肥胖哮喘病人瘦素基因G-2548A位点多态性及水平变化

目的探讨瘦素基因启动子区G-2548A位点多态性和血清瘦素水平变化与肥胖哮喘之间的关系。方法从本实验室哮喘文库中选择研究对象,分为肥胖哮喘、正常体重哮喘、肥胖对照和健康对照四组。根据病情严重程度将正常体重哮喘组分为轻度和中重度持续2个亚组。采用聚合酶链反应-限制性片段长度多态性分析方法测定瘦素基因启动子区G-2548A位点多态性,ELISA法测定瘦素、IL-6及TNF-α水平。同时测定受试者的肺功能。结果 (1)肥胖哮喘和肥胖对照组瘦素基因G-2548A位点AA基因型频率及A等位基因频率与正常对照组比较有显著性差异(χ2=4.167~6.095,P0.05);(2)正常体重哮喘组中的中重度持续亚组AA基因型频率及A等位基因频率与正常对照组比较有显著性差异(χ2=4.080、3.716,P0.05);(3)哮喘组AA基因型与GA+GG基因型组比较,瘦素、IL-6、TNF-α、CRP水平明显升高(P0.01),FEV1%和FEV1/FVC%明显下降(P0.01)。结论瘦素基因启动子区G-2548A位点A等位基因可能是肥胖和哮喘共同的遗传易感因素,瘦素可能是肥胖-哮喘关联路径中的一个重要细胞因子,通过影响其他炎性因子水平变化而在肥胖哮喘的发病机制中发挥重要作用。     

血管紧张素原基因G-6A多态性与冠心病的相关性研究

目的 探讨我国河南汉族人群血管紧张素原基因核心启动子区域G-6A多态性与冠心病(CHD)的关系.方法 选择504例确诊CHD的患者和512例无心脏病史的健康体检者,运用多聚酶链反应一限制性内切酶片段长度多态性技术(PCR-RFLP)进行G-6A多态性检测.结果 CHD组A/A基因型频率是64.9%,高于对照组的54.9%(X<'2>=10.565,P<0.05);CHD组A等位基因频率是81.4%,高于对照组的73.3%(X<'2>=19.071,P<0.05).结论 血管紧张素原基因G-6A多态性中A/A纯合子与CHD的发生之间存在相关性,其中A等位基因可能是CHD发病的遗传危险因子.     

瘦素基因2548G/A多态性与阻塞性睡眠呼吸暂停低通气综合征易感性的关系探讨

目的探讨瘦素基因2548G/A基因多态性与阻塞性睡眠呼吸暂停低通气综合征(OSAHS)易感性的关系。方法采用聚合酶链反应—限制性片段长度多态性(PCR-RFLP)方法检测90例肥胖OSAHS患者(A组)、93例非肥胖OSAHS患者(B组)、105例单纯肥胖者(B组)及96例健康人(D组)瘦素基因2548G/A的基因型并计算等位基因频率,分析其与OSAHS易感性的关系。结果各组基因型及等位基因比较均无统计学差异(P均>0.05);在OSAHS患者中,AA基因型患者腰臀比明显低于AG型和GG型(P均<0.05),余指标比较均无统计学差异(P均>0.05)。结论瘦素基因2548G/A多态性与OSAHS的发病无关,但2548G/A变异可能与腹型肥胖的发生有关。     

MMP-9基因启动子C1562T多态性与老年冠心病易感性的相关性研究

目的探讨基质金属蛋白酶9(MMP-9)基因启动子C1562T多态性与老年冠心病(CHD)易感性的相关性。方法纳入2009年3月~2012年12月北京航天总医院年龄≥60岁的CHD患者168例作为CHD组,纳入同期健康体检者208例作为对照组。取外周血标本提取DNA,采用聚合酶链式反应-限制性内切酶片段长度多态性(PCR-RFLP)方法检测MMP-9基因启动子C1562T基因型,比较两组间MMP-9基因多态性频率分布的差异。结果 MMP-9基因启动子区C1562T多态性基因型和等位基因频率分布在CHD组和对照组之间差异有统计学意义(P0.05)。CHD组1562T等位基因频率明显高于对照组(20.8%vs.13.0%,P=0.004),携带T等位基因个体患冠心病的风险是C等位基因的3.97倍(OR=3.97)。不同临床类型的CHD患者在基因型及等位基因分布方面的差异无统计学意义(P0.05)。结论 MMP-9基因C1562T多态性与老年CHD的发生有关联,T等位基因可能是冠心病发病的遗传易感基因。     

肿瘤坏死因子-α基因多态性与急性冠脉综合征发病关系的研究

目的:探讨肿瘤坏死因子-α(TNF-α)基因启动子区域的G-238A和G-308A多态对急性冠脉综合征发病的影响。方法:利用DNA直接测序法,入选急性冠脉综合征患者(ACS组)70例及汉族正常对照组64例,对TNF-α基因启动子区域的G-238A和G-308A多态位点分别进行检测。结果:在ACS组中,TNF-α基因启动子区域G-308A多态的基因型分布(GG=31、GA=9、AA=30)及其等位基因频率(G=50.71%、A=49.29%)与正常对照组(GG=47、GA=4、AA=13;76.56%、23.44%)相比均有显著性差异(P<0.01);G-238A多态的基因型分布(GG=44、GA=8、AA=18)与正常对照组(GG=55、GA=2、AA=7)相比,统计学上有显著性差异(P<0.01),等位基因频率(G=68.57%、A=41.43%)与正常对照组(G=87.50%、A=12.50%)相比也有显著差异(P<0.01)。结论:TNF-α基因启动子区域G-238A和G-308A多态可能与急性冠脉综合征的发生相关,TNF-α基因变异可能是急性冠脉综合征的重要遗传危险因素。     

