Prevalence of Hepatitis Delta Virus (HDV) Infection in Chronic Hepatitis B Patients with Unusual Clinical Pictures

Background

Probably 5% of the HBV carriers have HDV super infection. The risk of fulminant hepatitis, cirrhosis and hepatocellular carcinoma is higher in superinfection than the settings when HBV is alone.

Objectives

The aim of this study was to evaluate the prevalence of HDV in Iranian HBV isolates and to compare their clinical and virological pictures as well as their HDV genetic variations with other worldwide isolates.

Patients and Methods

81 carriers with positive results for HBsAg with upper limit ranges of ALT and low or undetectable levels of HBV viral load who did not respond to HBV therapy were selected. After RT amplification of HDV Delta antigen, direct sequencing and phylogenetic study were performed to explore the genotype(s) and nucleotide/amino acid variations.

Results

12 (14.8%) patients had positive results for both HDV RNA and anti-HDV. The mean ALT level was higher in HDV positive patients (75.9 U/ML) than HBV-mono-infected individuals; however, the mean HBV viral load was lower in coinfected patients than HBV-mono-infected patients. Phylogenetically, genotype I was the only detected genotype, and the most closely related isolates were of Turkish, Italian and Mongolian origin. Within the delta Ag, there were 326 nucleotide mutations, of which 111 and 215 were silent and missense, respectively. The total number of amino acid substitution was 148; most were located in known functional/epitopic domains. There was no correlation between the numbers of amino acid mutations, with clinical, virological status of the patients.

Conclusions

HDV should be suspected in HBV carriers with unusual clinical and virological pictures. Relatedness of Iranian HDV isolates to Italian and Turkish sequences proposed a common Caucasian origin for the distribution of HDV genotype I in this ethnic group.     

Prevalence of Hepatitis D Virus Infection Among Patients With Chronic Hepatitis B Attending Birjand Hepatitis Clinic (East of Iran) in 2012

Background

Hepatitis delta virus (HDV) is a defective RNA virus dependent on Hepatitis B virus (HBV) infection for its replication and expression. All patients with HBV infection should be tested for the presence of HDV infection. It is estimated that approximately 5% of hepatitis B surface antigen (HbsAg) carriers in the world are HDV infected patients. HBV-HDV co-infection may lead to more severe acute disease and higher risks of fulminant hepatitis, cirrhosis, and hepatocellular carcinoma than those having HBV infection alone. Also, HBV infected patients with HDV super-infection have a higher rate of progression to chronic disease and serious complications.

Objectives

Our aim was to determine the prevalence of HDV infection among chronic hepatitis B (CHB) patients attending Birjand Hepatitis Clinic, East of Iran.

Materials and Methods

A cross-sectional analytical study was conducted on 413 CHB patients in 2012. Serology test for anti-HDV was measured by ELISA in these patients. CHB patients had positive hepatitis B surface antigen for at least 6 months before the study entrance.

Results

The mean age of CHB patients was 38.5± 11.9 years and 55.9% of them (231 patients) were male. There were 13 cases (3.1%) with HDV infection. There was no association between positive anti-HDV serology and factors such as age, gender, carrier state, liver enzymes, and positive hepatitis B e antigen (HBeAg) serology.

Conclusions

Although HDV had a low prevalence in our area, it is important for healthcare providers and policy makers to plan preventive strategies for HDV spread as well as HBV prevention programs among high risk population.     

《黄帝内经》中的体质学说及临床价值

《黄帝内经》体质学说认为体质形成与先天及后天因素有关, 并提出多种复杂的体质分类方法及理论体系, 以体质论病、论治、论养生的临床辨证思维。现代中医以《中医体质分类与判定标准》的出台为标杆佐证了《黄帝内经》体质学的价值。     

腰椎黄韧带厚度与椎管斜径比值对黄韧带肥厚致椎管狭窄的临床诊断价值

目的探讨黄韧带厚度与椎管斜径的比值对黄韧带肥厚致椎管狭窄诊断的优越性。方法对71例腰腿痛患者行CT／MR检查,以MR双旁正中矢状面图像上硬膜囊后方是否出现黄韧带压迹为依据分为阳性组和阴性组,同时对50例无腰腿痛志愿者行腰椎CT／MR检查：再以CT／MR轴面分别选取L3～4、L4～5、L5～S1间盘下缘层面,测量其黄韧带厚度与椎管斜径比值（简称厚度斜径比值）,分析其与MRI阳性符合率及临床症状体征的关系。结果阴性组（35倒）共210条黄韧带,厚度为（3．01±0．72）mm,厚度斜径比值为0．19±0．04：阳性组（36例）共119条黄韧带,厚度为（3．94±0．84）mm,厚度斜径比值为0．28±0．O6;对照组黄韧带厚度为（3．16±0．85）mm,厚度斜径比值为0．19±0．04,阳性组黄韧带厚度与阴性组或对照组间差异有统计学意义（P〈0．O5）,阳性组厚度斜径比值与阴性组或对照组间差异有统计学意义（F〈0．05）;“厚度斜径比值〉0．24为标准,其敏感性、特异性、阳性预测值分别为74．8％、89．6％、73．6％：黄韧带厚度、厚度斜径比值与临床症状均呈正相关性（r值分别为0．72、0．86,P值均〈0．05）;黄韧带厚度、厚度斜径比值两种测量方法对临床症状符合率差异有统计学意义（p〈0．05）。结论CT／MR测量黄韧带厚度斜径比值较单纯测量黄韧带厚度对判断黄韧带肥厚致椎管狭窄更有诊断意义。     

长三角生产性服务业与制造业集聚水平的测度与比较

长三角生产性服务业和制造业的集聚趋势基本保持一致,且两者之间有相互促进作用,但也存在时间滞后现象。长三角区域内形成了上海以金融保险等生产性服务业为主、江苏以科技相关服务业为主并向周边地区辐射的集聚态势。提高长三角产业集聚水平应该进一步强化政府管理、协调相关产业关系和发挥生产性服务业行业协会的引领作用。     

Cardioprotective effect of δ-opioid receptor agonist vs mild therapeutic hypothermia in a rat model of cardiac arrest with extracorporeal life support

Background

To compare the effect of δ-opioid receptor agonist, d-Ala2-d-Leu5 enkephalin (DADLE) with normothermic control and therapeutic hypothermia on post resuscitation myocardial function in a model of extracorporeal life support (ECLS).

