A combination of a thrombin inhibitor and dexamethasone prevents the development of experimental disseminated intravascular coagulation in rats

INTRODUCTION: Disseminated intravascular coagulation (DIC) is a serious and potentially lethal complication of severe sepsis. DIC is characterised primarily by widespread platelet aggregation and fibrin deposition, followed by consumption of platelets, coagulation factors, and inhibitors. The aim of the study was to evaluate the efficacy of the active-site thrombin inhibitor melagatran, the active form of the oral direct thrombin inhibitor ximelagatran, in reducing fibrinogen and platelet consumption in blood and fibrin deposition in organs, in an experimental endotoxinaemia rat model. MATERIALS AND METHODS: In this model, DIC was induced by an intravenous injection of endotoxin (1 mg/kg). Melagatran was compared with unfractionated heparin and the synthetic glucocorticoid analogue dexamethasone. Animals were divided into 16 treatment groups in which high and low doses of each agent were tested alone and in combination with melagatran. RESULTS: Fibrinogen consumption was reduced by melagatran, dexamethasone, and heparin, and was completely prevented by melagatran in combination with dexamethasone. Platelet consumption was partially reduced by melagatran, unfractionated heparin, and dexamethasone, but complete protection was observed only with melagatran in combination with dexamethasone. Melagatran in combination with dexamethasone or heparin protected the liver and spleen from fibrin deposition. CONCLUSION: In this experimental DIC rat model, the direct thrombin inhibitor melagatran given together with dexamethasone protected against the consequences of activated haemostasis.     

叶下珠复方Ⅱ号对小鼠H22肝癌移植瘤生长的抑制作用

目的观察叶下珠复方Ⅱ号对小鼠H22肝癌移植瘤生长的抑制作用,并探讨其可能的作用机制。方法取昆明小鼠40只,建立小鼠H22肝癌移植瘤模型,分为模型组、叶下珠复方Ⅱ号高剂量组（37.5g/kg）、低剂量组（18.75g/kg）和环磷酰胺（20mg/kg）治疗组。叶下珠复方Ⅱ号高、低剂量组均灌胃给药,环磷酰胺组采用腹腔注射,每日1次,连续8d。末次给药24h后,测定瘤体质量,计算抑瘤率;检测血清IL-2和TNF-а含量。结果叶下珠复方Ⅱ号高、低剂量组瘤重明显低于模型组,差异均有显著性意义（P〈0.01）,但与环磷酰胺组比较,差异均无显著性意义（P〉0.05）。叶下珠复方Ⅱ号高、低剂量组的抑瘤率分别为67%和58%,与环磷酰胺组接近。叶下珠复方Ⅱ号高剂量组血清IL-2水平明显高于模型组（P〈0.05）。叶下珠复方Ⅱ号高、低剂量组血清TNF-а水平明显低于模型组,差异有显著性意义（P〈0.05）。结论叶下珠复方Ⅱ号有较好的抑制小鼠H22肝癌移植瘤生长作用,作用机制与调节免疫,升高IL-2水平和抑制TNF-а水平有关。     

小檗碱衍生物CPU 86017抑制KV1.5电流（IKur）及对抗SD大鼠房颤作用

目的：研究小檗碱衍生物CPU86017对抗房颤作用及其离子通道机制。方法：运用膜片钳技术在稳定表达人心房肌Kv1.5钾通道细胞系（HEK293）及豚鼠心房肌细胞上观察CPU86017对超速整流钾通道（IKur）的作用,观察CPU86017（1.25或2.5mg·kg-1）对比阳性药azimilide（3mg·kg^-1）对乙酰胆碱（ACh）和CaCl2诱发的大鼠房颤的治疗作用。结果：CPU86017依浓度抑制IKur,对豚鼠心房肌细胞和培养的HEK293细胞上IKur的半数抑制浓度（IC50）分别是4.56和0.21μmol·L^-1。在乙酰胆碱（ACh）和CaCl2诱发的房颤模型上,CPU86017有效缩短房颤持续时间,逆转房颤所致心房有效不应期（AERP）的缩短。结论：CPU86017能抑制KV1.5编码的电流IKur,改善房颤大鼠心房ERP的病变,有效对抗房颤。     

