多西他赛脂肪乳注射液在大鼠体内的药代动力学研究

制备多西他赛脂肪乳注射液,并考察大鼠尾静脉给药后体内的药代动力学行为。采用高压均质法制备多西他赛脂肪乳注射液,将12只Wistar大鼠随机分为多西他赛脂肪乳注射液组和多西他赛注射液组,尾静脉给药剂量均为6 mg/kg,采用HPLC法测定大鼠血中多西他赛的浓度,采用3P97程序计算多西他赛药代动力学参数。多西他赛脂肪乳注射液平均粒径为(221.6±13.4)nm,聚合物分散指数(PDI)为0.092±0.003,Zeta电位为-30.3 mV。多西他赛脂肪乳注射液和多西他赛注射液在大鼠体内的t_1/2(α)分别为(0.072±0.014)和(0.066±0.015)h;t_1/2(β)分别为(0.573±0.253)和(0.432±0.184)h;AUC_{0-12 h}分别为(7.98±1.25)和(6.26±1.83)μg·h/mL。多西他赛脂肪乳注射液与市售多西他赛注射液相比,在大鼠体内具有相似的药代动力学特征,药代动力学过程均符合双室模型。     

生物电阻抗分析法观察乳腺癌患者上肢淋巴水肿治疗效果

目的：研究生物电阻抗分析法观察乳腺癌患者术后上肢淋巴水肿经爱脉朗(Daflon)治疗后的效果。方法：乳腺癌患者术后发生上肢淋巴水肿19例，口服爱脉朗治疗，治疗前后采用多频生物电阻抗分析法测定人体组成成分，计算细胞外液／细胞内液(ECW/ICW)和细胞外液／全身水量(ECW/TBW)比值。结果：治疗后患侧肢体液体含量及机体ECW/ICW和ECW/TBW比值均显著低于治疗前。结论：生物电阻抗分析法能准确观察乳腺癌患者术后上肢淋巴水肿，爱脉朗能明显改善乳腺癌患者术后上肢淋巴水肿。     

唑来膦酸联合化疗治疗非小细胞肺癌骨转移48例

目的 探究为非小细胞肺癌骨转移患者行唑来磷酸联合多西他赛化疗方案予以治疗的临床效果,及对患者生活质量的影响,为该疾病的临床治疗提供参考.方法 择取47例患者参与此次研究,为本组行唑来磷酸联合多西他赛化疗按方案予以治疗.通过视觉模拟评分法(VAS)评定本组患者治疗前、后的疼痛程度,比较本组患者治疗前、后的骨病灶抑制率、肺部原发病灶抑制率、行为状态评分(KPS)、碱性磷酸酶(AKP)水平、血清钙浓度、治疗不良反应,以及通过生活质量评定量表(SF-36)评定患者治疗前后生活质量.结果 经过治疗后,本组患者的VAS评分、AKP水平以及血清钙相比治疗前有显著下降,KPS评分以及SF-36评分相比治疗前有明显上升,治疗后(5.95±1.34)分、躯体功能(1.95±0.40)分、情绪功能(1.88±0.32)分、角色功能(1.92±0.43)分以及社会功能(1.91±0.34)分,均显著优于治疗前相应指标(4.02±1.23)分、(1.61±0.31)分、(1.52±0.23)分、(1.64±0.31)分以及(1.64±0.22),数据通过统计学进行分析后差异具有统计学意义(P<0.05).治疗后骨病灶抑制率为59.57%、肺部原发病灶抑制率为44.68%.结论 唑来磷酸联合多西他赛化疗方案应用于非小细胞肺癌骨转移患者治疗中的临床效果理想,可有效抑制其骨转移及肺癌症状和进展,缓解患者因病所受的疼痛感,降低治疗不良反应发生率,并提升患者的生活治疗,因此该种治疗方案具有推广的价值.     

