Non-linear association between long-term air pollution exposure and risk of metabolic dysfunction-associated steatotic liver disease

BACKGROUND@#Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD) has become a global epidemic, and air pollution has been identified as a potential risk factor. This study aims to investigate the non-linear relationship between ambient air pollution and MASLD prevalence.@*METHOD@#In this cross-sectional study, participants undergoing health checkups were assessed for three-year average air pollution exposure. MASLD diagnosis required hepatic steatosis with at least 1 out of 5 cardiometabolic criteria. A stepwise approach combining data visualization and regression modeling was used to determine the most appropriate link function between each of the six air pollutants and MASLD. A covariate-adjusted six-pollutant model was constructed accordingly.@*RESULTS@#A total of 131,592 participants were included, with 40.6% met the criteria of MASLD. "Threshold link function," "interaction link function," and "restricted cubic spline (RCS) link functions" best-fitted associations between MASLD and PM2.5, PM10/CO, and O3 /SO2/NO2, respectively. In the six-pollutant model, significant positive associations were observed when pollutant concentrations were over: 34.64 µg/m3 for PM2.5, 57.93 µg/m3 for PM10, 56 µg/m3 for O3, below 643.6 µg/m3 for CO, and within 33 and 48 µg/m3 for NO2. The six-pollutant model using these best-fitted link functions demonstrated superior model fitting compared to exposure-categorized model or linear link function model assuming proportionality of odds.@*CONCLUSION@#Non-linear associations were found between air pollutants and MASLD prevalence. PM2.5, PM10, O3, CO, and NO2 exhibited positive associations with MASLD in specific concentration ranges, highlighting the need to consider non-linear relationships in assessing the impact of air pollution on MASLD.

Correlation between the changing trajectories of serum uric acid and new onset nonalcoholic fatty liver disease / 中华健康管理学杂志

Objective:To explore the correlation between changing trajectories of serum uric acid and the onset of nonalcoholic fatty liver disease (NAFLD).Methods:A longitudinal cohort study. Total of 3 353 subjects who had routine health examination every year from January 2017 to December 2019 in the Health Management Center of the Second Affiliated Hospital of Dalian Medical University and met the inclusion criteria were selected as the research subjects. Four different serum uric acid trajectory groups were determined by using the group-based trajectory model: the low stability group, medium stability group, medium-high stability group and high stability group. During the follow-up to December 2021, the differences in cumulative incidence of NAFLD in different serum uric acid trajectory groups were calculated and compared. Cox proportional hazard regression model was used to evaluate the hazard ratio ( HR) and 95% confidence interval ( CI) of the NAFLD onset in different serum uric acid trajectory groups. The dose-response relationship between baseline serum uric acid and NAFLD was evaluated by a restricted cubic spline regression model. Results:The cumulative incidence of NAFLD in two years was 10.77%, and the cumulative incidence increased with the rising trajectory of serum uric acid, it was the highestin the high stability group ( P<0.05). Compared that in the low stability group, the risk of NAFLD in the other three groups was as follows: 2.24 (95% CI: 1.59-3.14) in the medium stability group, 2.89 (95% CI: 1.92-4.33) in the medium-high stability group and 4.55 (95% CI:2.83-7.31) in the high stability group (all P<0.05). The risk of NAFLD gradually increased with the rising of serum uric acid level, and the cut-off value of serum uric acid for women and men was 260.32 μmol/L and 365.09 μmol/L, respectively. Conclusions:Long-term moderate and high levels of serum uric acid are independent risk factors for the occurrence of NAFLD. With the rising of serum uric acid trajectory, the risk of NAFLD increases. Attention should be paid to the longitudinal change trend of serum uric acid level in the prevention of NAFLD, and it should be controlled within lower level of the normal range.

