Potential causal links of long-term exposure to PM2.5 and its chemical components with the risk of nasopharyngeal carcinoma recurrence: A 10-year cohort study in South China.

There is a lack of evidence from cohort studies on the causal association of long-term exposure to ambient fine particulate matter (PM2.5) and its chemical components with the risk of nasopharyngeal carcinoma (NPC) recurrence. Based on a 10-year prospective cohort of 1184 newly diagnosed NPC patients, we comprehensively evaluated the potential causal links of ambient PM2.5 and its chemical components including black carbon (BC), organic matter (OM), sulfate (SO4 2-), nitrate (NO3 -), and ammonium (NH4 +) with the recurrence risk of NPC using a marginal structural Cox model adjusted with inverse probability weighting. We observed 291 NPC patients experiencing recurrence during the 10-year follow-up and estimated a 33% increased risk of NPC recurrence (hazard ratio [HR]: 1.33, 95% confidence interval [CI]: 1.02-1.74) following each interquartile range (IQR) increase in PM2.5 exposure. Each IQR increment in BC, NH4 +, OM, NO3 -, and SO4 2- was associated with HRs of 1.36 (95%CI: 1.13-1.65), 1.35 (95%CI: 1.07-1.70), 1.33 (95%CI: 1.11-1.59), 1.32 (95%CI: 1.06-1.64), 1.31 (95%CI: 1.08-1.57). The elderly, patients with no family history of cancer, no smoking history, no drinking history, and those with severe conditions may exhibit a greater likelihood of NPC recurrence following exposure to PM2.5 and its chemical components. Additionally, the effect estimates of the five components are greater among patients who were exposed to high concentration than in the full cohort of patients. Our study provides solid evidence for a potential relationship between long-term exposure to PM2.5 and its components and the risk of NPC recurrence.

Unveiling causal connections: Long-term particulate matter exposure and type 2 diabetes mellitus mortality in Southern China.

Evidence of the potential causal links between long-term exposure to particulate matters (PM, i.e., PM1, PM2.5, and PM1-2.5) and T2DM mortality based on large cohorts is limited. In contrast, the existing evidence usually suffers from inherent bias with the traditional association assessment. A prospective cohort of 580,757 participants in the southern region of China were recruited during 2009 and 2015 and followed up through December 2020. PM exposure at each residential address was estimated by linking to the well-established high-resolution simulation dataset. Hazard ratios (HRs) were calculated using time-varying marginal structural Cox models, an established causal inference approach, after adjusting for potential confounders. During follow-up, a total of 717 subjects died from T2DM. For every 1 µg/m3 increase in PM2.5, the adjusted HRs and 95% confidence interval (CI) for T2DM mortality was 1.036 (1.019-1.053). Similarly, for every 1 µg/m3 increase in PM1 and PM1-2.5, the adjusted HRs and 95% CIs were 1.032 (1.003-1.062) and 1.085 (1.054-1.116), respectively. Additionally, we observed a generally more pronounced impact among individuals with lower levels of education or lower residential greenness which as measured by the Normalized Difference Vegetation Index (NDVI). We identified substantial interactions between NDVI and PM1 (P-interaction = 0.003), NDVI and PM2.5 (P-interaction = 0.019), as well as education levels and PM1 (P-interaction = 0.049). The study emphasizes the need to consider environmental and socio-economic factors in strategies to reduce T2DM mortality. We found that PM1, PM2.5, and PM1-2.5 heighten the peril of T2DM mortality, with education and green space exposure roles in modifying it.

Associations Between Ambient Extreme Heat Exposure and Emergency Department Visits Related to Kidney Disease.

RATIONALE & OBJECTIVE: Extreme heat exposure is associated with multiple diseases. However, our current understanding of the specific impact of extreme heat exposure on kidney disease is limited. STUDY DESIGN: Case-crossover study. SETTING & PARTICIPANTS: 1,114,322 emergency department (ED) visits with a principal diagnosis of kidney disease were identified in New York state, 2005-2013. EXPOSURE: Extreme heat exposure was defined as when the daily temperature exceeded the 90th percentile temperature of that month during the study period in the county. OUTCOME: ED visits with a principal diagnosis of kidney disease and its subtypes (ICD-9 [International Classification of Diseases, Ninth Revision] codes 580-599, 788). ANALYTICAL APPROACH: Extreme heat exposure on the ED visit days was compared with extreme heat exposure on control days using a conditional logistic regression model, controlling for humidity, air pollutants, and holidays. The excess risk of kidney disease was calculated for a week (lag days 0-6) after extreme heat exposure during the warm season (May through September). We also stratified our estimates by sociodemographic characteristics. RESULTS: Extreme heat exposure was associated with a 1.7% (lag day 0) to 3.1% (lag day 2) higher risk of ED visits related to kidney disease; this association was stronger with a greater number of extreme heat exposure days in the previous week. The association with extreme heat exposure lasted for an entire week and was stronger in the transitional months (ie, May and September; excess rates ranged from 1.8% to 5.1%) rather than the summer months (June through August; excess rates ranged from 1.5% to 2.7%). The strength of association was greater among those with ED visits related to acute kidney injury, kidney stones, and urinary tract infections. Age and sex may modify the association between extreme heat exposure and ED visits. LIMITATIONS: Individual exposure to heat-how long people were outside or whether they had access to air conditioning-was unknown. CONCLUSIONS: Extreme heat exposure was significantly associated with a dose-dependent greater risk of ED visits for kidney disease.

