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1.
目的 探讨芪归糖痛宁颗粒对糖尿病周围神经病变(Diabetic Peripheral Neuropathy,DPN)的作用机制。 方法 大鼠高脂饲料喂养4周后,空腹12h进行链脲佐菌素(STZ)60 mg/kg一次性腹腔注射复制DPN大鼠模型,将成模的大鼠分组,分别予以相应药物灌胃,正常对照组和模型组实验期间予以生理盐水灌胃,疗程12周,实验结束后,分别对大鼠FPG、神经传导速度、血清SOD、MDA、NGF水平及坐骨神经AGEs、PARP mRNA的表达进行检测。 结果 与模型组比较,芪归糖痛宁颗粒高、低剂量组均能降低糖尿病大鼠血糖(P<0.01或P<0.05),改善神经传导速度(P<0.01或P<0.05),均降低血清MDA水平(P<0.05),均降低坐骨神经AGEs、PARP mRNA的表达(P<0.01)。芪归糖痛宁颗粒高剂量组升高血清SOD水平(P<0.01),降低血清NGF水平(P<0.01)。 结论 芪归糖痛宁颗粒通过抑制氧化应激与AGEs、PARP途径的相互作用,从而防治和延缓糖尿病周围神经病变的发生。  相似文献   

2.
目的观察芪归糖痛宁颗粒对大鼠糖尿病周围神经病变(diabetic peripheral neuropathy,DPN)的疗效,并探讨其作用机制。方法以链脲佐菌素(streptozotocin,STZ)一次性腹腔注射复制DPN大鼠模型。于模型复制第3天起,各治疗组分别灌胃给予相应的受试药物,正常组和模型组灌胃给予等容量溶媒,疗程8周。实验结束后,测定大鼠热痛阈值、血液流变学指标、血清神经生长因子(nerve growth factor,NGF)、髓磷脂碱性蛋白(myelin basic protein,MBP)的含量,同时取固定部位坐骨神经,用苏木精-伊红染色观察坐骨神经组织病理学变化。结果与模型组比较,芪归糖痛宁颗粒组能明显改善DPN大鼠坐骨神经病理组织学损伤程度,同时降低大鼠热痛阈(P<0.05),降低大鼠全血黏度低切、中切、高切,血浆黏度,红细胞聚集指数及MBP含量(P<0.05,或P<0.01),升高血清NGF含量(P<0.05)。结论芪归糖痛宁颗粒对大鼠DPN具有一定的治疗作用。  相似文献   

3.
目的 观察芪蛭皱肺颗粒对慢性阻塞性肺疾病(COPD)大鼠血清、支气管肺泡灌洗液(BALF)中白细胞介素-8(IL-8)和肿瘤坏死因子-α(TNF-α)水平的影响.方法 采用香烟烟熏加气管内注入脂多糖的复合因素造模法建立COPD大鼠模型,于造模第15天,空白组、模型组给予等体积中剂量颗粒辅料溶液灌胃4周,其他各药物干预组给予芪蛭皱肺颗粒小剂量、中剂量、大剂量和阳性药物(固本咳喘片)溶液灌胃4周,末次用药后取肺组织HE染色,取血清和BALF采用放免法检测IL-8和TNF-α的含量.结果 采用香烟烟熏加气管内注入脂多糖的方法成功复制了COPD大鼠模型,病理观察显示大鼠支气管及肺血管壁炎细胞浸润,分泌物明显增多,肺泡扩张.与空白组比较,模型组血清IL-8与TNF-α含量均升高(P<0.01或<0.05);BALF IL-8与TNF-α含量亦均升高(P<0.05或<0.01);与模型组比较,芪蛭皱肺颗粒各剂量组及固本咳喘片组血清及BALF中IL-8和TNF-α含量均降低(P<0.05),以芪蛭皱肺颗粒大剂量组降低更明显(P<0.01).结论 芪蛭皱肺颗粒有可能是通过减少炎症因子的生成和释放,从而有效调节肺炎症损伤时IL-8和TNF-α水平的升高,对大鼠模型气道炎症具有一定的干预作用.  相似文献   

