Hyodeoxycholic acid protects the neurovascular unit against oxygen-glucose deprivation and reoxygenation-induced injury in vitro

Calculus bovis is commonly used for the treatment of stroke in traditional Chinese medicine. Hyodeoxycholic acid(HDCA) is a bioactive compound extracted from calculus bovis. When combined with cholic acid, baicalin and jas-minoidin, HDCA prevents hypoxia-reoxygenation-induced brain injury by suppressing endoplasmic reticulum stress-mediated apoptotic signaling. However, the effects of HDCA in ischemic stroke injury have not yet been studied. Neurovascular unit(NVU) dysfunction occurs in ischemic stroke. Therefore, in this study, we investigated the effects of HDCA on the NVU under ischemic conditions in vitro. We co-cultured primary brain microvascular endothelial cells, neurons and astrocytes using a transwell chamber co-culture system. The NVU was pre-treated with 10.16 or 2.54 μg/mL HDCA for 24 hours before exposure to oxygen-glucose deprivation for 1 hour. The cell counting kit-8 assay was used to detect cell activity. Flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling were used to assess apoptosis. Enzyme-linked immunosorbent assay was used to measure the expression levels of inflammatory cytokines, including interleukin-1β, interleukin-6 and tumor necrosis factor-α, and neurotrophic factors, including brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. Oxidative stress-related factors, such as superoxide dismutase, nitric oxide, malondialdehyde and γ-glutamyltransferase, were measured using kits. Pretreatment with HDCA significantly decreased blood-brain barrier permeability and neuronal apoptosis, significantly increased transendothelial electrical resistance and γ-glutamyltransferase activity, attenuated oxidative stress damage and the release of inflammatory cytokines, and increased brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor expression. Our findings suggest that HDCA maintains NVU morphological integrity and function by modulating inflammation, oxidation stress, apoptosis, and the expression of neurotrophic factors. Therefore, HDCA may have therapeutic potential in the clinical management of ischemic stroke. This study was approved by the Ethics Committee of Experimental Animals of Beijing University of Chinese Medicine(approval No. BUCM-3-2016040201-2003) in April 2016.     

电针复合TCI靶控输注在单肺通气食管癌开胸手术麻醉中的应用与安全性＊

目的 探讨电针复合靶控输注（Target Controlled Infusion， TCI）在单肺通气食管癌开胸手术麻醉中的应用价值。方法 选取于我院拟行单肺通气食管癌开胸切除手术患者60例作为研究对象。随机将其分为试验组与对照组，对照组30例采取气管插管全麻及TCI靶控输注维持麻醉深度，试验组30例则在对照组方案基础上辅助电针麻醉，记录两组患者手术麻醉时间、药物用量、苏醒时间、并发症；以及术前（T_Ⅰ）、插管前即刻（T_Ⅱ）、插管后1 min（T_Ⅲ）、切皮即刻（T_Ⅳ）、去骨时（T_Ⅴ）、拔管即刻（T_Ⅵ）时平均动脉压（MAP）、平均心率（HR）、BIS值；术前、术后1天、术后3天简易智能精神状态检查量表（MMSE）；并于麻醉诱导前（T₀）、手术开始2 h（T₁）、术后1天（T₂）、术后3天（T₃）时抽取患者外周静脉血检测IL-1β、IL-6、IL-10、TNF-α浓度。结果 试验组手术用时、麻醉时间略低于对照组，但差异无统计学意义（P>0.05），试验组异丙酚、舒芬太尼用量以及苏醒时间均明显低于对照组（P<0.05）；T_Ⅱ时两组平均动脉压（Mean Arterial Pressure， MAP）、心率（Heartrate， HR）较术前明显降低，且试验组MAP明显低于对照组（P<0.05），但两组T_Ⅱ时HR比较无显著差异（P>0.05）；T_Ⅲ、T_Ⅵ时对照组MAP、HR明显高于T_Ⅰ时，而试验组MAP、HR与T_Ⅰ比较无显著差异（P>0.05）。术后1天、3天试验组简易智能精神状态检查量表（Mini-Mental State Examination， MMSE）评分低于对照组，有显著性差异（P<0.05）。T₁、T₂、T₃时试验组白介素-1β（IL-1β）、白介素-6（IL-6）、肿瘤坏死因子（Tumor Necrosis Factor-α， TNF-α）水平明显低于对照组（P<0.05），白介素-10（IL-10）水平明显高于对照组（P<0.05）。结论 采用电针复合TCI靶控输注麻醉方案可有效提升单肺通气食管癌开胸手术麻醉效果，能够降低患者术后认知功能障碍发生风险。     

Challenges facing HIV-positive persons who use drugs and their families in Vietnam

