European Journal of Medical Research最新文献

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Transcriptional activation of MACF1 by NR2F1 drives WNT-mediated focal adhesion and metastasis in lung adenocarcinoma. NR2F1转录激活MACF1驱动wnt介导的肺腺癌局灶性粘附和转移。
IF 3.4 3区 医学
European Journal of Medical Research Pub Date : 2025-10-16 DOI: 10.1186/s40001-025-03332-6
Yi Zhou, Jing Wang, Yangcheng Sun, Qiangyan Zhang, Xiangyu Su
{"title":"Transcriptional activation of MACF1 by NR2F1 drives WNT-mediated focal adhesion and metastasis in lung adenocarcinoma.","authors":"Yi Zhou, Jing Wang, Yangcheng Sun, Qiangyan Zhang, Xiangyu Su","doi":"10.1186/s40001-025-03332-6","DOIUrl":"10.1186/s40001-025-03332-6","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the regulatory role of MACF1 and its upstream transcriptional control in focal adhesion remodeling and tumor progression in lung adenocarcinoma (LUAD).</p><p><strong>Methods: </strong>We employed in vitro loss- and gain-of-function assays using shRNA-mediated knockdown and ectopic overexpression of MACF1 and NR2F1 in LUAD cell lines (H1299 and Calu-3). Cell proliferation, adhesion, and migration were assessed by CCK-8, EdU, crystal violet, and Transwell assays. In vivo tumor growth and metastasis were evaluated using subcutaneous and tail vein xenograft models in nude mice. RNA-seq and GSEA were performed to identify MACF1-regulated pathways, followed by nuclear-cytoplasmic fractionation, dual-luciferase reporter assays, and immunofluorescence to assess WNT/β-catenin activity. ChIP-qPCR and ChIP-seq data from ENCODE were used to validate NR2F1 binding to the MACF1 promoter.</p><p><strong>Results: </strong>MACF1 knockdown significantly suppressed LUAD cell proliferation, DNA replication, adhesion, and migration, and reduced tumor burden and lung metastases in vivo. Mechanistically, MACF1 activated WNT/β-catenin signaling by promoting CTNNB1 nuclear translocation, which upregulated focal adhesion genes (Paxillin, FAK, ITGB1). CTNNB1 agonist TWS119 restored focal adhesion in MACF1-deficient cells. Bioinformatic prediction and ChIP validation identified NR2F1 as a transcription factor directly targeting the MACF1 promoter. NR2F1 deficiency reduced MACF1 expression and phenocopied its functional loss, while MACF1 overexpression rescued the impaired phenotype.</p><p><strong>Conclusion: </strong>Our study uncovers a previously unrecognized NR2F1-MACF1-WNT axis that drives focal adhesion formation and LUAD progression. Targeting this regulatory circuit may offer new avenues for anti-metastatic therapy in lung adenocarcinoma.</p><p><strong>Highlights: </strong>1. NR2F1 is identified as a direct upstream transcription factor that activates MACF1 expression in LUAD. 2. MACF1 promotes LUAD cell proliferation, adhesion, and migration by enhancing focal adhesion assembly. 3. MACF1 activates the WNT/CTNNB1 signaling cascade, facilitating CTNNB1 nuclear translocation and downstream target expression. 4. Loss of MACF1 impairs focal adhesion formation and metastatic potential both in vitro and in xenograft and tail vein models. 5. The NR2F1-MACF1-WNT axis represents a novel regulatory circuit driving LUAD metastasis and offers potential therapeutic targets.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"988"},"PeriodicalIF":3.4,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12533429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 validation of a dynamic nomogram for predicting in-hospital mortality in acute massive cerebral infarction: a retrospective study in a Chinese population. 预测急性大面积脑梗死住院死亡率的动态图的建立和验证:一项中国人群的回顾性研究。
IF 3.4 3区 医学
European Journal of Medical Research Pub Date : 2025-10-16 DOI: 10.1186/s40001-025-03300-0
Xuhui Liu, Xujie Wang, Rongfei Xie, Zhaohui Liu, Shasha Liang, Jinyin Bai, Chunjian Ma