4.
【目的】探讨补阳还五汤对糖尿病周围神经病变(DPN)大鼠的止痛作用及机制。【方法】将60只大鼠分为正常组,模型组(MNCV)和感觉神经传导速度(SNCV),中药低、中、高剂量组,中药高剂量+H-89[蛋白激酶A(PKA)抑制剂]组,每组10只。除正常组,其他各组大鼠采用高脂高糖饲料饲喂结合腹腔注射链脲佐菌素(STZ)法构建DPN模型。给药结束后,检测大鼠足热痛阈值,测定大鼠运动神经传导速度(MNCV)和感觉神经传导速度(SNCV),免疫组织化学法观察表皮内神经纤维密度(IENF),酶联免疫吸附分析(ELISA)检测血清空腹胰岛素(FINS)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、胰岛素抵抗指数(HOMA-IR),白细胞介素(IL)-1β、IL-6、肿瘤坏死因子α(TNF-α),血管内皮生长因子(VEGF)、血管生成素1(Ang-1)、CD34水平,坐骨神经组织中环磷酸腺苷(cAMP)浓度,Western Blot法检测坐骨神经组织中PKA和反应元件结合蛋白(CREB)表达水平。【结果】与正常组比较,模型组足热痛阈值,TC...  相似文献   

5.
目的探讨在慢性阻塞性肺疾病(简称慢阻肺)大鼠模型中姜黄素增强糖皮质激素抗炎作用的效果和机制。方法将24只sD大鼠随机分为慢阻肺组、姜黄素组、布地奈德组和姜黄素+布地奈德组。所有大鼠均采取单纯香烟烟熏法复制慢阻肺大鼠动物模型。实时定量PCR检测大鼠肺组织中的白细胞介素8(IL-8)、单核细胞趋化蛋白1(MCP-1)、肿瘤坏死因子α(TNF-α)、基质金属蛋白酶9(MMP-9)、组蛋白脱乙酰化酶2(HDAC2)的mRNA表达,酶联免疫吸附试验(ELISA)检测大鼠肺组织中的IL-8、MCP-1、TNF-α表达,蛋白免疫印迹(Western)检测大鼠肺组织中MMP-9、HDAC2的蛋白表达,染色质免疫沉淀(CHIP)检测IL-8、MCP-1、TNF-α、MMP-9启动子区与HDAC2的结合水平。结果与慢阻肺组、姜黄素组、布地奈德组比较,姜黄素+布地奈德组大鼠肺组织中IL-8、MCP-1、TNF-α、MMP-9的mRNA和蛋白表达量均降低,HDAC2的表达量升高。CHIP结果显示,与慢阻肺组、姜黄素组、布地奈德组比较,姜黄素+布地奈德组大鼠肺组织的IL-8、MCP-1、TNF-α、MMP-9启动子区与HDAC2的结合水平升高。结论姜黄素和布地奈德合用大鼠肺组织中IL-8、MCP-1、TNF-α、MMP-9的表达量明显降低,并与HDAC2的表达量呈负相关,这种相关性可能与大鼠肺组织的IL-8、MCP-1、TNF-α、MMP-9启动子区与HDAC2的结合水平有关。说明姜黄素可能通过升高HDAC2的表达量和活性,增强慢阻肺大鼠对糖皮质激素的敏感性及抗炎作用。  相似文献   

6.
目的:观察宁痫颗粒联合卡马西平对海人酸难治性癫痫大鼠血清IL-1β、IL-6、TNF-α水平的影响,探讨其作用机制.方法:Wistar雄性大鼠42只,按体质量随机分为假手术组、模型组、卡马西平+宁痫颗粒高(0.03+4.80/g·kg-1·d-1)、中(0.03+2.40/g·kg-1·d-1)、低剂量组(0.03+ 1.20/g·kg-1·d-1)、宁痫颗粒组(2.40/g· kg-1·d-1)和卡马西平组(0.03/g· kg-1·d-1),每组6只.采用海马CA3局部注射海人酸制作大鼠癫痫模型,术后第二天予苯妥英钠药物筛选14d后成功制作难治性癫痫模型.各组分别灌胃2周后股动脉采血,收集各实验组大鼠血清,采用免疫酶联法(Elisa法),测定各实验组大鼠血清IL-1β、IL-6、TNF-α水平.结果:与卡马西平组比较,宁痫颗粒低剂量联合卡马西平组大鼠血清IL-1β、IL-6含量显著降低(P<0.05),宁痫颗粒中、高剂量组联合卡马西平大鼠血清IL-1β、IL-6含量极显著降低(P<0.01);宁痫颗粒低、中、高剂量联合卡马西平组大鼠血清TNF-α含量极显著降低(P<0.01).结论:IL-1β、IL-6、TNF-α共同参与了免疫反应,其水平的变化间接反映了脑组织损伤程度.表明宁痫颗粒联合卡马西平具有一定的免疫抑制作用,比单用卡马西平疗效显著,说明两者联合具有协同作用,其机制可能是通过抑制炎症反应从而阻断癫痫发作,达到治疗癫痫目的.  相似文献   

