Precision Clinical Medicine最新文献

{"title":"Therapeutic strategy for cervical gastric-type adenocarcinoma by targeting CLU to relieve CLU-associated stress and sensitize chemotherapy.","authors":"Tong Wu, Xinyu Qu, Lili Jiang, Tingting Ren, Qinqin Liu, Xingyu Chang, Meng Xie, Keqin Hua, Junjun Qiu","doi":"10.1093/pcmedi/pbag003","DOIUrl":"10.1093/pcmedi/pbag003","url":null,"abstract":"<p><strong>Objectives: </strong>Gastric-type adenocarcinoma (GAS), an aggressive subtype of non-human papillomavirus (HPV)-associated (NHPVA) cervical adenocarcinomas (ADC), remains a treatment-refractory disease with poor prognosis. This study aims to explore the oncogenic mechanism and efficacious therapeutic target of GAS.</p><p><strong>Methods: </strong>We included 19 NHPVA and 153 HPVA ADC patients from our center to investigate clinicopathological features. We collected 3 GAS and 2 usual-type endocervical adenocarcinomas (UEA) for single-cell RNA sequencing and T-cell receptor sequencing. We conducted immunohistochemical staining of 25 GAS and 25 UEA samples and multicolor immunohistochemical staining of 2 GAS samples for validation. We explored the efficacy of anti-clusterin (OGX-011) and/or cisplatin (DDP) for GAS based on GAS-derived tumoroids.</p><p><strong>Results: </strong>Based on clinical data, we clinicopathologically verified the malignancy of GAS. Through single-cell RNA sequencing, we delineated key cell subtypes including GAS epithelial cells, \"GAS-enriched fibroblasts\", \"GAS-associated γδT cells\", and CD8+ exhausted T cells enduring heat stress and contributing to GAS aggressive phenotype. Regarding validation, we verified clusterin (CLU)-associated heat stress, highlighted the potential role of CLU-associated stress in promoting immune escape, and established a four-gene signature (CLU, PDGFB, TIGIT, and C3) indicating poor prognosis of GAS induced by CLU-associated stress and immune escape. Based on GAS-derived tumoroids retaining the histological features, CLU-associated stress, and genetic profile of parental tumor, we validated the anti-tumor and sensitizing DDP efficacy of targeting CLU.</p><p><strong>Conclusion: </strong>CLU-associated heat stress of key cell subtypes contributed to the malignant GAS microenvironment. Additionally, we pioneeringly constructed GAS-derived tumoroids and suggested that combining CLU-targeted treatment and DDP could improve the therapeutic efficacy for GAS.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"9 1","pages":"pbag003"},"PeriodicalIF":6.4,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13006877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147515179","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":"Regulation of cancer cell adhesion, progression, and epithelial-to-mesenchymal transition by N-glycosylation.","authors":"Jianguo Gu","doi":"10.1093/pcmedi/pbag002","DOIUrl":"10.1093/pcmedi/pbag002","url":null,"abstract":"","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"9 1","pages":"pbag002"},"PeriodicalIF":6.4,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12883984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146158769","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":"Spatial proteomics in precision medicine: technologies, bioinformatics, and translational applications.","authors":"Yiwen Li, Yusheng Zhang, Ying Zhang, Qing Wang, Boyang Ji, Hongjun Yang, Xianyu Li","doi":"10.1093/pcmedi/pbaf040","DOIUrl":"10.1093/pcmedi/pbaf040","url":null,"abstract":"<p><p>Protein function is inherently spatial: the same molecule can elicit distinct biological outcomes depending on its localization, interacting partners, and surrounding microenvironment. Spatial proteomics enables systematic <i>in situ</i> characterization of protein localization, abundance, and interactions across subcellular to tissue scales, surpassing the resolution and contextual information accessible to conventional bulk proteomics. Recent technological advances including DNA-barcoded multiplexing methods, cyclic fluorescence platforms, and mass spectrometry imaging have substantially increased multiplexing capacity, sensitivity, and spatial accuracy. These capabilities directly support clinically relevant applications, such as tumor immune microenvironment analysis, mapping of protein aggregation in neurodegeneration, growth factor dynamics during tissue repair, patient stratification, pharmacodynamic mapping, and target-engagement assessment. Computational innovations, including graph neural networks, self-supervised embeddings, and workflow management tools (e.g. Snakemake, Nextflow), further enhance cell segmentation, noise reduction, and multi-modal data integration, enabling extraction of robust, spatially resolved proteomic information from complex tissues. Future research will aim to standardize protocols, enable real-time clinical analysis, and develop 3D spatial proteome maps to advance spatial proteomics toward precision diagnostics and targeted therapies.