miR-302a对结直肠癌细胞奥沙利铂化疗敏感性的影响及机制

目的:探究miR-302a对结直肠癌细胞奥沙利铂化疗敏感性的影响及机制。方法:在四株结直肠癌细胞系HT29、HCT8、SW480、SW1463中,通过转染miR-302a mimic构建miR-302a过表达模型,RT-PCR检测过表达效果;CCK-8法检测转染48 h后高表达miR-302a细胞的增殖能力及对奥沙利铂的敏感性;蛋白质印迹法检测转染后P-gp蛋白及Wnt/β-catenin通路相关蛋白MMP-7、c-Jun、c-myc、β-catenin、LEF1的变化。结果:相比正常小肠上皮细胞HIEC,miR-302a在结直肠癌细胞系HT29、HCT8、SW480、SW1463中的表达较低。转染mimic后,miR-302a的表达明显上调（P<0.001）。增殖实验发现miR-302a的上调并不影响结直肠癌细胞的增殖,而在转染miR-302a的细胞中加入奥沙利铂,miR-302a组HT29、HCT8、SW480和SW1463细胞存活率相比miR-NC组分别降低2.46、1.89、2.39、2.86倍。进一步探究miR-302a增加奥沙利铂敏感性的机制,发现miR-302a可抑制P-gp蛋白的表达,并且抑制Wnt/β-catenin通路相关蛋白MMP-7、c-Jun、c-myc、β-catenin、LEF1的表达。结论:miR-302a可增加结直肠癌细胞奥沙利铂化疗敏感性,其机制可能是通过抑制P-gp的蛋白表达,并抑制Wnt/β-catenin信号通路相关蛋白表达而实现。     

Synergistic Interaction Between Dexmedetomidine and Ulinastatin Against Vincristine-Induced Neuropathic Pain in Rats

Antimicrotubulin chemotherapeutic agents such as vincristine (VCR), often induce peripheral neuropathic pain. It is usually permanent and seriously harmful to cancer patients' quality of life and can result in the hampering of clinical treatments. Currently, there is no definitive therapy, and many of the drugs approved for the treatment of other neuropathic pain have shown little or no analgesic effect. It is therefore vital to find new and novel therapeutic strategies for patients suffering from chemotherapeutic agent-induced neuropathic pain to improve patients' quality of life. This study shows that intrathecal injections of dexmedetomidine (DEX), or intraperitoneally administered ulinastatin (UTI) significantly reduces Sprague Dawley rats' mechanical allodynia induced by VCR via upregulation of interleukin-10 expression and activating the α2-adrenergic receptor in dorsal root ganglion (DRG). Moreover, when combined there is a synergistic interaction between DEX and UTI, which acts against VCR-induced neuropathic pain. This synergistic interaction between DEX and UTI may be partly attributed to a common analgesic pathway in which the upregulation of interleukin -10 plays an important role via activating α2-adrenergic receptor in rat dorsal root ganglion. The combined use of DEX and UTI does not affect the rat's blood pressure, heart rate, sedation, motor score, spatial learning, or memory function. All of these show that the combined use of DEX and UTI is an effective method in relieving VCR-induced neuropathic pain in rats.

术前访视在原发性高血压手术病人中的应用研究

目的探讨术前访视在原发性高血压手术病人中的应用价值.方法 60例原发性高血压手术病人随机均分为观察组和对照组.对照组病人采用常规护理,观察组病人在常规护理的基础上,于手术前1d下午进行术前访视,术时由访视护士负责接病人入手术室.比较两组入院时及术前的焦虑值、心率、收缩压和满意度.结果2组病人入院时的焦虑值、收缩压和心率,具有可比性,p＞0.05;观察组病人术前的各项观察指标均显著低于对照组,p＜0.05;且观察组病人的满意度高于对照组,p＜0.05.结论术前访视能有效缓解原发性高血压手术病人的焦虑情绪,维持其术中血压和心率的稳定,是保证此类病人顺利进行手术的有效护理措施.     

CD4+CD25+ T细胞在溃疡性结肠炎中的表达及其临床意义

目的 研究溃疡性结肠炎(UC)患者外周血CD 4CD 25调节性T细胞比例的变化,探讨其在UC病理机制中的意义.方法 选择UC患者33例,对照组20例.用流式细胞仪检测外周血CD 4CD 25T细胞阳性率.用RT-PCR检测外周单个核细胞(PBMC)中Foxp3 mRNA的表达.用酶联免疫吸附试验检测血清中IL-10和TGF-β的浓度.结果 UC患者CD 4CD 25T细胞占CD 4T细胞的比例明显低于对照组(P＜0.01),并且与疾病的活动指数及血沉水平均呈显著负相关(R值分别为-0.660和-0.572,P值均＜0.01).UC患者Foxp3 mRNA的表达也明显低于对照组(P＜0.01).两组患者血清IL-10和TGF-β的浓度比较无明显差异(P＞0.05).结论 UC患者外周血CD 4CD 25 调节性T细胞明显降低,与疾病活动性相关,提示这类细胞可能在UC的病理机制中发挥作用.Foxp3表达降低可能是导致CD 4CD 25 T细胞发育障碍的重要因素.     

