最新刊期
      卷 31 ， 期 9 ， 2020
      • HE Rui,GE Jing,HE Mengjiao,LU Yun
        Vol. 31, Issue 9, (2020)
        摘要：OBJECTIVE：To provide reference for the improvement of centralized drug procurement system in China. METHODS：Based on gaming theory ， it was assumed that all drug manufacturers participating in the bidding were rational ，and their goals were to maximize their own interests. Drug manufacturers participating in the bidding did not know the quotations of other drug manufacturers participating in the bidding before the bid opening. There was no collusion among drug manufacturers participating in the bidding ，and the quotations of each manufacturer were repeated as small probability events ，which meant it was basically impossible to occur. Under the above assumptions ，a static game model with incomplete information was constructed for the bidding process to analyze the influential factors of price reduction of drug quantity purchasing ，then related suggestions were put forward. RESULTS & CONCLUSIONS ：The gaming model was established successfully. The model covered the number of enterprises with the qualification to participate in the centralized procurement of drugs ，the number of the most successful enterprises and their declared price ，cost，quotation strategy ，the average agreed purchase volume after bidding ，the probability of winning the bidding ，the expected income after winning the bidding ，etc. The larger number of unsuccessful manufacturers ，the lower upper and lower limits （but the lower limits could not lower than cost price ）of drug price ，and the greater agreed purchase quantity were all beneficial to acquire a lower selected price under this model. Based on this ，the author suggests that the government should actively construct the competitive pattern of N＞n（the number of enterprises applying for qualification is greater than the number of enterprises that can be selected at most ），set a reasonable price upper and lower limit and specify the purchase quantity when improving the centralized bidding system of drugs in China.  
        关键词：Drug;Quantity purchasing;Price;Gaming theory;Influential factors   
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        发布时间：2022-06-21
      • GUO Zhigang,XU Ziyue,ZHANG Xi,ZHENG Liguang,GUAN Xiaodong,SHI Luwen
        Vol. 31, Issue 9, (2020)
        摘要：OBJECTIVE：To provide reference for improving the equity of medicine in China ，and to provide reference for promoting the full coverage policy for essential medicine. METHODS ：Taking hypertension essential medicines full coverage policy in 4 areas of Taizhou in Zhejiang province as an example ，the electronic health records of patients in baseline year and the first ， second and third years after the implementation of the full coverage policy of hypertension were collected. The catastrophic expenditure of family drugs was used to measure the medicine cost burden ，and the effects of policy on the equity and change of local medicine cost burden were analyz ed by means of concentration index and its decomposition method. RESULTS ：With the increase of the proportion of patients taking free medicine ，the incidence of catastrophic expenditure on household medicines in the high，middle and low income group decreased year by year generally （decreasing from 6.3％，12.0％，16.4％ of baseline year to 4.7％，8.9％，12.4％ at the third year after the implementation of the policy ）；the gap among the three groups was in narrowed trendency. The concentration indexes of the baseline year and the first ，second，third year after the implementation of policy were －0.198，－0.186，－0.181，－0.202，the policy contribution rates of which were 0，－1.335％，－4.507％ and 1.936％；and the policy contribution rates in the change of the yearly concentration index were 20.8％，95.0％ and 57.6％. CONCLUSIONS ：The implementation of the full coverage policy for essential medicines is conducive to improving the equity of the medicine expenditure burden. The effect is affected by the implementation of policies and supporting systems ，but the comprehensive promotion of the equity of medicine requires multi-policy synergy.  
        关键词：Taizhou city;Essential medicine;Full coverage policy;Equity;Hypertension;Medicine expenditure affordability   
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        发布时间：2022-06-21
      • YANG Shiyong,HE Yi,SONG Daqiang,WU Xu,ZHANG Zhuo
        Vol. 31, Issue 9, (2020)
        摘要：OBJECTIVE：To observe the p rotective effects of resveratrol （Res）on LPS-induced acute lung injury （ALI）model mice，and to explore its possible mechanism based on TLR 4/NF-κB pathway. METHODS：Kunming mice were divided into normal group，model group ，positive control group （dexamethasone，0.5 mg/kg），Res low-dose ，medium-dose and high-dose groups （50， 100，200 mg/kg），with 10 mice in each group. Normal group and model group were given normal saline intragastrically ，once a day，for 7 days；positive control group were intraperitoneally injected with Dexamethasone sodium phosphate injection ，once a day，for 3 days；Res groups were given relevant medicine intragastrically ，once a day ，for 7 days. After last administration ，all the mice except the normal group were dripped LPS （5 mg/kg）into the nose to induce ALI model. The apoptosis of neutrophils in BALF was observed by Hoechst 33242 staining；the apoptosis rate of neutrophils were detected by flow cytometry. The contents of IL- 6 and TNF-α in the plasma were detected by ELISA. After wet mass to dry mass （W/D）ratio of lung was E-mail：492234709@qq.com calculated，the morphological characteristics of lung tissue were observed by HE staining. Western blotting assay was used to detect the expression o f TLR 4 and NF-κ B in lung tissue. RESULTS ：In normal group ，there were few apoptotic neutrophils in the BALF ，and the lung tissue structure was intact ， without edema，hyperemia，exudation，inflammatory cell infiltration or other inflammatory manifestations. In model group ，the number of apoptotic neutrophils in BALF increased ，and the apoptotic rate of neutrophils were enhanced significantly （P＜0.01）； edema and hyperemia of lung tissue were significantly increased ，and the red consolidation area was observed ；the contents of IL- 6 and TNF-α in plasma，the ratio of lung W/D，the relative expression of TLR 4 and NF-κB in lung tissue were significantly increased （P＜0.01）. Compared with model group ，the number of apoptotic neutrophils in BALF were increased ，and the apoptotic rate of neutrophils were enhanced significantly （P＜0.05 or P＜0.01）above symptoms of lung tissue were improved to different extents ； the contents of IL- 6 and TNF-α in plasma，lung W/D ratio as well as relative expression of TLR 4 and NF-κB in lung tissue（except for Res low-dose group ）in administration groups were decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS ：Res has a protective effect on ALI model mice ，the mechanism of which may be related to reducing the generation of inflammatory cytokines TNF-α and IL-6 by inhibiting TLR 4/NF-kB expression.  
