It has been increasingly recognized that, to a significant extent, the peripheral immune system is playing a role in the etiology of Parkinson’s disease (PD). It has been reported recently that there may be multiple types of genetic susceptibility factors influencing the risk of PD through alterations in the functions of particular immune cells; at present, the precise mechanisms involved remain unclear. Based on a multi-dimensional causality inference model that included data from genome-wide association studies (GWAS), expression quantitative trait loci (eQTL), protein quantitative trait loci (pQTL) and single-cell eQTL (sc-eQTL), we performed both cross-tissue Mendelian randomization (MR) analysis and immune cell-specific MR analysis to investigate the association between genetic risk factors and peripheral immune functions based on individuals with PD. We found that the genetic prediction of CPNE1 expression had a negative association with PD risk in whole blood, substantia nigra and several immune cell types. The results support a possible protective relationship between CPNE1 and PD risk; however, the subsequent biological mechanism remains unclear. Genetically predicted CPNE1 expression showed a significant association with lower PD risk at the level of immune cells in nine different subtypes: T cells, monocytes, natural killer cells and so on. In addition, the exploratory immune-infiltration analysis of peripheral-blood transcriptomics data showed that there was a positive correlation of CPNE1 expression with the inferred number of regulatory T-cells; therefore, this result requires confirmation in subsequent studies. Our results suggest that CPNE1 could be a candidate factor for the reduced PD risk in blood, substantia nigra and several immune cell subsets. The above results suggest that peripheral immune regulation is likely associated with the link between CPNE1-relevant pathways and PD; however, it cannot determine the intermediate steps linking peripheral immune effects to neuroprotection in the brain.
Severe sepsis leads to damage of multiple organs, among which the lung is the most commonly damaged organ, yet its underlying mechanisms and therapeutic strategies are incompletely understood. Western blot and Immunohistochemistry analyses were performed to detect expression levels of related genes. HE staining was used to assess the severity of lung injury. Transmission electron microscopy (TEM) was employed to explore morphological alterations in cells. The C11 BODIPY 581/591 kit was used to detect the lipid peroxidation activity. Differentially expressed potential key genes of sepsis-induced acute lung injury (ALI) were screened out through GEO database mining, among which Lipocalin 2 (LCN2) played the most important role in the development of ALI, and mechanistic studies confirmed that LCN2 aggravated sepsis-induced ALI by inhibiting MUC1 to activate ER-stress-autophagy induced ferroptosis via lactate/MCT1/AMPK/mTOR axis. Finally, molecular docking technology was used to identify sorafenib as a potential therapeutic compound for ALI based on LCN2. Further studies showed that sorafenib improved the survival rate of septic mice and alleviated lung injury. This study revealed the key pathogenic role and underlying mechanisms of LCN2 in sepsis-induced ALI, and provided sorafenib as one of new targets and therapeutic strategies.
ObjectiveTo characterize the serum steroid hormone profile in reproductive-age women with systemic lupus erythematosus (SLE) and evaluate its associations with clinical manifestations and disease activity.MethodsThis cross-sectional study enrolled 39 newly diagnosed, treatment-naïve female SLE patients and 37 matched healthy controls. Fasting blood samples were collected in the morning. Serum levels of a comprehensive panel of steroid hormones (including glucocorticoids, mineralocorticoids, androgens, estrogens, and progestogens) were simultaneously quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Clinical parameters and disease activity (SLEDAI-2000) were assessed.ResultsSLE patients exhibited a globally altered steroid hormone profile compared to controls. Levels of key androgens (androstenedione, testosterone, dihydrotestosterone, dehydroepiandrosterone), glucocorticoids (cortisol, corticosterone, cortisone), and mineralocorticoids (aldosterone) were significantly lower in the SLE group. In contrast, serum melatonin was markedly elevated. Analysis across menstrual phases revealed consistently lower progesterone and 17-hydroxyprogesterone, but higher estradiol levels in SLE patients. Correlation analyses demonstrated that lower glucocorticoid and androgen levels were associated with increased inflammatory markers (e.g., lower complement C3/C4, higher IL-6) and hematological abnormalities. Crucially, reduced aldosterone levels correlated with higher 24-hour proteinuria and SLEDAI scores.ConclusionReproductive-age women with SLE display a distinct steroid hormone signature suggestive of hypothalamic-pituitary-adrenal (HPA) axis suppression, characterized by a broad deficiency in adrenal and gonadal steroids alongside hyperestrogenism and elevated melatonin. These hormonal imbalances are significantly correlated with disease activity, inflammation, and renal involvement. The serum steroid hormone profile may serve as a valuable biomarker for assessing SLE activity and provides insights into the endocrine-immune interplay in this disease.
Postoperative pulmonary complications (PPCs) are severe and are of particular concern in older adult patients undergoing laparoscopic gastrointestinal surgery. Both 40
Background:In-hospital adverse events remain a leading cause of preventable harm, and nurses play a pivotal role in hospital-wide risk management. The dual prevention mechanism-integrating tiered risk classification with hidden-danger investigation-is well established in occupational safety but rarely operationalised across hospital-wide nursing services. We evaluated an integrated nursing risk-management system grounded in this mechanism. Methods:In a 2-year, prospective, quasi-experimental implementation study (July 2022-July 2024) at Chifeng Municipal Hospital (Inner Mongolia, China), 49 clinical departments were allocated, at the unit level, to routine nursing management (control) or a structured dual-prevention system (intervention). Within these clusters, 120 nurses and 120 patients (60 + 60) were sampled. Outcomes were nursing-staff motivation, work quality, risk-management competence, the incidence of six adverse-event categories, and stakeholder satisfaction. Cluster-adjusted analyses used generalised estimating equations with Bonferroni correction; effect sizes are reported with 95% confidence intervals (CIs). Reporting followed SQUIRE 2.0 and TREND statement. As allocation was non-randomised, all estimates were interpreted as associations rather than causal effects. Results:Baseline characteristics and foundational competence were equivalent between groups. After 2 years, intervention nurses showed higher self-assessed motivation (Δ = +9.3 points; 95% CI 7.2 to 11.4), peer-assessed motivation (Δ = +7.4; 95% CI 5.4 to 9.4), and higher work-quality scores (83.81 ± 5.65 vs. 77.24 ± 5.82; Cohen's d = 1.15). Total adverse-event incidence was lower in intervention than in control clusters (11.67% vs. 31.67%) (cluster-adjusted OR = 0.29; 95% CI 0.11 to 0.75; p = 0.008). Patient and physician satisfaction increased to 93.3 and 92.0%, respectively. Basic nursing competence was unchanged, indicating the selective improvement of higher-order behaviours. Conclusion:The dual-prevention system was associated with broad competence gains, fewer adverse events, and higher satisfaction. Given the non-randomised design, these findings should be regarded as preliminary. Further confirmation through multicentre cluster-randomised confirmation is warranted.
