水飞蓟宾-磷脂酰胆碱复合物对异硫氰酸-α-萘酯致小鼠肝损伤的保护作用

目的研究水飞蓟宾-磷脂酰胆碱复合物(SPC)对异硫氰酸-α-萘酯(ANIT)致小鼠急性肝损伤的保护作用。方法小鼠40只随机均分成4组:正常对照组、ANIT模型组、ANIT SPC低剂量(150 mg/kg)、ANIT SPC高剂量(300 mg/kg)组。前两组予0.5%羧甲基纤维素钠(CMC-Na)悬液灌胃,后两组分别予SPC(150、300 mg/kg)CMC-Na悬液灌胃,连续1周。末次予SPC 12 h后,正常对照组灌胃予花生油,余3组予ANIT 60 mg/kg(花生油配制),制成小鼠急性肝损伤模型,16 h(禁食不禁水12h)后摘眼球采血,分离血清,检测血清丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST)、血清总胆红素(TB)、丙二醛(MDA)、超氧化物歧化酶(SOD)水平。结果予ANIT后,模型组小鼠血清ALT、AST、TB、MDA明显升高,SOD活性明显降低;SPC能明显对抗这种改变,SPC组(1503、00 mg/kg)与模型组比较差异显著(P<0.05)。结论SPC对ANIT造成的急性肝损伤有明显的保护作用。     

磷脂酶A2激活在急性缺血性脑损伤中的作用机制及尼莫地平的保护作用

目的 探讨磷脂酶A2(PLA2)激活在急性缺血性脑损伤中的作用机制及尼莫地平的保护作用。方法 将局灶性脑缺血模型大鼠分为假手术组、缺血组及尼莫地平干预组，测定PIA活力、脑细胞游离ca^2 浓度、脑含水量及脑组织PLA2表达量的改变。结果 尼莫地平可使缺血后脑细胞游离ca^2 浓度、PIA2活性及脑组织含水量明显降低，但对脑缺血后脑组织PIA2mRNA表达降低不明显。结论 PIA2激活参与了急性脑损伤的病理过程，尼莫地平能抑制PLA2活性、降低细胞游离ca^2 浓度，减轻脑水肿的病理改变，对缺血性脑细胞损害有一定的保护作用。     

A cross-sectional study on the prevalence rate and influencing factors of nonalcoholic fatty liver disease in overweight/obese children北大核心CSCD

目的 调查医院就诊的超重/肥胖儿童非酒精性脂肪肝病(non-alcoholic fatty liver disease,NAFLD)的患病率,并探讨NAFLD发生的影响因素,为超重/肥胖儿童NAFLD的预防提供依据。方法 招募2019年6月-2021年9月在湖南省儿童医院就诊的超重/肥胖儿童作为研究对象,调查NAFLD患病率,并采用logistic回归分析探讨NAFLD,包括单纯性脂肪肝(non-alcoholic fatty liver,NAFL)和非酒精性脂肪肝炎(non-alcoholic steatohepatitis,NASH)发生的影响因素。采用受试者操作特征曲线分析评价影响因素对NAFL及NASH的预测价值。结果 共纳入844例超重/肥胖儿童,年龄为6~17岁。NAFLD患病率为38.2%(322/844),其中NAFL和NASH患病率分别为28.8%(243/844)和9.4%(79/844)。多因素logistic回归分析显示,腰臀比(waist-to-hip ratio,WHR)增加及低高密度脂蛋白胆固醇血症与NAFL和NASH的发生有关(P<0.05)。受试者操作特征曲线分析显示:WHR和高密度脂蛋白胆固醇联合检测预测NAFL的曲线下面积为0.653 (95%CI:0.613~0.694);二者联合检测预测NASH的曲线下面积为0.771 (95%CI:0.723~0.819)。结论 医院就诊的超重/肥胖儿童NAFLD的患病率较高;WHR和高密度脂蛋白胆固醇与NAFLD的发生有关,二者联合检测对NAFLD的发生具有一定的预测价值。     

