K21. The mean t1/2(?) was (2.7?0.4) h, Vd was about 11.18 L?kg-1.The C-T profile conformed to two compartment open model. The plasma Dau concentration-time curves showed a double-peak phenomenon in all dosages of all dogswhen dauricine was given by intragastric was.The tpeak(1) was (0.8?0.6) ～(1.2?0.5) h,tpeak(2) was (5.2?3.2) ～(6.5?1.9)h,Cmax(2) 0.05) and the AUC was increased in proportion.The drug is eliminated non-linearly when the dosage is above 50 mg?kg-1, the parameters t1/2(el),CL, AUC/X0 shows great difference (P

Aim The relative bioavailability of domestic ibudilast sustained release capsules in healthy volunteers was observed.Methods A single oral dose of 20 mg of imported and domestic ibudilast sustained release capsules and 10 mg of ibudilast raw material was separately given to 12 healthy volunteers in a randomized crossover study. Ibudilast concentration in plasma was determined by HPLC method.Results The Cmax were (54.9?9.7),(60.7?9.1) and (62.2?11.5) ?g?L-1; the tmax were (3.8?0.8),(3.9?0.8) and (1.8?0.3) h;the t1/2(ke) were (1.5?1.4),(12.1?1.0) and (3.5?0.5) h,and the AUC(0～t) were (618.1?57.7),(588.1?66.6) and (233.0?46.4) ?g?h?L-1 in imported capsule group, domestic capsule group and raw material group respectively. The relative bioavailability of domestic sustained release capsules of ibudilast is (95.6?11.0)%. Conclusion The results of statistical analysis demonstrate that the imported and domestic sustained capsules have significant character of significantly sustained release and are bioequivalent.

OBJECTIVETo observe the effect of calorie restriction on the high fat diet rats mRNA expressions of liver forkhead box O1(FoxO1), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G-6-P) and to explore the possible mechanisms.

METHODS24 normal 6-week-old male Wistar rats were randomly divided into three groups: normal chow group (NC, n = 7), high fat diet group (HF, n = 9) and calorie restriction group (CR, n = 8). They were fed for 12 weeks. At the end of the experiment, the rats were sacrificed and their fasting blood glucose (FBG), insulin (INS), triglycerides (TG), total cholesterol (TC) were measured. Their visceral fat (VF) and body weight (BW) were also measured and VF/BW was calculated. Gene expression was investigated by using semi-quantitative RT-PCR methods. Liver histology was studied with HE stained slides.

RESULTSCompared with the NC group, HF group rats developed visceral obesity which was accompanied by higher FBG, plasma INS, TG, and TC. The levels of FoxO1, PEPCK, and G-6-P increased by 18.9%, 33.8%, and 24.6%, respectively (P less than 0.01). Liver steatosis was observed with microscopy. The BW, VF FBG, INS, TG and TC of the CR group rats were lower in comparison to those of the HF group. The levels of FoxO1, PEPCK and G-6-P were lower by 26.6%, 35.0%, 34.3% (P less than 0.01). Meanwhile, liver steatosis was also milder.

CONCLUSIONCalorie restriction can inhibit the expressions of FoxO1, PEPCK and G-6-P, strengthen insulin signal conduction, suppress gluconeogenesis and thus regulate glycometabolism.

Animals ; Caloric Restriction ; Dietary Fats ; Forkhead Transcription Factors ; genetics ; Gene Expression Regulation ; Gluconeogenesis ; genetics ; Glucose-6-Phosphatase ; genetics ; Liver ; metabolism ; Male ; Nerve Tissue Proteins ; genetics ; Phosphoenolpyruvate Carboxykinase (ATP) ; genetics ; Rats ; Rats, Wistar

OBJECTIVETo compare brain lead accumulation and neurotoxicity induced by lead under drinking purified water and tap water on rat.

