PDGF及其基因多态性与冠状动脉粥样斑块易感相关性研究

目的:探讨血小板衍化生长因子(PDGF)血清学水平及PDGF-D rs3809021、rs974819位点基因多态性与冠状动脉粥样硬化斑块性质遗传易感性的关系。方法:237例冠心病(CHD)患者根据冠脉造影及血管内超声检查(IVUS)结果将粥样斑块分为稳定斑块组(65例)、易损斑块组(89例)、混合斑块组(83例),采用双抗体夹心酶联免疫吸附法(ELISA法)检测血清PDGF水平;应用聚合酶链反应(PCR)技术检测PDGF-D rs3809021、rs974819基因多态性及测序鉴定,并与112例正常者对照。结果:CHD各亚组PDGF水平均高于对照组;易损斑块组、混合斑块组血清PDGF水平均显著高于稳定斑块组。PDGF-D基因rs3809021位点多态性在CHD组和对照组的分布差异无统计学意义。PDGF-D基因rs974819位点中,携带C等位基因的基因型(CG+CC)可增加总体CHD发病风险,CHD亚组间基因频率分布特点为稳定斑块组与易损斑块组、混合斑块组相比较,差异有统计学意义。结论:PDGF-D rs974819位点基因多态性与冠状动脉粥样硬化斑块性质的相关,C等位基因使易损斑块的发生率增加,rs974819位点C等位基因可能是CHD的遗传易感基因。     

血小板衍化生长因子-D基因多态性与冠状动脉粥样斑块的相关性

目的探讨血小板衍化生长因子(PDGF)-D rs7950273位点基因多态性与冠状动脉粥样硬化斑块性质的相关性。方法 237例冠心病(CHD)患者根据冠脉造影及血管内超声检查(IVUS)结果将粥样斑块分为稳定斑块组(65例)、易损斑块组(89例)、混合斑块组(83例),采用聚合酶链反应(PCR)技术检测PDGF-D rs7950273基因多态性及测序鉴定,并选择112例正常者为对照。结果 CHD组(62例,26.2%)CC基因型频率显著高于对照组(16例,14.2%),而对照组GG基因(39例,34.8%)高于CHD组(43例,18.1%)。CHD组C等位基因频率(256例,54.1%)明显高于对照组(89例,39.7%)。CHD亚组间基因频率分布特点为稳定斑块组与易损斑块组、混合斑块组差异显著(P0.05)。结论 PDGF-D rs7950273位点基因多态性与冠状动脉粥样硬化斑块性质的相关,C等位基因使易损斑块的发生率增加。     

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。     

ASP基因rs2250656位点多态性与新疆汉族及少数民族脂质代谢及冠心病严重程度的相关性研究

目的:探讨ASP基因rs2250656位点多态性与新疆汉族及少数民族脂质代谢及冠心病严重程度的相关性。方法:纳入新疆地区冠心病患者818例,其中汉族组489例,少数民族组329例。采用SNPscanTM高通量基因分型技术检测所纳入患者基因多态性,并检测血脂水平及冠状动脉(冠脉)病变程度。结果:ASP基因rs2250656位点TT基因型汉族组(61.8%)明显高于少数民族组(52.9%),TC基因型少数民族组(32.9%)明显高于汉族组(41.3%),分布差异有统计学意义(P<0.05),两组等位基因T与C频率分布差异有统计学意义(P<0.05)。少数民族组基因型亚组间的甘油三酯水平差异有统计学意义(P<0.05),其中CC基因型甘油三酯水平明显高于TT基因型及TC基因型;少数民族组基因型亚组间的冠脉病变程度差异有统计学意义(P<0.05),其中CC基因型病变严重程度高于TT基因型及TC基因型。结论:ASP基因rs2250656位点C等位基因与少数民族冠心病患者甘油三酯增高有一定相关性,CC基因型可能是少数民族冠心病的危险因素之一,而其与汉族冠心病的发病可能无一定...     

