Precision Clinical Medicine最新文献

{"title":"The emerging potential of the psycho-cardiovascular interaction network in precision medicine.","authors":"Jiayu Liao","doi":"10.1093/pcmedi/pbag026","DOIUrl":"https://doi.org/10.1093/pcmedi/pbag026","url":null,"abstract":"","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"9 3","pages":"pbag026"},"PeriodicalIF":6.4,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13598483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040962","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":"Psycho-cardiovascular interaction network in cardiovascular health and disease: signaling pathways and molecular mechanisms.","authors":"Zexi Li, Fanghui Li, Chunyi Yan, Lianrui Xiang, Aobo Gong, Ying Cao, Yifan Zhou, Wei Zhang, Rui Zeng","doi":"10.1093/pcmedi/pbag025","DOIUrl":"10.1093/pcmedi/pbag025","url":null,"abstract":"<p><p>Extensive evidence indicates a strong association between psychological and psychiatric factors and cardiovascular disease (CVD). Psychological and psychiatric factors, including depression, anxiety, and chronic stress, are associated with an increased risk of CVD and adverse cardiovascular outcomes. Furthermore, this association is bidirectional, as patients with CVD have a notably higher risk of developing comorbid mental disorders. We propose the psycho-cardiovascular interaction network (PCIN) to elucidate the multilevel integrated regulatory mechanisms linking psychological status and cardiovascular function. In this review, we synthesize epidemiologic evidence, summarize the major mechanisms through which these factors may influence cardiovascular function, and focus on key signaling pathways within the PCIN, including BDNF, PROK/PKR, MAPK, 5-HT/5-HT₂A-R, and NLRP3 inflammasome pathways, which may mediate bidirectional brain-heart communication and mental disorder-CVD comorbidity. On the basis of the PCIN framework, we discuss integrated intervention strategies, including nonpharmacological approaches and molecularly targeted therapies for brain-heart axis-informed management. Future research should focus on the translational potential of psycho-cardiovascular regulatory molecules as therapeutic targets and candidate biomarkers, and high-quality studies are urgently needed to elucidate the long-term effects of psychological interventions on cardiovascular health outcomes and their molecular mechanisms. In addition, integrating psychosocial phenotypes with molecular biomarkers may facilitate individualized risk assessment and inform brain-heart axis-based prevention and therapeutic strategies.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"9 3","pages":"pbag025"},"PeriodicalIF":6.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13575935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148978175","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":"Histone modifications: mechanisms, metabolic regulation, and therapeutic targeting in cancer.","authors":"Lingli Wang, Shiying Li, Xiaoyan Hu, Kui Ming Chan, Yang Meng, Junhong Han","doi":"10.1093/pcmedi/pbag024","DOIUrl":"10.1093/pcmedi/pbag024","url":null,"abstract":"<p><p>Histone post-translational modifications are central regulators of chromatin organization and genome function, acting independently of alterations in DNA sequence. This review comprehensively summarizes the multifaceted roles of major histone modifications, including acetylation, methylation, ubiquitination, phosphorylation, and emerging metabolism-linked acylations, in governing critical DNA-templated processes such as replication, transcription, and the DNA damage response. We further discuss the concept of the nuclear metabolic microenvironment, in which local metabolite availability and enzyme activity directly influence the deposition of histone acylation marks and thereby connect metabolic state to chromatin regulation. We also examine how dysregulation of these pathways promotes tumor initiation and progression, facilitates immune evasion, and drives therapeutic resistance. On this basis, we evaluate current therapeutic strategies targeting histone-modifying machinery in cancer, including approved epigenetic drugs, agents in clinical development, biomarker-guided applications, resistance mechanisms, and combination approaches. We further distinguish direct pharmacological targeting of histone writers, erasers, and readers separately from indirect interventions against upstream kinases, metabolic pathways, or organelle-level metabolic remodeling. Together, these observations highlight the biological and translational importance of histone modifications in cancer and support continued development of mechanism-informed and biomarker-guided epigenetic therapies in precision oncology.