最新刊期
卷 32 ， 期 8 ， 2021
- 摘要：OBJECTIVE：To evaluate the price and affordability of rare disease drugs in China and provide the suggestions for the improvement of rare disease drug affordability in order to provide reference for the relevant decision-making of government departments. METHODS ：According to the List of the First Batch of Rare Diseasesand Diagnosis and Treatment Guideline for Rare Diseases（2019 edition），rare disease drugs were selected. The median price ratio （MPR）was used to evaluate the drug price level ， and the ratio of the annual drug costs to the annual disposable income of urban or rural residents was used to evaluate the affordability，and the impact of price management policieson drug prices and affordability. RESULTS and CONCLUSIONS ：A total of 71 kinds of rare disease drugs were included ，and the median MPR of them was 0.83；among them ，the median MPR of the original drugs was 1.13，and the median MPR of the generic drugs was 0.37. The annual cost of 71 rare disease drugs was 0.001-178.43 times the average annual income of urban residents ，and 0.003-456.57 times the average annual income of rural residents. There were 21 and 28 drugs whose annual cost exceeded the annual income of urban and rural residents.After the implementation of national medical insurance negotiation or volume based procurement of 14 drugs，the median MPR of these drugs decreased from 1.71 to 0.46. For urban residents ，the number of unaffordable drugs had been reduced from 8 to 0；for rural residents，it had been reduced from 10 to 5. In summary ，the price level of orphan drugs in China was slightly lower than international reference price ，but the price level of original drugs was higher than the international reference price ，and the cost of some drugs far exceeded the residents ’ability to pay. It is suggested that the government should strengthen the price management of original drugs ，promote the substitution of high-quality generic drugs for original drugs ，and improve the payment system for high-value rare disease drugs.关键词：Rare disease drugs;Drug price;Median price ratio;Affordability
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发布时间：2022-06-21 - 摘要：OBJECTIVE：To provide technical met hods for marketing authorization holder （MAH）to effectively use the data of adverse drug reaction （ADR），actively monitor and control the production quality risk ，and carry out drug production risk management. METHODS ：Through establishing three-dimensional risk matrix and risk trend model ，the risk early warning system of MAH production line based on ADR report data is designed and developed ；the main functions of the system were applied and analyzed according to the actual ADR report data of a certain company. RESULTS ：MAH production line risk warning system was established preliminarily. The main framework included data source and and processing module ，model construction module （three-dimensional matrix model included possibility index ，severity index and sensitivity index ，risk trend model was set according to the principle of product production batch number preparation ），and result output & analysis module. Five major functional modules included system configuratio ，production line signal detection ，visual statistical early warning ，ADR report management and standard data management. The application and analysis of ADR report data of a certain company showed that the system could realize detection and warning of the company ’s production line risk ，which intuitively reflected its high-risk production lines ，varieties and batch numbers. It was consistent wit h the actual safety sit uation of the company ’s varieties. CONCLUSIONS：The system can help MAH make use of ADR report data to actively monitor drug production quality risks in a timely manner ，investigate risk factors for high-risk production lines ， high-risk varieties and high-risk batch numbers，and assist in decision-making on the direction of risk investigation.
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发布时间：2022-06-21 - 摘要：OBJECTIVE：To d iscuss the monitoring platform of rational use management indexes of key monitored drugs ，and to provide reference for improving their clinical application management. METHODS ：The method of literature research and expert demonstration was adopted ，the indexes of key monitored drugs in medical institutions were put forward. RESULTS & CONCLUSIONS：Finally，Eight general indexes as the list of top 20 drugs purchased by medical institutions ，the specifications of key monitored drugs purchased ，the utilization rate of key monitored drugs of inpatient ，the proportion of key monitored drugs revenue，the increase in the cost of key monitored drugs of inpatient ，the increase in the cost of key monitored drug of single inpatient，the increase of the cost per time of key monitored drugs of inpatient ，the proportion of doctor ’s order review for key monitored drugs were defined. Four major data acquisition projects as the general information of medical institutions ，medical record homepage ，inpatient medication data ，and medical institution drug procurement data were also defined. The monitoring platform of key monitored drugs in medical institutions can provide reference for improving the management of clinical application of key monitored drugs.关键词：Key monitored dr ugs;Monitoring p latform;Data acquisition;Rational drug u se