        关键词：Resveratrol;Acute lung injury;TLR4;NF-κB;Inflammatory cytokines;Mechanism;Mice   
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        发布时间：2022-06-21
      • DENG Kezhong,LIU Cong,CHANG Meiyan,ZONG Qi,XIONG Ying
        Vol. 31, Issue 9, (2020)
        摘要：OBJECTIVE：To sepa rate and identify the phenols compounds in Aurantii Fructus Immaturus ，and to provide reference for basic research of its effective substances. METHODS ：The phenols compounds were isolated and separated by silica gel，HW-40F gel column ，ODS reversed column and preparation HPLC. Their physicochemical properties and spectral data were used to identify the structures. RESULTS & CONCLUSIONS ：Totally 12 compounds were isolated from Aurantii Fructus Immaturus，identified as 6′-O-trans- cinnamoyl- 3，5-dihydroxyphenyl β-D-glucopyranoside（compound 1），methyl 3-（2′，4′- dihydroxy phenyl ）propionate（compound 2），phloroglucinol（compound 3），aurantiside A （compound 4），5，7，4′-trihydroxy-8， 3′-dimethoxyflavone-3-O-6″-（3-hydroxyl-3-methylglutaroyl） β-D-glucopyranoside （compound 5）， aromadendrin-7-O-β-D- glucopyranside（compound 6），hesperidin-7-O-β-D-glucoside（compound 7），naringin（compound 8），hesperidin（compound 9）， narirutin （compound 10），neoeriocitrin （compound 11），eriocitrin （compound 12）. Among them ，compound 1 is a new compound，and compounds 2 and 3 are isolated from Critus for the first time.  
        关键词：Aurantii Fructus Immaturus;Chemical constituents;Phenols compounds;Isolation;Identification   
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        发布时间：2022-06-21
      • ZHANG Jingzhi,ZHAO Danqing,WANG Zhengrong,JIA Jinyan,YANG Lin,ZHANG Shengsheng,LIU Xinlei,WU Qing,PAN Wei
        Vol. 31, Issue 9, (2020)
        摘要：OBJECTIVE：To establish QAMS method for simultaneou s determination of 7 effective components in Yao medicine Yueli yaomi spray ，such as α-cyperone，α-pinene，β-pinene，limonene，β-elemene，caryophyllene oxide and ligustilide ， so as to provide method reference for the quality control of the preparation. METHODS ：GC method was adopted. The determination was performed on DB- 1701P capillary column ，using nitrogen as carrier gas. The temperature of the hydrogen flame ion detector was 240 ℃. The temperature was programmed ，the inlet temperature was 240 ℃，the injection volume was 1 μL and the split ratio was 20 ∶ 1. Using limonene as internal reference ，the relative correction factors of other 6 components were calculated，the contents of them were calculated with relative correction factors ，and then compared with the results of internal standard method （using naphthalene as internal standard ）. RESULTS ：The mass concentration linear range of α-cyperone， α-pinene，β-pinene，limonene，β-elemene，caryophyllene oxide and ligustilide were 0.008 9-1.110 0，0.028 3-3.540 0，0.020 5- 2.560 0，0.023 0-2.880 0，0.016 3-2.035 0，0.013 1-1.640 0，0.008 3-1.040 0 mg/mL（all r＞0.999 0）；the limits of quantification were 0.005 6，0.013 1，0.011 4，0.018 6，0.010 8，0.008 9，0.004 5 mg/mL；the detection limits were 0.001 9，0.004 1，0.003 7， 0.006 2，0.003 5，0.002 9，0.001 5 mg/mL；RSDs for precision ，stability（24 h），and repeatability tests were all less than 2％ （n＝5 or n＝6）； the average recoveries were 98.48％ ， 014） 101.37％，97.96％，99.80％，102.79％，97.77％，102.14％， and RSDs were all lower than 2％（n＝9），respectively. The average relative correction factors of α-cyperone，α-pinene， β-pinene，β-elemene，caryophyllene oxide and ligustilide were 1.045 8，0.621 0，0.488 5，0.382 9，0.708 9，0.956 9 respectively，and the RSDs were all lower than 2％（n＝6）. There wa s no statistical significance in contents of 7 components between QAMS method and internal standard method （P＞0.05）. CONCLUSIONS ：The established QAMS method is simple ， accurate，stable and reproducible ，and can be used for simultaneous determination for 7 components in Yueli yaomi spray.  
        关键词：QAMS;Yao medicine;Yueli yaomi spray;GC;Quality control   
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        发布时间：2022-06-21
      • CUI Yuanyuan,ZHOU Yongfeng,MA Yanqin,FANG Jixiang,WANG Guoqiang,ZHANG Rongrong,DONG Yi,ZHANG Ping
        Vol. 31, Issue 9, (2020)
        摘要：OBJECTIVE：To compare the che mical composition differences of raw and fried processed Glycyrrhiza uralensis ， and provide reference for clarifying the regularity of chemical composition change before and after processing and material basis of differential use of raw and fried G. uralensis . METHODS ：UPLC-Q-TOF-MS technology was used to detect the composition of raw and fried G. uralensis . By comparing the retention time ，relative molecular weight and other information of the compounds with the databases such as METLIN ，Agilent MassHunter PCDL Manager off-line component identification workstation and references ，the chemical compositions of the compounds were preliminarily identified. Principal component analysis （PCA）method was used to observe the overall distribution trend of samples. Orthogonal partial least square （OPLS-DA）method was used to screen differential compounds [VIP ＞1.0 and | P（corr）|≥0.5 as criteria] and analyze the content changes of differential compounds. RESULTS ：A total of 31 common compounds were preliminarily identified from the raw and fried G. uralensis . PCA analysis showed that raw and fried G. uralensis could be separated well. OPLS-DA analysis result showed that 15 characteristic differential compounds were screened out from raw and fried G. uralensis ，including 13 flavonoids and 2 coumarins；the contents of 8 flavonoids compounds such as licoflavone A ，glycyrrhizin and glabridin and so on in G. uralensis were significantly increased （P＜0.05 or P＜0.01）， while the contents of 5 flavonoids components such as glycyrrhizinol ，glycyrin A and 2 coumarins components such as 2′-4′-trihydroxy-5-methoxy-3-coumarim and hedysarimcoumestan B were significantly decreased （P＜0.05） after honey-fried processing. CONCLUSIONS ：Before and after processing ，there are obvious differences between some flavonoids and coumarins ， which may be the main material basis for differential use of raw and honey-fried G. uralensis .  
