Associations of Long-Term Exposure to Fine Particulate Constituents With Cardiovascular Diseases and Underlying Metabolic Mediations: A Prospective Population-Based Cohort in Southwest China.

BACKGROUND: The health effects of particulate matter with an aerodynamic diameter ≤2.5 µm (PM2.5) might differ depending on compositional variations. Little is known about the joint effect of PM2.5 constituents on metabolic syndrome and cardiovascular disease (CVD). This study aims to evaluate the combined associations of PM2.5 components with CVD, identify the most detrimental constituent, and further quantify the mediation effect of metabolic syndrome. METHODS AND RESULTS: A total of 14 427 adults were included in a cohort study in Sichuan, China, and were followed to obtain the diagnosis of CVD until 2021. Metabolic syndrome was defined by the simultaneous occurrence of multiple metabolic disorders measured at baseline. The concentrations of PM2.5 chemical constituents within a 1-km2 grid were derived based on satellite- and ground-based detection methods. Cox proportional hazard models showed that black carbon, organic matter (OM), nitrate, ammonium, chloride, and sulfate were positively associated with CVD risks, with hazard ratios (HRs) ranging from 1.24 to 2.11 (all P<0.05). Quantile g-computation showed positive associations with 4 types of CVD risks (HRs ranging from 1.48 to 2.25, all P<0.05). OM and chloride had maximum weights for CVD risks. Causal mediation analysis showed that the positive association of OM with total CVD was mediated by metabolic syndrome, with a mediation proportion of 1.3% (all P<0.05). CONCLUSIONS: Long-term exposure to PM2.5 chemical constituents is positively associated with CVD risks. OM and chloride appear to play the most responsible role in the positive associations between PM2.5 and CVD. OM is probably associated with CVD through metabolic-related pathways.

Visualization of therapeutic intervention for acute liver injury using low-intensity pulsed ultrasound-responsive phase variant nanoparticles.

Acute liver injury (ALI) is a highly fatal condition characterized by sudden massive necrosis of liver cells, inflammation, and impaired coagulation function. Currently, the primary clinical approach for managing ALI involves symptom management based on the underlying causes. The association between excessive reactive oxygen species originating from macrophages and acute liver injury is noteworthy. Therefore, we designed a novel nanoscale phase variant contrast agent, denoted as PFP@CeO2@Lips, which effectively scavenges reactive oxygen species, and enables visualization through low intensity pulsed ultrasound activation. The efficacy of the nanoparticles in scavenging excess reactive oxygen species from RAW264.7 and protective AML12 cells has been demonstrated through in vitro and in vivo experiments. Additionally, these nanoparticles have shown a protective effect against LPS/D-GalN attack in C57BL/6J mice. Furthermore, when exposed to LIPUS irritation, the nanoparticles undergo liquid-gas phase transition and enable ultrasound imaging.

Mediation of metabolic syndrome in the association between long-term exposure to particulate matter and incident cardiovascular disease: Evidence from a population-based cohort in Chengdu.

BACKGROUND: Particulate matter (PM) exposure has been linked with cardiovascular disease (CVD) and metabolic syndrome (MetS), the latter characterized by concurrent multiple metabolic disorders. As a result, the mechanisms assumption from PM to CVD through MetS have emerged, thus requiring further epidemiological evidence. This cohort study aimed to assess whether MetS mediates the associations of PM with CVD risk. METHODS: This study included 14,195 participants from the Chengdu cohort of the China Multi-Ethnic Cohort (CMEC) study in 2018. The primary outcome of incident CVD diagnoses was identified using matched hospital records from the Health Information Center of Sichuan Province. Residence-specific levels of PM with aerodynamic diameters of ≤ 1 µm (PM1), ≤ 2.5 µm (PM2.5), and ≤ 10 µm (PM10) were estimated by spatiotemporal models. Causal mediation analyses were applied to evaluate the indirect effect of MetS. RESULTS: Increased exposure levels to PM were significantly associated with MetS and CVD. Mediation analyses indicated that the associations between PM exposure and CVD were mediated by MetS, with the proportion of multiple mediations being 19.3%, 12.1%, and 13.5% for PM1, PM2.5, and PM10, respectively. Further moderated mediation analyses suggested that male, overweight individuals, alcohol drinkers, and those suffering from indoor air pollution may experience more significant adverse effects from PM exposure on CVD via MetS than others. CONCLUSIONS: Our findings suggest that MetS partially mediates the association between long-term exposure to PM and CVD. These mediation effects appear to be amplified by demographic characteristics and unhealthy lifestyles.

Long-term exposure to ambient PM2.5 and its constituents is associated with MAFLD.

