Efficacy and safety of high-dose Xueshuantong injection (lyophilised) in reducing the incidence of major adverse cardiovascular events in patients with unstable angina: a protocol of a randomised, parallel-arm, controlled, double-blind and multicentre clinical trial based on dual antiplatelet therapy.

INTRODUCTION: Unstable angina (UA), referred to as acute coronary syndrome (ACS), causes unexpected chest pain. Xueshuantong injection (lyophilised) (XST) is a traditional Chinese herbal injection having the potential to treat ACS. However, no clinical trial has been performed in this field. This clinical trial aims to examine the efficacy and safety of XST. METHODS AND ANALYSIS: This is a randomised, parallel-arm, controlled, double-blind and multicentre clinical trial. A total of 1200 participants with UA will be enrolled in a 1:1 ratio, with 600 patients included in the XST treatment group and 600 with 1/20th dose in the control group. The efficacy assessment and major adverse cardiovascular events will be observed, and the frequency of angina attack, angina pectoris will be examined at the start and end of the run-in period. All adverse events will be recorded, regardless of the severity, to assess the safety of XST. The baseline characteristics of patients will be summarised and compared using the t test or non-parametric statistical test. Qualitative data will be analysed using the χ2 or Fisher exact tests, Cochran-Mantel-Hasenszel test and Wilcoxon test. ETHICS AND DISSEMINATION: This trial has been approved by the Research Ethics Committee of The First Affiliated Hospital of Guangzhou University of Chinese Medicine, China (approval number: ZYYEC [2017] 0021). Written informed consent will be obtained from all participants. The results of this trial will be disseminated to the public through academic conferences and peer-reviewed journals. TRIAL REGISTRATION: This study was registered on the Chinese Clinical Trial Registry (http://www.chictr.org.cn/) with the ID ChiCTR1800015911.

[Heterogeneity of airway macrophage in different clinical phenotypes of COPD patients with frequent or infrequent exacerbations].

OBJECTIVE: To compare the clinical features and the heterogeneity of macrophages in different clinical phenotypes of chronic obstructive pulmonary disease (COPD) patients with frequent or infrequent exacerbations.
 Methods: Clinical characteristics of eighty COPD patients with chronic bronchitis (CB), emphysema (EM) or asthma-COPD overlap (ACO) phenotypes suffered from acute exacerbation were analyzed. The expressions of CCL3 and CD163 in sputum macrophages were detected by flow cytometry. The expressions of HIF-1α and Cav-1 in sputum macrophages were detected by quantitative PCR (qPCR).
 Results: The age, forced expiratory volume in one second (FEV1)/forced vital capacity (FVC), sputum bacteria positive rate, COPD Assessment Test (CAT) score, and Modified Medical Research Council (mMRC) score between the patients with FE and iFE were significantly different (P<0.05). Compared with iFE patients, the fluorescence intensity of CCL3 in sputum macrophages from patients with FE was significantly lower (P<0.01), while CD163 was significantly increased (P<0.01). Meanwhile, HIF-1α and Cav-1 mRNA levels were also significantly increased (P<0.01). The age, sputum bacteria positive rate, CAT score, and mMRC score between the patients of FE and iFE with CB phenotype were significantly different (P<0.05). Compared with iFE patients, the fluorescence intensity of CCL3 in sputum macrophages from FE patients was slightly decreased (P<0.05), while CD163 was significantly raised (P<0.01). Meanwhile, HIF-1α and Cav-1 mRNA levels were also significantly increased (P<0.01). The age, duration of disease, FEV1/FVC, sputum bacteria positive rate, CAT score, and mMRC score between the patients of FE and iFE with EM phenotype were significantly different (P<0.05). Compared with iFE patients, the fluorescence intensity of CCL3 in sputum macrophages from FE patients was slightly decreased (P>0.05), while CD163 was slightly raised (P>0.05). Meanwhile, HIF-1α levels were slightly elevated (P>0.05), while Cav-1 expression was significantly increased (P<0.01). There were no significant differences in all clinical features between FE and iFE patients with ACO phenotype. The fluorescence intensity of CCL3 in sputum macrophages from patients with FE was significantly lower than that in iFE patients (P<0.01); there was no significant difference in CD163 (P>0.05). At the same time, the expression of HIF-1α (P<0.01) and Cav-1(P<0.05) also increased significantly. There was a significant negative correlation between CCL3 and HIF-1α or Cav-1 in all FE and FE patients with CB phenotype. CD163 was only positively correlated with HIF-1α in those patients and FE patients with EM phenotype. There was a significant negative correlation between CCL3 and HIF-1α in FE patients with ACO phenotype, while CD163 was significantly positively correlated with HIF-1α.
 Conclusion: The clinical features of FE or iFE patients with CB, EM or ACO phenotype are different, and M2 in induced sputum from FE patients are dominant. HIF-1α may play a key role in the polarization process.

