最新刊期
      卷 32 ， 期 18 ， 2021
      • HAN Xinyue,NIE Hongtao
        Vol. 32, Issue 18, (2021)
        摘要：OBJECTIVE：To provide reference for constructing a patent linking system in line with international standards and balancing the interest conflict between original drug enterprises and generic drug enterprises. METHODS ：The relevant supporting systems of patent link in the United States were introduced ；combined with the development status and relevant systems of drug patent protection at home and abroad ，the existing problems of China ’s drug patent management system were analyzed to put forward suggestions for improvement. RESULTS & CONCLUSIONS ：The United States patent linking system included Orange book system ，generic drug patent declaration system ，generic drug approval waiting period and market monopoly period system of the first generic drug. The innovation and accessibility in the field of pharmaceutical products were facing the dilemma of “commons tragedy ”and“anti commons tragedy ”. There were many problems in China ’s drug patent protection ，such as insufficient R&D and innovation ability inhibited the development of the pharmaceutical industry ，imperfect laws and regulations were not conducive to the settlement of medical professional disputes. It is suggested to establish a digital information database of patented drugs ，standardize the existing generic drug patent declaration system ，promote the coordination between patent litigation cycle and approval waiting period ，increase the independent innovation ability of the pharmaceutical industry ，promote the coordination between pharmaceutical innovation and drug accessibility ，and jointly promote the improvement of intellectual property legislation and the development of medical and health undertakings.  
        关键词：Drug patent;Innovation;Accessibility;Interest balance;Original drugs;Generic drugs;Patent linking system   
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        发布时间：2022-06-21
      • WU Yingqi,ZHANG Shengyu,YIN Tong,WU Zhangbao,ZHU Bin,SHEN Aizong
        Vol. 32, Issue 18, (2021)
        摘要：OBJECTIVE：To prov ide reference for mobilizing the work enthusiasm of clinical pharmacists ，and further promoting the strategic objectives of performance appraisal in three-level public hospitals （“National examination ”for short ）. METHODS：A department performance appraisal team was established ，and a key performance indicator system consisting of 4 first-level indicators and 9 second-level indicators was constructed by using literature retrieval and expert consultation. The performance distribution method of double assessment of performance score and performance score was established ，and a performance publicity and feedback performance mechanism was formed. Relevant data were collected to compare the core work indicators of clinical pharmacists ，use intensity of antibiotics ，compliance rate of essential drugs in our hospital from Apr. to Dec. 2019（before implementation ）and Apr. to Dec. 2020（after implementation ）. RESULTS ：After the implementation of performance appraisal scheme ，the total number of medication recommendations of clinical pharmacists increased from 1 192 to 5 226，with an increase of 338.42％；the number of medication suggestions received increased from 846 to 4 855，with an increase of 473.88％； and the rate of drug suggestions received increased from 70.97％ to 92.90％；the number of pharmaceutical consultation increased from 195 to 1 284，with an increase of 558.46％；the number of drug counseling increased from 1 203 to 2 719，increasing by 126.02％. Form Apr. to Dec. 2020，the number of patient safety medication evaluation forms reached 660. The antibiotics use density（AUD）in clinical departments of 13 clinical pharmacists were decreased to different extent after the implementation of performance appraisal scheme ，the decine rate was 92.31％（12/13），and the compliance rate was 69.23％（9/13）；utilization rate of essential medicine among outpatients of 11 clinical pharmacists ’clinical departments had achieved positive growth ，and those among inpatients of 2 clinical pharmacists ’clinical departments had achieved positive growth. CONCLUSIONS ：The performance appraisal system of clinical pharm acists formulated by our hospital links the “National examination ”index with the performance ， appraisal of clinical pharmacists ，which can provide ideas for No.2018sxzx57，No.2020jyxm2328，No.2020jyxm2307） the performance appraisal of three-level public hospitals and help to promote the high-quality and sustainable development of hospital pharmaceutical care.  
          
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        发布时间：2022-06-21
      • ZHAO Yuxin,SUN Bingzhe,NI Weixing,LIANG Ranzhi,DI Bin,SU Mengxiang
        Vol. 32, Issue 18, (2021)
        摘要：OBJECTIVE：To establish a method for the content determination of potential genotoxic impurity maleic hydrazide in azintamide raw material. METHODS ：HPLC-FLD method was adopted. The determination was performed on Thermo Syncronis C18 column with mobile phase consisted of 0.2 mol/L acetic acid-methanol （gradient elution ）. The column temperature was set at 30 ℃，the excitation wavelength was 315 nm and emission wavelength was 389 nm. The flow rate was 1 mL/min，and the sample size was 20 μL. RESULTS：The blank solvent and azintamide did not interfere with the determination of maleic hydrazide. The linear range of maleic hydrazide was 19.5-300 ng/mL（r＝0.999 9）. The limit of detection was 4.5 ng/mL and the limit of quantification was 19.5 ng/mL. The recovery ranged from 98.79％ to 103.76％（RSDs were lower than 3.00％，n＝9）. RSDs of precision and stability （24 h）tests were no more than 5.63％，and those of durability tests were less than 2.00％（n＝6）. Maleic hydrazide was not detected in 3 batches of azinamide raw material. CONCLUSIONS ：The method is specific ，sensitive and accurate. It can be used for the trace determination of maleic hydrazide in azintamide or other matrix.  
