上海地区老年人雌激素受体基因多态性与骨密度关系的研究

目的 了解雌激素受体（ER）基因多态性在中国老年人群中的分布，并进一步研究其与骨密度的关系。方法 通过聚合酶链反应－限制性片段彻底多态性（PCR－RFLP）方法分析了413例无亲缘关系的上海地区老年男女居民的ER基因型，并用双能X线吸收仪测定了其中288例骨密度。结果 413例研究对象中pp型、Pp型、PP型频率分别为0．346，0．501及0．153，p与P等位基因频率分别为0．597，0．403，男女性之间ER基因型分布频率无明显区别（P＞0．5），中国人群中以Pp型为多见。组间方差分析显示这三种基因型的各部位骨密度无显差别。结论 ER基因多态性与骨密度无相关关系。     

绝经妇女雌激素受体基因PvuⅡ酶切位点多态性与骨密度的关系

目的 从分子生物水平探讨绝经后健康妇女雌激素受体（ER）基因PvuⅡ酶切位点多态性与骨密度的关系。方法 选择绝经后健康无亲缘关系妇女237例,运用双能X线吸收骨密度仪及聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法分析ER基因PvuⅡ酶切位点多态性与骨密度的关系。结果 237例绝经后健康妇女PP、Pp及pp基因型频率分别为19.8%、44.3%及35.9%。ANOVA分析显示,Troch部位骨密度与ER基因PvuⅡ酶切位点多态性显著相关（P=0.0106）;多元逐步回归分析发现,ER基因多态性与腰椎及Troch部位的骨密度变化相关性无统计学显著性意义,P值分别为0.0998、0.0548。结论 中国上海地区绝经后健康妇女ER基因多态性与股骨Troch部位的骨密度显著相关,p等位基因具有一定的骨量保护作用。     

老年骨质疏松性骨折与CYP11A1基因rs900798位点多态性的相关性

目的探讨老年骨质疏松性骨折与CYP11A1基因rs900798位点多态性相关性。方法选择老年骨质疏松性骨折患者90例作为研究组;另选择同期单纯老年骨质疏松患者80例作为对照组。采用日立7600型全自动生化分析仪及配套试剂盒严格依据试剂盒说明书标准测定骨钙素(BGP)、Ⅰ型原骨胶原蛋白N-端肽(sCTX)和碱性磷酸酶(ALP)含量;采用双能X线吸收仪测定股骨颈和腰椎(L2～4)骨密度;采用PCR法检测CYP11A1基因rs900798位点多态性,采用SNaPshot技术进行基因分型。比较两组骨代谢标志物和CYP11A1基因rs900798位点等位基因分布频率与基因型频率变化,不同基因型骨代谢标志物和骨密度变化。结果研究组BGP含量显著低于对照组,而sCTX和ALP含量显著高于对照组,差异有统计学意义(均P0.05)。两组等位基因频率和基因型频率比较差异无统计学意义(P0.05)。不同基因型血清BGP、sCTX和ALP含量比较差异无统计学意义(P0.05)。不同基因型股骨颈和腰椎(L2～4)骨密度比较差异无统计学意义(P0.05)。结论老年骨质疏松性骨折与CYP11A1基因rs900798位点多态性无明显相关性。     

雌激素受体基因多态性与女性类风湿关节炎相关性的研究

目的分析雌激素受体(ER)基因XbaⅠ和PvuⅡ酶切多态性在女性类风湿关节炎(RA)中的分布,探讨其与人类白细胞抗原(HLA)-DRβ1*04基因亚型、类风湿因子(RF)以及RA患者临床表现的关系。方法采用聚合酶链反应-限制性片断长度多态性(PCR-RFLP)技术,对81例女性RA患者和146名女性正常对照者的ER基因(XbaⅠ、PvuⅡ位点)进行分型,并计算基因分布频率。分析患者的HLA-DRβ1*04基因亚型、RF以及临床表现与ER基因多态性之间的关系。结果女性RA患者的ER基因X、P基因频率均明显高于健康对照组,ER基因的XX和PP基因亚型的阳性率分别高于正常对照组(P<0.05)。而RA患者的xx基因亚型的阳性率明显低于健康对照组(P<0.05)。RA患者XXPP基因型的阳性率明显高于健康对照组,而xxpp基因型的阳性率明显低于健康对照组(P<0.05)。携带PP基因型的RA患者HLA-DRβ1*04基因亚型的阳性率明显升高(P<0.05)。ER基因中pp基因型、XXpp和xxPP基因型的患者关节受累数明显增高(P<0.05)。结论女性RA患者ER基因的X和P的基因频率表达明显增高。ER基因酶切多态性分析中,XX、PP及XXPP基因型可能与女性RA的易感性相关。PP基因型可能与HLA-DRβ1*04基因有一定的相关性,pp基因型、XXpp和xxPP基因型可能与RA关节病变的程度相关。     

