Interferon-related genes are involved in antiviral responses,inflammation,and immunity,which are closely related to sepsis-associated acute respiratory distress syndrome(ARDS).We analyzed 1972 participants with genoty...Interferon-related genes are involved in antiviral responses,inflammation,and immunity,which are closely related to sepsis-associated acute respiratory distress syndrome(ARDS).We analyzed 1972 participants with genotype data and 681 participants with gene expression data from the Molecular Epidemiology of ARDS(MEARDS),the Molecular Epidemiology of Sepsis in the ICU(MESSI),and the Molecular Diagnosis and Risk Stratification of Sepsis(MARS)cohorts in a three-step study focusing on sepsis-associated ARDS and sepsis-only controls.First,we identified and validated interferon-related genes associated with sepsis-associated ARDS risk using genetically regulated gene expression(GReX).Second,we examined the association of the confirmed gene(interferon regulatory factor 1,IRF1)with ARDS risk and survival and conducted a mediation analysis.Through discovery and validation,we found that the GReX of IRF1 was associated with ARDS risk(odds ratio[OR_(MEARDS)]=0.84,P=0.008;OR_(MESSI)=0.83,P=0.034).Furthermore,individual-level measured IRF1 expression was associated with reduced ARDS risk(OR=0.58,P=8.67×10^(-4)),and improved overall survival in ARDS patients(hazard ratio[HR_(28-day)]=0.49,P=0.009)and sepsis patients(HR_(28-day)=0.76,P=0.008).Mediation analysis revealed that IRF1 may enhance immune function by regulating the major histocompatibility complex,including HLA-F,which mediated more than 70%of protective effects of IRF1 on ARDS.The findings were validated by in vitro biological experiments including time-series infection dynamics,overexpression,knockout,and chromatin immunoprecipitation sequencing.Early prophylactic interventions to activate IRF1 in sepsis patients,thereby regulating HLA-F,may reduce the risk of ARDS and mortality,especially in severely ill patients.展开更多
Carbon black(CB)is a vital constituent of airborne pollutants,comprising diesel exhaust and fine particulate matter(PM_(2.5)),aswell as a prevalent manufacturingmaterial.CBwas known to cause pulmonary dysfunction and ...Carbon black(CB)is a vital constituent of airborne pollutants,comprising diesel exhaust and fine particulate matter(PM_(2.5)),aswell as a prevalent manufacturingmaterial.CBwas known to cause pulmonary dysfunction and fibrosis.However,the detailedmolecular mechanisms underlying fibrosis development are poorly understood.In this study,18 C57BL/6mice were randomized into two groups and exposed to CB and filtered air(FA)for 28 days,with 6 hr/day and 7 days perweek exposure regimen,respectively.The human normal bronchial epithelial cell line(BEAS-2B)was subjected to CB treatment for 24 h in vitro,with CB concentrations in 0,50,100,and 200μg/mL.Our study indicated that exposure to CB resulted in a reduction in lung function and the development of pulmonary fibrosis in mice.Furthermore,our results showed cytoskeleton rearrangement and epithelial-mesenchymal transition(EMT)phenotype in BEAS-2B cells were happened,after CB exposure.Subsequent studies revealed that elevated expression of THBS2 after CB primarily contributed to the development of pulmonary fibrosis.The research findings from both in vivo and in vitro studies provided evidence that piR-713551 was involved in CB exposure-induced EMT by targeting the THBS2 gene and activating theβ-catenin pathway.Mechanically,piR-713551/PIWIL4 complex activated the THBS2 transcription by recruitment of histone demethyltransferase KDM4A to reduce H3K9me3 modification at the THBS2 gene promoter.Conclusively,our research showed that CB exposure could activate EMT and lead pulmonary fibrosis which was modulated by piR-713551/PIWIL4 targeting THBS2.展开更多
Previous studies have suggested that abnormal hepatobiliary system function may contribute to poor prognosis in patientswith acute coronary syndrome(ACS)and that abnormal hepatobiliary system function may be associate...Previous studies have suggested that abnormal hepatobiliary system function may contribute to poor prognosis in patientswith acute coronary syndrome(ACS)and that abnormal hepatobiliary system function may be associated with per-and polyfluoroalkyl substances(PFAS)exposure.However,there is limited evidence for this association in cardiovascular subpopulations,particularly in the ACS patients.Therefore,we performed this study to evaluate the association between plasma PFAS exposure and hepatobiliary system function biomarkers in patients with ACS.This study included 546 newly diagnosed ACS patients at the Second Hospital of Hebei Medical University,and data on 15 hepatobiliary system function biomarkers were obtained from medical records.Associations between single PFAS and hepatobiliary system function biomarkers were assessed using multiple linear regression models and restricted cubic spline model(RCS),and mixture effects were assessed using the Quantile g-computation model.The results showed that total bile acids(TBA)was negative associated with perfluorohexane sulfonic acid(PFHxS)(-7.69%,95%CI:-12.15%,-3.01%).According to the RCS model,linear associations were found between TBA and PFHxS(P for overall=0.003,P for non-linear=0.234).We also have observed the association between between PFAS congeners and liver enzyme such as aspartate aminotransferase(AST)and α-l-Fucosidase(AFU),but it was not statistically significant after correction.In addition,Our results also revealed an association between prealbumin(PA)and PFAS congeners as well as mixtures.Our findings have provided a piece of epidemiological evidence on associations between PFAS congeners or mixture,and serum hepatobiliary system function biomarkers in ACS patients,which could be a basis for subsequent mechanism studies.展开更多
