Simple weak-acid derivatives of paclitaxel for remote loading into liposomes and improved therapeutic effects

Liposomes are among the most successful nanocarriers; several products have been marketed, all of which were prepared by active loading methods. However, poorly water-soluble drugs without ionizable groups are usually incorporated into the lipid bi-layer of liposomes by passive loading methods, with serious drug leakage during blood circulation. Furthermore, there have been few improvements in their anti-cancer activity and safety. Herein, we designed and synthesized three weak-acid modified paclitaxel (PTX) derivatives with a one-step reaction for the remote loading of liposomal formulations. By comparison, PTX-succinic acid liposomes (PTX-SA LPs) exhibited the highest encapsulation efficiency (97.2 ± 1.8%) and drug loading (8.84 ± 0.16%); meanwhile, there was almost no change in their particle size or zeta potential within one month. Furthermore, compared with Taxol®, the PTX-SA LPs showed a 4.35-fold prolonged half-time, enhanced tumor accumulation, and an increased maximum tolerated dose (MTD) of more than 30 mg kg⁻¹. As a result, the PTX-SA LPs displayed significantly improved in vivo anti-cancer efficacy in comparison with Taxol®. Therefore, weak-acid modification is proved to be a simple and effective method to achieve remote loading and high encapsulation efficiency of poorly soluble drugs, showing great potential for clinical application.

A remote loading liposomal formulation of weak-acid paclitaxel derivative with high encapsulation efficiency and high drug loading, improved therapeutic efficiency and negligible toxicity.     

Highly stable folic acid functionalized copper-nanocluster/silica nanoparticles for selective targeting of cancer cells

In this paper, we present a novel strategy to construct folic acid functionalized conjugated Cu nanoclusters (CuNCs) and silica (SiO₂) nanocomposites for targeted detection of cancer cells. First of all, BSA capped CuNCs were encapsulated into a SiO₂ matrix. The resulting CuNCs@SiO₂ nanoparticles showed bright red fluorescence with an enhanced photoluminescence quantum yield compared with free CuNCs, as well as improved stability in a complex biological environment owning to the protection of the SiO₂ matrix. Upon attachment of folic acid via the poly-l-lysine conjugates (PLL-FA) on the surface of CuNCs@SiO₂ driven by electrostatic interaction, the as-prepared CuNCs@SiO₂/PLL-FA nanocomposites are capable of selectively recognizing folate receptor (FR) over-expressed cancer cells rather than FR-negative cells. The cell viability assay proved the low biotoxicity of CuNCs@SiO₂/PLL-FA nanocomposites toward living cells and the in vitro cellular imaging assay results demonstrated their selective endocytosis of FR-positive cells (KB cells), bringing about red fluorescence labeling within the cells. Intriguingly, our strategy provides a novel route to synthesize functional CuNCs@SiO₂/PLL-FA nanocomposites equipped with superior fluorescence properties, high stability against external stimuli and good biocompatibility, and have great application potential in bioimaging imaging and targeted cell detection.

Folic acid functionalized CuNCs@SiO₂ nanocomposites with superior fluorescence properties, high stability and good biocompatibility for targeted cell imaging.     

Enhanced light emission of quantum dot films by scattering of poly(zinc methacrylate) coating CdZnSeS/ZnS quantum dots and high refractive index BaTiO3 nanoparticles

Quantum dots (QDs) have received considerable attention in information displays owing to their high quantum yield, high colour purity and low-cost fabrication. However, light emission for ultra-thin QD films with low mass percentage of QDs still need to be improved because the blue light can directly transmit the films, leading to insufficient energy to excite the QDs. In this study, we report QD films based on a poly(zinc methacrylate) coating with alloyed green-emitting CdZnSeS/ZnS quantum dots (QDs@PZnMA) together with high refractive-index BaTiO₃ nanoparticles to enhance the scattering coefficient of the QD films. Results demonstrate a 7.5-fold increase in the absorption coefficient, 11.3-fold increase in the scattering coefficient, 8.5-fold increase in the optical density (OD) and 8.6-fold increase in the green-light emission of QD films, compared with films that have the same mass percentage of pristine QDs. This approach provides a promising strategy for developing QD optical films with high scattering and enhanced light emission for flexible displays.

We report QD films based on a poly(zinc methacrylate) coating with alloyed green-emitting CdZnSeS/ZnS quantum dots (QDs@PZnMA) together with high refractive-index BaTiO₃ nanoparticles to enhance the scattering coefficient of the QD films.     

