To evaluate the safety and efficacy of Edaravone-Dexborneol as a neuroprotective agent in patients with acute ischemic stroke (AIS). We conducted a comprehensive search in PubMed, Scopus, Web of Science, and Cochrane CENTRAL until January 22, 2026, including clinical trials and observational studies comparing Edaravone-Dexborneol with Edaravone monotherapy, standard treatment, and placebo. Data on functional recovery (Modified Rankin Scale [mRS], National Institutes of Health Stroke Scale [NIHSS], Barthel Index [BI]), safety outcomes, and mortality were extracted. A random effects model was used for statistical analysis. Overall, 13 studies (5 cohort studies and 8 randomized controlled trials) involving 7,846 patients were included, demonstrating that Edaravone-Dexborneol significantly improved 90-day mRS scores (0-1) compared with Edaravone alone (RD: 0.08, 95% CI: [0.03, 0.13], P = 0.001). When compared with standard treatment, NIHSS scores were significantly lower in the Edaravone-Dexborneol group (MD: -2.18, 95% CI: [-3.75, -0.62], P = 0.006), and no significant difference was observed in mRS (0-1) or the risk of symptomatic intracranial hemorrhage (sICH). Safety outcomes showed a possible dose-dependent adverse event (AE), including hyperhomocysteinemia and hypokalemia. Edaravone-Dexborneol might be an effective treatment for improving functional recovery in patients with AIS and appears to have a relatively favorable safety profile. However, careful dosing is necessary to minimize AEs. Future research should focus on large-scale trials, long-term outcomes, and mechanistic studies to optimize treatment protocols.

Methotrexate (MTX) remains the first-line pharmacotherapy for rheumatoid arthritis (RA), yet gastrointestinal (GI) adverse events (AEs) are frequently reported. This systematic review and meta-analysis aimed to estimate the prevalence of GI AEs among RA patients treated with MTX. A comprehensive search of PubMed, Scopus, and Cochrane databases was conducted, including observational and interventional studies reporting GI AEs in adult RA patients receiving MTX. Risk of bias was assessed using the Newcastle-Ottawa Scale, JBI Critical Appraisal Tool, and Cochrane RoB 2 as appropriate. Pooled prevalence estimates with 95% confidence intervals (CIs) were calculated using a random-effects model. Thirty-seven studies involving 19,986 participants were included. Nausea and abdominal pain were the most frequently reported AEs, with pooled prevalence of 24.3% (95% CI: 16.7-34.0) and 19.6% (95% CI: 13.9-26.9), respectively. Substantial heterogeneity was observed across studies and persisted after stratification by MTX route or study design. Nine studies reported discontinuation due to GI AEs, with rates ranging from 1.7% to 23.4% and a pooled prevalence of 8.5% (95% CI: 5.0-14.3). Gastrointestinal AEs affect approximately one-fifth of RA patients receiving MTX, with nausea and abdominal pain being the most common symptoms. GI events leading to treatment discontinuation were relatively uncommon. Clinician awareness and timely management of GI AEs are important to prevent nonadherence and optimize MTX therapy.

Machine learning (ML) applied to diffusion tensor imaging (DTI) has emerged as a promising tool for detecting microstructural brain alterations in movement disorders. However, existing studies vary widely in design, sample size, imaging pipelines, and analytic rigor, resulting in high methodological heterogeneity that limits quantitative comparability. This exploratory meta-analysis and narrative synthesis aimed to characterize performance trends, methodological diversity, and sources of variability among ML models trained on DTI data for classifying movement disorders, rather than to infer a single pooled diagnostic effect. This was designated exploratory because extreme heterogeneity prevented confirmatory pooled effect inference, so the analysis focused on describing performance distributions and methodological patterns rather than estimating a unified diagnostic effect. A systematic search of PubMed, Web of Science, and Scopus identified human studies applying ML algorithms to DTI for diagnostic or classification purposes. Accuracy, sensitivity, specificity, and the area under the curve (AUC) were extracted, with multiple imputation used for incomplete metrics with missingness rates below 40%. Random-effects modeling was employed to provide descriptive summaries, and subgroup analyses were conducted to explore trends across disorders, model architectures, and imaging modalities. Study qualities were assessed with JBI tools. Forty-six studies (2016-2024) were included, spanning Parkinson's disease, Tourette syndrome, and essential tremor. Reported performance was generally high (median AUC ≈ 0.91), but between-study heterogeneity was extreme (I2 = 94.7%), indicating that studies were estimating distinct effects. Disorder-specific subgroup AUCs varied markedly: Essential Tremor (0.95), Parkinson's (0.90), Tourette's (0.88), and Other (0.79). Deep learning and radiomics-based models have reported higher accuracies, but they were often trained on small, single-center cohorts (37-139 participants), which limits their external validity. Pooled statistics were presented descriptively to illustrate performance ranges despite high heterogeneity, and were not interpreted as confirmatory effect sizes. ML models using DTI demonstrate high internal performance across studies, although generalizability remains limited across multiple movement disorders; however, current evidence remains exploratory due to small sample sizes, methodological fragmentation, and a lack of standardized imaging pipelines. Rather than confirmatory inference, these findings provide a descriptive map of emerging trends in ML-DTI diagnostics. Future progress will depend on data harmonization initiatives, multicenter collaborations, and federated learning frameworks that can support reproducible, generalizable, and clinically interpretable models.