瘦素基因启动子区C2549A多态性与肝硬化的关系

目的了解中国人瘦素基因启动子的基因型分布,探讨瘦素基因多态性与血浆瘦素水平及肝硬化患者临床表型间的关系。方法应用聚合酶链反应及限制性片段长度多态性方法(PCR-RFLP)对78例肝硬化患者和82例对照组的瘦素基因启动子2549位核苷酸变异(C2549A)进行研究,同时进行血浆瘦素水平和临床参数的检测。结果1.肝硬化患者和对照组人群中C2549A基因型频率和等位基因频率比较差异无显著性(P>0.05);2.肝硬化患者中AA AC基因型携带者空腹血浆瘦素较CC型降低(P<0.05),女性中AA AC基因型携带者空腹血浆胰岛素、胰岛素抵抗指数水平低于CC基因型携带者(P<0.05);3.进一步用Logistic回归分析发现,瘦素基因C2549A变异与男性肝硬化患者的胰岛素抵抗指数(HOMA-IR)相关(P=0.026),女性肝硬化患者与空腹胰岛素(P=0.0005)及胰岛素抵抗指数(P=0.0043)相关。结论肝硬化患者瘦素基因C2549A多态性与空腹血浆瘦素水平相关。     

黏附分子E-选择素A128C基因多态性与冠心病的关系

目的研究中国汉族人群黏附分子E-选择素（E-selectin）基因外显子4,128编码处碱基A/C多态性与冠心病（CHD）的相关关系,探讨通过黏附分子E-selectin基因型筛选CHD易患人群和高危人群的可能性。方法入选145例CHD患者,其中73例为急性冠脉综合征（ACS）,72例为稳定型冠心病（SCHD）,并入选144例为对照组。所有CHD患者均经冠状动脉造影证实。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术,分析E-选择素基因型。结果与对照组相比,ACS患者和SCHD患者的E-选择素基因型频率和等位基因频率差异均有显著性。基因型频率的相对风险分析发现,CC+AC基因型患冠心病的风险是AA基因型的5.843倍（OR=5.843,95%C I:3.066-11.133）。结论E-选择素基因A/C多态性与CHD相关,C等位基因可能是CHD发病的遗传易感基因。     

Klotho基因G-395A多态性与动脉硬化的相关性研究

目的研究重庆市汉族人群Klotho基因启动子区域G-395A单核苷酸多态性的分布,探讨该多态性位点与动脉硬化的相关性。方法232例健康体检者均进行臂踝脉搏波传导速度测定,并记录动脉硬化的传统危险因素,根据测定结果分为动脉硬化组(130例)和对照组(102例)。应用TaqMan探针等位基因特异性杂交分析法对Klotho基因G-395A多态性位点进行分析。结果G-395A多态性位点共检测出GG、GA、AA3种基因型,频率分别为60.3%、34.1%和5.6%,符合Hardy-Weinberg平衡。动脉硬化组-395A等位基因的频率显著低于对照组(33.1%vs48.0%,P=0.022)。logistic回归分析,调整传统危险因素后-395A与动脉硬化呈负相关(P=0.042,OR=0.537,95%CI:0.295~0.977)。结论Klotho基因-395A等位基因可能是动脉硬化的遗传学保护因素。     

乙醛脱氢酶2基因多态性与老年冠心病的相关性

目的探讨乙醛脱氢酶2(ALDH2)基因G487A多态性与老年冠状动脉粥样硬化性心病(CHD)患者的关系。方法 320例行冠状动脉造影的老年患者,根据造影结果分为CHD组169例和非CHD组(对照组)151例,利用多聚酶链反应技术,检测ALDH2基因G487A多态性。结果基因型频率符合Hardy-Weinberg平衡;CHD组AA+AG基因型(ALDH2*2/*2+ALDH2*1/*2)频率明显高于GG型(ALDH2*1/*1)组,与对照组有显著性差异(P=0.011);Logistic回归分析显示,A等位基因、低HDL-C增加了CHD的危险,A等位基因、低HDL-C对CHD的发生有协同作用。结论 ALDH2基因G487A多态性与老年冠心病的发病有关,A等位基因可能是CHD发病的遗传危险因素之一。     

载脂蛋白M基因rs707921位点多态性与冠心病易感性的关系

目的检测载脂蛋白M(ApoM)基因rs707921位点的基因多态性,探讨其与冠心病(CHD)的相关性。方法采用单荧光标记探针技术检测111例CHD患者及248例对照组的ApoM rs707921位点单核苷酸多态性,分析其基因型和等位基因频率的分布情况。结果 ApoM rs707921位点3种基因型(AA型、AC型和CC型)在CHD组中分布频率为1.8%、13.5%和84.7%,在对照组中分布频率为2.0%、25.4%和72.6%,两组差异有统计学意义(P=0.039);ApoM rs707921位点A、C等位基因的频率在CHD组和对照组中分布频率分别为8.6%、91.4%和14.7%、85.3%,两组比较差异有统计学意义(P=0.023)。CHD组中AC+AA基因型者甘油三酯水平显著低于CC基因型者(P=0.043)。CHD组rs707921位点多态性不同基因型间冠状动脉病变严重程度差异无统计学意义(P0.05)。结论ApoM基因rs707921位点A等位基因可能降低CHD的发病风险,但与CHD的严重程度无关。     

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.     

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.     

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.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.