Objective To preliminarily investigate the association of TRIM29 with HBV replication and the antiviral effect of pegylated interferon α-2b(PEG-IFN-α-2b),since TRIM29 protein is involved in the development and progression of a variety of diseases and is closely associated with the replication of some DNA and RNA viruses.Methods A total of 64 chronic hepatitis B(CHB)patients who attended the outpatient service of Department of Infectious Diseases,The Affiliated Hospital of Guizhou Medical University,from October 2021 to June 2022 were enrolled,among whom there were 34 treatment-na?ve patients and 30 patients treated with PEG-IFN-α-2b,and 30 healthy volunteers in Physical Examination Center were enrolled as controls.Related data were collected,including age,sex,alanine aminotransferase,aspartate aminotransferase,total bilirubin,direct bilirubin,HBV DNA,and peripheral blood mononuclear cells(PBMCs).HepG2 and HepG2.2.15 cells were used as cell models and were transfected with TRIM29-specific overexpressed plasmid or siRNA and control plasmid.HepG2 cells and Huh7 cells were treated with PEG-IFN-α-2b(0,10,100,1 000,and 10 000 U/mL),and HepG2.2.15 cells were treated with TRIM29-specific siRNA or negative control combined with PEG-IFN-α-2b.ELISA was used to measure the concentrations of HBsAg and HBeAg;qRT-PCR was used to measure the relative expression levels of TRIM29 and HBV RNA;Western blot was used to measure the protein expression levels of STING,p-TBK1,TBK1,pIRF3,IRF3,MX1,and IFIT1;co-immunoprecipitation assay was used to observe the interaction between TRIM29 and STING protein.The independent-samples t test was used for comparison of normally distributed continuous data between two groups,and a one-way analysis of variance was used for comparison between multiple groups,with the least significant difference t-test for further comparison between two groups;the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups.Results The CHB patients had a significantly higher expression level of TRIM29 in peripheral blood than the healthy controls(P<0.001).In cell experiments,the expression levels of HBsAg,HBeAg,and HBV RNA increased with the upregulation of TRIM29 expression and decreased with downregulation of TRIM29 expression(P<0.05).TRIM29 bound to STING and degraded STING via protease,and compared with the control group,there were no significant changes in the total protein levels of TBK1 and IRF3 after overexpression of TRIM29,while there were significant reductions in the expression levels of STING,p-TBK1,and p-IRF3(P<0.05).The protein and mRNA expression levels of TRIM29 decreased with the increase in the concentration of PEG-IFN-α-2b for the treatment of HepG2 and Huh7 cells(P<0.01).During the treatment with PEG-IFN-α-2b,the CHB patients had a gradual reduction in the mRNA expression level of TRIM29,and there was a significant difference between the early response group and the non-response group(P<0.05).In the context of treatment with an equal volume of PEG-IFN-α-2b,compared with the control group,there were significant increases in the protein expression levels of Mx1 and IFIT1 in HepG2.2.15 cells after TRIM29 knockdown(P<0.05).There was a gradual reduction in the expression of TRIM29 in CHB patients during the early stage of PEG-IFN-α-2b treatment.Conclusion TRIM29 targets and degrades STING and promotes HBV replication by inhibiting the STING-TBK1-IRF3 signaling pathway.TRIM29 interferes with the antiviral effect of PEG-IFN-α-2b,and the expression level of TRIM29 in PBMCs of CHB patients may be used as an indicator for predicting the response of patients to PEG-IFN-α-2b therapy.

