C5a/C5a R pathway is essential for up-regulating Sph K1 expression through p38-MAPK activation in acute liver failure

AIM To investigate the role of the complement 5a(C5a)/C5 a receptor(C5a R) pathway in the pathogenesis of acute liver failure(ALF) in a mouse model.METHODS BALB/c mice were randomly assigned to different groups, and intraperitoneal injections of lipopolysaccharide(LPS)/D-galactosamine(D-Gal N)(600 mg/kg and 10 μg/kg) were used to induce ALF. The KaplanMeier method was used for survival analysis. Serum alanine aminotransferase(ALT) levels, at different time points within a 1-wk period, were detected with a biochemistry analyzer. Pathological examination of liver tissue was performed 36 h after ALF induction. Serum complement 5(C5), C5 a, tumor necrosis factor-α(TNF-α), interleukin(IL)-1β, IL-6, high-mobility group protein B1(HMGB1) and sphingosine-1-phosphatelevels were detected by enzyme-linked immunosorbant assay. Hepatic morphological changes at 36 h after ALF induction were assessed by hematoxylin and eosin staining. Expression of C5 a R, sphingosine kinase 1(Sph K1), p38-MAPK and p-p38-MAPK in liver tissue, peripheral blood mononuclear cells(PBMCs) and peritoneal exudative macrophages(PEMs) of mice or RAW 264.7 cells was analyzed by western blotting. C5 a R m RNA levels were detected by quantitative real-time PCR.RESULTS Activation of C5 and up-regulation of C5 a R were observed in liver tissue and PBMCs of mice with ALF. Blockade of C5 a R with a C5 a R antagonist(C5a Ra C5 a Ra) significantly reduced the levels of serum ALT, inflammatory cytokines(TNF-α, IL-1β and IL-6) and HMGB1, as well as the liver tissue damage, but increased the survival rates(P < 0.01 for all). Blockade of C5 a R decreased Sph K1 expression in both liver tissue and PBMCs significantly at 0.5 h after ALF induction. C5 a Ra pretreatment significantly downregulated the phosphorylation of p38-MAPK in liver tissues of ALF mice and C5 a stimulated PEMs or RAW 264.7 cells. Moreover, inhibition of p38-MAPK activity with SB203580 reduced Sph K1 protein production significantly in PEMs after C5 a stimulation.CONCLUSION The C5a/C5 a R pathway is essential for up-regulating Sph K1 expression through p38 MAPK activation in ALF in mice, which provides a potential immunotherapeutic strategy for ALF in patients.

IP3R2及RYR2介导Ca^(2+)信号在急性一氧化碳中毒迟发性脑病小鼠模型中的表达

背景:研究发现星形胶质细胞中Ca^(2+)的表达与认知功能密切相关,目前由1,4,5-三磷酸肌醇受体(Inositol 1,4,5-trisphosphate receptors,IP3Rs)2、兰尼碱受体(ryanodine receptors,RYRs)2受体及其调控的Ca^(2+)信号通路已经成为认知障碍相关疾病研究的热点。目的:研究急性一氧化碳中毒迟发性脑病动物模型中,海马组织内星形胶质细胞和IP3R2、RYR2介导的Ca^(2+)信号的表达情况,探索急性一氧化碳中毒迟发性脑病可能的发病机制。方法:Morris水迷宫实验筛选认知功能合格的C57BL小鼠随机分为对照组、实验组,实验组小鼠采用静态吸入一氧化碳建立急性一氧化碳中毒迟发性脑病模型,对照组小鼠吸入等量空气。造模后第21天,利用Morris水迷宫、苏木精-伊红染色、Western blot、免疫荧光双标法、Ca^(2+)荧光探针检测中毒小鼠行为学及神经元改变、星形胶质细胞特异性标记物胶质纤维酸性蛋白及IP3R2、RYR2受体、星形胶质细胞内Ca^(2+)浓度变化。结果与结论:①Morris水迷宫实验发现与对照组相比,实验组小鼠逃避潜伏期明显延长(P<0.05);②苏木精-伊红染色表明实验组小鼠海马锥体细胞数减少、细胞结构紊乱、细胞核碎裂伴溶解;③免疫荧光检测表明海马区IP3R2、RYR2分别和胶质纤维酸性蛋白存在共表达,且实验组海马区IP3R2、RYR2和胶质纤维酸性蛋白表达均上调(P<0.05);④Western blot检测显示实验组海马区IP3R2、RYR2及胶质纤维酸性蛋白的蛋白表达均增多(P<0.05);⑤Ca^(2+)荧光探针法检测表明实验组小鼠海马区星形胶质细胞内Ca^(2+)浓度明显升高(P<0.05);⑥结果说明,星形胶质细胞可能通过介导IP3R2、RYR2受体影响Ca^(2+)信号,进而使一氧化碳中毒的小鼠认知功能受损,最终导致急性一氧化碳中毒迟发性脑病发生。

