基于区间毕达哥拉斯犹豫模糊熵和交叉熵的ELECTRE II决策方法

针对属性权重完全未知或部分已知,属性值为区间毕达哥拉斯犹豫模糊数的多属性决策问题,提出了基于区间毕达哥拉斯犹豫模糊熵和交叉熵的ELECTRE II法。首先给出区间毕达哥拉斯犹豫模糊数的区间形式的得分函数和精度函数,定义新的距离测度。然后基于区间毕达哥拉斯犹豫模糊数的模糊因子、直觉因子和幅度因子,给出熵和交叉熵公式,并证明其性质,提出了基于熵和交叉熵确定属性权重的方法。最后提出了区间毕达哥拉斯犹豫模糊环境下的改进的ELECTRE II法,利用综合优势值对方案进行排序,并通过算例和比较分析验证了该方法的可行性和有效性。

融合NSGA-II和CSA的多目标车间调度

针对在灵活车间系统中调度作业和自动引导车(automated guide vehicle,AGV)的同时调度问题,考虑在有限多个AGV和加工机台的情况下,以最小化最大完工时间、单个AGV搬运消耗时间及所有AGV搬运总消耗时间为目标函数,设计融合NSGA-II(non-dominated sorting genetic algorithms)和克隆选择(clonal selection algorithm,CSA)的改进算法INGCSA来解决此类问题。采用工件、加工机台和AGV三部分编码;引入非支配排序和目标函数值大小排序后总得分进行种群分层,从而有效地保留优秀个体;针对克隆后的种群,对不同等级的种群采取不同的变异概率,并对染色体进行内部交换与均匀交叉混合交换的基因重组,有效地提高了种群的多样性与防止陷入局部最优。通过三组对比实验,验证了该算法在探索最优解时,具有运行时间短、稳定性高和收敛性好等优点。

基于改进NSGA-II的轨道交通接驳公交线路优化

为解决接驳公交线路规划不合理和时间安排不完善的问题,提出了基于改进NSGA-II算法的环形接驳公交线路优化方法。首先,结合双层规划理论,以乘客出行时间成本最小化、公交企业运营收益和接驳公交服务率最大化为目标函数,以接驳公交线路站点数、线路长度和发车频率作为约束条件构建上层模型,采用Logit模型构建了下层接驳客流分配模型;其次,运用Floyd算法对NSGA-II算法的初始化种群进行了优化,针对所提出的模型设计了模型求解流程;最后,以哈尔滨市轨道交通1号线医大一院轨道交通站为案例,运用笔者提出的多目标双层规划模型和算法进行求解,并与原NSGA-II算法和基于Logistic混沌映射的NSGA-II算法进行对比。研究结果表明:基于Floyd算法改进的NSGA-II算法在多目标双层规划模型求解时,收敛速度更快效果更好,求解结果可以在Pareto前沿得到多个相互非支配的最优解;不同解集对应目标函数值不同,但可以达到接驳公交网络整体效益最优,采用折衷最优解集表述求解结果。

营心宁胶囊辅助治疗对冠心病心力衰竭患者血管紧张肽II水平和心功能的影响

目的:观察营心宁胶囊辅助治疗对冠心病心力衰竭患者血管紧张肽II (AngII)水平和心功能的影响。方法:将128例患者分为两组,对照组64例,治疗组64例。对照组予常规治疗,治疗组患者在此基础上加用营心宁胶囊治疗,每次4粒,每日3次。治疗前及治疗8周后检测血浆AngII、脑钠肽(BNP),并行心脏彩色多普勒超声心动图测定左室射血分数(LVEF)、左室舒张末期内径(LVEDD)和每搏输出量(SV)。结果:治疗组和对照组总有效率分别为92.2%和89.1% (P > 0.01);显效率分别为43.8%,32.8% (P < 0.01)。两组治疗后患者的AngII、BNP、LVEF、LVEDD和SV均较治疗前明显改善(P < 0.01或P < 0.05),且治疗组患者的改善水平优于对照组(P < 0.01)。结论:营心宁胶囊能有效降低患者AngII水平,并对心功能有改善作用。

