依贝沙坦对自发性高血压大鼠左心室肥厚和心肌纤维化的影响

目的探讨依贝沙坦对自发性高血压大鼠(SHR)左心室肥厚(LVH)和心肌纤维化的影响。方法18只16周龄SHR,随机分为依贝沙坦治疗组(SHR-I)和SHR空白对照组(SHR-C);另设同源的WKY大鼠8只为正常对照组。治疗组口服依贝沙坦50mg.kg-1.d-1给药8周后处死动物,取左心室心肌称重,计算左心室/体重比(LVW/BW),Masson三色法染色观察左心室心肌胶原变化,计算机图象分析测量心肌切片的胶原容积分数(CVF)和血管周围胶原面积(PVCA)。结果SHR空白对照组的收缩压(SBP),LVW/BW,CVF,PVCA均显著高于WKY对照组(P<0.01),与SHR空白对照组相比,依贝沙坦治疗组能有效降低SHR的SBP,改善左心室肥厚(P<0.01)并使左心室内膜及心肌小动脉周围的胶原减少(P<0.01)。结论依贝沙坦可有效降低SHR血压,部分逆转心肌纤维化和左心室肥厚。     

厄贝沙坦和咪哒普利对自发性高血压大鼠左室肥厚和c-Jun表达的影响

目的探讨厄贝沙坦和咪哒普利对自发性高血压大鼠（SHR）左室肥厚和c-Jun表达的影响。方法选用13周龄的SHR 30只,雌性9只,雄性21只,体质量（229±39）g,随机分为3组:SHR组,厄贝沙坦组,咪哒普利组,每组雌性3只,雄性7只。另选同源同系、血压正常的Wistar-Kyoto大鼠（WKY）10只,雌性5只,雄性5只,体质量（206±49）g,作为正常对照组（WKY组）。实验期14周。观察指标:血压、左室质量/体质量（LVW/BW）、左室厚度/体质量、左心室肌c-Jun蛋白及mRNA水平。结果26周龄SHR组血压、LVW/BW与左室厚度/体质量均增高,左心室肌c-Jun蛋白和mRNA的表达明显增加;咪哒普利组、厄贝沙坦组血压、LVW/BW、左室厚度/体质量、左心室肌c-Jun蛋白和mRNA的表达均降低。结论自发性高血压可明显导致心肌肥厚,而咪哒普利、厄贝沙坦可明显降低血压、抑制心肌肥厚的发生。     

福辛普利对SHR左室肥厚和心肌纤维化的影响

目的探讨福辛普利对自发性高血压大鼠(SHR)左心室肥厚(LVH)和心肌纤维化的影响。方法18只16周龄SHR大鼠,随机分为福辛普利治疗组(SHR-F)和SHR空白对照组(SHR-C);另设同源的WKY大鼠8只为正常对照组。治疗组口服福辛普利20mg·kg-1·d-1,给药8周后处死动物,取左心室心肌称重,计算左心室/体重比(LVW/BW),Masson三色法染色观察左心室心肌胶原变化,计算机图像分析测量心肌切片的胶原容积分数(CVF)和血管周围胶原面积(PVCA)。结果SHR空白对照组的SBP、LVW/BW、CVF、PVCA均显著高于WKY对照组(P<0.01),与SHR空白对照组相比,福新普利治疗组能有效降低SHR的SBP,改善SHR左心室肥厚(P<0.01〉并使左心室内膜及心肌小动脉周围的胶原减少(P<0.01〉。结论福辛普利可有效降低SHR血压,部分逆转心肌纤维化和左室肥厚。     

丹芪葛酮对SHR肥厚心肌Gaq/11,PLC-β3及IP3浓度的影响

目的观察丹芪葛酮对肥厚心肌中Gaq/11,PLC-β3蛋白及IP3浓度的干预,并探讨其逆转心肌肥厚的作用机制。方法对自发性高血压大鼠(SHR)行腹主动脉部分缩窄术制作心肌肥厚模型,随机分为非用药组(ND组)、卡托普利组(CAP组)和丹芪葛酮组(DGH组),每组各8只,另设正常Wister大鼠为对照组(CG组)。于连续用药8周后取材,测定全心重/体重(HW/BW)、左室重/体重(LVW/BW)、左心室肌组织中Gaq/11,PLC-β3、蛋白及IP3浓度变化。结果DGH组LVW/BW为(3.48±0.29)g/kg,与ND组比较有统计学意义(P<0.05)。左心室肥厚时,Gaq/11蛋白和PLC-β3蛋白表达无明显性差异,IP3浓度为(2.05±0.52)nmol/L,明显高于CG组的(0.71±0.18)nmol/L(P<0.01),应用丹芪葛酮和卡托普利治疗后,均有明显的干预作用。结论肌醇磷脂途径可能参与心肌肥厚的病理过程,而丹芪葛酮组方有重塑心肌肥厚的作用。     

