Lysosomal enzyme cathepsin D protects against alpha-synuclein aggregation and toxicity

α-synuclein (α-syn) is a main component of Lewy bodies (LB) that occur in many neurodegenerative diseases, including Parkinson's disease (PD), dementia with LB (DLB) and multi-system atrophy. α-syn mutations or amplifications are responsible for a subset of autosomal dominant familial PD cases, and overexpression causes neurodegeneration and motor disturbances in animals. To investigate mechanisms for α-syn accumulation and toxicity, we studied a mouse model of lysosomal enzyme cathepsin D (CD) deficiency, and found extensive accumulation of endogenous α-syn in neurons without overabundance of α-syn mRNA. In addition to impaired macroautophagy, CD deficiency reduced proteasome activity, suggesting an essential role for lysosomal CD function in regulating multiple proteolytic pathways that are important for α-syn metabolism. Conversely, CD overexpression reduces α-syn aggregation and is neuroprotective against α-syn overexpression-induced cell death in vitro. In a C. elegans model, CD deficiency exacerbates α-syn accumulation while its overexpression is protective against α-syn-induced dopaminergic neurodegeneration. Mutated CD with diminished enzymatic activity or overexpression of cathepsins B (CB) or L (CL) is not protective in the worm model, indicating a unique requirement for enzymatically active CD. Our data identify a conserved CD function in α-syn degradation and identify CD as a novel target for LB disease therapeutics.     

Letrozole as primary therapy for endometrial hyperplasia in young women.

OBJECTIVE: To study letrozole as a primary therapeutic agent for endometrial hyperplasia with or without atypia in young women. METHODS: Five premenopausal women presenting for infertility were diagnosed as having endometrial hyperplasia. A second biopsy was performed after they were treated for 3 months with 2.5 mg of letrozole per day. Serum levels of estradiol and progesterone were measured each month. RESULTS: Curettage of the endometrium at the end of treatment revealed no evidence of endometrial hyperplasia or atypia in any of the patients. Low serum levels of estradiol were found in all patients. CONCLUSION: This case series indicates that aromatase inhibitors deserve attention for the conservative treatment of endometrial hyperplasia. However, more studies are needed to confirm the efficacy and safety of this agent.     

河北省高等医学院校临床教学基地现状与建设对策研究

结合本省高等医学院校教学基地评审工作,对临床教学工作存在的问题进行了剖析,其问题主要表现在:(1)院校双方缺乏必要的联系和沟通,临床教学中出现的问题不能及时得到解决.(2)盲目扩大临床教学基地,良莠兼收,临床教学质量无法保证.(3)一些教学医院承担教学任务不堪重负,临床教学在低水平状态下惰性运转.(4)带教教师素质不高,无法完成正常的临床教学任务.(5)受多种因素制约,学生的临床实践能力得不到锻炼.针对存在问题,提出以下对策和建议:(1)行政主管部门科学合理地规划高校临床教学基地.(2)建立临床带教教师培训基地,提高带教水平,优化临床带教队伍.(3)统一临床实习教学计划和大纲,规范临床教学和管理工作.(4)加强临床教学工作和管理经验的交流.     

银耳多糖铁(Ⅲ)配合物的合成及其理化性质的研究

用从银耳中提取的多糖和 FeCl_3为主要原料合成一种新的补铁剂——银耳多糖铁(Ⅲ)配合物(ITC),并测定了其理化性质。实验证明:在 ITC 水溶液中,不存在游离 Fe~(3+),表明铁(Ⅲ)与银耳多糖形成了稳定的配合物.经红外光谱、超速离心及电镜观测可知:银耳多糖铁(Ⅲ)配合物是以β-(FeOOH)。为微核,银耳多糖在其核表面络合而形成的表面配合物,其粒子直径约为30～80 nm,属于高分子化合物。ITC 在生理 pH 下不沉淀、不水解,可望有较好的生物利用度.     

