American journal of translational research最新文献

{"title":"Explainable machine learning-based multiphase contrast-enhanced CT radiomics for noninvasively predicting GPC3 expression in hepatocellular carcinoma: a bicentric study.","authors":"Wangwang Lin, Changkai Chen, Xue Wang","doi":"10.62347/IVMH4590","DOIUrl":"10.62347/IVMH4590","url":null,"abstract":"<p><strong>Objectives: </strong>Accurate pre-operative prediction of Glypican-3 (GPC3) profiles in hepatocellular carcinoma (HCC) is essential for selecting candidates for targeted therapy and individualized treatment. This study aimed to develop and externally validate an explainable machine learning model for noninvasively prediction of GPC3 expression in HCC.</p><p><strong>Methods: </strong>A total of 301 HCC patients were retrospectively enrolled from two centers (Center 1: 241; Center 2: 60) between January 2016 and September 2024. Radiomics features were extracted from arterial (AP), portal venous (PVP), and delayed phase (DP) images. Robust features were selected via a sequential pipeline including interobserver agreement screening (intraclass correlation coefficient [ICC] > 0.8), Spearman correlation analysis (Ρ > 0.85), and recursive feature elimination (RFE). Single-phase (AP, PVP, DP), combined-phase (APD) radiomics, clinical, and clinical-radiomics models were constructed. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), and SHAP analysis was applied for model interpretability.</p><p><strong>Results: </strong>The combined clinical-radiomics model outperformed the clinical model, achieving an AUC of 0.886 in the training cohort, 0.880 during internal validation cohort, and 0.839 during external validation cohort (P < 0.05). The APD radiomics model showed performance non-inferior to that of the combined model (P > 0.05) and outperformed all single-phase models. AFP > 7 ng/mL (OR=3.257) and intratumoral necrosis (OR=2.947), as confirmed by multivariate logistic regression, were independent predictors for GPC3 positivity. SHAP analysis further identified radiomics score as the most influential predictor (mean |SHAP|=1.84).</p><p><strong>Conclusion: </strong>The multiphase CECT radiomics-based combined model demonstrates good cross-center generalizability and enables accurate noninvasive prediction of GPC3 expression status in HCC. This model may provide a reliable imaging-based tool for screening candidate patients for GPC3-targeted therapies.</p>","PeriodicalId":7731,"journal":{"name":"American journal of translational research","volume":"18 8","pages":"7259-7270"},"PeriodicalIF":1.8,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13590986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FCGBP promotes malignant phenotypes of glioblastoma cells via activation of the TGF-β1 signaling pathway.","authors":"Jinning Zhang, Lingtong You, Junhuai Wei, Xinyao Chen, Huangqiang Yang, Jiaxin Huang, Huihang Wang, Zhixian Jiang","doi":"10.62347/NVYV1514","DOIUrl":"10.62347/NVYV1514","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the expression level of IgG Fc-binding protein (FCGBP) in glioma cells, elucidate its role in malignant tumor phenotypes, and explore its relationship with the transforming growth factor-β (TGF-β) signaling pathway.</p><p><strong>Methods: </strong>The expression of FCGBP was compared between primary human astrocytes (HA) and glioma cell lines (U87, U251, LN229, and T98G). FCGBP was then silenced in U87 cells. Cell proliferation, migration, and invasion were assessed using Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine (EdU) incorporation, colony formation, wound healing, and Matrigel-coated Transwell assays. Apoptosis and cell-cycle distribution in U87 cells were analyzed by flow cytometry. Co-immunoprecipitation (Co-IP) was performed to validate the endogenous association between FCGBP and TGF-β1-containing protein complexes. Rescue experiments were conducted using recombinant TGF-β1 protein. Additionally, the in vitro findings were further validated in nude mouse xenograft models.