Prolonged intermittent theta burst stimulation restores the balance between A_(2A)R-and A_(1)R-mediated adenosine signaling in the 6-hydroxidopamine model of Parkinson's disease

An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease progression,demonstrating the need for novel approaches in PD.Repetitive transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's disease.However,the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain unknown.The purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated signaling.Animals with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod test.Immunoblot,quantitative reverse transcription polymerase chain reaction,immunohistochemistry,and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate putamen.Prolonged intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals.A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate putamen.Treatment with intermittent theta burst stimulation began 7 days after the lesion,coinciding with the onset of motor symptoms.After treatment with prolonged intermittent theta burst stimulation,complete motor recovery was observed.This improvement was accompanied by downregulation of the e N/CD73-A_(2A)R pathway and a return to physiological levels of A_(1)R-adenosine deaminase 1 after 3 weeks of intermittent theta burst stimulation.Our results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A_(1)R and elevated the expression of A_(2A)R.Intermittent theta burst stimulation reversed these effects by restoring the abundances of A_(1)R and A_(2A)R to control levels.The shift in ARs expression likely restored the balance between dopamine-adenosine signaling,ultimately leading to the recovery of motor control.

UPLC测定丹七片中三七皂苷R_1、人参皂苷Rg_1和人参皂苷Rb_1的含量

目的建立超高效液相色谱法（ultra performance liquid chromatography,UPLC）分离测定丹七片中三七皂苷R1、人参皂苷Rg1、人参皂苷Rb1含量。方法采用ACQUITY UPLC HSS T3（2.1 mm×50 mm,1.8μm）色谱柱,柱温30℃,以乙腈（A）-水（B）为流动相,梯度洗脱,流速0.3 m L/min,检测波长203 nm,进样体积2μL。结果三七皂苷R1、人参皂苷Rg1、人参皂苷Rb1分别在0.0300~0.3000,0.1201~1.2009,0.1200~1.1997μg范围内线性关系良好,方法重复性及回收率均符合要求,平均加样回收率（n=6）分别为100.43%、100.65%、98.74%,RSD值分别为1.51%、1.30%、1.03%。按测定的方法测定市售2种丹七片的含量相近。结论该方法简便、高效、准确、重复性好,分析速度提高近8倍,可以用于测定丹七片中三七皂苷R1、人参皂苷Rg1、人参皂苷Rb1的含量。

