HIV-1 drug resistance and genetic transmission network among newly diagnosed people living with HIV/AIDS in Ningbo, China between 2018 and 2021.

BACKGROUND: As the HIV epidemic continues to grow, transmitted drug resistance(TDR) and determining relationship of HIV transmission are major barriers to reduce the risk of HIV transmissions.This study aimed to examine the molecular epidemiology and TDR and evaluated the transmission pattern among newly diagnosed people living with HIV/AIDS(PLWHA) in Ningbo city, which could contribute to the development of targeted precision interventions. METHODS: Consecutive cross-sectional surveys were conducted in Ningbo City between January 2018 and December 2021. The HIV-1 pol gene region was amplified and sequenced for drug resistance and genetic transmission network analysis. TDR was determined using the Stanford University HIV Drug Resistance Database. Genetic transmission network was visualized using Cytoscape with the genetic distance threshold of 0.013. RESULTS: A total of 1006 sequences were sequenced successfully, of which 61 (6.1%) showed evidence of TDR. The most common mutations were K103N (2.3%), E138A/G/Q (1.7%) and V179D/E (1.2%). 12 HIV-1 genotypes were identified, with CRF07_BC being the major genotype (43.3%, 332/767), followed by CRF01_AE (33.7%, 339/1006). 444 (44.1%) pol sequences formed 856 links within 120 transmission clusters in the network. An increasing trend in clustering rate between 2018 and 2021(χ2 = 9.546, P = 0.023) was observed. The odds of older age (≥ 60 years:OR = 2.038, 95%CI = 1.072 ~ 3.872, compared to < 25 years), HIV-1 genotypes (CRF07_BC: OR = 2.147, 95%CI = 1.582 ~ 2.914; CRF55_01B:OR = 2.217, 95%CI = 1.201 ~ 4.091, compared to CRF01_AE) were significantly related to clustering. Compared with CRF01_AE, CRF07_BC were prone to form larger clusters. The largest cluster with CRF07_BC was increased from 15 cases in 2018 to 83 cases in 2021. CONCLUSIONS: This study revealed distribution of HIV-1 genotypes, and genetic transmission network were diverse and complex in Ningbo city. The prevalence of TDR was moderate, and NVP and EFV were high-level NNRTI resistance. Individuals aged ≥ 60 years old were more easily detected in the networks and CRF07_BC were prone to form rapid growth and larger clusters. These date suggested that surveillance and comprehensive intervention should be designed for key rapid growth clusters to reduce the potential risk factors of HIV-1 transmission.

Vaccination coverage estimates and utilization patterns of inactivated enterovirus 71 vaccine post vaccine introduction in Ningbo, China.

BACKGROUND: In China, enterovirus 71 (EV71) is the major etiological agents of hand foot mouth disease that poses severe risks to children's health. Since 2015, three inactivated EV71 vaccines have been approved for use. Previous studies indicated the high willingness of EV71 vaccination in eastern China. However, few studies have assessed coverage and utilization patterns of EV71 vaccine in China. METHODS: Children born during 2012-2018 were sampled and their records were abstracted from Ningbo childhood immunization information management system. Descriptive statistics characterized the study population and assessed coverage and timeliness for EV71 vaccination. Simultaneous administration patterns as well as type of EV71 vaccine used were also evaluated. Bivariate and multivariable analysis was used to examine the relationship of socio-demographic characteristics with vaccination coverage and timeliness. RESULTS: Of 716,178 children living in Ningbo. One hundred seventy-two thousand two hundred thirty-six received EV71 vaccine with a coverage rate of 24.05% and only 8.61% received vaccination timely. 21.97% of children received the complete two dose EV71 series but only 6.49% completed timely. Vaccination coverage and timeliness increased significantly from 2012 birth cohort to 2018 birth cohort. Relatively higher coverage and timeliness were observed in resident children, Inner districts, high socioeconomic areas and large-scaled immunization clinics. Of 329,569 doses of EV71 vaccine, only 5853(1.78%) doses were administered at the same day as other vaccines. CONCLUSIONS: There is a need for increasing EV71 vaccination coverage and timeliness as well as eliminating disparities among different populations. Our study highlights the importance of simultaneous administration to increasing coverage and timeliness of EV71 vaccination.

