The precise manifestations of iron (Fe) imbalance, especially Fe2+ deficiency, are critical for addressing the health effects of ambient fine particulate matter (PM2.5) on human health. This study integrates epidemiological and in vitro and in vivo evidence to elucidate the role of Fe homeostasis in the effects of PM2.5 exposure on lung injury. Serum was collected from 35 women from Hebei Province, North China, and their residential PM2.5 concentrations were monitored from January 2015 to January 2016. We found that the ferritin light chain (FTL) in serum was positively associated with the PM2.5 concentration, suggesting that PM2.5 disrupts Fe homeostasis in the human body. Intratracheal instillation of naphthalene-1,4-dione-coated black carbon (1,4-NQ-BC), a PM2.5 analogue, increased FTL, but impaired the autophagy flux in rat lungs. 1,4-NQ-BC reduced Fe2+, but increased total Fe in RAW264.7 cells, when there was unimpaired Fe transportation through cell membranes. Likewise, 1,4-NQ-BC activated autophagy, but impaired lysosomal function, consequently inhibiting the autophagic flux in RAW264.7 cells. The role of lysosome dysfunction in PM-induced Fe2+ deficiency was revealed for the first time, via overexpression of transcription factor EB in a RAW264.7 cell model. We concluded that lysosomal damage-evoked Fe2+ deficiency provided sensitive biomarkers and potential therapeutic targets in pulmonary injury associated with ambient PM2.5 exposure.

Primary health care (PHC) is central to achieving universal health coverage, yet longitudinal assessments of residents’ experiences—especially regarding urban–suburban disparities—remain scarce. This study aims to examine changes in PHC service experiences among Shanghai residents between 2023 and 2024, identify urban–suburban differences, and explore key influencing factors. A two-wave cross-sectional survey was conducted at 248 community health centers in Shanghai from May to June in 2023 and 2024. The Chinese version of the Primary Care Assessment Tool–Adult Short Version (PCAT-AS) was used. Propensity score matching ensured comparability between survey waves. Descriptive statistics, hypothesis testing, and multiple linear regression were employed to assess temporal changes, regional disparities, and associated predictors. Residents reported significantly improved PHC experiences in 2024 across all domains (P < 0.001), with the largest gains in service comprehensiveness (+ 0.23) and referral coordination (+ 0.18). Urban residents consistently reported better experiences in continuity, service delivery, and cultural competence, while suburban residents rated higher in first-contact accessibility and service availability. Improvements from 2023 to 2024 were most notable in first-contact accessibility (Δ = +0.11) and comprehensiveness (Δ = +0.10), though domains such as family-centeredness and cultural competence showed limited progress (Δ = +0.01). Multivariate analyses identified residential location, chronic disease burden, psychological distress, and self-rated health as significant predictors of overall PCAT scores. Suburban residence was associated with lower scores (B = − 1.59, P < 0.001), while comorbidities (B = 1.94, P < 0.001) and psychological distress (B = 2.06, P < 0.001) were linked to higher scores. This study demonstrates that while overall perceptions of PHC services among permanent residents in Shanghai improved significantly compared to the previous year—particularly in terms of service comprehensiveness and referral coordination—urban–suburban disparities persist. Specifically, urban residents reported more favorable experiences in first-contact utilization, continuity of care, and cultural competence, whereas suburban residents expressed better perceptions of first-contact accessibility and service availability. Notably, the urban–suburban gaps in first-contact accessibility and service comprehensiveness narrowed between 2023 and 2024, suggesting a positive trajectory toward greater equity in basic health service delivery. Multivariate regression analysis further indicated that residential location, chronic disease burden, psychological distress, and self-rated health status were significant determinants of residents’ PHC experiences. Based on these findings, we recommend the implementation of more targeted interventions focusing on enhancing continuity of care and strengthening integrated management for both mental health and chronic conditions. Special attention should be given to addressing structural disparities between urban and suburban areas and to meeting the health service needs of priority populations, in order to continuously advance both equity and quality in PHC delivery.