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"9 1","pages":"pbaf040"},"PeriodicalIF":6.4,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12868980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146126634","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":"Antibiotic exposure impairs the efficacy of first-line chemoimmunotherapy in non-small cell lung cancer through the regulation of gut microbiome and bile acid metabolism.","authors":"Hanyan Xu, Jia Yu, Lijing Xia, Xiong Lei, Liwen Zhou, Pengcheng Lin, Shanshan Su, Yuping Li, Chengshui Chen","doi":"10.1093/pcmedi/pbag001","DOIUrl":"10.1093/pcmedi/pbag001","url":null,"abstract":"<p><strong>Objective: </strong>Previous antibiotic therapy is acknowledged to potentially reduce the efficacy of single-agent immune checkpoint inhibitors. Nevertheless, the impact of antibiotics on the results for patients undergoing chemoimmunotherapy remains unclear. This research investigated the influence of antibiotic treatment on the effectiveness of chemoimmunotherapy in advanced non-small cell lung cancer (NSCLC).</p><p><strong>Methods: </strong>We recorded the characteristics of patients with advanced NSCLC and assessed potential associations between the use of antibiotics and the efficacy of chemoimmunotherapy. A mouse model using Lewis lung carcinoma (LLC) cell lines was developed to assess the effects of antibiotics on the gut microbiome and metabolites. Fecal samples were analyzed using 16S rRNA gene sequencing and ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) methods. Mouse fecal and serum samples and 16 human stool samples were used to validate the identified differentially metabolites. Deoxycholic acid (DCA) was further applied to a LLC mouse model.</p><p><strong>Results: </strong>This study included 387 NSCLC patients, among whom 86 patients had used antibiotics within the 30 days before the first cycle of chemoimmunotherapy (ATB group), and 301 patients had not used antibiotics (non-ATB group). Notable discrepancies were observed in overall survival and progression-free survival between the two groups, with overall survival recorded at 18.4 months versus 32.0 months, and progression-free survival at 7.6 months versus 13.0 months, in the ATB and non-ATB groups respectively. At the phylum level, the relative abundances of <i>Proteobacteria, Cyanobacteria</i>, and <i>Deinococcus</i> were increased in the ATB mice, while <i>Firmicutes, Bacteroidetes</i>, and <i>Verrucomicrobia</i> were decreased. We detected significant differences in DCA levels in the fecal and serum samples from mice as well as in the fecal sample from humans between the ATB and non-ATB groups. The respective proportions of CD4+ and CD8+ cells were greater in the non-ATB group than in the ATB group, whereas the proportion of Ki67-positive cells was greater in the ATB group. DCA was applied to LLC mice, and DCA along with chemoimmunotherapy effectively inhibited tumor growth in a LLC mouse model. The expression of programmed cell death ligand 1 increased in the DCA group.</p><p><strong>Conclusions: </strong>Antibiotic exposure is associated with decreased efficacy of chemoimmunotherapy in patients with NSCLC via dysregulation of the gut microbiome and DCA metabolism.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"9 1","pages":"pbag001"},"PeriodicalIF":6.4,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12868978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146126571","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":"IRF7 orchestrates maladaptive smooth muscle cell phenotype switching in atherosclerosis.","authors":"Rundong Cai, Xin Chen, Hongxia Zhang, Qi Wang, Wanrong Xie, Xinghua Pan, Chun Liang, Haiying Zhu","doi":"10.1093/pcmedi/pbaf039","DOIUrl":"10.1093/pcmedi/pbaf039","url":null,"abstract":"<p><strong>Background: </strong>Smooth muscle cells (SMCs) exhibit remarkable plasticity, undergoing extensive phenotypic switching to generate a highly heterogeneous population within atherosclerotic plaques. While recent studies have highlighted the contribution of SMC-derived macrophage-like cells to plaque inflammation, the specific molecular drivers governing the transition to these pathogenic states remain poorly understood.</p><p><strong>Methods: </strong>Here, we re-analyzed single-cell RNA sequencing data from lineage-traced mice to dissect SMC heterogeneity during atherogenesis. Trajectory analysis revealed that SMCs transdifferentiate into a distinct pro-inflammatory macrophage-like subpopulation (macrophage 4) via an intermediate \"stem-endothelial-monocyte\" cell state. Integrated gene regulatory network inference and <i>in silico</i> perturbation modeling identified interferon regulatory factor 7 (IRF7) as a master transcriptional regulator orchestrating this specific pathogenic transition.