Treatment of diabetic kidney disease of stage Ⅲ-Ⅳ with Yiqi Wenyang Huoxue therapy: A meta-analysis

Objective: To systematically evaluate the effect of Yiqi Wenyang Huoxue therapy in treating diabetic kidney disease(DKD) of stage Ⅲ-Ⅳ. Method: The relevant literature was retrieved by computer from CNKI, Wanfang and VIP databases,CBM,PubMed,EMBase,Cochrane Library and Web of Science. Articles screening and data extraction were performed by two researchers separately and independently. The Meta-analysis was conducted with RevMan 5.3. Results: A total of 10 randomized controlled trials were collected,including 778 cases with DKD. Meta-analysis showed that the Yiqi Wenyang Huoxue Method combined with western medicine basic treatment could reduce 24hUTP[MD=-0.36, 95％CI (-0.46, -0.26), P <0.00001], UAER[MD=-36.72,95％CI (-47.21, -26.23), P<0.00001], Scr[MD= -16.28, 95％CI(-20.59,-11.97),P<0.00001],BUN[MD=-1.45,95％CI(-1.76,-1.14), P <0.00001], TC[MD=-0.64, 95％CI(-1.07,-0.21), P=0.004].There was also a reduction in HbA1c[MD=-0.50,95％CI (-0.94, -0.05),P =0.03], but the difference is not significant. Conclusion: Based on the current evidence, for the treatment of DKD of stage Ⅲ-IV, basic western medicine treatment combined with Yiqi Wenyang Huoxue method may better reduce urine protein, total cholesterol levels and improve renal function. The conclusion of this study needs to be further researched by high-quality studies, because that the quality of the included studies is generally low.     

Single-copy Loss of Rho Guanine Nucleotide Exchange Factor 10 (arhgef10) Causes Locomotor Abnormalities in Zebrafish Larvae

Objective To determine if ARHGEF10 has a haploinsufficient effect and provide evidence to evaluate the severity,if any,during prenatal consultation.Methods Zebrafish was used as a model for generating mutant.The pattern of arhgef10 expression in the early stages of zebrafish development was observed using whole-mount in situ hybridization(WISH).CRISPR/Cas9 was applied to generate a zebrafish model with a single-copy or homozygous arhgef10 deletion.Activity and light/dark tests were performed in arhgef10^?/?,arhgef10^+/?,and wild-type zebrafish larvae.ARHGEF10 was knocked down using small interferon RNA(siRNA)in the SH-SY5Y cell line,and cell proliferation and apoptosis were determined using the CCK-8 assay and Annexin V/PI staining,respectively.Results WISH showed that during zebrafish embryonic development arhgef10 was expressed in the midbrain and hindbrain at 36-72 h post-fertilization(hpf)and in the hemopoietic system at 36-48 hpf.The zebrafish larvae with single-copy and homozygous arhgef10 deletions had lower exercise capacity and poorer responses to environmental changes compared to wild-type zebrafish larvae.Moreover,arhgef10^?/? zebrafish had more severe symptoms than arhgef10^+/- zebrafish.Knockdown of ARHGEF10 in human neuroblastoma cells led to decreased cell proliferation and increased cell apoptosis.Conclusion Based on our findings,ARHGEF10 appeared to have a haploinsufficiency effect.     

Neonatal Exposure to Propofol Interferes with the Proliferation and Differentiation of Hippocampal Neural Stem Cells and the Neurocognitive Function of Rats in Adulthood via the Akt/p27 Signaling Pathway

Objective Neonatal exposure to propofol has been reported to cause neurotoxicity and neurocognitive decline in adulthood; however, the underlying mechanism has not been established.Methods SD rats were exposed to propofol on postnatal day 7(PND-7). Double-immunofluorescence staining was used to assess neurogenesis in the hippocampal dentate gyrus(DG). The expression of pAkt and p27 were measured by western blotting. The Morris water maze, novel object recognition test,and object location test we...     