一氧化氮合酶mRNA在压力超负荷心肌肥厚中的作用

目的:研究一氧化氮合酶(NOS)mRNA在心肌肥厚发生发展中的作用以及卡托普利防治心肌肥厚的机制。方法:采用腹主动脉狭窄术建立压力超负荷心肌肥厚动物模型,应用RT-PCR方法于术后1、2、4周,分别检测对照组、心肌肥厚组和卡托普利组大鼠左心室心肌组织NOS mRNA表达的变化。结果:①与对照组相比,术后1、2、4周心肌肥厚组大鼠左室重/体重(LVW/BW)指标及SBP均显著升高;左心室eNOS mRNA表达降低,iNOS mRNA表达升高,nNOS mRNA表达无明显变化。②与心肌肥厚组相比,术后1、2、4周卡托普利组大鼠LVW/BW及SBP均显著降低;左心室eNOS mRNA表达升高,iNOS mRNA表达降低,接近对照组。结论: eNOS和iNOS参与心肌肥厚的发生发展过程,但二者起不同作用。卡托普利防治心肌肥厚的作用可能与其调节NOS mRNA表达密切相关。     

替米沙坦对自发性高血压大鼠左心室重塑的影响

目的探讨替米沙坦对自发性高血压大鼠(SHR)左心室重塑的影响。方法l6只16周龄雄性SHR,随机分为替米沙坦治疗组和SHR空白对照组;另设同源的WKY大鼠8只为正常对照组。治疗组给予替米沙坦10mg·kg-1·d-1灌胃给药,8周后处死动物,测量左心室心肌厚度并称重,计算左心室与体重比(LVW/BW);通过Van Gieson染色法观察左心室心肌胶原变化,对左心室心肌胶原容积分数(CVF)和血管周围胶原面积(PVCA)进行定性和半定量分析;电镜和HE染色观察左室心肌病理及超微结构。结果与WKY组相比,SHR空白对照组的尾动脉收缩压(SBP)、LVW/BW、左室壁厚度、CVF、PVCA、均显著增高(P<0.01);与SHR空白对照组相比,替米沙坦治疗组能有效降低SHR的SBP,改善左心室肥厚(P<0.01),减少心肌间质及心肌小动脉周围的胶原(P<0.01),组织病理及电镜显示,替米沙坦治疗能显著改善SHR左心室重塑。结论替米沙坦能有效降低SHR血压,改善左心室重塑。     

替米沙坦对自发性高血压大鼠左心室重构的影响

目的 研究替米沙坦对自发性高血压大鼠(SHR)左心室重构的影响.方法 16只12周龄雄性SHR,随机分为替米沙坦组和SHR空白对照组,每组8只;另设同龄Wistar大鼠(WKY)8只为正常对照组.治疗组给予替米沙坦10 mg·kg-1·d-1灌胃给药,饲养8 w后处死动物,测量左心室重量及心肌厚度,计算左心室重量与体重比(LVW/BW);通过Van Gieson染色法观察左心室心肌胶原纤维变化,对左心室心肌胶原容积分数(CVF)和血管周围胶原面积(PVCA)进行分析;电镜和HE染色观察左室心肌超微结构.结果 与正常对照组WKY大鼠相比,SHR空白对照组的尾动脉收缩压(SBP)、LVW/BW、左室壁厚度、CVF、PVCA均显著增高(P＜0.01);与SHR空白对照组相比,替米沙坦组能有效降低SHR的SBP,改善左心室肥厚(P＜0.01),减少心肌间质及心肌小动脉周围的胶原(P＜0.01),组织病理及电镜显示,替米沙坦治疗能显著改善SHR左心室重构.结论 替米沙坦能有效降低SHR血压,改善左心室重构.     

