Association between sensitivity to thyroid hormones and non-highdensity lipoprotein cholesterol levels in patients with type 2 diabetes mellitus

BACKGROUND Dyslipidemia and type 2 diabetes mellitus(T2DM)are chronic conditions with substantial public health implications.Effective management of lipid metabolism in patients with T2DM is critical.However,there has been insufficient attention given to the relationship between thyroid hormone sensitivity and dyslipidemia in the T2DM population,particularly concerning non-high-density lipoprotein cholesterol(non-HDL-C).AIM To clarify the association between thyroid hormone sensitivity and dyslipidemia in patients with T2DM.METHODS In this cross-sectional study,thyroid hormone sensitivity indices,the thyroid feedback quantile-based index(TFQI),the thyroid-stimulating hormone index(TSHI),the thyrotrophic T4 resistance index(TT4RI),and the free triiodothyronine(FT3)/free thyroxine(FT4)ratio were calculated.Logistic regression analysis was performed to determine the associations between those composite indices and non-HDL-C levels.Random forest variable importance and Shapley Additive Explanations(SHAP)summary plots were used to identify the strength and direction of the association between hyper-non-HDL-C and its major predictor.RESULTS Among the 994 participants,389(39.13%)had high non-HDL-C levels.Logistic regression analysis revealed that the risk of hyper-non-HDL-C was positively correlated with the TFQI(OR:1.584;95%CI:1.088-2.304;P=0.016),TSHI(OR:1.238;95%CI:1.034-1.482;P=0.02),and TT4RI(OR:1.075;95%CI:1.006-1.149;P=0.032)but was not significantly correlated with the FT3/FT4 ratio.The relationships between composite indices of the thyroid system and non-HDL-C levels differed according to sex.An increased risk of hyper-non-HDL-C was associated with elevated TSHI levels in men(OR:1.331;95%CI:1.003-1.766;P=0.048)but elevated TFQI levels in women(OR:2.337;95%CI:1.4-3.901;P=0.001).Among the analyzed variables,the average SHAP values were highest for TSHI,followed by TT4RI.CONCLUSION Impaired sensitivity to thyroid hormones was associated with high non-HDL-C levels in patients with T2DM.

Association of Serum Ferritin Levels and Thyroid Hormones

Thyroid metabolism is orchestrated by the action of various minerals and trace elements including iron, iodine, selenium, and zinc. Iron deficiency, specifically deficiency in serum ferritin levels, is one of the common causes of thyroid dysfunction. Our objective was to evaluate the relationship between serum ferritin levels and circulating thyroid hormones. For this, a retrospective analysis was performed on 16,512 individuals who tested for serum levels of ferritin and thyroid profile at Vibrant America Clinical Laboratories. Subjects were stratified based on the serum levels of ferritin. Age (p −0.03232, p < 0.0001). Analysis of Linear association by Pearson’s correlation exhibited a considerable correlation between varying serum ferritin levels with all tested thyroid hormones. The study concludes that serum ferritin levels were associated with thyroid hormone synthesis and metabolism in individuals with optimal levels of circulating ferritin.

Thyroid hormones and thyroid hormone receptors: Effects of thyromimetics on reverse cholesterol transport

Reverse cholesterol transport (RCT) is a complex process which transfers cholesterol from peripheral cells to the liver for subsequent elimination from the body via feces. Thyroid hormones (THs) affect growth, develop- ment, and metabolism in almost all tissues. THs exert their actions by binding to thyroid hormone receptors (TRs). There are two major subtypes of TRs, TRα and TRβ, and several isoforms (e.g. TRα1, TRα2, TRβ1, and TRβ2). Activation of TRα1 affects heart rate, whereas activation of TRβ1 has positive effects on lipid and lipoprotein metabolism. Consequently, particular interest has been focused on the development of thyromimetic compounds targeting TRβ1, not only because of their ability to lower plasma cholesterol but also due their ability to stimulate RCT, at least in pre-clinical models. In this review we focus on THs, TRs, and on the effects of TRβ1-modulating thyromimetics on RCT in various animal models and in humans.

