耐药性卵巢癌中CX43和P-gp的检测

目的:探讨细胞间隙连接蛋白43(connexin43,CX43)和P糖蛋白(P鄄Glycoprotein,P鄄gp)与上皮性卵巢癌化疗疗效(耐药或敏感)及临床病理的关系。方法:在1999年1月至2003年6月间,从临床资料及随访资料完整的卵巢癌病例中,筛选出60例原发上皮性卵巢癌(primaryepitheliaovariancarcinoma,PEOC)和6例正常卵巢的存档蜡块,作为研究对象。根据临床诊断将它们分为三组:化疗耐药组30例,化疗敏感组30例,正常卵巢组6例。这些病例术前均未接受过放疗,入院后均行全子宫和双附件切除 盆腔淋巴结清扫 阑尾切除 大网膜切除术,全部66例患者均有随访结果。用流式细胞术定量分析66例标本组织中CX43和P鄄gp蛋白的表达量。结果:①CX43蛋白的表达:化疗耐药组<化疗敏感组<正常卵巢组织,两两比较结果差异有统计学意义。②P鄄gp的表达:化疗耐药组>化疗敏感组>正常卵巢组织,差异均有统计学意义。结论:CX鄄43蛋白表达下降及P鄄gp蛋白的表达上升与上皮性卵巢癌的化疗耐药显著相关。     

上皮性卵巢癌ERCC1表达与顺铂化疗耐药的关系

目的 探讨切除修复交叉互补基因(ERCC1)在原发性上皮性卵巢癌顺铂化疗耐药中的意义.方法 用组织芯片仪制备组织芯片并结合免疫组织化学技术,检测56例上皮性卵巢癌病人癌组织中ERCC1蛋白的表达情况,并以38例正常卵巢组织作为对照,分析其与顺铂化疗耐药的关系,同时分析ERCC1在原发性上皮性卵巢癌中的表达与临床手术-病理分期(FIGO,2000)、病理学类型、分化程度、发病年龄、发生部位以及疾病发生的相关性.结果 38例正常卵巢组织中ERCC1阳性表达者17例(44.74%),56例上皮性卵巢癌组织ERCC1阳性表达者31例(55.36%),二者比较差异无显著性(χ2=1.022,P＞0.05).上皮性卵巢癌中ERCC1的表达与临床手术-病理分期、病理学类型、分化程度、发病年龄、发生部位及发病率均无明显的相关性(P>0.05).上皮性卵巢癌顺铂化疗耐药组ERCC1的阳性表达率为76.67%,明显高于敏感组的30.77%,差异有显著性(χ2=11.87,P<0.05).结论 上皮性卵巢癌ERCC1表达与顺铂化疗耐药相关.     

上皮性卵巢癌组织中PTEN和P-Akt 蛋白的表达及其临床意义

目的 探讨上皮性卵巢癌组织中PTEN和P-Akt蛋白的表达及其与临床病理参数的关系.方法 采用免疫组化方法分别检测25例正常卵巢组织、25例良性卵巢上皮性肿瘤、19例卵巢交界性肿瘤及69例卵巢上皮性癌组织中PTEN及P-Akt蛋白的表达状况,并分析其与卵巢癌主要临床病理参数之间的关系.结果 PTEN蛋白在正常卵巢组织与良性卵巢肿瘤组织中表达较高,在交界性卵巢肿瘤组织中表达开始下降,在上皮性卵巢癌中表达量最低,与前三组比较差异有统计学意义(P＜0.05),而P-Akt蛋白在各组中的表达趋势与PTEN相反,上皮性卵巢癌组与前三组比较差异有统计学意义(P＜0.05);PTEN蛋白表达在Ⅰ-Ⅱ期、高、中分化、淋巴结无转移的卵巢癌组织中分别高于Ⅲ-Ⅳ期、低分化、淋巴结有转移者,差异有统计学意义(P＜0.05),而P-Akt蛋白的表达趋势与PTEN相反,差异有统计学意义(P＜0.05).结论 与正常卵巢组织、良性卵巢肿瘤及交界性卵巢肿瘤比较,PTEN蛋白在上皮性卵巢癌中表达下调,而P-Akt蛋白表达上调,且卵巢癌不同分期、不同组织学分级及有无淋巴结转移之间蛋白表达水平不同,因此上皮性卵巢癌组织中PTEN和P-Akt蛋白的表达可能与卵巢上皮性癌的发生、发展及临床预后有关.     

