糖尿病病人胰岛素泵应用及相关知识调查

[目的]探讨糖尿病病人应用胰岛素泵强化治疗的相关知识及需求情况.[方法]采用自行设计的问卷调查表,对60例糖尿病胰岛素泵强化治疗病人进行调查.[结果]病人对胰岛素泵了解甚少,相关知识缺乏,希望接受胰岛素泵知识教育.[结论]胰岛素泵应用现状存在较多问题,影响病人血糖的良好控制,应提高病人对胰岛素泵的认可程度和依从性,提高生活质量.     

国外医院绩效评价对我国的启示

绩效评价是促进公立医院公益性、引导其医疗服务质量持续改进的有效方法。然而目前国内尚无一套统一、科学、合理的公立医院绩效考核制度, 对医改背景下的公立医院绩效进行考核, 已成为困扰我国卫生事业发展的重要问题。本文在借鉴国外医院绩效评价先进经验措施的基础上, 结合我国现状, 对医院绩效评价提出了一些针对性的建议和意见。     

Acute toxicity is a dose-limiting factor for intravenous polymyxin B: A safety and pharmacokinetic study in healthy Chinese subjects

ObjectivesPolymyxin B is a last-line antibiotic for multidrug-resistant gram-negative bacterial infections. However, limited safety and pharmacokinetic information is available. We investigated the safety and pharmacokinetics of intravenous polymyxin B in healthy subjects.MethodsAn open-label, single-dose clinical trial was conducted in healthy Chinese subjects. Polymyxin B (sulphate) was administered intravenously at 0.75 or 1.5 mg/kg (n = 10 per dose, 5 males and 5 females) to examine the safety and pharmacokinetics.ResultsOne female subject in the 1.5-mg/kg group discontinued due to abdominal pain during administration. The most frequently reported adverse events were perioral paraesthesia, dizziness, and numbness of extremities (7/10 subjects in the 0.75-mg/kg group, all subjects in the 1.5-mg/kg group). All neurotoxicity-related events dissipated without treatment within a maximum of 23 h. Notably, abdominal pain (3/5) and vulvar pruritus (2/5), colpitis (2/5) or abnormal uterine bleeding (1/5) were reported in female subjects receiving the 1.5-mg/kg dose. In the 0.75-mg/kg group, the total clearance, volume of distribution and half-life of polymyxin B were 0.028±0.002 L/h/kg, 0.219±0.023 L/kg and 5.44±0.741 h, respectively; similar values were observed in the 1.5-mg/kg group. Urinary recovery was 3.7 ± 1.1% and 8.1 ± 1.3% in the 0.75- and 1.5-mg/kg groups, respectively. Population pharmacokinetics of polymyxin B was consistent with a three-compartment model. The clearance and distribution of the central compartment were 0.027 L/h/kg and 0.071 L/kg, respectively.ConclusionsThis study is the first to examine the safety and pharmacokinetics of polymyxin B in healthy subjects. Our results highlight that acute toxicity is a dose-limiting factor for intravenous polymyxin B.     

Ca2+-binding activity of a COOH-terminal fragment of the Drosophila BK channel involved in Ca2+-dependent activation

Mutational and biophysical analysis suggests that an intracellular COOH-terminal domain of the large conductance Ca(2+)-activated K(+) channel (BK channel) contains Ca(2+)-binding site(s) that are allosterically coupled to channel opening. However the structural basis of Ca(2+) binding to BK channels is unknown. To pursue this question, we overexpressed the COOH-terminal 280 residues of the Drosophila slowpoke BK channel (Dslo-C280) as a FLAG- and His(6)-tagged protein in Escherichia coli. We purified Dslo-C280 in soluble form and used a (45)Ca(2+)-overlay protein blot assay to detect Ca(2+) binding. Dslo-C280 exhibits specific binding of (45)Ca(2+) in comparison with various control proteins and known EF-hand Ca(2+)-binding proteins. A mutation (D5N5) of Dslo-C280, in which five consecutive Asp residues of the "Ca-bowl" motif are changed to Asn, reduces (45)Ca(2+)-binding activity by 56%. By electrophysiological assay, the corresponding D5N5 mutant of the Drosophila BK channel expressed in HEK293 cells exhibits lower Ca(2+) sensitivity for activation and a shift of approximately +80 mV in the midpoint voltage for activation. This effect is associated with a decrease in the Hill coefficient (N) for activation by Ca(2+) and a reduction in apparent Ca(2+) affinity, suggesting the loss of one Ca(2+)-binding site per monomer. These results demonstrate a functional correlation between Ca(2+) binding to a specific region of the BK protein and Ca(2+)-dependent activation, thus providing a biochemical approach to study this process.     

