基础医学综合实验与实验设计课程教学改革实践

本着以课程为中心的原则，研究组在基础医学综合实验课程建设、运行方式、教学方法改革等方面积极探索；以联系疾病、联系应用为导向，广泛开展基于疾病动物模型制备及干预过程的实验教学；增加"创新性"实验项目，确保课程内容体现出前沿性和时代性；以生物医学前沿方法训练引领课程建设，着力培养学员的学习能力、实践能力和创新能力。此外，在优化以实践应用、创新性为导向的课程内容建设的基础上，打造虚拟仿真实验项目，尝试线上线下混合式教学，全方位提升学员的实践运用能力。     

黄芪丹参对多囊卵巢综合征大鼠雄激素/胰岛素受体表达影响的研究

目的：研究黄芪联合丹参对多囊卵巢综合征（PCOS）模型大鼠雄激素(AR)及胰岛素受体（INSR）表达的影响。方法：通过对大鼠注射外源性雄激素建立高雄激素无排卵模型，将建模成功的大鼠随机分为黄芪组、丹参组、黄芪＋丹参联合组以及模型组，每组10只，分别以黄芪、丹参、黄芪＋丹参联合用药行不同干预治疗，模型组用生理盐水灌胃。比较各组大鼠血清雄激素、胰岛素水平；卵巢AR、INSR mRNA及蛋白水平。结果：1）与模型组比较，黄芪组血清睾酮水平明显下降，丹参组血清胰岛素水平明显下降；联合组血清睾酮及胰岛素水平均明显下降。2）与模型组比较，黄芪组INSR蛋白水平明显下降，丹参组INSR蛋白水平明显上升；黄芪＋丹参联合组AR蛋白水平明显下降，同时INSR蛋白水平明显升高。3）与模型组比较，黄芪组AR mRNA水平明显下降，丹参组INSR mRNA水平明显上升；黄芪＋丹参联合组AR mRNA水平明显下降，同时卵巢INSR mRNA水平明显升高。结论：黄芪可改善PCOS的高雄激素状态，丹参可改善PCOS的高胰岛素状态，联合用药兼具抗雄激素及降低胰岛素的作用，AR、INSR表达的改变是其可能的作用机制之一。     

166Ho-DOTMP radiation-absorbed dose estimation for skeletal targeted radiotherapy.

166Ho-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene-phosphonate (DOTMP) is a tetraphosphonate molecule radiolabeled with 166Ho that localizes to bone surfaces. This study evaluated pharmacokinetics and radiation-absorbed dose to all organs from this beta-emitting radiopharmaceutical. METHODS: After two 1.1-GBq administrations of 166Ho-DOTMP, data from whole-body counting using a gamma-camera or uptake probe were assessed for reproducibility of whole-body retention in 12 patients with multiple myeloma. The radiation-absorbed dose to normal organs was estimated using MIRD methodology, applying residence times and S values for 166Ho. Marrow dose was estimated from measured activity retained after 18 h. The activity to deliver a therapeutic dose of 25 Gy to the marrow was determined. Methods based on region-of-interest (ROI) and whole-body clearance were evaluated to estimate kidney activity, because the radiotracer is rapidly excreted in the urine. The dose to the surface of the bladder wall was estimated using a dynamic bladder model. RESULTS: In clinical practice, gamma-camera methods were more reliable than uptake probe-based methods for whole-body counting. The intrapatient variability of dose calculations was less than 10% between the 2 tracer studies. Skeletal uptake of 166Ho-DOTMP varied from 19% to 39% (mean, 28%). The activity of 166Ho prescribed for therapy ranged from 38 to 67 GBq (1,030-1,810 mCi). After high-dose therapy, the estimates of absorbed dose to the kidney varied from 1.6 to 4 Gy using the whole-body clearance-based method and from 8.3 to 17.3 Gy using the ROI-based method. Bladder dose ranged from 10 to 20 Gy, bone surface dose ranged from 39 to 57 Gy, and doses to other organs were less than 2 Gy for all patients. Repetitive administration had no impact on tracer biodistribution, pharmacokinetics, or organ dose. CONCLUSION: Pharmacokinetics analysis validated gamma-camera whole-body counting of 166Ho as an appropriate approach to assess clearance and to estimate radiation-absorbed dose to normal organs except the kidneys. Quantitative gamma-camera imaging is difficult and requires scatter subtraction because of the multiple energy emissions of 166Ho. Kidney dose estimates were approximately 5-fold higher when the ROI-based method was used rather than the clearance-based model, and neither appeared reliable. In future clinical trials with 166Ho-DOTMP, we recommend that dose estimation based on the methods described here be used for all organs except the kidneys. Assumptions for the kidney dose require further evaluation.     

