Prediction model for hepatitis B e antigen seroconversion in chronic hepatitis B with peginterferon-alfa treated based on a responseguided therapy strategy

BACKGROUND Models for predicting hepatitis B e antigen(HBeAg)seroconversion in patients with HBeAg-positive chronic hepatitis B(CHB)after nucleos(t)ide analog treatment are rare.AIM To establish a simple scoring model based on a response-guided therapy(RGT)strategy for predicting HBeAg seroconversion and hepatitis B surface antigen(HBsAg)clearance.METHODS In this study,75 previously treated patients with HBeAg-positive CHB underwent a 52-week peginterferon-alfa(PEG-IFNα)treatment and a 24-wk follow-up.Logistic regression analysis was used to assess parameters at baseline,week 12,and week 24 to predict HBeAg seroconversion at 24 wk post-treatment.The two best predictors at each time point were used to establish a prediction model for PEG-IFNαtherapy efficacy.Parameters at each time point that met the corresponding optimal cutoff thresholds were scored as 1 or 0.RESULTS The two most meaningful predictors were HBsAg≤1000 IU/mL and HBeAg≤3 S/CO at baseline,HBsAg≤600 IU/mL and HBeAg≤3 S/CO at week 12,and HBsAg≤300 IU/mL and HBeAg≤2 S/CO at week 24.With a total score of 0 vs 2 at baseline,week 12,and week 24,the response rates were 23.8%,15.2%,and 11.1%vs 81.8%,80.0%,and 82.4%,respectively,and the HBsAg clearance rates were 2.4%,3.0%,and 0.0%,vs 54.5%,40.0%,and 41.2%,respectively.CONCLUSION We successfully established a predictive model and diagnosis-treatment process using the RGT strategy to predict HBeAg and HBsAg seroconversion in patients with HBeAg-positive CHB undergoing PEG-IFNαtherapy.

Efficacy of a Chinese herbal formula on hepatitis B e antigenpositive chronic hepatitis B patients

BACKGROUND No guideline recommends antiviral therapy for hepatitis B e antigen(HBeAg)-positive chronic hepatitis B patients with persistently normal alanine aminotransferase levels and a high hepatitis B virus(HBV)DNA viral load.AIM To evaluate the feasibility and safety of a Chinese herbal formula as a therapeutic option for chronic HBV infection.METHODS In total,395 patients(30–65 years old)with confirmed HBeAg-positive chronic hepatitis B infection and persistently normal alanine aminotransferase were randomized to receive either Chinese herbal formula or placebo for 96 wk.Endpoints to evaluate therapeutic efficacy included:(1)HBV DNA levels decreased to less than 4 log10 IU/mL at weeks 48 and 96;and(2)HBeAg clearance and seroconversion rates at weeks 48 and 96.RESULTS HBV DNA levels≤4 log10 IU/mL were 10.05%at week 48 and 18.59%at week 96 in the treatment group.The HBeAg clearance and conversion rates were 8.54%and 8.04%at week 48 and 16.08%and 14.57%at week 96,respectively.However,HBV DNA levels≤4 log10 IU/mL were 2.55%and 2.55%at weeks 48 and 96,respectively,and the HBeAg clearance rates were 3.06%and 5.61%at weeks 48 and 96,respectively,in the control group.The quantitative hepatitis B surface antigen and HBeAg levels at baseline and changes during the treatment period as well as the alanine aminotransferase elevation at weeks 12 and 24 were strong predictors of HBeAg clearance.CONCLUSION High rates of HBV DNA reduction,HBeAg clearance and seroconversion could be achieved with Chinese herbal formula treatments,and the treatments were relatively safe for HBeAg-positive chronic hepatitis B-infected patients with persistently normal alanine aminotransferase.The ability of the compound to modulate host immune function probably contributed to this effect.

