Huijuan Feng

Global microRNA profiles and signaling pathways in the development of cardiac hypertrophy

Hypertrophy is a major predictor of progressive heart disease and has an adverse prognosis. MicroRNAs (miRNAs) that accumulate during the course of cardiac hypertrophy may participate in the process. However, the nature of any interaction between a hypertrophy-specific signaling pathway and aberrant expression of miRNAs remains unclear. In this study, Spague Dawley male rats were treated with transverse aortic constriction (TAC) surgery to mimic pathological hypertrophy. Hearts were isolated from TAC and sham operated rats (n=5 for each group at 5, 10, 15, and 20 days after surgery) for miRNA microarray assay. The miRNAs dysexpressed during hypertrophy were further analyzed using a combination of bioinformatics algorithms in order to predict possible targets. Increased expression of the target genes identified in diverse signaling pathways was also analyzed. Two sets of miRNAs were identified, showing different expression patterns during hypertrophy. Bioinformatics analysis suggested the miRNAs may regulate multiple hypertrophy-specific signaling pathways by targeting the member genes and the interaction of miRNA and mRNA might form a network that leads to cardiac hypertrophy. In addition, the multifold changes in several miRNAs suggested that upregulation of rno-miR-331*, rno-miR-3596b, rno-miR-3557-5p and downregulation of rno-miR-10a, miR-221, miR-190, miR-451 could be seen as biomarkers of prognosis in clinical therapy of heart failure. This study described, for the first time, a potential mechanism of cardiac hypertrophy involving multiple signaling pathways that control up- and downregulation of miRNAs. It represents a first step in the systematic discovery of miRNA function in cardiovascular hypertrophy.

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.

Lymph node characteristics for predicting locoregional recurrence of papillary thyroid cancer in adolescents and young adults

PURPOSE To determine lymph node (LN) characteristics predictive of locoregional recurrence (LRR) in adolescent and young adult (AYA) ages 15-39years presenting with papillary thyroid cancer (PTC) and cervical pathologically proven LN metastases (pN1). METHODS AND MATERIALS Retrospective chart review was performed for all patients with PTC and nodal metastases who had undergone total thyroidectomy, LN dissection, and postoperative radioactive iodine therapy in a university hospital between 2006 and 2014. Clinical and histopathologic markers that were independently associated with tumor recurrence were evaluated. RESULTS In all, 329 consecutive AYA patients were included. At a median follow-up of 57months, twenty patients (6.08%) experienced LRR. No patients had distant metastases, and no patients died during follow-up. Based on Cox regression analysis, the presence of extranodal extension and more than six metastatic LNs at presentation were independent predictive factors for LRR. However, age, male sex, total number of LNs resected, pN1b, LN ratio, size of the largest metastatic LN, extrathyroidal extension, tumor size, bilateral tumor, multifocality, vascular invasion, and Hashimoto thyroiditis were not correlated with an increased risk for LRR. A cutoff of more than six positive nodes optimally predicted future LRR with sensitivity and specificity values of 85.0% and 60.2%, respectively. CONCLUSION The presence of extranodal extension and more than six metastatic LNs were independent predictors of LRR in AYA patients with pN1 disease. Evaluation of these prognostic factors appears to help identify patients who require close monitoring.

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.