Objective To investigate the impact of cytotoxic T lymphocyte（CTL） epitope mutation of HBV envelope and core protein on disease progress in patients with hepatitis B. Methods 38 individuals with asymptomatic HBsAg carrier,35 patients with chronic hepatitis B and 23 with liver cirrhosis were recruited in this study. Gene sequencing analysis of HBV core region and envelope region was carried out in all enrolled patients to unveil any possible CTL epitope mutation. Results The mutation rates of locus 41~49,88~96,97~108,172~180 and 185~194 of CTL epitope in HBV envelope region were 48（55.2%）,13（14.9%）,11（12.6%）,9（10.3%） and 6（6.9%）,respectively;60% of mutation at locus 41~49 in patients with chronic hepatitis B and 65.2% in with liver cirrhosis were significantly higher than 31.6% in asymptomatic HBsAg carriers（P<0.05）;the mutation rates at 18~27 and 91~95 locus of CTL epitope in HBV core region were 56.2% and 43.8%,respectively;the mutation rates at locus 18~27 were also higher in patients with CHB（20.0%） and LC（30.4%） than that in asymptomatic HBsAg carriers （10.5%,P<0.05）;Multivariate analysis showed that locus 41~49 mutation was an independent risk factor for the progress of CHB to LC. Conclusion CTL epitope mutation of HBV is a significant cause for the chronicity of hepatitis B virus infection.

Objective To evaluate the efficacy of Compound Biejia Ruangan Tablets（RGP） on preventing the progression of liver fibrosis in patients with chronic hepatitis B（CHB）. Methods 304 patients with CHB were divided into treatment group（n=219），and control group （n=85）. The patients in treatment group were given RGP orally at dose of 4 tablets，3 times daily，and in control group given Anluo Huaxian pills （ALHX） orally，at dose of 6 g，2 times daily. The serum hyaluronan，laminin，collagen type Ⅳ，and PCⅢ levels were detected by ELISA. Results At the end of 24-week treatment，the significant improvement of Chinese medicine symptom as assessed by curative effect full analysis set（FAS） in treatment group was 72.9%，higher than 56.8%（P=0.004） in control group；the total efficiency in treatment group was 89.3%，higher than 80.7% in control group（P=0.029）；The curative effect analysis of four items for liver fibrosis showed that the significant efficiency in treatment group was 35.3%，better than 22.2% in control group（P=0.016）；the total effective rate was no statistically significantly different between the two groups；For serum liver fibrosis indexes，the hyaluronic acid in treatment group fell by（87.4±111.2） ng/mL，better than that in control group，which fell（61.2±66.2） ng/mL after treatment （P=0.01）；The changes of serum laminin，typeⅣcollagen and pro-collagen Ⅲ in the two groups had no statistical differences（P>0.05）；The normalization rates of liver function indexes after treatment had no statistically significant difference between the two groups（P>0.05）；In terms of safety，we found no adverse reaction in the two groups. Conclusion It is safe and effective to treat patients with CHB by RGP，which will improve the symptoms，and decrease serum liver fibrosis indexes.

ObjectiveTo observe the antiviral efficacy and safety of adefovir in the treatment of elderly patients with hepatitis B. MethodsFifty elderly patients aged over 65 year old with chronic hepatitis B （CHB） were divided into group A（n=30）and group B（n=20）,and thirty patients with hepatitis B aged （46.31±2.18） yr were selected in group C who took adefovir at dose of 10 mg daily as initial treatment as the same treatment as in group A. The three groups were observed at admission,12 weeks,24 weeks,48 weeks,96 weeks and 144 weeks after treatment for virologic response and renal functions. All patients were followed-up for three years. Results At 24 weeks,there was no significant difference of liver normalization rates in group A （83.6%） and group C（86.7%）;At 48 weeks and 96 weeks,serum HBV DNA loss rate in group A was obviously higher than that in group C（80.0% and 80.0% vs. 60.0% and 66.7%,respectively,P<0.05）;At the end of three years,there was no statistically significant difference of blood creatinine in the three groups;At 96 week treatment,2 patients in group A had blood creatinine levels mildly elevated,but returning to normal after 2 month observation,3 cases in group C had mild abnormal creatinine elevation,not recovered within three months,but got back to normal when the dosage of adefovir half-decreased. Conclusion The application of adefovir in elderly patients with chronic hepatitis B can improve liver functions,and have a good antiviral efficacy.

