临床路径在腹腔镜胆囊切除术中的应用

目的探讨临床路径在腹腔镜胆囊切除术中的应用效果。方法选择240例行腹腔镜胆囊切除术患者,按入院先后顺序随机分为观察组和对照组,每组120例。观察组采用临床路径进行管理,对照组给予传统的护理模式进行管理,比较两组的各项临床指标。结果观察组与对照组的住院时间分别为（4．3±1．5）天和（6．5±1．8）天;住院费用分别为（5995．7±448．9）元和（6523．8±665．2）元;肛门排气时间分别为（29．4±7．9）小时和（43．2±18．8）小时;患者满意度分别为（98．8±2．2）％和（95．0±6．3）％,组间比较差异有统计学意义（P〈0．05）。结论临床路径作为一种科学的诊疗及护理模式,应用于腹腔镜胆囊切除术,可以缩短住院时间,促进术后患者胃肠道恢复,降低住院费用,提高患者的满意度,值得在临床中推广应用。     

The machinery of Nod-like receptors: refining the paths to immunity and cell death

One of the fundamental aspects of the innate immune system is its capacity to discriminate between self and non-self or altered self, and to quickly respond by eliciting effector mechanisms that act in concert to restore normalcy. This capacity is determined by a set of evolutionarily conserved pattern recognition receptors (PRRs) that sense the presence of microbial motifs or endogenous danger signals, including tissue damage, cellular transformation or metabolic perturbation, and orchestrate the nature, duration and intensity of the innate immune response. Nod-like receptors (NLRs), a group of intracellular PRRs, are particularly essential as evident by the high incidence of genetic variations in their genes in various diseases of homeostasis. Here, I overview the signaling mechanisms of NLRs and discuss the mounting evidence of evolutionary conservation between their pathways and the cell death machinery. I also describe their effector functions that link the sensing of danger to the induction of inflammation, autophagy or cell death.     

The TGF-β signaling modulators TRAP1/TGFBRAP1 and VPS39/Vam6/TLP are essential for early embryonic development

The pleiotropic cytokine transforming growth factor-β (TGF-β) signals through different pathways among which the Smad- and the MAP-Kinase pathways are already well characterized. Both pathways utilize adaptor/chaperone molecules that facilitate or modulate the intracellular signaling events. Two of the proteins shown in vitro to play a role in Smad-dependent signaling are the TGF-β Receptor Associated Protein-1 (TRAP1, also TGFBRAP1) and its homologue VPS39, also known as Vam6 and TRAP1-Like-Protein (TLP). We generated mice deficient for TRAP1 and VPS39/TLP, respectively. Absence of TRAP1 protein results in death at either of two defined timepoints during embryogenesis, before the blastula stage or during gastrulation, whereas most of the VPS39 deficient mice die before E6.5. Heterozygous mice show no overt phenotype. In summary, our data indicate that TRAP1 and VPS39 are nonredundant and essentially required for early embryonic development.     

Extracellular proteinase formation in carbon starving Aspergillus nidulans cultures--physiological function and regulation

Extracellular proteinase formation in carbon depleted cultures of the model filamentous fungus Aspergillus nidulans was studied to elucidate its regulation and possible physiological function. As demonstrated by gene deletion, culture optimization, microbial physiological and enzymological experiments, the PrtA and PepJ proteinases of A. nidulans did not appear to play a decisive role in the autolytic decomposition of fungal cells under the conditions we tested. However, carbon starvation induced formation of the proteinases observable in autolytic cultures. Similar to other degradative enzymes, production of proteinase was regulated by FluG-BrlA asexual developmental signaling and modulated by PacC-dependent pH-responsive signaling. Under the same carbon starved culture conditions, alterations of CreA, MeaB or heterotrimeric G protein mediated signaling pathways caused less significant changes in the formation of extracellular proteinases. Taken together, these results indicate that while the accumulation of PrtA and PepJ is tightly coupled to the initiation of autolysis, they are not essential for autolytic cell wall degradation in A. nidulans. Thus, as Aspergillus genomes contain a large group of genes encoding proteinases with versatile physiological functions, selective control of proteinase production in fungal cells is needed for the improved industrial use of fungi.     

