Associations between immune cell traits and autoimmune thyroid diseases: a bidirectional two-sample mendelian randomization study.

Autoimmune thyroid diseases (AITDs), mainly including Graves' disease (GD) and Hashimoto's thyroiditis (HT), are common autoimmune disorders characterized by abnormal immune responses targeting the thyroid gland. We conducted a bidirectional two-sample MR analysis using the largest dataset of peripheral immune cell phenotypes from Sardinia, and the AITD dataset from the 10th round of the FinnGen and the UK Biobank project. Instrumental variables (IVs) were rigorously selected based on the three assumptions of MR and analyzed using the Wald ratio, inverse-variance weighted (IVW), MR-Egger, and weighted median methods. Additionally, sensitivity analyses were performed using Cochrane's Q, the Egger intercept, the MR-PRESSO, and the leave-one-out (LOO) method to ensure the robustness of the results. The Steiger test was utilized to identify and exclude potential reverse causation. The results showed that 3, 3, and 11 immune cell phenotypes were significantly associated with the risk of AITD. In GD, the proportion of naive CD4-CD8- (DN) T cells in T cells and the proportion of terminally differentiated CD4+T cells in T cells showed the strongest inducing and protective effects, respectively. In HT, lymphocyte count and CD45 on CD4+T cells showed the strongest inducing and protective effects, respectively. In autoimmune hypothyroidism, CD127 CD8+T cell count and terminally differentiated DN T cell count exhibited the strongest inducing and protective effects, respectively. Through MR analysis, our study provides direct genetic evidence of the impact of immune cell traits on AITD risk and lays the groundwork for potential therapeutic and diagnostic target discovery.

Ultrasound radiomics based on axillary lymph nodes images for predicting lymph node metastasis in breast cancer.

Objectives: To determine whether ultrasound radiomics can be used to distinguish axillary lymph nodes (ALN) metastases in breast cancer based on ALN imaging. Methods: A total of 147 breast cancer patients with 41 non-metastatic lymph nodes and 109 metastatic lymph nodes were divided into a training set (105 ALN) and a validation set (45 ALN). Radiomics features were extracted from ultrasound images and a radiomics signature (RS) was built. The Intraclass correlation coefficients (ICCs), Spearman correlation analysis, and least absolute shrinkage and selection operator (LASSO) methods were used to select the ALN status-related features. All images were assessed by two radiologists with at least 10 years of experience in ALN ultrasound examination. The performance levels of the model and radiologists in the training and validation subgroups were then evaluated and compared. Result: Radiomics signature accurately predicted the ALN status, achieved an area under the receiver operator characteristic curve of 0.929 (95%CI, 0.881-0.978) and area under curve(AUC) of 0.919 (95%CI, 95%CI, 0.841-0.997) in training and validation cohorts respectively. The radiomics model performed better than two experts' prediction of ALN status in both cohorts (P<0.05). Besides, prediction in subgroups based on baseline clinicopathological information also achieved good discrimination performance, with an AUC of 0.937, 0.918, 0.885, 0.930, and 0.913 in HR+/HER2-, HER2+, triple-negative, tumor sized ≤ 3cm and tumor sized>3 cm, respectively. Conclusion: The radiomics model demonstrated a good ability to predict ALN status in patients with breast cancer, which might provide essential information for decision-making.

RETRACTED: Zhou et al. Pyrvinium Treatment Confers Hepatic Metabolic Benefits via ß-Catenin Downregulation and AMPK Activation. Pharmaceutics 2021, 13, 330.

The authors and the journal retract the article, 'Pyrvinium Treatment Confers Hepatic Metabolic Benefits via ß-Catenin Downregulation and AMPK Activation' [...].

Primary synovial sarcoma of the thyroid gland: a CARE compliant case report and literature review.

