Publications by authors named "Zhongyan Shan"

243 Publications

Lumbar Scheuermann's disease found in a patient with osteogenesis imperfecta (OI) caused by a heterozygous mutation in COL1A2 (c.4048G > A): a case report.

BMC Musculoskelet Disord 2021 Jun 7;22(1):525. Epub 2021 Jun 7.

Department of Endocrinology and Metabolism, Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Affiliated Hospital of China Medical University, Shenyang, P. R. China.

Background: Osteogenesis imperfecta (OI) is a heterogeneous connective tissue disorder characterized by increased bone fragility and a series of extraskeletal manifestations. Approximately 90 % of OI cases are caused by type I collagen variants encoded by the collagen type I alpha 1 (COL1A1) or type I alpha 2 (COL1A2) gene. Lumbar Scheuermann's disease is an atypical type of Scheuermann's disease accompanied by Schmorl's nodes and irregular endplates but without pronounced kyphosis. Although the etiology of Scheuermann's disease is unclear, genetic and environmental factors are likely.

Case Presentation: Here, we report a 32-year-old male patient who experienced multiple brittle fractures. Gene sequencing revealed a heterozygous mutation, c.4048G > A (p.G1350S), in the COL1A2 gene, and the patient was diagnosed with OI. Magnetic resonance imaging of his thoracolumbar spine revealed multiple Schmorl's nodes.

Conclusions: This is the first reported case of OI coexisting with the spinal presentation of Scheuermann's disease. It is speculated that the COL1A2 gene mutation might be an underlying novel genetic cause of Scheuermann's disease. In conclusion, this case demonstrates the relationship between Scheuermann's disease and OI for the first time and enriches the genotype-phenotype spectrum of OI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12891-021-04401-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185920PMC
June 2021

Maternal Subclinical Hypothyroidism in Rats Impairs Spatial Learning and Memory in Offspring by Disrupting Balance of the TrkA/p75 Signal Pathway.

Mol Neurobiol 2021 May 8. Epub 2021 May 8.

Department of Endocrinology and Metabolism, Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, No. 155 Nanjing North Street, Shenyang, 110001, China.

Maternal subclinical hypothyroidism (SCH) during pregnancy can adversely affect the neurodevelopment of the offspring. The balance of nerve growth factor (NGF)-related tropomyosin receptor kinase A/p75 neurotrophin receptor (TrkA/p75) signaling in the hippocampus is important in brain development, and whether it affects cognitive function in maternal SCH's offspring is not clear. In this study, we found that compared with the control (CON) group, expression of proliferation-related proteins [NGF, p-TrkA, phospho-extracellular signal-regulated kinase 1/2 (p-ERK1/2) and phospho-cAMP response element-binding protein (p-CREB)] decreased in the hippocampus of the offspring in the SCH group, overt hypothyroidism (OHT) group, and the group with levothyroxine (L-T) treatment for SCH from gestational day 17 (E17). In contrast, expression of apoptosis-related proteins [pro-NGF, p75, phospho-C-Jun N-terminal kinase (p-JNK), p53, Bax and cleaved caspase-3] was increased. The two groups with treatment with L-T for SCH from E10 and E13, respectively, showed no significant difference compared with the CON group. L-T treatment enhanced relative expression of NGF by increasing NGF/proNGF ratio in offspring from maternal SCH rats. In conclusion, L-T treatment for SCH from early pregnancy dramatically ameliorated cognitive impairment via TrkA/p75 signaling, which involved activation of the neuronal proliferation and inhibition of neuronal apoptosis in SCH rats' offspring.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12035-021-02403-zDOI Listing
May 2021

The Relationship Between Thyroid Function and Metabolic Syndrome and Its Components: A Cross-Sectional Study in a Chinese Population.

Front Endocrinol (Lausanne) 2021 31;12:661160. Epub 2021 Mar 31.

Department of Endocrinology and Metabolism, Institute of Endocrinology, The First Affiliated Hospital of China Medical University, Shenyang, China.

Objective: The present study examined the relationship between thyroid function status and the prevalence of metabolic syndrome in a Chinese population.

Methods: Cross-sectional data were obtained from the Thyroid Disease, Iodine Nutrition and Diabetes Epidemiology (TIDE) Survey. A total of 62,408 subjects aged ≥18 years were enrolled. Differences in metabolic indicators and the prevalence of metabolic syndrome according to sex and thyroid function status were compared. Logistic regression was used to analyze the influence of thyroid function on metabolic syndrome and its components.

Results: The prevalence of metabolic syndrome was generally higher in men than women. Overt hyperthyroidism and subclinical hypothyroidism had a significant effect on metabolism in men. Body mass index (BMI), waist circumference, and triglycerides (TGs) were significantly lower in men in the overt hyperthyroidism group, and BMI, waist circumference, systolic blood pressure (SBP) and TGs were higher in men in the subclinical hypothyroidism group than men in the normal group. Overt and subclinical hypothyroidism had significant impacts on metabolic components in women. BMI, waist circumference, TGs, SBP and DBP in the subclinical and overt hypothyroidism groups were significantly higher than the euthyroid group in women. The relative risk of abdominal obesity and hypertriglyceridemia was increased in women with hypothyroidism. Thyroid dysfunction had different effects on metabolic syndrome and its components before and after menopause.

Conclusion: Thyroid function had important effects on the prevalence of metabolic syndrome. Women with hypothyroidism, especially post-menopausal women, had a higher risk of metabolic syndrome than men.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2021.661160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044548PMC
March 2021

The Iodine Status and Prevalence of Thyroid Disorders among Women of Childbearing-age in China: National Cross-sectional Study.

Endocr Pract 2021 Apr 7. Epub 2021 Apr 7.

Department of Endocrinology and Metabolism and the Institute of Endocrinology, First Hospital of China Medical University, 155 Nanjing Bei Street, Shenyang, 110001, Liaoning, China. Electronic address:

Objective: Mandatory universal salt iodization in China was implemented 20 years ago; however, the current iodine status and prevalence of thyroid disorders among childbearing-age women are unknown.

