Anhui University of Traditional Chinese Medicine

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have proven effectiveness in stimulating weight loss, as well as enhancing metabolic parameters. Nevertheless, the information available on the possible effects on mood and the risk of depression is not consistent, and it is possible that further research should evaluate the psychiatric safety of GLP-1RA usage. To conduct a systematic review and quantitatively assess whether the usage of GLP-1RA is associated with the increased risk of having depression-related adverse events and to learn more about the sources of heterogeneity. In accordance with the PRISMA guidelines, we systematically searched PubMed, Embase, Cochrane Library, Web of Science, Scopus, and LILACS for randomized controlled trials and observational studies published between 2000 and 2025. Studies were eligible if they enrolled adults with overweight or obesity and reported outcomes related to depression or mood. Random-effects models were used for meta-analysis, with heterogeneity, sensitivity analysis, meta-regression, and publication bias assessments conducted. A total of 19 studies were included in this systematic review. Combined findings revealed that the risk of depression was linked to the utilization of GLP-1RA (OR = 1.49, 95% CI: 1.18–1.88). Between-study heterogeneity was very high (I² = 99.21%) although sensitivity analysis revealed that the findings were robust. The heterogeneity was not explained by a single factor, indicating a multifactor interaction, as found in meta-regression. None of the publications exhibited any considerable bias. The current evidence suggests a possible association between use of GLP-1RA and an increased risk of depression, but overall risk seems to be dominated by population characteristics, drug class, and how mood outcomes are assessed. Given the metabolic benefits of GLP-1RAs, caution is advised in patients with a history of depression or psychiatric vulnerability and a heightened vigilance for these events is warranted. High-quality studies are warranted with psychiatric outcomes as primary endpoints in order to determine whether there is a causal relationship and to identify high-risk subpopulations.

Introduction: This study evaluated the efficacy and safety of combining power bicycle aerobic training with acupuncture in patients with chronic coronary syndrome (CCS). Methods: In this single-center randomized trial, 100 patients with stable CCS [New York Heart Association (NYHA) I–II, left ventricular ejection fraction (LVEF) ≥40%] were allocated to an observation group (power bicycle training plus acupuncture, n = 50) or a control group (power bicycle training alone, n = 50). Both received guideline-directed medical therapy. The intervention comprised three 3-week treatment cycles with 2-week washout periods. Outcomes included LVEF, peak oxygen uptake (VO 2 peak), anaerobic threshold (AT), peak power (PP), 6 min walk distance (6MWD), and Barthel index, assessed at baseline and posttreatment. The combined intervention group demonstrated significantly greater mean improvements from baseline to posttreatment in LVEF (4.73% vs. 1.88%) and 6MWD (88.32 m vs. 73.12 m) compared with the control group. Safety and needling sensation tolerability were monitored. Results: The observation group demonstrated significantly greater improvements in LVEF (62.19 ± 5.01% vs. 59.06 ± 4.77%, P = 0.002) and 6MWD (380.76 ± 13.42 m vs. 367.98 ± 10.65 m, P < 0.001) compared with controls. Superior gains in VO 2 peak, PP, and AT were also observed (all P < 0.05). No serious adverse events occurred, and visual analog scale scores for needling sensation remained low and stable. Conclusion: Power bicycle training combined with acupuncture significantly improves cardiopulmonary function and exercise tolerance in stable CCS patients, with excellent safety and tolerability. Acupuncture may serve as a beneficial adjunct to conventional aerobic exercise in cardiac rehabilitation.

Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), a mitochondrial bifunctional enzyme, is reportedly upregulated in several malignancies, demonstrating cancer-associated dysregulation. However, its functional contribution to oral squamous cell carcinoma (OSCC) progression remains unexplored. Therefore, this study aimed to investigate the role of MTHFD2 in OSCC development. MTHFD2 expression was assessed in OSCC biospecimens using integrated bioinformatics, immunohistochemistry, and immunoblotting techniques. Survival analysis was conducted utilizing the Kaplan–Meier methodology. The MTHFD2-associated mechanisms involved in OSCC were explored via enrichment analysis. Genetic suppression of MTHFD2 was employed to evaluate the functional consequences on OSCC cell proliferation (Cell Counting Kit-8 assay), apoptosis (flow cytometry), migration (wound healing assay), and invasion (Matrigel transmigration). MTHFD2 expression was considerably elevated in OSCC lesions and cellular models. MTHFD2 overexpression in OSCC tissues correlated with advanced Tumor, Node, and Metastasis stage (P = 0.002), regional lymph node metastasis (P = 0.043), and elevated Ki67 expression (P < 0.001). Furthermore, increased MTHFD2 levels were associated with poor overall survival outcomes in patients with OSCC (P < 0.05). Pathway enrichment analysis revealed that MTHFD2 upregulation was closely linked to the dysregulation of key neoplastic processes. Stable MTHFD2 depletion attenuated cell proliferation in vitro and diminished xenograft tumorigenicity in vivo (P < 0.05). Additionally, MTHFD2 ablation induced OSCC cell apoptosis and reduced cell migration and invasion. This study indicates that MTHFD2 is critical for OSCC progression and may serve as a potential therapeutic target, though further validation is needed to confirm its independent prognostic value and clinical applicability.

Backgrounds: Given the distinct pathogenic mechanisms of early-onset Alzheimer’s disease (EOAD) and late-onset Alzheimer’s disease (LOAD), identifying disease-specific therapeutic targets for each subtype is particularly critical. Methods: We performed proteome-wide Mendelian randomization (MR), colocalization analysis, summary-data-based MR, and Heterogeneity in Dependent Instruments (HEIDI) tests to identify the causal roles of candidate proteins in EOAD and LOAD. Further analyses included protein-protein interaction network analysis, GO/KEGG enrichment analyses, and single-cell RNA sequencing annotation. Druggability evaluation of the target proteins, Phenome-wide association study was conducted to systematically evaluate the potential adverse effects associated with druggable proteins. High-throughput molecular docking and molecular dynamics simulations were conducted to target the top therapeutic targets. Results: Genetically predicted levels of three proteins (APOE, NECTIN2, and PVR) were associated with EOAD risk, nine proteins (APOE, NECTIN2, PVR, EPHB4, SEMA3F, RNASET2, BTN1A1, PSAPL1, and GRN) were associated with LOAD risk, three proteins (APOE, NECTIN2, and PVR) were colocalized with EOAD, and six proteins (APOE, NECTIN2, PVR, SEMA3F, BTN1A1, and EPHB4) were colocalized with LOAD. Three of the proteins (APOE, NECTIN2, and PVR) serve as common targets for both EOAD and LOAD. EPHB4 and BTN1A1 were prioritized for LOAD with the most convincing evidence. The small molecule cucurbit[8]uril exhibits excellent binding affinity with both EPHB4 and BTN1A1 target proteins for the treatment of Alzheimer’s disease. Conclusions: This study pinpointed APOE, NECTIN2, and PVR as shared therapeutic targets for EOAD and LOAD, and EPHB4 and BTN1A1 singled out as a priority target for LOAD.