Clinical and Experimental Medicine最新文献

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HCQ reverses the immune imbalance related to severe infections following chemotherapy of acute myeloid leukemia and exhibits inhibitory effects on inflammatory cytokine storms. HCQ逆转急性髓系白血病化疗后严重感染相关的免疫失衡,并对炎症细胞因子风暴表现出抑制作用。
IF 3.5 4区 医学
Clinical and Experimental Medicine Pub Date : 2025-08-15 DOI: 10.1007/s10238-025-01833-6
Yanquan Liu, Hehui Zhang, Qinglin Xu, Zuotao Li, Huidong Guo, Huanwen Tang
{"title":"HCQ reverses the immune imbalance related to severe infections following chemotherapy of acute myeloid leukemia and exhibits inhibitory effects on inflammatory cytokine storms.","authors":"Yanquan Liu, Hehui Zhang, Qinglin Xu, Zuotao Li, Huidong Guo, Huanwen Tang","doi":"10.1007/s10238-025-01833-6","DOIUrl":"10.1007/s10238-025-01833-6","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is the most prevalent hematological malignancy in adults, characterized by a rapid progression, short clinical course, and poor prognosis. Immune imbalance following severe infections post-chemotherapy represents a critical cause of mortality in AML patients. Our study investigates the effects of hydroxychloroquine (HCQ) on immune imbalance in severe infections after AML chemotherapy and its mechanisms of action on mononuclear macrophage activation and inflammatory cytokine storm models. The findings are expected to provide significant practical implications for both basic research and clinical interventions in managing severe infections in leukemia patients. Our findings indicated that some specific chemokines and cytokines exhibited abnormal increases in AML patients, with more pronounced elevations in severely infected AML patients (AML-SI) compared to uninfected counterparts. HCQ inhibited leukemic cell proliferation and induced apoptosis, although low concentrations demonstrated minimal cytotoxicity. Co-culture of THP-1 cells with bone marrow-derived mesenchymal stem cells (BM-MSCs) from AML patients significantly increased IL-6, IL-8, and TNF-α levels, which were markedly reduced upon HCQ intervention. HCQ exerted limited effects on the CXCL12-CXCR4/7 regulatory axis but induced programmed cell death of leukemic THP-1 cells. RNA-seq showed that the differentially expressed genes in HCQ intervention group were mainly enriched in NOD-like receptor signaling pathway, chemokine signaling pathway, IL-17 signaling pathway, PPAR signaling pathway, NF-κB signaling pathway, and TGF-β signaling pathway. Furthermore, HCQ suppressed monocyte proliferation, enhanced apoptosis, and demonstrated stronger effects on activated mononuclear macrophages. Mechanistically, HCQ regulated Bcl-2 family protein expression, upregulated Bax, activated Caspase-3, and inhibited NLRP3/IL-17A and TLR4/NF-κB signaling pathways, thereby suppressing inflammatory cytokine storms. In all, HCQ effectively reverses immune imbalance and suppresses malignant biological characteristics of leukemic cells, and it also attenuates inflammatory cytokine storms by inhibiting chemokine regulatory axes and suppressing NLRP3/IL-17A and TLR4/NF-κB signaling pathways, offering promising potential for basic research and clinical applications in inflammatory cytokine storm management.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"294"},"PeriodicalIF":3.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12356743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854780","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}
引用次数: 0
Development and external validation of a predictive model for lung metastases in kidney cancer based on clinical and laboratory features. 基于临床和实验室特征的肾癌肺转移预测模型的开发和外部验证。
IF 3.5 4区 医学
Clinical and Experimental Medicine Pub Date : 2025-08-14 DOI: 10.1007/s10238-025-01839-0
Zhi Shang, Ruonan Tan, Cong Wei, Zhe Hong, Dingwei Ye
