Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia.

BACKGROUND: The initial cases of novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, Hubei Province, China, in December 2019 and January 2020. We analyzed data on the first 425 confirmed cases in Wuhan to determine the epidemiologic characteristics of NCIP. METHODS: We collected information on demographic characteristics, exposure history, and illness timelines of laboratory-confirmed cases of NCIP that had been reported by January 22, 2020. We described characteristics of the cases and estimated the key epidemiologic time-delay distributions. In the early period of exponential growth, we estimated the epidemic doubling time and the basic reproductive number. RESULTS: Among the first 425 patients with confirmed NCIP, the median age was 59 years and 56% were male. The majority of cases (55%) with onset before January 1, 2020, were linked to the Huanan Seafood Wholesale Market, as compared with 8.6% of the subsequent cases. The mean incubation period was 5.2 days (95% confidence interval [CI], 4.1 to 7.0), with the 95th percentile of the distribution at 12.5 days. In its early stages, the epidemic doubled in size every 7.4 days. With a mean serial interval of 7.5 days (95% CI, 5.3 to 19), the basic reproductive number was estimated to be 2.2 (95% CI, 1.4 to 3.9). CONCLUSIONS: On the basis of this information, there is evidence that human-to-human transmission has occurred among close contacts since the middle of December 2019. Considerable efforts to reduce transmission will be required to control outbreaks if similar dynamics apply elsewhere. Measures to prevent or reduce transmission should be implemented in populations at risk. (Funded by the Ministry of Science and Technology of China and others.).

An evaluation index system for regional mobile SARS-CoV-2 virus nucleic acid testing capacity in China: a modified Delphi consensus study.

BACKGROUND: Large-scale detection has great potential to bring benefits for containing the COVID-19 epidemic and supporting the government in reopening economic activities. Evaluating the true regional mobile severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus nucleic acid testing capacity is essential to improve the overall fighting performance against this epidemic and maintain economic development. However, such a tool is not available in this issue. We aimed to establish an evaluation index system for assessing the regional mobile SARS-CoV-2 virus nucleic acid testing capacity and provide suggestions for improving the capacity level. METHODS: The initial version of the evaluation index system was identified based on massive literature and expert interviews. The Delphi method questionnaire was designed and 30 experts were consulted in two rounds of questionnaire to select and revise indexes at all three levels. The Analytic Hierarchy Process method was used to calculate the weight of indexes at all three levels. RESULTS: The evaluation index system for assessing the regional mobile SARS-CoV-2 virus nucleic acid testing capacity, including 5 first-level indexes, 17 second-level indexes, and 90 third-level indexes. The response rates of questionnaires delivered in the two rounds of consultation were 100 and 96.7%. Furthermore, the authority coefficient of 30 experts was 0.71. Kendall's coordination coefficient differences were statistically significant (P < 0.001). The weighted values of capacity indexes were established at all levels according to the consistency test, demonstrating that 'Personnel team construction' (0.2046) came first amongst the five first-level indexes, followed by 'Laboratory performance building and maintenance' (0.2023), 'Emergency response guarantee' (0.1989), 'Information management system for nucleic acid testing resources' (0.1982) and 'Regional mobile nucleic acid testing emergency response system construction' (0.1959). CONCLUSION: The evaluation system for assessing the regional mobile SARS-CoV-2 virus nucleic acid testing capacity puts forward a specific, objective, and quantifiable evaluation criterion. The evaluation system can act as a tool for diversified subjects to find the weak links and loopholes. It also provides a measurable basis for authorities to improve nucleic acid testing capabilities.

Associations between home renovation and asthma, allergic rhinitis, and eczema among preschool children in Wuhan, China.

