Heparanase-1 is downregulated in chemoradiotherapy orbital rhabdomyosarcoma and relates with tumor growth as well as angiogenesis

AIM:To determine the role of heparanase-1(HPSE-1)in orbital rhabdomyosarcoma(RMS),and to investigate the feasibility of HPSE-1 targeted therapy for RMS.METHODS:Immunohistochemistry was performed to analyze HPSE-1 expression in 51 cases of orbital RMS patients(including 28 cases of embryonal RMS and 23 cases of alveolar RMS),among whom there were 27 treated and 24 untreated with preoperative chemoradiotherapy.In vitro,studies were conducted to examine the effect of HPSE-1 silencing on RMS cell proliferation and tube formation of human umbilical vein endothelial cells(HUVECs).RD cells(an RMS cell line)and HUVECs were infected with HPSE-1 sh RNA lentivirus at a multiplicity of infection(MOI)of 10 and 30 separately.Real-time PCR and Western blot were applied to detect the m RNA and protein expression levels of HPSE-1.Cell viability of treated or control RD cells was evaluated by cell counting kit-8(CCK-8)assay.Matrigel tube formation assay was used to evaluate the effect of HPSE-1 RNAi on the tube formation of HUVECs.RESULTS:Immunohistochemistry showed that the expression rate of HPSE-1 protein was 92.9%in orbital embr yonal RMS and 91.3%in orbital alveolar RMS.Tissue from alveolar orbital RMS did not show relatively stronger staining than that from the embryonal orbital RMS.However,despite the types of RMS,comparing the cases treated chemoradiotherapy with those untreated,we have observed that chemoradiotherapy resulted in weaker staining in patients’tissues.The expression levels of HPSE-1 declined significantly in both the m RNA and protein levels in HPSE-1 sh RNA transfected RD cells.The CCK-8 assay showed that lentivirus-mediated HPSE-1 silencing resulted in significantly reduced RD cells viability in vitro.Silencing HPSE-1 expression also inhibited VEGF-induced tube formation of HUVECs in Matrigel.CONCLUSION:HPSE-1 silencing may be a promising therapy for the inhibition of orbital RMS progression.     

Influence of ethanol on the metabolism of alprazolam.

Background: Alprazolam is a commonly used benzodiazepine in clinical practice, and when coingested with ethanol, alprazolam can increase behavioral irritability and aggression. However, the mechanism of its interaction with ethanol remains unknown.

Research design and methods: The pharmacokinetics of alprazolam was studied in vivo in rat experiments involving the simultaneous administration of alprazolam and ethanol, and the interactions between ethanol and alprazolam were investigated in vitro in human liver microsomes. In silico molecular docking was applied to analyze the change in the CYP3A4–alprazolam-binding conformation when ethanol was coadministered with alprazolam.

Results: Compared with alprazolam administered alone (2 mg/kg), the C_max of alprazolam increased when ethanol was simultaneously administered at 3 g/kg. The concentrations of alprazolam significantly increased by 39%, 17%, 105%, and 642% at 5, 10, 30, and 120 min intervals in the brain when coadministered with ethanol, respectively. Molecular docking results suggested that the conformation of CYP3A4 with alprazolam changed when ethanol was bound to the SER119 residue, which seems critical in the process of CYP3A4–alprazolam binding.

Conclusions: Ethanol might increase the toxicity of alprazolam by inhibiting the activity of CYP3A4, although other pharmacokinetic processes may be affected. Ethanol could change the conformation of CYP3A4 and affect alprazolam binding.     

Frailty and Clinical Outcomes in Advanced Heart Failure Patients Undergoing Left Ventricular Assist Device Implantation: A Systematic Review and Meta-analysis

Background

Frailty has been identified as a risk factor for adverse clinical outcomes after cardiac intervention or surgery. However, whether it increases the risk of adverse outcomes in patients undergoing left ventricular assist device (LVAD) therapy has been controversial. Therefore, we conducted a systematic review and meta-analysis of the frailty measures and clinical outcomes of length of stay and mortality in this setting.

Compound composite odontome associated with impacted canine. Case report

A case of compound composite odontome is reported. The classification and aetiology of odontomes is briefly discussed.     

Pivotal role of mast cell carboxypeptidase A in mediating protection against small intestinal ischemia–reperfusion injury in rats after ischemic preconditioning

Aim of the study

Mast cell (MC) degranulation contributes to the protection mediated by ischemic preconditioning (IPC); however, the precise mechanisms underlying this protection remain largely unknown. Mast cell carboxypeptidase A (MC-CPA) is released solely from MCs and plays a critical role in degrading toxins and endothelin 1 (ET-1). The present study sought to explore whether MC-CPA is involved in the process of IPC in a rodent model of small intestinal ischemia reperfusion (IIR) injury.

