Associations of various healthy dietary patterns with biological age acceleration and the mediating role of gut microbiota: results from the China Multi-Ethnic Cohort study.

To investigate the associations between dietary patterns and biological aging, identify the most recommended dietary pattern for coping with biological aging and explore the potential mediating role of gut microbiota in less-developed ethnic minority regions (LEMRs). This prospective cohort study included 8288 participants aged 30-79 years from the China Multi-Ethnic Cohort study (CMEC). Anthropometric measurements and clinical biomarkers were utilized to construct biological age based on Klemera and Doubal's method (KDM-BA) and KDM-BA acceleration (KDM-AA). Dietary information was obtained through the baseline food frequency questionnaire (FFQ). Six dietary patterns were constructed: plant-based diet index (PDI), healthful plant-based diet index (hPDI), unhealthful plant-based diet index (uPDI), healthy diet score (HDS), Dietary Approaches to Stop Hypertension (DASH), and alternative Mediterranean diets (aMED). Follow-up adjusted for baseline analysis were employed to assess the associations between dietary patterns and KDM-AA. Additionally, quantile G-computation was utilized to evaluate the significant beneficial and harmful food groups. In the subsample of 764 participants with gut microbiota data obtained through 16S rRNA gene sequencing, we used causal mediation model to explore the mediating role of gut microbiota in the associations between dietary patterns and KDM-AA. The results showed that all dietary patterns were associated with KDM-AA. Transitioning from non-compliance to compliance, DASH exhibited the strongest negative association with KDM-AA [ß = -0.91, 95%CI (-1.19, -0.63)]. The component analyses revealed that tea and soybean products were the significant beneficial food groups, while salt, preserved vegetables, red and processed meats were identified as the major harmful food groups. In mediation analysis, the decreased abundance of Synergistetes phylum and Pyramidobacter genus possibly mediated the negative associations between plant-based diets and KDM-AA (5.61%-9.19%). Overall, healthy dietary patterns, especially DASH, are negatively associated with biological aging in LEMRs. The Synergistetes and Pyramidobacter may mediate the associations between plant-based diets and biological aging. Developing appropriate strategies may promote healthy aging in LEMRs.

An Adapted Neural-Fuzzy Inference System Model Using Preprocessed Balance Data to Improve the Predictive Accuracy of Warfarin Maintenance Dosing in Patients After Heart Valve Replacement.

BACKGROUND: Tailoring warfarin use poses a challenge for physicians and pharmacists due to its narrow therapeutic window and substantial inter-individual variability. This study aimed to create an adapted neural-fuzzy inference system (ANFIS) model using preprocessed balance data to improve the predictive accuracy of warfarin maintenance dosing in Chinese patients undergoing heart valve replacement (HVR). METHODS: This retrospective study enrolled patients who underwent HVR between June 1, 2012, and June 1, 2016, from 35 centers in China. The primary outcomes were the mean difference between predicted warfarin dose by ANFIS models and actual dose and the models' predictive accuracy, including the ideal predicted percentage, the mean absolute error (MAE), and the mean squared error (MSE). The eligible cases were divided into training, internal validation, and external validation groups. We explored input variables by univariate analysis of a general linear model and created two ANFIS models using imbalanced and balanced training sets. We finally compared the primary outcomes between the imbalanced and balanced ANFIS models in both internal and external validation sets. Stratified analyses were conducted across warfarin doses (low, medium, and high doses). RESULTS: A total of 15,108 patients were included and grouped as follows: 12,086 in the imbalanced training set; 2820 in the balanced training set; 1511 in the internal validation set; and 1511 in the external validation set. Eight variables were explored as predictors related to warfarin maintenance doses, and imbalanced and balanced ANFIS models with multi-fuzzy rules were developed. The results showed a low mean difference between predicted and actual doses (< 0.3 mg/d for each model) and an accurate prediction property in both the imbalanced model (ideal prediction percentage, 74.39-78.16%; MAE, 0.37 mg/daily; MSE, 0.39 mg/daily) and the balanced model (ideal prediction percentage, 73.46-75.31%; MAE, 0.42 mg/daily; MSE, 0.43 mg/daily). Compared to the imbalanced model, the balanced model had a significantly higher prediction accuracy in the low-dose (14.46% vs. 3.01%; P < 0.001) and the high-dose warfarin groups (34.71% vs. 23.14%; P = 0.047). The results from the external validation cohort confirmed this finding. CONCLUSIONS: The ANFIS model can accurately predict the warfarin maintenance dose in patients after HVR. Through data preprocessing, the balanced model contributed to improved prediction ability in the low- and high-dose warfarin groups.