Background & Aims: Existing evidence suggests that long-term exposure to ambient fine particulate pollution (PM2.5) may increase metabolic dysfunction-associated fatty liver disease (MAFLD) risk. However, there is still limited evidence on the association of PM2.5 constituents with MAFLD. Therefore, this study explores the associations between the five main chemical constituents of PM2.5 and MAFLD to provide more explicit information on the liver exposome. Methods: A total of 76,727 participants derived from the China Multi-Ethnic Cohort, a large-scale epidemic survey in southwest China, were included in this study. Multiple linear regression models were used to estimate the pollutant-specific association with MAFLD. Weighted quantile sum regression was used to evaluate the joint effect of the pollutant-mixture on MAFLD and identify which constituents contribute most to it. Results: Three-year exposure to PM2.5 constituents was associated with a higher MAFLD risk and more severe liver fibrosis. Odds ratios for MAFLD were 1.480, 1.426, 1.294, 1.561, 1.618, and 1.368 per standard deviation increase in PM2.5, black carbon, organic matter, ammonium, sulfate, and nitrate, respectively. Joint exposure to the five major chemical constituents was also positively associated with MAFLD (odds ratio 1.490, 95% CI 1.360-1.632). Nitrate contributed most to the joint effect of the pollutant-mixture. Further stratified analyses indicate that males, current smokers, and individuals with a high-fat diet might be more susceptible to ambient PM2.5 exposure than others. Conclusions: Long-term exposure to PM2.5 and its five major chemical constituents may increase the risk of MAFLD. Nitrate might contribute most to MAFLD, which may provide new clues for liver health. Males, current smokers, and participants with high-fat diets were more susceptible to these associations. Impact and implications: This large-scale epidemiologic study explored the associations between constituents of fine particulate pollution (PM2.5) and metabolic dysfunction-associated fatty liver disease (MAFLD), and further revealed which constituents play a more important role in increasing the risk of MAFLD. In contrast to previous studies that examined the effects of PM2.5 as a whole substance, this study carefully explored the health effects of the individual constituents of PM2.5. These findings could (1) help researchers to identify the specific particles responsible for hepatotoxicity, and (2) indicate possible directions for policymakers to efficiently control ambient air pollution, such as targeting the sources of nitrate pollution.

SHMT as a Potential Therapeutic Target for Renal Cell Carcinoma.

BACKGROUND: Serine hydroxymethyltransferase (SHMT) is a serine-glycine-one-carbon metabolic enzyme in which SHMT1 and SHMT2 encode the cytoplasmic and mitochondrial isoenzymes, respectively. SHMT1 and SHMT2 are key players in cancer metabolic reprogramming, and thus are attractive targets for cancer therapy. However, the role of SHMT in patients with renal cell carcinoma (RCC) has not been fully elucidated. We aimed to systematically analyze the expression, gene regulatory network, prognostic value, and target prediction of SHMT1 and SHMT2 in patients with kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), and kidney renal papillary cell carcinoma (KIRP); elucidate the association between SHMT expression and RCC; and identify potential new targets for clinical RCC treatment. METHODS: Several online databases were used for the analysis, including cBioPortal, TRRUST, GeneMANIA, GEPIA, Metascape, UALCAN, LinkedOmics, and TIMER. RESULTS: SHMT1 and SHMT2 transcript levels were significantly down- and upregulated, respectively, in patients with KICH, KIRC, and KIRP, based on sample type, individual cancer stage, sex, and patient age. Compared to men, women with KIRC and KIRP showed significantly up- and downregulated SHMT1 transcript levels, respectively. However, SHMT2 transcript levels were significantly upregulated in the patients mentioned above. KIRC and KIRP patients with high SHMT1 expression had longer survival periods than those with low SHMT1 expression. In patients with KIRC, the findings were similar to those mentioned above. However, in KICH patients, the findings were the opposite regarding SHMT2 expression. SHMT1 versus SHMT2 were altered by 9% versus 3% (n = 66 KICH patients), 4% versus 4% (n = 446 KIRC patients), and 6% versus 7% (n = 280 KIRP patients). SHMT1 versus SHMT2 promoter methylation levels were significantly up- and downregulated in patients with KIRP versus KIRC and KIRP, respectively. SHMT1, SHMT2, and their neighboring genes (NG) formed a complex network of interactions. The molecular functions of SHMT1 and its NG in patients with KICH, KIRC, and KIRP, included clathrin adaptor, metalloendopeptidase, and GTPase regulator activities; lipid binding, active transmembrane transporter activity, and lipid transporter activity; and type I interferon receptor binding, integrin binding, and protein heterodimerization, respectively. Their respective Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were involved in lysosome activity, human immunodeficiency virus 1 infection, and endocytosis; coronavirus disease 2019 and neurodegeneration pathways (multiple diseases); and RIG-I-like receptor signaling pathway, cell cycle, and actin cytoskeleton regulation. The molecular functions of SHMT2 and its NG in patients with KICH, KIRC, and KIRP included cell adhesion molecule binding and phospholipid binding; protein domain-specific binding, enzyme inhibitor activity, and endopeptidase activity; and hormone activity, integrin binding, and protein kinase regulator activity, respectively. For patients with KIRC versus KIRP, the KEGG pathways were involved in cAMP and calcium signaling pathways versus microRNAs (MiRNAs) in cancer cells and neuroactive ligand-receptor interactions, respectively. We identified the key transcription factors of SHMT1 and its NG. CONCLUSIONS: SHMT1 and SHMT2 expression levels were different in patients with RCC. SHMT1 and SHMT2 may be potential therapeutic and prognostic biomarkers in these patients. Transcription factor (MYC, STAT1, PPARG, AR, SREBF2, and SP3) and miRNA (miR-17-5P, miR-422, miR-492, miR-137, miR-30A-3P, and miR-493) regulations may be important strategies for RCC treatment.

