Arteriovenous fistula (AVF) and arteriovenous malformation (AVM) are the common intracranial vascular malformations. The experimental models of AVF and AVM include animal models, in vitro models and biomathematical models. These models could be used to investigate the pathophysiological characters of AVF and AVM, to simulate the clinical treatment, and to examine the materials for embolization therapy. This article reviewed the formation of these models, evaluated their advantages and disadvantages, and briefly introduced their applications.

Objective:To study the characteristics of the adverse reactions caused by tacrolimus and analyze the risk factors. Methods:Totally 280 cases of renal transplant recipients received standard treatment options were selected from 1997 to 2013 in Wuhan general hospital of Guangzhou military command. The tacrolimus-related adverse reactions and their risk factors were analyzed statistically. Results:Totally 39. 65% of the patients had the tacrolimus-related adverse reactions. The main adverse reactions were hematotoxicity,diabetes mellitus and hyperlipidemia. The univariate analysis showed that age,weight,BMI and treatment course were the suspected risk factors. The multivariate analysis results showed that age,BMI and treatment course were the risk factors of tacrolimus-related adverse reactions. Conclusion:The incidence of tacrolimus-related adverse reactions is relatively high,and if the patient is in advanced age,with poor nutritional status or long-term medication,the probability of adverse reactions will be increased.

Objective To offer a theory that supports the individualized tacrolimus dosage regimen by retrospectively investigating the influences of gene polymorphism and other clinical factors on tacrolimus concentration in renal transplant recipients. Methods A total of 280 renal transplant recipients were genotyped for CYP3A4?5, CYP3A4?6, CYP3A4?18B, CYP3A5?3, MDR1 1236C>T, MDR1 2677G>T/A, MDR1 3435C>T polymorphisms by PCR followed by restriction fragment length polymorphism (RFLP) analysis.PXR 6bp deletions (rs3842689) genotypes were determined by Allelic Special-Touch down PCR.Correlation between gene polymorphisms and tacrolimus concentrations was analyzed. Results The mutation frequency of CYP3A4?18B, CYP3A5?3, MDR1 1236C>T, 2677G>T/A, 3435C>T and PXR rs3842689 in the renal transplant recipients was 29.11%, 69.29%, 43.57%, 49.64%, 36.43% and 26.07%, respectively.Multiple regression analysis showed that, CYP3A5?3 and red blood cell count were associated with the value of C0/D of FK506, the best regression model was:D=C0/(-60.445 +95.777×CYP3A5 +34.938×RBC), and the equation could explain 38.8% of tacrolimus individual differences. Conclusion Gene polymorphism of CYP3A5?3 and red blood cell count may be responsible, in part, for the large interindividual variability of FK506 dose and concentration.

Objective To investigate the effect of fenofibrate on the matrix metalloprotenase-9 (MMP-9) expression and the proliferation of cultured human umbilical vein endothelial cell (HUVECs) induced by oxidized low density lipoprotein(ox-LDL-C).Methods HUVECs cultured in vitro at passage 4 to 9 were used for the experiment.They were divided into control group,ox-LDL-C group (100 mg/L) and ox-LDL-C + fenofibrate group.The cells in ox-LDL-C + fenofibrate group were firstly incubated with 10,50,100 μmol/L fenofibrate respectively for 6 h,then incubated with 100 mg/L ox-LDL-C for another 24 h.MMP-9 expression in supernatant medium was detected by enzyme-linked immuno sorbent assay (ELISA) and cell proliferation was measured by MTT assay.Results Compared with the control group,ox-LDL-C (100 mg/L) could inhibit the proliferation of HUVECs (P ＜ 0.01) and promote the production of MMP-9 of HUVECs.Fenofibrate could inhibit the proliferation of HUVECs induced by ox-LDL-C in a dose-dependent manner (P ＜ 0.01).Fenofibrate (10,50,100 μmol/L) could significantly stimulate the production of MMP-9 of HUVECs induced by ox-LDL-C (P ＜ 0.01).The stimulation effect was dose-dependent.Conclusion Fenofibrate can inhibit the production of MMP-9 in HUVECs induced by ox-LDL-C,promote the proliferation of HUVECs and protect endothelial function in a dose-dependent manner,then may play the role of anti-artherosclerosis besides lipid regulation.

Objective To investigate chromosomal gains and losses in association with human papillomavirus status in the vulvar squamous cell carcinomas(VSCC). Methods We analyzed 21 VSCC with comparative genomic hybridization (CGH) and polymerase chain reaction.Results Each case had different degree of variances, including gains and losses of partial or whole chromosome. On average, each case had 4.9(102/21) abnormal regions; losses were more than gains, being respectively 2.6(54/21) and 2.3(48/21). Main variations were gains on chromosomes 3q(43%,9/21),8q(38%,8/21),12q(33%, 7/21 )and 9p(19%,4/21),and losses of 4p(52%,11/21),3p(43%,9/21)and 9p(10%,2/21).Gains of 3q(73%) and 12q(64%) were significantly more common in human papillomavirus (HPV)-positive VSCC compared to HPV-negative VSCC(10%,0;P

Objective To investigate a panel of differentially expressed circulating microRNAs (miRNAs) as potential biomarkers in patients with systemic lupus erythematosus (SLE).Methods A miRNA array was performed on plasma of 10 healthy controls and 10 SLE patients.To confirm the results of microarray,the selected 7 miRNAs were examined by real-time quantitative PCR (RT-qPCR).Independent sample's t-test was used for statistical analysis between the two groups.Results A total of 51 circulating miRNAs were signi-ficandy differentially expressed between SLE patients and healthy controls (19 up-regulated miRNAs and 32 down-regulated miRNAs).The findings of RT-qPCR on 7 miRNAs (miR-126,miR-21,miR-223 and miR-451 of upregulation and miR-125a-3p,miR-146a and miR-155 of down-regulation) were consistent with the data obtained from the array.Conclusion There is aspecific circulating miRNAs expression profile in SLE,and these aberrantly expressed miRNAs might have great potential to serve as novel,noninvasive biomarkers of SLE.