{"title":"Development and external validation of a predictive model for lung metastases in kidney cancer based on clinical and laboratory features.","authors":"Zhi Shang, Ruonan Tan, Cong Wei, Zhe Hong, Dingwei Ye","doi":"10.1007/s10238-025-01839-0","DOIUrl":"10.1007/s10238-025-01839-0","url":null,"abstract":"<p><strong>Background: </strong>Lung metastases (LMs) are common and clinically significant in kidney cancer, contributing to poor prognosis and limited treatment response. Early detection of patients at high risk for LMs is crucial for developing personalized treatment strategies.</p><p><strong>Methods: </strong>This retrospective study included 2652 patients with kidney cancer, pathologically confirmed, from two medical centers between 2000 and 2020. A training cohort (n = 1500) was used to develop a predictive model for LMs based on clinical, pathological, and laboratory variables. Multivariate logistic regression was applied to identify independent predictors, and a nomogram was constructed. Model performance was evaluated using receiver operating characteristic (ROC) curves, calibration plots, probability density functions (PDFs), and decision curve analysis (DCA). An external validation cohort (n = 1152) was used to assess generalizability.</p><p><strong>Results: </strong>Family cancer history, advanced T stage, and N nodal stage were identified as independent predictors of LMs. The nomogram demonstrated excellent discrimination in the training cohort (AUC = 0.938) and moderate performance in the validation cohort (AUC = 0.883), outperforming individual variables. Calibration analysis showed good agreement between predicted and observed probabilities. Patients with LMs had significantly worse overall survival than those without (p < 0.001). DCA validated the nomogram's greater clinical value over treat-all or treat-none approaches.</p><p><strong>Conclusion: </strong>This nomogram-based model offers an efficient and accessible tool for the early detection of kidney cancer patients at risk for LMs. It enables individualized risk stratification and may assist in optimizing clinical decision-making and improving patient outcomes. Further prospective validation is warranted.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"293"},"PeriodicalIF":3.5,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12354624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854779","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}
引用次数: 0
The expression of CD109 in B-cell acute lymphoblastic leukemia and its potential as a promising marker for minimal residual disease (MRD) detection. CD109在b细胞急性淋巴细胞白血病中的表达及其作为微量残留病(MRD)检测标志物的潜力
IF 3.5 4区 医学
Clinical and Experimental Medicine Pub Date : 2025-08-14 DOI: 10.1007/s10238-025-01823-8
Zhifang Xu, Shaotong Dong, Yi Chen, Lixia Wang, Fanggang Ren, Yunxia Wang, Xiaojuan Wang, Dan Liu, Bianbian Qiao, Ju Deng, Yingxia Gu, Kai Dong, Yaofang Zhang, Jianmei Chang, Hongwei Wang
{"title":"The expression of CD109 in B-cell acute lymphoblastic leukemia and its potential as a promising marker for minimal residual disease (MRD) detection.","authors":"Zhifang Xu, Shaotong Dong, Yi Chen, Lixia Wang, Fanggang Ren, Yunxia Wang, Xiaojuan Wang, Dan Liu, Bianbian Qiao, Ju Deng, Yingxia Gu, Kai Dong, Yaofang Zhang, Jianmei Chang, Hongwei Wang","doi":"10.1007/s10238-025-01823-8","DOIUrl":"10.1007/s10238-025-01823-8","url":null,"abstract":"<p><strong>Background: </strong>CD109 is overexpressed in various tumors, but its role in hematologic malignancies, particularly acute B lymphoblastic leukemia (B-ALL), remains unclear.</p><p><strong>Methods: </strong>CD109 expression was assessed at both mRNA and protein levels in B-ALL patients using real-time quantitative PCR (RQ-PCR) and multiparameter flow cytometry (MFC). The relationship between CD109 expression and clinical and laboratory parameters was examined. The potential of CD109 as a marker for minimal residual disease (MRD) detection was evaluated. Functional studies were conducted in leukemia cell lines.