Pathological Change of Chronic Hepatitis B Patients with Different Tongue Coatings by Circular Multi-Omics Integrated Analysis / 中国结合医学杂志

OBJECTIVE@#To compare the circular pathological changes of chronic hepatitis B (CHB) patients according to the tongue diagnosis.@*METHODS@#Totally 41 CHB patients with typical white tongue coating (WTC) or yellow tongue coating (YTC) were enrolled and 14 healthy volunteers with normal tongue manifestation served as controls. The mRNA expression of peripheral leukocytes was detected by GeneChips, and 9 genes were randomly selected for expression validation. Circular metabolites were detected by gas chromatographymass spectrometry. Biological information was analyzed based on ingenuity pathways analysis or metabolomics database and the integrated networks were constructed by ClueGO.@*RESULTS@#A total of 945 and 716 differentially expressed genes were found in patients with WTC and YTC relative to healthy volunteers respectively. The biological information analysis indicated that CHB patients had obviously increased functions in cell death, apoptosis and necrosis (Z-score ⩾2, P<0.05) and decreased activation in T lymphocytes (Z-score ⩽-2, P<0.05), regardless of the tongue manifestation. Compared to patients with WTC, the YTC patients were predicted to be more active in functions related to virus replication (Z-score ⩾2, P<0.05), and the content of circular fatty acids, such as oleic acid (P=0.098) and lauric acid (P=0.035), and citric acid cycle-related metabolites were higher in the YTC patients (P<0.1). The integrated analysis based on differential genes and metabolites indicated that the most difference in the biological function network between the WTC and YTC patients was tumor necrosis factor receptor associated factor 6 mediated-nuclear factor kappa-B activation process.@*CONCLUSIONS@#CHB patients with YTC had more severe inflammation and fatty acids metabolism aberrant than patients with WTC. The results facilitate the modern pathological annotation of Chinese medicine tongue diagnosis theory and provide a reference for the interpretation of pharmacological mechanisms of Chinese medicine treatment.

Chinese Herbal Medicine Combined with Entecavir for HBeAg Positive Chronic Hepatitis B: Study Protocol for a Multi-Center, Double-Blind Randomized-Controlled Trial / 中国结合医学杂志

<p><b>BACKGROUND</b>The domestic prevalence of chronic hepatitis B (CHB) in China is 7.18% in 2006, imposing great societal healthcare burdens. Nucleot(s)ide analogues (NUCs) anti-hepatitis B virus (HBV) therapies are widely applied despite the relatively low rate of seroconversion and high risk of drug-resistant mutation. More effective treatments for CHB deserve further explorations. Combined therapy of NUCs plus Chinese herbal medicine (CHM) is widely accepted in China, which is recognized as a prospective alternative approach. The study was primarily designed to confirm the hypothesis that Tiaogan-Yipi Granule (, TGYP) or Tiaogan-Jianpi-Jiedu Granule (, TGJPJD) plus entecavir tablet (ETV) was superior over ETV monotherapy in enhancing HBeAg loss rate.</p><p><b>METHODS</b>The study was a nationwide, large-scale, multi-center, double-blind, randomized, placebo-controlled trial with a designed duration of 108 weeks. A total of 16 hospitals and 596 eligible Chinese HBeAg positive CHB patients were enrolled from November 2012 to September 2013 and randomly allocated into 2 groups in 1:1 ratio via central randomization system: experimental group (EG) and control group (CG). Subjects in EG received CM formulae (TGYP or TGJPJD, 50 g per dose, twice daily) plus ETV tablet (or ETV placebo) 0.5 mg per day in the first 24 weeks (stage 1), and CHM granule plus ETV tablet (0.5 mg per day) from week 25 to 108 (stage 2). Subjects in CG received CHM Granule placebo plus ETV tablet (0.5 mg per day) for 108 weeks throughout the trial. The assessments of primary outcomes (HBV serum markers and HBV-DNA) were conducted by a third-party College of American Pathologists (CAP) qualified laboratory. Adverse effects were observed in the hospitals of recruitment.</p><p><b>DISCUSSION</b>The study was designed to compare the curative effect of CM plus ETV and ETV monotherapy in respect of HBeAg loss, which is recognized by the European Association for the Study of the Liver as "a valuable endpoint". We believe this trial could provide a reliable status for patients' "journey" towards durable responses after treatment discontinuation. The trial was registered before recruitment on Chinese Clinical trial registry (No. ChiCTR-TRC-12002784, Version 1.0, 2015/12/23).</p>

