European Journal of Medical Research最新文献

{"title":"Vitamin D and calcium supplementation in women undergoing pharmacological management for postmenopausal osteoporosis: a level I of evidence systematic review.","authors":"Filippo Migliorini, Nicola Maffulli, Giorgia Colarossi, Amelia Filippelli, Michael Memminger, Valeria Conti","doi":"10.1186/s40001-025-02412-x","DOIUrl":"10.1186/s40001-025-02412-x","url":null,"abstract":"<p><p>The present systematic review investigates whether different doses of vitamin D and calcium supplementation in women with postmenopausal osteoporosis undergoing antiresorptive therapy have an association with BMD (spine, hip, femur neck), serum markers of osteoporosis (bone-ALP, NTX, CTX), the rate of pathological vertebral and non-vertebral fractures, adverse events, and mortality. This systematic review was conducted according to the PRISMA 2020 guidelines. PubMed, Google Scholar, Embase, and Scopus databases were accessed in September 2024. All randomised clinical trials (RCTs) comparing two or more treatments for postmenopausal osteoporosis supplemented with vitamin D and/or calcium were accessed. Only studies that indicated daily vitamin D and/or calcium supplementation doses were accessed. Data from 37 RCTs (43,397 patients) were retrieved. Patients received a mean of 833.6 ± 224.0 mg and 92.8 ± 228.7 UI of calcium and vitamin D supplementation, respectively. The mean length of the follow-up was 25.8 ± 13.3 months. The mean age of the patients was 66.4 ± 5.6 years, and the mean BMI was 25.2 ± 1.6 kg/m². There was evidence of a statistically significant negative association between daily vitamin D supplementation and gastrointestinal adverse events (r = - 0.5; P = 0.02) and mortality (r = - 0.7; P = 0.03). No additional statistically significant associations were evidenced. In postmenopausal women who undergo antiresorptive treatment for osteoporosis, vitamin D was associated with a lower frequency of gastrointestinal adverse events and mortality. Calcium supplementation did not evidence an association with any of the endpoints of interest.Level of evidence Level I, systematic review of RCTs.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"170"},"PeriodicalIF":2.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633901","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}

{"title":"Identification of TAP2 as a novel immune target in human cancers: insights from integrated bioinformatics and experimental approaches.","authors":"Lufei Yang, Jiawei Gui, Yilei Sheng, Junzhe Liu, Chong Wang, Zhansheng Fang, Le Huang, Zewei Tu, Xingen Zhu, Kai Huang","doi":"10.1186/s40001-025-02360-6","DOIUrl":"10.1186/s40001-025-02360-6","url":null,"abstract":"<p><strong>Background: </strong>Transporter 2, ATP binding cassette (ABC) subfamily B member (TAP2), encodes a protein within the ABC transporter superfamily. TAP2 plays a role in the progression of cancers, such as cervical, breast, and lung cancers. However, the relationship between TAP2 and cancer prognosis, immune cell infiltration, tumor microenvironment, and immunotherapy remains unexplored. Therefore, this study aims to investigate the effect of TAP2 expression on its role in predicting tumor prognosis and immunotherapy efficacy.</p><p><strong>Methods: </strong>Bioinformatics analyses such as Gene Set Enrichment Analysis, single-cell, and Connectivity Map analyses were used to comprehensively assess TAP2-related genomic alterations, prognostic value, enrichment pathways, single-cell expression patterns, and potential targeting inhibitors. In addition, molecular docking techniques were used to simulate drug binding to TAP2. WB and RT-qPCR were used to detect differences in TAP2 expression in glioma cell lines. The U251MG cell line was established with TAP2 overexpression. The effects of elevated TAP2 expression on GBM cell function was evaluated using various assays, including the Transwell migration, scratch, and clonal formation assays.</p><p><strong>Results: </strong>TAP2 exhibited aberrantly expression in tumor tissues with genomic alterations. TAP2 significantly correlates with poor prognosis across various cancers. It was also involved in immune-related pathways, immune infiltration, and immune checkpoint regulation, thereby influencing the tumor microenvironment and immune response to cancer. TAP2 was identified as a potential predictor of immunotherapy response and screened for potential targeted inhibitors for future therapeutic interventions.</p><p><strong>Conclusions: </strong>Our findings suggest that TAP2 may serve as a promising prognostic marker and immune target in human cancers, warranting further investigation into its role in tumor immunity.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"163"},"PeriodicalIF":2.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614162","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}

