The expression of the Dickkopf homolog 3 (DKK3) gene is downregulated in some human cancers, suggesting a possible tumor suppressor role of this gene. The role and regulation of DKK3 in thyroid cancer have not been examined. In this study, we explored the relationship of promoter methylation with the inactivation of DKK3 and tumor behaviors in papillary thyroid carcinoma (PTC). We used methylation-specific PCR and RT-PCR to examine the promoter methylation and expression of DKK3 and tumor characteristics. We found mRNA expression of DKK3 in 44.9% of the PTC tissue samples vs 100% of the matched normal thyroid tissue samples (P!0.01). In contrast, an opposite distribution pattern of DKK3 gene methylation was observed; specifically, 38.8% of the PTC tissue samples vs 0% of the matched normal thyroid tissue samples harbored DKK3 methylation. An inverse correlation between the promoter methylation and mRNA expression of DKK3 in PTC tissue samples was also observed. Moreover, we also found an inverse correlation between DKK3 expression and some aggressive pathological characteristics of PTC, including high TNM stages and lymph node metastasis, but a positive correlation between DKK3 promoter hypermethylation and pathological aggressiveness of the tumor. Treatment of the PTC cell line TPC-1 with the demethylating agent 5-azaC reduced DKK3 promoter methylation and enhanced its expression, establishing functionally the impact of DKK3 methylation on its expression. Our data thus for the first time demonstrate that the DKK3 gene is a potential tumor suppressor gene in thyroid cancer and that aberrant promoter methylation is an important mechanism for its downregulation, which may play a role in the tumorigenesis and aggressiveness of PTC.

Thyroid cancer is an endocrine malignancy with a high incidence rate, which is affected by female hormones, particularly estrogens, in its growth and progression. IQ-domain GTPase-activating protein 1 (IQGAP1) is overexpressed in a range of types of cancer and is reported to interact with estrogen receptor α (ERα) in breast cancer cells. However, the association between IQGAP1 and ERα in thyroid cancer cells remains to be elucidated. In this study, the role of IQGAP1 in thyroid cancer cells was examined. The expression of IQGAP1 (190 kDa) was analyzed using western blot analysis, which indicated that IQGAP1 was overexpressed in thyroid cancer tissues and FTC133 cells. However, IQGAP1 knockdown in the FTC133 cells led to a significant downregulation in ERα transcriptional activity, cell proliferation, cell adhesion and cell invasion under 17β-estradiol (E2) conditions. Furthermore, ERα knockdown inhibited the enhanced protein expression levels of phosphorylated ERK1/2 and cyclin D1, which were induced by the overexpression of IQGAP1. Co-immunoprecipitation was also performed in thyroid cancer cells and the results suggested that IQGAP1 directly interacted with ERα in the FTC133 cells and the co-transfected COS-7 cells. Taken together, these findings revealed that IQGAP1 may directly interact with ERα and serve as a signal integrator, mediating ERα transcriptional activity, cell proliferation and cell invasion during the progression of thyroid cancer.

Diabetic ketoacidosis (DKA) and thyroid storm (TS) are severe metabolic and endocrine disorders. Both usually manifest with multiple systemic clinical signs and symptoms, and digestive symptoms, such as nausea and vomiting, are most common in these patients. Moreover, the presence of a concurrent severe or rare complication may worsen the condition or even cause death due to misdiagnosis, delayed diagnosis, or inappropriate treatment. The identification of these symptoms is usually closely related to the severity and prognosis of the disease. Although clinical prognosis might be improved by prompt diagnosis and aggressive treatment, some rare and insidious metabolic complications are difficult to identify early. Moreover, life-threatening gastrointestinal symptoms are very rare in patients with DKA and TS. Here, we report an inpatient diagnosed with DKA and Graves’ disease who developed life-threatening intractable hiccups resulting in TS and respiratory failure during the treatment of DKA. In addition, we review the literature to discuss the possible underlying mechanism of intractable hiccups in the development of TS.

Objective. To investigate the cause of misdiagnosis and the diagnosis and treatment of tuberculosis of thyroid. Methods. Four cases of tuberculosis of thyroid were reported and the related literature was reviewed, as well as the causes of misdiagnosis and the diagnosis and treatment were discussed. Results. Two cases were misdiagnosis as thyroid adenoma and one case as thyroid carcinoma, while one case as missed diagnosis. Part of resection, local excision, and lobectomy was performed, respectively, with all the patients who were treated with antituberculosis drugs and recovered. Conclusion. The atypical manifestation of tuberculosis of thyroid suggested that it is important to reinforce the knowledge of this disease. Cytological examination by fine-needle aspirate biopsy was helpful to the diagnosis. The first choice was treatment with anti-tuberculosis drugs.

Objective. To explore the application value of N-terminal pro-B type natriuretic peptide (NT-proBNP) combined with neutrophil-to-lymphocyte ratio (NLR) in evaluation of major adverse cardiac events (MACEs) in elderly patients with chronic heart failure (CHF). Methods. 50 CHF patients admitted to the Department of Cardiovascular Medicine of our hospital from January 2021 to December 2021 were selected as the observation group. Another 50 non-CHF patients of our hospital were selected as the control group. Clinical data were collected from subjects who met the inclusion criteria, including general information, personal disease history, and laboratory test indicators. Patients with CHF were followed up for 6 months. Patients with CHF were divided into two groups, MACE group and non-MACE group. Results. The levels of WBC, NEU, NLR, and NT-proBNP in observation group were higher than those in control group, but the level of LYM was the opposite ( P < 0.05 ). The age, WBC, NEU, LYM, PLT, blood glucose, NLR, and NT-proBNP of MACE group and non-MACE group were significantly different ( P < 0.05 ). The increased levels of NEU, NLR, NT-proBNP and the decreased levels of LYM and PLT are all independent risk factors for MACE in elderly patients with CHF ( P < 0.05 ). The AUC of NLR in evaluating the occurrence of MACE in elderly CHF patients was 0.841. When the Youden index was 0.7692, the sensitivity was 76.92% and the specificity was 100.00%. The AUC of NT-proBNP in evaluating the occurrence of MACE in elderly CHF patients was 0.705. When the Youden index was 0.5260, the sensitivity was 76.92% and the specificity was 75.68%. The AUC of NT-proBNP combined with NLR in evaluating the occurrence of MACE in elderly CHF patients was 0.954. When the Youden index was 0.8420, the sensitivity was 92.31% and the specificity was 91.89%. Conclusion. NT-proBNP combined with NLR has high value in the evaluation of MACE in elderly CHF patients and can be used as an auxiliary predictive index in clinic.