Methods: A nationally representative cross-sectional study with 26166 enrolled participants aged 18 to 49 years from all 31 provincial regions of mainland China was performed. The participants were given a questionnaire and underwent B-mode ultrasonography of the thyroid. The serum concentrations of thyroid hormones and thyroid antibodies and the urine iodine concentration (UIC) were measured.

Results: The median UIC was 178.7 μg/L, which is indicative of adequate iodine status; however, 19.04% and 19.87% of the participants were classified as having iodine deficiency and excessive iodine, respectively. The weighted prevalences of thyroid disorders were as follows: 1.08% had overt hyperthyroidism, 0.58% had subclinical hyperthyroidism, 0.76% had Graves' disease, 1.28% had overt hypothyroidism, 14.28% had subclinical hypothyroidism, 13.53% were positive for TPOAb, and 14.55% were positive for TgAb. Excessive iodine and overweight were associated with higher odds of subclinical hypothyroidism. A family history of thyroid disorders and an age between 40-49 years were significantly associated with higher odds of positivity for TPOAb and positive TgAb.

Conclusion: Iodine deficiency, excessive iodine, subclinical hypothyroidism, and positivity for thyroid autoantibodies are still prevalent among women of childbearing age in China. Women of childbearing age who are relatively older, are overweight, or have a family history of thyroid disorders are encouraged to undergo active screening of their UIC and thyroid function when planning a pregnancy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eprac.2021.03.017DOI Listing
April 2021

MicroRNA expression profiles of the thyroid after goiter formation and involution in rats under different iodine regimens.

Endocrine 2021 Mar 25. Epub 2021 Mar 25.

Department of Endocrinology and Metabolism, Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, China.

Background: Thyroid damage occurs during experimental iodine-deficient goiter and involution with iodine supplementation. This study investigated the dynamic microRNAs (miRNAs) expression profiles in iodine-deficient thyroids during adequate and excessive iodine supplementation.

Methods: Twenty-four female Wistar rats were randomly divided into control, low-iodine (LI), LI-1I, and LI-2I groups. The LI-1I and LI-2I groups were fed a LI diet for 12 weeks, followed by a onefold (adequate) or twofold (excessive) physiological dose of iodine for 4 weeks to induce involution. The miRNA expression profiles were evaluated and the potential functions of the differentially expressed miRNAs identified were explored.

Results: In the LI group, 20 miRNAs were downregulated and 8 were upregulated. After involution, 21 miRNAs recovered to the control group levels in the LI-1I group, which was more than the 17 that recovered in the LI-2I group. In addition, 8 new differentially expressed miRNAs were identified in the LI-1I group, which was less than the 13 found in the LI-2I group. Bioinformatics analyses indicated that all differentially expressed miRNAs were involved in different processes and pathways, such as autoimmune thyroid disease and the Ras signaling pathway.

Conclusion: Differentially expressed miRNAs are involved in iodine-deficient goiter formation and involution. Supplementation with adequate, not excessive, iodine may be more beneficial to restore homeostasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12020-021-02679-0DOI Listing
March 2021

Vitamin D deficiency is associated with thyroid autoimmunity: results from an epidemiological survey in Tianjin, China.

Endocrine 2021 Mar 23. Epub 2021 Mar 23.

Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, 300052, China.

Purpose: The pathogenesis of Hashimoto's thyroiditis (HT) is unclear, although some studies have identified an association between vitamin D deficiency and thyroid autoantibody positivity. This study aimed to investigate vitamin D status, and its relationships with thyroid autoantibody positivity and HT, via a large epidemiological survey.

Methods: The epidemiological survey was conducted in Tianjin, China. All participants underwent testing for serum 25-hydroxyvitamin D (25OHD), thyroid function, and thyroid autoantibodies, and some participants underwent testing to evaluate CD4 T-cell differentiation and concentrations of related cytokines.

Results: The study included 1812 participants and revealed prevalences of 13.1% for thyroid peroxidase antibodies (i-TPOAb) and 14.0% for thyroglobulin antibodies (i-TgAb). Logistic regression analysis revealed that thyroid autoantibody positivity was associated with sex, age, and 25OHD classification. An increased likelihood of i-TPOAb positivity was associated with 25OHD deficiency (odds ratio [OR]: 2.428, 95% confidence interval [CI]: 1.383-4.261) and 25OHD inadequacy (OR: 1.198, 95% CO: 0.828-1.733; p = 0.008). An increased likelihood of i-TgAb positivity was associated with 25OHD deficiency (OR: 2.366, 95% CI: 1.366-4.099) and 25OHD inadequacy (OR: 1.263, 95% CI: 0.883-1.807; p = 0.009). Relative to healthy subjects, patients with HT had significantly higher proportions of Th1 and Th17 cells, as well as higher concentrations of related cytokines.

Conclusions: This study revealed that vitamin D deficiency was associated with thyroid autoantibody positivity, and that vitamin D deficiency seems to be involved in the pathological mechanism underlying HT. Large randomized controlled trials are needed to investigate the effects of vitamin D supplementation on HT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12020-021-02688-zDOI Listing
March 2021

Causal Association between Serum Thyroid-Stimulating Hormone and Obesity: A Bidirectional Mendelian Randomization Study.

J Clin Endocrinol Metab 2021 Mar 23. Epub 2021 Mar 23.

Department of Endocrinology and Metabolism and the institute of Endocrinology, The First Hospital of China Medical University, Shenyang, Liaoning, P.R. China.

Context: The association between serum thyroid-stimulating hormone (TSH) and obesity traits has been investigated previously in several epidemiological studies. However, the underlying causal association has not been established.

Objective: To determine and analyze the causal association between serum TSH level and obesity-related traits (BMI and obesity).

Design, Setting, Participants: The latest genome-wide association studies (GWASs) on TSH, BMI and obesity were searched to obtain full statistics. Bidirectional two-sample Mendelian randomization (MR) was performed to explore the causal relationship between serum TSH and BMI and obesity. The inverse variance-weighted (IVW) and MR-Egger methods were used to combine the estimation for each SNP. Based on the preliminary MR results, free thyroxine (fT4) and free triiodothyronine (fT3) levels were also set as outcomes to further analyze the impact of BMI on them.