</p><p><strong>Results: </strong>CD109 mRNA was significantly upregulated in newly diagnosed and relapsed B-ALL patients compared to healthy controls and remission cases. MFC revealed CD109 positivity in 79.0% B-ALL patients, with higher rates in relapsed cases (85.7%) and CD34 + B-ALL patients. CD109 expression was minimal in mature B cells and precursors B cell. CD109 expression remained stable across disease phases including diagnosis, MRD positivity, and relapse. Functional assays demonstrated that CD109-positive Nalm6 cells exhibited significantly increased proliferative and invasive abilities.</p><p><strong>Conclusion: </strong>CD109 is upregulated in B-ALL and promotes leukemia cell proliferation and migration. Its consistent expression across disease stages suggests it may be a promising marker for MRD detection, highlighting its clinical significance in leukemia management.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"292"},"PeriodicalIF":3.5,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12354559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854781","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}
引用次数: 0
Metabolic reprogramming of arachidonic acid in clear cell renal carcinoma promotes an immunosuppressive microenvironment by activating MDK signaling pathway. 透明细胞肾癌中花生四烯酸的代谢重编程通过激活MDK信号通路促进免疫抑制微环境。
IF 3.5 4区 医学
Clinical and Experimental Medicine Pub Date : 2025-08-13 DOI: 10.1007/s10238-025-01807-8
Jiaxi Yao, Tong Xu, Chenyuan Wang, Junfeng Xie, Qing Jiang
{"title":"Metabolic reprogramming of arachidonic acid in clear cell renal carcinoma promotes an immunosuppressive microenvironment by activating MDK signaling pathway.","authors":"Jiaxi Yao, Tong Xu, Chenyuan Wang, Junfeng Xie, Qing Jiang","doi":"10.1007/s10238-025-01807-8","DOIUrl":"10.1007/s10238-025-01807-8","url":null,"abstract":"<p><p>Metabolic reprogramming is a key feature of clear cell renal cell carcinoma (ccRCC), and metabolic abnormality can lead to significant changes in gene expression, resulting in the immunosuppressive microenvironment. In this study, we used a combination of single-cell RNA sequencing and bulk RNA sequencing to investigate the relationships between ccRCC metabolic reprogramming and immune exhaustion. Metabolic subtypes of ccRCC patients were constructed using bulk RNA sequencing. Tumor cells of different metabolic subtypes were analyzed and extracted by the Scissor algorithm, using single-cell RNA sequencing. The molecular mechanisms of abnormal metabolic regulating tumor immunity were explored using cell-cell communication analysis. In addition, the correlations between relevant molecules and immune exhaustion signals were verified in ccRCC by immunohistochemistry. The molecular mechanisms of metabolic abnormalities leading to immune exhaustion were validated via Western blotting, ELISA, cell co-culture and immunotherapy models. ccRCC patients can be divided into MT1 and MT2 metabolic subtypes. The MT2 subtype has a poorer prognosis and lower response to immunotherapy. Abnormal metabolism of arachidonic acid is a prominent feature of the MT2 subtype, and activates the MDK signaling pathway. As a secreted protein, MDK can further recruit immunosuppressive cells, such as Treg, Tex, and TAM. Blocking the arachidonic acid COX metabolic pathway significantly reduces the expression and secretion levels of MDK, thereby reprogramming the tumor microenvironment to promote anti-tumor immunity. Abnormal metabolism of arachidonic acid plays an important role in promoting immune exhaustion by activating the MDK signaling pathway. MDK may serve as an important biomarker for predicting the immune therapy response in ccRCC. By reducing MDK secretion, targeting blockade of arachidonic acid metabolism may be an effective treatment strategy to enhance the efficacy of immunotherapy in ccRCC.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"291"},"PeriodicalIF":3.5,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12350486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144834312","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}
引用次数: 0
Unlocking the therapeutic potential of the STING signaling pathway in anti-tumor treatment. 揭示STING信号通路在抗肿瘤治疗中的治疗潜力。
IF 3.5 4区 医学
Clinical and Experimental Medicine Pub Date : 2025-08-12 DOI: 10.1007/s10238-025-01838-1