To investigate the potential associations between household renovation and allergic diseases among preschool children in Wuhan, we conducted a large cross-sectional questionnaire survey among 9455 preschool children aged 3-6 years in Wuhan during November to December 2019. Data on demographics, health status, and home decoration conditions were analysed based on a questionnaire. Compared with tiles/stone/cement floor covering, the use of composite floor significantly increased the risk of diagnosed rhinitis and eczema among children (rhinitis: AOR, 95% CI: 1.36, 1.06-1.73; eczema: AOR, 95% CI: 1.47, 1.17-1.85). Household renovation had significant associations with diagnosed eczema (within 1 year before pregnancy: AOR, 95% CI: 1.34, 1.20-1.50; during pregnancy: AOR, 95% CI: 1.25, 1.08-1.44). This study suggests that use of artificial synthetic materials in home renovation during early childhood and pregnancy may be potential risk factors for childhood asthma, allergic rhinitis, and eczema.

Reproductive toxicity of cadmium in pubertal male rats induced by cell apoptosis.

Cadmium (Cd) is a heavy metal that is widely present in modern industrial production. It is a known, highly toxic environmental endocrine disruptor. Long-term exposure to Cd can cause varying degrees of damage to the liver, kidney, and reproductive system of organisms, especially the male reproductive system. This study aimed to explore the mechanism of Cd toxicity in the male reproductive system during puberty. Eighteen healthy 6-week-old male Sprague-Dawley rats were randomly divided into three groups (control group, low-dose group, and high-dose group) according to their body weight, with six in each group. Cd (0, 1, and 3 mg/kg/day) was given by gavage for 28 consecutive days. The results showed that Cd exposure to each dose group caused a decrease in the testicular organ coefficient and sperm count, compared with the control group. Cd exposure resulted in significant changes in testicular morphology in the 3 mg/kg/day Cd group. In the 1 and 3 mg/kg/day Cd groups, serum testosterone decreased and apoptosis of testicular cells increased significantly (p < 0.05). In addition, compared with the control group, the activity of glutathione peroxidase and superoxide dismutase in each Cd exposure dose group decreased, but the content of malondialdehyde in the high-dose, 3 mg/kg/day Cd treatment group significantly increased (p < 0.05). Although Cd exposure caused an increase in the messenger RNA (mRNA) levels of Bcl-2, Caspase-3 and Caspase-9 in the testicular tissues (p < 0.05), Bcl-2 expression was unchanged (p > 0.05). The expression level of Akt mRNA in testicular tissue of rats in the high-dose 3 mg/kg/day Cd group was increased (p < 0.05). Our data suggest that Cd affected testosterone levels, and apoptosis was observed in spermatids.

Effectiveness and Safety of an Inactivated Enterovirus 71 Vaccine in Children Aged 6-71 Months in a Phase IV Study.

BACKGROUND: Evaluation of a licensed inactivated enterovirus type 71 (EV71) vaccine is needed in a phase IV study with a large population to identify its effectiveness and safety for further application. METHODS: An open-label, controlled trial involving a large population of 155 995 children aged 6-71 months was performed; 40 724 were enrolled in the vaccine group and received 2 doses of inactivated EV71 vaccine at an interval of 1 month, and the remaining children were used as the control group. The EV71-infected cases with hand, foot, and mouth disease were monitored in the vaccine and control groups during a follow-up period of 14 months since the 28th day postinoculation through the local database of the Notifiable Infectious Diseases Network. The effectiveness of the vaccine was estimated by comparing the incidence density in the vaccine group versus that in the control group based upon EV71-infected patients identified via laboratory testing. In parallel, the active and passive surveillance for safety of the vaccine was conducted by home or telephone visits and by using the Adverse Event Following Immunization (AEFI) system, respectively. RESULTS: An overall level of 89.7% (95% confidence interval, 24.0-98.6%) vaccine effectiveness against EV71 infection and a 4.58% rate of reported adverse events were observed. Passive surveillance demonstrated a 0.31% rate of reported common minor reactions. CONCLUSIONS: The clinical protection and safety of the EV71 vaccine were demonstrated in the immunization of a large population. CLINICAL TRIALS REGISTRATION: NCT03001986.

Epidemiological characteristics and transmissibility of shigellosis in Hubei Province, China, 2005 - 2017.

