Background & Aims: Hyperuricemia is a common feature of patients with non-alcoholic fatty liver disease (NAFLD). This study aimed to explore the causal relationship and underlying mechanisms between NAFLD and hyperuricemia.Methods: We evaluated the impact of NAFLD on the development of hyperuricemia in a cohort of 5541 baseline hyperuricemia-free individuals. We further analyzed xanthine oxidase (XO), a rate-limiting enzyme that catalyzes uric acid production, as a candidate to link NAFLD and hyperuricemia.Results: In the first study, a 7-year prospective analysis found that NAFLD was strongly associated with subsequent development of hyperuricemia. Cox proportional hazards regression analyses showed that age, gender, and body mass index adjusted hazard ratio (95% confidence interval) for incident hyperuricemia was 1.609 (1.129-2.294) in individuals with NAFLD, as compared with those without NAFLD at baseline. In the second study, we observed that expression and activity of XO were significantly increased in cellular and mouse models of NAFLD. Knocking down XO expression or inhibiting XO activity significantly decreases uric acid production and attenuates free fatty acids-induced fat accumulation in HepG2 cells. Inhibiting XO activity also significantly prevents the development of and ameliorates established hepatic steatosis induced by a high-fat diet in mice. Further experiments indicated that XO regulates activation of the NLRP3 inflammasome, which may be essential for the regulatory effect of XO on NAFLD.Conclusions: NAFLD significantly increases the risk of incident hyperuricemia. XO is a mediator of the relationship between NAFLD and hyperuricemia, and may serve as a novel therapeutic target for the two linked diseases. (C) 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Objective To investigate the role and possible mechanism of caveolin-1 (CAV1) in the forming of cholesterol gallstone in mice fed with lithogenic diet.Methods Cholesterol gallstone susceptible C57BL/6 mice were study objects.The mice of control group (n=6) and experiment group (n=6) were fed with normal diet and lithogenic diet for four weeks respectively.The condition of cholesterol gallstone forming,changes of serum lipid and bile composition were measured,and the expressions of CAV1 and scavenger receptor classB member Ⅰ (SR-BⅠ) at mRNA and protein level in the liver and gallbladder were detected by realtime-polymerase chain reaction and Western blot,respectively.The t test was performed for mean comparsion between the two groups.Results The incidence rate of gallstone in experimental group was 100％ after fed with lithogenic diet for four weeks,the lipid level significantly increased,and the proportion of cholesterol in bile raised and bile salt decreased.Compared with those of control group,the expressions of CAV1 at mRNA and protein level in the liver and gallbladder tissues siginificantly decreased (in liver tissue,mRNA 0.53 ± 0.13 vs 1.00 ± 0.32,t =3.330,protein level 0.39 ± 0.07vs 0.92±0.06,t=10.280; in gallbladder tissue,mRNA 0.40±0.22 vs 1.00±0.22,t=3.823,protein level 1.04±0.07 vs 1.34 ± 0.04,t =6.367,all P＜0.01).There was no significant difference in the relative expression of SR-BⅠ at mRNA and protein level in the liver and gallbladder tissues between the mice of experiment group and control group.Conclusion The changes of CAV 1 expression at mRNA and protein level in liver and gallbladder tissues may affect lipids metabolism and cholesterol transportation in liver and gallbladder tissues of experiment mice,which might play an important role in the formation of cholesterol gallstone.

胆囊胆固醇结石症是全球常见公共健康问题之一,我国发病率为7％～10％,其确切的发病机制目前尚不清楚,也缺乏疗效确切的治疗药物和预防措施[1].近期研究发现清道夫受体B族Ⅰ型(scavenger receptor class B typeⅠ,SR-BI)介导的肝细胞对高密度脂蛋白(high density lipoprotein,HDL)中胆固醇酯的摄取与胆囊胆固醇结石的形成有关,微囊蛋白-1/3(eaveolin-1/3)与SR-B工均位于肝胆细胞膜的微囊,具有抑制SR-BⅠ活性、提高血浆HDL水平和增加胆道胆盐分泌的作用,可能与该病的发生有关[2-3].本研究拟通过检测高脂致石餐干预后C57BL/6小鼠肝脏和胆囊组织中的微囊蛋白-1/3、SR-B Ⅰ、胆囊收缩素受体(cholecystokinin receptor,CCK-R)的表达,以及血脂和胆道脂质含量变化,探讨这些因素在实验动物胆囊胆固醇结石形成中的可能作用。

