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目的 利用大脑中动脉梗塞(middle cerebral artery occlusion,MCAO)大鼠模型,观察脑缺血再灌注后脑组织低氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)表达的动态变化,并给予脑缺血大鼠锌离子螯合剂[N,N,N’,N ’-tetrakis(2-pyridylmethyl)ethylenediamine,TPEN]进行干预,研究锌离子对MCAO大鼠脑组织HIF-1α表达的影响,探讨锌离子介导脑缺血再灌注损伤的相关机制。方法 采用数字表法将45只健康雄性Sprague-Dawley大鼠随机分为3组:假手术组(Sham)、MCAO组和MCAO+TPEN组(于MCAO前30 min腹腔注射TPEN,剂量为15 mg/kg),每组15只。使用线栓法制作大鼠右侧大脑中动脉缺血90 min再灌注模型。术中监测大鼠肛温及平均动脉压,使其维持在正常范围。分别于再灌注3、12和24 h处死大鼠,迅速取脑,用免疫组化染色检测大鼠脑组织冰冻切片内缺血半暗带区HIF-1α的表达水平,用免疫荧光双标对HIF-1α在缺血脑组织的表达进行细胞定位。结果 假手术组大鼠未见HIF-1α染色阳性细胞,MCAO组大鼠脑组织缺血半暗带区HIF-1α的表达随再灌注时间延长逐渐增加(P<0.01)。给予15 mg/kg TPEN后,缺血再灌注各时间点大鼠脑组织缺血半暗带区内HIF-1α的表达比MCAO组明显减少(P<0.01)。缺血再灌注大鼠脑组织缺血半暗带区内,HIF-1α免疫荧光染色与神经元标志物NeuN免疫荧光染色共定位。结论 大鼠局灶性脑缺血再灌注后,脑组织神经元内HIF-1α表达随再灌注时间延长递增。螯合细胞内锌离子下调缺血再灌注大鼠脑内HIF-1α浓度,提示锌离子可能通过促进HIF-1α表达介导脑缺血损伤。  相似文献   

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目的 研究大黄酚(chrysophanol,CHR)对短暂性局灶性脑缺血再灌注小鼠缺血半暗带区自噬蛋白Beclin1及缺血侧大脑半球促凋亡蛋白Bax水平的影响,探究CHR对脑缺血再灌注损伤的保护机制。方法 将18只健康C57BL/B6雄性小鼠按数字表法随机分为3组:假手术(Sham)组、大脑中动脉梗死(middle cerebral artery occlusion,MCAO)组、CHR组(自造模当天至再灌注后14 d每天按0.1 mg/kg腹腔注射CHR),每组6只。按照线栓法制作小鼠右侧大脑中动脉缺血45 min再灌注模型。再灌注14 d时将小鼠处死后,迅速断头、取脑,应用免疫荧光染色法检测脑组织冰冻切片缺血半暗带区自噬Beclin1水平,Western blotting法检测缺血侧脑组织Bax蛋白水平。结果 1) Sham组小鼠脑内偶见Beclin1阳性细胞。MCAO组小鼠脑缺血半暗带区Beclin1表达水平比Sham组显著升高(P<0.05)。给予CHR治疗的脑缺血再灌注小鼠半暗带区Beclin1的表达水平比MCAO组显著减少(P<0.05)。2)在脑缺血半暗带区,Beclin1与神经元标志物NeuN共定位。3) MCAO组小鼠缺血侧脑组织Bax蛋白水平比Sham组明显升高(P<0.05)。CHR组小鼠缺血侧脑组织Bax蛋白水平比MCAO组显著减少(P<0.05)。结论 CHR可能通过抑制Bax蛋白表达水平,减少Beclin1蛋白产生,减轻神经元凋亡,避免自噬过度激活,从而对脑缺血再灌注损伤发挥长期神经保护作用。  相似文献   

