最新刊期
      卷 34 ， 期 1 ， 2023
      • XU Gan,LUO Weihua,SONG Haibo
        Vol. 34, Issue 1, Pages: 1-6(2023) DOI: 10.6039/j.issn.1001-0408.2023.01.01
        摘要：OBJECTIVETo provide reference for improving the classification management of prescription drugs and nonprescriptiondrugs in China by learning from the classification management system of prescription drugs and non-prescription drugs in Canada.METHODSThe content and experience of classification management system of prescription drugs and non-prescription drugs in Canada were analyzed， and the thinking of the classification management of prescription drugs and non-prescription drugs in China was proposed.RESULTS & CONCLUSIONSAccording to the classification of prescription drugs and non-prescription drugs， drugs can be divided into class Ⅰ drugs， class Ⅱ drugs， class Ⅲ drugs， unclassified drugs in Canada. Specific evaluation factors and management requirements have been established for drug classification. Canada has established a set of systematic management systems and technical standards， which has reference value for improving the classification management system in China. It is suggested to further improve the drug classification management system and supporting policies， strengthen fine classification management of prescription drugs and non-prescription drugs and improve classification registration and transformation review standards in China， by learning from Canadian prescription drug and non-prescription drug system and management model.  
        关键词：non-prescription drug;drug classification management;Canada   
        13
        |
        7
        |
        0
        <HTML>
        <L-PDF><WORD><Meta-XML>
        <引用本文> <批量引用> 33161670 false
        发布时间：2023-02-22
      • JIANG Feng,TIAN Kan
        Vol. 34, Issue 1, Pages: 7-11(2023) DOI: 10.6039/j.issn.1001-0408.2023.01.02
        摘要：OBJECTIVETo study the variety included in the List of Overseas New Drugs Urgently Needed in Clinic in China and optimization strategy， in order to better meet the needs of patients.METHODSThe release process of List of Overseas New Drugs Urgently Needed in Clinic， the characteristics and attributes of the new drugs urgently needed abroad， and the problems in the implementation process were all analyzed to put forward some suggestions for optimizing the List of Overseas New Drugs Urgently Needed in Clinic. RESULTS & CONCLUSIONSThe release process of the List of Overseas New Drugs Urgently Needed in Clinic was roughly divided into incubation stage， preparation stage and implementation stage. The treatment fields of 3 batches of overseas new drugs urgently needed in clinic were relatively concentrated on endocrine and metabolic diseases，tumor and skin diseases. Of included 73 varieties， 50 varieties have been approved for market，and 26 varieties have been included in the medical insurance， 4 varieties were included in the Catalogue of Encouraged Generic Drugs. At present， there are still some problems in our country， such as the shortage monitoring system needs to be established and improved； the linkage with medical insurance is weakened； the encouragement of generic drugs is insufficient. It is necessary to strengthen the cooperation of monitored departments in the shortage of new overseas drugs，establish a medical insurance payment system oriented by clinical value， and improve the incentive mechanism to encourage the imitation of overseas new drugs urgently needed in clinic.  
        关键词：variety;optimization strategy   
        8
        |
        1
        |
        0
        <HTML>
        <L-PDF><WORD><Meta-XML>
        <引用本文> <批量引用> 33162051 false
        发布时间：2023-02-22
      • CHU Shuang,WU Yanrao,WU Limin,CUI Zhenghao,WANG Pan,SUN Yiran,XIE Zhishen,ZHANG Zhenqiang
        Vol. 34, Issue 1, Pages: 12-17(2023) DOI: 10.6039/j.issn.1001-0408.2023.01.03
        摘要：OBJECTIVETo explore the effect mechanism of ethanol extract from Atractylodes macrocephala （EEAM） on microglial phagocytosis and degradation of amyloid β （Aβ） based on peroxisome proliferator-activated receptor γ （PPAR-γ） signaling pathway.METHODSTaking neuromicroglial cell BV2 as subjects， confocal microscopy was used to observe the effects of EEAM （0.3， 0.4， 0.5 mg/mL， similarly hereinafter） on phagocytosis and degradation of Aβ in microglia. Human embryonic kidney cell HEK293 was used to investigate the effects of EEAM on luciferase transcriptional activity of PPAR-γ. The effect of EEAM on nuclear translocation of PPAR-γ was investigated by immunofluorescence. Alzheimer’s disease BV2 cell model was induced by Aβ1-42， and quantitative polymerase chain reaction was used to investigate the effects of EEAM on mRNA expressions of PPAR-γ downstream target genes （Lxra， Lxrb， Abca1， Abcg1， Cd36， Sra and Apoe）.RESULTSThe results of Aβ uptake experiment showed that after the intervention of medium and high doses of EEAM， fluorescence intensity of Aβ in BV2 cells increased significantly （P＜0.05）. The degradation experiment of Aβ showed that after the intervention of medium and high doses of EEAM， fluorescence intensity of Aβ in BV2 cells decreased significantly （P＜0.05）. After the intervention of different doses of EEAM， luciferase transcriptional activity of PPAR-γ in HEK293 cells increased significantly （P＜0.05）； fluorescence intensity of PPAR-γ in BV2 cells and nuclei （except for low-dose group） increased significantly （P＜0.05）. mRNA expressions of Lxra， Lxrb， Abca1， Abcg1， Cd36， Sra and Apoe in BV2 cells were increased significantly （P＜0.05）.CONCLUSIONSEEAM can promote the uptake and degradation of Aβ in microglia by activating PPAR-γ signaling pathway， thus improving Alzheimer’s disease.  
