白细胞介素-1β基因启动子-31位点单核苷酸多态性与甲型H1N1流感易感性的关联分析

目的 探讨白细胞介素-1β(IL-1β)基因启动子-31位点单核苷酸多态性(SNP)与甲型H1N1流感易感性的关系.方法 采用病例-对照研究方法,应用TaqMan探针技术,对167例H1N1流感患者和192例健康对照人群IL-1β基因-31位点进行等位基因分型,比较两组人群基因型分布及频率差异.结果 IL-1β基因-31位点具有T和C两种等位基因,其中H1N1流感组T、C等位基因频率分别为38.3%和61.7%,对照组T、C等位基因频率分别为54.4%和45.6%,两组差异具有统计学意义(P<0.001,OR=1.922,95% CI 1.426-2.590).结论 IL-1β基因启动子-31多态性位点与甲型H1N1流感易感性相关,C等位基因是甲型H1N1流感易感基因.     

中国沿海地区汉族男性人群白细胞介素-1β-511C/T基因多态性与痛风的易感性研究

目的 探讨中国山东省沿海地区汉族男性群体的白细胞介素(IL)-1β-511位点的多态性是否与痛风的易感性有关.方法 采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)检测276例痛风患者和268名健康对照者的IL-1β-511位点的基因多态性分布.统计学处理采用x2检验和t检验.结果 IL-1β启动子区-511位点CC、CT和TT基因型频率在痛风组与健康对照组相比差异无统计学意义(x2=3.251,P=0.197,df=2);2组的等位基因频率C和T间差异也无统计学意义(x2=2.941,P=0.086,OR=1.232,95％CI=0.971～1.563).经x2检验,IL-1β基因-511C/T位点基因多态性与痛风病的危险因素无相关性.痛风组与健康对照组相比,具有较高的体质量指数(BMI)、血压水平、血尿酸、血糖、甘油三酯及胆固醇水平,差异有统计学意义(P＜001).结论 中国沿海地区汉族男性人群中IL-1β-511C/T基因多态性与痛风的易感性无关联性.     

血红素氧合酶1基因－413A/T位点多态性与血脂异常个体冠心病患病风险密切相关

目的检测血红素氧合酶1基因启动子区-413A/T位点多态性,阐明血红素氧合酶1基因多态性与冠心病易感性的关联。方法选择经冠状动脉造影确诊的冠心病患者200例为病例组,冠状动脉无明显狭窄、年龄、性别与病例组相仿的120例个体为对照。启动子区直接测序方法检测-413A/T单核苷酸多态性基因型。以冠心病危险因素作为协变量,统计血红素氧合酶1基因-413A/T位点多态性与冠心病的相关性。结果研究人群-413位点为单核苷酸多态性位点,且携带TT基因型的血脂异常患者冠心病患病风险明显减少(校正后OR=0.179,95%CI=0.05～0.642)。结论血红素氧合酶1基因启动子区-413A/T可能是评价血脂异常个体冠心病易感性风险的重要标记。     

白细胞介素6基因启动子区-572位点多态性与男性肝细胞癌的发生相关

目的 探讨白细胞介素(IL)6基因启动子区-572位点多态性与男性肝细胞癌(HCC)发生的关系.方法 采用以医院为基础的病例对照研究,以500例经肝组织病理学诊断为HCC,且无其他器官肿瘤史的男性患者作为病例组,以同期来自相同医院创伤骨科和眼科的无肿瘤病史、无长期慢性疾病史的男性患者590例作为对照组.应用ABI 7500fast实时荧光定量PCR仪对IL-6基因启动子区-572位点多态性进行分型.采用x2检验和非条件logistc回归模型比较携带不同基因型人群罹患HCC的风险,logistic回归模型进行交互作用分析.结果 -572位点G/C等位基因、各基因型频率在病例组和对照组中的分布差异均无统计学意义(P＞0.05);多因素logistc回归分析发现,男性携带G等位基因个体(CG+GG)HCC发生风险是CC基因型的1.31倍(95％CI为1.00～1.71).分层分析显示,在HBV感染者中与CC基因型相比,男性携带CG基因型能增加HCC发生的风险(OR=1.60,95％ CI为1.14 ～2.24);趋势x2检验结果显示,个体HCC发生风险随携带等位基因G数量的增加而升高(Ptrend＜0.05).Brelow-Day一致性检验发现HBV感染与IL-6多态性具有交互作用(P＜0.05),HBV感染与携带G等位基因同时存在时的OReg=5.95 (95％ CI为3.99～8.87),且为超相乘交互作用.结论 男性IL-6基因启动子区-572位点多态性可能与HCC发生相关.男性携带G等位基因与HBV感染有超相乘交互作用,两者同时存在可能增加男性HCC发生的风险.     