Objective To explore the liver pathologic changes in chronic Hepatitis B （CHB） patients with mildly elevated serum alanine aminotransferase levels after two-year followed-up. Methods 167 CHB patients with serum ALT<2 upper limit of normal（ULN） who underwent liver biopsy were included in this study. The patients were followed-up for two years,and the liver biopsies were performed at presentation and at the end of two year observation. Serum HBsAg,HBeAg,HBV DNA and ALT were conventionally detected,and Logistic regression was conducted to find the influencing factors for the liver tissue pathology changes. Results 33（37.5%） had,and 55（62.5%） had not aggravated liver tissue injuries out of 88 hepatitis B virus carriers at the end of two year follow-up,the ages of those with aggravated liver injuries at presentation were（39.7±7.6） yr,older than in without liver injuries[（30.2±9.7）yr,P<0.05],and the serum HBeAg positive rate（51.5%） and the serum level of HBsAg [（3.22±0.51） lgIU/ml] were much lower than in those without liver injuries [（81.8%） and （3.50±0.53） lgIU/ml,respectively,P<0.05];The age was an important factor affecting liver pathological progress by Logistic regression analysis（OR=1.118,P=0.002）. 62（78.5%） had improved hepatic histological activity of Knodell 's score in 79 patients with CHB after antiviral therapy at the end of two year follow-up. Conclusion The risk of liver tissue pathological progression increased as the hepatitis B virus carriers get older than 40 years in those with serum HBeAg negative and mildly elevated serum ALT levels,and we recommends them having liver biopsy in time,and have antiviral therapy as necessary.

ObjectiveTo investigate the changes of HLA-DR mRNA,and Th17 and CD4⁺CD25⁺Treg cells in peripheral blood mononuclear cells（PBMCs） in patients with liver failure. Methods HLA-DR mRNA was detected by PCR,and Th17 and CD4⁺CD25⁺Treg cells were measured by flow cytometry in 50 patients with liver failure,including 15 arisen from hepatitis B,12 from drug-induced liver injury（DILI）,13 from alcoholic liver diseases,and 10 from autoimmune liver diseases,and in 17 patients with chronic hepatitis B and 10 healthy persons. Results The HLA-DR mRNA levels in PBMCs in patients with hepatitis B-induced liver failure was（134.5±15.2）,much higher than （17.9±1.2）in DILI-,（19.6±2.0）in alcoholic and[（11.2±1.2）,P<0.05] in autoimmune liver disease-induced liver failure;the percentages of Th17 cells and CD4⁺CD25⁺Treg cells [（4.4±0.6）% and（3.9±0.6）% or less,respectively] in patients with different etiologic liver failures were not significantly different（P>0.05）,while there were a significant difference as compared to（3.7±0.2）% and（6.1±0.4）% in patients with chronic hepatitis B or（2.1±0.7）% and（7.0±0.9）% in normal control （P<0.05）;the percentages of CD4⁺CD25⁺Treg cells in 19 died patients decreased gradually,while it increased gradually in 31 survived patients. Conclusion The HLA-DR mRNA levels and CD4⁺CD25⁺Treg cells are closely related to the illness severity of patients with liver failure,and they may be used as parameters to estimate the clinical prognosis.

