Effects of multiple metals exposure on abnormal liver function: The mediating role of low-density lipoprotein cholesterol.

Equilibration of metal metabolism is critical for normal liver function. Most epidemiological studies have only concentrated on the influence of limited metals. However, the single and synergistic impact of multiple-metal exposures on abnormal liver function (ALF) are still unknown. A cross-sectional study involving 1493 Chinese adults residing in Shenzhen was conducted. Plasma concentrations of 13 metals, including essential metals (calcium, copper, cobalt, iron, magnesium, manganese, molybdenum, zinc, and selenium) and toxic metals (aluminum, cadmium, arsenic, and thallium) were detected by the inductively coupled plasma spectrometry (ICP-MS). ALF was ascertained as any observed abnormality from albumin, alanine transaminase, aspartate transaminase, γ-glutamyl transpeptidase, and direct bilirubin. Diverse statistical methods were used to evaluate the single and mixture effect of metals, as well as the dose-response relationships with ALF risk, respectively. Mediation analysis was conducted to evaluate the role of blood lipids in the relation of metal exposure with ALF. The average age of subjects was 59.7 years, and 56.7 % were females. Logistic regression and the least absolute shrinkage and selection operator (LASSO) penalized regression model consistently suggested that increased levels of arsenic, aluminum, manganese, and cadmium were related to elevated risk of ALF; while magnesium and zinc showed protective effects on ALF (all p-trend < 0.05). The grouped weighted quantile sum (GWQS) regression revealed that the WQS index of essential metals and toxic metals showed significantly negative or positive relationship with ALF, respectively. Aluminum, arsenic, cadmium, and manganese showed linear whilst magnesium and zinc showed non-linear dose-response relationships with ALF risk. Mediation analysis showed that LDL-c mediated 4.41 % and 14.74 % of the relationship of plasma cadmium and manganese with ALF, respectively. In summary, plasma aluminum, arsenic, manganese, cadmium, magnesium, and zinc related with ALF, and LDL-c might underlie the pathogenesis of ALF associated with cadmium and manganese exposure. This study may provide critical public health significances in liver injury prevention and scientific evidence for the establishment of environmental standard.

Independent and joint associations of estimated cardiorespiratory fitness and its dynamic changes and obesity with the risk of hypertension: A prospective cohort.

Our aim was to examine the independent and joint associations of estimated cardiorespiratory fitness (CRF) and its changes and obesity with risk of hypertension in a rural Chinese population. A prospective cohort including 9848 adults without hypertension at baseline was enrolled. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated by logistic regression models. Restricted cubic splines were used to model the dose-response relationship. During 6 years follow-up, 2,019 individuals developed hypertension. A negative association between estimated CRF and hypertension incidence was observed, with the risk being 0.87 (0.84-0.90) per MET increment. For estimated CRF change, the risks of hypertension were 1.50 (1.27-1.77) and 0.75 (0.59-0.97) for decreasers and increasers, respectively, compared to maintainers. Joint analyses showed individuals in the overweight/obesity-fourth quartile of estimated CRF had a 2.08 times higher risk of hypertension than those in the normal weight-first quartile (Pinteraction < 0.05). Those overweight/obesity-decreasers had the highest risk (OR: 2.19, 95%CI: 1.71-2.81; Pinteraction < 0.05) compared to the normal-maintainers. Similar results for abdominal obesity were also observed. Estimated CRF and its dynamic changes showed a negative association with hypertension incidence in the rural Chinese population.

Olive oil intake and cardiovascular disease, cancer, and all-cause mortality: a systematic review and dose-response meta-analysis of prospective cohort studies.