Objective:To study the curative effect of rehmannia glutinosa leaves total glycoside capsules and the role of mitochondrial autophagy on nucleos(t)ide drug-induced renal injury.Methods:Adefovir dipivoxil (ADV) was used to construct a hepatitis B virus (HBV) transgenic mouse model for renal injury. Renal function was measured in each group at one and two weeks of modeling. Mitochondrial autophagy indicators were measured at two weeks of modeling in renal tissue. Transmission electron microscopy was used to detect mitochondrial autophagy phenomena in renal tissue. The model was established for two weeks. Mouse with renal injury were treated with rehmannia glutinosa leaves total glycoside capsules or isotonic saline for eight weeks by intragastric administration. Renal function was measured. Renal tissue morphology was observed. Mitochondrial autophagy indicators were detected in renal tissue. The protective effect of different concentrations of verbascoside (the main active ingredient of rehmannia glutinosa capsule) was observed on HK-2 cell damage induced by ADV. HK-2 cells were divided into control, ADV, and ADV plus verbascoside groups. The effects of verbascoside at different times and concentrations were observed on the HK-2 mitochondrial autophagy indicators. Fifty patients with chronic hepatitis B were collected who presented with renal injury after treatment with nucleos(t)ide analogs. The random number method was used to divide 29 cases into a control group that received conventional treatment. The treatment group of 21 cases was treated with rehmannia glutinosa leaves total glycoside capsules on the basis of the control group. Serum creatinine (Scr) and urinary protein were detected at eight weeks.The χ2 test or t-test was used for statistical analysis. Results:Compared with the control group, two weeks of modeling in the ADV group induced renal function injury in HBV mice. The expression of autophagy indicators was higher in the renal tissue of the ADV group than that of the control group. Transmission electron microscopy had revealed mitochondrial autophagy in the renal tissue of the ADV group. Compared with the control group, the renal function of HBV mice treated with rehmannia glutinosa leaves total glycoside capsules improved for two months, and the expressions of autophagy indicators were down-regulated.Verbascoside promoted proliferation in ADV-damaged HK-2 cells, and the expression of autophagy indicators was down-regulated compared with the ADV alone group. In 50 patients with renal function injury, the urinary protein improvement was significantly superior in the treatment group than that in the control group, with eighteen and three cases being effective and ineffective in the treatment group and 12 and 17 cases being effective and ineffective in the control group, with a statistically significant difference ( χ2 ?=?9.975 0, P ?=?0.001 6). Serum creatinine was decreased in the treatment group compared with the control group, with 11 and 10 cases being effective and ineffective in the treatment group and 12 and 17 cases being effective and ineffective in the control group, with no statistically significant difference ( χ2 ?= 0.593 5, P ?=?0.441 1). Conclusion:Rehmannia glutinosa leaves total glycoside capsule can improve the nucleos(t)ide drug-induced renal function injury in chronic hepatitis B, possibly playing a role via inhibiting PINK1/Parkin-mediated mitochondrial autophagy.

Objectives Comparative analysis on epidemiological characteristics of measles in Minhang District before and after Large scale supplementary immunization activities of measles containing vaccine(MCV) in 2010. Methods Measles incidence data of MCV-SIA in 2010 and the first five years before 2010 (from January 1, 2005 to December 31, 2009), the next five years (from January 1, 2011 to December 31, 2015) and the second five years (from January 1, 2016 to December 31, 2020) after were collected. Descriptive epidemiological method was used for comparative analysis. Results The incidence rate of measles in Minhang District, Shanghai after MCV-SIA in 2010 showed a significant downward trend, The average annual incidence (per 100 0000) in the first 5 years before 2010 was 155.96, SIA was 30.08,The next five years was 29.52, The second five years was 2.84,There was statistical difference in the annual incidence rate between the four groups.（χ²=3165.821，P<0.01）. The annual incidence rate between registered residence and non registered residence population were not statistically different after second SIA years after the SIA（χ²=1.646，P=0.223）The proportion of 8-month-old children under the age of MCV decreased from 15.46% in the first five years of MCV-sia to 5.88%,In the second five years after MCV-sia, the proportion of 10-14 age group increased from 7.81% to 13.83%, The susceptible population of measles before MCV-SIA was less than 8 month old and under the age of MCV initial immunization, no migrant workers with no history of immunization and adults with registered residence. Once there is a source of infection, it is easy to cause the spread of the epidemic. After MCV-SIA, foreign students in international schools and nonworking population became the focus of measles. Of the 95 cases in which measles virus genotypes were available in the next five years, 2 (2.11%) were A genotype, and 93 (97.89%)were the indigenous H1 genotype ; Of the 7 cases in which measles virus genotypes were available in the second five years,7 (100%)were the indigenous H1 genotype . Conclusions After MCV-SIA, the comprehensive measles prevention and control measures can effectively control the incidence and prevalence of measles in Minhang District. But circulation of the indigenous H1 genotype was not interrupted, the work of normalization measures to eliminate measles also needs to cooperate with many departments to strengthen the prevention and control measures of measles in foreign schools and the nonworking population.

