Associations of urinary organophosphate esters metabolites with asthma and lung function in adolescents.

BACKGROUND: Organophosphate esters (OPEs) are ubiquitously detected in environments and their exposure may affect respiratory health. However, epidemiological evidence, particularly among adolescents, is very limited. OBJECTIVE: We aimed to investigate the associations of urinary OPEs metabolites with asthma and lung function among adolescents and to identify potential effect modifiers. METHODS: Included were 715 adolescents aged 12-19 years old participating in the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Multivariable binary logistic regression and linear regression were used to assess associations with asthma and lung function, respectively. Stratified analyses were conducted to assess the effect modifications of serum sex hormones, vitamin D levels, and body mass index (BMI). RESULTS: After multivariable adjustment, we found that bis(2-chloroethyl) phosphate (BCEP) (3rd tertile [T3] vs 1st tertile [T1], OR = 1.87, 95% CI: 1.08, 3.25; P-trend=0.029) and diphenyl phosphate (DPHP) (T3 vs T1, OR = 2.52, 95%CI: 1.25, 5.04; P-trend=0.013) were associated with elevated odds of asthma in all adolescents. Sex-stratified analyses revealed that associations of these two OPEs metabolites tended to be stronger in males. Meanwhile, BCEP and the molecular sum of OPEs metabolites (∑OPEs) were significantly associated with declined lung function, either in all adolescents or by sex. Furthermore, stratified analyses revealed that positive associations of OPEs metabolites with asthma tended to be stronger among adolescents with insufficient levels of Vitamin D (VD < 50 nmol/L), relatively high levels of total testosterone (≥356 ng/dL and ≥22.5 ng/dL for males and females, respectively), or low levels of estradiol (<19.1 pg/mL and <47.3 pg/mL for males and females, respectively). SIGNIFICANCE: Certain urinary OPEs metabolites, especially DPHP and BCEP, were associated with elevated odds of asthma and declined lung function in adolescents. Such associations might be partly modified by levels of VD and sex steroid hormones. IMPACT STATEMENT: The observed associations of urinary OPEs metabolites with increased risk of asthma and declined lung function highlight the potential hazard of OPEs exposure to respiratory health among adolescents.

Associations of urinary organophosphate esters metabolites and diet quality with nonalcoholic/metabolic dysfunction-associated fatty liver diseases in adults.

Whether exposure to organophosphate esters (OPEs) is associated with metabolic dysfunction-associated fatty liver disease (MAFLD) and nonalcoholic fatty liver disease (NAFLD) remains unclear. A healthy diet is crucial to metabolic health and dietary intake is also an important route for OPEs exposure. However, the joint associations of OPEs, diet quality, and the effect modification by diet quality remain unknown. This study comprised 2618 adults with complete data on 6 urinary OPEs metabolites, 24 h dietary recalls, and definitions of NAFLD and MAFLD from the 2011-2018 National Health and Nutrition Examination Survey cycles. Multivariable binary logistic regression was applied to assess the associations of OPEs metabolites with NAFLD, MAFLD, and components of MAFLD. We also adopted the quantile g-Computation method to examine the associations of OPEs metabolites mixture. Our results revealed that OPEs metabolites mixture and three individual metabolites [i.e., bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), bis(2-chloroethyl) phosphate, and diphenyl phosphate] were significantly and positively associated with NAFLD and MAFLD (P-trend<0.001), with BDCIPP being identified as the dominant metabolite, whereas the 4 diet quality scores were monotonically and inversely associated with both MAFLD and NAFLD (P-trend<0.001). Of note, 4 diet quality scores were by and large negatively associated with BDCIPP, but not with other OPEs metabolites. Joint association analyses revealed that individuals with higher diet quality and lower BDCIPP concentration tend to have lower odds of having MAFLD and NAFLD in comparison with people in the low diet quality and high BDCIPP group, but the associations of BDCIPP were not modified by diet quality. Our findings suggest that certain OPEs metabolites and diet quality exhibited opposing associations with both MAFLD and NAFLD. Individuals adherent to a healthier diet may have a lower level of certain OPEs metabolites, and thus could have lower odds of having NAFLD and MAFLD.

Associations of metal mixtures with metabolic-associated fatty liver disease and non-alcoholic fatty liver disease: NHANES 2003-2018.

