Publications by authors named "Bingyin Shi"

141 Publications

Hyperthyroidism Prevalence in China After Universal Salt Iodization.

Front Endocrinol (Lausanne) 2021 28;12:651534. Epub 2021 May 28.

Zhejiang Center for Disease Control and Prevention (Zhejiang CDC), Hangzhou, China.

Background: Universal salt iodization (USI) was implemented in mainland China in 1996. The prevalence of hyperthyroidism and its risk factors now require examination.

Methods: Data were acquired from a nationwide Thyroid, Iodine, and Diabetes Epidemiological survey (TIDE 2015-2017) of 78,470 subjects from 31 provinces. Iodine status, and thyroid hormones and antibodies were measured.

Results: After two decades of USI, the prevalence of overt hyperthyroidism (OH), Graves' disease (GD), severe subclinical hyperthyroidism (severe SCH), and mild subclinical hyperthyroidism (mild SCH) in mainland China was 0.78%, 0.53%, 0.22%, and 0.22%, respectively. OH and GD prevalence were higher in women than in men (OH: 1.16% . 0.64%, P<0.001; GD: 0.65% . 0.37%, P<0.001).Prevalence was significantly decreased after 60 years-of-age compared with 30-39 years-of-age (OH:0.61% . 0.81%, P<0.001; GD: 0.38% . 0.57%, P<0.001).Excessive iodine(EI) and deficient iodine(DI) were both related to increased prevalence of OH (odds ratio [OR] 2.09, 95% confidence interval [CI] 1.68-2.59; OR1.35, 95%CI 1.07-1.72, respectively); however, only deficient iodine was associated with increased prevalence of GD (OR1.67, 95%CI 1.30-2.15). Increased thyroid peroxidase antibody and thyroglobulin antibody levels were significantly associated with prevalence of OH and GD, but not severe SCH and mild SCH. Although hyperthyroidism was more prevalent in women, the association disappeared after adjusting for other factors such as antibody levels.

Conclusion: OH and GD prevalences in mainland China are stable after two decades of USI. Iodine deficiency, elevated thyroid antibody levels, and middle age are the main risk factors for OH and GD. The severe SCH population, rather than the mild SCH population, shows similar characteristics to the OH population.
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http://dx.doi.org/10.3389/fendo.2021.651534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194401PMC
May 2021

Leptin receptor is a key gene involved in the immunopathogenesis of thyroid-associated ophthalmopathy.

J Cell Mol Med 2021 Jun 14;25(12):5799-5810. Epub 2021 May 14.

Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Thyroid-associated ophthalmopathy (TAO), the most common and severe manifestation of Graves' disease (GD), is a disfiguring and potentially blinding autoimmune disease. The high relapse rate (up to 20%) and substantial side effects of glucocorticoid treatment further decrease the life quality of TAO patients. To develop novel therapies, we amid to explore the immunopathogenesis of TAO. To identify the key immune-related genes (IRGs) in TAO, we integrated the IRG expression profiles in thyrocytes from a GD patient set (GD vs healthy control) and a TAO patient set (TAO vs GD). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction (PPI) and receiver operating characteristic (ROC) curve analyses identified the leptin receptor (LEPR) gene as the key IRG in TAO immunopathogenesis. Gene set enrichment analysis (GSEA) suggested enrichment of the antigen presentation pathway in TAO patients with higher LEPR. Increased LEPR expression was validated in TAO orbital tissues, and weighted gene co-expression network analysis (WGCNA) showed that cell adhesion processes were positively correlated with LEPR. Our study revealed that LEPR is a key gene in TAO immunopathogenesis and plays different roles in thyrocytes and orbital tissues. Our findings provide new insights into diagnostic and therapeutic biomarkers for TAO.
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http://dx.doi.org/10.1111/jcmm.16605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184729PMC
June 2021

Decreased Treg Cell and TCR Expansion Are Involved in Long-Lasting Graves' Disease.

Front Endocrinol (Lausanne) 2021 12;12:632492. Epub 2021 Apr 12.

Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Graves' disease (GD) is a T cell-mediated organ-specific autoimmune disorder. GD patients who have taken anti-thyroid drugs (ATDs) for more than 5 years with positive anti-thyroid stimulating hormone receptor autoantibodies value were defined as persistent GD (pGD). To develop novel immunotherapies for pGD, we investigated the role of T cells in the long-lasting phase of GD. Clinical characteristics were compared between the pGD and newly diagnosed GD (nGD) (N = 20 respectively). Flow cytometric analysis was utilized to determine the proportions of Treg and Th17 cells (pGD, N = 12; nGD, N = 14). T cell receptor sequencing (TCR-seq) and RNA sequencing (RNA-seq) were also performed (pGD, N = 13; nGD, N = 20). Flow cytometric analysis identified lower proportions of Th17 and Treg cells in pGD than in nGD (P = 0.0306 and P = 0.0223). TCR-seq analysis revealed a lower diversity (P = 0.0025) in pGD. Specifically, marked clonal expansion, represented by an increased percentage of top V-J recombination, was observed in pGD patients. Interestingly, pGD patients showed more public T cell clonotypes than nGD patients (2,741 966). Meanwhile, RNA-seq analysis revealed upregulation of the inflammation and chemotaxis pathways in pGD. Specifically, the expression of pro-inflammatory and chemotactic genes (, , , and ) was increased in pGD, whereas Th17 and Treg cells associated genes (, , , and decreased in pGD. Additionally, TCR diversity was negatively correlated with the expression of pro-inflammatory or chemotactic genes (, , , and ). These results indicated that Treg dysregulation and the expansion of pathogenic T cell clones might be involved in the long-lasting phase of GD upregulating chemotaxis or inflammation response. To improve the treatment of pGD patients, ATDs combined therapies, especially those aimed at improving Treg cell frequencies or targeting specific expanded pathogenic TCR clones, are worth exploring in the future.
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http://dx.doi.org/10.3389/fendo.2021.632492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074859PMC
April 2021

Efficacy and tolerability of sitagliptin and metformin compared with insulin as an initial therapy for newly diagnosed diabetic patients with severe hyperglycaemia.

Exp Ther Med 2021 Mar 15;21(3):217. Epub 2021 Jan 15.

Department of Endocrinology and International Medical Center, The First Affiliated Hospital of Xi'an JiaoTong University, Xi'an, Shaanxi 710061, P.R. China.

The safety and efficacy of dipeptidyl peptidase-4 inhibitors in patients newly diagnosed type 2 diabetes mellitus (T2DM) with severe hyperglycaemia have remained to be sufficiently demonstrated. The aim of the present study was to determine whether sitagliptin combined with metformin as an initial treatment had non-inferior outcomes with regards to glycaemic remission and β-cell function recovery to those of standard insulin therapy in this patient group. A prospective observational study was performed comparing the effects of sitagliptin combined with metformin and insulin therapy in a real-world clinical setting. A total of 168 participants were enrolled and received sitagliptin combined with metformin (Sig) or insulin (Ins) for almost 4 weeks. In addition, each group was further stratified into three subgroups, according to glycosylated haemoglobin (HbA1c) levels (<10, 10-12 and >12%). The primary outcomes were β-cell function and changes in fasting plasma glucose (FPG) and HbA1c at the 3-month follow-up. Both insulin and sitagliptin combined with metformin reduced hyperglycaemia and achieved similar glycaemic outcomes, and no significant differences in FPG and HbA1c levels were obtained. No significant changes were observed in β-cell function concomitant with the glucose-lowering effects of the treatments. Of note, participants in the Ins group exhibited weight gain, whereas those in the Sig group had weight loss, with significant differences becoming evident after 1 month, particularly in the HbA1c <10% subgroup. As compared with insulin injection, early treatment with sitagliptin combined with metformin in newly diagnosed patients with T2DM and severe hyperglycaemia produced non-inferior outcomes with regards to glycaemic remission. Therefore, combination of sitagliptin and metformin may be a viable initial treatment option for patients who prefer an alternative to insulin injection. This study was registered with ClinicalTrials.gov under no. NCT03180281.
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http://dx.doi.org/10.3892/etm.2021.9649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818522PMC
March 2021

A novel CD4+ CTL subtype characterized by chemotaxis and inflammation is involved in the pathogenesis of Graves' orbitopathy.