Main Outcome Measures: BMI and obesity were treated as the outcomes to evaluate the effect of serum TSH on them, and TSH was set as the outcome to estimate the effect of BMI and obesity on it.

Results: Both IVW and MR-Egger results indicated that genetically driven serum TSH did not causally lead to changes in BMI or obesity. Moreover, the IVW method showed that the TSH level could be significantly elevated by genetically predicted high BMI (β=0.038, se=0.013, p=0.004). In further MR analysis, the IVW method indicated that BMI could causally increase the fT3 (β=10.123, se=2.523, p<0.001) while not significantly affecting the fT4 level.

Conclusion: Together with fT3, TSH can be significantly elevated by an increase in genetically driven BMI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/clinem/dgab183DOI Listing
March 2021

Skewed Th17/Treg balance during progression and malignant transformation of oral submucous fibrosis.

Oral Dis 2021 Mar 22. Epub 2021 Mar 22.

Hunan Key Laboratory of Oral Health Research & Hunan 3D, Printing Engineering Research Center of Oral Care & Hunan Clinical Research Center of Oral Major Diseases and Oral Health Xiangya Stomatological Hospital & Xiangya School of Stomatology, Central South University, Changsha, 410008, Hunan, China.

Objectives: The aim of our study was to determine the impact of Th17/Treg imbalance on the progression and malignant transformation of oral submucosal fibrosis (OSF).

Materials And Methods: To assess Th17 and Treg expression, overall 52 peripheral blood samples from OSF, oral squamous cell carcinoma (OSCC) patients and healthy donors were analyzed by flow cytometry. 30 normal oral mucosa 72 OSF and 90 OSCC samples were analyzed by immunohistochemistry.

Results: In peripheral blood samples, in OSCC with OSF, Th17 and Treg expression were significantly higher than those in OSF and OSCC without OSF. As confirmed by immunohistochemistry. During OSF progression, Th17 and Th17/Treg ratio showed an increasing trend, while Treg expression showed a decreasing trend. Treg expression were significantly higher in OSCC with OSF than in OSF and OSCC without OSF. Whereas, the Th17/Treg ratio was significantly lower in OSCC with OSF. Treg expression were significantly correlated with smoking and clinical stage. Th17/Treg ratio was significantly associated with tumor size, lymph node metastasis and clinical stage. A low Th17/Treg ratio was significantly associated with poor prognosis.

Conclusions: Th17/Treg ratio is a potential diagnostic indicator for OSF occurrence and malignant transformation and was an independent prognostic factor for OSCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/odi.13853DOI Listing
March 2021

Association of Genetic Polymorphisms in MicroRNAs With Type 2 Diabetes Mellitus in a Chinese Population.

Front Endocrinol (Lausanne) 2020 8;11:587561. Epub 2021 Feb 8.

Department of Cardiovascular Ultrasound, The First Affiliated Hospital of China Medical University, Shenyang, China.

Introduction: MicroRNAs (miRNA) involved in the insulin signaling pathways deeply affect the pathogenesis of T2DM. The aim of this study was to assess the association between single nucleotide polymorphisms (SNP) of the related miRNAs (let-7f rs10877887, let-7a-1 rs13293512, miR-133a-1 rs8089787, miR-133a-2 rs13040413, and miR-27a rs895819) and susceptibility to type 2 diabetes mellitus (T2DM), and its possible mechanisms.

Methods: Five SNPs in miRNAs (let-7f rs10877887, let-7a-1 rs13293512, miR-133a-1 rs8089787, miR-133a-2 rs13040413, and miR-27a rs895819) involved in the insulin signaling pathways were selected and genotyped in a case-control study that enrolled 371 T2DM patients and 381 non-diabetic controls. The individual SNP association analyses, interaction analyses of SNP-SNP, SNP-environmental factors were performed. The effect the risk-associated polymorphism on regulating its mature miRNA expression was also evaluated.

Results: In overall analyses, miR-133a-2 rs13040413 and let-7a-1 rs13293512 were related to the susceptibility to T2DM. In stratified analyses, miR-133a-2 rs13040413, let-7a-1 rs13293512 and miR-27a rs895819 showed associations with T2DM in the age ≥ 60 years subgroup. Moreover, let-7a-1 rs13293512 and miR-27a rs895819 showed associations with T2DM in male subgroup. In SNP-environmental factors interaction analyses, there were interaction effects of miR-133a-2 rs13040413 with dyslipidemia, let-7a-1 rs13293512 with smoking, and let-7a-1 rs13293512 with dyslipidemia on T2DM. In SNP-SNP interaction analyses, there were also interaction effects of miR-133a-1 rs8089787 with let-7a-1 rs13293512, and miR-133a-1 rs8089787 with let-7f rs10877887 on T2DM. Furthermore, for miR-133a-2 rs13040413, the variant T allele showed a trend toward decreased miR-133a expression in comparison with the wild C allele. For let-7a-1 rs13293512, the variant C allele expressed a lower let-7a compared to the wild T allele.

Conclusion: MiRNAs polymorphisms involved in the insulin signaling pathways and the interaction effects of SNP-SNP, SNP-environmental factors were related to T2DM susceptibility in a Chinese population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2020.587561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897684PMC
May 2021

Circulating Exosomes From Patients With Graves' Disease Induce an Inflammatory Immune Response.

Endocrinology 2021 Mar;162(3)

Department of Endocrinology and Metabolism, Institute of Endocrinology, The First Hospital of China Medical University, Shenyang, China.

