蜣螂急性毒性研究

目的 探讨蜣螂Catharsius molossus的毒性,明确蜣螂的毒性成分。方法 采用小鼠急性毒性实验,研究蜣螂乙醇提取物及其水提取部位的毒性;采用有机溶剂沉淀与凝胶色谱法分离蜣螂水提取部位的毒性成分。结果 小鼠ig给予剂量小于34.8 g/kg的蜣螂乙醇提取物,毒性很小,表明经口给药安全。蜣螂水提取部位有明显的急性毒性,主要症状为精神萎靡、呼吸异常、呆卧少动、对外界声刺激反应迟钝等,蜣螂水提取部位半数致死量（LD₅₀）为19.01 g/kg。蜣螂水提取部位中蛋白质质量分数约13%,相对分子质量在1.5×10³～3.0×10⁴,其中相对分子质量在3.0×10⁴左右的蛋白质可能是蜣螂水提取部位毒性成分之一。结论 蜣螂毒性与本草学描述相符。     

青蒿琥酯对口腔鳞癌Tca8113细胞及其移植瘤小鼠的抗肿瘤作用研究

目的 观察青蒿琥酯对口腔鳞癌Tca8113细胞增殖和凋亡的影响,以及对Tca8113细胞移植瘤小鼠肿瘤生长的影响。方法 用不同质量浓度的青蒿琥酯处理Tca8113细胞,HE染色观察细胞形态的改变;MTT法检测细胞增殖的情况;流式细胞仪检测细胞凋亡和细胞周期的变化。用口腔鳞癌Tca8113细胞建立口腔鳞癌淋巴道转移模型,ip给予移植瘤小鼠青蒿琥酯200 mg/(kg?d),连续给药10 d,观察青蒿琥酯对肿瘤生长抑制作用,以5-氟尿嘧啶（5-FU）作为阳性对照。结果 青蒿琥酯作用Tca8113细胞后,形态学观察可见细胞凋亡现象,部分细胞明显肿胀、变圆、变大,溶解成碎片,甚至死亡;细胞增殖受到抑制且呈时间、剂量相关性;青蒿琥酯能有效诱导Tca8113细胞凋亡并呈时间、剂量相关性,还能将Tca8113细胞阻滞在G₀/G₁期。体内实验显示,青蒿琥酯对Tca8113细胞移植瘤具有明显的抑制作用,抑瘤率为41.18%。结论 青蒿琥酯体内及体外对口腔鳞癌Tca8113细胞均有抑制作用,其机制可能与青蒿琥酯诱导细胞凋亡或改变细胞周期的分布有关。     

蟾酥抗肿瘤有效成分的活性追踪分离及急性毒性研究

目的 从传统中药蟾酥中寻找抗肿瘤活性强而毒性低的化合物。方法 采用追踪分离的方式,以体外肿瘤细胞生长抑制强度为活性指标,同时结合小鼠急性毒性实验,对蟾酥的主要化学成分进行初步研究。结果 采用活性追踪分离方式,从蟾酥中分离得到具有抑制肿瘤细胞生长活性同时对小鼠急性毒性较低的化合物蟾毒它灵,其对人非小细胞肺癌A549细胞具有较好的生长抑制作用,小鼠iv给药的LD₅₀约为蟾毒灵的4倍,而且稳定性较好。结论 综合化合物的活性、毒性及稳定性等因素,初步判断蟾毒它灵较其他同类化合物具有更好的抗肿瘤药物开发前景。     

