Anaplastic thyroid cancer (ATC) is the most malignant thyroid cancer with a low incidence but high mortality. ATC is highly aggressive, rapidly progressing, and has poor prognosis. Current treatment options is not efficacious, so there is an urgent need to investigate its pathogenesis to update the treatment and improve the survival rate. Previous studies have found that most ATC can develop from well-differentiated thyroid cancer, and BRAF and RAS mutations are the key driving factors of ATC. TP53, PI3K pathway, PTEN, TERT, SWI/SNF complex Subunit, NF2 and other mutations also play an important role in the occurrence of ATC. Recent studies have found that single gene mutation is often not sufficient to drive the occurrence of ATC, and ATC is usually developed from the accumulation of multiple mutations in well-differentiated thyroid cancer. Therefore, this paper reviews the role of common combined mutations in ATC, deepens the understanding of the pathogenesis, and provides a basis for finding effective therapeutic targets.

Background: Developmental hypothyroidism impairs learning and memory in offspring, which depend on extensive neuronal circuits in the entorhinal cortex, together with the hippocampus and neocortex. The entorhinal-dentate gyrus pathway is the main entrance of memory circuits. We investigated whether developmental hypothyroidism impaired the morphological development of the entorhinal-dentate gyrus pathway. Methods: We examined the structure and function of the entorhinal-dentate gyrus pathway in response to developmental hypothyroidism induced using 2-mercapto-1-methylimidazole. Results: 1,1´-Dioctadecyl-3,3,3´,3´-tetramethylindocarbocyanine perchlorate tract tracing indicated that entorhinal axons showed delayed growth in reaching the outer molecular layer of the dentate gyrus at postnatal days 2 and 4 in hypothyroid conditions. The proportion of fibers in the outer molecular layer was significantly smaller in the hypothyroid group than in the euthyroid group at postnatal day 4. At postnatal day 10, the pathway showed a layer-specific distribution in the outer molecular layer, similar to the euthyroid group. However, the projected area of entorhinal axons was smaller in the hypothyroid group than in the euthyroid group. An electrophysiological examination showed that hypothyroidism impaired the long-term potentiation of the perforant and the cornu ammonis 3–cornu ammonis 1 pathways. Many repulsive axon guidance molecules were involved in the formation of the entorhinaldentate gyrus pathway. The hypothyroid group had higher levels of erythropoietin-producing hepatocyte ligand A3 and semaphorin 3A than the euthyroid group. Conclusion We demonstrated that developmental hypothyroidism might influence the development of the entorhinal-dentate gyrus pathway, contributing to impaired long-term potentiation. These findings improve our understanding of neural mechanisms for memory function.

Objective:To investigate the thyroid volume of adults in Lanzhou City, and analyze its influencing factors.Methods:In June 2016, according to the principle of multi-stage stratified cluster sampling, Han residents aged 18 and above in Chengguan, Xigu and Qilihe districts of Lanzhou City who had lived there for more than 5 years were selected as research subjects, and a portable B-ultrasound machine was used for thyroid examination. Morning urine samples of the subjects were collected to test urinary iodine; fasting venous blood samples of the subjects were collected to test serum thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), anti-thyroglobulin antibody (TgAb), blood lipids [triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL)] and blood uric acid (Ua) levels. At the same time, body indexes systolic blood pressure (SP), diastolic blood pressure (DP), waist circumference, height and weight were measured, and the body mass index (BMI) was calculated. Multiple linear regression was used to analyze the influencing factors of thyroid volume.Results:A total of 1 009 subjects were included, aged (43.50 ± 15.16) years, and the thyroid volume was (8.74 ± 3.39) ml. Among them, 534 males had a thyroid volume of (9.46 ± 3.43) ml; 475 females had a thyroid volume of (7.93 ± 3.15) ml, the thyroid volume of males was larger than that of females ( t = 7.36, P < 0.01). Thyroid volume was positively correlated with age, height, weight, BMI, SP, waist circumference, LDL, Ua and TgAb ( r = 0.07, 0.23, 0.33, 0.27, 0.10, 0.27, 0.10, 0.08, 0.07, P < 0.05), and it was negatively correlated with thyroid nodules, TPOAb, TSH and urinary iodine ( r = - 0.16, - 0.07, - 0.10, - 0.08, P < 0.05). After multiple linear regression analysis, TSH, TPOAb, TgAb and thyroid nodules were included in the regression equation, and the standardized B values were - 0.135, - 0.065, 0.123 and - 0.197, respectively. Conclusions:The thyroid volume of males is larger than that of females in Lanzhou City. TSH, TPOAb, TgAb and thyroid nodules are influencing factors of thyroid volume.