Jinghui Li, Haoqiang Yang, Meiling Zhu, Pengyu Zhang, Yang Liu, Yiting Niu, Tao Zhou, Yanjun Li
{"title":"Unlocking the therapeutic potential of the STING signaling pathway in anti-tumor treatment.","authors":"Jinghui Li, Haoqiang Yang, Meiling Zhu, Pengyu Zhang, Yang Liu, Yiting Niu, Tao Zhou, Yanjun Li","doi":"10.1007/s10238-025-01838-1","DOIUrl":"10.1007/s10238-025-01838-1","url":null,"abstract":"<p><p>The STING signaling pathway, as a core hub connecting innate immunity and adaptive immunity, plays a complex and dynamic dual role in tumor immune regulation. This review systematically explains the multi-dimensional mechanism of this pathway in tumor occurrence and development: On the one hand, it builds a multi-level anti-tumor immune response network by activating the antigen presentation function of dendritic cells (DCs), enhancing the stemness maintenance of CD8⁺ T cells and the cytotoxic effect of natural killer cells (NK cells); on the other hand, it forms a bidirectional regulation with the malignant transformation process of tumors (such as epithelial-mesenchymal transition (EMT), angiogenesis, and metabolic reprogramming), and its direction of action highly depends on the spatiotemporal specificity of the tumor microenvironment and the level of genomic instability. Research reveals that the anti-tumor efficacy of the STING pathway is precisely regulated by the intensity of DNA damage response (DDR), mitochondrial stress state, and epigenetic regulatory network (such as the yes-associated protein/transcriptional coactivator with PDZ-binding motif-protein phosphatase 2A catalytic subunit (YAP/TAZ-PP2Ac) axis, which provides a molecular basis for the development of precise intervention strategies. Current combined treatment strategies have broken through the limitation of single-target, achieving multi-level synergy from molecular intervention to system regulation through the sequential coordination of immune checkpoint inhibitors and STING agonists, the positive feedback loop of DNA damage induced by radiotherapy (RT)/chemotherapy and innate immune activation, and tumor metabolic-immune reprogramming mediated by nanocarriers. Notably, STING activation may induce the compensatory upregulation of immune suppressive factors such as interleukin-35 (IL-35)/programmed cell death 1 ligand 1 (PD-L1), and stratified treatment strategies based on tumor heterogeneity characteristics will become the key to overcoming drug resistance. This article not only constructs a theoretical framework of \"immune initiation-microenvironment remodeling-malignant transformation inhibition\" in a trinity, but also marks the paradigm shift of tumor immunotherapy from single-pathway activation to multi-scale dynamic regulation, providing a route map that is both innovative and feasible for clinical translation.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"290"},"PeriodicalIF":3.5,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12343656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820745","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}
引用次数: 0
A national, multicenter, retrospective study of human immunodeficiency virus infection-associated lymphoma in China. 中国人类免疫缺陷病毒感染相关淋巴瘤的一项全国性、多中心、回顾性研究
IF 3.5 4区 医学
Clinical and Experimental Medicine Pub Date : 2025-08-11 DOI: 10.1007/s10238-025-01827-4
Chaoyu Wang, Yan Wu, Shuping Li, Haiyan Min, Jun Liu, Yunhong Huang, Guo Wei, Wei Zhang, Min Wang, Xiaoqiong Tang, Qing Xiao, Zailin Yang, Xiaomei Zhang, Hui Zhou, Yaokai Chen, Yao Liu