        关键词：PPAR-γ;microglia;amyloid β;Alzheimer’s disease   
        7
        |
        0
        |
        0
        <HTML>
        <L-PDF><WORD><Meta-XML>
        <引用本文> <批量引用> 33162035 false
        发布时间：2023-02-22
      • WAN Anping,ZHANG Jing,ZHOU Xiong,FENG Yulin,LIU Jun,HE Yao,LI Xiang
        Vol. 34, Issue 1, Pages: 18-22(2023) DOI: 10.6039/j.issn.1001-0408.2023.01.04
        摘要：OBJECTIVETo prepare anemoside B4 （AB4） and programmed cell death ligand 1 （PDL1） siRNA （siP） co-delivered cRGD-modified targeting liposomes （AB4/siP-c-L）， and to study the cellular uptake in vitro.METHODSThe cRGD-modified AB4-loaded targeted liposomes （AB4-c-L） were prepared by ethanol injection. AB4-c-L was mixed with 20 nmol/L siP in the same volume and AB4/siP-c-L was obtained through electrostatic adsorption. The particle size， Zeta potential， morphology， encapsulation efficiency and drug content， in vitro release behavior and serum stability of AB4/siP-c-L were investigated by laser scattering particle size tester， transmission electron microscopy， ultrafiltration centrifugation， dialysis and agar-gel electrophoresis block test. Cellular uptake of AB4/siP-c-L by Lewis lung cancer cells LLC and its intracellular localization were evaluated by flow cytometry and confocal laser scan technique.RESULTSThe average particle size of AB4/siP-c-L was （187.4±3.1） nm， and the Zeta potential was （33.5±1.4） mV. AB4/siP-c-L was spheroidal in shape. The encapsulation efficiency and content of AB4 were （95.2±0.4） % and （1.0±0.2） mg/mL， respectively. AB4/siP-c-L could better package siP， and exhibited good serum stability， obvious pH sensitivity and sustained release property. The uptake rate of AB4/siP-c-L by LLC cells was significantly higher than that of free drug， and was able to accumulate in cytoplasm.CONCLUSIONSAB4/siP-c-L can effectively realize the co-loading of AB4 and gene drug siP， which has certain in vitro targeting to LLC cells.  
        关键词：PD-L1;siRNA;liposome;cellular uptake   
        7
        |
        1
        |
        0
        <HTML>
        <L-PDF><WORD><Meta-XML>
        <引用本文> <批量引用> 33161961 false
        发布时间：2023-02-22
      • LIAO Taiyang,ZHANG Li,YANG Nan,WEI Yibao,LYU Jingxian,XU Bo,DING Liang,WANG Peimin,ZHANG Li
        Vol. 34, Issue 1, Pages: 23-28(2023) DOI: 10.6039/j.issn.1001-0408.2023.01.05
        摘要：OBJECTIVETo investigate the improvement effect mechanism of Xibining prescription （XBN） on knee osteoarthritis （KOA） model rats based on AMP-activated protein kinase（AMPK）/mammalian target of rapamycin （mTOR） signaling pathway.METHODSTotally 36 rats were randomly divided into blank group， model group， XBN group （12.56 g/kg）， XBN+metformin （AMPK agonist） group （12.56 g/kg XBN+100 mg/kg metformin）， with 9 rats in each group. Except for blank group， KOA model was induced by anterior cruciate ligament transection in other groups. After modeling， each group was given relevant medicine/normal saline， XBN and normal saline intragastrically， once a day， and metformin intraperitoneally， every other day， for 4 consecutive weeks. The pathomorphological changes of cartilage tissue in rats were observed and Mankin scoring was conducted. The expression level of Aggrecan in rat cartilage， mRNA and protein expressions of platelet reactive protein disintegrin and metalloproteinase with thrombospondin motifs 4 （ADAMTS-4）， ADAMTS-5， matrix metalloproteinase 3 （MMP-3） and MMP-13， and the phosphorylation level of AMPK and mTOR proteins were detected.RESULTSCompared with blank group， the structure of cartilage tissue in the model group was disordered， the matrix of cartilage layer was lightly stained， the tide line was distorted or interrupted， and Mankin score was significantly increased （P＜0.05）. The protein expression of Aggrecan in cartilage tissue and the phosphorylation level of AMPK protein were all decreased significantly （P＜0.05）； mRNA and protein expressions of ADAMTS-4， ADAMTS-5， MMP-3 and MMP-13 and the phosphorylation levels of mTOR protein were significantly increased in cartilage tissues （P＜0.05）. Compared with model group， the pathological morphology of cartilage was improved significantly in each administration group， and above score or indexes were reversed significantly （P＜0.05）. Compared with XBN group， the degree of cartilage lesions in rats was further alleviated in XBN+ metformin group， and the levels of above score or indicators were further improved （P＜0.05）.CONCLUSIONSXBN can ameliorate cartilage injury in KOA model rats， promote cartilage synthesis and reduce cartilage degradation， the mechanism of which may be associated with activating AMPK/mTOR signaling pathway.  
        关键词：knee osteoarthritis;AMP-activated protein kinase;mammalian target of rapamycin;cartilage   
        9
        |
        2
        |
        0
        <HTML>
        <L-PDF><WORD><Meta-XML>
        <引用本文> <批量引用> 33162107 false
        发布时间：2023-02-22
      • LI Qian,CHEN Xiangming,CHANG Xinxin,CUI Wenhua,LI Yang,XUE Zijing,ZHENG Yuguang,SONG Junna
        Vol. 34, Issue 1, Pages: 29-33(2023) DOI: 10.6039/j.issn.1001-0408.2023.01.06
        摘要：OBJECTIVETo provide reference for clarifying improvement effects of Anemarrhena asphodeloides on sepsis-induced myocardial injury and potential material basis.METHODSWater extract of A. asphodeloides was extracted by thermal reflux method. Total xanthone and total saponins in A. asphodeloides were separated by macroporous adsorption resin. The mice model of sepsis-induced myocardial injury was established by intraperitoneal injection of lipopolysaccharide. The effects of the location of three extraction fractions and the monomers of A. asphodeloides as mangiferin， timosaponin AⅢ and timosaponin BⅡ on the survival rate of the model mice were explored. HE staining was used to observe the effects of mangiferin， timosaponin AⅢ and timosaponin BⅡ on myocardial morphology in model mice. The effects of mangiferin on mRNA expressions of inflammatory cytokines [interleukin-6 （IL-6）， IL-1β and tumor necrosis factor-α （TNF-α）] and the level of reactive oxygen species （ROS） in myocardial tissue of model mice were detected.RESULTSCompared with the model group， the survival rate of mice in the intervention group of total xanthone， total saponins and water extract was increased to different extents， especially total xanthone fraction. Mangiferin， timosaponin AⅢ and timosaponin BⅡcould improve the degree of myocardial cell swelling and muscle bundle arrangement disorder in model mice， especially mangiferin. Compared with model group， mRNA expressions of IL-6， IL-1β and TNF-α， ROS level in myocardium of mice after mangiferin intervention were decreased to different extents.CONCLUSIONSThe different extraction fractions of A. asphodeloides can improve survival rate of mice with sepsis-induced myocardial injury， especially total xanthone fraction. Mangiferin is the best among the three monomers of A. asphodeloides to improve sepsis-induced myocardial injury， which may play a role in anti-sepsis myocardial injury by anti-inflammation and antioxidantion.  