Numerous emerging systemic therapies, including monoclonal antibodies and Janus kinase (JAK) inhibitors, are effective for atopic dermatitis (AD). However, their effects on the incidence of airway comorbidities like asthma and allergic rhinitis in AD patients remain unclear. This network meta-analysis evaluates and compares the risks of these adverse events among patients with AD receiving different biologics and systemic JAK inhibitors. PubMed, Cochrane Library, Embase, and Web of Science were searched for randomized controlled trials (RCTs) evaluating asthma and allergic rhinitis in AD patients receiving JAK inhibitors or biologics, from inception to January 4, 2025. Data synthesis employed a Bayesian network meta-analysis with random-effects modeling, using relative risk (RR) and 95% credible intervals (CI) as effect measures. Meta-regression assessed the impact of study design and participant characteristics on intervention effectiveness. The surface under the cumulative ranking curve (SUCRA) ranked intervention safety profiles, and methodological quality was appraised via the Cochrane ROB 2.0 tool. A total of 26 randomized clinical trials (13,069 participants) met inclusion criteria, with 9530 receiving JAK inhibitors/biologics and 3540 assigned to placebo. Compared to nemolizumab 90 mg, dupilumab 300 mg (RR = 0.1, 95% CI: 0.01, 0.93) and tralokinumab 150 mg (RR = 0.03, 95% CI: 0, 0.77) were associated with a significantly lower risk of asthma. SUCRA analysis identified ISB 830 600 mg (SUCRA = 8.0%) as the highest for asthma-related adverse events and tralokinumab 150 mg (SUCRA = 95.1%) as the lowest. For allergic rhinitis, abrocitinib 100 mg had the highest adverse event incidence (SUCRA = 10.3%) and dupilumab 200 mg the lowest (SUCRA = 93.8%). Cluster analysis confirmed dupilumab 200 mg as associated with the lowest combined risk of both conditions, while abrocitinib 100 mg had the highest. Among patients with AD receiving biologics or JAK inhibitors, dupilumab was associated with the lowest risk of asthma and allergic rhinitis in our analysis. Owing to confounding between dose and patient factors (age, disease severity, etc.) in included trials, no specific dose recommendations can be made. These findings warrant confirmation by future large-scale RCTs stratified by age and dose. PROSPERO (CRD42024595904).

Short telomere length (TL) has been associated with chronic diseases and reduced lifespan. Vitamin D may help preserve telomeres through its anti-inflammatory effects; however, the relationship between serum 25-hydroxyvitamin D (25(OH)D) levels and TL remains inconclusive. This meta-analysis was conducted to evaluate the association between circulating 25(OH)D and leukocyte TL (LTL). A comprehensive literature search was performed across PubMed, Scopus, Google Scholar, ClinicalTrials.gov, and Cochrane Library to identify relevant studies published up to February 2025. Standardized β coefficients with 95% confidence intervals were applied as the effect size metric to evaluate the associations using a random effect model. A total of 21 studies comprising 185,191 participants were analyzed. The overall results demonstrated a positive association between serum 25(OH)D levels and LTL (β = 0.04, 95% CI = 0.02-0.06), with remarkable heterogeneity across studies (I²= 89.1%, P ≤.001). This association was supported in adults (β = 0.04, 95% CI = 0.03-0.06), women (β = 0.05, 95% CI = 0.01-0.08), individuals with vitamin D deficiency (β = 0.22, 95% CI = 0.01-0.43), and studies that adjusted for covariates (β = 0.05, 95% CI = 0.01-0.08). No significant associations were found in men, participants with serum 25(OH)D levels ≥ 30 ng/mL, children, or studies without covariate adjustments. The relationships were not influenced by the method of TL assessment, body mass index, smoking status, and sample size. Serum 25(OH)D levels showed a positive correlation with LTL in women, adults, and individuals with vitamin D deficiency.

