最新刊期
      卷 31 ， 期 21 ， 2020
      • ZHANG Yajuan,FANG Laiying
        Vol. 31, Issue 21, (2020)
        摘要：OBJECTIVE：To put forward policy suggestions for the adjustment and reform of centralized drug procurement mode in China. METHODS ：The evolution process of centralized drug procurement mode in China was reviewed ，and problems were found through literature research and expert interview. Combined with the experience of drug procurement platform construction，GPO procurement and medical insurance payment control fee management in the United States and Singapore ，the reform suggestions were put forward for basic model assumption of bidding procurement based on cost control target and drug bidding procurement policy. RESULTS & CONCLUSIONS ：China’s drug bidding procurement system has gone through the stages of unified purchase and marketing ，decentralized procurement ，centralized procurement start-up and adjustment ，comprehensive implementation of online centralized drug procurement ，exploration of the integration of “two bidding ”（bidding for essential medicine and bidding for non-essential medicine ）and joint procurement ，and pilot stage of national drug bidding and procurement. At the present stage ，there are many problems in centralized drug procurement ，such as the diversified subordination relationship of the platform ，the possible monopoly of enterprise selection under the policy of “two invoice system ”，price reduction becoming the core performance index of bidding procurement ，and the suspected monopoly operation of GPO procurement exploration. The model analysis based on the goal of cost control shows that drug cost is a function of efficiency ，drug quantity and price. High price leads to high cost ，while low efficiency leads to high cost. In the future ，the goal of drug bidding and procurement should not only foucs on price control ，but also on efficiency. The function of bidding and procurement will return to the essential function of “price for quantity ”. It is suggested that a relatively independent and unified platform should be established for drug bidding and procurement in China ，and the grouped procurement mode should be gradually standardized ，the expenditure control function of medical insurance payment audit should be exerted instead of simple price reduction ，and absolute unified lowest price procurement should be avoided.  
          
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        发布时间：2022-06-21
      • WANG Minjiao,LI Can,DU Yi,LIU Pengcheng,CAO Chunye,CAO Yang
        Vol. 31, Issue 21, (2020)
        摘要：OBJECTIVE：To construc t the evaluation system of the research quality of medical insurance budget impact analysis （BIA），and to provide feasible evaluation tool for related departments as medical insurance department. METHODS ：Based on BIA guidance documents and relevant empirical literatures of ISPOR ，Canada，Poland，the United States and other countries ， combined with expert interview ，the relevant elements of medical insurance negotiation BIA material were confirmed （including key elements and adjuctive elements ）. The scale and system was established to calculate total score of BIA research quality evaluation. RESULTS ：Key elements included three data blocks as target population ，market situation and treatment cost ，involving 14 key elements such as total population ，new drug scenario market share ，treatment cost ，etc.. According to the degree of compliance，0-3 points were assigned and the lowest score after normalization was taken as the basic score of BIA research quality. The adjunctive elements included five data blocks as title & abstract ，research background ，analysis framework ，result presentation and other ，including 23 adjunctive elements such as title ，abstract，research angle ，research time limit ，etc.. According to whether there is quality grade difference ，the elements were divided into type A and type B ；the grade score （0-4 points）and 0/1 score（1 point for yes and 0 point for no ）were used respectively ，and the additional score of BIA research quality was obtained after calculation and addition. According to the addition of different weights （0.67 and 0.33）of basic score and additional score ，the total score system of BIA research quality evaluation could be calculated. CONCLUSIONS ：This study successfully constructed a new BIA quality evaluation system ，which can be used for the quality evaluation of BIA research submitted by medical insurance drug negotiation.  
        关键词：Medical insurance;Budget impact analysis;Evaluation system;Key element;Adjunctive element   
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        发布时间：2022-06-21
      • GONG Qinqin,WANG Qian,GUO Ling,XU Jian,ZHANG Yongping
        Vol. 31, Issue 21, (2020)
        摘要：OBJECTIVE：To prepar e Celastrol oral u lcer film ，and to evalute its quality primarily. METHODS ：The comprehensive scores of the appearance ，film formation and toughness of the drug film were used as indicators ，and the amount of celastrol was controlled to 0.05％. Orthogonal test was used to optimize the amount of excipients as starch ，sodium carboxymethyl cellulose，glycerol and condensed honey ，so as to optimize the formulation ；the validation test was performed. The adhesion force of the film prepared by the optimal formulation were determined. UV spectrophotometer was used to detect the content of celastrol in the film. RESULTS ：The optimal dosage of each excipient in Celastrol oral ulcer film was starch 1.0 g，sodium carboxymethyl cellulose 0.2 g，glycerin 0.4 g，condensed honey 1.5 g. In 3 times of validation tests ，the appearance of the prepared film was good. The average adhesion of the film prepared by the optimal formulation was 4.2 g，and the average content of celastrol was 0.135 3 mg/cm2（RSD＝1.90％，n＝3）. CONCLUSIONS ：In this study ，the best formulation of Celastrol oral ulcer film was optimized，and the film forming ability of the prepared film is good and the quality is stable and uniform.  
