完全弗氏佐剂雌性SD大鼠类风湿关节炎模型的建立及塞来昔布对其治疗效果

［］ 目的 寻找完全弗氏佐剂的最佳致炎剂量并考察不同给药方式对类风湿性关节炎的治疗效果,为患者提供更好的治疗方法。 方法 将18只雌性SD大鼠随机分成三组,用不同剂量的完全弗氏佐剂诱导SD大鼠构建关节炎佐剂模型,筛选出最佳剂量;然后另取18只大鼠随机分成3组：空白对照组、口服组、注射组,每组6只。口服组是用已上市的塞来昔布药物进行治疗,每天灌胃一次,每次20 mg。注射组是用自制的塞来昔布混悬液进行关节腔内局部注射治疗,每周给药一次,每次20 mg/kg。每3天为各组大鼠测量一次体重、足容积及足周长,随后再对其进行临床评分。最后,通过酶联免疫吸附实验(ELISA)检测各组大鼠的三种炎症因子：IL-1β、IL-6、TNF-α,并结合显微镜进一步观察组织病变情况。 结果 大鼠模型成功后第2天出现足爪红肿,全身及关节炎指数评分均有增加,炎症高峰期在免疫后19天。三种炎症因子的表达顺序为空白对照组>口服组＞注射组。治疗后的踝关节病理可见,空白对照组的滑膜组织增生,炎性细胞的浸润使血管翳出现,关节间隙狭窄甚至消失;而注射组正好相反。结论 10 mg/ml的卡介苗注射0.1 ml致炎构建成功,每周注射塞来昔布混悬液要比每天口服塞来昔布疗效好。     

塞来昔布治疗类风湿性关节炎疗效观察

目的探讨塞来昔布治疗类风湿性关节炎的疗效。方法将本院2009年12月～2010年6月收治的60例类风湿关节炎分为观察组和对照组。对照组采用常规治疗,观察组采用塞来昔布治疗。比较两组患者的临床疗效、关节疼痛指数、肿胀指数、握力、晨僵、血沉的变化及不良反应。结果观察组显效12例,有效9例,总有效率为70.0%显著高于对照组的50.0%,差异有统计学意义(P0.05)。且观察组的关节疼痛指数、肿胀指数、握力、晨僵和血沉的改善显著优于对照组,差异有统计学意义(P0.05)。观察组的不良反应显著少于对照组,差异有统计学意义(P0.05)。结论塞来昔布治疗类风湿性关节炎疗效较好,且不良反应较少,值得临床推广。     

依托芬那酯凝胶治疗双膝骨性关节炎疗效观察

目的：评价依托芬那酯凝胶治疗膝骨性关节炎患者的疗效和安全性。方法80例符合美国风湿病学院（ACR）膝骨性关节炎标准的患者纳入随机、塞来昔布对照组、双模拟研究,塞来昔布组200mg/d,局部依托芬那酯凝胶外用3次/d,治疗4周。结果经4周治疗后,治疗组的疗效指标[骨关节炎指数（62.4±13.9）、10米步行时间（9.1±0.9）、起立-行走计时测试（10.9±0.7）]均较治疗前明显改善（P<0.05）。结论应用依托芬那酯凝胶治疗膝骨性关节炎疗效与塞来昔布基本相当,而且依托芬那酯凝胶的作用更安全,无严重不良发生,安全性好。     

选择性COX-2抑制剂对大鼠胃溃疡微血管形成的影响及机制

[摘要] 目的：明确选择性COX-2抑制剂对实验性大鼠胃溃疡愈合和胃组织PGs代谢的影响,并从微血管形成的角度探讨其延缓胃溃疡愈合的机制。方法：以乙酸性大鼠胃溃疡模型为基础,观察选择性COX-2抑制剂塞来昔布对胃溃疡愈合的影响,以及对胃黏膜COX活性和PGE2含量、溃疡底部微血管数量、bFGF及其受体bFGFR mRNA表达的影响。结果：制模术后第9天,生理盐水组和塞来昔布组的溃疡面积分别为（11.9±3.1） mm2和（19.7±3.8）mm2（P<0.01）;制模术后第6天和第9天,塞来昔布组COX活性和PGE2含量均低于生理盐水组（P<0.01）;制模术后第9天,两组微血管数量分别为（42.9±6.8）个/视野和（30.6±6.2）个/视野（P<0.01）,塞来昔布组bFGF 和bFGFR mRNA水平均显著低于生理盐水组（P<0.01）。结论：选择性COX-2抑制剂对实验性大鼠胃溃疡愈合有显著延缓作用,其机理之一可能是通过影响胃溃疡大鼠胃组织PGs代谢,进而下调bFGF 和bFGFR mRNA表达以抑制胃溃疡底部的微血管的形成。     

