BRAFV600E在甲状腺乳头状癌与桥本甲状腺炎相关性中的研究

目的 研究BRAFV600E在甲状腺乳头状癌与桥本甲状腺炎中的表达,探讨甲状腺乳头状癌与桥本甲状腺炎的相关性.方法 北京空军总医院2012年1月-2014年6月经病理证实的甲状腺石蜡标本,甲状腺乳头状癌40例、桥本甲状腺炎20例、甲状腺乳头状癌伴桥本甲状腺炎20例、甲状腺腺瘤20例,采用免疫组化(Envision法)检测BRAFV600E的表达并进行半定量分析,比较其在各组中的表达差异.结果 甲状腺乳头状癌BRAFV600E阳性率为77.5％ (31/40),桥本甲状腺炎BRAFV600E阳性率为45.0％(9/20,P=0.012).甲状腺乳头状癌伴桥本甲状腺炎的肿瘤组织区域BRAFV600E阳性率为70.0％(14/20),与单纯甲状腺乳头状癌的阳性率差异无统计学意义(P=0.156);而桥本甲状腺炎区域BRAFV600E阳性率为55％(11/20,P=0.527),与单纯桥本甲状腺炎BRAFV600E的阳性率差异亦无统计学意义(P＞0.05).甲状腺乳头状癌有转移者BRAFV600E阳性率(88.2％,15/17)高于甲状腺乳头状癌未转移者(69.5％,16/23,P=0.030).甲状腺腺瘤中未检测到BRAFV600E.结论 甲状腺乳头状癌和桥本甲状腺炎均呈现较高的BRAFV600E突变率.     

ELISA测定TMAb和TGAb的临床意义

用ELISA对103例健康人和183例不同甲状腺病患者血清TMAb和TGAb测定,同时检测了血清T_3和T_4值。结果表明,在桥本甲状腺炎、甲状腺机能亢进和原发性甲状腺机能减退患者中,二种抗体的阳性率和阳性程度均显著增高,单纯甲状腺肿和甲状腺腺瘤患者抗体水平正常,亚急性甲状腺炎和甲状腺癌则介于二者之间。桥本甲状腺炎患者TMAb与T_3、T_4间、TGAb与T_4间存在显著的负相关关系。     

桥本甲状腺炎及正常甲状腺组织褪黑素受体亚型基因表达差异的研究

目的　研究成人桥本甲状腺炎及甲状腺腺瘤旁正常甲状腺组织褪黑素受体亚型基因表达的差异及意义。方法　取成人桥本甲状腺炎患者手术切除的甲状腺组织及甲状腺腺瘤瘤旁1. 0cm外正常甲状腺组织,抽提总RNA,合成mt1、MT2 受体引物,用逆转录多聚酶链反应半定量分析褪黑素受体亚型mRNA表达的改变。结果　成人桥本甲状腺炎、甲状腺腺瘤瘤旁正常甲状腺均存在mt1 受体表达,未检测到MT2 受体亚型。桥本甲状腺炎甲状腺组织mt1 受体表达量较正常甲状腺组织明显减少,统计学分析有显著性差异(P<0. 05)。结论　桥本甲状腺炎发病可能与mt1亚型受体抑制有关。褪黑素免疫调节作用可能通过mt1 受体介导。     

甲状腺癌PCDH8基因的转录调控及临床意义

目的研究甲状腺乳头状癌、甲状腺滤泡状腺瘤、结节性甲状腺肿和正常甲状腺组织中原钙黏蛋白8(PCDH8)基因转录调控表达水平,分析PCDH8基因表达与甲状腺乳头状癌患者临床病理特征的关联性。方法选择该院2013～2015年的甲状腺组织标本118例,根据病理结果分为甲状腺乳头状癌组36例、甲状腺滤泡状腺瘤组30例、结节性甲状腺肿组31例和正常甲状腺组织组21例。采用荧光定量PCR法检测各组标本PCDH8基因的表达情况,分析PCDH8基因的表达情况与甲状腺乳头状癌患者临床病理特征的关联性。结果荧光定量PCR的结果显示,正常甲状腺组织组的PCDH8阴性表达率为28. 57%,低于甲状腺乳头状癌组(63. 89%)和甲状腺滤泡状腺瘤组(60. 00%),差异有统计学意义(P 0. 05);但与结节性甲状腺肿组(54. 84%)比较差异无统计学意义(P 0. 05)。PCDH8基因mRNA转录表达情况与肿瘤大小有显著关联(P 0. 05)。结论甲状腺乳头状癌中PCDH8基因表达下调,并与肿瘤大小存在关联,在甲状腺乳头状癌的诊断与治疗中有可能成为一种有潜在价值的生物学肿瘤标志物。     