        关键词：Celastrol;Oral ulcer;Film;Quality evaluation   
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        发布时间：2022-06-21
      • YAO Xuemin,JING Ming,CAI Fuyi,KONG Liang,LI Xuetao
        Vol. 31, Issue 21, (2020)
        摘要：OBJECTIVE：To prepare GGPFV-modified Daunorubicin/dioscin liposomes ，and to optimize their formulation and to preliminarily evaluate their cytotoxicity to breast cancer cells in vitro . METHODS ：Daunorubicin and diosgenin were wrapped by thin film dispersion method and ammonium sulfate hydration method ；the surface was modified with DSPE-PEG2000-GGPFV to prepare GGPFV-modified Daunorubicin/dioscin liposomes. Taking encapsulation rate as index ，Box-Behnken response surface methodology was used to optimize the film hydration volume ，cholesterol amount and daunorubicin amount in the formulation. The entrapment efficiency of 3 batches of liposomes prepared according to the optimal formulation was determined. The effects of Daunorubicin/dioscin liposomes ，GGPFV-modified Daunorubicin/dioscin liposomes and blank liposomes on the survival rate of human breast cancer MDA-MB- 435S cells were compared. RESULTS ：The optimal formulation was as film hydration volume of 5 mL，cholesterol of 4 mg，yolk lecithin of 22 mg，daunorubicin of 0.55 mg，dioscin of 0.85 mg，DSPE-PEG2000 of 3.5 mg， DSPE-PEG2000-GGPFV of 2 mg. The encapsulation rate of daunorubicin was （96.21±1.54）％ and that of dioscin was （95.39± 2.48）％ in the 3 batches of liposomes prepared. The in vitro cytotoxicity tests showed that the inhibition effect of GGPFV-modified Daunorubicin/dioscin liposome on MDA-MB-435S cells was significantly stronger than that of Daunorubicin/dioscin liposome （P＜ 0.05）. There was no cytotoxicity in the membrane. CONCLUSIONS ：GGPFV-modified Daunorubicin/dioscin liposomes are successfully prepared ，and its inhibitory effect on human breast cancer MDA-MB- 435S cells in vitro was significantly enhanced.  
          
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        发布时间：2022-06-21
      • AI Fei,LIU Xia,LI Hui,CHU Chunwei,CHEN Xiangyun,GUO Junfeng,YANG Yi,MEI Liyan,MIAO Jifei,WEN Quan,YE Sen
        Vol. 31, Issue 21, (2020)
        摘要：OBJECTIVE：To investigate the intervention effect of Shenfu i njection（SFI）on the nuclear translocation of high mobility group box 1（HMGB1） in lipopolysaccharide （LPS）-induced RAW 264.7 cells. METHODS ： Using LPS-induced RAW264.7 cells as objects ，the histone deacetylase inhibitor RGFP 966 as positive control ，CCK-8 assay was used to screen drug dosage，and the effects of low ，medium and high doses （3，6，12 μL/mL）of SFI on HMGB 1 nuclear translocation in RAW 264.7 cells were observed by immunofluorescence method ；mRNA expression of HMGB 1 in RAW 264.7 cells were detected by real time fluorescent PCR. Western blotting assay was used to determine protein expression of HMGB 1 and Toll-like receptor 4（TLR4）；the expression of HMGB 1 were compared between nucleus and cytoplasm. The levels of HMGB 1，IL-1β and TNF-α in supernatant of cells were detected by ELISA. RESULTS ：In blank control group ，HMGB1 was mainly located in the nucleus ；after LPS induction， HMGB1 migrated from nucleus to cytoplasm. Compared with blank control group ， mRNA and protein （No.81760738） expression of HMGB 1， protein expression of TLR 4 in RAW264.7 cells as well as the levels of HMGB 1，IL-1β and TNF-α in supernatant of cells were increased significantly in LPS group （P＜0.01）. The protein expression of HMGB 1 was decreased significantly in nucleus while was in creased significantly in cytoplasm （P＜0.01）. After SFI treatment ，the nuclear translocation and secretion of HMGB 1 were inhibited in different degrees ；compared with LPS group ，mRNA and protein expression of HMGB 1 in administration groups ，protein expression of TLR 4 in RAW 264.7 cells of positive control group ，SFI medium- and high-dose groups as well as the levels of HMGB 1，IL-1β and TNF-α in supernatant of cells in administration groups were decreased significantly （P＜0.01）. In positive control group ，SFI medium- and high-dose groups ，the protein expressions of HMGB1 in nucleus were increased significantly ，while protein expressions of HMGB 1 in cytoplasm were decreased significantly （P＜0.01）. CONCLUSIONS ：SFI may inhibit the nuclear translocation and secretion of HMGB 1 in RAW 264.7 cells，thus avoiding the activation of inflammatory pathways and the production of inflammatory factors ，so as to reduce the inflammatory response induced by LPS.  
        关键词：Shenfu injection;RAW264.7 cells;HMGB1;Inflammatory factors;Nuclear translocation   
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        发布时间：2022-06-21
      • WANG Wei,LI Xuetao,KONG Liang,JIANG Shuang,LUO Yifu,WANG Xiaobo
        Vol. 31, Issue 21, (2020)
        摘要：OBJECTIVE：To prepare cell penetrating peptide PFV-modified paclitaxel （PTX）/artesunate（ART）co-loaded targeting micelles ，and to investigate in vitro anti-tumor activity. METHODS ：According to optimal technology ，PFV-modified PTX/ ART co-loaded targeting micelles were prepared by membrane hydration method ，and were characterized. Using blank micelle as blank control ，sulforhodamine B （SRB）method was used to evaluate the toxicity of PTX micelles ，ART micelles ，PTX/ART micelles and PFV-modified PTX/ART co-loaded targeting micelles to human gastric cancer BGC- 823 cells. The coumarin was used as fluorescent probe replacing PTX to prepare corresponding micelles. Then ，the uptake of BGC- 823 cells to corresponding micelles and targeting effect were observed and determined by flow cytometry and fluorescence microscope. The effects of PTX micelles ， ART micelles ，PTX/ART micelles and PFV-modified PTX/ART co-loaded targeting micelles on the invasion of BGC- 823 cells were investigated by Transwell chamber method. RESULTS ：Average particle size of PFV-modified PTX/ART co-loaded targeting micelles was （51.30±3.95）nm；PDI was 0.19±0.01，and Zeta potential was （0.21±0.02）mV. The encapsulation efficiency of PTX and ART were higher than 90％. The shape of micelles were spherical. The blank micelles had no obvious toxicity to BGC-823 cells. The IC 50 value of PTX micelles ，PTX/ART micelles and PFV-modified PTX/ART co-loaded targeting micelles to BGC-823 cells were （3.09±0.22），（1.93±0.24），（1.11±0.15）μmol/L，respectively. The distribution amount of different micelles in BGC- 823 cell nucleus in the descending order were PFV-modified coumarin/ART micelles ＞coumarin/ART micelles ＞coumarin micelles＞blank control. The order of inhibitory effect was PFV-modified PTX/ART co-loaded targeting micelles ＞PTX/ART micelles＞ART micelles ＞PTX micelles ＞blank control. CONCLUSIONS： Prepared PFV-modified PTX/ART No.81874347） co-loaded targeting micelles are in line with the quality of 1915286446@qq.com Chinese Pharmacopoeia . It shows strong cytotoxicity to BGC-823 cells，can improve the drug targeting and the cell uptake，and inhibit the inv asion and metastasis of BGC- 823 cells.  