CTRP9基因多态性与冠心病的相关性

目的探讨广东地区汉族人群CTRP9基因多态性与冠心病遗传易感的相关性。方法入选冠心病患者548例和对照个体862例,利用聚合酶链式反应-连接酶检测反应(PCR-LDR)技术检测CTRP9基因的两个多态性位点rs6583、rs9553238的基因型,并采用Logistic回归分析两个多态位点和冠心病的易感性。结果 rs6583和rs9553238的等位基因、基因型频率在广东地区汉族人群的冠心病组和对照组分布中均无统计学差异(P>0.05),构建的显性模型、隐性模型、加性模型在冠心病组和对照组中也无统计学差异(P>0.05);CTRP9基因单体型(rs6583-rs9553238)在这两组中仍未发现有统计学差异(P>0.05)。结论 CTRP9基因rs6583和rs9553238多态位点与广东地区汉族人群的冠心病遗传易感无显著相关性。     

趋化因子CX3C受体1基因rs3732378多态性与急性冠状动脉综合征的相关性

目的探讨趋化因子CX3C受体1(CX3CR1)基因rs3732378单核苷酸多态性与急性冠状动脉综合征(ACS)的相关性。方法连续收集中国北方汉族人群951例,其中男性520例,女性431例,年龄35~75岁。根据冠状动脉造影(CAG)结果分为2组:(1)病例组(n=512):ACS患者;(2)对照组(n=439):非冠心病患者。病例组根据CAG检查血管病变支数分为3个亚组。采用测序法测定CX3CR1基因rs3732378单核苷酸多态位点的基因型。用多因素Logistic回归分析CX3CR1基因rs3732378多态性与ACS发病风险的关系。应用酶联免疫吸附法检测血浆中趋化因子CX3C配体1(CX3CL1)表达水平。结果两组CX3CR1基因rs3732378的基因型及等位基因的分布频率无显著性差异(P0.05)。rs3732378多态位点与ACS发病风险的总体和分层分析结果表明,CX3CR1基因rs3732378多态位点的3种基因型TT、TC和CC均不能增加ACS的发病风险(P0.05)。亚组分析显示,rs3732378多态位点的基因型和等位基因与冠状动脉血管病变支数无相关性(χ2=0.135,P=0.998;χ2=0.026,P=0.987)。病例组和对照组血浆中CX3CL1表达水平在rs3732378三种基因型无差异(P0.05)。结论 CX3CR1基因rs3732378多态位点不是ACS的易感基因,rs3732378多态性没有增加中国北方汉族人群ACS的风险。     

结缔组织生长因子rs9399005单核苷酸多态性与冠心病的关系

目的探讨结缔组织生长因子(CTGF)rs9399005基因多态性与血清CTGF水平及冠心病的相关性。方法纳入冠心病组214例和正常对照组64例,酶联免疫吸附法检测其血清CTGF水平。采用Sanger法分析CTGF基因rs9399005单核苷酸多态性(SNP)。比较两组基线临床资料、血清CTGF和基因型分布频率。非条件Logistic回归分析CTGF rs9399005 SNP与冠心病的遗传易感性,比较不同基因型CTGF水平。分析CTGF水平与冠状动脉病变支数、冠心病严重程度的关系。结果两组年龄、吸烟、高血压、体质指数、高密度脂蛋白胆固醇、载脂蛋白A1、CTGF差异有统计学意义(P0.05)。rs9399005基因型CC、CT、TT及等位基因C和T在两组间的分布有统计学差异(χ2值分别为12.935和17.148,均P0.01)。携带CT发生冠心病的危险性是CC的1.134倍,TT是CC的1.406倍,T等位基因是C等位基因的1.327倍。血清CTGF水平在各基因型间差异有统计学意义(F=3.284,P=0.034)。各基因型间冠心病所累及的冠状动脉主要分支的差异有统计学意义(χ2=13.872,P=0.022)。结论CTGF rs9399005 SNP与冠心病的遗传易感性相关;等位基因T与冠心病严重程度、冠状动脉病变支数及血清CTGF水平相关。     

