Over the past three decades， China has made significant progress in the prevention and control of viral hepatitis， and the incidence rates of new-onset pediatric hepatitis B virus infections and acute viral hepatitis in the population have reduced to a relatively low level； however， there is still a heavy disease burden of chronic viral hepatitis in China， which severely affects the health status of the population. This study systematically summarizes the achievements of viral hepatitis prevention and control in China， analyzes existing problems and challenges， and proposes comprehensive prevention and control strategies and measures to eliminate viral hepatitis as a public health threat based on the national conditions of China， in order to provide a reference for related departments in China on how to achieve the action targets for eliminating viral hepatitis as a public health threat by 2030.

Objective To evaluate the safety and efficacy of transcatheter arterial chemoembolization(TACE)combined with lenvatinib and camrelizumab in the treatment of advanced hepatocellular carcinoma(HCC).Methods The clinical data of a total of 63 patients with advanced HCC,who received TACE combined with lenvatinib and camrelizumab(triple therapy)or TACE combined with lenvatinib(dual therapy)at the Jingmen Municipal People's Hospital of China between April 2020 and December 2021,were retrospectively analyzed.Triple therapy group had 30 patients,and dual therapy group had 33 patients.The post-treatment tumor response,disease progression-free survival(PFS),overall survival(OS),and the incidence of adverse drug reactions were recorded.Results The median follow-up period of the two groups was 14 months(range of 4-26 months).Compared with the dual therapy group,in the triple therapy group the objective response rate(ORR)was remarkably higher(83.3%vs.57.6%,P=0.026),the disease control rate(DCR)was obviously higher(93.3%vs.69.7%,P=0.039),the median PFS was significantly longer(8.0 months vs.5.0 months,P＜0.01),and the median OS was strikingly longer(24.0 months vs.12.0 months,P=0.004).No statistically significant difference in the incidence of adverse drug reactions existed between the two groups(P＞0.05).Conclusion For the treatment of advanced HCC,TACE combined with lenvatinib and camrelizumab is clinically safe and effective.(J Intervent Radiol,2024,32:57-62)

Objective:This study aims to compare the antiviral treatment similarities and differences in the population covered by the 2024 version of the World Health Organization's (WHO) hepatitis B prevention and treatment guidelines and the current Chinese hepatitis B prevention and treatment guidelines, so as to explore their impact on the indications for antiviral therapy in Chinese patients with chronic hepatitis B (CHB).Methods:The information of patients with chronic hepatitis B virus infection who did not receive antiviral treatment was collected through the registration database of the China Clinical Research Platform for Hepatitis B Elimination. Descriptive statistics were conducted on the demographic, blood, biochemical, and virological levels of patients according to the treatment recommendations of the two versions of the guidelines. The Mann-Whitney U test and χ2 test were used to compare the differences and proportional distribution of the treatment populations covered by the two guidelines. The χ2 test was used to analyze the coverage rate of different antiviral treatment indications.Results:A total of 21,134 CHB patients without antiviral treatment were enrolled. 69.4% of patients met the 2024 versions of the WHO guidelines' recommendations. 85.0% of patients met the current Chinese hepatitis B prevention and treatment guidelines. The WHO guidelines for antiviral therapy indications were met in younger patients with higher levels of ALT, AST, and APRI scores, as well as greater proportion of patients with higher viral loads (P<0.001). The WHO guidelines recommended a cut-off value of APRI>0.5, which raised the proportion of patients on antiviral therapy from 6.6% to 30.9%. 45.7% of patients met the antiviral indications for HBV DNA >2000 IU/ml with abnormal transaminase (ALT>30 U/L for males and ALT>19 U/L for females). The reduced APRI diagnostic cut-off value and ALT treatment threshold had further increased the treatment coverage rate by 91.6% in patients with chronic HBV infection in line with the 2024 versions of WHO guidelines.Conclusion:The reduction of the APRI diagnostic cut-off value and the ALT treatment threshold, based on the current hepatitis B guidelines of China, will further improve the treatment coverage of CHB patients.