针刺疗法治疗良性前列腺增生效果的Meta分析

背景 随着现代生活方式的改变及社会老龄化的加剧,良性前列腺增生（BPH）的发病率逐年增高,已成为威胁中老年男性健康的主要问题,目前西医多以手术及口服药物治疗,存在一定的不良反应及并发症,而临床应用毫针针刺治疗BPH疗效显著,但缺乏循证依据。 目的 系统评价针刺疗法治疗BPH的临床疗效。 方法 计算机检索中国知网、维普网、万方数据知识服务平台、中国生物医学文献服务系统、PubMed、Cochrane Library数据库,搜集关于针刺疗法治疗BPH的随机对照试验（RCT）：试验组为针刺疗法,配合或不配合对照组所用药物;对照组为常规西药治疗。检索时间为建库至2021-10-01。由2名研究者依据纳入与排除标准,独立筛选文献,提取评估,采用RevMan 5.3软件进行Meta分析。 结果 共纳入17篇文献,1 547例患者。Meta分析结果显示,试验组临床有效率、最大尿流率（Qmax）高于对照组〔OR=3.21,95%CI（2.25,4.57）,P<0.000 01;MD=2.48,95%CI（1.26,3.70）,P<0.000 01〕;试验组国际前列腺症状评分（IPSS）、残余尿量（PVR）、前列腺体积（PV）、生活质量指数评分（QOL）低于对照组〔MD=-2.39,95%CI（-3.84,-0.94）,P=0.001;MD=-10.59,95%CI（-15.20,-5.98）,P<0.000 01;MD=-3.50,95%CI（-5.07,-1.93）,P<0.000 1;MD=-0.68,95%CI（-0.99,-0.37）,P<0.000 1〕。单纯针刺疗法治疗BPH的临床有效率、Qmax高于常规西药治疗〔OR=3.53,95%CI（2.20,5.68）,P<0.000 01;MD=2.75,95%CI（1.62,3.88）,P<0.000 01〕;单纯针刺疗法治疗BPH的PVR、PV、QOL低于常规西药治疗〔MD=-9.41,95%CI（-15.87,-2.94）,P=0.004;MD=-2.99,95%CI（-4.86,-1.12）,P=0.002;MD=-0.74,95%CI（-1.33,-0.15）,P=0.01〕。针刺疗法+常规西药治疗BPH的临床有效率高于常规西药治疗〔OR=2.84,95%CI（1.67,4.82）,P=0.000 1〕;针刺疗法+常规西药治疗BPH的IPSS、PVR、PV、QOL低于常规西药治疗〔MD=-2.88,95%CI（-3.43,-2.32）,P<0.000 01;MD=-12.25,95%CI（-16.92,-7.57）,P<0.000 01;MD=-4.41,95%CI（-8.03,-0.79）,P=0.02;MD=-0.59,95%CI（-1.03,-0.15）,P=0.008〕。两组均无明显不良反应发生。对IPSS、Qmax、PVR、PV、QOL 5个结局指标分别进行敏感性分析,发现改变效应模型对合并结果影响不明显。对临床有效率、IPSS、Qmax、PVR、QOL的RCT进行漏斗图分析,结果显示,临床有效率的漏斗图双侧基本对称;IPSS、Qmax、PVR、QOL的漏斗图较为分散,存在发表偏倚。 结论 基于当前临床证据,针刺疗法治疗BPH的临床有效率和Qmax高于对照组,IPSS、PVR、PV、QOL低于对照组。因IPSS、Qmax、PVR、QOL的漏斗图提示存在发表偏倚,本研究的结果还需进一步验证。     

Novel effect of mineralocorticoid receptor antagonism to reduce proinflammatory cytokines and hypothalamic activation in rats with ischemia-induced heart failure