IL-10基因多态性与乙肝肝硬化易感性的相关性研究

探讨白细胞介素10(IL-10)基因多态性与乙型肝炎肝硬化易感性的关系.采用聚合酶链反应-限制性片段长度多态性(PCR-PFLP)分析方法,检测100例乙肝肝硬化患者及124例健康对照组IL-10基因启动子-1082G/A、-592A/C位点的基因多态性,并确定了其基因型和等位基因频率的分布.肝硬化组与对照组IL-10基因启动子-592A/C位点基因型分布频率和等位基因频率差异无显著性(P＞0.1),肝硬化组-1082G/A位点AA基因型频率及A等位基因频率高于对照组(P＜0.05),G等位基因相对于A等位基因患肝硬化的机会比为0.373(95%CI:0.166～0.838).IL-10基因多态性与肝硬化易感性相关,基因启动子-1082G/A位点AA基因型携带者肝硬化易感性高.     

去整合素金属蛋白酶10基因启动子区多态性变化与腔隙性脑梗死发病风险的关系

目的观察腔隙性脑梗死患者去整合素金属蛋白酶（ADAM）10基因启动子区多态性变化,分析此多态性变化与腔隙性脑梗死发病风险的关系。方法研究对象为173例腔隙性脑梗死患者（梗死组）和297例非脑血管病体检者（对照组）,采用Snapshot分型技术检测ADAMIO基因启动子区rs653765和rs514049位点多态性,采用B型彩色多普勒超声仪测量颈动脉内膜中层厚度（CIMT）;比较两组位点多态性及其与梗死组性别、年龄、CIMT的关系。结果梗死组ADAMIO基因rs653765位点CC基因型频率显著低于对照组（P=0．0080）、隐性模型CT＋TT基因型频率显著高于对照组（OR：0．54,95％a为0．36—0．81,P=0．0029）,T等位基因频率显著高于对照组（OR=1．95,95％CI为1．37～2．79,P=0．0002）;两组ADAMl0基因rs514049位点的基因型频率和等位基因频率无显著差异（P〉0．05）。携带ADAMIO基因rs653765位点T等位基因的男性发生腔隙性脑梗死的风险显著升高（OR=1．51,95％CI为1．00—2．28,P=0．048）,而≥70岁人群中携带cT基因型或T等位基因者发生腔隙性脑梗死的风险显著升高（OR=1．69,95％CI为1．00—2．85,P=0．046）;ADAMl0基因rs653765和rs514049位点的多态性与腔隙性脑梗死患者cI．MT无明显相关。结论ADAMl0基因rs653765位点T等位基因可能与腔隙性脑梗死的发病有关。     

DNMT3B基因SNP (-149C/T)与佳木斯地区肺癌发病风险的关系

目的 探讨DNMT3B基因启动子-149C/T(C46359T)单核苷酸多态性与佳木斯地区人群肺癌易感性的相关性.方法 提取50例肺癌患者及60例健康体检人员外周血基因组DNA,采用PCR-RFLP结合DNA测序技术检测DNMT3B基因启动子单核苷酸多态性-149C/T( C46359T).结果 正常对照组DNMT3B-149C/T等位基因TT/CT/CC基因型颇为97％／3％／0,病例组分别为96％／2％／2％.携带有SNP(-149C/T) C→T转换的个体患肺癌的易感性未见明显升高(x2 =0.11,P＞0.05,OR=0.83,95％CI:0.27～2.50).结论 DNMT3B基因C46359T多态性可能不适合作为佳木斯地区人群肺癌易感性的一个独立风险因素.     

