药物洗脱球囊在冠脉介入治疗后支架内再狭窄病变中的应用进展

经皮冠状动脉介入治疗(PCI)技术日趋成熟,已经在很大程度上提高了冠心病患者的生存率及生存质量。近10余年来,随着药物洗脱支架(DES)的普遍应用,介入治疗进入了新的阶段。然而,支架内再狭窄(ISR)的处理仍然是治疗的难点。药物洗脱球囊(DEB)能够将抗增生药物输送至靶病变部位,同时由于避免植入支架,减少了植入物刺激血管壁引起的炎症反应及内膜过度增生,从而降低了再狭窄率。因此,DEB在ISR等特殊病变治疗中具有特殊的优势。     

Treatment of coronary artery in-stent restenosis

Introduction: Although drug-eluting stents (DES) have significantly reduced the incidence and prevalence of coronary in-stent restenosis (ISR), ISR still occurs in approximately 10% of patients in real-world practice.

Areas covered: The development of newer generations of DES, drug-coated balloons (DCB) and increased use of intracoronary imaging have improved our treatment options for and pathophysiologic understanding of ISR. These technological advancements have also largely supplanted older modalities for treatment of ISR, such as brachytherapy, bare metal stents, conventional and cutting balloon angioplasty, and atherectomy devices. This article reviews the presentation, pathophysiology, and treatment of coronary artery ISR, with a focus on recent clinical data and emerging therapies for this difficult to treat clinical problem.

Expert commentary: DCB and second-generation DES are the most effective treatment options for ISR. Most trials support a slight superiority of second-generation DES, while DCB have the advantage of not adding another metal layer. The role of bioresorbable vascular scaffolds will be determined in the near future.     

药物涂层球囊在冠状动脉支架再狭窄介入治疗中的应用价值

目的 探讨冠状动脉支架内再狭窄患者中运用药物涂层球囊(DCB)处理的有效性及安全性.方法 对60例经冠脉造影证实冠状动脉内支架再狭窄患者,36例予以药物涂层球囊治疗,24例予以药物洗脱支架(DES)治疗,随访6个月并复查冠脉造影进行对比.结果 两组患者基线资料上差异无统计学意义(P>0.05);两组患者术后即刻药物洗脱...     

Drug-coated balloon angioplasty for drug-eluting stent restenosis: Insight from randomized controlled trials

Abstract

Background. The best treatment option for drug-eluting stent (DES) restenosis has not been established. We performed a meta-analysis to assess the clinical efficacy of drug-coated balloon (DCB) for the treatment of DES restenosis.

Methods. Trials were identified through a literature search from January 2005 through April 2014. All randomized controlled trials were eligible for inclusion if they compared DCB with a control treatment (plain old balloon angioplasty [POBA] or DES) in patients with DES restenosis.

Results. Five studies and a total of 864 patients were included in this analysis. Most end-points were significantly reduced for DCB compared with the control groups. For major adverse cardiac events, the relative risk (RR) was 0.49 (P = 0.012); for target lesion revascularization, it was 0.50 (P = 0.044); for recurrent restenosis, it was 0.41 (P = 0.002). There was a lower mortality for DCB (RR 0.29; P = 0.017). The incidence of myocardial infarction was numerically lower, but without statistical significance (RR 0.76; P = 0.55). The DCB effect was more pronounced when compared with POBA than when compared with DES.

Conclusions. This meta-analysis showed that DCB was superior to POBA and comparable to DES for treatment of DES restenosis. The findings in this meta-analysis cannot be extrapolated to DCB in general, because all DCB used in trials included was a single brand of paclitaxel-coated balloon.     

经皮冠状动脉介入术后支架再狭窄因素临床评价

目的:分析冠心病患者经皮冠状动脉介入术后支架内再狭窄的影响因素,并探讨其规律。方法:回顾性分析本院行冠状动脉介入治疗术后再次行冠状动脉造影的167例患者临床资料,分析急性心肌梗死组和非心肌梗死组、有症状组和无症状组冠状动脉支架再狭窄的发生率。结果:急性心肌梗死组患者支架术后支架再狭窄率高于非心肌梗死组患者(P<0.05);合并糖尿病患者再狭窄率高于未合并糖尿病患者(P<0.05);术后有可疑心绞痛症状者支架内再狭窄率高于无症状定期随访者(P<0.05)。结论:(1)急性心肌梗死、糖尿病可能由于其本身的病变特征,易致冠状动脉介入治疗术后支架内再狭窄。(2)根据临床症状可以初步诊断支架内再狭窄。     