基于文献计量学的近10年我国男护士群体的研究现状及热点分析

目的通过文献计量分析,了解2009—2019年我国男护士群体的研究热点及发展趋势,为相关研究提供参考。方法通过万方、CNKI、维普及中国生物医学文献等数据库检索2009—2019年我国男护士相关文献,对纳入文献进行内容分析并使用bicomb 2.0软件和gCLUTO 1.0软件对关键词进行词频分析和双向聚类分析。结果共纳入931篇期刊文献,获得高频关键词25个,通过聚类分析获得3个研究热点,分别为男护士的工作优势与管理、男护士的心理健康以及男护生的护理教育。结论男护士群体的受关注程度日益提高,核心期刊论坛已初具雏形,但整体研究质量不佳,未来需强化科研设计及研究实施的科学性和严谨性,从而提高文献对临床实践的指导价值。     

基于CiteSpace的血液透析动静脉内瘘研究领域的热点和前沿分析

目的:调查动静脉内瘘在血液透析应用中的研究现状,明确其研究热点和研究前沿,为动静脉内瘘科研工作提供思路以及辅助临床血液透析安全有效地进行.方法:本研究纳入2000年—2019年Web of Science数据库核心合集中检索到的有关动静脉内瘘相关文献作为数据来源,运用CiteSpaceⅤ软件绘制知识图谱,对知识主体、研究热点和研究前沿等方面进行可视化分析.结果:2000年1月1日—2019年5月9日血液透析动静脉内瘘相关研究文献发文量呈现逐年递增的趋势;发文量排名较前的国家有美国、加拿大、意大利等;发文量排名较前的研究机构有阿拉巴马大学伯明翰分校、阿拉巴马大学系统、多伦多大学等;发文量排名较前的期刊有Seminars in Dialysis、American Journal of Kidney Diseases、Nephrology Dialysis Transplantation等.通过关键词词频分析得出相关热点为"动静脉内瘘在维持性血液透析中的应用""动静脉内瘘的并发症及处理""动静脉内瘘病人相关的心理体验".得出血液透析动静脉内瘘研究领域的前沿在早期动静脉内瘘失功、超声技术在动静脉内瘘病人中的应用、人造血管、介入治疗等方面.结论:通过文献计量学的分析,明确了动静脉内瘘在血液透析领域的研究热点和研究前沿,为动静脉内瘘科研工作提供基础.     

BRAFV600E突变对甲状腺乳头状癌HMGB1及MMP-9表达的影响

目的探究BRAF^V600E突变对甲状腺乳头状癌(PTC)高迁移率族蛋白1(HMGB1)及基质金属蛋白酶-9(MMP-9)表达的影响。方法选取2018年1月至2019年11月在本院行甲状腺全切除术或次全切除术的116例PTC患者及匹配癌组织标本作为PTC组,另择同时期体检正常的30例健康人作为对照组。检测PTC患者BRAFV600E基因类型,免疫组化法及Western blot法检测PTC患者甲状腺癌组织中HMGB1、MMP-9表达情况,酶联免疫吸附法检测受试者血清HMGB1、MMP-9水平,并收集PTC患者临床资料。结果 116例PCT患者检出59例BRAF^V600E突变型、57例为BRAFV600E野生型,PTC患者BRAF^V600E突变型为50.86%(59/116)。免疫组化法分析结果显示BRAFV600E突变型HMGB1、MMP-9阳性表达率均显著高于BRAFV600E野生型,差异有统计学意义(P<0.05);Western blot法检测结果显示BRAFV600E突变型HMGB1表达量、MMP-9表达量显著高于BRAF^V600E野生型,差异有统计学意义(P<0.05)。PTC组BRAF^V600E突变型及BRAF^V600E野生型血清HMGB1、MMP-9水平均显著高于对照组,差异有统计学意义(P<0.05),PTC患者BRAFV600E突变型与BRAF^V600E野生型在血清HMGB1、MMP-9水平上比较,差异无统计学意义(P>0.05)。BRAF^V600E突变型TNM分期Ⅲ~Ⅳ期、包膜浸润、多发病灶、淋巴结转移占比显著高于BRAF^V600E野生型,差异有统计学意义(P<0.05)。二元Logistic结果显示,合并包膜浸润、多发病灶、组织HMGB1阳性、组织MMP-9阳性均是BRAF^V600E突变型的影响因素(P<0.05)。结论 PTC患者BRAF^V600E突变型组织HMGB1、MMP-9阳性表达率显著高于BRAF^V600E野生型,且组织HMGB1阳性、MMP-9阳性是BRAF^V600E突变型的影响因素。     

