Calcium Enabled Remote Loading of a Weak Acid Into pH-sensitive Liposomes and Augmented Cytosolic Delivery to Cancer Cells via the Proton Sponge Effect

Pharmaceutical Research - While delivery of chemotherapeutics to cancer cells by nanomedicines can improve therapeutic outcomes, many fail due to the low drug loading (DL), poor cellular uptake and...     

梗阻性肾功能衰竭的急诊处理

目的：总结急诊处理石结石引的梗了生肾功能衰竭的经验与教训,方法：对１９８８年１月－２０００年５月收治的８１例梗阻性肾功能衰竭患者的急诊处理方法进行回顾性分析,其中行急诊开放手术１４例,输尿管逆行插管引流,经皮肾穿刺造口３１例,引流失败的８例,１例改行ＵＲＳ,７例改行经皮肾穿刺造口,结果：死亡３例,１例为开放手术者,２例为穿刺造口者,引流成功２８例,无一例出现严惩并发症,穿刺造口者有３例行肾切除术,手术手病情改善,血清肌酐下降,结论：对此类患者应特别注意出血倾向对外科手术的严重影响,在患者出血倾血向未得到纠正以前切勿轻易进行复杂的外科处理,推荐输尿管逆行插管引流个为梗阻性肾功能衰竭急诊处理的首选方法。     

Dual or multiple drug loaded nanoparticles to target breast cancer stem cells

Breast cancer stem(-like) cells (BCSCs) have been found to be responsible for therapeutic resistance and disease relapse. BCSCs are difficult to eradicate due to their high resistance to conventional treatments and high plasticity. Functionalised nanoparticles have been investigated as smart vehicles to transport across various barriers and increase the interaction of therapeutic agents with cancer cells, as well as BCSCs. In this review, we discuss the different characteristics of BCSCs, and challenges to tackle BCSCs at cellular and molecular levels. The mechanisms of action and physicochemical properties of the current BCSC targeting agents are also covered. We will focus on the rational design and recent advances of “Nano + Nano” or single tumour targeting nanoparticle systems loaded with dual or multiple agents to kill all cancer cells including BCSCs. These cocktail therapies include the combination of a chemotherapy agent with a BCSC-specific inhibitor, a phytochemical agent or RNA based therapy. Given the heterogeneity of breast tumour tissue, targeting both BCSCs and bulk breast cancer cells simultaneously with multiple agents holds great promise in eliminating breast cancer. The future research needs to focus on overcoming various barriers in the ‘clinical translation’ of BCSC-targeting nanomedicines to cure breast cancer, which requires a significant multidisciplinary effort.

Breast cancer stem(-like) cells (BCSCs) have been found to be responsible for therapeutic resistance and disease relapse.     

鹿角形肾结石联合治疗中以肾中盏为目标肾盏的临床研究

目的 探讨鹿角形肾结石气压弹道联合超声碎石治疗中以肾中盏为目标肾盏的临床效果及安全性.方法 采用气压弹道联合超声碎石的方式,以肾中盏为目标肾盏行经皮肾镜碎石术（PCNL）治疗鹿角形肾结石患者73例92侧,其中不完全性鹿角形肾结石57侧,完全性鹿角形肾结石35侧.观察结石的排除率及并发症.结果 72例行一期单通道碎石（中盏）,其中3例行一期双通道碎石（中盏及下盏2例,中盏及上盏1例）;1例（1侧）残留肾盏结石未进一步处理,自动出院.16侧行二期碎石,均为单通道,其中2侧先行体外冲击波碎石术（ESWL）再行PCNL碎石;76侧排尽结石,其中完全性鹿角形肾结石27侧,不完全性鹿角形肾结石49侧,结石清除率82.6％ （76/92）.血红蛋白下降1 ～4g/L,术中输血11例,术后输血3例;术后肾盂内感染1例,合并肾周感染、单侧分肾功能受损1例.结论 以肾中盏为目标肾盏行PCNL治疗鹿角形肾结石是非常有效和安全的,气压弹道联合超声碎石对鹿角形结石的清除率较高,治疗时间短,并发症少.     

Investigation on the release of fluorescent markers from w/o/w emulsions by fluorescence-activated cell sorter.

The mechanism of release of two fluorescent markers, fluorescein isothiocyanate-bovine serum albumin (FITC-BSA) and fluorescein, from water-in-oil-in-water (w/o/w) emulsions was investigated using a rapid and sensitive method based on fluorescence-activated cell sorting (FACS). The release of FITC-BSA from a w/o/w emulsion was controlled by diffusion rather than by simple breakdown of the multiple droplets or by formation of reverse micelles in the oil phase. In contrast, the release of fluorescein from a double emulsion was controlled by formation of reverse micelles rather than by diffusion or simple breakdown of multiple droplets. A significant difference in the yield and fraction of FITC-BSA and fluorescein released from double emulsions was observed due to their different molecular structure and properties. The yield of FITC-BSA incorporation in a double emulsion increased with increasing FITC-BSA concentration in the internal water phase, while the yield of fluorescein decreased with increasing concentration. The fraction of FITC-BSA released from a w/o/w emulsion after 24 h decreased with an increasing concentration of FITC-BSA in the internal phase. The w/o/w emulsion with internalized FITC-BSA was more stable than that with fluorescein, indicating its further application for sorting or enriching size-controlled double droplets that contained genes and water-soluble drugs.     

Pharmacokinetics and metabolism of Chf197, a ligustrazine derivative,in rats

Ligustrazine is the most abundant and bioactive ingredient in Rhizoma Chuanxiong, a Chinese medicinal herb commonly used for the treatment of cardiovascular diseases. Chf197 is one of the structurally modified ligustrazine derivatives in a purpose of overcoming the rapid metabolism and short half‐life of original. The plasma and urine pharmacokinetics of Chf197 in rats were studied after intravenous or intraperitoneal injection of Chf197 with the validated RP‐HPLC method. The pharmacokinetic parameters of Chf197 injected intravenously 20 mg/kg were as follows: C_max, 1.44 ± 0.4 mg/L; T_max, 0.08 h; t_1/2, 3.03 ± 1.67 h; AUC, 3.85 ± 3.88 h/L; V_d, 31.66 ± 11.79L/kg; and CL, 9.29 ± 4.92 l/h/kg. Dose‐dependent pharmacokinetics was observed, and a significantly higher dose‐normalized AUC after intravenous administration was obtained than that after intraperitoneal administration. A possible metabolite was detected at about 3.1 min, and full‐scan mass spectrum was adopted to predict its possible structure.