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Association between hepatic sinusoidal obstruction syndrome induced by monocrotaline and neutrophil extracellular traps LI Yue, ZHANG Shuang, SUN Xin, LIU Chenghai, QIU Furong 2023, 20(2): 121-126.  DOI: 10.19803/j.1672-8629.20220667 Abstract ( 144 )   PDF (1932KB) ( 132 )   Objective To investigate the association between neutrophil extracellular traps (NET) and hepatic sinusoidal obstruction syndrome (HSOS) induced by monocrotaline (MCT). Methods Ten Sprague-Dawley(SD) rats were randomly divided into the normal group and HSOS model group based on body weight, with five in each. The normal group was gavaged with saline while the model group received a single gavage of MCT (90 mg·kg-1). Forty-eight hours after MCT administration, blood and liver samples were collected. The effects of MCT on histological changes of the liver, alanine aminotransferase and alkaline phosphatase levels, hepatic myeloperoxidase activity, protein expression of citrullinated histone H3 (Cit H3), immunofluorescence staining of NET structure as well as expressions of NET associated genes were investigated. Results In the model group, macroscopic and histological findings revealed liver congestion, sinusoidal alteration, perisinusoidal infiltration of red cells and inflammatory cells, and multifocal hepatocellular necrosis. Furthermore, plasma ALT and ALP levels were significantly increased compared with the normal group(P<0.01). Administration of MCT to rats resulted in a significant elevation of hepatic MPO activity and Cit H3 expression. It NET formation was also observed in the liver lobes in MCT-treated rats. Additionally, the mRNA levels of C-X-C motif chemokine receptor 2(CXCR2), and toll-like receptor 4 (TLR4) were significantly increased in the MCT group (P<0.01). Conclusion NET may be involved in the mechanism responsible for MCT-induced HSOS. References | Related Articles | Metrics

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Clinic diagnosis and treatment of herb-induced liver injury LI Meng, LI Rongrong, LIU Chenghai 2023, 20(2): 127-131.  DOI: 10.19803/j.1672-8629.20220661 Abstract ( 272 )   PDF (1297KB) ( 282 )   Objective To introduce the clinical features of herb-induced liver injury (HILI) for better prediction and prevention of HILI. Methods The clinical epidemiology, risk signals and clinical diagnosis, risk factors and pathogenesis, management, treatment and medication of HILI were reviewed based on the latest research at home and abroad. Results and Conclusion The clinical manifestations of HILI are diverse and the toxic mechanism is complex, which is more prominent in drug induced liver injury, so, brings great challenges to the clinical prevention and treatment of HILI. Clinical awareness of drug safety and attention to the detection and screening of HILI cases should be continuously raised. Long-term follow-up cohorts should be established and integrated with clinical, pharmacological and clinical epidemiological disciplines to improve the clinical prevention and treatment of HILI and promote the level of clinical safety in the use of Chinese medicine. References | Related Articles | Metrics

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Humoral immune characteristics of peripheral blood of CAP patients with antibiotic-associated DILI WANG Yu, HUANG Jingyi, HOU Lixin, LI Shuang, CUI Yongkang, HUANG Lanwei 2023, 20(2): 132-135.  DOI: 10.19803/j.1672-8629.20220660 Abstract ( 124 )   PDF (1451KB) ( 129 )   Objective To explore the correlations between humoral immune indexes of peripheral blood of patients with community acquired pneumonia (CAP) and drug-induced liver injury (DILI) associated with antibiotics during treatment. Methods A total of 1 356 patients with CAP who were treated with antibiotics between June 1, 2021 and June 30, 2022 in Shanghai Baoshan District Hospital of Integrated Traditional Chinese and Western Medicine were retrospectively selected. Patients with DILI were selected as the case group, while those without DILI were matched as the control group at the ratio of 1∶2. The clinical data of the patients were collected, the differences between the two groups were analyzed, and multivariate logistic regression was used to analyze the influencing factors of DILI in CAP patients receiving antibiotics. Results The total number of CAP patients receiving antibiotics during the retrospective study was 1 356, 34 of whom developed antibiotic-related DILI, so the incidence of DILI was 2.5%. The data on 31 cases of antibiotic-related DILI and 63 cases of the control group were successfully matched. The antibiotic-related DILI was of the hepatocyte injury type. The clinical data of the case group and the control group were balanced and comparable in terms of gender, age (±5 years), main diagnosis, severity of diseases (CURB-65 score), underlying diseases, treatment courses and doses, and diet and nursing were consistent. There was no significant difference in the types of antibiotics used (penicillin, cephalosporins, carbapenems, quinolones, aminoglycosides and macrolides) between the two groups. The humoral immune indexes of peripheral blood, gender, age, CURB-65 score, and antibiotics were included in binary regression analysis, and the results showed that IgG and total IgE were the risk factors for antibiotic-related DILI and were of statistical significance (P=0.028, P=0.038). The AUCs of ROC curves based on risk factors were 0.461 (95%CI: 0.336~0.587) and 0.683 (95%CI: 0.560-0.806), respectively, indicating that total IgE had a feasible discrimination for the diagnosis of antibiotic-related DILI. Conclusion Humoral immune factors, especially abnormal elevation of total IgE, can significantly increase the odds of antibiotic-related DILI in CAP patients, indicating that adaptive humoral immunity may be involved in the pathogenesis of antibiotic-related DILI. References | Related Articles | Metrics