          
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        发布时间：2022-06-21
      • WANG Yun,LI Pingping,GAO Zhenshen,ZHANG Xiaoping,WANG Zhen,ZHOU Hong
        Vol. 31, Issue 9, (2020)
        摘要：OBJECTIVE：To prepare Cheler ythrine （CHE） solid dispe rsion （SD），optimize the formulation technology ， characterize its preparation and investigate its in vitro antioxidant activity. METHODS ：The content of CHE in SD was determined by UV spectrophotometry. Based on single factor tests ，using the product yield as index ，using preparation method ，carrier material type，carrier material proportion （drug-carrier material mass ratio ）as factors ，the formulation technology of SD was optimized by L（9 34）orthogonal test and validated. Based on solubility and accumulative dissolution determination ，the product was characterized with thermal analyssis ，X-ray diffraction and scanning electron microscope. Using ascorbic acid as positive control ，in vitro antioxidant activity of the product was determined by DPPH method. RESULTS ：The linear range of CHE was 2.4-5.6 μg/mL； quantitation limit and detection limit were 0.066 9，0.022 1 μg/mL；RSDs of precision ，stability and reproducibility tests were all lower than 2％；recoveries were 97.50％-99.25％（RSD＜1％， n＝3）. The optimal preparation technology included using PEG 6000 as carrier material ，carrier material ratio of 1 ∶ 3， prepared by solvent method. Three batches of CHE-PEG-SD were prepared. Verification test results showed that the 话：0539-80311889。E-mail：zhenshengao@163.com accumulative dissolution of CHE-PEG-SD was （61.72 ± 0.67）％ at 15 min，and the yield was （99.04±0.83）％. The results of characterization showed that after CHE-PEG-SD prepared ， its solubility （3.725 mg/mL）and accumulative dissolution （61.25％，15 min）were higher than CHE raw material [ 0.098 mg/mL， 6.24％（180 min）]. The endothermic peak and crystal absorption peak moved or even disappeared compared with raw material and the carrier material ，and CHE was uniformly dispersed in the carrier material as an amorphous state. Results of in vitro antioxidation test showed that different concentration of CHE-PEG-SD showed certain ability of DPPH free radical scavenging ，and the IC 50 was 0.124 mg/mL，higher than 0.041 mg/mL of ascorbic acid. CONCLUSIONS ：Established content determination method is simple and accurate. The optimal SD formulation technology is stable and feasible. The solubility of prepared CHE-PEG-SD increases，and the dissolution in vitro increases，showing certain in vitro oxidation resistance.  
        关键词：Chelerythrine;Solid dispersion;Technology optimization;Dissolution in vitro;Characterization;Antioxidant   
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        发布时间：2022-06-21
      • DING Jie,YAN Guangling,YANG Pei,ZHANG Yongqing,LIU Yuhong
        Vol. 31, Issue 9, (2020)
        摘要：OBJECTIVE：To establis h the fingerprint of Lonicera japonica polysaccharide，and to investigate in vitro inhibitory effect of it on respiratory syndrome virus （RSV）. METHODS ：Polysaccharide from L. japonica was prepared by water extraction and twice alcohol precipitation method. After hydrolysis with trifluoroacetic acid ，derivatization with hydroxylamine hydrochloride and pyridine ，the fingerprint was established by GC method. The determination was performed on HP- 5 capillary column ，and the detector was flame ionization detector ；the temperature of the sample inlet was 250 ℃；the temperature of the detector was 300 ℃ （programmed temperature ）；the carrier gas was nitrogen （flow rate of 50 mL/min）；split sampling was adopted （split ratio of 60∶1）；the sample size was 2.0 μL. Using rhamnose as reference substance，GC fingerprint of 12 batches of L. japonica （S1-S12） was drawn ，and the similarity evaluation was performed with Similarity Evaluation System of TCM Fingerprint （2012 edition）. Cluster analysis and principal component analysis were conducted by using SPSS 21.0 software. Using ribavirin as positive control ， half effective concentration （EC50）and treatment index （TI）as indexes ，MTT assay was used to investigate in vitro inhibitory effect of L. japonica polysaccharide on RSV. RESULTS ：There were 12 common peaks in GC fingerprint of 12 batches of L. japonica. The similarity was greater than or equal to 0.994. Seven common peaks were identified ，such as rhamnose ，arabinose， fucose，mannose，glucose，galactose，inositol hexaacetate. According to the cluster analysis ，12 batches of samples could be divided into two categories ，i.e. S 1，S7，S10 and S 11 clustered into one category ，and others clustered into one category. In principal component analysis ，the eigen values of 3 principal components were all greater than 1 （5.659，2.745，1.724 respectively），and their cumulative contribution rate was 84.400％. The comprehensive score of S 12 was the highest ，the second was S 5，and the lowest was S 11. EC 50 of total polysaccharide ，80％ alcohol precipitated polysaccharide ，50％ alcohol precipitated polysaccharide and 20％ alcohol precipitated polysaccharide of L. japonica （No. S 12） were 0.76，0.61，1.03，3.04 g/L， respectively；TI were 15.36，18.51，11.69，4.22，respectively. EC 50 of 80％ ethanol alcohol precipitated polysaccharide was the lowest，and its TI was close to that of positive control （20.08）. CONCLUSIONS ：Established fingerprint provides reference for the quality evaluation of L. japonica . L. japonica polysaccharide has a certain inhibitory activity on RSV in vitro ，and the 80％ alcohol precipitated polysaccharide has the strongest activity.  
