最新刊期

    32 11 2021
    • XIAO Yong,SHEN Shaowu,CHANG Kai,GU Gaosheng
      Vol. 32, Issue 11, (2021)
      摘要:OBJECTIVE:To provi de reference for the construction of shared TCM pharmacy information platform based on county medical alliance. METHODS :By literature research ,the construction and development of TCM pharmacy in primary medical and health institutions were analyzed ,and the feasibility ,advantages and limitations of shared TCM pharmacy based on county medical alliance were also analyzed. The construction process and method of shared TCM pharmacy information platform based on county medical alliance introduced from aspects of overall architecture ,business model and main functions. RESULTS & CONCLUSIONS:The policies for the revitalization and development of medical alliance and TCM ,the needs for the improvement of grass-roots TCM service ability ,and the application of modern information technology provide the feasibility for the construction of shared TCM pharmacy based on county medical alliance. The construction of shared TCM pharmacy based on county medical alliance can broaden TCM list in the primary medical institutions ,integrates and diverts human resources ,save costs ,and provides homogeneous and standardized pharmaceutical care. However ,it is generally affected by non information technology factors such as county regional environment ,policy support ,logistics distribution speed ,cost benefit sharing. T he shared TCM pharmacy information platform based on county medical alliance is mainly based on the TCM alliance led by county-level TCM hospital ,and constructs business model from three aspects :business processing ,business management and business sharing on the basis of the health information platform of TCM department. Its main functions include the whole flow management of TCM decoction pieces , TCM dispensing ,decocting,distribution,pharmaceutical care ,quality control ,convenient service and interface management and so on. The application of shared TCM pharmacy information platform based on county medical alliance helps the opening of the business cooperation and information sharing channel of shared TCM pharmacy based on county medical alliance expands the service scope of TCM ,and enhances the TCM service ability in primary medical institutions.  
      关键词:County;Medical alliance;Shared TCM pharmacy;Information platform   
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      发布时间:2022-06-21
    • LI Yuan,MENG Guangxing
      Vol. 32, Issue 11, (2021)
      摘要:OBJECTIVE:To stu dy the effects of R&D expense additional deduction policy on R&D investment and profitability of pharmaceutical manufacturing industry , and to provide reference for improving R&D investment and profitability of pharmaceutical manufacturing industry. METHODS :Based on the data of Chinese pharmaceutical listed enterprises during 2012-2019,regression discontinuity design and descriptive method were adopted to analyze the effect of R&D expenses additional deduction policy on R&D investment and profitability of pharmaceutical manufacturing industry. RESULTS :Both R&D investment and the main business profit margin had significant “jump”at the policy cutoff point ,and the policy effect coefficient of the R&D expenses additional deduction policy on R&D investment and profitability of the pharmaceutical manufacturing industry were 0.310 and -1.197 respectively(P<0.001). The policy effect coefficient of the policy on R&D investment in the eastern region was 0.413(P<0.001),while the effect on central and western regions were not significant ;the policy effect coefficient of the policy on R&D investment of large-scale and small- and medium-scale pharmaceutical manufacturing industry were 0.502 and 0.264 respectively(P<0.001). CONCLUSIONS :On the whole ,R&D expenses additional deduction policy has a positive incentive impact on R&D investment of pharmaceutical manufacturing industry ,but does not have a positive incentive impact on the profitability which is greatly affected by other factors. The policy has regional differences in the incentive impact on R&D investment of pharmaceutical manufacturing industry ;the incentive impact of the policy on the R&D investment of large-scale pharmaceutical manufacturing industry is better than that of small-and medium-scale one. It is recommended to improve the R&D expenses additional deduction policy ,reasonably increase the profit margin of the pharmaceutical manufacturing industry ,adjust the policy for different regions and focus on guiding policies to favor small- and medium-scale pharmaceutical manufacturing industry,so as to improve the R&D investment and profitability of pharmaceutical manufacturing industry.  