PHACTR1基因多态性与皖北地区汉族人群冠心病的相关性

目的探讨PHACTR1基因rs2026458、rs9349379位点多态性与皖北地区汉族人群冠状动脉粥样硬化性心脏病(冠心病,CHD)的相关性。方法纳入2017年12月至2018年12月于蚌埠医学院第一附属医院心血管科住院的冠心病患者为CHD组(n=93),选取同期在此医院经心电图和病史排除冠心病的体检者为对照组(n=104)。采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)技术检测两组人员rs2026458及rs9349379位点的基因型和等位基因分布。结果两组人员rsl761667位点及rs10499859位点的等位基因频率及基因型相比,差异均无统计学意义(P0.05)。与对照组相比,CHD组年龄较大,体重、高血压、2型糖尿病、吸烟史、Hb A1c、TG、LDL等指标显著高于对照组,HDL显著低于对照组,差异均有统计学意义(P0.05)。Logistic回归分析显示,低密度脂蛋白胆固醇是冠心病发生的独立危险因素(P0.05)。结论皖北地区汉族人群PHACTR1基因rs2026458和rs9349379位点多态性可能与冠心病的发生无关。     

CYP17A1基因多态性与冠心病遗传易感性的研究

目的探讨CYP17A1(rs4409766,rs1004467)基因多态性与冠状动脉粥样硬化性心脏病(冠心病)遗传易感性之间的关系。方法选取2014年6月~2016年2月于青岛大学附属医院心血管内科住院并行冠状动脉造影诊断为冠心病和非冠心病的患者为研究对象,应用实时荧光定量PCR(q RT-PCR)技术对冠心病患者88例(CHD组)和非冠心病患者89例(非CHD组),进行CYP17A1基因rs4409766,rs1004467的SNP分析,比较基因型频率及等位基因频率在2组间的分布。结果 CYP17A1基因rs4409766位点的基因型分布在CHD组和非CHD组之间无差别(P0.05),但是CC与CT+TT基因型分布比较两组间差异有统计学意义(P=0.038);rs1004467位点的基因型和等位基因分布在CHD组和非CHD组之间差异无统计学意义(P0.05)。结论 CYP17A1的rs4409766位点的基因多态性与冠心病的发生有关联。     

壮族冠心病患者的TLR4表达水平及其rs4986790A/G、rs4986791C/T位点的多态性分析

目的探讨广西壮族冠心病(CHD)患者的TLR4蛋白表达水平及其rs4986790A/G、rs4986791C/T位点的多态性。方法选取2016年1月至2018年1月在我院行冠状动脉造影(CAG)检查被确诊为CHD的壮族患者245例为CHD组,选取同期在我院住院治疗的245例非CHD患者为对照组。采用酶联免疫吸附法(ELISA)检测两组患者的血清TLR4蛋白表达水平;采用SNaPshot测序技术检测两组患者外周血TLR4基因rs4986790A/G、rs4986791C/T位点的基因型及等位基因。分析TLR4蛋白表达水平及其rs4986790A/G、rs4986791C/T位点的多态性与壮族人群CHD发病的相关性。结果 CHD组患者的外周血TLR4蛋白表达水平高于对照组,差异有统计学意义(P0.05)。CHD组患者的TLR4基因rs4986790A/G、rs4986791C/T位点的等位基因及基因型频率分布与对照组患者比较,差异无统计学意义(P0.05)。结论外周血TLR4蛋白表达水平与广西壮族人群CHD的发生存在关联,但TLR4基因rs4986790A/G、rs4986791C/T位点的多态性可能与壮族人群CHD冠心病发病无明显的相关性。     

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.