Background Instant messaging delivered through social platforms is increasingly used to support diabetes self-management. However, evidence remains difficult to interpret because trials vary widely in platform choice, intervention design, outcome constructs, and measurement instruments. Objective To synthesize the effects of instant-messaging interventions for diabetes across pre-specified outcome domains, and to explore whether platform type, follow-up duration, and study size help explain variation in effect estimates. Methods We searched seven databases (2010–2025) for randomized controlled trials in which diabetes interventions were primarily delivered via instant-messaging/social platforms. Outcomes were organized a priori into six domains: health behaviors, diabetes knowledge, attitudes/self-efficacy, glycemic outcomes, other clinical outcomes, and diabetes-related complications. Continuous outcomes were pooled as standardized mean differences (SMDs) and binary outcomes as risk ratios (RRs) using random-effects models (REML). To improve interpretability, we prioritized domain-level synthesis and performed platform-stratified pooling only when at least three effect sizes were available within a given domain. Heterogeneity was summarized using τ 2 and I 2 . Robustness was assessed using leave-one-out analyses; small-study effects were evaluated using funnel plots and Egger's test when ≥10 studies contributed to an analysis. Exploratory meta-regression examined follow-up duration and ln(sample size). Results Twenty-three trials contributed 236 effect estimates. Overall pooled effects across all continuous and binary outcomes were close to null and statistically non-significant, with substantial heterogeneity. Domain-specific synthesis showed clearer patterns: diabetes knowledge demonstrated the largest pooled improvement (SMD = 1.065, 95% CI 0.185–1.944), glycemic outcomes improved on continuous measures (SMD = −0.519, 95% CI −0.719 to −0.319), and behavioral outcomes showed a small but significant benefit (SMD = 0.359, 95% CI 0.010–0.709). Attitudes/self-efficacy and other clinical outcomes were more heterogeneous and did not show clear pooled benefits. For complications (binary outcomes), the pooled estimate suggested a potential reduction in risk (RR = 0.67, 95% CI 0.44–1.00) based on three studies and should be interpreted cautiously. Platform-overview pooling of continuous outcomes suggested variability across platforms, with more consistently positive pooled effects for Facebook Messenger-based interventions than for WhatsApp or WeChat; however, platform-by-domain pooling was often not estimable because many platform–domain combinations contributed fewer than three effect sizes. Meta-regression did not identify a clear linear association of follow-up duration or ln(sample size) with effect size, and explained little heterogeneity. Conclusions Instant-messaging interventions for diabetes do not yield a clearly favorable overall pooled effect, but they show credible benefits for behavioral outcomes and selected clinical endpoints. Variation in effects appears more consistent with differences in intervention design and implementation than with platform labels alone. Future trials should report intervention components and maintenance strategies in greater detail and evaluate interactive, care-integrated messaging models. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420251079157 , identifier: CRD420251079157.

Hyperglycemia and glycemic variability (GV) are predictors of adverse outcomes in critically ill patients; however, their roles in pulmonary embolism (PE) remain unclear. This study investigated the association between the mean blood glucose (MBG), GV, and mortality in patients with PE. A retrospective cohort study of patients with PE was conducted using the MIMIC-IV 3.0. GV was quantified using the coefficient of variation (CV). Patients were stratified according to tertiles of MBG and CV. Multivariable logistic regression, restricted cubic splines (RCS), and ROC curves were used to evaluate the associations with ICU and in-hospital mortality, supplemented by the threshold effect, sensitivity, and subgroup analyses. Among the 1,493 PE patients, the ICU and in-hospital mortality rates were 12.99% and 20.90%, respectively. A higher MBG or CV was significantly associated with an increased risk of ICU mortality and in-hospital mortality. RCS revealed a linear association between MBG and mortality, whereas CV exhibited an inverted U-shaped relationship with inflection points at 38.523% (ICU) and 37.038% (in-hospital). For every 1% increase in CV to the left of the inflection point, the relative risks of ICU and in-hospital mortality increased by 0.035. The combined model (MBG + CV + ERS (European Respiratory Society)) achieved AUCs of 0.735 (ICU) and 0.693 (in-hospital) for mortality prediction. MBG and CV are independent predictors of mortality in critically ill patients with PE, suggesting that optimal glycemic control may benefit this population.