METHODSAll 104 male weaning SD rats were randomly divided into eight groups, matched-four pairs according to drinking water: tap water, purified water, tap water with lead 50 mg/L(lead acetate water-solution), purified water with lead 50 mg/L, tap water with lead 200 mg/L, purified water with lead 200 mg/L, tap water with lead 800 mg/L. All were fed with normal food and environmental cognitions kept consistent Morris water maze(including Place Navigation, Spatial Probe Test, Visible Platform Trial) was measured to test rat spatial learning at the 12 and 24 week. At the end of the experiment (28 week), rats were killed and the lead of brain and blood was measured by Graphite furnace atomic absorption spectrometric method; the NR1, NR2A, NR2B of NMDAR (N-methyl-D-aspartame receptor) in hippocampus were analyzed by RT-PCR.

RESULTSUnder the same lead exposure, no significant differences were observed in blood lead, however, brain lead level showed higher in drinking purified water group than that in tap water group. Expression of NR1, NR2A and NR2B in hippocampus of the rats drinking purified water was lower than those drinking tap water, especially at low lead exposure (50 mg/L) (P < 0.05). In the 24 week Morris water maze, place navigation test's escape latency showed significantly prolonged at the rats drinking purified water as compared with those drinking tap water on the pairs of 50 mg/L and 200 mg/L pb2+ groups (P < 0.05), and the differences occurred in early 1-2 days.

CONCLUSIONCompared with drinking tap water, drinking purified water might increase the accumulation of brain lead, lower NR1, NR2A, NR2B expression and delay the spatial learning and memory ability under chronic lead exposure in water.

Animals ; Drinking ; Intelligence ; drug effects ; Lead ; toxicity ; Male ; Maze Learning ; drug effects ; Memory ; drug effects ; N-Methylaspartate ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; drug effects

OBJECTIVETo evaluate the antagonism effects of green tea (GT) against microcystin LR (MC-LR) induced hepatotoxicity and nephrotoxicity in mice.

METHODSAll 40 male mice were randomly divided into four groups. Mice in group III and IV were pretreated with green tea for free drink at doses of 2 g/L and 12 g/L prior to MC-LR intoxication, for consecutively 18 days. The toxin treatment mice were administered continually intraperitoneal injections of MC-LR at a dose of 10 microg x kg(-1) x d(-1) bw from day 6th till sacrifice, continually 13 days. Mice were sacrificed and immediately subjected to necropsy, and the body weight, relative organ weight, serum biochemical parameters, antioxidant enzyme levels (SOD and GSH), lipid peroxidation products (MDA) and histopathology were systematically evaluated.

RESULTSMC-LR exposure led to increase the oxidative stress and organ injury was significantly observed through biochemical parameters and microscopic evaluation. However, high dose of GT pretreatment caused a significant elevation in serum GSH and SOD levels, and a decrease of serum MDA level as compared with MC-LR control. The mean values of GSH and SOD activities were separately 467.29 mg/L and 139.22 U/ml in group IV. Subsequently, GT pretreatment obviously diminished the serum ALT, AST and Cr activities. Those pathological damages in liver and kidney, were to a certain extent, lessened in GT pretreatment mice in correlation with the biochemical parameters.

CONCLUSIONGT might elevate antioxidant defense system, clean up free radicals, lessen oxidative damages and protect liver and kidney against MC-LR induced toxicity.

Animals ; Antioxidants ; pharmacology ; Chemical and Drug Induced Liver Injury ; Free Radicals ; metabolism ; Kidney Diseases ; chemically induced ; metabolism ; pathology ; Liver Diseases ; metabolism ; pathology ; Male ; Mice ; Mice, Inbred Strains ; Microcystins ; toxicity ; Oxidative Stress ; Tea

OBJECTIVETo study the heterogeneity of polymerase gene (P gene) within hepatitis B virus (HBV) genotypes based on a systematic analysis of 202 HBV P genes, providing some useful references for further studies on the relationship among HBV genotypes, P gene mutations, replication and nucleoside analogues drug-resistance.

