新鲜血小板与新鲜冰冻血小板膜活化糖蛋白的研究

目的通过对机采新鲜血小板与新鲜冰冻血小板在制备和贮存过程中血小板活化的状况来了解评估血小板输注的有效性。方法采用流式细胞技术观察有效期内新鲜血小板（22℃震荡保存7天内）与新鲜冰冻血小板（-80℃以下保存1年内）不同时段的膜糖化蛋白GPⅡb/Ⅲa和CD62P进行流式细胞分析。结果在-80℃保存12个月,其GPⅡb/Ⅲa和CD62P的表达差异无显著性,新鲜冰冻血小板CD62p的表达受到良好抑制,可与22℃振荡保存24 h的新鲜血小板质量相近;新鲜血小板在22℃条件下随保存时间的延长GPⅡb/Ⅲa和CD62P的表达迅速升高,与新鲜血小板相比48 h差异有显著性（P〈0.05）,72 h差异有极显著性（P〈0.01）。结论新鲜血小板冰冻期间发生的代谢损伤较常温条件下低。选择≤24 h的新鲜血小板用于一80℃冻存至少可以保存1年。     

Alcohol Modulation of Human Normal T-Cell Activation, Maturation, and Migration

We are interested in the characterization of the effects of alcohol on human T-cell activation, maturation, and migration, because this cell population is crucial in the initiation, regulation, and propagation of cellular immunity. We and others have described the effects of both acute and chronic exposure of human immune cells to ethanol (EtOH) in vitro. Herein, we briefly, review these reports and expand this body of literature with the inclusion of new data recently obtained in our laboratory. We confirm the blunting effects of EtOH on the production of interleukin-2 and mitogen proliferative response following T-cell mitogen stimulation, and on the expression of membrane markers of activation. We show that EtOH significantly alters the expression of the CD4 cell-associated marker of activation, CD26. We report the effect of EtOH on the expression of the homing receptor CD62L by CD4⁺ cells, and on their ability to adhere by a CD18-mediated process to a defined cellular substratum. Furthermore, we demonstrate the effects of EtOH and EtOH and 0-endor-phin pretreatment on the activation of CD4⁺ lymphocytes endowed with the homing receptor CD62L.     

人工全膝关节置换术中联合股骨外髁滑移截骨术矫正股骨外弓畸形的疗效分析

目的探讨人工全膝关节置c62;术（total knee arthroplasty，TKA）中采用股骨外髁滑移�622a;骨术（lateral condyle sliding osteotomy，LCSO）矫正股骨外弓畸_62;的疗效。方法回顾分析2018年7月—2020年7月TKA中采用LCSO治疗的17例伴股骨外弓畸_62;的骨关节炎患者临床资料。男3例，女14例；年龄58～68岁，平均63.2岁。股骨外弓畸_62;病因：股骨发育畸_62;12例，股骨骨�6298;畸_62;愈合5例。膝关节骨关节炎Kellgren-Lawrence分级：!62;级4例，Ⅳ级13例。术前生理外翻角为9.5°～12.5°，平均10.94°。病程3～25年，平均15.1年。术前及末次随访时测量股骨远端机械外侧角（mechanical lateral distal femur angle，mLDFA）、髋-膝-踝角（hip-knee-ankle angle，HKA）、机械轴偏向（mechanical axis deviation，MAD），评估关节外畸_62;在关节内矫正及下肢机械力线`62;复情况；采用膝关节学会评分系统（KSS）膝评分和功能评分、疼痛视觉模�62df;评分（VAS）、膝关节活动度（range of motion，ROM）评估疗效；行膝内、外翻应力试验，X线片复查�622a;骨片愈合情况，评估关节稳定性及LCSO的安全性。结果术后患者切口均Ⅰ期愈合，无切口感染、下肢深静脉血栓_62;�6210;等术后早期并发症发生。17例患者均获随访，随访时间12～36个月，平均23.9个月。�622a;骨片均达骨性愈合，愈合时间2～5个月，平均3.1个月。术后膝内、外翻应力试验均为阴性，未发生外侧副韧带松弛、断裂，膝关节不稳，假体松动、翻修、感染等情况。末次随访时mLDFA、HKA、MAD及膝关节ROM、VAS评分、KSS膝评分和功能评分均较术前显著改善，差异有统计学意义（P<0.05）。 结论在伴有股骨外弓畸_62;TKA中应用LCSO疗效确切且安全，关节外畸_62;在关节内矫正，一次�624b;术可同时`62;复下肢机械力线和关节平衡。     

