目的 构建桃红四物汤干预腰椎间盘突出症的“药物- 靶基因- 疾病”预测模型,探究桃红四物汤治疗腰椎间盘突出症的核心靶点及作用通路。方法 〖JP3〗通过中药系统药理学数据库与分析平台收集桃红四物汤中有效的化学成分及靶点信息,运用UniProt蛋白质数据库实现基因靶点名称规范化;从GeneCards、疗效靶点数据库、人类孟德尔遗传在线、DRUGBANK数据库中查找腰椎间盘突出症的靶点。构建“成分- 靶点- 疾病”网络,并对蛋白相互作用(protein- protein interaction,PPI)网络进行可视化分析,分析排名前20个靶点的生物过程、分子功能、细胞组成和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)中信号通路。结果 筛选出69个桃红四物汤的有效化学成分,235个潜在基因靶点,其中与腰椎间盘突出症共同的基因靶点有82个。PPI网络分析显示,肿瘤坏死因子(tumor necrosis factor,TNF)、表皮生长因子(epidermal growth factor,EGF)、表皮生长因子受体(epidermal growth factor receptor, EGFR)、激活蛋白1(activator protein 1,JUN)、丝氨酸/苏氨酸蛋白激酶(serine/threonine- protein kinase 1,AKT1)是桃红四物汤干预腰椎间盘突出症的核心靶点。基因本体论的富集分析结果显示,桃红四物汤干预腰椎间盘突出症的过程涉及对DNA结合转录因子活性的调节、细胞对生物刺激的反应、氧化应激反应以及对脂多糖、细菌来源分子的调节;KEGG的通路富集分析结果显示,丝裂原活化蛋白激酶(mitogen- activated protein kinase,MAPK)通路、晚期糖基化终末产物(advanced glycation end product,AGE)- AGE受体(receptor for AGE,RAGE)通路、TNF通路的差异蛋白表达水平较高。结论 桃红四物汤可能是通过抗炎、提高免疫、调控激素、延缓细胞凋亡等作用多靶点、多通路调控腰椎间盘突出症。 相似文献
BackgroundFor persons with adult congenital heart disease (ACHD), optimum patient selection and eligibility for orthotopic heart transplant (OHT) is not well defined. There is difficulty quantifying risk in patients with ACHD, leading to variability in OHT listing time and status. They are often disadvantaged due to a lack of mechanical support options, a shortage of congenital surgeons, and encounters with risk adverse health care programs. We examined patient characteristics and outcomes of a contemporary cohort of patients with ACHD undergoing OHT at a single high-volume Adult Congenital Heart Association accredited transplant center.MethodsRetrospective analysis of 49 consecutive patients with ACHD who underwent OHT from November 2010 through March 2020 was performed. Survival analysis was performed using Kaplan-Meier analysis.ResultsSurvival at 1 month, 1 year, 3 years, and 10 years was 94%, 92%, 92%, and 83%, respectively.ConclusionsThis study highlights the diversity and complexity of the population with ACHD proceeding to OHT as well as the multispecialty care needed to overcome disadvantages and optimize survival. Continued national discussions and policy adjustments will be necessary to bring parity and equity to this unique population. 相似文献
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe autoimmune disease that is commonly accompanied by cognitive impairment and various neurological and psychiatric symptoms, advanced image analyses help explore the pathogenesis of this disease. Therefore, this study aimed to explore specific structural and functional alterations and their relationship with the clinical symptoms of anti-NMDAR encephalitis. In this study, twenty-two patients with anti-NMDAR encephalitis after the acute stage and 29 controls received cognitive assessments and magnetic resonance imaging. Grey matter atrophy was measured using voxel-based morphometry, and functional alterations in abnormal regions were subsequently investigated using resting state functional connectivity (RSFC). Finally, correlation analyses were performed to explore the associations between imaging alterations and cognitive assessments. The patients demonstrated significant gray matter atrophy in the bilateral triangle part of the inferior frontal gyrus (triIFG.L and triIFG.R) and right precuneus, decreased RSFC between triIFG.L and bilateral Heschl gyrus (HES), decreased RSFC between triIFG.R and HES.R, decreased RSFC between right precuneus and left cerebellum, and increased RSFC between triIFG.R and left superior frontal gyrus. Further correlation analyses showed that the gray matter volume in triIFG.R and decreased RSFC between triIFG.L and HES.R were associated with decreased memory scores, whereas decreased RSFC between triIFG.R and HES.R was marginally correlated with the disease course in patients. In conclusion, this study suggests that cognitive impairments in patients with anti-NMDAR encephalitis may be mainly associated with gray matter atrophy and abnormal RSFC in the triIFG. These findings provide new insights into anti-NMDAR encephalitis pathogenesis and help explore potential treatments.