Objective:To optimize the clinical dosage regimen of amoxicillin and clavulanate potassium extended release ( ER) tablets based on the PK/PD parameters. Methods:Totally 30 healthy subjects ( half male and half female) were randomly divided into three groups, and orally administered the ER tablets respectively under fasting condition, before the meal and after the meal, and the optimal administration time was determined by comparing the pharmacokinetic characteristics. The subjects in the three groups were ad-ministered the ER tablets respectively at low, medium and high dosage, and the optimal dosage and dosing interval were determined based on the PK/PD parameters. Results:Under fasting condition, the AUC of amoxicillin [(32.2 ±15.0) μg·h·ml-1] was sig-nificantly lower than that before the meal [(41.7 ±1.92) μg·h·ml-1] and that after the meal [(42.6 ±17.7) μg·h·ml-1]. In contrast, the AUC of clavulanate acid after the meal [(1.89 ±0.54) μg·h·ml-1] was significantly lower than that under fasting condition [(2.55 ±0.76) μg·h·ml-1] and that before the meal [(2.58 ±0.76) μg·h·ml-1] (P<0.05). Amoxicillin and clavulanic acid displayed linear pharmacokinetics within the range of 1000-4000 mg and 62. 5-250 mg, respectively. After a single o-ral administration of amoxicillin and clavulanate potassium ER tablets at low, medium and high dose, the duration of blood concentra-tion above the minimum inhibitory concentration (MIC, 2. 0 μg·ml-1) (T> MIC) in 12 h was 5. 5, 7 and 10 h, and the percentage was 46%, 58% and 83%, respectively, and T> MIC in 12 h was 4. 5, 6 and 8 h, and the percentage was 38%, 50% and 67%, re-spectively when MIC was 4. 0μg·ml-1 . Conclusion:It is suggested that amoxicillin and clavulanate potassium ER tablets be taken at the start of a standard meal, 2 tablets per time, twice daily, which is sufficient to achieve T> MIC of 40% -50%.

ObjectiveTo investigate the role of 15-F2t-isoprostane in intestinal injury induced by intestinal ischemia/reperfusion (I/R) in rats.MethodsThirty-two pathogen free adult male SD rats weighing 230-255 g were randomly divided into 4 groups ( n =8 each):group sham operation (group S) ; group intestinal I/R; group SQ-29548 (TXA2 receptor antagonist) (group SQ) and group DMSO (the solvent).Intestinal I/R was induced by 60 min occlusion of superior mesenteric artery (SMA) followed by 120 main reperfusion in groups I/R,SQ and DMSO SQ-29548 2 μmol/kg and DMSO were injected subcutaneusly at abdominal wall at 30 min before SMS in groups SQ and DMSO respectively.Arterial blood samples were taken at 120 min of reperfusion for determination of serum diamine oxidase (DAO) activity and 15-F2t-isoprostane,endothelin-1 (ET-1) and thromboxane B2 (TXB2) concentrations.Intestinal tissues were removed for microscopic examination and determination of myeloperoxidase (MPO) and SOD activities,MDA and lactate contents.Intestinal damage was assessed and scored according to Chiu (0 =normal,5 =disruption of tunica propria,bleeding and ulceration).ResultsIntestinal I/R significantly increased Chiu's score,MDA and lactate contents and MPO activity and decreased SOD activity in intestine in group I/R as compared with group S.SQ-29548 pretreatment significantly decreased Chiu's score,lactate content and MPO activity in intestine and increased intestinal SOD activity and decreased serum DAO activity and ET-1 concentration in group SQ as compared with group I/R.Conclusion15-F2t-isoprostane is involved in the development of intestinal injury induced by intestinal I/R by activating TXA2 receptor,increasing ET-1 production and promoting neutrophil infiltration.

Objective To investigate whether perfusion-weighted imaging (PWI) can be used to evaluate blood perfusion of patients with leukoaraiosis (LA), its relationship to clinical features, and the therapy effect of LA. Methods The 44 patients with LA were recruited in the study. All the subjects were examined with both conventional and dynamic susceptibility contrast-enhanced perfusion MR imaging, 13 of them repeated the examinations after the treatment. The shapes and sizes of the biggest lesions in each patient were confirmed by conventional MR imaging, then the values of relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF) and relative mean transit time (rMTT) in each lesion were calculated respectively. Furtherly, a Pearson's correlation analysis was performed to show whether these values were correlated with mini-mental state examination (MMSE)scores or activities of daily living (ADL) scores. Results The 44 lesions of all the subjects showed significant decreases in rCBV (0. 797 ± 0. 160) and rCBF (0. 779± 0. 164) but increase in rMTT (1. 029±0. 073). There were positive correlations between rCBV and MMSE (r = 0. 524, P =0. 000), between rCBV and ADL (r=0. 621, P=0. 000), between rCBF and MMSE (r=0. 555, P=0. 000), and between rCBF and ADL (r= 0. 690, P= 0. 000), and negative correlations between rMTTand MMSE (r=-0.307, P=0.043), and between rMTT and ADL (r=-0.434, P=0. 003). The blood perfusion was enhanced in 10 out of 13 patients who received the repeated examinations after the treatment, most of whom showed the improvement of clinical symptoms.Conclusions Perfusion MR imaging can assess hemodynamic alterations in LA, which could reflect the clinical symptoms. Moreover, the changes of blood perfusions can be used to evaluate and monitor the therapy effect of LA.

