On the basis of the successful establishment of an animal model in tree shrews experimentally in fected with human hepatitis B virus (HHBV), a study on the hepatocarcinogenic effects of HHBV and aflatoxin B1 (AFB1) by...On the basis of the successful establishment of an animal model in tree shrews experimentally in fected with human hepatitis B virus (HHBV), a study on the hepatocarcinogenic effects of HHBV and aflatoxin B1 (AFB1) by using this animal model was conducted through a lifelong experiment. Among 41 tree shrews exposed to AFB1, 17 were experimentally infected by HHBV and 24 were uninfected. After 158 weeks, significant difference of primary liver cancer (PLC) incidence was present between the HHBV infected (52.94%) and uninfected (12.5%) groups (p<0.05). No difference was found between these two groups in the amount of AFB4 ingestion. Moreover, 1/9 of the tree shrews infected only by HHBV but not exposed to AFB4 developed PLC. No PLC was found in 6 tree shrews that had neither been infected with HHBV nor been exposed to AFB4. These results suggest the possible etiologic relationship between HHBV infection and PLC, as well as the synergetic effects of HHBV and AFB4 during PLC development.展开更多
The clinical course of infections with the hepatitis B virus (HBV) substantially varies between individuals, as a consequence of a complex interplay between viral, host, environmental and other factors. Due to the hig...The clinical course of infections with the hepatitis B virus (HBV) substantially varies between individuals, as a consequence of a complex interplay between viral, host, environmental and other factors. Due to the high genetic variability of HBV, the virus can be categorized into different HBV genotypes and subgenotypes, which considerably differ with respect to geographical distribution, transmission routes, disease progression, responses to antiviral therapy or vaccination, and clinical outcome measures such as cirrhosis or hepatocellular carcinoma. However, HBV (sub)genotyping has caused some controversies in the past due to misclassifications and incorrect interpretations of different genotyping methods. Thus, an accurate, holistic and dynamic classification system is essential. In this review article, we aimed at highlighting potential pitfalls in genetic and phylogenetic analyses of HBV and suggest novel terms for HBV classification. Analyzing full-length genome sequences when classifying genotypes and subgenotypes is the foremost prerequisite of this classification system. Careful attention must be paid to all aspects of phylogenetic analysis, such as bootstrapping values and meeting the necessary thresholds for (sub)genotyping. Quasi-subgenotype refers to subgenotypes that were incorrectly suggested to be novel. As many of these strains were misclassified due to genetic differences resulting from recombination, we propose the term “recombino-subgenotype”. Moreover, immigration is an important confounding facet of global HBV distribution and substantially changes the geographic pattern of HBV (sub)genotypes. We therefore suggest the term “immigro-subgenotype” to distinguish exotic (sub)genotypes from native ones. We are strongly convinced that applying these two proposed terms in HBV classification will help harmonize this rapidly progressing field and allow for improved prophylaxis, diagnosis and treatment.展开更多
AIM:To analyze the hepatitis B virus(HBV) characters in China,as well as the correlation between several HBV mutation and hepatitis symptoms.METHODS:A total of 1148 HBV genome sequences from patients throughout China ...AIM:To analyze the hepatitis B virus(HBV) characters in China,as well as the correlation between several HBV mutation and hepatitis symptoms.METHODS:A total of 1148 HBV genome sequences from patients throughout China were collected via the National Center For Biotechnology Information database(information including:genotype,territory and clinical status).HBV genotypes were classified by a direct reference from the Genbank sequence annotation,phylogenetic tree and online software analysis(http://www.ncbi.nlm.nih.gov/projects/genotyping/formpage.cgi).The phylogenetic tree was constructed based on the neighbor-joining method by MEGA5.0 software.HBV sequences were grouped based on phylogenetic tree and the distance between the groups was calculated by using the computer between group mean distance methods.Seven hundred and twelve HBV sequences with clear annotation of clinical symptoms were selected to analyses the correlation of mutation and clinical symptoms.Characteristics of sequences were analyzed by using DNAStar and BioEdit software packages.The codon usage bias and RNA secondary structures analysis were performed by RNAdraw software.Recombination analysis was performed by using Simplot software.RESULTS:In China,HBV genotype C was the predominant in Northeastern,genotype B was predominant in Central Southern areas,genotype B and C were both dominant in Southwestern areas,and the recombinant genotype C/D was predominant in Northwestern areas.C2 and B2 were identified as the two major sub-genotypes,FJ386674 might be a putative sub-genotype as B10.The basal core promoter double mutation and pre-C mutation showed various significant differences between hepatitis symptoms.In addition to ATG,many other HBV initiation codons also exist.HBV has codon usage bias;the termination codon of X,C and P open reading frames(ORF) were TAA,TAG,and TGA,respectively.The major stop codons of S-ORF were TAA(96.45%) and TGA(83.60%) in B2 and C2 subtype,respectively.CONCLUSION:This study recapitulated the epidemiology of HBV in China,and the information might be meaningful critical for the future prevention and therapy of HBV infections.展开更多