Although per-and polyfluoroalkyl substances(PFAS)have been frequently linked to cardiovascular and renal disease separately,evidence remains scarce regarding their systematic effect.Therefore,we recruited 546 newly di...Although per-and polyfluoroalkyl substances(PFAS)have been frequently linked to cardiovascular and renal disease separately,evidence remains scarce regarding their systematic effect.Therefore,we recruited 546 newly diagnosed acute coronary syndrome(ACS)patients and detected seven myocardial enzymes and six kidney function biomarkers.Twelve PFASwere also assessedwith ultra-high-performance liquid chromatography-tandem mass spectrometry.Generalized linear model and restricted cubic spline model were applied to single pollutant analysis.Quantile g-computation was used for mixture analysis.Network model was utilized to identify central and bridge nodes of pollutants and phenotypes.In the present study,perfluorohexane sulfonic acid was positively associated with uric acid(UA)(β=0.04,95%confidence interval(CI):0.01,0.07),and perfluorobutanoic acid was negatively associated with estimated glomerular filtration rate(β=-0.04,95%CI:-0.07,-0.01)but positively associated with UA(β=0.03,95%CI:0.01,0.06).In mixture analysis,each quantile increase in the PFAS mixture was significantly associated with UA(β=0.08,95%CI:0.04,0.11).Network analysis revealed that perfluorooctanoate,UA,and myoglobin were denoted as bridge nodes,and the first principal component of lactate dehydrogenase and creatine kinase-myocardial band was identified as the node with the highest strength and expected influence.This study investigates the systematic impact of PFAS exposure through cardiorenal interaction network,which highlights that PFAS may serve as an upstream approach in UA-modulated cardiorenal network to affect cardiorenal system comprehensively.展开更多
Emerging evidence highlights the role of thyroid hormones in cancer,although findings are controversial.Research on thyroid-related traits in lung carcinogenesis is limited.Using UK Biobank data,we performed bidirecti...Emerging evidence highlights the role of thyroid hormones in cancer,although findings are controversial.Research on thyroid-related traits in lung carcinogenesis is limited.Using UK Biobank data,we performed bidirectional Mendelian randomization(MR)to assess causal associations between lung cancer risk and thyroid dysfunction(hypothyroidism and hyperthyroidism)or functional traits(free thyroxine[FT4]and normal-range thyroid-stimulating hormone[TSH]).Furthermore,in the smoking-behavior-stratified MR analysis,we evaluated the mediating effect of thyroid-related phenotypes on the association between smoking behaviors and lung cancer.We demonstrated significant associations between lung cancer risk and hypothyroidism(hazard ratio[HR]=1.14,95%confidence interval[CI]=1.03–1.26,P=0.009)and hyperthyroidism(HR=1.55,95%CI=1.29–1.87,P=1.90×10^(-6))in the UKB.Moreover,the MR analysis indicated a causal effect of thyroid dysfunction on lung cancer risk(ORinverse variance weighted[IVW]=1.09,95%CI=1.05–1.13,P=3.12×10^(-6)for hypothyroidism;ORIVW=1.08,95%CI=1.04–1.12,P=8.14×10^(-5)for hyperthyroidism).We found that FT4 levels were protective against lung cancer risk(ORIVW=0.93,95%CI=0.87–0.99,P=0.030).Additionally,the stratified MR analysis demonstrated distinct causal effects of thyroid dysfunction on lung cancer risk among smokers.Hyperthyroidism mediated the effect of smoking behaviors,especially the age of smoking initiation(17.66%mediated),on lung cancer risk.Thus,thyroid dysfunction phenotypes play causal roles in lung cancer development exclusively among smokers and act as mediators in the causal pathway from smoking to lung cancer.展开更多
Associations of per-and polyfluoroalkyl substances(PFAS)on lipid metabolism have been documented but research remains scarce regarding effect of PFAS on lipid variability.To deeply understand their relationship,a step...Associations of per-and polyfluoroalkyl substances(PFAS)on lipid metabolism have been documented but research remains scarce regarding effect of PFAS on lipid variability.To deeply understand their relationship,a step-forward in causal inference is expected.To address these,we conducted a longitudinal study with three repeated measurements involving 201 participants in Beijing,among which 100 eligible participants were included for the present study.Twenty-three PFAS and four lipid indicators were assessed at each visit.We used linear mixed models and quantile g-computation models to investigate associations between PFAS and blood lipid levels.A latent class growth model described PFAS serum exposure patterns,and a generalized linear model demonstrated associations between these patterns and lipid variability.Our study found that PFDA was associated with increased TC(β=0.083,95%CI:0.011,0.155)and HDL-C(β=0.106,95%CI:0.034,0.178).The PFAS mixture also showed a positive relationship with TC(β=0.06,95%CI:0.02,0.10),with PFDA contributing most positively.Compared to the low trajectory group,the middle trajectory group for PFDA was associated with VIM of TC(β=0.756,95%CI:0.153,1.359).Furthermore,PFDA showed biological gradientswith lipid metabolism.This is the first repeated-measures study to identify the impact of PFAS serum exposure pattern on the lipid metabolism and the first to estimate the association between PFAS and blood lipid levels in middle-aged and elderly Chinese and reinforce the evidence of their causal relationship through epidemiological studies.展开更多
