微小RNA-146a C＞G多态性与缺血性卒中风险:汇总分析

目的 探讨微小RNA-146a(microRNA-146a,miR-146a)C＞G多态性与缺血性卒中的关联性.方法 全面检索2016年2月以前发表的miR-146a C＞G多态性与缺血性卒中关系的病例对照研究,应用Stata 12.0软件包进行汇总分析,利用优势比(odds ratio,OR)和95％可信区间(confidence interval,CI)评价miR-146a C＞G多态性与缺血性卒中风险的关联强度.结果 共纳入8篇文献,病例组2 891例,对照组4 019例,入选文献无明显发表偏倚.在总体人群中,显性模型(GG+ CG对CC:OR 1.011,95％ CI0.863～1.185;P=0.889)、隐性模型(GG对CG+ CC:OR 0.999,95％ CI0.761 ～1.311;P=0.994)、杂合子模型(CG对CC:OR1.052,95％CI0.943～ 1.173;P=0.368)、纯合子模型(GG对CC:OR1.114,95％ CI0.819 ～ 1.515;P=0.491)和等位基因模型(G/C:OR1.062,95％ CI0.919～1.227;P=0.413)均未显示miR-146a C＞G多态性与缺血性卒中风险存在显著相关性.亚组分析显示,miR-146a C＞G多态性与大动脉粥样硬化性和小动脉闭塞性卒中的发病风险亦无显著相关性.结论 根据目前的文献,miR-146a C＞G多态性可能与缺血性卒中风险无显著关联性.     

SERPING1基因rs2511989位点基因多态性与老年性黄斑变性易感性的Meta分析

目的用Meta分析定量评价SERPING1基因rs2511989位点基因多态性与老年性黄斑变性(AMD)易感性的相关性。方法计算机检索Embase、PubMed、Cochrane Library、中国生物医学文献数据库(CBM)、CNKI数据库、重庆维普数据库及万方数据库,收集SERPING1基因rs2511989位点基因多态性与AMD易感性的病例对照试验。计算各种基因模型下的比值比(OR)和95%CI,采用STATA10. 0软件进行统计分析。结果最终纳入7篇病例对照研究进行Meta分析,其中病例组共纳入2 800例AMD患者,对照组共纳入2 221例健康志愿者。Meta分析结果显示,两组杂合子模型(GG vs GA:OR=1. 23,95%CI为1. 08～1. 40)、显性模型(AA vs GA+GG:OR=1. 24,95%CI为1. 01～1. 52)差异有统计学意义(P0. 05);隐性模型(AA vs GA+GG:OR=0. 85,95%CI为0. 61～1. 17)、纯合子模型(GG vs AA:OR=1. 38,95%CI为0. 94～2. 00)、杂合子模型(GA vs AA:OR=1. 12,95%CI为0. 91～1. 37)差异无统计学意义(P0. 05)。结论 SERPING1基因rs2511989位点与AMD的易感性可能无相关性。     

ADAM33基因S1和S2多态性与哮喘易感性关联的Meta分析

目的探讨整合素和金属蛋白酶域33(ADAM33)基因S1(rs3918396 GA)和S2(rs528557 GC)多态性与哮喘易感性的相关性。方法检索CBM、维普、万方、CNKI、Pub Med、Embase、Google学术、Web of Science等电子数据库,检索范围从建库至2013年8月,采用STATA 12.0软件计算优势比(OR)及其95%可信区间(95%CI)。结果共计纳入10项病例对照研究,包括5 777例哮喘患者和6 800例健康对照人群。Meta分析结果表明:ADAM33基因S2多态性与哮喘易感性增加有关(G vs.C:OR=1.17,95%CI:1.10~1.24,P0.001;GG+GC vs.CC:OR=1.35,95%CI:1.20~1.53,P0.001),但S1多态性与哮喘易感性无明确统计学关联(G vs.A:OR=0.92,95%CI:0.71~1.18,P=0.502;GG+GC vs.CC:OR=0.76,95%CI:0.45~1.27,P=0.295)。根据种族不同进行亚组分析发现,ADAM33基因S2多态性与亚洲人群和欧美人群哮喘易感性增加均有关联(P均0.05)。然而ADAM33基因S1多态性与不同种族人群哮喘易感性均无显著关联(均P0.05)。结论 ADAM33 S2多态性可能与哮喘易感性增加有关,它可以作为早期诊断哮喘的重要分子标志物。     

