A hybrid protein of the amino-terminal fragment of urokinase and mutant plasminogen activator inhibitor-2 efficiently inhibits tumor cell invasion and metastasis

The urokinase plasminogen activator(uPA) system plays important roles in tumor cell invasion and metastasis. In the present study, we evaluated the effects of ATF-PAI2CD, a hybrid protein of the amino-terminal fragment of urokinase and mutant plasminogen activator inhibitor-2, on 95D cells in vitro and in vivo. Furthermore, our results support a current hypothesis that fusion protein blocks tumor invasion and motility by inhibiting localized pericellular proteolysis. Treatment of 95D cells with ATF-PAI2CD resulted in a dose-dependent decrease in tumor-cell invasion through matrigel, and ATF-PAI2CD was much more effective than PAI-2CD. In addition, extracellular regular protein kinase (ERK1/2) expression was downregulated and the adhesion ability to fibronectin was increased in 95D cells treated with the fusion protein, which was confirmed by cell adhesion assay. A high-concentration of ATF-PAI2CD caused a significant reduction in tumor volume and weight in BALB/c (nu/nu) mice female inoculated with human 95D cells (5×10⁶); the antitumor effects were significant, which demonstrated a 67.9±4.2% reduction in tumor growth compared with control mice. The number of lymphatic metastasis was significantly reduced in mice treated with high- and middle- concentrations of ATF-PAI2CD, whereas a low-concentration of ATF-PAI2CD failed to exhibit any antimetastatic effects. In conclusion, the results suggested that the hybrid protein has therapeutic potential for lung carcinoma and other tumors to inhibit tumor invasion and metastasis.     

Effect of RAGE and its ligands on CD4+ T cells北大核心CSCD

RAGE (receptor for advanced glycation end products) is a multiligand receptor on the cell surface. Ligand-RAGE interactions activate several signal transduction pathways that propagate cellular oxidative stress and inflammatory response. RAGE expressed on the CD4+ T cells has been identified as a central transduction receptor which affects the activation, proliferation, migration and differentiation of the cells. In addition, blockade of RAGE suppressed the development of multiple immune-related disorders mediated by CD4+ T cells. These studies highlight the importance of RAGE and its ligands for CD4+ T cells. This article briefly reviews the role of RAGE and its ligands on the proliferation, migration and differentiation of CD4+ T cells and summarizes the related research progress.     

Targeting protein arginine methyltransferase 5 inhibits colorectal cancer growth by decreasing arginine methylation of eIF4E and FGFR3

Protein arginine methyltransferases (PRMTs) plays critical roles in cancer. PRMT5 has been implicated in several types of tumors. However, the role of PRMT5 in cancer development remains to be fully elucidated. Here, we provide evidence that PRMT5 is overexpressed in colorectal cancer (CRC) cells and patient-derived primary tumors, correlated with increased cell growth and decreased overall patient survival. Arginine methyltransferase inhibitor 1 (AMI-1)strongly inhibited tumor growth, increased the ratio of Bax/Bcl-2, and induced apoptosis in mouse CRC xenograt model. AMI-1 also induced apoptosis and decreased the migratory activity in several CRC cells. In CRC xenografts AMI-1 significantly decreased symmetric dimethylation of histone 4 (H4R3me2s), a histone mark of type II PRMT5, but not the expression of H4R3me2a, a histone mark of type I PRMTs. These results suggest that the inhibition of PRMT5 contributes to the antitumor efficacy of AMI-1. Chromatin immunoprecipitation (ChIP) identified FGFR3 and eIF4E as two key genes regulated by PRMT5. PRMT5 knockdown reduced the levels of H4R3me2s and H3R8me2s methylation on FGFR3 and eIF4E promoters, leading to decreased expressions of FGFR3 and eIF4E. Collectively, our findings provide new evidence that PRMT5 plays an important role in CRC pathogenesis through epigenetically regulating arginine methylation of oncogenes such as eIF4E and FGFR3.     

高职护生考试前心理状态调查

预防和增进心理健康，是提高高职护生综合素质的重要内容。为了解高职护生考试前的心理状况，对491名在校高职护生进行了问卷调查，现将结果报告如下。     

PCR and oligonucleotide array for detection of Enterobacter sakazakii in infant formula

Enterobacter sakazakii has been implicated in a several form of neonatal meningitis with a high mortality rate. In the present study, the species-specific PCR and oligonucleotide array assays were developed to detect the 16S-23S rDNA internal transcribed spacer (ITS) of E. sakazakii. Two pairs of specific PCR primers and 10 oligonucleotide probes were designed by sequencing the ITS of six strains of E. sakazakii and BLAST of GenBank. The specificity and efficiency of the PCR and oligonucleotide array methods were tested against a panel of numerous strains from 88 different bacterial strains. All of the E. sakazakii strains generated positive signal, and no cross-reaction was observed with non-E. sakazakii strains in the PCR and oligonucleotide array detections based on ITS sequences. Sensitivity of the detections is 1.3 CFU/100 g infant formula with the selective enrichment. Both of the PCR and oligonucleotide array procedures take only 48 h including the enrichment culture, whereas the conventional methods required at least 5 days. This study demonstrated that both of the pathogenic detections are time-saved and reliable.     

Surgical treatment of complex spinal cord lipomas

Purpose

This paper shows the long-term benefits of total/near-total resection of complex spinal cord lipomas and meticulous reconstruction of the neural placode, and specifically, its advantage over partial resection, and over non-surgical treatment for the subset of children with asymptomatic virgin lipomas.