Stimulating effect of thyroid hormones in peripheral nerve regeneration:research history and future direction toward clinical therapy

Injury to peripheral nerves is often observed in the clinic and severe injuries may cause loss of motor and sensory functions.Despite extensive investigation,testing various surgical repair techniques and neurotrophic molecules,at present,a satisfactory method to ensuring successful recovery does not exist.For successful molecular therapy in nerve regeneration,it is essential to improve the intrinsic ability of neurons to survive and to increase the speed of axonal outgrowth.Also to induce Schwann cell phenotypical changes to prepare the local environment favorable for axonal regeneration and myelination.Therefore,any molecule that regulates gene expression of both neurons and Schwann cells could play a crucial role in peripheral nerve regeneration.Clinical and experimental studies have reported that thyroid hormones are essential for the normal development and function of the nervous system,so they could be candidates for nervous system regeneration.This review provides an overview of studies devoted to testing the effect of thyroid hormones on peripheral nerve regeneration.Also it emphasizes the importance of combining biodegradable tubes with local administration of triiodothyronine for future clinical therapy of human severe injured nerves.We highlight that the local and single administration of triiodothyronine within biodegradable nerve guide improves significantly the regeneration of severed peripheral nerves,and accelerates functional recovering.This technique provides a serious step towards future clinical application of triiodothyronine in human severe injured nerves.The possible regulatory mechanism by which triiodothyronine stimulates peripheral nerve regeneration is a rapid action on both axotomized neurons and Schwann cells.

Toxic Effects of Tetrabromobisphenol A on Thyroid Hormones in SD Rats and the Derived-reference Dose

The present study determined the thyroid hormone interference of tetrabromobisphenol A （TBBPA） in Sprague-Dawley （SD） rats, and the derived-reference dose （RfD） of different endpoint effects on mammals based on experimental results and data collection. Based on repeated exposure toxicity tests on mammals and extensive research, the present study used BMDS240 Software to derive a benchmark dose, and analyzed the accuracy and uncertainty, and similarity with other studies. Test results on triiodothyronine （T3）, thyroxine （T4）, and thyroid stimulating hormone （TSH） demonstrated that all the indicators presented a non-monotonous dose-effect relationship clearly, except TSH in male rats exposed to 0-1000 mg/kg BW per day. Therefore, RfDs were derived from different critical effects. In summary, RfD for mammals in the present study was found to be 0.6 mg/kg per day.

Comparison of Thyroid Hormones Levels in Female Ducks Blood and Embryo

[Objeclive] The comparison of levels of thyroid hormones （T3, T4 and FT3） in female ducks serum and embryo of different embryonic age between Gaoyou duck and Jinding duck were made to provide basic data for further research. [Method] The levels of thyroid hormones （T3, T4 and FT3） in female ducks serum, fertilized eggs, and 7, 11,15, 19, 22, 28-days embryo of Gaoyou duck and Jinding duck were analyzed with radioimmunoassay （RIA）. [ Result]The levels of thyroid hormones in fertilized eggs were higher than those in serum of female ducks; different em- bryonic age hormone level of Gaoyou duck and Jinding duck in serum had almost the same variation trend, which was low but relatively stable after 15 days. [Condusion] The result suggested that thyroid hormones play an important role in duck embryonic development, especially in the early peded.

Feeding Supplemental lodine to Adult Mink;Effect on Thyroid Hormones in Adult and offspring

We fed adult mink diets containing supplemental iodine, from 0 to 320 ppm, for one or seven months prior to breeding. Blood samples collected from the adults and their offspring (kits) at 4 wk post-partum were assayed for total thyroxine (T4), triiodothyronine (T3), reverse T3 (rT3), and T4-binding indices. As expected T4 concentrations of the adult and kit mink varied inversely with the level of supplemental iodine. In addition, T3 and rT3 concentrations decreased gradually in kits from the long-term experiment in response to the increased dietary iodine of the dams. T3 concentrations of kits from dams fed iodine short-term decreased markedly while rTy concentrations were elevated greatly in response to increased dietary iodine of the dam. These decreases in hormone levels are due to serum iodine blocking the thyroid uptake of iodine and subsequent decrease of hormone synthesis. Excess iodine may also block the effect of thyroid stimulating hormone. The T4-binding indices of the adults, in general, were depressed, while the T4-binding indices of the kits were more variable. These effects are probably due to fluctuations in thyroglobulin.

