[Recognise of iodine effect on thyroid diseases and metabolism].

Iodine is an essential trace element for human and an antioxidant. It not only participates in the synthesis of thyroid hormone, but also plays a role in metabolic diseases. Previous studies mainly focused on the effect of iodine on thyroid diseases, but ignored the effect on metabolism. After the implementation of the universal salt iodization (USI) of China, the possible consequences of excessive iodine were emphasized while the harm of iodine deficiency was forgetten. The paper re-examines the effects of iodine nutrition on thyroid diseases and metabolism. Iodine deficiency can lead to an increased risk of iodine deficiency disorders and thyroid diseases, and increase prevalence of metabolic syndrome and its components. Moderate iodine excess is beneficial to metabolism, but it can increase the risk of hyperthyroidism and subclinical hypothyroidism. The average urinary iodine concentration in 100-299 µg/L is the appropriate iodine nutrition state. According to the present iodized content of salt in China, iodized salt is an economical and effective way to ensure adequate iodine nutrition.

[Survey on the prevalence and related factors of thyroid disorders in different iodine intake regions in China in 2015-2017].

Objective: To observe the prevalence and related factors of thyroid diseases in different iodine intake areas from 2015 to 2017 after the implementation of national salt iodization policy in China for 20 years. Methods: A cross-sectional survey. Multi-stage stratified cluster random sampling was used to randomly select subjects meeting the inclusion criteria from 31 provinces, municipalities and autonomous regions in China from January 2015 to December 2017, and stratified by age and sex. The survey included questionnaire, physical examination and thyroid ultrasonography. At the same time, the concentrations of serum thyrotropin, thyroxine, thyroid peroxidase antibody (TPOAb), thyroid globulin antibody (TgAb) and urinary iodine were measured.To determine whether the patient has a certain thyroid disease according to the above results. Different iodine nutrition areas were defined according to urinary iodine concentration, and the influence of iodine nutrition status in different iodine intake areas on thyroid diseases was analyzed. Results: A total of 78 470 adults were included, including 39 893 in the area of moderate iodine, 28 779 in the area of adequate iodine, and 9 798 in the area of excessive iodine.In the above three regions, the prevalence of subclinical hyperthyroidism (hyperthyroidism) was 0.45% (95%CI: 0.39%-0.52%), 0.50%(95%CI: 0.35%-0.70%)and 0.27%(95%CI: 0.20%-0.35%), respectively, with statistical significance(χ²=6.92, P=0.003). The prevalence of subclinical hypothyroidism (hypothyroidism) was 11.36% (95%CI: 10.73%-12.02%), 13.57%(95%CI: 11.70%-15.69%) and 16.18%(95%CI: 12.41%-20.82%), respectively, with statistical significance(χ²=5.08, P=0.009). The prevalence rates of Graves' disease, TPOAb, goiter and thyroid nodule among the three regions were statistically significant (all P<0.05). There were no significant differences in the prevalence of clinical hyperthyroidism and clinical hypothyroidism and the positive rate of TgAb among the three regions (all P>0.05). Multivariate logistic regression model analysis showed that excess iodine was a risk factor for subclinical hypothyroidism (OR=1.24, 95%CI: 1.06-1.44), and a protective factor for thyroid nodules (OR=0.73, 95%CI: 0.57-0.94). Iodine overdose was a risk factor for subclinical hypothyroidism (OR=1.47, 95%CI: 1.08-2.01), while it was a protective factor for subclinical hyperthyroidism (OR=0.56, 95%CI: 0.41-0.77), and TPOAb positive (OR=0.93, 95%CI: 0.87-0.99), goiter (OR=0.33, 95%CI: 0.17-0.66) and thyroid nodule (OR=0.77, 95%CI: 0.61-0.97). Conclusions: There are significant differences in the prevalence of subclinical hyperthyroidism, subclinical hypothyroidism, positive TPOAb, thyroid nodule and goiter in different iodine intake regions. Different iodine intake levels have an effect on the incidence of thyroid diseases.