METHODS202 HBV complete sequences containing P genes were obtained from GenBank and were analysed using computer softwares.

RESULTSThere were some genotype-related characteristics of HBV P genes. As reverse transcriptase domain was concerned, there were more amino acid divergences in genotype C and D compared with these in genotype A. There were also amino acid substitutions in the A-F conserved regions of the reverse transcriptase domain within and between HBV genotypes.

CONCLUSIONSThere are divergences of P genes and amino acids within and between HBV genotypes, which should be considered when amino acid changes are analyzed whether they are proposed to be drug-resistance mutations or the results from quasispecies-selected. Moreover, these divergences may affect the antiviral effect of nucleoside analogues on HBV with different genotypes.

Amino Acid Sequence ; DNA, Viral ; genetics ; DNA-Directed DNA Polymerase ; genetics ; Gene Products, pol ; genetics ; Genetic Heterogeneity ; Genotype ; Hepatitis B virus ; genetics ; physiology ; Humans ; Molecular Sequence Data ; Mutation ; Phylogeny

One-step green synthetic approach,with bovine serum albumin(BSA) as stabilizer and reductant, was developed for preparation of BSA hybrid fluorescence gold nanoclusters (AuNCs@BSA). The prepared AuNCs@BSA exhibited strong red fluorescence under UV light illumination. Upon excited at 360 nm, the fluorescence spectrum of AuNCs@ BSA exhibited maximum emission peak at 635 nm. AuNCs@ BSA was presented as uniform spherical morphology with diameter at (2.0 ±0.05) nm. The fluorescence of AuNCs@BSA could be quenched by Hg2+because of its metallophilic reaction. Based on the fluorescent spectrometry, a rapid detection system was developed for Hg2+detection in tap water. The AuNCs@BSA amount, pH and buffer system were optimized in this study. According to optimization results, ultrapure water (pH 5.0) was selected to dilute the AuNCs@BSA by 100 times, and 50 μL/well of AuNCs@BSA dilution was applied to detect mercury ion in tap water. Under the optimized conditions, the detection could be completed within 3 min,the fluorescence intensity of the system was linearly proportional to the concentration of mercury ion in the range of 0.5–900 μg/L with linear equations y=-26.76lgx+803.1(0.5-75 μg/L,R2=0.9951) and y=-0.27x+762.02 (75-900 μg/L,R2=0.9959). The limit of detection was 0.14 μg/L(3σ). The average recoveries in spiked tape water samples ranged from 86.8%-113.4% with relative standard deviation of less than 15%. The result implied that the developed method was able to apply to detect mercury ion rapidly, sensitively and conveniently.

Objective To investigate the application of thoracoscope combined with mechanical ventilation in elderly patients with chest trauma complicated by acute respiratory distress syndrome(ARDS).Methods Selected 49 elderly patients with chest trauma complicated by ARDS who were admitted into our hospital from Jan.2015 to Jun.2017 as the study objects.And divided these patients into the control group (n=25)and the observation group(n=24)upon the different treatment method.Patients of the control group underwent conventional thora-cotomy combined with mechanical ventilation,while patients of the control group underwent the microinvasive video -assisted thoracoscopic surgery(VATS)combined with mechanical ventilation.Post-operative incision size,duration of operation,intraoperative bleeding,severity of pain 5 days after surgery,drainage duration,patients with post-operative complication,and hospital stays after operation of all patients were e-valuated.Compared and analyzed the changes of pulmonary function before surgery and 1 week after surgery, as well as the VAS score and anxiety and depression of patients before and after surgery.Results The postoperative incision size,VAS score and operation time in the ob-servation group were significantly better those of the control group,and the difference was statistically significant(P<0.05).The postopera-tive complications of the observation group were significantly lower than that in the control group,and the difference was statistically signifi-cant(χ2=4.75,P<0.05).One week after treatment,the pulmonary function index of the observation group were obviously superior to the control group with statistically significant difference(P<0.05).And the improvement degree of anxiety and depression was better in the ob-servation group compared to the control group(P<0.05).Conclusion Compared to traditional thoracotomy,reasonable VATS will help to decrease the intra-operative bleeding,duration of operation,post-operative hospital stays,and number of complications after surgery.What is more,it can improve pulmonary function of elderly patients.In addition,it can relief the degree of anxiety and depression of patients after op-eration,which is better than ones accepting traditional thoracotomy.