Objective:To investigate the distribution and evolution of immunocytes in infantile hemangioma(IH).Methods:Fifty-two infantile hemangioma samples were investigate.The distribution of CD3+T cells,CD8+T cells and S-100+dendritic cell(DC) in IH was observed with.Results:CD3+T cell was not found among the earliest IH.In the middle proliferating stage,the number of CD3+T cells increased;But the CD8+T cells were still scare.In the late proliferating stage,there were many CD3+T cells and the number of CD8+T cells also increased.In the early involuting stage,there were still a number of CD3+ and CD8+ T cells around the microvessels.In the middle involuting and involuted stage,only a few of CD3+T cells and CD8+ T cells existed.In the early proliferating stage,there were some DC in IH.During the middle and late proliferating stage,the number of DC increased significantly.Since the early involuting stage,the DCs decreased rapidly and disappeared.Conclusion:The distribution of T cells and its subsets and DC have close relationship with the pathologic evolution of infantile hemangioma.

Objective To establish a sensitive method for the determination of rhodamine 123 (Rh123) in rat plasma by high performance liquid chromatography (HPLC).Methods The plasma samples were extracted by acetonitrile,and then separated on a Hypersil BDS C18 colunm (4.6 mm×100 mm,5 μm) equipped with a guard column kept at 25 ℃.The mobile phase consisted of acetonitrile and phosphate buffer (0.02 mol·L-1,pH4.0) (60:40) and was pumped at a constant rate of 1.0 mL·min-1.The peak was detected using a fluorescence detector set at FLD1A:Ex=485 nm,Em=546 nm.Results In this study,the method was validated for the Rh123 range of 0.1 to 32.0 μg·L-1,and the lower limit of quantitation (LLO Q) was 0.1 μg·L-1.The intra-and inter-day precisions for Rh123 were less than 7%,and the mean recoveries of Rh123 were 87.93%,89.03%,86.11% at low,mid,and high concentrations,respectively.Conclusion A simple,rapid and reproducible HPLC method was developed for the determination of Rh123 in rat plasma,which was an applicable method in modeling and description of the possible pharmacological interactions between the medicines and P-glycolprotein transporter.

Objective To observe the expressions of NeuN and pCaMKⅡα in brain and test the spacial learning and memory in neonatal hypoxic?ischemia encephalopathy ( HIE ) model mice. Methods 7d ICR mice were randomly divided into sham group( n=19) and model group( n=23). HIE model was induced by right common carotid artery ligation followed by 8% oxygen hypoxia for 100 min. DAPI staining was used to examine brain pathological change,immunofluorescent staining was used to examine the expression of NeuN and pCaMKⅡα in the ipsilateral brain,and Morris water maze was used to test the spa?cial learning and memory. Results Mice in sham group showed that brain cells were arranged in a dense and orderly manner,the number of NeuN?positive cells and pCaMKⅡα?positive cells were (106.50±20.07), (87.17±16.55) respectively in the brain,and the escape latency was short. Compared with mice in sham group,mice in model group showed more cells loss,less NeuN?positive cells(19.17±3.60) and less pCaMKⅡα?positive cells(13.33±3.62) in the ipsilateral hemisphere,and longer escape latency(P<0.01). Conclu-sion The spacial learning and memory are impaired in hypoxia ischemia,which may be related to the de?creasing expression of pCaMKⅡα in neurons in ipsilateral brain.

Objective To examine the effect of berberine hydrochloride ( BER ) on the pharmacokinetic profiles of midazolam,a substrate of CYP3A,in rats. Methods The rats were intragastrically given different doses of BER (50,100, 200 mg?kg-1) or ketoconazole (75 mg?kg-1) for 10 days.Single-pass duodenum perfusion of 20 mg?kg-1 MDZ was performed and the inguinal artery was cannulated for blood sampling.Plasma concentrations of MDZ and 1'-OH-MDZ were analyzed by high performance liquid chromatography ( HPLC) with the CYP3A inhibitor ketoconazole serving as positive control. Results BER (50,100,200 mg?kg-1) and ketoconazole (75 mg?kg-1) could significantly increase the AUC(0-t),AUMC(0-t)and Cmax of MDZ in a dose-dependent manner ( P<0.05) ,and reduce the clearance rate ( CLz ) of MDA and its apparent volume of distribution in the body ( Vz ) ( P<0. 05). But they failed to dramatically affect the half-life ( t1/2z ) and the peak time ( tmax ) of MDZ. Additionally,BER ( 100,200 mg?kg-1 ) and ketoconazole ( 75 mg?kg-1 ) could significantly dose-dependently decrease the AUC(0-t),AUMC(0-t)and Cmaxof 1'-OH-MDZ,and profoundly increase the CLz,tmax and Vz of 1'-OH-MDZ (P<0.05),but they had no remarkable influences on the t1/2z.The ratio of AUC(1'-OH-MDZ)/AUC(MDZ) was decreased with the increase of BER concentration. Conclusion BER can inhibit the in vivo metabolism of MDZ in a dose-dependant manner, which is associated with the suppression of the activity of CYP3A.