金属硫蛋白基因多态性与昆明地区汉族2型糖尿病的相关性研究

目的 探讨金属硫蛋白(MT)1A基因rs8052394多态性与昆明地区汉族T2DM的相关性。方法 采用Taqman实时荧光定量PCR技术对257例T2DM患者(T2DM组)和108名健康对照(NC)组MT1A基因型进行检测。结果 T2DM组MT1A基因rs8052394A/A基因型频率及A等位基因频率高于NC组(χ~2=20.519、29.213,P0.01)。Logistic回归分析显示,MT1A rs8052394A/A基因型携带者相对于A/G和G/G基因型携带者患T2DM的危险性增加。结论 昆明地区汉族人群MT1A基因rs8052394多态性可能与T2DM的发生有关,A等位基因可能增加T2DM的发病风险。     

抵抗素+299G/A基因多态性与2型糖尿病并大血管病变的相关性研究

目的 研究抵抗素基因+299G/A多态性与中国北方地区汉族中老年人群2型糖尿病(T2DM)并大血管病变的关系.方法 应用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)检测汉族人群296例抵抗素基因内含子2区299G/A的突变.结果 与对照组相比,糖尿病组等位基因频率、基因型分布差异显著(P=0.012,P=0.025).糖尿病组A等位基因突变率明显低于对照组,并大血管病变发生率在三种基因型间差异不显著(P=0.149).A,B两组等位基因频率、基因型分布的比较均无显著性.B组G/A基因型亚组的FPG显著高于A/A基因型亚组(P=0.05);利用Logistic回归分析显示收缩压、舒张压、低密度脂蛋白胆固醇(LDL-C)、家族史是糖尿病大血管病变的独立危险因素.结论 抵抗素基因+299G/A多态性与T2DM有关,A等位基因可能是T2DM的微效保护因素;AA基因型者在糖尿病并大血管病变组中有较低的FPG.     

吉林汉族人群糖尿病与维生素D受体基因的相关性

目的通过测定吉林地区2型糖尿病(T2DM)患者维生素D受体(VDR) Bsm1位点基因型和等位基因频率,探讨VDR Bsm1位点基因多态性与T2DM的相关性。方法选取吉林地区T2DM患者150例纳入T2DM组,通过聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)检测T2DM患者VDR Bsm1位点基因型和等位基因频率,根据VDR Bsm1位点基因是否携带B等位基因型分为BB+Bb组和bb组。同期收集健康体检者100例纳入正常对照组,所有研究对象分别测定如下指标:空腹血糖(FPG)、餐后2 h血糖(2 hPG)、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、糖化血红蛋白(HbA1c)。结果 T2DM组中BB+Bb基因型明显高于正常对照组(37.33%vs 12.0%,P0.05),B等位基因频率明显高于正常对照组(19.34%vs 7.0%,P0.05),基因型bb明显低于正常对照组(62.67%vs 88.0%,P0.05),差异均具有统计学意义。结论 VDR Bsm1位点多态性与中国吉林地区汉族人群T2DM密切相关,可能是该地区人群T2DM的一个易感基因。     

ACE基因、AT1R基因多态性与2型糖尿病肾病的关系

目的研究血管紧张素I转化酶(ACE)基因/D多态及血管紧张素受体1型(AT1R)A1166C多态性与中国汉族人2型糖尿病肾病(DN)的关系。方法运用聚合酶链反应(PCR)和PCR/DdeI酶切技术,检测93例DN患者(DN组)与94例2型糖尿病患者(DM组)ACE基因及AT1R基因多态基因型。结果DN组ACE基因DD基因型频率(34.4%)、D型等位基因频率(54.3%)较DM组(19.1%,40.4%)均升高(P<0.05,<0.01);两组间AT1R基因A1166C多态基因型频率和等位基因频率分布均无差异(P>0.05);ACE和AT1R基因多态与DN的分层分析显示,同时携带ACE纯合子缺失基因型(DD)和AT1R突变基因型(AC+CC)者发生DN的危险较大,OR值为8.569。结论ACE基因/D多态性与2型DM并发DN有关,携带DD基因型和D型等位基因的2型DM患者是DN的易感人群。ATlR基因A1166C多态性虽与我国汉族人2型DM并发DN无关,但AT1R与ACE基因多态存在协同效应,携带AC+CC与DD基因型的个体有更高的患DN风险。     

