中国人群XRCC1 Arg399Gln基因多态性与肝癌易感性Meta分析

目的:系统评价中国人群X线修复交叉互补基因1(X-ray repair cross complementing group 1,XRCC1)Arg399Gln基因多态性与肝癌易感性的关系.方法:在Pub Med、MEDLINE、EMBASE、CNKI、CBM、VIP及万方数据库中检索2000-01-01/2015-01-10发表的所有有关中国人群XRCC1 Arg399Gln基因多态性与肝癌易感性关系的相关文献.按照纳入和排除标准独立选择文献、提取资料,采用Stata12.0软件进行Meta分析,计算合并比值比(odds ratio,OR)及其95%可信区间(95%confidence interval,95%CI),并进行敏感性分析和发表偏倚的估计.结果:按照入选标准,共纳入13个研究,包括2972例患者和3789例对照者.Meta分析结果显示,与基因型Arg/Arg、Arg/Arg+Arg/Gln分别进行比较,基因型Gln/Gln均增加中国人群罹患肝癌风险(OR=1.47,95%CI:1.24-1.74,P0.001;O R=1.26,95%C I:1.08-1.48,P=0.003);与基因型Arg/Arg进行比较,基因型Gln/Gln+Arg/Gln增加中国人群罹患肝癌风险(OR=1.49,95%CI:1.21-1.83,P0.001).与等位基因Argalele比较,等位基因Gln-allele增加中国人群罹患肝癌的风险(OR=1.33,95%CI:1.16-1.54P0.001).结论:XRCC1 Arg399Gln基因多态性与中国人群肝癌易感性相关,基因型Gln/Gln增加中国人群罹患肝癌的风险.     

DNA修复基因XRCC1 Arg194Trp Arg280His和Arg399Gln多态性与前列腺癌相关性的Meta分析

目的探讨DNA修复基因X线修复交叉互补因子1（XRCC1）主要单核苷酸多态性与前列腺癌易感性的关系。方法在MEDLINE、EMBASE和OVID数据库上检索文献,收集及提取符合纳入标准的以XRCC1密码子194、280、399多态性与前列腺癌易感性为内容的病例对照研究文献,应用Stata统计软件进行Meta分析,比值比（ORs）及其95%可信区间（95%CI）评价关联强度;应用SPSS软件分析吸烟与前列腺癌关系,OR？评价其相对危险度。结果 XRCC1 399 Gln/Gln和XRCC1 280 Arg/His与前列腺癌的发病风险有关（Gln/Gln vs Arg/Arg：OR？=1.27,95%CI=1.02～1.59;Arg/His vs Arg/Arg：OR？=1.66,95%CI=1.09～2.52）,尤其在亚组分析中亚洲人的Gln/Gln明显增加了前列腺癌的发病风险（OR？=1.52,95%CI=1.18～1.96）;Arg194Trp与前列腺癌的发病风险无明显关联。吸烟是前列腺癌的危险因素（χ2=13.974,P=0.000,OR？=1.22）。结论 XRCC1 399 Gln/Gln和280 Arg/His可能与前列腺癌的易感性相关。     

X线损伤交叉互补基因1多态性与结直肠癌易感性研究

目的 探讨DNA修复酶X线损伤交叉互补基因1(XRCC1 )外显子三个位点的基因多态性(Arg194Trp 、Arg280His、Arg399Gln)与结直肠癌(CRC)发病风险的关系.方法 以聚合酶链反应和限制性片段长度多态性(PCR-RFLP)分析方法,采用病例-对照研究,对250例CRC患者(病例组,其中结肠癌128例,直肠癌122例)和213名健康人(对照组)的XRCC1基因三个位点的多态性进行了检测,采用SPSS 11.0软件包统计分析各位点的基因型分布和等位基因频率.结果 XRCC1基因194和399二个位点的各基因型频率在两组间分布差异均无统计学意义(P值均>0.05),但病例组XRCC1基因280 Arg/His基因型频率较对照组显著增高(校正后OR=1.66,95%CI:1.01～2.73,P=0.047).在直肠癌患者组中,280Arg/His基因型频率较对照组显著增高(OR=1.82,95%CI:1.02～3.27),携等位基因280His(Arg280His +His280His)的CRC患者的频率显著高于其在对照组中的频率(校正后OR=1.85,95%CI:1.06～3.22),而在结肠癌患者中风险系数相对较低且差异无统计学意义(校正后OR=1.31,95%CI:0.74～2.35).结论 XRCC1 Arg194Trp和 Arg399Gln基因多态性与结肠癌易感性无关,但280Arg/His基因型能增加CRC易感性,等位基因280His是直肠癌风险因素.

