2型糖尿病血管并发症患者细胞间黏附分子-1基因多态性研究

目的研究细胞间黏附分子-1（ICAM-1）469K〉E基因多态性位点等位基因分布频率及其与2型糖尿病（T2DM）血管病变的关系。方法采用聚合酶链式反应（PCR）方法检测62例T2DM血管并发症患者ICAM-1469KK、KE及EE基因型出现的频率。并检测其空腹血糖（BS）、甘油三酯（TG）、糖化血红蛋白（HbAIc）、血浆游离ICAM-1（sICAM-1）和总胆固醇（TC）水平，并与70例无血管并发症的T2DM患者及121例正常对照组比较。结果KK、KE、EE3种基因型在3组中的分布频率有明显差异（，=6．313，P=0．043）．DM血管病变组等位基因E的频率明显高于对照组和无血管病变组（P〈0．01），T2DM血管病变组ICAM-1469E等位基因携带者sICAM-1水平明显高于K等位基因携带者（P〈0．01）。结论ICAM—1469E等位基因与DM血管病变及ICAM-1水平升高有关。     

三基因单核苷酸多态性与汉族人群2型糖尿病的相关性研究

目的：研究rs3923113-GRB14,rs1802295-VPS26A,rs7178572-HMG20A三基因单核苷酸多态性（SNPs）与2型糖尿病（T2DM）及相关代谢指标的相关性。方法：用高分辨率溶解曲线（HRM）小片段基因分型方法检测300例T2DM者及300例健康体检者3SNP位点基因型及等位基因频率分布。结果：各SNP基因型分布符合遗传平衡定律。rs231362（KCNQl）的风险基因C患病风险是T等位基因的1．058倍（P=0．012,OR=1．058,95％CI：1．012-1．106）。rs231362（KCNQl）的3种基因型（TT、CT、CC）在T2DM组与对照组中的分布频率分别为0．7％、19．9％、75．6Voo和2．7％、25．6％、71．7％,2组基因型分布差异有统计学意义（P=0．031）。该位点在其隐性模型中（CCVSCT＋TT）,2组差异有统计学意义（P=0．028,OR=1．11,95％CI：1．01～1．22）。rs3923113-GRBl4、rs7178572-HMG20A基因型分布在病例组与对照组中未见显著性差异。我们分析了对照组血糖血脂与各SNP位点基因型之间的关系,rs3923113在显性模型[（TT＋GT）／GG]下TT＋GT组总胆固醇（Tc）值低于GG组;TT＋GT组高密度脂蛋白（HDL-C）1．07（0．90-1．19）mmol／L低于GG组1．21（1.02-1．41）mmol／L,P值分别为0．017与0．036。结论：rs231362-KCNQl可能与中国人群T2DM发病有关。rs3923113-GRBl4与TC及HDL-C升高有关。     

PPAR5基因＋294T／C多态性与2型糖尿病患者血脂和胰岛功能关系研究

目的研究2型糖尿病（T2DM）患者和糖耐量正常（NGT）者中PPARδ基因＋294T／C多态性与血脂和胰岛功能的关系。方法选取346例南京地区汉族人群，其中新诊断T2DM患者236名，NGT者110名，用Touch-down PCR检测PPAR5＋294T／C基因变异，并检测人选人群的临床指标。结果T2DM组中携带C等位基因（TC＋CC）者HOMA-β水平低于TT型（P〈0．05）；NGT人群中，携带C等位基因（TC＋CC）者LDL-C／HDL-C比值高于TT型（P〈0.05），Pearson相关分析显示NGT组携带C等位基因与LDL-C、LDL-C／HDL—C水平呈正相关（P〈0．05）。结论T2DM患者携带PPAR5＋294C等位基因者胰岛素分泌能力下降，在NGT组中PPAR5＋294T／C与脂代谢紊乱相关。     