        关键词：Maleic hydrazide;Azintamide;HPLC-FLD;Genotoxic impurity   
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        发布时间：2022-06-21
      • LI Yuxin,XING Na,ZHANG Zhihong,YU Tianying,MA Enyao,WANG Xue,BAI Haodong,ZENG Yuanning,WANG Qiuhong
        Vol. 32, Issue 18, (2021)
        摘要：OBJECTIVE：To identify Panax notoginseng and its processed products . METHODS ：The fingerprint was established by HPLC. Using ginsenoside Rb 1 as reference ，HPLC fingerprints of 15 batches of P. notoginseng and its processed products were drawn and the similarity evaluation was conducted by using the Similarity Evaluation System for TCM Chromatographic Fingerprints（2012 edition）. The common peaks were confirmed by comparing with substance control. SPSS 21.0 and SIMCA 14.1 software were used to perform cluster analysis ，principal component analysis and orthogonal partial least squares-discriminant analysis；taking the variable importance projection （VIP）value greater than 1 as the standard ，the differential marker components causing the quality difference between P. notoginseng and its processed products were screened. IR fingerprints of P. notoginseng and its processed products were established by OMNIC 8.2.0 software，and the spectral similarity was evaluated ；double index sequence analysis was used to analyze absorption peaks of IR fingerprints of 15 batches of P. notoginseng and its processed products. RESULTS ：There were 16 common peaks in the fingerprints of 15 batches of P. notoginseng ， and the similarities were 0.911-1.000；there were 25 common peaks in the fingerprints of processed products ，and the similaritieswere 0.862-1.000. They had 12 identical common peaks ，and wang668@sina.com three of them were ident ified as sanchinoside R 1，ginsenoside Rg1 and ginsenoside Rb 1. Results of cluster analysi s showed that when the distance was 10，15 batches of P. notoginseng could be clustered into two categories ，SW1-SW5 into one category ，SH1-SH5 and SQ 1-SQ5 into one category ，ZW1-ZW5，ZH1-ZH5 and ZQ1-ZQ5 of 15 batches of processed products could be clustered into one category. When the distance was 5，15 batches of P. notoginseng could be clustered into three categories ，SW1-SW5 into one category ，SH2-SH5 and SQ 2 into one category ，SQ1， SQ3-SQ5 and SH 1 into one category. Fifteen batches of processed products could be clustered into two categories ，ZW1-ZW5 into one category ，ZH1-ZH5 and ZQ 1-ZQ5 into one category. The results of principal component analysis showed that the cumulative variance contribution rate of the first two principal components was 80.104％ . The results of orthogonal partial least squares-discriminant analysis showed that the VIP values of the five peaks were greater than 1，which were peak H ，peak G ，peak J，peak F （ginsenoside Rg 1）and peak I. The similarity of IR fingerprints of 15 batches of P. notoginseng and its processed products were 0.889 7-1.000 0 and 0.972 8-1.000 0；the common peak rates were 80％-100％，and the variation peak rates were 0-17.65％ and 0-18.75％，respectively. By comparing the wave numbers of absorption peaks ，it was found that there were differences between P. notoginseng at 3 440 and 1 450 cm－1 and processed products at 1 530 and 575 cm－1. CONCLUSIONS ：Established HPLC fingerprint and IR fingerprint have good similarity ，and could effectively distinguish P. notoginseng and its processed products. P. notoginseng and its processed products from different habitats have high common peak rate and low variation rate ，and their chemical components are different ；peak H ，peak G ，peak J ，ginsenoside Rg 1 and peak I are differential marker components causing the quality difference between P. notoginseng and processed products.  
        关键词：Panax notoginseng;Processed products;HPLC;IR spectrum;Different habitats   
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        发布时间：2022-06-21
      • ZHANG Lixin,YU Xiaocong,WANG Zekun,MAO Chunqin,SHU Yachun
        Vol. 32, Issue 18, (2021)
        摘要：OBJECTIVE：To esta blish the m ethod for identifying Schizonepeta tenusfolia from different habitats based on odor information. METHODS ：The odor of S. tenusfolia from different habitats were identified by Heracles Ⅱ ultra-fast gas phase electronic nose. Qualitative analysis was conducted according to obtained chromatographic information combined with AroChemBase database and Kovats retention index qualitative database. Principle component analysis （PCA）and discriminant factor analysis （DFA）were conducted by using Alpha Soft V 14.2 software，and cluster analysis （CA）was performed with SPSS 22.2 software. RESULTS ：There were 16 common peaks in 15 batches of S. tenusfolia from different habitats. After comparison with AroChemBase database and Kovates retention index qualitative database ，a total of 13 possible components were obtained. The possible components and sensory description information of S. tenusfolia from different habitats were basically the same ，but only the content was different. The chromatographic peak intensities of common peak No. 2 were in descending order as Anhui ＞ Gansu＞Henan＞Hebei＞Jiangsu，the chromatographic peak intensities of common peak No. 6 were in descending order as Anhui ＞ Hebei＞Gansu≈Henan＞Jiangsu，the chromatographic peak intensities of common peak No. 9 were in descending order as Anhui ＞ Gansu＞Henan＞Jiangsu＞Hebei，the chromatographic peak intensity of common peak No. 13 were in descending order as Anhui ≈ Gansu＞Hebei＞Jiangsu＞Henan，which represented the chromatographic peak intensity of methyl formate （peak No. 2），α-pinene （peak No. 6），3-nonone（peak No. 9）and α-terpineol（peak No. 13）were significantly different due to the change of habitats. PCA results showed that the cumulative contribution rate of the first two principal components was 96.807％. Results of DFA showed that contribution rates of discriminant factor 1 and discriminant factor 2 were 92.089％ and 3.982％. CA results showed that when the distance was 10，15 batches of samples could be clustered into 3 categories，B1-B5 and J 1-J3 into one category ，A1-A3 into one category ，G1，G2，N1 and N 2 into one category. The results were basically consistent with those of PCA and DFA. CONCLUSIONS：Ultra-fast gas phase electronic nose technology can be used to identify S. tenusfolia from different habitats rapidly. Methyl formate ，α-pinene，3-nonone and α-terpineol may be the key factors to distinguish S. tenusfolia from different habitats.  