Interaction between hyperuricemia and gender on dyslipidemia in the elderly / 中华健康管理学杂志

Objective:To explore the interaction between hyperuricemia and gender on dyslipidemia in the elderly.Methods:A cross-sectional study. The permanent residents aged≥65 years in Kunshan City were selected by the cluster sampling method. The selected residents underwent physical examination and blood biochemical tests such as blood glucose, blood lipid, uric acid, hyaluronic acid, gamma glutamyltransferase and creatinine, and history of schistosomiasis infection was investigated. Multivariate logistic regression analysis was used to analyze the relationship between various factors and dyslipidemia. Synergy index (S), relative excess risk of interaction (RERI) and the attributable proportion due to interaction (AP) were used to evaluate the association between hyperuricemia and female interaction on dyslipidemia.. The dose-response relationship between serum uric acid level and dyslipidemia was analyzed by a restricted cubic spline regression model.Results:The prevalence of dyslipidemia in the elderly aged 65 years and obove was 31.9% (1 450/4 536), and it was 23.7% (517/2 180) and 39.6% (933/2 356) in men and women, respectively ( χ2=131.38, P<0.001). Multivariate regression showed that female, high waist circumference, overweight and obesity, hypertension, diabetes, low glomerular filtration rate, high gamma-glutamyltranspeptidase, high uric acid to creatinine ratio, low neutral to lymphocyte ratio were associated with dyslipidemia (all P<0.05). Additionally, additive interaction association was found between the dyslipidemia and advanced uric acid levels ( OR=1.09, 95% CI: 1.07-1.12) and female ( OR=1.12, 95% CI: 1.11-1.14), and the contribution rate of interaction effects was 19.8% (RERI=0.74, 95% CI: 0.06-1.42; AP=0.20, 95% CI: 0.04-0.36, S=1.37, 95% CI: 1.02-1.84). Non-linear dose response relationship was identified by the restricted cubic spline regression model between the continuously rising serum uric acid and dyslipidemia ( χ2=101.23, P<0.001). Conclusions:The proportion of dyslipidemia in elderly permanent residents is high. Demographics and physical measurement indicators comprehensively affected the prevalence of dyslipidemia. In addition, both hyperuric acid and female have additive interaction on dyslipidemia.

Analysis of risk factors of multidrug-resistant organism infection in lung transplant recipients based on restricted cubic spline model / 器官移植

Objective To summarize current status of multidrug-resistant organism (MDRO) infection in lung transplant recipients and analyze the risk factors of MDRO infection. Methods Clinical data of 321 lung transplant recipients were retrospectively analyzed. According to the incidence of postoperative MDRO infection, they were divided into the MDRO group (n=122) and non-MDRO infection group (n=199). The incidence of MDRO infection in lung transplant recipients was summarized. The risk factors of MDRO infection in lung transplant recipients were analyzed by logistic regression model. The dose-response relationship between MDRO infection and time of ventilator use was determined by restricted cubic spline model. Results Among 321 lung transplant recipients, 122 cases developed MDRO infection, with an infection rate of 38.0%. Two hundred and twenty-nine strains of pathogenic bacteria were detected in the MDRO infection group, mainly Gram-negative bacteria (92.6%), and the top three strains were carbapenem-resistant acinetobacter baumannii (46.3%), carbapenem-resistant pseudomonas aeruginosa (22.3%) and carbapenem-resistant klebsiella pneumoniae (14.8%), respectively. MDRO infection mainly consisted of lower respiratory tract infection (61.5%), followed by ventilator-associated pneumonia (26.2%). Univariate analysis showed that the risk factors of MDRO infection in lung transplant recipients were single-lung transplantation, long-time postoperative use of extracorporeal membrane oxygenation (ECMO), long operation time, long-time urinary catheterization, long-time central venous catheterization and long-time ventilator use (all P < 0.05). Multivariate logistic regression analysis indicated that single-lung transplantation and long-time ventilator use were the independent risk factors for MDRO infection in lung transplant recipients (both P < 0.05). Results of restricted cubic spline model analysis showed that the risk of infection continued to increase with the prolongation of ventilator use time within 20 d. After 20 d, prolonging the time of ventilator use failed to increase the risk of infection, showing a plateau effect. Conclusions The MDRO infection rate tends to decline in lung transplant recipients year by year. Single-lung transplantation and long-time ventilator use are the independent risk factors for MDRO infection in lung transplant recipients.

