The protective role of tacrine and donepezil in the retina of acetylcholinesterase knockout mice

AIM:To determine the effect of different concentrations of the acetylcholinesterase (AChE) inhibitors tacrine and donepezil on retinal protection in AChE^+/- mice (AChE knockout mice) of various ages.METHODS:Cultured ARPE-19 cells were treated with hydrogen peroxide (H2O2) at concentrations of 0, 250, 500, 1000 and 2000 μmol/L and protein levels were measured using Western blot. Intraperitoneal injections of tacrine and donepezil (0.1 mg/mL, 0.2 mg/mL and 0.4 mg/mL) were respectively given to AChE^+/- mice aged 2mo and 4mo and wild-type S129 mice for 7d; phosphate buffered saline (PBS) was administered to the control group. The mice were sacrificed after 30d by in vitro cardiac perfusion and retinal samples were taken. AChE-deficient mice were identified by polymerase chain reaction (PCR) analysis using specific genotyping protocols obtained from the Jackson Laboratory website. H&E staining, immunofluorescence and Western blot were performed to observe AChE protein expression changes in the retinal pigment epithelial (RPE) cell layer.RESULTS:Different concentrations of H2O2 induced AChE expression during RPE cell apoptosis. AChE^+/- mice retina were thinner than those in wild-type mice (P<0.05); the retinal structure was still intact at 2mo but became thinner with increasing age (P<0.05); furthermore, AChE^+/- mice developed more slowly than wild-type mice (P<0.05). Increased concentrations of tacrine and donepezil did not significantly improve the protection of the retina function and morphology (P>0.05).CONCLUSION:In vivo, tacrine and donepezil can inhibit the expression of AChE; the decrease of AChE expression in the retina is beneficial for the development of the retina.     

Association of weight-adjusted-waist index with all-cause and cardiovascular mortality in China: A prospective cohort study

Background and aimsAs a new simple anthropometric index, the weight-adjusted-waist index (WWI) appears to be superior to body mass index (BMI) and waist circumference (WC) in assessing both muscle and fat mass. We aimed to explore the association of WWI with all-cause and cardiovascular mortality in southern China.Methods and resultsA total of 12,447 participants (mean age, 59.0 ± 13.3 years; 40.6% men) in Jiangxi Province from the China Hypertension Survey study were included. WWI was defined as WC divided by the square root of weight. The outcome was all-cause and cardiovascular mortality. During a median follow-up of 5.6 years, 838 all-cause deaths occurred, with 390 cardiovascular deaths. Overall, there was a nonlinear positive relationship of WWI with all-cause and cardiovascular mortality. Accordingly, compared with participants in quartiles 1–3 (<11.2 cm/√kg), a significant higher risk of all-cause mortality (HR: 1.36, 95% CI: 1.17, 1.58) and cardiovascular mortality (HR: 1.43, 95% CI: 1.15, 1.77) were found in quartile 4 (≥11.2 cm/√kg). Further adjustment for BMI and WC did not substantially alter the results. No significant interactions were found in any of the subgroups (sex, age, area, physical activity, current smoking, current alcohol drinking, hypertension, and stroke).ConclusionHigher WWI levels (≥11.2 cm/√kg) were associated with increased the risk of all-cause and cardiovascular mortality in southern China. These findings, if confirmed by further studies, suggested that WWI may serve as a simple and effective anthropometric index in clinical practice.     

Downregulation of lncRNA MEG3 is involved in Parkinson’s disease

Metabolic Brain Disease - Long non-coding RNA (lncRNA) MEG3 regulates human cancers, while its role in Parkinson’s disease (PD) is unknown. The present study explored the involvement of MEG3...     

