Cardiovascular, kidney, and metabolic disorders are closely interconnected and jointly increase atherosclerotic burden and mortality risk. In 2023, the American Heart Association introduced the cardiovascular–kidney–metabolic (CKM) syndrome as a staged framework to characterize this multisystem risk. However, evidence linking CKM stages to mortality has not yet been quantitatively synthesized. We conducted a PROSPERO-registered (CRD420251161180) systematic review and meta-analysis following MOOSE and PRISMA guidelines. Four databases (PUBMED,Web of science, Embase, Cochrane library)were searched through August 8, 2025. Cohort studies assessing CKM stages (0–4) and reporting all-cause, cardiovascular disease (CVD), coronary heart disease (CHD), or stroke mortality were synthesized using random-effects models, with subgroup, meta-regression, and sensitivity analyses. 9 cohort studies including 10,330,498 participants were analyzed. Mortality risk increased significantly with advancing CKM stages. Compared with Stage 0, Stage 4 was associated with markedly higher risks of all-cause mortality (HR = 3.82, 95% CI: 2.24–6.52), CVD mortality (HR = 6.38, 95% CI: 5.22–7.80), CHD mortality (HR = 9.19, 95% CI: 6.93–12.20), and stroke mortality (HR = 5.48, 95% CI: 4.28–7.02). Meta-regression identified age and educational attainment as significant effect modifiers and sources of heterogeneity. In sex-stratified analyses, all-cause mortality was consistently higher in women across CKM stages, whereas CVD mortality was higher in women at earlier stages but higher in men at later stages. Leave-one-out (LOO) sensitivity analyses and publication bias assessments supported the robustness of these findings. Advancing CKM stages are associated with progressively higher mortality risks, highlighting their value for early risk assessment and targeted prevention.

Metabolic syndrome (MetS) confers a high risk of cardiovascular disease, type 2 diabetes, and premature mortality. Dyslipidemia, particularly abnormalities in pro-atherogenic lipid profiles, is a key pathophysiological feature. Although exercise is a cornerstone intervention for MetS, the optimal modalities and doses for improving pro-atherogenic lipid profiles remain unclear. This study compared the effects of different exercise interventions on pro-atherogenic lipid profiles in adults with MetS. We systematically searched PubMed, Embase, Web of Science, and the Cochrane Library through September 2025 for randomized controlled trials (RCTs) in adults with MetS. Pairwise meta-analyses, Bayesian network meta-analyses (NMAs), and dose-response models were performed. Risk of bias was assessed using RoB 2, and certainty of evidence was evaluated with the GRADE approach. Forty-nine RCTs involving 4144 participants were included, comprising 88 intervention arms: 28 high-intensity interval training (HIIT), 25 conventional aerobic exercise (CAE), 15 resistance training (RT), 14 combined aerobic and resistance exercise (CAREX), and 6 mind-body exercise (MBE). NMA showed that MBE ranked highest across most lipid outcomes, although its results were sensitive to a single trial. CAREX produced consistent and clinically meaningful reductions in non-high-density lipoprotein cholesterol (non-HDL-C), triglycerides (TG), and total cholesterol (TC), particularly at 500-1000 METs-min/week, while HIIT was most effective at 600-1000 METs-min/week. CAE and RT yielded overall favorable effects, but their dose-response thresholds were uncertain due to clustering of available trials around 600-900 METs-min/week. Low-density lipoprotein cholesterol (LDL-C) improved at≈244 METs-min/week (- 0.02 to - 0.28 mmol/L) and TG at≈510 METs-min/week(- 0.05 to - 0.10 mmol/L), with benefits plateauing above≈900 METs-min/week. Most outcomes were rated as moderate certainty using GRADE, with some downgraded for risk of bias and imprecision. Structured exercise may improve pro-atherogenic lipid profiles in MetS. CAREX and HIIT appear promising at moderate doses, while MBE could serve as a feasible low-impact alternative for individuals with reduced exercise tolerance. These findings suggest preliminary dose-based targets that may help guide personalized exercise prescriptions in clinical practice. PROSPERO CRD420251082352.

Background/Objectives: Impaired angiogenesis and vascular dysfunction are central features of chronic diseases such as cardiovascular disorders, neurodegeneration, and metabolic syndrome. Vascular endothelial growth factor (VEGF) plays a pivotal role in vascular repair and metabolic regulation, yet its responses to exercise remain inconsistently reported. This study aimed to systematically compare the effects of different exercise modalities and doses on VEGF levels across diverse populations. Methods: This review was registered in PROSPERO (CRD42025643709) and followed PRISMA guidelines. PubMed, Web of Science, Embase, and Cochrane Library were searched until 16 January 2025. Eligible studies were randomized or quasi-experimental trials reporting exercise-induced changes in serum/plasma VEGF. Data were extracted and assessed independently using JBI tools. Exercise types were categorized and doses standardized as metabolic equivalents (METs). Network meta-analysis was performed in Stata17.0 (SMD as effect size), with SUCRA used for ranking. Dose–response relationships were examined by meta-regression (remr package), and publication bias was assessed via funnel plots. Results: Twenty-eight studies (N = 1138) were included. In healthy adults, lower-limb resistance training produced the greatest VEGF increase, with benefits observed above ~600 METs-min/week and peaking near 1950 METs-min/week. Among obese individuals, combined aerobic and resistance training under hypoxic conditions showed the highest VEGF response, though dose-specific effects were not significant. In patients with chronic conditions, upper-limb resistance training within 756–950 METs-min/week was most effective, displaying a U-shaped dose–response relationship. No substantial publication bias was detected. Conclusions: The VEGF response to exercise appears to be influenced by both population characteristics and training dosage. High-intensity lower-limb resistance training may provide greater benefits for healthy adults, while obese individuals might experience enhanced responses with combined training under hypoxic conditions. For clinical populations, moderate-dose upper-limb resistance training may be particularly beneficial. Large-scale, long-term trials are needed to further clarify and refine exercise prescriptions targeting VEGF-mediated vascular adaptations.