Potential causal links between long-term ambient particulate matter exposure and cardiovascular mortality: New evidence from a large community-based cohort in South China.

BACKGROUND: Cardiovascular disease (CVD) mortality is associated with long-term particulate matter (PM) exposure. However, evidence from large, highly-exposed population cohort and observational-data-based causal inference approaches remains limited. AIMS: We examined the potential causal links between PM exposure and the CVD mortality in South China. METHODS: 580,757 participants were recruited during 2009-2015 and followed up through 2020. Satellite-based annual concentrations of PM2.5, PM10, and PMcoarse (i.e., PM10 - PM2.5) at 1 km2 spatial resolution were estimated and assigned to each participant. Marginal structural Cox models with time-varying covariates, adjusted using inverse probability weighting, were developed to evaluate the association between prolonged PM exposure and CVD mortality. RESULTS: For overall CVD mortality, the hazard ratios and 95% confidence interval for each 1 µg/m3 increase in the annual average concentration of PM2.5, PM10, and PMcoarse were 1.033 (1.028-1.037), 1.028 (1.024-1.032), and 1.022 (1.012-1.033), respectively. All three PMs were linked to a higher mortality risk for myocardial infarction and ischemic heart disease (IHD). The mortality risk of chronic IHD and hypertension was linked to PM2.5 and PM10. Significant association between PMcoarse and other heart disease mortality was also observed. The older, women, less-educated participants, or inactive participants exhibited particularly higher susceptibility. Participants who were generally exposed to PM10 concentrations below 70 µg/m3 were more vulnerable to PM2.5-, PM10- and PMcoarse-CVD mortality risks. CONCLUSION: This large cohort study provides evidence for the potential causal links between increased CVD mortality and ambient PM exposure, as well as socio-demographics linked to the highest vulnerability.

The PERK/ATF4/CHOP signaling branch of the unfolded protein response mediates cisplatin-induced ototoxicity in hair cells.

Cisplatin is a widely used chemotherapeutic agent. However, its clinical application remains limited due to the high incidence of severe ototoxicity. It has been reported that the unfolded protein response (UPR) is involved in cisplatin-induced ototoxicity. However, the specific mechanism underlying its effect remains unclear. Therefore, the present study aimed to explore the sequential changes in the key UPR signaling branch and its potential pro-apoptotic role in cisplatin-induced ototoxicity. The hair cell-like OC-1 cells were treated with cisplatin for different periods and then the expression levels of the UPR- and apoptosis-related proteins were determined. The results showed that the apoptotic rate of cells was gradually increased with prolonged cisplatin treatment. Furthermore, the sequential changes in three UPR signaling branches were evaluated. The expression levels of activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP) were gradually increased with up to 12 h of cisplatin treatment. The aforementioned expression profile was consistent with that observed for the apoptosis-related proteins. Subsequently, the proportion of apoptotic cells was notably decreased in CHOP-silenced hair cell-like OC-1 cells following treatment with cisplatin. Moreover, we found significant hair cells loss and a higher level of CHOP in cisplatin-treated cochlear explants in a time-dependent manner. Overall, the present study demonstrated that the protein kinase RNA­like endoplasmic reticulum kinase (PERK)/ATF4/CHOP signaling branch could play an important role in cisplatin-induced cell apoptosis. Furthermore, the current study suggested that CHOP may be considered as a promising therapeutic target for cisplatin-induced ototoxicity.

Risk of maternal exposure to mixed air pollutants during pregnancy for congenital heart diseases in offspring.

