摘要
目的:探讨结节性甲状腺肿(简称结甲)病因病机及与血瘀、痰凝的关系。观察活血消瘿方治疗结甲的临床疗效,评价其临床应用价值。检测结甲病人外周血中几种相关细胞因子的水平,探讨结甲发病的分子机制。观察活血消瘿方治疗后上述相关细胞因子的变化水平,初步探讨活血消瘿方治疗结甲的作用机制。
方法:本研究分三部分,方法如下:
1.理论研究:分析、整理古籍文献,结合现代临床治疗经验,比较不同医家对结甲的病因、病机的认识以及辨证论治的方法;综合分析现代医学对结甲病因、病理的认识和治疗的经验,寻找研究的突破点。
2.临床疗效研究:采用随机单盲对照法,将符合入选标准的结甲(血瘀痰凝证型)患者90例随机分为2组:试验组(n=45,予以活血消瘿方口服)和对照组(n=45,予以优甲乐片口服),3个月为一个疗程,共2个疗程。观察两组治疗前及治疗后3个月、6个月时的相关指标(包括相关症状及体征、甲状腺的体积及结节的最大直径及结节数目、甲状腺功能等),并作比较分析。
3.临床机理研究:选取本课题第二部分试验组中的完成6个月规范治疗的结甲患者30例作为病例组。同时在门诊体检人群中随机选取30名与之相匹配的健康人作为正常对照组。采用定量酶联免疫吸附试验(ELISA)检测两组治疗前、治疗后3个月及6个月的血清血管内皮生长因子(VEGF).转化生长因子一β1(TGF-β1).可溶性Fas受体(sFas)及可溶性Fas受体配体(sFasL)水平。采用放射免疫分析法(RIA)测定两组治疗前、治疗后3个月及6个月的血清胰岛素样生长因子-Ⅰ(IGF-Ⅰ)、白介素-1β(IL-1β)、白介素-6(IL-6)及肿瘤坏死因子(TNF)的水平。每个指标分别进行病例组治疗前与对照组比较、活血消瘿方治疗前后水平变化的比较。分四个方面进行分析:①活血消瘿方对结甲患者生长因子(VEGF)的影响;②活血消瘿方对结甲患者生长因子(IGF-I.TGF-β1)的影响;③活血消瘿方对结甲患者凋亡因子(sFas、sFasL)的影响;④活血消瘿方对结甲患者免疫调节因子(IL-1β、IL-6及TNF)的影响。从而初步探讨结甲发病的分子机制及活血消瘿方治疗结甲的作用机制。
全部数据均使用SPSS13.0统计软件进行统计学处理。数据以均数±标准差(X±S)表示;组间比较,计量资料用t检验,计数资料用X2检验。
结果:
1.理论研究表明:中医一般将结甲类属于“瘿病”、“瘿瘤”范畴。中医医家普遍认为结甲主要因情志失调、水土失宜、体质因素等引起气机郁结、瘀血阻滞、痰浊凝滞及气、痰、血交阻于颈前而成。对本病结节成因提出气滞、痰凝及血瘀的病机。遣方用药有一定规律性,主要以理气化痰、活血化瘀、软坚散结为主。现代医学对结甲的病因并不完全清楚,般认为其发病机理是由各种原因引起垂体TSH分泌增加,TSH不断刺激甲状腺而使甲状腺反复或持续增生,甲状腺组织长期反复增生与复旧不平衡,纤维组织增生分隔使甲状腺组织形成多发结节。越来越多的研究认为,许多细胞因子可能参与了结甲的发病、病理过程。结甲与细胞凋亡的关系尚不明确。西医对结甲的治疗主要是手术切除和甲状腺激素抑制等药物治疗,但都存在缺陷。因此寻找更安全、有效和方便的结甲治疗药物仍是一个有意义的课题。近十年的研究报道显示,许多中药方剂治疗结甲具有较好的疗效,但大多仅进行临床疗效观察,关于中药治疗机制研究鲜为报道。
2.临床疗效研究显示:2个疗程结束时,可供统计的有效病例:试验组41例,对照组40例。
(1)两组总疗效比较:试验组:总有效率2个疗程为90.2%,1个疗程为73.2%;对照组:总有效率2个疗程为47.5%,1个疗程为37.5%;两组比较均有显著性差异(P<0.05)。显示试验组总有效率高于对照组。
(2)疗程与疗效的关系:两组2个疗程均较1个疗程治疗效果好。
(3)治疗后,两组甲状腺的体积和结节最大直径均较治疗前降低,有显著性差异(P<0.05)。两组间治疗后甲状腺的体积无显著性差异(P>0.05);而结节的最大直径试验组缩小程度大于对照组(P<0.05)。
(4)两组结节大小与疗效关系:2个疗程结束后,统计结果显示,两组有效率:治疗前结节直径小于2cm>2-4cm>4cm以上者。
(5)两组治疗前后甲状腺功能变化:两组游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)及试验组的高灵敏度促甲状腺激素(sTSH)于治疗前及2个疗程治疗后无显著差异(P>0.05);对照组的sTSH沿疗后较治疗前明显降低(P<0.05)。
(6)毒副作用:试验组无明显不良反应。对照组有10例出现不同程度的口干、烦躁、失眠,其中4例出现心悸、发热等症状,其毒副作用发生率为25%。
3.临床机理研究显示:
(1)结甲患者治疗前血清VEGF的水平高于对照组(P<0.05)。经活血消瘿方治疗后,血清VEGF水平在治疗后3个月时有所下降,但较治疗前无显著性差异(P>0.05);治疗后6个月时降至正常水平,与对照组比较无统计学意义(P>0.05)。
(2)结甲患者治疗前血清IGF-I的水平较正常人为高(P<0.05),血清TGF-β1的水平低于正常人(P<0.05)。经活血消瘿方治疗后,血清IGF-Ⅰ水平在治疗后3个月时有所下降,但无统计学意义(P>0.05);在治疗后6个月时比治疗前有明显下降(P<0.05),与对照组比较,无显著性差异(P>0.05)。血清TGF-β1水平在治疗后3个月时明显升高(P<0.01);在治疗后6个月时明显下降,但其仍明显高于治疗前水平(P<0.01),亦高于正常组(P<0.05)。
(3)结甲患者治疗前血清sFas的水平明显高于对照组(P<0.01),血清sFasL的水平低于对照组(P<0.05)。经活血消瘿方治疗后,血清sFas水平在治疗后3个月时有所下降,但无统计学意义(P>0.05);在治疗后6个月时明显下降,较治疗前有极显著性差异(P<0.01),与对照组比较无显著性差异(P>0.05)。血清sFasL;水平在治疗后3个月时明显上升(P<0.05);在治疗后6个月时继续上升,比治疗后3个月及治疗前均有显著性差异(P<0.05),且明显高于正常对照组(P<0.01)。
(4)结甲患者治疗前血清IL-1β及TNF的水平均略高于对照组,但无统计学意义(P>0.05),血清IL-6的水平低于对照组(P<0.05)。经活血消瘿方治疗后,血清IL-1β及TNF水平在治疗后3个月时明显上升(P<0.05);在治疗后6个月时略有下降(P>0.05),且仍高于对照组(P<0.05)。血清IL-6水平在治疗后3个月时有所升高,但与治疗前比较无显著性差异(P>0.05);在治疗后6个月时明显升高达正常范围,比治疗后3个月及治疗前均有显著性差异(P<0.05),与对照组无显著性差异(P>0.05)。
结论:
1.结节性甲状腺肿的病因主要为情志失调、水土失宜;病机为气滞、痰凝、血瘀;中医药治疗结甲取得较好的疗效。
2.活血消瘿方治疗组的总有效率高于优甲乐对照组,且对于结节的缩小乃至消除,活血消瘿方明显优于优甲乐,说明中药活血消瘿方治疗结甲优于优甲乐治疗;两组2个疗程均较1个疗程疗效好;结节的消除与其大小关系密切,结节直径<2cm的疗效好,≥4cm的疗效差;活血消瘿方对于甲状腺分泌激素的功能无明显影响,毒副作用小,安全性能高。
3.生长因子(VEGF、IGF-I、TGF-β1)与结甲的发病、转归关系密切。活血消瘿方可以通过适度下调结甲患者血清VEGF、IGF-I水平及上调血清TGF-β1水平来抑制甲状腺滤泡及组织的增生。
4.凋亡因子(sFas、sFasL)在结甲的发病和治疗中起重要作用,结甲存在细胞凋亡的抑制。活血消瘿方可能通过下调血清sFas水平和上调血清sFasL水平诱导甲状腺细胞凋亡来缩小甲状腺肿及结节,从而达到治疗结甲的目的。
5.免疫调节因子(IL-1β、IL-6及TNF)可能也参与了结甲的发病、转归过程。活血消瘿方可能通过适度升高血清IL-1β、TNF和IL-6水平,诱导甲状腺细胞凋亡,抑制甲状腺滤泡的增生,从而调整甲状腺细胞增生与凋亡的平衡达到治疗目的。
Objective:To explore the Etiology Pathogenesis of nodular goiter (Abbreviation:NG)and the relationship among NG, blood stasis and sputum condensation.To observe the clinical effect of "HuoXueXiaoying" prescription,and to evaluate the clinical value. To detect several cytokines related levels of peripheral blood of patients with NG,and to explore the molecular mechanism of NG'pathogenesis.To observe the related changes in cytokine levels after the treatment of "HuoXueXiaoying" prescription, and to study the mechanism of action in "HuoXueXiaoying" prescription treatment on NG preliminary.
