超声多普勒引导下痔动脉结扎加悬吊术治疗痔14例疗效观察

为观察超声多普勒引导下痔动脉结扎加悬吊术治疗痔的临床疗效及安全性,我们运用痔动脉超声多普勒诊断仪治疗痔患者14例,其中混合痔5例,Ⅰ期内痔3例,Ⅱ期内痔3例,Ⅲ期内痔3例。随访半年,13例患者症状全部消失,1例患者肛门有小皮赘脱出,但无不适感,总有效率100％。术中术后患者基本无疼痛感。结果表明,超声多普勒引导下痔动脉结扎加悬吊术治疗痔安全、有效、疼痛轻、并发症少。     

腹腔镜下幽门环肌切开术治疗小儿先天性肥厚性幽门狭窄50例报告

目的总结腹腔镜下幽门环肌切开术治疗小儿先天性肥厚性幽门狭窄的成功经验.方法2001年4月～2004年4月,应用腹腔镜下幽门环肌切开术治疗小儿先天性肥厚性幽门狭窄50例,年龄12～90 d,平均35 d.分别在左、右上腹各置入3 mm trocar,左侧trocar置入无损伤抓钳夹近幽门处胃壁,右侧trocar先后置入伸缩式幽门肌切开刀、剥离器和幽门分离钳,完成幽门环肌切开术.结果腹腔镜下完成手术48例,中转开腹2例,其中1例为术中发现幽门前瓣膜症,1例为幽门黏膜损伤,经开腹修补痊愈.手术时间15～45 min,平均25 min.术后6 h拔胃管,开始喂奶.3～5 d出院.42例术后随访3～6个月,平均4.5月,生长发育均恢复正常.结论丰富的开腹手术经验、熟练的腹腔镜操作技术、术中良好的麻醉和合适的手术器械是完成腹腔镜下幽门环肌切开术的保障.     

骨髓基质干细胞修复兔关节软骨缺损的实验研究

目的研究以多聚乙醇酸(PGA)为支架的骨髓基质干细胞(BMSCs)复合物修复兔膝关节软骨缺损的情况。方法体外培养扩增的自体BMSCs种植于PGA支架并培养72h,然后将支架-细胞复合物植入兔关节软骨缺损模型。术后12周处死动物,标本行大体观察、组织学检查及Ⅱ型胶原免疫组化染色。结果BMSCs-PGA复合物植入后形成丰富的透明软骨样修复组织,新生软骨无明显退变。对照组主要为纤维组织及软骨下骨修复。结论BMSCs-PGA复合物可修复关节软骨缺损。     

生长因子FGF在颅缝细胞培养中作用的研究

目的:研究生长因子FGF在颅缝闭合中的调控作用.方法:以颅缝早闭动物模型(SD鼠)的颅缝为研究模型,采用细胞生物学技术、组织化学技术,研究颅缝闭合期间,生长因子bFGF作用下,细胞胶原及骨钙素分泌情况;观察生长因子bFGF,对分离培养的颅缝细胞增殖与代谢影响.结果:在大鼠颅缝分离培养细胞中,bFGF促进颅缝分离培养细胞分泌胶原、骨钙素,加快细胞增殖生长曲线平台期出现,并有效促进大鼠颅缝分离培养细胞S期增殖(p＜0.05).结论:在体外器官培养中,bFGF能促进大鼠分离培养颅缝细胞的活性(p＜0.05).     

BMP7腺病毒基因转染对骨髓基质干细胞生物学的影响

目的 探讨BMP7腺病毒基因转染对骨髓基质干细胞(BMSCs)的体外、体内的生物学功能影响.方法 抽取羊的骨髓,分离、培养骨髓基质干细胞.用重组骨形成蛋白7腺病毒(adenovirus bone morphogenetic protein 7;Adeno-BMP7)转染(M.O.I=100)70%～80%融合时的第二代细胞,三天后分别进行透射电镜观察、流式细胞仪检测、Western-blot、钙结节染色以及珊瑚和细胞复合物皮下回植.结果 在体外:细胞超微结构观察显示Adeno-BMP7基因转染后的BMSCs的物质合成代谢功能活跃;流式细胞仪检测表明Adeno-BMP7基因转染对BMSCs的细胞周期无明显影响;Western-blot检测证明转染Adeno-BMP7后的BMSCs有BMP7在蛋白水平上的表达;染色表明转染Adeno-BMP7后的BMSCs可形成较大的钙结节.在体内:转染Adeno-BMP7的BMSCs可明显促进新骨的形成,与没转染Adeno-BMP7的BMSCs有差异.结论 Adeno-BMP7转染可促进BMSCs的体外成骨定向分化,Adeno-BMP7转染后的BMSCs具有更强的体内成骨能力.     