Methods

Ventricular fibrillation (VF) was induced in male Wistar rats. After 10 min of untreated VF, venoarterial ECLS was instituted for 60 min. At the beginning of ECLS animals were randomized to three groups of ten: normothermia, hypothermia (32 °C) and DADLE intravenous infusion (1 mg/kg/h). Cooling to 32 °C or normothermia or drug infusion lasted for the entire ECLS. Plasma samples and myocardial biopsies were obtained and left-ventricular (LV) function was assessed by a conductance catheter at baseline and after weaning from ECLS.

Results

DADLE administration resulted in a significantly enhanced recovery of LV systolic function expressed by slope of the LV end-systolic pressure volume relationship (Ees) and preload recruitable stroke work (PRSW) than hypothermia and normothermia. LV stiffness indicated by end-diastolic pressure volume relationship (EDPVR) was significantly lower after DADLE administration (P < 0.01). LV relaxation described by Tau was preserved after DADLE treatment but not after normothermia or mild hypothermia (P < 0.01). Plasma lactate concentrations were lower in DADLE group (P < 0.05). DADLE and not conventional hypothermia significantly increased phosphorylation of the kinases ERK1 and 2 (3.9 ± 0.3 and 3.1 ± 0.5 vs 0.4 ± 0.1 and 0.3 ± 0.1-fold of baseline levels) (P < 0.001). Both DADLE and hypothermia but not normothermia increase phosphorylation of Akt.

Conclusions

DADLE was more effective than mild therapeutic hypothermia in recovering myocardial function and activation of the pro-survival kinases Akt and ERK after ECLS.     

深圳市大沙河、观澜河藁杆双脐螺分布及其生态环境调查

目的了解深圳市大沙河、观澜河曼氏血吸虫中间宿主-藁杆双脐螺的分布及其生态环境。方法分别在目标河流的上游、中游和下游布点调查,手采法收集发现的淡水螺,实验室形态鉴定螺种,观察并描述其滋生环境。结果在观澜河的上游、中游、下游以及大沙河的上游、中游查见藁杆双脐螺活体;缓流、水草丰富、腐殖质较多且水质较好的水体环境,双脐螺生长良好,数量多,平均螺体较大。结论藁杆双脐螺在深圳大沙河、观澜河广泛存在,水体环境适宜双脐螺的生长繁殖。     

A Comparison of Confidence Interval Methods for the Concordance Correlation Coefficient and Intraclass Correlation Coefficient with Small Number of Raters

The intraclass correlation coefficient (ICC) with fixed raters or, equivalently, the concordance correlation coefficient (CCC) for continuous outcomes is a widely accepted aggregate index of agreement in settings with small number of raters. Quantifying the precision of the CCC by constructing its confidence interval (CI) is important in early drug development applications, in particular in qualification of biomarker platforms. In recent years, there have been several new methods proposed for construction of CIs for the CCC, but their comprehensive comparison has not been attempted. The methods consisted of the delta method and jackknifing with and without Fisher's Z-transformation, respectively, and Bayesian methods with vague priors. In this study, we carried out a simulation study, with data simulated from multivariate normal as well as heavier tailed distribution (t-distribution with 5 degrees of freedom), to compare the state-of-the-art methods for assigning CI to the CCC. When the data are normally distributed, the jackknifing with Fisher's Z-transformation (JZ) tended to provide superior coverage and the difference between it and the closest competitor, the Bayesian method with the Jeffreys prior was in general minimal. For the nonnormal data, the jackknife methods, especially the JZ method, provided the coverage probabilities closest to the nominal in contrast to the others which yielded overly liberal coverage. Approaches based upon the delta method and Bayesian method with conjugate prior generally provided slightly narrower intervals and larger lower bounds than others, though this was offset by their poor coverage. Finally, we illustrated the utility of the CIs for the CCC in an example of a wake after sleep onset (WASO) biomarker, which is frequently used in clinical sleep studies of drugs for treatment of insomnia.     

Multivariate Equivalence Tests for Use in Pharmaceutical Development

Statistical equivalence analyses are well-established parts of many studies in the biomedical sciences. Also in pharmaceutical development and manufacturing equivalence testing methods are required in order to statistically establish similarities between machines, process components, or complete processes. This article presents a choice of multivariate equivalence testing procedures for normally distributed data as generalizations of existing univariate methods. In all derived methods, variability is interpreted as nuisance parameter. The use of the proposed methods in pharmaceutical development is demonstrated with a comparative analysis of dissolution profiles.     

浅谈开阖枢理论在《金匮要略》疟病治疗中的运用

开阖枢理论源自《黄帝内经》中的三阴三阳气化思想,张仲景继承发展了开阖枢理论,并将其运用在《金匮要略》疟病的治疗中,使之能结合具体疾病展现出来,为疟病的治疗开拓了新的思路。通过对条文中方证的分析,总结张仲景在疟病中对太阳开、少阳枢和阳明阖,阳明阖和太阳开,太阳开和太阴开这3组开阖枢关系的精湛运用。