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目的 观察一氧化氮(nitric oxide,NO)清除剂Carboxy-PTIO (C-PTIO)对大脑中动脉梗死(middle cerebral artery occlusion,MCAO)模型大鼠再灌注后24 h脑组织中PERK/p-eIF2α通路介导的细胞死亡的影响,探究NO的产生对大鼠脑内内质网应激(endoplasmic reticulum stress,ERS)介导的神经元凋亡的影响。方法 将18只健康雄性SD大鼠依据数字表法随机分为假手术(Sham)组、MCAO组和MCAO+C-PTIO组,每组6只。大鼠大脑中动脉缺血再灌注模型制作采用改良线栓法,并于缺血90 min后拔出线栓进行再灌注。术中监测大鼠肛温,使其维持在正常范围。于再灌注后24 h处死大鼠,迅速取脑,用免疫荧光染色检测大鼠脑组织冰冻切片缺血半暗带区p-eIF2α和C/EBP homologous protein (CHOP)的表达水平,用免疫荧光双标法将NO介导的蛋白质损伤标志物3-硝基酪氨酸(3-nitrotyrosine,3-NT)分别与p-eIF2α和CHOP进行定位。结果 1) Sham组大鼠没有p-eIF2α和3-NT染色阳性细胞,偶见CHOP染色阳性细胞,MCAO组大鼠脑组织缺血半暗带区3-NT、p-eIF2α、CHOP均大量表达(P<0.05)。2)与MCAO组相比,经腹腔注射给予C-PTIO后,缺血再灌注大鼠脑组织半暗带区3-NT、p-eIF2α、CHOP表达均明显减少(P<0.05)。3)缺血再灌注大鼠脑组织半暗带区,3-NT分别与p-eIF2α和CHOP免疫荧光染色共定位。结论 在脑缺血再灌注过程中,NO介导的氧化应激损伤引起ERS,并激活PERK/eIF2α通路引起细胞凋亡;抑制NO的产生,可以减弱这一过程,起到神经保护作用。  相似文献   

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目的 研究山茱萸环烯醚萜苷(cornel iridoid glycoside,CIG)对大脑中动脉梗阻(middle cerebral artery occlusion,MCAO)模型大鼠大脑皮质线粒体损伤的作用,探讨CIG对脑缺血再灌注损伤的保护作用机制。方法 采用线栓法制备大鼠MCAO模型,缺血2 h后复灌,采用数字表法将大鼠随机分为5组:假手术组,模型组,CIG低、高剂量(60、120 mg/kg)给药组,阳性对照药银杏叶片组,于复灌6 h后开始灌胃给药,每日1次,连续给药7 d。采用神经功能缺损症状评分(Modified Neurological Severity Scores,mNSS)评价各组大鼠神经功能情况,透射电镜观察损伤侧皮质部位线粒体超微结构,Western blotting法检测线粒体功能相关的蛋白NIX、Beclin1、DRP1、OPA1和PGC-1α的表达。结果 脑缺血再灌注损伤7 d后,模型组大鼠mNSS评分较假手术组大鼠显著增高,而与模型组相比,各给药组大鼠的mNSS评分明显降低。透射电镜结果显示模型组大鼠皮质线粒体损伤严重,CIG给药能明显改善线粒体结构变化。Western blotting检测结果显示,缺血再灌注损伤可显著抑制大鼠皮质组织中NIX、Beclin1、DRP1、OPA1和PGC-1α蛋白的表达,而CIG给药后均能显著改善这些蛋白的异常表达。结论 CIG通过激活线粒体自噬,促进线粒体分裂融合,增加线粒体生物合成等过程,减轻线粒体损伤,进而保护神经元,发挥较好的抗脑缺血再灌注损伤的脑保护作用。  相似文献   