{"title":"Development and validation of a dynamic nomogram for predicting in-hospital mortality in acute massive cerebral infarction: a retrospective study in a Chinese population.","authors":"Xuhui Liu, Xujie Wang, Rongfei Xie, Zhaohui Liu, Shasha Liang, Jinyin Bai, Chunjian Ma","doi":"10.1186/s40001-025-03300-0","DOIUrl":"10.1186/s40001-025-03300-0","url":null,"abstract":"<p><strong>Background: </strong>Massive cerebral infarction (MCI) is a severe form of ischemic stroke that can result in adverse outcomes, including death. This study aimed to identify the independent risk factors associated with MCI mortality by developing a multivariate model using stepwise logistic regression analysis.</p><p><strong>Methods: </strong>This retrospective study included 159 hospitalized patients between January 15, 2022, and October 20, 2023. The diagnosis of MCI was based on clinical symptoms, the National Institutes of Health Stroke Scale (NIHSS), the Glasgow Coma Scale (GCS), and brain MRI. Potential mortality-related predictors were identified by analyzing patient histories, coagulation profiles, renal function, and serum biochemical indicators such as fasting blood glucose (FBG), homocysteine (HCY), and hemoglobin (Hb).</p><p><strong>Results: </strong>Among the 159 patients, optimized multivariate logistic regression analysis revealed that smoking (OR = 10.48, 95% CI 2.85-42.80), FBG (OR = 1.97, 95% CI 1.45-2.82), HCY (OR = 8.62, 95% CI 1.29-76.21), Hb (OR = 0.96, 95% CI 0.94-0.99), and GCS score (OR = 0.67, 95% CI 0.52-0.83) were significantly associated with in-hospital mortality (all P < 0.05). The model showed good discrimination (AUC = 0.943, 95% CI 0.903-0.982), with a marginal R-squared (R<sup>2</sup>M) of 0.660. Calibration and decision curve analyses suggested good predictive performance and potential clinical utility of the nomogram.</p><p><strong>Conclusion: </strong>Smoking, elevated FBG and HCY, low Hb, and lower GCS scores were identified as independent predictors of mortality in MCI patients. Managing these factors may help reduce the risk of death.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"981"},"PeriodicalIF":3.4,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12529824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145299315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Decoding the link between ischemic stroke and myocardial infarction: a pathophysiological and clinical perspective. 解码缺血性中风和心肌梗死之间的联系:病理生理和临床的观点。
IF 3.4 3区 医学
European Journal of Medical Research Pub Date : 2025-10-16 DOI: 10.1186/s40001-025-03221-y
Ling Chen, Senrong Luo, Mingzhu Feng, Ayush Chandra, José Fidel Baizabal-Carvallo, Mohammad Mofatteh, Jiale Wu, Yuankang He, Zhikai Chen, Xiaoru Zeng, Junrong Tu, Xuejun Wang, Xuxing Liao
{"title":"Decoding the link between ischemic stroke and myocardial infarction: a pathophysiological and clinical perspective.","authors":"Ling Chen, Senrong Luo, Mingzhu Feng, Ayush Chandra, José Fidel Baizabal-Carvallo, Mohammad Mofatteh, Jiale Wu, Yuankang He, Zhikai Chen, Xiaoru Zeng, Junrong Tu, Xuejun Wang, Xuxing Liao","doi":"10.1186/s40001-025-03221-y","DOIUrl":"10.1186/s40001-025-03221-y","url":null,"abstract":"<p><p>Ischemic stroke and myocardial infarction (MI) are among the leading causes of morbidity and mortality globally. Recent research has increasingly highlighted the significant interrelation between these two vascular events, emphasizing shared pathophysiological mechanisms, overlapping risk factors, and complex clinical outcomes. This review explores the multifaceted relationship between ischemic stroke and MI, focusing on their common underlying mechanisms, including atherosclerosis, thromboembolism, inflammation, and endothelial dysfunction. Both conditions often co-occur due to their shared risk factors, such as hypertension, diabetes, and smoking, leading to compounded health risks for affected individuals. This review aims to synthesize current evidence on the epidemiological, pathophysiological, and clinical interrelationships between ischemic stroke and myocardial infarction, highlighting practical clinical implications and areas for future research. Although ischemic stroke and myocardial infarction primarily affect distinct organ systems, atypical presentations and shared systemic effects can occasionally complicate diagnosis. Cardiac complications are common in acute ischemic stroke, while stroke-like symptoms may arise in patients with acute MI, especially when silent infarctions occur. This diagnostic challenge underscores the need for advanced neuroimaging and cardiac imaging modalities, alongside