OBJECTIVE: To detect the expression and variation of the p53 gene in hepatocarcinogenesis of tree shrews induced by hepatitis B virus (HBV) and aflatoxin B_1(AFB_1). METHODS: Tree shrews were divided into four groups:...OBJECTIVE: To detect the expression and variation of the p53 gene in hepatocarcinogenesis of tree shrews induced by hepatitis B virus (HBV) and aflatoxin B_1(AFB_1). METHODS: Tree shrews were divided into four groups: group A, infected with HBV and fed with AFB_1; group B, only infected with HBV; group C, fed with AFB_1 alone; and group D normal control. The tree shrews underwent liver biopsy every. 15 weeks. Liver and tumor tissues were detected by immunohistochemistry and molecular biotechnologies. RESULTS: The incidence of hepatocellular carcinoma (HCC) was higher in group A (66.7%) than in groups B (0) and C (30%). HCC occurrence was earlier in group A than in group C (120.0±16.6 wk vs 153.3±5.8 wk, t=3.336, P<0.01). Mutated p53 protein was not found in all groups before 75 weeks of experiment. At the 105th week, the expression rates of mutated p53 protein were 78.6%, 60.0% and 71.4% in groups A, B and C respectively, which were significantly higher than that in group D (10%) (X^2≥5.03, P<0.05). An abnormal band of the p53 gene was detected in groups A and C. The mutational points of the p53 gene in liver cancer of tree shrews were at codon 275, 78 and 13. Nucleotide sequence and amino acids sequence of tree shrew's wild-type p53 were 91.7% and 93.4% in homology, compared with those of human p53, respectively. CONCLUSIONS: Remarkable synergistic effect on HCC exists between HBV and AFB_1. Mutated p53 protein expressed before occurrence of HCC promotes the development of HCC. HBV and AFB_1 may synergistically induce p53 gene mutation.展开更多
Objective: To assess the efficacy of Yanggan Aoping Mixture (养肝澳平, YGAPM) in treatinghepatitis B. Methods: Patients suffered from chronic hepatitis B were treated with YGAPM. Observe theirshort-- and long--term ef...Objective: To assess the efficacy of Yanggan Aoping Mixture (养肝澳平, YGAPM) in treatinghepatitis B. Methods: Patients suffered from chronic hepatitis B were treated with YGAPM. Observe theirshort-- and long--term efficacy and the change of serum hepatitis B virus marker. In experiment, the effects ofYGAPM in treating rat's liver injury as well as HBV--infected tree shrew and duck HBV--infected ducks were observed. Results: In 79 cases of chronic persistent hepatitis, the markedly effective rate was 60. 76%, and further raised to 70. 00 % in follow-up study in 40 cases. In 73 cases of chronic active hepatitis, the markedly effective rate was 60. 27%, and further raised to 62. 50% in 32 follow-up cases. In the treatment group, 85 of the119 cases (71. 43 % ) with HBeAg-positive were converted to negative. Whereas in the control group, only 40 of89 HBeAg-positive cases (44. 94 % ) were converted to negative, P < 0. 01. Results of experimental studyshowed that negative conversion rate of tree shrew infected with HBV marker was raised, while the duck HBVDNA in infected duck blood was inhibited. Those compared with the control group separately, the differencewas markedly significant. Conclusion: YGAPM is an effective drug in treating chronic hepatitis B, and it couldeffectively convert the marker to negative.展开更多
文摘On the basis of the successful establishment of an animal model in tree shrews experimentally in fected with human hepatitis B virus (HHBV), a study on the hepatocarcinogenic effects of HHBV and aflatoxin B1 (AFB1) by using this animal model was conducted through a lifelong experiment. Among 41 tree shrews exposed to AFB1, 17 were experimentally infected by HHBV and 24 were uninfected. After 158 weeks, significant difference of primary liver cancer (PLC) incidence was present between the HHBV infected (52.94%) and uninfected (12.5%) groups (p<0.05). No difference was found between these two groups in the amount of AFB4 ingestion. Moreover, 1/9 of the tree shrews infected only by HHBV but not exposed to AFB4 developed PLC. No PLC was found in 6 tree shrews that had neither been infected with HHBV nor been exposed to AFB4. These results suggest the possible etiologic relationship between HHBV infection and PLC, as well as the synergetic effects of HHBV and AFB4 during PLC development.