Background/Aims: Existing hepatocellular carcinoma (HCC) prediction models are derived mainly from pretreatment or early on-treatment parameters. We reassessed the dynamic changes in the performance of 17 HCC models in patients with chronic hepatitis B (CHB) during long-term antiviral therapy (AVT). Methods: Among 987 CHB patients administered long-term entecavir therapy, 660 patients had 8 years of follow-up data. Model scores were calculated using on-treatment values at 2.5, 3, 3.5, 4, 4.5, and 5 years of AVT to predict threeyear HCC occurrence. Model performance was assessed with the area under the receiver operating curve (AUROC). The original model cutoffs to distinguish different levels of HCC risk were evaluated by the log-rank test. Results: The AUROCs of the 17 HCC models varied from 0.51 to 0.78 when using on-treatment scores from years 2.5 to 5. Models with a cirrhosis variable showed numerically higher AUROCs (pooled at 0.65–0.73 for treated, untreated, or mixed treatment models) than models without (treated or mixed models: 0.61–0.68; untreated models: 0.51–0.59). Stratification into low, intermediate, and high-risk levels using the original cutoff values could no longer reflect the true HCC incidence using scores after 3.5 years of AVT for models without cirrhosis and after 4 years of AVT for models with cirrhosis. Conclusions The performance of existing HCC prediction models, especially models without the cirrhosis variable, decreased in CHB patients on long-term AVT. The optimization of existing models or the development of novel models for better HCC prediction during long-term AVT is warranted.

Objective:To analyze risk factors for prognosis of adult patients with traumatic brain injury (TBI), construct the prognostic model of TBI and evaluate its predictive value.Methods:A case-control study was used to analyze the clinical data of 522 patients with TBI admitted to Xijing Hospital of Air Force Medical University from March 2011 to September 2019, including 438 males and 84 females; aged 18-75 years [(44.9±15.0)years]. According to the Glasgow outcome score (GOS) at discharge, the patients were divided into good prognosis group (GOS 4-5 points, n=165) and poor prognosis group (GOS 1-3 points, n=357). The two groups were compared with regards to qualitative data such as sex, underlying diseases, causes of injury, multiple injuries, open injuries, intracranial foreign bodies, cerebral herniation, consciousness status on admission and at discharge, surgery, lung infection on admission, tracheostomy, ventilator-assisted ventilation, hospital-acquired pneumonia/pathogenic bacteria and intracranial infection, and quantitative data such as Glasgow coma score (GCS) on admission and at discharge, age, measurements on admission [systolic blood pressure, diastolic blood pressure, mean arterial pressure, temperature, heart rate, creatinine, urea nitrogen, blood sodium, blood potassium, blood glucose, prothrombin time (PT), activated partial thromboplastin time (APTT), platelets, international normalized ratio (INR), pupil size of both eyes] and length of hospital stay. Univariate analysis and Lasso regression analysis were used to screen the risk factors affecting the prognosis of TBI patients, and the selected influencing factors were included in multivariate Logistic regression analysis to identify independent risk factors and construct regression equations. R was used to draw a visual nomogram based on regression equation for predicting the prognosis of TBI patients. The prognostic predictive value of the nomogram was evaluated by using the receiver operating characteristic (ROC) curve, and the area under the curve (AUC), Youden index, sensitivity, specificity and consistency index (C index) were calculated. Results:Univariate analysis showed that there were significant differences between the two groups in underlying diseases, open injuries, cerebral herniation, consciousness status on admission and at discharge, lung infection on admission, tracheostomy, ventilator-assisted ventilation, hospital-acquired pneumonia/pathogenic bacteria, GCS on admission and at discharge, age, and measurements on admission (systolic blood pressure, mean arterial pressure, body temperature, heart rate, creatinine, urea nitrogen, blood potassium, blood glucose, PT, INR, pupil size of