ObjectiveTo investigate the efficacy of entecavir in treatment of patients with HBV-associated acute-on-chronic liver failure（HBV-ACLF）. Methods 74 patients with HBV-ACLF were enrolled in Third People’s Hospital,Nantong,from 2003 to 2012. Among them,37 patients were given entecavir while receiving liver-protecting treatment,and the other 37 cases were given only basic protecting treatment without any antiviral medication as control group. The clinical characteristic at administration,the results of liver function such as alanine transaminase （ALT）,aspartate transaminase（AST）,albumin （ALB）,creatine（Cr）,prothrombin time （PT） , the score of model for end-stage liver disease （MELD）,cumulative survival rates and recurrence rates within 24 months were compared between the two groups by means of t-test and Chi-Square test. ResultsThe serum levels of ALT,AST,ALB,Cr,plasma prothrombin activity（PTA） and MELD scores between the two groups had no statistical differences after 4-week,8-week and 12 week treatment;The morbidity of ascites,gastrointestinal bleeding,encephalopathy,and hepatorenal syndrome between the two groups had no statistical differences except the morbidity of ascites in the survivors of the entecavir group was 41.4%,lowwer than 66.7%（P<0.05） in the control group at the end of the fourth week;The survival rates in 37 patients receiving antiviral therapy at 8w,12w and 24w,were 75.7%,75.7% and 70.3%,much higher than 67.6%,56.8% and 54.1%（P<0.05）in the control;At the end of 2-year observation, there was no recurrence in 26 survivals with entecavir treatment, while the recurrence rate was 65.0%（P<0.001） in 20 patients without antiviral therapy in the control. ConclusionEnticavir treatment may improve the survival of patients with HBV-ACLF with less disease recurrence.

Objective This study is aimed at establishment of emodin-induced drug-induced liver injury in rats. Methods According to dose of emodin daily intake，100 male Wistar rats were randomly divided into five groups，e.g. high-dose group （16mg.kg^-1?d^-1），a larger dose （8 mg?kg^-1?d^-1），the middle dose group （4mg?kg^-1?d^-1），low-dose group （2 mg?kg^-1?d^-1） and the normal control group （fed an equal volume of distilled water），and each group had 20 rats. 5 rats were killed in each group at the end of 4th and 8th week. Other rats were all killed in the end of 12th week. The body weight of rats was measured. With HE and VG staining，the pathology of liver tissues were observed under microscope. The degree of fibrosis in liver tissues were compared by Radit analysis. Results Rats lived good in each group，and there were no deaths in each group or ascites formation;The body weight in high dose group were significantly lighter，and the body weight in normal group，low dose group，and middle dose group at 12th week were（335±10.56） g，（350.4±7.23） g and（338.6±7.54） g，respectively，much heavier than in high dose group[（300.4±8.91）g，P<0.01]；The inflammation activity and degree of hepatic fibrosis in liver tissues were both significantly more obvious in high dose group at 12th week（x²=14.75，P<0.05）. Conclusion The liver injury model in rats could be induced by emodin perfusion，which needs to be explored further in the future.

Objective To investigate MR diffusion-weighted imaging（DWI） in the diagnosis of hepatic fibrosis in rabbits. Methods Rabbits with CCl₄-induced liver fibrosis was established. 7 or 8 rabbits in model group and 2 or 3 rabbits in control group were sacrificed at each attempt,and a total of 30 rabbits in model and 10 rabbits in control group had DWI checked-up. Apparent diffusion coefficient（ADC） values of liver with different b values （b=300,500 and 1000 s/mm²,respectively） were calculated. The rabbits were sacrificed 12h after DWI scanning and the liver tissues were examined pathologically. Spearman correlation analysis was conducted to reveal the correlation between ADC values and fibrosis staging,and receiver operating characteristic （ROC） curve was used to assess the performance of ADC values in predicting the presence of ≥2 stage and ≥3 stage of hepatic fibrosis. Results There was a negative correlation between hepatic ADC values and fibrosis stage,and the optimal correlation was obtained with a b value of 500 s/mm²（r=-0.697,P=0.000）;There was a significant difference in hepatic ADC values between rabbits with ≤1 stage and ≥2 stage of fibrosis,as well as between ≤2 stage and ≥3 stage of fibrosis（P<0.05 for both） no matter at b=300,500 and 1000 s/mm²;When b value=500 s/mm²,the areas under the receiver operating characteristic curves（AUC） in discriminating ≥2 stage of fibrosis by ADC values were 0.912,given ADC value=1.58×10^-3mm²/s as cut-off value,and the sensitivity and the specificity were 90.2% and 75.0%,respectively;while in discriminating ≥3 stage of fibrosis,the AUC were 0.920 with ADC of 1.43×10^-3mm²/s as cut-off value,and the sensitivity and the specificity were 93.0% and 80.0%,respectively. Conclusion The hepatic ADC values can be employed tentatively in determining fibrosis staging and is expected to be a new approach for the diagnosis of hepatic fibrosis.