        关键词：total xanthone;total saponins;active ingredients;mangiferin;sepsis-induced myocardial injury   
        6
        |
        0
        |
        0
        <HTML>
        <L-PDF><WORD><Meta-XML>
        <引用本文> <批量引用> 33162117 false
        发布时间：2023-02-22
      • YANG Chaokun,XU Shijuan,XU Wenfen,SUN Qingwen,WANG Bo,GUO Jiangtao,ZHANG Yongping
        Vol. 34, Issue 1, Pages: 34-39(2023) DOI: 10.6039/j.issn.1001-0408.2023.01.07
        摘要：OBJECTIVETo provide reference for quality control of Gentiana rhodantha.METHODSTaking 52 batches of G. rhodantha as subject， ultra-high performance liquid chromatography （UPLC） fingerprint was adopted. The similarity of 52 batches of medicinal materials samples was evaluated by the Similarity Evaluation System for Chromatographic Fingerprints of Traditional Chinese Medicine （2004A edition）； the content of mangiferin was determined； chemometric analyses [cluster analysis， principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA）] were performed.RESULTSUPLC fingerprints of 52 batches of G. rhodantha were established， 17 common peaks were identified， and 6 of them were identified， which were loganic acid （peak 1）， neomangiferin （peak 3）， swertiamarin （peak 5）， dangyin （peak 6）， mangiferin （peak 7） and isoorientin （peak 9）. The similarities of 52 batches of medicinal materials samples were all greater than 0.9； cluster analysis showed that S1-S46， S48-S52 clustered into one class， and S47 alone； PCA results showed that the cumulative variance contribution rate of the first six principal components was 82.928%； OPLS-DA results showed that the corresponding components of swertiamarin， mangiferin and chemical composition represented by peak 4， 14， 15， 16 were the main iconic components affecting the quality differences of G. rhodantha medicinal materials. The contents of mangiferin in 52 batches of medicinal material samples ranged from 18.2 to 101.0 mg/g， mostly in accordance with 2020 edition of Chinese Pharmacopoeia.CONCLUSIONSThe established UPLC fingerprint and chemometric analysis methods combined with content determination method of mangiferin can comprehensively evaluate the quality of G. rhodantha.  
        关键词：fingerprint;ultra-high performance liquid chromatography;cluster analysis;principal component analysis;orthogonal partial least square-discriminant analysis;mangiferin   
        13
        |
        3
        |
        0
        <HTML>
        <L-PDF><WORD><Meta-XML>
        <引用本文> <批量引用> 33162149 false
        发布时间：2023-02-22
      • GONG Baihui,YUE Dongfang,LI Caixia,GUAN Min,LI Yongfang
        Vol. 34, Issue 1, Pages: 40-46(2023) DOI: 10.6039/j.issn.1001-0408.2023.01.08
        摘要：OBJECTIVETo study the protective mechanism of Bawei chenxiang powder containing serum on H9c2 cells injured by oxygen-glucose deprivation （OGD）.METHODSH9c2 cells were divided into blank group， model group and Bawei chenxiang powder low-dose， medium-dose and high-dose groups （the dose of drug containing serum 2.5， 8， 12 g/kg）. H9c2 cells were cultured in vitro to establish OGD model. After intervention with drug-containing serum， survival rate of cell was detected. The cell morphology was observed； the levels of lactate dehydrogenase （LDH）， creatine kinase （CK）， superoxide dismutase （SOD）， catalase （CAT）， respiratory chain complexⅠ （ComplexⅠ）， glutathione peroxidase （GSH-Px） and malondialdehyde （MDA） were detected. The contents of reactive oxygen species （ROS）， mitochondrial membrane potential and apoptosis were also detected. The expressions of oxidative stress-related proteins [Kelch ECH association protein 1 （Keap1）， nuclear factor erythroid 2-related factor 2 （Nrf2）， heme oxygenase 1 （HO-1）， NADH oxidoreductase coenzyme 10 （Ndufa10）， thioredoxin （Trx）] and apoptosis-related proteins [B-cell lymphoma 2 （Bcl-2）， Bcl-2 associated X protein （Bax）， Caspase-3 and cytochrome C （Cytc）] were detected.RESULTSCompared with blank group， the cell morphology of model group was damaged； the levels of LDH， CK and MDA were significantly increased （P＜0.01）， while the levels of CAT， ComplexⅠ， SOD and GSH-Px and mitochondrial membrane potential were significantly decreased （P＜0.01）. The content of intracellular ROS and apoptotic rate were significantly increased （P＜0.01）； the expressions of oxidative stress-related proteins （Keap1， Nrf2， HO-1， Ndufa10 and Trx） and pro-apoptosis proteins （Bax， Caspase-3 and Cytc） were significantly increased （P＜0.05）， while the expression of anti-apoptotic protein Bcl-2 was significantly decreased （P＜0.05）. After administration of Bawei chenxiang powder containing serum， the cell morphology improved， and most of the above indexes were significantly reversed （P＜0.05 or P＜0.01）.CONCLUSIONSBawei chenxiang powder containing serum has a good protective effect on H9c2 cells damaged by OGD， the mechanism of which is related to the reduction of oxidative damage and inhibition of cell apoptosis.  
