An orally administrated nucleotide-delivery vehicle targeting colonic macrophages for the treatment of inflammatory bowel disease

Tumor necrosis factor-alpha (TNF-α) plays a central role in the pathogenesis of inflammatory bowel disease (IBD). Anti-TNF-α therapies have shown protective effects against colitis, but an efficient tool for target suppression of its secretion - ideally via oral administration - remains in urgent demand. In the colon tissue, TNF-α is mainly secreted by the colonic macrophages. Here, we report an orally-administrated microspheric vehicle that can target the colonic macrophages and suppress the local expression of TNF-α for IBD treatment. This vehicle is formed by cationic konjac glucomannan (cKGM), phytagel and an antisense oligonucleotide against TNF-α. It was given to dextran sodium sulfate (DSS) colitic mice via gastric perfusion. The unique swelling properties of cKGM enabled the spontaneous release of cKGM& antisense nucleotide (ASO) nano-complex from the phytagel scaffold into the colon lumen, where the ASO was transferred into colonic macrophages via receptor-mediated phagocytosis. The treatment significantly decreased the local level of TNF-α and alleviated the symptoms of colitis in the mice. In summary, our study demonstrates a convenient, orally-administrated drug delivery system that effectively targets colonic macrophages for suppression of TNF-α expression. It may represent a promising therapeutic approach in the treatment of IBD.     

松质骨基质复合生物蛋白胶构建组织工程软骨的研究

目的尝试采用松质骨基质与生物蛋白胶复合材料构建组织工程软骨。方法体外培养大鼠软骨细胞,接种于松质骨基质／生物蛋白胶材料上行体外培养。采用HE、甲苯胺蓝染色免疫学检测、扫描电镜观察等方法观察所构建的组织工程软骨的特性。结果松质骨基质／生物蛋白胶组的组织学结构更接近于软骨样组织．其Ⅱ型胶原、蛋白多糖基因表达量及蛋白多糖含量明显高于松质骨基质组。结论松质骨基质／生物蛋白胶复合材料可用于构建组织工程软骨,是一种较理想的支架材料。     

表浅膀胱肿瘤电切术后膀胱内药物灌注预防肿瘤复发的临床观察

目的 观察表浅膀胱肿瘤电切术后膀胱内灌注丝裂霉素和吡柔比星预防肿瘤复发的疗效和安全性.方法 回顾性分析我科2007年2月至2009年10月间收治的130例表浅膀胱肿瘤患者的临床资料,所有患者均行经尿道膀胱肿瘤电切和术后膀胱内灌注丝裂霉素或吡柔比星,其中术后膀胱内灌注丝裂霉素70例,吡柔比星60例.观察术后1年肿瘤复发和灌注药物的副作用.结果 ①术后膀胱内灌注丝裂霉素和吡柔比星的1年复发率分别为11.4%（8/70）和16.7%（10/60）（P＞0.05）.在丝裂霉素组,病理分级G1、G2、G3级肿瘤1年复发率分别为12.2%、8%和25%,它们之间无显著差异（P＞0.05）;在吡柔比星组,病理分级G1、G2、G3级肿瘤1年复发率分别为4%、12.5%和54.5%,其中G3级肿瘤复发率明显高于G1和G2级肿瘤（P＜0.05）.②130例患者中,进行即刻膀胱内药物灌注（24h内）和非即刻灌注的1年复发率分别为4%（1/25）和16.2%（17/105）,两者之间有显著性差异（P＜0.05）.③灌注丝裂霉素和吡柔比星后全身副作用发生率分别为18.5% 和 1.5%（P＜0.05）,局部副作用发生率分别为4.3% 和 33.3%（P＜0.05）.结论 术后膀胱内灌注丝裂霉素和吡柔比星预防肿瘤复发的效果无显著性差异,但G3级肿瘤的复发率高于G1和G2级肿瘤,对其灌注方案有待进一步研究;术后即刻膀胱内药物灌注可有效降低肿瘤1年复发率,值得推广;术后膀胱内灌注丝裂霉素和吡柔比星的副作用在全身和局部发生率不同,但均可耐受;由于观察时间短和例数有限,观察结果有待进一步研究.     