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发布时间：2022-06-21 - 摘要：OBJECTIVE：To study the improve ment effect of salvianolate on renal interstitial fibrosis （RIF）model rats and its possible mechanism. METHODS ：Totally 50 male SD rats were randomly divided into normal group ，model group ，losartan group （positive control group ，9 mg/kg）and salvianolate low-dose and high-dose groups （18，36 mg/kg）according to body weight ，with 10 rats in each group. Except for normal group ，other groups were given adenine 250 mg/kg intragastrically to establish RIF model. After modeling ，administration groups were given relevant medicine intragastrically ，and normal group and model group were given constant volume of normal saline intragastrically ，the volume was 10 mL/kg，once a day ，for consecutive 30 days. After last medication，the serum levels of creatinine （Scr），urea nitrogen （BUN）and 24 h proteinuria （24 h UPro ）were detected by ELISA. HE staining and Masson staining were used to observe the histopathological characteristics and fibrosis of the kidney. The degree of renal tubular injury and glomerulosclerosis were scored ，and the percentage of positive staining area of renal tissue was calculated ； immunohistochemistry and Western blot assay were used to determine the protein expression of Wnt 5a，Wnt5b，and β-catenin. RESULTS：Compared with normal group ，Scr，BUN and 24 h UPro levels ，renal tubular injury score ， glomerulosclerosis score ， the percentage of positive staining area in renal tissue ，the protein expression of Wnt 5a and β-catenin were increased significantly in model group （P＜0.05），while the expression of Wnt 5b protein was decreased significantly （P＜0.05）. Pathological changes such as mesangial hyperplasia ，fibrous tissue increase and inflammatory cell infiltration were observed under microscope. Compared with model group ，above indexes of rats were improved significantly in losartan group ，salvianolate low-dose and high-dose groups （P＜ 0.05），and the effect of salvianolate had dose-dependent trend. CONCLUSIONS ：Salvianolate has the improvement effect on RIF model rats induced by adenine ，and its mechanism may be related to inhibition of Wnt/ β-catenin signal pathway.关键词：Salvianolate;Adenine;Renal interstitial f ibrosis;Renal function;Wnt/β-catenin signal pathway;Rat
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发布时间：2022-06-21 - 摘要：OBJECTIVE：To establish the method for the content det ermination of 4 components in Forsythia suspensa flowers by drying in shade ，vacuum freeze-drying ，oven（30，50，70 ℃）and sun ，so as to evaluate the effects of different drying methods on the main components of F. suspensa flowers and screen the optimal drying method. METHODS ：UPLC method was adopted. The determination was performed on Waters ACQUITY UPLC BEH C 18 column with mobile phase consisted of acetonitrile- 0.1％ phosphoric acid aqueous solution （gradient elution ）at the flow rate of 0.3 mL/min. The detection wavelength was set at 230 nm， and column was 35 ℃. The sample size was 1 μL. Euclidean closeness（C）i of different drying methods was calculated by TOPSIS comprehensive analysis method ，and the optimal drying method was defined. RESULTS ：The linear range of forsythiaside A ， rutin，forsythin，（+）-pinoresinol-4-O-β-D-glucopyranoside were 0.007 5-0.037 7，0.027 4-0.137 2，0.001 9-0.009 5，0.005 6-0.028 8 µg（all r＞0.999）. RSDs of precision ，stability（32 h）and reproducibility tests were all lower than 2％. The recoveries were 97.27％-102.53％，100.53％-104.11％，98.45％-104.02％，98.66％-104.82％，respectively；and all RSDs ＜3％（n＝3）. The contents were 1.645 8-4.987 9，11.730 2-20.978 0，0.875 5-2.005 0，2.366 0-5.535 7 mg/g. The content of forsythiaside A was the highest after drying at 30 ℃，rutin and （+）-pinoresinol-4- O-β-D-glucopyranoside were the highest after vacuum freeze-drying，forsythiaside was the highest after drying at 50 ℃ . Results of TOPSIS analysis showed that Ci of F. suspensa flowers by drying in shade ，vacuum freeze-drying ，oven（30，50，70 ℃）and sun were 0.079 9，0.553 5，0.495 4， 0.503 8，0.157 9，0.217 2，respectively；the order of Ci was vacuum freeze-drying ＞ 50 ℃ oven drying ＞ 30 ℃ oven drying＞sun drying ＞70 ℃ oven drying ＞ shade drying. CONCLUSIONS：Established method is simple ，reproducible and can be used for the content determination of 4 components in F. suspensa flowers. The samples are preferably dried by vacuum freeze-drying，followed by 50 ℃ oven drying ，30 ℃ oven drying ， and then dried in the sun and oven at 70 ℃ and finally in the shade.关键词：Forsythia suspensa flowers;Main component;Drying in the shade;Oven drying;Vacuum freeze-drying;Drying
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发布时间：2022-06-21 - 摘要：OBJECTIVE：To screen the main effective components of Compound Agrimonia pilosula enteritis capsules and targets of enteritis. METHODS ：UHPLC-MS/MS，MWDB database and relevant literature analysis were used to identify main chemical components in methanol extract of Compound A. pilosula enteritis capsules. TCMSP ，PubChem and UniProt database were adopted to predict and screen the active ingredients and their potential targets. GeneCards and OMIM database were used to predict and screen enteritis related targets ；common targets were screened by R language 4.0.2. The chemical components corresponding to the common targets were matched with the chemical components in the methanol extract of the preparation to obtain the main effective components of the preparation. With the help of STRING database and Cytoscape 3.7.1 software，the protein-protein interaction network was constructed ，and the key targets of the preparation were screened by degree. RESULTS ： A total of 48 compounds were identified ，including 13 phenolic acids ，10 alkaloids，8 flavonoids，6 terpenoids，6 other compounds，3 lipids，1 tannin and 1 organic acid. Compared with the network pharmacology data ，apigenin，luteolin，quercetin （3，7-di-O-methylquercetin，Quercetin-3-O-β-D-galactoside，Quercetin-7-O-glucoside，Quercetin-3-O-β-D-glucoside），palmatine， protocatechuic acid- 4-glucoside and 3，4-dimethoxycinnamic acid were the main effective components. The key targets for the treatment of enteritis included RELA ，APP，CCND1，EGFR，INS，ESR1，IL6，NCOA1，CASP8，FOS. CONCLUSIONS ：A total of 9 main effective components （including apigenin ，luteolin，quercetin，etc.）and 10 key targets for enteritis （including RELA，APP，CCND1，etc.）of Compound A. pilosula enteritis capsules are found.关键词：Compound Agrimonia pilosula enteritis capsules;Network pharmacology;Chemical components;Enteritis;Targets
