An in-vitro Study on Reversing the Multidrug Resistance of Ovarioma by siRNA Regulated by hTERT Promoter

背景与目的：卵巢癌死亡率居妇科恶性肿瘤之首，化学药物治疗(化疗)耐药是造成患者总体预后不良的主要原因之一。mdr1基因及其表达产物P-gP被认为是引起多药耐药的主要原因。siRNA沉默技术是近年来兴起的一种新型的基因阻断技术。成功应用RNA干扰沉默mdr1逆转耐药采用RNA聚合酶Ⅲ启动子(H1，U6)表达经典的发夹结构RNA，缺乏组织细胞靶向性。本研究选择了具有组织特异性的hTERT启动子介导靶向mdr1的shRNA的表达，以期特异抑制mdr1表达从而逆转卵巢癌多药耐药。 方法： 1.通过利用Therom在线设计软件获得2个可识别不同位点的候选siRNA靶点序列，引用1个他人设计siRNA...Backgrouds & Objectives Ovarian carcinoma takes the first place in the mortality of all the gynecologic malignant tumors, one of the major reasons of the bad prognostics is the resistance of chemical therapy. The gene of mdr1 and its production P-gP are considered as the major factor of MDR. siRNA is a new technology to block gene expressing that has come up in recent years. Evidence has shown th...学位：医学硕士院系专业：医学院临床医学系_外科学学号：2452007115253

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目的 研究高危型人乳头瘤病毒（HR-HPV）感染相关的宫颈病变程度与抗人乳头瘤状病毒（HPV）抗体水平的相关性,探讨HPV致病的免疫学问题。方法 选取2012年1月-2013年6月在该院妇产科门诊就诊的女性中选取60例病理确诊为女性宫颈病变（CINⅠ及以上）,且宫颈脱落细胞的DNA检测为HR-HPV阳性者为研究组,根据组织学检测结果将研究组进一步分为低度病变组30例（CINⅠ）和高度病变组30例（CINⅡ或Ⅲ）。对照组为经核酸检测无HPV感染且病理诊断未见癌前病变的门诊患者60例,按年龄进一步分为低年龄组和高年龄组。低年龄组和高年龄组与低度病变组和高度病变组的年龄差异无统计学意义（P〉0.05）。分别抽取研究组及对照组外周血,检测其抗HR-HPV L1 Ig G抗体及中和抗体滴度,比较研究组与对照组抗体阳性率及抗体滴度水平的差别。结果 研究组血清中的抗HR-HPV L1 Ig G抗体阳性率及抗体滴度均高于对照组（P〈0.05）;低度病变组患者血清中的抗HR-HPV的中和抗体滴度高于相应对照组（P〈0.05）,而高度病变组的抗HR-HPV的中和抗体阳性率及抗体水平与相应对照组比较差异无统计学意义（P〉0.05）。结论 宫颈病变患者血清中抗HR-HPV L1 Ig G抗体升高,说明HPV感染可引起机体的体液免疫反应。低度病变组的中和抗体水平相对较高,可能是机体产生的中和抗体阻止了病毒的进一步感染。高度病变组的Ig G抗体和中和抗体均低下,说明进入CINⅡ/Ⅲ后HPV已经逃避了免疫系统的监视。基金项目：厦门市科技局项目（3502220124050）;2011年福建省科技计划项目资助计划,青年创新项目（20111）00310517

Involvement of restoration of cerebral blood flow and maintenance of eNOS expression in the prophylactic protective effect of a novel ferulic acid derivative FAD012 against ischemia/reperfusion injury in rats

Tissue plasminogen activator, aiming to restore cerebral blood flow (CBF), has been used for acute ischemic strokes in clinics; however, its narrow therapeutic time window remains a serious concern. To develop novel prophylactic drugs to alleviate cerebral ischemia/reperfusion injuries, ferulic acid derivative 012 (FAD012) was synthesized and showed comparable antioxidant properties to ferulic acid (FA) and probably possesses the potent ability to cross the blood–brain barrier. A more potent cytoprotective effect of FAD012 against H2O2-induced cytotoxicity in PC12 cells was also observed. In vivo toxicity was not observed in rats given a long-term oral administration of FAD012, indicating its good tolerability. A one-week-course oral administration of FAD012 significantly alleviated middle cerebral artery occlusion (MCAO)-induced cerebral ischemia/reperfusion injuries in rats, accompanied by the restoration of CBF and endothelial nitrogen oxide synthetase (eNOS) expression. Treatment with FAD012 significantly restored the cell viability and eNOS expression damaged by H2O2, used to mimic MCAO-triggered oxidative stress, in rat brain microvascular endothelial cells. Our findings suggested that FAD012 protected the viability of vascular endothelium and maintained eNOS expression, ultimately contributing to the restoration of CBF, and may provide a rationale for the development of FAD012 into an effective prophylactic drug for patients at high risk of stroke.p.18 Article number: 9663 Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)

A study of allopurinol in the prevention of recurrent calcium oxalate stones

1) 150例の再発性・特発性蓚酸カルシウム尿路結石症を対象として, 最低2年間を目標として, アロプリノール投与による結石再発予防の臨床的検討をおこなった.2)検討可能症例134例(男性113例, 女性21例, 平均年齢42.7歳)を, 結石の発生・再発様式により多発型23例とepisode型111例に分類し, 全例について結石の再発・増大の有無を, episode型については統計学的にも治療前後の再発率の検討をおこなった.3)全症例の結石再発・増大に関しては, 多発型23例中19例に再発・増大を認めず, 4例のみに増大を認めた.episode型111例については59例に再発を認めず, 52例に再発を認めた.134例全例を通じては78例(58.2%)に再発または既存結石の増大は認めず, 56例(41.8%)に再発・増大を認めた.4) episode型111例のアロプリノール投与前後の再発率を統計学的に比較した.111例全例の治療前後の再発率, 治療開始時に結石を有しなかった37例の治療前後の再発率, 治療前後2年間ずつの同期間の再発率を比較しえた79例のいずれにおいても, アロプリノール投与により再発率の有意の低下が観察されたWe studied the effect of allopurinol on the prevention of stone recurrence in 134 patients with recurrent, idiopathic calcium nephrolithiasis. They consisted of 113 male patients and 21 female, between 16 and 72 years with an average age of 42.7. The patients were divided into two groups according to the type of stone occurrence; those with multiple stones without previous stone episodes (multiple stone group), and the those with recurrent stones (stone episode group). Twenty three patients belonged to the multiple stone group and 111 patients belonged to the stone episode group. The stones in 19 of the 23 patients in the multiple stone group remained stable throughout the study, while stones in 4 grew. Fifty-nine of the 111 patients in the stone episode group were free from recurrence, but the others showed recurrence. Statistical analyses was done on the stone episode group. The stone recurrence rate of all of the 111 cases showed significant decrease during prophylactic treatment with allopurinol (p less than 0.01), although the observation period before treatment was 73.0 +/- 65.8 months and that during and after treatment was 28.2 +/- 12.1 months. During the two years before and after prophylaxis 79 patients also showed a significantly decreased recurrence rate. Moreover, regarding 37 cases without any stones at the start of treatment, stone recurrence rate decreased significantly after the administration of allopurinol. Throughout this study, we used a new method for evaluating reasonable stone recurrence. It did not calculate the number of stones recurred, but the stone-forming circumstance in each kidney.(ABSTRACT TRUNCATED AT 250 WORDS