Cell Mol Immunol 2021 Mar 29;18(3):735-745. Epub 2021 Jan 29.

Department of Endocrinology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Graves' orbitopathy (GO), the most severe manifestation of Graves' hyperthyroidism (GH), is an autoimmune-mediated inflammatory disorder, and treatments often exhibit a low efficacy. CD4+ T cells have been reported to play vital roles in GO progression. To explore the pathogenic CD4+ T cell types that drive GO progression, we applied single-cell RNA sequencing (scRNA-Seq), T cell receptor sequencing (TCR-Seq), flow cytometry, immunofluorescence and mixed lymphocyte reaction (MLR) assays to evaluate CD4+ T cells from GO and GH patients. scRNA-Seq revealed the novel GO-specific cell type CD4+ cytotoxic T lymphocytes (CTLs), which are characterized by chemotactic and inflammatory features. The clonal expansion of this CD4+ CTL population, as demonstrated by TCR-Seq, along with their strong cytotoxic response to autoantigens, localization in orbital sites, and potential relationship with disease relapse provide strong evidence for the pathogenic roles of GZMB and IFN-γ-secreting CD4+ CTLs in GO. Therefore, cytotoxic pathways may become potential therapeutic targets for GO.
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http://dx.doi.org/10.1038/s41423-020-00615-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027210PMC
March 2021

Combined treatment with a gastric inhibitory polypeptide receptor antagonist and a peptidyl peptidase-4 inhibitor improves metabolic abnormalities in diabetic mice.

J Int Med Res 2021 Jan;49(1):300060520985664

Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an Shaanxi Province, China.

Objectives: Dipeptidyl peptidase-4 inhibition and gastric inhibitory polypeptide (GIP) receptor antagonism have therapeutic effects in type 2 diabetes mellitus. We assessed the effects of sitagliptin and Pro(GIP) in a mouse model of diabetes.

Methods: Diabetes was induced in C57BL/6J mice by a high-fat diet and intraperitoneal injection of streptozocin. Blood glucose was assessed weekly. Six weeks later, serum triglycerides, total cholesterol and glucose tolerance were assessed and pancreatic and adipose tissues were collected.

Results: Combination therapy with sitagliptin and Pro(GIP) resulted in significantly greater reductions of blood glucose and triglycerides than either monotherapy. Combination therapy also improved insulin sensitivity and glucose tolerance. β-cell mass and insulin-positive cell percentage in the pancreas was higher in mice receiving combination therapy compared with either monotherapy. Crown-like structures, inflammatory markers in adipose tissue, and serum leptin concentrations were decreased in mice receiving combination therapy compared with either monotherapy.

Conclusions: Combination therapy with Pro(GIP) and sitagliptin improved metabolic abnormalities in diabetic mice. Changes in serum leptins and reduced inflammatory cell infiltration in adipose tissue might account for the observed effects.
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http://dx.doi.org/10.1177/0300060520985664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871083PMC
January 2021

The Correlation Between Metabolic Disorders And Tpoab/Tgab: A Cross-Sectional Population-Based Study.

Endocr Pract 2020 Aug;26(8):869-882

Department of Endocrinology and Metabolism, Affiliated Hospital of Guiyang Medical University, Guiyang, Guizhou, P.R. China.

Objective: Studies have shown that metabolic abnormalities influence the immune system. Because the prevalence of metabolic and autoimmune thyroid diseases has increased synchronously, the correlation between them was worth exploring. The study objective was to investigate the relationship between metabolic disorders and thyroid auto-antibodies in euthyroid subjects.

Methods: Data were obtained from the Thyroid Diseases and Diabetes Mellitus project survey of 55,891 subjects from 31 provinces in China. The body mass index (BMI), waist circumference (WC), blood pressure, thyroid peroxidase antibodies (TPOAbs), thyroglobulin antibodies (TgAbs), thyroid-stimulating hormone (TSH), urinary iodine concentration, blood glucose, lipid profile, and uric acid levels were evaluated. Free thyroxine and free triiodothyronine levels were measured in patients with abnormal serum TSH levels.

Results: In males, the BMI, WC, systolic blood pressure (SBP), diastolic blood pressure (DBP), and 2-hour post-glucose oral glucose tolerance test results of the TPOAb-/TgAb-positive group were significantly higher than those of the TPOAb-/TgAb-negative group. In females, the BMI, WC, SBP, DBP, total cholesterol, and low-density-lipoprotein cholesterol (LDL-C) in the TPOAb-/TgAb-positive group were significantly increased compared to the TPOAb-/TgAb-negative group. Multivariate analysis showed that in males, the odds ratio (OR) of positive TgAbs in the abdominal obesity group was 1.175 (95% confidence interval [CI], 1.016 to 1.359; P = .03), and the OR of positive TPOAbs in the hyperuricemia group was 1.195 (95% CI, 1.041 to 1.372; P = .011). In females, the OR of positive TgAbs was 1.19 (95% CI, 1.068 to 1.326; P = .002) in the high LDL-C group.

Conclusion: Obesity, high LDL-C, and hyperuricemia were positively correlated with the prevalence of positive thyroid autoantibodies in euthyroid subjects in a gender-dependent manner. This cross-sectional survey showed that metabolic disorders are associated with increased positive thyroid autoantibody levels in euthyroid subjects in a gender-dependent manner.

Abbreviations: AIT = autoimmune thyroiditis; BMI = body mass index; CI = confidence interval; DBP = diastolic blood pressure; FPG = fasting plasma glucose; FT3 = free triiodothyronine; FT4 = free thyroxine; HbA1c = glycated hemoglobin; HDL-C = high-density-lipoprotein cholesterol; LDL-C = low-density-lipoprotein cholesterol; OGTT2hPG = oral glucose tolerance test 2-hours post-glucose; OR = odds ratio; SBP = systolic blood pressure; TC = total cholesterol; TG = triglycerides; TgAb = thyroglobulin antibody; TPOAb = thyroid peroxidase antibody; TSH = thyroid-stimulating hormone; UA = uric acid; WC = waist circumference.
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http://dx.doi.org/10.4158/EP-2020-0008DOI Listing
August 2020

Association between Urinary Iodine Concentration and Thyroid Nodules in Adults: A Cross-Sectional Study in China.

Biomed Res Int 2020 17;2020:4138657. Epub 2020 Dec 17.

Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Background: Associations between iodine intake and thyroid nodules (TNs) were not consistent. We aimed to illustrate the relationship between urinary iodine concentration (UIC) and TNs.

Methods: A total of 12,698 participants were enrolled in analysis. All of the participants filled out questionnaires and underwent physical examinations, laboratory tests, and thyroid ultrasonography. UIC, serum thyrotropin (TSH), thyroid peroxidase antibodies (TPOAb), and thyroglobulin antibodies (TgAb) were measured in the central laboratory.

