Clinical and Experimental Medicine最新文献

{"title":"Clonal dynamic changes during the progression of myelodysplastic neoplasms to secondary acute myeloid leukemia: a paired-sample comparison.","authors":"Che-Wei Ou, Hsiao-Wen Kao, Tung-Liang Lin, Ming-Chung Kuo, Jin-Hou Wu, Hung Chang, Lee-Yung Shih","doi":"10.1007/s10238-026-02242-z","DOIUrl":"https://doi.org/10.1007/s10238-026-02242-z","url":null,"abstract":"<p><p>Patients with myelodysplastic neoplasms (MDS) have a risk of secondary acute myeloid leukemia (sAML) transformation, but previous studies on the paired samples at both MDS and sAML were very rare. This study aimed to investigate the genetic changes during the progression from MDS to sAML by comparing both phases of MDS at diagnosis and sAML in the same individuals. Seventy-nine paired matched samples of MDS at diagnosis and sAML phase were examined for 32 gene mutations commonly occurring in myeloid neoplasms, including epigenetic regulators, cohesin complex, spliceosome complex, signaling pathway, tumor suppressors, and transcription factors by next-generation sequencing. The acquisition of gene mutations involving signaling pathway and transcription factors was significantly more frequent during the progression to sAML compared to other groups of genes. Mutations involving epigenetic regulators, cohesin complex, and spliceosome complex were generally stable or expanded when disease progressed. Loss of gene mutations was rare, and all mutations showed no apparent decline in their variant allele frequencies except STAG2 mutation. RUNX1 mutations were characterized by acquisition or clonal expansion with no loss or decline during disease progression. TP53 mutations exhibit unique mutational complexity and evolutionary patterns. The dynamic distribution pattern of various gene mutations remained similar regardless of BM blast counts at MDS or the rate of disease progression. Our results demonstrated a distinct pattern of clonal changes in different groups of gene mutations during the progression from MDS to sAML.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148387378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silibinin promotes hepatocyte proliferation through PINK1/Parkin-mediated mitophagy to alleviate acetaminophen-induced liver injury.","authors":"Fengming Xu, Mohamed Albadry, Olaf Dirsch, Uta Dahmen","doi":"10.1007/s10238-026-02218-z","DOIUrl":"10.1007/s10238-026-02218-z","url":null,"abstract":"<p><p>Acetaminophen (APAP) intoxication is a common cause of liver injury. Silibinin has demonstrated potent hepatoprotective properties. However, its underlying mechanisms in APAP-induced liver injury (AILI) remain unclear. Autophagy is a critical adaptive response in AILI, contributing to the clearance of damaged mitochondria and the attenuation of oxidative stress. Therefore, we focused primarily on investigating the role of autophagy in mediating the hepatoprotective effects of silibinin. The effects of silibinin were evaluated in both AML12 cells and a C57BL/6J mouse model of AILI. Both the in vitro and in vivo experiments comprised four groups: a control group, an AILI model group, a silibinin treatment group, and a silibinin plus autophagy inhibitor group using PINK1-siRNA in cell culture and 3-Methyladenine in the animal experiment. Following induction of the AILI model in mice with APAP at a dose of 300 mg/kg, the animals received the designated interventions for five consecutive days. Histopathological alterations were assessed using hematoxylin-eosin staining. Hepatocyte proliferation and apoptosis were evaluated using the CCK-8 assay and immunohistochemical staining for Ki-67 and cleaved caspase-3, respectively, as well as ELISA for Cyclin D1. Liver function was assessed by serum biochemical analysis of alanine aminotransferase, aspartate aminotransferase, total bilirubin, and albumin. Mitochondrial oxidative stress-related parameters, including superoxide dismutase and malondialdehyde, were measured using colorimetric assays. The expression of autophagy-related genes and proteins (PINK1, Parkin, AMPK, LC3 and p62) was analyzed by quantitative PCR, immunofluorescence, and Western blotting. Transmission electron microscopy was employed to examine mitochondrial ultrastructure and the formation of autolysosomes in mouse liver tissue. In AML12 