Background: Currently, the reported links between olive oil intake and cardiovascular disease (CVD), cancer morbidity and mortality, and all-cause mortality are inconsistent. The aim of this meta-analysis is to study the reported correlations of olive oil intake with CVD, coronary heart disease (CHD), stroke and cancer incidence and mortality, and all-cause mortality. Methods: PubMed, Embase, and Web of Science were searched until March 7, 2024. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were estimated by the random-effects model. Nonlinear dose-response relationships were modeled with restricted cubic splines. This study has been registered at PROSPERO (CRD42023419001). Results: Overall, 30 articles covering 2 710 351 participants were identified. Higher olive oil intake was linked with a reduced risk of CVD incidence (RR: 0.85; 95% CI: 0.77, 0.93), CHD incidence (RR: 0.85; 95% CI: 0.72, 0.99), CVD mortality (RR: 0.77; 95% CI: 0.67, 0.88), and all-cause mortality (RR: 0.85; 95% CI: 0.81, 0.89). For a 10 g d-1 increment of olive oil intake, the risk of CVD incidence, stroke incidence, CVD mortality, and all-cause mortality decreased by 7%, 5%, 8%, and 8%, respectively. No association was found between olive oil intake and cancer incidence and mortality. Nonlinear relationships between olive oil intake and CVD and all-cause mortality were observed, with a reduced risk from intakes ranging from 0 to 18 g d-1 and 0 to 22 g d-1, respectively. Conclusion: Our study found that high olive oil intake was related to a lower risk of CVD and CHD incidence and CVD mortality and all-cause mortality.

Dietary intake changes the associations between long-term exposure to fine particulate matter and the surrogate indicators of insulin resistance.

The relationship of fine particulate matter (PM2.5) exposure and insulin resistance remains inclusive. Our study aimed to investigate this association in the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR). Specifically, we examined the associations between long-term PM2.5 exposure and three surrogate indicators of insulin resistance: the triglyceride-glucose index (TyG), TyG with waist circumference (TyG-WC) and metabolic score for insulin resistance (METS-IR). Additionally, we explored potential effect modification of dietary intake and components. Generalized estimating equations were used to evaluate the associations between PM2.5 and the indicators with an unbalanced repeated measurement design. Our analysis incorporated a total of 162,060 observations from 99,329 participants. Each 10 µg/m3 increment of PM2.5 was associated with an increase of 0.22 % [95 % confidence interval (CI): 0.20 %, 0.25 %], 1.60 % (95 % CI: 1.53 %, 1.67 %), and 2.05 % (95 % CI: 1.96 %, 2.14 %) in TyG, TyG-WC, and METS-IR, respectively. These associations were attenuated among participants with a healthy diet, particularly those with sufficient intake of fruit and vegetable, fish or tea (pinteraction < 0.0028). For instance, among participants with a healthy diet, TyG increased by 0.11 % (95 % CI: 0.08 %, 0.15 %) per 10 µg/m3 PM2.5 increment, significantly lower than the association observed in those with an unhealthy diet. The findings of this study emphasize the potential of a healthy diet to mitigate these associations, highlighting the urgency for improving air quality and implementing dietary interventions among susceptible populations in China.

Dose-response associations of triglyceride to high-density lipoprotein cholesterol ratio and triglyceride-glucose index with arterial stiffness risk.

BACKGROUND: The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and triglyceride-glucose (TyG) index are novel indexes for insulin resistance (IR). We aimed to evaluate associations of TG/HDL-C and TyG with arterial stiffness risk. METHODS: We enrolled 1979 participants from the Rural Chinese Cohort Study, examining arterial stiffness by brachial-ankle pulse wave velocity (baPWV). Logistic and linear regression models were employed to calculate effect estimates. For meta-analysis, we searched relevant articles from PubMed, Embase and Web of Science up to August 26, 2023. The fixed-effects or random-effects models were used to calculate the pooled estimates. We evaluated dose-response associations using restricted cubic splines. RESULTS: For cross-sectional studies, the adjusted ORs (95%CIs) for arterial stiffness were 1.12 (1.01-1.23) and 1.78 (1.38-2.30) for per 1 unit increment in TG/HDL-C and TyG. In the meta-analysis, the pooled ORs (95% CIs) were 1.26 (1.14-1.39) and 1.57 (1.36-1.82) for per 1 unit increment of TG/HDL-C and TyG. Additionally, both TG/HDL-C and TyG were positively related to PWV, with ß of 0.09 (95% CI 0.04-0.14) and 0.57 (95% CI 0.35-0.78) m/s. We also found linear associations of TG/HDL-C and TyG with arterial stiffness risk. CONCLUSIONS: High TG/HDL-C and TyG were related to increased arterial stiffness risk, indicating TG/HDL-C and TyG may be convincing predictors of arterial stiffness.

Visit to visit transition in TXNIP gene methylation and the risk of type 2 diabetes mellitus: a nested case-control study.