biomarkers like D-dimer, BNP, and troponins, to enhance early detection and guide therapeutic decisions. Therapeutic strategies for patients with both conditions must be comprehensive, combining acute management with long-term secondary prevention. While antiplatelet therapy, thrombolysis, and anticoagulation are essential in the acute phase, long-term management involves a focus on controlling cardiovascular risk factors, such as blood pressure and cholesterol, and promoting lifestyle modifications. The role of interdisciplinary care-particularly collaboration between cardiology and neurology-is essential for improving outcomes and minimizing complications. The intersection of ischemic stroke and MI presents significant clinical challenges but also opportunities for enhanced patient management. Integrated diagnostic approaches, personalized treatments, and further research into molecular mechanisms are vital for improving the prognosis of individuals affected by both conditions.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"984"},"PeriodicalIF":3.4,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12533319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Targeting SHP-1 to alleviate testicular inflammation and apoptosis in a Poly(I:C)-induced orchitis model. 在Poly(I:C)诱导的睾丸炎模型中,靶向SHP-1减轻睾丸炎症和细胞凋亡。
IF 3.4 3区 医学
European Journal of Medical Research Pub Date : 2025-10-16 DOI: 10.1186/s40001-025-03103-3
Shimin Wang, Jianing Tong, Bicheng Jin, Qiong Lei, Qingliang Zheng
{"title":"Targeting SHP-1 to alleviate testicular inflammation and apoptosis in a Poly(I:C)-induced orchitis model.","authors":"Shimin Wang, Jianing Tong, Bicheng Jin, Qiong Lei, Qingliang Zheng","doi":"10.1186/s40001-025-03103-3","DOIUrl":"10.1186/s40001-025-03103-3","url":null,"abstract":"<p><p>Orchitis, an inflammation of the testes primarily caused by viral infections such as mumps, presents a significant threat to male reproductive health. This study explores the role of Src homology 2 (SH2)-containing tyrosine phosphatase-1 (SHP-1), a known tumor suppressor, in mitigating inflammation and apoptosis in testicular cells within a model of viral-induced orchitis. To simulate the immune response associated with viral orchitis, we utilized Poly (I:C), a synthetic analog of double-stranded RNA, which mimics the molecular patterns of viral RNA. This model provides a relevant framework for investigating immune responses in the testes triggered by viral-like stimuli. Our research aimed to elucidate the impact of SHP-1 expression on the inflammatory and apoptotic pathways activated during testicular inflammation. We found that Poly (I:C) induced significant inflammation and apoptosis in Leydig and Sertoli cells, characterized by reduced SHP-1 expression and elevated phosphorylated-STAT3 levels. Enhancing SHP-1 expression attenuated these inflammatory and apoptotic responses, whereas reactivating STAT3 with colivelin reversed the suppression of cytokine production and cell death. Moreover, inhibiting SHP-1 with TPI-1 treatment post-Poly (I:C) administration significantly exacerbated testicular inflammation and apoptosis, underscoring SHP-1's critical protective role. These findings highlight the therapeutic potential of targeting SHP-1 and STAT3 pathways in treating orchitis, advancing our understanding of the pathophysiology of testicular inflammation and suggesting new strategies for managing this condition.Author details: Please check if the designated corresponding authors affiliation is correctly identify and amend if necessary. Please see the attached file containing the updated author information for our manuscript. Author names: Please confirm if all the authors names are presented accurately and in the correct sequence. Kindly check and confirm whether the names of all authors has been processed correctly and amend if necessary. Please see the attached file containing the updated author information for our manuscript.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"983"},"PeriodicalIF":3.4,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12533441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Prevalence, characteristics, and treatment outcomes of epilepsy in Nigeria: a systematic review and meta-analysis. 尼日利亚癫痫的患病率、特征和治疗结果:系统回顾和荟萃分析