Clinical significance of hepatitis B e antigen level measurement during long-term lamivudine therapy in chronic hepatitis B patients with e antigen positive

AIM： To determine the changes of quantitative hepatitis B e antigen （HBeAg） that predicts early detection of non-response or breakthrough to long-term lamivudine （LAM） therapy. METHODS： Among HBeAg positive chronic hepatitis B patients who failed to achieve HBeAg seroconversion within 12 too, we retrospectively analyzed 220 patients who had received LAM more than 24 too. RESULTS： The mean duration of LAM therapy was 36 （range, 24-72） mo. HBeAg seroconversion after the first 12 mo of LAM therapy was achieved in 53 （24.1%） patients. Viral breakthrough was observed in 105 （47.7%） patients. To find out whether the changing patterns of HBeAg levels can predict the outcome of LAM therapy, we analyzed the reduction rates of HBeAg levels during LAM therapy. Using the decrease more than 90% of pretreatment HBeAg levels, the sensitivity and specificity of response were 96.2% and 70.1%, respectively. Patients were divided into 3 groups according to the reduction patterns of the decrease of quantitative HBeAg： decrescendo, decrescendo-crescendo, no change or fluctuating groups. The optimal time to predict non-response or breakthrough was the first 9 mo of therapy. At 9 mo of therapy, 49 （92.5%） of 53 patients who had achieved HBeAg seroconversion were included in the decrescendo group. On the contrary, in the no change or fluctuating group, only four （7.5%） had achieved HBeAg seroconversion. Among patients who did not show the continuous decrease of HBeAg levels at 9 too, 95.2% （negative predictive value） failed to achieve HBeAg seroconversion. CONCLUSION： Almost all patients who failed to show a continuous decrease of HBeAg levels at 9 mo of LAM therapy were non-response or breakthrough. Therefore, monitoring changes of HBeAg levels during LAM therapy in HBeAg positive chronic hepatitis B may be valuable for identifying patients who are at high risk of non-response or breakthrough.

High-dose hepatitis B immunoglobulin therapy in hepatocellular carcinoma with hepatitis B virus-DNA/hepatitis B e antigen-positive patients after living donor liver transplantation

AIM: To investigate the impact of high-dose hepatitis B immunoglobulin(HBIG) on hepatocellular carcinoma(HCC) and hepatitis B virus(HBV) recurrence and overall survival after living donor liver transplantation(LDLT).METHODS: We investigated 168 patients who underwent LDLT due to HCC, and who were HBV-DNA/hepatitis B e antigen(HBe Ag)-positive, from January 2008 to December 2013. After assessing whether the patients met the Milan criteria, they were assigned to the low-dose HBIG group and high-dose HBIG group. Using the propensity score 1:1 matching method, 38 and 18 pairs were defined as adhering to and not adhering to the Milan criteria. For each pair, HCC recurrence, HBV recurrence and overall survival were analyzed by the Kaplan-Meier method and the log rank test according to the HBIG dose. RESULTS: Among those who met the Milan criteria, the 6-mo, 1-year, and 3-year HCC recurrence-free survival rates were 88.9%, 83.2%, and 83.2% in the low-dose HBIG group and 97.2%, 97.2%, and 97.2% in the high-dose HBIG group, respectively(P = 0.042).In contrast, among those who did not meet the Milan criteria, HCC recurrence did not differ according to the HBIG dose(P = 0.937). Moreover, HBV recurrence and overall survival did not differ according to the HBIG dose among those who met(P = 0.317 and 0.190, respectively) and did not meet(P = 0.350 and 0.987, respectively) the Milan criteria. CONCLUSION: High-dose HBIG therapy can reduce HCC recurrence in HBV-DNA/HBe Ag-positive patients after LDLT.

Practical approach in hepatitis b e antigen-negative individuals to identify treatment candidates

The natural history of chronic hepatitis B is characterized by different phases of infection,and patients may evolve from one phase to another or may revert to a previous phase.The hepatitis B e antigen(HBeAg)-negative form is the predominant infection worldwide,which consists of individuals with a range of viral replication and liver disease severity.Although alanine transaminase(ALT)remains the most accessible test available to clinicians for monitoring the liver disease status,further evaluations are required for some patients to assess if treatment is warranted.Guidance from practice guidelines together with thorough investigations and classifications of patients ensure recognition of who needs which level of care.This article aims to assist physicians in the assessment of HBeAgnegative individuals using liver biopsy or non-invasive tools such as hepatitis B s antigen quantification and transient elastography in addition to ALT and hepatitis B virus DNA,to identify who will remain stable,who will reactivate or at risk of disease progression hence will benefit from timely initiation of anti-viral therapy.