Chronic hyponatremia is a common electrolyte disturbance associated with adverse outcomes. The optimal rate of correction remains uncertain, with current guidelines emphasizing avoidance of overcorrection. This systematic review and meta-analysis aimed to synthesize the existing evidence on patient and healthcare utilization outcomes associated with overcorrection in adults with chronic hyponatremia. This study followed a pre-registered protocol (PROSPERO CRD42024606516). Medline and EMBASE were searched from inception to May 2024. Eligible studies included original experimental or observational research. Included studies reported outcomes for adult patients with chronic hyponatremia who experienced overcorrection, and those who did not. The outcomes of interest were neurologic complications, acute care utilization (hospital and intensive care unit length of stay, re-admission) and mortality. Study quality was assessed using the Newcastle-Ottawa Quality Assessment Scale. Meta-analyses were performed using the Hartung-Knapp-Sidik-Jonkman random effects models when data allowed; otherwise, outcomes were synthesized narratively. Forty-three studies were included. Overcorrection of hyponatremia was associated with an increased odds of neurologic complications (OR 4.23, 95% CI 2.93 - 6.11, I2 = 0%) but lower odds of mortality (OR of 0.67, 95% CI 0.47 - 0.97, I2 = 82.3%). In sensitivity analyses restricted to studies at low risk of bias, the association between overcorrection and neurologic complications was no longer statistically significant (OR 3.22, 95% CI 0.40-25.83, I2 = 25.4%). Given the observational nature of included studies, indirect evidence, and high risk of bias across studies, the certainty of evidence is very low. While sodium overcorrection appears to be associated with increased risk of neurologic complications but lower risk of mortality, the limitations of the current literature warrant cautious application of these findings. Given the potential risks of under- and overcorrection, a reframing of practice to achieve adequate correction, rather than focusing on overcorrection avoidance alone may be warranted.

Chikungunya virus (CHIKV) poses a significant burden on affected populations, presenting substantial challenges to public health. This study aimed to assess the seroprevalence of the CHIKV in the Horn of Africa. We conducted a systematic review and meta-analysis by searching PubMed/MEDLINE, Scopus, Scientific Direct, Google Scholar, and reference lists for primary articles published from the inception of the database until November 30, 2023. The inclusion criteria covered seroprevalence studies of CHIKV in Ethiopia, Kenya, Somalia, South Sudan, Sudan, Eritrea, Uganda, and Djibouti. Pooled seroprevalence was estimated using a random effects model, and the meta-analysis was conducted with R Studio version 4.3.1 and the Metapro package. The study protocol adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and is registered in PROSPERO, CRD42023477057. From a pool of 87,567 potential studies, 34 eligible studies were included in our analysis. Most of the studies were conducted in Kenya (44%). Hospital-based studies were included in 59% of cases. A total of 23,400 participants were involved in the review. Of the 13,397 participants, 6778 (67.6% of those with information) were male. The pooled seroprevalence of CHIKV was 14% (95% CI: 9-23; I2 = 99%). Subgroup analysis was performed. The seroprevalence was higher in studies conducted in population settings: 15% (95% CI: 5-37; I2 = 99%) than in hospital settings. The seroprevalence of chikungunya was high from the 2004 to 2013 period, at 36% (95% CI: 13-68; I2 = 98%). Plaque reduction neutralization tests detected 15% (95% CI: 3-49%; I2 = 94%) of the chikungunya seroprevalence. The seroprevalence of CHIKV among inapparent infections was 17% (95% CI: 8-35; I2 = 98%). The meta-regression analysis revealed that the chikungunya seroprevalence was predicted by the countries of study, age group, and trends of infection over time. Our review highlights compelling evidence of CHIKV and other arbovirus circulation in the Horn of Africa, revealing diverse seroprevalence rates across different countries, age groups, laboratory tests, clinical manifestations, and time trends. The confirmatory gold standard, the plaque reduction neutralization test, increases diagnostic accuracy.

