Experimental therapeutic effect of combined cytokines on beagle dogs exposed to 4.5 Gy γ-rays

Objective To evaluate the effects of combined administration of recombinant human interleukin-11(rhIL-11),recombinant human G-CSF(rhG-CSF)and recombinant human interleukin-2 (rhIL-2)on acute radiation sickness(ARS)beagles.Methods Sixteen beagle were irradiated with 4.5 Gy60 Co γ-rays to establish ARS models,and were divided into irradiation control group,supportive care group and combined cytokines treatment group.After irradiation irradiation control group was given no treatment,the dogs in supportive care group received purely symptomatic treatment,while combined cytokines treatment group received rhIL-11 50μg/(kg·d)and rbG-CSF 10μg/(kg·d)subcutaneously(0-14 d)and rhIL-2 1×1 06 U/d(29-43 d)besides symptomatic treatment.Manifestation and characteristics of ARS beagles were observed,and the survival time were recorded.At last,post-mortem examination and histological examination were performed.Results All animals underwent nausea,diarrhea and fever.After irradiation,all animals in irradiation control group died in two weeks,and the mean survival time was 12.7 d,while only one died at 33 d in supportive care group.All dogs in combined cytokine group survived at 45 day after exposure,and their haematopoiesis and gastrointestinal tract were recovered.Conclusions Combination of rhIL-11 + rhG-CSF + rhIL-2 treatment could be significantly effective on ARS beagles irradiated by 4.5 Gy60 Co γ-rays,which could accelerate injured haemotopoiesis and intestinal tract recovery,increase the survival rate and improve the life quality of animals.     

Initial research of screening for the differentially expressed proteins in beagles irradiated with 4.5 Gy60 CO γ-rays by two-dimensional gel electrophoresis and mass spectrometry

Objective To explore the mechanisms of cytokines on acute radiation disease in irradiated beagles.Methods The sera of beagles irradiated with 4.5 Gy γ-rays with cytokines treatment was collected at different time points post irradiation.The two-dimensional gel electrophoresis(2-DE)was used to isolate and compare the differentially expressed proteins in sera.HD-MS was used to analyze the differentially expressed proteins with significance,and the amino acid sequences should be determined. Results High resolution 2-DE gel map was obtained.There were six differentially expressed proteins in sera of irradiated beagles at different time points.Four protein spots were successfully identified by MS.A significant spot was identified as serum amyloid A(SAA)by HD-MS,with relative molecular mass of 13 077 and isoelectfie point of 6.26.Expression of SAA was not found 1 d pre-irradiation and 36 d postirradiation,but increased slightly 1 d(0.2166)and significantly 14 d post-irradiation(0.4577). Conclusions The expression of serum amyloid A was consistent with the process of acute radiation injury,which might indicate the turnover of the disease.     

Clotting mechanism in beagles irradiated by 4.5 Gy γ-rays

Objective To explore the clotting mechanism in beagles irradiated by 4.5 Gy γ-rays after treatment with supportive care,or supportive care and combined cytokines.Methods Sixteen beagles were divided into irradiation control group,Supportive care group and combined cytokines treatment group.Platelet aggregation test,thrombelagtography (TEG) and the time measurement were analyzed in vitro.Results In irradiation group and supportive care group,the platelet aggregation rates in beagles were decreased markedly and the k value of TEG was increased 7 d post-irradiation,while those indexes in combined cytokines treatment group changed little.At 14 d post-irradiation,each parameter of TEG in irradiated group changed obviously.The values of r,k,r+k and M were elevated significantly,clotting time and the maximum coagulation time of thrombus delayed,the Ma value was decreased markedly,and the maximum elasticity amplitude of thrombus was diminished.All parameters in combined cytokines treatment group were better than those in supportive care group.The thrombin time was prolonged obviously in irradiated group 14 d post-irradiation,while the thrombin time was the longest at 2-3 weeks post irradiation in supportive care group and combined cytokines treatment group(P>0.05).Conclusions Cytokines could improve the platelet aggregation and the blood clotting functions of beagles suffering from acute radiation sickness.     

标杆管理在临床护理质量管理中的实践与应用

标杆管理（benchmarking）,亦称参照管理、基准管理,是20世纪90年代以来在国际企业中最流行、最具战略思想的管理方法之一,与企业再造、战略联盟并称三大管理方法。标杆管理可分为三大类：内部标杆管理一以医院内部最优秀科室和员工为基准的标杆管理;竞争标杆管理一以行业领先者为基准的标杆管理;流程标杆管理一以其他企业的最佳工作流程为基准的标杆管理。     

Therapeutic effects of combined cytokines on hematopoietic injuries induced by 4.5 Gy γ-rays irradiation in beagles