{"title":"Prediction of peripheral lymph node metastasis (LNM) in thyroid cancer using delta radiomics derived from enhanced CT combined with multiple machine learning algorithms.","authors":"Wenzhi Wang, Feng Jin, Lina Song, Jinfang Yang, Yingjian Ye, Junjie Liu, Lei Xu, Peng An","doi":"10.1186/s40001-025-02438-1","DOIUrl":"10.1186/s40001-025-02438-1","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to develop a model for predicting peripheral lymph node metastasis (LNM) in thyroid cancer patients by combining enhanced CT radiomic features with machine learning algorithms. It increased the clinical utility and interpretability of the predictions through SHAP (SHapley Additive exPlanation) values and nomograms for model explanation and visualization.</p><p><strong>Methods: </strong>Clinical and enhanced CT image data from 375 patients with thyroid cancer confirmed by postoperative pathology at Xiangyang No. 1 People's Hospital were collected from January 2015 to July 2023. Among them, there were 88 patients in the LNM group and 287 patients in the non-LNM group. The delta radiomic features of the tumours were extracted. Various machine learning algorithms (such as SVM, GBM, RF, XGBoost, KNN, and LightGBM) were trained on the clinical and radiomic feature data sets and used to construct a reliable prediction model. During model training, cross-validation was used to evaluate model performance, and the optimal model was selected. In addition, SHAP values were used to interpret the prediction results of the optimal model, analyse the contribution of each feature to the prediction results, and further develop a nomogram to visually display the prediction results.</p><p><strong>Results: </strong>Univariate analysis confirmed that sex, Hashimoto's disease, tumour adjacency to the thyroid capsule, pathological subtype, Delta Radscore, and Radscore 1 are risk factors for peripheral lymph node metastasis in thyroid cancer patients. The machine learning model based on enhanced CT radiomics performed well in predicting peripheral lymph node metastasis in thyroid cancer patients. In the test set, the optimal model, SVM, achieved high AUC (0.879), sensitivity (0.849), and specificity (0.769) values. Through SHAP value analysis, the importance and contribution of tumour adjacency to the thyroid capsule, pathological subtype, Delta Radscore, and Radscore 1 in the prediction were clarified, providing a more detailed and intuitive basis for clinical decision-making. The nomogram illustrated the model prediction process, facilitating understanding and application by clinicians.</p><p><strong>Conclusions: </strong>This study successfully constructed a model for predicting peripheral lymph node metastasis in thyroid cancer patients on the basis of enhanced CT radiomics combined with machine learning and improved the interpretability and clinical utility of the model through SHAP values and nomograms. The model not only improves the accuracy of predictions but also provides a more scientific and intuitive basis for clinical decision-making, with potential clinical application value.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"164"},"PeriodicalIF":2.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614185","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}

{"title":"Advances in multi-omics studies of microvascular invasion in hepatocellular carcinoma.","authors":"Lili Wang, Han Xin Xu, Rui Wang, Fachang Zhang, Diandian Deng, Xiaoyang Zhu, Qi Tan, Heng Yang","doi":"10.1186/s40001-025-02421-w","DOIUrl":"10.1186/s40001-025-02421-w","url":null,"abstract":"<p><p>Microvascular invasion (MVI) represents a pivotal independent prognostic factor for the recurrence of hepatocellular carcinoma (HCC) after surgery. It contributes to early intervention for potentially recurrent HCC to enhance patient outcomes and increase survival rates. Traditionally, the diagnosis of MVI has relied on postoperative pathological analysis, and accurate preoperative detection methodologies are lacking. Recent research suggests that multi-omics strategies play a role in definitively diagnosing MVI before surgery and offering personalized selection for clinical decision-making in HCC management. This review meticulously examines a multi-omics approach for the preoperative prediction of MVI in HCC patients, aiming to innovate diagnostic paradigms to anticipate postsurgical recurrence, thereby facilitating earlier and more personalized therapeutic strategies.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"165"},"PeriodicalIF":2.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614148","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}