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非酒精性脂肪肝病(non-alcoholic fatty liver disease,NAFLD)是一种肝组织学改变与酒精性肝病相似但无过量饮酒史的临床综合征,主要包括单纯性脂肪浸润、非酒精性脂肪肝炎(nonalcoholic steatohepatitis,NASH)和脂肪性肝硬化三种病理类型。其发病机制包括以胰岛素抵抗为主的一次打击和以氧化应激/脂质过氧化损伤为主的二次     

Treatment of non-alcoholic fatty liver disease with metformin versus lifestyle intervention in insulin-resistant adolescents

Abstract:  The presence of fatty liver per ultrasound and liver-associated enzymes were measured in a select cohort of youth with both obesity and insulin resistance, and the effect of metformin on these parameters evaluated. Fifty obese, multiethnic, insulin-resistant adolescents (mean age 15.1 yr, mean body mass index 39.8 kg/m²) were randomized to receive lifestyle recommendations plus either twice per day doses of 850 mg of metformin or placebo. Fasting and post-glucose challenge biochemistries and liver ultrasounds were compared at baseline and 6 months. The prevalence of fatty liver was 74%, elevated alanine aminotransferase (ALT) 14%, aspartate aminotransferase (AST) 14%, and gamma-glutamyl transferase (GGT) 17%. Fatty liver was mild in 23%, moderate in 31%, and severe in 46%. Fatty liver was more common in male and Hispanic subjects and elevated ALT more common in Hispanic subjects. Subjects with fatty liver appeared more insulin resistant (higher fasting insulin and triglycerides, lower high-density lipoprotein cholesterol) and had higher ALT and AST. At 6 months, mean ALT, GGT, and fasting insulin improved significantly in all subjects. Fatty liver prevalence (p < 0.04), severity (p < 0.04), and fasting insulin (p < 0.025) improved significantly with metformin compared to placebo. Non-alcoholic fatty liver disease (NAFLD) occurs with a high prevalence and severity in obese, insulin-resistant adolescents. While metformin plus lifestyle intervention appears promising, defining NAFLD therapies capable of preventing fibrosis and cirrhosis requires further study.     

儿童青少年腰围身高比与非酒精性脂肪肝病关系的回顾性分析

背景：肥胖是导致儿童青少年人群非酒精性脂肪肝病（NAFLD）发生的重要原因之一,腰围身高比（WHtR）是反映内脏脂肪和评价儿童青少年心血管代谢风险的简单而准确的体格测量指标,但WHtR 与NAFLD的关系研究十分有限。 目的：分析儿童青少年WHtR与NAFLD的关系。 设计：常规体检数据的回顾性分析。 方法：以所有参加上海市闵行区2014至2020年住校学生健康体检的学生为研究对象,将血清ALT水平高于一般人群性别和年龄别第97.5百分位数水平定义为疑似NAFLD（简称NAFLD）。基于全国数据提示心血管代谢风险聚集的WHtR作为切点值,以男孩和女孩WHtR分别≥0.481和≥0.456定义为WHtR升高;以非条件二分类Logistic回归模型,校正年龄、性别等协变量后,分析WHtR升高与NAFLD的关系。通过计算AUC、敏感度、特异度、阳性预测值和阴性预测值,评价WHtR升高对NAFLD的区分效果。 主要结局指标：WHtR与NAFLD的关联性。 结果：与WHtR正常组相比,NAFLD患病率在 WHtR升高人群中显著升高（16.2% vs 2.3%, P<0.001）,且随着年龄的增长呈现上升趋势。在WHtR升高人群中,男孩NAFLD患病率高于女孩（21.6% vs 11.0%,P<0.001）,而在WHtR正常人群中男孩和女孩的NAFLD患病率接近（2.3% vs 2.2%, P=0.71）。WHtR升高人群NAFLD的发生风险增加 71%,校正的OR =1.71,95% CI：1.26~2.31,P=0.001。分层分析结果显示WHtR升高分别能增加男孩77%（OR=1.77,95% CI：1.19~2.63,P=0.005）和女孩69% （OR=1.69,95% CI：1.05~2.71,P=0.005）的NAFLD发生风险 。WHtR升高区分NAFLD的AUC为0.73（95% CI：0.71~0.76）,敏感度63.2%、特异度83.4%、阳性预测值16.8%和阴性预测值97.7%。 结论：儿童青少年WHtR升高与NAFLD的发生独立相关;学校和社区等基层医疗保健机构要重点关注WHtR升高的人群,除了血压、糖脂代谢异常以外,还需特别关注NAFLD的患病情况。     

