CTLA-4基因外显子1A/G49多态性与1型糖尿病的相关性研究

目的 探讨细胞毒性T淋巴细胞相关抗原4（CTLA－4）基因外显子1的49位点A／G多态性与中国汉族人1型糖尿病（DM）的关系。方法 采用多聚酶链式反应限制性片段长度多态性（PCR－RFLP）技术对33例典型1型DM患者、57例成人晚发自身免疫性糖尿病患者（LADA)和84例健康对照者分析CTLA－4基因外显子1的49位点基因型。结果 1型DM患者的CTLA－4／G^49等位基因频率显著高于对照组（P=0.0005)，而典型1型DM和LADA两组间无显著性差异（P＝0.097)；ICA和GADAb阳性率与G^49无明显相关性（分别为P＝0.065,P=0.066)。结论 CTLA－4基因外显子1多态性与中国汉族人1型DM有关，G^49等位基因是1型DM的独立危险因素之一。     

细胞毒性T淋巴细胞相关抗原4/CT60基因多态性与溃疡性结肠炎的关系

目的探讨细胞毒性T淋巴细胞相关抗原4（CTLA4）CT00位点基因多态性与中国湖北地区汉族人溃疡性结肠炎（UC）的相关性。方法共收集64例UC患者和109例正常对照静脉血标本提取基因组DNA。采用多聚酶链反应．限制性片段长度多态性分析（PCR-RFLP）方法检测CT60G／A（rs3087243）位点的多态性，计算CTLA4的基因型和等位基因频率。结果CT60G／A基因型分布及等位基因频率，UC组与正常对照组比较差异无显著性，中国湖北地区汉族人群CTLA4CT60基因型和等位基因分布与日本人群相似。而与西班牙人群分布存在显著差异。结论CT60基因多态性与中国湖北汉族人UC易感性无关。     

CTLA—4与1型糖尿病

细胞毒T淋巴细胞相关抗原－4（CTLA－4）是T细胞增殖、活化的负调控因子,在诱导自身耐受过程中起主要作用。1型糖尿病（DM）是T细胞介导的自身免疫性疾病,部分1型DM的发生可能与CTLA－4的表达及功能缺陷有关。多种族研究证实CTLA－4基因第1外显子49位点等位基因G与1型DM易感性关联。     

内皮细胞型NO合酶基因第7外显子894G→T点突变与糖尿病肾病相关性研究

目的 探讨内皮细胞型NO合酶（eNOS)基因第7外显子894G→T点突变与中国北方汉族人2型糖尿病（T2DM）合并肾病（DN）之间的关系。方法 运用聚合酶链式反应限制性片段长度多态性技术（PCR－RFLP），结合DNA测序技术，检测了228例中国北方汉族人的eNOS基因第7外显子894G→T错义突变位点的基因型，其中T2DM患者143例（DN79例），健康成人85例，并对各组间的等位基因频率与基因型频率进行了比较。结果 ①T2DM组的T等位基因及TG基因型频率与正常对照（N）组无显著性差异（P＞0．05）。②DN＋组T等位基因及TG基因型频率显著高于糖尿病非肾病患者（P＜0．05）。③SBP、HbA1c、TC、TG和eNOS基因第7外显子894G→T点突变均与糖尿病肾病有关（P＜0．05）。结论 eNOS基因第7外显子894G→T点突变的T等位基因可能是中国人2型糖尿病易患肾病的独立危险因素。     

斑秃与CTLA-4基因外显子1 A/G49多态性研究

目的探讨细胞毒性T淋巴细胞相关抗原4（CTLA-4）基因外显子1第49位点A/G多态性是否与斑秃的遗传易感性有关。方法采用聚合酶链反应-限制性片段长度多态性分析（PCR-RFLP）对56例斑秃患者和124例正常对照者的CTLA-4基因外显子1的第49位点进行基因分型。结果斑秃患者CTLA-4基因第一外显子第49位点基因型频率与正常对照组比较差异无统计学意义（χ^2=1.768,P〉0.05）;斑秃患者CTLA-4基因第一外显子第49位点等位基因频率与正常对照组比较差异无统计学意义（χ^2=1.676,P〉0.05）。结论CTLA-4基因第一外显子第49位碱基A→G多态性与斑秃的发病可能无相关性。     

2010～2014年青海省高原地区甲状腺眼病和CTLA-4基因多态性的相关性研究调查

目的 探讨2010~2014年青海省高原地区甲状腺眼病患者CTLA-4基因多态性与疾病的关联。方法 选取西宁地区12所医院收治的72例Graves病患者,将其中合并有甲状腺眼病的31例患者作为试验A组,其余41例单纯Graves病患者作为试验B组,另选取40例同年龄段正常健康人群作为对照组。所有研究对象均取全血对CTLA-4基因启动因子-318位、CT60位和外显子1+49位基因型分布和等位基因频率进行检测对比,分析上述位点基因多态性和等位基因频率分别和高原地区甲状腺眼病关联。结果 三组研究对象CTLA-4基因-318位基因型分布比较,差异无统计学意义(P>0.05),而CT60位点和外显子1+49位点基因型分布比较差异有统计学意义(P<0.05),其中每两组间差异均有统计学意义(P<0.05);甲状腺眼病和CTLA-4基因启动因子-318位点等位基因频率无明显关联,和CT60位点A和外显子1+49位点A基因频率存在显著负向关联,而和两位点G基因频率均存在明显正向关联。结论高原地区甲状腺眼病和CTLA-4基因CT60位点和外显子1+49位点多态性均存在明显关联,A等位基因频率降低,G等位基因频率升高,甲状腺眼病患病风险增加。     

