Objective To investigate the associated factors of complete virological response (CVR) in Entecavir treatment among chronic hepatitis B (CHB) patients with positive HBeAg.Methods Data of 166 CHB patients with positive HBeAg receiving Entecavir treatment in Yantai Infectious Diseases Hospital during December 2009 and May 2014 were collected.Clinical data including age,gender,genotype,baseline alanine aminotransferase (ALT),HBV DNA load,HBsAg and HBeAg levels as well as CVR cumulative rates at different time points during Entecavir treatment were retrospectively analyzed.The cumulative rate of CVR was estimated using Kaplan-Meier method,and the difference in cumulative CVR rates was studied with Log-rank test.Cox's proportional hazards regression model was used to analyze the factors associated with CVR during Entecavir treatment.Results The cumulative rates of CVR during Entecavir treatment in HBeAg positive CHB patients were 54.5％ (87/157),74.3％ (106/129),80.2％ (109/119) and 86.8％ (110/112) at 48,96,144 and 192 weeks,respectively.Log-rank test showed that female patients and patients with genotype B,high baseline ALT level or low baseline HBV DNA load had higher CVR rates (x2 =15.601,11.542,17.021 and 10.094,all P ＜ 0.01).Cox's proportional hazards regression model showed that female was the only associated factor for CVR in Entecavir treatment among HBeAg positive CHB patients [hazard ratio (HR) =3.015,95％ confidence interval (CI):1.875-4.968,P ＜ 0.01].Conclusion CVR rate is increasing with the course of Entecavir treatment in HBeAg positive CHB patients,and CVR is more likely to occur in female patients.

Objective To investigate the impact of steatosis on liver stiffness (LS) detected by transient elastography (Fibroscan) in patients with chronic hepatitis B (CHB).Methods 303 cases of CHB who underwent liver pathology and Fibroscan from January 2010 to May 2013 were retrospectively analysed.Biochemical parameters were collected.LS values in patients of CHB with and without steatosis were compared.LS values in patients of the same stage of liver fibrosis combined with different degrees of steatosis were compared using ANOVA.Cut-off values were obtained by Receiver Operating Characteristic (ROC curve) analysis.Results 273 cases were included when excluding BMI ＞ 28 kg/m2 and ALT ＞200U/ml.Steatosis was present in 75 (31.6％) cases,steatosis was absent in 162 (68.4％) cases.In every stage of fibrosis,combining with steatosis has no significant impact on LS values.LS(kPa) were 5.3 ±1.4vs5.9±1.9,9.5±4.2 vs8.7 ±3.0,18.4 ±7.5 vs 15.0 ±6.6,21.4 ±7.5 vs27.6±5.9 kPa,respectively.(P ＞ 0.05).While in the degree of F2,LS values in patients combined with the steatosis (S2) were higher than those in patients without steatosis (S0) (P ＜ 0.05) and with mild steatosis (S1) (P ＜0.05).LS values(kPa) were 11.28 ±5.54,8.68 ±2.95,8.12 ±2.44,respectively.Conclusions LS values have no significant difference in patients of CHB with steatosis and without steatosis with different degree of liver fibrosis.In patients with fibrosis stage of F2,LS values in those combined with moderate steatosis (S2) were higher than those without steatosis and with mild steatosis.

