胆源性胰腺炎大鼠胰腺胆囊收缩素受体变化的实验研究

目的　探讨胆源性胰腺炎（biliarypancreatitis,BP）大鼠胰腺胆囊收缩素受体（cholecystokininreceptor,CCK-R）和血浆胆囊收缩素八肽（cholecystokininoctapeptide,CCK-OP）的变化及其之间的关系。　方法　采用放射受体分析法检测36只BP大鼠及36只对照组大鼠胰腺组织膜CCK-R和竞争性酶联免疫法检测其血浆CCK-OP的含量。　结果　胆胰管结扎后3h、6h及24h胰腺组织膜CCK-R的最大结合容量（Bmax）值为179.0±1.1、119.0±1.8、及114.0±1.4fmol/ml;平衡解离常数Kd值为0.26±0.01、0.13±0.07、0.14±0.01nM;6h及24hBmax值和Kd值与对照大鼠存在显著差异(P均＜0.05)。BP大鼠血浆CCK-OP含量各为12.55±2.10、0.81±0.16、0.79±0.24PM/L;与正常大鼠相比,胰腺CCK-R在术后6h及24h期间结合位点数减少,亲合力增大（P＜0.05）;血浆CCK-OP含量仅在术后3h与对照组大鼠差异有显著性意义（P＜0.05）。　结论　BP大鼠发病过程中,胰腺CCK-R及血浆CCK-OP均发生了明显的变化。     

心源性脑卒中诊断中血生化标志物检查的临床应用

目的寻找较为有效可行的血生化标志物应用于脑卒中病因学诊断,从而指导临床卒中亚型（尤其是心源性卒中）的明确诊断和后续进一步治疗与预防的开展。方法收集本院神经内科2008年1月至2008年12月间因急性脑卒中住院患者的临床资料。所有患者均经脑CT、磁共振成像（MRI）、心脑血管超声及其他检查手段确诊,并经TOAST分类标准进行病因学评估鉴定。血样于患者急诊入院后24h内采样,进行如下数种血生化标志物检查：C反应蛋白（CRP）,D-二聚体（D—dimer,DD）,脑钠肽（BNP）（均使用ELISA法测定）。并根据检查结果分析卒中亚型诊断中上述血生化标志物的临床应用价值。结果入选71例急性缺血性脑卒中患者。与其他亚型卒中患者比较,在心源性卒中患者中,检查发现存在较高水平的BNP与DD表达（P〈0．05）。结论使用上述血生化标志物检查,可能成为急性期心源性卒中诊断的一种较为可行有效的诊断方法,并指导其他进一步诊断性检查及后续防治措施的开展。     

噬菌体表面表达随机8肽文库的构建

目的:构建噬菌体表面表达随机8肽文库;方法: 采用人工合成随机寡核苷酸、基因重组技术,噬菌体表面表达技术等,构建该文库;采用多聚酶链式反应技术、核酸杂交技术和测序分析评价鉴定。多聚酶链式反应所采用的上游引物包括载体克隆位点处部分碱基和部分外源基因的碱基;在核酸杂交中设计了噬菌体载体克隆位点互补探针,以更加准确地排除无外源基因插入的克隆;在测序鉴定中,选择了2个混合探针杂交阳性的克隆。 结果:以上证实获得独特克隆为2.1×10⁸;亲和富集实验证实所建噬菌体文库可以稳定扩展。结论:我们成功地构建了噬菌体随机8肽文库,其库容量为2.1×10⁸。     

Peptide radiopharmaceuticals in nuclear medicine

This article reviews the labelling of peptides that are recognised to be of interest for nuclear medicine or are the subject of ongoing nuclear medicine research. Applications and approaches to the labelling of peptide radiopharmaceuticals are discussed, and drawbacks in their development considered.     

Mass spectrometry-based serum peptide profiling in hepatocellular carcinoma with bone metastasis

