0.05), but there is statistic difference between the two groups in estimating the involvement of cervical canal and the earlier surgical stage than clinical stage(P

OBJECTIVE:To study the pharmacokinetic characteristics of triflusal capsule in healthy volunteers. METHODS:In ran-domized test,36 healthy volunteers were randomly divided into 3 groups. They were given low-dose,medium-dose and high-dose of Triflusal capsule(300 mg,600 mg and 900 mg),qd,for one day,and then pharmacokinetic study of single dose of Triflusal capsule was conducted;Triflusal capsule medium-dose group was continuously given medicine for 13 days,and then pharmacokinetic study of multiple dose of Triflusal capsule was conducted. The plasma concentration of triflusal was determined by LC-MS/MS,and Zorbax SB-C18 column was used with methanol-0.2% formic acid (80:20,V/V) at the flow rate of 0.2 ml/min. ESI was adopted in MRM mode,negative ion detection was carried out,quantitative analysis m/z 247.1→161.1(triflusal),m/z 294.0→250.0(internal standard, diclofenac sodium). Pharmacokinetic parameters were calculated by using WinNonlin 6.2 software,and the difference of them were compared. RESULTS:The linear range of triflusal were 0.05-20 μg/ml. The main pharmacokinetic parameters of triflusal capsules high-dose,medium-dose and low-dose groups were as follows:t1/2 were (0.45 ± 0.20),(0.47 ± 0.10),(0.43 ± 0.20) h;tmax were (0.56±0.20),(0.60±0.20),(0.47±0.40)h;cmax were(3.30±0.98),(10.65±3.26),(13.96±4.88)μg/ml;AUC0-8 h were(3.99±0.93), (13.29±1.72),(19.62±6.78)μg·h/ml;within dose of 300-900 mg,linear relationship was found between cmax,AUC0-8 h and dose(R2=0.954,0.986). When reaching stable state of multiple dose,average blood concentration was(0.71±0.20)μg/ml;main pharmacokinetic parameters were as follows:AUCs(17.10±4.82)μg·h/ml,t1/2(0.49±0.10)h,tmax(0.85±0.62)h,cmax(11.58±3.99)μg/ml,AUC0-8 h (16.99±4.84)μg·h/ml,AUC0-∞(17.08±4.81)μg·h/ml;accumulation factor(1.28±0.40). tmax and t1/2 of single dose were similar to those of multiple dose. CONCLUSIONS:LC-MS/MS can determine the content of triflusal in human plasma rapidly and accurately, and accumulation phenomena exist in healthy Chinese volunteers,which shows linear pharmacokinetic characteristics.

Objective To assess the right ventricular (RV) performance in patients with type 2 diabetes mellitus (2-DM) by two-dimensional speckle tracking imaging (2D-STI),and to explore the clinical value of RV longitudinal strain and strain rate.Methods Thirty-seven patients with 2-DM only and thirtyone patients coexisting diabetes and hypertension (DM + HTN) were studied.Thirty-nine healthy age matched persons served as control subjects.In each patient a conventional two-dimensional echocardiography was performed and also an echocardiographic study with strain/strain rate imaging was studied.Analysis of RV longitudinal systolic strain were obtained in the apical four-chamber view of the RV for the assessment of the RV free wall(F-PLSS),interventricular septum (S-PLSS) and the global RV wall (G-PLSS).The entire RV longitudinal peak systolic strain rate (G-SRs),peak early-diastolic strain rate (G-SRe) and peak late-diastolic strain rate (G-SRa) were performed in the apical four-chamber view.Results Compared with controls,F-PLSS,S-PLSS,G-PLSS,G-SRs and G-SRe were decreased in 2-DM and DM + HTN (all P ＜0.01),with lower values in DM + HTN (P ＜0.05).In the patients coexisting diabetes and hypertension,G-SRa was significantly lower than those in the control group (P ＜ 0.05).Compared with 2-DM,this difference was not significant in controls and DM + HTN (P ＞0.05).Conclusions No matte the patients of 2-DM with or without hypertension,the early changes of RV dysfunction can be found by 2D-STI.Patients coexisting diabetes and hypertension may have worse RV dysfunction.

