Hepatitis B is a major global public health issue. Through the implementation of comprehensive prevention and control strategies centered on hepatitis B vaccination， China has achieved remarkable progress in hepatitis B prevention and control， while there are still many issues and challenges. This article reviews the development of hepatitis B vaccination strategies in China， analyzes the goal and advances in vaccination in different populations， and problems and challenges， in order to provide a reference for further optimizing vaccination strategies and improving the levels of prevention and control.

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 analyze epidemiological characteristics and spatiotemporal clustering of hepatitis A in China from 2005 to 2023.Methods:The incidence data of hepatitis A in China during 2005-2023 were collected from the China Disease Control and Prevention Information System .Results:From 2005 to 2023, a total of 605 509 cases of hepatitis A were reported in China. The average annual reported incidence rate was 2.32/100 000, the incidence was 2.85/100 000 in men and 1.81/100 000 in women, and the incidence was 3.25/100 000 in age group 0-14 years, 2.10/100 000 in age group 15-64 years and 2.49/100 000 in age group ≥65 years , respectively. The case count in farmers was highest (40.57%, 245 639/605 509). The proportion of the cases in jobless or the unemployed increased most obviously (347.32%), and the proportion of the cases in students decreased most significantly (90.27%). The average annual reported incidence rate in the western China was highest (4.45/100 000), followed by that in northeastern China (2.02/100 000), central China (1.89/100 000) and eastern China (1.16/100 000). From 2020 to 2023, the incidence of hepatitis A showed no spatial clustering. From 2005 to 2019, the obvious hot spots and high-high clustering areas mainly distributed in provinces, such as, Sichuan, Qinghai, Xinjiang, Xizang and Gansu. The low-low clustering areas were mainly distributed in Beijing, Tianjin, Hebei, Shandong, Jiangsu, Shanghai, Zhejiang, Fujian, Henan, Anhui, Jiangxi, Jilin and Liaoning. An independent high-low clustering was found in Shanxi during 2014-2019. A total of 5 high incidence clustering areas were detected through spatiotemporal scanning analysis.Conclusions:The incidence rate of hepatitis A in China declined significantly from 2005 to 2023. The reported incidence rate in the elderly showed no obvious decrease, and the reported cases accounted for the highest proportion in the whole population. Before 2020, the reported incidence rate of hepatitis A showed high-high clustering in western China, the spatiotemporal clustering disappeared from 2020 to 2023, but the reported incidence rate of hepatitis A in western China was still high. It is suggested to pay attention to the prevention and control of hepatitis A in populations at high risk and areas with high incidence of hepatitis A.

Objective:To analyze the whole genome sequence and key site mutations of hepatitis B virus (HBV) in patients with different stages of disease progression, and to understand the relationship between HBV genetic characteristics and disease progression.Methods:Serum samples and basic information of hepatitis B patients with asymptomatic HBV carrier, chronic hepatitis B patients, cirrhosis patients and primary hepatocellular carcinoma patients were collected. Nested PCR was used to amplify the samples to obtain HBV whole gene sequences. Phylogenetic trees were constructed to determine the genotype of the samples, and gene mutations of the samples were analyzed combined with reference sequences of each type.Results:A total of 256 samples were successfully amplified, including 68 asymptomatic HBV carrier patients, 118 CHB patients, 15 LC patients and 55 HCC patients, and five genotypes (B, C, D, I and C/D) were detected. The result of comparative analysis showed that the mutation rate of 56 nucleotide sites was significantly different among the four groups ( P<0.05). In addition to the discovery of C105T, A1762T/G1764A and G1899A and other previously reported key site mutations, the mutation rates of T53A, C1485T and C1628T in newly diagnosed HCC group were significantly higher than those in other groups, and the mutation rates of T2150G and T2151C in asymptomatic HBV infection group were significantly higher than those in other groups. A total of 26 sequences were deleted, mainly distributed in the pre-C and pre-S regions. The deletion mutation rate in the HCC group was significantly higher than that in the other groups. Conclusions:The data of this study indicate that some nucleotide substitution mutations and deletion mutations may be closely related to the occurrence and development of HBV-related diseases, and HCC patients are more likely to have gene mutations than non-HCC patients. These result provide a reference for understanding the relationship between viral mutation and the progression of HBV infection-related diseases.