外伤脱位牙的临床研究

目的研究脱位牙的临床治疗、治疗效果及其影响因素.病人和方法98例牙脱位患者,根据不同情况进行适当处理,然后进行复位、即刻牙再植、牙弓夹板固定等治疗;通过牙髓活力检查、X片检查,随访观察治疗后的临床效果及牙齿愈合情况.结果部分脱位的73颗牙,复位后全部保存,术后随访无临床症状,X线检查未发现牙根吸收及周围骨质丧失;全脱位的25颗牙,进行牙再植后,除2例外,均获得成功保留.结论部分脱位牙应在局麻下进行复位、固定;完全脱位牙齿应作牙再植术.     

耳穴脉冲刺激对Oddi括约肌张力及肌电活动的影响

目的　探讨耳穴脉冲电刺激治疗胆石症 ,胆绞痛的机制 .方法　选用 15条成年杂种犬 ,进行耳穴体表脉冲刺激与缩胆素 (CCK)对在体狗胆囊张力 ,Oddi括约肌张力及肌电活动影响的对比研究 .结果　耳穴脉冲电刺激对胆囊张力无明显影响 [(1.2 7± 0 .2 6 ) k Pa与 (1.2 4± 0 .2 2 ) k Pa,P<0 .0 5 ],CCK注射液能明显提高胆囊张力 [(1.2 7± 0 .2 6 ) k Pa与 (1.91± 0 .39) k Pa,P<0 .0 5 ],CCK注射液能明显降低Oddi括约肌张力 [(2 .2 4± 0 .5 5 ) k Pa与 (1.5 8± 0 .5 6 ) k Pa,P>0 .0 5 ]及肌电活动 .结论　耳穴脉冲电刺激同 CCK一样 ,均对 Oddi括约肌的张力有显著的降低作用 ,并减少 Oddi括约肌的肌电峰电位爆发波的频率与电压值 ,推测其对胆绞痛有治疗作用 ,并有助于胆结石的排石过程 .     

人体蠕形螨的生物学研究

用透明胶带法观察蠕形螨在人体面部的寄生、逸出及其在体外的存活能力。结果表明：毛囊蠕形螨（Ｄｅｍｏｄ－ｅｘｆｏｌｉｃｕｌｏｒｕｍ，Ｄ．ｆ．）主要以颚体朝向毛囊底部寄生，且常常有多条群居现象，而皮脂蠕形螨，（Ｄｅｍｏｄｅｘｂｒｅｖｉｓ，Ｄ．ｂ．）一般为单条独居生活。两种人体蠕形螨昼夜均可主动爬出毛囊口出现在皮肤表面，Ｄ．ｆ．以白天１０００～１８００为逸出高峰；Ｄ．ｂ．则以夜间２２００～２００逸出最多。此外，蠕形螨在体外有较强的活动力和存活力。透明胶带法在人体蠕形螨的流行病学调查和生物学研究方面具有较高的应用价值     

精索静脉曲张患者精索静脉和外周血睾酮水平的对照研究

目的：探讨精索静脉血张患者血浆睾酮水平的变化及其机制。方法：对25例精索静脉曲张患者与22例腹股沟斜疝患者精索静脉和外周血睾酮水平进行对照研究。结果：精索静脉曲张组外周血睾酮浓度与腹股沟斜疝组无差别（P＞0．05），而精索静脉血睾酮浓度两组则有明显差异，精索静脉曲张组精索静脉血中睾酮浓度较腹股沟斜疝组低（P＜0．05）。结论：多种因素可影响外周血睾酮浓度，使其难以准确地反映睾丸分泌睾酮的实际水平，而精索静脉血中的睾酮浓度则能较为直接地反映睾丸的睾酮分泌能力。     

长期培养的大鼠原代肝细胞功能和形态学观察

目的：研究大鼠原代肝细胞长期体外培养后功能和形态的变化。 方法： 采用两步胶原酶原位灌流法分离大鼠肝细胞，并用Percoll分离液进行密度梯度离心进一步纯化肝细胞，采用0.4%台盼蓝染色观察细胞活力。然后将细胞接种于HepatoZYME-SFM培养基中培养，定期收集肝细胞培养液上清检测丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶（AST）、白蛋白、尿素氮的水平。采用乙氧基试卤灵O-脱乙基酶活性（EROD）方法检测肝细胞P450的CYPⅠA1功能。 结果： 新鲜分离的大鼠肝细胞总数（2-3）×108cells/whole liver，Percoll分离液纯化后活力和纯度在90%以上。HepatoZYME-SFM培养下肝细胞生长良好并保持正常形态。AST、ALT水平在培养3 d后下降显著，6-9 d后趋于相对稳定的低水平。白蛋白的分泌功能、尿素合成能力在18 d内维持在较高水平。可在3-6 d检测到CYPⅠA1酶活性。 结论： Percoll液纯化新分离肝细胞可提高其活率和纯度，HepatoZYME-SFM培养条件下肝细胞可有效保持良好形态结构和一定的生物合成代谢能力，适合肝细胞的体外长期培养和功能研究。