Mendelian randomization(MR)is widely used in causal mediation analysis to control unmeasured confounding effects,which is valid under some strong assumptions.It is thus of great interest to assess the impact of violat...Mendelian randomization(MR)is widely used in causal mediation analysis to control unmeasured confounding effects,which is valid under some strong assumptions.It is thus of great interest to assess the impact of violations of these MR assumptions through sensitivity analysis.Sensitivity analyses have been conducted for simple MR-based causal average effect analyses,but they are not available for MR-based mediation analysis studies,and we aim to fill this gap in this paper.We propose to use two sensitivity parameters to quantify the effect due to the deviation of the IV assumptions.With these two sensitivity parameters,we derive consistent indirect causal effect estimators and establish their asymptotic propersties.Our theoretical results can be used in MR-based mediation analysis to study the impact of violations of MR as-sumptions.The finite sample performance of the proposed method is illustrated through simulation studies,sensitivity ana-lysis,and application to a real genome-wide association study.展开更多
Background Limited evidence has investigated the effect of a healthy lifestyle on mortality in patients with inflammatory bowel disease(IBD).We aimed to assess the relationship between a healthy lifestyle and all-caus...Background Limited evidence has investigated the effect of a healthy lifestyle on mortality in patients with inflammatory bowel disease(IBD).We aimed to assess the relationship between a healthy lifestyle and all-cause mortality in IBD,as well as the underlying metabolic mechanisms in a prospective cohort.Methods Overall,5052 IBD patients free of cancer(aged 57.0±8.0 years,48.5%men)were included from UK Biobank cohort.A healthy lifestyle was defined as a normal body mass index,never smoking,moderate alcohol consumption,regular physical activity,adequate sleep duration and healthy diet.The primary outcome was all-cause mortality.Lifestyle-related metabolic signatures were constructed by linear regression and elastic net regression in patients with metabolomics data.A multivariable Cox proportional hazards model was used to assess associations between lifestyle,metabolic signature and all-cause mortality.The mediation effect of lifestyle-related metabolic signatures was estimated through the Cox marginal structural model.Results During a median of 14.6 years’follow-up,583 deaths were identified.Compared with unfavourable lifestyle,those with favourable lifestyle showed significantly lower risk of all-cause mortality in IBD(HR=0.56,95%CI 0.46 to 0.68),ulcerative colitis(UC)(HR=0.61,95%CI 0.48 to 0.79)and Crohn’s disease(HR=0.49,95%CI 0.36 to 0.67),and 18.9%of the reduced risk was mediated by metabolic signature.Metabolic signature was significantly associated with lower all-cause mortality,with HR of 0.65(95%CI 0.49 to 0.85)for values above versus below the median and 0.73(95%CI 0.64 to 0.83)for per SD increase.Subgroup and sensitivity analyses demonstrated similar results.Conclusion A healthy lifestyle is associated with lower mortality in IBD patients.This beneficial effect may be mediated by metabolic signatures and related to favourable metabolic alterations.展开更多
AIM:To explore the causal relationship between several possible behavioral factors and high myopia(HM)using multivariable Mendelian randomization(MVMR)approach and to find the mediators among them with mediation analy...AIM:To explore the causal relationship between several possible behavioral factors and high myopia(HM)using multivariable Mendelian randomization(MVMR)approach and to find the mediators among them with mediation analysis.METHODS:The causal effects of several behavioral factors,including screen time,education time,time spent outdoors,and physical activity,on the risk of HM using univariable Mendelian randomization(MR)and MVMR analyses were first assessed.Genome-wide association study summary statistics of serum metabolites were also used in mediation analysis to determine the extent to which serum metabolites mediate the effects of behavioral factors on HM.RESULTS:MR analyses indicated that both increased time spent outdoors and a higher frequency of moderate physical activity significantly reduced the risk of HM.Further MVMR analysis confirmed that moderate physical activity independently contributed to a lower risk of HM.Additionally,MR analyses identified 13 serum metabolites significantly associated with HM,of which 12 were lipids and one was an amino acid derivative.Mediation analysis revealed that six lipid metabolites mediated the protective effects of moderate physical activity on HM,with the highest mediation proportion observed for 1-(1-enyl-palmitoyl)-GPC(p-16:0;30.83%).CONCLUSION:This study suggests that in addition to outdoor time,moderate physical activity habits may have an independent protective effect against HM and pointed to lipid metabolites as priority targets for the prevention due to low physical activity.These results emphasize the importance of physical activity and metabolic health in HM and underscore the need for further study of these complex associations.展开更多
Urolithiasis,a disease characterized by the formation of urinary stones,is influenced by immune system dysregulation and metabolic factors.This study investigated the interplay between specific immune cell characteris...Urolithiasis,a disease characterized by the formation of urinary stones,is influenced by immune system dysregulation and metabolic factors.This study investigated the interplay between specific immune cell characteristics and blood metabolites in urolithiasis based on Mendelian randomization.We further explored the potential mediating effects of genetically predicted blood metabolites based on mediation analysis.We employed a two-sample Mendelian randomization analysis to examine the association between immune cell properties,blood metabolites,and urolithiasis risk.Genetic instruments for immune cell characteristics and blood metabolites were used to assess causal relationships and mediating pathways.Our results indicate that 10 immune cell characteristics had a unidirectional causal association with urolithiasis risk.We also detected 13 blood metabolites associated with urolithiasis.We identified 4 pathways through which genetically predicted blood metabolites partly mediated the association between specific immune cell characteristics and urolithiasis risk.This suggests potential mechanistic links where altered blood metabolites may play a role in developing urolithiasis through immune system modulation.This Mendelian randomization study highlights the complex relationship between immune responses,blood metabolites,and urolithiasis.The findings underscore the importance of considering both immune cell features and metabolic factors in understanding the pathogenesis of urolithiasis,offering insights into novel therapeutic targets and diagnostic strategies for this disorder.展开更多
Background Epidemiological studies examining the direct and indirect effects of gestational diabetes mellitus(GDM)on offspring early childhood developmental vulnerability are lacking.Therefore,the aims of this study w...Background Epidemiological studies examining the direct and indirect effects of gestational diabetes mellitus(GDM)on offspring early childhood developmental vulnerability are lacking.Therefore,the aims of this study were to estimate the direct and indirect effects of GDM(through preterm birth)on early childhood developmental vulnerability.Methods We conducted a retrospective population-based cohort study on the association between gestational diabetes mellitus and early childhood developmental vulnerability in children born in Western Australia(WA)using maternal,infant and birth records from the Midwives Notification,Hospitalizations,Developmental Anomalies,and the Australian Early Development Census(AEDC)databases.We used two aggregated outcome measures:developmentally vulnerable on at least one AEDC domain(DV1)and developmentally vulnerable on at least two AEDC domains(DV2).Causal mediation analysis was applied to estimate the natural direct(NDE),indirect(NIE),and total(TE)effects as relative risks(RR).Results In the whole cohort(n=64,356),approximately 22%were classified as DV1 and 11%as DV2 on AEDC domains.Estimates of the natural direct effect suggested that children exposed to GDM were more likely to be classified as DV1(RR=1.20,95%CI:1.10-1.31)and DV2(RR=1.34,95%CI:1.19-1.50)after adjusting for potential confounders.About 6%and 4%of the effect of GDM on early childhood developmental vulnerability was mediated by preterm birth for DV1 and DV2,respectively.Conclusion Children exposed to gestational diabetes mellitus were more likely to be developmentally vulnerable in one or more AEDC domains.The biological mechanism for these associations is not well explained by mediation through preterm birth.展开更多