cells, silibinin mitigated AILI by activating the PINK1/Parkin pathway, thereby promoting mitophagy and enhancing cell proliferation. Co-treatment with autophagy inhibitor PINK1-siRNA attenuated these protective effects of silibinin. In AILI mice, silibinin treatment markedly improved liver function, attenuated inflammatory responses, restored mitochondrial function, and enhanced hepatocyte proliferation. These improvements were associated with increased LC3-II expression and reduced p62 accumulation, indicating enhanced autophagic activity. Notably, the protective benefits of silibinin were significantly attenuated by the autophagy inhibitor 3-Methyladenine. Our findings suggest that silibinin protects against AILI by activating PINK1/Parkin-dependent mitophagy, which mitigates oxidative stress and inflammation while promoting hepatocyte regeneration.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13332896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374930","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 polarization: a receptor-centered framework for macrophage function and therapy in skin diseases.","authors":"Yirou Zhu, Huiyi Yao, Wenzhong Xiang","doi":"10.1007/s10238-026-02194-4","DOIUrl":"10.1007/s10238-026-02194-4","url":null,"abstract":"<p><p>Macrophages are key regulators of cutaneous immunity, but the traditional M1/M2 polarization model cannot fully explain their functional diversity across skin diseases. In this narrative review, we use selected skin diseases to discuss a receptor-centered view of macrophage function and to illustrate a modular \"receptor-pathway-effector\" framework. This perspective places macrophage receptors at the upstream sensing level, where microbial products, tissue damage signals, cytokines, immune complexes, stromal cues, and tumor-derived signals are translated into inflammatory, reparative, fibrotic, or immunosuppressive programs. We summarize representative receptor modules, including pattern-recognition receptors, cytokine and chemokine receptors, Fc and complement receptors, scavenger and efferocytosis receptors, and inhibitory checkpoint receptors. Across psoriasis, atopic dermatitis, autoimmune blistering diseases, lupus, systemic sclerosis, sarcoidosis, leprosy, melanoma, cutaneous T-cell lymphoma, diabetic wounds, and radiation-induced skin injury, these modules help explain macrophage involvement in inflammation, remodeling, host defense, impaired repair, and tumor immune escape. We also discuss selected biomarker and therapeutic examples, while distinguishing clinically explored approaches from preclinical or emerging concepts. This receptor-centered perspective may complement existing views of macrophage heterogeneity and provide a clearer way to link receptor signals with disease-related macrophage functions.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13585795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148359721","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":"Serum GRP78 as a potential biomarker for early liver injury and active fibrogenesis in alcohol-associated liver disease.","authors":"Yongping Liu, Yaojie Shen, Yuxia Yu, Ying Meng, Yan Zheng, Xinyu Jiang, Wei Huang, Kai Yu, Yuan Chen, Xiaoying Wu, Cuirong Chen, Yan Liu","doi":"10.1007/s10238-026-02219-y","DOIUrl":"10.1007/s10238-026-02219-y","url":null,"abstract":"<p><p>Alcohol-associated liver disease(ALD) is an important cause of liver-related lesions and death, mainly caused by long-term or excessive alcohol consumption.Reactive oxygen species (ROS) produced during alcohol metabolism induce an oxidative stress response, which GRP78 playing an important regulatory role. This study aims to investigate the relationship between serum GRP78 levels and liver fibrosis/cirrhosis in ALD patients. A case control study was conducted, involving ALD patients (n = 122) and healthy participants (n = 28). Liver steatosis and fibrosis/cirrhosis was assessed by transient elastography (TE) and biochemical parameters were collected. Serum GRP78 was measured by sandwich ELISA based on two monoclonal anti-GRP78 antibodies and calibrated with a standard of recombinant GRP78. Serum GRP78 levels increased in alcohol-associated steatohepatitis and alcoholic hepatitis patients correlated with early fibrosis severity (F1 fibrosis stage), but were