BACKGROUND: Alcohol, overweight, and lipid metabolism contribute to fatty liver and atherosclerosis pathogenesis.OBJECTIVE: To study the association of alcoholic intake, overweight, and dyslipidemia.METHODS: We randomly selected 482 age- and sex-matched individuals from East China. Gender, age, education level, smoking, hypertension, daily alcohol intake, drinking duration, and body mass index (BMI) were evaluated in association with triglyceride, total cholesterol, high-density (HDL-C), and low-density lipoprotein-cholesterol.RESULTS: The association between dyslipidemia and 8 predictors of disease was made by regression analysis through the generalized additive model. The results showed that age, daily alcohol intake, and BMI were all closely associated with hypertriglyceridemia. Age, duration of drinking, and BMI were all closely associated with hypercholesterolemia. Age and BMI status were both closely associated with high LDL-C levels. By contrast, none of the 8 predictors was closely associated with low HDL-C levels (all P < .05).CONCLUSIONS: Daily alcohol intake was a risk factor for hypertriglyceridemia. By contrast, drinking duration was a protective factor against hypercholesterolemia. Age and BMI were important risk factors for dyslipidemia (excluding HDL-C). (C) 2014 National Lipid Association. All rights reserved.

AIM To investigate the association between serum alpha-fetoprotein (AFP) levels and fatty liver disease (FLD) in a Chinese population. METHODS A cross-sectional study was performed among subjects who presented for a health examination at the First Affiliated Hospital, College of Medicine, Zhejiang University in 2013. FLD was diagnosed based on an ultrasonography examination. Serum AFP levels were measured with a chemiluminescence immunoassay. RESULTS Of the 9800 subjects enrolled, 2601 were diagnosed with FLD. Subjects with FLD had higher serum AFP levels than those without the disease. Subjects with high serum AFP levels had a higher prevalence of FLD, metabolic syndrome, and its components. Univariate logistic analysis showed that elevated serum AFP levels were associated with an increased risk of FLD (OR = 1.057, 95%CI: 1.031-1.084). However, after adjusting for covariates, AFP no longer remained significantly associated with the risk factors for FLD. CONCLUSION Our results suggest that serum AFP levels are significantly associated with FLD and that AFP acts as a cofactor, but not as an independent factor, for FLD.

AIM:To investigate the role of caveolin-3 (CAV3) and cholecystokinin A receptor (CCKAR) in cholesterol gallstone disease (CGD).METHODS:To establish a mouse model of CGD, male C57BL/6 mice were fed with a lithogenic diet containing 1.0% cholic acid, 1.25% cholesterol and 15% fat; a similar control group was given a normal diet. The fresh liver weights and liver-to-body weight ratio were compared between the two groups after one month. Serum lipid profile and bile composition were determined with an autoanalyzer. The Cav3 and Cckar mRNA and CAV3 and CCKAR protein levels in the liver and gallbladder were determined via real-time polymerase chain reaction and Western blot, respectively.RESULTS:Establishment of the mouse CGD model was verified by the presence of cholesterol gallstones in mice fed the lithogenic diet. Compared with mice maintained on a normal diet, those fed the lithogenic diet had significantly higher mean liver-to-body weight ratio (0.067 ± 0.007 vs 0.039 ± 0.007, P < 0.01), serum total cholesterol (4.22 ± 0.46 mmol/L vs 2.21 ± 0.11 mmol/L, P < 0.001), bile total cholesterol (1.33 ± 0.33 mmol/L vs 0.21 ± 0.11 mmol/L, P < 0.001), and bile phospholipid concentrations (3.55 ± 1.40 mmol/L vs 1.55 ± 0.63 mmol/L, P = 0.04), but lower total bile acid concentrations (726.48 ± 51.83 μmol/L vs 839.83 ± 23.74 μmol/L, P = 0.007). The lithogenic diet was also associated with significantly lower CAV3 in the liver and lower CAV3 and CCKAR in the gallbladder compared with the control mice (all P < 0.05).CONCLUSION:CAV3 and CCKAR may be involved in cholesterol gallstone disease.

