miRNA-497与miRNA-195基因簇在宫颈癌组织中的表达及预测靶基因的生物信息学分析

目的探讨miRNA-497-195基因簇在宫颈癌组织中的表达,并对其预测的靶基因进行生物信息学分析,为miRNA-497-195基因簇在宫颈癌发生中的作用机制研究提供理论基础。方法收集2010年3月～2012年3月在广西壮族自治区人民医院就诊患者的宫颈标本,利用miRNA芯片技术检测宫颈病变组织中miRNA表达谱,用real-time RT-PCR进行验证;采用real-time RT-PCR检测miRNA-497和miRNA-195在宫颈病变组织中的表达情况,并用Spearman法进行miRNA-497与miRNA-195相关性分析。通过生物信息学预测miRNA-497和miRNA-195的靶基因,并对其靶基因进行GO（gene ontology）功能富集分析及信号转导通路富集分析。结果芯片结果显示,宫颈癌及高度鳞状上皮内瘤变中miRNA-195和miRNA-497表现为下调（均P〈0.05）。real-time RT-PCR结果显示,miRNA-497和miRNA-195在宫颈癌组织中表现为下调,且表达存在显著性相关（r=0.983,P〈0.05）。miRNA-497和miRNA-195预测靶基因大量重合,且集合功能也大量重合,并富集于细胞周期调控、生物学过程调控、转录调控、基因表达及核苷酸代谢过程等生物学过程,以及蛋白结合、核酸结合、蛋白激酶活性、连接酶活性等分子功能（P〈0.01）;KEGG通路分析涉及癌症通路、p53信号通路、GnRH信号通路、细胞外因子信号通路等信号传导通路及直肠癌、前列腺癌、甲状腺癌、黑色素瘤、慢性粒细胞性白血病、非小细胞肺癌等疾病通路（P〈0.05）。结论 miRNA-195和miRNA-497在宫颈癌组织中呈现低表达,二者表达呈显著正相关,miRNA-497-195基因簇可能是宫颈癌的抑制因子。miRNA-497和miRNA-195预测靶基因功能大量重合,并显著富集在与肿瘤发生相关的信号通路中。     

高尿酸通过miR-663下调转化生长因子β1抑制内皮细胞迁移

目的探讨高尿酸通过miR-663影响内皮细胞迁移功能的机制。方法培养人脐静脉内皮细胞系（EA．hy926）,用600μmol／L尿酸孵育48h,实时定量PCR检测miR-663的水平,并检测高尿酸患者血清中miR-663水平;利用双荧光素酶试验预测并验证miR-663的靶基因;检测高尿酸条件下内皮细胞中转化生长因子β1（transforming growth fator beta1,TGF—β1）的表达水平,利用miR-663抑制物、TGFB1siRNA转染及划痕实验观察高尿酸如何通过miR-663及其靶基因影响内皮细胞的迁移功能。结果高尿酸培养条件下内皮细胞中miR-663表达水平明显升高,高尿酸血症患者血清中miR-663的水平也高于正常人;双荧光素酶试验结果表明TGFB1的翻译水平受miR-663直接调控;高尿酸能明显抑制细胞的迁移能力,而高尿酸条件下TGF-β1的表达水平也明显下降,转染miR-663抑制物后,TGF-β1表达水平升高,内皮细胞迁移能力也明显改善,但是利用siRNA抑制TGF—β1的表达后,miR-663抑制物不能再促进内皮细胞的迁移。结论高尿酸通过miRNA-663下调TGF—β1而抑制细胞迁移。     

原发性胆汁性肝硬化患者血清中miR-132和miR-212的表达及意义

目的探讨原发性胆汁性肝硬化(PBC)患者血清中微小RNA-132(miR-132)和miR-212水平的变化及其临床意义。方法收集PBC患者、其他肝病患者和健康对照组各37例血清标本;用实时荧光定量聚合酶链反应(RT-qPCR)检测miR-132和miR-212的水平,并分析其与疾病严重程度的相关性。结果与健康对照组及其他肝病组比较,PBC患者血清miR-132和miR-212的水平显著降低(P均0.05)。PBC组血清miR-132与ALP、AST呈负相关(r=-0.67,r=-0.61,P均0.05);而血清miR-212与ALP、AST无相关性(r=-0.34,r=-0.25,P均0.05)。结论 miR-132和miR-212可能参与了PBC的发病机制,有望作为PBC的诊断和治疗靶点。     

