支气管哮喘患者IL-17基因多态性与激素干预疗效的关系

目的:研究支气管哮喘(哮喘)患者白细胞介素17(IL-17)基因多态性与激素干预疗效的关系。方法:本研究为横断面研究。采用随机抽样方法,选取2018年5月至2020年5月三二〇一医院呼吸与危重症医学科收治的84例哮喘患者作为研究对象。患者均接受激素治疗,记录治疗效果。以TaqMan MGB探针技术对IL-17A和IL-...     

Graves甲亢腹泻患者回肠和结肠组织中TSH-β及TSH受体基因的表达

目的探讨Graves甲亢患者腹泻的发病机制。方法应用RT—PCR的方法检测Graves甲亢伴腹泻组（GD组）和结肠易激综合征腹泻型组（IBS—D组）患者回肠与结肠组织中TSH-β和TSH受体（TSHR）基因表达；以免疫组化检测回肠和结肠TSHR阳性细胞。结果两组患者肠组织中均有TSH—β和TSHR基因mRNA表达。甲亢组患者结肠组织中TSH—β基因表达量明显低于IBS—D组（分别为0．137±0．012和0．209±0．015，P〈0．05）；TSHR基因表达量显著高于对照组（分别为0．251±0．017和0．181±0．012，P〈0．05）；而回肠组织中二种基因表达量与对照组无明显差异。两组患者回肠和结肠组织的间质细胞上均有TSHR阳性颗粒沉积，甲亢组患者的回肠组织中TSHR阳性细胞数与对照组无明显差异，而结肠组织间质细胞中TSHR阳性细胞计数明显多于对照组患者（分别为83±8／高倍视野和56±9／高倍视野，P〈0．05）。结论两组患者的回肠和结肠组织中均有TSH—β和TSHR基因的表达，提示Graves甲亢患者的肠道症状可能与TSH—β和TSHR的局部分泌和自身免疫调节有关。     

TSHR胞外区中间段在BALB/c小鼠体内的免疫原性研究

目的观察促甲状腺激素受体（TSHR）胞外区中间段（TSHRm）的免疫调节作用，探讨TSHR分子结构与功能的关系。方法将血蓝蛋白与原核表达的人TS／HRm融合蛋白耦联，间隔15d注入BALB／c小鼠腹腔内共5次，对照组注射生理盐水；检测动物血清T4、促甲状腺激素受体抗体（TRAb）、促甲状腺激素受体刺激抗体（TSAb）、促甲状腺激素受体阻滞抗体（TBAb）水平及甲状腺组织病理变化。结果对照组动物T4水平升高后下降，TRAb水平较实验前升高，TSAb、TBAb无显著变化。实验组动物T4总体水平一直保持升高趋势；免疫30d时血清TRAb水平显著升高（P〈0．001），TSAb、TBAb水平变化表现为先升后降。甲状腺组织的病理变化为甲状腺上皮细胞增生和淋巴细胞浸润。结论 人TSHRm融合蛋白可刺激小鼠产生TRAb、TSAb和TBAb，其对动物机体的影响反映了TSAb和TBAb综合作用的结果，表明TSHRm可能具有TSAb及TBAb两种抗原表位。     

上海市浦东新区周浦和康桥地区孕妇碘营养状况及新生儿足跟血促甲状腺激素水平分析

目的 调查上海市浦东新区周浦和康桥地区(简称周康地区)孕妇的碘营养状况,新生儿足跟血促甲状腺激素(TSH)水平及其与母体孕期尿碘水平之间的关系.方法 于2009年4月至2010年11月,选择上海市周康地区孕早、中、晚期妇女各200例,哺乳期妇女193例,生育期非孕妇女(简称育龄期妇女)200例,同期新生儿200例作为观察对象.采集各期妇女随意1次尿样,用砷铈催化法检测尿碘,同时采集新生儿出生后72 h的足跟血,用时间分辨荧光免疫法(TRFIA)测定TSH.结果 600例孕妇的尿碘中位数为161.35 μg/L,其中孕晚期妇女尿碘中位数(126.35 μg/L)明显低于孕早、中期,哺乳期及育龄期妇女(178.80、180.50、167.90、163.40μg/L,P均＜0.05);孕晚期妇女尿碘＜150 μg/L的比例[57.5％(115/200)]明显高于孕早、中期,哺乳期,育龄期妇女[39.0％(78/200)、39.5％(79/200)、16.6％(32/193)、23.0％(46/200),P均＜0.05].孕早、中、晚期妇女尿碘≥300 μg/L的比例[9.0％(18/200)、8.0％(16/200)、5.0％ (10/200)]明显低于哺乳期、育龄期妇女[20.2％(39/193)、20.5％(41/200),P均＜0.05].200例新生儿足跟血TSH水平为(2.92±1.83)mU/L,范围为0.01～9.76 mU/L,TSH＞5 mU/L的比例为11.0％(22/200),超过世界卫生组织(WHO)碘营养适宜标准(＜3％).结论 上海市浦东新区周康地区孕妇总体碘营养水平处在适宜范围,但孕晚期妇女存在轻度碘营养不足,而该区新生儿有碘营养缺乏的可能.应加强对孕妇碘营养的监测,科学补碘.     

