导管相关性血流感染预防措施依从性调查及执行效果评价

目的了解成人监护中心静脉导管相关血流感染（CLABSI）的集束化预防措施依从性现状,并评价其执行效果。方法对2012年10月~2013年6月入住外科监护室（SICU）、急诊监护室（EICU）、心脏监护室（CCU）和呼吸监护室（RCU）时间〉48 h的病例进行目标性监测,填写CLABSI相关监测信息并如实填写临床对于置管患者执行5大循证预防措施的情况,包括手卫生、置管时最大无菌屏障、2.0%氯己定皮肤消毒、选取适宜置管部位和每日评估尽早拔管。比较各监护室预防措施依从性及CLABSI感染率。结果各监护室对预防措施总依从性为74.5%,CLABSI感染率为6.4‰;其中,RCU预防措施依从性最低（60.2%）,感染率最高（10.5‰）;SICU预防措施依从性最高（84.4%）,感染率最低（2.1‰）,差异有统计学意义（P〈0.05）。结论目标性监测和有效的干预可以减少CLABSI的发生率。     

肺腺癌EGFR突变患者一线化疗与靶向治疗生存分析

目的 对肺腺癌EGFR19号外显子缺失和EGFR21号外显子突变患者一线化疗和靶向治疗进行生存分析.方法 回顾性收集番禺中心医院就诊的101例肺腺癌患者资料,筛选出45例已做EGFR检测的患者,分析EGFR基因突变与临床各病理参数之间的关系.在45例EGFR基因突变患者中,筛选出19例19号外显子缺失和14例21号外显子突变患者,分别分析其一线化疗和靶向治疗生存状况.结果 19号外显子缺失患者的中位总生存期(OS)为11.2个月,较21号外显子突变者的10.3个月长,差异具有统计学意义(P<0.05);19号外显子缺失患者靶向治疗的OS为12.2个月,较一线化疗的10.1个月长,差异具有统计学意义(P<0.05);21外显子突变患者靶向治疗的OS为11.5个月,较一线化疗的8.3个月时间长,差异具有统计学意义(P<0.05).结论 在肺腺癌EGFR19号外显子缺失和EGFR21外显子突变患者中,靶向治疗总生存时间较一线化疗的总生存时间长.     

超声靶向微泡破裂介导EGFP质粒转染肝癌细胞的研究

目的探讨超声靶向微泡破裂(Ultrasound Targeted Microbubble Destruction,UTMD)介导EGFP质粒转染肝癌细胞株HepG2的有效性、安全性并优化超声辐照参数。方法体外培养HepG2细胞,在不同治疗超声的声强、占空比和辐照时间作用下,观察pEGFP-N3质粒在HepG2细胞中的转染。荧光显微镜下观察绿色荧光蛋白在HepG2细胞中的表达,流式细胞仪检测细胞的转染率,MTT法检测细胞活性。结果在超声声强为2 w/cm2、占空比为20%、照射时间为60 s时,HepG2细胞的7转染率最高,达到11.53%±2.15%,且细胞生存率大于85%。结论 UTMD是一种有效的基因转染方法,不同的超声转染参数对细胞活力和基因传输效率有较大影响,对其进行优化后可减少细胞损伤,增强基因转染。     

组织因子在肿瘤侵袭中的作用和实验性靶向治疗进展

组织因子(TF)是生理性凝血过程中最重要的启动因子.TF除了参与凝血过程外,还可与凝血凼子Ⅶ结合通过多种信号传导,在肿瘤生长、血管生成及侵袭、转移过程中发挥重要作用.近年来,针对TF的靶向治疗取得了令人瞩目的进展,显示出对肿瘤组织及转移灶的明显抑制作用.     

181例胃肠间质瘤的临床病理及预后分析

目的探讨胃肠间质瘤（GIST）的临床诊治经验,分析其病理特征和影响GIST预后的因素,方法回顾性分析1999年1月至2007年12月间经手术治疗的181例GIST患者的临床病理及随访资料,根据FJetcher推荐的生物学行为分级法进行分组,比较不同因素对生存率的影响并进行预后分析。结果本组GIST病变部位：胃107例（59．1％）,小肠51例（28．2％）,结直肠等其他部位23例（12．7％）;伴有肝转移7例。172例（95．0％）术前通过影像学检查明确病灶部位,其中胃镜53．5％（92／172）,CT 34,3％（59／172）,超声内镜或胶囊内镜17．4％（30／172）。瘤体长径0．5～30．0cm不等,平均7．0cm。CD117阳性171例（94．5％）,CD34阳性156例（86．2％）。外科手术完全切除176例,其中合并联合脏器切除26例;姑息性切除或活检术5例。全组患者1、3、5年生存率分别为95．2％、87．9％和78．5％。单因素分析显示,年龄、肿瘤大小、肿瘤原发部位、核分裂像数目、FIetcher分级和是否合并联合脏器切除对生存率有影响（P〈0．05）;多因素分析显示,Fletcher分级和肿瘤大小是影响预后的因素。术后有8例高危患者和3例复发转移患者服用伊马替尼后病情稳定。结论内镜和CT是GIST有效的诊断手段,用FIetcher分级法来判断GIST的生物学行为和预测预后是简单、有效的方法,外科手术仍是目前GIST的主要治疗方法,而结合靶向治疗将成为改善GIST预后的重要手段。     

