Clinical and Experimental Medicine最新文献

{"title":"Decoding chromatin regulator-LAIR1⁺ M2 like macrophage patterns in atherosclerosis and clinical outcomes of Lung adenocarcinoma patients: evidence from artificial intelligence-driven multi omics and in vitro validation.","authors":"Chuanqi Zhang, Bo Chen, Zhe Li, Xianwei Li, Weiliang Jiang","doi":"10.1007/s10238-026-02217-0","DOIUrl":"10.1007/s10238-026-02217-0","url":null,"abstract":"<p><p>Atherosclerosis (AS) is a common complication of lung adenocarcinoma (LUAD), but its underlying mechanisms in LUAD remain unclear. This study aimed to decipher the role of chromatin regulators in AS pathogenesis and their association with clinical outcomes in LUAD patients. AS- and chromatin regulator (CR)-associated prognostic indicators were identified in LUAD and analyzed in the TCGA-LUAD cohort using Cox regression and Disease Ontology analysis. CR-related risk subgroups were defined by NMF in the GSE26939 cohort. GSVA and WGCNA, combined with interpretable machine learning, were used to construct a predictive model and identify key genes, which were validated in GSE68465. The molecular features of key genes and their roles in AS were further evaluated. Besides, mechanisms of key genes in M2-like macrophages were assessed at the single-cell level in LUAD patients using cutting-edge analytical frameworks. A deep learning framework and molecular docking were used to screen natural compounds. Finally, co-culture experiments were conducted for validation. CR signatures can guide the LUAD patients LUAD patients into high- and low-AS risk groups and were associated with clinical outcomes. LAIR1 can be considered as an AS-related factor enriched in M2-like macrophages and involved in LUAD progression. Quercetin was identified as potential preventive agent for AS in LUAD patients. CR-associated signatures play an important role in AS pathogenesis and LUAD progression.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13526722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148276494","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":"Engineered small extracellular vesicles in hematologic malignancies: mechanisms, therapeutic strategies, and translational challenges.","authors":"Chou-Yi Hsu, Saidmurodkhon Murtazaev, Sally Hassan Zubair, Mohammad Abohassan, Pareshkumar N Patel, Gunjan Singh, Vimal Arora, Priya Priyadarshini Nayak, Muhammad Shahid Iqbal, Zahraa Khudhair Abbas","doi":"10.1007/s10238-026-02216-1","DOIUrl":"10.1007/s10238-026-02216-1","url":null,"abstract":"<p><p>Hematologic malignancies remain among the most challenging cancers to treat due to genetic heterogeneity, clonal evolution, and therapy resistance. Extracellular vesicles (EVs), particularly small EV (sEV)-enriched populations, have emerged as active mediators of disease biology, contributing to tumor progression, immune evasion, and chemoresistance through intercellular transfer of bioactive cargo. Recent advances in EV engineering have repositioned these vesicles as programmable delivery platforms capable of transporting nucleic acids, proteins, and chemotherapeutic agents with improved targeting potential. Preclinical studies across multiple hematologic models demonstrate that engineered EVs can induce immune activation, modulate oncogenic signaling pathways, and partially overcome drug resistance. However, these findings remain largely confined to experimental settings, with limited standardization of loading efficiency, biodistribution, and functional potency. Clinically, EV-based applications in hematology are still at an early stage, with most studies focused on biomarker discovery and supportive therapies rather than direct antitumor interventions. In parallel, theranostic EV platforms and liquid biopsy approaches offer promising opportunities for minimally invasive disease monitoring, although their clinical validation remains incomplete. Artificial intelligence (AI) further enhances this field by enabling advanced biomarker analysis and guiding cargo design and targeting strategies, yet its therapeutic applications are still largely exploratory. Despite key challenges, including vesicle heterogeneity, donor variability, suboptimal cargo loading, and manufacturing constraints, these limitations are primarily technical and may be addressed through standardization and engineering optimization. Collectively, EV-based systems represent a promising but still maturing platform with the potential to contribute to next-generation precision oncology in hematologic malignancies.