Objective To explore the therapeutic efficacy of entecavir combined with Fuzhenghuayu capsules in the treatment of patients with hepatitis B cirrhosis. Methods 60 patients with active hepatitis B related cirrhosis were randomly divided into observation group（n=30） and control group（n=30）. At the base of conventional therapy，patients in control group was given only entecavir，while in observation group was given entecavir combined with Fuzhenghuayu capsules，and both for 24 weeks. Serum indicators of hepatic fibrosis and liver function were recorded and analyzed. Results Serum hyaluronic acid （HA），laminin （LN），procollagen type III （PCⅢ，collagen-Ⅳ（Ⅳ-C），alanine aminotransferase （ALT），albumin （ALB），total bilirubin（TBIL），portal vein’s diameter，spleen length and spleen thickness in observation group and control group before the treatment had no significant differences [HA（334.7±119.8） ng/ml vs. （320.4±196） ng/ml；LN （183.2±79.6） ng/ml vs. （180.9±80） ng/ml；PC Ⅲ（252.5±139.8） ng/ml vs. （261.2±132） ng/ml；IV-C （203.3±74.1） ng/ml vs. （204.1±78.1） ng/ml；ALT （171.53±11.21） U/L vs. （169.87±13.32） U/L；ALB （33.46±7.53） g/L vs. （34.05±6.94） g/L；TBIL（49.33±10.1） μmol/L vs.（48.89±11.03） μmol/L；portal vein’s diameter （13.1±0.7） mm vs. （12.9±1.1） mm；spleen’s length （122.1±3.9） mm vs. （123.4±2.5） mm；spleen’s thickness （48.9±4.2） mm vs. （48.6±4.7） mm；P>0.05 for all]；After the treatment，the above-mentioned indicators in the two groups were statistically different [HA （158.2±79.1） ng/ml vs. （205.2±49.6） ng/ml；LN （104.3±59.7） ng/ml vs. （149.8±64.3） ng/ml；PC Ⅲ （140.2±76.4） ng/ml vs. （192.7±99.8） ng/ml；IV-C （111.4±56.8） ng/ml vs.（159.2±42.5） ng/ml；ALT（24.37±7.33） U/L vs. （54.89±6.65） U/L；ALB （41.02±6.3） g/L vs. （35.59±7.2） g/L；TBIL （10.32±8.03） μmol/L vs. （20.89±9.65） μmol/L；portal vein’s diameter （10.2±0.5） mm vs. （11.7±0.85） mm；spleen length （109.4±3.1） mm vs. （117.3±2.9） mm；spleen thickness（44.4±2.0） mm vs. （46.8±3.6） mm；P<0.05 for all]；The rate of serum HBV DNA loss in observation group after 24-week treatment was 83.3%，significantly higher than 40.0% in control group（P<0.05）. Conclusions The combination of entecavir and Fuzhenghuayu capsules exerts better therapeutic efficacy in the treatment of patients with liver cirrhosis.

Objective To investigate the correlation of serum ferritin （SF） and liver injuries in patients with chronic hepatitis B and liver cirrhosis after hepatitis B viral infection. Methods SF were detected in 38 patients with chronic hepatitis B,37 with hepatitis B-related liver cirrhosis and in 30 healthy persons,and the relationship between SF and ALT,AST,ALB of liver function,CEA,AFP,Ca125 of tumor markers was analyzed by Spearman rank correlation. Results SF levels in patients with chronic hepatitis B and with liver cirrhosis were（216.79±24.46） μg/l and（220.47±39.38） μg/l,respectively,much higher than in healthy control group[（71.23±4.69） μg/l,P<0.05];There was a significant positive correlation between SF and ALT,AST,GGT,ALP,TBIL,AFP,CA199 and CA50 in patients with chronic hepatitis B,while there was a significant positive correlation between SF and AST,LDH,AFP,CA199,CA724 and CA50 in patients with liver cirrhosis. ConclusionsThere is a significant correlation between SF and AST,AFP and Ca199 in patients with chronic hepatitis B viral infection-related liver disease. SF may be considered as an important reference index in the diagnosis of liver injury. The overload of iron may enhance the hepatic injury. Detection of SF level is useful in diagnosis,prognosis and treatment in patients with liver diseases.

