The purpose of this study is to investigate the penetration effects and mechanism of N-arginine chitosan (ACS). This novel transdermal enhancer with a mimetic structure of cell-penetration peptides was synthesized by introducing hydrophilic arginine groups to the amino-group on chitosan's side chain. The structure of ACS was confirmed by FT-IR, 1H NMR and element analysis. In addition, attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) was used to study the protein conformation and the water content of stratum corneum, and the result suggested that ACS can change the orderly arrangement of the molecules in the stratum corneum, making the stack structure of keratin become loose. And ACS can increase the water content of the stratum corneurn. Inverted fluorescence microscope and flow cytometry were used to examine penetration effect of ACS on Hacat cell. The result confirmed that the uptake of ACS was enhanced with increased substitution degree of arginine by 4-8 folds compared to chitosan. In vitro penetration studies on three electrical types of drugs were carried out using three model drugs of negatively charged aspirin, positively charged terazosin and neutral drug isosorbide mononitrate by the method of Franz diffusion cells. The results showed that ACS has obviously penetration of the negatively charged drug aspirin, and certain penetration of neutral drug issorbide mononitrate, but inhibition of positively charged terazosin. In vivo imaging technology research results show that the ACS can significantly enhance the fluorescence intensity of morin, which is the auto-fluorescence anionic drug. These obtained results suggested that ACS, as a promising transdermal enhancer, can change the structure of the keratinocytes and analog penetrating peptides promote absorption, but have certain selectivity for the drug.

To investigate the rat intestinal absorption of stearic acid-octaarginine (SA-R8) modified solid lipid nanoparticles containing paclitaxel (SA-R8-PTX-SLN), compared with the commercially available preparation of PTX (Taxol) and PTX-loaded solid lipid nanoparticles (PTX-SLN), the in situ intestinal absorption of SA-R8-PTX-SLN was investigated by means of single-pass rat intestinal perfusion technique. The absorptions of the preparations were investigated at different intestinal segments, different drug concentrations and in the presence of P-glycoprotein inhibitor (verapamil). The results showed that PTX could be absorbed at each intestinal segment and the three preparations all showed maximum absorptions at the duodenum. The cumulative absorptions of three preparations at each intestinal segment appeared SA-R8-PTX-SLN > PTX-SLN > Taxol (P < 0.05). SA-R8-PTX-SLN showed a liner absorption manner at the duodenum in the examined drug concentration range. The cumulative absorptions of Taxol and PTX-SLN were significantly promoted after the addition of P-glycoprotein inhibitor (verapamil) into the preparation (P < 0.05), but absorption of SA-R8-PTX-SLN existed no significantly difference compared with the preparation without verapamil (P > 0.05). SA-R8 and SLN might both effectively improve the oral absorption of PTX in the intestinal tract.

Lactoferrin (Lf) is one of the food protein belonged to the innate immune system. Apart from its main biological function of binding and transport of iron ions, lactoferrin also has many other functions and properties such as antibacterial, antiviral, antiparasitic, catalytic, anti-cancer, anti-allergic and radioprotecting. Lf is usually used as additives of food and cosmetics. The research of lactoferrin has been increasingly reported, and the application of lactoferrin as a drug carrier has drawn extensive attention over the recent year. In this paper, researches of lactoferrin as drug carriers are classified and summarized in brain targeting, liver tumor targeting, lung tumor targeting and oral delivery systems according to their different characteristics.