血管紧张素II对脓毒症休克大鼠心脏功能的影响

本研究拟通过盲肠结扎穿孔制备大鼠脓毒症模型,观察血管紧张素II对脓毒症休克(sepsis-shock)大鼠心脏功能的影响。方法 48只(Sprague-Dawley,SD)雄性大鼠随机分为6组(n=8):对照(control)组、假手术(sham)组、脓毒症休克(SS)组、去甲肾上腺素(NE)治疗组、血管紧张素II (ANGII)治疗组。采用盲肠结扎穿孔制备脓毒症休克动物模型。监测大鼠心率、血压变化。监测过程中大鼠如出现平均动脉压下降至65mmHg以下,立即给予0.9%生理盐水进行液体复苏,观察10分钟后如效果不佳,按照分组给予不同血管活性药物泵入。分别在造模后6,12,18,24小时抽血行心肌酶学指标检测,同时在该时段行超声观察大鼠心脏超声检查。于术后24小时留取心脏组织进行氧化因子指标测定,并进行心脏组织病理学观察。结果 与对照组和假手术组对比,脓毒症休克、去甲肾上腺素组、血管紧张素组平均动脉压下降明显,液体复苏效果欠佳,需要血管活性药物干预。与对照组和假手术组对比,脓毒症休克、去甲肾上腺素组、血管紧张素II组炎症反应、乳酸指标明显升高,具有统计学差异(P<0.05)。脓毒症休克组与对照组、假手术组相比,心脏左室射血分数(LVEF)明显下降,具有统计学差异(P<0.05),应用血管活性药物后,左室射血分数明显提高,血管紧张素II组射血分数提高与脓毒症组相比,具有显著统计学差异(P<0.01)。脓毒症休克组与对照组、假手术组相比,心肌酶学指标明显升高,应用去甲肾上腺素或血管紧张素II干预后,心肌酶学指标下降,与脓毒症组相比,具有统计学差异(P<0.05),血管紧张素II组改善更为明显(P<0.01)。结论 血管紧张素II可改善脓毒症休克对大鼠的心肌损害,对脓毒症休克大鼠心肌有一定的保护作用。

表达Strep-tag II的重组塞内卡病毒的构建与鉴定

为构建表达Strep-tag II的重组塞内卡病毒(SVA),本研究在感染性cDNA克隆p SVA-I212V/S460L的基础上,采用重叠延伸PCR扩增Strep-tag II并采用无缝克隆法将其插入SVA VP1基因C端,构建感染性cDNA克隆,命名为p SVA-Strep,并采用双酶切和测序鉴定正确后,将p SVA-Strep转染BHK-21细胞拯救重组病毒,收集病变细胞上清,并将含有病毒的细胞上清和野生型SVA(SVA-WT)分别感染BHK-21细胞,以未感染病毒的BHK-21细胞作为阴性对照,感染后24 h分别以鼠源SVA VP2蛋白单克隆抗体(MAb)5D10(1∶1000)、鼠源Strep-tag II MAb(1∶2000)作为一抗,以FITC标记的山羊抗小鼠Ig G(1∶2000)为二抗,采用间接免疫荧光试验(IFA)对重组病毒鉴定。IFA结果显示,以鼠源SVA VP2蛋白MAb 5D10为一抗,SVA-WT和重组病毒感染的细胞均出现绿色荧光,以Strep-tag II MAb作为一抗时,仅有重组病毒感染的细胞出现绿色荧光,经SVA-WT感染的BHK-21细胞及阴性对照细胞均无绿色荧光,表明拯救了Strep-tag II标记的重组病毒,并将其命名为r SVA-Strep。将r SVA-Strep在BHK-21细胞中连续传10代,每隔2代采用引物VP1-F/R经PCR鉴定并对第10代重组病毒的VP1基因测序以鉴定r SVA-Strep的遗传稳定性。结果显示,每隔两代的重组病毒经PCR扩增后均出现约780 bp的目的条带,第10代重组病毒扩增的VP1基因测序结果显示Strep-tag II基因仍在重组病毒中,且无基因突变,表明r SVA-Strep的遗传稳定性较强;将SVA-WT和r SVA-Strep分别以MOI 0.01感染BHK-21细胞,在感染后4 h、8 h、12 h、24 h、36 h、48 h和72 h收获病毒测定病毒滴度并绘制生长曲线,结果显示在病毒感染36 h内r SVA-Strep和SVA-WT生长动力学基本一致,表明Strep-tag II的引入在病毒感染36 h内对SVA的复制基本无影响。采用0.2%甲醛充分灭活r SVA-Strep,并利用Strep-TactinRXT Purification纯化试剂盒纯化该灭活病毒,将r SVA-Strep灭活病毒上清加至Strep-Tactin亲和层析柱,分别用不同体积洗脱缓冲液依次洗脱病毒并通过western blot鉴定病毒的纯化效果。对纯化过程中不同洗脱液洗脱病毒的western blot结果显示,不同体积的洗脱液中E1、E2和E3均出现VP0和VP2两条带,且E1和E2的条带最明显,表明洗脱缓冲液的最佳洗脱体积约为2.2 CV;以上结果表明r SVA-Strep可通过Strep-Tactin亲和层析柱一步法纯化。本研究在SVA中插入Strep-tag II标签,为SVA灭活疫苗的快速纯化提供技术手段,也为其他病原的快速纯化方法的建立提供参考。