        
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      发布时间:2022-06-21
    • ZHAO Mengxia,SHEN Jie,MAO Zhihai,HE Shengliang
      Vol. 32, Issue 11, (2021)
      摘要:OBJECTIVE:To unscramble the Notice on Standardizing the Allocation and Use of Licensed Pharmacists in Drug Retail Enterprises (called Notice for short )and related document ,and to give some suggestions to provide reference for the industry and policy decision departments. METHODS :The background and content of Notice were described briefly ;the problemsexisting in the corresponding provincial differentiated allocation policy and the difficulties existing in the implementation were analyzed to give some relevant suggestions. RESULTS & CONCLUSIONS :The main contents of Notice contained adhering to the policy of licensed pharmacists ,steadily improving the allocation level of licensed pharmacists ,refining and implementing the allocation requirements ,and strengthening the implementation of supervision and inspection responsibilities ;giving full play to the role of licensed pharmacists and continuously strengthening the team building. At present ,drug administrations of many provinces in China have issued specific policies on the differentiated allocation of licensed pharmacists and pharmaceutical technicians ,which are mainly divided into four schemes. The author believes that the classification method of drug retail enterprises implemented in Shandong and Guangdong provinces are the most scientific. The implementation of differentiated allocation of pharmacists with health(pharmacy)professional title in drug retail enterprises can alleviate the problem of insufficient licensed pharmacists to a certain extent ,but the disadvantage is that it can not achieve accurate registration and control as well as the management of licensed pharmacists ,which is easy to produce policy gaps ;after the “affiliation licensed pharmacist ’s certificate ”phenomenon, the“certificate affiliation of pharmacist with health (pharmacy)professional title ”phenomenon appeared. It is suggested that the provincial drug supervision and administration departments should try the differentiated allocation scheme of hierarchical management;learn from the management experience of licensed pharmacists and pharmaceutical technicians in Guangdong province, develop relevant platforms to manage the information of pharmaceutical technicians uniformly ; strengthen the communication and interaction with the health and human resource security department as well as the mutual promotion mechanism of personnel information screening ,so as to solve the core bottleneck of licensed pharmacists ’quality.  
        
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      发布时间:2022-06-21
    • XU Wanpeng,LIN Jun,LIANG Yingqin,ZHOU Huanfang,ZHANG Hua,HUANG Shizhen,SUN Xuemei,WEI Xiugui,WANG Hongyuan,LIU Lin
      Vol. 32, Issue 11, (2021)
      摘要:OBJECTIVE:To inv estigate the effects of 4-hydroxy-2(3H)-benzoxazolone on inflammatory and apoptosis signaling pathways in non-alcoholic fatty liver disease (NAFLD)model rats. METHODS :SD rats were divided into normal control group(10 rats)and modeling group (50 rats). Normal control group was given basic diet ,and modeling group were given high-fat diet to induce NAFLD model. After modeling ,the rats were divided into normal control group ,model group ,silibinin group (26.25 mg/kg),and 4-hydroxy-2(3H)-benzoxazolone high-dose ,medium-dose and low-dose groups (100,50,25 mg/kg),with 8 rats in each group. Normal control group and modeling group were given 0.6% CMC-Na intragastrically ,and other groups were given relevant medicine 10 mL/kg intragastrically ,once a day ,for consecutive 4 weeks. After last medication ,the serum levels of albumin(ALB),total protein (TP),globulin(GLB),ALB/GLB and free fatty acid (FFA)were detected ;TUNEL staining was used to observe the apoptosis of rat hepatocytes. Western blot assay was used to detect the protein expression and phosphorylation level of inflammatory signaling pathway related proteins [Toll-like receptor 4(TLR4),myeloid differentiation factor 88(MyD88), nuclear factor-κB p65(NF-κB p65),NF-κB inhibitor protein(IκBα)] in liver tissue as well as the expression of apoptosis signaling pathway related proteins [B cell lymphoma 2(Bcl-2),Bax,caspase-3]. RESULTS :Compared with model group ,serum levels of TP (except for low-dose group ),GLB and FFA ,the protein expression of TLR 4(except for low-dose group ),MyD88 (except for medium-dose group )and caspase- 3,the phosphorylation levels of NF-κB p65 and IκBα protein were decreased significantly(P<0.05 or P<0.01). The ratio of A LB/GLB in serum and the ratio of Bcl- 2/Bax in liver tissue were significantly increased(P<0.05 or P<0.01),and the phenomenon of hepatocyte apoptosis was improved. CONCLUSIONS :4-hydroxy-2 (3H)-benzoxazolone can ameliorate NAFLD in rats ,and the mechanism may be associated with inhibiting the expression TLR 4/ MyD88/NF-κB signaling pathway-related proteins and apoptosis-related proteins in liver tissues.  
