中医药防治COVID-19的直接和间接调控作用研究进展

中医药在新冠疫情的防治过程中发挥了重要作用，不仅可以靶向病毒生命周期的多个节点、阻断病毒侵入和复制、发挥直接抗病毒作用，同时也可以通过增强机体免疫、抑制细胞因子风暴、调节肠道菌群等方式，调节机体稳态，发挥间接调控作用。因此，本研究基于系统论，将中西医思维有机融合，结合临床及实验研究进展，从直接调控、间接调控的新视角，综合阐释中医药防治新冠/新冠上呼吸道感染的综合作用机制。     

Circulating macrophage colony-stimulating factor levels and stroke: A Mendelian randomization study

ObjectivesColony-stimulating factor 1 (CSF1), also known as macrophage colony-stimulating factor, has been shown to be associated with risk of ischemic stroke in conventional epidemiological study. We performed a Mendelian randomization analysis to evaluate the effects of genetically predicted circulating CSF1 levels on stroke and carotid intima-media thickness (cIMT).MethodsGenetic variants robustly associated with CSF1 levels, located in the vicinity of the CSF1 gene (cis), were used as instruments for CSF1 levels. Genetic association estimates for ischemic stroke and its subtypes, intra-cerebral hemorrhage (ICH), and cIMT were obtained from MEGASTROKE (60,341 cases and 454,450 controls), ISGC (1,545 cases and 1,481 controls), and UK Biobank (22,179 individuals), respectively.ResultsGenetically predicted higher CSF1 levels was significantly associated with a higher risk of any ischemic stroke, large artery stroke (LAS) and cardioembolic stroke (CES), but not with small vessel stroke (SVS) and ICH. The odds ratios (ORs) per genetically predicted one standard deviation (SD) increase in circulating CSF1 levels were 1.11 (95% CI 1.04–1.17) for any ischemic stroke, 1.23 (95% CI 1.07–1.42) for LAS, 1.18 (95% CI 1.05–1.33) for CES, 1.07 (95% CI 0.94–1.21) for SVS, and 1.15 (95% CI 0.73–1.83) for ICH. Similarly, we also found that genetically predicted higher CSF1 levels were associated with higher cIMT, as a measure of subclinical atherosclerosis (cIMT, β 0.016, 95% CI, 0.004-0.029).ConclusionsThis study provides evidence that genetically predicted higher CSF1 levels was associated with higher risk of any ischemic stroke, LAS, and CES. Whether targeting CSF1 or its receptors can reduce the risk of ischemic stroke needs further study.     

Mechanistic analysis for the origin of diverse diterpenes in Tripterygium wilfordii

Tripterygium wilfordii is a valuable medicinal plant rich in biologically active diterpenoids, but there are few studies on the origins of these diterpenoids in its secondary metabolism. Here, we identified three regions containing tandemly duplicated diterpene synthase genes on chromosomes (Chr) 17 and 21 of T. wilfordii and obtained 11 diterpene synthases with different functions. We further revealed that these diterpene synthases underwent duplication and rearrangement at approximately 2.3–23.7 million years ago (MYA) by whole-genome triplication (WGT), transposon mediation, and tandem duplication, followed by functional divergence. We first demonstrated that four key amino acids in the sequences of TwCPS3, TwCPS5, and TwCPS6 were altered during evolution, leading to their functional divergence and the formation of diterpene secondary metabolites. Then, we demonstrated that the functional divergence of three TwKSLs was driven by mutations in two key amino acids. Finally, we discovered the mechanisms of evolution and pseudogenization of miltiradiene synthases in T. wilfordii and elucidated that the new function in TwMS1/2 from the terpene synthase (TPS)-b subfamily was caused by progressive changes in multiple amino acids after the WGT event. Our results provide key evidence for the formation of diverse diterpenoids during the evolution of secondary metabolites in T. wilfordii.     

近十年甘草栽培研究进展

近期新型冠状病毒肺炎(COVID-19)席卷全球,中医药全程参与COVID-19的治疗,甘草在所有免疫调节抗病毒中药以及中医临床处方中使用频次最高.作为药食同源的中药材大品种,甘草在人类生产生活的很多方面扮演着重要角色.甘草野生资源匮乏,栽培甘草年限短、质量差且不稳定,严重影响甘草的临床疗效与其他应用.作者在阅读近十年...