Methods:This study was divided into three parts,as follows.
1.Theoretical studies:Analysis,sorting out ancient literature,combining with modern clinical treatment experience to compare the knowing of NG'etiology,pathogenesis and the dialectical methods of different physicians;comprehensive analyzing NG'etiology, pathogenesis and the treatment experience of modern medicine to find a breakthrough point for this research.
2.Clinical efficacy studies:Used randomized single-blind antithesis,90 NG(blood stasis and sputum condensation type) patients who measure up the standard were divided into 2 groups: experimental group(n=45, to be treated with "HuoXueXiaoying" prescription) and contrast group (n=45,to be treated with euthyrox tablets),3 months for a course of treatment,a total of 2 courses. Then to Observe and analyze comparatively the related indicators (including related symptoms and signs,thyroid nodule size and the maximum diameter and the number of nodules,thyroid function, etc.)before treatment and after treating for 3,6 months.
3. Clinical Mechanism studies:Selected 30 nodular goiter patients who had finished 6 months'standard treatment in the second part of the experimental group in this subject and let them be the case group. At the same time selected 30 matched healthy adults in outpatients randomly as normal control group. Quantitative enzyme-linked immunosorbent assay(ELISA)was used to measure the serum levels of vascular endothelial growth factor (VEGF),transforming growth factorβ1(TGF-β1),soluble Fas(sFas) and soluble Fas Ligand(sFasL)of the two groups before treatment and after treating for 3 or 6 months.Radio immunoassay (RIA) was used to determine the serum levels of insulin-like growth factor I(IGF-I),interleukin 10(IL-10),interleukin 6(IL-6)and tumor necrosis factor(TNF)of the two groups before treatment and after treating for 3 or 6 months.Each indicator should be compared with the control group before the treatment in case group,and then the concentrations changes were compared separately after the treatment of "HuoXueXiaoying" prescription. Sub-analysis of four aspects:①The impact "HuoXueXiaoying" prescription do on vascular endothelial growth factor(VEGF) of the patients with NG;②The impact "HuoXueXiaoying" prescription do on patients with NG' growth factors(IGF-I,TGF-β1);③The impact "HuoXueXiaoying" prescription do on apoptotic factors (sFas、sFasL) of the patients with NG;④The impact "HuoXueXiaoying" prescription do on immune factors (IL-1β,IL-6 and TNF)of the patients with NG. Then explore the molecular mechanism of NG'pathogenesis and the mechanism of "HuoXueXiaoying" prescription treatment on patients with NG preliminary.
All data were analyzed statistically by SPSS13.0 statistical software. Data used mean±standard deviation (X±S) to express; For groups comparison, use t to test measurement data,use X2 to test count data.
Results:
1.Theoretical studies have shown that:Nodular goiter belongs to the category of disease "ying" or "ying gall" of traditional Chinese medicine(TCM)in general.Chinese medicine physicians generally think that NG is mainly due to qi stagnation, blood stasis block,phlegm stagnation and qi,sputum,blood cross-resistance formed on the anterior which caused by emotional imbalance, inappropriate water and soil,physical factors and so on. They put the pathogenesis of qi stagnation, blood stasis and sputum condensation to be the causes of nodules.Medication using should be some regular,that is,mainly regulating qi and phlegm, promoting blood circulation, and resolving hard lump. The cause of NG in modern medicine is not clear entirely.It is generally believed that the reasons of pathogenesis is that pituitary TSH secretion increase because of various factors.
TSH's stimulating thyroid tissues constantly can result in repeating or lasting thyroid hyperplasia.Repeating thyroid hyperplasia and redintegration in a long-term are under imbalance. Thyroid was separated by fibrous tissue to form a multi-nodular thyroid tissue. More and more researches show any growth factors may be involved in the disease and its pathological process.It is unclear whether the pathogenesis of NG is related to thyroid follicular cells apoptosis.Western medicine treatment on NG is mainly surgery and thyroid hormone suppression therapy,etc.But the both are flawed. So looking for more secure,efficient and convenient therapy is still a significant issue. Nearly a decade of research reports indicated that many traditional Chinese medicine prescription treatments on NG have better efficacy, but most of the study is only about clinical efficacy.It is rarely reported on the mechanism of traditional Chinese medicine treatment.
2. Clinical efficacy studies have shown that:When the two courses of the treatment finished, the available statistics was:41 cases of experimental group and 40 patients of contral group.
(1)The total effect of two groups were compared:experimental group:The total effective rate was 87.9% for the two courses,was 73.2% for a course of treatment;control group:The total effective rate was 47.5% for the two courses,was 37.5% for a course of treatment; Two groups compared at different times were different significantly(P<0.05).The experimental group always showed higher efficiency than compared group.
(2)The relationship between treatment time and effect:Both treatment groups which had two courses of treatment had higer efficacy than those in a course of treatment.
(3)After treatment,thyroid volumes and nodule maximum diameters were lower than before.There were significant difference when they were compared in each group separately(P<0.05).Thyriod volumes were not significantly different when they were compared between two groups (P>0.05),and nodules's reduced levels of maximum diameter of the experimental group were more than the control group (P<0.05).
(4)The relationship between nodule size and effect of the two groups:After two courses of treatment,the results showed that the efficiency of two groups depend on pre-treatment nodule diameter:less than 2cm> 2-4cm>more than 4cm.
(5)Changes in thyroid function before and after treatment of the two groups:Free triiodothyronine(FT3),free thyroxine(FT4) of two groups and sensitive thyrotropin(sTSH) in the experimental group before and after two courses of treatment had no significant difference (P>0.05);After treatment the sTSH of the control group was significantly decreased (P<0.05).
(6)Side effects:There was no significantly adverse reaction in the experimental group. In the control group,10 patients had various degrees about dry mouth, irritability, insomnia,and 4 cases in which had palpitations,fever and other symptoms;The rate of its adverse reaction was 25%.
3. Clinical mechanism studies have shown that:
(1)Serum VEGF level of patients with NG in pre-treatment was higher than that of the control group (P<0.05).After "HuoXueXiaoying" prescription treatment,serum VEGF level was reduced 3 months treatment later,but it had no significant difference compared with that before treatment (P>0.05);After 6 months treatment the level was reduced to normal level,compared with the control group, and there was no statistical significance (P>0.05).
