Objective Thyroid hormones(THs)regulate multiple physiological activities in the liver,including cellular metabolism,differentiation,and cell growth,and play important roles in the pathogenesis of hepatocellular carci...Objective Thyroid hormones(THs)regulate multiple physiological activities in the liver,including cellular metabolism,differentiation,and cell growth,and play important roles in the pathogenesis of hepatocellular carcinoma(HCC).Thyroid peroxidase(TPO)is a key molecule involved in the THs synthesis and signaling pathway.As an epigenetic modification,DNA methylation has a critical role in tumorigenesis with diagnostic potential.However,the connection between THs and DNA methylation has been rarely investigated.Methods The methylation of key TH-related genes was analyzed by in-house epigenome-wide scanning,and we further analyzed the methylation levels of the TPO promotor in 164 sample pairs of HCC and adjacent non-cancerous tissues by Sequenom EpiTYPER assays,and evaluated their clinical implications.Results We identified that the methylation of the TPO promoter was downregulated in the HCC tissues(P<0.0001)with a mean difference ranging from 18.5%to 22.3%.This methylation pattern correlated with several clinical factors,including a multi-satellite tumor,fibrous capsule,and the presence of tumor thrombus.The receiver operator characteristic(ROC)curve analysis further confirmed that the percent methylated reference(PMR)values for TPO were predictive of the tumor[the area under the curve(AUC)ranged from 0.755 to 0.818]and the thrombosis in the HCC patients(the AUC ranged from 0.706 to 0.777).Conclusion These findings demonstrated that epigenetic alterations of TPO,as indicated by the PMR values,were a potential biomarker for HCC patients with tumor thrombosis.展开更多
Background:Graves'ophthalmopathy(GO)occurs commonly in children with Graves'disease(GD).However,there are limited studies on the clinical manifestations and thyroid autoantibodies in pediatric GO.The aim of th...Background:Graves'ophthalmopathy(GO)occurs commonly in children with Graves'disease(GD).However,there are limited studies on the clinical manifestations and thyroid autoantibodies in pediatric GO.The aim of this study was to investigate the prevalence and risk factors of GO in childhood GD.Methods:Clinical and biochemical data from children and adolescents with GD were retrospectively reviewed.Eighty patients under 19 years of age were included in the present study.We compared the clinical and biochemical differences between patients with and without GO.Results:Thirty-nine percent of the patients had GO,and 81%of the GO patients were females.Of these,two patients showed unilateral GO.Triiodothyronine(T3)levels were higher in GO patients than in those without GO.Anti-thyroglobulin antibody and thyroid stimulating hormone receptor antibody titers were not significantly different between the two groups.Anti-thyroid peroxidase antibody(TPO Ab)positivity was 68%in the patients with GO and only 47%in the patients without GO.In multivariate regression analysis,high T3 levels and TPO Ab positivity were related to the presence of GO.Conclusion:In children and adolescents with GD,TPO Ab positivity and high T3 levels could act as predictive factors for the presence of GO.展开更多
Many per-and polyfluoralkyl substances(PFASs)may disrupt maternal thyroid hormone homeostasis in pregnancy.Concerns should be raised regarding the PFASs exposure in pregnant women because thyroid hormones are involved...Many per-and polyfluoralkyl substances(PFASs)may disrupt maternal thyroid hormone homeostasis in pregnancy.Concerns should be raised regarding the PFASs exposure in pregnant women because thyroid hormones are involved in the early development of the fetus.In this study,we measured the concentrations of 13 PFASs,including five novel shortchain PFASs,in serum from 123 pregnant women in Beijing,China.Linear regression models were used to investigate the association between thyroid-stimulating hormone(TSH)or free thyroxine(FT4)levels and PFASs concentrations under consideration of the impacts of pregnancy-induced physiological factors.We found that perfluorobutanoic acid(PFBA)(β=0.189,95%CI=-0.039,0.417,p=0.10)and perfluorodecanoic acid(PFDA)(β=-0.554,95%CI=-1.16,0.049,p=0.071)were suggestive of significant association with TSH in thyroid peroxidase antibody(TPOAb)negative women.No association was observed between all PFASs and FT4 levels after controlling for these confounding factors,such as BMI,gestational weight gain and maternal age.These findings suggest that it should pay more attention to the association between thyroid hormone levels and short-chain PFASs concentrations.Future studies could consider a greater sample and the inclusion of other clinical indicators of thyroid function,such as free T3 and total T3.展开更多