IF 3.4 3区 医学
European Journal of Medical Research Pub Date : 2025-10-16 DOI: 10.1186/s40001-025-02980-y
Nicholas Aderinto, Bonaventure Ukoaka, Gbolahan Olatunji, Emmanuel Kokori, Samson Afolabi, Adetola Emmanuel Babalola, Ismaila Yusuf, Ikponmwosa Jude Ogieuhi, Abdulrahmon Moradeyo, Opabode Muntaqim Obasanjo, Adefusi Oluwakorede, Oluwatobi Omoworare, Yewande Abigail Adebayo
{"title":"Prevalence, characteristics, and treatment outcomes of epilepsy in Nigeria: a systematic review and meta-analysis.","authors":"Nicholas Aderinto, Bonaventure Ukoaka, Gbolahan Olatunji, Emmanuel Kokori, Samson Afolabi, Adetola Emmanuel Babalola, Ismaila Yusuf, Ikponmwosa Jude Ogieuhi, Abdulrahmon Moradeyo, Opabode Muntaqim Obasanjo, Adefusi Oluwakorede, Oluwatobi Omoworare, Yewande Abigail Adebayo","doi":"10.1186/s40001-025-02980-y","DOIUrl":"10.1186/s40001-025-02980-y","url":null,"abstract":"<p><strong>Background: </strong>Epilepsy poses a significant health burden globally. In Nigeria, limited access to healthcare and potential regional variations in risk factors necessitate an understanding of epilepsy's characteristics and treatment. This study addresses this gap by conducting a systematic review and meta-analysis to investigate the prevalence, demographic variations, seizure types, and treatment modalities of epilepsy in Nigeria.</p><p><strong>Methods: </strong>A systematic review was conducted following PRISMA guidelines (CRD42024549637). We searched PubMed, Google Scholar, and other databases (6 total) from inception to February 2024 using a combination of MeSH terms and keywords related to epilepsy and Nigeria. Studies included observational studies, clinical trials, and those reporting on the prevalence, characteristics, and management of epilepsy in Nigeria. We excluded studies outside Nigeria, lacking relevant data, or non-research materials. Two reviewers screened titles/abstracts and full texts for eligibility. Data extraction included demographics, sample size, location, seizure type, and treatment outcomes. The JBI tool assessed study quality. We did systematic synthesis and meta-analysis for prevalence.</p><p><strong>Results: </strong>The prevalence of epilepsy ranged from 0.45 to 36.09%. The overall pooled prevalence of epilepsy is 14.21% (95% CI 1.56-36.16) among all age group patients. Children presented with the highest prevalence (36.09%), followed by adults (11.85%) and in combine adult and children studies (3.16%). The South-South zone had the highest prevalence (21.73%), while the North-Central zone had the lowest (0.47%). Generalized tonic-clonic seizures were the most common type reported (76.9-83.13%). Carbamazepine was a frequent first-line treatment, with some studies indicating good results, particularly in children. Monotherapy was generally preferred.</p><p><strong>Conclusion: </strong>Epilepsy prevalence in Nigeria varies considerably. Children and the South-South zone appear to be more affected. Carbamazepine is a common first-line treatment. Further research is required to explore underlying causes, optimal treatment strategies, and adherence challenges.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"986"},"PeriodicalIF":3.4,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12533339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Assessing the association between multiple indicators of inflammation and sleep disorders in young and middle-aged women: insights from traditional and machine learning approaches. 评估年轻和中年女性炎症和睡眠障碍的多个指标之间的关联:来自传统和机器学习方法的见解。
IF 3.4 3区 医学
European Journal of Medical Research Pub Date : 2025-10-15 DOI: 10.1186/s40001-025-03203-0
Yi Tang, Kangrui Zhang, Xin Tang, Yueyu Zhang, Jiaxuan Li, Xinhui Jia, Xun He, Xinyi Chen, Jie Hu, Zhinan Ye, Juncang Wu