          
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        发布时间：2022-06-21
      • LI Fangyu,QI Bin,BIAN Shuai,ZHAO Yue,LU Shuyan,WANG Jiawen,ZHAO Daqing
        Vol. 31, Issue 21, (2020)
        摘要：OBJECTIVE：To study the effects of gin seng root extract on autophagy ，proliferation and cytokine of splenic lymphocyte of mice ，and to study its mechanism. METHODS ：The splenic lymphocyte of mice were divided into blank control group，positive control group （concanavalin A ，5 μg/mL），different concentration of ginseng root extract groups （32，125，500 μg/mL，by lyophilized powder ）. After 48 h of culture with the corresponding medicine ，acridine orange staining method was used to detect autophagy of splenic lymphocyte ；CCK-8 assay was used to detect the cell proliferation ；ELISA assay was used to determine the levels of IL- 4，IL-6 and TNF-α in cell culture；Western blotting method was used to detect the expression of LC 3B and Beclin- 1，as well as the phosphorylation of AMPK ，AKT and mTOR. RESULTS ：Compared with blank control group ，32， 125，500 μg/mL ginseng root extract could increase the number of acidic autophagosomes in splenic lymphocytes of mice（P＜0.05 or P＜0.01）；125，500 μg/mL Ginseng root extract could significantly enhance the survival rate of splenic lymphocytes，the levels of IL- 4，IL-6 and TNF-α and the transformation of LC3BⅠ to LC 3BⅡ，significantly increased the protein expression of Beclin- 1， quinacrine cationic liposomes for treating non-small cell @163.com lung cancer[J]. J Drug Target ，2015，23（3）：232-243. the phosphorylation of AMPK protein ，and significantly reduced the phosphorylation level of AKT and mTOR proteins ，with statistical significance （P＜0.05 or P＜0.01）. CONCLUSIONS ：Ginseng root extract can induce autophagy of mice splenic lymphocytes，activate the activity of splenic lymphocytes ，regulate the secretion of cytokine by activating AMPK and inhibiting the activation of AKT which can inhibit the activity of mTOR ，so as to exert immune enhancement effect.  
        关键词：Ginseng root extract;Splenic lymphocytes;Autophagy;Cytokine;Immune enhancement effect   
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        发布时间：2022-06-21
      • ZHANG Yi,YANG Xinyue,QU Yong,CHEN Yunzhong
        Vol. 31, Issue 21, (2020)
        摘要：OBJECTIVE：To s tudy the protective effect of polydat in complicated with emodin on hyperuricemia （HUA）model rats，and to screen the optimal complication proportion and investigate the potential mechanism. METHODS ：SD rats were randomly divided into normal control group ，model group ，benzbromarone group （positive control ，8 mg/kg），polydatin alone group，emodin alone group and drug combination group A ，B，C，with 5 rats in each group of each dosage. Normal control group and model group were given constant volume of 0.3％ CMC-Na solution ，administration groups were given relevant medicine intragastrically. Each group was given 0.1 mL/10 g intragastrically once a day ，for consecutive 7 d. Expect for normal control group，other groups were given intraperitoneal injection of potassium oxonate 300 mg/kg 1 h before last medication to induce HUA model. One hour after last medication ，the serum contents of uric acid （UA）were determined in normal control group ，model group，benzbromarone group ，polydatin/alone group （0.625，1.25，2.5，5，10 mg/kg）and drug combination group A [the dose of polydatin+emodin were （0.625+0.625），（1.25+1.25），（2.5+ 2.5），（5 + 5），（10 + 10） mg/kg]. The effect （Fa） and combination index （CI） of above single drug groups and combination groups were calculated by the median effect principle. The dose-effect relationship curves of twocomponents alone or combination were drawn ；Fa-CI curves after simulation were als o drawn to evaluate the effect of two-drug combination. Serum contents of UA in rats were determined and Fa value was calculated in single drug groups and drug combination group B ，C [the dose of polydatin+emodin were （0.625+ 0.625），（0.625+1.25），（0.625+2.5），（0.625+5），（0.625+10）mg/kg and （0.625+0.625），（1.25+0.625），（2.5+0.625），（5+ 0.625），（10+0.625）mg/kg]. The optimal complication proportion of two drugs were screened. The serum contents of xanthine oxidase（XOD）in rats were determined in normal control group ，model group ，benzbromarone group ，polydatin/emodin alone group（10 mg/kg）and the optimal complication proportion groups. The mechanism was analyzed primarily. RESULTS ：Compared with normal control group ，the content of UA in model group was increased significantly （P＜0.01）. Compared with model group ， except for 0.625 mg/kg polydatin alone group ，the content of UA in other administration groups were decreased significantly （P＜ 0.05 or P＜0.01）. When the two drugs were used alone or in combination ，Fa value was positively correlated with drug dose （intercept＞0，correlation coefficient ＞0.9），and Fa value of the combination group was higher than that of any single drug group ； when the simulated Fa value was more than 15％，the corresponding CI value was less than 1，two-drug combination showed synergistic effect. When the complication proportion of polydatin and emodin was 1∶4，the Fa value （53.10）was similar to that of drug combination group A （53.73），and the dose of them were less [ （0.625+2.5）mg/（kg·d）vs.（2.5+2.5）mg/（kg·d）]. Compared with normal control group ，serum content of XOD in model group was increased significantly （P＜0.01）；compared with model group，serum content of XOD in administration groups were decreased significantly ，and the optimal complication proportion group was significantly lower than polydatin alone group and emodin alone group （P＜0.05 or P＜0.01）. CONCLUSIONS ：The polydatin and emodin used alone or in combination can reduce the serum content of UA in HUA model rats by inhibiting the generation of XOD. They have a certain synergistic effect ，and the optimal complication proportion is 1∶4.  