Stroke is a major public health concern and a leading cause of disability and death in aging populations. Intrinsic capacity (IC), a concept introduced by the World Health Organization, reflects anindividual'soverall functional ability across multiple domains including cognition, psychological well-being, mobility, vitality, and sensory function. IC has emerged as a core metric within the healthy aging framework, but its prospective relationship with stroke risk remains unclear. A deeper understanding of this link may inform early, function-based prevention strategies. This study used data from 10,751 participants aged 45 years or older from the China Health and Retirement Longitudinal Study (CHARLS). Cox proportional hazards models were used to estimate the association between IC and incident stroke, with stepwise adjustment for demographic, behavioral, and health-related covariates. Modeling IC as a continuous variable enabled examination of linear trends, while quartile-based classification allowed evaluation of potential non-linear associations and improved interpretability. Kaplan-Meier curves and log-rank tests were used to compare stroke-free survival across IC quartiles. Restricted cubic spline analysis was performed to explore the presence of a non-linear association between IC and stroke risk. Robustness was tested through sensitivity analyses excluding participants with baseline cognitive impairment and those aged ≥80 years. Statistical analyses were conducted using Stata and R. Over a 7-year follow-up, 243 participants (2.26%) experienced incident stroke. Stroke incidence decreased progressively with increasing IC levels, from 4.84% in the lowest quartile to 0.46% in the highest. Kaplan-Meier analysis showed significantly lower cumulative stroke incidence among individuals with higher IC (log-rank p < 0.001). In fully adjusted Cox models, each one-point increase in IC was associated with a 35.1% reduction in stroke risk (HR = 0.649; 95% CI: 0.599-0.702). Compared to the lowest IC quartile, the highest quartile had an 89.6% lower stroke risk (HR = 0.104; 95% CI: 0.055-0.197). Restricted cubic spline models confirmed a predominantly linear inverse association, with a steeper risk gradient at lower IC levels. Subgroup analyses revealed stronger protective associations in women, older adults (≥60 years), urban residents, and non-smokers or non-drinkers. Results remained consistent across all sensitivity analyses. Higher IC was independently associated with a significantly reduced risk of incident stroke, underscoring IC's potential as a holistic, function-based indicator of cerebrovascular vulnerability. These findings provide empirical support for the World HealthOrganization'shealthy aging framework, emphasizing IC as a modifiable reserve that reflects early, multidomain functional decline before clinical disease onset. Incorporating IC into routine screening and prevention strategies may enhance early identification of high-risk individuals and enable more targeted, function-oriented interventions, thereby promoting healthy aging and helping to reduce the future burden of stroke.

Planetary health diet benefits brain health by decelerating biological aging.

Association between monocyte to high-density lipoprotein cholesterol ratio and stroke prevalence in American adults: A cross-sectional NHANES Study.

Metabolic Syndrome Severity and Stroke Risk: A Longitudinal Analysis in Middle-Aged and Older Chinese Adults.

Association of oral contraceptive use with mortality: Findings from NHANES.

Associations between methylglyoxal and cerebral small vessel disease and cognitive function - The Maastricht Study.

Schoolchildren's exposure to potentially toxic metals/metalloids and cognitive impairments in communities of the Brazilian Amazon new agricultural frontiers.