BACKGROUND: Shigellosis is one of the main diarrhea diseases in developing countries. However, the transmissibility of shigellosis remains unclear. METHODS: We used the dataset of shigellosis cases reported between January 2005 and December 2017, from Hubei Province, China. A mathematical model was developed based on the natural history and the transmission mechanism of the disease. By fitting the data using the model, transmission relative rate from person to person (b) and from reservoir to person (bw), and the effective reproduction number (Reff) were estimated. To simulate the contribution of b and bw during the transmission, we performed a "knock-out" simulation in four scenarios: A) b = 0 and bw = 0; B) b = 0; C) bw = 0; D) control (no intervention). RESULTS: A total of 130,770 shigellosis cases were reported in Hubei province, among which 13 cases were dead. The median annual incidence was 19.96 per 100,000 persons (range: 5.99 per 100,000 persons - 29.47 per 100,000 persons) with a decreased trend (trend χ2 = 25,470.27, P < 0.001). The mean values of b and bw were 0.0898 (95% confidence interval [CI]: 0.0851-0.0946) and 1.1264 × 10- 9 (95% CI: 4.1123 × 10- 10-1.8416 × 10- 9), respectively. The "knock-out" simulation showed that the number of cases simulated by scenario A was almost the same as scenario B, and scenario C was almost the same as scenario D. The mean value of Reff of shigellosis was 1.19 (95% CI: 1.13-1.25) and decreased slightly with a Linear model until it decreased to an epidemic threshold of 0.99 (95% CI: 0.65-1.34) in 2029. CONCLUSIONS: The incidence of shigellosis is still in high level. The transmissibility of the disease is low in Hubei Province. The transmission would be interrupted in the year of 2029.

Status of tuberculosis-related stigma and associated factors: a cross-sectional study in central China.

OBJECTIVES: Tuberculosis (TB) poses a significant challenge to public health worldwide. Stigma is a major obstacle to TB control by leading to delay in diagnosis and treatment non-adherence. This study aimed to evaluate the status of TB-related stigma and its associated factors among TB patients in China. METHODS: Cross-sectional survey. Thus, 1342 TB patients were recruited from TB dispensaries in three counties in Hubei Province using a multistage sampling method and surveyed using a structured anonymous questionnaire including validated scales to measure TB-related stigma. A generalised linear regression model was used to identify the factors associated with TB-related stigma. RESULTS: The average score on the TB-related Stigma Scale was 9.33 (SD = 4.25). Generalised linear regression analysis revealed that knowledge about TB (ß = -0.18, P = 0.0025), family function (ß = -0.29, P < 0.0001) and doctor-patient communication (ß = -0.32, P = 0.0005) were negatively associated with TB-related stigma. CONCLUSIONS: TB-related stigma was high among TB patients in China. Interventions concentrating on reducing TB patients' stigma in China should focus on improving patients' family function and patients' knowledge about TB.

Functional Genetic Variants of PPARx03B3; and PPARα Encoding Peroxisome Proliferator-Activated Receptors and Susceptibility to Ischemic Stroke in Chinese Han Population.

BACKGROUND: PPARx03B3; and PPARα belong to a receptor family of ligand-activated transcription factors involved in the regulation of inflammation, cellular glucose uptake, protection against atherosclerosis and endothelial cell function. Through these effects, they might be involved with the ischemic stroke (IS). METHODS: One thousand two hundred ninety-six subjects from the Chinese Han Population were chosen to assess the nature of the functional polymorphisms of PPARs and any links with IS. Multivariate logistic regression analysis was used to examine the association between PPARx03B3; and PPARα genotypes and a diagnosis of IS. RESULTS: Pro/Ala carriage may be associated with the decreased risk of IS in Hans (OR 0.542, 95% CI 0.346-0.850). The 162Val allele frequency at the DNA-binding region of PPARα was extremely rare in Chinese Han population. CONCLUSIONS: PPARx03B3; 12Pro/Ala resulting in an amino acid exchange in N-terminal sequence may be an independent protective factor for IS in the Chinese Han population. However, more populations are warranted to validate our findings.