Hepatitis B surface antigen and hepatitis B core-related antigen kinetics after adding pegylated-interferon to nucleos(t)ids analogues in hepatitis B e antigen-negative patients

BACKGROUND Hepatitis B e antigen-negative chronic hepatitis B patients under nucleos(t)ids analogues(NAs)rarely achieve hepatitis B surface antigen(HBsAg)loss.AIM To evaluate if the addition of pegylated interferon(Peg-IFN)could decrease HBsAg and hepatitis B core-related antigen(HBcrAg)levels and increase HBsAg loss rate in patients under NAs therapy.METHODS Prospective,non-randomized,open-label trial evaluating the combination of Peg-IFN 180μg/week plus NAs during forty-eight weeks vs NAs in monotherapy.Hepatitis B e antigen-negative non-cirrhotic chronic hepatitis B patients of a tertiary hospital,under NAs therapy for at least 2 years and with undetectable viral load,were eligible.Patients with hepatitis C virus,hepatitis D virus or human immunodeficiency virus co-infection and liver transplanted patients were excluded.HBsAg and HBcrAg levels(log10 U/mL)were measured at baseline and during ninety-six weeks.HBsAg loss rate was evaluated in both groups.Adverse events were recorded in both groups.The kinetic of HBsAg for each treatment group was evaluated from baseline to weeks 24 and 48 by the slope of the HBsAg decline(log10 IU/mL/week)using a linear regression model.RESULTS Sixty-five patients were enrolled,61%receiving tenofovir and 33%entecavir.Thirty-six(55%)were included in Peg-IFN-NA group and 29(44%)in NA group.After matching by age and treatment duration,baseline HBsAg levels were comparable between groups(3.1 vs 3.2)(P=0.25).HBsAg levels at weeks 24,48 and 96 declined in Peg-IFN-NA group(-0.26,-0.40 and-0.44)and remained stable in NA group(-0.10,-0.10 and-0.10)(P<0.05).The slope of HBsAg decline in Peg-IFN-NA group(-0.02)was higher than in NA group(-0.00)(P=0.015).HBcrAg levels did not change.Eight(22%)patients discontinued Peg-IFN due to adverse events.The HBsAg loss was achieved in 3(8.3%)patients of the Peg-IFN-NA group and 0(0%)of the NA group.CONCLUSION The addition of Peg-IFN to NAs caused a greater and faster decrease of HBsAg levels compared to NA therapy.Side effects of Peg-IFN can limit its use in clinical practice.

Exploration of nucleos(t)ide analogs cessation in chronic hepatitis B patients with hepatitis B e antigen loss

BACKGROUND Nucleos(t)ide analogs(NAs)cessation in chronic hepatitis B(CHB)patients remains a matter of debate in clinical practice.Current guidelines recommend that patients with hepatitis B e antigen(HBeAg)seroconversion discontinue NAs after relatively long-term consolidation therapy.However,many patients fail to achieve HBeAg seroconversion after the long-term loss of HBeAg,even if hepatitis B surface antigen(HBsAg)loss occurs.It remains unclear whether NAs can be discontinued in this subset of patients.AIM To investigate the outcomes and factors associated with HBeAg-positive CHB patients with HBeAg loss(without hepatitis B e antibody)after cessation of NAs.METHODS We studied patients who discontinued NAs after achieving HBeAg loss.The Cox proportional hazards model was used to identify predictors for virological relapse after cessation of NAs.The cut-off value of the consolidation period was confirmed using receiver operating characteristic curves;we confirmed the cut-off value of HBsAg according to a previous study.The log-rank test was used to compare cumulative relapse rates among groups.We also studied patients with CHB who achieved HBeAg seroconversion and compared their cumulative relapse rates.Propensity score matching analysis(PSM)was used to balance baseline characteristics between the groups.RESULTS We included 83 patients with HBeAg loss.The mean age of these patients was 32.1±9.5 years,and the majority was male(67.5%).Thirty-eight patients relapsed,and the cumulative relapse rate at months 3,6,12,24,36,60,120,and 180 were 22.9%,36.1%,41.0%,43.5%,45.0%,45.0%,45.0%,and 52.8%,respectively.Twentysix(68.4%)patients relapsed in the first 3 mo after NAs cessation,and 35 patients(92.1%)relapsed in the first year after NAs cessation.Consolidation period(≥24 mo vs<24 mo)(HR 0.506,P=0.043)and HBsAg at cessation(≥100 IU/mL vs<100 IU/mL)(HR 14.869,P=0.008)were significant predictors in multivariate Cox regression.In the PSM cohort,which included 144 patients,there were lower cumulative relapse rates in patients with HBeAg seroconversion(P=0.036).CONCLUSION HBeAg-positive CHB patients with HBeAg loss may be able to discontinue NAs therapy after long-term consolidation,especially in patients with HBsAg at cessation<100 IU/mL.Careful monitoring,especially in the early stages after cessation,may ensure a favorable outcome.