Objective: The hepatotoxicity of exposure to a single heavy metal has been examined in previous studies. However, there is limited evidence on the association between heavy metals mixture and non-alcoholic fatty liver disease (NAFLD) and metabolic-associated fatty liver disease (MAFLD). This study aims to investigate the associations of 13 urinary metals, individually and jointly, with NAFLD, MAFLD, and MAFLD components. Methods: This study included 5,548 adults from the National Health and Nutrition Examination Survey (NHANES) 2003-2018. Binary logistic regression was used to explore the associations between individual metal exposures and MAFLD, NAFLD, and MAFLD components. Bayesian kernel machine regression (BKMR) and Quantile-based g-computation (QGC) were used to investigate the association of metal mixture exposure with these outcomes. Results: In single metal analysis, increased levels of arsenic [OR 1.09 (95%CI 1.03-1.16)], dimethylarsinic acid [1.17 (95%CI 1.07-1.27)], barium [1.22 (95%CI 1.14-1.30)], cobalt [1.22 (95%CI 1.11-1.34)], cesium [1.35 (95%CI 1.18-1.54)], molybdenum [1.45 (95%CI 1.30-1.62)], antimony [1.18 (95%CI 1.08-1.29)], thallium [1.49 (95%CI 1.33-1.67)], and tungsten [1.23 (95%CI 1.15-1.32)] were significantly associated with MAFLD risk after adjusting for potential covariates. The results for NAFLD were similar to those for MAFLD, except for arsenic, which was insignificantly associated with NAFLD. In mixture analysis, the overall metal mixture was positively associated with MAFLD, NAFLD, and MAFLD components, including obesity/overweight, diabetes, and metabolic dysfunction. In both BKMR and QGC models, thallium, molybdenum, tungsten, and barium mainly contributed to the positive association with MAFLD. Conclusion: Our study indicated that exposure to heavy metals, individually or cumulatively, was positively associated with NAFLD, MAFLD, and MAFLD components, including obesity/overweight, diabetes, and metabolic dysfunction. Additional research is needed to validate these findings in longitudinal settings.

The Causal Relationship between the Morning Chronotype and the Gut Microbiota: A Bidirectional Two-Sample Mendelian Randomization Study.

BACKGROUND: Numerous observational studies have documented an association between the circadian rhythm and the composition of the gut microbiota. However, the bidirectional causal effect of the morning chronotype on the gut microbiota is unknown. METHODS: A two-sample Mendelian randomization study was performed, using the summary statistics of the morning chronotype from the European Consortium and those of the gut microbiota from the largest available genome-wide association study meta-analysis, conducted by the MiBioGen consortium. The inverse variance-weighted (IVW), weighted mode, weighted median, MR-Egger regression, and simple mode methods were used to examine the causal association between the morning chronotype and the gut microbiota. A reverse Mendelian randomization analysis was conducted on the gut microbiota, which was identified as causally linked to the morning chronotype in the initial Mendelian randomization analysis. Cochran's Q statistics were employed to assess the heterogeneity of the instrumental variables. RESULTS: Inverse variance-weighted estimates suggested that the morning chronotype had a protective effect on Family Bacteroidaceae (ß = -0.072; 95% CI: -0.143, -0.001; p = 0.047), Genus Parabacteroides (ß = -0.112; 95% CI: -0.184, -0.039; p = 0.002), and Genus Bacteroides (ß = -0.072; 95% CI: -0.143, -0.001; p = 0.047). In addition, the gut microbiota (Family Bacteroidaceae (OR = 0.925; 95% CI: 0.857, 0.999; p = 0.047), Genus Parabacteroides (OR = 0.915; 95% CI: 0.858, 0.975; p = 0.007), and Genus Bacteroides (OR = 0.925; 95% CI: 0.857, 0.999; p = 0.047)) demonstrated positive effects on the morning chronotype. No significant heterogeneity in the instrumental variables, or in horizontal pleiotropy, was found. CONCLUSION: This two-sample Mendelian randomization study found that Family Bacteroidaceae, Genus Parabacteroides, and Genus Bacteroides were causally associated with the morning chronotype. Further randomized controlled trials are needed to clarify the effects of the gut microbiota on the morning chronotype, as well as their specific protective mechanisms.

Concerns about and stimuli of COVID-19 vaccination hesitancy among diverse occupational groups in metropolitan areas of China: a cross-sectional study.