(2)Serum IGF-I level of patients with NG in pre-treatment was higher than that of the control group (P<0.05),and serum TGF-β1 level was lower than that of the control group (P<0.05).After "HuoXueXiaoying"prescription treatment,serum IGF-I level was decreased after 3-month treatment,but no statistics significance (P>0.05);After 6 months treatment,it was significantly lower than that before treatment (P<0.05),but there was no significant difference when it was compared with that of the contral group(P >0.05). Serum TGF-β1 level was significantly higher after 3-month treatment(P<0.01));After 6 months treatment,it was decreased obviously,but was still significantly higher than that before treatment (P<0.01),and was also higher than that of the control group (P<0.05).
(3)Serum sFas level of patients with NG in pre-treatment was significantly higher than the control group (P<0.01),and serum sFasL level was lower (P<0.05).After "HuoXueXiaoying" prescription treatment,serum sFas levels was a little decreased after 3-month treatment,but no statistics significance(P>0.05); After 6-month treatment,it was significantly lower than that before treatment (P<0.01),but compared with the control group, it was no sinnificantly different (P>0.05).Serum sFasL level was increased obviousely after 3-month treatment(P<0.05);It increased constantly after 6-month treatment,having significant difference compared with that of patients who had 3-month treatment or were under pre-treatment,and was significantly higher than normal level,compared with the control group (P<0.01).
(4)Serum IL-1βand TNF levels of patients with NG in pre-treatment were a little higher than those of the control group,compared with those before treatment,but there were no significant differences(P>0.05);Serum IL-6 level was lower than that of the control group (P<0.05).After "HuoXueXiaoying" prescription treatment,Serum IL-1βand TNF levels were increased obviousely after 3-month teratment(P<0.05),and were a little decreased after 6-month treatment(P>0.05);And they were higher than normal level,compared with the control group,having statistical significance(P<0.05).Serum IL-6 level has increased after 3-month treatment,but compared with those before treatment,there was no significant difference (P>0.05);It was significantly increased to normal level after 6-month treatment,it was more significantly different than after 3-month treatment and before treatment (P<0.05),and compared with the control group,there was no significant difference (P>0.05).
Conclusion:
1.Nodular goiter mainly dues to qi stagnation, blood stasis block,phlegm stagnation and qi,sputum,blood cross-resistance formed on the anterior neck which caused by emotional imbalance, inappraprite water and soil,physical factors and so on. Chinese medicine treatment on NG has achieved better efficacy.It can avoid patient's cardiac rhythm disorders and osteoporosis and other side effects caused by western medicine, especially is suitable for frail patients.
2.The total effective rate of "HuoXueXiaoying" prescription treated group was higher than that of euthyrox group; "HuoXueXiaoying" prescription is better than euthyrox on reducing or removing the nodules.It's shown that "HuoXueXiaoying" prescription was more clinically effective than euthyrox on treating NG.Both two groups which had 2 courses of treatment were better than those in a course of treatment.It is closely related between the elimination with size of nodules:the efficacy of treatment on nodule diameter<2cm was better, that of>4cm was in poorer treatment outcomes."HuoXueXiaoying" prescription for the function of thyroid hormone secretion had no significant influence, litter toxic side effects,high security and high performance.
3. Growth factors(VEGF, IGF-I,TGF-β1)are closely related to the incidence and prognosis of nodular goiter."HuoXueXiaoying" prescription can suppress the thyroid follicular hyperplasia and thyroid tissue hyperplasia by appropriately reducing serum VEGF, IGF-I levels and increasing serum TGF-β1 level.
4.Apoptotic factors (sFas,sFasL)play an important role in the pathogenes and treatment on nodular goiter.There is suppressed apoptos is in NG. "HuoXueXiaoying" prescription probably can induce apoptosis of thyroid cells to shrink goiter and nodule to achieve the purpose of treating NG through reducing serum sFas level and elevating serum sFasL level.
5.Immune-regulating factors(IL-1 P,IL-6 and TNF)were also probably involved in the pathogenesis and prognosis process of nodular goiter."HuoXueXiaoying" prescription may be through appropriately increasing the serum IL-1β,TNF and IL-6 levels, inducing apoptosis of thyroid cells and inhibiting proliferation of thyroid follicular to adjust the balance between proliferation and apoptosis of thyroid cell for therapeutic purposes.
引文
[1]盖宝东,张学文,崔俊生,等.4453例结节性甲状腺肿临床流行病学调查.中国地方病防治杂志,2003,18(2):118-120.
[2]陈序吾,陈磊.4899例结节性甲状腺肿的临床分析.外科理论与实践,2005,10(6):519-524.
[3]Mackenzie FJ,Mortimer RH. Thyroid nodules and thyroid cancer. Med J Aust,2004,180(5):242-247.
[4]陈序吾,阎朝岐,李福军,等.结节性甲状腺肿2036例临床分析.哈 尔滨医科大学学报,2004,38(5):471-474.
[5]武正炎,沈美萍.结节性甲状腺肿诊治进展.中国普外基础与临床杂志,2004,11(6):483-485.
[6]Gharib H. Changing concepts in the diagnosis and diagnonsis and management of thyroid nodules.Endocrinol metab,Clin Nor Am,1997,26(4):777-800.
[7]Roman SA. Endocrine tumors:evaluation of the thyroid nodule. Curr Opinoncol,2003,15(1);66-70.
[8]Famdon JR.Thyroid surgery from one millennium to the next.Asian J Surg,2001,24(2):79-81.
[9]Pattou F, Combemale F, Fabre S, et al.Hypocalcemia following thyroid surgery:incidence and predietion of outcome. World J Sorg,1998,22(7):718-724.
[10]Rocco Bellantome,Celestino Pio Lombardi,Mauro Boscherini,et al.Predictive factors for recurrence after thyroid lobectomy for unilateral nontoxic goiter in an endemic area:Results of a multivariate analysis.Surgery,2003,136(6):1247-1251.
[11]Zambudio A, Rodriguez J, Riquelme J, et al.Prospective study of post-operative complications after total thyroidectomy for multinodular goiters by surgeons with experience in endocrine surgery. Ann Surg,2004,240(1):18-25.
[12]黄元夕,高峰,毛晓光.结节性甲状腺术后复发的临床分析.黑龙江医学,2006,30(6):470-471.
[13]屠规益.甲状腺肿瘤外科.见:屠规益.现代头颈肿瘤外科学.北京:科学出版社,2004:668-674.
[14]Light GS Jr.Nodular goiter and benign and malignant neoplasms of the thyroid[A].hi:Sabiston DC J.Text book of surgery. 15thed.PhiladelPhia:WB Saunders Company,1997:626.
[15]项鹤彬,赵志军,陈剑峰,等.结节性甲状腺合并甲状腺癌诊治分析.中国肿瘤杂志,2006,15(3):197-198.
[16]Bennedbaek FN,Heged ul.Management of the solitary thyroid nodule:results of a North American survey.J clin Endcrinol Metad,2002,85:2493-2498.
[17]Kukora JS,Sack MJ,Weiss NM. Thyroid nodule [A] In:Cameron JL. Current surgical therapy.7th ed. CV Mosby Inc.2004.
[18]朱晓华,于素芳,茹融融,等.30例女性结节性甲状腺肿的中西医结合治疗.浙江临床医学,2003,5(5):357.
[19]马金鹏.程益春教授治疗甲状腺肿结节肿瘤经验选萃.中医药学刊,2004,22(6):988-989.
[20]蒋红玉,刘安国,陈淑娟.化瘤汤加局部外敷治疗甲状腺良性结节43例疗效察.新中医,2004,36(1):29-31.
[21]劳丹华,康志强.夏枯草膏治疗结节性甲状腺肿疗效观察.广西医学,2005,27(8):1255-1256.