On-treatment quantitative hepatitis B e antigen predicted response to nucleos(t)ide analogues in chronic hepatitis B

AIMTo investigate potential predictors for treatment response to nucleos(t)ide analogues (NAs) in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients. METHODSSeventy-six HBeAg-positive CHB patients received 96-wk NAs optimized therapy (lamivudine and adefovir dipivoxil) were studied retrospectively. Serum hepatitis B surface antigen, HBeAg, hepatitis B core antibody, hepatitis B virus (HBV) DNA and alanine aminotransferase levels were quantitatively measured before and during the treatment at 12 and 24 wk. Stepwise logistic regression analyses were performed to identify predictors for treatment response, and areas under the receiver operating characteristic curves (AUROC) of the independent predictors were calculated. RESULTSForty-three CHB patients (56.6%) achieved virological response (VR: HBV DNA &le; 300 copies/mL) and 15 patients (19.7%) developed HBeAg seroconversion (SC) after the 96-wk NAs treatment. The HBeAg level (OR = 0.45, P = 0.003) as well as its declined value (OR = 2.03, P = 0.024) at 24-wk independently predicted VR, with the AUROC of 0.788 and 0.736, respectively. The combination of HBeAg titer 1.6 lg PEIU/mL at 24-wk predicted VR with a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) of 85%, 100%, 100% and 83%, respectively, and the AUROC increased to 0.923. The HBeAg level (OR = 0.37, P = 0.013) as well as its declined value (OR = 2.02, P = 0.012) at 24-wk also independently predicted HBeAg SC, with the AUROC of 0.828 and 0.814, respectively. The HBeAg titer 2.2 lg PEIU/mL at 24-wk predicted HBeAg SC with a sensitivity, specificity, PPV, NPV of 88%, 98%, 88% and 98%, respectively, and the AUROC reached 0.928. CONCLUSIONThe combination of HBeAg level and its declined value at 24-wk may be used as a reference parameter to optimize NAs therapy.

Convergence Rate of E·B Estimation for Location Parameter Function of One-side Truncated Family Under NA Samples

In this paper, we construct the E·B estimation for parameter function of one-side truncated distribution under NA samples. Also, we obtain its convergence rate at O(n-q), where q is approaching 1/2.

Models for predicting hepatitis B e antigen seroconversion in response to interferon-α in chronic hepatitis B patients