          
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        发布时间：2022-06-21
      • LIU Xudong,ZHAO Liang,CAO Xuefeng,HU Jie
        Vol. 32, Issue 18, (2021)
        摘要：OBJECTIVE：To study th e effects of dexmedetomidine on ventricular arrhythmia in myocardial hypertrophy model rabbits and the expression of calcium ion /calmodulin-dependent protein kinase Ⅱ（CaMKⅡ）in myocardial tissue of rabbits. METHODS： The rabbits were randomly divided into sham operation group ， model group ， dexmedetomidine low-dose ， medium-dose and high-dose groups （10，25，50 μ g/kg），CaMK Ⅱ inhibitor KN- 93 group （10 mg/kg），high-dose of dexmedetomidine+KN-93 group（50 μg/kg+10 mg/kg），with 10 rabbits in each group. Except for the sham operation group ，other groups received abdominal aortic coarctation to induce myocardial hypertrophy model. After surgery ，administration groups were given relevant dose of dexmedetomidine or/and intraperitoneal injection of KN- 93；sham operation group and model group were given constant volume of normal saline intravenously ，once every other day ，for consecutive 8 weeks. After last medication ， programmed stimulation was used to induce ventricular arrhythmia. The induction rate of early posterior depolarization （EAD）and tip torsion type ventricular tachycardia （Tdp）were recorded. Left ventricular ejection fraction （LVEF）and left ventricular shortener fraction（FS）were measured. QT interval ，transventricular wall repolarization dispersion （TDR）and transmembrane 90％ action potential duration （APD90）of endocardial and epicardial cardiomyocytes in wedge-shaped myocardium were recorded. The ratio of heart weight to body weight （HW/BW）and the thickness of left ventricular wall （LVT）were measured and calculated. The cross-sectional area of cardiomyocytes ，mRNA expression of ANP and BNP as well as protein expression of CaMK Ⅱ and p-CaMK Ⅱ in myocardial tissue was measured. RESULTS ：Compared with sham operation group ，the induction rate of EAD and Tdp ，HW/BM， LVT，mRNA expression of ANP and BNP and protein relative expression of CaMK Ⅱ and p-CaMK Ⅱ in cardiac tissue were all increased significantly ，while LVEF and FS were decreased significantly ；QT interval ，APD90 of endocardial and epicardial cardiomyocytes were all prolonged significantly ；TDR was increased significantly ，while cross-sectional area of cardiomyocytes was increased significantly in model group （P＜0.05）. Compared with model group ，induction rate of EAD and Tdp ，HW/BW （except for dexmedetomidine low-dose group ），LVT（except for dexmedetomidine low-dose group ），mRNA relative expression of ANP（except for dexmedetomidine low-dose group ）and BNP （except for dexmedetomidine low-dose group ）as well as protein relative expression of CaMK Ⅱ and p-CaMK Ⅱ were all decreased significantly in administration groups ；the levels of LVEF （except for dexmedetomidine low-dose group ） and FS （except for dexmedetomidine low-dose group ） were all increased significantly； QT interval ，APD90 of endocardial and epicardial cardiomyocytes were shortened significantly ； TDR and cross-sectional area of cardiomyocytes （except for dexmedetomidine low-dose group ）were decreased significantly （P＜0.05）；the improvement effects of dexmedetomidine high-dose group were significantly better than those of dexmedetomidine low-dose and medium-dose groups （P＜0.05）. Compared with dexmedetomidine high-dose group and KN- 93 group，the improvement of above indexes were all more significant in high-dose of dexmedetomidine+KN- 93 group（P＜0.05）. CONCLUSIONS ：Dexmedetomidine can reduce the induction rate of ventricular arrhythmia and improve myocardial hypertrophy in myocardial hypertrophy model rabbits，the mechanism of which may be associated with down-regulation of CaMK Ⅱ expression.  