Exosomes are extracellular vesicles that can participate in autoimmune diseases. The purpose of this study was to explore whether circulating exosomes are involved in Graves' disease (GD) pathogenesis. In this study, serum exosomes were extracted from 26 healthy controls (HC-EXO), 26 GD patients (GD-EXO), and 7 Graves' ophthalmopathy patients (GO-EXO). For each group, the total protein content was detected, and thyrotropin receptor, insulin-like growth factor 1 receptor (IGF-1R), heat shock protein 60 (HSP60), and cluster of differentiation (CD) 63 expression were analyzed by Western blotting (WB). Healthy volunteer-derived peripheral blood mononuclear cells (PBMCs) and HC-EXO or GD-EXO were cocultured for 24 h, and immunofluorescence was used to observe the locations of the exosomes and toll-like receptor (TLR) 2/3. CD11c+TLR2+ and CD11c+TLR3+ cell percentages were determined by flow cytometry. Myeloid differentiation factor 88 (MyD88), toll/interleukin (IL)-1 receptor domain-containing adaptor inducing interferon-β (TRIF) and p-P65 expression were analyzed by WB. IL-6 and IL-1β supernatant levels were detected using enzyme-linked immunosorbent assay. The results showed that the total protein concentration was similar among GD-EXO, GO-EXO, and HC-EXO. IGF-1R and HSP60 expression was significantly higher in GD-EXO and GO-EXO than in HC-EXO. After coculturing PBMCs with GD-EXO or HC-EXO for 24 h, GD-EXO could bind to TLR2/3. GD-EXO significantly increased CD11c+TLR2+ and CD11c+TLR3+ cell percentages; MyD88, TRIF, and p-P65 protein expression; and IL-6 and IL-1β levels. In conclusion, we first demonstrated that GD-EXO and GO-EXO highly expressed IGF-1R and HSP60. GD-EXO may induce an inflammatory response through the TLR/NF-κB signaling pathway and be involved in the pathogenesis of GD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/endocr/bqaa236DOI Listing
March 2021

Estimated change in prevalence of abnormal thyroid-stimulating hormone levels in China according to the application of the kit-recommended or NACB standard reference interval.

EClinicalMedicine 2021 Feb 28;32:100723. Epub 2021 Jan 28.

Department of Endocrinology and Metabolism and the Institute of Endocrinology, First Hospital of China Medical University, 155 Nanjing Bei Street, Shenyang 110001, Liaoning, China.

Background: Both the kit-recommended and United States National Academy of Clinical Biochemistry (NACB) standard thyroid-stimulating hormone (TSH) reference intervals (RIs) are used to determine thyroid dysfunction in clinical practice and epidemiological surveys in China. However, a number of kit-recommended RIs were derived from the European or United States reference population.

Methods: A nationally representative cross-sectional study with 78,470 enrolled participants aged 18 years or older from China was performed. Serum concentrations of thyroid hormones, TSH, thyroid antibodies (by Roche Diagnostics), and urine iodine concentration (UIC) were measured.

Findings: The abnormal TSH weighted prevalence was 15.33% (95% CI, 14.24% to 16.49%) according to the kit-recommended RI and 6.89% (6.46% to 7.34%) according to the NACB standard RI. The NACB standard prevalence of abnormal TSH was associated with an absolute change in abnormal TSH prevalence of -11.20% (-12.23% to -10.18%) among women. When estimating the proportion of supranormal TSH levels according to background characteristics, the NACB standard definition decreased the prevalence by more than 10% in some categories, with the highest absolute difference of -13.92% (-15.52% to -12.33%) observed among the elderly, -12.85% (-13.68% to -12.02%) among those with UIC ≥300 μg/L, and -12.15% (-13.02% to -11.28%) among non-smokers. For subnormal TSH, with the highest absolute difference of 3.17% (2.74% to 3.61%) observed among regular smokers, 3.11% (2.49% to 3.74%) among the elderly, and 2.53% (2.29% to 2.77%) among those with BMI <25.

Interpretation: For adults in China, the NACB standard RI of TSH reveals a lower estimated prevalence of supranormal TSH levels than the kit-recommended RI. Because of the public health significance of overt and subclinical hypothyroidism and the very large population base in China, the TSH RI should be further assessed.

Funding: National Health Commission of the People's Republic of China and National Natural Science Foundation of China.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eclinm.2021.100723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848757PMC
February 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/4138657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762642PMC
May 2021

Circulating Exosomes From Patients With Graves' Disease Induce an Inflammatory Immune Response.

Endocrinology 2021 Mar;162(3)

Department of Endocrinology and Metabolism, Institute of Endocrinology, The First Hospital of China Medical University, Shenyang, China.

Exosomes are extracellular vesicles that can participate in autoimmune diseases. The purpose of this study was to explore whether circulating exosomes are involved in Graves' disease (GD) pathogenesis. In this study, serum exosomes were extracted from 26 healthy controls (HC-EXO), 26 GD patients (GD-EXO), and 7 Graves' ophthalmopathy patients (GO-EXO). For each group, the total protein content was detected, and thyrotropin receptor, insulin-like growth factor 1 receptor (IGF-1R), heat shock protein 60 (HSP60), and cluster of differentiation (CD) 63 expression were analyzed by Western blotting (WB). Healthy volunteer-derived peripheral blood mononuclear cells (PBMCs) and HC-EXO or GD-EXO were cocultured for 24 h, and immunofluorescence was used to observe the locations of the exosomes and toll-like receptor (TLR) 2/3. CD11c+TLR2+ and CD11c+TLR3+ cell percentages were determined by flow cytometry. Myeloid differentiation factor 88 (MyD88), toll/interleukin (IL)-1 receptor domain-containing adaptor inducing interferon-β (TRIF) and p-P65 expression were analyzed by WB. IL-6 and IL-1β supernatant levels were detected using enzyme-linked immunosorbent assay. The results showed that the total protein concentration was similar among GD-EXO, GO-EXO, and HC-EXO. IGF-1R and HSP60 expression was significantly higher in GD-EXO and GO-EXO than in HC-EXO. After coculturing PBMCs with GD-EXO or HC-EXO for 24 h, GD-EXO could bind to TLR2/3. GD-EXO significantly increased CD11c+TLR2+ and CD11c+TLR3+ cell percentages; MyD88, TRIF, and p-P65 protein expression; and IL-6 and IL-1β levels. In conclusion, we first demonstrated that GD-EXO and GO-EXO highly expressed IGF-1R and HSP60. GD-EXO may induce an inflammatory response through the TLR/NF-κB signaling pathway and be involved in the pathogenesis of GD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/endocr/bqaa236DOI Listing
March 2021

Beta-elemene inhibits differentiated thyroid carcinoma metastasis by reducing cellular proliferation, metabolism and invasion ability.

