Recent advances in preclinical in vitro approaches towards quantitative prediction of hepatic clearance and drug-drug interactions involving organic anion transporting polypeptide (OATP) 1B transporters

Hepatic uptake mediated by organic anion transporting polypeptide (OATP) 1B1 and 1B3 can serve as a major elimination pathway for various anionic drugs and as a site of drug-drug interactions (DDIs). This article provides an overview of the in vitro approaches used to predict human hepatic clearance (CL_h) and the risk of DDIs involving OATP1Bs. On the basis of the so-called extended clearance concept, in vitro–in vivo extrapolation methods using human hepatocytes as in vitro systems have been used to predict the CL_h involving OATP1B-mediated hepatic uptake. CL_h can be quantitatively predicted using human donor lots possessing adequate OATP1B activities. The contribution of OATP1Bs to hepatic uptake can be estimated by the relative activity factor, the relative expression factor, or selective inhibitor approaches, which offer generally consistent outcomes. In OATP1B1 inhibition assays, substantial substrate dependency was observed. The time-dependent inhibition of OATP1B1 was also noted and may be a mechanism underlying the in vitro–in vivo differences in the inhibition constant of cyclosporine A. Although it is still challenging to quantitatively predict CL_h and DDIs involving OATP1Bs from only preclinical data, understanding the utility and limitation of the current in vitro methods will pave the way for better prediction.     

基于响应面法优选美洲大蠊口腔原位温敏凝胶的制备研究

目的制备美洲大蠊Periplaneta americana口腔原位温敏凝胶。方法采用自由基聚合法首次以N-异丙基丙烯酰胺(NNIPAM)和甲基丙烯酸羟丙酯(HPMA)合成聚(N-异丙基丙烯酰胺-甲基丙烯酸羟丙酯)[P(NNIPAM-HPMA)]作为温敏材料;通过冷溶法制备美洲大蠊口腔原位温敏凝胶,采用Box-Behnken设计响应面法,以溶蚀时间、胶凝时间为评价指标,在固定美洲大蠊提取物用量基础上,对羟丙基甲基纤维素(HPMC)、聚乙烯吡咯烷酮(PVP K30)、P(NNIPAM-HPMA)的用量进行优选。结果通过原位聚合法合成了P(NNIPAM-HPMA)温敏材料;并用响应面法优选了可用于口腔的美洲大蠊原位温敏凝胶的处方,优选的处方为美洲大蠊提取物10%、HPMC 3.0%、PVP K30 9.5%、P(NNIPAM-HPMA) 10.0%,其溶蚀时间为2 h,胶凝时间8～9 s。结论优选得到美洲大蠊口腔原位温敏凝胶,为美洲大蠊提取物的口腔原位局部的临床应用奠定了科学依据。     

培养医学生岗位胜任力，推进临床教学改革

以加强医学本科教育,培养具备较高素质和较强岗位胜任力的医学专业人才为目的,紧紧围绕医学生岗位胜任力这个中心,契合学校医学人才培养目标,进行临床医学专业本科课堂教学改革的探索和研究。通过提高思想认识,发现存在的问题,更新教学理念,改进教学手段,整合利用资源,合理应用信息化教学手段、调整教学评价体系等一系列措施,以突出素质和能力培养为抓手,以期达到提高课堂教学效率,提升教师教学能力,激发学生自主学习能力和拓宽学生国际视野的结果,对全面提高临床医学教学质量、打造具有区域特色的高水平本科教育、全面提高医学人才培养水平有着重要意义。     