While a healthy lifestyle is known to reduce the risk of stroke,the extent to which blood pressure(BP)mediates this association remains unclear.The present study aimed to quantify the mediating role of BP in the assoc...While a healthy lifestyle is known to reduce the risk of stroke,the extent to which blood pressure(BP)mediates this association remains unclear.The present study aimed to quantify the mediating role of BP in the association between combined lifestyle factors and stroke incidence.Using data from 51929 participants free of major cardiovascular diseases or cancer at baseline,we employed structural equation modeling to assess the mediating effects of systolic(SBP)and diastolic(DBP)blood pressure.During the follow-up,2811 incident stroke cases were identified.A healthy lifestyle was significantly associated with a reduced risk of stroke,with SBP mediating 44.70%(β=-0.0014,95%confidence interval[CI]:-0.0016 to-0.0012)and DBP mediating 37.81%(β=-0.0012,95%CI:-0.0015 to-0.0009)of this association.The mediating effects were attenuated but remained significant for ischemic stroke(SBP:33.21%;DBP:27.24%).In conclusion,approximately two-fifths of the protective association between a healthy lifestyle and stroke may be mediated by BP.These findings suggest that BP control may serve as an important early indicator for evaluating the effectiveness of lifestyle interventions in reducing stroke risk.展开更多
Objective:Gut microbiota(GM)and blood metabolites are associated with the development of urticaria,yet their specific causal relationships in East Asian populations remain unclear.This study aims to elucidate the caus...Objective:Gut microbiota(GM)and blood metabolites are associated with the development of urticaria,yet their specific causal relationships in East Asian populations remain unclear.This study aims to elucidate the causal and mediating relationships among GM,blood metabolites,and urticaria in East Asians using Mendelian randomization(MR)analysis.Methods:Summary-level statistics for 500 GM taxa,112 blood metabolites,and urticaria were obtained from publicly available Genome-Wide Association Studies(GWAS)datasets.Bidirectional MR analyses were performed to examine causal associations among the GM,blood metabolites,and urticaria.The inverse variance weighted(IVW)method served as the primary analytical approach,supplemented by MR-Egger,weighted median,simple mode,and weighted mode methods.Sensitivity analyses included heterogeneity tests,horizontal pleiotropy assessments,and leave-one-out analyses.Mediation analysis was conducted to evaluate the potential mediating effects of blood metabolites on the causal pathways between GM and urticaria.Results:MR analyses identified 12 GM taxa exhibiting significant causal effects on urticaria susceptibility.Nine taxa,such as MF0017_galactose_degradation(OR=1.461,95%CI 1.098 to 1.944,P=0.009),were associated with increased urticaria risk.Three taxa,such as MF0001_arabinoxylan_degradation(OR=0.846,95%CI 0.737 to 0.973,P=0.019),showed protective effects with increased abundance.Additionally,6 blood metabolites demonstrated causal associations with urticaria.Notably,the risk of developing urticaria increases with rising fasting plasma glucose(FPG)levels(OR=1.971,95%CI 1.089 to 3.567,P=0.025).Mediation analysis further demonstrated that FPG partially mediated the protective effect of MF0001_arabinoxylan_degradation on urticaria,accounting for 11.30%of the total effect.Conclusion:This study has delineated specific GM taxa and blood metabolites that hold causal relevance to urticaria in East Asian populations.Notably,arabinogalactan degradation potentially mitigates urticaria risk via reducing FPG concentrations,offering genetic evidence to support therapeutic strategies targeting GM modulation and glucose regulation.展开更多
Objective:Chronic noncommunicable conditions are a major driver of poor health in low-and middle-income countries,yet the mental health pathways through which these illnesses shape perceived health remain underexamine...Objective:Chronic noncommunicable conditions are a major driver of poor health in low-and middle-income countries,yet the mental health pathways through which these illnesses shape perceived health remain underexamined.This study investigates whether recent mental well-being—measured using the World Health Organization Five-Item Well-Being Index(WHO-5)—mediates the association between chronic illness and self-rated health(SRH)among Egyptian adults aged 32–65.Methods:This study uses nationally representative data from the 2023 Egypt Labor Market Panel Survey(n=23,044)and estimates survey-weighted Ordinary Least Squares models predicting SRH(1=very good/excellent to 5=very bad).The key independent variable is chronic illness status.Mediation analysis is conducted using the Sobel–Goodman method with 1000 bootstrap replicates.All models adjust for sociodemographic covariates including age,sex,education,marital status,and regional residence.Results:Chronic illness is associated with significantly worse SRH(β=0.59,standard error[SE]=0.02,P<0.001).When mental well-being is added to the model,the chronic illness coefficient declines to 0.50(SE=0.02,P<0.001),and WHO-5 is independently associated with better SRH(β=-0.22,SE=0.01,P<0.001).The indirect effect via WHO-5 is 0.08(SE=0.01,P<0.001),indicating that 14.2%of the total association is mediated through recent psychological well-being.Conclusion:Although most of the self-rated health disadvantage linked to chronic illness flows through somatic and functional channels,mental well-being accounts for a meaningful share.Incorporating WHO-5 screening and stepped referral into chronic care could improve subjective health outcomes in Egypt.Mental health integration should be viewed as a critical component of equitable noncommunicable disease strategies.展开更多
BACKGROUND Cervical cancer survivors of childbearing age often face heightened reproductive anxiety due to the direct impact of the disease and its treatments on fertility.This anxiety may exacerbate psychological bur...BACKGROUND Cervical cancer survivors of childbearing age often face heightened reproductive anxiety due to the direct impact of the disease and its treatments on fertility.This anxiety may exacerbate psychological burdens,including depressive symptoms and fear of recurrence,significantly impacting quality of life.AIM To examine whether reproductive concerns partially mediate the relationship between depressive symptoms and fear of recurrence in cervical cancer patients of childbearing age.METHODS Utilizing a cross-sectional design with convenience sampling,208 eligible cervical cancer patients(aged 18-45 years,stable condition,and aware of diagnosis)from three tertiary hospitals completed validated questionnaires:The Reproductive Concerns After Cancer Scale,Patient Health Questionnaire-9,and Fear of Cancer Recurrence Questionnaire.Structural equation modeling was used to assess the mediating role of reproductive concerns in the relationship between depression and fear of recurrence.RESULTS Reproductive concerns demonstrated significant positive correlations with depression(r=0.477,P<0.001)and fear of recurrence(r=0.426,P<0.001).Structural equation modeling analysis revealed that reproductive concerns acted as a significant partial mediator between depression and fear of recurrence.The indirect effect via reproductive concerns was significant(β_indirect=0.152,P<0.001),accounting for 28.1% of the total effect of depression on fear of recurrence.CONCLUSION Identified path reveals fertility anxiety links depression to recurrence fear.Targeted psych interventions for repro concerns may ease both in childbearing cervical cancer survivors.展开更多