Correlation between Constitution of Yin Deficiency Syndrome and Polymorphism of HLA-DQA1/Treatment Response of Peg-IFNalpha Therapy in HBeAg Positive Chronic Hepatitis B Patients / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the correlation between constitution of yin deficiency syndrome (YDS) and polymorphism of HLA-DQA1/treatment response of Peg-lFNalpha therapy in HBeAg positive chronic hepatitis B (CHB) patients, and to explore constitution of Chinese medicine (CM) in response of interferon therapy.</p><p><b>METHODS</b>Totally 120 HBeAg positive CHB patients who were treated with Peg-IFNalpha were enrolled, and assigned to YDS group (59 cases) and non-YDS group (61 cases) according to classification of CM constitutions. All patients were subcutaneously injected with Peg-IFNalpha-2b (1.0 microg/kg body weight) or Peg-IFNalpha-2a (180 microg), once per week. Effective efficacy was primarily judged when complete response (CR) or partial response (PR) was obtained at month 6. Those with CR or PR completed 1 year therapeutic course. HLA-DQA1 gene types were detected by polymerase chain reaction sequence specific primers (PCR-SSP). The distribution difference of CM constitutions in patients with CR or PR and their inter-group HLA-DQA1 allele frequency were compared.</p><p><b>RESULTS</b>Different treatment responses of Peg-IFNalpha were observed in CHB patients of two different CM constitutions. The ratio of CR + PR was 61.0% (36/59) in YDS group, obviously lower than that in NYDS group [78.7% (48/61), P < 0. 05]. Patients with CR had a lower allele frequency of HLA-DQA1 * 0501 than those with no-response [14.8% (8/54) vs. 30.6% (22/72)] with statistical difference (P < 0.05). Patients with CR had a higher allele frequency of HLA-DQA1 * 0601 than those with no-response [18.5% (10/54) vs. 5.6% (4/72)] with statistical difference (P < 0.05). The allele frequency of HLA-DQA1 * 0301 was lower in YDS group than in non-YDS group [2. 5% (3/118) vs. 9.8% (12/122)] with statistical difference (P < 0.05). The allele frequency of HLA-DQA1 * 0501 was higher in YDS group than in non-YDS group [33.9% (40/118) vs. 18.9% (23/122)] with statistical difference (P < 0.05). Yet statistical significance was lost after adjustment (Pc > 0.05 for both).</p><p><b>CONCLUSIONS</b>Both constitutions of CM and HLA-DQA1 gene polymorphism af- fect HBeAg positive CHB patients' response to Peg-INFalpha. Constitutions of YDS and HLA-DQA1 * 0501 was not favorable to response, their association needed to be further studied.</p>

Clinical research of the relation of hepatitis B surface antigen (HBsAg) quantification and hepatic tissue pathological staging / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To explore the correlation of serum hepatitis B surface antigen (HBsAg) level and hepatic tissue pathological staging in the chronic hepatitis B infected persons.</p><p><b>METHODS</b>Collect the clinical data of 272 cases who are HBsAg-positive more than 6 months and accepted hepatic biopsy in our hospital. Detect serum HBsAg quantification, ALT, HBV DNA, complete blood count, hepatic tissue pathological staging, grouping the cases according to the stage of inflammation and the fibrosis degree respectively. Observe serum HBsAg quantification, HBV DNA and the stage of inflammation and the fibrosis degree. Analyse the correlation between HBsAg quantification and HBV DNA.</p><p><b>RESULTS</b>The correlation of serum HBsAg level and HBV DNA is notable. Serum HBsAg level is a variable affecting hepatic tissue pathological stage significantly.</p><p><b>CONCLUSIONS</b>Serum HBsAg level is a marker having higher specificity and sensitivity to diagnose the hepatic fibrosis.</p>