</p><p><strong>Results: </strong>Clinically, IRF7 expression was significantly upregulated in unstable and advanced human atherosclerotic plaques, correlating strongly with inflammatory macrophage burden. <i>In vivo, ApoE</i> ^-/- mice challenged with a high-fat diet exhibited robust upregulation of IRF7 in aortic plaques, which co-localized with macrophage markers. Crucially, SMC-specific knockdown of <i>Irf7</i> using an AAV-SM22α-shIRF7 vector significantly attenuated atherosclerotic plaque progression, reduced necrotic core formation, and enhanced fibrous cap stability. Mechanistically, <i>Irf7</i> silencing preserved the contractile SMC phenotype and inhibited the accumulation of pro-inflammatory SMC-derived macrophage-like cells within the lesion.</p><p><strong>Conclusions: </strong>These findings identify IRF7 as a critical checkpoint in maladaptive SMC phenotype switching. We demonstrate that IRF7 drives the transdifferentiation of SMCs into a pro-inflammatory macrophage-like state, thereby fueling plaque instability. Consequently, therapeutic strategies capable of inhibiting IRF7-mediated SMC plasticity may prove effective in stabilizing vulnerable atherosclerotic plaques.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"9 1","pages":"pbaf039"},"PeriodicalIF":6.4,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12859258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146107477","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":"Drug pair-derived synergistic therapy of flavonoids luteolin and astragaloside IV promotes neural repair following spinal cord injury via antioxidant and neuroprotective effects.","authors":"Wei Lin, Peng Zhang, Defeng Liu, Yihui Feng, Dongdong Su, Xin Sun, Na Yuan, Xin Zhou, Zhen Liu, Shen Liu, Huiqian Gao, Liming Li, Wenzhao Wang, Ting Tian, Jihui Zheng","doi":"10.1093/pcmedi/pbaf037","DOIUrl":"10.1093/pcmedi/pbaf037","url":null,"abstract":"<p><strong>Background: </strong>Spinal cord injury (SCI) induces a damaging oxidative microenvironment exacerbating secondary injury. The traditional Chinese medicine (TCM) drug-pair Dangshen and Huangqi, known for antioxidant and neuroprotective effects, yields key components luteolin (Lut) and astragaloside IV (AST), both promising in oxidative stress-related neurological disorders but unexplored in combination for SCI.</p><p><strong>Methods: </strong>We investigated the synergistic antioxidant effects of Lut-AST combination therapy using an <i>in vitro</i> oxidative stress model in PC12 cells, and subsequently assessed its neuroprotective efficacy through behavioral assessments and histopathological analyses in a rat model of severe SCI. Finally, we utilized network pharmacology and molecular docking to predict and explore the potential of the Lut-AST drug pair for treating SCI through multi-target therapy.</p><p><strong>Results: </strong>Our study demonstrated that the Lut-AST drug pair synergistically attenuated oxidative stress-induced cytotoxicity. Lut-AST treatment effectively promoted nerve repair and functional recovery in SCI rats. A significant recovery of motor functions was observed accompanied byh reduced accumulation of reactive oxygen species. Neuroinflammation and glial scars were largely alleviated, while the distribution of 5-hydroxytryptamine and neurofilament-positive nerve fibers was evidently increased.</p><p><strong>Conclusion: </strong>These findings confirm Lut-AST's therapeutic efficacy in mitigating post-SCI oxidative stress and unveil novel insights into traditional Chinese medicine's inherent multi-component synergistic interactions, suggesting potentiated outcomes through integrated antioxidant mechanisms and multi-target regulation. This study provides a paradigm for optimizing TCM-derived neuroprotective strategies by leveraging component synergy, informing novel combinatorial therapies for SCI management.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"9 1","pages":"pbaf037"},"PeriodicalIF":6.4,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12856357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146107493","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":"Obesity care in Chinese adults: from evidence to clinical practice.","authors":"Jing An, Qingyi Jia, Yan Huang, Yuzi Cao, Yaqian Duan, Huijie Zhang, Sheyu Li","doi":"10.1093/pcmedi/pbaf036","DOIUrl":"10.1093/pcmedi/pbaf036","url":null,"abstract":"<p><p>More than 500 million Chinese adults suffered from overweight or obesity in 2023. The pandemic of obesity consumes healthcare and economic resources by imposing enormous burden from its complications such as cardiovascular, kidney and metabolic diseases. In response, China launched a series of important policy changes including \"Weight Management Year\", facilitating the engagement of public health, clinical practitioners, industry and stakeholders in different fields. The shift triggered rapid evolution of technologies in obesity care including both treatment and prevention, which added great