Our study aimed to investigate the association between the transition of the TXNIP gene methylation level and the risk of incident type 2 diabetes mellitus (T2DM). This study included 263 incident cases of T2DM and 263 matched non-T2DM participants. According to the methylation levels of five loci (CpG1-5; chr1:145441102-145442001) on the TXNIP gene, the participants were classified into four transition groups: maintained low, low to high, high to low, and maintained high methylation levels. Compared with individuals whose methylation level of CpG2-5 at the TXNIP gene was maintained low, individuals with maintained high methylation levels showed a 61-87% reduction in T2DM risk (66% for CpG2 [OR: 0.34, 95% CI: 0.14, 0.80]; 77% for CpG3 [OR: 0.23, 95% CI: 0.07, 0.78]; 87% for CpG4 [OR: 0.13, 95% CI: 0.03, 0.56]; and 61% for CpG5 [OR: 0.39, 95% CI: 0.16, 0.92]). Maintained high methylation levels of four loci of the TXNIP gene are associated with a reduction of T2DM incident risk in the current study. Our study suggests that preserving hypermethylation levels of the TXNIP gene may hold promise as a potential preventive measure against the onset of T2DM.

Miscarriage and stillbirth in relation to risk of cardiovascular diseases: A systematic review and meta-analysis.

INTRODUCTION: The relationship between pregnancy loss and the risk of cardiovascular diseases (CVDs) remains a matter of debate. Our intention in conducting this meta-analysis was to analyze the relationship between miscarriage and stillbirth and risk of CVDs. METHODS: PubMed, Embase, and Web of Science were systematically searched up to May 30, 2023 for all relevant studies. The random-effects model was applied to estimate the pooled relative risks (RRs) and 95% confidence intervals (95% CIs). We evaluated RR estimates for the risk of CVDs with each additional miscarriage and stillbirth through generalized least squares regression. RESULTS: Twenty-three articles were incorporated into the meta-analysis. For women with a history of miscarriage, the pooled RRs for the risk of total CVDs, coronary heart disease (CHD), stroke, and total CVD deaths were 1.16 (95 % CI 1.10-1.22), 1.26 (1.12-1.41), 1.13 (1.03-1.24), and 1.20 (1.01-1.42), respectively. For women with a history of stillbirth, the pooled RRs for the risk of total CVDs, CHD, stroke, and total CVD deaths were 1.60 (1.34-1.89), 1.30 (1.12-1.50), 1.37 (1.06-1.78), and 1.95 (1.05-3.63), respectively. With each additional miscarriage, the risk increased for total CVDs (1.08, 1.04-1.13), CHD (1.08, 1.04-1.13), and stroke (1.05, 1.00-1.10). With each additional stillbirth, the risk increased for total CVDs (1.11, 1.03-1.21) and CHD (1.13, 1.07-1.19). CONCLUSION: This meta-analysis indicates that both miscarriages and stillbirths are related to a higher risk of total CVDs, CHD, stroke, and total CVD deaths. The risk of total CVDs and CHD increased with the number of miscarriages or stillbirths.

Associations of body mass index trajectory, waist circumference trajectory, or both with type 2 diabetes mellitus risk in Chinese adults: The China-PAR project.

AIMS: To identify the trajectories of body mass index (BMI) and waist circumference (WC), and assess the associations of BMI trajectory, WC trajectory, or the two combined, with type 2 diabetes mellitus (T2DM) risk in Chinese adults. MATERIALS AND METHODS: This study was based on a prospective project-the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR). A total of 54 434 participants (39.21% men) who were measured on at least two occasions were included. Three slowly increasing trajectory patterns were identified for BMI, and four for WC, by latent mixed modelling. A nine-category variable was derived by combining the WC trajectory (low, moderate, moderate-high/high) and the BMI trajectory (low, moderate, high). Logistic regression models were applied to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The risk of developing T2DM increased with elevated BMI or WC trajectory levels (all ptrend <0.001). The risks were 2.85 (2.59-3.14) for high BMI trajectory and 4.34 (3.78-4.99) for high WC trajectory versus low trajectory groups, respectively. The association was more pronounced among younger individuals (pinteraction <0.001). In the joint analysis, compared to participants with low WC and BMI trajectory, those with moderate-high/high WC combined with high BMI trajectory had the highest risk of T2DM (OR 3.96, 95% CI 3.48-4.50); even those who maintained moderate-high/high WC but low BMI trajectory showed a higher T2DM risk (OR 3.00, 95% CI 2.31-3.91). CONCLUSIONS: This study suggests that simultaneous dynamic and continuous monitoring of BMI and WC may contribute more than single measurements to predicting T2DM risk and determining preventive strategies.