The relationship between serum HBsAg levels and liver inflammation and fibrosis in patients with chronic hepatitis B / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the relation of hepatitis B surface antigen (HBsAg) level with chronic hepatitis B (CHB) and liver inflammation and fibrosis.</p><p><b>METHODS</b>A total of 301 patients who diagnosed CHB and underwent liver biopsy were enrolled into the study. Meantimes, the biochemical markers, ferritin (FERR), serum HBsAg and HBV DNA quantitation were detected. The relation between HBsAg level and liver pathology were determined by spearman rank correlation analysis. The receiver operating characteristic curve was used to evaluate the accuracy of HBsAg level for liver inflammation and fibrosis.</p><p><b>RESULTS</b>The body mass index (BMI), age, gender, genotype and family history had no effective on liver inflammation and fibrosis (P < 0.05). With the progressing of inflammation and fibrosis, the serum AST and ALT raise obviously (chi2 = 71.193, 96.344, 47.847, 63.981; P = 0.000, 0.000, 0.000, 0.000). When fibrosis reached to S4, the level of HBV DNA decreased obviously (chi2 = 33. 322; P = 0.000). With the aggravation of inflammation and fibrosis, the serum HBsAg gradually descended (chi2 = 68.173,15.719; P = 0.000, 0.000). The areas under operating characteristics curves of HBsAg predicted < or = G3 and < or = S3 were 0.732 and 0.793, and the specificity were 0.778, 0.891, and sensitivity were 0.685, and 0.633, respectively.</p><p><b>CONCLUSION</b>The level of HBsAg of Chinese CHB patients descended gradually with the aggravation of liver inflammation and fibrosis. The serum HBsAg had a higher specificity to predict < or = G3 and < or = S3 of CHB patients. But there had superiority of predicting fibrosis than inflammation.</p>

Analysis of 11 cases of mycoplasma pneumoniae infection combined with Kawasaki disease / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To study the clinical characteristics of pediatric Kawasaki disease complicating mycoplasma pneumoniae pneumonia.</p><p><b>METHODS</b>Retrospective analysis was conducted on 11 children who had been diagnosed with Kawasaki disease with Mycoplasma pneumoniae pneumonia.</p><p><b>RESULTS</b>The 11 cases presented with varying degrees of fever, conjunctival congestion, skin rashes, lymphadenectasis, distal extremities lesions, heart and lung lesions. 8 of them were standartly treated with azithromycin, while 3 of them were treatad with azithromycin and erythromycin. 2 patients with pleural effusion complicated by lobar pneumonia consolidation were treated with gamma globulin combined aspirin. All of the 11 patients were healed.</p><p><b>CONCLUSION</b>Infections are common at the diagonosis of KD. Reasonable examination and antibiotics is useful to cure KD with MPP.</p>

Protective effects of rhein on hepatic progression in HBV-transgenic mice with nonalcoholic steatohepatitis induced by a high-fat diet / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the beneficial effects of Rhein (RH) on hepatic progression in hepatitis B virus (HBV)-transgenic mice with nonalcoholic steatohepatitis induced by a high-fat (HF) diet.</p><p><b>METHODS</b>A mice model of HBV chronic infection concomitant with liver steatosis was induced by a HF diet in 4-week old HBV-transgenic mice for 16 weeks (n = 130). Thereafter, the mice were divided randomly into control group (back to normal chow), model group (continuing HF diet), RH group [continuing HF diet and administering with 120 mg/(kg x d) RH by gavage] and Essentiale group [continuing HF diet and administering with 69.2 mg/(kg x d) Essentiale by gavage] with 30 mice in each, and were sacrificed at the end of 24-week and 48-week respectively. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG) and fasting plasma glucose (FPG) were measured by an automatic biochemical analyzer, and serum HBV-DNA was determined with qPCR. Hepatic histology was evaluated by HE staining with a light microscope.</p><p><b>RESULTS</b>(1) An histological change composed of steatosis, lymphocytes intralobular infiltration and ballooning was observed after 48 weeks feeding of HF diet, in part mimicking that of NASH patients as evidenced by a NAFLD activity score (NAS) of 3.58 +/- 1.44 points. (2) Histologically, the NAS of model group was higher than that of control group at both time points. RH failed to lessen NAS whereas Essentiale improved the NAS at 48-week. (3) Serum levels of TC, TG and FPG were significantly different between 4 groups at 24-week, with a comparable low value in both RH and Essentiale group. A similar change was evident at 48-week. (4) In terms of HBV viral load, a significantly lower level in Essentiale group than the others was observed at both time points.</p><p><b>CONCLUSION</b>HF diet feeding is able to induce a mouse model of HBV chronic infection concomitant with NASH. RH is effective in alleviating the glucose and lipid metabolism but ineffective in improving the hepatic histology in this model, in contrast, backing to normal chow achieved a better effect in this aspect.</p>