While emerging evidence suggests guideline-defined nonhypertensive blood pressure (BP) may encompass heterogeneous risk, the relationship between BP variations within nonhypertensive ranges and mortality risk remains inadequately characterized among individuals without traditional cardiovascular risk factors. This study investigated whether nonhypertensive range of SBP, DBP, and pulse pressure (PP) are associated with long-term mortality in a healthy population. This study included 80 730 UK Biobank participants without traditional cardiovascular risk factors and with nonhypertensive BP (SBP <140 mmHg, DBP <90 mmHg, and PP <60 mmHg). Participants were followed up for all-cause, cardiovascular, and noncardiovascular mortality. Associations were assessed using multivariable Cox proportional hazards models with restricted cubic splines. Over a median follow-up of 13.7 years, 2553 deaths occurred. SBP and PP showed significant nonlinear associations with all-cause mortality ( P -overall <0.01), while DBP showed a linear inverse association ( P -overall = 0.049). Compared to the third quintile, the lowest PP quintile (<40 mmHg) was associated with 26% higher mortality risk (hazard ratio 1.26, 95% confidence interval [95% CI] 1.10-1.44), and the highest quintile (53-60 mmHg) with 14% higher risk (hazard ratio 1.14, 95% CI 1.01-1.28). The lowest SBP quintile (<114 mmHg) was associated with 16% higher risk (hazard ratio 1.16, 95% CI 1.02-1.32) compared to the third quintile (120-126 mmHg). Even within nonhypertensive ranges, the lowest and highest quintiles of PP level, as well as low-normal SBP and DBP levels, were associated with increased mortality risk in a healthy population.

Prenatal exposure to long-chain, short-chain and emerging PFASs and cognitive development in young children: Evidence from the Wuxi Birth Cohort.

Sex-specific associations between depressive symptoms and cardiovascular risk among middle-aged and older adults without standard modifiable risk factors: Evaluating the 'SMuRF-less but depressed'.

Interferon-γ (IFNγ), a double-edge sword that affects prognoses in critically ill patients: A prospective study.

Incident cardiovascular diseases and changes in the ratio of serum creatinine to cystatin C: the sarcopenia index.

Agility, characterized by rapid whole-body movement in response to external stimuli, is a key performance determinant in team sports owing to its reliance on perception-action coupling. Despite its importance, existing evidence on training effects is disproportionately focused on change-of-direction ability, overlooking the perceptual-cognitive demands of true agility. This systematic review therefore sought to quantify the effects of agility-specific training, examine moderators and establish dose-response model in team-sport players, while accounting for perception-action coupling. Following PRISMA 2020 guidelines, systematic searches were conducted in Web of Science, Scopus and PubMed for peer-reviewed English-language studies. Risk of bias was appraised using a modified Cochrane Collaboration's tool and study quality was evaluated via a tailored PEDro scale. Effect size (ES) was calculated using Hedge's g, and dependencies among multiple ESs within studies were addressed through three-level meta-analysis. Subgroup analyses and both linear and non-linear meta-regressions were performed to examine potential moderators and establish dose-response models. Twenty-eight studies met the inclusion criteria, of which 26 contributed 53 ESs to quantitative analyses. Agility training produced a large improvement in reactive agility test (RAT) performance (ES = 0.65, p < 0.01), a moderate improvement in pre-planned agility test (PAT) performance (ES = 0.55, p < 0.01), and a non-significant moderate effect in reaction test (RT) outcomes (ES = 0.52, p > 0.05). Training effects were moderated by participants' characteristics, with junior athletes (ES = 0.77, p < 0.05) and national level athletes (ES = 0.80, p < 0.05) demonstrating greater responses. However, female and mix-gender samples were underrepresented, and the evidence base was dominated by studies in soccer and basketball. Dose-response modelling revealed a curvilinear relationship between training duration and RAT (QM = 11.64, p < 0.01), peaking at 7-8 weeks and a positive linear association between training frequency and RAT (β = 0.172, p < 0.01). No significant relationship was observed between session time and RAT (p > 0.05), although most positive ESs clustered around 20-25 minutes per training session. Agility training exerts a large overall effect on RAT performance in team-sport players, with outcomes moderated by age and training status. Interventions of 7-8 weeks delivered at higher frequency (> 3 times/week) with 20-25 minutes session duration are frequently associated with favorable adaptions. These recommendations, however, should be interpreted cautiously given the moderate-to-low certainty of evidence, high within-study variability, dominance of soccer and basketball samples and potential risk of publication bias.

Association between weight-adjusted waist index (WWI) and multimorbidity: Evidence from NHANES and prospective validation in CHARLS.