IL-17A基因多态性与自身免疫性疾病易感性关系的Meta分析

目的探讨IL-17A基因多态性与自身免疫性疾病(autoimmune disease,AID)易感性的关系。方法计算机检索数据库,收集有关IL-17A基因多态性与AID易感性病例-对照研究,文献相关数据进行Meta分析,以病例组与对照组IL-17A基因多态性不同位点各种基因模型的比值比(OR)及95%CI为效应指标,并根据研究病种进行亚组分析。结果共14项研究符合纳入标准。Meta分析表明IL-17A rs2275913G/C多态性与AID易感性无明显相关性[AA vs GG:OR=0.963,95%CI:0.862~1.076,P=0.508;GA vs GG:OR=0.913,95%CI:0.741~1.126,P=0.395;GA/AA vs GG:OR=0.960,95%CI:0.868~1.062,P=0.431;AA vs GG/GA:OR=1.015,95%CI:0.916~1.124,P=0.781]。亚组分析表明IL-17A rs2275913G/C多态性与炎性肠疾病易感性无明显相关性。结论 IL-17A rs2275913G/C多态性与自身免疫性疾病无明显相关性。     

RNF213基因多态性与颅内血管狭窄性疾病易感性的汇总分析

目的 探讨RNF213基因多态性(rs112735431、rs138130613及rs148731719)与颅内血管狭窄性疾病易感性的关联.方法 根据相关数据库,收集涉及RNF213基因多态性与颅内血管狭窄性疾病关联的研究文献,应用Stata 12.0软件选用合适遗传模型,分析异质性并计算合并优势比(odds ratio,OR)及其95％可信区间(confidence interval,口).结果 经筛选共纳入12篇相关文献.汇总分析结果显示,rs112735431多态性与烟雾病易感性在各种遗传模型下均存在显著性关联,其中以显性模型最为显著(AA+ GA基因型对GG基因型:OR 101.46,95％ CI 59.41～173.27;P＜0.001),同时该位点多态性也与非烟雾病性颅内动脉狭窄/闭塞存在显著相关性(AA+ GA基因型对GG基因型:OR 13.82,95％ CI4.48～42.61;P ＜0.001);rs138130613多态性在显性模型下与中国人群烟雾病易感性存在显著性关联(OR 5.01,95％ CI 1.57 ～ 15.98;P =0.006);未发现rs148731719多态性与烟雾病易感性有关联.结论 RNF213基因rs112735431多态性是烟雾病的易感因素,同时该位点多态性还与非烟雾病性颅内动脉狭窄形成有关.系统研究RNF213分子功能对此类血管狭窄性疾病的诊断和治疗具有重要意义.     

Ⅰ型血小板结合蛋白基序解聚蛋白样金属蛋白酶7基因rs3825807位点单核苷酸多态性与冠心病易感性关系的Meta分析

目的:通过系统评价与Meta分析探索Ⅰ型血小板结合蛋白基序的解聚蛋白样金属蛋白酶7(ADAMTS7)基因rs3825807位点单核苷酸的多态性与冠心病发病风险的关联。方法:计算机检索PubMed, Web of Science, Cochrane Library,中国知网,万方,维普和中国生物医学数据库,以获取ADAMTS7基因rs3825807多态性与冠心病易感性的原始研究。检索时限均为建库至2019年12月6日。由两位研究者独立筛选文献、提取数据并评价纳入研究的偏倚风险后,采用RevMan 5.3软件进行Meta分析。结果:共纳入6个病例-对照研究,观察组包括4 989例病例,对照组包含5 471例。Meta分析结果显示,患者ADAMTS7基因rs3825807多态性与冠心病的发病风险增加有相关性(AA vs, GG:OR=21.07,95%CI:1.61～275.95,P=0.02;AG vs. GG:OR=6.80,95%CI:0.77～60.11,P=0.08;AA+AG vs. GG:OR=13.19,95%CI:1.09～158.97,P=0.04;AA vs. AG+GG:OR=2.39,95%CI:1.44～3.96,P=0.0007;A vs. G:OR=23.44,95%CI:8.19～67.10,P0.00001)。结论:患者ADAMTS7基因rs3825807多态性是冠心病的发病风险因素之一。受纳入研究数量和质量限制,本研究需更多的高质量临床研究予以验证。     

