大黄酚脂质体的制备及其质量评价

目的 研究大黄酚脂质体的最佳制备工艺和处方,并对其进行质量考察。方法 采用薄膜-超声分散法制备大黄酚脂质体,以包封率为评价指标,采用单因素和正交试验法优化大黄酚脂质体的制备处方和工艺条件,并观察其粒径、形态及稳定性。结果 大黄酚脂质体优化后的制备处方和工艺条件为：胆固醇与大豆卵磷脂质量比为1∶3,药脂比为1∶10,pH值为8.2,成膜温度为45 ℃。按该处方工艺制备的大黄酚脂质体包封率在87%以上。结论 优选处方和制备工艺稳定可行,制备的大黄酚脂质体包封率和稳定性高,粒径均匀。     

盐酸青藤碱脂质体的制备工艺研究

目的 提高盐酸青藤碱（sinomenine hydrochloride,SIN-HCl）脂质体的药物包封率,并阐明处方药量与脂质体粒径等因素对包封率的影响规律。方法 以离心沉淀-离心超滤法测定SIN-HCl脂质体的包封率;以包封率与成型性为主要指标筛选薄膜分散法（TFH）、逆相蒸发法（REV）与乙醚注入法（EI）3种制备方法;考察水化液的种类、pH值、离子浓度以及pH梯度载药、磷脂-胆固醇比例、药脂比对包封率的影响;以全面设计试验考察处方药量与粒径两因素对包封率的影响规律;考察代表性脂质体样品在4 ℃下的稳定性。结果 最适的制备工艺为薄膜分散法;最佳水化液为柠檬酸缓冲液（CBS）;随着水化液pH值的升高,包封率增加;当水化液的pH值相同时,脂质体包封率随着水化液离子浓度的降低而增加;pH梯度载药可提高脂质体的包封率,pH梯度载药脂质体的最适水化液为pH值2.5的CBS,最适大豆磷脂-胆固醇比例为6∶1,SIN-HCl与大豆磷脂的比例由1∶6增至6∶6,未经探针式超声处理的脂质体包封率略有下降;建立了药物包封率与处方药量和粒径之间的定量关系,一定粒径与处方药量的脂质体包封率大于80%;成品脂质体的稳定性良好。结论 pH梯度主动载药技术可以制备高包封率的SIN-HCl脂质体。     

硫酸铵梯度法制备槐定碱脂质体的研究

目的 对槐定碱脂质体的处方进行考察并优化。方法 硫酸铵梯度法制备槐定碱脂质体,采用单因素对影响包封率的处方因素进行初步筛选,以包封率、载药量及综合评价为指标,采用星点设计考察药物及硫酸铵浓度对制备工艺的影响,对结果进行多元线性和二项式拟合,效应面法选取最佳工艺条件进行预测分析。结果 从复相关系数上看,各指标二项式拟合方程均优于多元线性回归方程,根据优化工艺制得的槐定碱脂质体包封率为51.81%、载药量为5.39%。结论 优选的槐定碱脂质体制备工艺稳定可行。     

重组水蛭素-2鼻腔给药纳米粒制备工艺研究

目的 优选重组水蛭素-2（rHV2）鼻腔给药纳米粒最佳制备工艺。方法 采用壳聚糖与三聚磷酸钠复凝聚法,以包封率、载药量等为评价指标,以单因素考察和正交试验设计,对壳聚糖黏附纳米粒制备过程中有关影响因素及工艺参数进行优化。结果 壳聚糖的类型、壳聚糖溶液的pH值、壳聚糖与多聚磷酸钠的最终质量比以及搅拌速率对rHV2纳米粒的包封率和载药量均有较显著影响;优选工艺的包封率可达到70%以上,载药量＞8%。结论 经优选的工艺稳定可靠,可用于rHV2鼻腔给药纳米粒的制备。     

白黎芦醇脂质体的制备工艺改进

目的: 制备白黎芦醇脂质体,优选最佳处方及最佳制备工艺. 方法: 以大豆磷脂、胆固醇为载体,采用薄膜超声分散法制备白黎芦醇脂质体,设计正交实验,以包封率、形态为考察指标选择最优处方. 结果: 按最优处方制得的白黎芦醇脂质体均匀圆整,平均粒径范围80～100 nm,包封率为96.52%,载药量为19.81%. 结论: 选择薄膜超声分散法优化工艺制备白黎芦醇脂质体处方合理,工艺可行,包封率及载药量高.     