</p><p><strong>Results: </strong>FCGBP was highly expressed in various glioma cell lines, and its knockdown reduced TGF-β levels in the culture supernatant. Knockdown of FCGBP in U87 cells significantly suppressed malignant behaviors, including proliferation, migration, and invasion, while inducing apoptosis and cell-cycle arrest. Co-IP assays suggested an endogenous association between FCGBP and TGF-β1-containing protein complexes, and treatment with recombinant TGF-β1 effectively reversed the inhibitory effects of FCGBP knockdown. <i>In vivo</i> experiments confirmed that silencing FCGBP markedly inhibited tumor growth in nude mice and significantly reduced systemic inflammation and TGF-β levels.</p><p><strong>Conclusion: </strong>FCGBP promotes malignant phenotypes in glioma cells (U87) and accelerates tumor growth <i>in vivo</i>, potentially through activation of the TGF-β/Smad signaling pathway.</p>","PeriodicalId":7731,"journal":{"name":"American journal of translational research","volume":"18 8","pages":"6550-6567"},"PeriodicalIF":1.8,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13590671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role and mechanism of CHST6-mediated lactation modification in lenvatinib resistance in hepatocellular carcinoma cells.","authors":"Dongdong Wang, Hongqiang Gao, Li Li","doi":"10.62347/JQSF1666","DOIUrl":"10.62347/JQSF1666","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is the 3rd leading cause of cancer-related death. Approximately 70% of HCC patients present with advanced-stage disease at the time of diagnosis. Lenvatinib is a standard first-line treatment for HCC; however, the development of drug resistance substantially limits its therapeutic efficacy.</p><p><strong>Methods: </strong>Genes associated with lactylation and lenvatinib resistance were identified through bioinformatic analyses. Differentially expressed genes (DEGs) were screened using data from the TCGA-LIHC cohort, the GSE186191 dataset, and a lactylation-related gene datasets. Receiver operating characteristic (ROC) curve analysis, Cox regression analysis, survival analysis, and prognostic evaluation were performed to analyze the association between identified genes and treatment outcomes. After constructing the lenvatinib-resistant MHCC97 cell line (MHCC97-LR) was established, and the effects of CHST6 knockdown on cell viability, apoptosis, cell cycle, lactate content, and the expression of lactylation-related genes were analyzed.</p><p><strong>Results: </strong>A total of 15 overlapping DEGs related to both lactylation and lenvatinib resistance were identified. These genes were involved in multiple metabolic pathways, including lipid and glucose metabolism. CHST6, SPAG4, and PFKFB4 exhibited excellent diagnostic performance for HCC, and their lower expression levels were correlated with favorable prognosis. Cox regression analysis identified CHST6 as the only gene significantly associated with HCC prognosis, demonstrating predictive value for 1-5-year survival in HCC patients. Strikingly, enhanced lactylation was associated with elevated CHST6 expression and greater cell viability in MHCC97-LR cells. Furthermore, CHST6 knockdown reduced the lactate production and the expression of lactylation-associated proteins (Pan-Kla, H3K18la, and H3K56la) in MHCC97-LR cells, along with increased apoptosis and G1-phase cell-cycle arrest in MHCC97-LR cells.</p><p><strong>Conclusion: </strong>CHST6 knockdown reduces intracellular lactate contents and lactylation in MHCC97-LR cells, thereby attenuating lenvatinib resistance and enhancing the antitumor efficacy of lenvatinib in HCC.</p>","PeriodicalId":7731,"journal":{"name":"American journal of translational research","volume":"18 8","pages":"6612-6626"},"PeriodicalIF":1.8,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13590760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overweight and obesity are associated with poorer treatment response and impaired pulmonary function in children with bronchial asthma: a retrospective study.","authors":"Bingjie Wang, Juan Huang, Xiangteng Liu, Jiabiao Lin, Qiao Liang, Bo Wang, Guilan Wang","doi":"10.62347/FEMJ5128","DOIUrl":"10.62347/FEMJ5128","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the effect of body mass index (BMI) on standardized treatment efficacy and pulmonary function in children with bronchial asthma.