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目的 探究一氧化氮合酶(nitric oxide synthase,NOS)抑制剂N-硝基-L-精氨酸甲酯(Nω-nitro-L-arginine methyl ester,L-NAME)对大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)模型大鼠再灌注后24 h脑内一氧化氮(nitric oxide,NO)和自噬相关蛋白Beclin1、LC3B表达的影响,探讨L-NAME保护脑缺血再灌注损伤的机制。方法 18只健康雄性SD大鼠采用随机数字表法分为假手术(Sham)组、MCAO组,和MCAO+L-NAME组,每组6只。使用改良线栓法制作大鼠右侧大脑中动脉缺血90 min再灌注模型。术中监测大鼠肛温,使其维持在正常范围。于再灌注后24 h处死大鼠,迅速取脑,用免疫荧光染色检测小鼠脑组织冰冻切片缺血半暗带区Beclin1和LC3B的表达水平,用免疫荧光双标分别将Beclin1和LC3B与NO介导的蛋白质损伤标志物3-硝基酪氨酸(3-nitrotyrosine,3-NT)进行共定位。结果 Sham组大鼠没有3-NT染色阳性细胞,偶见Beclin1和LC3B染色阳性细胞,MCAO组小鼠脑组织缺血半暗带区3-NT、Beclin1、LC3B均大量表达(P<0.05)。与MCAO组相比,给予L-NAME治疗后,缺血再灌注大鼠脑组织半暗带区3-NT、Beclin1、LC3B表达均明显减少(P<0.05)。缺血再灌注小鼠脑组织半暗带区,Beclin1和LC3B分别与3-NT免疫荧光染色共定位。结论 L-NAME通过抑制NOS活性,减少NO的产生,直接避免神经元的氧化应激损伤;同时,氧化应激损伤的减弱也避免了自噬的进一步激活,起到了间接的神经保护作用。  相似文献   

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目的 探讨丁苯酞(NBP)对缺血再灌注大脑神经元和血脑屏障影响。方法 SD 大鼠 30 只随机分为假手术组、缺血 再灌注组、NBP 20 mg/kg 组、NBP 40 mg/kg 组、NBP 80 mg/kg 组,术前 1 周灌胃给不同剂量 NBP,共 7 d。线栓法制作大 脑中动脉缺血再灌注模型,术后进行神经行为学评分,检测大脑组织中伊文思蓝的含量和血脑屏障通透性变化,透射电 镜观察缺血区脑组织神经元和血脑屏障的超微结构变化。结果 与缺血再灌注组比较,NBP 各组神经功能缺损评分明显降 低(P<0.01,P<0.05),脑组织中伊文思蓝的含量减少(P<0.01,P<0.05),血脑屏障的通透性降低,神经元和血脑屏障 超微结构损伤明显减轻。结论 丁苯酞预处理对脑缺血再灌注损伤神经元和血脑屏障具有预防保护作用  相似文献   

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目的 观察中药益智胶囊对大鼠全脑缺血后海马CA1区神经元迟发性死亡及学习功能的影响。方法 以四血管闭塞(4-VO)法制成大鼠急性全脑缺血再灌注模型。采用免疫组织化学方法计数脑缺血再灌注脑损伤后1、2、4、8及40d后,大鼠海马CA1区正常神经元数目;用Morris水迷宫实验观察脑缺血再灌注脑损伤后40d时各组大鼠的学习记忆功能。结果 从缺血再灌注后第2天起,益智胶囊(100mg/kg·b.w.)组大鼠海马CA1区正常神经元数量显著高多于缺血对照组大鼠(P<0.01)。全脑缺血再灌注脑损伤后40d时,益智胶囊(100mg/kg·b.w.)组大鼠记忆功能明显好于缺血对照组大鼠(P<0.01)。结论 益智胶囊对全脑缺血后大鼠海马CA1区神经元具有保护作用,并可改善大鼠的记忆功能障碍。  相似文献   

