AIM: To develop a sensitive and rapid determination method of dopamine(DA) and its metabolites 3,4-dihydroxyphenylacetic acid(DOPAC) and homovanillic acid(HVA) in rat cerebral microdialysates.METHODS: Microdialysis probes were placed into the right stratums of Wistar rat brains and perfused with Ringer's solution at a rate of(1.5)(?l?min~(-1)).A reverse phase HPLC with electrochemical detection (ECD) were used to assay DA,DOPAC and HVA after the cerebral microdialysates were collected every 20 minutes from awake,freely moving rats.In order to know the reliability of this method,selectivity,linear range,precision and accuracy were tested and the contents of DA,DOPAC and HVA in rat microdialysates were determined.RESULTS:The standard curve were in good linear at the range of(12.5) to 250(?g?L~(-1)).The recovery rates of DOPAC,DA and HVA at the concentration of(0.05),(0.13),(0.25)(?g?L~(-1)) were(98.33)%,(102.67)%,(92.33)% respectively.Their with-in day RSD were(3.3)%,(3.4)%,(2.5)% and between-day RSD(4.2)%,(2.3)%,(5.6)% respectively.The contents of DOPAC,DA and HVA in rat microdialysates were(1.79)?(0.07),(0.45)?(0.02),(1.67)?(0.05)(?g?ml~(-1)) (n=6),respectively.CONCLUSION: The simple,accurate and stable method can be applied to the study of the basic researches of diseases related to DA by cerebral microdialysis in rat.

Aim To establish the model of oxidative damage in brain of Parkinsons disease(PD)rats induced by levodopa(L-DOPA)with microdialysis technique.Methods PD model rats were induced by intracerebral injection of 6-hydroxyl dopamine(6-OHDA)and were perfused in brain with L-DOPA by using microdialysis technique.Salicylic acid can capture hydroxyl radicals in brain,then yield 2,3-dihydroxy benzyl acid(2,3-DHBA)and 2,5-dihydroxy benzyl acid(2,5-DHBA).Extracelluler dopamine(DA)and its metabolites,2,3-DHBA and 2,5-DHBA in striatum of rats were measured by HPLC-ED before and after L-DOPA treatment.Results Both 2,3-DHBA and 2,5-DHBA in model group were significantly higher than those in control group at 6 and 7 time points respectively(P

OBJECTIVE: To establish a technical process for the separation and purification of total flavones from Licorice. METHODS: The static absorption capacity of macroreticular adsorptive resins D101、Hz-806、AB-83 for total flavones from licorice were compared. The macroreticular adsorptive resin columns on the Licorice extractives were eluted respectively with different concentrations of ethanol, then the content, the weight of residue and purity coefficient of flavones from Licorice in the eluant were detected. RESULTS: The optimal technological conditions were found in AB-8 as follows: flow rate=3ml/min, sample concentration=1.5 mg/ml, pH=5 and 80% ethanol was used as eluting agent. CONCLUSIONS: AB-8 macroreticular adsorptive resin can effectively separate and purify total flavones from licorice, the purity coefficient thus obtained being over 50%, which meets the requirement of the study of effective components of herbal medicine.

Background:Nocturnal gastroesophageal reflux (nGER)is associated with severe complication of gastroesophageal reflux disease (GERD),such as esophagitis,esophageal stricture and Barrett's esophagus,and has certain effect on quality of life. Aims:To study the characteristics of nGER and its influencing factor in patients with GERD. Methods:GERD patients with typical reflux symptoms (heartburn or/ and regurgitation)and nGER confirmed by MII-pH monitoring were included. Effects of gender,age,BMI,DBI on nGER were analyzed. Results:In 130 patients with GERD,97 (74. 6%)had nGER. Of the 97 patients with nGER,only 18 (18. 6%)patients complained nocturnal heartburn or/ and regurgitation. During nocturnal period,female and elderly GERD patients had delayed bolus clearance time. Percentage of time with pH < 4 and acid reflux of GERD patients with BMI≥25 kg/ m2 were significantly higher than patients with normal BMI. Nocturnal acid reflux was much lower in patients with DBI≥2. 5 hours than patients with DBI < 2. 5 hours. The weakly acidic reflux could significantly decrease along with the getting longer of DBI. Conclusions:nGER is prevalent in GERD patients,and weakly acidic reflux is the leading type,however,only a small part of patients having nocturnal reflux symptom. The female and elderly GERD patients have delayed bolus clearance time during nocturnal period. BMI≥25 kg/m2 is associated with nGER. DBI≥2. 5 hours could significantly reduce acid reflux during nocturnal period. DBI should be as long as possible for reducing weakly acidic reflux.