Expression of TGF-beta1/Smad protein in rat liver fibrosis model and the role of IFN-gamma / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To study the impact of IFN-gamma on liver fibrosis and its possible mechanism. Thirty healthy male SD rats were randomly divided into two groups: fibrosis model group, IFN-gamma treatment group. Experimental liver fibrosis was induced by subcutaneous injection of CCl4. After 12-week-treatment, serum hyalurnic acid and TGF-beta1 was examined, histopathological changes and degrees of fibrosis were observed by optical microscopy. Meanwhile, the expression of TGF-beta1, TbetaR- I and Smad2/3 proteins was detected by immunohistochemistry and quantified by using computerized image analysis.</p><p><b>RESULTS</b>(1) Pathological observation of hepatic specimens: histological examination showed that there were significant difference between normal group and fibrosis model group by comparing with the degrees of inflammation and fibrosis (P < 0.05). And the difference between fibrosis model group and IFN-gamma treatment group was significant (P < 0.05). (2) Changes of the hepatic fibrosis index (serum HA and TGF-beta1): the levels of serum HA, TGF-beta1 in fibrosis model group were higher than IFN-gamma treatment groups (P < 0.05). (3) Changes of gene protein levels about TGF-beta1/Smad: the expressions of TGF-beta1, TbetaR- I and Smad2/3 in rat hepatic tissue were detected with immunohistochemistry techniques. The expressions of the three items in model group were higher than normal group (P < 0.01). The difference between model group and IFN-gamma treatment group was significant (P < 0.05);</p><p><b>CONCLUSION</b>IFN-gamma treatment group had significant results on treating experimental hepatic fibrosis. By the way of inhibiting expressions of TGF-beta1, TbetaR- I, Smad2/3, IFN-gamma treatment group exerted its anti-fibrosis effect.</p>

Study on the correlation between chronic asymptomatic HBV carriers of yin asthenia constitution and genotypes of HLA-DRB1 and HLA DQA1 alleles / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study on the correlation between chronic asymptomatic HBV carriers (ASC) of yin asthenia constitution and genotypes of HLA-DRB1 and HLA DQA1 alleles.</p><p><b>METHODS</b>Totally 105 ASC were assigned to two groups according to their constitutions, i.e., the yin asthenia group (47 cases) and the non-yin asthenia group (58 cases). The genotypes of HLA-DRB1 and HLA DQA1 alleles were determined using PCR-SSP.</p><p><b>RESULTS</b>The gene frequency of HLA-DRB1 * 09 allele and HLA-DQA1 * 0301 allele (being 12.1% and 19.1%) were obviously lower in the yin asthenia group than in the non-yin asthenia group (being 27.8% and 39.7%, P < 0.05). The gene frequency of HLA-DRB1 * 11 allele and HLA-DQA1 * 0501 allele were obviously higher in the yin asthenia group (being 12.1% and 28.7%) than in the non-yin asthenia group (4.3% and 9.5%), showing statistical difference (P < 0.05, P < 0.01).</p><p><b>CONCLUSIONS</b>HLA-DRB1 * 09 allele and HLA-DQA1 * 0301 allele might be the molecular bases for non-yin asthenia patients with ASC. HLA-DRB1 * 11 allele and HLA-DQA1 * 0501 allele might be the molecular bases for yin asthenia patients with ASC.</p>

Impact of liver steatosis on antiviral effects of pegylated interferon-alpha in patients with chronic hepatitis B / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the impact of hepatic steatosis on virologic response in chronic hepatitis B (CHB) patients treated with pegylated interferon-alpha (PEG-IFNa).</p><p><b>METHODS</b>Ninety-six naive patients positive for hepatitis B e antigen (HBeAg) and with biopsy-proven CHB were administered PEG-IFNa-2a or PEG-IFNa-2b for 48 weeks. Virologic response (HBeAg clearance and hepatitis B virus (HBV) DNA less than 5 log10 copies/ml) and biochemical response (alanine transaminase (ALT) normalization) were compared between patients with (n=34) and without (n=62) steatosis.</p><p><b>RESULTS</b>The HBV DNA titer in the steatosis group was significantly lower than that of the non-steatosis group (6.961.27 vs. 7.541.28 log10 copies/ml; t=2.161, P=0.033). After 48 weeks of PEG-IFNa treatments, there was no significant difference in HBeAg seroconversion or the percentage of undetectable HBV DNA (less than 3 log10 copies/ml) between steatosis and non-steatosis patients. However, the steatosis patients presented with a significantly lower complete response rate (virologic response plus biochemical response) compared to non-steatosis patients (26.5% vs. 48.4%; x² =4.373, P=0.037). Of the 45 CHB patients with undetectable HBV DNA after 48 weeks of treatment, seven did not achieve ALT normalization. The rate of patients with non-biochemical response was significantly higher in the steatosis group than in the non-steatosis group (33.3% vs. 6.67%; P=0.032).</p><p><b>CONCLUSION</b>Hepatic steatosis does not affect the virologic response, but does affect the biochemical response in CHB patients treated with PEG-IFNa for 48 weeks.</p>