Objective To observe the efficacy of patients with decompensated hepatitis B cirrhosis after splenectomy or partial splenic artery embolization. Methods 108 patients with decompensated hepatitis B-related liver cirrhosis were recruited in this study,and 50 received splenectomy,28 received partial splenic artery embolization and 30 received conventional medical therapy as control. Results At the end of one-year follow-up,the peripheral white blood cell and platelet counts in control group were（3.3±0.6）×10⁹/L and（56.3±5.8）×10⁹/L,significantly lower than in spleen resection group（6.2±0.6）×10⁹/L and（126.5±12.7）×10⁹/L（P<0.05）,or in partial splenic artery embolization group（7.2±0.8）×10⁹/L and （112.8±10.6）×10⁹/L（P<0.05）;the peripheral blood CD₄,CD₄/CD₈ ratio and albumin levels were（32.5±3.5）%,（1.1±0.2）and （24.9±3.8） g/L,significantly lower than in patients with splenectomy（41.8±4.2） %,（1.9±0.2） and （29.1±3.7） g/L（P<0.05）,or in with partial splenic artery embolization（41.6±4.9） %,（1.7±0.2） and（28.2±4.0） g/L（P<0.05）;the CD8,bilirubin,ALT and prothrombin time were（32.3±4.7） %,（42.7±21.5） μmol/L,（67±35） IU/L and（24.8±3.4）s,significantly higher than in spleen resection group（22.7±3.4） %,（29.2±12.4） μmol/L,（40±26） IU/L and （16.2±3.4）s（P<0.05）,or in with partial splenic artery embolization（23.0±3.6） %,（35.2±13.4） μmol/L,（56±20） IU/L and （16.5±2.9）s（P<0.05）;the incidences of subphrenic infection,pulmonary infection,pulmonary atelectasis,splenic vein inflammation,upper gastrointestinal bleeding were 43.3%,56.7%,26.7%,20.0%,23.3%,significantly higher than in spleen resection group (12.0%,14.0%,6.0%,4.0%,8.0%,P<0.05）,or in with partial splenic artery embolization (10.7%,14.3%,3.6%,3.6%,7.1%,P<0.05）. Conclusion The liver function improves in patients with liver cirrhosis after receiving splenectomy or partial splenic artery embolization.

Objective To investigate the efficacy of intrahepatic transplantation of autologous bone marrow mesenchymal stem cells （BMSCs） in the treatment of patients with decompensated alcohol-induced liver cirrhosis （ALC）. Methods Twenty-eight patients with decompensated alcohol-induced liver cirrhosis were recruited for intrahepatic transplantation of BMSCs from 2007 to 2012,and other 28 patients with ALC were selected by propensity scores matching for age,gender and complications of liver cirrhosis. Results The serum alanine aminotransferase levels declined to nearly normal levels,total bilirubin decreased,albumin（ALB） increased, prothrombin times shorten,and Child-Pugh scores（CPS） were improved gradually;The model of end stage liver disease scores were significant decreased to（20.6±5.2） at forth week,and significantly lower than in the control group（P=0.009）,however,there was no remarkable differences after 72 weeks （P=0.536） between the two groups;The survival rates at 144 weeks in the two groups were not significantly different （32.1% vs. 25.6%,P=0.125）;Further analysis showed that the survival rates in patients with CPS class B in the two groups were significantly different （66.7% vs. 36.4%,P=0.046）,while there was no significant difference in patients with CPS class C （12.5% vs. 17.6%,P=0.788）. Conclusions The short-term efficacy of BMSCs transplantation in the treatment of patients with decompensated ALC is favorable,but the long-term efficacy needs further investigation.