β-榄香烯脂质体的制备工艺研究

目的确定β-榄香烯脂质体较佳的配方组成和制备方法。方法比较薄膜水化(TFH)、逆相蒸发(REV)和REV结合高压挤压法制备β-榄香烯脂质体方法,优选出较优的制备方法;光子相关衍射法测量β-榄香烯脂质体的粒径;气相色谱法测定包封率。结果薄膜水化法制备的β-榄香烯脂质体的包封率大于逆相蒸发法脂质体的包封率,但该法不易于批量生产。逆相蒸发法脂质体经高压挤压后在一定挤压程度内,粒径减小、包封率和载药量增加,所制得的β-榄香烯脂质体稳定性良好,6个月未发现凝絮分层现象。结论逆相蒸发结合高压挤压方法制备的β-榄香烯脂质体粒径小而分布较均匀,且有较高的载药量和包封率。     

正交试验优选石杉碱甲脂质体的制备研究

目的 优化石杉碱甲脂质体的制备工艺和处方。方法 采用薄膜分散结合硫酸铵梯度法制备石杉碱甲脂质体,以包封率为评价指标采用正交试验优化石杉碱甲脂质体的最优处方和工艺条件。结果 石杉碱甲脂质体的最优处方工艺条件为：孵化温度为60 ℃,药脂比为1∶40,孵化时间为30 min。所得脂质体的包封率为87.02%以上。结论 由最佳处方工艺条件制备的石杉碱甲脂质体包封率较高,包封率和体外释放稳定,重现性好。     

复乳法制备龙胆苦苷脂质体

目的 以大豆卵磷脂和胆固醇等为载体制备龙胆苦苷脂质体。方法 采用复乳法考察乳化剂的用量、药脂比、磷脂与胆固醇质量比等因素对脂质体制备过程的影响;以外观形态和包封率为考察指标,优化龙胆苦苷脂质体的最佳制备工艺。结果 复乳法制备的龙胆苦苷脂质体最佳工艺为：大豆卵磷脂与胆固醇质量比为6∶1,药脂比为1∶8,助乳剂量为30∶1,包封率可达82%。结论 复乳法制备龙胆苦苷多囊脂质体均匀、稳定,粒径分布（414.8±50.0）nm,Zeta电位为（?29.2±5.0）mV。     

甘草次酸-丹参酮IIA复方脂质体处方优化及制备工艺研究

目的 研究甘草次酸（GA）-丹参酮II_A（Tan II_A）复方脂质体（GT-Lip）的制备工艺。方法 以大豆卵磷脂（SPC）和胆固醇（Ch）为膜材,薄膜分散探头超声法制备GT-Lip。通过单因素考察确定水合温度和探头超声功率,正交设计法优化处方工艺;低速离心法测定脂质体中GA与Tan II_A包封率,动态光散射粒径仪测定脂质体粒径与Zeta电位,透射电镜测定脂质体形态。结果 优化处方工艺为SPC-Ch质量比6∶1,SPC-Tan II_A物质的量之比30∶1,SPC-GA物质的量之比24∶1,水合温度为30 ℃,探头超声条件为380 W超声5 min;制备得到的GT-Lip中Tan II_A、GA的包封率分别为（81.50±0.76）%、（98.63±0.90）%（n＝3）,平均Zeta电位为（?19.00±0.98）mV（n＝3）,平均粒径为（120.5±1.62）nm（n＝3）。结论 优化的GT-Lip制备工艺稳定可行。     

Box-Behnken效应面法优化多西他赛长循环脂质体处方

目的 优化多西他赛长循环脂质体（DLCL）处方。方法 采用薄膜蒸发法制备DLCL,分别以卵磷脂（PC）与多西他赛（DOC）质量比（X₁）、PC与胆固醇（Chol）质量比（X₂）、DSPE-PEG 2000与PC物质的量之比（X₃）为考察对象,包封率（Y₁）、载药量（Y₂）、综合指标OD值为评价指标,采用Box-Behnken效应面法筛选DLCL的最佳处方。结果 最优处方为X₁＝0.616 2,X₂＝1.0,X₃＝?1.0;DLCL的包封率为（94.71±1.75）%,载药量为（5.37±0.43）%,标准偏差均小于10%;平均粒径139.6 nm,分布均匀,体外释放试验结果表明其具有明显的缓释效果。结论 采用Box-Behnken效应面法优化DLCL处方是有效、可行的。     

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.