多波长UPLC法同时测定冠心丹参胶囊中三七皂苷R_1等5种有效成分的含量

目的利用多波长超高效液相色谱法,建立冠心丹参胶囊中三七皂苷R1、人参皂苷Rg1、人参皂苷Rb1、丹酚酸B和丹参酮ⅡA5种有效成分的含量测定方法。方法采用ACQUITY UPLC HSS T3（100 mm×2.1 mm,1.8μm）色谱柱,柱温为30℃,以乙腈和体积分数为0.1%磷酸溶液为流动相,采用梯度洗脱,流速为0.4 mL·min^-1,检测波长为203 nm（三七皂苷R1、人参皂苷Rg1、人参皂苷Rb1）、286 nm（丹酚酸B）和270 nm（检测丹参酮ⅡA）。结果三七皂苷R1、人参皂苷Rg1、人参皂苷Rb1、丹酚酸B和丹参酮ⅡA分别在质量浓度10-200 mg·L^-1（r=0.999 7）、20-800 mg·L^-1（r=0.999 3）、20-800 mg·L^-1（r=1.000 0）、20-800 mg·L^-1（r=1.000 0）和1-50 mg·L^-1（r=0.999 5）内与峰面积呈良好线性关系;加样回收率（n=6）：三七皂苷R1为95.0%（RSD=1.2%）、人参皂苷Rg1为105.4%（RSD=1.9%）、人参皂苷Rb1为98.8%（RSD=0.9%）、丹酚酸B为97.4%（RSD=2.6%）、丹参酮ⅡA为104.9%（RSD=4.8%）。结论本方法简便可行,为冠心丹参胶囊质量控制提供了一种可靠的检测方法。

Kinematics and dynamics analysis of a 3-7R parallel decoupling mechanism

One kind of movable-pair analysis method is adopted to analyze the configuration of a 3-7R （revolute-pair） parallel decoupling mechanism, and the mechanism＇s characteristics are summarized. The mechanism has three orthogonal distributional branch-chains, and all movable pairs are rotational joints. The movable platform of the mechanism has x, y, z translational decoupling directions. Furthermore, in order to verify the mechanism＇s decoupling characteristics, the mechanism＇s kinematics analysis is solved, and the mechanism＇s direct/inverse kinematics model, input/output velocities and accelerations are deduced, which confirm its decoupling movement characteristics. Finally, one kind of mechanism link decomposed-integrated approach is adopted, and the mechanism＇s dynamics model is completed with the Lagrange method, which also proves its decoupling force characteristics. All of these works provide significant theory for the further study of the mechanism＇s control strategy, design, path planning etc.

uPA和LN-R在良、恶性甲状腺病变中的表达及临床病理意义

目的研究uPA、LN-R在良、恶性甲状腺病变中的表达特点,并探讨其与甲状腺癌临床预后指数的关系。方法应用组织芯片和免疫组化检测28例结节性甲状腺肿、17例甲状腺滤泡性腺瘤、55例甲状腺乳头状癌、7例未分化癌、5例髓样癌、5例滤泡性癌、2例低分化岛状癌及1例鳞状细胞癌组织中uPA、LN-R的表达。结果uPA、LN-R在甲状腺癌中表达阳性率分别为80%和57.33%;在甲状腺良性病变中表达阳性率分别为6.67%和0。uPA、LN-R在欧洲癌症治疗研究组织(EORTC)预后指数不良组表达阳性率分别为91.49%和70.21%;在EORTC预后指数良好组表达阳性率分别为60.71%和35.71%。在甲状腺良、恶性病变中uPA和LN-R蛋白的表达呈显著正相关(χ2=26.194,r=0.467,P<0.01)。结论uPA、LN-R可以作为良、恶性甲状腺病变鉴别诊断的指标,也是判断甲状腺癌患者预后的指标。

Segmental Duplications Are Common in Rice Genome

Segmental duplications on rice (Oryza sativa L.) chromosomes 8, 9, 11, and 12 were studied by examining the distributions of sequences resolved by 13 probes detecting multiple copies of DNA sequences. Four of the hybridization bands detected by a repetitive sequence probe, rTRS, were mapped to the ends of all the four chromosomes. Two or three of the bands detected by each of the other 12 probes were also mapped to different chromosomes. The bands detected by the same probe usually occurred in similar locations of different chromosomes. Loci detected by different DNA probes were often similarly arranged on different chromosomes. Chromosomes 8 and 9 showed colinearity of marker loci arrangement indicating a possible common origin. A segment on chromosome 9 was also very similar to the previously reported duplicated fragments on the ends of chromosomes 11 and 12 which were also detected in this study, indicating a likely common origin. Moreover, the various degrees of distributional similarity of the segments suggest a complex relationship among the chromosomes in the evolution of the rice genome. These results support the proposition that chromosome duplication and diversification may be a mechanism for the origin and evolution of the chromosomes in the rice genome.

