387例病残儿死亡原因分析

为探讨病残儿死亡原因,提出干预措施,对1992—2005年在本院死亡的387例病残儿病例进行了回顾性分析。结果表明,入住本院的病残儿主要死亡原因前三位分别是出生缺陷、脑瘫和感染性疾病,死亡年龄以3岁以下病残儿为主,占87.59%。提示加强优生优育的健康教育,注意孕妇孕期和围产期保健,减少出生缺陷和脑瘫的发生率,是降低病残儿死亡率的关键。     

低温煤焦油中压气相固定床加氢的研究

提出了一个煤焦油热加工-中压固定床气相加氢的加工方法以制取液体燃料及酚类.并根据这个方法在本院自制的5871号催化剂上进行了初步研究,作了物料平衡、催化剂活性、寿命及再生等试验.催化剂寿命良好,再生后活性可以恢复.     

物理化学实验安全教育实践探索*

安全教育是化学实验教学的重要组成部分, 针对本院物理化学实验存在的安全隐患,提出了以实验安全告知书等形式对学生进行安全教育。通过网络视频、操作指南、周知卡片以及知晓单等形式告知实验中可能存在的安全隐患、突发事件的急救措施等,提高学生的安全意识和对事故的应变能力,强化学生的安全操作能力,确保实验安全有序进行。     

锌在儿童保健中的作用初探

任意以参加本院保健的３００例儿童,参照缺锌儿童和健康儿童的发锌数据,进行了缺锌儿童治疗后的跟踪调查以及临床诊断。结果表明,年龄越小,发锌低于正常值的越多;体格达标,发锌低于正常值的儿童中,有较大一部分无锌缺乏的表现,其机体内处于严临床缺锌状态。     

构建培养民族师范生的"5+2+1"化学实验教学体系

基于民族地区师范生基础薄弱和特殊需求,结合本院的实际情况,构建了＂5＋2＋1＂化学实验教学体系。     

183例肺结核合并感染病人合理用药分析

考察了肺结核合并感染病人合理用药情况。随机抽取本院2000年度183例肺结核合并感染病例,进行用药分析。结果表明,大多数用药合理,不合理用药主要有快整型杀菌型与快速型抑菌剂的合用（13例,7．1％）;具有较强耳毒性和肾毒性的链霉素和阿米卡星使用频度最高;三联用药率为61．75％。     

巩固爱婴医院成果的几点体会

为响应世界卫生组织（WHO）和联合国儿童基金会（UNICEF）发起的“创建爱婴医院”的行动号召，以实际行动实现我国政府对世界卫生组织的承诺，广州市第六人民医院于1996年4月份开始创建爱婴医院，经过职工共同努力，8月份就顺利通过了市、省两级“爱婴医院”的评审，正式获得了“爱婴医院”的光荣称号。1997年5月份，国家级评审小组对本院进行了严格的复评，对本院坚持母乳喂养工作给予了肯定。现将该工作的体会总结如下。1领导重视，是对坚持母乳喂养工作的有力支持本院领导十分重视创建爱婴医院的工作，专门成立了由院领导亲自挂帅的…     

68例智力低下儿童发病原因与发铅含量关系探讨

对本院遗传优生门诊１９９４年以来确诊为６８例智力低下儿童进行了发铅测定。其中１２人发铅明显超过正常值,占总数的１７．６％。发铅增高的１２人中,有５人为神经系统病变,１人为射材矮小,另外６例无明显医学原因。本组病例显示,铅对儿童的神经系统损害较明显。讨论了防止胎儿和儿童受铅毒害的措施。     

在有机化学实验中设置计算化学模块

计算化学快速发展,对于化学研究有非常强的指导作用,因此将其引入本科低年级实验教学很有必要。本文在调研国内外高校计算化学课程开设情况的基础上,根据本院学生特点和课程的需要,在面向大一本科生的核心实验课程——有机化学实验中引入了计算模块。模块设计从实验问题出发,将计算项目和实验紧密结合,采用分层次教学的模式进行。利用Canvas线上教学平台对微课、讲义、作业、测验等学习资源进行有效组织,通过直播课和微信群进行讨论和答疑,以翻转课堂的形式进行混合式教学,取得了很好的教学效果。     

现阶段中小型医院放射信息系统组建构想

为解决中小型医院资金短缺难以实现影像数字化的问题,提出了单独设计RIS软件包的构想。该构想能体现自家优势,适应本院工作流程,方便科室医生使用,工作效率得到了很大提高。     

Liposomes as Antibiotic Delivery Systems: A Promising Nanotechnological Strategy against Antimicrobial Resistance

Antimicrobial drugs are key tools to prevent and treat bacterial infections. Despite the early success of antibiotics, the current treatment of bacterial infections faces serious challenges due to the emergence and spread of resistant bacteria. Moreover, the decline of research and private investment in new antibiotics further aggravates this antibiotic crisis era. Overcoming the complexity of antimicrobial resistance must go beyond the search of new classes of antibiotics and include the development of alternative solutions. The evolution of nanomedicine has allowed the design of new drug delivery systems with improved therapeutic index for the incorporated compounds. One of the most promising strategies is their association to lipid-based delivery (nano)systems. A drug’s encapsulation in liposomes has been demonstrated to increase its accumulation at the infection site, minimizing drug toxicity and protecting the antibiotic from peripheral degradation. In addition, liposomes may be designed to fuse with bacterial cells, holding the potential to overcome antimicrobial resistance and biofilm formation and constituting a promising solution for the treatment of potential fatal multidrug-resistant bacterial infections, such as methicillin resistant Staphylococcus aureus. In this review, we aim to address the applicability of antibiotic encapsulated liposomes as an effective therapeutic strategy for bacterial infections.     