Value of delta model for end-stage liver disease in evaluating the prognosis of liver failure patients with hepatitis B virus / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To evaluate the prognostic value of the model for end-stage liver disease (MELD) and deltaMELD in liver failure patients infected with hepatitis B virus.</p><p><b>METHODS</b>Based on prospective study design, 98 hospitalized cases were studied and followed up for 24 weeks. The clinical data were recorded. We calculated the score of MELD and deltaMELD, and also compare the score between the survival group and death group. Using ROC curve plotting obtained the better decisive threshold. The case fatality rate were compared at different time points which the patients were classified by the best critical value of MELD and deltaMELD. We draw the Kaplan-Meier survival curve of different group and analyse the change of survival rate by log-rank analysis.</p><p><b>RESULTS</b>52 of 97 patients died and 46 survive during 24 weeks of followup. There was significant difference between the two groups for MELD and deltaMELD (P < 0.01). The case fatality rate in group which MELD > or = 23 was obviously higher than in that MELD < 23. The rate in group which deltaMELD > 4.5 was obviously higher than in that deltaMELD < 4.5 (P < 0.001). The area under curve (AUC) for the twelfth and 24th week's prognosis judgment of deltaMELD (0.823, 0.815) was larger than that of MELD (0.680, 0.684) (P < 0.05). Survival analyses (Kaplan-Meier) indicated that there were significant differences in cumulative survival rates among the groups which were grouped by optimization critical value ( P = 0. 000).</p><p><b>CONCLUSIONS</b>The scoring system of MELD also applied to the forecasting of prognosis for severe hepatitis B patients in China. The accuracy of deltaMELD to predict the prognosis was higher than that of MELD. The combination of MELD and deltaMELD showed good clinical practical value.</p>

Efficacy and safety of lamivudine plus adefovir combination therapy and entecavir monotherapy for chronic hepatitis B patients / 中华肝脏病杂志

To compare the efficacy and safety of Lamivudine (LAM) plus Adefovir dipivoxil (ADV) combination therapy and Entecavir (ETV) monotherapy for chronic hepatitis B patients. 120 patients with chronic hepatitis B managed in a single-centre clinical practice (median 96 weeks) were split into 2 cohorts, one was treated with de-novo combination Lamivudine (100 mg/day) plus Adefovir (10 mg/day) (LAM+ADV), the other with Entecavir (0.5 mg/day) monotherapy. Serum levels of ALT, creatinine, HBsAg, HBeAg and HBV viral load, together with genotypic resistence were analyzed at 0, 12, 24, 48, 96 weeks, respectively. HBV DNA was determined by real-time PCR. HBsAg and HBeAg were assessed by chemiluminescence. Serum levels of ALT and creatinine were detected by automatic biochemical analyzer. HBV genotypic resistence was tested by direct sequencing. (1) At the time point of 96 weeks, a total of 99 patients (51 cases in combination therapy cohort and 48 case in monotherapy cohort) were compared. The baseline characteristics as for HBV viral load, median age, serum levels of ALT and creatinine were compatible between combination therapy cohort and monotherapy cohort. (2) The rates of HBV DNA values is less than 300 copies/ml and HBV DNA values is less than 1000 copies/ml had no significant difference between LAM + ADV and ETV cohorts by the 12 and 24 weeks (P more than 0.05). (3) At the time point of 48 weeks, the rates of HBV DNA is less than 1000 copies/ml, HBeAg seroconversion, and ALT normalization were similar in both cohorts, though the rate of HBV DNA values is less than 300 copies/ml was obviously higher in combination therapy cohort than that of monotherapy cohort (90.7% vs 76%, P values is less than 0.05). (4) At the time point of 96 weeks, the rates of HBV DNA values is less than 300 copies/ml (96.1% vs 79.2%), HBV DNA values is less than 1000 copies/ml (98% vs 87.5%) and the HBeAg seroconversion (41.7% vs 16.7%) were markedly higher in combination therapy cohort than those of monotherapy cohort statistically (P values is less than 0.05 for all). The mean values of decreases for HBV viral loads and HBsAg levels were smilar in both cohorts at 48 and 96 weeks. (5) Elevated serum creatinine not be found in both cohorts at the end of treatment. (6) No virological breakthrough occurred in combination therapy cohort at the end of treatment. Four patients in monotherapy cohort were found with virological breakthrough at 96 weeks and three cases among were confirmed to be of variants associated with ETV resistance (rtL180M + T184L + M204V). Present study suggests that Lamivudine plus Adefovir dipivoxil de-novo combination therapy was more efficacious than Entecavir monotherapy for CHB patients and the tolerance is compatible.

