胃泌素瘤的诊断与治疗

胃泌素瘤(Gastrinoma)一种具有分泌胃泌素功能的肿瘤,以胰腺非β细胞瘤所致高胃酸分泌和顽固性溃疡为特征的临床综合征。其临床表现为胃液、胃酸分泌过多,高胃泌素血症,多发、非典型部位难治性消化性溃疡和     

乳腺癌靶向治疗药物研究进展

乳腺癌是女性常见的恶性肿瘤之一,其发病率高居女性肿瘤疾病首位,全世界每年约有50万妇女死于乳腺癌。目前对于乳腺癌的治疗主要有手术、放疗、化疗和内分泌治疗等4种手段。近年来,随着对恶性肿瘤发病的基因和分子机制研究的不断深入,针对致癌基因的分子靶向治疗技术被应用于医学临床。分子靶向治疗是以肿瘤细胞中特有的基因片段为治疗位点,通过调节或阻断这些基     

Enhance tumor radiosensitivity by intracellular delivery of eukaryotic translation initiation factor 4E binding proteins

PTEN (phosphatase and tensin homologue deleted on chromosome ten)/PI3K (phosphatidylinositol 3-kinase)/Akt/mTOR (mammalian target of rapamycin) signaling pathway, which is commonly dysregulated in a broad array of human malignancies, controls the assembly of eukaryotic translation initiation factor 4F (eIF4F) complex through regulation of eIF4E binding proteins (4E-BPs) phosphorylation. And accumulated data over the past two decades implicated eIF4F complex as one of the promising targets for anticancer therapy. It has been confirmed that the translation initiation of mRNA coding for hypoxia-inducible factor-1α (HIF-1α) and survivin, which had been considered as the two major determinants of tumor radiosensitivity, are both controlled by eIF4F complex. Also, eIF4F complex controls the expression of VEGF and bFGF, the two well-known pro-angiogenic factors involved in developing radioresistance. Therefore eIF4F complex plays a pivotal role in regulation of radiosensitivity. In this article, we postulate that cell-permeable, phosphorylation-defective 4E-BP fusion proteins, which could be prepared by substituting the mTOR recognition motif located in N-terminal of 4E-BPs with protein transduction domain from HIV-1 TAT, HSV-1 VP22 or PTD4, could not only inhibit tumor growth but also enhance tumor response to radiation therapy through disruption of eIF4F complex assembly. In our opinion, the recombinant fusion proteins are superior to mTOR inhibitors for they do not cause immunosuppression, do not lead to Akt activation, and could be easily prepared by prokaryotic expression. If the hypothesis was proved to be practical, the cell-permeable, phosphorylation-defective 4E-BP fusion proteins would be widely used in clinical settings to improve tumor response to radiotherapy in the near future.     

Suppression of autophagy by FIP200 deletion inhibits mammary tumorigenesis

Autophagy is a conserved cellular process for bulk degradation of intracellular protein and organelles in lysosomes. In contrast to elegant studies of beclin1 using mouse models and cultured cells demonstrating a tumor suppression function for autophagy, knockout of other essential autophagy proteins such as ATG5, ATG7, or FIP200 (FAK family-interacting protein of 200 kDa) in various tissues did not lead to malignant tumor development in vivo. Here, we report that inhibition of autophagy by FIP200 ablation suppresses mammary tumor initiation and progression in a mouse model of breast cancer driven by the PyMT oncogene. Deletion of FIP200 resulted in multiple autophagy defects including accumulation of ubiquitinated protein aggregates and p62/SQSTM1, deficient LC3 conversion, and increased number of mitochondria with abnormal morphology in tumor cells. FIP200 deletion did not affect apoptosis of mammary tumor cells or Ras-transformed mouse embryonic fibroblasts (MEFs), but significantly reduced their proliferation in both systems. We also observed a reduced glycolysis and cyclin D1 expression in FIP200-null mammary tumor cells and transformed MEFs. In addition, gene profiling studies revealed significantly elevated expression of interferon (IFN)-responsive genes in the early tumors of FIP200 conditional knockout mice, which was accompanied by increased infiltration of effector T cells in the tumor microenvironment triggered by an increased production of chemokines including CXCL10 in FIP200-null tumor cells. Together, these data provide strong evidence for a protumorigenesis role of autophagy in oncogene-induced tumors in vivo and suggest FIP200 as a potential target for cancer therapy.     

LMP1 antagonizes WNT/β-catenin signalling through inhibition of WTX and promotes nasopharyngeal dysplasia but not tumourigenesis in LMP1(B95-8) transgenic mice

Latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) can induce cell transformation and tumourigenesis, but the mechanism is not understood. Previous studies have suggested that LMP1 acts through up-regulation of cellular proliferation pathways including the Wnt/β-catenin pathway, in which β-catenin is the central effector. Increased levels of β-catenin coupled with a decrease in E-cadherin lead to reduced cell adhesion. This pathway is antagonized by WTX (Wilms' tumour gene on the X chromosome), which can promote the ubiquitination and degradation of β-catenin. In the present study, we established L2/LMP1B(95 - 8) /EGFP transgenic mice to investigate the in vivo role of LMP1. Down-regulation of WTX and E-cadherin was accompanied by increased expression of β-catenin in these mice. Even though invasive tumours did not develop, dysplasia was seen in the nasopharynx and oropharynx epithelium of these transgenic mice. Analysis of LMP1(+) , WTX(+) , and LMP1 siRNA silenced HNE-1 cell lines demonstrated that WTX could exert a dominant role in LMP1-mediated WNT/β-catenin pathway regulation. This study indicates that LMP1 antagonizes the WNT/β-catenin pathway by inhibiting WTX, and this reduction in WTX is associated with epithelial dysplasia via regulation of the WNT/β-catenin pathway molecules E-cadherin and β-catenin. Further studies are required for a better understanding of the relationship between LMP1-mediated antagonization of the WNT/β-catenin pathway and tumourigenesis.     

