急性髓系白血病患者 FLT3-ITD 基因突变检测的意义

目的：探讨对急性髓系白血病（ AML ）患者行FLT3-ITD基因突变检测的临床意义。方法选取首次确诊的AML患者50例,对患者进行常规FAB分型及R显带核型分析,并抽取患者骨髓进行FLT3-ITD突变检测,根据其突变发生与否将患者分为阳性组和阴性组。患者接受诱导治疗。比较两组患者的年龄分布、性别比例、染色体核型、白细胞计数（ WBC ）、骨髓原始细胞比例、外周血血红蛋白浓度、血小板计数等一般临床参数和诱导治疗临床结局、患者生存情况。结果50例患者中共检出FLT3-ITD突变阳性（阳性组）10例,阴性患者（阴性组）40例。两组患者间一般临床参数中除了WBC、骨髓原始细胞2项指标差异有统计学意义（P＜0.05）外,其余指标差异均无统计学意义（P＞0.05）。阴性组患者完全缓解（CR）率高于阳性组,复发率低于阳性组,差异均有统计学意义（P＜0.05）。阳性组患者的无病生存率和总体生存率均低于阴性组,差异均有统计学意义（P＜0.05）。结论 FLT3-ITD突变阳性AML患者CR率低,复发率高,预后差,早期检测FLT3-ITD突变发生情况具有重要临床意义。     

FLT3-1TD、NPM1和C-KIT基因突变在成人急性髓系白血病中的表达及临床意义

目的探讨成人急性髓系白血病患者中FLT3-ITD、NPMI、C—kit基因突变表达及临床意义。方法采用PCR技术检测50例成人急性髓系白血病患者治疗前后FLT3-ITD、NPM1、C—kit表达,比较分析FLT3-ITD、NPMI、C—kit突变与临床资料、细胞遗传学的关系及预后影响。结果50例急性髓系白血病中NPM1突变检出率占38％,在正常核型占61．9％,显著高于在异常核型（P〈0．05）;FLT3-ITD突变检出率32％,正常核型占38．1％,与在异常核型相比无显著性差异（P〉0．05）;C—kit突变检出率10％,核型为t（8;21）占80％、,FLT3-ITD、NPM1突变初诊时WBC、LDH、α-HBDH显著高于无突变患者（P〈0．05）;在NPM1突变患者中伴FLT3＂ITD突变占68．42％,显著高于在无NPM1突变患者中伴FLT3-ITD突变占的9．68％（P〈0．05）;单纯NPMI突变CR率i00％,显著高于无三基因突变的患者54．16％（P〈0．05）,FLT3-ITD、NPMI突变CR率46．15％,显著低于单纯NPM1突变CR率100％（P〈0．05）。CR的患者FLT3-ITD、NPM1、C—kit突变均转阴,复发患者再次检出突变早于骨髓复发。结论FLT3-ITD、NPMI及C—kit基因突变在急性髓系白血病上有特殊的分布,并且与白细胞数、骨髓原始细胞比例、血小板数、LDH、α-HBDH密切相关,三基因突变可作为判断预后及监测微小残留病灶的指标．     

急性早幼粒细胞白血病不同PML/RARa亚型的临床特点分析

目的 分析急性早幼粒细胞白血病(APL)患者3种早幼粒细胞白血病-维A酸受体α(PML/RARa)基因亚型的临床特点.方法 收集2014年6月至2017年7月该院血液内科收治PML-RARa分型明确的49例APL患者的临床资料,比较不同类型PML/RARa亚型的临床特点.结果 L、S、V3种亚型分别占75.51％、22.45％、2.04％.早期死亡(ED)6例,占12.24％;L型ED发生率为8.11％,S型为27.27％.发生FLT3突变共9例,占18.36％;其中FLT3-ITD 7例,占14.28％,L型8.11％,S型36.37％,差异有统计学意义(x2 =5.43,P＜0.05);L型纤维蛋白原(Flb)水平为1.90(1.11,2.49)g/L,S型Flb水平为0.91(0.71,1.68)g/L,差异有统计学意义(Z=-2.680,P=0.007);L型患者CD34阳性率为16.66％,S型为62.50％,差异有统计学意义(x2 =6.84,P＜0.05);L型患者CD56阳性率为6.66％,S型为37.50％,差异有统计学意义(x2=5.25,P＜0.05);L型患者的1年及2年生存率均为91.9％,S型患者均为72.7％,L型患者生存率高于S型患者,但差异无统计学意义(x2 =2.888,P=0.089).结论 同等危险度分层下,S型患者的生存率低于L型患者,其ED发生率、FLT3-ITD突变率、CD34阳性率及CD56阳性率均高于L型患者,Flb水低于L型患者,S型患者的预后与L型相比可能欠佳.     

