甲状腺乳头状癌伴发桥本甲状腺炎的临床研究

背景与目的：甲状腺乳头状癌（papillary thyroid carcinoma，PTC）和桥本甲状腺炎（Hashimoto’s thyroiditis，HT）的发病率均呈上升趋势，两者之间的关系已成为目前研究的热点。探讨PTC和HT之间的关系。方法：回顾性分析2014—2015年期间在中国科学院大学附属肿瘤医院头颈肿瘤外科行甲状腺癌手术治疗的首诊患者306例，术后病理学检查均明确诊断为PTC，其中术后病理学确诊伴发HT者42例，比较伴发HT与未伴发HT患者的临床病理学特征。结果：PTC患者女性发病年龄高于男性（46.2岁 vs 41.9岁）。相较于与未伴发HT的PTC患者，伴发HT的患者中女性比例更高（93% vs77%），中央区淋巴结数目较多［（5.0±3.4）枚 vs （2.5±2.7）枚］，术前促甲状腺激素（thyroid-stimulating hormone，TSH）水平较高［（3.28±1.91）μU/mL vs （2.12±1.29）μU/mL］，术前抗甲状腺过氧化物酶抗体（thyroid peroxidaseantibody，TPOAb）阳性率较高（55% vs 14%），术前甲状腺球蛋白抗体（thyroglobulin antibodies，TgAb）阳性率较高（69% vs 13%）。发生中央区淋巴结转移的患者中，中央区淋巴结转移数目与中央区淋巴结总数显著相关（Pearson相关系数=0.582）。多因素logistic回归分析发现，男性、低龄、被膜侵犯是PTC患者中央区淋巴结转移的独立危险因素。结论：伴发HT对PTC患者的预后无显著影响。伴发HT的PTC患者TSH水平显著偏高，提示HT可能是PTC发病风险因素之一。中央区淋巴结转移数目与中央区淋巴结总数相关，推测PTC淋巴结转移可能与淋巴结炎症反应相关。     

天麻钩藤饮联合甲泼尼龙治疗桥本脑病临床观察

目的:观察天麻钩藤饮联合甲泼尼龙治疗桥本脑病的临床效果。方法:26例随机分为治疗组和对照组各13例,两组均用甲泼尼龙治疗,治疗组加用天麻钩藤饮治疗。结果:WAIS-R评分操作量表分、WMS-R评分量表分治疗组均低于对照组(P<0.05),日常生活能力量表(ADL)评分治疗组高于对照组(P<0.05)。结论:天麻钩藤饮联合甲泼尼龙治疗桥本脑病可改善临床症状,减轻不良反应,优于单用西药治疗。     

亚急性甲状腺炎超声特征与中医证型相关性评价

目的:探讨亚急性甲状腺炎超声特征与中医证型的相关性。方法:将甲状腺穿刺活检确诊为亚急性甲状腺炎的65例患者纳入研究,对患者实施中医辨证和超声(超声弹性成像)检查,观察不同中医证型患者的超声表现,并对患者的超声检查图像进行分级,比较不同超声分级患者的中医证型。结果:中医证型以风热痰凝证为主,风热痰凝证与肝郁气虚证比较,差异有统计学意义(χ^2=4.680,P=0.031)。风热痰凝证与气阴两虚兼痰凝证比较,差异有统计学意义(χ^2=8.613,P=0.003)。患者主要超声表现包括甲状腺肿大、片状低回声区、低回声区周围有丰富血流信号、甲状腺上动脉峰值流速>40 cm/s。风热痰凝证各超声表现与气阴两虚兼痰凝证比较,差异有统计学意义(P <0.05);风热痰凝证甲状腺肿大、片状低回声区与肝郁气虚证比较,差异有统计学意义(P <0.05)。风热痰凝证各超声表现(除甲状腺肿大外)与气阴两虚兼痰凝证比较,差异有统计学意义(P <0.05)。超声弹性成像分级Ⅱ级构成比与0级比较,差异有统计学意义(χ^2=15.577,P=0.000);Ⅱ级构成比与Ⅰ级比较,差异有统计学意义(χ^2=5.969,P=0.015);Ⅱ级构成比与Ⅲ级比较,差异无统计学意义(χ^2=1.851,P=0.174);Ⅱ级构成比与Ⅳ级比较,差异无统计学意义(χ^2=2.459,P=0.117)。不同超声弹性成像分级中医证型分布情况比较,0级:风热痰凝证与肝郁气虚证比较,差异有统计学意义(χ^2=4.800,P=0.028);Ⅱ级:风热痰凝证与肝郁气虚证、气阴两虚兼痰凝证比较,差异有统计学意义(χ^2=7.765,6.017,P=0.005,0.014);Ⅳ级:风热痰凝证与肝郁气虚证、气阴两虚兼痰凝证比较,差异有统计学意义(χ^2=7.337,5.250,P=0.007,0.022);其他证型两两比较,差异无统计学意义(P> 0.05)。结论:亚急性甲状腺炎患者的超声特征与中医证型存在密切联系,不同中医证型患者的超声表现存在明显差异,不同超声弹性成像分级患者的中医证型分布也存在明显差异,而超声弹性成像分级更高。     

