Histomorphometry of bone marrow biopsies in primary osteomyelofibrosis/-sclerosis (agnogenic myeloid metaplasia) - correlations between clinical and morphological features

Summary Histomorphometry was performed on representative trephine biopsies of the bone marrow on admission of 50 patients (21 male, 29 female-age 67 years) with so-called primary osteomyelofibrosis/-sclerosis (OMF) not preceded by any other subtype of chronic myeloproliferative disorders. This study was firstly aimed at testing correlations between histological features (amount of haematopoiesis, cytological aspects of mega-karyocytes, density of reticulin and collagen fibres and degree of osteosclerosis) and laboratory data, as well as spleen size and duration of relevant prediagnostic symptoms. Secondly, we concentrated on a discrimination of OMF patients into two sub-groups according to bone marrow morphology and clinical variables. Statistical evaluation of histomorphometric variables and haematological findings disclosed that there was a progressive fibro-osteosclerotic process in the evolution of disease features. Increase in medullary fibrosis was significantly paralleled by an abnormal or pleomorphic megakaryopoiesis in the bone marrow: there was an increase in irregularity of perimeters for megakaryocytes and naked nuclei combined with smaller sizes of these elements including the nuclei. Additionally, there was a greater number of pycnotic bare nuclei. A number of morphometric features (density of fibres, degree of osteosclerosis, amount of haematopoiesis) were associated with corresponding clinical data (spleen size, length of preclinical history). By consideration of a set of basic histomorphometric variables our co-hort of 50 patients could be divided into an early hyperplastic subtype with no or minimal medullary reticulin and another group with conspicuous fibrotic and osteosclerotic alterations of the bone marrow. It was noticeable that we found no significant correlation between amount of haematopoiesis or marrow cellularity with splenomegaly. This result suggests that splenic haematopoiesis (myeloid metaplasia) may represent an autonomous or neoplastic process and not only compensation for a failing fibro-osteosclerotic bone marrow.Supported by a grant from the Deutsche Forschungsgemeinschaft (DFG-Th 390/1-1)     

儿童用药物非临床安全性评价

目前,主要是由成年动物和成人研究的安 全性资料支持儿童用药,但这并不足以能评估药物 对儿童人群特定发育过程中可能存在的影响,而且 有些影响难以在临床试验中或通过常规的上市后监 督来发现,因而需要进行幼年动物的非临床安全性 评价。本文参考FDA的相关指导原则,对幼年动物 安全性评价的一般性考虑、与临床研究对应的幼年 动物研究的时间安排、试验设计和评价等方面进行 讨论,以期为我国儿童用药物非临床安全性研究与 评价提供参考,为将来制定我国的相关指导原则积 累经验。     

食蟹猴静脉注射抗HER2人源化抗体急性毒性研究

目的 评价抗HER2 人源化抗体的急性毒性。方法 将食蟹猴随机分为4 组,包括溶媒对照和抗HER2 人源化抗体75、150 和250 mg/kg 组,单次iv 溶媒对照组或供试品,进行各项毒理学指标检测。结果 给药后各组动物临床症状、体质量、摄食量、体温、心电图、血压和血液学检测均未见明显异常;血清生化结果显示,150 mg/kg 组与250 mg/kg 组动物给药后血清IgG 水平出现一过性增加;各组动物均未见大体病理学改变。结论 食蟹猴单次iv 抗HER2 单抗,总体上动物具有良好的耐受性,最大耐受剂量可达250 mg/kg,这些结果为进一步临床前评价抗HER2 人源化单克隆抗体的安全性奠定了基础。     

纤维蛋白封闭剂对SD大鼠连续腹腔注射给药14天的毒性研究

目的 评价SD大鼠连续腹腔注射纤维蛋白封闭剂的安全性。方法 SD大鼠雌雄分别按体质量随机分4组,即空白对照组、纤维蛋白封闭剂低剂量组、中剂量组和高剂量组,每组20只,雌雄各半。3个给药组的给药剂量分别为85.5、171.0和342.0mg/kg,每天腹腔注射给药,连续14d,恢复期28d,进行一般症状、血液学、血液生化和病理组织学等指标检测。结果 与空白对照组相比,纤维蛋白封闭剂中、高剂量组大鼠第14天的白细胞计数显著升高,纤维蛋白原显著降低,中、高剂量组大鼠脾脏的脏器重量有增加趋势。组织病理学检查发现部分高剂量动物腹腔出现残留药物引起的纤维肉芽组织包裹。上述变化指标在恢复期结束时基本可恢复。结论大鼠腹腔注射纤维蛋白封闭剂85.5~342.0mg/kg,安全剂量为85.5mg/kg,毒性剂量为171.0mg/kg。毒性靶系统或靶部位为血液系统、免疫系统和给药局部,毒性作用可逆。     