基金Supported by Mahmoud Reza Pourkarim is supported by a postdoctoral grant from the''Fonds voor Wetenschappelijk Onderzoek Vlaanderen''
文摘The clinical course of infections with the hepatitis B virus (HBV) substantially varies between individuals, as a consequence of a complex interplay between viral, host, environmental and other factors. Due to the high genetic variability of HBV, the virus can be categorized into different HBV genotypes and subgenotypes, which considerably differ with respect to geographical distribution, transmission routes, disease progression, responses to antiviral therapy or vaccination, and clinical outcome measures such as cirrhosis or hepatocellular carcinoma. However, HBV (sub)genotyping has caused some controversies in the past due to misclassifications and incorrect interpretations of different genotyping methods. Thus, an accurate, holistic and dynamic classification system is essential. In this review article, we aimed at highlighting potential pitfalls in genetic and phylogenetic analyses of HBV and suggest novel terms for HBV classification. Analyzing full-length genome sequences when classifying genotypes and subgenotypes is the foremost prerequisite of this classification system. Careful attention must be paid to all aspects of phylogenetic analysis, such as bootstrapping values and meeting the necessary thresholds for (sub)genotyping. Quasi-subgenotype refers to subgenotypes that were incorrectly suggested to be novel. As many of these strains were misclassified due to genetic differences resulting from recombination, we propose the term “recombino-subgenotype”. Moreover, immigration is an important confounding facet of global HBV distribution and substantially changes the geographic pattern of HBV (sub)genotypes. We therefore suggest the term “immigro-subgenotype” to distinguish exotic (sub)genotypes from native ones. We are strongly convinced that applying these two proposed terms in HBV classification will help harmonize this rapidly progressing field and allow for improved prophylaxis, diagnosis and treatment.
基金Supported by National Natural Science Foundation of China,No.81160352grants from the Education Department Foundation of Yunnan Province,No.2012J091+1 种基金Health Bureau of Yunnan Province,No.D-201203(partly)Science and Technology Department of Yunnan Province,No.2013HB084(partly)
文摘AIM:To analyze the hepatitis B virus(HBV) characters in China,as well as the correlation between several HBV mutation and hepatitis symptoms.METHODS:A total of 1148 HBV genome sequences from patients throughout China were collected via the National Center For Biotechnology Information database(information including:genotype,territory and clinical status).HBV genotypes were classified by a direct reference from the Genbank sequence annotation,phylogenetic tree and online software analysis(http://www.ncbi.nlm.nih.gov/projects/genotyping/formpage.cgi).The phylogenetic tree was constructed based on the neighbor-joining method by MEGA5.0 software.HBV sequences were grouped based on phylogenetic tree and the distance between the groups was calculated by using the computer between group mean distance methods.Seven hundred and twelve HBV sequences with clear annotation of clinical symptoms were selected to analyses the correlation of mutation and clinical symptoms.Characteristics of sequences were analyzed by using DNAStar and BioEdit software packages.The codon usage bias and RNA secondary structures analysis were performed by RNAdraw software.Recombination analysis was performed by using Simplot software.RESULTS:In China,HBV genotype C was the predominant in Northeastern,genotype B was predominant in Central Southern areas,genotype B and C were both dominant in Southwestern areas,and the recombinant genotype C/D was predominant in Northwestern areas.C2 and B2 were identified as the two major sub-genotypes,FJ386674 might be a putative sub-genotype as B10.The basal core promoter double mutation and pre-C mutation showed various significant differences between hepatitis symptoms.In addition to ATG,many other HBV initiation codons also exist.HBV has codon usage bias;the termination codon of X,C and P open reading frames(ORF) were TAA,TAG,and TGA,respectively.The major stop codons of S-ORF were TAA(96.45%) and TGA(83.60%) in B2 and C2 subtype,respectively.CONCLUSION:This study recapitulated the epidemiology of HBV in China,and the information might be meaningful critical for the future prevention and therapy of HBV infections.