药物球囊治疗冠状动脉支架内再狭窄的临床疗效

目的探讨药物球囊治疗冠状动脉支架内再狭窄后病变血管内膜腔的变化。 方法选取2016年5月至2017年12月确诊的不稳定型心绞痛患者,其在东南大学医学院附属江阴医院曾接受经皮冠状动脉药物洗脱支架植入术,因心绞痛再次接受冠状动脉造影检查,确定为支架内再狭窄的患者96例作为研究对象,将患者分为药物球囊治疗组（47例）及支架植入组（49例）,比较术后即刻最小内膜腔面积、支架最小截面积、支架膨胀率等,术后12个月复查冠状动脉造影及血管内超声检查,比较两组心血管事件、最小内膜腔面积、支架最小截面积、内膜增生面积等。 结果经冠状动脉造影及血管内超声检查：药物球囊治组疗术后即刻靶病变最小内膜腔面积和支架最小截面积均小于支架植入组［（10.8±2.8）mm² vs （11.8±3.2）mm²;（11.2±2.9）mm² vs （12.0±3.2）mm²］,差异具有统计学意义（t=2.112、1.987,P=0.025、0.042）;支架相对膨胀率药物球囊治疗组低于支架组（86.7% vs 90.3%）,差异具有统计学意义（χ²=2.012,P=0.045）。术后随访12个月,药物球囊治疗组发生心血管事件7例,支架植入组心血管事件9例,2组差异无统计学意义（P=0.699）;药物球囊治疗组与支架植入组支架植入处最小内膜腔面积［（10.6±2.6）mm² vs （10.8±2.7）mm²］比较,差异无统计学意义（P=0.896）;2组患者支架植入处内膜均有增生,但药物球囊治疗组与支架植入组内膜增生面积［（0.30±0.12）mm² vs （0.39±0.15）mm²］比较,差异无统计学意义（P=0.845）;药物球囊治疗组与支架植入组支架最小截面积［（10.9±2.7）mm² vs （11.2±3.0）mm²］比较,差异无统计学意义（P=0.723）。 结论药物球囊治疗支架内再狭窄后12个月其靶病变血管最小内膜腔面积、支架最小截面积、内膜增生面积与支架植入组相当,临床应用安全可靠。     

冠心病PCI术后再狭窄患者IL-18基因多态性的研究

目的研究白细胞介素-18（IL-18）基因多态性对冠心病患者经皮冠状动脉介入术（PCI）术后支架内再狭窄（ISR）易感性的潜在影响。方法将PCI术后的241例有再发缺血临床症状的冠心病患者作为研究对象,并根据冠状动脉造影结果分为支架内再狭窄（ISR）组（ISR组,n=68）和非ISR组（n=173）,另选择109例排除冠心病的人群作为对照组。采用聚合酶链反应对IL-18基因型进行检测,同时测定血清IL-18浓度。结果 ISR组、非ISR组患者G等位基因频率分别为0.93、0.83,二者明显高于对照组（0.73,P〈0.01）,ISR组患者的G等位基因频率明显高非ISR组（P〈0.01）。ISR组、非ISR组患者GG基因型频率分别为0.87、0.69,二者明显高于对照组（0.54,P〈0.01）,ISR组患者GG基因型频率明显高非ISR组（P〈0.01）。ISR组、非ISR组患者血清IL-18浓度分别为（309.39±86.75）、（245.37±59.04）ng/L,明显高于对照组[（138.41±47.28）ng/L]（P〈0.01）,ISR组患者血清IL-18浓度明显高于非ISR组（P〈0.01）。结论 IL-18启动子-137G/C基因多态性可能会影响血清IL-18浓度及PCI术后再狭窄发生的易感性。     

Comparison of two different paclitaxel-coated balloon catheters in the porcine coronary restenosis model

Background

Drug-eluting balloon (DEB) catheters coated with paclitaxel in a water-soluble matrix have shown beneficial effects in the treatment and prevention of restenosis in the porcine coronary overstretch model and in clinical trials. Adherence of paclitaxel, same dose, on another recently introduced coated percutaneous coronary intervention (PCI) catheter (DIOR^®) is mediated by a roughened balloon surface. Only scarce experimental and clinical data has been published on the new coating method. The aim of the present study was to compare the safety and efficacy of the two coatings in the porcine model.