A novel mechanism of antibiotic resistance: study of the complex state of peptides with bacterial Staphylococcus aureus ribosomes

Two antibiotic resistance peptides, the E-peptide (MRLFV) and the K-peptide (MRFFV) conferring macrolide and ketolide resistance, respectively, were studied in the complex state with bacterial Staphylococcus aureus ribosomes after a conformational analysis by NMR spectroscopy and molecular modeling of the unbound molecules. T2 (CPMG) measurements were used to characterize equilibrium binding of antibiotic resistance peptides to bacterial ribosomes. Additionally, interactions of antibiotic resistance peptide to ribosomes were investigated using two-dimensional transferred nuclear Overhauser effect spectroscopy (TRNOESY), resulting in bound structures compatible with the experimental NMR data.     

Chip-calorimetric evaluation of the efficacy of antibiotics and bacteriophages against bacteria on a minute-timescale

Rapid detection of antibiotic resistances of clinical bacterial strains would allow an early selective antibiotic therapy and a faster intervention and implementation of infection control measurements. In clinical practice, however, conventional antibiotic susceptibility tests of bacteria often need 24 h until the results are obtained. The metabolic heat production of bacteria is an excellent possibility to record their physiological activities and could therefore be used for a rapid discrimination of bacterial strains which are resistant or non-resistant to antibiotics and also to lytic bacteriophages, respectively. Unfortunately, conventional calorimeters suffer from need of comparably large volumes of bacterial suspensions are characterised by slow operation and high costs which restrict their application in clinical laboratories. The present paper demonstrates that a new type of calorimeters developed on silicon-chip technology enables the detection of antibiotic resistances on a minute-timescale. For this reasons, a prototype chip calorimeter was used which sensitivity is 20 nW related to the heat production of about 10⁴ bacteria. For a clear discrimination of antibiotic resistance about 10⁵ bacteria are required. The antibiotic resistances and susceptibilities of different strains of Staphylococcus aureus to cefoxitin and the sensitivities of S. aureus DSM 18421 and E. coli DSM 498 to a mixture of two bacteriophages were studied. Comparing the heat productions of cultures incubated with antibiotics or bacteriophages to those without these antibacterial preparations enabled a clear discrimination of resistant and non-resistant strains already after totally 2 h.     

Strong Antibiotic Activity of the Myxocoumarin Scaffold in vitro and in vivo

The increasing emergence of resistances against established antibiotics is a substantial threat to human health. The discovery of new compounds with potent antibiotic activity is thus of utmost importance. Within this work, we identify strong antibiotic activity of the natural product myxocoumarin B from Stigmatella aurantiaca MYX-030 against a range of clinically relevant bacterial pathogens, including clinical isolates of MRSA. A focused library of structural analogs was synthesized to explore initial structure-activity relationships and to identify equipotent myxocoumarin derivatives devoid of the natural nitro substituent to significantly streamline synthetic access. The cytotoxicity of the myxocoumarins as well as their potential to cure bacterial infections in vivo was established using a zebrafish model system. Our results reveal the exceptional antibiotic activity of the myxocoumarin scaffold and hence its potential for the development of novel antibiotics.     

Synergistic Antibacterial and Antibiofilm Effect Between (+)-Medioresinol and Antibiotics In Vitro

In this study, antibacterial effects of (+)-Medioresinol isolated from stem bark of Sambucus williamsii and its synergistic activities in combination with antibiotics such as ampicillin, cefotaxime, and chloramphenicol were tested by antibacterial susceptibility testing and checkerboard assay. (+)-Medioresinol possessed antibacterial effects against antibiotics-susceptible- or antibiotics-resistant strains. Most of combinations between (+)-Medioresinol and each antibiotic showed synergistic interaction (fractional inhibitory concentration index ≤0.5) against bacterial strains including antibiotics-resistant Pseudomonas aeruginosa. Furthermore, the antibiofilm effect of (+)-Medioresinol alone or in combination with each antibiotic was investigated. The results indicated that not only (+)-Medioresinol but also its combination with each antibiotic had antibiofilm activities. It concludes that (+)-Medioresinol has potential as a therapeutic agent and adjuvant for treatment of bacterial infection.     

