodicalIF":5.0,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12690206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145744859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The recurrence or metastasis related gene predicts the prognosis of extremity and trunk soft tissue sarcoma.","authors":"Duo Wang, Dawei Sun, Jihao Tu, Xingyao Cui, Limei Qu, Lei Chen, Zhixin Zhang, Ziping Jiang, Ruijun Li, Zhaopeng Xuan, Jianli Cui, Xiguang Sun, Xiaoyan Jia, Pengcheng Liu, Ying Xiong, Jianing Wang, Yanfang Jiang, Bin Liu","doi":"10.1093/pcmedi/pbaf027","DOIUrl":"10.1093/pcmedi/pbaf027","url":null,"abstract":"<p><strong>Background: </strong>Relapsed soft tissue sarcomas (STS) have poor prognosis and limited treatment options. However, the molecular mechanism underlying recurrence and the prognostic predictor for STS are unclear.</p><p><strong>Methods: </strong>We enrolled 35 extremity and trunk STS patients. Tumor specimens of 20 relapsed and 15 primary STS underwent sequencing to detect DNA mutation, RNA expression, and DNA methylation. Moreover, 206 STS cases from The Cancer Genome Atlas (TCGA) were utilized to construct the relapse-associated risk score model (RRSM), validated using three Gene Expression Omnibus datasets. Key model genes, COL6A3, FZD7, ITPKA, and PRKAG1, were validated in formalin-fixed paraffin-embedded tissue sections from primary and relapsed STS patients, confirming their potential involvement in STS recurrence.</p><p><strong>Results: </strong>The primary STS exhibited an immune-enriched tumor microenvironment, whereas the tumor microenvironment of relapsed STS had features that promote tumor recurrence or metastasis. The RRSM could predict relapse-free survival in TCGA STS and performed well in the validation cohort. Multivariate analysis revealed that RRSM was an independent prognostic factor. Moreover, the nomogram developed had excellent predictive ability.</p><p><strong>Conclusions: </strong>This study revealed different multi-omic profiles between relapsed and primary STS. RRSM is a potential prognostic predictor for STS and lays a foundation for early intervention of high-risk STS patients. The expression of genes FZD7, ITPKA, and PRKAG1 may guide STS treatment decisions.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"8 4","pages":"pbaf027"},"PeriodicalIF":5.0,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12793454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145966844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic regulation of T cell production of IL-10 and IL-22 protects against intestinal inflammation.","authors":"Han Liu, Xiaojing Zhao, Tianming Yu, Yu Yu, Suxia Yao, Wenjing Yang, Yingzi Cong","doi":"10.1093/pcmedi/pbaf025","DOIUrl":"10.1093/pcmedi/pbaf025","url":null,"abstract":"<p><strong>Objectives: </strong>Inflammatory bowel disease is driven by dysregulated CD4⁺ T cell responses to the intestinal microbiota. While T cells can exacerbate inflammation by producing proinflammatory cytokines, they also produce anti-inflammatory mediators, such as interleukin 10 (IL-10) and IL-22. However, the metabolic programs that regulate IL-10 and IL-22 production remain incompletely defined.</p><p><strong>Methods: </strong>We used CBir1 transgenic mice and <i>in vitro</i> Th1 polarization assays to investigate how metabolic pathways regulate T cell production of IL-10 and IL-22. A panel of metabolic inhibitors was tested for their effects on cytokine expression. Transcriptional mechanisms were assessed using bulk RNA sequencing, qPCR, Enzyme-linked immunosorbent (ELISA), and CRISPR-Cas9-mediated gene editing. Functional relevance was validated using <i>Citrobacter rodentium</i> infection and T cell suppression assays <i>in vivo</i> and <i>in vitro</i>.</p><p><strong>Results: </strong>Among tested metabolic inhibitors, dichloroacetate (DCA) significantly enhanced IL-10 and IL-22 production by CD4⁺ T cells. DCA increased maximal oxygen consumption and decreased lactate secretion in T cells. Mechanistically, DCA upregulated aryl hydrocarbon receptor (<i>Ahr</i>) and downregulated <i>Bhlhe40</i>, without affecting <i>Prdm1</i>. Pharmacologic inhibition of Ahr suppressed DCA-induced IL-22, but not IL-10, while Bhlhe40 knockout enhanced IL-10 production, identifying distinct transcriptional regulators for each cytokine. Functionally, DCA-treated Th1 cells suppressed naïve T cell proliferation via IL-10. In an <i>in vivo</i> experiment, DCA treatment protected mice from <i>C. rodentium-</i>induced colitis.</p><p><strong>Conclusions: </strong>Our findings demonstrate that DCA enhances IL-22 and IL-10 production in Th1 cells through Ahr and Bhlhe40, respectively. These results identify a novel metabolic mechanism by which DCA promotes mucosal immune regulation and highlight its potential as a therapeutic strategy for inflammatory bowel disease.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"8 4","pages":"pbaf025"},"PeriodicalIF":5.0,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12658364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145649453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell transcriptomic profiling reveals distinct tumor microenvironments in HPV-associated penile squamous cell carcinoma.","authors":"Lianbang Zhu, Deyun Shen, Jiahao Zhou, Chen Cheng, Zhiyao Xu, Yong Liang, Wen Pan, Tao Tao","doi":"10.1093/pcmedi/pbaf013","DOIUrl":"10.1093/pcmedi/pbaf013","url":null,"abstract":"<p><strong>Background: </strong>Penile squamous cell carcinoma (PSCC) is a rare yet potentially lethal malignancy, often resulting in devastating disfigurement, with a 5-year survival rate of only ∼50%. Human papillomavirus (HPV) infection is implicated in approximately half of PSCC cases and is associated with improved clinical outcomes; however, the underlying mechanisms remain poorly understood.