Long-term PM2.5 exposure in association with chronic respiratory diseases morbidity: A cohort study in Northern China.

Several literatures have examined the risk of chronic respiratory diseases in association with short-term ambient PM2.5 exposure in China. However, little evidence has examined the chronic impacts of PM2.5 exposure on morbidity of chronic respiratory diseases in cohorts from high pollution countries. Our study aims to investigate the associations. Based on a retrospective cohort among adults in northern China, a Cox regression model with time-varying PM2.5 exposure and a concentration-response (C-R) curve model were performed to access the relationships between incidence of chronic respiratory diseases and long-term PM2.5 exposure during a mean follow-up time of 9.8 years. Individual annual average PM2.5 estimates were obtained from a satellite-based model with high resolution. The incident date of a chronic respiratory disease was identified according to self-reported physician diagnosis time and/or intake of medication for treatment. Among 38,047 urban subjects analyzed in all-cause chronic respiratory disease cohort, 482 developed new cases. In CB (38,369), asthma (38,783), and COPD (38,921) cohorts, the onsets were 276, 89, and 14, respectively. After multivariable adjustment, hazard ratio and 95% confidence interval for morbidity of all-cause chronic respiratory disease, CB, asthma, and COPD were 1.15 (1.01, 1.31), 1.20 (1.00, 1.42), 0.76 (0.55, 1.04), and 0.66 (0.29, 1.47) with each 10 µg/m3 increment in PM2.5, respectively. Stronger effect estimates were suggested in alcohol drinkers across stratified analyses. Additionally, the shape of C-R curve showed an increasing linear relationship before 75.00 µg/m3 concentrations of PM2.5 for new-onset all-cause chronic respiratory disease, and leveled off at higher levels. These findings indicated that long-term exposure to high-level PM2.5 increased the risks of incident chronic respiratory diseases in China. Further evidence of C-R curves is warranted to clarify the associations of adverse chronic respiratory outcomes involving air pollution.

Long-term exposure to ambient PM2.5 and stroke mortality among urban residents in northern China.

Evidence is still limited for the role of long-term PM2.5 exposure in cerebrovascular diseases among residents in high pollution regions. The study is aimed to investigate the long-term effects of PM2.5 exposure on stroke mortality, and further explore the effect modification of temperature variation on the PM2.5-mortality association in northern China. Based on a cohort data with an average follow-up of 9.8 years among 38,435 urban adults, high-resolution estimates of PM2.5 derived from a satellite-based model were assigned to each participant. A Cox regression model with time-varying exposures and strata of geographic regions was employed to assess the risks of stroke mortality associated with PM2.5, after adjusting for individual risk factors. The cross-product term of PM2.5 exposure and annual temperature range was further added into the regression model to test whether the long-term temperature variation would modify the association of PM2.5 with stroke mortality. Among the study participants, the annual mean level of PM2.5 concentration was 66.3 µg/m3 ranging from 39.0 µg/m3 to 100.6 µg/m3. For each 10 µg/m3 increment in PM2.5, the hazard ratio (HR) was 1.31 (95% CI: 1.04-1.65) for stroke mortality after multivariable adjustment. In addition, the HRs of PM2.5 decreased gradually as the increase of annual temperature range with the HRs of 1.95 (95% CI: 1.36-2.81), 1.53 (95% CI: 1.06-2.22), and 1.11 (95% CI: 0.75-1.63) in the low, middle, and high group of annual temperature range, respectively. The findings provided further evidence of long-term PM2.5 exposure on stroke mortality in high-exposure settings such as northern China, and also highlighted the view that assessing the adverse health effects of air pollution might not ignore the role of temperature variations in the context of climate change.

Associations between the incidence and mortality rates of type 2 diabetes mellitus and long-term exposure to ambient air pollution: A 12-year cohort study in northern China.

BACKGROUND: Ambient air pollution has recently been related to type 2 diabetes mellitus (T2DM), a disease that has caused an economic and health burden worldwide. Evidence of an association between air pollution and T2DM was reported in the United States and Europe. However, few studies have focused on the association with high levels of air pollutants in a developing country. OBJECTIVES: We conducted a 12-year cohort study to assess the incidence and mortality of T2DM associated with long-term exposure to PM10, SO2, and NO2. METHODS: A retrospective cohort with participants from four cities in northern China was conducted to assess mortality and incidence of T2DM from 1998 to 2009. Incidence of T2DM was self-reported, and incident intake of an antidiabetic drug or injection of insulin simultaneously and mortality of T2DM was obtained from a family member and double checked against death certificates provided from the local center for disease control and prevention. Individual pollution exposures were the mean concentrations of pollutants estimated from the local environmental monitoring centers over the survival years. Hazard ratios (HRs) were estimated using Cox regression models after adjusting for potential confounding factors. RESULTS: A total of 39 054 participants were recruited into the mortality cohort, among which 59 subjects died from T2DM; 38 529 participants were analyzed in the incidence cohort, and 1213 developed new cases of T2DM. For each 10 µg/m3 increase in PM10, SO2, and NO2, the adjusted HRs and 95% confidence interval (CI) for diabetic incidence were 1.831 (1.778, 1.886), 1.287 (1.256, 1.318), and 1.472 (1.419, 1.528), respectively. Similar results can be observed in the analysis of diabetic mortality with HRs (95% CI) up to 2.260 (1.732, 2.950), 1.130 (1.042, 1.225), and 1.525 (1.280, 1.816), respectively. CONCLUSIONS: Our results suggested that long-term exposure to high levels of PM10, SO2, and NO2 increase risk of incident and mortality of T2DM in China.