基于NSGA-II遗传算法的定轴注射模具成型工艺参数优化

为解决注射成型过程中铸件的质量和铸造效率低等问题,提出一种NSGA-II算法和TOPSIS方法与响应面法相结合的新型注射工艺参数优化筛选方法。以定轴为研究对象,采用Box-Behnken设计,以熔体温度、模具温度、注射时间、保压压力为变量,以翘曲变形量和体积收缩率为响应变量,采用NSGA-II遗传算法对2个响应的目标函数执行优化,用TOPSIS方法求解优化得到的Pareto前沿解集,找到最优解。仿真结果表明,当注射时间为40.71s、模具温度为131℃、熔体温度为180.07℃、保压压力为65 MPa时,翘曲变形降低了10.92%、体积收缩率降低了11.19%。优化后的注射工艺参数可有效消除铸件内部收缩松动和缩孔缺陷,形成性能良好的致密铸件,提高了产品质量。

Fe(II)改性蒙脱石对土壤汞的吸附固定机理探究

为明确Fe-MMT对土壤汞离子(Hg^(2+))的吸附、解吸特性及潜在作用机理,采用FeSO_(4)·7H_(2)O改性钠基蒙脱土(Na-MMT),合成了Fe(II)基蒙脱石(Fe-MMT),并探究了不同pH值、吸附剂用量、Hg^(2+)初始浓度和反应时间等条件下,Fe-MMT对土壤Hg^(2+)的吸附解吸特性、吸附动力学和等温吸附模型。结果发现:在pH=5、吸附剂用量为0.5 g、Hg^(2+)初始浓度为170 mg/L、反应时间为0.5 h的条件下,Fe-MMT对土壤Hg^(2+)的去除率高达76.8%;Fe-MMT对Hg^(2+)+的吸附过程符合Langmuir等温吸附模型,伪二阶动力学模型可较好地拟合吸附动力学行为,表明该吸附过程主要为单分子层吸附,且主要发生在吸附剂表面的均相反应位点上;结合微观结构表征,发现Fe-MMT对土壤Hg^(2+)的吸附主要通过-S^(2-)、-SH和-OH与Hg^(2+)进行络合,以及Fe^(2+)与Hg^(2+)的原位共沉淀络合引起的;Fe-MMT在水-土混合体系中的解吸率为9.7%,表明Fe-MMT对土壤Hg^(2+)具有较强的固定作用。可见,Fe-MMT具有修复Hg污染土壤的潜力。

成人低角型安氏II类1分类与安氏II类2分类错合畸形矫治前唇颏形态差异性研究

通过对比成人低角型安氏II类1分类和安氏II类2分类错合畸形患者的面部形态特点及唇颏形态,为临床制定矫治方案和临床治疗工作提供思路。方法 分别选取低角型安氏I类1分类和安氏II类2分类错合畸形患者40例,男女比例为1:1,年龄:18-25岁.通过将侧貌X线片和面部90°面相重合,对测量面部软组织21项指标进行测量。结果 上唇突点—E线距离,下唇突点—E线距离,上唇倾角,下唇倾角,上唇厚度,上下唇面积对比均有统计学意义(P<0.05)。结论 低角型安氏II类1分类与安氏II类2分类相比,上下唇均呈前突状,上唇面积,安氏II类1分类较安氏II类2分类小,下唇面积,安氏II类1分类较安氏II类2分类大。

