谷胱甘肽在肝脏疾病相关信号通路中的作用及研究进展

谷胱甘肽(GSH)是细胞内主要的抗氧剂和氧化还原、细胞信号调节器,它能还原过氧化氢、清除活性氧(ROS)和含氮自由基使细胞免受氧化应激损伤。不管细胞内是否存在ROS氧化细胞蛋白,谷胱甘肽均能诱导氧化还原反应发生转变,进一步使信号传导功能及转录因子分子功能发生改变。大量实验表明,ROS和GSH在多条细胞信号调节通路中发挥着重要作用。主要阐述了Fas、TNF-α和NF-κB信号通路及线粒体凋亡途径及GSH在这些通路中的作用。尤其是线粒体GSH耗竭能诱导线粒体内ROS显著增加,从而损害细胞生物能量和诱导线粒体通透性转换孔开启。根据线粒体损害程度,NF-κB信号通路可被抑制,肝细胞也可能经历不同的死亡模式(凋亡或坏死)并对刺激细胞死亡信号(如TNF-α)也更敏感。这些过程涉及许多肝脏疾病的发病机理。     

北京市大气细颗粒污染物与老年呼吸系统疾病急诊就医关系的病例交叉研究

目的:探讨北京市大气细颗粒污染物对呼吸系统疾病急诊的影响。方法:收集2013年3月-2014年3月解放军305医院以及西三环的总参军训部北京第八干休所门诊部的临床病例急诊数据、北京市环境监测中心的大气细颗粒污染物和气象条件数据资料,应用病例交叉设计研究方法进行数据分析。结果:在控制气温、相对湿度的影响后,单向回顾性1:1配对病例交叉分析结果显示,滞后0天细颗粒物污染对慢性支气管炎、哮喘、慢性阻塞性肺病急诊影响的OR值最大,细颗粒物日平均浓度每升高10μg/m3,对应的OR值分别为1.032、1.033、1.035。结论:该研究区域内大气细颗粒物污染物浓度升高可以导致呼吸系统疾病相关的慢性支气管炎、哮喘、慢性阻塞性肺病疾病的急诊增加。     

The very low birth weight infant microbiome and childhood health

This review describes current understandings about the nature of the very low birth weight infant (VLBW) gut microbiome. VLBW infants often experience disruptive pregnancies and births, and prenatal factors can influence the maturity of the gut and immune system, and disturb microbial balance and succession. Many VLBWs experience rapid vaginal or Caesarean births. After birth these infants often have delays in enteral feeding, and many receive little or no mother's own milk. Furthermore the stressors of neonatal life in the hospital environment, common use of antibiotics, invasive procedures and maternal separation can contribute to dysbiosis. These infants experience gastrointestinal dysfunction, sepsis, transfusions, necrotizing enterocolitis, oxygen toxicity, and other pathophysiological consditions that affect the normal microbiota. The skin is susceptible to dysbiosis, due to its fragility and contact with NICU organisms. Dysbiosis in early life may resolve but little is known about the timing of the development of the signature gut microbiome in VLBWs. Dysbiosis has been associated with a number of physical and behavioral problems, including autism spectrum disorders, allergy and asthma, gastrointestinal disease, obesity, depression, and anxiety. Dysbiosis may be prevented or ameliorated in part by prenatal care, breast milk feeding, skin to skin contact, use of antibiotics only when necessary, and vigilance during infancy and early childhood. Birth Defects Research (Part C) 105:252–264, 2015. © 2015 Wiley Periodicals, Inc.     

Multivessel revascularisation versus infarct-related artery only revascularisation during the index primary PCI in STEMI patients with multivessel disease: a meta-analysis

Background

There are controversial data regarding infarct-related artery only (IRA-PCI) revascularisation versus multivessel revascularisation (MV-PCI) in ST-elevation myocardial infarction (STEMI) patients with multivessel disease undergoing primary percutaneous coronary intervention (PCI). We performed a meta-analysis comparing outcome in same stage MV-PCI versus IRA-PCI in STEMI patients with multivessel disease.

Methods

Systematic searches of studies comparing MV-PCI with IRA-PCI in the MEDLINE and the Cochrane Database of systematic reviews were conducted. A meta-analysis was performed of all available studies. Primary outcome was all-cause mortality. Secondary endpoints were re-infarction, revascularisation, bleeding and major adverse cardiac events (MACE).

Results

A total of 15 studies were identified with a total number of 35,975 patients. Mortality rate was significantly higher in the MV-PCI group compared with the IRA-PCI group, odds ratio (OR): 1.64 (1.46–1.85). Both the incidence of re-infarction and re-PCI were significantly lower in the MV-PCI group compared with the IRA-PCI group: OR 0.54 (0.34–0.88) and OR 0.67 (0.48–0.93), respectively. Bleeding complications occurred more often in the MV-PCI group as compared with the IRA-PCI group: OR 1.24 (1.08–1.42). Rates of MACE were comparable between the two groups.

Conclusions

MV-PCI during the index of primary PCI in STEMI patients is associated with a higher mortality rate, a higher risk of bleeding complications, but lower risk of re-intervention and re-infarction and comparable rates of MACE.     

Preventive study in subjects at risk of fatal familial insomnia: Innovative approach to rare diseases

The text describes a preventive clinical trial with drug treatment in a very rare neurodegenerative disease (Fatal familial Insomnia, FFI) designed with the help of individuals at genetic risk of developing the disease, asymptomatic carriers, who have agreed to be exposed over a 10-year period to doxycycline, an antibiotic with anti-prion activity. At least 10 carriers of the FFI mutation over 42 y old will be treated with doxycycline (100 mg/die) and the incidence of the disease will be compared to that of an historical dataset. For ethical reasons a randomized, double-blind, placebo-controlled trial was not feasible, however the study design and the statistical analysis ensure the scientific value of the results. This approach might represent an important breakthrough in terms of potential therapy and knowledge of rare diseases that could give some hopes to these neglected patients.     

Dried Blood Spots - Preparing and Processing for Use in Immunoassays and in Molecular Techniques

The idea of collecting blood on a paper card and subsequently using the dried blood spots (DBS) for diagnostic purposes originated a century ago. Since then, DBS testing for decades has remained predominantly focused on the diagnosis of infectious diseases especially in resource-limited settings or the systematic screening of newborns for inherited metabolic disorders and only recently have a variety of new and innovative DBS applications begun to emerge. For many years, pre-analytical variables were only inappropriately considered in the field of DBS testing and even today, with the exception of newborn screening, the entire pre-analytical phase, which comprises the preparation and processing of DBS for their final analysis has not been standardized. Given this background, a comprehensive step-by-step protocol, which covers al the essential phases, is proposed, i.e., collection of blood; preparation of blood spots; drying of blood spots; storage and transportation of DBS; elution of DBS, and finally analyses of DBS eluates. The effectiveness of this protocol was first evaluated with 1,762 coupled serum/DBS pairs for detecting markers of hepatitis B virus, hepatitis C virus, and human immunodeficiency virus infections on an automated analytical platform. In a second step, the protocol was utilized during a pilot study, which was conducted on active drug users in the German cities of Berlin and Essen.