Significance of hemolysis on extracorporeal life support after cardiac surgery in children

Hemolysis is common during extracorporeal life support (ECLS). Elevated levels of circulating plasma free hemoglobin (FHb) has been linked to the development of hemoglobinuria nephropathy. Its clinical significance in patients receiving ECLS remains unknown. Medical records of 104 children <3 years old who required ECLS after repair of congenital heart disease were reviewed. Forty-two patients required continuous renal replacement therapy (CRRT) during ECLS (CRRT group), and 62 patients did not (no-CRRT group). For all patients, FHb level and the degree of fluid overload at the end of ECLS predicted the mortality rate during ECLS. Compared with the no-CRRT group, the CRRT group had a higher mortality rate during ECLS, a higher peak FHb level during ECLS, a higher FHb level at the end of ECLS, and more days of ECLS. In the CRRT group, the FHb level at the end of ECLS predicted death during ECLS. In the no-CRRT group, the peak FHb level was associated with a worse renal function. In conclusion, elevated FHb levels were associated with renal dysfunction and death during ECLS in children undergoing cardiac surgery. Further studies are needed to elucidate the cause–effect relationship in our findings.     

干血片标本放置时间对葡萄糖-6-磷酸脱氢酶活性的影响

目的 通过分析标本不同保存时间对葡萄糖-6-磷酸脱氢酶(G6PD)活性的影响,探讨G6PD缺乏症合适的标本储存时间,保证实验检测的准确性.方法 免疫荧光法测定G6PD值,测定放置不同时间段的G6PD酶活性,对干血片标本在不同的时间内筛查数据结果进行比较,选择合适的存放时间及条件.结果 标本放置4℃冰箱9 d内检测G6PD活性差异无显著性(P>0.05),而9 d后G6PD活性明显下降(P<0.05).结论 G6PD活性测定时,干血片标本制备放置4℃冰箱保存后建议在9 d内完成检测.     

后路选择性内固定矫形治疗青少年特发性脊柱侧凸

目的 评价经后路选择性关键椎体内固定矫形治疗青少年特发性脊柱侧凸（AIS）的临床疗效,探讨其手术适应证。方法经后路选择性关键椎体内固定矫形治疗的131例青少年AIS患者,术前均进行详细的临床和影像学检查评估,按影像学资料确定主侧凸顶椎、端椎、中立椎、稳定椎等关键椎体,并拟定关键椎体椎弓根螺钉内固定。结果主侧凸Cobb角由术前的平均51．3°±12．9°矫正至术后的平均8．9°±4．5°。131例均获得随访,时间8～52个月,末次随访时主侧凸Cobb角平均丢失4．6°±1．2°,椎弓根螺钉松动1例,未发现椎弓根螺钉及棒的断裂。结论经后路选择性关键椎体内固定矫形治疗青少年AIS可取得良好的临床疗效,减少患者医疗费用,符合我国实际国情,但术前应做好适应证选择。     

结直肠手术下腹正中切口全层与分层缝合技术比较

目的比较结直肠手术下腹正中切口全层缝合与分层缝合技术应用的切口愈合能力差异。方法回顾性比较1998-2000年和2007-2008年间两组各65例患者,分析丝线分层缝合关腹和可吸收双股缝线全层关腹组的数据源,比较两种材料和方法条件下切口愈合率和并发症。结果全层缝合组手术耗时明显比分层缝合少（6．31±0．58min vs9．58±0．95min）。切口一期愈合和甲级愈合率两组间无显著差异,脂肪液化（3．07％vs15．38％）、切口感染（3．07％vs9．24％）和切口裂开（1．54％vs13．85％）等近期并发症和慢性窦道（1．54％vs7．69％）等远期并发症比较差异显著（P〈0．05）。全层缝合组无切口疝发生,分层缝合组2例切口疝,两组间比较无统计学差异（P〉0．05）。结论全层连续缝合技术较之分层缝合对预防结直肠手术下腹正中切口感染和裂开等效果显著,“宽对合”是防止术后切口急性和后期并发症的关键技术。     

米力农治疗充血性心力衰竭的临床疗效观察

目的：观察米力农对充血性心力衰竭患者的临床疗效。方法：应用米力农治疗充血性心力衰竭患者140例,观察治疗前后心功能级别变化,并进行超声心动图指标测定。结果：应用米力农治疗后超声心动图测定显示SV、CO、EF、FS、E峰较治疗前明显增加（P〈0.01）,A峰明显下降（P〈0.05）,LVD、RVD、LAD显著缩小（P〈0.05）,心功能改善138例,总有效率为98.6%。结论：米力农能改善心脏收缩、舒张功能,且有扩张血管的作用,对充血性心力衰竭患者有明显疗效。