This letter critically examines a recent study by Zhang et al investigating the mediating role of overweight in the association between depression and new-onset diabetes among middle-aged and older adults.The study pr...This letter critically examines a recent study by Zhang et al investigating the mediating role of overweight in the association between depression and new-onset diabetes among middle-aged and older adults.The study provides com-pelling evidence that overweight mediates approximately 61%of this relationship,suggesting that depression may contribute to diabetes by influencing behaviors that lead to weight gain.This aligns with the understanding that depression can impact appetite regulation and physical activity.While the study employs a longitudinal design and robust statistical methods,limitations such as reliance on self-reported data and body mass index measurements warrant consideration.This analysis emphasizes the need for integrated interventions that address both mental and metabolic health for effective diabetes prevention.Future research should further explore the interplay of lifestyle factors,biological pathways,and social determinants in the development of this complex relationship.Ultimately,an integrated approach targeting both behavioral and biological components is crucial for the prevention and management of new-onset diabetes.展开更多
BACKGROUND Depression is a leading global health concern with high suicide rates and recurrence.Cognitive models suggest that mental pain and automatic thoughts are central to depression's impact.The hypothesis is...BACKGROUND Depression is a leading global health concern with high suicide rates and recurrence.Cognitive models suggest that mental pain and automatic thoughts are central to depression's impact.The hypothesis is that self-compassion will be negatively associated with mental pain,mediated by automatic thoughts.AIM To determine the mediating role of automatic thoughts in the relationship between self-compassion and mental pain in individuals with depression.METHODS This cross-sectional study included 389 inpatients with depression from Tianjin Anding Hospital.Participants completed the Self-Compassion Scale-Chinese Version(SCS-C),Automatic Thought Questionnaire(ATQ),and Orbach&Mikulincer Mental Pain Scale-Chinese Version(OMMP).Data were analyzed using Pearson correlations,multiple linear regressions,and mediation analysis.RESULTS The SCS-C total score was 68.95±14.89,ATQ was 87.02±28.91,and OMMP was 129.01±36.74.Correlation analysis showed mental pain was positively associated with automatic thoughts(r=0.802,P<0.001)and negatively with selfcompassion(r=-0.636,P<0.001).Regression analysis indicated automatic thoughts(β=0.623,P<0.001)and self-compassion(β=-0.301,P<0.001)significantly predicted mental pain.Mediation analysis confirmed automatic thoughts partially mediated the relationship between self-compassion and mental pain(ab=-0.269,95%CI:-0.363 to-0.212).CONCLUSION Self-compassion is inversely related to mental pain in depression,with automatic thoughts playing a mediating role.These findings suggest potential therapeutic targets for alleviating mental pain in depressed patients.展开更多
Anemia is still prevalent among low and middle-income countries,posing serious family and social burdens.However,scarce studies provided evidence for real-world exposure to polycyclic aromatic hydrocarbons(PAHs)and an...Anemia is still prevalent among low and middle-income countries,posing serious family and social burdens.However,scarce studies provided evidence for real-world exposure to polycyclic aromatic hydrocarbons(PAHs)and anemia among pregnant women,as well as involved biological mechanisms.So,we conducted this study including 1717 late pregnant women fromZunyi Birth Cohort and collected urine samples for PAHs metabolites detection.Logistic regression and restricted cubic spline regression were used to examine exposuredisease risks and dose-response relationships.We conducted Bayesian kernel machine regression,weighted quantile sum regression,and quantile g-computation regression to fit the joint impacts of multiple PAHs in the real-world scenario on hypocalcemia and anemia.Results showed single exposure to 2-OHNap,2-OHFlu,9-OHFlu,1-OHPhe,2-OHPhe,3-OHPhe,and 1-OHPyr(all P-trend<0.05)increased the risks of hypocalcemia and anemia.Moreover,PAHs mixture was significantly related to higher risks of hypocalcemia and anemia,with 3-OHPhe and 1-OHPyr identified as their major drivers,respectively.Importantly,hypocalcemia served as a significant biological mechanism responsible for PAHs and anemia.Our findings suggest that individual and joint exposure to PAHs during late pregnancy elevate the anemia risk,and calcium supplementation might be a low-cost intervention target for reducing the PAHs-related impairment on anemia for pregnant women.展开更多
Objective To identify whether metabolic status mediates the associations between frailty and mortality and incident cardiovascular disease(CVD),and to assess of interactive or joint relationships between frailty and m...Objective To identify whether metabolic status mediates the associations between frailty and mortality and incident cardiovascular disease(CVD),and to assess of interactive or joint relationships between frailty and metabolic status on these outcomes.Methods In this prospective cohort study of 456,445 UK Biobank participants,frailty was assessed using five phenotype criteria.Metabolic status was scored(0–4)based on central obesity,hypertension,hyperglycemia,and dyslipidemia.Multivariable-adjusted Cox regression models were used to assess the associations between frailty and mortality and incident CVD.Results During a median follow-up of 13.8 years for mortality and 13.6 years for CVD,30,907 deaths(7,467 CVD-related)and 37,115 incident CVD cases occurred.Frailty was associated with higher risks of all-cause mortality(hazard ratio[HR],2.41;95%confidence interval[CI],2.31–2.51),CVD mortality(HR,2.64;95%CI,2.43–2.87),and incident CVD(HR,1.83;95%CI,1.75–1.91),compared with non-frail individuals.Metabolic status mediated 8.7%,16.1%,and 16.4%of these associations,respectively.Frailty and metabolic status interacted multiplicatively for all-cause mortality(P-value for interaction<0.001)and additively for CVD mortality[relative excess risk due to interaction(RERI),1.78;95%CI,0.88–2.68]and incident CVD(RERI,0.60;95%CI,0.33–0.86).Joint exposure to frailty and three to four metabolic disorders conferred 3.34-,6.32-,and 3.30-fold risks of all-cause mortality,CVD mortality,and incident CVD,respectively,compared with metabolically healthy non-frail individuals.Conclusion This study highlights the need for integrated management strategies targeting both frailty and metabolic conditions to mitigate cardiovascular and mortality risks.展开更多
Background Coronary artery calcification(CAC),a hallmark of atherosclerosis,paradoxically associates with reduced cardiovascular risk under statin therapy despite accelerated calcification progression,prompting this s...Background Coronary artery calcification(CAC),a hallmark of atherosclerosis,paradoxically associates with reduced cardiovascular risk under statin therapy despite accelerated calcification progression,prompting this study to explore CAC metrics as potential mediators between statin use and major adverse cardiovascular events(MACE).Methods Clinical data of 246 hospitalized patients who underwent coronary computed tomography angiography(CCTA)at Guangdong Provincial People's Hospital from January 2023 to June 2023 were retrospectively analyzed.Linear regression was used to evaluate the relationship between statin use and CAC parameters.Multivariable Poisson regression models were applied to explore the associations of statin use and CAC parameters with MACE risk.A mediation analysis was performed to assess the role of CAC parameters in the statin-MACE relationship.Results Statin use was independently associated with increased calcification score(β=0.648,P<0.001),CAC volume(β=0.623,P<0.001),and calcified plaque proportion(β=0.606,P=0.002).Multivariable Poisson regression indicated that statin use significantly reduced MACE risk[incidence rate ratio(IRR):0.33,P=0.018],whereas calcification score(IRR:2.63,P=0.026)and CACvolume(IRR:2.66,P=0.044)were associated with elevated MACE risk;Calcified plaque proportion showed no significant association.Mediation analysis revealed that calcification score(β=0.035,P=0.021)and CAC volume(β=0.023,P=0.018)exerted masking effects,while calcified plaque proportion had no mediating role.Conclusions Calcification score and CACvolume demonstrated limited masking effects in the association between statin use and MACE.展开更多