Results: The prevalence of TNs was 16.00%, and the median UIC was 206.1 g/L. TNs and UIC were negatively related when UIC was less than 527 g/L (adjusted OR = 0.87; 95% CI, 0.80, 0.94), and the relationship between UIC and TNs was not statistically significant when UIC was greater than 527 g/L (adjusted OR = 1.25; 95% CI, 0.98, 1.60). In women, UIC was negatively associated with risk for TNs (adjusted OR 0.95; 95% CI, 0.91, 0.99).

Conclusion: The relationship between TNs and UIC differed between men and women. The risk of TNs decreased with the elevation of UIC in men when UIC was lower than 527 g/L, while UIC and the presence of TNs were negatively correlated in women. In the future, cohort studies or other studies that can explain causality must be conducted to explore the relationship between iodine status and TNs.
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http://dx.doi.org/10.1155/2020/4138657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762642PMC
May 2021

Mitochondrial Fission and Mitophagy Coordinately Restrict High Glucose Toxicity in Cardiomyocytes.

Front Physiol 2020 10;11:604069. Epub 2020 Dec 10.

Department of Biomedical Sciences, New York Institute of Technology, College of Osteopathic Medicine, Old Westbury, NY, United States.

Hyperglycemia-induced mitochondrial dysfunction plays a key role in the pathogenesis of diabetic cardiomyopathy. Injured mitochondrial segments are separated by mitochondrial fission and eliminated by autophagic sequestration and subsequent degradation in the lysosome, a process termed mitophagy. However, it remains poorly understood how high glucose affects the activities of, and the relationship between, mitochondrial fission and mitophagy in cardiomyocytes. In this study, we determined the functional roles of mitochondrial fission and mitophagy in hyperglycemia-induced cardiomyocyte injury. High glucose (30 mM, HG) reduced mitochondrial connectivity and particle size and increased mitochondrial number in neonatal rat ventricular cardiomyocytes, suggesting an enhanced mitochondrial fragmentation. SiRNA knockdown of the pro-fission factor dynamin-related protein 1 (DRP1) restored mitochondrial size but did not affect HG toxicity, and Mdivi-1, a DRP1 inhibitor, even increased HG-induced cardiomyocyte injury, as shown by superoxide production, mitochondrial membrane potential and cell death. However, DRP1 overexpression triggered mitochondrial fragmentation and mitigated HG-induced cardiomyocyte injury, suggesting that the increased mitochondrial fission is beneficial, rather than detrimental, to cardiomyocytes cultured under HG conditions. This is in contrast to the prevailing hypothesis that mitochondrial fragmentation mediates or contributes to HG cardiotoxicity. Meanwhile, HG reduced mitophagy flux as determined by the difference in the levels of mitochondria-associated LC3-II or the numbers of mitophagy foci indicated by the novel dual fluorescent reporter mt-Rosella in the absence and presence of the lysosomal inhibitors. The ability of HG to induce mitochondrial fragmentation and inhibit mitophagy was reproduced in adult mouse cardiomyocytes. Overexpression of Parkin, a positive regulator of mitophagy, or treatment with CCCP, a mitochondrial uncoupler, induced mitophagy and attenuated HG-induced cardiomyocyte death, while Parkin knockdown had opposite effects, suggesting an essential role of mitophagy in cardiomyocyte survival under HG conditions. Strikingly, Parkin overexpression increased mitochondrial fragmentation, while DRP1 overexpression accelerated mitophagy flux, demonstrating a reciprocal activation loop that controls mitochondrial fission and mitophagy. Thus, strategies that promote the mutual positive interaction between mitochondrial fission and mitophagy while simultaneously maintain their levels within the physiological range would be expected to improve mitochondrial health, alleviating hyperglycemic cardiotoxicity.
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http://dx.doi.org/10.3389/fphys.2020.604069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758327PMC
December 2020

Exposure to the Chinese Great Famine in Early Life and Thyroid Function and Disorders in Adulthood: A Cross-Sectional Study.

Thyroid 2021 04 23;31(4):563-571. Epub 2020 Dec 23.

Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, P.R. China.

Malnutrition in early life may permanently change the structure and function of the body, which lead to a number of diseases in adulthood. The effect of famine exposure during the early life on thyroid function and disorders remains unclear. This study investigated the association between exposure to the Great Chinese Famine (1959-1961) in early life and thyroid function and disorders in adulthood. Nine thousand eight hundred eighty-one subjects with appropriate birth dates derived from the Thyroid disorders, Iodine status, and Diabetes Epidemiological survey were included. Thyroid function and disorders were defined by the test results of blood sample and ultrasonography of all participants. Associations between famine exposure in early life and thyroid function and disorders in adulthood were assessed with binary logistic regression and linear regression. Participants exposed to the Great Chinese Famine during the fetal stage was associated with a higher thyrotropin (TSH) level in adulthood ( = 0.024;  = 0.038), compared with the nonexposed participants. The association was significant among rural participants ( = 0.039;  = 0.02) but not in urban participants ( = 0.005;  = 0.77). Fetal-exposed group did not show a higher risk of thyroid disorders than the age-matched balanced control group, including overt hyperthyroidism, subclinical hyperthyroidism, overt hypothyroidism, subclinical hypothyroidism, autoimmune thyroiditis, and thyroid nodules ( > 0.05). Famine exposure during the fetal stage was associated with a higher TSH level in adulthood. The fetal stage could be the critical period for programming the pituitary-thyroid axis.
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http://dx.doi.org/10.1089/thy.2020.0325DOI Listing
April 2021

A Role of Endogenous Histone Acetyltransferase Steroid Hormone Receptor Coactivator 3 in Thyroid Hormone Signaling During Intestinal Metamorphosis.

Thyroid 2021 04 20;31(4):692-702. Epub 2020 Nov 20.

Section on Molecular Morphogenesis, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland, USA.

Thyroid hormone (triiodothyronine [T3]) plays an important role in regulating vertebrate developmental, cellular, and metabolic processes via T3 receptor (TR). Liganded TR recruit coactivator complexes that include steroid receptor coactivators (SRC1, SRC2 or SRC3), which are histone acetyltransferases, to T3-responsive promoters. The functions of endogenous coactivators during T3-dependent mammalian adult organ development remain largely unclear, in part, due to the difficulty to access and manipulate late-stage embryos and neonates. We use metamorphosis as a model for postembryonic development in vertebrates. This process is controlled by T3, involves drastic changes in every organ/tissue, and can be easily manipulated. We have previously found that SRC3 was upregulated in the intestine during amphibian metamorphosis. To determine the function of endogenous SRC3 during intestinal remodeling, we have generated animals lacking a functional SRC3 gene and analyzed the resulting phenotype. Although removing SRC3 had no apparent effect on external development and animal gross morphology, the SRC3 (-/-) tadpoles displayed a reduction in the acetylation of histone H4 in the intestine compared with that in wild-type animals. Further, the expression of TR target genes was also reduced in SRC3 (-/-) tadpoles during intestinal remodeling. Importantly, SRC3 (-/-) tadpoles had inhibited/delayed intestinal remodeling during natural and T3-induced metamorphosis, including reduced adult intestinal stem cell proliferation and apoptosis of larval epithelial cells. Our results, thus, demonstrate that SRC3 is a critical component of the TR-signaling pathway during intestinal remodeling.
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http://dx.doi.org/10.1089/thy.2020.0410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195878PMC
April 2021

Selenium deficiency is linearly associated with hypoglycemia in healthy adults.

