子宫内膜癌中错配修复基因、CD4、Ki-67的表达及意义的研究

目的探讨子宫内膜癌中错配修复基因、CD4、Ki-67的表达及相互作用,为理解子宫内膜癌的发生发展、分子分型提供理论和实验依据。方法选择有完整临床病理资料的术前未经过放化疗及内分泌经治疗的散发性宫内膜样癌根治术后存档的腊块标本80例。应用免疫组织化学方法检测不同分级及分期肿瘤中的错配修复基因中四种主要蛋白MLH l、MSH2、MSH6和PMS2及CD4、Ki-67表达情况,探讨错配修复基因在散发性子宫内膜样癌中的表达和意义。结果 1.MMR表达缺失在子宫内膜样癌中的发生率为:21.25%,其中单个蛋白表达缺失14例,两个蛋白联合缺失3例。2.PMS2的缺失率最高,占41.18%(7/17),其次为MSH2和MSH6均为29.41%(5/17),MLH1缺失最为少,占17.65%。3.Ⅰ级病变中多数表现为单个MMR蛋白表达缺失,也可有2个蛋白组合的联合表达缺失,分别为MSH2/MSH6共缺失2例,MLH1/PMS2共缺失1例。Ⅱ级病变中仅检测到MMR单个蛋白表达缺失,未在Ⅲ级病变中检测到MMR表达缺失。4.MMR表达缺失主要发生于Ⅰ期及40岁以下患者,尤其以Ⅰa期患者多见。Ⅰa期患者常见的缺失类型为MSH6(4/9),40岁及以下的患者中MSH2为最常见的缺失类型,大于40岁的患者以PMS2的缺失最为常见。5.具有MMR表达缺失的子宫内膜样癌病例较无MMR表达缺失病例而言,有着更高的细胞免疫水平和更低的肿瘤细胞的增殖活性(P0.05)。结论 1.MMR参与了散发性子宫内膜样癌的发生发展,利用免疫组化方法可以很好的检测到组织中MMR的状态;2.PMS2和MSH2/MSH6共缺失是在子宫内膜样癌中的最常见的缺失类型;3.MMR表达缺失主要发生于Ⅰ期及40岁以下患者;4.MMR表达缺失提高了子宫内膜样癌患者的细胞免疫水平,降低了细胞增殖活性。     

前列腺癌DNA错配修复基因缺失的表达研究

为了探讨DNA错配修复基因（MMR）在前列腺癌中的表达及其意义，采用免疫组化方法检测11例前列腺癌患者的20份标本中错配修复基因MSH2，MLH1，PMS1和PMS2的表达，分析了其与前列腺癌发生与发展的关系。结果：这4种MMR基因在肿瘤区的表达都有不同程度的降低，PMS1在肿瘤细胞中大部分缺失或降低，在肿瘤区的表达率依次为MLH1＞MSH2＞PMS2＞PMS1。结论：在前列腺癌组织中PMS1和PMS2蛋白表达的丢失在MMR突变中是占主导的，其不同的丢失与前列腺癌的发生发展有关。     