Objective:To summarize the use of Castor stent graft in aortic diseases and to analyze their efficacy.Methods:The clinical data of patients with aortic diseases treated with Castor stent graft from November 2017 to August 2022 in Fujian Provincial Hospital were collected and divided into branched stent group and branched stent co-operative group according to the operation method, and the clinical data of both groups were summarized.Results:A total of 75 cases of aortic disease were treated with Castor stents, and finally 53 cases were classified as branched stent group and 22 cases as branched stent co-operative group. The operations in both groups were successful. The median operative time in the branched stent group was 120(100, 160)min, and the median postoperative hospital stay was 7.0(5.5, 10.5)days.There was no postoperative ischemic stroke, no spinal cord ischemia. One case of new aortic dissection occurred. During follow-up, there was one lost case and two deaths, and the rest did not have endoleak, branch stent stenosis, ischemic stroke or re-intervention. In the branched stent co-operative group, there was one postoperative ischemic stroke, one case of slight stenosis of the left subclavian artery stent during follow-up, the remaining cases had satisfactory postoperative outcomes.Conclusion:Castor stent graft is a safe and effective procedure in the treatment of aortic diseases. And Castor stent graft can be used in combination with other endovascular repair techniques in the treatment of complex aortic diseases, with safe and reliable postoperative outcomes.

Objective:To evaluate the effect of niraparib, the poly (ADP-ribose) polymerase (PARP) inhibitor, on the radiosensitivity of esophageal squamous cell carcinoma (ESCC) and to preliminarily investigate its mechanism.Methods:Human esophageal squamous cell carcinoma cells ECA-109 and KYSE-150 were divided into the control, niraparib, single irradiation, combined (niraparib+irradiation) groups. Cell proliferation was measured by CCK-8 assay. The changes of cell survival rate were detected by colony formation assay. The changes of cell cycle and apoptosis were analyzed by flow cytometry. The number of γH2AX foci was detected by immunofluorescence, and the expression levels of PARP-1, cleaved-PARP, RAD51, mitogen-activated protein kinase (MAPK) [extracellular signal-regulated kinase 1 and 2 (ERK1/2) ] and p-MAPK (ERK1/2) proteins were determined by Western blot. All data were expressed as Mean±SD. Data between two groups conforming to normal distribution through the normality test were subject to independent sample t-test and multiple groups were analyzed using one-way ANOVA. Results:In human ESCC cells ECA-109 and KYSE-150, the proliferation of ESCC cells was significantly inhibited by niraparib combined with irradiation, and the values of average lethal dose (D 0), quasi-threshould dose(D q), survival fraction after 2 Gy irradiation (SF 2) in the combined group were decreased compared with those in the single irradiation group. The effect of irradiation alone on apoptosis of ECA-109 and KYSE-150 cells was limited. Compared to single irradiation group, irradiation combined with niraparib further increased the apoptosis rate in ESCC cells ( P=0.015, P=0.006). In ECA-109 cells, G 2/M phase arrest was significantly increased in combined group compared with irradiation alone group ( P<0.001). In ECA-109 cells, the number of γH2AX foci in combined group was higher than that in the single irradiation group after 2 h, and showed a significantly slower decay of γH2AX foci ( P<0.001). Moreover, niraparib combined with irradiation enhanced the radiation-induced cleavage of PARP-1 and down-regulated the expression of Rad51 and p-MAPK(ERK1/2). Conclusion:Niraparib can increase the radiosensitivity of esophageal cancer cells by inhibiting cell proliferation, promoting cell apoptosis, inhibiting the repair of DNA damage and regulating the MARK-ERK signaling pathway.

Objective:To investigate the diagnostic value of peripheral blood systemic immune inflammatory in-dex(SII)in histological chorioamnionitis(HCA)and the predictive value of adverse pregnancy outcomes.Meth-ods:A total of 138 pregnant women with suspected HCA were included from January 2021 to June 2022 in Peo-ple's Hospital of Zhengzhou as the research objects.According to the results of placental pathology examination,they were divided into non-HCA group(66 cases)and HCA group(72 cases).The general clinical data,laboratory indicators and adverse outcome indicators of the two groups were compared,and the relationship between the a-bove indicators and HCA was analyzed by multivariate Logistic regression.ROC curve was used to analyze the predictive value of SII for HCA and adverse pregnancy outcomes.Results:①Logistic regression analysis showed that increased neutrophil percentage(Neut％)and SII could increase the risk of HCA(OR＞1,P＜0.05),and in-creased lymphocyte percentage(Lym％)was beneficial for reducing the risk of HCA(OR＜1,P＜0.05).②ROC curve analysis showed that the area under the curve(AUC)of Neut％and Lym％for diagnosing HCA were 0.628 and 0.638,respectively,while the AUC of SII was higher(0.722),and the diagnostic threshold of SII was 974.49 ×109/L.③The rates of postpartum hemorrhage,neonatal infection and premature delivery in high SII group(SII＞974.49 ×103/L)were higher than those in low SII group(SII ≤974.49 ×109/L),and the difference was statistically significant(P＜0.05).The value of SII in predicting postpartum hemorrhage(AUC 0.708)and neonatal infection(AUC 0.848)were higher than that in preterm birth(AUC 0.637).Conclusions:Abnormal Neut％and Lym％levels increase the risk of HCA to some extent,but the diagnostic value of HCA is average.Peripheral blood SII has high diagnostic value in HCA,and has good predictive value for postpartum hemorrhage and neonatal infection,which is expected to be a new indicator for prenatal diagnosis and prognosis prediction of adverse pregnancy outcomes in HCA.

