纯化的自体CD34+细胞移植治疗多发性骨髓瘤的临床观察

目的采用CD34+细胞体外分选技术对多发性骨髓瘤患者进行自体CD34+细胞移植,以降低自体移植后肿瘤复发率.方法对1例多发性骨髓瘤患者采用CliniMACS临床型细胞富集仪,利用磁性分选技术收集CD34+细胞,患者于预处理后,输注分选后的CD34+细胞.结果 CD34+细胞体外纯化富集可使回输CD34+细胞中位数达3.9×106/kg,CD34+细胞回收率为35%,纯度达到97.6%;移植后,患者于+14 d时,中性粒细胞数＞0.5×109/L,+35 d时血小板＞20×109/L,提示造血重建.结论 CD34+细胞移植后获得迅速、稳定的造血重建.体外CD34+细胞纯化富集后移植可望提高多发性骨髓瘤患者自体移植疗效.     

癌光啉体外净化骨髓中残留白血病变后行自体骨髓移植治疗白血病

目的 :为减少白血病患者自体骨髓移植后白血病复发率和提高长期无病存活率。方法 :采用缓解期急性非淋巴细胞白血病患者的骨髓细胞在体外经处理后用癌光啉 (浓度为 10 μg/ ml)加光照净化 ,待患者完成预处理后回输给自身。结果 :10例急性髓细胞白血病患者接受了本净化方法后移植治疗。净化后输入有核细胞中位数1.3 0 ( 0 .7～ 2 .4 5 )× 10 8/ kg,CD3 4 细胞中位数 2 .3 9( 0 .74～ 4 .0 6)× 10 6/ kg,CFU- GM中位数 1.4 4( 0 .3 2～4 .65 )× 10 4/ kg。 10例中 9例造血功能重建 ,WBC升到 >1.0× 10 9/ L中位数时间 2 0 ( 15～ 4 3 ) d,>2 .0×10 9/ L 中位数时间 3 0 ( 2 1～ 5 5 ) d,BPC>5 0× 10 9/ L 中位数时间 4 6( 2 5～ 62 ) d。经中位 2 6个 ( 2 0～ 64 )月随访 ,有 6例仍无病存活 ;3例复发 ,其中 2例复发后失去随访 ;1例嗜碱细胞性白血病经化疗再次取得缓解 ,至今 CR2后又无复发存活 14个月 ;1例死于与移植相关并发症。结论 :初步结果表明 ,用癌光啉加光照净化自体骨髓中残留白血病细胞后行自体骨髓移植治疗白血病是一种安全而有潜力的方法     

CD34+造血干细胞混合CD3+T细胞移植分离移植物抗宿主病和移植物抗白血病效应

目的探讨在异基因造血干细胞移植中能否采用纯化CD34+造血干细胞混合一定量纯化CD3+T细胞移植达到既控制移植物抗宿主病(GVHD)又保留移植物的抗白血病效应(GVL). 方法 (C57BL/6×615)F1代接种L615白血病细胞株建立小鼠白血病模型作为移植受鼠,利用免疫磁珠纯化骨髓CD34+造血干细胞及脾脏CD3+细胞,流式细胞仪分析纯化前后CD34+、CD3+细胞百分比,观察单纯移植CD34+细胞及混合不同数量级CD3+细胞后受鼠生存时间、GVHD、GVL效应,移植后骨髓造血重建细胞来源. 结果纯化CD34+细胞1×10+6移植组100%死于白血病复发;CD34+细胞+纯化CD3+细胞(1×10+7)移植组生存期明显延长,50%死于白血病复发,无GVHD表现;CD34+细胞+CD3+细胞(5×10+7)移植组长期存活,无白血病复发,无GVHD表现;CD34+细胞+CD3+细胞(1×10+8)移植组62.5%死于GVHD,37.5%长期存活;CD34+细胞+CD3+细胞(1.5×10+8)移植组100%死于GVHD.移植后生存时间>60 d的受鼠骨髓造血重建细胞y染色体检出率为100%. 结论移植物中CD3+细胞数量与GVHD和GVL效应密切相关,通过限定移植物中的CD3+淋巴细胞的含量能够保留GVL作用而有效控制GVHD发生.     

