替加氟磁性长循环热敏脂质体的制备及在大鼠体内的药代动力学研究

目的 研究替加氟磁性长循环热敏脂质体的制备、药动学规律和靶向性.方法 采用反相蒸发超声法制备替加氟磁性长循环热敏脂质体,采用高效液相色谱仪等检测替加氟在大鼠体内各组织中的药物浓度.结果 替加氟磁性长循环热敏脂质体平均粒径为126nm左右,具有强磁性和超顺磁性.磁控并加热的替加氟磁性长循环热敏脂质体组的肝内8 h药时曲线下面积是游离药物组的17.45倍,是替加氟长循环脂质体组的3.9倍;其肝外组织血浆、肾器官中比游离组低.其肝靶向效率达到73.9%.替加氟长循环脂质体组半衰期比替加氟游离药物组明显延长.结论 替加氟磁性长循环热敏脂质体显著增加药物在肝脏的分布,降低了药物的肾毒性.     

替加氟温度敏感性脂质体家兔体内动力学

目的:研究替加氟温度敏感性脂质体在家兔体内的动力学特点。方法:家兔静注替加氟温度敏感性脂质体,用微波电疗仪对肝脏局部加热至(42±0.1)℃,测定血中药物浓度变化,观察其体内动力学特点。结果:替加氟温度敏感性脂质体肝脏局部加热后,促进了药物在肝脏局部的释放,改变了其动力学特性,提高了替加氟温度敏感性脂质体的靶向性。结论:替加氟温度敏感性脂质体配合肝脏局部加热可提高其靶向性。     

丙酸氟替卡松鼻喷雾剂的研制及喷雾特性

采用高压均质工艺对丙酸氟替卡松原料进行微粒化,应用Box-Behnken效应面设计对微粒化工艺中均质压力、循环次数、混悬液药物浓度等3项参数进行了优化,得到的优化微粒化工艺为均质压力50 MPa、循环6次、混悬液药物浓度10%。在此基础上制备的丙酸氟替卡松鼻喷雾剂雾滴粒径分布及喷射模式均符合美国药典的要求,具有良好的喷雾特性。     

尼莫地平前体脂质体片剂的制备及释放度考察

目的制备尼莫地平前体脂质体片剂(Proliposome Tablet,PT),考察其体外的释放特性.方法以磷脂/β-环糊精为材料制备尼莫地平前体脂质体;采用湿法制粒将前体脂质体和其它辅料制备成为片剂;建立反透析法测定脂质体包封率;观察脂质体混悬液的粒径和形态;研究PT在不同溶出介质中的释放行为并考察压力、前体脂质体的粒子大小对药物释放的影响.结果尼莫地平前体脂质体片剂介质中释放符合Hixcon-Crowell方程,释放形成的脂质体溶液,平均粒径在212.7±12.98 nm,包封率达到71.8%.结论前体脂质体片剂制备方法可行,药物的体外释放符合Hixcon-Crowell方程.     

替加氟乳腺组织穿透及向氟尿嘧啶转化的药动学研究

目的 描述替加氟在血浆、乳腺肿瘤组织和正常组织中向氟尿嘧啶(5-FU)转化的药动学过程.方法 39名乳腺癌化疗病人po替加氟200 mg,同步采集血浆、肿瘤组织和相邻正常组织样品,并用HPLC测定替加氟和5-FU的浓度.使用自建的药动学模型拟合替加氟和5-FU的药-时曲线,并利用拟合参数计算血浆和乳腺组织中替加氟和5-FU的组织分布因子,以及替加氟向5-FU的转化率.结果 替加氟在肿瘤、邻近正常组织和血浆中的AUC分别为51.20,59.28 μg·h·g-1和156.44μg·h·g-1;半衰期分别为11.22,11.30和11.92 h.5-FU在肿瘤、邻近正常组织和血浆中的AUC分别为4.25,2.87 μg·h·g-1和1.68 mg·h·L-1.替加氟在正常组织中的组织分布因子(AUCTumor/AUCplasma)为0.33,肿瘤组织中的组织分布因子(AUCH-tissue/AUCplasma)为0.38;5-FU在乳腺肿瘤的组织分布因子AUCTumor/AUCplasma为2.53,正常组织的组织分布因子AUCH-tissue/AUCplasma为1.71.结论 血浆、乳腺肿瘤组织和相邻正常组织的药-时曲线拟合对替加氟转化为5-FU及5-FU消除过程进行了较好的描述.替加氟在乳腺肿瘤组织和相邻正常组织中的分布较为接近,其活性代谢产物5-FU在肿瘤组织中分布为血浆的2.53倍,为正常组织的1.71倍.替加氟在肿瘤组织中向5-FU的转化率较高.     

