Objective:To establish and evaluate liver fibrosis model induced by bile duct ligation in mouse.Methods:The bile ducts of the mice were occluded by ligation.Serum AST,ALT,ALP,TBIL and DBIL were determined;the morphological observation was done by HE staining and Sirius red staining,expressions of ?-SMA and CK-19 were analyzed by immunohistochemistry staining;mRNA expression of ?-SMA and Collagen-1 in liver tissues were assayed by real-time PCR.A sham-operation group was used as a control.Results:Chocolate brown cells with positive expression of CK-19 and ?-SMA significantly proliferated 2 weeks after bile duct ligation.Serum AST,ALT,ALP,TBIL and DBIL levels of model group were much higher than those of control group;mRNA expression of ?-SMA and Collagen-1 in liver tissue by real-time PCR were increased significantly in model group.Conclusion:The mouse liver fibrosis model can be established successfully by bile duct ligation.

Aim: To establish a linear additive model for the predication of in vitro sinomenine hydrochloride release from the combination of immediate release, enteric-coated and sustained-release pellets based on the release profiles of each pellet type. Methods: Immediate release pellets were manufactured by extrusion/spher-onization technology. The operation of bottom-spraying in the fluid-bed equipment was conducted to enteric-coating using Eudragit~(R) L-30D-55 and sustained-release coating using Surelease~(R) . In vitro sinomenine hydrochloride release profiles of both uncoated and coated pellets were fitted to the chosen mathematical equations offered by the curve fitting toolbox of Matlab~(R) before a linear additive model was created based upon the best-to-fitting equations. The proportion of each pellet type in the combined format to generate the desired 24 h sinomenine hydrochloride release profile was solved by Matlab~(R). The predicted and assayed sinomenine hydrochloride release from the polled pellets was compared. Results: It was shown that the actual sinomenine hydrochloride release profiles of each pellet type were approximate to those of predicted ones. A linear additive model of the appropriate mathematical equations of each pellet was proven to be capable of controlling in vitro release of sinomenine hydrochloride multiple-unit pellets. Conclusion: A multiple-unit combined system of the selected pellets, as a novel sustained-release system, was successfully prepared. In vitro release performance of the calculated combination of each pellet type could be guaranteed by this approach in designing sustained-release drug delivery system.

This study is to prepare the microemulsion-based gel based on the W/O microemulsion and fluorouracil (5-Fu) as a model drug to study the transdermal characterization and observe its skin irritation of the microemulsion-based gel in vitro. IPM acted as oil phase, AOT as surfactant, Tween 85 as cosurfactant, water was added dropwise to the oil phase to prepare W/O microemulsion at room temperature using magnetic stirring, then 5-Fu powder was added. The gelatin was used as substrate to prepare 5-Fu microemulsion-based gel. The permeation flux of 5-Fu from 5-Fu microemulsion-based gel across excised mice skin was determined in vitro using Franz diffusion cell to study the influence of the amount of gelatin and the drug loading capacity. Refer to 5-Fu cream, the irritation of microemulsion and microemulsion-based gel on the rat skin was studied. Based on the water/AOT/Tween 85/IPM microemulsion, only the gelatin can form the microemulsion-based gel. At 25 degrees C, 32 degrees C and 40 degrees C, the amount of gelatin required for the formation of microemulsion-based gel were 7%, 14% and more than 17%, respectively. The 12 h transdermal cumulated permeation amount of 5-Fu from microemulsion-based gel containing 14% gelatin and 0.5% drug loading were (876.5 +/- 29.1) microg x cm(-2), 12.3 folds and 4.5 folds more than 0.5% 5-Fu aqueous solution and 2.5% (w/w) 5-Fu cream, respectively. Microemulsion-based gel exhibited some irritation, but could be subsided after drug withdrawal. Microemulsion-based gel may be a promising vehicle for transdermal delivery of 5-Fu and other hydrophilic drug.

AIM: To study the pharmacokinetics of oleanolic acid liposomes in rats.METHODS: Oleanolic acid liposomes were prepared by ethanol injection-sonication;The pharmaceutical properties including morphology,encapsulation efficiency,particle size,zeta potential were determined.Rats were injected with oleanolic acid lipo-somes and oleanolic acid solution via the tail,respectively.The plasma concentrations of sample in rats were assayed by RP-HPLC.The pharmacokinetic parameters were computered by 3P97 program package.RESULTS: Oleanolic acid liposomes showed almost spherical,the mean diametre was(206.4 ? 4.7) nm.The encapsulation efficiency of oleanolic acid liposomes could be more than 90% based on orthogonal design,and no haemolyticus existed.The plasma concentration-time curves of the oleanolic acid liposomes conformed to a two-compartment model.T1/2? of oleanolic acid liposomes was(33.59 ? 12.53) min,AUC was(240.13 ? 23.62)(?g/mL.min),obviously higher than that of the control preparation.CONCLUSION: The oleanolic acid liposomes with high entrapment efficiency and even size has a good pharmacokinetic parameters by comparison with non-liposomes.