        
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      发布时间:2022-06-21
    • LI Yueting,LIU Ting,WU Qiong,LU Dingyan,WANG Mingjin,WANG Yonglin,LI Yongjun,ZHOU Meng,LIU Chunhua
      Vol. 32, Issue 11, (2021)
      摘要:OBJECTIVE:To study the improvement effects and mechanism of Polygonum orientale flower extract on hypoxia- reoxygenation injury of H 9c2 cardiomyocytes. METHODS :H9c2 cardiomyocytes were divided into normal control group ,model group and low- ,medium- and high-concentrations groups of P. orientale flower extract (20,40,80 μg/mL). Except for normal control group ,other groups were given 800 μmol/L CoCl2 to induce hypoxia-reoxygenation injury model. Cell apoptosis was observed. The levels of Ca 2+(in cytoplasm ),mitochondrial membrane potential (MMP),ATP enzyme (Na+-K+-ATP enzyme ,Ca2+-Mg2+-ATP enzyme) activities, the ratio of cytochrome c (Cyto c ), protein in cytosol to mitochondria ,phosphorylation levels of reperfusion injury salvage kinase (RISK) signaling pathwayrelated protein [protein kinase B (Akt)and extracellular signal regulated kinase 1/2(ERK1/2)] as well as protein expression of HIF- 1 α were detected respectively. In addition,the cells were divided into normal control group ,model group and P. orientale flower extract group (80 μ g/mL),PI3K inhibitor LY294002+CoCl2 group(15 μmol/L LY294002+80 μmol/L ,LY294002+P. orientale flower extract group (15 μmol/L LY294002+80 μg/mL P. orientale flower extract ),MEK inhibitor PD98059+CoCl2 group(25 μmol/L PD98059+800 μmol/L CoCl2),PD98059+P. orientale flower extract group (25 μmol/L PD98059+80 μg/mL P. orientale flower extract ). After cultured by the same method ,the phosphorylation levels of Akt protein and ERK1/2 protein in the cells were measured to verify the activation of P. orientale flower extract to RISK signaling pathway. RESULTS:Compared with model group ,nuclear pyknosis and the number of apoptotic bodies were reduced in different concentrations groups of P. orientale flower extract. ROS level ,Ca2+ level(except for low-concentration group ),MMP,ratio of Cyto c in cytoplasm to Cyto c in mitochondria ,protein expression of HIF- 1α were decreased significantly(P<0.05 or P<0.01); the activity of ATP enzyme (except for the low-concentration group ),Akt protein and ERK 1/2 protein phosphorylation level were significantly increased (P<0.01). After treated with PI 3K inhibitor LY 294002 and MEK inhibitor PD 98059,Akt protein and ERK 1/2 protein phosphorylation level in cadiomyocyte were decreased significantly (P<0.05 or P<0.01). CONCLUSIONS :P. orientale flower extract can improve hypoxia-reoxygenation injury of H 9c2 cardiomyocytes,the mechanism of which may be associated with inhibiting cardiomyocyte apoptosis ,improving ATPase activity ,protecting mitochondria ,regulating RISK signaling pathway related proteins and HIF- 1α protein expression.  
        
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      发布时间:2022-06-21
    • FENG Jingqian,LI Jiangyan,SONG Jianfeng,WANG Siwei,MAO Bizeng
      Vol. 32, Issue 11, (2021)
        
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    • WANG Mingming,WANG Lei,DOU Fang,LI Weiwei,WEN Aidong,WANG Jingwen
      Vol. 32, Issue 11, (2021)
      摘要:OBJECTIVE:To study the imp rovement effects of β-boswellic acid on hippocampal neurons cells injury of rats induced by oxygen-glucose deprivation. METHODS :The hippocampal neurons cell of rats were divided into normal control group , model group and β-boswellic acid low-concentration ,medium-concentration and high-concentration groups (1,10,100 μmol/L). Except for normal control group ,other groups were cultured with relevant medium and given oxygen glucose deprivation to induce oxygen-glucose deprivation induced injury model. MTT assay was adopted to detect cell viability. Chemical colorimetry was used to detect LDH activity in cell culture supernatant. Hoechst-PI staining was used to detect the morphology change of cells. Flow cytometry was used to detect early apoptosis rate of cells. The expression of apoptosis-related protein (Bcl-2,Bax and cleaved caspase-3) were detected by Western blot. RESULTS :Compared with model group ,the survival rate of cells and protein expression of Bcl- 2 were increased significantly in β-boswellic acid medium-concentration and high-concentration groups (P< 0.01),while LDH activity ,early apoptosis rate ,protein expression of cleaved caspase- 3 and Bax were all decreased significantly (P<0.05 or P<0.01). The densely stained nuclei and fragmentation decreased significantly. CONCLUSIONS :β-boswellic acid can relieve oxygen-glucose deprivation induced injury of hippocampal neurons cells ,the mechanism of which may be associated with down-regulating the protein expression of cleaved caspase- 3 and Bax and up-regulating the protein expression of Bcl- 2.  