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发布时间：2022-06-21 - 摘要：OBJECTIVE：To esta blish a method for si multaneous determination of 5 components in the branch and root of Juglans mandshurica as gallic acid ，ellagic acid ，1，6-di-O-galloyl-β-D-glucose，1，2，6-tri-O-galloyl-β-D-glucose and 1，2，3， 6-tetra-O-galloyl-β-D-glucose，and to analyze the content difference of above 5 components between the branch and root samples. METHODS：HPLC method was adopted. The determination was performed on Agilent Poroshell 120 SB-C18 column with mobile phase consisted of water （containing 0.2％ formic acid ）-acetonitrile （containing 0.2％ formic acid ）. A gradient elution was performed at a flow rate of 0.3 mL/min. The column temperature was 30 ℃ and the detection wavelength was 270 nm. The sample size was 5 μL. Independent samples t-test and partial least squares-discriminant analysis （PLS-DA）were applied for statistical analysis of 5 components. RESULTS ：The linear range of gallic acid ，ellagic acid ，1，6-di-O-galloyl-β-D-glucose，1，2， 6-tri-O-galloyl-β-D-glucose and 1，2，3，6-tetra-O-galloyl-β-D-glucose were 0.989-63.3，1.58-101，1.01-64.7，3.31-212，3.34-214 μg/mL （r≥0.997 3），respectively. RSDs of precision ，reproducibility and stability tests （12 h）were all lower than 3.2％. The average recoveries of the 5 components were 103.2％（RSD＝4.85％），99.1％（RSD＝2.80％），101.5％（RSD＝1.31％），102.9％（RSD＝ 2.73％）and 104.7％（RSD＝1.28％），respectively. The average contents of the above components in the branch of J. mandshurica were 0.296 5，0.621 1，0.562 5，3.111 7 and 3.451 3 mg/g，respectively. The average contents of above components in the root were 0.673 4，2.755 5，0.964 0，2.946 6 and 4.836 4 mg/g，respectively. The total contents of the 5 components in the branch and roo t of J. mandshurica were 8.043 2 and 12.175 9 mg/g，respectively. The contents of gallic acid ，ellagic acid and 1，6-di-O-galloyl- β-D-glucose in roots were significantly higher than those in branches （P＜0.05 or P＜0.01）. There were no significant differences in the contents of the other 2 components and the total contents of the 5 components in branches and roots （P＞0.05）. The cumulative interpretability （R 2X，R 2Y） and cumulative predictability （Q 2） of the model established by PLS-DA were 0.943，0.745，and 0.710 respectively. The model load diagram showed that the distance between the ellagic acid and the origin was the farthest ，and only variable projection importance of the content of the ellagic acid was greater than 1. CONCLUSIONS：The established method can be used for the content determination of 5 components in the branch and root of J. mandshurica . Except for 1，2，6-tri-O-galloyl-β-D-glucose，the contents of other 4 components and total contents of the 5 components in the root of J. mandshurica are higher than those of the branch. Ellagic acid is selected as the potential marker for discriminating the branch and root samples.关键词：Juglans mandshurica;Branch;Root;Gallic acid;Ellagic acid;Tannins;Content determination
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发布时间：2022-06-21 - 摘要：OBJECTIVE：To stu dy the regulation effects of Huanglian jiedu decoction on M 1 and M 2 macrophage polarization in atherosclerosis （AS）model mice ，and to elucidate its mechanism of AS prevention and treatment. METHODS ：Sixty ApoE －/－ male mice were randomly divided into blank control group ，model group ，simvastatin group [positive control ，5 mg/（kg·d）]， Huanglian jiedu decoction low-dose ，medium-dose and high-dose groups [ 5，10，20 mg/（kg·d），by crude drug] ，with 10 mice in each group. Except for blank control group ，other groups were given high-fat diet to induce AS model. After modeling ， administration groups were given relevant medicine intragastrically ；blank control group and model group were given normal saline intragastrially，once a day ，for consecutive 4 weeks. After medication ，the contents of triglyceride （TG），total cholesterol （TC）， low density lipoprotein cholesterol （LDL-C） and high density lipoprotein cholesterol （HDL-C） in serum were detected by automatic biochemical analyzer. Sirius red staining was used to observe the formation of collagen fibers in the aorta of mice. The serum contents of iNOS and CD 206 were determined by ELISA. mRNA expression levels of IL- 1β，iNOS，TNF-α，YM1 and Fizz1 in the aorta were detected by RT-PCR. RESULTS ：Compared with blank control group ，the serum contents of TC ，TG， LDL-C and iNOS ，mRNA expression levels of IL- 1β，iNOS，TNF-α in the aorta were significantly increased in model group（P＜ 0.05 or P＜0.01），while the serum contents of HDL-C and CD 206 and mRNA expression levels of IL- 10，YM1，Fizz1 in the aorta were significantly decreased （P＜0.01）. There was a thick layer of collagen fibers under the endothelium of aorta. Compared with model group ，above serum indexes of mice were improved significantly in administration groups （P＜0.05 or P＜0.01）；mRNA expression levels of IL- 1 ，iNOS and TNF-α in the aorta in Huanglian jiedu decoction medium-dose and high-dose groups were decreased significantly （P＜0.01），while mRNA expression levels of IL- 10，YM1 and Fizz 1 were increased significantly （P＜0.05 or P＜0.01）. The vascular endothelium was relatively smooth. CONCLUSIONS ：Huanglian jiedu decoction can inhibit the polarization of M 1 macrophages and promote the polarization of M 2 macrophages，reduce the inflammatory reaction ，maintain the stability of atherosclerotic plaque in artery ，so as to play the role of anti-AS.关键词：Huanglian jiedu decoct ion;Atherosclerosis;Macrophage polarization;Mice