Objective To identify the Banna viruses isolated in northwestern part of Yunnan prov-ince in order to make the difference clear between the isolates and other Banna viruses isolated in other parts of Yunnan. Methods Three isolates of Banna vires isolated in 2005 and 2006 were identified by morpholo-gy, RNA-PAGE profile and molecular biologic method. Nueleotide and amino acid sequences of segment 12 of the 3 isolates were sequenced and analyzed. Results Three Banna viruses were isolated from mosquitoes collected in northwestern part of Yunnan during 2005 and 2006. Electron microscopy study showed that they are spherical with a diameter of 70 nm, no envelope but two layers of eapsid. It was found that the genome of the 3 isolates composes of 12 segments presenting band profile of 6-6 in RNA-PAGE. Nueleotide acid se-quence analysis about segment 12 showed that the identity was 99% between the 3 new isolates, 98% and 90% between the 3 isolates and the strains isolated in other parts of Yunnan, China and Indonesia, respec-tively. Phylogenetie analysis based on segment 12 gene showed that 3 new isolates clnstered in the same branch with the viruses isolated in other parts of Yunnan. The same difference of amino acids was found between Banna viruses isolated in China and Indonesia strains in the analysis of segment 12. Conclusion Banna virus strains were firstly isolated from mosquitoes collected in northwestern part of Yunnan province. Nueleotide acid sequence analysis of the 3 new isolates showed higher identity with strains isolated in other parts of Yunnan.

Objective To investigate the CT and MRI features and morphology classification of intraductal papillary mucinous neoplasm of the bile duct (IPMN-B).Methods A total of 18 patients with IPMN-B proved by pathology were retrospectively analyzed.Out of 18 patients,16 patients underwent enhanced and non-enhanced CT,13 underwent contrast enhanced MR,and 11 out of 13 underwent both CT and MRI.IPMN-B was classified into 4 types:typical IPMN-B,cystic-forming IPMN-B,non-tumor IPMN-B and invasive IPMN-B,according to imaging findings and gross pathological findings.Results Typical IPMN-B (9 cases):tumors were distributed along the bile ducts,both upstream and downstream bile ducts were obviously dilated.Cystic-forming IPMN-B (5 cases):single or multiple tumors were found in aneurysmal dilatation of bile ducts.Non-tumor 1PMN-B (2 cases):no mass was found in the widely dilated bile ducts with smooth bile duct wall.Invasive IPMN-B (2 cases):tumors protruded into the dilated bile ducts causing jagged wall of bile duct,with accompanied abnormal density or signal intensity outside the bile ducts.Bile duct dilatations were shown in all 18 cases,and tumors were shown in 16 cases.In 2 cases no mass was displayed in widely dilated bile ducts.CT density of the tumor was lower than that of liver parenchyma,and higher than that of the bile and intraductal mucin.Signal intensity of the tumor was higher than that of stones,and lower than that of bile and intraductal mucin at MR T2WI.All tumors showed high intensity on DWI.Tumors showed mild to moderate enhancement after injection of contrast agent,CT density or signal intensity of the tumors were lower than that of the liver parenchyma during all three phases of contrast-enhanced CT or MRI.Conclusion IPMN-B has some specific CT and MR imaging features,which are helpful for the diagnosis and classification of IPMN-B.

BACKGROUND: Mesenchymal stem cells (MSCs) are an important component of the in vivo microenvironment and act on multiple biological behaviors of tumor cells. The potential clinical value of MSCs has become an issue of concern in recent years.OBJECTIVE: To investigate the gene expression profiles of acute promyelocytic leukemia (APL) cell line NB4 treated with umbilical cord-derived MSCs (UC-MSCs) using cDNA microarray.METHODS: In vitro co-culture system was constructed, and then cellular proliferation, apoptosis and differentiation status of NB4 cells treated with UC-MSCs were evaluated. Two cDNA probes were prepared through reverse transcription from mRNA of NB4 cells treated with or without UC-MSCs. The probes were labeled with fluorescence dyes individually, hybridized with cDNA microarray, and their fluorescent intensities were scanned. The genes were screened through the analysis of the difference in two gene expression profiles.RESULTS AND CONCLUSION: UC-MSCs promoted the proliferation and differentiation, while reduced the apoptosis of NB4 cells. The analysis of gene expression profiles indicated that after co-culture with UC-MSCs, 530 genes were up-regulated and 53 genes were down-regulated. Accordingly, specific gene function and pathway signaling related were also regulated to some extent. Overall, UC-MSCs influence can major biological behaviors of NB4 cells by changing expression of a large amount of genes, gene-related function and multiple intracellular signaling pathways.

