Composition of Ophiopogon Polysaccharide, Notoginseng Total Saponins and Rhizoma Coptidis Alkaloids Inhibits Myocardial Apoptosis in Diabetic Atherosclerosis Rabbits

Objective: To investigate the effects of Composition of Ophiopogon polysaccharide, Notoginseng total saponins and Rhizoma Coptidis alkaloids (CONR) on myocardial apoptosis of diabetic atherosclerosis (DA) rabbits Methods: Sixty male New Zealand white rabbits were randomly divided into 6 groups [control group, model group, CONR high-dose group (450 mg/kg), CONR medium-dose group (150 mg/kg), CONR low-dose group (50 mg/kg), and simvastatin group] by using a completely random method, 10 in each group. DA model was established by intravenously injected alloxan combined with high-fat diet and abdominal aortic balloon injury. After mediation for 10 weeks, fasting blood glucose (FBG), glycosylated hemoglobin (GHB), glycosylated serum protein (GSP), fructoseamine (FRA), aldose reductase (AR), advanced glycation end products (AGEs) in serum were measured by enzyme linked immunosorbent assay (ELISA) method; the expression of receptor of AGEs (RAGE) in myocardial tissue were observed by immunohistochemical method; and p-Jun N-terminal kinase (p-JNK), caspase-3, B-cell lymphoma-2 (bcl-2) protein expression in myocardial tissue were measured by Western blotting. The myocardial apoptosis was detected by TdT-mediated dUTPnick-end labeling (TUNEL)method, and apoptosis index (AI) was calculated. Results: Compared with the control group, serum FBG, GHB, GSP, FRA, AR, AGEs and the expression of myocardium RAGE, p-JNK, caspase-3 proteins, as well as apoptosis index (AI) were significantly increased and bcl-2 protein was significantly decreased in the model group (P<0.01). Compared with the model group, the levels of serum FBG, GHB, GSP, FRA and AR showed a significant decline in CONR high- and medium-dose groups (P<0.01). FBG and GHB showed a significant decline in CONR low-dose group (P<0.01). Compared with the model group, the expression of serum AGEs and myocardium RAGE, p-JNK and caspase-3 protein as well as AI were significantly decreased and bcl-2 protein was significantly up-regulated in all treatment groups (P<0.01); high-dose CONR had the most significant effect on abovementioned indices compared with other treatment groups (P<0.01). Middle-dose CONR had better effect on serum AGEs compared with the low-dose group (P<0.01); middle-dose CONR and simvastatin groups had better effect on the expression of caspase-3, bcl-2 protein, myocardium apoptosis compared with the CONR low-dose group (P<0.01). Conclusion: CONR may effectively inhibit myocardial apoptosis on DA rabbits by intervening AGEs-RAGE and JNK, caspase-3, and bcl-2 protein expressions.     

重组人脑利钠肽对急性冠脉综合征伴心力衰竭患者的影响

目的 分析重组人脑利钠肽(rhBNP)对急性冠脉综合征(ACS)伴心力衰竭患者的影响。方法 选取2017年1月～2018年12月在本院接受治疗的ACS合并心力衰竭患者232例,随机数字表法分成对照组58例使用常规疗法和硝酸甘油治疗,治疗组174例使用常规疗法和rhBNP治疗;观察患者治疗前后神经内分泌激素和氨基末端脑钠尿肽(NT-proBNP)含量、心功能指标、6 min步行距离及治疗后发生心脏不良事件情况。结果 治疗后6 h治疗组患者血清醛固酮、肾上腺素、血管紧张素Ⅱ、肾素、去甲肾上腺素及NT-proBNP含量较治疗前、对照组降低(P0.05);治疗后1个月治疗组患者LVEF较治疗前、对照组升高,LVESV、LVEDV较治疗前、对照组降低(P0.05);治疗后1个月治疗组患者6 min步行距离较治疗前、对照组升高,治疗后6个月治疗组心脏不良事件发生率低于对照组(P0.05)。结论 rhBNP可显著改善ACS合并心力衰竭患者心功能指标,降低血清神经内分泌激素、NTproBNP含量和心脏不良事件发生率。     