      关键词:β-boswellic acid;Hippocampal neurons cells;Oxygen-glucose deprivation;Cell apoptosis   
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    • WANG Zhongyuan,YANG Huali,CUI Xing,ZHU Gaofeng,TANG Lei,LIAO Weike
      Vol. 32, Issue 11, (2021)
      摘要:OBJECTIVE:To establish the metho d for the concentration det ermination of foretinib derivative LWK- 126 in liver microsomes,and to study its metabolism stability in liver microsomes of rats ,Beagle dogs and human. METHODS :In the in vitro incubation system of liver microsomes ,LWK-126 was dissolved in liver microsomal incubation systems of rats ,Beagle dog and human initiated by reduced nicotinamide adenine dinucleotide phosphate solution. After incubation in water at 37 ℃ for 0,5,10,20, 30 and 60 min,the reaction was terminated with acetonitrile containing internal standard (1 μg/mL tolbutamide). UPLC-MS/MS method was applied to determine the concentration of LWK- 126 in the incubation systems. The determination was performed on Waters BEH C 18 column with mobile phase consisted of water (containing 0.1% formic acid )-acetonitrile(containing 0.1% formic acid)by gradient elution at the flow rate of 0.4 mL/min. The column temperature was 30 ℃,and the sample size was 2 μL. The mass spectral analysis was performed in a positive electrospray ionization mode ,and the full MS experiment was run with the selective reaction monitoring mode with a scanning range of m/z 50→1 200. Taking the concentration of LWK- 126 at 0 min as reference,the remaining percentage and the enzyme kinetic parameters were calculated. RESULTS :The linear range of LWK- 126 was 0.05-15 μg/mL(R 2=0.999 2);the lower limit of quantification was 0.05 μg/mL,and the lowest detection limit was 0.01 μg/mL. The precision,accuracy,extraction recovery and matrix effect all met the analysis requirements of biological samples. The remaining percentage of LWK- 126 in liver microsomes of human ,rats and Beagle dogs for 60 min were (33.17±4.52)%,(3.14± 6.73)%,(1.38±5.85)%;t1/2 of them were 33.15,11.76,5.62 min;the clearance rates were 38.45,118.81,245.76 μL(/ min·mg), respectively. CONCLUSIONS :The method for the content ; determination of LWK- 126 in liver microsomes is established successfully. The order of metabolic stability of LWK- 126 in 〔2016〕4015) liver microsomes of different species is human >rats>Beagle dogs.  
        
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      发布时间:2022-06-21
    • HUANG Hai,ZHANG Yaowen,SONG Jiaxuan,YU Ming,XU Wankui
      Vol. 32, Issue 11, (2021)
      摘要:OBJECTIVE:To establish a m ethod to determine the cont ents of 20 elements impurities in Aminomethylbenzoic acid injection ,and to investigate its compatibility in low-borosilicate glass ampoules. METHODS :The sample was diluted with 5% nitric acid solution ,and then determined by ICP-MS using scandium ,indium and bismuth as internal standards. The nebulizer flow(argon)was 0.92 L/min,collision gas flow (helium)was 4.5 L/min,RF power was 1 895 W,plasma flow was 18 L/min, pump speed was 40 r/min,injection delay time was 65 s. The collision mode was used as measurement mode ,the data sampling adopted peak skipping mode ,and repeated for 3 times. The accelerated test was carried out after sample was stored at 70 ℃ for 1 and 3 months,and the compatibility was investigated by comparing the change trend of element impurity content. RESULTS :The linear range of vanadium ,cobalt,chromium,arsenic,cadmium,antimony,mercury,thallium and lead were 0.01-20 μg/L;those of magnesium ,aluminium,ferrum,nickel,copper,zinc,barium were 0.1-200 μg/L;those of boron ,silicon,potassium and calcium were 1-2 000 μg/L(r≥0.999 8). RSDs of precision ,intermediate precision ,stability(8 h)and repeatability test were all lower than 6%. The limits of quantitation were 0.000 7-2.986 3 μg/L;the limits of detection were 0.000 2-0.895 9 μg/L. The average recoveries were 88.50%-111.00%(RSDs were 0.52%-2.33%,n=9). The minimum content of 20 element impurities was less than detection limits ,the maximum contents were 3 835.9 μg/L(0 month),10 448.4 μg/L(1 month),17 261.2 μg/L(3 month) in Aminomethylbenzoic acid injection from 8 manufacturers. Among the 20 elements impurities ,except that boron , aluminum,magnesium,silicon,calcium and potassium were not specified ,the contents of other elements were less than the threshold. The research of compatibility showed that the impurity contents of seven elements such as boron ,aluminum,silicon, potassium,zinc,arsenic and barium showed an increasing trend. The silicon concentration ,silicon/aluminum concentration ratio and silicon/boron concentration ratio in the accelerated samples after stored for one and three months were significantly different from those stored for 0 month. CONCLUSIONS :The established method is sensitive ,reproducible and accurate ,and can be used for the content determination of 20 element impurities in Aminomethylbenzoic acid injection. The interaction between low-borosilicate ampoule and Aminomethylbenzoic acid injection is obvious.  
