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Bletilla striata polysaccharide is a well-known antioxidant and immunomodulatory ingredient used in a variety of traditional Chinese medicine applications. A mouse aging model was constructed by intraperitoneal injection of D-galactose to explore the antioxidant and immunomodulatory effects of B. striata polysaccharides. B. striata polysaccharide was found to boost antioxidant capacity and retard aging in a subacutely aged mouse. In comparison to the cyclophosphamide alone group, the groups given 80 mg/kg and 160 mg/kg of B. striata polysaccharide showed considerably higher levels of total antioxidant capacity, superoxide dismutase, and catalase, with significantly lower malondialdehyde levels. To investigate the moderating effect of B. striata polysaccharide on immunological deficit, cyclophosphamide was injected into the abdominal cavity to create an immunocompromised mouse model. B. striata polysaccharide attenuated immunosuppressive effects of cyclophosphamide. The histological staining demonstrated that both liver and spleen cells in the control group were densely packed, with distinct nuclei and qualitative characteristics. The liver and spleen of the immunocompromised mice benefited significantly from 450 mg/kg B. striata polysaccharide. Taken together, B. striata polysaccharide exhibits an antioxidant and immunomodulatory effects in vivo. [ABSTRACT FROM AUTHOR]

The seamless phase Ⅱ/Ⅲ design integrates independent phase Ⅱ and phase Ⅲ clinical trials into a continuous, phased adaptive clinical trial design. Compared with traditional independent phase Ⅱ and phase Ⅲ clinical trials, the seamless design offers significant advantages in accelerating drug or vaccine development and improving clinical trial efficiency. Currently, the application of this design in anti-tumor drug research is becoming increasingly mature, and it is gradually expanding to clinical trials of vaccines, including the 9-valent human papillomavirus vaccine, sabin strain inactivated polio vaccine, and others. This paper aims to clarify the seamless phase Ⅱ/Ⅲ design concept and offer valuable insights into its implementation. It accomplishes this by presenting a clinical trial example featuring a phase Ⅱ/Ⅲ seamless design for a 9-valent human papillomavirus vaccine. The article delves into the specific considerations and potential challenges related to implementing the seamless design, aiming to provide valuable insights for optimizing vaccine clinical trials within our country.

Bridging study in vaccine clinical trials means a series of small-scale additional tests on the basis that the original safety and effectiveness of a vaccine have been confirmed in clinical trials, to prove that the characteristics of safety, immunogenicity and effectiveness of a vaccine are similar or consistent after component, population and immunization procedure change to other types which can extrapolate data from existing clinical trials. Compared with traditional vaccine clinical trials, bridging trials can promote the approval of vaccines to the market, accelerate the expansion of vaccine application, and promote the use of vaccines across regions and populations. In recent years, the application of bridge study design in vaccine clinical research has become more and more common. In order to better guide and promote the application of bridging trial design in the field of vaccine clinical research, we reviewed the design characteristics and application examples of bridging study design in vaccine clinical trials, and systematically elaborated the design ideas, key points and statistical evaluation methods of bridging study.