right eye) (all P<0.05 or 0.01). There were no significant differences between the two groups in gender, causes of injury, multiple injuries, intracranial foreign bodies, surgery, intracranial infection, measurements on admission (diastolic blood pressure, blood sodium, APTT, platelets, pupil size of left eye) and length of hospital stay (all P>0.05). After screening by Lasso regression model, the results of multivariate Logistic regression analysis showed that GCS on admission ( OR=0.67, 95% CI 0.62, 0.73, P<0.01), age ( OR=1.03, 95% CI 1.01, 1.04, P<0.01), blood glucose on admission ( OR=1.17, 95% CI 1.06, 1.30, P<0.01) and INR on admission ( OR=17.08, 95% CI 2.12, 137.89, P<0.01) could be used as the main risk factors to construct the prediction model, and the regression equation was constructed: Logit [ P/(1- P)]=-0.398× "GCS on admission"+0.024× "age"+0.158×"blood glucose on admission"+2.838×"INR on admission"-1.693. The AUC for the prognosis prediction in adult patients with TBI using R based on a visual nomogram model was 0.87 (95% CI 0.83, 0.89, P<0.01). The Youden index for the predicted probability was 0.60 (sensitivity of 85.2% and specificity of 75.2%), with the C index of 0.87. Conclusion:Age, GCS on admission, blood glucose on admission and INR on admission are the main risk factors affecting the prognosis of TBI in adults, and the nomogram drawn by these parameters can better predict their clinical outcome.

Objective To describe the characteristics and registration status of clinical trials of new drugs for nonalcoholic steatohepatitis (NASH), and to provide a reference for the design and implementation of clinical trials of new drugs for NASH. Methods The U.S. Clinical Trials Database, China Clinical Trial Registry, and Center for Drug Evaluation, National Medical Products Administration, were searched for clinical trials of new drug registration and interventional studies with NASH as the indication published up to August 6, 2021, using NASH in English and Chinese characters as the keywords, and liver cirrhosis was excluded. Two researchers independently searched and screened the articles to extract relevant information. Results A total of 196 clinical trials of new drug registration or interventional studies for NASH were included, among which there were 174 trials registered abroad and 22 trials registered in China, and the number of registrations tended to increase year by year. The numbers of phase Ⅰ, phase Ⅰ/Ⅱ(including Ⅰb/Ⅱa), phase Ⅱ, phase Ⅱ/Ⅲ, and phase Ⅲ clinical trials were 45(23.0%), 8(4.1%), 112(57.1%), 4(2.0%), and 19(9.7%), respectively. The main drug types included farnesoid X receptors, fibroblast growth factors, peroxisome proliferator-activated receptor agonists, and glucagon-like peptide-1, with numbers of 16(8.16%), 14(7.14%), 11(5.61%), and 13(6.63%), respectively. The clinical trials of innovative drugs for NASH initiated by the sponsors in European and American regions accounted for the highest proportion, and there was a gradual increase in the number of clinical trials of innovative drugs in China in recent years, with a similar distribution of single-center and multicenter clinical trials. As for the trials with NASH patients as subjects, the numbers of trials with pathology, imaging, and clinical diagnosis as the main inclusion criteria were 125, 66, and 42, respectively. Phase Ⅰ clinical trials used safety, tolerability, and pharmacokinetic parameters as the main assessment indices, while phase Ⅱ and phase Ⅲ clinical trials often used safety and efficacy as the main assessment indices. The number of clinical trials for the registration of innovative drugs for NASH was relatively low but kept increasing in China, and there were fewer clinical trials of innovative traditional Chinese medicine drugs compared with innovative chemical drugs. Conclusion There is a significant increase in the registration of international clinical trials of innovative drugs for NASH, and most of these trials are in the early phases, with large differences in inclusion criteria and assessment indices, a lack of unified evaluation indices, and relatively few trials with new designs. There are fewer clinical trials of innovative drugs for NASH in China than in European and American countries, and the number of such trials is gradually increasing in China.