        
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      发布时间:2022-06-21
    • ZHANG Xiaodan,LI Wendi,ZHANG Ru,SHENG Jiejing,ZHANG Jianan,LIU Huiyu,LI Songlin
      Vol. 32, Issue 11, (2021)
      摘要:OBJECTIVE:To investigate the effects and mechanism of puerarin (Pue) on hypoxia-induced pyroptosis of pulmonary artery smooth muscle cells (PASMCs). METHODS :PASMCs of rats as research objects were randomly divided into normoxia group ,hypoxia group and hypoxia+Pue group (0.2 mmol/L). Except for normoxia group ,other groups were cultured with 5% CO2 and 3% O2 at 37 ℃ for 24 hours to establish hypoxia model. Western blot assay was used to detect the expression of pyroptosis related proteins [NOD-like receptor protein- 3 (NLPR3),caspase-1,interleukin-1 β (IL-1 β),apoptosis-associated speck-like protein (ASC)]. Lactate dehydrogenase (LDH)release assay was used to detect the release of LDH in cells ;Hoechst 33342/PI double staining test was adopted to detect the proportion of pyroptosis positive cells. PASMCs was randomly divided into normoxia group+control plasmid group ,hypoxia+control plasmid group ,hypoxia+over-expression plasmid group and hypoxia+ over-expression plasmid+Pue group. Except for the normoxia+control plasmid group ,the other groups were established hypoxia model by the same method. After transfection of control plasmid or NLRP 3 over-expression plasmid ,Western blot ,LDH release test and Hoechst 33342/PI double staining test were used to investigate whether Pue could inhibit hypoxia-induced PASMCs pyroptosis by interfering with the activity of NLRP 3 inflammasomes. RESULTS :Compared with normoxia group ,the expression of pyroptosis related proteins ,the release of LDH and the proportion of pyroptosis positive cells were increased significantly in hypoxia group (P<0.05 or P<0.01). Pue had the effect of reversing the above indexes (P<0.05 or P<0.01). When the NLRP 3 inflammasome was over-expressed ,the expression of pyroptosis related proteins ,the release of LDH and the proportion of Δ 基金项目:黑龙江省自然科学基金资助项目(No.ZD201416) pyroptosis positive cells were increased significantly (P<0.05 *教授,博士生导师 ,博士。研究方向 :心血管药理学 。电话: or P<0.01). Pue could inhibit the above phenomenon through 0451-58853046。E-mail:zhangxd85@163.com regulating NLRP 3 inflammasome (P<0.05 or P<0.01). 中国药房 2021年第32卷第11期 China Pharmacy 2021Vol. 32 No. 11 ·1337· CONCLUSIONS:Pue can significantly inhibit the hypoxia-induced pyroptosis of PASMCs by down-regulating the expression of pyroptosis related proteins ,reducing the release of LDH and proportion of pyroptosis positive cells. The mechanism is related to the activity inhibition of NLRP 3 inflammasome.  
      关键词:Puerarin;Pulmonary artery smooth muscle cells;Pyroptosis;NLRP3 inflammasome   
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      发布时间:2022-06-21
    • YU Xianhua,LIU Junling,JIN Chuanshan,ZHANG Yazhong,LI Jincai
      Vol. 32, Issue 11, (2021)
      摘要:OBJECTIVE:To establish the m ethod for simultaneous determination of 8 kinds of ginsenosides in Panax quinquefolium broken pieces. METHODS :HPLC-DAD method was used to determine the contents of ginsenoside Rg 1,Re,Rb1, Rc,Ro,Rb2,Rb3,Rd in P. quinquefolium broken pieces. The determination was performed on Agilent 5 TC-C18 column with mobile phase consisted of acetonitrile- 0.2% phosphoric acid water solution (gradient elution )at the flow rate of 1.0 mL/min. The column temperature was set at 30 ℃. The detection wavelength was set at 203 nm,and sample size was 10 μL. Ginsenoside Re and ginsenoside Rb 2 were used as control ,liner calibration with two-reference substances correction was used to predict the retention time of other 6 components,and was compared with the relative retention time method. Using ginsenoside Re as control , above components were quantified by the relative correction factor method ,and the results were compared with the external standard method. RESULTS :The contents of ginsenoside Rg 1,Re,Rb1,Rc,Ro,Rb2,Rb3,Rd were 10.59-12.78,2.160-2.768, 27.492-38.880,3.154-4.018,3.368-4.080,0.343-0.755,0.961-1.415,5.857-6.923 mg/g. The accuracy of two-reference substances linear correction method to predict the retention time of components was higher ,and the absolute deviation of the predicted retention time was lower than that of the relative retention time method. There was no significant difference between the relative correction factor method and the external standard method ,and relative error was <3% . CONCLUSIONS :Established two-reference substances for determination of multiple components can be used for qualitative and quantitative analysis of 8 kinds of ginsensides in P. quinquefolium broken pieces simultaneously and accurately.  