Redox Biol 2020 10 1;37:101709. Epub 2020 Sep 1.

Institute for Experimental Endocrinology, Charité-Universitätsmedizin Berlin, CVK, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, And Berlin Institute of Health, 13353, Berlin, Germany. Electronic address:

Objective: The trace element selenium (Se) is needed for regular biosynthesis of selenoproteins, which contribute to antioxidative defense systems and affect redox-regulated signaling. Elevated Se intake and selenoprotein expression levels have been associated with impaired hydrogen peroxide-dependent signaling by insulin, leading to hyperglycemia and insulin resistance. The relation of low Se intake with glucose status and carbohydrate metabolism is poorly known.

Research Design And Methods: A cross sectional analysis among healthy subjects residing in two Chinese counties with different habitual Se intakes was conducted. Fasted glucose levels were related to Se concentrations of 5686 adults by linear regression analysis with Se, body mass index, age, thyroid status, insulin and sex as independent variables.

Results: Serum Se correlated strongly and positively with glucose in the Se-deficient population. There was no strong relationship of Se and glucose in the non-deficient population. Overt hypoglycemia (serum glucose < 2.8 mM) was observed in 19.2% of this random sample of subjects in the Se-deficient and in 1.4% of the moderately supplied population, respectively.

Conclusions: An adequate Se supply constitutes an important factor for glucose homeostasis in human subjects. The interaction between Se status and glucose control is not limited to hyperglycemia, but apparently extends to hypoglycemia risk in Se deficiency. This newly identified relationship may be of relevance for the course of severe disease including major trauma, sepsis and COVID-19, where Se deficiency has been associated with mortality risk.
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http://dx.doi.org/10.1016/j.redox.2020.101709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462470PMC
October 2020

The Effect of Increased Iodine Intake on Serum Thyrotropin: A Cross-Sectional, Chinese Nationwide Study.

Thyroid 2020 12 21;30(12):1810-1819. Epub 2020 Sep 21.

Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, P.R. China.

Subclinical hypothyroidism is diagnosed based on serum thyrotropin (TSH) reference intervals, which in turn are affected by many factors. Data were acquired from a Chinese nationally representative cross-sectional study of 78,470 participants (TIDE study). The total study population were participants from the TIDE program, and the reference population was a subset of the total population defined by the National Academy of Clinical Biochemistry (NACB) guidelines. Serum concentrations of thyroid hormones, TSH, thyroid antibodies, and urine iodine concentration (UIC) were measured. The geometric mean serum TSH (2.5th-97.5th) for the reference population (defined by the NACB) and total population was 2.28 mIU/L (0.74-7.04 mIU/L) and 2.34 mIU/L (0.61-8.33 mIU/L), respectively. In the reference population, increase in UIC was significantly associated with increase in the 50th and 97.5th centiles and decrease in the 2.5th centile of TSH. The median TSH was significantly higher in women than in men (2.41 mIU/L vs. 2.16 mIU/L, -value <0.001). Increased age was significantly associated with an increased TSH, 97.5th centile. For each 10-year increase in the population age, the TSH 97.5th centile increased by 0.534 mIU/L. The prevalence of subclinical hypothyroidism diagnosed according to the assay-recommended interval (Roche 0.27-4.2 mIU/L) and NACB standard interval in the TIDE study (0.74-7.04 mIU/L) differed significantly (Roche 13.61% vs. TIDE 3.00%,  < 0.05). However, there was no significant difference in future cardiovascular disease, reflected by the Framingham risk score, between the 0.27-4.2 and 4.2-7.04 mIU/L TSH groups. Serum TSH concentration significantly increased with increase in iodine intake. Thus, iodine intake must be considered in establishing TSH reference intervals. To avoid overdiagnosis and overtreatment of subclinical hypothyroidism, different areas should use individual serum TSH reference intervals.
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http://dx.doi.org/10.1089/thy.2019.0842DOI Listing
December 2020

An Inverse Relationship Between Iodine Intake and Thyroid Antibodies: A National Cross-Sectional Survey in Mainland China.

Thyroid 2020 11 23;30(11):1656-1665. Epub 2020 Jul 23.

Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, P.R. China.

Iodine intake is associated with thyroid autoimmunity. In this study, we evaluated the changes in thyroid autoimmunity after 20 years of universal salt iodization (USI) in China. A total of 78,470 subjects (18 years or older) from 31 provincial regions of mainland China participated in the study. Serum thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), TSH receptor antibody, thyrotropin (TSH), and urinary iodine concentration (UIC) were measured. Positive TPOAb and TgAb were detected in 10.19% [CI 9.80-10.59] and 9.70% [CI 9.28-10.13] of the subjects, respectively. The prevalence of positive isolated TPOAb (i-TPOAb), positive isolated TgAb (i-TgAb), and double positive TPOAb and TgAb (d-Ab) was 4.52%, 4.16%, and 5.94%, respectively. The prevalence of thyroid antibody positivity was the highest in the iodine-deficient (UIC <100 μg/L) groups. The prevalence of i-TPOAb was inversely associated with more than adequate iodine intake (MAI) and excessive iodine intake (EI); the odds ratio (OR) was 0.89 [CI 0.81-0.98] for MAI and 0.90 [CI 0.81-0.99] for EI. We observed that i-TgAb, like i-TPOAb, was a high-risk factor for subnormal TSH levels (OR = 3.64 [CI 2.62-5.05]) and elevated TSH levels (OR = 1.62 [CI 1.49-1.77]). The prevalence of thyroid antibody positivity varied among five ethnic groups. After two decades of USI, the prevalence of thyroid antibody positivity has remained low. MAI and EI had an inverse relationship with TPOAb positivity, which reveals that UIC between 100 and 299 μg/L is optimal and safe for thyroid autoimmunity. These conclusions need to be confirmed in a follow-up study because this study was a cross-sectional study.
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http://dx.doi.org/10.1089/thy.2020.0037DOI Listing
November 2020

Intestinal homeostasis: a communication between life and death.

Cell Biosci 2020 19;10:66. Epub 2020 May 19.

2Section on Molecular Morphogenesis, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, MD 20892 USA.

Organ homeostasis is essential for organ physiology and disease prevention. In adult vertebrates, the intestinal epithelium is maintained through constant cell proliferation in the crypt and apoptosis of differentiated epithelial cells, mainly at the tip of the villus. Based on studies with altered cell proliferation and tissue damage in the adult mouse intestine, we hypothesize that there is a communication between cell proliferation in the crypt and cell death on the villus, likely via cell-cell and cell-ECM (extracellular matrix) interactions, to coordinate the rate of cell proliferation and death, thus ensuring epithelial homeostasis.
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http://dx.doi.org/10.1186/s13578-020-00429-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236522PMC
May 2020

Prevalence of diabetes recorded in mainland China using 2018 diagnostic criteria from the American Diabetes Association: national cross sectional study.

BMJ 2020 04 28;369:m997. Epub 2020 Apr 28.

Department of Endocrinology and Metabolism, Affiliated Hospital of Guiyang Medical University, Guiyang, Guizhou, China.

Objective: To assess the prevalence of diabetes and its risk factors.

Design: Population based, cross sectional study.

Setting: 31 provinces in mainland China with nationally representative cross sectional data from 2015 to 2017.

Participants: 75 880 participants aged 18 and older-a nationally representative sample of the mainland Chinese population.

