成人急性髓系白血病治疗现状及新药研究进展

急性髓系白血病（Acute myeloid leukemia, AML）是一类高度异质性疾病,过去常规诱导化疗和各类支持治疗为主,但随着二代测序等技术应用以来,AML药物迅速发展。本文从细胞毒药物、小分子靶向药物以及免疫靶向药物等方面,系统概述AML的致病机制,以及临床研究中较为前沿的各类新型药物（如FLT3抑制剂Midostaurin、IDH抑制剂AG-221和CPX-351等）的研究进展,旨在为AML的新药研发提供参考。     

pH敏感型纳米递药系统在肿瘤靶向治疗中的作用

目的 综述目前pH敏感纳米递药系统用于肿瘤靶向治疗中的国内外研究进展。方法 在Pubmed和Google上检索近年国内外资料,阐明pH敏感纳米递药系统靶向肿瘤治疗的作用机制,对超顺磁性纳米粒、胶束、树状大分子等相关研究成果进行总结和评价。结果 传统肿瘤化疗药物普遍存在疗效低、副作用大等问题,而近年来研发的pH响应的纳米载体可通过EPR效应积聚于肿瘤组织,并在弱酸性的肿瘤细胞外液或经内吞作用后在细胞质或溶酶体中释放药物。该pH敏感型载体能促进药物的靶向递送,在减少系统性副作用的同时提高肿瘤化疗疗效。结论 pH敏感纳米递药系统在肿瘤靶向治疗中具有广阔的应用前景,开发具有靶向性、高效性、安全性的递药系统是目前该领域研究主要方向之一。     

丁苯酞联合脑循环治疗仪对急性脑梗死患者神经功能及脑循环状态的影响

摘 要 目的：探讨丁苯酞注射液联合脑循环治疗仪对急性脑梗死患者神经功能及脑循环状态的影响。方法: 120例急性脑梗死患者随机分为3组,每组40例。C组给予常规治疗;A组给予常规治疗＋丁苯酞注射液治疗;B组给予常规治疗＋丁苯酞注射液＋小脑电刺激治疗。3组均连续治疗21d。评估3组的临床疗效,比较3组治疗前后的NIHSS评分、改良Rankin量表（mRS）评分、双侧大脑中动脉峰值流速（Vp）、平均血流速度（Vm）、双侧差值(Dvp、Dvm)等脑血流动力学参数及血管搏动指数、脑循环储备功能的变化。结果: 治疗后,B组总有效率为92.5%,明显高于C组的72.5%（P＜0.05）。3组治疗后NIHSS、mRS评分均较治疗前明显下降(P＜0.05),且B组两项评分明显低于C组(P＜0.05)。3组治疗后Vp、Vm 均较前明显升高,DVp、DVm及血管搏动指数较前明显下降,脑循环储备功能明显改善(P＜0.05);A、B组各项参数均优于C组（P＜0.05）,且B组优于A组（P＜0.05）。结论: 丁苯酞注射液联合脑循环功能仪治疗可显著改善急性脑梗死患者的神经功能,纠正脑循环状态异常。     

糖尿病周围神经病变综合康复治疗60例疗效观察

目的 探讨综合康复治疗对于糖尿病周围神经病变的临床疗效.方法 研究纳入120例糖尿病周围神经病变的患者,按照完全随机分组法分为常规治疗组和综合康复治疗组,其中常规治疗组(60例)患者采用常规方法治疗,综合康复治疗组(60例)患者在常规方法之外接受红外线照射和/或高压氧治疗.对比常规治疗组和综合康复治疗组的治疗效果.结果 治疗1个月后,综合康复治疗组患者的显著有效率(78.56% vs 50.00%)和总有效率(96.67% vs 86.67%)均高于常规治疗组,差异有统计学意义(显著有效率:χ2=11.868,P=0.001;总有效率:χ2=3.927,P=0.048).治疗后综合康复组患者腓总神经[(43.5 ±3.1)vs(37.3 ±2.9)m· s-1]和胫神经传导速度[(44.5 ±3.2)vs(38.6 ±2.5)m· s-1]均显著高于常规治疗组患者(腓总神经:t=12.815,P<0.001;胫神经:t=11.102,P<0.001).结论 综合康复治疗能够明显改善糖尿病周围神经病变患者症状,提高患者周围神经功能.     