塞来昔布联合莫西沙星对肺炎克雷伯杆菌肺炎大鼠肺部炎症标志物及组织病理学的影响

目的 研究特异性环氧化酶-2（COX-2）抑制剂塞来昔布联合莫西沙星对肺炎克雷伯杆菌肺炎大鼠肺部炎症标志物及肺组织病理学的影响。方法健康SPF级SD雄性大鼠60只,分2、4、6 d 3种给药疗程,各疗程20只大鼠随机分为5组：空白对照组（control组）、模型组（model组）、塞来昔布组（Cox组）、莫西沙星组（Mox组）、塞来昔布+莫西沙星组（Cox+Mox组）,每组4只。采用直视下气管插管接种肺炎克雷伯杆菌混悬液制作肺炎模型,control组予等量无菌生理盐水接种。药物治疗组在注射细菌混悬液后次日分别腹腔注射塞来昔布及莫西沙星,分别连续2、4、6 d。给药后第3、5、7天分批处死动物,使用ELISA法测定肺组织匀浆细胞因子、环氧化酶代谢产物及热休克蛋白90(HSP90)的水平;取肺组织进行病理学检查。结果2、4、6 d 3种给药疗程的各model组肺湿重/体重均较control组升高（P<0.05）,3种给药疗程的各Cox+Mox组与control组比较差异无统计学意义（P>0.05）,但均较model组降低（P<0.05）。给药4 d和6 d,model组的C反应蛋白(CRP)、肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6、IL-1β、转化生长因子（TGF）-β、HSP90、前列腺素I2（PGI2）、前列腺素E2(PGE2)、血栓素A2(TXA2)均较control组升高（P<0.05）,但IL-10较control组降低（P<0.05）;塞来昔布、莫西沙星及两药联合均可降低CRP、TNF-α、IL-6、IL-1β、PGI2、PGE2、TXA2（P<0.05）,塞来昔布联合莫西沙星未显示出优于单独使用塞来昔布或莫西沙星。但塞来昔布联合莫西沙星可提高IL-10（P<0.05）。肺组织病理学显示各model组的肺组织均出现明显炎症细胞浸润、肺泡间质出血、局部机化物形成等改变,塞来昔布、莫西沙星及两药联合的上述病理改变均较模型组减轻。结论塞来昔布、莫西沙星及两药联合可降低肺炎克雷伯杆菌肺炎大鼠肺部致炎细胞因子和前列腺素代谢产物水平,塞来昔布联合莫西沙星可提高抗炎因子IL-10水平。与单用塞来昔布或莫西沙星相比,两药联合在降低致炎细胞因子水平及改善肺组织病变作用方面并无显著优势。     

塞来昔布治疗骨性关节炎的临床观察

目的观察塞来昔布（西乐葆）对骨性关节炎的治疗效果并对其进行安全性评估。方法选择2006-2007年骨性关节炎病人60例分为2组，分别给予塞来昔布和双氯芬酸钠，给药后观察其治疗效果，并对塞来昔布和双氯芬酸钠的安全性进行评估。结果塞来昔布和双氯芬酸钠对骨性关节炎均有明显疗效，统计学上两者无明显差异；安全性方面塞来昔布优于双氯芬酸钠，统计学上差异有显著性。结论塞来昔布（西乐葆）抗炎镇痛疗效肯定，副作用较少，是一种安全性较佳的非甾体类抗炎药。     