Characteristics of Thyroid Hormones in Hypertensive Hispanic Population

The aim was to characterize thyroid function in Hispanic hypertensive population. Retrospective study of 1,023 individuals was performed, in which 68.23% had hypertension （74.21% women） and 37.25% had thyroid pathology. Age, weight, blood pressure, biochemical measurements were recorded, mean age： 53.02 ± 14.80 yr, mean weight： 83.05 ±16.95 kg, thyrotropin-stimulating hormone （TSH） hypertensive patients： 5.55±1.63 μUI/mL and without hypertension： 3,72 ± 1.60 μUI/mL. TSH range concentration distributed by sex indicates： 1.50-2.49 μUI/mL men, 2.50-5.01 μUI/mL women. TSH categories vs. age were positively associated （r = ＋ 0.114, P = 0.044） and hypertension by age was also correlated （r = ＋ 0.178, P = 0.0001）. Significant positive association we found between TSH and diastolic blood pressure （r = ＋ 0.197, P = 0.008）. Systolic and diastolic blood pressure vs. age were positively increasing （r = ＋ 0.410,p = 0.0001; r = ＋0.285, P = 0.0001, respectively）. Prevalence of thyroid pathology in hypertensive subjects are hyperthyroidism 5.87%; hypothyroidism 20.34% （5.73% subclinic） and autoimmune disease 6.25%. High percentage of hypertensive population has concomitant thyroid diseases, more common in women （50-70 years）. Systematic surveillance for occult thyroid dysfunction in patients with hypertension could prevent future cardiovascular disease.

Serum Level of Thyroid Hormones in Patients with Chronic Hepatitis C Virus Infection

Objective: There are clinical and laboratory associations between thyroid and liver diseases. Hepatitis C virus (HCV) is known to be responsible for both hepatic and extrahepatic diseases. The most frequent and clinically important endocrine extrahepatic diseases are thyroid disorders and type 2 diabetes mellitus. We aim to study the relationship between the serum level of thyroid hormones (THs) and the severity of liver disease in patients with chronic hepatitis C virus (CHC) infection. Methods: 60 patients with CHC infection were selected for the study. They were divided into two groups: with or without liver cirrhosis. Those with liver cirrhosis were further subdivided according to the Child-Turcotte-Pugh scoring system. Serum levels of free T3 (FT3), free T4 (FT4) and TSH were measured to all patients. Results: There was decrease in the FT3 and FT4 levels and increase in the TSH levels in patients with CHC with cirrhosis when compared to patients with CHC without cirrhosis. Conclusion: Thyroid profile abnormalities were seen in cirrhotic HCV patients when compared to non-cirrhotic patients. The abnormalities in the serum level of THs (decreased FT3, FT4, and increased TSH) are strongly associated with the severity of liver damage and advancing of the child score.

Assessment of LLLT systemic effects on thyroid hormones function after dental titanium implant installation:An experimental rabbit model

This study aimed to assess the systemic effect of LLLT on thyroid gland functioning and consequently on calcium regulation through Triiodothyronine (T3) and Thyroxine (T4) measurements in rabbits’ serum. A total of thirty two New Zealand male rabbits were randomly distributed in four groups with eight animals each: control group C (nonirradiated animals), group EI (5 J/cm2 per session), group EII (10 J/cm2 per session) and group EIII (20 J/cm2 per session). All animals underwent lower left incisor extraction followed by immediate insertion of an osseintegrated implant, providing an equality of initial clinical condition between the groups. The experimental groups were irradiated with aluminium gallium arsenide diode laser (GaAlAs, λ = 830 nm, 50 mW, CW), during 13 days at each 48 hours, totalizing 7 sessions. Laboratorial T3 and T4 measurements were done in four distinct moments (before surgical procedure, immediately after surgical procedure, after the first LLLT session and after the last LLLT session) in all animals. The results obtained showed statistically significant differences in Triiodothyronine values between the groups throughout the experiment. It was concluded that the LLLT, in the protocol of irradiation used in this study, promoted a significantly alteration on rabbits’ serum hormonal levels.