Objective: To observe the effects of blueberry and nuclear expression of transcription factor-кb (NF-кb) p65 in an experimental rat model of liver fibrosis. Methods: Forty-five Sprague-Dawley rats were randomly divided into isotonic saline control group (A); model group (B); blueberry juice prevention group (C, 15 g/kg); dan-shao-hua-xian capsule prevention group (D, 1 g/kg); and blueberry juice + dan-shao-hua-xian capsule prevention group (E). Rat liver fibrosis model was established by covalent compound carbon tetrachloride (CCl₄). Each prevention group was given the corresponding dose of blueberry juice or (and) dan-shao-hua-xian capsule, and the rats were sacrificed after 8 weeks. The degree of liver fibrosis was evaluated by hematoxylin and eosin stain. A liver tissue of NF-κBp65 was detected by immunohistochemical method. The NF-κBp65 protein expression of liver tissue and transforming growth factor (TGF) β1 was detected by Western blot. Data of multiple groups were compared by one-way analysis of variance, and rank sum test. Results: Immunohistochemistry detected that TGFβ1 protein was mainly expressed in mesenchymal origin of hepatic stellate cells. The expression level of group A (3.75 ± 1.67) was low, while those of group B (9.00 ± 2.07), C (7.33 ± 1.00), D (6.00 ± 1.51), and E (3.5 ± 1.41) were high. However, the expression level of TGF-β1 protein in hepatic tissues of group B was significantly higher than that of group C, D and E [group E: 3.5 ± 1.41, F = 18.350, P < 0.05]. In addition, group D was higher than group E (P < 0.05). The expression of NF- kappa Bp65 protein was very complex, and the expression patterns in different groups were different (Statistical calculation of experimental data were based on expression of liver cells). Compared with group B (4.37 ± 2.13), the relative expression levels of NF-κBp65 protein in-group A (0.46 ± 0.25), group C (2.76 ± 1.01), group D (2.13 ± 1.51), group E (1.88 ± 0.99) were significantly decreased (F = 27.490, P < 0.05), and the expression trend was consistent with TGFβ1 protein. Western blot detected NF-κBp65 protein in liver tissues of rats. Compared with group A, levels in groups B, C, D and E were significantly increased (F = 96.983, P < 0.05), and groups C, D and E were significantly lower. The E group was significantly lower than the C group (F = 96.983, P < 0.05), and the degree of hepatic fibrosis was lower in each prevention group than in the B group (T = 24.1, P < 0.05). Conclusion Blueberries have preventive effect on CCl4-induced hepatic fibrosis in rats, and its preventive mechanism may inhibit the expression and activation of NF-κBp65 in hepatocytes, thereby reducing TGFβ1- mediated production or activation.