Abstract：

Objective To investigate the correlation between three gene locus polymorphisms of X-ray repair cross-complementary protein 1 (XRCC1) exon (Arg194Trp, Arg280His and Arg399Gln) and the risk of colorectal cancer (CRC). Methods A case-control study was performed in 250 CRC patients (case group, 128 colon cancer patients and 122 rectal cancer patients) and 213 healthy individuals (control group). The three gene locus polymorphism of XRCC1 was tested by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. The genotype distribution and allele frequency of each locus was analyzed with SPSS 10.0 software. Results There was no significant difference in allele frequency of XRCC1 at 194 and 399 loci (P > 0.05). However, the 280 Arg/His allele frequency of XRCC1 was higher in case group than that in control group (OR=1.66,95%CI:1.01~2.73,P=0.047). The 280Arg/His allele frequency was higher in rectal cancer group than that in control group (OR =1.82,95%CI:1.02~3.27). The frequency of 280His allele (Arg280His and His280His) was higher in case group than that in control group (OR=1.85,95%CI:1.06~3.22). However, it was a relative low risk factor of colon cancer and there was no significant difference between colon cancer group and control group (OR=1.85, 95%CI:1.06~3.22). Conclusions There was no correlation between XRCC1 Arg194Trp and Arg399Gln polymorpohisms and the risk of CRC. However, 280Arg/His genotype may increase the risk of CRC, and 280His allele is a risk factor of rectal cancer.     

XRCC1和XPD单核苷酸多态性预测晚期NSCLC铂类化疗敏感性的研究

目的探讨DNA损伤修复基因XRCC1和XPD单核苷酸多态性与晚期非小细胞肺癌(NSCLC)对铂类药物化疗敏感性的关系。方法以聚合酶链反应结合限制性片段长度多态性(PCR-RFLP)方法,检测166例以顺铂(DDP)为基础药物化疗的晚期NSCLC患者XRCC1 Arg194Trp和XPD Asp312Asn多态基因型,并比较不同基因型与化疗敏感性的关系。结果化疗总有效率(CR PR)为31.3%,其中CR2例,PR50例,SD70例,PD44例。携带至少1个XRCC1第194位密码子Trp等位基因患者化疗敏感性是携带Arg/Arg基因型患者的4.3倍(OR=4.32,95%CI=2.10~8.87,P=0.000);携带XPD第312位密码子Asp/Asp基因型患者化疗敏感性是携带至少1个Asn基因型患者的3.5倍(OR=3.49,95%CI=1.76~6.96,P=0.000)。联合分析这两个遗传多态性发现,尚不能认为XRCC1 Arg194Trp和XPD Asp312Asn多态性在NSCLC对铂类药物敏感性中存在联合作用(P>0.05)。结论XRCC1 Arg194Trp和XPD Asp312Asn单核苷酸多态性可能与NSCLC铂类药物敏感性有关。     

XRCC1基因(Arg399Gln)多态性与肝细胞癌易感性关系的Meta分析

目的探讨XRCC1基因(Arg399Gln)多态性与肝细胞癌易感性的关系。方法通过万方、CNKI、Medline、Pub Med、CMB、VIP等公开发表的国内外数据库进行检索,制定检索式对XRCC1基因(Arg399Gln)与肝细胞癌易感性之间关系的研究进行检索。收集2011年至2018年发表的全部相关文献,根据确定的准入标准对文献进行初筛、质量评价、数据提取,同时兼顾文献的权威性、时效性等方面,并通过Rev Man 5. 3软件进行分析。结果最终纳入符合要求文献共9篇,均为病例-对照研究,共计6 671例。其中病例组为3 094例,对照组为3 577例。XRCC1基因表现为AA、A/G、GG型,分别以A为显性基因及A为隐性基因进行对比。分析显示显性基因模型差异无统计学意义(OR=0. 72,95%CI:0. 46～1. 12,P=0. 14),隐性基因模型差异有统计学意义(OR=1. 36,95%CI:1. 01～1. 84,P=0. 04)。结论 A为显性基因模型时XRCC1基因(Arg399Gln)多态性对肝细胞癌的发生、发展无任何作用,A为隐性基因模型时XRCC1基因(Arg399Gln)多态性对肝细胞癌的发生、发展具有促进作用。     

XRCC1和XPD单核苷酸多态性与非小细胞肺癌铂类药物化疗敏感性的关系

目的研究X线修复交叉互补基因1（XRCC1）和着色性干皮病基因（XPD）单核苷酸多态性与老年晚期非小细胞肺癌（NSCLC）铂类药物化疗敏感性关系。方法应用聚合酶链反应结舍限制性片段长度多态性（PCR-RFLP）的方法检测81例以铂类药物为主要化疗方案的NSCLC患者XRCC1 Arg399Gln和XPD Lys751Gin基因型多态性，采用非条件Logistic回归分析不同基因型与化疗疗效的关系。结果81例患者化疗总有效率为35．8％，其中完全缓解（CR）、部分缓解（PR）、稳定（SD）和进展（PD）患者分别为0、29、31、21例。携带至少1个XRCC1 399Arg等位基因的患者化疗敏感性是携带Gln／Gln基因型患者的4.52倍（OR=4．52，95％CI=1.11—18．38）。未发现XPD Lys751Gin遗传多态与化疗敏感性相关。结论XRCC1 Arg399Gln多态可能与晚期NSCLC铂类药物化疗敏感性有关。     