青霜露暴露治疗II度烧烫伤临床观察

目的:观察青霜露暴露治疗烧烫伤的临床效果。方法:门诊II度烧烫伤患者100例,其中浅II度67例,深II度33例。以暴露疗法在烧烫伤创面青霜露局部用药,每日1~3次,直至愈合。结果:67例浅II度烧烫伤创面经青霜露治疗全部愈合,愈合时间最短6天,最长30天;33例深II度烧烫伤创面经青霜露治疗30天痊愈31例,显效2例,愈合时间最短14天。所有创面愈合良好,局部疼痛消失和无明显增生性瘢痕。结论:青霜露治疗烧烫伤促进创面愈合,疗效确切;本方法简单方便,值得临床推广应用。

Hybrid treatment of varied orthodontic appliances for a patient with skeletal class II and temporomandibular joint disorders:A case report and review of literature

BACKGROUND The relation between orthodontic treatment and temporomandibular disorders(TMDs)is under debate;the management of TMD during orthodontic treatment has always been a challenge.If TMD symptoms occur during orthodontic treatment,an immediate pause of orthodontic adjustments is recommended;the treatment can resume when the symptoms are managed and stabilized.CASE SUMMARY This case report presents a patient(26-year-old,female)with angle class I,skeletal class II and TMDs.The treatment was a hybrid of clear aligners,fixed appliances and temporary anchorage devices(TADs).After 3 mo resting and treatment on her TMD,the patient’s TMD symptom alleviated,but her anterior occlusion displayed deep overbite.Therefore,the fixed appliances with TAD were used to correct the anterior deep-bite and level maxillary and mandibular deep curves.After the levelling,the patient showed dual bite with centric relation and maximum intercuspation discrepancy on her occlusion.After careful examination of temporomandibular joints(TMJ)position,the stable bite splint and Invisible Mandibular Advancement appliance were used to reconstruct her occlusion.Eventually,the improved facial appearance and relatively stable occlusion were achieved.The 1-year follow-up records showed there was no obvious change in TMJ morphology,and her occlusion was stable.CONCLUSION TMD screening and monitoring is of great clinical importance in the TMD susceptible patients.Hybrid treatment with clear aligners and fixed appliances and TADs is an effective treatment modality for the complex cases.

血管活性药物评分联合APACHE II评分对血流感染后脓毒性休克患者预后的预测价值

目的:探讨血管活性药物评分(vasoactive inotropic score, VIS)联合急性生理与慢性健康评分(APACHE II)对血流感染后脓毒性休克患者结局的预测价值,为临床提供参考。方法:采用回顾性研究方法,通过收集2020年1月至2022年12月安徽医科大学附属合肥医院重症医学科收治的185例脓毒性休克患者的临床资料,根据28 d转归情况,分为存活组95例和死亡组90例,记录所有患者性别、年龄、相关血液检测指标、SOFA评分、24小时内急性生理与慢性健康评分(APACHE II)及24小时内最大血管活性药物评分(VISmax24)等信息,采用单因素分析筛选脓毒性休克患者的相关危险因素,多因素logistic回归分析影响脓毒性休克患者预后的独立危险因素,采用受试者工作特征(receiver op-erating characteristic, ROC)曲线下面积(area under curve, AUC)分析各指标的诊断价值。结果:单因素分析结果表明:死亡组的APACHE II评分(24.30 ± 5.157)、VISmax24 [100.0 (53.5, 121.0)]明显高于存活组(P max24联合APACHE II评分(AUC = 0.848, 95% CI: 0.792~0.905),较单一的APACHE II评分(AUC = 0.729, 95% CI: 0.655~0.802)、VISmax24 (AUC = 0.783, 95% CI: 0.709~0.856)、乳酸(AUC = 0.665, 95% CI: 0.587~0.743)、SOFA (AUC = 0.680, 95% CI: 0.602~0.758)预测价值更高。结论:VISmax24联合APACHE II评分能更有效预测血流感染后脓毒性休克患者的预后。