{"title":"Vagus nerve stimulation alleviates myocardial injury following hepatic ischemia-reperfusion in rats by inhibiting ferroptosis via the activation of the SLC7A11/GPX4 axis.","authors":"Po Zhang, Yuanjing Qin, Haiyan Wang, Jinping Wang","doi":"10.1186/s40001-025-02416-7","DOIUrl":"10.1186/s40001-025-02416-7","url":null,"abstract":"<p><strong>Background: </strong>Vagus nerve stimulation (VNS) exhibits protective effects against remote organ injury following ischemia-reperfusion (I/R). However, its effects on acute myocardial injury induced by hepatic I/R in rats, and the underlying mechanisms, remain unclear.</p><p><strong>Methods: </strong>Thirty male rats were randomly assigned to five groups: Sham, I/R, VNS, VNS + Erastin, and VNS + DMSO. A hepatic I/R injury model was established by occluding the arterial and portal veins of the left and middle lobes of the liver for 1 h followed by 6 h of reperfusion. VNS was performed throughout the hepatic I/R process. Erastin was administered intraperitoneally 60 min before hepatic ischemia. Blood samples were collected from the left common carotid artery post-reperfusion to measure liver injury markers (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) and the myocardial injury marker (cardiac troponin I [cTnI]). Left ventricular myocardial tissue was also collected for ultrastructural analysis via transmission electron microscopy, reactive oxygen species (ROS) detection using dihydroethidium staining, and measurements of Fe²⁺ levels, malondialdehyde (MDA) concentration, glutathione (GSH) levels, and superoxide dismutase (SOD) activity. Western blotting assessed the expression of ferroptosis-related proteins SLC7A11 and GPX4 in the myocardial tissue.</p><p><strong>Results: </strong>VNS significantly reduced serum levels of ALT, AST, and cTnI, while also mitigating mitochondrial damage in cardiomyocytes. Additionally, VNS decreased ROS levels, alleviated iron overload, and reduced lipid peroxidation in myocardial tissue. These protective effects were associated with the activation of the SLC7A11/GPX4 axis, as evidenced by increased expression of these proteins in the VNS group. However, the cardioprotective effects of VNS were negated by the ferroptosis activator erastin, indicating that ferroptosis is involved in VNS-mediated cardioprotection.</p><p><strong>Conclusion: </strong>VNS protects against myocardial injury from hepatic ischemia-reperfusion, likely by inhibiting oxidative stress and ferroptosis through activation of the SLC7A11/GPX4 axis.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"162"},"PeriodicalIF":2.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11900121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613509","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}

{"title":"SLC7A11, a disulfidptosis-related gene, correlates with multi-omics prognostic analysis in hepatocellular carcinoma.","authors":"Shizhe Li, Xiaotong Wang, Junbo Xiao, Jun Yi","doi":"10.1186/s40001-025-02411-y","DOIUrl":"10.1186/s40001-025-02411-y","url":null,"abstract":"<p><strong>Background: </strong>This study sought to establish a risk score signature based on disulfidptosis-related genes (DRGs) to predict the prognosis of hepatocellular carcinoma (HCC) patients.</p><p><strong>Methods: </strong>The expression data of DRGs from the Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) was analyzed to develop and validate a DRG prognostic signature (DRGPS). In vitro, experiments were conducted to explore DRG expressions and roles in HCC tissues and cell lines. HCC tissue microarrays were employed to analyze SLC7A11 expression and its association with clinicopathological characteristics.</p><p><strong>Results: </strong>The DRGPS consisted of 5 DRGs (SLC7A11, MATN3, CLEC3B, CCNJL, and PON1). The survival rate of HCC patients in high-risk group was significantly lower than that in low-risk group. The DRGPS was also associated with the modulation of tumor microenvironment (TME), tumor mutation burden (TMB), stemness and chemosensitivity. Furthermore, pan-cancer analysis suggested that the DRGPS risk score was associated with immune infiltration and stemness in multiple cancers. Moreover, our DRGPS had potential for predicting treatment efficacy in HCC patients. Finally, we confirmed that downregulation of SLC7A11, a DRG, inhibited the proliferation and migration of HCC cells, while its high expression correlated with advanced TNM clinical stage and larger tumor size.</p><p><strong>Conclusions: </strong>This study systematically describes a novel DRGPS constructed for predicting HCC prognosis, providing a new approach to risk stratification and treatment options. It also investigates the expression and function of SLC7A11, contributing to further exploration of the molecular mechanism underlying disulfidptosis in HCC, as well as its prognostic and therapeutic implications.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"161"},"PeriodicalIF":2.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11900568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604549","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}