急性胰腺炎诊治的新理念、新技术及临床面临的难点与困惑

急性胰腺炎（AP）是最常见的消化系统急腹症之一,其中约20%为重症急性胰腺炎（SAP）,病情凶险,治疗棘 手。按病程分期进行个体化治疗的治疗理念和多学科诊治（MDT）的治疗模式的应用,显著降低了SAP的病死率。重 视AP合并症和并发症的治疗,及时选择外科手术治疗,开展高质量的临床研究,将有益于降低病死率,改善患者预后。 关键词：急性胰腺炎;多学科诊治;合并症与并发症     

丹参酮ⅡA通过抑制HDAC3影响巨噬细胞极化的作用研究

目的探讨丹参酮ⅡA(TanⅡA)通过抑制组蛋白去乙酰化酶3(HDAC3)影响巨噬细胞极化的作用。方法应用中药系统药理学数据库与分析平台(TCMSP)筛选TanⅡA药效靶点和动脉粥样硬化作用靶点,并将二者的交集基因进行KEGG通路分析,采用Cytoscape 3.7.1软件对主要交集基因-信号通路进行可视化分析。选用THP-1单核细胞株经佛波醇12-十四酸酯13-乙酸酯(PMA)诱导为贴壁的巨噬细胞后,分为M0组、氧化型低密度脂蛋白(ox-LDL)组、TanⅡA+ox-LDL组及ox-LDL+HDAC3 siRNA组。采用流式细胞术、免疫荧光实验及qRT-PCR技术检测TanⅡA对ox-LDL诱导的巨噬细胞极化方向的改变及HDAC3 mRNA表达水平的变化。结果生物信息学分析得到TanⅡA药效靶点和动脉粥样硬化作用靶点有23个交集基因,选取排序靠前的20条信号通路进行可视化分析,发现主要富集于动脉粥样硬化、流体剪切力和TNF信号通路等。其中,JUN、FOS、RELA、NFKBIA四个交集基因参与巨噬细胞极化的信号通路调控。流式细胞术、免疫荧光实验及qRT-PCR结果显示ox-LDL可诱导M0巨噬细胞CCR7和CCL2表达显著升高;与ox-LDL组相比,TanⅡA预处理的M0巨噬细胞经ox-LDL诱导后HDAC3、CCR7及CCL2 mRNA表达均下降,和ox-LDL+HDAC3 siRNA组结果一致。结论 TanⅡA能有效地阻止ox-LDL诱导巨噬细胞往M1方向极化,其机制可能是通过调控巨噬细胞HDAC3表达介导的。     

Ras-MAPK通路在食管癌中的研究进展

Ras is best known for the ability of regulating cell growth, proliferation and differentiation. Mutations in Ras are associated with abnormal cell proliferation, resulting in the incidence of all human cancers. Mitogen-activated protein kinase (MAPK) signaling pathways are the most well described pathways in carcinogenesis, which has been identified as a key downstream effector in Ras signaling as well as playing important roles in prognosis of tumors. Recently, evidence has gradually accumulated to demonstrate that mutation in Ras or aberrant expression of MAPK has profound effects on the incidence of esophageal carcinoma, and applications of some chemotherapeutic drugs can not lead to the expectant function. Further understanding of the relevant molecular mechanisms of Ras-MAPK signaling pathways will be helpful for development of efficient targeting therapeutic approaches to the treatment of esophageal cancer. In this article, the advances of Ras-MAPK signaling pathways in esophageal carcinoma are reviewed.     

维持性血液透析患者丙型肝炎病毒感染危险因素分析

目的探讨维持性血液透析（MHD）患者丙型肝炎病毒（HCV）感染危险因素,为临床防控提供科学依据。方法收集2017年12月至2019年12月在南昌大学第一附属医院行维持性血液透析治疗达3个月以上患者392例为研究对象,收集患者一般资料、临床资料及实验室检测数据,透析前后对所有患者行丙型肝炎病毒抗体（抗-HCV）检测。比较受试者透析治疗后HCV感染阳性患者（阳性组）与HCV感染阴性组患者（阴性组）的相关资料,采用Logistic多因素回归分析分析维持性血液透析感染HCV的危险因素。结果 392例MHD患者透析治疗后HCV感染20例,丙型肝炎发生率为5.1%。Logistic多因素回归分析显示,透析时间长、输血次数多、频繁异地透析、肾移植史等因素是HCV感染的危险因素。结论血液透析是丙型肝炎病毒感染的高危人群,丙型肝炎病毒感染与输血次数、透析时间长短及频次、肾移植史等因素密切相关。严格按照《血液净化标准操作规程》认真操作,可明显减少医源性HCV交叉感染的发生。     