Methods and results

Twenty-eight stainless steel stents were implanted in the left anterior descending and circumflex coronary arteries of 14 domestic pigs using either matrix-coated (n = 8), roughened DEB (n = 9), or uncoated PCI catheters, which served as control (n = 11). After 28 days, quantitative angiography and histomorphometry of the stented arteries were performed. Matrix-coated DEB led to a highly significant (P < 0.01) reduction of all parameters indicating neointimal proliferation compared to both, uncoated control and the roughened DEB; late lumen loss in-segment was 0.4 ± 0.2, 1.9 ± 0.5, and 1.4 ± 0.5 mm, respectively. In contrast, the roughened DEB failed to produce statistically significant effects on angiographic measures of stenosis or morphometric parameters such as maximal neointimal thickness and luminal area, except for neointimal area (5.7 ± 1.5 mm² in the control group, 4.1 ± 1.7 mm² roughened DEB, P < 0.05 vs. control, and 2.5 ± 0.8 mm² matrix-coated DEB, P < 0.01 vs. control).

Conclusion

Inhibition of neointimal proliferation in the porcine coronary overstretch model by paclitaxel depends critically on the coating method.

     

The endovascular approach for in-stent restenosis in femoropopliteal disease

In-stent restenosis remains one of the main drawbacks of stenting the femoropopliteal segment, and leads to stent failure and repeated interventions. A variety of endovascular techniques have been investigated so far to reduce this phenomenon, including plain angioplasty, atherectomy, new stent deployment, cutting balloons and cryoplasty but without satisfactory mid- and long-term results. More recently drug-eluting devices have been applied in femoropopliteal in-stent restenosis with promising results. The aim of this review is to analyse the indication and effectiveness of those endovascular techniques for the treatment of in-stent restenosis.     

Treatment of small coronary arteries with a paclitaxel-coated balloon catheter

Background

Treatment of lesions in small coronary arteries by percutaneous transluminal coronary intervention is limited by a high recurrence rate. We assessed the use of a paclitaxel-coated balloon in this indication.

Methods

One-hundred eighteen patients with stenoses in small coronary vessels were treated by a paclitaxel-coated balloon (3 μg/mm²). The main inclusion criteria encompassed diameter stenosis of ≥70% and ≤22 mm in length with a vessel diameter of 2.25–2.8 mm. Follow-up angiography was performed at scheduled 6-month post-intervention or whenever driven by clinical or electrocardiographic signs of ischemia. The primary endpoint was angiographic in-segment late lumen loss.

Results

Eighty-two of 118 patients (70%) with a vessel diameter of 2.35 ± 0.19 mm were treated with the drug-coated balloon only, while 32 patients required additional stent deployment. The mean in-segment late lumen loss was 0.28 ± 0.53 mm. In patients treated with the drug-coated balloon only, the in-segment late lumen loss was 0.16 ± 0.38 mm. At 12 months, the rate of major adverse cardiac events was 15% which was primarily due to the need for target lesion revascularization in 14 patients (12%). In those with additional bare metal stent implantation geographical mismatch between coated-balloon dilatation and stent implantation was significantly associated with the occurrence of restenosis.

Conclusion

Treatment of coronary stenosis in small coronary vessels with the paclitaxel-coated balloon was well tolerated. It may offer an alternative to the implantation of a drug-eluting stent (ClinicalTrials.gov Identifier: NCT00404144).     