OBJECTIVE: To explore the risk of maternal exposure to mixed air pollutants of particulate matter 1 (PM 1), particulate matter 2.5 (PM 2.5), particulate matter 10 (PM 10) and NO 2 for congenital heart disease (CHD) in offspring, and to estimate the ranked weights of the above pollutants. METHODS: 6038 CHD patients and 5227 healthy controls from 40 medical institutions in 21 cities in Guangdong Registry of Congenital Heart Disease (GRCHD) from 2007 to 2016 were included. Logistic regression model was used to estimate the effect of maternal exposure to a single air pollutant on the occurrence of CHD in offspring. Spearman correlation coefficient was used to analyze the correlation between various pollutants, and Quantile g-computation was used to evaluate the joint effects of mixed exposure of air pollutants on CHD and the weights of various pollutants. RESULTS: The exposure levels of PM 1, PM 2.5, PM 10 and NO 2 in the CHD group were significantly higher than those in the control group (all P<0.01). The correlation coefficients among PM 1, PM 2.5, PM 10 and NO 2 were greater than 0.80. PM 1, PM 2.5, PM 10 and NO 2 exposure were associated with a significantly increased risk of CHD in offspring. Mixed exposure of these closely correlated pollutants presented much stronger effect on CHD than exposure of any single pollutants. There was a monotonic increasing relationship between mixed exposure and CHD risk. For each quantile increase in mixed exposure, the risk of CHD increased by 47% ( OR=1.47, 95% CI: 1.34-1.61). Mixed exposure had greater effect on CHD in the early pregnancy compared with middle and late pregnancy, but the greatest effect was the exposure in the whole pregnancy. The weight of PM 10 is the highest in the mixed exposure (81.3%). CONCLUSIONS: Maternal exposure to the mixture of air pollutants during pregnancy increases the risk of CHD in offspring, and the effect is much stronger than that of single exposure of various pollutants. PM 10 has the largest weights and the strongest effect in the mixed exposure.

Maternal folic acid supplementation mediates the associations between maternal socioeconomic status and congenital heart diseases in offspring.

Low maternal socioeconomic status (SES) is considered as a risk factor of congenital heart diseases (CHDs) in offspring. However, the pathways underpinning the SES-CHDs associations are unclear. We assessed if first trimester maternal folic acid supplementation (FAS) is a mediator of the SES-CHDs associations. This case-control study included 8379 CHD cases and 6918 CHD-free controls from 40 participating centers in Guangdong, Southern China, 2004-2016. All fetuses were screened for CHDs using ultrasound and cases were confirmed by echocardiogram. We collected SES and FAS information during face-to-face interview by obstetricians using a structured questionnaire. Low SES was defined as education attainment <12 years, household individual income <3000 Chinese Yuan/person/month or unemployment. FAS referred to at least 0.4 mg of daily folic acid intake over 5 days/week continuously. We used causal mediation analysis to estimate the direct, indirect and proportion mediated by FAS on the SES-CHDs associations adjusted for confounders. Both low maternal income and education were significantly associated with increased risks of CHDs and lower prevalence of FAS. Low maternal FAS prevalence mediated 10% [95%CI:5%,13%] and 3% [95%CI:1%,5%] of the maternal low income-CHDs and the maternal low education-CHDs associations, respectively. In addition, FAS mediated the highest proportion of the associations between income and multiple critical CHDs [46.9%, 95%CI:24.7%,77%] and conotruncal defects [31.5%, 95%CI:17.1%,52.0%], respectively. Maternal FAS partially mediated the SES-CHDs associations, especially among the most critical and common CHDs. Promoting FAS in low SES women of childbearing age may be a feasible intervention to help prevent CHDs.

Power outage mediates the associations between major storms and hospital admission of chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the third-leading cause of death worldwide with continuous rise. Limited studies indicate that COPD was associated with major storms and related power outages (PO). However, significant gaps remain in understanding what PO's role is on the pathway of major storms-COPD. This study aimed to examine how PO mediates the major storms-COPD associations. METHODS: In this time-series study, we extracted all hospital admissions with COPD as the principal diagnosis in New York, 2001-2013. Using distributed lag nonlinear models, the hospitalization rate during major storms and PO was compared to non-major storms and non-PO periods to determine the risk ratios (RRs) for COPD at each of 0-6 lag days respectively after controlling for time-varying confounders and concentration of fine particulate matter (PM2.5). We then used Granger mediation analysis for time series to assess the mediation effect of PO on the major storms-COPD associations. RESULTS: The RRs of COPD hospitalization following major storms, which mainly included flooding, thunder, hurricane, snow, ice, and wind, were 1.23 to 1.49 across lag 0-6 days. The risk was strongest at lag3 and lasted significantly for 4 days. Compared with non-outage periods, the PO period was associated with 1.23 to 1.61 higher risk of COPD admissions across lag 0-6 days. The risk lasted significantly for 2 days and was strongest at lag2. Snow, hurricane and wind were the top three contributors of PO among the major storms. PO mediated as much as 49.6 to 65.0% of the major storms-COPD associations. CONCLUSIONS: Both major storms and PO were associated with increased hospital admission of COPD. PO mediated almost half of the major storms-COPD hospitalization associations. Preparation of surrogate electric system before major storms is essential to reduce major storms-COPD hospitalization.