The associations of volatile organic compounds(VOCs)exposure with short sleep duration(SSD)have rarely been studied.We aimed to evaluate the correlation between VOC exposure and SSD risk,while also exploring the poten...The associations of volatile organic compounds(VOCs)exposure with short sleep duration(SSD)have rarely been studied.We aimed to evaluate the correlation between VOC exposure and SSD risk,while also exploring the potential mediating influence of depressive symptoms.Blood concentrations of seven VOCs,namely benzene,toluene,ethylbenzene,m-/p-xylene,o-xylene,styrene(collectively known as BTEXS),and 1,4-dichlorobenzene,were analyzed in 2905 U.S.adults.Weighted logistic regression,quantile-based g-computation(QGC),and weighted quantile sum(WQS)regression were employed to investigate associations between selected VOCs and SSD risk.Mediation analyses were conducted to explore the potential mediating effects of depressive symptoms on these relationships.Increased blood levels of BTEXS were positively correlated with SSD risk,with odds ratios(OR)ranging from 1.130 to 1.212(all P<0.05).A nonlinear association between toluene concentration and SSD risk was observed(P for nonlinearity=0.028).Both QGC and WQS analyses indicated a positive association between co-exposure to VOCs and SSD,with styrene showing the highest positive weights(QGC:OR=1.313,95%confidence interval(CI):1.038–1.660;WQS:OR=1.386,95%CI:1.111–1.731).Furthermore,BTEXS exposure was positively linked to depressive symptoms,which in turn were significantly associated with SSD risk.Mediation analyses revealed that depressive symptoms partially mediated the relationships between individual and mixed VOCs and SSD risk,with mediation proportions ranging from 15.87%to 20.54%(all P<0.05).These findings indicated that exposure to VOCs increased SSD risk,with depressive symptoms playing a partial mediating role.展开更多
To investigate how spatial heterogeneity affects the so-called“resource curse”in China,we combine a careful selection of indicators with the concept of resource industry spatial agglomeration(RISA)as a proxy for res...To investigate how spatial heterogeneity affects the so-called“resource curse”in China,we combine a careful selection of indicators with the concept of resource industry spatial agglomeration(RISA)as a proxy for resource abundance and dependency.To address RISA heterogeneity among regions,those lacking a spatial concentration in non-resource industries are excluded from the analysis.We then develop an econometric model of regional economic growth(REG)using RISA.To further investigate the impact mechanisms of RISA and other factors influencing REG,we use the feasible generalized least squares(FGLS)method and the system generalized method of moments(SGMM).Conducting a stepwise regression analysis,we systematically examine the effect of the resource curse at the regional level from a RISA perspective.Our key findings are as follows:①Fifteen provinces in China exhibit RISA,and their level of economic development is significantly lower than that of provinces without a spatial agglomeration of resource industries.②RISA and REG exhibit a“U-shaped”relationship,characterized initially by suppression followed by promotion.③In terms of transmission mechanisms,investments in material and human capital,the degree of openness to foreign trade,and residents’savings rate all suppress RISA,while investments in technological innovation,development of the private economy and the manufacturing industry,and government intervention can promote spatial agglomeration of resource industries.展开更多
Objective To study the importance of digital economy to promote the innovation development of enterprises under the background of the era of information technology reform.Methods The maximum entropy method was used to...Objective To study the importance of digital economy to promote the innovation development of enterprises under the background of the era of information technology reform.Methods The maximum entropy method was used to measure the comprehensive level of digital economy development at provincial level.Besides,the impact of digital economy on the innovation performance of pharmaceutical industry was investigated empirically by using A-share pharmaceutical companies listed in China from 2013 to 2020 as a research sample,and the mediating mechanism of R&D investment and financing constraints on the impact was examined.Results and Conclusion It is found that digital economy is significantly and positively related to the innovation performance of enterprises.The mechanism test shows that digital economy improves innovation performance through the expansion effect of R&D investment and alleviating financing constraints.In the context that digital economy has become a new driving force for enterprise innovation,the combination of digital economy and real economy should be actively promoted,R&D investment in pharmaceutical enterprises should be increased,and financing channels should be broadened.展开更多
Motivated by an analysis of causal mechanism from economic stress to entrepreneurial withdrawals through depressed affect,we develop a two-layer generalized varying coefficient mediation model.This model captures the ...Motivated by an analysis of causal mechanism from economic stress to entrepreneurial withdrawals through depressed affect,we develop a two-layer generalized varying coefficient mediation model.This model captures the bridging effects of mediators that may vary with another variable,by treating them as smooth functions of this variable.It also allows various response types by introducing the generalized varying coefficient model in the first layer.The varying direct and indirect effects are estimated through spline expansion.The theoretical properties of the estimated direct and indirect coefficient functions including estimation biases,asymptotic distributions and so forth,are explored.Simulation studies validate the finite-sample performance of the proposed estimation method.A real data analysis based on the proposed model discovers some interesting behavioral economic phenomenon,that self-efficacy influences the deleterious impact of economic stress,both directly and indirectly through depressed affect,on business owners’withdrawal intentions.展开更多
Background This study aimed to investigate the relationship between overall obesity,central obesity and brain volumes,as well as to determine the extent to which cardiometabolic and inflammatory measures act as mediat...Background This study aimed to investigate the relationship between overall obesity,central obesity and brain volumes,as well as to determine the extent to which cardiometabolic and inflammatory measures act as mediators in the association between body mass index(BMI),waist-hip ratio(WHR)and brain volumes.Methods In the context of counterfactual framework,mediation analysis was used to explore the potential mediation in which cardiometabolic and inflammatory measures may mediate the relationship between BMI,WHR,and brain volumes.Results Among 2413 community-dwelling participants,those with high BMI or WHR levels experienced an approximately brain ageing of 4 years.Especially,individuals with high WHR or BMI under the age of 65 exhibited white matter hyperintensity volume(WMHV)differences equivalent to around 5 years of ageing.Conversely,in the high-level WHR population over the age of 65,premature brain ageing in gray matter volume(GMV)exceeded 4.5 years.For GMV,more than 45%of the observed effect of WHR was mediated by glycaemic metabolism indicators.This proportion increases to 78.70%when blood pressure,triglyceride,leucocyte count,and neutrophil count are jointly considered with glycaemic metabolism indicators.Regarding WHR and BMI’s association with WMHV,cardiometabolic and inflammatory indicators,along with high-density lipoprotein cholesterol,mediated 35.50%and 20.20%of the respective effects.Conclusions Overall obesity and central obesity were associated with lower GMV and higher WMHV,a process that is partially mediated by the presence of cardiometabolic and inflammatory measures.展开更多
基金This work was supported by the National Natural Science Foundation of China(12171451,72091212).