Effects of PM_(2.5)and Its Components on Disease Severity in Patients with Schizophrenia and the Mediating Role of Thyroid Hormones

Studies have indicated the different effects of PM_(2.5)components on human health.However,specific components that influence the severity of disease in schizophrenia patients and their underlying mechanisms remain unclear.Therefore,a repeated measures study for schizophrenia was constructed based on Anhui Mental Health Center.We collected information,including demographics and thyroid hormones(TH)levels,on repeat admissions of schizophrenia patients during 2017−2020,assessing their illness severity by positive and negative symptom scales(PANSS).Concentrations from the nearest component monitoring station in the 3 months before admission were assigned as the participant’s exposure level.We assessed the effects of PM_(2.5)components individually and in combination on schizophrenia and explored the mediating role of THs.Results indicated that benzo[a]pyrene,sulfate,nitrate,chloride,ammonia,cadmium,chromium,lead,selenium,and thallium exposure were associated with increased PANSS scores,with more significant results observed in males.Mixed exposure to PM_(2.5)components was found to be associated with increased PANSS scores and decreased free triiodothyronine(FT3).Mediation analysis suggested that the reduction in FT3 might mediate the association between the PM_(2.5)components and PANSS scores.The findings emphasize the impacts of PM_(2.5)components on schizophrenia and the potential value of focusing on changes in THs.

Maternal Thyroid Hormones as Mediators between Phthalate Exposure and Neonatal Birth Weight:A Cross-Sectional Study from the Zunyi Birth Cohort

Studies have shown that exposure to phthalates can affect neonatal birth weight.However,epidemiological evidence on the mediating role of maternal thyroid hormones is limited.Therefore,this study,based on the Compliance Birth Cohort,aimed to reveal the potential mediating function of maternal thyroid hormones during pregnancy between phthalic acid ester(PAE)exposure and neonatal birth weight.The study included 1274 mother−infant pairs.Linear regression analysis revealed a negative association between MIBP and neonatal birth weight(β=−62.236;95%CI:−118.842,−5.631).Bayesian kernel-machine regression(BKMR)indicated a nonlinear negative association between PAE metabolites(PAEs)and birth weight.Linear regression analysis revealed a positive association between neonatal birth weight and FT3(β=41.605;95%CI:2.631,80.380).The BKMR model also found a positive association between thyroid hormones and birth weight but in a nonlinear manner.Additionally,linear regression analyses showed that TSH,TT3,TT4,FT3,and FT4 were associated with PAEs.The BKMR model revealed an inverted U-shaped association of PAEs with TT3 and FT3 and a nonlinear association with TSH,TT4,and FT4.Structural equation modeling revealed that MMP,MIBP,MBP,MEHP,MOP,MBZP,and MEOHP contributed to a net reduction in neonatal birth weight of 32 g through the TT3,FT3,TT4,and FT4 pathways.The findings suggest that exposure to PAEs during pregnancy leads to a reduction in neonatal birth weight,possibly due to the involvement of maternal thyroid hormones as mediators.Controlling maternal thyroid hormone levels during pregnancy may be a viable method to reduce the harmful effects of phthalate exposure on the developing fetus.

Human exposure to a mixture of endocrine disruptors and serum levels of thyroid hormones:A cross-sectional study