7.
目的探讨芪归糖痛宁颗粒对糖尿病周围神经病变(DPN)的作用机制。方法 SD大鼠65只,随机留取10只为空白对照组,其余55只给予高脂饲料喂养4周后,空腹12h链脲佐菌素(STZ)60mg/kg一次性腹腔注射复制DPN大鼠模型,将42只成模大鼠分为模型组(M组)9只、芪归糖痛宁颗粒高剂量组(QTG高组)、芪归糖痛宁颗粒低剂量组(QTG低组)和甲钴胺片组(J组)组各11只,分别予以相应药物灌胃,空白对照组(Con组)和模型组实验期间予以生理盐水灌胃,疗程12周,实验结束后,分别对大鼠空腹血糖(FPG)、神经传导速度、血清超氧化物歧化酶(SOD)、丙二醛(MDA)、神经生长因子(NGF)水平及坐骨神经糖基化终末产物(AGEs)、聚ADP核糖聚合酶(PARP)基因的表达进行检测。结果治疗后,与模型组(M组)比较,芪归糖痛宁颗粒高(QTG高组)、低剂量(QTG低组)组均能降低糖尿病大鼠血糖[(14.08±3.54)mmol/L、(16.11±2.95)mmol/L比(20.41±2.25)mmol/L,P0.01或P0.05)],改善神经传导速度(49.16±5.37)m/s、(43.76±3.93)m/s比(39.66±3.65)m/s,P0.01或P0.05)],降低血清MDA水平(14.91±1.23)nmol/L、(15.22±0.55)nmol/L比(16.75±1.67)nmol/L,P均0.05)],降低坐骨神经AGEs m RNA的表达(0.572±0.021,0.983±0.013比1.088±0.032,P均0.01),降低PARP m RNA的表达(0.677±0.035、0.829±0.015比1.113±0.024,P0.01);与模型组(M组)比较,芪归糖痛宁颗粒高剂量组升高血清SOD水平(112.87±4.98)U/m L比(97.55±4.93)U/m L,P0.01),升高血清NGF水平[(37.38±4.51)ng/L比(26.06±4.41)ng/L,P0.01)]。结论芪归糖痛宁颗粒通过抑制氧化应激与AGEs、PARP途径的相互作用,从而防治和延缓大鼠糖尿病周围神经病变的发生。  相似文献   

8.
目的 探讨温针灸、谢氏点穴及其联合治疗对肥胖大鼠膝骨关节炎的治疗效果与作用机制。〖JP1〗方法 采用高脂饮食诱导肥胖大鼠膝骨关节炎,检测温针灸、谢氏点穴以及温针灸+谢氏点穴治疗后肥胖大鼠体质量,血清总胆固醇(total cholesterol,TC)、三酰甘油(total triglyceride,TG)、高密度脂蛋白(high-density lipoprotein,HDL)与低密度脂蛋白(low-density lipoprotein,LDL),膝关节病变,关节滑液中白细胞介素1β(interleukin 1β, IL-1β)、肿瘤坏死因子α(tumor necrosis factor α,TNF-α)、单核细胞趋化蛋白1(monocyte chemoattractant protein-1,MCP-1)和血管内皮生长因子(vascular endothelial growth factor,VEGF)的含量以及膝关节软骨层中基质金属蛋白酶-1(matrix metalloproteinases-1,MMP-1)和MMP-13表达的水平。结果 与对照组比较,模型组大鼠体质量,血清TC、TG、LDL水平,膝关节Mankin得分,关节滑液中IL-1β、TNF-α、MCP-1、VEGF水平及膝关节软骨层中MMP-1与MMP-13的表达水平均显著升高(P<0.05),血清HDL水平显著降低(P<0.05)。与模型组比较,各治疗组大鼠血清TC、TG水平,膝关节Mankin得分,关节滑液中MCP-1、VEGF水平及膝关节软骨层中MMP-13表达水平均显著下降(P<0.05)。谢氏点穴疗法、温针灸+谢氏点穴疗法显著升高大鼠血清HDL水平,降低关节滑液中TNF-α含量和膝关节软骨层中MMP-1表达水平(P<0.05);温针灸+谢氏点穴疗法显著降低大鼠血清LDL水平、关节滑液中IL-1β含量(P<0.05);温针灸+谢氏点穴疗法降低大鼠血清TC、TG、LDL水平,膝关节Mankin得分及膝关节软骨层中MMP-1、MMP-13表达水平显著优于温针灸治疗组和谢氏点穴治疗组(P<0.05)。结论 温针灸联合谢氏点穴能够调节脂质代谢,减少关节滑液中VEGF与MCP-1的分泌,从而缓解高脂饮食诱导的膝骨关节炎。  相似文献   

