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PubMed2026

Comparative efficacy of LDL-C-lowering therapies in first-time vs. recurrent myocardial infarction prevention: a meta-analysis of large-scale randomized controlled trials.

AIMS: Reducing elevated low-density lipoprotein cholesterol (LDL-C) is central to global efforts to prevent myocardial infarction (MI). While many studies have evaluated LDL-C-lowering therapies in first-time and recurrent MI prevention, direct comparisons of their relative efficacy are lacking. Therefore, we conducted a systematic review and meta-analysis to compare the efficacy of LDL-C-lowering therapies in first-time vs. recurrent MI prevention. METHODS AND RESULTS: We searched three databases until 30 November 2024, for randomized controlled trials (RCTs) with at least 1000 patient-years of follow-up. Efficacy was quantified as relative risk (RR) with 95% confidence intervals (CIs). Differences in benefit magnitude were assessed using Cochran's Q test. Data were pooled with a random-effects model, and heterogeneity was measured using the I2 statistic. Additionally, we applied the Cochrane Risk of Bias Tool to evaluate study quality and utilized the GRADE method to assess the certainty of the evidence. This study included 22 large-scale RCTs involving 180 304 participants. In first-time MI prevention, LDL-C-lowering therapies achieved a remarkable 38% reduction in MI risk [12 RCTs; 79 604 participants; RR, 0.62 (95% CI, 0.55-0.69); P < 0.001]. In recurrent MI prevention, these therapies were associated with a more modest but significant 16% risk reduction [11 RCTs; 100 700 participants; RR, 0.84 (95% CI, 0.80-0.88); P < 0.001]. Importantly, the benefit magnitude between the two groups was significantly different (Q = 22.63; P < 0.001), highlighting the greater relative benefit in first-time MI prevention. Furthermore, the robustness of our findings was consistently supported by leave-one-out analyses, the absence of publication bias, high-quality GRADE evidence, and subgroup and sensitivity analyses. CONCLUSION: Our findings suggest that LDL-C-lowering therapies may offer a greater benefit in preventing first-time MI compared with recurrent MI.

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PubMed2026

Remotely Supervised, Home-Based Transcranial Direct Current Stimulation for Major Depressive Disorder: Systematic Review and Meta-Analysis.

BACKGROUND: Major depressive disorder affects over 280 million people worldwide, and access to effective treatment remains limited. Transcranial direct current stimulation (tDCS) is a noninvasive option, and portable devices now allow for home-based delivery under varying degrees of remote supervision. OBJECTIVE: This study aimed to systematically review and meta-analyze the efficacy, safety, feasibility, and acceptability of home-based and remotely supervised tDCS for depressive disorders. METHODS: Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 and PRISMA-S (Preferred Reporting Items for Systematic Reviews and Meta-Analyses literature search extension) guidelines, we searched MEDLINE, Embase, Web of Science, the Cochrane databases, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform up to July 2025, with backward and forward citation searching. Two reviewers independently screened records, extracted data, and assessed risk of bias (version 2 of the Cochrane risk-of-bias tool for randomized trials, Newcastle-Ottawa Scale for observational studies, and Critical Appraisal Skills Programme for qualitative studies) and certainty of evidence (Grading of Recommendations Assessment, Development, and Evaluation; GRADE). RESULTS: This review included 12 distinct studies (16 reports), of which 6 (50%) were randomized sham-controlled trials forming the meta-analytic pool. Active home-based tDCS produced a small, statistically significant improvement over sham (pooled Hedges g=0.36, 95% CI 0.06-0.66; P=.03; I2=34.3%). The effect was not robust to removal of the single largest positive trial (omitting the one study from 2025: g=0.39, 95% CI -0.12 to 0.91), and trial-level results were mixed: the 2 largest trials (one unsupervised [n=210] and one self-administered [n=141]) were negative on their primary depression outcomes, whereas the largest real-time supervised trial (n=174) was positive (between-group 95% CI 0.51-4.01; P=.01). This estimate was concordant in direction with an independent peer-reviewed meta-analysis of overlapping trials, which reported a pooled Montgomery-Åsberg Depression Rating Scale reduction (weighted mean difference -2.74, 95% CI -4.19 to -1.29) and Hamilton Depression Rating Scale reduction (weighted mean difference -2.24, 95% CI -4.16 to -1.49), attenuating to nonsignificance (P>.05) in major depressive disorder without comorbid cognitive impairment. The pooled effect fell at or near the minimal clinically important difference. GRADE certainty was moderate. Adverse events were predominantly mild: one pilot study was terminated early for skin lesions, and one nonfatal suicide attempt occurred in an unsupervised trial. CONCLUSIONS: Home-based and remotely supervised tDCS produces a small, statistically significant but clinically modest antidepressant effect that is sensitive to the inclusion of the largest positive trial, with the 2 largest trials being negative. The available controlled evidence does not establish supervision intensity as a determinant of efficacy. Current data are insufficient to recommend routine clinical adoption; adequately powered trials with standardized supervision and longer follow-up are needed.

