目的 探讨超声引导下细针抽吸细胞学检查(FNAC)联合BRAFV600E基因检测对甲状腺微小乳头状癌(PTMC)的术前诊断价值.方法 选取我院经手术病理确诊的PTMC患者126例,共计126个结节,按结节二维超声所测最大径分为≤5 mm组31个,5～10 mm组95个,比较两组FNAC、BRAFV600E基因检测诊断结果,分析二者联合诊断价值.结果 5～10 mm组FNAC的诊断准确率(86.32％)明显高于≤5 mm组(58.06％),两组比较差异有统计学意义(P<0.05);5～10 mm组与≤5 mm组BRAFV600E基因突变率分别为92.63％、90.32％,两组比较差异无统计学意义;FNAC联合BRAFV600E基因检测诊断≤5 mm组、5～10 mm组的准确率分别为93.54％、97.78％,均明显高于单独FNAC诊断,差异均有统计学意义(均P<0.05).结论 FNAC联合BRAFV600E基因检测可提高PTMC术前诊断准确率,且对5～10 mm PTMC诊断准确率更高.

Objective To investigate the effect of transmembrane protein 196 (TMEM196) on the migration and invasion of breast cancer cells. Methods The Cancer Genome Atlas (TCGA) and Oncomine database were used to analyze the mRNA expression of TMEM196 in breast cancer. The expression of TMEM196 in breast cancer cells was detected by quantitative real time-polymerase chain reaction (RT-qPCR). Kaplan-Meier database was employed to analyze the effect of TMEM196 on the prognosis of breast cancer patients. The protein level and prognostic effect of TMEM196 were analyzed by tissue microarray. The cohort included 70 paracancerous samples and 160 invasive breast cancer samples from the patients (53.61±13.13 years old) undergoing surgical resection from January 2001 to August 2004, with a follow-up period of 2 to 150 months. Cell proliferation experiment, scratch healing test and Transwell assay were performed to determine the effect of TMEM196 on the proliferation, migration and invasion of breast cancer cells. Western blot assay was used to explore the regulation of TMEM196 on the expression of β-catenin and matrix metalloproteinases 7 (MMP7). Results The mRNA and protein levels of TMEM196 were significantly decreased in breast cancer (P < 0.05), and notably, this phenomenon was most obvious in triple negative breast cancer (TNBC) cell line MDA-MB-231 and TNBC tissues (P < 0.05). Lower expression of TMEM196 was associated with poor overall survival (OS) (HR=0.524, 95%CI: 0.293~0.936, P=0.040). In addition, overexpression of TMEM196 could significantly inhibit the proliferation, migration and invasion of breast cancer cells(P < 0.05), while its knockdown can significantly enhances the above abilities(P < 0.05). The results of Western blot assay indicated that TMEM196 inhibited the β-catenin/MMP7 signaling pathway and reduced the motility of breast cancer cells(P < 0.05). On the contrary, the tumor-promoting effect which caused by knockdown of TMEM196 could be eliminated after adding β-catenin inhibitor(P < 0.05). Conclusion TMEM196 inhibits the migration and invasion of breast cancer cells by regulating the β-catenin/MMP7 signaling pathway.

