一种高稳定性钆类核磁共振成像造影剂的合成

合成了一种基于氮氧化二乙烯三胺五乙酸（DTPA）二异丙胺双酰胺的钆配合物,兼具高弛豫率和高稳定性。通过高分辨质谱、核磁谱图确认了氮氧化配体及对应的钆配合物的结构,并通过电位滴定法测得其配位稳定性常数。实验结果表明此配合物的水合常数为3,弛豫率（16.39 mM^-1·s^-1）达到商用造影剂的3倍,稳定性优于商用造影剂Gd-DTPA-BMA（Omniscan^®）且表现出良好的成像效果以及优异的生物相容性,具有投入临床应用的巨大潜力。     

基于三(2-氨基乙基)胺和6-羧基荧光素的双模式核磁共振成像造影剂

通过将三（2-氨基乙基）胺（TREN）、6-羧基荧光素与溴乙酸苄酯结合而合成出多胺多羧型配体,并赋予化合物荧光成像的功能。进一步与顺磁性的六水合氯化钆（Ⅲ）反应获得兼具核磁共振成像（Magnetic Resonance Imaging,MRI）和光学成像功能的双模式核磁共振成像造影剂。通过核磁氢谱、碳谱、高分辨质谱和ICP-AES表征了配体和金属配合物的结构。研究结果表明,该配合物的纵向弛豫率（r₁）为3.46 mM^-1·s^-1,与小分子型商用造影剂如马根维显^®（Gd-DTPA）接近。该配合物同时拥有66%的荧光量子产率,在紫外光照射下显示明亮的绿色荧光,为以后进行生物体内研究打下坚实基础。     

双吗啉类PI3Kα抑制剂的自组织分子场分析

采用自组织分子场分析(SOMFA)构建了39个双吗啉类磷脂酰肌醇-3激酶α(PI3Kα)抑制剂的三维定量构效关系模型。交叉验证相关系数(q²)、非交叉验证相关系数(r²)、标准偏差(SEE)分别为0.636、0.702和0.581,立体场和静电场的贡献分别为0.7和0.3,并用测试集进行了验证。测试集非交叉验证相关系数(r²_pred)为0.808。该模型具有显著的统计学意义,为进一步开发新的双吗啉类PI3Kα抑制剂奠定了基础。     

水杨醛亚胺类镍系配合物的合成及其催化乙烯聚合

合成了一系列含不同取代基水杨醛亚胺配体L₁~L₅,及相应镍配合物C₁~C₅,并用核磁共振(¹H-NMR)、红外光谱(IR)、质谱(Mass)和元素分析(EA)等手段对配体及配合物进行了表征。以C₃为单组分催化剂,研究了在不同聚合条件下单组分催化剂对乙烯聚合的影响,结果表明在极性溶剂二氯甲烷中单组分催化剂显示出高的催化活性,甚至在二氯甲烷与水的混合溶剂中也具有一定的聚合活性。以     

二氢嘧啶酮类α1A-肾上腺素受体拮抗剂的比较分子力场分析

采用比较分子力场分析(CoMFA)构建了二氢嘧啶酮类α_1A-肾上腺素受体拮抗剂的三维定量构效关系模型。交叉验证相关系数（q²）、非交叉验证相关系数（r²）和标准偏差（SEE）分别为0.604、0.987和0.105,研究结果显示静电场对活性的影响大于立体场。所构建的模型具有一定的预测能力,可用于指导设计新的二氢嘧啶酮类α_1A-肾上腺素受体拮抗剂,为该类化合物的结构优化提供理论依据。     

硫化氢供体型美金刚衍生物的合成及其活性

H₂S具有保护缺血再灌注损伤的神经元、显著降低脑梗死面积的作用,但高浓度H₂S产生神经毒性。N-甲基-D-天冬氨酸(NMDA)受体拮抗剂美金刚可以降低高浓度H₂S引起的神经毒性。将硫化氢缓释供体5-对羟基苯基-1,2-二硫杂环戊烯-3-硫酮(ADT-OH)与美金刚通过烷烃连接臂拼合,设计了9个结构全新的化合物I₁~I₉,以ADT-OH为原料,经过4步反应得到目标化合物,其化学结构经¹H NMR、¹³C NMR和HRMS确证。利用MTT法评价不同浓度目标化合物对谷氨酸损伤的HT-22细胞的影响,结果发现,该类化合物在1 μmol/L时能明显提高受损HT-22细胞的生存率(P<0.01),对于谷氨酸诱导损伤的神经元细胞具有较好的保护作用。     

