Causal association of TSH with ischemic heart diseases and heart failure: A 2-sample Mendelian randomization study.

Thyroid dysfunction is associated with the risk of cardiovascular disease; however, whether plasma thyroid-stimulating hormone (TSH) levels in subjects with euthyroidism affect the risk of cardiovascular disease remains unclear. This study aimed to investigate the causal association between plasma TSH levels and cardiovascular diseases, particularly ischemic heart disease and heart failure (HF). Summary statistics from the Integrative Epidemiology Unit Open genome-wide association studies Project and FinnGen consortium were used to investigate the causal relationship between plasma TSH levels and the risk of cardiovascular diseases. Two-sample Mendelian randomization analysis using inverse-variance weighting as the primary method was performed. The MR Pleiotropy RESidual Sum and Outlier and leave-one-out methods were used to ensure the robustness of our findings. Genetically determined plasma TSH levels were associated with major coronary heart disease events (OR 1.0557, 95% CI 1.0141-1.0991), all-cause HF (OR 0.9587, 95% CI 0.9231-0.9956), and HF + non-ischemic cardiomyopathy (OR 0.9318, 95% CI 0.8786-0.9882). After the Bonferroni correction, the causation described above disappeared. In the secondary analysis, genetically determined higher TSH levels were associated with a higher risk for unstable angina pectoris (OR 1.0913, 95% CI 1.0350-1.1507), but were associated with a lower risk for HF + overweight (OR 0.9265, 95% CI 0.8821-0.9731). These results were further validated using sensitivity analysis. Our findings show that increased plasma TSH levels in patients with euthyroidism may increase the risk of unstable angina pectoris but reduce the risk of HF in overweight patients. This evidence indicates that plasma TSH levels may need to be carefully controlled in specific patients.

Incidence and risk factors for occult lesions in low-risk papillary thyroid microcarcinoma patients with tumor characteristics appropriate for thermal ablation: A retrospective study.

In recent years, thermal ablation has been increasingly employed for the treatment of low-risk papillary thyroid microcarcinoma (PTMC) across various institutions. Its use as a standard or initial treatment continues to be a subject of debate. Retrospective analyses of the surgical pathology in post-ablation patients have indicated that occult lesions are not uncommon. This retrospective study aimed to examine the incidence and risk factors of occult lesions via postoperative pathology in low-risk PTMC patients who fulfilled the criteria for thermal ablation therapy. We examined the medical records of patients who underwent thyroid surgery and had a Bethesda classification V or VI based on fine needle aspiration cytology between November 22, 2020, and December 31, 2022. A total of 413 patients with preoperative tumor characteristics appropriate for thermal ablation were included in this study. Occult lesions, encompassing ipsilateral or contralateral occult carcinoma or central lymph node metastases may have occurred in 34.7% of patients. Male gender (OR: 2.526, 95% CI: 1.521-4.195, P = .000), tumor location in the lower pole (OR: 1.969, 95% CI: 1.186-3.267, P = .009), multiple microcalcifications (OR: 5.620, 95% CI: 2.837-11.134, P = .000), and Hashimoto's thyroiditis (OR: 2.245, 95% CI: 1.292-3.899, P = .004) were independent risk factors for the presence of occult lesions. In low-risk PTMC patients exhibiting tumor characteristics amenable to thermal ablation, over one-third of the patients may present with occult lesions. Meticulous evaluation of the presence of additional lesions is necessary before performing thermal ablation, particularly in patients exhibiting high-risk factors for occult lesions.

SKA3 Promotes Cell Growth in Breast Cancer by Inhibiting PLK-1 Protein Degradation.

Breast cancer (Bca) remains the most common form of malignancy affecting females in China, leading to significant reductions in the mental and physical health of those with this condition. While spindle and kinetochore associated complex subunit 3 (SKA3) is known to be linked with cervical cancer progression, whether it is similarly associated with Bca progression remains unknown. Using shRNA, we specifically knocked down the expression of SKA3 in Bca cell lines and then assessed the resultant changes in cell proliferation using CCK-8 and colony formation assays. In addition, we used western blotting to quantify the expression levels of relevant proteins in these cells, and we assessed the interaction between SKA3 and polo-like kinase-1 (PLK-1) via co-immunoprecipitation.In this study, we observed elevated SKA3 expression in Bca tissues and cell lines. When we knocked down SKA3 expression in Bca cells, we were able to determine that it functions in an oncogenic manner so as to promote the growth and proliferation of these cells in vitro. From a mechanistic perspective, we were able to show that in Bca cells SKA functions at least in part via interacting with PLK-1 and preventing its degradation. In summary, we found that SKA3 is able to regulate PLK-1 degradation in Bca cells, thus controlling their growth and proliferation. These results highlight SKA3 as a potentially viable target for anti-cancer drug development aimed at combatting Bca.