</p><p><strong>Methods: </strong>Clinical data of 120 children with acute asthma attacks (January 2020-December 2023) were retrospectively analyzed. Children were divided into a normal-weight group (16th- < 85th percentile, n=62) and an overweight/obese group (≥ 85th percentile, n=58). Both received standardized treatment. Clinical efficacy, CACT scores, annual attack frequency, emergency visits, inflammatory markers, and pulmonary function were compared.</p><p><strong>Results: </strong>The normal weight group showed significantly higher total effective rate (93.5% vs. 79.3%, P=0.022), better CACT scores post-treatment (23.5 ± 2.8 vs. 19.8 ± 3.2, P < 0.001), and fewer annual attacks (3.2 ± 1.5 vs. 5.6 ± 1.8, P < 0.001) and emergency visits (1.8 ± 1.0 vs. 3.4 ± 1.3, P < 0.001). Both groups improved in pulmonary function and inflammatory factors (all P < 0.05), but the improvement rates in FEV₁ (23.5 ± 7.2% vs. 31.7 ± 8.5%), FEV₁/FVC (13.1 ± 4.8% vs. 17.9 ± 5.6%), PEF (25.7 ± 7.5% vs. 35.7 ± 9.2%), and FEF50% (5.2 ± 4.5% vs. 27.9 ± 7.8%) were significantly lower in the overweight/obese group (all P < 0.05).</p><p><strong>Conclusion: </strong>Overweight and obesity are associated with poorer treatment response, less pulmonary function improvement, and worse disease control in asthmatic children. Weight management should be emphasized in this population to optimize therapeutic outcome.</p>","PeriodicalId":7731,"journal":{"name":"American journal of translational research","volume":"18 8","pages":"7107-7117"},"PeriodicalIF":1.8,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13590975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liraglutide in combination with zoledronic acid and calcium carbonate and vitamin D3 for diabetic osteoporosis: efficacy and glycometabolism impact.","authors":"Zhen Wu, Jinchan Guo, Qinghe Liu, Jinting Jiang, Bohan Li","doi":"10.62347/KQUI1289","DOIUrl":"10.62347/KQUI1289","url":null,"abstract":"<p><p>This study focuses on people with diabetic osteoporosis (DOP), exploring the efficacy of triple therapy with liraglutide (LIR), zoledronic acid (ZOL) and Calcium Carbonate and Vitamin D3 (CCD3) and the impact of this regimen on glycometabolism (GM). Ninety-nine eligible DOP patients visiting our hospital (January 2023-December 2025) were selected and assigned to a control group (n=46; receiving ZOL + CCD3) and a research group (n=53; receiving LIR + ZOL + CCD3) based on their treatment regimen. Between-group comparisons were made regarding of: efficacy, electrolyte metabolism (calcium [Ca], phosphorus [P]); bone metabolism (bone-specific alkaline phosphatase [BALP], secreted frizzled-related protein 5 [SFRP5], β-C-terminal telopeptide of type 1 collagen [β-CTX]), GM (glycosylated hemoglobin [HbA1c], fasting plasma glucose [FPG], fasting insulin [FINS]), glycemic variability (mean/largest amplitude of glycemic excursion [MAGE/LAGE], coefficient of variation [CV]), hepatorenal function (alanine aminotransferase [ALT], serum creatinine [SCr]), inflammatory cytokines (interleukin [IL]-6, IL-8, tumor necrosis factor-α [TNF-α]) and adverse drug reactions (ADRs; flatulence, nausea, fatigue, abdominal pain and fever). The analysis results showed that compared with controls, the total effective rate of the research group was increased, Ca, BALP and SFRP5 were elevated and the post-medication P, β-CTX, GM indices, glycemic variability parameters and inflammatory markers were decreased (P<0.05). No significant changes in hepatorenal function were observed within (pre- vs. post-treatment) or between groups. The total ADR rate was equivalent across the groups. It is suggested that concomitant administration of LIR, ZOL and CCD3 can significantly improve curative efficacy and ameliorate GM in DOP patients without compromising hepatorenal function.</p>","PeriodicalId":7731,"journal":{"name":"American journal of translational research","volume":"18 8","pages":"7297-7305"},"PeriodicalIF":1.8,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13590999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction of acute metabolic complications in hospitalized elderly patients with type 2 diabetes using admission HbA1c and hypertension: a retrospective cohort study.","authors":"Chunqiang Chen, Suxia Hu, Xiaoqin Zhu, Zhenzhen Xie, Yifei Zhu","doi":"10.62347/QQCR9025","DOIUrl":"10.62347/QQCR9025","url":null,"abstract":"<p><strong>Objective: </strong>To identify admission-based predictive indicators for in-hospital acute metabolic complications in elderly patients with type 2 diabetes mellitus (T2DM), and to develop and internally validate a simple predictive model for early risk stratification.