Objective:This study aimed to construct a model that predicts invasive lung cancer using longitudinal radiological features from multiple low-dose computed tomography(LDCT)scans,thereby addressing overdiagnosis in lun...Objective:This study aimed to construct a model that predicts invasive lung cancer using longitudinal radiological features from multiple low-dose computed tomography(LDCT)scans,thereby addressing overdiagnosis in lung cancer screening.Methods:In this retrospective study,628 patients with pulmonary nodules who underwent three LDCT scans followed by surgical resection were categorized into invasive carcinoma(n=155)and non-invasive nodule(n=473)groups on the basis of pathological diagnosis.This derivation aimed to identify risk factors and construct a multivariate logistic model.The predictive performance was externally validated in two independent cohorts(retrospectively designed,n=252;prospectively designed,n=269).The discrimination and calibration of the model were evaluated using area under the curve(AUC),and calibration plots.Decision curve analysis(DCA)was further performed to evaluate the net benefit in practical clinical scenarios.Results:The model,termed multiple CTs-invasive lung cancer(MCT-ILC),incorporated eleven factors encompassing nodule features at baseline and feature variability during follow-up.The standard deviation of diameter variability(SD_(diameter))was the most reliable predictor,with an odds ratio[95% confidence interval(95%CI)of 7.35(5.32-10.16)(P<0.001)].AUCs with 95% CIs for the MCT-ILC model were 0.912(0.864-0.960)and 0.906(0.833-0.979)in the two testing cohorts and were superior to those for the model containing only features at baseline(PD_(elong)=0.002 and 0.021,respectively).For calibration,the Brier scores of the MCT-ILC model were0.091(95% CI:0.064-0.118) and 0.078(95% CI:0.055-0.101)in the two test sets.The decision curve image showed that the MCT-ILC model was the only model that maintained positive net benefits across the entire threshold range.Furthermore,the MCT-ILC model score could classify more than 90% of patients with invasive nodules into the high-risk group.Conclusions:The MCT-ILC model could assess pulmonary nodule invasiveness,potentially mitigating overdiagnosis in lung cancer screening.展开更多
目的:探讨食管癌高发区——淮安市楚州区居民的食管癌危险因素。方法:采用以人群为基础的1?2匹配的病例对照研究方法,用专门设计的调查表对207例食管癌病例及414例正常对照者进行1对1的询问调查,采用条件logistic回归分析法对所获得的...目的:探讨食管癌高发区——淮安市楚州区居民的食管癌危险因素。方法:采用以人群为基础的1?2匹配的病例对照研究方法,用专门设计的调查表对207例食管癌病例及414例正常对照者进行1对1的询问调查,采用条件logistic回归分析法对所获得的调查资料进行统计学分析。结果:人均月收入低、体质指数(body mass index,BMI)偏低、既往食管病变、不按时就餐、10年前喜食辣食、10年前喜食烫食、喜食肥肉、不食大蒜和肿瘤家族史等可能是食管癌的危险因素。结论:饮食习惯、人均月收入、既往食管病变等因素可影响食管癌的发生,应针对相关危险因素采取相应的预防措施。展开更多
Objective To estimate the burden of cirrhosis and other chronic liver diseases caused by specific etiologies in China.Methods Data from the Global Burden of Disease Study 2016(GBD 2016)were used.We evaluated the burde...Objective To estimate the burden of cirrhosis and other chronic liver diseases caused by specific etiologies in China.Methods Data from the Global Burden of Disease Study 2016(GBD 2016)were used.We evaluated the burden by analyzing age-sex-province-specific prevalence,mortality,and disability-adjusted lifeyears(DALYs)of 33 provinces in China.Results From 1990 to 2016,prevalence cases in thousands increased by 73.7%from 6833.3(95%UI:6498.0–7180.6)to 11869.6(95%UI:11274.6–12504.7).Age-standardized mortality and DALY rates per100,000 decreased by 51.2%and 53.3%,respectively.Male and elderly people(aged≥60 years)preponderance were found for prevalence,mortality,and DALYs.The number of prevalence cases,deaths,and DALYs due to hepatitis C virus(HCV)increased by 86.6%,8.7%,and 0.9%,respectively.Also,age-standardized prevalence rates decreased in 31 provinces,but increased in Yunnan and Shandong.The Socio-demographic Index(SDI)values were negatively correlated with age-standardized mortality and DALY rates by provinces in 2016;the correlation coefficients were-0.817 and-0.828,respectively.Conclusion Cirrhosis and other chronic liver diseases remain a huge health burden in China,with the increase of population and the aging of population.Hepatitis B virus(HBV)remains the leading cause of the health burden in China.展开更多
Objective To investigate the association between ambient air pollution and hospital emergency admissions in Beijing. Methods In this study, a semi-parametric generalized additive model （GAM） was used to evaluate the...Objective To investigate the association between ambient air pollution and hospital emergency admissions in Beijing. Methods In this study, a semi-parametric generalized additive model （GAM） was used to evaluate the specific influences of air pollutants （PM10, SO2, and NO2） on hospital emergency admissions with different lag structures from 2009 to 2011, the sex and age specific influences of air pollution and the modifying effect of seasons on air pollution to analyze the possible interaction. Results It was found that a 10μg/m3 increase in concentration of PMlo at lag 03 day, SO2 and NO2 at lag 0 day were associated with an increase of 0.88%, 0.76%, and 1.82% respectively in overall emergency admissions. A 10 lag/m3 increase in concentration of PM10, SO2 and NO2 at lag 5 day were associated with an increase of 1.39%, 1.56%, and 1.18% respectively in cardiovascular disease emergency admissions. For lag 02, a 10 μg/m3 increase in concentration of PM10, SO2 and NO2 were associated with 1.72%, 1.34%, and 2.57% increases respectively in respiratory disease emergency admissions. Conclusion This study further confirmed that short-term exposure to ambient air pollution was associated with increased risk of hospital emergency admissions in Beijing.展开更多