OBJECTIVES: In this study, we aimed to identify concerns and stimuli regarding COVID-19 vaccination acceptance and to compare the findings by occupation. METHODS: We conducted a cross-sectional study of individuals vaccinated against COVID-19 between 1 April and 30 June 2021 in four metropolitan areas of China. A total of 20 863 participants completed questionnaires, 20 767 of which were eligible for analysis. We used ordered logistic regression to assess the association of vaccination concerns and stimuli with vaccination hesitancy according to occupation. RESULTS: Farmers were mainly concerned about the quality of vaccines (adjusted OR (aOR): 3.18, 95% CI (CI): 1.83 to 5.54). Among civil servants, media publicity reduced hesitancy (aOR: 0.44, 95% CI: 0.21 to 0.92). Among medical staff, concerns about a short duration of protective effects increased hesitancy (aOR: 8.31, 95% CI: 2.03 to 33.99). For most occupations, concerns about side effects, poor protective effects and health status increased hesitancy. In contrast, protecting oneself and protecting others acted as a stimulus to decrease hesitancy. Interestingly, 'people around me have been vaccinated' was associated with higher vaccination hesitancy among farmers (aOR: 2.19, 95% CI: 1.20 to 4.00). CONCLUSION: The association of vaccination concerns and stimuli with vaccination hesitancy varied by occupation. The characteristics and concerns of specific target audiences should be considered when designing informational campaigns to promote vaccination against COVID-19.

Accelerate the process of getting vaccinated: factors associated with consideration of and accessibility to COVID-19 vaccination in metropolises of China.

BACKGROUND: Rapid mutation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is sweeping the world and delaying the full reopening of society. Acceleration of the vaccination process may be the key element in winning the race against this virus. We examine factors associated with personal considerations of and accessibility to the corona virus disease 2019 (COVID-19) vaccination in metropolises of China. METHODS: This multi-center, cross-sectional research was conducted using online questionnaires from April 1 to June 1, 2021, in community health service centers of Shanghai, Chengdu and Fuzhou. 9,047 vaccinated participants were included and data for 8,990 individuals were eligible for analysis. Chi-square test was conducted to find potential predictors, which were included in the logistic regressions. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the influence of region, socio-economic status (SES), and attitudes on vaccination process. RESULTS: In consideration phase, participants in Fuzhou (OR:2.26, 95%CI: 1.90 to 2.68) and Chengdu (OR: 2.48, 95%CI: 2.17 to 2.83) were more likely than those in Shanghai to consider longer than one month. These odds increased for participants with master or above degree (reference: illiteracy and primary school), higher monthly household income (reference: < ¥5000), and greater vaccination hesitancy (reference: low hesitancy). Unemployed and household-based participants (OR: 3.37, 95%CI: 1.69 to 6.75, reference: farmer) and participants without brand preference (OR:1.13, 95%CI:1.02 to 1.26) may take longer time of consideration. In the accessibility phase, participants in Fuzhou (OR: 8.82, 95%CI: 7.28 to 10.68) and Chengdu (OR: 2.28, 95%CI: 1.98 to 2.63) were more likely to wait longer than one week. These odds decreased for participants with master or above degree (reference: illiteracy and primary school), monthly household income from ¥5000 to ¥10,000 (reference: < ¥5000), and teacher or student (reference: farmer). Participants without brand preference (OR: 0.86, 95%CI: 0.77 to 0.95) were likely to wait shorter after appointment, while participants with higher risk awareness of domestic epidemic (medium, OR: 1.24, 95%CI: 1.12 to 1.37, reference: low) may wait longer. CONCLUSIONS: The influential factors changed over two phases of vaccination process. Regional disparity affected both consideration and accessibility phases. Expect that, SES, and hesitancy were major factors of the consideration phase, but had limited impact on accessibility phase.

Thirdhand smoke beliefs and behaviors among families of primary school children in Shanghai.