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"9 3","pages":"pbag024"},"PeriodicalIF":6.4,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13587097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149008979","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":"Artificial intelligence-based multimodal integration of ultrasound and digital breast tomosynthesis for breast-level risk classification.","authors":"Yujie Tan, Zhenjun Huang, Junwei Li, Ying Zhong, Qinyue Yao, Rui Chen, Yunfang Yu, Yaping Yang, Herui Yao","doi":"10.1093/pcmedi/pbag023","DOIUrl":"10.1093/pcmedi/pbag023","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer imaging frequently combines ultrasound (US), digital mammography (DM), and digital breast tomosynthesis (DBT), yet integrating complementary findings remains labor-intensive.</p><p><strong>Methods: </strong>We developed a parallel-branch deep learning framework for breast-level risk classification from paired US, DM, and DBT examinations. The models were trained on 2187 breasts and evaluated in an internal validation cohort of 632 breasts and an independent pathology-confirmed cohort of 500 breasts. Six single- and dual-modality models were compared.</p><p><strong>Results: </strong>In the internal validation cohort, US-DBT achieved the highest observed area under the curve (AUC) of 0.944 (95% CI, 0.926-0.963), exceeding US-DM and DM-DBT but not US; its sensitivity was 0.860 (95% CI, 0.805-0.904) and specificity was 0.904 (95% CI, 0.871-0.930). In the pathology-confirmed cohort, US-DBT achieved an AUC of 0.934 (95% CI, 0.913-0.955), exceeding US and DM-DBT but not US-DM. Its specificity was higher than that of all three models (0.955; 95% CI, 0.927-0.975; all adjusted <i>P </i>< 0.001), with a positive predictive value (PPV) of 0.958 (95% CI, 0.931-0.977) and sensitivity of 0.850 (95% CI, 0.807-0.887), which did not differ significantly from any of the three models. Performance remained favorable in dense breasts, lesions <2 cm, and lower-suspicion Breast Imaging Reporting and Data System (BI-RADS) strata.</p><p><strong>Conclusions: </strong>These findings identify improved specificity as the principal added value of US-DBT and support its potential use as an adjunctive breast-level tool for refining positive imaging findings and prioritizing further diagnostic evaluation. Prospective validation in representative screening populations is required.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"9 3","pages":"pbag023"},"PeriodicalIF":6.4,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148956622","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":"Perioperative gut microbial ecology: a new frontier for improving the prognosis of hepatocellular carcinoma surgery.","authors":"Dong Hu, Zhiwei Wang, Yifei Xue, Xiaoming Li, Yuanyuan Li, Shaopeng Liu, Linbo Gao, Haichao Liu, Hongxian Yan","doi":"10.1093/pcmedi/pbag021","DOIUrl":"10.1093/pcmedi/pbag021","url":null,"abstract":"<p><p>For patients diagnosed with hepatocellular carcinoma (HCC), surgical intervention remains the primary treatment modality. Nonetheless, challenges such as poor postoperative prognosis and the potential for recurrence contribute significantly to patient suffering. During the perioperative period, the stability of the gut microbiota in patients with HCC is significantly disrupted. This disruption can substantially affect the liver microenvironment and ultimately influence postoperative outcomes. Notably, the metabolic reprogramming of the liver induced by gut microbiota dysbiosis, persistent inflammation, and suppressed immune surveillance are key factors in HCC recurrence. Consequently, the gut microbiota has emerged as a critical risk factor in improving perioperative outcomes for patients with HCC. In this review, we summarize the factors contributing to changes in the gut microbiota during the perioperative period in patients with HCC, as well as the potential mechanisms by which gut microbiota dysbiosis affects prognosis. More importantly, we have proposed strategies based on the aforementioned mechanisms affecting prognosis, including restoring the gut microbiota, repairing the gut-liver barrier, providing perioperative relief, and enhancing liver regeneration. Further, this review also outlines potential challenges in clinical applications aimed at improving postoperative outcomes for HCC patients through gut microbiota-based interventions, particularly regarding sampling and patient susceptibility stratification. Collectively, these studies will further advance the development of personalized therapies targeting the microbiome, ultimately improving prognostic strategies for patients undergoing surgical intervention for HCC.