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PubMed2026

Major cardiovascular event risk of advanced therapies in inflammatory bowel diseases: systematic review and meta-analysis.

BACKGROUND: Patients with chronic immune-mediated disorders (IMIDs), including inflammatory bowel disease (IBD), are at increased risk of cardiovascular disease. While advanced therapies show cardioprotective effects in other IMIDs, their impact on major adverse cardiovascular events (MACE) in IBD remains unclear. We conducted a meta-analysis of randomized controlled trials (RCTs) and observational studies evaluating MACE risk with advanced therapies in IBD. METHODS: Systematic search of PubMed, Embase, and Cochrane Central Register of Controlled Trials identified 43 studies (36 RCTs, including 9 long-term follow-up (LTF) studies, and 7 observational studies) published between 2002 and 2024. Primary analyses estimated odds ratios (OR) for MACE comparing advanced therapy to placebo, with secondary analyses stratifying studies by drug class and length of follow-up. Sensitivity analyses were conducted using alternative methods to account for zero-event data. RESULTS: Placebo-controlled RCTs showed a nonsignificant trend toward reduced MACE risk (OR 0.60; 95% CI 0.24-1.51), with similar findings across sensitivity analyses accounting for sparse and zero-event data. Class-specific trends suggested lower MACE risk with IL-12/IL-23 inhibitors (OR 0.35; 95% CI 0.05-2.21), JAK inhibitors (OR 0.57; 95% CI 0.16-2.06), and a potential increase with Anti-TNF agents (OR: 3.04; 95% CI 0.31-29.47), though none reached statistical significance. LTF studies showed consistent findings. Observational studies suggested lower MACE risk with Anti-TNF therapies (OR 0.29; 95% CI 0.21-0.40), but not with IL-12/IL-23 (OR 4.41; 95% CI 0.49-39.28) or JAK inhibitors (OR 1.57; 95% CI 0.86-2.84). CONCLUSION: Advanced therapies did not demonstrate a clear increase or decrease in cardiovascular risk in IBD. The discrepancies between RCTs and observational studies underscore the urgent need for rigorous-designed observational research with long-term follow-up to evaluate the real-world impact of advanced therapies on MACE risk.

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PubMed2026

Indications, Techniques and Complications Associated With Pterygoid Implants: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Pterygoid implants represent a graftless option for rehabilitation of patients with posterior maxillary atrophy, engaging the dense cortical bone of the pterygomaxillary complex. Despite clinical growth, a comprehensive synthesis of indications, surgical techniques, and complications is lacking. This review evaluated the prevalence of complications, implant survival rates, and marginal bone loss (MBL) associated with pterygoid implant placement. METHODS: The reporting of this review follows PRISMA 2020 guidelines. Six electronic databases (PubMed, Ovid, Scopus, WoS, CENTRAL, and Dentistry & Oral Sciences Source) were searched from 1 January 2020 to 31 December 2025. Included criteria comprised randomized and non-randomized clinical studies reporting outcomes of pterygoid implants (≥ 13 mm) in adult patients with posterior maxillary atrophy (minimum 10 implants). Risk of bias was assessed using JBI critical appraisal checklists. Proportions were pooled using the Freeman-Tukey double arcsine transformation under a random-effects model. Certainty of evidence was assessed using GRADE. RESULTS: Seventeen studies reporting 846 patients and 1915 pterygoid implants were included. The pooled survival rate was 97.9% (95% CI: 97.1%-98.6%; I2 = 0%; 14 studies) and the overall failure rate was 2.1% (95% CI: 1.4%-3.0%). Early failure rate was 0.9% (95% CI: 0.0%-3.0%; I2 = 59.5%). Late failure and MBL were summarized narratively. Certainty of evidence was low to very low. CONCLUSIONS: Pterygoid implants demonstrate excellent survival (97.9%) and low failure rates (2.1%), primarily early, supporting their reliability as a graftless solution for posterior maxillary atrophy. Complications appear infrequent though heterogeneously reported. Low evidence certainty necessitates prospective studies with standardized outcome reporting.

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PubMed2026

Effects of time-restricted eating on markers of glucose metabolism and regulation in individuals with prediabetes or type 2 diabetes: a systematic review and meta-analysis of randomised controlled trials.