[22]张洪海,吕培文,丁毅.内消连翘丸治疗结节性甲状腺肿的临床观察.北京中医,2006,25(8):453-454.
[23]卢永洪.中药消瘿汤治疗结节性甲状腺肿36例临床分析.中药材,2008,31(8):1296-1297.
[1]张伯臾.中医内科学.上海:上海科学技术出版社,1987,10:18-221.
[2]陈如泉.甲状腺疾病的中西医诊断与治疗.北京:中国医药科技出版社,2001:3-4,42-46,514.
[3]包广勤,黄礼.“甲瘤汤”治疗甲状腺良性肿块123例临床观察.上海中医药杂志,1999,33(2):24.
[4]劳丹华,康志强.夏枯草膏治疗结节性甲状腺肿疗效观察.广西医学杂志,2005,27(8):1255-1256.
[5]朱晓华,于素芳,茹融融等.30例女性结节性甲状腺肿的中西医结合治疗.浙江临床医学杂志,2003,5(5):357.
[6]刘冬岩,王科成,吴永庆.甲1号散治疗145例甲状腺结节.中国中西医结合外科杂志,1996,2(5):354.
[7]简小兵,戴莲仪.甲1方治疗甲状腺良性结节临床观察.中国中医药信息杂志,2004,11(1):72-73.
[8]陈如泉主编.陈如泉教授医论与临床经验选萃.北京:中国医药科技出版社,2007,110-111.
[9]康煌冬,吴信受.中药内外合治结节性甲状腺肿50例分析.实用中医内科杂志,2004,18(3):262.
[10]赵进喜,邓德强,王新歧.甲状腺疾病相关中医病名考辨汇.陕西中医学院学报,2005,26(4):1-3.
[11]卢永洪.中药消瘿汤治疗结节性甲状腺肿36例临床分析.中药材,2008,31(8):1296-1297.
[12]马金鹏.程益春教授治疗甲状腺肿结节肿瘤经验选萃.中医药学刊,2004,22(6):988-989.
[13]张洪海,吕培文,丁毅.内消连翘丸治疗结节性甲状腺肿的临床观察.北京中医,2006,25(8):453-454.
[14]蒋红玉,刘安国,陈淑娟.化瘤汤加局部外敷治疗甲状腺良性结节43例疗效察.新中医,2004,36(1):29-31.
[15]孙以民,支洪波.消瘿膏外敷治疗甲状腺肿.上海中医药杂志,2000,(6):31.
[16]徐建钟,王家骥.金针治疗甲状腺结节30例临床观察.中国针灸,1998,(7):417-418.
[17]胡从富.针刺治疗散发性甲状腺肿35例.浙江中医杂志,2005,(2):85.
[18]尹继全,宋新安.化结散联合左旋甲状腺素治疗良性、多发性甲状腺结节.中国医药指南,2008,6(17):208-209.
[19]姚小红,刘智艳,杜亦旭.耳针配合加碘盐治疗地方性甲状腺肿疗效分析.新疆医科大学学报,2005,28(2):173-174.
[20]曹仰华,崔联民.中药配合针灸治疗地方性甲状腺肿35例.荷泽医专学报,2003,15(3):61.
[21]Knudsen N, Laurberg P, Perrild H, et al.Risk factors for goiter and thyroid nodules.Thyroid,2002,12(10):879-888.
[22]Valentino R,Savastano S,Tommaselli AP, et al.Screening a coastal population in Southern Italy:iodine deficiency and prevalence of goitre,nutritional aspects and cardiovascular risk factors.NutrMetab Cardiovasc Dis,2004,14(1):15-19.
[23]Knudsen N, Bulow I,Laurberg P, et al.Association of tobacco smoking with goiter in a low-iodine-intake area.Arch Intern Med,2002,162(4):439-443.
[24]Volzke H, Schwahn C, Kohlmann T, et al.Risk factors for goiter in a previously.Exp Clin Endocrinol Diabetes,2005,113(9): 507-515.
[25]AnderssonM, Takkouche B, Egli I,et al.Current global iodine status and progress over the last decade towards the elimination of iodine deficiency. Bull World HealthOrgan, 2005,83(7):518-525.
[26]于志恒,陈崇义.世界卫生组织应重视高碘引起甲状腺肿的危害.中国地方病学杂志,2005,24(3):239-241.
[27]董金茹(综述).甲状腺生长及功能的调控因子.天津医科大学学报,2007,13(2):307-310.
[28]Bencomo E,Prez R, Arteaga M F,et al.Apoptosis of cultured granulose-lutein cells is reduced by insulin-like growth factor 1 and may correlate with embryo fragmentation and pregnancy rate.Fertil Steril,2006,85(2):474-480.
[29]Patel VA, Logan A,Watkinson JC. Isolation and characterization of human thyroid endothelial cells.Am J Physiol Endocrinol Metab,2003,284 (1):168.
[30]Vesely D,Astl J,Lastuvka P. Serum levels of IGF-I,HGF, TGFbe-tal,bFGF and VEGF in thyroid gland tumors.PhysiolRes, 2004,53(1):83.
[31]Derwahl M, Studer H. Multinodular goitre:"much more to it than simply iodine ddeficiency".Baillieres Best Pract Res Clin Endocrinol Metab,2000,14(4):577-600.
[32]白耀.甲状腺病学.基础与临床.北京,科学技术文献出版社,2003:333.
[33]Salabe GB. Pathogenesis of thyroid nodules:histological classification?.Biomed Pharmacother,2001,55(1):39-53.
[34]Walter Lawrence Jr,MD, Brian J, et al.Diagnosis and management of patients with thyroid nodules.Journal of Surgical Oncology,2008,80(3):157-170.
[35]Sidoti M,Marino G, Resmini E, et al.The rational use of fine needle aspiration biopsy(FNAB) in diagnosing thyroid nodules,2006,31(2):159-172.
[36]Bonnema SJ,Bennedbaek FN, Ladenson PW, et al.Management of the ontoxic multinodular goiter:a North American survey. Clin Endocrinol Metab,2002,87:112-117.
[37]Hoogendoorn EH, Den Heijer M, Van Dijk AP, et al.Subclinical hyperthyroidism:to treat or not to treat?.Postgrad Med, 2004,80:394-398
[38]陈序吾,陈磊.4899例结节性甲状腺肿的临床分析.外科理论与实践,2005,10(6):519-524.
[39]Colak T,Akca T, Karik A, et al.Totalversus subtotal thyroidectomy for the management of benign multinodular goiter in an endemic region. ANZ J Surg,2004,74(11):974-978.
[40]Lang BH,Lo CY.Total thyroidectomy for multinodular goiter in the elder. AM J Surg,2005,190(3):418-423.
[41]杨连粤,鲁伟群.扩大患侧甲状腺切除术对孤立性甲状腺结节的疗效评价.中国实用外科杂志,2004,24(1):57-58.
[42]杨卫平,邵堂雷,丁家增,等.双侧结节性甲状腺手术切除范围的探讨.中国实用外科杂志,2007,27(5):403-405.
[43]王桐生.结节性甲状腺肿的内镜治疗(附80例报告).中国内镜杂志,2007,13(4):366-368.
[44]Schwartz A. Thyriod surgery:Who should do it? How should it be done?.Thyroid,2005,15(3):185-187.
[45]Hegedus L, Bennedbaek F N. Radioiodine for Non-toxic Diffuse Goiter.Lancet,1997,350(9705):409-410.
[46]Bonnema SJ,Knudsen DU,Bertelsen H,et al.Does radioiodine therapy have an equal effect on substernal and cervical goiter volumes?.Evaluation by magnetic resonance imaging. Thyroid,2002,12:313-317.
[47]Silva MN, Rubio IG, Romao R, et al.Administration of a single dose of recombinant human thyrotrophin enhances the efficacy of radioiodine treatment of large compressive multinodular goitres.Clin Endocrinol,2004,60:300-308.
