The role of immune cell signatures in the pathogenesis of ovarian-related diseases: a causal inference based on mendelian randomization.

BACKGROUND: Immune cells play a pivotal role in maintaining ovarian function. However, the specific contributions of different immune cell phenotypes to the pathogenesis of specific ovarian-related diseases remain poorly understood. We aim to investigate the correlation between 731 immunophenotypes and ovarian-related diseases. MATERIALS AND METHODS: Utilizing publicly available genetic data, we undertook a series of quality control measures to identify instrumental variables (IVs) associated with exposure. Subsequently, we conducted two-sample Mendelian randomization (MR) using inverse variance weighting to explore the causal relationships between 731 immune cell features and six ovarian-related diseases: ovarian cysts, ovarian dysfunction, premature ovarian failure (POF), polycystic ovary syndrome (PCOS), benign neoplasm of ovary, and malignant neoplasm of ovary at the genetic level. Sensitivity analyses, including leave-one-out and other MR analysis models, were performed. Finally, Bayesian colocalization (COLOC) analysis was employed to identify specific co-localized genes, thereby validating the MR results. RESULTS: At the significance level corrected by Bonferroni, four immune phenotypes, including CD25 on IgD- CD38- B cells, were associated with ovarian cysts; four immune phenotypes, including CD39+ CD4+ T cell Absolute Count, were associated with ovarian dysfunction; eight immune phenotypes, including SSC-A on HLA DR+ CD8+ T cells, were associated with POF; five immune phenotypes, including CD20- CD38- B cell Absolute Count, were associated with PCOS; five immune phenotypes, including CD4+ CD8dim T cell Absolute Count, were associated with benign ovarian tumors; and three immune phenotypes, including BAFF-R on IgD- CD38+ B cells, were associated with malignant ovarian tumors. Sensitivity analysis indicated robust results. COLOC analysis identified four immune cell co-localized variants (rs150386792, rs117936291, rs75926368, rs575687159) with ovarian diseases. CONCLUSION: Our study elucidates the close genetic associations between immune cells and six ovarian-related diseases, thereby providing valuable insights for future research endeavors and clinical applications.

Advances of NOTCH2NLC Repeat Expansions and Associated Diseases: A Bibliometric and Meta-analysis.

The unclear pathogenic mechanisms of neurodegenerative disorders stemming from NOTCH2NLC GGC repeat expansions drive focused research. Thus, a bibliometric and meta-analysis was conducted to uncover research trends and positivity rates in NOTCH2NLC. We conducted systematic searches in the Web of Science, PubMed, Embase, and Scopus databases for studies related to NOTCH2NLC up until August 2, 2023. Information regarding countries, institutions, authors, journals, and keywords of studies included in the Web of Science was analyzed and visualized. The positivity rates of NOTCH2NLC GGC repeat expansions across all screened patients and patients' families were pooled under the random-effects model. Publication bias and its impact were examined using funnel plots, Egger's linear regression, and trim-and-fill method. The bibliometric analysis, revealing pronounced publication growth, comprised 119 studies, which came from China and Japan particularly. "Neuronal intranuclear inclusion disease" emerged as a frequently used keyword. The meta-analysis comprised 36 studies, indicating global positivity rates of 1.79% (95% CI, 0.75-3.17) for all patients and 2.00% (95% CI, 0.26-4.78) for patients' families. Subgroup analyses based on region and phenotype suggested the highest NOTCH2NLC positivity rates in Taiwan population (5.42%, 95% CI 0.08-16.89) and in leukoencephalopathy-dominant patients (8.25%, 95% CI, 3.01-15.60). Sensitivity analysis affirmed the robustness of results. In conclusion, NOTCH2NLC GGC repeat expansions exhibit rare globally, primarily in East Asia, and leukoencephalopathy-dominant patients, emphasizing regional and phenotypic distinctions. Emerging focal points in NOTCH2NLC researches underscore the need for collaborative exploration.

Pegbelfermin for reducing transaminase levels in patients with non-alcoholic steatohepatitis: a dose-response meta-analysis of randomized controlled trials.

Background: The efficacy of Pegbelfermin (PGBF) in treating non-alcoholic steatohepatitis (NASH) remains controversial. Therefore, we conducted a dose-response meta-analysis to explore the effect and pattern of PGBF at different dosages and treatment durations on transaminase reduction in NASH patients. Methods: We conducted searches on PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov, and supplemented the search with gray literature and manual searches. Randomized controlled trials (RCTs) evaluating the efficacy of PGBF in NASH patients were included. Risk of bias was assessed by Cochrane Risk of Bias Tool 2.0. We used random-effects models, generalized least squares regression, constrained maximum likelihood, and restricted cubic splines to explore the dose-response relationship. Egger's linear regression was employed to assess publication bias. The study is registered with PROSPERO, CRD42023448024. Results: Four RCT studies from the period 2018-2023, involving 546 participants, were included. No participants discontinued PGBF treatment due to adverse events. High-dose PGBF treatment significantly reduced transaminase levels in NASH patients compared to the low-dose group (ALT %: MD = 14.94, 95% CI = 2.11-27.77; AST %: MD = 9.05, 95% CI = 3.17-14.92). Longer treatment duration further decreased transaminase levels (ALT%: MD = 8.81, 95% CI = 4.07-13.56; AST%: MD = 6.72, 95% CI = 2.62-10.81). Egger's test did not reveal significant publication bias (p > 0.05). Further investigation indicated a ceiling effect of PGBF dosage on transaminase reduction at 30 mg/week, and NASH patients experienced a rebound in transaminase levels after 28 weeks of continuous treatment. Conclusion: There is a positive correlation between PGBF dosage and transaminase reduction within a certain range, showing an overall non-linear dose-response relationship. This finding provides guidance for the clinical application of PGBF. Clinicians should be mindful of the dosage ceiling at 30 mg/week and monitor changes in transaminase levels after 28 weeks for timely adjustments in PGBF dosage. Systematic review registration: PROSPERO, CRD42023448024. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=448024.