        关键词：myocardial ischemia;oxygen-glucose deprivation;oxidative stress;cell apoptosis   
        5
        |
        0
        |
        0
        <HTML>
        <L-PDF><WORD><Meta-XML>
        <引用本文> <批量引用> 33161808 false
        发布时间：2023-02-22
      • WEI Xuenai,YANG Kun,LIU Qin,ZHAO Peng,YAN Ying,LI Yanmei
        Vol. 34, Issue 1, Pages: 47-51(2023) DOI: 10.6039/j.issn.1001-0408.2023.01.09
        摘要：OBJECTIVETo investigate the inhibitory effect of natural compound XCQ-9 of Cynanchum paniculatum on the proliferation and apoptosis of Jurkat cell line of human T-cell acute lymphoblastic leukemia and its possible mechanism.METHODSJurkat cell was used as the leukemia cell model， and MTT assay was adopted to detect the inhibitory effects of 0（blank control）， 2.5， 5， 10， 20 and 40 μmol/L XCQ-9 on the proliferation of Jurkat cell after treated for 24， 48， 72 h. After treated with 0 （blank control）， 2.5， 5， 10 μmol/L XCQ-9 for 24 h and 48 h， the cell cycle and apoptosis were analyzed by flow cytometry. The expressions of Caspase-9， Cleaved Caspase-9， Caspase-3， Cleaved Caspase-3， poly ADP-ribose poly-merase （PARP）， Cleaved-PARP， cyclin-dependent kinase 1 （CDK1） and Cyclin B1 were detected by Western blot after treated for 24 h.RESULTSCompared with blank control group， XCQ-9 at different concentrations could significantly decrease the survival rate of Jurkat cells （P＜0.01）， and showed a dose and time-dependent manner. After 48 h treatment of 5， 10 μmol/L XCQ-9， Jurkat cell apoptosis was induced significantly （P＜0.05 or P＜0.01）， and the cell was arrested in G2 phase （P＜0.01）. After 24 h treatment of 10 μmol/L XCQ-9， the protein expressions of CDK1 and Caspase-9 were remarkably down-regulated （P＜0.01）， while the protein expressions of Cyclin B1， Cleaved Caspase-9， Cleaved Caspase-3 and Cleaved PARP were significantly up-regulated （P＜0.05 or P＜0.01）.CONCLUSIONSXCQ-9 plays anti-tumor effect through inducing G2 phase arrest to inhibit proliferation and activating Caspase pathway to increase apoptosis.  
        关键词：Cynanchum paniculatum;human T-cell acute lymphoblastic leukemia;Jurkat cell;cell apoptosis;cell cycle;Caspase pathway   
        7
        |
        3
        |
        0
        <HTML>
        <L-PDF><WORD><Meta-XML>
        <引用本文> <批量引用> 33162248 false
        发布时间：2023-02-22
      • DUAN Yuqing,ZHU Tianmi,CHEN Shuhe,DUAN Xueyun,WANG Simeng
        Vol. 34, Issue 1, Pages: 52-56(2023) DOI: 10.6039/j.issn.1001-0408.2023.01.10
        摘要：OBJECTIVETo establish thin-layer chromatography （TLC） identification method and high-performance liquid chromatography （HPLC） fingerprint of Inonotus obliquus， and to evaluate the quality of I. obliquus by chemical pattern recognition.METHODSTLC method was used to identify trametenolic acid and inotodiol in I. obliquus qualitatively. HPLC fingerprint of I. obliquus was established； Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine （2012 edition） was used to determine the common peaks and evaluate the similarity； chemical pattern recognition analysis [cluster analysis， principal component analysis and orthogonal partial least squares-discriminant analysis （OPLS-DA）] of 22 batches of I. obliquus was performed with SPSS 23.0 software and SIMCA14.1 software.RESULTSIn the TLC， the same color spots were found at the same position in the chromatograms of test sample and substance control. A total of 10 common peaks were marked in the HPLC fingerprints of 22 batches of I. obliquus， with similarities of 0.942-0.995. No. 3 peak was identified as trametenolic acid， No.4 peak as inotodiol， No. 9 peak as ergosterol and No. 10 peak as lanosterol. Results of cluster analysis showed that S1-S15， S19， S21 and S22 could be clustered into the first category， and S16-S18 and S20 were clustered into the second category. Results of principal component analysis showed that top 4 samples in the list of comprehensive score were S17， S18， S16 and S20. Results of OPLS-DA showed that three marking components that may affect the quality of I. obliquus were screened according to the standard of VIP＞1， i.e. No. 4 peak （inotodiol， VIP value of 1.86）， No. 3 peak （trametenolic acid， VIP value of 1.62） and No. 7 peak （VIP value of 1.27）.CONCLUSIONSThis study establishes TLC method and HPLC fingerprint of I. obliquus successfully， which can provide reference for the quality control of I. obliquus by combining with chemical pattern recognition.  
        关键词：thin-layer chromatography;fingerprint;high-performance liquid chromatography;chemical pattern recognition   
        7
        |
        1
        |
        0
        <HTML>
        <L-PDF><WORD><Meta-XML>
        <引用本文> <批量引用> 33161764 false
        发布时间：2023-02-22
      • WANG Dandan,NING Meng,WU Zuomin,WANG Rui,JIN Shaoju,YU Xiaotao
        Vol. 34, Issue 1, Pages: 57-61(2023) DOI: 10.6039/j.issn.1001-0408.2023.01.11
        摘要：OBJECTIVETo optimize extraction technology of couplet medicinals of Astragalus membranaceus-Puerariae lobatae.METHODSWith contents of puerarin，daidzin，calycosin-7-O-β-D-glucopyranoside，daidzein，calycosin and formononetin and the yield of dry extract as index，the analytic hierarchy method was used to determine the weight coefficient of each index and calculate the comprehensive score. The effects of solid-liquid ratio， extraction times and extraction time on the comprehensive score were investigated by single factor test. The level of each factor was determined. By multi-index comprehensive scoring method， using comprehensive scores of above 7 indexes as indexes，the extraction technology of couplet medicinals of A. membranaceus-P. lobata was optimized by orthogonal experiment，and the validation tests were conducted.RESULTSThe weight coefficient for the contents of puerarin，daidzin，calycosin-7-O-β-D-glucopyranoside，daidzein，calycosin and formononetin and the yield of dry extract were respectively 0.304 7，0.065 2，0.185 8，0.185 8，0.107 8，0.107 8 and 0.042 7. The optimal extraction technology was determined as follows： solid-liquid of 1∶8（g/mL），extracting 3 times and for 1 h each time. RSD of each evaluation index in the validation test results was lower than 3.00% （n＝3）.CONCLUSIONSThe optimized extraction technology for A. membranaceus-P. lobata is stable and feasible.  
