Background Thyroid autoantibody is a marker for the diagnosis of Hashimoto's thyroiditis(HT),and B cells are essential in the pathogenesis of HT.Enhancer of Zeste homolog 2(EZH2),which is an important epigenetic regulator,plays an important role in the regulation of lymphocytes development and function.Objective To investigate EZH2 expression in plasmoblasts and plasma cells in HT,and further explore the therapeutic effect of EZH2 inhibitors in experimental autoimmune thyroiditis(EAT)model.Methods The thyroid tissues from 6 patients who underwent thyroidectomy(3 HT patients with PTC,3 patients with PTC alone)in Peking University First Hospital between 2010 and 2020 were obtained from the contralateral lobe with thyroid cancer,and screened for the expression of B-lymphocyte-related genes by RNA-seq;thyroid tissues from 16 HT patients and 8 normal thyroid tissues were collected and verified for the the expression of EZH2 in B cells in HT thyroid tissues by immunohistochemistry or immunofluorescence,respectively.Fine-needle aspiration(FNA)samples from patients with HT(n=25),and peripheral blood from patients with HT(n=19)or healthy donors(n=12)were analyzed by flow cytometry to define altered EZH2 expression in plasmablasts and plasma cells.Fifteen seven-week-old NOD.H-2h4 mice were randomly divided into the control(n=5),EAT without injection group(n=5),and EZH2 inhibitor+ GSK126 injection group(10 mg/kg,intraperitoneal injection 3 times/week,n=5).The degree of thyroid inflammation and changes in TgAb levels were observed after 8 weeks.Results RNA sequencing analysis showed that EZH2 and genes associated with the B-cell phenotype such as CD19,CD27,CD38,CD52 were higher expressed in HT hyroid tissues compared with normal thyroid tissues.Immunohistochemical results showed that immunohistochemical staining for EZH2 in 16 HT thyroid tissue specimens was strongly positive with positive cells observed in the GC region,and no positive cells were observed in the staining of 8 normal thyroid tissues.EZH2 staining in HT thyroid tissue was highly expressed in the GC region,and EZH2 was specifically expressed in CD19+ B cells.The results of flow cytometry assay showed that the proportion of CD19+ B cells,plasmablasts and plasma cells in HT FNA samples was higher than that of HD peripheral blood and HT peripheral blood samples(P<0.01),and the proportion of EZH2 positivity in CD19+ B cells and plasma cells was higher in HT FNA samples than that of HT peripheral blood(P<0.005).In the mouse experiments,lymphocytic infiltration of the thyroid tissues was increased in the EAT group compared to the control group.In the GSK126 treatment groups,the thyroid inflammatory score and serum TgAb titer were significantly higher than the control group and lower than the EAT group.Conclusion EZH2 over-expression in CD19+ B cells of HT hyroid tissues may promote the differentiation of B cells into plasma cells and auto-antibody production,which leads to the destruction of thyroid tissues.EZH2 inhibitors can slow down the degree of thyroid inflammation in the EAT model.Increased EZH2 expression in plasmablasts may be involved in the pathogenesis of HT.EZH2 may serve as a therapeutic target for HT,although further studies are needed.

目的 探讨Kwak TI-RADS与ACR TI-RADS对儿童甲状腺结节的诊断效能及应用价值.方法 回顾性分析68个儿童甲状腺结节,构建受试者工作特性曲线(ROC),分析ACR TI-RADS和Kwak TI-RADS对儿童甲状腺结节的应用价值.结果 两种分类方法恶性度均随分类级别增加而增高,以Kwak TI-RADS 4b类和ACR TI-RADS 4类为最佳诊断点,Kwak TI-RADS的特异度略高于ACR TI-RADS(54.5％:51.5％,P<0.05),但两者灵敏度、PPV、NPV、AUC均无统计学意义(P>0.05);按照ACR TI-RADS成人推荐甲状腺结节穿刺标准,28％(7/25)儿童恶性结节没有分入建议穿刺组.结论 Kwak TI-RADS和ACR TI-RADS对儿童甲状腺结节分类均具有较好的指导作用,Kwak TI-RADS具有相对较高特异度,但儿童甲状腺结节在应用ACR TI-RADS推荐的穿刺标准尚需进一步研究.

Long non-coding RNA( lncRNA) (>200 nt) is a non-coding RNAS ( ncRNA) which play an important role in cells differentiation proliferation apoptosis and cancer development. LncRNAs also have functions in the development of mucocutaneous diseases. In this paper we reviewed the relationship between lncRNA and the mucocutaneous diseases.