等离子射频辅助双侧声带后端切断术治疗双侧声带麻痹导致的上气道梗阻患者13例

目的 评估内镜下等离子射频辅助双侧声带后端切断术治疗双侧声带麻痹导致上气道梗阻患者的疗效。 方法 回顾性分析13例双侧声带麻痹导致的上气道梗阻患者的病例资料,其中男6例、女7例,27~73岁,所有患者均接受等离子射频辅助双侧声带后端切断术。总结评估该手术的临床疗效。 结果 13例随访时间1年1个月~2年11个月,所有患者无严重并发症发生。一次拔管率为84.44%(10/13),二次手术拔管率为88.89%(11/13),拔管时间1~3个月,中位数1个月,上气道梗阻均未复发。 结论 内镜下等离子射频辅助双侧声带切断术操作简单、手术风险小,同时治疗双侧声带麻痹效果可靠,是双侧声带麻痹导致上气道梗阻的有效治疗方法之一,也可作为其他治疗失败的补救治疗措施。     

Chronic lymphocytic thyroiditis protects against recurrence in patients with cN0 papillary thyroid cancer

BackgroundChronic lymphocytic thyroiditis (CLT) frequently coexists with papillary thyroid carcinoma (PTC) that exhibits normal thyroid function. However, few studies have investigated the relationship between CLT and clinically lymph node (LN)-negative PTC. The aim of this study was to evaluate the relationship between subclinical central LN metastasis and CLT, and to assess the impact of CLT on the recurrence of clinically LN-negative PTC.MethodsWe investigated the medical records of 850 patients with PTC who underwent prophylactic bilateral central neck dissection as well as total thyroidectomy between 2004 and 2010; the median follow-up time was 95.5 months (range, 12–158 months).ResultsCLT was observed in 480 patients (56.5%). Female sex, a preoperative thyroid-stimulating hormone level >2.5 mU/L, a primary tumor ≤1 cm, no gross extrathyroidal extension, high number of harvested LNs, low number of metastatic LNs, and positive anti-thyroglobulin (Tg) antibody at 1 year post-initial treatment were significantly associated with the presence of CLT. Multivariate analysis revealed that patients with N1a stage (vs. N0 stage; hazard ratio [HR], 3.255; 95% confidence interval [CI], 1.290–8.213; p = 0.012) and positive anti-Tg antibody at 1 year post-initial treatment (vs. negative anti-Tg antibody; HR, 5.118; 95% CI, 2.130–12.296; p < 0.001) had poorer recurrence-free survival (RFS), while those with CLT (vs. no CLT; HR, 0.357; 95% CI, 0.157–0.812; p = 0.014) had favorable RFS outcomes.ConclusionsCLT is associated with less aggressive tumor characteristics and LN metastasis. Clinically LN-negative PTC patients with CLT experience longer RFS intervals than those without CLT.     

小金胶囊联合左甲状腺素钠片治疗桥本氏甲状腺炎的临床研究

目的:探讨小金胶囊联合左甲状腺素钠片治疗桥本氏甲状腺炎的临床研究。方法:选取2017年8月—2019年1月收治的桥本氏甲状腺炎患者106例,按照数字表法将其随机分为两组,对照组应用左甲状腺素钠片治疗,研究组应用小金胶囊联合左甲状腺素钠片治疗,对两组患者临床疗效、甲状腺功能及炎症反应等指标进行分析。结果:研究组的临床治愈比例高于对照组(50.9%vs 18.7%);研究组的T3(2.2±0.5) nmol/L、T4(124.2±17.8) nmol/L、FT3(4.3±0.7) pmol/L及FT4(14.4±2.9) pmol/L与对照组无明显差异(P 0.05),研究组的TSH(1.8±0.2)μIU/L低于对照组(P 0.05);研究组甲状腺抗体水平TG-Ab(253.4±12.8) IU/mL、TPO-Ab(241.3±12.8) IU/mL均低于对照组(P 0.05);研究组IL-8(0.4±0.2) ng/mL、IL-17(7.4±2.1) pg/mL及APN(5.9±1.1)μg/mL低于对照组(P 0.05),研究组的IL-10(91.8±12.6) pg/mL高于对照组(P 0.05);研究组不良反应(22.64%)与对照组(24.53%)无明显差异(P 0.05)。结论:采用小金胶囊联合左甲状腺素钠片治疗桥本氏甲状腺炎患者,能有效改善患者甲状腺抗体水平,调节自身炎症因子平衡,具有较高的安全性,可以在临床中进行进一步推广。     

