Evodiamine-inspired dual inhibitors of histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) with potent antitumor activity

A great challenge in multi-targeting drug discovery is to identify drug-like lead compounds with therapeutic advantages over single target inhibitors and drug combinations. Inspired by our previous efforts in designing antitumor evodiamine derivatives, herein selective histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) dual inhibitors were successfully identified, which showed potent in vitro and in vivo antitumor potency. Particularly, compound 30a was orally active and possessed excellent in vivo antitumor activity in the HCT116 xenograft model (TGI = 75.2%, 150 mg/kg, p.o.) without significant toxicity, which was more potent than HDAC inhibitor vorinostat, TOP inhibitor evodiamine and their combination. Taken together, this study highlights the therapeutic advantages of evodiamine-based HDAC1/TOP2 dual inhibitors and provides valuable leads for the development of novel multi-targeting antitumor agents.     

User experiences with second-generation 32-gauge × 4 mm vs. thinner comparator pen needles: prospective randomized trial

Abstract

Objective

Two similarly designed studies compared user experiences with a second-generation extra-thin-wall, 5-bevel 32?G?×?4?mm pen needle (PN) with redesigned hub versus four thinner commercially available PNs.     

High-Pressure Water Swelling Sealant Injection Injury to the Hand: a Case Report and Review of the Literature

High-pressure injection injuries (HPII) caused by water swelling sealant are rare at present. The patient generally has small-sized skin lesions, and the misleadingly benign presentation may cause delayed treatment at the early stage of management. In addition, radiographic examination may be underestimated. Subsequently, the inadequate surgical intervention may cause tissue necrosis and poor prognosis. Furthermore, the early recognition of water swelling sealant injected into tissue and emergent surgical intervention are the key to successful management for the patient with HPII caused by injecting water swelling sealant to tissue.     

参麦注射液对冠心病患者的治疗作用

目的 观察参麦注射液治疗冠心痛的临床效果.方法 选取我院2013年4月-2014年1月间收治的冠心病患者94例,依据治疗方案不同分为治疗组48例,对照组46例,2组患者入院均根据病情给予能量合剂、血管扩张剂、减轻心脏负荷药物,并进行对症、溶栓及抗心律失常等常规治疗,治疗组患者在常规治疗的基础上给予参麦注射液静滴治疗,1次/d,用药2周为1疗程;于治疗2疗程后观察治疗效果,并对比2组患者临床症状、心电图改善情况及红细胞超氧化物歧化酶(E-SOD)平均活性,血浆过氧化脂质(P-LPO)、红细胞过氧化脂质(E-LPO)含量变化.结果 治疗组治疗后总有效率显著高于对照组(P＜0.05);治疗组胸闷、心悸、心绞痛及ST段下移、T渡低平或倒置患者改善率显著均高于对照组(P＜0.05);治疗组治疗后E-SOD活性显著高于对照组,P-LPO、E-LPO含量显著低于对照组(P＜0.05).结论 参麦注射液可有效缓解冠心病患者临床症状,降低血中脂质过氧化物浓度,缓解心肌缺血状态.     

嵌顿痔不同治疗方法疗效分析

目的探讨嵌顿痔不同治疗方法的疗效。方法回顾性分析2009年8月至2012年8月迁西县人民医院确诊为嵌顿痔的160例患者的临床资料,其中采取外剥内扎法的80例患者作为A组,吻合器痔上黏膜环切术(PPH)结合外痔血栓剥除术的80例患者作为B组。对比分析两组患者的手术时间、住院时间、住院费用等指标及临床疗效,对比分析两组术后6个月并发症发生情况。结果B组患者的手术时间、住院时间显著少于A组[(15.4±1.1)min比(38.7±0.5)min,(5.3±0.6)d比(12.4±1.3)d,P<0.01];B组患者的有效率显著高于A组(88.8%比66.3%),而总体并发症发生率及复发率显著低于A组(17.5%比33.8%,5%比18.8%,P<0.05)。结论 PPH结合外痔血栓剥除术临床疗效显著。