补骨脂酚启动自噬减轻β-GP诱导的小鼠主动脉中膜钙化

目的：在选定的36种中药单体中筛选能够启动细胞自噬的药物;探究补骨脂酚对小鼠血管平滑肌细胞自噬的影响以及对血管平滑肌细胞钙化的影响。方法：从中草药中提取的黄酮类化合物以不同浓度处理人脑胶质瘤细胞(human glioma cells,U87)72 h,用MTT法得到药物对U87细胞的半抑制浓度(half maximal inhibitory concentration,IC₅₀),并以小于IC₅₀浓度的条件下以不同浓度梯度处理U87细胞,观察U87细胞GFP-LC3(微管相关蛋白1轻链3(Microtubule-associated protein light chain 3,LC3)的荧光信号和Western blot检测自噬指标LC3从而观察细胞自噬活动激活情况,以筛选出能够启动自噬的药物。后续选取补骨脂酚进行进一步实验,探究药物启动自噬后对血管平滑肌细胞钙化的影响。使用β-GP构建小鼠血管平滑肌细胞(vascular smooth muscle cells,VSMCs)钙化模型,分为对照组(C-CTR组)和钙化组(C-CAL组),并通过...     

HIF-1介导的自噬在慢性肾脏病血管钙化中的研究进展

血管钙化是慢性肾脏病患者的主要心血管风险因素,会增加慢性肾脏病患者的全因致死率。对于慢性肾脏病患者,长期的矿物质代谢紊乱、信号通路异常激活、激素水平改变及表观调控遗传异常基因表达等因素均会加速血管钙化。而血管平滑肌细胞的表型转换在血管钙化过程中发挥关键作用。自噬作为一种普遍存在的细胞内分解代谢过程,已被证实与血管平滑肌细胞的表型转换、凋亡有密切联系。低氧诱导因子-1(HIF-1)作为机体重要的转录因子,在低氧状态下可被上调并诱导下游靶基因BNIP3蛋白增加,促进自噬小体形成,从而改善心肌缺血的损伤程度,增强心肌保护。HIF-1介导的自噬可能是慢性肾脏病血管钙化的药物干预和治疗的新型靶点。     

m6A与糖尿病创面关系的相关研究进展

N6-甲基腺苷(N6-methyladenosine,m6A)是真核细胞中最普遍、最丰富的转录后RNA修饰类型.近年来有研究表明m6A在细胞分化及免疫/炎症反应等过程中有重要的调控作用.糖尿病创面愈合受炎症细胞因子、巨噬细胞、自噬、血管生成等多种因素的影响.越来越多的研究证明,炎症细胞因子、巨噬细胞、自噬、血管生成、骨...     

平滑肌细胞自噬在血管疾病中作用的研究进展

自噬在体内对于维持血管正常功能和结构发挥至关重要的作用。当受到应激刺激时,自噬水平增加,进 一步促进细胞存活、表型转化及减轻钙化,从而避免增殖性血管疾病的发生,对血管平滑肌细胞起保护作用。相 反,平滑肌自噬水平降低可促使细胞衰老,导致血管舒缩功能异常和结构改变,参与血管老化的进展。然而,自噬 过度激活会损伤平滑肌细胞内正常的蛋白质和重要细胞器,甚至引发自噬性细胞死亡,加速血管疾病的进程。因 此,充分利用自噬有利的一面,精确调控自噬或将成为治疗血管疾病的一种崭新方式。     

自噬参与氧化性低密度脂蛋白诱导的血管平滑肌细胞钙化

【目的】 观察细胞自噬是否参与了氧化型低密度脂蛋白(Ox-LDL)诱导的血管平滑肌细胞钙化｡【方法】 采用体外血管平滑肌细胞钙化模型,实验分为3组:control组:用native LDL处理细胞;Ox-LDL组:用Ox-LDL处理细胞;3MA组:用Ox-LDL和3MA处理细胞;细胞培养液为DMEM+10mM BGP｡分别以茜素红检测血管钙化,Q-PCR 和Western blotting 测定cbfa1和Beclin1的mRNA 和蛋白表达｡【结果】 Ox-LDL加速血管平滑肌细胞钙化,上调cbfa1 和Beclin1的表达;细胞自噬特异性抑制剂3MA减弱细胞钙化,下调cbfa1 和Beclin1的表达｡【结论】 Ox-LDL诱导的血管平滑肌细胞钙化与细胞自噬有关｡     