AIM： To assess the combinative role of aflatoxin B1 （AFB1）, cyanobacterial toxins （cyanotoxins）, and hepatitis B virus （HBV） x gene in hepatotumorigenicity. METHODS： One-week-old animals carrying HBV x gene an...AIM： To assess the combinative role of aflatoxin B1 （AFB1）, cyanobacterial toxins （cyanotoxins）, and hepatitis B virus （HBV） x gene in hepatotumorigenicity. METHODS： One-week-old animals carrying HBV x gene and their wild-type littermates were intraperitoneally （ip） injected with either single-dose AFB1 [6 mg/kg body weight （bw）], repeated-dose cyanotoxins （microcystin- LR or nodularin, 10 μg/kg bw once a week for 15 wk）, DMSO （vehicle control） alone, or AFB1 followed by cyanotoxins a week later, and were sacrificed at 24 and 52 wk post-treatment. RESULTS： AFB1 induced liver tumors in 13 of 29 （44.8%） transcjenic mice at 52 wk post-treatment, significantly more frequent than in wild-type mice （13.3%）. This significant difference was not shown in the 24-wk study. Compared with AFB1 exposure alone, MC-LR and nodularin yielded approximately 3-fold and 6-fold increases in the incidence of AFB1-induced liver tumors in wild-type animals at 24 wk, respectively. HBV x gene did not further elevate the risk associated with coexposure to AFB1 and cyanotoxins. With the exception of an MC-LR-dosed wild-type mouse, no liver tumor was observed in mice treated with cyanotoxins alone at 24 wk. Neither DMSO-treated transgenic mice nor their wild-type littermates had pathologic alterations relevant to hepatotumorigenesis in even up to 52 wk. CONCLUSION： HBV x gene and nodularin promote the development of AFB1-induced liver tumors. Co-exposure to AFB1 and MC-LR tends to elevate the risk of liver tumors at 24 wk relative to exposure to one of them. The combinative effect of AFB1, cyanotoxins and HBVx on hepatotumorigenesis is weak at 24 wk.展开更多
We examined the attributed fractions of all-cause, cardiovascular, and respiratory mortality that were attributed to extreme and moderate cold and heat during 2010-2016 in Nanjing. Our results showed that 12.81%, 19.7...We examined the attributed fractions of all-cause, cardiovascular, and respiratory mortality that were attributed to extreme and moderate cold and heat during 2010-2016 in Nanjing. Our results showed that 12.81%, 19.78%, and 25.33% of all-cause, cardiovascular, and respiratory mortalities, respectively, were attributed to temperature. The highest attributed fractions for three types of mortality were at 4 ℃ and the attributed fractions were high around 4 ℃, which falls within the moderate cold temperatures. Although moderate cold has lower RR than extreme cold, it occurred on more days than did extreme cold. Therefore, health burden caused by moderate cold requires further attention in the future.展开更多
To unlearn the meaning of a sustainable water resource conservation is now an essential issue in using of sustained, sound, and high-quality water in the world. In this paper, a water quality purification by the Schum...To unlearn the meaning of a sustainable water resource conservation is now an essential issue in using of sustained, sound, and high-quality water in the world. In this paper, a water quality purification by the Schumann frequencies was first considered through the murmuring sound of upper reach at the mountain stream (Kyoto Pref., Japan) regarding the conservation of water resources. Second, water is changing freely and easily accepting the wavelength of all the sounds. We therefore referred to a flow and dynamic equilibrium to realize and understand the water quality purification process. Finally, a “consciousness only Buddhist philosophy” of water quality as an analogical approach was introduced to realize and understand the water purification process. As a result, we have confirmed the water purification capability by Schmann frequencies in an experiment on water quality. And through the experiment, we have realized the importance/significance to find the meaning for a person’s primary meaningless such as 1) meaning connection among life, environment, and economics as a condition of human life, 2) energy, entropy and fluctuation under law of thermodynamics, 3) a metaphor between water quality and mutual possession of the ten worlds based on conscious-only theory, and 4) sense of wonder through the water purification process.展开更多
This paper mainly investigated the value of the rainwater by introducing a “Logic of Encounter” that is a new logic beyond the logos and lemma through the metaphors which compare the real rainwater to one’s life. A...This paper mainly investigated the value of the rainwater by introducing a “Logic of Encounter” that is a new logic beyond the logos and lemma through the metaphors which compare the real rainwater to one’s life. A consideration regarding sustainable rainwater resource utilization has been described and the main results are summarized in the paper.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.82220108002 to F.C.and Grant No.82273737 to R.Z.)the U.S.National Institutes of Health(Grant Nos.CA209414,HL060710,and ES000002 to D.C.C.,Grant Nos.CA209414 and CA249096 to Y.L.)+1 种基金the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)supported by the Qing Lan Project of the Higher Education Institutions of Jiangsu Province and the Outstanding Young Level Academic Leadership Training Program of Nanjing Medical University.