5,5-Difluoro- and 5-Fluoro-5-methyl-hexose-based C-Glucosides as potent and orally bioavailable SGLT1 and SGLT2 dual inhibitors.

(2S,3R,4R,5S,6R)-2-Aryl-5,5-difluoro-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4-diols and (2S,3R,4R,5S,6R)-2-aryl-5-fluoro-5-methyl-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4-diols were discovered as dual inhibitors of sodium glucose co-transporter proteins (e.g. SGLT1 and SGLT2) through rational drug design, efficient synthesis, and in vitro and in vivo evaluation. Compound 6g demonstrated potent dual inhibitory activities (IC50 = 96 nM for SGLT1 and IC50 = 1.3 nM for SGLT2). It showed robust inhibition of blood glucose excursion in an oral glucose tolerance test (OGTT) in Sprague Dawley (SD) rats when dosed at both 1 mg/kg and 10 mg/kg orally. It also demonstrated postprandial glucose control in db/db mice when dosed orally at 10 mg/kg.

Hit-to-lead optimization and discovery of a potent, and orally bioavailable G protein coupled receptor kinase 2 (GRK2) inhibitor.

G-protein coupled receptor kinase 2 (GRK2), which is upregulated in the failing heart, appears to play a critical role in heart failure (HF) progression in part because enhanced GRK2 activity promotes dysfunction of ß-adrenergic signaling and myocyte death. An orally bioavailable GRK2 inhibitor could offer unique therapeutic outcomes that cannot be attained by current heart failure treatments that directly target GPCRs or angiotensin-converting enzyme. Herein, we describe the discovery of a potent, selective, and orally bioavailable GRK2 inhibitor, 8h, through high-throughput screening, hit-to-lead optimization, structure-based design, molecular modelling, synthesis, and biological evaluation. In the cellular target engagement assays, 8h enhances isoproterenol-mediated cyclic adenosine 3',5'-monophosphate (cAMP) production in HEK293 cells overexpressing GRK2. Compound 8h was further evaluated in a human stem cell-derived cardiomyocyte (HSC-CM) contractility assay and potentiated isoproterenol-induced beating rate in HSC-CMs.

Associations between ambient air pollution and daily incidence of pediatric hand, foot and mouth disease in Ningbo, 2014-2016: a distributed lag nonlinear model.

Hand, foot and mouth disease (HFMD) has high prevalence around the world, with serious consequences for children. Due to the long survival period of HFMD virus in ambient air, air pollutants may play a critical role in HFMD epidemics. We collected data on daily cases of HFMD among children aged 0-14 years in Ningbo City between 2014 and 2016. Distributed lag nonlinear models were used to assess the effects of particulate matter (PM2.5), sulphur dioxide (SO2), nitrogen dioxide (NO2) and ozone (O3) on the daily incidence of HFMD among children, with analyses stratified by gender and age. Compared with moderate levels of air pollution, high SO2 levels had a relative risk (RR) of 2.32 (95% CI 1.42-3.79) and high NO2 levels had a RR of 2.01 (95% CI 1.22-3.31). The RR of O3 was 2.12 (95% CI 1.47-3.05) and that of PM2.5 was 0.77 (95% CI 0.64-0.92) at moderate levels of air pollution. Specifically, high levels of SO2 and NO2 had RRs of 2.39 (95% CI 1.44-3.96) and 2.02 (95% CI 1.21-3.39), respectively, among 0-4-year-old children, while high O3 had an RR of 2.31 (95% CI 1.09-4.89) among 5-14-year-old children. Our findings suggest significant associations of high SO2 and NO2 levels and moderate O3 levels in HFMD epidemics, and also indicate that air pollution causes lagged effects on HFMD epidemics. Our study provides practical and useful data for targeted prevention and control of HMFD based on environmental evidence.