非骨髓清除性异基因外周血造血干细胞移植(NST)治疗恶性血液病的初步临床研究

目的　探讨NST治疗恶性血液病的效果及毒性。方法　急性粒细胞白血病未分化型 (AML -M1)、慢性髓细胞白血病 (CML)、骨髓增生异常综合征 (MDS -RA)患者各 1例 ,供体为其HLA配型完全相合的同胞。供体动员方案 :G -CSF 30 0 μg/ 12h× 5d后分离采集外周血干细胞。所获CD34 + 细胞数分别为 6 .36× 10 6/kg、9.72×10 6/kg、6 .6 2× 10 6/kg ;单个核细胞数 (MNC)分别为 14.0× 10 8/kg、10 .47× 10 8/kg、8.5 8× 10 8/kg ;T细胞总数分别为 8.80× 10 8/kg、7.12× 10 8/kg、5 .6 7× 10 8/kg ;CFU -GM数分别为 16 2个 / 2× 10 5MNC、184个 / 2× 10 5MNC、182个 / 2× 10 5MNC。预处理方案 :Fludarabine:30mg/m2 ·d-1× 6d ,Bu :4mg/kg·d-1× 2d ,ALG :12mg/kg·d-1× 4d ,Ara-C :10 0mg/m2 ·d-1× 3d。单用环胞菌素 (CSA)预防移植物抗宿主病 (GVHD)。移植后未用造血生长因子。结果　患者均能顺利完成预处理方案 ,没有严重并发症出现。移植后 10～ 13d造血重建。未发生急性GVHD。随访10 0～ 16 0d ,血常规、骨髓象均正常 ,1例发生肝脏型慢性GVHD。结论　NST能有效治疗恶性血液病 ,方案相关毒性小 ,适用范围广 ,移植相关并发症少 ,造血重建迅速。     

人类白细胞抗原不相合造血干细胞移植治疗白血病的临床研究

目的 :探讨应用人类白细胞抗原 (humanleukocyteantigen ,HLA)不相合供体造血干细胞移植治疗白血病。方法 :总结我所于 2 0 0 0年 7月至 2 0 0 1年 12月进行的 7例HLA不相合造血干细胞移植 ,其中包括 3例慢性髓性白血病、3例急性非淋巴细胞性白血病、1例急性淋巴细胞白血病。干细胞来源 :6例为外周血干细胞 ,1例为骨髓干细胞。预处理方案为改良马利兰 (busulfan ,BU) /环磷酰胺 (cyclophosphamide,CY)或BU/CY +抗胸腺细胞球蛋白 (antithymocyteglobulin ,ATG)。预防急性移植物抗宿主病 (graftversushostdisease,GVHD)采用环孢霉素A及短疗程氨甲喋呤 ,5例患者加用霉酚酸酯 (骁悉 )。结果 :1例为骨髓造血干细胞 ,采集骨髓单个核细胞数 3 .4 1× 10 8kg-1,6例为粒细胞集落刺激因子 (granlocytecolony stimulatingfactor,G CSF)动员后外周血干细胞 ,平均接受8.4 6× 10 8kg-1(4.3 0× 10 8～ 15 .3 5× 10 8kg-1)供者外周血单个核细胞 ,平均 + 13天 (+ 11～ + 16天 )中性粒细胞(absoluteneutrophilcount,ANC)大于 0 .5× 10 9L-1。平均 + 16天 (+ 11～ + 2 3天 )血小板大于 2 0 .0× 10 9L-1。发生急性Ⅰ～Ⅱ度GVHD 3例 (42 .9% ) ,无 1例严重的急性GVHD ,发生慢性广泛性GVHD 2例 (2 8.6% )。中位随访时间 1     

