无血缘关系供者异基因外周血干细胞移植治疗急、慢性白血病49例

目的 观察无血缘关系供者外周血干细胞移植治疗急、慢性白血病的疗效.方法 自2005年1月至2009年10月本科行无血缘关系供者造血干细胞移植治疗急、慢性白血病患者49例,供、受者之间人类白细胞抗原(HLA)配型全相合43例,HLA 1个位点不合6例(其中,A位点不合2例,B位点不合1例,CW位点不合2例,DQ位点不合1例).预处理方案环磷酰胺(CY)+全身放疗(TBI)方案28例、BU/CY方案21例.采用环孢菌素A(CSA)+骁悉+甲氨喋呤(MTX)+抗胸腺细胞球蛋白(ATG)预防性控制移植物抗宿主病.结果 移植后10～23 d(中位时间14.8 d)中性粒细胞大于0.5×109/L;移植后13～27 d(中位时间18.6 d),血小板大于20×109/L.14例(HLA 1个位点不合者2例)发生Ⅱ度急性移植物抗宿主病(aGVHD),予甲强龙治疗后控制,28例发生慢性移植物抗宿主病(cGVHD),局限型14例,广泛型14例;无1例发生肝静脉闭塞病(VOD)及巨细胞病毒感染;移植相关毒副作用方面CY+TBI方案与BU/CY方案差异无统计学意义;随访5～63个月,41例患者无病生存,8例死于本病复发和移植并发症;21例慢性粒细胞白血病bcr/abl融合基因检测转阴.结论 无血缘关系供者外周血干细胞移植是一种有效的血液肿瘤治疗方法.     

异基因造血干细胞移植治疗白血病12例临床观察

目的 探讨异基因造血干细胞移植(Allo-HSCT)治疗白血病的疗效.方法 选择2007年4月至2009年4月进行异基因造血干细胞移植的患者12例,其中急性淋巴细胞白血病(ALL)2例,急性髓系白血病(AML)4例,慢性粒细胞白血病6例.预处理方案均为BU/CY,采用以CsA、MMF、ATG加短程MTX常规预防移植物抗宿主病,非亲缘移植加用抗胸腺细胞球蛋白(ATG).结果 12例患者移植后均造血重建,发生急性移植物抗宿主病(aGVHD)1例,慢性移植物抗宿主病(cGVHD)2例.移植后100d内移植相关死亡率(TRM)8.3%(1/12),死于aGVHD、感染;移植后100d至2年内TRM为16.7%(2/12),分别死于cGVHD、感染及白血病复发.其余9例无病生存1～24个月,DFS为75%(9/12).结论 异基因外周血干细胞移植是目前惟一可能治愈白血病的方法,值得推广和进一步总结.     

异基因造血干细胞移植治疗骨髓增生异常综合征8例疗效分析

目的 观察异基因造血干细胞移植(allo-HSCT)治疗骨髓增生异常综合征(MDS)的疗效及安全性.方法 对8例MDS患者进行异基因造血干细胞移植,其中同胞全相合供者4例,亲缘间单倍型供者4例.预处理方案为改良BU/CY 4例,地西他滨桥接BU/CY 2例,FLU-IDA/FLU-BU 1例,FLU-BU/CY 1例,同胞全相合移植采集供者外周血造血干细胞,移植物抗宿主病(GVHD)预防给予环孢素A(CSA)加短程甲氨蝶呤(MTX);血缘单倍型移植采集骨髓和外周血造血干细胞,GVHD预防采用CSA、短程MTX及吗替麦考酚酯(MMF),预处理期间加用抗胸腺细胞球蛋白(ATG).随访时间1～13个月.结果 8例患者全部完成造血重建,顺利出仓.粒系植入时间为11.2 d,巨系植入时间为15.8 d,经STR-PCR检测均为完全供者型.Ⅰ～Ⅱ度急性移植物抗宿主病(aGVHD)3例,因自行停用抗排异药物导致Ⅳ度aGVHD并于移植后4个月死亡1例.慢性移植物抗宿主病(cGVHD)2例;移植后复发1例,死亡1例,存活6例.结论 allo-HSCT治疗MDS安全有效,对中高危MDS可能是唯一有效的治疗方法,并宜尽早进行.     

Rh阴性血型同胞间半相合造血干细胞移植治疗慢性粒细胞白血病临床研究

目的 总结国内首例Rh阴性血型同胞间半相合造血干细胞移植经验.方法 对1例53岁慢性粒细胞白血病慢性期女性患者实施同胞间半相合造血干细胞移植(外周血干细胞加骨髓干细胞混合移植),观察造血重建及移植相关并发症.结果 患者ANC＞0.5×109/L,PLT＞20×109/L的时间分别为 15d, 18d;染色体检查提示有XY染色体; 39d内未观察到急性移植物抗宿主病、肝静脉闭塞病、肝肾功能损伤等移植并发症.结论 半相合造血干细胞移植可解决供者来源困难,是治疗慢性粒细胞白血病的有效手段.     

