Genome balance and dosage effect drive allopolyploid formation in Brassica.

Polyploidy is a major evolutionary force that has shaped plant diversity. However, the various pathways toward polyploid formation and interploidy gene flow remain poorly understood. Here, we demonstrated that the immediate progeny of allotriploid AAC Brassica (obtained by crossing allotetraploid Brassica napus and diploid Brassica rapa) was predominantly aneuploids with ploidal levels ranging from near-triploidy to near-hexaploidy, and their chromosome numbers deviated from the theoretical distribution toward increasing chromosome numbers, suggesting that they underwent selection. Karyotype and phenotype analyses showed that aneuploid individuals containing fewer imbalanced chromosomes had higher viability and fertility. Within three generations of self-fertilization, allotriploids mainly developed into near or complete allotetraploids similar to B. napus via gradually increasing chromosome numbers and fertility, suggesting that allotriploids could act as a bridge in polyploid formation, with aneuploids as intermediates. Self-fertilized interploidy hybrids ultimately generated new allopolyploids carrying different chromosome combinations, which may create a reproductive barrier preventing allotetraploidy back to diploidy and promote gene flow from diploids to allotetraploids. These results suggest that the maintenance of a proper genome balance and dosage drove the recurrent conversion of allotriploids to allotetraploids, which may contribute to the formation and evolution of polyploids.

Increasing probability of record-population exposure to high temperature and related health-risks in China.

Combining the comprehensive effects of temperature and humidity, this study applies a heat stress index to project future population exposure to high temperature and related health-risks over China under different climate change scenarios. Results show that the number of high temperature days, population exposure and their related health-risks will increase significantly in the future compared to the reference period (1985-2014), which is mainly caused by the change of >T99p (the wet bulb globe temperature >99th percentile derived from the reference period). The population effect is absolutely dominant in influencing the decrease in exposure to T90-95p (the wet bulb globe temperature is in the range of (90th, 95th]) and T95-99p (the wet bulb globe temperature is in the range of (95th, 99th]), and the climate effect is the most prominent contributor to the upsurge in exposure to > T99p in most areas. An additional 0.1 billion person-days increase in population exposure to T90-95p, T95-99p and >T99p in a given year is associated with the number of deaths by 1002 (95% CI: 570-1434), 2926 (95% CI: 1783-4069) and 2635 (95% CI: 1345-3925), respectively. Compared with the reference period, total exposure to high temperature under the SSP2-4.5 (SSP5-8.5) scenario will increase to 1.92 (2.01) times in the near-term (2021-2050) and 2.16 (2.35) times in the long-term (2071-2100), which will increase the number of people at heat risk by 1.2266 (95% CI: 0.6341-1.8192) [1.3575 (95% CI: 0.6926-2.0223)] and 1.5885 (95% CI: 0.7869-2.3902) [1.8901 (95% CI:0.9230-2.8572)] million, respectively. Significant geographic variations exist in the changes of exposure and related health-risks. The change is greatest in the southwest and south, whereas it is relatively small in the northeast and north. The findings provide several theoretical references for climate change adaptation.

A Systems Vaccinology Approach Reveals Temporal Transcriptomic Changes of Immune Responses to the Yellow Fever 17D Vaccine.

In this study, we used a systems vaccinology approach to identify temporal changes in immune response signatures to the yellow fever (YF)-17D vaccine, with the aim of comprehensively characterizing immune responses associated with protective immunity. We conducted a cohort study in which 21 healthy subjects in China were administered one dose of the YF-17D vaccine; PBMCs were collected at 0 h and then at 4 h and days 1, 2, 3, 5, 7, 14, 28, 84, and 168 postvaccination, and analyzed by transcriptional profiling and immunological assays. At 4 h postvaccination, genes associated with innate cell differentiation and cytokine pathways were dramatically downregulated, whereas receptor genes were upregulated, compared with their baseline levels at 0 h. Immune response pathways were primarily upregulated on days 5 and 7, accompanied by the upregulation of the transcriptional factors JUP, STAT1, and EIF2AK2. We also observed robust activation of innate immunity within 2 d postvaccination and a durable adaptive response, as assessed by transcriptional profiling. Coexpression network analysis indicated that lysosome activity and lymphocyte proliferation were associated with dendritic cell (DC) and CD4+ T cell responses; FGL2, NFAM1, CCR1, and TNFSF13B were involved in these associations. Moreover, individuals who were baseline-seropositive for Abs against another flavivirus exhibited significantly impaired DC, NK cell, and T cell function in response to YF-17D vaccination. Overall, our findings indicate that YF-17D vaccination induces a prompt innate immune response and DC activation, a robust Ag-specific T cell response, and a persistent B cell/memory B cell response.