颈腰痛丸治疗肝肾亏虚型腰椎骨关节炎的临床观察

目的观察颈腰痛丸治疗肝肾亏虚型腰椎骨关节炎的临床疗效和安全性。方法肝肾亏虚型腰椎骨关节炎80例患者，随机均分为A、B组，分别给予颈腰痛丸、塞来昔布治疗2周，SPSS 13.0分析治疗前后的疼痛视觉模拟评分（VAS）、汉化Oswestry功能障碍指数（ODI）、健康状况调查问卷SF-36（SF-36）、不良反应等差异。结果A组治疗前VAS、ODI、SF-36总分分别为7.26±2.34，24.80±6.63，597.82±130.28，治疗后为2.79±1.08，10.57±2.87， 634.38±147.86，治疗前后差异有显著性（t=3.07，4.27，6.33，P均<0.01），无明显不良反应。B组治疗前VAS、ODI、SF-36总分分别为7.68±3.07，23.97±6.87，602.28±140.17，治疗后为2.07±0.97，8.98±2.54，622.27±144.46，治疗前后差异有显著性（t=3.46，3.84，6.77，P均<0.01），2例不良反应。A、B组治疗后VAS、ODI差异无显著性（t=0.79，1.07，P=0.34，0.09），SF-36总分A组较B组高（t=1.70，P=0.04）。结论颈腰痛丸对肝肾亏虚型腰椎骨关节炎患者减轻疼痛和恢复腰椎功能方面具有塞来昔布近似的疗效，而不良反应更少且患者全身健康状况更佳。     

塞来昔布对大鼠蛛网膜下腔出恤后迟发性脑恤管痉挛的防治

目的探讨塞来昔布（Celecoxib）对迟发性脑血管痉挛的防治。方法36只SD大鼠随机分为对照组,蛛网膜下腔出血组,塞来昔布治疗组,每组12只。应用枕大池二次注血法建立大鼠SAH模型,治疗组第1次注血30rain后给予塞来昔布灌胃,利用HE染色和透射电镜分别观察各组处理后第7天基底动脉形态学和超微结构改变。结果（1）经塞来昔布治疗后,治疗组管径显著大于蛛网膜下腔出血组,管壁厚度显著小于蛛网膜下腔出血组（P〈0．05）,与对照组比较无显著性差异（P〉0．05）。（2）塞来昔布治疗后痉挛血管的形态学和超微结构得到改善。结论塞来昔布对蛛网膜下腔出血后迟发性脑血管痉挛有防治作用。     

塞来昔布联合盐酸氨基葡萄糖治疗膝骨性关节炎

目的探讨塞来昔布联合盐酸氨基葡萄糖治疗膝骨性关节炎的临床效果和安全性。方法选择我院2008～2011年收治的膝骨性关节炎患者64例,随机分为两组,每组各32例,观察组给予塞来昔布联合盐酸氨基葡萄糖治疗,对照组仅给予塞来昔布治疗,分别于治疗前、治疗后应用Lequesne评分标准指数评价关节功能改善情况,并对两组患者不良反应情况进行比较。结果两组患者经过治疗后Lequesne均显著下降,但观察组各项指标下降幅度显著好于对照组（P〈0.05）,且观察组在治疗6和12个月后关节软骨磨损阳性征象数目减少程度显著好于对照组（P〈0.05）。两组患者治疗期间均有不良反应情况发生,但发生率无显著性差别（P〉0.05）。结论塞来昔布联合盐酸氨基葡萄糖治疗膝骨性关节炎临床效果显著,可在控制症状、改善关节功能同时,长期维持疗效,并具有良好的胃肠道耐受性。     

探讨来氟米特、塞来昔布联合甲氨蝶呤片治疗类风湿性关节炎的临床效果

目的探讨分析来氟米特、塞来昔布联合甲氨蝶呤片治疗类风湿性关节炎的临床效果。方法分析2013年5月至2017年5月在我院进行治疗的类风湿性关节炎患者210例,通过不同的治疗方式进行分组,分为对照组105例与观察组105例,对照组患者采取来氟米特、塞来昔布治疗,观察组在此基础上联合甲氨蝶呤片治疗,比较患者治疗后的疗效与不良反应的发生情况。结果经过治疗后,观察组总有效率92.38%明显高于对照组的79.05%,差异具有统计学意义(P0.05);经过治疗后观察组患者不良反应出现9例,占8.57%,对照组患者不良反应出现10例,占9.52%,两组患者不良反应比较,差异无统计学意义(P0.05)。结论对类风湿性关节炎患者采取来氟米特、塞来昔布联合甲氨蝶呤片治疗,效果显著,降低不良反应发生率,安全性高,值得临床推广。     

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.