Objective To investigate the application of offline solid-phase extraction-high performance liquid chromatography-tandem mass spectrometry for detecting four synthetic cannabinoids(5F-ADB,5F-MDMB-PICA,4F-MDMB-BUTINACA,and MDMB-4en-PINACA)and their marker metabolites in urban wastewater.Methods Samples were pre-treated using an Oasis PRiME HLB column(60 mg,3CC)and analyzed by ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry.The mobile phases consisted of 0.02%formic acid-2 mmol/L ammonium formate aqueous solution and acetonitrile solution,with a WATERS ACQUITY UPLCHSS T3 column.Analysis was conducted in positive ionization mode of the ESI ion source,combining multiple reaction monitoring(MRM),information-dependent acquisition(IDA),and enhanced product ion(EPI)scanning modes for qualitative and quantitative analysis of the eight target compounds.Results Good linearity was observed for 4F-MDMB-BUTINACA-M,5F-ADB,5F-ADB-M,and 5F-MDMB-PICA in the concentration range of 1～250 ng/L;for MDMB-4en-PINACA in the range of 5～250 ng/L;and for 4F-MDMB-BUTINACA,5F-MDMB-PICA-M,and 4F-MDMB-BUTINACA-M in the range of 1～500 ng/L.The recovery rates of samples spiked with different concentrations of the eight target compounds ranged from 87.68%to 104.68%,with matrix effects between 88.61%and 112.78%.Both intra-day and inter-day precision were less than 5%.Conclusion The established method demonstrates good accuracy and reproducibility,making it suitable for qualitative and quantitative detection of four synthetic cannabinoids and their metabolites in urban wastewater.

Objective To investigate the application of offline solid-phase extraction-high performance liquid chromatography-tandem mass spectrometry for detecting four synthetic cannabinoids(5F-ADB,5F-MDMB-PICA,4F-MDMB-BUTINACA,and MDMB-4en-PINACA)and their marker metabolites in urban wastewater.Methods Samples were pre-treated using an Oasis PRiME HLB column(60 mg,3CC)and analyzed by ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry.The mobile phases consisted of 0.02%formic acid-2 mmol/L ammonium formate aqueous solution and acetonitrile solution,with a WATERS ACQUITY UPLCHSS T3 column.Analysis was conducted in positive ionization mode of the ESI ion source,combining multiple reaction monitoring(MRM),information-dependent acquisition(IDA),and enhanced product ion(EPI)scanning modes for qualitative and quantitative analysis of the eight target compounds.Results Good linearity was observed for 4F-MDMB-BUTINACA-M,5F-ADB,5F-ADB-M,and 5F-MDMB-PICA in the concentration range of 1～250 ng/L;for MDMB-4en-PINACA in the range of 5～250 ng/L;and for 4F-MDMB-BUTINACA,5F-MDMB-PICA-M,and 4F-MDMB-BUTINACA-M in the range of 1～500 ng/L.The recovery rates of samples spiked with different concentrations of the eight target compounds ranged from 87.68%to 104.68%,with matrix effects between 88.61%and 112.78%.Both intra-day and inter-day precision were less than 5%.Conclusion The established method demonstrates good accuracy and reproducibility,making it suitable for qualitative and quantitative detection of four synthetic cannabinoids and their metabolites in urban wastewater.

Objective To investigate the current status of off-label drug use(OLDU)management in tertiary hospitals of Guizhou province and to provide baseline evidence for developing a unified administration regulation for OLDU in Guizhou province.Methods In line with the relevant policies and regulations,a questionnaire including basic information about the person filling out the form,basic information about the hospitals,and information about OLDU was developed.The questionnaire was sent to 84 tertiary hospitals in Guizhou province through the Wenjuanxing.Results A total of 84 questionnaires were distributed and recovered,with a response rate of 100.00%.Of the 84 hospitals,77 had OLDU,of which 68(88.31%)had established a management system for OLDU.Among the 77 hospitals with OLDU,65(84.42%),42(54.55%),58(75.32%),36(46.75%),15(19.48%),and 21(27.27%)hospitals respectively,required approval from the Committee on Drug Administration and Pharmacotherapy before OLDU,restricted the qualifications of doctors prescribing OLDU,required informed consent from patients or their families before OLDU,recorded the matters and reasons in the medical records of patients treated with OLDU,followed up patients in their files and evaluated the reasonableness of the OLDU,and carried out special reviews for OLDU.Only 30(38.96%)hospitals have set up a catalogue of OLDUs,and 58(75.32%)hospitals have urgent needs to set up a unified provincial catalogue of OLDUs.Conclusion The pharmacy administration level of OLDU in tertiary hospitals of Guizhou province is relatively low,so there is an urgent need to establish a unified OLDU management system and medication catalog.