[Prenatal screening for major fetal heart defects by training sonographers in township hospitals and county health centers: a feasibility study].

OBJECTIVE: To explore the feasibility of screening for major fetal heart disease by training sonographers in township or county level hospitals. METHODS: Training of B ultrasound scan for congenital heart defects was given to the sonographers from one county hospital, and thirteen township hospitals (or the district hospitals), and training of fetal echocardiography was given to sonographers from four city/county hospitals. The trained sonographers who had passed the examinations and had obtained qualifications after six months of independent practice began to screen fetal congenital heart defects. To evaluate the effectiveness, sensitivity and specificity of screening was calculated by using the diagnosis of expert neonatal/fetal echocardiographers as the gold standard. RESULTS: A total of 3 425 fetuses received one fetal B ultrasound screening, one fetal echocardiography and one neonatal echocardiography from April 1, 2004 to December 31, 2005. One hundred and sixty-five B ultrasound screening images (4.9%) from township hospitals and fifty-six fetal echocardiography images (1.7%) from county or city centers couldn't be reviewed because of poor quality. The sensitivity of fetal B ultrasound screening in the township and county hospitals was 30% and 0, and the specificity 93.3% and 99.9%, respectively. Nine fetuses with a major congenital heart disease were eventually found by the trained sonographers, and two cases were misdiagnosed and two unnoticed. The total sensitivity and specificity of fetal echocardiography were 81.8% and 99.9%, respectively. The sensitivity in the county and city hospitals was 66.7% and 100%, respectively. The specificity in the county and city hospitals was 99.9% and 100%, respectively. CONCLUSION: Under the current circumstances, township hospitals are unable to perform effective fetal cardiac screening. Screening on fetal congenital heart disease is suggested to be taken by trained sonographers in county and city level medical centers.

A 60-year review on the changing epidemiology of measles in capital Beijing, China, 1951-2011.

BACKGROUND: China pledged to join the global effort to eliminate measles by 2012. To improve measles control strategy, the epidemic trend and population immunity of measles were investigated in 1951-2011 in Beijing. METHODS: The changing trend of measles since 1951 was described based on measles surveillance data from Beijing Centre of Disease Control and Prevention (CDC). The measles vaccination coverage and antibody level were assessed by routinely reported measles vaccination data and twenty-one sero-epidemiological surveys. RESULTS: The incidence of measles has decreased significantly from 593.5/100,000 in 1951 (peaked at 2721.0/100,000 in 1955), to 0.5/100,000 in 2011 due to increasing vaccination coverage of 95%-99%. Incidence rebounded from 6.6/100,000 to 24.5/100,000 since 2005 and decreased after measles vaccine (MV) supplementary immunization activities (SIAs) in 2010. Measles antibody positive rate was 85%-95% in most of years since 1981. High-risk districts were spotted in Chaoyang, Fengtai and Changping districts in recent 15 years. Age-specific incidence and proportion of measles varied over time. The most affected population were younger children of 1-4 years before 1978, older children of 5-14 years in 1978-1996, infant of <1 years and adults of ≥15 years in period of aim to measles elimination. CONCLUSION: Strategies at different stages had a prevailing effect on the epidemic dynamics of measles in recent 60 years in Beijing. It will be essential to validate reported vaccination coverage, improve vaccination coverage in adults and strengthen measles surveillance in the anticipated elimination campaign for measles.

[Analysis of adverse events following 2009 influenza A (H1N1) vaccinoprophylaxis in Beijing].

OBJECTIVE: To evaluate the safety of 2009 influenza A (H1N1) vaccine based on mass immunization initiative in Beijing. METHOD: There were 2 113 280 people were vaccinated during September to December 2009. The information of adverse events following immunization (AEFI) was collected through surveillance system, and descriptive methodology was used for data analysis. RESULTS: A Total of 612 AEFI cases were reported, among which there were 321 vaccine reaction cases following immunization, 203 coincidental illness cases, 82 psychogenic reaction cases, and 6 pending cases. The rates of rare reactions and common reactions associated with vaccination were respectively 5.54/100 000 (117/2 113 280) and 9.65/100 000 (204/2 113 280). The rate of serious rare reaction was 0.19/100 000 (4/2 113 280). The rates of vaccine reactions in urban, suburb and county were 16.87/100 000 (36/213 519), 17.81/100 000 (187/1 049 817) and 11.53/100 000 (98/849 944), respectively. The rates of rare reaction and common reaction in different age groups were between 3.65/100 000 (6/164 604) to 8.99/100 000 (27/300 176), and between 0.61/100 000 (1/164 604) to 22.06/100 000 (85/385 275). The 117 rear vaccine reaction cases were mainly allergic reaction (107 cases), and the 204 common vaccine reaction cases were mainly fever (176 cases). There were 91.90% (295/321) vaccine reactions occurred within 24 hours of administration, and all cases had improved consequence. CONCLUSION: The mostly symptoms of AEFI cases during the period of 2009 influenza A (H1N1) vaccinoprophylaxis were anaphylaxis and fever. The types of adverse reactions and the level of serious events are consistent with the anticipation. There were no rear or new events occurred.