糖尿病维生素D受体基因多态性与骨密度相关性研究

目的　探讨糖尿病 (DM )患者维生素D受体 (VDR)基因多态性与骨密度 (BMD)及骨转化的关系。方法　采用PCR RFLP技术 ,检测 6 8例 2型DM患者、5 4例 1型DM患者和 6 2例健康人的VDR基因型。并采用双能X线吸收法测BMD ,放免法测血清BGP、降钙素和 2 5 (OH)D3 ,免疫放射法测血清完整PTH及Ⅰ型胶原羧基末端前肽。结果　 (1)DM组VDR基因型分布与健康组差异无显著性 ;(2 )健康组AA基因型者腰椎和大转子BMD高于aa型 ,股骨颈和Ward′s三角BMD高于aa和Aa型 (P <0 .0 5 ) ,而 2型DM组Aa基因型者股骨颈和大转子BMD高于aa型 ,1型DM组Aa基因型者仅股骨颈BMD高于aa型 (P <0 .0 5 ) ;(3)VDR基因TaqⅠ位点多态性与BMD无明显相关性。结论　DM患者VDR基因ApaⅠ位点的多态性与BMD存在相关性。     

细胞毒性T淋巴细胞相关抗原4基因多态性与中国汉族人1型糖尿病、自身免疫性甲状腺病的相关性研究

目的 探讨细胞毒性T淋巴细胞相关抗原4（CTLA－4）基因外显子1的49位点A／G多态性与中国汉族人1型糖尿病、自身免疫性甲状腺病（AITDs）的关系。方法 对33例典型1型糖尿病患者、57例成人晚发自身免疫性糖尿病患者（LADA）、122例自身免疫甲状腺疾病患者（AITDs）和84例健康对照者采用聚合酶链反应－限制性片段长度多态性（PCR－RFLP）技术分析CTLA－4基因外显子1的49位点基因型。结果 1型糖尿病患者的CTLA－4G等位基因频率显著高于对照组（P＝0．0005）;胰岛细胞抗体和谷氨酸脱酶脱羧酶抗体阳性率与G无明显相关性。AITDs患者CTLA－4G等位基因频率高于对照组（P＜0．0001）;Graves病组按性别分层分析后发现G等位基因在不同性别的分布差异无显著性。12例AITDs患者同时合并糖尿病,其CTLA－4G等位基因频率与单纯AITDs患者相比差异无显著性。结论 CTLA－4基因外显子1多态性与中国汉族人1型糖尿病、AITDs有关,G等位基因是1型糖尿病、AITDs的危险因素之一。     

ERα基因多态性与Alzheimer病智能衰退的相关分析

目的 探讨中国汉族人群中雌激素受体(ER)α基因酶切多态性与散发性Alzheimer氏病(SAD)的发病及其智能衰退的相关性.方法 采用聚合酶链反应限制片段长度多态性方法,检测63例AD患者及70例健康对照老年人的ERαPvuⅡ、XbaⅠ酶切基因多态性;采用MMSE、ADL量表观察38例AD患者6个月的智能衰退状况与ERα基因多态性的关系.结果 AD组ERα等位基因x的频率、Pp、xx、Ppxx型较对照组明显增加,而PP、XX、PPXX型明显减少(P＜0.05);XbaI酶切基因多态性xx、Ppxx与AD发病明显正相关(OR分别为2.34,95%CI 1.47～4.09和 1.79,95%CI 1.26～3.12)(P＜0.05).Pp与AD发病无明显相关(OR 1.58,95%CI 1.15～2.12).ERа基因xx、Ppxx型与AD的智能衰退无明显相关性.结论 雌激素α受体xx或Ppxx基因型是SAD发病的危险因素,但与AD的智能衰退无明显相关性;ERαXbaⅠ基因酶切多态性xx型可能与中国汉族SAD的发病具有相关性.     