Perinatal and early postnatal outcomes for fetuses with prenatally diagnosed d-transposition of the great arteries: a prospective cohort study assessing the effect of standardised prenatal consultation.

BACKGROUND: The aim of this study was to explore perinatal and early postnatal outcomes in fetuses with prenatally diagnosed d-transposition of the great arteries and impacts of standardised prenatal consultation. METHODS: All fetuses with prenatally diagnosed d-transposition of the great arteries prospectively enrolled at South China cardiac centre from 2011 to 2015. Standardised prenatal consultation was introduced in 2013 and comprehensive measures were implemented, such as establishing fetal CHD Outpatient Consultation Service, performing standard prenatal consultation according to specifications, and establishing a multidisciplinary team with senior specialists performing in-person consultations. Continuous follow-up investigation was conducted. Perinatal and postnatal outcomes were compared before and after consultation including live birth, elective termination of pregnancy, spontaneous fetal death, stillbirths, referral for surgery, and survival. RESULTS: In all, 146 fetuses were enrolled with 41 (28%) lost to follow-up. Among 105 remaining fetuses, 29 (28%) were live births and 76 (72%) were terminated. After consultation, live birth rate was higher (50 versus 33%) and termination rate was lower (50 versus 76%), although there was no statistical significance. Excluding three live births without postnatal d-transposition of the great arteries, 65% (17/26) underwent arterial switch operation within 30 days. A total of three in-hospital deaths occurred and during the 10-month follow-up period, one death was observed. In one case, the switch procedure was performed at 13 months and the infant survived. Out of eight infants without arterial switch operation, two died. CONCLUSIONS: Live birth rate increased after consultation; however, termination remained high. Combining termination, patients without arterial switch operation, and operative mortality, outcomes of d-transposition of the great arteries infants can be improved. Standard consultation, multidisciplinary collaboration, and improved perinatal care are important to improve outcomes.

Risk factors of different congenital heart defects in Guangdong, China.

BACKGROUND: Limited studies have evaluated the risk factors for congenital heart defects (CHDs) in China and compared them for different types of CHDs. This study examined risk factors between isolated and multiple CHDs as well as among CHDs subtypes in Guangdong, Southern China. METHODS: This population-based case-control study included 4,034 pairs of case and control infants enrolled in the Guangdong Registry of CHD study, 2004-2013. Multivariate logistic regression was used to compute adjusted odds ratios (ORs) while simultaneously controlling for confounders. RESULTS: Multiple maternal environmental exposures, including living in newly renovated rooms, residential proximity to main traffic, paternal smoking, and maternal occupation as manual worker, were significantly associated with CHDs with ORs ranging 1.30-9.43. Maternal perinatal diseases (including maternal fever, diabetes, influenza, and threatened abortion), maternal medication use (antibiotic use), advanced maternal age, low socioeconomic status, and paternal alcohol intake were also significantly associated with CHDs, with ORs ranging 1.60-3.96. Isolated CHDs and multiple defects have different profiles of risk factors, while subtype of CHD shares common risk factors. CONCLUSION: These results suggest that maternal environmental exposures/occupation and perinatal diseases/medication use were dominant risk factors associated with CHDs in Southern China. Isolated and multiple CHDs may have different etiologic factors.

Interventions for treating gas gangrene.

