Objective To investigate the association between the polymorphism at position 627 in IL-10 promoter and the prevalence of HBV related cirrhosis. Methods PCR-restriction fragment length polymorphism (PCR-PFLP) was performed to detect polymorphisms of IL-10 promoter-627 in 220 patients with HBV related cirrhosis and 200 healthy controls. The contribution of polymorphism at position 627 to HBV related cirrhosis was calculated. Results The frequency of AA and CA genotypes and A allele at position 627 of IL-10 promoter region were significantly higher in patients with HBV-related cirrhosis than that of healthy controls (X2 = 7.46,5.72,13.78, P < 0.01 or P < 0.05 ). Conclusion There are significant association between the polymorphism at position 627 in the IL-10 promoter region and the prevalence of HBV related cirrhosis.

Objective To construct DNA vaccine expressing HIV-1 AE2f gp145-tat-rev-nef fusion gene( AE-Gp145TRN) and to compare the immunogenicities of DNA vaccines expressing Tat, Rev and Nef in gene fusion formulations of tat-rev-integrase(c-half)-vif-nef( AE-TRIVN) and AE-Gpl45TRN. Methods DNA vaccine was constructed by inserting the codon optimized HIV-1 AE2( gp145-tat-rev-nef fusion gene into mammalian expression DNA vector. In vitro expression efficiency of the constructed DNA vaccine was determined by Western blot and the immunogenicities of AE-Gpl45TRN and AE-TRIVN were compared by immunizing female BALB/c mice. IFN-r ELISPOT assay was used to read out the specific T cell immunity. Results Western blot assay showed the constructed DNA vaccine could be expressed efficiently in vitro. After vaccination, AE-TRIVN mounted significantly higher T cell responses against Tat, Rev and Nef[(148±91)SFCs/106 splenocytes]than Gpl45TRN[(55±28) SFCs/106 splenocytes]. Specific T cell responses elicited by AE-TRIVN predominantly targeting Rev, whereas Gpl45TRN could significantly enhance T cell responses against Nef. Conclusion AE-TRIVN and Gpl45TRN induced distinct T cell response modalities, which implied different gene fusion formulations may affect the immunogenicity of specific DNA vaccines.

Chronic hepatitis B (CHB) is still a global public health problem, resulting in the high risk of decompensated cirrhosis and hepatocellular carcinoma.At present, there are no single available medications that can induce both potent HBV DNA suppression, and high rates of HBeAg and HBsAg clearance.Therefore, there is great interest in developing combination therapies for patients with chronic HBV infection, which can achieve sustained viral suppression and HBsAg negative inversion after a finite course of treatment leading to clinical cure.This article reviews the current status and advances of combination therapy for CHB.

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Objective To compare the pre-existing mutations in reverse transcription region of HBV in patients with different HBV infection stages.Methods Totally 474 patients with chronic HBV infections,including 205 with chronic hepatitis B (CHB),153 with liver cirrhosis and 116 with hepatocellular carcinoma (HCC),were enrolled from the People' s Hospital of Shangyu and the First Affiliated Hospital of Zhejiang University during January 2011 and June 2013.All patients had not received nucleos (t)ide analogues treatment.HBV RT region mutations and genotypes were determined by PCR followed by sequencing.SPSS14.0 was used for statistical analysis.Results There were 387 (81.6％) patients with HBV genotype B,in which 156 were with CHB,124 were with liver cirrhosis,and 107 were with HCC.Nucleos(t)ide analogues-related mutations were observed in all the above 387 patients.rtS106C mutation was more popular in CHB and liver cirrhosis (14.1％ and 14.5％) patients than that in patients with HCC (4.7％) (x2 =6.126,6.207,P ＜0.05); And the positive rates of rtD134E/G/N/S mutations were also higher in CHB and cirrhotic patients (21.8％ and 20.2％) than that in HCC patients (10.3％,x2 =5.933,4.263,P ＜ 0.05).rtD134E/G/N/S and rtS106C mutations were correlated with HBeAg (P ＜0.01) and gender (P ＜ 0.05),but not with HBV virus load and age (P ＞ 0.05).The mutation frequencies in A-B interdomain were higher in CHB and cirrhotic patients (5.3％ and 5.6％) than that in HCC patients (3.5％,x2 =9.018,11.018,P ＜ 0.01).Conclusions Nucleos (t) ide analogues-related mutations exist in various HBV infection stages.rtSl06C and rtD134E/G/N/S mutations may be involved in necro-inflammation,and A-B interdomain mutations may be correlated with necro-inflammation,immune response and fibrosis in chronic liver diseases.