磨削术在足踝部深II度烧伤治疗中的研究

探讨手术清创磨削技术与传统换药技术治疗足部烧伤的临床疗效。方法 抽取57例院内在2020年10月~2021年4月间(6个月)烧伤科接受诊疗的足踝部深II度烧伤患者进行回顾性分析,根据治疗方法进行分组,即行传统换药治疗(对照组28例,传统换药,去除分泌物及坏死组织,每日用生理盐水清洗创面后外敷复方多粘菌素B软膏)和行清创磨削技术治疗(治疗组29例,早期手术清创磨削技术后再采用异种生物辅料行创面封闭),评测对上述方案对足踝部深II度烧伤的治疗效果。结果 以清创磨削技术治疗的治疗组足踝部深II度烧伤患者,整体优良率上更加突出(100.00% 85.71%),并且极大程度缩短了愈合时间,促进整体病情的康复,同时还能有效防止创面加深、瘢痕增生以及换药感染(0.00%、0.00%、0.00% 78.57%、60.71%、17.86%),P<0.05。结论 清创磨削技术操作方法简单,容易推广,使早期足踝部烧伤创面的感染率降低,减轻患者痛苦,并提高愈合时间,值得推广。

维U颠茄铝镁片II+多潘立酮片治疗慢性胃炎对患者生活质量的改善探讨

探讨慢性胃炎患者经维U颠茄铝镁片II、多潘立酮片两者联用所得疗效,以及生活质量的改善情况。方法 80例患者均确诊“慢性胃炎”且在本校卫生所就诊,研究时段自2022年1月至2023年12月终止。依托随机性分组工具首先产生观察组,组内40例患者施行维U颠茄铝镁片II、多潘立酮片联合疗法;另外40例患者自然归入对照组,组内施行多潘立酮片单一疗法。分析治疗成效、首要症状、不良反应等多项数据,全方面印证两种疗法的差异性。结果 与对照组所统计数值相比,观察组在总疗效、生活质量(躯体疼痛、活力、情感职能、总体健康)方面显著处于更高水平(P<0.05);观察组患者首要症状(疼痛、恶心、烧灼感)消除相较于对照组更快(P<0.05),且组内统计不良反应发生率及半年内复发率依次为5.00%、2.50%,相较于对照组均处于较低水平(P<0.05)。结论 维U颠茄铝镁片II、多潘立酮片两者联用针对慢性胃炎疗效更为显著,患者首要症状能够尽早消除,从而恢复高质量生活,值得应用。

Biological function of miRNA-145-5p in angiotensin II induced renal inflammation

Objective:Chronic kidney disease(CKD)is a progressive disorder characterized by intricate structural and functional alterations in the kidneys,attributable to diverse causative factors.Notably,the therapeutic promise of miR-145-5p in addressing renal pathologies has been discerned.This investigation seeks to elucidate the functional role of miR-145-5p in injured kidneys by subjecting human glomerular mesangial cells(HGMCs)to stimulation with Angiotensin II(AngII).Materials and Methods:Cellular viability and the levels of inflammatory mediators were evaluated utilizing Cell Counting Kit-8(CCK-8),quantitative real-time polymerase chain reaction(qRT-PCR),and western blot methodologies,both in the presence of AngII incubation and in scenarios of miR-145p overexpression and downregulation.Furthermore,the cell cycle dynamics were elucidated through Fluorescence-activated Cell Sorting(FACS)analysis.Results:AngII incubation induced an upregulation of miR-145-5p and inflammatory factors including Intercellular Adhesion Molecule 1(ICAM-1),Interleukin 6(IL-6),Interleukin 8(IL-8),and Interleukin 1β(IL-1β).Additionally,it elevated the expression of Cyclin A2,Cyclin D1,and the G2/M cell cycle ratio.Conversely,inhibition of miR-145-5p heightened the levels of inflammatory factors and cell cycle regulators induced by AngII incubation.Reduced expression of miR-145-5p correlated with a downregulation of Interleukin 10(IL-10)expression,concurrently promoting HGMC proliferation under AngII stimulation.Moreover,ectopic miR-145-5p expression demonstrated a reduction in inflammatory factors,cell cyclin regulators,G2/M cell cycle ratio,and overall proliferation.Conclusion:MiR-145-5p exhibited inhibitory effects on the inflammatory response and proliferation induced by Angiotensin II in HGMCs,showcasing its potential as a therapeutic avenue for the treatment of kidney injury.