Ann Transl Med 2020 Oct;8(19):1232

Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, China Medical University, Shenyang, China.

Background: Accelerated glycolysis is a characteristic of carcinoma. The herb-derived compound, beta (β)-elemene, has shown promising anticancer effects against various tumors by inhibiting aerobic glycolysis. However, its activity against thyroid carcinoma and the mechanism is still unknown.

Methods: Differentiated thyroid carcinoma (DTC) cell lines, including papillary thyroid carcinoma (PTC) cell lines (IHH-4, TPC-1, K1), and follicular thyroid carcinoma (FTC) cell line (FTC133) were treated with different concentration of β-elemene. The viability of DTC cells was analyzed using the CCK8 method. Cell cycle and apoptosis analysis were performed by flow cytometry and western blotting. The cell invasion ability was evaluated in Transwell assays. Energy metabolism in living cells was measured using a Seahorse XF analyzer. The antitumor effects of β-elemene were analyzed in a nude mouse xenograft tumors model.

Results: CCK8 assays showed β-elemene significantly inhibited DTC cell proliferation in a dose- and time-dependent manner. β-elemene promoted cell apoptosis, with increased expression of cleaved caspase-9 and decreased BCL-2 expression. Transwell assays showed that β-elemene significantly inhibited the invasion ability of DTC cells. β-elemene also reduced angiogenesis by decreasing VEGF expression in DTC cells. β-elemene reduces the basal oxygen consumption rate (OCR), extracellular acidification rate (ECAR), and maximal glycolytic capacity as well as maximal respiration and ATP production. Moreover, β-elemene inhibited tumor growth in a mouse xenograft model .

Conclusions: In this study, we have provided the first evidence of the antitumor effects of β-elemene, which was shown to inhibit cell proliferation, promote apoptosis, induce cell cycle arrest, inhibit cell invasion ability and reduce angiogenesis. Furthermore, we showed that β-elemene significantly inhibits the respiratory and glycolytic ability of human DTC cells. Thus, our findings show the potential of β-elemene as a novel treatment for DTC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/atm-20-4460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607100PMC
October 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/thy.2020.0325DOI Listing
April 2021

Glucose-lowering pharmacotherapies in Chinese adults with type 2 diabetes and cardiovascular disease or chronic kidney disease. An expert consensus reported by the Chinese Diabetes Society and the Chinese Society of Endocrinology.

Diabetes Metab Res Rev 2021 May 23;37(4):e3416. Epub 2020 Nov 23.

Department of Endocrinology, Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, China.

Patients with type 2 diabetes mellitus (T2DM) are at risk of developing atherosclerotic cardiovascular disease (ASCVD) and chronic kidney disease (CKD), which are important causes of disabling and death in patients with T2DM. For the prevention and management of ASCVD or CKD, cardiovascular risk factors should be systematically evaluated, and ASCVD and CKD should be screened in patients with T2DM. In this consensus, we recommended that metformin should be used as the first-line therapy for patients with T2DM and ASCVD or very high cardiovascular risk, heart failure (HF) or CKD, and should be retained in the treatment regimen unless contraindicated or not tolerated. In patients with T2DM and established ASCVD or very high cardiovascular risk, addition of a glucagon-like peptide 1 receptor agonist (GLP-1RA) or sodium-glucose cotransporter type 2 (SGLT2) inhibitor with proven cardiovascular benefits should be considered independent of individualised glycated haemoglobin (HbA ) targets. In patients with T2DM and HF, an SGLT2 inhibitor should be preferably added regardless of HbA levels. In patients with T2DM and CKD, SGLT2 inhibitors should be preferred for the combination therapy independent of individualised HbA targets, and GLP-1RAs with proven renal benefits would be alternative if SGLT2 inhibitors are contraindicated. Moreover, the prevention of hypoglycaemia and management of multiple risk factors by comprehensive regimen, including lifestyle intervention, antihypertensive therapies, lipid-lowering treatment and antiplatelet therapies, should be kept in mind in treating patients with T2DM and ASCVD, HF or CKD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/dmrr.3416DOI Listing
May 2021

Concentration-dependent Differences in Urinary Iodine Measurements Between Inductively Coupled Plasma Mass Spectrometry and the Sandell-Kolthoff Method.

Biol Trace Elem Res 2020 Oct 9. Epub 2020 Oct 9.

Department of Endocrinology and Metabolism and the Institute of Endocrinology, First Hospital of China Medical University, No.155 Nanjing Bei Street, Shenyang, 110001, Liaoning, China.

A large amount of historical data regarding urinary iodine concentration (UIC) were measured with the Sandell-Kolthoff (S-K) method for iodine nutrition surveillance. The congruence in urinary iodine measurements between inductively coupled plasma mass spectrometry (ICP-MS) and the S-K method has been debated. A total of 2064 adult urine samples were included in the present study. The UIC measurement results obtained simultaneously by standardized ICP-MS and the S-K method were analyzed. The UIC obtained with ICP-MS was significantly higher than that obtained with the S-K method (158 μg/L vs. 148 μg/L, p < 0.001). The Bland-Altman difference plot showed a small but significant mean difference of 6.12 μg/L between the two methods. The stratified analysis showed that the correlation coefficient was higher in the UIC < 300 μg/L group than the UIC ≥ 300 μg/L group (0.93 vs. 0.88, p = 0.0001). The mean difference between the S-K and ICP-MS methods was positively correlated with the UIC. The ICP-MS and S-K methods were comparable when the UIC was less than 300 μg/L; however, UIC values between 300 and 600 μg/L should be compared with caution after considering the research objective. We do not suggest comparing UICs obtained from the ICP-MS and S-K methods in iodine monitoring studies if the UIC is greater than 600 μg/L.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12011-020-02381-8DOI Listing
October 2020

An H3K4me3 reader, BAP18 as an adaptor of COMPASS-like core subunits co-activates ERα action and associates with the sensitivity of antiestrogen in breast cancer.

Nucleic Acids Res 2020 11;48(19):10768-10784

Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, School of Life Sciences, China Medical University, Shenyang City 110122, Liaoning Province, China.