黏附分子CD44变异剪接体6在甲状腺肿瘤中的表达及其临床意义

目的　探讨CD44变异剪接体 6(CD44V6 )在甲状腺肿瘤组织的表达情况及其与肿瘤发生、发展、浸润和转移的关系。方法　采用免疫组织化学S P法检测 2 0例癌旁甲状腺组织 ,2 4例甲状腺腺瘤和 64例甲状腺癌的石蜡标本CD44V6 表达水平。结果　CD44V6 在甲状腺腺癌的表达率 ( 92 19%)显著高于甲状腺腺瘤者 ( 5 8 3 3 %,P <0 0 1) ,癌旁甲状腺组织未见表达。甲状腺中不同组织来源的滤泡细胞癌和髓样癌的CD44V6 表达差异具有显著性 ,总阳性率分别为 96 5 5 %及 5 0 0 %(P <0 0 1)。但CD44V6 表达水平在乳头状腺癌和滤泡型腺癌间差别无显著性 (P >0 0 5 )。同时发现 2例未分化癌CD44V6 表达均呈强阳性。CD44V6 的表达水平与甲状腺癌的包膜浸润和淋巴结转移有关 ,CD44V6 表达水平在包膜浸润组和未浸润组之间 ,在淋巴结转移组和非转移组之间差别有显著性 (P <0 0 1)。CD44V6 表达与患者年龄、性别、肿瘤的大小无关 (P >0 0 5 )。结论　CD44V6 的表达与甲状腺肿瘤的分化和浸润、转移显著相关 ,检测CD44V6 有助于甲状腺癌的诊断、判断预后并可能为甲状腺癌的手术和术后综合治疗决策提供新的分子生物学指标。     

桥本甲状腺炎和甲状腺癌的关系

近年来,桥本甲状腺炎和甲状腺癌（尤其是乳头状甲状腺癌）患病率均呈上升趋势,桥本甲状腺炎合并甲状腺癌也逐年增加.桥本甲状腺炎与甲状腺癌相关性的机制尚未明了,目前有共同病因学说、癌前病变学说、淋巴细胞浸润学说3种观点,其中共同病因包括辐射、高碘、免疫及促甲状腺激素作用等,在共同病因作用下,桥本甲状腺炎、甲状腺癌患病率均升高.一些分子在桥本甲状腺炎和甲状腺癌高表达,与甲状腺其他疾病存在表达差异,可预测桥本甲状腺炎与甲状腺癌的相关性.甲状腺癌灶周围组织淋巴细胞的浸润也可能与桥本甲状腺炎相关.     

甲状腺疾病时甲状腺组织性激素受体的免疫组织化学研究

目的了解性激素及其受体在甲状腺疾病发病中的作用。方法用免疫组化ＡＢＣ法研究了不同甲状腺疾病时甲状腺组织中的性激素受体（ＡＲ、ＥＲ和ＰＲ）。结果在正常甲状腺组织中有少量的性激素受体表达,但阳性率不高;甲状腺癌组织中性激素受体的表达明显增加,尤其在乳头状腺癌组织中ＡＲ、ＰＲ增加更明显,不仅高于正常人也高于腺瘤和结节性甲状腺肿（Ｐ＜０．０１,０．０１,０．０５）;腺瘤和结节性甲状腺肿的ＥＲ明显高于正常人（Ｐ＜０．０１）;桥本甲状腺炎三种性激素受体的阳性率也高于正常人,但无统计学差异。结论虽然各种甲状腺疾病均多发于女性,但它们与性激素受体的关系不一样,甲状腺癌可能与雄激素及孕激素的作用增强有关,而良性甲状腺疾病与雌激素作用关系更密切     