Blocking brain mineralocorticoid receptors (MRs) reduces the high circulating levels of tumor necrosis factor (TNF)-alpha in heart failure (HF) rats. TNF-alpha and other proinflammatory cytokines activate neurons in the paraventricular nucleus (PVN) of hypothalamus, including corticotropin-releasing hormone (CRH) neurons, by inducing cyclooxygenase (COX)-2 activity and synthesis of prostaglandin E2 by perivascular cells of the cerebral vasculature. We tested the hypothesis that systemic treatment with a MR antagonist would reduce hypothalamic COX-2 expression and PVN neuronal activation in HF rats. Rats underwent coronary ligation to induce HF, confirmed by echocardiography, or sham surgery, followed by 6 weeks treatment with eplerenone (30 mg/kg per day, orally) or vehicle (drinking water). Eplerenone-treated HF rats had lower plasma TNF-alpha, interleukin (IL)-1beta and IL-6, less COX-2 staining of small blood vessels penetrating PVN, fewer PVN neurons expressing Fra-like activity (indicating chronic neuronal activation), and fewer PVN neurons staining for TNF-alpha, IL-1beta, and CRH than vehicle-treated HF rats. COX-2 and CRH protein expression in hypothalamus were 1.7- and 1.9-fold higher, respectively, in HF+vehicle versus sham+vehicle rats; these increases were attenuated (26% and 25%, respectively) in HF+eplerenone rats. Eplerenone-treated HF rats had less prostaglandin E2 in cerebrospinal fluid, lower plasma norepinephrine levels, lower left ventricular end-diastolic pressure, and lower right ventricle/body weight and lung/body weight ratios, but no improvement in left ventricular function. Treatment of HF rats with anticytokine agents, etanercept or pentoxifylline, produced very similar results. This study reveals a previously unrecognized effect of MR antagonism to minimize cytokine-induced central neural excitation in rats with HF.     

Plasma asymmetric dimethylarginine concentrations in newly diagnosed patients with acute myocardial infarction or unstable angina pectoris during two weeks of medical treatment

A high concentration of plasma asymmetric dimethylarginine (ADMA) has been associated with several risk factors for atherosclerosis, and this may increase the risk for acute coronary syndromes (ACSs). We measured plasma ADMA concentrations in patients who had newly diagnosed ACS (n = 48), and we followed the changes in ADMA concentrations during these patients' short-term medical therapy, which included various combination of drugs with or without percutaneous coronary interventions according to the needs of each patient. Concentrations of plasma ADMA were found to be high in patients who had ACS compared with 48 age-matched healthy control subjects (3.13 +/- 0.85 vs 1.57 +/- 0.85 mumol/L, p <0.0001). Follow-up measurements of ADMA showed dramatic decreases in plasma ADMA concentrations over 2 weeks of medical therapy for ACS (from 3.27 +/- 0.87 to 1.52 +/- 0.47 mumol/L, p <0.0001). Plasma ADMA at baseline showed a significant positive correlation with serum C-reactive protein and plasma insulin and a significant negative correlation with serum levels of high-density lipoprotein and plasma alpha-tocopherol. During therapy, changes in plasma ADMA concentrations were significantly correlated with changes in the ratio of total cholesterol to high-density lipoprotein cholesterol and in serum C-reactive protein concentrations but not with changes in insulin levels. This study provides the first evidence that plasma ADMA concentrations are significantly high in patients who have ACS and that ADMA concentrations rapidly decrease after short-term medical therapy.     

Antisense oligonucleotide reduction of DGAT2 expression improves hepatic steatosis and hyperlipidemia in obese mice

In this study, we investigated the role of acyl-coenzyme A:diacylglycerol acyltransferase 2 (DGAT2) in glucose and lipid metabolism in obese mice by reducing its expression in liver and fat with an optimized antisense oligonucleotide (ASO). High-fat diet-induced obese (DIO) C57BL/6J mice and ob/ob mice were treated with DGAT2 ASO, control ASO, or saline. DGAT2 ASO treatment reduced DGAT2 messenger RNA (mRNA) levels by more than 75% in both liver and fat but did not change DGAT1 mRNA levels in either of these tissues, which resulted in decreased DGAT activity in liver but not in fat. DGAT2 ASO treatment did not cause significant changes in body weight, adiposity, metabolic rate, insulin sensitivity, or skin microstructure. However, DGAT2 ASO treatment caused a marked reduction in hepatic triglyceride content and improved hepatic steatosis in both models, which was consistent with a dramatic decrease in triglyceride synthesis and an increase in fatty acid oxidation observed in primary mouse hepatocytes treated with DGAT2 ASO. In addition, the treatment lowered hepatic triglyceride secretion rate and plasma triglyceride levels, and improved plasma lipoprotein profile in DIO mice. The positive effects of the DGAT2 ASO were accompanied by a reduction in the mRNA levels of several hepatic lipogenic genes, including SCD1, FAS, ACC1, ACC2, ATP-citrate lyase, glycerol kinase, and HMG-CoA reductase. In conclusion, reduction of DGAT2 expression in obese animals can reduce hepatic lipogenesis and hepatic steatosis as well as attenuate hyperlipidemia, thereby leading to an improvement in metabolic syndrome.     