子宫内膜癌患者微卫星不稳定性及其临床意义研究

背景子宫内膜癌是女性常见恶性肿瘤之一,近年来微卫星不稳定性在子宫内膜癌进展中的作用逐渐受到重视,但关于微卫星不稳定与子宫内膜癌患者临床病理特征及预后的关系研究较少见。目的分析子宫内膜癌患者微卫星不稳定性及其临床意义。方法选取2015年1月至2020年12月在湖北医药学院附属十堰市人民医院进行手术治疗的子宫内膜癌患者248例,收集其癌组织标本,采用免疫组织化学法检测MutL同源物1（MLH1）、MutS同源物2（MSH2）、MutS同源物6（MSH6）、减数分裂后分离蛋白（PMS2）表达情况。分析微卫星不稳定性与子宫内膜癌患者临床病理特征及预后的关系。结果子宫内膜样腺癌患者MLH1、MSH2、MSH6、PMS2表达缺失率分别为32.6%（78/239）、22.2%（53/239）、2.9%（7/239）、65.7%（157/239）;子宫内膜鳞癌患者MLH1、MSH2、MSH6、PMS2表达缺失率分别为5/5、3/5、5/5、4/5;子宫内膜透明细胞癌患者MLH1、MSH2、MSH6、PMS2表达缺失率分别为4/4、2/4、3/4、2/4。不同病理类型子宫内膜癌患者MLH1、MSH2、MSH6、PMS2表达缺失率比较,差异有统计学意义（P<0.05）。子宫内膜样腺癌患者高微卫星不稳定性（MSI-H）、低微卫星不稳定性（MSI-L）、微卫星稳定性（MSS）发生频率分别为19.7%（47/239 ）、34.7%（83/239）、45.6%（109/239）;子宫内膜鳞癌患者MSI-H、MSI-L、MSS发生频率分别为4/5、1/5、0;子宫内膜透明细胞癌患者MSI-H、MSI-L、MSS发生频率分别为3/4、1/4、0。不同病理类型子宫内膜癌患者MSI-H、MSI-L、MSS发生频率比较,差异有统计学意义（P<0.05）。不同年龄、肿瘤分化程度子宫内膜癌患者MSI-H、MSI-L、MSS发生频率比较,差异无统计学意义（P>0.05）;不同肌层侵犯深度子宫内膜癌患者MSI-H、MSI-L、MSS发生频率比较,差异有统计学意义（P<0.05）。MSI-H、MSI-L、MSS子宫内膜癌患者总生存期、无病生存期的Kaplan-Meier生存曲线比较,差异无统计学意义（P>0.05）。Cox比例风险模型分析结果显示,错配修复蛋白（MMRP）表达情况是子宫内膜癌患者总体生存情况的独立影响因素（P<0.05）,但并非无病生存情况的独立影响因素（P>0.05）。结论微卫星不稳定性与子宫内膜癌患者病变进展及预后有关,检测微卫星不稳定性对子宫内膜癌的临床防治有一定参考价值。     

PTEN、P53与子宫内膜癌发病关系研究

目的 研究抑癌基因PTEN、P53在子宫内膜中的表达,探讨其临床意义.方法 采用免疫组化法,对正常子宫内膜、子宫内膜增生过长、子宫内膜不典型增生各20例,子宫内膜癌50例及子宫内膜癌旁组织50例中PTEN及P53的表达进行检测.结果 PTEN在正常子宫内膜、子宫内膜增生过长、子宫内膜不典型增生、子宫内膜癌旁组织及子宫内膜癌中表达缺失率逐渐上升,P＜0.05,差异有显著性.P53蛋白表述在子宫内膜癌中阳性率达44%,P＜0.01,差异有极显著性.结论 PTEN、P53二者皆为抑癌基因,皆参与子宫内膜癌的发生、发展.     

错配修复（MMR）蛋白（MLH1、PMS2、MSH2和MSH6）表达与子宫内膜癌临床病理特征和预后相关性分析

目的 分析错配修复(MMR)蛋白表达与子宫内膜癌临床病理特征和预后相关性。方法 选取我院2018年2月至2020年5月收治的70例子宫内膜癌(UCEC)患者,采用免疫组化法对4种蛋白(MLH1、PMS2、MSH2和MSH6)表达情况进行检测,并将4种MMR蛋白中1种及以上表达缺失判定为错配修复基因缺陷(d MMR),全部阳性则判定为错配修复基因完整(p MMR)。检测UCEC患者MMR蛋白缺失情况并对其与病理特征的关系进行分析。结果 4种MMR蛋白表达均定位于肿瘤细胞核,可作为内对照;d MMR组与p MMR组年龄、病理组织学类型、临床分期及淋巴结转移等比较,差异有统计学意义(P0.05),表现为dMMR组发病年龄低、肿瘤分期低、淋巴结转移少见。结论 dMMR子宫内膜癌比例较低,且MLH1和PM52蛋白表达缺失与MSH2和MSH6相比较为多见。MLH1和PMS2、MSH2和MSH6常协同表达或缺失。MMR蛋白与UCEC临床病理特征关系密切。MMR蛋白对预测UCEC的恶性程度、临床预后及UCEC发病机制方面有指导意义。     

