基于网络药理学和分子对接技术研究黄芪-赤芍治疗COPD的作用机制＊

目的 基于网络药理学和分子对接技术探究黄芪-赤芍配伍对治疗慢性阻塞性肺疾病（chronic obstructive pulmonary disease，COPD）的作用机制。方法 利用TCMSP，Pharmmaper数据库，筛选黄芪-赤芍治疗COPD的活性成分和潜在靶点；结合Genecards数据库挖掘的COPD相关靶点，对黄芪-赤芍药对与COPD靶点进行PPI网络构建，交互处理得到黄芪-赤芍药对治疗COPD的关键靶点，并进行GO分析和KEGG通路富集分析；并采用分子对接技术将主要活性成分与TNF-α（肿瘤坏死因子），IL-6（白细胞介素6）等进行分子对接；最后利用A549炎症细胞与人脐静脉内皮细胞缺氧损伤模型进行体外细胞实验对结果加以验证。结果 黄芪-赤芍药对中44个有效成分作用于COPD，核心成分为：槲皮素、山奈酚、丁子香萜、芍药苷、（2R，3R）-4-methoxyl-distylin、二氢异黄酮；黄芪-赤芍药对通过IL6、PTGS2、TNF等113个靶蛋白，调控Ras、PI3KAkt、IL-17等多条信号通路治疗COPD，且分子对接结果显示槲皮素、山奈酚、丁子香萜、芍药苷与IL-6、PTGS2、TNF大分子蛋白有良好的结合性，体外细胞试验证实，槲皮素与山奈酚均能减少IL-8，MMP-9炎症因子的分泌，具有不同程度的抗炎效果；芍药苷有明显的扩血管、抗血栓之效。结论 黄芪-赤芍药对治疗COPD具有多成分、多靶点、多通路、整体调节的作用特点。初步揭示了黄芪-赤芍药对通过抑制炎症反应、调节上皮细胞生长增强保护屏障等预测出黄芪-赤芍药对治疗COPD的潜在作用机制，以期为其活性成分的药效物质基础提供理论研究和思路。     

Hip Displacement in Cerebral Palsy: The Role of Surveillance

IntroductionHip displacement is common in cerebral palsy (CP) and is related to the severity of neurological and functional impairment. It is a silent, but progressive disease, and can result in significant morbidity and decreased quality of life, if left untreated. The pathophysiology of hip displacement in CP is a combination of hip flexor-adductor muscle spasticity, abductor muscle weakness, and delayed weight-bearing, resulting in proximal femoral deformities and progressive acetabular dysplasia. Due to a lack of symptoms in the early stages of hip displacement, the diagnosis is easily missed. Awareness of this condition and regular surveillance by clinical examination and serial radiographs of the hips are the key to early diagnosis and treatment.Hip surveillance programmesSeveral population-based studies from around the world have demonstrated that universal hip surveillance in children with CP allows early detection of hip displacement and appropriate early intervention, with a resultant decrease in painful dislocations. Global hip surveillance models are based upon the patients’ age, functional level determined by the Gross Motor Function Classification system (GMFCS), gait classification, standardized clinical exam, and radiographic indices such as the migration percentage (MP), as critical indicators of progressive hip displacement.ConclusionDespite 25 years of evidence showing the efficacy of established hip surveillance programmes, there is poor awareness among healthcare professionals in India about the importance of regular hip surveillance in children with CP. There is a need for professional organizations to develop evidence-based guidelines for hip surveillance which are relevant to the Indian context.     

Living with the financial consequences of cancer: A life course perspective

Abstract

Purpose

Financial hardship can be a major cause of distress among persons with cancer, resulting in chronic stress and impacting physical and emotional health. This paper provides an analysis of the lived experience of cancer patients’ financial hardship from diagnosis to post-treatment.