生物等效性试验中受试者食用高脂餐的调查研究

目的评价餐后生物等效性试验中受试者食用高脂餐的情况,总结高脂餐食谱制订的考虑因素。方法对完成首都医科大学附属北京朝阳医院Ⅰ期临床试验研究室(以下简称"本中心")两周期、双交叉、餐后生物等效性试验的33例健康受试者的高脂餐食谱、就餐时间、进食量进行分析,对食用西式高脂餐的21例受试者进行就餐感受的问卷调查,调查内容包括食用高脂餐的感受、餐后饱腹感、餐后有无不适、对于中西式高脂餐的选择和对西式高脂餐中接受度不高的成分。结果本中心选择的中式、西式高脂餐对于受试者的进食量均无影响;57. 14%的受试者倾向于食用西式高脂餐,42. 86%的受试者倾向于食用中式高脂餐;西式高脂餐中接受度不高的成分主要有黄油(33. 33%)、纯牛奶(14. 29%)、沙拉酱(14. 29%)、美式培根(9. 52%)。结论本中心选择的中西式高脂餐基本满足试验需要。综合考虑指导原则要求、受试者就餐感受、避免接受度不高的食物成分等因素,制订更为合理的高脂餐食谱,从而提高临床试验质量。     

注射用重组人血清白蛋白-人粒细胞集落刺激因子(Ⅰ)融合蛋白在健康受试者的耐受性研究

目的评价重组(酵母分泌型)人血清白蛋白-人粒细胞集落刺激因子(Ⅰ)融合蛋白在健康受试者的耐受性和安全性。方法将26例健康受试者(男女各半)按先后顺序入组,进行4个剂量组试验(150,300,500,650μg·kg^-1),每组分别入组4,6,8,8例。根据体重计算给药剂量,受试者于给药当天上臂三角肌部位皮下注射给药1次。用药后观察药物不良事件(AE),定时进行实验室检查、心电图检查。结果共25例受试者发生AE,共145例次。150,300,500及650μg·kg^-1剂量组的AE分别为13,11,56和65例次。其中134例次考虑与研究药物相关。常见的AE有骨痛、单核细胞计数升高、血碱性磷酸酶升高、头痛、高尿酸血症、血乳酸脱氢酶升高、脾肿大、肌肉疲劳。研究中未出现AE导致的用药暂停、受试者退出或试验提前中止。未发生严重不良事件(SAE)。未发生剂量限制性毒性。结论注射用重组(酵母分泌型)人血清白蛋白-人粒细胞集落刺激因子(Ⅰ)融合蛋白在中国健康受试者中单次给药150,650μg·kg^-1剂量范围内有较好的安全性,本临床试验未探索到健康人群的最大耐受剂量。     

Enhancing patient research partner engagement: Research in psoriatic arthritis

The perspective from individuals with psoriatic arthritis (PsA) can be beneficial to PsA research, increasing the likelihood that the results are meaningful and relevant to PsA patients. While there has been an advancement of patient research partner (PRP) involvement in PsA research over time, the effort is still in its infancy. Measures to ensure PRP engagement (PRPE) occurs and its impact evaluated need to be implemented routinely to increase PRPE in PsA research.     

Reduced variability in tacrolimus pharmacokinetics following intramuscular injection compared to oral administration in cynomolgus monkeys: Investigating optimal dosing regimens

Tacrolimus is one of the most commonly used immunosuppressive agents in animal models of transplantation. However, in these models, oral administration is often problematic due to the lowered compliance associated with highly invasive surgery and due to malabsorption in the intestinal tract. Therefore, we carried out a study to determine the pharmacokinetics of tacrolimus after intramuscular (IM) injection and to determine the optimal IM dosing regimens in primate models. Six male cynomolgus monkeys (Macaca fascicularis) were used in the study. Doses of 0.1 mg/kg and 5 mg were administered via IM injection and oral administration, respectively, once to determine single-dose pharmacokinetics and once daily for 5 days to determine multiple-dose pharmacokinetics. According to pharmacokinetic model estimates, the inter- and intra-individual variabilities in bioavailability following IM injection were remarkably reduced compared with those following oral administration. Monte Carlo simulations revealed that C_peak, C_trough and AUC would also have less variability following IM injection compared with oral administration. In this study, we found that the pharmacokinetic characteristics of tacrolimus were more constant following IM injection compared with oral administration. These results suggest that IM injection can be an alternative route of administration fin non-human primate model studies.     

Pharmacokinetic and pharmacodynamic study of a clinically effective anti-CD2 monoclonal antibody

The humanized IgG1κ monoclonal antibody siplizumab and its rat parent monoclonal IgG2b antibody BTI-322 are directed against the CD2 antigen. Siplizumab is species-specific, reacting with human and chimpanzee cells but not with cells from any other species, including other non-human primates. Because siplizumab treatment has recently shown great potential in clinical transplantation, we now present the results of our previous pharmacokinetic, pharmacodynamic and safety studies of both antibodies. Fourteen chimpanzees received 1-3 doses of 0.143 to 5.0 mg/kg iv The effects were followed with flow cytometry on peripheral lymphocytes and staining of lymph nodes. Side effects were recorded. Serum antibody concentrations were followed. Across the doses, a rapid, transient depletion of CD2, CD3, CD4 and CD8 lymphocytes and NK cells was observed for both antibodies. Immune reconstitution was more rapid for BTI-322 compared to siplizumab. Paracortical lymph node T cell depletion was moderate, estimated at 45% with doses of >0.6 mg/kg. Restoration of lymph node architecture was seen after two weeks to two months for all animals. All four subjects receiving BTI-322 experienced AEs on the first dosing day, while the eight subjects dosed with siplizumab experienced few mild, transient AEs. Infusion with siplizumab and BTI-322 resulted in rapid depletion of CD2⁺ cells in circulation and tissue. Siplizumab had a longer t_1/2 and fewer AEs compared to BTI-322.     