多西他赛联合塞替派治疗中晚期非小细胞肺癌的临床观察

目的探讨多西他赛联合塞替派治疗中晚期非小细胞肺癌的疗效及不良反应。方法中晚期非小细胞肺癌86例,随机分为两组,应用多西他赛联合塞替派方案(A组)(多西他赛35mg/m2d1,8,塞替派60mg/m2d1,21d为1疗程),多西他赛联合顺铂方案(B组)(多西他赛35mg/m2d1,8,顺铂80mg/m2d1,21d为1疗程)化疗2个疗程,评价其效果。结果 A组和B组治疗效果分别为:两组均无完全缓解(CR),部分缓解(PR)25.58%vs 20.93%,稳定(SD)53.49%vs48.83%,进展(PD)20.93%vs 39.70%。P值均>0.05,差异无统计学意义;最常见不良反应为骨髓抑制、胃肠道反应(恶心,呕吐)、肝脏损害转氨酶升高,手足综合征程度较轻。两组患者不良反应0～Ⅱ°和Ⅲ°～Ⅳ°比较,差异无统计学意义(P>0.05)。结论多西他赛联合塞替派方案治疗中晚期非小细胞肺癌有一定的近期疗效,不良反应可耐受,可以作为经济有效的化疗方案。     

多西他赛联合顺铂治疗晚期乳腺癌的临床观察

目的:观察多西他赛联合顺铂对一线治疗失败的晚期乳腺癌的疗效和不良作用.方法:经病理组织学确诊的晚期乳腺癌34例,采用多西他赛注射剂70mg/m2静滴第1天.每位患者用多西他赛前一天应用地塞米松针10mg静推,应用多西他赛前30分钟再次给予地塞米松针10mg静注和苯海拉明20mg肌注以预防过敏反应和液体潴留综合征.顺铂30mg/m2静脉点滴,第1～4天.化疗前用格拉斯琼镇吐剂.21天为1个周期,2周期评价疗效.结果:可评价疗效34例,CR 2例,PR 15例,SD 10例,PD 7例.有效率(CR PR)50.0%,临床获益率(CR PR SD)79.4%.主要毒副反应是骨髓抑制、消化道反应、脱发等.结论:多西他赛联合顺铂治疗晚期乳腺癌的近期疗效显著,是晚期乳腺癌的有效解救治疗方案.     

多西他赛与顺铂单药化疗同期放疗治疗非手术食管癌的对照研究

目的 比较多西他赛与顺铂单药化疗同期放疗治疗非手术食管癌的疗效及安全性.方法 方便收集2011年1月-2013年2月在该院住院治疗的失去手术治疗机会的原发性食管癌患者70例.根据治疗方法分为顺铂组35例和多西他赛组35例.所有患者均接受相同放疗方案,多西他赛组在放疗同期给予多西他赛治疗;顺铂组患者在放疗同期给予顺铂治疗.比较两组的生存期、 近期疗效及不良反应发生情况.结果 顺铂组生存时间、1年生存率分别为(20.2±3.2)个月、60.0%,多西他赛组分别为(21.0±4.5)个月、57.1%,两组比较差异无统计学意义(P>0.05),多西他赛组的近期有效率为100.0%,明显高于顺铂组的82.9%(P<0.05).结论 多西他赛联合同期放疗对非手术食管癌的有效率较高,毒副作用较轻,值得临床借鉴推广.     

冰帽对预防乳腺癌术后化疗患者脱发的效果分析

目的 探讨佩戴冰帽持续降温对预防乳腺癌患者术后化疗引起脱发的效果.方法 选择化疗方案含有多西他赛的乳腺癌术后化疗患者120例,随机分为A、B、C 3组,各40例.A组于多西他赛输注前30 min将电子冰帽戴在头上,佩戴至化疗药输注结束;B组于多西他赛输注时开始佩戴,至化疗药输注结束摘下;C组于多西他赛输注时开始佩戴电子冰帽,佩戴至化疗药输注结束后2 h.分析3组6个疗程结束后的脱发程度.结果 A组中发生Ⅰ度脱发19例,Ⅱ度脱发15例,Ⅲ脱发6例;B组中发生Ⅰ度脱发22例,Ⅱ度脱发12例,Ⅲ脱发5例;C组中发生Ⅰ度脱发33例,Ⅱ度脱发6例,Ⅲ脱发1例;3组发生0度脱发和Ⅳ度脱发均为0例.3组比较,差异有统计学意义(P<0.05).结论 化疗期间佩戴冰帽可以预防化疗引起脱发,佩戴时间越长,预防化疗引起脱发的效果越显著.     