[48]Medeiros-Neto G,Marui S,Knobel M. An outline concerning the potential use of recombinant human thyrotropin for improving radioiodine therapy of multinodular goiter.Endocrine, 2008,33(2):109-117.
[49]冯晓丽,陈卫,袁林贵.无水乙醇注射治疗甲状腺良性结节40例疗效观察.第三军医大学学报,2004,26(16):1507-1508.
[50]刘晓云.治疗甲状腺结节的新方法-组织间激光消融法.中国实用内科杂志,2007,27(15):1220-1222.
[51]Dossing H, Bennedbaek FN, Hegedus L. Beneficial effect of combined aspiration and interstitial laser therapy in patients with benign cystic thyroid nodules:a pilot study. BrJ Radiol,2006,79(948):943-947.
[52]蒋红玉,吴正治,山林林,等.化瘤膏外敷治疗甲状肿的实验研究.中国中医药科技,2004,11(1):42-43.
[53]张洪海,杨焕杰,丁毅,等.内消连翘丸含药血清人结节性甲状腺细胞分泌及功能的影响.北京医药大学学报,2006,29(7):482-485.
[54]Hammound LJ,Lowdell MW,Cerrano PG, et al.Analysis of apoptosis in relation to tissue destruction associated with Hashimoto's autoimmune thyroiditis.J Pathol,1997,182: 138-144.
[55]Moore D,Ohene-Fianko D,Garcia B,et al. Apoptosis in thyroid neoplasms:relationship with p53 and bcl-2 expression. Histopathology,1998,32:35-42.
[56]赵明,杜宏,王坚,等.非毒性结节性甲状腺肿与细胞凋亡关系的探讨.天津医药,2001,29(9):553-554.
[57]Mezosi E, Yamazaki H, Bretz JD,et al.Aberrant apoptosis in thyroid epithelial cells from goiter nodules.J Clin Endocrinol Metab,2002,87(9):4264-4272.
[58]刘吉成,邱丽萍,金香兰,等.夏莲颗粒剂抗甲状腺肿作用的实验研究.中国药业,2003,12(12):33-34.
[59]Han Y,Zhou J,Yu SJ, et al.Inhibitory effect of Kangjia Pill on thyrocyte proliferation in rat goiter model.Epub,2009, 15(4):284-288.
[60]Laezza C,Mazziotti G,Fiorentino L,et al.HMG-CoA reductase inhibitors inhibit rat propylthiouracil-induced goiter by modulating the ras-MAPK pathway.J Mol Med.2006,84(11): 967-973.
[61]丁选胜,阚毓铭,黄建强.海藻消瘿颗粒对实验性大鼠甲状腺肿的影响.南京中医药大学学报(自然科学版),2000,16(5):282-283.
[62]卢金福,王旭,陈金锭,等.消瘿散结膏对实验性家兔甲状腺肿的影响.南京中医药大学学报,1999,15(5):295-296.
[60]秦贵军,王庆祝,贾贺堂,等.高蛋白质营养抗高碘致甲状腺肿作用 的实验研究.河南医学研究,2000,9(2):103-105.
[64]吴宁,高天舒,李静.黄药子对甲状腺肿大鼠模型影响的实验研究.Chin J Clin Pharmacol,Vol,2008,24 (1):63-67.
[65]张桂华,刘家慧,马春节,等.甲状腺功能低下对大鼠小脑细胞凋亡的影响.中国地方病学杂志,1999,18(4):241-244.
[66]王志兴,陶冬青.陈如泉诊治甲状腺疾病经验.中医杂志,2002,43(8):574-575.
[67]江苏新医学院主编.中药大辞典(下册).上海科学技术出版社,1997,2484-2485.
[68]杨耀芳,杨翊雯,王赛前,等.土鳖虫口服液镇痛、活血化瘀与红细胞免疫研究.中成药,2003,25(6):496-498.
[69]王征,陈晓光,吴岩.土鳖虫溶栓酶抗凝血及抗血栓作用的实验研究.中国实验诊断学,2007,11(9):1143-1145.
[70]邹玺,刘宝瑞.中药土鳖虫体外对胃低分化腺癌细胞BGC-823的抑制作用的研究.时珍国医国药,2006,7:153-156.
[71]毛小平,陈子珺,毛晓健,等.蜈蚣的部分药理研究.云南中医学院学报,1999,22(3):1-7.
[72]司秋菊,王亚利,王鑫国,等.蜈蚣对心肌缺血性损伤小鼠NO及iNOS的影响.山东中医杂志,2004,23(8):492.
[73]司秋菊,王鑫国,白霞,等.蜈蚣对动脉粥样硬化家兔血液流变学的影响.中国老年学杂志,2004,24(9):831.
[74]王亚利,司秋菊,王鑫国,等.蜈蚣对动脉粥样硬化家兔血管平滑肌细胞周期c-myc基因表达的影响.中药药理与临床,2001,17(6):28.
[1]吴阶平,裘法祖.黄家驷外科学.第6版.北京:人民卫生出版社,2000:811-812.
[2]白耀.甲状腺病学.第2版.北京:科学技术文献出版社,2003:326-330.
[3]蔡永敏,曹金梅,徐学功,主编.现代中医药临床内分泌病学.北京:中国中医药出版社,2001:204-210.
[4]陈如泉主编.陈如泉教授医论与临床经验选萃.北京:中国医药科技出版社,2007.110-111.
[5]Walter Lawrence Jr, Brian J, Kaplan MD. Diagnosis and management of patients with thyroid nodules.Journal of Surgical Oncology,2008,80(3):157-170.
[6]Sidoti M,Marino G, Resmini E, et al.The rational use of fine needle aspiration biopsy(FNAB) in diagnosing thyroid nodules,2006,31(2):159-172.
[7]中华人民共和国卫生部.中药新药临床研究指导原则.北京:中国中医药科技出版社,2002:228-229.
[8]Quadbeck B,Pruellage J,Roggenbuck U, et al.Long-term follow-up of thyroid nodule growth.Exp Clin Endocrinol Diabetes,2002,110(7):348-354.
[9]Zambudio A, Rodriguez J, Riquelme J,et al.Prospective study of post-operative complications after total thyroideetomy for multinodul argoiters by surgeons with experience in endocrine surgery. Ann Surg,2004,240(1):18-25.
[10]黄元夕,高峰,毛晓光.结节性甲状腺术后复发的临床分析.黑龙江医学,2006,30(6):470-471.
[11]Bennedbaek FN,Heged ul.Management of the solitary thyroid nodule:results of a North American survey. J clin Endcrinol Metad,2002,85:2493-2498.
[12]Kukora JS,Sack MJ,Weiss NM. Thyriod nodule [A] In:Cameron JI.Current surgical therapy.7th ed.CV Mosby Inc.2004.
[13]陈序吾,陈磊.4899例结节性甲状腺肿的临床分析.外科理论与实践,2005,10(6):519-524.
[14]劳丹华,康志强.夏枯草膏治疗结节性甲状腺肿疗效观察.广西医学,2005,27(8):1255-1256.
[15]张洪海,吕培文,丁毅.内消连翘丸治疗结节性甲状腺肿的临床观察.北京中医,2006,25(8):453-454.
[16]卢永洪.中药消瘿汤治疗结节性甲状腺肿36例临床分析.中药材,2008,31(8):1296-1297.
[1]钟霞,赵家军,高聆,等.VEGF. bFGF与Graves病甲状腺组织血管形成的相关性研究.山东大学学报(医学版),2005,43(12):1116-1119.
[2]Leung DW, Cachianes K, Kuang WJ, et al.Vascular permeability factor,an endothelial cell mitogen related to PDGF. Science,1989,246:1306-1309.
[3]Collins P. Characterization of the inerease in vascular permeability induced by vascular permeability factor in vivo.Br J Pharmaeol,1993,109:360-368.