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发布时间：2022-06-21 - 摘要：OBJECTIVE：To analyze the chemotypes of volatile components from Perillae Folium of different germplasms ，and to investigate the relationship of germplasm and leaf color with chemotype. METHODS ：The fingerprints of volatile components from 30 batches of Perillae Folium were prepared by GC-MS with P 4 peak as reference. Similarity Evaluation System for TCM Chromatographic Fingerprint （2004A edition ）was applied to evaluate the similarity and confirm common peaks. The volatile components of Perillae Folium were determined by the same GC-MS method. Qualitative Navigator （B.08.00）software was used to analyze and compare with NIST 17.0 standard mass spectrum database. The compounds corresponding to the peak were analyzed ； clustering analysis was carried out with Origin 2018 software. RESULTS ：There were 13 common peaks in the fingerprints of volatile components from 30 batches of Perillae Folium . The similarities were 0.13-1.00. Totally 54 components were identified from 30 batches of Perillae Folium of different germplasm. Cluster analysis showed that 30 batches of Perillae Folium samples could be clustered into three categories ；among them ，SCY-1，YNT-9，YNX-17，YN-28 were clustered into one category ，with phenylpropanoid-elemicin（PP-e as ）the main volatile component ，being PP-e type ；GS-4，GS-7，GS-11，GS-19，HBA-14， HBA-20，GZZ-8，LN-39，GSL-27，GSQ-32，GSQ-33，GST-31，YNW-12，LN-38 were clustered into one category ，and the content of perilla ketone （PK）in them was the highest except for LN- 38， being PK type [the content of phenylpropanoid-apiol（PP-a）in LN- 38 was higher than that of perilla ketone ，being PP-a type] ；HBS-2，HBS-3，HBS-6， C201859）HBS-15，HBS-16，HBS-24，HBS-25，GX-26，SXS-30，SCC- 36，RB-37，SC-29 were clustered into one category ，and thecontent of perillaldehyde （PA）was the highest ，being PA type.The color characteristics of Perillae Folium of different germplasm showed that Perilla frutescens （L.） Britt. var.frutescens with green leaves on both sides was PK type ，while P. frutescens （L.）Britt. var. arguta with purple leaves on one or both sides was PA type ，and P. frutescens （L.） Britt var. auriculato-dentata C. Y. Wu et Hsuan ex H. W. Li was PP-e type. CONCLUSIONS：The chemotype of volatile components in Perillae Folium have a certain corresponding relationship with their leaf colors. Most of P. frutescens （L.）Britt. var. arguta with purple leaves on one side or both sides are PA type. P. frutescens （L.） Britt. var. acuta （Thunb.）Kudo，P. frutescens （L.）Britt var. auriculato-dentata C. Y. Wu et Hsuan ex H. W. Li and P. frutescens （L.）Britt. var. frutescens with green leaves on both sides do not belong to PA type ，among which P. frutescens （L.）Britt var. frutescens is PK type ，while P. frutescens （L.）Britt var. auriculato-dentata C. Y. Wu et Hsuan ex H. W. Li is mostly PP-e type.关键词：Perillae Folium;GC-MS;Volatile components;Chemotypes;Fingerprint
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发布时间：2022-06-21 - 摘要：OBJECTIVE：To stud y the effects of sinapine thiocyanate （ST） on the proliferation ，epithelial mesenchymal transformation（EMT）and metastasis of human cutaneous squamous cell carcinoma SCL- 1 cells，and to investigate its possible mechanism. METHODS ：Human cutaneous squamous cell carcinoma SCL- 1 cells were divided into blank control group （0.1％ DMSO） and ST different concentration groups （5，10，20 μmol/L）. CCK- 8 assay，5-ethynyl-2′-deoxyuridine（EDU）test， scratch test and Transwell chamber invasion test were adopted to test the proliferation ，migration and invasion ability. The expression of N-cadherin and E-cadherin were detected by Western blot and immunofluorescence assay . Other SCL- 1 cells were collected and divided into blank control group （0.1％ DMSO），ST group （20 μmol/L），ST+NSC228155 group [ 20 μmol/L ST+100 μmol/L NSC228155（EGFR agonist ）] and ST+SC 79 group [ 20 μmol/L ST+20 μmol/L SC79（PI3K/Akt agonist ）]. The proliferation ，migration and invasion ability of SCL- 1 cells in each group were detected by CCK- 8 assay，scratch test and Transwell chamber invasion assay. The expression of epidermal growth factor receptor （EGFR），phosphatidylinositol 3 kinase（PI3K），phosphorylated phosphatidylinositol 3 kinase（p-PI3k），protein kinase B （Akt）and phosphorylated protein Akt （p-Akt）protein of cells in blank control group and ST different concentration groups（5，10，20 μmol/L）were determined by Western blot assay so as to validate the relationship between ST effect and EGFR/ PI3K/Akt signaling pathway. SCL- 1 cells and human normal skin fibroblasts cell WS 1 were divided into blank control group （0.1％ DMSO），ST group （20 μmol//L），ZD1839 group（positive control ，20 μmol//L，EGFR inhibitor ）and LY 294002 group（positive control，20 μmol//L，PI3K/Akt inhibitor ）. CCK- 8 assay was used to detect the cell proliferation in order to evaluate the cells cytotoxicity of ST. RESULTS ：Compared with blank control group ，the proliferation ，migration and invasion ability of SCL- 1 cells were significantly decreased in 5，10，20 μmol/L ST groups（P＜0.05）. Western blot and immunofluorescence assay showed that the expression of N-cadherin in SCL- 1 cells were decreased significantly in 5，10，20 μmol/L ST groups（P＜0.05），while the protein expression of E-cadherin was increased significantly （P＜0.05）；the protein expressions of EGFR ，p-PI3K and p-Akt were significantly decreased （P＜0.05）. Compared with ST group ，the proliferation ，migration and invasion ability of SCL- 1 cells were increased significantly in ST + NSC 228155 group and ST + SC 79 group （P＜0.05）. Compared with blank control group ，the proliferation ability of WS 1 cells had no significant change in ST group ，while the proliferation ability of SCL- 1 cells was decreased significantly （P＜0.05）；the proliferation ability of the two kinds of cells were decreased significantly in ZD 1839 group and LY 294002 group（P＜0.05）. Compared with ST group ，the proliferation ability of WS 1 cells was decreased significantly in ZD1839 group and LY 294002 group（P＜0.05），but there was no significant difference in the proliferation ability of SCL- 1 cells （P＞0.05）. CONCLUSIONS ：ST may inhibit the proliferation ，EMT and metastasis of SCL- 1 cells through inhibiting the activation of EGFR/PI 3K/Akt signaling pathway ，and its side effects are few.