基金This study was supported by a grant from the National Natural Science Foundation of China(No. 39260033)and a grant from Guangxi Science Foundation, China (No. 0143058).
文摘OBJECTIVE: To detect the expression and variation of the p53 gene in hepatocarcinogenesis of tree shrews induced by hepatitis B virus (HBV) and aflatoxin B_1(AFB_1). METHODS: Tree shrews were divided into four groups: group A, infected with HBV and fed with AFB_1; group B, only infected with HBV; group C, fed with AFB_1 alone; and group D normal control. The tree shrews underwent liver biopsy every. 15 weeks. Liver and tumor tissues were detected by immunohistochemistry and molecular biotechnologies. RESULTS: The incidence of hepatocellular carcinoma (HCC) was higher in group A (66.7%) than in groups B (0) and C (30%). HCC occurrence was earlier in group A than in group C (120.0±16.6 wk vs 153.3±5.8 wk, t=3.336, P<0.01). Mutated p53 protein was not found in all groups before 75 weeks of experiment. At the 105th week, the expression rates of mutated p53 protein were 78.6%, 60.0% and 71.4% in groups A, B and C respectively, which were significantly higher than that in group D (10%) (X^2≥5.03, P<0.05). An abnormal band of the p53 gene was detected in groups A and C. The mutational points of the p53 gene in liver cancer of tree shrews were at codon 275, 78 and 13. Nucleotide sequence and amino acids sequence of tree shrew's wild-type p53 were 91.7% and 93.4% in homology, compared with those of human p53, respectively. CONCLUSIONS: Remarkable synergistic effect on HCC exists between HBV and AFB_1. Mutated p53 protein expressed before occurrence of HCC promotes the development of HCC. HBV and AFB_1 may synergistically induce p53 gene mutation.
文摘Objective: To assess the efficacy of Yanggan Aoping Mixture (养肝澳平, YGAPM) in treatinghepatitis B. Methods: Patients suffered from chronic hepatitis B were treated with YGAPM. Observe theirshort-- and long--term efficacy and the change of serum hepatitis B virus marker. In experiment, the effects ofYGAPM in treating rat's liver injury as well as HBV--infected tree shrew and duck HBV--infected ducks were observed. Results: In 79 cases of chronic persistent hepatitis, the markedly effective rate was 60. 76%, and further raised to 70. 00 % in follow-up study in 40 cases. In 73 cases of chronic active hepatitis, the markedly effective rate was 60. 27%, and further raised to 62. 50% in 32 follow-up cases. In the treatment group, 85 of the119 cases (71. 43 % ) with HBeAg-positive were converted to negative. Whereas in the control group, only 40 of89 HBeAg-positive cases (44. 94 % ) were converted to negative, P < 0. 01. Results of experimental studyshowed that negative conversion rate of tree shrew infected with HBV marker was raised, while the duck HBVDNA in infected duck blood was inhibited. Those compared with the control group separately, the differencewas markedly significant. Conclusion: YGAPM is an effective drug in treating chronic hepatitis B, and it couldeffectively convert the marker to negative.