Estrogen receptor alpha (ERα) signaling pathway is essential for ERα-positive breast cancer progression and endocrine therapy resistance. Bromodomain PHD Finger Transcription Factor (BPTF) associated protein of 18kDa (BAP18) has been recognized as a crucial H3K4me3 reader. However, the whole genomic occupation of BAP18 and its biological function in breast cancer is still elusive. Here, we found that higher expression of BAP18 in ERα-positive breast cancer is positively correlated with poor prognosis. ChIP-seq analysis further demonstrated that the half estrogen response elements (EREs) and the CCCTC binding factor (CTCF) binding sites are the significant enrichment sites found in estrogen-induced BAP18 binding sites. Also, we provide the evidence to demonstrate that BAP18 as a novel co-activator of ERα is required for the recruitment of COMPASS-like core subunits to the cis-regulatory element of ERα target genes in breast cancer cells. BAP18 is recruited to the promoter regions of estrogen-induced genes, accompanied with the enrichment of the lysine 4-trimethylated histone H3 tail (H3K4me3) in the presence of E2. Furthermore, BAP18 promotes cell growth and associates the sensitivity of antiestrogen in ERα-positive breast cancer. Our data suggest that BAP18 facilitates the association between ERα and COMPASS-like core subunits, which might be an essential epigenetic therapeutic target for breast cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/nar/gkaa787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641737PMC
November 2020

Differential expression of programmed death-1 and its ligand, programmed death ligand-1 in oral squamous cell carcinoma with and without oral submucous fibrosis.

Arch Oral Biol 2020 Nov 17;119:104916. Epub 2020 Sep 17.

Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, PR China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan 410008, PR China. Electronic address:

Objective: The aim of our study was to investigate the expression of programmed death ligand-1 (PD-L1)/programmed death-1 (PD-1) between oral squamous cell carcinoma (OSCC) patients with and without oral submucous fibrosis (OSF), and its correlation with clinic-pathologic features and its prognostic value.

Methods: PD-L1 and PD-1 expression was evaluated by immunohistochemical staining, double immunofluorescent staining and real-time PCR, and the correlation of PD-L1/PD-1 expression with clinical outcome was assessed.

Results: The level of PD-L1 expression was significantly higher in OSCC with OSF than in OSCC without OSF (p = 0.006). Moreover, PD-L1 expression was strongly correlated with lymph node metastasis (p = 0.016), and advanced tumor stage (p = 0.030). Increased PD-L1 expression was positively correlated with the incidence of OSCC with OSF (p = 0.006, p = 0.008, respectively). PD-L1 expression was an independent marker of unfavorable prognosis (p = 0.035, p = 0.048, respectively). High PD-L1 expression had a significantly worse outcome in OSCC patients with OSF (p = 0.014). Double immunofluorescent staining showed that OSCC with OSF were more strongly expressed both PD-L1 and PD-1 than OSCC without OSF. Moreover, the expression of PD-L1 were upregulated in OSCC tissues than normal control (p = 0.0422), and both PD-L1 and PD-1 was significantly higher in OSCC with OSF than OSCC without OSF tissues (p = 0.0043 and, p = 0.0012, respectively).

Conclusions: The present study suggested that PD-L1 may be an unfavorable indicator for prognosis. PD-L1/PD-1 signaling might play an important role in the malignant transformation of OSF, and targeting PD-L1/PD-1 signaling may be a new therapeutic strategy for OSCC, especially in OSCC patients with OSF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.archoralbio.2020.104916DOI Listing
November 2020

Generation and Characterization of a New Resistance to Thyroid Hormone Mouse Model with Thyroid Hormone Receptor Alpha Gene Mutation.

Thyroid 2021 04 23;31(4):678-691. Epub 2020 Oct 23.

Department of Endocrinology and Metabolism, Endocrine Institute, and Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Hospital of China Medical University, Shenyang, China.

In humans, resistance to thyroid hormone (RTH) caused by mutations in the thyroid hormone receptor alpha () gene, RTHα, manifests as tissue-specific hypothyroidism and circulating thyroid hormone levels exhibit hypothyroid-like clinical features. Before the identification of patients with RTHα, several Thrα1 knock-in mouse models were generated to clarify the function of TRα1. However, the phenotypes of these mice were not consistent with the clinical presentation of RTHα in humans. For the present study, we generated an RTHα mouse model that carries the mutation found in human RTHα patients. Here, we report the gross phenotypes of this mouse RTHα model. Traditional homologous recombination gene targeting techniques were used to introduce a mutation ( in the mouse gene. The phenotypes of the resulting mice were studied and compared with clinical features observed for RTHα with . Thrα1 homozygous mice exhibited severe neurological phenotypes, such as spasticity and motor ataxia, which were similar to those observed in endemic cretinism. Thrα1 heterozygous mice reproduced most clinical manifestations of patient with RTHα, such as a normal survival rate and male fertility, as well as delayed postnatal growth and development, neurological and motor coordination deficits, and anemia. The mice had typical thyroid function with a modest increase in serum triiodothyronine (T3) levels, a low thyroxine (T4)/T3 ratio, and low reverse T3 (rT3) levels. The Thrα1 mice faithfully recapitulate the clinical features of human RTHα and thus can provide a useful tool to dissect the role of TRα1 in development and to determine the pathological mechanisms of RTHα.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/thy.2019.0733DOI Listing
April 2021

Gender-differential effects on blood glucose levels between acarbose and metformin in Chinese patients with newly diagnosed type 2 diabetes: a sub-analysis of the MARCH trial.

Endocr J 2021 Jan 10;68(1):69-79. Epub 2020 Sep 10.

China-Japan Friendship Hospital, Beijing, 100029, China.