SPO11基因单核苷酸多态性与陕西回族人群非梗阻性无精症相关性研究

目的探讨SPO11基因单核苷酸多态性在陕西回族非梗阻性无精症人群中的分布及其与无精症发病风险的关联。方法采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法,分析40例陕西回族非梗阻性无精症患者和45例陕西回族正常对照男性SPO11基因SNP位点（rs28368082）的基因分型和等位基因频率,以及其与非梗阻性无精症发病的相关性。结果 SPO11基因SNP位点（rs28368082）的CC,CT两种基因型频率在病例和对照组中分布存在显著性差异（P=0.048）,携带CT基因型的个体患非梗阻性无精症的风险是CC基因型的7.76倍（95%CI=0.89～66.58）。结论SPO11基因SNP位点（rs28368082）与陕西回族人群非梗阻性无精症发病风险存在关联,可能是陕西回族人群非梗阻性无精症的遗传易感基因之一。     

慢性病自我管理的研究实践及问题探讨

慢性病自我管理是近年来国际上兴起的针对慢性病患者有效控制和管理的方法,在我国也日益受到关注和重视,但还未达到普遍认同和广泛推广的程度。该文通过分析近年来我国慢性病的流行现状,在简要介绍自我管理相关概念和内容的基础上,借鉴目前国内外对慢性病自我管理所做的研究与实践,探讨慢性病自我管理模式在实施中存在的问题,并提出相应对策,为在我国进一步推广和实施慢性病自我管理提供参考和依据。     

建立小鼠增生性瘢痕动物模型的研究

目的:应用小鼠建立自身产生的、与人类类似的增生性瘢痕动物模型。方法:在小鼠耳耳腹面形成边长约3mm的方形全层皮肤缺损创面,愈合后,用计数细胞层数的方法对增生块进行病理学观察,比较瘢痕增生程度。结果:小鼠耳腹面可产生类似于人类的增生性瘢痕。外观明显产生增生80%。结论:这一动物模型可能成为研究人类瘢痕的动物模型。     

Topographical distributions of endomorphinergic pathways from nucleus tractus solitarii to periaqueductal gray in the rat

In the central nervous system (CNS), endomorphin 1 (EM1)- and endomorphin 2 (EM2)-containing neuronal cell bodies have been found in the nucleus tractus sollitarii (NTS) and the hypothalamus, and EMergic fibers and terminals are distributed widely in many regions of the CNS, including the periaqueductal gray (PAG). The aim of the present study was to examine whether EM-expressing neurons in the NTS of the rat send their axons to the PAG, and determine whether the EMergic pathway from the NTS to the PAG is topographic by using. Immunofluorescent staining for EM1 or EM2 combined with retrograde and anterograde tract-tracing methods. The results showed that after injecting tetramethyl rhodamine dextran-amine (TMR) into the ventrolateral or lateral column of the PAG, some EM1- or EM2-immunoreactive (IR) neurons in the NTS were retrogradely labeled with TMR, and the majority of the EM-IR/TMR double-labeled neurons were mainly distributed in the medial and commissural subnuclei of the NTS. Following injection of biotinylated dextran amine (BDA) into the medial or commissural subnucleus of the NTS, EM1-IR/BDA and EM2-IR/BDA double-labeled fibers and terminals were mainly distributed in the ventrolateral or lateral column of the PAG, respectively. The results indicate that EMergic pathway from the NTS to PAG is topographically organized, and suggest that EMs released from NTS to PAG projecting terminals may bind to μ-opioid receptor on the PAG neurons, and thereby contribute to various functions.     

Antenatal Rh prophylaxis is unnecessary for “Asia type” DEL women

BackgroundGenerally Rh-negative patients need to be transfused with Rh-negative red blood cells. For pregnant women carrying Rh-positive fetus, the antenatal anti-D detection and Rh immunoglobulin prophylaxis are required worldwide. In East Asia, a RhD variant, termed “Asia type” DEL, was found in approximately 30% of apparent Rh-negative individuals. The antigenic and molecular properties of the DEL were previously defined. Few data discuss whether DEL could be immunized by D antigen clinically although DEL was reported arousing alloimmunization to true Rh-negative patients.Study design and methodsTo determine whether the DEL variant can be immunized to the D antigen, we retrospectively evaluated 104 Rh-negative pregnancies with allo-anti-D antibodies, and we also tracked 199 consecutive apparent Rh-negative pregnant women, with a history of gestations or parturitions but not subject to anti-D gamma-globulin prophylaxis, for evidence of allo-anti-D. The DEL variant was first excluded by ccee phenotypes and then identified through PCR analysis or sequencing.ResultsIn the retrospective study, we expected to find 30 DEL variants, yet none of the anti-D alloimmunized women were DEL-positive. And in the second group, none of 44 DEL-positive women versus 38 of 155 (24.5%) true Rh-negative women (those excluding DEL) formed allo-anti-D.ConclusionThe data indicate that the “Asia type” DEL variant does not appear at risk of alloimmunization to the D antigen. It strongly suggests that the antenatal Rh immune globulin prophylaxis is unnecessary for DEL women. Furthermore, it implicates that the “Asia type” DEL may be deemed Rh-positive safely for clinical transfusion therapy.