P53 expression in liver tissue of patients with chronic hepatitis B and its influencing factors / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To observe p53 expression in liver tissue of patients with chronic hepatitis B and its influencing factors.</p><p><b>METHODS</b>17 cases HBeAg-negative chronic hepatitis B patients and 31 cases HBeAg-positive chronic hepatitis B patients were divided into 2 groups.</p><p><b>RESULTS</b>(1) HBeAg-negative chronic hepatitis B patients were older, mostly male and HBV DNA lower. These three indicators between two groups patients appeared statistical difference. Serum markers were no statistical difference between two groups patients except Glo. (2) Pathological inflammation and fibrosis Staging were no statistical difference between two groups patients. p53 expression positive rate and p53 expression semi-quantitative scoring in liver tissue were no statistical difference between the two groups. (3) Logistic regression analysis showed that only liver fibrosis staging (S) is a risk factor for p53 expression. Compared with the S0-1, p53 expression increased by 3.9 times the rate of positive in S > or = 2.</p><p><b>CONCLUSION</b>Liver fibrosis staging in patients with chronic hepatitis B is a risk factor for p53 positive expression in liver.</p>

The effect of extract of ginkgo biloba leaf during the formation of HBV-related hepatocellular carcinoma / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the effect of extract of ginkgo biloba leaf (EGb) during the formation of HBV-related hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>99 HBV transgenic mice were randomly divided into control group, high-dose group, low-dose group. High-dose group and low-dose group were intraperitoneal injected 35mg/(kg x d) and 17.5 mg/(kg x d) of the shuxuening injection. Control group without special treatment. The serological markers and immunohistochemical markers in liver tissue will be done at the first 12 months and 18 months.</p><p><b>RESULTS</b>(1) HBV transgenic mice can be found HCC at the 18 months. The incidence of HCC was lower in high-dose group and low-dose group, there was statistically different among the three groups. (2) The semi-quantitative scoring of liver HBx expression was highest in the control group at the 12 months. The semi-quantitative scoring of liver HBx, p53 and Bcl-2 expression was highest in the control group at the 18 months. They all appeared statistically different among the three groups. (3) Spearman correlation analysis showed that HCC incidence and liver tissue HBx, p53, Bcl-2 expression was a certain degree of positive correlation, r was 0.536, 0.487 and 0.403, P < 0.05.</p><p><b>CONCLUSION</b>EGb can reduced the incidence of the HCC with HBV transgenic mice. The reason may be that the EGb can reduce liver HBx, p53, Bcl-2 protein expression in the HBV transgenic mice.</p>

Analysis of drug-resistant multi-loci mutation of P area of HBV genome in 32 patients with chronic hepatitis B / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>In order to deeply understand the effects of nucleoside analogues to HBV DNA polymerase area, which initiate a state of drug resistance due to HBV genome mutation.</p><p><b>METHODS</b>Using PCR product direct sequencing method to test the gene sequence of P area of HBV genome of the patients who taking nucleoside analogues and showing signs of virologic breakthrough.</p><p><b>RESULTS</b>More resistance mutations can be find in HBV DNA polymerase area, which causing clinically cross drug resistance and multiple resistance.</p><p><b>CONCLUSION</b>We should choose higher genetic barrier for the initial treatment. And the patients long-term using of nucleoside analogues, should be regularly monitored serum HBV DNA level, in order for early detection of virological breakthrough and timely intervention.</p>