Objective To investigate the expression of cytokeratin-19（CK19） in primary liver clear cell carcinoma（PCCCL） and explore its implication for prognosis of patients with PCCCL. Methods The liver cancerous tissues from 76 individuals with HBV-associated PCCCL from 2006 to 2014 in Beijing You`An Hospital affiliated to Capital Medical University were retrospectively reviewed. The expressions of CK19,P53,CD34, glypican-3 （GPC-3）,HepPar-1 were detected by immunohistochemistry staining. Kaplan-Meier survival curves and Wilcoxon test were used to assess the prognosis between CK19-positive and negative patients. Results 9 （11.84%） out of 76 patients with PCCCL were found CK19 positive in tumor tissues;When tumors were greater than 3 cm,a distant metastasis were 60.0%（3/5） in CK19 positive cases,which was much higher than 8.7%（2/23,P<0.05）in CK19 negative cases;The patients with CK19 negative had longer （60 weeks） survival times than in patients with CK19 positive（31 weeks,P<0.05） as showed by the Kaplan-Meier survival curves and Wilcoxon tests. Conclusion PCCCL consists of a heterogeneous origin,and it may transformed from CK19 positive hepatic progenitor cells in the process of differentiation and maturation. The expression of CK19 in PCCCL is closely associated with the poor prognosis of patients with PCCCL.

Objective To clarify the prognostic factors that influence the overall survival（OS）in patients with hepatitis B virus-related primary liver carcer（HBV-PLC）. Methods The clinical data of 119 patients with HBV-PLC from November 2011 to June 2014 in our hospital were retrospectively reviewed,and OS was analyzed by using Kaplan-Meier method,Log-rank test and Cox proportional hazard model. Results There were 41 cases （34.5%） with terminal stage of tumor [Barcelona Clinic Liver Cancer（BCLC）stage D ],79（66.4%） with Child-Pugh class C,78（65.5%） with pre-existing diseases,and 90（75.6%） with tumor metastasis among the 119 patients with HBV-PLC;The median overall survival in this series was 287（172,560） days,and the median overall survivals of patients with non-antiviral therapy,with antiviral therapy for less than one year,with antiviral therapy for one to three years,and with antiviral therapy for more than 3 years were 232（114,390） days,357（179,879） days,530 （206-）days,and 795（384,912） days （P<0.01）;The Cox proportional-hazards model demonstrated that nationality [relative risk（RR）=3.18,95% CI,1.71~5.91,P=0.000],Child-Pugh class（RR=1.60,95%CI,1.180~2.16,P=0.002）,tumor metastasis（RR=4.86,95%CI,2.72~8.68,P=0.000）,age（RR=1.82,95%CI,1.13~2.95,P=0.014）,antiviral therapy prior to diagnosis of HBV-PLC（RR=1.30,95%CI,1.00~1.69,P=0.048）,serum HBV DNA level （RR=5.88,95%CI,3.22~10.71,P=0.000）and the way targeting tumor therapy （RR=1.13,95%CI,1.01~1.26,P=0.025） were significant predictor of overall survival. Conclusion Many factors might influence the overall survival of patients with HBV-PLC,and the rigorous screening and surveillance in the HBV-infected populations,and effective antiviral therapy for HBV infection are important for prolonging the life of patients with PLC.

Objective To explore the expression of heparanase（Hpa） in liver cancer tissues, and its relationship with the microvascular density（MVD）. Methods The Hpa mRNA levels in tumor, close-adjacent cancerous （group A） and peri-cancerous liver tissues （group B） from 47 patients with primary liver cancer were detected by RT-PCR. The expression of Hpa protein and CD34 in liver and cancer tissues were detected by immunohistochemistry. The correlation of Hpa mRNA to MVD in tissues with different clinical and pathological characteristics were analyzed. Results There were significant differences between Hpa levels in tumor tissues with different differentiation and clinical stages,with or without metastasis and recurrence,high or low AFP levels,with or without portal vein tumor emboli,and large or small tumor sizes （P<0.05）;The Hpa mRNA levels （0.793±0.184） and the MVD（34.5±12.2） in liver cancerous tissues were significantly higher than those in group A and group B （P<0.05）,while the Hpa mRNA levels and MVD in group A were significantly higher than those in group B [（0.577±0.145） vs. （0.384±0.117）,and （22.2±10.7） vs. （14.7±7.4）,respectively,P<0.05];The Hpa mRNA level in each group was positively correlated with MVD（r=0.627,P<0.05）. Conclusion Hpa plays an important role in the growth,invasion and angiogenesis of hepatocellular carcinoma.