Using the data from the trial of Metformin and AcaRbose in Chinese as the initial Hypoglycemic treatment (MARCH), this study was performed to compare the differential effects of acarbose and metformin on glucose metabolism after stratification by gender. Six hundred and forty patients who had finished the whole 48-week follow-up were included. The reduction of haemoglobin A1c (HbA) was comparable between acarbose- and metformin-treated patients among either females or males, and it was also similar between males and females treated with either acarbose or metformin for 24 and 48 weeks. The dropping of fasting plasma glucose (FPG) in acarbose-treated females was significantly less than that in metformin-treated females at both 24 and 48 weeks. Furthermore, the decrease of 2-hour postprandial glucose (2hPPG) in acarbose-treated males was significantly greater than that in metformin-treated males at both 24 and 48 weeks. Multiple linear regression analysis showed that drug selection was an independent factor affecting the decrease of FPG in female patients while it independently influenced 2hPPG in males at week 24 and 48. The reductions of FPG and 2hPPG at week 24 and 48 were also significantly different between metformin-treated females and metformin-treated males although gender was not an independent regulating factor. Our study indicates that there might be gender-differential effects on FPG and 2hPPG reduction when the comparisons are made between acarbose and metformin treatments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1507/endocrj.EJ20-0006DOI Listing
January 2021

Dynamic Changes in Antithyroperoxidase and Antithyroglobulin Antibodies Suggest an Increased Risk for Abnormal Thyrotropin Levels.

Front Endocrinol (Lausanne) 2020 4;11:521. Epub 2020 Aug 4.

Department of Endocrinology and Metabolism, The Institute of Endocrinology, The First Hospital of China Medical University, Shenyang, China.

Antithyroperoxidase (TPOAb) and antithyroglobulin (TgAb) antibodies are associated with abnormal thyrotropin (TSH) levels. However, the effect of dynamic changes in TPOAb and TgAb on incident abnormal TSH is unknown. A total of 2,387 euthyroid participants aged 18 years or older from three rural areas in northern China were enrolled in this cohort study. Questionnaire interviews and laboratory measurements were performed at baseline in 1999 and at follow-up in 2004. Multinomial logistic regression was used to examine the relationship between changes in thyroid antibodies and incident abnormal TSH levels. In this 5 year follow-up study, TPOAb tier gain was significantly associated with an increased risk of subnormal TSH levels (adjusted RR, 1.535; 95% CI: 1.357-1.736) and supranormal TSH levels (adjusted RR, 1.378; 95% CI: 1.196-1.587), and TgAb tier gain was significantly associated with an increased risk of supranormal (adjusted RR, 1.090; 95% CI: 1.007-1.179) TSH levels. Both thyroid antibody-positive seroconversion and persistent positivity were significantly associated with an increased risk of incident abnormal TSH levels. Thyroid antibody positive seroconversion was associated with a higher risk of incident subnormal TSH than incident supranormal TSH, whereas persistent positive thyroid antibody was associated with a higher risk of incident supranormal TSH than incident subnormal TSH. Dynamic thyroid antibody changes may be related to incident abnormal TSH levels. Those with persistent positive thyroid antibody were more likely to have supranormal TSH than subnormal TSH, and those with positive seroconversion were more likely to have subnormal TSH than supranormal TSH. Further studies are needed to confirm this conclusion and to explore this association mediated by TSH receptor antibodies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2020.00521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7417360PMC
June 2021

The combination of ATA classification and FNA results can improve the diagnostic efficiency of malignant thyroid nodules.

Endocr Connect 2020 Sep;9(9):903-911

Department of Endocrinology and Metabolism, Institute of Endocrinology, The First Affiliated Hospital of China Medical University, Shenyang, China.

Purpose: To determine the diagnostic efficiency of the ATA classification and ultrasound-guided fine-needle aspiration (FNA) results in identifying the risk factors of malignancy, we analyzed the thyroid nodules of patients who underwent thyroidectomy and compared preoperative ATA classifications with FNA results.

Methods: We retrospectively analyzed 274 nodules of 196 patients who underwent ultrasonography, FNA and thyroidectomy. Histopathological findings of thyroid nodules were considered as the Au standard in the analysis of the diagnostic efficiency of the ATA classification and FNA results. Univariate analysis and binary multivariate logistic regression analysis were applied to identify the ultrasound features associated with malignancy.

Results: The overall malignancy rate of 274 nodules was 41.6%. The areas under the ROC curves (AUCs) for the ATA classification and FNA results were 0.88 and 0.878, respectively (P < 0.001). The sensitivity and specificity of the ATA classification were 86 and 86.9%, whereas those of FNA results were 68.5 and 91.4%, respectively. The specificity (98.7%) and sensitivity (94.3%) increased after the combined use of the ATA classification and FNA results. Taller-than-wide shape, microcalcifications, hypoechogenicity and irregular margins were independent risk factors for malignancy. Microcalcifications had the highest OR (7.58), and taller-than-wide shape had the highest specificity in BSRTC I, II, III and IV cytology.

Conclusion: The diagnostic efficiency of the ATA classification and FNA results in identifying malignant nodules was high, and the use of both criteria improved the diagnostic accuracy. Taller-than-wide shape, microcalcifications, hypoechogenicity and irregular margins were independent risk factors for malignancy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1530/EC-20-0303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583133PMC
September 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/thy.2020.0037DOI Listing
November 2020

Serum CA125 Level Is Associated with Diabetic Retinopathy in Chinese Patients with Type 2 Diabetes.

Diabetes Metab Syndr Obes 2020 22;13:1803-1812. Epub 2020 May 22.

Department of Ophthalmology, The First Hospital of China Medical University, Shenyang 110001, People's Republic of China.

Background: To investigate the association between serum carbohydrate antigen 125 (CA125) and the presence as well as severity of diabetes retinopathy (DR) in Chinese adult patients with type 2 diabetes.

Methods: A hospital-based cross-sectional study was conducted from February 2012 to November 2018. DR was assessed using Early Treatment Diabetic Retinopathy Study criteria. Vision-threatening DR (VTDR) was diagnosed if subjects had severe non-proliferative DR (NPDR), proliferative DR (PDR), or clinically significant macular edema (CSME). Multivariate logistic regression models were applied to explore the associations.