脂联素受体1基因多态性与2型糖尿病相关性研究

目的研究西安地区汉族人群中脂联素受体1（AdipoR1）的两个单核苷酸多态性（SNP）位点与2型糖尿病（T2DM）的关系。方法采用突变特异性扩增系统（ARMS）结合测序方法对西安地区100例T2DM患者（T2DM组）及84名正常对照者（NC组）AdipoRl基因的两个SNP位点进行分析。结果（1）AdipoR1基因SNP-106A／G、SNP 5843A／G在DM组与NC组间基因型频率及等位基因频率差异无统计学意义。（2）AdipoR1基因5843G／G型T2DM患者的诊断年龄明显早于A／A型＋A／G型。结论在西安地区的汉族人群中，AdipoR1基因-106A／G、5843A／G的单个核苷酸多态性可能与T2DM的发病无关。携带5843G／G基因型的T2DM患者发病年龄较早。     

糖尿病微血管病SUMO基因163 A/G多态性的相关性研究

目的:探讨小泛素样修饰蛋白(SUMO)基因163A/G多态性与糖尿病微血管病变相关性。方法:运用聚合酶链反应-限制性片段长度多态性方法,对30例2型糖尿病(T2DM)患者[正常白蛋白尿(DM0)组10例,微量白蛋白尿(DM1)组10例,大量白蛋白尿(DM2)组10例]和10例健康对照者(NC)的SUMO基因163A/G多态性进行检测,并比较各组间基因型频率、等位基因频率及相关临床指标。结果:本组实验人群中SUMO基因163位点存在3种基因型,即AA型、GA型和GG型。NC组与T2DM组各基因型和等位基因频率无显著差异(x2=2.231,P=0.121;x2=0.015,P=0.906);DM组(DM1+DM2)的GA基因型频率高于DM0组(x2=4.454,P=0.038);DM1组与DM2组基因型和等位基因频率无统计学差异(x2=0.041,P=0.973;x2=0.123,P=0.683)。Logistic回归分析显示SUMO基因GA基因型(OR=2.31,P0.05)与糖尿病肾病相关。结论:SUMO基因GA基因型可能是糖尿病微血管病发生的危险因素。     

脂蛋白脂酶基因Hind Ⅲ和Pvu Ⅱ酶切多态性与异常体液型2型糖尿病的相关性

目的 探讨脂蛋白脂酶(LPL)基因HindⅢ和PvuⅡ酶切多态性与新疆维吾尔自治区汉族人群异常体液型2型糖尿病(T2DM)的关系.方法 按维吾尔医学将T2DM患者分为4种体液型,应用PCR-RFLP技术分析87例T2DM患者和157例正常人LPL基因HindⅢ和PvuⅡ酶切位点的基因型.结果 异常黏液质型和异常黑胆质型T2DM组H-等位基因、H+H-基因型和P-P-基因型的频率较对照组显著增高(H-:37.5％比18.5％,39.7％比18.5％,P＜0.05;H+H-:55.0％比29.3％,58.6％比29.3％,P＜0.05;P-P-:35.0％比10.8％,27.6％比10.8％,P＜0.05).在异常黏液质型和异常黑胆质型T2DM组中携带突变[(H+H-)+(H+H)]基因型的个体较携带H-H-基因型的个体患T2DM的危险性增加(OR=2.793,95％ CI为0.525～ 14.925;OR=2.907,95％ CI为0.683～12.345),在这两组中携带突变[(P+P-)+(P+P+)]基因型的个体较携带P-P-基因型的个体患T2DM的危险性增加(OR=4.425,95％ CI为1.555～ 12.658;OR=3.134,95％ CI为1.205～8.197).结论 LPL基因HindⅢ和PvuⅡ多态性与新疆汉族人异常黏液质型和异常黑胆质型T2DM的危险性相关,与新疆汉族人异常胆液质型和异常血液质型T2DM的危险性无关.     