        关键词：Lonicera japonica polysaccharide;Fingerprint;Gas chromatography;Principal component analysis;Antivirus   
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        发布时间：2022-06-21
      • JIN Jingmei,YU Dayong,HOU Tao,ZHANG Xiuli,SHI Liying
        Vol. 31, Issue 9, (2020)
        摘要：OBJECTIVE：To provide reference for elucidating the anti-allergic asthma constituents in alkaloids-free part of Ephedrae Herba. METHODS ：Ephedrae Herba was extracted with 85％ ethanol and n-heptane，and then subjected to solid-phase extraction（filler AC 18）for pretreatment to enrich alkaloids-free part from the extract of Ephedrae Herba. HPLC method was adopted，and alkaloids-free fractions of Ephedrae Herba were performed on Unitary C 18 column and Eclipse XDB-C 18 column. Using high expression G protein coupled-receptor 35（GPR35 receptor）in HT- 29 cell as target ，GPR35 receptor agonist zaprinast （1 μmol/L）as positive control ，DMR response value as the detection index ，the agonistic and desensitizing activity of each fraction（100 μg/mL）on GPR 35 receptor was screened by label-free integrated pharmacological method ，so as to screen active anti-allergic asthma fraction. HPLC-Q-TOF-MS method was used to identify the chemical composition of the selected active fractions. RESULTS ：The alkaloids-free part of Ephedrae Herba was divided into two parts ，involving the precipitated part before solid phase extraction and the 95％ methanol elution part ；from them ，20 fractions were screened. Among them ，the precipitated fraction F 1.5-F1.10 and 95％ methanol eluted fraction F 2.5-F2.10 had a strong agonistic activity on GPR 35 receptor；at the same time，GPR35 receptor agonist zaprinast showed a relatively strong desensitization activity. The signal intensity of DMR induced by F1.5-F1.10 in the precipitated part of HT- 29 cells was even higher than that of reference drug zaprinast. By HPLC-Q-TOF-MS analysis，24 chemical components were identified from active fractions ，involving 14 flavonoids，2 volatile oils ，7 organic carboxylic acids ，1 anthraquinones. CONCLUSIONS ：The alkaloid-free part of Ephedrae Herba is mainly flavonoids and has anti-allergic asthma activity.  
          
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        发布时间：2022-06-21
      • CUI Xuehui,CHEN Shihong,QIU Jindi,BAN Junfeng,YANG Nannan,NI Qingchun,PAN Zhaoyan,XIE Qingchun,CHEN Yanzhong,LYU Zhufen
        Vol. 31, Issue 9, (2020)
        摘要：OBJECTIVE：To prepare Imperatorin ultradeformable liposomes gel （IMP-UDLs-Gel），and to evaluate its quality. METHODS：Based on single factor test ，using 12 h accumulative penetration amount （Q12h）as evaluation index ，the proportion of carbomer 940，glycerol and propyl glycol in formulation of IMP-UDLs-Gel were investigated by orthogonal test. The optimal formulation was screened. The quality of IMP-UDLs-Gel prepared with the optimal formulation was evaluated. RESULTS ：The optimal formulation of IMP-UDLs-Gel included carbomer 940 proportion of 1％，glycerol proportion of 15％ and propyl glycol proportion of 10％. Q12 h of IMP-UDLs-Gel was （11.543±0.241）μg/cm2；the appearance was milky white and translucent ；the particle size was （93.13±1.68）nm，PDI was 0.268±0.012，Zeta potential was （－24.96±1.99）mV；pH was 7.32±0.03； viscosity was （45.37±1.27）g·s；steady flow was （0.727±0.002）μg·h/cm2，lag time was （4.358±0.175）h，apparent permeability coefficient was 1.392×10－3 cm/h，and it has good physical and optical stability. CONCLUSIONS ：The preparation method is stable and feasible ，and the prepared IMP-UDLs-Gel has good adhesion ，stability and transdermal property.  
          
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        发布时间：2022-06-21
      • LAI Zhengquan,AI Weipeng,HU Zhen,DOU Yaoxing,CAI Yufeng,LIU Wei,WU Ying,ZHANG Citing,XIE Xiaolin,LIAO Huijun
        Vol. 31, Issue 9, (2020)
        摘要：OBJECTIVE：To provide reference for improving the quality sta ndard of Equisetum hyemale . METHODS ：Totally 10 batches of E. hyemale from different sites were collected as samples. TLC method was used to qualitatively identify kaempferol- 3-O-β-sophoroside. The contents of heavy metal ，aflatoxin，impurity，moisture，total ash ，acid-insoluble ash ，water-soluble extract and ethanol-soluble extract were determined according to supplementary provisions of Chinese Pharmacopoeia （2015 edition）. HPLC method was used to determine the content of kaempferol- 3-O-β-sophoroside in sample. HPLC fingerprint of water-soluble extract from E. hyemale was also established. RESULTS ：TLC identification showed that in the chromatogram of the test sample ， fluorescent spots with the same color were displayed on the corresponding positions of the chromatogram of substance control of kaempferol-3-O-β-sophoroside，and without interference from blank control. Among 10 batches of samples ，the contents of impurities were 0.19％-2.32％；the water contents were 10.12％-11.87％；the total ash contents were 6.67％-10.11％；the acid-insoluble ash contents were 1.34％-2.12％；the water-soluble extract contents were 9.17％-13.99％；the ethanol-soluble extract contents were 7.49％-13.68％，respectively. It is preliminarily proposed that the impurity content shall not exceed 3.00％；the total ash content shall not exceed 10.00％；the acid-insoluble ash content shall not exceed 2.50％；the water-soluble extract content shall not be less than 9.00％ ；the ethanol-soluble extract content shall not be less than 5.00％. Arsenic（0.064-0.225 mg/kg） 010815） was detected in 9 batches of samples ；cadmium（0.106-0.132 E-mail：cruise0303@163.com mg/kg）was detected in 6 batches of samples ；lead（0.221- 1.896 mg/kg）was detected in all samples ，but no mercury or rebecca aflatoxin was detected. The results of HPLC method met the relevant requirements of Chinese Pharmacopoeia . The content of kaempferol- 3-O-β-D-sophoroside in 10 batches of samples was 627.12-5 384.53 mg/kg，and the similarity of HPLC fingerprints of 10 batches of samples was more than 0.900. CONCLUSIONS ： A new qualitative and quantitative analysis method for kaempferol- 3-O-β-D-sophoroside was established ；the heavy metals ， aflatoxins，impurities and other items in E. hyemale were detected ；the limits of impurity ，ash and extract were determined. The established method is simple ，accurate and reproducible ，and can be used for quality control of E. hyemale .  