BACKGROUND: Gas gangrene is a rapidly progressive and severe disease that results from bacterial infection, usually as the result of an injury; it has a high incidence of amputation and a poor prognosis. It requires early diagnosis and comprehensive treatments, which may involve immediate wound debridement, antibiotic treatment, hyperbaric oxygen therapy, Chinese herbal medicine, systemic support, and other interventions. The efficacy and safety of many of the available therapies have not been confirmed. OBJECTIVES: To evaluate the efficacy and safety of potential interventions in the treatment of gas gangrene compared with alternative interventions or no interventions. SEARCH METHODS: In March 2015 we searched: The Cochrane Wounds Group Specialized Register, The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), Ovid MEDLINE, Ovid EMBASE, EBSCO CINAHL, Science Citation Index, the China Biological Medicine Database (CBM-disc), the China National Knowledge Infrastructure (CNKI), and the Chinese scientific periodical database of VIP INFORMATION (VIP) for relevant trials. We also searched reference lists of all identified trials and relevant reviews and four trials registries for eligible research. There were no restrictions with respect to language, date of publication or study setting. SELECTION CRITERIA: We selected randomized controlled trials (RCTs) and quasi-RCTs that compared one treatment for gas gangrene with another treatment, or with no treatment. DATA COLLECTION AND ANALYSIS: Independently, two review authors selected potentially eligible studies by reviewing their titles, abstracts and full-texts. The two review authors extracted data using a pre-designed extraction form and assessed the risk of bias of each included study. Any disagreement in this process was solved by the third reviewer via consensus. We could not perform a meta-analysis due to the small number of studies included in the review and the substantial clinical heterogeneity between them, so we produced a narrative review instead. MAIN RESULTS: We included two RCTs with a total of 90 participants. Both RCTs assessed the effect of interventions on the 'cure rate' of gas gangrene; 'cure rate' was defined differently in each study, and differently to the way we defined it in this review.One trial compared the addition of Chinese herbs to standard treatment (debridement and antibiotic treatment; 26 participants) against standard treatment alone (20 participants). At the end of the trial the estimated risk ratio (RR) of 3.08 (95% confidence intervals (CI) 1.00 to 9.46) favoured Chinese herbs. The other trial compared standard treatment (debridement and antibiotic treatment) plus topical hyperbaric oxygen therapy (HBOT; 21 participants) with standard treatment plus systemic HBOT (23 participants). There was no evidence of difference between the two groups; RR of 1.10 (95% CI 0.25 to 4.84). For both comparisons the GRADE assessment was very low quality evidence due to risk of bias and imprecision so further trials are needed to confirm these results.Neither trial reported on this review's primary outcomes of quality of life, and amputation and death due to gas gangrene, or on adverse events. Trials that addressed other therapies such as immediate debridement, antibiotic treatment, systemic support, and other possible treatments were not available. AUTHORS' CONCLUSIONS: Re-analysis of the cure rate based on the definition used in our review did not show beneficial effects of additional use of Chinese herbs or topical HBOT on treating gas gangrene. The absence of robust evidence meant we could not determine which interventions are safe and effective for treating gas gangrene. Further rigorous RCTs with appropriate randomisation, allocation concealment and blinding, which focus on cornerstone treatments and the most important clinical outcomes, are required to provide useful evidence in this area.

[Analysis of environmental risk factors in congenital heart defects].

OBJECTIVE: To explore the environmental risk factors of different categories of congenital heart defects (CHD) and provide evidence for further risk factors and prevention research of CHD phenotypes. METHODS: Data of Guangdong CHD Register Study from 2004 to 2012 were used. In the study, 3 038 CHD cases and 3 038 paired controls from 34 hospitals distributed in 17 cities were registered and related information were collected using uniform, and structured questionnaires. All the CHD phenotypes were coded according to the International Classification of Diseases 10th Revision (ICD-10) and classified into 6 categories according to their pathological features. Univariate analyses were adopted to filter potential risk factors for each category of CHD. Then multivariate conditional Logistic regression was used to calculate the odds ratios of the risk factors for each category of CHD. RESULTS: The risk factors for left-to-right shunt CHD included low (OR=2.63, 95%CI:2.04-3.39) or over birth weight (OR=2.21, 95%CI: 1.47-3.32), premature delivery (OR=1.95, 95%CI: 1.53-2.49), polyembryony (OR=1.99, 95%CI: 1.22-3.26), maternal low education, mother as factory worker (OR=1.62, 95%CI: 1.32-1.98), parity≥2 (OR=1.38, 95%CI: 1.13-1.69), maternal abnormal reproduction history (OR=2.29, 95%CI: 1.75-3.01), fever (OR=2.38, 95%CI: 1.26-4.48), virus infection (OR=1.80, 95%CI: 1.29-2.51), medicine usage (OR=1.73, 95%CI: 1.11-2.69), passive smoking (OR=1.69, 95%CI: 1.26-2.29), chemical agent contact (OR=8.71, 95%CI: 2.33-32.58), living in newly decorated houses (OR=2.56, 95%CI: 1.60-4.09) or room close to the main road (OR=1.40, 95%CI: 1.14-1.72) in the first 3 months of pregnancy and father as factory worker (OR=1.46, 95%CI: 1.23-1.73). The risk factors for pulmonary outflow tract obstruction CHD included low (OR=5.98, 95%CI: 2.88-12.44) or over birth weight (OR=6.56, 95%CI:1.19-36.26), maternal low education, parity≥2 (OR=2.08, 95%CI: 1.03-4.22), virus infection in the first 3 months of pregnancy (OR=4.30, 95%CI: 1.27-13.45). The risk factors for left ventricular outflow tract obstruction CHD included father as factory worker (OR=6.01, 95%CI:1.05-34.59). The risk factors for transposition of the great arteries included low birth weight (OR=12.93, 95%CI:1.14-146.26), maternal low education, mother as factory worker (OR=3.69, 95%CI:1.53-8.91). The risk factors for conditions with intra cardiac mixing of oxygenated and deoxygenated blood included parity=2 (OR=3.45, 95%CI: 1.42-8.38). The risk factors for other CHD included over birth weight (OR=4.87, 95%CI: 1.19-19.94), maternal abnormal reproduction history (OR=2.96, 95%CI: 1.14-7.68), virus infection (OR=4.92, 95%CI: 1.56-15.47), medicine usage (OR=4.90, 95%CI: 1.22-19.77) or passive smoking (OR=10.31, 95%CI: 1.25-85.05) in the first 3 months of pregnancy. CONCLUSION: The environmental risk factors were discrepant among different categories of CHD. Further risk factors study of CHD phenotypes should be performed specially. To prevent CHD, attention should be paid to the risk factors which are related to multi or complex categories of CHD.