Between August and September, 2021, this study included 605 SARS-CoV-2 natural infection cases and 589 SARS-CoV-2 breakthrough cases from Nanjing and Yangzhou, as well as 690 inactivated COVID-19 vaccine recipients from Changzhou, China. In SARS-CoV-2 natural infection cases, the age range was 19-91 years (median age: 66 year), and the medians( Q 1 , Q 3 ) of IgG titers were 0.19 (0.06-1.31), 3.70 (0.76-69.48), 15.31 (2.59-82.16), 4.41 (0.99-31.74), 2.31 (0.75-13.83), 2.28 (0.68-9.94) and 2.80 (1.00-9.53) at one to seven weeks after SARS-CoV-2 infection, respectively. In SARS-CoV-2 breakthrough cases, the age range was 18-76 years (median age: 45 year), and the medians( Q 1 , Q 3 )of IgG titers were 1.93 (0.34-26.67), 38.87 (7.90-121.0), 75.09 (11.85-123.70), 21.97 (5.20-95.58), 13.97 (3.47-46.82), 9.56 (2.48-33.38) and 4.38 (1.87-11.00) at one to seven weeks after SARS-CoV-2 infection, respectively. In inactivated COVID-19 vaccine recipients, the age range was 18-87 years (median age: 47 years), and the medians( Q 1 , Q 3 )of IgG titers were 16.22 (15.84-33.42), 5.35 (2.96-13.23), 3.30 (2.18-6.18), 3.14 (1.16-5.70), 2.77 (1.50-4.52), 2.72 (1.76-4.36), 2.01 (1.27-3.51) and 1.94 (1.35-3.09) at one to eight months after SARS-CoV-2 infection, respectively. The results suggested that IgG antibodies increased gradually within two weeks after SARS-CoV-2 infection, then declined gradually at three to seven weeks in SARS-CoV-2 natural infection cases. In SARS-CoV-2 breakthrough cases, IgG antibodies increased rapidly within two weeks, then declined gradually at three to seven weeks after SARS-CoV-2 infection. Additionally, IgG antibodies decreased rapidly within three months, then decreased gradually and remained at a low level within three months after immunization.

Objective: To evaluate the immunity persistence five years later after immunization with Haemophilus influenzae type b (Hib) conjugate vaccine in healthy infants/children aged 3 months to 5 years in China. Methods: The children were subjects who completed the whole-schedule immunization in the phase Ⅲ clinical trial in Lianshui county of Jiangsu povince was selected for the collection of blood samples at 5 years after vaccination from November to December, 2019. The enzyme-linked immunosorbent assay (ELISA) was used to detect Hib polyribosyl-ribitol-phosphate antibody (anti-Hib-PRP), and the long-term/short-term protection rate, geometric mean concentration (GMC) and geometric mean concentration increase fold (GMFI) of serum anti-Hib-PRP were calculated. Results: A total of 580 children were enrolled in this study, of which 158, 207 and 215 belonged to 3-5 month age group, 6-11 month age group and 1-5 year age group, respectively. The short-term (≥0.15 μg/ml)/long-term (≥1.0 μg/ml) protection rates of serum anti-PRP in the three groups after immunization were 89.24%, 90.34% and 98.60%, respectively; the GMC were 3.95 μg/ml, 3.11 μg/ml and 10.01 μg/ml respectively, and the GMFI were 29.04, 11.01 and 3.26 respectively. Conclusions: Hib conjugate vaccine can still have good immunogenicity after 5 years of primary immunization in healthy infants/children aged 3 months to 5 years in China.

Objective: To analyze the impact of metabolic risk factors on the epidemiological characteristics of the reactivation of inactive HBsAg carriers (IHC) and provide effective intervention measures to standardize the management of chronic hepatitis B infections. Methods: Based on the chronic hepatitis B infection cohort established in 2010 in Jiangsu province, six follow-up visits from 2012 to 2020 were conducted to analyze the characteristics and influencing factors of the hepatitis B reactivation of IHC and the impact of metabolic risk factors, including obesity, high blood pressure, diabetes and hyperglycemia. Results: From 2012 to 2020, 2 527 IHC and 17 730 person-years were observed during a median follow-up period of 7.0 person-years. Ninety-eight cases of hepatitis B reactivation, with a cumulative reaction rate, was 3.9%, and the incidence density was 5.53/1 000 person-years. Multivariate Cox proportional risk regression analysis showed that age and baseline HBV DNA were independent risk factors of HBV reactivation. Compared with the patients ≥60 years, 40-49 age group (a HR =2.16, 95% CI: 1.20-3.90) and 20-29 age group (a HR =5.48, 95% CI: 2.07-14.48) were significantly associated with hepatitis B reactivation. Compared with the HBV DNA negative patients at baseline, the risk of hepatitis B reactivation was higher in the group with low HBV DNA level 100-1 999 IU/ml (a HR =1.67, 95% CI: 1.11-2.52). Stratification analysis results showed that compared with those without metabolic risk factors, in the ≥50 age group, patients with ≥2 metabolic risk factors showed adjusted HR of 2.73 (95% CI :1.08-6.96). Conclusions: The risk of hepatitis B being reactive is the persistent existence of IHC in communities in Jiangsu province, especially young adults, low-level HBV DNA carriers, and IHC with ≥2 metabolic risk factors. Follow-up for these IHC should be strengthened to reduce the risk of disease progression by antiviral treatment at the right time.

