Yanling Liang

Background and Aims The predictive value of the atherogenic index of plasma (AIP) and high-sensitivity C-reactive protein (hsCRP) for stroke is established; however, evidence is largely derived from diabetic cohorts, limiting the generalizability of findings to non-diabetic populations. We therefore conducted this study to specifically assess their combined and interactive associations with stroke in individuals without diabetes. Methods This study included 8,721 participants from the CHARLS baseline (wave1) with no history of stroke or diabetes at baseline. The AIP was calculated as lg[Triglycerides (mmol/L)/HDL-C(mmol/L)]. In a subset of 5,763 participants with repeated measurements, we further analyzed the associations of CumAIP and CumhsCRP with incident stroke. Results The results showed that compared to individuals with both low AIP and low hsCRP, those with elevated levels of both had the highest overall risk of stroke (adjusted Hazard Ratio [aHR]: 1.715; 95% Confidence Interval (CI): 1.380–2.130). Compared with the traditional risk factor model, the model adding AIP and hsCRP improved the AUC from 0.664 to 0.673 (P < 0.05), with a continuous Net Reclassification Improvement (NRI) of 0.182 (95% CI: 0.075–0.289) and Integrated Discrimination Improvement (IDI) of 0.009 (95% CI: 0.003–0.015).A total of 435 stroke events were observed during the 5-year follow-up subanalysis, individuals with high levels of both cumulative exposures also had a significantly increased risk (aHR: 1.421; 95% CI: 1.133–1.783).Furthermore, using repeated measurements, mediation analyses demonstrated no statistically significant mediating effect of hsCRP in the association between AIP and stroke. In contrast, AIP exerted a significant mediating effect, accounting for 11.6% of the total effect of hsCRP on stroke. Conclusions The study findings confirm that AIP and hsCRP exert combined effects on stroke risk among non-diabetic middle-aged and older adults. Notably, AIP plays a significant mediating role in the association between elevated hsCRP and stroke. Therefore, integrating both markers into risk assessment is recommended to refine primary stroke prevention and address residual risk among non-diabetic populations, particularly middle-aged adults.

Posterior reversible encephalopathy syndrome (PRES) in pregnancy, triggered by obstetric conditions, is a neuroradiological syndrome and a critical materna

Background Vestibular Migraine (VM) is a complex neurological disorder with recurrent headaches and various vestibular symptoms. Although it severely affects patients’ quality of life, its causes and pathophysiology are still unclear, and effective treatments are scarce. The lack of data emphasizes the need for bioinformatics to find key genes and pathways in VM, which could help develop new diagnostic and treatment methods. Method The GSE109558 dataset was acquired from the Gene Expression Omnibus (GEO) database. To identify VM - related differentially expressed genes, screening was carried out through limma and Weighted Correlation Network Analysis (WGCNA).The functional analysis of VM - related differentially expressed genes was conducted using three bioinformatics approaches: Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Gene Set Enrichment Analysis (GSEA). Feature selection was further refined using lasso regression and random forest. Also, CIBERSORT was utilized to analyze the infiltration of immune cells, and Spearman’s correlation analysis was employed to explore the correlations between diagnostic differentially expressed genes and immune cells.Finally, the Comparative Toxicogenomics Database (CTD) was utilized to search for corresponding drugs, and molecular docking was performed to explore potential therapeutic targets. Result Six key feature genes (CABIN1, IFIT3, HEATR1, ARHGDIA, RAB11FIP4, and ZNF444) were identified as potential diagnostic markers for VM. Among these, CABIN1 demonstrated the highest diagnostic potential based on ROC curve performance, highlighting its promise as a diagnostic biomarker.Functional annotation of DEGs revealed their enrichment in biological processes related to inflammation, calcium ion channel regulation, and other pathways likely involved in VM pathophysiology. Through the CTD, drugs like Acetaminophen, bisphenol A, and Phenylephrine were identified. Molecular docking simulation was used to explore their potential therapeutic mechanisms for VM. Conclusion This study offers important insights into the molecular mechanisms of VM and identifies six key feature genes, with CABIN1 standing out as a potential diagnostic marker.These findings pave the way for further research to validate the diagnostic and therapeutic implications of these genes and pathways.

