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1.
目的 制备99Tcm标记的含有精氨酸-甘氨酸-天冬氨酸(Arg-Gly-Asp,RGD)序列的环肽四聚体99Tcm-联肼尼克酰胺(HYNIC)-E{E[c(RGDfK)]2}2,评价其在整合素αvβ3表达阳性的荷人神经胶质瘤裸鼠模型的生物分布和显像.方法 以HYNIC为双功能螫合剂,以三羟甲基甘氨酸(tricine)和三苯基膦三磺酸钠(TPfffS)为协同配体,采用两步法制备99Tcm-HYNIC-E{E[c(RGDfK)2}2.通过体外受体竞争结合实验比较e(RGDyK)单体、HYNIC-E[c(RGDfK)2二聚体和HYNIC-E{E[c(RGDfK)]2}2四聚体与整合素αvβ3亲和力.生物分布实验数据显示,99Tcm-HYNIC-E{E[c(RGDtK)]2}2主要经肾排泄;注射后1h,肿瘤对99Tcm-HYNIC-E{E[c(RGDfK)]2}2的摄取为99Tcm-HYNIC-E[c(RG-DfK)]2的2倍,分别为(10.32±0.07)%ID/g和(5.15±O.52)%ID/g,与体外受体竞争结合实验数据相一致;注射后4h,肿瘤对99Tcm-HYNIC-E{E[c(RGDfK)]2}2的摄取仍达(9.35.4±1.35)%ID/g,表明标记物在肿瘤中的滞留时间足够长.r显像结果显示,注射后1h肿瘤清晰可见.注射后4h显像效果更佳.结论 99Tcm-HYNIC-E{E[c(RGDfK)]2}2具有较高的肿瘤摄取和较长的肿瘤滞留时间,可以用于整合素αvβ3表达阳性肿瘤的显像;放射性核素(如90Y)标记的RGD环肽四聚体可用于整合素(αvβ3表达阳性肿瘤的治疗.  相似文献   

2.
目的制备^99Tc^m标记的含RGD序列的^99Tc^m-联肼尼克酰胺(HYNIC)-c(RGDfK)环肽单体,评价其在整合素表达阳性的肺腺癌严重联合免疫缺陷(SCID)小鼠肿瘤模型中的生物学分布,并进行显像研究。方法(1)以HYNIC为双功能螯合剂,以三羟甲基甘氨酸(tricine)和乙二胺二乙酸为协同配体,采用二步法制备^99Tc^m标记HYNIC—c(RGDfK),进行细胞结合实验,测定标记物生物学活性;(2)将荷A549肺腺癌模型小鼠分为7组[第7组作为竞争性抑制组,注射显像剂前0.5h先注射HYNIC-c(CRDGfk)100μg],每组5只,经尾静脉注射7.4MBq的^99Tc^m-HYNIC-c(RGDfK),于注射后0.5,1,2,4,8,12h处死,计算荷A549肺腺癌小鼠模型各脏器%ID/g,同时采用ROI技术研究^99Tc^m-HYNIC—c(RGDfK)在小鼠体内的生物学分布,计算不同时间点的T/NT比值(NT选取肌肉);(3)取6只荷瘤裸鼠,其中3只为竞争性抑制组,经尾静脉注射7.4MBq的^99Tc^m-HYNIC—c(RGDfK),于注射后0.5,1,2,4,8,12h进行静态1显像。结果^99Tc^m-HYNIC—c(RGDfK)的标记率〉90%,放化纯〉95%。^99Tc^m-HYNIC—c(RGDfK)与A549肺腺癌细胞特异性结合率最高为36.14%,体内分布实验显示^99Tc^m-HYNIC—c(RGDfK)在肾的摄取率始终高于20%ID/g,注射后0.5h肿瘤%ID/g为10.52±1.48,8h为17.26±2.81,12h为8.93±0.90,竞争性抑制组注射后0.5h为2.29±0.85。通过ROI技术测得T/NT在8h达6.87。注射后1h肿瘤可显影,4~8h显影更清晰。结论^99Tc^m标记HYNIC—c(RGDfK)易于制备,具有良好的靶向性。  相似文献   