The impact of chronic environmental metal and benzene exposure on human urinary metabolome among Chinese children and the elderly population.

The health effects of metals and benzene exposure have been extensively investigated; however, information on the impact of chronic environmental metal and benzene exposure on human urinary metabolome is limited. In this study, a total of 566 participants, including 352 elderly and 214 children, were split into the "exposed" and "control" groups. The urine samples of all the participants were collected and stored at - 80 °C until analysis. The urinary levels of 17 metals and S-phenylmercapturic acid (S-PMA) were determined by the ICP-MS and LC-MS/MS methods to comprehensively assess the personal metal and benzene exposure levels, respectively. Then, the individual levels of metal and benzene exposure were correlated to the metabolic consequences of ambient pollutant exposure, which were previously observed in our metabolomics study. As a result, multiple metals, including Cd, Co, Cr, Cu, Fe, Hg, Li, Mo, Ni, Pb, Se, and Zn, exhibited a significant linear dose-dependent association with one or more urinary metabolites, including two amino acids (pyroglutamic acid and 3-methylhistidine), three organic acids (azelaic acid, decenedioic acid, and hydroxytetradecanedioic acid), ten medium-chainacylcarnitines (heptenedioylcarnitine, octenedioylcarnitine, nonenedioylcarnitine, decenedioylglucuronide, 3-hydroxydecanoylcarnitine, dodecanedioylcarnitine, nonanoylcarnitine, decadienylcarnitine, hydroxydodecenoylcarnitine, dodecadienylcarnitine, and dodecenoylcarnitine), and one glucuronide conjugate (decenedioylglucuronide). These observations indicate that the increased environmental metal exposure has caused various oxidative stress-related effects, including the depletion of antioxidants, accelerated muscle proteolysis, elevated activity of UGTs, increased lipid peroxidation, and the disorder of mitochondrial lipid metabolism among exposed children and the elderly. The current study provides new insights into the biological effects induced by metal exposure in the environment.

Identification and Characterization of Clostridium difficile Sequence Type 37 Genotype by Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry.

Clostridium difficile multilocus sequence type 37 (ST37), which mainly corresponds to ribotype 017, has been a dominant genotype circulating in China. In this study, we report the use of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) to analyze and characterize 204 C. difficile clinical isolates, including 49 ST37 and 155 non-ST37 isolates collected in China and other countries. The distributions of two major protein peaks (m/z 3,242 and 3,286) were significantly different between ST37 and non-ST37 prototype strains and clinical isolates. This difference was reproducible when analysis was performed on different colonies in different runs. This finding was repeated and confirmed by both bioMérieux Vitek MS and Bruker Microflex LT systems on isolates recovered from a variety of geographic regions worldwide. The combination of the two peaks was present in 47 of 49 ST37 isolates, resulting in a sensitivity of 95.9%. In contrast, the peak combination was absent in 153 of 155 non-ST37 isolates, resulting in a specificity of 98.7%. Our results suggest that MALDI-TOF MS is a rapid and reliable tool to identify C. difficile genotype ST37. Work is in progress to characterize the two molecules having peaks at m/z 3,242 and 3,286, which appear to be specific to C. difficile genotype ST37.

Human metabolic responses to chronic environmental polycyclic aromatic hydrocarbon exposure by a metabolomic approach.

The toxicities of polycyclic aromatic hydrocarbons (PAHs) have been extensively explored due to their carcinogenic and mutagenic potency; however, little is known about the metabolic responses to chronic environmental PAH exposure among the general population. In the present study, 566 healthy volunteers were dichotomized into exposed and control groups to investigate PAH-induced perturbations in the metabolic profiles. Nine urine PAH metabolites were measured by a sensitive LC-MS/MS method to comprehensively evaluate the PAH exposure level of each individual, and the metabolic profiles were characterized via a LC-MS-based metabolomic approach. PAH exposure was correlated to its metabolic outcomes by linear and logistic regression analyses. Metabolites related to amino acid, purine, lipid, and glucuronic acid metabolism were significantly changed in the exposed group. 1-Hydroxyphenanthrene and dodecadienylcarnitine have potential as sensitive and reliable biomarkers for PAH exposure and its metabolic outcomes, respectively, in the general population. These findings generally support the hypothesis that environmental PAH exposure causes oxidative stress-related effects in humans. The current study provides new insight into the early molecular events induced by PAH exposure in the actual environment.

