ABSTRACT
Metastasis accounts for 90% of breast cancer deaths, where the lethality could be attributed to the poor drug accumulation at the metastatic loci. The tolerance to chemotherapy induced by breast cancer stem cells (BCSCs) and their particular redox microenvironment further aggravate the therapeutic dilemma. To be specific, therapy-resistant BCSCs can differentiate into heterogeneous tumor cells constantly, and simultaneously dynamic maintenance of redox homeostasis promote tumor cells to retro-differentiate into stem-like state in response to cytotoxic chemotherapy. Herein, we develop a specifically-designed biomimic platform employing neutrophil membrane as shell to inherit a neutrophil-like tumor-targeting capability, and anchored chemotherapeutic and BCSCs-differentiating reagents with nitroimidazole (NI) to yield two hypoxia-responsive prodrugs, which could be encapsulated into a polymeric nitroimidazole core. The platform can actively target the lung metastasis sites of triple negative breast cancer (TNBC), and release the escorted drugs upon being triggered by the hypoxia microenvironment. During the responsiveness, the differentiating agent could promote transferring BCSCs into non-BCSCs, and simultaneously the nitroimidazole moieties conjugated on the polymer and prodrugs could modulate the tumor microenvironment by depleting nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) and amplifying intracellular oxidative stress to prevent tumor cells retro-differentiation into BCSCs. In combination, the BCSCs differentiation and tumor microenvironment modulation synergistically could enhance the chemotherapeutic cytotoxicity, and remarkably suppress tumor growth and lung metastasis. Hopefully, this work can provide a new insight in to comprehensively treat TNBC and lung metastasis using a versatile platform.
ABSTRACT
OBJECTIVE:To provide reference for clinical individual medication of voriconatole. METHODS:The distribution of MIC of voriconazole to Aspergillus fumigatus and Candida albicans were summarized as well as the pharmacokinetic parameters of voriconazole in different populations. Using probability of target attainment(PTA)and cumulative fraction of response(CFR)as indexes,crystal ball software 11.1.2.4 was used for Monte Carlo simulation of different dosage regimens of same population and same dosage regimen of different populations. RESULTS:For children with impaired immunity,when the drug doses of were 4,6 mg/kg and MIC was lower than 0.125 mg/L,PTA was higher than 90%;when the drug doses was increased to 8 mg/kg and MIC was lower than 0.125 mg/L,PTA was higher than 90%. For different populations receiving same dosage regimens(4 mg/kg),MIC of teenagers with impaired immunity was lower than 0.25 mg/L and those of healthy adults,patients underwent hematopoietic stem cell transplantation and adults with impaired immunity were all lower than 0.5 mg/L,PTA was higher than 90%. CFR to A. fumigatus were 42.53%,58.41%,77.74%,70.16%,89.40%,93.72%,95.42% and CFR to C. albicans were 96.68%,97.13%,97.94%, 97.54%,98.07%,98.28%,98.35%among children with impaired immunity receiving different drug doses(4,6,8 mg/kg)and dif-ferent populations receiving drug dose of 4 mg/kg(teenagers with impaired immunity,healthy adults,patients underwent hemato-poietic stem cell transplantation,adults with impaired immunity). CONCLUSIONS:Various dosage regimens of different popula-tions included in this study could effectively control C. albicans infection. It is necessary to increase the drug dose of children and teenagers with impaired immunity in order to meet the needs of A. fumigatus infection treatment.
ABSTRACT
At present,the study of intestinal absorption of oral drugs mainly includes in vitro,in vivo and in situ methods.In view of the advantages of in situ intestinal perfusion such as simple operation,mature technology,controllable,ensure the neuroendocrine regulation and blood supply,and so on,which could better reflect the true situation of drug absorption.In this study,the research methods and characteristics of intestinal absorption of oral drugs were systematically introduced.The recirculating perfusion method and single-pass perfusion method were compared,and several volume correction methods were also introduced.In order to ensure the operability and accuracy of experimental results,proper experiment method of intestinal absorption will be adopt according to the factors such as drug characters,experiment requirements,experimental conditions,and so on.The article provides a scientific basis for the development of pharmaceutical dosage and clinical rational drug use.
ABSTRACT
Objective To assess the effectiveness of Chinese materia medica (CMM) as adjuvant therapy of antibacterial for pediatric mesenteric lymphadenitis.Methods Retrieved RCT research of CMM as adjuvant therapy of antibacterial for pediatric mesenteric lymphadenitis from CNKI,Wanfang,VIP,PubMed,and Medline database from 1980 to 2016.Literatures were selected according to the inclusion and exclusion crteria,Jadad scores method was used to evaluate the literatures and meta-analysis was performed by RevMan 5.3.Results A total of 34 randomized controlled trials were included.Meta-analysis showed that the trial group was superior to the control group in terms of efficiency,cure rate,remission time of main symptoms,mesenteric lymph node recovery,and recurrence rate,there was statistical difference.Conclusions CMM as adjuvant therapy of antibacterial for pediatric mesenteric lymphadenitis is more effective than the use of antibacterial alone.
ABSTRACT
This article describes the design and development of an ultrasonic power meter which is consist of an electronic balance, a practice target, an acoustic enclosures and a blocking. The electronic balance mounted on the blocking is linked with the practice target by connecting rod. By adjusting the blocking makes the practice target suspended above ultrasound probe, and then the ultrasonic power can be measured. After initial tests, the ultrasonic power meter performanced with good stability and high precision.
Subject(s)
Equipment Design , UltrasonicsABSTRACT
Objective To study the antidepressant effect of total timosaponin(TT)and its mechanism.Methods The antidepressant effect of TT was examined by mice forced swimming test(FST),learned helplessness(LH)experiment,chronic mild stress(CMS)model,yohimbine induced lethality test and 5-HTP induced head-twitches test.Results TT(25 or 50 mg?kg-1,ig,qd?14 d)markedly shortened the immobility time in the FST,but didn't affect the autonomic activity.TT(12.5,25 or 50 mg?kg-1,ig,qd?14 d)significantly decreased the number of escape deficits in the LH mice.TT(25 or 50 mg?kg-1,ig,qd?21 d)markedly enhanced the locomotor activity and increased consumption of sucrose solution in CMS mice.TT(50 mg?kg-1,ig,qd?14 d)enhanced the mortality of mice after administration of yohimbine for 4 h,and distinctly increased the head-twitch number in the 5-HTP induced head-twitches test.Conclusion TT has antidepressant effects in various depression mouse models.Its mechanism may be related to the reinforcement of NE and 5-HT nerves system.