白花蛇舌草乙醇提取物逆转肺癌细胞化疗耐药的作用研究

摘 要 目的 探讨白花蛇舌草乙醇提取物（EEHDW）在肺癌化疗耐药中的作用及可能的机制。方法 EEHDW作用于多西他赛耐药细胞系A549/DTX后，采用集落形成、Transwell和CCK-8检测处理前后细胞的增殖、侵袭和半数抑制量（IC50）情况，Western blot检测上皮间质转化相关蛋白E-钙黏蛋白（E-cadherin）和波形蛋白（vimentin）的表达，同时分析PI3K/Akt信号通路中磷酸化PI3K（p-PI3K）和磷酸化Akt（p-Akt）蛋白表达变化情况。结果 与亲本A549细胞相比，多西他赛耐药的A549/DTX发生了上皮间质转化（EMT）；与对照组相比，EEHDW（2、4、6mg/mL）能抑制A549/DTX细胞的集落形成[(102±9.23)、(69±4.25)、(68±3.12)比(201±8.18), P<0.05]和侵袭能力[(42±5.58)、(21±3.25)、(22±4.36)比(129±9.23), P<0.05]；Western blot结果显示EEHDW（2mg/mL）能够上调E-cadherin蛋白表达，下调vimentin蛋白表达[(31.35±5.27)比(76.05±7.81)、(82.24±6.80)比(35.04±5.32)，P<0.05]；EEHDW（2mg/mL）处理A549/DTX细胞48h后，细胞对多西他赛的半数抑制量IC50显著降低[(81.36±7.58)比(45.38±6.82) ，P<0.05]；此外，与对照组相比，EEHDW（2mg/mL）能够抑制磷酸化(p)-PI3K[(45.62±6.15)比(22.85±4.29) ，P<0.05]和p-Akt[(43.51±3.18)比(23.25±3.67) ，P<0.05]蛋白的表达水平。结论 EEHDW能够抑制A549/DTX细胞增殖、侵袭，逆转多西他赛诱导的EMT和化疗耐药，其机制可能与PI3K/Akt信号通路有关。     

介入化疗对宫颈癌DNA含量、细胞周期时相的影响

目的 :探讨介入化疗对宫颈癌DNA含量和细胞周期时相的影响。方法 :取正常宫颈组、宫颈癌组介入化疗前和介入化疗后各 2 0例的宫颈组织标本 ,用流式细胞术测定其DNA含量 (DI)和S期细胞比率 (SPF)。结果 :(1)宫颈癌组介入化疗前和介入化疗后的DI分别为 (1.31± 0 .34,1.10± 0 .15 ) ,都明显高于正常宫颈组 (1.0 1± 0 .0 6 )(P <0 .0 1,P <0 .0 5 )。宫颈癌组介入化疗后的DI显著低于介入化疗前 (P <0 .0 5 )。宫颈癌II期与III、IV期间DI无显著性差异 (P >0 .0 5 )。 (2 )宫颈癌组介入化疗前DNA异倍体为 13例 ,介入化疗后为 6例 ,两者有显著性差异 (P <0 .0 5 )。 (3)宫颈癌组介入化疗前的SPF(2 4 .93± 9.4 6 % )、介入化疗后的SPF(14 .0 3± 6 .5 9% )均较正常宫颈组的SPF高 (6 .99± 4 .0 7% ,P <0 .0 0 1)。宫颈癌组介入化疗后的SPF低于介入化疗前 (P <0 .0 0 1)。III、IV期的SPF显著高于II期的SPF(P <0 .0 5 )。结论 :介入化疗能抑制宫颈癌组织DNA的复制、降低宫颈癌组织的S期细胞比率 ,抑制肿瘤细胞的增殖     

多西他赛联合卡铂治疗晚期非小细胞肺癌的临床研究

目的 观察国产多西他赛联合卡铂治疗晚期非小细胞肺癌的临床疗效和毒副反应.方法 53例晚期非小细胞肺癌患者均经细胞学或组织学证实,所有患者均进行多西他赛联合卡铂方案化疗,其中多西他赛75 mg/m2静脉滴注,第1天;卡铂AUC=5 mg/(ml·min),静脉滴注,第1天;21天为1周期,化疗两周期评价一次疗效.每例患者至少接受二个疗程化疗.结果全组53例患者均可评价疗效,完全缓解(CR)2例,部分缓解(PR)22例,稳定(SD)20例,疾病进展(PD)9例,总有效率为45.3%.其中初治患者28例,CR+PR 16例,有效率57.1﹪;复治25例,PR 8例,有效率32.0%.毒性反应主要有骨髓抑制和胃肠道反应,疲乏,脱发,口腔粘膜炎.结论多西他赛联合卡铂方案是治疗晚期非小细胞肺癌较为理想的方案之一.     

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.     

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.     

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.