· Age-related macular degeneration (AMD) is the leading cause of legal blindness in individuals aged over 65 in the United States and other industrialized nations. Till now, we have limited choices of treatment for this kind of disease. Treatment available can be grouped into two major categories: physical and pharmacological therapies. The former received extensive attention with little success whereas the latter attract new attention with great hope of success. The pharmacological therapies indude photodynamic therapy (PDT), steroids, vascular endothelial growth factor (VEGF) inhibitors, extracellular matrix (ECM) modifiers, gene therapy, nutrition supplements, choroidal blood flow facilitators and the like. PDT treatment is the only available effective treatment for certain forms of neovascular AMD. Anecortave acetate,as a synthetic derivative of cortisol, might stabilize vision in patients with predominantly classic subfoveal choroidal neovascularization (CNV) for up to 6mo through subtenon juxtascleral depot application. Intravitreous injection of VEGF aptamer stabilized or improved vision in 87.5% of patients with subfoveal CNV 3mo after treatment. Malfunction of choroidal blood flow is found in early stage of AMD. Elevation of intravascular pressure is the crucial hemodynamic factor in age-related macular degeneration, resulting in a decrease of the blood flow of choriocapillaries. Chain reactions are triggered which lead to retinal pigment epithelium (RPE) degeneration,Bruch's membrane breakdown, CNV formation, AMD and blindness in the end. Therefore, specific drugs that can increase the choroidal blood flow could be very useful to prevent the AMD from developing and worsening. Although most of them are still in the experimental stage,it is hopeful to find a way to treat AMD at the early stage and to prevent the disease to be triggered and developed.

·AIM: Impairment of choroidal perfusion was found in AMD patients. We postulated that vasoactive agents,which can reduce choroidal blood flow resistance, might prevent the development of choroidal neovascularization (CNV). D-Timolol and L-Timolol are hypotensive agents used in cardiovascular and glaucoma therapy. Their effects on laser-induced experimental CNV rat model and human umbilical vein endothelial cells (HUVEC) were thus evaluated.·METHODS: Male Brown Norway rats were anesthetized to receive Nd:YAG laser to break the Bruch's membrane. D-Timolol and L-Timolol were given once daily through intraperitoneal injection after laser treatment for 4wk. Fluorescein angiography was performed on 2wk and 4wk. HUVEC were tested by proliferation assay and adhesion assay with D-Timolol and L-Timolol at different concentrations.· RESULTS: D-Timolol reduced the fluorescein leakage to 83% of the control group in laser-induced rat's CNV model at a dosage of 15mg/(kg·d). L-Timolol had no effect on CNV formation even at a higher dosage of 20mg/(kg·d). D-Timolol inhibited the endothelial cells proliferation significantly by 300mg/L. L-Timolol also significantly inhibited the cell proliferation at 1 000mg/L. But at a lower dose such as 300mg/L, no significant inhibitory effect was found. Both drugs showed no effect on cell adhesion function in cell culture experiments.· CONCLUSION: D-Timolol was found to prevent CNV development in laser-induced model in vivo and inhibit vascular endothelial cells proliferation in vitro. L-Timolol had no effect on cell proliferation at the same dose, and neither on rat CNV model. The results indicate these two isomers have different functions on rat's CNV prevention and on HUVEC cell proliferation.

OBJECTIVE: To study the pharmacokinetic parameter and the relative bioavailability of ferulic acid in ordinary Guipi pills and ultramicro Guipi pills in rabbit.METHODS: HPLC-MS/MS was used to identify the concentration of ferulic acid in the blood sample.RESULTS: Plasma concentration of ferulic acid in ordinary pills was different from that in ultramicro pills.The main pharmacokinetic parameters of ferulic acid in ordinary pills vs.that in ultramicro pills were as follows:t1/2a:(17.59?2.57) min vs.(23.51?4.49) min;t1/2?:(300.91?38.74) min vs.(167.17?45.66) min;tmax: (9.61?1.69) min vs.(12.33?2.27) min;Cmax:(58.92?8.42) ng?mL-1 vs.(112.35?31.29) ng?mL-1;AUC: (5 851.67?895.49) ng?min-1?mL-1 vs.(8 586.13?1 497.62) ng?min-1?mL-1.There were significant difference in Cmax and AUC between ordinary pills and ultramicro pills.CONCLUSION: The application of super fine crushing technique in the preparation of Guipi pills could improve the bioavailability of Guipi pills.