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发布时间：2022-06-21 - 摘要：OBJECTIVE：To estab lish fingerprint of Duzhong butiansu pill s，analyze its chemical pattern recognition ，and determine the contents of 7 components in Duzhong butiansu pills ，so as to provide reference for the quality control of the preparation. METHODS ：HPLC method was adopted. The determination was performed on Pntulips BP-C 18 Plus column with 0.2％ phosphoric acid water-acetonitrile as mobile phase （gradient elution ）at the flow rate of 1.0 mL/min. The detection wavelength was set at 330 nm，and column temperature was 35 ℃. The sample size was 20 μL. With paeonol as the reference，the HPLC fingerprints of 12 batches of Duzhong butiansu pills （S1-S12） were established with Similarity Evaluation System for TCM Chromatographic Fingerprint （2012 edition）； common peaks were determined and the similarity was evaluated. The chromatographic peaks were identified by comparing with the reference substance. SPSS 21.0 and SIMCA 13.0 software were used for cluster analysis and principal component analysis ，and 22 common peaks were evaluated. The contents of the identified components in 12 batches of samples was determined by the above HPLC method. RESULTS ：A total of 22 common peaks were identified in the HPLC fingerprint of 12 batches of Duzhong butiansu pills ，and the similarity was no loss than 0.960. There were 7 chemical components identified ，which were gallic acid （peak 1），chlorogenic acid （peak 3），liquiritoside（peak 6），hyperoside （peak 7），verbascoside（peak 8），icariin（peak 14）and paeonol （peak 15）. Among the 12 batches of samples ，S1，S3-S5，S7， S9 and S 11 were classified as one category ，S2，S10 and S 124Y091 were clustered into one category ，S6 was one category and S was one category. The 22 common peaks were divided into three principal components. The characteristic value （15.130） and contribution rate （68.775％） of principal component 1 were the largest ，and the score coefficients of peak 3（0.305）and peak 4（0.298）were the highest. Among 12 batches of samples，the cont ents of above 7 components were 18.196 231.951 3，0.000 6-0.049 4，0.234 8-0.415 9，0.039 5-0.079 1，0.053 5-0.249 3，0.000 5-0.000 8，0.646 4-1.146 9 mg/g，respectively. CONCLUSIONS：HPLC fingerprint of Duzhong butiansu pills is established successfully. Twelve batches of samples are clustered into 4 category. Peak 3（chlorogenic acid ）and peak 4（unknown）may be the important factors causing the difference of samples. The content of gallic acid is the highest among the 7 components.关键词：Duzhong butiansu pills;HPLC;Fingerprint;Chemical pattern recognition;Content determination
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发布时间：2022-06-21 - 摘要：OBJECTIVE：To study the effec ts of Tibetan Codonopsis tralictrifolia extract （called“ZDS”for short ） on collagen-induced arthritis （CIA）model rats and its mechanism. METHODS ：Eight of 48 rats were randomly selected as normal control group （normal saline ），and the remaining 40 rats were used to establish CIA model. After successful modeling ，the rats were randomly divided into model group （normal saline ），ZDS low-dose ，medium-dose and high-dose groups （0.44，0.88，1.76 g/kg，by crude drug ），dexamethasone group （positive control ，0.002 5 g/kg），with 8 rats in each group. They were given relevant medicine intragastrically ，the volume of 400 μL，once a day ，for consecutive 28 days. The body weight of rats were weighed before medication （0 d），7，14，21 and 28 days after medication ；and arthritis indexes were scored. The pathological changes of the knee joint synoviual tissue were observed after last medication. The thymus index ，spleen index ，the levels of serum inflammatory factors （IL-1β，TNF-α，IL-6），protein expressions of NF-κB p65，p-NF-κB p65，IκB and p-IκB in synovial tissue were detected. RESULTS ：Compared with normal control group ，the body weight （14，21，28 days after administration ）of rats in model group was significantly reduced （P＜0.05）；the arthritis index score （before administration and different administration time）was significantly increased （P＜0.05）；the joint synovial tissue was pathologically damaged ；the thymus and spleen index ， inflammation factor level ，the protein expression of p-NF-κB p65 and p-IκB were increased significantly（P＜0.05），while the protein expression of IκB was decreased significantly（P＜0.05）. Compared with model group ，the level of IL- 1β was decreased significantly in ZDS low-dose group （P＜0.05）. Body weight of rats （21，28 days after administration ）were increased significantly in ZDS medium-dose and high-dose groups ，dexamethasone group （P＜0.05），while arthritis index score （14，21，28 days after administration ） was decreased significantly （P＜0.05）. The pathological damage of joint synovial tissue was significantly relieved ；thymus and spleen index ，inflammation factor level ，the protein expression of p-NF-κB p65 and p-IκB were significantly reduced，while the protein expression of IκB was significantly increased （P＜0.05）. CONCLUSIONS ：ZDS can improve CIA model rats to some extent ，and its mechanism may be related to the inhibition of NF-κB signaling pathway.关键词：Rheumatoid arthritis;Codonopsis tralictrifolia;Extract;Collagen-induced arthritis;NF-κB signaling pathway;Rat