opportunities for all stakeholders. Nevertheless, challenges exist, including misdiagnosis of obesity secondary to other diseases, population disparity, indirect evidence supported by trials conducted in other ethnic groups, health inequalities and the collaboration across stakeholders with diverse backgrounds. Traditional Chinese diets such as Jiangnan Diet and activities such as Tai Chi represent tradition-based lifestyle interventions that provide Chinese people with cultural benefits. The evolution of technologies, especially digital healthcare and novel medications, will play critical roles in future obesity care in China. Policy makers and clinical and public health practitioners must make every effort to address the urgent crisis posed by obesity pandemic in China.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"8 4","pages":"pbaf036"},"PeriodicalIF":5.0,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12723657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145828546","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":"RNA modifications in health and disease: from mechanistic insights to therapeutic applications.","authors":"Yiting Chen, Dulin Ding, Xing Tang, Rui Ma, Jian-Kang Zhou","doi":"10.1093/pcmedi/pbaf035","DOIUrl":"10.1093/pcmedi/pbaf035","url":null,"abstract":"<p><p>RNA modifications encompass a series of dynamic chemical changes and editing events on RNA molecules, playing a pivotal role in essential physiological processes such as embryonic development, immune response, and the maintenance of cell homeostasis. By influencing RNA stability, splicing, translation, and intermolecular interactions, RNA modifications serve as crucial mechanisms regulating gene expression at the post-transcriptional level. Dysregulation of the modification machineries or aberrant modification patterns is closely associated with the onset and progression of various diseases, including tumors, metabolic disorders, cardiovascular diseases, and neurological and immune conditions, making them potential biomarkers for disease diagnosis, prognosis, and treatment. In this review, we summarize the molecular mechanisms of major RNA modifications, emphasize their functions in health and disease, and discuss their diagnostic and therapeutic value in pathological contexts.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"8 4","pages":"pbaf035"},"PeriodicalIF":5.0,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12723240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145828564","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":"Endocrinologists in golden age: opportunities enabled by artificial intelligence.","authors":"Bing Li, Qingzheng Wu, Zhaohui Lyu","doi":"10.1093/pcmedi/pbaf030","DOIUrl":"10.1093/pcmedi/pbaf030","url":null,"abstract":"","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"8 4","pages":"pbaf030"},"PeriodicalIF":5.0,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12690197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145744896","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":"Insights into the mechanisms of microRNAs in hepatoblastoma: from diagnosis to treatment.","authors":"Meng Kong, Shisong Zhang, Xiang Ma","doi":"10.1093/pcmedi/pbaf034","DOIUrl":"10.1093/pcmedi/pbaf034","url":null,"abstract":"<p><p>Hepatoblastoma (HB) is the most common malignant liver tumor in children. Early diagnosis and effective treatment are crucial for improving the prognosis of children with HB. In recent years, microRNAs (miRNAs), an important class of noncoding RNA molecules, have been increasingly recognized for their key regulatory roles in the occurrence, development, and treatment of HB. This review systematically reviews the expression characteristics, molecular mechanisms, and potential application value of miRNAs in the diagnosis and treatment of HB. Research indicates that the interaction network between miRNAs and long noncoding RNAs and circular RNAs has a significant effect on the development of HBs. miRNAs regulate signaling pathways, such as the Wnt/β-catenin, mitogen-activated protein kinase, phosphatidylinositol 3-kinase/protein kinase B, and Janus kinase 2/signal transducer and activator of transcription 3 pathways, and also play critical roles in the biological behavior of HBs. Furthermore, the progress of preclinical research on miRNAs as biomarkers and therapeutic targets provides new ideas and directions for precision medicine in HB. Finally, this article looks forward to the future development directions of miRNAs in precision medicine for HBs, emphasizing their important potential in improving diagnostic accuracy and treatment efficacy.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"8 4","pages":"pbaf034"},"PeriodicalIF":5.0,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12699220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145757817","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}