Objective To investigate the protective effects of folic acid on the oxidative damage that ox-LDL (oxi?dized low-density lipoprotein receptor 1) render to human umbilical vein endothelial cells (HUVEC). Methods HUVECs were injured by ox-LDL (120 mg/L) for 24 h while they were incubated with various concentration of folic acid (0,15, 60, 150, 225, 300, 375 nmol/L). Then HUVECs were cultured in media contains same concentration of folic acid but without ox-LDL for 72 hours. Finally, HUVECs were harvested after 24, 48, 72 and 96 h. The morphological changes were observed us?ing inverted microscope and cell viability were examined by MTT. Results Various concentrations of folic acid (0,15, 50, 100, 200 and 500 nmol/L) has no obvious promotion or inhibition effect in growth of normal HUVEC (P>0.05). However, compared with the ox-FA-def group, 150, 225, 300 and 375 nmol/L of folic acid promoted proliferation of HUVECs with 96 and 120 hours of incubations (P < 0.05). Folic acid of 60, 150, 225, 300 and 375 nmol/L promoted the proliferation of HUVECs with 72 h and 96 hours of incubation (P<0.05). Conclusion High dose folic acid can reduce the ox-LDL oxida?tive damage on HUVEC in a concentration dependent manner.

Objective To study the effect of HCV receptors′sequence on virus entry based on the two-dimensional structure and via tandem expression of HCV receptors on mouse hepatocytes.Methods The construced recombinant expression vectors pCDH-hLDLR-hSR-BⅠ-hCD81-GFP, pCDH-hLDLR-hCD81-hSR-BⅠ and pCDH-hCLDN-1-hOCLN-DsRed were cotransfected into 293FT cells with package vectors.The collected recombinant lentivirus expressing hCLDN-1-hOCLN was concentrated and attacked mouse hepatocytes.The transgenic mouse hepatocytes with tandem overexpression of CLDN-1 and OCLN were established after G418-selection.The transduced cells LSCCO/Hepa1-6 and LCSCO/Hepa1-6 were sorted via flow cytometry and puro-G418-selection after recombinant lentivirus expressing hLDLR-hSR-BⅠ-hCD81 and hLDLR-hCD81-hSR-BⅠattacked Hepa1-6 respectively.The infectivity of transduced mouse hepatocytes LSCCO/Hepa1-6 and LCSCO/Hepa1-6 to HCV was analyzed via direct-infection of serum-derived virus.Furthermore, the effect of HCV receptors′sequence on virus entry was studied.Results Both LSCCO/Hepa1-6 and LCSCO/Hepa1-6 enhanced HCV-cell binding.The transduced mouse hepatocytes LSCCO/Hepa1-6 had more HCV endocytosis.Conclusion SR-BⅠhas priority over CD81 in HCV entry in the early stage.

Objective To explore humam cytomegalovirus(HCMV) encoded microRNAs during latent infection in order to help study HCMV virology and latent infection mechanisms.Methods A model of HCMV latent infection via THP-1 cells infected with HCMV was constructed.Deep-sequencing was performed using high-resolution Solexa sequencing platform.The secondary structure of the newly sequenced miRNA was predicted by RNAFold bioinformatics software. Results HCMV encoded various miRNAs during latent infection, including miR-US25-2-3p, miR-US25-2-5p, miR-UL112, miR-US25-1, miR-UL22A and PC-5p-148467 with a predicted length of 25 bp, named hcmv-miR-US33as-5p.Conclusion HCMV can express many types of miRNAs during latent infection.

Diabetes is an important risk factor for ischemic stroke. The glycated hemoglobin (HbA1c) level reflects the mean blood glucose level in the past 8-12 weeks. It is a detection index of abnormal glucose metabolism and chronic hyperglycemia. Some studies have shown that high HbA1c is associated with the poor outcomes of patients with acute ischemic stroke, including patients treated with intravenous thrombolysis and endovascular mechanical thrombectomy. This article reviews the relationship between HbA1c and the outcomes of patients with acute ischemic stroke.

Spontaneous intracerebral hemorrhage (ICH) has the highest rates of mortality and morbidity in stroke types.Experimental and clinical studies demonstrate that inflammatory reactions are early triggered by hematoma components,enhance the damage within the hemorrhagic brain,and influence the prognosis.Recent studied show that neutrophil to lymphocyte ratio (NLR),as an easily available biomarker to assess the systemic inflammatory status,has predictive roles in patients with ICH.This article reviews the predictive roles of NLR in patients with acute ICH.

The clot burden score (CBS) is a scoring method that quantifies the range of intracranial thrombosis in the anterior circulation ischemic stroke according to the location. Some studies have shown that CBS has predictive value for patients with acute ischemic stroke receiving reperfusion therapy, including functional outcome, vascular recanalization, and hemorrhagic transformation.