造血干细胞移植治疗儿童白血病的临床研究

【目的】评价造血干细胞移植 (HSCT)治疗儿童白血病的疗效及合并症。【方法】非血缘相关脐血移植 (UD UCBT)治疗儿童白血病 5例 (AML 4例 ,HR ALL 1例 ) ;同胞外周血造血干细胞移植 (allo PBSCT)治疗CML及HR ALL各 1例 ;自体外周血造血干细胞移植 (auto PBSCT)治疗AML 2例。UD UCBT中 4例为HLA 5 / 6相合 ,1例为全相合。输入的脐血 (UCB)平均有核细胞数 (NC)为 6 2 9× 10 7/kg ,CFU GM为 0 17× 10 5/kg ,CD34+ 细胞数为 4 6× 10 5/kg。预处理主要以马利兰 (Bu)、环磷酰胺 (CY)、氟达拉宾 (Flu)和马法兰 (Mel)等组成的方案。【结果】 4例可评价的UD UCBT患儿中 3例完全植入 ,1例未植入者自体造血恢复 ,2例allo PBSCT患儿均完全植入。UCBT后外周血中性粒细胞绝对计数 (ANC)≥ 0 5× 10 9/L的中位时间为 +2 1d ,血小板 (PLT)≥ 2 0× 10 9/L的中位时间为 +40d。 2例allo PBSCT患儿外周血ANC≥ 0 5× 10 9/L的中位时间分别为 +10d和 +12d ,PLT≥ 2 0× 10 9/L的中位时间为 +11d和 +14d。 3例植入的UCBT者 2例分别发生Ⅰ度和Ⅲ度aGVHD。 2例allo PBSCT患儿分别发生Ⅱ度和Ⅲ度aGVHD。随访 2 5个月 ,2例auto PBSCT患儿均复发。allo HSCT 7例中 2例复发 ,2例死于移植合并症 ,3例无病存活至今。【结论】H     

无关供者脐血移植治疗小儿急性白血病

目的　探讨无关供者脐血移植 (UNRUCBT)治疗小儿急性白血病的可行性。方法　用HLA不全相合UNRUCBT治疗小儿急性白血病患儿 6例。供给受者的有核细胞 (3 63～ 15 35 )× 10 7/kg ,CD34 +细胞 (0 2 8～ 1 0 3)×10 7/kg ,粒 -巨噬细胞集落形成单位 (2 12～ 8 32 )× 10 5/kg。移植的预处理方案采用马利兰 +环磷酰胺 +抗胸腺细胞球蛋白方案。结果　 6例患儿白细胞均达到了植入的标准 ,其平均中性粒细胞 >0 5× 10 9/L时间为 19 33d ;5例血小板达到植活标准 ,其平均血小板 >5 0× 10 9/L时间为 5 7 4d。 5例患儿发生急性移植物抗宿主病 (aGVHD) ,其中Ⅰ度aGVHD 1例 ,Ⅱ度aGVHD 3例 ,Ⅳ度aGVHD 1例 ,慢性移植物抗宿主病 (aGVHD) 1例。 1例死于Ⅳ度aGVHD ,1例死于Ⅲ度HC。 4例长期存活的患儿中 ,1例在移植后 12个月出现“供者型”复发 ,经再次化疗获得完全缓解 ;另 3例分别无病存活 2 9,2 2 ,16个月。结论　URUCBT能长期重建受体造血功能     