</p><p><strong>Methods: </strong>A total of 203 elderly inpatients with T2DM were included in this retrospective cohort study. According to the occurrence of acute metabolic complications during hospitalization, patients were divided into a complication group (n = 40) and a non-complication group (n = 163). All candidate predictive indicators were collected from admission medical records and laboratory test results obtained within 24 to 48 hours after admission. Univariate and multivariate logistic regression analyses were performed to screen for independent predictive factors. The model's discriminatory power was evaluated using the area under the receiver operating characteristic curve (AUC), and 1000 bootstrap resamplings were adopted for internal validation.</p><p><strong>Results: </strong>The complication group had significantly higher admission HbA1c levels than the non-complication group (P<0.001), as well as a higher prevalence of hypertension (P = 0.002). Multivariate regression analysis verified that HbA1c (OR = 1.761, 95% CI: 1.44-2.15, P<0.001) and hypertension (OR = 3.904, 95% CI: 1.60-9.53, P = 0.003) were independent risk factors for in-hospital acute metabolic complications. The predictive model based on these two indicators exhibited good discriminatory performance, with an original AUC of 0.836. After bootstrap internal validation, the optimism-corrected AUC was 0.726, indicating acceptable stability of the model.</p><p><strong>Conclusion: </strong>Elevated admission HbA1c and comorbid hypertension are independent predictive factors for in-hospital acute metabolic complications in elderly T2DM patients. This novel simple model has favorable predictive efficacy and stability, and it can serve as a feasible clinical tool for early risk stratification in elderly T2DM inpatients.</p>","PeriodicalId":7731,"journal":{"name":"American journal of translational research","volume":"18 8","pages":"6672-6681"},"PeriodicalIF":1.8,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13590721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repeated low-intensity red light combined with defocus-incorporated multiple segments (DIMS) spectacles for controlling myopia progression in children.","authors":"Wubo Cheng, Xianglong Yi","doi":"10.62347/JGQF1692","DOIUrl":"10.62347/JGQF1692","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the efficacy and safety of repeated low-intensity red light (RLRL) therapy combined with defocus incorporated multiple segments (DIMS) spectacles for controlling myopia progression in children.</p><p><strong>Methods: </strong>In this retrospective cohort study, medical records of 100 children with persistent myopia progression despite DIMS spectacle wear were reviewed. Patients were divided into two groups based on their treatment history: a DIMS-only control group (n=50) and an RLRL+DIMS combination group (n=50). Axial length (AL), spherical equivalent refraction (SER), uncorrected visual acuity (UCVA), central retinal thickness (CRT), subfoveal choroidal thickness (SFChT), corneal curvature (CC), fundus autofluorescence, adverse events were assessed at baseline and 1, 3, 6, 9 and 12 months.</p><p><strong>Results: </strong>Of the 100 enrolled children, 92 completed the 12-month follow-up. Baseline characteristics were comparable between groups (all P>0.05). At 12 months, the combination group showed significantly less axial elongation than the control group (mean change: 0.060±0.237 mm vs. 0.386±0.183 mm, P<0.001), with 37.8% of children showing axial shortening. SER progression was also significantly slower in the combination group (change: +0.038±0.435 D vs. -0.720±0.295 D; P<0.001). SFChT increased significantly in the combination group (+13.2±27.4 μm) but decreased in controls (-3.3±12.4 μm, P<0.001). No significant changes in CRT or CC were observed. Transient glare occurred in nine children; one child withdrew due to an 8-minute afterimage. No abnormal fundus autofluorescence was detected.