ABSTRACT
OBJECTIVE： To establish a method for the determination of piperitylmagnolol in the incubation system of liver microsomes， and to investigate the metabolic characteristics of it in different species of liver microsomes. METHODS： The piperitylmagnolol were respectively dissolved in NADPH activated liver microsome incubation systems of human， rat， mouse， monkey and dog， and then incubated in water at 37 ℃. The reaction was terminated with methanol at 0， 2， 5， 10， 15， 20， 30， 45 and 60 minutes of incubation， respectively. Using magnolol as internal standard， UPLC-MS/MS method was used to determine the concentration of piperitylmagnolol in the incubation system. The determination was performed on Acquity UPLCTM CSH C18 column with mobile phase consisted of 0.1％ formic acid-methanol （gradient elution） at the flow rate of 0.3 mL/min. The column temperature was set at 30 ℃， and the sample size was 2 μL. The ion source was electrospray ion source， and the positive ion scanning was carried out in the multiple reaction monitoring mode. The ion pairs used for quantitative analysis were m/z 401.2→331.1 （piperitylmagnolol） and m/z 265.1→247.0 （internal standard）， respectively. Using the concentration of piperitylmagnolol at 0 min of incubation as a reference， the residual percentage， metabolism half-life in vitro （t1/2） and intrinsic clearance （CLint） were calculated for different incubation systems. The metabolic pathway of piperitylmagnolol was studied by chemical inhibitor method. Under the above chromatographic conditions， the metabolites in vitro were preliminarily analyzed by first-order full scanning and positive ion detection. RESULTS： The linear range of piperitylmagnolol was 3.91-500.00 ng/mL. The limit of quantitation was 3.91 ng/mL. RSDs of intra-day and inter-day were less than 10％. The accuracy ranged 87.40％-103.75％. Matrix effect didn’t affect the determination of the substance to be measured. The piperitylmagnolol was metabolized significantly in human， rat， mouse and dog liver microsomes， but not in monkey liver microsomes. After incubating for 30 min， residual percentage of piperitylmagnolol kept stable in different species of liver microsomes. The t1/2 of piperitylmagnolol were 12.07， 17.68， 17.59， 216.56 and 61.88 min in human， rat， mouse， monkey and dog liver microsomes； CLint were 0.115， 0.078， 0.079， 0.006， 0.022 mL/（min·mg）， respectively. Inhibitory rates of CYP2A6， CYP2D6， CYP2C19， CYP3A4， CYP2C9， CYP2E1 and CYP1A2 to compound metabolism were 55.76％， 93.94％， 96.01％， 93.69％， 71.81％， 23.25％， 28.04％， respectively. Quasi-molecular ion peaks of the two main metabolites of piperitylmagnolol in human liver microsomes were m/z 441.2（[M+Na]+） and m/z 337.2（[M+H]+）， respectively. CONCLUSIONS： Established UPLC-MS/MS method is simple， rapid and specific， and can be used for the determination of piperitylmagnolol concentration in the incubation system of liver microsomes and pharmacokinetic study. The metabolic characteristics of the compound are different among liver microsomes of human， rat， mouse， monkey and dog. Its metabolism process may be associated with CYP2D6， CYP2C19， CYP3A4， CYP2C9， etc.
ABSTRACT
Objective To investigate the predictive value of early measurement of serum inflammatory mediators for infectious pancreatic necrosis secondary to severe acute pancreatitis (SAP).Methods A retrospective analysis was performed for the clinical data of 166 patients who were admitted to our hospital from January 2012 to January 2017.According to the presence or absence of secondary infectious pancreatic necrosis,the patients were divided into infection group with 58 patients and non-infection group with 108 patients.The serum levels of inflammatory factors were compared between the two groups.The receiver operating characteristic (ROC) curve was used for the analysis of indices with statistical significance.The independent samples t-test was used for comparison of continuous data between groups,and the chi -square test was used for comparison of categorical data between groups.Results Of all 166 SAP patients,58 experienced secondary infectious pancreatic necrosis,resulting in an incidence rate of 34.9％.Compared with the non-infection group,the infection group had significantly higher serum lipase,procalcitonin (PCT),C-reactive protein (CRP),and APACHE Ⅱ score (t =8.679,20.416,18.429,and 8.563,all P ＜0.05).The ROC curve analysis showed that serum lipase,PCT,CRP,and APACHE Ⅱ score had areas under the ROC curve of 0.647,0.877,0.823,and 0.655,respectively,with cut-off values of 612.5 U/L,7.5 ng/ml,226.5 mg/L,and 16.5 points,sensitivities of 68.5％,91.2％,86.8％,and 60.5％,and specificities of 59.3％,83.6％,80.1％,and 68.7％,respectively.Conclusion The abnormally elevated serum levels of CRP and PCT have a certain predictive value for infectious pancreatic necrosis secondary to SAP with convenient and fast operation,and therefore,it holds promise for clinical application.
ABSTRACT
Objective To understand the current situation about flexible position switch of non-licensed nurses in Chongqing, to discuss the cause of the flexible position switch, and to provide basic information for constructing scientific managerial measure. Methods Using the stratified clustering method to sample the nurses from 18 hospitals of different ranks in Chongqing and investigated them with self-designed questionnaire. Results Among the 1145 non- licensed nurses joining the investigation, 42.53%and 52.49% of them showed the will to switch their positions or occupations, 84.89% of them objected their children to occupy themselves with nursing service. 68.56% non-licensed nurses believed that flexible position switching had influence on themselves, while 74.50% of them believed that flexible position switching had impacts on hospitals. The main cause of the flexible position switching of non-licensed nurses included: feeling their work not beyond exceptions、 not enough respect in hospital 、lack of further development, and so on. Conclusions The high rate of will for flexible position switch cause great influences on the development of hospitals and non-licensed nurses themselves. Better treatment and raising respect should be given to them in order to stabilize nursing team.
ABSTRACT
This study sought to determine the impact of dental fluorosis severity on demineralization and remineralization of human fluorosed teeth in vitro. Surface enamel microhardness was measured on the enamel blocks before and after demineralization and after remineralization. The results showed that after demineralization, the sequence of % Surface microhardness demineralization (% SMHD) was TFI4 (18.92 +/- 1.31) < TFI3 (20.50 +/- 1.32) < TFI2 (25.08 +/- 1.69) < TFI1 (27.77 +/- 1.79) < TFI0 (30.70 +/- 1.35) (P < 0.05), and there was no statistically significant differences between TFI1 (27.77 +/- 1.79) and the normal group TFI0 (30.70 +/- 1.35). After remineralization, the sequence of % Surface microhardness remineralization (% SMHR) was TFI1 (55.17 +/- 1.23) > TFI0 (53.97 +/- 3.05) > TFI2 (49.17 +/- 1.81) > TFI3 (44.85 +/- 1.89) > TFI4 (36.51 +/- 2.95) (P < 0.05). Moderately fluorosed enamel showed a significatnt resistance to caries, but mildly fluorosed enamel could get better remineralization. These facts and figures deserve clinicians' attention.