Materials and methods

IIR injuries were induced in Sprague–Dawley rats by clamping the superior mesenteric artery for 60 min followed by reperfusion for 2 h. One cycle of 10 min intestinal ischemia and 10 min of reperfusion was used in the IPC group, and the MC stabilizer cromolyn sodium and MC potato carboxypeptidase inhibitor were administered before the start of IPC. At the end of experiment, intestine tissue was obtained for assays of the MC-CPA3, tumor necrosis factor-α, interleukin-6, and ET-1 contents and myeloperoxidase activities. Intestinal histologic injury scores and MC degranulation were assessed. Apoptosis indices and cleaved caspase- 3 protein expressions were quantified.

Results

IIR resulted in severe injury, as evidenced by significant increases in injury scores and MC-CPA3, tumor necrosis factor-α, interleukin-6, and ET-1 contents that were accompanied with concomitant elevations in cleaved caspase 3 expression, apoptosis indices, and myeloperoxidase activities. IPC induced a significant increase in MC-CPA3, induced MC degranulation, and attenuated IIR injury by downregulating IIR-induced biochemical changes, whereas cromolyn sodium and potato carboxypeptidase inhibitor abolished the IPC-mediated changes.

Conclusions

These data suggest that IPC protected against IIR injury via the MC degranulation-mediated release of MC-CPA.     

应用辅助沟通系统促进自闭症儿童语言和沟通能力的发展

目的:以文献研究的方法探讨应用计算机和电子技术进行图片及符号与语言转换的辅助沟通技术对自闭症儿童沟通和语言能力所起的作用。资料来源:应用计算机检索CNKI,台湾中文期刊服务网和台湾博硕士论文信息网在1997-01/2006-12与自闭症和辅助沟通相关的文章,限定文章语言种类为中文,检索词“辅助沟通、自闭症、语言”;同时检索ProQuest Psychology Journals、Education Resources Information Center和Medline在1997-01/2006-12期间相关的文章,限定文章语言种类为“English”,检索词“Augmentative and alternative communication、autism、language”。并查询与语言和沟通障碍相关的书籍和文献。资料选择:选择与自闭症语言障碍成因和辅助沟通技术在自闭症儿童语言发展中应用的文章,无论是否有对照组均纳入。资料提炼:将检索到的文章进一步查找全文,排除重复研究,纳入32篇为参考文献。文献中有24篇是探讨辅助沟通技术对自闭症儿童语言和沟通能力的作用的实验,涉及到92个个案,其中有21篇的结果表明辅助沟通技术对自闭症儿童的语言和沟通能力有促进作用,另外3篇的结论相反。资料综合:语言障碍是自闭症患者的核心障碍之一。辅助沟通技术是利用现代的计算机和电子技术,通过图片和符号与语音进行转换等方式,将沟通障碍者的信息传递给他人,实现与人交流的功能。辅助沟通技术的理念就是在自然情境中融入沟通的思维和方法,增加他们学习语言的动机,并提高其沟通的效率和准确度。结论:在教育和康复的临床实践中,可以利用辅助沟通技术来提高自闭症儿童的语言能力。     

跟骨定量超声骨质测量参数与骨密度及骨组织形态计量学指标的关系

目的:分析跟骨定量超声骨质测量中各参数与骨密度及形态计量学指标的相关性。方法:选择2004-01/2005-12广州市第六人民医院和中山大学三院骨科小腿以上截肢患者38例,将其跟骨定量超声测定的超声振幅衰减平均值与健康青年人骨峰值进行比较,>-2.5 SD者为骨量正常组(12例),<-2.5 SD者为骨质疏松组(26例)。分别进行跟骨定量超声、双能X线骨密度测量仪及骨形态计量学测量,应用直线相关分析法分析跟骨定量超声测定中各参数与骨密度及骨组织形态计量学各指标的相关性。结果:38例全部进入结果分析。①骨质疏松组跟骨超声振幅衰减平均值和骨硬度指数值均小于骨量正常组(P<0.01)。②骨量正常组跟骨骨密度值显著高于骨质疏松组[(352±16),(233±14)mg/cm2,P<0.01]。③骨量正常组跟骨平均骨小梁间距或弥散度低于骨质疏松组而松质骨体积高于骨质疏松组(P<0.05)。④超声振幅衰减平均值和骨硬度指数与骨密度呈直线正相关(r=0.814,0.326,P<0.01,0.05)。⑤超声传播速度与骨小梁游离末端、平均骨小梁间距呈直线负相关(r=-0.688,-0.712,P<0.01),与小梁间连点数、松质骨体积呈直线正相关(r=0.672,0.794,P<0.01);骨硬度指数与平均骨小梁间距呈直线负相关(r=-0.358,P<0.05),与松质骨体积呈直线正相关(r=0.513,P<0.01)。结论:跟骨定量超声测量中,超声振幅衰减平均值能较好地反映骨的密度,超声传播速度能较好地反映骨的质量,而骨硬度指数能较综合地反映骨强度的改变。