{"title":"A comparative analysis of transhepatic cardia-gastric fundus puncture vs. gastric body puncture for insufflation for CT-guided percutaneous gastrostomy.","authors":"Qi Xiao-Mei, Hu Chang-Ming, Liu Li, Liang Qing-Hua, Xiong Jun-Ru, Li Liang-Shan, Deng Liang-Yu, Tang Guang-Ying, Huang Xue-Quan, He Chuang","doi":"10.1186/s40001-025-02426-5","DOIUrl":"10.1186/s40001-025-02426-5","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the safety and efficacy of transhepatic cardia-gastric fundus puncture (TCFP) for insufflation for CT-guided percutaneous gastrostomy (CPG).</p><p><strong>Methods: </strong>The clinical data of 38 patients who underwent TCFP for insufflation and 161 patients who underwent percutaneous gastric body for insufflation at a single center were retrospectively analyzed. The operative time, success rate, complication rate, overall procedure time, and incidence of complications within 3 months were collected.</p><p><strong>Results: </strong>The success rate of insufflation was 100%, and no serious complications occurred during percutaneous gastric insufflation. The average time for insufflation via TCFP was 9.60 ± 6.62 min, and that via gastric body puncture was 8.71 ± 71.8 min, with no significant difference between the two (p = 0.485). The overall duration of gastrostomy in the TCFP group was 32.16 ± 10.27 min and 33.94 ± 13.82 min in the gastric body group, with no significant difference (p = 0.456). The incidence of submucosal air spread was 0% in the TCFP group and 9.9% in the gastric body group, with significant difference (p = 0.045). The complication rates following insufflation via TCFP and via gastric body puncture were 18.4% and 21.7%, respectively, with no significant difference between the two groups (p = 0.652). The perioperative pain score was 2 after insufflation via TCFP and via gastric body puncture, with no significant difference (p = 0.119). The overall mortality rate was 0 in the first postoperative month, with a 3-month mortality rate of 5% (10/199). The surviving patients showed a significant increase in weight from 51.81 ± 8.52 kg to 52.52 ± 9.39 kg at 3 months postoperatively (p = 0.009).</p><p><strong>Conclusions: </strong>TCFP for insufflation is safe and effective, with a 100% success rate and no increased risk of complications. The choice of procedure should be based on the patient's specific condition and the physician's experience.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"160"},"PeriodicalIF":2.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596481","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}

{"title":"Effect of oral ligustrazine phosphate with cerebroside carnosine on neurological function and serum inflammatory factors among patients with ischemic cerebrovascular disease: a quasi-experimental study.","authors":"Qiong Zhao, Zhongyang Liu","doi":"10.1186/s40001-025-02414-9","DOIUrl":"10.1186/s40001-025-02414-9","url":null,"abstract":"<p><strong>Objectives: </strong>To explore the effect of ligustrazine phosphate tablets combined with cerebroside carnosine on neurological function and serum inflammatory factors among patients with ischemic cerebrovascular disease.</p><p><strong>Methods: </strong>This was a quasi-experimental study. From March 2019 to February 2022, 126 patients were non-randomly divided into control (n = 63) and intervention (n = 63) groups. The control group received routine treatment such as encephaloside and carnosine, while the intervention group was treated with ligustrazine phosphate tablets and brain glycoside carnosine for 2 weeks. Serum S-100β protein, nerve growth factor (NGF), inflammatory factors [tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP)], National Institutes of Health Stroke scale (NIHSS) and and Activities of Daily Living (ADL) scale were assessed before and after the intervention.</p><p><strong>Results: </strong>After treatment, the level of S-100β in the intervention group was lower, and the level of NGF was significantly higher than in the control group. The levels of TNF-α and CRP in the intervention group were reduced. The NIHSS score of the intervention group was lower, and the ADL score was significantly higher than that of the control group.</p><p><strong>Conclusions: </strong>The combination of ligustrazine phosphate tablets with cerebroside carnosine can improve neurological function, alleviate inflammation, and enhance the quality of life, worthy of clinical promotion.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"158"},"PeriodicalIF":2.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585073","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}