缬沙坦氨氯地平片在中国健康人体内的生物等效性研究

目的 评价缬沙坦氨氯地平片受试制剂与参比制剂在中国健康人体内的生物等效性和观察两制剂的安全性。方法 采用单中心、随机、开放、3周期、部分重复交叉设计。受试者经高脂高热餐后/空腹单剂量口服缬沙坦氨氯地平片受试制剂或参比制剂,采血至给药后72 h,周期间的清洗期为14 d。采用经方法学验证的LC-MS/MS检测血浆中缬沙坦和氨氯地平的浓度。选择Phoenix WinNonlin 软件(8.0版本),以非房室模型(non-compartmental analysis,NCA)计算缬沙坦、氨氯地平的药动学参数。采用参比制剂校正的平均生物等效性(reference-scaled average bioequivalence,RSABE)和平均生物等效性(average bioequivalence,ABE)方法评价缬沙坦的生物等效性,ABE方法评价氨氯地平的生物等效性。结果 缬沙坦在空腹条件下的Cmax、AUC0-t和AUC0-∞和在餐后条件下的Cmax的个体内变异系数均>0.294,采用参比制剂标度的平均生物等效性方法。计算得到单侧95%置信上限<0和几何均值比估计值为80.00%~125.00%。缬沙坦餐后条件下的AUC0-t和AUC0-∞的个体内变异系数<0.294,采用平均生物等效性方法,受试制剂与参比制剂的AUC0-t、AUC0-∞经对数转换后的几何均值比值的90%置信区间均在80.00%~125.00%内。综上,两制剂中的缬沙坦具有生物等效性。氨氯地平的Cmax、AUC0-t和AUC0-∞的个体内变异系数<0.294,采用平均生物等效性方法,受试制剂与参比制剂的Cmax、AUC0-t和AUC0-∞经对数转换后的几何均值比值的90%置信区间均在80.00%~125.00%内,表明两制剂中的氨氯地平具有生物等效性。结论 缬沙坦氨氯地平片受试制剂和参比制剂在中国健康人体内具有生物等效性。     

Resuscitation therapy for traumatic brain injuryinduced coma in rats:mechanisms of median nerve electrical stimulation

In this study, rats were put into traumatic brain injury-induced coma and treated with median nerve electrical stimulation. We explored the wake-promoting effect, and possible mechanisms, of median nerve electrical stimulation. Electrical stimulation upregulated the expression levels of orexin-A and its receptor OX1 R in the rat prefrontal cortex. Orexin-A expression gradually increased with increasing stimulation, while OX1 R expression reached a peak at 12 hours and then decreased. In addition, after the OX1 R antagonist, SB334867, was injected into the brain of rats after traumatic brain injury, fewer rats were restored to consciousness, and orexin-A and OXIR expression in the prefrontal cortex was downregulated. Our findings indicate that median nerve electrical stimulation induced an up-regulation of orexin-A and OX1 R expression in the prefrontal cortex of traumatic brain injury-induced coma rats, which may be a potential mechanism involved in the wake-promoting effects of median nerve electrical stimulation.     

问号钩体56601株外分泌蛋白功能研究

目的探讨体内外差异表达的问号钩体56601株外分泌脂蛋白（LA₃469、LA₂413、LA₂823和LB₁94）的致病功能。方法利用体外重组表达技术,在体外表达、纯化四个外分泌脂蛋白。采用ELISA的方法,检测钩体外分泌脂蛋白与不同细胞外基质的黏附功能。结果 LA₃469与LA₂413能够与细胞外基质Laminin、Collagen I以及Collagen IV发生黏附作用,LA₃469还能够与Fibronectin发生黏附作用。结论结合前期的研究,提示问号钩体外分泌脂蛋白LA₃469可能是钩体致病过程中的一个重要的致病因子。