Alkylating DNA damage stimulates a regulated form of necrotic cell death

Necrosis has been considered a passive form of cell death in which the cell dies as a result of a bioenergetic catastrophe imposed by external conditions. However, in response to alkylating DNA damage, cells undergo necrosis as a self-determined cell fate. This form of death does not require the central apoptotic mediators p53, Bax/Bak, or caspases and actively induces an inflammatory response. Necrosis in response to DNA damage requires activation of the DNA repair protein poly(ADP-ribose) polymerase (PARP), but PARP activation is not sufficient to determine cell fate. Cell death is determined by the effect of PARP-mediated beta-nicotinamide adenine dinucleotide (NAD) consumption on cellular metabolism. Cells using aerobic glycolysis to support their bioenergetics undergo rapid ATP depletion and death in response to PARP activation. In contrast, cells catabolizing nonglucose substrates to maintain oxidative phosphorylation are resistant to ATP depletion and death in response to PARP activation. Because most cancer cells maintain their ATP production through aerobic glycolysis, these data may explain the molecular basis by which DNA-damaging agents can selectively induce tumor cell death independent of p53 or Bcl-2 family proteins.     

143例晚期喉癌患者的临床特征及生存分析

目的 总结143例晚期喉癌患者的临床特征,分析预后的影响因素。方法 回顾性分析2010年1月-2016年12月经中国人民解放军总医院治疗的143例晚期喉癌患者的临床资料。其中,男135例(94.4%),女8例(5.6%);年龄35~79岁,中位年龄58岁。依据患者治疗方案不同分为2组:手术联合术后放化疗组106例和非手术综合治疗组37例。收集患者基本临床情况、治疗、随访及生存情况;生存率及单因素生存分析采用Kaplan-Meier法和log-rank检验,多因素生存分析采用Cox比例风险回归模型。结果 143例晚期喉癌患者的5年总体生存率为67.9%。单因素分析显示,影响晚期喉癌患者预后的临床因素有年龄、临床分期、T分期及肿瘤分化程度等(P值均<0.05);Cox模型多因素分析显示,患者年龄、临床分期、肿瘤分化程度及治疗方式是影响预后的独立危险因素(P值均<0.05)。T₄期、临床Ⅳ期患者采用手术联合术后放化疗5年生存率分别为62.2%和59.5%,明显好于非手术综合治疗的18.2%和41.4%,差异均有统计学意义(P值均<0.05)。结论 晚期喉癌患者预后相对较差,影响患者预后的因素包括患者年龄、临床分期、肿瘤分化程度及治疗方式等。对于临床Ⅳ期、尤其是T₄期患者,采取手术联合术后放化疗可以获得相对较好的预后。     

三氧化二锑诱导急性早幼粒细胞白血病细胞凋亡的研究

目的 研究锑剂三氧化二锑（Sb2O3)对早幼粒细胞白血病细胞株NB4凋亡的诱导作用，以寻求早幼粒细胞白血病治疗的新方法。方法 采用细胞生长曲线，形态学及硝基四氮唑蓝（NBT）还原试验，判定NB4细胞的生长，分化及功能。采用细胞周期分析和DNA电泳研究细胞凋亡。结果 Sb2O3能诱导早幼粒白血病细胞凋亡，且具有时间，剂量依赖性。结论 Sb2O3能有效地诱导早幼粒白血病细胞凋亡，提示锑剂诱导细胞半亡的疗法，有望成为临床治疗早幼粒细胞白血病的新方法。     

Contrast Limited Adaptive Histogram Equalization image processing to improve the detection of simulated spiculations in dense mammograms

The purpose of this project was to determine whether Contrast Limited Adaptive Histogram Equalization (CLAHE) improves detection of simulated spiculations in dense mammograms. Lines simulating the appearance of spiculations, a common marker of malignancy when visualized with masses, were embedded in dense mammograms digitized at 50 micron pixels, 12 bits deep. Film images with no CLAHE applied were compared to film images with nine different combinations of clip levels and region sizes applied. A simulated spiculation was embedded in a background of dense breast tissue, with the orientation of the spiculation varied. The key variables involved in each trial included the orientation of the spiculation, contrast level of the spiculation and the CLAHE settings applied to the image. Combining the 10 CLAHE conditions, 4 contrast levels and 4 orientations gave 160 combinations. The trials were constructed by pairing 160 combinations of key variables with 40 backgrounds. Twenty student observers were asked to detect the orientation of the spiculation in the image. There was a statistically significant improvement in detection performance for spiculations with CLAHE over unenhanced images when the region size was set at 32 with a clip level of 2, and when the region size was set at 32 with a clip level of 4. The selected CLAHE settings should be tested in the clinic with digital mammograms to determine whether detection of spiculations associated with masses detected at mammography can be improved.Key Words: mammography, image processing, contrast limited adaptive histogram equalization, observer studies, breast cancer, spiculations     