          
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        发布时间：2022-06-21
      • CHEN Hualin,XU Jun,CAI Xiaoyang,CHEN Rong,KANG Jinmei,LI Min
        Vol. 31, Issue 21, (2020)
        摘要：OBJECTIVE：To establish the quality standard of the Tibetan medicine Ma lus Fructus （known as the fruit of Ese ）， and to provide scientific reference for quality control and utilization of resource. METHODS ：The qualitative analysis of 20 batches of Malus Fructus with different producing areas and different origins was carried out by morphological observation ，microscopic and TLC identification. According to the method stated in 2015 edition of Chinese Pharmacopoeia ，water content ，total ash content and extract content were determined. HPLC method was used to determine the contents of 6 kinds of flavones （chlorogenic acid ， hyperin，isoquercitrin，quercitin，phloridzin，quercetin）in Malus Fructus. RESULTS ：The properties of this medicinal material were obovate ，spheroidal or oval ，its surface was reddish brown to dark red ，with slight shrinkage. Its taste was sweet ，sour and slightly astringent. The microscopic characteristics of the powder were clear ，the stone cells were scattered individually or clustered，and the pulp parenchyma cells contained calcium oxalate cube crystal and cluster crystal. The results of TLC showed that there were fluorescent spots of the same color in the chromatogram of the tested product and the corresponding position of the reference substance （ursolic acid ）. The content ranges of moisture ，total ash and extracts were 9.02％-11.39％，2.29％-3.35％， 37.12％-58.41％ respectively. The linear ranges of chlorogenic acid ，hyperin，isoquercitrin，，quercetin phlorizin and quercetin were 3.12-50，1.25-20，1.25-20，3.12-50，18.7-300，0.5-8 μg/mL（all r were not less than 0.999 7）. RSDs of prescision ，stability and reproducibility tests were all lower than 3.0％（n＝6）. The average recoveries were 97.56％，98.28％，106.14％，103.74％， 98.37％，98.76％；RSDs were 1.57％，1.62％，1.38％，1.99％，2.15％，2.31％（n＝6）. The content ranges of the above six components in 20 baches of samples were 0.001 5％-0.028 8％，0.005 9％-0.022 0％，0.008 7％-0.030 4％，0.019 4％- 0.048 5％，0.068 5％-0.199 8％ and 0.005 1％-0.081 4％. CONCLUSIONS ：Established method is accurate and stable ，and can be used for quality control of Malus Fructus. It is preliminarily Δ 基金项目：四川省科技计划项目（No.2020YFS0495）；“杏林学 proposed that moisture and total ash content should not exceed 者”学科人才科研提升计划（No.CXTD2018016） 12％ and 3.5％，and extract （by dry product ）and phlorizin ＊硕士研究生 。研究方向 ：中药品种 、质量与资源 。E-mail： content should not be less than 40％ and 0.1％ respectively. 1159020313@qq.com # 通信作者：教授。研究方向：中药品种、质量与资源。E-mail：  
          
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        发布时间：2022-06-21
      • LI Xue ’e,ZHANG Shu,DENG Hong,LYU Zhufen,TAN Yulin,CHEN Jiamin,YU Yushan
        Vol. 31, Issue 21, (2020)
        摘要：OBJECTIVE：To optimize the formul ation of Polygala japonica cream，and to evaluate the quality of prepared cream. METHODS ：With centrifugal stability ，heat resistance stability and viscosity as evaluation indexes ，the weight coefficient was determined by analytic hierarchy process （AHP），criteria importance through intercriteria correlation （CRITIC）method and mixed weighted AHP-CRITIC ，and the comprehensive score was calculated. The amount of octadecyl alcohol ，hexadecanol and mixed emulsifier （polysorbate 60 mixed with glycerin monostearate at the mass ratio of 2.82）in the formulation of P. japonica cream were screened by central composite design-response surface methodology. The optimized formulation was validated. P. japonica cream prepared by the optimal preparation was evaluated in terms of apperance ，particle，pH，stability and rheological characteristics. RESULTS ：The weight coefficients of centrifugal stability ，heat resistance stability and viscosity were 0.428 5， 0.415 6 and 0.155 9 respectively，according to the mixed weighted AHP-CRITIC. The optimal formulations were 1.96 g of hexadecyl alcohol ，5.17 g of octadecyl alcohol ，2.48 g of mixed emulsifier ，1.83 g of polysorbate 60，0.65 g of glyceride monostearate，1 g of benzyl alcohol ，5 g of propylene glycol ，6 g of isopropyl myristate and 5 g of P. japonica extract，and then added water to 100 g. Prepared cream was a light yellow fluid paste with particle size of 0.5-2.5 μm and pH value of 6.5；the results of centrifugal test ，heat resistance test and cold resistance stability test showed that the cream had no oil-water separation or thickened paste. The prepared cream was shear-thinning non-Newtonian fluid. CONCLUSIONS ：P. japonica cream is prepared successfully，which shows good apperance ，particle，acidity and stability.  
