慢性乙型肝炎患者丙氨酸氨基转移酶正常值上限下调必要性初步探讨

目的初步探讨慢性乙型肝炎(hepatitis B virus, HBV)患者目前采用的丙氨酸氨基转移酶正常值上限(upper limit of normal, ULN)下调的必要性.方法收集非活动性乙肝表面抗原(hepatitisBsurface antigen,HBsAg)携带者及接受抗病毒治疗慢性HBV患者715例,病毒DNA均低于检测值下限,其中非活动性HBsAg携带者组57例(携带组),慢性HBV抗病毒治疗组455例(肝炎组), ALT低于2 ULN经肝穿活检后抗病毒治疗组203例(其中ALT<1 ULN 133例, ALT1-2ULN70例)(肝穿组).收集患者年龄、性别、体重、肝功能、血糖、血脂、血常规、乙肝病毒感染血清学标志物、乙肝病毒DNA定量、甲胎蛋白、肝胆脾B超等相关数据.肝穿组收集肝组织炎症分级、纤维化分期及抗病毒治疗1年后肝功能数据.结果全部患者(n=715)ALT水平中位数为19 IU/L, 95%百分位数为31.2 IU/L(95%CI:30-34 IU/L), 95%百分位数男性为34 IU/L(95%CI:31-35 IU/L),女性为26.2 IU/L(95%CI:25-30IU/L).肝穿组患者抗病毒治疗后ALT值下降显著,中位数由37 IU/L降至23 IU/L,具显著统计学差异(F=111.497, P=0.000).根据4种不同ALT正常值上限,肝脏显著炎症(≥G2)的检出率分别为0,38.78%,63.27%和84.69%.以ROC分析ALT对肝组织学显著炎症的评估价值, AUC值(Az)为0.751,对ALT与肝组织学炎症程度作Logistic回归分析, P值为0.331.结论目前应用的ALT正常值上限对评估慢性HBV是偏高的,似乎存在下调的必要性.

Lactic acidosis during telbivudine treatment for HBV: A case report and literature review

All oral nucleoside analogues against hepatitis B virus,with an exception of telbivudine,have been reported causing lactic acidosis(LA).Here we report the first case of chronic hepatitis B developing severe refractory LA during telbivudine monotherapy.A 36-year-old man of Chinese origin received telbivudine antiviral treatment for chronic hepatitis B.After 11 mo of therapy,he developed anorexia,nausea,and vomiting with mild muscle weakness.The patient was found with elevated serum creatine phosphokinase up to 3683 U/L(upper limit of normal 170 U/L)and marked LA.LA did not resolve immediately following discontinuation of telbivudine.His condition began to improve after hemodialysis treatment for 16 times and usage of glucocorticosteroid.The patient fully recovered after 16 wk of treatment.This is the first documented case with severe LA caused by telbivudine monotherapy.Besides serum creatine phosphokinase,blood lactate level should also be closely monitored in patients receiving telbivudine.

Precore/basal core promoter mutants quantification throughout phases of hepatitis B virus infection by Simpleprobe

AIM:To investigate precore/basal core promoter(PC/BCP) mutants throughout hepatitis B virus(HBV) infection and to determine their relationship to hepatitis B early antigen(HBeA g) titers.METHODS:We enrolled 191 patients in various stages of HBV infection at the Huashan Hospital and the Taizhou Municipal Hospital from 2010 to 2012.None of the patients received antiviral therapy.HBV DNA from serum,was quantified by real-time PCR.The HBV genotype was determined by direct sequencing of the S gene.We used the Simpleprobe ultrasensitivequantitative method to detect PC/BCP mutants in each patient.We compared the strain number,percentage,and the changes in PC/BCP mutants in different phases,and analyzed the relationship between PC/BCP mutants and HBe Ag by multiple linear regression and logistic regression.RESULTS:Patients with HBV infection(n = 191) were assigned to groups by phase:Immune tolerance(IT) = 55,Immune clearance(IC) = 67,Low-replicative(LR) = 49,and HBeA g-negative hepatitis(ENH) = 20.Of the patients(male,112; female,79) enrolled,122 were HBe Ag-positive and 69 were HBe Ag-negative.The median age was 33 years(range:18-78 years).PC and BCP mutation detection rates were 84.82%(162/191) and 96.86%(185/191),respectively.In five HBe Ag-negative cases,we detected double mutation G1896A/G1899 A.The logarithm value of PC mutant quantities(log10 PC) significantly differed in IT,IC,and LR phases,as well as in the ENH phase(F = 49.350,P < 0.001).The logarithm value of BCP mutant quantities(log10 BCP) also differed during the four phases(F = 25.530,P < 0.001).Log10 PC and log10 BCP values were high in the IT and IC phases,decreased in the LR phase,and increased in the ENH phase,although the absolute value at this point remained lower than that in the IT and IC phases.PC mutant quantity per total viral load(PC%) and BCP mutant quantity per total viral load(BCP%) differed between phases(F = 20.040,P < 0.001; F = 10.830,P < 0.001),with PC% and BCP% gradually increasing in successive phases.HBeA g titers negatively correlated with PC%(Spearman's rho =-0.354,P < 0.001) and BCP%(Spearman's rho =-0.395,P < 0.001).The negative correlation between PC% and HBeA g status was significant(B =-5.281,P = 0.001),but there was no such correlation between BCP% and HBeA g status(B =-0.523,P = 0.552).CONCLUSION:PC/BCP mutants become predominant in a dynamic and continuous process.Log10 PC,log10 BCP,PC% and BCP% might be combined to evaluate disease progression.PC% determines HBeA g status.

