Exendin-4临床研究进展

Exendin-4是胰高血糖素样肽-1（GLP-1）受体激动剂,Exendin-4与GLP-1具有53%的同源性。GLP-1是主要的肠促胰素（进餐后肠道分泌的激素）,它通过葡萄糖依赖的方式促进胰岛素分泌、抑制胰高糖素分泌、延缓胃排空、增加饱腹感等作用维持血糖的稳定。在2型糖尿病（T2DM）患者中,它可以改善B细胞功能。天然的GLP-1半衰期很短,仅约2min,无法应用于临床;Exendin-4是从巨蜥唾液中分离得到的一种多肽,可与GLP-1受体结合,产生与GLP-1相似的生理效应,半衰期长达9.6h,用于治疗T2DM每天皮下注射两次可得到满意的疗效。临床研究显示Exendin-4可显著降低T2DM患者空腹及餐后血糖、HbA1c,显著降低体重和改善脂代谢。动物研究表明Exendin-4增加B细胞数量。由于Exendin-4的独特疗效,新近的糖尿病治疗指南已将其列入2型糖尿病的治疗药物。     

胰高糖素样肽1类似物治疗糖尿病的研究进展

胰高糖素样肽1(GLP-1)是一种肠肽类激素,GLP-1不仅可促进胰岛素合成和分泌、抑制B细胞凋亡、促进B细胞增殖、抑制胰高糖素分泌;还可降低食欲,延缓胃排空;GLP-1对心血管功能产生有益作用。人GLP-1类似物适用于二甲双胍、磺脲类和(或)胰岛素增敏剂控制血糖仍不满意的2型糖尿病患者。在1型糖尿病中,GLP-1对空腹血糖的作用,取决于患者血糖、胰升糖素水平及残存胰岛B细胞功能。GLP-1能改善餐后血糖的波动,根据患者残存B细胞功能的多少,其作用机制可能有差别。     

胰高血糖素样肽1受体激动剂对糖尿病以外疾病的临床应用

胰高血糖素样肽1(GLP-1)是由肠L细胞分泌的一种具有葡萄糖依赖性促胰岛素分泌功能的肠促胰素,近年来因其通过促进β细胞增殖与分化、抑制β细胞凋亡、抑制胰高血糖素分泌、抑制胃肠蠕动等方式实现血糖调节效应而成为2型糖尿病发病机制及药物治疗的研究热点。GLP-1受体不仅表达于胰腺,也广泛表达于胰腺外组织,包括胃肠道、心血管系统、中枢神经系统、肺、肾、骨骼、皮肤等,故GLP-1受体激动剂作为基于GLP-1的治疗方法对糖尿病以外疾病的治疗也有越来越多的研究。     

肠促胰岛素类似物和DPP-Ⅳ抑制剂在2型糖尿病治疗中的作用

肠促胰岛素类似物(incretin mimetics)是一类具有多种抗高血糖作用的新型降糖药物,它模拟胰升糖素样肽(GLP)-1的作用;二肽基肽酶(DPP-Ⅳ)抑制剂抑制GLP-1的降解。这两类药物的作用机制为:增加葡萄糖依赖的胰岛素分泌;抑制不适当的胰高血糖素分泌增多;增强胰岛素敏感性;减缓胃的排空;和抑制食欲。研究显示,肠促胰岛素类似物和DPP-Ⅳ抑制剂还具有促进胰岛β细胞新生的作用,可能会成为未来2型糖尿病(T2DM)治疗领域的新药。目前,几种肠促胰岛素类似物和DPP-Ⅳ抑制剂正在进行T2DM治疗的末期临床试验。     

肠促胰素效应与糖尿病

近年来,随着肠促胰素在糖尿病发病机制和药物治疗方面研究的不断深入,糖尿病的治疗有了新的思路.肠促胰素具有进食后刺激胰岛素分泌、抑制胰高血糖素分泌等多种生理功能,在维持血糖稳态上发挥了重要的作用.现将肠促胰素效应与糖尿病的关系进展综述如下.     

利拉鲁肽与阿卡波糖治疗新诊断2型糖尿病疗效比较

胰高血糖素样肽-1（GLP-1）作为重要的肠促胰素,近年来成为糖尿病研究领域的热点.利拉鲁肽是GLP-1类似物,具有降低血糖、保护胰岛β细胞功能、减轻体质量、调脂、心血管保护等作用,现在已经正式进入临床治疗.本研究对84例新诊断的T2DM患者分别进行利拉鲁肽、阿卡波糖为期12周的疗效观察,探讨其临床疗效.     

GLP-1类似物和DPP-4抑制剂在1型糖尿病治疗中的应用前景

1型糖尿病(T1DM)患者因自身免疫反应选择性破坏胰岛β细胞,呈现出胰岛素分泌绝对不足的临床特点,并同时伴有α细胞的胰高血糖素的不适当分泌.经典的T1DM治疗手段首选胰岛素的替代治疗.体外和体内试验均证实,激动胰高血糖素样肽(GLP)-1受体(GLP-1R)可致葡萄糖依赖的胰岛素分泌增加以及胰高血糖素分泌抑制,促进β细胞增殖分化及抑制β细胞凋亡,还可调节免疫反应减轻胰岛炎症,因而其相关药物对T1DM的治疗作用备受关注.本文回顾近期发表的通过GLP-1R激动效应治疗糖尿病的上市药物、包括GLP-1类似物和二肽基肽酶(DPP)-4抑制剂治疗T1DM患者的临床效果.     

胰高血糖素样肽-1的研究进展

胰高血糖素样肽-1（glucagon like peptide-1,GLP-1）是肠L细胞以营养依赖性方式分泌的一种具有葡萄糖依赖性促胰岛素分泌功能的肠促胰岛素,它还可通过促进β细胞增殖与分化、抑制β细胞凋亡、抑制胰高血糖素分泌、抑制胃肠蠕动等方式实现其血糖调节效应,因而已成为2型糖尿病发病机制及药物治疗中的研究热点。作者对近年GLP-1的生物学研究进展进行综述。     

胰高血糖素样肽-1类似物Exenatide的临床应用进展

胰高血糖素样肽-1（GLP-1）是由胰岛α细胞和肠黏膜L细胞分泌,具有促胰岛素分泌,抑制胰高血糖素分泌,延缓胃排空,降低体重等作用。而胰高血糖素样肽-1类似物（Exenatide,商品名Byetta）克服GLP-1T1/2短的缺点后,成功地在临床上应用了2年多,证明了作为磺脲类药物和二甲双胍等药物治疗不能达标的2型糖尿病患者的辅助用药,有助于改善患者长期空腹和餐后血糖及糖化血红蛋白的控制,还可减轻体重,给糖尿病治疗带来新契机。     

肠促胰素类药物对糖尿病患者动脉粥样硬化性心血管疾病作用的研究进展

作为动脉粥样硬化性心血管疾病（ASCVD）的高危人群,糖尿病患者对既能降低血糖水平又能减少或不增加ASCVD患病风险的药物的需求逐渐增加。鉴于心肌细胞上存在胰高血糖素样肽1受体（GLP-1R）,因此,肠促胰素类药物可能对糖尿病患者ASCVD产生作用。本文通过系统整理既往发表的国内外文献,对肠促胰素的结构与作用,肠促胰素对心肌细胞、心脏功能、血压、血脂水平等的影响进行综述,以期探讨肠促胰素类药物对糖尿病患者ASCVD的作用,为进一步研发既能降低血糖水平又起到保护心血管作用的药物提供依据,最终改善糖尿病患者尤其是合并ASCVD的患者的治疗效果和预后。     

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.