Objective To study the clinical characteristics and prognosis of children aged 5 or above with stage 3/4 neuroblastoma ( NB).Method Among 180 children with NB admitted from March 2007 to June 2015, 54 were aged 5 or above with stage 3 or 4.The clinical characteristics , therapeutic efficacy and prognosis of above 54 cases were analyzed.Results There were 36 boys and 18 girls with a male to female ratio of 2∶1.The most common of primary site was retroperitoneum (41/54, 75.5%), followed by mediastinum (10/54,18.5%), spine and pelvic cavity (3/545,6%).After treated by average 9 cycles of chemotherapy , 34 cases ( 63%) achieved complete remission ( CR ) , 13 ( 24.1%) achieved partial remission (PR), 5 (9.3%) presented disease progression (DP), and 2 died (3.7%).Patients were followed up for median 30 months ( 8 -99 months ) , 24 cases died and 30 survived with a overall survival (OS) rate of 55.6%.In 30 survival cases, there were 23 cases (76.7%) of event-free survival (EFS) ,and 6 cases (20.0%) of PR and 1 case (3.3%) of DP.There were significant differences in prognosis among patients with different responses to first therapy (χ2 =8.963, P =0.003 ).Among 20 children with stage 4 NB treated by autologous peripheral blood stem cell transplantation ( APBSCT ) , 13 cases died and 7 survived with an average survival time of (73.55 ±8.89)months.Among 29 cases without APBSCT, 11 cases died and 18 survived with an average survival time of(40.19 ±5.52)months.There was no significant difference in survival between APBSCT and no-APBSCT.Conclusion Children aged 5 or above with NB tend to have advanced stage , relapse and long treatment cycle , but the survival still can be improved with the appropriate treatment .

Objective To systemically evaluate the accuracy of CT and MR estimating whole liver volume with evidence based medicine methods.Method Published papers about whole liver volume estimation with CT or MR modality were searched in Cochrane library,MEDLINE,EMBASE,CMBdisc(China biology medicine disc) for English and Chinese abstracts.Inclusion criteria were formulated according to validity criteria for diagnostic research published by the Cochrane collaboration.Heterogeneity test of extracted data of Eligible papers was performed first to determine the appropriate statistical model used to pool the result.Finally,sensitivity and publish bias analysis was performed.Result Seventeen articles with 37 studies including 351 patients met the inclusion criteria.There was no heterogeneity between included studies (I2 =0％,Q =5.85,P =1).Fixed effect model was selected for the meta analysis and there was no statistically significant difference between true and radiological estimated whole liver volume (WMD =21.61 mL,95％ confidence interval:-6.33-49.57 mL,z =1.51,P =0.13).Sensitivity analysis revealed the result was robust which was not affected by excluding any of the included studies.Funnel plot and publish bias analysis showed no publish bias (t =-1.55,P=0.13).Conclusion CT and MR volume estimation is accurate for liver volume measurement,which provides important information for preoperative evaluation,postoperative monitoring and follow-up studies of other hepatic pathologies.aximum benefit to patients.

Objective To determine the function of conserved amino acids in the fusion-promoting domain of Newcastle disease virus (NDV) hemagglutinin-neuraminidase (HN) protein,clearly understanding mechanism of cell fusion.MethodsUsing a PCR-based site-directed mutagenesis method and the method of homology recombination occurred in vivo to change six conservative amino acids into alanine respectively.Wild type (WT) and all mutant HN proteins were exepressed in BHK-21 cells by the vacciniaT7 RNA polymerase expression system.The amount of each HN protein at the cell surface was determined by fluorescence-activated cell sorter (FACS).Cell fusion efficiency,hemadsorption activity (or receptor binding activity) and neuraminidase activity were determined.Results There was no statistic difference of cell surface expression among WT and each mutant HN protein ( P＜0.05 ).Cell fusion efficiency of each mutant protein decreased to some extent,especially 1103A decreased to 14.2％ in head.Hemadsorption activity of mutant proteins were reduced in different extent,the maximum reduction of which was also 1103A,28.2％ of wt NDV HN.There was different neuraminidase activity among each mutant HN protein.L74A increased slightly to 118.6％.L110A decreased most to 5.2％.I103A decreased second most to 5.7％.Conclusion Conserved amino acids in fusion-promoting domain of NDV HN played an important role in cell fusion.I103 was identified as a key amino acid in this domain.

OBJECTIVE:To compare the effects of prophylactic application of 3 different antibiotics on prognosis in patients underwent breast lesion resection. METHODS:1 066 patients with breast lasion resection from 12 hospitals of Shaanxi province were divided into trial group(360 cases),control group A(352 cases)and control group B(354 cases)according to random num-ber table. Trial group was given first generation cephalosporin cefazolin;control group A was given second generation cephalospo-rin cefuroxime;control group B was given third generation cephalosporin cefoperazone sodium and tazobactam sodium. The dosage regimens of 3 groups were as follows:relevant drug 2 g added into 0.9%Sodium chloride injection 100 ml,ivgtt,0.5 h before sur-gery,medication course≤24 h after surgery in trial group. Those indexes of 3 groups were observed,such as post-operative ADR, incision healing,infection,hospitalization duration,phamaceutical costs per capita. RESULTS:There was no statistical signifi-cance in the rate of incision healing and the rate of post-operative infection among 3 groups(P>0.05). The incidence of post-opera-tive ADR,hospitalization duration and phamaceutical costs per capita in observation group were significantly lower or shorter than in control group A and B,with statistical significance(P<0.05). CONCLUSIONS:Cefazolin is better than cefuroxime and cefo-perazone sodium and tazobactam sodium to reduce the postoperative adverse reaction,antibiotics cost per capita and hospital drug cost per capita,shorten the hospitalization duration.