Objective:To analyze the clinical and laboratory features of patients with Coronavirus Disease 2019(COVID-19), for providing reference for the diagnosis and treatment of the disease.Methods:The clinical data of 72 patients confirmed as COVID-19 in Qishan hospital during January 23, 2020 to February 13, 2020 were collected. The data included the general information, clinical manifestations, laboratory tests and CT findings of the lungs. According to the severity of the disease, the patients were divided into the non-severe group and the severe group, and the laboratory tests characteristics of the two groups were compared. SPSS 22.0 statistical software was used for data analysis.Results:In the 72 patients, 40 were males and 32 females, the average age was (46.0±14.8) years. The main clinical manifestations were fever (84.7%) and cough (77.8%). Among them, 45 cases (62.5%) had expectoration with a small amount of white sticky sputum. The main laboratory results showed that lymphocyte count decreased in 26 cases (36.1%), the absolute number of T lymphocytes decreased in 18 cases (25.0%), CD4 + T cell count decreased in 8 cases (11.1%), CD8 + T cell count decreased in 14 cases (19.4%), ESR increased in 42 cases (58.3%), and CRP increased in 31 cases (43.1%). Peripheral blood lymphocyte (L), albumin, CD4 + T cell, CD8 + T cell, T-lymphocyte in severe group (n=61) were lower than those in non-severe group (n=11), while C-reactive protein (CRP), serum amyloid A (SAA), erythrocyte sedimentation rate (ESR), fibrin (FIB), aspartate aminotransferase (AST), creatine kinase (CK), lactate dehydrogenase (LDH) in severe group were higher than those in non-severe group ( P<0.05). In 72 patients, the negative time of the twice nucleic acid detection from nasopharyngeal swabs and sputum specimens were (21.48±7.9) days and (27.79±7.4) days, there were significant differences between the two groups of specimens for two consecutive negative times ( t=-4.532, P=0.000). The main pulmonary imaging manifestations of COVID-19 patients: two lungs in 58 cases, patchy opacities in 51 cases and ground glass shadows in 61 cases. Conclusions:Most of the COVID-19 patients in Yantai and Weihai were common type. The abnormal T lymphocyte, subcohorte and other laboratory indicators may indicate that the patients are more serious.

Recurrence rate after cessation of nucleos(t)ide analogues remains high in clinical practice. According to current evidences, age, HBsAg level, HB VRNA level, time of consolidation therapy and HBV DNA load were considered to be associated with off-treatment responses after cessation of nucleos(t)ide analogues. Combinative factors of several predictors might perform better in future accompanying with further studies of HBV related markers.

Objective To compare the cumulative rate of HBeAg seroconversion in HBeAg positive chronic Hepatitis B patients treated with telbivudine and entecavir after Propensity Score Matching.Methods CHB patients who accepted telbivudine or entecavir from Dec 2009 to May 2014 were retrospectively collected.PSM function of SPSS software was conducted to reduce confounding bias between the groups.And then survival analysis was performed for the matched data.Results 56 pairs of patients were successfully matched.The 2-year cumulative rate of HBeAg seroconversion were 28.6％ and 14.8％ in the telbivudine group and entecavir group,which were 42.0％ and 39.3％ in the fourth year respectively.Cox regression analysis revealed that telbivudine therapy,low HBeAg level at baseline were independent predict factors of HBeAg seroconversion(P ＜ 0.05).Conclusions The balance of covariates may be achieved through PSM.The 2-year cumulative rate of HBeAg seroconversion in the telbivudine group is higher than entecavir group,while they are similar in the 4th year.