HBV precore G1896A mutation promotes growth of hepatocellular carcinoma cells by activating ERK/MAPK pathway.

Chronic hepatitis B virus (HBV) infection is one of the leading causes of hepatocellular carcinoma (HCC). The HBV genome is prone to mutate and several variants are closely related to the malignant transformation of liver disease. G1896A mutation (G to A mutation at nucleotide 1896) is one of the most frequently observed mutations in the precore region of HBV, which prevents HBeAg expression and is strongly associated with HCC. However, the mechanisms by which this mutation causes HCC are unclear. Here, we explored the function and molecular mechanisms of the G1896A mutation during HBV-associated HCC. G1896A mutation remarkably enhanced the HBV replication in vitro. Moreover, it increased tumor formation and inhibited apoptosis of hepatoma cells, and decreased the sensitivity of HCC to sorafenib. Mechanistically, the G1896A mutation could activate ERK/MAPK pathway to enhanced sorafenib resistance in HCC cells and augmented cell survival and growth. Collectively, our study demonstrates for the first time that the G1896A mutation has a dual regulatory role in exacerbating HCC severity and sheds some light on the treatment of G1896A mutation-associated HCC patients.

Regulation of Antiviral Immune Response by N 6-Methyladenosine of mRNA.

Host innate and adaptive immune responses play a vital role in clearing infected viruses. Meanwhile, viruses also evolve a series of mechanisms to weaken the host immune responses and evade immune defense. Recently, N 6-methyladenosine (m6A), the most prevalent mRNA modification, has been revealed to regulate multiple steps of RNA metabolism, such as mRNA splicing, localization, stabilization, and translation, thus participating in many biological phenomena, including viral infection. In the process of virus-host interaction, the m6A modification that presents on the virus RNA impedes capture by the pattern recognition receptors, and the m6A modification appearing on the host immune-related molecules regulate interferon response, immune cell differentiation, inflammatory cytokine production, and other immune responses induced by viral infection. This review summarizes the research advances about the regulatory role of m6A modification in the innate and adaptive immune responses during viral infections.

Long-term exposure to high particulate matter pollution and incident hypertension: a 12-year cohort study in northern China.

Numerous cohort studies have reported the association of long-term exposure to particulate matter <10 µm in diameter (PM10) and hypertension in American and European countries. However, these results have been inconsistent and subject to various confounding factors. The study aimed to explore the effect of long-term exposure to high-level concentrations of PM10 on incident hypertension in a large-scale cohort from northern China. A retrospective cohort study of 39,054 participants aged between 23 and 98 years old from four cities in northern China was followed from 1998 to 2009. Excluding those with hypertension, 37,386 non-hypertensive participants (overall population) were followed for self-reported hypertension. The individuals' exposure to PM10 was the mean concentration during the follow-up period, according to the data of local environmental monitoring centers. Hazard ratios (HRs) were calculated by Cox proportional hazards models. The adjusted potential confounding factors included sociodemographic information, lifestyle, and diet. There were 2619 (7.0%) incident cases of hypertension among the overall population. In multivariable models, the HR (95% CI) of incident hypertension was 1.537 (1.515, 1.560) for each 10 µg/m3 increase in PM10. Stratified analyses showed individuals (age <65) were prone to developing hypertension. Moreover, the effects of PM10 increased and produced an HR (95% CI) of 1.555 (1.527, 1.584) for the healthy population in the sensitivity analysis. We found that the association between long-term exposure to PM10 air pollution and incident hypertension was significantly positive.

Association between long-term exposure to Sulfur dioxide pollution and hypertension incidence in northern China: a 12-year cohort study.

Several studies have researched the short-term effect of sulfur dioxide (SO2) exposure on hypertension. However, no evidence has provided the relationship between long-term high pollution exposure of SO2 and morbidity of hypertension in cohort studies in China. This retrospective cohort study aimed to evaluate this association. We used Cox proportional hazards regression models to examine the hazard ratios (HR) for hypertension risks from 1998 to 2009 associated with accumulative exposure of air SO2 among adults in northern China. Annual average concentrations of sulfur dioxide (SO2) were obtained from 15 local environmental monitoring centers. Hypertension was identified according to self-reported diagnostic time and treatment for hypertension with anti-hypertensive medication. Among 37,386 participants, 2619 new cases of hypertension were identified during 426,334 person-years. In the fully adjusted model, HR and 95% confidence interval (CI) of hypertension incidence for each 10 µg/m3 increase in SO2 were 1.176 (1.163 and 1.189). Results from stratified analyses suggested that effects of SO2 on hypertension morbidity were more pronounced in participants < 60 years old, tea drinkers, and those with high education, high poultry consumption, and active (occasional and frequent) exercise. We found that long-term exposure to high levels of SO2 increased the risk of incidence of hypertension in China.