文摘Interferon-related genes are involved in antiviral responses,inflammation,and immunity,which are closely related to sepsis-associated acute respiratory distress syndrome(ARDS).We analyzed 1972 participants with genotype data and 681 participants with gene expression data from the Molecular Epidemiology of ARDS(MEARDS),the Molecular Epidemiology of Sepsis in the ICU(MESSI),and the Molecular Diagnosis and Risk Stratification of Sepsis(MARS)cohorts in a three-step study focusing on sepsis-associated ARDS and sepsis-only controls.First,we identified and validated interferon-related genes associated with sepsis-associated ARDS risk using genetically regulated gene expression(GReX).Second,we examined the association of the confirmed gene(interferon regulatory factor 1,IRF1)with ARDS risk and survival and conducted a mediation analysis.Through discovery and validation,we found that the GReX of IRF1 was associated with ARDS risk(odds ratio[OR_(MEARDS)]=0.84,P=0.008;OR_(MESSI)=0.83,P=0.034).Furthermore,individual-level measured IRF1 expression was associated with reduced ARDS risk(OR=0.58,P=8.67×10^(-4)),and improved overall survival in ARDS patients(hazard ratio[HR_(28-day)]=0.49,P=0.009)and sepsis patients(HR_(28-day)=0.76,P=0.008).Mediation analysis revealed that IRF1 may enhance immune function by regulating the major histocompatibility complex,including HLA-F,which mediated more than 70%of protective effects of IRF1 on ARDS.The findings were validated by in vitro biological experiments including time-series infection dynamics,overexpression,knockout,and chromatin immunoprecipitation sequencing.Early prophylactic interventions to activate IRF1 in sepsis patients,thereby regulating HLA-F,may reduce the risk of ARDS and mortality,especially in severely ill patients.
基金supported by the National Natural Science Foundation of China(Nos.81973074,92043202,82204075,and 82204074).
文摘Carbon black(CB)is a vital constituent of airborne pollutants,comprising diesel exhaust and fine particulate matter(PM_(2.5)),aswell as a prevalent manufacturingmaterial.CBwas known to cause pulmonary dysfunction and fibrosis.However,the detailedmolecular mechanisms underlying fibrosis development are poorly understood.In this study,18 C57BL/6mice were randomized into two groups and exposed to CB and filtered air(FA)for 28 days,with 6 hr/day and 7 days perweek exposure regimen,respectively.The human normal bronchial epithelial cell line(BEAS-2B)was subjected to CB treatment for 24 h in vitro,with CB concentrations in 0,50,100,and 200μg/mL.Our study indicated that exposure to CB resulted in a reduction in lung function and the development of pulmonary fibrosis in mice.Furthermore,our results showed cytoskeleton rearrangement and epithelial-mesenchymal transition(EMT)phenotype in BEAS-2B cells were happened,after CB exposure.Subsequent studies revealed that elevated expression of THBS2 after CB primarily contributed to the development of pulmonary fibrosis.The research findings from both in vivo and in vitro studies provided evidence that piR-713551 was involved in CB exposure-induced EMT by targeting the THBS2 gene and activating theβ-catenin pathway.Mechanically,piR-713551/PIWIL4 complex activated the THBS2 transcription by recruitment of histone demethyltransferase KDM4A to reduce H3K9me3 modification at the THBS2 gene promoter.Conclusively,our research showed that CB exposure could activate EMT and lead pulmonary fibrosis which was modulated by piR-713551/PIWIL4 targeting THBS2.
基金supported by the National Natural Science Foundation of China(No.21976050)the Science and Technology Program of Hebei Province(No.21377779D)+3 种基金the Natural Science Foundation of Hebei Province(No.B2020206008)China Postdoctoral Science Foundation(Nos.2023M730317 and 2023T160066)the Fundamental Research Funds for the Central Universities(No.3332023042)the Open Project of Hebei Key Laboratory of Environment and Human Health(No.202301).
文摘Previous studies have suggested that abnormal hepatobiliary system function may contribute to poor prognosis in patientswith acute coronary syndrome(ACS)and that abnormal hepatobiliary system function may be associated with per-and polyfluoroalkyl substances(PFAS)exposure.However,there is limited evidence for this association in cardiovascular subpopulations,particularly in the ACS patients.Therefore,we performed this study to evaluate the association between plasma PFAS exposure and hepatobiliary system function biomarkers in patients with ACS.This study included 546 newly diagnosed ACS patients at the Second Hospital of Hebei Medical University,and data on 15 hepatobiliary system function biomarkers were obtained from medical records.Associations between single PFAS and hepatobiliary system function biomarkers were assessed using multiple linear regression models and restricted cubic spline model(RCS),and mixture effects were assessed using the Quantile g-computation model.The results showed that total bile acids(TBA)was negative associated with perfluorohexane sulfonic acid(PFHxS)(-7.69%,95%CI:-12.15%,-3.01%).According to the RCS model,linear associations were found between TBA and PFHxS(P for overall=0.003,P for non-linear=0.234).We also have observed the association between between PFAS congeners and liver enzyme such as aspartate aminotransferase(AST)and α-l-Fucosidase(AFU),but it was not statistically significant after correction.In addition,Our results also revealed an association between prealbumin(PA)and PFAS congeners as well as mixtures.Our findings have provided a piece of epidemiological evidence on associations between PFAS congeners or mixture,and serum hepatobiliary system function biomarkers in ACS patients,which could be a basis for subsequent mechanism studies.
