Recent advances in construction of small molecule-based fluorophore-drug conjugates

As a powerful tool to advance drug discovery, molecular imaging may provide new insights into the process of drug effect and therapy at cellular and molecular levels. When compared with other detection methods, fluorescence-based strategies are highly attractive and can be used to illuminate pathways of drugs’ transport, with multi-color capacity, high specificity and good sensitivity. The conjugates of fluorescent molecules and therapeutic agents create exciting avenues for real-time monitoring of drug delivery and distribution, both in vitro and in vivo. In this short review, we discuss recent developments of small molecule-based fluorophore-drug conjugates, including non-cleavable and cleavable ones, that are capable of visualizing drug delivery.     

重庆大娄山脉毛茛科珍贵药用植物及民间验方

本文介绍在第四次全国中药资源普查中对重庆大娄山脉的调查,从民间收集珍贵的中草药传统使用经验及知识。通过访问并采集相关的植物标本,整理出8种毛茛科珍贵草药——金山铜骨七、金山拐枣七、金山绿升麻、金山拐子药、金山鸡爪连、溪边飞蛾七、金山岩乌头、雪上一枝蒿,并对其基源植物、凭证标本、采集加工、单验方进行梳理。     

Incidence of T790M in Patients With NSCLC Progressed to Gefitinib,Erlotinib, and Afatinib: A Study on Circulating Cell-free DNA

BackgroundInsights into the mechanism of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) could provide important information for further patient management, including the choice of second-line treatment. The EGFR T790M mutation is the most common mechanism of resistance to first- and second-generation EGFR TKIs. Owing to its biologic relevance in the response of non–small-cell lung cancer (NSCLC) to the selective pressure of treatment, the present study investigated whether the occurrence of T790M at progression differed among patients receiving gefitinib, erlotinib, or afatinib.Patients and MethodsThe present retrospective study included patients with NSCLC with an EGFR activating mutation, who had received gefitinib, erlotinib, or afatinib as first-line treatment. Plasma samples for the analysis of cell-free DNA were taken at disease progression and analyzed using a digital droplet polymerase chain reaction EGFR mutation assay.ResultsA total of 83 patients were enrolled; 42 had received gefitinib or erlotinib and 41afatinib. The patient characteristics were comparable across the 2 groups. The median time to progression (TTP) was 14.4 months for the gefitinib and erlotinib group and 10.2 months for the afatinib group (P = .09). Of the 83 patients, 47 (56.6%) were positive for the T790M in plasma. A greater incidence of T790M was observed in patients with progression during gefitinib or erlotinib therapy compared with patients treated with afatinib (33 [79%] vs. 14 [34%], respectively; odds ratio, 7.1; 95% confidence interval, 2.7-18.5; P = .0001).ConclusionsAlthough gefitinib, erlotinib, and afatinib showed a comparable TTP in patients receiving first-line therapy, the incidence of T790M differed among them, as demonstrated by the present study, which could have implications for the choice of second-line treatment.     

神经外科重症监护病房常见病原菌的分布与耐药性研究

目的调查珠江医院神经外科重症监护病房(ICU)病原菌的分布与耐药情况,分析ICU院内感染的发生原因,探讨防治对策。方法应用法国VITEKⅡ全自动细菌鉴定仪鉴定病原菌,用纸片扩散法检测药敏结果。结果神经外科ICU菌群主要以革兰阴性杆菌(71.6%)为主,鲍曼不动杆菌占16.7%,大肠埃希菌占15.7%,铜绿假单胞菌占13.7%,肺炎克雷伯菌占13.7%等。但葡萄球菌、粪肠球菌等阳性球菌(28.4%)也有增加的趋势。亚胺培南和头孢哌酮/舒巴坦仍保持最高抗菌活性,细菌的耐药率分别为15.3%和30.6%。结论我院神经外科ICU感染主要病原菌是革兰阴性杆菌,对常用抗菌药物耐药性较高,但革兰阳性球菌所占比例呈增高趋势。控制第二、三代头孢菌素以及制酸剂(质子泵抑制剂)的预防性用药,减少耐药菌株的产生,有针对性地使用抗生素是控制危重病人感染的有效措施。     

大黄素和小剂量雌激素合用对去卵巢大鼠骨质疏松的预防作用

目的观察大黄素和小剂量雌激素联合应用对去卵巢大鼠骨质疏松的预防作用.方法3月龄大鼠双侧卵巢去除术后预防用药90 d.用骨组织形态计量学方法,测定大鼠胫骨近端松质骨静态参数和动态参数,观察骨物理生长指标、血清生化指标和器官指数.结果大黄素90 mg·kg-1·d-1和己烯雌酚5 μg·kg-1·d-1联合应用可抑制去卵巢大鼠的破骨细胞活性,完全对抗其骨转化率增高和骨量丢失的骨质疏松症状,与己烯雌酚30 μg·kg-1·d-1的作用相当,且降低己烯雌酚对子宫和肝脏的刺激作用.结论大黄素和小剂量己烯雌酚联合应用可预防去卵巢大鼠骨质疏松.     

外科重症病人脑电双频指数指导靶控输注咪达唑仑的镇静效果

目的评价外科重症监护病房(SICU)病人脑电双频指数(BIS)指导靶控输注(TCI)咪达唑仑的镇静效果。方法SICU病人30例,随机分为3组(n=10):A组采用恒速输注咪达唑仑0．06 mg·kg-1·h-1镇静;B组采用咪达唑仑TCI镇静,初始血浆靶浓度为60 ng/ml;C组在BIS指导下咪达唑仑TCI镇静,初始血浆靶浓度为60 ng／ml。每30 min采用Ramsay镇静评分评估镇静深度,若Ramsay镇静评分小于或大于4分,则A组输注速率增加或减少0．02 mg·kg-1·h-1,B组血浆靶浓度增加或减少20 ng／ml。C组若BIS大于或小于70,则血浆靶浓度增加或减少20 ng／ml。B、C组均随机抽取30份2 ml动脉血样,测定咪达唑仑血药浓度,用偏离性和精密度评价TCI系统的性能。结果咪达唑仑TCI系统的偏离性为12．5％,精密度为22．5％。咪达唑仑实测血药浓度与Ramsay镇静评分的相关系数为0．67(P<0．05)。镇静过程中C组Ramsay镇静评分4分所占比例(54％)高于A组(28％)和B组(40％)(P<0．01)。结论咪达唑仑TCI系统的性能可靠,用于SICU病人以BIS为70调控咪达唑仑TCI,可产生良好的镇静效果。     

土壤环境基因组技术及其在新药发现中的应用

土壤是微生物最重要的生境，土壤微生物具有极大的多样性。然而传统培养技术只能得到约1％的微生物纯培养，其余都是未被纯培养微生物。利用土壤环境基因组技术，可以把未被纯培养微生物的基因克隆到载体中并在宿主中进行表达，获得比已培养微生物丰富的代谢产物多样性，这为我们发现新颖结构先导化合物以及新药开辟了新的道路。本文介绍应用环境基因组技术构建土壤DNA文库的思路和方法。