低分子肝素与灯盏细辛注射液联合治疗不稳定型心绞痛疗效观察

目的:观察低分子肝素与灯盏细辛注射液联合治疗不稳定型心绞痛(UAP)的疗效。方法:将96例UAP患者随机分为常规治疗对照组和加用低分子肝素和灯盏细辛注射液治疗组各48例进行疗效观察。结果:10d后总有效率治疗组为91.7%,对照组为68.8%(P <0.01);观察4周总心血管事件发生率治疗组明显低于对照组(P <0.05);治疗组未发现明显不良反应。结论:在常规治疗的基础上加用低分子肝素和灯盏细辛注射液,能更有效地控制心绞痛发作,显著降低近期心血管事件的发生率。     

应用血栓弹力图评价血液透析患者低分子肝素剂量的研究

目的探讨应用血栓弹力图评价血液透析患者低分子肝素剂量的临床研究。方法选取2018年1月至2019年8月在广东省佛山市三水区人民医院进行血液透析患者200例,根据低分子肝素应用总量不同分为对照组(高剂量组,总量≥80U/kg体重)和研究组(低剂量组,总量<80U/kg体重),分别在透析前、透析3h及透析完成24h时段对两组患者活化部分凝血活酶时间(activated partial thromboplastin time,APTT)及血栓弹力图指标进行对比分析,比较两组抗凝效果,对比两组静脉压、跨膜压等指标变化情况,通过监测患者血浆尿素浓度对透析效果进行评价。结果与对照组比较:患者透析前APTT检测结果差异无显著性(P>0.05),血栓弹力图检测中R值、MA值、K值、CI值结果差异无显著性(P>0.05);透析3h后,两组患者APTT明显延长且差异无显著性(P<0.05),研究组R值、MA值、K值、CI值较对照组差异有显著性(P<0.05);透析完成24h后,两组APTT明显延长且差异有显著性(P<0.05),研究组APTT小于对照组;透析患者低分子量肝素剂量与患者体重的ROC曲线下面积为0.68时即可达到充分抗凝效果;研究组较对照组出血倾向低,差异有显著性(P<0.05),两组静脉压、跨膜压、透析效果比较差异无显著性(P>0.05)。结论血栓弹力图指标更能反映透析患者凝血实时功能,低分子肝素小剂量应用即可达到充分抗凝且不影响透析效果,透析患者使用小剂量低分子量肝素出血风险更低。     

Cost and utility of a low-molecular-weight heparin and unfractionated heparin for treatment of deep venous thrombosis in a Balkan country: A model analysis

OBJECTIVE: Low-molecular-weight heparins are cost-saving for treating venous thrombosis in developed countries, but their cost-effectiveness in developing Balkan countries has not been investigated. The objective of the present study was to evaluate whether the results of cost-effectiveness studies of low-molecular-weight heparins versus unfractionated heparin for treatment of acute deep venous thrombosis conducted in a developed country are applicable to Serbian socioeconomic circumstances. METHODS: A Markov model was constructed based on the decision model used by Gould et al (Ann Intern Med 1999;130:789-99), with the help of TreeAge Software (TreeAge Software Inc, USA). Probabilities for clinical outcomes were obtained from that study, while the costs were derived from the Serbian Republic Institute for Health Insurance and other sources. Patients with acute deep venous thrombosis, 60 years of age, were introduced into the model. A Monte Carlo microsimulation trial with 1000 patients was used for drawing conclusions from the model. The time horizon was six years, and the Serbian Republic Institute for Health Insurance was used. RESULTS: Enoxaparin for treatment of deep venous thrombosis in Serbian patients was not cost-saving, but was a cost-effective therapeutic strategy (from 5,322.97 CSD [Serbia and Montenegro dinars] per quality-adjusted life-year gained when used in out-patients, to 10,929.76 CSD per quality-adjusted life-year gained when used in inpatients). The drug acquisition cost was the major factor influencing the cost-effectiveness, due to the low cost of labour and hospitalization. CONCLUSIONS: The results of pharmacoeconomic studies performed in developed countries cannot be directly extrapolated to developing Balkan countries. However, enoxaparin is still a cost-effective strategy for the treatment of deep venous thrombosis.     

低分子肝素对脑梗死患者甲襞微循环的动态影响及疗效观察

目的观察低分子肝素(Low molecular weight heparin,LMWH)对脑梗死(Cerebral infarction,CI)患者甲襞微循环的动态影响和疗效。方法按入院的先后随机将入选的CI病例分为LMWH组和对照组。LMWH组(n=25)予LMWH5000抗XaIU腹壁皮下注射,2次/d,共7d;对照组(n=30)予阿司匹林肠溶片口服,100mg/d。LMWH组患者分别于LMWH注射前和治疗后1h、2h、3h、4h、5h、6h、7h、治疗后第8天检查甲襞微循环,对照组分别于治疗前和治疗后第8天检查甲襞微循环。两组患者治疗前、治疗后第8天进行神经功能缺损程度评分和疗效评定。结果与治疗前比较,LMWH组治疗后2h～5h甲襞微循环总积分明显下降(P<0.01),尤其以治疗后3h最明显。LMWH组、对照组的总有效率88%和60%,两者差异有统计学意义(P<0.05)。两组治疗前后的神经功能缺损评分、甲襞微循环总分对比差异有统计学意义(P<0.05或P<0.01),LMWH组治疗前后神经功能缺损评分、甲襞微循环总分减分率分别为0.60±0.33和0.32±0.26,两者呈正相关(r=0.47,P<0.05)。结论LMWH可有效改善CI患者的微循环状态,改善其神经功能和预后,是CI早期治疗的有效手段之一。     