Thyroid cancer is highly heterogeneous and has three main types of histopathology: low-malignant papillary thyroid cancer, follicular cancer, and high-malignant undifferentiated cancer. It has recently been hypothesized that thyroid cancer stem cell (TCSC) plays a major role in both cancer initiation and metastasis, but the origin of TCSC and underlying mechanism in the development of thyroid cancer are still unclear. In this article, we introduced the origin theory of thyroid cancer from TCSC and the relation of TCSC to immune system and tumor microenvironment as well as TCSC-based treatment strategy. This will provide a new direction for the treatment of thyroid cancer, so as to improve the prognosis of patients with refractory thyroid cancer.

Thyroid hormone receptors are expressed in myocardium and vascular endothelial tissue and are very sensitive to changes in circulating thyroid hormone (TH) levels, especially triiodothyronine (T 3), therefore small changes can adversely affect the cardiovascular system. Evidence from several studies in recent years supports the association between abnormal thyroid function at the time of cardiovascular event and subsequent adverse cardiovascular outcomes. Several clinical trials have found that treatment of subclinical thyroid disease improves cardiovascular risk factors, suggesting the potential benefit of TH therapy in reducing cardiovascular outcome events. This article reviews the relationship between T 3 and cardiovascular disease and its physiological effects on the heart, as well as the therapeutic potential of T 3 in heart failure and acute myocardial infarction.

Hashimoto thyroiditis(HT) is a classic autoimmune thyroiditis (AIT), characterized by diffuse lymphocytic infiltration, destruction of thyroid structure, and positive autoantibodies. The pathogenesis of HT is complex and related to genetic susceptibility, immune system disorders, and environmental factors. The imbalance of T helper cell 1 (Th1)/ T helper cell 2 (Th2) is traditionally believed to be the main mechanism of HT. However, recent studies have shown that T helper cell 17 (Th17) plays an important role in the occurrence and development of HT through non-coding RNA regulation, autophagy-related pathway regulation, the balance with regulatory T cell (Treg). These mechanisms can enhance the release of inflammatory factors and aggravate HT by stimulating the differentiation of Th17, the inflammatory environment of HT also further stimulates the differentiation of Th17 and amplifies the inflammatory response. The regulatory mechanisms of Th17 are complex and have not yet been fully studied. Therefore, this article reviews the related mechanism of Th17 in HT to provide insights for novel therapeutic targets.

Objective:To compare the differences in clinicopathological characteristics between papillary thyroid microcarcinoma (PTMC) and papillary thyroid carcinoma (PTC) with a diameter≥2 cm.Methods:Clinicopathological and follow-up information of 1 404 PTC cases with diameter≤9 cm who received surgery and were confirmed pathologically from January 2010 to May 2017 in the First Hospital of China Medical University were analyzed retrospectively. All cases were divided into PTMC group and diameter ≥2 cm PTC group according to tumor diameter. The diameter of ≥2 cm PTC group was further categorized into two subgroups with 4 cm as the boundary. Clinical and pathological characteristics were analyzed. Meanwhile, risk factors that affected lymph node metastasis and postoperative recurrence of tumor were analyzed as well.Results:(1) A total of 1 404 eligible patients were included, consisting of 1 001 cases (71.3%) of PTMC and 403 cases (28.7%) of PTC of diameter≥2 cm with a median follow-up time of 43.00 (8.00-94.00) months. There were statistical differences in gender, age, serum thyroid stimulating hormone (TSH) level, bilobe, multifocality, cervical lymph node metastasis, extrathyroidal extension, body mass index, postoperative death, postoperative recurrence, and 131I treatment rate between two groups. Age, serum TSH level, bilobe, multifocality, cervical lymph node metastasis, extrathyroidal extension, postoperative recurrence, and 131I treatment rate were found statistically different among the PTMC group, 2 cm≤diameter≤4 cm PTC group, and 4 cm