促甲状腺激素受体抗体检测的临床意义

50年前人们发现了促甲状腺激素受体抗体(TRAb),随着对促甲状腺激素受体(TSHR)结构和功能认识的不断更新,加之TSHR信号转导和与TRAb相互作用的逐步阐明,人们对TRAb及其临床应用的认识得到了进一步提高.TRAb的检测在Graves病(GD)及Graves眼病的诊断中有重要作用,并有效预测GD经抗甲状腺药物或放射性碘治疗后复发.其亦可应用于近期服碘的孕妇和乳母,因为甲状腺扫描对她们来说是禁忌的.另外,TRAb有助于胎儿、新生儿甲状腺功能亢进及其他类型的甲状腺毒症的诊断和鉴别诊断.目前,已有文献报道TRAb阳性的GD患者发生甲状腺肿瘤及不良预后之间的可能联系,但尚需更多的前瞻性研究来证实.

Abstract：

It has been 50 years since the discovery of thyrotropin receptor autoantibody (TRAb). Advances in the knowledge of thyrotropin receptor ( TSHR) structure and function, combined with the elucidation of TSHR signaling and TSHR-autoantibody interaction have greatly facilitated our understanding of TRAb and their clinical applications. Measurement of TRAb activity plays an important role in the diagnosis of Graves' disease ( GD) and Graves' opthalmopathy. It has also been well recognized that TRAb is an effective predictor of GD relapse or remission after antithyroid drug and radioactive iodine treatment. TRAb test is of particular help in pregnant women and lactating mothers with recent iodine load, where radioactive iodine or technetium tests are contraindicated. In addition, it is useful in the diagnosis and differential diagnosis of fetal and neonatal hyperthyroidism as well as some rare forms of thyrotoxicosis in clinical practice. Accumulating evidence also indicates the possible correlation between thyroid cancer occurring in GD patients with positive TRAb and adverse outcomes. However, further innovation and standardization of TRAb tests are required to help pave the way for clinical applications.     

重组人生长激素对肝硬化患者肝功能的影响

目的观察重组人生长激素(rhGH)对肝硬化患者血清白蛋白(Albumin)减少,丙氨酸转氨酶(ALT),门冬氨酸转氨酶(AST),胆红素(TBil)异常的治疗效果.方法选择血清白蛋白低于35g/L,肝功能异常的肝硬化病人20例,其中乙型肝炎肝硬化18例,丙型肝炎肝硬化1例,酒精性肝硬化1例.方法rhGH 4～8 IU,皮下注射,1次/d,10d为1个疗程.观察用药前后Alb、ALT、AST、TBil、α-FP、PTA和血糖的变化.结果血清白蛋白由治疗前(28.32士3.86)g/L增加到(30.86±3.91) g/L(P＜0.001);ALT由(59.99±28.97)IU降至(43.90士20.43)IU(P＜0.05),AST由(77.25士34.37)IU降至(59.32士31.08)IU(P＜0.05).其他指标无变化.结论重组人生长激素(rhGH)可以增加肝硬化病人的白蛋白合成,降低ALT、AST水平,改善肝功能,无明显不良反应.     

促肾上腺皮质激素释放因子在炎症性肠病中的研究进展

近年来,越来越多的证据表明应激可干扰神经系统,进而通过脑-肠轴的交互作用引起免疫紊乱,在炎症性肠病(IBD)的发病中起重要作用。促肾上腺皮质激素释放因子(CRF)是一种与应激反应密切相关的神经内分泌肽,其家族成员通过与受体结合,调节机体在应激状态下的下丘脑-垂体-肾上腺(HPA)轴功能,在协调应激相关内分泌、自主神经、免疫、行为等反应中起重要作用。在慢性肠道炎症中,脑和肠黏膜中的CRF系统成员被激活以调节肠道局部和中枢免疫反应。本文对CRF在IBD中作用的研究进展作一综述。     