经皮冠状动脉介入治疗中静脉注射不同剂量那屈肝素的抗血栓疗效比较

目的比较冠状动脉介入治疗术(PCI)中静脉注射2种不同剂量那屈肝素的抗血栓疗效,明确取得理想抗血栓疗效的最佳剂量.方法采用前瞻性、随机、双盲的设计,共入选42例因患冠心病需行PCI术的患者,随机分为小剂量那屈肝素组(0.075 ml/10 kg)及大剂量组(0.1 ml/10 kg).PCI术前静脉注射那屈肝素,分别在注射前、注射后8 min、1 h、2 h和4 h,用发色底物法测定血浆抗Ⅹa因子活性.同时还观察了出血指数(定义为PCI治疗术后24 h内血红蛋白的下降值)及30 d内出血事件.结果 (1)小剂量组注射那屈肝素前、注射后8 min及1 h血浆抗Ⅹa因子活性分别为(0.10±0.00) IU/ml、(1.89±0.24) IU/ml、(0.96±0.24) IU/ml,均与大剂量组相应时间点的血浆抗Ⅹa因子活性[分别为(0.10±0.00) IU/ml,(1.89±0.30) IU/ml,(0.93±0.14) IU/ml]相似(P值分别为0.162、0.962和0.702).那屈肝素注射后2 h及4 h,小剂量组抗Ⅹa因子活性[分别为(0.47±0.13) IU/ml和(0.30±0.12) IU/ml]低于大剂量组[分别为(0.75±0.14) IU/ml和(0.45±0.08) IU/ml,P值均小于0.001]. (2)小剂量组的出血指数(3.3±3.8)g/L与大剂量组(0.2±6.4)g/L相似(P=0.061).(3)二组30 d内均未发现根据TIMI试验标准确定的大出血或轻度出血,均未发生死亡、心绞痛复发、心肌梗死及需行血管再通术等临床事件.结论 PCI术前注射二种剂量的那屈肝素均能达到理想的抗血栓效果,其中小剂量组能维持其有效的抗血栓疗效1 h,大剂量组能维持长达2 h的抗血栓效果.     

Anti-Proliferation Activity of Fucoidan in MKN45 Gastric Cancer Cells and Downregulation of Phosphorylated ASK1, a Cell Cycle-Regulated Kinase

Background

Fucoidan is a high-molecular polysaccharide whose main constituent is sulfated fucose. We specifically focused on the anti-proliferation activity of fucoidan and examined the underlying mechanism in MKN45 gastric cancer cells.

Methods

MKN45 cell proliferation was analyzed by BrdU assay and fucoidan cytotoxicity was examined by LDH and clonogenic assays. The Agilent Human microarray kit was used to identify upregulated and downregulated genes in response to fucoidan, and western blot analyses evaluated cell cycle proteins.

Results

Fucoidan impeded the MKN45 cell cycle by approximately 50%, and inhibited cell proliferation.LDH assays showed no immediate cytotoxic effects of fucoidan at 24 h exposure, however longer time courses revealed cell growth inhibition at 4 days in a dose-dependent manner. Microarray analysis identified MAP3K5, or ASK1 (apoptosis signal-regulating kinase),which was upregulated by 1.38-fold upon fucoidan treatment.Fucoidan increased ASK1 protein levels, while reducing phosphorylated ASK1 levels. Reduction of ASK1 by siRNA decreased proliferation of MKN45 cells.

Conclusion

Our findings show that fucoidan may suppress cellular proliferation and DNA synthesis in MKN45 cells by suppressing the ASK1-p38 signaling pathway through reduction of phosphorylated ASK1 levels.     

