IL—17与支气管哮喘

白介素－17（IL－17）是由活化CD4^ 、CD45RO^ 记忆T细胞产生的一种细胞因子。IL－17在体外能激活支气管哮喘（哮喘）患者的成纤维细胞（FB）、巨噬细胞产生并分泌一系列与气道重构有关的细胞因子，如GM－CSF、TNF－α、IL－1β等，还能与FB一起支持CD34^ 造血前体细胞增殖和分化成熟为中性粒细胞，是T细胞诱导的炎症反应的早期启动因素，可能参与哮喘的发病与气道重构。本文综述了近年来这方面的进展。     

IL-5、Eotaxin与支气管哮喘

IL-5是由CD4^ T细胞TH2亚型产生的一种糖蛋白,哮喘时明显增多，能促进骨髓池中的嗜酸粒细胞(EOS)分化、成熟、增殖并进入血循环，通过上调sICAM-1而使EOS趋化、黏附、渗出到气道组织,为EOS浸润提供充足的细胞来源．是EOS趋化和募集的必要因素，还可促使其活化释放各种毒性蛋白,参与过敏性哮喘过程并使气道反应性明显增高，还能抑制EOS的凋亡而延长其存活时间。Eotaxin是cc趋化因子家族成员之一。由结构性细胞和渗出性炎症细胞产生,通过其受体(CCR-3)而选择性地诱导EOS在肺内黏附、募集和脱颗粒。在EOS趋化、募集于肺组织内的过程中，IL-5与Eotaxin起着协同的作用；在缺乏IL-5时，由于EOS供应来源不足．Eotaxin单独对EOS的促趋化作用明显减弱。而抗IL-5抗体能显著抑制气道EOS聚集，但对AHR的影响有完全不同的结论．其机理尚不明了。通过基因、蛋白合成酶、抗体及受体等环节抑制IL-5和Eotaxin的产生和作用可能是治疗哮喘的有效途径之一。     

IL-17与支气管哮喘

白介素 17(IL 17)是由活化CD4 + 、CD4 5RO+ 记忆T细胞产生的一种细胞因子。IL 17在体外能激活支气管哮喘 (哮喘 )患者的成纤维细胞 (FB)、巨噬细胞产生并分泌一系列与气道重构有关的细胞因子 ,如GM CSF、TNF α、IL 1β等 ,还能与FB一起支持CD34+ 造血前体细胞增殖和分化成熟为中性粒细胞 ,是T细胞诱导的炎症反应的早期启动因素 ,可能参与哮喘的发病与气道重构。本文综述了近年来这方面的进展     

MicroRNA-31对 HIV感染者CD4+ T细胞CD69表达的影响及机制

目的　探讨微小RNA（microRNA, miR）-31对HIV感染者CD4+ T细胞表面CD69表达的影响及作用机制。方法　通过流式细胞仪分析健康对照与HIV感染者的CD4+ T细胞活化后CD69表达情况。在健康人外周血单个核细胞中转染antagomir-miR-31抑制miR-31表达，观察CD4+ T细胞活化后CD69表达情况。采用生物信息学方法预测miR-31靶基因及相关通路，并在293T细胞系中过表达和抑制miR-31，通过实时荧光定量PCR检测相关靶基因的表达。结果　与健康对照相比，HIV感染者CD4+ T细胞在抗-CD3/CD28抗体刺激活化后CD69表达更低。抑制miR-31表达后，CD4+ T细胞活化时CD69的表达与对照相比显著下降。miR-31低表达后T细胞活化信号通路KSR2和DUSP7表达升高。结论　miR-31可以有效调节CD4+ T细胞表面CD69的表达，对HIV感染者早期免疫活化起重要作用。     

哮喘的基因治疗

哮喘是由环境及基因多因素共同作用而导致的一种以气道炎症及气道高反应性(AHR)为特征的全球性疾病。其中T细胞调控的免疫介质(细胞因子、炎症介质)的释放在哮喘的发病中起关键的作用。本文从哮喘的免疫学发病机制入手,综述了哮喘的基因治疗方法。1免疫学发病机制Th1、Th2细胞在体内呈现一种相互约束,相互消长的平衡状态。多种途径导致的抗原介导的CD+4T细胞向Th2细胞的分化,使Th1/Th2比例失衡,这种分化导致IgE的产生,嗜酸粒细胞(EOS)的募集,活化以至于气道上皮损伤及AHR。与CD+4T细胞分化密切相关的介质有IL12、IL4、IL5、干扰…     

