Bioinformatics Analyses of Potential miRNA-mRNA Regulatory Axis in HBV-related Hepatocellular Carcinoma

Aims: We aimed to explore the crucial miRNA-mRNA axis through bioinformatics analysis and provide evidences for the development of pathophysiological mechanisms and new therapies for HBV-related HCC.Methods: MiRNA ({"type":"entrez-geo","attrs":{"text":"GSE76903","term_id":"76903"}}GSE76903) and mRNA ({"type":"entrez-geo","attrs":{"text":"GSE77509","term_id":"77509"}}GSE77509) dataset were used to screen differentially expressed miRNAs (DE-miRNAs) and differentially expressed mRNAs (DE-mRNAs) using R software. Overlapping genes between DE-mRNAs and target genes of DE-miRNAs were identified as candidate genes. Hub genes were obtained via cytohubba analysis. The expression at protein and mRNA levels and prognostic value of hub genes were evaluated based on The Cancer Genome Atlas (TCGA) data. Key miRNA-mRNA axes were constructed according to predicted miRNA-mRNA pairs. MiRNA expression and prognostic role were respectively identified using starBase v3.0 and Kaplan-Meier plotter database. Real-time PCR was performed to verify the expression of crucial miRNAs and mRNAs. Coexpression of crucial miRNA and mRNA were analyzed using starBase v3.0.Results: CDK1, CCNB1, CKS2 and CCNE1 were screened as hub genes, which were significantly upregulated at protein and mRNA levels. These up-regulated hub genes were also significantly associated with poor prognosis. Hsa-mir-195-5p/CDK1, hsa-mir-5589-3p/CCNB1 and hsa-let-7c-3p/CKS2 were screened as critical miRNA-mRNA axes. Critical miRNAs were decreased in HCC, which indicates unfavourable prognosis. QPCR results showed that crucial miRNAs were decreased, whereas critical mRNAs were increased in HBV-related HCC. A reverse relationship between miRNA and mRNA in crucial axis was further verified.Conclusion: This study identified several miRNA-mRNA axes in HBV-related HCC. Hsa-mir-195-5p/CDK1, hsa-mir-5589-3p/CCNB1 and hsa-let-7c-3p/CKS2 might serve as potential prognostic biomarkers and therapeutic targets for HBV-related HCC.     

HBV感染免疫耐受期孕妇分娩前后 临床指标及细胞因子水平变化特征

[摘要]　目的　分析HBV感染免疫耐受期孕妇分娩前后临床指标及细胞因子水平的变化规律，比较分娩后不同ALT水平组孕妇血清细胞因子水平差异。方法　选择2015年1月—2017年12月就诊于首都医科大学附属北京佑安医院的HBV感染免疫耐受期孕妇52例，妊娠28周给予替比夫定（telbivudine, LdT）抗病毒干预，分别于LdT干预前（基线）、分娩前（2周）及分娩后（6周）进行生化、血清学及病毒学检测，同步留取相应时间点外周血标本进行细胞因子检测，并分析分娩前后临床指标及细胞因子水平的变化特征。结果　52例患者分娩后6周ALT水平均值明显高于LdT干预前和分娩前，其中ALT≥2倍正常值上限（upper limit of normal, ULN）者达28.8%（15/52例）；与LdT干预前相比，分娩前HBV DNA水平显著下降，平均降幅达（3.68±0.79） lg IU/ml；HBsAg和HBeAg水平在分娩前后无明显变化。与分娩后ALT＜2倍ULN组相比，ALT≥2倍ULN组的IFN-γ水平在LdT干预前呈低水平表达，分娩后呈高水平表达，差异均有统计学意义（Z=2.284，P=0.022；Z=2.223，P=0.026）；2组间IL-2、IL-4、IL-6、IL-10、TNF-α在LdT干预前、分娩前及分娩后均无明显差异。结论　HBV感染免疫耐受期孕妇分娩后部分患者ALT明显升高，结合分娩前后细胞因子的动态变化，提示分娩后可能出现免疫功能增强并打破机体对HBV的免疫耐受，这或许有利于分娩后的抗病毒治疗，但仍须要进一步深入的研究。     