INTRODUCTION: There are few reports on the beliefs about thirdhand smoke in Chinese families with primary school children. This study aims to understand the beliefs about thirdhand smoke among parents or grandparents of primary school children in Shanghai and to provide an evidence base to incorporate thirdhand smoke preventative action into tobacco control interventions. METHODS: We performed a cross-sectional survey among parents and grandparents of children aged 6-13 years in the Changjiang Road Primary School and recruited 843 participants to make assessments on the 'beliefs about thirdhand smoke' (BATHS) scale. Sociodemographic details including age, gender, marital status, education level, personal income and type of home ownership (new house, secondhand house with or without redecoration) and health status of children (whether they suffered from respiratory diseases or not) were investigated. Scale assessment, univariate and multivariate analyses to explore the factors influencing the BATHS scale and subscale scores, were performed using SPSS version 22.0. RESULTS: Participants who were aged >65 years were more likely to get lower scores on the BATHS scale (OR=0.476; 95% CI: 0.311-0.728, p=0.001). Undergraduates (OR=1.190; 95% CI: 1.020-1.388, p=0.027) and graduates (OR=1.4490; 95% CI: 1.102-1.906, p=0.008) obtained higher scores. Moreover, the scores of residents living in a secondhand house with redecoration (OR=0.882; 95% CI: 0.782-0.995, p=0.041) and without redecoration (OR=0.801; 95% CI: 0.698-0.919, p=0.002) were lower compared with those of new-house owners. The scores for participants whose children suffered from respiratory diseases in the past six months (OR=1.104; 95% CI: 1.003-1.216, p=0.043) were higher than those whose children had no respiratory diseases. CONCLUSIONS: This study shows that younger people, females, those with higher incomes, and higher education levels, were more likely to believe the thirdhand smoke impacts on health and its persistence in the environment. Our findings can guide targeted actions for smoke-free home interventions.

Assessment of the association between ACYP2 and laryngeal squamous cell carcinoma risk in Chinese males.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is one of the most prevalent malignant neoplasms of the upper respiratory tract. Studies have confirmed that an unstable chromosome constitution promotes the progress of laryngeal tumorigenesis, and ACYP2 has been confirmed as a telomere length-related gene. However, to date, the association between ACYP2 polymorphisms and LSCC susceptibility has not been investigated. METHODS: We performed this study to explore the effect of 11 single-nucleotide polymorphisms (SNPs) in ACYP2 on LSCC susceptibility in Chinese Han males. Unconditional logistic regression analysis adjusted for age was used to calculate the odds ratios and 95% confidence intervals. RESULTS: Based on allele and genotype models, our results showed that rs1682111 variant was significantly associated with a decreased LSCC susceptibility (p < 0.05). On the contrary, polymorphisms of rs10439478, rs11125529, rs12615793, rs843711, rs11896604, and rs17045754 were significantly associated with an increased LSCC risk (p < 0.05). The results of haplotype analysis indicated that haplotypes "TTCTCG" and "TTCTAA" in block 1 and "TG" in block 2 showed a risk factor for the development of LCSS (p = 0.009, p < 0.001, and p = 0.001, respectively). The results of Genotype-Tissue Expression analysis indicate that these significant SNPs were known to be associated with ACYP2 expression. CONCLUSION: Our data demonstrated that ACYP2 polymorphisms may exert effects on LSCC susceptibility in Chinese Han males.

Single-nucleotide polymorphisms of MMP2 in MMP/TIMP pathways associated with the risk of alcohol-induced osteonecrosis of the femoral head in Chinese males: A case-control study.

The proportion of alcohol-induced osteonecrosis of the femoral head (ONFH) in all ONFH patients was 30.7%, with males prevailing among the ONFH patients in mainland China (70.1%). Matrix metalloproteinase 2 (MMP2), a member of the MMP gene family, encodes the enzyme MMP2, which can promote osteoclast migration, attachment, and bone matrix degradation. In this case-control study, we aimed to investigate the association between MMP2 and the alcohol-induced ONFH in Chinese males.In total, 299 patients with alcohol-induced ONFH and 396 healthy controls were recruited for a case-control association study. Five single-nucleotide polymorphisms within the MMP2 locus were genotyped and examined for their correlation with the risk of alcohol-induced ONFH and treatment response using Pearson χ test and unconditional logistic regression analysis. We identified 3 risk alleles for carriers: the allele "T" of rs243849 increased the risk of alcohol-induced ONFH in the allele model, the log-additive model without adjustment, and the log-additive model with adjustment for age. Conversely, the genotypes "CC" in rs7201 and "CC" in rs243832 decreased the risk of alcohol-induced ONFH, as revealed by the recessive model. After the Bonferroni multiple adjustment, no significant association was found. Furthermore, the haplotype analysis showed that the "TT" haplotype of MMP2 was more frequent among patients with alcohol-induced ONFH by unconditional logistic regression analysis adjusted for age.In conclusion, there may be an association between MMP2 and the risk of alcohol-induced ONFH in North-Chinese males. However, studies on larger populations are needed to confirm this hypothesis; these data may provide a theoretical foundation for future studies.