Zwitterionic Surfactant Modified Acetylene Black Paste Electrode for Highly Facile and Sensitive Determination of Tetrabromobisphenol A.

A electrochemical sensor for the highly sensitive detection of tetrabromobisphenol A (TBBPA) was fabricated based on acetylene black paste electrode (ABPE) modified with 3-(N,N-Dimethylpalmitylammonio) propanesulfonate (SB3-16) in this study. The peak current of TBBPA was significantly enhanced at SB3-16/ABPE compared with unmodified electrodes. To further improve the electrochemical performance of the modified electrode, corresponding experimental parameters such as the length of hydrophobic chains of zwitterionic surfactant, the concentration of SB3-16, pH value, and accumulation time were examined. The peak currents of TBBPA were found to be linearly correlated with its concentrations in the range of 1 nM to 1 µM, with a detection limit of 0.4 nM. Besides, a possible mechanism was also discussed, and the hydrophobic interaction between TBBPA and the surfactants was suggested to take a leading role in enhancing the responses. Finally, this sensor was successfully employed to detect TBBPA in water samples.

Consumption of hot beverages and foods and the risk of esophageal cancer: a meta-analysis of observational studies.

BACKGROUND: Previous studies have mostly focused on the effects of specific constituents of beverages and foods on the risk of esophageal cancer (EC). An increasing number of studies are now emerging examining the health consequences of the high temperature of beverages and foods. We conducted a meta-analysis to summarize the evidence and clarify the association between hot beverages and foods consumption and EC risk. METHODS: We searched the PubMed, Embase, and Web of Science databases for relevant studies, published before May 1, 2014, with the aim to estimate the association between hot beverage and food consumption and EC risk. A random-effect model was used to pool the results from the included studies. Publication bias was assessed by using the Begg test, the Egger test, and funnel plot. RESULTS: Thirty-nine studies satisfied the inclusion criteria, giving a total of 42,475 non-overlapping participants and 13,811 EC cases. Hot beverage and food consumption was significantly associated with EC risk, with an odds ratio (OR) of 1.82 (95% confidence interval [CI], 1.53-2.17). The risk was higher for esophageal squamous cell carcinoma, with a pooled OR of 1.60 (95% CI, 1.29-2.00), and was insignificant for esophageal adenocarcinoma (OR: 0.79; 95% CI: 0.53-1.16). Subgroup analyses suggests that the association between hot beverage and food consumption and EC risk were significant in Asian population (OR: 2.06; 95% CI: 1.62-2.61) and South American population (OR: 1.52; 95% CI: 1.25-1.85), but not significant in European population (OR: 0.95; 95% CI: 0.68-1.34). CONCLUSIONS: Hot beverage and food consumption is associated with a significantly increased risk of EC, especially in Asian and South American populations, indicating the importance in changing people's dietary habits to prevent EC.

Association Between ACE2 and Lung Diseases.

Angiotensin-converting enzyme 2 (ACE2) is an important regulator of the Renin-Angiotensin System (RAS). Additionally, it has been identified as a functional receptor for the Coronavirus. Research indicates that ACE2 plays a role in the regulation of cardiovascular systems by modulating blood pressure and electrolyte balance. Its role in pulmonary diseases has also garnered significant attention due to the widespread prevalence of Coronavirus. There is solid evidence linking ACE2 to other pulmonary diseases, including chronic obstructive pulmonary disease, acute respiratory distress syndrome, allergic asthma, among others. However, the exact pathological and physiological mechanisms of ACE2 in these diseases remain elusive. Our research aims to review and explore the latest advancements in ACE2-related studies in pulmonary diseases. These findings have the potential to open new avenues for utilizing ACE2 as a potential biomarker for early diagnosis and monitoring of pulmonary diseases.