文摘Mendelian randomization(MR)is widely used in causal mediation analysis to control unmeasured confounding effects,which is valid under some strong assumptions.It is thus of great interest to assess the impact of violations of these MR assumptions through sensitivity analysis.Sensitivity analyses have been conducted for simple MR-based causal average effect analyses,but they are not available for MR-based mediation analysis studies,and we aim to fill this gap in this paper.We propose to use two sensitivity parameters to quantify the effect due to the deviation of the IV assumptions.With these two sensitivity parameters,we derive consistent indirect causal effect estimators and establish their asymptotic propersties.Our theoretical results can be used in MR-based mediation analysis to study the impact of violations of MR as-sumptions.The finite sample performance of the proposed method is illustrated through simulation studies,sensitivity ana-lysis,and application to a real genome-wide association study.
基金supported by the National Key Research and Development Program of China(Nos.2022YFC3602100 and 2022YFC3602104)Beijing Nova Program(No.20230484349)Beijing Hospitals Authority Innovation Studio of Young Staff(No.202303)。
文摘Background Limited evidence has investigated the effect of a healthy lifestyle on mortality in patients with inflammatory bowel disease(IBD).We aimed to assess the relationship between a healthy lifestyle and all-cause mortality in IBD,as well as the underlying metabolic mechanisms in a prospective cohort.Methods Overall,5052 IBD patients free of cancer(aged 57.0±8.0 years,48.5%men)were included from UK Biobank cohort.A healthy lifestyle was defined as a normal body mass index,never smoking,moderate alcohol consumption,regular physical activity,adequate sleep duration and healthy diet.The primary outcome was all-cause mortality.Lifestyle-related metabolic signatures were constructed by linear regression and elastic net regression in patients with metabolomics data.A multivariable Cox proportional hazards model was used to assess associations between lifestyle,metabolic signature and all-cause mortality.The mediation effect of lifestyle-related metabolic signatures was estimated through the Cox marginal structural model.Results During a median of 14.6 years’follow-up,583 deaths were identified.Compared with unfavourable lifestyle,those with favourable lifestyle showed significantly lower risk of all-cause mortality in IBD(HR=0.56,95%CI 0.46 to 0.68),ulcerative colitis(UC)(HR=0.61,95%CI 0.48 to 0.79)and Crohn’s disease(HR=0.49,95%CI 0.36 to 0.67),and 18.9%of the reduced risk was mediated by metabolic signature.Metabolic signature was significantly associated with lower all-cause mortality,with HR of 0.65(95%CI 0.49 to 0.85)for values above versus below the median and 0.73(95%CI 0.64 to 0.83)for per SD increase.Subgroup and sensitivity analyses demonstrated similar results.Conclusion A healthy lifestyle is associated with lower mortality in IBD patients.This beneficial effect may be mediated by metabolic signatures and related to favourable metabolic alterations.
基金Supported by the Central High Level Hospital Clinical Research Funding(No.BJ-2024-089).
文摘AIM:To explore the causal relationship between several possible behavioral factors and high myopia(HM)using multivariable Mendelian randomization(MVMR)approach and to find the mediators among them with mediation analysis.METHODS:The causal effects of several behavioral factors,including screen time,education time,time spent outdoors,and physical activity,on the risk of HM using univariable Mendelian randomization(MR)and MVMR analyses were first assessed.Genome-wide association study summary statistics of serum metabolites were also used in mediation analysis to determine the extent to which serum metabolites mediate the effects of behavioral factors on HM.RESULTS:MR analyses indicated that both increased time spent outdoors and a higher frequency of moderate physical activity significantly reduced the risk of HM.Further MVMR analysis confirmed that moderate physical activity independently contributed to a lower risk of HM.Additionally,MR analyses identified 13 serum metabolites significantly associated with HM,of which 12 were lipids and one was an amino acid derivative.Mediation analysis revealed that six lipid metabolites mediated the protective effects of moderate physical activity on HM,with the highest mediation proportion observed for 1-(1-enyl-palmitoyl)-GPC(p-16:0;30.83%).CONCLUSION:This study suggests that in addition to outdoor time,moderate physical activity habits may have an independent protective effect against HM and pointed to lipid metabolites as priority targets for the prevention due to low physical activity.These results emphasize the importance of physical activity and metabolic health in HM and underscore the need for further study of these complex associations.
基金support from various sources including the Innovation and Development Joint Fund of Chongqing Natural Science Foundation of China(No.CST-B2023NSCQ-LZX0099)Chongqing Science and Health Joint Medical High-end Talent Project(China)(No.2022GDRC012)+3 种基金Science and Technology Research Program of Chongqing Municipal Education Commission of China(No.KJZD-K202100402)CQMU Program for Youth Innovation in Future Medicine(Chongqing,China)(No.W0073)National Natural Science Foundation of China(82401866)Special Grants for Postdoctoral Research Projects in Chongqing in 2023(2023CQBSHTB3134).
文摘Urolithiasis,a disease characterized by the formation of urinary stones,is influenced by immune system dysregulation and metabolic factors.This study investigated the interplay between specific immune cell characteristics and blood metabolites in urolithiasis based on Mendelian randomization.We further explored the potential mediating effects of genetically predicted blood metabolites based on mediation analysis.We employed a two-sample Mendelian randomization analysis to examine the association between immune cell properties,blood metabolites,and urolithiasis risk.Genetic instruments for immune cell characteristics and blood metabolites were used to assess causal relationships and mediating pathways.Our results indicate that 10 immune cell characteristics had a unidirectional causal association with urolithiasis risk.We also detected 13 blood metabolites associated with urolithiasis.We identified 4 pathways through which genetically predicted blood metabolites partly mediated the association between specific immune cell characteristics and urolithiasis risk.This suggests potential mechanistic links where altered blood metabolites may play a role in developing urolithiasis through immune system modulation.This Mendelian randomization study highlights the complex relationship between immune responses,blood metabolites,and urolithiasis.The findings underscore the importance of considering both immune cell features and metabolic factors in understanding the pathogenesis of urolithiasis,offering insights into novel therapeutic targets and diagnostic strategies for this disorder.
基金Open Access funding enabled and organized by CAUL and its Member Institutions.GP was supported with funding from the National Health and Medical Research Council Project and Investigator Grants#1099655 and#1173991the Research Council of Norway through its Centres of Excellence funding scheme#262700GAT was supported with funding from the National Health and Medical Research Council Investigator Grant#1195716.