AIMS/HYPOTHESIS: This systematic review and meta-analysis aimed to investigate the effects of time-restricted eating (TRE) on glucose metabolism and regulation in individuals with prediabetes (fasting blood glucose of 5.6-6.9 mmol/l or HbA1c of 39-47 mmol/mol [5.7-6.4%]) or type 2 diabetes (fasting blood glucose ≥7 mmol/l or HbA1c ≥48 mmol/mol [6.5%]). METHODS: A literature search was performed in MEDLINE, Embase and CENTRAL from inception to 5 August 2025. Moreover, forward and backward citation searches were performed. Eligible studies were RCTs in adults with prediabetes or type 2 diabetes, lasting ≥2 weeks, reporting markers of glucose metabolism and regulation, comparing TRE (≤12 h eating window) with a non-time-restricted control diet. Studies involving pregnancy, other fasting regimens, or non-peer-reviewed publications were excluded. Data were pooled as weighted mean differences with 95% CIs using random-effects generic inverse variance models in Cochrane Review Manager Web, and results are presented as forest plots. The certainty of evidence was defined using Grading of Recommendations, Assessment, Development and Evaluations methodology, and risk of bias was estimated by using the Revised Cochrane risk-of-bias tool for randomised trials (RoB 2). RESULTS: Out of 2043 records identified through the database search, as well as 1249 from forward and backward citation searches, ten RCTs including 599 participants were included. The mean length of the studies was 4 months, and the eating windows ranged from 4 to 10 h per day. The pooled meta-analysis showed no overall effect of TRE on HbA1c (-3.33 mmol/mol; 95% CI -6.87, 0.20 (-0.30% points; -0.63, 0.02); p=0.06, moderate certainty). Nevertheless, following stratification by subgroups, TRE resulted in a reduction in HbA1c of 0.93 mmol/mol (-1.70, -0.17 [-0.09% points; -0.16, -0.02]; p=0.02) in individuals with prediabetes but not in individuals with type 2 diabetes (-4.68 mmol/mol; -10.08, 0.72 (-0.43% points; -0.92, 0.07); p=0.09). TRE reduced fasting blood glucose in the pooled analysis (-0.30 mmol/l; -0.53, -0.07; p<0.01, moderate certainty) as well as in the subgroup analyses in individuals with prediabetes (-0.14 mmol/l; -0.27, -0.01; p=0.03) and with type 2 diabetes (-0.48 mmol/l; -0.78, -0.17; p<0.01). Moreover, TRE lowered body weight by 1.6 kg (-2.2, -1.0; p<0.001) in the pooled analysis. The evidence was limited by imprecision arising from wide confidence intervals in some of the included studies, which may be due to small sample sizes. Lastly, the effects of TRE on markers of insulin sensitivity, beta cell function and continuous glucose monitoring measurements were inconclusive. CONCLUSIONS/INTERPRETATION: Moderate-certainty evidence indicates that TRE reduces fasting blood glucose but not HbA1c. The subgroup analyses revealed that TRE improved HbA1c and fasting glucose in individuals with prediabetes and improved fasting glucose in individuals with type 2 diabetes. Future large-scale studies should investigate long-term effects of TRE in prevention and treatment of type 2 diabetes. TRIAL REGISTRATION: PROSPERO CRD42024523591 FUNDING: This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. Three authors (JS, A-DT, THA) are employed at Steno Diabetes Center Copenhagen, a public hospital and research institution under the Capital Region of Denmark, partly funded by a grant from the Novo Nordisk Foundation.

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PubMed2026

Effects of Moderate-Frequency Resistance Training on Cardiometabolic Risk Factors in Adults With Overweight or Obesity: A Systematic Review and Meta-Analysis.

BACKGROUND: Resistance training (RT) effectively manages cardiometabolic risk factors in adults, but the specific effects of moderate-frequency RT (2-3 sessions/week) in adults with overweight or obesity are understudied. OBJECTIVE: This study aimed to evaluate moderate-frequency RT's effects on cardiometabolic risk factors in this population and quantify effect sizes. DATA SOURCES: PubMed, Web of Science, EMBASE, and Cochrane Library searched up to July 2025. ELIGIBILITY: English randomized controlled trials (RCTs) comparing RT (≥ 7 weeks) to nonexercise control; nonathletic adults ≥ 18 years with BMI ≥ 25 kg/m2. PARTICIPANTS: 454 participants across 12 RCTs (mean age 58.93 ± 12.87 years; mean BMI 31.2 ± 3.5 kg/m2; ~50% female). RESULTS: RT significantly reduced diastolic blood pressure (MD = -1.53 mmHg; 95% CI: -2.16 to -0.91; p < 0.01), LDL-C (MD = -0.25 mmol/L; 95% CI: -0.41 to -0.08; p < 0.01), and triglycerides (MD = -0.17 mmol/L; 95% CI: -0.30 to -0.04; p = 0.01). No significant effects on systolic blood pressure, mean arterial pressure, waist circumference, glycemic markers, total cholesterol, or HDL-C. Subgroup analyses showed larger LDL-C/triglyceride improvements with concurrent dietary control. CONCLUSION: Moderate-frequency RT inconsistently improves cardiometabolic risk factors, benefiting diastolic blood pressure, LDL-C, and triglycerides but not glycemic or other parameters. Combining with dietary control may enhance benefits, supporting RT as a complementary strategy in multimodal lifestyle interventions. TRIAL REGISTRATION PROSPERO: CRD42022343167.