        
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    • LIU Guoqiang,KANG Shuo,WANG Xinchen
      Vol. 32, Issue 11, (2021)
      摘要:OBJECTIVE:To ev aluate the economics of pembrolizumab versus first-line chemotherapy in the treatment of advanced non-small cell lung cancer with high programmed cell death protein ligand 1(PD-L1)expression from the perspective of Chinese healthcare system. METHODS :Published KEYNOTE- 042 clinical trial data and relevant literature data were used to establish a Markov model to evaluate the economics of pembrolizumab versus first-line chemotherapy with a 20-years horizon and a 3-week cycle length ,discounting costs and utilities using a discount rate of 5%. One-way sensitivity analysis and probabilistic sensitivity analysis were used to evaluate the stability of the model results. RESULTS :The base-case results showed that pembrolizumab yield additional 1.62 QALYs more than first-line chemotherapy ,with an incremental cost of 54 648 yuan;the incremental cost-utility ratio was 33 686 yuan/QALY,which was lower than the willingness-to-pay threshold (WTP)in China. The results of one-way sensitivity analysis showed that the price of nivolumab ,the price of pembrolizumab and the proportion of patients who received second-line immunotherapy in first-line chemotherapy group had the greatest impact on the results. The results of probabilistic sensitivity analysis showed that the probability of pembrolizumab to be cost-effective gradually increased within the WTP of 0-140 000/QALY. When WTP was 70 892 yuan/QALY(one time of the per capita GDP of China in 2019),the probability of pembrolizumab to be cost-effective was 95%. When WTP beyond 100 000 yuan/QALY,the probability of pembrolizumab to be cost-effective was 100%. CONCLUSIONS :Pembrolizumab has economic advantages than first-line chemotherapy in the first-line treatment of non-small cell lung cancer with high PD-L 1 expression in China.  
        
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      发布时间:2022-06-21
    • ZHOU Lijuan,WU Zhenghua,WANG Shuowen,MIAO Wenqing,BAO Wuping,BAO Aihua,FAN Guorong
      Vol. 32, Issue 11, (2021)
      摘要:OBJECTIVE:To establish a method for concentration determination of anlotinib in human plasma and apply it in the clinic. METHODS :The plasma samples were pretreated by salting-out assisted with liquid-liquid extraction with ammonium acetate as salting out assistant and acetonitrile as solvent. Using voriconazole as internal standard ,LC-MS/MS method was adopted. The separation was performed on Waters X Bridge C 18 column with mobile phase consisting of 0.2% formic acid solution- acetonitrile(gradient elution )at the flow rate of 1 mL/min. The column temperature was set at 40 ℃,and sample size was 10 μL. The split ratio was 3∶7. The electrospray ion source and multiple reaction monitoring mode were used for the analysis. The ion pair of anlotinib and internal standard under positive ion mode were m/z 408.3→339.3 and m/z 350.2→281.3,respectively. RESULTS : Anlotinib showed a good linear relationship in the concentration range of 0.2-200 ng/mL(R2>0.996 7). The lowest limit of quantitation was 0.2 ng/mL. Intra-day and inter-day RSDs were no more than 12% (n=6 or n=3). Accuracies were 90.92%-108.00%(n=6 or n=3). The average extraction recoveries were 87.51%-100.00%(RSD<8%,n=6). The average matrix effects were 96.66%-99.93%(RSD<5%,n=6). The plasma concentration of 3 patients with NSCLC treated with anlotinib was 8.74-65.60 ng/mL. CONCLUSIONS :The method is simple ,accurate and specific ,and is suitable for the plasma concentration monitoring of anlotinib in NSCLC patients.  