        关键词：Equisetum hyemale;Kaempferol-3-O-β-sophoroside;TLC;HPLC;Fingerprint;Quality standard   
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        发布时间：2022-06-21
      • HUANG Zhoufeng,HU Xiaoxi,HUANG Jianyou,TAN Xiao,LU Guoshou,LIANG Xinqiao
        Vol. 31, Issue 9, (2020)
        摘要：OBJECTIVE：To optimize ultrasonic-assisted ethanol-（NH4）2SO4 aqueous two-phase extraction technology of citru- sinol from Desmodium caudatum . METHODS ：Using the content of citrusinol as indexes ，with ethanol volume fraction ， solid-liquid ratio ，（NH4）2SO4 addition amount ，ultrasonic time and ultrasonic temperature as factors ，based on the single factor tests，Box-Behnken design-response surface methodology was used to optimize the extraction technology of citrusinol. RESULTS ： The optimized extraction technology of citrusinol included that ethanol volume fraction was 95.35％，the solid-liquid ratio was 1∶50.35 （g/mL），（NH4）2SO4 addition amount was 4.49 g，ultrasonic time was 48.7 min，ultrasonic temperature was 57.6 ℃. In 3 times of validation tests ，the extraction rates of citrusinol were 0.637 8，0.638 4，0.625 4 mg/g，respectively，which was close to predicted value（0.630 5 mg/g）. CONCLUSIONS ：The optimized ultrasonic-assisted ethanol- （NH4）2SO4 aqueous two-phase extraction technology is stable and feasible ，and can be used for the extraction of citrusinol from D. caudatum .  
          
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        发布时间：2022-06-21
      • WU Zhongyong,WANG Jinzhong,ZHOU Sen,LIN Ming,WANG Xiaozhi
        Vol. 31, Issue 9, (2020)
        摘要：OBJECTIVE：To explore the mec hanism of baicalein plat elet aggregation inhibitiory effect and lung tissue protective effect of baicalein in model rats with acute pulmonary embolism. METHODS ：Totally 36 rats were randomly divided into normal control group （n＝6）and modeling group （n＝30）. The acute pulmonary embolism model was established by autologous thrombus replication in modeling group ，and the sham operation of rats in normal control group was carried out. After modeling ， 30 model rats were randomly divided into model control group ，positive drug group （low molecular weight heparin calcium 0.01 mL/kg，subcutaneous injection ），baicalein low-dose ，middle-dose and high-dose groups （25，50，100 mg/kg，intraperitoneal injection），with 6 rats in each group. Normal control group and model control group were intraperitoneally injected constant volume of normal saline ；administration groups were given relevant medicine ，once a day ，for consecutive 7 d. After medication ， platelet aggregation rates of rats after activated with adenosine diphosphate （ADP） and arachidonic acid （AA） and platelet activation index （RPI）were detected ；lung histopathology was observed by HE staining ；serum platelet activation markers granule membrane（CD62P）and lysosomal membrane glycoprotein （CD63），growth differentiation factor- 15（GDF-15）and N-terminal B-type natriuretic peptide （NT-proBNP）were measured by ELISA. The mRNA expression levels of Notch 2，Notch3 and Notch signaling ligand PLL 1，JAG2 were detected by RT-PCR method. The protein expression levels of Notch 2，Notch3，DLL1 and JAG2 in lung tissue were detected by immunohistochemistry and Western blotting assay. RESULTS ：Compared with normal control group，plasma ADP-activated platelet aggregation rate ，AA-activated platelet aggregation rate ，RPI，serum levels of CD 62P， CD63，GDF-15 and NT-proBNP were increased significantly （P＜0.05）. The lung tissue of rats was in a state of severe inflammatory infiltration. mRNA and protein expression levels of Notch 2，Notch3，DLL1 and JAG 2 in lung tissue decreased significantly（P＜0.05）. Compared with model control group ，changes of above indexes of rats were improved significantly in baicalein groups （P＜0.05）. CONCLUSIONS ：Baicalein can reduce platelet aggregation and improve the pathological state of lung tissue in rats with acute pulmonary embolism. Its mechanism 0270） may be related to activating Notch signal pathway.  