The COVID-19 outbreak at the end of 2019 has accelerated the development and research for COVID-19 vaccines worldwide. Among the COVID-19 vaccines in clinical trials developed via different platforms, recombinant virus vector-based vaccines have shown excellent immunogenicity and efficacy. However, at the same time, there are serious issues such as vaccine safety and pre-existing antibodies against vectors. This article summarizes the design concept and development history of recombinant virus vector-based vaccines, and focuses on the progress in the clinical studies of vector-based COVID-19 vaccines as well as the challenges, in order to provide reference for the research of recombinant vector-based vaccines.

When the coverage of the vaccinated people reaches a certain percentage of the population, the herd protection will protect the unvaccinated persons. However, the traditional clinical evaluation of vaccines performing individual randomized design fails to evaluate the herd protection of vaccines. Compared with the individual randomized design, the cluster-randomized design can determine the overall protection by the vaccine more comprehensively. It has become increasingly common to perform a cluster-randomized design in clinical trials of vaccines in Phase Ⅲ and Ⅳ clinical trials. However, little is known about the application of cluster randomized design in vaccine clinical trials in China. We, at this moment, do a review of the application of random cluster design in vaccine clinical trials and provide references for future research in China.

Hepatitis B virus (HBV) can cause a variety of hepatitis B-related diseases in infected people, and there is no specific drug for treatment. China, with a large population base, is the country with the heaviest burden of HBV infection in the world. Therefore, hepatitis B vaccination is particularly important in the prevention and control of this disease. However, some vaccinees did not produce effective protective immune response after vaccination according to the recommended hepatitis B vaccine immunization schedule. The purpose of this review is to analyze the influential factors of non/low immune response after hepatitis B vaccination from the aspects of organism and vaccine, and explore the mechanism of non/low immune response, so as to provide scientific basis for the prevention and treatment of hepatitis B in China.

Avian influenza virus (AIV) is a kind of zoonotic virus which can cause acute respiratory infectious diseases. Since the report of the world's first human infection case of avian influenza A (H7N9) virus in China in 2013, close attention has been paid to the virus. AIV spreads widely around the world, and human infection with different types of AIV continues to occur, causing huge economic losses. At present, there are no specific treatment and drugs against the disease, and vaccination is considered as the most promising and effective method to control the human infection with AIV. So far, there are many kinds of veterinary and human vaccines for H7N9 AIV, among which four types of human H7N9 AIV vaccines have entered the clinical trial stage, including virus-like particles vaccine, attenuated live vaccine, inactivated vaccine and DNA vaccine, which have shown good safety and immunogenicity. However, the true efficacies of the AIV vaccines remain unknown because no human vaccines are currently available in the market. In addition, although the existing influenza vaccine has good safety and immunogenicity in the human population, there is no cross-antibody response to H7N9 AIV. This paper summarizes the research progress of AIV etiology and epidemiology, the occupational exposure population investigation, the infection prevention and control strategies, and H7N9 AIV vaccine and H7N9 AIV anthropogenic monoclonal antibody, and discuss the remained problems, challenges and future trends in the research of AVI to improve the understanding of the disease and the prevention and control of global spread of AIV.