互联网+在出院产妇延续护理服务中的应用效果研究

目的探讨基于互联网+的随访管理模式在出院产妇产褥期延续护理服务中的应用效果。方法采用随机抽样的方法,选取在本院分娩的产妇300例作为研究对象,按出院日期分为延续护理组(观察组)和常规护理组(对照组),各150例。对照组采用出院指导、门诊复诊、电话随访的方法,观察组在常规产后随访的基础上,运用互联网手段手机APP、微信、QQ等进行随访,比较两组随访方法所取得的效果。结果观察组产妇母婴保健知识知晓率(80.67%)和婴儿护理知识的知晓率(84.67%)明显高于对照组(61.33%)和(58.67%)(P<0.05);观察组爱丁堡产后抑郁量表(EPDS)评定得分低于对照组,两组比较存在统计学差异(P<0.05);观察组产妇对护理服务的总体满意率(98.67%)明显高于对照组(90.00%)(P<0.05)。结论利用互联网信息平台为产褥期妇女提供专业、个性化、方便、高效的指导与帮助,可有效提高产妇产褥期保健知识和新生儿保健知识,有助于建立和谐护患关系,提高产妇满意度,值得临床应用。     

Comparison of Common Methodologies for the Determination of Knee Flexor Muscle Strength

BackgroundKnee flexion strength may hold important clinical implications for the determination of injury risk and readiness to return to sport following injury and orthopedic surgery. A wide array of testing methodologies and positioning options are available that require validation prior to clinical integration. The purpose of this study was to 1) investigate the validity and test-retest reliability of isometric knee flexion strength measured by a fixed handheld dynamometer (HHD) apparatus compared to a Biodex Dynamometer (BD), 2) determine the impact of body position (seated versus supine) and foot position (plantar- vs dorsiflexed) on knee flexion peak torque and 3) establish the validity and test-retest reliability of the NordBord Hamstring Dynamometer.Study DesignValidity and reliability study, test-retest design.MethodsForty-four healthy participants (aged 27 ± 4.8 years) were assessed by two raters over two testing sessions separated by three to seven days. Maximal isometric knee flexion in the seated and supine position at 90^o knee flexion was measured with both a BD and an externally fixed HHD with the foot held in maximal dorsiflexion or in plantar flexion. The validity and test-retest reliability of eccentric knee flexor strength on the NordBord hamstring dynamometer was assessed and compared with isometric strength on the BD.ResultsLevel of agreement between HHD and BD torque demonstrated low bias (bias -0.33 Nm, SD of bias 13.5 Nm; 95% LOA 26.13 Nm, -26.79 Nm). Interrater reliability of the HHD was high, varying slightly with body position (ICC range 0.9-0.97, n=44). Isometric knee flexion torque was higher in the seated versus supine position and with the foot dorsiflexed versus plantarflexed. Eccentric knee flexion torque had a high degree of correlation with isometric knee flexion torque as measured via the BD (r=0.61-0.86). The NordBord had high test-retest reliability (0.993 (95%CI 0.983-0.997, n=19) for eccentric knee flexor strength, with an MDC₉₅ of 26.88 N and 28.76 N for the left and right limbs respectively.ConclusionCommon measures of maximal isometric knee flexion display high levels of correlation and test-retest reliability. However, values obtained by an externally fixed HHD are not interchangeable with values obtained via the BD. Foot and body position should be considered and controlled during testing.Level of Evidence2b     

中西医结合护理专科护士培训后工作体验的质性研究

目的 了解中西医结合护理专科护士培训后工作真实体验,以期为完善中西医结合护理专科护士临床培训及管理提供依据.方法 采用现象学研究方法,对13名中西医结合护理专科护士进行半结构式访谈,并用Colaizzi分析7个步骤对资料进行分析.结果 归纳出3个主题:职业认同感,职业获益感,职业发展困惑.结论 中西医结合护理专科护士培训后工作中存在多种体验,需要了解心理状况,给予针对性干预.     

托吡酯与卡马西平治疗对脑梗死后继发癫痫患者神经功能缺损、日常活动能力及认知功能的影响

目的分析托吡酯与卡马西平治疗对脑梗死后继发癫痫患者神经功能缺损、日常活动能力和认知功能的影响,为临床治疗提供思路。方法选取2017年3月至2019年8月我院收入的脑梗死后继发癫痫138例患者。按随机数字表法分为A组(治疗上加以卡马西平)和B组(治疗上加以托吡酯)各69例。治疗6个月后比较两组临床效果,治疗前后神经功能缺损、日常活动能力和认知功能的评分及不良反应发生情况。结果治疗后B组疗效高于A组(P<0.05);B组神经功能缺损较治疗前明显下降,且低于A组,不同时间评估分神经功能缺损情况差异有统计学意义(P<0.001);两组日常活动能力和认知功能评分均较治疗前升高,且B组评分高于A组(P<0.05);两组不良反应发生率比较差异无统计学意义(P>0.05)。结论托吡酯的临床疗效优于卡马西平,对脑梗死后继发癫痫患者的预后恢复疗效更好,且不良反应程度轻微,值得临床推广。