Plasma ω-3 and ω-6 fatty acids in thyroid diseases.

The incidences of nodular goiter (NG), thyroid adenoma (TA), and thyroid cancer (TC) are increasing rapidly; however, the etiologies of these diseases remain unclear. The present study aimed to evaluate the differences in plasma fatty acids among these three thyroid diseases to facilitate etiological research. Four ω-3 and seven ω-6 polyunsaturated fatty acids were measured from 97 TC, 14 TA and 11 NG patient plasma samples with gas chromatography-flame ionization detector. Fatty acids levels were expressed as the percentage of each fatty acid out of the total fatty acids evaluated. The present study identified that the level of 22:6n-3 [median, interquartile range (IQR)] was significantly increased in TA (5.2%, 4.3-6.4%) compared with NG (3.6%, 3.1-4.6%) and TC patients (4.2%, 3.2-4.8%). Though not statistically significant, the levels of 20:5n-3 and 22:5n-3 demonstrated a similar pattern. The level of 22:4n-6 expressed (median, IQR) was significantly increased in NG patients (0.21%, 0.18-0.26%) compared with TA (0.16%, 0.15-0.18%) and TC (0.17%, 0.14-0.22%) patients. Furthermore the fatty acids 18:3n-6, 20:2n-6, 20:3n-6, 20:4:6, and 22:5n-6 demonstrated a similar but statistically insignificant pattern. This suggests that different fatty acids exhibit various etiological roles in NG, TA and TC and warrant further study.

BRAFV600E mutation is not associated with central lymph node metastasis in all patients with papillary thyroid cancer: Different histological subtypes and preoperative lymph node status should be taken into account.

The association between central lymph node metastasis (LNM) and risk factors, including the presence of the BRAF mutation, BRAFV600E, in patients with papillary thyroid cancer (PTC) requires further investigation. A potent risk factor that can indicate LNM in different histological subtypes of PTC and in different preoperative central lymph node statuses also requires further research. A total of 287 patients with PTC who accepted thyroidectomy were included in the present study. Clinicopathological data of these patients were reviewed to examine the risk factors for central LNM through univariate and multivariate analyses. Overall, BRAFV600E in patients with cN0 (subclinical nodal disease) and cN1 (other than cN0) PTC was associated with central LNM. However, multivariate analyses demonstrated that BRAFV600E was not an independent risk factor in patients with cN1 or cN0 PTC. For patients with classical variant PTC (CVPTC), BRAFV600E was independently associated with central LNM. However, on further analysis, the association was only significant in patients with cN0 CVPTC. For patients with follicular variant PTC (FVPTC) or aggressive variant PTC (AVPTC), the BRAFV600E mutation rate was not significantly different between patients with and without central LNM. In conclusion, BRAFV600E was an independent risk factor for central LNM overall in patients with PTC and in patients with CVPTC, particularly in patients with cN0 CVPTC. However, BRAFV600E was not an independent risk factor for patients with FVPTC and AVPTC. Therefore, BRAFV600E provides varied clinical significance in different histological subtypes and preoperative central lymph node status.

Correlation between serum lead and thyroid diseases: papillary thyroid carcinoma, nodular goiter, and thyroid adenoma.

Studies have showed that lead was associated with human health. However, the effects of lead on thyroid functions are inconsistent, and studies based on Chinese population are fragmentary. To evaluate the correlation between lead and thyroid functions of Chinese with different thyroid diseases, we conducted a hospital-based study. Ninety-six papillary thyroid carcinoma (PTC), 10 nodular goiter (NG), and 7 thyroid adenoma (TA) patients were recruited from the First Affiliated Hospital of Wenzhou Medical University, China. Serum triiodothyronine (T3), free triiodothyronine (FT3), free thyroxin (FT4), and thyroid stimulating hormone (TSH) were evaluated with chemiluminescent microparticle immunoassay. Serum lead was assessed with ICP-MASS. Partial correlation was used to explore the correlations of serum lead and thyroid diseases. Compared to PTC, the level of lead was significantly higher in TA, and lower in NG (p < 0.05). This difference remained significant in females when stratified by sex. Serum lead was negatively correlated with TSH (rs =  - 0.27, p < 0.05) in PTC group. T3 was positively related to lead at quartile4 (rs = 0.61, p < 0.05) in PTC group. No significant correlations were observed between lead and FT3 or FT4 in any group. The results suggested that lead might have different etiological roles in these three thyroid diseases.

BRAF and TERT promoter mutations in the aggressiveness of papillary thyroid carcinoma: a study of 653 patients.