AIM:To develop models to predict hepatitis B e antigen(HBe Ag)seroconversion in response to interferon(IFN)-αtreatment in chronic hepatitis B patients.METHODS:We enrolled 147 treatment-nave HBe Agpositive chronic hepatitis B patients in China and analyzed variables after initiating IFN-α1b treatment.Patients were tested for serum alanine aminotransferase(ALT),hepatitis B virus-DNA,hepatitis B surface antigen(HBs Ag),antibody to hepatitis B surface antigen,HBe Ag,antibody to hepatitis B e antigen(anti-HBe),and antibody to hepatitis B core antigen(anti-HBc)at baseline and 12 wk,24 wk,and 52 wk after initiating treatment.We performed univariate analysis to identify response predictors among the variables.Multivariate models to predict treatment response were constructed at baseline,12 wk,and 24 wk.RESULTS:At baseline,the 3 factors correlating most with HBe Ag seroconversion were serum ALT level>4×the upper limit of normal(ULN),HBe Ag≤500 S/CO,and anti-HBc>11.4 S/CO.At 12 wk,the 3 factors most associated with HBe Ag seroconversion were HBe Ag level≤250 S/CO,decline in HBe Ag>1 log10 S/CO,and anti-HBc>11.8 S/CO.At 24 wk,the 3 factors most associated with HBe Ag seroconversion were HBe Ag level≤5 S/CO,anti-HBc>11.4 S/CO,and decline in HBe Ag>2 log10 S/CO.Each variable was assigned a score of1,a score of 0 was given if patients did not have any of the 3 variables.The 3 factors most strongly correlating with HBe Ag seroconversion at each time point were used to build models to predict the outcome after IFN-αtreatment.When the score was 3,the response rates at the 3 time points were 57.7%,83.3%,and 84.0%,respectively.When the score was 0,the response rates were 2.9%,0.0%,and 2.1%,respectively.CONCLUSION:Models with good negative and positive predictive values were developed to calculate the probability of response to IFN-αtherapy.

献血者HEV感染合并HBV感染的特征分析

目的探讨合肥地区献血者中戊型肝炎病毒合并乙型肝炎病毒感染情况与特征分析,分析其与HBsAg/HBV DNA检测结果的关系。方法随机抽取2021年7月1日—2023年2月25日无偿献血者标本1301份纳入研究对象,根据HBsAg和HBV DNA检测结果将标本分为3组,HBsAg阳性组169份标本、HBsAg阴性组102份标本、合格组1030份标本分别采用酶联免疫吸附试验(ELISA)检测血浆中HEV Ag、抗HEV-IgM和抗HEV-IgG。依据抗HEV抗体检测结果采用RT-PCR法对合格组标本100份、HBsAg阳性组标本20份、HBsAg阴性组标本30份进行HEV RNA检测。分析3组献血者中抗HEV-IgM和抗HEVIgG检测阳性献血者基本情况进行统计分析。结果3组1301份标本HEV Ag检测均为阴性。HBsAg阴性组检出抗HEV阳性率为22.55%,与HBsAg阳性组相比(22.55%vs 17.75%)差异无统计学意义(P>0.05);但与合格组相比(22.55%vs 13.79%),差异有统计学意义(P<0.05)。HBsAg阳性组和合格组均检出抗HEV-IgG+IgM抗体,阳性率分别为1.18%和0.29%,且合格组检出抗HEV-IgM抗体阳性率为0.39%。留取3组150份标本未检出HEV RNA。HBsAg阴性组随着献血者年龄的增长检出抗HEV抗体阳性率有升高趋势,但差异无统计学意义(P>0.05)。HBsAg阳性组和合格组抗-HEV抗体阳性率在41~50岁人群最高,分别为27.27%和27.04%,其次是51~55岁人群。1301份标本检出抗HEV抗体阳性男性献血者151人,阳性率16.74%,女性45人,阳性率11.28%,检出抗HEV阳性男女人数之比为3.5∶1,差异有统计学意义(P<0.05)。结论合肥地区献血者中存在HEV感染合并HBV感染,多为既往感染,也存在急性感染,HBV隐匿感染状态中HEV感染者居多。

HBeAg诱导的免疫激活和免疫抑制在慢性乙型肝炎中的作用

HBV感染诱导的慢性乙型肝炎是导致肝硬化和肝癌的重要危险因素。半个世纪前,HBeAg在HBV感染者血清中首次被发现,尽管HBeAg并不参与HBV在肝细胞中的感染或复制,但其已被证实可干扰宿主先天性和适应性免疫反应,在慢性HBV感染的过程中发挥着重要的免疫激活和免疫抑制作用。HBV对于感染的肝细胞并没有细胞毒性,免疫应答介导的抗病毒作用和炎症反应决定HBV是否被清除或者诱导肝脏炎症相关疾病。因此,本文对HBeAg的形成及其在慢性HBV感染中引起的免疫激活和免疫抑制机制进行综述,重点论述HBeAg对先天免疫和适应性免疫细胞所引起的不同免疫效应,阐述了其诱导免疫反应的两面性,并探讨HBeAg在慢性HBV感染不同阶段间的转换作用。

