ABSTRACT
A lack of effective drugs and technical means to eradicate hepatitis B virus (HBV) is a bottleneck that limits the ability to fully cure HBV infection. Recently, genome-editing technology based on clustered regularly interspaced short palindromic repeats -associated protein 9 is an emerging technique for editing specific gene loci, which can specifically target HBV covalently closed circular DNA, effectively inhibits HBV DNA replication and regulates HBV functional protein expression, and is expected to become a powerful gene therapy tool for the complete eradication of HBV. Considering this, it has become the focus of attention for scholars at home and abroad that how to use clustered regularly interspaced short palindromic repeats -associated protein 9 to accomplish modification of HBV genomes for complete eradication of HBV. This paper summarizes the latest progress based on the latest research results at home and abroad in the application of clustered regularly interspaced short palindromic repeats -associated protein 9 gene editing technology in anti-HBV infection treatment, and expounds its potential and challenges as a radical cure for HBV infection.
ABSTRACT
Objective@#To investigate the knowledge of nonalcoholic fatty liver disease (NAFLD) among medical staff and general population in Hebei Province, China, understand the degree of awareness of NAFLD among residents, standardize the diagnosis and treatment of NAFLD, improve the correct awareness of NAFLD among general population, promote the establishment of a reasonable lifestyle, and scientifically and effectively control the incidence and mortality rates of NAFLD.@*Methods@#The investigation was performed in 30 hospitals and neighboring schools and communities in Hebei Province, and a questionnaire survey on the knowledge of NAFLD was performed for 1 300 medical workers and 2 000 persons from the general population. EpiData3.1 software was used to input data, and SPSS21.0 was used for statistical analysis. The chi-square test was used for comparison of rates between groups.@*Results@#Of all medical staff, 39.0% knew that liver biopsy was the gold standard for the diagnosis of NAFLD; 63.7% thought liver biopsy had the highest diagnostic value, followed by liver ultrasound (61.0%) and liver CT (48.1%); only 1.2% thought improvement of insulin resistance was the preferred treatment for NAFLD. Among 486 medical workers who had participated in the diagnosis and treatment of NAFLD, only 1.2% thought that the patients had good compliance. Of all persons from the general population, 15.2% thought NAFLD was infectious and 58.6% thought NAFLD might progress to liver cirrhosis or liver cancer. Of all respondents with body mass index ≥28 kg/m2, 17.8% did not know that he/she had obesity, and as high as 55.8% were obese or did not control body weight within the past 1 year. Of all NAFLD patients, 50.5% were complicated by hyperlipidemia, 18.5% were complicated by diabetes, and 29.5% were complicated by hypertension; 43.0% had not received standardized treatment, and among the other 57.0% respondents who received treatment, 79.0% were given non-drug treatment such as reasonable diet and physical exercise. In NAFLD patients who were not improved after treatment, the major cause of failure was that they were not able to stick to healthy living habits. Most NAFLD patients were willing to obtain the knowledge of disease through television, website, and newspaper.@*Conclusion@#Medical staff do not have enough awareness of NAFLD, and some of them cannot perform standardized diagnosis and treatment of NAFLD with reference to clinical guidelines. Therefore, the education on NAFLD should be enhanced for medical staff to guide them to perform accurate screening, diagnosis, evaluation, and treatment of NAFLD. The general population has low awareness of NAFLD and NAFLD patients have poor treatment compliance, which are important causes of increased incidence rate of NAFLD and disease progression. The general population should be educated about NAFLD to help them establish a reasonable lifestyle.
ABSTRACT
Objective To investigate the differences of expression and activation of natural killer (NK) cell G2D (NKG2D) in patients with different immune status of chronic hepatitis B virus (HBV) infection, and to explore the significance of NKG2D-mediated immune injury in HBV infection.Methods Fifteen chronic HBV carriers (immune tolerance),15 chronic hepatitis B (CHB, immune activation) patients, 15 HBV-related acute/subacute-on-chronic liver failure (HBV-ACLF, immune over-activation) patients were enro1led in this study from January 2010 to December 2011 in the Third Hospital of Hebei Medical University.The frequencies of NK cells and NKG2D+ NK cells in peripheral blood mononuclear cells (PBMC) were detected by flow cytometry.The NKG2D mRNA expressions were measured by real-time fluorescent quantitative polymerase chain reaction.Localization and hemi-quantitative analysis of NKG2D+ cells in liver tissue were performed by immunohistochemistry staining.Concentrations of serum interferon(IFN)-γ, tumor necrosis factor(TNF)-α, perforin and granzyme B were quantified by enzyme 1inked immunosorbent assay (ELISA).Normally distributed continuous variables were analyzed using one-way analysis of variance (ANOVA), followed by Student-Newman-Keuls q test for evaluating variances between each two groups.For non-normally distributed data or heterogeneity of variance, differences between groups were analyzed using nonparametric Kruskal-Wallis H test, followed by Nemenyi test for pairwise comparisons.Pearson chi-square test was used to analyze categorical variables.Results The percentages of NK cells in PBMC were (13.58±3.24)% in healthy controls, (5.42±2.18)% in chronic HBV carriers, (7.92±2.85)% in HBV-ACLF group and (8.43±2.92)% in CHB group.The percentage of NK cells in PBMCs was lower in each chronic HBV-infected group compared with healthy controls (F=22.04, P<0.05).The frequency of NKG2D+ NK cells in HBV-ACLF group (18.92±5.85)% was the highest, followed by CHB group (12.85±3.39)%, healthy controls (8.45±2.86)%, and chronic HBV carriers (3.36±1.05%), with the statistically significant differences between each two groups (H=46.09, P<0.01).Intrahepatic NKG2D mRNA expression and NKG2D+ cells density were highest in HBV-ACLF group (6.58±1.86 and 30.69±6.67, respectively), followed by CHB group (3.25±0.95 and 17.36±4.13, respectively) and chronic HBV carriers (0.69±0.20 and 3.16±1.24, respectively), with the statistically significant differences between each two groups (H=52.10 and 52.73 respectively, both P<0.01).The similar patterns were observed in serum IFN-γ, TNF-α, perforin and granzyme B concentrations.Conclusions NKG2D expresses variously in patients with different immune status of chronic HBV infection.Activation of NKG2D may take part in the immune pathogenesis of chronic HBV infection.