</p><p><strong>Methods: </strong>To elucidate HPV-associated differences in the tumor microenvironment, we performed single-cell RNA sequencing on tumors from 11 treatment-naïve PSCC patients, analyzing a total of 52 980 single cells. Unsupervised clustering identified 49 distinct cellular clusters across immune and stromal compartments.</p><p><strong>Results: </strong>HPV-positive tumors exhibited an increased abundance of mast cells and a reduction in the proliferative macrophages subpopulation compared to HPV-negative tumors. Notably, CD8⁺ T cells in HPV-positive PSCC expressed lower levels of immune checkpoint molecules, suggesting a less exhausted immune state. Conversely, TIGIT and its ligands were significantly enriched in HPV-negative tumors, potentially fostering an immunosuppressive niche.</p><p><strong>Conclusion: </strong>Collectively, our study delineates the single-cell landscape of PSCC and highlights distinct tumor microenvironment remodeling associated with HPV status, suggesting that the reduced immunosuppression in HPV-positive tumors may underlie their more favorable prognosis.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"8 3","pages":"pbaf013"},"PeriodicalIF":5.0,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12421235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145041681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bile acid metabolism and hepatocellular carcinoma: mechanisms of drug resistance and intervention strategies.","authors":"Yan Lu, Xiaochen Feng, Zhijie Wang, Minghao Zou, Zheqi Xu, Qianjia Liu, Wenjin Chen, Jin Ding, Hui Liu","doi":"10.1093/pcmedi/pbaf020","DOIUrl":"10.1093/pcmedi/pbaf020","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is the predominant malignant liver tumor, characterized by high morbidity, mortality, and rapid progression, and it ranks among the leading causes of cancer-related fatalities worldwide. Its treatment is facing the severe challenge of resistance to targeted drugs and immunotherapy. Bile acids (BAs) are products of cholesterol metabolism, that not only regulate lipid digestion and absorption, but also influence the development of HCC by modulating inflammation and metabolism. Dysregulation of BA metabolism is closely linked to resistance against targeted therapies and immunotherapies. BAs reduce the efficacy of targeted drugs by influencing enzymes involved in drug metabolism and drug efflux transporters, moreover, BAs also lead to immunotherapeutic resistance by regulating the formation of the immunosuppressive tumor microenvironment. Therefore, regulating BA metabolism has the potential to overcome drug resistance of targeted therapy and immunotherapy, which could be a promising treatment strategy. This review not only summarizes the roles of BA metabolism in HCC development and drug resistance, but also further explores the rationality and necessity of targeting BAs to enhance the survival of HCC patients.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"8 3","pages":"pbaf020"},"PeriodicalIF":6.4,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145114378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mechanisms and genetic features of cholangiocarcinoma: implications for targeted therapeutic strategies.","authors":"Xiao Lu, Shoujia Xu, Zhe Deng, Min-Jun Wang, Fei Chen","doi":"10.1093/pcmedi/pbaf021","DOIUrl":"10.1093/pcmedi/pbaf021","url":null,"abstract":"<p><p>Cholangiocarcinoma (CCA) is a biologically diverse and highly aggressive cancer that arises from the biliary epithelium. It is typically divided into intrahepatic, perihilar, and distal types, each with distinct clinical behavior, genetic alterations, and therapeutic responses. Worldwide, the global incidence of CCA has risen steadily, accounting for nearly 15% of liver cancers and ∼3% of all gastrointestinal malignancies. CCA often presents at an advanced stage due to its silent onset and shows poor responsiveness to conventional chemotherapy, resulting in high mortality, accounting for ∼2% of cancer-related deaths worldwide. Risk factors include parasitic infections like liver flukes and chronic biliary diseases such as cholelithiasis and primary sclerosing cholangitis, although most cases have unknown origins. While early-stage patients may benefit from surgical resection or liver transplantation, these options are often not viable in advanced disease due to high relapse rates. In cases of unresectable or metastatic CCA, treatment remains difficult due to resistance and a lack of effective targeted therapies. This review systematically integrates the genomic, epigenetic, and signaling network mechanisms underlying CCA with their translational implications, providing a critical synthesis of the rapidly evolving field of targeted therapies, including recently approved Food and Drug Administration treatments and emerging novel agents. We specifically emphasize the key mechanisms of therapeutic resistance and corresponding strategies to overcome them, present an updated evaluation of vulnerabilities across distinct molecular subgroups, and explore the major challenges and future trajectories for advancing biomarker-driven precision medicine in CCA, thereby offering a forward-looking and clinically relevant perspective.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"8 3","pages":"pbaf021"},"PeriodicalIF":5.0,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145114337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}