The accuracy of diagnostic tests for adenoid hypertrophy: A systematic review

BackgroundAdenoid hypertrophy may cause sleep-disordered breathing and altered craniofacial growth. The authors conducted a study to gauge the accuracy of alternative tests compared with nasoendoscopy (reference standard) for screening adenoid hypertrophy.MethodsThe authors conducted a systematic review that included searches of electronic databases, hand searches of bibliographies of relevant articles and gray literature searches. They included all articles in which an alternative test was compared with nasoendoscopy in children with suspected nasal or nasopharyngeal airway obstruction.ResultsThe authors identified seven articles that were of poor to good quality. They identified the following alternative tests: multirow detector computed tomography (sensitivity, 92 percent; specificity, 97 percent), videofluoroscopy (sensitivity, 100 percent; specificity, 90 percent), rhinomanometry with decongestant (sensitivity, 83 percent; specificity, 83 percent) and clinical examination (sensitivity, 22 percent; specificity, 88 percent). Lateral cephalograms tended to have good to fair sensitivity (typically 61-75 percent) and poor specificity (41-55 percent) when adenoid size was evaluated but excellent to good specificity when airway patency was evaluated (68-96 percent).ConclusionsNo ideal tool exists for dentists to screen adenoid hypertrophy, owing to access constraints, radiation concerns and suboptimal diagnostic accuracy. Research is needed to identify a low-risk, easily acceptable, highly valid diagnostic screening tool.Practical ImplicationsAlthough lateral cephalograms (which have good to fair sensitivity) and a thorough medical history (which has good specificity) are imperfect individually, when they are used together, they can compensate for each other's weaknesses. This combined approach is the best tool available to dentists for screening adenoid hypertrophy.     

北京市体检人群EB病毒联合抗体检测结果分析

目的通过分析3项EB病毒(EBV)抗体联合检测结果,了解体检人群EB病毒感染情况,为鼻咽癌早期筛查提供技术支持。方法选取2017年1月1日—2018年6月30日在北京航天总医院健康管理中心进行EBV(Rta)-IgG、衣壳抗原(VCA)-IgA、早期抗原(EA)-IgA 3种抗体联合检测的体检人员共4251名,采用SPSS 16.0软件进行统计分析。结果4251名受检者中3种EBV抗体单项阳性率的比较差异有统计学意义(χ2=12.465,P=0.000),阳性率由高至低的顺序依次为VCA-IgA、EA-IgA、Rta-IgG;不同性别间VCA-IgA阳性率男性高于女性(P=0.000);不同年龄组3种EBV抗体阳性率总体随年龄增长而增高,EA-IgA(P=0.000)及Rta-IgG(P=0.0038)在不同年龄组中阳性率有显著差异,在61岁以上的受检者中EA-IgA和Rta-IgG阳性率最高,分别为6.3%及3.7%,VCA-IgA在51岁以上的受检者中阳性率最高;92.9%的受检者3项检测均为阴性,1项阳性者占6.4%,2项阳性者占0.7%,未发现3项阳性者;抗体阳性检测结果男性与女性聚集情况比较无差别,抗体检出阳性受检者在耳鼻喉科检查发现鼻炎、鼻窦炎及其他异常比例较高。结论3种EBV抗体的阳性率与性别和年龄都有一定的关系,50岁以上的人群应作为重点筛查对象。EBV抗体联合检测阳性受检者推荐鼻咽镜检查,为鼻咽癌的早期筛查提供依据。     

护理学专业本科学科建设的发展现状和对策

介绍了国外和国内护理本科教育现状;指出目前我国护理本科的学科建设存在对学科建设认识不够、缺乏高水平的学术梯队、科学研究相对薄弱、学科建设经费不足等问题,影响和制约护理学科建设的开展;认为高等护理院校可通过立足学校实际,不断强化学科建设意识,突出特色,重点攻关,以课题带动学科建设等途径开展护理本科学科建设。     

论文被引频次学科领域百分位在创建期刊百分位数指标中的应用

【目的】 探讨基于InCites数据库中论文被引频次百分位创建期刊百分位数指标的方法,比较不同百分位数指标的期刊评价效果。【方法】 以2018年版JCR中多学科交叉科学期刊及其2017—2018年发表的论文为研究对象,根据InCites数据库中论文被引频次学科领域百分位(Percentile in Subject Area,PSA)创建期刊百分位数指标(Journal Indicator of Percentage Rank,JIPR),包括JIPR4、JIPR6、JIPR8、JIPR10、JIPR100和平均PSA(aPSA),比较不同JIPR对多学科交叉科学期刊的评价效果。【结果】 68种期刊的JIPR4呈偏态分布,其他JIPR呈正态分布,多数指标之间呈高度相关,不同等级JIPR之间相关度更高;影响因子与aPSA排序位次变化较大的期刊多是发表综述文献较多、单篇高被引论文对影响因子贡献较大的期刊。【结论】 与影响因子相比,多数JIPR有明显优势,其中aPSA可能是最理想的期刊评价指标。     

Microvascularisation of lips in ageing edentulous subjects

Macroscopic changes of the lips in the edentulous elderly subject are accompanied by variations in their microvascularisation. This study was undertaken on histological or clarified sections from totally edentulous subjects whose vascular system was injected with Indian ink agar. A reduction in density and size of the superficial (papillary or mucosal) and deep (reticular or submucosal) networks is observed with age. These changes are to be seen in relation to imaging and to the reduction in occlusal potential of the lips.