Platelet indices (PIs) - including platelet count (PC), plateletcrit (PCT), mean platelet volume, and platelet distribution width (PDW) - are routinely assessed in clinical practice. Although observational studies have reported associations between PIs and lung cancer outcomes, the dose-response relationship and causality remain unestablished. This study aims to determine prognostic thresholds of PIs and elucidate their causal roles in lung cancer. We systematically reviewed PubMed, Medline, and Web of Science (through December 2024) for studies on PIs and lung cancer prognosis. Hazard ratios (HRs) were pooled via random-effects models. Dose-response thresholds were identified using restricted cubic splines and generalized least squares. Two-sample Mendelian randomization (MR) analyses with inverse variance weighting assessed causality, complemented by sensitivity analyses (MR-Egger, weighted median). In the meta-analysis of 62 studies (N = 38,562 patients), elevated PC (HR = 1.016, 95% CI: 1.009 to 1.024) and PCT (HR = 1.704, 95% CI: 1.040-2.790) independently predicted poorer overall survival. A nonlinear dose-response relationship revealed that each 109/L increase in PC conferred a 4.2% higher risk of adverse prognosis in non-small cell lung cancer (HR = 1.042, 95% CI: 1.029 to 1.056), with a critical threshold at 177.5 × 109/mL. MR analyses demonstrated population-specific causality: a 1-SD increase in PC elevated lung cancer risk by 33% in East Asians (OR = 1.33, P < .001), while in Europeans, equivalent increments in PC and PCT increased small cell lung cancer (SCLC) risk by 17% (OR = 1.17, P = .01) and 19% (OR = 1.19, P < .001), respectively. Additionally, higher PDW was causally linked to a 6% increased lung cancer risk (OR = 1.06, P = .02). This first study integrating dose-response meta-analysis and MR evidence identifies PC and PCT as robust prognostic biomarkers for lung cancer, with population-specific causal effects. The identified PC threshold (177.5 × 109/mL) provides a clinically actionable tool for NSCLC risk stratification, highlighting the translational potential of routine PIs monitoring in oncology practice.

Dysregulated blood glucose levels and insulin resistance are key contributors to various metabolic complications and increased mortality. Among lifestyle interventions, dietary modification is a crucial strategy for improving glucose tolerance. Barley, rich in fiber and β-glucan, may offer a promising dietary approach for glycemic control. To evaluate the impact of barley intake on short- and long-term glycemic and insulin responses through a systematic review and meta-analysis. Through comprehensive searches in major scientific databases, 31 controlled trials with 34 intervention arms were identified, including a total of 660 case patients and 665 control participants. Two reviewers independently extracted data, and a random-effects model was used to calculate pooled estimates of outcomes. Barley supplementation significantly reduced postprandial glucose levels at 30 (-10.48 mg dL-1), 60 (-12.38 mg dL-1), and 120 (-6.95 mg dL-1) minutes; however, no significant effects were observed at 180 minutes. Barley supplementation significantly reduced postprandial insulin levels at 30 (-6.02 pmol L-1), 60 (-12.83 pmol L-1), and 180 (-5.89 mg dL-1) minutes; however, no significant effects were observed at 120 minutes. No significant changes in insulin levels were observed beyond the early postprandial period. In the long term, barley intake did not significantly affect fasting glucose or hemoglobin A1c levels. This meta-analysis supports the short-term benefits of barley consumption in improving early postprandial glucose and insulin responses. No significant impact was found on later or long-term glycemic markers. More high-quality trials are needed to confirm these outcomes. PROSPERO registration No. CRD42022368122.

Management of complete biliary obstruction remains challenging when conventional endoscopic or percutaneous approaches fail. Magnetic compression anastomosis (MCA) has emerged as a minimally invasive alternative; however, the evidence base is limited and methodologically heterogeneous. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of MCA in benign and malignant biliary obstruction. On August 27, 2025, we conducted a comprehensive search using PubMed, Scopus, Web of Science, and Cochrane Library for studies evaluating MCA in patients with biliary obstruction. The primary outcome was technical success (anastomosis creation), and secondary outcomes included recurrence rate, incidence of cholangitis, and time to anastomosis creation. Pooled single-arm estimates were calculated using a random-effects model. Of 772 articles screened, eight studies were included: 5 on benign biliary stricture (BBS) involving 102 patients, and three on malignant obstruction involving 82 patients. In the BBS group, technical success was 0.91 (95% CI: 0.84-0.95), the recurrence rate was 0.13 (95% CI: 0.034-0.38), and the incidence of cholangitis was 0.029 (95% CI: 0.01-0.087); the mean time to anastomosis creation was 9.89days. In the malignant obstruction group, technical success was 1.00, recurrence rate was 0.073 (95% CI: 0.033-0.15), and incidence of cholangitis was 0.073 (95% CI: 0.033-0.15). In this systematic review and meta-analysis, MCA appears to be a feasible and safe procedure, with high technical success rates and low recurrence and cholangitis rates across both groups. Larger comparative studies and randomized controlled trials are needed to confirm these findings.