阴道粘膜上皮细胞的分离培养和鉴定

目的 初步建立阴道粘膜上皮细胞体外培养方法,为阴道粘膜上皮研究提供实验模型.方法 取雌性新西兰大白兔阴道粘膜组织小块,胶原酶Ⅳ和胰蛋白酶联合消化分离法收集上皮细胞,接种于角朊细胞无血清培养液中静置培养、传代.动态观察细胞生长增殖情况,扫描和透射电镜观察超微结构,流式细胞仪测定细胞增殖周期,并进行免疫组织化学鉴定.结果 体外培养的阴道粘膜上皮细胞为二倍体细胞,增殖状态良好,细胞间可见桥粒连接,免疫组化角蛋白染色阳性.细胞的超微结构和免疫组化染色均具有上皮细胞特征.结论 在本实验条件下,体外培养的阴道粘膜上皮细胞具有较好的增殖能力,可作为阴道粘膜上皮研究的理想实验模型.     

草酸钙结石形成对肾组织bikunin和IαI表达的影响

目的研究肾草酸钙结石形成对肾组织bikunin基因和间α胰蛋白酶抑制物(IαI)蛋白表达的影响,探讨bikunin在尿结石形成中的意义。方法诱导实验性大鼠肾草酸钙结石模型,收集结石大鼠、正常大鼠、临床肾结石和非结石患者每组各8例的肾组织标本。采用免疫组化、逆转录聚合酶链反应(RT-PCR)和计算机图像分析技术分别检测所有大鼠和人肾组织中bikuninmRNA和IαI蛋白的表达水平。结果正常大鼠和非结石患者肾组织均存在bikuninmRNA和IαI蛋白的表达。肾草酸钙结石形成后,结石大鼠肾组织IαI蛋白的灰度值和bikuninmRNA的相对表达水平分别为198.43±15.17、0.70±0.14;肾结石患者肾组织IαI蛋白的灰度值和bikuninmRNA的相对表达水平分别为263.25±17.41、1.27±0.13,分别和对照组相比,均显著增加(P<0.05)。结论Bikunin作为构成IαI的轻链结构,在肾草酸钙结石形成后,bikuninmRNA的表达迅速增强,提示机体通过肾脏合成更多的bikunin来抑制肾草酸钙结石的形成。     

Expression of a novel beta adaptin subunit mRNA splice variant in human testes

中央驻青单位在西宁海关学习交流经验,海东大力培训农村实用人才,海西州提高干部考核质量,海北州分析评议做到“五个结合”,海南州干部人事制度改革成效显著,西宁市城北区优化村党支部班子结构,乐都县先进性教育与办实事相结合,门源县先进性教育促民族团结,河南县先进性教育重落实。     

Glucagon-Like Peptide 1/Glucagon Receptor Dual Agonism Reverses Obesity in Mice

OBJECTIVE

Oxyntomodulin (OXM) is a glucagon-like peptide 1 (GLP-1) receptor (GLP1R)/glucagon receptor (GCGR) dual agonist peptide that reduces body weight in obese subjects through increased energy expenditure and decreased energy intake. The metabolic effects of OXM have been attributed primarily to GLP1R agonism. We examined whether a long acting GLP1R/GCGR dual agonist peptide exerts metabolic effects in diet-induced obese mice that are distinct from those obtained with a GLP1R-selective agonist.

RESEARCH DESIGN AND METHODS

We developed a protease-resistant dual GLP1R/GCGR agonist, DualAG, and a corresponding GLP1R-selective agonist, GLPAG, matched for GLP1R agonist potency and pharmacokinetics. The metabolic effects of these two peptides with respect to weight loss, caloric reduction, glucose control, and lipid lowering, were compared upon chronic dosing in diet-induced obese (DIO) mice. Acute studies in DIO mice revealed metabolic pathways that were modulated independent of weight loss. Studies in Glp1r^−/− and Gcgr^−/− mice enabled delineation of the contribution of GLP1R versus GCGR activation to the pharmacology of DualAG.

RESULTS

Peptide DualAG exhibits superior weight loss, lipid-lowering activity, and antihyperglycemic efficacy comparable to GLPAG. Improvements in plasma metabolic parameters including insulin, leptin, and adiponectin were more pronounced upon chronic treatment with DualAG than with GLPAG. Dual receptor agonism also increased fatty acid oxidation and reduced hepatic steatosis in DIO mice. The antiobesity effects of DualAG require activation of both GLP1R and GCGR.