{"title":"Assessing the association between multiple indicators of inflammation and sleep disorders in young and middle-aged women: insights from traditional and machine learning approaches.","authors":"Yi Tang, Kangrui Zhang, Xin Tang, Yueyu Zhang, Jiaxuan Li, Xinhui Jia, Xun He, Xinyi Chen, Jie Hu, Zhinan Ye, Juncang Wu","doi":"10.1186/s40001-025-03203-0","DOIUrl":"10.1186/s40001-025-03203-0","url":null,"abstract":"<p><strong>Background: </strong>Interactions between inflammation and sleep disorders are increasingly recognized; however, limited research comprehensively evaluates the association between multiple inflammatory indicators and sleep disorders.</p><p><strong>Methods: </strong>This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES, 2015-2020) involving 2,342 participants. Machine learning algorithms were employed to identify inflammatory indicators with potential predictive value for sleep disorders, followed by Shapley value analysis to quantify their contributions. Weighted logistic regression and restricted cubic spline models were applied to examine associations between key inflammatory markers and sleep disorders. Mediation analysis was conducted to assess the role of depression in these relationships. Receiver operating characteristic (ROC) curves were generated to compare the predictive performance of individual inflammatory markers. Sensitivity analyses using E-values were performed to evaluate the robustness of findings against unmeasured confounding.</p><p><strong>Results: </strong>Alpha-1-acid glycoprotein, C-reactive protein, and Naples Prognosis Score all showed significant positive correlations with sleep disorders. Among these, AGP and CRP contributed most significantly to the model (Shap value≈0.23). Furthermore, mediation analysis indicated that depression mediated 15.1% of the total effect of AGP on sleep disorders.</p><p><strong>Conclusions: </strong>The study confirms a significant positive association between serum AGP levels and sleep disorders. Among the inflammatory markers evaluated, AGP exhibited the strongest correlation, underscoring its potential clinical relevance in the pathophysiology of sleep disturbances.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"972"},"PeriodicalIF":3.4,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12522555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Cardiovascular disease mortality risk among patients with metastatic melanoma before and after the approval of immunotherapy in the United States: a Surveillance, Epidemiology, and End Results database-based study. 美国免疫疗法批准前后转移性黑色素瘤患者心血管疾病死亡风险:一项基于监测、流行病学和最终结果数据库的研究
IF 3.4 3区 医学
European Journal of Medical Research Pub Date : 2025-10-15 DOI: 10.1186/s40001-025-03255-2
Xiaoqin Luo, Jiaying Niu, Yufeng Zhang, Yanni Jia, Qiannan Wang, Yuanyuan Li, Yonghuan Wang, Jinglian Li, Zhenhua Li, Rui Yan, Sijin Li
{"title":"Cardiovascular disease mortality risk among patients with metastatic melanoma before and after the approval of immunotherapy in the United States: a Surveillance, Epidemiology, and End Results database-based study.","authors":"Xiaoqin Luo, Jiaying Niu, Yufeng Zhang, Yanni Jia, Qiannan Wang, Yuanyuan Li, Yonghuan Wang, Jinglian Li, Zhenhua Li, Rui Yan, Sijin Li","doi":"10.1186/s40001-025-03255-2","DOIUrl":"10.1186/s40001-025-03255-2","url":null,"abstract":"<p><strong>Background: </strong>To date, the population-based cardiovascular mortality (CVM) of metastatic melanoma has not been studied in the era of immune checkpoint inhibitors (ICIs). This study aims to assess the risk of CVM in patients with metastatic melanoma in the pre-ICI (2000-2010) and post-ICI (2011-2020) eras.</p><p><strong>Methods: </strong>This study using the Surveillance, Epidemiology, and End Results database from 2000 to 2020 of patients with metastatic melanoma. Standardized mortality ratios (SMRs) and absolute excess risks were calculated for CVM before and after the introduction of ICIs. To evaluate the cumulative mortality (CM) rate for all causes of death, cumulative hazard curves were constructed. Competing risk models were established to determine the independent predictors for CVM.</p><p><strong>Results: </strong>This study included 8857 patients, 3803 in the pre-ICI era and 5054 in the post-ICI era. A total of 281 deaths were attributed to cardiovascular diseases. The overall SMRs of CVM were 27% higher (SMR = 1.27, 95% CI 1.06-1.50) in the pre-ICI era and 56% higher (SMR = 1.56, 95% CI 1.31-1.83) in the post-ICI era than the general population, reaching 2.17 during the early stage of latency (0-5 months). Additionally, independent risk factors for CVM included age, primary site, and brain metastases in the post-ICI era.