Objective: To observe the efficacy and safety related measures by blocking mother-to-child transmission of hepatitis B virus with high viral load and HBeAg positivity during pregnancy in Guizhou province. Methods: Outpatient and inpatient cases of the Department of Infectious Diseases and Obstetrics of Guizhou Medical University Affiliated Hospitals from May 2016 to July 2017 were retrospectively divided into intervention group, non-intervention group and non- hepatitis B pregnant women group; with 75 cases in each group. HBsAg and HBeAg were positive in the intervention group. Pregnant women with HBV DNA ≥10⁶ IU/ml were treated with anti-HBV therapy for 24 to 28 weeks of gestation until delivery. According to oral drugs, they were divided into tenofovir (TDF) group or telbivudine (LDT) group, non-intervention group (HBsAg and HBeAg positive), HBV DNA positive pregnant women, pregnant women with no anti-HBV drugs, non-hepatitis B pregnant women (normal pregnant women without HBV infection). Infants and young children born to the three groups of women were immunized with the national viral hepatitis B action plan. The gestational weeks and Apgar scores at birth, delivery mode, feeding mode, sex and 7-months-old age were observed and counted. Serum hepatitis B markers (HBVM) and HBV DNA were quantitatively detected. HBVM was detected by time-resolved fluorescence immunoassay (TRFIA), and HBV DNA was detected by real-time PCR (FQ-PCR). The changes of liver parameters, HBsAg, HBeAg, HBV DNA, adverse drug reactions and treatment response of pregnant intervention group before medication (12-24 weeks of gestation), 4 weeks of medication (28-32 weeks of gestation), 36-40 weeks of gestation (36-40 weeks of gestation) were statistically calculated. A t-test was used to compare the data between the measurements. Data measurements within the groups were analyzed using rank -sum test. Results: In the intervention group, therapeutic medications showed no differences in demographic and clinical characteristics between TDF group and LDT group, including liver parameters, HBsAg, HBeAg and log10HBV DNA level. Compared with pre-treatment (TDF group: 4.84 ± 2.01; LDT group: 5.08 ± 1.99), TDF and LDT were significantly lower at the end of pregnancy (TDF group: 3.06 ± 0.66; LDT group: 3.51 ± 1.20). P < 0.05); and the treatment response rate was 100%. There were no serious adverse events in the intervention group. Infants and young children (7-months-old) in the intervention group had negative HBsAg, HBeAg and HBV DNA. The mother-to-child transmission rate of HBV was zero, with blocking rate of 100%. In addition, both infants and young children had different degrees of hepatitis B protective antibodies (anti-HBs, M: 144.33), and their antibody titers were higher than that of non-intervention group (anti-HBs, M: 65.91) and non-hepatitis B pregnant women (anti-HBs, M: 58.43). The difference was statistically significant (P < 0.05), and there was no significant correlation between the use of antiviral and the way of delivery and feeding. Outcomes of mother-to-child transmission of HBV infection in infants and young children (7-months-old) delivered by three groups of pregnant women in the non-intervention groups had 20.0% (15/75)/ 17.3% (13/75) HBsAg/HBeAg positivity rate, and 17.3% (13/75) HBV DNA positivity rate. Overall, mother-to-child transmission rate of HBV infection was 20% (15/75). Furthermore, the relationship between mother's HBV DNA load and infant HBV infection in the non-intervention group showed mother's HBV DNA ≥10⁶ IU/ml. Conclusion In the non-intervention group, mother-to-child transmission of HBV occurred, and infected mothers HBV DNA was ≥106 IU/ml before delivery. This suggests that HBeAg positive and high load HBV DNA replication were independent risk factors for mother-to-child transmission of hepatitis B. Therefore, prenatal drug intervention and postpartum standard immune blockade are necessary for high-risk pregnant women with hepatitis B to achieve zero mother-to-child transmission of hepatitis B in real- clinical practice.

Objective To analyze the genetic characteristics of breakthrough varicella-zoster virus infection during the varicella outbreaks in Minhang District of Shanghai in 2013-2014. Methods Samples of the varicella-zoster liquid were collected from patients with chickenpox in Minhang District in 2013-2014 and used for the extraction of genomic DNA. The open reading frame ( ORF) of 22 and 62 regions were se-quenced and further analyzed by using bioinformatics methods. Results A total of 24 samples were success-fully collected and sequenced, and all of them were wild strains. Among the 24 varicella-zoster virus strains, 23 strains were highly homologous to the parental strain ( P-Oka) and the vaccine strain ( V-Oka) , indica-ting that they belonged to J genotype. Only one strain, whose genotype was between M and E, was highly ho-mologous to the mosaic( M) CA123 strain ( M1 genotype) , indicating that it might belong to M1 genotype. Conclusion The epidemic strains of varicella-zoster virus in Minhang District were mainly J genotype. Lo-cal epidemic of M and other genotypes of varicella-zoster virus also existed. There were some gene variations in different strains of J genotype. These varicella-zoster virus strains of non-vaccine genotypes might be one of the reasons causing the breakthrough cases of chicken pox.