双四氢呋喃型番荔枝内酯体内抗肿瘤作用

目的 研究双四氢呋喃型番荔枝内酯的体内抗肿瘤作用。方法 以紫杉醇为阳性对照,观察4个双四氢呋喃型番荔枝内酯单体番荔枝塔亭戊（squamostatin-E,1）、番荔枝塔亭甲（squamostatin-A,2）、去乙酰紫玉盘素（desacetyluvaricin,3）、泡番荔枝辛（bullatacin,4）对移植性肝癌Heps和肉瘤S₁₈₀荷瘤小鼠的抑瘤作用及对小鼠体质量与肝、胸腺和脾指数的影响。结果 与模型组比较,化合物1高剂量（60 μg/kg）、化合物3和4低剂量（15 μg/kg）对移植性肝癌Heps荷瘤小鼠肿瘤有极显著抑制作用（P＜0.01）,抑制率分别为51.6%、32.5%、63.4%;化合物2和3高剂量（60 μg/kg）对移植性肝癌Heps荷瘤小鼠肿瘤有显著抑制作用（P＜0.05）,抑制率分别为31.2%、70.9%;紫杉醇40 μg/kg的抑瘤率为62.2%。化合物3高剂量对移植性肉瘤S₁₈₀荷瘤小鼠肿瘤有极显著抑制作用（P＜0.01）,抑制率为63.9%;紫杉醇40 μg/kg的抑瘤率为48.9%。结论 化合物1～4对移植性肝癌Heps荷瘤小鼠、肉瘤S₁₈₀荷瘤小鼠均有明显抗肿瘤作用,部分化合物的抗肿瘤活性强于紫杉醇。     

黄芪桂枝五物汤对小鼠的急性毒性研究

目的 采用最大给药量的方法观察黄芪桂枝五物汤（浸膏）1日内ig给予受试动物后所产生的急性毒性反应,为多次重复给药毒性试验的剂量、可能作用的靶器官和毒性反应等指标的设计及临床剂量设计与观察提供参考依据。方法 以受试物最大允许质量浓度（0.6 g/mL）、小鼠最大给药容积（40 mL/kg）1日内ig给药2次,连续观察14 d内有无毒性反应及动物死亡。结果 测得黄芪桂枝五物汤（浸膏）最大给药量为48 g/kg（为临床用量的218倍）。在此剂量下未见明显毒性反应,14 d内动物无一死亡,大体解剖未见对脏器的毒性改变。结论 在本实验条件下,黄芪桂枝五物汤（浸膏）小鼠ig给药的最大剂量为48 g/kg,未见该剂量对小鼠产生明显的急性毒性。     

补骨脂素、异补骨脂素和补骨脂酚急性毒性的性别差异研究

[目的] 探究补骨脂素、异补骨脂素和补骨脂酚对小鼠急性毒性的性别差异。[方法] 补骨脂素给药剂量为雌性（1 125、843、633、475、356 mg/kg）、雄性（633、475、356、267、200 mg/kg）,异补骨脂素给药剂量为雌性（404、343、292、248、210 mg/kg）、雄性（317、292、269、248、229 mg/kg）,补骨脂酚雌、雄剂量均为2 000、1 765、1 500、1 200、1 020 mg/kg。一次性灌胃给予受试药,连续观察并记录14 d小鼠的毒性反应、体质量和死亡情况,应用SPSS统计学软件,采用Probit回归法计算半数致死量（LD₅₀）和95%可信区间。[结果] 给药后小鼠毒性反应主要表现为抽搐、四肢强直,部分动物口眼周围有分泌物,剂量越高反应越明显。与对照组比较,补骨脂素、异补骨脂素给药组随给药剂量增大,小鼠体质量呈现降低趋势。补骨脂素雌性小鼠的LD₅₀为514.35mg/kg,雄性小鼠LD₅₀为421.37 mg/kg,雌性小鼠LD₅₀值比雄性高出22%。异补骨脂素雌性小鼠LD₅₀为258.02 mg/kg,雄性小鼠LD₅₀为255.26 mg/kg。补骨脂酚雌性小鼠LD₅₀超出2 000 mg/kg,雄性小鼠LD₅₀为1 679.4 mg/kg。[结论] 补骨脂素和补骨脂酚对小鼠的急性毒性存在一定性别差异,但无统计学意义。     

白藜芦醇抑制A172脑胶质瘤细胞生长的研究

目的：研究白藜芦醇对A172脑胶质瘤细胞的生长抑制作用。方法：将A172细胞接种于96孔板上，每孔加入不同浓度的白藜芦醇，放入CO₂培养箱（37 ℃），培养24 h、48 h和72 h，用MTT（噻唑蓝）检测细胞的增殖活性。结果：白藜芦醇对A172脑胶质瘤细胞生长有抑制作用，且呈时间与剂量依赖性。结论：白藜芦醇对脑胶质瘤细胞的生长具有抑制作用，为临床进一步探讨脑胶质瘤的发病机制及应用中医药治疗脑胶质瘤提供了依据。     