丝裂原蛋白激酶抑制剂U0126对刚地弓形虫侵入宿主细胞的影响

目的观察丝裂原蛋白激酶(mitogenactivatedproteinkinases,MAPK)抑制剂对刚地弓形虫侵入宿主细胞的影响。方法以丝裂原蛋白激酶抑制剂U0126分别以不同浓度加入分孔培养的细胞中,于不同时间分别用吉氏染色和流式细胞仪(FCM)检测其宿主细胞感染速殖子的差异。结果吉氏染色检测在以U01261μM,10μM和100μM作用3小时下其感染率分别比对照组下降了20.22%(,P<0.01),52.91%(P<0.01)和75.27%(P<0.01);在作用6小时及9小时其感染率分别比对照组下降了32.88%(P<0.01),57.24%(P<0.01),79.21%(P<0.01)和41.26%(P<0.01),54.73%(P<0.01),80.80%(P<0.01)。FCM检测结果与之相似。结论U0126通过作用于MAPK信号传导途径而明显抑制弓形虫速殖子侵入宿主细胞。     

130例骨髓增生异常综合征的骨髓穿刺涂片和骨髓活检切片结果分析

目的：通过对130例骨髓增生异常综合征(MDS)患者的涂片和切片联合检测来观察两者的临床价值。方法：采用简易一步法抽吸——活检技术。在同一穿刺点先做抽取物涂片后，再做环钻活检。结果：粒系、巨核系病态造血检出率切片远高于涂片，而红系病态造血检出率切片低于涂片。结论：两种方法联合应用最大限度地减少MDS的漏诊率和误诊率。     

Multimerization and interaction of Toll and Spätzle in Drosophila

The Toll family of receptors is required for innate immune response to pathogen-associated molecules, but the mechanism of signaling is not entirely clear. In Drosophila the prototypic Toll regulates both embryonic development and adult immune response. We demonstrate here that the host protein Sp?tzle can function as a ligand for Toll because Sp?tzle forms a complex with Toll in transgenic fly extracts and stimulates the expression of a Toll-dependent immunity gene, drosomycin, in adult flies. We also show that constitutively active mutants of Toll form multimers that contain intermolecular disulfide linkages. These disulfide linkages are critical for the activity of one of these mutant receptors, indicating that multimerization is essential for the constitutive activity. Furthermore, systematic mutational analysis revealed that a conserved cysteine-containing motif, different from the cysteines used for the intermolecular disulfide linkages, serves as a self-inhibitory module of Toll. Deleting or mutating this cysteine-containing motif leads to constitutive activity. This motif is located just outside the transmembrane domain and may provide a structural hindrance for multimerization and activation of Toll. Together, our results suggest that multimerization may be a regulated, essential step for Toll-receptor activation.     

家族性易栓症合并儿童急性肺栓塞一例

患儿男,10岁,因“胸痛伴发热、吐血3 d”就诊于山东大学齐鲁儿童医院呼吸介入科,经过胸部查体、胸部CT、肺动脉造影、数字减影血管造影术、抗凝血酶活性检测、外显子组基因测序等检查,诊断肺动脉栓塞(双侧),家族性易栓症。临床上以胸痛、发热、气促为主要表现的肺栓塞患儿,不能以感染等常见原因解释的,需重点问询家族史,警惕家族性易栓症可能,应尽早基因检测,早诊断、早治疗对改善预后、减少并发症及病死率至关重要。     

降钙素原和C-反应蛋白在导尿管相关尿路感染早期诊断中的临床意义

目的:研究降钙素原(PCT)和C反应蛋白(CRP)在导尿管相关尿路感染(CAUTIs)早期诊断中的意义。方法:前瞻性观测疑诊CAUTIs患者88例,评价PCT和CRP对诊断CAUTIs的敏感性、特异性及相关性。结果:88例疑诊为CAUTIs患者中,根据中段尿细菌培养阳性结果分为2组,病例组65例,对照组23例,2组PCT和CRP水平差异有统计学意义(P0.05);PCT和CRP水平在CAUTIs诊断中ROC曲线下面积分别为0.898和0.743;对诊断CAUTIs的敏感度分别为83.1%、56.9%,特异度分别为82.6%、87.0%;PCT和CPR的相关系数为0.562(P0.01)。结论:PCT与CRP间具有正相关性,结合二者综合分析对于CAUTIs的早期诊断具有更好的临床价值。     

内质网应激介导的凋亡途径在大鼠酒精性脂肪性肝病中的变化及意义

目的研究内质网应激相关因子及其介导的凋亡途径在酒精性脂肪性肝病大鼠发病过程中的变化及意义。方法 Wistar大鼠40只随机分为正常组(8只)、模型组(酒精混合液喂养);模型组又分为4、8、12、16周4个时相点(各8只);采集标本后检测血清生化指标,观察肝脏病理组织学改变,对肝脏脂肪变程度和炎症活动度评分及肝组织中GRP78、SREBP1-c、Caspase-3蛋白表达及动态变化。结果与正常组比较,模型组大鼠第8周时肝组织中GRP78、SREBP1-c、Caspase-3蛋白表达开始升高,于16周时达最强,差异有显著统计学意义(P<0.01)。结论由GRP78、SREBP1-c、Caspase-3等相关调控因子介导的肝细胞内质网应激和凋亡反应途径参与了酒精性脂肪性肝病大鼠肝脏脂肪变性和炎症反应,并与酒精性脂肪性肝病发病机制关系密切。