Anemia is associated with long-term exposure to PM2.5 and its components: a large population-based study in Southwest China.

Background: Anemia is linked to PM2.5 (particulate matter with aerodynamic diameters of ⩽2.5 µm) exposure, which can increase the risk of various negative health outcomes. It remains unclear which PM2.5 components are associated with anemia and the respective contribution of each component to this association. Objective: This study aimed at investigating the association between PM2.5 and anemia in the general population and to identify the most critical PM2.5 toxic components in this association. Design: Cross-sectional study. Methods: Our study involved a large cohort of 73,511 individuals aged 30-79 from China's multi-ethnic population. We employed satellite observations and the chemical transport model (GEOS-Chem)to estimate the long-term exposure to PM2.5 and its components. Anemia was defined, according to WHO guidelines, as Hb levels below 130 g/L for men and below 120 g/L for women. Through logistic regression, we investigated the association between PM2.5 components and anemia. By utilizing weighted quantile sum (WQS) analysis, we identified key components and gained insights into their combined impact on anemia. Overall, our study sheds light on the relationship between PM2.5 exposure, its constituents, and the risk of anemia in a large cohort. Results: PM2.5 and three components, nitrate (NIT), organic matter (OM), and soil particles (SOIL), were associated with anemia. Per-standard deviation increase in the 3-year average concentrations of PM2.5 [odds ratio (OR): 1.14, 95% confidence interval (CI): 1.01, 1.28], NIT (1.20, 1.06, 1.35), OM (1.17, 1.04, 1.32), and SOIL (1.22, 1.11, 1.33) were associated with higher odds of anemia. In WQS regression analysis, the WQS index was associated with anemia (OR: 1.29, 95% CI: 1.13, 1.47). SOIL has the highest weight among all PM2.5 components. Conclusions: Long-term exposure to PM2.5 and its constituents is associated with anemia. Moreover, SOIL might be the most critical component of the relationship between PM2.5 and anemia. Our research increases the evidence of the association between PM2.5 and anemia in the general population, and targeted emission control measures should be taken into consideration to mitigate the adverse effects of PM2.5-related anemia.

Long-term exposure to ambient PM2.5 constituents is associated with dyslipidemia in Chinese adults.

BACKGROUND: Ambient particulate matter with aerodynamic diameter ≤ 2.5 µm (PM2.5) consists of various toxic constituents. However, the health effect of PM2.5 may differ depending on its constituents, but the joint effect of PM2.5 constituents remains incompletely understood. OBJECTIVE: Our goal was to evaluate the joint effect of long-term PM2.5 constituent exposures on dyslipidemia and identify the most hazardous chemical constituent. METHODS: This study included 67,015 participants from the China Multi-Ethnic Cohort study. The average yearly levels of PM2.5 constituents for all individuals at their residences were assessed through satellite remote sensing and chemical transport modeling. Dyslipidemia was defined as one or more following abnormal blood lipid concentrations: total cholesterol (TC) ≥ 6.22 mmol/L, triglycerides (TG) ≥ 2.26 mmol/L, high-density lipoprotein cholesterol (HDL-C) < 1.04 mmol/L, and low-density lipoprotein cholesterol (LDL-C) ≥ 4.14 mmol/L. The logistic regression model was utilized to examine the single effect of PM2.5 constituents on dyslipidemia, while the weighted quantile sum regression model for the joint effect. RESULTS: The odds ratio with a 95 % confidence interval for dyslipidemia positively related to per-SD increase in the three-year average was 1.29 (1.20-1.38) for PM2.5 mass, 1.25 (1.17-1.34) for black carbon, 1.24 (1.16-1.33) for ammonium, 1.33 (1.24-1.43) for nitrate, 1.34 (1.25-1.44) for organic matter, 1.15 (1.08-1.23) for sulfate, 1.30 (1.22-1.38) for soil particles, and 1.12 (1.05-1.92) for sea salt. Stronger associations were observed in individuals < 65 years of age, males, and those with low physical activity. Joint exposure to PM2.5 constituents was positively related to dyslipidemia (OR: 1.09, 95 %CI: 1.05-1.14). Nitrate was identified as the constituent with the largest weight (weighted at 0.387). CONCLUSIONS: Long-term exposure to PM2.5 constituents poses a significant risk to dyslipidemia and nitrate might be the most responsible for the risk. These findings indicate that reducing PM2.5 constituent exposures, especially nitrate, could be beneficial to alleviate the burden of disease attributed to PM2.5-related dyslipidemia.

Ambient PM2.5 and its components associated with 10-year atherosclerotic cardiovascular disease risk in Chinese adults.