人类XRCC1-399单核苷酸多态性与原发性肝细胞癌的相关研究

目的以病例-对照研究方式探讨人类DNA修复基因XRCC1-399单核苷酸多态性(SNP)与HBV感染者的原发性肝细胞癌(HCC)的发生关系。方法72例HCC患者经病理检查证实,根据地缘、性别、年龄,按1：1～2比例匹配137例非HCC对照者。采用聚合酶链反应一限制片段长度多态性(PCR-RFLP)技术检测受试者XRCC1-399位SNP。结果(1)XRCC1-399SNP和年龄均与HCC的发生无关,但在XRCC1-399Arg／Arg受试者中,HCC的发生与年龄呈负相关(P=0．028);(2)HBV感染是HCC发生的肯定因素(P=0．007);在XRCC1-399Gln／Gln或Arg／Gln受试者中,伴HBV感染者HCC发生率(25．7％)远高于不伴HBV感染者(5．3％,P=0．047);(3)XRCC1-399Arg／Arg受试者HBV感染率与Gln/Gln或Arg／Gln受试者近似(36．6％对38．0％,P=0．052)。结论(1)XRCC1-399Arg／Arg可能具有潜在抵抗HCC发生的作用;(2)XRCC1-399Gln／Gln或Arg／Gln联合HBV感染是HCC发生的高危因素。     

X线交错互补修复基因1多态性与前列腺癌的遗传易感性

选择华东地区207例前列腺癌（PCa）患者为作为病例组,235例非肿瘤、非前列腺疾病的男性患者作为对照组。用PCR-RFLP方法分析两组X线交错互补修复基因1（XRCC1）Arg194Trp和Arg280His两个位点的多态性,比较不同基因型与PCa易感性的关系。结果显示,XRCC1第194密码子携带194Trp等位基因的个体（Arg/Trp＋Trp/Trp）患PCa的风险较Arg/Arg基因型的个体降低38%（校正OR=0.62,95%CI为0.410.93）;在≤70岁及不吸烟两组人群中,携带194Trp等位基因的个体PCa发病风险比Arg/Arg基因型的个体分别降低45%（OR=0.55,95%CI为0.30-1.00）和52%（校正OR=0.48,95%CI为0.24-0.95）。认为XRCC1 Arg194Trp位点多态性可能对PCa遗传易感性产生影响,并与吸烟在PCa的发病中有一定的协同作用。     

晚期NSCLC患者放疗效果与XRCC1 SNP的关系

目的评价晚期非小细胞肺癌(NSCLC)患者放射性治疗疗效及副作用与XRCC1 Codon399单核苷酸多态性的相关性。方法经皮肺穿刺活检病理确诊为鳞癌、腺癌、腺鳞癌或大细胞癌患者60例,以xTAG液相芯片技术检测XRCC1 Codon399的3种基因型。随访至放疗结束后3个月,评价放疗效果和放射性损伤与不同基因型的关系。结果各组在放疗效果方面未发现显著差异。Arg/Gln杂合子组患者发生急性放射性肺损伤的比例高于两组纯合子(P0.05),Arg/Gln和Gln/Gln组患者在消化道损伤方面要高于Arg/Arg纯合子组(P0.05)。在皮肤、食管损伤以及白细胞、血小板等指标未发现显著差异(P0.05)。结论XRCC1 Codon399单核苷酸多态性与NSCLC放疗敏感性无关,但与晚期NSCLC患者肺部及消化道的急性放射性损伤有关,有望成为放射治疗副作用的预测因子之一。     

原发性肝癌患者DNA损伤修复酶基因多态性分析

目的探讨DNA损伤修复酶基因多态性与原发性肝癌发生发展的关系。方法 PCR-RFLP法检测150例肝癌患者（肝癌组）和150例健康体检者（对照组）DNA损伤修复酶基因的表型,并进行比较。结果肝癌组XRCC1 Arg399Gln位点野生型的比率明显低于对照组（P〈0.05）;XRCC1（Arg194Trp、Arg280His）、hOGG1Ser326Cys位点多态性型别在两组中出现的频率相近（P〉0.05）;各基因位点不同表型者的尿8-羟基脱氧鸟苷（8-OHdG）水平相比,P均〉0.05。结论 DNA修复酶基因多态性与肝癌的发生发展无明确的相关关系。     

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.