Acoustical enrichment during early postnatal development changes response properties of inferior colliculus neurons in rats

The structure and function of the auditory system may be influenced by acoustic stimulation, especially during the early postnatal period. This study explores the effects of an acoustically enriched environment applied during the third and fourth week of life on the responsiveness of inferior colliculus neurons in rats. The enrichment comprised a spectrally and temporally modulated complex sound reinforced with several target acoustic stimuli, one of which triggered a reward release. The exposure permanently influenced neuronal representation of the sound frequency and intensity, resulting in lower excitatory thresholds at neuronal characteristic frequency, an increased frequency selectivity, larger response magnitudes, steeper rate–intensity functions and an increased spontaneous activity. The effect was general and non‐specific, spanning the entire hearing range – no changes specific to the frequency band of the target stimuli were found. The alterations depended on the activity of animals during the enrichment – a higher activity of rats in the stimulus–reward paradigm led to more profound changes compared with the treatment when the stimulus–reward paradigm was not used. Furthermore, the exposure in early life led to permanent changes in response parameters, whereas the application of the same environment in adulthood influenced only a subset of the examined parameters and had only a temporary effect. These findings indicate that a rich and stimulating acoustic environment during early development, particularly when reinforced by positive feedback, may permanently affect signal processing in the subcortical auditory nuclei, including the excitatory thresholds of neurons and their frequency and intensity resolution.     

导道滑脱风险跟踪评估监控流程的设计及应用

目的规范预防导管滑脱管理,降低非计划拔管发生率。方法制定导管滑脱风险评估监控表和导管滑脱风险跟踪评估监控流程,将导管滑脱风险评估监控表和跟踪评估监控流程应用于临床并进行动态管理。结果实施后高危拔管患者非计划拔管发生率显著低于实施前(P0.05)。结论实施导管滑脱风险跟踪评估监控流程,能降低非计划拔管发生率。     

单节段棘突间动态稳定装置置入术后1年棘突骨质吸收现象及其风险因素

【摘要】 目的：研究单节段L4/5棘突间动态稳定装置（Wallis）置入术后1年的L4及L5棘突骨质吸收现象,并行多因素回归分析对可能的原因进行探讨。方法：回顾性研究我科2009年~2011年间行单节段L4/5 Wallis置入手术的患者,通过比较术后1年与术后1周时两组X线片上L4及L5棘突高度、长度及厚度的差异,将患者分为两组：骨质吸收组与非骨质吸收组。比较两组患者性别、年龄、BMI、是否吸烟、骨质疏松、手术时间、术中出血量、腰背肌肉锻炼、佩戴腰围时间、L4/5棘突间距、L4/5椎间隙高度及腰椎前凸角度,并于术前及术后1年通过腰椎MRI对腰椎间盘退变程度进行分级以及对症状进行VAS、JOA、ODI评分。应用卡方检验、T检验及二分类多因素回归分析进行统计分析。结果：完成随访患者44例,男24例,女20例,平均年龄42.7岁。有29例发生骨质吸收,女性16例,占55.2%,其中L4和L5同时发生骨质吸收者16例,以L4、L5棘突高度骨质吸收最为严重,骨吸收率分别为（16.28±1.46）%、（22.93±1.63）%。术前存在骨质疏松的患者共7例,均发生了骨质吸收。棘突骨质吸收的独立危险因素有BMI（OR：1.337,95% CI：1.048～1.705）,30°<术前腰椎前凸角≤40°（OR：8.953,95% CI：1.011～79.269）,40°<术前腰椎前凸角≤50°（OR：11.160,95% CI：1.112～111.961）,术前腰椎前凸角>50°（OR：11.718,95% CI：1.535～89.436）;两组患者MRI、VAS、JOA及ODI评分比较无显著统计学差异（P>0.05）。结论：棘突间弹性内固定装置Wallis置入术后1年可观察到棘突的骨质吸收现象,该现象较为普遍并存在一定规律,患者术前BMI及腰椎前凸角度是其独立风险因素,骨质疏松也是其可能的原因之一,但是该现象与术后症状是否缓解及影像学改变无显著关联。     

Bayesian random effects selection in mixed accelerated failure time model for interval‐censored data

In many medical problems that collect multiple observations per subject, the time to an event is often of interest. Sometimes, the occurrence of the event can be recorded at regular intervals leading to interval‐censored data. It is further desirable to obtain the most parsimonious model in order to increase predictive power and to obtain ease of interpretation. Variable selection and often random effects selection in case of clustered data become crucial in such applications. We propose a Bayesian method for random effects selection in mixed effects accelerated failure time (AFT) models. The proposed method relies on the Cholesky decomposition on the random effects covariance matrix and the parameter‐expansion method for the selection of random effects. The Dirichlet prior is used to model the uncertainty in the random effects. The error distribution for the accelerated failure time model has been specified using a Gaussian mixture to allow flexible error density and prediction of the survival and hazard functions. We demonstrate the model using extensive simulations and the Signal Tandmobiel Study^®. Copyright © 2013 John Wiley & Sons, Ltd.     