Mouse homologues of the human AZF candidate gene RBM are expressed in spermatogonia and spermatids, and map to a Y chromosome deletion interval associated with a high incidence of sperm abnormalities

An RNA-binding motif (RBM) gene family has been identified on the human Y chromosome that maps to the same deletion interval as the 'azoospermia factor' (AZF). We have identified the homologous gene family (Rbm) on the mouse Y with a view to investigating the proposal that this gene family plays a role in spermatogenesis. At least 25 and probably >50 copies of Rbm are present on the mouse Y chromosome short arm located between Sry and the centromere. As in the human, a role in spermatogenesis is indicated by a germ cell-specific pattern of expression in the testis, but there are distinct differences in the pattern of expression between the two species. Mice carrying the deletion Yd1, that maps to the proximal Y short arm, are female due to a position effect resulting in non-expression of Sry ; sex-reversing such mice with an Sry transgene produces males with a high incidence of abnormal sperm, making this the third deletion interval on the mouse Y that affects some aspect of spermatogenesis. Most of the copies of Rbm map to this deletion interval, and the Yd1males have markedly reduced Rbm expression, suggesting that RBM deficiency may be responsible for, or contribute to, the abnormal sperm development. In man, deletion of the functional copies of RBM is associated with meiotic arrest rather than sperm anomalies; however, the different effects of deletion are consistent with the differences in expression between the two species.      

Interchromosomal duplications of the adrenoleukodystrophy locus: a phenomenon of pericentromeric plasticity

A 9.7 kb segment encompassing exons 7-10 of the adrenoleukodystrophy (ALD) locus of the X chromosome has duplicated to specific locations near the pericentromeric regions of human chromosomes 2p11,10p11, 16p11 and 22q11. Comparative sequence analysis reveals 92-96% nucleotide identity, indicating that the autosomal ALD paralogs arose relatively recently during the course of higher primate evolution (5-10 million years ago). Analysis of sequences flanking the duplication region identifies the presence of an unusual GCTTTTTGC repeat which may be a sequence-specific integration site for the process of pericentromeric- directed transposition. The breakpoint sequence and phylogenetic analysis predict a two-step transposition model, in which a duplication from Xq28 to pericentromeric 2p11 occurred once, followed by a rapid distribution of a larger duplicon cassette among the pericentromeric regions. In addition to facilitating more effective mutation detection among ALD patients, these findings provide further insight into the molecular basis underlying a pericentromeric-directed mechanism for non- homologous interchromosomal exchange.      

Cryopreservation of all prezygotes in patients at risk of severe hyperstimulation does not eliminate the syndrome, but the chances of pregnancy are excellent with subsequent frozen-thaw transfers

In-vitro fertilization patients (n = 15) at risk of ovarian hyperstimulation syndrome (OHSS) (oestradiol > or =4500 pg/ml on the day of human chorionic gonadotrophin administration and 25 or more follicles of intermediate or large size) underwent aspiration of all follicles and cryopreservation of all fertilized oocytes at the pronuclear stage. Patients were monitored for up to 2 weeks post- retrieval. Subsequent transfer of cryopreserved-thawed embryos was performed in programmed cycles using exogenous oestrogen and progesterone for endometrial preparation. Two patients (13%) developed OHSS necessitating hospitalization and vaginal aspiration of ascitic fluid. Two other patients (13%) developed moderate OHSS requiring ascitic fluid vaginal aspiration in the office setting, with dramatic improvement of the condition. Subsequent transfer of cryopreserved- thawed embryos yielded a clinical pregnancy rate of 58% per transfer and ongoing or delivery rates of 42 and 67% per transfer and per patient respectively. By eliminating pregnancy potential with cryopreservation of all prezygotes and examining the pregnancy potential with subsequent cryopreserved-thawed transfers, it is concluded that OHSS is reduced, but not eliminated for patients at risk. Subsequent transfer of cryopreserved-thawed prezygotes in a programmed cycle with exogenous steroids yields an excellent pregnancy rate.      

人era的结构特点分析及其定点突变体的构建

目的：构建最近克隆的人era基因的定点突变体。方法：利用数据库对era的结构特点进行分析，在此基础上用改良的重叠延伸法分别构建人EraN端和C端的定点突变体。结果：获得了分别针对人EraN端TGP结合结构域（位于29－36氨基酸残基）和C端具有RNA结合活性的 KH结构域（位于297－340氨基酸残基）的定点突变体。结论:人era定点突变体的构建为进一步的功能研究奠定了基础。     

骨组织工程种子细胞的研究进展

随着骨组织工程研究的进展 ,选择什么细胞作为其种子细胞成为近年来研究的热点。目前 ,骨组织工程应用中种子细胞有五种来源 :骨、骨膜、骨髓、骨外组织和早期胚胎。本文介绍了五种来源种子细胞的研究状况 ,并对种子细胞各自存在的问题及应用前景进行了分析。