Main Outcome Measures: Prevalence of diabetes among adults living in China, and the prevalence by sex, regions, and ethnic groups, estimated by the 2018 American Diabetes Association (ADA) and the World Health Organization diagnostic criteria. Demographic characteristics, lifestyle, and history of disease were recorded by participants on a questionnaire. Anthropometric and clinical assessments were made of serum concentrations of fasting plasma glucose (one measurement), two hour plasma glucose, and glycated haemoglobin (HbA).

Results: The weighted prevalence of total diabetes (n=9772), self-reported diabetes (n=4464), newly diagnosed diabetes (n=5308), and prediabetes (n=27 230) diagnosed by the ADA criteria were 12.8% (95% confidence interval 12.0% to 13.6%), 6.0% (5.4% to 6.7%), 6.8% (6.1% to 7.4%), and 35.2% (33.5% to 37.0%), respectively, among adults living in China. The weighted prevalence of total diabetes was higher among adults aged 50 and older and among men. The prevalence of total diabetes in 31 provinces ranged from 6.2% in Guizhou to 19.9% in Inner Mongolia. Han ethnicity had the highest prevalence of diabetes (12.8%) and Hui ethnicity had the lowest (6.3%) among five investigated ethnicities. The weighted prevalence of total diabetes (n=8385) using the WHO criteria was 11.2% (95% confidence interval 10.5% to 11.9%).

Conclusion: The prevalence of diabetes has increased slightly from 2007 to 2017 among adults living in China. The findings indicate that diabetes is an important public health problem in China.
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http://dx.doi.org/10.1136/bmj.m997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186854PMC
April 2020

THE CORRELATION BETWEEN METABOLIC DISORDERS AND TPOAB/TGAB: A CROSS-SECTIONAL POPULATION-BASED STUDY.

Endocr Pract 2020 Apr 27. Epub 2020 Apr 27.

Department of Endocrinology and Metabolism, Affiliated Hospital of Guiyang Medical University, Guiyang, Guizhou, P.R. China, 550004.

Objectives: Studies have shown that metabolic abnormalities influence the immune system. Because the prevalence of metabolic and autoimmune thyroid diseases has increased synchronously, the correlation between them was worth exploring. The study objective was to investigate the relationship between metabolic disorders and thyroid autoantibodies in euthyroid subjects.

Methods: Data were obtained from a TIDE project survey of 55,891 subjects from 31 provinces in China. The body mass index(BMI), waist circumference(WC), blood pressure(BP), TPOAb, TgAb, TSH, UIC, blood glucose, lipid profile, uric acid(UA) levels were evaluated. FT4 and FT3 levels were measured in patients with abnormal serum TSH levels.

Results: In males, the BMI, WC, SBP, DBP, and OGTT2hPG of the TPOAb/TgAb-positive groups were significantly higher than those of the TPOAb/TgAb-negative groups. In females, the BMI, WC, SBP, DBP, TC, and LDL-C in the TPOAb/TgAb-positive groups were significantly increased compared to those in the TPOAb/TgAb-negative groups. Multivariate analysis showed that, in males, the OR of positive TgAb in the abdominal obesity group was 1.175 (95% CI 1.016-1.359, P for difference= 0.03), and the OR of positive TPOAb in the hyperuricemia group was 1.195 (95% CI 1.041-1.372, P for difference = 0.011). In females, the OR of positive TgAb was 1.19 (95% Cl 1.068-1.326, P for difference= 0.002) in the high LDL-C group.

Conclusions: Obesity, high LDL-C and hyperuricemia were positively correlated with the prevalence of positive thyroid autoantibodies in euthyroid subjects in a gender-dependent manner. This cross-sectional survey showed that metabolic disorders are associated with increased positive thyroid autoantibody levels in euthyroid subjects in a gender-dependent manner.
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http://dx.doi.org/10.4158/EP-2020-0008DOI Listing
April 2020

Diagnostic significance of DNA methylation of PTEN and DAPK in thyroid tumors.

Clin Endocrinol (Oxf) 2020 08 2;93(2):187-195. Epub 2020 Jun 2.

Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University Health Science Center, Xi'an, China.

Objective: DNA Methylation of the tumour suppressor gene leading to gene silencing plays an important role in thyroid tumour development. The purpose was to determine the DNA methylation status of phosphatase and tensin homolog (PTEN) and death-associated protein kinase (DAPK) in patients with thyroid nodules and to explore whether they can be used as molecular diagnostic tools to differentiate benign and malignant thyroid nodules.

Design, Patients And Measurements: Thyroid tissue and blood samples were obtained from normal healthy individuals (controls) and patients suffering from clinically diagnosed thyroid nodular disease [papillary thyroid carcinoma (PTC), adenoma and nodular goitre]. DNA methylation level, mRNA expression and protein expression of PTEN and DAPK in the thyroid tissues and peripheral blood were detected using methylation-specific PCR, semi-quantitative reverse transcription PCR and Western blot, respectively. Diagnostic sensitivity, specific and accuracy of detection were evaluated between blood and thyroid tissue.

Results: There was a significant increase in the level of DNA methylation of PTEN and DAPK in PTC (P < .05) compared with controls and other types of thyroid nodules. Levels of the mRNA of both PTEN and DAPK were lower in PTC in both peripheral blood and tissue samples compared with controls, while there was concomitant decrease of both PTEN and DAPK protein expression in PTC tissues (P < .05). There was no significant difference in diagnostic specificity, sensitivity and accuracy between blood sample and thyroid tissues.

Conclusions: Hypermethylated status of both PTEN and DAPK in peripheral blood and tissue samples can be useful biomarkers for clinical diagnosis and, distinguishing of benign and malignant thyroid nodules.
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http://dx.doi.org/10.1111/cen.14192DOI Listing
August 2020

The Presence of Serum TgAb Suggests Lower Risks for Glucose and Lipid Metabolic Disorders in Euthyroid General Population From a National Survey.

Front Endocrinol (Lausanne) 2020 18;11:139. Epub 2020 Mar 18.

Department of Endocrinology, Shanghai University of Medicine & Health Science Affiliated Zhoupu Hospital, Shanghai, China.

The expressions of antibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) are very common in the sera of patients with autoimmune thyroid diseases (AITD). The relationship between thyroid autoantibodies and the occurrence of glucose and lipid metabolic disorders remains unclear. This study was performed to investigate the correlation between the presence of serum TPOAb/TgAb and those metabolic disorders in euthyroid general population. The data of this study were derived from the Thyroid Disease, Iodine status, and Diabetes National epidemiological (TIDE) survey from all 31 provinces of mainland China. A total of 17,964 euthyroid subjects including 5,802 males (4,000 with TPOAbTgAb and 1,802 with TPOAb/TgAb) and 12,162 females (8,000 with TPOAbTgAb and 4,162 with TPOAb/TgAb) were enrolled in this study. The blood glucose and lipid levels were compared between individuals with TPOAbTgAb and those with TPOAbTgAb, TPOAbTgAb, TPOAbTgAb. Both fasting blood glucose (FBG) concentration and the proportion of individuals with impaired FBG (IFG) showed the decreased trends in TPOAbTgAb males as compared with TPOAbTgAb men. There were significantly lower FBG and higher HDL-C levels as well as tendencies toward decreased incidences of IGT and hypertriglyceridemia in TPOAbTgAb females when compared with TPOAbTgAb women. Binary logistic regression analysis further showed that serum TgAb single positivity in males was an independent protective factor for IFG with an OR of 0.691 (95% CI, 0.503-0.949). For females, serum TgAb single positivity was an independent protective factor for hypertriglyceridemia with an OR of 0.859 (95% CI, 0.748-0.987). Trend test showed that with the increase of serum TgAb level, there were significant decreases in the prevalence of IFG among the men with TSH ≤ 2.5 mIU/L and that of hypertriglyceridemia in the women, especially among non-obese females. Serum TgAb single positivity may imply a reduced risk of IFG in euthyroid men and that of hypertriglyceridemia in euthyroid women. The mechanisms for the independent protective roles of TgAb await further investigation.
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http://dx.doi.org/10.3389/fendo.2020.00139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093715PMC
February 2021

U-Shaped Associations Between Urinary Iodine Concentration and the Prevalence of Metabolic Disorders: A Cross-Sectional Study.