Objective:To analyze the immune implication of NR3C2 gene in breast cancer using bioinformatics methods and construct a prognostic model.Methods:(1) The breast cancer cohort in the Cancer Genome Atlas (TCGA) database and the GSE42568 cohort in the Gene Expression Omnibus (GEO) database were used as training set (113 paracancerous samples and 1 019 breast cancer samples) and testing set (17 paracancerous samples and 104 breast cancer samples), respectively. The mRNA level of NR3C2 was compared between adjacent tissue and tumor tissue samples in the above 2 cohorts. The effect of NR3C2 expression on recurrence-free survival (RFS) was analyzed in cohorts of TCGA and Kaplan-Meier plotter(4 929 breast cancer samples), respectively. (2) The Gene Set Enrichment Analysis (GSEA) was employed to explore the potential biological functions of NR3C2. The 24 immune cells were quantitively accessed by single sample gene set enrichment analysis (ssGSEA) and the correlation of NR3C2 with 24 immune cells and 70 immunomodulator genes were conducted by Pearson coefficient. (3) A prognostic model was constructed by NR3C2-related immunomodulator genes in the TCGA cohort through multivariate stepwise Cox regression. The TCGA cohort was divided into two groups (high-risk group and low-risk group) by median risk value and RFS was compared between two groups. The sensitivity and specificity of the model was calculated using receiver operating characteristic (ROC) curves and validated in the GSE42568 cohort. Combined with other clinical parameters, the independent prognostic performance of this model was analyzed by multivariate Cox regression. (4) A nomogram was constructed based on pathological stage and risk value in TCGA cohort. The calibration curve was used to evaluate its accuracy and the predictive accuracy of different parameters was compared by time-dependent area under curve (tAUC). (5) In order to verify whether the NR3C2 mRNA expression is consistent with NR3C2 protein expression, we collected clinical specimens from three breast cancer patients who underwent surgical resection in the Department of Breast and Thyroid Surgery of the Army Medical Center in September 2021. The protein expression of NR3C2 in the paracancerous tissue and cancer tissue was detected by Western blot analysis.Results:(1) In TCGA cohort, the mRNA expression of NR3C2 in breast cancer tissue was significantly lower than that in paracancerous tissues (2.59±0.43 vs 0.98±0.62, t=35.990, P<0.001). In GSE42568 cohort, the mRNA expression of NR3C2 in breast cancer tissue was significantly lower than that in paracancerous tissues (5.35±1.47 vs 3.32±1.12, t=7.096, P<0.001). The results of survival analysis showed that in TCGA cohort and Kaplan-Meier plotter cohort, NR3C2 expression was positively correlated with RFS in breast cancer patients (HR=0.667, 0.725; 95%CI: 0.458-0.972, 0.653-0.804; both P<0.050). (2) GSEA results suggested that NR3C2 was mostly involved in JAK-STAT and TGF-β signaling pathways related to immunity. Correlation analysis found that the mRNA expression of NR3C2 was significantly correlated with 19 immune cells and 43 immunomodulator genes (all P<0.050). (3) The 43 NR3C2-related immunomodulator genes were included in Cox regression to construct a prognostic model which composed of 13 immunomodulator genes with a risk cutoff value equal to 0.988. Survival analysis showed that in TCGA cohort and GSE42568 cohort, the RFS in high-risk group was significantly lower than that in low-risk group (HR=2.682, 2.389; 95%CI: 1.839-3.910, 1.343-4.248; both P<0.010). ROC indicated that the AUC was 0.758 and 0.618 in TCGA cohort and GSE42568 cohort, respectively (95%CI: 0.662-0.857, 0.545-0.758; sensitivity: 0.833, 0.538; specificity: 0.614, 0.714; both P<0.010). Multivariate Cox regression showed that the risk score of this model could serve as an independent prognostic factor for breast cancer in TCGA cohort and GSE42568 cohort (HR=1.259, 1.163; 95%CI: 1.187-1.336, 1.068-1.266; both P<0.001). (4) The nomogram constructed based on the pathological stage and risk value could predict the 3-year, 5-year and 8-year RFS of breast cancer patients. The calibration curve suggested that it has good predictive accuracy and tAUC indicated that it is superior to pathological stage and a prognostic model. (5) Western blot analysis showed that the protein expression of NR3C2 was significantly decreased in breast cancer tissues.Conclusion:NR3C2 is a potential immunotherapeutic target and prognostic biomarker in breast cancer patients.