Epithelial-Mesenchymal Transition ; Humans ; Sarcoma ; pathology

Objective To observe the effect of dexamethasone(Dex)on the proliferation and os- teogenic differentiation of human marrow stromal cells(MSCs)in vitro.Methods The primary human MSCs were isolated and cultured by Ficoll seperation culture in vitro.In subcultures,human MSCs were respectively treated with dexamethasone 10~(-9),10~(-8) and 10~(-7) mol/L.The proliferation of human MSCs was measured using MTF method;cytoplasmic alkaline phosphatase(ALP)activity was measured;the osteogenic marker osteopontin (OPN)mRNA were examined by reverse transcriptase polymerase chain reaction(RT-PCR).Results The op- tical density values in cultures treated with dexamethasone 10~(-8) and 10~(-7) mol/L for 8 days were significantly lower than those in the controls(P＜0.05).Treatment of cells with Dex for 12 days led to a significant increase in cytoplasmic ALP activity(P＜0.05)in a dose-dependent manner.Dex induced OPN mRNA.Conclusion Dex inhibits the proliferation of human MSCs and dexamethasone 10~(-7) mol/L leads to a strong decrease in cell number.Dex induces human MSCs differentiate to osteoblastic cells.

A lactoferrin-containing PEGylated liposome system (Lf-PLS) was developed and tested in vitro as a hepatoma-targeting drug delivery system. PEGylated liposomes (PLS) were successfully prepared using the thin film hydration method with peglipid post insertion. Lf was covalently conjugated onto the carboxyl terminal of DSPE-PEG2000-COOH on liposomes. Coumarin-6 was used to trace Lf-PLS with fluorescence. The cellular uptake of this system was carried out in asialoglycoprotein receptor (ASGPR) positive HepG2 cells via confocal microscopy and flow cytometry. The Lf-PLS liposome was observed as spherical or oval vesicles with the particle size around 130 nm, zeta potential about -30 mV and encapsulation efficiency more than 80%. The confocal microscopy images and flow cytometry data demonstrated that Lf-PLS resulted in significantly higher cell association by ASGPR positive HepG2 cells compared to PLS. The association between Lf-PLS and cells were dependent on the concentration, time and temperature, which was inhibited by pre-incubation with excessive free Lf. The results suggest that Lf-PLS has a good targeting effect on HepG2 cells in vitro. The targeting mechanism may be related to the specific binding of Lf and ASGPR on HepG2 cells, which guides Lf-PLS to the cell surface to induce an active endocytosis process. All these results demonstrated that Lf-PLS might be a potential drug delivery system in targeting hepatocellular carcinoma, which deserves more research on its targeting ability, antitumor efficiency, and metabolism in vivo for treatment of hepatomacellular carcinoma.
Asialoglycoprotein Receptor ; metabolism ; Carcinoma, Hepatocellular ; pathology ; Coumarins ; Drug Delivery Systems ; Endocytosis ; Hep G2 Cells ; drug effects ; Humans ; Lactoferrin ; pharmacology ; Liposomes ; Liver Neoplasms ; pathology ; Particle Size ; Phosphatidylethanolamines ; Polyethylene Glycols ; Thiazoles

AIM: To investigate the effects of myocardial remodeling of aged left atrium (LA) on atrial ar-rhythmogenesis in rabbits .METHODS:The male New Zealand rabbits were divided into young LA and aged LA groups . By observing the changes of monophasic action potential ( MAP) and burst-pacing in LA of the rabbits in vivo, the main cardioelectrophysiological parameters such as resting membrane potential ( RMP) , action potential amplitude ( APA) , ma-ximum rise veloctiy of action potential (dv/dtmax), plateau potential and action potential duration at 30%, 50%and 90%( APD30 , APD50 and APD90 ) , as well as the inducibility and duration of atrial arrhythmias were recorded .L-type calcium current (ICa,L) was analyzed via whole-cell patch-clamp technique in enzymatically dissociated single rabbit LA myocytes . The myocardial collagen content was quantified after Masson staining , and the ultrastructure of the LA cells was observed under scanning electron microscope .The expression of Cav 1.2 in LA tissue of the 2 groups was detected by Western blot . RESULTS:Compared with young LA group , dv/dtmax and plateau potential were significantly decreased , APD30 and APD50 were shortened, and APD90 was notably prolongated in aged LA group (P<0.01).The inducibility or duration of atrial arrhythmias was severely increased or prolongated in aged LA group (P<0.01).With voltage clamp model, the den-sity of ICa,L in aged LA group was significantly decreased , and current-voltage curve was notably moved upward compared with young LA group.When the clamp potential was +20 mV, the density of ICa,L was notably modified from (11.72 ± 1.39) pA/pF in young LA group to (6.08 ±0.98) pA/pF in aged LA group ( P<0.01).Compared with young LA group, the protein level of collagen was significantly increased (P<0.01), and the arrange of atrial myocytes was irregular in LA of rabbits in aged LA group .The atrial myocytes of the LA wall in aged LA group exhibited abnormal ultrastructural alterations , such as karyopyknosis , irregular and swelling mitochondria with the presence of vacuoles , and mild and severe sarcomere degeneration .Compared with those in LA tissues of young rabbits , the expression levels of Cav 1.2 in the LA tis-sues of aged rabbits were severely reduced (P<0.01), and had a significant positive correlation with the reduction of ICa,L (r=0.83, P<0.01).CONCLUSION:The pathophysiological characteristics of aged LA are significantly altered , and might contribute to vulnerability and susceptibility of occurrence of atrial fibillation in aged rabbits .The mechanisms might completely attribute to the notable reduction of ICa,L , abnormal alterations of ultrastructures and obvious decrease in the ex-pression of Cav1.2 in the aged LA of aged rabbits .