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发布时间：2022-06-21 - 摘要：OBJECTIVE：To establish the method for the con tent determination of related substances in belinstat. METHODS ： HPLC method was adopted and the principal component self-control comparison method with correction factor was used to calculate the contents of related substances. The determination was performed on ODS-AM column with 1.02％ potassium dihydrogen phosphate buffer （pH value adjusted to 3.5 with phosphoric acid ）-acetonitrile（85∶15，V/V）as mobile phase A ，1.02％ potassium dihydrogen phosphate buffer （pH value adjusted to 3.5 with phosphoric acid ）-acetonitrile（30 ∶ 70，V/V）as mobile phase B （gradient elution ），at the flow rate of 1.0 mL/min. The column temperature was set at 30 ℃，and the detection wavelength was 220 nm. The sample size was 10 μL. RESULTS：The linear ranges of belinstat and impurities A ，D，F，G，H were 0.113-1.693， 0.050-1.496，0.117-1.750，0.098-1.471，0.120-1.799，0.100-1.506 μ g/mL（r≥0.999 7）. The correction factors of the last 5 impurities were 1.0，1.0，1.2，1.5，1.0；the detection limits were 0.250，0.590，0.490，0.600，0.500 ng，respectively. The quantification limits were 0.500，1.170，0.980，1.200，1.000 ng，respectively. The recoveries were 90.18％-111.48％（RSD＝ 1.52％-4.78％，n＝9）. RSDs of stability （100 h）and precision tests were no more than 16％，and the durability was good. Impurities A ，D and H were detected in 3 batches of belinlestat ，the contents were 0.030％-0.038％，0.019％-0.022％ and 0.012％-0.013％，respectively. The contents of other maximum monomer impurities were 0.012％-0.013％ and the total impurities were 0.075％-0.084％. Impurities B ，C，F，G were not detected. CONCLUSIONS ：The method for the content determination of related substances in belinstat has been successfully established ，and the method is accurate and specific.关键词：Belinostat;Related substances;HPLC;Principal component self-control comparison method wit h correct ion factor
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发布时间：2022-06-21 - 摘要：OBJECTIVE：To evaluate the cost-utility of the pan-genotypic direct-acting antivirals （DAAs）in the treatment of patients with chronic hepatitis C infection ，and to provide pharmacoeconomic evidence for relevant health care decisions. METHODS：A Markov model was established from a societal perspective with newly diagnosed chronic hepatitis C patients in China as the target population ，and analyzed quality-adjusted life years （QALYs）and incremental cost-utility ratios （ICERs）of patients with chronic hepatitis C with sofosbuvir/velpatasvir ，glecaprevir/pibrentasvir，sofosbuvir+coblopasvir. Sensitivity analysis was used to verity the robustness of the results. RESULTS ：Glecaprevir/pibrentasvir increased QALYs by 0.002 1 and costs by 25 021 RMB，compared to sofosbuvir/velpatasvir ；its ICERs was 12 129 031 yuan/QALY（willingness to pay threshold was 70 892 yuan/QALY），which had no cost-utility ；glecaprevir/pibrentasvir need to cut down the price by 64.65％ to have cost-utility. Sofosbuvir+coblopasvir increased QALYs by 0.002 0 and saved costs by 515 yuan，so it was the optimal regimen which was cost-saving. Sensitivity analysis showed that SVR rates and drug prices were the most influential factors. The probability of having cost-utility for sofosbuvir+coblopasvir was higher than glecaprevir/pibrentasvir. CONCLUSIONS ：Glecaprevir/pibrentasvir need to reduce the price to achieve better affordability. Sofosbuvir+coblopasvir shows economical advantage.关键词：Chronic hepatitis C virus infection;Direct-acting antivirals;Cost-utility analysis;Markov model;Pan-genotypic
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发布时间：2022-06-21 - 摘要：OBJECTIVE：To excavate and evaluate ADR signals of SGLT 2 inhibitors as canagliflozin ，dapagliflozin and empagliflozin，and to provide reference for rational drug use in the clinic. METHODS ：The proportional reporting ratio （PRR）and reporting odds ratio （ROR）were used to find the adverse drug reactions （ADR）signal of SGLT 2 inhibitors as canagliflozin ， dapagliflozin and empagliflozin from the second quarter of 2013 to the third quarter of 2020 in the US FDA Adverse Event Reporting System （FAERS）. The basic information （including gender ，age，reporting year ，reporting country ，severe ADR ）and safety warning signals of corresponding patients in ADR report were analyzed. RESULTS ：Among 6 029 375 ADR reports ，SGLT2 inhibitors of 43 807 ADR reports were concomitant and suspected drugs ；there were 19 301 ADR reports of canagliflozin ，10 960 ADR reports of dapagliflozin ，13 546 ADR reports of empagliflozin. Except for the ADR patients with unknown gender and missing age ，the gender distribution of the included reports was balanced ，mainly in the range of 50-75 years old. The reporting year was mainly in 2018，and the main reporting country was the United States ，with“hospitalization or prolonged hospitalization ” as the main serious ADR. A total of 573 ADR signals were obtained ，involving 26 systems，mainly focusing on metabolic and nutritional diseases ，endocrine disorders ，kidney and urinary system disease ，infection and invasion diseases ，etc. The results showed that there were 14 main ADR signals in the top 10 ADR of canagliflozin ，dapagliflozin and empagliflozin. The strongest ADR signals of dapagliflozin and empagliflozin were ketoacidosis （PRR＝119.64/140.11，95％CI lower limit of ROR ＝148.28/ 178.78）and fungal infection （PRR＝47.76/34.77，95％ CI lower limit of ROR ＝50.69/36.28）；except above signals in addition ， toe amputation （PRR＝489.79，95％CI lower limit of ROR ＝520.15）and osteomyelitis （PRR＝61.42，95％CI lower limit of ROR＝65.38）were strong in the ADR signals of canagliflozin. CONCLUSIONS ：SGLT2 inhibitors have a higher security risk in metabolic and nutritional diseases ，endocrine disorders ，kidney and urinary system ，and infection and intrusion diseases. Dapagliflozin，canagliflozin and empag liflozin are prone to cause ADR such as ketoacidosis and fungal infection ，while canagliflozin is easy to cause ADRs such as toe amputation and osteomyelitis.
