NASH患者外周血乏氧诱导因子1a-反义RNA 1和自噬基因Beclin1变化及其临床意义*

目的 研究非酒精性脂肪性肝炎(NASH)患者外周血单个核细胞(PBMC)乏氧诱导因子1a-反义RNA 1(HIF1a-AS1)和血清自噬基因beclin1水平变化及其临床意义。方法 2019年1月～2021年4月我院诊治的NASH患者118例(早期纤维化、进展期纤维化和肝硬化分别为43例、46例和29例)和同期健康体检者118例,使用全自动生化分析仪检测空腹血糖(FBG)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)水平,采用实时荧光定量PCR法检测PBMC HIF1a-AS1水平,采用ELISA法检测血清beclin1水平。结果 NASH患者FBG、血清TC、TG、LDL-C、PBMC HIF1a-AS1和血清beclin1水平分别为(5.9±1.6)mmol/L、(6.2±0.5)mmol/L、(2.4±0.6)mmol/L、(3.7±0.9)mmol/L、(1.9±0.2)和(5.7±1.9)ng/mL,显著高于健康者【分别为(4.8±0.7)mmol/L、(5.3±0.3)mmol/L、(1.3±0.3)mmol/L、(2.3±0.6)mmol/L、(1.0±0.1)和(4.1±1.5)ng/mL,P＜0.05】,而血清HDL-C水平为(1.2±0.2)mmol/L,显著低于健康者【(1.4±0.3)mmol/L,P＜0.05】;肝硬化患者FBG、血清TC、TG、LDL-C、PBMC HIF1a-AS1和血清beclin1水平分别为(6.8±2.0)mmol/L、(6.8±0.8)mmol/L、(2.8±0.7)mmol/L、(4.4±1.2)mmol/L、(2.5±0.3)和(6.4±2.1)ng/mL,显著高于早期纤维化患者【分别为(5.2±1.1)mmol/L、(5.7±0.4)mmol/L、(1.9±0.5)mmol/L、(3.1±1.0)mmol/L、(1.4±0.1)和(5.1±1.3)ng/mL,P＜0.05】;49例有高血压、糖尿病或/和高脂血症合并症的NASH患者FBG、血清TC、TG、LDL-C、PBMC HIF1a-AS1和血清beclin1水平分别为(6.5±1.9)mmol/L、(6.9±0.8)mmol/L、(2.7±0.8)mmol/L、(4.0±1.1)mmol/L、(2.2±0.3)和(6.3±2.0)ng/mL,显著高于69例无合并症者【分别为(5.5±1.3)mmol/L、(5.7±0.4)mmol/L、(2.2±0.5)mmol/L、(3.5±0.7)mmol/L、(1.7±0.2)和(5.3±1.6)ng/mL,P＜0.05】,而血清HDL-C水平为(1.1±0.2)mmol/L,显著低于无合并症者【(1.3±0.4)mmol/L,P＜0.05】。结论 NASH患者PBMC HIF1a-AS1和血清beclin1水平异常升高,监测其水平可能有助于病情评估。     

国外医学大数据研究进展及其启示

介绍大数据的概念、相关建设内容,分析国外医学大数据研究进展情况,包括美国、英国、澳大利亚等,从医疗卫生信息化基础建设、医学大数据平台建设和大数据组织体系与机制建设3个方面对我国医学大数据建设提出建议.     

鼻黏膜中一氧化氮合酶表达及其意义

目的了解正常鼻黏膜中一氧化氮合酶的分布特点及活性,并分析其在鼻黏膜中的生理作用。方法应用免疫组化法对20例正常鼻黏膜中内皮型一氧化氮合酶和诱导型一氧化氮合酶的表达情况进行检测,并应用分光光度法检测一氧化氮合酶活性,然后分析其表达特征,探讨其生理意义。结果正常鼻黏膜组织中有内皮型一氧化氮合酶表达,分布于黏膜上皮、腺体和血管内皮细胞;诱导型一氧化氮合酶偶见细胞表达;两者表达水平差异有显著性意义(P<0.01)。一氧化氮合酶活性1.526±0.310U/mgPro。结论鼻黏膜中主要表达内皮型一氧化氮合酶,分布于黏膜上皮、腺体和血管内皮细胞。由该酶产生的一氧化氮在鼻腔的正常生理功能中可能发挥重要作用。     