Active Surveillance of Adverse Events Following Human Papillomavirus Vaccination: Feasibility Pilot Study Based on the Regional Health Care Information Platform in the City of Ningbo, China.

BACKGROUND: Comprehensive safety data for vaccines from post-licensure surveillance, especially active surveillance, could guide administrations and individuals to make reasonable decisions on vaccination. Therefore, we designed a pilot study to assess the capability of a regional health care information platform to actively monitor the safety of a newly licensed vaccine. OBJECTIVE: This study aimed to conduct active surveillance of human papillomavirus (HPV) vaccine safety based on this information platform. METHODS: In 2017, one of China's most mature information platforms with superior data linkage was selected. A structured questionnaire and open-ended interview guidelines were developed to investigate the feasibility of active surveillance following HPV vaccination using the regional health care information platform in Ningbo. The questionnaire was sent to participants via email, and a face-to-face interview was conducted to confirm details or resolve discrepancies. RESULTS: Five databases that could be considered essential to active surveillance of vaccine safety were integrated into the platform starting in 2015. Except for residents' health records, which had a coverage rate of 87%, the data sources covered more than 95% of the records that were documented in Ningbo. All the data could be inherently linked using the national identity card. There were 19,328 women who received the HPV vaccine, and 37,988 doses were administered in 2017 and 2018. Women aged 30-40 years accounted for the largest proportion. Quadrivalent vaccination accounted for 73.1% of total vaccination, a much higher proportion than that of bivalent vaccination. Of the first doses, 60 (60/19,328, 0.31%) occurred outside Ningbo. There were no missing data for vaccination-relevant variables, such as identity card, vaccine name, vaccination doses, vaccination date, and manufacturer. ICD-10 coding could be used to identify 9,180 cases using a predefined list of the outcomes of interest, and 1.88% of these cases were missing the identity card. During the 90 days following HPV vaccination, 4 incident cases were found through the linked vaccination history and electronic medical records. The combined incident rate of rheumatoid arthritis, optic neuritis, and Henoch-Schonlein purpura was 8.84/100,000 doses of bivalent HPV, and the incidence rate of rheumatoid arthritis was 3.75/100,000 doses of quadrivalent HPV. CONCLUSIONS: This study presents an available approach to initiate an active surveillance system for adverse events following HPV vaccination, based on a regional health care information platform in China. An extended observation period or the inclusion of additional functional sites is warranted to conduct future hypothesis-generating and hypothesis-confirming studies for vaccine safety concerns.

Discovery of potent and orally bioavailable indazole-based glucagon receptor antagonists for the treatment of type 2 diabetes.

Type 2 diabetes mellitus (T2DM) is characterized by chronically elevated plasma glucose levels. The inhibition of glucagon-induced hepatic glucose output via antagonism of the glucagon receptor (GCGR) using a small-molecule antagonist is a promising mechanism for improving glycemic control in the diabetic state. The present work discloses the discovery of indazole-based ß-alanine derivatives as potent GCGR antagonists through an efficient enantioselective synthesis and structure-activity relationship (SAR) exploration and optimization. Compounds within this class exhibited excellent pharmacokinetic properties in multiple preclinical species. In an acute dog glucagon challenge test, compound 13K significantly inhibited glucagon-mediated blood glucose increase when dosed orally at 10 mg/kg.

Design, synthesis and structure activity relationships of indazole and indole derivatives as potent glucagon receptor antagonists.

A novel series of indazole/indole derivatives were discovered as glucagon receptor (GCGR) antagonists through scaffold hopping based on two literature leads: MK-0893 and LY-2409021. Further structure-activity relationship (SAR) exploration and optimization led to the discovery of multiple potent GCGR antagonists with excellent pharmacokinetic properties in mice and rats, including low systemic clearance, long elimination half-life, and good oral bioavailability. These potent GCGR antagonists could be used for potential treatment of type II diabetes.