          
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        发布时间：2022-06-21
      • DONG Xiaoliu,SONG Lihua,DONG Wei,GAO Ming,ZHANG Xiuqing,LIU Weiran,XU Shijun,LIU Tiejun,CUI Lusha
        Vol. 31, Issue 21, (2020)
        摘要：OBJECTIVE：To in vestigate the effects of dexmedetomidine （Dex）on SIRT 1/Akt/GSK3β/β-catenin signaling pathway in cerebral injury of sepsis model rats ，and explore the mechanism of its protecitve effect on cerebral injury. METHODS ： A total of 80 male SD rats were randomly divided into sham operation group （Sham group ），sepsis group （CLP group ），CLP+Dex group（10 μg/kg Dex），CLP+Dex+Sirtinol group （10 μg/kg Dex+2 μL/100 g SIRT 1 inhibitor sirtinol ），with 20 mice in each group. Two hours before modeling ，CLP+Dex+Sirtinol group was injected with sirtinol via lateral ventricle. Sepsis model was induced by cecal ligation and perforation in each group （in sham group ，only operation was performed but no ligation was performed）. At 0，3，6 h after modeling ，CLP+Dex group and CLP+Dex+Sirtinol group were given Dex （10 μg/kg） intraperitoneally，Sham group and CLP group were given constant volume of normal saline intraperitoneally. Cerebral tissue water content，Evans blue （EB）content，apoptosis in cerebral cortex ，the levels of IL- 1β and TNF-α in cerebral tissue as well as the protein expression of SIRT 1，p-Akt，p-GSK3β and β-catenin in hippocampus were detected 24 h after last medication. RESULTS ： Compared with Sham group ，cerebral tissue water content ，EB content ，the number of apoptotic cells in cerebral cortex as well as the levels of IL- 1β and TNF-α in cerebral tissue were increased significantly（P＜0.05），while the protein expression of SIRT 1， p-Akt，p-GSK3β and β-catenin in hippocampus were decreased significantly （P＜0.05）. Compared with CLP group ，cerebral tissue water content ，EB content ，the number of apoptotic cells in cerebral cortex as well as the levels of IL- 1β and TNF-α in cerebral tissue were decreased significantly in CLP+Dex group （P＜0.05），while the protein expression of SIRT 1，p-Akt，p-GSK3β and β-catenin in hippocampus were increased significantly （P＜0.05）. Sirtinol could significantly reverse the above-mentioned cerebral protection and factor regulation effects of Dex （P＜0.05）. CONCLUSIONS ：Dex can protect the cerebral tissue of sepsis model rats，which may play an anti-inflammatory and anti-apoptotic role by activating SIRT 1/Akt/GSK3β/β-catenin signaling pathway ，so as to reduce cerebral edema ，protect blood-brain barrier and reduce cerebral injury.  
          
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        发布时间：2022-06-21
      • LIU Teng,XU Jinfang,LU Xiaolin,HOU Hongbao,LI Zhenyu,QU Tingli,ZHAO Zhengbao
        Vol. 31, Issue 21, (2020)
        摘要：OBJECTIVE：To study the intervention effects of Huan gqi injecti on on leucopenia model mice. METHODS ： Kunming mice were randomly divided into normal group ，model group and drug group ，with 8 mice in each group. Model group and drug group were given intraperitoneal injection of cyclophosphamide to induce leukopenia model. Normal group was given intraperitoneal injection of equal volume of sterile water. After modeling successfully ，normal group and model group were given intraperitoneal injection of equal volume of sterile water ；drug group was given intraperitoneal injection of Huangqi injection 0.04 mL/10 g，once a day ，for consecutive 7 d. Based on the detection of blood routine indexes （leukocyte，lymphocyte，neutrophil， monocyte count ）of mice in each group ，the metabolites in serum were analyzed by LC-MS. Principal component analysis （PCA）， partial least squares discriminant analysis （PLS-DA），orthogonal partial least squares-discriminant analysis （OPLS-DA），HMDB， METLIN， KEGG and other databases as well as related literatures were used to identify the differential metabolites. The metabolic pathways of differential metabolites were analyzed with MetPA online tools ，and the correlation of blood routine indexes and differential metabolites were analyzed on the basis of Pearson correlation coefficient. RESULTS： Compared with normal group ， blood rountine indexes of model group were decreased significantly （P＜ 0.01）. Compared with model group ，above blood r ountine indexes of drug group were all increased siginificantly （P＜0.01）. LC-MS chromatogram of serum samples in normal group and model group were significantly different ，and LC-MS metabonomics data of serum samples in drug group were similar to those of normal group. Multivariate statistical analysis and correlated database analysis revealed that compared with normal group ，serum contents of 17 metabolites as L-isoleucine，eicosapentaenoic acid were increased significantly in model group ，while the contents of 4 metabolites as spermidine were decreased significantly （P＜0.05 or P＜0.01）. Compared with model group ，Huangqi injection could reverse the serum contents of 9 metabolites in mice ，such as citric acid ，L-proline，acetylcarnitine，L-isoleucine， L-phenylalanine，sphingosine-1-phosphate，lysophosphatidylinositol，eicosapentaenoic acid and linoleic acid （P＜0.05 or P＜ 0.01），which were associated with linoleic acid metabolism ，biosynthesis of phenylalanine ，tyrosine and tryptophan ，and phenylalanine metabolism （metabolism pathway influential values were all higher than 0.1）. Correlation analysis showed that there was a significant correlation between blood routine indexes and the contents of D-sphingosine，linoleic acid and citric acid in model group（the absolute values of r were generally greater than 0.5）. CONCLUSIONS ：Huangqi injection can increase the counts of leukocytes，lymphocytes，neutrophils and monocytes in leucopenia model mice. The increase of leukocytes may be related to linoleic acid metabolism ，biosynthesis of phenylalanine ，tyrosine and tryptophan ，and phenylalanine metabolism.  