        关键词：Dexmedetomidine;Myocardial hypertrop hy;Ventricular arrhythmia;CaMKⅡ;Rabbit   
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        发布时间：2022-06-21
      • PENG Shuang,YANG Haiyuan,ZHANG Minjuan,WEI Wenzhi
        Vol. 32, Issue 18, (2021)
        摘要：OBJECTIVE：To es tablish a method for the content determination of heavy metals [lead （Pb），cadmium（Cd）， copper （Cu）， mercury （Hg）] and harmful elements [arsenic （As）] in Pediatric paracetamol artificial cow-bezoar and chlorphenamine maleate granules. METHODS ：The samples were conducted pretreatment by microwave digestion instrument and determined by inductively coupled plasma mass spectrometry （ICP-MS）using elements germanium ，indium，bismuth as internal standard. RESULTS ：The linear ranges of Pb ，As，Cu，Cd and Hg were 1-20，0.5-10，5-100，0.5-10 and 0.2-4 ng/mL， respectively （all r＞0.997）. The limits of detection （LODs） were 0.041 1，0.013 2，0.057 3，0.009 0，0.005 4 ng/mL， respectively. The limits of quantification （LOQs）were 0.137 0，0.044 0，0.191 0，0.030 0，0.018 0 ng/mL，respectively. RSDs of precision and repeatability tests were all less than 6％. RSDs of stability tests （28 h）of Pb ，As，Cu and Cd were all less than 5％， and that of stability test （28 h）of Hg was less than 7％. The average recoveries were 89.44％（RSD＝5.87％，n＝9），99.56％ （RSD＝5.46％ ，n＝9），96.12％（RSD＝4.62％ ，n＝9），105.82％（RSD＝2.80％ ，n＝9）and 90.23％（RSD＝3.59％ ，n＝9）， respectively. Five elements were all detected in 63 batches of samples ，and the contents of them were 0.191 0-1.527 6，0.002 5- 0.047 4，0.034 1-1.549 0，0.001 5-0.078 8 and 0.001 9-0.005 4 mg/kg，respectively. CONCLUSIONS ：The method is simple ， sensitive and accurate. It is suitable for simultaneous determination of 5 elements in Pediatric paracetamol artificial cow-bezoar and chlorphenamine maleate granules.  
          
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        发布时间：2022-06-21
      • LI Yuanyuan,WANG Wei,JU Chengguo,JIA Tianzhu
        Vol. 32, Issue 18, (2021)
        摘要：OBJECTIVE：To establish the microwave processing technology of yellow wine-processed Curculigo orchioides ， and compare it with traditional technology. METHODS ：HPLC method was adopted to determine the contents of curculigoside ， orcinol glucoside and orcinol gentiobioside in C. orchioides . Based on the single factor tests ，microwave processing technology was optimized and validated with orthogonal test combined with comprehensive weighted scoring method ，with the amount of yellow wine，microwave power ，wetting time and microwave time as factors ，using the contents of curculigoside ，orcinol glucoside ， orcinol gentiobioside and ethanol soluble extract as the indexes. The contents of C. orchioides decoction pieces and processed products were compared. RESULTS ：The optimal microwave processing technology included that the amount of yellow wine was 20％（the weight of C. orchioides decoction pieces was 20％），microwave power was 300 W，wetting time was 3 h，microwave time was 2 min. After 3 times of validation tests ，average contents of curculigoside，orcinol glucoside ，orcinol gentiobioside and ethanol soluble extract were 0.095 6％，0.723 9％，0.406 6％，10.115 3％，and RSD were 0.71％，0.54％，0.99％，1.44％（n＝3）. Average comprehensive score were 99.08（RSD＝0.69％，n＝3）. Except for the content of ethanol soluble extract in traditional wine-processed product ，the contents of curculigoside and orcinol gentiobioside in traditional wine-processed product and microwave processed product as well as the content of ethanol soluble extract in microwave processed product were all significantly higher than C. orchioides decoction pieces ；the contents of curculigoside and orcinol gentiobioside in microwave processed product were both significantly higher than traditional wine-processed product （P＜0.05）. The contents of orcinol glucoside in 2 processed product were significantly lower than C. orchioides decoction pieces ，while the microwave processed product was significantly higher than traditional wine-processed product （P＜0.05）. CONCLUSIONS ：Optimized microwave processing technology is stable and feasible ，and can be used for the processing of yellow wine-processed C. orchioides .  