[Efficacy and safety of Changsulin® compared with Lantus® in type 2 diabetes: a phase â ¢ multicenter, randomized, open-label, parallel, controlled clinical trial].

Objective: To compare the efficacy and safety of Changsulin® with Lantus® in treating patients with type 2 diabetes mellitus (T2DM). Methods: This was a phase Ⅲ, multicenter, randomized, open-label, parallel-group, active-controlled clinical trial. A total of 578 participants with T2DM inadequately controlled on oral hypoglycemic agents were randomized 3∶1 to Changsulin® or Lantus® treatment for 24 weeks. The efficacy measures included changes in glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), 2h postprandial plasma glucose (2hPG), 8-point self-monitoring of blood glucose (SMBG) profiles from baseline, and proportions of subjects achieving targets of HbA1c and FPG. The safety outcomes included rates of hypoglycemia, adverse events (AEs) and anti-insulin glargine antibody. Results: After 24 weeks of treatment, mean HbAlc decreased 1.16% and 1.25%, FPG decreased 3.05 mmol/L and 2.90 mmol/L, 2hPG decreased 2.49 mmol/L and 2.38 mmol/L in Changsulin® and in Lantus®, respectively. No significant differences could be viewed in above parameters between the two groups (all P>0.05). There were also no significant differences between Changsulin® and Lantus® in 8-point SMBG profiles from baseline and proportions of subjects achieving the targets of HbA1c and FPG (all P>0.05). The rates of total hypoglycemia (38.00% and 39.01% for Changsulin® and Lantus®, respectively) and nocturnal hypoglycemia (17.25% and 16.31% for Changsulin® and Lantus®, respectively) were similar between the two groups (all P>0.05). Most of the hypoglycemia events were asymptomatic, and no severe hypoglycemia were found in both groups. No differences were observed in rates of AEs (61.77% vs.52.48%) and anti-insulin glargine antibody (after 24 weeks of treatment, 6.91% vs.3.65%) between the two groups (all P>0.05). Conclusions: Changsulin® shows similar efficacy and safety profiles compared with Lantus® and Changsulin® treatment was well tolerated in patients with T2DM.

Meta-analysis of ART outcomes in women with different preconception TSH levels.

BACKGROUND: To assess whether elevated thyroid-stimulating hormone (TSH) levels before conception can predict poor outcomes of assisted reproductive technology (ART). METHODS: Prior to July 2018, we searched the PubMed, EMBASE, COCHRANE, Google Scholar, and CNKI databases for studies. Retrospective or prospective reports that compared ART results in patients with subclinical hypothyroidism (SCH) with normal thyroid function were selected. Two reviewers separately reviewed each potential article for qualification, analyzed the quality of the studies according to the Newcastle-Ottawa scale, and extracted the data. The PRISMA guidelines were adopted. RESULTS: We selected a total of 18 publications that included 14,846 participants for this meta-analysis. When the TSH cut-off value for SCH was set at 2.5 mIU/L, no significant differences were observed in ART-related outcomes between SCH patients and normal women. The evaluated outcomes included the live birth rate (LBR) (OR: 0.93; 95% CI (0.77,1.12), P = 0.43), clinical pregnancy rate (CPR) (OR:1.02; 95% CI (0.90,1.17); P = 0.74), pregnancy rate (PR) (OR: 1.00; 95% CI (0.89,1.12); P = 0.99), and miscarriage rate (MR) (OR:1.24; 95% CI (0.85, 1.80); P = 0.26). Furthermore, when a higher TSH level was used as the cut-off value to diagnose SCH (i.e., 3.5-5 mIU/L), a significant difference was found in the MR (OR: 1.91; 95% CI (1.09, 3.35); P = 0.02) between the two groups of ART-treated women. However, when a broader cut-off value was used to define SCH, no significant differences were observed in the LBR (OR: 0.72; 95% CI (0.47,1.11); P = 0.14), CPR (OR: 0.82; 95% CI (0.66,1.00); P = 0.052), or PR (OR: 1.07; 95% CI (0.72,1.60); P = 0.74) between the two groups of ART-treated women. CONCLUSION: No difference was observed in ART outcomes when a TSH cut-off value of 2.5 mIU/L was used. However, when a broader TSH cut-off value was used, preconception SCH resulted in a higher miscarriage rate than in normal women.