HBV相关慢加急性肝衰竭患者血清SDC-1、ZEB1表达水平与近期预后的相关性分析

目的分析血清多配体蛋白聚糖-1(SDC-1)、E盒结合锌指蛋白1(ZEB1)水平与乙型肝炎病毒相关慢加急性肝衰竭(HBV-ACLF)近期预后的关系。方法选取濮阳市人民医院2020年1月至2022年10月收治的130例HBV-ACLF患者和130例慢性乙型肝炎(CHB)患者,纳入同期130例健康体检者为对照组。比较3组血清SDC-1、ZEB1水平。对HBV-ACLF患者进行3个月随访,分为生存组(76例)和死亡组(54例),比较不同预后患者一般资料及血清SDC-1、ZEB1水平;分析血清SDC-1、ZEB1、终末期肝病模型(MELD)评分对HBV-ACLF患者预后的评估价值;分析HBV-ACLF预后的影响因素。结果CHB组、HBV-ACLF组患者血清SDC-1、ZEB1水平高于对照组(P<0.05),HBV-ACLF组高于CHB组(P<0.05)。死亡组HBV-ACLF患者白蛋白低于生存组(P<0.05),血清SDC-1、ZEB1水平及MELD评分高于生存组(P<0.05)。血清SDC-1、ZEB1、MELD评分联合预测HBV-ACLF患者预后的曲线下面积(AUC)大于单独预测。MELD评分、SDC-1、ZEB1是HBV-ACLF患者死亡的危险因素(P<0.05)。结论HBV-ACLF患者血清SDC-1、ZEB1水平均与近期预后相关,且血清SDC-1、ZEB1与MELD评分联合预测HBV-ACLF患者近期预后的价值最高。

IKBKE在乙型肝炎病毒相关肝癌组织中的表达及临床意义

目的探究IKBKE在乙型肝炎病毒相关肝癌(HBV-HCC)组织中的表达及其与临床特征和预后的相关性。方法通过组织芯片免疫组织化学染色方法来检测HBV-HCC患者的癌组织和癌旁组织中B细胞编码κ轻链多肽基因抑制激酶E(IKBKE)的蛋白表达;整理并分析患者的一般资料、临床体征及病理报告结果,检测相关的血液指标;使用Pearson相关性分析比较IKBKE在肝细胞肝癌组织中的表达及其与患者的一般临床资料、临床体征、血液指标、病理结果和预后的相关性。结果该研究发现,在HBV相关的肝癌患者中,IKBKE的蛋白表达在癌组织中的表达水平显著高于正常组织,高表达组的生存时间明显低于低表达组。此外,IKBKE表达与肝硬化程度呈负相关,与TFF3、pCEA和Ki67等指标呈正相关。结论IKBKE、TFF3、pCEA和Ki67的联合检测有助于预测HBV相关肝癌的预后。

The research progress of an E//B neutral particle analyzer

An E//B neutral particle analyzer(NPA)has been designed and is under development at Sichuan University and Southwestern Institute of Physics.The main purpose of the E//B NPA is to measure the distribution function of fast ions in the HL-2A/3 tokamak.The E//B NPA contains three main units,i.e.the stripping unit,the analyzing unit and the detection unit.A gas stripping chamber was adopted as the stripping unit.The results of the simulations and beam tests for the stripping chamber are presented.Parallel electric and magnetic fields provided by a NdFeB permanent magnet and two parallel electric plates were designed and constructed for the analyzing unit.The calibration of the magnetic and electric fields was performed using a 50 kV electron cyclotron resonance ion source(ECRIS)platform.The detection unit consists of 32lutetium-yttrium oxyorthosilicate(LYSO)detector modules arranged in two rows.The response functions ofα,hydrogen ions(H^(+),H_(2)^(+)and H_(3)^(+))andγfor a detector module were measured with^(241)Am,^(137)Cs and^(152)Eu sources together with the 50 kV ECRIS platform.The overall results indicate that the designed E//B NPA device is capable of measuring the intensity of neutral hydrogen and deuteron atoms with energy higher than 20 keV.