To evaluate the effectiveness of cognitive interventions in enhancing the cognitive function of community-dwelling older adults living alone. Five databases were systematically searched for articles published until December 2024. The search identified three randomized controlled trials (RCTs) and four non-RCTs, including case - control studies and quasi-experimental studies, with sample sizes ranging from 20 to 78. After risk of bias was assessed, data were synthesized using a random-effects model. Interventions such as robotic assistance, reminiscence therapy, animal-assisted therapy, creative therapies, and multicomponent programs significantly improved cognitive function (mean difference [MD] = 2.85 in MMSE), reduced depression (standardized MD = -0.85), and mitigated loneliness (MD = -10.13 in UCLA-LS). High heterogeneity was observed, attributable to diverse protocols, participant characteristics, and study designs. Attrition and confounding biases were also identified. Cognitive interventions can improve cognitive and psychosocial outcomes in community-dwelling older adults living alone. However, further research is required to confirm these findings. Socially interactive cognitive interventions are a promising strategy for improving the cognitive and mental health of community-dwelling older adults living alone. Clinicians should implement these accessible interventions to improve the population's quality of life and support their independent living.

Background Copeptin, the C-terminal fragment of provasopressin, has emerged as a potential prognostic biomarker in sepsis. However, its predictive accuracy for mortality in adult patients with sepsis remains uncertain. We conducted a systematic review and meta-analysis to evaluate the diagnostic performance of elevated blood copeptin levels for mortality prediction in this population. Methods We systematically searched PubMed, Embase, Web of Science, Wanfang Data, and CNKI from inception to 22 May 2025, for observational studies assessing copeptin levels at admission or within 48 h in adults with sepsis. Pooled sensitivity, specificity, likelihood ratios, diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic curve (AUC) were calculated using a random-effects model. Study quality was assessed using QUADAS-2. Results Ten prospective studies involving 1,637 patients were included. Pooled sensitivity and specificity of elevated copeptin for predicting mortality were 0.77 (95% CI: 0.70–0.83; I 2 = 52%) and 0.76 (95% CI: 0.67–0.83; I 2 = 86%), respectively. The pooled positive and negative likelihood ratios were 3.16 (95% CI: 2.33–4.29) and 0.30 (95% CI: 0.23–0.40), with a DOR of 10.40 (95% CI: 6.62–16.33). The summary AUC was 0.83 (95% CI: 0.79–0.86), indicating good overall prognostic accuracy. Subgroup analysis according to the cutoffs of copeptin did not significantly affect the results. No significant publication bias was detected ( p = 0.58). Conclusion Elevated blood copeptin levels within 48 h of sepsis diagnosis show good prognostic accuracy for short-term mortality in adult patients with sepsis. These findings support the potential clinical utility of copeptin as a risk stratification tool in sepsis management. Systematic review registration https://www.crd.york.ac.uk/prospero/ , identifier CRD42024587540.

Bleeding and vascular complications are key safety concerns during transcatheter aortic valve implantation (TAVI). Protamine is routinely administered to reverse unfractionated heparin, yet its efficacy and safety profile remain debated, particularly regarding its influence on bleeding, vascular, and renal outcomes. A meta-analysis of published studies comparing protamine with placebo during TAVI was conducted. Primary outcomes included transfusion requirements, major and life-threatening bleeding, and major vascular complications. Secondary outcomes were acute kidney injury, cerebrovascular events, myocardial infarction, minor vascular complications, and 30-day mortality. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models, and heterogeneity was assessed with the I2 statistic. Protamine administration significantly reduced the need for blood transfusion (OR = 0.70; 95% CI 0.55-0.88; P = .00; I2 = 0%), major bleeding (OR = 0.54; 95% CI 0.31-0.92; P = .02; I2 = 42.6%), life-threatening bleeding (OR = 0.33; 95% CI 0.12-0.87; P = .03; I2 = 26.8%), and major vascular complications (OR = 0.44; 95% CI 0.28-0.67; P = .00; I2 = 0%). There were no significant differences in any bleeding (OR = 0.82; 95% CI 0.50-1.36; P = .45), acute kidney injury (OR = 0.81; 95% CI 0.61-1.07; P = .14), cerebrovascular events (OR = 0.82; 95% CI 0.43-1.59; P = .56), myocardial infarction (OR = 0.47; 95% CI 0.08-2.90; P = .42), minor vascular complications (OR = 0.76; 95% CI 0.51-1.15; P = .19), or 30-day mortality (OR = 1.12; 95% CI 0.68-1.85; P = .65). Heterogeneity was minimal across most analyses (I2 < 50%). Protamine reversal of heparin during TAVI appears safe and confers significant protective effects against transfusion requirements, bleeding, and major vascular complications, supporting its routine use in the absence of contraindications.