Objective: To evaluate and share the novel method for recruiting participants in clinical trials of vaccines in emergency situations. Methods: To publish recruitment notice in local areas of Wuhan through websites and medium, and guide interested persons to log in to the"Clinical Trials of SARS-CoV-2 Vaccine Reservation and Health Declaration System"to appoint and register their health information. The "Health Declaration System" provides each volunteer evaluation and risk levels to preliminarily exclude those who do not meet the inclusion criteria. Researchers review the qualified volunteers by telephone, organize them to go to the vaccination site, and finally conduct a strict medical screening to determine the final subjects. Results: A total of 4 819 people and 5 132 people registered in the Phase Ⅰ and Phase Ⅱ recruitment system respectively, with men 2 912 (60.43%) and 2 887 (56.25%) more than women 1 907 (39.57%) and 2 245 (43.75%), mostly in the 20-39 age group, with 3 211 (66.63%) and 3 966 (77.28%). All 13 districts in Wuhan have interested residents to participate clinical research.The initial qualified rate of the Phase Ⅱ recruitment system was higher than that of Phase Ⅰ, with men 2 047 (70.28%) and 2 135(73.95%), higher than women 1 083 (56.80%) and 1 472 (65.57%); 440 and 689 people were reviewed by telephone in Phase Ⅰ and Phase Ⅱ respectively, and the number of verified volunteers was about 440 (35.00%) and 689 (67.20%); Of the 201 603 people who arrived at the vaccination site, 12 and 26 of them were positive for the SARS-CoV-2 antibody with an antibody positive rate of 6.00% and 4.31% respectively. Conclusion: The novel method for recruiting subjects in this clinical study is efficient and reliable, and the recruitment situation of Phase Ⅰ had set a good example for Phase Ⅱ but the medium-and long-term compliance of subjects and the separation of willingness and behaviors still need to be further studied.

Effectiveness of seasonal influenza vaccines varies greatly during the different flu seasons. Although the WHO assesses and updates influenza vaccine strains every year, the effectiveness of vaccine is sometimes not good. This review explores the various factors that influencing influenza vaccine effects in order to improve the effectiveness of influenza vaccines and provide a scientific basis for influenza vaccination. The results reveal that the degree of matching between epidemic strains and vaccine strains, pre-exposure (natural infection, vaccination), age, and immune status could all affect the vaccine effectiveness.

Vaccine efficacy can be assessed by a randomized placebo-control trial prior to marketing. However, after the marketing of a vaccine, if a placebo-randomized control trial is used to evaluate the efficacy of the vaccine, ethical issues will arise. Therefore, the evaluation of the efficacy of a vaccine after marketing has become a difficult problem in the public health field. In recent years, the research method of test-negative design has been widely used in the world for the evaluations of the efficacies of different post-marketing vaccines, such as influenza vaccine, rotavirus vaccine, cholera vaccine, pneumonia vaccine and EV71 vaccine. However, there are limited reports in the domestic literature on the test-negative design. Therefore, we summarize the basic principles, application steps, advantages and disadvantages of the test-negative design to provide theoretical methods and basis for the future study of test-negative design in China.

Objective: To evaluate the effectiveness of live attenuated influenza vaccine (LAIV) in the prevention of seasonal influenza in children aged 2-17 years. Methods: Literature retrieval of case-control studies on the effectiveness of LAIV against seasonal influenza in children published from January 2003 to November 2018 was conducted through Web of Science, PubMed, and ScienceDirect databases. The Stata 13.1 software was used for Meta-analysis. Results: A total of 14 studies were included in this study, and all were test-negative design (TND) studies. Our Meta-analysis showed that the effectiveness of LAIV in children was 49 % (95 %CI : 40 % -57 % ). Subgroup analysis found that the protection rate of LAIV was 35 % against influenza A (H1N1) pdm09 (95 %CI : 5 % -56 % ), 35 % against influenza A (H3N2) (95 %CI : 21 % -46 % ), and 71 % against influenza B (95 %CI : 55 % -82 % ). The protection rates of trivalent LAIV and quadrivalent LAIV in children were 56 % (95 %CI : 48 % -63 % ) and 44 % (95 %CI : 27 % -57 % ), respectively. The protection rates of LAIV in Europe and North America were 65 % (95 %CI : 47 % -77 % ) and 46 % (95 %CI : 36 % -55 % ), respectively. Conclusion: LAIV has a certain preventive effect on seasonal influenza in children aged 2-17 years.

