GLI1基因内2个SNP位点与单纯性先天性心脏病的关联研究

目的在前期工作定位的单纯性先天性心脏病(CHD)易感区域12q13内,选取GLI1基因编码区内2个已知单核苷酸多态(SNP):rs11553626和rs2228226,检测其在单纯性CHD患者和正常人群中的分布情况,分析其与单纯性CHD的相关性。方法对2000年1月至2005年6月于中国医科大学第一临床学院和沈阳军区总医院收集的180例单纯性CHD患者及200名正常人,应用变性高效液相色谱(DHPLC)结合测序分析2个SNP位点基因型,应用χ2检验统计分析CHD组和对照组各SNP位点基因型频率及等位基因频率。结果rs11553626位点未检测到多态;rs2228226位点存在G/C多态,CHD组和对照组等位基因频率分布(χ2=8·956,P<0·005)及基因型频率分布(χ2=11·286,P<0·005)差异显著,CHD组G等位基因频率及GG、GC基因型频率增高,CC基因型频率降低。结论GLI1基因编码区SNP位点rs11553626在中国东北人群中可能不存在多态性;rs2228226位点与单纯性CHD有明显的相关性,具有G等位基因的人发生CHD的危险性相对增高。     

新疆维吾尔族人群9p21单核苷酸多态性与冠心病的关联性研究

目的研究染色体9p21上两个单核苷酸多态性（single nucleotide polymorphism,SNP）位点（rs2383206、rs10757274）在新疆维吾尔族人群中的分布,探讨其与冠心病（coronary heart disease,CHD）的关联性。方法采用病例对照研究,选择172例冠状动脉造影证实的CHD患者和147例患者为对照组作为研究对象,应用LDR—PCR技术对rs2383206、rsl0757274位点进行SNP分型及分析。结果rs2383206GG基因型频率在冠心病组和对照组分别为34．9％和24．4％,G等位基因频率分别为58．1％和49．3％;两组间比较差异均有统计学意义（P〈0．05）;rsl0757274GG基因型频率在冠心病组和对照组分别为32．O％和21．8％,G等位基因频率分别为54．9％和46．6％;两组间比较差异均有统计学意义（P〈0．05）。调整相关因素后,多因素Logistic回归分析,结果提示两个SNP的GG基因型仍是CHD的危险基因型,rs2383206的OR值为1．91,95％CI（1．03～3．53）,rsl0757274的OR值为2．03,95％CI（1．08～3．80）,P值均〈0．05。结论9p21位点rs2383206、rsl0757274的多态性与维吾尔族族人CHD有关联。     

染色体9p21上两个SNP位点与中国汉族人群心肌梗死的关系

目的研究染色体9p21上两个单核苷酸多态性（SNP）位点（rs10757274、rs2383206）在中国汉族人群中的分布,探讨其与心肌梗死（MI）的相关性。方法选择432例初发MI（MI组）及430例外科疾病（对照组）患者,用PCR-SNP Stream技术对rs10757274、rs2383206位点进行SNP分型及分析。结果MI组两个SNP位点的GG、AG基因型分布及G等位基因频率均高于对照组（P均〈0.01）。校正混杂因素后显示,两个SNP位点中的G等位基因可使MI患病风险分别提高44%和54%（P〈0.01）。结论rs10757274、rs2383206是中国汉族人群MI发生的易感位点。     