Objective To compare the 2-year efficacy of de novo combination therapy with lamivudine (LAM) and adefovir dipivoxil (ADV) to that of entecavir (ETV) monotherapy in treatment of patients with hepatitis B virus ( HBV )-related decompensated cirrhosis.Methods A total of 120 naive patients with HBV-related decompensated cirrhosis admitted to Shangyu People's Hospital and the First Affiliated Hospital of Zhejiang University from January 2007 to April 2008 were enrolled,in which 60 were treated with LAM and ADV combination therapy,and other 60 patients were treated with ETV monotherapy.Tests for liver and kidney function,alpha-fetoprotein,HBV serum markers,HBV DNA load,prothrombin time (PT),and ultrasonography or CT scan of liver were performed every 1-3 months.Repeated measure ANOVA and x2test were used to compare the efficacy,side effects and accumulated survival rates at 12 and 24 month in two groups.Results Forty-five patients in each group were followed-up for 24 months.There was no significant difference in HBV DNA negative rates and ALT normalization rates at month 12 (x2 =2.12 and 2.88,P ＞0.05 ) and month 24 between two groups (x2 =3.21 and 3.24,P ＞ 0.05); while HBeAg seroconversion rate in LAM + ADV group at month 24 was significantly higher than that in ETV group (43.5％ vs.36.4％,x2 =4.09,P＜0.05).Viral breakthrough occurred in 2 cases (4.4％) by month 12 and 3 cases (6.7％) by month 24 in LAM + ADV group,and no viral mutation was observed; while in ETV group,viral breakthrough occurred in 1 case ( 2.2％ ) by month 12 and 2 cases (4.4％) by month 24,and viral mutation was observed in 1 case (2.2％) by month 24.At the end of month 24,increase of AIb (F=18.9 and 17.3,P＜0.05),decrease of TBil and ALT (F=16.5,17.1 and 23.7,24.8,P ＜0.05 ),shortening of PT ( F =22.7 and 24.5,P ＜ 0.05 ),and the improvements of CTP and MELD scores (F=18.5,17.8 and 24.2,23.8,P＜0.05) were observed in both groups.The accumulative rates of mortality or liver transplantation were 16.7％ ( 10/60 ) and 18.3％ ( 11/60 ) in LAM + ADV and ETV groups,respectively.No blood creatinine increased above the normal upper limit was observed in both groups.Conclusion Both LAM + ADV combination therapy and ETV monotherapy can effectively inhibit HBV replication,improve liver function,decrease mortality and viral resistance,but the 24-month HBeAg seroconversion rate in combination therapy group is higher than that in monotherapy group.

Objective To analyze CD127 expression on the memory CD8+ lymphocytes from hepatitis B e antigen (HBeAg) positive chronic hepatitis B (CHB) patients treated with peginterferon α-2a (Pegasys). Methods Thirty HBeAg positive CHB patients were treated with peginterferon α-2a 180 μg once a week for 48 weeks and followed up for 24 weeks. The memory CD8+ lymphocytes were characterized by expressing CD45RA and CD27 markers. CD127 expression on cell surface was measured by four-colour flow cytometry. The difference of mean values between groups was evaluated by Mann-Whitney test. Results The CD127 expression on CD8+ T lymphocytes was significantly lower in HBeAg positive CHB patients compared to healthy controls (Z=2.889, P＜0.05), which was negatively correlated with serum hepatitis B virus (HBV) DNA level and HBeAg titers. The CD127 expression increased along with the decrease of HBV DNA and HBeAg after 24-week, 48-week and 72-week treatment in patients showing good response to peginterferon α-2a, while CD127 expression didn't change markedly in non responders (Z24w = 1.954, Z48w = 2.789, Z72w = 2. 989; all P＜0. 05). Conclusion CD127 expression on memory CD8+ lymphocytes increases along with effective anti-HBV treatment in CHB patients, which can be used as a marker for evaluating the effectiveness of anti-viral treatment.