In the context of China’s health reforms aimed at strengthening primary care through the Family Doctor Contract Service Program, effectively measuring its functional features is paramount. This study seeks to translate, adapt, and validate the Person-Centered Primary Care Measure (PCPCM) for primary care patients enrolled in family doctor contract services in mainland China. Following the guidelines by Sousa and Rojjanasrirat, we translated and adapted the PCPCM into Simplified Chinese and evaluated its psychometric properties. A total of 583 patients enrolled in family doctor contract services from 10 primary care facilities in Shanghai, China, participated in the study. We assessed the structural validity, internal consistency, stability reliability, and criterion validity of the PCPCM-Simplified Chinese version in accordance with the practical guidelines developed by the Core Outcome Measures in Effectiveness Trials (COMET) initiative and the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) initiative. The study led to the development of the PCPCM-Simplified Chinese version tailored for patients receiving family doctor contract services (PCPCM-SC-FDCS), specifically designed to address the needs of populations most closely aligned with the concept of “primary care patients” in mainland China. Initial pilot testing prompted refinements to enhance clarity and applicability, particularly for Item 5 (Relationship). Analyses of the refined PCPCM-SC-FDCS, based on a three-point Likert scale, revealed that structural validity, internal consistency, and criterion validity all met the criteria for good measurement properties outlined in the relevant guidelines. However, for test-retest reliability, the intraclass correlation coefficient (ICC) between the first and second surveys was 0.58, which fell short of the recommended threshold of ≥ 0.70. The PCPCM-SC-FDCS demonstrates satisfactory reliability and strong feasibility as a tool for evaluating the functional features of primary care among Family Doctor Contract Service Program patients in mainland China. Although further testing and refinement are necessary, this instrument offers a feasible and straightforward approach to evaluating service quality, supporting family doctor teams in enhancing primary care delivery.

Globally, primary care (PC) features like accessibility, continuity, and coordination enhance health outcomes. In China, 940,000 public facilities delivered 4.266 billion PC visits in 2022 (50.68% of total visits), focusing on chronic disease management and public health. Unlike Western gatekeeper models, China’s PC lacks this structure, influencing its characteristics and effectiveness. This review synthesises China’s PC functional features and their relationship with health service outcomes since 2009, combining quantitative and qualitative evidence. Using the JBI mixed-methods framework, we will search PubMed, Embase, Web of Science, Google Scholar, CNKI, and Wanfang Data for studies (quantitative, qualitative, mixed-methods). Two reviewers will screen and assess quality with JBI tools (>50% threshold). A convergent segregated approach integrates quantitative data (feature strength, associations with outcomes) with qualitative insights (stakeholder views on features and effects). This review may shed light on the functional features of China’s primary care system and their relationship with health service outcomes. The synthesized evidence could inform clinical practice, health service delivery, and health policy regarding the health service process of primary care in China, while also identifying areas for future research.

Background: Practice-Based Research Networks (PBRNs) enable collaborative primary care research. In China, since 2023, healthcare reforms emphasizing community-based primary care have spurred PBRN development. However, the research environment and incentives for primary care practitioners (PCPs) to belong to these networks remain under-explored. Objective: This study investigates the research environment and support needed by PCPs in the Shanghai General Practice Research Network (SGPRN) to maximize PBRN development in China. Methods: This study employed a mixed-methods explanatory sequential design. The quantitative component involved an online survey of 145 PCPs from the SGPRN, selected through purposive sampling, who expressed interest in research activities. The survey collected data on their background, research capabilities, research environment, and preferred incentives for participating in PBRN-organized research. Descriptive statistical analysis and the Kano Model were used to analyze and categorize the data. The qualitative component involved one focus group discussion and 21 semi-structured interviews with 24 PCPs from the survey sample, selected to validate and complement the quantitative findings. Interview data were analyzed iteratively using a qualitative descriptive approach. Quantitative and qualitative data were integrated through joint display and meta-synthesis. Results: Most PCPs (85 %) reported a supportive research environment, with 69 % integrating research with clinical practice. However, only 43 % had sufficient research time, and 50 % access to collaborators. Qualitative findings revealed limited professional support and fragmented time as key barriers. Incentives required included opportunities to acquire research skills, leading personally relevant studies, securing primary authorship, and accessing shared data, all contingent on transparent collaboration and trust. All these preferences aligned with institutional performance-driven policies. Conclusion: The SGPRN research environment is currently neutral to slightly favorable, strongly driven by performance-oriented policies. PCPs participate in PBRN research primarily to enhance their research expertise and achieve publication-driven career advancement. Despite these motivations, China’s PBRNs need to draw on international strategies, enhancing research training, fostering collaborative platforms, and prioritizing practice-oriented, high-quality research to improve patient care, while aligning with local general practitioners’ professional aspirations for advancing the discipline and clinical practice, to reconcile and overcome the limitations of output-focused, impractical research policies.