      关键词:Anlotinib;LC-MS/MS;Salting-out assisted liquid-liquid extraction;Therapeutic drug monitoring   
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    • WANG Haikun,WANG Jie,WU Na,LI Cunming,LIN Ziwei,WU Wei
      Vol. 32, Issue 11, (2021)
      摘要:OBJECTIVE:To overview t he s ystematic revi ews on JAK inhibitors in the treatment of rheumatoid arthritis (RA), and to provide evidence-based basis for the treatment of RA with these drugs. METHODS :The Cochrane Library ,PubMed, Embase,CNKI,Wanfang database and VIP were electronically searched to collect systematic reviews of JAK inhibitors in the treatment of RA from inception to Dec. 2020. After data extraction of included systematic review ,PRISMA statement ,AMSTAR2 scale and GRADE were used to evaluate the report quality ,methodological quality and the level of evidence for outcome indicators. RESULTS :A total of 12 systematic reviews involving 103 outcomes were included. PRISMA score of systematic reviews was between 17.5 and 22.5,and the reported quality defects were mainly reflected in scheme ,registration and other aspects. AMSTAR 2 evaluation results showed that there were 6 studies of low quality and 6 studies of very low quality ,without high-quality study and medium-quality study. GRADE assessment results for outcome indicators showed low to medium quality of evidence. The summary of evidence showed that compared to placebo ,JAK inhibitor could alleviate various indicators of RA ; compared to adalimumab ,the advantage was not obvious. JAK inhibitors did not increase the incidence of serious adverse events , but the systematic reviews were inconsistent in their effects on the incidence of total adverse events and liver injury. CONCLUSIONS:The efficacy of JAK inhibitors in the treatment of RA has certain advantages over placebo ,but more studies are needed to demonstrate the efficacy of JAK inhibitors in the treatment of RA compared to other drugs ;the advantage of safety is uncertain.  
      关键词:JAK inhibitors;Rheumatoid arthritis;Overview of systematic reviews;Efficacy;Safety   
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      发布时间:2022-06-21
    • LI Liping,CHEN Dandan,CHEN Yunqiang,OUYANG Jiemiao
      Vol. 32, Issue 11, (2021)
      摘要:OBJECTIVE:To systematically evaluate the effectiveness and safety of nicorandil combined with atorvastatin calcium in the treatment of unstable angina pectoris ,and to provide reference for clinical treatment. METHODS :Retrieved from PubMed,Cochrane Library ,Embase database ,CBM,VIP,CNKI and Wanfang database ,randomized controlled trials (RCTs) about nicodil combined with atorvastatin calcium in the treatment of unstable angina pectoris were collected from the inception until Jan. 3rd,2021. The included studies were screened and evaluated with modified Jadad scale. Meta-analysis was performed by using Rev Man 5.3 software. RESULTS :A total of 10 RCTs were included ,involving 1 123 patients. Meta-analysis results showed that compared with atorvastatin calcium group ,nitcodil combined with atorvastatin calcium group significantly increased angina response rate [OR =3.44,95%CI(2.35,5.04),P<0.001],the rate of electrocardiogram improvement [OR =4.93,95%CI(2.88, 8.43),P<0.001],and significantly reduced MMP- 9 level [SMD =-4.21,95%CI(-4.63,-3.80),P<0.001],incidence of recurrent angina pectoris [OR =0.30,95%CI(0.12,0.71),P=0.006],myocardial infarction rate [OR =0.27,95%CI(0.08,0.89), P=0.03],the incidence of adverse cardiovascular events [OR =0.34,95% CI(0.21,0.55),P<0.001]. CONCLUSIONS : Nicorandil combined with atorvastatin calcium shows better efficacy in the treatment of unstable angina pectoris in terms of effective rate of angina pectoris ,improvement rate of cardiogram ,MMP-9 level,incidence of recurrent angina pectoris and the incidence of myocardial infarction ,and has better safety in the incidence of adverse cardiovascular events. Due to the limitation of included studies ,it remains to be verified by RCT with large sample,multi-center and high quality.  