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PubMed2026

Comparative genomic and proteomic analysis reveals orthogroup structured evolution of tick protease inhibitors.

Protease inhibitors (PIs) play central roles in regulating endogenous proteolysis and host-parasite interactions in ticks. However, the evolutionary architecture underlying their diversification across tick lineages remains insufficiently resolved. Here, we performed a genome-wide comparative analysis of predicted proteomes from 14 tick species to systematically characterize PI repertoires. In total, 4931 putative PIs were identified and grouped into 20 families using the MEROPS classification system. Further, PI families such as Antistasin, WAP-type, and Pacifastin, which have not previously been systematically reported in tick genomes, were classified. Orthogroup inference demonstrated that PI expansion is structured at the level of evolutionary lineages rather than uniformly across families. By stratifying orthogroups according to duplication burden and taxonomic conservation, we identified a broadly conserved single-copy core under strong purifying selection. Motif level analysis of serpin reactive center loops further revealed conservation of inhibitory specificity within single copy orthogroups and diversification of key functional residues in duplication-associated lineages. Integration of secretion prediction and tissue-resolved proteomics from Hyalomma anatolicum and Rhipicephalus microplus demonstrated that evolutionary stratification is reflected at the protein level. Together, these findings provide an orthogroup-resolved evolutionary framework linking duplication dynamics, molecular evolution, and tissue-level protein deployment. This integrative approach offers a systematic basis for prioritizing conserved and diversified PI lineages for future functional and anti-tick intervention studies.

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PubMed2026

Compliance With Ecological Momentary Assessment Among Patients With Cancer: Systematic Review and Meta-Analysis.

BACKGROUND: Patients with cancer often experience substantial fluctuations in psychological states during disease management. Traditional research tools are limited in capturing these dynamic changes in real time, constraining clinicians' understanding of patients' true conditions. Ecological momentary assessment (EMA) enables high-frequency, real-time data collection, providing patient-reported data with greater ecological validity. However, the effectiveness of EMA studies critically depends on patient compliance, and reported compliance rates vary widely, with a lack of systematic quantitative synthesis. OBJECTIVE: This study aims to systematically review and quantitatively analyze compliance with EMA among patients with cancer, and to examine whether EMA design characteristics were associated with compliance. METHODS: Web of Science, PubMed, Embase, Cochrane Library, CINAHL, PsycINFO, CNKI, and Wanfang databases were searched for literature published up to April 30, 2026. Compliance was defined as completed prompts divided by delivered prompts. Single-group proportions were pooled using logit transformation and random-effects models with the Hartung-Knapp-Sidik-Jonkman adjustment. Prediction intervals were calculated to describe the expected distribution of compliance in future comparable settings. Subgroup analyses, univariable meta-regressions, leave-one-out sensitivity analyses, and tests for small-study effects were performed. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data, methodological reporting quality was assessed using a modified Checklist for Reporting EMA Studies, and certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: Twenty-three studies involving 13,565 participants were included. The pooled compliance rate was 78.55% (95% CI 73.48%-82.87%), with a prediction interval of 48.59%-93.41%. Subgroup analyses identified no robust differences across study characteristics. Although study length showed a statistically significant subgroup test, the result was not stable after excluding singleton categories. Meta-regression analyses similarly found no significant linear associations for study length, prompts per day, items per prompt, or assessment window. Leave-one-out analyses showed that no single study drove the pooled estimate. Regarding the risk of bias, 2 studies were judged as low, while 21 were judged as moderate risk. Quality scores ranged from 6.5 to 9.0, and the certainty of evidence for the pooled compliance rate was rated as very low according to the Grading of Recommendations Assessment, Development, and Evaluation approach. CONCLUSIONS: Overall compliance with EMA among patients with cancer was moderate to high, suggesting that repeated real-world assessment may be feasible in oncology research settings. Nevertheless, the very high heterogeneity, wide prediction interval, and very low certainty of evidence indicate that compliance is context-dependent. The pooled estimate should therefore be interpreted as an approximate benchmark rather than a universal expected rate. Future oncology EMA studies should use standardized compliance denominators, report missing prompts transparently, and prospectively evaluate patient-centered design strategies that reduce burden while preserving data quality.