(E)-1,2-二芳基取代乙烯类化合物的合成及抗血小板聚集活性

在2-溴苄基膦酸二乙酯结构基础上,合成两个系列(E)-1,2-二芳基取代乙烯类化合物Ⅴ₁～Ⅴ₉ ,Ⅵ₁～Ⅵ₄),并对所合成的化合物进行抗血小板聚集活性实验。合成了13个未见文献报道的目标化合物,结构经元素分析、红外光谱、核磁共振氢谱、质谱确证。初步生物活性测试表明,多数化合物具有不同程度的抗血小板聚集活性,其中化合物Ⅴ₄、Ⅴ₉的活性较好。结果表明,(E)-1,2-二芳基取代乙烯类化合物是一类新型的具有潜在价值的抗血小板聚集活性的化合物。     

硫化氢供体型ADT-OH衍生物的合成及其活性

二硫杂环化合物5-对羟基苯基-3H-1,2-二硫杂环戊烯-3-硫酮(ADT-OH)是一种缓释硫化氢供体,并具有一定的神经保护作用。为了研究其构效关系,对其芳环进行改造,合成了17个Y类化合物(Y₁~Y₁₇),其结构均经 ¹H NMR、¹³C NMR 和HR-MS确证,其中6个化合物(Y₄,Y₁₃~Y₁₇)结构是全新的。采用MTT法评价了该类化合物对谷氨酸诱导损伤的HT-22海马神经元细胞生存率的影响,结果发现,这些化合物在1~100 μmol/L浓度范围内具有很强的神经保护作用,其中化合物Y₁~Y₉,Y₁₁在全部测试浓度内均能非常显著地提高受损神经元的生存率(P<0.01),特别是化合物Y₁,Y₄,Y₆~Y₉,Y₁₁在1~10 μmol/L浓度范围内活性比ADT-OH强,值得进一步研究。     

水杨醛亚胺锆络合物的合成及其催化乙烯聚合

以3-叔丁基-5-甲氧基水杨醛和邻取代苯胺为原料,合成了两个水杨醛亚胺配体（1,2）及相应的锆络合物（3,4）。用质谱（MS）、核磁共振氢谱（¹H-NMR）和核磁共振碳谱（¹³C-NMR）等方法表征了配体及络合物的结构,采用流变仪、差示扫描量热仪（DSC）对聚合物进行了分析。研究了乙烯压力、聚合温度、时间、溶剂、铝锆物质的量之比（n_Al：n_Zr）等对络合物催化性能和聚乙烯分子量的影响。结果表明,在甲基铝氧烷（MAO）的助催化下,锆络合物在甲苯中对乙烯聚合具有较好的催化活性,所得聚合物为超高分子量聚乙烯。在30℃、0.9 MPa下,络合物4在正己烷中的催化活性达到60.2 kg/（mmol·h）,聚乙烯的黏均分子量最高可达6.6×10⁶,分子量分布为2.4,聚合过程具有良好的可控性。     

4-(N-芳基)胺基-6-长链烷氧基取代蝶啶类化合物的合成及其抗肿瘤活性

采用具有喹唑啉为母核的抗肿瘤药物作为先导化合物,利用生物电子等排原理,设计并合成一系列4-(N-芳基)胺基-6-长链烷氧基取代蝶啶类化合物7a~7l,并利用MTT法测试其对A549、KG1a和HGC-27肿瘤细胞的增殖抑制作用。以3-氨基吡嗪-2-羧酸甲酯为起始底物,通过6步反应合成12种目标化合物(7a~7l)并确证其结构(¹H NMR、¹³C NMR、MS)。生物活性试验表明,蝶啶4位为2-氯-5-硝基苯胺基取代时,其活性均高于其他苯胺基取代的产物。化合物7b对A549的活性(IC₅₀=11.55 μmol/L)与阳性对照物吉非替尼(IC₅₀=5.95 μmol/L)十分接近;化合物7k对3组细胞的IC₅₀均十分接近对照物吉非替尼。由于筛选出的化合物均有2-氯-5-硝基苯胺基片段,可以此结构为基础进行深入研究。     

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.