[4]Donovan D, harmey J,Toomey D, et al.TGF beta-1 regulation of VEGF Producton by breast cancer cells.Ann-Surg-oneol,1997, 4 (8):621-627.
[5]Cheng WF, Chen CA, Lee CN, et al.Vaseular epithelial growth factor incervical carcinoma.Gynecol,1999,93:761-765.
[6]Atan M, Gregory Y, David B, et al.Plasma levels of vascular endothelial growth factor(VEGF)and its receptor,Fit-1, in haematological cancers:a comparison with breast cancer. Am J Hema,2001,66:59-61.
[7]Jaequeline A,Panline J,Sarah D, et al.Vaseular endothelial growth factor in breast cancer:comparison of plasma,serum and tissue VEGF and microvessel density and effects of Tamoxifen. Cancer Ras,2000,60:2898-2905.
[8]Lissoni P, Fugamalli E,Malugani F, et al.Chemotherapy and angiogenesis in advanced cancer:vaseular end othelial growth faetor(VEGF) decline as predietor of disease control during taxoltherapy in metastatie breast cancer.IntJ Biol Markers,2000,15(4):308-311.
[9]钟霞,赵家军,戴晓华,等.VEGF.IGF-I与Graves病患者甲状腺内血管形成的关系.中华内分泌代谢杂志,2006,22(2):119-120.
[10]Sato K, Yamazaki K, Shizume K, et al.Stimulation by thyroid-stimulating hormone and Grave's immunoglobuling of vascular endothelial growth factor mRNA expression in human thyroid follicles in vitro and flt mRNA expression in the rat thyroid in vivo. J Clin Invest,1995,96(3):1295-1302.
[11]Tang K, Breen EC, Wagner H, et al.HIF and VEGF relationships in response to hypoxia and sciatic nerve stimulation in rat gastrocnemius.Respir Physiol Neurobiol,2004,144(1):71-80.
[12]Hong KH,Ryu J,Han KH. Monocyte chemoattractant protein-1-induced angiogenesis is mediated by vascular endothelial growth factor-A.Blood,2005,105(4):1405-1407.
[13]Zhu BQ, Heeschen C, Sievers RE, et al.Second hand smoke stimulates tumor angiogenesis and growth. Cancer Cell,2003, 4:191-196.
[14]Tuttle RM, Fleisher M, Francis GL, et al.Serum vascular endothelial growth factor levels are elevated in metastatic differentiated thyroid cancer but not increased by short-term TSH stimulation. Journal of Clinical Endocrinology and Metabolism,2002,87:1737-1742.
[15]Sorvillo F,Mazziotti G, Carbone A, et al.Recombinant human thyrotropin reduces serum vascular endothelial growth factor levels in patients monitored for thyroid carcinoma even in the absence of thyroid tissue. Journal of Clinical Endocrinology and Metabolism,2003,88:4818-4822.
[16]Kilicarslan AB, Ogus M, Arici C, et al.Clinical importance of vascular endothelial growth factor (VEGF) for papillary thyroid carcinomas.Acta Pathologica,Microbiologica et Immunologica Scandinava,2003,111:439-443.
[17]Lennard CM, Patel A, Wilson J,et al.Intensity of vascular endothelial growth factor expression is assiociated with increased risk of recurrence and decreased disease-free survival in papillary thyroid cancer. Surgery,2001,129: 552-558.
[18]Klein M, Vignaud JM, Hennequin V, et al.Increased expression of the vascular endothelial growth factor is a pejorative prognosis marker in papillary thyroid carcinoma. Journal of Clinical Endocrinology and Metabolism,2001,86:656-658.
[19]Fenton C, Patel A, Dinauer C, et al.The expression of the vascular endothelial growth factor and the type 1 vascular endothelial growth factor receptor correlate with the size of papillary thyroid cancer in children and young adults. Thyroid,2000,10:349-357.
[20]Lewy-Trenda I,Wierzchniewska-Lawska A. Expression of vascular endothelial growth factor (VEGF) in thyroid tumors. Polish Journal of Pathology,2002,53:129-132.
[21]Siironen P, Louhimo J, Nordling S, et al.Prognostic factors in papillary thyroid cancer:an evaluation of 601 consecutive patients.Tumour Biology,2005,26:57-64.
[22]Klubo-Gwiezdzinska J,Junik R,Kopczynska E, et al.The compareson of serum vascular endothelial growth factor levels between patients with metastatic thyroid cancer,and patients with nontoxic multinodular goiter.Eur J Endocrinol, 2007,157(4):521-527.
[23]Sorisky A, Bell A & Gagnon A.TSH receptor in adipose cells. Hormone and Metabolic Research,2000,32:468-474.
[1]Rotman-Pikielny P,Brucker-Davis F,TurnerML, et al.Lack of effect of long-term octreotide therapy in severe thyroid-associated dermopathy.Thyroid,2003,13(5):465-470.
[2]TMitsiades CS, Poulaki V,Mitsiades N, et al.Endocrine evaluation of patients with critical illness.Endocrinol Metab Clin North Am,2003,32(2):385-410.
[3]Van den Berghe G.Endocrine evaluation of patients with critical illness.Endocrinol Metab Clin North Am,2003,32(2): 385-410.
[4]Gartner R. Growth factors in thyroid cells.CurrTop Pathol, 1997,91:65.
[5]Clement S, Refetoff S, Robaye B. Low TSH requirement and goiter in transgenic mice overexpressing IGF-I and IGF-Ir receptor in the thyroid gland.Endocrinology,2001,142(12):5131.
[6]Kimura T, Van Keymeulen A, Golstein J, et al.Regulation of thyroid cell proliferation by TSH and other factors:a critical evaluation of in vitro models.EndocrRev,2001,22(5):631-656.
[7]Mitsiades CS, PoulakiV,Mitsiades N. The role of apoptosis inducing receptors of the tumor necrosis factor family in thyroid cancer.J Endocrinol,2003,178(2):205-216.
[8]T Mitsiades CS,Poulaki V,Mitsiades N. The role of apoptosis-inducing receptors of the tumor necrosis factor family in thyroid cancer.J Endocrinol,2003,178(2):205-216.
[9]钟霞,赵家军,高聆,等.胰岛素样生长因子-I与Graves病患者甲状腺体积关系的研究.山东大学学报(医学版),2006,44(2):138--142.
[10]Brzozowska M,Kinalska I,Kretowski A. The level of IGF-1 and TGF-beta-1 in the blood serum and the thyroid size in children with normal ioduria.Endokrynol Diabetol Chor Przemiany M ateriiW iekuRozw,2005,11(4):215-220.
[11]Kenchappa P, Yadav A, Singh G, et al.Rescue of TNFa-inhibited neuronal cells by IGF-1 involves Akt and c-Jun N-terminal kinases.Neurosci Res,2004,76(4):466-474.
[12]Bencomo E, Prez R, Arteaga M F, et al.Apoptosis of cultured granulose-lutein cells is reduced by insulin-like growth factor 1 and may correlate with embryo fragmentation and pregnancy rate.Fertil Steril,2006,85(2):474-480.
[13]薛亚梅,李坤,吕杰强.IGF-1对细胞凋亡的抑制调控.生命科学,2007,19(1):68-72.
[14]Drugarin D, Negru S, Koreck A, et al.The pattern of a T(H) lcytokine in autoimmune thyroiditis.Immunol Lett,2000, 71(2):73-77.
[15]Carneiro C,Alvarez CV,Zalvide J,et al.TGF-01 action on FRTL-5 cells provide a model for the physiological regulation of thyroid growth.Oncogene,1998,16:1455-1465.
[16]Phillips IE,Becks GP, Logan A, et al.Altered expression of insulin-like growth factor-I (IGF-1)and IGF binding proteins during rat thyroid hyperplasia and involution. Growth actors,1994,10:207-222.