Original antigenic sin may exist in the influenza virus infection or vaccination, which possibly reduces the protective efficacy in repeated influenza vaccination. This paper reviews the literature on the original antigenic sin and its influence in influenza vaccination, and interprets the possible mechanism of this phenomenon from the three aspects of influenza virus structure, humoral immunity and cellular immunity. A large number of studies have shown that original antigen sin has a negative impact on influenza vaccination, but the evidence disproveing this phenomenon also exist, so multi-center large-scale clinical trials should be conducted to provide evidence-based basis for reaearching whether original antigen sin exists and its effects. in order to provide reference for the development and update of noval influenza vaccines and its formulation of immunization strategies.

Yersiniosis is one of the "other infectious diarrhea" of the notifiable infectious diseases and also an important food-borne disease. However, it lacked the basis or standard for diagnosis. The Chinese Preventive Medicine Association coordinated experienced researchers from National Institute for Communicable Disease Control and Prevention, China CDC and other institutes to produce the group standard entitled "Diagnosis of Yersiniosis" (T/CPMA 005-2019). Based on the principle of "legality, scientificity, advancement, and feasibility" , the standard gives a clear definition for Yerisiniosis, stipulates diagnosis basis, principles and main differential diagnosis and provides two informative appendixes for epidemiological and clinical characteristics and a normative appendix for laboratory detection. The standard provides accurate basis and methods of Yersiniosis diagnosis for hospitals and CDCs at all levels in China. It will solve the problems that Yersiniosis cannot be clearly diagnosed for clinical cases and in the outbreaks.

There are many limitations in evaluating vaccine efficacy by comparing the incidence of clinical endpoint events (such as morbidity, bacterial colonization) between the vaccine group and the control group. Therefore, the researchers put forward the concept of Surrogate of protection to predict vaccine protection with immunological indicators. In 2012, WHO put forward the immunological substitution endpoint of pneumococcal vaccine, using 0. 35 μg/ml as the protective antibody level of pneumococcal vaccine. But subsequent studies have found that using this threshold to assess all vaccine serotypes may not be accurate.

Maternal immunization is an immune strategy that protects both mothers and early-life infants from disease by the vaccination of pregnant women. The effect of maternal immunization is influenced by the types of vaccines, the timing of vaccination, the subtypes of antibodies induced by vaccines, and the health status of mothers themselves. Inactivated influenza vaccination during pregnancy and DPT vaccination during the third trimester of pregnancy have been widely used in the world, while Hepatitis B vaccine, pneumococcal and meningococcal vaccines also show good efficacy and safety in pregnant women. This article reviews the research progress of Maternal Immunization in order to provide a reference for Maternal Immunization planning and policymaking in China.

Genes play an important role in the immune system response, and different gene loci may result in different vaccine immune response rates. This review focuses on the correlation between gene polymorphisms and vaccine immune response in order to investigate the influence of gene polymorphisms on the immune response to vaccines. It discusses the effect of an individual's immune response after vaccination at genetic level and provides a scientific basis for individualized immune development strategies. It reveals that human leukocyte antigen genes, various cytokines and their receptor genes, and Toll-like receptor genes all affect the vaccine immune response.

Due to immature development of the immune system, preterm infants are at increased risk of infections from vaccine-preventable diseases. But at the same time, premature vaccination may not induce a good immune response because of the incomplete development of the neonatal immune system, and may cause serious adverse reactions risk due to the poor immune tolerance, thus vaccination of preterm infants at the appropriate time is the key to reducing the risk of infectious disease and obtaining vaccine protection. At present, it is generally recommended that the gestational age and birth weight should be considered in the vaccination of preterm infants. The timing, type and even the immunization schedule of the vaccine should be differ from that of the full term infants. However, there is a lack of research results and data on immunization program in preterm infants in China, and there is still no provided universal guidelines for their vaccine immunization. This article aims to summarize the guidelines and clinical trials of vaccination of preterm infants in foreign countries, and to provide reference for the formulation and implementation of immunization strategies for preterm infants in China.