Objective To investigate the clinical efficacy of cytokine-induced killer cells（CIK） combined with transcatheter arterial chemoembolization（TACE） for patients with primary liver cancer. Methods A total of 67 patients with primary liver cancer were enrolled in Daping hospital from February 2012 to February 2014. According to therapy choice,the patients were divided into combination treatment group（n=32,treated with CIK plus TACE） and control group（n=35,treated with TACE alone）. The peripheral T-lymphocyte subsets alterations, quality of life（QOL）,clinical efficacy and the progression-free-survival（PFS） after treatment were compared between the two groups. Results The proportions of CD3⁺T lymphocytes,CD4⁺T lymphocytes and CD4⁺/CD8⁺ ratio in peripheral blood were significantly increased 7 days after CIK treatment in combination therapy group [（70.32±2.36）% vs.（63.56±2.42）%,（32.18±2.27）% vs.（30.34±2.05）%,and（1.15±0.05） vs.（0.90±0.05）, respectively,P<0.05 for all];The proportion of CD8⁺T lymphocytes was significantly decreased in combination treatment group[（29.35±2.95）% vs.（33.28±3.14）%,P<0.05];Partial remission rate was higher in combination treatment group as compared with that in control group,but with no statistical difference（53.1% vs. 42.9%,P>0.05）;The median PFS was significantly different between the two groups（16 months vs. 9.5 months,P<0.05）;Adverse effects in combination treatment group were mild,and the symptoms disappeared after managements. Conclusions CIK combined with TACE therapy can significantly increase the cell immune function in patients with primary liver cancer than TACE therapy alone. it can improve the QOL and slow the progress of liver cancer in patients with hepatocellular carcinoma.

Objective To explore the efficacy of the gelatin sponge particle and embosphere microsphere embolization for the treatment of patients with hepatocellular carcinoma and tumor rupture. Methods 49 patients with rupture of hepatocellular carcinoma underwent transcatheter arterial embolization by gelatin sponge particle （n=23） or embosphere microsphere（n=26） embolization in recent 5 years,and instant hemostatic and rehaemorrhagia rates were compared. Results There was no difference between gelatin sponge particle and embosphere microsphere embolization on the effects of instant hemostatic（both were 100%）;Seven days after intervention,the rehaemorrhagia rate in gelatin sponge particles was 13.0%（3/23）,one patient was transferred to surgery,one patient was re-intervened and one patient dead because of haemorrhagic shock,respectively;The rehaemorrhagia rate in embosphere microspheres group was 3.8%（1/26,P<0.01）,and the patient received re-intervention and the bleeding was stopped successfully. Conclusion The instant hemostatic effect is the same between the gelatin sponge particle and embosphere microspheres embolization in patients with rupture of hepatocellular carcinoma,however,the embosphere group has much less chance to rebleeding within 7 days.

Objective To analyze iodine[¹³¹Ⅰ] metuximab injection combined with TACE treatment in recurrent patients with hepatocellular carcinoma （HCC） after naive TACE treatment. Methods From May 2013 to August 2014,58 patients with recurrent HCC after TACE treatment in our hospital were recruited in this study, and they were randomly divided into observation group and control group with 29 cases in each. The patients in control group were given conventional TACE,and in observation group were given iodine [¹³¹Ⅰ] metuximab injection combined with TACE. The efficacy,laboratory indexes and adverse reactions were compared in the two groups. Results The total effective rates in observation group and control group were 55.17% and 31.03%,respectively（P<0.05）;the serum albumin levels decreased significantly（P<0.05）,and bilirubin levels increased significantly（P<0.05） in the observation group one week after treatment as compared to those before treatment; the serum albumin levels dropped significantly （P<0.05）,and bilirubin levels increased significantly （P<0.05） in the control group too;the incidence of adverse reactions in observation group was 10.34%,and it was 3.45% in the control group;the 1 a survival rate in observation group was 55.17%,and it was 48.27% in the control（Log-rank=5.782,P=0.016）;the mean disease progression times in the observation and control groups were （4.83±4.10） m and （2.54±2.07） m,respectively （P<0.05）. Conclusion Iodine [¹³¹Ⅰ] metuximab injection combined with TACE in treatment of recurrent patients with HCC has a better efficacy than that of TACE alone,and it is safe and feasible.