</p><p><strong>Conclusions: </strong>Metastatic melanoma patients exhibited an elevated CVM risk after the approval of ICIs, peaking in early latency period and older population. Timely monitoring and effective interventions for cardiovascular diseases may be warranted in patients with metastatic melanoma, especially in the immunotherapy era.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"977"},"PeriodicalIF":3.4,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12522296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145299335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Effects of different reperfusion durations on neuronal mitochondrial ultrastructure following cerebral ischemia in diabetic rats: a transmission electron microscopy study. 不同再灌注时间对糖尿病大鼠脑缺血后神经元线粒体超微结构影响的透射电镜研究。
IF 3.4 3区 医学
European Journal of Medical Research Pub Date : 2025-10-15 DOI: 10.1186/s40001-025-03273-0
Dan Wang, Gui-Sheng Chen
{"title":"Effects of different reperfusion durations on neuronal mitochondrial ultrastructure following cerebral ischemia in diabetic rats: a transmission electron microscopy study.","authors":"Dan Wang, Gui-Sheng Chen","doi":"10.1186/s40001-025-03273-0","DOIUrl":"10.1186/s40001-025-03273-0","url":null,"abstract":"<p><strong>Objective: </strong>This study employed transmission electron microscopy (TEM) to characterize the temporal dynamics of neuronal mitochondrial ultrastructural alterations following cerebral ischemia-reperfusion (I/R) in diabetic rats.</p><p><strong>Methods: </strong>Male Wistar rats were divided into four groups: hyperglycemic, normoglycemic, hyperglycemic cerebral ischemia, and normoglycemic cerebral ischemia. Diabetic rat models were established via streptozotocin (STZ) induction. Cerebral ischemia was induced by bilateral common carotid artery occlusion combined with hypotension for 10 min, followed by reperfusion for 5 h, 1 day, or 7 days. Neurological deficits were evaluated using the Longa scoring criteria, and mitochondrial damage in the cortical region was assessed by TEM. Transmission electron micrographs were analyzed using ImageJ software (National Institutes of Health, USA).</p><p><strong>Results: </strong>(1) Diabetic rats exhibited exacerbated neuronal and mitochondrial damage compared with normoglycemic controls after I/R, with the most severe injury observed at 5 h of reperfusion. (2) Quantitative analysis revealed significantly greater mitochondrial swelling and cristae disruption in the hyperglycemic I/R group at all time points (p < 0.01). (3) Although prolonged reperfusion time correlated with gradual recovery of mitochondrial integrity, this recovery was significantly delayed and incomplete in diabetic rats compared with normoglycemic controls.</p><p><strong>Conclusions: </strong>(1) A diabetic cerebral I/R injury model was successfully established using STZ combined with bilateral carotid artery occlusion and hypotension. (2) Diabetes markedly exacerbates and prolongs mitochondrial damage following cerebral I/R. Impaired recovery of mitochondrial ultrastructure represents a critical determinant of stroke prognosis in diabetic patients, providing a well-defined therapeutic target for subsequent fundamental research and intervention strategies.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"979"},"PeriodicalIF":3.4,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12522883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145299342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Associations of carotid flow velocity with cerebral perfusion and cerebral small vessel disease: a community-based prospective study. 颈动脉血流速度与脑灌注和脑血管疾病的关系:一项基于社区的前瞻性研究
IF 3.4 3区 医学
European Journal of Medical Research Pub Date : 2025-10-15 DOI: 10.1186/s40001-025-03238-3
Peipei Yang, Xiaoshuai Li, Yuqing Huang, Xinyu Zhao, Ying Hui, Shouling Wu, Zhenchang Wang, Xian-Quan Shi
