类风湿关节炎患者外周血B淋巴细胞共刺激分子的表达及其意义

目的 初步探讨类风湿关节炎(RA)患者免疫功能紊乱的机制。方法 采用流式细胞仪检测RA患者外周血B淋巴细胞共刺激分子CD80、CD86、CD40的表达并用ELISA检测RA患者血清和关节滑膜液中Th1细胞分泌的细胞因子白细胞介素(IL)-2、干扰素-γ和Th2细胞分泌的细胞因子IL-6、IL-10的水平。结果 RA患者外周血B淋巴细胞CD86表达比正常对照组明显下降(P＜0．01),B淋巴细胞CD40表达比正常对照组明显增多(P＜0．05),而B淋巴细胞CD80表达与正常对照组之间差异无显著性(P＞0．05),同时RA患者血清及滑膜液中IL-2、干扰素-γ的水平比正常对照组明显升高(P＜0．01或P＜0．05),而IL-6、IL-10的水平降低(P＜0．01或P＜0．05)。结论 B淋巴细胞共刺激分子CD86、CD40的异常表达可能与RA患者Th1／Th2细胞分泌的细胞因子失衡密切相关,这将为临床治疗RA提供新的思路。     

趋化因子受体CCR4在活动期类风湿关节炎患者外周血CD4+T细胞表达的研究

目的 探讨活动期类风湿关节炎(aRA)患者趋化因子受体CCR4在外周血CD4+T细胞的表达及其意义,并对该表达与血清重要细胞因子水平的相关性进行研究.方法流式细胞计数方法对12例aRA患者和10名健康对照者外周血CD4+T细胞表面CCR4的表达情况进行检测;酶联免疫吸附试验(ELISA)方法检测患者血清肿瘤坏死因子(TNF)-α、白细胞介素(IL)-10及干扰素(IFN)-γ的水平并记录患者相关临床及实验室资料.分析及评价aRA患者外周血淋巴细胞中CD4+CCR4+T细胞百分数(CD4+CCR4+T%)与TNF-α、IL-10、IFN-γ的血清水平及临床指标的相关性.结果 aRA组外周血CD4+CCR4+T%明显高于健康对照组(P＜0.01).aRA组血清TNF-α(P＜0.01)、IL-10(P＜0.01)及IFN-γ(P＜0.01)水平明显高于健康对照组.在检测的细胞因子中,aRA患者血清IL-10水平与CD4+CCR4+T%呈明显正相关关系(r＝0.66,P＜0.05).在临床指标中,CD4+CCR4+T%与aRA患者Lunsbury关节指数、血沉、C反应蛋白及血小板计数呈明显正相关关系(P＜0.05).结论 CCR4在CD4+T细胞趋化至病变关节过程中可能发挥重要作用;外周血CD4+CCR4+T%与血清IL-10水平密切相关;该百分数可以作为临床评价RA活动性的一个敏感指标.     

类风湿关节炎患者外周血CD4 T细胞关节局部趋化机制

目的探讨类风湿关节炎(RA)患者外周血CD4 T细胞比例变化情况及其对关节局部趋化的机制。方法流式细胞术分析RA患者外周血单个核细胞(PBMC)中CD4 T细胞的比例,并分析CD4 T细胞比例与RA疾病活动性评分系统(DAS28)评分间的关系。激光共聚焦方法检测RA患者滑膜局部浸润CD4 T细胞情况。流式细胞术分析RA患者CD4 T细胞表面趋化因子受体表达情况。结果与对照组相比,RA患者外周血PBMC中CD4 T细胞的比例显著降低(P0.01),且RA患者外周血CD4 T细胞比例与DAS28评分呈明显负相关(r=-0.753 0,P=0.001 2)。关节局部CD4 T细胞浸润的激光共聚焦结果显示,与对照组相比,RA患者滑膜中具有更多的CD4 T细胞浸润。趋化因子受体分析结果显示,RA患者外周血CD4 T细胞表面CCR5、CXCR1和CXCR3的表达显著升高(P0.01)。结论 RA患者外周血CD4 T细胞表面表达升高的CCR5、CXCR1和CXCR3可能参与外周血CD4 T细胞向滑膜局部的趋化。     

类风湿关节炎患者CD4~+CD25~+调节性T细胞和趋化因子受体表达及相关性

目的探讨类风湿关节炎(RA)患者外周血中CD4+CD25+表达率及调节性T细胞上趋化因子受体表达水平及相关性。方法检测活动期RA组和健康对照组调节性T细胞的表达频率;判断T细胞表达率、T细胞上趋化因子受体CCR4的表达水平与RA疾病活动性指标的相关性;判断血清肿瘤坏死因子(TNF)-α、IL-10、IL-17及干扰素(IFN)-γ等与CD4+上趋化因子受体CCR4+表达水平的相关性。结果活动期RA患者T细胞表达率与趋化因子受体表达水平较健康对照组低;T细胞表达率和趋化因子受体表达水平与RA疾病活动度存在显著相关;与血清IL-10、IL-17水平呈显著正相关,与IFN-γ呈显著负相关,而与血清TNF-α则无明显相关。结论 T细胞表达率和趋化因子受体表达水平与RA疾病活动度存在显著相关,CD4+CD25+T细胞上趋化因子受体表达参与RA发病过程。     

类风湿关节炎患者血清和滑膜骨桥蛋白的测定

目的 研究骨桥蛋白(OPN)在类风湿关节炎(RA)患者外周血中的浓度变化及在滑膜的表达,探讨OPN在RA患者中的发病机制.方法 收集91例RA患者以及29名正常对照人群临床资料和血清,用酶联免疫吸附试验(ELIsA)方法检测OPN在RA患者外周血中的浓度,分析其变化和RA临床及实验室指标的关系.收集7例RA患者和1名正常对照的滑膜组织,用免疫组织化学的方法观察OPN的表达情况.结果 与正常对照组相比,活动组和非活动组的RA患者外周血中OPN水平均明显升高(p＜0.01),且与RA患者的部分临床指标有相关性:与压痛关节数(r=0.435,P=0.005)、关节的X线分期(r=-0.415,P=0.007)、关节功能(r=0.394,P=0.012)显著相关.OPN在RA滑膜组织大量表达,而在正常对照仅见OPN的少量表达.结论 OPN在RA患者外周血中浓度显著升高,且在滑膜表达明显,OPN可能与RA滑膜增生、骨侵蚀有关.     

