May 2014, Volume 8 Issue 2

Cover illustration

  • SA-β-gal staining detection of cisplatin-treated hepatoma cells. The positive SA-β-gal staining was exhibited in the cytoplasm of these cells and accompanied by long-term cisplatin treatment. (Courtesy of Dr. Chang Liu. See Pages 227-235 by Kai Qu et al. for more information.)

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    Ke-Qin Hu
    Yong-Yuan Zhang,Ke-Qin Hu,Zhongping Duan

    Chronic hepatitis B virus (HBV) infection is a significant threat to public health and an enormous burden on society. Mechanisms responsible for chronic HBV infection remain poorly understood. A better understanding of the natural course of chronic HBV infection may shed new light on the mechanisms underlying this disease and help in designing new antiviral strategies. Natural course of chronic HBV infection is conventionally viewed as an uninterrupted process that is usually marked by HBV e antigen (HBeAg) seroconversion or characterized by different phases associated with assumed host responses to HBV infection. However, none of these descriptions captures or highlights the core events that determine the natural course of chronic HBV infection. In this review, we briefly present the current knowledge on this subject and explain the significance and implication of events that occur during infection. A pre-core mutant becomes predominant in the viral population following elimination of the wild-type virus in duck hepatitis B virus-chronically infected animals. The coupled events in which first there is viral clearance that clears wild-type virus and then there is the reinfection of wild-type virus cleared livers with mutant virus are highly relevant to understanding of the natural course of chronic HBV infection under both treated and untreated conditions. In our new perspective, a general natural course of chronic HBV infection comprises cycles of viral clearance and reinfection, and such cycles prolong the chronic HBV infection course. Reviewing published data on the natural course of chronic HBV infection can reduce the possibility of missing important points in the initial data interpretation.

    Zhangguo Chen,Jing H. Wang

    Activation-induced deaminase (AID) initiates the secondary antibody diversification process in B lymphocytes. In mammalian B cells, this process includes somatic hypermutation (SHM) and class switch recombination (CSR), both of which require AID. AID induces U:G mismatch lesions in DNA that are subsequently converted into point mutations or DNA double stranded breaks during SHM/CSR. In a physiological context, AID targets immunoglobulin (Ig) loci to mediate SHM/CSR. However, recent studies reveal genome-wide access of AID to numerous non-Ig loci. Thus, AID poses a threat to the genome of B cells if AID-initiated DNA lesions cannot be properly repaired. In this review, we focus on the molecular mechanisms that regulate the specificity of AID targeting and the repair pathways responsible for processing AID-initiated DNA lesions.

    Du Yan, Han Xue, Pu Rui, Xie Jiaxin, Zhang Yuwei, Cao Guangwen

    This study was designed to investigate the contribution of miRNA-122-binding site polymorphism at the IL-1A gene and its multiplicative interactions with hepatitis B virus (HBV) mutations in the risk of hepatocellular carcinoma (HCC). A total of 1021 healthy controls, 302 HBV surface antigen (HBsAg) seroclearance subjects, and 2011 HBsAg-positive subjects (including 1021 HCC patients) were enrolled in this study. Quantitative PCR was used to genotype rs3783553. HBV mutations were determined by direct sequencing. Multivariate logistic regression analyses were performed to test the associations of rs3783553, mutations, and their interactions with the risk of HCC. No significant association was found between rs3783553 and the risk of HCC among healthy controls, HBsAg seroclearance subjects, HBsAg-positive subjects without HCC, and all controls. Additionally, rs3783553 was not significantly associated with chronic HBV infection, liver cirrhosis, HBV e antigen seroconversion, abnormal alanine aminotransferase, and high viral load (>104 copies/ml). However, the TTCA insertion allele of rs3783553 was significantly associated with an increased frequency of HBV C7A mutation compared with homozygous TTCA deletion carriers [(del/ins+ ins/ins) vs. del/del, adjusted odds ratio (OR)=1.48, 95% confidence interval (CI)=1.09-2.02, P=0.013]. Multiplicative interaction of rs3783553 with HBV preS deletion significantly reduced the risk of HCC in males, with an adjusted OR of 0.64 (95% CI=0.42-0.98; P=0.041) after age and HBV genotype were adjusted. Although rs3783553 did not significantly affect genetic susceptibility to HBV-related HCC, its variant allele may predispose the host to selecting HBV C7A mutation during evolution and significantly reduce the risk of HCC caused by HBV preS deletion. This study provides an insight into the complex host-virus interaction in HBV-induced hepatocarcinogenesis and is helpful in determining HBsAg-positive subjects who are likely to develop HCC.