Background Basic medical service is the primary manifestation of primary care within China's healthcare system. Since the 2009 healthcare reform, the theory of primary care functional features has been introduced to China. Chinese researchers have since employed international instruments and developed localized tools to evaluate the process quality of these services across diverse regions and populations. This mixed-methods systematic review aims to synthesize qualitative and quantitative evidence regarding the conceptual connotations, intensity levels, and relationships with health service outcomes of different functional features in China's primary care services. Methods Following the JBI mixed-methods systematic review framework, we searched six databases (PubMed, Embase, Web of Science, Google Scholar, CNKI, and Wanfang) for qualitative, quantitative, and mixed-methods studies published between January 2009 and March 2025. Two reviewers screened literature using Rayyan and assessed methodological quality using JBI tools. Utilizing a convergent segregated approach, we synthesized the qualitative and quantitative findings separately, and subsequently integrated them to explain the pathways and mechanisms underlying the associations between functional features and health service outcomes. Results The review included 60 studies (52 quantitative studies, 4 qualitative studies, and 3 mixed-methods studies). The functional features of China’s primary care services can be broadly categorized into six core dimensions: First Contact, Accessibility, Comprehensiveness, Continuity, Coordination, and Patient Empowerment. Their local conceptual connotations have undergone significant reconfiguration compared to the original theoretical constructs. Overall, the intensity level of these features is medium-to-high. Stronger measurement levels are positively associated with multiple critical health service outcomes, including improved patient health status, enhanced patient experience, lower healthcare costs, preference for primary care first-contact, and reduced general hospital utilization. Furthermore, clear mechanistic pathways influencing key outcomes were identified for the first five features. Conclusion This review validates the real-world value of sustained investment by the Chinese government and society in primary healthcare reform. It supports the strategic enhancement of these functional features to maximize their capacity to improve health outcomes. Finally, it highlights the imperative for future research to employ broader, deeper, and more precise methodologies to capture the evolving nature of primary care in China.

Numerous reports indicated that particulate matter (PM) 2.5 could influence mitochondrion function and disrupt iron homeostasis. Many existing studies predominantly emphasize the role of iron overload (Fe3 +/Fe2+ accumulation) on the damage of mitochondria. But whether the PM could induce iron deficiency or not and related dysfunction remain unclear. Current related clues suggest those need to be investigated. In this study, we employed naphthalene-1,4-dione (1,4 NQ) coated black carbon (BC) as a PM2.5 surrogate to reveal the role of Fe2+ deficiency in 1,4 NQ-BC induced phagocytic capacity depression and mitochondrial dysfunction. Sprague-Dawley rats were exposed to 1,4 NQ-BC (0, 300, 600, 1200 μg/ week) through intratracheal instillation for 30 days. Alveolar macrophages (AMs) of rats and RAW264.7 cells served as in vitro models. It was found that 1,4 NQ-BC depressed the phagocytic capacity of RAW264.7 cells. Meanwhile it reduced adenosine triphosphate (ATP) level and mitochondrial membrane potential (ΔΨm) in both AMs and RAW264.7 cells. Liquid chromatography-mass spectrometry assay revealed that 1,4 NQ-BC promoted glycolysis while depressed oxidative phosphorylation process. Notably, the reduction of Fe2+ was detected simultaneously with the upregulation of FPN1 after 1,4 NQ-BC treatment. Supplementation of ferric ammonium citrate (FAC) elevated Fe2+ level in RAW264.7 cells. Furthermore, siRNA-mediated depression of ferroportin1 (FPN1) and transcription factor EB (TFEB) overexpression could rescue 1,4 NQ-BC-induced Fe2+ deficiency. Importantly, Fe²⁺ replenishment reversed 1,4-NQ-BC-induced ATP depletion and rehabilitated mitochondrion function, hence restored phagocytic capacity of RAW264.7 cells. In conclusion, our findings identified Fe²⁺ deficiency as a sensitive mediator of 1,4 NQ-BC-induced mitochondrial and phagocytic dysfunction in macrophages. The results suggested that the rescue of Fe2+ deficiency could restore 1,4 NQ-BC induced mitochondrial dysfunction and phagocytotic disability in macrophages.