Objective To analyze the heat-clearing and anti-inflammatory mechanism of Xiaoyan Tuire Granules by network pharmacology,and to determine the 8 main active components of Xiaoyan Tuire Granules by ultra-high performance liquid chromatography-mass spectrometry(UPLC-MS/MS).Methods SwissTargetPrediction database was used to screen the target of components absorbed in the blood of Xiaoyan Tuire Granules.The main target of disease was obtained by CTD database,and the protein-protein interaction(PPI)was analyzed by String platform.GO and KEGG enrichment analysis were conducted using the DAVID database,followed by the construction of the components-targets-pathways network using Cytoscape software.Finally,the molecular docking verification of the key compound-target was conducted.The main active components in Xiaoyan Tuire Granules,including indirubin,isoliquiritigenin,liquiritigenin,glycyrrhizinic acid,liquiritin,esculetin,caffeic acid and chlorogenic acid,were determined by UPLC-MS/MS method.Analysis was performed on a WATERS ACQUITY UPLC? BEH C18 column(2.1 mm×100 mm,1.7 μm)with gradient elution of 0.1%formate in acetonitrile(A)-0.1%formate-5 mmol·L-1 ammonium formate(B),and the determination was carried out in multiple reaction monitoring(MRM)mode.Results Sixteen potential active components,such as indirubin,esculetin,and caffeic acid were identified by network pharmacology and molecular docking,and 10 core targets including transcription factor AP-1(JUN),adhesive connexin β1(CTNNB1)and cysteine aspartic protease-3(CASP3)were predicted.The pathway enrichment analysis revealed that heat-clearing and anti-inflammatory effects of Xiaoyan Tuire Granules were mainly related to signaling pathways such as interleukin-17(IL-17)and hypoxia-induced cause-1(HIF-1).Molecular docking experiments showed that its main active components docked well with core targets.The results of content determination exhibited that all components had good linear relationship within certain concentration range(r＞0.999),good precision,repeatability,and stability.The contents of 8 components in 16 batches of samples were 0.94-3.41,0.99-5.61,0.80-5.84,85.48-141.11,4.30-10.09,152.35-271.80,11.31-26.94,1.99-5.58 μg·g-1,respectively.The contents of indirubin,isoliquiritigenin,liquiritigenin,liquiritin,and chlorogenic acid in Xiaoyan Tuire Granules from two manufacturers were significantly different.Conclusion This study preliminarily revealed the mechanism of Xiaoyan Tuire Granules,which exerted heat-clearing and anti-inflammatory effects through multiple components,targets and pathways.A method for the determination of multiple components in Xiaoyan Tuire Granules was established.This study may provide a reference for its pharmacological research and quality control.

We investigated correlation between the level of miR-16 expression and the severity of Staphylococcus aureus sepsis,and further explored its potentially clinical significance.Blood samples were collected from 32 patients,including each 8 cases of septic shock,severe sepsis and general sepsis,as well as 8 cases of healthy volunteers.Blood samples from 24 cases of healthy subjects with different ages were measured,and additionally 8 cases of blood samples from gram negative bacteria sepsis were also determined in current study as a control.Trizol solution for the whole blood lysis was added into blood samples,and followed by the extraction of microRNA.The expression levels of miR-16 in different groups were measured by fluorescence quantitative PCR,in which 2-Delta Ct method was used.SPSS software (version 13.0) was used to analyze the statistical differences between the groups,and further analyze the correlation between miR-16 value and the corresponding CRP and PCT values.Results showed that the expression level of miR-16 was negatively correlated with the severity of Staphylococcus aureus sepsis.There were statistically significant differences in experimental groups when compared with the control (P＜0.001),and there was also a statistically significant difference between each experimental group (P＜0.01).We found that the expression level of miR-16 was negatively correlated with CRP and PCT,the correlation coefficients were-0.561 and-0.769 respectively,and trend analysis showed that there was a significantly negative correlation.A significantly negative correlation was found between the miR-16 expression level and severity of sepsis,suggesting that miR-16 may serve as a biomarker for the severity of Staphylococcus aureus sepsis.

OBJECTIVE:To discuss the barriers to entry of pharmaceutical industry of our country into international market.METHODS:Directed by the theory of the barriers to entry of the industry organization theory,the barriers to entry into the international pharmaceutical industry was ordered by using the methods of the excess profit,the enterprise numbers,and the proportion of enterprise scale.RESULTS:The barriers to entry into the international chemical pharmaceutical industry and the medical instrument industry are the highest in the sequence of pharmaceutical industry.CONCLUSION:At the time that the industry of our country is reforming,we should regulate and direct the pharmaceutical industry right by using the theory of the industry organization.