Epidemiological data are scarce regarding the association of exposure to mixtures of per-and polyfluoroalkyl substances(PFASs)with liver injury in the general population.In the current study,therefore,we examined data...Epidemiological data are scarce regarding the association of exposure to mixtures of per-and polyfluoroalkyl substances(PFASs)with liver injury in the general population.In the current study,therefore,we examined data from the National Health and Nutrition Examination Survey(2009–2018).The PFAS exposure levels were defined by the serum concentrations of PFASs with over 70%detection in samples,namely perfluorooctanoic acid,perfluorononanoic acid,perfluorohexane sulfonic acid,perfluorodecanoic acid,and perfluorooctane sulfonic acid(PFOS).We evaluated liver injury from two aspects:first,the degree of liver inflammation was determined based on levels of the serum alanine aminotransferase,aspartate aminotransferase,glutamyltransferase,and total bilirubin;second,the degree of liver fibrosis was determined based on the fibrosis-4 index.We assessed the associations of individual or total PFAS exposure with these liver injury outcomes using multivariable linear and logistic regression models,restricted cubic splines,and weighted quantile sum regression.Among the samples of 7484 American adults,the median concentration of PFOS was the highest,followed by perfluorooctanoic acid and perfluorohexane sulfonic acid.Using multivariable linear regression,we observed positive correlations between all PFAS exposure and liver enzyme levels,such as alanine aminotransferase,aspartate aminotransferase,and total bilirubin.Additionally,the weighted quantile sum model indicated an overall positive association between exposure to the five PFASs and liver injury risk.For liver function biomarkers and liver fibrosis,perfluorononanoic acid and PFOS were the most heavily weighted chemicals,respectively.Our findings provide new epidemiological evidence indicating potential associations between PFAS exposure and adverse effects on liver injury biomarkers,highlighting the potentially harmful effects of PFAS exposure on human liver health.展开更多
Objective The study aimed to investigate the impact of rare earth elements(REEs)exposure on pregnancy outcomes of in vitro fertilization-embryo transfer(IVF-ET)by analyzing samples from spouses.Methods A total of 141 ...Objective The study aimed to investigate the impact of rare earth elements(REEs)exposure on pregnancy outcomes of in vitro fertilization-embryo transfer(IVF-ET)by analyzing samples from spouses.Methods A total of 141 couples were included.Blood and follicular fluid from the wives and semen plasma from the husbands,were analyzed for REEs using inductively coupled plasma mass spectrometry(ICP-MS).Spearman's correlation coefficients and the Mann–Whitney U test were used to assess correlations and compare REE concentrations among three types of samples,respectively.Logistic models were utilized to estimate the individual REE effect on IVF-ET outcomes,while BKMR and WQS models explored the mixture of REE interaction effects on IVF-ET outcomes.Results Higher La concentration in semen(median 0.089 ng/mL,P=0.03)was associated with a lower fertilization rate.However,this effect was not observed after artificial selection intervention through intracytoplasmic sperm injection(ICSI)(P=0.27).In semen,the REEs mixture did not exhibit any significant association with clinical pregnancy.Conclusion Our study revealed a potential association between high La exposure in semen and a decline in fertilization rate,but not clinical pregnancy rate.This is the first to report REEs concentrations in follicular fluid with La,Ce,Pr,and Nd found at significantly lower concentrations than in serum,suggesting that these four REEs may not accumulate in the female reproductive system.However,at the current exposure levels,mixed REEs exposure did not exhibit reproductive toxicity.展开更多
Background and Aims:Age-related mosaic chromosomal alterations(mCAs)detected from genotyping of blood-de-rived DNA are structural somatic variants that indicate clonal hematopoiesis.This study aimed to investigate whe...Background and Aims:Age-related mosaic chromosomal alterations(mCAs)detected from genotyping of blood-de-rived DNA are structural somatic variants that indicate clonal hematopoiesis.This study aimed to investigate whether mCAs contribute to the risk of cirrhosis and modify the effect of a polygenic risk score(PRS)on cirrhosis risk prediction.Methods:mCA call sets of individuals with European ancestry were obtained from the UK Biobank.The PRS was constructed based on 12 susceptible single-nucleotide poly-morphisms for cirrhosis.Cox proportional hazard models were applied to evaluate the associations between mCAs