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目的 观察腺苷预处理(AP)对脑缺血再灌注损伤大鼠脑组织中CCAAT/增强子结合蛋白同源蛋白(CHOP)表达的影响,探讨AP对脑缺血再灌注损伤大鼠的神经保护作用机制。方法 将36只健康雄性Sprague Dawley大鼠按随机数字表法分为假手术组、缺血再灌注(IR)组和AP组,每组12只。AP组大鼠术前3 d腹腔注射1.5 mg·kg-1腺苷注射液,每日1次;假手术组和IR组大鼠术前3 d腹腔注射等量生理盐水,每日1次。IR组及AP组大鼠采用线栓法制备大脑中动脉栓塞(MCAO)模型,并于栓塞2 h后拔出栓线恢复血供制备IR模型;假手术组大鼠不插入栓线,余处理同IR组及AP组。于再灌注24 h时,根据5分制神经行为学评分标准对3组大鼠进行神经功能缺损评分;然后,断头处死3组大鼠,取脑组织;应用苏木精-伊红染色法观察3组大鼠脑组织病理学改变,实时荧光定量聚合酶链式反应法检测3组大鼠脑组织中CHOP mRNA相对表达量,免疫组织化学法检测3组大鼠脑组织中CHOP蛋白阳性表达情况,脱氧核糖核苷酸末端转移酶介导的缺口末端标记法检测3组大鼠脑组织细胞凋亡情况。结果 3组大鼠神经功能缺损评分比较差异有统计学意义(F=157.923,P<0.05);IR 组和AP组大鼠神经功能缺损评分显著高于假手术组(t=17.663、7.133,P<0.05),AP组大鼠神经功能缺损评分显著低于IR 组(t=-10.530,P<0.05)。假手术组大鼠脑组织神经元形态结构正常,细胞核完整,间质无水肿;IR组大鼠脑组织神经元数目减少、细胞核溶解、出现空泡,间质水肿,组织疏松;AP组大鼠神经元损伤程度显著低于IR组。3组大鼠脑组织中CHOP mRNA相对表达量比较差异有统计学意义(F=2 989.751,P<0.05);IR组和AP组大鼠脑组织中CHOP mRNA相对表达量显著高于假手术组 (t=75.514、23.502,P<0.05),AP组大鼠脑组织中CHOP mRNA相对表达量显著低于IR 组(t=-52.171,P<0.05)。3组大鼠脑组织中CHOP 蛋白阳性细胞表达率比较差异有统计学意义(F=2 257.096,P<0.05);IR组和AP组大鼠脑组织中CHOP 蛋白阳性细胞表达率显著高于假手术组(t=65.927、21.744,P<0.05),AP组大鼠脑组织中CHOP 蛋白阳性细胞表达率显著低于IR组(t=-44.183,P<0.05)。3组大鼠脑组织细胞凋亡率比较差异有统计学意义(F=1 519.372,P<0.05);IR组和AP组大鼠脑组织细胞凋亡率显著高于假手术组(t=5.512、2.693,P<0.05),AP组大鼠脑组织细胞凋亡率显著低于IR组(t=-2.818,P<0.05)。结论 AP可通过抑制CHOP的表达减轻脑缺血再灌注损伤。  相似文献   

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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   

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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   

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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   

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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   

15.
Objective:To investigate the influences of urapidil and nicardipine on rabbit sinus function,atrio-ventricular node function and hemodynamics.Methods:Thirty-two Angora's rabbits were selected and randomly divided into four groups.U1 group:urapidil 0.25 mg/kg;U2 group:urapidil 0.5 mg/kg;N1 group:nicardipine 10 μg/kg;N2 group:nicardipine 20 μg/kg.All these medicine were administrated within 30 seconds.Measurements were taken before and after the administration of urapidil or nicardipine for the following data:mean blood pressure(MAP),heart rate(HR),sino-atrial conduction time(SACT),maximal sinoatrial recovery time(SNRTmax)corrected sinus node recovery time(CSNRT),index of sinus node recovery time(SNRTI),Wenckebach A-V conduction frequency (WB),and P-R interval.Results:Significant MAP and HR changes were identified in all of the four groups before and after administration of both urapidil and nicardipine.No significant changes could be found in the rest of the parameters.Intergroup analysis showed that SACT and CSNRT of N1 and N2 groups were shorter than those of the U2 group(P<0.01);the MAP decreased(P<0.01)and the HR increased drastically(P<0.01).Conclusions:Neither urapidil(0.25 mg/kg,0.5 mg/kg)nor nicardipine(10μg/kg,20μg/kg)has any significant influence on rabbit sinus function or rabbit atrio-ventricular node function.Nicardipine could be a better choice than urapidil for parafunctional sinus node patients.  相似文献   