Type of the article: Research ArticleAI is widely regarded by the IMF and the World Bank as a catalyst for growth. AI should be understood as a multidimensional socio-technical system embedded across institutions, industries, and society. Its economic contribution depends on which pillars of the national AI system expand (e.g., R&amp;amp;amp;D capacity, infrastructure, governance, or social acceptance). For this reason, the seven pillars of AI development are measured by the AI Vibrancy subindices, which help avoid reliance on a single composite indicator that may conceal offsetting effects. This study examines how different pillars of the national AI ecosystem shape the architecture of the knowledge economy and its economic outcomes by estimating heterogeneous within-country associations between GDP per capita and seven AI ecosystem pillars, operationalized through AI Vibrancy subindices, using a balanced panel of 36 countries with complete data over the period 2020–2023. Fixed- and random-effects models are estimated using heteroskedasticity-robust and Driscoll-Kraay standard errors. The results indicate that, within countries over time, the R&amp;amp;amp;D (β = –5.676, p &amp;amp;lt; 0.001) and Infrastructure (β = –16.306, p &amp;amp;lt; 0.001) subindices have strong and statistically significant negative associations with GDP per capita, while Public Opinion shows an adverse effect that is significant at the 5% level under heteroskedasticity-robust inference (β = –9.126, p = 0.040) and marginally significant under Driscoll-Kraay inference (p = 0.054). Responsible AI exhibits a marginally positive association (β = 5.773, p = 0.065) in the Driscoll-Kraay specification, whereas Economy, Education, and Policy &amp;amp;amp; Government show no significant within-country effects.

Osteoarthritis (OA) is a frequent comorbidity in patients with type 2 diabetes mellitus (T2DM), significantly affecting health status and quality of life. Emerging evidence suggests metformin, a first-line agent for T2DM, may also have therapeutic effects on OA. This study aimed to evaluate the efficacy of metformin in improving symptoms and reducing the risk of joint replacement in patients with both OA and T2DM through a systematic review and meta-analysis. A comprehensive search was conducted across PubMed, Embase, Web of Science, the Cochrane Library, and China National Knowledge Infrastructure (CNKI) for studies published up to June 2025. Eligible studies included randomized controlled trials, cohort studies, and retrospective analyses examining metformin use in patients with OA and T2DM. Data on clinical outcomes-including the Visual Analogue Scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), total knee replacement (TKR), and total hip replacement (THR)-were extracted. Pooled effect sizes were calculated using random-effects models. Subgroup analyses were performed based on study design, metformin dosage, and treatment duration. Ten studies involving 243,221 participants were included. Metformin use significantly lowered TKR risk (HR = 0.46; 95% CI: 0.30-0.72) and improved pain scores (SMD = -2.04; 95% CI: -2.44 to -1.64). Subgroup analyses revealed that higher daily dosages (≥ 1.0g/d) and longer treatment durations (≥ 24months) were associated with greater reductions in joint replacement risk (HR = -0.95 and HR = -1.53, respectively). For symptomatic relief, randomized controlled trials (RCTs) consistently showed significant improvements across VAS pain (SMD = -1.90), WOMAC pain (SMD = -2.16), and functional scores (SMD = -1.49). Dose-escalation regimens (500-2000mg/d) and 12-week interventions generally yielded the most pronounced improvements in pain and stiffness. The pooled odds ratio for non-serious adverse events was 2.07 (95% CI: 1.19-3.60), indicating a higher frequency of mild side effects such as gastrointestinal distress; however, no serious metformin-related events were reported. Metformin use in patients with T2DM and OA is associated with significant reductions in pain and a decreased risk of TKR. Subgroup findings suggest that the benefits are dose- and duration-dependent, with RCT evidence strongly supporting symptomatic improvement. Further high-quality trials are warranted to define optimal dosing regimens. Key Points •Metformin therapy significantly alleviates joint pain and stiffness in patients with comorbid type 2 diabetes and osteoarthritis. •Metformin is associated with improved physical function, with randomized controlled trials showing consistent functional benefits. •Metformin use is associated with a significantly reduced risk of total knee replacement (TKR), while no statistically significantassociation is observed for total hip replacement (THR). •The protective association with joint replacement appears dose- and duration-dependent, with daily doses ≥ 1.0 g and treatmentdurations ≥ 24 months showing the greatest benefit.