Comparison of prediction ability of two extended Cox models in nonlinear survival data analysis / 南方医科大学学报

OBJECTIVE@#To compare the predictive ability of two extended Cox models in nonlinear survival data analysis.@*METHODS@#Through Monte Carlo simulation and empirical study and with the conventional Cox Proportional Hazards model and Random Survival Forests as the reference models, we compared restricted cubic spline Cox model (Cox_RCS) and DeepSurv neural network Cox model (Cox_DNN) for their prediction ability in nonlinear survival data analysis. Concordance index was used to evaluate the differentiation of the prediction results (a larger concordance index indicates a better prediction ability of the model). Integrated Brier Score was used to evaluate the calibration degree of the prediction (a smaller index indicates a better prediction ability).@*RESULTS@#For data that met requirement of the proportion risk, the Cox_RCS model had the best prediction ability regardless of the sample size or deletion rate. For data that failed to meet the proportion risk, the prediction ability of Cox_DNN was optimal for a large sample size (≥500) with a low deletion (< 40%); the prediction ability of Cox_RCS was superior to those of other models in all other scenarios. For example data, the Cox_RCS model showed the best performance.@*CONCLUSION@#In analysis of nonlinear low maintenance data, Cox_RCS and Cox_DNN have their respective advantages and disadvantages in prediction. The conventional survival analysis methods are not inferior to machine learning or deep learning methods under certain conditions.

Association between fatty acid consumption and hypertension among rural residents in Hanzhong of Shaanxi Province / 西安交通大学学报(医学版)

【Objective】 To evaluate the associations of total fat and fatty acid consumption with the risk of hypertension among rural residents in Hanzhong, Shaanxi Province. 【Methods】 A cross-sectional survey on dietary status with a semi-quantitative food frequency questionnaire was conducted among rural residents aged between 18 and 80 years old in Hanzhong of Shaanxi. Multivariate log-binomial regression models and restricted cubic spline were used to explore the associations of dietary total fat, saturated fatty acid, polyunsaturated fatty acid and monounsaturated fatty acids with hypertension and as well as association between dose and response. 【Results】 A total of 2241 individuals were included, with 774 males and 1467 females. Monounsaturated fatty acid accounted for 51.9% of total dietary fat intake, while the other two fatty acids for 48.1%. The intake of dietary fat and any fatty acid in men was significantly in men higher than in women (P<0.001). Results of multivariable log-binomial regression indicated that after adjustment of energy, socio-demographic and lifestyles, the risk of hypertension reduced significantly in Q4 group, compared with that in Q1 (PR: 0.71, 95% CI: 0.54-0.92; P-trend: 0.022) in females. A nonlinear dose-response relationship between monounsaturated fatty acids and hypertension was detected by restricted cubic spline in women (Pnon-linear<0.01). No association was observed of total fat, saturated fatty acid and polyunsaturated fatty acid with hypertension regardless of the gender. 【Conclusion】 In women, increased consumption of monounsaturated fats might play a positive role in reducing the risk of hypertension. Further research is warranted to verify the rationality of causal inference and break-point.

Association between sedentary behavior and mortality in patients with type 2 diabetes: A dose-response relationship analysis / 中华内分泌代谢杂志

Objective To estimate the dose-response relationship between sedentary behavior with mortality in patients with type 2 diabetes. Methods A total of 17786 type 2 diabetic patients were recruited as participants, who were included in National Basic Public Health Service in Changshu County of Suzhou City, Qinghe District and Huai'an District in Huai'an City of Jiangsu Province. Cox proportional hazards regression model and restricted cubic spline model were employed to estimate the dose-response relationship between sedentary behavior with all-cause and cause specific mortality in patients with type 2 diabetes. Results Among 78114.34 person-years of the fo1low-up, the median of follow-up time was 4 years, and 1285 deaths occurred during that period. Compared to patients with sedentary behavior≤2 h/d, the multivariate adjusted hazard ratios of all-cause death associated with sedentary behavior levels of 3-4 h/d, 5-6 h/d, and≥7 h/d were 1.05(95％CI 0.92-1.20), 1.20(95％CI 1.03-1.42), and 1.39 (95％CI 1.16-1.65), respectively. Eevry increase of 1 h/d in sedentary behavior was associated with an increased hazard of death from cardiovascular disease(CVD) of 4％(HR=1.04, 95％CI 1.01-1.07) and from other causes of 6％( HR=1.06, 95％CI 1.03-1.09) . However, no significant association between sedentary behavior and malignant tumor death was found. The multivariable restrictive cubic spline regression indicated that the linear dose-response relationships were found between sedentary time with the all-cause, CVD cause, and other cause of mortality ( Non-linear test, P>0.05) . Conclusion Longer sedentary behavior could increase the risk of mortality in patients with type 2 diabetes.

