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Our study aimed to explore the correlation between age at smoking initiation and smoking cessation for the risk for stroke in China. We investigated 50,174 participants from one of the urban areas of China Kadoorie Biobank (CKB) Study. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for association between smoking and incidence of stroke were estimated using Cox regression model. During a median of 10.7 years of follow-up, 4370 total stroke cases were documented. Among men, comparing current smokers to never smokers, the HR of total stroke for current smokers was 1.279 (95% CI, 1.134–1.443) for total stroke. The HRs of total stroke were 1.344 (1.151–1.570) for those started smoking at age less than 20 years, 1.254 (1.090–1.443) for those started smoking at age 20–30 years, and 1.205 (1.012–1.435) for those started smoking at age 30 year and above, with a dose-response relation (P for trend, 0.004). Comparing former smokers to current smokers, in the low pack-year group, those stopped smoking at age less than 65 years had a 18.2% decreased risk for total stroke (0.818; 0.673–0.994). The decreased risk was not found in those stopped smoking at age 65 years and above. Similar results were observed in the high pack-year group. In conclusion, we found that current smokers had a higher stroke risk than never smokers, and the risk increased with a younger age at smoking initiation. Smoking cessation can reduce the risk for stroke, especially could benefit from cessation at a younger age. [ABSTRACT FROM AUTHOR]

This article aims to explore hub genes related to different clinical types of cases with COVID-19 and predict the therapeutic drugs related to severe cases. The expression profile of GSE166424 was divided into four data sets according to different clinical types of COVID-19 and then calculated the differential expression genes (DEGs). The specific genes of four clinical types of COVID-19 were obtained by Venn diagram and conducted enrichment analysis, protein–protein interaction (PPI) networks analysis, screening hub genes, and ROC curve analysis. The hub genes related to severe cases were verified in GSE171110, their RNA-specific expression tissues were obtained from the HPA database, and potential therapeutic drugs were predicted through the DGIdb database. There were 536, 266, 944, and 506 specific genes related to asymptomatic infections, mild, moderate, and severe cases, respectively. The hub genes of severe specific genes were AURKB, BRCA1, BUB1, CCNB1, CCNB2, CDC20, CDC6, KIF11, TOP2A, UBE2C, and RPL11, and also differentially expressed in GSE171110 (P < 0.05), and their AUC values were greater than 0.955. The RNA tissue specificity of AURKB, CDC6, KIF11, UBE2C, CCNB2, CDC20, TOP2A, BUB1, and CCNB1 specifically enhanced on lymphoid tissue; CCNB2, CDC20, TOP2A, and BUB1 specifically expressed on the testis. Finally, 55 drugs related to severe COVID-19 were obtained from the DGIdb database. Summary, AURKB, BRCA1, BUB1, CCNB1, CCNB2, CDC20, CDC6, KIF11, TOP2A, UBE2C, and RPL11 may be potential diagnostic biomarkers for severe COVID-19, which may affect immune and male reproductive systems. 55 drugs may be potential therapeutic drugs for severe COVID-19. [ABSTRACT FROM AUTHOR]

Alterations of N6-methyladenosine (m6A) methylation have been reported in the cerebral cortices of mouse and rat models of ischemic stroke (IS). However, the role of m6A methylation in human IS is still unknown. We assessed m6A levels in peripheral blood from patients with IS and healthy controls. A transient middle cerebral artery occlusion and reperfusion (tMCAO/R) mouse model, and an oxygen–glucose deprivation/reperfusion (OGD/R) model in A172 cells were established to further assess m6A levels. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing were performed in the peripheral blood of patients with IS and healthy controls. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were used to identify underlying biological processes. In this study, we found that global m6A levels were elevated in the peripheral blood of patients with IS, in the cerebral cortex of mice after tMCAO/R treatment and in A172 cells after OGD/R treatment. MeRIP-seq analysis identified 2115 altered m6A peaks in patients with IS, 1052 upregulated and 1063 downregulated. Downregulated methylated mRNAs were enriched in Hippo signaling pathway, cytokine-cytokine receptor interaction, NF-kappa B signaling pathway, etc. Upregulated methylated mRNAs were enriched in calcium signaling pathways, Hedgehog signaling pathway, MAPK signaling pathway, etc. Moreover, a total of 84 differentially expressed mRNAs with altered m6A peaks were identified and enriched in EGFR tyrosine kinase inhibitor, Hematopoietic cell lineage, and cytokine-cytokine receptor interactions. This study is the first to profile the transcriptome-wide m6A methylome of peripheral blood in human IS and uncover increased global m6A levels in the peripheral blood of patients with IS. [ABSTRACT FROM AUTHOR]