MicroRNA-375-3p inhibitor suppresses angiotensin II-induced cardiomyocyte hypertrophy by promoting lactate dehydrogenase B expression.

Cardiac hypertrophy is a myocardial enlargement due to overload pressure, and the primary cause of heart failure. We investigated the function of miR-375-3p in cardiac hypertrophy and its regulating mechanisms. miR-375-3p was upregulated in hearts of the transverse aortic constriction rat model and angiotensin II (Ang II)-induced primary cardiomyocyte hypertrophy model; the opposite was observed for lactate dehydrogenase B (LDHB) protein expression. miR-375-3p knockdown reduced the surface area of primary cardiomyocytes increased by Ang II treatment and decreased the B-natriuretic peptide (BNP) and ß-myosin heavy chain (ß-MHC) messenger RNA (mRNA) and protein levels. miR-375-3p was also observed to directly target LDHB. LDHB knockdown increased the surface area of Ang II-treated primary cardiomyocytes and increased the BNP and ß-MHC mRNA and protein levels. LDHB knockdown attenuated the effects of miR-375-3p on the surface area of primary cardiomyocytes and BNP and ß-MHC levels. Therefore, miR-375-3p inhibitor suppresses Ang II-induced cardiomyocyte hypertrophy by promoting LDHB expression.

SIZE OF THE LARGEST METASTATIC FOCUS TO THE LYMPH NODE IS ASSOCIATED WITH INCOMPLETE RESPONSE OF PN1 PAPILLARY THYROID CARCINOMA.

Objective: To evaluate the influence of the size of the metastatic focus in lymph nodes (LNs) on therapeutic response among papillary thyroid cancer (PTC) and cervical pathologically proven LN metastases (pN1). Methods: Patients with pN1 PTC who underwent total or near-total thyroidectomy, LN dissection, and postoperative radioactive iodine therapy in a university hospital between 2014 and 2016 were retrospectively reviewed. Furthermore, 554 patients were assigned to three groups according to the size of the metastatic focus in the LNs (≤0.2 cm, 0.2 to 1.0 cm, ≥1.0 cm). Structural incomplete response (SIR) was defined as structural or functional evidence of disease with any thyroglobulin level and/or anti-thyroglobulin antibodies. Results: Among the 554 patients, the proportion of patients with SIR was 2.5% (4/161) in group 1, 13.9% (37/267) in group 2, and 46.8% (59/126) in group 3 (χ2 = 100.073; P<.001). The optimal cutoff value of the size of the largest metastatic focus to the LNs was 0.536 cm to predict SIR with a corresponding sensitivity of 0.82, a specificity of 0.716, and an area under the curve of 0.821 (95% confidence interval [CI], 0.777 to 0.864; P<.001). Size of the largest metastatic focus to the LNs was confirmed to be an independent predictive factor for SIR (odds ratio, 9.650; 95% CI, 4.925 to 18.909; P<.001). Conclusion: In patients with pN1 PTC, there is an association between the size of the largest metastatic focus to the LNs and incomplete response. Abbreviations: AJCC = American Joint Committee on Cancer; ATA = American Thyroid Association; BIR = biochemical incomplete response; CI = confidence interval; ER = excellent response; ETE = extranodal extension; 18F-FDG = 18F-fluorodeoxyglucose; IDR = indeterminate response; LN = lymph node; OR = odds ratio; PET/CT = positron emission tomography/computed tomography; pN1 = pathologically proven LN metastases; PTC = papillary thyroid carcinoma; RAI = radioactive iodine; ROC = receiver operating characteristic; SIR = structural incomplete response; sTg = stimulated thyroglobulin; TgAb = anti-thyroglobulin antibody; TSH = thyroid-stimulating hormone.

Radiation dose rates of differentiated thyroid cancer patients after 131I therapy.

Postoperative 131I treatment for differentiated thyroid cancer (DTC) can create a radiation hazard for nearby persons. The present prospective study aimed to investigate radiation dose rates in 131I-treated DTC patients to provide references for radiation protection. A total of 141 131I-treated DTC patients were enrolled, and grouped into a singular treatment (ST) group and a repeated treatment (RT) group. The radiation dose rate of 131I-treated patients was measured. The rate of achieving discharge compliance and restricted contact time were analyzed based on Chinese regulations. Multivariate logistic regression analysis was used to analyze the independent factors associated with the clearance of radioiodine. The rate of achieving discharge compliance (131I retention < 400 MBq) was 79.8 and 93.7% at day 2 (D2) for the ST and RT groups, respectively, and reached 100% at D7 and D4, respectively. The restricted contact time with 131I-treated patients at 0.5 m for medical staff, caregivers, family members, and the general public ranged from 4 to 7 days. Multivariate logistic regression analysis showed that the 24-h iodine uptake rate was the only significant factor associated with radioiodine clearance. For the radiation safety of 131I-treated DTC patients, the present results can provide radiometric data for radiation protection.

RISK FACTORS FOR NONREMISSION AND PROGRESSION-FREE SURVIVAL AFTER I-131 THERAPY IN PATIENTS WITH LUNG METASTASIS FROM DIFFERENTIATED THYROID CANCER: A SINGLE-INSTITUTE, RETROSPECTIVE ANALYSIS IN SOUTHERN CHINA.