Genome wide identification of new genes and pathways in patients with both autoimmune thyroiditis and type 1 diabetes

Autoimmune thyroid diseases (AITD) and Type 1 diabetes (T1D) frequently occur in the same individual pointing to a strong shared genetic susceptibility. Indeed, the co-occurrence of T1D and AITD in the same individual is classified as a variant of the autoimmune polyglandular syndrome type 3 (designated APS3v). Our aim was to identify new genes and mechanisms causing the co-occurrence of T1D + AITD (APS3v) in the same individual using a genome-wide approach. For our discovery set we analyzed 346 Caucasian APS3v patients and 727 gender and ethnicity matched healthy controls. Genotyping was performed using the Illumina Human660W-Quad.v1. The replication set included 185 APS3v patients and 340 controls. Association analyses were performed using the PLINK program, and pathway analyses were performed using the MAGENTA software. We identified multiple signals within the HLA region and conditioning studies suggested that a few of them contributed independently to the strong association of the HLA locus with APS3v. Outside the HLA region, variants in GPR103, a gene not suggested by previous studies of APS3v, T1D, or AITD, showed genome-wide significance (p < 5 × 10⁻⁸). In addition, a locus on 1p13 containing the PTPN22 gene showed genome-wide significant associations. Pathway analysis demonstrated that cell cycle, B-cell development, CD40, and CTLA-4 signaling were the major pathways contributing to the pathogenesis of APS3v. These findings suggest that complex mechanisms involving T-cell and B-cell pathways are involved in the strong genetic association between AITD and T1D.     

Therapeutic effect of mesenchymal stem cell on Hashimoto’s thyroiditis in a rat model by modulating Th17/Treg cell balance

Abstract

The autoimmune condition Hashimoto’s thyroiditis (HT) is a disease wherein lymphocytes mediate the autoimmune damage and destruction of the thyroid gland. There are currently no effective means of treating HT, with the primary strategies of thyroid hormone therapy, surgery, or immunomodulatory therapy being associated with serious risks and side effects. There is thus a clear and urgent need to identify novel treatments for HT. In this study, we utilize female SD rats induced HT to evaluated the ability of transplanted MSCs to regulate Th17/Treg interactions in a rat Hashimoto’s thyroiditis (HT) model system. The results showed that Rats in the HT model group exhibited increased thyroid autoantibody levels consistent with successful model development, whereas these levels were lower in rats treated with MSCs. There were also fewer thyroid lesions and less lymphoid infiltration of the thyroid in MSC-treated rats relative to HT model rats, as well as fewer Th17 cells and more Treg cells – an observation consistent with the cytokine analyses. All of these showed that MSCs can regulate Th17/Treg interactions in a rat Hashimoto’s thyroiditis (HT) model system. It suggested that transplanted MSCs could be a potential immunotherapy strategy for the treatment of Hashimoto’s thyroiditis.     

桥本甲状腺炎与甲状腺乳头状癌临床病理特征的相关性分析

目的:探讨桥本甲状腺炎（Hashimoto's thyroiditis,HT）对甲状腺乳头状癌（papillary thyroid carcinoma,PTC）的影响。方法:分析882例经甲状腺切除术且病理证实为PTC患者的临床资料，比较PTC合并HT和非合并HT患者临床病理特征和甲状腺功能，分析HT与PTC临床病理特征的相关性。结果:PTC合并HT组239例（27.10%），非合并HT组643例（72.90%），两组间比较，合并HT组女性、癌灶多发、双侧及淋巴结转移比例显著高于非合并HT组，差异均有统计学意义（均P＜0.05），而年龄、原发灶直径、远处转移、复发危险度分层及TNM分期均无显著性差异（均P＞0.05）。与非合并HT组相比，PTC合并HT组TPOAb、TGAb、TSH水平升高，FT4、FT3水平降低（均P＜0.05）。分别进行Logistic回归分析显示:HT与女性、癌灶多发、淋巴结转移呈独立相关（OR值分别为2.690、1.491、1.514，均P＜0.05）；癌灶多发、原发灶直径>1 cm、合并HT与PTC淋巴结转移独立相关（OR值分别为2.150、2.751、1.465，均P＜0.05）。结论:合并HT的PTC患者女性、多灶及淋巴结转移多见，但不影响预后；癌灶多发、原发灶直径>1 cm、合并HT是PTC淋巴结转移的独立危险因素。