Obesity and risk of depressive disorder in children and adolescents: A meta-analysis of observational studies.

PURPOSE: This meta-analysis evaluated the relationship between overweight/obesity and depressive disorders in children and adolescents. METHODS: We examined the databases of PubMed, Embase and Web of Science for pertinent observational studies released up until 20 February 2022. The pooled relative risks (RRs) and 95% confidence intervals (CIs) of obesity and overweight with depressive disorder were calculated by means of random-effects models. The Newcastle-Ottawa Quality Assessment Scale and Agency for Healthcare Research and Quality scale were adopted to evaluate the study quality. RESULTS: Finally, for this meta-analysis, we evaluated 22 observational publications covering 175 135 participants (5 cohort study articles, 1 case-control study article and 16 cross-sectional study articles). A significant positive association was found between obesity and the risk of depression (RR 1.32, 95% CI 1.09-1.60, I2 = 79.90%, Pheterogeneity < 0.001) and in the association between obesity and depressive symptoms (RR 1.16, 95% CI: 1.00-1.35, I2 = 25.0%, Pheterogeneity = 0.247). On sensitivity analysis, the pooled RRs remained robust. Subgroup analysis indicated that obese children and teenagers in western countries were more prone to depression. CONCLUSION: Evidence from this meta-analysis, based on observational studies, supported the idea that obese children and adolescents are more likely to experience depression and depressive symptoms.

The role of mitochondrial DNA copy number in cardiometabolic disease: a bidirectional two-sample mendelian randomization study.

BACKGROUND: This study used a bidirectional 2-sample Mendelian randomization study to investigate the potential causal links between mtDNA copy number and cardiometabolic disease (obesity, hypertension, hyperlipidaemia, type 2 diabetes [T2DM], coronary artery disease [CAD], stroke, ischemic stroke, and heart failure). METHODS: Genetic associations with mtDNA copy number were obtained from a genome-wide association study (GWAS) summary statistics from the UK biobank (n = 395,718) and cardio-metabolic disease were from largest available GWAS summary statistics. Inverse variance weighting (IVW) was conducted, with weighted median, MR-Egger, and MR-PRESSO as sensitivity analyses. We repeated this in the opposite direction using instruments for cardio-metabolic disease. RESULTS: Genetically predicted mtDNA copy number was not associated with risk of obesity (P = 0.148), hypertension (P = 0.515), dyslipidemia (P = 0.684), T2DM (P = 0.631), CAD (P = 0.199), stroke (P = 0.314), ischemic stroke (P = 0.633), and heart failure (P = 0.708). Regarding the reverse directions, we only found that genetically predicted dyslipidemia was associated with decreased levels of mtDNA copy number in the IVW analysis (ß= - 0.060, 95% CI - 0.044 to - 0.076; P = 2.416e-14) and there was suggestive of evidence for a potential causal association between CAD and mtDNA copy number (ß= - 0.021, 95% CI - 0.003 to - 0.039; P = 0.025). Sensitivity and replication analyses showed the stable findings. CONCLUSIONS: Findings of this Mendelian randomization study did not support a causal effect of mtDNA copy number in the development of cardiometabolic disease, but found dyslipidemia and CAD can lead to reduced mtDNA copy number. These findings have implications for mtDNA copy number as a biomarker of dyslipidemia and CAD in clinical practice.

Somatic and Germline Variants and Coronary Heart Disease in a Chinese Population.