Hospitalizations for Influenza-Associated Severe Acute Respiratory Infection, Beijing, China, 2014-2016.

We analyzed surveillance data for 2 sentinel hospitals to estimate the influenza-associated severe acute respiratory infection hospitalization rate in Beijing, China. The rate was 39 and 37 per 100,000 persons during the 2014-15 and 2015-16 influenza seasons, respectively. Rates were highest for children <5 years of age.

Willingness to accept a future influenza A(H7N9) vaccine in Beijing, China.

BACKGROUND: The present study aimed to estimate residents' willingness to accept a future H7N9 vaccine and its determinants in the general adult population in Beijing, China. METHODS: We conducted a multi-stage sampling, cross-sectional survey using self-administered anonymous questionnaires from May to June, in 2014. The main outcome variable was residents' willingness to accept a future H7N9 vaccine. Logistic regression was used to identify the predictors of vaccination willingness. RESULTS: Of the 7264 eligible participants, 14.5% of Beijing residents reported that they had not heard of H7N9. Among those who had heard of H7N9, 59.5% of the general adult population would be willing to accept a future H7N9 vaccine, and approximately half of them reported 'I am afraid of being infected by H7N9' and 'H7N9 vaccine can prevent infections', and 28.1% reported 'my daily life is affected by H7N9'. The variables that were significantly associated with a higher likelihood of reporting willingness were being younger adults (aged 18-29 years: OR = 1.52, 95% CI: 1.17-1.97; aged 30-39 years: OR = 1.39, 95% CI: 1.08-1.78), being farmers (OR = 1.61; 95% CI: 1.32-1.96), being unemployed people (OR = 1.36; 95% CI: 1.04-1.78), living in suburban areas (OR = 2.18; 95% CI: 1.89-2.51), having ≥2 children in the family (OR = 1.41; 95% CI: 1.03-1.92), perceived risk in China (OR = 1.30; 95% CI: 1.15-1.48), perceived susceptibility to disease (OR = 3.13; 95% CI: 2.73-3.58), perceived negative effect on daily life (OR = 1.32; 95% CI: 1.13-1.55), perceived effectiveness of vaccination (OR = 2.34; 95% CI: 2.07-2.64), and recent uptake of influenza vaccine (OR = 2.26; 95% CI: 1.92-2.66). CONCLUSIONS: A great number of Beijing residents had doubts about the vaccine's effectiveness and were not concerned about disease risk, which were the factors affecting willingness to be vaccinated. Targeted education programs on disease risk as well as vaccine's effectiveness are needed to improve the willingness of vaccination for potential H7N9 pandemic preparedness.

Factors associated with the uptake of seasonal influenza vaccination in older and younger adults: a large, population-based survey in Beijing, China.