</p><p><strong>Conclusion: </strong>RLRL combined with DIMS spectacles effectively increased choroidal thickness, delayed axial elongation, and slowed SER progression in myopic children over 12 months, with a favorable short-term safety profile. Longer-term studies are warranted to confirm sustained efficacy and safety.</p>","PeriodicalId":7731,"journal":{"name":"American journal of translational research","volume":"18 8","pages":"7141-7162"},"PeriodicalIF":1.8,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13590974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of CDC42 in adenomyosis reduces the proliferation of endometrial stromal cells and the migration of epithelial cells.","authors":"Jia Huang, Huifeng Chen, Zengming Li, Ziyu Zhang, Yunna Qin, Liqun Wang","doi":"10.62347/ACDY5165","DOIUrl":"10.62347/ACDY5165","url":null,"abstract":"<p><strong>Objectives: </strong>Adenomyosis severely impairs fertility and quality of life. This study investigated the pathophysiologic role of cell division cycle 42 (CDC42) in adenomyosis by profiling its expression, identifying its binding partners, and performing functional assays on endometrial cells.</p><p><strong>Methods: </strong>Immunofluorescence was used to evaluate CDC42 expression in endometrial cells from adenomyosis patients. RNA sequencing (RNA-seq) was used to analyze transcriptomic changes following CDC42 knockdown. The effects of CDC42 inhibition on endometrial stromal cell proliferation and migration were assessed using cell viability and migration assays. Furthermore, coimmunoprecipitation coupled with mass spectrometry (Co-IP/MS) was conducted to identify CDC42-interacting proteins. Finally, conditioned medium from CDC42-knockdown stromal cells was used to evaluate the effects of paracrine signaling on endometrial epithelial cell migration.</p><p><strong>Results: </strong>CDC42 expression was significantly upregulated in the endometrial cells of adenomyosis patients. Transcriptomic analysis revealed that CDC42 knockdown downregulated the expression of genes associated with the cell cycle and cytokine signaling. Functionally, CDC42 inhibition markedly reduced stromal cell proliferation and attenuated the migration of both stromal and epithelial cells. Notably, conditioned medium from CDC42-knockdown cells also suppressed epithelial cell migration. Co-IP/MS revealed 70 CDC42-interacting proteins, and subsequent Gene Ontology (GO) enrichment analysis indicated their primary involvement in mRNA metabolism, cell adhesion, and Rho GTPase signaling pathways.</p><p><strong>Conclusions: </strong>CDC42 contributes to the pathogenesis of adenomyosis by promoting endometrial stromal cell proliferation and epithelial cell migration, likely by mediating cell cycle regulation and Rho GTPase signaling networks. Therefore, targeting CDC42 is a promising therapeutic strategy for the management of adenomyosis.</p>","PeriodicalId":7731,"journal":{"name":"American journal of translational research","volume":"18 8","pages":"7449-7462"},"PeriodicalIF":1.8,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13590995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amiodarone-metoprolol co-administration enhances heart rate variability and suppresses inflammatory cytokines in tachyarrhythmia patients.","authors":"Xiaoru Han, Zhilan Xin","doi":"10.62347/HYYS9933","DOIUrl":"10.62347/HYYS9933","url":null,"abstract":"<p><strong>Objective: </strong>To elucidate the efficacy of amiodarone (AMD)-metoprolol (MET) co-administration in tachyarrhythmia patients, and to assess its impact on heart rate (HR) variability (HRV) and serum inflammatory cytokines (SICs).</p><p><strong>Methods: </strong>This study included 188 tachyarrhythmia patients who were treated at the Qinghai Provincial Fourth People's Hospital, including 88 patients treated with AMD (control group) and 100 patients treated with AMD+MET (research group). We compared the following clinical data between groups: curative effects, frequency and duration of arrhythmia episodes, vital signs, cardiac function (left ventricular [LV] ejection fraction [LVEF], LV systolic diameter [LVSD], LV end-diastolic diameter [LVEDD]), HRV, SICs, oxidative stress (superoxide dismutase [SOD], malondialdehyde [MDA]), and side effects. In addition, we explored factors influencing patients' curative effects.