Systematic review of therapies for noncyclic chronic pelvic pain in women

Drug screening is often limited to cell-free assays involving purified enzymes, but it is arguably best applied against systems that represent disease states or complex physiological cellular networks. Here, we describe a high-content, cell-based drug discovery platform based on phosphospecific flow cytometry, or phosphoflow, that enabled screening for inhibitors against multiple endogenous kinase signaling pathways in heterogeneous primary cell populations at the single-cell level. From a library of small-molecule natural products, we identified pathway-selective inhibitors of Jak-Stat and MAP kinase signaling. Dose-response experiments in primary cells confirmed pathway selectivity, but importantly also revealed differential inhibition of cell types and new druggability trends across multiple compounds. Lead compound selectivity was confirmed in vivo in mice. Phosphoflow therefore provides a unique platform that can be applied throughout the drug discovery process, from early compound screening to in vivo testing and clinical monitoring of drug efficacy.     

分类树模型在重症手足口病风险预测中的应用

目的:应用分类树模型构建重症手足口病的预测模型,并评价其应用价值。方法:整群抽取河南省郑州市某医院2013年4月至6月住院治疗的221例发病时间≤72 h的手足口病患儿为研究对象,采用CHAID分类树算法建立重症手足口病的预测模型,采用错分概率Risk值、索引图及受试者工作特征曲线评价模型的应用价值。结果:所建立的分类树模型包括3层,共9个结点,共筛选出4个解释变量:精神差、易惊、热峰≥39℃、手足抖动;其中最为重要的预测因素为精神差和易惊。模型错分概率Risk值为0.045,模型拟合的效果较好。结论:分类树模型不仅能有效地拟合重症手足口病的风险预测,还可以对变量间的交互作用进行有效的筛选。     

Antenatal platelet antibody testing by flow cytometry—results of a pilot study

BACKGROUND: Maternal platelet antibodies can cause fetomaternal alloimmune thrombocytopenia (FMAT), which has significant mortality and morbidity even in a first pregnancy. Prenatal diagnosis of FMAT has not previously been possible in the first affected pregnancy. STUDY DESIGN AND METHODS: Using flow cytometry, a sensitive, inexpensive test for the detection of platelet antibodies has been developed. It was adapted for use as a possible antenatal screening test, and 600 pregnant women were tested in a pilot study. RESULTS: In the study group, two women tested positive for platelet-specific IgG antibodies, one for anti-HPA- 1a and the other for anti-HPA-1a with anti-HLA. In each case, the fetus was found to be affected in utero, and treatment was initiated before successful delivery. Another woman was shown to have a platelet- reactive autoantibody without IgG specificity, and her infant was unaffected. A total of 95 (15.8%) of the women tested had HLA antibodies alone, and the majority demonstrated IgG specificity. On follow-up of 62 infants born to these women, none had thrombocytopenia; thus HLA antibodies were not shown to lead to FMAT in this study. CONCLUSION: The flow cytometry-based test for platelet antibodies can detect clinically significant maternal antibodies, and it may be that early diagnosis and treatment in utero can enhance outcome in FMAT. A population screening program is planned to determine the predictive power of this test, in addition to its sensitivity, specificity, and efficiency.