金属硫蛋白1E基因多态性与2型糖尿病的关系

目的探讨金属硫蛋白（MT）IE基因多态性与2型糖尿病（T2DM）的关系。方法采用PCR-RFLP法检测149例T2DM患者和244例正常对照者的MTIE基因上的一个SNP-rs 8708274，应用SPSS统计学软件处理数据，进行统计学分析。结果病例组和对照组等位基因T和G比较差异有显著性（x^2=4．072，P〈0．05）；TT，TG，GG三种基因型频数分布在病例组和对照组中存在差异（x^2=8．252，P〈0．05）。结论在中国北方汉族人群中MTIE rs 708274位点基因多态性可能与T2DM相关。     

亚甲基四氢叶酸还原酶基因C677T突变与高尿酸血症的相关性研究

目的探讨高尿酸血症（HUM）与亚甲基四氢叶酸还原酶（MTHFR）基因C677T突变及高血糖、肥胖和高血压等的相关性。方法从青岛地区糖尿病流行病学调查数据库中，随机选取HUM＋T2DM患者79例、HUM无T2DM患者（HUM组）90例、并选取T2DM无HUA患者（DM组）90例和健康对照（NC）91例。采用聚合酶链反应-限制性片段长度多态性技术检测MTHFR基因突变。结果HUM组和HUM＋T2DM组MTHFR677T等位基因频率分别为46．7％和51．3％，TT基因型频率分别为23．3％和26．6％，两组差异无统计学意义（P〉0．05）；T等位基因和TT基因型频率在NC组和DM组间差异无统计学意义（P〉0．05）；而HUM组和HUM＋T2DM组MTHFR677T等位基因型频率和TT基因型频率均分别高于NC组和DM组（P〈0．005）。CT和TT基因型患者平均血尿酸水平（分别为394．2μmol／L和465．8μmol／L）明显高于CC基因型者（347．3μmol／L）（P〈0．05）。多因素logistic回归分析表明，调整BMI、SBP、TG、TC及饮酒等因素后显示，MTHFR基因型是HUM患病的独立危险因素。结论MTHFR基因C677T突变是青岛地区人群发生HUM的独立危险因素。     

血管内皮生长因子基因多态性与糖尿病视网膜病变的相关性

目的探讨血管内皮生长因子（VEGF）-460C/T基因多态性与糖尿病视网膜病变（DR）的相关性。方法病史超过10年的2型糖尿病（T2DM）患者204例,分为非增殖型视网膜病变组（NP-DR,65例）、增殖型视网膜病变组（PDR,64例）及单纯2型糖尿病组（DM,75例）。用PCR-RFLP方法检测各组基因型,比较各组基因型和等位基因的频率。结果DR组VEGF-460位点TT基因型频率显著低于DM组（P〈0.01）,C等位基因频率显著高于DM组（P〈0.01）;NPDR组与PDR组基因型和等位基因频率差异无统计学意义（P〉0.05）。DM中CC、CT、TT基因型的DR发生率分别为69.8%、68.9%和42.2%,CC和CT基因型的DR发生率显著高于TT基因型（P〈0.01）。结论VEGF-460C/T多态性与DR的发生发展有关,C等位基因可能是DR的易感基因。     

脂联素基因SNP-11377多态性与冠脉病变程度相关性研究

目的探讨在中国上海地区汉族人群中脂联素基因（APM1）启动子序列单核苷酸多态性（SNP）与冠脉病变程度的关系。方法采用聚合酶链反应-限制性片段长度多态性（PCR—RFLP）方法，分析了325例冠脉造影结果和脂联素启动子序列单核苷酸多态性（-11377G／C）的关系．研究设立了冠心病组（CAD）和正常对照组，并根据冠脉造影结果按照不同病变支数及Gensini评分将分成不同病变组，分析-11377位点基因型及基因频率的差异性。结果（1）冠心病组脂联素基因-11377位点多态性GC、GG基因型频率与对照组比较，显著高于对照组，差异有极显著性（χ^2=12．619，P〈0．05）；（2）冠心病患者脂联素-11377位点G等位基因频率显著高于正常人（χ^2=11．291，P〈0．05）；（3）根据冠脉造影结果冠脉不同病变支数各组比较，脂联素-11377位点基因型差异无显著性（χ^2=11．575，P〉0．05），而等位基因频率具有显著差异性（χ^2=11．582，P〈0．05）；（4）按Genisini标准冠状动脉不同积分各组之间比较脂联素基因型间差异无显著性（χ^2=10．983，P〉0．05），但等位基因频率具有显著差异性（χ^2=8．978，P〈0．05）。结论脂联素SNP-11377G／C各种基因型与冠心病有关，与冠状动脉粥样硬化病变程度无关，而等位基因频率不但与冠心病显著相关，并且与冠状动脉病变程度有关。     