基金supported by the China Postdoctoral Science Foundation(Nos.2023M730317 and 2023T160066)the Fundamental Research Funds for the Central Universities(No.3332023042)+3 种基金the Open Project of Hebei Key Laboratory of Environment and Human Health(No.202301)the Programs of the National Natural Science Foundation of China(No.21976050)the Science and Technology Program of Hebei Province(No.21377779D)the Natural Science Foundation of Hebei Province,China(No.B2020206008).
文摘Although per-and polyfluoroalkyl substances(PFAS)have been frequently linked to cardiovascular and renal disease separately,evidence remains scarce regarding their systematic effect.Therefore,we recruited 546 newly diagnosed acute coronary syndrome(ACS)patients and detected seven myocardial enzymes and six kidney function biomarkers.Twelve PFASwere also assessedwith ultra-high-performance liquid chromatography-tandem mass spectrometry.Generalized linear model and restricted cubic spline model were applied to single pollutant analysis.Quantile g-computation was used for mixture analysis.Network model was utilized to identify central and bridge nodes of pollutants and phenotypes.In the present study,perfluorohexane sulfonic acid was positively associated with uric acid(UA)(β=0.04,95%confidence interval(CI):0.01,0.07),and perfluorobutanoic acid was negatively associated with estimated glomerular filtration rate(β=-0.04,95%CI:-0.07,-0.01)but positively associated with UA(β=0.03,95%CI:0.01,0.06).In mixture analysis,each quantile increase in the PFAS mixture was significantly associated with UA(β=0.08,95%CI:0.04,0.11).Network analysis revealed that perfluorooctanoate,UA,and myoglobin were denoted as bridge nodes,and the first principal component of lactate dehydrogenase and creatine kinase-myocardial band was identified as the node with the highest strength and expected influence.This study investigates the systematic impact of PFAS exposure through cardiorenal interaction network,which highlights that PFAS may serve as an upstream approach in UA-modulated cardiorenal network to affect cardiorenal system comprehensively.
基金funded by the National Natural Science Foundation of China(Grant Nos.82220108002 to F.C.,82273737 to R.Z.,82473728 to Y.W.)the US National Institutes of Health(Grant Nos.CA209414,HL060710,ES000002 to D.C.C.,CA209414,CA249096 to Y.L.)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).R.Z.was partially supported by the Qing Lan Project of the Higher Education Institutions of Jiangsu Province and the Outstanding Young-Level Academic Leadership Training Program of Nanjing Medical University.
文摘Emerging evidence highlights the role of thyroid hormones in cancer,although findings are controversial.Research on thyroid-related traits in lung carcinogenesis is limited.Using UK Biobank data,we performed bidirectional Mendelian randomization(MR)to assess causal associations between lung cancer risk and thyroid dysfunction(hypothyroidism and hyperthyroidism)or functional traits(free thyroxine[FT4]and normal-range thyroid-stimulating hormone[TSH]).Furthermore,in the smoking-behavior-stratified MR analysis,we evaluated the mediating effect of thyroid-related phenotypes on the association between smoking behaviors and lung cancer.We demonstrated significant associations between lung cancer risk and hypothyroidism(hazard ratio[HR]=1.14,95%confidence interval[CI]=1.03–1.26,P=0.009)and hyperthyroidism(HR=1.55,95%CI=1.29–1.87,P=1.90×10^(-6))in the UKB.Moreover,the MR analysis indicated a causal effect of thyroid dysfunction on lung cancer risk(ORinverse variance weighted[IVW]=1.09,95%CI=1.05–1.13,P=3.12×10^(-6)for hypothyroidism;ORIVW=1.08,95%CI=1.04–1.12,P=8.14×10^(-5)for hyperthyroidism).We found that FT4 levels were protective against lung cancer risk(ORIVW=0.93,95%CI=0.87–0.99,P=0.030).Additionally,the stratified MR analysis demonstrated distinct causal effects of thyroid dysfunction on lung cancer risk among smokers.Hyperthyroidism mediated the effect of smoking behaviors,especially the age of smoking initiation(17.66%mediated),on lung cancer risk.Thus,thyroid dysfunction phenotypes play causal roles in lung cancer development exclusively among smokers and act as mediators in the causal pathway from smoking to lung cancer.
基金supported by the National Natural Science Foundation of China(No.82404365)the Noncommunicable Chronic Diseases-National Science and Technology Major Project(No.2023ZD0513200)+7 种基金China Medical Board(No.15-230)China Postdoctoral Science Foundation(Nos.2023M730317and 2023T160066)the Fundamental Research Funds for the Central Universities(No.3332023042)the Open Project of Hebei Key Laboratory of Environment and Human Health(No.202301)the National Key Research and Development Program of China(No.2022YFC3703000)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(No.2022-JKCS-11)the CAMS Innovation Fund for Medical Sciences(No.2022-I2M-JB-003)the Programs of the National Natural Science Foundation of China(No.21976050).