Background: Subclinical hypothyroidism (SCH) is the most common thyroid dysfunction, and its relationship with blood pressure (BP) has been controversial. The aim of the study was to analyze the association between SCH and newly-diagnosed hypertension. Methods: Based on data from the Thyroid disease, Iodine nutrition and Diabetes Epidemiology (TIDE) study, 49,433 euthyroid individuals and 7,719 SCH patients aged ≥18 years were enrolled. Patients with a history of hypertension or thyroid disease were excluded. SCH was determined by manufacturer reference range. Overall hypertension and stage 1 and 2 hypertension were diagnosed according to the guidelines issued by the American College of Cardiology/American Heart Association in 2017. Results: The prevalence of overall hypertension (48.7%), including stage 1 (28.9%) and 2 (19.8%) hypertension, increased significantly in SCH patients compared with euthyroid subjects. With elevated serum thyroid stimulating hormone (TSH) level, the hypertension prevalence also increased significantly from the euthyroid to different SCH subgroups, which was more profound in females or subjects aged <65 years. The age- and sex-specific regression analysis further demonstrated the same trends in the general population and in the 1:1 propensity matched population. Similarly, several BP components (i.e., systolic, diastolic, and mean arterial BP) were positively associated with TSH elevation, and regression analysis also confirmed that all BP components were closely related with SCH in female subjects aged <65 years. Conclusion The prevalence of hypertension increases for patients with SCH. SCH tends to be associated with hypertension and BP components in females younger than 65 years.

Objective:To explore the reference interval of urinary iodine concentration(UIC)/urinary creatinine(UCr) ratio evaluating the iodine nutritional status in early pregnancy women.Methods:A reference interval of UIC/UCr ratio was determined among 5 609 early pregnant women with normal thyroid function, negative thyroid autoantibodies, and no history of diseases or taking drug that may affect thyroid function. Then we verified the reliability of this reference interval in a group of 7 514 women in early pregnancy.Results:We determined the UIC/UCr ratio of 75-149 μg/g as the reference interval. In the reference interval, thyroglobulin antibody(TgAb), thyroid peroxidase antibody(TPOAb), and thyroglobulin(Tg) were all at lower levels, and the overall distributions were approximately U-shaped. The prevalence of thyroid dysfunction, the positive rates of antibodies and the proportion of Tg>40 μg/L were the lowest within the reference interval, while higher on both sides of the interval.Conclusion:The reasonable reference interval of the UIC/UCr ratio in iodine-sufficient regions is 75-149 μg/g in early pregnerty women.

Background: Subclinical hypothyroidism (SCH) is the most common thyroid dysfunction, and its relationship with blood pressure (BP) has been controversial. The aim of the study was to analyze the association between SCH and newly-diagnosed hypertension. Methods: Based on data from the Thyroid disease, Iodine nutrition and Diabetes Epidemiology (TIDE) study, 49,433 euthyroid individuals and 7,719 SCH patients aged ≥18 years were enrolled. Patients with a history of hypertension or thyroid disease were excluded. SCH was determined by manufacturer reference range. Overall hypertension and stage 1 and 2 hypertension were diagnosed according to the guidelines issued by the American College of Cardiology/American Heart Association in 2017. Results: The prevalence of overall hypertension (48.7%), including stage 1 (28.9%) and 2 (19.8%) hypertension, increased significantly in SCH patients compared with euthyroid subjects. With elevated serum thyroid stimulating hormone (TSH) level, the hypertension prevalence also increased significantly from the euthyroid to different SCH subgroups, which was more profound in females or subjects aged <65 years. The age- and sex-specific regression analysis further demonstrated the same trends in the general population and in the 1:1 propensity matched population. Similarly, several BP components (i.e., systolic, diastolic, and mean arterial BP) were positively associated with TSH elevation, and regression analysis also confirmed that all BP components were closely related with SCH in female subjects aged <65 years. Conclusion The prevalence of hypertension increases for patients with SCH. SCH tends to be associated with hypertension and BP components in females younger than 65 years.