FLT3及C-kit突变在急性髓系白血病的临床意义

目的探讨FLT3及C-kit基因突变在急性髓细胞白血病(AML)中的临床意义。方法回顾性分析南方医院2010年1月—2013年12月期间初诊AML患者的临床资料,PCR分析FLT3及C-kit基因突变情况。结果248例初诊AML患者中,FLT3-ITD突变率为16.9%,TKD突变率为3.2%,C-kit8号外显子突变率为1%,17号外显子突变率为5.2%;FLT3-ITD突变更倾向发生于正常染色体核型的AML患者;FLT3突变阳性组及C-kit突变阳性组患者的外周血白细胞数高于基因突变阴性组,染色体核型正常患者的无病生存时间较阴性组缩短(P<0.05)。但是对血红蛋白、血小板及完全缓解率(CR率)并无影响(P>0.05)。结论 FLT3及C-kit突变的AML患者有较差的临床预后。     

初诊急性髓系白血病患者FLT3-ITD和NPM1基因联合突变与临床特征的关系

目的探讨初发急性髓系白血病（AML）患者中FMS样酪氨酸激酶3-基因内部串联重复（FLT3-ITD）和核仁磷酸蛋白1（NPM1）基因突变的发生频率,并进一步分析其与患者临床特征的关系。方法收集44例临床初诊为AML的成人患者骨髓标本,通过基因组DNA-PCR技术对FLT3-ITD和NPM1基因突变进行检测。结果44例患者共检测到FLT3-ITD突变10例,检出率22.7%。FLT3-ITD突变阳性的10例患者和无突变者初诊WBC中位数分别为（98.5±22.5）×109/L和（42.9±12.4）×109/L,两者相比具有统计学差异（P＜0.05）。44例患者共检测到NPM1突变14例,检出率31.8%。大部分突变患者,染色体核型正常。结论FLT3-ITD和NPM1基因突变是AML患者中常见的分子生物学异常,对患者的临床和预后有影响。     

三氧化二砷联合全反式维甲酸诱导治疗初治急性早幼粒细胞白血病患者疗效的影响因素分析

目的：观察三氧化二砷（ATO）联合全反式维甲酸(ATRA)诱导治疗初治急性早幼粒细胞白血病（APL）的疗效,分析联合诱导治疗下影响初治APL疗效的预后因素。方法：将联合应用ATO和ATRA治疗的107例初治APL患者,根据危险因素分层、形态学差异、融合基因和染色体的不同分别分为高危组、中危组、低危组,粗颗粒组(M3a)、细颗粒组(M3b),融合基因长型组（L+）组、融合基因短型（S +）组,典型核型组、附加核型组,比较治疗过程中各组早期死亡率及治疗后各组患者血液学完全缓解(CR)率及达CR时间,确定影响疗效的预后因素。结果：①107例患者,10例早期死亡,早期病死率为9.35%,最常见不良反应为凝血功能异常及白细胞增多。②高危组达CR时间、CR率和早期病死率与中危和低危组比较差异有显著性（P＜0.05）,而低危与中危组比较差异无显著性（P>0.05）;M3b组较M3a组达CR时间明显延长,但两者CR率差异无显著性（P>0.05）;融合基因（L＋） 组CR率高于融合基因（S＋）组,达CR时间短于后者（P＜0.05）;典型核型组和附加核型组CR率、达CR时间差异均无显著性（P>0.05）。结论： ATO和ATRA联合诱导治疗,初诊APL患者白细胞计数、形态学分型和分子生物学分型可能是影响CR的因素,而附加染色体异常对短期CR无明显影响。     

NPM1、CEBPA、FLT3-ITD及c-kit基因突变在正常染色体核型的急性髓细胞白血病患者中的临床意义

目的:分析NPM1、CEBPA、FLT3-ITD及c-kit基因突变在正常染色体核型的急性髓细胞白血病(CN-AML)患者中应用的临床意义。方法:以2016年1月-2017年6月本院收治的100例急性髓细胞白血病患者作为研究对象,利用染色体核型分析G显带方法与基因检测PCR法进行NPM1、CEBPA、FLT3-ITD及c-kit基因突变分析。分析以上四种基因突变的发生率,比较突变型和野生型患者的临床特征、总生存率及累积复发率。结果:NPM1、CEBPA、FLT3-ITD及c-kit基因突变的发生率分别为22.0%、22.0%、13.0%、5.0%;NPM1突变型患者的WBC明显高于野生型,差异有统计学意义(P0.05);CEBPA突变型患者的完全缓解率明显高于野生型,差异有统计学意义(P0.05);FLT3-ITD突变型患者PB和BM明显高于野生型,PLT和完全缓解率明显低于野生型,差异均有统计学意义(P0.05);c-kit突变型患者PLT明显低于野生型,PB和BM明显高于野生型,差异均有统计学意义(P0.05);NPM1突变型总生存率明显高于野生型,CEBPA突变型总生存率明显高于野生型,累积复发率明显低于野生型,差异均有统计学意义(P0.05)。结论:急性髓细胞白血病存在一定比例的基因突变,NPM1、CEBPA突变率相对较高,FLT3-ITD及c-kit基因突变患者的PLT较低,BM原始细胞比例较高,且NPM1、CEBPA突变能够评估预后,具有一定的临床研究意义。     

