摘要：脊柱微创外科协作机器人(Cobot)是为克服外科医师手术时定位精度难以保证,长时间手术容易疲劳等问题,针对脊柱手术中的椎弓根螺钉固定术设计出的一整套“机器人”智能系统[1]。因其主要职能为辅助脊柱外科医师完成手术,故称之为协作机器人。目前,脊柱微创手术中使用的协作机器人主要是通过影像系统(C形臂X线机、CT或MRI)进行术前规划和实时导航,并使用多自由度机械臂进行操作,主要用于椎弓根螺钉辅助置入,例如Mazor系列机器人、天玑骨科手术机器人。此外,术者远程操纵、人机交互的机器人(如达芬奇手术机器人系统)也在临床试验中,术者可通过机械臂操纵手术工具和控制摄像设备,完成脊柱外科中精细的手术动作。本文就目前脊柱微创外科协作机器人技术的临床应用现状及最新进展进行文献总结。

摘要：阐述了高校实验室建设的必要性和重要性,结合北京大学医学部实验室建设的实践与经验,对高校实验室建设在规划、设计、管理等方面提出建议,并从药学专业实验室布局、类型及功能的角度,探讨了该类实验室的建设。

摘要：目的探讨多模态影像三维重建联合神经导航在功能区胶质瘤手术中的作用。方法回顾性分析2018年4月至2021年3月于北京大学第三医院神经外科行手术治疗的30例累及功能区胶质瘤患者的临床资料。术前将患者的头颅增强MRI、弥散张量成像CT血管成像(或磁共振血管成像)等数据进行影像融合以重建神经纤维束、肿瘤、血管、颅骨等结构,从而设计最佳手术路径,并应用于神经导航指导肿瘤的切除。术后72h复查头颅MRI以判断肿瘤切除程度。术后1周、1个月及3个月分别采用波土顿诊断性失语症检查量表评估语言功能,采用简化Fugl-Meyer运动功能量表评估运动功能。结果通过三维影像重建结果,所有患者均可清晰显示肿瘤与周围的重要神经纤维束、动脉、静脉等的解剖关系,明确神经纤维束的位移和破坏、供血动脉及引流静脉情况。30例患者中,肿瘤累及运动区21例,累及语言区25例。肿瘤全切除28例(93.3%),次全切除2例(6.7%)。21例术前存在神经功能缺损症状的患者中,末次随访时,20例术后神经功能改善,1例神经功能同术前;9例术前无神经功能缺损症状的患者术后出现一过性神经功能缺失相关症状,1周后症状消失。结论应用多模态影像三维重建肿瘤及周围神经纤维束、血管等重要结构,从而设计手术入路并应用于术中导航以指导手术,有助于对脑功能区的保护并提高手术疗效。

摘要：Recombinant tissue plasminogen activator （rPA） has been used as a thrombolytic agent. However, considerable improvements have been done to prolong its plasma half-life （tl/2） and reduce its side effects, such as intracranial hemorrhage. Based on these improvements, a mutant ofrPA, mrPA, was designed by mutating its PAI-1 binding site to extend its tl/2. Furthermore, a fusion protein conjugating mrPA with NR3 was designed, which was a rAcAp5 mutant with a platelet GPIIb/IIIa-binding RGD motif, to enhance the ability of targeted-thrombus and thrombolysis. The synthesized DNA sequences coding the two proteins were amplified by PCR, cloned into pET30a to construct recombinant plasmids pET30a-mrPA and pET30a-mrPA-NR3, and transformed into E. coli BL21 （DE3）. The two proteins were expressed in inclusion bodies induced by isopropy113-D-1-thiogalactopyranoside. After purified to qualified purity using one-step Ni affinity chromatography, the denatured proteins were refolded by dialysis. Their thrombolytic effects in vitro and in vivo were evaluated. In vitro 3.5 and 7 pmol/L of mrPA significantly reduced thrombus weight; 1.75, 3.5 and 7 ~tmol/L of mrPA-NR3 also significantly reduced the thrombus weight, and mrPA-NR3 displayed stronger thrombolytic effects than mrPA at 7 lamol/L. In vivo both mrPA and mrPA-NR3 showed significantly thrombolytic effect at 60-240 ktmol/kg in thrombolytic model of inferior vena cava. Importantly, mrPA-NR3 exhibited more potent thrombolytic effect than both mrPA and rhM-tPA （positive control） at 240 ***/kg. In addition, these two novel proteins did not increase bleeding time while they exerted thrombolytic effect. In conclusion, we engineered two novel proteins and proved that fusion protein had better thrombolytic effect than non-fusion protein, and the results suggest that dual thrombolytic mechanism or thrombus-target potentiated the thrombolytic effect ofrPA and alleviated hemorrhage side reaction. This study may shed light on the developme

摘要：A new series of sulfonamide flavone derivatives are designed as non-covalent inhibitors of proteasome assisted with computer-aided drug design （CADD）. The desired compounds were synthesized successfully and the biological evaluation was subsequently accomplished. The results showed negligible improvement from our lead compound （IC50 for β5 subunit was 14.0 μM）. Thus, these flavone derivatives might be improved as potential 20S proteasome inhibitors.