Nab-paclitaxel plus capecitabine as first-line treatment for advanced biliary tract cancers:An open-label,non-randomized,phase II clinical trial

BACKGROUND Biliary tract cancers(BTCs)are a heterogeneous group of tumors with high malignancy,poor prognosis,and limited treatment options.AIM To explore the efficacy and safety of nab-paclitaxel plus capecitabine as first-line treatment for advanced and metastatic BTCs.METHODS This open-label,non-randomized,double-center,phase II clinical trial recruited systemic therapy-naive patients with unresectable or metastatic BTCs between April 2019 and June 2022 at Beijing Cancer Hospital and the First Hospital of China Medical University.Eligible patients were administered nab-paclitaxel(150 mg/m^(2),day 1)and capecitabine(2000 mg/m^(2),twice daily,days 1-7)in 14-day cycles until experiencing intolerable toxicity or disease progression.The primary outcome was the objective response rate(ORR).The secondary outcomes included the disease control rate(DCR),overall survival(OS),progression-free survival(PFS),and safety.RESULTS A total of 44 patients successfully completed the trial,with a median age of 64.00 years(interquartile range,35.00-76.00),and 26(59.09%)were females.Tumor response assessment was impeded for one patient due to premature demise from tumor hemorrhage.Among the remaining 43 patients undergoing at least one imaging assessment,the ORR was 23.26%[95%confidence interval(CI):11.80%-38.60%],and the DCR was 69.77%(95%CI:53.90%-82.80%).The median OS was 14.1 months(95%CI:8.3-19.9),and the median PFS was 4.4 months(95%CI:2.5-6.3).A total of 41 patients(93.18%)experienced at least one adverse event(AE),with 10 patients(22.73%)encountering grade≥3 AEs,and the most frequent AEs of any grade were alopecia(79.50%),leukopenia(54.55%),neutropenia(52.27%),and liver dysfunction(40.91%),and no treatment-related deaths were documented.CONCLUSION Nab-paclitaxel plus capecitabine may be an effective and safe first-line treatment strategy for patients with advanced or metastatic BTCs.

Billroth II anastomosis combined with brown anastomosis reduce reflux gastritis in gastric cancer patients

BACKGROUND The surgeon performing a distal gastrectomy,has an arsenal of reconstruction techniques at his disposal,Billroth II among them.Braun anastomosis performed during a Billroth II procedure has shown evidence of superiority over typical Billroth II,in terms of survival,with no impact on postoperative morbidity and mortality.AIM To compare Billroth II vs Billroth II and Braun following distal gastrectomy,regarding their postoperative course.METHODS Patients who underwent distal gastrectomy during 2002-2021,were separated into two groups,depending on the surgical technique used(Billroth II:74 patients and Billroth II and Braun:28 patients).The daily output of the nasogastric tube(NGT),the postoperative day that NGT was removed and the day the patient started per os feeding were recorded.Postoperative complications were at the same time noted.Data were then statistically analyzed.RESULTS There was difference in the mean NGT removal day and the mean start feeding day.Mean total postoperative NGT output was lower in Braun group(399.17 mL vs 1102.78 mL)and it was statistically significant(P<0.0001).Mean daily postoperative NGT output was also statistically significantly lower in Braun group.According to the postoperative follow up 40 patient experienced bile reflux and alkaline gastritis from the Billroth II group,while 9 patients who underwent Christodoulidis G et al.Billroth II and Braun compared with Billroth II WJM https://www.wjgnet.com 2 March 20,2024 Volume 14 Issue 1 Billroth II and Braun anastomosis were presented with the same conditions(P<0.05).CONCLUSION There was evidence of superiority of Billroth II and Braun vs typical Billroth II in terms of bile reflux,alkaline gastritis and NGT output.