辛伐他汀逆转左室肥厚的作用与抑癌基因PTEN表达的关系

目的观察辛伐他汀逆转自发性高血压大鼠(SHR)左心室肥厚(LVH)的作用及其与抑癌基因第10号染色体缺失的张力蛋白同源区(PTEN)表达的关系。方法16只雄性8周龄SHR测量体重和收缩压后,随机分为SHR治疗组和SHR对照组,分别给予辛伐他汀和安慰剂灌胃治疗,性别、年龄、数量匹配的Wistar大鼠给予安慰剂治疗作为正常对照组,疗程10周,观察辛伐他汀对大鼠收缩压和左心室重量/体重比值(LVW/BW)的影响,采用逆转录聚合酶链式反应(RTPCR)和蛋白免疫印迹法(Westernblot)检测辛伐他汀对心肌组织PTEN表达的影响。结果(1)治疗前两组SHR收缩压无显著差异(P>0.05),均高于Wistar正常对照组大鼠(P<0.01);给予辛伐他汀后,SHR治疗组收缩压(217.3±8.5)mmHg较SHR对照组(220.8±9.9)mmHg略有降低,但无统计学意义(P>0.05),且两组SHR收缩压仍高于Wistar正常对照组大鼠(126.0±5.8)mmHg,差异非常显著(P<0.01)。(2)SHR对照组大鼠的LVM/BW(4.10±0.13)mg/g明显高于Wistar正常对照组(3.04±0.12)mg/g,并有统计学意义(P<0.01),而SHR辛伐他汀治疗组的LVM/BW(3.73±0.08)mg/g较SHR对照组明显下降(P<0.01)。(3)SHR对照组大鼠心肌组织PTEN的mRNA表达水平(0.36±0.04)低于Wistar正常对照组(0.87±0.05),差异非常显著(P<0.01),SHR治疗组大鼠的PTENmRNA表达水平(0.60±0.05)较SHR对照组显著升高,并有统计学意义(P<0.01)。(4)Wistar正常对照组、SHR对照组和SHR治疗组大鼠心肌组织PTEN蛋白表达水平分别为50.53±2.92、24.65±3.89和40.32±4.04,其中SHR对照组明显低于Wistar正常对照组(P<0.01),SHR治疗组则较SHR对照组显著升高(P<0.01)。结论辛伐他汀能够逆转SHR的LVH,其机制可能与PTEN表达水平增加有关。     

瑞舒伐他汀对大鼠肥厚心肌组织PPARγ和NF-κB蛋白表达的影响

目的探讨瑞舒伐他汀对异丙肾上腺素(isoproterenol,Iso)诱导心肌肥厚大鼠心肌组织PPARγ和NF-κB表达的影响及其抑制心肌肥厚,改善心功能的机制。方法 40只雄性SD大鼠随机分为4组:正常对照组、模型组、瑞舒伐他汀组和卡托普利组,每组10只。除正常对照组外,各组背部皮下注射Iso建立心肌肥厚模型。模型制备成功后,瑞舒伐他汀组灌胃给予瑞舒伐他汀4 mg.kg-1.d-1,卡托普利组灌胃给予卡托普利50 mg.kg-1.d-1,其余两组灌胃给予等体积生理盐水。4 w末,分别测定各组大鼠左室收缩压(LVSP)、左室舒张末压(LVEDP)、左室压力上升及下降最大速率(±dp/dt max);测定大鼠体重(BW)、心脏重量(HW)及左心室重量(LVW),计算心脏重量指数(HWI)及左心室重量指数(LVWI);应用病理学方法观察心肌组织形态学改变;Western印迹法测定心肌组织PPARγ和NF-κB亚基p65蛋白表达。结果模型组大鼠LVEDP、HWI、LVWI明显高于正常对照组(P<0.01),LVSP和±dp/dt max明显降低(P<0.01);模型组PPARγ表达明显低于正常对照组(P<0.01),p65表达明显升高(P<0.01);瑞舒伐他汀组和卡托普利组PPARγ表达明显高于模型组(P<0.01),p65表达明显降低(P<0.01);瑞舒伐他汀组和卡托普利组比较,上述指标差异均无统计学意义(P>0.05)。结论瑞舒伐他汀抑制心肌肥厚,改善心功能,其机制与增加PPARγ表达,降低p65表达有关。     