Rationale: Synovial sarcoma is a subtype of soft tissue sarcoma. Synovial sarcoma in the head and neck region is relatively unusual. Primary synovial sarcoma of the thyroid gland (PSST) is first reported in 2003 by Inako Kikuchi. PSST is extremely rare with only 15 cases documented globally. PSST shows rapid disease progression and a relatively poor prognosis. However, diagnosis and therapy are challenging for clinical surgeons. In this article, we reported the 16th PSST case and reviewed the PSST cases globally for further clinical application. Patient concerns: The patient was referred to us because of gradually worsened dyspnea and dysphagia for 20 days. Physical examination showed a 5 × 4 cm mass with a clear boundary and good mobility. Contrast-enhanced ultrasonography (CEUS) and computed tomography (CT) showed a mass in the isthmus of the thyroid gland. The imageology diagnosis tends to be a benign thyroid nodule. Diagnosis: After surgery, histopathology, immunohistochemistry, and fluorescence, in situ hybridization indicated the mass to be primary synovial sarcoma of the thyroid gland with no local and distant metastasis. Interventions: The patient underwent total thyroidectomy and dissected the lymph nodes in the central compartment. This patient received postoperative chemotherapy (a combination of ifosfamide and epirubicin for five cycles). Patients tolerated chemotherapy well. No recurrence was found during the 9-month follow-up. Lessons: Although PSST is an extremely rare disease, we should raise our awareness when we encounter a rapidly growing, cystic-solid mixed thyroid mass with neck compression symptoms to avoid misdiagnosis. Intraoperatively, surgeons should refine surgical procedures to avoid capsular rupture and tumor local implantation metastasis. Intraoperative frozen section pathology is necessary sometimes, especially when the diagnosis could not be established before surgery.

Newly found variations of the right posterior portal vein identified radiologically in 1,003 Chinese patients: a cross-sectional study.

Background: The anatomy of the right posterior portal vein (RPPV) plays an important role in planning hepatic resection, living transplantation and interventional radiological procedures, yet the incidence of variations of RPPV without a common trunk in Chinese persons is still unclear. Therefore, we conducted this study and discussed its clinical implications. Methods: A retrospective analysis of multidetector computed tomography (MDCT) scans was performed in 1,933 patients with various abdominal pathologies between September 28, 2018 through May 23, 2019. After excluding 930 patients, a total of 1,003 patients were included in this study. Variations of the RPPV without a common trunk were classified according to classification standards. Results: A total of 1,003 patients were included. RPPV without a common trunk was found in 216 (21.54%, 216/1,003) patients. Among them, we identified three variations of the origin from the right portal vein (RPV): first separate origin of P6, P7, or simultaneous separate origin of P6 and P7, and the incidences of these three variations were 1.50% (15/1,003), 6.58% (66/1,003) and 13.46% (135/1,003), respectively. Among 1,003 patients included in this study, 787 patients (78.46%, 787/1,003) showed that RPPV normally divided into P6 and P7 branches. Conclusions: Variations of the RPPV without a common trunk were not rare in Chinese population. Knowledge of this anatomic variation of the RPPV is extremely important for hepatic and transplant surgeons and interventional radiologists.

Association of long-term visit-to-visit variability of HbA1c and fasting glycemia with hypoglycemia in type 2 diabetes mellitus.

Background: Self-management of blood glucose levels to avoid hypoglycemia is vital for patients with type 2 diabetes mellitus (T2DM). The association between specific metrics of glycemic variability (glycosylated hemoglobin A1c [HbA1c] and fasting plasma glucose [FPG]) and severe hypoglycemia has not been fully studied in patients with T2DM. Methods: In this post hoc analysis, patients with established T2DM with a high risk of cardiovascular disease were included in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study. The Cox proportional hazards model was used to investigate the relationship between glycemic variability and hypoglycemia requiring medical assistance (HMA) and hypoglycemia requiring any third-party assistance (HAA). The prognostic value of HbA1c/FPG variability for our predefined outcomes was compared using Harrell's C method. Results: After adjusting for confounders, each increase in HbA1c variability of 1 standard deviation (SD) indicated a higher risk of HAA (hazard ratio [HR]: 1.10; 95% confidence interval [CI]: 1.03-1.16; P < 0.01) and HMA events (HR: 1.11; 95% CI: 1.03-1.20; P < 0.01). Meanwhile, each increase in FPG variability of 1 SD increased the risk of HAA (HR: 1.40; 95% CI: 1.31-1.49; P < 0.01) and HMA events (HR: 1.46; 95% CI: 1.35-1.57; P < 0.01). Meanwhile, models, including FPG variability, had better prognostic value for our predefined outcomes than HbA1c variability (P < 0.01). Conclusions: Increased visit-to-visit variability in HbA1c and fasting glycemia is associated with a greater risk of severe hypoglycemic events in T2DM patients. FPG variability is a more sensitive indicator than HbA1c variability. Trial registration: http://www.clinicaltrials.gov. Unique identifier: NCT00000620.