The prevalence of hemophilia in mainland China: a systematic review and meta-analysis.

The prevalence of hemophilia in mainland China was unclear; therefore, we can conducted a meta-analysis using existing data to evaluate the prevalence of hemophilia and its subtypes hemophilia A (HA), hemophilia B (HB), hemophilia C (HC) and Von Willebrand disease (VWD) in mainland China. We conducted a systematic literature review during August, 2011 using PubMed, EMBASE, and Cochrane Library in English and CBMDISK, CNKI, VIP and Wanfang Database in Chinese. We also carried out a search of general and specific hemophilia related websites. Reference lists of key reviews were hand-searched for further relevant research. Studies providing data of the prevalence of hemophilia or its subtypes were included. Meta-analysis was done using the generic inverse variance model. Twenty-two studies were included in the meta-analysis. The overall weighted prevalence of hemophilia was 3.6 per 100,000 and the prevalence among males was 5.5 per 100,000. The prevalence based on community studies was 2.9 per 100,000. The proportions of HA, HB, HC and VWD were 70.97%,16.13%,6.45% and 2.90%, respectively. The prevalences calculated in our study were higher than any previous studies in mainland China, but lower than the world-wide prevalences. The registration rate of hemophiliacs was extremely low. HA and HB were the major subtypes of hemophilia.

Maternal serum neonicotinoids during early-mid pregnancy and congenital heart diseases in offspring: An exploratory study.

Experimental evidence has indicated a correlation between in-utero exposure to neonicotinoid pesticides (NEOs) and adverse birth outcomes in mammals. However, the distribution of NEO exposure during human pregnancy, as well as its association with congenital heart diseases (CHDs), the most common birth defects, are unclear. Our purpose was to explore the distribution of and contributing factors to NEO exposure in pregnant women during early-mid pregnancy and to assess the associations between NEOs and CHDs. This nested case-control study was conducted within an ongoing prospective birth cohort study and enrolled 141 CHD singletons and their 282 individually matched controls. Six "parent" NEOs and three NEO metabolites were measured in maternal serum collected at an average gestational age of 16 weeks, using liquid chromatography-tandem mass spectrometry. Logistic regression was used to quantify the NEOs-CHDs associations and explore potential contributing factors to serum NEO levels in controls. N-desmethyl acetamiprid (N-dm-ACE) and imidacloprid (IMI) were the most frequently detected NEOs, found in 100% and 20% of maternal sera, respectively. We did not find a statistically significant association between total NEOs and overall CHDs. However, there was a trend towards a higher risk of septal defects with greater serum NEOs (ORs ranged from 1.80 to 2.36), especially nitro-containing NEOs represented by IMI. Pregnant women with lower education had elevated serum total NEOs compared to women with higher education (OR = 48.39, 95% CI: 23.48-99.72). Pregnant women were primarily exposed to N-dm-ACE and IMI during early-mid pregnancy. Gestational exposure to NEOs may be associated with an increased risk of septal defects, but the evidence is limited at present. Education is a potential contributing factor to NEO exposure in pregnant women. Larger and more precise studies with longitudinal biospecimen collection, are recommended to validate our exploratory findings.

Modulation of stem cell fate in intestinal homeostasis, injury and repair.

The mammalian intestinal epithelium constitutes the largest barrier against the external environment and makes flexible responses to various types of stimuli. Epithelial cells are fast-renewed to counteract constant damage and disrupted barrier function to maintain their integrity. The homeostatic repair and regeneration of the intestinal epithelium are governed by the Lgr5+ intestinal stem cells (ISCs) located at the base of crypts, which fuel rapid renewal and give rise to the different epithelial cell types. Protracted biological and physicochemical stress may challenge epithelial integrity and the function of ISCs. The field of ISCs is thus of interest for complete mucosal healing, given its relevance to diseases of intestinal injury and inflammation such as inflammatory bowel diseases. Here, we review the current understanding of the signals and mechanisms that control homeostasis and regeneration of the intestinal epithelium. We focus on recent insights into the intrinsic and extrinsic elements involved in the process of intestinal homeostasis, injury, and repair, which fine-tune the balance between self-renewal and cell fate specification in ISCs. Deciphering the regulatory machinery that modulates stem cell fate would aid in the development of novel therapeutics that facilitate mucosal healing and restore epithelial barrier function.