Results: Among the 2696 participants, the overall prevalence of DR was 25.1%, of which the prevalence of mild NPDR, moderate NPDR, and VTDR was 10.8%, 4.5%, and 9.9%, respectively. Serum CA125 level was significantly higher in participants with DR and increased with the severity of DR ( = 0.013). After accounting for age, gender, smoking, drinking, duration of diabetes, anti-diabetic agents use, systolic blood pressure, pulse pressure, weight, hemoglobin A1c and fasting plasma glucose levels, CA125 level was significantly associated with subjects in any-severity DR (odds ratio [OR] 1.006 [95% confidence interval CI: 1.002-1.010], = 0.006) and VTDR (1.008 [1.003-1.013], = 0.001). When CA125 was treated as categorized variables, the prevalence of VTDR might increase as improving CA125 quartiles ( value for trend = 0.017).

Conclusion: In this study, serum CA125 level was associated with the presence and severity of DR in Chinese patients with type 2 diabetes. Further prospective studies should be warranted to validate the feasible role of CA125 as well as other biomarkers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/DMSO.S250928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7250309PMC
May 2020

Insulin delivery with a needle-free insulin injector versus a conventional insulin pen in Chinese patients with type 2 diabetes mellitus: A 16-week, multicenter, randomized clinical trial (the FREE study).

EClinicalMedicine 2020 Jun 4;23:100368. Epub 2020 Jun 4.

Department of Endocrinology, the First Affiliated Hospital of China Medical University, Shenyang, China.

Background: Insulin therapy is poorly accepted by patients with type 2 diabetes mellitus (T2DM). A needle-free insulin injector has been developed for patients who fear injections or are reluctant to initiate insulin therapy when it is clearly indicated. The objective of this trial was to evaluate the glucose-lowering effect, tolerability, patient satisfaction and compliance with insulin treatment via a needle-free insulin injector (NFII) compared with insulin treatment via a conventional insulin pen (CIP) in patients with T2DM.

Methods: A total of 427 patients with T2DM were enrolled in a prospective, multicenter, randomized, open-label study, and were randomly assigned 1:1 to receive 16 weeks' treatment with basal insulin or premixed insulin administered either by a NFII or CIP.

Trial Registration: ClinicalTrials.gov (NCT03243903).

Findings: In the 412 patients who completed the study, the adjusted mean reduction of HbA1c from baseline at week 16 in the NFII group was 0.55% (95% CI -0.71, -0.39), which was non-inferior and statistically superior to the HbA1c reduction in the CIP group (0.26%, 95% CI -0.42, -0.11). Patients in the NFII group showed significantly higher treatment satisfaction scores than those in the CIP group (mean scores, 8.17 ± 1.78 vs. 7.21 ± 2.22, respectively; <0.0001). The occurrence of hypoglycemia was similar in the two groups, and the NFII group showed reduced incidences of skin scratches, indurations and lower VAS pain scores.

Interpretation: Insulin therapy through needle-free injector showed a non-inferior glycemic-lowering effect and a significantly enhanced level of patient satisfaction with insulin treatment compared with conventional insulin therapy through needle injections. In addition, the needle-free injector also had a better safety profile.

Funding: This study were funded by Beijing QS Medical Technology Co., Ltd, as well as The Major Chronic Non-communicable Disease Prevention and Control Research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eclinm.2020.100368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283138PMC
June 2020

Experimental evidence for alpha enolase as one potential autoantigen in the pathogenesis of both autoimmune thyroiditis and its related encephalopathy.

Int Immunopharmacol 2020 Aug 19;85:106563. Epub 2020 May 19.

Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang 110001, PR China.

Alpha-enolase (ENO1) is a ubiquitous protein. Patients with autoimmune thyroiditis-associated encephalopathy have high serum ENO1Ab titers. We aimed to explore whether ENO1Ab was the pathogenic antibody in the thyroid and brain. The serum ENO1Ab titers were significantly increased in the mice immunized with Thyroglobulin (Tg). And in the mice immunized with ENO1, serum levels of both TgAb and thyroid-stimulating hormone (TSH) were significantly increased. Obvious CD16 cell infiltration, IgG deposit and cleaved caspase-3 were observed in the thyroid of ENO1-immunized mice. Spatial learning and memory abilities and synaptic functions were impaired in ENO1-immunized mice. Furthermore, the expression levels of Iba-1, GFAP, interlukin-6, CDK5, and phosphorylated tau were increased, and endothelial tight junction proteins were decreased in the brain of ENO1-immunized mice. These results suggest that ENO1Ab can cause thyrocyte damage via ADCC effect and impair cerebral function by disrupting the blood-brain barrier.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.intimp.2020.106563DOI Listing
August 2020

Functional analysis of thyroid peroxidase gene mutations resulting in congenital hypothyroidism.

Clin Endocrinol (Oxf) 2020 10 8;93(4):499-507. Epub 2020 Jun 8.

Department of Endocrinology and Metabolism, Institute of Endocrine, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Hospital of China Medical University, Shenyang, China.

Objective: Thyroid peroxidase (TPO) is essential for thyroid hormone biosynthesis. TPO mutations might lead to congenital hypothyroidism. In the present study, we analysed the function of a compound heterozygous TPO mutation in a Chinese family.

Design: We studied a 23-year-old Chinese girl with a history of growth retardation and severe constipation from the age of 3 months, who was diagnosed as having congenital hypothyroidism.

Methods: Genomic DNA was extracted from peripheral blood samples obtained from the patient's family members. The genomic DNA was sequenced to detect mutations in a panel of genes associated with congenital hypothyroidism. Bioinformatic analysis and structural modelling predicted the potential disease-causing potential mutant genes and the microstructure of the mutant protein, respectively. Western blotting and ELISA were used to measure protein expression, and guaiacol oxidation assay measured the TPO activity of the mutant protein.

Results: We identified a compound heterozygous mutation (c.C1993T, c.T2473C) in the TPO gene. Bioinformatic analysis predicted that the TPO mutations were potentially disease causing. Structural modelling predicted damage to the microstructure of the mutant TPO protein. Western blotting and ELISA showed reduced protein levels of the mutant TPO protein compared with that of the wild-type protein. The mutant TPO protein showed weaker activity compared with that of the wild-type protein.

Conclusions: A novel compound heterozygous mutation of TPO gene was identified in a Chinese family. This mutation might alter the extracellular microstructure of TPO, and decrease its expression and the activity, resulting in congenital hypothyroidism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cen.14253DOI Listing
October 2020