Objective To investigate the clinical efficacy and safety of laparoscopic hard choledochoscopy and pneumatic ballistic lithotripsy in the treatment of patients with intrahepatic bile duct stones. Methods 69 patients with hepatolithiasis were randomly divided into the control group （n=34） and the observation group （n= 35） according to the operation they received. The patients in the control group received traditional surgery,and in the observation group received laparoscopic hard choledochoscope and pneumatic ballistic lithotripsy. Serum IgG,IgM and Ig A levels were detected. Results The operation time,blood loss,T tube removal time and gastrointestinal function recovery time in the observation group were（117.37±10.02） min,（115.32±10.08） mL, （18.55±3.86） h and（2.11±0.65） h,respectively,significantly different as compared to those in the control group [（159.39±12.17） min,（254.02±22.38） mL,（37.32±5.45） h and （3.73±1.07） h,respectively,P<0.05];the ambulation,flatus, hospital stay and residual stone occurrence were（4.90±0.71） d,（33.08±5.45） h,（16.53±3.07） d and 8.57% in the observation group, significantly different compared to those in the control group[（6.59±1.22） d,（58.02±10.11） h,（21.02±4.04） d and 50.00%,respectively,P<0.05];serum levels of IgG,IgM and IgA in the observation group after operation were significantly higher than in the control group（P<0.05）;the postoperative complication rate in the observation group was 11.43%,significantly lower than 35.29% in the control group（P<0.05）. Conclusion Compared with traditional surgery,laparoscopic hard choledochoscopy and pneumatic ballistic lithotripsy in the treatment of patients with hepatolithiasis has a good efficacy with low complications.

Hepatitis B virus（HBV） specific CD8⁺T cells play a crucial role in the pathogenesis of HBV infection. It is not only involved in the HBV inhibition and clearance,but also in the progress of the illness. Immune response is the key factor that determines whether HBV infection is gone or remained. This paper mainly discussed the latest research progress related to the phenotypes and functions of HBV specific CD8⁺T cells in the acute phase and chronic phase of HBV infection, and summarized updates on basic research of CD8⁺T cells,aiming at providing a further understanding of what roles CD8⁺T cells play in virus clearance at different stages of HBV infection. Meanwhile,we made an introduction of novel in vitro immune system model of HBV specific CD8⁺T cells,as well as innovative techniques to detect HBV-specific CD8⁺T cell,the advantage and significance of which is incomparable by any traditional methods.

Programmed cell death-1（PD-1）,as an inhibitory co-stimulatory molecule,is expressed on the surface of T lymphocyte membranes. After interacting with its main ligand,programmed death-1 ligand（PD-L1）,PD-1 decreases immune response of T lymphocytes,and even damages the overall functioning of T lymphocytes. PD-1/PD-L1 signaling pathway plays an important role in the tolerance of T cell immune response triggered by hepatitis B virus infection. Studies indicate that blocking this pathway may provide an new insights into antiretroviral therapy,and might be a promising applications in clinical practice.

Many patients with hepatocellular carcinoma （HCC） have no opportunity to undergo surgical treatment when diagnosed and HCC is not sensitive to radiotherapy and chemotherapy. Therefore,the overall curative effect of patients with HCC is far from satisfaction. Currently,in the experimental and clinical research on HCC biotherapy,cellular immunotherapy shows potential effects and great perspective. In this review,we summaried the recent advances in cellular immunotherapy for HCC.