子宫内膜癌中抑癌基因PTEN突变与微卫星不稳定性的相关性分析

 目的探讨子宫内膜癌中抑癌基因PTEN突变和微卫星不稳定性(MSI)之间的关系,以及可能的发生机制。方法应用PCR方法检测实验组中5个微卫星位点的微卫星不稳定性;应用聚合酶链反应-单链构象多态性分析法(PCR-SSCP)和DNA序列分析法,检测40例子宫内膜癌和22例子宫内膜不典型增生、23例正常子宫内膜组织中PTEN第5、第8外显子突变情况,并进行突变测序。结果PTEN的突变在正常子宫内膜、子宫内膜不典型增生和子宫内膜癌中,表达差异有显著性(P<0.05);在子宫内膜不典型增生中,PTEN突变已经有了显著性的改变;PTEN基因突变与子宫内膜癌的手术病理分期有关(P<0.05);2例(2/11,18.2%)DNA测序发现PTEN突变发生在PTEN外显子8的poly(A)区域;子宫内膜癌中抑癌基因PTEN突变与微卫星不稳定性(MSI)高度相关(χ2=18.06,P<0.01)。结论PTEN突变和微卫星不稳定性是I型子宫内膜癌中重要的分子事件,二者在内膜癌中高度相关。可能存在由于MSI导致PTEN核苷酸重复序列突变增加的致癌途径。     

子宫内膜癌hMSH2及PTEN蛋白的异常表达

[目的]探讨错配修复基因hMSH2及抑癌基因PTEN异常表达在子宫内膜癌发生中的意义。[方法]采用免疫组织化学SP法检测62例子宫内膜癌和16例子宫内膜增生过长组织hMSH2及PTEN蛋白的表达情况,率的差异比较采用卡方检验。[结果]子宫内膜癌与子宫内膜增生过长组hMSH2蛋白的阳性表达率为64.52%与18.75%,两组差异显著(P<0.05);PTEN蛋白表达缺失率为64.52%与50.00%,差异不显著(P>0.05)。PTEN蛋白表达缺失与子宫内膜癌组织分化程度及患者年龄不相关(P>0.05);PTEN蛋白的表达缺失率在hMSH2蛋白阳性表达组为70.00%,高于阴性表达组的54.55%,但差异不显著(P>0.05)。[结论]抑癌基因PTEN的错配可能是子宫内膜癌发生的原因。     

抑癌基因PTEN在子宫内膜癌组织中的表达

目的:研究抑癌基因PTEN在子宫内膜癌的表达,探讨其在子宫内膜癌发生、发展中的作用.方法:用免疫组化方法检测PTEN在50例子宫内膜癌、20例子宫内膜不典型增生、20例正常子宫内膜组织中的表达.结果:PTEN在正常子宫内膜、子宫内膜不典型增生、子宫内膜癌中的表达率分别为100%、80%、46%,其中子宫内膜癌与正常子宫内膜差异有显著性(P<0.05).PTEN表达与子宫内膜癌的手术分期、肌层浸润有关(P<0.05).结论:PTEN在子宫内膜癌发生、发展中可能起一定作用,并可能成为早期诊断的一项有用指标.     

DNA错配修复基因甲基化在H446细胞获得性耐药中的作用

目的 探讨DNA错配修复基因MLH1（human MutL homolog 1）、MSH2（human MutS homolog2）甲基化在人小细胞肺癌H446细胞获得性耐药中的作用。方法 RT—PCR及Western blot法检测H446细胞及其多药耐药细胞H446／DDP中MLH1、MSH2基因的mRNA表达和蛋白表达,甲基化特异性PCR（MSP）法检测MLH1、MSH2基因启动子CpG岛甲基化状态。结果 H446／DDP细胞中MLH1、MSH2基因的mRNA及蛋白水平均较H446细胞显著降低（P〈0．01）,且其启动子甲基化程度明显增强。结论 DNA错配修复基因MLH1、MSH2启动子甲基化诱导其表达下调可能是人小细胞肺癌获得性耐药的重要机制之一。     

PTEN、P27在子宫内膜癌中的表达及其临床意义

目的:探讨抑癌基因PTEN与细胞周期调控因子P27在子宫内膜癌中的表达,探讨其临床意义。方法:采用免疫组化法对正常子宫内膜、子宫内膜增生过长、子宫内膜不典型增生各20例,子宫内膜癌50例及子宫内膜癌旁组织50例中PTEN及P27的表达进行检测。结果:PTEN在正常子宫内膜、子宫内膜增生过长、子宫内膜不典型增生、子宫内膜癌旁组织及子宫内膜癌中阳性表达率逐渐下降,P27在子宫内膜癌中阳性率为34%。PTEN、P27皆与组织学分级有关(P<0.01)。结论:PTEN基因失活和P27蛋白缺乏参与了子宫内膜癌的发生、发展,而且与癌细胞的分化有关。     

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.