Coronary heart disease (CHD) remains one of the leading causes of death worldwide. However, systematic evaluations of CHD management quality at the community level remain limited, thereby constraining improvements in primary medical capacity. This study aims to evaluate community-based CHD management using Donabedian’s model to optimise resource allocation, standardise clinical pathways, and improve chronic disease management. Guided by Donabedian’s model, this study assessed the quality of CHD diagnosis and management within Shanghai’s primary healthcare system across three dimensions—structure, process, and outcome—from the dual perspectives of community healthcare institutions and general practitioners (GPs). A cross-sectional survey was conducted between April and May 2024, involving 247 primary healthcare institutions selected through census sampling. Within each administrative district, 50

As a novel brominated flame retardant widely used in life, 1,2-bis(2,4,6-tribromophenoxy) ethane (BTBPE) will be released into the environment. This leads to its exposure to living organisms, so it is important to explore its toxic mechanism. The liver is a major accumulation organ of BTBPE. When the liver sustains repeated damage leading to abnormal proliferation of connective tissue, this triggers hepatic fibrosis; should this process continue to progress, it will ultimately evolve into cirrhosis. In our study, BTBPE was administered to Sprague-Dawley (SD) rats, rat macrophages (RMa-bm cells) and rat hepatic stellate cells (HSCs) (HSC-T6 cells) in vivo or in vitro, respectively. This study found that BTBPE exposure caused hepatic fibrosis. This hepatic fibrosis is caused by the crosstalk between macrophage extracellular traps (METs) and HSCs activation. Firstly, exposure to BTBPE activates the miR-3570/IRX3/NOS2 axis in macrophages, thereby inducing METs. Subsequently, METs come into contact with HSCs, inhibiting the PPAR pathway in HSCs, thereby activating HSCs and producing excessive collagen and αSMA, ultimately leading to hepatic fibrosis. It is worth noting that the DNA structure in METs contributes significantly to the HSCs activation. This study for the first time discovered that the miR-3570/IRX3/NOS2 axis is involved in regulating METs, and found a relationship between METs and HSCs activation. It also found that the PPAR pathway is one of the signaling pathways involved in METs stimulating HSCs activation. This study enriches the understanding of the mechanisms of hepatic fibrosis caused by BTBPE exposure, provides new directions for the study of fibrosis, and identifies important therapeutic targets and pathways for adverse outcomes in environmental harmful factors-induced hepatic fibrosis.

Objective To evaluate the effectiveness, patient experience, and cost-efficiency of primary care versus hospital care for middle-aged and elderly patients with chronic diseases in China, in the context of achieving the triple aim of healthcare: improving population health, reducing per capita costs, and enhancing patient satisfaction.Methods A longitudinal cohort analysis using data from the China Health and Retirement Longitudinal Study (CHARLS) spanning the years 2011, 2013, 2015, and 2018.The study included participants aged 45 and older from 450 communities across mainland China, specifically targeting those with chronic diseases. Individuals without chronic conditions or with incomplete data were excluded.Results The analysis encompassed 50,800 subjects. Those who visited hospitals for outpatient treatment—mainly urban residents with higher education and income levels, and with comprehensive insurance coverage—demonstrated poorer health outcomes (OR = 1.06, 95%CI 1.02–1.10, p = 0.002) and higher medical expenses (OR = 1.99, 95% CI 1.93–2.06, p < 0.001) compared to those who utilized primary care facilities. No significant difference was observed in satisfaction levels between the two groups (OR = 0.99, 95% CI 0.92–1.07, p = 0.85).Conclusions This study indicates that for patients over 45 with chronic diseases, China's primary care can achieve health outcomes comparable to or better than large hospitals, at significantly lower costs. Despite some data limitations, it highlights the effectiveness of primary care in improving health for socioeconomically disadvantaged groups, advocating for more government investment and policy support to enhance primary care's affordability and functionality.