          
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      • SHEN Huarui,AO Liang,WANG Lisheng,WANG Guoyou,HAO Qi,LI Ting
        Vol. 31, Issue 9, (2020)
        摘要：OBJECTIVE：To study the mechanism of enhancement effects of Astragalus complanatus polysaccharides（ACP） on the proliferation of meniscal fibrochondrocytes cells in rabbits. METHODS ：The meniscal fibrochondrocytes cells were isolated from 1-month-old New Zealand white rabbits. The meniscal fibrochondrocytes cells were divided into normal control group （PBS）， positive control group （glucosamine sulfate ，10 mg/mL）and ACP high-dose，medium-dose and low-dose groups （40，20，10 mg/mL）. The morphology of meniscal fibrochondrocytes cells were observed under microscope. Cell proliferation rate was detected by MTT assay. Cell cycle was observed with flow cytometry. ELISA assay was used to detect relative expression of medium collagen type Ⅱ（Col Ⅱ）and alkaline phosphatase protein （ALP）in meniscal fibrochondrocytes cells. RT-qPCR and Western blotting assay were adopted to detect mRNA and protein expression of transforming growth factor β 1 （TGF-β 1） and bone morphogenetic protein 2（BMP-2）. RESULTS ：After cultured for 72 h，meniscal fibrochondrocytes cells were fused into a single layer，and most of them were slender type in appearance. Compared with normal control group ，the proliferation rate of meniscal fibrochondrocytes cells and the percentage of cells at G 1/G0 phase were decreased significantly in positive control group and ACP high-dose，medium-dose and low-dose groups （P＜0.05）；the percentage of cells at S phase ，protein expression of Col Ⅱ and ALP，mRNA and protein expression of TGF-β1 and BMP- 2 were increased significantly （P＜0.05）. Compared with positive control group，inhibitory rate of meniscal fibrochondrocytes cells proliferation and the percentage of cells at G 1/G0 phase were decreased significantly in ACP high-dose group （P＜0.05），while the percentage of cells at S phase ，protein expression of Col Ⅱ and ALP ， mRNA and protein expression of TGF-β1 and BMP- 2 were increased significantly （P＜0.05）. The inhibitory proliferation rate of meniscal fibrochondrocytes cells and the percentage of cells at G 1/G0 phase were increased significantly in ACP low-dose group （P＜ 0.05），while the percentage of cells at S phase ，protein expression of Col Ⅱ and ALP ，mRNA and protein expression of TGF-β1 and BMP- 2 were decreased significantly （P＜0.05）. There was no statistical significance in above indexes of ACP medium-dose group. CONCLUSIONS ：ACP can promote the proliferation of meniscal fibrochondrocytes cells ，reduce the percentage of cells at G1/G0 phase，promote cell transformation to S phase ；the mechanism of which may be related to up-regulating TGF-β1，BMP-2 mRNA and protein expression ，promoting Col Ⅱ and ALP protein expression enhancement.  
          
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      • LI Hanyang,QIU Zhidong,SU Wenlong,CAO Wenzheng,LI Xintong,JIANG Changpeng,GAO Hongmei
        Vol. 31, Issue 9, (2020)
        摘要：OBJECTIVE：To investigate t he effects of different compatibility ratio of Gardenia jasminoides to fermented soybean on the content of genistein and total flavonoids ，and to investigate the compatibility regularity of Zhizichi decoction. METHODS：The decoction method was used to prepare the mixed decoction with different compatibility ratio of G. jasminoides to fermented soybean （2∶1，1∶1，1∶2，1∶4，m/m，the same hereinafter ）. UPLC-MS/MS method was used to determine the content of genistein in Zhizichi decoction with different compatibility ratio and corresponding fermented soybean single decoction. UV method was used to determine the content of total flavonoids in Zhizichi decoction with different compatibility ratio and corresponding gardenia single decoction and fermented soybean single decoction. RESULTS ：The established method had good linearity ， precision，repeatability，stability and accuracy. Compared with single decoction ，the content of genistein in the mixed decoction with different compatibility ratio of G. jasminoides to fermented soybean （2∶1，1∶1，1∶2，1∶4）was decreased to different extents ， while the content of total flavonoids was increased to different extents. With the increase of fermented soybean ，the content of genistein in the decoction increased at first and then decreased. When the compatibility ratios of G. jasminoides to fermented soybean were 1 ∶ 1 and 1 ∶ 2，the content of genistein in the decoction was the highest （all 0.071 μg/mL）. With the increase of fermented soybean ，the content of total flavonoids in the decoction did not change regularly ；when the ratio of G. jasminoides to fermented soybean was 1 ∶ 1，the content of total flavonoids in the decoction was the highest （1.861 μg/mL）. CONCLUSIONS ： When the compatibility ratio of G. jasminoides to fermented soybean was 1 ∶ 1，the content of flavonoids in the decoction is the highest.  
        关键词：Zhizichi decoction;Fermented soybean;Compatibility regularity;Genistein;Total flavonoids;Content   
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      • XUE Qiaoru,YUAN Jinye,DING Liuyang,ZHENG Weijun,DENG Feng
        Vol. 31, Issue 9, (2020)
        摘要：OBJECTIVE：To establish UPLC method for the content determination of related substances in Terlipressin for injection. METHODS ：UPLC method was used to determine the contents of related substances in 5 batches of Terlipressin for injection. The separation was performed on Xtimate UPLC C 18 column with mobile phase A consisted of ammonium sulfate buffer （pH 2.3）-methanol（90 ∶ 10，V/V）and mobile phase B consisted of ammonium sulfate buffer （pH 2.3）-methanol（60 ∶ 40，V/V） （gradient elution ）at the flow rate of 0.2 mL/min. The detection wavelength was set at 210 nm，and sample size was 5 μL. RESULTS：The linear range of impurity A ，B，C，D，F，H，I，K，L and N were 0.43-3.86，0.44-3.95，0.44-3.97，0.45-4.08， 0.45-4.05，0.50-4.50，0.47-4.26，0.47-4.23，0.46-4.13，0.44-3.96 μg/mL（r≥0.999 7），respectively. The detection limits were 0.04， 0.04，0.05，0.04，0.05，0.05，0.05，0.05，0.04 μg/mL. The quantitation limits were 0.13，0.13，0.14，0.13，0.15，0.14，0.14， 0.14，0.13 μg/mL，respectively. RSDs of precision ，reproducibility and stability tests were all lower than 8％. The average recoveries were 94.95％，97.81％，101.88％，95.26％，93.40％，102.48％，104.26％，102.31％，96.42％，90.42％，with RSD s of 1.89％，1.86％，0.68％，1.30％，1.98％，3.36％，1.26％，1.30％，1.19％，1.40％（n＝9），respectively. Total contents of impurities in 5 batches of Terlipressin for injection were all lower than 4％. CONCLUSIONS ：Established method is rapid ，simple， accurate and specific ，which can be used for the quantitative analysis for related substances in Terlipressin for injection.  