Background and objective Desvenlafaxine (DVS), a commonly used serotonin-norepinephrine reuptake inhibitor (SNRI), is widely applied in the treatment of major depressive disorder (MDD). However, the efficacy and safety of different DVS dosages remain controversial. This study aims to systematically evaluate the efficacy and safety of various doses of DVS in treating MDD, providing evidence-based guidance for clinical dose selection. Methods A systematic search was conducted in PubMed, Embase, Web of Science, and the Cochrane Library to identify randomized controlled trials (RCTs) comparing different doses of DVS in adult MDD patients. A Bayesian random-effects model was employed for network meta-analysis, and surface under the cumulative ranking curve (SUCRA) was used to assess the overall performance of each dose in terms of efficacy (HAM-D17, CGI-S, MADRS scores) and safety (treatment-emergent adverse events, TEAEs). Publication bias was assessed using funnel plots. All data analyses were performed using R Studio and STATA. Results A total of eight RCTs were included. The analysis showed that DVS at 50, 100, 200, and 400 mg/day significantly outperformed placebo in improving HAM-D17, CGI-S, and MADRS scores, with the 200 mg/day dose showing numerically greater improvement than the other doses. Regarding safety, there were no statistically significant differences in adverse event rates between any DVS dose and placebo ( P &amp;gt; 0.05). According to the SUCRA rankings, DVS 200 mg/day tended to appear higher in the probabilistic ranking, although this reflects relative ordering rather than conclusive evidence of clinical superiority. Conclusion DVS at doses ≥ 50 mg/day significantly improves depressive symptoms compared with placebo. Among the evaluated doses, 200 mg/day consistently showed numerically greater improvements while maintaining acceptable tolerability; however, the certainty of dose differences remains limited, and no definitive “optimal” dose can be established based on the current evidence.

The emergence of Listeria monocytogenes pathogen threatens the era of antimicrobial drugs commonly used in treating listeriosis. This study reviewed the prevalence and antibiotic resistance profiles of L. monocytogenes in South Africa. The random-effect model meta-analysis was used to determine the pooled prevalence estimates (PPE) of L. monocytogenes isolates and their antibiotic resistance (AR) profiles from humans, food and the environmental samples. Original peer reviewed articles published from January 1 1990 to March 23 2024, were searched from PubMed, ScienceDirect, Google Scholar, Scopus, and African Journal Online databases. Comprehensive meta-analysis version 4.0 (CMA) software was used to calculate the PPE. A total of 2,931 samples (n = 1150 from humans, n = 1631 from food, and n = 150 from the environment) derived from 32 articles were incorporated into the meta-analysis. The overall PPE of L. monocytogenes was 73.3%, 33.5% and 44.5%, from human, food, and the environment samples, respectively. The L. monocytogenes serotype 4b-4d-4e had the highest PPE (19.5%). The AR profiles were screened from 1806 L. monocytogenes isolates with the overall multi-drug resistance PPE was 26.3%. The sulII resistance gene, which encodes a drug-resistant dihydropteroate synthase enzyme conferring resistance to sulfonamides, exhibited the highest prevalence of PPE at 47.3%. Among the isolates of L. monocytogenes from South Africa, the inlJ and inlB genes had high PPE values of 83.5% and 80.5%, respectively. These observations clearly demonstrate that L. monocytogenes is pathogen of "One Health" importance, which should not be under estimated. Therefore, a deliberate, concerted effort to formulate joint control and management of this bacteria is required from the human, animal, and environmental health sectors in South Africa.

Background Patients with depression have memory impairment. Exercise can improve memory in people with depression. This study employs a three-level meta-analysis to investigate the interventional effects of exercise on verbal and visual memory in patients with depression. Methods A systematic electronic search was conducted in China National Knowledge Infrastructure, Wanfang Data, China Biomedicine, PubMed, EMBASE, the Cochrane Library, and Web of Science to identify randomized controlled trials investigating the effects of exercise interventions on memory in individuals with depression, up to July 18, 2024. A three-level meta-analysis based on a random-effects model was performed using R. The risk of bias of the included studies was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool. Results A total of 16 studies were included in the analysis. The results indicated a statistically significant but small effect of exercise on verbal memory in patients with depression ( g = 0.17, 95% confidence interval (CI) [0.02–0.32], p = 0.03); however, the 95% prediction interval crossed zero, suggesting that the effect may not be consistent across different settings or future studies; however, the 95% prediction interval crossed zero, suggesting that the effect may not be consistent across different settings or future studies ( g = 0.27, 95% CI [−0.00–0.54], p = 0.05). Exercise intensity significantly moderated the effect of exercise on verbal memory in patients with depression ( F = 3.39, p = 0.04), whereas exercise type, session time, duration, age, and intervention content of the experimental group were not moderating factors ( p &gt; 0.05). Low-to-moderate intensity ( g = 0.43, p &lt; 0.01), duration ≤12 weeks ( g = 0.27, p &lt; 0.01), and session time ≤60 minutes ( g = 0.18, p = 0.03) of mind-body exercise ( g = 0.43, p &lt; 0.01) were most likely to improve verbal memory in patients with depression. The level of evidence was “moderate”. Conclusions Exercise may confer a small improvement in verbal memory among adults with depression, while no clear effect was observed for visual memory. However, further randomized controlled trials are needed to explore the impact of exercise on memory in patients with depression. Research plan was registered in international system evaluation platform PROSPERO ( https://www.crd.york.ac.uk/PROSPERO/ ) (CRD42023473393).