造血干细胞移植治疗儿童白血病及恶性肿瘤

目的　探讨造血干细胞移植治疗儿童白血病及恶性肿瘤的疗效。方法　采用造血干细胞移植治疗儿童白血病及实体瘤 17例 ,其中ALL 8例 ,AML 4例 ,CML 2例 ,淋巴瘤 1例 ,神经母细胞肿瘤 1例 ,性腺外生殖细胞肿瘤 1例。异基因造血干细胞移植 10例 ,自体造血干细胞移植 7例。结果　获得植入的 9例异基因造血干细胞移植患者造血恢复(WBC >1× 10 9/L)平均时间为 2 1 7d ,自体造血干细胞移植患者造血恢复平均时间为 16d。 8例异基因造血干细胞移植患者均使用了相似的方案 (Cy +TBI +VP16 +MeCCNU) ,均获得植入。在 5 /10异基因骨髓移植长期存活的病例中 ,3例为HLA不相合同胞。结论　HLA不相合异基因造血干细胞移植对于难治性和复发的白血病是一个可以选择的办法     

非血缘造血干细胞移植的临床研究

目的探讨非血缘性(无关供者)异基因造血干细胞移植治疗白血病。方法HLA配型不相合非血缘脐血移植治疗儿童白血病3例(ALL,CR2),无关供者异基因外周血造血干细胞移植治疗成人白血病1例(M6,NR),输入的脐血有核细胞(4.98～6.68)×107.kg-1,CD34+(2.24～4.93)×105.kg-1。输入的外周血的单个核细胞7.04×108.kg-1,CD34+1.08×106.kg-l。预处理主要为:阿糖胞苷,马利兰,环磷酰胺,甲基环已亚硝脲,抗胸腺细胞球蛋白。结果4例患者完全植入,+15～+25天白细胞(WBC)>1.0×109L-1,+35天～+51天血小板(PLT)>20×109L-1。例1移植后+12及+51天出现可疑为急性GVHDI度,例4于+16天出现肝静脉闭塞综合征(轻型)(VOD),+17天出现急性消化道GVHDI度,+30天出现出血性膀胱炎(HC),例2于移植后六个月复发,放弃治疗而死亡。余3例正常生活或工作。结论无关供者或对于HLA不相合的异基因造血干细胞移植是治疗白血病的有效方法,且可以是安全、可行的。     

异基因造血干细胞移植治疗重型再生障碍性贫血的疗效分析

目的:回顾性分析观察异基因造血干细胞移植治疗重型再生障碍性贫血(SAA)的安全性及临床疗效?方法:回顾分析本科自2007年8月~2012年6月接受异基因造血干细胞移植的9例SAA患者的临床资料,其中同胞人类白细胞抗原(HLA)全相合4例,亲缘半相合4例,无关供者全相合1例?均采用含环磷酰胺的预处理方案,移植物抗宿主病(GVHD)的预防:接受同胞全相合移植患者采用短程甲氨蝶呤(MTX)联合环孢素(CSA)方案,其他患者采用短程MTX?CSA?骁悉及舒莱联合方案?回输外周血干细胞中位单个核细胞数和CD34阳性细胞数分别为6.86 × 108个/kg和2.41 × 106个/kg?结果:9例患者全部获得造血重建,中性粒细胞和血小板的中位植活时间分别为17 d和19 d?除1例为自身造血恢复外,8例均为供者造血?1例接受亲缘半相合移植患者在移植后 + 186 d死于肺部感染?8例存活患者中位随访时间1 142(405~1 836)d,均达无病生存?结论:异基因造血干细胞移植治疗SAA安全有效,对于无全相合干细胞来源的SAA患者也可以考虑接受亲缘半相合移植?     

Value of D-Dimers in patients with acute aortic dissection

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.     

Research of combined liver-kidney transplantation model in rats

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.     

安心颗粒对急诊经皮冠状动脉介入术后生活质量影响的研究

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.     

The comparative studies of the influences of Urapidil and Nicardipine on sino-atrial node function, atrio-ventricular node function and hemodynamics

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.     

Expression of OPGmRNA and ODFmRNA in the patients of hip fracture due to osteoporosis

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.     