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PubMed2026

Paediatric penile length: a systematic review and meta-analysis.

OBJECTIVE: To assess geographical variation in stretched penile length among prepubertal boys and evaluate temporal trends over the past two decades, as defining reference values for genital organ size remains crucial for early identification of development disorders. METHODS: The PubMed, Cochrane and Scopus databases (no deadlines for publishing were imposed) were searched according to the Preferred Reporting Items for Systematic Review and Meta-analyses statement. Five authors independently extracted individual participant data and assessed the risk of bias. Studies with quantitative penile lengths were included; those involving congenital malformations were excluded. The review protocol was prospectively registered in the International Prospective Register of Systematic Reviews (registration number CRD42022335643). RESULTS: A total of 55 studies from 2000 to 2024 were evaluated, including data from 31 915 boys. Pooled mean stretched penile length estimates were 3.07 cm (95% confidence interval [CI] 2.88-3.26 cm) for the 1-week-old boys, 3.73 cm (95% CI 3.53-3.93 cm) for the 1-year-old boys, 4.69 cm (95% CI 4.49-4.88 cm) for the 2-5 year-old boys, and 5.43 cm (95% CI 5.20-5.66 cm) for the 5-10 year- old boys. When comparing data from the 2000s to the 2020s, stretched penile length decreased by 16.2% (from 3.46 to 2.90 cm), 16.3% (from 4.17 to 3.49 cm), 21.5% (from 5.31 to 4.17) and 26.2% (from 6.46 to 4.77 cm) in the 1-week-old, 1-year-old, 2-5-year-old and 5-10-year-old boys, respectively. Subgroup analysis for those aged >2 years showed significant variations by geographical region (P < 0.001). CONCLUSIONS: The present study observed large variations in penile length across geographical regions and among prepubescent boys of different ages, while also suggesting a possible decline over the past two decades.

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PubMed2026

Effect of adding umbilical cord blood derived stem cells to haploidentical stem cell transplant (haplo-cord) on post-transplant survival and graft-versus-host disease in patients with hematological malignancies: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Haploidentical stem cell transplantation (haplo-SCT) carries a substantial risk of graft-versus-host disease (GvHD), whereas umbilical cord blood (UCB) transplantation offers lower GvHD risk but slower engraftment. The haplo-cord approach combines both graft sources, aiming to mitigate GvHD while ensuring timely engraftment. This meta-analysis compares haplo-cord transplantation with haplo-SCT alone for the treatment of hematological malignancies. METHODS: Four electronic databases and two clinical trial registries were systematically searched. Effect sizes from eligible studies were pooled using odds ratios (ORs) for dichotomous outcomes and hazard ratios (HRs) for time-to-event outcomes. RESULTS: Twelve studies met the inclusion criteria. Haplo-cord was associated with a statistically significant reduction in chronic GvHD (OR = 0.62, 95%-CI: 0.42-0.93), while no significant difference was observed for grade II-IV acute GvHD (OR = 0.75, 95%-CI: 0.52-1.09). Survival outcomes favored haplo-cord, with lower HRs for overall survival (HR = 0.68, 95%-CI: 0.53-0.86) and event-free survival (HR = 0.61, 95%-CI: 0.52-0.72), while non-relapse mortality was not significant. Relapse at 3 years was significantly lower with haplo-cord (OR = 0.54, 95%-CI: 0.35-0.82). Haplo-cord also demonstrated higher day-30 engraftment, along with lower relapse-related and GvHD-related mortality, while CMV and EBV viremia showed no difference between groups. CD34 selection in the haplo graft significantly influenced effect sizes and heterogeneity in both subgroup analyses and meta-regression for acute GvHD. CONCLUSION: Haplo-cord transplantation improves GvHD outcomes, survival, and relapse risk compared with haplo-SCT alone. However, whether protocol optimization, possibly via CD34 selection, confers additional benefit remains uncertain and requires confirmation in future studies.

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PubMed2026

Corticosteroids as adjunctive therapy to standard treatment in Kawasaki disease: a GRADE-assessed systematic review and meta-analysis of randomized controlled trials.