The Role of Thyroglobulin in Preoperative and Postoperative Evaluation of Patients With Differentiated Thyroid Cancer.

Thyroglobulin (Tg) is secreted by thyroid follicular cells and stored in the thyroid follicular lumen as a component of thyroid hormone. It is known that both benign and well-differentiated malignant thyroid tissue can secrete Tg. In recent years, growing lines of evidence have shown that Tg plays an important role in the diagnosis and metastasis of preoperative differentiated thyroid carcinoma (DTC). The levels of Tg, whether in the serum or in a fine-needle aspiration washout fluid, are usually viewed as an excellent indicator in the monitoring of postoperative DTC, including the guidance and evaluation of radioactive iodine ablation. Nevertheless, some factors limit the application of Tg, such as the method used to measure Tg and the presence of Tg antibodies. This review aimed to summarize the role of Tg in the preoperative and postoperative evaluation of patients with DTC, and the factors influencing Tg. This review could provide a reference for a more accurate application of Tg in patients with DTC.

A Risk Model Developed Based on Necroptosis Predicts Overall Survival for Hepatocellular Carcinoma and Identification of Possible Therapeutic Drugs.

Background: Necroptosis is a form of regulatory cell death (RCD) that attracts and activates immune cells, resulting in pro-tumor or anti-tumor effects. The purpose of this study was to investigate genes associated with necroptosis, to construct a risk score for predicting overall survival in patients with hepatocellular carcinoma, and to find potentially effective drugs. Methods: The three algorithms ssGSEA, EPIC, and ESTIMATE were used to quantify the immune cell infiltration of the samples, differentially expressed genes (DEGs) analysis, and weighted gene co-expression network analysis were used to screen necroptosis related genes. Variables were screened according to random survival forest analysis, and combinations with significant p-values and a low number of genes were defined as prognostic signatures by using log-rank test after gene combination. Based on the sensitivity data of PRISM and CTRP2.0 datasets, we predicted the potential therapeutic agents for high-NRS patients. Results: Seven genes such as TOP2A were used to define necroptosis-related risk score (NRS). The prognostic value of risk score was further validated, where high NRS was identified as a poor prognostic factor and tended to have higher grades of histologic grade, pathologic stage, T stage, BCLC, CLIP, and higher AFP. Higher NRS was also negatively correlated with the abundance of DCs, Neutrophils, Th17 cells, Macrophages, Endothelial, and positively correlated with Th2 cells. Necroptosis is often accompanied by the release of multiple cytokines, and we found that some cytokines were significantly correlated with both NRS and immune cells, suggesting that necroptosis may affect the infiltration of immune cells through cytokines. In addition, we found that TP53 mutations were more common in samples with high NRS, and these mutations may be associated with changes in NRS. Patients with high NRS may be more sensitive to gemcitabine, and gemcitabine may be an effective drug to improve the prognosis of patients with high NRS, which may play a role by inhibiting the expression of TOP2A. Conclusions: We constructed a necroptosis-related scoring model to predict OS in HCC patients, and NRS was associated with immune response, TP53 mutation, and poor clinical classification in HCC patients. In addition, gemcitabine may be an effective drug for high-NRS patients.

Hashimoto's Thyroiditis: A "Double-Edged Sword" in Thyroid Carcinoma.