Effect of epidermal growth factor receptor gene polymorphisms on prognosis in glioma patients.

Previous studies suggested that single nucleotide polymorphisms (SNPs) in epidermal growth factor receptor (EGFR) are associated with risk of glioma. However, the associations between these SNPs and glioma patient prognosis have not yet been fully investigated. Therefore, the present study was aimed to evaluate the effects of EGFR polymorphisms on the glioma patient prognosis. We retrospectively evaluated 269 glioma patients and investigated associations between EGFR SNPs and patient prognosis using Cox proportional hazard models and Kaplan-Meier curves. Univariate analysis revealed that age, gross-total resection and chemotherapy were associated with the prognosis of glioma patients (p < 0.05). In addition, four EGFR SNPs (rs11506105, rs3752651, rs1468727 and rs845552) correlated with overall survival (OS) (Log-rank p = 0.011, 0.020, 0.008, and 0.009, respectively) and progression-free survival PFS (Log-rank p = 0.026, 0.024, 0.019 and 0.009, respectively). Multivariate analysis indicated that the rs11506105 G/G genotype, the rs3752651 and rs1468727 C/C genotype and the rs845552 A/A genotype correlated inversely with OS and PFS. In addition, OS among patients with the rs730437 C/C genotype (p = 0.030) was significantly lower OS than among patients with A/A genotype. These data suggest that five EGFR SNPs (rs11506105, rs3752651, rs1468727, rs845552 and rs730437) correlated with glioma patient prognosis, and should be furthered validated in studies of ethnically diverse patients.

Study of the inflammatory response of immunocytes to polymerized porcine hemoglobin (pPolyHb).

Polymerized porcine hemoglobin (pPolyHb), which was synthesized from chemically modified porcine hemoglobin, can carry and deliver oxygen to tissues in addition to restoring intravascular volume. Assessment of the inflammatory response generated in the host is a part of the overall safety evaluation of pPolyHb. In this study, we measured the levels of IL-1ß, IL-10, and CD11b/CD18 in response to pPolyHb stimulation, both in vivo (in rats) and in vitro. Our results suggest that the levels of these indicators are not statistically changed by pPolyHb, indicating that pPolyHb is not immunotoxic to cells and animals in this respect.

The protective effect of polymerized porcine hemoglobin (pPolyHb) on transient focal cerebral ischemia/reperfusion injury.

Glutaraldehyde-polymerized porcine hemoglobin (pPolyHb) is a hemoglobin-based oxygen carrier currently being developed as a potential red blood cell substitute. We assessed the protective effect of pPolyHb on transient focal cerebral ischemia/reperfusion (I/R) injury. Several outcomes were tested, including infarct size, neurological score, production of inflammatory factors, and markers of oxidative status. Our results show that pPolyHb can not only significantly reduce infarct volume and improve neurological score, but can also inhibit the expression of TNF-α and IL-1ß. Furthermore, the generation of MDA and MPO was reduced by pPolyHb. We conclude that pPolyHb has a positive effect on transient focal cerebral I/R injury.

Pretreatment with pPolyHb attenuates H2O2-induced endothelial cell injury through inhibition of JNK/p38 MAPK pathway by upregulation of heme oxygenase-1.

Polymerized porcine hemoglobin (pPolyHb) exhibits a protective effect on ischemia/reperfusion of organ grafts. A series of experiments were performed to explore the underlying cytoprotective mechanisms of pPolyHb pretreatment on H2O2-induced cell death and apoptosis. The results showed that the pretreatment augmented heme oxygenase-1 (HO-1) expression, and at the same time, decreased the phosphorylation of JNK/p38 mitogen-activated protein kinase (MAPK) and intracellular ROS generation in H2O2-treated HUVECs. Moreover, the inhibition of HO-1 expression by tin porphyrin (SnPP) abolished the protective effects of pPolyHb, which suggested that the cytoprotective effect of pPolyHb involves upregulating HO-1 and subsequently decreasing the phosphorylation of the JNK and p38 MAPK and ROS generation.