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A case of suspected drug induced liver injury caused by Senecio Scandens YU Jie, ZHU Haoxiang, ZHANG Jiming 2023, 20(2): 136-139.  DOI: 10.19803/j.1672-8629.20220668 Abstract ( 152 )   PDF (1249KB) ( 158 )   Objective To analyze the relationship between Senecio scandens and drug induced liver injury, so as to provide reference for clinical safe drug use. Methods A case of hepatic sinusoidal obstruction syndrome after taking suspected senecio herb was reported. The chromatograms of the standard senecilline, which is one kind of Pyrrolizidine Alkaloids, with the patient’s blood and urine samples were compared, and the correlation between the suspected drug and liver injury was assessed according to the Roussel Uclaf Causality Assessment Method(RUCAM) and guidelines for clinical diagnosis and treatment of herb-induced liver injury. Results The patient’s liver injury was manifested as hepatic sinusoidal obstruction syndrome. The patient’s urine sample propably contained the analogues or metabolites of senecilline. The RUCAM scale score was eight points, judging that there was a correlation between suspected herbal medicine and liver injury. Conclusion When taking traditional Chinese medicine, carefully evaluate whether there are Senecio scandens. If liver injury occurs, the drug should be discontinued promptly and targeted investigations and treatment should be carried out. References | Related Articles | Metrics

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Succession medicinal substances of calculus bovis with infrared spectroscopy coupled with machine learning methods SHI Yan, WANG Xiaowei, WEI Feng, MA Shuangcheng 2023, 20(2): 140-145.  DOI: 10.19803/j.1672-8629.20210405 Abstract ( 98 )   PDF (2209KB) ( 86 )   Objective To explore a method based on machine learning for distinguishing succession medicinal substances of calculus bovis with infrared spectroscopy. Methods After being preprocessed using an autoscale method, data on infrared spectra was analyzed with unsupervised analysis methods and supervised ones respectively. With the help of a genetic algorithm, the most suitable model type and related parameters were studied. The most suitable model type was the XY-Fused network with 25(5×5) as the number of neurons and 1000 set as the epoch. The model with boundaries was trained with the batch pattern. Nine samples were selected randomly among the 43 samples as the test set. The rest were used as the calibration set. Results Accuracies of cross validation were 94.1%, 94.1%, 94.1%, respectively, and the average was 94.1%. Prediction accuracies for the test set were 100%, 83.3%, 100%, respectively, and the average was 94.4%. Conclusion The model established here can be used for distinguishing succession medicinal substances of cow-bezoar with infrared spectroscopy, and is of referential value for studies on succession medicinal substances of calculus bovis. References | Related Articles | Metrics

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UPLC fingerprints of tripterygium glycosides tablets from different manufacturers WANG Yadan, YAN Jiangong, CHEN Minghui, PANG Yu, DAI Zhong, MA Shuangcheng 2023, 20(2): 146-151.  DOI: 10.19803/j.1672-8629.20210474 Abstract ( 86 )   PDF (1582KB) ( 88 )   Objective To establish UPLC fingerprints of tripterygium glycoside tablets, and to evaluate the quality of preparations from different manufacturers by chemometrics. Methods Chromatographic separation was performed on the Waters Cortecs T3 column (2.1 mm × 100 mm, 1.6 μm). Acetonitrile-water was adopted as the mobile phase for gradient elution. The flow rate was 0.4 mL/min and the detection wavelength 220 nm. ChemPattern software was used for the establishment of the common pattern of fingerprints, similarity evaluation, and for principal component analysis and cluster analysis. At the same time, the common peaks were identified using the UPLC-QTOF-MS method. Results The UPLC fingerprints of 25 batches of tripterygium glycoside tablets from 9 manufacturers were established, and 51 common peaks were determined. Among them, 23 were identified, and most of them were found to be alkaloids. The similarity of the tested samples ranged from 0.18 to 0.99, suggesting that the quality of the samples from different manufacturers and even that of samples of different batches from the same manufacturer varied greatly. Principal component analysis and cluster analysis divided the nine manufacturers’ preparations into three categories and screened out three main different components. Conclusion UPLC fingerprints can reflect the variations in tripterygium glycoside tablets from various manufacturers, which can provide reference for quality evaluation of the preparations based on chemometrics. References | Related Articles | Metrics