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"9 3","pages":"pbag021"},"PeriodicalIF":6.4,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13484014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798538","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 the genetic code: orchestrating epigenetic and immune landscapes with multivalent mRNA-exosome vaccines.","authors":"Huiqin Bian, William Tse, Gang Huang, Shujun Liu","doi":"10.1093/pcmedi/pbag019","DOIUrl":"10.1093/pcmedi/pbag019","url":null,"abstract":"<p><p>mRNA therapeutics are transitioning from transient anti-viral vaccines into precise cancer immunotherapies capable of orchestrating potent antigen-specific T-cell and humoral responses. However, therapeutic resistance within immunologically \"cold\" tumors remains a formidable barrier, necessitating multiaxial optimization across transcript architecture, neoantigen selection, delivery vector engineering, and tumor microenvironment (TME) reprogramming. This review synthesizes critical breakthroughs in mRNA biochemistry-including chemical nucleotide modifications, optimized untranslated regions, structural codon adjustments, and stringent purification methodologies-that extend transcript longevity while limiting off-target reactogenicity to maximize functional antigen expression. We evaluate multiomic neoantigen discovery workflows leveraging genomics, transcriptomics, immunoproteomics, and computational HLA-binding algorithms to refine patient-specific target selection. Next, we dissect advanced lipid nanoparticles, surface-functionalized biomaterials, and engineered extracellular vesicles optimized to enhance antigen-presenting cell tropism and lymphoid homing. We further detail how vaccine-induced cytokine fluxes actively remodel the TME, successfully reversing local immune tolerance and driving robust effector leukocyte infiltration into the tumor stroma. Specifically, we highlight the convergence of mRNA-mediated cytokine signaling and epigenetic imprinting, which cooperatively induce trained immunity for durable preventive surveillance. Finally, we delineate rational combinations with immune checkpoint blockades while addressing translational challenges: identifying predictive biomarkers, mapping presentation kinetics, and structuring adaptive clinical trial frameworks.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"9 3","pages":"pbag019"},"PeriodicalIF":6.4,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13445983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148686265","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":"Multi-omics profiling of recurrence-associated extrachromosomal circular DNA characteristics and its prognostic potential in lung adenocarcinoma.","authors":"Xinyu Zhao, Xingyi Du, Shenqiao Yang, Su Chen, Chunlan Pu, Hengrui Fan, Mingbiao Qiao, Yi Yang, Yuanbiao Guo, Zhiyun Guo","doi":"10.1093/pcmedi/pbag017","DOIUrl":"10.1093/pcmedi/pbag017","url":null,"abstract":"<p><strong>Objective: </strong>Extrachromosomal circular DNA (eccDNA) contributes to tumorigenesis, but its role in tumor recurrence remains unclear. This study aimed to systematically characterize eccDNA profiles in recurrent and non-recurrent early-stage lung adenocarcinoma (LUAD) patients and evaluate their potential as prognostic biomarkers.</p><p><strong>Methods: </strong>Tumor tissues, matched adjacent non-tumor tissues, and plasma were collected from patients with early-stage LUAD. All patients underwent a 2-year postoperative follow-up to identify recurrence. Circle-seq and multi-omics analyses were applied to profile eccDNA landscapes in recurrent and non-recurrent patients.</p><p><strong>Results: </strong>eccDNAs in recurrent LUAD patients exhibited significantly distinct features, including higher GC content, enhanced structural stability, increased expression levels, and enrichment in transcriptionally active regions. Recurrence-associated eccDNAs carry oncogenes and regulate pathways involved in tumor migration, invasion, and immune evasion via suppression of immune factor receptors. A recurrence risk model based on seven plasma eccDNA marker genes effectively stratified patients, with high-risk patients exhibiting significantly poorer disease-free survival.</p><p><strong>Conclusion: </strong>These findings highlight the characteristics of eccDNAs in LUAD recurrence and their potential as prognostic biomarkers, providing preliminary multi-omics evidence for understanding the role of eccDNA in LUAD recurrence and laying the groundwork for future mechanistic studies and clinical translation.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"9 3","pages":"pbag017"},"PeriodicalIF":6.4,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13421084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148631809","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":"GALNT7 promotes the malignant progression of gastrointestinal stromal tumors by regulating KIT O-GalNAc glycosylation.","authors":"Jiahao Liu, Sihan Wu, Yunfei Wang, Ge Zhang, Jiehan Li, Zhen Wang, Yuhan Yin, Hao Liu, Sanfei Peng, Yang Fu","doi":"10.1093/pcmedi/pbag016","DOIUrl":"10.1093/pcmedi/pbag016","url":null,"abstract":"<p><strong>Background: </strong>Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract and is mainly driven by activating <i>KIT</i> or <i>PDGFRA</i> mutations. Although tyrosine kinase inhibitors (TKIs) improve outcomes, primary and acquired resistance remain major challenges, especially in high-risk and wild-type GIST. Protein O-linked N-acetylgalactosamine (O-GalNAc) glycosylation regulates protein stability and signaling, but its role in GIST remains unclear.