老年轻度认知障碍患者血清瘦素、甲状腺激素水平与局部脑血流量关系的研究

目的 通过检测老年轻度认知障碍（MCI）患者血清瘦素（LEP）、甲状腺激素水平，分析其与局部脑血流量（rCBF）的关系。方法 选择本院收治的128 例老年MCI 患者，另选健康者128 例作为对照组。检测血清LEP、甲状腺激素、大脑各区域rCBF 水平并分析其相关性。结果 老年MCI 组患者左右侧额叶、右侧颞叶、左侧顶叶、左右侧基底节区域脑血流量[（43.81±8.62）mL/（100 g·min）、（43.24±7.93）mL/（100 g·min）、（45.14±6.98）mL/（100 g·min）、（45.86±6.77）mL/（100 g·min）、（67.95±8.52）mL/（100 g·min）、（68.36±8.34）mL/（100 g·min）]低于对照组[（46.39±8.31）mL/（100 g·min）、（46.52±8.56）mL/（100 g·min）、（47.37±7.04）mL/（100 g·min）、（48.25±6.98）mL/（100 g·min）、（70.34±8.96）mL/（100 g·min）、（70.58±8.57）mL/（100 g·min）]（P＜0.05）。老年MCI 组患者血清LEP、T3、FT3 水平[（4.87±1.56）μg/L、（1.21±0.16）nmol/L、（3.04±0.36）pmol/L]低于对照组[（11.45±3.92）μg/L、（1.68±0.21）nmol/L、（4.82±1.21）pmol/L]（P＜0.05），TSH 水平为（2.78±0.75）IU/mL，高于对照组的（1.13±0.38）IU/mL（P＜0.05）。老年MCI 患者血清LEP 水平与左侧额叶、右侧颞叶、左侧顶叶rCBF 呈正相关（r=0.452、0.537、0.544，P 均＜0.05），T3 水平与左侧额叶、右侧颞叶rCBF 呈正相关（r=0.427、0.521，P 均＜0.05），FT3 水平与右侧颞叶rCBF 呈正相关（r=0.492，P＜0.05），TSH 水平与左侧额叶、右侧颞叶rCBF 呈负相关（r=-0.463、-0.489，P 均＜0.05）。结论 老年MCI 患者血清中LEP、T3、FT3 水平降低，TSH 水平升高，且与不同区域rCBF 有相关性，可通过调控脑血管功能影响rCBF 变化水平。     

住院医师规范化培训中引入Mini-CEX的实践

目的　观察对住院医师规范化培训部分学员使用Mini-CEX进行临床教学的效果。方法选取我院2015级住培学员40名，随机分为对照组和实验组，每组20人。2015年10月至2018年4月，对照组采用传统教学；实验组在传统教学基础上结合Mini-CEX活动，实验组每人在每个轮转科室至少进行2次Mini-CEX。毕业时应用改良的Mini-CEX评分量表、病例答辩和OSCE三种考核方法对两组学员进行测评。针对实施过Mini-CEX的教师和学员分别发放问卷，进行满意度调查。采用SPSS 18.0对数据进行统计分析，组间比较采用独立样本t检验，组内前后比较采用配对样本t检验。结果 Mini-CEX测评显示，两组学员各项临床能力毕业成绩均高于入学成绩，实验组学员毕业成绩优于对照组，实验组学员成绩提高分数大于对照组提高分数，差异均有统计学意义（P＜0.05）。病例答辩显示，实验组学员平均成绩为（81.16±3.75）分，优于对照组的（70.13±3.88）分，差异有统计学意义（t= -9.140，P=0.000）。OSCE考核显示，实验组平均总分为（96.300±4.681），优于对照组的（91.775±3.227）分，差异有统计学意义（t=-3.559，P=0.001）。共发放调查问卷80份，其中教师40份、学员40份，结果显示教师满意率达95.0%、学员满意率达92.5%。结论　Mini-CEX应用于住院医师规范化培训临床带教中，有利于提高学员的临床思维、医患沟通和人文关怀能力。     

Patterns of facial fractures in children

Morbidity and mortality among children is usually the result of trauma. Because a child’s face is retruded relative to the protecting skull, has a thicker layer of adipose tissue, more elastic bones, flexible sutures lines, the presence of tooth buds within the jaws, and the lack of pneumatisation of the sinuses, the facial bones fracture less commonly than in adults. Our aim was to assess the patterns of such fractures in children who presented to the department of Oral and Maxillofacial Surgery, King Edward Medical University/Mayo Hospital Lahore, Pakistan. All 535 eligible children between the ages of 1-16 years who presented during the two years December 2009 - December 2011 were included in the study. Facial fractures were diagnosed by clinical examination, plain radiographs, and computed tomography, and the pattern of fractures of the facial bones including the frontal bone, orbital bones, maxilla, zygoma, naso-orbito-ethmoidal complex, mandible, and dentoalveolar region was documented. The male:female ratio was 2:1 with 369 male (70%) and 166 female (31%) patients. Fall was the cause in 212 (39%), and in 167 (31%) it was road traffic accidents, while sports were the cause in 135 (25%). The naso-orboto-ethmoid complex was fractured in 37 cases (7%) while 104 children (19%) presented with isolated fractures of the zygomatic bone. The maxilla was fractured in 195 cases (36%), the mandible in 380 (71%), and dentoalveolar trauma was the cause in 256 (50%). The mandible was the bone that was most often fractured (mostly in boys and usually as a result of falls during summer vacations), with the peak occurring in those aged 8-12 years.