3.
目的 评价引入2个聚乙二醇(PEG4)对精氨酸-甘氨酸-天冬氨酸(RGD)环肽二聚体(Dimer:E[c(RGDfK)]2)体外受体结合亲和力和体内药代动力学特征的影响,以及99Tcm标记2PEG4-Dimer用于整合素αvβ3阳性肿瘤显像的前景.方法 用免疫组织化学实验测定U87MG人神经胶质瘤细胞以及肿瘤组织中整合素αvβ3的表达.通过U87MG细胞受体竞争结合实验测定RGD环肽单体c(RGDyK)、联肼尼克酰胺(HYNIC)-Dimer和HYNIC-2PEG4-Dimer对125I-c(RGDyK)的半数抑制浓度(IC50).采用无亚锡一步法制备99Tcm-HYNIC-Dimer和99Tcm-HYNIC-2PEG4-Dimer,评价"TcmHYNIC-2PEG4-Dimer在荷U87MG瘤裸鼠的生物分布并进行γ显像.采用非配对t检验法对实验数据进行分析.结果 U87MG细胞和荷瘤裸鼠肿瘤组织中高表达整合素αvβ3.HYNIC-2PEG4-Dimer比c(RGDyK)和HYNIC-Dimer有更高的整合素αvβ3亲和力(IC50分别是0.8,27和2.4 nmol/L).99Tcm-HYNIC-Dimer和99Tcm-HYNIC-2PEG4-Dimer的99Tcm标记率均>95%,经Sep-Pek C18柱纯化后其放化纯>99%.生物分布实验显示,2种标记物均主要经肾排泄,在注射后2h,肿瘤对99Tcm-HYNIC-2PEG4-Dimer的摄取为99Tcm-HYNIC-Dimer的2.7倍[(5.71±0.96)%ID/g和(2.10±0.50)%ID/g],t=4.80,P<0.05,与体外受体竞争结合实验数据相一致.γ显像结果显示,注射99Tcm-HYNIC-2PEG4-Dimer后0.5 h肿瘤即清晰可见,随时间延长,体内放射性本底明显减低,显像对比度增高.结论 99Tcm-HYNIC-2PEG4-Dimer有希望用于整合素αvβ3阳性肿瘤显像.  相似文献   

4.
目的证明^99 Tc^m标记联肼尼克酰胺(HYNIC)多肽“显像剂”文库是^99 Tc^m显像剂研制中的有效方法。方法八肽组合文库采用人工点阵方式合成。HYNIC多肽通过C末端以及双B丙氨酸(连接体)共价连接在纤维膜上。用阻断剂阻断非特异结合位点后,将膜文库和人重组热休克蛋白70(HSP70)温育,冲洗。用生物素-亲和素法和抗体法筛选文库。对筛选阳性多肽化合物进行再合成、^99 Tc^m标记(以三羟甲基甘氨酸为辅助配体)以及体内分析。将人肺癌细胞株A549和H460接种于雌性裸鼠胸壁皮下,用于体内研究。结果^99 Tc^m标记文库显示,“显像剂”文库的质量较好。由于天冬酰胺-亮氨酸-亮氨酸-精-氨酸-亮氨酸-苏氨酸-甘氨酸多肽(NLLRLTG)对HSP70家族蛋白具有高度特异性,因此,采用^99 Tc^m-HYNIC—NLLRLTG为对照组。经筛选获得的15种阳性多肽化合物中,有8种^99 Tc^m化合物在体内肿瘤中的分布优于对照组,其中^99 Tc^m HYNIC-谷氨酰胺-甘氨酸-缬氨酸-亮氨酸-苏氨酸.甘氨酸-苏氨酸-精氨酸多肽(QGVLTGTR)在体内肿瘤中的分布最佳。活性肽NLLRLTG替代实验和肿瘤热疗研究表明,^99 Tc^m HYNIC—QGVLTGTR具有HSP70结合肽活性。结论^99 Tc^m标记HYNIC八肽化合物“显像剂”文库的设计可能为多肽显像剂的研制提供一种模式。  相似文献   