Hormone sensitivity of gynecological tumor cells in tissue culture

Summary Proliferating tumor cells obtained from ovarian, mammary, and endometrial tumors in tissue culture were tested for the influence of proteohormones and steroid hormones on cellular DNA synthesis and cell growth. The gonadotropic hormones stimulated DNA synthesis of ovarian tumor cells by single administration, or in combination with cortisol, up to the 11-fold of the comparable controls. The hormone sensitivity of the cell lines was variable, resulting in individual reaction patterns. There was no correlation to the histological diagnosis of the primary tumors with respect to the grade of differentiation. The results suggest that ovarian tumor cells in tissue culture can maintain sensitivity to organotropic hormones. Compared to the ovarian carcinoma lines, mammary or endometrial tumor cells did not respond to a similar extent. Progesterone decreased DNA synthesis of endometrial carcinoma cells.     

分化型甲状腺癌患者需要个体化的TSH抑制

分化型甲状腺癌(DTC)流行特征在变化,促甲状腺素(TSH)抑制疗法也在改进.TSH的抑制程度,既要考虑分化型甲状腺癌复发和患者死亡的危险,也应考虑TSH抑制治疗可能带来的危害.不同的分化型甲状腺癌患者需要不同的TSH抑制程度.

Abstract：

The epidemic characteristics of differentiated thyroid cancer(DTC)are changing, thyrotropin(TSH)suppressive therapy is also improving in recent years. The risks of recurrence and the death of patients, as well as the adverse effects of levothyroxine sodium treatment should be fully considered during thyroid hormone administration for patients of DTC. Hence, the degree of TSH suppression should be individualized in patients with DTC.     

从Graves病动物模型看TSHR和TRAb

1996年Shimojo建立了Graves病(GD)动物模型后,开创了用表达促甲状腺激素受体(TSHR)的活体载体接种实验动物的新型GD动物模型。到目前为止,各种动物模型有其各自的优势和劣势,从不同模型中获得的信息远大于单一模型。对动物模型的研究证实,高度糖基化的TSHR的A亚单位启动或是增强了导致甲状腺功能亢进的免疫应答,TSHR氨基端在识别甲状腺刺激性抗体过程中具有重要作用。促甲状腺激素受体抗体(TRAb)的滴度水平和TSAb与TSH阻断性抗体(TBAb)的比例有关,这可能是抗体对免疫显性区的表位限制性所致。     

白细胞介素—1,—6对鼠甲状腺FRTL—5细胞间通讯的影响

为探讨细胞因子对细胞间通讯的影响，应用荧光光淬灭后恢复技术研究白细胞介素（ＩＬ）－１、ＩＬ－６及促甲状腺激素（ＴＳＨ）对鼠甲状腺ＦＲＴＬ－５细胞与细胞间通讯的作用。将培养的ＦＲＴＬ－５细胞加入不同浓度的ＴＳＨ、ＩＬ－１β、ＩＬ－６继续培养１２小时后作荧光染色，以激光扫描仪测定平均荧光恢复速率（ＭＦＲＲ）作为通讯程度的定量指标。结果：（１）用ＴＳＨ后细胞ＭＦＲＲ（单位：％／ｍｉｎ）对照组为０．４４５±０．０３３，０．１、１、５Ｕ／Ｌ组分别为０．６７９±０．０５４、０．９５０±０．０７３、０．７９９±０．０８２（Ｐ＜０．０１）。（２）用ＩＬ－１β后ＭＦＲＲ对照组为０．５６４±０．０３２，１０３、１０４、１０５Ｕ／Ｌ组分别为０．４８５±０．０４２、０．４４５±０．０４３、０．４０５±０．０２９（Ｐ＜０．０１）。（３）ＩＬ－６对ＦＲＴＬ－５细胞胞间通讯无明显影响。提示ＴＳＨ可增强ＦＲＴＬ－５细胞间的通讯，ＩＬ－１β可抑制ＦＲＴＬ－５细胞间的通讯，其作用与ＴＳＨ及ＩＬ－１β的剂量有关。     

17β-雌二醇对人肠系膜动脉的舒张作用及其机制

目的研究17β-雌二醇(E2)对人肠系膜动脉的舒张作用及其机制。方法采用离体血管环灌流的方法,观察E2对内皮完整和去内皮人肠系膜动脉的舒张作用,以及一氧化氮合酶(eNOS)选择性抑制剂N-硝基-L-精氨酸甲酯(L-NAME)、L-NAME+前列环素(PGs)抑制剂吲哚美辛(INDO)、格列本脲(GLY)对这一过程的影响。结果E2(0.5~20.0μmol/L)均可剂量依赖性地舒张人肠系膜动脉;该作用在低水平时内皮完整组明显大于无内皮组(P<0.01),且在内皮完整组E2的舒张作用可分别被L-NAME、L-NAME+INDO、GLY减弱(P均<0.01);高水平时去内皮组与内皮完整组E2的舒张比例差异无统计学意义(P>0.05),在内皮完整组各阻滞剂孵育20 min后E2的舒张作用不能被阻断(P均>0.05)。结论E2对人肠系膜动脉的舒张作用在低水平时具有内皮依赖性,与内皮NO和内皮源性超极化因子(EDHF)的释放、KATP的激活有关,且EDHF比NO更重要;而高水平时的E2舒张人肠系膜动脉是非内皮依赖的,为E2的临床应用提供了重要的实验依据。     