[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.

Assessing the quality of primary healthcare for diabetes in China: multivariate analysis using the China Health and Retirement Longitudinal Study (CHARLS) Database.

OBJECTIVE: To assess the quality of primary healthcare (PHC) for patients with diabetes in China from 2011 to 2015. SETTING: This study analysed data on 1006, 1472 and 1771 participants with diabetes who were surveyed in 2011, 2013 and 2015, respectively, in the China Health and Retirement Longitudinal Study, a nationally representative survey conducted in 29 provinces of China. OUTCOME MEASURES: The study measured the proportions of patients with diabetes who received diabetes-related health education, examinations and treatments, as well as the hospital admission rate due to diabetes of these patients. Multilevel logistic regression was used to adjust sociodemographic variables. RESULTS: According to the multivariate analysis, the proportion of patients who received diabetes-related health education decreased significantly (OR=0.74, 95% CI 0.61 to 0.90), and the proportion of those receiving examinations and treatments remained unchanged from 2011 to 2015. Diabetes-related hospitalisation increased from 4.01% in 2011 to 6.08% in 2013 (OR=1.47, 95% CI 0.97 to 2.22), and recurrent hospitalisations increased from 18.87% in 2011 to 28.45% in 2015 (OR=1.78, 95% CI 1.44 to 2.20). The proportions of patients with diabetes-related and recurrent hospitalisations in western China were higher than those in the east (OR=1.80, 95% CI 1.13 to 2.87; OR=1.92, 95% CI 1.50 to 2.45). CONCLUSIONS: Nationally, the analysis of patient-reported process and outcome indicators cannot confirm that the quality of PHC has improved in China during 2011-2015. Regional disparities in primary diabetes care require urgent resource allocation to western China. Establishing a national quality registry for PHC, which transparently reports outcomes by region and social-economic position, is essential for countries sharing the challenge of improving both quality and equity of PHC.

The molecular characterization of serogroup C Neisseria meningitidis strains circulating in Beijing.

The aim of this study was to characterize the molecular features of serogroup C Neisseria meningitidis strains circulating in Beijing, China. Twenty out of 23 strains belonged to ST 4821. The causative serosubtype for meningococcal meningitis was P1.12-1,16-8. All of the strains expressed class 3 PorB protein. Among the five pulsed-field gel electrophoresis patterns observed, pattern III predominated.

Laboratory confirmation of a suspicious meningococcal meningitis death case.

A suspicious meningococcal meningitis death case was reported to the Beijing CDC. The blood specimen was analyzed via multi-PCR and MLST. 6 isolates from close contacts were analyzed via PFGE and MLST. According to the results of the above analyses, the cause of this case was identified as a serogroup A Neisseria meningitidis, which, in terms of sequence typing, belonged the ST7 group.

Safety and immunogenicity of two freeze-dried Vero cell rabies vaccines for human use in post-exposure prophylaxis.

To provide basis for human rabies vaccination in China, the safety and immunogenicity of two freeze-dried Vero cell rabies vaccines for human use were assessed. A total of 250 volunteers were enrolled and divided into two groups: volunteers in Group A (n=200) were vaccinated five doses of Speeda Vero cell rabies vaccine manufactured by Liaoning Chengda Biotechnology Co. Ltd. on day 0, 3, 7, 14, 28 after exposure. Volunteers in Group B (n=50) were treated with Verorab Vero cell rabies vaccine manufactured by Sanofi Pasteur on the same schedule. The local and systematic adverse reactions were observed. Serum neutralizing antibody levels of 80 individuals in Group A and 50 individuals in Group B were tested with RFFIT on day 7, 14, 45, 180, 360 after the first dose. The seroconversion rates in Groups A and B were 40.3% and 37.0% on day 7 after the first dose, 95.5% and 97.7% on day 14, 100% and 100% on day 45, 100% and 100% on day 180, 89.1% and 89.5% on day 360 respectively, indicating no significant differences between the two groups. And no significant differences were found between the neutralizing antibody geometric mean titers (GMTs) of the two groups on day 7, 14, 45, 180 and 360 after the first dose, with the GMTs of day 14, 45, 180 and 360 all higher than 0.5IU/ml. Antibody levels of the two groups peaked around 2 weeks after the full vaccination program, followed by a 55% decrease up to day 180 and another 76% decrease up to day 360. Both groups experienced occasions of transient fever, rash, edema, and scleroma after vaccination. Neither group had any severe adverse reactions. It was concluded that both vaccines showed satisfactory safety and immunogenicity. Booster vaccination is recommended following another exposure after six months since the full vaccination program.