高血压定位区域犬尿氨酸酶基因多态性与高血压病相关

目的检测中国汉族人群高血压病定位区域2q14-q23内犬尿氨酸酶基因（kynureninase,KYNU）调控区和编码区的单核苷酸多态性（single nucleotide polymorphism,SNP）及与高血压病的相关性。方法采用直接测序法检测KYNU基因启动子区和外显子序列中的SNP。应用变性高效液相色谱分析（DHPLC）技术对位于编码区且改变氨基酸编码的Lys412Glu（A／G）多态在456例高血压病患者和430例正常对照者中进行分型和关联研究。结果共检测得KYNU基因的16个SNP,其中启动子区6个,编码区2个（均改变氨基酸编码）。Lys412Glu多态基因型分布（x^2 = 6．693,P =0．035）和等位基因频率分布（x^2 = 4．188,P = 0．041）在高血压病组和正常对照组间差异均有统计学意义,Lys412Glu等位基因频率分布在男性高血压病组和正常对照组间差异有统计学意义（x^2 = 4．424,P = 0．035）。结论中国汉族高血压病定位区域内KYNU基因Lys412Glu多态可能与高血压病相关。     

色素上皮衍生因子启动子区基因多态性与糖尿病微血管病变的关系

目的观察色素上皮衍生因子（PEDF）启动子区单核苷酸多态性（SNP）与糖尿病微血管病变的关系。方法将271例T2DM患者分为无糖尿病微血管病变组105例,合并糖尿病微血管并发症组166例,分析PEDF基因启动子区rs12150053T／C及rs12948385G／A的基因型和等位基因频率。结果两个SNPs位点等位基因频率均有统计学差异（P〈0．05）,rs12948385位点基因型频率也有统计学差异（P〈0．05）。结论PEDF启动子区多态性位点可能是我国北方汉族人群糖尿病微血管病变发病的危险因素之一。     

TBX1基因与人类圆锥动脉干畸形相关性的研究

目的在TBX1基因内选取2个已知单核苷酸多态(SNP)G2857C(rs737868)和G2963A(rs28649236),检测其在圆锥动脉干畸形患者和正常人群中的表达情况,分析TBX1基因与圆锥动脉干畸形的相关性。方法2004年3月至2006年5月沈阳军区总医院应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法分析100例圆锥动脉干畸形患者及100名正常人2个SNP位点基因型;应用列联表法统计分析病例组和对照组各SNP位点基因型及等位基因频率。结果G2963A位点等位基因频率及基因型频率在病例组和对照组中的分布差异有显著性,病例组G等位基因频率明显高于对照组(χ2=5.30,P<0.05)。结论TBX1基因编码区的SNP位点G2963A与人类圆锥动脉干畸形有明显的相关性,具有G等位基因的人发生圆锥动脉干畸形的危险性相对增高。     

中国人群COL1A2基因多态性与散发颅内动脉瘤的相关性

目的探讨Ⅰ型胶原蛋白基因α2（COL1A2）与中国人群颅内动脉瘤（IA）发生之间的关系及中国与日本、德国人群COL1A2等位基因频率分布特征。方法研究实验组与对照组之间COL1A2基因功能性SNPrs42524位点的基因型和等位基因出现的频率差异,同时对中国人群与日本和德国人群进行组间等位基因出现的频率差异性比较。结果实验组和对照组COL1A2基因功能性SNP rs42524位点基因型频率及等位基因频率均有统计学差异（P〈0．05）;不同人群之间COL1A2等位基因频率也具有统计学差异（P〈0．01）。结论COL1A2基因是中国人群IA患者的易感基因之一,中国人群与日本、德国人群COL1A2等位基因分布均具有显著性差异。     