Dose-response relationship between light at night and nonalcoholic fatty liver in steel workers / 中华疾病控制杂志

Objective To explore the relationship between light at night (LAN) and nonalcoholic fatty liver (NAFLD) in steel workers. Methods Relevant information was collected through questionnaires, physical examinations and blood biochemical analysis. Using restricted cubic spline (RCS) and mutiple Logistic regression model to explore the relationship between LAN and NAFLD based on a cross-sectional study. Results The prevalence of NAFLD was 33.8% (2 594 / 7 664) in steel workers. After adjusting for age, sex, marriage, educational level, smoking, drinking, body mass index, luminous intensity in life, liver enzyme metabolism, blood lipid level, physical activity, diet, sleep duration, shift work, high temperature, noise, dust, and carbon monoxide exposure, the RCS model showed a nonlinear dose-response relationship between LAN and NAFLD ( 2=71.59, P<0.001 for overall association test and 2=16.92, P<0.001 for nonlinear test); Multivariate Logistic regression model showed that after adjusting for all confounding factors, when the LAN in the 1 178 d ~ 2 017 d and 2 017 d ~ group, the prevalence of NAFLD increased by 21.7% (OR=1.217, 95% CI: 1.027-1.441) and 47.9% (OR=1.479, 95% CI: 1.240-1.763), respectively, when compared with the group LAN<1 178 d. Conclusion There is a nonlinear dose-response relationship between LAN and NAFLD in steel works.

Dose-response meta-analysis: application and practice using the R software / 한국역학회지

The objective of this study was to describe the general approaches of dose-response meta-analysis (DRMA) available for the quantitative synthesis of data using the R software. We conducted a DRMA using two types of data, the difference of means in continuous data and the odds ratio in binary data. The package commands of the R software were “doseresmeta” for the overall effect sizes that were separated into a linear model, quadratic model, and restricted cubic split model for better understanding. The effect sizes according to the dose and a test for linearity were demonstrated and interpreted by analyzing one-stage and two-stage DRMA. The authors examined several flexible models of exposure to pool study-specific trends and made a graphical presentation of the dose-response trend. This study focused on practical methods of DRMA rather than theoretical concepts for researchers who did not major in statistics. The authors hope that this study will help many researchers use the R software to perform DRMAs more easily, and that related research will be pursued.

Dose-response relationship between maternal hemoglobin concentration and preterm birth, in pregnant women / 中华流行病学杂志

Objective@#To investigate the dose-response relationship between hemoglobin concentration and preterm birth, during pregnancy.@*Methods@#With Zhuang ethnicity, a total of 12 780 pregnant women and their infants that admitted to Wuming、Pingguo、Jingxi、Debao、Longan and Tiandong hospitals, were recruited, in Guangxi Zhuang Autonomous Region, from January 2015 to December 2017. Non-conditional logistic regression method was used to analyze the effect of anemia on preterm birth during pregnancy. Dose-response relationship between hemoglobin concentration and preterm birth was explored, using the restrictive cubic spline model.@*Results@#After excluding 2 053 pregnant women with hypertension or aged 35 years and over, results from the non-conditional logistic regression analysis showed that the risk of preterm birth in the anemia group was 1.29 times (OR=1.29, 95%CI: 1.04-1.59, P=0.019) of the non-anemia group in the first trimester. Data from the restricted cubic sample showed that there appeared nonlinear "L" dose-response relationship between hemoglobin concentration and preterm birth in the first trimester and "U" shape in the third trimester (non-linearity test P<0.001).@*Conclusion@#There appeared nonlinear dose-response relationship between the hemoglobin concentration and preterm birth, both in the first and third trimesters.