Safety of primary immunization using inactivated SARS-CoV-2 vaccine (CoronaVac®) among population aged 3 years and older in a large-scale use: A multi-center open-label study in China.

OBJECTIVE: To evaluate the safety of primary immunization using CoronaVac® among population aged 3 years and above in a large-scale use. METHOD: A multi-center open-label study was carried out in 11 provinces of China. Individuals aged 3 years and older who had no history of COVID-19 vaccination or had received only one dose of CoronaVac® were enrolled in this study. Adults and elderly with or without underlying medical conditions(UMCs) were also recruited. Eligible participants received one or two doses of CoronaVac® with an interval of 28 days. Demographic information, vaccination and the occurrence of adverse events were recorded by participants or guardians using data collection system designed for this study. All adverse events occurred within 6 months after the second dose of vaccination were collected. The incidence of adverse events that cannot be ruled out as being caused by the vaccine were calculated to assess the safety of CoronaVac®. This study is registered with ClinicalTrials. Gov (NCT04911790 and NCT04992208). RESULTS: A total of 162,691 participants have been included in this study and 89.50 % had finished primary immunization. Among adults and elderly, people with UMCs accounted for 25.85 %, with the top five disease being hypertension, diabetes, chronic gastritis, coronary heart disease(CHD) and kidney stone. The overall incidence of adverse reactions (ARs) within 6 months after the second vaccination was 2.70 %, with incidence for children and adolescents, adults, and elderly being 2.03 %, 3.46 %, and 1.90 %, respectively. Most ARs were mild (grade 1). Pain at the injection sites, fatigue, induration/swelling, and headache were the most common symptoms, occurring in 1.64 %, 0.46 %, 0.31 % and 0.24 %, respectively. No serious adverse events related to vaccines were reported. No adverse events of special interest (AESIs) were identified. For children and adolescents, children aged 3-5 years had the highest incidence of ARs of 3.29 %. The incidence of ARs among those aged 18 years and older with and without UMCs were 2.81 % and 2.99 %, respectively, with no statistical significance between two groups(P = 0.089). And people with coronary heart disease had higher AR incidence compared to those with other UMCs, but the most common symptoms was pain at the injection site. CONCLUSION: CoronaVac® is safe in a large-scale use and shows well-tolerance for children and adolescents and people with underlying medical conditions. Further studies need to be conducted to explore the relation of ARs incidence to age or different kinds of UMCs.

The Progress of the Prevention and Treatment of Vitamin D to Tuberculosis.

The progressions of a number of lung diseases, including acute lung injury, cystic fibrosis, asthma, chronic obstructive pulmonary disease, pneumonia and tuberculosis (TB) are found to be highly associated with inflammatory responses. As a signaling nutrient, Vitamin D modulates the activities of dendritic cells, monocytes/macrophages, T and B cells, and tissue epithelial cells in the body to induce inflammatory responses and boost immune functions. Given the high prevalence of vitamin D deficiency among pulmonary insufficiency and inflammation-related cases, researchers indicated vitamin D supplementation could have a potential role in the prevention and treatment of lung disease, especially tuberculosis. In this paper, we reviewed published studies on the role of vitamin D in the prevention and treatment of tuberculosis. The paper identified vitamin D's potential as an adjunctive therapy and demonstrated its safety so as to provide an impetus for further studies and clinical applications.

Applying the Moving Epidemic Method to Establish the Influenza Epidemic Thresholds and Intensity Levels for Age-Specific Groups in Hubei Province, China.