Event-related potential (ERP) is a reliable neuroelectric measure of brain activity that helps to confirm the assessment of mental status and cognitive impairment. Many studies have reported that alcoholics show a significantly lower ERP P300 amplitude than the norm. In the present study, ERP P300 waves were measured to evaluate the effect of citric acid on cognitive function during excessive alcohol consumption in healthy adults. Five volunteers were selected through clinical interview, physical examination, and psychiatric assessment for participation in this study. In a double-blind placebo-controlled before-after design, each subject was treated with 5 ml/kg body weight alcohol, 5 ml/kg body weight alcohol and 1 mg citric acid, or a placebo on three separate occasions, one week apart. ERP P300, blood biochemical indicators, blood alcohol concentrations (BACs) and acetaldehyde concentrations were assessed. Repeated measure analysis of variance (ANOVA) with a within-subjects factor was used to evaluate differences in blood biochemical indicators, BACs, blood acetaldehyde concentrations, and ERP P300 in the three sessions of assessments. Several blood biochemical indicators showed significant differences between treatments, including the levels of cholinesterase (CHE), total bile acid (TBA), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), and glycylproline dipeptidyl aminopeptidase (GPDA). BACs after consumption of alcohol alone or citric acid with alcohol were significantly higher compared to those after placebo treatment (P < 0.05). There were no significant differences in blood acetaldehyde concentrations between the treatments. The P300 amplitudes on the frontal (Fz), central (Cz), and parietal (Pz) regions of the scalp after consumption of alcohol were significantly lower than those after consumption of the placebo or citric acid with alcohol (P < 0.05), while there were no significant differences between the latter two treatments. The results of this study suggest that citric acid could reduce the decline in ERP P300 amplitude and cognitive ability induced by acute alcohol consumption. It may also affect some blood biochemical indicators, but the specific mechanisms need further research.

室温、冰箱温度是实验室的主要环境参数,对保证试剂、标本的质量具有重要意义.开发基于DS18820温度传感器和B/S软件体系结构的温度监测系统,实现24小时不间断的温度监测、控制、记录和处理,实现不同地点众多冰箱温度和室温的统一管理,可提高实验室温度监控的工作效率和自动化程度.

目的评价Bactec MGIT 960系统自临床标本分离分枝杆菌的价值。方法收集临床标本共578份,分别接种于BactecMGIT 960系统和改良罗氏培养基,分离到的分枝杆菌用荧光PCR进行菌种鉴定。结果 578份临床标本中,共分离出171株分枝杆菌(29.6%)。两种方法均阳性有105株,仅Bactec MGIT 960系统阳性有54株,仅罗氏培养基阳性有12株。BactecMGIT 960系统分离率为27.5%(159/578),罗氏培养基法为20.2%(117/578)。Bactec MGIT 960系统法阳性平均报告时间为10.2 d,罗氏培养基法为27.5 d。Bactec MGIT 960系统法污染率为7.6%,罗氏培养基法为4.3%。结论 Bactec MGIT 960分枝杆菌检测技术是一种较好的快速分离分枝杆菌的方法,联合改良罗氏培养基可进一步提高分离率。

ABSTRACT A multiplex real-time PCR assay was developed to simultaneously detect and discriminate influenza A virus subtypes, including novel H1N1 (2009) and seasonal H3N2 virus, influenza B virus, and respiratory syncytial virus (RSV) in a single test tube, with detection sensitivity and specificity of 99% and 100%, respectively, for the four pathogens.

目的 通过测定事件相关电位(ERP)p300来评估大量饮酒对健康成人认知能力的影响及饮酒时服用α-酮戊二酸改善认知能力的作用.方法 选择5位健康在职职工进行临床问诊、体格检查及精神评估,每位受试者均接受3次试验,分别在连续的3周内进行.第1周的周一进行第1次实验,给予5ml/kg体重的饮用水;第2周的周一进行第2次实验,给予5ml/kg体重的38%乙醇;第3周的周一进行第3次实验,给予 5ml/kg体重的38%乙醇加1mg α-酮戊二酸.每次实验中均在给予干预后60min抽血进行血生化指标、血乙醇及乙醛浓度测定,然后进行ERP p300测定.结果 3组间血生化指标的差异无统计学意义(P ＞0.05);血乙醇及血乙醛浓度在饮酒或饮酒并服用α-酮戊二酸时较不饮酒时显著升高(P＜0.05),并有统计学意义,而饮酒和饮酒并服用α-酮戊二酸两种情况之间比较,血乙醇及乙醛浓度差异无统计学意义(P ＞0.05);饮酒后p300在Fz、Cz、Pz三点的波幅降低,与不饮酒相比有统计学差异;饮酒并服用α-酮戊二酸较只饮酒相比p300在Fz、Cz、Pz 3点的波幅升高差异有统计学意义(P＜0.05);3次实验间p300在各点的潜伏期无统计学差异.结论 大量饮酒后人的认知能力降低,饮酒时服用α-酮戊二酸可改善因饮酒引起的人认知能力的降低.