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13385246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148270502","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":"Absence of osteoclastogenic response to pooled polyclonal anti-citrullinated peptide/protein antibodies from patients with rheumatoid arthritis in vitro.","authors":"Xiaoli Chen, Zhuo An, Changhong Li, Jinxia Zhao","doi":"10.1007/s10238-026-02208-1","DOIUrl":"10.1007/s10238-026-02208-1","url":null,"abstract":"<p><p>Anti-citrullinated peptide/protein antibodies (ACPAs) are specific serological markers for rheumatoid arthritis (RA), but their direct role in promoting osteoclastogenesis remains controversial. This study aims to determine whether polyclonal ACPAs purified from RA patients can directly drive osteoclastogenesis in vitro. Polyclonal ACPAs were purified from pooled sera of 37 ACPA positive RA patients using Protein G and multi-citrullinated-epitope peptide (MCEP) conjugated affinity chromatography, with control IgG from 10 ACPA negative RA patients and a healthy donor. The purity and specific binding capability to citrullinated vimentin were verified by Coomassie Blue staining and western blot. CD14 + monocytes from healthy donors and RA patients were induced to differentiate into osteoclasts with M-CSF and RANKL, in the presence or absence of ACPAs. Osteoclast formation was evaluated by tartrate resistant acid phosphatase (TRAP) staining, gene expression of osteoclast-specific markers (TRAP, cathepsin K, MMP9) by quantitative PCR, and bone resorption activity by scanning electron microscopy. The purified ACPAs showed intact IgG structure of heavy and light chains, and specific binding to citrullinated vimentin, but not to native vimentin. However, ACPAs treatment did not significantly increase the number of TRAP-positive multinucleated cells, the expression of osteoclast-related genes, or bone resorption pit area compared to controls. Our findings demonstrate that pooled polyclonal ACPAs from RA patients, purified by MCEP affinity chromatography, do not directly promote osteoclastogenesis in vitro, suggesting that their osteoclastogenic effects may require a more complex microenvironment or depend on specific antibody properties not captured in this experimental setting.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13526721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148263703","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":"IL10 promotes surgical incision healing in sepsis by regulating PI16⁺ fibroblasts and CCL8⁺ macrophages.","authors":"Xiaojun He, Cheng Xu, Yan Zou, Wei Wang, Liwei Wu, Quanhong Zhou","doi":"10.1007/s10238-026-02210-7","DOIUrl":"10.1007/s10238-026-02210-7","url":null,"abstract":"<p><p>Sepsis severely impairs surgical incision healing, but the underlying mechanisms and effective interventions remain insufficiently understood. Interleukin-10 (IL10) exerts potent anti-inflammatory activity, yet its role in regulating fibroblast and macrophage dynamics during septic wound repair is unclear. Human peri-incisional skin specimens were collected from septic and non-septic patients. A lipopolysaccharide (LPS)-induced sepsis mouse model with surgical incision was established, followed by IL10 treatment. Single-cell RNA sequencing, cell trajectory analysis, cell-cell communication analysis, gene set variation analysis, and immunofluorescence were used to investigate cellular and molecular alterations. Only mouse samples were used for single-cell sequencing in this study. Single-cell analysis identified 8 cell types, including 3 non-immune cell types and 5 immune cell types. Sepsis increased NK cells and macrophages, and upregulated PI16⁺ fibroblasts and CCL8⁺ macrophages in wound tissue. IL10 treatment elevated mast cells, T cells, and neutrophils, downregulated peptidase inhibitor 16 (Pi16) and chemokine ligand 8 (Ccl8) expression, and attenuated fibroblast-macrophage crosstalk. Mechanistically, IL10 promoted fibroblast proliferation by inducing macrophages to secrete Il1b and Osm. Sepsis delays surgical incision healing via upregulating PI16⁺ fibroblasts and CCL8⁺ macrophages and enhancing inflammatory cell crosstalk. IL10 accelerates wound repair by suppressing these detrimental subsets and activating Il1b/Osm-mediated fibroblast proliferation. PI16 and CCL8 may serve as potential therapeutic targets for septic wound healing.