        关键词：Huangqi injection;Leucopenia;Cyclophosphamide;LC-MS;Metabolomics;Mice   
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      • MA Bin,CHAI Zhi,WANG Jinhong
        Vol. 31, Issue 21, (2020)
        摘要：OBJECTIVE：To provide referenc e for intuitively and c onveniently cognizing the research focus of Astragalus membranaceus in the treatment of diabetes. METHODS ：Using the method of bibliometrics ，the literatures about the treatment of diabetes by A. membranaceus were retrieved from CNKI full-text database during Jan. 1st，2000-Jun. 30th，2020. Bibliometric method was used to statistically analyze the number of articles ，authors and their research directions ，keywords，distribution of research institutions ，source journals ，frequency of citations ，fund funding ，etc. VOSviewer software was used for visual display. RESULTS：A total of 2 960 literatures were included ，and the number of literatures showed an increasing trend ；the author with the most literatures was Fan Ying from Liaoning University of TCM ，whose research direction was the effect of different effective parts of A. membranaceus on serum insulin and adiponectin in diabetic animal models ；in the keyword frequency analysis ，diabetic nephropathy（845 times），A. membranaceus （615 times），diabetes（587 times），A. membranaceus injection（350 times），diabetic peripheral neuropathy （303 times），qi tonifying drug （202 times）were hot topics. There were 10 institutions with more than 20 literatures，of which Nanjing University of TCM has published the most literatures （58 pieces）. Shaanxi Journal of Traditional Chinese Medicine ，Chinese Journal of Integrated Traditional and Western Nephropathy and Inner Mongolia Journal of Traditional Chinese Medicine were the journals with a large number of； literatures；Research Progress on Chemical Constituents and Pharmacological Effects of Astragalus membranaceus published from Chen guohui and others was cited most frequently，for 690 times；there are many projects funded by national scientific research funds （including National Natural Science Foundation of China and the National Key Basic m Research Special Foundation of China ）. CONCLUSIONS ：In the past 20 years， the level of researches about A. membranaceus in the treatment of diabetes have been steadilyimproved. However ，the distribution of literature is uneven and there are few high-quality core journals. Mainly ，there are relatively few clinical trials. It is suggested that researchers should explore the methods and ideas of A. membranaceus in the treatment of diabetes from the perspectives of macro clinical efficacy ，micro pharmacology ，A. membranaceus genetic resource bank and traditional Chinese medicine formulations.  
          
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      • CHEN Gong,YANG Fang,WEI Gang,LI Xiaoping,LI Ming,ZHANG Yaling
        Vol. 31, Issue 21, (2020)
        摘要：OBJECTIVE：To observe the clinical effect and safety of recombinant human brain natriuretic peptide （rhBNP） combined with levosimendan in the treatment of acute decompensated heart failure （ADHF）complicated with renal insufficiency. METHODS：A total of 156 patients with ADHF complicated with renal insufficiency admitted to the Dept. of Cardiology in the Affiliated Hospital of Southwest Medical University during Jan.-Dec. 2019 were randomly divided into rhBNP group ，levosimendan group and combination group ，with 52 patients in each group. All patients received rountine treatment. On this basis ，rhBNP group was given rhBNP for injection [after 1.5 μg/kg intravenous pulse injection，intravenous dripping for 24 h with 0.007 5 μg（/ kg· min）]；leosimendan group was given Leosimendan injection 12.5 mg [intravenous dripping for 1 h with 6-12 μg（/ kg·min），then intravenous dripping for 23 h with 0.1 μg（/ kg·min）]. Combination group received drug combination according to the administration method of single drug group. Three groups received treatment for consecutive 7 d. Cardiac function indexes [heart rate （HR），left ventricular ejection fraction （LVEF），left ventricular end-diastolic diameter （LVEDD）]，mean arterial pressure （MAP），pulmonary capillary pressure （PCWP），renal function indexes [estimated glomerular filtration rate （eGFR），serum creatinine （Scr）]，serum levels of cystatin C （Cys-c）and amino-terminal brain natriuretic peptide precursor （NT-proBNP）were observed in 3 groups before and after treatment. Clinical efficacy and the occurrence of ADR were recorded. RESULTS ：Three cases withdrew from the study in rhBNP group and 1 case in levosimendan group ；152 cases completed the study. Before treatment ，there was no statistical significance in cardiac function indexes ，MAP，PCMP，renal function indexes or serum levels of Cys-C and NT-proBNP among 3 groups（P＞0.05）. After treatment ，the HP ，MAP，PCWP and serum level of NT-proBNP in 3 group as well as serum level of Cys-C in combination group were decreased significantly （P＜0.05）；the LVEF in 3 group as well as the eGFR and Scr level in levosimendan group and combination group were significantly increased （P＜0.05），compared with before treatment ；above indexes of combination group were significantly better than those of rhBNP group and levosimendan group （P＜0.05）. Total effective rate of combination group was 94.23％ ，which was significantly higher than those of rhBNP group （77.55％）and levosimendan group （76.47％）（P＜0.05）. There was no significant difference in the incidence of ADR among 3 groups（P＞ 0.05）. CONCLUSIONS ：rhBNP combined with levosimendan in the treatment of ADHF complicated with renal insufficiency can significantly increase the clinical efficacy ，and improve cardiac and renal function but don ’t increase the incidence of ADR.  