{"title":"A national, multicenter, retrospective study of human immunodeficiency virus infection-associated lymphoma in China.","authors":"Chaoyu Wang, Yan Wu, Shuping Li, Haiyan Min, Jun Liu, Yunhong Huang, Guo Wei, Wei Zhang, Min Wang, Xiaoqiong Tang, Qing Xiao, Zailin Yang, Xiaomei Zhang, Hui Zhou, Yaokai Chen, Yao Liu","doi":"10.1007/s10238-025-01827-4","DOIUrl":"10.1007/s10238-025-01827-4","url":null,"abstract":"<p><p>Since the widespread use of combination antiretroviral therapy, the incidence of opportunistic infections has decreased in HIV infection populations. However, HIV-associated lymphoma become the most common causes of cancer death. Little is known about the epidemiology, survival and treatment of HIV-associated lymphoma patients in China as these are less common than HIV-negative lymphoma. We performed a multi-center retrospectively study to analyze the epidemiology, clinical characteristics and outcomes of HIV-associated lymphoma in China. Totally 407 newly diagnosed HIV-associated lymphoma patients at eleven medical centers from July 2008 to October 2021, were analyzed, as the largest cohort reported in China to date. In the entire cohort, including 373 (91.6%) B-cell lymphoma, 19 (4.7%) HL patients, and 11 (2.7%) T-cell lymphoma. Among B-cell lymphoma, DLBCL was the most common (n = 273, 73.2%), followed by BL (n = 47, 12,6%). The median age was 47 years (range, 18-90) at lymphoma diagnosis, and 332 patients were male (81.6%), 254 patients (62.4%) were diagnosed with advanced stage (III/IV). In the entire cohort, 57 (14.0%) patients did not receive anti-lymphoma treatment, 350 patients (86.0%) underwent chemotherapy as part of their first-line treatment. More than half of them (241/350, 68.9%) had underwent 4 cycles or more of chemotherapy. The median follow-up of our cohort was 65 (36-186) months. The estimated 5-year OS rates in the HL and NHL cohort were 83.6% and 50.9%, respectively. The 5-year OS rates demonstrated an inverse correlation with ART duration prior to lymphoma diagnosis: 65.4% for patients not receiving ART before lymphoma diagnosis, 54.2% for those on ART for less than 12 months, and 42.8% for those on ART for ≥ 12 months (p = 0.014). This study depicts a broad picture of HIV-associated lymphoma, treatment options and survival information in China. These data suggested that HIV-associated lymphoma patients presented with aggressive clinical characteristics and rituximab, enhanced chemotherapy administration and shorter ART duration before lymphoma diagnosis was significantly associated with improved outcomes.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"285"},"PeriodicalIF":3.5,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12339615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144815864","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}
引用次数: 0
Polymyositis-like hypothyroid myopathy: diagnostic challenges and therapeutic outcomes in a case series. 多肌炎样甲状腺功能减退肌病:诊断挑战和治疗结果在一个病例系列。
IF 3.5 4区 医学
Clinical and Experimental Medicine Pub Date : 2025-08-11 DOI: 10.1007/s10238-025-01828-3
Fuyong Qiang, Qian He, Li Wang, Jun Sheng
{"title":"Polymyositis-like hypothyroid myopathy: diagnostic challenges and therapeutic outcomes in a case series.","authors":"Fuyong Qiang, Qian He, Li Wang, Jun Sheng","doi":"10.1007/s10238-025-01828-3","DOIUrl":"10.1007/s10238-025-01828-3","url":null,"abstract":"<p><p>Hypothyroid myopathy, affecting 30-80% of hypothyroid patients, often mimics polymyositis, posing diagnostic challenges. This retrospective case series analyzed 10 patients (70% female, mean age 46.1 ± 10.3 years) with polymyositis-like hypothyroid myopathy. All presented with proximal muscle weakness, myalgia, and/or arthralgia, accompanied by elevated muscle enzymes (CK, CK-MB, LDH), liver dysfunction (70%), hyperlipidemia (70%), and serous effusions (pericardial effusion: 70%). Notably, all patients tested negative for myositis antibodies but exhibited thyroid dysfunction (↓fT3/fT4, ↑TSH) and positive thyroglobulin antibodies (100%). Muscle biopsies revealed degeneration and atrophy without necrosis or inflammation. After 3 months of thyroxine replacement therapy (100-150 µg/day), symptoms significantly improved (P < 0.05), with reductions in ALT, AST, CHOL, CK, CK-MB, and LDH (all P < 0.01), and normalization of fT3/fT4 levels. Muscle enzyme levels correlated negatively with fT3/fT4 (r<sub>s</sub> =  - 0.76 to - 0.78, P < 0.05) and positively with TSH (r<sub>s</sub> = 0.70 to 0.72, P < 0.05). This study highlights the multisystem manifestations of hypothyroid myopathy (metabolic, hepatic, serous) and underscores the importance of thyroid screening in unexplained myopathy, even in the absence of classic hypothyroidism symptoms. Early hormone replacement therapy yields an excellent prognosis.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"286"},"PeriodicalIF":3.5,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12339587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144815867","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}