Impacts of angiotensin II on retinal artery changes in apolipoprotein E deficient mice

AIM:To investigate the impacts of angiotensin II(Ang II)on retinal artery changes in apolipoprotein E deficient(apoE^(-/-))mice.METHODS:ApoE^(-/-)male mice were infused by minipumps with Ang II at 1000 ng/kg·min(Ang II group)or saline(control group)for 28d.They were underwent ophthalmic fundus examination on day 0,14,and 28 of infusion.Histopathologic examination,ribonucleic acid(RNA)sequencing and local Ang II measurement of retinas were conducted.RESULTS:Ophthalmic fundus examination showed Ang II infusion promoted the formation of retinal arterial aneurysm-like lesions on day 28.Optical coherence tomography revealed the ganglion cell and inner plexiform layer(GCIPL)thickness in the control group was significantly thinner than that in Ang II group(P<0.001).Hematoxylin-eosin staining demonstrated diffused swelling of GCIPL layer and its disordered structure in Ang II group.Transmission electron microscopy showed Ang II infusion caused aggravation of atherosclerotic lesions,including increased swelling,roughness,disorganization of the retinal vasculature,and vacuoles formation.RNA-sequencing and gene ontology enrichment analysis demonstrated that the structure and function of cellular membrane might be disturbed and visual function might be compromised by Ang II.The local level of Ang II was higher in Ang II infusion group but did not show significant differences compared to the control group(P=0.086).CONCLUSION:Ang II infusion promotes the formation of retinal arterial aneurysm-like lesions in apoE^(-/-)mice,causing aggravation of atherosclerotic lesions,more severe disorganization of the retinal vasculature and disturbance of the cellular membrane.

Elimination of GGTA1,CMAH,β4GalNT2 and CIITA genes in pigs compromises human versus pig xenogeneic immune reactions

Background:Pig organ xenotransplantation is a potential solution for the severe organ shortage in clinic,while immunogenic genes need to be eliminated to improve the immune compatibility between humans and pigs.Current knockout strategies are mainly aimed at the genes causing hyperacute immune rejection(HAR)that occurs in the first few hours while adaptive immune reactions orchestrated by CD4 T cell thereafter also cause graft failure,in which process the MHCⅡmolecule plays critical roles.Methods:Thus,we generate a 4-gene(GGTA1,CMAH,β4GalNT2,and CIITA)knockout pig by CRISPR/Cas9 and somatic cell nuclear transfer to compromise HAR and CD4 T cell reactions simultaneously.Results:We successfully obtained 4KO piglets with deficiency in all alleles of genes,and at cellular and tissue levels.Additionally,the safety of our animals after gene editing was verified by using whole-genome sequencing and karyotyping.Piglets have survived for more than one year in the barrier,and also survived for more than 3 months in the conventional environment,suggesting that the piglets without MHCⅡcan be raised in the barrier and then gradually mated in the conventional environment.Conclusions:4KO piglets have lower immunogenicity,are safe in genomic level,and are easier to breed than the model with both MHCⅠandⅡdeletion.

Influence of Angiotensin II on α1-Adrenergic Receptors Function in Rat Aorta and Expression in Vascular Smooth Muscle Cells

Angiotensin II (Ang II) is the main mediator of the Renin-Angiotensin-System acting on AT1 and other AT receptors. It is regarded as a pleiotropic agent that induces many actions, including functioning as a growth factor, and as a contractile hormone, among others. The aim of this work was to examine the impact of Ang II on the expression and function of α1-adrenergic receptors (α1-ARs) in cultured rat aorta, and aorta-derived smooth muscle cells. Isolated Wistar rat aorta was incubated for 24 h in DMEM at 37˚C, then subjected to isometric tension and to the action of added norepinephrine, in concentration-response curves. Ang II was added (1 × 10−5 M), and in some experiments, 5-Methylurapidil (α1A-AR antagonist), AH11110A (α1B-AR antagonist), or BMY-7378 (α1D-AR antagonist), were used to identify the α1-AR involved in the response. Desensitization of the contractile response to norepinephrine was observed due to incubation time, and by the Ang II action. α1D-AR was protected from desensitization by BMY-7378;while RS-100329 and prazosin partially mitigated desensitization. In another set of experiments, isolated aorta-derived smooth muscle cells were exposed to Ang II and α1-ARs proteins were evaluated. α1D-AR increased at 30 and 60 min post Ang II exposure, the α1A-AR diminished from 1 to 4 h, while α1B-AR remained unchanged over 24 h of Ang II exposure. Ang II induced an increase of α1D-AR at short times, and BMY-7378 protected α1D-AR from desensitization.