        关键词：Yellow wine-processed Curculigo orchioides;Microwave processing technology;HPLC;Orthogonal test;Content   
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        发布时间：2022-06-21
      • HE Ling,TANG Jian,PENG Zhongtian
        Vol. 32, Issue 18, (2021)
        摘要：OBJECTIVE：To prelimi narily investigate the possible mechanism of orazamide to prevent anti-tuberculosis drug-induced liver injury （ATB-DILI）. METHODS ：A total of 60 Kunming mice were randomly divided into blank group ，model group，positive control group [diammonium glycyrrhizinate 60 mg/（kg·d）]，orazamide low-dose ，medium-dose and high-dose groups [ 80，160，320 mg/（kg·d）]，with 10 mice in each group. Except for blank group ，other groups were given isoniazid [ 75 mg/（kg·d）]+rifampicin [ 75 mg/（kg·d）] for 14 days intragastrically to induce ATB-DILI model. At the same time ，administration groups were given relevant medicine intragastrically ，blank group and model group were given normal saline intragastrically. The administration volume was 20 mL/（kg·d），once a day ，for consecutive 14 days. The general conditions of the mice were observed and recorded every day ，such as growth and development ，mental and diet state. After last medication ，liver index was calculated ， and HE staining was adopted to observe pathological changes of liver tissue of mice. The positive expression of high mobility group protein B 1 （HMGB1） and NF-κ B in liver tissue were detected by streptavidin biotin-peroxidase complex （SABC） immuno- histochemistry. The serum levels of liver function indexes in serum ，the protein expression of advanced glycation end product receptor（RAGE）and TNF-α in liver tissue were detected by ELISA. RESULTS：Compared with blank group ，the growth and development of mice in the model group were slow ，and their appetite and spirit were poor. The liver index ，serum levels of TBIL ， DBIL，ALT，AST，ALP，TBA and γ-GT were increased significantly （P＜0.05）. Structural disorder of liver lobules ，degeneration and necrosis of liver cells and inflammatory cell infiltration were observed. The expression of HMGB 1，NF-κB，RAGE and TNF-α in liver tissue were elevated significantly （P＜0.05）. Compared with model group ，the general condition of mice were all improved to different extents in orazamide low-dose ，medium-dose and high-dose groups ，positive control group ，while liver index and above serum indexes were all decreased significantly （P＜0.05）. The pathological changes of liver tissue were all improved to different extents ，while the protein expression of HMGB 1，NF-κB，RAGE and TNF-α were all decreased significantly（P＜0.05）. The improvement of above indexes in orazamide high-dose group were all significantly better than orazamide low-dose and medium-dose groups （P＜0.05）；the levels of ALP and TBA in orazamide high-dose group were significantly lower than positive control group （P＜0.05）. CONCLUSIONS ：Orazamide can prevent ATB-DILI induced by isoniazid combined with rifampicin in mice，the mechanism of which may be associated with down-regulating the protein expression of HMGB 1 and RAGE in liver tissue and inhibiting the secretion of inflammatory factors.  
        关键词：Orazamide;Anti-tuberculosis drug-induced liver injury;HMGB1-RAGE signaling pathway;Mice   
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        发布时间：2022-06-21
      • GU Lixia,FU Yongmei,ZHANG Shu,LIN Juyi,DENG Hong,LU Yongmei
        Vol. 32, Issue 18, (2021)
        摘要：OBJECTIVE： To e stablish modified aqueous two-phase extraction （ATPE） system of polyphenols from Archidendron clypearia. METHODS ：Taking the polyphenol content ，extraction efficiency and partition coefficient of A. clypearia as indexes ，the solid-liquid ratio ，ethanol mass fraction and ultrasonic time of ATPE system were selected by single factor tests . The aqueous two-phase extracts from different polar parts of A. clypearia was prepared. The modifier was selected by taking polyphenol content and antioxidant activity [IC 50 of 1，1-diphenyl-2-trinitrophenylhydrazine （DPPH）， 2，2′-hydrazine bis （3-ethylbenzothiazole-6-sulfonic acid ） diammonium salt （ABTS）] as indicators ，combined with the grey correlation analysis between polyphenols and antioxidant activity. The effects of modified ATPE system with different mass fraction （0-90％）of modifier on the extraction of polyphenols from A. clypearia were investigated and compared with traditional extraction technology （ultrasonic extraction and heating reflux extraction ）. RESULTS ：The optimal ATPE system included solid-liquid ratio of 1 ∶ 45， ethanol mass fraction of 40％，（NH4）2SO4 mass fraction of 11％，ultrasonic extraction time of 20 min，at room temperature. In 3 validation tests ，polyphenol content ，extraction efficiency and partition coefficient were （28.35±1.01）％（RSD＝3.56％，n＝3）， （98.87±0.19）％（RSD＝0.19％，n＝3）and 13.25±0.71（RSD＝5.39％，n＝3），respectively. The modifier was ethyl acetate. When the mass fraction of ethyl acetate in the ethyl acetate-ethanol mixed solvent was 70％，there was no significant difference in the content and anti-oxidant activity of polyphenols from A. clypearia of modified ATPE （P＞0.05）. The yield and transfer rate of it were si gnificantly higher than those of ultrasonic extraction and heating reflux extraction （P＜0.05）. CONCLUSIONS ：The modified ATPE system with better extraction yield and transfer rate than the traditional extraction technology is successfully established，which can extract polyphenols from A. clypearia 1048214903@qq.com in one step.  