中国人CTLA-4基因外显子1多态性与Graves病的相关性

以PCR RFLP技术观察 2 8名健康人与 64例Graves病 (GD)患者细胞毒性T淋巴细胞相关抗原 4(CTLA 4)基因外显子 1的多态性 ,结果提示GD患者的CTLA 4外显子 1的G49等位基因频率较正常对照组高 (P <0 .0 5 ) ,CTLA 4基因可能是GD的一个新的易感候选基因。     

Calpain 1 O基因多态性与中国人2型糖尿病遗传易感性的相关性研究

目的 了解Calpain 10基因对中国汉族人2型糖尿病遗传易感性的影响。方法 采用病例对照研究方法：以聚合酶链式反应－限制性内切酶长度多态性（PCR－RFLP）技术，对211例2型糖尿病患者及127例正常对照Calpain 10基因SNP43及SNP19多态性进行基因分型。结果 同对照组相比，SNP43的G等位基因频率在2型糖尿病人群中显著升高（91．9％ vs 85.8%,P=0.01)。但SNP19位点等位基因频率在上述两组中的频率分布无显著差异。此外，本研究还观察到在正常对照组中，SNP43GG基因型与体重指数和腰－臂围比值增加相关。结论 Calpain 10基因SNP43位点G等位基因可直接或与其他糖尿病基因相互作用决定汉族人2型糖尿病的遗传易感性。     

CTLA-4基因多态性与中国南方汉族人Graves病的相关性

用PCR-RFLP和PCR．SSLP分别确定CTLA-4基因第1外显子49位点基因型和第4外显子3，末端AT重复序列的基因型，分析广东汉族120例Graves病患者及123名正常对照组CTLA-4基因多态性。结果显示CTLA-4基因外显子1A49G及外显子4（AT）n多态性与广东汉族人GD不相关。     

脂联素基因多态性与2型糖尿病的相关性研究

目的探讨脂联素基因（apM1）2号外显子＋45位点T/G多态性与滨州地区汉族人群2型糖尿病（T2DM）的关系。方法采用聚合酶链反应—限制性片段长度多态性方法 ,检测100例T2DM患者及100例健康者的apM1 2号外显子＋45位点T/G多态性。结果与健康者比较,T2DM患者G/G基因型分布、G等位基因频率明显升高,T等位基因频率明显降低（P均〈0.01）。结论 apM1可能是滨州地区汉族人群T2DM的易感基因。     

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.     

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.     

N-acetyl-L-cysteine combined with mesalamine in the treatment of ulcerative colitis： Randomized,placebo-controlled pilot study

AIM： To evaluate the effectiveness and safety of oral N-acetyl-L-cysteine （NAC） co-administration with mesalamine in ulcerative colitis （UC） patients.
METHODS： Thirty seven patients with mild to moderate UC were randomized to receive a four-wk course of oral mesalamine （2.4 g/d） plus N-acetyl-L-cysteine （0.8 g/d） （group A） or mesalamine plus placebo （group B）. Patients were monitored using the Modified Truelove-Witts Severity Index （MTWSI）. The primary endpoint was clinical remission （MTWSI ≤ 2） at 4 wk. Secondary endpoints were clinical response （defined as a reduction from baseline in the MTWSI of ≥ 2 points） and drug safety. The serum TNF-α, interleukin-6, interleukin-8 and MCP-1 were evaluated at baseline and at 4 wk of treatment. RESULTS： Analysis per-protocol criteria showed clinical remission rates of 63% and 50% after 4 wk treatment with mesalamine plus N-acetyl-L-cysteine （group A） and mesalamine plus placebo （group B） respectively （OR = 1.71; 95% CI： 0.46 to 6.36; P = 0.19; NNT = 7.7）. Analysis of variance （ANOVA） of data indicated a significant reduction of MTWSI in group A （P = 0.046） with respect to basal condition without significant changes in the group B （P = 0.735） during treatment. Clinical responses were 66% （group A） vs 44% （group B） after 4 wk of treatment （OR = 2.5; 95% CI： 0.64 to 9.65; P = 0.11; NNT = 4.5）. Clinical improvement in group A correlated with a decrease of IL-8 and MCP-1. Rates of adverse events did not differ significantly between both groups.
CONCLUSION： In group A （oral NAC combined with mesalamine） contrarily to group B （mesalamine alone）, the clinical improvement correlates with a decrease of chemokines such as MCP-1 and IL-8. NAC addition not produced any side effects.     

Delorme's transrectal excision for internal rectal prolapse

Surgical therapy of functional outlet obstruction in patients with internal rectal intussusception may include abdominal, perineal, or transrectal procedures. Because abdominal procedures often result in significant physiologic impact but unrelieved constipation, the authors have elected Delorme's transrectal excision for management of these patients. Since a short-term placebo effect attends many therapies, this report describes results of transrectal excision only after a threeyear postoperative period. Delorme's transrectal excision of internal intussusception accomplished sustained symptomatic relief in over 70 percent of otherwise refractory constipated patients. The association of internal intussusception with other abnormalities underscores the importance of defining both anatomic and functional components when selecting patients whose constipation may require surgical therapy. Critical technical elements, surgical pitfalls, and potential complications of the procedure are discussed.Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Toronto, Canada, June 11 to 16, 1989.