The importance of vaccine on public health is related to the herd protection related to the levels of vaccine coverage, which directly influences the vaccinated individuals as well as the unvaccinated community. Reaching the level of herd protection by increasing vaccine coverage is the basic strategy to eradicate related infectious diseases. Again, herd protection has played an important role in public health practices. With the increasing interests in estimating the vaccine herd protection, we however, have seen only few relevant papers including observational population-based and cluster-randomized clinical trials reported in China. We hope to discuss the study designs for evaluating the vaccine herd protection in order to generate evidence-based related research in this field.

Due to the tumor malignancy or immunosuppressive treatment, patients with cancer in general are more susceptible to vaccine-preventable infections. The types, timing, dose of vaccination or even the immunization program for them may differ from those for the normal persons. At present, it is recommended to use inactivated vaccines for patients with cancer rather than attenuated live vaccines, Vaccinations should be avoided during immunosuppressive therapy; patients with cancer should receive double dosage of hepatitis B vaccines and two doses of inactivated influenza vaccines yearly. This paper summarizes the progress in clinical trials of vaccination for cancer patients in foreign countries, and provide reference for the development and implementation of vaccination strategy for cancer patients in China.

Objective: To understand the epidemiological characteristics and influencing factors related to HBeAg sero-clearance in chronic hepatitis B patients so as to provide evidence for regular management on chronic HBV patients. Methods: From 2012 to 2014, a cohort study was conducted among HBeAg positive chronic HBV patients in Jiangsu province. Association between the characteristics and incidence of HBeAg sero-clearance was analyzed by Cox regression method. The changing trend on HBV DNA between patients with HBeAg sero-clearance and those with persistent HBeAg positive status was compared by repeated measure data variance analysis method. Results: In 2012, there were 721 HBeAg positive hepatitis B patients aged (45.2 ± 14.2) years enrolled in this study. By 2014, the follow-up observation period was 1 058 person-years, and 393 cases had lost their HBeAg status, with the rate as 37.2/100 person-years. The HBeAg sero-clearance rate was 32.4/100 person-years in hepatitis B patients who received antiviral treatment. The probability of HBeAg clearance in HBeAg positive hepatitis B patients aged ≥60 year (62.0/100 person-years) was higher than those of aged <20 year (7.0/100 person-years). The rate of HBeAg sero-clearance in HBeAg positive patients with HBV DNA <20 000 IU/ml (75.8/100 person-years) was higher than those whose HBV DNA were ≥200 000 IU/ml (16.1/100 person-years). By Cox regression analysis, the HBV DNA level was an important influencing factor on the progress of HBeAg sero-clearance. Patients with HBV DNA levle as ≥200 000 IU/ml, had a lower HBeAg clearance rate ( HR =0.18, 95 %CI : 0.13-0.23, P <0.001). Compared to the persistent HBeAg positive group, HBV DNA showed a more dramatic fall in the HBeAg-lost group ( P <0.001). Conclusion: The rate of HBeAg sero-clearance among HBeAg positive hepatitis B patients was correlated with age and HBV DNA status of the patients that called for comprehensive management and intervention programs to develop for the HBeAg positive hepatitis B patients with different characteristics.