非血缘供者异基因外周血造血干细胞移植治疗急慢性白血病37例疗效分析

目的 探讨非血缘供者异基因外周血造血干细胞移植治疗白血病的疗效、造血重建、并发症及长期生存情况.方法 采用非血缘人类白细胞抗原(HLA)配型相合的外周血造血干细胞对37例急慢性白血病患者进行移植.预处理方案为白消安(马利兰)、环磷酰胺联合阿糖胞苷(BU/CY/Ara-c)或环磷酰胺联合全身放疗及阿糖胞苷(CY/TBI/Ara-c).急性移植物抗宿主病(aGVHD)预防措施:采用环孢素A(CsA)、甲氨蝶呤(MTX)、抗胸腺细胞球蛋白(ATG)、霉酚酸酯(MMF)方案.输注非血缘供者异基因外周血造血干细胞的有核细胞中位数为9.42(4.33~16.00)×108/kg(受者体质量),CD+34细胞中位数为6.76(1.06~20.00)×106/kg(受者体质量).结果 35例获造血重建,经血型、性染色体、DNA多态性监测证实植活,2例植入失败.中性粒细胞计数＞0.5×109/L的时间为10~26 d,中位时间为15.8 d;血小板计数＞20×109/L的时间为10~77 d,中位时间为19.6 d.Ⅰ~Ⅱ度aGVHD发生率为32%(12/37),Ⅲ度aGVHD发生率为5%(2/37),无Ⅳ度aGVHD发生;cGVHD发生率为24%(9/37).随访1.5~90.0个月,30例存活,7例死亡,其中2例因植入失败死亡.结论 非血缘供者异基因外周血造血干细胞移植是治疗急慢性白血病安全有效的方法,可使大部分白血病患者长期无病存活.     

改良BU/CY预处理方案行同胞相合异基因外周造血干细胞移植治疗骨髓增生异常综合征

目的探讨改良BU/CY预处理方案行同胞相合异基因外周血造血干细胞移植(allo-PBSCT)治疗骨髓增生异常综合征(MDS)的疗效。方法收集2009年1月至2010年12月,哈尔滨血液病肿瘤研究所5例MDS进行allo-PBSCT患者。预处理方案为改良BU/CY;预防移植物抗宿主病(GVHD)采用环孢素A/甲氨蝶呤/吗替麦考酚酯(CSA/MTX/MMF)。结果 5例患者均获得移植,中性粒细胞(ANC)≥0.5×109/L的中位时间移植后12.4d(9～14d),血小板(PLT)≥20×109/L中位时间移植后13.25d(10～23d),2例出现Ⅱ度急性移植物抗宿主病(aGHVD),2例出现局限型慢性移植物抗宿主病(cGVHD),3例发生Ⅱ度口腔溃疡,发热4例,其中1例败血症,1例合并肺部感染;2例发生巨细胞病毒(CMV)血症,出血性膀胱炎(HC)2例,1例出现纯红再生性障碍性贫血;中位随访时间12.8个月(8～22个月),1例骨髓增生异常综合征-环形铁粒幼性难治性贫血(MDS-RAS)移植后7个月复发后合并肺部感染死亡,无病存活4例。结论改良BU/CY方案用于MDS移植预处理疗效较好,不良反应可以耐受,安全性好。     

1个位点不相合的非血缘关系外周血造血干细胞移植治疗慢性粒细胞性白血病

目的 观察1个位点不合的非血缘关系外周血造血干细胞移植 (URD-PBSCT) 治疗慢性粒细胞性白血病的疗效及其并发症的防治.方法 采用HLA配型1个位点不相合的非血缘关系外周血造血干细胞移植治疗慢性粒细胞性白血病 1 例.预处理方案为氟达拉滨 白舒菲 抗胸腺细胞球蛋白 (A TG);输入非血缘关系供体单个核细胞数 (MNCs)为5.60×108/kg,CD34 细胞为4.8×lO6/kg;采用霉酚酸酯(MMF)联合环孢素A(CsA)和甲氨蝶呤(MTX)方案,预防急性移植物抗宿主病(aGVHD).结果 患者 25 d造血重建,无aGVHD.结论 MM F联合CsA和短程MTX可用于预防无关供体移植aGVHD预防的发生.     

