Long non-coding RNA(lncRNA) is non-protein coding transcripts longer than 200 nucleotides,which plays an important role in the development of the metabolic process.Thyroid cancer is the most common cancer of the endocrine system,and as reported,lncRNA is related to the occurrence and development of thyroid tumors.Therefore,this paper reports the latest domestic and foreign research progress about lncRNA in thyroid tumor,in order to provide new ideas for molecular diagnosis and treatment of thyroid cancer.

[ABSTRACT]OBJECTIVETo study the expressions of 34βE12, Galectin-3 and HBME-1 in thyroid nodules, and to explore its diagnostic value for papillary thyroid carcinoma (PTC).METHODSEn VisionTM immunohistochemical technique was used to detect the expression of 34βE12, Galectin-3 and HBME-1 in 352 thyroid lesions. The correlation between the expressions of the 3 protein markers and clinicopathological characteristics was evaluated. The receiver operating characteristic area under the curve (ROC-AUC) and their index for diagnosis evaluation were also calculated.RESULTSThe positive rates of 34βE12, Galectin-3 and HBME-1 in 246 PTC lesions were significantly higher than those in benign nodules (P<0.001). There was no relationship between the expression of the 3 protein markers and clinicopathological characteristics (eg. gender, age, numbers of lesions, tumor size, capsular invasion, lymph node metastasis, TNM staging). The ROC-AUC of 34βE12, Galectin-3 and HBME-1 for diagnosis of PTC was 0.936, 0.915 and 0.898 respectively. The sensitivity of 34βE12, Galectin-3 and HBME-1 for diagnosis of PTC was 94.3%, 95.5% and 91.1% respectively, while the specificity was 81.1%, 71.7% and 83.0% respectively, and the diagnostic accuracy rate was 90.3%, 88.4% and 88.6% respectively.CONCLUSION The expressions of 34βE12, Galectin-3 and HBME-1 are statistically different between PTC and benign lesions, but no associations are found with clinicopathological characteristics, indicating the three protein markers have important diagnostic value for PTC.

OBJECTIVE The objective of this study is to discuss when to dissect the lymph nodes behind the right recurrent laryngeal nerve (LN-prRLN) from the standpoint of the right cervical level Ⅵ-1 (superficial layer to the recurrent laryngeal nerve) lymph nodes in papillary thyroid carcinoma (PTC) patients.METHODS The clinical data of 306 bilateral or right PTC patients from the Hangzhou First People's Hospital who underwent dissection of level Ⅵ-1 lymph nodes and LN-prRLN between March 2014 and September 2015 were analyzed. We measured the number of level Ⅵ-1 metastatic lymph nodes and size of level Ⅵ-1 lymph nodes metastasis loci to predict the metastasis of LN-prRLN.RESULTS The number of level Ⅵ-1 metastatic lymph nodes and size of level Ⅵ-1 lymph nodes metastasis loci were risk factors of LN-prRLN metastasis(P<0.05). When the number of the level Ⅵ-1 metastatic lymph nodes was greater than 1.5, the AUC was 0.813 (the sensitivity was 78.43%, the specificity was 76.65%). The ROC showed that when the size of level Ⅵ-1 lymph nodes metastasis loci were more than 0.45 cm, the AUC was 0.726 (sensitivity was 90.20%, specificity was 48.90%).CONCLUSION In bilateral or right PTC patients with metastasis of level Ⅵ-1 lymph nodes, especially when the number of level Ⅵ-1 metastatic lymph nodes was greater than 2cm and the metastasis loci were more than 0.45 cm, we should dissect the LN-prRLN.

Objective To compare lateral orbital keyhole approach(LOK) with conventional keyhole approach including supraorbital keyhole approach (SOK) and pterional approach(PTK) for exposuring the sellar region and oper-ation ability, to provide theoretical and practical basis for the clinic. Methods From January, 2017 to Feburary, 2018, 15 cadaver head specimens of Chinese (30 sides) fixed by formalin were randomly divided into 3 groups, simu-lating SOK, LOK and PTK, application of frameless neuronavigation system, intersection of the posterior margin of the optic chiasma and the lamina terminalis served as the base point. Six different reference points were selected to radi-ate into the parasellar region of the skull base. The direction of the 2 adjacent reference points were connected to the base point to form a triangle. Six triangles constituted the sellar region to represent the total area. The supratentorial area, ipsilateral area, inferior area and contralateral area were calculated by stacking triangle. The comparison was made between groups. The Salma operation exposure scale was used to simulate the aneurysms of the common parts in the brain and the quantitative scores were performed. Results The total parasellar regions by SOK, LOK and PTK respectively were:(1641.6±295.6)mm2, (1782.3±294.6)mm2 and (1552.5±307.4)mm2. There was no statistical differ-ence(P>0.05); To compare the supratentorial region, SOK and LOK were both bigger than PTK ( P<0.05); To compare the ipsilateral and infratentorial area, LOK and PTK were both bigger than SOK respectively ( P<0.05);To compare the contralateral area, SOK, LOK and PTK were increased in turn (P<0.05). Salma operation exposure scale was used to get the scores:the score of SOK was 29.7 (39.08％), LOK was 37.0 (48.68％), and PTK was 36.1 (47.50％). Conclusion Anatomical analysis displayed that the 3 keyhole approaches showed different exposure of each part the parasellar re-gions, the LOK had a good exposure to the parasellar region and so as the higher maneuverability. But the clinical appli-cation should be comprehensive analysis, pay attention to specific lesions and make an appropriate choice. It has impor-tant clinical significance to improve the prognosis of patients.