兔颈总动脉损伤后普罗布考对血管再狭窄的抑制作用

目的 研究普罗布考减轻动脉成形术后再狭窄的作用.方法 将30只新西兰大白兔随机分为普罗布考治疗组和对照组各15只.以球囊损伤颈总动脉,用高胆固醇食物饲养8周后切取颈总动脉,HE染色观察血管管腔面积和内膜面积的变化.采用明胶酶谱法和酶法测定动物血清中基质金属蛋白酶2的酶原(pro-MMP-2)、基质金属蛋白酶2(MMP-2)及血清胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)的水平.结果 普罗布考组TC、LDL-C、TG和HDDC水平较对照组低,但差异无显著性(P＞0.05);普罗布考组pro-MP-2、MMP-2水平较对照组低,两组比较均具有显著性差异(P＜0.05);普罗布考组颈总动脉新生内膜面积、最大内膜厚度明显低于对照组,两者比较差异具有显著性(P＜0.05);而普罗布考组颈总动脉管腔面积明显高于对照组后,两者比较差异具有显著性(P＜0.05).结论 普罗布考可通过抑制MMPs的途径减轻兔颈总动脉成形术后再狭窄的形成.     

Cost-effectiveness of paclitaxel-coated balloon angioplasty and paclitaxel-eluting stent implantation for treatment of coronary in-stent restenosis in patients with stable coronary artery disease

Background  

Recent studies have demonstrated the safety and efficacy of drug-coated balloon (DCB) angioplasty for the treatment of coronary in-stent restenosis (ISR). The cost-effectiveness of this practice is unknown.     

Treatment of in-stent restenosis with sirolimus-eluting-stents: results from the prospective German Cypher stent registry

Aims  Drug-eluting stents have been reported to effectively reduce in-stent restenosis (ISR). However, the effectiveness and safety have yet been investigated only in small trials or case series. The aim of this prospective large scale registry was to show that treatment of ISR with sirolimus eluting stents (SES) is safe, effective and feasible in daily routine. Methods and results  The German Cypher registry prospectively enrolled 6,555 patients undergoing implantation with SES for various indications, including 1,533 patients treated for ISR. Follow-up data (median 6.6 months) of this cohort was available for 1,531 patients (99.8%). Of these patients 75.8% were male. Of these patients 36.5% (n = 552) presented with acute coronary syndromes. In total, 1,932 SES were used with successful implantation in 98.9%. MI during hospitalization was observed in 0.7% (n = 11) while in-hospital mortality was only 0.1% (n = 2). MACE-rate at follow-up was 13.8% (n = 211) including a mortality of 1.3% (n = 20) and MI in 1.9% (n = 29). Total revascularization procedures including CABG (1.7%) were necessary in 12.3% (n = 186). Target vessel revascularization (TVR) rate was 9.3% (n = 139) and thus similar to patients with de novo lesions (8.1%, P = 0.69). Ten patients (0.65%) suffered from subacute stent thrombosis Vs. 0.24% observed in patients with de novo lesions (P = 0.03). Conclusion  This large registry confirms that treatment of ISR with sirolimus-eluting-stents is effective and save with good clinical results at index procedure and follow-up. TVR was not different from de novo lesions.     

不同造影分型对大脑中动脉支架内再狭窄的影响

目的 比较不同造影分型对大脑中动脉支架内再狭窄(ISR)的影响.方法 选择行大脑中动脉支架置入术的患者116例作为研究对象,按照部位-形态学-路径分型(LMA分型)进行造影分型(部位分型分为7个亚型,形态学分型分为3个亚型,路径分型分为3个亚型),随访患者再狭窄发生情况,并分析大脑中动脉ISR的LMA分型影响因素.结果...     

血清ECP水平与药物洗脱支架晚期支架内再狭窄的相关性

目的:探讨嗜酸性粒细胞阳离子蛋白(eosinophil cationic protein, ECP)与药物洗脱支架(drug eluting stent, DES)晚期支架内再狭窄(in-stent restenosis, ISR)的相关性。方法:选取2014年12月至2016年7月在复旦大学附属中山医院植入DES并超过1年后返院复查造影患者202例,根据复查造影结果分为ISR组(100例)和无ISR组(102例),应用夹心酶联免疫吸附(ELISA)法测定血清ECP水平并比较其在2组间差异。在ISR组和无ISR组,根据支架载药涂层,进一步分为永久涂层-DES组(DP-DES亚组)及可降解涂层-DES组(BP-DES亚组),分析血清ECP水平与载药涂层的关系。结果:ISR组血清ECP水平明显高于无ISR组(P=0.003)。手术年龄和ECP水平是晚期ISR形成的独立危险因素。ISR组DP-DES亚组血清ECP水平高于无ISR组DP-DES亚组(P=0.002)。结论:血清ECP水平在晚期ISR患者中显著升高,可能与支架药物涂层有关。     