          
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        发布时间：2022-06-21
      • GUAN Xin,WANG Luying,LI Hongchao
        Vol. 32, Issue 18, (2021)
        摘要：OBJECTIVE：To pr ovide reference for the future pharmacoeconomic evaluation. METHODS ：Four typical cases of pharmacoeconomic evaluation showed the special situation that “not cost-effective at a zero price ”，defined the concept of “net value”to assist in theoretical analysis ，and summarized the possible causes of this situation . RESULTS & CONCLUSIONS ：The system（ATPS）：an overview and advances in its applica background treatment cost other than the target drug was too high ，the patient ’s quality of life during survival was too low ，the threshold of willingness to pay of incremental cost-effectiveness ratio was too low ，the cost of risk events during extended survival was too high or the health loss was too high ，and the price of the control scheme was too low ，which might affect the results of economic evaluation ，and even le d to the dilemma of pharmacoeconomic evaluation of “not cost-effective at a zero price ”. Pharmacoeconomic evaluation discusses the economy of intervention programs rather than the economy of drugs. The uneconomic results caused by various reasons need to be treated objectively ；theoretically，all“relevant”and“irrelevant”costs should be included in the calculation category in pharmacoeconomic evaluation ；pharmacoeconomics mainly solves the problem of “cost performance”comparison among several treatment schemes ，and the medical and health field often needs to face problems such as ethics and fairness. Therefore ，researchers may need to jump out of the framework of pharmacoeconomics analysis and conduct in-depth discussion from a higher and broader perspective.  
        关键词：Pharmacoeconomics;Not cost-effective at a zero price;Background therapy;Cost;Cause analysis   
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        发布时间：2022-06-21
      • LIU Shenglan,TANG Zhi,CHEN Lei,WU Sufen,ZHOU Ling,LIAO Yinjuan,ZHANG Jie
        Vol. 32, Issue 18, (2021)
        摘要：OBJECTIVE ：To est ablish the method for the determination of 20（S）-protopanaxadiol（PPD）concentration in human plasma. METHODS ：Plasma samples were precipitated with acetonitrile and determined by UPLC-MS/MS ，using finandrogen as internal standard. The determination was performed on Waters ACQUITY UPLC HSS T 3 column with mobile phase consisted of 5 mmol/L ammonium bicarbonate aqueous solution-acetonitrile （gradient elution ）at the flow rate of 0.4 mL/min. The column temperature was set at 40 ℃，and sample size was 10 μL. The ion source was electrospray ion source，and negative ion scanning was carried out with multiple reaction monitoring mode . The ion pairs used for quantitative analysis were m/z 459.40→ 375.20（PPD）and m/z 371.30→315.30（internal standard ）. At the same time ，the method was applied to the determination of clinical samples. RESULTS ：The linear range of PPD was 0.25-30.00 ng/mL（r＝0.999 2），and the limit of quantitation was 0.25 ng/mL. RSDs of intra-batch and inter-batch were all lower than 10％，and relative errors （RE）were －14.61％-12.69％. Extraction method and matrix effect did not affect the quantitative determination of PPD. In ginsenoside CK 100 mg group ，ginsenoside CK 200 mg group and ginsenoside CK 300 mg group ，mean cmax of patients with rheumatoid arthritis after oral administration of corresponding drugs were 18.06，30.03，27.00 ng/mL；median tmax were 12.0，6.0，12.0 h；mean AUC 0-t were 622.52，668.15， 1 155.97 ng·h/mL. CONCLUTIONS ：The method for the determination of PPD concentration in human plasma is successfully established. The method is sensitive ，accurate， kq1907011） stable，easy to operate and less plasma consumption. It can be used for the quantitative determination of clinical samples.  
          
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      • TAO Guanghua,WU Yong,GE Huashun,YU Buwei
        Vol. 32, Issue 18, (2021)
        摘要：OBJECTIVE：To investigate the effects of lidocaine aerosol inhalation on perioperative pulmonary function ， inflammation factor and related complications of patients with one-lung ventilation. METHODS ：A total of 120 patients who were admitted to the Affiliated Hospital of Panzhihua University from January 2018 to May 2020 and planned to undergo partial pneumonectomy under general anesthesia and one-lung ventilation were selected. According to random number table method ，they were divided into lidocaine aerosol inhalation group （group L ）and sterile water aerosol inhalation group （group N ），with 60 cases in each group. Two groups were given Midazolam injection 0.1 mg/kg+Propofol injectable emulsion 2.0 mg/kg+Sufentanil citrate injection 0.4 μg/kg to induce anesthesia. After the insertion of the double-lumen tracheal tube ，group L was given aerosol inhalation of Lidocaine hydrochloride injection 1.5 mg/kg diluted to 20 mL with sterile water ；group N was given aerosol inhalation of sterile water 20 mL at the flow rate of 2 L/min. Patients in both groups were continuously pumped with Propofol injectable emulsion 4-12 mg/（kg·h）+Remifentanil hydrochloride for injection 0.2-1 μg（/ kg·min）+Cisatracurium besilate for