盐酸贝那普利片及活性代谢物在中国健康受试者中的生物等效性研究

目的 评价空腹及餐后状态下单次口服盐酸贝那普利片受试和参比制剂的生物等效性。方法 将志愿者按照1:1的比例分配至T-R(受试制剂-参比制剂)和R-T(参比制剂-受试制剂)序列组;采用单中心、随机、开放、两周期、双序列、自身交叉、单次给药(空腹、餐后)的试验方法设计;采用高效液相-色谱串联质谱法测定血药浓度;使用WinNonlin软件的非房室模型对贝那普利主要药代动力学参数C_max、AUC_0-t、AUC_0-∞进行分析;T_max采用非参数秩和检验。结果 空腹组受试制剂和参比制剂贝那普利的主要药代动力学参数如下：C_max分别为(207.86±70.77)ng·mL^-1和(205.20±70.37)ng·mL^-1;AUC_0-t分别为(168.91±36.03)h×ng·mL^-1和(170.23±38.37)h×ng·mL^-1;AUC_0-∞分别为(171.0...     

泮托拉唑钠肠溶片的生物等效性研究

目的 研究泮托拉唑钠肠溶片在中国健康受试者人体药物代谢动力学和生物等效性。方法 空腹和餐后组分别纳入36、42例受试者,每周期随机交叉单次空腹或餐后口服受试或参比制剂40mg,用UPLC-MS/MS法测定人血浆中泮托拉唑浓度,Phoenix WinNonlin8.2统计软件计算药代动力学参数,分析两种制剂的生物等效性。结果 空腹状态下口服泮托拉唑受试制剂和参比制剂的C_max分别为(3295.143±1187.421)、(3600.662±1598.281)ng/mL;T_max分别为3.00(1.50,4.50)、3.50(1.50,5.53)h; AUC_0-t分别为(13148.4±11834.9)、(13400.2±12421.9)ng·h/mL;AUC_0-∞分别为(13877.3±13820.2)、(14990.7±15111.0)ng·h/mL。餐后状态下口服泮托拉唑受试制剂和参比制剂的C_max分别为(3146.162±1045.245)、(3497.986±1176.9...     

复方磺胺甲噁唑人体药动学与生物等效性研究

目的 研究单次空腹口服复方磺胺甲噁唑片在健康受试者体内的人体药代动力学特征和生物等效性。方法 试验采用单中心、随机、开放、单剂量、两制剂、两周期、两序列交叉设计,24例受试者分别空腹口服复方磺胺甲噁唑受试制剂T或参比制剂R。采用超高效液相色谱-串联质谱(UPLC-MS/MS)检测血浆中的磺胺甲噁唑和甲氧苄啶的血药浓度,用Phoenix WinNonlin 8.2软件计算药动学参数,评价两制剂生物等效性。结果 空腹试验受试制剂T和参比制剂R的磺胺甲噁唑C_max、AUC_0-t、AUC_0-∞分别为(27.340±3.400)和(28.042±3.527)μg/mL、(375.2±38.7)和(371.5±35.4)h·μg/mL、(390.0±42.9)和(386.7±41.0)h·μg/mL;甲氧苄啶C_max、AUC_0-t、AUC_0-∞分别为(0.845±0.198)和(0.838±0.144)μg/mL、(8.7±1.3)和(8.2±1.5)h·μg/mL、...     

阿那曲唑片在中国健康绝经期女性志愿者的人体生物等效性研究

  目的  评价在空腹和餐后条件下健康绝经期女性单次口服阿那曲唑受试制剂与参比制剂的生物等效性。  方法  采用开放、随机、双周期、自身交叉试验设计,各纳入24例健康绝经后期女性志愿者,分别在空腹和餐后服用1 mg阿那曲唑受试制剂和参比制剂后,采用高效液相色谱-串联质谱(LC-MS/MS)法测定阿那曲唑的血药浓度。使用Phoenix WinNonlin 6.3版中的非房室模型分析,计算药代动力学参数并评价两种阿那曲唑空腹及餐后服用的生物等效性。  结果  在空腹和餐后条件下健康绝经后期女性志愿者口服受试制剂和参比制剂后的主要药代动力学参数(AUC_0-∞、AUC_0-t、C_max)的几何均数比值90%置信区间均在80.00%~125.00%的范围内。餐后给药与空腹给药相比,t_max延长,C_max降低,而AUC和t_1/2基本一致。  结论  在空腹和餐后条件下阿那曲唑受试制剂与参比制剂具有生物等效性。     

法米替尼治疗晚期实体瘤患者的药代动力学及安全性

目的：研究法米替尼15、20、25 mg剂量组在晚期实体瘤患者的药代动力学特征和安全性。方法：32例晚期或转移的实体瘤患者接受15、20、25 mg/d治疗,比较每个剂量组单次给药和多次给药后原型药物法米替尼及代谢物SHR116637的达峰时间(T_max)、血药峰浓度(C_max)等相关药代动力学的参数变化,观察治疗期间法米替尼在实体瘤患者中的不良事件/严重不良事件的发生率。结果：各剂量组单次给药后,血浆中法米替尼和代谢物SHR116637在6 h达峰,低、中、高剂量组t_1/2分别为(73.6±12.3)、(75.8±17.0)、(65.8±23.8)h;代谢物SHR116637的体内暴露量AUC_0-24、AUC_0-t和AUC_0-∞均随剂量增加而增加。多次给药后血浆中法米替尼及代谢物SHR116637 T_max与单次给药相比略有延迟。多次给药后法米替尼和代谢物SHR116637均有一定程度的蓄积,但以代谢物SHR116637中15 mg...     