MiR-130a 在上皮性卵巢癌铂类敏感与耐药患者血清中的表达及相关机制研究

目的 分析miR-130a在上皮性卵巢癌铂类敏感与耐药患者血清中的表达情况,探讨其耐药的相关机制。方法 选取32例上皮性卵巢癌铂类化疗耐药患者及30例化疗敏感患者,采用实时荧光定量PCR检测受试者血清中miR-130a表达差异,ELISA法检测血清中人第10号染色体缺失的磷酸酶及张力蛋白同源的基因(phosphatase and tensin homolog deleted on chromosome ten,PTEN)、B淋巴细胞瘤-2基因（B-cell lymphoma-2,BCL-2）表达情况。结果 耐药组患者血清miR-130a和BCL-2表达均高于敏感组,而PTEN表达低于敏感组（P均＜0.05）。且随着组织学分级增加及淋巴转移的发生,耐药组患者血清miR-130a表达量显著升高（P<0.05）。结论 MiR-130a可能通过抑制PTEN激活PI3K/AKT信号通路、上调BCL-2抑制肿瘤细胞凋亡参与上皮性卵巢癌铂类化疗耐药的产生,miR-130a有望成为逆转上皮性卵巢癌化疗耐药的基因治疗新靶点。     

间隙连接蛋白Cx43在卵巢癌中的表达及意义

目的：探讨间隙连接蛋白Cx43（connexin43,Cx43）在上皮性卵巢癌中的表达及意义。方法：对10例正常卵巢上皮，38例不同分化程度的卵巢浆液性囊腺癌的石蜡包埋切片，用免疫组织化学SP法和计算机图像分析系统检测Cx43蛋白的表达，结果：正常卵巢上皮及卵巢癌组织中Cx43蛋白定位于细胞膜和细胞质中；不同分化程度卵巢癌组织中Cx43阳性表达的相对面积和平均吸光度值均显著低于正常卵巢表面上皮细胞（P＜0．01），而且随着卵巢癌细胞分化程度的下降而显著降低（P＜0．01）。结论：Cx43蛋白表达下降与上皮性卵巢癌的发生发展密切相关。     

EPS8在卵巢浆液性腺癌中的表达分析

目的检测表皮生长因子受体通路底物8（epidermal growth factor receptor pathway substrate 8, Eps8）在卵巢浆液性腺癌组织、上皮性卵巢良性肿瘤及正常卵巢组织的表达,探讨Eps8在不同卵巢组织中的表达情况及在卵巢癌化疗耐药中的作用。方法采用免疫组织化学法检测76例卵巢浆液性腺癌（其中化疗敏感型40例,化疗耐药型36例）组织、15例上皮性卵巢良性肿瘤及15例正常卵巢组织中Eps8的表达情况,并分析其与卵巢癌化疗耐药间的关系。结果Eps8在卵巢浆液性腺癌组织中高表达,在上皮性卵巢良性肿瘤及正常卵巢组织中低表达,差异有统计学意义（P〈0．05）,但在化疗耐药型及化疗敏感型中的表达差异无统计学意义（P〉0．05）。结论Eps8在卵巢浆液性腺癌中高表达,其定位主要在细胞浆中,在化疗耐药型及化疗敏感型中的表达差异无统计学意义。     

p38MAPK在不同疗程化疗后卵巢癌中的表达及临床意义

目的 研究p38MAPK通路在不同化疗疗程上皮性卵巢癌中的表达及其与凋亡抑制蛋白Survivin、耐药相关蛋白(切除修复交叉互补基因1(ERCC1),肺耐药相关蛋白(LRP),谷胱甘肽转移酶(GST-π)表达的相关性及与预后的关系.方法 应用免疫组织化学方法检测P-p38、Survivin、ERCC1、LRP、GST-π在29例原发性卵巢上皮癌、30例复发性卵巢上皮癌和17例经新辅助化疗后行手术的卵巢上皮癌患者治疗前后标本的表达,并进行随访.结果 ①P-p38在原发性卵巢癌患者中的表达与新辅助化疗术后患者中阳性表达差异无显著性(P＞0.05),但明显高于复发性卵巢癌组(P＜0.01);Survivin、ERCC1、GST-πr在原发性卵巢癌患者中的表达与新辅助化疗术后患者中阳性表达差异无显著性(P＞0.05),但明显低于复发性卵巢癌组(P＜0.01).②新辅助化疗前后的自身配对标本中P-p38、Survivin、ERCC1、LRP、GST-π蛋白的表达情况均无显著性(P＞0.05).③P-p38与Survivin、ERCC1、LRP之间存在负相关性(P＜0.01),但与GST-π之间无相关性(P＞0.05).④P-p38阴性组平均生存时间短于阳性组平均生存时间,两组差异有显著性(P=0.006).结论①多疗程化疗可能通过抑制p38 MAPK通路而提高Survivin、ERCC1、LRP的表达导致上皮性卵巢癌铂类耐药的产生,而新辅助化疗并不能导致术后耐药机会的增加.②p38MAPK通路的激活可能改善铂类耐药患者的预后.     

