AIM: To establish an HPLC-MS method for simultaneously determining four effective components in Guilin Watermelon Frost(Mirabilitum Praeparatum,Rhizoma Coptidis,Radix Scutellariae,etc.). METHODS: The sample was extracted with methanol containing 20% chloroform under ultrasonication.The HPLC separation was performed on Zorbax SB C_(18)(3.0 mm?250 mm,5 ?m) column using water including 0.5% formic acid(A)-methanol(B) as mobile phase,with the gradient elution(0-2 min,60%B;2-5 min,60%→90%B;5 min to the end,90%B), at a flow rate of 0.40 mL/min.The compounds were analyzed by ESI-MS under ion monitoring mode(0-3 min,m/z 249;3-6 min,m/z 336;6-10 min,m/z 447;10-16 min,m/z 263). RESULTS: The linear ranges were 0.020-10.0 ?g/mL,0.010-40.0 ?g/mL,0.036-50.0 ?g/mL and 0.040-4.00 ?g/mL for matrine,berberine,baicalin and indirubin,with detection limits of 0.005,0.001,0.006 and 0.010 ?g/mL,respectively.The average recoveries ranged from 96% to 101% with all relative standard deviations less than 3%.CONCLUSION: (The method is rapid,accurate and suitable for the quality control of the four effective) components in Guilin Watermelon Frost.

Objective To investigate the changes of serum 8-hydroxy-2'-deoxyguanosine(8-OHDG) in Kawasaki disease (KD) children and to explore the importance of 8-OHDG in predicting the severity of coronary artery lesions in Kawasaki Disease.Methods The serum 8-OHDG was measured in KD patients group (n =60),fever patients group (n =12) and health control group (n =12) by ELISA method.Among the KD patients,30 KD patients were in acute stage (10 cases had coronary artery lesions,20 coronary were normal) and 30 patients were in recovery stage.The serum 8-OHDG and brain natriuretic peptide (BNP) were also compared between patients with coronary artery lesions (CALs) and patients with no coronary artery lesions NCALs).ROC curve analysis was used to test the 8-OHDG and BNP predictive values in KD with coronary artery lesions.Results The serum level of 8-OHDG was higher in acute KD patients than recovery KD patients,fever patients and healthy children (P ＜ 0.05) The serum 8-OHDG was higer in CALs patients than the NCALs patients (P ＜ 0.05).The serum BNP was higer in CALs patients than the NCALs patients (P ＜ 0.01).Analysis of the ROC curve showed that serum 8-OHDG had a positive predictive value of 64.3％ and a negative predictive value of 93.8％for distinguishing KD with CALs from KD NCALs when cutoff value was 57.02pg/ml.The area under the curve was 0.820.The serum BNP had a a positive predictive value of 47.6％ and a negative predictive value of 100％ for distinguishing KD with CALs from KD NCALs when cutoff value was 815pg/ml.The area under the curve was 0.745.Conclusion The serum 8-OHDG may have better predictive value than BNP in diagnose KD children with coronary artery lesions.

