Mining pathway signatures from microarray data and relevant biological knowledge

High-throughput technologies such as DNA microarray are in the process of revolutionising the way modern biological research is being done. Bioinformatics tools are becoming increasingly important to assist biomedical scientists in their quest in understanding complex biological processes. Gene expression analysis has attracted a large amount of attention over the last few years mostly in the form of algorithms, exploring cluster and regulatory relationships among genes of interest, and programs that try to display the multidimensional microarray data in appropriate formats so that they make biological sense. To reduce the dimensionality of microarray data and make the corresponding analysis more biologically relevant, in this paper we propose a biologically-led approach to biochemical pathway analysis using microarray data and relevant biological knowledge. The method selects a subset of genes for each pathway that describes the behaviour of the pathway at a given experimental condition, and transforms them into pathway signatures. The metabolic pathways of Escherichia coli are used as a case study.     

Correlates of family, school, and peer variables with adolescent substance use in Taiwan

This study examines adolescent substance use in relation to family, peer and school factors in the context of Taiwan. Information on family characteristics, satisfaction with performance at school, and peer influence was collected using a case-control study in which a two-stage method was applied to ascertain substance use. A set of hypotheses on interrelationships of substance use (tobacco, alcohol, betel, illicit drugs) and influences were tested with a structural equation model. There was a strong negative relation between family factors and peer relationships (p=0.005). Family variables played an important role in motivation and effort to study (p=0.004). High motivation and effort to study (p=0.0012) and good school adjustment (p=0.078) led to higher satisfaction with performance at school. A significant positive association between peer relationships and deviant peer behaviour was observed (p<0.001). Satisfaction with performance at school was negatively related to deviant peer behaviour (p=0.052). The direct effect of deviant peer behaviour was marginally statistically significant (p=0.011) and an indirect effect of family factors on substance use was statistically significant (p=0.041). In conclusion, the study found that a strong family-peer relationship and family influence has a significant effect on substance use.     

临床路径在中国医学应用中的研究进展

目的 了解临床路径在中国临床医学中的应用状况,并从护理研究生的角度,探讨普及临床路径的方法与策略.方法 以临床路径为关键词,检索中国期刊全文数据库、中国生物医学文献数据库、万方、维普等4个常用中文数据库,对2000-2006年所得的相关文献进行统计分析.结果 4个数据库的每年文献报道数目有显著性差异(P＜0.01),逐年增加;涉及的内容分布在单病种中的治疗和护理、成本核算、用药、医院管理等方面,统计分析有显著性差异(P＜0.01),其中以临床单病种治疗和护理应用总结性的文章所占比例最高.结论 临床路径在中国医学中具有良好的发展趋势和应用前景,但仍处于萌芽阶段,需进一步探讨.护理人员在临床路径的实施中起着重要的作用,高级护理人才有助于全面推动临床路径的开展.     

Protein biomarker druggability profiling

Developing automated and interactive methods for building a model by incorporating mechanistic and potentially causal annotations of ranked biomarkers of a disease or clinical condition followed by a mapping into a contextual framework in disease-linked biochemical pathways can be used for potential drug-target evaluation and for proposing new drug targets. We demonstrate the potential of this approach using ranked protein biomarkers obtained in neonatal sepsis by enrolling 127 infants (39 infants with late onset neonatal sepsis and 88 control infants) and by performing a focused proteomic profile of the sera and by applying the interactive druggability profiling algorithm (DPA) developed by us.     

Special AT-rich sequence binding protein 1 expression correlates with response to preoperative radiotherapy and clinical outcome in rectal cancer

Our recent study showed the important role of special AT-rich sequence binding protein 1 (SATB1) in the progression of human rectal cancer. However, the value of SATB1 in response to radiotherapy (RT) for rectal cancer hasn''t been reported so far. Here, SATB1 was determined using immunohistochemistry in normal mucosa, biopsy, primary cancer, and lymph node metastasis from 132 rectal cancer patients: 66 with and 66 without preoperative RT before surgery. The effect of SATB1 knockdown on radiosensitivity was assessed by proliferation-based assay and clonogenic assay. The results showed that SATB1 increased from normal mucosa to primary cancer, whereas it decreased from primary cancer to metastasis in non-RT patients. SATB1 decreased in primary cancers after RT. In RT patients, positive SATB1 was independently associated with decreased response to preoperative RT, early time to metastasis, and worse survival. SATB1 negatively correlated with ataxia telangiectasia mutated (ATM) and pRb2/p130, and positively with Ki-67 and Survivin in RT patients, and their potential interaction through different canonical pathways was identified in network ideogram. Taken together, our findings disclose for the first time that radiation decreases SATB1 expression and sensitizes cancer cells to confer clinical benefit of patients, suggesting that SATB1 is predictive of response to preoperative RT and clinical outcome in rectal cancer.     