基于标准YY0505-2012的监护类医疗器械患者耦合电缆传导抗扰度测试方法分析

射频场感应的传导骚扰抗扰度试验是医用电气设备的一项重要检验项目,基于YY 0505-2012对GB/T 17626.6中条款进行的修改和补充,本文旨在研究传导抗扰度试验中监护类医疗器械患者耦合电缆单根试验布置和成束试验布置的差异,为患者耦合电缆传导抗扰度试验探究可靠的试验布置方法。文中对传导骚扰抗扰度试验的标准和原理作了概述,分别对监护类医疗器械患者耦合电缆的单根试验布置和成束试验布置进行传导抗扰度测试,文中所选受试设备在两种测试布置状态下均出现不能通过测试的结果,测试现象存在差异。通过对两种试验布置结果进行分析和总结,综合考虑临床使用的风险性和试验结论的可靠性,本文建议监护类医疗器械的患者耦合电缆在传导抗扰度试验时两种试验布置均要进行测试,以确保患者耦合电缆在最不利的状态下试验。本文通过试验数据的分析和总结,为患者耦合电缆的传导抗扰度试验布置方法提供了规范性参考。     

Non-clinical pharmacokinetics and pharmacodynamics of rVIII-SingleChain,a novel recombinant single-chain factor VIII

Introduction

rVIII-SingleChain (CSL627), a novel recombinant coagulation factor VIII (FVIII), is under investigation in a phase I/III clinical programme (AFFINITY) for the treatment of haemophilia A. Non-clinical studies were conducted to investigate the pharmacokinetic/pharmacodynamic profile of rVIII-SingleChain in comparison with full-length recombinant FVIII.

Materials and Methods

Binding affinity of rVIII-SingleChain for von Willebrand factor was investigated by surface plasmon resonance analysis. The pharmacokinetic profile of rVIII-SingleChain was compared with a marketed full-length recombinant FVIII concentrate (Advate^®) in haemophilia A mice, von Willebrand factor knock-out mice, Crl:CD (SD) rats, rabbits and cynomolgus monkeys. Systemic FVIII activity or antigen levels were recorded. Procoagulant activity was measured in an FeCl₃-induced arterial occlusion model and by recording thrombin generation activity (ex vivo) after administration of 200–250 IU/kg rVIII-SingleChain or full-length FVIII to haemophilia A mice.

Results

rVIII-SingleChain displayed a high affinity for von Willebrand factor (K_D = 44 pM vs. 139 pM for full-length recombinant FVIII). In all animal species tested, rVIII-SingleChain had more favourable pharmacokinetic properties than full-length recombinant FVIII: clearance was decreased and area under the curve and terminal half-life were enhanced vs. full-length recombinant FVIII, while in vivo recovery and volume of distribution were equivalent. rVIII-SingleChain showed a prolonged thrombin generation potential and prolonged procoagulant activity vs. full-length recombinant FVIII in an FeCl₃-induced arterial occlusion model.

Conclusions

rVIII-SingleChain had a higher affinity for von Willebrand factor than full-length recombinant FVIII and displayed favourable pharmacokinetic/pharmacodynamic properties in non-clinical models.     

The defects in development and apoptosis of cardiomyocytes in mice lacking the transcriptional factor Pax-8

Backgroud

Cardiac-specific deletion of ALK3 is lethal in mid-gestation with ventricular septum malformations (VSM). This study was designed to define the Pax-8's role in heart development and cardiomyocyte apoptosis.

Methods

Pathologic changes in the hearts of Pax-8 or ALK3 knockout and wild type control mice were determined by light and electron microscopy. Analysis of cardiomyocyte apoptosis was performed by TUNEL. The effect of Pax-8 gene deficiency on caspase-3 activity was examined after transfecting Pax-8 siRNA into cultured myoblast cell line.

Results

Mice with ALK3 or Pax-8 gene knockout but not wild type control animals showed the development of VSM. Increased cardiomyocyte apoptosis was found in homozygotes. Echocardiography showed that Pax-8 homozygote mice developed malfunction of the heart. Furthermore, the caspase-3 activity was significantly higher in the cells treated with Pax-8 siRNA as compared to those treated with negative control siRNA in H9C2 (2-1) cell line.

Conclusions

The Pax-8 gene may play a crucial role in heart development and regulating cardiocyte apoptosis. Knockout of Pax-8 may exert a similar effect on myocardial morphology and apoptosis as those seen in ALK3 knockouts. Furthermore, the ventricular septum malformations could be partially attributed to accelerated cardiomyocyte apoptosis.     