Transgenic alteration of Toll immune pathway in the female mosquito Aedes aegypti

Reverse genetics is a powerful tool for understanding gene functions and their interactions in the mosquito innate immunity. We took the transgenic approach, in combination with the RNA interference (RNAi) technique, to elucidate the role of mosquito REL1, a homolog of Drosophila Dorsal, in regulation of Toll immune pathway in the mosquito Aedes aegypti. By transforming the mosquitoes with DeltaREL1-A or a double-stranded RNA construct of REL1 driven by the female fat body-specific vitellogenin (Vg) promoter with the pBac[3xP3-EGFP, afm] vector, we generated two different transgenic mosquito strains, one with overexpressed AaREL1 and the second with AaREL1 knockdown. Both strains had a single copy of the respective transgene, and the expression in both transgenic mosquitoes was highly activated by blood feeding. Vg-DeltaREL1-A transgenic mosquitoes activate Toll immune pathway in the fat body by blood feeding. The overexpression of both isoforms, AaREL1-A and AaREL1-B, in Vg-DeltaREL1-A transgenic mosquitoes resulted in the concomitant activation of Aedes Sp?tzle1A and Serpin-27A, independent of septic injury. The same phenotype was observed in the mosquitoes with RNAi knockdown of an Aedes homolog to Drosophila cactus, an IkappaB inhibitor of Drosophila Toll pathway. The effect of the transgenic RNAi knockdown of AaREL1 on mosquito innate immunity was revealed by increased susceptibility to the entomopathogenic fungus Beauveria bassiana and the reduced induction of Spz1A and Serpin-27A gene expression after fungal challenge. These results have proven that AaREL1 is a key downstream regulator of Toll immune pathway in the mosquito A. aegypti.     

卫生化学实验“理论-实验一体化”教学改革实践

本研究探讨了“理论-实验一体化”特色型教学改革在卫生化学实验教学中的应用效果。通过将理论和实验课程统一打包安排,将理论与实验内容进行模块整合,开展多种形式的教学。实践表明,“理论-实验一体化”教学改革实践对提高卫生化学实验课程的教学质量,培养学生的综合素质方面有重要理论及实践意义。     

Daptomycin therapy in 6 cases of left-sided infective endocarditis and literature review北大核心CSCD

Objective To evaluate the efficacy of daptomycin in the treatment of left-sided infective endocarditis after failing to respond to vancomycin. Methods A retrospective analysis was conducted for 6 cases of infective endocarditis. Results Five of the six infective endocarditis patients were complicated with paravalvular abscess (artificial valve in 3 cases, native valve in 2 cases). Their disease deteriorated even under vancomycin treatment. Four of these patients received emergency valve replacement surgery but still febrile after operation. The antimicrobial therapy was switched to daptomycin at dose of 6 mg/kg daily for 2 to 4 weeks. The patients responded satisfactorily to daptomycin. The infection was controlled to some extent in the fifth patient after switching to daptomycin, but recurred later, and died suddenly on day 21 after reoperation. The sixth patient had infective endocarditis of native valve, and had treated with piperacillin-tazobactam for 2 weeks and vancomycin for 3 weeks, but responded poorly. The patient still had fever and enlarged vegetation. Switching to daptomycin reduced the body temperature and vegetation. Serum creatine kinase elevated moderately in one patient, and normal in the other 5 patients. No other apparent adverse reaction was reported. One patient died and the other five patient survived well for 18 months to 5 years. Conclusions Preliminary observation demonstrates the efficacy of daptomycin salvage treatment in a few cases of left-sided infective endocarditis after failing to respond to vancomycin therapy. © 2018, Editorial Department of Chinese Journal of Infection. All rights reserved.     

热带假丝酵母菌临床分离株毒力表型特征研究

目的 描述临床分离的热带假丝酵母菌培养不同时间的天冬氨酰蛋白酶活性(蛋白酶活性)、磷脂酶活性和溶血活性,并分析不同感染部位分离菌的蛋白酶活性和溶血活性差异。方法 将分离自不同感染部位的热带假丝酵母菌鉴定后分别接种在牛血清蛋白培养基、卵黄琼脂培养基和羊血琼脂培养基上,培养不同时间(24、48和72 h)后检测蛋白酶活性、磷脂酶活性和溶血活性。结果 热带假丝酵母菌培养24、48和72 h时均具有蛋白酶活性和溶血活性,但未表现出磷脂酶活性;热带假丝酵母菌在48 和72 h时的蛋白酶活性高于其在24 h时的活性,在72 h范围内,溶血活性随培养时间延长持续增长;分离自不同感染部位的热带假丝酵母菌的蛋白酶活性(P=0.368)和溶血活性(P=0.985)差异无统计学意义。结论 我国热带假丝酵母菌临床分离株培养不同时间具有蛋白酶活性和溶血活性,但无磷脂酶活性。