BACKGROUND: Exposure to particulate matter with aerodynamic diameters less than 2.5 µm (PM2.5) may increase the risk of 10-year atherosclerotic cardiovascular disease (ASCVD) risk. While PM2.5 is comprised of various components, the evidence on the correlation of its components with 10-year ASCVD risk and which component contributes most remains limited. METHODS: Data were derived from the baseline assessments of China Multi-Ethnic Cohort (CMEC). In total, 69,722 individuals aged 35-74 years were included into this study. The annual average concentration of PM2.5 and its components (black carbon, ammonium, nitrate, sulfate, organic matter, soil particles, and sea salt) were estimated by satellite remote sensing and chemical transport models. The ASCVD risk of individuals was calculated by the equations from the China-PAR Project (prediction for ASCVD risk in China). The relationship between single exposure to PM2.5 and its components and predicted 10-year ASCVD risk was assessed using the logistic regression model. The effect of joint exposure was estimated, and the most significant contributor was identified using the weighted quantile sum approach. RESULTS: Totally 69,722 participants were included, of which 95.8 % and 4.2 % had low and high 10-year ASCVD risk, respectively. Per standard deviation increases in the 3-year average concentration of PM2.5 mass (odds ratio [OR] 1.23, 95 % confidence interval [CI]: 1.12-1.35), black carbon (1.21, 1.11-1.33), ammonium (1.21, 1.10-1.32), nitrate (1.25, 1.14-1.38), organic matter (1.29, 1.18-1.42), sulfate (1.17, 1.07-1.28), and soil particles (1.15, 1.04-1.26) were related to high 10-year ASCVD risk. The overall effect (1.19, 1.11-1.28) of the PM2.5 components was positively associated with 10-year ASCVD risk, and organic matter had the most contribution to this relationship. Female participants were more significantly impacted by PM2.5, black carbon, ammonium, nitrate, organic matter, sulfate, and soil particles compared to others. CONCLUSION: Long-term exposure to PM2.5 mass, black carbon, ammonium, nitrate, organic matter, sulfate, and soil particles were positively associated with high 10-year ASCVD risk, while sea salt exhibited a protective effect. Moreover, the organic matter might take primary responsibility for the relationship between PM2.5 and 10-year ASCVD risk. Females were more susceptible to the adverse effect.

The association between chemical constituents of ambient fine particulate matter and obesity in adults: A large population-based cohort study.

OBJECTIVES: Current evidence demonstrated that ambient fine particulate matter with an aerodynamic diameter ≤2.5 µm (PM2.5) and its constituents may be obesogenic in children, but evidence from adults is lacking. Our aim was to characterize the association between PM2.5 and its constituents and obesity in adults. METHODS: We included 68,914 participants from the China Multi-Ethnic Cohort (CMEC) baseline survey. Three-year average concentrations of PM2.5 and its constituents were evaluated by linking pollutant estimates to the geocoded residential addresses. Obesity was defined as body mass index (BMI) ≥ 28 kg/m2. Logistic regression was used to examine the relationship between PM2.5 and its constituents and obesity. We performed weighed quantile sum (WQS) regression to get the overall effect of PM2.5 and its constituents and the relative contribution of each constituent. RESULTS: Per-SD increase in PM2.5 (odds ratio [OR] = 1.43, 95% confidence interval [CI]: 1.37-1.49), black carbon (BC) (1.42, 1.36-1.48), ammonium (1.43, 1.37-1.49), nitrate (1.44, 1.38-1.50), organic matter (OM) (1.45, 1.39-1.51), sulfate (1.42, 1.35-1.48), and soil particles (SOIL) (1.31, 1.27-1.36) were positively associated with obesity, and SS (0.60, 0.55-0.65) was negatively associated with obesity. The overall effect (OR = 1.34, 95% CI: 1.29-1.41) of the PM2.5 and its constituents was positively associated with obesity, and ammonium made the most contribution to this relationship. Participants who were older, female, never smoked, lived in urban areas, had lower income or higher levels of physical activity were more significantly adversely affected by PM2.5, BC, ammonium, nitrate, OM, sulfate and SOIL compared to other individuals. CONCLUSION: Our study revealed that PM2.5 constituents except SS were positively associated with obesity, and ammonium played the most important role. These findings provided new evidence for public health interventions, especially the precise prevention and control of obesity.

Bayesian borrowing from historical control data in a vaccine efficacy trial.

In the context of vaccine efficacy trial where the incidence rate is very low and a very large sample size is usually expected, incorporating historical data into a new trial is extremely attractive to reduce sample size and increase estimation precision. Nevertheless, for some infectious diseases, seasonal change in incidence rates poses a huge challenge in borrowing historical data and a critical question is how to properly take advantage of historical data borrowing with acceptable tolerance to between-trials heterogeneity commonly from seasonal disease transmission. In this article, we extend a probability-based power prior which determines the amount of information to be borrowed based on the agreement between the historical and current data, to make it applicable for either a single or multiple historical trials available, with constraint on the amount of historical information to be borrowed. Simulations are conducted to compare the performance of the proposed method with other methods including modified power prior (MPP), meta-analytic-predictive (MAP) prior and the commensurate prior methods. Furthermore, we illustrate the application of the proposed method for trial design in a practical setting.

Examining clinical capability of township healthcare centres for rural health service planning in Sichuan, China: an administrative data analysis.