and cirrhosis risk.Results:Among 448,645 individuals with a median follow-up of 12.5 years,we identified 2,681 cas-es of cirrhosis,1,775 cases of compensated cirrhosis,and 1,706 cases of decompensated cirrhosis.Compared to non-carriers,individuals with copy-neutral loss of heterozygosity mCAs had a significantly increased risk of cirrhosis(hazard ratio(HR)1.42,95%confidence interval(CI)1.12-1.81).This risk was higher in patients with expanded cell fractions of mCAs(cell fractions≥10%vs.cell fractions<10%),especially for the risk of decompensated cirrhosis(HR 2.03[95%CI 1.09-3.78]vs.1.14[0.80-1.64]).In comparison to non-carriers of mCAs with low genetic risk,individuals with expanded copy-neutral loss of heterozygosity and high genetic risk showed the highest cirrhosis risk(HR5.39[95%CI 2.41-12.07]).Conclusions:The presence of mCAs is associated with increased susceptibility to cirrhosis risk and could be combined with PRS for personalized cirrhosis risk stratification.展开更多
In China,the medical guidelines recommend performing noninvasive prenatal testing(NIPT)with caution for pregnant women aged 35 years or older.However,the Mother and Child Health Care Law suggests that all primiparous ...In China,the medical guidelines recommend performing noninvasive prenatal testing(NIPT)with caution for pregnant women aged 35 years or older.However,the Mother and Child Health Care Law suggests that all primiparous women whose age is older than 35 years undergo prenatal diagnosis.These two inconsistent suggestions/recommendations have made obstetricians confused about whether to offer NIPT to these older pregnant women.To face this issue and find out the solution we performed a retrospective study of 189,809 NIPT samples collected from 28 provincial-leveled administrative units in China.Of 1,564 women with high-risk pregnancies who underwent NIPT,459(29.3%)did not participate in follow-up.The compound sensitivity and specificity of NIPT for trisomies 21,18 and 13 detection was 99.1%(95%CI,98.0%–99.6%)and 99.9%(95%CI,98.8%–99.9%),respectively.In secundiparous women,NIPT showed high sensitivity and specificity similar to that in primiparous women.The observed risk for trisomies 21 and 18 significantly increased when the maternal age was 39 and older.After the publication of the current NIPT policy,the follow-up rate at our center was 97.9%;however,a large number of women are not in maternal and infant care networks nationwide,and that makes the follow-up rate outside our center relatively low.Our study shows that to balance the prevention of major aneuploidies and the limited resources for prenatal diagnosis,the cut-off age of 35 for invasive prenatal diagnosis might be unnecessary.Although the NIPT guidelines are well written,how to practice it effectively,especially in less industrialized areas,is worth discussing.展开更多
文摘Epidemiological data are scarce regarding the association of exposure to mixtures of per-and polyfluoroalkyl substances(PFASs)with liver injury in the general population.In the current study,therefore,we examined data from the National Health and Nutrition Examination Survey(2009–2018).The PFAS exposure levels were defined by the serum concentrations of PFASs with over 70%detection in samples,namely perfluorooctanoic acid,perfluorononanoic acid,perfluorohexane sulfonic acid,perfluorodecanoic acid,and perfluorooctane sulfonic acid(PFOS).We evaluated liver injury from two aspects:first,the degree of liver inflammation was determined based on levels of the serum alanine aminotransferase,aspartate aminotransferase,glutamyltransferase,and total bilirubin;second,the degree of liver fibrosis was determined based on the fibrosis-4 index.We assessed the associations of individual or total PFAS exposure with these liver injury outcomes using multivariable linear and logistic regression models,restricted cubic splines,and weighted quantile sum regression.Among the samples of 7484 American adults,the median concentration of PFOS was the highest,followed by perfluorooctanoic acid and perfluorohexane sulfonic acid.Using multivariable linear regression,we observed positive correlations between all PFAS exposure and liver enzyme levels,such as alanine aminotransferase,aspartate aminotransferase,and total bilirubin.Additionally,the weighted quantile sum model indicated an overall positive association between exposure to the five PFASs and liver injury risk.For liver function biomarkers and liver fibrosis,perfluorononanoic acid and PFOS were the most heavily weighted chemicals,respectively.Our findings provide new epidemiological evidence indicating potential associations between PFAS exposure and adverse effects on liver injury biomarkers,highlighting the potentially harmful effects of PFAS exposure on human liver health.
