营养与表观遗传学基因组印记关系的研究进展

表观遗传修饰中印记基因的异常不仅影响胚胎发育,还可诱发出生后的发育异常。早期营养可能改变基因印记的调节,而饮食是影响健康的重要因素,且与肿瘤关系密切。本文概括表观遗传学基因组印记和其在肿瘤发生中的作用机制及研究情况,详述食物营养与表观遗传学基因组印记的关系及研究技术,并对其未来的研究方向进行预测。     

人类胚胎发育、精子发生与DNA甲基化关系的研究进展

表观遗传是指基因的核苷酸序列不发生变化,但基因表达却发生了可遗传的改变。DNA甲基化是表观遗传重要的调控机制,它参与了动物胚胎发育、基因印迹和X染色体失活等过程,在基因表达的调控中具有重要作用。DNA甲基化可引起基因组中相应区域染色质结构变化,使染色质高度螺旋化,凝缩成团,失去转录活性。现对DNA甲基化与人类胚胎发育与精子生成的关系等进行综述。     

衰老的表观遗传修饰研究

衰老是内、外因素共同作用的结果,是一种多基因的复合调控过程,衰老相关基因的表达调节衰老的进程。表观遗传修饰包括DNA甲基化和组蛋白乙酰化等,是基因表达调控的重要方式之一。衰老过程中表观遗传修饰改变复杂,通常基因组脱氧甲基胞苷(dmC)的含量普遍减少,而在某些启动子含GC丰富序列的局部区域(称为CpG岛)dmC的含量增加[1]。因此表现为细胞衰老时出现总基因组DNA甲基化水平下降和某些特异基因的高甲基化[2]。现就衰老相关基因的表观遗传修饰改变及其在衰老过程中的作用作一综述。一、表观遗传修饰与基因调控(一)DNA甲基化DNA甲基…     

胚胎干细胞或诱导性全能干细胞自我更新和分化机制研究进展

“211工程”三期建设遗传发育与生殖医学重点学科建设的子项目——胚胎干细胞或诱导性全能干细胞定向分化机制的研究,在2008-2011年建立了着床后人胚胎早期发育的全基因组表达谱式;揭示了calcineurin/NFAT信号通路对细胞谱系决定的调控机制;揭示以Oct4为核心的胚胎干细胞命运决定的分子调控机制,其中包括发现并系统研究了对胚胎干细胞自我更新起重要作用的转录因子Oct4的蛋白质翻译后修饰;揭示Oct4的重要合作蛋白Sox2的蛋白质翻译后修饰及在胚胎干细胞中的作用;发现共激活因子p300直接调控胚胎干细胞中Nanog的表达及调控机制;发现Oct4新的下游基因Stk40并揭示Stk40在胚胎干细胞中的功能及作用机制;首次提出核仁蛋白在胚胎干细胞自我更新维持中的重要作用.2011年“胚胎干细胞及早期胚胎发育的分子调控机制研究”项目获得教育部高等学校科学研究优秀成果奖——自然科学奖二等奖.     

精子发生过程中的组蛋白变化与雄性不育

男性不育的许多病理现象与生精细胞的表观遗传改变关系密切。表观遗传在精子发生过程中调控着生精细胞的有丝分裂、减数分裂和精子形成过程,其中,作为表观遗传的一个重要研究内容——组蛋白,在精子发生过程中会发生多位点和多种形式的氨基酸残基修饰,不同的修饰方式在精子发生的不同阶段精确地调控着生殖细胞的发育过程,且在精子形成阶段发生鱼精蛋白和组蛋白的替换。此外,在精子发生过程中,组蛋白修饰的异常改变还可能会损伤精子的发育过程,导致雄性不育。本文总结了精子发生过程中组蛋白修饰的变化、对生殖细胞发育的调控作用,以及组蛋白的异常改变与雄性不育的关系。     

DNA甲基化与组蛋白修饰对克隆胚发育的影响

在正常的受精、发育过程中,基因组DNA不对称的去甲基化、重新甲基化以及组蛋白修饰作用发生在整个受精和胚胎发育过程中.本文将从DNA甲基化、DNA不对称的去甲基化和组蛋白修饰作用就其原理,相互之间的关系及其对胚胎发育情况的影响作以综述,并对近年来,DNA甲基化与组蛋白修饰作用在胚胎发育过程中的研究作以总结.     

干细胞分化的表观遗传调控

干细胞具有自我更新能力和多谱系细胞分化能力,在基础医学和临床应用中有极大研究意义。以胚胎干细胞为模型,近年来干细胞分化的表观遗传调控已成为研究热点。染色质结构的表观遗传调控,比如DNA甲基化、翻译后组蛋白修饰,对于胚胎发育时基因的激活和抑制非常关键。本文综述了干细胞多潜能性维持和干细胞分化的表观遗传机制及其一些表观遗传修饰之间的联系。     

表观遗传与肿瘤代谢研究进展

表观遗传学主要关注DNA甲基化、组蛋白修饰、染色质重塑,以及非编码RNA等超越DNA序列的基因调控机制。表观遗传机制参与了个体发育、细胞命运决定和肿瘤发生等众多生物学过程。其中表观遗传信息以各种染色质修饰和高级结构的形式存储于基因组中,它的建立和维持与细胞代谢紧密相关。肿瘤细胞中存在的代谢改变包括有氧糖酵解、葡萄糖摄取量增加、谷氨酰胺代谢异常活跃、利用非主要供能物质供能等,这些改变满足了肿瘤发生发展过程中旺盛的能量和物质需求,帮助细胞适应缺氧的肿瘤微环境,进而为肿瘤增殖、侵袭、迁移等生物活动提供支持。肿瘤细胞的表观遗传修饰与代谢之间存在复杂的相互关系,一方面肿瘤细胞中的代谢产物作为表观修饰酶的辅因子、修饰供体或拮抗分子影响表观修饰景观;另一方面表观遗传修饰可以直接改变代谢酶和转运蛋白的表达或通过影响信号转导和转录因子的表达调控细胞代谢。本文综述了不同表观遗传学过程与肿瘤细胞代谢之间的相互作用,并展望两者在肿瘤治疗中的潜在应用前景。     

遗传和表观遗传机制在先天性心脏病中的研究进展

先天性心脏病是胎儿期心脏及大血管发育异常所致的先天性畸形,是最常见的出生缺陷之一。先天性心脏病病因复杂,染色体异常、基因突变、核酸修饰、非编码RNA等遗传和表观遗传机制在其发生过程中发挥重要作用。现阶段,染色体异常、基因突变等遗传机制已经广泛应用于临床疾病的诊断与治疗。然而,针对遗传及表观遗传修饰在先天性心脏病的诊疗应用仍需深入研究。本文综述了染色体异常、基因突变、拷贝数变异及表观遗传修饰与先天性心脏病发生的关系,以期为进一步探究先天性心脏病早期诊断及个体化治疗提供依据。     

m6A甲基转移酶复合物在肿瘤发生、发展中的作用研究进展

表观遗传转录组学在肿瘤发生、发展中起到了重要的调节作用，而N6-甲基腺苷（m6A）修饰是RNA最常见的一种表观遗传学修饰方式，其在甲基转移酶复合物和去甲基化酶的调控下维持着动态平衡状态。早期的研究表明m6A在胚胎发育、神经发生、DNA损伤、应激反应等生理过程中扮演着重要的角色，而近年的研究证实其在肿瘤发生、发展中也起到了重要的调控作用。本文就m6A甲基转移酶复合物在肿瘤发生、发展中的作用研究进展作一综述。     

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.