        关键词：extraction technology;multi-index comprehensive scoring method;orthogonal experiment;puerarin;daidzin;calycosin-7-O-β-D-glucopyranoside;daidzein;calycosin;formononetin   
        13
        |
        3
        |
        0
        <HTML>
        <L-PDF><WORD><Meta-XML>
        <引用本文> <批量引用> 33161727 false
        发布时间：2023-02-22
      • PANG Qianqian,YUE Weiye,LIU Keqin,TANG Jianhua
        Vol. 34, Issue 1, Pages: 62-66(2023) DOI: 10.6039/j.issn.1001-0408.2023.01.12
        摘要：OBJECTIVETo determine the contents of 11 components in Xueli zhike syrup， establish its chemometric method and provide reference for its quality control.METHODSHPLC method was established to simultaneously determine the contents of amygdalin， deapi-platycoside E， platycoside E， platycodin D3， euscaphic acid， tormentic acid， maslinic acid， corosolic acid， praeruptorin A， praeruptorin B and praeruptorin E in 12 batches of Xueli zhike syrup. The quality evaluation of 12 batches of samples was performed by chemometrics.RESULTSThe 11 components had good linear relationships within their respective ranges （r≥0.999 1）； RSDs of precision， reproducibility and stability （24 h） tests were all lower than 2.00%. The average recovery rates ranged 96.90%-100.01% （RSDs were all lower than 2.00%）. Cluster analysis showed that 12 batches of samples were clustered into 3 groups. Principal component analysis showed that the first two principal components could represent 88.53% information of 11 components in Xueli zhike syrup. Partial least squares-discrimination analysis showed that euscaphic acid， amygdalin and praeruptorin A were the main potential markers affecting the quality of Xueli zhike syrup.CONCLUSIONSThe established method can be used to control the quality of Xueli zhike syrup.  
        关键词：HPLC;chemometric;multi-index;quality control;euscaphic acid;amygdalin;praeruptorin A   
        12
        |
        3
        |
        0
        <HTML>
        <L-PDF><WORD><Meta-XML>
        <引用本文> <批量引用> 33162204 false
        发布时间：2023-02-22
      • WU Lei,LIU Yuping,LU Chao,SHU Yachun
        Vol. 34, Issue 1, Pages: 67-71(2023) DOI: 10.6039/j.issn.1001-0408.2023.01.13
        摘要：OBJECTIVETo compare the change law of multi-components in the extraction process between Liuwei dihuang powder decoction pieces and traditional decoction pieces （hereinafter referred to as powder decoction pieces and traditional decoction pieces）， and to provide scientific basis for the modern technology research of Liuwei dihuang formula.METHODSTaking powder decoction pieces and traditional decoction pieces as samples， the samples were taken when soaking for 60 min， at 0， 5， 10， 15， 20， 25， 30， 40， 50， 60 min of the first decocting and at 5， 10， 20， 30， 40 min of the second decocting， respectively. HPLC method was used to establish the fingerprints of 2 kinds of decoction pieces with different decocting time. The similarity evaluation and peak identification were performed. The contents of 8 components including 5-hydroxyfurfural， catechin， monoglycoside， loganin， swertin glycoside， dihydroquercetin， paeonol and benzoyl paeoniflorin were all determined.RESULTSWith different decocting time， the similarties between 2 kinds of decoction pieces and their respective control fingerprints R were all greater than 0.98. In the fingerprints of traditional decoction pieces， five chromatographic peaks were identified， namely， 5-hydroxyfurfural， monetin， swertiaoside， dihydroquercetin and paeonol； in the fingerprints of powder decoction pieces， six chromatographic peaks were identified， namely， 5-hydroxyfurfural， monoglycoside， swertiamarin， dihydroquercetin， paeonol and benzoyl paeoniflorin. The results of content determination showed that in the first 5 minutes of the first decocting， the decocting rate of almost all the ingredients in the powder decoction pieces was faster than that of the traditional decoction pieces； after 40 min， the contents of other active ingredients were lower than those of traditional decoction pieces except for 5-hydroxyfurfural and paeonol. In the process of second decocting， except for paeonol and loganin， the contents of other ingredients in powder decoction pieces were higher than that in traditional decoction pieces； catechin was completely decocted from the traditional decoction pieces in the first decocting， while it could still be detected in the powder decoction pieces in the second decocting. There was little difference in the total decocted amount of the 8 ingredients in the two decoction pieces.CONCLUSIONSThe chemical composition of powder decoction pieces of Liuwei dihuang formula has no obvious advantages compared with traditional decoction pieces， and can not save the decocting time and the amount of medicinal materials.  
        关键词：powder decoction pieces;traditional decoction pieces;extraction process;fingerprint;content determination   
        7
        |
        0
        |
        0
        <HTML>
        <L-PDF><WORD><Meta-XML>
        <引用本文> <批量引用> 33161986 false
        发布时间：2023-02-22
      • GAO Weicheng,WANG Xiaoping,XIAO Xiaolin,SHI Yiwei,LIN Shaofen
        Vol. 34, Issue 1, Pages: 72-77(2023) DOI: 10.6039/j.issn.1001-0408.2023.01.14
        摘要：OBJECTIVETo comprehensively evaluate the quality of Eriobotrya japonica leaves from different producing areas.METHODSThe contents of alcohol-soluble extracts were determined by hot-dipping method using 30 batches of E. japonica leaves from different producing areas as samples. The contents of total flavonoids and total triterpene acids were determined by ultraviolet spectrophotometry. The contents of five kinds of triterpenic acids （euscaphic acid，crataegolic acid，corosolic acid，oleanolic acid and ursolic acid） were determined by HPLC. The quality of E. japonica leaves from different producing areas was comprehensively evaluated by using entropy weight technique for order preference by similarity to an ideal solution （TOPSIS）. The bivariate correlation analysis of E. japonica leaves was conducted by SPSS 22.0 software in terms of weight， comprehensive evaluation value， the content of alcohol-soluble extract， the contents of total flavonoids， total triterpene acids and five triterpenic acids.RESULTSThe contents of alcohol-soluble extract in 30 batches of E. japonica leaves were （24.56±0.08）%-（34.85±0.13）%； the contents of total flavonoids were （4.69±0.11）-（14.23±0.27） mg/g； the contents of total triterpene acid were （27.58±0.59）-（63.95±1.27） mg/g； the contents of euscaphic acid， crataegolic acid， corosolic acid， oleanolic acid and ursolic acid were （0.728±0.011）-（6.064±0.063）， （0.526±0.013）-（3.245±0.022）， （1.222±0.025）-（8.807±0.094）， （0.856±0.021）-（2.931±0.075）， （4.704±0.087）-（11.806±0.283） mg/g， respectively. The analysis result of entropy weight TOPSIS method showed that the top three samples with comprehensive evaluation values were S14 （Huotian Town， Yunxiao County， Zhangzhou， Fujian）， S19 （Qinnan District， Qinzhou， Guangxi） and S29 （Guoyang County， Bozhou， Anhui）. Comprehensive evaluation of E. japonica leaves was positively correlated with the contents of five kinds of triterpenic acids， such as euscaphic acid， crataegolic acid， corosolic acid， oleanolic acid and ursolic acid （P＜0.01）. The weight of E. japonica leaves was positively correlated with the comprehensive evaluation value （P＜0.01）.CONCLUSIONSThe qualities of E. japonica leaves from different producing areas are very different. Among them， the qualities of E. japonica leaves from Huotian Town， Yunxiao County， Zhangzhou of Fujian， Qinzhou Qinnan District of Guangxi， and Bozhou Guoyang County of Anhui are relatively better. The weight of E. japonica leaves is positively correlated with their quality.  