Objective: To analyze the basic thyroid hormone level on long term prognosis and peri-operative recovery in patients after heart transplantation (HT) at the terminal stage of heart failure (HF).
Methods: A total of 270 consecutive patients who received HT at the terminal stage of HF in our hospital from 2009-09 to 2014-07 were retrospectively studied. According to serum levels of thyroid stimulating hormone (TSH), the patients were divided into 3 groups: TSH < 0.55 mIU/L group, TSH (0.55-2.5) mIU/L group and TSH > 2.5 mIU/L group. The peri-operative recovery condition and long term prognosis were observed and compared among 3 groups.
Result: The average age of patients was at (44.58 ± 13.30) years including 228 (84.4%) male and 42 (15.6%) female. The average post-operative follow-up period was (31.88 ± 17.48) months with 100% follow-up rate. There were 41.8% of patients with hypothyroidism, and 46 (17.0%) patients with low T3 syndrome, 56 (20.7%) with subclinical hypothyroidism and 11 (4.1%) with clinical hypothyroidism. The ratio of low level thyroid hormone in HT patients was much higher than general population. For peri-operative recovery, the ICU stay time and mechanical ventilation time were similar among 3 groups,P>0.05, while TSH (0.55-2.50) mIU/L group had the shortest times and TSH > 2.50 mIU/L group had longest times. For long term prognosis, no matter uni-/multi- aviate regression analysis or Kaplan-Meier surviving curve all suggested that TSH > 2.50 mIU/L was the independent risk factor inlfuencing the prognosis of HT patients at the terminal stage of HF. Upon TSH increasing, the patients would have worse prognosis accordingly.
Conclusion: Serum level of TSH > 2.50 mIU/L was the independent risk factor in HT patients at the terminal stage of HF.

Objective To compare the efficacy of add-on adefovir dipivoxil (ADV) therapy and switch-to entecavir (ETV) monotherapy in chronic hepatitis B (CHB) patients with suboptimal response to lamivudine (LAM).Methods A prospective study was performed in 120 CHB patients from Zhuji People' s Hospital and the First Affiliated Hospital of Zhejiang University School of Medicine during June 2010 and June 2011.All patients previously received more than 24 weeks LAM treatment,but HBV DNA was still positive.Patients were randomized assigned to two groups:60 patients received add-on ADV therapy and another 60 switched to ETV monotherapy.Both groups were treated for 48 weeks.Liver and kidney function,alpha-fetal protein (AFP),HBV serum markers,HBV DNA and prothrombin time (PT) were examined,and ultrasonography or CT scan of liver was performed every 1-3 months.x2 test was used to compare the HBV DNA negative rates,HBeAg seroconversion rates,resistance rates and adverse reaction at week 48 between two groups.Results Thirty-three out of 38 patients (86.8％) with baseline HBV DNA 103-105 copies/mL became HBV DNA negative after add-on ADV treatment for 48 weeks,twenty-seven out of 39 patients (69.2％) with baseline HBV DNA 103-105 copies/ml became HBV DNA negative after switch-to ETV treatment.There was a statistical difference between two groups (x2 =4.578,P ＜ 0.05).Sixteen out of 22 patients (72.7％) with baseline HBV DNA ＞ 105 copies/mL became HBV DNA negative after add-on ADV treatment for 48 weeks,while only 52.4％ (11/21) patients achieved HBV DNA negative in the switch-to ETV group.There was also a statistical difference between two groups (x2 =4.865,P ＜0.05).None of patients in add-on group developed virological breakthrough and resistance,while 5 patients in switch-to ETV group developed virogical breakthrough and 3 patients developed genetic mutation.Among them,rtM204V + rtL180M + rtS202G mutation was detected in 2 patients,and rtM204V + rtL180M +rtT184A mutation was detected in 1 patient; all mutations happened in the baseline HBV DNA ＞ 105 copies/mL group.Conclusion The add-on ADV therapy is better in viral inhibition than switch-to ETV therapy for CHB patients with suboptimal response to LAM,and it can reduce the occurrence of drug resistance.

0 05) Left ventricular (LV) end diastolic pressure (LVEDP), volume (LVV), weight (LVW) and septal thickness (STh) were all higher and left ventricular pressure maximal rate of rise and fall (?d p /d t ) were lower (all P