The effects of parkin suppression on the behaviour, amyloid processing, and cell survival in APP mutant transgenic mice

Parkin suppression induces accumulation of β-amyloid in mutant tau mice. We studied the effect of parkin suppression on behaviour and brain pathology in APP_swe mutant mice. We produced double mutant mice with human mutated APP_swe + partial (hemizygote) or total (homozygote) deletion of Park-2 gene. We studied the development, behaviour, brain histology, and biochemistry of 12- and 16-month-old animals in 6 groups of mice, with identical genetic background: wild-type (WT), APP_swe overexpressing (APP), hemizygote and homozygote deletion of Park-2 (PK^+/− and PK^−/−, respectively), and double mutants (APP/PK^+/− and APP/PK^−/−).APP mice have reduced weight gain, decreased motor activity, and reduced number of entrances and of arm alternation in the Y-maze, abnormalities which were partially or completely normalized in APP/PK^+/− and APP/PK^−/− mice. The double mutants had similar number of mutant human APP transgene copies than the APP and levels of 40 and 80 kDa proteins; but both of them, APP/PK^+/− and APP/PK^−/− mice, had less plaques in cortex and hippocampus than the APP mice. APP mutant mice had increased apoptosis, proapoptotic Bax/Bcl2 ratios, and gliosis, but these death-promoting factors were normalized in APP/PK^+/− and APP/PK^−/− mice. APP mutant mice had an increased number of tau immunoreactive neuritic plaques in the cerebral cortex as well as increased levels of total and phosphorylated tau protein, and these changes were partially normalized in APP/PK^+/− heterozygotic and homozygotic APP/PK^−/− mice. Compensatory protein-degrading systems such as HSP70, CHIP, and macroautophagy were increased in APP/PK^+/− and APP/PK^−/−. Furthermore, the chymotrypsin- and trypsin-like proteasome activities, decreased in APP mice in comparison with WT, were normalized in the APP/PK^−/− mice.We proposed that partial and total suppression of parkin triggers compensatory mechanisms, such as chaperone overexpression and increased autophagy, which improved the behavioural and cellular phenotype of APP_swe mice.     

多功能蛋白p62调节细胞自噬及相关疾病的研究进展

Sequestosome 1 （p62/SQSTM1）是一种由应激诱导产生的细胞内蛋白并作用于选择性自噬的多功能蛋白.p62包含多种蛋白作用域,可结合聚泛素化蛋白并将其进一步降解,在信号转导过程中发挥重要作用.研究表明,p62参与多种疾病的病理过程,如神经退行性疾病、糖尿病、肥胖甚至是癌症.因而从p62的结构和功能这两方面阐述其在相关疾病中的作用很有必要.     

小剂量肝素对脓毒症患者血小板表面膜糖蛋白和血栓烷B2表达的影响

目的探讨小剂量肝素治疗脓毒症患者血小板表面膜糖蛋白（clusterofdifferentiation62p,CD62p）、血栓烷B2（thromboxaneB。,TXB2）水平变化及临床意义。方法44例脓毒症患者随机分为抗凝组23例（常规治疗基础上应用肝素5u／（kg·h）持续静脉泵入,疗程1周）与未抗凝组21例（采用常规治疗）,体检健康者23例为对照组;采用ELISA法检测抗凝组与未抗凝组人院第1、4、7、10天血清TXB。及CD62p水平,检测2组凝血指标水平变化,检测对照组血清TXB。及CD62p水平;观察抗凝组与未抗凝组APACHEⅡ评分及28d病死率。结果治疗前抗凝组与未抗凝组血清TXB2及CD62p水平均明显高于对照组（P〈0．05）;抗凝组人院第7、10天血清CD62p与TXB2水平均低于未抗凝组及人院第1天（P均GO．01）,入院第10天APACHEⅡ评分低于未抗凝组及人院第1天（P均G0．01）;抗凝组28d病死率（21．73％）与未抗凝组（28．57％）比较差异无统计学意义（P〉0．05）;脓毒症患者人院时血清CD62p及TXB2表达水平与APACHEⅡ评分呈正相关（r=0．804,P=0．000;r=0．742,P=0．000）。结论小剂量肝素持续泵人治疗脓毒症可明显抑制TXB2及CD62p表达,其对预测脓毒症严重程度有一定意义。