{"title":"LncRNA-MALAT1 promotes triple-negative breast cancer progression and function as ceRNA to target REEP5 by sponging miR-106a-5p.","authors":"Qiu-Hui Yang, Ye-Qin Fu, Wei-Liang Feng, Jie-Fei Mao, Ning Xu, Qing Liu, Qian-Jun Yan, Hong-Jian Yang, Xi-Ping Zhang","doi":"10.1186/s40001-025-02420-x","DOIUrl":"10.1186/s40001-025-02420-x","url":null,"abstract":"<p><p>Axillary lymph node metastasis (ALNM) in triple negative breast cancer (TNBC) will lead to poor prognosis. Recent studies have shown that long non-coding RNAs (lncRNAs) were involved in the progression of tumors. This study aimed to explore the role and mechanism of lncRNA-MALAT1 in the progression of TNBC and its relationship with ALNM. MALAT1 is highly expressed in TNBC cells lines, tumor tissues and serum, and it is positively correlated with the degree of ALNM. In addition, MALAT1 can act as a competitive endogenous RNA (ceRNA) that regulates cellular biological behavior by competitively binding to miR-106a-5p with REEP5. In conclusion, our results show that MALAT1 could function as ceRNA promote the proliferation, invasion and metastasis of TNBC cells through MALAT1/miR-106a-5p/REEP5 axis, which is expected to provide new ideas for the diagnosis of TNBC in clinic.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"159"},"PeriodicalIF":2.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585077","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}

{"title":"A novel c.1468 G > A GRN mutation causes frontotemporal dementia in a Chinese Han family.","authors":"Mingrong Xia, Chenhao Gao, Junkui Shang, Dan Li, Ali Yang, Weizhou Zang, Jiewen Zhang","doi":"10.1186/s40001-025-02418-5","DOIUrl":"10.1186/s40001-025-02418-5","url":null,"abstract":"<p><strong>Background/purpose: </strong>GRN mutations act as causative factors in patients with FTD clinical phenotype or FTD pathology and exhibit high clinical heterogeneity. The discovery of these mutations and the analysis of their associations with resembling Alzheimer's disease should be critical to understand the pathogenesis of FTD.</p><p><strong>Methods: </strong>Clinical analysis, neuroimaging, target region capture and high-throughput sequencing were performed in a family of 3 generations. The underlying Alzheimer's pathology was evaluated by using biomarker evidence obtained from cerebrospinal fluid (CSF) amyloid testing, 18F-florbetapir (AV-45) PET imaging and FDG18-positron emission tomography imaging.</p><p><strong>Results: </strong>Through target region capture and high-throughput sequencing, a three-generation family was able to identify a heterozygous G to A point mutation at position 490 (c.1468)G > A, which led to a valine to methionine substitution (V490M) at exon 12. This unique missense mutation was found at codon 1468. Eight members of the proband's family-two sisters and the proband himself-had the mutation found by Sanger sequencing. Interestingly, biomarker tests for amyloid in the proband's cerebrospinal fluid (CSF) indicated pathology consistent with Alzheimer's disease (AD). The mutation was expected to have a high likelihood of being pathogenic.</p><p><strong>Conclusions: </strong>We firstly reported a novel mutation in the GRN gene at codon 490 (V490M) in exon 12 in a China FTD family. The CSF biomarker alterations of the proband revealed a reduction in Aβ42 and the Aβ42/Aβ40 ratio. The analysis of mutation might support the role of GRN in patients with FTD and contribute to the discovery of a new pathological mechanism underlying the disease.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"157"},"PeriodicalIF":2.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11889931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585066","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}