Objective To evaluate the epidemiological efficacy of 23-valent pneumococcal poly-saccharide vaccine on the clinical symptoms and the incidence of respiratory tract infections in the elderly over 60 years old in Minhang District, Shanghai. Methods A prospective cohort study was conduct, in which the sample size was 1 200 for both inoculated and uninoculated groups. This study followed the two groups of subjects every quarter for a year. Clinical symptoms and the incidence of respiratory tract infectious diseases as well as the acute onset of chronic respiratory diseases were compared between the subjects of the two groups. Results Compared with the uninoculated group, less people in the inoculated group developed the clinical symptoms of respiratory tract infection (RR=0. 894, 95% CI: 0. 804-0. 994). Immunization with the 23-valent pneumococcal polysaccharide vaccine protected 57. 7% of the senior citizens (≥75 years old) from respiratory tract infections(95% CI:0. 207-0. 775). Conclusion The 23-valent pneumococcal polysaccharide vaccine can effectively reduce the incidence of respiratory tract infections in the elderly aged 60 years old and over and protects the elderly aged 75 years old and over from respiratory tract infections. Further studies on the immunological efficacy of 23-valent pneumococcal polysaccharide vaccine should be carried out by measuring the antibody titers before and after vaccination.

Objective To measure the titers of varicella live attenuated vaccines ( VarV) during the process of transportation and storage in different seasons and communities of Minhang Distract, Shang-hai, to evaluate the operation of cold chain system and the thermal stability of vaccines and to provide refer-ences for the management, introduction, research and development of vaccine in future.Methods Four communities with high outbreak rates of varicella during 2012 to 2013 and four communities with low out-break rates were randomly selected from 13 communities in Minhang District, Shanghai.The titers of VarVs were detected by using the quantitative plaque assay before and after 30 days of storage in November 2013 and February, May, August 2014.Results The overall rate of qualified VarVs was 90.63% with a geo-metric mean titer (GMT) of 3.67 (LgPFU/0.5 ml).96.88%of the VarVs produced by company C met the quality standard with a GMT of 3.89 ( LgPFU/0.5 ml) followed by those produced by company B with a rate of 91.67%and a GMT of 3.75 ( LgPFU/0.5 ml) .The rate of qualified VarVs produced by company A was the lowest, which was 80.00%, with GMT of 3.29 (LgPFU/0.5 ml).There were significant differences in the rates of qualified VarV among the three companies (χ2=8.288, P=0.016).The rate of qualified vac-cines in communities close to the Shanghai Minhang Center for Disease Control and Prevention ( Minhang CDC) was 91.67%, while 100%of the vaccine samples collected form the communities at a middling dis-tance from or far from the Minhang CDC met the quality standard.No significant difference in the rate of qualified vaccine was found among the three types of communities (χ2=3.441, P=0.179).The quarterly rates of qualified vaccines produced by B and C companies were 100%except for the third quarter.The rates of qualified vaccines produced by A, B and C companies in the third quarter were respectively 70.00%, 66.67%and 87.50%.No statistical differences in the quarterly rates of qualified vaccines were found among the three companies (χ2=1.25, P=0.7412;χ2=6.545, P=0.088; χ2=6.194, P=0.103).No statistical differences in the rates of qualified vaccines before and after 30 days of storage were found among the three companies (χ2=0.625, P=0.347;χ2=0.000, P=1.000;χ2=2.065, P=0.492).Conclusion A well-managed and-operated cold chain system was implemented in Minhang District in the storage and transport of vaccines as well as other related links.The thermal stability of vaccines produced by company C was better than those of the other two companies.A surveillance for the titers of vaccines produced by com-pany A should be strengthened.