</p><p><strong>Results: </strong>A higher total effective rate was observed in the research group compared with the control group (91.00% vs. 79.55%, P=0.025). In addition, the research group experienced fewer arrhythmia episodes with shorter durations (P<0.001), and a lower incidence of total adverse events (9.00% vs. 23.86%, P=0.006). A more pronounced drop in post-treatment vital signs, LVSD, LVEDD, various SICs, and MDA (all P<0.001), as well as a rise in LVEF (P<0.001), HRV indices (P<0.001), and SOD (P=0.002), were determined in the research group. LVEF, SDNN, and LF at baseline, as well as therapeutic method, independently influenced patients' efficacy.</p><p><strong>Conclusion: </strong>AMD in combination with MET yields superior efficacy in tachyarrhythmia patients, significantly improving HRV and suppressing SICs.</p>","PeriodicalId":7731,"journal":{"name":"American journal of translational research","volume":"18 8","pages":"6700-6711"},"PeriodicalIF":1.8,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13590674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FBXO11 and FBXO32 are associated with TRAF3-TBK1-IRF3 signaling components in chronic hepatitis B: evidence from clinical samples and preliminary mechanistic studies.","authors":"Liqiang Li, Shun Tao, Yunfei Zhang, Zihan Zeng, Liang Li, Jun Zhang","doi":"10.62347/SCRE1263","DOIUrl":"10.62347/SCRE1263","url":null,"abstract":"<p><strong>Background: </strong>Chronic hepatitis B (CHB) remains a major global health burden despite the availability of effective vaccines and antiviral therapies. F-box proteins have been implicated in diverse biological processes, including immune regulation, but the potential involvement of FBXO11 and FBXO32 in host responses to HBV infection remains poorly understood.</p><p><strong>Aim: </strong>To investigate the expression patterns of FBXO11 and FBXO32 in CHB patients and explore their potential associations with components of the TRAF3-TBK1-IRF3 signaling pathway.</p><p><strong>Methods: </strong>We examined the expression levels of FBXO11 and FBXO32 in PBMCs derived from 30 CHB patients and controls. Protein-protein interactions were evaluated using co-immunoprecipitation and immunofluorescence assays in HEK293T cells. The effects of neddylation inhibition on protein expression and complex formation were examined using MLN4921 treatment. CRISPR/Cas9-mediated gene disruption and adeno-associated virus-mediated overexpression approaches were used for exploratory mechanistic studies. An HBV hydrodynamic injection mouse model was utilized to assess in vivo expression patterns.</p><p><strong>Results: </strong>FBXO11 and FBXO32 expression levels were significantly elevated in PBMCs from CHB patients compared with healthy controls and were accompanied by increased expression of TRAF3-TBK1-IRF3 pathway-related molecules. Co-immunoprecipitation analyses demonstrated associations of FBXO11 and FBXO32 with TRAF3, TBK1, and IRF3 in both clinical samples and HEK293T cells. Reciprocal enhancement of FBXO11 and FBXO32 expression was observed under overexpression conditions. Inhibition of neddylation reduced FBXO11 and FBXO32 protein abundance and weakened their associations with TRAF3-TBK1-IRF3 pathway components. In vivo experiments showed that HBV exposure was accompanied by increased hepatic expression of FBXO11 and FBXO32, and that genetic manipulation effectively altered their expression levels.</p><p><strong>Conclusion: </strong>FBXO11 and FBXO32 are upregulated in CHB and exhibit associations with components of the TRAF3-TBK1-IRF3 signaling network. These findings provide preliminary evidence supporting potential involvement of FBXO11 and FBXO32 in host immune-related signaling during HBV infection and warrant further investigation in physiologically relevant HBV infection models.</p>","PeriodicalId":7731,"journal":{"name":"American journal of translational research","volume":"18 8","pages":"7034-7052"},"PeriodicalIF":1.8,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13590967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015259","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}