IgE anti Hepatitis B virus surface antigen antibodies detected in serum from inner city asthmatic and non asthmatic children

Viral Hepatitis type B (HBV) is a public health concern, but has not been linked to asthma. Immunoglobulin (Ig) G is involved in HBV immune responses; less is known about IgE antibodies (Abs) against HBV in asthma. Given the importance of HBV, we sought to determine whether HBV vaccine contributes to asthma in children, by stimulating specific IgE production. Total IgE, IgE- or IgG-anti-HBVs Abs were studied in vaccinated pediatric asthmatics and non asthmatics. We found: (1) total IgE was higher in asthmatics; (2) total IgE did not correlate with IgE anti-HBVs; (3) IgE anti-HBVs did correlate with IgG-anti-HBVs in all subjects; (4)IgE- and IgG-HBVs Abs were similar in both groups; (5) IgE- or IgG anti-HBVs Abs did not correlate with age. Our findings indicate that HBV vaccination induces IgE responses in asthmatics and non asthmatics.     

宁夏地区朝觐人员HBV感染者基因分型研究

目的了解宁夏地区朝觐人员乙型肝炎基因分布特点,为探讨宁夏地区朝觐人员乙肝流行趋势提供科学依据。方法采用ELISA法对宁夏地区2010至2012后采用荧光PCR检测方法,对乙肝病毒感染者进行基因分型。结果 90例乙型肝炎HBs Ag阳性者HBV DNA经荧光PCR方法分型,B型5例(5.56%),C型82例(91.11%),其他型3例(3.33%),经统计学分析不同基因型分布有统计学意义;HBV DNA基因型在性别中分布无差异,因此,认为性别与乙肝基因型不具有相关性。结论宁夏地区朝觐人员乙型肝炎患者HBV基因型分布基本符合我国北方的分布特点,以C型为主。     

Hepatitis B virus e antigen (HBeAg) may have a negative effect on dendritic cell generation

Hepatitis B virus (HBV) continues to be a serious worldwide health problem despite the use of protective HBV vaccines and therapeutic regimens against chronic HBV infection. Chronic HBV patients cannot induce sufficient immune responses against the virus. HBV and its antigens are believed to suppress immune responses during chronic infection. Hence, studying the role of HBV in immune suppression is very important for the development of alternative therapeutic strategies for HBV infections.     

Ultrasonographic assessment of liver fibrosis with computer-assisted analysis of liver surface irregularities

PurposeThe goal of this study was to evaluate the diagnostic accuracy of a software program that automatically analyzes the liver surface to diagnose significant fibrosis, by comparing it to the subjective analysis of a radiologist and to transient elastography (Fibroscan^®).Patients and methodsOne hundred fourteen patients with chronic liver disease were included in the study. They underwent liver biopsy, FibroScan^® and ultrasonographic examination of the liver surface. The liver surface was analyzed by a software program that gave a score of surface irregularities. This evaluation was compared to subjective analysis by a radiologist expert in liver imaging and by two general radiologists.ResultsFifty percent of the patients had significant fibrosis according to the METAVIR score. The AUROC for the diagnosis of significant fibrosis by the software program was 0.80 (95%CI: 0.71–0.87), which was equivalent (P = 0.86) to that of FibroScan^® (0.81; 95%CI: 0.71–0.89). Results of the subjective analysis by the expert radiologist were poorer than those of the software analysis (P = 0.02) (AUROC = 0.66; 95%CI: 0.56–0.75). Interobserver agreement among radiologists was poor (0.25 < kappa < 0.37).ConclusionComputer-assisted liver surface analysis was better than subjective analysis, and similar to that of the FibroScan^®. This method could be useful for the diagnosis of significant fibrosis in patients with chronic hepatitis and complementary to the other non-invasive diagnostic tests.     