Background: The prevalence of thyroid carcinoma (TC) and Hashimoto's thyroiditis (HT) has been increasing dramatically over the past decades. We investigated the relationship between HT and TC. Methods: We followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines for carrying out and reporting this meta-analysis. The literature from January 1, 2010 to December 31, 2020, regardless of region and publication type, was searched comprehensively in PubMed, Embase, Web of Science, and Cochrane Library databases. After careful selection and data extraction, the pooled odds ratio of various clinical characteristics in 39 studies were calculated. Publication bias was analyzed using funnel plots. Results: Meta-analysis of 39 original research articles showed HT to be a risk factor of TC (pooled odds ratio = 1.71; 95% confidence interval, 1.57-1.80; p < 0.00001) and papillary thyroid carcinoma (1.67, 1.51-1.85, <0.00001). Patients with papillary thyroid carcinoma (PTC) combined with HT were more likely to have multifocal carcinomas. The prevalence of an extrathyroidal extension, metastasis, BRAFV600E mutation, and recurrence was significantly lower in patients with PTC combined with HT. Conclusions: HT is a "double-edged sword" in TC patients. HT increases the risk of TC and PTC but is a protective factor against PTC progression.

Pyrvinium Treatment Confers Hepatic Metabolic Benefits via ß-Catenin Downregulation and AMPK Activation.

Genetic evidence has indicated that ß-catenin plays a vital role in glucose and lipid metabolism. Here, we investigated whether pyrvinium, an anthelmintic agent previously reported as a down-regulator of cellular ß-catenin levels, conferred any metabolic advantages in treatment of metabolic disorders. Glucose production and lipid accumulation were analyzed to assess metabolic response to pyrvinium in hepatocytes. The expression of key proteins and genes were assessed by immunoblotting and RT-PCR. The in vivo efficacy of pyrvinium against metabolic disorders was evaluated in the mice fed with a high fat diet (HFD). We found that pyrvinium inhibited glucose production and reduced lipogenesis by decreasing the expression of key genes in hepatocytes, which were partially elicited by the downregulation of ß-catenin through AXIN stabilization. Interestingly, the AMPK pathway also played a role in the action of pyrvinium, dependent on AXIN stabilization but independent of ß-catenin downregulation. In HFD-fed mice, pyrvinium treatment led to improvement in glucose tolerance, fatty liver disorder, and serum cholesterol levels along with a reduced body weight gain. Our results show that small molecule stabilization of AXIN using pyrvinium may lead to improved glucose and lipid metabolism, via ß-catenin downregulation and AMPK activation.

Total versus near-total thyroidectomy in Graves' disease: a systematic review and meta-analysis of comparative studies.

BACKGROUND: Total thyroidectomy (TT), near-total thyroidectomy (NT), and subtotal thyroidectomy (ST) are three surgical procedures for Graves' disease (GD) patients, but most previous studies have only evaluated the complications of TT versus ST or TT/NT versus ST; there is not a meta-analysis of NT versus TT, so whether NT is superior to TT for GD patients still unclear. METHODS: We comprehensively searched PubMed, Embase, Web of Science, and the Cochrane Library, without restriction to region, publication type, or language, on 10 June, 2020. We conducted this systematic review and meta-analysis of all included studies assessing the two surgical procedures. RESULTS: In total, 528 cases were identified from two randomized controlled trials (RCTs) and three retrospective studies. The incidence of permanent hypoparathyroidism after NT was lower than with TT [odds ratio (OR), 0.22; 95% confidence interval (CI), 0.06-0.80; P=0.02], and there was no statistical difference in the recurrence of hyperthyroidism (OR, 0.33; 95% CI, 0.01-8.12; P=0.50) and other postoperative complications (P>0.05). CONCLUSIONS: NT for GD was superior to TT regarding permanent hypoparathyroidism, but there was no significant difference in preventing recurrent hyperthyroidism, as well as the other postoperative complications.

Long noncoding RNA TPT1-AS1 promotes the progression and metastasis of colorectal cancer by upregulating the TPT1-mediated FAK and JAK-STAT3 signalling pathways.

