抗环瓜氨酸多肽抗体检测早期诊断类风湿关节炎研究

目的探讨抗环瓜氨酸多肽（CCP）抗体检测对类风湿关节炎（RA）早期诊断的意义。方法应用ELISA法检测2004-2005年中国医科大学附属盛京医院150份人血清的抗CCP抗体，包括54例RA患者，80例其它风湿病患者，16名正常人；并分析抗CCP抗体与类风湿因子（RF）、C反应蛋白（CRP）、血沉（ESR）的相关性。结果抗CCP抗体对RA的敏感性和特异性分别为70．4％和93．8％。发病2年内与2年以上的抗CCP抗体阳性率差异无显著性。抗CCP抗体阴性组与阳性组的关节畸形率差异无显著性。抗CCP抗体与RF、CRP、ESR无相关性。结论抗CCP抗体对RA具有较好的敏感性和很高的特异性，联合抗CCP抗体和RF可以提高诊断的准确性，对RA的早期诊断具有重要意义。     

类风湿关节炎患者抗环瓜氨酸肽抗体与人类白细胞抗原-DR4等位基因相关性研究

目的 研究类风湿关节炎(RA)及未分类关节炎(痛)(UA)患者抗环瓜氨酸肽(CCP)抗体与人类白细胞抗原(HLA)-DR4等位基因相关性.方法 对91例RA患者,46例UA患者,35名健康志愿者,均为浙江汉族人,应用酶联免疫吸附试验(ELISA)法检测血清抗CCP抗体,序列特异性引物聚合酶链反应(PCR-SSP)检测HLA-DR4等位基因.结果 RA组、UA组HLA-DR4阳性率分别为47.2%、45.6%,均以DRB1*0405为主,分别为25.3%、23.9%.RA组、UA组患者的抗CCP抗体与HLA-DR4具有相关性(r=613,0.703,P＜0.01).与HLA-DRB1*0405具有弱相关性(r=0.304,P＜0.01;r=0.333,P＜0.05). 2组HLA-DR4阳性患者抗CCP抗体水平明显高于HLA-DR4阴性患者,差异有统计学意义(P＜0.01).抗CCP抗体、HLA-DR4均阳性患者红细胞沉降率(ESR)、C反应蛋白(CRP)、血小板水平明显升高,晨僵时间延长,关节肿胀度积分升高,与二者阴性患者比较,差异有统计学意义(P＜0.05或P＜0.01).对UA组患者3个月后随访,抗CCP抗体、HLA-DR4在早期RA的阳性率为94.7%(18/19).结论 抗CCP抗体与HLADR4、DRB1*0405相关;抗CCP抗体、HLA-DR4均阳性反映了RA病情活动性;联合检测抗CCP抗体、HLA-DR4或DRB1*0405有助于RA早期诊断;抗CCP抗体可能在HLA-DR4等遗传因素参与下介导了RA发病.     

RA患者易感基因肽酰基精氨酸脱亚氨酶4mRNA的表达及其意义

目的检测酰基精氨酸脱亚氨酶4（PAD14）在类风湿关节炎（RA）患者外周血单个核细胞（PBMC）mRNA的表达，分析其与RA临床相关指标的相关性，探讨PAD14在RA发病机制中的作用。方法采用反转录聚合酶链反应（RT—PCR）实时荧光定量法对RA组（53例）、骨关节炎（OA）组（27例）及正常对照组（30名）PBMC中PAD14 mRNA表达进行检测，并分析其与抗环瓜氨酸（CCP）抗体、疾病活动关节评分28（DAS28）、患者病程的关系。结果RA组PAD14 mRNA表达明显高于OA组和正常对照组，差异有统计学意义（P〈0．05）；PAD14 mRNA的表达在OA组、正常对照组差异无统计学意义（P〉0．05）。RA组中PAD14 mRNA表达与抗CCP抗体和DAS28评分水平呈明显正相关（r=0．452．0．653，P均〈0．05），与病程呈负相关（r=-0．68，P〈0．05）。结论RA组PAD14 mRNA表达显著增高，并与DAS28评分和抗CCP抗体水平呈明显正相关，与病程呈负相关。提示RA患者PAD14 mRNA表达明显增高，与疾病活动程度和自身免疫功能异常相关。     