Causality between Ankylosing Spondylitis and osteoarthritis in European ancestry: a bidirectional Mendelian randomization study.

Objective: To explore the bidirectional causal relationship between Ankylosing Spondylitis (AS) and Osteoarthritis (OA) at the genetic level within the European ancestry. Methods: We implemented a series of quality control steps to select instrumental variables (IVs) related to the exposure. We conducted two-sample Mendelian randomization (MR) using the inverse-variance weighted method as the primary approach. We adjusted significance levels using Bonferroni correction, assessed heterogeneity using Cochrane's Q test. Sensitivity analysis was conducted through leave-one-out method. Additionally, external datasets and relaxed IV selection criteria were employed, and multivariate MR analyses were performed for validation purposes. Finally, Bayesian colocalization (COLOC) analysis identified common genes, validating the MR results. Results: The investigation focused on the correlation between OA and AS in knee, hip, and hand joints. MR results revealed that individuals with AS exhibit a decreased risk of knee OA (OR = 0.9882, 95% CI: 0.9804-0.9962) but no significant increase in the risk of hip OA (OR = 0.9901, 95% CI: 0.9786-1.0018). Conversely, AS emerged as a risk factor for hand OA (OR = 1.0026, 95% CI: 1.0015-1.0036). In reverse-direction MR analysis, OA did not significantly influence the occurrence of AS. Importantly, minimal heterogeneity was observed in our MR analysis results (p > 0.05), and the robustness of these findings was confirmed through sensitivity analysis and multivariate MR analysis. COLOC analysis identified four colocalized variants for AS and hand OA (rs74707996, rs75240935, rs181468789, and rs748670681). Conclusion: In European population, individuals with AS have a relatively lower risk of knee OA, whereas AS serves as a risk factor for hand OA. However, no significant causal relationship was found between AS and hip OA. Additionally, it offers novel insights into genetic research on AS and OA.

The prevalence and risk of depression in aged COVID-19 survivors: a bibliometric and meta-analysis.

To explore depression prevalence and related risk factors among elderly coronavirus disease 2019 (COVID-19) survivors, while also evaluating research characteristics. We searched Web of Science, PubMed, Embase, Scopus, CNKI and Wanfang Data for studies that reported COVID-19 and depression in older adults. 'Bibliometrix' facilitated bibliometric analysis and information visualisation. Random-effects models merged depression prevalence and relevant risks. Publication bias and its impact were examined using funnel plots, Begg's test, Egger's linear regression, and trim-and-fill method. Meta-regression, bubble plots, and Baujat plots probed heterogeneity. Sensitivity analysis applied the leave-one-out method. The study is registered with PROSPERO, CRD42023417706. The bibliometric analysis comprised 138 studies. Publication frequency peaked in the US, China, and Italy, reflecting significant growth. The meta-analysis comprised 43 studies. Elderly COVID-19 patients exhibit 28.33% depression prevalence (95% CI: 21.24-35.97). Severe cases (43.91%, 95% CI: 32.28-55.88) experienced higher depression prevalence than mild cases (16.45%, 95% CI: 11.92-21.50). Sex had no depression prevalence impact based on bubble plots. Notably, depression risk did not significantly differ between elderly and young COVID-19 patients (odds ratio (OR) = 1.1808, 95% CI: 0.7323-1.9038). However, COVID-19 infection emerged as a substantial elderly depression risk factor (OR = 1.8521, 95% CI: 1.2877-2.6639). Sensitivity analysis confirmed result robustness. Elderly COVID-19 survivors are likely to develop depression symptoms with regional variations. Severe cases are associated with heightened depression prevalence. COVID-19 infection stands out as a key elderly depression risk factor, while sex does not influence prevalence. The field's expansion necessitates sustained collaboration and extensive research endeavours.

Research progress of ferroptosis in Parkinson's disease: a bibliometric and visual analysis.

Background: In recent years, the role of ferroptosis in Parkinson's disease (PD) has become a research hotspot based on evidence of abnormal iron deposition and lipid peroxidation damage in the brains of PD patients. This study aims to examine the relevant research on ferroptosis and PD from a bibliometric perspective. Methods: Original research and review articles related to ferroptosis and PD were retrieved from the Web of Science Core Collection (WOSCC) database. Statistical analysis and visualization of information including countries, institutions, authors, journals, and keywords of the included studies were conducted using the R software package "bibliometrix." Results: A total of 414 articles met the inclusion criteria, averaging 37.86 citations per article. From 2012 to 2022, the average annual growth rate of research in this area was 63.44%. The corresponding authors of published articles were mainly affiliated with institutions in China, the United States, and Australia. Shanghai Jiao Tong University in China and the University of Melbourne in Australia emerged as the most active and influential institutions. The journal with the highest H-index and publication output was Free Radical Biology and Medicine. "Ferroptosis," "immunotherapy," "prognosis" and "microenvironment" were identified as high-frequency keywords, indicating current and future research directions in this field. Conclusion: This bibliometric study provides insights into current research hotspots and emerging trends in the growing field of ferroptosis research related to PD. The high-frequency keywords identified highlight active areas of investigation involving methods, mechanisms, and populations of interest.