Objective:To investigate the epidermal growth factor receptor (EGFR) mutation rate, mutation characteristics and distribution characteristics of different mutation types in patients with non-small cell lung cancer (NSCLC) in Fuyang of Yunnan province, to provide the clinical individualized targeted therapy of NSCLC in this region.Methods:A total of 328 NSCLC patients whose native place were Fuyuan and who underwent EGFR test in Fuyuan County People's Hospital in Yunnan Province from January 2018 to August 2020 were selected, and their clinical data such as gender, age, ethnicity, pathological type and the results of EGFR test were collected for statistical analysis.Results:The EGFR mutation rate of NSCLC patients was 40.55% (133/328). The EGFR mutation rate of female patients was higher than that of males ( P < 0.01). The EGFR mutation rate showed a downward trend with age, the EGFR mutation rate of patients ≤ 60 years old was higher than that of patients > 60 years old ( P = 0.014). The EGFR mutation rate in ethnic minority was not statistically different from Han nationality ( P = 0.789). The EGFR mutation rate of patients without smoking history was higher than that of patients with smoking history ( P<0.01). Patients with adenocarcinoma had a higher EGFR mutation rate than squamous cell carcinoma ( P = 0.002). The EGFR mutation rate in patients with stage Ⅰ-Ⅱwere higher than that in patents with stage Ⅲ-Ⅳ ( P = 0.013). The EGFR mutation rate in tissue samples were higher than that in peripheral blood samples ( P = 0.009). In 328 patients the EGFR single-point mutation rate was 24.70% (81/328), and the compound mutation rate was 15.85% (52/328); the common mutation rate was 17.07% (56/328), and the rare mutation rate was 23.48% (77/328). The top 5 mutation types were L858R (10.06%), G719X+S768I (7.32%), 19-Del (7.01%), G719X+L861Q (6.40%), and G719X (4.21%). In 133 patients with EGFR mutation, the proportion of patients with rare mutation [57.89% (77/133)] was higher than the proportion of patients with common mutation [42.11% (56/133)]. Conclusion:The EGFR mutation rates of female, adenocarcinoma, non-smoking and young NSCLC patients in Fuyuan area are high, and the rare mutation rate is high.

Objective To observe the effects of Yiqi Jiedu Compound on TCM syndrome score and immune regulation of Th17/Treg cells in peripheral blood of patients with myasthenia gravis.Methods 63 patients with myasthenia gravis were randomly divided into the control group(n=31)and the treatment group(n=32).The control group was given the basic treatment of pyridostigmine bromide and glucocorticoid and so on,and the treatment group was given Yiqi Jiedu Compound based on the control group.The two groups were treated for 12 weeks.Clinical efficacy was observed,TCM syndrome scores were statistically analyzed,and the expression levels were detected,which Th17/Treg cells,Foxp3/RORγ t gene and IL-6 and IL-17 cytokines in peripheral blood of patients in both groups before and after treatment.Results After 12 weeks of treatment,compared with the control group,the TCM syndrome score of patients in the treatment group was significantly decreased(P<0.05),and the expression of Foxp3 and Treg genes in peripheral blood was promoted(P<0.05),and the expression of Th17 and Treg cells and IL-6 and IL-17 cytokines in peripheral blood was decreased(P<0.05).Conclusion Yiqi Jiedu Compound may regulate the immune balance of Th17/Treg cells by affecting the differentiation of Th17 and Treg cells in peripheral blood and the expression levels of transcription factors RORγ t and Foxp3 genes and related cytokines,thus achieving the effect of myasthenia gravis treatment.

Objective: To investigate the efficacy of enticavir and lamivudine in preventing rituximab-associated hepatitis B virus(HBV) reactivation in patients with B-cell non-Hodgkin lymphoma complicated with resolved hepatitis B during chemotherapy. Methods: This retrospective study included 216 B-cell non-Hodgkin lymphoma patients with complete data from January 2012 to January 2018 treated in 3 hospitals.Of 78 patients with resolved hepatitis B, they were divided into lamivudine prophylactic group(17 cases), entecavir prophylactic group(11 cases) and control group(50 cases). The changes of HBVM, HBV DNA and liver function before or after rituximab combination chemotherapy were analyzed.The incidence of HBV reactivation, liver function injury and chemotherapy delay were compared. Results: Compared to the other 71 patients, 7 cases experienced HBV reactivation in 78 patients with resolved hepatitis B. There were no statistically significant differences between the two groups in patient demographics, pathological pattern, chemotherapy regimen.Six patients in the control group developed HBV reactivation(12%) and 1 patient in lamivudine prophylactic group(5.88%), none had HBV reactivation in enticavir prophylactic group.There was statistically significant difference among three groups(Fisher P=0.016). A total of 7 cases experienced HBV reactivation in 78 patients with resolved hepatitis B respectively, 2 cases in the first chemotherapy period, 2 cases in the third chemotherapy period, 1 case in the fifth chemotherapy period, the last one occurred after the completion of chemotherapy.Four patients had HBsAg reverse seroconversion, occurred in the 1, 3, 5 cycles during and after the completion of chemotherapy.Twenty patients (40.0%) experienced liver function parameters abnormal in the control group, 4 cases(23.5%) in lamivudine prophylaxis group, 2 cases (18.2%) in enticavir prophylaxis group during chemotherapy. Conclusion Antiviral prophylaxic therapy can potentially prevent rituximab associated HBV reactivation in patients with resolved hepatitis B. Entecavir can more reduce the risk of rituximab associated HBV reactivation than lamivudine.