High-altitude exposure decreases bone mineral density and its relationship with gut microbiota: Results from the China multi-ethnic cohort (CMEC) study.

BACKGROUND: Geographic altitude is a potent environmental factor for human microbiota and bone mineral density. However, little evidence exists in population-based studies with altitude diversity ranges across more than 3000 m. This study assessed the associations between a wide range of altitudes and bone mineral density, as well as the potential mediating role of microbiota in this relationship. METHODS: A total of 99,556 participants from the China Multi-Ethnic Cohort (CMEC) study were enrolled. The altitude of each participant was extracted from global Shuttle Radar Topography Mission (SRTM) 4 data. Bone mineral density was measured by calcaneus quantitative ultrasound index (QUI). Stool samples were collected for 16S rRNA gene sequencing (n = 1384). The metabolites of gut microbiota, seven kinds of short-chain fatty acids (SCFAs), were detected by gas chromatography-mass spectrometry (GC-MS, n = 128). After screening, 73,974 participants were selected for the "altitude-QUI" analysis and they were placed into the low-altitude (LA) and high-altitude (HA) groups. Additionally, a subgroup (n = 1384) was further selected for the "altitude-microbiota-QUI" analysis. Multivariate linear regression models and mediation analyses were conducted among participants. RESULTS: A significant negative association between high-altitude and QUI was obtained (mean difference = -0.373 standard deviation [SD], 95% confidence interval [CI]: -0.389, -0.358, n = 73,974). The same negative association was also observed in the population with microbiota data (mean difference = -0.185 SD, 95%CI: -0.360, -0.010, n = 1384), and a significant mediating effect of Catenibacteriumon on the association between altitude and QUI (proportion mediated = 25.2%, P = 0.038) was also noticed. Additionally, the acetic acid, butyric acid, and total amount of seven SCFAs of the low-altitude group were significantly higher than that of the high-altitude group (P < 0.05). CONCLUSION: High-altitude exposure may decrease bone mineral density in adults, thus increasing the risk of osteoporosis. The modulation of gut microbiota may be a potential strategy for alleviating the decrease of bone mineral density.

Identifying the most critical behavioral lifestyles associated with MAFLD: evidence from the NHANES 2017-2020.

Background & aims: Accumulating studies have demonstrated associations between single lifestyle exposures and metabolic dysfunction-associated fatty liver disease (MAFLD). However, the joint effects of lifestyle exposures remain unclear, hindering the development of targeted prevention and control strategies. We aimed to investigate the joint associations between lifestyle exposomes and MAFLD. Methods: This study included 5,002 participants from NHANES 2017-2020. Lifestyle exposomes, including sleep duration, metabolic equivalent of task (MET), Healthy Eating Index (HEI)-2015 score, alcohol consumption, and smoke exposure, were identified from questionnaire data. MAFLD was diagnosed by vibration-controlled transient elastography measurements and laboratory data. A logistic regression model and the weighted quantile sum method were used to evaluate the associations of single and joint lifestyle exposomes, respectively, with MAFLD. The population attributable fractions (PAFs) were calculated to assess the population benefits of different intervention strategies. Results: Per-quartile range increases in sleep duration (OR=0.883, 95% CI: 0.826-0.944), MET (0.916, 0.871-0.963), and HEI-2015 score (0.827, 0.756-0.904) were significantly associated with MAFLD. The joint exposure of sleep duration, MET, and HEI-2015 score was associated with MAFLD (0.772, 0.688-0.865), with the highest weight (importance) for MET (0.526). PAFs revealed greater intervention benefits for sleep and the HEI-2015 when the majority of the population (>5%) had a low MAFLD risk (weak intervention targets), whereas MET was the most efficient intervention strategy when minority populations (≤5%) had a low MAFLD risk (strong intervention targets). Conclusion: This study demonstrated significant associations between MAFLD and single and joint exposures to sleep duration, MET, and HEI-2015 and identified physical activity as the most important lifestyle factor. Further population benefit analyses may provide evidence and suggestions for population-level interventions.

