FTY720通过miR-494/MST1抑制结肠癌细胞并增加吉西他滨敏感性的分子机制

背景结肠癌在我国恶性肿瘤中发病率和死亡率均居第5位,化疗是其主要治疗方式,有研究表明免疫抑制剂FT Y720对癌症细胞增殖起一定的抑制作用,抑制剂联合化疗药物可提高癌症治疗效果.本研究使用免疫抑制剂FTY720与吉西他滨联合处理结肠癌细胞,并探索miR-494/哺乳动物Ste20样激酶1 (mammalian Ste20-like kinase 1,MST1)对在此过程中对结肠癌细胞增殖和凋亡的影响,以期为结肠癌的治疗提供新的思路.目的研究FT Y720和吉西他滨对结肠癌细胞存活率和凋亡的影响和潜在的分子机制.方法用0.0001μg/mL、0.001μg/mL、0.01μg/mL、0.1μg/mL、1μg/mL的吉西他滨和2.5μmol/L、5μmol/L、7.5μmol/L、10μmol/L、12.5μmol/L的FTY720处理结肠癌SW1116细胞,CCK8法和流式细胞术检测SW1116细胞存活率和凋亡率,实时定量聚合酶链式反应检测miR-494和MST1 mRNA的含量,Western blot检测MST1、p21和Caspase-3蛋白表达水平,双荧光素酶报告系统验证miR-494与MST1的调控关系.结果吉西他滨(0.0001μg/mL、0.001μg/mL、0.01μg/mL、0.1μg/mL、1μg/mL)和FTY720 (2.5μmol/L、5μmol/L、7.5μmol/L、10μmol/L、12.5μmol/L)均可降低结肠癌SW1116细胞的存活率,且具有浓度依赖性,根据结果选取抑制率约为50%的0.1μg/mL吉西他滨和10μmol/L的FTY720进行后续实验,吉西他滨和FT Y720均可抑制细胞存活并促进细胞凋亡,且联合使用比单独使用效果更好;过表达miR-494可逆转FTY720、吉西他滨对SW1116细胞存活率和凋亡的作用;miR-494靶向调控MST1;抑制MST1可逆转FTY720和吉西他滨对SW1116细胞存活率和凋亡的影响.结论FTY720和吉西他滨通过miR-494/MST1抑制SW1116细胞存活,促进细胞凋亡.FTY720和吉西他滨对结肠癌SW1116具有抑制作用,且联合使用效果更佳.     

Successful prenatal management of two foetuses affected by antibodies against GP.Mur with prenatal genotyping analysis and a literature review

BackgroundGP.Mur belongs to the GP(B-A-B) hybrid glycophorin family, which is the most common hybrid glycophorin in Southeast Asia. Antibodies against GP.Mur may cause a clinically significant haemolytic disease of the foetus and newborn (HDFN) although, so far, not many cases have been reported in mainland China.Materials and methodsTwo Chinese women with a history of severe hydrops foetalis were seen in our centre. Alloantibody identification and GYP.Mur genotyping analysis were used for prenatal evaluation. Intrauterine transfusion was performed in two pregnancies in case 1. The features of these two women are described and literature-reported cases of HDFN related to antibodies against GP.Mur are summarised.ResultsThe phenotype of both mothers was Mi^a− Mur−, while the fathers’ was Mi^a+ Mur+ with a heterozygous GYP.Mur hybrid gene as determined by a high-resolution melting method of genotyping. In case 1, the antibodies against GP.Mur were detected in the mother’s serum and the cord blood of two foetuses. Fortunately, the latest foetus was successfully saved after intrauterine transfusion. In case 2, hydrops foetalis occurred in the first two pregnancies, but the risk of HDFN was excluded for the third foetus because of the GP.Mur negative phenotype. The literature review showed that 68.8% (11/16) of the reported cases of HDFN related to antibodies against GP.Mur occurred in the Chinese population, and that 37.5% (6/16) of them were cases of severe HDFN.DiscussionMore cases of severe HDFN caused by antibodies against GP.Mur are presumably undetected as GP.Mur cells are not included in the panel of obligatory screening tests in most Southeast Asian countries including mainland China. The high-resolution melting method for GYP.Mur genotyping and zygosity detection is helpful in prenatal management.     

胃癌中p14、p15、p16基因微卫星不稳定性的研究

 目的 对照检测伴有正常及高级别上皮内瘤变的胃腺癌组织中定位于染色体9p21区D9S166、D9S171、D9S941、D9S942和IFNA的微卫星不稳定性（MSI），探讨p14、p15和p16基因与胃癌发生发展的关系。方法 选择55例伴有正常及高级别上皮内瘤变的胃腺癌标本，应用手工显微切割、聚合酶链反应、高压凝胶电泳、硝酸银染色等技术, 对照分析正常、高级别上皮内瘤变和胃腺癌组织中9p21上的5个微卫星位点的MSI变化。结果 胃癌组织MSI总发生率为27 %（64／233），高级别上皮内瘤变MSI总发生率为18 %（42／233），正常组织中未发生MSI。胃癌组织中的MSI发生率显著高于高级别上皮内瘤变（P＜0.05）。在胃癌组织中，5个微卫星位点的MSI发生率依次为D9S171（45 %）、IFNA（41 %）、D9S941（22 %）、D9S166（16 %）、D9S942（15 %）；高级别上皮内瘤变组织中，依次为IFNA（22 %）、 D9S171（21 %）、D9S941（18 %）、D9S166（14 %）、D9S942（11 %）。在胃癌组织中D9S171位点的MSI发生率为45 %，在高级别上皮内瘤变的MSI发生率为21 %。两者差异有统计学意义（P＜0.05）。结论 胃癌中染色体9p21区发生有高频率的MSI，MSI 可能为胃癌发生过程中的早期分子事件，并且在胃癌发展过程中持续发挥作用。p14、p15和p16基因可能与胃癌的发生发展相关。     