Subclinical hypothyroidism and depression: a meta-analysis.

The objective of this study was to evaluate the relationship between subclinical hypothyroidism (SCH) and depression. We also analysed the effect of levothyroxine (L-T4) on depression in SCH patients. We found an insignificant difference for the composite endpoint: standard mean difference (SMD) of 0.23 (95% confidence interval (CI) -0.03, 0.48, P = 0.08, I2 = 73.6%). The odds ratio (OR) for depressive patients was 1.75 (95% CI 0.97, 3.17 P = 0.064, I2 = 64.6%). Furthermore, sub-group analysis according to age found that SCH was related to depression in younger patients (<60 years old), as defined by the diagnosis of depression: OR of 3.8 (95% CI 1.02, 14.18, P = 0.047, I2 = 0.0%) or an increase on the depressive scale: SMD of 0.42 (95% CI 0.03, 0.82, P = 0.036, I2 = 66.6%). Meanwhile, SCH did not associate with depression in older patients (≥60 years old), as defined by the diagnosis of depression: OR of 1.53 (95% CI 0.81, 2.90, P = 0.193, I2 = 71.3%) or an increase on the depressive scale: SMD of 0.03 (95%CI -0.31, 0.37, P = 0.857, I2 = 79.8%). We also found an insignificant difference in the composite endpoint between the L-T4 supplementation group and placebo group in SCH patients. The estimated SMD was 0.26 (95% CI -0.09, 0.62, P = 0.143, I2 = 52.9%). This meta-analysis demonstrates that SCH is not connected to depression. However, sub-group analysis according to age found that SCH is related to depression in younger patients, but not in older patients. Furthermore, we failed to find an effect of L-T4 supplementation treatment for SCH on depression.

Clinical and genetic analyses of Chinese patients with Gitelman syndrome.

To evaluate the genotype-phenotype relationship of Gitelman syndrome in Chinese patients. We selected patients with Gitelman syndrome presenting hypokalemia. Medical history, clinical manifestations, laboratory test results, and imaging data of these patients were collected for analysis. Target gene sequencing was performed to evaluate the genotype-phenotype relationship. Gitelman syndrome was diagnosed based on medical history, clinical manifestations, laboratory test results, and imaging data. The causative gene for Gitelman syndrome, SLC12A3, and the causative gene for the classic Bartter syndrome, CLCNKB, were screened for disease-causing mutations by direct sequencing. Clinical diagnoses of ten patients were consistent with Gitelman syndrome. Disease-causing mutations in the SLC12A3 gene were found in six patients. Among the variants, T60M in exon 1 was the hot spot in Chinese patients. Additionally, we found a small deletion of ACGG in exon 3 and L671P in exon 16; these have not been reported in previous studies. No disease-causing mutations were observed in the other four patients. Since mutations in the SLC12A3 and CLCNKB genes are not present in all patients with clinical manifestations of Gitelman syndrome, genetic screening after clinical diagnosis is essential.

A female patient with normosmic idiopathic hypogonadotropic hypogonadism carrying a novel mutation in FGFR1.