significantly downregulated in patients with cirrhosis (F4 fibrosis stage). Furthermore, serum GRP78 levels showed a weak negative correlation with liver stiffness measurements (LSM; r = - 0.2064, p = 0.0365) and demonstrated a notable association with the severely advanced fibrotic stage in ALD patients, while showing no significant correlation with the controlled attenuation parameter (CAP) associated with liver steatosis. This study suggests that serum GRP78 is a potential noninvasive biomarker for early liver injury and active fibrogenesis in ALD patients. When combined with LSM, it improves diagnostic accuracy for advanced fibrosis and cirrhosis.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148359810","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":"UBA2: the gatekeeper of the sumoylation pathway and its multifaceted roles in human diseases and therapeutic prospects.","authors":"Yi Liu, Qi Deng, Yang Qu, Minming Yi, Taiqiang Wang, Xuan Li, Rong Zhang, Yongkang Wu","doi":"10.1007/s10238-026-02239-8","DOIUrl":"10.1007/s10238-026-02239-8","url":null,"abstract":"<p><p>Ubiquitin-like modifier-activating enzyme 2 (UBA2), the core catalytic subunit of the ubiquitin-activating enzyme (E1) for the small ubiquitin-like modifier (SUMO)ylation pathway, is the \"gatekeeper\" determining cellular SUMOylation levels. However, a systematic, cross-disease integration of its pathogenic mechanisms and translational value in human diseases is currently lacking. In this review, a disease taxonomy framework was used for the first time to systematically elucidate the multidimensional pathogenic mechanisms of UBA2 in tumors, developmental malformations, autoimmune diseases, and infectious diseases. Research indicates that functional dysregulation of UBA2 is a central node connecting diverse diseases: Driving malignant progression and therapy resistance in tumors, causing congenital malformations during development, acting as a pathogenic factor or autoantigen in autoimmunity, and being targeted by various pathogens for immune evasion. Based on its pivotal role, UBA2 has emerged as an important prognostic biomarker and therapeutic target, with related inhibitors demonstrating promise in preclinical studies. This article further elucidates the strategies and challenges in the clinical translation of precision therapies targeting UBA2, providing a theoretical foundation and translational roadmap.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13582365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148351152","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":"Correction: Single-cell atlas reveals the key role of pro-inflammatory IREB2⁺ microglia subsets in the microenvironment of Alzheimer's disease.","authors":"Wenzheng Rong, Jing Xu, Bo Li, Yapeng Li, Yuming Xu","doi":"10.1007/s10238-026-02238-9","DOIUrl":"10.1007/s10238-026-02238-9","url":null,"abstract":"","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"26 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13310830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148344050","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":"Clonal Metamorphosis: Deconstructing MPN Evolution with Single-Cell and Spatial Multi-Omics.","authors":"Muhammad Shahid Iqbal, Abdullah K Alahmari, Mohd Faiyaz Khan, Sadaf Farooqui, Muhammad Zahid Iqbal, Salah-Ud-Din Khan, Nazia Khan, Vidya Devanathadesikan Seshadri, Amr Ali Mohamed Abdelgawwad El-Sehrawy","doi":"10.1007/s10238-026-02246-9","DOIUrl":"10.1007/s10238-026-02246-9","url":null,"abstract":"<p><p>Myeloproliferative neoplasms (MPNs) present a fundamental paradox: despite sharing a small set of canonical driver mutations in JAK2, CALR, or MPL, patients exhibit striking heterogeneity in disease latency, clinical presentation, and evolutionary trajectories to myelofibrosis or secondary acute myeloid leukemia. This review synthesizes recent advances in single-cell and spatial multi-omic technologies that are resolving this paradox by moving analysis from bulk averages to individual cells and their microenvironmental ecosystems. We examine how targeted single-cell DNA sequencing reconstructs clonal architectures and phylogenies, revealing that driver mutations arise within complex mosaics where mutation order, co-mutation context, and cellular ancestry determine phenotypic