Background Climate change profoundly shapes the population health at the global scale. However, there was still insufficient and inconsistent evidence for the association between heat exposure and chronic kidney disease (CKD). Methods In the present study, we studied the association of heat exposure with hospitalizations for cause-specific CKD using a national inpatient database in China during the study period of hot season from 2015 to 2018. Standard time-series regression models and random-effects meta-analysis were developed to estimate the city-specific and national averaged associations at a 7 lag-day span, respectively. Results A total of 768,129 hospitalizations for CKD was recorded during the study period. The results showed that higher temperature was associated with elevated risk of hospitalizations for CKD, especially in sub-tropical cities. With a 1 °C increase in daily mean temperature, the cumulative relative risks ( RR ) over lag 0–7 d were 1.008 [95% confidence interval (CI) 1.003–1.012] for nationwide. The attributable fraction of CKD hospitalizations due to high temperatures was 5.50%. Stronger associations were observed among younger patients and those with obstructive nephropathy. Our study also found that exposure to heatwaves was associated with added risk of hospitalizations for CKD compared to non-heatwave days ( RR = 1.116, 95% CI 1.069–1.166) above the effect of daily mean temperature. Conclusions Short-term heat exposure may increase the risk of hospitalization for CKD. Our findings provide insights into the health effects of climate change and suggest the necessity of guided protection strategies against the adverse effects of high temperatures.

Introduction In China’s aging population, hypertension, aggravated by smoking, constitutes a substantial health concern. However, the effectiveness of the national public health interventions for smoking cessation under the Essential Public Health Services remains unverified. Our aim was to examine smoking prevalence, the proportion of individuals receiving smoking cessation advice, its impact on successful cessation among Chinese hypertensive patients aged ≥45 years, and to discern disparities in the coverage and efficacy of smoking cessation interventions between primary care facilities and hospitals. Methods Employing a longitudinal cohort approach, we examined four waves (2011–2018) of the China Health and Retirement Longitudinal Study (CHARLS). We surveyed a nationally representative cohort of hypertensive individuals, accounting for smoking status, cessation advice, healthcare preferences, and 11 pertinent covariates. Results Among the 4269 hypertensive patients, smokers were predominantly male, aged <65 years, with lower education and lower wealth. Smoking prevalence decreased from 25.2% in 2011 to 21.1% in 2018. The incidence of physicianprovided smoking cessation advice reached a peak of 60.3% in 2015, decreasing to 54.8% in 2018. Visitors to primary care facilities reported the highest rate of advice reception. While patients receiving advice exhibited a higher smoking prevalence, instrumental variable regression and subgroup analyses found no significant correlation between advice receipt and successful cessation. Conclusions We observed a substantial smoking prevalence among older hypertensive Chinese individuals and limited effectiveness of existing cessation programs. This underscores the necessity for augmenting primary care and devising a comprehensive health policy for more successful smoking cessation interventions, particularly considering China’s rapidly aging population.

Aim: The precise pathophysiologic pathway linking traffic-related air pollution (TRAP) to diabetes mellitus is not well elucidated. We aimed to investigate whether activation of vascular inflammation can be a mechanistic linkage between ambient TRAP and insulin resistance. Methods: Study outcomes were determined by assessing a series of circulating biomarkers indicative of insulin resistance and vascular inflammation among 73 healthy adults who underwent repeated clinical visits in Beijing, China, 2014-2016. Concomitantly, concentrations of ambient TRAP indices, including particulate matter in diameter <2.5 mu m (PM2.5), particles in size fractions of 5-560 nm, black carbon, carbon monoxide, nitrogen dioxide, and oxides of nitrogen, were continuously monitored. Results: Participants experienced extremely high levels of TRAP exposures, with mean (standard deviation) PM2.5 concentrations of 91.8 (48.3) mu g/m3, throughout the study. We found that interquartile range increases in exposure to moving average concentrations of various TRAP indices at prior up to 7 days were associated with significant elevations of 8.9-49.6% in insulin levels. Higher pollutant levels were also related to worsening metrics of insulin resistance (soluble insulin receptor ectodomain, adipokines, and homeostasis model assessment of insulin resistance) and heightened vascular inflammatory responses, particularly disruptions of the receptor activator of nuclear factor Kappa B ligand/osteoprotegerin system balance and elevations of monocyte/macrophage and T cell activation markers. Mediation analyses showed that activation of vascular inflammation could explain up to 66% of the alterations in metrics of insulin resistance attributable to air pollution. Conclusion: Our results suggest that ambient traffic pollution exposure was capable of promoting insulin resistance possibly via generating vascular inflammation.

