血液系统恶性肿瘤患者化疗后合并中性粒细胞减少性肠炎的诊治研究

目的分析成人血液系统恶性肿瘤患者接受强烈化疗后中性粒细胞减少性肠炎（NE）的发生率、危险因素及预后情况。方法收集2004至2013年接受化疗的1804例血液系统恶性肿瘤患者，记录患者血常规、凝血检测和血液生化检测结果，并记录患者年龄、性别、原发病、既往化疗次数、既往化疗方案中是否使用阿糖胞苷、临床症状、肠壁厚度、中性粒细胞最低计数、中性粒细胞缺乏持续时间、NE的治疗方法和预后等，探讨NE起病诱因、临床特征、腹部B超特点、症状的预后意义及化疗药物对发病的影响等。结果1804例患者中226例（12.5%）化疗后合并NE，化疗后10~19d起病，中位起病时间为化疗后第14天。发生NE后26例患者死亡，病死率11.5%。化疗药物包括阿糖胞苷、临床症状≥4项、中性粒细胞缺乏持续超过7d以及B超下肠壁厚度≥10mm的患者病死率相对较高。结论NE是接受强烈化疗的血液系统肿瘤患者的严重的并发症，发生NE后患者病死率较高。     

Binding mode of conformations and structure-based pharmacophore development for farnesyltransferase inhibitors

Farnesyltransferase (FTase) is one of the prenyltransferase family enzymes that catalyse the transfer of 15-membered isoprenoid (farnesyl) moiety to the cysteine of CAAX motif-containing proteins including Rho and Ras family of G proteins. Inhibitors of FTase act as drugs for cancer, malaria, progeria and other diseases. In the present investigation, we have developed two structure-based pharmacophore models from protein–ligand complex (3E33 and 3E37) obtained from the protein data bank. Molecular dynamics (MD) simulations were performed on the complexes, and different conformers of the same complex were generated. These conformers were undergone protein–ligand interaction fingerprint (PLIF) analysis, and the fingerprint bits have been used for structure-based pharmacophore model development. The PLIF results showed that Lys164, Tyr166, TrpB106 and TyrB361 are the major interacting residues in both the complexes. The RMSD and RMSF analyses on the MD-simulated systems showed that the absence of FPP in the complex 3E37 has significant effect in the conformational changes of the ligands. During this conformational change, some interactions between the protein and the ligands are lost, but regained after some simulations (after 2 ns). The structure-based pharmacophore models showed that the hydrophobic and acceptor contours are predominantly present in the models. The pharmacophore models were validated using reference compounds, which significantly identified as HITs with smaller RMSD values. The developed structure-based pharmacophore models are significant, and the methodology used in this study is novel from the existing methods (the original X-ray crystallographic coordination of the ligands is used for the model building). In our study, along with the original coordination of the ligand, different conformers of the same complex (protein–ligand) are used. It concluded that the developed methodology is significant for the virtual screening of novel molecules on different targets.     

Intervention for arch obstruction after the Norwood procedure: Prevalence,associated factors,and practice variability

Objective

Arch obstruction after the Norwood procedure is common and contributes to mortality. We determined the prevalence, associated factors, and practice variability of arch reintervention and assessed whether arch reintervention is associated with mortality.