Long-term exposure to urban air pollution and lung cancer mortality: A 12-year cohort study in Northern China.

Cohort evidence that links long-term exposures to air pollution and mortality comes largely from the United States and European countries. We investigated the relationship between long-term exposures to particulate matter <10µm in diameter (PM10), nitrogen dioxide (NO2), and sulfur dioxide (SO2) and mortality of lung cancer in Northern China. A cohort of 39,054 participants were followed during 1998-2009. Annual average concentrations for PM10, NO2, and SO2 were determined based on data collected from central monitoring stations. Lung cancer deaths (n=140) were obtained from death certificates, and hazard ratios (HRs) were estimated using Cox proportional hazards models, adjusting for age, gender, BMI, education, marital status, smoking status, passive smoking, occupation, alcohol consumption, etc. Each 10mg/m(3) increase in PM10 concentrations was associated with a 3.4%-6.0% increase in lung cancer mortality in the time-varying exposure model and a 4.0%-13.6% increase in the baseline exposure model. In multi-pollutant models, the magnitude of associations was attenuated, most strongly for PM10. The association was different in men and women, also varying across age categories and different smoking status. Substantial differences exist in the risk estimates for participants based on assignment method for air pollution exposure.

Population-based reference for birth weight for gestational age in northern China.

BACKGROUND: Localized birth weight references for gestational age serve as an essential tool in accurate evaluation of atypical birth outcomes (e.g. small for gestational age) in clinical diagnosis and region-specific epidemiological studies. Such standards are currently not available in Mainland China. AIMS: To construct up-to-date, sex- and parity-specific birth weight references based on 231,937 births in Taiyuan, China during years 2005-2011. STUDY DESIGN: Population-based, cross-sectional. SUBJECTS: Hospital-registered, healthy infants with births dated between 11/01/2005 and 12/31/2011 within Taiyuan area. OUTCOME MEASURES: Birth weight in grams, and gestational age in complete weeks were calculated using a combination of last-menstrual-date-based estimation and ultrasound examination. RESULTS: Separate birth weight references are constructed for male and female infants born from primiparous and multiparous mothers. Male infants are found to weigh more than female infants in later gestational ages (appr. weeks 33-42), and infants born to multiparous mother are found to weigh more than infants born to primiparous mothers in later gestational ages (appr. weeks 36-42). CONCLUSIONS: The Taiyuan birth weight reference curves display similar trends of growth as reference curves from other countries worldwide (Netherlands, Scotland, Australia, Canada, Hong Kong, Korea and Kuwait). However, growth of birth weight for Taiyuan infants tends to be slower compared to European and North American infants regardless of gender, but similar to infants from other Asian countries.

Long-term exposure to high particulate matter pollution and cardiovascular mortality: a 12-year cohort study in four cities in northern China.

Epidemiologic studies have demonstrated that long-term exposure to relatively low levels of particulate air pollution is associated with adverse cardiovascular outcomes in Europe and North America. However, few studies have assessed the association with high level air pollutants. We aimed to assess the cardiovascular effects of long-term exposure to high level concentrations of inhalable particulate and to identify the characteristics of the Chinese population that are susceptible to the health effects. A retrospective cohort, containing 39,054 subjects from four cities in northern China, was followed for mortality of all cause and specific cardiovascular diseases from 1998 to 2009. Information on concentrations of PM10 (particulate matter<10 µm in aerodynamic diameter) was collected from the local Environmental Monitoring Centers. The estimated exposure for the study participants was the mean concentration of PM10 over their surviving years during the cohort period. Relative risk values were obtained using Cox proportional hazards regression models after adjusting for potential confounding factors. For each 10 µg/m(3) increase in PM10, the relative risk ratios (RRs) of all-cause mortality, cardiovascular disease mortality, ischemic heart disease mortality, heart failure disease mortality, and cerebrovascular disease mortality were 1.24 (95% CI, 1.22-1.27), 1.23 (95% CI, 1.19-1.26), 1.37 (95% CI, 1.28-1.47), 1.11(95% CI, 1.05-1.17), and 1.23(95% CI:1.18-1.28), respectively. Results from stratified analyses suggest that the effects of PM10 on cardiovascular mortality were more pronounced in males, smokers and people with a higher socioeconomic status. Long-term exposure to PM10 increases mortality from cardiovascular disease, especially from ischemic heart disease and this association seemed to be modified by other factors. Further research that focuses on exploring dose-response relationship and inter-population comparisons is warranted.