OBJECTIVE: Prognostic factors related to progression-free survival (PFS) have not received much attention in the literature regarding iodine-131 ((131)I) therapy for patients with differentiated thyroid cancer and lung metastases. We sought to explore the factors associated with PFS and nonremission in a group of patients with differentiated thyroid cancer and pulmonary metastases at initial diagnosis and to investigate the impact of (131)I therapy on pulmonary function and peripheral blood counts in the same cohort of patients. METHODS: The medical records of 1,050 patients with differentiated thyroid cancer treated at the Zhujiang Hospital of Southern Medical University from January 2006 to January 2015 were retrospectively reviewed. Among them, 107 patients fulfilled the inclusion criteria. RESULTS: Multivariate Cox regression analysis indicated that age ≥45 years and (131)I nonavidity were independent risk factors for disease progression. Multivariate logistic regression analysis revealed that pulmonary nodule size ≥1 cm and (131)I nonavidity were the strongest risk factors predicting nonremission. Varying cumulative (131)I dosage had no association with posttreatment pulmonary function or peripheral blood cell counts. CONCLUSION: Similar to earlier studies, our results confirm that (131)I nonavidity was associated with an increased risk of disease progression and greater odds of nonremission. In addition, patients with differentiated thyroid cancer and lung metastases with pulmonary nodules ≥1 cm had a reduced likelihood of achieving remission. Furthermore, special attention is needed when monitoring patients over 45 years at a higher risk of disease progression. ABBREVIATIONS: CI = confidence interval DTC = differentiated thyroid cancer (18)F-FDG = fluoro-18 fluorodeoxyglucose FEF = forced expiratory flow FTC = follicular thyroid cancer FVC = forced vital capacity GR = granulocytes Hb = hemoglobin HR = hazard ratio (131)I = iodine-131 LN = lymph node OR = odds ratio OS = overall survival PET/CT = positive positron emission tomography/computed tomography PFS = progression-free survival PT = partial thyroidectomy PTC = papillary thyroid cancer RAI = radioactive iodine RBC = red blood cell Tg = thyroglobulin TgAb = thyroglobulin antibody TSH = thyroid-stimulating hormone TT = total thyroidectomy WBC = white blood cells WBS = whole body scan.

Postoperative thyroid remnants for differentiated thyroid cancer may not affect the outcome of high-dose radioiodine therapy.

OBJECTIVES: This study aims to provide a way to estimate the volume of the thyroid remnant and determine its relationship with the outcome of radioiodine (RAI) therapy in depth. MATERIALS AND METHODS: A retrospective analysis was performed on patients who underwent initial RAI therapy between January 2010 and January 2016. The patients were divided into five groups based on the thyroid remnant estimated by post-therapy whole-body scan(post-Rx WBS), thyroid scintigraphy and ultrasonography. The relationship between the volume of thyroid remnant and the outcome of RAI therapy were evaluated by univariate analysis and multivariate analysis. RESULTS: Of 703 patients, the majority could be found different size of thyroid remnants using the three imaging methods, and only few patients(2.1%) could reach no thyroid remnant. There was no association between the volume of thyroid remnant and the outcome of RAI therapy in univariate analysis (χ2 = 1.633, P = 0.652) and multivariate analysis (P > 0.05). In the subgroup of patients with high-risk factors, there was still no significant difference (intermediate risk subgroup: P = 0.338 vs high risk subgroup: P = 0.263). CONCLUSION: Different sizes of thyroid remnants were left after surgery. However, in high radioiodine activity, the volume of thyroid remnants may not affect the outcome of RAI therapy even in patients with some high-risk factors, so the high radioiodine activities may resolve the the problem caused by thyroid remnants in some cases.

Systematic evaluation of salivary gland damage following I-131 therapy in differentiated thyroid cancer patients by quantitative scintigraphy and clinical follow-up.

OBJECTIVES: Radioiodine therapy is a common adjunct to thyroidectomy in papillary thyroid cancer treatment. However, a variety of associated adverse effects have been reported. In this study, we assessed radioiodine-induced salivary gland dysfunction using quantitative scintigraphy, and evaluated the associated complications. METHODS: Patients were divided into five groups on the basis of the cumulative I-131 dosage received. Scintigraphic dynamic images of the salivary glands were obtained and converted into clinically relevant parameters: uptake index (UI), maximum secretion rate (%SR), and combined gland function scores. Patients were followed up for 3-66 months and interviewed for side effects including xerostomia, taste alteration, bitter taste, dental caries, xerophthalmia, and pain/swelling. RESULTS: An increase in I-131 doses resulted in a reduction in the UI and %SR and an increase in the combined scintigraphy score. Parotid glands were more affected than submandibular glands. A cumulative dosage of greater than 600 mCi resulted in complete loss of %SR in the parotid glands. No significant difference in either the UI or the %SR was observed between nontreated patients and patients receiving an I-131 dosage of up to 150 mCi. The occurrence of xerostomia was significantly correlated with the gland scintigraphic score, the number of treatment cycles, and I-131 dosage. The occurrence of pain and swelling was extremely low and only lasted for a short time. CONCLUSION: Although the side effects associated with radioiodine treatment were apparent, they were usually small and temporary. Nevertheless, more consideration should be placed on careful dosing of I-131.