[17]Logan A, Snith C, Becks GP, et al.Enhanced expression of transforming growth factor-β1 during thyroid hyperplasia in rats.J Endocrinol,1994,141:45-57.
[18]Asmis LM,Kaempf J,Von Gruenigen C. Acquired and naturaly occurring iesistance of thyroid follicular cells to the growth inhibitory action of transforming growth factor-β1(TGF-β1).J En-docrinol,1996,149(3):485.
[19]Eszlinger M, Krohn K, Kratzsch J, et al.Growth factor expression in cold and hot thyroid nodules.Thyroid,2001,11(2):125-135.
[20]Yu S,Fang v, Sharp GC, et al.Transgenic Expression of TGF-{beta} on Thyrocytes Inhibits Development of Spontaneous Autoimmune Thyroiditis and Increases Regulatory T Cells in Thyroids of NOD.H-2h4 Mice.JImmunol,2010 Mar 24.
[21]Cerutti JM, Ebina KN, Matsuo SE, et al.Expression of Smad4 and Smad7 in human thyroid follicular carcinoma cell lines. Journal of Endocrinological Investigation.2003,26:516-521.
[22]Matsuo SE, Ebina KN, Kulcsar MA, et al.Activin betaB expression in rat experimental goiter and human thyroid tumors. Thyroid,2003,13:239-247.
[1]Hammound LJ,Lowdell MW,Cerrano PG,et al.Analysis of apoptosis in relation to tissue destruction associated with Hashimoto's autoimmune thyroiditis.J Pathol,1997,182:138-144.
[2]Moore D, Ohene-Fianko D, Garcia B, et al.Apoptosis in thyroid neoplasms:relationship with p53 and bcl-2 expression. Histopathology,1998,32:35-42.
[3]赵明,杜宏,王坚,等.非毒性结节性甲状腺肿与细胞凋亡关系的探讨.天津医药,2001,29(9):553-554.
[4]Mezosi E, Yamazaki H, Bretz JD,et,al.Aberrant apoptosis in thyroid epithelial cells from goiter nodules.J Clin Endocrinol Metab,2002,87(9):4264-4272.
[5]Kerr J F, Wyllie A H, Currie A R. Apoptosis:a basis biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer,1972,26 (4):239-257.
[6]张晓军,姚天明,王文亮.细胞凋亡的最新研究进展.第四军医大学学报,2002,23:42-44.
[7]Vermeulen K, Van Bockstaele DR,Berneman ZN.Apoptosis: mechanisms and relevance in cancer. Ann Hematol,2005,84 (10):627-639.
[8]Vaux DL. Apop tosis timeline. CellDeath Differ,2002,9:349-354
[9]Itoh N, Yonehara S, Ishii A, et al.The polypeptide encoded by the cDNA for human cell surfaceantigen Fas can mediate apoptosis.Cell 1991,66(2):233-243.
[10]Nagata S, Golstein P. The Fas death factor. Science,1995, 267(5203):1449-1456.
[11]Hara H,Morita Y, Sato R, et al.Circulating nuclear matrix protein in Graves'disease.Endocr J,2002,49:343-347.
[12]anaka M, Suda T,Yatomi T,et al.J Immunol,1997,158(5):2303.
[13]谢克俭,张琦,潘芙蓉,等.可溶性细胞凋亡蛋白Fas在自身免疫性甲状腺疾病患者循环血中的表达.温州医学院学报,2007,3(1):36-38.
[14]Wu X, Liu C, Duan Y, et al.Gene expression of Fas,soluble Fas and Fas ligand in thyroid tissues and thyrocytes from patients with Graves disease. Endocrine J,2000,47 (suppl): 120-125.
[15]武晓泓,刘超,刘翠萍,等.Graves病患者甲状腺细胞凋亡的初步研究.中华内分泌代谢杂志,2002,18(1):33-35.
[16]Mysliwiec J,Okota M, Nikolajuk A, et al.Soluble Fas,Fas ligand and Bcl-2 in autoimmune thyroid diseases:relation to humoral immune response markers.Adv Med Sci,2006,51:119-122.
[17]Fountoulakis S, Vartholomatos G, Kolaitis N, et al. Differential expression of Fas system apoptotic molecules in peripheral lymphocytes from patients with Graves'disease and Hashimoto's thyroiditis.Eur J Endocrinol.2008,158(6): 853-859.
[18]Wang CY,Zhong WB, Chang TC, et al.Circulating soluble Fas ligand correlates with disease activity in Graves' hyperthyroidism. Metabolism,2002,51(6):769-773.
[19]Kolomecki K,Maciaszczyk P,Stepien H,et al.P53 concentration and soluble FasL (sFasL) serum level as indicators of apoptosis in patients with benign and malignant thyroid tumors.Bratisl Lek Listy,2005,106(10):297-300.
[20]Mysliwiec J,Oklota M, Nikolajuk A, et al.Age related changes of soluble Fas,Fas ligand and Bcl-2 in autoimmune thyroid diseases.Endokrynol Pol,2007,58 (6):492-495.
[1]赵明,杜宏,王坚,等.非毒性结节性甲状腺肿与细胞凋亡关系的探讨.天津医药,2001,29(9):553-554.
[2]Giordano C, Stassi G, DeMaria R, et al.Potential involvement of Fas and its ligand in the pathogenesis of Hashimoto's thyroiditis.Science,1997,275:960-963.
[3]Kawakami A, Eguchi K, Matsuoka N, et al.Thyroid-stimulating hormone inhibits Fas antigen mediatedap optosis of human thyrocytes in vitro.Endocrinology,1996,137:3163-3169.
[4]MacEwan DJ.TNF receptor subtype signalling:differences and cellular consequences.Cell Signal,2002,14:477-492.
[5]武晓泓,刘超,覃又文,等.细胞因子白介素-1、白介素-6及肿瘤坏死因子-α对甲状腺细胞凋亡的调节.中华医学会第六次全国内分泌学会论文汇编·大会发言,2001.39.
[6]蔡东升,刘超(综述).细胞因子与甲状腺.《国外医学》内分泌学分册,1997,17(1):7-10.
[7]Giordano C, Stassi G, De Maria R, et al.Potential involvement of Fas and its ligand in the pathogenesis of Hashimoto's thyroiditis.Sciences,1997,275:960-963.
[1]Gharib H. Changing concepts in the diagnosis and diagnonsis and management of thyroid nodules.Endocrinol metab, Clin Nor Am,1997,26(4):777-800.
[2]张伯臾.中医内科学.上海:上海科学技术出版社,1987,10:218-221.
[3]陈如泉.甲状腺疾病的中西医诊断与治疗.北京:中国医药科技出 版社,2001:3-4,42-46,514.
[4]王志兴,陶冬青.陈如泉诊治甲状腺疾病经验.中医杂志,2002,43(8):574-575.
[5]宋立人,洪询,丁绪亮,等.现代中药学大辞典(下册).人民卫生出版社,2001,2268-2269.
[6]李浩明.蜣螂的临床应用,中医外治杂志,2000,(3):9.
[7]江苏新医学院主编.中药大辞典(下册).上海科学技术出版社,1997,2484-2485.
[8]杨耀芳,杨翊雯,王赛前,等.土鳖虫口服液镇痛、活血化瘀与红细胞免疫研究.中成药,2003,25(6):496-498.
[9]贺卫和,成细华,徐爱良.土鳖虫提取液对家兔抗凝血作用的实验研究.湖南中医学院学报,2003,23(2):7-9.
[10]王怡,翁维良,刘剑刚.动物类活血化瘀药对血液流变性作用的比较研究.中药药理与临床,1997,13(3):1-4.
[11]于燕,刘继兰,王菊英,等.土鳖虫水提液对实验性高脂血症大鼠血管内皮细胞的保护作用.山东大学学报:医学版,2002,40(5):398-400.
