Objective To study the analgesic sites and mechanism of total alkaloids in Papaver nudicaule (TAPN). Methods The sites of analgesic action of TAPN were observed by adopting Formalin test and two different routes of intracerebroventricular (icv), intrathecal (ith) in mice and rats and comparing ED 50 of TAPN in writhing reaction in mice induced by acetic acid by ip and iv administration. Results TAPN significantly lowered pain score of the early and late phase of Formalin response and was more sensitive in the late phase. Inhibition of TAPN at the same dose by ip administration in writhing reaction in mice induced by acetic acid was stronger than that by iv. The ED 50 value of TAPN at any time by ip administration was lower than that by iv administration. By means of central microinjection, TAPN by icv administration induced remarkable analgesic effect in mice, but TAPN by ith administration had no significant analgesic effect. Conclusion The sites of analgesic action of TAPN are mainly at periphery. TAPN has also central analgesic effect, and the site may be at the level above the spinal cord.

BACKGROUND: Qinggong changchun dan (QGCCD) capsule has efficacy in profiting kidney-yang and bettering muscle or bone, it could treat debility, deficiency of energy, forgettery and tiredness and the ache of waist or knee in clinic.OBJECTIVE: To study the effect of QGCCD capsule on stress capability of mice with kidney-yang deficiency.DESIGN: Completely randomized controlled trial.SETTING: Institute of Traditional Chinese Medicine, Chengde Medical College (Key Laboratory of Research and Exploiture of Traditional Chinese Medicine in Hebei Province).MATERIALS: Totally 60 stirp Kunming mice, weighting 19-21 g, of either gender, of grade Ⅱ, were selected in this study.METHODS: The experiment was conducted in the Department of Pharmacology and Toxicology, Institute of Traditional Chinese Medicine of Chengde Medical College from February 2002 to December 2002. Totally 160 Kunming mice of either gender were randomly divided into three groups:Swimming endurance group (n=60), tolerance of hypoxia at normal pressure group (n=50) and single macrophage function group (n=50); and mice in each group were divided into 5 subgroups, including 0.25, 0.5,1.0 g/kg QGCCD groups, model control group and normal control group.Mice were fasted for 12 hours and injected with 25 mg/kg hydrocortisone for 7 successive days to establish yang-deficiency model. Various dosages of QGCCD were given with the same volume of 20 mL/kg for 7 successive days. Mice in model control group were treated with the same volume of saline. Forty minutes later, testes of swimming tolerance, tolerance time of anoxia and engulfment capability of macrophage were performed on mice [To take 20 μL blood in the eyepit vein plexus after the mice were injected 2 minutes and 10 minutes later respectively, and to count the charcoal particle expurgation index (K) of macrophage] to observe effect of various dosages of QGCCD on swimming tolerance, tolerance time of anoxia and engulfment capability of macrophage.RESULTS: Data of totally 160 mice was entered the final analysis without normal control group were longer than those of mice in model control group [(10.94±3.79), (13.68±5.62), (14.58±5.49), (16.12±2.35), (6.45±4.87) minutes;ia of mice in 0.25, 0.5, 1.0 g/kg QGCCD groups and normal control group were longer than those of mice in model control group [(19.45 ±4.63),(21.18±4.25), (22.58±5.21), (23.12±4.78), (12.35±4.89) minutes; t=1.566,macrophage and K index of mice in 0.25, 0.5, 1.0 g/kg QGCCD groups and normal control group were higher than those of mice in model control group (0.023 6±0.010 6, 0.029 1±0.0092, 0.030 8±0.008 6, 0.031 8±0.010 1, 0.012 5±0.008 1; t=2.63, 4.282, 4.898, 4.714, P ＜ 0.05-0.01).CONCLUSION: QGCCD can prolong the swimming time of mice obviously, prolong tolerance time of anoxia according to dosage dependence,increase engulfment capability of macrophags, and strengthen stress capability of mice with kidney-yang deficiency.