Objective:To investigate the influence and mechanism of micro RNA (miR)-373-3p in autophagy and sunitinib sensitivity of glioblastoma cells.Methods:U251 cells were routinely cultured in vitro; and some U251 cells were subjected to 50 μmol/L sunitinib treatment for 72 h to construct sunitinib-resistant U251 cell line. (1) Real-time reverse transcription quantitative PCR (RT-qPCR) was used to detect the miR-373-3p expression in U251 and sunitinib-resistant U251 cells. Sunitinib-resistant U251 cells were divided into blank control group, nonsense sequence group and miR-373-3p mimic group; cells in the latter 2 groups were transfected with nonsense sequence and miRNA-337-3p mimic, respectively; miR-373-3p expression was detected by RT-qPCR. Cells were divided into U251 group, sunitinib-resistant U251 group, sunitinib-resistant U251+nonsense sequence group, and sunitinib-resistant U251+miR-373-3p mimic group; after each transfection, CCK-8 assay was used to evaluate the cell viability; TUNEL was used to detect the apoptotic rate; immunofluorescent assay was used to detect the expression of microtubule-associated protein light chain 3 (LC3); Western blotting was used to detect the expressions of apoptosis- and autophagy-associated proteins. (2) The pGL3-autophagy-related gene 7 (ATG7) wild-type (WT) and pGL3-ATG7 mutant type (MUT) plasmids were established; dual-luciferase reporter system was used to detect the cell luciferase activity in the miR-373-3p mimic group and nonsense sequence group. Cells were divided into U251 group, sunitinib-resistant U251 group, sunitinib-resistant U251+nonsense sequence group, and sunitinib-resistant U251+miR-373-3p mimic group; after each transfection, RT-qPCR and Western blotting were used to detect the mRNA and protein expressions of ATG7 in the cells. (3) The sunitinib-resistant U251 cells were divided into blank control group, ATG7 negative control group, and ATG7 overexpression group; after each transfection, RT-qPCR and Western blotting were used to detect the ATG7 mRNA and protein expressions. U251 and sunitinib-resistant U251 cells were divided into U251 group, sunitinib-resistant U251 group, sunitinib-resistant U251+nonsense sequence group, sunitinib-resistant U251+miR-373-3p mimic group, sunitinib-resistant U251+miR-373-3p mimic+ATG7 negative control group, and sunitinib-resistant U251+miR-373-3p mimic+ATG7 overexpression group; after each transfection, CCK-8 assay was used to evaluate the cell apoptosis, TUNEL was used to examine the apoptotic rate, and Western blotting was employed to detect the expressions of apoptosis- and autophagy-associated proteins. Results:(1) As compared with that in the U251 cells, miR-373-3p was lowly expressed in sunitinib-resistant U251 cells, with statistic difference ( P<0.05). As compared with that in the blank control group and nonsense sequence group, miR-373-3p expression was significantly elevated in the miR-373-3p mimic group ( P<0.05). As compared with the U251 group, the sunitinib-resistant U251 group had significantly increased cell viability, significantly decreased cell apoptotic rate, statistically increased B lymphocytoma-2 (Bcl-2) and Beclin 1 protein expressions, and significantly increased LC3II/LC3I values, significantly decreased Bcl-2 associated X protein (Bax) and p62 protein expressions and cleaved Caspase3/Caspase 3 values ( P<0.05). As compared with the sunitinib-resistant U251+nonsense sequence group, the sunitinib-resistant U251+miR-373-3p mimic group had significantly decreased cell viability, significantly increased cell apoptotic rate, statistically decreased Bcl-2 and Beclin 1 protein expressions, and significantly decreased LC3II/LC3I values, significantly increased Bax and p62 protein expressions and cleaved Caspase3/Caspase 3 values ( P<0.05). As compared with the U251 group, the sunitinib-resistant U251 group had increased number of fluorescent particles labeled with LC3 and enhanced fluorescent intensity; as compared with the sunitinib-resistant U251+nonsense sequence group, the sunitinib-resistant U251+miR-373-3p