        关键词：UPLC;Terlipressin for injection;Related substance;Content determination   
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      • CHEN Chen,AI Dandan,LU Yun
        Vol. 31, Issue 9, (2020)
        摘要：OBJECTIVE：To evalua te the economics of glecaprevir/pibrentasvir （G/P）versus elbasvir/grazoprevir （EBR/GZR） in chronic hepatitis C genotype 1b（GT1b）treatment-naive patients without cirrhosis ，and to provide evidence support for medical and health decision-making. METHODS ：Under assuming the bid price of G/P and EBR/GZR therapy schemes before medical insurance negotiation was adopted （scenario 1）and assuming that the price of EBR/GZR was reduced by 85％ and the price of G/P was reduced by 80％（scenario 2），Markov model was developed to simulate the lifetime cost and health outcomes progress of 10 000 untreated chronic hepatitis C GT 1b treatment-naive patients without cirrhosis and calculate incremental cost-effectiveness ratio（ICER）. Single factor sensitivity analysis and probability sensitivity analysis were conducted to verify the results. The highest price（price reduction ratio ）of G/P scheme was analyzed with cost-effectiveness advantage ，when other parametes kept stable under scenario 2. RESULTS ：Under 2 kinds of scenarios ，compared with EBR/GZR scheme ，G/P scheme had higher cost （scenario 1：68 800 yuan vs. 62 338 yuan；scenario 2：13 760 yuan vs. 11 490 yuan）and healty utility （scenario 1：14.97 QALY vs. 14.90 QALY；scenario 2：14.97 QALY vs. 14.90 QALY），and ICER value of G/P was lower than willingness-to-pay threshold （scenario 1：92 314 yuan/QALY；scenario 2：32 428 yuan/QALY）. The change of most parameters in single factor sensitivity analysis didn ’t influence the results of base-case analysis ，and the findings from the base-case analysis were confirmed by probability sensitivity analyses. The price of G/P scheme needed to be reduced by at least 62％ to realize cost-effective advantage. CONCLUSIONS ： Under the set price scenario ，G/P scheme has cost-effectiveness advantages than EBR/GZR scheme in chronic hepatitis C GT 1b treatment-naive patients without cirrhosis.  
        关键词：Chronic hepatitis C;Markov model;Cost-effectiveness analysis;Glecaprevir/pibrentasvir;Elbasvir/grazoprevir   
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      • LIU Hailin,YUAN Hongmei,WANG Hu,DIAO Junlin,ZHOU Chunqiao,DING Xiaoli,ZHANG Xuelin,DONG Zhi,WANG Song
        Vol. 31, Issue 9, (2020)
        摘要：OBJECTIVE：To excavate the safety warning signals induced by azole antifungal agents ，including fluconazole ， ketoconazole，itraconazole and voriconazole after marketing ，and to provide references for rational drug use in the clinic. METHODS：Reporting odds ratio （ROR）data mining algorithm was used to investigate signals of adverse drug event （ADE）for fluconazole，ketoconazole，itraconazole and voriconazole from FDA Adverse Event Reporting System （FAERS）during January 1st，2004 to March 30th，2019. ROR data mining method was used to excavate the ADR signals of the drugs ，and main ADR involved in the safety information of azole antifungal agents instructions were analyzed. RESULTS ：A total of 27 831，5 712， 5 381 and 11 333 reports were picked out for fluconazole ，ketoconazole，itraconazole and voriconazole ，respectively. All of these drugs had exhibited high-risk signals detection by ROR ，including medical examination ，blood and lymphatic system disorders ， renal and urinary disorders ，endocrine diseases ，hepatobiliary disorders. The hepatotoxic-related ADR signals were mainly concentrated in fluconazole and voriconazole （fluconazole ROR ＝6.51，voriconazole ROR ＝14.65）；ADR detection results of Cushing’s-like syndrome （ROR＝24.86） and adrenal suppression （ROR＝44.06） by itraconazole showed high-risk signals ； ketoconazole and itraconazole had showed a strong ADR signal in adrenocortical dysfunction （ketoconazole ROR ＝15.64， itraconazole ROR ＝23.26），and the signal intensity of ketoconazole （ROR＝2.81）in skin and subcutaneous tissue disorders was significantly higher than that of other drugs . In addition ，hemorrhagic cystitis caused by fluconazole，itraconazole and voriconazole were not included in the drug instructions （fluconazole ROR ＝17.73，itraconazole ROR ＝31.43，voriconazole ROR ＝17.06）； netted green spot caused by fluconazole （ROR＝10.50）were not included in the drug instructions . CONCLUSIONS：Clinical staff should pay more attention to the differences in serious ADR related to fluconazole ，ketoconazole，itraconazole and voriconazole ； particularly some ADRs not mentioned in the drug instructions but have high incidence such as hemorrhagic cystitis caused by fluconazole，itraconazole，voriconazole and netted green spot caused by fluconazole ，as well as ADRs mentioned in the drug instructions but have abnormally high signal ，such as Cushing ’s-like syndrome and adrenal suppression caused by itraconazole .  