Tumour protein translationally controlled 1 (TPT1) antisense RNA 1 (TPT1-AS1) is known to be involved in the development and metastasis of cervical and ovarian cancers; however, its biological role in colorectal cancer (CRC) remains unknown. This study aimed to determine the function and mechanism of action of TPT1-AS1 in the progression and metastasis of CRC. Elevated TPT1-AS1 levels were observed in CRC tissues. Furthermore, the high expression levels were found to be correlated with unfavourable clinicopathological characteristics in CRC. Cell function experiments demonstrated that TPT1-AS1 depletion impeded cell proliferation, migration and invasion and enhanced cell adhesion; it also attenuated tumorigenesis and metastasis in vivo. Additionally, TPT1-AS1 was predominately located in the nuclei of the cells and could upregulate the expression of TPT1 by recruiting mixed lineage leukaemia protein-1 (MLL1), which increased the trimethylation of H3K4 me3 in the TPT1 promoter region and subsequently activated FAK and JAK-STAT3 signalling cascades. The inhibition of FAK activation by PF573228 significantly attenuated the oncogenic effect of TPT1-AS1. These findings indicated that TPT1-AS1 promoted tumour progression and metastasis in CRC by upregulating TPT1 levels and activating the FAK and JAK-STAT3 signalling pathways. Thus, TPT1-AS1 may be considered as a potential therapeutic target for CRC.

Long non-coding RNA DIO3OS/let-7d/NF-κB2 axis regulates cells proliferation and metastasis of thyroid cancer cells.

Due to the steadily rising morbidity and mortality, thyroid cancer remains the most commonly seen endocrine cancer. The present study attempted to investigate the mechanism from the perspective of long non-coding RNA (lncRNA) regulation. We identified 53 markedly increased lncRNAs in thyroid cancer samples according to TCGA data. Among them, high lncRNA DIO3OS expression was a risk factor for thyroid cancer patients' poorer overall survival. DIO3OS showed to be considerably increased within thyroid cancer tissue samples and cells. Knocking down DIO3OS within thyroid carcinoma cells suppressed cancer cell viability, the capacity of DNA synthesis, cell invasion, as well as cell migration; besides, proliferating markers, ki-67 and PCNA, were decreased by DIO3OS knockdown. Cancer bioinformatics analysis suggested that NF-κB2 might be related to DIO3OS function in thyroid cancer carcinogenesis. NF-κB2 was positively correlated with DIO3OS, and DIO3OS knockdown decreased NF-κB2 protein levels. Knocking down NF-κB2 within thyroid carcinoma cells suppressed cancer cell viability, the capacity of DNA synthesis, cell invasion, cell migration, and the protein levels of proliferating markers. Let-7d directly targeted DIO3OS and NF-κB2; DIO3OS knockdown upregulated let-7d expression. The overexpression of let-7d suppressed cancer cell viability, the capacity of DNA synthesis, cell invasion, cell migration, as well as the protein levels of proliferating markers. Let-7d inhibition remarkably attenuated the functions of DIO3OS knockdown in NF-κB2 expression and thyroid cancer cell phenotype. In conclusion, DIO3OS/let-7d/NF-κB2 axis regulates the viability, DNA synthesis capacity, invasion, and migration of thyroid cancer cells. The clinical application of this axis needs further in vivo and clinical investigation.

The Predictive Role of PIK3CA Mutation Status on PI3K Inhibitors in HR+ Breast Cancer Therapy: A Systematic Review and Meta-Analysis.

AIM: To evaluate the impact of PIK3CA mutation status on clinical outcomes of HR+ breast cancer treated with PI3K inhibitors. METHODS: A comprehensive literature search was conducted in online databases from inception to December 31, 2019. The main characteristics and prognostic data of each eligible study were extracted. The odds ratio (OR) for the overall response rate (ORR) and hazard ratio (HR) for progression-free survival (PFS) were estimated using the fixed-effects Mantel-Haenszel model. RESULTS: A total of 8 studies involving 2670 patients were included for analysis. Overall, the clinical outcomes of PI3K inhibitors were significantly influenced by PIK3CA mutation status in HR+ breast cancer. After the treatment of PI3K inhibitors, HR+ breast cancer patients with PIK3CA mutations presented better ORR (PIK3CA-mutated group: OR = 1.98 [95% CI, 1.46 to 2.70]; PIK3CA wild-type group: OR = 1.09 [95% CI, 0.78 to 1.53]) and better PFS (PIK3CA-mutated group: HR = 0.65 [95% CI, 0.55 to 0.76]; PIK3CA wild-type group: HR = 0.87 [95% CI, 0.70 to 1.09]). No publication bias was detected for ORR and PFS in our analysis. CONCLUSION: In this meta-analysis, it suggests that the association between clinical outcomes of PI3K inhibitors and PIK3CA mutation status is dramatic. PIK3CA mutations were a favorable factor in the clinical outcomes of HR+ breast cancer treated with PI3K inhibitors.