环氧合酶-2基因启动子区单核苷酸多态性与非酒精性脂肪肝遗传易感性的关系

目的 通过检测环氧合酶-2(COX-2)基因启动子区单核苷酸的多态性,以探讨其与非酒精性脂肪肝(NAFLD)遗传易感性的关系.方法 对200例NAFLD患者和206名正常对照,采用多聚酶链反应-限制性片段长度多态性(PCR-RFLP)方法对COX-2基因启动子区-765G＞C和-1195G＞A多态性进行基因型分析.计量资料结果用均数±标准差((-x)±s)表示,经方差齐性检验后,行t检验;性别、基因型及等位基因频率的比较行x2检验.结果 正常对照中,COX-2基因启动子区-765G＞C和-1195G＞A等位基因的分布频率分别为48%和2%,NAFLD患者组二者分别为54%和5%.多变量Logistic回归分析显示:-765GC基因携带者与-765GG基因携带者相比较,前者发生NAFLD的比值比(OR)=2.35 (95% CI为1.17～3.65);-1195AA基因携带者与-1195GG基因携带者相比较,前者发生NAFLD的OR=1.13 (95% CI为1.01～2.46).与单体型G-1195-G765相比较,含有A1195的A-1195-C-765、A1195-G765两种单体型发生NAFLD的相对风险明显升高,OR分别为1.42 (95% CI为1.11～1.63,P＜0.05)和4.24(95% CI为1.72～14.22,P＜0.01).且A-1195-C765发生NAFLD的OR值高于A-1195-G-765、G-1195-C765的单体型.这一结果提示在同一单体型内-1195A与-765C之间存在交互作用.结论 COX-2基因启动子区的-1195G＞A和-765G＞C单核苷酸存在多态性,与NAFLD发生相关,是决定NAFLD个体遗传易感性的重要因素.     

IL-18启动子区-137G/C和-607C/A位点多态性与结核病易感性关系——Meta分析

目的 应用Meta分析探讨IL-18基因启动子区单核苷酸多态性（single nucleotide polymorphism,SNP）等位基因位点-137和 -607与结核病易感性的关系。方法 收集采用序列特异性引物聚合酶链反应（PCR-SSP）及测序技术检测SNP位点-137和 -607的研究,在严格的质量评价基础上,通过统计学方法应用Review Manager 5.0软件进行了Meta分析。入选文献标准：(1)关于IL-18启动子区SNP -137 G/C和(或) -607 C/A与结核易感性关联的病例-对照研究;（2）对照组基因分布符合Hardy-Weinberg（H-W）遗传平衡定律;（3）原始资料完整;（4）文献中提供基因型频率或等位基因频率;（5）纳入文献语言为中文或英文;（6）多态性检测方法通过PCR-SSP及测序技术或SNaPshot SNP分型方法。文献排除标准：（1）重复报告的研究;（2）数据不清或等位基因不清的文献;（3）基于家系的研究;（4）对照组基因分布没有进行H-W遗传平衡检验的研究。结果 IL-18启动子区SNP -607 C/A位点研究6项,患者695例,正常对照879例;SNP -137 G/C位点研究5项,患者594例,正常对照781例。结核病组IL-18启动子区等位基因-137 G和 -607 C与对照组相比,等位基因-137 C和 -607 A的合并OR值分别为1.41（95% CI为1.15～1.74,P=0.001）和0.93（95% CI为0.81～1.08,P=0.36）。结论 IL-18启动子区SNP位点-137 G/C与结核病易感性相关联,提示IL-18启动子SNP（-137）是结核病的易感位点之一; SNP位点-607 C/A与结核病易感性之间关联无统计学意义。     

VEGF基因-460T/C与-634G/C多态性位点单倍型与ACI易感关联研究

目的 探讨血管内皮细胞生长因子(VEGF)基因启动子区-460T/C与-634G/C多态性位点单倍型在中国汉族人群中与动脉粥样硬化性脑梗死(ACI)的关联.方法 采用PCR-限制性片段长度多态性技术(PCR-RFLP)检测165例ACI患者和198例健康对照者VEGF基因-460T/C与634G/C多态性.并利用PHASE2.3软件构建其单倍体型,以非条件Logistic回归校正混杂因素,并进行单倍型与ACI对患者及其他风险因素的统计学分层分析.结果 VEGF基因-460T/C与-634G/C多态性位点的基因频率分布符合Hardy·Weinberg平衡定律;VEGF基因-460C与-634C组成的C-C单倍型频率在两组人群中的比较有显著性差异,P=0.002,OR=3.86;分层分析中发现:合并高血压(P<0.001,OR=4.16)、高脂血症(P<0.001,OR=6.42)的患者其易感性更为显著.结论 VEGF基因启动子区-460T/C与-634G/C多态性位点组成的单倍型C-C与ACI有着明显的易感关联,而合并有高血压或者高脂血症的患者使易感性关联更为增强.     

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.