The mediation role of blood lipids on the path from air pollution exposure to MAFLD: A longitudinal cohort study.

BACKGROUND & AIMS: Recent cross-sectional studies found that exposure to ambient air pollution (AP) was associated with an increased risk of metabolic dysfunction-associated fatty liver disease (MAFLD). The alternation of blood lipids may explain the association, but epidemiological evidence is lacking. We aimed to examine whether and to what extent the association between long-term exposure to AP and incident MAFLD is mediated by blood lipids and dyslipidemia in a prospective cohort. METHODS: We included 6350 participants from the China Multi-Ethnic Cohort (CMEC, baseline 2018-2019, follow-up 2020-2021). Three-year average (2016-2018) of AP (PM1, PM2.5, PM10, NO2), blood lipids (TC, LDL-C, HDL-C, TG with their combinations) and incident MAFLD for each individual were assessed chronologically. Linear and logistic regression was used to assess the associations among AP, blood lipids, and MAFLD, and the potential mediation effects of blood lipids were evaluated using causal mediation analysis. RESULTS: A total of 744 participants were newly diagnosed with MAFLD at follow-up. The odds ratios of MAFLD associated with a 10 µm increase in PM1, PM2.5, and NO2 were 1.35 (95 % CI: 1.14, 1.58), 1.34 (1.10, 1.65) and 1.28 (1.14, 1.44), respectively. Blood lipids are important mediators between AP and incident MAFLD. LDL-C (Proportion Mediated: 6.9 %), non-HDL (13.4 %), HDL-C (20.7 %), LDL/HDL (30.1 %), and dyslipidemia (6.5 %) significantly mediated the association between PM2.5 and MAFLD. For PM1, the indirect effects were similar to those for PM2.5, with a larger value for the direct effect, and the mediation proportion by blood lipids was less for NO2. CONCLUSION: Blood lipids are important mediators between AP and MAFLD, and can explain 5 %-30 % of the association between AP and incident MAFLD, particularly cholesterol-related variables, indicating that AP could lead to MAFLD through the alternation of blood lipids. These findings provided mechanical evidence of AP leading to MAFLD in epidemiological studies.

Ambient PM2.5 Components Are Associated With Bone Strength: Evidence From a China Multi-Ethnic Study.

CONTEXT: The relationship between the components of particulate matter with an aerodynamic diameter of 2.5 or less (PM2.5) and bone strength remains unclear. OBJECTIVE: Based on a large-scale epidemiologic survey, we investigated the individual and combined associations of PM2.5 and its components with bone strength. METHODS: A total of 65 906 individuals aged 30 to 79 years were derived from the China Multi-Ethnic Cohort Annual average concentrations of PM2.5 and its components were estimated using satellite remote sensing and chemical transport models. Bone strength was expressed by the calcaneus quantitative ultrasound index (QUI) measured by quantitative ultrasound. The logistic regression model and weighted quantile sum method were used to estimate the associations of single and joint exposure to PM2.5 and its components with QUI, respectively. RESULTS: Our analysis shows that per-SD increase (µg/m3) in 3-year average concentrations of PM2.5 (mean difference [MD] -7.38; 95% CI, -8.35 to -6.41), black carbon (-7.91; -8.90 to -6.92), ammonium (-8.35; -9.37 to -7.34), nitrate (-8.73; -9.80 to -7.66), organic matter (-4.70; -5.77 to -3.64), and soil particles (-5.12; -6.10 to -4.15) were negatively associated with QUI. In addition, these associations were more pronounced in men, and people older than 65 years with a history of smoking and chronic alcohol consumption. CONCLUSION: We found that long-term exposure to PM2.5 and its components may lead to reduced bone strength, suggesting that PM2.5 and its components may potentially increase the risk of osteoporosis and even fracture. Nitrate may be responsible for increasing its risk to a greater extent.

Association of long-term exposure to ambient PM2.5 and its constituents with gut microbiota: Evidence from a China cohort.