Design, synthesis and biological evaluation of (2S,3R,4R,5S,6R)-5-fluoro-6-(hydroxymethyl)-2-aryltetrahydro-2H-pyran-3,4-diols as potent and orally active SGLT dual inhibitors.

A new series of (2S,3R,4R,5S,6R)-5-fluoro-6-(hydroxymethyl)-2-aryltetrahydro-2H-pyran-3,4-diols as dual inhibitors of sodium glucose co-transporter proteins (SGLTs) were disclosed. Two methods were developed to efficiently synthesize C5-fluoro-lactones 3 and 4, which are key intermediates to the C5-fluoro-hexose based C-aryl glucosides. Compound 2b demonstrated potent hSGLT1 and hSGLT2 inhibition (IC50 = 43 nM for SGLT1 and IC50 = 9 nM for SGLT2). It showed robust inhibition of blood glucose excursion in oral glucose tolerance test (OGTT) in Sprague Dawley (SD) rats and exerted pronounced antihyperglycemic effects in db/db mice and high-fat diet-fed ZDF rats when dosed orally at 10 mg/kg.

Synthesis and biological evaluation of benzocyclobutane-C-glycosides as potent and orally active SGLT1/SGLT2 dual inhibitors.

Synthesis and biological evaluation of benzocyclobutane-C-glycosides as potent and orally active SGLT1/SGLT2 dual inhibitors are described. Compound 19 showed high inhibitory potency at SGLT1 (IC50 = 45 nM), and excellent potency at SGLT2 (IC50 = 1 nM). It also displayed excellent PK profiles in mice, rats, dogs and monkeys (F = 78-107%). In SD rats, compound 19 treatments significantly reduced blood glucose levels in a dose-dependent manner. In ZDF rats, compound 19 displayed anti-hyperglycemic effect up to 24 h. Therefore, compound 19 may serve as valuable pharmacological tool, and potential use as a treatment for metabolic syndrome.

The burden of ischemic heart disease related to ambient air pollution exposure in a coastal city in South China.

OBJECTIVE: Air pollution is considered one of the most important risk factors for ischemic heart disease (IHD), which is a major public health concern. The disease burden of IHD has continued to rise in China in the past two decades. However, epidemiological studies examining the associations between air pollution and IHD have been scarce in China, and the only studies were conducted in severe air pollution areas, where air pollution levels seriously exceed the World Health Organization Air Quality Guidelines. Whether the influence of air pollution on IHD in areas with relatively low levels of air pollution differs from the influence of high pollution levels in heavily studied areas was unknown until now. Furthermore, the estimation of the disease burden of IHD related to air pollution has been very limited. METHODS: We conducted a time-series study to estimate the short-term burden of ambient air pollution on IHD using the indicator of years of life lost (YLL), based on 10 322 IHD deaths from 2011 to 2015 in Ningbo, a coastal city in South China. RESULTS: The mean concentrations of fine particle (PM2.5), sulfur dioxide (SO2) and nitrogen dioxide (NO2) were 49.58 µg/m3, 21.34 µg/m3 and 43.41 µg/m3, respectively. A 10 µg/m3 increase in PM2.5, SO2 and NO2 was associated with changes in YLL of 0.71 (95%CI: - 0.21,1.64), 3.31 (95%CI: 0.78, 5.84), and 2.27 (95%CI: 0.26, 4.28) years, respectively. Relatively stronger impacts were found for gaseous pollutants than PM2.5. A larger increase in YLL was found in the younger population than in the older population for NO2 exposure. In addition, estimations of the effects of SO2 and NO2 on YLL were higher for males than females. SO2 exposure was positively associated with YLL in widowed group. CONCLUSIONS: The findings highlighted the importance of stringent air pollution control, especially for gaseous pollutants. Furthermore, using the indicator of YLL, considering the occurrence of death at different ages, provided more information for resource allocation and protection of vulnerable populations.