OBJECTIVE: This study aimed to examine the clinical capability of township healthcare centres (THCs), the main primary care providers in rural China, as a basis for rural health service planning. DESIGN: Observational study of quantitative analysis using administrative data. SETTING: Three counties with low, middle and high social economic development level, respectively, in Sichuan province western China. PARTICIPANTS: 9 THCs and 6 county hospitals (CHs) were purposively selected in the three counties. Summary of electronic medical records of 31 633 admissions from 1 January 2015 to 30 December 2015 of these selected health institutions was obtained from the Health Information Centre of Sichuan province. MAIN OUTCOME MEASURES: Six indicators in scope of inpatient services related to diseases and surgeries in the THCs as proxy of clinical capability, were compared against national standard of capability building of THCs, among counties, and between THCs and CHs of each county. RESULTS: The clinical capability of THCs was suboptimal against the national standard, though that of the middle-developed county was better than that in the rich and the poor counties. THCs mainly provided services of infectious or inflammatory diseases, of respiratory and digestive systems, but lacked clinical services related to injuries, poisoning, pregnancy, childbirth and surgeries. A large proportion of the top 20 diseases of inpatients were potentially avoidable hospitalisations (PAHs) and were overlapped between THCs and CHs. CONCLUSIONS: The clinical capability of THCs was generally suboptimal against national standard. It may be affected by the economics, population size, facilities, workforce and the share of services of THCs in local health systems. Identification of absent services and PAHs may help to identify development priorities of local THCs. Clarification of the roles of THCs and CHs in the tiered rural health system in China is warranted to develop a better integrated health system.

Systematic analysis of the BET family in adrenocortical carcinoma: The expression, prognosis, gene regulation network, and regulation targets.

Background: Bromodomain and extracellular terminal (BET) family (including BRD2, BRD3, and BRD4) is considered to be a major driver of cancer cell growth and a new target for cancer therapy. Currently, more than 30 targeted inhibitors have shown significant inhibitory effects against various tumors in preclinical and clinical trials. However, the expression levels, gene regulatory networks, prognostic value, and target prediction of BRD2, BRD3, and BRD4 in adrenocortical carcinoma (ACC) have not been fully elucidated. Therefore, this study aimed to systematically analyze the expression, gene regulatory network, prognostic value, and target prediction of BRD2, BRD3, and BRD4 in patients with ACC, and elucidated the association between BET family expression and ACC. We also provided useful information on BRD2, BRD3, and BRD4 and potential new targets for the clinical treatment of ACC. Methods: We systematically analyzed the expression, prognosis, gene regulatory network, and regulatory targets of BRD2, BRD3, and BRD4 in ACC using multiple online databases, including cBioPortal, TRRUST, GeneMANIA, GEPIA, Metascape, UALCAN, LinkedOmics, and TIMER. Results: The expression levels of BRD3 and BRD4 were significantly upregulated in ACC patients at different cancer stages. Moreover, the expression of BRD4 was significantly correlated with the pathological stage of ACC. ACC patients with low BRD2, BRD3, and BRD4 expressions had longer survival than patients with high BRD2, BRD3, and BRD4 expressions. The expression of BRD2, BRD3, and BRD4 was altered by 5%, 5%, and 12% in 75 ACC patients, respectively. The frequency of gene alterations in the 50 most frequently altered BRD2, BRD3, and BRD4 neighboring genes in these ACC patients were ≥25.00%, ≥25.00%, and ≥44.44%, respectively. BRD2, BRD3, and BRD4 and their neighboring genes form a complex network of interactions mainly through co-expression, physical interactions, and shared protein domains. Molecular functions related to BRD2, BRD3, and BRD4 and their neighboring genes mainly include protein-macromolecule adaptor activity, cell adhesion molecule binding, and aromatase activity. Chemokine signaling pathway, thiamine metabolism, and olfactory transduction were found to be enriched as per the KEGG pathway analysis. SP1, NPM1, STAT3, and TP53 are key transcription factors for BRD2, BRD4, and their neighboring genes. MiR-142-3P, miR-484, and miR-519C were the main miRNA targets of BRD2, BRD3, BRD4, and their neighboring genes. We analyzed the mRNA sequencing data from 79 patients with ACC and found that ZSCAN12, DHX16, PRPF4B, EHMT1, CDK5RAP2, POMT1, WIZ, ZNF543, and AKAP8 were the top nine genes whose expression were positively associated with BRD2, BRD3, and BRD4 expression. The expression level of BRD2, BRD3, and BRD4 positively correlated with B cell and dendritic cell infiltration levels. BRD4-targeted drug PFI-1 and (BRD2, BRD3, and BRD4)-targeted drug I-BET-151 may have good inhibitory effects on the SW13 cell line. Conclusions: The findings of this study provide a partial basis for the role of BRD2, BRD3, and BRD4 in the occurrence and development of ACC. In addition, this study also provides new potential therapeutic targets for ACC, which can serve as a reference for future basic and clinical research.

[Ethnic differences in influencing factors of caregivers' first complementary food addition behavior in western rural areas].