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发布时间：2022-06-21 - 摘要：OBJECTIVE：To investigate the risk factors for the recurrence of ischemic stroke after secondary prevention ，and to observe the effect of glutathione on 4-HNE. METHODS ：Totally 97 patients with ischemic stroke relapse within one year were treated from Oct. 2017 to Oct. 2019 in 3 hospitals as the Second Affiliated Hospital of Shandong First Medical University due to cerebral thrombosis or cerebral embolism as observation group ，and 97 non-recurrence patients in the same period were paired as control group. The patients in the observation group were randomly divided into conventional treatment group （49 cases）and drug intervention group （48 cases）. The patients in conventional treatment group received routine treatment such as cerebral blood flow recanalization， improving circulation ， controlling blood pressure ， maintaining blood glucose ， treating hyperlipidemia and arrhythmia during hospitalization. Drug intervention group was additionally given Glutathione for injection 1.8 g intragastrically ， once a day ，on the basis of conventional treatment group. 4-HNE concentrations in plasma were determined at admission and 14 days after treatment ，the genetic type of ALDH2 and type of TAST were determined at admission. Multiple liner regression was used to analyze the factors associated with 4-HNE increasing ； conditional Logistic analysis was used to identify independent risk factors resulting to ischem ic stroke recurrence after secondary prevention. RESULTS ：The plasma concentration of 4-HNE at admission and the percentage of arte ry atherosclerosis patients in observation group were significantly higher than control group（P＜0.05）. The distribution of each ALDH2 genotype in 2 groups complied with Hardy-Weinberg genetic equilibrium （P＞ 0.05）. The proportion of patients carrying ALDH2*2 allele in observation group （50.50％）was significantly higher than control group（36.08％）（P＜0.05）. ALDH2*2 allele [ B＝2.33，95％CI（1.35，5.50），P＝0.03] and artery atherosclerosis [ B＝1.90，95％CI （1.29，3.74），P＝0.04] were significantly associated with the elevation of plasma concentration of 4-HNE；artery atherosclerosis [OR＝ 2.93，95％CI（1.84，4.67），P＜0.01]，stroke family history [OR ＝1.50，95％CI（1.18，1.90），P＝0.04]，elevated plasma concentration of 4-HNE [OR ＝1.34，95％CI（1.11，1.62），P＝0.04] were regarded as independent risk factors associating with ischemic stroke recurrence after secondary prevention. After intervention ，plasma concentration of 4-HNE in drug intervention group and conventional treatment group was significantly lower than before intervention （P＜0.05）；there was no statistical significance between 2 groups（P＞0.05）. CONCLUSIONS ：Stroke family history ，artery atherosclerosis and the elevation plasma concentration of 4-HNE are independent risk factors associating with ischemic stroke recurrence after secondary prevention. Although drug intervention can reduce the elevated plasma concentration of 4-HNE，the effect of additional use of glutathione is not more significant than that of conventional treatment.关键词：Ischemic stroke;Secondary prev ention;Recurrence;Glutathione;4-hydroxynonenal;ALDH2*2 allele;Risk factor
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发布时间：2022-06-21 - 摘要：OBJECTIVE：To systematically evaluate th e efficacy and safety of Compound banmao capsules combined with different chemoradiotherapy in the treatment of primary hepatic carcinoma （PHC）. METHODS ：Retrieved from CBM ，CNKI， Wanfang database ，VIP，PubMed，Embase and Cochrane Library during the inception to Sept. 2020，randomized controlled trial （RCTs），cohort study about Compound banmao capsules combined with different chemoradiotherapy plans （trial group ）versus different chemoradiotherapy plans （control group ）were collected. After literature screening and data extraction ，the quality of included RCTs were evaluated with bias risk evaluation tool recommended by Cochrane system evaluator mannual 5.1.0. Newcastle Ottawa scale was used to evaluate the quality of cohort 502） studies；Rev Man 5.3 software was used for Meta-analysis ；TSA 0.9.5.10 Beta software was used for trail sequential analysis，and GRADE Profiler 3.6.1 software was used for evidence quality evaluation of RCT and cohort studies . RESULTS：A total of 15 RCTs were included ，involving com 1 148 patients. Meta-analysis showed that effective rate of trial group was significantly higher than that of control group [RR ＝0.80，95％CI（0.73，0.88），P＜0.000 01]. The results of subgroup analysis according to different chemotherapy plan showed that the effective rate of trial group combined with TACE and three dimensional conformal radiotherapy were significantly higher than control group （P＜0.05）. The survival rate of trial group was significantly higher than control group [RR ＝0.81，95％CI（0.74，0.89），P＜0.000 1]；the results of subgroup analysis according to different survival time showed that 1-year，2-year and 3-year survival rates of trial group were significantly higher than control group（P＜0.05）. The incidence of myelosuppression in trial group was significantly lower than control group ，and the natural killer cell count and T cell count of trial group were significantly higher than control group （P＜0.05）. There was no statistical significance in AFP content and liver function index between 2 groups（P＞0.05）. Trial sequential analysis showed that there was definite evidence for better effective rate of Compound banmao capsules combined with TACE. GRADE evaluation results showed that the evidence level of effective rate was intermediate ，the evidence level of survival rate and incidence of myelosuppression was low，and other indicators were very low. CONCLUSIONS ：Compound banmao capsules combined with different chemoradiotherapy in the treatment of PHC has significant efficacy and good safety ，especially in combination with TACE ，and the evidence level of effective rate is intermediate.