AIM:To investigate the potential of serum peptides as a diagnostic tool for hepatocellular carcinoma(HCC)with bone metastasis.METHODS:Matrix-assisted laser desorption ionization-time of flight mass spectrometry(MALDI-TOF-MS)was used to characterize the serum peptide profile of HCC patients with bone metastasis.Serum samples from 138 HCC patients(66 cases with and 72 cases without bone metastasis)were randomly assigned into a training set(n=76)and a test set(n=62).Differential serum peptides were examined using ClinProt magnetic bead-based purification followed by MALDITOF-MS.The sequences of differentially expressed serum peptides were identified using liquid chromatography-mass spectrometry.A diagnostic model was established using a learning algorithm of radial basis function neural network verified by a single blind trial.Receiver operating characteristic(ROC)analysis was performed to evaluate the diagnostic power of the established model.RESULTS:Ten peptide peaks were significantly different between HCC patients with or without bone metastasis(P<0.001).Sequences of seven peptides with mass to charge ratios(m/z)of 1780.7,1866.5,2131.6,2880.4,1532.4,2489.8,and 2234.3 were successfully identified.These seven peptides were derived from alpha-fetoprotein,prothrombin,serglycin,isoform2 of inter-alpha-trypsin inhibitor heavy chain H4,isoform 1 of autophagy-related protein 16-2,and transthyretin and fibrinogen beta chains,respectively.The recognition rate and predictive power of a diagnostic model established on the basis of six significant peptides(m/z for these six peptides were 1535.4,1780.7,1866.5,2131.6,2880.4,and 2901.9)were 89.47%and82.89%,respectively.The sensitivity and specificity of this model based upon a single blind trial were 85.29%and 85.71%,respectively.ROC analysis found that the AUC(area under the ROC curve)value was 0.911.CONCLUSION:Our study suggested that serum peptides may serve as a diagnosis tool for HCC bone metastasis.     

Oral delivery of proteins and peptides: Challenges,status quo and future perspectives

Proteins and peptides (PPs) have gradually become more attractive therapeutic molecules than small molecular drugs due to their high selectivity and efficacy, but fewer side effects. Owing to the poor stability and limited permeability through gastrointestinal (GI) tract and epithelia, the therapeutic PPs are usually administered by parenteral route. Given the big demand for oral administration in clinical use, a variety of researches focused on developing new technologies to overcome GI barriers of PPs, such as enteric coating, enzyme inhibitors, permeation enhancers, nanoparticles, as well as intestinal microdevices. Some new technologies have been developed under clinical trials and even on the market. This review summarizes the history, the physiological barriers and the overcoming approaches, current clinical and preclinical technologies, and future prospects of oral delivery of PPs.     

载脂蛋白B mRNA编辑酶催化多肽家族在病毒性疾病中的研究进展

载脂蛋白B mRNA编辑酶催化多肽家族是一种通过脱氨酶作用编辑DNA和RNA序列的抗病毒活性蛋白分子.最初载脂蛋白B mRNA编辑酶催化多肽3家族因具有抑制HIV复制的作用而得到关注.随着研究的深入,发现载脂蛋白B mRNA编辑酶催化多肽家族在与人类疾病密切相关的其他病毒感染如人类嗜T细胞病毒、丙型肝炎病毒、乙型肝炎病毒、人乳头瘤病毒、单纯疱疹病毒中同样发挥重要作用.此外,载脂蛋白B mRNA编辑酶催化多肽的编辑作用不仅是病毒基因多样性和进化性的来源,也是肿瘤发生的重要原因.     

Cachexia and neuropeptide Y

Cachexia or wasting disease occurs commonly in diseases that have an overproduction of proinflammatory cytokines associated with them. The hallmarks of cachexia are loss of lean and adipose tissue, anorexia, anemia, memory disturbance, and sickness behavior. This review suggests that increased inducible nitric oxide synthase production in the hypothalamus leads to severe anorexia and that this is the pathway through which proinflammatory cytokines produce anorexia. Orexigenic peptides, such as neuropeptide, ghrelin, and orexin A, and anorectic peptides, such as leptin, produce their effects through neuronal nitric oxide synthase. Activation of neuronal nitric oxide synthase results in increased adenosine monophosphate kinase and a decrease in malonyl coenzyme A, leading to increased food intake.     

微囊藻毒素LR对DNA和自然杀伤细胞的损伤效应研究

目的：研究和探讨微囊藻毒素LR（microcystins LR,MCLR)的致癌和促癌机制。方法：用单细胞微量凝胶电泳技术和^3H-TdR释放法研究了MCLR对大鼠DNA及小鼠自然杀伤细胞（NK细胞）的损伤效应。结果：研究表明,不同剂量的MCLR均可引起大鼠淋巴细胞DNA的损伤,其DNA迁移长度与对照组相比差异有高度显性;随着剂量的增加和注射时间的延长对DNA的损伤效应未发生现明显剂量反应关系;且在停止注射后DNA的损伤很快可得到修复。同时体内和体外动物试验还显示,MCLR可降低小鼠NK细胞对YAC－1细胞的杀伤性,与对照组相比其差别有显性,结论：本研究将为进一步从分水平及细胞水平阐明MCLR的促癌、致癌机制提供理论依据。