        关键词：Fluconazole;Ketoconazole;Itraconazole;Voriconazole;ADR;Signal mining;Reporting odds ratio   
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      • CHEN Zhe,LIN Mao,ZENG Linan,HUANG Liang,YU Dan,ZHANG Lingli
        Vol. 31, Issue 9, (2020)
        摘要：OBJECTIVE：To systematically evaluate the safety of Chloral hydr ate（CH）oral solution for sedative and hypnotic in children，and to provide evidence-based reference for clinical use. METHODS ：Retrieved from 9 electronic databases （PubMed， Cochrane Library ，Embase，CINAHL，International Pharmaceuticals ，CNKI，CBM，Wanfang Database ，VIP），3 clinical trial registry platforms （Clinical Trials ，Cochrane Clinical Trial Database ，WHO Clinical Trial Database ）and 18 adverse drug reaction （ADR）monitoring systems （ADR monitoring websites of WHO ，USA，Switzerland，China and other countries/areas/international organizations），during the date of database establishment to March 2019，the reports of randomized controlled trials ，cohort studies，case-control studies ，case series studies ，case reports ， cross-sectional studies and adverse reactions monitoring network of chloral hydrate versus other interventions （blank 85503205。E-mail：chenzhehx@163.com control，placebo or other sedative hypnotics ）for children ’s sedative and hypnotic safety were collected. After data extraction of included literatures met inclusion criteria ，quality mail：zhanglingli@scu.edu.cn evaluation of included s tudies with Cochrane bias risk evaluation manual （RCT），Newcastle-Ottawa scale evaluation tool （Cohort study and case control study ），Australian JBI quality assessment tool （case series study and case report study ），Meta-analysis was performed by Rev Man 5.3 software，or descriptive analysis was conducted. RESULTS ：A total of 54 studies were included ，among which there were 13 RCTs，9 cohort studies ，17 case series studies ，13 case reports ，and 2 reports from ADR monitoring network. Based on the results of RCT and cohort studies ， the incidence of Chloral hydrate oral solution adverse events was 7.25％. There was no statistical significance in the incidence of digestive system [RR ＝0.87，95％ CI（0.14，5.42），P＝0.88]，nervous system [RR ＝0.13，95％ CI（0.01，2.41），P＝0.17]， cardiovascular system [RR ＝2.12，95％ CI（0.08，56.57），P＝0.65] adverse event between Chloral hydrate oral solution and midazolam. The incidence of respiratory system adverse events induced by Chloral hydrate oral solution was higher than that of midazolam [RR ＝3.07，95％CI（1.94，4.86），P＜0.01]. There was no statistical significance in the incidence of digestive system adverse events between Chloral hydrate oral solution and diazepam [RR ＝0.71，95％CI（0.47，1.10），P＝0.13]. There was no statistical significance in the incidence of digestive system ，nervous system and cardiovascular system adverse events between Chloral hydrate oral solution and barbiturates （P＞0.05）. CONCLUSIONS ：Chloral hydrate oral solution is similar to midazolam ， diazepam and barbiturates in terms of digestive ，nervous and cardiovascular systems adverse events ，but the incidence of respiratory system adverse events is higher than midazolam.  
        关键词：Chloral hydrate;Oral solution;Child;Sedative and hypnotic;Safety;Systematic review   
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      • WANG Zheyuan,LUO Xin,YE Zhen,YE Xuan,YU Bo,ZHAI Qing,DU Qiong
        Vol. 31, Issue 9, (2020)
        摘要：OBJECTIVE：To investigate antitumor pharmaceutical care ability a nd the current status of direct to patient （DTP） pharmacy in China ，and to provide reference for building a quality evaluation system of DTP pharmacy which focuses on the pharmaceutical care. METHODS ：From Sept. to Dec. 2019， an electronic questionnaire survey was conducted amongpharmacists of all of 126 listed DTP pharmacies and involved wang_star@163.com education background ，professional knowledge sources andpharmaceutical care ability （such as prescription checking and E-mail：dujoan-88@163.com dispensing，medication consultation and guidance ，medication management，follow-up），pharmaceutical knowledge of antitumor medicine ，etc. DTP pharmacies in C hina were inspected on site ， and their pharmaceutical care management were evaluated ，and impression of on-site inspection were discribed with questionnaire survey. The current situation of oncology pharmaceutical care ability of DTP pharmacy in China was evaluated and corresponding suggestions were put forward. RESULTS ：A total of 400 questionnaires were sent out ，and 392 valid questionnaires were collected with recovery rate of 98.0％. The cancer pharmacists in DTP pharmacy were mainly from East China ，mainly in Jiangxi （73 persons，18.62％），Anhui（68 persons，17.35％）. The pharmacists were mainly junior college or below （229 persons，58.42％）， followed by undergraduate （158 persons，40.31％）. The working years were more than 5 years（241 persons，61.48％）. The majors were mostly pharmaceutics （123 persons，31.38％），followed by pharmacy （including pharmacology ）（81 persons， 20.66％）. The regular knowledge sources of pharmacists in DTP pharmacy included learning materials （302 person times ， 77.04％），textbooks（250 person times ，63.78％）and Wechat push （206 person times ，52.55％）；the latest knowledge sources included training courses （347 person times ，88.52％），Wechat push （211 person times ，56.38％）and academic conferences （162 person times ，41.33％）. The expected training methods included online video courses （344 person times ，87.76％）and offline courses（248 person times ，63.27％）. In terms of prescription checking and dispensing ，there were mainly problems such as incomplete medical documents and materials ；82.91％ and 64.54％ of pharmacists needed routine medical records and discharge summary，and 91.58％ of pharmacists took the doctor ’s handwritten prescription as the basis for dispensing new anti-tumor drugs ； pharmacists paid less attention to allergy history ，genetic history and ADR in the field of drug consultation and guidance. According to DTP pharmacists ，the difficulties in the process of drug treatment management included patient ’s ADR monitoring （239 person times，60.97％），evaluating the rationality of drug use （222 person times ，56.63％），making a complete drug use record （219 person times ，55.87％）. The main follow-up visits of pharmacists were telephone （334 person times ，85.20％）and dispensing site （313 person times ，79.85％）. And 333 pharmacists（84.95％）thought it was necessary to make an appointment for dispensing ；the score rates of professional knowledge examination of antitumor pharmacy for the respondents were 40.56％-84.69％. In the aspect of pharmaceutical care management ，the main points of deduction were drug evaluation ，content and process of drug treatment management，drug follow-up and record ，and the proportion of deduction was 93％，86％ and 64％ respectively. In the on-site inspection，it was found that the pharmacist had a single source of working knowledge ，did not fully grasp the contents of the evaluation forms such as ADR classification standard ，and prescription checking did not meet the requirements. CONCLUSIONS ： DTP pharmacy in China develops rapidly under the guidance of relevant policies ，but its pharmaceutical care is still in the basic stage，which is far behind the requirements of providing whole-course pharmaceutical care for patients. It is necessary to improve the professional service ability of DTP pharma  
        关键词：DTP pharmacy;Questionnaire;On-site inspection;Pharmaceutical care ability   
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