483例烧伤所致工伤患者的流行病学分析

目的为临床研究和工伤预防提供有效的烧伤流行病资料。方法回顾性分析2010年1月至2012年12月期间我院收治工伤职工中的483例烧伤患者,分析其性别和年龄分布、单位性质、工伤职工职业分布、劳动强度差异、防护情况、受伤情况、诊治经过和转归情况。结果工伤职工中烧伤患者男女比例为5.71∶1,中青年占据的比例最高。私营企业的工伤职工最多。大部分患者来自于一线工作岗位,病因多为火焰、热物体、电及热液;其预防、急救措施存在着不足。患者住院日期长、治疗费用高、转归情况较差。结论发生在工作中的烧伤防护不足、后果严重,需要加强安全宣传、完善保护措施及有关部门的监管力度。     

空心螺钉治疗锁骨骨折的生物力学研究

目的检测直径6.5 mm空心螺钉固定锁骨骨折的生物力学性能,并与钢板螺钉内固定方法进行比较,为临床应用提供依据。方法采集10个成人锁骨标本,行中外1/3处锁骨横形骨折模型,随机分二组,分别采用空心螺钉和钢板螺钉内固定,测试各组的三点弯曲应变及轴向挤压效应。结果轴向挤压实验：载荷1571 N时,钢板固定组螺钉发生松动,在载荷2470.13 N时钢板固定失败,而锁骨空心螺钉固定失败载荷为3034.99 N,两者相差明显。三点弯曲实验：无论钢板组的正向（270.29-254.38 N）或负向加压负荷（425.85-443.76 N）结果均远远小于空心螺钉组（1017.16-1103.39 N）。结论直径6.5 mm空心螺钉治疗锁骨骨折从生物力学上来看,在抗轴向负荷及三点弯曲负荷上均优于目前常规使用的钢板螺钉。     

某院校护理专业学生实验室生物安全知识认知情况调查分析

目的 通过对柳州市2所医学院校护理专业学生的问卷调查,了解护理专业学生对实验室生物安全知识的认知情况及态度.方法 运用随机抽样的方法,采用问卷调查方式对护理专业502人开展问卷调查.结果 学生对医院内感染、消毒、灭菌的概念掌握较好,对实验室生物安全、生物危害的等级分类、气溶胶、生物安全柜等知识的了解程度有限.结论 护理专业学生对实验室生物安全知识的了解程度有待提高,学校应加强实验室生物安全教育.     

Random sparse sampling strategy using stochastic simulation and estimation for a population pharmacokinetic study

The purpose of this study was to use the stochastic simulation and estimation method to evaluate the effects of sample size and the number of samples per individual on the model development and evaluation. The pharmacokinetic parameters and inter- and intra-individual variation were obtained from a population pharmacokinetic model of clinical trials of amlodipine. Stochastic simulation and estimation were performed to evaluate the efficiencies of different sparse sampling scenarios to estimate the compartment model. Simulated data were generated a 1000 times and three candidate models were used to fit the 1000 data sets. Fifty-five kinds of sparse sampling scenarios were investigated and compared. The results showed that, 60 samples with three points and 20 samples with five points are recommended, and the quantitative methodology of stochastic simulation and estimation is valuable for efficiently estimating the compartment model and can be used for other similar model development and evaluation approaches.     

Synthesis and structure–activity relationship of nuciferine derivatives as potential acetylcholinesterase inhibitors

Acetylcholinesterase inhibitors (AChEIs) are currently the best available pharmacotherapy for Alzheimer patients, but because of bioavailability issues, there is still great interest in discovering better AChEIs. The aporphine alkaloid is an important class of natural products, which shows diverse biological activity, such as acetylcholinesterase inhibitory activity. To find new lead AChEIs compounds, eight aporphine alkaloids were synthesized by O-dealkylation, N-dealkylation, and ring aromatization reactions using nuciferine as raw material. The anti-acetylcholinesterase activity of synthesized compounds was measured using modified Ellman’s method. The results showed that some synthesized compounds exhibited higher affinity to AChE than the parent compound nuciferine. Among these compounds, 1,2-dihydroxyaporphine (2) and dehydronuciferine (5) were the most active compounds (IC₅₀ = 28 and 25 μg/mL, respectively). Preliminary analysis of structure–activity relationships suggested that aromatization of the C ring, the presence of the alkoxyl group at C1 and the hydroxy group at C2 position as well as the alkyl substituent at the N atom were favorable to the acetylcholinesterase inhibition. Molecular docking was also applied to predict the binding modes of compounds 1, 2, and 9 into the huperzine A binding site of AChE.     

Development of a Method That Eliminates False-Positive Results due to Nerve Growth Factor Interference in the Assessment of Fulranumab Immunogenicity

Fulranumab, a human IgG2 monoclonal antibody that neutralizes nerve growth factor (NGF), is currently in development for the treatment of pain. Our initial immunogenicity test method was found to be prone to NGF interference, leading to a high apparent incidence of anti-drug antibody (ADA) in phase 1 studies. The ADA immunoassay comprised a homogeneous bridging electrochemiluminescence (ECL) format with biotin and ruthenium-labeled fulranumab bound together (“bridged”) by ADA in test samples for detection. In this assay, NGF produced a false-positive signal due to its ability to bridge fulranumab molecules. Thus, we developed a specificity assay to eliminate the NGF false-positive results. We encountered the challenge of eliminating drug interference as well as drug target interference, and discovered that the acid-dissociation-based pretreatment of samples used for mitigating drug interference dramatically increased drug target interference. Several strategies were investigated to eliminate the NGF interference; yet only one strategy specifically removed NGF and produced true fulranumab-specific ADA results by using competitive inhibition with fulranumab and utilizing an alternative NGF binding antibody to eliminate NGF interference. Using this new method, we confirmed that the high apparent anti-fulranumab antibody incidence (>60%) in clinical study samples was in fact due to fulranumab-bound NGF released during the acid-dissociation step of the ADA testing method. We conclude that our revised method accurately identifies anti-fulranumab antibodies by incorporating steps to eliminate fulranumab and NGF interference. We advise that acid-dissociation pretreatment must not be universally applied to improve ADA assays without investigating its bioanalytical risks versus benefits.