盐酸左氧氟沙星胶囊人体药物动力学与生物利用度研究

目的: 研究盐酸左氧氟沙星胶囊健康人体的药物动力学与生物利用度。方法: 高效液相色谱(HPLC)法测定20名健康受试者单剂量口服两种盐酸左氧氟沙星胶囊(受试制剂和参比制剂)的药时数值,以DAS1.0软件拟合其药动学参数,用方差分析和双侧t检验法检验其等效性。结果: 受试制剂与参比制剂的药动学参数分别为:t_1/2(5.24±1.58) h和(5.50±2.05) h,C_max(2.75±0.61) mg/L和(2.55±0.61) mg/L,T_max(0.99±0.56) h和(1.05±0.54) h,AUC_0-24(21.53±3.36) mg·L-1·h-1和(20.61±3.67) mg·L-1·h-1,AUC_0-∞(23.87±3.92) mg·L-1·h-1和AUC_0-∞(23.05±4.45) mg·L-1·h-1。受试制剂的相对生物利用度为(108.82±30.75)%。结论: 两种不同厂家的盐酸左氧氟沙星胶囊具有生物等效性。     

阿奇霉素片的人体相对生物利用度及药代动力学

目的研究阿奇霉素片受试制剂与参比制剂人体相对生物利用度及药代动力学。方法18名健康受试者自身交叉单剂量口服阿奇霉素受试制剂和参比制剂各500 mg,定时取血,用微生物法测定血药浓度。结果阿奇霉素片受试制剂与参比制剂的血药浓度时间曲线基本一致,符合一级吸收二房室模型。受试制剂与参比制剂的主要药动学参数分别为:消除半衰期t1/2β:(36.48±9.45)h,(38.10±9.39)h;Tmax:(2.39±0.61)h,(2.44±0.61)h;Cmax:(509.10±106.08)μg/L,(505.20±89.91)μg/L。药代动力学参数经配对t检验,差异均无显著性意义(P>0.05)。两种制剂的药时曲线下面积(AUC0-t)平均值分别为:受试制剂(9 080±1 339)(μg.h)/L,参比制剂:(9 308±1 390)(μg.h)/L;受试制剂的相对生物利用度为(98.0±10.1)%。结论受试制剂阿奇霉素与参比制剂生物等效。     

伊曲康唑分散片人体药动学及生物等效性研究

目的 研究伊曲康唑分散片受试制剂与参比制剂在健康志愿者体内的药代动力学和生物等效性. 方法 20名健康男性受试者随机双周期交叉单剂量口服伊曲康唑分散片受试制剂和参比制剂200mg,采用液相色谱-质谱-质谱联用测定不同时刻血浆中伊曲康唑的药物浓度,求出主要药物动力学参数.结果 伊曲康唑分散片受试制剂和参比制剂主要药代动力学参数TMAX 分别为(4.55±0.83)和(4.25±1.02)h,C MAX分别为(170.7±70.8)和(155.5± 73.3)ng/ml,tl/2分别为(19.3±4.6)和(20.4±11.4)h, AUCo-t分别为(2385±1281)和(2257±1168)ng h/mL,A 0-∞分别为(2496±1334)和(2371±1207) ng. h/mL.伊曲康唑分散片的相对生物利用度为(112.5±39.2) % .结论 伊曲康唑分散片和伊曲康唑胶囊为生物等效制剂.     

头孢拉定胶囊人体药代动力学和生物等效性

目的研究头孢拉定胶囊在健康人体内的相对生物利用度和生物等效性,为新药报批及其临床应用提供依据。方法20名健康受试者随机双交叉试验方法,单剂量口服受试及参比制剂500 mg,用HPLC法测定给药后不同时间的血药浓度,计算主要药代动力学参数。结果口服头孢拉定胶囊受试制剂和参比制剂后的主要药动学参数：T1/2分别为0.841±0.165和0.842±0.213 h;Cm ax分别为（15.922±2.584）和（15.922±2.584）mg/L;Tm ax分别为（1.225±0.197）和（1.225±0.242）h;AUC0-t分别为（25.399±5.806）和（26.159±5.989）mg/（L·h）。以AUC0-t计算,与参比制剂相比受试制剂中头孢拉定的平均相对生物利用度为（97.4±7.0）%。结论两制剂生物等效。     

头孢克洛胶囊健康人体药动学及生物等效性研究

目的:研究头孢克洛受试制剂和参比制剂的人体药动学和生物等效性.方法:20名健康受试者随机交叉口服受试制剂与参比制剂,剂量均为500 mg/人.采用HPLC法测定血中头孢克洛的浓度.结果:受试制剂与参比制剂的主要药动学参数Cmax分别为(13.31±3.57) mg/L、(12.81±3.02) mg/L; tmax 分别为(1.01±0.37) h、(0.96±0.31) h;t1/2分别为(0.47±0.25) h、(0.42±0.18) h;AUC0→tn分别为(19.63±3.21) mg·h/L-1、(20.06±2.89) mg·h/L-1.2种制剂的药动学参数相近,以AUC0→tn 计算的受试制剂的相对生物利用度为 (98.68±14.34)% .结论:受试制剂和参比制剂生物等效.     

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.