ObjectiveToll-like receptors (TLRs) play important role in the progression and tumor immunity of some types of cancer,some research have demonstrated that agonist of TLR3 can trigger apoptosis of cancers.This study was proposed to investigate if Poly(I:C),the specific agonist of TLR3,could impact proliferation or apoptosis of progressive breast cancer cells MDA-MB-231,and to investigate the primary mechanism of the function.MethodsExpression of TLR1-10 mRNA was detected by quantitative real-time reverse transcription-polymerase chain reaction.Cell Counting Kit-8 was used to determine the inhibitory effect of Poly(I:C) on proliferation of MDA-MB-231 cells.Cell apoptosis was assayed by flow cytometry with V-FITC/PI staining.Results First,the toll-like receptors 1-10 were all expressed on MDA-MB-231 cells,while the expression level of TLR8 was lower than that of others.Second,according to the CCK-8,the proliferation of MDA-MB-231 cells was inhibited,but the apoptosis was not affected on the basis of Apoptosis Kit.At last,the mRNA expression of TNF-α、IFN-β and IFN-γ were elevated approximately 20 times after Poly(I:C) stimulation for 6 hours.ConclusionMDA-MB-231 cells express all toll-like receptors on mRNA level,and TLR8 was expressed lower than others.The stimulation of TLR3 with Poly(I:C) can inhibit the proliferation of MDA-MB-231,but had no effect on apoptosis.TNF-α、IFN-β and IFN-γ maybe participate in this process.

Objective To analyze the genotype of Japaneso encephalitis virus (JEV) strains isola-ted in 2004 from mosquitoes collected in Bazhong city, Sichuan province of China, and the characters of amino acid in the PrM and E gene. Methods The isolated virus strains from mosquitoes were identified by biological, serological and molecular biology. PrM and E segments of the isolated JEV were amplified by RT-PCR, the PCR products were purified and sequenced. Multiple alignment, phylogenetic and amino acid (AA) analysis were carried out by Clustal X (1.8) , MEGA4 and GENEDOC (3.2) . Results The total of 4688 mosquitoes were collected including Armigeres and Culex. Six isolates were identified be-longing to genotype 1 JEV. The comparison between new genotype 1 JEV strains and live attenuated vaccine strain SA14-14-2 in PrM and E gene showed that total 3 sites amino acid differences in PrM gene and 14 sites in E gene, respectively. Three sites (PrM2, 64 and 65 ) in PrM protein and four sites (E129, 222,327 and 366) in E protein were only belonging to genotype 1 JEV. Conclusion The new isolated JEV strains in Sichuan province belong to genotype 1. It suggests that the vaccine strain SA14-14-2 currently used for preventing Japanese encephalitis is able to protect people against JEV, although in the segments of it had some amino acid differences between vaccine strain and the epidemic genotype 1 JEV strains in PrM and E gene.

The Flanders virus (FLAV) is a number of family Rhabdoviridae ,contains a single‐stranded ,negative‐sense vi‐ral RNA .Here we describe a molecular detection method developed for fast measurement of FLAV based on Taqman RT‐PCR method .In this study ,FLAV specific primers and probe were designed based on the FLAV L gene sequences published in GeneBank .Quantitative standard curve of FLAV TaqMan PCR was also successfully established .The specificity and stability test showed that the system is specific and the coefficient variables were all less than 1 .7% .Quantitative standard curve based on the genomic copy was drawn ,and the lowest detectable limit (LOD) of system was 100 copies/PCR ,with higher sensitivity and stability than that of the conventional RT‐PCR assay targeting the same gene .

In order to investigate the molecular evolution and spatio-temporal migration of Getah viruses (GETV) isolated around the world,the nucleotide and deduced amino acid sequence of GETVs were analyzed and phylogenetic trees were constructed by using informatics software including ClustalX1.83,MegaAlign,GeneDOC and Mega6.0.The Bayesian Stochastic Search Variable Selection (BSSVS) program in the BEAST v 1.8.1 software package was used to analyze the spatial dynamics of the Getah virus.Results showed that the full-length of Getah virus E2 gene consists of 1 266 nueleotides,encoding 422 amino acids.And the homology of nucleotide and amino acid were 94.5％ 100％ and 96.4％ 100％ respectively.The molecular evolution analysis revealed that there were no species and geographical distribution difference existing among GETV host animals (e.g.horses and pigs) and vectors (e.g.mosquitoes).Bioinformatics analysis showed that GETV originated in Malaysia,then it was spread to Japan,China,South Korea,Mongolia,Russia,etc.GETV E2 gene was relatively stable since GETV was first isolated in 1955.The differences of species and geographical distribution did not exist among GETV host animals and vectors,and the virus has spread from tropical regions to Eurasian continent.Thus,strengthening the detection and monitoring of GETV and its infections in humans and livestock is critical.