Accumulating animal experiments and epidemiological studies have found that exposure to fine particulate matter (PM2.5) is associated with altered gut microbiota (GM). However, it is unclear what kind of role the PM2.5 constituents play in the PM2.5-GM association. Therefore, this study aimed to investigate the association of long-term exposure to PM2.5 and its constituents (PMcons) with GM. This study included 1583 participants from a cohort in Southwest China. Satellite remote sensing and chemical transport modelling were used to determine the yearly average concentrations of PMcons. GM data were derived from 16 s sequencing based on stool samples. Generalized propensity score weighting regression and Bayesian Kernel Machine Regression (BKMR) were used to estimate the individual and joint association of exposure to PMcons with the Shannon index. The weighted correlation analysis was used to estimate the association of PMcons with the composition of GM. The result showed that an interquartile range increase of 3-year average black carbon (BC), ammonium, nitrate, organic matter (OM), sulfate, and soil particles (SOIL) were negatively associated with Shannon index with mean difference (95 % confidence interval) being -0.144 (-0.208, -0.080), -0.141 (-0.205, -0.078), -0.126 (-0.184, -0.068), -0.117 (-0.172, -0.062), -0.153 (-0.221, -0.085), and - 0.153 (-0.222, -0.085). BKMR indicated joint exposure to PMcons was associated with decreased Shannon index, and BC had the largest posterior inclusion probability (0.578). Weighted correlation analyses indicated PMcons were associated with decreased Bacteroidetes (r = -0.204, P < 0.001 for PM2.5) and increased Proteobacteria (r = 0.273, P < 0.001 for PM2.5). These results revealed that long-term exposure to PMcons was associated with GM. BC was the most important constituent in the association, indicating that the source of BC should be controlled to mitigate the negative effects of PM2.5 on GM.

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.

The Preventive Value of Acupoint Sensitization for Patients with Stable Angina Pectoris: A Randomized, Double-Blind, Positive-Controlled, Multicentre Trial.

BACKGROUND: Acupoint sensitization is considered an important factor in the efficacy of acupoint therapy. This study aimed to evaluate the efficacy of acupressure in the prevention of stable angina pectoris using acupoints with different pressure-pain sensitivities. METHODS: A total of 202 patients were enrolled and randomly assigned to a high-sensitivity group (HSG) (n = 109) in which patients received acupressure at the five acupoints with the highest sensitivity to pain and a low-sensitivity group (LSG) (n = 93) in which patients received acupressure at the five acupoints with the lowest sensitivity to pain. The duration of acupressure treatment was 4 weeks, and the patients were evaluated at baseline, week 4, and week 8. The primary outcome was a change in the frequency of angina attacks from baseline. The secondary outcomes included nitroglycerin consumption, the Canadian Cardiovascular Society classification, and the Seattle Angina Questionnaire score. Adverse events such as bleeding and subcutaneous haemorrhage were recorded in both groups. RESULTS: The effect of acupressure compared with baseline on the prevention of angina pectoris in HSG was better than that in LSG at week 4 (incidence rate ratio (IRR): 0.691 and 95% confidence interval (CI): [0.569, 0.839]) and week 8 (IRR: 0.692 and 95% CI: [0.569, 0.839]). No significant difference between groups was found in the frequency of nitroglycerin consumption at week 4 (odds ratio (OR) = 0.863 and 95% CI: [0.147, 5.077]) or week 8 (OR = 1.426 and 95% CI: [0.211, 9.661]). Two themes in the questionnaire showed significantly different changes from baseline between the two groups. Scores on the angina frequency (AF) subscale had changed more from the baseline in the HSG at week 8 than in the LSG (mean difference (MD) = 3.807 and 95% CI: [0.673, 6.942]). Scores on the treatment satisfaction (TS) subscale had also changed more in the HSG than in the LSG at week 4 (MD = 3.651 and 95% CI: [0.327, 7.327]) and week 8 (MD = 4.220 and 95% CI: [0.347, 7.346]). One patient in the LSG reported bruising at the acupoint. No unexpected safety problems arose. CONCLUSIONS: This study showed that acupressure at acupoints with high sensitivity to pain may effectively reduce the frequency of stable angina pectoris episodes. This trial is registered with NCT03975140.