文摘Associations of per-and polyfluoroalkyl substances(PFAS)on lipid metabolism have been documented but research remains scarce regarding effect of PFAS on lipid variability.To deeply understand their relationship,a step-forward in causal inference is expected.To address these,we conducted a longitudinal study with three repeated measurements involving 201 participants in Beijing,among which 100 eligible participants were included for the present study.Twenty-three PFAS and four lipid indicators were assessed at each visit.We used linear mixed models and quantile g-computation models to investigate associations between PFAS and blood lipid levels.A latent class growth model described PFAS serum exposure patterns,and a generalized linear model demonstrated associations between these patterns and lipid variability.Our study found that PFDA was associated with increased TC(β=0.083,95%CI:0.011,0.155)and HDL-C(β=0.106,95%CI:0.034,0.178).The PFAS mixture also showed a positive relationship with TC(β=0.06,95%CI:0.02,0.10),with PFDA contributing most positively.Compared to the low trajectory group,the middle trajectory group for PFDA was associated with VIM of TC(β=0.756,95%CI:0.153,1.359).Furthermore,PFDA showed biological gradientswith lipid metabolism.This is the first repeated-measures study to identify the impact of PFAS serum exposure pattern on the lipid metabolism and the first to estimate the association between PFAS and blood lipid levels in middle-aged and elderly Chinese and reinforce the evidence of their causal relationship through epidemiological studies.
基金funded by grants from Project supported by the Funds for Noncommunicable Chronic Diseases-National Science and Technology Major Project(No.2024ZD0520000,2024ZD0520003)Noncommunicable Chronic Diseases-National Science and Technology Major Project(No.2024ZD0524400,2024ZD0524403)+2 种基金National Natural Science Foundation of China(No.82388102)Jiangsu Medical Association Medical Research Project of Health Management,SYH-32099-0119(No.2024023)the Specialized Diseases Clinical Research Fund of Jiangsu Province Hospital(No.DL202411)。
文摘Objective:This study aimed to construct a model that predicts invasive lung cancer using longitudinal radiological features from multiple low-dose computed tomography(LDCT)scans,thereby addressing overdiagnosis in lung cancer screening.Methods:In this retrospective study,628 patients with pulmonary nodules who underwent three LDCT scans followed by surgical resection were categorized into invasive carcinoma(n=155)and non-invasive nodule(n=473)groups on the basis of pathological diagnosis.This derivation aimed to identify risk factors and construct a multivariate logistic model.The predictive performance was externally validated in two independent cohorts(retrospectively designed,n=252;prospectively designed,n=269).The discrimination and calibration of the model were evaluated using area under the curve(AUC),and calibration plots.Decision curve analysis(DCA)was further performed to evaluate the net benefit in practical clinical scenarios.Results:The model,termed multiple CTs-invasive lung cancer(MCT-ILC),incorporated eleven factors encompassing nodule features at baseline and feature variability during follow-up.The standard deviation of diameter variability(SD_(diameter))was the most reliable predictor,with an odds ratio[95% confidence interval(95%CI)of 7.35(5.32-10.16)(P<0.001)].AUCs with 95% CIs for the MCT-ILC model were 0.912(0.864-0.960)and 0.906(0.833-0.979)in the two testing cohorts and were superior to those for the model containing only features at baseline(PD_(elong)=0.002 and 0.021,respectively).For calibration,the Brier scores of the MCT-ILC model were0.091(95% CI:0.064-0.118) and 0.078(95% CI:0.055-0.101)in the two test sets.The decision curve image showed that the MCT-ILC model was the only model that maintained positive net benefits across the entire threshold range.Furthermore,the MCT-ILC model score could classify more than 90% of patients with invasive nodules into the high-risk group.Conclusions:The MCT-ILC model could assess pulmonary nodule invasiveness,potentially mitigating overdiagnosis in lung cancer screening.
文摘目的:探讨食管癌高发区——淮安市楚州区居民的食管癌危险因素。方法:采用以人群为基础的1?2匹配的病例对照研究方法,用专门设计的调查表对207例食管癌病例及414例正常对照者进行1对1的询问调查,采用条件logistic回归分析法对所获得的调查资料进行统计学分析。结果:人均月收入低、体质指数(body mass index,BMI)偏低、既往食管病变、不按时就餐、10年前喜食辣食、10年前喜食烫食、喜食肥肉、不食大蒜和肿瘤家族史等可能是食管癌的危险因素。结论:饮食习惯、人均月收入、既往食管病变等因素可影响食管癌的发生,应针对相关危险因素采取相应的预防措施。
文摘Objective To estimate the burden of cirrhosis and other chronic liver diseases caused by specific etiologies in China.Methods Data from the Global Burden of Disease Study 2016(GBD 2016)were used.We evaluated the burden by analyzing age-sex-province-specific prevalence,mortality,and disability-adjusted lifeyears(DALYs)of 33 provinces in China.Results From 1990 to 2016,prevalence cases in thousands increased by 73.7%from 6833.3(95%UI:6498.0–7180.6)to 11869.6(95%UI:11274.6–12504.7).Age-standardized mortality and DALY rates per100,000 decreased by 51.2%and 53.3%,respectively.Male and elderly people(aged≥60 years)preponderance were found for prevalence,mortality,and DALYs.The number of prevalence cases,deaths,and DALYs due to hepatitis C virus(HCV)increased by 86.6%,8.7%,and 0.9%,respectively.Also,age-standardized prevalence rates decreased in 31 provinces,but increased in Yunnan and Shandong.The Socio-demographic Index(SDI)values were negatively correlated with age-standardized mortality and DALY rates by provinces in 2016;the correlation coefficients were-0.817 and-0.828,respectively.Conclusion Cirrhosis and other chronic liver diseases remain a huge health burden in China,with the increase of population and the aging of population.Hepatitis B virus(HBV)remains the leading cause of the health burden in China.