句容抽蓄上水库筑坝料E-B模型分期反演参数对比分析

为预测句容抽蓄上水库坝体和库盆在竣工期和蓄水后产生的变形,利用施工期上库主坝和库盆的变形监测资料,对填筑料E-B模型参数进行分期反演。在此基础上,采用第三期反演参数,对竣工期和蓄水后的库盆变形特性进行预测和分析。研究表明,利用早期短时序坝体变形监测资料得到的模型反演参数偏大,随着坝体填筑高度的增加,采用后期长时序变形监测资料反演得到的模型参数逐渐减小并趋于真实值;在E-B模型中引入初始应力状态参数S0可以考虑现场压实坝料的超固结特性,S0越大,坝体变形越小,经历高强度碾压后的填筑料S0在0.40~0.55之间;基于第三期反演参数的库盆竣工期沉降计算结果与实测结果总体吻合较好。研究结果可用于指导工程实践。

葫芦素B、E的抗肿瘤作用和机制研究进展

癌症是世界各国首要的死亡原因,也是影响预期寿命的重要障碍,癌症防治形势严峻,因此亟需探索出好的治疗途径和有效的药物。葫芦素B、E是从葫芦科植物甜瓜、黄瓜、西瓜、丝瓜等植物中提取出来的一类高度氧化的葫芦烷型四环三萜类物质。在抗癌研究中显示出对多种癌细胞具有增殖抑制和抗转移的活性,其机制可能与破坏细胞骨架、干扰F-肌动蛋白、诱导细胞周期阻滞、诱导凋亡自噬、促进DNA损伤、诱导活性氧(ROS)形成以及诱导铁死亡有关,本文就葫芦素B、E的抗肿瘤作用和机制做一综述。Cancer is the leading cause of death and a major obstacle to life expectancy in all countries of the world, and the situation of cancer prevention and treatment is grim, so there is an urgent need to explore good therapeutic avenues and effective drugs. Cucurbitacin B and E are a class of highly oxidized cucurbitane-type tetracyclic triterpenoids extracted from cucurbit plants such as melon, cucumber, watermelon, loofah, and so on. In anticancer studies, they have shown proliferation inhibition and antimetastatic activity against a variety of cancer cells, and their mechanisms may be related to the destruction of the cytoskeleton, interference with F-actin, induction of cell cycle arrest, induction of apoptosis and autophagy, promotion of DNA damage, induction of reactive oxygen species (ROS) formation, and induction of ferroptosis. This article provides a review of the antitumor effects and mechanisms of cucurbitacin B and E.

Transformation of hepatitis B serologic markers in babies born to hepatitis B surface antigen positive mothers

AIM:To better understand the clinical significance of hepatitis B seroiogic markers in babies born to hepatitis B surface antigen (HBsAg) positive mothers, the incidence of maternal seroiogic markers of hepatitis B via placenta and its transformation in these babies were investigated. METHODS: Mothers with positive HBsAg were selected in the third trimester of pregnancy. Their babies received immunoprophylaxis with hepatitis B immunoglobulin and hepatitis B vaccine after birth, and were consecutively followed up for hepatitis B seroiogic markers and HBV DNA at birth, mo 1, 4, 7, 12, and 24. RESULTS: Forty-two babies entered the study, including 16 born to hepatitis B e antigen (HBeAg)-positive HBsAg carrier mothers and 26 to HBeAg-negative HBsAg carrier mothers. Apart from four babies born to HBeAg-positive carrier mothers and demonstrated persistent positive HBeAg eventually became HBV carriers, all other babies developed anti-HBs before 12 mo of age. Among the other 12 babies born to HBeAg-positive carrier mothers, HBeAg was detected in 7 at birth, in 4 at mo 1, and in none of them thereafter. No antibody response to the transplacental HBeAg was detected. Among the babies born to HBeAg-negative carrier mothers, anti-HBe was detected 100% at birth and mo 1, in 88.5% at mo 4, in 46.2% at mo 7, in 4.2% at mo 12 and none in mo 24. Among all the immunoprophylaxis-protected babies born to either HBeAg-positive or HBeAg-negative carrier mothers, anti-HBc was detected in 100% at birth, mo 1 and mo 4, in 78.9% at mo 7, in 36.1% at mo 12 and in none at mo 24. CONCLUSION: HBeAg can pass through human placenta from mother to fetus and become undetectable before 4 mo of age, but no antibodies response to the transplacental HBeAg can be detected till mo 24 in the immunoprophylaxis-protected babies. The sole existence of anti-HBe before 1 year of age or anti-HBc before 2 years of age in babies born to HBsAg carrier mothers may simply represent the transplacental maternal antibodies, instead of indicators of HBV infection status.