BACKGROUND: School-aged children were reported to act as the main transmitter during influenza epidemic seasons. It is vital to set up an early detection method to help with the vaccination program in such a high-risk population. However, most relative studies only focused on the general population. Our study aims to describe the influenza epidemiology characteristics in Hubei Province and to introduce the moving epidemic method to establish the epidemic thresholds for age-specific groups. METHODS: We divided the whole population into pre-school, school-aged and adult groups. The virology data from 2010/2011 to 2017/2018 were applied to the moving epidemic method to establish the epidemic thresholds for the general population and age-specific groups for the detection of influenza in 2018/2019. The performances of the model were compared by the cross-validation process. RESULTS: The epidemic threshold for school-aged children in the 2018/2019 season was 15.42%. The epidemic thresholds for influenza A virus subtypes H1N1 and H3N2 and influenza B were determined as 5.68%, 6.12% and 10.48%, respectively. The median start weeks of the school-aged children were similar to the general population. The cross-validation process showed that the sensitivity of the model established with school-aged children was higher than those established with the other age groups in total influenza, H1N1 and influenza B, while it was only lower than the general population group in H3N2. CONCLUSIONS: This study proved the feasibility of applying the moving epidemic method in Hubei Province. Additional influenza surveillance and vaccination strategies should be well-organized for school-aged children to reduce the disease burden of influenza in China.

The Potential Role of Vitamin D in the Development of Tuberculosis in Chinese Han Population: One Case-Control Study.

Background and aims: Spinal serum 25-hydroxyvitamin D [25[OH]D] status plays an important role in mediating innate immune responses by acting as a cofactor for induction of antimycobacterial activity and is thus involved in the development of Tuberculosis (TB). Results reported regarding the association of vitamin D with TB remained controversial. We aimed to identify any common association between 25[OH]D status and TB in the Chinese Han population. Methods: 280 subjects (70 TB patients and 210 matched controls) were recruited. TB cases were diagnosed based on the presence of acid-fast bacilli on smears from sputum and MTB isolation. Healthy controls were randomly selected from four local community-based populations. 25[OH]D was detected by electrochemiluminescence immunoassay (ECLIA) on Roche Elecsys before the initial treatment. Multivariable logistic regression analysis was used to examine the association of Vitamin D with TB. Results: There was no significant difference in the serum vitamin D level between total cases and controls, but we found a strong tendency toward a higher serum vitamin D level in male population (P < 0.05) with TB but not in females. High serum vitamin D increased the risk of TB in the Chinese Han population (OR = 1.035, 95%CI: 1.001-1.070, P < 0.05). The serum vitamin D level was significantly decreased with age increasing in cases and controls (all P < 0.001). Conclusions: High serum vitamin D may be an independent risk factor for TB in the Chinese Han population.

China is implementing the national nutrition plan of action.

With the transformation of Chinese economic and social structure, the social determinants of nutrition have undergone significant changes, which have a great influence on the dietary patterns and nutrition status of its population. The transition in the structure of nutrition intake in China can be characterized by a rapid trend in food accessibility, affordability, and diversity. However, challenges, such as the triple burden of malnutrition (undernourishment, micronutrient deficiencies, and obesity), still seriously threaten the population's health. To approach the targets for the "Healthy China 2030," the General Office of the State Council of the People's Republic of China issued the National Nutrition Plan of Action (2017-2030), which specifies multi-sectoral transdisciplinary measures to improve population nutrition status. In our study, we recognized the role of the National Nutrition Plan of China in responding to the call for the Sustainable Development Goals (SDGs). Under the global- and country-level targets, this paper presented six primary intervention measures specified in the National Nutrition Plan of Action in China, highlighting the importance of collaborative actions for participants in all sectors.

The research progress of Chikungunya fever.

Chikungunya fever, an acute infectious disease caused by Chikungunya virus (CHIKV), is transmitted by Aedes aegypti mosquitoes, with fever, rash, and joint pain as the main features. 1952, the first outbreak of Chikungunya fever was in Tanzania, Africa, and the virus was isolated in 1953. The epidemic has expanded from Africa to South Asia, the Indian Ocean islands and the Americas, and is now present in more than 100 countries and territories worldwide, causing approximately 1 million infections worldwide each year. In addition, fatal cases have been reported, making CHIKV a relevant public health disease. The evolution of the virus, globalization, and climate change may have contributed to the spread of CHIKV. 2005-2006 saw the most severe outbreak on Reunion Island, affecting nearly 35% of the population. Since 2005, cases of Chikungunya fever have spread mainly in tropical and subtropical regions, eventually reaching the Americas through the Caribbean island. Today, CHIKV is widely spread worldwide and is a global public health problem. In addition, the lack of a preventive vaccine and approved antiviral treatment makes CHIKV a major global health threat. In this review, we discuss the current knowledge on the pathogenesis of CHIKV, focusing on the atypical disease manifestations. We also provide an updated review of the current development of CHIKV vaccines. Overall, these aspects represent some of the most recent advances in our understanding of CHIKV pathogenesis and also provide important insights into the current development of CHIKV and potential CHIKV vaccines for current development and clinical trials.