钙离子通道β2亚基基因rs4373814位点多态性与东北汉族人群原发性高血压易感性的关联研究

目的:探索钙离子通道β2亚基(CACNB2)基因rs4373814位点的多态性与东北汉族人群(黑龙江省及周边地区)原发性高血压易感性的关联性。方法:采用病例—对照研究方法,在哈尔滨医科大学附属第二医院就诊的患者中收集原发性高血压患者1 006例作为病例组,体检人群中随机选取同期血压正常者992例作为对照组,总计研究人群1 998例。应用Snapshot技术检测CACNB2基因rs4373814位点单核苷酸多态性,利用SPSS 19.0统计学软件进行数据分析处理。结果:CACNB2基因rs4373814位点危险等位基因C的频率分布在病例组和对照组间具有显著性差异[P=0.039,比值比(OR)=1.068,95%可信区间(CI):1.004~1.137]。经Logistic回归校正性别、年龄、BMI、吸烟、饮酒后,发现显性模型CC+GC/GG:增加高血压患病风险(P=0.037,OR=1.260,95%CI:1.013~1.567)。结论 :CACNB2基因rs4373814位点单核苷酸多态性与东北汉族人群原发性高血压的易感性存在显著关联。     

rs12122341多态性与中国汉族人缺血性卒中发病风险无关

目的 探讨rs12122341多态性与中国汉族人群缺血性卒中及其主要亚型的相关性.方法 纳入来自中国汉族人群的缺血性卒中患者和健康对照者,采用改良多重高温连接酶法检测rs12122341基因型.结果 共纳入776例缺血性卒中患者(大动脉粥样硬化性卒中415例,小动脉闭塞性卒中361例)和776例健康对照者.基因分型显示,在所有研究对象中仅检测到rs12122341CC和CG 2种基因型,未检测到GG基因型.病例组等位基因和基因型频率与对照组均无显著性差异.多变量logistic回归分析显示,rs12122341多态性与缺血性卒中[优势比(odds ratio,OR) 1.482,95％可信区间(confidence interval,CI)0.641～3.421;P=0.447]、大动脉粥样硬化性卒中(OR 1.972,95％ CI0.655 ～6.034;P=0.227)和小动脉闭塞性卒中(OR1.632,95％CI0.437 ～6.262;P=1.000)均无显著相关性.结论 在中国汉族人群中,rs12122341多态性与缺血性卒中及其主要亚型均无显著相关性.     