Assessment of health-related quality of life in Chinese patients with minimal hepatic encephalopathy

AIM:To evaluate the health-related quality of life (HRQOL) based on the Chinese version of SF-36 and Chronic Liver Disease Questionnaire (CLDQ) in subjects with chronic hepatitis B,liver cirrhosis,including patients with minimal hepatic encephalopathy (MHE). METHODS:The SF-36 and CLDQ were administered to 160 healthy volunteers,20 subjects with chronic hepatitis B and 106 patients with cirrhosis (33 cases exhibited MHE). HRQOL scores were compared among the different study groups. The SF-36 includes eight health concepts:physical functioning,role-physical,body pain,general health,vitality,social functioning,role-emotion,and mental health. Six domains of CLDQ were assessed:abdominal symptoms,fatigue,systemic symptoms,activity,emotional function and worry. RESULTS:Compared with healthy controls (96.9 ± 4.5,86.6 ± 18.4,90.1 ± 12.5,89.0 ± 5.7,87.5 ± 4.3,95.8 ± 7.1,88.5 ± 15.9,88.7 ± 5.2 in SF-36 and 6.7 ± 0.5,6.1 ± 0.6,6.3 ± 0.6,6.5 ± 0.5,6.3 ± 0.5,6.8 ± 0.4 in CLDQ),patients with chronic hepatitis B (86.3 ± 11.0,68.8 ± 21.3,78.9 ± 14.4,60.8 ± 10.5,70.8 ± 8.6,76.1 ± 12.6,50.0 ± 22.9,72.2 ± 10.6 and 5.5 ± 1.0,4.5 ± 1.0,5.2 ± 1.1,5.3 ± 0.9,4.8 ± 0.9,4.9 ± 1.0) and cirrhosis (52.8 ± 17.4,32.8 ± 27.9,61.6 ± 18.9,30.2 ± 18.3,47.9 ± 20.1,54.0 ± 19.2,28.9 ± 26.1,51.1 ± 17.8 and 4.7 ± 1.2,3.9 ± 1.2,4.7 ± 1.2,4.7 ± 1.3,4.7 ± 1.0,4.4 ± 1.1) had lower HRQOL on all scales of the SF-36 and CLDQ (P < 0.01 for all). Increasing severity of liver cirrhosis (based on the Child-Pugh score/presence or absence of MHE) was associated with a decrease in most components of SF-36 and CLDQ,especially SF-36.CONCLUSION:The Chinese version of SF-36 along with CLDQ is a valid and reliable method for testing MHE in patients with liver cirrhosis. Cirrhosis and MHE are associated with decreased HRQOL.     

Outcomes of patients with Kaposi's sarcoma who start antiretroviral therapy under routine programme conditions in Malawi

AIDS-associated Kaposi's sarcoma (KS) is the most common AIDS-related malignancy in sub-Saharan Africa, with a generally unfavourable prognosis. We report on six-month and 12-month cohort treatment outcomes of human immunodeficiency virus (HIV)-positive KS patients and HIV-positive non-KS patients treated with antiretroviral therapy (ART) in public sector facilities in Malawi. Data were collected from standardized antiretroviral (ARV) patient master cards and ARV patient registers. Between July and September 2005, 7905 patients started ART-488 (6%) with a diagnosis of KS and 7417 with a non-KS diagnosis. Between January and March 2005, 4580 patients started ART-326 (7%) with a diagnosis of KS and 4254 with a non-KS diagnosis. At six-months and 12-months, significantly fewer KS patients were alive and significantly more had died or defaulted compared to non-KS patients. HIV-positive KS patients on ART in Malawi have worse outcomes than other patients on ART. Methods designed to improve these outcomes must be found.