outcomes. Integrated single-cell transcriptomic and epigenomic profiling exposes within-clone heterogeneity, lineage biases, and functional states that explain variable penetrance and therapy responses. Spatial transcriptomics, especially when integrated with single-cell transcriptomics, histopathology, and multiplex proteomics, further demonstrates that malignant hematopoietic stem and progenitor cells actively remodel bone marrow niches, creating localized inflammatory and fibrotic microenvironments that select for aggressive subclones. Together, these approaches support a new ecological model of MPN pathogenesis in which early epigenetic hits create permissive stem cell reservoirs, clonal competition and cooperation shape disease progression, and non-cell-autonomous niche and immune signals drive malignant metamorphosis. We discuss how this framework refines prognostication, informs rational combination therapies targeting both malignant cells and their ecosystem, and enables real-time monitoring of clonal dynamics, ultimately charting a course from descriptive atlases to actionable clinical strategies.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13320090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148344063","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 JAK2 mutation: The inflammasome, clonal stability, and the thrombotic niche in myeloproliferative neoplasms.","authors":"Amr Ali Mohamed Abdelgawwad El-Sehrawy, Mutaz Jamal Al-Khreisat, Makhfirat Kibriyeva, Islamova Dilbar, Fotima Axmedova, Jbar Abady Mohammed, Swati Mishra, Navin Kumar Tailor","doi":"10.1007/s10238-026-02247-8","DOIUrl":"10.1007/s10238-026-02247-8","url":null,"abstract":"<p><p>Philadelphia-negative myeloproliferative neoplasms (MPNs) carry a disproportionate thrombotic burden that cannot be explained by conventional cardiovascular risk factors or blood count parameters alone. This review synthesizes emerging evidence positioning MPN-associated thrombosis as a distinct pathobiologic entity, clonal thrombo-inflammation, driven by the convergence of somatic mutations and innate immune activation. We examine the continuum from clonal hematopoiesis of indeterminate potential (CHIP) to overt MPN, highlighting how Janus kinase 2 (JAK2)V617F and other driver mutations reprogram myeloid cells toward hyperinflammatory phenotypes. A recurring mechanistic theme is NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation and interleukin-1 family signaling, which may create a feed-forward loop in which mutant clones amplify inflammatory circuits that, in turn, may enhance clonal fitness and contribute to thrombogenicity across multiple cellular compartments. We propose the 'thrombotic niche' as a conceptual, multi-compartment model encompassing mutant hematopoietic stem cells, hyperinflammatory myeloid effectors, hyperreactive platelets, platelet-leukocyte aggregates, and activated endothelium, but it remains a hypothesis-generating framework that lacks direct prospective clinical validation. Current cytoreductive strategies inadequately address this underlying biology, leaving substantial residual vascular risk. Emerging anti-inflammatory and anti-clonal strategies targeting interleukin-1 beta (IL-1β) (canakinumab), mutant-selective JAK2 inhibition, NLRP3 inflammasome blockade, and P-selectin-mediated adhesion are biologically plausible, but their ability to reduce thrombotic events in MPN remains unproven and should be viewed as hypothesis-generating rather than established clinical benefit. We conclude by outlining a translational research agenda integrating inflammation-aware risk stratification, niche-directed imaging, and spatial multi-omics to guide precision anti-inflammatory interventions in MPN.