injection 0.05-0.1 mg/（kg·h）for anesthesia maintenance. Eight hours after operation ，group L inhaled of Lidocaine hydrochloride injection 1.5 mg/kg diluted to 20 mL with sterile water again ，and group N inhaled of sterile water 20 mL again. Arterial blood gas analysis indexes [arterial partial pressure of oxygen （PaO2），partial pressure of carbon dioxide （PaCO2），lactic acid （Lac），oxygenation index （P/F）]，serum inflammatory factors [interleukin 6 （IL-6），tumor necrosis factor α（TNF-α）and nuclear factor κB（NF-κB）] were observed in 2 groups before anesthesia（T1），60 min of one-lung ventilation （T2），and 12 h after extubation （T3）. Respiratory and circulatory parameters [extravascular lung water（EVLW），pulmonary vascular permeability index （PVPI），heart rate （HR），stroke volume （SV）] were also observed 5 min after anesthesia （t1），T2 and 15 min after surgery （t3）. Extubation time ，visual analogue scale （VAS） score of 12 h after extubation，time of getting out of bed ，the incidence of throat pain of 12 h after extubation and the occurrence of ADR were recorded in 2 groups. RESULTS ：There was no significant difference in arterial blood gas analysis indexes ，serum inflammatory factor levels ，respiratory and circulatory parameters between the two groups at T 1 or t 1（P＞0.05）. The levels of PaO 2，PaCO2， Lac，IL-6，TNF-α and NF-κB in 2 groups at T 2 and T 3 were significantly higher than at T 1，P/F at T 2 and T 3 was significantly lower than at T 1；in group L ，the levels of PaCO 2，Lac，IL-6，TNF-α，NF-κB were significantly lower than group N，and PaO 2 and P/F were significantly higher than group N （P＜0.05）. EVLW and PVPI of 2 groups at T 2and t 3，SV of group L ，HR of group N were significantly higher than corresponding group at T 1，while EVLW ，PVPI and HR of group L were significantly lower than group N，SV was significantly higher than group N at corresponding period （P＜0.05）. The extubation time ，VAS score of 12 h after extubation，time to get out of bed after surgery ，the incidence of throat pain of 12 h after extubation in group L were significantly shorter or lower than group N （P＜0.05）. No obvious and serious ADR occurred during recovery. CONCLUSIONS：Lidocaine aerosol inhalation can effectively improve ventilation and oxygenation function of patients undergoing one-lung ventilation ，inhibit the release of inflammatory factors ，and reduce the incidence of postoperative complications with good safety.  
          
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      • ZHEN Lulu,LIU Lu,LIU Chang,YAN Meixing
        Vol. 32, Issue 18, (2021)
        摘要：OBJECTIVE：To systematically evaluate the safety of meropenem for neonatal infection ，and to provide evidence-based reference for safe use of it in the neonatal population. METHODS ：Retrieved from PubMed ，Embase，Cochrane Library，ISI Web of Science ，International Health Technology Assessment Network Website ，China Journal Full-text Database ， Wanfang Database ，CBM，Chinese Sci-tech Periodical Full-text Database ，randomized controlled trials （RCTs）about meropenem or meropenem combined other drugs （trial group ）versus the similar drugs that could replace meropenem （control group ）for neonatal infection were collected during the inception to May 1st，2021. After literature screening and data extraction ，the quality of included literatures were evaluated with Cochrane systematically evaluator manual 5.1.0. Meta-analysis was conducted with RevMan 5.3 software. RESULTS ：A total of 25 RCTs were included ，involving 2 090 children. Results of Meta-analysis showed that the incidence of overall ADR in trial group was significantly lower than control group [RR ＝0.53，95％CI（0.44，0.65），P＜0.000 01]. Results of subgroup analysis showed that the incidence of overall ADR in trial group was significantly lower than control group receiving ceftazidime [RR ＝0.55，95％CI（0.41，0.74），P＜0.000 1]，tigecycline [RR ＝0.37，95％CI（0.23，0.59），P＜0.000 1]， ceftriaxone [RR ＝0.53，95％CI（0.35，0.80），P＝0.003]. The incidence of overall ADR in trial group with neonatal purulent meningitis [RR ＝0.63，95％CI（0.44，0.92），P＝0.02]，severe neonatal multidrug-resistant bacterial infection [RR ＝0.37，95％CI（0.25， 0.55），P＜0.000 01]，neonatal severe bacterial infection [RR ＝ 0.67，95％CI（0.48，0.94），P＝0.02] were significantly lower than control group. The incidence of specific ADR such as mail： rash，gastrointestinal reaction ，hemoglobin reduction in trialgroup were significantly lower than control group （P＜0.05）. There was no statistical significance in the incidence of specific ADR between 2 groups，such as elevated transaminase ，secondary fungal infection and renal injury （P＞0.05）. Results of bias analysis showed that when the incidence of overall ADR was used as index ，there was a certain degree of publication bias in this study ，when the incidence of specific ADR was used as index ，there was less possibility of publication bias in this study. CONCLUSIONS：Meropenem is safe in the treatment of neonatal infection ，especially in the treatment of neonatal purulent meningitis，severe neonatal multidrug-resistant bacterial infection and neonatal severe bacterial infection ，it is superior to ceftazidime，tigecycline，ceftriaxone and other antibacterial drugs in safety.  