Objective: To understand characteristics and influencing factors of reversion of HBeAg in chronic hepatitis B patients with HBeAg sero-conversion, and provide epidemiological evidence for the regular management of chronic hepatitis B patients. Methods: From 2012 to 2014, a cohort study was conducted among the chronic hepatitis B patients with sero-conversion of HBeAg in Jiangsu province. Association between participants' demographics, ALT, HBV DNA and incidence of HBeAg reversion was analyzed by Cox regression model. HBV DNA changing trend between patients with HBeAg reversion and patients with persistent HBeAg sero-conversion was compared by repeated measure data variance analysis. Results: In 2012, there were 5 068 HBeAg seroconverted chronic hepatitis B patients aged (51.9 ± 12.8) years enrolled. By 2014, HBeAg had reversed in 121 cases with the rate of 1.3/100 person-years. The probability of HBeAg reversion decreased with the age of the patients. By Cox regression analysis, HBV DNA level was an important influencing factor for the progress of HBeAg reversion. The patients with HBV DNA≥200 000 IU/ml had a higher HBeAg reversion rate DNA (3.8/100 person-years) than those with HBV DNA <2 000 IU/ml (1.1 person-years) ( HR =3.44, 95 % CI : 1.91-6.20, P =0.000). Compared with the persistent HBeAg sero-conversion group, HBV DNA and ALT showed a more dramatic increase in the HBeAg reversion group ( P =0.000). Conclusions: There was a certain HBeAg reversion rate in chronic hepatitis B patients with HBeAg sero-conversion. Younger chronic CHB patients with HBeAg sero-conversion and those with higher HBV DNA lever had higher HBeAg reversion rate. Following up and management of chronic CHB patients with HBeAg sero-conversion is important and helpful for the control of hepatitis B.

Objective: To understand epidemiological characteristics and influencing factors of hepatitis B virus (HBV) carriers progressing to chronic hepatitis B in Jiangsu, and provide evidence for regular management of HBV carriers. Methods: From 2012 to 2014, a cohort study was conducted among the HBV carriers in an area in Jiangsu province. Association between HBV carriers' demographics, HBeAg level and HBV DNA detection result and incidence of chronic hepatitis B was analyzed by Cox regression analyses. Results: In 2012, a total of 4 069 HBV carriers aged (52.0±12.8) years were surveyed. By 2014, chronic hepatitis B had developed in 1 444 cases, with the rate of 21.0/100 person-years. Cox regression analysis indicted that, in addition to gender, HBV DNA level was an important influencing factor for the incidence of chronic hepatitis B ( P <0.05). In HBeAg positive carriers progressing to chronic hepatitis, 40.7% had HBeAg seroconversion, and reversion of HBeAg occurred in 1.7% of HBeAg negative carriers. Conclusion: Chronic hepatitis B developed in more than 1/5 (21.0/100 person-years) of HBV carriers in the surveyed area in Jiangsu. It is suggested to conduct regular ALT, HBV DNA detection and B ultrasonic examination in HBV carriers for the early detection of chronic hepatitis B.

Objective: To evaluate the effects of blocking transmission of HBV from mother to infant in Jiangsu, and discuss influencing factors related to development of chronic HBV infection in children of HBsAg positive mother. Methods: HBsAg positive mothers delivered during 2010-2015 in three counties of Jiangsu (Zhangjiagang, Danyang and Taixing) and their neonates were included in the study. The neonates were vaccinated with hepatitis B vaccine (10 μg) and hepatitis B immunoglobin (100 units) within 24 hours after birth. Blood samples were collected from the infants 7 months later, and serum HBsAg, anti-HBs and anti-HBc were detected by Abbott particles chemiluminescence. Results: A total of 2 099 children aged 7-52 months were surveyed, of whom 34 (1.62 % ) developed chronic HBV infection. Logistic regression analysis showed that mother HBeAg positivity ( RR =4.997, 95 % CI : 2.408-10.370) was the independent risk factors of mother-to-infant transmission of HBV, while elder delivery age ( RR =0.264, 95 % CI : 0.101-0.691) was independent protective factors of HBV transmission. Among the other 2 065 uninfected children, 9.7 % had anti-HBs level less than 10 mIU/ml, 35.4 % between 10 and 100 mIU/ml, and 54.9 % higher than 100 mIU/ml. The anti-HBs positive rate was 90.3 % and the anti-HBc positive rate was 13.7 % . The positive rate and geometric mean titers (GMT) of anti-HBs reached the peaks at 7-12 months after birth, and decreased with the age. Conclusions: The current immunological strategy of Jiangsu has good protective efficacy for the interruption of perinatal transmission of HBV. Mother HBeAg positivity is the major risk factor for perinatal blocking failure. Children with effective immunization still need to be monitored for anti-HBs and revaccinated if necessary.