针灸防治心肌缺血再灌注损伤的线粒体通路研究进展

目的：探讨针灸防治心肌缺血再灌注损伤的线粒体细胞信号转导机制,为后续研究提供思路。方法:通过对近年来国内外有关线粒体心脏损伤的研究入手,分析针灸防治心肌缺血再灌注损伤的线粒体通路的研究进展。结果：研究多以大鼠为观察对象,主要从针刺改善线粒体功能,减少线粒体活性氧类（ROS）产生过量引起氧化应激,防止细胞内Ca2+超载和阻止线粒体通透性转换孔（mPTP）的开放等角度切入研究。结论：微小RNA(microRNA,miRNA)是基因网络、蛋白网络、代谢网络等的上游网络的调控环节。鉴于针灸作用的整体性特点,将miRNA引入针灸作用机制研究领域,可在基因或其他水平层面更好地揭示针灸作用机制。     

消化内科6种疾病临床路径变异原因分析及措施

目的对消化内科6种疾病变异原因进行分析总结,以便推广使用。方法对2010年3月～2011年1月119例临床路径患者变异原因进行总结、归类,通过分析讨论,制定变异控制措施。结果 119例患者中有71例患者出现不同程度的变异,变异率59.7%。有32例出现2次以上变异,其中有17例因变异而终止路径。路径终止变异率14.3%。结论在实施临床路径时,出现变异是不可避免的,有些变异会导致路径终止,而大多数变异不影响路径的完成。疾病本身因素导致变异是难以控制的;而医生及患者等主观因素导致变异是可以控制的。可控变异的主要原因是不合理用药和过度检查,须在以后加强管理。     

临床路径管理对改进医疗质量的作用分析

目的分析临床路径管理对医疗质量的影响。方法将595例实施临床路径管理的7个病种病例作为路径组,将2009年入院采用传统方法治疗的7个病种1284例作为对照组,对两组进行比较。结果7个病种实施临床路径管理后,组平均住院日、平均术前住院日缩短,外科围手术期抗生素使用天数和内科抗生素费用比显著降低,其中6个病种的药占比降低,平均住院费用有下降趋势,患者满意度提高。结论临床路径管理能缩短平均住院日,提高床位周转率,规范抗生素使用,控制医疗费用的增长,提高医疗质量水平。     

动脉粥样硬化“痰瘀”演变的内在机制研究

目的：探讨动脉粥样硬化模型大鼠随着造模时间的推移“痰瘀”演变规律.方法：采用维生素D3复合高脂饲养复制大鼠模型,动态检测血脂、血液流变学、主动脉形态学、脂质代谢相关通路基因表达的变化.结果：随着动脉粥样硬化大鼠由痰到瘀的变化即血脂、血液流变学、主动脉形态学等指标均随病情加重而变化,脂质代谢相关通路基因表达也在逐渐改变.结论：脂质代谢相关通路基因的异常表达是动脉粥样硬化大鼠由痰到瘀的分子机制.     

Assessing the Quality of Care for Dying Patients From the Bereaved Relatives' Perspective: Further Validation of “Evaluating Care and Health Outcomes–for the Dying”

ContextEvaluating Care and Health Outcomes–for the Dying (ECHO-D) is a post-bereavement questionnaire that assesses quality of care for the dying and is linked with the Liverpool Care Pathway for the Dying Patient (LCP).ObjectivesTo further assess the validity and reliability of the ECHO-D, namely the construct validity, internal consistency, and test-retest reliability of key composite scales.MethodsSelf-completion questionnaires were mailed to 778 next-of-kin of consecutive deceased patients who had died an “expected” cancer death in a hospice or acute tertiary hospital. For those willing to complete ECHO-D for a second time, another copy was sent a month later. Maximum likelihood factor analysis and Cronbach's alpha test were conducted for four key composite scales. Test-retest reliability was assessed using percentage agreement, Kappa statistic, and Spearman's correlation coefficient (ordinal data). Comparisons between hospice and hospital groups were conducted using one-way between-groups analysis of variance.ResultsFollowing exclusions (n = 52), 255 of 726 next-of-kin agreed to participate (35.2% response rate). Maximum likelihood factor analysis showed a single factor for three of the scales, and all had good internal consistency (Cronbach's alpha >0.78). Barring two questions, all showed good or moderate stability over time. Overall, hospice participants reported the best quality of care, and hospital participants, where care was not supported by the LCP, reported the worst quality of care.ConclusionThese findings support ECHO-D as a valid and reliable instrument to assess quality of care for the dying and assess the effectiveness of interventions such as the LCP.