A novel chitosan derivant, N-octyl-N-arginine chitosan (OACS) with a mimetic structure of cell-penetrating peptides was synthesized by introducing hydrophilic arginine groups and hydrophobic octyl groups to the amino-group on chitosan's side chain. Structure of the obtained polymer was characterized by FT-IR and 1H NMR. The substitution degree of octyl and arginine groups was calculated through element analysis and spectrophotometric method, separately. The critical micelle concentration of OACS was 0.12 - 0.27 mgmL(-1) tested by fluorescence spectrometry. The solubility test showed OACS could easily dissolve in pH 1 - 12 solutions and self-assemble to form a micelle solution with light blue opalescence. The OACS micelles have a mean size of 158.4 - 224.6 nm, polydisperse index of 0.038 - 0.309 and a zeta potential of +19.16 - +30.80 mV determined by malvern zetasizer. AFM images confirmed free OACS micelle has a regular sphere form with a uniform particle size. MTT test confirmed that OACS was safe in 50 - 1 000 micromol-L(-1). The result of HepG2 cell experiment showed that the cell internalization of OACS micelles enhanced with increased substitution degree of arginine by 40 folds compared to chitosan. Thus, OACS micelles were a promising nano vehicle with permeation enhancement and drug carrier capability.

Because of the changed metabolic behaviors of cancer cells, tumor cells uptake a corresponding larger amount of glucose in physiological condition when compared with normal cells. And they were prone to metabolize glucose for generating energy in anaerobic glycolysis ways in order to grow quickly. Anaerobic glycolysis consumes more glucose than aerobic way when the same amount of energy is obtained, which also results in large demand of glucose in tumor cells. This review briefly describes therapy methods related to characteristic mentioned above, and summarizes the research progress of drugs, diagnostic reagents and carriers conjugated with glucose, glucose derivatives or other kinds of sugars for cancer targeting. Furthermore, typically relative research reports from 2012 till now were listed and analyzed.

Post competency-based medical education complies to the development and philosophy of modern medicine. This paper completely illustrates how to construct a scientific and diversified assessment evaluation system guided by post competency for medical students which combines formative assessment and summative assessment. Through the objective measurement and timely feedback of various abilities of medical students, the closed-loop feedback system of assessment and evaluation can be constructed to guide the exploration and practice of teaching process in reverse.

Objective To investigate the effects of sevoflurane pretreatment on the inflammatory response in patients undergoing cardiac valve replacement with cardiopulmonary bypass (CPB) and the mechanism of myocardial protection.Methods Twenty NYHA class Ⅱ or Ⅲ patients of both sexes,aged ＜ 60 yr,undergoing cardiac valve replacement with CPB,were randomly divided into 2 groups (n=10 each): sevoflurane group (group S) and control group (group C).The patients were premedicated with intramuscular morphine 0.1 mg/kg and scopolamine 0.3 mg.Anesthesia was induced with iv injection of midazolam 0.05-0.08 mg/kg,fentanyl 10-15 μg/kg and pipecuronium 0.08-0.10 mg/kg.The patients were tracheal intubated and mechanically ventilated.Anesthesia was maintained with intermittent iv boluses of midazolam0.03-0.06 mg/kg,fentanyl 5-10μg/kg and pipecuronium 0.04-0.08 mg/kg.Sevoflurane was inhaled before aortic clamping and the end-tidal concentration was rapidly adjusted to 1.0％ and maintained at this level for 30 min in group S.Blood samples were taken from the central vein before skin incision,immediately after aortic clamping,immediately after aortic unclamping and at 30 min after aortic unclamping,at 2,6,12 and 24 h (T1-8) after operation for determination of the concentrations of plasma tumor necrosis factor-α (TNF-α),interleukin-6 (IL) and interleukin-8 (IL-8),intercellular adhesion molecule-1 (ICAM-1),cardiac troponin I (cTnI) and activity of creatine kinase MB (CK-MB).The requirement for cardiovascular drugs was recorded after release of aortic cross clamp.Results Compared with group C,the plasma concentrations of TNF-α,IL-6 and IL-8 were significantly decreased at T3-8,the plasma concentrations of ICAM-1 and cTnl were significantly decreased at T4-8,the activity of plasma CK-MB was significantly decreased at T8,and the requirement for cardiovascular drugs was significantly reduced after release of aortic cross clamp in group S (P ＜0.05).Conclusion Sevoflurane pretreatment can inhibit the inflammatory response and provide myocardial protection to some extent in patients undergoing cardiac valve replacement with CPB.

