Da Zhou

BACKGROUND AND AIMS: Cardiovascular diseases (CVDs) have become a predominant cause of illness and death among adolescents and young adults globally, largely influenced by metabolic risks. This research sought to assess the worldwide impact of CVDs linked to metabolic risks in this demographic, using the most recent data from the 2021 Global Burden of Disease (GBD) study. METHODS: Information on CVDs and the associated metabolic risk factors was obtained from the GBD 2021 dataset. Spatial and temporal analyses of global and regional burdens were conducted, and the estimated annual percentage change was used to assess the trends. Projections of future trends were generated using Bayesian Age–Period–Cohort models. RESULTS: In 2021, metabolic risks caused 213,363 CVD deaths and 12,924,201 disability-adjusted life years (DALYs) among people aged 15–39 years globally. Although age-standardized death rates (ASDRs) and DALY rates generally decreased in the majority of regions over the past 30 years, the absolute numbers increased. Males and individuals aged 35–39 years were the most affected groups. Ischemic heart disease was the primary cause of death, with elevated systolic blood pressure and low-density lipoprotein cholesterol as the dominant metabolic risks. Projections indicate that the total number of metabolic-related CVD deaths will reach a peak in 2033 before declining. CONCLUSIONS: Although ASDRs and DALY rates have declined over the past 30 years, the absolute numbers have risen. The observed variations underscore the importance of developing focused prevention and intervention approaches to improve health outcomes in this vulnerable population.

Background: Idiopathic intracranial hypertension (IIH) is a multifactorial disorder characterized by sustained intracranial pressure (ICP) elevation in the absence of identifiable causes, predominantly affecting obese women of reproductive age. Although the pathophysiology of IIH remains incompletely understood, accumulating evidence indicates that inflammation is closely intertwined with metabolic, vascular, and cerebrospinal fluid (CSF) disturbances. Methods: We performed a structured literature search of PubMed, EMBASE, Web of Science, and the Cochrane Library for studies relevant to the pathophysiology of IIH, with a particular focus on inflammatory mechanisms, molecular signatures, and clinical correlates. Results: The reviewed evidence indicates that inflammatory activation within the choroid plexus and cerebral endothelium is associated with enhanced activity of sodium‐potassium adenosine triphosphatase (Na ⁺ /K ⁺ ‐ATPase), Na ⁺ ‐K ⁺ ‐2Cl ⁻ cotransporter (NKCC1), and aquaporin‐1 (AQP1), impaired barrier integrity, and increased CSF secretion. In parallel, inflammatory fibrosis of arachnoid villi and dysfunction of glymphatic–lymphatic outflow pathways may impede CSF reabsorption, further contributing to ICP elevation. At the systemic level, obesity‐associated adipokines, proinflammatory cytokines, and endocrine dysregulation—particularly involving glucocorticoid and sex‐steroid signaling—appear to amplify neuroinflammatory cascades linked to altered CSF homeostasis. Clinically, patients with IIH exhibit elevated inflammatory biomarkers (C‐reactive protein, neuron‐specific enolase, neutrophil‐to‐lymphocyte and platelet‐to‐lymphocyte ratios), intrathecal immunoglobulin G (IgG) synthesis, and increased neurofilament light chain levels, consistent with combined immune activation and neuroaxonal stress. Common comorbidities such as anemia, obstructive sleep apnea, and thrombophilia may further exacerbate inflammatory and hypoxic burden. Collectively, these findings support a conceptual shift from IIH as a purely mechanical disorder toward an immunometabolic disease of CSF regulation. Conclusions: In this review, we integrate mechanistic, clinical, and molecular evidence linking inflammation to IIH pathophysiology, and discuss how inflammatory biomarkers, metabolic modulators, and targeted anti‐inflammatory strategies could inform future diagnostic, prognostic, and therapeutic frameworks. A more precise understanding of these immunometabolic pathways may help redefine IIH as a biologically stratified and therapeutically tractable disorder.