Analysis of 96 cases with novel H1N1 influenza A / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To review the epidemiologic and clinical characteristics of 96 cases with novel H1N1 influenza A, and improve the diagnosis and treatment level of novel H1N1 influenza A.</p><p><b>METHODS</b>96 cases of novel H1N1 influenza A admitted to the isolation wards from Oct 20 to Sep 23, 2009 were studied. Their epidemiologic, clinical, laboratory, and radiologic characteristics were analyzed.</p><p><b>RESULTS</b>The median age of the 96 patients was 26.52 +/- 10.62 years (range, 5 to 60 years). Sixty-four of the 96 patients had a close contact with novel H1N1 influenza A patients. The main symptoms included fever 100%, cough 86.4% , sore throat 66.6% and myalgia 32.3%.</p><p><b>CONCLUSION</b>The clinical presentation of novel H1N1 infection is largely indistinguishable from that of seasonal influenza. Combines both a symptom complex with the epidemiological investigation and laboratory characteristics can improve the accuracy of diagnosis of novel H1N1 influenza A.</p>

Association of chinese medicine constitution and human leukocyte antigen-DQA1 gene polymorphism with outcomes of hepatitis B virus infection / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the Chinese medicine constitution types and human leukocyte antigen (HLA)-DQA1 gene polymorphism in patients with hepatitis B (HB) virus infection in Chinese Han population of Zhejiang Province, for exploring the roles of constitution factor in pathogenesis of HB.</p><p><b>METHODS</b>A total of 240 subjects, including 120 biopsy-proven chronic HB (CHB), 60 HB asymptomatic carrier (ASC) and 60 resolved from HBV infection spontaneously (RHBS) were studied. Their Chinese medicine constitution type was judged by Wangqi's classification, and their genotype of HLA-DQA1 was detected by polymerase chain reaction sequence specific primer for comparing the difference between groups in distribution frequency (DF) of constitution types and genes.</p><p><b>RESULTS</b>(1) As compared with the RHBS group, DF of yin-deficiency constitution and phlegm-dampness constitution in the CHB group was significant higher (20.0% vs. 6.7% and 12.5% vs. 1.7%), and that of placid constitution was significant lower (11.7% vs. 31.7%), showing statistical significance between groups (OR = 3.5, 95% CI: 1.16-10.60; OR = 8.4, 95% CI: 1.09-65.42; OR = 0.161, 95% CI: 0.076-0.34; all P < 0.05). (2) As compared with the ASC group, DF of damp-heat constitution was significant higher (24.2% vs. 6.7%, P < 0.05, OR = 4.462, 95% CI: 1.49-13.36), and that of placid constitution was significant lower (11.7% vs. 45.0%, P < 0.01, OR = 0.285, 95% CI: 0.13-0.62) in the CHB group. (3) As compared with RHBS group, DF of HLA-DQA1 * 0201 allele in CHB group was significant higher (38.3% vs. 5.8%, P < 0.01, OR = 10.04, 95% CI: 4.48-22.48); and that of HLA-DQA1 * 0102 allele was significant lower (9.6% vs. 36.7%, P < 0.01, OR = 0.183, 95% CI: 0.10-0.32). (4) As compared with ASC group, DF of HLA-DQA1 * 0201 allele in CHB group was significant higher (38.3% vs. 7.5%, P < 0.01, OR = 7.667, 95% CI: 3.7-15.87), and that of HLA-DQA1 * 0102 allele was significant lower (20.0% vs. 9.6%, P < 0.01, OR = 0.424, 95% CI: 0.23-0.79).</p><p><b>CONCLUSION</b>Both Chinese medicine constitution and HLA-DQA1 gene polymorphism show connection with the outcomes of HB virus infection in Chinese Han population, but the real association between them is required for further study.</p>