2-UPS/(S+SPR)R并联机构伴随运动与正反解分析

目的分析含有闭环单元的三自由度2-UPS/(S+SPR)R并联机构是否具有伴随运动,并对该机构的位姿正逆解进行分析。方法利用欧拉变化得到旋转矩阵,结合机构的结构特性建立约束方程,分析机构是否具有伴随运动和机构的位姿逆解。利用粒子群(PSO)算法分析机构的位姿正解。结果该机构不具备z轴方向的转动伴随运动,建立了位姿逆解方程;通过PSO算法在输入驱动参数的情况下,可以精确地得到动平台的位姿。结论机构不存在伴随运动,通过PSO优化算法得到了位姿正解精确的数值解,为分析机构的工作空间提供了良好的基础。

UPLC法测定九味肝泰胶囊中人参皂苷Rg_1及三七皂苷R_1的含量

目的建立九味肝泰胶囊中人参皂苷Rg1及三七皂苷R1的含量测定方法，弥补该品种质量标准的不完善之处。方法采用ACQUITYBEHC18（2．1mm×50mm，1．7μm）色谱柱；流动相为乙腈一水，梯度洗脱；流速为0．4ml／min；检测波长为203nm；柱温为35℃；进样体积为μl。结果人参皂苷R勘及三七皂苷R。分别在0．10-1．50mg／ml，0．04～0．60mg／ml浓度范围内线性良好，平均回收率分别为99．4％、101．8％，RSD分别为0．5％、1．3％。结论该法方便、快速、准确，适用于九味肝泰胶囊中人参皂苷Rg。及三七皂苷R。的含量测定，可用于该制剂的质量控制。

基于Supermap Objects的矿区三维虚拟仿真系统设计与实现

根据三维GIS特点,提出将三维GIS技术与数字矿山信息相结合的思想,阐述了基于Su-permap Objects的三维矿区仿真系统的构建流程,并以陕西冯家塔矿区三维虚拟仿真系统为例,实现了三维显示与漫游、三维地形量测、三维查询等系统主要功能。结果表明基于Supermap Objects的三维虚拟仿真系统可快速准确地实现矿区三维展示和管理,为数字矿山的建设增添新内容。

UPLC测定化瘀止痛片人参皂苷Rg1和三七皂苷R1含量实验报告

目的探讨超高效液相色谱(UPLC)测定化瘀止痛片中人参皂苷Rg1和三七皂苷R1含量。方法采用EndeavorsilTM C18(50mm×2.1mm,1.8μm)柱,流动相为乙腈-水(24:76),流速为0.4mL.min-1,柱温为室温,检测波长为203nm,进样量2μl。结果化瘀止痛片中人参皂苷Rg1和三七皂苷R1分别在1.646-82.3μg.mL-1,0.43-21.5μg.mL-1范围内与相应峰面积呈良好线性关系,平均加样回收率分别为100.07%、99.96%,RSD值分别为2.02%、2.13%(n=6)。结论与HPLC法相比,UPLC法在不影响分离效果的情况下可大大提高制剂中三七皂苷R1、人参皂苷Rg1的分析速度,改善分析效果;同时可减少溶剂的消耗。UPLC是可作为替代传统HPLC的一种更为方便、快捷、可靠的测定方法。