OBJECTIVE To investigate the clinical value of the lymph nodes posterior to the right recurrent laryngeal nerve (LN-prRLN, right VI-2) dissection in papillary thyroid carcinoma (PTC). METHODS We studied the relationships between LN-prRLN metastasis and the clinicopathological characteristics in 408 patients with right or bilateral PTC who underwent LN-prRLN dissection. RESULTS Right VI-2 lymph node metastasis was 16.67％. Single factor analysis showed that there were statistically significant correlations between right VI-2 metastasis and gender, age, size and number of right thyroid lobe tumor, capsular invasion, right VI-1 lymph node metastasis and their size, and also metastatic lymph node in the right cervical lateral compartment. Multivariate Logistic regression analysis showed that Right VI-2 lymph node metastasis was related to right tumor size, capsular invasion, the right VI-1 metastasis and right lateral lymph node metastasis(P＜0.05). The receiver-operator characteristic (ROC) analysis showed that the risk factors of LN-prRLN: age ＜35.5 years, right tumor size ＞0.85 cm, lymph node (right VI-1) number ＞1.5, metastatic lymph node (right VI-1) size ＞0.45 cm, lymph node number in the right cervical lateral compartment ＞0.5 and the areas under the ROC curves were 0.585, 0.787, 0.788, 0.725, 0.719. CONCLUSION The dissection of LN-prRLN should be considered when patient with the risk factors such as male, age ＜35.5 years, right tumor size ＞0.85 cm, capsular invasion, lymph node (right VI-1) number ＞1.5, metastatic lymph node (right VI-1) size ＞0.45 cm, lymph node number in the right cervical lateral compartment ＞0.5.

Objective To investigate the relationship between Hashimoto thyroiditis (HT) and thyroid papillary carcinoma (PTC) by analyzing the expression of BRAF V600E mutation and (N-,H-,K-) RAS codons 12,13 and 61 mutants in cases of multifocal PTC with HT.Methods 80 tumor samples in 37 multifocal PTC with HT cases,were analyzed for the genotypic changes of BRAF V600E,as well as the (N-,H-,K-)RAS codons 12,13 and 61 mutants by DNA sequencing assay and amplification refractory mutation system (ARMS).Results BRAF V600E mutation was detected in 51 samples and RAS gene mutations was found in 3 samples (N-RAS codon 61 mutant in 2 samples and H-RAS codon 61 mutant in 1 sample).Different clonal origin was present in 20 cases of multifocal PTC with HT (54.1％,20/37).There was no statistical significance (P ＞ 0.05) in the incidence of the difference in the origin of tumor cells,compared with the results (61.7％,37/60) of multifocal PTC without HT in the related literature.Conclusion In more than half of multifocal PTC with HT cases,the tumor cells originate from different clones.Our results do not support the opinion that HT predisposes patients to develop PTC,because HT does not have a significant effect on expression of BRAF and RAS gene mutation in PTC,accordingly HT is more likely to be a part of the host tumor immune response system.

Objective:To investigate the efficacy and clinical experiences of fluorescein angiography assisted occlusion via lateral-orbital keyhole approach in internal carotid bifurcation aneurysms. Methods:The clinical data of 16 patients with internal carotid artery bifurcation aneurysms admitted to our hospital from January 2016 to December 2020 were retrospectively analyzed. All patients accepted fluorescein angiography assisted occlusion via lateral-orbital keyhole approach. The patients were followed up at one, 3, and 6 months after surgery by medical imaging. The therapeutic efficacy of these patients was assessed by Glasgow outcome scale (GOS). Results:All aneurysms in these 16 patients were clipped at one-stage operation. Intraoperative fluorescein angiography and FLOW 800 showed that the aneurysms were completely clipped without residual, and the blood flow of the parent artery and perforating arteries was unobstructed. Six months after surgery, 14 patients recovered well (GOS scores of 5), and 3 developed limb hemiplegia (GOS scores of 4).Conclusion:Intraoperative fluorescein angiography assisted occlusion via lateral-orbital keyhole approach is safe and effective in internal carotid bifurcation aneurysms.