{"title":"Associations of carotid flow velocity with cerebral perfusion and cerebral small vessel disease: a community-based prospective study.","authors":"Peipei Yang, Xiaoshuai Li, Yuqing Huang, Xinyu Zhao, Ying Hui, Shouling Wu, Zhenchang Wang, Xian-Quan Shi","doi":"10.1186/s40001-025-03238-3","DOIUrl":"10.1186/s40001-025-03238-3","url":null,"abstract":"<p><strong>Objectives: </strong>To explore the associations of carotid artery hemodynamic parameters with cerebral perfusion and cerebral small vessel disease (CSVD) in a healthy population.</p><p><strong>Methods: </strong>A total of 654 participants from the Kailuan community were included after those with incomplete data or carotid stenosis ≥ 50% were excluded. Carotid ultrasound was used to measure the peak carotid flow velocity (PSV), end-diastolic velocity (EDV), resistance index (RI), pulsatility index (PI) and carotid intima-media thickness (IMT) of the common carotid artery (CCA) and internal carotid artery (ICA). MRI was performed to assess cerebral perfusion and CSVD features, including white matter hyperintensities (WMH), lacunes (LA), cerebral microbleeds (CMB), and enlarged perivascular spaces (EPVS). Multivariate regression models were used to analyze the associations of carotid hemodynamics with cerebral perfusion and CSVD.</p><p><strong>Results: </strong>CCA-EDV was positively associated with whole-brain perfusion (β = 0.14, p = 0.017) and regional perfusion in gray matter (GM) (β = 0.16, p = 0.012), frontal (β = 0.15, p = 0.014), parietal (β = 0.19, p = 0.006), temporal (β = 0.14, p = 0.020), and hippocampus (β = 0.12, p = 0.034), but no significant associations were found between CCA-EDV and white matter (WM) perfusion. A higher CCA-EDV was associated with a lower risk of LA (OR = 0.93, p = 0.029). The CCA-PSV was negatively correlated with the total CSVD score (OR = 0.99, p = 0.047). No significant associations were detected between other carotid hemodynamic parameters and LA, CMB, EPVS, WMH, or total CSVD score.</p><p><strong>Conclusions: </strong>Carotid artery hemodynamic parameters, especially the CCA-EDV, are closely related to cerebral perfusion and the development of CSVD. Reductions in total and regional cerebral perfusion, along with an increased LA burden, were associated with decreased CCA-EDV.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"976"},"PeriodicalIF":3.4,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12522649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145299276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 role of SPRED1 mutation in melanoma. SPRED1突变在黑色素瘤中的作用。
IF 3.4 3区 医学
European Journal of Medical Research Pub Date : 2025-10-15 DOI: 10.1186/s40001-025-03267-y
Hui Hou, Jiao Li, Jianxiao Xing, Ruixia Hou
{"title":"The role of SPRED1 mutation in melanoma.","authors":"Hui Hou, Jiao Li, Jianxiao Xing, Ruixia Hou","doi":"10.1186/s40001-025-03267-y","DOIUrl":"10.1186/s40001-025-03267-y","url":null,"abstract":"<p><p>Melanoma is a highly malignant tumor, with its initiation and progression tightly linked to the aberrant activation of the MAPK signaling pathway. As a critical negative regulator of the MAPK pathway, SPRED1 frequently exhibits genomic alteration in melanoma, including gene deletions and mutations, which lead to its functional inactivation. Consequently, the loss of SPRED1-mediated inhibition on the MAPK pathway significantly drives tumorigenesis and progression, enhances invasive and metastatic capacities, and is closely associated with therapeutic resistance. This article systematically reviews the structure and biological functions of SPRED1, its mutation profiles across different melanoma subtypes, and its regulatory mechanisms on the MAPK pathway. Furthermore, it discusses the associations of SPRED1 alteration with tumor malignant progression, as well as resistance to targeted therapy and immunotherapy. This review aims to provide a comprehensive theoretical basis for the precise diagnosis, treatment, and fundamental research of melanoma.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"973"},"PeriodicalIF":3.4,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12522276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145299345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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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