sirt1调控自噬在心肌缺血/再灌注损伤中的研究进展

心肌再灌注治疗是急性心肌梗死(AMI)的治疗方法之一,能够显著改善预后,降低死亡率,但早期往往会增加心肌细胞损害,引起心肌缺血/再灌注(ischemia/reperfusion,I/R)损伤。自噬在真核细胞中广泛存在,适度的自噬对机体的生长发育起到保护作用,自噬不足或者过度自噬对机体有损害作用。然而,在心肌I/R中,缺血阶段的自噬起到保护作用,在再灌注阶段起到损害作用。沉默信息调节因子1(sirt1)作为一种去乙酰化酶,可通过调控相关蛋白的去乙酰化而在氧化应激、细胞代谢、炎症反应、细胞凋亡等多种过程中发挥重要作用。近年来,sirt1参与自噬的发生机制逐渐受到关注,探索sirt1调控自噬在心肌I/R损伤中的作用,有助于对心肌I/R损伤的发病机制展开研究。     

细胞自噬在肿瘤发生、转移与治疗中的作用

自噬与肿瘤的关系是近年来的研究热点。既往研究表明,自噬是肿瘤发生和转移过程中的双刃剑;自噬调节剂与细胞毒性药物联用在临床应用上具有很大潜力。本文对自噬在肿瘤发生、转移与治疗中的作用进行综述。     

严重烧伤早期血管内皮细胞自噬的研究进展

严重烧伤早期血管通透性增加,可继发休克,其主要原因在于血管内皮细胞受损;损伤的血管内皮细胞可成为早期损害的“激发器”,导致多脏器损害。自噬是细胞维持自身结构和功能稳态的重要机制,也是哺乳动物细胞降解及回收利用大分子和细胞器的主要代谢通路,在清除蛋白聚集或损伤的细胞器、维持细胞内稳态、保持细胞健康过程中发挥着重要作用,近年来已成为关注的热点之一。应激、缺氧和炎症因子等均可刺激血管内皮细胞发生自噬,而自噬可影响细胞的结构和功能,调节凋亡过程。该文就严重烧伤血管内皮细胞自噬的研究进展进行了综述。     

PTEN与糖尿病患者血管钙化关系的研究进展

血管钙化是糖尿病患者普遍存在的病理表现,研究表明血管钙化是一个类似于骨发育和软骨形成的主动的、可调节的、可治疗和预防的过程。血管钙化过程中必然伴随血管平滑肌细胞的死亡,已有研究表明血管平滑肌细胞的凋亡参与了血管钙化的发生。PTEN是发现最早的具有磷酸酶活性的抑癌基因,对细胞的增殖、凋亡、迁移和血管生长等多种生物学活动中有重要调节作用,已有研究表面PTEN可促进血管平滑肌细胞的凋亡。过往,人们对PTEN的研究主要为其在肿瘤领域的作用,近年来,随着研究的深入,人们发现其在血管钙化中也发挥重要的作用。本文就PTEN与糖尿病患者血管钙化关系的研究进展作一综述。     

宫颈癌、miRNA、自噬相互间关系研究进展

宫颈癌是常见的女性生殖道恶性肿瘤,严重威胁女性的健康。对其具体发病机制至今尚未阐明,但目前已有研究表明mi RNA、细胞自噬在宫颈癌发生、发展过程中起到十分重要作用。mi RNA在宫颈癌细胞的增殖与凋亡、迁移与侵袭、肿瘤血管生成和肿瘤转移等过程中皆发挥重要作用。细胞自噬是细胞程序性死亡的一种,在肿瘤的不同阶段发挥了不同的作用,透射电镜下观察自噬小体的形成是判断自噬的金标准,同时mi RNA也调控着自噬小体形成的各个阶段。     

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.