Hypoxia is a prominent feature of head and neck cancer. However, the oxygen element characteristics of proteins and how they adapt to hypoxia microenvironments of head and neck cancer are still unknown. Human genome sequences and proteins expressed data of head and neck cancer were retrieved from pathology atlas of Human Protein Atlas project. Then compared the oxygen and carbon element contents between proteomes of head and neck cancer and normal oral mucosa-squamous epithelial cells, genome locations, pathways, and functional dissection associated with head and neck cancer were also studied. A total of 902 differentially expressed proteins were observed where the average oxygen content is higher than that of the lowly expressed proteins in head and neck cancer proteins. Further, the average oxygen content of the up regulated proteins was 2.54% higher than other. None of their coding genes were distributed on the Y chromosome. The up regulated proteins were enriched in endocytosis, apoptosis and regulation of actin cytoskeleton. The increased oxygen contents of the highly expressed and the up regulated proteins might be caused by frequent activity of cytoskeleton and adapted to the rapid growth and fast division of the head and neck cancer cells. The oxygen usage bias and key proteins may help us to understand the mechanisms behind head and neck cancer in targeted therapy, which lays a foundation for the application of stoichioproteomics in targeted therapy and provides promise for potential treatments for head and neck cancer.

The toll-like receptor 4 (TLR4) pathway is involved in seizures. We investigated whether ultrasound-targeted microbubble destruction (UTMD)-mediated delivery of short hairpin RNA (shRNA) targeting the TLR4 gene (shRNA-TLR4) can reduce ischemia-induced seizures in rats with hyperglycemia. A total of 100 male Wistar rats were randomly assigned to five groups: (1) Sham; (2) normal saline (NS); (3) shRNA-TLR4, where rats were injected with shRNA-TLR4; (4) shRNA-TLR4 + US, where rats were injected with shRNA-TLR4 followed by ultrasound (US) irradiation; and (5) shRNA-TLR4 + microbubbles (MBs) + US, where rats were injected with shRNA-TLR4 mixed with MBs followed by US irradiation. Western blot and immunohistochemical staining were used to measure TLR4-positive cells. Half of the rats in the NS group developed tonic-clonic seizures, and TLR4 expression in the CA3 region of the hippocampus was increased in these rats. In addition, the NS group showed an increased number of TLR4-positive cells compared with the Sham group, while there was a decreased number of TLR4-positive cells in the shRNA, shRNA + US, and shRNA + MBs + US groups. Our findings indicate that the TLR4 pathway is involved in the pathogenesis of ischemia-induced seizures in hyperglycemic rats and that UTMD technology may be a promising strategy to treat brain diseases.

Obstetric posterior reversible encephalopathy syndrome (PRES), caused by preeclampsia (PE) or eclampsia, is a clinical imaging syndrome and a critical maternal complication, with vasogenic edema in white matter as a typical imaging characteristic. Serum neurofilament light (NFL) is a marker of neuroaxonal injury. Therefore, we performed this study to explore the diagnostic and prognostic role of NFL in obstetric PRES. We used stored serum samples and clinical data obtained from 2148 PE or eclampsia patients from the Guangzhou Medical Centre for Critical Pregnant Women from January 2015 to January 2020. The serum NFL concentration was measured by Simoa assay. Patients without complete data and MRI examinations were excluded. All patients were grouped into the PRES and non-PRES groups based on the PRES diagnostic criteria. In total, 222 patients met the inclusion criteria and were grouped into the PRES (n = 123) and non-PRES (n = 99) groups. The NFL level was significantly higher in the PRES group than in the non-PRES group (p < 0.0001). The discriminatory accuracy of diagnostic panels (headaches + NFL, NFL) in receiver operating characteristic curve analysis (area under the curve) was 0.9338 and 0.7664. Importantly, the NFL level was significantly correlated with edema severity (Spearman’s correlation, p < 0.0001), and a poorer pregnancy outcome was observed in the PRES group. In conclusion, an increased NFL level can add predictive value for diagnosing obstetric PRES, and its level is associated with both clinical severity and pregnancy outcome, suggesting that NFL could serve as a diagnostic and prognostic biomarker for obstetric PRES.