自体外周血干细胞移植治疗难治性系统性红斑狼疮的临床研究

目的探讨自体外周血干细胞移植(APBSCT)治疗难治性系统性红斑狼疮(SLE)的临床疗效。方法对难治性SLE患者进行APBSCT治疗。采用环磷酰胺(CTX) 粒细胞集落刺激因子(G-CSF)方案动员,CS-3000血细胞分离机采集外周血干细胞并保存于-80℃冰箱;用CTX50mg/(kg.d)×3～4d方案预处理后,解冻后回输冻存的干细胞的治疗方法。观察APBSCT前后临床表现及免疫学指标的变化。结果动员后获得单个核细胞数(MNC)(3.383～3.704)×108/kg;CD34 细胞数(4.4～11.12)×106/kg。3例均获得造血重建,中性粒细胞>0.5×109/L、血小板>20×109/L的中位数时间分别是8.3d、10d。移植后患者临床症状消失,1例并肾功能不全、难治性高血压和重度贫血的患者移植后恢复正常。3例患者自身抗体转阴或滴度减低,尿蛋白定性消失,SLE疾病活动指数(SLE-DAI)由移植前的平均15分下降为移植后6个月的平均4分。结论APBSCT治疗难治性SLE安全有效,近期疗效好,远期疗效有待进一步观察。     

免疫清除性化疗结合自体外周血造血干细胞移植治疗重症系统性红斑狼疮

目的 观察免疫清除性化疗结合自体外周血造血干细胞移植（移植）治疗重症系统性红斑狼疮（SLE）的疗效及安全性。方法 重症SLE4例，分别合并狼疮性肾炎，狼疮脑，狼疮心或股骨头坏死，干细胞的动员采用环磷酰胺加重组人粒细胞集落因子（G－CSF）；预处理为回输前3天每天应用环磷酰胺50mg/kg 回输后3天每天应用抗胸腺细胞球蛋白（ATG）5mg/kg。观察移植前后临床症状，体征，狼疮相关抗体等指标的改变，并动态观察移植后免疫功能的重建。结果 移植后患者的临床症状完全缓解，狼疮相关抗体全部转阴，移植后患者的免疫功能均明显降低，约半年后恢复正常，但不伴有临床症状的复发。结论 免疫清除性化疗结合自体外周血造血干细胞移对难治性SLE有明显的疗效，尤其适用对各种药物治疗无效者，治疗是安全的，远期疗效还需长期随访。     

自体外周血造血干细胞移植治疗系统性红斑狼疮

目的：探讨自体外周血造血干细胞（APBSCT）治疗系统性红斑狼疮（SLE）的临床效果。方法：采集经用环磷酰胺（CTX）2000mg/m^2静脉注射和粒细胞集落刺激因子（G－CSF）250ug/d皮下注射动员的外周血造血干细胞，预处理CTX48mg.kg^-1.d^-1，连续静脉滴注3d，回输干细胞后用抗胸腺细胞球蛋白（ATG）13．5mg/kg，体内去细胞，分3d静脉滴注，用G－CSF刺激升高白细胞，观察APBSCT前后免疫指标与临床表现，结果：APBSCT后患者的临床表现基本消失，免疫指标正常，抗体转阴，结论：APBSCT治疗SLE有较好的疗效，远期疗效还需长期随访观察。     