        关键词：triterpene acids;total flavonoids;entropy weight TOPSIS method;correlation analysis;producing areas   
        5
        |
        0
        |
        0
        <HTML>
        <L-PDF><WORD><Meta-XML>
        <引用本文> <批量引用> 33161910 false
        发布时间：2023-02-22
      • RAO Wenchen,SONG Xiaobing
        Vol. 34, Issue 1, Pages: 78-81(2023) DOI: 10.6039/j.issn.1001-0408.2023.01.15
        摘要：OBJECTIVETo evaluate the cost-utility of as-needed inhaled budesonide/formoterol versus budesonide maintenance therapy combined with as-needed inhaled terbutaline （hereinafter referred to as budesonide maintenance therapy） in patients with mild asthma from the perspective of the Chinese health service system.METHODSA Markov model of mild asthma was established based on an international multicenter randomized controlled clinical study （SYGMA 2 study）； the model cycle was one week， and the model had a whole horizon of 60 years. The cost only included direct medical cost， and utility value was derived from the data of EuroQol 5-Dimension 5-Level in the SYGMA 2 study and published literature. The total cost and total output of the above two inhalation therapies for patients with mild asthma were calculated， with discount rate of 5%. The stability of the model was evaluated by sensitivity analysis.RESULTSThe total cost of as-needed inhaled budesonide/formoterol and budesonide maintenance therapy were 25 884 yuan and 45 822 yuan， respectively， and the effectiveness were 30.51 quality-adjusted life years （QALYs） and 30.50 QALYs， respectively. The former scheme was an absolute advantage. One-way sensitivity analyses showed that the price of drug （terbutaline and budesonide/formoterol） and average number of inhalations per day were the main influencing parameters， but they had little influence on the results of basic analysis. Probabilistic sensitivity analysis showed that the probability of as-needed budesonide/formoterol being cost-effective was 100%.CONCLUSIONSCompared with budesonide maintenance therapy， as-needed inhalation of budesonide/formoterol in mild asthma patients is more cost-effective.  
        关键词：budesonide;formoterol;terbutaline;pharmacoeconomic evaluation;as-needed;maintenance therapy   
        17
        |
        7
        |
        0
        <HTML>
        <L-PDF><WORD><Meta-XML>
        <引用本文> <批量引用> 33162174 false
        发布时间：2023-02-22
      • LIU Kunshan,LI Mengdi,ZHAO Jianjun,CHENG Xinqi
        Vol. 34, Issue 1, Pages: 82-85(2023) DOI: 10.6039/j.issn.1001-0408.2023.01.16
        摘要：OBJECTIVETo investigate the effect of ropivacaine combined with dexmedetomidine on postoperative analgesia in women undergoing cesarean section， and to explore the feasibility of the opioid-free analgesia mode after cesarean section under spinal-epidural anesthesia.METHODSTotally 80 women undergoing cesarean section were randomly divided into observation group （ropivacaine combined with dexmedetomidine for analgesia） and control group （ropivacaine combined with opioid drug sufentanil for analgesia） ， with 40 cases in each group. The exercise and rest score in visual analogue scale （VAS） within 48 hours after operation， the use of analgesia pump （the time of first analgesia pump pressing， the times of analgesia pump pressing within 24 hours and 48 hours after operation）， the time of block （the onset time of spinal anesthesia sensory block， the time to the highest level of spinal anesthesia sensory block， the time of sensory recovery and the time of movement recovery） ， the time of prognosis （the time of gastrointestinal ventilation recovery， the time of getting out of bed and the hospitalization time）， and the incidence of adverse events were compared in 2 groups.RESULTSFinally， 64 parturients （32 in the observation group and 32 in the control group） were involved in the analysis. Compared with the control group， the recovery time of sensation and movement were significantly prolonged， the ventilation time was significantly shortened， and the incidence of nausea， vomiting and abdominal distension was significantly decreased in the observation group （P＜0.05） . There was no significant difference in the other indexes between the two groups （P＞0.05）.CONCLUSIONSRopivacaine combined with dexmedetomidine under spinal-epidural anesthesia could provide similar analgesic effect as combined with opioids drug sufentanil， shorten the time of gastrointestinal ventilation recovery， and reduce the incidence of nausea， vomiting and abdominal distension， with no increased risk of low blood pressure or urinary retention.  
        关键词：ropivacaine;dex- medetomidine;opioid-free analgesia;cesarean section   
        11
        |
        3
        |
        0
        <HTML>
        <L-PDF><WORD><Meta-XML>
        <引用本文> <批量引用> 33162283 false
        发布时间：2023-02-22
      • YIN Jinjin,DU Peili,TAN Xiangping,MEI Zhengrong,SHI Shengying,LIU Shaozhi
        Vol. 34, Issue 1, Pages: 86-90(2023) DOI: 10.6039/j.issn.1001-0408.2023.01.17
        摘要：OBJECTIVETo establish evaluation criteria for rational drug use of atosiban in clinic， and to provide reference for rational drug use of atosiban in clinic.METHODSBased on the drug instructions of atosiban acetate injection and related guidelines， the experts of the Evaluation Group of Rational Drug Use formulated the evaluation criteria of rational drug use， including 5 primary indexes and 8 secondary indexes. The weight coefficients of secondary indexes were calculated by analytic hierarchy process （AHP）， and the use of atosiban acetate injection in 190 pregnant women from the Third Affiliated Hospital of Guangzhou Medical University （referred to as “our hospital”） was evaluated retrospectively by technique for order preference by similarity to an ideal solution （TOPSIS）. The evaluation results were divided into three levels including reasonable， basic reasonable and unreasonable application based on the relative approach degree.RESULTSAmong 190 pregnant women， 49 （25.8%） were treated with atosiban reasonably， 39 （20.5%） were treated with atosiban basic reasonably， and 102 （53.7%） were treated with atosiban unreasonably. The evaluation results obtained by AHP-TOPSIS method were consistent with the actual situation in clinic. The main problems of the unreasonably use were super indications， unreasonable usage and dosage， over the course of treatment and the lack of proper economic consideration.CONCLUSIONSThe rationality evaluation criteria of atosiban’s clinical application are established by AHP-TOPSIS method； the evaluation results obtained by this method are quantifiable， scientific and reliable. The unreasonable use of atosiban is common in our hospital， and the management should be strengthened in clinical application.  