Objective To investigate the hemodynamic monitoring and clinical significance of transcranial Doppler (TCD) combined with indocyanine green (ICG) fluorescence angiography and FLOW 800 in carotid endarterectomy (CEA).Methods Forty-eight patients with extracranial carotid atherosclerotic stenosis underwent CEA in our hospital from October 2015 to September 2018 were chosen to our study. The mean blood flow velocity (Vm) of the middle cerebral artery (MCA) was monitored by TCD throughout the operation. The intraoperative blood pressures were adjusted according to the monitoring results, and the average blood Vm of the narrowed arteries was measured using TCD probe before and after artery temporary occlusion. ICG fluorescence angiography and FLOW 800 were used to monitor vascular morphology and patency simultaneously.Results One patient, who was observed to have severe stenosis by TCD, ICG fluorescence angiography, and FLOW 800 after arteries temporary occlusion, showed significantly improved by multimodal monitoring after re-suture; one patient showed external carotid artery occlusion by ICG fluorescence angiography and FLOW 800 had noexternal carotid artery occlusion; other 46 patients showed no carotid artery stenosis and good intracranial perfusion by TCD, ICG fluorescence angiography, and FLOW 800 after initial suture. Two patients developed ischemic stroke (IS) after CEA, and both of them were recovered after conservative medical treatment for two weeks without any neurological dysfunction; two patients had cerebral hyperperfusion syndrome (CHS), and both of them relieved after blood pressure control three d after treatment; one patient had subcutaneous hematoma in the operation area, and the hematoma was gradually absorbed after conservative treatment; the rest patients recovered well. All patients were followed up for 4-6 months after CEA, and CT angiography showed that carotid artery stenosis was relieved; CT perfusion imaging and TCD examinations showed that cerebral perfusion was significantly improved as compared with those before operation.Conclusion Intraoperative TCD combined with ICG fluorescence angiography and FLOW 800 can effectively monitor the intracranial and extracranial blood flow of intraoperative carotid artery, which is of great significance in reducing the risk of IS and CHS during carotid endarterectomy.

OBJECTIVE To explore the feasibility of detection for mutated BRAF V600E gene based on amplification refractory mutation system(ARMS),and to evaluate its clinical significance of BRAF V600E gene mutation in thyroid nodules.METHODS The method of ARMS was used to detect BRAF V600E mutation status in 179 patients with PTC and 115 patients with benign lesions.The diagnosis index of BRAF V600E mutation status for identifying the nature of the thyroid nodule was calculated.The potential correlation between BRAF V600E mutation and PTC clinicpathological characteristics was also analyzed.RESULTS Detection of BRAF V600E mutation status in thyroid lesions based on ARMS was feasible and believable.The positive rate of mutated BRAF V600E gene in PTC was 82.68％,whereas the rate in benign lesions was only 1.74％,indicating statistical differences between the two groups(x2=183.568,P＜0.01).The diagnostic sensitivity of BRAF V600E mutation was 82.68％,specificity was 98.26％,accuracy was 88.76％,and Youden index was 0.8094.There was no associations between the BRAF V600E mutation status and PTC clinicpathological characteristics(eg.gender,age,tumor size,numbers of lesions,bilateral lesions,extrathyroidal extension and lymph node metastasis).CONCLUSION Detection of BRAF V600E mutation based on ARMS has higher sensitivity and specificity in distinguishing PTC from benign lesions,indicating BRAF V600E gene is an ideal marker of PTC for clinical early diagnosis.

The CD19-targeting bispecific T-cell engager blinatumomab has shown remarkable efficacy in patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia. However, several studies showed that blinatumomab has a short plasma half-life due to its low molecular weight, and thus its clinical use is limited. Furthermore, multiple trials have shown that approximately 30% of blinatumomab-relapsed cases are characterized by CD19 negative leukemic cells. Here, we design and characterize two novel antibodies, A-319 and A-2019. Blinatumomab and A-319 are CD3/CD19 bispecific antibodies with different molecular sizes and structures, and A-2019 is a novel CD3/CD19/CD20 trispecific antibody with an additional anti-CD20 function. Our in vitro, ex vivo, and in vivo experiments demonstrated that A-319 and A-2019 are potent antitumor agents and capable of recruiting CD3 positive T cells, enhancing T-cell function, mediating B-cell depletion, and eventually inhibiting tumor growth in Raji xenograft models. The two molecules are complementary in terms of efficacy and specificity profile. The activity of A-319 demonstrated superior to that of A-2019, whereas A-2019 has an additional capability to target CD20 in cells missing CD19, suggesting its potential function against CD19 weak or negative CD20 positive leukemic cells.
Antigens, CD19/therapeutic use* ; Antineoplastic Agents/pharmacology* ; Humans ; Immunotherapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; T-Lymphocytes