Background:Functional dyspepsia (FD)with anxiety and gastric hypersensitivity is still one of the therapeutic difficulties in clinic. Gastrodin (Gas)may have dual effects of modulating gastric sensitivity and anxiety. Aims:To investigate the effect of Gas on gastric sensitivity and anxiety-like behavior in FD with anxiety-like gastric hypersensitivity in rats. Methods:Forty rats were randomly divided into control group,model group,buspirone group,low-dose Gas group and high-dose Gas group. Maternal separation,acute gastric irritation and restraint stress were sequentially performed to induce FD model with anxiety-like gastric hypersensitivity. At the 8th week,rats in control group and model group were intraperitoneally injected with 0. 9% NaCl solution 2. 0 mL/ kg,rats in buspirone group were given buspirone 3. 125 mg/kg,and rats in low- and high-dose Gas groups were given 62. 5,125. 0 mg/ kg Gas,respectively. The course was 7 days. Then elevated plus maze (EPM),open field test,abdominal withdrawal reflex (AWR)and electromyography (EMG) were performed. Results:Compared with control group,EPM test showed that proportions of open arms entries and duration were significantly decreased (P < 0. 01);open field test showed that virtual central grids duration (P < 0. 05),number of virtual grids climbed and times of lifting were significantly decreased (P < 0. 01);when gastric balloon dilatation pressure was equal or greater than 40 mm Hg,AWR score,area under ROC curve (AUC)of EMG was significantly increased in model group (P < 0. 05). Compared with model group,above-mentioned indices in low- and high-dose Gas groups were significantly ameliorated (P < 0. 05). Conclusions:Gas could influence the gastric sensitivity and anxiety-like behavior of the brain-stomach axis regulated anxiety-like gastric hypersensitivity in FD rat model.

Objective To assess the efficacy and safety of 100 mg or 200 mg yimitasvir phosphate combined with sofosbuvir in patients with non-cirrhotic chronic hepatitis C virus ( HCV) genotype 1 infection who were treatment-na?ve or had a virologic failure to prior interferon-based treatment.Methods A multicenter, randomized, open-label, phase 2 clinical trial was conducted.The patients were randomly assigned to yimitasvir phosphate 100 mg+sofosbuvir 400 mg group (Group 100 mg) and yimitasvir phosphate 200 mg+sofosbuvir 400 mg group ( Group 200 mg) in a 1∶1 ratio with the stratified factors of " treatment-naive" or"treatment-experienced" for 12 weeks and followed up for 24 weeks after the end of treatment.During the clinical trial, HCV RNA was tested in all patients.Resistance of virus in patients who didn′t achieved sustained virological response (SVR) was monitored.Safety and tolerability were assessed by monitoring adverse events , physical examination , laboratory examination, electrocardiogram, and vital signs during the study.The primary end point was SVR12 after the end of therapy.Descriptive statistics were used for categorical variables and eight descriptive statistics were used for continuous variables.Descriptive statistics were used and summarized according to HCV genotypes and treatment groups.Safety data were presented using descriptive statistics and summarized according to treatment groups.Results A total of 174 subjects were screened from July 31, 2017 to September 26, 2018.One hundred and twenty-nine patients were successfully enrolled and received treatment , and 127 completed the study.There were 64 patients and 65 patients assigned to Group 100 mg and Group 200 mg, respectively.Among the 129 patients who underwent randomization and were treated , 18.6% were treatment-experienced and: 100%were HCV genotype 1b infection.The total SVR rate was 98.4%(127／129), with 98.4%(63／64, 95%confidence interval [CI]: 91.60%-99.96%) in the Group 100 mg, and 98.50%(64／65, 95%CI: 91.72%-99.96%) in the Group 200 mg.There was no significant difference between the two groups (χ2 ＝0.000 2, P＝0.989 2).The SVR rates in treatment-naive group and treatment-experienced group were 98.10%(95%CI: 93.29%-99.77%) and 100.00%(24／24, 95%CI: 85.75%-100.00%), respectively.Virological failure during treatment ( including breakthrough , rebound and poor efficacy) and relapse after treatment did not occur during the trial.By Sanger sequencing , 11.6%(15／129) patients had baseline NS5A Y93H／Y or Y93H resistance-associated substitutions ( RAS), 1.6%( 2／129) patients had baseline NS5A L31M RAS.No mutation was observed in NS5B S282 at baseline.There was no S282 mutation in HCV NS5B.A total of 100 (77.5%) subjects had adverse events.No adverse events ≥Grade 3 or severe adverse events related to the study treatment.No patient prematurely discontinued study treatment owing to an adverse event.No life-threatening adverse event was reported.Conclusion Twelve weeks of yimitasvir phosphate 100 mg or 200 mg combined with sofosbuvir 400 mg daily is a highly effective and safe regimen for patients without cirrhosis with HCV genotype 1b infection who had not been treated previously or had a virologic failure to prior interferon-based treatment.