eNOS基因5'侧翼区T-786C多态性与冠心病的相关性研究

目的探讨内皮型一氧化氮合酶（eNOS）基因5’侧翼区T-786C多态性与中国汉族人冠心病和冠状动脉狭窄支数的关系。方法依据eNOS基因5’侧翼区T-786C位点设计引物，应用多聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析方法检测136例经冠状动脉造影证实的冠心病（冠心病组）和77例非冠心病（对照组）患者的eNOS基因T-786C多态性。结果（1）冠心病组TT＋TC和CC基因型频率分别为72．8％、25．7％、1．5％，对照组分别为92．2％、6．7％、0（χ^2=11．5，P〈0．01）；（2）冠心病组C等位基因的频率高于对照组C等位基因的频率（14．3％比3．9％，χ^2=11．5，P〈0．01）；（3）多元logistic回归显示eNOS T-786C基因多态性是冠心病的独立危险因素（OR值5．261，95％CI：2．010～13．768）；（4）在1、2、3支冠脉血管狭窄组中。TC＋CC基因型频率分布分别为21．4％、25．0％和33．3％（χ^2=1．83，P〉0．05），C等位基因频率分别为10．7％、12．5％、18．5％（χ^2=2．66，P〉0．05）。结论（1）eNOS T-786C基因多态性是冠心病的遗传危险因素，并独立于冠心病其它的经典危险因素；（2）eNOS T-786C基因多态性与冠脉狭窄的支数元关。     

TCF7L2基因rs290487多态性与2型糖尿病相关研究

采用PCR—RFLP技术,对100例正常个体和100例T2DM患者的TCF7L2基因rs290487多态性进行检测,结果：在病例组和对照组TCF7L2的多态性位点rs290487等位基因的频数分布差异无统计学意义（x^2=0．251,P〉0．05）;基因型的频数分布差异无统计学意义（x^2=0．248,P〉0．05）。Logistic回归显示,与CC基因型比较,携带突变等位基因T的基因型（CT和TT）并没有改变患T2DM的风险,该多态性与T2DM的易感性关联无统计学意义。结论：在中国济南地区人群的TCF7L2基因rs290487多态性可能与T2DM无关     

乙酰辅酶A羧化酶β基因多态性与2型糖尿病易感性关系的初步研究

目的 研究上海地区汉族人群中乙酰辅酶A羧化酶B（ACC-β）的2个单核苷酸多态性（SNP）位点与2型糖尿病（T2DM）易感性的关系。方法 采用等位基因专一性实时PCR的方法对上海地区438例T2DM患者及328名正常对照者（NC）ACC-β基因的2个SNP位点进行分析。结果 （1）ACC-β基因16号内含子区存在SNP位点116／73C＞T，T2DM组和NC组两组间基因型频率比较，差异有统计学意义（P=0．031）。且CC型＋CT型与TT型的分组比较在两组间的差异也有统计学意义（P=0．027）。（2）ACC-B基因16号内含子区还存在另-SNP位点：116／288A〉G，T2DM组G等位基因的频率高于NC组，但无统计学意义。结论 在上海地区的汉族人群中，ACC-β基因可能是T2DM的易感基因之一，其16号内含子区的116／73C＞T多态性（rs2268393）可能与T2DM的发病相关。     

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.     

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.     

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.