碘过量对大鼠甲状腺细胞线粒体超氧化物生成和膜电位的影响

目的 探讨碘过量对Fisher大鼠甲状腺细胞(FRTL)线粒体超氧化物生成和膜电位(△ψ)的影响.方法 FRTL细胞分别以10-4mol/L碘化钾(KI)、10 U/L促甲状腺素(TSH)、10-4mol/L KI+10 U/L TSH 处理24 h,利用甲基噻唑基四唑(MTT)比色法检测FRTL细胞增殖情况,利用MitoSOX探针通过活细胞影像法检测线粒体超氧化物生成,利用罗丹明123(rh123)通过荧光分光光度计检测△ψ的变化.结果 细胞增殖情况,KI组(0.794±0.144)明显低于对照组(1.000±0.183,P<0.05),TSH组(1.215±0.156)明显高于对照组(P<0.05),KI+TSH组(1.025±0.254)与对照组比较差异无统计学意义(P>0.05),但明显高于KI组(P<0.05);细胞MitoSOX平均荧光强度(MFI),KI组和KI+TSH组(18.16±6.57、13.33±2.92)明显高于对照组(9.74±3.24,P均<0.05),TSH组(6.64±2.15)明显低于对照组(P<0.05),但KI+TSH组明显低于KI组(P<0.05);细胞rh123 MFI,KI组和KI+TSH组(210 593±31 328、295 525±34 243)明显低于对照组(407 824±37 198,P均<0.05),而KI+TSH组明显高于KI组(P<0.05),TSH组(411 187±72 852)与对照组比较差异无统计学意义(P>0.05).结论 碘过量(10-4mol/L KI)能造成FRTL细胞线粒体过氧化损伤,抑制细胞增殖,10 U/L TSH能够促进FRTL细胞增殖,减轻碘过量对FRTL细胞线粒体的过氧化损伤.     

Pituitary-hormone secretion by thyrotropinomas

Hormone secretion by somatotropinomas, corticotropinomas and prolactinomas exhibits increased pulse frequency, basal and pulsatile secretion, accompanied by greater disorderliness. Increased concentrations of growth hormone (GH) or prolactin (PRL) are observed in about 30% of thyrotropinomas leading to acromegaly or disturbed sexual functions beyond thyrotropin (TSH)-induced hyperthyroidism. Regulation of non-TSH pituitary hormones in this context is not well understood. We there therefore evaluated TSH, GH and PRL secretion in 6 patients with up-to-date analytical and mathematical tools by 24-h blood sampling at 10-min intervals in a clinical research laboratory. The profiles were analyzed with a new deconvolution method, approximate entropy, cross-approximate entropy, cross-correlation and cosinor regression. TSH burst frequency and basal and pulsatile secretion were increased in patients compared with controls. TSH secretion patterns in patients were more irregular, but the diurnal rhythm was preserved at a higher mean with a 2.5 h phase delay. Although only one patient had clinical acromegaly, GH secretion and IGF-I levels were increased in two other patients and all three had a significant cross-correlation between the GH and TSH. PRL secretion was increased in one patient, but all patients had a significant cross-correlation with TSH and showed decreased PRL regularity. Cross-ApEn synchrony between TSH and GH did not differ between patients and controls, but TSH and PRL synchrony was reduced in patients. We conclude that TSH secretion by thyrotropinomas shares many characteristics of other pituitary hormone-secreting adenomas. In addition, abnormalities in GH and PRL secretion exist ranging from decreased (joint) regularity to overt hypersecretion, although not always clinically obvious, suggesting tumoral transformation of thyrotrope lineage cells.     