Objective To study the relationship between analgesic effect of total alkaloids in Papaver nudicaule(TAPN) and prostaglandins(PGs) with opium receptors.Methods The analgesic effect of TAPN was studied by hot-plate, writhing,electric-evoked methods of mice.The analgesic mechanisms of TAPN and PGs with opium receptors were studied by the writhing numbers induced by different substances(Ach,AA,MgSO_4),the PGE_2 level in celiac fluid in mice after treated by AA writhing test and the antagonistic experiment of Naloxone.Results The inhibitory effect of TAPN on the writhing induced by Ach and AA in mice was stronger than that induced by MgSO_4.TAPN could also lower the PGE_2 level in celiac fluid.In the antagonistic experiment of Naloxone,no antagonism to the analgesic effect of TAPN had been found by ip or icv Naloxone.Conclusion It may be the mainly peripheral analgesic mechanism that TAPN could lower the PGE_2 level in celiac fluid.Its central analgesic mechanisms are not related to opium receptors.

Objective To investigate the efficacy of the indocyanine green (ICG) clearance test (ICGR15) combined with the model for end-stage liver disease (MELD) for assessing the short-term prognosis of patients with liver failure.Methods Eighty patients with liver failure were analyzed retrospectively.ICGR15 and relevant clinical data within 24 hours of diagnosis were analyzed.Meanwhile,the MELD score and King's College Hospital (KCH) were evaluated.All findings were tested for correlation with 3-month mortality.Quantitative data were analyzed with analysis of variance and Student's t-test.Count data were analyzed with chi-square test.Correlation analysis was performed with Pearson's coefficient test.Results Among 80 patients with liver failure,39 patients survived and 41 died.The mortality rate of all patients was 51.2％.The serum total bilirubin,creainine concentrations,ICGR15,MELD scores and patient number in accordance with KCH criteria of surviving patients were (288.0±109.1) μmol/L,(63.3±24.4) μmol/L,(48.1±10.2)％,20.6±4.4,and 6 cases,respectively,which were lower than those in dead patients [(340.7 ± 108.2) μmol/L,(98.8 ± 59.1) μmol/L,(60.2 ± 10.6) ％,26.9 ± 7.1 and 19 cases,respectively] (P =0.033,P＝ 0.001,P＝ 0.000,P＝ 0.000 and P =0.003,respectively).There was no significant difference of ICGR15 among four types of liver failure.A positive correlation was observed between ICGR15 and MELD score (r=0.289,P=0.009).The ICGR15-MELD model was created by subjecting ICGR15 and MELD scores to Logistic regression analysis.The following ICGR15-MELD model,Logit (P) =0.105 × ICGR15 + 0.178 × MELD score-9.734,was constructed by Logistic regression analysis.The area under the receiver operating characteristic (ROC) curve was 0.860 and the cut offpoint of 0.3 had sensitivity of 85.40％ and specificity of 74.40％.The area under the curve of the ICGR15-MELD model was significantly higher than those of ICGR15 (0.791),MELD score (0.770) and KCH criteria (0.655).Conclusions ICGR15 and MELD scores perform better than the KCH criteria in predicting the prognosis of liver failure.The ICGR15-MELD model is superior to ICGR15,MELD score,and KCH in predicting the short term prognosis of patients with liver failure.