Exposure to endocrine disruptors(EDCs) could disrupt thyroid hormone homeostasis. However, human epidemiological studies reported inconsistent observations, and scarce information on the effect of a mixture of chemicals. The aim of the present study was to examine the associations of multiple chemicals with thyroid hormones among adults from China. We measured serum levels of thyroid hormones and urinary levels of 11 EDCs, including six phthalate metabolites, bisphenol A(BPA), bisphenol F(BPF), bisphenol S(BPS), perchlorate, and thiocyanate among 177 healthy adults without occupational exposure. Associations of multiple urinary analytes with serum thyroid hormones were examined by performing general linear regression analysis and bayesian kernal machine regression analysis. These EDCs were detected in almost all samples. After adjusting for various covariates, we observed only BPF significantly associated with total thyroxin(TT4)(β=-0.27, 95% confidence interval(CI) [-0.41,-0.14]), total triiodothyronine(TT3)(β=-0.02 95% CI [-0.03,-0.01]), free T4(fT4)(β=-0.02, 95% CI [-0.03,-0.01]), and free T3(fT3)(β=-0.04, 95% CI [-0.07,-0.01]), and mono-(2-ethyl-5-oxohexyl) phthalate(MEOHP) and monoethyl phthalate(MEP) positively associated with TT4(β=0.24, 95% CI [0.01, 0.48]) and fT4(β=0.02, 95% CI [0.01, 0.04]), respectively. Moreover, we observed significant dose-response relationships between TT4 and the mixture of11 EDCs, and BPF was the main contributor to the mixture effect, suggesting the priority of potential effect of BPF on disrupting thyroid function under a real scenario of human exposure to multiple EDCs. Our findings supported the hypothesis that human exposure to low levels of EDCs could alter thyroid hormones homeostasis among non-occupational healthy adults.

Association between lifestyle factors and thyroid function in young euthyroid adults

Purpose:The present work examines the associations of dietary habits,sedentarism,physical activity(PA)levels and sleep habits,with thyroid function in young euthyroid adults.Methods:A total of 105 young euthyroid adults participated in this cross-sectional study.Thyroid function was determined in fasting conditions(>6 h).Dietary habits were measured by a food frequency questionnaire and three non-consecutive 24 h recalls,and different dietary intake and patterns were then estimated.The time spent in sedentary,PA levels and sleep habits were objectively measured using a wrist-worn accelerometer.Results:Energy and carbohydrate intake were positively associated with thyroid stimulating hormone(TSH)(β=0.222;R^(2)=0.102;P=0.022 andβ=0.425;R^(2)=0.129;P=0.007,respectively)whereas fat intake was negatively associated with TSH(β=-0.428;R^(2)=0.137;P=0.004).Energy intake was also positively associated with free triiodothyronine(β=0.277;R^(2)=0.137;P=0.004).Further,adherence to the Mediterranean diet was negatively related to TSH and free thyroxine(FT4)(β=-0.221;R^(2)=0.113;P=0.020 andβ=-0.268;R^(2)=0.071;P=0.007,respectively).Vigorous-intensity and overall PA were negatively associated with FT4(β=-0.227;R^(2)=0.052;P=0.022 andβ=-0.204;R^(2)=0.042;P=0.041,respectively).In contrast,no associations were found between sleep parameters and thyroid function.Conclusions:Lifestyle factors such as dietary intake and PA levels seems to be related to thyroid function even in young euthyroid adults.

Reference Interval of Thyroidal Function of Women in the Early,Middle and Late Pregnancy in Jingzhou City,Hubei Province

[Objectives]To study the reference value of thyroid function in healthy women of childbearing age during different pregnancies(early,middle and late pregnancy)in Jingzhou City.[Methods]362 healthy women of childbearing age during different pregnancies(early,middle and late pregnancy)were selected as the study group,and 360 non-pregnant women were selected as the control group.Serum thyroid hormone levels in the two groups were detected,and the reference value was expressed as the median(M)and 95%confidence interval(CI).On this basis,the chart of changing trend of thyroid hormone in the early,middle and late pregnancy were plotted.[Results]Compared with the control group,FT3,TT4,TT3,FT4and TSH in the early,middle and late pregnancy were significantly different in the study group(P<0.05).In the study group,there were significant differences in the early,middle and late pregnancy(P<0.05).[Conclusions]This trend chart has certain reference value in the screening,diagnosis and treatment of thyroid diseases in healthy women of childbearing age during different pregnancies(early,middle and late pregnancy)in Jingzhou City of Hubei Province.