Objective:To analyze the genotype distribution of acute hepatitis B virus in China.Methods:A total of six hundred and twenty acute Hepatitis B cases reported to China Information System for Diseases Control and Prevention from 2015 to 2017 were selected. First, the full-length HBV genome was obtained by nested PCR amplification. In addition, the HBV genotype was determined by constructing a phylogeny tree. Finally, using primarydata, HBV genotype distribution was analyzed.Results:A total of 519 (83.71%, 519/620) sequences were obtained genotype of 620 acute hepatitis B cases, including A (0.19%, 1/519), B (27.17%, 141/519), C (62.04%, 322/519), D (9.06%, 47/519), I (0.77%, 4/519) and C/D (0.77%, 4/519); B2(95.03%, 134/141) and C2 (72.67%, 234/322) were the two major subgenotypes. Genotypes were distributed differently in seven regions of China. The proportion of genotype C appeared higher in Northeast China (94.55%, 52/55), North China (93.85%, 61/65), East China (78.87%, 56/71), and South China (58.14%, 50/86). The proportion of genotype B was higher in Central China (58.07%, 36/62) and Southwest China (52.94%, 45/85), the proportion of genotype D was the highest in Northwest China (48.42%, 46/95). A total of 515 cases were classified as serotypes, including 'adr' (57.48%, 296/515), 'adw' (30.87%, 159/515), 'ayr' (0.19%, 1/515), and 'ayw' (11.46%, 59/515). Genotype B was dominated by 'adw' serotype (92.14%, 129/140), genotype C was dominated by 'adr' serotype (91.88%, 294/320),all genotype D were 'ayw' serotype. The genotype of acute hepatitis B was correlated with serotype, 'adw' was dominant in genotype B, 'adr' was dominant in genotype C and 'ayw' was dominant in genotype D.In different gender and age group, there was no statistical significance ingenotype distribution ( P>0.05). Conclusions:The genotype of acute hepatitis B in China from 2015 to 2017 was mainly B, C, and D; genotype C was dominant in the Northeast China,North China, East China and South China; B and C were common in Central and Southwest China, and genotype B was dominant. Genotype D was primarily distributed in Northwest China. The genotype of acute hepatitis B was correlated with serotype, 'adw' was dominant in genotype B, 'adr' was dominant in genotype C and 'ayw' was dominant in genotype D. There was no difference in the distribution of acute hepatitis B genotypes among different genders and age groups.