Under the background of global warming, it has been confirmed that heat exposure has a huge impact on human health. The current study aimed to evaluate the effects of daily mean ambient temperature on hospital admissions for obstructive nephropathy (ON) at the population level. A total of 19,494 hospitalization cases for ON in Wuhan, China from January 1, 2015 to December 31, 2018 were extracted from a nationwide inpatient database in tertiary hospitals according to the International Classification of Diseases (ICD)- 10 codes. Daily ambient meteorological and pollution data during the same period were also collected. A quasi-Poisson Generalized Linear Model (GLM) combined with a distributed lag non-linear model (DLNM) was applied to analyze the lag-exposure-response relationship between daily mean temperature and daily hospital admissions for ON. Results showed that there were significantly positive associations between the daily mean temperature and ON hospital admissions. Relative to the minimum-risk temperature (-3.4 degrees C), the risk of hospital admissions for ON at moderate hot temperature (25 degrees C, 75th percentile) occurred from lag day 4 and stayed to lag day 12 (cumulative relative risk [RR] was 1.846, 95 % confidence interval [CI]: 1.135-3.005, over lag 0-12 days). Moreover, the risk of extreme hot temperature (32 degrees C, 99th percentile) appeared immediately and lasted for 8 days (RR = 2.019, 95 % CI: 1.308-3.118, over lag 0-8 days). Subgroup analyses indicated that the middle-aged and elderly (>= 45 years) patients might be more susceptible to the negative effects of high temperature, especially at moderate hot conditions. Our findings suggest that temperature may have a significant impact on the acute progression and onset of ON. Higher temperature is associated with increased risks of hospital admissions for ON, which indicates that early interventions should be taken in geographical settings with relatively high temperatures, particularly for the middle-aged and elderly.

Background:Accumulated researches revealed that both fine particulate matter (PM2.5) and sunlight exposure may be a risk factor for obesity, while researches regarding the potential effect modification by sunlight exposure on the relationship between PM2.5 and obesity are limited. We aim to investigate whether the effect of PM2.5 on obesity is affected by sunlight exposure among the general population in China.Methods:A sample of 47,204 adults in China was included. Obesity and abdominal obesity were assessed based on body mass index, waist circumference and waist-to-hip ratio, respectively. The five-year exposure to PM2.5 and sunlight were accessed using the multi-source satellite products and a geochemical transport model. The relationship between PM2.5, sunshine duration, and the obesity or abdominal obesity risk was evaluated using the general additive model.Results:The proportion of obesity and abdominal obesity was 12.6% and 26.8%, respectively. Levels of long-term PM2.5 ranged from 13.2 to 72.1 μg/m3 with the mean of 46.6 μg/m3. Each 10 μg/m3 rise in PM2.5 was related to a higher obesity risk [OR 1.12 (95% CI 1.09-1.14)] and abdominal obesity [OR 1.10 (95% CI 1.07-1.13)]. The association between PM2.5 and obesity varied according to sunshine duration, with the highest ORs of 1.56 (95% CI 1.28-1.91) for obesity and 1.66 (95% CI 1.34-2.07) for abdominal obesity in the bottom quartile of sunlight exposure (3.21-5.34 hours/day).Conclusion:Long-term PM2.5 effect on obesity risk among the general Chinese population are influenced by sunlight exposure. More attention might be paid to reduce the adverse impacts of exposure to air pollution under short sunshine duration conditions.

The cardiometabolic effects of air pollution in the context of mixtures and the underlying mechanisms remain not fully understood. This study aims to investigate the joint effect of air pollutant mixtures on a broad range of cardiometabolic parameters, examine the susceptibility of obese individuals, and determine the role of circulating fatty acids. In this panel study, metabolically healthy normal-weight (MH-NW, n = 49) and obese (MHO, n = 39) adults completed three longitudinal visits (257 person-visits in total). Personal exposure levels of PM2.5, PM10, O3, NO2, SO2, CO and BC were estimated based on fixed-site monitoring data, time-activity logs and infiltration factor method. Blood pressure, glycemic homeostasis, lipid profiles, systematic inflammation and coagulation biomarkers were measured. Targeted metabolomics was used to quantify twenty-eight plasma free fatty acids (FFAs). Bayesian kernel machine regression models were applied to establish the exposure-response relationships and identify key pollutants. Significant joint effects of measured air pollutants on systematic inflammation and coagulation biomarkers were observed in the MHO group, instead of the MH-NW group. Lipid profiles showed the most significant changes in both groups and O3 contributed the most to the total effect. Specific FFA patterns were identified, and de novo lipogenesis (DNL)-related pattern was most closely related to blood lipid profiles. In particular, interaction analysis suggested that DNL-related FFA pattern augmented the effects of O3 on triglyceride (TG, Pinteraction = 0.040), high-density lipoprotein cholesterol (HDL-C, Pinteraction = 0.106) and TG/HDL-C (Pinteraction = 0.020) in the MHO group but not MH-NW group. This modification was further confirmed by interaction analysis with estimated activity of SCD1, a key enzyme in the DNL pathway. Therefore, despite being metabolically healthy, obese subjects have a higher cardiometabolic susceptibility to air pollution, especially O3, and the DNL pathway may represent an intrinsic driver of lipid susceptibility. This study provides new insights into the cardiometabolic susceptibility of obese individuals to air pollution.

