广西壮族人Caveolin-3基因多态性与2型糖尿病的关系

目的探讨广西壮族人Caveolin-3基因外显子单核苷酸多态性（SNP）与2型糖尿病（T2DM）的关系。方法选择24例T2DM（T2DM组）患者及10例正常对照者（对照组）,应用PCR法对两组广西壮族人Caveolin-3基因外显子SNP进行PCR扩增后测序。结果 Caveolin-3基因第2外显子非编码区有2个位点发生突变,分别是12842 A→G和12715 A→T。2位点的等位基因频率在糖尿病组和正常对照组存在统计学差异（P〈0.05）。12842A→G和12715 A→T位点有三种联合基因型（AT、GT、GA）,其中AT、GA型的分布频率在两组中比较P〈0.05。结论 Caveolin-3基因12842 A→G和12715 A→T位点突变可能与T2DM的发病有关。     

蛋白酪氨酸磷酸酶1B基因多态性与2型糖尿病和肥胖的相关性研究

目的 研究中国人群中蛋白酪氨酸磷酸酶1B（PTP-1B）基因的单核苷酸多态性（SNP）与2型糖尿病及肥胖的相关性。方法 采用直接测序法对PTP—1B基因作SNP筛查，并在夫妻配对样本中对所检出的SNP作基因分型。结果 共检出6个SNPs位点，其中内含子区3个（15／37C→A，16／82A→G，17／301C→T），外显子区3个（E8／45C→T，E9／35G→A，E10／372G→A），其中E9／35G→A为新发现的突变类型；在病例-配偶对照研究中发现，15／37C→A，16／82A→G和17／301C→T等位基因频率在糖尿病患者和正常人配偶中差异有统计学意义（均P〈0．05），其余位点的等位基因频率在两组间的分布则无明显差异。与肥胖的相关性研究中发现15／37C→A和17／301C→T位点与男性的腰臀比（WHR）相关（P〈0．05）。结论 PTP-1B基因的SNP位点15／37C→A，16／82A→G和17／301C→T多态性可能和2型糖尿病的发病相关，其中15／37C→A和17／301C→T与男性的WHR相关。     

解偶联蛋白与肥胖及2型糖尿病

解偶联蛋白 (UCPs)能将呼吸链与ATP产生过程解偶联而影响体内能量平衡。UCPs的表达受到甲状腺素、糖皮质激素、β3 肾上腺能激动剂、Leptin等调节。 2型糖尿病患者骨骼肌中UCP3mRNA特异性降低 ,UCP3基因外显子 6号连接区突变引起脂肪氧化减少和高呼吸商 ,内含子 4号C→T突变与肥胖的糖尿病发生相关联 ,提示UCP3基因的变异在肥胖和 2型糖尿病的病因中起一定作用。     

2型糖尿病与簇蛋白基因关联的初步研究

目的探讨2型糖尿病（T2DM）与簇蛋白（Glu）基因多态性的关联。方法聚合酶链式反应-变性梯度凝胶电泳（PCR-DGGE）和DNA测序技术分析62例T2DM患者及60例正常对照者的Glu基因外显子2和外显子5基因多态性。结果Glu基因外显子2发现1个多态位点：1963（＋A）;外显子5发现3个多态位点：（1）7476（-A）,（2）7534（-C）,（3）7521C→T。结论Glu基因外显子2和外显子5多态性在2型糖尿病组和正常对照组多态性位点基因频率分布差异有统计学意义。因此,Clu基因外显子2和外显子5多态性可能与T2DM易感性有关联。     

2型糖尿病患者肾素血管紧张素Ⅱ1型受体基因多态性与瘦素、白介素6的相关性

目的 分析2型糖尿病患者肾素血管紧张素Ⅱ1型受体基因(AGTR1)A10208G位点多态性与瘦素(LEP)、白介素6(IL-6)的关系. 方法 PCR-RFLP法检测105例伴有肥胖的2型糖尿病患者(DM-O组)、22例不伴肥胖的2型糖尿病患者(DM-N组)及224例健康人(NC组)AGTR1基因A10208G位点多态性,并测定相应指标进行分析. 结果 (1)DM-O组AG+GG基因型分布和等位基因频率显著高于NC组;(2)DM-O组、DM-N组携A等位基因患者LEP显著高于携G患者. 结论 AGTR1基因A10208G位点多态性与伴有腹型肥胖的2型糖尿病存在相关性;LEP抵抗可能是未发生AGTR1基因A10208G位点A→G突变的2型糖尿病重要发病因素之一.     