To introduce scientific research innovation into undergraduate education, cultivating innovative talents has been an urgent mission of current higher education. This article reviewed our experience, with the introduction of producing-studying-researching platform built on original innovative achievements of Chongqing medical university,of training physical medicine physician to be practical talents of large-scale diagnostic and therapeutic medical equipments, and was aimed to explore introducing producing-studying-researching platform into undergraduate education as well as improve personnel training quality of undergraduates.

Objective To investigate the clinical characteristics of infectious diseases of CNS.Methods Inpatients treated in the second hospital of Hebei Medical University from 1996 to 2005 were subjected to retrospective study.Results During 10 years,the hospitalization number of infectious diseases of CNS was 3929.The proportion of inpatients with viral meningitis(encephalitis),cerebral cysticercosis,tuberculous meningitis(TBM),purulent meningitis(PM)and cryptococcal meningitis(CM) was 63.8%,17.4%,7.7%,0.7% respectively.The hospitalization number of viral meningitis (encephalitis),TBM,PM and CM in the 2001—2005 5-year period was 53.5%,21.3%,35.3%,and 77.3% higher than that of the 1996—2000 period.Whereas the hospitalization number of cerebral cysticercosis decreased by 32.4% than that of the last 5 years.The peak months of viral meningitis (encephalitis)in a year were July,August and September.The peak months of TBM in a year were April, May and June.The case fatality of viral meningitis(encephalitis),cerebral cysticercosis,TBM,PM and CM was 8.1%,6.9%,22.4%,12.9%,33.3% respectively.Conclusions In the past l0 years,the incidence of common infectious diseases of CNS has increased in Shijiazhuang except cerebral cysticercoids. Our vigilance should be improved and some effective measures should be adopted to keep away infectious diseases of CNS.

Objective To investigate the meaning of expression of apoptosis related molecules NFKBp65 and p53 and GPX1-mRNA in patients with Keshan disease(KSD).Methods Sixteen chronic Keshan Disease patients were enrolled in KSD group according to electrocardiogram,chest X ray film and clinical examinations on 15,September in 2009,and 23 healthy people were included in control group from physical examination taken in The Second Affiliated Hospital of Xi'an Jiaotong University.Fresh blood(5 ml)was collected from antecubital vein of all subjects in the fasting state.Total mRNA and protein of blood sample were isolated using Trizol.GPX Assay Kit was used to detect GPX enzyme activity,and GPX1-mRNA expression was determined by SYBR Real-Time PCR.Meanwhile,expression of apoptosis related molecules NFKBp65 and p53 were determined by Western blot.Results GPX enzyme activity decreased significantly in KSD group[(108.61±14.10)U]compared with control group[(122.78±11.89)U,t=2.874,P<0.05],GPX1-mRNA level of KSD group(0.553±0.299)notably KSD group(0.802±0.057)compared with control group[(1.065±0.355),t=6.829,P<0.01].p53 increased in KSD group(1.604±0.191)compared with control group[(1.137±0.186),t=3.033,P<0.05].Conclusiom Decreased GPX1-mRNA expression may result in lower GPX enzyme activity of patients with KSD.Thus oxidative damage increases and cadioeyte apoptosis is activated by activating apoptosis signal pathway.