The molecular mechanisms of air pollution-associated adverse cardiovascular effects remain largely unknown. In the present study, we investigated the impacts of ambient air pollution on vascular function and the potential mediation effects of amino acids in a longitudinal follow-up of 73 healthy adults living in Beijing, China, between 2014 and 2016. We estimated associations between air pollutants and serum soluble intercellular adhesion molecule 1 (sICAM-1) and plasma levels of amino acids using linear mixed-effects models, and elucidated the biological pathways involved using mediation analyses. Higher air pollutant levels were significantly associated with increases in sICAM-1 levels. Metabolomics analysis showed that altered metabolites following short-term air pollution exposure were mainly involved in amino acid metabolism. Significant reductions in levels of plasma alanine, threonine and glutamic acid of 2.1 mu M [95% confidence interval (CI): -3.8, -0.3] to 62.0 mu M (95% CI: -76.1, -47.9) were associated with interquartile range increases in moving averages of PM2.5, BC, CO and SO2 in 1-7 days prior to clinical visits. Mediation analysis also showed that amino acids can mediate up to 48% of the changes in sICAM-1 associated with increased air pollution exposure. Our results indicated that air pollution may prompt vascular dysfunction through perturbing amino acid metabolism.

Objective Metabolic disturbance of lysophosphatidylcholine (LPC) is related with dyslipidemia. Therefore, eight single-nucleotide polymorphisms (SNPs) were selected from LPC metabolic enzymes to study their associations with obesity and serum levels of lipids. Methods A total of 3305 children were recruited from four independent studies. Eight SNPs of LPC metabolic enzymes were selected and genotyped with the matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS). The multivariable linear regression model was applied to detect the associations of eight SNPs with obesity-related phenotypes and levels of lipids in each study. Meta-analyses were used to combine the results of four studies. Results Only SNP rs4420638 of APOC-1 gene was associated with serum lipids even after Bonferroni correction. The rs4420638 was positively associated with TC ( β = 0.15, P = 8.59 × 10 −9 ) and low-density-lipoprotein-cholesterol (LDL-C, β = 0.16, P = 9.98 × 10 −14 ) individually. Conclusion The study firstly revealed the association between APOC-1/ rs4420638 and levels of serum lipids in Chinese children, providing evidence for susceptible gene variants of dyslipidemia.

Epidemiological evidence on cardiometabolic health of particulate organic matter (POM) and its sources is sparse. In a panel of 73 healthy adults in Beijing, China, daily concentrations of ambient fine particulate matter-bound polycyclic aromatic hydrocarbons (PAHs) and n-alkanes were measured throughout the study period, and Positive Matrix Factorization approach was used to identity PAHs sources. Linear mixed-effect models and mediation analyses were applied to examine the associations and potential interlink pathways between POM and biomarkers indicative of hemodynamics, insulin resistance, vascular calcification and immune inflammation. We found that significant alterations in cardiometabolic measures were associated with POM exposures. In specific, interquartile range increases in PAHs concentrations at prior up to 9 days were observed in association with significant elevations of 2.6-2.9% in diastolic blood pressure, 6.6-8.1% in soluble ST2, 10.5-14.5% in insulin, 40.9-45.7% in osteoprotegerin, and 36.3-48.7% in interleukin-17A. Greater associations were generally observed for PAHs originating from traffic emissions and coal burning. Mediation analyses revealed that POM exposures may prompt the genesis of hemodynamic abnormalities, possibly via worsening insulin resistance and calcification potential. These findings suggested that cardiometabolic health benefits would be achieved by reducing PM from combustion emissions.