IL-12RB2 rs3790567A/G位点单核苷酸多态性与原发性胆汁性肝硬化易感性的Meta分析

目的评价IL-12RB2 rs3790567A/G位点单核苷酸多态性与原发性胆汁性肝硬化(primary biliary cirrhosis,PBC)易感性的关系。方法通过计算机检索Pub Med、Embase、the Cochrane Library、Web of Science、中国知网、万方等中英文数据库,检索IL-12RB2 rs3790567A/G位点单核苷酸多态性与PBC相关的病例-对照研究。以PBC组与对照组人群基因型频率的OR值和95%CI为效应指标,采用随机或固定效应模型进行定量合并分析,并进行偏倚评估和敏感性分析。采用Rev Man 5. 3软件进行Meta分析。结果本研究共纳入文献6篇,PBC组(病例组) 1 584例,健康对照组2 648名。Meta分析结果表明,IL-12RB2 rs3790567A/G位点与PBC发病因素密切相关。5个基因型结果如下:显性模型:AA+AG vs GG,OR=1. 20,95%CI:1. 11～1. 29,差异有统计学意义(P 0. 05);隐性模型:AA vs AG+GG,OR=1. 59,95%CI:1. 25～2. 02,差异有统计学意义(P 0. 05);共显性模型:AG vs AA,OR=0. 83,95%CI:0. 53～1. 32,差异有统计学意义(P 0. 05); GG vs AA,OR=0. 03,95%CI:0～0. 07,差异有统计学意义(P 0. 05);等位基因模型A vs G,OR=1. 02,95%CI:0. 72～1. 45,差异无统计学意义(P 0. 05)。以研究地理位置及种族不同进行亚组分析,亚洲人显性基因模型:AA+AG vs GG,OR=1. 17,95%CI:0. 89～1. 55,差异无统计学意义(P=0. 26)。高加索人显性基因模型:AA+AG vs GG,OR=1. 30,95%CI:1. 17～1. 44,差异有统计学意义(P 0. 05);亚洲人隐性基因模型AA vs AG+GG,OR=1. 39,95%CI:1. 01～1. 91,差异无统计学意义(P=0. 05)。高加索人隐性基因模型:AA vs AG+GG,OR=1. 94,95%CI:1. 34～2. 81,差异有统计学意义(P 0. 05);亚洲人等位基因模型A vs G:OR=1. 26,95%CI:0. 70～2. 26,P 0. 05,高加索人A vs G,OR=1. 02,95%CI:0. 72～1. 45,差异无统计学意义(P 0. 05)。结论 IL-12RB2 rs3790567A/G在PBC AA和AA+AG基因模型中易感性显著增加,且通过亚组分析,证明种族间差异有统计学意义。     

死亡受体4和5的基因多态性与溃疡性结肠炎易感性的相关性

目的 探讨死亡受体4和死亡受体5基因多态性与UC易感性的关系.方法 收集362例UC患者和490名健康对照者,采用微测序技术(SNaPshot)检测死亡受体4(rs20575,rs13278062)和死亡受体5(rs1047266)3个位点的基因型,采用卡方检验和Fisher确切概率法比较各位点等位基因和基因型频率的分布差异,非条件Logistic回归分析死亡受体4和死亡受体5基因多态性与UC患者临床病理特征的关系.结果 UC组中死亡受体4(rs20575)突变等位基因G和基因型CG+GG的频率高于健康对照组[3.18％(23/724)比1.63％(16/980),x2=4.439,OR=1.977,95％CI:1.037～3.769,P=0.035;6.08％(22/362)比3.27％(16/490),x2 =3.863,OR=1.917,95％CI:0.992～3.705,P=0.049].重度UC患者死亡受体4(rs20575)的突变等位基因G和基因型CG+GG的频率高于轻中度UC患者[8.00％(8/100)比2.40％(15/624),OR=3.530,95％ CI:1.456～8.560,P=0.008;16.00％(8/50)比4.49％(14/312),OR=4.054,95％CI:1.605～10.243,P=0.004].死亡受体4(rs13278062)的突变等位基因和基因型频率在UC组与健康对照组间差异均无统计学意义(P均＞0.05).重度UC患者死亡受体4(rs13278062)的突变等位基因T和基因型GT+TT的频率均低于轻中度UC患者[23.00％(23/100)比36.06％(225/624),OR=0.530,95％CI:0.323～0.868,P=0.011;42.00％(21/50)比61.22％(191/312),OR=0.459,95％CI:0.250～0.841,P=0.010].死亡受体5(rs1047266)突变等位基因和基因型频率在UC组和健康对照组间差异均无统计学意义(P均＞0.05).结论 死亡受体4(rs20575)位点突变等位基因G携带者罹患UC的危险性增加,死亡受体4(rs13278062)基因突变可能影响UC的病情严重程度,而死亡受体5(rs1047266)基因多态性与UC无关联.     

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.