阿托伐他汀对自发性高血压大鼠心肌组织p21表达的影响及其意义

目的:观察阿托伐他汀(ATV)对自发性高血压大鼠(SHR)心肌组织中p21表达的影响,探讨其改善心肌肥厚的可能机制。方法:将16只8周龄SHR随机分为2组(n=8):ATV药物干预组(ATV组)与SHR模型对照组(SHR组),并以8只同周龄Wistar-Kyoto大鼠作为正常对照组(WKY组)。ATV组用ATV 50 mg/(kg·d)灌胃,SHR组与WKY组采用等容量蒸馏水每日同时灌胃。每隔2周测1次血压。10周后,观察大鼠血脂、心肌肥厚指标、p21 mRNA及其蛋白表达的改变。结果:干预10周后,ATV组及SHR组血脂、血压无明显差异。ATV组左室质量指数低于SHR组(P<0.01)。ATV组p21mRNA及蛋白的表达明显高于SHR组(P<0.01)。心肌组织p21mRNA的表达与全心质量与体质量比(HW/BW)呈负相关(r=-0.709,P<0.01),与左室质量与体质量比(LVW/BW)呈负相关(r=-0.665,P<0.01)。结论:ATV可上调SHR肥厚心肌组织中p21的表达,可有效改善左室肥厚。     

胰岛素瘤的解剖分布特点分析

目的胰岛素瘤是最常见的胰腺神经内分泌肿瘤，因其临床表现多样，导致诊断困难。影像学诊断尤其是超声内镜(EUS)在胰岛素瘤的诊断中起着重要作用，拥有较高的敏感性和特异性。本研究拟通过明确胰岛素瘤的解剖分布特点，以期有助于提高影像学的诊断准确率和降低漏诊率，尤其是在教育和培训实践中对于EUS的学习者更具有指导价值。 方法回顾性分析解放军总医院第一医学中心病案资料数据库1993年1月至2019年11月经外科手术、病理确诊为胰岛素瘤的患者的临床资料，检索方法采取搜索术后病理诊断为"胰岛素瘤"的病例，通过查阅病例的方法，提取出胰岛素瘤的大小和解剖分布等数据，进一步分析其特点。 结果共检索到确诊为胰岛素瘤的患者116例，其中，男45例、女71例，年龄13～76岁，平均年龄(44.4±14.85)岁。胰岛素瘤单发110例(94.8%)、多发6例(5.2%)。位置分布：头颈部46例(39.7%)，单发45例、多发1例；体尾部68例(58.6%)，单发65例、多发3例；全胰腺多发2例(1.7%)。病变大小特点：最大径0.4～3.4 cm，平均大小(1.53±0.58)cm。≤1 cm 29例、>1 cm而≤1.5 cm41例、>1.5 cm而≤2.0 cm28例，≤3 cm 15例，>3 cm 3例。年龄与肿瘤的大小相关，≤44岁患者肿瘤平均大小为(1.36±0.51)cm、>44岁患者肿瘤平均大小为(1.70±0.60)cm，P<0.05。头颈部的肿瘤大于体尾部的肿瘤，头颈部肿瘤平均大小(1.66±0.63)cm，体尾部(1.42±0.52)cm，P<0.05。 结论胰岛素瘤在胰腺体尾部较头颈部更好发；绝大多数单发，但可以全胰腺多发；多数小于1.5 cm，肿瘤的大小与患者年龄和肿瘤的解剖分布相关。     