UNLABELLED: Kawasaki disease (KD) is an acute systemic vasculitis and the leading cause of acquired heart disease in children in developed countries. While IVIG plus aspirin remains standard treatment, 10-20% of patients are IVIG-resistant and face an elevated risk of coronary artery abnormalities. Corticosteroids have been explored as adjunctive therapy, though evidence on their benefit remains inconsistent. To assess the efficacy and safety of adjunctive corticosteroids in Kawasaki disease across key clinical outcomes. This PRISMA 2020-compliant systematic review and meta-analysis included RCTs identified through database searches up to April 2026. Risk of bias was assessed using Cochrane RoB 2.0. Data were pooled using random-effects models to estimate risk ratios (RRs) and mean differences (MDs) with 95% CIs. Subgroup analyses, leave-one-out sensitivity analyses, and GRADE certainty appraisal were also performed. Eight studies (n = 4106) were included. No significant differences were found in coronary artery abnormalities (CAA) within 1 month (RR 0.49, 95% CI 0.17-1.42), after 1 month (RR 0.81, 95% CI 0.43-1.55), fever duration (MD - 1.75, 95% CI - 3.71 to 0.21), or adverse events (RR 1.08, 95% CI 0.57-2.07). Hospital stay was modestly shorter with corticosteroids (MD - 0.99, 95% CI - 1.86 to - 0.11). Exploratory subgroup analyses suggested potential benefits with prednisolone-based and prolonged corticosteroid regimens for selected outcomes; however, these findings should be interpreted cautiously given multiple subgroup comparisons. Overall certainty of evidence was very low. CONCLUSION:  Adjunctive corticosteroids did not significantly improve major outcomes in KD. Prednisolone-based regimens showed some promise, but high-quality trials are still needed before any firm conclusions can be drawn. WHAT IS KNOWN: • Corticosteroids have been studied as adjunctive therapy for Kawasaki disease, but their effects on coronary outcomes and other clinical outcomes remain inconsistent. WHAT IS NEW: • This meta-analysis found no significant improvement in major outcomes with adjunctive corticosteroids, although prednisolone-based and prolonged regimens may provide benefits for selected outcomes.

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PubMed2026

Efficacy of NAs in combination with Peg-IFN for functional cure in patients with CHB: a meta-analysis of RCTs.

BACKGROUND: The goal of treating chronic hepatitis B (CHB) is to achieve functional cure. We aimed to evaluate the efficacy of the combination of nucleoside (acid) analogues (NAs) and pegylated interferon (Peg-IFN) on the functional cure of CHB patients at the EOT and at the EOF. METHOD: PubMed, Embase, and Web of Science were searched systematically up to March 15, 2025. Sixteen RCTs on CHB patients receiving combination or monotherapy were included. RESULT: Compared with NAs treatment, the NAs combined with Peg-IFN treatment group significantly improved HBsAg clearance rate (RR: 14.05, 95% CI 6.13-32.20) and HBsAg seroconversion rate (RR: 12.82, 95% CI 5.08-32.33) at the EOT. Moreover, compared with NAs treatment, the NAs combined with Peg-IFN treatment group significantly improved HBsAg clearance rate (RR: 7.70, 95% CI 4.24-13.98), HBsAg seroconversion rate (RR: 11.93, 95% CI 5.14-27.67) at the EOF. However, compared with Peg-IFN monotherapy, the combination therapy group did not show any improvement in HBsAg clearance rate, HBsAg seroconversion rate, and the rate of qHBsAg decrease > 1 log10 IU/mL at the EOT and the EOF. Moreover, in terms of safety, the Peg-IFN monotherapy group showed more ALT flares (ALT > 5 × ULN) during the treatment process. CONCLUSION: Compared with NAs therapy, Peg-IFN combined with NAs therapy significantly improves functional cure rate. However, combination therapy shows no additional advantage over Peg-IFN monotherapy in achieving functional cure. The Peg-IFN monotherapy group has a higher incidence of ALT flares than the combination therapy group.

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PubMed2026

Proteomic analysis of cisplatin-induced spermatogenesis defects in mice.

BACKGROUND: Cisplatin is a crucial chemotherapeutic agent used for treating various cancers; however, its excessive use can cause irreversible damage to the reproductive system, and the protein expression profile of cisplatin-induced testicular injury remains unclear. METHODS: Male C57BL/6 mice were treated with cisplatin at various doses, and testes were collected for histological, immunofluorescence, and proteomic analyses. Germ cell loss and apoptosis were assessed using H&E staining, TUNEL assays, and immunofluorescence for LIN28A, SYCP3, MVH, and CDK1. Label-free quantitative proteomics identified differentially expressed proteins, which were analyzed for functional enrichment and protein-protein interactions. RESULTS: We observed that cisplatin treatment led to smaller testes, reduced sperm count, and a significant decrease in the number of spermatocytes and spermatids in mice. Label-free quantitative proteomic analysis revealed that cisplatin significantly reduced the expression of cyclin-dependent kinase 1 (CDK1), a key spermatogenesis regulator, in the testes. Reduction in CDK1 expression is correlated with spermatogenic arrest, particularly in spermatocytes. CONCLUSION: These findings highlight the critical role of CDK1 in cisplatin-induced spermatogenic dysfunction and provide new insights into fertility preservation strategies for patients with cancer undergoing chemotherapy.