Thyroid 2020 07 27;30(7):1053-1065. Epub 2020 Apr 27.

Department of Endocrinology and Metabolism, People's Hospital of Tibet Autonomous Region, Lhasa, P.R. China.

Iodine is important in both thyroid function and human metabolism. Studies have explored the effect of iodine on metabolic disorders through thyroid function. This study aimed to investigate the relationship between iodine status and metabolic disorders, such as metabolic syndrome (MetS), hypertension, impaired glucose metabolism, central obesity, and dyslipidemia. A total of 51,795 subjects aged ≥18 years from the TIDE (Thyroid Disorders, Iodine Status and Diabetes, a national epidemiological cross-sectional study) program were included. The prevalence of metabolic disorders and its related diseases was calculated based on the level of urinary iodine concentrations (UICs) using the chi-square method. To further explore whether the prevalence was associated with UIC, quadratic and UIC-stratified logistic regression models were used. The prevalence of metabolic disorders as a function of UIC was found to be U-shaped with a lower prevalence of 76.0% at an UIC of 300-499 μg/L. Participants with an UIC of 300-499 μg/L showed an association with metabolic disorders (odds ratio [OR] = 0.857, 95% confidence interval [CI 0.796-0.922]) and hypertension (OR = 0.873 [CI 0.814-0.936]). An UIC of 300-799 μg/L was found to be associated with the occurrence of MetS and impaired glucose tolerance. An UIC of 500-799 μg/L was associated with the occurrence of prediabetes (OR = 0.883 [CI 0.797-0.978]). An UIC of ≥300 μg/L was associated with the occurrence of hypertriglyceridemia, hypercholesterolemia, and high levels of low-density lipoprotein cholesterol. Furthermore, an UIC of <100 μg/L showed an association with hypertension (OR = 1.097 [CI 1.035-1.162]) and hypercholesterolemia (OR = 1.178 [CI 1.117-1.242]). The association between UICs in adults and metabolic disorders and its related diseases is U-shaped. The association between UIC and metabolic disorders disappears in cases of iodine deficiency (<100 μg/L) or excess (≥500 μg/L).
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http://dx.doi.org/10.1089/thy.2019.0516DOI Listing
July 2020

A negative association between urinary iodine concentration and the prevalence of hyperuricemia and gout: a cross-sectional and population-based study in Mainland China.

Eur J Nutr 2020 Dec 20;59(8):3659-3668. Epub 2020 Feb 20.

Department of Endocrinology, Qinghai Provincial People's Hospital, Xining, 810000, Qinghai, People's Republic of China.

Background And Aims: Iodine is one of the most important trace elements in the human body. It is not only the main component of thyroid hormones but also has extrathyroid biological functions. To date, there have been no large-scale epidemiological studies on the relationship between hyperuricemia and iodine intake, although both are closely related to health. A population-based epidemiological survey in China offers such an opportunity.

Methods: This population-based cross-sectional study recruited 75,653 adults aged ≥ 18 years from 2015 to 2017 with a randomized, multistage, stratified sampling strategy. Serum uric acid levels and urinary iodine concentrations (UICs) were measured.

Results: Stratified by UIC, the prevalence of hyperuricemia was 17.8%, 18.8%, 16.0% and 13.7% in the UIC < 100, 100-199, 200-299, and ≥ 300 μg/L groups, respectively; the prevalence of gout was 4.0%, 3.4%, 2.4% and 1.7%, respectively. The prevalence of gout decreased significantly as the UIC increased. The prevalence of hyperuricemia and gout were markedly higher in postmenopausal females than in the premenopausal population (hyperuricemia: 15.9% vs. 8.3%, X = 520.072, p < 0.001; gout: 3.6% vs. 1.3%, X = 219.889, p < 0.001), and the prevalence decreased as the UIC increased. Subjects in the more than adequate and excessive iodine groups had lower likelihoods of having hyperuricemia [aOR = 0.81 (95% CI 0.77-0.85), aOR = 0.68 (95% CI 0.64-0.72)] and lower odds of having gout than subjects in the adequate iodine (AI) group [aOR = 0.77 (95% CI 0.68-0.86), aOR = 0.59 (95% CI 0.51-0.68)].

Conclusions: UIC was inversely associated with the occurrence of hyperuricemia and gout. More in-depth research and prospective studies are needed to explore the molecular mechanisms and confirm the observed association.
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http://dx.doi.org/10.1007/s00394-020-02199-zDOI Listing
December 2020

Efficacy and Safety of Long-Term Universal Salt Iodization on Thyroid Disorders: Epidemiological Evidence from 31 Provinces of Mainland China.

Thyroid 2020 04 24;30(4):568-579. Epub 2020 Mar 24.

Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, P.R. China.

Mandatory universal salt iodization (USI) has been implemented in China for 20 years. Although iodine deficiency disorders are effectively controlled, the risk of excess iodine have been debated. A nationally representative cross-sectional study with 78,470 enrolled participants, aged 18 years or older, from all 31 provincial regions of mainland China was performed. The participants were given a questionnaire and underwent B-mode ultrasonography of the thyroid. Serum concentrations of thyroid hormones, thyroid antibodies, and urine iodine concentration (UIC) were measured. The median UIC of the adult population was 177.89 μg/L. The weighted prevalence of thyroid disorders in adults were as follows: 0.78% of overt hyperthyroidism, 0.44% of subclinical hyperthyroidism, 0.53% of Graves' disease, 1.02% of overt hypothyroidism, 12.93% of subclinical hypothyroidism, 14.19% of positive thyroid antibodies, 10.19% of positive thyroid peroxidase antibodies, 9.70% of positive thyroglobulin antibodies, 1.17% of goiter, and 20.43% of thyroid nodules. Iodine excess was only associated with higher odds of overt hyperthyroidism and subclinical hypothyroidism, while iodine deficiency was significantly associated with higher odds of most thyroid disorders. In addition, increased iodine intake was significantly associated with elevated serum thyrotropin levels but was inversely associated with thyroid antibodies and thyroid nodules. The long-term mandatory USI program with timely adjustments is successful in preventing iodine deficiency disorders, and it appears to be safe. The benefits outweigh the risks in a population with a stable median iodine intake level of up to 300 μg/L.
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http://dx.doi.org/10.1089/thy.2019.0067DOI Listing
April 2020

The potential markers involved in newly diagnosed graves' disease and the development of active graves' orbitopathy.

Cytokine 2020 03 20;127:154998. Epub 2020 Jan 20.