基金supported by the National Key Research and Development Program of China(2022YFC2702900 and 2021YFC2701103)National Natural Science Foundation of China(82171654)。
文摘Objective The study aimed to investigate the impact of rare earth elements(REEs)exposure on pregnancy outcomes of in vitro fertilization-embryo transfer(IVF-ET)by analyzing samples from spouses.Methods A total of 141 couples were included.Blood and follicular fluid from the wives and semen plasma from the husbands,were analyzed for REEs using inductively coupled plasma mass spectrometry(ICP-MS).Spearman's correlation coefficients and the Mann–Whitney U test were used to assess correlations and compare REE concentrations among three types of samples,respectively.Logistic models were utilized to estimate the individual REE effect on IVF-ET outcomes,while BKMR and WQS models explored the mixture of REE interaction effects on IVF-ET outcomes.Results Higher La concentration in semen(median 0.089 ng/mL,P=0.03)was associated with a lower fertilization rate.However,this effect was not observed after artificial selection intervention through intracytoplasmic sperm injection(ICSI)(P=0.27).In semen,the REEs mixture did not exhibit any significant association with clinical pregnancy.Conclusion Our study revealed a potential association between high La exposure in semen and a decline in fertilization rate,but not clinical pregnancy rate.This is the first to report REEs concentrations in follicular fluid with La,Ce,Pr,and Nd found at significantly lower concentrations than in serum,suggesting that these four REEs may not accumulate in the female reproductive system.However,at the current exposure levels,mixed REEs exposure did not exhibit reproductive toxicity.
基金supported by the Jiangsu Province Capability Improvement Project through Science,Technology and Education(grant number:ZDXK202248,recipient:QZ)National Natural Science Foundation of China(grant number:82373654,recipient:CS)+2 种基金Science and Technology Young Scientific and Technological Talents Project of Jiangsu Province(grant number:2021-50,recipient:CS)Key project of Changzhou Medical Center,Nanjing Medical University(grant number:CZKYCMCM202210,recipient:CS)Chinese Academy of Medical Sciences(grant number:2019RU038,recipient:CS).
文摘Background and Aims:Age-related mosaic chromosomal alterations(mCAs)detected from genotyping of blood-de-rived DNA are structural somatic variants that indicate clonal hematopoiesis.This study aimed to investigate whether mCAs contribute to the risk of cirrhosis and modify the effect of a polygenic risk score(PRS)on cirrhosis risk prediction.Methods:mCA call sets of individuals with European ancestry were obtained from the UK Biobank.The PRS was constructed based on 12 susceptible single-nucleotide poly-morphisms for cirrhosis.Cox proportional hazard models were applied to evaluate the associations between mCAs and cirrhosis risk.Results:Among 448,645 individuals with a median follow-up of 12.5 years,we identified 2,681 cas-es of cirrhosis,1,775 cases of compensated cirrhosis,and 1,706 cases of decompensated cirrhosis.Compared to non-carriers,individuals with copy-neutral loss of heterozygosity mCAs had a significantly increased risk of cirrhosis(hazard ratio(HR)1.42,95%confidence interval(CI)1.12-1.81).This risk was higher in patients with expanded cell fractions of mCAs(cell fractions≥10%vs.cell fractions<10%),especially for the risk of decompensated cirrhosis(HR 2.03[95%CI 1.09-3.78]vs.1.14[0.80-1.64]).In comparison to non-carriers of mCAs with low genetic risk,individuals with expanded copy-neutral loss of heterozygosity and high genetic risk showed the highest cirrhosis risk(HR5.39[95%CI 2.41-12.07]).Conclusions:The presence of mCAs is associated with increased susceptibility to cirrhosis risk and could be combined with PRS for personalized cirrhosis risk stratification.
基金supported by grants from the National Key Technology R&D Program (2015BAI13B06).
文摘In China,the medical guidelines recommend performing noninvasive prenatal testing(NIPT)with caution for pregnant women aged 35 years or older.However,the Mother and Child Health Care Law suggests that all primiparous women whose age is older than 35 years undergo prenatal diagnosis.These two inconsistent suggestions/recommendations have made obstetricians confused about whether to offer NIPT to these older pregnant women.To face this issue and find out the solution we performed a retrospective study of 189,809 NIPT samples collected from 28 provincial-leveled administrative units in China.Of 1,564 women with high-risk pregnancies who underwent NIPT,459(29.3%)did not participate in follow-up.The compound sensitivity and specificity of NIPT for trisomies 21,18 and 13 detection was 99.1%(95%CI,98.0%–99.6%)and 99.9%(95%CI,98.8%–99.9%),respectively.In secundiparous women,NIPT showed high sensitivity and specificity similar to that in primiparous women.The observed risk for trisomies 21 and 18 significantly increased when the maternal age was 39 and older.After the publication of the current NIPT policy,the follow-up rate at our center was 97.9%;however,a large number of women are not in maternal and infant care networks nationwide,and that makes the follow-up rate outside our center relatively low.Our study shows that to balance the prevention of major aneuploidies and the limited resources for prenatal diagnosis,the cut-off age of 35 for invasive prenatal diagnosis might be unnecessary.Although the NIPT guidelines are well written,how to practice it effectively,especially in less industrialized areas,is worth discussing.