Xin Fang

Concentration-Response Relationship between PM2.5 and Daily Respiratory Deaths in China: A Systematic Review and Metaregression Analysis of Time-Series Studies

The association between the particulate matters with aerodynamic diameter ≤ 2.5 μm (PM2.5) and daily respiratory deaths, particularly the concentration-response pattern, has not been fully examined and established in China. We conducted a systematic review of time-series studies to compile information on the associations between PM2.5 concentration and respiratory deaths and used metaregression to assess the concentration-response relationship. Out of 1,957 studies screened, eleven articles in English and two articles in Chinese met the eligibility criteria. For single-day lags, per 10 μg/m3 increase in PM2.5 concentration was associated with 0.30 [95% confidence interval (CI): 0.10, 0.50] percent increase in daily respiratory deaths; for multiday lags, the corresponding increase in respiratory deaths was 0.69 (95% CI: 0.55, 0.83) percent. Difference in the effects was observed between the northern cities and the south cities in China. No statistically significant concentration-response relationship between PM2.5 concentrations and their effects was found. With increasingly wider location coverage for PM2.5 data, it is crucial to further investigate the concentration-response pattern of PM2.5 effects on respiratory and other cause-specific mortality for the refinement and adaptation of global and national air quality guidelines and targets.

Dose-Response Relationship between Dietary Magnesium Intake and Risk of Type 2 Diabetes Mellitus: A Systematic Review and Meta-Regression Analysis of Prospective Cohort Studies

The epidemiological evidence for a dose-response relationship between magnesium intake and risk of type 2 diabetes mellitus (T2D) is sparse. The aim of the study was to summarize the evidence for the association of dietary magnesium intake with risk of T2D and evaluate the dose-response relationship. We conducted a systematic review and meta-analysis of prospective cohort studies that reported dietary magnesium intake and risk of incident T2D. We identified relevant studies by searching major scientific literature databases and grey literature resources from their inception to February 2016. We included cohort studies that provided risk ratios, i.e., relative risks (RRs), odds ratios (ORs) or hazard ratios (HRs), for T2D. Linear dose-response relationships were assessed using random-effects meta-regression. Potential nonlinear associations were evaluated using restricted cubic splines. A total of 25 studies met the eligibility criteria. These studies comprised 637,922 individuals including 26,828 with a T2D diagnosis. Compared with the lowest magnesium consumption group in the population, the risk of T2D was reduced by 17% across all the studies; 19% in women and 16% in men. A statistically significant linear dose-response relationship was found between incremental magnesium intake and T2D risk. After adjusting for age and body mass index, the risk of T2D incidence was reduced by 8%–13% for per 100 mg/day increment in dietary magnesium intake. There was no evidence to support a nonlinear dose-response relationship between dietary magnesium intake and T2D risk. The combined data supports a role for magnesium in reducing risk of T2D, with a statistically significant linear dose-response pattern within the reference dose range of dietary intake among Asian and US populations. The evidence from Europe and black people is limited and more prospective studies are needed for the two subgroups.

Dose-response relationship between dietary magnesium intake and cardiovascular mortality: A systematic review and dose-based meta-regression analysis of prospective studies