摘要：目的以北京大学第一医院近11年发表的学术论文为切入点,分析其科研领域国际合作情况,为后续科研工作方案的制定提供借鉴。方法运用文献计量分析法对其国际合作现状与趋势、期刊分布、偏好、学科分布与参与度进行分析。结果研究发现近年来国际合作效果较好,但国际合作率基本持平,合作水平有待继续提升。不同学科的国际合作水平存在一定差异,强势学科国际合作程度较高。研究主要集中于临床医学领域,基础研究及其他交叉学科研究有待加强。结论在后续的工作中,应当进一步完善国际合作顶层设计,提升基础研究及交叉学科研究的国际合作水平,同时推动学科建设的发展。

摘要：设计合成了一系列新型的N1-(5-取代基-1,3,4-噻二唑-2-基)-N3-取代苯基-脲类化合物,并测定了它们的抗肿瘤活性.标题化合物对肿瘤转移的生物活性实验是以荷Lewis肺癌小鼠为模型的.生物活性表明部分标题化合物对肿瘤的转移和肿瘤生长具有较好的抑制作用.其结构经元素分析、红外光谱及1H NMR确证.

摘要：As important constitutes in many drugs, piperazine comprised compounds are of great interest for drug design. In this paper, two piperazine-based compounds were synthesized for the first time, with different strategies exploited. For one compound, a highly reactive intermediate of isothiocyanate was constructed to get the desired piperazinecarbothioamide. The synthesis of the other compound was completed sequentially through Friedel-Crafts acylation, coupling reaction and Michael addition. Both synthetic routes have short steps and acceptable yields, and such strategies can be applied to the synthesis of similar oioerazine-containin~ comoounds.

摘要：脑组织间液(brain interstitial fluid,ISF)流动性的定量分析与测量一直是脑微循环研究领域的难题.之前关于脑ISF引流的研究多为离体实验,并且无法提供ISF所在细胞外间隙(brain extracellular space,ECS)的空间结构信息.本研究应用钆-二乙三胺五乙酸(gadolinium-diethylene triaminepentaacetic acid,Gd-DTPA)作为示踪剂,利用磁共振成像(magnetic resonance imaging,MRI)实现了同时对脑ISF和ECS的在体成像和定量测量.将微量Gd-DTPA(2μL,10mmol/L)缓慢导入雄性成年SD大鼠尾状核(n=8)后,进行脑MRI动态扫描(1,2,3,4,6,9,12h).结果显示,脑ISF由尾状核向额顶区皮层方向分布,3h扩散至脑皮层区后进入蛛网膜下腔.根据数学经典扩散模型计算得到,示踪分子的扩散和清除速率常数分别为(3.38±1.07)×10?4mm2/s和(7.60±4.18)×10?5/s,证实ISF在ECS内的分布引流是扩散和总体流动二者共同作用的结果.应用本研究提供的新方法可以实现对脑ECS和ISF在体定量测量和可视化分析研究,将为经脑间质给药治疗脑病提供理论基础,为给药方案设计提供重要依据.

摘要：目的 测定不同胃疾病分离的幽门螺杆菌（Hp）临床菌株中硫氧还蛋白（Trx）1、2基因序列,并确定其氨基酸序列,探讨其与相关疾病的关系.方法 通过胃镜获取慢性胃炎、消化性溃疡、胃癌3种疾病共25例患者的胃黏膜组织,从中分离培养Hp菌株,提取基因组DNA.根据GenBank基因组中Hp基因序列设计Trx1、Trx2引物,应用聚合酶链反应（PCR）进行扩增,对扩增产物进行序列测定及生物信息学分析,并与国际标准菌株比对.结果 应用PCR的方法成功扩增出Trx1全基因序列及Trx2基因前295核苷酸.应用BioEdit软件进行核苷酸和氨基酸同源性分析,不同疾病分离的Hp Trx1均含有321个核苷酸,总突变位点率13.4%（43/321）;编码106个氨基酸,含有一个Cys-Gly-Pro-Cys氧化还原活性位点,25例不同胃疾病Hp TRX1的氨基酸同源性高达97.2%（103/106）.Trx2的前295个核苷酸,总突变位点率18.6%（55/295）;编码的氨基酸无Cys-Gly-Pro-Cys,含有一个CXXC区域,氨基酸同源性为84.7%（83/98）.结论 Hp临床分离菌株的Trx两个亚型核苷酸序列均有不同程度的位点突变,但氨基酸的序列同源性较高,均为无效突变.不同疾病分离的Hp Trx1均含有一个Cys-Gly-Pro-Cys氧化还原活性位点,TRX2仅含有一个CXXC区域.研究结果为进一步探讨Hp Trx的生物学功能及其致病机制提供了可靠依据.