Enhanced Anti-Leukemic Effects through Induction of Immunomodulating Microenvironment by Blocking CXCR4 and PD-L1 in an AML Mouse Model

Previously, we found that dual therapy by the CXCR4 inhibitor Plerixafor and cytosine arabinoside (Ara-C) effectively eradicated leukemia cells and concurrently activated immune cells in acute myeloid leukemia (AML). To reveal the significance of programmed death-ligand1 (PD-L1) in AML and as a strategic approach, we investigated the anti-leukemic effect of a triple combinational therapy by utilizing Plerixafor and anti-PD-L1 in combination with chemotherapy in an AML mouse model. We examined leukemic myeloid blast cells in multiple organs after the successive treatment with Ara-C, Plerixafor, and anti-PD-L1. The results showed that noticeable benefits of triple combinational therapy for eradication of myeloid blast cells in vivo with prolonged survival rates. The frequencies of regulatory T cells (Tregs), monocytic-myeloid-derived suppressor cells (M-MDSCs), and granulocytic-myeloid-derived suppressor cells (G-MDSCs), in the peripheral blood of leukemic mice were consistently decreased, even when mice were sacrificed alive at D + 26 after completion of the triple combinational therapy, compared to the other subgroups. These findings imply that the modulation by the triple combinational therapy may lead to more efficient leukemic myeloid blast cell ablation through the suppression of Tregs or M-MDSCs and G-MDSCs in AML. Although Plerixafor and PD-L1 antagonist do not have a direct anti-leukemic role, our results provide some clues and guidelines to develop clinically therapeutic strategies for chemotherapy-resistant patients by the modulation of leukemic microenvironments.     

Spatial and seasonal bacterioplankton community dynamics in the main channel of the Middle Route of South-to-North Water Diversion Project

In this study, the spatial and seasonal bacterioplankton community dynamics were investigated in the main channel of the Middle Route of the South-to-North Water Diversion Project (MRP) using Illumina HiSeq sequencing. Water samples were collected in spring and summer from south to north at eight water quality monitoring stations, respectively. The results showed that seasonal changes had a more pronounced effect on the bacterioplankton community compositions (BCCs) than spatial variation. The diversity analysis results indicated that samples of summer have more operational taxonomic units (OTUs), higher richness and diversity than those in spring. The main phyla, Proteobacteria, Actinobacteria, Bacteroidetes, Cyanobacteria and Chloroflexi, displayed significant differences (P < 0.05) between spring and summer in the main channel. The Redundancy analysis (RDA) targeting all samples indicated that specific conductivity (SPC), dissolved oxygen (DO), pH and temperature (T) might be key factors in driving BCCs, while trophic status showed no significant correlation (P > 0.05). The present study provides important insights into the potential ecological roles of specific taxa in the new artificial ecosystem and it offers reference for studies on ecosystem succession of other giant interbasin water diversion project in the world.     

手舟骨腰部骨折3种内固定方式的有限元分析

目的　通过建立手舟骨腰部骨折三维模型来比较3种不同内固定方式的生物力学差异,为临床内固定方式的选择提供依据。 方法　选取健康志愿者的腕关节CT数据,应用软件建立舟骨腰部骨折的3种内固定方式模型：克氏针固定组、Herbert螺钉固定组、钉脚固定器组。分别在中立握拳位和腕背伸桡偏位施加载荷,并分析舟骨变形量、内固定器械的应力。 结果　在3种内固定装置下舟骨的变形量,克氏针最大,钉脚固定器最小。在两种工况下,舟骨变形量和固定装置的最大应力值不等,但趋势相同,均为钉脚固定器的舟骨变形量最小、所受的最大应力最小。钉脚固定器存在偏心效应,当载荷达到临界值时,易使舟骨愈合面出现开裂或不对称偏心现象。 结论　克氏针固定效果最差,钉脚固定器的固定效果最佳,钉脚固定器术后应适当限制手部负重。     

腹壁下动脉缺如伴腹股沟斜疝1例

<正>笔者在局解教学过程中发现一具标本存在右侧腹壁下动脉缺如的情况。为积累资料及为临床提供参考,现报道如下:该标本系老年男性,体质良好。左侧腹壁诸层结构正常,腹壁下动脉完好。右侧腹壁层次尚可,右侧腹直肌下部肌质较薄,内侧越过白线与左侧腹直肌融合,但右侧腹壁下动静脉缺如(图1A),也未见异位腹壁下动脉分支。此外可见右侧腹     

微创手术机器人机械臂结构设计与工作空间分析

目的现有双平行四边形机构设计的机械臂需要串联一个伸缩自由度机构,导致机械臂体积增大,运动灵活性降低,持镜臂与持器械臂发生干涉。针对这一问题,提出一种新型机械臂结构,增强运动灵活性、减小机械臂的体积。方法采用5连杆机构、滑块与滑轨的低副机构和丝传动机构设计机械臂,实现末端执行器的伸缩运动,建立机械臂的运动学模型,以MATLAB为仿真工具验证零位关节角D-H参数的正确性,求解出机械臂的运动方程;同时运用蒙特卡洛算法,得到末端执行器的三维工作空间范围,并对3条机械臂作术前动物实验规划;最后,在猪体内进行胆囊切除等操作,验证机械臂的双5连杆2自由度设计的合理性和可操作性。结果蒙特卡洛算法在MATLAB环境下得到的工作空间范围为:-650.4 mmx649 mm,163.8 mmy1 202 mm,-254.6 mmz829.8 mm,并成功完成16例猪的胆囊切除实验,平均操作时间为51 min。结论新型设计的双5连杆2自由度机械臂在猪体内成功完成胆囊切除等操作,且猪术后无其他不良症状,机械臂之间的运动无干涉,充分验证了所提出的微创手术机器人机械臂设计方案的可行性。     