OBJECTIVES: The present study aimed to estimate the influenza vaccination coverage rate in Beijing, China, and identify its determinants in older and younger adults. METHODS: A survey was conducted among Chinese adults using a self-administered, anonymous questionnaire in May-June 2015. The main outcome was seasonal influenza vaccination uptake. Multivariate logistic regression models were performed to identify factors associated with uptake. RESULTS: A total of 7106 participants completed the questionnaire. The overall coverage rate was 20.6% (95% CI 19.7% to 21.5%) in the 2014/2015 influenza season. Lower education (older adults: OR 1.6; 95% CI 1.2 to 2.1; younger adults: OR 1.9; 95% CI 1.4 to 2.6), having a chronic illness (older adults: OR 1.9; 95% CI 1.5 to 2.4; younger adults: OR 1.4; 95% CI 1.2 to 1.7) and recommendations from healthcare workers (older adults: OR 5.4; 95% CI 3.9 to 7.4; younger adults: OR 4.5; 95% CI 3.7 to 5.4) were positively associated with uptake; perceived side effects of vaccination had a negative impact (older adults: OR 0.6; 95% CI 0.4 to 0.7; younger adults: OR 0.8; 95% CI 0.7 to 1.0). Perceived susceptibility to influenza (OR 1.5; 95% CI 1.2 to 2.0) and awareness of the free influenza vaccine policy (OR 1.9; 95% CI 1.2 to 2.9) were only associated with vaccine uptake in older adults, while perceived effectiveness of vaccination (OR 2.2; 95% CI 1.7 to 2.8) was only a predictor for younger adults. Older adults were more likely to receive recommendations from healthcare professionals and perceive the severity of seasonal influenza, and less likely to worry about side effects of vaccination. CONCLUSION: The influenza vaccination coverage rate was relatively low in Beijing. Apart from free vaccinations for older adults, age disparity in the rate between older and younger adults (48.7% vs 16.0%) may be explained by differing professional recommendations and public perceptions. Vaccination campaigns targeting increasing professional recommendations and public perceptions should be implemented in the coming years.

Using a community based survey of healthcare seeking behavior to estimate the actual magnitude of influenza among adults in Beijing during 2013-2014 season.

BACKGROUND: Due to a lack of survey of health care seeking behavior for influenza, the actual magnitude of influenza in Beijing of China has not been well described. METHODS: During 2013-2014 influenza season, two cross-sectional household surveys were carried out respectively during the epidemic and non-epidemic season of influenza. A structured survey was undertaken with individuals who were ≥18 years selected by a multistage random sampling method in the study. Health care seeking behaviors were then examined to estimate the actual case number of influenza, using a multiplier model. RESULTS: A total of 14,665 adults were interviewed. 61.9% of ILI cases consulted a physician. The consultation rate during epidemic period is higher than that during non-epidemic period (67.9% vs. 52.3%). Similarly, the proportion of healthcare usage of general hospital during epidemic period is higher than that was during non-epidemic period (27.1% vs. 19.0%, p = 0.008). Lack of insurance and education reduced healthcare seeking significantly in this study. It was estimated that there were 379,767 (90% CI = [281,934, 526,565]) confirmed cases of influenza amongst adults in Beijing, during 2013-2014 influenza season, with an incidence rate of 2.0%. CONCLUSIONS: The surveillance system for ILI and virological data has the potential to provide baseline case number to estimate the actual annual magnitude of influenza. Given the changes in healthcare seeking behavior over time, sentinel surveillance on healthcare seeking behavior are required to be established for better estimate of the true case number of influenza.

Hygiene Behaviors Associated with Influenza-Like Illness among Adults in Beijing, China: A Large, Population-Based Survey.

The objective of this study was to identify possible hygiene behaviors associated with the incidence of ILI among adults in Beijing. In January 2011, we conducted a multi-stage sampling, cross-sectional survey of adults living in Beijing using self-administered anonymous questionnaires. The main outcome variable was self-reported ILI within the past year. Multivariate logistic regression was used to identify factors associated with self-reported ILI. A total of 13003 participants completed the questionnaires. 6068 (46.7%) of all participants reported ILI during the past year. After adjusting for demographic characteristics, the variables significantly associated with a lower likelihood of reporting ILI were regular physical exercise (OR 0.80; 95% CI 0.74-0.87), optimal hand hygiene (OR 0.87; 95% CI 0.80-0.94), face mask use when going to hospitals (OR 0.87; 95% CI 0.80-0.95), and not sharing of towels and handkerchiefs (OR 0.68; 95% CI 0.63-0.73). These results highlight that personal hygiene behaviors were potential preventive factors against the incidence of ILI among adults in Beijing, and future interventions to improve personal hygiene behaviors are needed in Beijing.