夏枯草有效部位结肠定位片大鼠体内评价

目的:考察夏枯草有效部位结肠靶向片剂与普通片剂体内药物组织分布的不同,评价该制剂的结肠定位性。方法:选择大鼠为实验对象,分别给予夏枯草有效部位结肠定位片剂及普通片剂,不同时间点分批处死大鼠,HPLC法测定大鼠胃、小肠上段、小肠中段、小肠下段、盲肠及结肠内容物中迷迭香酸的浓度,即采用测定药物组织分布浓度的方法比较结肠定位片剂与普通片剂在大鼠胃肠道各段分布。结果:夏枯草有效部位结肠定位片组大鼠口服给药后在大鼠胃和近端小肠不释放,进入小肠后,肠溶衣膜逐渐溶解,4 h左右于大鼠远端小肠开始释放药物,4~6 h在盲肠和结肠内大量释药,结肠组织中迷迭香酸的Cmax是普通组的3.6倍。结论:夏枯草有效部位结肠定位片组迷迭香酸在大鼠结肠组织中具有较高的分布量,具有结肠定位给药系统的释药特点。     

结肠菌群触发型5-氨基水杨酸壳聚糖胶囊大鼠体内的吸收与分布研究

目的 评价口服5-氨基水杨酸(5-ASA)壳聚糖胶囊后在大鼠体内的吸收与在结肠组织中的分布规律。方法 在轻度乙醚麻醉下通过聚乙烯管给大鼠口服5-ASA壳聚糖胶囊3粒(1．6mg／粒)，对照组口服5-ASA羧甲基纤维素混悬液1ml(4.8mg)。于给定的时间问隔从大鼠心脏取血，并取出结肠组织。用HPLC法测定大鼠血液及结肠中药物的浓度。结果 壳聚糖胶囊组血清中的时间-浓度曲线下面积(AUC0-12）是对照组AUC0-12的0．62倍；而结肠组织中壳聚糖胶囊组AUC0-12是对照组AUC0-12的3．62倍。结论 5-ASA壳聚糖胶囊具有较好的结肠定位靶向释药特性。     

16种具有P-gp抑制作用的上市药物对吉非替尼口服生物利用度和脑通透性的影响

采用LC-MS/MS法研究16种具有P-gp抑制作用的上市药物对吉非替尼口服生物利用度和脑通透性的影响。对照组ICR小鼠灌胃给予CMC-Na混悬液和吉非替尼混悬液，抑制剂组ICR小鼠分别灌胃给予16种上市药物混悬液和吉非替尼混悬液，血浆样品和脑匀浆样品经乙腈沉淀后，用LC-MS/MS法测定药物浓度。结果发现16种药物中利托那韦能够明显增加吉非替尼的口服生物利用度，吉非替尼血药浓度-时间曲线下面积(AUC)增加了2倍，同时增加了吉非替尼的脑暴露量，但是没有增加吉非替尼的脑通透性；部分其他药物也能增加吉非替尼的血浆AUC，不能增加吉非替尼的脑通透性；游离分数校正脑浓度发现对照组和给予利托那韦后，脑内游离药物浓度均不能达到体外抑制非小细胞肺癌(NSCLC)细胞生长的IC₅₀。本研究结果表明，临床剂量的16种具有P-gp抑制作用的上市药物虽然能够增加吉非替尼的口服生物利用度，但是不能特异性提高脑组织暴露量，需要研发特异性更强和更安全的P-gp抑制剂；用脑部药物游离分数校正脑浓度后，临床前研究发现脑暴露量不足可能是吉非替尼治疗脑转移疗效不理想的原因之一。     

盐酸伊立替康脂质体包封率的测定

目的：建立测定盐酸伊立替康脂质体包封率的方法。方法：通过微柱离心分离盐酸伊立替康脂质体和游离药物,以HPLC法测定药物含量,计算包封率。结果：Sephadex G-50微型柱可完全吸附盐酸伊立替康游离药物,空白脂质体回收率为98.2%～100.7%,脂质体和游离药物得到良好的分离;在选定色谱条件下,辅料不干扰测定,盐酸伊立替康质量浓度在1.1～10.6mg/L范围内线性关系良好（r=0.9997）,日内和日间精密度（RSD）均〈2%,加样回收率为97.6%～100.7%。结论：微柱离心-HPLC法可用于盐酸伊立替康脂质体包封率的测定。     

结肠菌群触发型5-氨基水杨酸壳聚糖胶囊大鼠体内的吸收与分布研究

目的评价口服5-氨基水杨酸(5-ASA)壳聚糖胶囊后在大鼠体内的吸收与在结肠组织中的分布规律。方法在轻度乙醚麻醉下通过聚乙烯管给大鼠口服5-ASA壳聚糖胶囊3粒(1.6mg/粒),对照组口服5-ASA羧甲基纤维素混悬液1ml(4.8mg)。于给定的时间间隔从大鼠心脏取血,并取出结肠组织。用HPLC法测定大鼠血液及结肠中药物的浓度。结果壳聚糖胶囊组血清中的时间-浓度曲线下面积(AUC0~12)是对照组AUC0~12的0.62倍;而结肠组织中壳聚糖胶囊组AUC0~12是对照组AUC0~12的3.62倍。结论5-ASA壳聚糖胶囊具有较好的结肠定位靶向释药特性。     

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.