米非司酮用于过期流产30例临床观察

目的：观察米非司酮用于过期流产的临床效果。方法：将米非司酮150mg顿服，并与己烯雌酚组对比，观察服药后组织自然排出率、宫颈松弛度、手术时间、术中出血量及清宫次数、组织物排出时间等指标，结果：米非司酮应用于过期流产后，宫颈松弛软化率高，缩短了手术时间，减少了术中出血量，有效地避免了过期流产者的凝血功能障碍，结论：米非司酮用于过期流产，能充分改善宫颈松弛度，缩短手术时间，减少手术中的出血量，此法简单易行，效果好，不良反应少.     

A Study on Nursing Students' Knowledge,Attitude, and Educational Needs for Brain-Death Organ Transplantation and Donation and Intent to Donate Organs

Objective

The purpose of this study was to identify the knowledge, attitude, educational needs, and will of nursing students on organ donation from brain-dead donors.

Neural localization of addicsin in mouse brain

Addicsin is a member of the prenylated Rab acceptor (PRA) 1 domain family and a murine homolog of the rat glutamate-transporter-associated protein 3-18 (GTRAP3-18). This protein is considered to function as a modulator of the neural glutamate transporter excitatory amino acid carrier 1 (EAAC1). However, its molecular functions remain largely unknown. Here, we examined the regional and cellular localization of addicsin in the central nervous system (CNS) by using a newly generated antibody specific for the protein. Distribution analysis by Western blot and immunohistochemistry demonstrated that the protein was widely distributed in various regions of the mature CNS, including the olfactory bulbs, cerebral cortex, amygdala, hippocampus CA1–3 fields, dentate gyrus, and cerebellum. Double immunofluorescence analysis revealed that addicsin was expressed in the somata of principal neurons in the CNS such as the pyramidal cells and gamma-aminobutyric acid (GABA)-ergic interneurons scattered in the hippocampal formation. Furthermore, the protein showed pre-synaptic localization in the stratum lucidum of the CA3 field of the hippocampal formation. Subcellular localization analysis of highly purified synaptic fractions prepared from mouse forebrain supported the cytoplasmic and pre-synaptic distribution of addicsin. These results suggest that addicsin has neural expression and may play crucial roles in the basic physiological functions of the mature CNS.     

Biochemical changes associated with the development and reversal of galactose cataracts.

The rate of synthesis of glutathione (GSH) in lens extracts during cataract formation has been determined and found to be the same as that of extracts from normal lenses. It is concluded that unlike X-ray-induced cataracts the potential mechanism for GSH synthesis in galactose cataracts is unaffected. In addition, the levels of GSH, free amino acids, dulcitol, cations and the degree of hydration of the lens during the development and reversal of galactose cataract have been determined.Feeding of a normal diet even after the development of mature cataracts (20 days) leads to the disappearance of cortical opacities almost completely leaving an essentially clear lens with only a very fine pinhead nuclear opacity.The levels of GSH, taurine and other free amino acids, which fall rapidly dudring cataract formation, return to near normal values during the reversal phase even though the lenses are hydrated. In cnntrast to the near complete recovery of these constituents, sodium ion concentration remains four times higher than in the control lenses almost 4 weeks after diet reversal. The recovery of potassium ion during the same period is about 70% of controls. The continued hydration of the lenses during the reversal phase of cataract, despite the disappearance of dulcitol, is apparently related to the elevated sodium ion concentration.A possible explanation for the recovery of GSH and free amino acids in hydrated lenses has been suggested.     

Nachweis einer Entspannungsfähigkeit bei verschiedenen Qigong-Übungen mittels Messung der Herz-Raten-Variabilität (HRV)

Introduction

The effects of qigong are changes in concentration and relaxation, following a dual principle, which will be demonstrated by measurement of heart rate variability (HRV).

Methods

HRV was measured in 4 female qigong teachers and 17 quigong practitioners (12 women and 5 men, mean age 47,9 years, SD 9,4 yrs), employing an ECG recorder (HeartMan®, Heart Balance Corp., Vienna). The sessions comprised exercises of daoistic qigong (n = 10) or chan mi gong (n = 11) and lasted for one to three hours.

Results

In different persons our HRV measurements showed identical phases of concentration and relaxation during the exercises as well as during intervals. While attentively listening to instructions as well as during Intervals all participants showed emotional and mental tension.

Conclusions

In this study, inter-individual differencesof relaxation could be demonstrated by HRV measurements In various subjects. Superior „competence” in Qigong did not matter. In fact specific qigong exercises may be applied as targeted tools for individual relaxation and as therapeutic options as well.     

米非司酮＋米索前列醇抗早孕药物流产的临床观察

目的：利用抗早孕药物米非司酮和米索前列醇达到终止妊娠的目的。方法：选取60例妊娠40—70天孕妇服用抗旱孕药物米非司酮和米索前列醇行药流术。结果：3例孕妇服用米非司酮即可流产,55例孕妇在使用前列腺素类药物后6小时内排出绒毛胎囊;2例孕妇在服药1周内排出。85％受术者能不清宫月经自行干净,15％受术者不清宫月经不能自行干净。