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发布时间：2022-06-21 - 摘要：OBJECTIVE：To study influential factors for medication compliance of phosphate binder in patients with maintenance hemodialysis and the effects of pharmacist intervention ，and to improve medication compliance and the effects of disease control. METHODS ：The patients with maintenance hemodialysis who were treated in the blood purification center of our hospital from Jun. to Dec. ，2019 were selected for questionnaire survey. The questionnaires involved general information ， medication compliance of phosphate binder ，disease and medicine related knowledge ，social support ，self-efficacy. The t-test，χ2 test and multivariate Logistic regression analysis were used to analyze influential factors for medication compliance. The patients were randomly divided into pharmaceutical intervention group and non-intervention group. Intervention group were provided with pharmaceutical care for 3 months according to risk factors. Blood phosphorus level and medication compliance was compared between 2 groups. RESULTS ：Totally 298 patients completed the survey （effective recovery rate of 96.1％）. Among them ，163 patients（54.7％）had good adherence to phosphate binder ，while 135 patients（45.3％）had poor compliance. Results of single factor analysis showed that medication compliance of phosphate binder was closely associated with age ，dialysis duration ， parathyroid hormone levels ，total daily dose ，daily dose of phosphate binder ，disease and medicine related knowledge scores ， social support ，self-efficacy（P＜0.05）. Results of multivariate Logistic regression analysis showed that total daily dose ，daily dose of phosphate binder ，disease and medicine related knowledge scores ，social support and self-efficacy were the influential factors for medication compliance （P＜0.05 or P＜0.01）. Medication compliance ，disease control status ，disease and medicine related knowledge score ， social support and self-efficacy in pharmaceutical intervention group were significant improved ， blood phosphorus level was significant lower ，compared with non-intervention group （P＜0.05）. CONCLUSIONS ：Independent risk factors influencing medication compliance of phosphate binder include total daily dose ，daily dose of phosphate binder ，disease and medicine related knowledge scores ，social support and self-efficacy. The patients with maintenance hemodialysis have poor compliance to phosphate binder. Pharmacists should take individualized and targeted intervention measures for the above risk factors，which can effectively improve the medication compliance and disease prognosis of patients.关键词：Maintenance hemodialysis;Phosphate binder;Medication compliance;Hyperphosphatemia;Pharmaceutical
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发布时间：2022-06-21 - 摘要：OBJECTIVE：To establish the m ethod for the simultaneous determination of 6 carbohydrate related substances in glucose as fructose ，maltose，isomaltose，maltotriose，maltotetraose and maltopentaose. METHODS ：HPLC-ELSD was adopted. The determine was performed on XBridge Amide column with mobile phase consisted of acetonitrile-water （75∶25，V/V）at a flow rate of 0.5 mL/min. The column temperature was set at 30 ℃，and the sample size was 10 L. The detector was evaporative light scattering detector ，the carrier gas was nitrogen ，the gas pressure was 40 psi，the evaporation temperature was 80 ℃，the drift tube temperature was 80 ℃，and the gain was 100. RESULTS ：The linear range of 6 carbohydrate related substances were 5.99-59.88， 9.90-98.96，9.92-99.19，5.97-59.74，4.03-40.32，5.89-58.89 μg/mL（r＞0.999 0）. The quantitation limits were 1.5，1.5，1.5，3.0， 3.0 and 3.0 μg/mL，respectively. The detection limits were 0.5，0.5，0.5，1.0，1.0，1.0 μg/mL，respectively. RSDs of precision ， stability（12 h）and reproducibility tests were all lower than 2.0％. The average recoveries were 95.87％-98.59％（RSD＝1.04％，n＝ 9），95.66％-99.84％（RSD＝1.20％，n＝9），96.11％-98.97％（RSD＝1.04％，n＝9），95.06％-99.11％（RSD＝1.25％，n＝9）， 95.69％-98.22％（RSD＝0.83％，n＝9），95.34％-98.56％（RSD＝1.01％，n＝9）. The contents of 6 carbohydrate related substances in 9 batches of glucose were 1.26-2.22，2.55-3.36，2.37-3.37，1.28-2.01，0-2.11 and 0-1.89 mg/g，respectively. CONCLUSIONS ： Established method is accurate and sensitive ，and can be used for the detection of carbohydrate related substances in glucose.关键词：Glucose;Carbohydrate;Related substance;HPLC-ELSD
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发布时间：2022-06-21
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