BACKGROUND: Genetic predisposition is increasingly recognized as an important contributor to cerebral venous thrombosis (CVT), yet findings from individual studies remain inconsistent. We conducted an updated meta-analysis to quantify associations between specific genetic variants and adult CVT. METHODS: We systematically searched PubMed, EMBASE, and Web of Science up to January 2025 for case-control studies comparing the prevalence of genetic variants in adults with CVT versus healthy controls. Pooled odds ratios (ORs) with 95% CIs were calculated using random-effects models in this meta-analysis. RESULTS: Sixty-one studies comprising 4106 patients with CVT and 12 323 controls were analyzed. Significant associations were identified for germline variants, including factor V Leiden (238/2753 [8.6%] versus 387/8747 [4.4%]; OR, 2.59 [95% CI, 2.06–3.26]; P prothrombin G20210A (290/2483 [11.7%] versus 235/8197 [2.9%]; OR, 6.05 [95% CI, 4.59–7.98]; P protein C (24/624 [3.8%] versus 7/2027 [0.3%]; OR, 10.30 [95% CI, 4.19–25.30]; P protein S (9/567 [1.6%] versus 1/1125 [0.1%]; OR, 6.86 [95% CI, 2.12–22.24]; P =0.001), and antithrombin (11/440 [2.5%] versus 3/989 [0.3%]; OR, 5.73 [95% CI, 1.98–16.55]; P =0.001). The somatic JAK-2 (Janus kinase-2) V617F mutation was likewise associated with increased risk (27/569 [4.7%] versus 13/1777 [0.7%]; OR, 9.17 [95% CI, 3.61–23.27]; P MTHFR (methylenetetrahydrofolate reductase) C677T and PAI-1 (plasminogen activator inhibitor-1) 4G/5G polymorphisms showed no significant associations. Overall effect sizes were comparable to those reported in pediatric CVT but exceeded those in adult arterial ischemic stroke. CONCLUSIONS: These findings support a genetic basis for adult CVT. Risk associations are broadly similar to pediatric CVT yet stronger than those reported for adult arterial ischemic stroke, highlighting distinct patterns of genetic susceptibility in venous stroke and the potential value of selective genetic testing for risk stratification and management.

Elevated lactate dehydrogenase (LDH) has been linked to unfavorable outcomes across various diseases, yet its prognostic relevance in critically ill patients with ischemic stroke (IS) remains insufficiently defined. This study aimed to investigate whether LDH levels at admission to the intensive care unit (ICU) are independently associated with short-term mortality among IS patients requiring critical care. This retrospective cohort study utilized data from the Medical Information Mart for Intensive Care (MIMIC-IV, version 3.1) database. The primary and secondary endpoints were all-cause in-hospital mortality and 30 day mortality, respectively. Associations between LDH and outcomes were evaluated using Kaplan-Meier survival curves, multivariable Cox proportional hazards models, and restricted cubic splines (RCS) analyses. Discriminative performance was assessed by time-dependent receiver operating characteristic (ROC) curves and concordance index (C-index). Incremental prognostic value beyond established clinical scores (SAPS II, APS III, OASIS, and LODS) was quantified using category-free net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Of 818 patients, higher LDH was associated with worse survival (log-rank P < 0.001). After full adjustment, LDH remained independently associated with in-hospital death (36.6% vs. 7.0%; HR 2.82, 95% CI 1.46-5.46; P = 0.002) and 30 day mortality (41.0% vs. 14.8%; HR 2.07, 95% CI 1.24-3.44; P = 0.005). However, results for 30 day mortality attenuate to non-significance after full adjustment in sensitivity analysis (41.0% vs. 14.8%; HR 1.45, 95% CI 0.97-2.17; P = 0.068). RCS modeling revealed a nonlinear relationship, with mortality risk rising sharply above approximately 268 IU/L. Log-transformed LDH demonstrated modest discriminative ability for both in-hospital (AUC 0.642, 95% CI 0.583-0.701; C-index = 0.657, 95% CI 0.612-0.702) and 30 day mortality (AUC 0.668, 95% CI 0.629-0.707; C-index = 0.652, 95% CI 0.617-0.687). Incorporating LDH into conventional severity scores modestly but significantly improved discrimination (positive NRI and IDI). Admission LDH levels are independently associated with in-hospital and 30 day mortality among critically ill IS patients and may serve as a potential adjunct to established prognostic tools for early risk stratification. External, multicenter validation is warranted to confirm these findings.