          
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      • ZHOU Xuelai,YANG Yuan,DAI Wei,XUAN Zhihong,WANG Yifei
        Vol. 31, Issue 21, (2020)
        摘要：OBJECTIVE：To investigate t he effects of Baihe gujin decoction combined with Shenmai injection on therapeutic efficacy and related indexes in elderly patients with ventilator-associated pneumonia. METHODS ：A total of 75 elderly patients with ventilator-associated pneumonia who were admitted to the Intensive Care Unit （ICU）of Zhuji Hospital of TCM from Apr. 2018 to Oct. 2019 were included. They were randomly divided into control group ，Shenmai group ，Baihe gujin decoction+Shenmai group ， with 25 cases in each group. Control group was given conventional treatments as Piperacillin sodium tazobactam sodium injection 4.5 g，ivgtt，q8 h for anti-infective treatment+ Ambroxol hydrochloride injection 4 mL，iv，bid for expectorant+ Doxofylline injection 20 mL，qd for relieving spasm and asthma+maintaining water ，electrolyte and acid-base balance. Shenmai group was given Shenmai injection 100 mL，ivgtt，qd，on the basis of control group. Baihe gujin decoction+Shenmai group was given Baihe A101） gujin decoction 200 mL nasally ， morning and evening ，on m the basis of Shenmai group. Each group took 7 days as a course of treatment ，and the treatment was continued for 2 courses. Acute physiology and chronic health status （APACHE）Ⅱ score，C-reactive protein （CRP）in peripheral blood ，procalcitonin（PCT），bronchial CD 68 count were observed in 3 groups before and after treatment while the mechanical ventilation time ，hospitalization time in the ICU and ADR recorded. RESULTS：Before treatment ，there was no statistically significant difference in APACHE Ⅱ score，the levels of CRP and PCT ， bronchial CD 68 count among 3 groups（P＞0.05）. After 14 days of treatment ，APACHE Ⅱ score，CRP and PCT levels of all 3 groups were significantly lower than before treatment ；bronchial CD 68 count was significantly higher before treatment ，the order of bronchial CD 68 cell count was Baihe gujin decoction+Shenmai group ＞Shenmai group ＞control group （P＜0.05 or P＜0.01）；after 7 days of treatment ，the order of CRP and PCT levels was Baihe gujin decoction+Shenmai group ＜Shenmai group ＜control group （P＜0.05）；after 14 days of treatment ，there was no staistically significant difference in APACHE Ⅱ score，CRP and PCT levels among 3 groups（P＞0.05）. After treatment ，the order of mechanical ventilation time and ICU hospitalization time was Baihe gujin decoction + Shenmai group ＜Shenmai group ＜control group （P＜0.05 or P＜0.01）. There was no significant difference in the incidence of ADR among 3 groups（P＞0.05）. CONCLUSIONS ：Based on routine treatment ，Baihe gujin decoction combined with Shenmai injection can improve the immune function of lung macrophages in the elderly patients with ventilator-associated pneumonia，inhibite pulmonary inflammation progress ，reduce mechanical ventilation time ，shorten the length of hospital stay with good safety.  
          
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      • TANG Lian,SHI Lu,XUE Hongzhi,ZHUANG Zhiwei,YUAN Yunlong,QIAN Chunxia,ZHU Jinwei,XU Xiaowen,ZHU Yasong,LIU Jisong,SHEN Yi,LU Jian
        Vol. 31, Issue 21, (2020)
        摘要：OBJECTIVE：To study the effects of augmented renal clearance （ARC）on blood trough concentration of patients receiving high-dose regimen of teicoplanin. METHODS ：Patients who received high-dose regimen of teicoplanin in the ICU were prospectively collected from the Affiliated Suzhou Hospital of Nanjing Medical University/Suzhou Municipal Hospital during Jul. 2018-Jun. 2020. They were divided into ARC group and normal renal function group according to corrected creatinine clearance. The dosage regimen of teicoplanin in the two groups were loading dose of 600 mg，q12 h×3 doses，maintenance dose of 6-10 mg/kg，qd，and the dosage was adjusted in combination with creatinine clearance rate and blood trough concentration. The trough concentration of blood samples which were collected 30 min before the 4th and 8th-10th dosage of teicoplanin were determined by HPLC. Trough concentration ，clinical efficacy ，Gram-positive bacterial clearance rate and the occurrence of ADR were compared between 2 groups. RESULTS ：A total of 56 patients were included and divided into ARC group （18 cases）and normal renal function group （38 cases）. ARC group had younger age （P＜0.001）and lower serum albumin level （P＝0.025）than normal renal function group. The trough concentrations before administration of the 4th and 8th-10th dosage in ARC group were lower than normal renal function group （P＝0.034；P＝0.035）. The trough concentrations in the ARC group and normal renal function group before 8th-10th dosage were all higher than 30 min before the 4th dosage （P＝0.003；P＜0.001）. The clinical efficacy rate and the clearance rate of Gram-positive bacteria in ARC group were 77.8％ and 76.2％，which were lower than those of the normal renal function group ，but there was no statistical difference （P＝0.195；P＝0.223）. There was no liver function damage ，hemocytopenia and allergic reaction in both groups ，but in the normal renal function group ，the causal relationship between acute renal damage and teicoplanin was assessed as “very likely ”in one patient. CONCLUSIONS ：ARC patients are younger ，most of them have hypoproteinemia，and the blood trough concentrations of teicoplanin in high-dose regimen are significantly lower than those of normal renal function patients. For critical ill ARC patients ，it is advisable to increase the loading dose of teicoplanin to make the trough concentration reach the target concentration range quickly.  