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PubMed2026

Comparative efficacy and safety of bi-flanged metal stents versus lumen-apposing metal stents for endoscopic drainage of pancreatic fluid collections: a systematic review and meta-analysis.

INTRODUCTION: Pancreatic fluid collections (PFCs), particularly walled-off necrosis, are common complications of acute pancreatitis that often require endoscopic drainage. Bi-flanged metal stents (BFMS; NAGI; Taewoong Medical, Gyenoggi-do, Korea) and electrocautery-enhanced lumen-apposing metal stents (LAMS; AXIOS, Boston Scientific Corporation, Marlborough, Massachusetts, USA) are frequently used, but comparative data remain limited. This study aims to compare the efficacy and safety of BFMS and LAMS in the endoscopic drainage of PFCs. METHODS: This meta-analysis followed the Cochrane Handbook for Systematic Reviews of Interventions and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Comprehensive database searches were conducted through November 2024 to identify studies comparing BFMS and LAMS for endoscopic ultrasound-guided drainage of PFCs. Outcomes were pooled using a random-effects model with RevMan Web, and statistical significance was defined as a P value less than 0.05. RESULTS: Three studies ( n  = 627; 329 BFMS and 298 LAMS) met inclusion criteria. No significant differences were observed between BFMS and LAMS for technical success [odds ratio (OR): 1.16; 95% confidence interval (CI): 0.55-2.43] or clinical success (OR: 0.97; 95% CI: 0.51-1.87). Similarly, there were no differences in walled-off necrosis recurrence (OR: 2.01; 95% CI: 0.17-24.02), number of direct endoscopic necrosectomy sessions (OR: 0.52; 95% CI: 0.05-5.12), or mean number of endoscopic procedures (mean difference: 0.18, 95% CI: 2.08-2.45). Adverse events were also comparable between groups, including bleeding (OR: 0.64), infection (OR: 1.18), stent migration (OR: 1.83), and stent occlusion/dysfunction (OR: 1.71). CONCLUSION: BFMS and LAMS provide equivalent efficacy and safety in the endoscopic ultrasound-guided drainage of PFCs. Either stent type represents a viable therapeutic option. Further large-scale prospective studies are warranted to refine stent selection strategies.

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PubMed2026

Comparison of the predictive performance of systemic immune-inflammation index and neutrophil-to-lymphocyte ratio for three-month poor functional outcome in ischemic stroke: a systematic review and meta-analysis.

INTRODUCTION: Ischemic stroke (IS) is a leading cause of global mortality and disability. Early and accurate prognosis is crucial for patient management. The neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) are emerging inflammatory biomarkers; however, their relative predictive value for three-month poor functional outcome (modified Rankin Scale [mRS] > 2) remains uncertain. METHODS: We systematically searched PubMed, Embase, Web of Science, and the Cochrane Library up to 20 July 2025, adhering to PRISMA guidelines. Observational studies reporting the association of SII or NLR with three-month poor outcome were included. Study quality was evaluated using the Newcastle-Ottawa Scale. Area under the curve (AUC), odds ratios (OR), and standardized mean differences (SMD) were pooled using random-effects models in Stata 16.0. RESULTS: Twenty-one studies involving 7520 IS patients were analysed. NLR demonstrated marginally superior discriminative ability compared to SII (AUC 0.71, 95% CI: 0.67-0.76 vs. 0.68, 95% CI: 0.64-0.71), though this difference was not statistically significant. Elevated NLR was significantly associated with poor outcome (OR = 1.26, 95% CI: 1.17-1.37, p < .001), whereas SII was not (OR = 1.00, 95% CI: 1.00-1.00, p = .384). Both markers showed moderate effect sizes (SMD: NLR = 0.69, SII = 0.72; p < .001). NLR performed better in non-intervention and Chinese subgroups, while SII exhibited consistent AUC values across treatment and ethnic subgroups. CONCLUSION: NLR and SII are accessible prognostic markers in IS. NLR demonstrates superior accuracy and a significant association with poor outcome, while SII shows greater stability across patient subgroups. Both may assist in risk stratification, in resource-limited settings.

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PubMed2026

Efficacy and safety of cannabinoid-based interventions for behavioral and cognitive symptoms in dementia: systematic review and meta-analysis.