Importance: The genetic basis of coronary heart disease (CHD) has expanded from a germline to somatic genome, including clonal hematopoiesis of indeterminate potential (CHIP). How CHIP confers CHD risk in East Asian individuals, especially those with small clones (variant allele fraction [VAF] 0.5%-2%) and different genetic backgrounds, was completely unknown. Objective: To investigate the CHIP profile in a general Chinese cohort by deep sequencing and further explore the association between CHIP and incident CHD considering germline predisposition. Design, Setting, and Participants: This cohort study used data from 3 prospective cohorts in the project Prediction for Atherosclerotic Cardiovascular Disease Risk in China. Participants without cardiovascular disease or cancer at baseline were enrolled in 2001 and 2008 and had a median follow-up of 12.17 years extending into 2021. Exposures: CHIP mutations were detected by targeted sequencing (mean depth, 916×). A predefined CHD polygenic risk score (PRS) comprising 531 variants was used to evaluate germline predisposition. Main Outcomes and Measures: The main outcome was first incident CHD. Results: Among 6181 participants, the median (IQR) age was 53.83 years (45.35-62.39 years); 3082 participants (49.9%) were female, and 3099 (50.1%) were male. A total of 1100 individuals (17.80%) harbored 1372 CHIP mutations at baseline. CHIP was independently associated with incident CHD (hazard ratio [HR], 1.42; 95% CI, 1.18-1.72; P = 2.82 × 10-4) and presented a risk gradient with increasing VAF (P = 3.98 × 10-3 for trend). Notably, individuals with small clones, nearly half of CHIP carriers, also demonstrated a higher CHD risk compared with non-CHIP carriers (HR, 1.33; 95% CI, 1.02-1.74; P = .03) and were 4 years younger than those with VAF of 2% or greater (median age, 58.52 vs 62.70 years). Heightened CHD risk was not observed among CHIP carriers with low PRS (HR, 1.02; 95% CI, 0.64-1.64; P = .92), while high PRS and CHIP jointly contributed a 2.23-fold increase in risk (95% CI, 1.51-3.29; P = 6.29 × 10-5) compared with non-CHIP carriers with low PRS. Interestingly, the diversity in CHIP-related CHD risk within each PRS group was substantially diminished when removing variants in the inflammatory pathway from the PRS. Conclusions: This study revealed that elevated CHD risk attributed to CHIP was nonnegligible even for small clones. Inflammation genes involved in CHD could aggravate or abrogate CHIP-related CHD risk.

Fine Particulate Matter Exposure, Genetic Susceptibility, and the Risk of Incident Stroke: A Prospective Cohort Study.

BACKGROUND: Both genetic factors and environmental air pollution contribute to the risk of stroke. However, it is unknown whether the association between air pollution and stroke risk is influenced by the genetic susceptibilities of stroke and its risk factors. METHODS: This prospective cohort study included 40 827 Chinese adults without stroke history. Satellite-based monthly fine particulate matter (PM2.5) estimation at 1-km resolution was used for exposure assessment. Based on 534 identified genetic variants from genome-wide association studies in East Asians, we constructed 6 polygenic risk scores for stroke and its risk factors, including atrial fibrillation, blood pressure, type 2 diabetes, body mass index, and triglyceride. The Cox proportional hazards model was applied to evaluate the hazard ratios and 95% CIs for the associations of PM2.5 and polygenic risk score with incident stroke and the potential effect modifications. RESULTS: Over a median follow-up of 12.06 years, 3147 incident stroke cases were documented. Compared with the lowest quartile of PM2.5 exposure, the hazard ratio (95% CI) for stroke in the highest quartile group was 2.72 (2.42-3.06). Among individuals at high genetic risk, the relative risk of stroke was 57% (1.57; 1.40-1.76) higher than those at low genetic risk. Although no statistically significant interaction was found, participants with both the highest PM2.5 and high genetic risk showed the highest risk of stroke, with ≈4× that of the lowest PM2.5 and low genetic risk group (hazard ratio, 3.55 [95% CI, 2.84-4.44]). Similar upward gradients were observed in the risk of stroke when assessing the joint effects of PM2.5 and genetic risks of blood pressure, type 2 diabetes, body mass index, atrial fibrillation, and triglyceride. CONCLUSIONS: Long-term exposure to PM2.5 was associated with a higher risk of incident stroke across different genetic susceptibilities. Our findings highlighted the great importance of comprehensive assessment of air pollution and genetic risk in the prevention of stroke.

Genetic Predisposition, Sedentary Behavior, and Incident Coronary Artery Disease: A Prospective Chinese Cohort Study.