Long-term exposure to particulate matter and COPD mortality: Insights from causal inference methods based on a large population cohort in southern China.

BACKGROUND: Evidence of the association between long-term exposure to particulate matter (PM) and chronic obstructive pulmonary disease (COPD) mortality from large population-based cohort study is limited and often suffers from residual confounding issues with traditional statistical methods. We hereby assessed the casual relationship between long-term PM (PM2.5, PM10 and PM10-2.5) exposure and COPD mortality in a large cohort of Chinese adults using state-of-the-art causal inference approaches. METHODS: A total of 580,757 participants in southern China were enrolled in a prospective cohort study from 2009 to 2015 and followed up until December 2020. Exposures to PM at each residential address were obtained from the Long-term Gap-free High-resolution Air Pollutant Concentration dataset. Marginal structural Cox models were used to investigate the association between COPD mortality and annual average exposure levels of PM exposure. RESULTS: During an average follow-up of 8.0 years, 2250 COPD-related deaths occurred. Under a set of causal inference assumptions, the hazard ratio (HR) for COPD mortality was estimated to be 1.046 (95 % confidence interval: 1.034-1057), 1.037 (1.028-1.047), and 1.032 (1.006-1.058) for each 1-µg/m3 increase in annual average concentrations of PM2.5, PM10, and PM10-2.5 respectively. Additionally, the detrimental effects appeared to be more pronounced among the elderly (age ≥ 65) and inactive participants. The effect estimates of PM2.5, PM10, and PM10-2.5 tend to be greater among participants who were generally exposed to PM10 concentrations below 70 µg/m3 than that among the general population. CONCLUSION: Our results support causal links between long-term PM exposure and COPD mortality, highlighting the urgency for more effective strategies to reduce PM exposure, with particular attention on protecting potentially vulnerable groups.

The complex role of air pollution on the association between greenness and respiratory mortality: Insight from a large cohort, 2009-2020.

BACKGROUND: Although emerging studies have illuminated the protective association between greenness and respiratory mortality, efforts to quantify the potentially complex role of air pollution in the causal pathway are still limited. We aimed to examine the potential roles of air pollution in the causal pathway between greenness and respiratory mortality in China. METHODS: We used data from a community-based prospective cohort of 654,115 participants in southern China (Jan 2009-Dec 2020). We evaluated the greenness exposure as a three-year moving average Normalized Difference Vegetation Index (NDVI) within the 500 m buffer around the residence. Cox proportional hazards model was applied to estimate the association between greenness and respiratory mortality. Causal mediation analysis combined with a four-way dimensional decomposition method was utilized to simultaneously quantify the interaction and mediation role of air pollution including PM2.5, PM10, or NO2 on the greenness-respiratory mortality relationship. FINDINGS: We observed 6954 respiratory deaths during 12 years of follow-up. Increasing NDVI level from the lowest to the highest quartile is associated with a 19 % (95%CI: 13-25 %) reduction in the respiratory mortality risk. For the total protective effect, the proportion attributable to the overall negative interaction between greenness and air pollution (PM2.5, PM10, or NO2) was 2.2 % (1.7-3.2 %), 3.5 % (0.4-3.7 %), or 25.0 % (22.8-27.1 %), respectively. Simultaneously, we estimated 25.5 % (20.1-32.0 %), 49.5 % (32.5-71.9 %), or 1.0 % (0.8-1.2 %) of the total protective association was mediated through a reduction in PM2.5, PM10, or NO2, respectively. INTERPRETATION: Increased greenness exposure mitigated respiratory mortality through both the antagonistic interaction and mediation pathway of air pollution (PM2.5, PM10, or NO2).

Estimating causal links of long-term exposure to particulate matters with all-cause mortality in South China.