BACKGROUND: Behavioral and cognitive symptoms are frequent in Alzheimer's disease and dementia, and available pharmacological options offer limited benefit. Cannabinoid-based therapies have been proposed as alternatives, but evidence remains inconclusive. METHODS: We systematically searched PubMed, Embase, Web of Science, and the Cochrane Library through November 2025 for randomized controlled trials evaluating cannabinoids in Alzheimer's disease or dementia. Primary outcomes were agitation measured by the Cohen-Mansfield Agitation Inventory (CMAI) and neuropsychiatric symptoms assessed by the Neuropsychiatric Inventory-Nursing Home version (NPI-NH). Secondary outcomes included cognition using the Mini-Mental State Examination (MMSE) and adverse events. Standardized Mean Differences (SMDs) and Risk Ratios (RRs) were synthesized using random-effects (REML) and Bayesian random-effects models. Risk of bias was evaluated with RoB 2, and certainty of evidence with GRADE. RESULTS: Nine trials (334 participants) met inclusion criteria. Cannabinoids did not improve CMAI (SMD -0.58, 95% CI -1.71 to 0.55; I2 = 84%), NPI-NH total (SMD -0.02, 95% CI -1.00 to 0.96; I2 = 67%), NPI-NH agitation (SMD -0.44, 95% CI -1.45 to 0.57; I2 = 48%), or MMSE (SMD 0.86, 95% CI -16.33 to 18.06; I2 = 96%). Bayesian posterior estimates were close to zero, supporting the absence of effect. Leave-one-out analyses reduced heterogeneity only after excluding influential trials but did not alter results. Certainty of evidence was moderate for behavioral outcomes and low for cognition. Overall adverse events were similar to placebo, while somnolence was more frequent with cannabinoids (RR 2.03, 95% CI 1.29-3.20). CONCLUSIONS: Cannabinoid-based therapies do not improve agitation, neuropsychiatric symptoms, or cognition in Alzheimer's disease and increase somnolence.

Humans↗

PubMed2026

Effects of rumen fluid transplantation on longissimus dorsi muscle development in Xizang sheep: An association analysis based on transcriptomic and serum metabolomic profiles.

This study aimed to investigate the effects of rumen fluid transplantation (RFT) on the growth and development of the longissimus dorsi muscle in female Xizang sheep. After RFT, muscle lightness differed significantly between the two groups, with the LDC group showing significantly higher lightness than the LDT group. In contrast, no significant differences were observed between groups in other muscle phenotypic traits, including drip loss, pH, cooking loss, shear force, redness, and yellowness. Antioxidant-related indices (SOD, GSH-PX, MDA, CAT, and T-AOC) also showed no significant differences between groups. Histological analysis revealed that muscle fiber length, width, and density were significantly greater in the experimental group than in the control group. Transcriptomic analysis identified 515 differentially expressed genes (DEGs), of which 419 were downregulated. KEGG analysis indicated that genes involved in muscle development-related pathways, such as cell adhesion and the PI3K-Akt signaling pathway, were predominantly downregulated. Key serum metabolites (L-kynurenine, IPA, allantoin, and propionylcarnitine) showed highly significant positive correlations with muscle fiber growth indices. In contrast, metabolites such as l-carnitine, acetylcarnitine, and citrulline were negatively correlated with muscle fiber growth, but positively correlated with the expression of muscle structure-related genes (COL11A1 and EFNA5) and with meat lightness. Overall, this study provides new insights into the potential molecular basis by which RFT influences muscle growth and development. However, the mechanisms by which RFT affects muscle development and meat quality-related traits remain unclear and warrant further investigation.

Animals↗

PubMed2026

Genetic Diversity Analysis of Red Fox Populations (Vulpes vulpes L., 1758) in Natural and Anthropogenic Isolation.

This study presents a comparative analysis of the genetic structure and diversity of three red fox (Vulpes vulpes L.) populations representing different microevolutionary scenarios: panmixia (free-ranging Belarusian foxes), geographic isolation (free-ranging Scottish foxes), and anthropogenic selection (farm-bred foxes). Using a validated set of STR markers, multivariate statistical analysis was conducted to assess the genetic structure and the degree of genetic erosion across the studied groups. The wild red fox population in Belarus has been shown to maintain a state close to panmixia (PHWE = 0.090), characterized by a high effective population size (Ne = 694) and high allelic diversity. The island population from Scotland exhibits moderate gene pool depletion (Ne = 75.9) and a pronounced heterozygote deficiency (FIS = 0.18). Critical genetic erosion, which was characterized by a minimal effective population size (Ne = 60.2) and allelic fixation, was detected in the farm-bred group. The genetic distance between farm-bred and wild foxes (FST = 0.279; p = 0.001) reflects both the phylogeographic divergence between the Nearctic ancestors of farmed lineages and Palearctic wild populations, and the consequences of prolonged anthropogenic isolation, genetic drift, and selective breeding. These data indicate that artificial isolation and the impacts of genetic drift and targeted selection lead to a substantial depletion of the species' adaptive potential.

Animals↗