通过ROC曲线评估联合检测TnI、hs-CRP和NT-proBNP对老年急性冠状动脉综合征的诊断价值

目的:通过ROC曲线探讨肌钙蛋白I(TnI)、超敏C反应蛋白(hs-CRP)和N末端脑利钠肽前体(NT-proBNP)联合检测在老年急性冠状动脉(冠脉)综合征(ACS)临床诊断中的应用价值。方法:收集不稳定型心绞痛(UA组,60例)、非ST段抬高型心肌梗死(NSTEMI组,61例)、ST段抬高性心肌梗死(STEMI组,59例)患者及健康者(对照组,60例)血清样本,用化学发光免疫法检测TnI,电化学发光免疫法检测NT-proBNP,速率散射免疫比浊法测定hs-CRP;绘制ROC曲线并建立Logistic回归模型,分析各指标单独和联合检测在UA、NSTEMI及STEMI诊断中的作用。结果:除UA组TnI外,ACS 3个组中血清TnI、hs-CRP与NT-proBNP值显著高于对照组(P<0.05);与单独检测相比,3项指标联合检测时,UA组、NSTEMI组和STEMI组ROC曲线下面积(AUC)[(0.858±0.051)、(0.988±0.013)和(0.998±0.004)]最大,灵敏度(57.8%、95.9%和99.1%)和特异度(94.7%、100.0%和100.0%)也最好。结论:联合检测TnI、hs-CRP和NT-proBNP有助于老年ACS中UA的诊断,对NSTEMI与STEMI的灵敏度和特异度也能达到最优化,但对区分NSTEMI和STEMI效果不明显。     

基于GIS的南昌县血吸虫病疫情聚集区域综合探测研究

目的探测江西省南昌县血吸虫病疫情聚集区范围。方法收集2009年南昌县血吸虫病流行区血吸虫感染率数据,采用ArcGIS 9.2软件中空间聚集性分析、全局自相关以及空间热点探测方法,绘制空间自相关系数图,描述不同空间距离尺度下的血吸虫感染率自相关指数变化趋势;结合实际情况,以代表性的距离为空间关系参数,对研究区域的血吸虫感染率热点区域进行探测。结果2009年研究区域内的血吸虫感染空间分布具有明显的聚集性;从自相关系数图发现在空间距离尺度为1 900、2 600、3 800 m和5 000 m时出现了波峰;结合研究区域地理环境,发现在空间距离尺度为5 000 m的血吸虫病热点区域更符合实际,存在2个热点区域和2个次热点区域。结论空间聚集性分析结合空间自相关分析能够更加精确地探测血吸虫病疫情聚集区域。     

Activation of c-Jun N-terminal kinase in non-cancerous liver tissue predicts a high risk of recurrence after hepatic resection for hepatocellular carcinoma

Aim: Hepatocellular carcinoma (HCC) ranks as the third leading cause of cancer deaths worldwide. Hepatic resection is the mainstay of curative treatment for early stage HCC. Although c‐Jun N‐terminal kinase (JNK) activation contributes to hepatocyte proliferation and HCC development in mice, the extent of involvement of JNK in human HCC development is unknown. The aim of this study is to assess the predictive value of JNK for postoperative recurrence in HCC. Methods: From April 2005 to March 2008, 159 patients underwent curative resection for HCC. From the 159 patients, 20 patients each matched for age, gender and etiology were registered as three groups: (i) without recurrence (no recurrence group), (ii) with recurrence within one year after surgery (early recurrence group), and (iii) with recurrence at one year or more after surgery (late recurrence group) (a cross‐sectional control study). We investigated factors contributing to postoperative early and late phase recurrence. Results: Multivariate analysis using a Logistic regression model showed that JNK activity in non‐cancerous liver tissue was correlated with postoperative late recurrence. (P = 0.02, odds ratio; 5.79, 95% confidence interval [CI]; 1.33–25.36). Conclusions: JNK activity in non‐cancerous liver tissue is considered as a reliable predictive biomarker for post‐operative recurrence in HCC.     

High-acuity GIS mapping of private practice dental services in New Zealand: does service match need?

Objectives: New Zealand is a country with a relatively small population (4 million people) distributed unevenly over a relatively large land area. Adult oral health services in New Zealand are almost all delivered through a market‐driven, private practice model and are funded directly by patient payments. Little attention has been given to the distribution of these services. This study reports the findings of a high‐acuity examination of the distribution of private dental practices in New Zealand, using modern geographic information system (GIS) tools. Methods: A total of 1,045 private dental practices in New Zealand were geocoded. These dental practices overlaid 1,909 area units. Results: The highest practice : adult population ratios found in this study reflected the areas with the highest population densities of Maori and Pacific Islander people. Conclusions: Oral health has a substantial impact on health‐related quality of life and the utilisation of dental care services can contribute to its improvement. As such, it is expected that access to care should be focused on the population groups with the highest degree of need. However, in a market‐driven, mostly private practice model, such as that in New Zealand, available care is concentrated largely in areas of high socioeconomic status and in populations with lower levels of oral disease.