Dual Frequency Method for Simultaneous Translation and Real-Time Imaging of Ultrasound Contrast Agents Within Large Blood Vessels

A dual frequency excitation method for simultaneous translation and selective real-time imaging of microbubbles is presented. The method can distinguish signals originating from free flowing and static microbubbles. This method is implemented on a programmable scanner with a broadband linear array. The programmable interface allows for dynamic variations in the acoustic parameters and aperture attributes, enabling application of this method to large blood vessels located at varying depths. The performance of the method was evaluated in vitro (vessel diameter 2mm) by quantifying the sensitivity of the method to various acoustic, microbubble, and fluid flow parameters. It was observed that the static microbubble response maximized at the approximate resonance frequency of the microbubble population (estimated from a coulter counter measurement), thus, signifying the need for dual frequency excitation. The static microbubble signal declined from 25 to 12 dB with increasing centerline flow velocities (2.65–15.9cm/s); indicating the applicable range of flow velocities. The maximum intensity of the static microbubbles signal scaled with variations in the microbubble concentration. The rate of increment of static microbubble signal was independent of microbubble concentration. It was deduced that the rate of increment of the static microbubble signal is primarily a function of the pulse frequency, whereas the maximum static microbubble signal intensity is dependent on three parameters: (a) the pulse frequency, (b) the flow velocity and (c) the microbubble concentration. The proposed dual frequency sequence may enable the application of radiation force for optimizing the effect of targeted imaging and modulating drug delivery in large blood vessels with high flow velocities. (E-mail: avp2b@virginia.edu)     

CD98 siRNA-loaded nanoparticles decrease hepatic steatosis in mice

Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid hepatic accumulation. Here, we investigated whether a reduction of CD98 expression mediated by CD98 siRNA-loaded nanoparticles (NPs) could attenuate liver disease markers in a mouse model of NAFLD. NPs were generated using a double emulsion/solvent evaporation technique. Mice fed a high fat diet for 8 weeks to induce fatty liver were treated with vein tail injections of CD98 siRNA-loaded NPs. In vitro, HepG2 treated with CD98 siRNA-loaded NPs showed significant downregulation of CD98 leading to a significant decrease of major pro-inflammatory cytokines and markers. In vivo, CD98 siRNA-loaded NPs strongly decreased all markers of NAFLD, including the blood levels of ALT and lipids accumulation, fibrosis evidence and pro-inflammatory cytokines. In conclusion, our results indicate that CD98 appears to function as a key actor/inducer in NAFLD, and that our NPs approach may offer a new targeted therapeutic for this disease.     

Identification of potential therapeutic target of naringenin in breast cancer stem cells inhibition by bioinformatics and in vitro studies

Cancer therapy is a strategic measure in inhibiting breast cancer stem cell (BCSC) pathways. Naringenin, a citrus flavonoid, was found to increase breast cancer cells’ sensitivity to chemotherapeutic agents. Bioinformatics study and 3D tumorsphere in vitro modeling in breast cancer (mammosphere) were used in this study, which aims to explore the potential therapeutic targets of naringenin (PTTNs) in inhibiting BCSCs. Bioinformatic analyses identified direct target proteins (DTPs), indirect target proteins (ITPs), naringenin-mediated proteins (NMPs), BCSC regulatory genes, and PTTNs. The PTTNs were further analyzed for gene ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, protein–protein interaction (PPI) networks, and hub protein selection. Mammospheres were cultured in serum-free media. The effects of naringenin were measured by MTT-based cytotoxicity, mammosphere forming potential (MFP), colony formation, scratch wound-healing assay, and flow cytometry-based cell cycle analyses and apoptosis assays. Gene expression analysis was performed using real-time quantitative polymerase chain reaction (q-RT PCR). Bioinformatics analysis revealed p53 and estrogen receptor alpha (ERα) as PTTNs, and KEGG pathway enrichment analysis revealed that TGF-ß and Wnt/ß-catenin pathways are regulated by PTTNs. Naringenin demonstrated cytotoxicity and inhibited mammosphere and colony formation, migration, and epithelial to mesenchymal transition in the mammosphere. The mRNA of tumor suppressors P53 and ERα were downregulated in the mammosphere, but were significantly upregulated upon naringenin treatment. By modulating the P53 and ERα mRNA, naringenin has the potential of inhibiting BCSCs. Further studies on the molecular mechanism and formulation of naringenin in BCSCs would be beneficial for its development as a BCSC-targeting drug.