5.
目的探讨^99Tc^m标记针对小鼠双微体扩增基因(MDM2)mRNA的ASON(MDM2反义探针)用于前列腺癌无创性基因显像的价值。方法以HYNIC为螯合物,对含MDM2mRNA某段序列的ASON、错义寡核苷酸(ASONM)进行^99Tc^m标记,检测标记率及放化纯。建立荷人前列腺癌LNCaP裸鼠肿瘤模型,分为3组(每组10只),进行^99Tc^m-HYNIC—ASON和^99Tc^mHYNIC—ASONM、^99Tc^mO4^-(对照)肿瘤显像。测量肿瘤/对侧肢体(T/M)比值,采用单因素方差分析对测量数据进行统计学分析。结果ASON的^99Tc^m标记率为(65.15±2.05)%,ASONM的^99Tc^m标记率为(64.93±2.18)%。^99Tc^m-HYNIC—ASON和^99Tc^m-HYNIC—ASONM经纯化后,放化纯均达90%以上。不同探针注射后1、4和10h时,^99Tc^m-HYNIC—ASON组T/M比值分别为3.217±0.125、3.749±0.201和4.028~0.186;^99Tc^m HYNIC—ASONM组分别为1.579±0.128、1.715±1.140和1.683±0.139;对照组分别为2.146±0.132、1.847±0.124和1.528±0.152.^99Tc^m-HYNIC—ASON1、4、10hT/M比值与对照组和错义组差异均有统计学意义(F=213.37~235.41,t=3.527~4.738,均P〈0.01),而^99Tc^m-HYNIC—ASONM组各T/M比值与对照组差异均无统计学意义(t=2.154、2.287和2.236,均P〉0.05)。结论^99Tc^m标记的MDM2反义探针可在荷人前列腺癌裸鼠模型的肿瘤组织中特异性聚集,可以在早期对前列腺癌进行无创性的基因诊断。  相似文献   

6.
整合素αvβ3高表达于肿瘤细胞和肿瘤新生血管内皮细胞表面,而在正常组织和成熟血管内皮细胞表面呈低水平表达或不表达,整合素αvβ3能够与体内外含精氨酸-甘氨酸-天冬氨酸(RGD)序列的物质发生特异性结合。通过对RGD肽进行结构修饰、多聚化等来构建体内理化性能稳定的RGD肽和RGD-蛙皮素等融合肽,再通过不同的偶联剂介导完成RGD肽的不同放射性核素(^18F、^111In、^64Cu、^68Ga、^125I、^99Tc^m、^123I、^86Y等)标记,成为近年来肿瘤靶向显像的研究热点,部分临床实验正在国内外进行有效开展。通过PET/CT、SPECT/CT和PET/MRI多模态显像定量检测肿瘤整合素αvβ3受体的表达水平,来完成抗肿瘤新生血管生成治疗患者的筛选、疗效预测和实时监测,已成为近年来研究的焦点和新的发展方向。  相似文献   

7.
目的 制备特异性整合素αvβ3探针[^18F]氟化铝-匹仑吉肽(^18F-Al-NOTA-PRGD2),探讨其用于甲状腺乳头状癌(PTC) PET显像的可行性.方法 采用氟化铝新策略制备18F-Al-NOTA-PRGD2.取新鲜切除的人PTC肿瘤组织接种于裸鼠右腋下,制得荷人PTC裸鼠模型.再分别取人PTC标本及毗邻的正常组织、荷瘤裸鼠移植瘤行整合素αvβ3免疫组织化学染色.荷瘤裸鼠(n=5)尾静脉注射1.1 MBq ^18F-Al-NOTA-PRGD2后30、60和120 min分别行microPET显像,通过ROI技术计算肿瘤和主要脏器的放射性摄取值(% ID/g),并通过阻断实验验证其特异性.另取15只荷瘤裸鼠研究其注药后30、60及120 min生物分布,计算放射性摄取值(%ID/g).用两样本t检验进行统计学处理.结果 成功制备^18F-Al-NOTA-PRGD2,标记率>45%.免疫组织化学染色证实人PTC标本和裸鼠移植瘤组织整合素αvβ3染色均呈棕褐色阳性表达,人PTC毗邻正常组织不表达.荷瘤裸鼠注射^18 F-Al-NOTA-PRGD2后行microPET显像示,肿瘤清晰可见,且与周围组织对比度良好.注射后30、60、120 min肿瘤对显像剂的摄取值分别为(2.81±0.35)、(2.45±0.27)和(1.80±0.21) %ID/g.PRGD2阻断后,注射^18F-Al-NOTA-PRGD2后60 min肿瘤对显像剂的摄取值降为(0.51±0.05) %ID/g.荷瘤裸鼠生物分布实验示,注射显像剂后30、60、120 min肿瘤摄取值分别为(3.09±0.25)、(2.75±0.37)和(1.90±0.16) %ID/g,与microPET显像基本一致(t=1.456、1.465和0.847,均P>0.05).^18F-Al-NOTA-PRGD2在血液和肌肉中清除快,注射后60 min肿瘤与血液和肌肉的摄取比值分别为6.15±0.45和7.86±0.56.结论 ^18F-Al-NOTA-PRGD2制备简单,放化纯高,可有效监测PTC中整合素αvβ3表达水平;其PET显像有望为研究PTC整合素αvβ3受体相关机制提供一种新方法.  相似文献   