乙酰辅酶A羧化酶B基因rs2268388多态性与糖尿病慢性肾脏疾病的相关性研究

目的 探讨乙酰辅酶A羧化酶B(ACACB)基因rs2268388多态性与我国昆明地区汉族人群糖尿病慢性肾脏疾病(CKD)的相关性. 方法 选取T2DM患者248例,根据两次UAlb/Cr或24 hUAlb结果分为单纯T2DM组85例、CKD1组99例及CKD2组64例,另选取健康对照(NC)组70名.采用Taqman PCR(Three-star)法对各组ACACB基因rs2268388多态性进行检测,并比较分析各组基因型、等位基因频率、风险因素及相关临床和生化指标. 结果 (1)单纯T2DM、CKD各组C/T基因型频率均低于NC组(Z=-2.391,P=0.017);CKD1组和CKD2组ACACB基因rs2268388T/T基因型频率高于单纯T2DM组(Z=-2.522,P=0.012;Z=-4.981,P=0.001);CK D1组和CKD2组T/T基因型频率及各组等位基因频率比较,差异无统计学意义(P＞0.05).(2) Logistic回归分析表明,糖尿病病程、rs2268388T/T基因型、高TG、高HbA1 c及高SUA是CKD发生的危险因素. 结论 在昆明地区汉族人群中,ACACB基因rs2268388T/T基因型可能与CKD发生相关.     

甘露聚糖结合凝集素基因A/B位点与新疆维吾尔族结核病的相关性研究

目的 探讨甘露聚糖结合凝集素（mannan-binding lectin,MBL）基因的多态性是否与新疆维吾尔族人群结核病发病相关。 方法 通过使用引物序列特异性PCR(SSP-PCR)的方法分别对226例新疆维吾尔族活动性肺结核患者（简称病例组）及231例有结核分枝杆菌接触史的新疆同民族健康者（简称对照组）进行MBL基因的A/B多态性位点进行基因分型,统计学分析采用病例对照分析研究不同基因型与新疆维吾尔族结核病易感性的关系。 结果 在病例组中,MBL基因A/B位点 AA 基因型106例(占46.90%),AB基因型106例（占46.90%),BB基因型14例(占6.20%);对照组AA基因型则为146例(占63.20%),AB基因型80例(占34.63%),BB基因型5例(占2.17%)。病例组中MBL-AB突变基因频率显著高于健康对照组,两组的突变基因频率分别为6.20%、2.17%,差异有统计学意义(χ²=5.224,P_c＜0.05)。 结论 新疆维吾尔族人群中MBL基因AA基因型可能为结核病的保护性因素,BB基因型可能为结核病发病的危险性因素。新疆维吾尔族人群中MBL基因A/B位点多态性与结核病易感性有明显相关性。     

1型糖尿病患者人类白细胞抗原Ⅰ类基因与胰岛功能及胰岛自身抗体的关系

目的 探讨1型糖尿病（T1DM）患者胰岛功能、胰岛自身抗体[谷氨酸脱羧酶抗体（GADA）、蛋白酪氨酸磷酸酶抗体（IA-2A）、胰岛素自身抗体（IAA）和阳离子外流锌转运体蛋白抗体（ZnT8A）]与人类白细胞抗原（HLA）Ⅰ类等位基因的关系.方法 选取2008年6月至2012年10月在南京医科大学第一附属医院及其开放课题26家医院（共同组成江苏省T1DM合作组）内分泌科就诊的T1DM患者330例.采用聚合酶链反应-寡核苷酸探针序列特异性引物（PCR-SSO）技术进行T1DM患者HLAⅠ类基因（A、B基因）分型,放射免疫配体法检测胰岛自身抗体（GADA、ZnT8A、IA-2A、IAA）.选择同地区、遗传背景相近的中华骨髓库无关供者HLA分型资料20 248份作为研究对照.通过Arlequin软件进行HL4Ⅰ类等位基因频率及单倍型频率分析.定量资料的组间比较采用独立样本的t检验.结果 与对照组相比,T1DM组HLA-A＊24、B＊08、B＊41、B＊54、B＊58频率明显升高（OR=1.250、2.062、6.927、2.472、1.608,均P＜0.05）;A＊01、B＊07、B＊27、B＊52、B＊57频率显著下降（OR =0.481、0.464、0.372、0.160、0.315,均P＜0.05）;HLA-A＊24-B＊ 54单倍型频率明显升高（OR=4.128,P＜0.05）.携带A＊02基因位点的T1DM患者其空腹C肽水平高于不携带A ＊02的患者[（356±249）比（250±199） pmol/L,t=-3.004,P＜O.05].未发现HLAⅠ类基因与胰岛自身抗体存在统计学关联.结论 江苏地区汉族T1DM患者中,HLAⅠ类等位基因不仅可影响T1DM的发病风险,而且可能影响发病后胰岛功能的衰竭速度.     

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.