Objective: The proliferation and migration of hemangioma stem cells (HemSCs) induced apoptosis and adipose differentiation as well as increased the sensitivity of HemSCs to propranolol (PPNL). MiR-27a-3p negatively controlled the peroxisome-proliferator-activated receptor γ (PPAR-γ) level, counteracting the effect of PPAR-γ on HemSC progression and PPNL resistance. OMT accelerated HemSC progression and adipocyte differentiation via modulating the miR-27a-3p/PPAR-γ axis, inhibiting HemSC resistance to PPNL. In tumor-forming experiments, OMT exhibited a dose-dependent inhibitory effect on the volume of IH PPNL-resistant tumors, which was partially dependent on the regulation of m6A methylation transfer enzyme METTL3 and the miR-27a-3p/PPAR-γ axis, thereby inducing apoptosis. Conclusions: We conclude that OMT regulates IH and influences PPNL resistance via targeting the miR-27a-3p/PPAR-γ signaling pathway through m6A modification.

Due to its potential adverse effects on human health, perfluorooctanoic acid (PFOA), one of the once widely used legacy per- and polyfluoroalkyl substances (PFASs), has been recently replaced by its novel alternatives including hexafluoropropylene-oxide-dimer-acid (GenX) and ammonium 4,8-dioxa-3H-perfluorononanoate (ADONA). These alternative PFASs are detected in water and exposed workers. PFASs can enter organs like thyroids, however, it is yet unknown whether the new alternatives are safer than PFOA. In the current study, we compared the thyroid disrupting effects of PFOA and its alternatives GenX and ADONA in vitro with both rat thyroid cell line FRTL5 and primary normal human thyroid (NHT) cells. Cells were exposed to ascendant doses of PFOA, GenX or ADONA for various incubation time and cell viability was assessed by WST-1 assay and LDH assay. The proliferation rate of survived cells was determined by crystal violet-based cell proliferation assay and MTT assay. The gene expression of thyroid hormone regulation-related genes in thyroid cells after exposure was quantified by RT-PCR and Western blot. Our data showed that both PFOA and GenX reduced thyroid cell viability in both dose and time dependent manner, with GenX being more toxic than PFOA at the same condition. Similarly, the proliferation rate of cells survived exposure to PFOA and GenX was considerably impaired, with GenX showing more profound adverse effect than PFOA. Unlike PFOA and GenX, ADONA showed no apparent adverse effects on the viability and proliferation of both thyroid cell types. Gene expression data revealed that all three PFASs altered gene expression in both thyroid cells and the altered gene expression seemed to be PFAS and cell type dependent. Taken together, our data reveal that the thyroid disrupting effects is increased in the order of GenX > PFOA > ADONA. Our findings will be beneficial for the guidance of the future usage of PFASs and development of better alternatives.

目的 探讨18F-脱氧葡萄糖(18F-FDG)正电子发射计算机断层扫描(PET-CT)糖代谢参数和甲状腺癌临床病理的关系.方法 收集2015年1月～2018年12月在我院行18F-FDG PET-CT显像检查并经手术病理证实的甲状腺癌患者49例,分别对甲状腺癌灶和正常组织的最大标准摄取值(SUVmax)进行测量,分析不同病理类型及有无淋巴结转移的甲状腺癌灶的SUVmax的差异.结果 49例患者,18F-FDG PET-CT显像共检出癌灶49个.病理检查发现癌灶57个,分化型甲状腺癌38例,非分化型甲状腺癌11例;淋巴结转移22例,无淋巴结转移27例.甲状腺癌灶SUVmax为(5.39±1.42),明显高于正常甲状腺组织(1.62±0.39)(P<0.05).分化型甲状腺与非分化型甲状腺癌的SUVmax对比无统计学差异(P>0.05),有淋巴结转移与无淋巴结转移的甲状腺癌灶SUVmax对比亦无统计学差异(P>0.05).Pearson相关性分析显示,甲状腺癌灶SUVmax与病灶大小呈正相关(r=0.412,P<0.05).结论 18F-FDG PET-CT显示糖代谢增高对甲状腺癌有高度提示价值,但糖代谢水平与肿瘤病理类型及肿瘤分期可能无明显相关性.

Anaplastic thyroid cancer is a rare and aggressive disease with a dismal prognosis and an overall survival measured in months.Nearly 50％ of patients at diagnosis have locally advanced or distant metastases.Therefore,there is a lack of effective treatment.Recently,programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1),as a highly promising immune therapy,has shown good efficacy in a variety of tumors.This article aims to review biological effects,drug progression and research status of PD-1/PD-L1 in anaplastic thyroid cancer.It helps to provide some new ideas for the treatment of anaplastic thyroid cancer.