        关键词：rational drug use;evaluation criteria;analytic hierarchy process;technique for order preference by similarity to an ideal solution   
        14
        |
        3
        |
        0
        <HTML>
        <L-PDF><WORD><Meta-XML>
        <引用本文> <批量引用> 33161736 false
        发布时间：2023-02-22
      • LI Huiquan,LI Xiaojiang,ZHANG Xuejuan
        Vol. 34, Issue 1, Pages: 91-96(2023) DOI: 10.6039/j.issn.1001-0408.2023.01.18
        摘要：OBJECTIVETo re-evaluate systematic review/meta-analysis of escitalopram in the treatment of depression， and to provide reference for clinical use of escitalopram.METHODSRetrieved from CNKI， Wanfang database， VIP， SinoMed， PubMed and the Cochrane Library， etc.， systematic review/meta-analysis of escitalopram in the treatment of depression were collected from the construction of the database to May 17， 2022. The literatures were screened according to the inclusion and exclusion criteria， the basic information of the included literatures was extracted， and the methodological quality， reporting quality and evidence quality of the included literatures were evaluated by using AMSTAR 2 scale， PRISMA statement， and GRADE system， respectively.RESULTSA total of 16 systematic reviews/meta-analyses were included. The results of efficacy comparison showed that escitalopram in the treatment of depression was superior to sertraline in improving the total effective rate， and was comparable to paroxetine， duloxetine and fluoxetine in improving cure rate. The results of safety comparison showed that the safety of escitalopram was higher than that of paroxetine and venlafaxine. The overall methodological quality evaluation of AMSTAR 2 scale was low， and all of them were rated as extremely low； main reason was the lack of many key items. PRISMA score was between 12 and 23 points. Among them， there were 5 literatures with scores ＞21 points， and the reports were relatively complete， 10 literatures with scores between 15 and 21 points， and the reports had certain defects， and 1 literature with scores ≤15 points， with serious information missing. The results of the grading of GRADE evidence showed that， of the 160 included outcome indicators， 69 were moderate evidence， 64 were low-level evidence， and 27 were very low-level evidence.CONCLUSIONSThe total effective rate of escitalopram in improving depressive patients is not inferior to that of sertraline； compared with paroxetine， escitalopram is safer. However， the evidence level of the above conclusions is low.  
        关键词：depression;overview of systematic review;evidence-based medicine   
        13
        |
        3
        |
        0
        <HTML>
        <L-PDF><WORD><Meta-XML>
        <引用本文> <批量引用> 33161848 false
        发布时间：2023-02-22
      • ZHANG Bihua,SHAO Hui,YE Aijun,YANG Liping
        Vol. 34, Issue 1, Pages: 97-101(2023) DOI: 10.6039/j.issn.1001-0408.2023.01.19
        摘要：OBJECTIVETo evaluate the efficacy， safety and economical efficiency of Xuesaitong injection in the treatment of stroke by rapid health technology assessment，so as to provide evidence for clinical rational drug use.METHODSRetrieved from Wanfang database， CBM， CNKI，PubMed，Cochrane Library，Embase， INAHTA and HTAI databases or organization websites， health technology assessment （HTA） reports， meta-analysis/systematic reviews and pharmacoeconomic studies related to Xuesaitong injection in the treatment of stroke were summarized and analyzed.RESULTSA total of 29 pieces of literature were included. Among them， 14 studies were conducted on meta-analysis/systematic reviews，15 studies were conducted on pharmacoeconomics， HTA was not obtained. The results of meta-analysis/systematic reviews showed that Xuesaitong injection had certain advantages for stroke in improving the total effective rate， clinical symptoms and related scale scores compared with blank control group and some drug control groups. Safety studies had shown that the adverse reactions of Xuesaitong injection were mainly allergic-like reactions. The results of pharmacoeconomic evaluation are quite different， which may also be related to the long time span among various studies and the adjustment of some drug prices.CONCLUSIONSXuesaitong injection in the treatment of stroke is helpful to improve the clinical efficacy and evaluation indexes， but there are some serious adverse reactions， and it is not economically superior to some chemical drugs.  
        关键词：stroke;pharmacoeconomics;rapid health technology assessment   
        7
        |
        5
        |
        0
        <HTML>
        <L-PDF><WORD><Meta-XML>
        <引用本文> <批量引用> 33161813 false
        发布时间：2023-02-22
      • LI Jie,CHEN Xiaofei,XU Zihan,LIU Xiaoyan,ZHANG Yuechan,HAN Yi,ZHANG Wei,JIANG Zhitao
        Vol. 34, Issue 1, Pages: 102-106(2023) DOI: 10.6039/j.issn.1001-0408.2023.01.20
        摘要：OBJECTIVETo systematically evaluate the efficacy and safety of glucokinase activators in the treatment of type 2 diabetes mellitus.METHODSPubMed， Cochrane Library， Web of Science， Embase and CNKI databases were searched from the inception to March 2022. Randomized controlled trials about glucokinase activators versus placebo （or other oral hypoglycemic agents） in the treatment of type 2 diabetes were included， data were extracted and meta-analysis was analyzed using RevMan 5.4 software.RESULTSA total of 9 studies with 215 0 patients were included. In terms of hypoglycemic effect， compared with control group， glucokinase activators significantly reduced glycosylated hemoglobin （HbA1c） [MD＝－0.40， 95%CI（－0.53， －0.26）， P＜0.000 01]， fasting blood glucose[MD＝－0.53， 95%CI（－0.85， －0.20）， P＝0.001] and 2 h postprandial blood glucose [MD＝－2.28， 95%CI（－2.68， －1.88）， P＜0.000 01] in diabetic patients. In terms of safety， the incidence of hypoglycemia caused by glucokinase activators was higher than control group on the whole [RR＝1.55， 95%CI（1.20，2.01）， P＝0.000 8]. According to the subgroup analysis of organs activated by glucokinase activator， the incidence of hypoglycemia in the pancreas-liver dual activator group [RR＝1.44， 95%CI（1.11，1.89）， P＝0.007] and liver-selective activator group [RR＝2.26， 95%CI（1.02，5.03）， P＝0.05] was higher than that in the control group， the difference was statistically significant.CONCLUSIONSGlucokinase activators can effectively reduce HbA1c， fasting blood glucose and 2 h postprandial blood glucose in patients with type 2 diabetes， but the risk of hypoglycemia remains to be addressed.  