Projections for temperature-related years of life lost from cardiovascular diseases in the elderly in a Chinese city with typical subtropical climate.

OBJECTIVE: Extreme temperature is an important risk factor for cardiovascular diseases, and the elderly are particularly vulnerable to temperature variation. Global warming and the increasingly aging population are two major global challenges for human health; thus, an urgent need exists to project the temperature-related cardiovascular disease burden regarding both of the aforementioned factors. We aimed to the project temperature-related burden of cardiovascular diseases using years of life lost (YLL) in the elderly in a Chinese city with typical subtropical climate. METHODS: A retrospective time-series study was first conducted to estimate cardiovascular disease burden associated with temperature in the elderly from 2008 to 2015 in Ningbo, China. Then, future projections considering demographic change and adaptation under 19 global-scale climate models (GCMs) and 3 different Representative Concentration Pathways (RCPs) scenarios for the 2050s and 2070s were estimated. RESULTS: The exposure-response curve for temperature on YLL from cardiovascular diseases was U-shaped, with increased YLL for both higher- and lower- than optimal temperature. The projected annual increase in heat-related YLL was outweighed by the decrease in cold-related YLL. However, monthly analysis demonstrated that temperature-related YLL will increase significantly in August. Additionally, heat-related YLL is projected to increase 3.1-11.5 times for the 2050s and 2070s relative to baseline, when considering demographic changes, even with 30% adaptation taken into consideration. CONCLUSIONS: Although annual YLL from cardiovascular diseases in the elderly associated with temperature will decrease in the future, heat-related YLL will increase tremendously, which indicates that more adaptation strategies and greenhouse emission control measures should be undertaken to reduce the future heat-related burden of cardiovascular diseases in the elderly.

The short term burden of ambient fine particulate matter on chronic obstructive pulmonary disease in Ningbo, China.

BACKGROUND: Numerous studies have found associations between ambient fine particulate matter (PM2.5) and increased mortality risk. However, little evidence is available on associations between PM2.5 and years of life lost (YLL). We aimed to estimate the YLL due to chronic obstructive pulmonary disease (COPD) mortality related to ambient PM2.5 exposure. METHODS: A time-series study was conducted based on the data on air pollutants, meteorological conditions and 18,472 registered COPD deaths in Ningbo, China, 2011-2015. The effects of PM2.5 on YLL and daily death of COPD were estimated, after controlling long term trend, meteorological index and other confounders. RESULTS: The impact of PM2.5 on YLL due to COPD lasted for 5 days (lag 0-4). Per 10 µg/m3 increase in PM2.5 was associated with 0.91 (95%CI: 0.16, 1.66) years increase in YLL. The excess YLL of COPD mortality were 8206 years, and 0.38 day per person in Ningbo from 2011 to 2015. The exposure-response curve of PM2.5 and YLL due to COPD showed a non-linear pattern, with relatively steep at low levels and flattened out at higher exposures.. Furthermore, the effects were significantly higher in the elderly than those in the younger. CONCLUSIONS: Our findings explored burden of PM2.5 on YLL due to COPD and highlight the importance and urgency of ambient PM2.5 pollution control and protection of the vulnerable populations.

A randomized controlled trial to evaluate the impact of a geo-specific poster compared to a general poster for effecting change in perceived threat and intention to avoid drowning 'hotspots' among children of migrant workers: evidence from Ningbo, China.