Objective To conduct a cohort study of the effect of alcohol and obesity on liver enzymes in China.Methods To study 500 individuals of liver enzymes normality randomly in the 1999-year epidemiological survey, and liver enzyme levels (461 complete data) in 2006.Results Logistic-regression analysis showed a daily alcohol intake of at least 40 g, duration of drinking at least 10 years, and obesity, which were closely related to abnormality in liver enzyme levels; the relative risk (95% confidence interval) was 2.014 (1.108-3.662), 2.085 (1.106-3.928), and 1.772 (1.140-2.754), respectively (all P < 0.05). According to the value of daily alcohol intake/duration of drinking and body mass index (BMI) to categorize, seven-year cumulative incidence of liver enzymes levels abnormality for the daily alcohol intake at least 40 g and obesity group or the duration of drinking at least 10 years and obesity group was the highest, 51.47 and 47.12%, respectively. No significant dose-response relationship was found between daily alcohol intake/duration of drinking and liver enzyme level abnormalities.Conclusion The risk of alcohol consumption and obesity-inducing liver injury together is far greater than the risk of a single factor inducing liver injury. An alcoholic threshold effect may be more important than a dose-response effect on liver enzyme levels. Eur J Gastroenterol Hepatol 22:820-825 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

<正>成人血红蛋白(Hb)通常由HbA(97%)、HbA2(2.5%)和HbF(0.5%)组成。对HbA进行色谱分析发现了几种次要血红蛋白,即HbA1a、HbA1b、HbA1c(统称为HbA1)和快速血红蛋白(HbA0),HbA1和HbA0统称为糖化血红蛋白[1]。HbA1的主要成分为HbA1c,约占80%,它是评估糖尿病人血糖控制情况的重要指标。

目的 研究抗凝血标本全血放置以及离心后保存温度和时间对血浆凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)检测结果 的影响.方法 取 PT和APTT正常值标本180例(PT在10.5～14.0 s之间,APTT在22.0～36.0 s之间),异常值(高值)标本120例(PT＞14.0s,APTT＞36.0s),用SysmexCA7000型全自动血凝分析仅及其配套试剂,分别检测抗凝血标本全血室温(26℃)放置及离心后在室温及冰箱(4℃)保存条件下0,2,4,6,8,12,24 h时PT,APlvr的结果 ,并将所得到的数据用统计学方法 进行处理.结果 全血室温放置时,正常值标本PT在4 h内,APTT在2 h内的测定结果 与0 h测定结果 比较差异无统计学意义(P＞0.05);异常值标本PT,APTT在2 h内的测定结果 与0 h测定结果 比较差异无统计学意义(P＞0.05).离心后血浆在室温下,正常值标本PT在6 h内,APTT在4 h内的测定结果 与0 h测定结果 比较差异无统计学意义(P＞0.05);异常值标本PT,APTT在4 h内的测定结果 与0 h测定结果 比较差异无统计学意义(P＞0.05).离心后血浆在冰葙保存条件下,正常值及异常值标本PT,APTT在6 h内的测定结果 与0 h测定结果 比较差异无统计学意义(P＞0.05).结论 凝血标本采集后,如果不能即刻测定,最好离心后置于冰箱保存,并保证在6h内完成测定;如果不离心室温放置,应在2 h内完成测定.

肿瘤标志物的研究与应用在肿瘤学中已成为一个引人注目的新领域.研究表明,血清肿瘤标志物的最佳联合检测对于胰腺癌诊断、疗效观察、监测复发或转移、指导治疗及判断预后有重要的意义.国内外大量文献显示联合检测是目前较为理想的肿瘤标志物;肿瘤标志物有望在胰腺癌l临床中成为早期诊断、预后判断及调整治疗的工具,CA19-9、CA24-2、K-ras、p53和p16肿瘤标志物具有重要的应用价值.现结合国内外近年来的文献,就肿瘤标志物在胰腺癌诊治中的研究进展作一综述.