基金supported by the Gong-Yi Program of China Meteorological Administration(GYHY201106034)the Fundamental Research Funds for the Central Universities(lzuibky-2013-m03)+2 种基金National Natural Science Foundation of China(41075103)National Natural Science Foundation of China(41075102)National Natural Science Foundation of China(41305105)
文摘Objective To investigate the association between ambient air pollution and hospital emergency admissions in Beijing. Methods In this study, a semi-parametric generalized additive model （GAM） was used to evaluate the specific influences of air pollutants （PM10, SO2, and NO2） on hospital emergency admissions with different lag structures from 2009 to 2011, the sex and age specific influences of air pollution and the modifying effect of seasons on air pollution to analyze the possible interaction. Results It was found that a 10μg/m3 increase in concentration of PMlo at lag 03 day, SO2 and NO2 at lag 0 day were associated with an increase of 0.88%, 0.76%, and 1.82% respectively in overall emergency admissions. A 10 lag/m3 increase in concentration of PM10, SO2 and NO2 at lag 5 day were associated with an increase of 1.39%, 1.56%, and 1.18% respectively in cardiovascular disease emergency admissions. For lag 02, a 10 μg/m3 increase in concentration of PM10, SO2 and NO2 were associated with 1.72%, 1.34%, and 2.57% increases respectively in respiratory disease emergency admissions. Conclusion This study further confirmed that short-term exposure to ambient air pollution was associated with increased risk of hospital emergency admissions in Beijing.
基金Supported by the Key Project of National Natural Science Foundation of China, No. 39730380
文摘AIM： To assess the combinative role of aflatoxin B1 （AFB1）, cyanobacterial toxins （cyanotoxins）, and hepatitis B virus （HBV） x gene in hepatotumorigenicity. METHODS： One-week-old animals carrying HBV x gene and their wild-type littermates were intraperitoneally （ip） injected with either single-dose AFB1 [6 mg/kg body weight （bw）], repeated-dose cyanotoxins （microcystin- LR or nodularin, 10 μg/kg bw once a week for 15 wk）, DMSO （vehicle control） alone, or AFB1 followed by cyanotoxins a week later, and were sacrificed at 24 and 52 wk post-treatment. RESULTS： AFB1 induced liver tumors in 13 of 29 （44.8%） transcjenic mice at 52 wk post-treatment, significantly more frequent than in wild-type mice （13.3%）. This significant difference was not shown in the 24-wk study. Compared with AFB1 exposure alone, MC-LR and nodularin yielded approximately 3-fold and 6-fold increases in the incidence of AFB1-induced liver tumors in wild-type animals at 24 wk, respectively. HBV x gene did not further elevate the risk associated with coexposure to AFB1 and cyanotoxins. With the exception of an MC-LR-dosed wild-type mouse, no liver tumor was observed in mice treated with cyanotoxins alone at 24 wk. Neither DMSO-treated transgenic mice nor their wild-type littermates had pathologic alterations relevant to hepatotumorigenesis in even up to 52 wk. CONCLUSION： HBV x gene and nodularin promote the development of AFB1-induced liver tumors. Co-exposure to AFB1 and MC-LR tends to elevate the risk of liver tumors at 24 wk relative to exposure to one of them. The combinative effect of AFB1, cyanotoxins and HBVx on hepatotumorigenesis is weak at 24 wk.
基金supported by the National key Research and Development Program of China [2016YFA0602004]the National Natural Science Foundation of China [91644226]+1 种基金the Chengdu University of Information Technology scientific research fund [KYTZ201713]Sichuan Provincial Department of Education scientific research fund [2018Z114]
文摘We examined the attributed fractions of all-cause, cardiovascular, and respiratory mortality that were attributed to extreme and moderate cold and heat during 2010-2016 in Nanjing. Our results showed that 12.81%, 19.78%, and 25.33% of all-cause, cardiovascular, and respiratory mortalities, respectively, were attributed to temperature. The highest attributed fractions for three types of mortality were at 4 ℃ and the attributed fractions were high around 4 ℃, which falls within the moderate cold temperatures. Although moderate cold has lower RR than extreme cold, it occurred on more days than did extreme cold. Therefore, health burden caused by moderate cold requires further attention in the future.
文摘To unlearn the meaning of a sustainable water resource conservation is now an essential issue in using of sustained, sound, and high-quality water in the world. In this paper, a water quality purification by the Schumann frequencies was first considered through the murmuring sound of upper reach at the mountain stream (Kyoto Pref., Japan) regarding the conservation of water resources. Second, water is changing freely and easily accepting the wavelength of all the sounds. We therefore referred to a flow and dynamic equilibrium to realize and understand the water quality purification process. Finally, a “consciousness only Buddhist philosophy” of water quality as an analogical approach was introduced to realize and understand the water purification process. As a result, we have confirmed the water purification capability by Schmann frequencies in an experiment on water quality. And through the experiment, we have realized the importance/significance to find the meaning for a person’s primary meaningless such as 1) meaning connection among life, environment, and economics as a condition of human life, 2) energy, entropy and fluctuation under law of thermodynamics, 3) a metaphor between water quality and mutual possession of the ten worlds based on conscious-only theory, and 4) sense of wonder through the water purification process.
文摘This paper mainly investigated the value of the rainwater by introducing a “Logic of Encounter” that is a new logic beyond the logos and lemma through the metaphors which compare the real rainwater to one’s life. A consideration regarding sustainable rainwater resource utilization has been described and the main results are summarized in the paper.