文摘Background Epidemiological studies examining the direct and indirect effects of gestational diabetes mellitus(GDM)on offspring early childhood developmental vulnerability are lacking.Therefore,the aims of this study were to estimate the direct and indirect effects of GDM(through preterm birth)on early childhood developmental vulnerability.Methods We conducted a retrospective population-based cohort study on the association between gestational diabetes mellitus and early childhood developmental vulnerability in children born in Western Australia(WA)using maternal,infant and birth records from the Midwives Notification,Hospitalizations,Developmental Anomalies,and the Australian Early Development Census(AEDC)databases.We used two aggregated outcome measures:developmentally vulnerable on at least one AEDC domain(DV1)and developmentally vulnerable on at least two AEDC domains(DV2).Causal mediation analysis was applied to estimate the natural direct(NDE),indirect(NIE),and total(TE)effects as relative risks(RR).Results In the whole cohort(n=64,356),approximately 22%were classified as DV1 and 11%as DV2 on AEDC domains.Estimates of the natural direct effect suggested that children exposed to GDM were more likely to be classified as DV1(RR=1.20,95%CI:1.10-1.31)and DV2(RR=1.34,95%CI:1.19-1.50)after adjusting for potential confounders.About 6%and 4%of the effect of GDM on early childhood developmental vulnerability was mediated by preterm birth for DV1 and DV2,respectively.Conclusion Children exposed to gestational diabetes mellitus were more likely to be developmentally vulnerable in one or more AEDC domains.The biological mechanism for these associations is not well explained by mediation through preterm birth.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.82192900,82192901,82192904,81390540,and 91846303 to L.L.)the National Key Research and Development Program of China(Grant No.2016YFC0900500 to Y.G.)the Kadoorie Charitable Foundation in Hong Kong,and the Wellcome Trust in the UK(Grant/Award Nos.088158/Z/09/Z,104085/Z/14/Z,and 202922/Z/16/Z to Z.C.).
文摘While a healthy lifestyle is known to reduce the risk of stroke,the extent to which blood pressure(BP)mediates this association remains unclear.The present study aimed to quantify the mediating role of BP in the association between combined lifestyle factors and stroke incidence.Using data from 51929 participants free of major cardiovascular diseases or cancer at baseline,we employed structural equation modeling to assess the mediating effects of systolic(SBP)and diastolic(DBP)blood pressure.During the follow-up,2811 incident stroke cases were identified.A healthy lifestyle was significantly associated with a reduced risk of stroke,with SBP mediating 44.70%(β=-0.0014,95%confidence interval[CI]:-0.0016 to-0.0012)and DBP mediating 37.81%(β=-0.0012,95%CI:-0.0015 to-0.0009)of this association.The mediating effects were attenuated but remained significant for ischemic stroke(SBP:33.21%;DBP:27.24%).In conclusion,approximately two-fifths of the protective association between a healthy lifestyle and stroke may be mediated by BP.These findings suggest that BP control may serve as an important early indicator for evaluating the effectiveness of lifestyle interventions in reducing stroke risk.
基金supported by the Natural Science Foundation of Hunan Province,China(2024JJ7627).
文摘Objective:Gut microbiota(GM)and blood metabolites are associated with the development of urticaria,yet their specific causal relationships in East Asian populations remain unclear.This study aims to elucidate the causal and mediating relationships among GM,blood metabolites,and urticaria in East Asians using Mendelian randomization(MR)analysis.Methods:Summary-level statistics for 500 GM taxa,112 blood metabolites,and urticaria were obtained from publicly available Genome-Wide Association Studies(GWAS)datasets.Bidirectional MR analyses were performed to examine causal associations among the GM,blood metabolites,and urticaria.The inverse variance weighted(IVW)method served as the primary analytical approach,supplemented by MR-Egger,weighted median,simple mode,and weighted mode methods.Sensitivity analyses included heterogeneity tests,horizontal pleiotropy assessments,and leave-one-out analyses.Mediation analysis was conducted to evaluate the potential mediating effects of blood metabolites on the causal pathways between GM and urticaria.Results:MR analyses identified 12 GM taxa exhibiting significant causal effects on urticaria susceptibility.Nine taxa,such as MF0017_galactose_degradation(OR=1.461,95%CI 1.098 to 1.944,P=0.009),were associated with increased urticaria risk.Three taxa,such as MF0001_arabinoxylan_degradation(OR=0.846,95%CI 0.737 to 0.973,P=0.019),showed protective effects with increased abundance.Additionally,6 blood metabolites demonstrated causal associations with urticaria.Notably,the risk of developing urticaria increases with rising fasting plasma glucose(FPG)levels(OR=1.971,95%CI 1.089 to 3.567,P=0.025).Mediation analysis further demonstrated that FPG partially mediated the protective effect of MF0001_arabinoxylan_degradation on urticaria,accounting for 11.30%of the total effect.Conclusion:This study has delineated specific GM taxa and blood metabolites that hold causal relevance to urticaria in East Asian populations.Notably,arabinogalactan degradation potentially mitigates urticaria risk via reducing FPG concentrations,offering genetic evidence to support therapeutic strategies targeting GM modulation and glucose regulation.
文摘Objective:Chronic noncommunicable conditions are a major driver of poor health in low-and middle-income countries,yet the mental health pathways through which these illnesses shape perceived health remain underexamined.This study investigates whether recent mental well-being—measured using the World Health Organization Five-Item Well-Being Index(WHO-5)—mediates the association between chronic illness and self-rated health(SRH)among Egyptian adults aged 32–65.Methods:This study uses nationally representative data from the 2023 Egypt Labor Market Panel Survey(n=23,044)and estimates survey-weighted Ordinary Least Squares models predicting SRH(1=very good/excellent to 5=very bad).The key independent variable is chronic illness status.Mediation analysis is conducted using the Sobel–Goodman method with 1000 bootstrap replicates.All models adjust for sociodemographic covariates including age,sex,education,marital status,and regional residence.Results:Chronic illness is associated with significantly worse SRH(β=0.59,standard error[SE]=0.02,P<0.001).When mental well-being is added to the model,the chronic illness coefficient declines to 0.50(SE=0.02,P<0.001),and WHO-5 is independently associated with better SRH(β=-0.22,SE=0.01,P<0.001).The indirect effect via WHO-5 is 0.08(SE=0.01,P<0.001),indicating that 14.2%of the total association is mediated through recent psychological well-being.Conclusion:Although most of the self-rated health disadvantage linked to chronic illness flows through somatic and functional channels,mental well-being accounts for a meaningful share.Incorporating WHO-5 screening and stepped referral into chronic care could improve subjective health outcomes in Egypt.Mental health integration should be viewed as a critical component of equitable noncommunicable disease strategies.
基金Supported by National Natural Science Foundation Youth Project,No.72204123China Social Welfare Foundation-Nurse Care Fund,No.HLCXKT-20230130.
文摘BACKGROUND Cervical cancer survivors of childbearing age often face heightened reproductive anxiety due to the direct impact of the disease and its treatments on fertility.This anxiety may exacerbate psychological burdens,including depressive symptoms and fear of recurrence,significantly impacting quality of life.AIM To examine whether reproductive concerns partially mediate the relationship between depressive symptoms and fear of recurrence in cervical cancer patients of childbearing age.METHODS Utilizing a cross-sectional design with convenience sampling,208 eligible cervical cancer patients(aged 18-45 years,stable condition,and aware of diagnosis)from three tertiary hospitals completed validated questionnaires:The Reproductive Concerns After Cancer Scale,Patient Health Questionnaire-9,and Fear of Cancer Recurrence Questionnaire.Structural equation modeling was used to assess the mediating role of reproductive concerns in the relationship between depression and fear of recurrence.RESULTS Reproductive concerns demonstrated significant positive correlations with depression(r=0.477,P<0.001)and fear of recurrence(r=0.426,P<0.001).Structural equation modeling analysis revealed that reproductive concerns acted as a significant partial mediator between depression and fear of recurrence.The indirect effect via reproductive concerns was significant(β_indirect=0.152,P<0.001),accounting for 28.1% of the total effect of depression on fear of recurrence.CONCLUSION Identified path reveals fertility anxiety links depression to recurrence fear.Targeted psych interventions for repro concerns may ease both in childbearing cervical cancer survivors.