BACKGROUND Although epidemiology studies have reported the relationship, including a dose-response relationship, between dietary magnesium intake and risk of cardiovascular disease (CVD), the risk for CVD mortality is inconclusive and the evidence for a dose-response relationship has not been summarized. OBJECTIVE We conducted a systematic review and meta-analysis of prospective studies to summarize the evidence regarding the association of dietary magnesium intake with risk of CVD mortality and describe their dose-response relationship. DESIGN We identified relevant studies by searching major scientific literature databases and grey literature resources from their inception to August 2015, and reviewed references lists of retrieved articles. We included population-based studies that reported mortality risks, i.e. relative risks (RRs), odds ratios (ORs) or hazard ratios (HRs) of CVD mortality or cause-specific CVD death. Linear dose-response relationships were assessed using random-effects meta-regression. Potential nonlinear associations were evaluated using restricted cubic splines. RESULTS Out of 3002 articles, 9 articles from 8 independent studies met the eligibility criteria. These studies comprised 449,748 individuals and 10,313 CVD deaths. Compared with the lowest dietary magnesium consumption group in the population, the risk of CVD mortality was reduced by 16% in women and 8% in men. No significant linear dose-response relationship was found between increment in dietary magnesium intake and CVD mortality across all the studies. After adjusting for age and BMI, the risk of CVD mortality was reduced by 24-25% per 100mg/d increment in dietary magnesium intake in women of all the participants and in all the US participants. CONCLUSION Although the combined data confirm the role of dietary magnesium intake in reducing CVD mortality, the dose-response relationship was only found among women and in US population.

Bayesian model averaging method for evaluating associations between air pollution and respiratory mortality: a time-series study

Objective To demonstrate an application of Bayesian model averaging (BMA) with generalised additive mixed models (GAMM) and provide a novel modelling technique to assess the association between inhalable coarse particles (PM10) and respiratory mortality in time-series studies. Design A time-series study using regional death registry between 2009 and 2010. Setting 8 districts in a large metropolitan area in Northern China. Participants 9559 permanent residents of the 8 districts who died of respiratory diseases between 2009 and 2010. Main outcome measures Per cent increase in daily respiratory mortality rate (MR) per interquartile range (IQR) increase of PM10 concentration and corresponding 95% confidence interval (CI) in single-pollutant and multipollutant (including NOx, CO) models. Results The Bayesian model averaged GAMM (GAMM+BMA) and the optimal GAMM of PM10, multipollutants and principal components (PCs) of multipollutants showed comparable results for the effect of PM10 on daily respiratory MR, that is, one IQR increase in PM10 concentration corresponded to 1.38% vs 1.39%, 1.81% vs 1.83% and 0.87% vs 0.88% increase, respectively, in daily respiratory MR. However, GAMM+BMA gave slightly but noticeable wider CIs for the single-pollutant model (−1.09 to 4.28 vs −1.08 to 3.93) and the PCs-based model (−2.23 to 4.07 vs −2.03 vs 3.88). The CIs of the multiple-pollutant model from two methods are similar, that is, −1.12 to 4.85 versus −1.11 versus 4.83. Conclusions The BMA method may represent a useful tool for modelling uncertainty in time-series studies when evaluating the effect of air pollution on fatal health outcomes.

Acute Effects of Nitrogen Dioxide on Cardiovascular Mortality in Beijing : An Exploration of Spatial Heterogeneity and the District-specific Predictors

The exploration of spatial variation and predictors of the effects of nitrogen dioxide (NO2) on fatal health outcomes is still sparse. In a multilevel case-crossover study in Beijing, China, we used mixed Cox proportional hazard model to examine the citywide effects and conditional logistic regression to evaluate the district-specific effects of NO2 on cardiovascular mortality. District-specific predictors that could be related to the spatial pattern of NO2 effects were examined by robust regression models. We found that a 10 μg/m3 increase in daily mean NO2 concentration was associated with a 1.89% [95% confidence interval (CI): 1.33–2.45%], 2.07% (95% CI: 1.23–2.91%) and 1.95% (95% CI: 1.16–2.72%) increase in daily total cardiovascular (lag03), cerebrovascular (lag03) and ischemic heart disease (lag02) mortality, respectively. For spatial variation of NO2 effects across 16 districts, significant effects were only observed in 5, 4 and 2 districts for the above three outcomes, respectively. Generally, NO2 was likely having greater adverse effects on districts with larger population, higher consumption of coal and more civilian vehicles. Our results suggested independent and spatially varied effects of NO2 on total and subcategory cardiovascular mortalities. The identification of districts with higher risk can provide important insights for reducing NO2 related health hazards.