OBJECTIVE: To investigate the status quo and influencing factors of the first-time complementary food addition behavior of caregivers in the multi-ethnic background in the western rural areas. METHODS: In 2019, a multi-stage stratified cluster random sampling was used to selecting research subjects in western rural areas. A structured questionnaire was designed by ourselves with literature review and expert consultation method, and information such as sociodemographic characteristics, feeding knowledge, and complementary food addition of 1290 caregivers and infants were collected, ordered multi-classification Logistic regression was used to analyze the influencing factors of the first complementary food addition behavior of the Han nationality and the minority nationality. RESULTS: In the western rural areas, only 8.22% of the caregivers had better behavior of first complementary food addition, and 16.31% of the caregivers in the Han group had a good behavior of first complementary food addition. In the minority population, only 3.64% of infant caregivers had a good behavior of first complementary food addition. In Han, parents, as caregivers, had better first complementary food addition behavior than grandparents(OR=1.7829, 95% CI 1.1651-2.7283). Among ethnic minorities, education(OR=1.753, 95%CI 1.190-2.581), family fixed assets(OR=3.870, 95%CI 1.959-7.645)and feeding knowledge(OR=3.396, 95%CI 2.749-4.195) were the promoting factors for the first complementary food addition behavior. CONCLUSION: In western rural areas, caregivers' behavior of adding complementary food for the first time is generally poor.

[Association of Dietary Diversity with Growth and Development of Children in Multi-ethnic Rural Areas of Sichuan Province].

Objective To understand the growth and dietary diversity status of children in multi-ethnic areas of Sichuan province,and to explore the associations of dietary diversity with growth and development indicators. Methods Children of 18-36 months old and their primary caregivers were selected with multi-stage cluster random sampling method from rural areas of Han,Tibetan,and Yi ethnic groups in Sichuan province. The sociodemographic information of children and their caregivers was collected using self-designed questionnaire.The dietary diversity score(DDS)was calculated according to the criteria in the Guidelines for Measuring Household and Individual Dietary Diversity released by the Food and Agriculture Organization of the United Nations.The body height(length)and body weight of each child were measured by standard equipment for anthropological measurement,and the height for age Z score(HAZ),weight for age Z score(WAZ),and weight for height Z score(WHZ) were calculated.Multivariate linear regression was performed to analyze the relationship between dietary diversity and growth indicators of children. Results A total of 1092 children were enrolled in this study,and the prevalence of stunting(HAZ<-2),underweight(WAZ<-2),and wasting(WHZ<-2)was 21.1%,4.9%,and 2.5%,respectively.The children had the mean DDS of 4.8±1.7,and 45.3% of children had poor dietary diversity(DDS≤4).The children of Han ethnic group(5.8±1.4)had higher DDS than those of Tibetan ethnic group(4.9±1.6)and Yi ethnic group(3.9±1.6)(P<0.001).The results of multivariate linear regression indicated that DDS was positively correlated with HAZ(ß=0.206,95%CI=0.158-0.254,P<0.001)after adjustment of sex,age,birth weight,preterm birth,and parental body height.After further adjustment of family fixed assets,ethnic group,caregiver's type,and caregiver's education background,the correlation between DDS and HAZ remained significant(ß=0.077,95%CI=0.026-0.128, P=0.003). Conclusions The children in the multi-ethnic rural areas of Sichuan province showed troublesome growth and development status and low dietary diversity,which were conspicuously different between ethnic groups,especially in the rural areas of Yi ethnic group.The dietary diversity was positively associated with HAZ.It is recommended to carry out nutrition and health education according to the local dietary characteristics and thus improve the growth and development of children in multi-ethnic rural areas in Sichuan.

Identification of the susceptible subpopulations for wide pulse pressure under long-term exposure to ambient particulate matters.

Wide pulse pressure (WPP) is a preclinical indicator for arterial stiffness and cardiovascular diseases. Long-term exposure to ambient particulate matters (PMs) would increase the risk of WPP. Although reducing pollutants emissions and avoiding outdoor activity during a polluted period are effective ways to blunt the adverse effects. Identifying and protecting the susceptible subpopulation is another crucial way to reduce the disease burdens. Therefore, we aimed to identify the susceptible subpopulations of WPP under long-term exposure to PMs. The WPP was defined as pulse pressure over 60 mmHg. Three-year averages of PMs were estimated using random forest approaches. Associations between WPP and PMs exposure were estimated using generalized propensity score weighted logistic regressions. Demographic, socioeconomic characteristics, health-related behaviors, and hematological biomarkers were collected to detect the modification effects on the WPP-PMs associations. Susceptible subpopulations were defined as those with significantly higher risks of WPP under PMs exposures. The PMs-WPP associations were significant with ORs (95%CI) of 1.126 (1.094, 1.159) for PM1, 1.174 (1.140, 1.210) for PM2.5, and 1.111 (1.088, 1.135) for PM10. There were 17 subpopulations more sensitive to WPP under long-term exposure to PMs. The susceptibility was higher in subpopulations with high BMI (Q3-Q4 quartiles), high-intensive physical activity (Q3 or Q4 quartile), insufficient or excessive fruit intake (Q1 or Q5 quartile), insufficient or too long sleep length (<7 or >8 h). Subpopulations with elevated inflammation markers (WBC, LYM, BAS, EOS: Q3-Q4 quartiles) and glucose metabolism indicators (HbA1c, GLU: Q3-Q4 quartiles) were more susceptible. Besides, elder, urban living, low socioeconomic level, and excessive red meat and sodium salt intake were also related to higher susceptibility. Our findings on the susceptibility characteristics would help to develop more targeted disease prevention and therapy strategies. Health resources can be allocated more effectively by putting more consideration to subpopulations with higher susceptibility.