胆固醇酯转运蛋白基因6个多态位点与冠心病的关系

目的:了解胆固醇酯转运蛋白(CETP)基因TaqIB等6种突变的多态性与海南汉族冠心病(CHD)的关系.方法:应用针对CETP基因TaqIB、I405V、D442G、R451Q、A373P和I14A多态位点设计的等位基因特异性PCR技术,对301例海南汉族正常对照组、334例海南汉族CHD患者中CETP基因多态位点进行了检测,统计各基因型频率,计算各等位基因频率.结果:①正常对照组和CHD组中,TaqIB多态位点均可检测出B_1B_1、B_1B_2、B_2B_2 3种基因型.正常对照组B_1B_1、B_1B_2、B_2B_2 3种基因型的频率分布为45.18%、39.87%、14.95%,B_1和B_2的等位基因频率分布为65.12%、34.88%;CHD组B_1B_1、B_1B_2、B_2B_2 3种基因型的频率分布为51.50%、31.74%、16.77%,B_1和B_2的等位基因频率分布为67.37%、32.63%.②I405V突变位点可检测出Ⅱ、Ⅳ、VV 3种基因型.正常对照组Ⅱ、Ⅳ、VV 3种基因型的频率分布为15.95%、48.50%、35.55%,Ⅰ和Ⅴ的等位基因频率分布为40.20%、59.80%; CHD组Ⅱ、Ⅳ、VV 3种基因型的频率分布为15.27%、35.33%、49.40%,Ⅰ和Ⅴ的等位基因频率分布为32.93%、67.07%.③D442G突变位点可检测出DD、DG 2种基因型.正常对照组DD、DG 2种基因型的频率分布为95.35%、4.65%,D和G的等位基因频率分布为97.67%、2.33%;CHD组DD、DG 2种基因型的频率分布为63.47%、36.53%,D和G的等位基因频率分布为81.74%、18.26%.④正常对照组和CHD组中均未检测到R451Q、A373P和I14A 3种突变类型.⑤正常对照组与CHD组I405V和D442G 2个多态位点的基因型分布和等位基因频率的比较差异有统计学意义,其余多态位点在正常对照组与CHD组之间差异均无统计学意义.结论:I405V和D442G的多态性与海南汉族CHD显著相关.I405V多态位点V等位基因、D442G多态位点G等位基因是海南汉族CHD的易感基因,而I405V多态位点I等位基因对其有保护作用.D442G多态位点DG基因型可使海南汉族人群CHD的发病危险性显著增加.     

OCTN1/OCTN2基因多态性与中国汉族人群炎症性肠病相关性的初步研究

近年研究证实OCTN1/OCTN2基因单核苷酸多态性（SNP）与西方白种人群克罗恩病（CD）明显相关,其中OCTN1基因rs1050152位点和OCTN2基因rs2631367位点SNP与CD的相关性尤为显著.目的：初步探讨OCTN1基因rs1050152位点和OCTN2基因rs2631367位点基因多态性与中国汉族人群炎症性肠病（IBD）的相关性.方法：KR联合直接测序法检测45例CD患者、45例溃疡性结肠炎（UC）患者和50名正常对照者OCTN1基因rs1050152位点和OCTN2基因rs2631367位点的基因型,比较各组基因型和等位基因频率.结果：CD,UC和正常对照组间OCTN1基因rs1050152位点基因型和等位基因频率差异均无统计学意义（R〉0.05）;三组OCTN2基因rs2631367位点均未发现突变基因型.结论：OCTN1基因rs1050152位点和OCTN2基因rs2631367位点基因多态性与中国汉族人群IBD不相关.     

脑源性神经营养因子基因Val66Met多态性与阿尔茨海默病的相关性

目的 探讨中国汉族人群中脑源性神经营养因子（BDNF）基因Va166Met单核苷酸多态性（SNP）与阿尔茨海默病（AD）的相互关系。方法 采用等位基因特异性聚合酶链反应（A—SPCR）技术检测513例AD患者和575例健康老年人BDNF基因Va166Met位点SNP的分布，分析各基因型与发病年龄和疾病严重程度的关系。结果 AD组和对照组基因型频率（22．0％和21．7％；x^2=0．41，P=0．82）、等位基因频率（45．9％和46．5％；x^2=0．08，P=0．77）差异均无统计学意义（P〉0．05）。进一步将AD组按照发病年龄（〈65岁和≥65岁）和性别分层，也未发现差异有统计学意义（P〉0．05）。各基因型与发病年龄和疾病的严重程度不存在相关性。结论 中国汉族人群中BDNF基因Va166Met位点SNP与AD未发现关联关系。     

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.     

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.     

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.