A Two-Stage Method to Estimate the Contribution of Road Traffic to PM2.5 Concentrations in Beijing, China

Background: Fine particulate matters with aerodynamic diameters smaller than 2.5 micrometers (PM2.5) have been a critical environmental problem in China due to the rapid road vehicle growth in recent years. To date, most methods available to estimate traffic contributions to ambient PM2.5 concentration are often hampered by the need for collecting data on traffic volume, vehicle type and emission profile. Objective: To develop a simplified and indirect method to estimate the contribution of traffic to PM2.5 concentration in Beijing, China. Methods: Hourly PM2.5 concentration data, daily meteorological data and geographic information were collected at 35 air quality monitoring (AQM) stations in Beijing between 2013 and 2014. Based on the PM2.5 concentrations of different AQM station types, a two-stage method comprising a dispersion model and generalized additive mixed model (GAMM) was developed to estimate separately the traffic and non-traffic contributions to daily PM2.5 concentration. The geographical trend of PM2.5 concentrations was investigated using generalized linear mixed model. The temporal trend of PM2.5 and non-linear relationship between PM2.5 and meteorological conditions were assessed using GAMM. Results: The medians of daily PM2.5 concentrations during 2013–2014 at 35 AQM stations in Beijing ranged from 40 to 92 μg/m3. There was a significant increasing trend of PM2.5 concentration from north to south. The contributions of road traffic to daily PM2.5 concentrations ranged from 17.2% to 37.3% with an average 30%. The greatest contribution was found at AQM stations near busy roads. On average, the contribution of road traffic at urban stations was 14% higher than that at rural stations. Conclusions: Traffic emissions account for a substantial share of daily total PM2.5 concentrations in Beijing. Our two-stage method is a useful and convenient tool in ecological and epidemiological studies to estimate the traffic contribution to PM2.5 concentrations when there is limited information on vehicle number and types and emission profile.

Relationship between fine particulate matter, weather condition and daily non-accidental mortality in Shanghai, China : A Bayesian approach

There are concerns that the reported association of ambient fine particulate matter (PM2.5) with mortality might be a mixture of PM2.5 and weather conditions. We evaluated the effects of extreme weather conditions and weather types on mortality as well as their interactions with PM2.5 concentrations in a time series study. Daily non-accidental deaths, individual demographic information, daily average PM2.5 concentrations and meteorological data between 2012 and 2014 were obtained from Shanghai, China. Days with extreme weather conditions were identified. Six synoptic weather types (SWTs) were generated. The generalized additive model was set up to link the mortality with PM2.5 and weather conditions. Parameter estimation was based on Bayesian methods using both the Jeffreys’ prior and an informative normal prior in a sensitivity analysis. We estimate the percent increase in non-accidental mortality per 10 μg/m3 increase in PM2.5 concentration and constructed corresponding 95% credible interval (CrI). In total, 336,379 non-accidental deaths occurred during the study period. Average daily deaths were 307. The results indicated that per 10 μg/m3 increase in daily average PM2.5 concentration alone corresponded to 0.26–0.35% increase in daily non-accidental mortality in Shanghai. Statistically significant positive associations between PM2.5 and mortality were found for favorable SWTs when considering the interaction between PM2.5 and SWTs. The greatest effect was found in hot dry SWT (percent increase = 1.28, 95% CrI: 0.72, 1.83), followed by warm humid SWT (percent increase = 0.64, 95% CrI: 0.15, 1.13). The effect of PM2.5 on non-accidental mortality differed under specific extreme weather conditions and SWTs. Environmental policies and actions should take into account the interrelationship between the two hazardous exposures.