hNIS基因在不同甲状腺组织中表达的实验研究

目的观察hNIS在不同病理类型的甲状腺组织中的表达情况,进而探讨hNIS表达水平与甲状腺疾病发生、发展的关系。方法收集临床甲状腺术后患者的组织块,包括桥本甲状腺炎3例,甲状腺瘤4例、结节性甲状腺肿4例、Graves病3例、亚急性甲状腺炎2例,分别采应用RT-PCR和Western bolt的方法检测不同病理类型的甲状腺组织中hNISmRNA及蛋白质的表达水平。结果桥本甲状腺炎hNIS表达明显降低,Graves hNIS表达明显增加,亚急性甲状腺炎、结节性甲状腺肿中的hNIS表达低于正常组织,腺瘤中的hNIS表达情况高于正常甲状腺组织。结论不同病理甲状腺组织hNIS在甲状腺疾病中发挥重要的作用,hNIS表达的改变,对甲状腺疾病的发生、发展有着十分重要的意义。     

p14ARF基因变异及其产物表达与甲状腺肿瘤的关系

目的探讨甲状腺肿瘤p14ARF基因变异及其产物的表达与甲状腺肿瘤发生发展的关系.方法应用双重PCR和免疫组化SP法分别检测20例甲状腺腺瘤和28例甲状腺癌组织中p14ARF基因纯合性缺失及其蛋白表达.28例甲状腺癌中,11例甲状腺滤泡癌、12例乳头状癌、4例髓样癌、1例未分化癌.结果①p14ARF基因在甲状腺腺瘤及癌中的纯合性缺失率分别为5.0%、42.9%,二者有显著性差异(P＜0.01). ②p14ARF蛋白在甲状腺腺瘤及癌中的阳性率分别为90.0%、35.7%,二者有显著性差异(P＜0.05).结论①甲状腺肿瘤p14ARF基因纯合性缺失是其蛋白表达失活的重要机制之一,与甲状腺肿瘤的发生发展密切相关.②p14ARF可能是甲状腺肿瘤的分子标志物之一,可作为鉴别甲状腺腺瘤与滤泡癌的辅助指标.     

G蛋白α亚基mRNA在不同甲状腺疾病的表达

目的　观察G蛋白α亚基mRNA在不同甲状腺疾病的表达。方法　收集手术切除的甲状腺组织包括Graves病 5例、结节性甲状腺肿 7例、正常功能甲状腺腺瘤 6例和甲状腺乳头状癌 5例 ,以腺瘤周围组织作为正常甲状腺组织对照 ,观察刺激性G蛋白 (Gs)和抑制性 (Gi)α亚基的表达。结果　 (1 )GsαmRNA的表达 :甲状腺乳头状癌 (1 67± 0 2 5)较正常甲状腺组织 (1 1 0± 0 1 4 )和结节性甲状腺肿 (0 96± 0 31 )明显增高 (P <0 0 5和P <0 0 1 ) ,Graves病 (1 47± 0 1 1 )和正常功能甲状腺腺瘤 (1 36± 0 2 8)均显著高于结节性甲状腺肿 (P <0 0 5) ,但与正常甲状腺组织表达水平相似 ;(2 )Giα 2mRNA的表达 :Graves病显著低于结节性甲状腺肿 (0 68± 0 2 6比 1 1 5± 0 35 ,P <0 0 5) ;(3)Giα 1和Giα 3mRNA在不同甲状腺疾病的表达相似。结论　Gs蛋白α亚基的高表达可能在甲状腺乳头状癌的发病中起重要作用 ,不同疾病时甲状腺G蛋白α亚基具有不同的表达水平     

Three layer functional model and energy exchange concept of aging process

Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of ‘energy flow’ between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called ‘death.’ This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.     

Unusual responses of nocturnal pineal melatonin synthesis and secretion to swimming: Attempts to define mechanisms

Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm²) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Melatonin and photoperiodic time measurement: Seasonal breeding in the sheep

Abstract: Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status—the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.