To identify determinants of unbound bilirubin (UB) and assess whether the total bilirubin/albumin ratio (TB/Alb) can serve as a surrogate index in neonates. We retrospectively analyzed 2248 serum samples from 741 infants in a single neonatal intensive care unit (January 2022-October 2025). UB, total bilirubin (TB), direct bilirubin (DB), and albumin (Alb) were measured. Linear mixed-effects models with infant as a random effect accounted for repeated measurements and assessed determinants of UB and its association with TB/Alb. A mixed-effects logistic model evaluated the prediction of UB ≥ 0.6 µg/dL. Receiver operating characteristic analysis assessed the identification of UB ≥ 0.8 µg/dL using TB/Alb. UB increased with TB and DB and decreased with Alb. TB/Alb was strongly associated with UB and predicted UB ≥ 0.6 µg/dL. For UB ≥ 0.8 µg/dL, the optimal TB/Alb cutoff was 4.0 (sensitivity 0.94, specificity 0.85; area under the curve 0.95). In routine clinical samples, UB was primarily determined by TB and Alb concentrations. TB/Alb showed a clear dose-response relationship with UB and accurately identified high UB, supporting its use when direct UB measurement is unavailable. Unbound bilirubin (UB), the biologically relevant fraction associated with neurotoxicity, is difficult to measure routinely in many neonatal units. In 2248 clinical samples from 741 infants, the total bilirubin/albumin ratio (TB/Alb) showed a strong linear association with UB (UB = 0.165 × TB/Alb - 0.116). TB/Alb = 4 identified high UB levels (≥0.8 µg/dL) with excellent discrimination (AUC 0.952; optimal cutoff 4.03). TB/Alb can serve as a practical surrogate for UB, enabling rapid bedside risk stratification where UB testing is unavailable.

Lipoprotein(a) [Lp(a)] is a recognized risk factor for atherosclerotic cardiovascular disease (ASCVD), but the shape and potential nonlinearity of its association remain uncertain. We assessed the linear and nonlinear associations between Lp(a) levels and ASCVD risk using observational and Mendelian randomization (MR) approaches. We analyzed 351,858 UK Biobank participants (2006-2023), stratified into Lp(a) percentiles: <70th, 70th-<80th, 80th-<90th, and ≥90th. Outcomes included ASCVD events from hospital, primary care, self-report, and death registry data. Cox models estimated the hazard ratios (HRs). MR analyses used a polygenic risk score from 10 Lp(a)-associated single-nucleotide polymorphisms, with nonlinearity tested by doubly ranked MR. Higher Lp(a) levels were associated with increased ASCVD risk. Compared with the <70th percentile, adjusted HRs (95% confidence interval) were 1.11 (1.07-1.16), 1.18 (1.14-1.22), and 1.25 (1.21-1.30) for the 70th-<80th, 80th-<90th, and ≥90th groups. Kaplan-Meier curves diverged early by group. Spline models suggested nonlinearity with an inflection near 130 nmol/L (P=0.007). MR showed a 2% higher ASCVD risk per 10 nmol/L genetically predicted Lp(a) (P<2×10-16). Nonlinear MR suggested steeper gradients at higher levels, though not statistically significant (P=0.087). Elevated Lp(a) concentrations were causally associated with ASCVD risk, showing a predominantly graded relationship with possible nonlinearity at very high levels, supporting routine Lp(a) measurement and the development of Lp(a)-lowering therapies.