4R危机管理理论在结肠镜围检查期低血糖风险管理中的应用

目的探讨4R危机管理理论在结肠镜诊疗围检查期患者低血糖风险管理中应用的效果。方法采用便利抽样法,选择2022年3-12月在青岛市某三级甲等医院消化内科住院的372例行结肠镜诊疗的患者为对照组,采用结肠镜诊疗围检查期常规低血糖管理方法;选择2023年1-10月住院的372例行结肠镜诊疗的患者为观察组,实施基于4R危机管理理论的低血糖管理方案。比较2组患者结肠镜诊疗围检查期低血糖发生率、护士对结肠镜诊疗围检查期低血糖处置规范环节达标率、低血糖相关不良事件或并发症发生率的差异。结果观察组患者低血糖发生率低于对照组,护士对观察组患者低血糖处置规范环节达标率高于对照组,差异均具有统计学意义(P<0.05或P<0.001),2组患者低血糖相关不良事件或并发症发生率差异无统计学意义(P>0.05)。结论4R危机管理理论应用于结肠镜诊疗围检查期患者的低血糖管理中,能够有效降低患者低血糖发生率,提高护士对结肠镜诊疗围检查期低血糖处置正确率,值得在临床推广应用。

基于RUP的UML建模方法在人事招聘系统开发中的应用

以人事招聘系统的开发为背景,介绍在面向对象应用系统的分析与设计过程中,应用基于RUP的UML的建模技术进行系统建模的方法。在对系统进行需求分析的基础上,灵活选用UML提供的语言丰富的可视化表达元素,构建系统的用户需求模型、混合模式体系架构模型、分析设计模型和实现模型。

基于SuperMap GIS 6R软件的三维数字小区展示与查询系统的实现

以天水市华辰小区为例,研究了如何利用三维GIS技术建立高效实用的三维小区展示系统,基本实现了小区的三维漫游、空间量算以及居民属性信息的查询。本文成功地将三维建模软件和国产GIS软件SuperMap相结合,对数据进行操作。

V_(1)导联r'波振幅结合阻抗变化评价左束支区域起搏电极植入深度的研究

目的:探讨左束支区域起搏时,V_(1)导联r’波振幅结合阻抗变化判断电极植入的合适深度。方法:纳入2019年1月1日至2021年12月31日于南昌大学第二附属医院就诊的心脏结构正常、有起搏器植入指征并行左束支区域起搏的住院患者78例,收集患者基线数据、术中数据和影像学资料,以及术后3、6、9和12个月的随访情况。将起搏时V_(1)导联r’波振幅、阻抗、电极植入深度进行线性相关性及回归分析。结果:78例患者中70例(89.7%)起搏时V_(1)导联QRS波末端出现r’波,8例(10.3%)QRS波表现为r S、RS型或终末端无r’波。线性相关性分析显示,r’波振幅与电极植入深度呈正相关(r=0.424,P<0.01),与阻抗呈负相关(r=-0.256,P=0.03);电极植入深度与阻抗无明显相关性(r=-0.132,P=0.27)。回归分析显示,电极植入深度是r’波振幅的重要影响因素(回归系数=0.056,P=0.000)。结合建立的回归模型和阻抗大小显示,V_(1)导联r’波振幅在0.24~0.69 mV范围内,阻抗在648.30~828.90Ω之间,电极植入深度6~11 mm最合适,穿孔风险小,且能较大概率成功夺获左束支,起搏参数满意,起搏QRS波时限较窄。在术中、术后48 h及12个月随访期间内,患者均未出现电极穿孔、血栓栓塞、心脏填塞、感染、导线脱位等并发症。结论:左束支区域起搏是一种安全可行的起搏方式。在左束支区域起搏时,V_(1)导联r’波振幅在一定合适范围内,并结合阻抗变化可指导左束支区域起搏,有助于降低电极穿孔的风险。