        关键词：Meropenem;Newborn;Infection;Safety;Meta-analysis   
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      • YANG Ping,AN Wei
        Vol. 32, Issue 18, (2021)
        摘要：OBJECTIVE：To provide reference for safe use of Nicotinic acid injection in the clinic. METHODS ：The clinical pharmacist introduced the occurrence and treatment of cerebral infarction secondary to anaphylactic shock caused by Nicotinic acid injection in a patient with hypertension in the cardiovascular medicine department of our hospital. By consulting the relevant drug instructions and searching the relevant literatures ，the inducement and severity of ADR were evaluated ，and the rational drug use suggestions of Nicotinic acid injection were put forward. RESULTS & CONCLUSIONS ：According to the Management Measures for ADR Reporting and Monitoring ，the correlation between anaphylactic shock and Nicotinic acid injection was analyzed and evaluated as “very likely ”. Secondary cerebral infarction was mainly associated with a variety of risk factors （hypertension， hyperlipidemia，etc.），among which there was a greater possibility of secondary cerebral infarction due to insufficient cerebral perfusion caused by anaphylactic shock and sharp drop of blood pressure. The above symptoms could be life-threatening if not rescued in time ，which was defined as “severe ADR ”. Clinical pharmacists suggest that when using Nicotinic acid injection ，the patient’s allergy history should be inquired in detail ，the use should be started from a small dose ，and the patient ’s reaction should be closely monitored in the early stage of medication. For patients with high-risk factors of cerebrovascular diseases （hypertension， hyperlipidemia，etc.），if anaphylactic shock occurs ，the effective circulating blood volume should be restored as soon as possible. After the blood pressure rises ，drugs such as improving microcirculation can be used to prevent secondary cerebral infarction. Clinical pharmacists should timely carry out medication education for such patients ，and warn patients to inform doctors of the related drugs with severe ADR in the later stage of treatment ，so as to prevent the recurrence of anaphylactic shock and severe complications. At the same time ，when antihypertensive drugs and statins are combined ，the blood pressure monitoring and the monitoring of ADR such as muscle toxicity should be strengthened，so as to ensure the medication safety of patients.  
          
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      • MA Zhuyue,GU Jie,YUAN Hongyu
        Vol. 32, Issue 18, (2021)
        摘要：OBJECTIVE：To provide r eference for optimizing the review rules of PASS system and improving rational drug use in our hospital. METHODS ：The prescription review of Calcineurin inhibitor （CNI）was taken as an example. The pharmacists of our hospital collected the inappropriate rules in PASS system in their daily work ，and modified and improved them. Three thousands outpatient prescriptions and inpatient orders containing CNI in the fourth quarter of 2019（before the rule modification ） and the fourth quarter of 2020（after the rule modification ）were randomly selected for our hospital. The warnings ，false positives and false negatives of PASS system review were compared before and after rule modification. RESULTS ：There were some problems in the PASS system of our hospital ，such as too strict judgement on off-label use ，lax review rules ，false positive in the audit of contraindications ，failure to grade warnings according to the severity of drug interactions ，inaccurate judgment of patients ’ liver and kidney function ，lengthy problem description ，incomplete or wrong information in the system database ，lack of effects information of food and traditional Chinese medicine on CNI ，etc. In view of these inappropriate rules ，the pharmacy department of our hospital improved the quality of PASS system review rules through formulating the standardized management process of off-label use ， reasonably enabling the interception function of PASS system ， modifying the false-positive rules of drug contraindications，warning drug interaction by grade ，reviewing in combination with laboratory test reports ，and real-time maintenance of system database information and adding patient education content. The number of warning had decreased from 182 to 105，and the proportion of false-negative and false-positive review results from 25.03％ to 0.43％ after a year of optimization. CONCLUSIONS：The optimization of CNI review rules can enhance the applicability of the PASS system ，facilitate the advance of the prescription pre-review ，and promote clinical rational drug use.  
        关键词：PASS system;Pre-review;Calcineurin inhibitor;Review rules;Rational drug use   
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      • XIA Lu,HUANG Yuankai,XI Xiaoyu
        Vol. 32, Issue 18, (2021)
        摘要：OBJECTIVE：To summarize the current output research status of collaboration between clinical pharmacists and physicians in China ，and to provide reference for comprehensively understanding the development trend of relevant research and the collaborative value of clinical pharmacists and physicians. METHODS ：Literature analysis was used to sort out the general characteristics，the indexes and results of output related researches ，and investigate the focuses and results of collaboration output indexes from 3 dimensions，such as time ，hospital level and disease type /situation. RESULTS & CONCLUSIONS ：In the aspect of focuses，the number of output related researches in China had decreased in recent years ，among which tertiary hospitals conducted more related researches ；secondary hospitals had few related researches and a limited perspective on evaluating outputs. On the whole，the current researches paid more attention to t he use of antibiotics in bacterial in fection. Most of the research sites were inpatient departments ，and most of the research designs were historical controlled parallel trials and single arm trials. In addition，the three output measurement indexes of safety ， cpulucyxia@163.com effectiveness and economy develop diversely ， scientifically and comprehensively. Ho wever，at the present ，little attention was paid to complex and dif ficult measurement indexes ，such as“cognitive level of patients ”“recurrence rate ”improvement in “quality of life ”“cost-effectiveness/benefit analysis of clinical pharmaceutical care ”. In aspect of research result ，most of the existing researches could prove that the collaboration can significantly improve medication safety ，effectiveness and economy ；the proportion of “significantly improved ”results of most indicators had been stable or had increased stage by stage. However ，there were still a small number of researches that had not carried out statistical test on the results before and after collaboration. In the future ，relevant researchers still need to strengthen the research on outpatient pharmaceutical care ，randomized controlled trials and multi disease and multi situation ，and should scientifically and reasonably select output measurement indicators and pay attention to the application of statistical methods ，so as to further expand the focus of research and comprehensively explore the value of collaboration between clinical pharmacists and physicians.  
          
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