脱嘌呤/脱嘧啶核酸内切酶与卵巢上皮性癌耐药相关性研究

目的 探讨脱嘌呤/脱嘧啶核酸内切酶(APE1)与卵巢上皮性癌耐药性的相关性以及其在卵巢癌化疗耐药中的作用机制.方法 应用免疫组织化学法对78例原发性卵巢上皮性癌组织和卵巢癌顺铂敏感株A2780、顺铂耐药株CP70中APE1的表达进行测定.结果 APE1在卵巢上皮性癌组织中呈胞核表达、胞浆表达或核浆共同表达.化疗敏感组和耐药组的APE1表达强度间差异有统计学意义(P=0.045),核表达者化疗敏感率与浆表达、核浆表达者比较差异有统计学意义(P=0.037).在卵巢癌顺铂耐药株CP70中APE1表达水平较顺铂敏感株A2780明显增高.结论 APE1表达强度和定位与以铂类为基础化疗药物的敏感性相关,时卵巢癌的化疗疗效有提示作用,检测APE1对前瞻性预测化疗药物敏感性和判断化疗疗效具有一定的临床指导价值.     

Notch3、pS6在上皮性卵巢癌组织中的表达及其与临床预后的关系

目的：探讨Notch3、pS6蛋白在上皮性卵巢癌组织中的表达及其与临床病理学特征及总生存期的关系。方法采用免疫组化法检测30例正常卵巢上皮组织、30例卵巢囊腺瘤以及120例上皮性卵巢癌组织中Notch3及pS6蛋白的表达。结果 Notch3、pS6蛋白在正常卵巢组织、良性卵巢囊腺瘤组织、上皮性卵巢癌组织中均有阳性表达,阳性率分别为16.7％、70.0％、91.7％和16.7％、76.7％、90.0％,上皮性卵巢癌中Notch3、pS6蛋白的表达显著高于正常卵巢组织及良性卵巢囊腺瘤组织（均 P＜0.01）,与临床分期、病理分级、组织类型、淋巴转移及腹水有关,与患者年龄无关。Notch3蛋白与pS6蛋白在上皮性卵巢癌中的表达呈正相关（rs＝0.668,P＜0.01）。Notch3及pS6高表达组总生存期较短,低表达组的总生存期明显较长（χ2＝41.479,P＜0.01）。Notch3和pS6高表达组腹水阳性率为82.1％,显著高于中表达组（51.9％）及低表达组（27.0％）（χ2＝28.448,P＜0.01）。结论上皮性卵巢癌组织中Notch3、pS6蛋白的高表达与患者生存期（不良预后）密切相关,高表达Notch3及pS6患者总生存期缩短。     

上皮性卵巢癌中Bax、Gal-3及GST-π表达与顺铂化疗耐药的关系

【摘要】 目的 探讨上皮性卵巢癌中细胞凋亡相关因子Bax、半乳糖凝集素-3（Gal-3）及谷胱甘肽转移酶-π（GST-π）表达与顺铂化疗耐药的关系。 方法 选取2018年4月～2019年12月黑龙江中医药大学附属第一医院收治的94例上皮性卵巢癌患者（卵巢癌组）为研究对象,按其对化疗是否敏感分为化疗敏感组（敏感组）58例和化疗耐药组（耐药组）36例。另选取同期进行健康体检的53例女性体检者作为对照组。比较各组Bax、Gal-3及GST-π表达情况及上述因子与上皮性卵巢癌病理特征的关系,并分析上述因子预测上皮性卵巢癌患者顺铂化疗耐药的价值。 结果 卵巢癌组Bax、Gal-3及GST-π阳性表达率均高于对照组,差异具有统计学意义 (P＜0.05)。Bax阳性表达率与上皮性卵巢癌患者临床分期、病理分级具有显著相关性 (P＜0.05);Gal-3阳性表达率与上皮性卵巢癌患者临床分期、淋巴结转移及病理分级具有显著相关性 (P＜0.05);GST-π阳性表达率仅与病理分级具有相关性 (P＜0.05)。敏感组Bax阳性表达率显著高于耐药组,Gal-3、GST-π阳性表达率显著低于耐药组,差异具有统计学意义 (P＜0.05)。ROC结果示： Bax、Gal-3及GST-π单项检测曲线下面积（AUC）分别为0.655、0.691、0.773,联合检测AUC为0.803,明显高于单独检测。 结论 Bax低表达、Gal-3及GST-π高表达与上皮性卵巢癌患者顺铂化疗耐药相关,联合检测上述因子可预测患者化疗的敏感性。     

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.