DNA甲基化修饰在甲状腺癌中的研究进展

甲状腺癌是常见的内分泌系统恶性肿瘤,目前的研究发现甲状腺癌的发生与基因突变和表观遗传学改变有关.DNA甲基化是重要的表观遗传修饰之一,在调节甲状腺癌的进展中发挥着关键作用.随着表观遗传学研究的不断深入,DNA甲基化有望被开发为甲状腺癌诊断、预后和治疗应用方面的临床生物标志物.现对近年来DNA甲基化在甲状腺癌中的研究进展...     

乳腺癌的DNA甲基化研究进展

乳腺癌是严重威胁女性健康的疾病,其发病机制还不是很清楚。随着研究手段的不断提高,目前发现乳腺癌的发病机制不仅仅局限于基因突变、缺失等遗传学变化。随着表观遗传学的理论研究的深入,DNA甲基化在乳腺癌的病理生理过程中的作用逐渐被揭示。DNA甲基化是指经过DNA甲基转移酶的催化     

甲基化与弥漫大B细胞性淋巴瘤

表观遗传学是指在不改变DNA序列的情况下影响基因的表达模式,这种基因表达模式的改变一般发生在体细胞的增殖和发展过程中,并通过有丝分裂逐代传递,表观遗传包括至少两个方面,即DNA甲基化、组蛋白修饰。DNA甲基化作为表观遗传学的重要内容,与多种肿瘤的发生、发展密切相关。近年来的研究发现,弥漫大B细胞性淋巴瘤相关基因异常甲基化与弥漫大B细胞性淋巴瘤发生、发展、预后及药物反应密切相关。现就弥漫大B细胞性淋巴瘤中的甲基化研究进展予以综述。     

DNA甲基化与卵巢癌研究进展

卵巢癌是严重威胁女性健康的恶性肿瘤之一,由于缺少有效的早期诊断方法,其死亡率一直居妇科肿瘤之首。随着对卵巢癌发病机制的深入研究,人们认识到肿瘤的发生不仅与基因突变等遗传学机制有关,也与表观遗传学异常密切相关,其中DNA甲基化是表观遗传学机制最常见的形式。本文将对DNA异常甲基化在卵巢癌中的研究进展作一综述。     

XPO1基因突变的慢性淋巴细胞白血病临床特征及预后研究

目的：探讨携带exportin 1（XPO1）基因突变的慢性淋巴细胞白血病（chronic lymphocytic leukemia,CLL）患者的临床特征,为临床诊治提供线索。方法：回顾性分析2006年11月—2022年3月就诊于南京医科大学第一附属医院血液科、且检测出XPO1基因突变的CLL患者临床资料,比较初诊未治（treatment native,TN）和复发/难治（relapsed/refractory,R/R）XPO1突变患者的临床数据、治疗反应及生存结局。结果：在 543 例 CLL 患者中,15 例（2.8%）患者 XPO1 基因突变检测阳性,TN 组（368 例）、R/R 组（175 例）中患者的突变率分别为 9 例（2.4%）及 6 例（3.4%）,存在热点突变（E571K）。患者疾病分期多为 Rai Ⅲ/ Ⅳ期,Binet B/C组,且免疫球蛋白重链可变区基因（immunoglobulin heavy-chain variable region,IGHV）无突变。XPO1基因突变与NOTCH1、SF3B1、KMT2D、TP53等基因可同时出现,且与疾病状态无关,而TP53与XPO1基因突变同时发生多见于R/R组 （TN：11.1%;R/R：50.0%）。XPO1突变患者的中位至首次治疗时间（time to first treatment,TTFT）为1.8个月,中位无进展生存期 （progression-free survival,PFS）为19.8个月,中位总生存时间（overall survival,OS）为40.0个月;XPO1无突变组患者TTFT为8.1 个月,PFS为32.5个月,OS为49.8个月。结论：XPO1突变在CLL中为低频突变且常伴随其他基因突变同时发生。R/R患者携带XPO1突变多于TN患者,且肿瘤负荷更高。XPO1突变组患者的TTFT、PFS较XPO1无突变组患者趋向于更短。     

DNA甲基化与血液系统肿瘤的研究进展

肿瘤的研究，过去主要着眼于基因突变、缺失、染色体重排等遗传机制的改变，但是肿瘤的发生并非都可用癌基因突变学说加以解释。1983年Fcinberg等发现在肿瘤细胞中存在着基因总体低甲基化和局部高甲基化的现象。随着组蛋白修饰在肿瘤发生中的作用被发现，表观遗传修饰成为肿瘤发生机制研究的重要方向。所谓表观遗传（Epigcnetic）是指不涉及基因序列改变的可遗传的基因表达的变化，包括DNA甲基化和染色质结构的变化。     

甲基化与肿瘤的相关性研究

恶性肿瘤的发生是一个多因素、多阶段的复杂过程,涉及多种基因的功能异常.导致这些基因功能异常的原因包括基因突变、基因缺失、基因表观遗传学(epigenetic)改变等.在表观遗传学中,甲基化研究的最为深入,甲基化异常可导致基因表达的异常及基因组稳定性的降低,继而促进肿瘤发生和发展.近年来,DNA甲基化异常在肿瘤发生中所起的作用成为研究的热点.目前,在该领域的研究主要集中在甲基化在转录调控中的作用机制、甲基化检测对肿瘤的诊断和预后评估,以及应用甲基化抑制剂治疗肿瘤等方面.     

表观遗传学与疾病发生发展的研究进展

近年研究发现,表观遗传学会导致基因表达的持续性改变,它是疾病发生的重要机制。表观遗传学与众多疾病,包括肿瘤、糖尿病、神经精神疾病、自身免疫病、衰老、老年性疾病等的发生发展密切相关。表观遗传学主要有以下调控方式:DNA甲基化、组蛋白修饰、非编码RNA等机制。表观遗传学的研究将为研究疾病发生发展提供新视角,并为疾病临床治疗研究提供新方向和新思路。本文将对近年来表观遗传学研究进展作系统的综述。     

NOTCH1在CLL患者中的突变情况及预后价值

目的 应用二代测序技术检测新疆地区慢性淋巴细胞白血病(chronic lymphocytic leukemia,CLL)患者NOTCH1基因的突变情况,以及NOTCH1基因突变联合CLL-IPI预后评分系统对CLL患者的预后价值研究.方法 收集初治CLL患者67例,进行NOTCH1基因突变检测,比较其在不同预后分组CL...     

应用表观遗传学方法探索孕妇血浆中胎儿游离DNA

目的应用表观遗传学DNA甲基化技术从母血浆中检测胎儿DNA序列,扩大了非创伤性产前诊断的检测范围。方法随机选择早、中、晚期正常孕妇及非妊娠健康妇女各20名,以非妊娠妇女20名作为对照组。提取血浆中的游离胎儿DNA,应用表观遗传学DNA甲基化技术检测其目的基因u-maspin的表达水平,进行定性及相对定量,并对各期孕妇的样本均数进行对比式统计学分析。结果未甲基化maspin在非妊娠健康妇女血浆中未能检测到,在早、中、晚期孕妇血浆中的浓度随妊娠进展呈升高趋势。结论应用表观遗传学DNA甲基化技术从母血浆中检测妊娠期特异性表观遗传学标志物u-maspin可行,扩大了非创伤性产前诊断的检测范围。     

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.