9.
目的 研究益气活血通络方含药血清对高糖诱导的人脐静脉内皮细胞(human umbilical vein endothelial cells, HUVECs)炎性因子白细胞介素-1β(interleukin-1 beta, IL-1β)、肿瘤坏死因子-α(tumor necrosis factor alpha, TNF-α)、单核细胞趋化蛋白-1(monocyte chemoattractant protein-1, MCP-1)及金属基质蛋白酶-1(metal matrix proteinase-1, MMP-1)表达的影响,探讨益气活血通络方对脐静脉内皮细胞的保护作用。方法 选择SD大鼠30只,中药灌胃,制备含药血清。体外培养HUVECs,MTT法检测不同时间点、不同浓度葡萄糖对细胞存活率的影响;将HUVECs随机分为5组,即空白对照组,模型组,益气活血通络方低、中、高浓度组,高糖刺激后,分别加入不同浓度益气活血通络方含药血清干预,收集上清及细胞,ELISA法检测IL-6的表达,Western Blot法测定IL-1β、TNF-α、MCP-1及MMP-1蛋白的表达。结果 细胞培养48 h 后,33.3 mmol/L高糖组(模型组)细胞活力显著降低(P<0.05);高糖刺激可引起IL-6、IL-1β、TNF-α、MCP-1及MMP-1蛋白的高表达(P<0.05),益气活血通络方含药血清显著抑制IL-6、IL-1β、TNF-α、MCP-1及MMP-1蛋白的高表达(P<0.05)。结论 益气活血通络方可抑制炎性因子的高表达,对高糖损伤的HUVECs有一定的保护作用。  相似文献   

10.
小檗碱对2型糖尿病周围神经病变大鼠IL-1β、TNF-α的影响   总被引:3,自引:1,他引:2  
目的:通过观察小檗碱(Ber)对糖尿病周围神经病变(DPN)模型大鼠血清、脊髓及坐骨神经内白介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)的浓度的影响,探讨小檗碱治疗DPN作用机制。方法:以链脲佐菌素(STZ)腹腔注射诱导形成DPN模型,以不同剂量100mg/kg、187.5mg/kg的Ber灌胃治疗,每天1次,持续8周。用酶联免疫吸附测定(ELISA)法分别测定各组大鼠血清、脊髓及坐骨神经内IL-1β、TNF-α的浓度。结果:Ber对DPN大鼠痛阈、坐骨神经传导速度(NCV)有明显改善(P<0.05),与对照组比较,DPN模型组大鼠的IL-1β、TNF-α含量显著增高(P<0.05),Ber治疗8周后,与DPN模型组比较IL-1β、TNF-α含量明显降低(P<0.05)。结论:抑制细胞炎症因子IL-1β、TNF-α的释放,可能是小檗碱改善DPN的机制之一。  相似文献   