Exonuclease Ⅰ and Ⅲ improve the detection efficacy of hepatitis B virus covalently closed circular DNA

Background: Hepatitis B virus covalently closed circular DNA (HBV cccDNA) is an important biomarker of hepatitis B virus infection. However, the current methods are not specific and sensitive. The present study aimed to develop a specific and sensitive assay method for the quantification of HBV cccDNA. Methods: Exonuclease Ⅰ(Exo Ⅰ)& Exonuclease Ⅲ(Exo Ⅲ) and specific primer probes are used in real-time PCR. The virus particles isolated from peripheral blood mononuclear cells were used as negative control and HBV1.3 recombinant plasmid 3.2 kb circular DNA fragment was used as positive control. The methods of cccDNA detection were evaluated in cell lines, plasmid, animal model, patient serum and liver biopsies. Results: A linear range of 10 1 –10 7 copies/assay using specific primers for HBV cccDNA was established. HBV cccDNA were only detected in cell lines, animal model and liver tissue. It cannot be detected in serum samples. Intrahepatic HBV cccDNA level had good correlation with intrahepatic total HBV DNA level ( r = 0.765, P < 0.001). Conclusions: The real-time quantitative PCR is an effective and feasible method for sensitive and specific detection of low copy number of cccDNA. The novel detection method is fast, provides high sensitivity and specificity and can be used in clinical practice.

A new alvarezsaurid dinosaur from the Late cretaceous Qiupa Formation of Luanchuan,Henan Province,central China

An alvarezsaurid dinosaur skeleton was discovered from the Late Cretaceous Qiupa Formation of Luanchuan,Henan Province of eenttral China.It represents a new alvarezsaurid dinosaur Qiupanykus zhangi gen.et sp.nov.A phylogenetic analysis recovers Qiupanykus nested within the unresolved clade,which includes Asian and north American taxa.The skeleton of the new specimen is preserved in association with eggshells.The eggshell morphologies show that these eggs belong to oviraptorid eggs,skeletal remains of which were discovered from the same area.The alvarezsaurid skeleton associated with eggshell fragments may indicate that these eggs were broken by the strong thumb-claws of the former and that alvarezsaurid dinosaurs may be egg-eaters.

Gigacycle Fatigue Behavior of 1800 MPa Grade High Strength Spring Steel for Automobile Lightweight

Gigacycle fatigue behavior of 60Si2CrVA high strength spring steel was investigated by ultrasonic fatigue test machine. Fatigue fractography was observed by scanning electron microscopy （SEM）. Maximum inclusion sizes and fatigue strength in different volumes were estimated by statistics of extreme values （SEV） and generalized Pareto distribution （GPD） methods. The results showed that S N curves of 60Si2CrVA spring steels for two rolling processes were not horizontal asymptotes but a gradient in a regime of 109 cycles, and traditional fatigue limits were eliminated. Surface machined topography and inclusions in steel were major factors that led to elimination of fatigue limit for 60Si2CrVA spring steel. The SEV and GPD methods could effectively predict size of the maximum inclusion and fatigue strength in different volumes of 60Si2CrVA spring steel. Predicted fatigue strength was in accordance with experimental results by ultrasonic fatigue testing.

The role of prophylactic antibiotics in hepatitis B virus-related acute-on-chronic liver failure patients at risk of bacterial infection: a retrospective study

Background:Acute-on-chronic liver failure(ACLF)is characterized by an excessive systemic inflammatory response and organ failure and has high mortality.Bacterial infections(Bis)worsen the clinical course of ACLF and carry a poor prognosis in ACLF patients.The efficacy of third-generation cephalosporins has been challenged in recent years.The aim of this study was to characterize the difference between ACLF patients with and without Bis and to provide a reference for medical intervention.

Microstructure and properties of continuous casting Ag-28Cu-8Sn alloy fabricated by dieless drawing

Ag-28Cu-8Sn(wt%)alloy is a widely used brittle silver-based brazing filler metal.The wire of brazing filler metal was prepared by continuous casting process and dieless drawing technology.The phase structure was measured by X-ray diffraction(XRD),and the microstructure of wetting interface,cast states,processing states and fracture morphologies were characterized by the optical microscopy(OM)and scanning electron microscopy(SEM),respectively.The electrical conductivity,hardness,tensile strength and elongation rate were tested as well.Furthermore,the solid-liquid phase temperature was measured by a differential scanning calorimeter(DSC),and the wettability of brazing filler metal was tested by spreading method.The outcomes obtained show that the as-cast microstructure is a typical three-zone structure,including region of surface fine grain,zone of columnar grain and region of center equiaxed crystal.Ag-28Cu-8Sn alloy is mainly composed of Ag-rich a-phase,Cu-rich pphase and intermediate compounds.Grain refinement appears in the cross section,as for grains of the longitudinal section,the shape is changed from ribbon to fiber to form a silk texture.The strength and hardness improve with the increase in the true strain,while the conductivity and elongation are reduced.Furthermore,the solid-phase temperature is 605.9℃,and the liquid-phase temperature is 725.1℃.The spreading area of Ag-28Cu-8Sn brazing filler metal is 174 mm^2,and the metallurgical bonding occurs between Ag-28Cu-8Sn brazing filler metal and Cu matrix.In addition,compared with cold drawing process,there are not any microcracks at the fracture morphology for the alloy fabricated by dieless drawing.The dieless drawing process overcomes some processing defects of traditional cold drawing,and the processing performance of Ag-28Cu-8Sn alloy is improved.