Dose-response meta-analysis: application and practice using the R software / 한국역학회지

The objective of this study was to describe the general approaches of dose-response meta-analysis (DRMA) available for the quantitative synthesis of data using the R software. We conducted a DRMA using two types of data, the difference of means in continuous data and the odds ratio in binary data. The package commands of the R software were “doseresmeta” for the overall effect sizes that were separated into a linear model, quadratic model, and restricted cubic split model for better understanding. The effect sizes according to the dose and a test for linearity were demonstrated and interpreted by analyzing one-stage and two-stage DRMA. The authors examined several flexible models of exposure to pool study-specific trends and made a graphical presentation of the dose-response trend. This study focused on practical methods of DRMA rather than theoretical concepts for researchers who did not major in statistics. The authors hope that this study will help many researchers use the R software to perform DRMAs more easily, and that related research will be pursued.

Dose-Response Relationship between Alanine Aminotransferase Levels within the Reference Interval and Metabolic Syndrome in Chinese Adults

PURPOSE: Elevation in serum alanine aminotransferase (ALT) levels is a biomarker for metabolic syndrome (MS); however, the relationship has not been fully investigated within the reference interval of ALT levels. Our objective was to explore the relationship between serum ALT levels within the reference interval and MS in Chinese adults. MATERIALS AND METHODS: This cross-sectional study included 16028 adults, who attended routine health check-ups at Shengli Oilfield Central Hospital from January 2006 to March 2012. The reference interval of serum ALT level was defined as less than 40 U/L. Logistic regression models and restricted cubic spline were used to evaluate the association of ALT with MS. RESULTS: The prevalence of MS in the total population was 13.7% (6.4% for females and 18.4% for males). Multiple logistic regression showed that ALT levels were positively associated with MS after adjustment for potential confounding factors. The odds ratio of MS in the top quartile was 4.830 [95% confidence interval (CI): 2.980–7.829] in females and 3.168 (95% CI: 2.649–3.790) in males, compared with the ALT levels in the bottom quartile. The restricted cubic spline models revealed a positive non-linear dose-response relationship between ALT levels and the risk of MS in women (p for nonlinearity was 0.0327), but a positive linear dose-response relationship in men (p for nonlinearity was 0.0659). CONCLUSION: Serum ALT levels within the reference interval are positively associated with MS in a dose-response manner. Elevated ALT levels, even within the reference interval, may reflect early dysmetabolic changes.

A dose-response analysis on the association of gestational weight gain rate and the normal term neonate birth weight / 中华流行病学杂志

Objective To examine the dose-response relationship between gestational weight gain rate and the neonate birth weight.Methods A total of 18 868 women with singleton gestations who delivered between January 2006 and December 2013 were included in this study.Maternal and neonate details of these women were drawn from the Perinatal Monitoring System database.Gestational weight gain rate was defined as the total weight gain during the last and first prenatal care visits divided by the interval weeks.Both Multiple logistic regression analysis and restricted cubic spline methods were performed.Confounding factors included maternal age,education,pre-pregnancy body mass index (BMI),state of residence,parity,gestational weeks of prenatal care entry,and sex of the neonate.Results The adjusted odds ratio for macrosomia was associated with gestational weight gain rate in lower pre-pregnancy BMI (OR=3.15,95％CI:1.40-7.07),normal (OR=3.64,95％CI:2.84-4.66) or overweight (OR=2.37,95％CI:1.71-3.27).The odds ratios of low birth weight appeared a decrease in those women with lower pre-pregnancy BMI (OR=0.28,95％CI:0.13-0.61) while the normal weight (OR=0.37,95％CI:0.22-0.64) group with gestational weight gain,the rate showed an increase.Association of gestational weight gain rate for macrosomia was found a S-curve in those term delivery women (non-linearity test P＜0.000 1).However,L-curve was observed for low birth weight and gestational weight gain rate in term births (non-linearity test P＜0.000 1).Conclusion A S-curve was seen between gestational weight gain rate and term delivered macrosomia while L-curve was observed among term delivered low birth weight neonates.