阿尔茨海默病治疗药物的开发及探索

阿尔茨海默病（AD）是最常见的神经系统变性疾病,也是最常见的痴呆类型。胆碱酯酶抑制剂及N-甲基-D-天冬氨酸拮抗剂对轻中度AD有一定疗效,但效果较缓和且为对症治疗,寻找更有效的治疗药物势在必行。本文重点综述AD治疗药物的研发及临床前期的靶向干预策略。     

Living biobank-based cancer organoids: prospects and challenges in cancer research

Biobanks bridge the gap between basic and translational research. Traditional cancer biobanks typically contain normal and tumor tissues, and matched blood. However, biospecimens in traditional biobanks are usually nonrenewable. In recent years, increased interest has focused on establishing living biobanks, including organoid biobanks, for the collection and storage of viable and functional tissues for long periods of time. The organoid model is based on a 3D in vitro cell culture system, is highly similar to primary tissues and organs in vivo, and can recapitulate the phenotypic and genetic characteristics of target organs. Publications on cancer organoids have recently increased, and many types of cancer organoids have been used for modeling cancer processes, as well as for drug discovery and screening. On the basis of the current research status, more exploration of cancer organoids through technical advancements is required to improve reproducibility and scalability. Moreover, given the natural characteristics of organoids, greater attention must be paid to ethical considerations. Here, we summarize recent advances in cancer organoid biobanking research, encompassing rectal, gastric, pancreatic, breast, and glioblastoma cancers. Living cancer biobanks that contain cancerous tissues and matched organoids with different genetic backgrounds, subtypes, and individualized characteristics will eventually contribute to the understanding of cancer and ultimately facilitate the development of innovative treatments.     

基础医学课程整合对推进学生素质教育的意义探讨

文章就六门基础医学系统解剖学、组织胚胎学、生理学、病理学、病理生理学和药理学的课程整合,针对课程体系、教学内容、教学方法和手段、双语教学、实验和评价体系等的改革,探讨了整合课程对学生创新能力、知识积累、职业技能、思维辨析、团队协作精神等素质教育的积极影响和意义。     

“基础医学论坛活动”在本科生科研素质培养中的作用研究

尽早开展医学生的科研素质和实践能力培训是现代医学教育改革的一项重要任务。我们针对二年级部分医学类五年制本科生,连续8年开展了"基础医学论坛活动"。通过对本科生科研素质现状的调查分析,探讨培养医学本科生科研素质与创新能力的途径与对策。     

活血潜阳祛痰方干预高血压前临床心衰阶段的临床研究

目的:观察活血潜阳祛痰方干预高血压前临床心衰阶段患者的临床疗效。方法:纳入100例高血压前临床心衰阶段(阶段B)血瘀阳亢痰浊证患者,随机分为治疗组和对照组,每组各50例。对照组患者采用西医常规治疗,治疗组患者在西医常规治疗基础上加服活血潜阳祛痰方,两组治疗周期均为16周。比较两组患者的动态血压、中医症状积分,检测患者的胰岛素抵抗、心功能及心脏结构相关指标,包括空腹血糖(FPG)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)、脑钠肽(BNP)、室间隔厚度(IVST)、左心室后壁厚度(LVPWT)、左心室舒张末内径(LVEDD)、左心室质量指数(LVMI)及左心室射血分数(LVEF)。结果:①治疗后,两组患者的24 h、白天、夜间平均收缩压和舒张压均明显降低(P0.01),且治疗组患者的血压下降幅度较对照组更显著(P0.05,P0.01)。②治疗后,两组患者的中医症状积分均明显降低(P0.01),且治疗组患者的症状积分下降幅度大于对照组(P0.01)。③治疗后,两组患者的FIN、HOMA-IR水平均下降(P0.05,P0.01),且治疗组患者的FIN、HOMA-IR下降幅度大于对照组(P0.01)。④治疗后,两组患者的BNP水平均降低(P0.05,P0.01),且治疗组患者的BNP水平降低幅度大于对照组(P0.01);同时治疗组患者的LVEF水平有所升高(P0.05)。⑤治疗后,治疗组患者的LVEDD、IVST、LVPWT、LVMI均减小(P0.05,P0.01),对照组患者的LVEDD、IVST、LVMI亦减小(P0.05,P0.01),且治疗组患者的LVEDD、IVST、LVPWT、LVMI减小幅度均大于对照组(P0.05,P0.01)。结论:活血潜阳祛痰方结合西医常规疗法可降低高血压前临床心衰阶段血瘀阳亢痰浊证患者的血压,改善患者的胰岛素抵抗、左心室重构及心功能。