PCR结合DNA测序技术检测急性白血病FLT3与NPM1基因突变及其临床意义

目的 研究成人急性白血病(AL)患者FMS样酪氨酸激酶3(FLT3)及核仁磷酸蛋白(NPM1)基因突变发生情况及临床意义.方法 采用PCR结合DNA测序技术分析65例初诊急性白血病(AL)患者骨髓单个核细胞中FLT3及NPM1基因突变发生情况.结果 在59例急性髓系白血病(AML)患者中检测到FLT3-ITD突变阳性10例(16.9%),NPM1突变阳性15例(25.4%),其中3例同时存在FLT3-ITD突变及NPM1基因突变;而在6例急性淋巴细胞白血病(ALL)患者中均未检测到FLT3-ITD突变或NPM1基因突变.两种突变均与初诊时中位WBC数、染色体正常核型比例及伴有特异性融合基因患者比例有相关关系(P＜0.05).FLT3-ITD+AML患者初诊时骨髓原始细胞比例高(P＜0.05),单纯NPM1+AML患者初诊时表现为BPC较高(P＜0.05)、免疫表型CD34阳性患者比例低(P＜0.05);FLT3-ITD突变阳性者化疗后有低缓解率趋势.结论 FLT3-ITD突变和NPM1基因突变是AML患者常见的基因突变类型.对初诊时高白细胞计数、血小板计数不低、骨髓原始细胞比例高、CD34阴性表型和正常核型的AML患者检测FLT3-ITD突变和NPM1突变,有利于临床判断预后和指导治疗.     

FLT3-ITD 突变的急性髓系白血病免疫表型 及临床特征分析

目的 讨论FLT3-ITD 突变的急性髓系白血病（AML）的免疫表型及临床特征。方法 回顾性 分析2015 年6 月—2017 年6 月中国医科大学附属第四医院收治的FLT3-ITD+ 及FLT3-ITD- AML 组患者的 免疫表型、临床资料,并对两组患者化疗后临床结局及生存状况进行比较。结果 FLT3-ITD+ AML 组患者 CD56、CD33、CD11b 及CD7 表达高于FLT3-ITD- AML 组（P <0.05）,而CD34、CD117 表达低于FLT3- ITD- AML 组（P <0.05）。与FLT3-ITD- AML 组患者比较,FLT3-ITD+ AML 组患者外周血白细胞计数及骨 髓原始细胞比例升高（P <0.05）,而血红蛋白及血小板计数比较,差异无统计学意义（P >0.05）;FLT-ITD- AML 组患者总反应率高于FLT3-ITD+ AML 组（P <0.05）;FLT3-ITD- AML 组患者无病生存率和总生存率 高于FLT3-ITD+ AML 组（P <0.05）。FLT3-ITD+ AML 组患者完全缓解患者CD56、CD34、CD11b、CD7、 CD33 及CD117 的表达水平低于未缓解患者（P <0.05）。结论 FLT3-ITD+ AML 患者白血病细胞抗原表达 紊乱,外周血白细胞及骨髓原始细胞高,完全缓解率低,预后差,是AML 预后不良因素。AML 患者早期检测 FLT3-ITD 突变及免疫分型对于指导治疗、判断预后具有重要临床意义。     

急性髓细胞白血病FLT3-ITD基因突变与细胞遗传学的关系

目的探讨急性髓细胞白血病（AML）FLT3-ITD基因突变与细胞遗传学关系.方法采用PCR-DHPLC方法检测60例初治AML患者骨髓单个核细胞FLT3-ITD突变;应用G显带技术进行核型分析.结果 60例初发AML中,FLT3-ITD突变阳性率为21.67%（13/60）;10例对照组均未检测到该突变;不同预后核型组FLT3-ITD突变阳性率不同,预后中等核型组突变率较高40.0%（6/15）,预后中等核型组FLT3-ITD突变阳性者外周血白细胞数、骨髓白血病细胞比例高于预后好核型组及预后差核型组（P〈0.01）.结论 FLT3-ITD突变在AML中多发生于预后中等核型组,而且与预后不良相关;预后中等核型组FLT3-ITD突变阳性者具有外周血高白细胞、骨髓白血病细胞比例高的临床特点.FLT3-ITD突变检测在一定程度上可以弥补细胞遗传学的不足,有可能成为AML常规检测项目之一,有助于白血病的诊断及预后判断.     

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.