血清Hcy、sCD40L及LDL-C与冠状动脉支架内再狭窄的相关性研究

目的:探讨血清同型半胱氨酸(Hcy)、LDL-C、可溶性白细胞表面抗原40配体(sCD40L)等因素在冠状动脉支架内再狭窄发生过程中的临床意义。方法:收集冠状动脉药物涂层支架植入术后因胸痛再发/术后6个月常规行冠状动脉造影随访患者共120例,其中88例造影未出现支架内再狭窄(对照组),32例出现再狭窄(再狭窄组),回顾分析两组患者的年龄、性别、高血压病史、糖尿病史、心肌梗死病史及冠心病家族史,收集患者支架植入术后1周以及胸痛再发/术后6个月冠状动脉造影检查这两个时间点的BMI、肾小球滤过率(GFP)、甘油三酯、总胆固醇、糖化血红蛋白(GHbA1c)、LDL-C、HDL-C、Hcy、sCD40L等指标。结果:两组患者在支架植入术后1周各指标比较差异无统计学意义,因胸痛再发/术后6个月行冠状动脉造影随访时发现再狭窄组的LDL-C、Hcy、sCD40L和对照组比较差异有统计学意义(P<0.01),二分类变量Logistic回归分析显示,LDL-C、sCD40L及Hcy的升高会增加再狭窄的风险,且Hcy与LDL-C(r=0.36,P=0.002)、sCD40L(r=0.27,P=0.001)呈正相关。结论:支架植入术后LDL-C、Hcy、sCD40L升高是支架内再狭窄的危险因子,并且Hcy与LDL-C、sCD40L呈正相关。     

多层螺旋CT对冠状动脉支架再狭窄的半定量评估

目的：评价多层螺旋CT血管造影对冠状动脉支架术后再狭窄评估的临床价值。材料与方法：通过对34例65个冠状动脉支架植入术后的病例进行64排螺旋CT增强扫描和导管冠状动脉造影，评估冠状动脉支架内再狭窄。结果：本组病例多层螺旋CT检查冠状动脉支架内再狭窄的敏感度为82．4％、特异度为97．9％、假阳性率为2．1％、假阴性率为17．6％、符合率为93．8％、阳性预测值为93.3％、阴性预测值为94．0％。结论：多层螺旋CT在冠状动脉介入术后冠状动脉支架再狭窄的显示有较高的临床价值，并可作出半定量评估。     

药物洗脱支架内再狭窄的危险因素分析

目的 探讨冠状动脉药物洗脱支架内再狭窄的危险因素.方法 对157例行冠状动脉药物洗脱支架植入术患者的临床资料进行回顾性分析,按照冠状动脉造影结果分为再狭窄组33例和无再狭窄组124例,采用单因素及Logistic多因素回归分析其临床及冠状动脉造影特征与药物洗脱支架内再狭窄的相关性.结果 再狭窄组33例,糖尿病18例(54.5%),术后反复心绞痛26例(78.8%);无再狭窄组124例,糖尿病31例(25.0%),术后反复心绞痛72例(58.1%),组间差异有统计学意义(χ2=10.60,P＜0.01;χ2=4.77,P=0.03).2组慢性完全闭塞分别为11例(19.3%)、12例(7.6%),分叉病变12例(21.1%)、16例(10.2%),弥漫病变15例(26.3%)、19例(12.1%),组间差异有统计学意义(χ2值分别为5.92、4.34、6.32,P均＜0.05).再狭窄组植入支架57枚,无再狭窄组植入157枚.Logistic多因素分析显示糖尿病、术后反复心绞痛、慢性完全闭塞、分叉病变、弥漫病变和支架长度与支架内再狭窄相关(OR分别为3.52、2.59、3.05、3.14、3.08、0.93,95%CI分别为1.56～7.90,1.02～6.59,1.11～8.36,1.30～7.59,1.34～7.05,0.88～0.98,P均＜0.05).结论 冠状动脉药物洗脱支架植入术后,糖尿病史、术后反复发生心绞痛、慢性完全闭塞、分叉病变、弥漫病变及支架长度为支架内再狭窄的危险因素.

