缺氧诱导因子-1α/Notch1通路在缺氧致病机制中的研究进展

缺氧普遍存在于多种疾病中。缺氧诱导因子-1α(HIF-1α)是细胞适应缺氧微环境的关键转录调节因子,Notch信号是传递缺氧反应的关键中间体,缺氧状态下Notch信号的激活独立于HIF-1α,HIF-1α与Notch1信号存在串扰,共同参与疾病的发生与发展。现就HIF-1α/Notch1通路在缺氧致病机制中的作用相关研究进展进行综述,为靶向缺氧途径提供新的策略。     

缺氧诱导因子1α与宫颈癌关系的研究进展

缺氧诱导因子1(HIF-1)是缺氧条件下广泛存在于哺乳动物和人体内的一种转录因子,是一种重要的缺氧应答调控因子,其生物学效应由HIF-1亚基实现的。HIF-1在维持氧稳定、细胞能量代谢、肿瘤血管形成、细胞增殖与凋亡等很多方面都起着重要作用。本文就HIF-1的生物学特性,HIF-1在宫颈癌发生中的作用和其对预后的影响等研究进展进行综述。     

缺氧诱导因子1与胃癌

缺氧诱导因子1(HIF-1)是一类介导缺氧适应性反应的转录因子,能调节许多缺氧反应基因的表达。HIF-1在维持氧稳定、细胞能量代谢、肿瘤血管形成、细胞增殖与凋亡等很多方面都起着重要作用。本文就HIF-1的生物学特性及其与胃癌的生长、浸润、转移、治疗、预后的关系予以综述。     

缺氧诱导因子1与肿瘤

缺氧诱导因子1(HIF-1)是一类介导缺氧适应性反应的转录因子,能调节许多缺氧反应基因的表达,是在缺氧条件下维持机体氧稳态的关键性物质。人类多数肿瘤内都有显著的缺氧区域,缺氧在肿瘤形成的病理过程中的重要作用与缺氧诱导因子及其调节的相关基因有关。因此,研究缺氧诱导因子与肿瘤的关系有重要的意义。本文就HIF-1的结构、功能及其与肿瘤的生长、浸润、转移、治疗的关系作一综述。     

缺氧诱导因子1与祛瘀生新

缺氧诱导因子1(hypoxia-inducible factor-1,HIF-1)是迄今为止发现的最重要的低氧转录调节因子之一。近年来,有关HIF-1在缺氧条件下对血管生成的作用引起了医学界的广泛关注。1992年,Semenza在缺氧诱导的细胞核提取物中发现了HIF-1,并于1995年成功克隆表达了HIF-1。HIF-1是一种基因转录的调节因子,在正常情况下不表达,缺氧条件下广泛存在于哺乳动物体内,具有多种生物活性。除了参与肿瘤的生长转移外,在缺血性心脏病、充血性心力衰竭、慢性肺病、脑梗塞、重度烫伤、闭塞性动脉硬化症及组织创伤等多种人类疾病和器官移植的病理生理过程…     

缺氧诱导因子-1调控卵泡发育的研究进展

缺氧诱导因子-1(hypoxia inducible factor-1,HIF-1)是一类介导缺氧适应性反应的转录因子,参与调节多种缺氧反应相关基因及其作用通路.卵泡发育的不同阶段及排卵过程通常处于缺氧的状态,HIF-1通过血管内皮细胞生长因子、促红细胞生成素、葡萄糖转运蛋白和糖酵解酶等靶基因,参与卵泡的发育调节.本文...     

缺氧诱导因子1与缺氧性肺动脉高压的研究进展

缺氧诱导因子1（HIF-1）是在缺氧条件下,广泛存在于哺乳动物和人体内的重要的转录调节因子.对低氧时组织细胞的信号转导起着重要的中介作用,通过对缺氧反应基因在转录水平的调节,从而使机体对缺氧刺激作出适应性的病理生理反应.HIF-1通过影响缺氧性肺血管收缩、肺血管重建、炎症发生及细胞凋亡等过程,参与缺氧性肺动脉高压（PHP）的形成.国内外学者通过对HIF-1与HPH相关性的探索和研究为临床HPH的治疗提供了一个新靶点.     

缺氧诱导因子-1与泌尿系肿瘤

1992年Semenza和Wang在低氧的肝癌细胞株Hep3B细胞的核提取物中发现一种蛋白特异性地结合于红细胞生成紊(EPO)基因增强子的寡核苷酸序列．命名为缺氧诱导因子-1(HIF-1)。缺氧诱导因子-1(hypoxia—inducible factor L HIF-1)是缺氧条件下广泛存在于哺乳动物和人体内的一种转录因子。作为细胞氧平衡和缺氧诱导基因表达的中心调节子。HIF-1在缺氧条件下。其α蛋白水平和与DNA结合活性增加。缺氧的微环境存在于多数肿瘤组织中．近年研究表明HIF-1与肿瘤发生、发展密切相关。它不仅在肿瘤细胞及其转移灶细胞中过度表达；而且能诱导肿瘤组织中异常基因的表达；同时对肿瘤细胞生长与凋亡均有重要影响。     

缺氧诱导因子-1与肾脏疾病

缺氧诱导因子-1（hypoxia-inducible factor-1，HIF-1）是哺乳动物和人体细胞内存在着的一类介导缺氧适应性反应的转录因子，能激活许多缺氧反应性基因的表达。HIF-1在以下几方面与肾脏关系特别密切：首先，HIF-1是促红细胞生成素（EPO）的主要调控者，而肾脏又是EPO的主要产生场所，且许多肾脏疾病可显著影响EPO的生成；其次，在正常情况下部分肾脏也处于低氧张力状态，肾脏易受低氧和低灌注的影响；再次，绝大多数肾透明细胞癌都有HIF-1的组成性表达，这是由于VHL（von Hippel-lindau）肿瘤抑制基因对调控HIF-1起关键作用，而VHL基因遗传缺陷是患肾透明细胞癌的高危因素，表明HIF-1在调控肾上皮细胞行为中具有特别作用。     

金雀异黄素抑制缺氧人视网膜色素上皮细胞VEGF表达机制的初步研究

目的:进一步明确金雀异黄素(Gen)抑制缺氧人视网膜色素上皮细胞(RPE)血管内皮生长因子(VEGF)表达的机制。方法:以体外正常情况为对照,建立人RPE缺氧模型并经不同浓度Gen干预后,通过RT-PCR检测VEGF及其转录调节因子c-fos、c-jun、缺氧诱导因子(HIF)-1α、HIF-2α、HIF-3αmRNA的表达水平,了解Gen是否通过对VEGF的转录因子活性调节而影响VEGF的表达。结果:缺氧能使人RPE细胞的VEGF、c-fos、c-jun及HIF-2α、HIF-3αmRNA水平增高,对HIF-1α无影响;Gen能抑制缺氧诱导的VEGF表达;在所检测的VEGF转录因子中,Gen只对HIF-2α的转录有抑制作用。结论:Gen抑制VEGF表达的作用部分是通过抑制其转录调节因子HIF-2α转录实现的。     

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.