Safety, immunogenicity, and immune persistence of two inactivated COVID-19 vaccines replacement vaccination in China: An observational cohort study.

BACKGROUND: To mitigate a national shortage of WIBP-CorV COVID-19 vaccine, China's regulator approved administering BBIBP-CorV after WIBP-CorV for completion of a primary series. In a pragmatic observational study, we compared immunogenicity and safety of a primary series of WIBP-CorV followed by BBIBP-CorV with a primary series of two doses of BBIBP-CorV. METHODS: We invited healthy 18-59-years-old adults who had already received either WIBP-CorV or BBIBP-CorV as their first dose in a primary series to participate in this observational cohort study. Subjects who had received WIBP-CorV as their first dose became the observation group; subjects who had received BBIBP-CorV as their first dose became the control group. All participants received BBIBP-CorV as their second dose. We obtained sera 1, 2, and 6 months after second doses for nAb titer measurement by micro-neutralization cytopathic effect assay with SARS-CoV-2 strain HB01, standardized with WHO International Standard for anti-SARS-CoV-2 immunoglobulin. Safety was assessed for the 7 days after administration of second doses. RESULTS: Between March and December 2021, 275 subjects were included in the observation group and 133 in the control group. Neutralizing seropositivity (≥1:4) rates were 98.91 % and 99.25 % at 1 month and 53.16 % and 70.69 % at 6 months. One-month geometric mean titers (GMTs) were 21.33 and 22.45; one-month geometric mean concentrations (GMCs) were 227.71 IU/mL and 273.27 IU/mL. One to two months after vaccination, observation group seropositivity rates and titers were not significantly different to the control group's. Adverse reaction rates were 11.27 % and 18.80 %, all mild or moderate in severity. CONCLUSIONS: Both primary series were immunogenic; immunogenicity of WIBP-CorV followed by BBIBP-CorV was not different than immunogenicity following two doses of BBIBP-CorV for two months after vaccination; safety profiles were acceptable for both regimens. BBIBP-CorV can be used to complete a primary series that started with WIBP-CorV.

Immunogenicity and safety of an enterovirus 71 vaccine in children aged 36-71 months: A double-blind, randomised, similar vaccine-controlled, non-inferiority phase III trial.