Prognostic analysis of 336 patients with chronic severe hepatitis B / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the risk factors related to outcome of chronic severe hepatitis B.</p><p><b>METHODS</b>A total of 336 consecutive patients with chronic severe hepatitis B (CSHB) were analysed retrospectively. According to the outcome, objects were divided into survival group (n = 137) and death group(n = 199), then to observe the differences between them in respect to age, sex, family history, prothrombin activity (PTA), complications including ascites, infection, electrolyte disturbance, upper gastrointestinal bleeding, hepatic encephalopathy, hepatorenal syndrome and the corresponding quantity of complications in each individual, antivirus therapy, artificial liver support system (ALSS) therapy, and alprostadil therapy. Finally, risk factors related to prognosis were selected by stepwise Logistic regression analyse.</p><p><b>RESULTS</b>In univariate analyse, significant differences between the two groups were found related to age, PTA, complications and its quantity (P < 0.01 for all), and antivirus therapy (P < 0.05) rather than sex, family history and treatment of ALSS or alprostadil. Logistic regression revealed that risk factors comprised of PTA and quantity of complications, antivirus therapy was the only protective factor.</p><p><b>CONCLUSION</b>A numbers of factors including age, PTA, complications and its quantity, and antivirus therapy affect the prognosis of CSHB, among which, antivirus therapy can reduce the death rate.</p>

Association between HLA-DQA1 gene polymorphism and the outcomes of hepatitis B virus infection / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the association between HLA-DQA1 gene polymorphism and the outcomes of hepatitis B virus infection in Chinese Han population.</p><p><b>METHODS</b>A total of 180 consecutive patients with biopsy-proven hepatitis B virus infection (120 patients with chronic hepatitis B and 60 patients with asymptomatic HBV carrier) and 60 subjects who resolved from HBV infection spontaneously were studied. Genotype of human leukocyte antigen(HLA)-DQA1 was detected by polymerase chain reaction sequence specific primer(PCR-SSP).</p><p><b>RESULTS</b>(1) The frequency of HLA-DQA1 * 0201 allele in chronic hepatitis B group was significant higher than the frequency in resolved from HBV infection spontaneously group (38.3% vs. 5.8%, P < 0.001, A = 10.04, 95% CI: 4.48-22.48). The frequency of HLA-DQA1 * 0102 allele in chronic hepatitis B group was significant lower than the frequency in resolved from HBV infection spontaneously group (9.6% vs. 36.7%, P < 0.001, A = 0.183, 95% CI: 0.10-0.32). (2) The frequency of HLA-DQA1 * 0201 allele in chronic hepatitis B group was significant higher than the frequency in asymptomatic HBV carrier group (38.3% vs. 7.5%, P < 0.01, A = 7.667, 95% CI:3.7-15.87). The frequency of HLA-DQA1 * 0102 allele in chronic hepatitis B group was significant lower than the frequency in asymptomatic HBV carrier group (20% vs. 9.6%, P < 0.01, A = 0.424, 95% CI: 0.23-0.79).</p><p><b>CONCLUSION</b>HLA-DQA1 gene polymorphism may play an important role in the outcomes of hepatitis B virus infection in-Chinese Han population. The HLA-DQA1 * 0102 allele could keep individuals away from HBV infection, and HLA-DQA1 * 0201 allele could aggravate persistant infection of HBV and hepatic inflammatory.</p>

Level of serum and liver tissue TGF-beta1 in patients with liver fibrosis due to chronic hepatitis B / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To detect the level of serum and liver tissue TGF-beta1 in patients with chronic hepatitis B, to study their relation to liver fibrosis and gain the evidence for diagnosis of liver fibrosis.</p><p><b>METHODS</b>The liver fibrosis grades (S0-S4) of 131 cases with chronic HBV infection were diagnosed after liver biopsy. Serum TGF-beta1 was detected by enzyme-linked immunosorbent assay, and the semiquantitative analysis was applied after detecting the expression of TGF-beta1 in liver tissue with immunohistochemistry. Their relations to liver fibrosis were analyzed.</p><p><b>RESULTS</b>Serum and tissue level of TGF-beta1 increased significantly with the development of fibrosis, and the same result was obtained between themselves (P < 0.01). There was very significant difference for serum level of TGF-beta1 among the groups with different fibrosis grades (P < 0.01). Serum levels of TGF-beta1 were decreased significantly comparing the Group S0 or S1 to S4 (P < 0.005). There were significant difference for serum level of TGF-beta1 among S0 and the others (P < 0.005). And there was significant difference between S1 and S3 (P < 0.005). The expression level of TGF-beta1 in liver tissue has no significant difference between group S3 and S4 (P > 0.05). However, the differences were significantly among the other comparisons (P < 0.01).</p><p><b>CONCLUSION</b>There is close relation between the level of TGF-beta1 and the different liver fibrosis grades due to chronic hepatitis B. The serum level of TGF-beta1 is a potential noninvasive maker for diagnosis of liver fibrosis.</p>