11.
Objective: To evaluatel the value of D-dimers in patients with acute aortic dissection (AAD). Methods: This study consisted of 16 patients with AAD and 27 non-AAD patients. Serum D-dimets were measured by Sta-Liatest D-DI immunoturbidimetric assay. Results: D-dimer level was higher (P < 0.001) in patients with AAD(7.91 ± 5.52 μg/ml) than that in non- AAD group(1.57±1.24 μg/ml). D-dimer was positive (>0.4 μg/ml) in all patients with AAD and in 10 control group patients (37%). Among patients with acute AAD, D-dimers tended to be higher in Stanford A than in Stanford B (8.67 ± 4.31 μg/ml vs. 3.24±1.27 μg/ml, P <0.01). D-dimer values tended to be higher in more extended disease(3.84 ± 1.65 μg/ml, 8.57 ± 3.58 μg/ml and 11.87 ± 5.69 μg/ml in thoracic aorta, thoracic and abdominal aorta, thoracic and abdominal aorta and iliacal arteries, respectively, P < 0.05 for both 8.57 ± 3.58 and 11.87 ± 5.69 vs. 3.84 ± 1.65 ). Including the control group into the analysis, we found a sensitivity of 100%, a negative predictive value of 100%, and a specificity of 66% and a positive predictive value of 64% for D-dimer in diagnosis of AAD in our patients with suspected AAD. Conclusion: D-dimer was elevated in patients with AAD. A negative D-dimer test result could be useful in excluding AAD.  相似文献   

12.
Objective: To set up a simple and reliable rat model of combined liver-kidney transplantation. Methods: SD rats served as both donors and recipients. 4℃ sodium lactate Ringer's was infused from portal veins to donated livers,and from abdominal aorta to donated kidneys, respectively. Anastomosis of the portal vein and the inferior vena cava (IVC) inferior to the right kidney between the graft and the recipient was performed by a double cuff method, then the superior hepatic vena cava with suture. A patch of donated renal artery was anastomosed to the recipient abdominal aorta. The urethra and bile duct were reconstructed with a simple inside bracket. Results: Among 65 cases of combined liver-kidney transplantation, the success rate in the late 40 cases was 77.5%. The function of the grafted liver and kidney remained normal. Conclusion: This rat model of combined liver-kidney transplantation can be established in common laboratory conditions with high success rate and meet the needs of renal transplantation experiment.  相似文献   

13.
Objective To observe blood pressure change with age in salt-sensitive teenagers whose salt sensitivity were determined by repeated testing.Methods Salt sensitivity was determined through intravenous infusion of normal saline combined with volume-depletion by oral diuretic furosemide in 55 teenagers. After five years, salt sensitivity was re-examined and subject blood pressure was followed up. Blood pressure changes in salt-sensitive teenagers were compared to that of non-salt sensitive teenagers over five years.Results After 5 years, the repetition rate of salt sensitivity determined by intravenous saline loading is 92.7%. In teenagers with salt sensitivity on the baseline, both the systolic blood pressure increments and increment rates were much higher than non-salt sensitive teenagers (12.7±12.1 mmHg vs. 2.8±5.2 mmHg, P< 0.01; 12.2%± 12.0% vs. 2.5% ±4.4%, P< 0.001,respectively). There was a similar trend for diastolic blood pressure (8.4 ± 6.4 mmHg vs. 3.7 ± 6.4 mmHg, P = 0.052; 13.2% ±10.6 % vs. 6.8%± 10.1%, P = 0.053, respectively).Conclusions Salt sensitivity determined by intravenous saline loading showed good reproducibility. Blood pressure increments with age were much higher in salt-sensitive teenagers than non-salt sensitive teenagers, especially in terms of systolic blood pressure.  相似文献   

14.
Shock wave lithotripsy (SWL) is a treatment of choice for upper urinary stones. However, this procedure is inappropriate for obese patients because the focus is often unable to reach the target owing to the limited focal distance in shock wave source. Although treating such patients in a blast path may increase the application length of shock wave source, it's difficult to find this path on the lithotripter monitor. For this reason, we invented an adjustable calibration marker in order to set an effective focus in the shock wave hath.  相似文献   

15.
Excess production of reactive oxygen species(ROS)of mitochondrion mediated by hyperglycemia is the common pathogenesis of angiopathic complications of diabetes.TCM holds that the damp from the dysfunction of spleen.kidney and liver is the causative factor of complications of diabetes.This is similar to the mechanism of Ros resulting in angiopathic complications of diabetes.When the angiopathic complications of type II diabetes mellitus(T2DM)are difierentiated as caused by turbid damp in TCM can be explained as ROS.Since the obstruction of pathogenic damp in channels and collaterals is said to be the main pathogenesis,the treating principle should be dissolving the damp to remove the obstruction.  相似文献   