mimic group had decreased number of fluorescent particles labeled with LC3 and reduced fluorescent intensity. (2) The luciferase activity of pGL3-ATG7 WT plasmids in the miR-373-3p mimic group was signficantly lower than that in nonsense sequence group ( P<0.05). As compared with those in the U251 group, ATG7 mRNA and protein expressions were both significantly increased in the sunitinib-resistant U251 group ( P<0.05); as compared with those in the sunitinib-resistant U251+nonsense sequence group, ATG7 mRNA and protein expressions were both significantly decreased in the sunitinib-resistant U251+miR-373-3p mimic group ( P<0.05). (3) As compared with the blank control group and ATG7 negative control group, the ATG7 overexpression group had significantly increased ATG7 mRNA and protein expressions ( P<0.05). As compared with the sunitinib-resistant U251+nonsense sequence group, the sunitinib-resistant U251+miR-373-3p mimic group had significantly decreased cell viability, significantly increased cell apoptotic rate, statistically decreased Bcl-2 and Beclin 1 protein expressions, significantly decreased LC3II/LC3I values, significantly increased Bax and p62 protein expressions, and significantly increased cleaved Caspase3/Caspase 3 values ( P<0.05). As compared with the sunitinib-resistant U251+miR-373-3p mimic+ATG7 negative control group, the sunitinib-resistant U251+miR-373-3p mimic+ATG7 overexpression group had significantly increased cell viability, significantly decreased apoptotic rate, statistically increased Bcl-2 and Beclin 1 protein expressions, significantly increased LC3II/LC3I values, significantly decreased Bax and p62 protein expressions, and significantly decreased cleaved Caspase3/Caspase 3 values ( P<0.05) Conclusion:MiR-373-3p can enhance sunitinib sensitivity by regulating autophagy in glioblastoma cells, whose mechanism might be related to targeting ATG7.

Objective:Our study aims to determine histological regression and clinical improvement after long-term antiviral therapy in hepatitis B virus-related cirrhosis patients.Methods:Treatment-na?ve chronic hepatitis B patients with histologically or clinically diagnosed liver cirrhosis were enrolled. Liver biopsies were performed after 5 years entecavir-based antiviral treatment. Patients were followed up every 6 months. Cirrhosis regression was evaluated based on Metavir system and P-I-R score. Clinical improvement was evaluated before and after the long-term treatment. Kruskal Wallis test and Wilcoxon signed-rank test were used for continuous variables, Fisher's exact test was used for categorical variables and multivariate analysis was performed using logistic regression analysis.Results:Totals of 73 patients with HBV-related liver cirrhosis were enrolled. Among them, 30 (41.1%) patients were biopsy proved liver cirrhosis and the remaining 43 (58.9%) cirrhotic patients were diagnosed by clinical features. Based on Metavir system and P-I-R score, 72.6% (53/73) patients attained histological regression. Furthermore, 30.1% (22/73) were defined as significant regression (Metavir decrease ≥2 stage), 42.5% (31/73) were mild regression (Metavir decrease 1 stage or predominantly regressive by P-I-R system if still cirrhosis after treatment) and 27.4% (20/73) were the non-regression. Compared to levels of clinical characteristics at baseline, HBV DNA, ALT, AST, liver stiffness(decreased from 12.7 to 6.4 kPa in significant regression, from 18.1 to 7.3 kPa in mild regression and from 21.4 to 11.2 kPa in non-regression)and Ishak-HAI score significantly decreased after 5 years of anti-HBV treatment, while serum levels of platelets and albumin improved remarkably ( P<0.05). In multivariate analysis, only the pre-treatment liver stiffness level was associated with significant regression ( OR=0.887, 95% CI: 0.802-0.981, P=0.020). Conclusions:After long-term antiviral therapy, patients with HBV-related cirrhosis are easily to attain improvements in clinical parameters, while a certain percentage of these patients still cannot achieve histological reversal.