武警哨兵国产CPU 芯片集成多生理参数及环境信息智能监测系统的设计与应用研究

 目的 利用信息化途径构建起武警哨位与执勤监控站点,以及上级管理站点间武警哨兵生理信号参数、环境信息参数监测信息初筛,为武警监管站点提供直观的哨兵的生理状态及环境状况预警。方法 应用大数据和人工智能,设计一套基于国产CPU芯片的武警哨兵集成多生理参数及环境信息的智能监测系统,对在一个集成融合的监控中心实现对武警哨兵的生理信号参数和哨位环境信息参数进行实时监测分析。结果 通过该系统的建设最大限度地依托国产CPU芯片进行开发,极大地优化了信息安全手段,提高对武警哨兵的多途径实时有效看护,武警监管站点能及时根据参数的改变和预警判断哨兵身体突发状况,及时给出处置方案,严防武警哨兵在执勤过程中的意外事件发生。结论 实现对武警哨兵的生理信号参数和哨位环境信息参数进行实时监测分析 ,为执勤监控站点及上级管理站点预警。     

Abrupt changes in FKBP12.6 and SERCA2a expression contribute to sudden occurrence of ventricular fibrillation on reperfusion and are prevented by CPU86017

Aim： The occurrence of ventricular fibrillation （VF） is dependent on the deterioration of channelopathy in the myocardium. It is interesting to investigate molecular changes in relation to abrupt appearance of VF on reperfusion. We aimed to study whether changes in the expression of FKBP12.6 and SERCA2a and the endothelin （ET） system on reperfusion against ischemia were related to the rapid occurrence of VF and whether CPU86017, a class III antiarrhythmic agent which blocks Ikr.IKs. and ICa.L, suppressed VF by correcting the molecular changes on reperfusion. Methods： Cardiomyopathy （CM） was produced by 0.4 mg/kg sc L-thyroxin for 10 d in rats, and subjected to 10 min coronary artery ligation/reperfusion on d 11. Expressions of the Ca^2＋ handling and ET system and calcium transients were conducted and CPU86017 was injected （4 mg/kg, sc） on d 6-10. Results： A high incidence of VF was found on reperfusion of the rat CM hearts, but there was no VF before reperfusion. The elevation of diastolic calcium was significant in the CM myocytes and exhibited abnormality of the Ca^2＋ handling system. The rapid downregulation of mRNA and the protein expression of FKBP12.6 and SERCA2a were found on reperfusion in association with the upregulation of the expression of the endothelin-converting enzyme 0ECE） and protein kinase A （PKA）, in contrast, no change in the ryanodine type 2 receptor （RyR2）, phospholamban （PLB）, endothelin A receptor （ETAR）, and iNOS was found. CPU86017 removed these changes and suppressed VE Conclusion： Abrupt changes in the expression of FKBP12.6, SERCA2a, PKA, and ECE on reperfusion against ischemia, which are responsible for the rapid occurrence of VF, have been observed. These changes are effectively prevented by CPU86017.     

CPU0213, a non-selective ETA/ETB receptor antagonist, improves pulmonary arteriolar remodeling of monocrotaline-induced pulmonary hypertension in rats

1. The aim of the present study was to explore the effects of CPU0213, a dual endothelin ET(A)/ET(B) receptor antagonist, and nifedipine, a calcium antagonist, in relieving pulmonary hypertension (PH). Both endothelin receptor and calcium antagonists have been reported to be effective in alleviating the remodelling of pulmonary arteries induced by monocrotaline (MCT) in rats. 2. After an initial single dose of 60 mg/kg, s.c., MCT, CPU0213 was administered to rats at doses of 25, 50 or 100 mg/kg, p.o., for 28 days. In addition, nifedipine was administered to another group of rats at a dose of 10 mg/kg, p.o., for 28 days. The haemodynamics of the right ventricle, pulmonary vascular activity, remodelling of the pulmonary arterioles (< 150 microm) and biochemical changes were evaluated. 3. Right ventricular systolic pressure (RVSP), central venous pressure (CVP), the maximum rate of uprising pressure (dP/dT(max)) and the weight index of the right ventricle were significantly elevated in MCT-treated rats. In addition, increases in pulmonary endothelin-1, malonyldialdehyde (MDA) and hydroxyproline content and a reduction in superoxide dismutase activity was found after MCT treatment. The thickness and area of the pulmonary arterial wall were significantly increased in MCT-treated rats compared with control rats. At all three doses tested, CPU0213 ameliorated these changes in a dose-dependent manner and the effects were associated with a greater reduction in the remodelling of pulmonary arterioles. However, nifedipine was only partially effective in amelerioating biochemical and haemodynamic changes induced by MCT, significantly reducing RVSP, CVP, +dp/dt(max), tissue MDA, inducible nitric oxide synthase and hydroxyproline content, increasing -dp/dt(min) and having no effect on the other parameters investigated. In addition, nifedipine had no effect on remodelling of the arterial wall. 4. In conclusion, CPU0213 is more effective than nifedipine in suppressing the remodelling of pulmonary arterioles in PH induced by MCT treatment of rats. Furthermore, CPU0213 may have promise in treating PH secondary to connective tissue disease.     