PURPOSE: Whether the association of sedentary behaviors with coronary artery disease (CAD) can be influenced by genetic susceptibility remains unclear. We aimed to investigate the joint and interplay effects between genetic risk and sedentary time (ST) and to further explore the extent to which the risk for CAD can be counteracted by reducing ST in different genetic groups. METHODS: This prospective cohort study included 39,164 Chinese adults without CAD history. Genetic susceptibility was quantified by a predefined polygenic risk score (PRS) with 540 genetic variants, and daily ST was assessed by questionnaire. We analyzed the modification effect of genetic risk on the association of ST with CAD using the Cox proportional hazards models. RESULTS: During a median follow-up of 11.60 yr, 1156 CAD events were documented. Higher ST and PRS were separately related to elevated CAD risk. Significant additive interaction was also observed (relative excess risk due to interaction: 0.77; 95% confidence interval [CI] = 0.27-1.28). Compared with participants with low genetic risk and low ST (<6 h·d -1 ), those with high genetic risk and high ST (≥10 h·d -1 ) had the highest CAD risk, with the hazard ratio (HR) and 95% CI of 4.22 (2.65-6.71). When stratified by genetic risks, participants with high ST had gradient increment of CAD risks across low, intermediate, and high genetic risk groups, with HR (95% CI) values of 1.21 (0.61-2.40), 1.57 (1.14-2.16), and 2.15 (1.40-3.31), respectively. For the absolute risk reduction, individuals with high genetic risk achieved the greatest benefit from low ST ( Ptrend = 0.024). CONCLUSIONS: Genetic susceptibility may synergistically interact with ST to increase CAD risk. Reducing ST could attenuate the CAD risk, especially among individuals with high genetic risk.

Association of methylation risk score with incident type 2 diabetes mellitus: A nested case-control study.

AIMS: To investigate the association of methylation risk score (MRS) and its interactions with environmental factors with type 2 diabetes mellitus (T2DM) risk. METHODS: We conducted a nested case-control study with 241 onset cases and 241 matched controls. Conditional logistic regression models were employed to identify risk CpG sites. Simple and weighted MRSs were constructed based on the methylation levels of ATP-binding cassette G1 gene, fat mass and obesity associated gene, potassium voltage-gated channel member 1 gene, and thioredoxin-interacting protein gene previously associated with T2DM to estimate the association of MRS with T2DM risk. Stratified analyses were used to investigate interactions between MRS and environmental factors. RESULTS: A total of 10 CpG loci were identified from the aforementioned genes to calculate MRS. After controlling for potential confounding factors, taking tertile 1 as reference, the odds ratios (ORs) and 95% confidence intervals (CIs) for T2DM of tertile 3 was 2.39 (1.36-4.20) for simple MRS and 2.59 (1.45-4.63) for weighted MRS. With per SD score increment in MRS, the OR (95% CI) was 1.66 (1.29-2.14) and 1.60 (1.24-2.08) for simple and weighted MRSs, respectively. J-curved associations were observed between both simple and weighted MRSs and T2DM risks. Additionally, multiplication interactions for smoking and hypertension with simple MRS on the risk of T2DM were found, similarly for smoking and obesity with weighted MRS on the risk of T2DM (all Pinteraction < .05). CONCLUSION: Elevated simple and weighted MRSs were associated with increased risk of T2DM. Environmental risk factors may influence the association between MRS and T2DM.

Maternal body mass index and cerebral palsy in children: A systematic review and dose-response meta-analysis.

BACKGROUND: Accumulating studies indicate that maternal obesity is associated with the risk of cerebral palsy (CP); however, their conclusions have been inconsistent. OBJECTIVES: To quantitatively estimate the association between maternal body mass index (BMI) and CP in offspring. DATA SOURCES: PubMed, Embase and Web of Science. STUDY SELECTION AND DATA EXTRACTION: Articles published up to 18 September 2022 were searched that reported the correlation between maternal BMI and CP in children. Two reviewers independently extracted data and critically assessed articles. SYNTHESIS: Pooled relative risks (RR) and 95% confidence intervals (CI) were estimated by the random-effects model. Subgroup analysis and meta-regression were performed to explore sources of heterogeneity. RESULTS: In total, 11 articles (8,407,668 participants) were identified for inclusion in our meta-analysis. For maternal underweight, no significant association was found with CP risk (RR 1.11, 95% CI 0.90, 1.38). The risk of CP was increased by 25% (RR 1.25, 95% CI 1.06, 1.47), 38% (RR 1.38, 95% CI 1.18, 1.61) and 127% (RR 2.27, 95% CI 1.82, 2.83) for maternal overweight, obesity and obesity grade 3, respectively. In addition, we observed a positive linear dose-response relationship, with the pooled risk of cerebral palsy in offspring increasing by 3% with each unit increase in maternal BMI. CONCLUSION: This meta-analysis indicates that the risk of CP in offspring grew with maternal overweight or obesity grades increasing, and was positively correlated with maternal BMI.