Functional characterization of CEP250 variant identified in nonsyndromic retinitis pigmentosa

Retinitis pigmentosa (RP) is the most common manifestation of inherited retinal diseases with high degree of genetic, allelic, and phenotypic heterogeneity. CEP250 encodes the C‐Nap1 protein and has been associated with various retinal phenotypes. Here, we report the identification of a mutation (c.562C>T, p.R188*) in the CEP250 in a consanguineous family with nonsyndromic RP. To gain insights into the molecular pathomechanism underlying CEP250 defects and the functional relevance of CEP250 variants in humans, we conducted a functional characterization of CEP250 variant using a novel Cep250 knockin mouse line. Remarkably, the disruption of Cep250 resulted in severe impairment of retinal function and significant retinal morphological alterations. The homozygous knockin mice showed significantly reduced retinal thickness and ERG responses. This study not only broadens the spectrum of phenotypes associated with CEP250 mutations, but also, for the first time, elucidates the function of CEP250 in photoreceptors using a newly established animal model.     

Functional Mixed Effects Model for the Analysis of Dose-Titration Studies

Functional data analysis, which analyzes data that can be represented by curves or images, has many potential applications in clinical trials. Motivated by a real example, this study constructs a functional mixed effects model for analyzing a clinical outcome that is observed continuously over a long period of time. A penalized spline (P-spline)-based method is applied to obtain the estimators of the mean function and the time-varying coefficients. Simulation studies are conducted to investigate the consistency, efficiency, and robustness of the method. To illustrate the use of the method, a real data analysis is performed and produces interpretable results.     

赤石脂和禹余粮作为灶心土替代品的分析

目的:通过比较灶心土、赤石脂和禹余粮的热解特性及红外光谱相似度来探讨赤石脂、禹余粮替代灶心土的可行性。方法:热解特性研究采用热重差热综合热分析仪,取试样量(30±5)mg置于坩锅中,以10℃·min~(-1)的升温速率、流量60 m L·min~(-1)的恒定流速通入模拟空气[N_2-O_2(4∶1)],从室温升至900℃。红外光谱试验采用溴化钾压片法,光谱分辨率4 cm~(-1),测量范围4 000~500 cm-1,扫描信号累加32次,所得数据经Omnic软件进行自动基线校正、平滑及纵坐标归一化。数据处理及图表绘制采用Origin 8.0软件和Omnic软件完成。结果:比较热解特性发现灶心土、赤石脂、禹余粮的热解特性均在400~600℃处出现一段失重台阶;但整体而言,赤石脂与禹余粮热解特性没有体现出灶心土热解特性的复杂性;通过红外光谱相似度数值得出,以灶心土作为对照,赤石脂与灶心土相似度数值较偏低,禹余粮与与灶心土相似度数值处于中等水平。结论:就热解特性及红外光谱相似度而言,禹余粮与灶心土相似性较好,可能较赤石脂更适用作灶心土的替代品,为相关中药炮制辅料的研究提供参考。     

大黄、地榆、牡丹皮炒炭过程中热解反应机制的分析

目的:推断并验证大黄、地榆、牡丹皮3味中药炒炭的热解反应机制,进一步完善这3味中药炒炭研究的理论。方法:采用模式函数法中的单个扫描速率的不定温法(Coats-Redfern模型与Achar模型)推断大黄、地榆、牡丹皮3味中药炒炭过程中热解反应的机理函数,通过比较转化率(α)理论值、实验值与1/T的热分析曲线对机理函数进行验证。结果:积分形式表达式能更较好地描述大黄、地榆、牡丹皮3味中药炒炭热解的反应机制,三者的炒炭热解机理函数分别为9号机理函数积分形式g(α)=[(1-α)-1/3-1]2,2号机理函数积分形式g(α)=α+(1-α)ln(1-α),9号机理函数积分形式g(α)=[(1-α)-1/3-1]2。结论:3味中药炒炭的热解反应机制均属于反应扩散,转化率理论值与实验值存在一定的差异,运用热分析动力学方法只是尽可能地模拟这3味中药的炒炭热解反应过程。     

川芪眼用微乳原位凝胶的流变学及释放动力学分析

目的:研究考察川芪眼用微乳原位凝胶的流变学及释放动力学行为,为该制剂的后续研究与开发提供参考。方法:使用MCR 102型流变仪考察川芪眼用微乳原位凝胶的流体性质及线性粘弹区域。体外释放度采用改良Franz扩散池法,以半透膜为释放膜,川芎嗪、藁本内酯为指标成分,取样时间点分别为0.5,1,2,4,6,8 h。结果:川芪眼用微乳原位凝胶是一种假塑性流体并存在线性粘弹区域。以剪切力为指标,确定的线性粘弹区域为0~302.74 Pa,以形变为指标得到的线性粘弹区域范围为0~7.45%。在临界点时,其储能模量(G')等于损耗模量(G″),均为2 976.60 Pa;临界剪切力为302.74 Pa;临界形变7.45%。8 h内6份样品中川芎嗪的平均累积释放量33.71μg,平均累积释放率90.08%,释放动力学遵循Higuchi方程。8 h内6份样品中藁本内酯平均累积释放量为68.46μg,平均累积释放率为84.32%,其释放动力学遵循零级动力学方程。结论:川芪眼用微乳原位凝胶具有较好的粘弹性,并在一定范围内可以发生可逆形变。川芎嗪释放动力学是川芎嗪的理化性质与基质骨架共同作用的结果,藁本内酯的释放动力学主要受其理化性质的影响。