胰岛素受体底物-2基因多态性与2型糖尿病的相关性研究

目的 研究北京地区汉族人群中胰岛素受体底物-2（IRS-2）基因密码子1057g/a多态性与2型糖尿病及其中间表型的相关性。方法 选取北京地区的中国汉族患者110例，对照组80例。用聚合酶链反应-限制性内切酶片段长度多态性（PCR-RFLP）的方法检测IRS-2基因密码了1057g/a多态性。结果 （1）IRS-2基因密码子1057g/a多态性的a等位基因频率在糖尿病组和对照组中分别为26.4%和36.3%。（2）糖尿病组aa基因型频率明显低于对照组，分别为5.5%和18.7%(P=0.016),Logistic相关分析表明：aa基因型为2型糖尿病的保护性因素，OR值为0.28(95%CI=0.09-0.91,P=0.03)。（3）不同基因型组间血压、血脂，胰岛素抵抗指数及胰岛β细胞功能指数等均差异无显著性。结论 中国北方地区汉族人群中IRS-2基因密码子1057g/a多态性的aa基因型在2型糖尿病中明显减少。但2型糖尿病各种中间表型自欺欺人持征在不同基因型间均无明显差异。上述结果有待于进一步扩大样本量来加以确认。     

脂联素基因SNP+276G/T单核苷酸多态性与冠心病的相关性研究

目的探讨上海汉族人群中脂联素基因多态性分布情况，研究基因多态性与冠心病的相关性。方法采用聚合酶链反应-限制性片段长度多态性（PCR—RFLP）方法，以100例健康者为对照组，100例冠脉造影证实为冠心病的非糖尿病患者为冠心病组，研究脂联素基因单核苷酸多态性（SNP276G／T）与冠心病的相关性。结果冠心病组G／G基因型频率明显高于对照组，分别为29％和16％（P〈0．05），冠心病组G等位基因频率为45％，对照组为16％，冠心病组明显高于对照组（P〈0．05）；T等位基因频率冠心病组明显低于正常对照组，分别为55％和84％（P〈0．05）。相对于T／T基因型，G／G基因型修正后的OR值为3．93（P〈0．05），G／G＋G／T基因型的修正后的OR值为2．41。结论脂联素SNP＋276G／T各种基因型和冠心病的发病密切相关，G／G基因型很可能是冠心病的易感基因型。     

雌激素受体α和维生素D受体基因多态性与上海市妇女峰值骨量的关系

目的　探讨上海市妇女雌激素受体α(ER α)基因和维生素D受体 (VDR)基因多态性与峰值骨量的关系。方法　对上海市 5 15例无亲缘关系 19～ 40岁汉族健康妇女进行PCR RFLP测定ER α基因PvuⅡ、XbaⅠ多态性和VDR基因ApaⅠ多态性 ,用双能X线吸收法测定骨密度 (BMD)。 结果　本研究人群PP、Pp及pp基因型频率分别为 13 .2 %、49.3 %、3 7.5 % ;XX、Xx及xx基因型频率各为 4.7%、40 .4%、5 4.9% ;AA、Aa及aa基因型频率分别为 5 .8%、41.9%、5 2 .3 %。以上等位基因频率分布均符合Hardy Weinberg定律。协方差方法分析各基因型与BMD值的关系显示 :仅VDR基因ApaⅠ多态性与妇女L1 4BMD值显著相关 (P <0 .0 5 ) ,AA基因型在L1 4BMD值均低于Aa/aa基因型 ,差异有显著性 (P <0 .0 5 )。结论　ER α基因PvuⅡ和XbaⅠ多态性对上海市妇女峰值骨量无潜在影响 ;VDR基因ApaⅠ多态性与上海市妇女腰椎峰值骨量的达到和维持有关 ,而且独立于ER α基因PvuⅡ和XbaⅠ多态性。     

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.     

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.     

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.     

Serological survey of HIV and syphilis in pregnant women in Madagascar

Objectives Peripartal transmission of human immunodeficiency virus (HIV) and Treponema pallidum, the causative agent of syphilis, leads to severe consequences for newborns. Preventive measures require awareness of the maternal infection. Although HIV and syphilis testing in Madagascar could be theoretically carried out within the framework of the national pregnancy follow‐up scheme, the required test kits are rarely available at peripheral health centres. In this study, we screened blood samples of pregnant Madagascan women for HIV and syphilis seroprevalence to estimate the demand for systemic screening in pregnancy. Methods Retrospective anonymous serological analysis for HIV and syphilis was performed in plasma samples from 1232 pregnant women that were taken between May and July 2010 in Ambositra, Ifanadiana, Manakara, Mananjary, Moramanga and Tsiroanomandidy (Madagascar) during pregnancy follow‐up. Screening was based on Treponema pallidum haemagglutination tests for syphilis and rapid tests for HIV, with confirmation of positive screening results on line assays. Results Out of 1232 pregnant women, none were seropositive for HIV and 37 (3%) were seropositive for Treponema pallidum. Conclusions Our findings are in line with previous studies that describe considerable syphilis prevalence in the rural Madagascan population. The results suggest a need for screening to prevent peripartal Treponema pallidum transmission, while HIV is still rare. If they are known, Treponema pallidum infections can be easily, safely and inexpensively treated even in pregnancy to reduce the risk of transmission.     

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.