BACKGROUND: Drowning among children of migrant workers is a major, though neglected public health issue in China. METHODS: A randomised controlled trial was used to examine the potential impact of viewing a preventive health poster with/without geo-located drowning events on perceptions of drowning risk among Chinese migrant children. A total of 752 children from three schools in Jiangbei district were selected by multi-stage sampling and randomly assigned to the intervention (n = 380) or control (n = 372). Multilevel models were used to analyse changes in responses to the following questions after viewing the assigned poster for 10 min: (1) "Do you believe that drowning is a serious health problem in Ningbo city?"; (2) "Do you believe that there are lots of drowning-risk waters around you?"; (3) "Do you believe that the likelihood of your accessing a drowning-risk water is great?"; and (4) "Would you intend to avoid accessing to those drowning-risk waters when being exposed?" RESULTS: At baseline there were no significant differences between the intervention and control groups in perceptions of drowning risk or covariates. Following the intervention, participants that viewed the geo-specific poster were more likely to respond more favourably to the first three questions (p < 0.001) than those who viewed the standard poster. However, there was no substantive difference between the geo-specific or standard poster in terms of changing intentions to avoid drowning hotspots (p = 0.214). CONCLUSIONS: Use of 'geo-located' information added value to the effectiveness of a drowning prevention poster for enhancing awareness of drowning hotspots among children of migrant workers. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-IOR-16008979 (Retrospectively registered) (The date of trial registration: Aug 5, 2016, the date of enrolment of the first participant: Nov 10, 2015).

Knowledge and perceptions of air pollution in Ningbo, China.

BACKGROUND: The residents' knowledge, attitudes and practices related to ambient air pollution and health will help to improve the understanding of environmental protection and make environmental health policies more targeted and effective. This study aimed at knowing the attitudes and behaviors towards ambient air pollution and health. METHODS: A cross-sectional survey was conducted in Ningbo, China in January 2015. Personal information and questions pertaining to the knowledge, attitudes and practices towards ambient air pollution and health were collected through questionnaire investigations. Descriptive statistics, chi-square tests and multiple unconditional logistic regression analysis were used. RESULTS: The questionnaire was completed by 1604 respondents (59.41 % women). The awareness rate was 64.59 % and varied significantly with age, levels of education, and occupation (all p < 0.05). Only 5.80 % of the total participants were satisfied with the air quality in Ningbo in 2014. Most respondents (78.80 %) expressed concern about the possible aggravation of the haze. More than 80 % of participants believed that it will take at least 3-5 years or longer before the air quality is improved. Television and internet resources have replaced books and newspapers as the primary sources for obtaining knowledge about haze and related protective measures. 85.22 % of respondents were concerned about air quality index (AQI). Most of the residents have taken protective measures indoors during haze weather. 48.50 % have worn face masks when going outside, the most frequently type of face masks selected were cotton (39.85 %) or gauze face masks (36.24 %). Age and occupation were the main factors associated with the level of knowledge about air pollution (p < 0.05). CONCLUSIONS: There were a relatively high knowledge awareness rate, strong health protection consciousness and high enthusiasm for air pollution control among Ningbo residents. The elderly people and less-educated residents are the targetable population for improving environment.

N-3 polyunsaturated fatty acids intake and risk of colorectal cancer: meta-analysis of prospective studies.

BACKGROUND: Growing body of laboratory evidence supports the beneficial effects of n-3 polyunsaturated fatty acids (PUFAs) on colorectal cancer (CRC) prevention. Epidemiologic studies investigating the relationship between n-3 PUFAs intake and risk of CRC, however, have been inconsistent. We aimed to clarify the relation by conducting a meta-analysis of prospective studies. METHODS: Eligible studies were identified by searching PubMed database and by carefully reviewing bibliographies of retrieved publications. Summary relative risks (RRs) with their 95 % confidence intervals (CIs) were computed with a random-effects model. Subgroup, meta-regression, and dose-response analyses were performed to explore potential sources of heterogeneity. RESULTS: A total of 14 prospective studies involving 8,775 cancer cases were included in the final analysis. Overall, total n-3 or marine PUFAs intake was not associated with risk of CRC (RR 0.99 and 1.00). However, there was a trend toward reduced risk of proximal colon cancer (total n-3 PUFAs: RR 0.83, 95 % CI 0.66-1.05; marine PUFAs: RR 0.81, 95 % CI 0.59-1.10) and a significant increased risk of distal colon cancer (total n-3 PUFAs: RR 1.26, 95 % CI 1.06-1.50; marine PUFAs: RR 1.38, 95 % CI 1.11-1.71). Furthermore, marine PUFAs intake accessed longer before diagnosis was associated 21 % reduced risk of CRC (RR 0.79, 95 % CI 0.63-1.00). CONCLUSION: Overall, this meta-analysis finds no relation between n-3 PUFAs intake and risk of CRC. The observed subsite heterogeneity within colon cancer and the possible effect modification by latency time merit further studies.