Methods

The technique of total resection and placode reconstruction, together with technical nuances, are described in detail. We added 77 patients with complex lipomas to our original lipoma series published in 2009 and 2010, to a total of 315 patients who had had total or near-total resection and followed for a span of 20 years. Long-term outcome is measured by overall progression-free survival (PFS) with the Kaplan–Meier analysis, and by subgroup Cox proportional recurrence hazard analysis for the influence on outcome of 4 predictor variables of lipoma type, presence of symptoms, prior surgery, and post-operative cord–sac ratio. These results are compared to an age-matched, lesion-matched series of 116 patients who underwent partial lipoma resection over 11 years. The results for total resection is also compared to two large published series of asymptomatic lipomas followed without surgery over 9 to 10 years, to determine whether prophylactic total resection confers better long-term protection over conservative treatment for children with asymptomatic lipomas..

Results

The PFS after total resection for all lipoma types and clinical subgroups is 88.1 % over 20 years versus 34.6 % for partial resection at 10.5 years (p?<?0.0001). Culling only the asymptomatic patients with virgin (previously unoperated) lipomas, the PFS for prophylactic total resection for this subgroup rose to 98.8 % over 20 years, versus 67 % at 9 years for one group of non-surgical treatment and 60 % at 10 years for another group of conservative treatment. Our own as well as other published results of partial resection also compare poorly to non-surgical treatment for the subset of asymptomatic virgin lipomas. Multivariate subgroup analyses show that cord–sac ratio is the only independent variable that predicts outcome, with a 96.9 % PFS for ratio <30 % (loosest sac), 86.2 % for ratio between 30 and 50 %, and 78.3 % for ratio >50 % (tightest sac), and a threefold increase in recurrence hazard for high ratios (p?=?0.0009). Pre-operative patient profiling using multiple correspondence analysis shows the ideal patient for total resection is a child less than 2 years old with a virgin asymptomatic lipoma, who, with a PFS of 99.2 %, is virtually cured by total resection.

Conclusion

Total/near-total resection of complex lipomas and complete reconstruction of the neural placode achieves far better long-term protection against symptomatic recurrence than partial resection for all lesions; and for the subset of asymptomatic virgin lipomas, also better than non-surgical treatment. Partial resection in many cases produces worse outcome than conservative treatment for asymptomatic lesions.     

800型肠内营养泵在结肠癌根治术后病人中的应用及护理研究

对于外科结肠癌根治术后的病人,术后肠道营养至关重要,我科2007年4月-2008年1月收治结肠癌根治术后的病人60例,术后6 h应用800型肠内输液泵开始输注能全力,能够按时、按质、按量完成营养液的输注,病人能够很好地接受,应用营养泵后病人胃肠道功能恢复快,没有出现腹泻、急性机械肠梗阻,肠瘘和代谢性并发症,理想的肠内营养泵不会增加术后并发症[1], 现将其介绍如下.     

50例尿道会师牵引术病人的护理

[目的]探讨临床护理在减少尿道会师牵引术并发症中的作用.[方法]回顾性分析50例尿道会师牵引术病人的护理,并与外院相同病人的并发症发生率做对比.[结果]50例病人中,10例发生尿道狭窄,行定期尿道扩张术,随诊1年排尿正常;2例发生暂时性尿失禁;3例发生阳痿,6个月后恢复;其余35例无并发症发生.[结论]加强尿道会师牵引术病人的护理有助于降低手术并发症的发生.     

黄五漱口液对化疗所致口腔炎预防效果观察

目的：观察黄五漱口液含漱对恶性肿瘤患者化疗所致口腔炎的预防效果。方法：将肿瘤化疗患者189例随机分为甲、乙、丙3组，甲组63例用黄五漱口液含漱，乙组60例用朵贝尔氏液含漱，丙组66例不做处理，观察3组患者的口腔炎发生率及口腔炎构成。结果甲、乙、丙3组口腔炎发生率分别为4．76％，16．67％，24．24％；甲、乙两组比较x^2＝4．61，P＜0．05；乙、丙两组比较x^2=1.10，P＜0．05；甲、丙两组比较x^2＝9．74，P＜0．01。结论：黄五漱口液含漱能更有效地预防口腔炎的发生。     

Effect of smoking on serum concentrations of total homocysteine and B vitamins in mid-pregnancy

There are conflicting findings in the literature on the effect of smoking on total homocysteine (tHcy) concentrations in non-pregnant subjects. We evaluated the effect of smoking on serum concentrations of tHcy, folate, vitamin B-12 pyridoxal 5'-phosphate (PLP, a coenzyme form of vitamin B-6) in 196 women at 18 and 30 weeks' gestation. The smokers were defined as those who self-reported cigarette smoking and had serum concentrations of thiocyanate, a biomaker of smoking, in the highest quartiles of the population. Mid-pregnancy serum tHcy concentrations were not significantly different between smokers and non-smokers. Folate, vitamin B-12 and PLP concentrations were generally lower in smokers than non-smokers. In smokers, tHcy concentrations had significant negative correlations with folate at both time points. The multiple regression analyses indicated that serum folate concentration was the most significant factor associated with tHcy concentrations among smokers, whereas thiocyanate concentrations showed no such effect. We conclude that serum tHcy concentrations were most strongly associated with the nutritional status of folate among the B vitamins tested during mid-pregnancy in our subjects. We suggest that it is essential to consider the nutritional status of folate, vitamin B-12 and vitamin B-6 in evaluating the effect of smoking on homocysteine metabolism.