Analyses of levels of thyroid hormones and its receptor expression in puerperants and newborns from an e-waste dismantling site

In this study,the serum levels,including thyr-oid hormones free triiodothyronine(FT3),free thyroxine(FT4),thyroid stimulating hormone(TSH)among the sub-jects from the exposed group(n 548)and the control group(n 545)were detected by immuno radiometric assay(IRMA).The expression levels of TRa1,TRb1,TSHR mRNA in placentas and umbilical cords were detected by fluorescent quantitative real-time PCR(FQ-PCR).The correlations between the thyroid hormone levels in maternal serum and umbilical serum,and between the expression levels of its receptors mRNA in placentas and umbilical cords were determined.We found that the FT4 levels of both maternal serum and umbilical cord serum in the exposed group were lower than those in the control(P<0.05).However,the increased TSH levels in the exposed group had statistically significance com-pared to those in the control group(P<0.05).The TRa1 and TRb1 mRNA levels both in placentas and umbilical cords in the exposed group were lower than those in the control group(P<0.05 and 0.01).How-ever,the TSHR mRNA levels in the exposed group were significantly different compared to those in the control group(P<0.01).The serum FT4 and TSH levels of par-turient women were positively correlated with those of the newborns in both groups(P<0.05 and 0.01).The mRNA levels of TRa1,TRb1 and TSHR in the placentas were positively correlated with those in umbilical cords in both groups(P<0.01).The findings suggest that some envir-onmental pollutants existing in the electronic waste(e-waste)dismantling region may affect the health of local parturient women and newborns,representing changes both in serum levels of thyroid hormones and in mRNA expression of its receptors.

The effect of mustard seed meal(Sinapis arvensis)on thyroid hormones and liver enzymes in Japanese quails(Coturnix coturnix japonica)

Objective:To investigate the effect of wild black mustard seed meal on thyroid hormones(thyroxine and thyroid-stimulating hormone)in Japanese quails and also study the ability of FeSO4 to alleviate the possible negative effect of mustard meal on thyroid hormones in these birds for the first time.Methods:The experimental procedure was undertaken on 28 quails which were randomly assigned to a control and 6 test groups with 4 quails in each group for 28 days,during which the control group received basic diet with no mustard meal whereas the test groups(No.2,3 and 4)received mustard meal(5%,10%and 15%,respectively)and test groups(No.5,6 and 7)received FeSO_(4)(1%)-treated mustard meal(5%,10%and 15%,respectively)on the basic of basic diet.Results:The group fed on 15%non-treated mustard seed meal had the least thyroxine level and its level backed to normal in group fed on 15%FeSO4-treated mustard seed meal although this group had the highest alanine transaminase and aspartate transaminase levels.Conclusions:We concluded that up to 10%FeSO4 mustard seed meal could be incorporated in the quail diet successfully with the least damage to thyroids and livers,but further investigations on these birds are still needed to confirm this hypothesis.

The effects and mechanisms of thyroid hormones in the cardiovascular system

Background Thyroid hormones(THs) including thyroxine(T4) and triiodothyronine(T3) with high biological activities have important effects on cardiovascular system by acting on renin-angiotensin-aldosterone system(RAAS), oxidative stress, mitochondria, endothelial cells, vascular smooth muscle cells(VSMC), cardiomyocytes, thyroid hormone receptor(TRs), cholesterol metabolism, insulin sensitivity, blood coagulation, etc. Excess or lack of THs is detrimental to cardiovascular function, so this article reviews the mechanism of THs on cardiovascular system.[S Chin J Cardiol 2019;20(4):269-279]

Effect of Ginseng Injection on Congestive Heart Failure and Thyroid Hormones

Objective: To observe the effect of Ginseng injection on congestive heart failure (CHF) and its influence on thyroid hormones.Methods: Fifty-four patients of CHF were divided into two groups. On the basis of conventional treatment of western medicine, the Ginseng injection was given to the treated group additionally. Blood level of triiodothyronine (T3), thyroxine (T4), reverse triiodothyronine (rT3) and thyroid stimulating hormone of all patients were determined before and after treatment by radioimmunoassay.Results: There were significant difference between the treated group and the control group in cure rate and mean course of therapy. The levels of T3 and T4 of all patients were lower than those of the normal control before treatment, and rT3 were higher. Two weeks after treatment, T3 and T4 level in all patients increased significantly and rT3 level significantly decreased (P < 0.05,P < 0.01).Conclusion: Ginseng injection has a good effect on patients with CHF. It also has regulatory effect on thyroid hormones.

Hypomethylation of Thyroid Peroxidase as a Biomarker for Hepatocellular Carcinoma with Tumor Thrombosis

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.