Objective:To evaluate the value of mechanical ventilation combined with ultrasound in evaluating the volume reactivity of patients with septic shock.Methods:A prospective study was performed, and 59 patients with septic shock who were admitted to the Emergency Intensive Care Unit of the First Affiliated Hospital of Xinjiang Medical University from October 2016 to February 2018 were included according to the established inclusion and exclusion criteria. First, end-expiratory block test (EEO) and end-inhalation block test (EIO) were performed, followed by volume expansion test (VE) (intravenous infusion of 250 mL saline for 10 min), with cardiac index (CI) change value after VE (ΔCI)≥15% for volume-responsive group (37 cases), ΔCI<15% for volume-free group (22 cases), Vigileo-FloTrac system was used to continuously monitor EEO, EIO, and VE before and after changes in hemodynamic parameters, such as central venous pressure (CVP), mean arterial pressure (MAP), stroke volume variation (SVV), CI, and improved inferior vena cava diameter (IVCD) and respiratory variability index (RVI). The values of predicted capacity reactivity such as changes in CVP, MAP, SVV, CI, and RVI before and after EIO were evaluated, and the relationship between EEO, EIO, and capacity reactivity was analyzed by ROC curve.Results:There was no significant difference between MAP and CI in the response group and non-response group after EEO, EIO and VE intervention ( P>0.05). EEO-ΔSVV, EEO-ΔRVI, EEO-ΔCVP, EIO-ΔSVV and EIO-ΔRVI were compared between the reaction group and the non-reaction group, and the difference was statistically significant ( P<0.05); In the correlation analysis, EEO-ΔRVI and EIO-ΔRVI were correlated with VE-ΔRVI ( r=0.695, P<0.01; r=-0.489, P<0.01); EEO-ΔCVP and VE-ΔCVP were correlated ( r=0.566, P<0.01); EEO-ΔSVV, EIO-ΔSVV are related to VE-ΔSVV ( r=0.842, P<0.01; r= -0.727, P<0.01), and the ROC curve showed ( AUCEEO-ΔSVV=0.890, 95% CI: 0.792-0.988), showed AUCEEO-ΔSVV> AUCEEO-ΔRVI> AUCEIO-ΔSVV> AUCEIO-ΔRVI> AUCEEO-ΔCVP. Conclusions:EEO and EIO combined with ultrasound have certain clinical value in the evaluation of volume responsiveness in patients with septic shock, and the evaluation value of SVV and RVI is superior to CVP, MAP, and CI.

Objective: To investigate the clinical effect and safety of long-acting pegylated interferon-α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 μg/week) in the treatment of HBeAg-positive chronic hepatitis B (CHB) patients, with standard-dose Peg-IFN-α-2a as positive control. Methods: This study was a multicenter, randomized, open-label, and positive-controlled phase III clinical trial. Eligible HBeAg-positive CHB patients were screened out and randomized to Peg-IFN-α-2b (Y shape, 40 kD) trial group and Peg-IFN-α-2a control group at a ratio of 2:1. The course of treatment was 48 weeks and the patients were followed up for 24 weeks after drug withdrawal. Plasma samples were collected at screening, baseline, and 12, 24, 36, 48, 60, and 72 weeks for centralized detection. COBAS® Ampliprep/COBAS® TaqMan® HBV Test was used to measure HBV DNA level by quantitative real-time PCR. Electrochemiluminescence immunoassay with Elecsys kit was used to measure HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe). Adverse events were recorded in detail. The primary outcome measure was HBeAg seroconversion rate after the 24-week follow-up, and non-inferiority was also tested. The difference in HBeAg seroconversion rate after treatment between the trial group and the control group and two-sided confidence interval (CI) were calculated, and non-inferiority was demonstrated if the lower limit of 95% CI was > -10%. The t-test, chi-square test, or rank sum test was used according to the types and features of data. Results: A total of 855 HBeAg-positive CHB patients were enrolled and 820 of them received treatment (538 in the trial group and 282 in the control group). The data of the full analysis set showed that HBeAg seroconversion rate at week 72 was 27.32% in the trial group and 22.70% in the control group with a rate difference of 4.63% (95% CI -1.54% to 10.80%, P = 0.1493). The data of the per-protocol set showed that HBeAg seroconversion rate at week 72 was 30.75% in the trial group and 27.14% in the control group with a rate difference of 3.61% (95% CI -3.87% to 11.09%, P = 0.3436). 95% CI met the non-inferiority criteria, and the trial group was non-inferior to the control group. The two groups had similar incidence rates of adverse events, serious adverse events, and common adverse events. Conclusion In Peg-IFN-α regimen for HBeAg-positive CHB patients, the new drug Peg-IFN-α-2b (Y shape, 40 kD) has comparable effect and safety to the control drug Peg-IFN-α-2a.