GLUT1/3/4 as novel biomarkers for the prognosis of human breast cancer.

BACKGROUND: Anomalous expression of glucose transporters (GLUTs) has been observed in a variety of tumor tissues. Although GLUT factors have been shown to have prognostic value for some cancer types, detailed bioinformatics investigation of the factors contributing to the prognostic prediction for patients with breast cancer (BC) has not yet been performed. METHODS: In this study, we examined the transcription levels of GLUT1, GLUT3, and GLUT4 and their associations with prognostic clinical data in patients with BC from the ONCOMINE database, using gene expression profiling interactive analysis (GEPIA), Kaplan-Meier (KM) plotter, and cBioPortal online tools. RESULTS: The transcription level of GLUT1 was significantly higher in the BC samples than in the normal tissues, whereas the levels of GLUT3 and GLUT4 were lower in the BC samples. The expression levels of GLUT1 and GLUT3 were associated with the cancer clinical stage. Consistently, survival analysis demonstrated that a high expression level of GLUT1 was associated with low relapse-free survival (RFS) in patients with BC, whereas high GLUT3 and GLUT4 levels predicted a longer RFS in these patients. CONCLUSIONS: Overall, these results suggest GLUT1 as an effective target of precision therapy, while GLUT3/4 are novel biomarkers for the prognosis of patients with BC.

An introduction of an easy-operating and economical technique for tissue microarray preparation.

AIM: Tissue microarray (TMA) is a powerful and effective tool for in situ tissue analysis. However, manual TMA construction methods showed varied qualities. This study aimed to raise a standardised TMA preparation technique that can be easily operated and is economical. METHODS: A sampling needle was used to punch the tissue rods from the donor block and holes in the recipient block. To indicate the dots' positions and ensure vertical punching, a novel auxiliary device made using commercial three-dimensional printing technology was attached. The TMA block was made up of tissue rods and a recipient block. RESULTS: A 77-rod (7×11) TMA block was constructed. The rows and columns were fixed in straight lines. There was no specimen loss during the process of embedding. CONCLUSIONS: An alternative method for the construction of TMA blocks that met the basic requirement of many laboratories and can be effortlessly performed was presented.

Human papillomavirus infection increases the risk of breast carcinoma: a large-scale systemic review and meta-analysis of case-control studies.

BACKGROUND: Breast carcinoma (BC) is a cancer with a high morbidity rate, but the mechanisms by which it develops are never clear. There has been speculation regarding the potential relationships between breast cancer and local HPV infections for some time, and although much clinical research supports this hypothesis, some research results disprove the association. Therefore, the association is still inconclusive. METHODS: We performed the data collection by searching the database PubMed, Embase, Cochrane Library and Web of science. In addition, 22 sites were added manually. After carefully selection, the pooled odds rate of 37 included case control studies was calculated. Subgroup analysis, publication bias and trim & fill analysis were conducted to make the result more reliable. RESULTS: The analysis of 37 case control studies containing 3,607 BC cases and 1,728 controls showed obviously increase of BC risk with human papillomavirus (HPV) positive [summary odds ratio (SOR) =6.22, 95% confidence interval 4.25 to 9.12; P=0.0002]. Subgroup analysis proved three high risk HPV types (HPV16, 18 and 33) were positively correlated to BC. CONCLUSIONS: This systemic review and meta-analysis provide the evidence for HPV infection as a potential risk factor in BC, while the mechanism of this hypothesis still needs further evaluation.

[Clinical experience and efficacy of endoscopic surgery for papillary thyroid microcarcinoma through total areola approach].