The role of telomerase reverse transcriptase (TERT) gene promoter mutations in the aggressiveness of papillary thyroid cancer (PTC) remains to be further investigated. Here we examined the relationship of TERT promoter mutations and BRAF V600E with the clinicopathological features of PTC in 653 patients. Sanger sequencing of genomic DNA from primary PTC tumors was performed for mutation detection and genotype-clinicopathological correlation of the tumor was analyzed. BRAF V600E and TERT promoter mutations were found in 63.7% (416 of 653) and 4.1% (27 of 653) of patients, respectively; the latter became 9.8% when only tumors ≥ 1.5 cm were analyzed. TERT promoter mutations occurred more frequently in BRAF mutation-positive cases compared to wild-type cases, being 5.3% in the former versus 2.1% in the latter (P = 0.050). BRAF and TERT promoter mutations were each significantly associated with high-risk clinicopathological features of PTC, such as old patient age, large tumor size, extrathyroidal invasion, capsular invasion, and advanced disease stages. Coexistence of BRAF V600E and TERT promoter mutations was particularly associated with high-risk clinicopathological features, as exemplified by extrathyroidal invasion seen in 54.5% (12/22) of patients harboring both mutations versus 9.9% (23/232) of patients harboring neither mutation (P < 0.001). Thus, this study, the largest on TERT mutation so far, demonstrates a significant role of BRAF V600E and TERT promoter mutations in the aggressiveness of PTC, which is particularly robust and cooperative when the two mutations coexist. These results, together with previous studies, establish a significant role of these mutations in the aggressiveness of PTC.

Potential relationship between Hashimoto's thyroiditis and BRAF(V600E) mutation status in papillary thyroid cancer.

BACKGROUND: The purpose of this study was to evaluate the potential relationship between Hashimoto's thyroiditis and BRAF(V600E) mutation status in patients with papillary thyroid carcinoma (PTC). METHODS: A total of 619 patients with PTC who underwent total thyroidectomy with lymph node dissection were enrolled in this study. Univariable and multivariate analyses were used. RESULTS: Hashimoto's thyroiditis was present in 35.9% (222 of 619) of PTCs. Multivariate logistic regressions showed that BRAF(V600E) mutation, sex, extrathyroidal extension, and lymph node metastasis were independent factors for Hashimoto's thyroiditis. Female sex, more frequent extrathyroidal extension, and a higher incidence of lymph node metastasis were significantly associated with PTCs accompanied by BRAF(V600E) mutation without Hashimoto's thyroiditis compared with PTCs accompanied by BRAF(V600E) mutation with Hashimoto's thyroiditis. CONCLUSION: Hashimoto's thyroiditis was negatively associated with BRAF(V600E) mutation, extrathyroidal extension, and lymph node metastasis. In addition, Hashimoto's thyroiditis was related to less lymph node metastasis and extrathyroidal extension in PTCs with BRAF(V600E) mutation. Therefore, Hashimoto's thyroiditis is a potentially protective factor in PTC. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1019-E1025, 2016.

Risk factors target in patients with post-thyroidectomy bleeding.

As the highly blood flow of thyroid gland post-thyroidectomy bleeding (PTB) is a serious and life-threatening complication. Our aim was to investigate factors that influenced bleeding after thyroidectomy. Between February 2008 and September 2012, the data of 4449 consecutive patients with thyroid diseases undergoing thyroidectomy were collected and analysed from the department of surgical oncology retrospectively. During the study period, 88 (2.0%) patients were identified to have clinically PTB. 6 risk factors were significantly related to PTB: gender (OR 3.243; 95% CI 2.078-5.061; P < 0.001), age (OR 1.025; 95% CI 1.006-1.043; P = 0.009), tumor size (OR 4.495; 95% CI 2.462-8.208; P < 0.001), postoperative hypertension (OR 2.195; 95% CI 1.006-1.043; P = 0.035), lymph node dissection (OR 3.384; 95% CI 2.146-5.339; P < 0.001) and Graves' disease (OR 3.744; 95% CI 1.920-7.303; P < 0.001). We addressed the most common explicit source of bleeding by reexploration: infrahyoid muscles (30/88), beside the laryngeal recurrent nerve (22/88), subcutaneous tissue (10/88) and superior pole (10/88). In our study, male gender, older age, tumor size > 3 cm, postoperative hypertension (SP > 150 mmHg), lymph node dissection and Graves' disease were independent risk factors for PTB. The sources of bleeding were identified more frequently in the infrahyoid muscles and beside the laryngeal recurrent nerve. It is helpful for surgeons to decide the potential bleeding points during the reexploration of PTB.

Prediction of central compartment lymph node metastasis in papillary thyroid microcarcinoma.