Objective:To clarify the effect and related factors of antiviral therapy on the change of esophageal varices in patients with hepatitis B virus-related cirrhosis.Methods:Fifty-two cases with hepatitis B virus-related cirrhosis who underwent endoscopy before and after antiviral therapy were selected from prospective cohorts. Patients were divided into three groups: no, mild, and moderate-severe based on the degree of esophageal varices. The changes in the severity of esophageal varices in each group were compared after antiviral therapy. Clinical characteristics (platelet, liver and kidney function, liver stiffness, and virological response) of patients with different regressions were analyzed. Measurement data were analyzed by independent sample t-test, one-way ANOVA, Mann-Whitney U test and Kruskal-Wallis H test, and Chi-Square test was used for count data.Results:All patients received entecavir-based antiviral therapy. The median treatment time was 3.1 (2.5-4.4) years. The proportion of patients without esophageal varices increased from 30.8% to 51.9%, the proportion of mild esophageal varices decreased from 40.4% to 30.8%, and the proportion of patients with moderate-to-severe esophageal varices decreased from 28.8% to 17.3% ( χ2=14.067, P=0.001). A total of 40.4% of patients had esophageal varices regression, and 13.5% had esophageal varices progression. The progression rate was significantly higher in patients with moderate-severe esophageal varices than patients with mild and no esophageal varices ( χ2=28.126, P<0.001), and 60.0% of patients with moderate-severe esophageal varices still remained in moderate-severe state after antiviral treatment. Baseline platelet count and 5-year mean change rates were significantly lower in patients with progressive moderate-to-severe esophageal varices than in those without progression (+3.3% vs. +34.1%, Z=7.00, P=0.027). Conclusion:After effective antiviral treatment, 40.4% of patients with hepatitis B virus-related cirrhosis combined with esophageal varices has obtained esophageal varices regression, but those with moderate to severe esophageal varices still have a considerable risk of progression while receiving mono antiviral treatment only. Thrombocytopenia and without significant improving are the clinical signs of progression risk after receiving antiviral treatment.

Objective:To comparatively study the similarities and differences between the clinical, pathological, and risk factors of advanced fibrosis in men and women with non-alcoholic fatty liver disease (NAFLD).Methods:267 patients with NAFLD diagnosed by liver biopsy were retrospectively included, and were divided into male and female groups. The difference of clinical and pathological indexes were compared between the two groups. The measurement data were in accordance with normal distribution. The comparison between the two groups was performed by independent sample t-test. The non-parametric test was used for non-normal distribution. The classification data were expressed as a percentage, and the chi-square test was used for comparison between groups. Logistic regression analysis was used to analyze the risk factors.Results:The age of onset of NAFLD was significantly lower in male than female patients ( P < 0.01). There was no statistically significant difference between the male and female groups in terms of body mass index and the prevalence of type 2 diabetes ( P > 0.05). Biochemical index: The levels of alanine aminotransferase, albumin, total bilirubin and uric acid were significantly higher in male than female patients ( P < 0.01). Liver pathology: The proportion of ballooning degeneration was significantly lower in male than female patients ( P < 0.01). There was not statistically significant difference between the two groups in the proportion of steatohepatitis score, non-alcoholic steatohepatitis (52.0% vs. 61.5%, P = 0.283) and advanced liver fibrosis (14.3% vs. 17.8%, P = 0.162). Thrombocytopenia was a common independent risk factor for advanced stage liver fibrosis ( OR = 0.984, 0.978~0.989, P < 0.01). Type 2 diabetes was only an independent risk factor for advanced stage liver fibrosis in men ( OR = 6.557, 1.667~25.782), P < 0.01). Elevated AST was only an independent risk factor for advanced stage liver fibrosis in women ( OR = 1.016, 1.003~1.028, P = 0.012). Conclusion:In NAFLD patients, there are some clinical and pathological differences between genders. Platelets are a common predictor of advanced liver fibrosis in men and women. Type 2 diabetes in men and elevated aspartate aminotransferase in women can be regarded as independent risk factors for advanced liver fibrosis.