</p><p><strong>Methods: </strong>Bulk RNA-seq, proteomic, and single-cell RNA-seq data were integrated to identify O-glycosylation-related programs and key glycosyltransferases in GIST. Functional assays in GIST-T1 and GIST-882 cells, together with xenograft models, were performed to assess the effects of GalNAc-transferase 7 (GALNT7). GALNT7-KIT interaction, KIT O-GalNAcylation, and protein stability were examined by co-immunoprecipitation, VVA lectin blotting, confocal microscopy, and cycloheximide chase assays. Benzyl-α-GalNAc was evaluated as an O-glycosylation-targeting strategy <i>in vitro</i> and <i>in vivo</i>.</p><p><strong>Results: </strong>O-glycosylation signatures were enriched in high-risk GIST and correlated with pathological risk. High O-glycosylation scores co-segregated with elevated copy-number variation in a fibroblast-like malignant cell population. <i>GALNT7</i> was identified as a hub gene, upregulated in GIST, and associated with poor progression-free survival. GALNT7 promoted GIST cell growth, migration, and xenograft formation. Mechanistically, GALNT7 interacted with KIT, catalyzed its Tn-antigen O-GalNAcylation, increased KIT protein stability, and sustained PI3K/AKT and MAPK/ERK1/2 signaling. Benzyl-α-GalNAc reduced KIT O-GalNAcylation and stability, attenuated GALNT7-driven phenotypes, and inhibited xenograft growth.</p><p><strong>Conclusions: </strong>GALNT7-mediated O-GalNAc glycosylation stabilizes KIT and drives GIST progression. GALNT7 may serve as a prognostic biomarker and therapeutic target in GIST.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"9 2","pages":"pbag016"},"PeriodicalIF":6.4,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13256011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148253821","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":"Trispecific antibodies: is more always better? Advances and boundaries.","authors":"Xun Liao, Wenjie Hou, Junxiu Zhou, Liang Feng, Rui Ma, Yong Peng","doi":"10.1093/pcmedi/pbag015","DOIUrl":"10.1093/pcmedi/pbag015","url":null,"abstract":"","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"9 2","pages":"pbag015"},"PeriodicalIF":6.4,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13221634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148139061","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":"Calming sterile inflammation in intervertebral disc degeneration: taurine disrupts mitochondria-cGAS-STING signaling via autophagy enhancement.","authors":"Shuangjia Zai, Huofeng Wu, Xuan You, Chen Liu, Zhaoyu Li, Benkui Hua, Chengyu Hou, Zhengguang Li, Liang Zhang","doi":"10.1093/pcmedi/pbag013","DOIUrl":"10.1093/pcmedi/pbag013","url":null,"abstract":"<p><strong>Background: </strong>Intervertebral disc degeneration (IVDD) is a major pathological process leading to low back pain, closely associated with the functional decline of nucleus pulposus progenitor cell (NPPC). The role of the cGAS-STING pathway in mediating DNA-sensing-associated inflammation and senescence in IVDD has not been fully elucidated.</p><p><strong>Methods: </strong>This study integrated genetics, computational biology, cellular experiments, and animal models to systematically investigate whether taurine (TAU) exerts protective effects by modulating this pathway.</p><p><strong>Results: </strong>Mendelian randomization analysis suggested a causal relationship between higher TAU levels and reduced risk of IVDD. Molecular docking and dynamics simulations demonstrated that TAU stably binds to cGAS and STING. In both degenerated human nucleus pulposus (NP) tissues and an H₂O₂-induced NPPC senescence model, the cGAS-STING pathway was significantly activated. TAU intervention maintained mitochondrial function, reduced cytosolic mtDNA leakage, and enhanced autophagic degradation of STING, thereby suppressing downstream TBK1-IRF3/NLRP3 inflammatory signaling and subsequently alleviating cellular senescence, inflammatory responses, and apoptosis. TAU treatment effectively delayed intervertebral disc height loss, histopathological progression, and pain sensitivity in a rat IVDD model.</p><p><strong>Conclusion: </strong>This study is the first to reveal that TAU mitigates IVDD through multi-targeted modulation of the \"mitochondria-cGAS-STING\" axis, providing a theoretical foundation for its translational application as a disease-modifying agent.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"9 2","pages":"pbag013"},"PeriodicalIF":6.4,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13213379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148057199","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}