Chronic hepatitis B (CHB) is a global epidemic disease caused by hepatitis B virus that can lead to hepatic failure, even liver cirrhosis and hepatocellular carcinoma. The occurrence and development of CHB are closely related to the changes in the gut microbiota communities. To explore the relationship between the structure of gut microbiota and liver biochemical indicators, 14 CHB patients (the CHB group) and 11 healthy people (the CN group) were randomly enrolled in this study. Our results demonstrate that CHB caused changes in the gut microbiota communities and biochemical indicators, such as alanine transaminase, total bilirubin and gamma glutamyl transferase. Furthermore, CHB induced imbalance of the gut microbiota. Prevotella, Blautia, Ruminococcus, Eubacterium eligens group, Bacteroides uniformis and Ruminococcus sp. 5_1_39BFAA were associated with the critical biochemical indicators and liver injury, suggesting a new approach to CHB treatment.
Bacteroides ; Eubacterium ; Gastrointestinal Microbiome ; Hepatitis B virus ; Hepatitis B, Chronic ; Humans ; Liver Cirrhosis ; Liver Neoplasms

Objective: To determine the changes in peripheral plasma concentrations of interleukin-10 (IL-10), interleukin -12 (IL-12) and interfoeron-γ(IFN-γ) in the patients with chronic hepatitis B virus (HBV) infection and their correlations with HBV infection stage or HBV DNA load of HBV carriers. Methods: Data of 135 patients with chronic HBV infection from March 2016 to March 2017 were collected, the patients included 32 chronic HBV carriers, 61 with chronic hepatitis and 42 with cirrhosis. Forty healthy subjects served as controls. The concentrations of IL-10, IL-12 and IFN-γ were determined using enzyme-linked immunosorbent assay (ELISA). Correlation analysis was performed using the Pearson correlation test, which was performed to analyze the correlation between IL-10, IL-12, IFN-γ and HBV infection stage, HBV DNA load of HBV carriers. Results: Compared with those in healthy controls, plasma IL-10 and IL-12 levels in patients with chronic hepatitis and cirrhosis increased significantly (F=22.06, 15.67, P=0.013, 0.021), plasma IL-10 and IL-12 levels in cirrhosis cases were higher than those in chronic hepatitis (all P<0.001), plasma IL-10 and IL-12 levels in chronic hepatitis were higher than those in chronic HBV carriers (all P<0.001). Plasma IFN-γ level in chronic HBV carriers, chronic hepatitis and cirrhosis were significantly higher than those in healthy controls (F=18.36, P=0.017). There were statistically significant differences in IFN-γ levels among the three groups in the chronic HBV carriers, chronic hepatitis and cirrhosis. IL-10, IL-12 and IFN-γ levels of the low, medium and high HBV DNA load groups were statistically significant (all P<0.05). There was no correlation between IL-10 and HBV DNA. IFN-γ, IL-12 and HBV DNA load were negatively correlated. There was no correlation between IL-10 and IFN-γ (r=0.103, P>0.05), IL-12 and IFN-γ were significantly positively correlated (r=0.687, P<0.05). Conclusions IL-10, IL-12 and IFN-γ may play an important role in the chronic HBV infection.