Department of Endocrinology, the First Affiliated Hospital of Xi'an JiaoTong University, Xi'an, Shaanxi, 710061, PR China.. Electronic address:

Background: Graves' disease (GD) patients experience two major issues: one is the severe hyperthyroidism associated with newly diagnosed GD, and the other involves the disfiguring and dysfunctional features of active Graves' orbitopathy (GO). Therefore, the aim of our study was to identify potential markers involved in the initial phase of GD dysfunction and the development of active GO.

Methods: Seventy-eight subjects were recruited: 40 with newly diagnosed GD, 20 with inactive GO and 18 with active GO. GO activity was evaluated by the clinical activity score (CAS, active GO = CAS ≥ 3), and severity was assessed according to the NOSPECS classification. Plasma selenium concentrations were determined by dual channel hydride generation atomic fluorescence photometry. A liquid chip assay was used to measure plasma Th1 cytokines IFN-γ and TNF-α; Th2 cytokines IL4, IL5 and IL6; Th17 cytokine IL23; Treg cytokines IL10 and TGF-β; and two chemokines, CCL2 (Th2 chemokine) and CXCL10 (Th1 chemokine).

Results: Among the three groups, newly diagnosed GD patients showed significantly elevated plasma levels of CXCL10 and IL-23 (all p < 0.05). Both CXCL10 and IL23 were significantly correlated with hyperthyroidism severity, specifically, increasing FT3 and FT4 and decreasing TSH. Notably, a very strong positive relationship between IL23 and CXCL10 was revealed (adjusted R square = 0.795; p < 0.001). Moreover, the selenium level was lower, while that of CCL2 was higher, in active GO than in inactive GO (p = 0.007, p < 0.001, respectively). Likewise, we also discovered that increasing CCL2 levels and decreasing selenium levels were associated with high CAS. Remarkably, after adjusting for potential confounding factors, selenium (OR, 0.919) and CCL2 (OR, 1.042) were still independent predictors for the diagnosis of active GO, and similar conclusions were drawn by receiver operating characteristic (ROC) curve analysis.

Conclusion: Pro-inflammatory cytokines, especially Th17-associated cytokines (e.g., IL23) and Th1 chemokines (e.g., CXCL10), appear to be involved in the initial phase of GD dysfunction. Moreover, we revealed for the first time that decreased plasma selenium levels and increased concentrations of Th2 chemokines (e.g., CCL2) may reflect GO disease activity, shedding light on the diagnosis and evaluation of active GO.
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http://dx.doi.org/10.1016/j.cyto.2020.154998DOI Listing
March 2020

Islet Function Changes Among the Elderly Population.

Arch Med Res 2019 10 17;50(7):468-475. Epub 2020 Jan 17.

Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, PR China. Electronic address:

Background: China is stepping into the aging society. The prevalence of type 2 diabetes among elderly population is increasing in China in the last few decades. However, there is a lack of epidemiological investigations regarding to the aging-related changes of islet function in the elderly population.

Objective: To investigate the islet function and glycemic conditions in the elderly population of western China.

Methods: Using a complex, multistage, probability sampling design, we conducted a cross-sectional survey in a provincial representative sample of 3001 western Chinese elderly adults. A 2 h oral glucose tolerance test (OGTT) was conducted among all study participants, and islet function measurements including HOMA-β, HOMA-IR, HOMA-IS, ΔI30/ΔG30, Ip/I0 were calculated.

Results: HOMA-β, HOMA-IR and ΔI30/ΔG30 decreased gradually along with increasing age from age of 55 to age of 80 (p <0.05). HOMA-IR, HOMA-β and ΔI30/ΔG30 were significantly higher while HOMA-IS lower among urban residents than rural residents or suburb residents (p <0.01). FPG, 2 h plasma glucose (P2hPG) and HbA1C increased with increasing age (p <0.05), while fasting insulin level (FINS) and 2 h insulin level (P2hINS) decreased with increasing age (p <0.05). FPG, P2hPG and glycated hemoglobin (HbA1C) among suburb residents were lower than among urban residents and among rural residents (p <0.05).

Conclusion: Islet function decreased gradually along with increasing age with no gender difference among the elderly population in western China. Glycemic outcomes became worse with increasing age. These results indicated that strategies aimed at the prevention of diabetes in the elderly population were needed.
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http://dx.doi.org/10.1016/j.arcmed.2019.10.013DOI Listing
October 2019

The proportion of peripheral blood Tregs among the CD4+ T cells of autoimmune thyroid disease patients: a meta-analysis.

Endocr J 2020 Mar 10;67(3):317-326. Epub 2019 Dec 10.

Department of Endocrinology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.

Autoimmune thyroid disease (AITD) is characterized by a loss of self-tolerance to thyroid antigen. Tregs, whose proportions are controversial among CD4+ T cell from AITD patients (AITDs), are crucial in immune tolerance. Considering that drugs might affect Treg levels, we assumed that the differences originated from different treatment statuses. Thus, we performed a meta-analysis to explore proportions of Tregs in untreated and treated AITDs. PubMed, Embase and ISI Web of Knowledge were searched for relevant studies. Review Manager 5.3 and Stata 14.0 were used to conduct the meta-analysis. Subgroup analysis based on different diseases and cell surface markers was performed. Egger linear regression analysis was used to assess publication bias. Approximately 1,100 AITDs and healthy controls (HCs) from fourteen studies were included. Proportions of Tregs among CD4+ T cells of untreated AITDs were significantly lower than those in HCs (p = 0.002), but were not in treated patients (p = 0.40). Subgroup analysis revealed lower proportions of Tregs in untreated Graves' disease patients (GDs) (p = 0.001) but did not show obvious differences in untreated Hashimoto's thyroiditis patients (HTs) (p = 0.62). Furthermore, proportions of circulating FoxP3+ Tregs were reduced in untreated GDs (p < 0.00001) and HTs (p = 0.04). No publication bias was found. In this first meta-analysis exploring proportions of circulating Tregs among CD4+ T cells of AITDs with different treatment statuses, we found that Tregs potentially contribute to the pathogenesis of AITD but function differently in GD and HT. Remarkably, FoxP3+ Tregs, which were decreased in both diseases, might be promising targets for novel therapies.
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http://dx.doi.org/10.1507/endocrj.EJ19-0307DOI Listing
March 2020

The association between cigarette smoking and serum thyroid stimulating hormone, thyroid peroxidase antibodies and thyroglobulin antibodies levels in Chinese residents: A cross-sectional study in 10 cities.

PLoS One 2019 25;14(11):e0225435. Epub 2019 Nov 25.

Department of Endocrinology and Metabolism, Key Laboratory of Thyroid Diseases in Liaoning Province, The First Hospital of China Medical University, Shenyang, China.

Objectives: Although several studies have shown that cigarette smoking is associated with thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb), the exact relationship between smoking and thyroid function is controversial. As little is known about the effects of smoking on TSH, TPOAb and TgAb in Chinese residents. This study aimed to evaluate the association between cigarette smoking and TSH, TPOAb and TgAb in ten-city residents of China.

Study Design: This was a population-based cross-sectional study.

Methods: In this cross-sectional study, 15,181 subjects from ten major cities of China were investigated. Data regarding demographic characteristics, smoking status and consumption of iodine status were collected using in-person interviews based on a self-designed structured questionnaire. Serum concentrations of TSH, TPOAb and TgAb were measured using electrochemiluminescence immunoassays. Univariate analysis and multivariate linear stepwise regression analyses were used to analyze the data.