基金Supported by the New Professor Research Program of KOREATECH,No.202501930001.
文摘This letter critically examines a recent study by Zhang et al investigating the mediating role of overweight in the association between depression and new-onset diabetes among middle-aged and older adults.The study provides com-pelling evidence that overweight mediates approximately 61%of this relationship,suggesting that depression may contribute to diabetes by influencing behaviors that lead to weight gain.This aligns with the understanding that depression can impact appetite regulation and physical activity.While the study employs a longitudinal design and robust statistical methods,limitations such as reliance on self-reported data and body mass index measurements warrant consideration.This analysis emphasizes the need for integrated interventions that address both mental and metabolic health for effective diabetes prevention.Future research should further explore the interplay of lifestyle factors,biological pathways,and social determinants in the development of this complex relationship.Ultimately,an integrated approach targeting both behavioral and biological components is crucial for the prevention and management of new-onset diabetes.
文摘BACKGROUND Depression is a leading global health concern with high suicide rates and recurrence.Cognitive models suggest that mental pain and automatic thoughts are central to depression's impact.The hypothesis is that self-compassion will be negatively associated with mental pain,mediated by automatic thoughts.AIM To determine the mediating role of automatic thoughts in the relationship between self-compassion and mental pain in individuals with depression.METHODS This cross-sectional study included 389 inpatients with depression from Tianjin Anding Hospital.Participants completed the Self-Compassion Scale-Chinese Version(SCS-C),Automatic Thought Questionnaire(ATQ),and Orbach&Mikulincer Mental Pain Scale-Chinese Version(OMMP).Data were analyzed using Pearson correlations,multiple linear regressions,and mediation analysis.RESULTS The SCS-C total score was 68.95±14.89,ATQ was 87.02±28.91,and OMMP was 129.01±36.74.Correlation analysis showed mental pain was positively associated with automatic thoughts(r=0.802,P<0.001)and negatively with selfcompassion(r=-0.636,P<0.001).Regression analysis indicated automatic thoughts(β=0.623,P<0.001)and self-compassion(β=-0.301,P<0.001)significantly predicted mental pain.Mediation analysis confirmed automatic thoughts partially mediated the relationship between self-compassion and mental pain(ab=-0.269,95%CI:-0.363 to-0.212).CONCLUSION Self-compassion is inversely related to mental pain in depression,with automatic thoughts playing a mediating role.These findings suggest potential therapeutic targets for alleviating mental pain in depressed patients.
基金supported by the Science&Technology Program of Guizhou Province(Nos.QKHPTRC-GCC[2022]039-1,QKHPTRC-CXTD[2022]014,and QKHHBZ[2020]3002)the Scientific Research Programof Guizhou Provincial Department of Education(No.QJJ[2023]019).
文摘Anemia is still prevalent among low and middle-income countries,posing serious family and social burdens.However,scarce studies provided evidence for real-world exposure to polycyclic aromatic hydrocarbons(PAHs)and anemia among pregnant women,as well as involved biological mechanisms.So,we conducted this study including 1717 late pregnant women fromZunyi Birth Cohort and collected urine samples for PAHs metabolites detection.Logistic regression and restricted cubic spline regression were used to examine exposuredisease risks and dose-response relationships.We conducted Bayesian kernel machine regression,weighted quantile sum regression,and quantile g-computation regression to fit the joint impacts of multiple PAHs in the real-world scenario on hypocalcemia and anemia.Results showed single exposure to 2-OHNap,2-OHFlu,9-OHFlu,1-OHPhe,2-OHPhe,3-OHPhe,and 1-OHPyr(all P-trend<0.05)increased the risks of hypocalcemia and anemia.Moreover,PAHs mixture was significantly related to higher risks of hypocalcemia and anemia,with 3-OHPhe and 1-OHPyr identified as their major drivers,respectively.Importantly,hypocalcemia served as a significant biological mechanism responsible for PAHs and anemia.Our findings suggest that individual and joint exposure to PAHs during late pregnancy elevate the anemia risk,and calcium supplementation might be a low-cost intervention target for reducing the PAHs-related impairment on anemia for pregnant women.
基金supported by grants from the National Natural Science Foundation of China(82192902 and 82325043)the National Key R&D Program of China(2023YFC3606300)supported by grants from the National Natural Science Foundation of China(82273623 and 82073554).
文摘Objective To identify whether metabolic status mediates the associations between frailty and mortality and incident cardiovascular disease(CVD),and to assess of interactive or joint relationships between frailty and metabolic status on these outcomes.Methods In this prospective cohort study of 456,445 UK Biobank participants,frailty was assessed using five phenotype criteria.Metabolic status was scored(0–4)based on central obesity,hypertension,hyperglycemia,and dyslipidemia.Multivariable-adjusted Cox regression models were used to assess the associations between frailty and mortality and incident CVD.Results During a median follow-up of 13.8 years for mortality and 13.6 years for CVD,30,907 deaths(7,467 CVD-related)and 37,115 incident CVD cases occurred.Frailty was associated with higher risks of all-cause mortality(hazard ratio[HR],2.41;95%confidence interval[CI],2.31–2.51),CVD mortality(HR,2.64;95%CI,2.43–2.87),and incident CVD(HR,1.83;95%CI,1.75–1.91),compared with non-frail individuals.Metabolic status mediated 8.7%,16.1%,and 16.4%of these associations,respectively.Frailty and metabolic status interacted multiplicatively for all-cause mortality(P-value for interaction<0.001)and additively for CVD mortality[relative excess risk due to interaction(RERI),1.78;95%CI,0.88–2.68]and incident CVD(RERI,0.60;95%CI,0.33–0.86).Joint exposure to frailty and three to four metabolic disorders conferred 3.34-,6.32-,and 3.30-fold risks of all-cause mortality,CVD mortality,and incident CVD,respectively,compared with metabolically healthy non-frail individuals.Conclusion This study highlights the need for integrated management strategies targeting both frailty and metabolic conditions to mitigate cardiovascular and mortality risks.
文摘Background Coronary artery calcification(CAC),a hallmark of atherosclerosis,paradoxically associates with reduced cardiovascular risk under statin therapy despite accelerated calcification progression,prompting this study to explore CAC metrics as potential mediators between statin use and major adverse cardiovascular events(MACE).Methods Clinical data of 246 hospitalized patients who underwent coronary computed tomography angiography(CCTA)at Guangdong Provincial People's Hospital from January 2023 to June 2023 were retrospectively analyzed.Linear regression was used to evaluate the relationship between statin use and CAC parameters.Multivariable Poisson regression models were applied to explore the associations of statin use and CAC parameters with MACE risk.A mediation analysis was performed to assess the role of CAC parameters in the statin-MACE relationship.Results Statin use was independently associated with increased calcification score(β=0.648,P<0.001),CAC volume(β=0.623,P<0.001),and calcified plaque proportion(β=0.606,P=0.002).Multivariable Poisson regression indicated that statin use significantly reduced MACE risk[incidence rate ratio(IRR):0.33,P=0.018],whereas calcification score(IRR:2.63,P=0.026)and CACvolume(IRR:2.66,P=0.044)were associated with elevated MACE risk;Calcified plaque proportion showed no significant association.Mediation analysis revealed that calcification score(β=0.035,P=0.021)and CAC volume(β=0.023,P=0.018)exerted masking effects,while calcified plaque proportion had no mediating role.Conclusions Calcification score and CACvolume demonstrated limited masking effects in the association between statin use and MACE.