Lifestyle improvement and the reduced risk of cardiovascular disease: the China-PAR project.

BACKGROUND: The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease (CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project (Prediction for Atherosclerotic Cardiovascular Disease Risk in China). METHODS: A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors (LFs) (smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The risk advancement periods (RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage (PAR%) were also calculated. RESULTS: A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1 healthy LFs, maintaining 3-4 healthy LFs was associated with a 40% risk reduction of incident CVD (HR = 0.60, 95% CI: 0.45-0.79) and delayed CVD risk by 6.31 years (RAP: -6.31 [-9.92, -2.70] years). The PAR% of maintaining 3-4 unhealthy LFs was 22.0% compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2 to 3-4 was associated with a 23% lower risk of CVD (HR = 0.77, 95% CI: 0.60-0.98). CONCLUSIONS: Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.

Fruit and vegetable intake and the risk of arterial hypertension in China: A prospective cohort study.

Background: Population-based epidemiological evidence regarding the association between fruit and vegetable intake and the incidence of hypertension is inconsistent. This prospective cohort study aimed to investigate the association between fruit and vegetable intake and the risk of new-onset hypertension. Methods: Based on the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR), 58,981 Chinese adults without hypertension at baseline were included. Information on fruit and vegetable intake was collected using a food-frequency questionnaire. Cox proportional hazards models were performed to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident hypertension. Results: During 640,795 person-years of follow-up, 21,008 new cases of hypertension were recorded. Compared with participants in the lowest quintile (Q1) of total fruit and vegetable (TFV) intake, the HRs (95% CIs) of incident hypertension were 0.90 (0.86-0.95), 0.85 (0.81-0.90), 0.82 (0.78-0.86), and 0.83 (0.78-0.88) for the Q2 to Q5 group (p trend < 0.001), respectively. In further analyses categorizing participants according to the recommended intake level (500 g/day), we found that increasing the intake of TFV, even though it was still insufficient for the recommendation, also had a protective effect against the incident hypertension. When considering the intake of fruit or vegetable separately, we found similar trends as the TFV intake. Conclusion: These results suggest that a higher intake of fruit and vegetable is beneficial for preventing hypertension in Chinese adults.

Antitumor effect of tubeimoside-I on murine colorectal cancers through PKM2-dependent pyroptosis and immunomodulation.

Induction of cancer cell death is an established treatment strategy, but chemotherapy drug-mediated apoptosis can be evaded by many tumors. Pyroptosis is a type of inflammatory programmed cell death (PCD) that is important for organism immunity. Tubeimoside-I (TBMS1) is a plant-derived component that exhibits antitumor activity. However, it is unclear how TBMS1 induces pyroptosis to inhibit colorectal cancer (CRC). In this study, we demonstrated that TBMS1 is able to induce pyroptosis in murine CRC cells and releases pro-inflammatory cytokines. Mechanistically, we found that TBMS1 inhibits CRC cell proliferation and migration and induces pyroptosis by activating caspase-3 and cleaving gasdermin E (GSDME) through the inhibition of PKM2. In the animal experiments, TBMS1 attenuated the weight of solid tumors, increased the proportion of CD8+ cytotoxic T cells, and reduced the content of M2-type macrophages in the spleen of tumor-bearing mice. Furthermore, TBMS1 inhibited M2-type polarization by blocking STAT6 pathway activation in RAW 264.7 cells. To sum up, our findings suggest that TBMS1 triggers pyroptosis in CRC by acting on the PKM2/caspase-3/GSDME signaling pathway. Additionally, it modulates the antitumor immune response in CRC murine models. This study provides a promising basis for the potential use of TBMS1 in treating CRC.