Objective:Assess the 10-year Immune persistence and the predictors after primary vaccination hepatitis B vaccine (HepB) among normal and high-responder infants.Methods:A total of 1 838 Infants of 7-12 months old located in Jinan, Weifang, Yantai and Weihai of Shandong Province who were induced normal or high antibody response (anti-HBs titer ≥ 100 mIU/ml) after primary vaccination (three dose with 0-1-6 procedure) with 5 μg recombinant HepB among newborns were included in the study, in 2009. 3 ml of venous blood samples were collected at baseline survey (T 0) and antibodies against hepatitis B surface antigen (anti-HBs), antibody against hepatitis B core antigen (anti-HBc) and hepatitis B surface antigen (HBsAg) were detected using chemiluminescence microparticle immunoassay (CMIA) method. A self-designed questionnaire was used to collect information including the infant′s age, sex, birth weight, premature birth, birth number, delivery location and mother′s HBV infection status. In 2014 (followed up for 5 years) and in 2019 (followed up for 10 years) (T 1), 2 ml of venous blood samples were collected. Anti HBS and anti HBC were detected by CMIA method. Those with anti HBS<10 mIU/ml were detected by CMIA method. Multivariate unconditional logistic and linear regression models were used to analyze the influencing factors of anti-HBs positive rate and geometric mean concentration (GMC) at T 1. Results:After 10 years follow-up, 73.94% of the subjects (1 359/1 835) finished the follow-up. 51.15% of the subjects, a total of 625 were boys. The positive rate of anti-HBs was 100% at T 0 and decreased to 53.44% (95% CI: 50.59%-56.26%) at T 1. The average annual decline rate of anti-HBs positive rate from T 0 to T 1 was 6.07%. The GMC of anti-HBs decreased from 607.89 (95% CI: 579.01-642.62) mIU/ml to 16.44 (95% CI: 15.06-18.00) mIU/ml. The average annual decline rate of anti-HBs GMC in 10-year follow-up was 30.30%. Multivariate logistic analysis showed that the positive rate of anti-HBs at T 1 was lower in those who did not vaccinate the first dose in time ( OR=0.25, 95% CI:0.07-0.71). Compared with those with GMC<1 000 mIU/ml at T 0, those with GMC ≥ 1 000 mIU/ml had a higher positive rate of anti-HBs at T 1 ( OR=2.29, 95% CI:1.76-2.97). Multivariate regression analysis showed that the GMC of anti-HBs at T 1 was lower in those who did not vaccinate the first dose in time (β=-0.50, 95% CI:-1.24-0.24). Compared with those with GMC<1 000 mIU/ml at T 0, those with GMC ≥ 1 000 mIU/ml had a higher GMC of anti-HBs at T 1 (β=0.81, 95% CI: 0.62-1.05). Conclusion:Anti-HBs GMC decreased in 10 years after primary vaccination of 5 μg recombinant hepatitis B vaccine among normal and high-responders. The anti-HBs persistence was mainly associated with whether the first dose was vaccinated in time and the level of anti-HBs at the end of primary vaccination.

Objective:Assess the 10-year Immune persistence and the predictors after primary vaccination hepatitis B vaccine (HepB) among normal and high-responder infants.Methods:A total of 1 838 Infants of 7-12 months old located in Jinan, Weifang, Yantai and Weihai of Shandong Province who were induced normal or high antibody response (anti-HBs titer ≥ 100 mIU/ml) after primary vaccination (three dose with 0-1-6 procedure) with 5 μg recombinant HepB among newborns were included in the study, in 2009. 3 ml of venous blood samples were collected at baseline survey (T 0) and antibodies against hepatitis B surface antigen (anti-HBs), antibody against hepatitis B core antigen (anti-HBc) and hepatitis B surface antigen (HBsAg) were detected using chemiluminescence microparticle immunoassay (CMIA) method. A self-designed questionnaire was used to collect information including the infant′s age, sex, birth weight, premature birth, birth number, delivery location and mother′s HBV infection status. In 2014 (followed up for 5 years) and in 2019 (followed up for 10 years) (T 1), 2 ml of venous blood samples were collected. Anti HBS and anti HBC were detected by CMIA method. Those with anti HBS<10 mIU/ml were detected by CMIA method. Multivariate unconditional logistic and linear regression models were used to analyze the influencing factors of anti-HBs positive rate and geometric mean concentration (GMC) at T 1. Results:After 10 years follow-up, 73.94% of the subjects (1 359/1 835) finished the follow-up. 51.15% of the subjects, a total of 625 were boys. The positive rate of anti-HBs was 100% at T 0 and decreased to 53.44% (95% CI: 50.59%-56.26%) at T 1. The average annual decline rate of anti-HBs positive rate from T 0 to T 1 was 6.07%. The GMC of anti-HBs decreased from 607.89 (95% CI: 579.01-642.62) mIU/ml to 16.44 (95% CI: 15.06-18.00) mIU/ml. The average annual decline rate of anti-HBs GMC in 10-year follow-up was 30.30%. Multivariate logistic analysis showed that the positive rate of anti-HBs at T 1 was lower in those who did not vaccinate the first dose in time ( OR=0.25, 95% CI:0.07-0.71). Compared with those with GMC<1 000 mIU/ml at T 0, those with GMC ≥ 1 000 mIU/ml had a higher positive rate of anti-HBs at T 1 ( OR=2.29, 95% CI:1.76-2.97). Multivariate regression analysis showed that the GMC of anti-HBs at T 1 was lower in those who did not vaccinate the first dose in time (β=-0.50, 95% CI:-1.24-0.24). Compared with those with GMC<1 000 mIU/ml at T 0, those with GMC ≥ 1 000 mIU/ml had a higher GMC of anti-HBs at T 1 (β=0.81, 95% CI: 0.62-1.05). Conclusion:Anti-HBs GMC decreased in 10 years after primary vaccination of 5 μg recombinant hepatitis B vaccine among normal and high-responders. The anti-HBs persistence was mainly associated with whether the first dose was vaccinated in time and the level of anti-HBs at the end of primary vaccination.