文摘The associations of volatile organic compounds(VOCs)exposure with short sleep duration(SSD)have rarely been studied.We aimed to evaluate the correlation between VOC exposure and SSD risk,while also exploring the potential mediating influence of depressive symptoms.Blood concentrations of seven VOCs,namely benzene,toluene,ethylbenzene,m-/p-xylene,o-xylene,styrene(collectively known as BTEXS),and 1,4-dichlorobenzene,were analyzed in 2905 U.S.adults.Weighted logistic regression,quantile-based g-computation(QGC),and weighted quantile sum(WQS)regression were employed to investigate associations between selected VOCs and SSD risk.Mediation analyses were conducted to explore the potential mediating effects of depressive symptoms on these relationships.Increased blood levels of BTEXS were positively correlated with SSD risk,with odds ratios(OR)ranging from 1.130 to 1.212(all P<0.05).A nonlinear association between toluene concentration and SSD risk was observed(P for nonlinearity=0.028).Both QGC and WQS analyses indicated a positive association between co-exposure to VOCs and SSD,with styrene showing the highest positive weights(QGC:OR=1.313,95%confidence interval(CI):1.038–1.660;WQS:OR=1.386,95%CI:1.111–1.731).Furthermore,BTEXS exposure was positively linked to depressive symptoms,which in turn were significantly associated with SSD risk.Mediation analyses revealed that depressive symptoms partially mediated the relationships between individual and mixed VOCs and SSD risk,with mediation proportions ranging from 15.87%to 20.54%(all P<0.05).These findings indicated that exposure to VOCs increased SSD risk,with depressive symptoms playing a partial mediating role.
基金Ministry of Education Humanities and Social Sciences Research General Project“Study on the Responsibility Sharing Accounting and Accountability Mechanism for Coordinated Air Pollution Control in the Yellow River Basin”Project[Grant No.24YJC630260].
文摘To investigate how spatial heterogeneity affects the so-called“resource curse”in China,we combine a careful selection of indicators with the concept of resource industry spatial agglomeration(RISA)as a proxy for resource abundance and dependency.To address RISA heterogeneity among regions,those lacking a spatial concentration in non-resource industries are excluded from the analysis.We then develop an econometric model of regional economic growth(REG)using RISA.To further investigate the impact mechanisms of RISA and other factors influencing REG,we use the feasible generalized least squares(FGLS)method and the system generalized method of moments(SGMM).Conducting a stepwise regression analysis,we systematically examine the effect of the resource curse at the regional level from a RISA perspective.Our key findings are as follows:①Fifteen provinces in China exhibit RISA,and their level of economic development is significantly lower than that of provinces without a spatial agglomeration of resource industries.②RISA and REG exhibit a“U-shaped”relationship,characterized initially by suppression followed by promotion.③In terms of transmission mechanisms,investments in material and human capital,the degree of openness to foreign trade,and residents’savings rate all suppress RISA,while investments in technological innovation,development of the private economy and the manufacturing industry,and government intervention can promote spatial agglomeration of resource industries.
文摘Objective To study the importance of digital economy to promote the innovation development of enterprises under the background of the era of information technology reform.Methods The maximum entropy method was used to measure the comprehensive level of digital economy development at provincial level.Besides,the impact of digital economy on the innovation performance of pharmaceutical industry was investigated empirically by using A-share pharmaceutical companies listed in China from 2013 to 2020 as a research sample,and the mediating mechanism of R&D investment and financing constraints on the impact was examined.Results and Conclusion It is found that digital economy is significantly and positively related to the innovation performance of enterprises.The mechanism test shows that digital economy improves innovation performance through the expansion effect of R&D investment and alleviating financing constraints.In the context that digital economy has become a new driving force for enterprise innovation,the combination of digital economy and real economy should be actively promoted,R&D investment in pharmaceutical enterprises should be increased,and financing channels should be broadened.
基金Liu’s research was supported by NNSFC 12271456,71988101the Ministry of Education Research in the Humanities and Social Sciences 22YJA910002.
文摘Motivated by an analysis of causal mechanism from economic stress to entrepreneurial withdrawals through depressed affect,we develop a two-layer generalized varying coefficient mediation model.This model captures the bridging effects of mediators that may vary with another variable,by treating them as smooth functions of this variable.It also allows various response types by introducing the generalized varying coefficient model in the first layer.The varying direct and indirect effects are estimated through spline expansion.The theoretical properties of the estimated direct and indirect coefficient functions including estimation biases,asymptotic distributions and so forth,are explored.Simulation studies validate the finite-sample performance of the proposed estimation method.A real data analysis based on the proposed model discovers some interesting behavioral economic phenomenon,that self-efficacy influences the deleterious impact of economic stress,both directly and indirectly through depressed affect,on business owners’withdrawal intentions.
基金supported by National Key R&D Programme of China(No.2022YFC3602500,2022YFC3602505)National Natural Science Foundation of China(81971091)+3 种基金Outstanding Young Talents Project of Capital Medical University(A2105)Capital’s Funds for Health Improvement and Research(2020-1-2041)Key Science&Technologies R&D Programme of Lishui City(2019ZDYF18)Zhejiang Provincial Programme for the Cultivation of High-level Innovative Health talents and AstraZeneca Investment(China)Co.,Ltd.
文摘Background This study aimed to investigate the relationship between overall obesity,central obesity and brain volumes,as well as to determine the extent to which cardiometabolic and inflammatory measures act as mediators in the association between body mass index(BMI),waist-hip ratio(WHR)and brain volumes.Methods In the context of counterfactual framework,mediation analysis was used to explore the potential mediation in which cardiometabolic and inflammatory measures may mediate the relationship between BMI,WHR,and brain volumes.Results Among 2413 community-dwelling participants,those with high BMI or WHR levels experienced an approximately brain ageing of 4 years.Especially,individuals with high WHR or BMI under the age of 65 exhibited white matter hyperintensity volume(WMHV)differences equivalent to around 5 years of ageing.Conversely,in the high-level WHR population over the age of 65,premature brain ageing in gray matter volume(GMV)exceeded 4.5 years.For GMV,more than 45%of the observed effect of WHR was mediated by glycaemic metabolism indicators.This proportion increases to 78.70%when blood pressure,triglyceride,leucocyte count,and neutrophil count are jointly considered with glycaemic metabolism indicators.Regarding WHR and BMI’s association with WMHV,cardiometabolic and inflammatory indicators,along with high-density lipoprotein cholesterol,mediated 35.50%and 20.20%of the respective effects.Conclusions Overall obesity and central obesity were associated with lower GMV and higher WMHV,a process that is partially mediated by the presence of cardiometabolic and inflammatory measures.