Surface antibody and cytokine response to recombinant Chinese hamster ovary cell (CHO) hepatitis B vaccine.

OBJECTIVE: To compare the immune responses of the 10 µg and 20 µg doses of CHO hepatitis B vaccine on adults. METHODS: Adults aged 18-45 years who gave a history of never having received hepatitis B vaccine and lacked serologic evidence of infection to hepatitis B virus (HBV) infection or previous vaccination were enrolled into the study. A total of 642 eligible participants were randomized to receive 3 doses of either the 10 µg or the 20 µg formulation of CHO hepatitis B vaccine in a 0-1-6 month schedule. Each study subject had a serologic specimen collected one month following the third vaccine dose that was tested for markers of HBV infection and anti-HBs by Abbott I2000. Persons who tested negative for anti-HBs negative persons were tested for HBV DNA. Logistic regression was used to identify factors associated with antibody response. Among the participants, 153 subjects had their lymphocytes cultivated and tested for cytokine production. Enzyme-linked immunospot (ELISPOT) was used to test spot numbers of IL-4, IFN-γ which produced by lymphocyte. RESULTS: The anti-HBs seroconversion rate was 88.8% (95% CI: 85.4-92.2%) and 95.3% (95% CI: 93.0-97.6%), respectively in 10 µg and 20 µg group. Geometric mean titers (GMT) were 173.42 mIU/ml and 585.51 mIU/ml, respectively in 10 µg and 20 µg groups. Multivariate analysis demonstrated that diabetes, spouse is hepatitis B virus infector, older age and receipt of the 10 µg dose were all negatively associated with antibody response (P<.05). Cellular immunity results showed: IL-4 immunity spot numbers in 20 µg group was higher than 10 µg group. With anti-HBs increased, the IL-4 immunity spot numbers increased significantly which had significant positive correlation (Spearman coefficient=0.538, P<0.0001). IFN-γ spot numbers had no statistical significant between the two groups. CONCLUSION: The humoral immunity and cytokines response among the group that received the 20 µg CHO hepatitis B vaccine dose was superior compared to the group that received the 10 µg dose. The 20 µg dose of CHO hepatitis B vaccine should be prioritized for adult vaccination programs in China.

[Study on the cellular and humoral immunity effect of recombinant Chinese hamster ovary cell hepatitis B vaccine in adults].

OBJECTIVE: To evaluate the cellular and humoral immunity effect of 10 µg and 20 µg recombinant Chinese hamster ovary (CHO) cell hepatitis B vaccine in adults by randomized double-blind controlled trials. METHOD: A total of 642 adults aged 18 - 45 years old, non-vaccinated against hepatitis B, and hepatitis B five blood indicators negative were selected as the study subjects. The study subjects were randomly divided into two groups and each group had 321 subjects. The subjects were given 10 µg and 20 µg recombinant CHO hepatitis B vaccination respectively by 0, 1st, 6th month schedule. Blood sample was collected from each study subject one month after the second dose vaccination. The anti-HBs level was detected by Abbott chemiluminescence detection method (I2000) to evaluate humoral immunity status. Of all the study objects, 153 cases were randomly selected by the Excel random function. Their blood samples were collected and Lymphocyte were separated to detect the IL-4 and IFN-γ levels in vitro by enzyme-linked immunospot (ELISPOT) method to evaluate the cellular immunity status. RESULTS: The anti-HBs seroconversion rates in 10 µg and 20 µg dose group were 88.8% (285/321) and 95.3% (306/321) respectively, and 95%CI were 85.4% - 92.2% and 93.0% - 97.6% respectively. The spot forming cell (SFC) of IL-4 of the 20 µg-dose group (x(-) = 20.31) were significantly higher than the 10 µg-dose group (x(-) = 8.19, t = 3.27, P < 0.01). With the increasing of anti-HBs titer, the SFC of IL-4 also went up significantly. There was a positive correlation between SFC of IL-4 and anti-HBs (Spearman correlation coefficient = 0.538, P < 0.0001). No significant difference was found for IFN-γ SFC in two groups (10 µg group: x(-) = 1.49; 20 µg group: x(-) = 0.86; t = 1.83, P > 0.05). CONCLUSION: The humoral and cellular immune effects of 20 µg recombinant CHO hepatitis B vaccine are better than that of the 10 µg recombinant CHO hepatitis B vaccine.20 µg recombinant CHO hepatitis B vaccine should be chosen as the adult's hepatitis B prevention vaccine.