4R危机管理理论在120指挥调度管理中的应用研究

“120”指挥调度作为整个院前医疗急救工作的“第一棒”,保障其安全高效运转尤其重要。通过总结淄博市医疗急救指挥中心在“120”指挥调度管理方面运用4R危机管理理论的实践,探讨如何更好地减少“120”指挥调度中危机事件的发生,进行相关制度建设,制定措施高效应对危机事件及事后恢复重建等,从而建立更安全、更高效的“120”指挥调度体系,让市民群众真正体验到高品质的院前急救服务。

MC1R基因在白羽乌骨鸡和黑羽乌骨鸡肌肉和皮肤中的表达分析

本试验旨在探明MC1R基因在白羽乌骨鸡和黑羽乌骨鸡黑色素沉积中的影响效应,为更好地开发利用地方乌骨鸡提供理论依据。以白羽乌骨鸡(丝羽乌骨鸡、竹丝鸡)和黑羽余干乌骨鸡为研究对象,屠宰拔毛后立刻测定胸部皮肤、大腿部皮肤的亮度L^(*)值,然后把测定过肤色的胸皮和大腿皮剪开,测定皮肤下面的胸肌、腿肌亮度L^(*)值,获得胸肌、腿肌、胸皮和大腿皮乌色度的变化趋势,同时比较MC1R基因在3种乌骨鸡的4种组织中的差异表达量。结果发现:2~17周龄期间,随着周龄的增加,3种乌骨鸡腿皮、胸皮、胸肌和腿肌L^(*)值均呈增加趋势;2周龄时MC1R在3种乌骨鸡胸肌、腿肌中的相对表达量较高,随后表达量呈现下降趋势,而在3种乌骨鸡胸皮和腿皮中的表达量变化趋势不同;2周龄时MC1R基因在黑羽余干乌骨鸡腿肌、胸皮和腿皮中的表达量显著大于2种白羽乌骨鸡;6周龄时MC1R基因在黑羽余干乌骨鸡腿肌和胸皮的表达量显著大于2种白羽乌骨鸡;10周龄时MC1R基因在黑羽余干乌骨鸡腿肌的表达量显著大于2种白羽乌骨鸡;10、12、17周龄时MC1R在丝羽乌骨鸡腿皮的表达量显著高于其他乌骨鸡;MC1R基因表达量与黑羽余干乌骨鸡肤色和肉色L^(*)值不相关,而与白羽乌骨鸡腿肌L^(*)值显著相关。结果提示,MC1R基因对白羽乌骨鸡和黑羽乌骨鸡黑色素沉积的影响效应不同,本研究为培育乌色度更高、不同羽色的乌骨鸡新品种提供了科学理论依据。

汽车及零部件电磁兼容测试方法基于ECE R10的变化解析

汽车电子电磁兼容性不仅是评价汽车及零部件的重要性能指标之一,也是汽车及零部件出口国外市场必要的测试之一,车企出口欧盟需要满足《关于车辆电磁兼容性能认证的统一规定》(ECE R10)要求并遵照法规要求进行电磁兼容测试。本文对比了新旧版本ECE R10对于测试方法与要求的变化,为开展汽车电子产品的电磁兼容检测和认证提供参考。

T/R双模微波功率模块技术及其应用

微波功率模块(MPM)是真空电子器件和固态电子器件组合而成的一种新型微波功率器件,具有频率高、频带宽、功率大、体积重量小等特点,它使常规行波管的应用变得更加便利和广泛。现代战争向雷达、电子战综合一体化方向发展,这就要求功放既能工作在高峰值功率、低占空比的高模工作方式,也能工作在低峰值功率、准连续波的低模工作方式,针对这一需求,结合电子系统收发共孔径的要求,提出了T/R双模MPM技术。T/R双模MPM技术的核心是T/R双模行波管,基于三端口双向T/R行波管,通过在慢波系统的衰减器附近设置一个耦合口,实现行波管的信号反向接收功能;通过T/R双模行波管设计、双模放大均衡组件、双调制栅极电源等技术实现MPM的双模双向功能。T/R双模MPM应用前景广阔,特别是在基于无人机平台的作战应用中的具有明显优势。