It is hypothesized that persons who use drugs (PWUD) in Vietnam who are also HIV-positive may face additional challenges in psychosocial outcomes, and these challenges may extend to their family members. In this study, we examined depressive symptoms, stigma, social support, and caregiver burden of HIV-positive PWUD and their family members, compared to the outcomes of HIV-negative PWUD and their family members. Baseline, 3-month, and 6-month assessment data were gathered from 83 PWUD and 83 family members recruited from four communes in Phú Th? Province, Vietnam. For PWUD, although we observed a general decline in overall stigma over time for both groups, HIV-positive PWUD consistently reported significantly higher overall stigma for all three periods. Depressive symptoms among family members in both groups declined over time; however, family members of HIV-positive PWUD reported higher depressive symptoms across all three periods. In addition, family members of HIV-positive PWUD reported lower levels of tangible support across all three periods. Caregiver burden among family members of HIV-positive PWUD increased significantly over time, whereas the reported burden among family members of HIV-negative PWUD remained relatively unchanged. The findings highlight the need for future interventions for PWUD and family members, with targeted and culturally specific strategies to focus on the importance of addressing additional stigma experienced by PWUD who are HIV-positive. Such challenges may have direct negative impact on their family members' depressive symptoms, tangible support, and caregiver burden.     

Clinical analysis of peritoneal dialysis in the treatment of rapidly progressive glomerulonephritis

Objective To observe the clinical characteristics and prognosis of patients with rapidly progressive glomerulonephritis (RPGN) caused by lupus nephritis, antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis, or primary glomerulonephritis who were treated with peritoneal dialysis (PD) and then withdrew PD because of renal recovery. Methods Data of the above patients were retrospectively analyzed. The patients were diagnosed as RPGN and received PD therapy in Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Zhejiang University from February 2009 to August 2018. The patients were divided into early withdrawal group (PD time≤183 days, n=24) and late withdrawal group (PD time＞183 day, n=24). The differences of clinical characteristics between the two groups were compared. The cumulative incidence of adverse events in both groups was analyzed using Kaplan-Meier curves. Cox proportional hazards model was used to analyze the risk factors influencing the prognosis of patients. Results Forty-eight RPGN patients were included. The median time of maintaining PD was 178(76, 378) days. Compared with the late withdrawal group, the patients in early withdrawal group had lower levels of urine volume, serum albumin and parathyroid hormone, and lower rates of gross hematuria and hypertension at the beginning of PD, and received higher rates of methylprednisolone impulse, combined immunosuppressive agents, and hemodialysis or continuous renal replacement therapy (all P＜0.05). At the time of PD withdrawal, the levels of serum creatinine, serum calcium, serum albumin and parathyroid hormone in the early withdrawal group were significantly lower than those in the late withdrawal group (all P＜0.05). The Kaplan-Meier curves showed that there was no significant difference in the cumulative survival of patients in both groups (log-rank test χ2=3.485, P=0.062). Cox regression analysis revealed serum creatinine≥209 μmol/L at the time of PD withdrawal was an independent risk factor for poor prognosis (HR=5.253，95%CI 1.757-15.702, P=0.003). Conclusions PD can be used for RPGN patients caused by lupus nephritis, ANCA-associated vasculitis and primary nephritis. Serum creatinine≥209 μmol/L at the time of PD withdrawal is an independent risk factor for poor prognosis.     

Application of the adverse outcome pathway framework to genotoxic modes of action

In May 2017, the Health and Environmental Sciences Institute's Genetic Toxicology Technical Committee hosted a workshop to discuss whether mode of action (MOA) investigation is enhanced through the application of the adverse outcome pathway (AOP) framework. As AOPs are a relatively new approach in genetic toxicology, this report describes how AOPs could be harnessed to advance MOA analysis of genotoxicity pathways using five example case studies. Each of these genetic toxicology AOPs proposed for further development includes the relevant molecular initiating events, key events, and adverse outcomes (AOs), identification and/or further development of the appropriate assays to link an agent to these events, and discussion regarding the biological plausibility of the proposed AOP. A key difference between these proposed genetic toxicology AOPs versus traditional AOPs is that the AO is a genetic toxicology endpoint of potential significance in risk characterization, in contrast to an adverse state of an organism or a population. The first two detailed case studies describe provisional AOPs for aurora kinase inhibition and tubulin binding, leading to the common AO of aneuploidy. The remaining three case studies highlight provisional AOPs that lead to chromosome breakage or mutation via indirect DNA interaction (inhibition of topoisomerase II, production of cellular reactive oxygen species, and inhibition of DNA synthesis). These case studies serve as starting points for genotoxicity AOPs that could ultimately be published and utilized by the broader toxicology community and illustrate the practical considerations and evidence required to formalize such AOPs so that they may be applied to genetic toxicity evaluation schemes. Environ. Mol. Mutagen. 61:114–134, 2020. © 2019 Wiley Periodicals, Inc.