This study aimed to explore the molecular mechanism of estrogen-mediated neuroprotection in the relief of cerebral ischemic injury. The gene expression profiles were downloaded from Gene Expression Omnibus database, and differentially expressed genes (DEGs) were identified using limma package in R software. Further, DEGs were subjected to Gene Ontology (GO) cluster analysis using online Gene Ontology Enrichment Analysis Software Toolkit and to GO functional enrichment analysis using DAVID software. Using the Gene Set Analysis Toolkit V2, enrichment analysis of Kyoto Encyclopedia of Genes and Genomes pathways was performed. In addition, protein-protein interaction (PPI) network was constructed using STRING database, and submodule analysis of PPI network. Lastly, the significant potential target sites of microRNAs (miRNAs) were predicted using Molecular Signatures Database, and the function analysis of targets of predicted miRNA was also performed using DAVID software. In total, 321 DEGs were screened in the estrogen-treated sample. The DEGs were mainly associated with intracellular signaling and metabolic pathways, such as calcium channel, calcineurin complex, insulin secretion, low-density lipoprotein reconstruction, and starch or sugar metabolism. In addition, GO enrichment analysis indicated an altered expression of the genes related to starch and sucrose metabolism, retinol metabolism, anti-apoptosis (eg., BDNF and ADAM17) and response to endogenous stimulus. The constructed PPI network comprised of 243 nodes and 590 interaction pairs, and four submodules were obtained from PPI network. Among the module d, four glutamate receptors as Gria4, Gria3, Grin3a and Grik4 were highlighted. Further, 5 novel potential regulatory miRNAs were also predicted. MIR-338 and MIR520D were closely associated with cell cycle, while the targets of MIR-376A and MIR-376B were only involved in cell soma. The DEGs in estrogen-treated samples are closely associated with calcium channel, glutamate induced excitotoxicity and anti-apoptotic activity. In addition, some functionally significant DEGs such as BDNF, ADAM17, Gria4, Gria3, Grin3a, Grik4, Gys2 and Ugtla2, and new miRNAs like MIR-338 and MIR-376A were identified, which may serve as potential therapeutic targets for the effective treatment of cerebral ischemic injury.

This study was to investigate the protective effects of tea polyphenols on the blood-brain barrier (BBB) of rats with global cerebral ischemia/reperfusion (GCIR) injury. Sprague Dawley rats underwent four-vessel occlusion to construct the model of GCIR. Half an hour before complete occlusion, they were treated with tea polyphenols (TP) (6.4%; 100 or 200 mg/kg) via tail intravenous injection. 24 h after reperfusion, BBB permeability was evaluated by measuring brain water content (BWC) and residual amount of Evan’s blue dye in cerebral tissue. In addition to this, MMP-9 and collagen IV protein expression in cerebral tissue were also detected using immunohistochemistry. ANOVA and SNK-q were used to do statistical analysis. Statistical significance was considered at P

While platelet counts are known prognostic markers in acute myocardial infarction (AMI), the predictive value of dynamic platelet trajectories and their nonlinear association with nadir platelet counts remains unexplored. We aimed to identify distinct platelet trajectory patterns and evaluate their independent association with 28-day mortality in AMI patients. Using the MIMIC-IV database, we analyzed longitudinal platelet counts during the first 4 days of ICU admission in 3,657 AMI patients, Platelet trajectory patterns were identified using an unsupervised clustering approach combining factor analysis and k-means clustering based on 24 predefined summary measures describing temporal platelet dynamics. Patients were classified into ascending (AS), stable (ST), and descending (DS) trajectory groups. Associations with 28-day mortality were assessed using multivariate logistic regression, inverse probability weighting (IPW), and doubly robust estimation, with the DS group as the reference. Restricted cubic spline analysis was used to evaluate nonlinear relationships between nadir platelet counts and mortality. The cohort (median age 65 years; 58% male) revealed three distinct platelet trajectories: ascending (AS, n = 860), stable (ST, n = 2,270), and descending (DS, n = 527). Compared to the high-risk DS group, both AS (OR = 0.42, 95% CI 0.33–0.54) and ST (OR = 0.48, 95% CI 0.39–0.59) groups showed significantly lower 28-day mortality (all p < 0.001), with consistent results in IPW (AS: OR = 0.45; ST: OR = 0.51) and doubly robust models (AS: OR = 0.43; ST: OR = 0.49). Nadir platelet counts demonstrated a significant J-shaped association with mortality (P-nonlinear < 0.001), with the lowest estimated mortality risk observed at approximately 168 × 10⁹/L. Ascending/stable platelet trajectories are associated with reduced mortality risk compared to descending patterns in AMI, while extreme nadir values independently predict poor outcomes. Dynamic monitoring of platelet trajectories and nadir platelet levels may provide additional prognostic information for early risk stratification in AMI patients.

Background: Postoperative delirium is a frequent complication after cardiac surgery. The predictive value of initial lactate at ICU admission for cardiac surgery–associated postoperative delirium (CS-POD) remains unclear. Methods: We conducted a retrospective cohort study using the eICU Collaborative Research Database, including adult patients admitted to the ICU after cardiac surgery. Multivariable logistic regression, restricted cubic spline analysis, ROC analysis, and mediation analysis were performed to assess the association between initial lactate and CS-POD and to explore whether disease severity scores (SOFA, APACHE IV) or clinical interventions statistically explained this relationship. Results: Among 358 patients, 104 (29.1%) developed CS-POD. Higher initial lactate at ICU admission was independently associated with increased risk of CS-POD after full adjustment (OR per 1 mmol/L increase: 1.37, 95% CI 1.11–1.69; P = 0.003). Restricted cubic spline analysis demonstrated a linear relationship between initial lactate and CS-POD risk (P for nonlinearity = 0.132). Adding initial lactate to the baseline prediction model improved discriminative performance, with the area under the ROC curve (AUC) increasing from 0.661 (95% CI, 0.598–0.723) to 0.717 (95% CI, 0.660–0.775) (DeLong test P = 0.012). The optimal lactate cutoff for predicting CS-POD was 2.385 mmol/L. Mediation analysis indicated that part of the association between initial lactate and CS-POD was statistically explained by SOFA (proportion statistically explained: 17%, P = 0.002) and APACHE IV (proportion statistically explained: 7.7%, P = 0.034), whereas clinical interventions (IABP, RRT, opioid use) did not show significant mediation. Higher initial lactate levels were also associated with increased risks of acute kidney injury (OR 1.27, 95% CI 1.00–1.61) and in-hospital mortality (OR 2.88, 95% CI 1.52–5.46). Conclusions: Higher initial lactate at ICU admission is associated with an increased risk of CS-POD and adverse postoperative outcomes. However, its predictive value is modest and should be interpreted cautiously as part of a broader clinical assessment rather than as an independent decision-making tool.