Aims: This study aimed to characterize the clinical features of headache in patients with non‐thrombotic internal jugular vein stenosis (IJVS) and to identify associated risk factors. Methods: This retrospective study consecutively enrolled patients with imaging‐confirmed non‐thrombotic IJVS from January 2021 through July 2024. Participants were divided into IJVS‐headache and IJVS‐without‐headache groups based on clinical symptoms. Demographic, clinical, neuroimaging, and treatment data were reviewed in detail. Univariate and multivariate logistic regression analyses were performed to determine risk factors for headache. Results: Among 283 eligible patients (median age: 51 years in the IJVS‐headache group vs. 56 years in the IJVS‐without‐headache group, p < 0.001), 65.02% reported headache. Most headaches were chronic (82.07%), generalized (85.87%), and moderate in intensity (53.26%), with notable daily life impact (57.61%). Univariate analysis showed that headache was significantly associated with visual disturbances ( p = 0.010), elevated cerebrospinal fluid opening pressure ( p < 0.001), high jugular bulb ( p = 0.007), and severe scalp vein dilation ( p < 0.001), but inversely associated with severe vertebral vein expansion ( p < 0.001). Multivariate regression revealed that high jugular bulb (OR = 3.144, 95% CI: 1.083–9.123, p = 0.035), severe scalp vein dilation (OR = 2.142, 95% CI: 1.068–4.294, p = 0.032), and protein C or S deficiency (OR = 5.984, 95% CI: 1.196–29.928, p = 0.029) were independent risk factors, whereas severe vertebral vein expansion was protective (OR = 0.184, 95% CI: 0.092–0.366, p < 0.001). Conclusions: Headache represents a prevalent and often disabling symptom in non‐thrombotic IJVS, underpinned by distinctive vascular and hematologic profiles. Identification of high‐risk patients based on neuroimaging and thrombophilia screening may facilitate personalized interventions and improve symptom control.

The causal relationships between attention-deficit/hyperactive disorder (ADHD) and vascular risk factors remain insufficiently understood. This study aimed to comprehensively investigate the causal effects of ADHD on vascular risk factors and identify crucial mediators in these relationships. Utilizing instrumental variables from genome-wide association study (GWAS) datasets, we applied two-sample Mendelian randomization (MR) to explore the causal influences of ADHD on adiposity-related traits, blood pressure regulation, glucose metabolism, lipid profiles, lifestyle habits, chronic kidney disease, and systemic inflammation. Additionally, two-step MR was employed to evaluate the mediating effect of educational attainment (EA) in each newly established causal pair. Genetically determined ADHD was causally linked to increased body mass index (BMI, β = 0.054, p = 1.01E-08), waist-to-hip ratio (WHR, β = 0.041, p = 1.65E-07), waist circumference (WC, β = 0.048, p = 5.78E-15), body fat percentage (BF%, β = 0.024, p = 7.19E-05), risk of type-2 diabetes mellitus (T2DM, OR = 1.104, p = 6.07E-07), and number of cigarettes smoked per day (β = 0.094, p = 3.99E-06), earlier smoking initiation (β = 0.115, p = 2.71E-12), and higher levels of C-reactive protein (CRP, β = 0.054, p = 6.35E-14). Furthermore, EA was demonstrated to play a key mediating role in these causal relationships, with mediation proportions ranging from 41.67% to 11.30%. Our MR analyses supported the causal impacts of ADHD on several vascular risk factors, including BMI, WHR, WC, BF%, T2DM, early smoking initiation, cigarettes consumed per day, and CRP. Moreover, we recognized EA as a critical mediator underlying the established causal pathways. Overall, this study highlighted that individuals with ADHD were more likely to suffer from obesity, T2DM, poor lifestyle habits, and intense inflammation.