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13526718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148270558","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":"Zinc supplementation ameliorates colitis in mice by sensitizing pathogenic CD4⁺ T cells to ferroptosis.","authors":"Zongkuo Li, Jianting Cai","doi":"10.1007/s10238-026-02192-6","DOIUrl":"10.1007/s10238-026-02192-6","url":null,"abstract":"<p><p>Inflammatory Bowel Disease (IBD) is driven by the hyperactivation of pathogenic Th1 and Th17 subsets. Although clinical zinc deficiency strongly correlates with severe IBD outcomes, the precise immunomodulatory mechanisms underlying this association remain unknown. To systematically investigate the role of zinc in CD4⁺ T cell fate determination and intestinal homeostasis, we evaluated its immunomodulatory dynamics using a murine colitis model alongside in vitro differentiation assays employing human primary naive CD4⁺ T cells. We found that zinc supplementation remarkably ameliorated experimental mucosal damage by abruptly halting the local infiltration of pathogenic CD4⁺ T cells. Both in vivo and in vitro analyses revealed that zinc does not merely stall T cell polarization, but actively sensitizes these effector subsets to cell demise. Comprehensive transcriptomic sequencing pinpointed the ferroptosis cascade as the critical mediator of this clearance mechanism. Specifically, zinc systematically suppressed T cell anti-ferroptotic defenses by downregulating GPX4 and SLC7A11, while concurrently amplifying pro-ferroptotic drivers such as ACSL4. This targeted metabolic stress profoundly sensitized hyperactive T cells to ferroptosis, effectively purging the inflammatory mucosal niche. Ultimately, these findings reframe the fundamental role of zinc in intestinal immune homeostasis, exposing ferroptosis as a druggable vulnerability in IBD and providing a strong mechanistic rationale for zinc-based clinical interventions.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13490243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148270512","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":"Dissecting PCD-driven molecular landscapes in AML: a multi-omic framework for prognostication and therapeutic targeting.","authors":"Jing Liu, Fangmin Zhong, Xiaozhong Wang, Liuqing Xu, Zanwei Tu, Xiaofang Cheng, Linlin Zhang, Guangyao Kong","doi":"10.1007/s10238-026-02205-4","DOIUrl":"10.1007/s10238-026-02205-4","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) remains a molecularly heterogeneous malignancy with poor prognosis, necessitating robust biomarkers for risk stratification. By integrating single-cell RNA-seq and multiomics data from 2,680 AML samples across 10 cohorts, we demonstrate that dysregulated programmed cell death (PCD) pathways are significantly elevated in AML cells and correlate with adverse outcomes. Unsupervised clustering identified two PCD-driven subtypes: Subtype A exhibits high PCD activity, an immunosuppressive microenvironment (M2 macrophages, upregulated PD-L1/HAVCR2), increased somatic mutations (NPM1/DNMT3A/FLT3), and poor survival, while Subtype B shows lower PCD activity, immune-active features, and better prognosis. As an exploratory analysis, subtype-specific therapeutic vulnerabilities were revealed: Subtype A displays predicted sensitivity to immune checkpoint inhibitors (anti-PD-1) and tipifarnib, whereas Subtype B responds better to cytarabine/doxorubicin. We developed PCDRScore-a prognostic model incorporating 13 PCD-related genes via machine learning-which outperformed existing models (higher C-index) in 10 validation cohorts and remained independent of clinicopathological factors. A nomogram combining PCDRScore, age, and cytogenetic risk enhanced clinical applicability. Crucially, experimental validation confirmed significant upregulation of key model genes (HIP1, SQLE, VNN1) in AML patient samples and cell lines (P < 0.05), reinforcing the model's biological relevance. These findings establish PCD dysregulation as a central axis of AML heterogeneity, providing a framework for precision risk stratification and hypothesis-generating immunophenotype-guided therapy.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13500440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148249531","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":"PYCR1 promotes glutamine metabolism and the progression of lung adenocarcinoma by regulating the expression of OPLAH.","authors":"Wei Chen, Kai Wang, Renyu Wang, Xufeng Deng, Xiaobing Liu, Peng Dai, Quanxing Liu","doi":"10.1007/s10238-026-02181-9","DOIUrl":"10.1007/s10238-026-02181-9","url":null,"abstract":"<p><p>Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer. Glutamine plays a critical role in the progression of LUAD. However, the function of pyrroline-5-carboxylate reductase 1 (PYCR1) and its regulatory role in glutamine metabolism remain unclear. Transcriptomic and clinical data for LUAD were obtained from The Cancer Genome Atlas (TCGA) and validated using Gene Expression Omnibus (GEO) datasets (GSE19188, GSE13213). Glutamine metabolism-related genes were analyzed for differential expression and prognostic significance. Functional enrichment was performed via gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analyses. Single-cell RNA-seq data (GSE117570) were processed using Seurat, and cell-cell