8.
目的探讨局部注射正五价^99 Tc^m标记的二巯基丁二酸[^99 Tc^m(V)-DMSA]检测口腔癌颈部淋巴结转移灶的可行性,为制定合理的口腔癌颈淋巴清扫术式提供参考。方法原发口腔鳞状细胞癌患者30例,癌周分点注射^99 Tc^m(V).DMSA,行头颈部断层和平面显像,寻找异常放射性浓聚区域,以ROI技术分析,将结果和术后病理检查结果比较。结果局部注射^99 Tc^m(V).DMSA检测颈部淋巴结转移灶的灵敏度为84.6%(11/13),特异性为82.4%(14/17),准确性为83.3%(25/30)。结论癌周局部注射^99 Tc^m(V)-DMSA检测口腔癌颈淋巴结转移的灵敏度高,准确性好,操作简便。  相似文献   

9.
何杨  吴翼伟  阮长耿 《中华核医学杂志》2004,24(5):276-278,i004
目的研究^99Tc^m标记抗人粒细胞单克隆抗体SZ-102在荷人胰腺癌裸鼠体内显像及生物分布。方法以2-亚氨基噻吩盐酸盐(2-IT)修饰SZ-102,^99Tc^m-葡庚糖酸钠(GH)配体交换法标记SZ-102,经裸鼠尾静脉注入^99Tc^m-SZ-102后4、8和24h分别测定荷瘤小鼠体内组织的放射性分布,并于1和4h对裸鼠进行γ显像。结果γ显像及生物分布示,^99Tc^m-SZ-102静脉注入荷瘤鼠后1h,肿瘤清晰显影,随时间延长,瘤体内放射性越来越浓,且瘤组织与非瘤组织的放射性比值(T/NT)也逐渐增高,各时相肿瘤每克组织百分注射剂量率(%ID/g)高于注射^99Tc^m-IgG的对照组。结论^99Tc^m-SZ-102具有活体内定位导向能力,显像时间短。  相似文献   

10.
99Tcm-HYNIC-Annexin V的制备及其在健康小鼠体内的分布   总被引:4,自引:1,他引:3  
目的制备人膜联蛋白V(Annexin V),应用联肼尼克酰胺(HYNIC)偶联后进行^99Tc^m标记,评价^99Tc^m-HYNIC-Annexin V在健康小鼠体内的分布。方法采用基因工程方法构建Annexin V的原核载体并诱导其表达,与自行合成的双功能螯合剂HYNIC偶联,并进行^99Tc^m标记。测定^99Tc^m-HYNIC-Annexin V的标记率、放化纯,并研究其在健康小鼠体内的生物分布特性。结果Annexin V在大肠杆菌中获得稳定表达,经十二烷基硫酸钠聚丙烯酰胺凝胶电泳(SDS-PAGE)及Western Blotting检测,得到纯度较高的蛋白质。Annexin V经HYNIC偶联后,其^99Tc^m标记率可达90%左右,放化纯〉90%。小鼠体内分布结果表明,^99Tc^m-HYNIC-Annexin V血液清除迅速,主要从肾脏和肝脏排泄。结论Annexin V可在原核生物中稳定表达。其与HYNIC偶联后,^99Tc^m-标记率和放化纯较高,方法简单,条件温和。  相似文献   