Extending the two-stage single arm phase II clinical trial design to the delayed response scenario.

Two-stage single arm designs are widely used in phase II clinical trials with binary endpoints. The trial may be stopped early due to insufficient positive responses in the first stage. There may be some enrolled subjects who have yet to respond by the end of the first stage, and their data are ignored if the first stage results in rejection of the trial. It is possible that the result after the first stage is rejection by a slim margin, while the results of pipeline subjects are quite positive. In this case, combining the data from the two sources may provide a valuable opportunity to rescue a promising treatment that was mistakenly rejected. We propose a novel double-check design to take advantage of the pipeline subjects' data to establish a rescue criterion based on two-stage design. When the rescue criterion is met, the decision to reject the trial at the end of the first stage can be reversed, allowing the trial to continue. A derivation based on a binomial distribution shows that the double-check strategy can strictly preserve the type I error rate. Further examination shows that the strategy can provide a slight increase in overall power and a substantial increase in conditional power when the proportion of positive response at the end of the first stage is at the margin. The extra rescue opportunity's cost is pretty low, only a slight increasing in the expected sample size.

PYCR in Kidney Renal Papillary Cell Carcinoma: Expression, Prognosis, Gene Regulation Network, and Regulation Targets.

BACKGROUND: Pyrroline-5-carboxylate reductase (PYCR) includes three human genes encoding three isozymes, PYCR1, PYCR2, and PYCR3 (or PYCRL), which facilitate the final step in the conversion of glutamine to proline. These genes play important roles in regulating the cell cycle and redox homeostasis as well as promoting growth signaling pathways. Proline is abnormally upregulated in a variety of cancers, and as the last key enzyme in proline production, PYCR plays an integral role in promoting tumorigenesis and cancer progression. However, its role in patients with kidney renal papillary cell carcinoma (KIRP) has not been fully elucidated. In this study, we aimed to systematically analyze the expression, gene regulatory network, prognostic value, and target prediction of PYCR in patients with KIRP, elucidate the association between PYCR expression and KIRP, and identify potential new targets for the clinical treatment of KIRP. METHODS: We systematically analyzed the expression, prognosis, gene regulatory network, and regulatory targets of PYCR1, PYCR2, and PYCRL in KIRP using multiple online databases including cBioPortal, STRING, MethSurv, GeneMANIA, Gene Expression Profiling Interactive Analysis (GEPIA), Metascape, UALCAN, LinkedOmics, and TIMER. RESULTS: The expression levels of PYCR1, PYCR2, and PYCRL were considerably upregulated in patients with KIRP based on sample type, sex, age, and individual cancer stage. PYCR1 and PYCR2 transcript levels were markedly upregulated in females than in males, and patients aged 21-40 years had higher PYCR1 and PYCR2 transcript levels than those in other age groups. Interestingly, PYCR2 transcript levels gradually decreased with age. In addition, the expressions of PYCR1 and PYCR2 were notably correlated with the pathological stage of KIRP. Patients with KIRP with low PYCR1 and PYCR2 expression had longer survival than those with high PYCR1 and PYCR2 expression. PYCR1, PYCR2, and PYCRL were altered by 4%, 7%, and 6%, respectively, in 280 patients with KIRP. The methylation levels of cytosine-phosphate-guanine (CpG) sites in PYCR were markedly correlated with the prognosis of patients with KIRP. PYCR1, PYCR2, PYCRL, and their neighboring genes form a complex network of interactions. The molecular functions of the genes, as demonstrated by their corresponding Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, included calcium channel activity, phospholipid binding, RNA polymerase II-specificity, and kinase and GTPase-regulatory activities. PYCR1, PYCR2, and PYCRL targeted miR-21, miR-221, and miR-222, resulting in a better prognosis of KIRP. We analyzed mRNA sequencing data from 290 patients with KIRP and found that ADA, NPM3, and TKT were positively associated with PYCR1 expression; PFDN2, JTB, and HAX1 were positively correlated with PYCR2 expression; SHARPIN, YDJC, and NUBP2 were positively correlated with PYCRL expression; PYCR1 was positively correlated with B cell and CD8+ T-cell infiltration levels; macrophage infiltration was negatively correlated with PYCR2 expression; and PYCRL expression was negatively correlated with B-cell, CD8+ T cell, and dendritic cell infiltration levels. CONCLUSIONS: PYCR1, PYCR2, and PYCRL may be potential therapeutic and prognostic biomarkers for patients with KIRP. The regulation of microRNAs (miRNAs), including miR-21, miR-221, and miR-222, may prove an important strategy for KIRP treatment.

Mediating Effect of Work Stress on the Associations Between Psychological Job Demands, Social Approval, and Workplace Violence Among Health Care Workers in Sichuan Province of China.

