Mechanism of action of Orthosiphon stamineus against non-alcoholic fatty liver disease: Insights from systems pharmacology and molecular docking approaches

Non-alcoholic fatty liver disease (NAFLD) is one of the most common complications of a metabolic syndrome caused by excessive accumulation of fat in the liver. Orthosiphon stamineus also known as Orthosiphon aristatus is a medicinal plant with possible potential beneficial effects on various metabolic disorders. This study aims to investigate the in vitro inhibitory effects of O. stamineus on hepatic fat accumulation and to further use the computational systems pharmacology approach to identify the pharmacokinetic properties of the bioactive compounds of O. stamineus and to predict their molecular mechanisms against NAFLD. Methods: The effects of an ethanolic extract of O. stamineus leaves on cytotoxicity, fat accumulation and antioxidant activity were assessed using HepG2 cells. The bioactive compounds of O. stamineus were identified using LC/MS and two bioinformatics databases, namely the Traditional Chinese Medicine Integrated Database (TCMID) and the Bioinformatics Analysis Tool for the Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM). Pathway enrichment analysis was performed on the predicted targets of the bioactive compounds to provide a systematic overview of the molecular mechanism of action, while molecular docking was used to validate the predicted targets. Results: A total of 27 bioactive compounds corresponding to 50 potential NAFLD-related targets were identified. O. stamineus exerts its anti-NAFLD effects by modulating a variety of cellular processes, including oxidative stress, mitochondrial β-oxidation, inflammatory signalling pathways, insulin signalling, and fatty acid homeostasis pathways. O. stamineus is significantly targeting many oxidative stress regulators, including JNK, mammalian target of rapamycin (mTOR), NFKB1, PPAR, and AKT1. Molecular docking analysis confirmed the expected high affinity for the potential targets, while the in vitro assay indicates the ability of O. stamineus to inhibit hepatic fat accumulation. Conclusion: Using the computational systems pharmacology approach, the potentially beneficial effect of O. stamineus in NAFLD was indicated through the combination of multiple compounds, multiple targets, and multicellular components.     

Effectiveness and safety of extracorporeal shock wave treatment for low back pain：a systematic review and meta-analysis of RCTs

This meta-analysis was designed to assess the effectiveness and safety of extracorporeal shock wave therapy (ESWT) for patients with low back pain (LBP). Pubmed, Embase, Cochrane's library, PEDro (Physiotherapy Evidence Database), China National Knowledge Infrastructure (CNKI), and Wanfang Data were searched until December 2019 to identify studies assessing the effectiveness and safety of EPSW for LBP. The prime outcome is pain intensity measured by Visual Analog Scale (VAS) or numeric rating scale (NRS). Other outcomes included functional status, quality of life, psychological outcomes measured by Oswestry Disability Index (ODI), as well as the adverse events. Mean differences (MD) were calculated for continuous outcomes, while odd ratios (OR) were calculated for binary outcomes. Revman 5.3 software was used for statistical analysis. Five randomized controlled trials (RCTs) were finally included in this meta-analysis. The pooled mean difference in post-treatment pain scores was −2.37 (P ＜0.0001), indicating that post-treatment pain scores was significantly higher by 2.37 in control group than in ESWT group. At a mean follow-up time of 4–6 weeks, the pooled mean difference in ODI scores was −14.10 (P ＜0.00001), indicating that the pooled mean difference of post-treatment ODI scores was 14.10 higher in control group than in ESWT group. The use of ESWT is effective in alleviating pain and improving the general functional state for patients with LBP. However, more evidence was needed to verify its safety.     

Whose place? Lessons from a case study of a guardianship determination for an Australian Indigenous child

Whose values matter when considering which environment is healthier for a child whose guardianship is contested? The biological mother from a remote Australian Aboriginal community, who voluntarily relinquished her but has now requested her return? The foster mother who has cared for her in a metropolitan centre in another State of Australia, thousands of kilometres away? The welfare professionals who also live in that city? Or the child herself, who left her birth home and community five years earlier at the age of two? Drawing on a case study of a seven-year old Aboriginal girl, the authors argue that non-Indigenous values trumped Indigenous values without the realisation of key players who were empowered to make such determinations. The article uses Manuel DeLanda's neo-assemblage theory to consider the range of processes that exert themselves to shape place-values and social identity in colonised nations. It will also draw on Erik Erikson's and Lev Vygotsky's theories of psychosocial development to consider competing sets of values that raised feelings of dissonance within the child. Beliefs about what makes a place health-giving are revealed to be complex in colonised nations. Despite policy and legislative changes to better support Aboriginal people and their right to difference, non-Indigenous professionals can continue to be driven by an unrecognised systemic racism. While place-values are not, of course, the only (or perhaps even the most significant) consideration in guardianship determinations, this article will argue they can play a significant and covert role.     