Exogenous PTHrP Repairs the Damaged Fracture Healing of PTHrP+/- Mice and Accelerates Fracture Healing of Wild Mice

Bone fracture healing is a complicated physiological regenerative process initiated in response to injury and is similar to bone development. To demonstrate whether an exogenous supply of parathyroid hormone–related protein (PTHrP) helps in bone fracture healing, closed mid-diaphyseal femur fractures were created and stabilized with intramedullary pins in eight-week-old wild-type (WT) PTHrP+/+ and PTHrP+/− mice. After administering PTHrP for two weeks, callus tissue properties were analyzed at one, two, and four weeks post-fracture (PF) by various methods. Bone formation–related genes and protein expression levels were evaluated by real-time reverse transcriptase–polymerase chain reaction and Western blots. At two weeks PF, mineral density of callus, bony callus areas, mRNA levels of alkaline phosphatase (ALP), type I collagen, Runt-related transcription factor 2 (Runx-2), and protein levels of Runx-2 and insulin-like growth factor-1 decreased in PTHrP+/− mice compared with WT mice. At four weeks PF, total collagen-positive bony callus areas, osteoblast number, ALP-positive areas, and type I collagen-positive areas all decreased in PTHrP+/− mice. At both two and four weeks PF, tartrate-resistant acid phosphatase–positive osteoclast number and surface decreased a little in PTHrP+/− mice. The study indicates that exogenous PTHrP provided by subcutaneous injection could redress impaired bone fracture healing, leading to mutation of activated PTHrP by influencing callus areas, endochondral bone formation, osteoblastic bone formation, and bone turnover.

Maternal urinary carbofuranphenol levels before delivery and birth outcomes in Sheyang Birth Cohort

Exposure to carbamates has been linked with adverse health effects on developmental period. This study aimed to monitor exposure to carbofuranphenol of pregnant women from Sheyang Birth Cohort and investigate associations between prenatal exposure to carbofuranphenol and birth outcomes. During June 2009 to January 2010, 1100 pregnant women living in Sheyang County participated in our study and donated urine sample. Urinary carbofuranphenol concentration was measured by gas chromatography-tandem mass spectrometry. Associations between urinary carbofuranphenol levels and infant birth outcomes were assessed by generalized linear models. Urinary carbofuranphenol concentrations varied from 0.01 to 395.40μg/L (0.01-303.93μg/g for creatinine adjusted), the geometric mean, median and inter quartile range are 0.81μg/L (1.28μg/g cr), 0.80μg/L (1.23μg/g cr) and 0.27-2.20μg/L (0.47-3.11μg/g cr), respectively. No statistically significant association between maternal urinary carbofuranphenol levels and birth outcomes was found in total infants and female infants. In male neonates, carbofuranphenol level was significantly associated with head circumference (b=-0.226; 95% confidence interval: -0.411, -0.041; P=0.01) and ponderal index (b=0.043, 95% CI: 0.004, 0.083; P=0.03). These findings suggested that the pregnant women were generally exposed to carbofuranphenol and prenatal exposure to carbofuranphenol might have adverse effects on fetal development.

Sex Hormones, Gonadotropins, and Sex Hormone-binding Globulin in Infants Fed Breast Milk, Cow Milk Formula, or Soy Formula

Measurement of endogenous hormones in early life is important to investigate the effects of hormonally active environmental compounds. To assess the possible hormonal effects of different feeding regimens in different sample matrices of infants, 166 infants were enrolled from two U.S hospitals between 2006 and 2009. The children were classified into exclusive soy formula, cow milk formula or breast milk regimens. Urine, saliva and blood samples were collected over the first 12 months of life. Estradiol, estrone, testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and sex hormone-binding globulin (SHBG) levels were measured in the three matrices. Lower estradiol and LH levels were found in urine and saliva samples of soy formula-fed boys compared to cow formula-fed boys. Higher LH level was found in urine samples of soy formula-fed girls compared to cow formula-fed girls. However, we found neither a neonatal testosterone rise in the boys nor a gender-specific difference in testosterone levels, which suggests that urinary testosterone levels may not accurately reflect blood levels during mini-puberty. Nevertheless, our study shows that blood, urine and saliva samples are readily collectible and suitable for multi-hormone analyses in children and allow examination of hypotheses concerning endocrine effects from dietary compounds.