Cloning and expression and purification of Hepatitis B e-antigen precursor in Escherichia coli

OBJECTIVE: To investigate the role of the 25 kD hepatitis B e antigen (HBeAg) precursor that only exist inside hepatocytes and study its effect on the pathopoiesis of hepatitis B and QIAGEN expression and purification system. METHODS: Hepatitis B virus (HBV) preC/C gene for the 25 kD HBeAg precursor was cloned into the expression vector pQE30 and the 25 kD HBeAg precursor was expressed in Escherichia coli (E. coli) and purified. Its antigenicity for 21 kD mature HBeAg was tested by western blot analysis. RESULTS: Cloned fragments in the expression vector were sequenced and verified to be homogeneous with that of HBV (ayw subtype). Expression of the HBeAg precursor in E. coli under the transcriptional regulation of T5 promoter yielded a soluble cytosolic protein with an apparent molecular mass of 25 kD. Recombinant HBeAg precursor exhibited identical potencies with 21 kD mature HBeAg that reacted with anti-HBeAg antibodies. The purification rate of the expressed HBeAg precursor was up to 89.6% and the yield of purified HBeAg precursor from this procedure was 2.4 mg/L. CONCLUSION: 25 kD HBeAg precursor exhibited biological activity and might play an important role in pathopoiesis of hepatitis B.

Association of core promoter mutations of hepatitis B virus and viral load is different in HBeAg(+) and HBeAg(-) patients

AIM:To identify the prevalence of hepatitis B e antigen (HBeAg) and to assess the association of hepatitis B virus (HBV) core promoter mutations and viral load in Indonesian patients.METHODS:Sixty-four patients with chronic hepatitis,65 with liver cirrhosis and 50 with hepatocellular carcinoma were included in this study.HBeAg and hepatitis B e antibody (HBeAb) tests were performed using enzyme-linked immunosorbent assay and the mutations were analyzed by sequencing.Viral load was measured by real-time polymerase chain reaction.RESULTS:Of 179 patients,108 (60.3%) were HBeAg(-) and 86 (79.6%) of these HBeAg(-) patients had been seroconverted.The A1896 mutation was not found in HBeAg(+) patients,however,this mutation was detected in 70.7% of HBeAg(-) patients.This mutation was frequently found when HBeAg was not expressed (87.7%),compared to that found in HBeAg seroconverted patients (65.1%).The A1899 mutation was also more prevalent in HBeAg(-) than in HBeAg(+) patients (P=0.004).The T1762/A1764 mutation was frequently found in both HBeAg(+) and HBeAg(-) patients,however,the prevalence of this mutation did not significantly differ among the two groups (P=0.054).In HBeAg(+) patients,the T1762/A1764 mutation was correlated with lower HBV DNA (P < 0.001).The A1899 mutation did not correlate with HBV DNA (P=0.609).In HBeAg(-) patients,the T1762/A1764 mutation alone was not correlated with HBV DNA (P=0.095),however,the presence of either the T1762/A1764 or A1896 mutations was associated with increased HBV DNA (P < 0.001).CONCLUSION:The percentage of HBeAg(-) patients is high in Indonesia,and most of the HBeAg(-) patients had been seroconverted.The A1896 mutation was most likely the major cause of HBeAg loss.The T1762/A1764 mutation alone was associated with lower viral loads in HBeAg(+) patients,but not in HBeAg(-) patients.