Precision Clinical Medicine最新文献

{"title":"Artificial intelligence-driven peptide blocks gasdermin pyroptosis and alleviates inflammation.","authors":"Mingsheng Liu, Hongqing Zhou, Min Wu","doi":"10.1093/pcmedi/pbag004","DOIUrl":"https://doi.org/10.1093/pcmedi/pbag004","url":null,"abstract":"","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"9 1","pages":"pbag004"},"PeriodicalIF":5.0,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12983214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147469574","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":"Linking first-pass reperfusion success to proteomic markers in large and medium vessel ischemic stroke: an exploratory study.","authors":"Crhistian-Mario Oblitas, Sabela Fernández-Rodicio, Manuel Rodríguez-Yáñez, Emilio Rodríguez-Castro, Arturo Gonzalez-Quintela, Jacobo Porto-Álvarez, Javier Martínez-Fernández, Miguel Blanco, Jose Luis Taboada, Sara Martnez-Reiriz, Susana B Bravo, Carmen Pena, José Castillo, Maria Luz Alonso-Alonso, Pablo Hervella, Antonio J Mosqueira, Ramón Iglesias-Rey","doi":"10.1093/pcmedi/pbag008","DOIUrl":"10.1093/pcmedi/pbag008","url":null,"abstract":"","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"9 1","pages":"pbag008"},"PeriodicalIF":5.0,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13006874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147515243","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":"Beyond CAR-T and oncology: broadening chimeric antigen receptor technologies across cell types and diseases.","authors":"Xiaohong Liu, Hongye Gao, Jianhua Yu","doi":"10.1093/pcmedi/pbag007","DOIUrl":"10.1093/pcmedi/pbag007","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR)-engineered immune cells have revolutionized cancer immunotherapy, expanding from the established success of CAR-T cells to a diverse array of cellular platforms. While seven Food and Drug Administration-approved CAR-T cell products demonstrate unprecedented efficacy in hematologic malignancies, significant limitations persist, including severe inflammatory toxicities, resistance in solid tumors, and manufacturing barriers. These challenges have catalyzed extensive research to extend CAR engineering into alternative effector cell types, such as unconventional T cell subsets, natural killer (NK) cells, macrophages, neutrophils, and dendritic cells, as well as non-immune platforms. Each cell type exhibits distinct antitumor mechanisms, persistence profiles, safety characteristics, and manufacturing requirements, positioning them to address complementary therapeutic needs. This review provides a comprehensive overview of diverse CAR-engineered cellular platforms, encompassing their biological properties, advantages, sourcing strategies, and manufacturing processes, alongside current clinical progress and optimization approaches. Beyond oncology, these platforms have demonstrated significant potential in treating autoimmune diseases, infections, cardiac fibrosis, and senescence-associated disorders. By leveraging distinct immune and non-immune cell types to mediate cytotoxicity or suppress pathogenic cells, CAR technology provides versatile therapeutic avenues across varied disease contexts. Through synthesis of recent advances in CAR platform diversity, this review identifies opportunities for targeted optimization and explores future directions for broadening CAR-based therapeutic applications.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"9 1","pages":"pbag007"},"PeriodicalIF":5.0,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12983217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147469568","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":"Pressure cycling technology-assisted data-independent acquisition proteomics reveals molecular alterations and potential therapeutic targets in minor glomerular abnormalities.","authors":"Ling Li, Yingying Ling, Fei Cai, Yi Zhong, Hao Yang, Fang Liu, Guisen Li, Xinfang Xie, Rajeev K Singla, Dengyan Ma, Yong Zhang","doi":"10.1093/pcmedi/pbag006","DOIUrl":"10.1093/pcmedi/pbag006","url":null,"abstract":"<p><strong>Background: </strong>Minor glomerular abnormalities (MGAs) are histopathologically heterogeneous renal lesions with subtle structural changes and latent clinical manifestations, yet their molecular mechanisms remain poorly characterized and underexplored.</p><p><strong>Methods: </strong>In this study, we employed pressure cycling technology-assisted sample preparation combined with data-independent acquisition mass spectrometry to systematically compare the proteomic profiles of distant non-neoplastic tissues (<i>n</i> = 24) and MGA tissues (<i>n</i> = 27).</p><p><strong>Results: </strong>A total of 9 529 protein groups were quantified with a false discovery rate < 1%, and 1 338 differentially expressed protein groups were identified (fold-change > 2 or < 0.5, <i>P</i> < 0.05), including 190 downregulated and 1 148 upregulated protein groups in MGA tissues. Gene ontology analysis revealed that the downregulated proteins were enriched in cell adhesion, ion binding, and molecular transport, whereas the upregulated proteins were enriched in transcriptional regulation, DNA replication/repair, and nucleic acid binding. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated inhibition of metabolic pathways and the peroxisome proliferator-activated receptor signaling pathway, as well as the activation of basal transcription factors and nucleotide excision repair in MGAs. Further screening revealed 13 core upregulated nuclear proteins (e.g. YY1, TAF9, RFC1, and POLR1D) with a >90% detection rate in MGA tissues; these proteins are functionally associated with renal inflammation, cell proliferation, and the DNA damage response.</p><p><strong>Conclusion: </strong>Our study establishes a high-resolution proteomic landscape of MGAs, provides novel insights into their molecular pathogenesis, and identifies potential tissue biomarkers and therapeutic targets. The pressure cycling technology-assisted data-independent acquisition workflow also offers a robust technical framework for proteomic analysis of microscale renal biopsy samples.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"9 1","pages":"pbag006"},"PeriodicalIF":5.0,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12999293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499957","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 genomics and brain spatial transcriptomic atlas for precision medicine.","authors":"Wei Xiong, Alexander Hindeleh, Charles Wang","doi":"10.1093/pcmedi/pbag005","DOIUrl":"10.1093/pcmedi/pbag005","url":null,"abstract":"","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"9 1","pages":"pbag005"},"PeriodicalIF":5.0,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12983213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147469579","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":"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":5.0,"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":5.0,"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":5.0,"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":5.0,"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":5.0,"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}