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Chronic hepatitis B virus infection: epidemiology, prevention, and treatment in China
Rui Yu, Rong Fan, Jinlin Hou
Front. Med.. 2014, 8 (2 ): 135-144.
https://doi.org/10.1007/s11684-014-0331-5
Chronic hepatitis B is a major health problem in China. The universal vaccination program since 1992 has changed the epidemiology of hepatitis B virus infection in China from highly to moderately endemic. The most prevalent hepatitis B virus strains in China are genotypes B and C, whereas those in western provinces are genotypes D and C/D hybrid. Chronic hepatitis B poses a heavy burden to the society in China. Different treatment strategies have been explored to improve patient outcomes in a cost-effective manner. However, antiviral drugs with a low genetic barrier to resistance are still extensively used because of the generally low income and limited resources in China. Individualized antiviral therapy is closely associated with translational medicine, which utilizes information from studies on genomics, immune biomarkers, and fibrosis. The results of these studies are crucial in further improving treatment outcomes.
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Current recommendations of managing HBV infection in preconception or pregnancy
James S. Park, Calvin Pan
Front. Med.. 2014, 8 (2 ): 158-165.
https://doi.org/10.1007/s11684-014-0340-4
Hepatitis B remains a leading cause of cirrhosis, hepatocellular carcinoma and liver transplantation worldwide. Management of chronic hepatitis B during pregnancy is challenging. Transmission of hepatitis B to infants still occurs perinatally although immunoprophylaxis is widely available for infants born to mothers with chronic hepatitis B infection. The emerging data suggest that initiation of antiviral therapy in the beginning of the third trimester in highly viremic mothers can prevent immunoprophylaxis failure in their infants. The available drug safety data show that lamivudine, telbivudine and tenofovir are generally safe to be used during the pregnancy. In order to minimize the fetal exposure to the antiviral medication, antiviral therapy during the pregnancy should be limited to a selected group of patients with cirrhosis, high hepatitis B viral load, or prior history immunoprophylaxis failure. An elective Caesarean section may reduce the risk of perinatal transmission. For those females planning for pregnancy or in early stage of pregnancy, communication and follow-up among obstetrician, gastroenterologist, and primary care physician are important. In this article, we will review the features of hepatitis B infection before, during and after the pregnancy; the risk factors that increase mother-to-child transmission; safety data on antiviral drug use during pregnancy; and the potential role of Caesarean section in selected cases.
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Advances in managing hepatocellular carcinoma
Marielle Reataza, David K. Imagawa
Front. Med.. 2014, 8 (2 ): 175-189.
https://doi.org/10.1007/s11684-014-0332-4
Multiple modalities for treatment of hepatocellular carcinoma are available, depending on tumor size and number. Surgical resection remains the gold standard, so long as the residual liver function reserve is sufficient. In patients with advanced cirrhosis, liver transplantation is the preferred option, as these patients may not have adequate hepatic reserve after resection. Salvage liver transplantation has also become an option for a select few patients who recur after surgical resection. Ablative techniques have been used for palliation as well as to either completely destroy the tumor, act as an adjunct to resection, or downstage the tumor to meet Milan criteria such that a patient may be a candidate for liver transplantation. Radiofrequency ablation, microwave ablation, chemoembolization, radioembolization, and irreversible electroporation have all been used in this capacity. Currently, sorafenib is the only US Food and Drug Administration-approved chemotherapeutic for hepatocellular carcinoma. The efficacy of sorafenib, in combination with other agents, transarterial chemoembolization, and surgical resection is currently being investigated. Sunitinib and brivanib, tyrosine kinase inhibitors, have failed as potential first- or second-line options for chemotherapy. Bevacizumab in combination with erlotinib is also currently being studied. Final analysis for ramucirumab and axitinib are pending. Tivantinib, a selective mesenchymal-epithelial transition factor (MET) inhibitor, is also undergoing clinical trials for efficacy in MET-high tumors. This review serves to emphasize the current and new technologies emerging in the treatment of hepatocellular carcinoma.
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The regulatory sciences for stem cell-based medicinal products
Bao-Zhu Yuan, Junzhi Wang
Front. Med.. 2014, 8 (2 ): 190-200.
https://doi.org/10.1007/s11684-014-0323-5
Over the past few years, several new achievements have been made from stem cell studies, many of which have moved up from preclinical stages to early, or from early to middle or late, stages thanks to relatively safe profile and preliminary evidence of effectiveness. Moreover, some stem cell-based products have been approved for marketing by different national regulatory authorities. However, many critical issues associated mainly with incomplete understanding of stem cell biology and the relevant risk factors, and lack of effective regulations still exist and need to be urgently addressed, especially in countries where establishment of appropriate regulatory system just commenced. More relevantly, the stem cell regulatory sciences need to be established or improved to more effectively evaluate quality, safety and efficacy of stem cell products, and for building up the appropriate regulatory framework. In this review, we summarize some new achievements in stem cell studies, especially the preclinical and clinical studies, the existing regulations, and the associated challenges, and we then propose some considerations for improving stem cell regulatory sciences with a goal of promoting the steadfast growth of the well-regulated stem cell therapies abreast of evolvement of stem cell sciences and technologies.
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Association of miRNA-122-binding site polymorphism at the interleukin-1 α gene and its interaction with hepatitis B virus mutations with hepatocellular carcinoma risk
Du Yan, Han Xue, Pu Rui, Xie Jiaxin, Zhang Yuwei, Cao Guangwen
Front. Med.. 2014, 8 (2 ): 217-226.
https://doi.org/10.1007/s11684-014-0326-2
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.
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Reactive oxygen species generation is essential for cisplatin-induced accelerated senescence in hepatocellular carcinoma
Kai Qu,Ting Lin,Zhixin Wang,Sinan Liu,Hulin Chang,Xinsen Xu,Fandi Meng,Lei Zhou,Jichao Wei,Minghui Tai,Yafeng Dong,Chang Liu
Front. Med.. 2014, 8 (2 ): 227-235.
https://doi.org/10.1007/s11684-014-0327-1
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.
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Gynecologic infections seen in ThinPrep cytological test in Wuhan, China
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
Front. Med.. 2014, 8 (2 ): 236-240.
https://doi.org/10.1007/s11684-014-0322-6
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.
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Ventricular tachycardia in a disseminated MDR-TB patient: a case report and brief review of literature
Hui Li,Ran Li,Jiuxin Qu,Xiaomin Yu,Zhixin Cao,Yingmei Liu,Bin Cao
Front. Med.. 2014, 8 (2 ): 259-263.
https://doi.org/10.1007/s11684-014-0321-7
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.
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