F52-8C北京万东程控500mA X线机ERR11故障成因分析

目的：CPU控制的普放设备在本世纪之初早就已经进入到基层医疗组织,如何能够利用故障代码进行分析,最快尽短时间的查出故障,减少损失,是本文最大的目标。方法：分析ERR11故障的所有可能成因,并讲解相关检测方法。结果：从多个方面分析该故障的成因,避免遗漏。结论：掌握原理分析可以为维修节省大量的时间,不可忽视实践的重要性但是也不能忽视理论分析的作用,维修结束做好维修总结是一个良好的维修习惯。     

CPU0213通过抑制ET系统和NF-κB通路改善感染性休克大鼠血管活性

目的:通过观察CPU0213对感染性休克大鼠血管活性的改善,探讨其治疗感染性休克可能的作用机制。方法:感染性休克大鼠术后8 h皮下给予CPU0213(30 mg.kg-1,bid×3 d)。记录存活率,血流动力学参数,器官脏器系数和腹腔渗出液重量,检测血浆ET-1和血清iNOS、GSH-PX、SOD、MDA含量及胸主动脉血管活性,肠系膜血管NF-κB、TNF-αi、NOS和ET系统mRNA表达及其激活态NF-κB蛋白表达。结果:模型组大鼠存活率和平均动脉压明显降低,心率和器官脏器系数明显增加,腹腔渗出液显著增多,ET-1和iNOS、MDA含量明显增加,GSH-PX和SOD活性显著下降,血管功能明显降低,TNF-αi、NOS和ET系统mRNA表达及NF-κB的蛋白表达明显增加;CPU0213治疗后,上述指标均有不同程度改善。结论:CPU0213通过阻断ET系统和NF-κB通路改善血管活性,减少腹腔渗出液,提高存活率。     

CPU86017及其旋光异构体对L-甲状腺素致大鼠心肌病异常的calcineurin和NFκB基因表达的抑制作用

目的研究CPU86017及其旋光异构体对L-甲状腺素致大鼠心肌病异常的calcineurin和 NFκB基因改变,并比较CPU86017及其旋光异构体对它们的作用.方法大鼠随机分成7组,每日给予L-甲状腺素(0.2 mg·kg-1, sc) 共 10 d 造成心肌病模型,CPU86017及其旋光异构体(SR、SS、RS、RR)(4 mg·kg-1, sc)在 d 6 连续给药 5 d.动物处死后测定心脏指数,取大鼠心脏测定心肌组织中氧化应激指标,NO和iNOS的活力,大鼠左心室心肌Calcineurin、NF-κB的基因表达由半定量逆转录酶PCR方法测定.结果L-甲状腺素致大鼠心肌病模型组心肌明显肥大,氧化应激增强,NO含量减少,iNOS活力增强,Calcineurin和NF-κB基因表达上调.给予CPU86017及其旋光异构体能不同程度地改善心肌中NO含量及iNOS活力,减轻氧化应激,可以下调这些基因的表达,其中SR比其它旋光异构体疗效好.结论Calcineurin 和NF-κB可能对L-甲状腺素所致大鼠心肌病中细胞内钙调节起着重要的作用,CPU86017及其旋光异构体SR对L-甲状腺素所致大鼠心肌病具有保护作用,该作用与抑制心肌Calcineurin、NF-κB基因的表达、抑制NOS及抗氧化有关.