Objective To investigate the effects of sevoflurane pretreatment on the myocardial injury in patients undergoing cardiac valve replacement with cardiopulmonary bypass (CPB).Methods Twenty NYHA class Ⅱ or Ⅲ patients,aged ＜ 60 yr,undergoing cardiac valve replacement with CPB,were randomly divided into 2 groups (n =10 each):sevoflurane group (group S) and control group (group C).The patients were premeditated with intramuscular morphine and scopolamine.Anesthesia was induced with iv injection of midazolam 0.05-0.08 mg/kg,fentanyl 10-15 μg/kg and pipecuronium 0.08-0.10 mg/kg.Anesthesia was maintained with intermittent iv boluses of midazolam,fentanyl and pipecuronium and in addition sevoflurane was inhaled before aortic clamping and the end-tidal concentration was rapidly increased to 1.0％ and maintained at the level for 5 min in group S.Blood samples were taken from the central vein before skin incision (T1),immediately after aortic clamping (T2 ),at 0 and 30 min after aortic unclamping (T3-4),and at 2,6,12 and 24 h after operation (T5-8) for determination of the concentration of serum cardiac troponin Ⅰ (cTnI) and activities of creatine kinase (CK) and creatine kinase isoenzyme-MB (CK-MB).Myocardial specimens were taken from right auricle before aortic clamping and at 10 min after aortic unclamping for electron microscopic examination.Results The concentration of serum cTnI and activities of CK and CK-MB were significantly increased at T4-8 in both groups ( P ＜ 0.05).The serum cTnI concentration at T4-8 and the activities of CK and CK-MB at T8 were significantly lower in group S than in group C ( P ＜0.05).Different degrees of mitochondrial swelling were observed after aortic unclamping in both groups,but the changes were milder in group S than in group C.Conclusion Sevoflurane pretreatment can attenuate the myocardial injury in patients undergoing cardiac valve replacement with CPB.

Objective Toexplorethevalueofmonochromaticenergyimaginggeneratedfrom RevolutionCTindetectingcoronary plaquesindifferentconcentrationsofcontrastagent.Methods Sixtesttubesnumbered3,4,5,6,8and9inthephantom wereselectedand filledupwithdifferentconcentrationsofiodinesolutions(20,10,5,2.5,0,13mgI/mL,respectively),fishbonesimulatingcalcified plaqueandstreakyporksimulatinglipid/fibrousplaque.EachtubeunderwentspectralCTscan(studygroup,70keV monochromatic energyimaging)and120kVpCTscan (controlgroup)respectivelyinRevolutionCT.Theabilityofplaquedetectionwasevaluated subjectively,andfurtheranalysis was madeontheimages withascoregreaterthanorequaltothreepoints.One-way ANOVA and Bonferroni m ethod w ere used to co m pare the C T values and C N R in different tubes in the intra-group co m parison ,w hile paired t test and M ann-W hitney U testwereusedfortheinter-groupcomparison.Results TheoverallimagequalityofNo.4,5and9testtubes inbothgroupsmettheclinicaldiagnosticlevel.Intheintra-groupcomparison,No.5testtubeshowedhigherCNRofcalcifiedplaque andNo.9testtubeshowedhigherCNRoflipidplaqueandfibrousplaquethantheothers(t=4.105-29.214,allP<0.001).Whilein theinter-groupcomparison,thestudygroupshowedsimilarCNRofcalcifiedplaqueinNo.9testtube(t=-1.576,P=0.130)tothecontrol group,andhigherCNRintheothersthanthecontrolgroup(Z=-4.074--3.815,t=-14.782--3.520,allP<0.05).Conclusion Comparedwith120kVpCTimages,monochromaticenergyimagingat70keVfrom RevolutionCTshowedbetteroverallimagequality andcoulddisplaycoronaryplaquesbetterwiththecontrastagent concentrationfrom5mgI/mLto13mgI/mL.