Executive Functions,Memory, and Social Cognitive Deficits and Recovery in Chronic Alcoholism: A Critical Review to Inform Future Research

Alcoholism is a complex and dynamic disease, punctuated by periods of abstinence and relapse, and influenced by a multitude of vulnerability factors. Chronic excessive alcohol consumption is associated with cognitive deficits, ranging from mild to severe, in executive functions, memory, and metacognitive abilities, with associated impairment in emotional processes and social cognition. These deficits can compromise efforts in initiating and sustaining abstinence by hampering efficacy of clinical treatment and can obstruct efforts in enabling good decision making success in interpersonal/social interactions, and awareness of cognitive and behavioral dysfunctions. Despite evidence for differences in recovery levels of selective cognitive processes, certain deficits can persist even with prolonged sobriety. Herein is presented a review of alcohol‐related cognitive impairments affecting component processes of executive functioning, memory, and the recently investigated cognitive domains of metamemory, social cognition, and emotional processing; also considered are trajectories of cognitive recovery with abstinence. Finally, in the spirit of critical review, limitations of current knowledge are noted and avenues for new research efforts are proposed that focus on (i) the interaction among emotion–cognition processes and identification of vulnerability factors contributing to the development of emotional and social processing deficits and (ii) the time line of cognitive recovery by tracking alcoholism's dynamic course of sobriety and relapse. Knowledge about the heterochronicity of cognitive recovery in alcoholism has the potential of indicating at which points during recovery intervention may be most beneficial.     

The genetics of alzheimer''s disease: A review and a discussion of the implications

This paper examines the evidence for a genetic etiology of Alzheimer's Disease. Three groups of cases are identified; the first being those with a consistently early age of onset, in which autosomal dominant inheritance can be established. These families may require genetic counseling, and represent an extraordinary resource for research. There are early onset cases without a strong genetic component, and later onset cases generally show only weak evidence of hereditary disease. Some of the apparent distinctions between these groups may result from methodologic problems, especially if the age of onset of symptoms is highly variable in the majority of families. Studies of associations between Alzheimer's Disease and Down's Syndrome suggest a role for genes on chromosome 21 in the genesis of the pathologic features, and testable hypotheses can be identified. Attempts to link the development of Alzheimer's Disease to the presence of specific inherited markers have generally been unsuccessful to date, but there are some promising findings. Recent progress in understanding the molecular basis of other inherited diseases is reviewed in relation to attempts to understand the possible molecular basis of Alzheimer's Disease. A limiting factor in future studies will probably be the availability of cells and tissues from pedigrees demonstrating autosomal dominant inheritance of this disorder.     

药物性肝损伤患者血清miR-21和miR-124a水平变化及其临床意义探讨

目的 探讨药物性肝损伤(DILI)患者血清微小RNA(miR)-21和miR-124a水平变化及其临床意义。方法 2019年3月～2022年3月我院收治的87例DILI患者和60例同期体检的健康人,采用实时荧光定量PCR法检测血清miR21和miR-124a mRNA水平,采用ELISA法检测核转录因子-κB(NF-κB)和白介素-6(IL-6)水平。结果 在DILI发生时,血清ALT、AST、GGT和TBIL峰值水平分别为(143.6±51.8)U/L、(158.2±38.8)U/L、(131.6±26.8)U/L和(41.9±9.6)μmol/L;DILI患者血清miR-21、miR124a mRNA、NF-κB和IL-6水平分别为(1.4±0.3)、(2.6±0.4)、(3615.4±526.4)pg/ml和(12.7±1.8)pg/ml,均显著高于健康人【分别为(1.0±0.1)、(1.1±0.1)、(692.2±144.6)pg/ml和(3.4±0.7)pg/ml,P<0.05】;混合型DILI患者血清NF-κB和IL-6水平分别为(3874.5±282.5)pg/ml...