BACKGROUND: The association between long-term particulate matter (PM) exposure and all-cause mortality has been well-documented. However, evidence is still limited from high-exposed cohorts, especially for PM1 which is smaller while more toxic than other commonly investigated particles. We aimed to examine the potential casual links of long-term PMs exposure with all-cause mortality in high-exposed areas. METHODS: A total of 580,757 participants in southern China were enrolled during 2009-2015 and followed up to 2020. The annual average concentration of PM1, PM2.5, and PM10 at 1 km2 spatial resolution was assessed for each residential address through validated spatiotemporal models. We used marginal structural Cox models to estimate the PM-mortality associations which were further stratified by sociodemographic, lifestyle factors and general exposure levels. RESULTS: 37,578 deaths were totally identified during averagely 8.0 years of follow-up. Increased exposure to all 3 PM size fractions were significantly associated with increased risk of all-cause mortality, with hazard ratios (HRs) of 1.042 (95 % confidence interval (CI): 1.037-1.046), 1.031 (95 % CI: 1.028-1.033), and 1.029 (95 % CI: 1.027-1.031) per 1 µg/m3 increase in PM1, PM2.5, and PM10 concentrations, respectively. We observed greater effect estimates among the elderly (age ≥ 65 years), unmarried participants, and those with low education attainment. Additionally, the effect of PM1, PM2.5, and PM10 tend to be higher in the low-exposure group than in the general population. CONCLUSIONS: We provided comprehensive evidence for the potential causal links betweenlong-term PM exposureand all-cause mortality, and suggested stronger links for PM1compared to large particles and among certain vulnerable subgroups.

Interactions between long-term ambient particle exposures and lifestyle on the prevalence of hypertension and diabetes: insight from a large community-based survey.

INTRODUCTION: Evidence on the interaction of lifestyle and long-term ambient particle (PM) exposure on the prevalence of hypertension, diabetes, particularly their combined condition is limited. We investigate the associations between PM and these outcomes and whether the associations were modified by various lifestyles. METHODS: This was a large population-based survey during 2019-2021 in Southern China. The concentrations of PM were interpolated and assigned to participants by the residential address. Hypertension and diabetes status were from questionnaires and confirmed with the community health centres. Logistic regression was applied to examine the associations, followed by a comprehensive set of stratified analyses by the lifestyles including diet, smoking, drinking, sleeping and exercise. RESULTS: A total of 82 345 residents were included in the final analyses. For each 1 µg/m3 increase in PM2.5, the adjusted OR for the prevalence of hypertension, diabetes and their combined condition were 1.05 (95% CI 1.05 to 1.06), 1.07 (95% CI 1.06 to 1.08) and 1.05 (95% CI 1.04 to 1.06), respectively. We observed that the association between PM2.5 and the combined condition was greatest in the group with 4-8 unhealthy lifestyles (OR=1.09, 95% CI 1.06 to 1.13) followed by the group with 2-3 and those with 0-1 unhealthy lifestyle (P interaction=0.026). Similar results and trends were observed in PM10 and/or in those with hypertension or diabetes. Individuals who consumed alcohol, had inadequate sleep duration or had poor quality sleep were more vulnerable. CONCLUSION: Long-term PM exposure was associated with increased prevalence of hypertension, diabetes and their combined condition, and those with unhealthy lifestyles suffered greater risks of these conditions.

Identifying joint impacts of sun radiation, temperature, humidity, and rain duration on triggering mental disorders using a high-resolution weather monitoring system.

BACKGROUND: Mental disorders (MDs) are behavioral or mental patterns that cause significant distress or impairment of personal functioning. Previously, temperature has been linked to MDs, but most studies suffered from exposure misclassification due to limited monitoring sites. We aimed to assess whether multiple meteorological factors could jointly trigger MD-related emergency department (ED) visits in warm season, using a highly dense weather monitoring system. METHODS: We conducted a time-stratified, case-crossover study. MDs-related ED visits (primary diagnosis) from May-October 2017-2018 were obtained from New York State (NYS) discharge database. We obtained solar radiation (SR), relative humidity (RH), temperature, heat index (HI), and rainfall from Mesonet, a real-time monitoring system spaced about 17 miles (126 stations) across NYS. We used conditional logistic regression to assess the weather-MD associations. RESULTS: For each interquartile range (IQR) increase, both SR (excess risk (ER): 4.9%, 95% CI: 3.2-6.7%) and RH (ER: 4.0%, 95% CI: 2.6-5.4%) showed the largest risk for MD-related ED visits at lag 0-9 days. While temperature presented a short-term risk (highest ER at lag 0-2 days: 3.7%, 95% CI: 2.5-4.9%), HI increased risk over a two-week period (ER range: 3.7-4.5%), and rainfall hours showed an inverse association with MDs (ER: -0.5%, 95% CI: 0.9-(-0.1)%). Additionally, we observed stronger association of SR, RH, temperature, and HI in September and October. Combination of high SR, RH, and temperature displayed the largest increase in MDs (ER: 7.49%, 95% CI: 3.95-11.15%). The weather-MD association was stronger for psychoactive substance usage, mood disorders, adult behavior disorders, males, Hispanics, African Americans, individuals aged 46-65, or Medicare patients. CONCLUSIONS: Hot and humid weather, especially the joint effect of high sun radiation, temperature and relative humidity showed the highest risk of MD diseases. We found stronger weather-MD associations in summer transitional months, males, and minority groups. These findings also need further confirmation.