OBJECTIVE:Papillary thyroid carcinoma (PTC) is the most common type of thyroid malignancy with physiological microRNA (miR) pathomorphological changes. MiR-548c-3p participates in multiple processes of tumor development and progression. However, the role of miR-548c-3p in PTC and the underlying mechanisms remain undefined. Therefore, this study aimed to detect the expression of miR-548c-3p in PTC and to explore its exact function.MATERIALS AND METHODS:MiR-548c-3p expression was analyzed in PTC tissue and cell lines by Real-Time fluorescence quantitative Polymerase Chain Reaction. Colony formation and cell viability assay were used to measure cell proliferation. Wound healing assay and transwell invasion assay were conducted to examine cell migration and invasion. The protein expression of the signaling pathways was determined by Western blot analysis.RESULTS:Our results indicated that miR-548c-3p was downregulated in PTC tissues and cell lines. Moreover, miR-548c-3p mimics suppressed PTC cell viability, colony formation, cell migration, and invasion capacity. Low expression of miR-548c-3p significantly enhanced N-cadherin and vimentin expression. A negative correlation was determined between miR-548c-3p and hypoxia-inducible factor (HIF) 1α or vascular endothelial growth factor (VEGF) levels, indicating that miR-548c-3p inhibited tumor progression by suppressing the HIF1α-mediated VEGF signaling pathway.CONCLUSIONS:MiR-548c-3p could suppress PTC progression by inhibiting the HIF1α-mediated VEGF signaling pathway.

Thyroid cancer is the most common endocrine malignant tumor of human body.Thyroid cancer has close relationship with tumor cell surrounding immuno microenvironment in the process of formation,development,invade and metastasis.Their combined effect promotes body immune tolerance thus helps avoid from immune surveillance.Papillary thyroid cancer is the most common thyroid tumor on clinical.This article focuses on the interaction of papillary thyroid cancer and tumor cell surrounding immuno microenvironment,and the mechanism of their combined effect promotes immune evasion of tumor cells,helps to find a new approach for the diagnose and therapy of papillary thyroid cancer.

甲状腺未分化癌(anaplastic thyroid carcinoma,ATC)是来源于甲状腺滤泡细胞的实体肿瘤,虽然少见,但恶性程度高、侵袭性强、预后非常差. ATC只占甲状腺癌的1％～2％[1],平均发病年龄为70.5(38～92)岁,男女比例约为1.5∶2.0. ATC死亡病人占全部甲状腺癌的14％～39％[2]. ATC病人的中位生存时间为5.7个月,5年生存率仅5％[3]. ATC最常见的症状是迅速增大的肿块产生局部压迫症状,如声音嘶哑、吞咽困难等.近50％病人首诊时即发现远处转移,25％在随后病程中发生远处转移.最常见的转移部位为肺、骨、脑[4].

甲状腺肿瘤为人体最常见的肿瘤类型之一,其发生率逐年升高,原因可能涉及多个方面.甲状腺肿瘤的性质和病理类型多样,对其进行鉴别诊断是指导日后治疗和随访的关键.本文概要介绍数种主要的甲状腺肿瘤鉴别诊断手段,分析每种鉴别诊断手段的特点及适用范围,以期为甲状腺外科临床工作提供参考.

Papillary thyroid cancer (PTC) is one of the endocrine cancers with high clinical and genetic heterogeneity. NOTCH signaling and its downstream NOTCH-Regulated Ankyrin Repeat Protein (NRARP) have been implicated in oncogenesis of many cancers, but the roles in PTCs are less studied. In this study, we show that NRARP is frequently over-expressed in thyroid carcinoma. The over-activation of NRARP is highly and positively correlated with NOTCH genes. Moreover, we find that the expression of NRARP is highly associated with several epithelial mesenchymal transition (EMT) markers and contributes to poor survival outcomes. Therefore, these results indicate that NRARP is an important clinical biomarker in thyroid carcinoma and it promotes EMT induction as well as the progression of PTCs via NOTCH signaling activation.