This study aimed to compare the effectiveness of different exercise interventions in improving motor function recovery after stroke and to identify optimal rehabilitation strategies. A comprehensive search of five databases was conducted for randomized controlled trials (RCTs) up to March 13, 2025. Primary outcomes included the 6-min walk test (6MWT), 10-m walk test (10MWT), Berg Balance Scale (BBS), and FMA (total, UE, LE). Pairwise and Bayesian network meta-analyses were performed to compare the relative effects of different exercise modalities. Risk of bias was assessed using the RoB 2 tool, and evidence certainty was rated using CINeMA. This systematic review was prospectively registered in PROSPERO (CRD420251091242). A total of 317 RCTs involving 14,464 stroke patients were included. Network meta-analysis showed that, compared with routine care, electrical stimulation plus exercise (ESX) was associated with the largest improvement in walking endurance (MD = 53.4 m, 95% CI 14.27–92.58, p < 0.05, I² = 0%), while aerobic exercise (AE), functional training (FT), gait training (GT), and mind-body exercise (MBE) showed smaller effects. Lower limb training (LLT) demonstrated the greatest improvement in gait speed (MD = 0.18 m/s, 95% CI 0.14–0.23, p < 0.05, I² = 0%), with TCMEX, task-oriented training (TOT), and MBE also showing benefits. For balance (BBS), core stability training (CST) ranked highest (SMD = 0.77, 95% CI 0.30–1.24, p < 0.05, I² = 93.24%), followed by MBE and FT. FT showed the largest pooled effect for total FMA (SMD = 2.15, 95% CI 0.48–3.81, p < 0.05, I² = 93.86%), whereas MBE showed larger pooled effects for FMA-LE (SMD = 1.94, 95% CI 0.04–3.85, p < 0.05, I² = 97.54%) and FMA-UE (SMD = 1.85, 95% CI 1.08–2.63, p < 0.05, I² = 95.57%). Substantial heterogeneity was observed in several pooled comparisons. Meta-regression analyses identified multiple outcome-specific clinical and contextual factors (e.g., intervention duration, stroke phase, stroke severity, routine rehabilitation, age, sex distribution, and socioeconomic setting) that partially explained between-study variability, although no single factor accounted for heterogeneity across all outcomes. Importantly, global network diagnostics indicated acceptable overall model fit and consistency, supporting cautious interpretation of the comparative estimates at the network level. Several structured exercise interventions were associated with improved motor outcomes after stroke. High heterogeneity was observed in some comparisons; however, meta-regression analyses suggested several potential sources of variability, and global network assessments indicated generally acceptable heterogeneity. These findings should therefore be interpreted cautiously, particularly for outcomes with substantial between-study variation. This study received no specific funding.

Stroke is a leading cause of long-term disability worldwide, particularly among older adults, and severely compromises functional independence and quality of life. Exercise interventions are well established as effective strategies for promoting motor recovery through improvements in neuroplasticity, fitness, strength, and psychosocial well-being, yet most evidence to date has focused on immediate post-intervention outcomes. The durability of these benefits during follow-up periods—defined as the post-intervention phase when patients are observed after completing structured rehabilitation and begin transitioning to self-directed activities—remains poorly understood. Clarifying functional trajectories during this phase is critical for assessing the sustainability and real-world value of rehabilitation strategies. A systematic evaluation of motor function outcomes beyond formal intervention is therefore urgently needed to inform the design of programs that prioritize long-term recovery. This systematic review and network meta-analysis followed PRISMA 2020 guidelines and was registered in PROSPERO (CRD420251117014). Five databases (PubMed, Embase, Web of Science, Scopus, Cochrane Library) were searched up to March 13, 2025. We included randomized controlled trials comparing structured exercise interventions in post-stroke adults during follow-up periods, reporting motor function outcomes. Risk of bias was assessed using RoB 2.0, and evidence quality was graded via CINeMA. Pairwise and Bayesian network meta-analyses were conducted using netmeta and gemtc packages. Heterogeneity, inconsistency, regression, sensitivity, and publication bias analyses were also performed. Sixty-four trials (n = 3074) were included, covering 23 exercise modalities. For the 6-min walk test, resistance training demonstrated the greatest effect [mean difference (MD) = 21.79, 95% CI 8.19–35.40], followed by robot-assisted therapy (MD = 19.78, 95% CI 3.30–36.27). In the 10-m walk test, robot-assisted therapy ranked highest (MD = 0.06, 95% CI 0.01–0.12). Task-oriented training significantly improved balance [standardized mean difference (SMD) = 0.35, 95% CI 0.07–0.64]. No significant effects were observed in lower or upper limb Fugl-Meyer outcomes. Consistency and heterogeneity were generally acceptable, and no publication bias was detected. Resistance training and robot-assisted therapy appear most effective for enhancing walking capacity after stroke. Task-oriented training benefits postural balance. Evidence for upper and lower limb recovery remains inconclusive due to the small number of trials and wide confidence intervals. These findings can inform individualized, modality-specific rehabilitation strategies for older adults recovering from stroke. Registered on PROSPERO (CRD420251117014).

To compare the effects of different digitally and remotely deliveredexercise interventions on glycated hemoglobin (HbA1c) in adults with type 2diabetes mel