OBJECTIVE: To investigate the experience and efficacy of endoscopic thyroidectomy for papillary thyroid microcarcinoma (PTMC) through total areola approach.
 Methods: A total of 117 PTMC patients, who were diagnosed pathologically in Minimally Invasive Surgical Center, Second Xiangya Hospital, Central South University from June 2016 to December 2017, were divided into a endoscopic surgery group (n=72) and an open surgery group (n=45). The number of dissected central lymph nodes, blood loss, amount of drainage, occurrence of postoperative complication and recurrence were collected and compared.
 Results: Compared with the open surgery group, the blood loss was less and the operative time was longer in the endoscopic surgery group (P<0.05). There were no significant differences between the 2 groups in the number of dissected central lymph nodes, amount of drainage and occurrence of postoperative complication (all P>0.05). The mean follow-up time was more than 20 months, and there was no recurrence in the 2 groups. 
 Conclusion: Endoscopic thyroidectomy with central compartment neck dissection through total areola approach is safe and feasible in patients with PTMC. It has many advantages, such as no scar on neck, less blood loss, shorter hospital stay and more acceptable to young patients.

Targeting TRPV1 on cellular plasticity regulated by Ovol 2 and Zeb 1 in hepatocellular carcinoma.

The landscape of cellular plasticity and sources with relevant niche signals in hepatocellular carcinoma is still obscure. Transient receptor potential vanilloid 1 (TRPV1), a non-selective cation channel, is involved in a variety of malignancies and overexpressed in hepatocellular carcinoma (HCC). We have investigated the role of TRPV1 in HCC from different angles by various experimental techniques, such as in vivo and in vitro experiments, and by bioinformatics analysis of data from genetic models induced by diethylnitrosamine (DEN), mice samples and human HCC samples. We find that TRPV1 knockout promotes to hepatocarcinogenesis and deconstructs the portal triad adjacent to tumor border that is contributed by originations of tumor initiating cells and biliary cells. Epithelial to mesenchymal transition (EMT) is involved and transcription factors Ovol2 and Zeb1 coordinated with Sox 10 drive gene expression in the event which is also confirmed by the expression of these proteins in human HCC samples. Treatment with TRPV1 agonist Capsaicin inhibits the growth of HCC cells in xenograft models. Our findings demonstrate that TRPV1 is a potential therapeutic target in human HCC and exerts effects on cellular plasticity with modulation of Ovol2, Zeb1 and Sox10.

MicroRNA-153 inhibits cell proliferation, migration, invasion and epithelial-mesenchymal transition in breast cancer via direct targeting of RUNX2.

A number of microRNAs (miRNAs) are involved in the development and malignant progression of numerous types of human cancer including breast cancer. The underlying regulatory mechanism of miRNA-153 (miR-153) in breast cancer progression remains largely unknown. The present study demonstrated that miR-153 expression levels were significantly reduced in breast cancer tissue samples and cell lines, compared with adjacent healthy tissue samples and normal human breast cell line MCF-10A. In addition, low miR-153 expression was associated with advanced clinical staging and metastasis in patients with breast cancer. However, no association with age, subtype or differentiation was identified. Furthermore, patients with breast cancer with low miR-153 expression had poor prognosis, compared with patients with breast cancer with high miR-153 expression. Overexpression of miR-153 reduced proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) in breast cancer SK-BR-3 and BT-549 cells. Runt-related transcription factor 2 (RUNX2), which was revealed to be significantly upregulated in breast cancer, was verified as a target gene of miR-153 in SK-BR-3 and BT-549 cells by luciferase reporter gene assay. High RUNX2 expression was associated with advanced clinical staging as well as distant and lymph node metastasis in patients with breast cancer. However, no association with age, subtype or differentiation was identified. Additionally, an inverse correlation between miR-153 and RUNX2 mRNA expression levels was observed in breast cancer tissues. RUNX2 overexpression reduced the suppressive effects of miR-153 on the proliferation, migration, invasion and EMT of SK-BR-3 and BT-549 cells. The present study indicated that miR-153 may serve a role in breast tumor growth and metastasis via direct targeting of RUNX2. The miR-153/RUNX2 axis may be used as a potential therapeutic target in breast cancer treatment.