Pathogenesis of carcinoma of the papilla of Vater

Most adenomas and carcinomas of the small intestine and extrahepatic bile ducts arise in the region of the papilla of Vater. In familial adenomatous polyposis (FAP) it is the main location for carcinomas after proctocolectomy. In many cases symptoms due to stenosis lead to diagnosis at an early tumor stage. In about 80%, curative intended resection is possible. Operability is the most relevant prognostic factor. Most ampullary carcinomas resp. carcinomas of the papilla of Vater develop from adenomatous or flat dysplastic precursor lesions. They can be sited in the ampulloduodenal part of the papilla of Vater, which is lined by intestinal mucosa. They also can develop in deeper parts of the ampulla, which are lined by pancreaticobiliary duct mucosa. Intestinal-type adenocarcinoma and pancreaticobiliary-type adenocarcinoma represent the main histological types of ampullary carcinoma. Furthermore, there exist unusual types and undifferentiated carcinomas. Many carcinomas of intestinal type express the immunohistochemical marker profile of intestinal mucosa (keratin 7?, keratin 20+, MUC2+). Carcinomas of pancreaticobiliary type usually show the immunohistochemical profile of pancreaticobiliary duct mucosa (keratin 7+, keratin 20?, MUC2?). Even poorly differentiated carcinomas, as well as unusual histological types, may conserve the marker profile of the mucosa they developed from. These findings underline the concept of histogenetically different carcinomas of the papilla of Vater which develop either from intestinal- or from pancreaticobiliary-type mucosa of the papilla of Vater. Molecular alterations in ampullary carcinomas are similar to those of colorectal as well as pancreatic carcinomas, although they appear at different frequencies. In future studies, molecular alterations in ampullary carcinomas should be correlated closely with the different histologic tumor types. Consequently, the histologic classification should reflect the histogenesis of ampullary tumors from the two different types of papillary mucosa.     

Demonstration of the mechanism of action of biguanides

Summary Palmitic acid oxidation in rat diaphragm homogenate is depressed by biguanide concentrations that are still incapable of inhibiting oxidative phosphorylation. Glucose oxidation is not directly effected by the same biguanide concentrations: however, the inhibitory effect of palmitic acid on glucose oxidation is partly removed by biguanides. Inhibition of fatty acid oxidation, which accounts for most of the metabolic effects caused by these drugs, can be regarded as the fundamental mechanism of action of biguanides. There is some evidence suggesting that these drugs might interact with carnitine, thus preventing long-chain fatty acids from being transported across the mitochondrial membrane to the site of oxidation. Traduzione a cura degli AA.     

Lack of correlation of degree of villous atrophy with severity of clinical presentation of coeliac disease

BACKGROUND AND AIM: Both the clinical presentation and the degree of mucosal damage in coeliac disease vary greatly. In view of conflicting information as to whether the mode of presentation correlates with the degree of villous atrophy, we reviewed a large cohort of patients with coeliac disease. PATIENTS AND METHODS: We correlated mode of presentation (classical, diarrhoea predominant or atypical/silent) with histology of duodenal biopsies and examined their trends over time. RESULTS: The cohort consisted of 499 adults, mean age 44.1 years, 68% females. The majority had silent coeliac disease (56%) and total villous atrophy (65%). There was no correlation of mode of presentation with the degree of villous atrophy (p=0.25). Sixty-eight percent of females and 58% of males had a severe villous atrophy (p=0.052). There was a significant trend over time for a greater proportion of patients presenting as atypical/silent coeliac disease and having partial villous atrophy, though the majority still had total villous atrophy. CONCLUSIONS: Among our patients the degree of villous atrophy in duodenal biopsies did not correlate with the mode of presentation, indicating that factors other than the degree of villous atrophy must account for diarrhoea in coeliac disease.     

血吸虫童虫生长发育及其机制的研究进展

血吸虫童虫是宿主免疫系统攻击的重要靶标,包括皮肤型、肺型和肝门型童虫。宿主分子对童虫生长发育具有重要作用。童虫生长发育机制包括免疫调节、信号转导、性别发育及凋亡等。肌动蛋白、组织蛋白酶、烯醇化酶和葡萄糖基转移酶等分子为血吸虫童虫生长发育的重要分子。本文对血吸虫童虫生长发育及其机制的研究进展做一综述。     

氯硝柳胺悬浮剂的毒性评价

目的评价氯硝柳胺悬浮剂的毒性，为现场大规模应用灭螺提供依据。方法按照中华人民共和国国家标准GB 15670-1995《农药登记毒理学试验方法》和鱼类毒性试验方法进行。结果经口、经皮肤的LDso雌、雄性大鼠均>5 000 mg/kg，经呼吸道的LCso雌、雄性大鼠均>5 000mg/m3，该药经口、经皮肤、经呼吸道毒性均属微毒类药物；兔眼用药后，观察期内无不良反应，对眼无刺激性；皮肤用药后对皮肤无刺激性。与氯硝柳胺原药、氯硝柳胺乙醇胺盐原药和氯硝柳胺乙醇胺盐可湿性粉剂相比，氯硝柳胺悬浮剂对鱼急性毒性最低。结论氯硝柳胺悬浮剂属微毒类药物，对鱼的毒性低于其乙醇胺盐可湿性粉剂，适合于现场应用。     