Objective To investigate the efficacy and safety of the 12-week regimen with sofosbuvir and coblopasvir hydrochloride in the treatment of chronic hepatitis C (CHC) in northwest China. Methods This study enrolled 101 patients with CHC of any genotype who received sofosbuvir (400 mg) combined with coblopasvir hydrochloride (60 mg) for 12 weeks in The First Affiliated Hospital of Air Force Medical University, The Second Affiliated Hospital of Air Force Medical University, The Second Affiliated Hospital of Xi'an Jiaotong University, and Baoji Central Hospital from July 1 to December 31, 2021, among whom 13 had liver cirrhosis and 88 did not have live cirrhosis. Other antiviral drugs such as ribavirin were not added regardless of the presence or absence of liver cirrhosis or the genotype of CHC. Related clinical data ere extracted, including HCV RNA quantification and liver biochemical parameters at baseline, at week 12 of treatment, and at 12 weeks after drug withdrawal. The primary endpoints were sustained virologic response at 12 weeks after the end of treatment (SVR12) and safety at week 12 of treatment, and the secondary endpoint was the effect of the 12-week treatment on liver biochemical parameters. The non-normally distributed continuous data were expressed as M ( P 25 - P 75 ), and the Mann-Whitney U test was used for comparison between groups. Results A total of 101 patients were included in the analysis, among whom there were 55 male patients (54.5%) and 46 female patients, and the median age was 53 years. Among these patients, 12.8% had liver cirrhosis, 1.0% had liver cancer, 3.0% were treatment-experienced patients, and 3.0% had type 2 diabetes. As for genotype distribution, 8% had CHC genotype 1, 60% had CHC genotype 2, 19% had CHC genotype 3, and 6% had CHC genotype 6, and genotype was not tested for 7% of the patients. After 12 weeks of treatment, all 101 patients had a HCV RNA level of below the lower limit of detection and an SVR12 rate of 100%, with a significant reduction in the serum level of alanine aminotransferase (ALT) from baseline to week 12 of treatment ( P < 0.05). Among these patients, 22.7% had concomitant medications such as atorvastatin calcium, aspirin, metformin, nifedipine, bicyclol, and compound glycyrrhizin. The incidence rate of adverse events was 16.8%, and fatigue (12.9%) was the most common adverse event. Conclusion The 12-week treatment with sofosbuvir and coblopasvir hydrochloride can obtain high SVR12 in CHC patients in northwest China and has good antiviral safety, with a significant improvement in abnormal serum ALT at week 12 of treatment.