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13310835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148338062","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":"KIF7 promotes the proliferation of clear cell renal cell carcinoma by activating the WNT/β-catenin signaling pathway.","authors":"Yao Wang, Xiao-Ming Wang, Da Huo, Shi-Bo Wang, Qian-Yi Liu, Jing Pang, Tao Shen, Di Cui, Wen-Juan Zhao, Qing-Feng Luo, Nan Li, Ai-Qun Chen, Ju Cui","doi":"10.1007/s10238-026-02203-6","DOIUrl":"10.1007/s10238-026-02203-6","url":null,"abstract":"<p><p>Aberrant activation of SHH signaling contributes to the progression of multiple malignancies, with KIF7 functioning as a critical mediator that regulates signal transduction from SMO to GLI transcription factors. However, the specific role of KIF7 in ccRCC has not been fully elucidated. In this study, we investigated the expression pattern, prognostic significance, functional role, and potential mechanisms of KIF7 in ccRCC. Analysis of TCGA-KIRC data demonstrated that KIF7 expression was significantly elevated in tumor tissues compared with adjacent normal tissues. High KIF7 expression was strongly associated with advanced pathological stage and poor overall survival. IHC performed on commercial tissue microarrays further confirmed increased KIF7 protein levels in ccRCC samples. Functional experiments in the 786-O cell line revealed that KIF7 overexpression markedly enhanced cell proliferation. Mechanistically, KIF7 overexpression activated the Wnt/β-catenin signaling pathway and upregulated downstream cell cycle regulators, including c-Myc and c-Jun. KIF7 expression was positively correlated with infiltration of CD4 + T cells, macrophages, and neutrophils. Moreover, it showed significant positive associations with immune checkpoint molecules PDCD1 and CD160. GSCA/GDSC-based drug sensitivity prediction suggested that high KIF7 expression was associated with increased predicted sensitivity to docetaxel and bleomycin, whereas no significant association was observed for I-BET-762. In conclusion, KIF7 plays a tumor-promoting role in ccRCC by enhancing proliferation, activating Wnt/β-catenin signaling. Additionally, it was associated with shaping the immune microenvironment. These findings highlight KIF7 as a potential prognostic biomarker and therapeutic target in ccRCC.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13331826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148344100","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":"Identifying coagulation-related biomarkers in steroid-induced osteonecrosis of the femoral head: implications for early diagnosis and treatment.","authors":"Congqin Xie, Jian Du, Zhi Liu, Yanlei Lv, Huaijun Ni, Fangyuan Yu","doi":"10.1007/s10238-026-02245-w","DOIUrl":"10.1007/s10238-026-02245-w","url":null,"abstract":"<p><p>Steroid-induced osteonecrosis of the femoral head (SONFH) is closely associated with coagulation dysfunction, but its molecular mechanisms remain incompletely understood. This study aimed to identify coagulation-related biomarkers for SONFH and evaluate their diagnostic relevance. The GSE123568 dataset from the Gene Expression Omnibus database (GEO) was analyzed, and differentially expressed genes (DEGs) were intersected with coagulation-related genes (CRGs) from the Molecular Signatures Database to identify coagulation-related differentially expressed genes (CRDEGs). Functional enrichment analysis was performed to explore the biological processes and pathways associated with these genes, while protein-protein interaction network analysis and three machine learning algorithms were applied to identify key genes. A nomogram model was constructed and evaluated using bootstrap internal validation. Gene set enrichment analysis, single-sample gene set enrichment analysis, competing endogenous RNA network, and Drug Signature Database analyses were performed to explore potential regulatory mechanisms. The expression levels of the key genes were preliminarily assessed by reverse transcription quantitative polymerase chain reaction (RT-qPCR). In total, 49 CRDEGs were identified and were mainly enriched in immune response, blood coagulation, and complement and coagulation cascades. PECAM1, LGALS3, and ANXA5 were identified as key genes. The prediction model constructed based on these genes showed favorable diagnostic discrimination, with a bootstrap AUC of 0.939 (95% CI: 0.840-0.977). RT-qPCR showed decreased PECAM1 and LGALS3 expression and increased ANXA5 expression in SONFH patients. These findings suggest that PECAM1, LGALS3, and ANXA5 may serve as potential coagulation-related biomarkers for SONFH, providing a basis for further clinical validation and mechanistic investigation.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13574886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148344109","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}