PurposeThis systematic review evaluates the efficacy and safety of different nasal adrenaline concentrations for bleeding control in endoscopic dacryocystorhinostomy (eDCR).MethodsFollowing PRISMA guidelines, we searched PubMed for studies reporting bleeding and cardiovascular events in adult eDCR. Outcomes were analysed using random-effects models. Statistical analyses employed random-effects models and I2 statistic. The protocol was registered with the Open Science Framework (OSF) (DOI: https://doi.org/10.17605/OSF.IO/EZDWG).ResultsAmong 103 screened articles, seven studies (comprising 856 patients) were included for meta-analysis. The 1:200,000 infiltrative adrenaline had significantly higher bleeding risk (15.3%, 95% CI: 11.1-20.5%) than 1:100,000 (3.8%, 95% CI: 2.0-6.5%) and 1:80,000 (2.0%, 95% CI: 0.7-4.3%), with an absolute risk difference of +13.3% (95% CI: + 9.8-16.8%, p < 0.0001) between 1:200,000 and 1:80,000. No significant difference existed between 1:100,000 and 1:80,000 (RD=+1.8%, 95% CI: -1.2-4.7%, p = 0.23). Each 100,000-fold dilution increased absolute bleeding risk by 12.1% (p < 0.001), with a number needed to treat (NNT) of 8 favouring 1:80,000 or 1:100,000 over 1:200,000.The most common infiltrative concentrations (n = 8,648) were 1:100,000 (57%), 1:200,000 (23%), and 1:80,000 (18%). For topical applications (n = 6,343), 1:1,000 (48%) and 1:100,000 (22%) predominated. While no particular topical concentration showed superior haemostasis (p > 0.05), 30-min 1:1,000 adrenaline application reduced bleeding vs. 5-min use (p < 0.05). Rare complications included ocular and cardiovascular events.Conclusions1:100,000 or 1:80,000 infiltrative adrenaline is preferred over 1:200,000 for lower bleeding risks, while topical adrenaline benefits from prolonged 30-min application. Surgeons should remain vigilant for rare systemic complications.

Background The study aimed to provide evidence to support optimal interventions for alleviating anxiety and depression symptoms in patients with polycystic ovarian syndrome (PCOS) through a systematic review and network meta-analysis. Methods A comprehensive literature search of PubMed, Embase, Cochrane Library, and Web of Science from their inceptions to January 2, 2025 was performed. The criteria for inclusion defined were as follows: (1) The study population consisted of female PCOS patients; (2) interventions included psychological therapy, exercise, drug treatment, or digital intervention; (3) studies that reported changes in anxiety and depression scores; and (4) randomized controlled trials (RCTs). Two reviewers independently screened the literature and extracted the data. Disagreements were resolved by consulting a third party. Standardized mean difference (SMD) was used for data recording in this study. The analysis of data was carried out based on a random-effects model, while network meta-analysis was implemented through R 4.4.0 and Just Another Gibbs Sampler (JAGS) 4.3.1. We conducted a Bayesian random-effects network meta-analysis (NMA) and ranked interventions using the surface under the cumulative ranking curve (SUCRA). Results This study included a total of 25 RCTs, involving 1,453 female PCOS patients, to evaluate the effects of various interventions in alleviating anxiety and depression symptoms. Effective interventions included emotion-focused therapy (EFT), peer support (PS), omega-3 plus vitamin E (O3+VE), and mindfulness stress management (MSM). Other interventions, such as metformin and vitamin D plus probiotics (VD+Pro), showed no significant benefit compared with control. Data on PS for anxiety were not analyzed in the present network meta-analysis because relevant trials could not be connected within the network structure. Conclusion Our study demonstrates that EFT and PS emerge as promising interventions in alleviating anxiety and depression symptoms in PCOS patients. Interventions such as O3+VE and MSM also showed potential in improving emotional states. Review registration: PROSPERO CRD420250655513.