Mutations in the fibroblast growth factor receptor 1 gene (FGFR1) have been reported in patients with Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism (nIHH). Here, we report an nIHH patient with a novel mutation in FGFR1. The patient was a 19-year-old female who presented the nIHH phenotype with primary amenorrhea, cleft lip and palate, mixed hearing disorders, and skeletal malformations. Coding regions of 12 genes that have been implicated in nIHH were analyzed by direct sequencing. Mutation analysis revealed a novel mutation at exon 10 of the FGFR1 gene, 1422 C>G, and a C→G transition in codon 476, which resulted in the replacement of aspartic acid with glutamic acid. The patient's family members did not possess this mutation. We briefly reviewed FGFR1 variants found in Chinese subjects. These results indicate that the mutation in FGFR1 is a cause of nIHH, which is associated with specific non-reproductive phenotypes.

Effects of maternal subclinical hypothyroidism on obstetrical outcomes during early pregnancy.

BACKGROUND: Maternal hypothyroidism [overt hypothyroidism and subclinical hypothyroidism (SCH)] during early pregnancy is suspected to associate with adverse obstetrical outcomes. AIM: The aim of the present study was to investigate whether maternal SCH during the early stage of pregnancy increase obstetrical complications and whether treatment results in an improvement in these outcomes. SUBJECTS AND METHODS: A total of 756 women in the 1st trimester (≤12 weeks) of pregnancy were enrolled through 10 hospitals in Shenyang from 2007 to 2009. All participants underwent thyroid function testing in early pregnancy and their obstetrical outcomes were studied following delivery. RESULTS: The incidence of spontaneous abortions in the SCH group was higher than the normal TSH group (15.48% vs 8.86%, p=0.03). No significant association was observed between SCH and other obstetrical complications including gestational hypertension, premature delivery, anemia, post-partum hemorrhage, low neonatal Apgar scores and low birth weight. Although levo-T4 (L-T4) treatment decreased the incidence of spontaneous abortions in women with SCH, it was not statistically significant when compared to women who did not receive treatment in the SCH group. None of the 28 women who received L-T4 treatment had premature delivery, low birth weight, hemorrhage, and low Apgar score. CONCLUSIONS: The incidence of spontaneous abortion in pregnant women with SCH increases in early pregnancy.

Expression of GDF-9, BMP-15 and their receptors in mammalian ovary follicles.

The synergetic process of folliculogenesis is mainly regulated by GDF-9 and BMP-15 as well as their receptors, such as BMPR2, TßR1 and BMPR1B. Expressions of these factors and the receptors are significant different among species. This study was designed to detect expression of GDF-9, BMP-15 and their receptors in mouse, porcine and human healthy follicles by immunohistochemistry. Three ages of human ovary were studied according to ovarian developmental schedule, i.e. gestational week (GW) 16, puberty (14 year-old) and adult (40 year-old). The results showed that both GDF-9 and BMP-15 were detectable in oocytes from primary follicles onward, besides, BMP-15 also presented in granulosa cells (GCs) and follicular follicle of mature follicles in mouse. However, they were maintained in oocytes and GCs from primordial to mature follicles in porcine except that GDF-9 was undetectable in GCs of mature follicles. For human ovary, GDF-9 presented in oocytes of primordial follicles in all samples, whereas BMP-15 was only observed in primordial follicle of adult ovary. Receptors, BMPR2, TßR1 and BMPR1B were found in oocytes and GCs of all follicles in mouse and porcine. In human, they were stained in oocytes from primordial follices but BMPR1B was not expressed in pubertal primordial follicles. Furthermore, we found that GDF-9, BMP-15 and three receptors distributed in adult corpus lutea. Collectively, our studies suggested that GDF-9, BMP-15 and their receptors might correlate with primordial follicular recruitment in pig and human. Positive expression of the receptors (BMPR2, TßR1 and BMPR1B)in primordial follicles of mouse ovaries indicated that these receptors might interact with others ligands besides GDF-9 and BMP-15 to regulate primordial follicular activity in mouse. Moreover, presence of GDF-9 in oocytes and BMP-15 in oocytes and GCs of mature follicles from mice and porcine elucidated coordinated roles of GDF-9 and BMP-15 in cumulus oophorus expansion. Additionally, expression of these factors in adult human corpus lutea suggested they play roles in corpus luteum activity.