Hypothyroidism is a very common hormonal deficiency and the stem cell technology which developed in the recent years may offer a therapeutic strategy for treating this disorder. Hypoxia has been demonstrated to play an important role in embryonic formation and development and to modulate stem cell differentiation. However, the influence of oxygen tension on thyroid differentiation has not been studied. In this study, we used murine induced pluripotent stem (iPS) cells for thyroid cell differentiation under normoxic and hypoxic conditions and compared differentiation efficiency in morphology, function, gene and protein expression under both conditions. We found that hypoxia promoted adhesion and outgrowth of embryoid bodies (EBs) derived from murine iPS cells. Expression of endodermal markers (Foxa2 and Gata4) and thyroid transcription factors (Pax8 and Nkx2.1) was increased by hypoxia at both gene and protein levels during early-mid differentiation stages (p<0.05). And so were the thyroid specific markers NIS and TSHR at the end of the experiment (p<0.05). In addition, functional iodide uptake by differentiated cells was also increased after hypoxia. Thyroid differentiation from iPS cells is enhanced under hypoxia and this may involve hypoxia inducible factors (HIFs) and their downstream gene FGF2. Our data offer a foundation for understanding thyroid development and provide a potentially more efficient way to use cell therapy for treating thyroid deficiency.

Background:The Notch-regulated ankyrin repeat protein (NRARP) is recently found to promote proliferation of breast cancer cells. The role of NRARP in carcinogenesis deserves extensive investigations. This study attempted to investigate the expression of NRARP in thyroid cancer tissues and assess the influence of NRARP on cell proliferation, apoptosis, cell cycle, and invasion in thyroid cancer. Methods:Thirty-four cases with thyroid cancer were collected from the Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine between 2011 and 2012. Immunohistochemistry was used to detect the level of NRARP in cancer tissues. Lentivirus carrying NRARP-shRNA (Lenti-NRARP-shRNA) was applied to down-regulate NRARP expression. Cell viability was tested after treatment with Lenti-NRARP-shRNA using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis and cell cycle distribution were determined by flow cytometry. Cell invasion was tested using Transwell invasion assay. In addition, expressions of several cell cycle-associated and apoptosis-associated proteins were examined using Western blotting after transfection. Student's t-test, one-way analysis of variance (ANOVA), or Kaplan–Meier were used to analyze the differences between two group or three groups. Results:NRARP was highly expressed in thyroid cancer tissues. Lenti-NRARP-shRNA showed significantly inhibitory activities against cell growth at a multiplicity of infection of 10 or higher (P < 0.05). Lenti-NRARP-shRNA-induced G1 arrest (BHT101: 72.57% ± 5.32%; 8305C: 75.45% ± 5.26%) by promoting p21 expression, induced apoptosis by promoting bax expression and suppressing bcl-2 expression, and inhibited cell invasion by suppressing matrix metalloproteinase-9 expression. Conclusion:Downregulation of NRARP expression exerts significant antitumor activities against cell growth and invasion of thyroid cancer, that suggests a potential role of NRARP in thyroid cancer targeted therapy.

巨大甲状腺肿在临床中并不常见，但仍有一定的发病率。因为多数为良性疾患，且不常见，所以在临床中更应予以重视。巨大甲状腺肿上极可至下颌角，下极可至胸骨后，两侧可至胸锁乳突肌后缘[1]，压迫气管、食管等引起相应症状，并使手术难度增加。本文重点讲述笔者在巨大甲状腺肿临床实践中的一些经验以及相关文献复习的体会。

通过分析在现代医学迅猛发展的背景下传统乳腺外科教学模式所暴露的弊端，阐述了循证医学的概念以及在传统乳腺外科教学模式引入循证医学教育的意义，并探讨了将循证医学引入乳腺外科的理论知识教学和临床实习带教中的具体方法，提出在乳腺外科教学中引入循证医学教育新模式是现代临床医学教育改革的切入点。

Nemo-like kinase (NLK), a serine/threonine protein kinase, has been implicated in tumor development and progression, and plays an important role in diverse signaling pathways by phosphorylating a variety of transcription factors. Recent studies demonstrated that altered expression of NLK was observed in various types of human cancers. However, the clinical significance of NLK expression in gallbladder cancer (GBC) remains largely unknown. In this study, we focused on the clinical significance of NLK in GBC, and found that nuclear NLK protein overexpression was frequently detected in GBC tissues. The overexpression of NLK was significantly correlated with histological grade, TNM stage, and perineural invasion. The results of Kaplan–Meier analysis indicated that a high expression level of NLK resulted in a significantly poorer prognosis of GBC patients ( P = 0.002). Furthermore, multivariate Cox regression analysis showed that high NLK expression was an independent prognostic factor for GBC patients (HR = 3.077). In conclusion, overexpression of NLK is closely related to progression of GBC, and NLK could be used as a potential prognostic marker for GBC patients.