低分子肝素联用酚妥拉明改善肺心病急性加重期患者心肺功能的研究

目的 为了提高慢性肺源性心脏病(简称肺心病)急性加重期患者心肺功能,探究低分子肝素联用酚妥拉明对于改善心肺功能的有效性.方法 选取2012年9月-2014年9月在绍兴第二医院进行治疗的慢性肺源性心脏病急性加重期患者120例,分为观察组和对照组,并且入院后都进行常规治疗.观察组60例患者在常规治疗的基础上进行低分子肝素与酚妥拉明联用;对照组60例患者给予参麦注射液治疗.治疗1个疗程后分析比较2组咳嗽、气喘及肺部哕音、心功能和血气的变化情况.结果 治疗后,观察组显效26例,有效28例,无效6例,总有效率为90.0％.对照组显效14例,有效31例,无效15例,总有效率为75.0％.观察组患者疗效明显好于对照组,2组总有效率比较差异有统计学意义(P＜0.05).观察组患者PaO2由治疗前的(56.3±8.5) mm Hg增加到(83.2 ±9.2)mm Hg,PaCO2由治疗前的(73.4±10.2)mm Hg降低到(54.2±9.4) mm Hg;对照组患者PaO2由治疗前的(56.9±8.2) mm Hg增加到(75.6±9.4)mm Hg,PaCO2由治疗前的(74.1 ±10.6)mm Hg降低到(66.8±9.3)mm Hg.由此可以看出观察组的治疗效果明显好于对照组.2组患者在治疗前后对比差异具有统计学意义(P＜0.05).结论 低分子肝素与酚妥拉明联用能够有效改善慢性肺源性心脏病急性加重期患者的心肺功能,并且效果良好,值得临床推广应用.     

中西医结合预防髋周骨折术后深静脉血栓形成

目的探讨中西医结合预防髋周骨折术后下肢深静脉血栓（DVT）形成的临床疗效及安全性。方法根据入选标准对100例髋周骨折手术的患者分成两组。其中治疗组56例,联合采用基本预防、物理预防与药物（中西医结合）预防措施;对照组44例,仅采用基本预防的措施。主要的观察指标：①术后48 h的术口引流量;②术后血小板计数变化情况;③术前及术后双下肢彩色多普勒检查结果。结果治疗组DVT 5例（8.9%）,对照组DVT 14例（31.8%）,两组DVT发生率差异有统计学意义（P〈0.05）。两组患者术后48 h的术口引流量及术后血小板计数,差异无统计学意义（P〉0.05）。结论中西医结合（丹红注射液、低分子肝素联合间隙充气加压装置）能有效降低髋周骨折术后DVT的发生率,并发症少,在预防髋周骨折术后DVT的发生有着良好的社会及经济效益。     

褐藻多糖硫酸酯减轻1-甲基-4-苯基吡啶离子引起的细胞损伤和氧化应激

目的以1-甲基-4-苯基吡啶离子(1-methyl-4-phenylpyridinium,MPP+)为工具药处理MN9D细胞,建立帕金森病(Pakinson’s disease,PD)的细胞模型,观察褐藻多糖硫酸酯对细胞的保护作用,并初步探讨其作用机制。方法用不同浓度(25、50、100、200μmol/L)的MPP+处理MN9D细胞36h,50μmol/L MPP+处理MN9D细胞,时间分别为12、2436、48h,建立细胞损伤模型。用0.01、0.1、1g/L褐藻多糖硫酸酯预孵育MN9D细胞1h后,加入50μmol/L MPP+共同作用36h以探讨褐藻多糖硫酸酯的保护作用。MTT法检测细胞活力、生化法测定乳酸脱氢酶(LDH)释放量,并采用二氯荧光素乙二酯(DCF-DA)染色法检测细胞内的氧化应激水平。结果随着MPP+浓度增加或作用时间延长,MN9D细胞MTT值逐渐降低。50μmol/L MPP+处理细胞36h,MTT值明显下降,LDH释放量增加。而0.1、1g/L的褐藻多糖硫酸酯预孵育1h,可明显减轻MN9D细胞的损伤,提高MTT值并降低LDH释放量,细胞形态学改变与生化实验结果一致。50μmol/L MPP+作用12h,可使MN9D细胞的氧化应激水平明显升高,而0.1、1g/L的褐藻多糖硫酸酯预处理1h,可以拮抗MPP+引起的细胞内氧化应激水平增高。结论褐藻多糖硫酸酯可以有效拮抗MPP+对MN9D细胞的损伤作用,其机制可能与褐藻多糖硫酸酯具有抗氧化活性有关。     

不同时间窗低分子肝素治疗脑梗死患者的疗效观察

目的观察低分子肝素（low-molecular-weightheparin,LMWH）在不同时间窗治疗脑梗死（cerebral infarction,CI）的临床疗效。方法75例入组患者按起病至治疗开始时间分为A组（〈24h）、B组（24-48h）、C组（49h～7d）,每组25例。3组患者均使用LMWH 5000抗XaIU腹壁皮下注射,2次／d,共7d,于治疗前、治疗后第8天进行神经功能缺损程度评分和疗效评定。结果3组患者治疗后的神经功能缺损评分均降低（P〈0．05）,治疗前后神经功能缺损评分差值比较差异有统计学意义（P〈0．05）,A组大于C组（P〈0．01）;3组总有效率比较差异有统计学意义（P〈0．05）,A组高于C组（P〈0．05）。结论LMWH在不同时间窗均可改善CI患者的神经功能缺损和预后,其疗效以24h内为佳。