Objective To To explore the antioxidation of paraoxonase-1 (PON1), superoxide dismutase (SOD) and malondiadehyde (MDA) as markers of oxidative stress in patients with acute organophosphorus pesticide poisoning (AOPP). Methods The levels of PON-1, SOD and MDA were measured in 28 cases and compared with 36 controls.Results The levels of PON-1 and SOD in cases were significantly lower than in controls (P0.01), while the level of MDA was significantly higher in cases. The activity of PON-1 was negatively correlated with the content of MDA in the patients with acute organophosphorus pesticide poisoning by correlation analysis (r=-0.821, P0.01).Conclusions The oxidative damage caused by the decrease of antioxidative enzymes activity plays a pathophysiological role in the acute organphosphorus pesticide poisoning.

Aggregation of leukocytes in vitro is a rare phenomenon and may result in pseudoleukopenia, Here we report on 2 cases of different types of leukocyte aggregation, both of which were detected by unstable white blood cell (WBC) counts. Case 1 related to a 21-year-old male who was diagnosed as having pneumonia and was found to have a cold-temperature-dependent neutrophil aggregation. Case 2 related to a 36-year-old female who had no obvious clinical disease and was found to have a slow aggregation of neutrophils, lymphocytes, monocytes, and eosinophils. With the leukocyte aggregation, it was found that the VCS parameters (mean channels of cell volume, conductivity, and light scatter) generated by the Coulter LH 750 hematology analyzer changed obviously, especially the increase of neutrophil volume distribution width (NDW). This suggests that the VCS parameters, especially NDW, might be used as an adjunct indicator of leukocyte aggregation along with the unstable WBC counts or unexplained low WBC counts.

Objective To investigate the association of serum lipid,lipoprotein,apolipoprotein,leptin,cholecystokinin(CCK)and bile lipid with cholesterol gallstone formation.Methods The patients with gallstone were divided into cholesterol(n=99)and non-cholesterol(n=57)gallstone groups by infrared spectometry.And 52 healthy volunteers were served as control group.The concentrations of serum cholesterol,triglyceride,high and low density lipoproteins,apolipoprotein(Apo),leptin and CCK were measured and compared among three groups.The levels of total bile cholesterol,bile acid and lecithin were also detected.Results The concentrations of serum triglyeeride and total cholesterol in two gallstone groups were higher than those in control group(P value all＜0.01).The level of Apo-B in cholesterol gallstone group was higher than that in control group(P=0.017).While the concentrations of high density lipoprotein and CCK were significantly lower in two gallstone groups than those in control group(P value all=0.000).Serum leptin was higher in male patients compared to controls(P＜0.05).The bile cholesterol saturation index in two gallstone groups was above 1.Conclusions The changes of serum CCK,triglyceride,total cholesterol,high density lipoprotein,Apo-B and leptin may be correlated to the formation of gallbladder gallstone.

酗酒相关各种疾病已构成较严重的公共卫生问题.西方国家饮酒人群中酒精性肝病(ALD)的患病率高达84%,且嗜酒者中约有20%～30%可发展为酒精性肝硬化[1].近10余年来,酒精相关性疾病在我国日益受到重视.酒精性肝病在此类疾病中较为突出,受到临床关注.同时,酒精性肝损伤可增加肌体对HBV和HCV的易感性.HBV感染在我国人群中较常见,但尚无有关ALD伴HBV感染率的确切数据.我们对浙江省酒精性肝病合并乙肝病毒感染人群进行调查,现将结果报告如下.

Objective Analyze the historical data of critical values lists,providing scientific evidence for continuous improvement of critical value systems.Methods Screen out critical value lists data of 2006 from laboratory information system,after pretreatment and transformation of data,calculate the percentage of critical value,and its daily distribution,weekly distribution and department distribution, evaluate the range and turnaround time for critical value.Results The rate of critical value was 1.67%.It was mainly concentrated from 8 to 13 O'clock.Monday and Thursday have more critical value than other days.From the perspective of department,the majority critical value was from hematology department and transplantation department.After the evaluation of distribution diagram of critical value range,the lower critical value limit of blood potassium was adjusted from 3.0 mmol/L to 2.8 mmol/L,the blood platelet and leukocyte counts for parlents with hematology disease were a(Ijusted from 20×109/L,1.5×109/L to 10×1O9/L,1.0×109/L respectively.The laboratory turnaround time for 76.2% critical value was less than 1 hour.Conclusion Review and analyze critical value lists data regularly can improve the work efficiency and quality for the laboratory and clinic department and better meet patients' safety needs.