124例耐多药结核分枝杆菌基因突变特征分析

目的对临床分离的耐多药结核分枝杆菌相关基因的突变特征进行分析。方法对124例耐多药结核分枝杆菌以及50株敏感株的耐药相关基因(包括异烟肼inh A、kat G、oxyR-ahp C间隔区以及利福平rpo B)进行序列测定,分析其基因突变情况。结果异烟肼耐药inh A基因突变率为14.5%;kat G基因突变率为70.2%(87/124),主要位于315位;oxyR-ahp C间隔区突变率为15.3%;inh A、kat G两种基因同时突变率75.0%,三种基因同时突变率为89.5%。利福平rpo B基因突变的检出率高达95.2%,突变主要发生在531、526、516位点。结论我省耐多药菌异烟肼耐药相关基因最常见突变为kat G 315、inh A C-T(-15)、axyR-ahp C间隔区(-10)C-T,利福平为rpo B531、526、516。结合MDR-TB耐药相关基因的特征分析,可以建立一种快速、准确、特异的适合于我省的检测结核菌耐多药性的新方法。     

Assessment of quality of life of parents of children with juvenile chronic arthritis

The aim of the study was to assess the quality of life (QOL) and the psychological status of parents of children with juvenile chronic arthritis (JCA). The QOL, anxiety and depression of the parents of 28 children with JCA were evaluated and compared to those of the parents of 28 healthy children. Mothers of JCA children and mothers of healthy children reported similar QOL. The reported anxiety and depression levels were similar for mothers and fathers in both groups. The parents of children with pauciarticular-type JCA reported lower QOL and higher levels of anxiety and depression than the parents of children with other types, namely polyarticular and systemic JCA. These findings may be explained by the fact that the pauciarticular patients had shorter disease duration and were less frequently seen in the outpatient clinic. The QOL of mothers of children with JCA was found to be slightly impaired in the group of children with pauciarticular JCA. Future larger studies are needed to confirm these results, as the number of subjects in the three groups was rather low. Received: 26 September 2001 / Accepted: 8 February 2002     

Numerical Simulation of the Effect of Rate of Change of Glucose on Measurement Error of Continuous Glucose Monitors

Background

A 5-day in-patient study designed to assess the accuracy of the FreeStyle Navigator® Continuous Glucose Monitoring System revealed that the level of accuracy of the continuous sensor measurements was dependent on the rate of glucose change. When the absolute rate of change was less than 1 mg•dl⁻¹•min⁻¹ (75% of the time), the median absolute relative difference (ARD) was 8.5%, with 85% of all points falling within the A zone of the Clarke error grid. When the absolute rate of change was greater than 2 mg•dl⁻¹•min⁻¹ (8% of the time), the median ARD was 17.5%, with 59% of all points falling within the Clarke A zone.

Method

Numerical simulations were performed to investigate effects of the rate of change of glucose on sensor measurement error. This approach enabled physiologically relevant distributions of glucose values to be reordered to explore the effect of different glucose rate-of-change distributions on apparent sensor accuracy.

Results

The physiological lag between blood and interstitial fluid glucose levels is sufficient to account for the observed difference in sensor accuracy between periods of stable glucose and periods of rapidly changing glucose.

Conclusions

The role of physiological lag on the apparent decrease in sensor accuracy at high glucose rates of change has implications for clinical study design, regulatory review of continuous glucose sensors, and development of performance standards for this new technology. This work demonstrates the difficulty in comparing accuracy measures between different clinical studies and highlights the need for studies to include both relevant glucose distributions and relevant glucose rate-of-change distributions.     

治疗高血压药物的经济学评价

重视高血压治疗中的经济学评价,对利用我国有限的卫生资源来遏制高血压对人民群众的危害有着重要的现实意义。药物经济学对于药物治疗的成本和治疗的结果给予同样的关注。因为治疗高血压的费用,不仅涉及药物价格,还包括患者的危险水平,降压疗效和对临床终点事件的影响,以及治疗的依从性和安全性。因此药物经济学更强调整体成本和价-效比。低危病人,若非药价低廉,治疗的价-效比不够理想。而在高危的患者,价-效比越小越经济而不是药费越便宜越好。