益肾固泉液抗利尿作用研究

用代谢笼法观测了益肾固泉液对正常大鼠、水负荷大鼠和加用利尿药大鼠的尿量 ,用火焰光度法测定尿中K 、Na ;用硫氰酸比色法测尿中Cl 。结果益肾固泉液对正常大鼠 2 4小时尿量无影响 ,10g/kg益肾固泉液显著减少水负荷大鼠 1小时尿量 ;2 0 g/kg对水负荷大鼠 1小时、4小时、6小时尿量和总尿量均比对照组显著减少 ;10g/kg、2 0 g/kg对加用利尿药安体舒通的大鼠有明显的抗利尿作用。益肾固泉液对水负荷大鼠尿中K 的排出明显多于对照组 ,对Na 、Cl 的排出量无显著影响。上述结果表明益肾固泉液对正常大鼠无抗利尿作用 ,对水负荷大鼠和加用利尿药大鼠均有明显抗利尿作用     

肾移植术后并发泌尿系统肿瘤的相关因素与临床干预

目的:探讨肾移植术后并发泌尿系统肿瘤的相关因素与临床干预措施.方法:报告9例(10次)此种患者的临床资料.9例肾移植术后均行免疫抑制治疗.肿瘤均发生在自体肾、输尿管和膀胱:肾透明细胞癌、肾肉瘤和膀胱腺癌各1例,肾盂输尿管膀胱移行细胞癌6例,其中1例先发生膀胱腺癌后又发生肾盂输尿管移行细胞癌.肿瘤发生于移植术后8～146个月,且8例发生在应用新型免疫抑制剂之后.患者均有服用龙胆泻肝丸或冠心苏合丸史.8例接受了根治性手术,1例未能手术切除.结果:9例随访8～44个月,未能手术切除1例于术后5个月肝转移死亡.1例肉瘤复发后放弃治疗后死亡.1例膀胱肿瘤复发,行膀胱全切腹壁造瘘术,1例腺癌已出现肺和胸膜转移.另5例最后随访时存活良好.结论:肾移植术后并发泌尿系统肿瘤以移行细胞癌为多;可能与服用含马兜铃的中药和应用新型免疫抑制剂有关;根治性手术治疗、减少免疫抑制剂用量和更换免疫抑制剂种类是主要临床干预措施.     

用海伦娜（Helena）报告生成语言优化海伦娜电泳仪报告

介绍ＨＲＧＬ的结构和相应细节。在此基础上分析和实现了对报告打印的优化。     

市场经济条件下医院工作者应确立的几个观念

根据课题研究，结合卫生工作实际，笔者认为，在市场经济条件下，应紧密围绕市场经济规律，正确确立战略性观念，市场性观念，变革性观念，竞争性观念，服务性观念，经营性观念，及时获取并使用信息的观念等，通过转变观念及其对内含的理解，提高卫生服务的质量，推进卫生事业的发展。     

老年高血压病患者血清可溶性白介素2受体与临床分期相关性的观察

目的探讨老年高血压病患者血清中可溶性白介素－２受体（ｓＩＬ－２Ｒ）的水平，并比较老年高血压病不同临床分期的ｓＩＬ－２Ｒ变化。方法采用双抗体夹心（ＥＬＩＳＡ）法，对４６例老年高血压病人血清ｓＩＬ－２Ｒ的水平，与３０例正常人（ＮＣ）进行检测对比，并对其老年高血压病患者不同临床分期的ｓＩＬ－２Ｒ的水平进行观察。结果老年高血压病患者ｓＩＬ－２Ｒ水平明显高于对照组（Ｐ＜０．０１）；且随临床分期的增加而增高（Ｐ＜０．０１），有明显的正相关性。结论老年高血压病患者体内存在有免疫功能系乱，导致ｓＩＬ－２Ｒ的增高。ｓＩＬ－２Ｒ可作为临床观察老年高血压病的细胞免疫功能及病情判定的有效指标。