IL-5、Eotaxin与支气管哮喘

IL 5是由CD4 + T细胞TH2 亚型产生的一种糖蛋白 ,哮喘时明显增多 ,能促进骨髓池中的嗜酸粒细胞 (EOS)分化、成熟、增殖并进入血循环 ,通过上调sICAM 1而使EOS趋化、黏附、渗出到气道组织 ,为EOS浸润提供充足的细胞来源 ,是EOS趋化和募集的必要因素 ,还可促使其活化释放各种毒性蛋白 ,参与过敏性哮喘过程并使气道反应性明显增高 ,还能抑制EOS的凋亡而延长其存活时间。Eotaxin是cc趋化因子家族成员之一 ,由结构性细胞和渗出性炎症细胞产生 ,通过其受体 (CCR 3)而选择性地诱导EOS在肺内黏附、募集和脱颗粒。在EOS趋化、募集于肺组织内的过程中 ,IL 5与Eotaxin起着协同的作用 ;在缺乏IL 5时 ,由于EOS供应来源不足 ,Eotaxin单独对EOS的促趋化作用明显减弱。而抗IL 5抗体能显著抑制气道Eos聚集 ,但对AHR的影响有完全不同的结论 ,其机理尚不明了。通过基因、蛋白合成酶、抗体及受体等环节抑制IL 5和Eotaxin的产生和作用可能是治疗哮喘的有效途径之一。     

细胞毒T淋巴细胞抗原-4与支气管哮喘

T细胞激活在哮喘形成和发展过程中起着主导作用。T细胞激活需要T细胞受体-APC抗原肽复合物与B7与CD28/CTLA-4共刺激途径共同作用完成。细胞毒T淋巴细胞抗原-4（CTLA-4）在阻止T细胞的活化增殖，调节CD4^ 与CD8^ T细胞的平衡，影响Th2分化中发挥主导作用。支气管哮喘存在细胞因子紊乱，通过对CTLA-4的研究可望为支气管哮喘的免疫治疗研究开辟新的路径。     

嗜酸粒细胞在气道激活机制中的研究进展

支气管哮喘是一种以嗜酸粒细胞（eosinophils,EOS）和肥大细胞浸润、气道高反应性为主要病理生理特征的慢性气道炎症,其中EOS在气道的激活对疾病的发生发展起着关键作用。气道中的EOS主要来源于外周血,极小部分来源于气道内的嗜酸粒细胞前体祖细胞,前者早在外周血中便在内皮细胞的作用下开始启动激活,之后气道上皮细胞通过表达细胞因子IL-3、IL-6、IL-8、RANTES及EOS重要的趋化因子eotaxin等趋化其向气道迁移。两种来源的EOS在气道的激活都是各种炎症细胞、细胞因子、趋化因子相互作用的结果 ：一方面,气道内的Th2细胞、Th1细胞、Th17细胞、肥大细胞等通过分泌IL-4、IL-5、IL-17等细胞因子促进EOS的激活;另一方面,各种细胞因子如PAF、IL-33、IL-7等也通过各种途径激活EOS并维持EOS的活性。本文就目前国内外关于EOS在气道激活机制的研究情况作一综述。     

环孢素A对支气管哮喘豚鼠肺内嗜酸粒细胞凋亡及Fas表达的影响

支气管哮喘（简称哮喘）是一种涉及多种炎性细胞的慢性炎症性疾病，其中嗜酸粒细胞（EOS）是关键的效应细胞。EOS凋亡异常在哮喘气道炎症发生中的作用已有研究。糖皮质激素（简称激素）诱导EOS凋亡可能为其抗哮喘气道炎症的重要机制。但激素对抵抗型哮喘的治疗是临床上面临的一大难题。初步临床观察表明，小剂量环孢素A（CSA）可以使激素抵抗型哮喘患者肺功能明显改善而激素用量减少，但其确切机制尚不清楚。我们的实验通过环孢素A对哮喘豚鼠肺内EOS凋亡及Fas表达的影响，来揭示环孢素A治疗哮喘的可能机制。     

老年支气管哮喘病人CD4^＋T细胞的活化状态

支气管哮喘 (简称哮喘 )是气道的一种变态反应性炎症。在变态反应的形成过程中 ,T淋巴细胞起着很重要的调控作用。尤其是 CD4 T细胞 ,被认为具有主要辅助活化调节作用。CD2 5、CD30均为 T细胞活化的主要表达标志 ,过去对 CD2 5研究较多 ,而 CD30在哮喘病人 CD4 T细胞的表达情况鲜有报道。本研究通过检测外周血 CD4 T细胞 CD2 5、CD30表达水平 ,了解老年哮喘病人 CD4 T细胞的活化状态。1　材料与方法1.1　 检测对象　 2 6例未用激素的老年哮喘急性发作期病人为我院呼吸内科门诊就诊者 ,诊断符合 1997年青岛全国哮喘病会议修订的哮…     

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.     

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.     

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.