脑出血继发损伤中沉默信息调节因子2的表达和炎症反应*

目的：探讨脑出血对酵母沉默信息调节因子2（Sirt2）和炎症的影响。方法：将胶原酶Ⅳ注入SD大鼠右侧 纹状体中建立脑出血模型，通过免疫印迹和ELISA 等方法测定大鼠脑出血后48 h 的Sirt2 的表达及炎症变化。利 用Hemin 诱导PC12 细胞损伤模拟体外脑出血模型，并检测Sirt2 及炎症变化；采用短发夹RNA（shRNA）-Sirt2 沉 默Sirt2 在PC12 细胞中的表达及对炎症的影响。结果：手术后48 h 脑出血行为学评分最低。脑出血组Sirt2 的表达 显著高于假手术组。脑出血组IL-6、IL-1β 表达显著升高。结论：脑出血可以促进Sirt2 的表达和炎症反应，降低 Sirt2 的表达可减缓炎症反应。 关键词 脑出血；沉默信息调节     

何首乌致药物性肝损伤的病理学特点

目的了解何首乌致药物性肝损伤(Polygonum multiflorum-associated drug induce liver injury,PM-DILI)的临床病理学特点。方法收集2019年3月1日至2021年3月1日深圳市第三人民医院收治的8例PM-DILI患者临床资料。肝穿组织进行苏木素-伊红染色、网状纤维染色、Masson三色染色、铁、铜特殊染色和免疫组织化学染色,显微镜下观察分析。结果8例PM-DILI患者男女比为1∶1,平均年龄43岁,其中6例为急性PM-DILI,2例慢性为PM-DILI。入院血清学检查异常主要包括转氨酶升高和淤胆均为7例。主要组织病理学改变为点灶状坏死8例、界面炎5例、融合坏死4例,融合坏死以肝腺泡3带为主,不伴或伴少数炎细胞浸润;胆汁淤积5例,为肝腺泡3带的肝细胞、毛细胆管内淤胆,不伴或伴少数炎细胞浸润;中央静脉炎3例;病程长者可发生肝纤维化,甚至肝硬化2例。结论肝腺泡3带为主的急性淤胆和肝细胞坏死是PM-DILI主要组织学表现,严重者可发生静脉炎等血管损伤。     

Priorities for content for a short-course on postoperative care relevant for low- and middle-income countries: an e-Delphi process with training facilitators

Most surgical and anaesthetic mortality and morbidity occurs postoperatively, disproportionately affecting low- and middle-income countries. Various short courses have been developed to improve patient outcomes in low- and middle-income countries, but none specifically to address postoperative care and complications. We aimed to identify key features of a proposed short-course addressing this topic using a Delphi process with low- and middle-income country anaesthesia providers trained as short-course facilitators. An initial questionnaire was co-developed from literature review and exploratory workshops to include 108 potential course features. Features included content; teaching method; appropriate participants; and appropriate faculty. Over three Delphi rounds (panellists numbered 86, 64 and 35 in successive cycles), panellists indicated which features they considered most important. Responses were analysed by geographical regions: Africa, the Americas, south-east Asia and Western Pacific. Ultimately, panellists identified 60, 40 and 54 core features for the proposed course in each region, respectively. There were high levels of consensus within regions on what constituted core course content, but not between regions. All panellists preferred the small group workshop teaching method irrespective of region. All regions considered anaesthetists to be key facilitators, while all agreed that both anaesthetists and operating theatre nurses were key participants. The African and Americas regional panels recommended more multidisciplinary healthcare professionals for participant roles. Faculty from high-income countries were not considered high priority. Our study highlights variability between geographical regions as to which course features were perceived as most locally relevant, supporting regional adaptation of short-course design rather than a one-size-fits-all model.