Cerebral venous thrombosis (CVT) is an uncommon yet potentially life-threatening subtype of stroke that predominantly affects younger individuals. This study aimed to systematically identify and validate druggable genes associated with CVT susceptibility using Mendelian randomization (MR) approaches. We integrated two large-scale expression quantitative trait loci (eQTLs) datasets - eQTLGen (peripheral blood) and PsychENCODE (brain tissue) - as exposures, with CVT genome-wide association study (GWAS) summary statistics from FinnGen serving as the outcome. A two-sample MR (TSMR) framework was employed, supported by sensitivity analyses, summary-data-based MR (SMR), and Bayesian colocalization. Functional enrichment, single-cell analyses, drug prediction, and molecular docking were further performed to explore biological relevance and therapeutic potential. TSMR identified 19 candidate genes from blood eQTLs after false discovery rate (FDR) correction; two were excluded due to pleiotropy, leaving 17, among which 10 were supported by SMR and colocalization. An additional nominally significant gene (ZP3) was detected from brain tissue. Of these, IL18, BMPR2, and COMT exhibited the strongest evidence. Functional annotation implicated these genes in cytokine signaling, cellular adhesion, and coagulation pathways. Single-cell RNA sequencing localized their expression mainly to monocytes, dendritic cells, and natural killer cells. Drug repurposing and docking analysis suggested potential inhibitory interactions between IL18 and glucocorticoids/pioglitazone, and between BMPR2 and iloprost. This study reveals novel gene networks potentially involved in CVT pathogenesis and prioritizes IL18, BMPR2, and COMT as promising candidates for future therapeutic development. Nonetheless, these findings are based on genetic inference and require further mechanistic and clinical validation.

Background: Cerebral venous thrombosis (CVT) is a rare but life-threatening condition, particularly among pregnant and postpartum women. However, estimates of its incidence, recurrence, and associated adverse outcomes remain inconsistent. Moreover, the role of antithrombotic prophylaxis in mitigating these risks has not been fully established. Objective: This study aimed to synthesize global evidence on the incidence of CVT during pregnancy and postpartum, evaluate recurrence rates of CVT and noncerebral venous thromboembolism (VTE), assess adverse pregnancy outcomes, and explore the efficacy and safety of antithrombotic prophylaxis in high-risk populations. Methods: A systematic review and meta-analysis was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Five major databases were searched for observational studies reporting CVT incidence, recurrence, or pregnancy outcomes in women with prior CVT or noncerebral VTE, covering the period from 1980 to September 2024, with an updated search completed on May 6, 2025. Data were pooled using random-effects models and heterogeneity was quantified via the I ² statistic. Results: Forty-seven studies encompassing 14,218 pregnancies were included. The pooled incidence of postpartum CVT was 7 cases per 100,000 deliveries (95% confidence interval [CI]: 3–15), with significant regional disparities (Asia: 19/100,000; Europe: 3/100,000). The recurrence rate of CVT was 10.2 per 1000 deliveries (95% CI: 5–21), while noncerebral VTE recurred in 15.3 per 1000 pregnancies (95% CI: 8–28). The crude risk of spontaneous abortion was 15.7% (95% CI: 13–19), with higher rates observed in women not receiving prophylaxis. Antithrombotic prophylaxis appeared to reduce the risk of noncerebral VTE recurrence but did not significantly affect CVT recurrence. Conclusions: CVT and noncerebral VTE pose substantial risks during pregnancy, particularly in women with prior thrombotic events. Although antithrombotic prophylaxis may offer partial protection, its benefits must be carefully weighed against potential maternal and fetal risks. These findings underscore the need for individualized management and further research to inform evidence-based clinical guidelines.