甘草次酸及其衍生物TY501对小鼠巨噬细胞RAW264.7增殖的影响

目的 探究甘草次酸及其衍生物TY501对小鼠巨噬细胞RAW264.7增殖的影响。方法 以小鼠巨噬细胞RAW264.7为靶细胞,设置空白组,脂多糖（LPS）1 μg/mL处理组（模型组）,LPS 1 μg/mL加80、40、20、10 μg/mL药物处理组（受试药物TY501,对照药物泼尼松龙、甘草次酸、吡罗昔康）,每组设置4个复孔在给药刺激24 h后按照CCK-8试剂盒说明测定各药物对细胞增殖抑制率。结果 TY501半数抑制浓度（IC₅₀）为233 μg/mL,泼尼松龙IC₅₀为1 571 μg/mL,甘草次酸IC₅₀为31 μg/mL,吡罗昔康IC₅₀为14 187 μg/mL。结论 甘草次酸对RAW264.7巨噬细胞的增殖具有明显的抑制作用,甘草次酸衍生物TY501也可抑制小鼠巨噬细胞RAW264.7的增殖,在同等质量浓度条件下其对小鼠巨噬细胞增殖的抑制程度强于泼尼松龙,弱于甘草次酸,表明甘草次酸及其衍生物TY501对于小鼠巨噬细胞RAW264.7增殖的抑制作用可能是其发挥抗炎作用的机制之一。     

旻青蒿鳖甲方抗肿瘤炎症反应研究

目的 考察青蒿鳖甲方对肿瘤炎症反应的干预作用,分析其干预作用的量效关系以及君药青蒿及青蒿鳖甲组合在全方中的作用。方法 S₁₈₀荷瘤小鼠随机分为青蒿组（1.5 g/kg）,青蒿鳖甲组合组（1.5 g/kg）,青蒿鳖甲方低、中、高剂量（0.75、1.5、3.0 g/kg）组及模型组,每天ig给药1次,连续给药10 d。停药后称各组小鼠肿瘤质量,免疫组织化学法与Western blotting法检测肿瘤组织中环氧合酶-2（COX-2）、血管内皮生长因子（VEGF）蛋白表达,HE染色、光学显微镜计数白细胞,ELISA法测定荷瘤小鼠血清中肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、前列腺素E₂（PGE₂）水平。结果 青蒿鳖甲组合较单一青蒿有更强的抑瘤作用和较强的PGE₂抑制作用;青蒿鳖甲方明显升高细胞因子TNF-α、IL-1β水平,明显抑制COX-2、VEGF蛋白表达和肿瘤生长;青蒿鳖甲方低、中、高剂量抑制肿瘤生长的作用无明显量效关系。结论 青蒿鳖甲方通过对TNF-α和IL-1β的调控作用干预肿瘤炎症反应,进而产生抑制肿瘤生长作用。     

裂蹄木层孔菌抗肿瘤作用及其机制研究

目的 研究裂蹄木层孔菌的抗肿瘤作用及其机制。方法 制备S₁₈₀、H₂₂、MFC实体瘤小鼠模型和S₁₈₀腹水瘤小鼠模型。将3种实体瘤模型小鼠均分为模型组,裂蹄木层孔菌低、中、高剂量（0.5、1.0、2.0 g/kg）组和环磷酰胺（CTX）阳性对照组,S₁₈₀腹水瘤小鼠模型加设对照组。观察裂蹄木层孔菌对腹水瘤小鼠生存时间以及实体瘤小鼠瘤质量、胸腺和脾脏指数、血清中白细胞介素-2（IL-2）和肿瘤坏死因子-α（TNF-α）水平的影响。结果 与模型组比较,裂蹄木层孔菌低、中、高剂量均能延长S₁₈₀腹水瘤小鼠的生存时间（P＜0.05）,抑制肿瘤生长（P＜0.05）,提高胸腺和脾脏指数（P＜0.05）及血清IL-2（P＜0.05）和TNF-α水平（P＜0.01）。结论 裂蹄木层孔菌对小鼠肉瘤S₁₈₀、肝癌H₂₂细胞、前胃癌MFC肿瘤的生长有明显抑制作用,显示一定的抗肿瘤效应,其可能通过提高免疫器官指数及血清中IL-2、TNF-α的水平达到抗肿瘤目的。     

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.