OBJECTIVES: We aimed to determine the predictive factors for central compartment lymph node metastasis (LNM) in papillary thyroid microcarcinoma (PTMC). DESIGN AND PATIENTS: We undertook a retrospective study of 291 patients treated for PTMC. The following criteria were assessed to predict the presence of central compartment LNM: sex, age, tumour multifocality, tumour size, tumour bilaterality, extracapsular spread (ECS), lateral neck LNM, coexistence of chronic lymphocytic thyroiditis, BRAF(V) (600E) mutation and ultrasonography (US) features. Univariate and multivariate analyses were performed to identify clinicopathological characteristics and US findings in predicting central compartment LNM from PTMC. RESULTS: The central compartment LNM affected 133 (45.7%) of 291 patients. With use of univariate and multivariate analyses, male gender (OR 2.020; P = 0.039), tumour size (>5 mm) (OR 3.687; P = 0.015), ESC (OR 2.330; P = 0.044), lateral LNM (OR 15.075; P = 0.000) and BRAF(V) (600E) mutation (OR 2.464; P = 0.000) were independently correlated with central compartment LNM. Age, tumour multifocality, tumour bilaterality, coexistence of chronic lymphocytic thyroiditis and US characteristics were not significantly related to the presence of central compartment LNM. We have also developed a nomogram to predict the probability of central compartment LNM for an individual patient. The sensitivity was 71.9% and specificity was 70.3%, with an under the receiver operating characteristic (ROC) curve of 0.772. CONCLUSIONS: A prophylactic neck dissection of the central compartment should be considered particularly in PTMC patients with male gender, a >5 mm tumour size, ECS of the tumours, lateral LNM and positive BRAF(V) (600E) mutation.

Primary thyroid T-lymphoblastic lymphoma: a case report and review of the literature.

Most thyroid lymphomas are B-lineage, and T-cell lymphomas are rare. Here, we report a case of primary T-cell lymphoblastic lymphoma (T-LBL) of the thyroid gland. A 15-year-old boy presented with a painless thyroid mass. Ultrasonographic examination revealed a hypoechoic thyroid nodule measuring 4.6 cm × 1.9 cm × 3.4 cm. The thyroid function and antibodies were normal. Hemithyroidectomy was performed. Intraoperative frozen section was suggestive of malignant lymphoma. Histological examination showed diffuse round to oval medium sized cells with high nuclear/cytoplasmic ratio, finely dispersed chromatin, scanty cytoplasm, and numerous mitoses. Immunohistochemical studies revealed malignant cells were positive for terminal deoxynucleotidyltransferase, CD5, CD7, CD8, CD10, CD45RO, CD99, CD79a, CD3, CD1a and Ki-67 (>40%) and negative for CD34, CD20, BCL6, CD23, BCL2, Pax5 and EBV. A diagnosis of thyroid T-LBL was made. The patient was treated by intensive chemotherapy followed by allogeneic hematopoietic stem cell transplantation and has been in event-free survival for 65 months. The patient was unique because no cases of thyroid T-LBL have been previously reported, to our knowledge. Moreover, intensive chemotherapy followed by alloHSCT might be one of the adoptive options in therapy for this aggressive disease.

Effect and mechanism of the metastasis suppressor gene BRMS1 on the migration of breast cancer cells.

OBJECTIVE: To study the effect of the transfected Breast cancer metastasis suppressor 1 (BRMS1) gene on the migration of breast cancer cells and the possible mechanisms involved. METHODS: MDA-MB-231HM cells which have a high propensity of metastasize to lung was sieved from MDA-MB-231 and its derivative cells stable transfected with BRMS1 were used to study in vitro. Cell migratory ability was observed. The cellular cyclic adenylic acid (cAMP) concentration was tested by radioimmunoassay (RIA). The activity of adenylate cyclase (AC), phosphodiesterase (PDE) and protein kinase A (PKA) were measured by enzyme immunoassay (EIA) and (γ-(32)P) ATP incorporation. The effect of BRMS1 on connexins (Cx) expression was analyzed by by RT-PCR and Western blot. RESULTS: Overexpression of BRMS1 significantly inhibited cell migration in MDA-MB-231HM cells in vitro. However, BRMS1's effect on cell migration could be eliminated after pretreating with pertussis toxin (PTX). BRMS1 overexpression increased cellular cAMP and PKA activity by activating the activity of AC. Furthermore, BRMS1 overexpression up-regulated Cx26 expression, whereas Cx32, Cx43 expressions did not changed. CONCLUSION: The present study indicated G-protein-coupled cAMP signaling pathway was involved in BRMS1 related MDA-MB-231HM cells migration, and BRMS1 could change connexins (Cx) expression profiles through increasing expression of Cx26 in cells.