        关键词：Augmented renal clearance;Teicoplanin;High dosage;Blood trough concentration;Clinical efficacy   
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      • LIAN Guan,XIE Zhuolin,LI Meixuan,LI Yongkun,ZHANG Dinghua
        Vol. 31, Issue 21, (2020)
        摘要：OBJECTIVE：To reappraise systematic review/Meta-analysis （SRs/MAs）of the efficacy and safety of glucagon-like peptide 1（GLP-1）receptor agonist in the treatment of type 2 diabetes mellitus （T2DM），and to provide evidence-based reference for clinical use of these drugs in the treatment of T 2DM. METHODS ：Retireved from Cochrane library ，PubMed，Embase，CBM， Wanfang database and CNKI ，systematic review/Me ta-analysis about GLP- 1 receptor agonist in the treatment of T 2DM were collected during the inception to Dec. 2019. After data extraction of literatures met inclusion and exclusion criteria ，GRADE system was used to evaluate the quality of evidence included in the study ，and the evidence of efficacy and safety outcome indexes were summarized. RESULTS ：Finally 31 literatures were included ，involving 91 outcome indexes ，and GRADE evidence quality was medium，among which 4（4.4％）were very-low-quality ，33（36.3％）were low-quality ，45（49.5％）were medium-quality ，and 9 （9.9％）were high-quality outcome indicators. The results of evidence summary showed that GLP- 1 receptor agonists were better than or similar to placebo and other oral hypoglycemic drugs ， better than dipeptidyl peptidase 4 （DPP-4） inhibitors in . reducing the level of HbA 1c；better than or similar to placebo ， JDZX2015240） better than other oral hypoglycemic agents and DPP- 4 2276299207@qq.com inhibitors in reducing the level of fasting glucose ；similar to DDP-4 inhibitors，higher than or similar to placebo ，lower than other oral hypoglycemic dru gs in the incidence of hypoglycemia；higher than other oral hypoglycemic drugs ，placebo and DPP- 4 inhibitors in the incidence of diarrhea and nausea ； higher than other oral hypoglycemic drugs and placebo in the incidence of vomiting. CONCLUSIONS ：The evidence quality of systematic review/Meta-analysis about GLP- 1 receptor agonist in the treatment of T 2DM are moderate. These drugs have good clinical efficacy in the treatment of T 2DM，but their safety are not as good as placebo or other oral hypoglycemic drugs.  
        关键词：Glucagon like peptide 1 receptor agonist;Type 2 diabetes mellitus;Reappraisal of systematic review;GRADE   
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      • QU Jiling,SHEN Yijing,ZHOU Ting,LIU Yongbing
        Vol. 31, Issue 21, (2020)
        摘要：OBJECTIVE：To analyze the research status and hotspot frontier of polypharmacy in the elderly in recent ten years ， and to provide reference for polypharmacy study in the elderly in China. METHODS ：The related literatures about polypharmacy in the elderly were retireved from Web of Science core database during Jan. 1st，2010-Dec. 31th，2019. CiteSpace 5.6.R5 software was used to analyze the quantity of pulished literatures ，authors，country/area，institution，co-citation of journals and literatures. The keywords were taken as nodes for co-occurrence analysis ，cluster analysis and Burst analysis ，the visual maps were drawn and the results were analyzed. RESULTS ：A total of 3 521 literatures were included ，and the quantity of published literatures about polypharmacy in the elderly was on the rise ；high-yield authors mainly were Bell JS and Hilmer SN which were the representative with 36 papers published ，accounting for 1.02％ of the total. America （929 literaturesm 26.3％）and University of Sydney （101 literatures，2.87％）were the most high-yield country and institution respectively ；Journal of the American Geriatrics Society was the journal with the most articles （2 202 pieces）. The most frequently cited literature was those published by Radcliff S team in 2015 to update Beers standard to reduce potential inappropriate drug use ；the research on how to optimize the prescription for the elderly published by Spinewine A team in 2007 had the highest co-citation centrality. The hot keywords were elderly ，polypharmacy and risk factor ；keywords with high centrality included quality of life ，polypharmacy and Beers standard. Research hotspots included risk factor ，outcome index and reduction strategy for polypharmacy. Six clusters were formed ，including Breast cancer ， Prescription，Disorder，Schizophrenia，Mediation attachment and Trial ；complications，pain，frailty，health-related quality ， intellectual disability were at the forefront of research. CONCLUSIONS ：In the past 10 years，the research on polypharmacy in the elderly has been paid more and more attention by scholars ；the United States and Australia have made great contributions in this field；the research mainly focused on the impact of polypharmacy on health outcomes and the strategies for reduce polypharmacy. In the future ，more attention will be paid to the related research on psychological ，cognitive and debilitating effects of polypharmacy in the elderly.  
        关键词：Elderly;Polypharmacy;Bibliometrics;Web of Science   
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      • SU Changhai,LIU Junbao,XIE Peitao,HAO Duo,ZHANG Xiaojuan
        Vol. 31, Issue 21, (2020)
        摘要：OBJECTIVE：To provide th e ideas a nd for individualized anti-infective treatment of infection after surgery for infants and young children with intussusception and enterobrosis ，and to provide reference for clinical pharmacists participating in the clinical treatment. METHODS ：Clinical pharmacists optimized the anti-infection program for an 11-month-old infant patient infected after surgery with intussusception and enterobrosis in Ordos Central Hospital ；they put forward medication suggestions in respects of the selection of initial anti-infection treatment program ，drug replacement ，the selection of anti-infection treatment program after blood culture showed Enterococcus coli and Enterococcus faecium ，and dosage adjustment. RESULTS ：According to the judgment of the common pathogens and the hospital or community infections in the infant patient with intussusception and enterobrosis，cefoperazone sulbactam 1.0 g，q12 h was adjusted to cefoperazone sulbactam 0.5 g，q8 h combined with Metronidazole chloride sodium injection 20 mL，q8 h；when the blood culture showed E. coli （ESBL-）and E. faecium ，it was recommended to add vancomycin 0.15 g，q12 h. After poor treatment ，it was recommended to adjust the vancomycin dose to 0.2 g，q8 h. All the above suggestions were adopted by doctors. And the child ’s body temperature dropped after treatment ，the blood culture turned negative and laboratory indicators returned to normal. The child was discharged smoothly. CONCLUSIONS ：Infants and young children are special groups. Therefore ，before using antibiotics ，clinical pharmacists should evaluate the age ，body weight ，liver and kidney functions of infants and young children. They should also help doctors select and adjust drugs ，frequency and dosage on the basis of pharmacokinetic characteristics and safety ，so as to avoid adverse drug reactions while ensure curative effect.  
        关键词：Infant;Intussusception;Enterobrosis;Abdominal infection;Anti-infection;Clinical pharmacists   
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