This study investigated the association between the Endothelial Activation and Stress Index (EASIX) and both the prevalence and mortality of breast cancer (BC). Further, it explored the potential mediating role of the Systemic Inflammation Response Index (SIRI). Data were obtained from the National Health and Nutrition Examination Survey 2001 to 2018. Weighted logistic regression models were used to examine the association between EASIX and BC prevalence, while mediation analysis evaluated the contribution of SIRI. Weighted Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for BC mortality, and Kaplan-Meier curves compared survival across EASIX levels. Restricted cubic spline regression assessed linearity, and subgroup analyses tested consistency across covariates. Among 21,329 participants, 593 BC cases were identified. Each 1-unit increase in EASIX was associated with a 39% higher BC risk (odds ratios [ORs] = 1.39, 95% CI: 1.07-1.82, P = .016). Compared with the lowest tertile (T1), the risk was elevated in T2 (OR = 1.61, 95% CI: 1.15-2.26, P = .006) and markedly higher in T3 (OR = 3.07, 95% CI: 2.28-4.14, P < .001). SIRI showed a modest but significant mediating effect, explaining 2.26% of the association (P = .034). No significant interactions were detected. In Cox models, each 1-standard deviation increase in EASIX was associated with a 56% higher risk of all-cause mortality (HR = 1.56, 95% CI: 1.47-1.65, P < .001) and a 104% higher risk among BC patients (HR = 2.04, 95% CI: 1.40-2.98, P < .001). Compared with T1, all-cause mortality increased by 59% in T2 (HR = 1.59) and more than 3-fold in T3 (HR = 3.11). BC-specific mortality was also higher in T3 (HR = 1.16, 95% CI: 1.05-1.27, P = .012). Restricted cubic spline analyses confirmed a linear positive association between EASIX and both BC prevalence and mortality. Elevated EASIX was significantly associated with higher BC prevalence and mortality, partly mediated by systemic inflammation. EASIX may serve as a valuable biomarker for risk assessment and prognosis in BC.

Objective: To investigate risk factors for postoperative lymph node metastasis in patients with intrahepatic cholangiocarcinoma (ICC) after curative resection. Methods: This retrospective case-series study consecutively enrolled 230 patients who underwent initial curative hepatectomy and were pathologically confirmed as ICC at Peking University People's Hospital between January 2015 and September 2025. The cohort comprised 120 men (52.2%) and 110 women (47.8%), with an age(M(IQR)) of 59 (14) years (range:31 to 83 years). Multivariable logistic regression was performed to identify independent risk factors for lymph node metastasis. Overall survival (OS) and disease-free survival (DFS) were evaluated using the Kaplan-Meier method and Cox proportional hazards models. Subgroup analyses based on lymph node status (N0, N1, and Nx) were conducted to explore the impact of lymphadenectomy extent and postoperative adjuvant therapy on prognosis across subgroups. Restricted cubic spline (RCS) analysis was used to assess the association between lymph node ratio (LNR) and survival outcomes. Results: Among the 230 ICC patients, 144 underwent lymphadenectomy, with a lymph node metastasis rate of 38.9% (56/144). Multivariable logistic regression identified carcinoembryonic antigen>4.7 μg/L (OR=5.895, P=0.030), preoperative radiological lymphadenopathy (OR=11.822, P=0.006), and large duct type histological subtype (OR=18.224, P=0.001) as independent risk factors for lymph node metastasis. Survival analyses showed that lymph node metastasis was associated with shortened OS and DFS (both P<0.01). In subgroup analyses of lymphadenectomy, retrieval of≥6 lymph nodes prolonged DFS in the N1 group (P=0.004) but did not improve OS; in the N0 group, retrieval of<6 lymph nodes was associated with better OS and DFS compared with ≥6 nodes (both P<0.05). RCS analysis demonstrated a significant linear association between LNR and DFS (P=0.006), whereas no association was observed between LNR and OS (P=0.451). Regarding adjuvant therapy, adjuvant treatment improved OS in the overall cohort (P=0.039) but did not prolong DFS (P>0.05). In the N1 group, adjuvant therapy improved OS (P=0.031); in the N0 group, it improved DFS (P=0.031); however, no survival benefit was observed in the Nx group (both P>0.05). Conclusions: Elevated carcinoembryonic antigen, preoperative lymphadenopathy, and large duct type histological subtype are independent risk factors for postoperative lymph node metastasis in ICC. Lymph node status significantly affects prognosis. Patients with lymph node-positive disease may benefit from retrieval of≥6 lymph nodes and postoperative adjuvant therapy, whereas excessive lymphadenectomy should be avoided in lymph node-negative patients, in whom adjuvant therapy mainly contributes to delaying recurrence.