The clinicopathological and immuohistochemical analysis of solid-pseudopapillary tumor of the pancreas： report of 9 cases

Objective：To investigate the clinical features, pathological characteristics and immunophenotype of solid-pseudopapillary tumor of the pancreas（SPTP）. Methods：Nine surgically treated cases of SPTP were retrospectively reviewed. Hematoxylin and Eosin（HE） staining and immunohistochemical staining were used to analyze all cases, and the general clinical data was collected. Results：Six patients were asymptomatic except for a palpable mass. Two patients complained of vague-epigastric pain. One patient appeared jaundice. The tumor was encapsulated and solid tissues alternately with cystic tissues. Histologically, the histological structure of solid portion was pseudopapillary with a fibrovascular core. Tumor cells were uniform and medium-sized which were arranged in sheets ets or nests or pseudopapillary patterns. Immunohistochemical studies demonstrated that SPTP proved positive in vimentin（9/9 cases）, AAT（9/9 cases）, NSE（9/9 cases）, ACT（7/9 cases）, CK20（2/9 cases）, CgA（1/9 cases）, S-100（3/gcases）, PR（4/gcases）, Syn（3/9 cases） and CD56（5/9cases）, negative in CEA and ER. Conclusion：SPTP is a tumor predominantly occurring in young women frequently without special symptoms. This tumor has various characteristical histological patterns with different immunophenotype.     

Electro-Acupuncture Combined with the Trigger Point Needle-Embedding for Treatment of Primary Trigeminal Neuralgia in 31 Cases

In recent years, the author of this essay has applied electro-acupuncture combined with the trigger point needle-embedding for treatment of primary trigeminal neuralgia in 31 cases, yielding satis- factory results as reported in the following.     

Investigation of Matrix Metalloproteinase -1, 2 and tissue inhibitor of matrix metalloproteinases-1 in Endometriosis

Objective： To explore the role of matrix metalloproteinase-1,2 （MMP-1, MMP-2） and tissue inhibitor of matrix metalloproteinases-1 （TIMP-1） in endometriosis. Methods： The eutopic and ectopic endometria from 40 subjects suffering from endometriosis and regular.endometria from 40 subjects （excluding endometriosis） were collected and examined by in situ hybridization technology and western blot assay. Results： Both expressions of MMP-1 and -2 were stronger in ectopic endometrium and eutopic endometrium than in normal endometrium. On the contrary, the expression of TIMP-1 in ectopic endometrium and eutopic endometrium was lower. The differences were significant （P 〈 0.01 ）. Moreover, there was no relationship among the expressions of MMP-1, 2 and TIMP-1 in ectopic endometrium. Conclusion： The expressions of MMP-1, 2 and TIMP-1 lose balance and lack of periodic changes in ectopic endometrium , which explains the biological invasive behavior of endometriosis. It was suggested-that regulating the balance between the MMPs and TIMP-1 should be an ideal therapeutic target to endometriosis.     

Shi Da-zhuo (史大卓) —An outstanding cardiologist of integrative medicine

Prof. SHI Da-zhuo, Ph.D., male, was born on March 20, 1960. Prof. SHI entered the Ph.D. program in 1990 at the China Academy of Chinese Medical Sciences under the supervision of Prof. CHEN Ke-ji, majoring in the treatment of cardiovascular diseases. After receiving his Ph.D. degree in 1993, Prof. SHI started working at the Cardiovascular Center in Xiyuan Hospital affiliated to China Academy of Chinese Medical sciences.     

Persist in and Carry Forward the Integrative Medical Research——Speech at the 6th National General Congress of Chinese Association of Integrative Medicine by Academician CHEN Zhu,Minister of Ministry of Health

The 6th National General Congress of Chinese Association of Integrative Medicine （CALM） was convened at 19-20, April 2008 in Beijing. Academician CHEN Zhu, the minister of Ministry of Health indicated at the congress that the integration of Chinese and Western medicine is very well in keeping with the situation of our country and the general rule of development in medical science; and as a good integration of Chinese medicine and Western medicine, it is mutually beneficial and advantageous to both of them. Seeing the creativity shown in integrative medical investigation in theoretic and methodological sides, we should and must persist in and develop it.