Increasing trends of overweight and obesity in treatment-naive people living with HIV in Shenzhen from 2014 to 2020: an emerging health concern.

Background: With the early initiation of antiretroviral therapy (ART) in China, the demographics of treatment-naïve people living with HIV (PLWH) are moving closer to those of the general population, which is characterized by a gradual increase in metabolic indicators. However, the epidemic trends of overweight and obesity over the past decade in treatment-naïve PLWH ready to initiate ART have not yet been investigated. Methods: A cross-sectional study was conducted, including 12,135 consecutive treatment-naïve PLWH ready to initiate ART in Shenzhen, using data retrieved from the China National Free Antiretroviral Treatment Program database from 2014 to 2020. The chi-square test was used to examine the trends of overweight and obesity between age groups, and multivariate logistic regression was used to identify the association of overweight and obesity with hyperglycemia and dyslipidemia. Results: During the 7-year study period, 12,135 treatment-naïve PLWH ready to initiate ART were included, among whom 1,837 (15.1%) were overweight and 388 (3.2%) were obese. The prevalence of overweight rose from 11.4 to 17.3% (Z = -4.58, P for trend <0.01) and that of obesity from 2.0% to 4.2% (Z = -6.45, P for trend <0.01) from 2014 to 2020. The annual prevalence of overweight was the highest in the age group of participants >35 years compared to prevalence in other age groups during the period 2014-2020. Compared with those who were not overweight or obese, PLWH who were overweight or obese were more likely to have hyperglycemia (aOR 1.84, 95% CI: 1.37-2.49 for overweight; aOR 2.68, 95% CI: 1.62-4.44 for obesity), higher ALT level (aOR 2.70, 95% CI: 2.33-3.13 for overweight; aOR 3.85, 95% CI: 2.93-5.05 for obesity), higher TG levels (aOR 1.89, 95% CI 1.63-2.19 for overweight; aOR 2.56, 95% CI 1.97-3.32 for obesity), and lower HDL levels (aOR 1.67, 95% CI 1.44-1.95 for overweight; aOR 2.06, 95% CI 1.54-2.77 for obesity). Conclusion: The prevalence of overweight and obesity in treatment-naive PLWH increased steadily from 2014 to 2020 in Shenzhen. Overweight and obese in treatment-naive PLWH ready to initiate ART were associated with dyslipidemia and hyperglycemia. Public health authorities should take proactive steps to address these issues by implementing targeted screening, intervention programs including lifestyle modifications, and integrated healthcare services.

Syringaresinol alleviates IgG immune complex induced acute lung injury via activating PPARγ and suppressing pyroptosis.

Acute lung injury (ALI) is a life-threatening condition characterized by severe lung inflammation and tissue damage. In this study, we investigate the potential therapeutic efficacy of (+)-Syringaresinol (SYG), a natural compound known for its antioxidant and anti-inflammatory properties, in alleviating ALI induced by IgG immune complexes (IgG-IC). Using MH-S cells as a model, we explore SYG's ability to target peroxisome proliferator-activated receptor gamma (PPARγ) and its anti-inflammatory properties. Our comprehensive investigation aims to elucidate the specific molecular mechanisms underlying SYG's effects against pyroptosis, as revealed through transcriptomic analysis. Validation in C57BL/6 mice provides in vivo support. Our findings indicate that SYG effectively mitigates IgG-IC-induced lung damage, as evidenced by a significant reduction in lung inflammation and tissue injury. SYG treatment notably decreases pro-inflammatory cytokine levels (TNF-α, IL-6, IL-1ß) in both lung tissue and cells. Molecular docking analysis reveals SYG's robust binding to PPARγ, leading to the inhibition of IgG-IC-induced inflammatory signaling pathways. Additionally, transcriptomic analysis unveils SYG's potential in suppressing macrophage pyroptosis, potentially through the downregulation of key inflammatory mediators (NLRP3, GSDMD, Caspase-1). In summary, our study presents compelling evidence supporting SYG as an effective therapeutic agent for ALI. SYG's activation of PPARγ contributes to the suppression of NF-κB and C/EBPs expression, thereby mitigating inflammation. Moreover, SYG demonstrates the ability to inhibit macrophage pyroptosis by targeting the NLRP3/GSDMD/caspase-1 axis.