communication was inferred with CellChat. In vitro, lentiviral overexpression, Western blotting, EdU, CCK-8, and glutamine uptake assays were conducted. An orthotopic xenograft model was established in nude mice to assess tumor growth in vivo. Six glutamine-metabolism-related genes were found significantly overexpressed in LUAD tissues and associated with poor overall survival. Single-cell sequencing revealed predominant PYCR1 expression in malignant cells. Functional assays demonstrated that PYCR1 overexpression enhanced glutamine uptake, proliferation, and inhibited apoptosis in LUAD cells, effects mediated via suppression of the P53 pathway. PYCR1 promoted tumor growth in a xenograft model and was found to transcriptionally upregulate 5-oxoprolinase (OPLAH), which augmented its oncogenic effects. Our findings identify the PYCR1/OPLAH axis as a key driver of LUAD progression via p53 signaling, revealing a promising therapeutic target.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13562194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148249559","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":"ALKBH2 promotes the Warburg effect and bladder cancer progression under hypoxic conditions via the PI3K/AKT pathway.","authors":"Zhangjie Yang, Jinhu Ma, Ziyang Qiang, Wenhao Xie, Liang Jiao, Zhenxing Hu, Tiange Zhang, Limei Zhang, Jinqiong Lv, Fangqian Yue, Guojun Chen","doi":"10.1007/s10238-026-02212-5","DOIUrl":"10.1007/s10238-026-02212-5","url":null,"abstract":"<p><p>Emerging evidence links DNA repair enzymes to metabolic reprogramming in cancer. ALKBH2 safeguards genomic integrity by reversing alkylation damage, yet its potential role beyond repair-specifically in modulating the Warburg effect-remains unexplored in bladder cancer. While implicated in digestive tract malignancies, ALKBH2's function in urothelial carcinoma is unknown. Investigating this gap may reveal ALKBH2 as a novel metabolic driver in bladder cancer progression. ALKBH2 expression was analyzed in bladder cancer tissues and matched adjacent normal tissues by qPCR, Western blotting, and immunofluorescence (IF). Hematoxylin and eosin (H&E) staining was used to confirm tissue histology. Using stable ALKBH2-overexpressing and knockdown bladder cancer cell lines, we systematically assessed the effects of ALKBH2 on tumor cell behavior in vitro and tumor growth in vivo. Moreover, its involvement in hypoxia-associated Warburg metabolic reprogramming was investigated under 1% O₂. In vitro, ALKBH2 overexpression enhanced bladder cancer cell proliferation, migration, invasion, and clonogenicity, whereas ALKBH2 knockdown exerted opposite effects. Consistently, in vivo xenograft models demonstrated that silencing ALKBH2 significantly suppressed tumor growth. Mechanistic investigations revealed that ALKBH2 functions as an m6A demethylase to reduce PTEN mRNA stability, thereby activates the PI3K/AKT signaling pathway under hypoxic conditions, as evidenced by increased pathway activation, thereby facilitating metabolic reprogramming and tumor cell progression. These findings suggest that ALKBH2 plays a critical oncogenic role in bladder cancer by regulating PI3K/AKT pathway activation and promoting the Warburg effect, highlighting its potential as a therapeutic target for bladder cancer.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13500419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148249598","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 PLAU as a shared pathogenic gene in type 2 diabetes and bladder urothelial carcinoma through integrated transcriptomic analysis and machine learning for diagnostic and therapeutic value.","authors":"Shiyong Xin, Guanyu Li, Xingqiang Yang, Junjie Su, Ruixin Li, Wang Qin, Zheng Zhang, Chu Wang, Yingao Zhu, Liming Feng, Sichang Ren, Zhongwei Gao","doi":"10.1007/s10238-026-02211-6","DOIUrl":"10.1007/s10238-026-02211-6","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Type 2 diabetes mellitus (T2DM) and bladder urothelial carcinoma (BLCA) are two kinds of diseases that seriously threaten human health. Their pathogenesis is complex and involves the interaction of multiple genes and multiple pathways. Recent epidemiological studies have shown that the risk of BLCA in patients with T2DM is significantly higher than that in non-diabetic people, suggesting that there may be a potential biological correlation between the two. Genomic studies have opened up new ways to reveal the common genetic characteristics of T2DM and BLCA. However, most of the current studies only focus on a single disease, and the comorbidity mechanism of these two diseases still needs to be further explored. Firstly, the datasets of BLCA and T2DM were downloaded from the The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases respectively. Differential expression genes (DEGs) were identified using the Limma package. Weighted gene co-expression network analysis (WGCNA) was employed to determine the co-expression modules related to BLCA and T2DM, and the common potential target genes were obtained. Correlation analysis and enrichment analysis were conducted on these target genes. Then, the best diagnostic biomarker - plasminogen activator (PLAU) was selected using machine learning algorithms. Additionally, the role of PLAU in the progression of T2DM and BLCA was confirmed through immunohistochemistry, Western Blot, and Edu experiments. Finally, small molecule compounds targeting PLAU were discovered through molecular docking and virtual screening, and the inhibitory effect of these small molecules on the progression of bladder urothelial carcinoma was verified through experiments. This study conducted a combined limma and WGCNA analysis on the T2DM and BLCA datasets to identify 42 common potential target genes, which were enriched in pathways such as innate immunity. Using machine learning algorithms such as LASSO and SVM, PLAU was identified as the best diagnostic marker for T2DM combined with BLCA. It was significantly highly expressed in both T2DM and BLCA samples, and high expression of PLAU predicted a shorter overall survival period for BLCA patients. Experimental results confirmed that PLAU was highly expressed in BLCA tissues and increased with the severity of malignancy. Knockdown (sh-PLAU) of PLAU could inhibit cancer cell proliferation and migration in a high-glucose environment, while overexpression (oe-PLAU) still promoted cancer cell progression in a low-glucose environment. Finally, molecular docking virtual screening revealed that the small molecule compound epigallocatechin gallate (EGCG) could target and inhibit PLAU, and effectively inhibited the proliferation and invasion of BLCA cells in experiments. The results of this study reveal the role of PLAU, a common characteristic gene of T2DM and BLCA, whose high expression drives tumor progression and poor prognosis. Moreover, small molecule drugs targeti","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13478037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148216691","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":"Thromboembolic risk in subcutaneous versus intravenous immunoglobulin therapy: a systematic review and narrative meta-synthesis.","authors":"Shihshuan Fang, Yu-Chieh Chen, Shenghan Chen","doi":"10.1007/s10238-026-02207-2","DOIUrl":"10.1007/s10238-026-02207-2","url":null,"abstract":"<p><p>Intravenous immunoglobulin (IVIg) therapy is associated with thromboembolic complications, including deep vein thrombosis (DVT), pulmonary embolism (PE), ischaemic stroke, and myocardial infarction (MI). Subcutaneous immunoglobulin (SCIg) achieves lower peak serum IgG concentrations and may confer a reduced thromboembolic risk. We systematically reviewed the comparative thromboembolic safety of SCIg versus IVIg across neurological and immunological indications. We searched PubMed, Embase, Cochrane Library, Web of Science, Scopus, and ClinicalTrials.gov from inception to December 2024. Studies reporting thromboembolic events in patients receiving IVIg or SCIg for any indication were eligible. Two reviewers independently screened, extracted data, and assessed risk of bias. Where feasible, pooled incidence rates with 95% confidence intervals (CIs) were calculated using Freeman-Tukey double arcsine transformation. Thirty-four studies (approximately 12,800 patient-years of immunoglobulin exposure) were included. IVIg-treated patients (approximately 10,600 patient-years across 27 studies) experienced thromboembolic events at a pooled incidence of 1.8 per 100 patient-years (95% CI: 0.9-3.1). SCIg-treated patients (approximately 2,200 patient-years across 7 studies) had a pooled incidence of 0.14 per 100 patient-years (95% CI: 0.01-0.52). Only 3 thromboembolic events were documented in SCIg cohorts, all in patients with pre-existing prothrombotic risk factors. No head-to-head randomised trial comparing thromboembolic outcomes between routes exists. GRADE certainty was very low for the comparative estimate. Indirect evidence suggests that SCIg may be associated with a lower thromboembolic risk than IVIg, consistent with pharmacokinetic predictions. However, substantial differences in patient populations, follow-up duration, and event ascertainment between SCIg and IVIg cohorts preclude definitive conclusions. Prospective comparative trials with pre-specified thromboembolic endpoints are needed.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13478024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148216715","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}