自体外周血造血干细胞移植治疗系统性红斑狼疮的临床观察

目的 探讨自体外周血造血干细胞移植(APBSCT)治疗难治性系统性红斑狼疮(SLE)的临床疗效和安全性.方法 10例难治性SLE患者接受APBSCT治疗,应用环磷酰胺(CTX)2～4 g/m2和粒细胞集落刺激因子5～10 μg·kg-1·d-1行外周血造血干细胞动员;预处理包括CTX(50 mg·kg-1·-1,-6～-3 d)和抗胸腺细胞球蛋白(ATG,15～20 mg·kg-1·d-1,-2 d、-1 d、1 d、2 d).患者输注的CD34+细胞＞2×106/kg.评估治疗前后临床表现、SLE疾病活动指数(SLEDAI)和免疫指标的变化.结果 APBSCT后10例SLE患者的临床症状缓解,SLEDAI评分降低,均获得造血重建,中性粒细胞＞0.5×109/L的中位数时间为9.5 d,血小板＞20×109/L中位数时间是11 d;尿蛋白减少或消失,抗核抗体滴度减低或转阴,补体水平升高;移植相关的并发症有:2例败血症,2例巨细胞病毒感染,1例出现肾毒性,3例急性左心衰竭,3例心律失常,无移植相关死亡.结论 APBSCT能够改善SLE患者的疾病活动和免疫学指标,是一种有效的治疗难治性SLE的方法,但远期疗效需进一步观察.     

自体骨髓干细胞移植治疗系统性红斑狼疮的临床研究

目的：探讨自体骨髓干细胞移植(ABMSCT)对系统性红斑狼疮(SLE)的临床疗效。方法：3例患者采集自体骨髓移植CD34^ 造血干细胞，预处理用环磷酰胺(CTX)60mg／kg连续2d静脉滴注，马法兰140mg／m^2分次口服，抗CD3、CD8单抗各5mg／d连续5d静脉滴注，用粒细胞集落刺激因子(G-CSF)协助造血及免疫重建，用间接免疫荧光法检测抗核抗体、放免法测抗DNA抗体、流式细胞仪测淋巴细胞亚群，观察ABMSCT前后临床表现和免疫学指标的变化。结果：ABMSCT后患者的临床症状明显缓解，异常免疫学指标恢复正常，抗体全部转阴。结论：ABMSCT对SLE有较好的近期疗效，远期疗效还需长期随访。     

自体外周血造血干细胞移植治疗难治性系统性红斑狼疮

目的:探讨自体外周血造血干细胞移植(APBSCT)治疗难治性系统性红斑狼疮(SLE)的临床疗效。方法:用APBSCT治疗4例难治性SLE。干细胞动员应用环磷酰胺(CTX)4g/m2,分两天应用和粒细胞集落刺激因子(G-CSF)5~10μg/kg·d-1;预处理方案包括CTX(50mg/kg·d-1,-6、-5、-4、-3d),抗胸腺细胞球蛋白(ATG15~20mg/kg·d-1,-2、-1、 1、 2d)。结果:4例患者均获得造血重建,中性粒细胞>0.5×109/L,血小板>20×109/L的中位数时间分别是9d,10d;SLE的临床表现明显减轻,尿蛋白减少或消失,自身抗体转阴或滴度减低,泼尼松用量<10mg/d;无移植相关死亡。结论:APBSCT治疗难治性SLE近期疗效显著,造血重建恢复迅速,安全有效,远期疗效尚需进一步观察。     

自体骨髓干细胞移植治疗系统性红斑狼疮的临床研究

目的 探讨自体骨髓干细胞移植（ＡＢＭＳＣＴ）对系统性红斑狼疮（ＳＬＥ）的疗效。方法 采集自体骨髓移植ＣＤ３４＾＋造血干细胞,预处理用环磷酰胺（ＣＴＸ）６０ｍｇ／ｋｇ连续２天静滴,马法兰１４０ｍｇ／ｍ＾２分次口服,用格拉诺赛特（Ｇ－ＣＳＦ）刺激粒细胞的恢复,用间接免疫荧光法检测抗核抗体、放免法测抗ＤＮＡ抗体、流式细胞仪测淋巴细胞亚群,观察ＡＢＭＳＣＴ前后临床表现和免疫学指标的变化．结果 ＡＢＭＳＣＴ     