Association of uric acid levels with components of metabolic syndrome and non-alcoholic fatty liver disease in overweight or obese children and adolescents

ObjectiveTo investigate the association between serum uric acid concentration according to the presence or absence of non-alcoholic fatty liver disease (NAFLD) and/or metabolic syndrome (MS) in overweight or obese children and adolescents.MethodsThis was a cross-sectional study conducted from April of 2009 to March of 2010, including 129 children and adolescents treated at the Center for Childhood Obesity. Anthropometric data, blood pressure measurements, and laboratory test results were obtained, and NAFLD diagnosis was made by ultrasound. The diagnosis of MS was made using the criteria of the National Cholesterol Education Program/Adult Treatment Panel III, adapted to age range. The chi-squared test or or Fisher's test were used to evaluate the association of uric acid with the groups, with a 95% confidence interval. One-way analysis of variance (ANOVA) was used for comparison of means. Multiple logistic regression was used for adjustment of variables. The data were analyzed with the Statistical Package for Social Sciences (SPSS), release 17.ResultsHigh levels of uric acid were significantly associated with adolescence, MS, and systolic blood pressure. The highest quartile of uric acid showed significantly higher values of body mass index, waist circumference, systolic blood pressure, diastolic blood pressure, triglycerides, total cholesterol, and homeostatic model assessment index (HOMA-IR), and lower mean values of HDL cholesterol. In the final model, only age range and the presence of MS remained associated with uric acid levels.ConclusionsHigh levels of uric acid were associated with MS and adolescence, which was not observed with NAFLD.     

IL-17A,MCP-1, CCR-2, and ABCA1 polymorphisms in children with non-alcoholic fatty liver disease

ObjectiveThe prevalence of non-alcoholic fatty liver disease in children has risen significantly, owing to the worldwide childhood obesity epidemic in the last two decades. Non-alcoholic fatty liver disease is closely linked to sedentary lifestyle, increased body mass index, and visceral adiposity. In addition, individual genetic variations also have a role in the development and progression of non-alcoholic fatty liver disease. The aim of this study was to investigate the gene polymorphisms of MCP-1 (-2518 A/G) (rs1024611), CCR-2 (190 G/A) (rs1799864), ABCA1 (883 G/A) (rs4149313), and IL-17A (-197 G/A) (rs2275913) in obese Turkish children with non-alcoholic fatty liver disease.MethodsThe study recruited 186 obese children aged 10–17 years, including 101 children with non-alcoholic fatty liver disease and 85 children without non-alcoholic fatty liver disease. Anthropometric measurements, insulin resistance, a liver panel, a lipid profile, liver ultrasound examination, and genotyping of the four variants were performed.ResultsNo difference was found between the groups in respect to age and gender, body mass index, waist/hip ratio, or body fat ratio. In addition to the elevated ALT levels, AST and GGT levels were found significantly higher in the non-alcoholic fatty liver disease group compared to the non non-alcoholic fatty liver disease group (p < 0.05). The A-allele of IL-17A (-197 G/A) (rs2275913) was associated with non-alcoholic fatty liver disease (odds ratio [OR] 2.05, 95% confidence interval: 1.12–3.77, p = 0.02).ConclusionsThe findings of this study suggest that there may be an association between IL-17A (-197 G/A) (rs2275913) polymorphism and non-alcoholic fatty liver disease development in obese Turkish children.