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.

Immunization status and risk factors of migrant children in densely populated areas of Beijing, China.

OBJECTIVE: To properly evaluate the immunization status and determine risk factors of migrant children in 23 densely populated towns and townships in Beijing. METHODS: A household cluster sampling survey was implemented and standard face-to-face interviews were conducted with 1820 migrant children aged 12-35 months. Demographic characteristics of the child and primary caregiver, the child's migrant characteristics, the primary caregiver's knowledge and attitude toward immunization, information about immunization services provided by the local clinic, and the child's immunization history were obtained. Weighted up-to-date (UTD) and age-appropriate immunization rates for the following four vaccines were assessed: three doses of diphtheria, tetanus and pertussis combined vaccine (DTP); three doses of oral poliomyelitis vaccine (OPV); three doses of hepatitis B vaccine (HepB); and one dose of Measles-containing vaccine (MCV). Weighted UTD and age-appropriate immunization rates for the overall series of these four vaccines (the 3:3:3:1 immunization series) were also estimated. Risk factors for not being UTD, being invalid and being delayed for the 3:3:3:1 immunization series were explored using both single-level and multi-level multinomial logistic regression models. RESULTS: For each antigen, the weighted UTD immunization rate was above 83%, but the age-appropriate immunization coverages for HepB, OPV, DPT, and MCV were only 45.6%, 49.6%, 50.8% and 54.7%, respectively. The 1st dose was most likely to be invalid or delayed within HepB, OPV and DPT series. For the 3:3:3:1 immunization series, the weighted UTD and age-appropriate immunization rates were 78.1% and 20.5%, respectively. Immunization status of migrant children tended to be homogenous within a village and therefore, multi-level model was more appropriate for assessing risk factors. Besides demographic characteristics, several other factors were significantly associated with age-appropriate immunization coverage. These factors included: the child's migrant characteristics; the primary caregiver's awareness of the importance of vaccination, and outreach services provided by immunization clinics including notification services and supplementary immunization activities (SIAs). The frequency and duration of clinical immunization sessions significantly influenced the UTD immunization rate but not the age-appropriate immunization rate. The degree of the primary caregiver's satisfaction with clinic services and convenience to vaccination clinic had no impact on the child's immunization status. CONCLUSION: Alarmingly low age-appropriate immunization coverage of migrant children in densely populated areas demanded immediate intervention. Community context was an important factor to a migrant child's vaccination status and should be considered when taking measures. Strategies to strengthen outreach immunization service need to be developed to effectively improve the age-appropriate immunization coverage of migrant children.

[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.

[Effectiveness on post-exposure vaccination of varicella and its influencing factors in elementary schools in Beijing].

OBJECTIVE: To evaluate the effectiveness of post-exposure varicella vaccination in elementary schools in Beijing and to explore its influencing factors. METHODS: From May to July 2007, varicella cases from 49 elementary schools in 4 districts in Beijing were observed prospectively. The study included 7882 children who were from the same classrooms, same floor or same bungalow areas with the varicella cases. Vaccination status, history on varicella and onset of rashes were collected to calculate the secondary attack rate among those children under observation and then the effectiveness of vaccine was calculated. RESULTS: The protection rate on post-exposure vaccination among children under observation was 85.26%. The rates were higher when the 1st case had received varicella vaccine before the onset, vaccines were administered soon after the exposure or there were less varicella cases occurred in the schools. For children in the same class, same floor or bungalow with varicella cases before post-exposure vaccination, the average rates of protection by vaccination were 84.26% and 87.06%, respectively. When the 1st case had received varicella vaccine prior to the onset, the post-exposure protection rates reached 92.09% and 93.06%, respectively, higher than that of the case when the 1st case had received no vaccination. When the administration of vaccine right after the occurrence of first varicella case, the rates of the effectiveness of vaccine were 83.09% and 93.02%, both of which were higher than that of vaccine administered after the occurrence of 2 or 3 cases. When the vaccine administration of vaccination combined with the isolation of the already infected cases or within 5 days after the onset of the 1st case, the vaccine effectiveness could reach 86.60% and 92.73%, both were higher than otherwise. However, in those schools that bungalows were used as classrooms but without bus, canteen from school or student lodgings, it seemed that post exposure vaccination was more effective in preventing varicella from occurring. CONCLUSION: Varicella vaccination after exposure in elementary schools in Beijing was effective in prevention and control of the disease. Immediate administration together with the isolation of cases could maximize the effectiveness of the vaccine.