Ghrelin and reproductive disorders

Ghrelin is an important factor involved in most of the metabolic and hormonal signals which adapt the reproductive functions in conditions of altered energy balance. Moreover, the coordinated role of leptin and ghrelin appears in fact to have a specific role in the regulation of puberty. Systemic action of ghrelin on the reproductive axis involves the control of the hypothalamic-pituitary-gondal axis. In addition, it has been shown that ghrelin may directly act at a gonadal level in both females and males. Available data also demonstrate that sex steroid hormones and gonadotropins may in turn regulate the gonadal effect of ghrelin, as documented by studies performed in females with the polycystic ovary syndrome and in hypogonadal men. Notably, recent studies also confirm a potentially important role for ghrelin in fetal and neonatal energy balance, and specifically in allowing fetal adaptation to an adverse intrauterine environment.     

肺结核患者血清IL-17A和IL-17F检测及临床意义

目的研究肺结核（PTB）患者血清IL-17A和IL-17F含量并分析其临床意义。方法ELISA检测47例PTB患者和26名健康志愿者外周血血清IL-17A和IL-17F含量,并分析其相关性。结果PTB患者血清IL-17A含量显著高于健康志愿者。PTB患者和健康志愿者两组之间血清IL-17F含量无显著性差异。常规化疗药物治疗前PTB患者血清IL-17A含量显著高于治疗后。痰涂结核菌反应阳性PTB患者血清IL-17A和IL-17F含量显著高于阴性PTB患者。PTB患者血清IL-17A含量与患者性别、年龄均无关。血清IL-17F含量与患者治疗情况、患者性别及年龄均无明显相关。Pearson相关性分析显示,血清IL-17A和IL-17F含量之间无显著相关性。结论IL-17A和IL-17F均在抗结核免疫过程中发挥重要作用。     

二甲双胍对促甲状腺素影响的初步研究

目的 观察二甲双胍对血清促甲状腺素(TSH)的影响.方法从2型糖尿病患者中,入选原发性甲状腺功能减退症(甲减)患者48例,组1单用二甲双胍而未予左旋甲状腺素(L-T4)替代治疗(n=17),组2给予L-T4稳定替代量的同时加用二甲双胍(n=19),组3用L-T4稳定替代量和非二甲双胍的其他降糖药(n=12).另外20例甲状腺功能正常的其他甲状腺疾病患者(组4)和30例无甲状腺疾病的患者(组5)作为对照.各组患者均定期检测血清TSH、FT3、FT4、TT3、TT4及血糖等主要指标的变化.结果 治疗12个月与基线时比较,组1为(5.05±1.07)对(2.61±0.91)mU/L(P＜0.01),组2为(2.67±1.03)对(1.35±0.74)mU/L(P＜0.01),两组的FT3及FT4均无明显变化.15例TSH显著降低的患者中有13例(87%)在停用二甲双胍后8～12周内TSH由(1.30±0.71)回升至(2.58±1.02)mU/L(P＜0.01).组3、组4及组5的血清TSH和甲状腺激素的水平均无明显改变.结论 服用二甲双胍可使TSH下降.

Abstract：

Objective To evaluate the effects of metformin on thyrotropin(TSH)levels. Methods From the patients with type 2 diabetes mellitus or metabolic syndrome, 48 patients with primary hypothyroidism were enrolled and grouped. 17 patients were treated only with metformin(group A), 19 patients with metformin and stable L-T4substitution(group B), and the remaining 12 patients with antidiabetic drugs(other than metformin)and L-T4(group C). Meanwhile, 20 euthyroid patients with other thyroid abnormalities(group D)and 30 patients without thyroid diseases(group E)served as control. TSH, FT3, FT4, TT3, TT4, and blood glucose were determined regularly in all these subjects. Results After administration of metformin for 12 months, serum TSH were decreased in group A [(5.05±1.07 vs 2.61±0.91)mU/L, P＜0.01] and group B [(2.67±1.03 vs 1.35±0.74)mU/L, P＜0.01]. No difference was found in FT3and FT4in both groups. TSH levels were raised from(1.30±0.71)to(2.58±1.02)mU/L(P＜0.01)within 8～12 weeks in 13 out of 15 patients after metformin withdrawal. Serum TSH and thyroid hormones in the other 3 groups were not significantly changed. Conclusion Administration of metformin may lead to reduction of serum TSH level.     

术前血清促甲状腺素水平与甲状腺结节良恶性关系的研究

]调查了1 870例甲状腺手术患者的术前血清TSH、手术记录、术后组织病理报告等.发现分化型甲状腺癌患者的术前血清TSH明显高于良性甲状腺结节患者[(1.95±1.69对1.40±1.98)mIU/L,P＜0.01].在分化型甲状腺癌患者中,有淋巴结转移或肿瘤直径大于10 mm的患者较无淋巴结转移或肿瘤直径小于10 mm的患者术前血清TSH水平升高(均P＜0.01).提示术前血清TSH水平是预测分化型甲状腺癌风险的一个指标.