文摘Objective Thyroid hormones(THs)regulate multiple physiological activities in the liver,including cellular metabolism,differentiation,and cell growth,and play important roles in the pathogenesis of hepatocellular carcinoma(HCC).Thyroid peroxidase(TPO)is a key molecule involved in the THs synthesis and signaling pathway.As an epigenetic modification,DNA methylation has a critical role in tumorigenesis with diagnostic potential.However,the connection between THs and DNA methylation has been rarely investigated.Methods The methylation of key TH-related genes was analyzed by in-house epigenome-wide scanning,and we further analyzed the methylation levels of the TPO promotor in 164 sample pairs of HCC and adjacent non-cancerous tissues by Sequenom EpiTYPER assays,and evaluated their clinical implications.Results We identified that the methylation of the TPO promoter was downregulated in the HCC tissues(P<0.0001)with a mean difference ranging from 18.5%to 22.3%.This methylation pattern correlated with several clinical factors,including a multi-satellite tumor,fibrous capsule,and the presence of tumor thrombus.The receiver operator characteristic(ROC)curve analysis further confirmed that the percent methylated reference(PMR)values for TPO were predictive of the tumor[the area under the curve(AUC)ranged from 0.755 to 0.818]and the thrombosis in the HCC patients(the AUC ranged from 0.706 to 0.777).Conclusion These findings demonstrated that epigenetic alterations of TPO,as indicated by the PMR values,were a potential biomarker for HCC patients with tumor thrombosis.
文摘Background:Graves'ophthalmopathy(GO)occurs commonly in children with Graves'disease(GD).However,there are limited studies on the clinical manifestations and thyroid autoantibodies in pediatric GO.The aim of this study was to investigate the prevalence and risk factors of GO in childhood GD.Methods:Clinical and biochemical data from children and adolescents with GD were retrospectively reviewed.Eighty patients under 19 years of age were included in the present study.We compared the clinical and biochemical differences between patients with and without GO.Results:Thirty-nine percent of the patients had GO,and 81%of the GO patients were females.Of these,two patients showed unilateral GO.Triiodothyronine(T3)levels were higher in GO patients than in those without GO.Anti-thyroglobulin antibody and thyroid stimulating hormone receptor antibody titers were not significantly different between the two groups.Anti-thyroid peroxidase antibody(TPO Ab)positivity was 68%in the patients with GO and only 47%in the patients without GO.In multivariate regression analysis,high T3 levels and TPO Ab positivity were related to the presence of GO.Conclusion:In children and adolescents with GD,TPO Ab positivity and high T3 levels could act as predictive factors for the presence of GO.
基金supported by the National Key R&D Program of China (No. 2018YFA0901200)the National Natural Science Foundation of China (Nos. 21876194 and 21677170)
文摘Many per-and polyfluoralkyl substances(PFASs)may disrupt maternal thyroid hormone homeostasis in pregnancy.Concerns should be raised regarding the PFASs exposure in pregnant women because thyroid hormones are involved in the early development of the fetus.In this study,we measured the concentrations of 13 PFASs,including five novel shortchain PFASs,in serum from 123 pregnant women in Beijing,China.Linear regression models were used to investigate the association between thyroid-stimulating hormone(TSH)or free thyroxine(FT4)levels and PFASs concentrations under consideration of the impacts of pregnancy-induced physiological factors.We found that perfluorobutanoic acid(PFBA)(β=0.189,95%CI=-0.039,0.417,p=0.10)and perfluorodecanoic acid(PFDA)(β=-0.554,95%CI=-1.16,0.049,p=0.071)were suggestive of significant association with TSH in thyroid peroxidase antibody(TPOAb)negative women.No association was observed between all PFASs and FT4 levels after controlling for these confounding factors,such as BMI,gestational weight gain and maternal age.These findings suggest that it should pay more attention to the association between thyroid hormone levels and short-chain PFASs concentrations.Future studies could consider a greater sample and the inclusion of other clinical indicators of thyroid function,such as free T3 and total T3.