目的 探讨超声引导下细针抽吸细胞学检查（FNAC）联合BRAF V600E 基因检测对甲状腺微小乳头状癌（PTMC）的术前诊断价值。方法 选取我院经手术病理确诊的PTMC患者126例，共计126个结节，按结节二维超声所测最大径分为≤5 mm组31个，5～10 mm组95个，比较两组FNAC、BRAF V600E 基因检测诊断结果，分析二者联合诊断价值。结果 5～10 mm组FNAC的诊断准确率（86.32%）明显高于≤5 mm组（58.06%），两组比较差异有统计学意义（P＜0.05）;5～10 mm组与≤5 mm组BRAF V600E 基因突变率分别为92.63%、90.32%，两组比较差异无统计学意义；FNAC联合BRAF V600E 基因检测诊断≤5 mm组、5～10 mm组的准确率分别为93.54%、97.78%，均明显高于单独FNAC诊断，差异均有统计学意义（均P＜0.05）。结论 FNAC联合BRAF V600E 基因检测可提高PTMC术前诊断准确率，且对5～10 mm PTMC诊断准确率更高。

目的:探讨吲哚菁绿荧光显影在经口腔前庭入路机器人甲状腺手术中对甲状旁腺保护的可行性.方法:18例患者行经口腔前庭入路机器人甲状腺手术,女性17例,男性1例,平均年龄(45.78±11.64)岁,平均肿瘤直径(0.97±0.50)cm,术中静脉推注吲哚菁绿识别甲状旁腺及其血供.对患者术前及术后血清甲状旁腺素(Parathyroid hormone,PTH)和血清钙离子浓度水平、术中清扫淋巴结数目及并发症情况等进行分析.结果:18例患者均实施甲状腺癌根治术,术中均可见荧光显影的甲状旁腺,平均清扫淋巴结数目(8.67±6.41)枚,术后病理结果均提示甲状腺乳头状癌,并有部分淋巴结转移.术后2例患者出现一过性甲状旁腺功能低下,无1例患者出现永久性甲状旁腺功能低下及由此引起的低钙血症,术后无患者出现暂时性或永久性喉返神经(Recurrent laryngeal nerve,RLN)损伤.所有患者术后恢复良好,无其他并发症.结论:在机器人荧光显影模式下,通过静脉注射吲哚菁绿荧光显影技术避免甲状旁腺意外损伤是安全、可行的,由于本研究纳入患者例数较少,仍需进一步行临床试验证实其安全性和有效性.

目的:通过分析29例经口腔前庭入路达芬奇机器人甲状腺切除术(transoral robotic thyroidectomy vestibular approach,TORTVA)的临床疗效,总结经口腔前庭入路机器人甲状腺手术的初步经验.方法:回顾性分析2017年12月至2021年2月共29例在陆军特色医学中心乳腺甲状腺外科接受TORTVA患者的病例资料,分析其临床病理特征、手术方式及时间、术后并发症及住院时间等.结果:29例患者中,女性25例,男性4例;平均年龄(36.31±8.30)岁,平均肿瘤大小(1.07±0.73)cm.其中25例甲状腺乳头状癌,4例甲状腺良性病变.行单侧甲状腺部分切除术3例,单侧甲状腺腺叶切除术1例,单侧甲状腺次全切除加中央区淋巴结清扫(central neck dissection,CND)2例,单侧甲状腺腺叶及峡部切除加CND 22例,甲状腺次全切除1例.平均手术时间(253.10±51.55)min.平均清扫淋巴结数目(5.72±4.12)枚.术后未出现暂时性或永久性喉返神经损伤和低钙血症,9例患者术后发生颏神经暂时性麻痹.术后平均住院时间(2.48±0.97)d,平均随访时间(11.40±11.08)月,均未出现复发或转移.结论:通过严格把握手术适应症,TORTVA是安全可行的,但远期疗效仍有待进一步观察.

近年来,甲状腺疾病的发病率逐年上升,其中青年女性患者占较大比例.随着年轻患者对美容的要求提高,多种入路的内镜甲状腺手术已广泛成功开展.这些术式尽管避免了在颈部做切口,并取得了较好的美容效果,但不可避免地在其他部位留下切口瘢痕.经口入路手术被认为是真正无痕的手术,具有更好的美容效果,随着近年来达芬奇手术系统的不断完善,经口入路机器人甲状腺手术也取得较大发展.与其他术式相比,经口入路机器人甲状腺手术具有多种优势,如提供中线入路、最低程度地减少组织损伤、3D高清放大视野、手臂震颤过滤及7个自由度Endo-wrist等.因此,本综述对近年来经口机器人甲状腺手术的研究进展进行总结,为临床甲状腺疾病的治疗提供学习借鉴.