Abstract：

Objective To investigate the risk factors of in-stent restenosis (ISR) after coronary implantation of drug-eluting stent Methods One hundred and fifty-seven patients including 118 males and 39 females,who underwent successful implantation of drug-eluting stent, were recruited in the study. The patients were divided into the restenosis group (33 patients) and non-restenosis group ( 124 patients) according to the angiographic results. The associations of ISR with clinical and coronary angiographic characteristics were analyzed using univiriate analysis and logistic regression. Results In the restenosis group,there were 18 cases of diabetes mellitus ( 54. 5% ), 26 cases of frequency angina ( 78. 8% ), which were significantly higher than those of 31 cases of diabetes (25.0%) and 72 case of frequent angina (58. 1% ) in the non-restenosis group (χ2 = 10. 60, P ＜ 0. 01, χ2 = 4. 77, P = 0. 03 for diabetes mellitus and frequent angina, respectively). Compared to non-restenosis group, the occurrence rates of chronic total occasion, bifurcatus lesions, diffuse lesions were significandy higher in the restenosis group ( 19. 3% vs 7. 6% χ2 =5.92,21.1% vs 10. 2% χ2 =4. 34,26. 3%vs 12. 1% χ2 =6. 32,Ps ＜0. 05). Fifty-seven stents were implanted into the restenosis group,and one hundred and fifty-seven into the non-restenosis group. Logistic regression analysis showed that diabetes, frequent angina,chronic total occlusion lesions, bifurcatus lesions, diffuse lesions, stent length and diameter were significantly associated with restenosis ( OR value were 3.52,2. 59,3.05,3. 14,3.08,0. 93,95% CI were 1.56 - 7.90,1.02 - 6. 59,1.11 - 8. 36,1.30 - 7.59,1.34 - 7.05,0. 88 - 0. 98 respectively, Ps ＜ 0. 05 ). Conclusion After implantation of drug-eluting stent, diabetes mellitus, chronic total occasion lesions, frequent angina, diffuse lesions, bifurcatus lesions and stent length and diameter are associated with follow-up restenosis.     

紫杉醇药涂球囊在治疗症状性下肢动脉硬化闭塞症的临床随访研究

目的探讨紫杉醇药涂球囊在治疗症状性下肢动脉硬化闭塞症的临床效果.方法选取2016年1月至2017年4月上海交通大学医学院附属新华医院(崇明分院)收治的股腘动脉狭窄的症状性下肢动脉硬化闭塞症患者64例作为研究对象.按照随机原则分为两组,每组32例.药涂组先予普通球囊预扩张,然后采取紫杉醇药物涂层球囊扩张,若仍有病变血管回缩、狭窄,影响下肢血流,则植入补救性支架;裸支架组采取稍小球囊预扩股浅动脉血管后释放支架.术后随访1年,观察两组患者治疗前及治疗后6、12个月踝臂指数(ankle-brachialindex,ABI)变化、靶病变血管再狭窄率、Rutherford分级变化、临床驱动靶血管血运重建率,以及围手术期、随访期间患者死亡比例、截肢率以及并发症发生率等.结果全组围手术期及随访期间无截肢及死亡患者,药涂组并发症发生率为 3.1%(1/32),显著低于裸支架组的18.8%(6/32)(χ^2=4.010,P=0.045).治疗前,治疗后6、12个月药涂组和裸支架组患者的ABI比较差异有统计学意义(F组间=7.028,P组间=0.024;F组内=219.028, P组内=0.000;F交互=350.028,P交互=0.000),且两组治疗后12个月ABI分别为(0.73±0.11)和(0.68±0.09),差异有统计学意义(t=1.990,P=0.025).两组患者术后6个月靶病变血管再狭窄率分别为9.4%(3/32)和15.6%(5/32),差异无统计学意义(χ^2=0.571,P=0.450);术后12个月裸支架组再狭窄率为37.5%(12/32),显著高于药涂组15.6%(5/32)(χ^2=3.925,P=0.048).临床观察结果显示,术后 12 个月,药涂组临床驱动靶血管血运重建率(target-lesionrevascularization, TLR)为 3.1%(1/32),裸支架组为9.4%(3/32),差异无统计学意义(χ^2=1.067,P>0.05).两组患者Rutherford分级均较术前得到改善.结论紫杉醇药涂球囊治疗症状性下肢动脉硬化闭塞症安全、有效,值得在临床上推广应用.