Exploring the use of conformationally locked aminoglycosides as a new strategy to overcome bacterial resistance

The emergence of bacterial resistance to the major classes of antibiotics has become a serious problem over recent years. For aminoglycosides, the major biochemical mechanism for bacterial resistance is the enzymatic modification of the drug. Interestingly, in several cases, the oligosaccharide conformation recognized by the ribosomic RNA and the enzymes responsible for the antibiotic inactivation is remarkably different. This observation suggests a possible structure-based chemical strategy to overcome bacterial resistance; in principle, it should be possible to design a conformationally locked oligosaccharide that still retains antibiotic activity but that is not susceptible to enzymatic inactivation. To explore the scope and limitations of this strategy, we have synthesized several aminoglycoside derivatives locked in the ribosome-bound "bioactive" conformation. The effect of the structural preorganization on RNA binding, together with its influence on the aminoglycoside inactivation by several enzymes involved in bacterial resistance, has been studied. Our results indicate that the conformational constraint has a modest effect on their interaction with ribosomal RNA. In contrast, it may display a large impact on their enzymatic inactivation. Thus, the work presented herein provides a key example of how the conformational differences exhibited by these ligands within the binding pockets of the ribosome and of those enzymes involved in bacterial resistance can, in favorable cases, be exploited for designing new antibiotic derivatives with improved activity in resistant strains.     

Polypept(o)ide-based bactericides: weapons against antibiotic-resistant bacterial infections

Emerging antibiotic resistance in bacterial pathogens has necessitated the development of alternative ‘outside of the box’ antimicrobial therapeutics. Polypept(o)ide-based bactericides with chemical structures mimicking antimicrobial host defense peptides have emerged as promising candidates for treating antibiotic-resistant and recurring infections. This review summarizes the recent advances in membrane-active polypept(o)ide-based bactericides in the treatment of antibiotic-resistant bacterial infections associated with the physical disruption of bacterial cell walls/cell membranes. Among these polypept(o)ide-based bactericides, nonantibiotic treatment strategies are employed to combat lethal bacterial strains resulting from acquired antibiotic resistance and biofilm formation, featuring the capacity to evade acquired antibiotic resistance-related mechanisms and to alleviate the emergence of drug resistance. Emphasis will focus on the typical polypept(o)ides with diverse molecular conformations (e.g., linear, brush-like, and star-shaped) and various chemical structures of monomers (e.g., α-amino acid, β-amino acid, and N-substituted glycine) that are central to the performance of antimicrobial polypept(o)ides. Finally, a brief discussion of the key challenges and prospects of polypept(o)ide-based bactericides is presented.     

Enzyme‐Responsive Polymeric Vesicles for Bacterial‐Strain‐Selective Delivery of Antimicrobial Agents

Antimicrobial resistance poses serious public health concerns and antibiotic misuse/abuse further complicates the situation; thus, it remains a considerable challenge to optimize/improve the usage of currently available drugs. We report a general strategy to construct a bacterial strain‐selective delivery system for antibiotics based on responsive polymeric vesicles. In response to enzymes including penicillin G amidase (PGA) and β‐lactamase (Bla), which are closely associated with drug‐resistant bacterial strains, antibiotic‐loaded polymeric vesicles undergo self‐immolative structural rearrangement and morphological transitions, leading to sustained release of antibiotics. Enhanced stability, reduced side effects, and bacterial strain‐selective drug release were achieved. Considering that Bla is the main cause of bacterial resistance to β‐lactam antibiotic drugs, as a further validation, we demonstrate methicillin‐resistant S. aureus (MRSA)‐triggered release of antibiotics from Bla‐degradable polymeric vesicles, in vitro inhibition of MRSA growth, and enhanced wound healing in an in vivo murine model.     

Digital Quantification of DNA Replication and Chromosome Segregation Enables Determination of Antimicrobial Susceptibility after only 15 Minutes of Antibiotic Exposure

Rapid antimicrobial susceptibility testing (AST) would decrease misuse and overuse of antibiotics. The “holy grail” of AST is a phenotype‐based test that can be performed within a doctor visit. Such a test requires the ability to determine a pathogen's susceptibility after only a short antibiotic exposure. Herein, digital PCR (dPCR) was employed to test whether measuring DNA replication of the target pathogen through digital single‐molecule counting would shorten the required time of antibiotic exposure. Partitioning bacterial chromosomal DNA into many small volumes during dPCR enabled AST results after short exposure times by 1) precise quantification and 2) a measurement of how antibiotics affect the states of macromolecular assembly of bacterial chromosomes. This digital AST (dAST) determined susceptibility of clinical isolates from urinary tract infections (UTIs) after 15 min of exposure for all four antibiotic classes relevant to UTIs. This work lays the foundation to develop a rapid, point‐of‐care AST and strengthen global antibiotic stewardship.     

Bacterial protein secretion — a target for new antibiotics?

The heavy use of antibiotics over recent decades has resulted in widespread resistance of bacteria to many drugs. Overcoming resistance requires new approaches to antibiotic development, including the exploitation of new targets in the bacterial cell. Protein secretion is essential for bacterial cell growth and virulence, so it could be a suitable target for new therapeutic agents.