[Objective] To evaluate the effects of PBL+LBL(the combination of problem-based and lecture-based learning mode) teaching mode in clinical education in China.[Method] All studies on PBL+LBL in clinical education in China published between2009-1989 were identified by searching in CNKI,VIP database,Pubmed,Cochrane library,Elsevier,and so on.Two independent assessors reviewed the studies to extract raw data.meta-analysis was performed using the RevMan 4.2 software.[Result] Five randomized controlled trials on 222 clinical students qualified for the meta-analysis according to our criteria.The students in PBL+LBL group got significant higher scores than the students in PBL group in theoretical tests(P0.05),and the students in PBL+LBL group were more satisfied with the teaching mode,too(P0.05).However,the differences of interrogation,physical examination,medical records,clinical skills and total score,between two groups were not significant(P0.05).[Conclusion] PBL+LBL mode is an effective teaching mode in clinical education in china,particularly for theory teaching,compared with PBL mode.

OBJECTIVE This study aimed to investigate the expression of B7-H4 in human thyroid cancer and determine any association with patient clinicopathological parameters and survival. METHODS B7-H4 expression in 64 clinical thyroid cancer specimens was assessed with immunohistochemistry. Moreover, B7-H4 mRNA expression in 10 fresh resected specimens were evaluated by the reverse transcription-polymerase chain reaction (RT-PCR). Immunohistochemical staining of CD3 was performed to assess the number of tumor infiltrating T lymphocytes (TILs) in thyroid cancers. RESULTS Positive B7-H4 immunohistochemical staining was observed in 61 out of 64 (95.3%) specimens of thyroid cancer tissues. Significantly more B7-H4 mRNA copies were found in thyroid cancer tissue than that adjacent normal tissue. Moreover, B7-H4 expression in human thyroid cancer tissues was significantly correlated with patient TNM stages and extrathyroidal extension (P<0.05), being inversely correlated with the number of TILs (P<0.05). The overall survival rate of the patients with higher B7-H4 expression was significantly worse than that of the patients with lower B7-H4 expression. CONCLUSIONS This present study suggests that high B7-H4 expression is associated with cancer progression, reduced tumor immunosurveillance and worse patient outcomes in human thyroid cancer.

The need of prophylactic central neck dissection (PCND) in patients with papillary thyroid carcinoma (PTC) is still controversial. The major restriction of PCND is the potential complications. We undertook a retrospective study to discuss its necessity in PTC patients.A total of 188 patients with PTC who underwent total thyroidectomy and PCND were involved. In all of these, central lymph nodes were pathologic examined. Univariate and multivariate analyses were performed based on tumor location and size, etc.Overall, node metastases were found in 44.1 % (83/188) of patients. Tumor size was the independent positive predictor for lymph node metastasis, while gender, age, tumor multifocality, tumor location, and capsular infiltration were not independent predictors of central lymph node metastases. Postoperative complications happened in 5.3 % (10/188) of patients, which 4.8 % (9/188) had temporary hypocalcemia and 0 % (0/188) had permanent hypocalcemia. Rates of temporary and permanent recurrent laryngeal nerve injury were 0.5 % (1/188) and 0 % (0/188), respectively.PCND is recommended in all patients with PTC.

Differentiated thyroid carcinoma is the most common cervical malignancy,also the most important main type of thyroid cancer. Thyroid lobectomy or total thyroidectomy is the main method for the treatment of primary tumor. Early metastasis to the central cervical lymph node usually occurs in differentiated thyroid carcinoma. Central cervical lymph node is generally considered the first station,called the"sentinel lymph node",so the central cervical lymph node dissection is particularly important in differentiated thyroid carcinoma. Patients with cN1 require the central cervical lymphadenectomy,but for patients with cN0,the need of prophylactic central neck lymphadenectomy remains controversial. This article aims to discuss the consensus and the controversy on Prophylactic Central Lymph Node Dissection applied in differentiated thyroid cancer.

Gallbladder carcinoma (GBC) is one of the mostly aggressive and fatal malignancies. However, little is known about the oncogenic genes that contributed to the development of GBC. Zinc finger X-chromosomal protein (ZFX) was a novel member of the Krueppel C2H2-type zinc-finger protein family and its down-regulation led to impaired cell growth in human laryngeal squamous cell carcinoma. Here, we aim to investigate the function of ZFX in GBC cell proliferation and migration. Loss of function analysis was performed on GBC cell line (GBC-SD) using lentivirus-mediated siRNA against ZFX. The proliferation, in vitro tumorigenesis (colony-formation) ability as well as cell migration was significantly suppressed after GBC-SD cells which were infected with ZFX-siRNA-expressing lentivirus (Lv-shZFX). Our finding suggested that ZFX promoted the growth and migration of GBC cells and could present a potential molecular target for gene therapy of GBC.