Objectivc To observe the therapeutic effects of combined cytokines on hematopoietic injuries induced by 4.5 Gy60 Co γ-rays irradiation in beagles,and to provide experimental evidences for the clinical treatment of extremely severe myeloid acute radiation sickness(ARS).Methods 16 beagles were given 4.5 Gy60 Co γ-rays total body irradiation,and then randomly assigned into irradiation control group,supportive care group and cytokines group.In addition to supportive care,recombinant human granulocyte colony-stimulating factor (rhG-CSF),recombinant human interleukin-11(rhIL-11)and recombinant human interleukin-2(rhIL-2)were administered subcutaneouly to dogs in cytokines group.Peripheral blood hemogram was examined once every two days.Bone marrow and peripheral blood were collected to proceed colony cultivation 4 d pre-irradiation and 1 and 45 d post-irradiation.Conventional histopathological sections of sternum were prepared to observe the histomorphology changes. Results After irradiation,the population of all kinds of cells in peripheral blood declined sharply.WBC nadir Was elevated(1.04×109/L,but 0.28×109/L and 0.68×109/L for the irradiation control group and the supportive care group separately),the duration of thrombocytopenia was shortened (24 days,but 33 days for the supportive care groug) and red blood cell counts were maintained in the range of normal values after cytokincs treatment in combination.The colony forming efficiency of haemopoietic stem cells(HSCs)in bone marrow and peripheral blood decreased obviously 1 d post irradiation,but recovered to the level of that before irradiation 45 d post irradiation after supportive care and cytokines treatment.Hematopoietic cells disappeared in bone marrow of animals in irradiation control group,but hematopoietic functions were recovered after cytokines were administrated.Conclusions RhG-CSF.rhIL-11 and rhIL-2 used in combination could elevate WBC nadir,accelerate the recovery of leukocytes,platelets and red blood cells and promote the proliferation,differentiation and maturity of HSPCs left in the body after 4.5 Gy γ-rays total body irradiation,eventually restore the hematopoietic function.Hence,combination of rhG-CSF,rhIL-11 and rhIL-2 could serve as better therapeutic strategy to treat extremely severe myeloid ARS.     

rhIL-11对急性放射病小鼠小肠上皮细胞凋亡及相关基因表达的影响

目的通过研究重组人白介素11(rhIL-11)对照射小鼠小肠上皮细胞凋亡及相关基因表达的影响,探讨IL-11在急性放射病小鼠小肠上皮细胞辐射损伤中的治疗作用以及相关机制。方法利用琼脂糖凝胶电泳法和原位末端标记法检测rhIL-11对8．0Gy^60Coγ射线照射小鼠小肠上皮细胞凋亡的影响,通过免疫组织化学的方法观察Bcl-2和Bax的表达变化。结果rhIL-11治疗和预防给药可明显地抑制小鼠小肠上皮细胞凋亡的发生,并诱导Bcl-2表达而使Bax表达明显减弱。结论rhIL-11可能通过影响Bcl-2和Bax的表达而抑制辐射引起的小肠上皮细胞凋亡,从而产生防护作用。     

两例极重度骨髓型放射病肺组织病变的病理学对比观察及分析

目的对比观察不同吸收剂量、不同存活时间对极重度骨髓型放射病肺组织病变发生发展的影响.方法分别于病人死亡后从肺脏取材,每个尸检病例从不同部位取材数块,10%甲醛固定,石蜡包埋,病理组织切片,分别行HE和Gimsa染色,光学显微镜观察和分析.结果极重度骨髓型伴轻度肠型放射病尸检病例（107号）肺内主要病变为肺组织大面积坏死伴广泛性曲霉菌感染;另一极重度骨髓型放射病尸检病例（108号）肺内主要病变为广泛性卡氏肺孢子虫感染,虫体充满肺泡腔,肺泡间隔增宽,成纤维细胞活跃增生伴胶原纤维形成.结论放射病抢救治疗过程中肺内容易继发霉菌或卡氏肺孢子虫感染,可能与病人的呼吸衰竭和早期死亡有直接关系;极重度骨髓型放射病人的存活时间超过2个月,早期肺纤维化过程开始启动.     

应用品管圈降低急诊预检分诊中MEWS评分的不准确率

目的:探讨品管圈活动在降低急诊预检分诊中改良早期预警评分(MEWS)不准确率的效果.方法:成立品管圈,针对分诊中MEWS评分进行现状把握、原因分析、设定目标值、拟定对策并加以实施.结果:MEWS评分的不准确率活动前为5.81%,活动后为2.48%,活动前后比较,差异有统计学意义(P<0.01).结论:开展品管圈活动能显著降低急诊预检分诊中MEWS评分的不准确率.     

甲酰化肽样受体介导脂多糖诱导的白细胞趋化反应及虎杖甙的调节作用研究

目的：初步研究虎杖甙（PD）对脂多糖刺激下白细胞趋化活性调节的机制。 方法： 用趋化小室方法测定虎杖甙对LPS刺激下多形核白细胞（PMN）趋化活性及转染了甲酰化肽样受体（FPRL1）基因的293细胞（FPRL1/293）趋化活性的影响。 结果： LPS及LPS刺激的PMN上清可增强多形核白细胞的趋化反应；同样LPS刺激下转染了甲酰化肽样受体基因的293细胞的趋化性显著升高。而PD可下调LPS刺激引起的PMN和FPRL1/293细胞的趋化性升高。 结论： 甲酰化肽样受体FPRL1可能参与介导脂多糖引起的白细胞趋化反应，PD可能通过抑制白细胞趋化因子的分泌和下调甲酰化肽样受体活性来调节细胞的趋化性。     

虎杖甙对LPS刺激下平滑肌细胞蛋白激酶C活性的影响

目的通过观察虎杖甙(PD)对LPS刺激(模拟感染性休克)平滑肌细胞内蛋白激酶C活性的影响,探讨虎杖甙抗休克和调节血管平滑肌细胞收缩性的机制.方法取培养的大鼠主动脉平滑肌细胞,用DE-52纤维素层析方法初步提纯PKC,用组蛋白IIIS作为底物,用同位素闪烁计数的方法测量其活性(PKC活性单位用fmol·mg