EPIDEMIOLOGY AND RISK FACTORS FOR NONFATAL DROWNING IN THE MIGRANT CHILDREN.

The purpose of this study was to determine the incidence and potential risk factors for nonfatal drowning among migrant workers' children in China. We conducted a cross-sectional survey of students from third to ninth grade at five Migrant Workers' Children schools in Ningbo, China in 2014. General information and a history of nonfatal drowning was obtained from self-reported questionnaires by migrant students. A multivariate logistic regression model was used to identify potential risk factors. A total 3,859 students were included in the current study. Of these, 13.4% had experienced a nonfatal drowning accident (15.2% for males, 11.2% for females). Most nonfatal drowning occurred in natural water settings. Diving into unknown water without adult supervision had the greatest association with history of nonfatal drowning [odds ratio (OR) = 1.97; 95% confidential interval (CI): 1.31-2.95], followed by fishing in water (OR = 1.50; 95% CI: 1.05-2.14), swimming or playing in water (OR = 1.47; 95% CI: 1.02-2.12), and trying to rescue peers in the water if they were drowning (OR = 1.31; 95% CI: 1.04-1.64). There were factors associated with a lower risk of drowing: having a parent accompany the child to school (OR = 0.69; 95% CI: 0.51-0.93),understanding the the danger of swimming alone (OR = 0.69; 95% CI: 0.48-0.99) and having a knowledge about water safety (OR = 0.98; 95% CI: 0.98-0.99). The study population was at inceased risk for nonfatal drowning. Preventive measures, such as improved water-safety knowledge, decreasing risky water-related activities and better supervision of children need to be developed and tested to decrease the risk of nonfatal drowning among the study population.

[Varicella breakthrough infection and vaccine effectiveness with 1-dose varicella].

OBJECTIVE: To evaluate the breakthrough varicella infection rate and varicella vaccine effectiveness (VE) among children who received 1-dose varicella vaccine. METHODS: A total of 57 180 subjects for the consecutive 4-year birth cohorts were selected from the local children born between 2007 and 2010 in Yinzhou District, Ninghai County and Yuyao City. And they were followed up for varicella from 2008 to 2013. The recipients of the vaccinations were identified through Ningbo Immunization Information System and data on breakthrough infections among the recipients were collected by using China Information System for Disease Control and Prevention. The breakthrough varicella rate and the VE were calculated and the trends of them were described from 2008 to 2013 among 4-year birth cohorts. The cumulative incidence of varicella was compared between vaccinated and unvaccinated children among the consecutive 4-year birth cohorts. RESULTS: The rate of varicella vaccine coverage, vaccine cumulative incidence among the cohorts was 96.74% (55 317/57 180) and 0.56% (321/57 180). The breakthrough varicella infection for 4-year birth cohorts was 0.44% (244/55 317), and for each birth cohort was 0.95% (142/14 928), 0.44% (61/13 855), 0.22% (29/13 433) and 0.09% (12/13 101), respectively. It was on the rise from 2008 to 2013 and the 2007 birth cohort of it increased fastest from 0.04% (6/14 928) in 2007 to 0.32% (48/14 834) in 2013. The vaccine cumulative incidence of these who vaccinated 1-dose varicella (the breakthrough varicella infection) was lower than these who were unvaccinated (the incidence: 6.25% (37/592), 3.52% (15/426), 3.69% (17/461) and 2.08% (8/384)) by each birth cohort (χ²= 130.27, P < 0.001 for 2007 birth cohort; χ²= 74.11, P < 0.001 for 2008 birth cohort; χ²= 162.80, P < 0.001 for 2009 birth cohort; χ²= 100.01, P < 0.001 for 2010 birth cohort). The vaccine effectiveness for 4-year birth cohorts was 89.33% (95% CI: 86.7%-92.1%) and for each birth corhort was 84.78% (95% CI: 77.94%-89.50%), 86.82% (95% CI: 77.82%-92.95%), 93.99% (95% CI: 89.27%-96.81%) and 95.60% (95% CI: 89.18%-98.21%), respectively. The effectiveness of each birth cohort declinedgradually from 2008 to 2013 and the 2009 birth cohort of it decreased fastest from 98.86% in 2010 to 66.83% in 2013. CONCLUSIONS: The 1-dose varicella vaccine effectiveness was good, but breakthrough varicella infection rate was on the rise with time and the VE declined gradually from 2008 to 2013.