人参须根中皂苷类成分提取工艺的研究

目的:研究人参须根中皂苷类成分的最佳提取工艺。方法:比较了乙醇回流提取法和超声波提取法提取人参皂苷的差异。在此实验基础上,通过单因素实验和正交实验,筛选出超声波法从人参须根中提取皂苷类成分的最优提取工艺。结果:人参须根中皂苷类成分的最优提取条件为50%乙醇,提取2次,每次40min,提取温度40℃,料液比为1:20。结论:该提取方法操作简单,有效成分的提取率高。     

Pharmacokinetic aspects and in vitro–in vivo correlation potential for lipid-based formulations

Lipid-based formulations have been an attractive choice among novel drug delivery systems for enhancing the solubility and bioavailability of poorly soluble drugs due to their ability to keep the drug in solubilized state in the gastrointestinal tract. These formulations offer multiple advantages such as reduction in food effect and inter-individual variability, ease of preparation, and the possibility of manufacturing using common excipients available in the market. Despite these advantages, very few products are available in the present market, perhaps due to limited knowledge in the in vitro tests (for prediction of in vivo fate) and lack of understanding of the mechanisms behind pharmacokinetic and biopharmaceutical aspects of lipid formulations after oral administration. The current review aims to provide a detailed understanding of the in vivo processing steps involved after oral administration of lipid formulations, their pharmacokinetic aspects and in vitro in vivo correlation (IVIVC) perspectives. Various pharmacokinetic and biopharmaceutical aspects such as formulation dispersion and lipid digestion, bioavailability enhancement mechanisms, impact of excipients on efflux transporters, and lymphatic transport are discussed with examples. In addition, various IVIVC approaches towards predicting in vivo data from in vitro dispersion/precipitation, in vitro lipolysis and ex vivo permeation studies are also discussed in detail with help of case studies.KEY WORDS: Pharmacokinetics, Lipolysis, IVIVC, Efflux transporters, Lymphatic delivery, Food effectAbbreviations: ADME, absorption/distribution/metabolism/elimination; AUC, area under the curve; BCS, biopharmaceutics classification system; BDDCS, biopharmaceutics drug disposition classification system; CACO, human epithelial colorectal adenocarcinoma cells; C_max, maximum plasma concentration; CMC, critical micellar concentration; CYP, cytochrome; DDS, drug delivery systems; FaSSGF, fasted-state simulated gastric fluid; FaSSIF, fasted-state simulated intestinal fluid; FeSSIF, fed-state simulated intestinal fluid; GIT, gastrointestinal tract; IVIVC, in vitro in vivo correlation; LCT, long chain triglyceride; LFCS, lipid formulation classification system; log P, n-octanol/water partition coefficient; MCT, medium chain triglyceride; MDCK, Madin–Darby canine kidney cells; NCE, new chemical entity; P-app, apparent permeability; P-gp, permeability glycoprotein; SCT, short chain triglyceride; SEDDS, self-emulsifying drug delivery system; SIF, simulated intestinal fluid; SMEDDS, self-microemulsifying drug delivery system; SNEDDS, self-nanoemulsifying drug delivery system; Vit E, vitamin E     

改良的臂丛阻滞麻醉

目的 探讨解剖学对臂丛神经阻滞麻醉的影响,为临床研究及应用提供参考依据。方法 选取20具尸体,应用经改良的喙突下臂丛神经阻滞法入路定位,进行垂直穿刺,神经阻滞点采用蓝色染料标记,同时对神经集中部位与标记点进行解剖暴露,探查神经集中点和体表标志之间的解剖关系。结果 左侧集中部位上缘到锁骨下缘中点、胸锁关节下缘、肩峰及喙突下缘的距离分别为（3.62±0.24）cm、（10.39±0.25）cm、（6.67±0.18）cm及（2.80±0.19）cm;右侧集中部位上缘到锁骨下缘中点、胸锁关节下缘、肩峰及喙突下缘的距离分别为（4.24±0.27）cm、（11.10±0.28）cm、（6.35±0.19）cm及（3.03±0.15）cm。 结论 局部解剖学的应用提高臂丛神经阻滞的准确性,从而可提高臂丛神经阻滞麻醉的效果,为临床研究及应用提供参考依据。