Objective To study the variation and characteristics of HIV-1 tat exon 1 gene from a patient with AIDS dementia complex( ADC), so as to research the pathogenesis of ADC. Methods The tat gene was amplified with nested PCR from genomic DNA which was extracted from lymph node, spleen and different brain tissues( meninges, grey matter from frontal cortex, white matter from frontal cortex, temporal cortex and basal ganglia) of a patient who died of ADC. PCR products were cloned into the pGEM-T vector,after transformation and selection by ampicillin and blue/white spotting. Five of positive clones were sequenced. HIV-1 tat sequences were processed with BioEdit and MEGA4. With the softwares, Neighbor-Joining tree, p-Distances, values of ds/dn, and analysis of amino acid motifs were all done. Results The samples were all identified as HIV-1 B and genetic variation exists in HIV-1 tat isolated from different tissue;Compared with HXB2, sixteen sites of the amino acid seque nce coded by the HIV-1 tat gene which was isolated from the patient changed. In addition, part of the changes were different between periphery and brain,especially, the five Q54R changes from basal ganglia and one Q54R change from temporal cortex are deserve to follow with interest. Conclusion Variations exist in the HIV-1 tat genes extracted from the ADC patient and the variations from peripheral and central nerve tissues were different, whether the variations concerned with the pathogenesis of ADC need more research.

OBJECTIVE: To study the bioequivalence of tegaserod maleate dispersible tablets in healthy volunteers.METHODS: A single oral dose of 6mg test or reference preparations of tegaserod maleate was given to 22 healthy volunteers in a randomized crossover study.The plasma concentrations of tegaserod were determined by LC/MS/MS assay.RESULTS: The main pharmacokinetic parameters of test and reference products were as follows: tmax(0.86? 0.22) and(1. 01? 0.24) h;Cmax(2.21? 0.69) and(2.05? 0.64) ng? mL1;AUC0～ 17(6.35? 2.48) and(6.47? 1.99) ng? h? mL-1,AUC0～ ∞(6.69? 2.59) and(6.70? 2.03) ng? h? mL-1,respectively.The relative bioavailability of test to reference preparation was(98.2? 22.1) %.CONCLUSION: The reference preparation and the test preparation are bioequivalent.

[ABSTRACT]AIM:Toexploretheroleofkisspeptin/GPR54signalingpathwayinthepathogenesisofprecocious puberty based on female precocious puberty rat model induced by the single dose of danazol .METHODS:Female SD rats aged 3 d were randomly divided into normal group , vehicle group and model group .On the 5th day, the model rats were given a single subcutaneous injection of danazol with ethanol and ethylene glycol mixture .All rats were executed on 15 d, 25 d, 30 d, 35 d and 40 d, and the samples were collected to observe the sexual organ development .The levels of E2 , FSH and LH in peripheral blood were measured by ELISA .The Kiss-1 mRNA expression of Kiss-1, GPR54 and GnRH in hypothalamus was detected by real-time PCR.The kisspeptin expression in rat hypothalamus was observed by immunofluo-rescence .RESULTS:The time for puberty onset and sexual maturation in the model rats was significantly earlier than that in normal group and vehicle group .On days 25 and 30, the levels of peripheral sex hormones and uterine coefficients in model group were significantly higher than those in normal group and vehicle group .On days 25 and 30, the ovarian mor-phological development in the model rats was significantly earlier than that in normal group .On day 25, the mRNA expres-sion of hypothalamic Kiss-1 and GnRH, and kisspeptin expression of hypothalamic arcuate nucleus in the model rats signifi -cantly increased compared with normal group and vehicle group .On day 30, kisspeptin expression of hypothalamic arcuate nucleus in the model rats decreased compared with normal group and vehicle group .On day 35, the mRNA expression of Kiss-1 and GnRH in the model rats decreased compared with normal group and vehicle group .The mRNA expression of GPR54 had no obvious difference among all groups .CONCLUSION:The Kiss-1 mRNA and kisspeptin expression in the model rats with precocious puberty is significantly increased in the hypothalamus during onset of puberty , suggesting that kisspeptin is an initiating factor for precocious puberty .Kisspeptin/GPR54 signaling pathway may play an important role in the occurrence of precocious puberty .