        
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    • WANG Wanqing,HUANG Lifeng,ZHU Jianguo,CHEN Rong,HOU Xingyun,YI Jia,CHEN Wansheng
      Vol. 32, Issue 11, (2021)
      摘要:OBJECTIVE:To investi gate the role of clinical pharmacists in the treatment of delayed excretion of acute renal failure (ARF) with epileptic seizure caused by HD-MTX in a patient ,and to provide reference for rational drug use and pharmaceutical care in such type of patients. METHODS :A patient with diffuse large B-cell lymphoma was given HD-MTX for chemotherapy,and ARF caused by delayed methotrexate excretion occurred on the second day after methotrexate administration. Clinical physicians adjusted the rescue dose and frequency of calcium folinate but the effect was poor. Clinical pharmacists analyzed the causes of delayed methotrexate excretion by reviewing literature and combining with the patient ’s condition. It was suggested to monitor the blood concentration of methotrexate ,strengthen alkalization and hydration ,increase the volume of intravenous sodium bicarbonate from 125 mL to 250 mL,take Sodium bicarbonate tablets orally ,and monitor the pH value of urine (pH value of urine maintained above 7). In addition ,the pharmacist told the patient to drink water as much as possible to ensure the daily urine output reached 3 000 to 4 000 mL. The blood concentration of methotrexate was 16.14 μmol/L 44 h after administration ,which proved to be excretion delay. The patient had epileptic seizure on the 13th day after methotrexate medication. The physician gave sodium valproate 0.8 g intravenously to control epilepsy. The clinical pharmacist conducted pharmaceutical care for the patient ,and found that the compliance of the patient taking Sodium bicarbonate tablets and Sodium valproate tablets orally was not good ,so medication education and pharmaceutical care were conducted ,then the patient accepted and took the drugs on time. RESULTS : The physician adopted the suggestions of the pharmacist to monitor the blood concentration of methotrexate and performed symptomatic treatment. The urine volume of the patient increased ,the edema was reduced ,serum creatinine gradually returned to normal,and renal function recovered gradually ;the symptoms of epilepsy was controlled. CONCLUSIONS :In the treatment process of ARF complicated with epileptic seizure caused by excretion delay of HD-MTX ,the clinical pharmacist assisted physician to improve the treatment plan and conducted pharmaceutical care and medication education for the patient ,therefore ensure the safe and rational use of drugs .  
      关键词:HD-MTX;Central diffuse large B-cell lympHoma;Acute renal failure;Epileptic seizure;Pharmaceutical care   
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    • QIN Na,WU Xiaolong,ZHANG Hong
      Vol. 32, Issue 11, (2021)
      摘要:OBJECTIVE:To conduct the prescri ption comment of Chinese patent medicine based on self-developed rational drug use system and evaluate its effect ,and to promote rational use of Chinese patent medicine. METHODS :The self-developed rational drug use system was used to evaluate the complete prescriptions and classified special prescriptions of Chinese patent medicines in our hospital from Jan. to Jun. 2019(before implementation )and from Jan. to Jun. 2020(after implementation ); combined with pharmacists ’manual comments ,the situation of irrational drug use in the two periods was compared ,and the effect of prescription comment by rational drug use system was evaluated. RESULTS :Results of full prescription comment of Chinese patent medicine in our hospital showed that the unqualified rate of Chinese patent medicine prescriptions was 1.5%,which was significantly lower than 5.6% before the implementation (P<0.05). Results of special prescription comment of Chinese patent medicine showed that the unqualified rates of TCM injection ,toxic Chinese patent medicines and emergency Chinese patent medicines were 11.8%,10.7%,11.0% before implementation ;while after implementation ,they were 3.6%,4.2% and 6.6%, which were significantly lower than before implementation (P<0.05). CONCLUSIONS :Self-developed rational drug use system of Chinese patent medicine shows remarkable effect on full prescription comment and special comment ,which greatly improves the level of rational drug use of Chinese patent medicines in our hospital.  
      关键词:Chinese patent medicine;Rational drug use system;Prescription comment   
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    • PEI Pei,XU Huaifu
      Vol. 32, Issue 11, (2021)
      摘要:OBJECTIVE:To inve stigate the current situation of clinical pharmacists ’job stress and presenteeism behavior in tertiary hospitals of China and study their correlation. METHODS :Using the Brief Job Stress Questionnaire (BJSQ)and the presenteeism behavior individual questionnaire ,a survey of 623 clinical pharmacists in 311 tertiary hospitals from 31 provinces in China was conducted ;by establishing Logistic model between job stress ,its various dimensions (job demand ,job control , support)and presenteeism behavior ,the correlation analysis was performed for their survey results. RESULTS :The average job pressure of the interviewed clinical pharmacists was 36.75 points;the probability of presenteeism behavior was 20.38%. Logistic regression model analysis results showed that job stress and its two dimensions (job demand ,job control )had a significant positive correlation with presenteeism behavior (P<0.05). CONCLUSIONS :The job stress of clinical pharmacists in tertiary hospitals in my country is relatively high ,which is also the main reason for their presenteeism behavior. Job stress can be reduced (such as increasing the staffing appropriately ,providing reasonable rest time ,improving the job substitution of clinical pharmacists )to reduce the prevalence of presenteeism behavior.  
      关键词:Job stress;Presenteeism;Clinical pharmacist   
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