自体外周血造血干细胞移植治疗系统性红斑狼疮的初步观察

目的探讨自体外周血造血干细胞移植(APBSCT)治疗系统性红斑狼疮(SLE)的可行性及临床效果。方法对8例女性难治性SLE病人进行APBSCT。采集的干细胞的单个核细胞计数平均为1.6×108/kg[(0.07～2.6)×108/kg]。预处理方案为环磷酰胺(50mg·kg-1·d-1,-5～-2d)静脉滴注及兔抗人淋巴细胞免疫球蛋白(10mg·kg-1·d-1,-3～-1d)静脉滴注。从移植前后皮肤红斑的变化,尿的改变,SLE相关的免疫指标的变化,移植后造血重建情况,移植的并发症等方面进行评价。结果8例病人均获得成功植入,外周血白细胞总数>1.0×109/L的平均时间为9.5d,中性粒细胞计数>0.5×109/L的平均时间为10d,白细胞总数恢复正常的平均时间为14d,血小板计数>50×109/L的平均时间为30d,血红蛋白含量平均在移植后第28天升至100g/L。移植后SLE临床症状均消失,尿蛋白转阴,自身抗体大部分转阴。移植相关并发症中,均出现血清病样预处理反应,2例出现严重的低血压;4例有出血性膀胱炎;2例出现败血症;4例发生霉菌感染;2例发生间质性肺炎。随访时间2个月～2.5年。结论APBSCT治疗SLE有较好的近期疗效,但观察病例及时间有限,远期疗效还需更长时间的观察。对药物治疗难以奏效的SLE病例,该法不失为一种更佳的选择。     

系统性红斑狼疮患者自体外周血造血干细胞移植前后粒细胞形态变化

目的观察25例系统性红斑狼疮患者自体外周血造血干细胞移植前后的粒细胞形态变化。方法采用环磷酰胺和重组人粒细胞集落刺激因子（rhGM-CSF）动员后获得的外周血造血干细胞,经马利兰、环磷酰胺、抗人淋巴细胞球蛋白、甲基强的松龙预处理后,回输自体外周血干细胞,用rhGM-CSF刺激恢复造血,注射rhGM-CSF前后采集静脉血制备血涂片,pH 6.4~6.8条件下瑞特-姬姆萨混合染色后在油镜下观察中性粒细胞形态,同时进行中性粒细胞碱性磷酸酶（NAP）染色,pH 5.4条件下姬氏染色观察中毒颗粒。结果应用rhGM-CSF治疗前1 d中性粒细胞形态无明显异常,中毒颗粒、NAP积分值均在正常范围;应用rhGM-CSF治疗后中毒颗粒、NAP积分明显增高,96%的中性粒细胞胞体偏大,胞浆内见＂中毒＂性颗粒、空泡数量增加。结论系统性红斑狼疮患者应用rhGM-CSF可引起外周血中性粒细胞出现明显的形态学改变。     

自体外周血干细胞移植治疗系统性红斑狼疮过程中并发红色酵母菌败血症一例

近年来造血干细胞移植(HSCT)已成为治疗重症难治性系统性红斑狼疮(SLE)的一种新方法,欧洲风湿病协会和欧洲骨髓移植协作组自身免疫病数据库报道,SLE总的移植相关死亡率约为9%,死亡原因主要有：疾病进展、感染、出血和器官毒性。患者死于条件致病性微生物感染者中以念珠菌属、结核分枝杆菌、巨细胞病毒感染最为常见。而SLE在自体外周血干细胞移植(APBSCT)过程中并发红色酵母菌败血症国内、外未见报道,现将近期经治的1例报告如下。     

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.     

Language of CTO interventions – Focus on hardware

The knowledge of variety of chronic total occlusion (CTO) hardware and the ability to use them represents the key to success of any CTO interventions. However, the multiplicity of CTO hardware and their physical character and the terminology used by experts create confusion in the mind of an average interventional cardiologist, particularly a beginner in this field. This knowledge is available but is scattered. We aim to classify and compare the currently used devices based on their properties focusing on how physical character of each device can be utilized in a specific situation, thus clarifying and simplifying the technical discourse.