[Relationship between sulfur dioxide pollution and upper respiratory outpatients in Jiangbei, Ningbo].

OBJECTIVE: To describe the daily average concentration of sulfur dioxide (SO2) in Ningbo, and to analysis the health impacts it caused in upper respiratory disease. METHODS: With outpatients log and air pollutants monitoring data matched in 2011-2013, the distributed lag non-linear models were used to analysis the relative risk of the number of upper respiratory patients associated with SO2, and also excessive risk, and the inferred number of patients due to SO2 pollution. RESULTS: The daily average concentration of SO2 didn't exceed the limit value of second class area. The coefficient of upper respiratory outpatient number and daily average concentration of SO2 matched was 0.44,with the excessive risk was 10% to 18%, the lag of most SO2 concentrations was 4 to 6 days. It could be estimated that about 30% of total upper respiratory outpatients were caused by SO2 pollution. CONCLUSION: Although the daily average concentration of SO2 didn't exceed the standard in 3 years, the health impacts still be caused with lag effect.

The effects of summer temperature and heat waves on heat-related illness in a coastal city of China, 2011-2013.

BACKGROUND: Devastating health effects from recent heat waves in China have highlighted the importance of understanding health consequences from extreme heat stress. Despite the increasing mortality from extreme heat, very limited studies have quantified the effects of summer extreme temperature on heat-related illnesses in China. METHODS: The associations between extreme heat and daily heat-related illnesses that occurred in the summers of 2011-2013 in Ningbo, China, have been examined, using a distributed lag non-linear model (DLNM) based on 3862 cases. The excess morbidities of heat-related illness during each heat wave have been calculated separately and the cumulative heat wave effects on age-, sex-, and cause-specific illnesses in each year along lags have been estimated as well. RESULTS: After controlling the effect of relative humidity, it is found that maximum temperature, rather than heat index, was a better predictor of heat-related illnesses in summers. A positive association between maximum temperatures and occurrence of heat-related diseases was apparent, especially at short lag effects. Six heat waves during the period of 2011-2013 were identified and all associated with excess heat-related illnesses. Relative to the average values for the corresponding periods in 2011 and 2012, a total estimated 679 extra heat-related illnesses occurred during three heat waves in 2013. The significant prolonged heat wave effects on total heat-related illnesses during heat waves in three study years have also been identified. The strongest cumulative effect of heat waves was on severe heat diseases in 2013, with a 10-fold increased risk. More males than females, individuals with more severe forms of illness, were more affected by the heat. However, all age groups were vulnerable. CONCLUSIONS: Recent heat waves had a substantial and delayed effect on heat illnesses in Ningbo. Relevant active well-organized public health initiatives should be implemented to reduce the adverse effects of heat extremes on the illnesses.