UCP1基因-3826A>G位点多态性与云南大理地区2型糖尿病患病率相关性的研究

目的 探讨解偶联蛋白1(UCP1)基因-3826 A>G位点多态性与云南大理地区T2DM患病率的相关性。方法 选取2021年1～12月于大理大学第一附属医院内分泌科收治的204例T2DM患者（T2DM组），同期选取174名体检健康者为正常对照（NC）组，收集两组一般资料和生化指标，采用竞争性等位基因特异性PCR(KASP)对UCP1基因-3826 A>G位点进行基因分型并统计分析。结果 T2DM、NC组UCP1基因-3826 A>G位点基因型均符合Hardy-Weinberg遗传平衡（P>0.05）。T2DM组AG、GG基因型频率和G等位基因频率高于NC组。AG、GG基因型和G等位基因可增加T2DM风险1.638、2.109和1.386倍。T2DM患者AG和GG基因型BMI高于AA基因型（P<0.05）。结论 UCP1基因-3826 A>G位点多态性与云南大理地区T2DM相关，且该基因位点突变增加T2DM风险。     

脂蛋白脂肪酶内含子3C→T突变

为筛查中国人群脂蛋白脂肪酶基因的突变情况，并探讨这些突变对脂蛋白代谢可能产生的影响，研究者利用聚合酶链反应一单链构象多态性分析技术，对140例人群(高甘油三酯血症组51例，正常对照组89例)的脂蛋白脂肪酶基因进行了突变筛查，对可疑突变的扩增样品进行DNA序列测定。结果在外显子4扩增片段(包括内含子--外显子交界区)有2例可疑突变被检出，经测序证实均为内含子3受位剪接住点上游6bp的C→T转换突变杂合子。由于该突变仅见于重度高甘油三酯血症患者，结合国内外相关文献，研究者认为我国人群存在脂蛋白脂肪酶基因内含子3受位剪接位点的C→T突变，该突变可能是我国人群高甘油三酯血症的遗传易患因子。     

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。     

Pax6基因的Arg67Arg与Thr166Thr突变致胰岛素分泌减少所致糖代谢异常与早发2型糖尿病的相关性研究

目的探讨Pax6基因的Arg67Arg与Thr166Thr突变致早发T2DM的临床特点。方法选取早发T2DM患者112例(T2DM组)和OGTT正常者98名(NGT组),采用聚合酶链式反应(PCR)测定两组Pax6基因突变/变异情况,比较FPG、2hPG、FIns等指标。结果 T2DM组检出Pax6基因外显子6的Arg67Arg(A→G)突变,突变型等位基因G和野生型A基因频率分别为2.23%和97.77%,未检出Pax6基因外显子7的Thr166Thr(T→C)突变;NGT组未检测到Pax6基因Arg67Arg和Thr166Thr突变;AG基因型患者FPG和2hPG水平高于AA基因型患者,而FC-P、2hC-P、FIns和2hIns水平低于AA基因型患者(P0.05)。结论Pax6基因的Arg67Arg与Thr166Thr突变可能不是人群早发T2DM的易感标志,但Arg67Arg突变可加剧胰岛素分泌的减少。     

线粒体DNA3537A→G、4824A→G、5351A→G突变与2型糖尿病的相关性研究

目的研究T2DM患者线粒体ND1基因3537A→G和ND2基因4824A→G、5351A→G突变与T2DM的相关性。方法应用PCR-RFLP技术检测145例T2DM和334例正常对照者（NC）线粒体DNA（mtDNA）3537A→G、4824A→G、5351A→G突变情况。结果NC组mtDNA4824A→G突变率高于T2DM组（P＜0．05）。3537A→G及5351A→G突变率在两组中无统计学差异（P〉0．05）。结论mtDNA4824A→G突变可能为T2DM患病的保护因素。3537A→G及5351A→G突变可能与T2DM不相关。     

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.