合理情绪疗法对经皮冠状动脉介入治疗的冠心病患者心理弹性水平的影响

目的 探讨合理情绪疗法对经皮冠状动脉介入治疗的冠心病患者心理弹性水平的影响.方法 对2015年11月至2016年8月安庆市立医院44例经皮冠状动脉介入治疗冠心病患者,按随机数字表法随机分为干预组和对照组,每组22例.两组均进行常规健康教育,干预组在此基础上进行每周2次、共6次的合理情绪疗法联合放松训练.干预前后两组均采用中文版心理弹性量表(CD-RISC)、综合医院焦虑抑郁(HAD)量表对患者进行测评,评估干预效果.结果 干预前,两组CD-RISC、焦虑、抑郁得分比较差异均无统计学意义(依次t=0.003,P=0.997;t=-0.802,P=0.431;t=0.514,P=0.613).干预3周后,干预组CD-RISC得分为(66.80±9.72)分,高于干预前,差异有统计学意义(t=-4.61,P=0.001),焦虑得分为(9.20±2.25)分,抑郁得分为(10.00±3.27)分,得分均低于干预前,差异有统计学意义(依次t=4.58,P=0.001;t=5.02,P=0.001).对照组干预前后CD-RISC差值为(0.77±1.54)分,干预组干预前后CD-RISC差值为(2.40±1.65)分,差异有统计学意义(t=2.45,P=0.023);对照组干预前后焦虑得分差值为(-0.46±0.78)分,干预组干预前后焦虑得分差值为(-1.40±0.97)分,差异有统计学意义(t=-2.59,P=0.017);对照组干预前后抑郁得分差值为(-0.38±0.65)分,干预组干预前后抑郁得分差值为(-1.90±1.20)分,差异有统计学意义(t=-3.89,P=0.001).结论 合理情绪疗法能有效增强PCI患者心理弹性水平,减轻焦虑和抑郁症状,提高患者生活质量.     

植入式输液港与外周静脉置入中心静脉导管在化疗患者中长期随访效果观察

目的 观察比较植入式输液港(IVAP)与外周静脉置入中心静脉导管(PICC)应用于化疗患者的中长期效果,为血管通路的科学选择提供依据。 方法 选择2014年4月至2015年4月安徽医科大学第一附属医院272例化疗患者为研究对象,根据中心静脉置管方式不同分为IVAP组115例,PICC组157例,置管方式由患者意愿决定。分别对IVAP组和PICC组患者进行跟踪随访,直到导管取出或此项研究结束(2017年4月30日)止,比较两组患者一次性操作成功率、导管相关性并发症、舒适度。 结果 在一次性操作成功率、导管相关症状性血栓、导管相关性感染、堵管、疼痛方面,两组比较差异无统计学意义(P>0.05);IVAP组湿疹、异位、总体并发症发生率(0.87%,0.00%,10.43%)均低于PICC组(12.10%,8.28%,33.76%),差异有统计学意义(P<0.05)。IVAP组舒适度得分(6.97±0.97)分高于PICC组(5.98±0.58)分,差异有统计学意义(P<0.05)。 结论 IVAP与PICC均为安全的中心静脉置管方式。在减少并发症和提高患者舒适度方面IVAP优于PICC,临床实际应用时要全面综合评估患者,合理制定置管方案,科学选择血管通路。     

Selective induction of apoptosis in MCF7 cancer-cell by targeted liposomes functionalised with mannose-6-phosphate