CONCLUSIONS

Sustained GLP1R/GCGR dual agonism reverses obesity in DIO mice and is a novel therapeutic approach to the treatment of obesity.Obesity is an important risk factor for type 2 diabetes, and ∼90% of patients with type 2 diabetes are overweight or obese (1). Among new therapies for type 2 diabetes, peptidyl mimetics of the gut-derived incretin hormone glucagon-like peptide 1 (GLP-1) stimulate insulin biosynthesis and secretion in a glucose-dependent manner (2,3) and cause modest weight loss in type 2 diabetic patients. The glucose-lowering and antiobesity effects of incretin-based therapies for type 2 diabetes have prompted evaluation of the therapeutic potential of other glucagon-family peptides, in particular oxyntomodulin (OXM). The OXM peptide is generated by post-translational processing of preproglucagon in the gut and is secreted postprandially from l-cells of the jejuno-ileum together with other preproglucagon-derived peptides including GLP-1 (4,5). In rodents, OXM reduces food intake and body weight, increases energy expenditure, and improves glucose metabolism (6–8). A 4-week clinical study in obese subjects demonstrated that repeated subcutaneous administration of OXM was well tolerated and caused significant weight loss with a concomitant reduction in food intake (9). An increase in activity-related energy expenditure was also noted in a separate study involving short-term treatment with the peptide (10).OXM activates both, the GLP-1 receptor (GLP1R) and glucagon receptor (GCGR) in vitro, albeit with 10- to 100-fold reduced potency compared with the cognate ligands GLP-1 and glucagon, respectively (11–13). It has been proposed that OXM modulates glucose and energy homeostasis solely by GLP1R agonism, because its acute metabolic effects in rodents are abolished by coadministration of the GLP1R antagonist exendin(9–39) and are not observed in Glp1r^−/− mice (7,8,14,15). Other aspects of OXM pharmacology, however, such as protective effects on murine islets and inhibition of gastric acid secretion appear to be independent of GLP1R signaling (14). In addition, pharmacological activation of GCGR by glucagon, a master regulator of fasting metabolism (16), decreases food intake in rodents and humans (17–19), suggesting a potential role for GCGR signaling in the pharmacology of OXM. Because both OXM and GLP-1 are labile in vivo (T_1/2 ∼12 min and 2–3 min, respectively) (20,21) and are substrates for the cell surface protease dipeptidyl peptidase 4 (DPP-4) (22), we developed two long-acting DPP-4–resistant OXM analogs as pharmacological agents to better investigate the differential pharmacology and therapeutic potential of dual GLP1R/GCGR agonism versus GLP1R-selective agonism. Peptide DualAG exhibits in vitro GLP1R and GCGR agonist potency comparable to that of native OXM and is conjugated to cholesterol via a Cys sidechain at the C-terminus for improved pharmacokinetics. Peptide GLPAG differs from DualAG by only one residue (Gln³→Glu) and is an equipotent GLP1R agonist, but has no significant GCGR agonist or antagonist activity in vitro. The objective of this study was to leverage the matched GLP1R agonist potencies and pharmacokinetics of peptides DualAG and GLPAG in comparing the metabolic effects and therapeutic potential of a dual GLP1R/GCGR agonist with a GLP1R-selective agonist in a mouse model of obesity.     

壤塘县藏区成人大骨节病多个大关节受累与分度的关系研究

目的研究阿坝州壤塘县藏区大骨节病（Kashin-Beck disease,KBD）多个大关节受累与分度之间的相关关系,探索成人大骨节病的合理分级标准,指导临床治疗的可行性。方法由骨科、风湿免疫科和地方病专家联合研究组设计专用调查表,采用现场流行病学调查法,包括一般情况、关节疼痛、视觉模拟疼痛评分（visual analoguescale,VAS）、关节畸形和功能障碍等,随机调查阿坝州壤塘县6个村24～93岁藏族成人大骨节病患者81例,按我国关于成人大骨节病分度标准：Ⅰ度30例,Ⅱ度30例,Ⅲ度21例。大关节定义为肩、肘、腕、髋、膝、踝共12个关节,其中任何一个关节出现疼痛、畸形或功能障碍即为大关节受累。分别统计Ⅰ、Ⅱ、Ⅲ度大骨节病患者大关节受累关节数和VAS评分。结果全部患者均存在2个以上大关节受累,其中肘关节和膝关节受累最多见,9～12个大关节受累在成人大骨节病Ⅱ度患者中比例最高,肘关节和膝关节疼痛VAS评分在成人大骨节病Ⅱ度患者中最高,踝关节受累和疼痛在Ⅲ度成人大骨节病患者中最重,肩、腕、髋关节受累及VAS评分在Ⅰ、Ⅱ、Ⅲ度成人大骨节病患者间无统计学差异,4个以上大关节受累人数在Ⅰ、Ⅱ、Ⅲ度成人大骨节病患者间无统计学差异。结论壤塘县藏区成人大骨节病患者常存在多个大关节受累,大关节受累的比例和程度与目前大骨节病分度之间无统一性;有必要对目前成人大骨节病分度进行合理的修订或改进、完善,使之更符合临床诊治并合理指导成人大骨节病的临床治疗。