引用次数: 0
Identification of circulating immune response-related biomarkers in patients with ANCA-associated glomerulonephritis. anca相关性肾小球肾炎患者循环免疫反应相关生物标志物的鉴定
IF 3.5 4区 医学
Clinical and Experimental Medicine Pub Date : 2025-08-11 DOI: 10.1007/s10238-025-01841-6
Yujie He, Wenjun Cao, Weiwei Hao, Yifan Ma, Ying Li, Yuting Ma, Lin Lin, Wei Li
{"title":"Identification of circulating immune response-related biomarkers in patients with ANCA-associated glomerulonephritis.","authors":"Yujie He, Wenjun Cao, Weiwei Hao, Yifan Ma, Ying Li, Yuting Ma, Lin Lin, Wei Li","doi":"10.1007/s10238-025-01841-6","DOIUrl":"10.1007/s10238-025-01841-6","url":null,"abstract":"<p><p>This study aimed to investigate the profiles of immune response-related proteins in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (ANCA-GN) and identify potential biomarkers for this disease. Plasma was collected from patients with ANCA-GN and healthy controls (HCs). Immune-related proteins were measured using the Immune Response Panel 80-Plex. Differentially expressed proteins (DEPs) were used to differentiate patients with ANCA-GN from HCs via ROC analysis. The prediction performance of the potential biomarkers was assessed using the area under the curve (AUC). Detection results for the immune response-related proteins showed 54 DEPs between ANCA-GN patients and HCs. KEGG enrichment analysis of these 54 DEPs revealed that were mainly enriched in chemokine signaling pathway, IL17 signaling pathway, and JAK-STAT signaling pathway. Among the top 14 core proteins in the protein-protein interaction network, 8 were closely related to renal function, namely IL1A, IFNG, CXCL9, CXCL10, CXCL11, IL4, IL5, and CCL11. The performance of the potential biomarkers for discriminate ANCA-GN was as follows: CCL11, AUC: 0.998; IL4, AUC: 0.950; CXCL9, AUC: 0.917; CXCL10, AUC: 0.887; CXCL11, AUC: 0.807; and IFNG, AUC: 0.821 (all P < 0.001). Distinct immune-related protein profiles were identified in ANCA-GN, and present study revealed that CCL11, IL4, CXCL9, CXCL10, CXCL11, and IFNG could act as potential biomarkers for this disease. In addition, these circulating immune mediators are closely associated with renal function.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"289"},"PeriodicalIF":3.5,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12339652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144815866","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}
引用次数: 0
Telitacicept plus low-dose mycophenolate mofetil in the treatment of IgA nephropathy: a retrospective study. 替利他塞普联合低剂量霉酚酸酯治疗IgA肾病的回顾性研究。
IF 3.5 4区 医学
Clinical and Experimental Medicine Pub Date : 2025-08-11 DOI: 10.1007/s10238-025-01829-2
Huapan Shu, Yujuan Wang, Xiaoqing Li, Lu Zhang, Zhongping Wei, Yuan Song, Ju Chen, Hui Cheng, Cheng Chen, Wei Liang, Huiming Wang, Xinghua Chen
{"title":"Telitacicept plus low-dose mycophenolate mofetil in the treatment of IgA nephropathy: a retrospective study.","authors":"Huapan Shu, Yujuan Wang, Xiaoqing Li, Lu Zhang, Zhongping Wei, Yuan Song, Ju Chen, Hui Cheng, Cheng Chen, Wei Liang, Huiming Wang, Xinghua Chen","doi":"10.1007/s10238-025-01829-2","DOIUrl":"10.1007/s10238-025-01829-2","url":null,"abstract":"<p><p>Presently, no specific therapies have been recognized for immunoglobulin A nephropathy (IgAN). Mycophenolate mofetil (MMF) has been verified effective for Chinese patients with IgAN. Telitacicept is a full-human TACI-FC fusion preventing B cells maturation and activation, and it has been proven to be beneficial for IgAN in a phase II clinical trial. This study was designed to observe the efficacy and safety of telitacicept plus low-dose MMF