Th17细胞/调节性T细胞偏倚在类风湿关节炎中的意义

目的 探讨白细胞介素(IL)-17+CD4+炎症性T细胞(Th17细胞)和Foxp3+CD4+调节性T细胞在类风湿关节炎(RA)的相互关系及可能机制.方法 采用前瞻性随机开放研究.测定RA患者外周血IL-17+CD4+T细胞及Foxp3+CD4+T细胞的比例变化及其相关细胞因子转化生长因子(TGF)-β、IL-6、IL-23和IL-17水平.结果 RA患者外周血IL-17+CD4+T细胞明显升高(P<0.01),而Foxp3+CD4+T细胞明显降低(P<0.01).同时,血清中IL-6、IL-23和IL-17水平明显升高(均P<0.01),而TGF-β水平无明显变化(P>0.05).结论 RA患者Th17细胞数量增高,而调节性T细胞数量减少,体内相关细胞因子的变化是引起上述改变的重要原因.     

Th17细胞/调节性T细胞偏倚在类风湿关节炎中的意义

目的 探讨白细胞介素(IL)-17+CD4+炎症性T细胞(Th17细胞)和Foxp3+CD4+调节性T细胞在类风湿关节炎(RA)的相互关系及可能机制.方法 采用前瞻性随机开放研究.测定RA患者外周血IL-17+CD4+T细胞及Foxp3+CD4+T细胞的比例变化及其相关细胞因子转化生长因子(TGF)-β、IL-6、IL-23和IL-17水平.结果 RA患者外周血IL-17+CD4+T细胞明显升高(P<0.01),而Foxp3+CD4+T细胞明显降低(P<0.01).同时,血清中IL-6、IL-23和IL-17水平明显升高(均P<0.01),而TGF-β水平无明显变化(P>0.05).结论 RA患者Th17细胞数量增高,而调节性T细胞数量减少,体内相关细胞因子的变化是引起上述改变的重要原因.     

Th17细胞/调节性T细胞偏倚在类风湿关节炎中的意义

目的 探讨白细胞介素(IL)-17+CD4+炎症性T细胞(Th17细胞)和Foxp3+CD4+调节性T细胞在类风湿关节炎(RA)的相互关系及可能机制.方法 采用前瞻性随机开放研究.测定RA患者外周血IL-17+CD4+T细胞及Foxp3+CD4+T细胞的比例变化及其相关细胞因子转化生长因子(TGF)-β、IL-6、IL-23和IL-17水平.结果 RA患者外周血IL-17+CD4+T细胞明显升高(P<0.01),而Foxp3+CD4+T细胞明显降低(P<0.01).同时,血清中IL-6、IL-23和IL-17水平明显升高(均P<0.01),而TGF-β水平无明显变化(P>0.05).结论 RA患者Th17细胞数量增高,而调节性T细胞数量减少,体内相关细胞因子的变化是引起上述改变的重要原因.     

Th17细胞/调节性T细胞偏倚在类风湿关节炎中的意义

目的 探讨白细胞介素(IL)-17+CD4+炎症性T细胞(Th17细胞)和Foxp3+CD4+调节性T细胞在类风湿关节炎(RA)的相互关系及可能机制.方法 采用前瞻性随机开放研究.测定RA患者外周血IL-17+CD4+T细胞及Foxp3+CD4+T细胞的比例变化及其相关细胞因子转化生长因子(TGF)-β、IL-6、IL-23和IL-17水平.结果 RA患者外周血IL-17+CD4+T细胞明显升高(P<0.01),而Foxp3+CD4+T细胞明显降低(P<0.01).同时,血清中IL-6、IL-23和IL-17水平明显升高(均P<0.01),而TGF-β水平无明显变化(P>0.05).结论 RA患者Th17细胞数量增高,而调节性T细胞数量减少,体内相关细胞因子的变化是引起上述改变的重要原因.     

Th17细胞/调节性T细胞偏倚在类风湿关节炎中的意义

目的 探讨白细胞介素(IL)-17+CD4+炎症性T细胞(Th17细胞)和Foxp3+CD4+调节性T细胞在类风湿关节炎(RA)的相互关系及可能机制.方法 采用前瞻性随机开放研究.测定RA患者外周血IL-17+CD4+T细胞及Foxp3+CD4+T细胞的比例变化及其相关细胞因子转化生长因子(TGF)-β、IL-6、IL-23和IL-17水平.结果 RA患者外周血IL-17+CD4+T细胞明显升高(P<0.01),而Foxp3+CD4+T细胞明显降低(P<0.01).同时,血清中IL-6、IL-23和IL-17水平明显升高(均P<0.01),而TGF-β水平无明显变化(P>0.05).结论 RA患者Th17细胞数量增高,而调节性T细胞数量减少,体内相关细胞因子的变化是引起上述改变的重要原因.     

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.