Prevalence of National Responsiveness to HBV Vaccine After 22 Years of Iranian Expanded Program on Immunization (EPI): A Systematic Review and Meta-Analysis Study

Context:

Hepatitis B Virus expanded program on immunization (EPI) started on 1993 in Iran. Most surveys have assessed the level of response to vaccine by measuring the titers of anti-HBs. This meta- analysis aimed to summarize the Iranian published data on the rate of vaccine-responders versus non-responders. Moreover, the impact of variables such as age, gender, type of vaccine, etc. on the levels of responsiveness was evaluated.

Evidence Acquisition:

All published papers on this topic in Iranian and international journals with affiliation of “Iran” were reviewed using standard keywords up to 2014. We included our study to healthy participants with no previous HBV infection and who had already received a complete course of HB vaccine. The estimated prevalence and 95% confidence intervals in 28 eligible articles for HBV vaccine responders (anti-HBs > 10 IU/mL) and non-responders (10 <) were analyzed by random effect method due to between-study heterogeneity.

Results:

The age of subjects was between 6 months and 15 years old. Overall, 5991 (51.5%) were male and 4571 (48.5%) females. Overall, 80% were responders to vaccine versus 20% nonresponders. With increase in age, the number of responders to vaccine decreased significantly (P = 0.001). There was no strong difference between responders versus nonresponders to vaccine for gender, types of vaccine, ethnicity and living area.

Conclusions:

The results arose from this meta-analysis highlighted the safety of vaccine and its effectiveness in stimulating immune response of vaccines, despite being different in generation, manufacturers and types. Moreover, there was no substantial difference between Iranian and other international investigations in the rate of nonresponsiveness to HBV vaccine.     

结直肠癌肝转移与乙肝病毒性肝炎及肝硬化关系研究进展

【摘要】〓结直肠癌为人体最常见恶性肿瘤之一,而结直肠癌肝转移为致死致残的主要原因。多方临床分析证实乙型病毒性肝炎、肝硬化患者结直肠癌肝转移发生率较正常患者明显降低,且有统计学意义。目前仍无明确机制解释该临床现象,本文从临床分析结果出发,以肿瘤微环境、肿瘤免疫、表观遗传学为主,综述乙型病毒性肝炎、肝硬化患者结肠癌肝转移率低的相关可能机制,并作进一步机制讨论。     

HBV感染对肝内胆管癌预后的影响

摘要：目的：探讨HBV感染对肝内胆管癌的预后影响。方法：回顾性分析了162例肝内胆管癌患者的临床资料,比较HBV感染和非HBV感染患者两组的预后有无差别。结果：HBV感染及非HBV感染两组患者中位生存期分别26月、28月;1年、3年、5年生存率分别为80%、29.8%、14.5%,79.3%、31.2%、16.6%,差异无统计学意义（P＝0.487）。两组患者无进展生存率差异亦无统计学意义（P＝0.634）。其中,HBV感染组不同HBV-DNA水平患者（HBV-DNA＜50IU/ml、HBV-DNA＞50IU/ml）其中位生存期的差异无统计学意义（P=0.643）,无进展生存率的差异亦无统计学意义（P=0.535）。经过COX多因素分析后,显示TNM分期IV期（HR：3.12; 95%CI ：1.57-6.20;P=0.001）、根治性手术（HR：0.47; 95%CI ：0.26-0.87;P=0.016）、淋巴结转移（HR：2.10; 95%CI：1.31-3.36;P=0.002）是影响总体生存时间的独立影响因素。结论：HBV感染对肝内胆管癌预后无显著性影响,根治性手术是肝内胆管癌预后的独立保护性因素,TNM分期IV期、淋巴结转移是影响总体生存时间的独立危险因素。