异基因造血干细胞移植后重度肠道急性移植物抗宿主病的临床分析

目的 探讨异基因造血干细胞移植(Allo-HSCT)后重症肠道急性移植物抗宿主病(aGVHD)的发生情况及预后.方法 2例慢性粒细胞白血病(慢性期)患者接受异基因造血干细胞移植,预处理方案为BU/CY、GIAC方案,以CsA、MMF、ATG加短程MTX预防aGVHD.结果 2例分别于移植后21、40d并发重度肠炎,诊断为肠道aGVHD,予以糖皮质激素为主的综合治疗包括FK506、抗CD25单克隆抗体后缓解.结论 重度肠道aGVHD是异基因造血干细胞移植后常见的最严重并发症之一,有效治疗直接关系到疾病的预后.     

异基因外周血干细胞移植治疗白血病5例报告

目的观察异基因外周血干细胞移植(PBSCT)治疗白血病(Leukemia)的疗效与副作用。方法所选供者均为HLA-A、B、DR位点与患者完全相合的同胞兄弟姐妹。供者经250μg/kg rhG-CSF动员5 d后,单采外周血干细胞1~2次。5例白血病病人经过改良BU/CY预处理方案,输入单个核细胞6.77×108/Kg±1.63×108/kg(5×108/kg~8.67×108/kg),其中CD34+为13.88×106/kg±8.15×106/kg(5.3×106/kg~24.23×106/kg),用MTX+CSA+MMF预防急性移植物抗宿主病(aGVHD)。结果移植-2 d~+2 d WBC降至最低,+11 d~+20 d中性粒细胞>0.5×109/L,+11 d~+55 d血小板>50×109/L。+28 d复查骨髓显示造血恢复、STR位点的DNA检查显示供者细胞生长。随访1年~2年,其中2例出现aGVHD、3例出现cGVHD、2例出现感染、1例出现CNSL,最后骨髓复发死亡。结论采用改良Bu/Cy方案和用MTX+CSA+MMF预防急性移植物抗宿主病(aGVHD)方案进行PBSCT治疗白血病是一种安全、可靠的治疗方法。     

以FCA预处理的造血干细胞移植治疗SAA的临床研究

目的 探讨以氟达拉滨(Flu)、低剂量环磷酰胺(CTX)和抗胸腺细胞球蛋白(ATG)为预处理的FCA方案异基因造血干细胞移植治疗重型再生障碍性贫血(SAA)的疗效及安全性.方法 用FCA预处理方案预处理移植治疗SAA-Ⅰ型和SAA -Ⅱ型患者各2例,其中同胞供者人类白细胞抗原(HLA)低分辨配型(6/6位点)全相合的骨髓联合外周血造血干细胞移植3例、非血缘关系高分辨HLA配型(10/10位点)全相合的外周血造血干细胞移植1例.同胞供者的预处理方案:Flu 30 mg·m-2d-1×5 d,CTX 50～60 mg· kg-1d-1×5 d,ATG 3 mg·kg-1d-1×3 d.非血缘关系的预处理方案:CTX 20 mg· kg-1d-1×2 d,ATG 5 mg· kg-1d-1 ×3 d,Flu 30 mg· m-2d-1 ×4 d.移植物抗宿主病(GVHD)的预防:均采用低剂量环孢素A(CsA)联合低剂量短程甲氨蝶呤(MTX),非血缘关系移植加用霉酚酸酯(MMF)0.5 g bid,+1 d～+28 d.观察移植并发症、输血量、造血重建、嵌合体和生存状态.结果 4例患者均获得造血干细胞的成功植入,移植后中性粒细胞绝对值(ANC)＞0.5×109/L的时间为+10 d～+15 d,血小板(PLT) ＞20× 109/L的时间为+10 d ～ +20 d,移植后输注红细胞3～6 U,血小板4～10 U,随访7～42个月,完全供者嵌合体,血液学完全缓解;患者1出现广泛型慢性移植物抗宿主病(cGVHD),死于多脏器功能衰竭,其余3例无病生存,其中非血缘关系移植的患者4发生轻度局限型cGVHD和巨细胞病毒血症,经过治疗很快控制.结论 Flu、低剂量CTX和ATG的FCA预处理方案的异基因造血干细胞移植治疗SAA的疗效肯定,患者耐受性好,值得推广.     

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.     

BLOOD PRESSURE CHANGE WITH AGE IN SALT-SENSITIVE TEENAGERS

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.     

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.     

Dynamic Changes in Serum Estradiol and Progesterone levels in Patients of Premenstrual Syndrome with Adverse Flow of Liver-qi

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.     

Real-time Three-dimensional Echocardiography in Assessment of Left Ventricular and Right Ventricular Volumes

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.     

SCREENING FOR A 21-CHROMOSOME ABNORMALITY IN PREIMPLANTED EMBRYOS OF ELDERLY WOMEN

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.     

Scientific principles and rigorous processes should be followed in developing clinical guidelines for therapeutic interventions of integrative medicine

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.