11.
Fibromyalgia is a syndrome manifested by chronic, diffuse muscu-loskeletal aching and soreness, palpable muscle tender points, and other symptoms. Standardized clinical diagnostic criteria have recently been developed. Skeletal muscle has been postulated as the end organ in this disease. Biochemical, histologic, electromyographic, and conventional radiographic studies have demonstrated no definitive abnormality. This study sought to establish whether magnetic resonance (MR) imaging could demonstrate any abnormality in these patients. Eighteen patients were entered in the study, 14 of whom were able to complete their examinations. T1 -weighted, T2-weighted, gradient-echo, and STIR (short-tau inversion-recovery) sequences were performed in all patients, with selected patients examined with T1weighted, gadopentetate dimeglu-mine-enhanced sequences. The trapezius and suboccipital regions were imaged in patients who, clinically, had active fibro-myalgia. No abnormalities could be detected. The authors conclude that the conventional MR imaging used in this study was unable to depict any primary skeletal muscle abnormality in fibromyalgia.  相似文献   

12.
Collagen is a major component of the extracellular matrix and a determinant of the elastic behavior of the human aorta. To investigate the changes found in aneurysmal degeneration, the authors studied the solid-state hydrogen-1 nuclear magnetic resonance line shape of collagen in aneurysms and normal human aortas. A three-component decomposition of the free induction decay was performed, with collagen characterized by a T2 of about 18 μsec. The second moment of the collagen line shape was found to be increased in aneurysms (5.3 vs 4.8 G2), while, correspondingly, the T2 of collagen was lower in aneurysms (16.3 vs 17.7μsec). This corresponds to a modification of collagen structure and molecular motion. Collagen concentration was lower in nondiseased aortic walls (9.4% vs 7.3%). These results are discussed in reference to the contradictory conclusions in the current literature. The increase in collagen and the modification of its structure and molecular motion are explained by the need to resist an increasing tangential tension due to increased aortic diameter and diminished wall thickness in aneurysms and by intercalation or site binding in the helices or electric dipolar interactions in the less mobile side groups.  相似文献   

13.
14.
The potential of using fast magnetic resonance (MR) imaging in conjunction with apnea-induced blood deoxygenation for the noninvasive monitoring of relative perfusion in the rat abdomen has been studied with two experimental models: glycer-ol-induced focal renal ischemia and transplanted liver tumor. Gradient-echo echo-planar imaging (GRE-EPI) (TE of 20 msec at 2 T) of liver and kidney was performed before, during, and after a 60-second apnea episode and then was followed in the same rat by contrast-enhanced (a) GRE-EPI and (b) T1-weighted spin-echo imaging (TR msec/TE msec = 200/6) with polylysine-(gadolmium-DTPA [diethylenetriaminepentaacetic acid]). The results indicate that a noninvasive vascular challenge due to apnea can be used for the detection of focal tissue perfusion abnormalities in rat kidney and liver tumor.  相似文献   

15.
乳腺高危病变包括良性病变及原位癌,具有发生乳腺癌的风险。高危病变首诊主要依赖于穿刺活检,但首诊后存在一定的病变升级率。对于不同的高危病变,如不典型导管增生(ADH)、乳头状瘤伴不典型增生、放射状瘢痕、小叶原位癌(LCIS)、不典型小叶增生(ALH)、黏液囊肿样病变、平坦上皮非典型增生等,乳腺X线检查的诊断及处理原则并不完全相同。就乳腺X线检查对高危病变的诊断、处理、预后评估的研究进展予以综述。  相似文献   

16.
The goal of the study was to establish normal carotid artery flow rates in left-handed and right-handed individuals as a standard against which patients with carotid artery disease could be compared. Antegrade and retrograde flow were measured in the ascending aorta, in the right and left common, internal, and external carotid arteries, and in the vertebral arteries of 12 healthy subjects. Five subjects were right-handed, five left-handed, and two ambidextrous. Measured flow rates were as follows: common carotid arteries, 360–557 mL/min (mean [± standard deviation], 465 mL/min ± 52); internal carotid arteries, 132–367 mL/min (mean, 265 mL/min ± 60); external carotid arteries, 113–309 mL/min (mean, 186 mL/min ± 51); vertebral arteries from 133–308 mL/min (mean, 244 mL/min ± 43); and cerebral circulation, 546–931 mL/min (mean, 774 mL/min ± 134). All right-handed subjects had higher flow rates in the left internal carotid artery than in the right, and all left-handed subjects had higher flow rates in the right internal carotid artery (P =.007). There were no significant differences in left and right common carotid artery flow rates between left- and right-handed subjects. The standard deviation of a single measurement was 5%. The flow rates were similar to those obtained previously with other techniques and could be used as a normal standard.  相似文献   