miRNA-155对淋巴瘤的影响（英文）

淋巴瘤是血液系统肿瘤中最常见的一大类。在我国,霍奇金淋巴瘤占淋巴瘤的9%-10%,是一组疗效相对较好的恶性肿瘤;非霍奇金淋巴瘤占全部淋巴瘤病例的90%左右,并且近十几年来发病率逐年升高。近年来,人们逐渐发现,淋巴瘤的发生与miRNA有着极其密切的关系,miRNA在淋巴瘤的病理生理过程中所扮演的角色越来越引起人们的重视。本文主要介绍miRNA的家族成员之一,即miRNA-155,及其在弥漫性大B细胞性淋巴瘤、Bur-kitt淋巴瘤和霍奇金淋巴瘤中的作用机制,为今后对于淋巴瘤的治疗提供一些新的思路。     

Cimetidine-drug interactions

The use of cimetidine, the histamine H2 receptor antagonist, is associated with a relatively low incidence of adverse reactions. However, its liberal use has led to the identification of several clinically significant cimetidine-drug interactions that can lead to drug accumulation, toxicity, and life-threatening sequelae. A review of the literature and the clinical significance and physiologic basis of these interactions are presented. Recommended management of cimetidine-drug interactions is discussed.     

Extragonadal germ cell tumors of the head and neck region: review of 16 cases

During the period from 1928 to 1982, 16 children were treated or seen in consultation at the Children's Hospital Medical Center for extragonadal germ cell tumors of the head and neck region. Collectively, these tumors accounted for only 5 per cent of all benign and malignant germ cell tumors. Fourteen tumors were diagnosed in newborns and were classified as pure teratomas, either mature or immature. Six of these tumors were located in the cervical region, three presented within superficial facial structures, two were retro-orbital, and three arose within oropharyngeal or nasopharyngeal tissues. There were three endodermal sinus tumors, one of which appeared in an 11-month-old child who had undergone incomplete resection of an oropharyngeal teratoma as a newborn. Endodermal sinus tumors presented within the oropharynx, nasopharynx, and floor of the mouth and affected children at older ages (6 to 11 months). The overall prognosis for infantile teratomas of the head and neck region (exclusive of brain and spinal cord) is excellent, despite the presence of immature elements; however, tumor-related deaths can result from large unresectable primary tumors. The prognosis for children with endodermal sinus tumors remains guarded, with successful management depending on early diagnosis and aggressive adjuvant therapy.     

Abnormal biomechanics of feet and their cause of hyperkeratoses

A brief review of pedal anatomy and the mechanisms enabling feet to function as organs of locomotion is presented. The importance of the subtalar joint is emphasized. Four major abnormalities disturbing normal foot function are noted, and the most commonly encountered of these alterations, rearfoot varus, is discussed in some detail. A series of pedal abnormalities in rearfoot varus occurs because in the foot's attempt to overcome its imbalance, it pronates excessively and causes development of callus, corn, hallux valgus, and even ingrown toenail. Haglund's deformity, soft corn, and tailor's bunion are also secondary to the abnormality. Attempts to restrict the germinal compensatory pronation by various forms of padding of the medial aspect of the foot are frequently rewarded by restoration of asymptomatic feet. Surgical means of restoring normal function are briefly discussed.     

Severe, acute pulmonary disease in patients with systemic lupus erythematosus: ten years of experience at the National Institutes of Health

The sudden development of diffuse pulmonary infiltration in a patient with SLE presents difficult diagnostic and therapeutic problems to the clinician. In the past ten years, we have seen eight patients with this problem. Neither roentgenograms nor clinical findings were specific. In six patients, pulmonary hemorrhage was found, but in only two of them did it exist alone. In the other four, heart failure, uremia, and coagulopathy complicated the findings. In one patient, P carinii was the cause; in one congestive heart failure, which was not obvious clinically or radiologically, was the cause. Three patients died: one of uncomplicated pulmonary hemorrhage, one with pulmonary hemorrhage occurring during the treatment of pneumonia due to L bozemanii, and one with pulmonary hemorrhage and multiple complications including sepsis due to Candida. On the basis of this experience, we have recommended a plan of action for physicians facing this problem.