16.
INTRODUCTION Obesity is a complex emergent problem, which can be possibly solved not only by the diet but also by the life style and promotion of a constant physical exercise. 1, 2 No doubt careful attentions must be given to the nutritional condition of obese people, the dietary habits, the somatic build (i.e. distribution of fat mass) and the organic functions linked to formation of the fat mass. All the parameters should be constantly monitored before, during and after a diet treatment. 3, 4, 5  相似文献   

17.
People with dysglycemia are at high risk for atherosclerotic diseases. This study aims at investigating the atherosclerotic vascular damage in dysglycemia and its metabolic origin in Tibetan population.  相似文献   

18.
FOR anesthesiologis s ,treatingpostoperativepainhas alwaysbeen a problem.Althoughopioidshave been provedtobe effective,theirsideeffectscouldnotbeignored.With thedevelopmentofscienceand pharmacology,many drugs with aspectsof satisfactoryanalgesicefficacyand couldbe welltoleratedby patientshave been developed.And lornoxicamisone of them, which isa non-steroidalanti-inflammatorydrug (NSAID ), with analgesic, anti-infl-ammatory,andantipyreticproperties.Itseliminationhalf-time(3 to 5 hours) isle…  相似文献   

19.
目的:评价使用安心颗粒对急诊经皮冠状动脉介入术(PPCI)术后生活质量的影响.方法:将160例接受PPCI的急性ST段抬高型心肌梗死患者随机分为安心颗粒组(术前顿服安心颗粒8.8g,术后安心颗粒4.4 g/次,每日2次)和对照组(仅接受基础药物治疗).所有患者均服用阿司匹林、氯吡格雷和阿托伐他汀.分别在入院时、出院前1d、出院后180 d时,应用心肌梗死多维度量表(MIDAS)、中文版SF-36评价量表对患者生活质量评分.并观察术后30 d以内的出血并发症、血小板减少症发生情况.结果:入院时和出院前1d,两组患者的心肌梗死MIDAS、SF-36量表评分比较无差异(P>0.05);出院后180 d时,与对照组比较,安心颗粒组MIDAS、SF-36评分明显减低(P<0.05);组内与入院时比较,两组出院前1d、出院后180 d时,MIDAS、SF-36评分均降低(P<0.05).两组患者在随访期间均无大量出血、少量出血、重度和极重度血小板减少症发生,安心颗粒组有4例、对照组有7例发生不明显出血(P>0.05).两组发生轻度血小板减少症的患者数比较无差异(P>0.05).结论:PPCI使用安心颗粒,能改善急性ST段抬高型心肌梗死患者的生活质量,且不增加出血风险.  相似文献   

20.
Objectives To explore serum cytokines levels (including IL-1 β, sIL-2R, IL-6, TNF-α, and IFN-v) and their significance in patients with acute coronary syndrome (ACS) and the subsequent follow-ups, with attempt to estimate the role of various serum inflammatory markers in the diagnosis and assessment of ACS.Methods The study population include 40 patients with acute myocardial infarction (AMI), 40 patients with unstable angina pectoris (UAP), and 40 controls. Among the 80 patients, 60 patients attended a follow up 4 months later. Serum inflammatory markers including IL-1 β, sIL-2R, IL-6, TNF-α, and IFN-v were measured by enzyme linked immunosorbent assay.Results Serum IL- 1 β, sIL-2R, IL-6, TNF-α were significantly higher in AMI group or UAP group compared to the control group and became significantly lower 4 months later in the follow-up patients. Serum levels of IFN-v shows no significant difference between AMI group or UAP group and controls, also showing no significant change when measured in follow up patients. There was no correlation between serum creatine kinase-MB isoenzyme levels and serum inflammatory markers either in UAP or AMI group. Furthermore, when divided into two subgroups using Wagner's QRS scoring system in the AMI group, there is no difference of each serum inflammatory marker between ≤ 6 scores group and > 6 scores group.Conclusion Serum levels of certain inflammatory markers may have some diagnostic value for ACS, and can be a useful marker reflecting disease stability.  相似文献   

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