[Study on the immuno-effects and influencing factors of Chinese hamster ovary (CHO) cell hepatitis B vaccine among adults, under different dosages].

OBJECTIVE: To evaluate the immuno-effect and related influencing factors on 10 µg and 20 µg Chinese hamster ovary (CHO) cell hepatitis B vaccine, using the randomized double-blind controlled trials in adult population. METHODS: A total of 642 adults aged 18 - 45 years old, non-vaccinated against hepatitis B, and negative on five blood indicators for hepatitis B, were selected as the study objects from four districts in Beijing. The study objects were randomly divided into two groups, and then accepted 10 µg and 20 µg recombinant CHO hepatitis B vaccination by 0 - 1 - 6 month schedule. Influencing factors were investigated by means of questionnaire. Blood samples were collected one month after the third dose of vaccination. Anti-HBs level was detected by Abott chemiluminescence detection method. For the anti-HBs negative person, fluorescent quantitative PCR method was used to find out if the person had been infected with HBV. Logistic regression analysis was used to find out the influencing factors of anti-HBs seroconversion on every studied subject. RESULTS: The anti-HBs seroconversion rates on 10 µg and 20 µg dose groups were 88.8% (95%CI: 85.4% - 92.2%) and 95.3% (95%CI: 93.0% - 97.6%) respectively. Taking the anti-HBs level < 100 mIU/ml as the low/non-response standard, the low response and non-response rates were 34.3% and 17.4% respectively. The geometric mean titers (GMT) of anti-HBs were 173.42 mIU/ml for the 10 µg dose group and 588.51 mIU/ml for the 20 µg dose group. Data from the Multivariate analysis showed that:diabetes, spouses infected with hepatitis B virus and old age were unfavorable factors for anti-HBs Seroconversion. 20 µg dose of the vaccine was conducive to seroconversion. CONCLUSION: 20 µg CHO hepatitis B vaccine seemed better than 10 µg CHO hepatitis B vaccine while many factors need to be taken into account for evaluation on hepatitis B vaccines.

[A sero-epidemiologiecal study on hepatitis B among general population in Beijing].

OBJECTIVE: To explore the serological infection rate of hepatitis B virus (HBV) in general population aged over one year old in Beijing and to provide information for control and prevention of the disease. METHODS: A multistage randomized cluster sampling was carried out in general population of Beijing, aged over one year old. Every study subject's hepatitis B immunization history and main risk factors were investigated through questionnaire. Venous blood samples were collected and then tested for five hepatitis B serological antigens and antibodies by means of Abbott Microparticle Enzyme Immunoassy method. RESULTS: The prevalence rates of HBsAg, anti-HBs, anti-HBc and total HBV infection rate were 3.49% (95% CI:2.99-3.99), 37.79% (95% CI: 36.46-39.12), 35.04% (95% CI: 33.72-36.35) and 35.09% (33.78-36.40) respectively. The age standardized rates were 3.02% ,42.47% ,26.86% and 26.90% respectively. CONCLUSION: Achievement in hepatitis B control and prevention was made in Beijing since the prevalence rate of hepatitis B surface antigen had been below 1% for children aged less than 5 years old. As for the general population, the prevalence rate of hepatitis B surface antigen had reduced to