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18.
AIMS: To demonstrate a practical method to address new Department of Health requirements for assessment and appraisal. METHOD: This process was developed within the department to incorporate workload, clinical incidents and 360 degrees questionnaires to assess performance and working with departmental staff as preliminaries to an appraisal interview. CONCLUSION: Review of 2 years' process has resulted in minor amendments but there was general agreement that the parameters encompassed were practical and useful.  相似文献   

19.
Objective To compare the radiological findings of heterozygous and homozygous subjects with synpolydactyly (SPD) and to discuss their unusual bone formations.Design and patients Families with hand and foot SPD were examined. Genetic analysis was performed with blood samples and the pedigree was constructed. The affected individuals, especially those with distinctive phenotypic features, were invited to our orthopaedics clinic for further diagnostic studies. All participants underwent detailed clinical and X-ray examinations.Results Of the invited patients, 16 (five female and 11 male; age range 4–37 years, mean age 10.75 years) were included in our study, and hand and foot radiographs were obtained. All subjects had bilateral hand radiographs (32 hands), and 14 had bilateral foot radiographs (28 feet). Genetic analysis revealed 12 heterozygote (75%) and four (25%) homozygote phenotypes. Among patients enrolled into the study nine (three homozygotes, six heterozygotes) had SPD of both hands and feet bilaterally (tetrasynpolydactyly). Six unusual bone formations were observed in the hands and feet: delta phalanx, delta metacarpal/metatarsal, kissing delta phalanx, true double epiphysis, pseudoepiphysis and cone-shaped epiphysis. There were major differences in radiological and clinical manifestations of homozygote and heterozygote phenotypes. The homozygous SPD presented with very distinctive unusual bone formations.Conclusion The existence and variety of unusual bones may indicate the severity of penetrance and expressivity of SPD.This paper was presented as an EPOS at the 11th Annual Meeting of the ESSR 2004 in Augsburg, Germany  相似文献   

20.

Purpose

To evaluate the significance of dynamic contrast enhanced MRI (DCE-MRI) and whole body MRI (WB-MRI) in the diagnosis, prognosis and assessment of therapy for patients with monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM).

Materials and methods

The retrospective study includes 219 patients providing 463 WB-MRI and DCE-MRI investigations for the subgroups MGUS (n = 70), MM active disease (n = 126; this includes 70 patients with new diagnosis of MM, according to the International Staging System (ISS): 41.4% ISS stage I, 20.0% ISS stage II, 7.1% ISS stage III, 31.4% insufficient for staging; and 56 patients with ‘(re-)active disease’: 16.07% relapse, 32.14% progressive disease and 51.79% stable disease) and MM remission (n = 23; 60.87% complete remission, 17.39% very good partial remission and 21.74% partial remission). Investigations of patients with hereditary multiple exostoses (n = 5), neurofibromatosis (n = 7) and healthy persons (n = 9) were added as control subjects (n = 21). WB-MRI evaluation was done by evaluating thirteen skeletal regions, providing a ‘skeletal score’. DCE-MRI images of the spine, were analyzed with regions-of-interest and time-intensity-curves (TIC).

Results

All TIC parameters can significantly differentiate between the predefined subgroups (p < 0.001). One hundred days after autologous stem cell transplantation a 75% decrease of the slope wash-in value (p < 0.001) can be seen. A cubic regression trend between ‘skeletal score’ and slope wash-in (adj.R2 = 0.412) could demonstrate a significant increase bone marrow perfusion if MM affects more than 10 skeletal regions (p < 0.001), associated with a poorer prognosis (p < 0.001).

Conclusion

DCE-MRI evaluation of the spine is useful for diagnosis of MM, follow-up after stem cell transplantation and evaluation of disease activity. A combined evaluation with WB-MRI and DCE-MRI provides additional micro-vascular information on the morphologic lesions and could help categorize patients with MM in two different groups to offer useful therapeutic and prognostic advise.  相似文献   

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