BACKGROUND: Dopamine is closely associated with occurrence of epilepsy and transmission in central nerval system, and its various functions are determined by specific receptors.OBJECTIVE: To establish temporal epilepsy model so as to probe into the influences of SCH23390, the antagonist of dopamine D1 receptors and haloperidol, the antagonist of dopamine D2 receptors injected in substantia nigra on temporal epileptic seizure induced by kainic acid and on electroencephalic activityDESIGN: Randomized controlled verified experiment.SETTING: Neurology Medicine Institute of Zhujiang Hospital Affiliated to Southern Medical University.MATERIALS: The experiment was performed in General Military Neurology Medicine Institute of Zhujiang Hospital Affiliated to First Military University of Chinese PLA from August to December 2004, in which, 30SD adult male rats were employed, massed varied from 250 to 300 g.METHODS: ① 30 rats were randomized into physiological saline (control) group (6 rats), kainic acid (KA) group (6 rats) and experimental group (18 rats). The experimental group was divided into 3 subgroups, named the antagonist of dopamine D1 receptors, SCH23390 + kainic acid group (D1 +KA group), the antagonist of dopamine D2 receptors,haloperidol + kainic acid group (D2+KA group) and physiological saline + kainic acid group (PS + KA group), 6 rats in each. In the control, physi ological saline 2 μL was injected in the right cerebral ventricle unilaterally. In KA group, kainic acid 2 μL was injected in the right ventricle. In each of experimental group, SCH23390, the antagonist of dopamine D1 re ceptors, haloperidol, the antagonist of dopamine D2 receptors and physio logical saline 1 μL for each was injected in substantia nigra on the right side successively and simultaneously, kainic acid 2 μL was injected in the right ventricle. ② Observed items: alters of EEG on the 0.5th 1st, 2nd, 6th and 24th hours after medication in each experimental group (compared with EEG of non-epileptic behavior, appearance of sharp wave, spike wave,sharp (spike) slow comprehensive wave and multi-spike slow wave determines epileptic activity) and changes in animal behaviors (0 grade: normal; Ⅰ grade: wet dog-like trembling, paroxysmal facial spasm, like winking,beard moving, rhythmic chawing; Ⅱ grade: rhythmic nodding; Ⅲ grade:paroxysmal spasm of anterior limbs; Ⅳ grade: paroxysmal spasm of bilateral anterior limbs when standing; Ⅴ grade: falling down, loss of balance and convulsion of four limbs). Cerebral hippocampal neural cell apoptosis was observed and the rats were sacrificed on the 5' day of medication. Cerebral hippocampal section was prepared and determined after in situ end labeling staining.MAIN OUTCOME MEAUSRES: ① Changes in behavior in rats before and after epilepsy and electroencephalogram (EEG) alters. ② Results of cerebra hippocampal neural cell apoptosis.RESULTS: Thirty rats entered result analysis. ① Epilepsy seizure: In the control group, there was no epilepsy attacked. In KA group, all of rats ap pear seizure, which attacked 10 minutes after KA injected in brain ventricle, reached the peak in 1 hour and stopped in 3 to 6 hours. ② EEG record: In the control group, there was not epileptic activity manifestations,like sharp wave, spike wave, spike slow comprehensive wave, etc. In KA group, epileptic wave presented in 10 minutes after injection, the seizure developed to the peak in about 1 hour, the wave amplitude was decreased in 3 to 6 hours, presenting paroxysmal slow and spike slow waves and no epileptic wave appeared after 12 hours. ③ Neuronal apoptosis: In the control group, few neural cell apoptosis was visible in hippocampus after injection.In KA group, neural cell apoptosis was visible obviously in hippocampus in 5 days after injection (P =0.00). With SCH23390, the antagonist of dopamine D1 receptors, hippocampal cell apoptosis was not reduced remarkably (P ＞0.05) and with haloperidol, the antagonist of dopamine D2 receptors injected in substantia nigra, hippocampal cell apoptosis was aggravated (P =0.00).CONCLUSION: Injection of SCH23390, the antagonist of dopamine D1 receptors in substantia nigra cannot block kainic acid inducing epilepsy and epileptic electroencephalic activity is not weakened remarkably. Injection of haloperidol,the antagonist of dopamine D2 receptors enhances epileptic electroencephalic activity in kainic acid induced epilepsy and increases cell apoptosis remarkably in cerebral hippocampal CA3 area.It is to explain that it is dopamine D2 acceptor that is involved in regulation of temporal epilepsy in substantia nigra rather than D1 acceptor.

With the increasing cost of drug development and clinical trials, it is of great value to make full use of all kinds of data to improve the efficiency of drug development and to provide valid information for medication guidelines. Model-based meta-analysis (MBMA) combines mathematical models with meta-analysis to integrate information from multiple sources (preclinical and clinical data, etc.) and multiple dimensions (targets/mechanisms, pharmacokinetics/pharmacodynamics, diseases/indications, populations, regimens, biomarkers/efficacy/safety, etc.), which not only provides decision-making for all key points of drug development, but also provides effective information for rational drug use and cost-effectiveness analysis. The classical meta-analysis requires high homogeneity of the data, while MBMA can combine and analyze the heterogeneous data of different doses, different time courses, and different populations through modeling, so as to quantify the dose-effect relationship, time-effect relationship, and the relevant impact factors, and thus the efficacy or safety features at the level of dose, time and covariable that have not been involved in previous studies. Although the modeling and simulation methods of MBMA are similar to population pharmacokinetics/pharmacodynamics (Pop PK/PD), compared with Pop PK/PD, the advantage of MBMA is that it can make full use of literature data, which not only improves the strength of evidence, but also can answer the questions that have not been proved or can not be answered by a single study. At present, MBMA has become one of the important methods in the strategy of model-informed drug development (MIDD). This paper will focus on the application value, data analysis plan, data acquisition and processing, data analysis and reporting of MBMA, in order to provide reference for the application of MBMA in drug development and clinical practice.