[12]于燕,刘继兰,王菊英,等.土鳖虫水提物对实验性高脂血症大鼠血管内皮和内皮素的影响.中国生化药物杂志,2003,24(1):15-17.
[13]王征,陈晓光,吴岩.土鳖虫溶栓酶抗凝血及抗血栓作用的实验研究.中国实验诊断学,2007,11(9):1143-1145.
[14]邹玺,刘宝瑞.中药土鳖虫体外对胃低分化腺癌细胞BGC-823的抑制作用的研究.时珍国医国药,2006,7:153-156.
[15]张微,邹玺,钱晓萍,等.土鳖虫含药血清对肝癌HepG-2细胞增殖的抑制作用.中药新药与临床药理,2007,18(4):257-259.
[16]刘自力.救世良方文献研究.昆明:云南民族出版社,2007:154.
[17]毛小平,陈子珺,毛晓健,等.蜈蚣的部分药理研究.云南中医学院学报,1999,22(3):1-7.
[18]司秋菊,王亚利,王鑫国,等.蜈蚣对心肌缺血性损伤小鼠NO及iNOS的影响.山东中医杂志,2004,23(8):492.
[19]司秋菊,王鑫国,白霞,等.蜈蚣对动脉粥样硬化家兔血液流变学的影响.中国老年学杂志,2004,24(9):831.
[20]王亚利,司秋菊,王鑫国,等.蜈蚣对动脉粥样硬化家兔血管平滑肌细胞周期c-myc基因表达的影响.中药药理与临床,2001,17(6):28
[21]韩旭.汪履秋论治痹证初析.湖北中医杂志,1998,20(5):10.
[22]中华本草编委会.中华本草,第3册.上海:上海科学技术出版社,1999,544.
[23]国家药典委员会.中国药典(一部).北京:化学工业出版社,2005,233.
[24]王爱武,王梅,袁久荣,等.猫爪草提取物体外抗肿瘤作用的研究.天然产物研究与开发,2004,16(6):259.
[25]周立,张炜,许津.猫爪草有效成分诱生肿瘤坏死因子的作用.中国医学科学院学报,1995,17(6):456.
[26]费世杰,陈涛.中药抗排斥反应的研究进展.中华实用中西医杂志,2003,3(16):984-986.
[27]Klubo-Gwiezdzinska J,Junik R, Kopczynska E, et al.The compareson of serum vascular endothelial growth factor levels between patients with metastatic thyroid cancer,and patients with nontoxic multinodular goiter.Eur J Endocrinol. 2007,157(4):521-527.
[28]朱祥胜(综述),李国杰(审校).甲状腺结节性病变的超声诊断进展.Medical Recapitulate,2008,14(19):3016-3018.
[29]陈文,张武,苗立英,等.甲状腺恶性肿瘤的二维及彩色多普勒超声征象及其临床意义.中国超声医学杂志,2000,16(7):495-496.
[30]Sato K, Yamazaki K, Shizume K, et al.Stimulation bythyroid-stimulating hormone and Grave's immunoglobuling of vascular endothelial growth factor mRNA expression in human thyroid follicles in vitro and flt mRNA expression in the rat thyroid in vivo. JClin Invest,1995,96(3):1295-1302.
[31]Tang K,Breen EC, Wagner H, et al.HIF and VEGF relationships in response to hypoxia and sciatic nerve stimulation in rat gastrocnemius.Respir Physiol Neurobiol,2004,144(1):71-80.
[32]Hong KH, Ryu J,Han KH.Monocyte chemoattractant protein-1-induced angiogenesis is mediated by vascular endothelial growth factor-A. Blood,2005,105(4):1405-1407.
[33]Brzozowska M,Kinalska I,Kretowski A. The level of IGF-1 and TGF-beta-1 in the blood serum and the thyroid size in children with normal ioduria.Endokrynol Diabetol Chor Przemiany M ateriiW iekuRozw,2005,11(4):215-220.
[34]Kimura T, Van Keymeulen A,Golstein J,et al.Regulation of thyroid cell proliferation by TSH and other factors:a critical evaluation of in vitro models.EndocrRev,2001,22 (5):631-656.
[35]Mitsiades CS,PoulakiV,Mitsiades N. The role of apoptosis-inducing receptors of the tumor necrosis factor family in thyroid cancer.J Endocrinol,2003,178(2):205-216.
[36]T Mitsiades CS, Poulaki V,Mitsiades N. The role of apoptosis-inducing receptors of the tumor necrosis factor family in thyroid cancer.J Endocrinol,2003,178(2):205-216.
[37]Hoelting T,Zieke A, Siperstein AE,et al.Transforming growth factor betal is a negative regulator or differentiated thyroid cancer:studies of growth, migration, invasion, and adhesion of cultured follicular and popillary thyroid cancer cellline. J Clin Endocrinol Metab,1994,79(3):806.
[38]Suzuki J, Otsuka F, Takeda M, et al.Functional roles of the bone morphogenetic protein system in thyrotrop in signaling in porcine thyroid cells.Biochem Biophys Res Commun,2005, 327(4):1124-1130.
[39]NicolussiA,D'Inzeo S,Santulli M,et al.TGF-beta control of rat thyroid follicular cells differentiation.Mol Cell Endocrinol,2003,207(1-2):1-11.
[40]Nagata S, Golstein P. The Fas death factor. Science,1995,267 (5203):1449-1456.
[41]Hara H, Morita Y, Sato R, et al.Circulating nuclear matrix protein in Graves'disease.Endocr J,2002,49:343-347.
[42]Mezosi E, Yamazaki H, Bretz JD,et al.Aberrant apoptosis in thyroid epithelial cells from goiter nodules.J Clin Endocrinol Metab,2002,87(9):4264-4272.
[43]Hammound LJ,Lowdell MW,Cerrano PG,et al.Analysis of apoptosis in relation to tissue destruction associated with Hashimoto's autoimmune thyroiditis.J Pathol,1997,182: 138-144.
[44]Moore D, Ohene-Fianko D, Garcia B, et al.Apoptosis in thyroid neoplasms:relationship with p53 and bcl-2 expression. Histopathology,1998,32:35-42.
[45]赵明,杜宏,王坚,等.非毒性结节性甲状腺肿与细胞凋亡关系的探讨.天津医药,2001,29(9):553-554.
[46]刘超.白介素-6与甲状腺.国外医学·内分泌学分册,1999,19(3):117.
[47]蔡东升,刘超,蒋须勤,等.肿瘤坏死因子-α对Graves病患者甲状腺细胞基因表达的影响.中华内分泌代谢杂志,1999,15(1):31.
[48]Jones.Interleukin-6 an endocrine cytokine.Clin Endocrinol, 1994,40:703.
[49]Pekary AE, Berg L, Wang J, et al.TNF-α,TSH and aging regulate TGF-beta synthesis and secretion in FRTL-5 rat thyroid cells. Am J Physiol,1995,268 (3/2):808.
[50]段宇,刘超.粘附分子与自身免疫性甲状腺疾病.国外医学·内分泌学分册,1998,18(增):8.
[51]Geenen.V.The thymic isulin-like growth factor axis: involvementin Physiology and disease. Horm Metab Res.2003, 35(1-112):63-656.
[52]Even V,Brilot F. Role of thet thymus in the development of tolerance and autoimmunity towards the neuroendoerine systcm.Ann N YAcad Sei,2003,992:95-186.
[53]Savino W,Postel-Vinay MC,Smaniotto S,et al.The thymus gland:a target organ for growth hormone.JImmunol,2002, 55(5):52-442.
[54]MacEwan DJ.TNF receptor subtype signalling:differences and cellular consequences.Cell Signal,2002,14:477-492.
[55]武晓泓,刘超,覃又文,等.细胞因子白介素-1、白介素-6及肿瘤坏死因子-α对甲状腺细胞凋亡的调节.中华医学会第六次全国内分泌学会论文汇编·大会发言,2001,39.