for IgAN treatment. This retrospective cohort study included 24 patients with IgAN, and patients were treated with telitacicept plus MMF. The primary outcome was settled as the changing in proteinuria and estimated glomerular filtration rate (eGFR). The subordinate outcome was set as the changing in hematuria. The mean follow-up time was 23 months. The median baseline proteinuria was 2.5 (1.74, 6.58) g/d, and eGFR was 94.97 (56.8, 120.67) mL/min/1.73 m<sup>2</sup>. There were noteworthy reductions in proteinuria at 3, 6, 9, 12, 15, 18, 21 and 24 months when compared to the baseline levels [1.45 (0.78, 1.8) g/d [p = 0.0122], 0.505 (0.26, 0.99) g/d [p < 0.0001], 0.48 (0.28, 0.76) g/d [p < 0.0001], 0.3 (0.17, 0.85) g/d [p < 0.0001], 0.23 (0.18, 0.575) g/d [p < 0.0001], 0.18 (0.12, 0.325) g/d [p < 0.0001], 0.14 (0.105, 0.22) g/d [p < 0.0001] and 0.14 (0.103, 0.278) g/d [p < 0.0001]]. All patients maintained stable eGFR during follow-up times. Besides, telitacicept plus MMF remarkably alleviated the hematuria. Telitacicept plus MMF treatment led to not only remarkable clinically significant reduction in proteinuria and hematuria, but also stable serum creatinine value of patients with IgAN without adverse side effects.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"287"},"PeriodicalIF":3.5,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12339650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144815868","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}
引用次数: 0
Advances in mechanistic investigation and treatment of steroid-refractory ICI-induced liver injury. 类固醇难治性ici肝损伤的机制研究及治疗进展。
IF 3.5 4区 医学
Clinical and Experimental Medicine Pub Date : 2025-08-11 DOI: 10.1007/s10238-025-01721-z
Haorui Hu, Xinyi Shen, Jiajia Chen
{"title":"Advances in mechanistic investigation and treatment of steroid-refractory ICI-induced liver injury.","authors":"Haorui Hu, Xinyi Shen, Jiajia Chen","doi":"10.1007/s10238-025-01721-z","DOIUrl":"10.1007/s10238-025-01721-z","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs) have revolutionized cancer immunotherapy, significantly improving patient survival. However, their use is frequently associated with immune-related adverse events, including immune checkpoint inhibitor-induced liver injury (ICI-DILI), which poses substantial clinical challenges. While corticosteroid therapy remains the primary treatment for ICI-DILI, many patients with steroid-refractory cases, especially those involving non-hepatocellular injury, exhibit resistance to standard therapies. Emerging evidence suggests that factors such as MDR1 expression, PD-L1 (Programmed cell death ligand (1)) and PD-L2 (Programmed cell death ligand (2)) expression levels, and liver injury patterns contribute to steroid resistance, highlighting the need for alternative treatment strategies. Recent advancements in therapeutic research have identified promising second-line treatments, including immunosuppressants (tacrolimus, cyclosporine A, mycophenolate mofetil, and azathioprine), monoclonal antibodies (infliximab and tocilizumab), anti-thymocyte globulin, intravenous immunoglobulin, ursodeoxycholic acid for cholestatic cases, and blood purification techniques. These innovations offer new possibilities for managing steroid-refractory ICI-DILI. This review also explores critical gaps in the field, including the lack of reliable diagnostic criteria and biomarkers for hormone-refractory ICI-DILI. Furthermore, we discuss the development of novel therapies informed by evolving insights into the condition's pathogenesis and the feasibility of reintroducing ICIs after ICI-DILI resolution. These advancements mark significant progress in optimizing patient outcomes and advancing the mechanistic understanding of ICI-DILI.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"288"},"PeriodicalIF":3.5,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12339640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144815865","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}
引用次数: 0
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