细胞因子信号转导抑制因子1和3在脓毒症小鼠脾脏中表达量的变化

目的探讨细胞因子信号转导抑制因子-1和3（SOCS1和SOCS3）的含量在脓毒症小鼠脾脏中的变化情况以及可能的作用机制。方法采用盲肠结扎并穿刺术（CLP）制作脓毒症模型,提取脾脏组织的RNA及蛋白质,采用RT-PCR测定组织中SOCS1和SOCS3 mRNA的相对含量,用免疫印迹方法测定组织中SOCS1和SOCS3相对蛋白含量,用SPSS统计软件测定上述指标之间的变化关系。结果脓毒症手术后SOCS1在脾脏中仅检测到基因表达,随时间逐渐上升,并一直保持高位;SOCS3在脾脏内的基因表达和蛋白表达在术后2h迅速升高,至12h达峰值（P〈0.05）;统计分析发现SOCS1和SOCS3的基因表达呈明显正相关性（P〈0.05）。结论 CLP导致的脓毒症可以诱导SOCS1和SOCS3在脾脏中表达增多,提示SOCS1和SOCS3在脓毒症出现后的免疫变化中有重要作用,可能可利用它们对脓毒症进行干预,以改善脓毒症的预后。     

DAPT抑制RM-1细胞增殖的实验研究

目的研究Notch信号通路特异性阻断剂DAPT对小鼠前列腺癌RM-1细胞增殖的影响。方法体外培养RM-1细胞,实验组以不同浓度DAPT（0.25、0.5、1、2、5μmol/L）处理,对照组不加DAPT;利用MTT法检测细胞增殖,流式细胞术检测细胞周期（PI法）,RT-PCR法检测Notch1、Jagged1基因表达。结果与对照组比较,0.25μmol/L剂量组对RM-1细胞增殖、周期、Notch1及Jagged1 mRNA表达的影响无差异;0.5、1、2、5μmol/L剂量组均能显著抑制RM-1细胞增殖,随着DAPT浓度的增加,G0/G1期细胞比例逐渐增多,S期细胞比例逐渐减少,G2/M期细胞比例无明显差异,Notch1、Jagged1 mRNA的表达逐渐下调。结论当DAPT浓度≥0.5μmol/L时能够抑制RM-1细胞的增殖,且呈剂量依赖性,其机制可能与诱导细胞G0/G1期阻滞、Notch1及Jagged1 mRNA的表达下调有关。     

基于临床路径的乳腺癌患者术后生存质量影响因素分析

目的 探讨临床路径对乳腺癌患者术后生存质量的影响及在该病种的应用效果.方法 应用世界卫生组织生存质量量表简表(WHQOL-BRIEF),对比纳入乳腺癌临床治疗路径方案的患者前后生存质量变化情况并对术后生存质量的影响因素进行分析.结果 通过我院"乳腺癌临床路径诊疗方案"治疗可提高患者生存质量,并且术后生存质量的影响因素分别为手术方式、病程长短、年龄、生长方式、病理分化程度.结论 实施临床路径后可显著提高乳腺癌患者的术后生存质量,同时,从不同患者的手术方式、病程长短、年龄、生长方式、病理分化程度这五个方面入手,在临床工作中不断总结经验并针对性的采取医疗护理措施可以进一步的提高患者的术后生存质量.     

Synthesis of potent dishevelled PDZ domain inhibitors guided by virtual screening and NMR studies

Dishevelled (Dvl) PDZ domains transduce Wnt signals from the membrane-bound receptor Frizzled to the downstream. As abnormal Wnt signaling has been implicated in tumorigenesis, the Dvl PDZ domain is a potential target for small-molecule inhibitors that block Wnt signaling at the Dvl level. We expanded our in silico search to examine the chemical space near previously developed PDZ binders and identified nine additional compounds bind to the Dvl PDZ. We then performed a quantitative structure-activity relationship (QSAR) analysis of these compounds and combined these results with structural studies of the PDZ domain in complex with the compounds to design and synthesize a group of new, further optimized compounds. Two rounds of synthesis and testing yielded a total of six compounds that have greatly improved binding affinity to the Dvl PDZ domain and most potent ones competitively displace Dapper peptide from the PDZ domain. In addition to providing more potent Dvl PDZ domain inhibitors, this study demonstrates that virtual screening and structural studies can be powerful tools in guiding the chemical synthesis hit-to-lead optimization stage during the drug discovery process.