Background: The enterovirus 71 (EV71) vaccine produced by Wuhan Institute of Biological Products Co., Ltd. (WIBP) (B-EV71) has been given to children aged 6-35 months, and it has shown good safety, immunogenicity and efficacy. However, the administration of EV71 vaccine in children aged 36-71 months, which is another target population, needs further exploration. Methods: We conducted a double-blind, randomised, controlled, non-inferiority phase III clinical trial in children aged 36-71 months, with a further comparison group of children aged 6-35 months in China. Children aged 6-71 months with no history of hand, foot and mouth disease or prior-vaccination of EV71 vaccine were eligible and recruited. Eligible participants aged 36-71 months were randomly assigned (1:1) to receive two doses of the B-EV71 vaccine (Older-B group) or the control EV71 vaccine (C-EV71 vaccine, produced by Institute of Medical Biology, Chinese Academy of Medical Sciences) (Older-C group), administered at a 30-day interval. Eligible participants aged 6-35 months were enrolled consecutively to receive two doses of the B-EV71 vaccine (Younger-B group) at a 30-day interval. Participants, investigators and those assessing outcomes were masked to the vaccine received. Non-inferiority analyses were conducted to compare the immunogenicity of EV71 vaccine in the Older-B group with that in the Older-C and Younger-B groups. Non-inferiority margins were 10% for seroconversion rate differences and 0.5 for geometric mean titre (GMT) ratios. The primary endpoints were the GMT level and seroconversion rate of anti-EV71 neutralising antibody 30 days after the second dose of vaccination. The primary analysis was performed in the per-protocol population. Safety analyses were conducted amongst participants receiving at least one dose of vaccine. This trial was registered at Chinadrugtrials.org.cn (#CTR20192345). Findings: Between June 3 and June 30, 2020, 1600 participants were enrolled and assigned, including 625 participants in the Older-B group, 625 participants in the Older-C group and 350 participants in the Younger-B group. The seroconversion rate of anti-EV71 neutralising antibody in the Older-B group (99.66%; 95% CI: 99.18%-100.00%) was non-inferior to that of the Older-C (99.32%; 95% CI: 98.65%-99.98%) and Younger-B groups (100.00%; 95% CI: 100.00%-100.00%). The differences in seroconversion rates in the Older-B group to those in the Older-C and Younger-B groups were 0.34% (95%CI: -2.17%-2.86%) and -0.34% (95%CI: -2.78%-2.09%). The GMT of the anti-EV71 neutralising antibody in the Older-B group (693.87) was also non-inferior to that in the Older-C (289.37) and Younger-B groups (634.80). The ratios of GMTs in the Older-B group to those in the Older-C and Younger-B groups were 2.67 (95%CI: 2.00-3.00) and 1.00 (95%CI: 0.75-1.00), respectively. The incidence of any adverse event (AE) related to vaccination was similar amongst the three groups (34/625 [5.44%] in the Older-B group, 32/623 [5.14%] in the Older-C group, and 26/349 [7.45%] in the Younger-B group), with only 2 (0.57%) participants having grade 3 AEs in the Younger-B group. Fifteen (0.94%) participants from these three groups had reported serious AEs (SAEs), all of which were unrelated to vaccines. Interpretation: EV71 vaccine produced by WIBP could extend to be administered to children aged 36-71 months against EV71 infection. However, the persistence of vaccine-induced immunities needs to be further investigated. Funding: Hubei Province's young medical talent program (20191229), Hubei Province's young talent program (2021), Hubei Province's young public health talent program (2021); and the Wuhan Institute of Biological Products Co., Ltd.

Association between two key SNPs on chromosome 12p13 and ischemic stroke in Chinese Han population.

OBJECTIVE: Genome-wide single nucleotide polymorphism (SNP) association studies recently identified two SNPs (rs11833579 and rs12425791) on chromosome 12p13 that are associated with ischemic stroke (IS) in Caucasian or Black persons from America and the Netherlands. Our aim was to determine whether these SNPs were associated with IS in Chinese Han population. METHODS: We used a case-control study involving 648 IS patients and 648 age-matched, sex-matched, and ethnicity-matched non-IS controls from two ethnic populations and determined the genotypes of two polymorphisms by TaqMan SNP genotyping assays to assess any links with IS. RESULTS: Significant allelic association was identified between rs11833579 and IS in the Han population (odds ratio=1.27, 95% confidence interval=1.08-1.49). One risk haplotype (A-G; odds ratio=1.52, 95% confidence interval=1.21-1.92) was identified in the Han population. Genotypic association analysis demonstrated that rs11833579 confers susceptibility to IS only in a recessive model (P=0.004) rather in additive model. However, the association between rs12425791 and IS was insignificant in Chinese Han population. CONCLUSION: The A allele of SNP rs11833579 on chromosome 12p13 may play a role in mediating susceptibility to IS in the Han Chinese population in a recessive model. The A-G haplotype is also significantly associated with higher IS risk in the Han Chinese population. However, larger populations are warranted to validate our findings.