Liposomes are versatile platforms to carry anticancer drugs in targeted drug delivery; they can be surface modified by different strategies and, when coupled with targeting ligands, are able to increase cellular internalisation and organelle-specific drug delivery. An interesting strategy of antitumoral therapy could involve the use of lysosomotropic ligand-targeted liposomes loaded with molecules, which can induce lysosomal membrane permeabilization (LMP), leakage of cathepsins into the cytoplasm and subsequent apoptosis. We have previously demonstrated the ability of liposomes functionalised with a mannose-6-phosphate to reach lysosomes; in this research we compare the behaviour of M6P-modified and non-functionalised liposomes in MCF7 tumour cell and in HDF normal cells. With this aim, we first demonstrated by Western blotting the overexpression of mannose-6-phosphate/insulin-like growth factor (M6P/IGF-II) receptor in MCF7. Then, we prepared calcein-loaded liposomes and we revealed the increased uptake of M6P-functionalised liposomes in MCF7 cells respect to HDF cells by flow cytometry analysis. Finally, we loaded functionalised and not functionalised liposomes with N-hexanoyl-d-erythro-sphingosine (C6Cer), able to initiate LMP-induced apoptosis; after having studied the stability of both vesicles in the presence of serum by Dynamic Light Scattering and Spectrophotometric turbidity measurements, we showed that ceramide-loaded M6P-liposomes significantly increased apoptosis in MCF7 with respect to HDF cells.     

Ratiometric delivery of two therapeutic candidates with inherently dissimilar physicochemical property through pH-sensitive core–shell nanoparticles targeting the heterogeneous tumor cells of glioma

Currently, combination drug therapy is one of the most effective approaches to glioma treatment. However, due to the inherent dissimilar pharmacokinetics of individual drugs and blood brain barriers, it was difficult for the concomitant drugs to simultaneously be delivered to glioma in an optimal dose ratio manner. Herein, a cationic micellar core (Cur-M) was first prepared from d-α-tocopherol-grafted-ε-polylysine polymer to encapsulate the hydrophobic curcumin, followed by dopamine-modified-poly-γ-glutamic acid polymer further deposited on its surface as a anion shell through pH-sensitive linkage to encapsulate the hydrophilic doxorubicin (DOX) hydrochloride. By controlling the combinational Cur/DOX molar ratio at 3:1, a pH-sensitive core–shell nanoparticle (PDCP-NP) was constructed to simultaneously target the cancer stem cells (CSCs) and the differentiated tumor cells. PDCP-NP exhibited a dynamic diameter of 160.8?nm and a zeta-potential of –30.5?mV, while its core–shell structure was further confirmed by XPS and TEM. The ratiometric delivery capability of PDCP-NP was confirmed by in vitro and in vivo studies, in comparison with the cocktail Cur/DOX solution. Meanwhile, the percentage of CSCs in tumors was significantly decreased from 4.16% to 0.95% after treatment with PDCP-NP. Overall, PDCP-NP may be a promising carrier for the combination therapy with drug candidates having dissimilar physicochemical properties.     

Stabilized tetraether lipids based particles guided prophyrins photodynamic therapy

Photodynamic therapy (PDT) that involves ergonomically delivered light in the presence of archetypical photosensitizer such as Protoporphyrin IX (PpIX) is a time-honored missile strategy in cancer therapeutics. Yet, the premature release of PpIX is one of the most abundant dilemma encounters the therapeutic outcomes of PDT due to associated toxicity and redistribution to serum proteins. In this study, ultrastable tetraether lipids (TELs) based liposomes were developed. PpIX molecules were identified to reside physically in the monolayer; thereby the inherent π-π stacking that leads to aggregation of PpIX in aqueous milieu was dramatically improved. TEL_29.9?mol% and TEL_62mol% based liposomes revealed PpIX sustained release diffusion pattern from spherical particles as confirmed by converged fitting to Baker &; Lonsdale model. Stability in presence of human serum albumins, a key element for PDT accomplishment was emphasized. The epitome candidates were selected for vascular photodynamic (vPDT) in in-Ovo chick chorioallantoic membrane. Profoundly, TEL_62mol% based liposomes proved to be the most effective liposomes that demonstrated localized effect within the irradiated area without eliciting quiescent vasculatures damages. Cellular photodynamic therapy (cPDT) revealed that various radiant exposure doses of 134, 202, 403 or 672?mJ.cm^?2 could deliberately modulate the photo-responses of PpIX in TEL-liposomes.