Results: The regular smokers had lower concentrations of TSH, TPOAb and TgAb than occasional smokers, former smokers and never smokers. Multivariate analysis demonstrated that regular smoking was associated with the decreased concentrations of TSH (β = -0.178), TPOAb (β = -0.287) and TGAb (β = -0.453) after adjusting other factors. Furthermore, daily smoking number was significantly associated with the decreased level of TSH (β = -0.045) and TPOAb(β = -0.080), and smoking duration was associated with the decreased TSH level (β = -0.030).

Conclusions: Our findings suggest that cigarette smoking is related to a significant decline in the concentrations of TSH, TPOAb and TgAb. In addition, daily smoking number and long-term smoking decrease serum TSH and TPOAb levels. Cigarette smoking plays a significant role in the development of thyroid dysfunction.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0225435PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6876836PMC
March 2020

Sphingolipid metabolism in type 2 diabetes and associated cardiovascular complications.

Exp Ther Med 2019 Nov 6;18(5):3603-3614. Epub 2019 Sep 6.

Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.

Sphingolipid metabolism is dysregulated in type 2 diabetes mellitus (T2DM); however, the focus of previous studies was mostly limited to ceramide (Cer), and only few studies have investigated other metabolites, including sphingosine-1 phosphate (So1P). The present study aimed to examine the involvement of 8 major sphingolipid metabolites, including Cer, glucosyl ceramide (GluCer), lactosyl ceramide (LacCer), sphingomyelin (SM), sphinganine (Sa), So1P, sphingosine (So) and sphinganine-1-phosphate (Sa1P), during the progression of T2DM, and to evaluate the ability of serum sphingolipids to predict cases of diabetes with an elevated risk of cardiovascular complications. Blood samples were obtained from 245 participants who were divided into 3 groups: Healthy controls, pre-diabetes (pre-DM) and diagnosed diabetes. The 8 major sphingolipid metabolites were measured by high-performance liquid chromatography-tandem mass spectrometry and blood parameters were determined by routine laboratory assays for all subjects. Among the sphingolipid metabolites, So1P was associated with sex and lean mass index, but not with the body mass index. So1P was highest in healthy controls and gradually decreased when the disease proceeded to pre-DM and T2DM. GluCer, SM, Sa and So decreased in pre-DM and rose again in T2DM, graphically exhibiting a 'U' shape change during the progression of diabetes. So1P and Sa were identified to be significantly associated with cardiovascular complications by multivariate logistic regression analysis. Receiver operating characteristic curve analysis also suggested that So1P and Sa were able to indicate cardiovascular complications in diabetic patients. Pre-DM and diabetes were significantly associated with decreased So1P, SM, Sa and So, compared with the healthy controls. So1P was correlated with the progression of T2DM, and was a predictor of an elevated risk of cardiovascular complications among T2DM patients, along with Sa. The present study was registered with ClinicalTrials.gov (no. NCT02826759; April 2016).
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http://dx.doi.org/10.3892/etm.2019.7981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6777336PMC
November 2019

Sphingosine-1-phosphate induces islet β-cell proliferation and decreases cell apoptosis in high-fat diet/streptozotocin diabetic mice.

Exp Ther Med 2019 Nov 11;18(5):3415-3424. Epub 2019 Sep 11.

Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.

Sphingosine-1-phosphate (S1P) has been reported to enhance the function of islet β-cells, providing a potential therapeutic target for diabetes mellitus. In the present study, the effects of S1P on the proliferation and apoptosis of β-cells in type 2 diabetic mice were investigated. The mice were administered intraperitoneal S1P solution daily at a dose of 20 µg/kg for three weeks. The intraperitoneal glucose tolerance test (IPGTT) and homeostatic model assessment of insulin resistance (HOMA-IR) index determination were carried out. Immunohistochemical staining was used to detect the protein expression of insulin, antigen Ki-67 and S1P receptor isoforms (S1PR1/S1PR2/S1PR3) in pancreatic islets. Compared with the diabetic control (DC) group, the IPGTT results and HOMA-IR index in the S1P treatment group were decreased. The islets in the S1P group exhibited higher insulin immunostaining intensity than the DC group, as well as higher proliferation (P<0.05) and lower apoptosis rates (P<0.05). Positive staining for the S1P receptors S1PR1, S1PR2 and S1PR3 was observed in the cytoplasm and membrane of the islet cells. S1PR1 and S1PR2 proteins showed increased expression in the S1P and DC groups compared with the normal control group (P<0.01 and P<0.05, respectively), whereas no significant difference was observed in the expression of S1PR3 among these groups. In conclusion, extracellular S1P can induce islet β-cell proliferation and decrease cell apoptosis in diabetic mice. S1P function may be mediated via S1PR1 and S1PR2; therefore, targeting S1P/S1PR signalling pathways may be a novel therapeutic strategy for diabetes mellitus.
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http://dx.doi.org/10.3892/etm.2019.7999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6777293PMC
November 2019

A Randomized, Double-Blind, Non-Inferiority Study of Febuxostat Versus Allopurinol in Hyperuricemic Chinese Subjects With or Without Gout.

Rheumatol Ther 2019 Dec 17;6(4):543-557. Epub 2019 Sep 17.

Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Zhabei, Shanghai, China.

Introduction: This 24-week randomized, double-blind, non-inferiority study compared the efficacy and safety of febuxostat, a xanthine oxidase inhibitor, with allopurinol using an up-titration method in hyperuricemic Chinese subjects with or without gout.

Methods: Eligible adults (serum uric acid [SUA] > 7.0 mg/dl with a history of gout, SUA ≥ 8.0 mg/dl with complications or SUA ≥ 9.0 mg/dl without complications) were randomized (1:1:1) to febuxostat 40 mg/day, 80 mg/day, or allopurinol 300 mg/day. Starting doses of febuxostat 20 mg/day and allopurinol 100 mg/day were up-titrated, up to 16 weeks, to the randomized doses and maintained to week 24. Primary endpoint was non-inferiority of febuxostat 40 mg/day versus allopurinol 300 mg/day based on the percentage of subjects with SUA ≤ 6.0 mg/dl at week 24. The same comparison was made between febuxostat 60 mg/day or 80 mg/day versus allopurinol 300 mg/day. Safety assessments included measurement of treatment-emergent adverse events (TEAEs).

Results: The per-protocol population comprised 472 subjects. Non-inferiority of febuxostat 40 mg/day versus allopurinol 300 mg/day was not demonstrated based on the protocol-defined margin of - 10% (44.7 vs. 50.0%; - 5.3% difference; 95% confidence interval [CI]: - 16.4%, 5.8%); however, superiority over allopurinol 300 mg/day was demonstrated for febuxostat 60 mg/day at week 16 (66.3 vs. 51.2%; a 15.0% difference; 95% CI: 4.2%, 25.9%) and febuxostat 80 mg/day at week 24 (70.0 vs. 50.0%; a 20.0% difference; 95% CI: 9.3%, 30.7%). The frequency of TEAEs was similar across groups, with gout flares occurring frequently.

Conclusions: Using a novel dose-titration method, although the primary endpoint of non-inferiority of febuxostat 40 mg/day versus allopurinol 300 mg/day was not reached, non-inferiority and superiority of febuxostat 60 mg/day and 80 mg/day versus allopurinol 300 mg/day was demonstrated at weeks 16 and 24, respectively. Febuxostat demonstrated an acceptable tolerability profile in the treatment of hyperuricemia in Chinese subjects with or without gout.

Trial Registration: JapicCTI-132106.

Funding: Astellas Pharma Global Development, Inc.
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http://dx.doi.org/10.1007/s40744-019-00173-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858416PMC
December 2019