Objective: To construct a RNA interference lentiviral vector aimed at human ARK5 (AMPK-related protein kinase 5) gene and explore its effect on the biologic behavior of human gastric cancer SGC7901 cells., Methods: Targeting human ARK5 mRNA coding sequence, we designed three specific short hairpin RNAs (shRNAs) and constructed the lentiviral vector, then infected human gastric cancer SGC7901 cells with this vector. Afterwards, we used qPCR and Western blot for detecting the silencing effect on ARK5 gene, MTT colorimetric assay to measure the cell proliferation, cell scratch test for cell migration and Transwell for cell invasion, and flow cytometry analysis for apoptosis in cells treated with glucose starvation and TNF-α., Results: Sequencing proved that the recombinant lentiviral vector containing ARK5-shRNA-3 was constructed successfully. Real time fluorescent quantitative PCR assay showed that the expression abundance of ARK5 gene in the normal control group, negative control group and ARK5-shRNA-3 infected group were 1.002+ 0.082, 1.001+ 0.050 and 0.140+ 0.003, respectively, showing a statistically significant difference (P<0.01). Cell scratch test showed that the cell migration rate of ARK5-shRNA-3 infected group was (38.5+ 4.3)%, significantly lower than that of the normal control group [(72.4+ 6.4)%] and negative control group [(75.1+ 7.1)%, P<0.01]. The results of Transwell test showed that the number of penetrating cells in the normal control group, negative control group and ARK5-shRNA-3 transfection group were 257.4±12.3, 245.7±11.6, 112.5±7.8, with a significant difference (P<0.01). After glucose starvation and TNF-α-treatment for 24 h, the cell death rate of the normal control group, negative control group and ARK5-shRNA-3 group were (11.7±3.2)%, (12.3±2.6)% and (30.8±4.3)%, respectively, showing that the cell apoptosis rate of ARK5-shRNA-3 transfected group was significantly higher than that of the normal control and negative control groups (P<0.01)., Conclusions: We have successfully constructed a recombinant lentiviral vector which can efficiently silence ARK5 gene. Using it we can inhibit the proliferation, migration, invasion of tumor cells, and promote cell apoptosis under the condition of TNF-α treatment and glucose starvation.

Assignment of the 1H and 31P NMR spectra of a phosphorodithioate modified oligonucleotide decamer duplex, d(CGCTTpS2-AAGCG)2 (10-mer-S; a site of dithioate substitution is designated with the symbols pS2-), was achieved by two-dimensional homonuclear TOCSY, NOESY and 1H-31P Pure Absorption phase Constant time (PAC) heteronuclear correlation spectroscopy. In contrast to the parent palindromic decamer sequence (1) which has been shown to exist entirely in the duplex B-DNA conformation under comparable conditions (100 mM KCl), the dithiophosphate analogue forms a hairpin loop. However, the duplex form of the dithioate oligonucleotide can be stabilized at lower temperatures, higher salt and strand concentration. The solution structure of the decamer duplex was calculated by an iterative hybrid relaxation matrix method (MORASS) combined with 2D NOESY-distance restrained molecular dynamics. These backbone modified compounds, potentially attractive antisense oligonucleotide agents, are often assumed to possess similar structure as the parent nucleic acid complex. Importantly, the refined structure of the phosphorodithioate duplex shows a significant deviation from the parent unmodified, phosphoryl duplex. An overall bend and unwinding in the phosphorodithioate duplex is observed. The structural distortion of the phosphorodithioate duplex was confirmed by comparison of helicoidal parameters and groove dimensions. Especially, the helical twists of the phosphorodithioate decamer deviate significantly from the parent phosphoryl decamer. The minor groove width of phosphorodithioate duplex 10-mer-S varies between 8.4 and 13.3 A which is much wider than those of the parent phosphoryl decamer d(CGCTTAAGCG)2 (4.2 approximately 9.4 A). The larger minor groove width of 10-mer-S duplex contributes to the unwinding of the backbone and indicates that the duplex has an overall A-DNA-like conformation in the region surrounding the dithiophosphate modification.