        关键词：type 2 diabetes mellitus;meta-analysis;efficacy;safety   
        11
        |
        5
        |
        0
        <HTML>
        <L-PDF><WORD><Meta-XML>
        <引用本文> <批量引用> 33161911 false
        发布时间：2023-02-22
      • DONG Shujie,ZHENG Siqian,XU Xiaohan,SHI Weilong,LI Huibo,ZHAO Rongsheng,YANG Li
        Vol. 34, Issue 1, Pages: 107-110(2023) DOI: 10.6039/j.issn.1001-0408.2023.01.21
        摘要：OBJECTIVETo build a standardized simulation teaching system for resident pharmacists and evaluate its effects， and to provide reference for improving the competency of resident pharmacists. METHODSThe established simulation teaching system for pharmacy residents’ standardized training in the study included revising the simulation teaching syllabus， setting up simulation teaching courses， implementing the teaching method through “six types of simulations”， applying objective structured clinical examination （OSCE） for assessment， building a simulation teaching team and strengthening the simulation teaching management. The effect evaluation was perfermed with mixed research method， and qualitative and quantitative research methods were used to collect and analyze data and information.RESULTS & CONCLUSIONSCompared with the traditional teaching system， the passing rate of graduation examination （71.4% vs. 100%） and the score of after-department examination [（76.2±7.8） vs. （90.4±4.9）] under the simulation teaching mode were higher； through questionnaire surveys and qualitative interviews， we found that resident pharmacists who went through simulation teaching gave positive feedback on the role and impact of this system. The simulation teaching system can be used with good generalizability for the standardized training of resident pharmacists， and can provide strong basis and support for the high-quality development of hospital pharmacy.  
        关键词：competency;simulation teaching;mixed research methods   
        16
        |
        9
        |
        0
        <HTML>
        <L-PDF><WORD><Meta-XML>
        <引用本文> <批量引用> 33161885 false
        发布时间：2023-02-22
      • LIU Guangyu,WANG Qi,SU Ling
        Vol. 34, Issue 1, Pages: 111-116(2023) DOI: 10.6039/j.issn.1001-0408.2023.01.22
        摘要：Polysaccharide is a recognized immunomodulator that has been shown to have inhibitory effects on a variety of cancer cells and has the potential to be developed as an anti-cancer drug. Pancreatic cancer， one of the cancers with the highest mortality rate， is treated with long-term chemotherapeutic drugs and is prone to a variety of side effects such as immune deficiency， fatigue， and neurological lesions. The polysaccharide anti-pancreatic cancer research landscape both domestically and internationally is summarized in this publication. By regulating nuclear factor-κB， Hippo-Yes-associated protein， integrin and other signaling pathways， polysaccharide components play an anti-pancreatic cancer role by multi-target ways， such as inducing apoptosis and autophagy， inhibiting proliferation， migration and invasion of cancer cells， and regulating the cancer cell cycle.  
        关键词：pancreatic cancer;effect mechanism   
        12
        |
        1
        |
        0
        <HTML>
        <L-PDF><WORD><Meta-XML>
        <引用本文> <批量引用> 33162259 false
        发布时间：2023-02-22
      • ZHAN Shipeng,MA Pan,LIU Fang
        Vol. 34, Issue 1, Pages: 117-121(2023) DOI: 10.6039/j.issn.1001-0408.2023.01.23
        摘要：Machine learning has been applied in the medical field due to its powerful data analysis and exploration capabilities. In recent years， more and more studies have applied it to therapeutic drug monitoring and individual drug therapy of immunosuppressants， anti-infective drugs， antiepileptic drugs， etc. Compared with the traditional population pharmacokinetic modeling methods， the constructed models based on machine learning can predict blood drug concentration and drug dose more accurately， improve the level of clinical precision drug use and reduce the occurrence of adverse drug reactions. Based on this， this article reviews the application of machine learning in therapeutic drug monitoring and individual drug therapy， with a view to providing theoretical basis and technical support for clinical precise drug use.  
        关键词：therapeutic drug monitoring;immunosuppressants;anti-infective drugs;individual drug therapy   
        17
        |
        9
        |
        0
        <HTML>
        <L-PDF><WORD><Meta-XML>
        <引用本文> <批量引用> 33161928 false
        发布时间：2023-02-22
      • LI Guoqing,JIAO Ping,WANG Ruifang,ZHANG Dujuan
        Vol. 34, Issue 1, Pages: 122-128(2023) DOI: 10.6039/j.issn.1001-0408.2023.01.24
        摘要：Breast cancer is a malignant tumor that seriously threatens women’s health at present. Although surgical treatment is the most direct and effective， it is limited by many factors and needs to be assisted by other treatments. In addition to conventional radiotherapy， these adjuvant therapies also include chemotherapy， gene therapy， phototherapy and so on. However， the therapeutic agents used in these treatment methods have some limitations， such as poor water-solubility， instability and targeting. With the development of nano-technology， more and more researchers construct and study nano delivery system for breast tumor treatment， such as response system designed based on tumor microenvironment， temperature sensitive response system， nano delivery system based on specific proteins of tumor cell membrane， etc. The author summarizes the nano delivery system， and finds that these nano delivery systems can not only improve the water-solubility and stability of the therapeutic agents， but also accurately deliver them to the breast tumor site by targeted means， improve the efficacy and reduce toxic side effects， which provides new ideas for the treatment of breast cancer in the future.  
        关键词：breast cancer;chemotherapy;gene therapy;phototherapy   
        14
        |
        1
        |
        0
        <HTML>
        <L-PDF><WORD><Meta-XML>
        <引用本文> <批量引用> 33162002 false
        发布时间：2023-02-22
      0