抗PADI4抗体检测方法的建立及其在类风湿关节炎中的临床意义

目的检测类风湿关节炎（RA）患者血清中抗肽酰基精氨酸脱亚胺酶4（PADI4）抗体水平，并探讨其在RA中的临床意义。方法选取RA患者109例，系统性红斑狼疮（SEE）患者67例，干燥综合征（pSS）患者48例、系统性硬化症（SSc）患者41例、骨关节炎（OA）患者34例、皮肌炎／多发性肌炎（DM／PM）患者23例、强直性脊柱炎（AS）患者19例，健康对照106名。以重组的人PADI4蛋白为抗原，用酶联免疫吸附法（ELISA）检测患者血清中抗PADI4抗体水平。并研究其与RA患者发病年龄、病程、疾病活动指数DAS28评分、抗环瓜氨酸肽（CCP）抗体、C反应蛋白（CRP）、红细胞沉降率（ESR）、类风湿因子（RF）、免疫球蛋白（IgG、IgM、IgA）、关节x线分期等指标的关系。结果①RA患者血清中抗PADI4抗体的阳性率为45．0％，明显高于其他风湿性疾病患者和健康对照组（P值均〈0．01）。抗PADI4抗体对RA诊断的敏感性为45．0％，特异性为93．5％。②RA患者血清中抗PADI4抗体滴度明显高于其他风湿性疾病患者以及健康对照组（P均〈0．01）。③抗PADI4抗体阳性患者的DAS28评分、抗CCP抗体、ESR、RF、IgG、IgM水平均高于抗PADI4抗体阴性患者（P值均〈0．05）。相关性分析显示抗PADI4抗体水平与DAS28评分（r=0．333，P〈0．01）和抗CCP抗体（r=0．248，P〈0．05）具有相关性。并且阳性组患者出现皮下结节及关节X线Ⅲ期以上改变的比率也明显高于阴性组患者。结论RA患者血清中可以检测到抗PADI4抗体，该抗体在RA中具有很高的特异性，并且与疾病活动及病情严重程度相关，提示PADI4蛋白可能作为自身抗原在RA的发病和病理过程中起重要作用。     

抗Ⅱ型胶原抗体在类风湿关节炎诊断中的意义及口服Ⅱ型胶原对其的影响

目的了解抗Ⅱ型胶原（CU）抗体在类风湿关节炎（RA）中的临床意义及口服鸡CⅡ对血清中抗CⅡ抗体的影响。方法以鸡CⅡ蛋白作为包被抗原，采用酶联免疫吸附试验（ELISA）检测70名健康献血者、113例活动期RA患者，其中病程≤1年的早期患者30例；同时检测19例患者在口服鸡CⅡ90μg，d治疗前和治疗12、24周后血清中的抗CⅡ抗体水平。结果①RA患者血清抗CⅡ抗体水平明显高于健康对照组；RA患者血清抗CⅡ抗体阳性率为37．2％（42／113），正常对照组阳性率为2．9％（2／70），两者比较差异有统计学意义（P〈0．01）；②早期RA患者抗CⅡ抗体阳性率73．3％（22130），而病程〉1年的RA患者抗CⅡ抗体阳性率为24．1％（20／83），两组差异具有统计学意义（P〈0．05）；③比较抗CⅡ抗体阳性组和阴性组其他相关指标：抗CⅡ抗体阳性组42例，阴性组71例，两组类风湿因子（RF）阳性率分别为83．3％（35／42）和43．7％（31／71），两组比较差异有统计学意义（P〈0．05）；抗环瓜氨酸肽（CCP）抗体阳性率分别为90．5％（38／42）和52．1％（37／71），两组比较差异有统计学意义（P〈0．05）：同时抗CⅡ抗体阳性组的血沉（ESR）、C反应蛋白（CRP）水平均高于抗CⅡ抗体阴性组；两组在日常生活能力及骨质破坏方面差异无统计学意义；④口服CⅡ治疗前和治疗12、24周后，RA患者血清抗CⅡ抗体水平有逐渐下降趋势，但差异无统计学意义。结论RA患者抗CⅡ抗体明显升高，尤其在早期RA患者有较高的阳性率：抗CⅡ抗体阳性患者RF、抗CCP抗体阳性率明显高于阴性患者，同时ESR、CRP亦明显升高；口服CⅡ治疗后抗体水平有逐渐下降趋势。因此，抗CⅡ抗体在RA发病中可能起着重要的作用，可作为早期诊断、判断病情活动的指标之一；口服CⅡ对CⅡ抗体的影响有待进一步观察。     

抗环瓜氨酸肽抗体和葡萄糖-6-磷酸-异构酶抗原对类风湿关节炎诊断价值的比较

目的评价抗环瓜氨酸肽（CCP）抗体和葡萄糖-6-磷酸-异构酶（GPI）抗原对类风湿关节炎（RA）的诊断价值。方法用酶联免疫吸附试验（ELISA）法分别测定RA患者112例、非RA其他风湿病患者44例以及健康志愿者119名血清中的抗CCP抗体、GPI抗原和IgM—RF，应用ROC比较抗CCP抗体和GPI抗原对RA的诊断价值，用Spearman方法分析上述指标与lgM—RF的相关性。结果在诊断RA时．抗CCP抗体和GPI抗原的ROC曲线下面积均大于IgM—RF（P均〈0．05）。抗CCP抗体、GPI抗原与IgM—RF显著相关。CCP抗体与GPI抗原的联合试验的灵敏度达到0．946。结论联合测定抗CCP抗体和GPI抗原对RA具有较高的诊断价值，具有良好的应用前景。     

