Background and Purpose: The dynamic systemic inflammation level and stroke-associated infection (SAI) are related to the prognosis of acute ischemic stroke (AIS). We aimed to explore whether the systemic inflammatory response index (SIRI), systemic immune inflammation index (SII), and their dynamic changes possess predictability for SAI and long-term prognosis. Methods: A total of 1804 AIS patients without intravenous thrombolysis in two hospitals were included. We explored the relationship between SIRI, SII, and their dynamic changes and outcomes by constructing clusters. The mediating effects of SAI between prognosis and systemic inflammation were further evaluated. Results: Each SD increase in the concentration of SIRI exhibited a significant correlation with the risk of poor functional outcome, mortality, and functional dependency. Through K-means clustering analysis, patients with dramatically elevated or decreased systemic inflammation levels of SIRI (OR: 2.293, 95% CI: 1.279– 4.109) and SII (OR: 3.165, 95% CI: 1.627– 6.156) within 7 days had a higher risk of functional outcome. Through mediation analysis, SAI mediated the association between systemic inflammation and poor prognosis (SIRI: 33.73%, SII: 16.01%). Conclusion: Dramatically changing dynamics of SIRI and SII were significantly associated with a higher risk of poor prognosis in AIS patients. SAI mediated the association between systemic inflammation and prognosis at 1 year.

Background: Hearing loss (HL) is increasingly recognized as a significant global public health issue, and research on its relationship with vitamin D levels has gained wider attention. However, the association between serum biomarkers 25-hydroxyvitamin D₂ (25(OH)D₂) and D₃ (25(OH)D₃) with different types of HL remains unclear. This study aimed to investigate the potential association of serum 25(OH)D₂ and 25(OH)D₃ with HL in US adults.Methods: A sample of 3,684 individuals aged 20–69 years from the 2015–2016 National Health and Nutrition Examination (NHANES) was analyzed in this study. HL was defined as a pure tone average > 25 dB in either ear at low frequencies (500, 1,000, 2000 Hz), speech frequencies (500, 1,000, 2000, 4,000 Hz), and high frequencies (3,000, 4,000, 6,000, 8,000 Hz). Logistic regression was employed to examine the association between serum 25(OH)D₂ and 25(OH)D₃ and HL. The study population was then stratified by age, gender, race, and education level to analyze potential differences between adults in different subgroups.Results: In the multivariate analysis, it was found that serum 25(OH)D₂ was independently associated with low-frequency hearing loss (LFHL) (OR: 1.012 [95% CI, 1.005–1.020]) and speech-frequency hearing loss (SFHL) (OR: 1.011 [95% CI, 1.003–1.018]). Restrictive cubic spline analysis demonstrated a linear dose–response relationship between serum 25(OH)D₂ levels and LFHL (p for linearity <0.001), as well as SFHL (p for linearity = 0.001). Conversely, an L-shaped association was observed between serum 25(OH)D₃ levels and both LFHL (p for nonlinearity = 0.014) and SFHL (p for nonlinearity = 0.025), with threshold values identified at 35.3 and 36.5 nmol/L, respectively. Higher levels of serum 25(OH)D₃ were associated with a lower probability of high-frequency hearing loss (HFHL) (OR: 0.994 [95% CI, 0.989–0.999]), with a threshold value identified at 53.9 nmol/L. Furthermore, a significant interaction between diabetes and serum 25(OH)D₂ in LFHL was revealed through subgroup analysis (p = 0.041). In the non-diabetic population, serum 25(OH)D₂ maintained its association with LFHL.Conclusion: Our findings suggested a positive association between serum 25(OH)D₂ concentrations and both LFHL and SFHL in the studied cohort. Additionally, an L-shaped relationship was found between serum 25(OH)D₃ and LFHL and SFHL, and higher levels of serum 25(OH)D₃ were identified to be associated with a lower risk of HFHL.

Migraine is a highly prevalent neurological disorder with complex pathophysiology and limited treatment efficacy. Emerging evidence suggests immune cell involvement in migraine, but the specific regulatory mechanisms remain unclear. This study aimed to identify immune cell-type-specific genetic drivers of migraine and prioritize potential therapeutic targets. We conducted a Mendelian randomization (MR) analysis integrating single-cell expression quantitative trait loci (sc-eQTL) data from 14 immune cell types with large-scale genome-wide association studies (GWAS) of migraine. Colocalization analysis, protein-protein interaction (PPI) networks, linkage disequilibrium score regression (LDSC), phenome-wide association studies (PheWAS), and drug repurposing databases were utilized to validate findings and assess therapeutic potential and safety. We identified 25 immune cell-specific eGenes causally associated with migraine, including CDC42, NELFCD, HOXB3, HAX1, and FHL3. Several genes, such as CDC42 and HAX1, were implicated across multiple immune cell types. Subtype-specific analyses revealed differential gene effects in migraine with aura (MA) and without aura (MO). Genetic correlation and pleiotropy analyses linked eGenes to comorbid traits such as depression, gastrointestinal disorders, and blood pressure. PheWAS suggested minimal adverse associations for prioritized genes like GINM1 and TMA7. Drug repurposing identified FDA-approved agents, including hydroxychloroquine sulfate (NELFCD) and bazedoxifene (CDC42), as potential migraine therapies. This study reveals immune cell-specific genetic contributors to migraine and highlights druggable targets for therapeutic development. Integrating sc-eQTL with multi-omics and pharmacological data provides a novel framework for precision medicine in migraine.