Objective To explore the applied value of high-field intraoperative magnetic resonance imaging (iMRI) in multi-image fusion guided stereotactic brain biopsy.Methods Twenty-four patients with intracranial lesions were examined by conventional MRI and diffusion tensor imaging (DTI) with 1.5T iMRI system before operation in our hospital from June 2011 to April 2012.The digital image data and preoperative PET/CT image data were transferred into BrainLAB planning workstation and all kinds of images were automatically fused.We used the BrainLAB software to reconstruct the corticospinal tract (CST) and three-dimensional display the anatomic relationship of CST and brain lesions.Leksell surgical planning workstation was used to help to choose the best target site and the reasonable needle track.The 1.5T iMRI was used to effectively monitor the intracranial condition during brain biopsy procedure.Results Needle biopsies were successfully performed in all 24 patients and pathological diagnosis was explicitly obtained in 23 patients,leading to a diagnostic yield of 95.8％.No patient suffered from significant complications during or after surgery.Conclusions With the help of high-field iMRI,multi-image fusion guided stereotactic brain biopsy conduces to achieving the purpose of higher positive rate of biopsy and lower incidence of complications.The method with this design combining MRI-DTI fusion images with the frame-based stereotactic biopsy can play a significant role in intracranial lesions of deep functional areas.

OBJECTIVESInvestigate the clinical efficacy of cryotherapy ablation treatment for advanced hepatocellular carcinoma. analyse the predictive factors of cryotherapy ablation treatment.

METHODSThere were 190 cases of hepatitis B-related HCC patients with advanced HCC from 2005 to 2008 in our hospital. By using clinical cohort method, they included cryoablation group (147 cases) and control group (43 cases), The median survival time and time to disease progression were compared. Evaluate clinical significance of age, gender, location of portal vein tumor thrombus, HBeAg, tumor histological grade, Child-Pugh classification, end-stage liver disease (MELD) score, advanced liver cancer prediction system (ALCPS) score and the Eastern Cooperative Oncology Group performance status (ECOG PS) score for predicting the efficacy of cryoablation. Group rates were compared with the x2 test, survival analysis by using Kaplan-Meier method, survival rates were compared by Log-rank analysis; multiple factor survival analysis by using Cox regression model.

RESULTSMedian survival time of cryoablation group and Control group was 7.5 (4.2 to 14.6) months and 3.2 (1.2 to 8.6) months, median TTP was 3.5 (2.5 to 4.5) months and 1.5 (1.0 to 3.5 months), the differences were statistically significant ( P less than 0.05 ). Median OS and TTP of advanced HCC patients who had Well-differentiated tumor, Child-pugh A-class and low score of MELD score, ALCPS score, ECOG PS score were significantly longer than the poorly differentiate, Child-Pugh B-class and the high those scores ( P less than 0.05). ECOG PS ( P less than 0.05, 95% CI 1.074 to 2.143) and ALCPS (P less than 0.05, 95% CI 1.005 to 2.121) were independent predictors for OS of advanced HCC.

CONCLUSIONCryoablation treatment can prolong median OS and TTP of advanced HCC; ECOG PS and ALCPS are important predictors for survival time of advanced HCC.

Carcinoma, Hepatocellular ; surgery ; Cryosurgery ; Female ; Humans ; Liver Neoplasms ; surgery ; Male ; Middle Aged ; Prognosis ; Proportional Hazards Models ; Survival Rate ; Treatment Outcome