类风湿关节炎患者抗CCP抗体检测及与其他实验室指标的关系

目的探讨抗环瓜氨酸肽抗体（抗CCP抗体）在类风湿关节炎（RA）中的诊断价值。方法选择RA患者116例、其他自身免疫病患者79例、健康对照者50例,采用ELISA法行抗CCP抗体检测,并检测RA患者的相关实验室指标。结果抗CCP抗体诊断特异性（94.58%）高于类风湿因子（RF）（68.22%）。进行抗CCP抗体、RF联合检测时,以任一项指标阳性的敏感性高于两者均阳性的敏感性（P〈0.05）。抗CCP抗体阳性的RA患者C反应蛋白（CRP）、血沉（ESR）均高于阴性者（P〈0.01）。结论抗CCP抗体在RA诊断中具有较高特异性,以抗CCP抗体或RF任一种阳性为诊断指标有利于早期诊断RA。抗CCP抗体阳性可能与RA活动性相关。     

抗环瓜氨酸多肽抗体检测早期诊断类风湿关节炎研究

目的探讨抗环瓜氨酸多肽(CCP)抗体检测对类风湿关节炎(RA)早期诊断的意义。方法应用ELISA法检测2004—2005年中国医科大学附属盛京医院150份人血清的抗CCP抗体,包括54例RA患者,80例其它风湿病患者,16名正常人;并分析抗CCP抗体与类风湿因子(RF)、C反应蛋白(CRP)、血沉(ESR)的相关性。结果抗CCP抗体对RA的敏感性和特异性分别为70·4%和93·8%。发病2年内与2年以上的抗CCP抗体阳性率差异无显著性。抗CCP抗体阴性组与阳性组的关节畸形率差异无显著性。抗CCP抗体与RF、CRP、ESR无相关性。结论抗CCP抗体对RA具有较好的敏感性和很高的特异性,联合抗CCP抗体和RF可以提高诊断的准确性,对RA的早期诊断具有重要意义。     

抗CB10抗体在类风湿关节炎患者中的意义

目的检测抗Ⅱ型胶原抗原表位的多肽片段（GPAGTAGAR）抗体，即抗CB10抗体在类风湿关节炎（RA）中的阳性率，探讨抗CB10抗体在RA中的意义。方法以人工合成CB10多肽为抗原，用酶联免疫吸附试验（ELISA）检测164例RA、40例系统性红斑狼疮（SLE）、55例骨关节炎（OA）、66例强直性脊柱炎（AS）、63名正常人血清及19例RA和14例AS关节液中抗CB10抗体的水平。分析比较各组抗CB10抗体的水平及其与临床资料的关系。结果RA患者血清中抗CB10抗体的吸光度（A）值水平明显高于其他风湿病组和正常对照组，差异有统计学意义（P〈0．01），其在RA、SLE、AS、OA及正常对照组中的阳性率分别为：71．3％、12．5％、30．3％、12、7％和3．2％，对RA的敏感性为71．3％，特异性为82．1％；阳性预测值为77．5％，阴性预测值为80．2％。病程≤2年的RA患者抗CB10抗体阳性率明显高于病程〉2年者，差异有统计学意义（P〈0．05）。抗CB10抗体与病程及x线分期呈负相关（P〈0．05），与关节压痛数、关节肿胀数、晨僵、休息痛、健康评价问卷（HAQ）、类风湿因子（RF）、抗环瓜氨酸肽（CCP）抗体、红细胞沉降率（ESR）等指标无明显相关性。结论RA患者血清中抗CB10抗体明显升高，对RA诊断有较好的敏感性和特异性：抗CB10抗体与病程及x线分期呈负相关。     

抗CCP抗体和抗Sa抗体联合检测对老年人RA的临床意义

目的探讨抗环瓜氨酸肽抗体（抗CCP抗体）和抗Sa抗体联合检测对老年人类风湿关节炎（RA）的临床意义。方法检测85例老年人RA患者的抗CCP抗体和抗Sa抗体,结合临床资料分析。结果抗CCP抗体和抗Sa抗体对RA诊断敏感性分别为77．6％和32．9％,特异性分别为97．4％和95．4％。抗CCP抗体、抗Sa抗体、类风湿因子（RF）均阳性组医生对病情评估、患者对病情评估、Sharp评分、ESR及CRP水平均较阴性组增高。24例RF阴性老年人RA中,抗CCP抗体、抗Sa抗体阳性率分别为50％、41．7％。结论抗CCP抗体和抗Sa抗体联合检测有助于老年人RA的诊断,且二者与患者病情活动性及严重性相关。     

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.     

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.     

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.     

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.