16.
Objective:To investigate the gene expression of osteoprotegerin(OPG) and osteoclast differentiation factor(ODF) in the bone tissue of patients with hip fracture due to osteoporosis. Methods:OPGmRNA and ODFmRNA in the bone tissue in 50 cases of osteoporosis sufferers(over 50 years old) with hip fracture(Observer Group) and 30 cases of hip facture sufferers with no osteoporosis(Control group) were analyzed with the Semi-Quantitative RT-PCR method. Results:The mRNA expressed of ODF, OPG were both high in the patients with hip fracture. In the control group, the expression of OPG mRNA was observed, while the expression of ODF mRNA was very slight. Conclusion:Aged patients contained all signals including OPG, ODF that are essential for inducing osteoclastogenesis and promoting bone resorption.  相似文献   

17.
Objective:To probe into the influence of changes of ovarian hormones on the pathogenesis of the specific sub-type premenstrual syndrome(PMS)and reveal partial microcosmic mechanisms of adverse flow of liver-qi.Methods:Estradiol(E2)and progesterone(P)levels in serum were determined at different phases of menstrual cycle by radioimmunoassay.Results:In the group of PMS with adverse flow of liver-qi.the secretive peak value Of E2 and P at the follicular phase significantly decreased,and the secretive peak value at the luteal phase did not come into being.Conclusions:Low E2 and P secretive peak at the follicular phase and absence of secretive peak at the luteal phase is one of the microcosmic mechanisms of PMS with adverse flow of liver-qi.One of the pathophysiologic mechanisms of specific sub-type PMS is probably the continuous low level of E2and P.  相似文献   

18.
Real-time three-dimensional echocardiography (RT3DE)is a new ultrasound technique that enables dynamic threedimensional visualization and quantification of the heart in real time. Investigation of feasibility and methodology of RT3DE in determining left ventricular (LV) and right ventricular (RV) volumes, RT3DE was performed in 35 normal adults using Philips SONOS 7500 system with a 2-4 MHz matrix array transducer. The 60°×60° "pyramid" volume database was obtained and analyzed on a TomTec echo workstation. Both LV and RV volumes were calculated with four 3DE methods (i.e. apical 2, 4, 8, and 16-plane) through manually tracing ventricular endocardial borders in end diastole and end systole. Stroke volumes were then calculated. LV volume was also measured by 2DE Simpson's rule using GE VIVID 7 ultrasound machine.  相似文献   

19.
Increasing maternal age is the only etiological factor unequivocally linked to Down's syndrome in humans. The occurrence rate of newborns with Down's syndrome is about 1/220 in women over 35 years old. However, the occurrence rate in embryos fertilized in vitro, of the elder woman is unclear. Using FISH we screened the number of chromosome 21 in preimplanted embryos of 5 elderly women (average age, 38.4 years) to study the feasibility and necessity of screening trisomy 21 in embryos in patients over 35 years old at the in vitro fertilization (IVF) center.  相似文献   

20.
A clinical guideline for the therapeutic interventions of integrative medicine may be defined as a written document which states a series of recommendations on therapeutic interventions of integrative medicine for a special disease or condition. The guideline may provide assistance to medical professionals in making clinical decisions aimed at improving the clinical outcome of patients and reducing the costs of medical care(~'4~. Recommendations issued by a guideline should be based on the best available evidence in both Western and Chinese medicine. For fulfilling this purpose, the development of clinical guidelines for therapeutic interventions in the field of integrative medicine should follow scientific principles and undergo a rigorous processes.  相似文献   

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