Objective: The aim of this study was to investigate the prevalence of workplace violence against health care workers, to explore the combined association of work stress, psychological job demands, and social approval with workplace violence and their respective mechanisms among health care workers. Methods: Using data from the Chinese Sixth National Health Service Survey (NHSS) in 2018 conducted among 1,371 health care workers in Sichuan province of China. A self-administered structured questionnaire was used to collect data on health care workers' socio-demographic and work-related characteristics, work stress, psychological job demands, social approval, and workplace violence. We used structural equation modeling (SEM) to test the hypothesized relationship among the variables. Results: The results showed that a total of 77.0% health care workers were exposed to workplace violence. Work stress was directly related to workplace violence (ß = 2.167, 95%CI: 1.707, 2.627), while psychological job demands and social approval had indirect associations with workplace violence via work stress [ß = 0.427, 95%CI: 0.297, 0.557; ß = -0.787, 95%CI: (-0.941)-(-0.633)]. Both psychological job demands (ß = 0.197, 95%CI: 0.139, 0.255) and social approval [ß = -0.346, 95%CI: (-0.399)-(-0.294)] had direct associations with work stress, while social approval had direct association with psychological job demands [ß = -0.085, 95%CI: (-0.136)-(-0.034)]. Psychological job demands mediated the relationship between social approval and work stress. Conclusion: Overall, decreasing workplace violence among health care workers requires to promote interventions to reduce work stress and psychological job demands by improving social approval.

Estimation of ambient PM2.5-related mortality burden in China by 2030 under climate and population change scenarios: A modeling study.

BACKGROUND: Fine particulate matter (PM2.5) pollution is one of the most critical environmental and public health problems in China and has caused an enormous disease burden, especially long-term PM2.5 exposure. Global climate change represents another environmental challenge in the coming decades and is also an essential factor affecting PM2.5 pollution. Moreover, China has an aging population with a changing population size and falling age-standardized mortality rates. However, little evidence exists evaluating the potential impacts from climate change and population aging on the long-term PM2.5 exposure-related disease burden. This study quantifies the impacts of climate and population changes on changes in the disease burden attributed to long-term PM2.5 exposure from 2015 to 2030 in mainland China, which could add evidence for the revision of relevant environmental standards and health policies. METHODS: This modeling study investigated long-term PM2.5 exposure-related mortality across China based on PM2.5 projections under Intergovernmental Panel on Climate Change Representative Concentration Pathways (RCPs) and population scenarios from shared socioeconomic pathways (SSPs). PM2.5 concentrations were simulated by the Weather Research and Forecasting (WRF) and Community Multiscale Air Quality (CMAQ) modeling systems. In addition, three types of population projections in 2030 relative to 2015 were set up as follows: (i) the population remained the same as that in 2015; (ii) the population size changed under SSPs, but the age structure remained the same; (iii) both the population size and age structure changed under SSPs. The global exposure mortality model (GEMM) was adopted to estimate PM2.5-related premature deaths. RESULTS: Ambient PM2.5 concentrations decreased from 2015 to 2030 under the two climate and emission scenarios. Estimates of related premature mortality in 2030 declined compared with that in 2015 due to lower PM2.5 concentrations (RCP4.5: -16.8%; RCP8.5: -16.4%). If the age structure of the population remained unchanged and the population size changed under SSPs, the nonaccidental premature mortality also showed a decrease ranging from -18.6% to -14.9%. When both population size and age structure changed under SSPs, the population in China would become older. Nonaccidental premature mortality would sharply increase by 35.7-52.3% (with a net increase of 666-977 thousand) in 2030. CONCLUSION: The PM2.5 pollution in 2030 under both RCP4.5 and RCP8.5 would slightly improve. The population sizes in 2030 projected by SSPs are relatively stable compared with that in 2015. However, the modest decrease due to air pollution improvement and stable population size would be offset by population aging.

Spatiotemporal assessment of health burden and economic losses attributable to short-term exposure to ground-level ozone during 2015-2018 in China.

BACKGROUND: Ground-level ozone (O3) pollution is currently the one of the severe environmental problems in China. Although existing studies have quantified the O3-related health impact and economic loss, few have focused on the acute health effects of short-term exposure to O3 and have been limited to a single temporal and spatial dimension. METHODS: Based on the O3 concentration obtained from ground monitoring networks in 334 Chinese cities in 2015-2018, this study used a two-stage exposure parameter weighted Log-linear exposure-response function to estimate the cause-specific mortality for short-term exposure to O3. RESULTS: The value of statistical life (VSL) method that were used to calculate the economic loss at the city-level. Our results show that in China, the national all-cause mortality attributed to O3 was 0.27(95% CI: 0.14-0.55) to 0.39 (95% CI: 0.20-0.67) million across 2015-2018. The estimated economic loss caused by O3 was 387.76 (95% CI: 195.99-904.50) to 594.08 (95% CI: 303.34-1140.65) billion CNY, accounting for 0.52 to 0.69% of total reported GDP. Overall, the O3 attributed health and economic burden has begun to decline in China since 2017. However, highly polluted areas still face severe burden, and undeveloped areas suffer from high GDP losses. CONCLUSIONS: There are substantial health impacts and economic losses related to short-term O3 exposure in China. The government should pay attention to the emerging ozone pollution, and continue to strengthen the intervention in traditional priority areas while solving the pollution problem in non-priority areas.