A study for maternal thyroid hormone deficiency during the first half of pregnancy in China.

BACKGROUND: Maternal thyroid hormone deficiency is the most common disorder of thyroid function during pregnancy and can influence the outcome for mother and foetus. The purpose of this study was to investigate the prevalence of thyroid hormone deficiency during the first half of pregnancy in iodine sufficient areas of China. MATERIALS AND METHODS: Four thousand eight hundred pregnant women from 10 hospitals during the first 20 weeks of gestation were enrolled in this study. All sera obtained from pregnant women were measured for thyrotropin, free thyroxine and thyroid peroxidase antibody. Screening for thyroid hormone deficiency was performed on pregnant women using gestational age-specific reference intervals or non-pregnant population reference intervals. RESULTS: With gestational age-specific reference intervals as the criterion, the prevalence of subclinical hypothyroidism at 4, 8, 12,16 and 20 weeks of gestation was 4.59%, 6.15%, 4.68%, 4.53% and 5.96%, respectively, and the prevalence of hypothyroxinaemia was 3.69%, 1.11%, 2.92%, 1.29% and 2.29%, respectively. Different prevalence was obtained when non-pregnant population reference intervals was used as the criterion. If non-pregnant population reference intervals were used, the percentage of potentially misclassified cases of subclinical hypothyroidism were 0.18%, 2.85%, 4.1%, 3.24%, and 3.21%, respectively, and 3.45%, 0.66%, 2.34%, 1.29%, and 1.83%, respectively, in potentially misclassified cases of hypothyroxinaemia. CONCLUSIONS: The percentage of potentially misclassified cases of subclinical hypothyroidism and hypothyroxinaemia in pregnant women decreased by using the gestational age-specific reference intervals as a diagnostic criteria during the first half of pregnancy.

Exercise therapy of non-insulin dependent diabetes mellitus. Effects of acute exercise loading.

The dynamic changes of 15 parameters (divided into 6 sections in this study) relating to metabolism, platelet function, blood coagulation and hemorrheologic situation under acute exercise loading with the intensity of VO2 max 60% were observed in noninsulin dependent diabetes mellitus (NIDDM) patients. The advantage, safety and feasibility of exercise therapy were discussed.

[Study of LDL receptor activity of lymphocyte by immunofluorescence method].

Fluorescein-isothiocyanate (FITC) labeled anti-LDL-IgG was used to demonstrate LDL bound with lymphocytes. The activity of LDL receptor was expressed by the fluorescence intensity of individual cell (receptor-ligand immunofluorescence method). With this method the effect of dietary cholesterol on LDL receptor activity of lymphocytes was studied. The results showed that with the elevation of plasma cholesterol, the fluorescence intensity of individual cell and the percentage of labelled cell were decreased. i.e. the LDL receptor activity was reduced due to hypercholesterolemia, and lowering of plasma cholesterol level might be accompanied with restoration of the LDL receptor activity. These results suggest that inhibition of LDL receptor activity in patients with non-familial hypercholesterolemia can be recovered by decreasing plasma cholesterol level.

[Effects of verapamil on pulmonary arterial pressure in patients with cor pulmonale complicated by heart failure].

In this study, observation of the effects of verapamil on pulmonary arterial pressure and on treating right heart failure were done in 15 patients with chronic cor pulmonale complicated with heart failure using monitoring of hemodynamic changes by right cardiac catheter. The results showed that verapamil had remarkable effect on pulmonary arterial pressure. With no significant effect on systemic blood pressure, verapamil decreases right ventricular systolic pressure by 1.3 kPa (9.6 mmHg), pulmonary arterial systolic pressure by 1.5 kPa (11 mmHg) and mean pulmonary arterial pressure by 1.1 kPa (8.5 mmHg). Verapamil is clinically useful by decreasing cardiac afterload, improving cardiac function, treating right heart failure and relieving bronchial spasm.