    Kai Qu,Ting Lin,Zhixin Wang,Sinan Liu,Hulin Chang,Xinsen Xu,Fandi Meng,Lei Zhou,Jichao Wei,Minghui Tai,Yafeng Dong,Chang Liu

    Accelerated senescence is important because this process is involved in tumor suppression and has been induced by many chemotherapeutic agents. The platinum-based chemotherapeutic agent cisplatin displays a wide range of antitumor activities. However, the molecular mechanism of cisplatin-induced accelerated senescence in hepatocellular carcinoma (HCC) remains unclear. In the present study, the growth inhibitory effect of cisplatin on HepG2 and SMMC-7721 cells was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cellular senescence was then assessed by β-galactosidase assay. Senescence-related factors, including p53, p21, and p16, were evaluated by quantitative reverse transcription-polymerase chain reaction. Reactive oxygen species (ROS) was analyzed by flow cytometry. Our results revealed that cisplatin reduced the proliferation of HepG2 and SMMC-7721 cells in a dose- and time-dependent manner. Senescent phenotype observed in cisplatin-treated hepatoma cells was dependent on p53 and p21 activation but not on p16 activation. Furthermore, cisplatin-induced accelerated senescence depended on intracellular ROS generation. The ROS scavenger N-acetyl-L-cysteine also significantly suppressed the cisplatin-induced senescence of HepG2 and SMMC-7721 cells. In conclusion, our results revealed a functional link between intracellular ROS generation and cisplatin-induced accelerated senescence, and this link may be used as a potential target of HCC.

    Hang Zhou,Yao Jia,Jian Shen,Shaoshuai Wang,Xiong Li,Ru Yang,Kecheng Huang,Ting Hu,Fangxu Tang,Jin Zhou,Jingping Yuan,Lei Huang,Xun Tian,Zhilan Chen,Qinghua Zhang,Changyu Wang,Ling Xi,Dongrui Deng,Hui Wang,Ding Ma,Shuang Li

    This study aimed to analyze the prevalence of bacterial, Candida, Trichomonas, and human papillomavirus (HPV) infections in ThinPrep cytological test (TCT) performed on women of Wuhan, China. ThinPrep smears were screened by two independent experienced pathologists and reported from 2008 to 2010. A total of 46 866 ThinPrep smears were studied, and smears with inflammation were analyzed. Of the 44 162 enrolled patients, inflammation changes were observed in 21 935 (49.7%) and specific infections in 6884 (31.4%). The infections detected were as follows: bacteria, 5663 (82.3%); Candida, 825 (12.0%); Trichomonas, 273 (4.0%); and HPV, 148 (2.1%). Significant changes were found in the prevalence of bacteria and Candida among women who underwent TCT before and after 2010. χ2 revealed an increasing proportion of specific infections found in smears after 2010 (P=0.000). In conclusion, bacterial infection was the most detectable in the ThinPrep smears, followed by Candida and Trichomonas. The prevalence of infection identified by TCT was found to be similar in previous literature in China.

    Jiangang Pan,Mo Liu,Xing Zhou

    Approximately 70% of newly diagnosed bladder tumors are non-muscle invasive bladder cancer (NMIBC). NMIBC accounts for approximately 80% of total bladder cancer cases. Bacillus Calmette-Guérin (BCG) instillation and maintenance is considered as the standard adjuvant treatment for superficial bladder cancer. A number of randomized studies have focused on the benefit of maintenance therapy following initial BCG induction. To provide further insights into the effect of intravesical instillation on recurrence in patients with NMIBC, we analyzed this relationship by conducting an updated detailed meta-analysis. Evidence suggested that adjuvant intravesical BCG with maintenance treatment is significantly effective for the prophylaxis of tumor recurrence in patients with NMIBC.

    Lei Li,Yimei Liu,Tiancheng Luo,Jian Zhou,Yingyong Hou,Xizhong Shen,Jiyao Wang

    The clinical data of a patient with acute-on-chronic liver failure were analyzed retrospectively. The patient has suffered from hepatitis B for 30 years. His liver function deteriorated, yielding Child-Pugh grade C and reaching a model for end-stage liver disease score of 33 points within a short period; this condition was complicated with highly active variceal bleeding and coagulation system failure (PT > 100 s). The patient also presented hepatocellular carcinoma. Comprehensive treatments included effective inhibition of hepatitis B virus replication and intensive care support. Piggyback orthotopic liver transplantation was performed as the final treatment. The patient recovered uneventfully and was discharged after surgery.

    Muhammad Furqan,Yamei Chen,Akintunde Akinleye,Judy Sarungbam,Alan Gass,Karen Seiter,Delong Liu

    Mantle cell lymphoma is an aggressive subtype of B cell non-Hodgkin lymphoma. It can progress to leukemic phase but frank leukemic picture at initial presentation is not common. Leukemic phase indicates advance stage of the disease and generally associated with extensive extra-nodal involvement. Pericardial invasion has been reported, however we could not find a report of myocardial infiltration by this disease since the appraisal of the term “mantle cell lymphoma” in 1992. Here we report a case of cardiac involvement by mantle cell leukemia leading to cardiogenic shock which complicates the treatment decisions.

    Hui Li,Ran Li,Jiuxin Qu,Xiaomin Yu,Zhixin Cao,Yingmei Liu,Bin Cao

    Although significant breakthroughs have been achieved in tuberculosis management, we still encounter numerous difficulties in diagnosis and treatment of the disease. Additionally, a new challenge, multidrug-resistant tuberculosis (MDR-TB) with unspecific clinical presentation, often results in delayed diagnosis. In this paper, we reported a case of disseminated tuberculosis with rare presentation of ventricular fibrillation, which proved resistant to both isoniazid and rifampicin. A review of literature showed that ventricular fibrillation or tachycardia in tuberculosis patients with pericarditis or myocarditis has been sporadically reported in the past, but none has been conducted involving patients with MDR-TB infections.