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Interactions of Psoralea corylifolia L. with Astragali Radix and Paeoniae Radix Rubra in rats based on pharmacokinetics ZHAI Yuxia, ZHANG Xiaoying, MEN Weijie, CHENG Liyuan, ZHANG Yue, ZHOU Kun 2023, 20(2): 152-156.  DOI: 10.19803/j.1672-8629.20211083 Abstract ( 126 )   PDF (1744KB) ( 79 )   Objective To study the changes of plasma pharmacokinetic parameters of psoralen and isopsoralen, the main toxic components of psoralen, after the compatibility of Astragali Radix, Paeoniae Radix Rubra and Psoralea corylifolia L.. Methods Thirty-two male SD rats were randomly divided into four groups: Psoralea corylifolia L. group, Psoralea corylifolia L.-Astragali Radix group, Psoralea corylifolia L.- Paeoniae Radix Rubra group, Psoralea corylifolia L.-Astragali Radix- Paeoniae Radix Rubra group. Blood was collected from the inner canthus at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, and 24 h after single intragastric administration. Plasma concentrations of psoralen and isopsoralen were detected with the UPLC -MS/MS method, and pharmacokinetic parameters were calculated via a non-attoventricular model using DAS3.0 software. Results The cmax and AUC of psoralen and isopsoralen decreased significantly when Psoralea corylifolia L. was combined with Paeoniae Radix Rubra, so did the cmax of isopsoralen in rat plasma when Psoralea corylifolia L. was combined with Astragali Radix. However, after the combination of Psoralea corylifolia L. and Astragali Radix and Paeoniae Radix Rubra, the AUC0-t of psoralen and isopsoralen decreased significantly in rat plasma, so did the AUC0-∞ and cmax of isopsoralen. Conclusion The combination of Astragali Radix, Paeoniae Radix Rubra and Psoralea Corylifolia L. can reduce the exposure of psoralen and isopsoralen in vivo. Paeoniae Radix Rubra or Astragali Radix plus Psoralea corylifolia L. can reduce plasma cmax and AUC0-t , but the MRT of isopsoralen in plasma of rats in the Psoralea corylifolia L.- Astragali Radix- Paeoniae Radix Rubra group is prolonged, the specific mechanism of which needs to be further studied. References | Related Articles | Metrics

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Genotoxicity of 5-hydroxymethylfurfural and its dipolymer and metabolite LIN Ni, YE Qian, GENG Xingchao, WANG Xue, JIN Hongtao, WEN Hairuo 2023, 20(2): 157-162.  DOI: 10.19803/j.1672-8629.20210706 Abstract ( 151 )   PDF (1473KB) ( 93 )   Objective To evaluate the potential genotoxicity of impurities-5-hydroxymethylfurfural (5-HMF), its polymer 5,5’-oxydimethylenebis(2-furfural) (OMBF), and its metabolite 5-sulfooxymethylfurfural (5-SMF). Methods The genotoxicity of 5-HMF, OMBF and 5-SMF was predicted by means of Derek and Sarah with the quantitative structure-activity relationship (QSAR) technology. The bacterial reverse-mutation (Ames) test and single cell gel electrophoresis assay (SCGE, also called the comet assay) were performed to verify the above results. In Ames tests, the potential mutagenicity was evaluated using six strains of S. typhimurium (TA97、TA98、TA100、TA102、TA1535 and TA1537) treated with five different concentrations of 5-HMF, OMBF and 5-SMF with or without S9 mix from liver microsomes of mice, rats or humans and incubated for 48 h. DMSO 20 μg/well served as the vehicle control. In the absence of S9 mix, AF-2, NaN3 and 9-AA served as the positive control, otherwise 2-AA served as the positive control. When TA1535 and TA1537 had three times as many colonies as the vehicle control and when the number of colonies of TA97, TA98, TA100 and TA102 was twice that of the vehicle control, the test compound was considered mutagenic. Results In silico evaluation by Derek software showed that 5-HMF and 5-SMF were equivocally positive mutagenic and OMBF was inactive, while Sarah software predicted that 5-HMF and 5-SMF were positive mutagenic and OMBF was equivocally positive mutagenic. Ames test results demonstrated that 5-HMF and OMBF at a dose greater than 750 μg/well increased the number of TA100 revertant colonies only with rat-liver S9 mix. 5-SMF was positive mutagenic with mouse-, rat- or human-liver S9 mix on TA97, TA100, TA102 and TA1535 at a dose above 20~40 μg·well-1, or without S9 mix on TA97, TA98, TA100 and TA102 at a dose over 50 μg·well-1. Conclusion 5-HMF and OMBF show potential mutagenicity with a rat-liver S9 mix, while 5-SMF shows mutagenicity with/without S9 mix in vitro. Therefore, 5-HMF, OMBF and 5-SMF are class 2 genotoxic impurities, thus the limit of the three impurities should be enforced to ensure the safety of drugs, especially for people who may be chronically exposed to any of them. References | Related Articles | Metrics

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Study on the incompatibility of Veratrum nigrum Linn. and Sophora flavescens Ait. based on UPLC-QTOF/MS WANG Chao, WANG Yuguang, MA Zengchun, GAO Yue 2023, 20(2): 163-167.  DOI: 10.19803/j.1672-8629.20220590 Abstract ( 67 )   PDF (2009KB) ( 60 )   Objective To investigate the changes of toxic compounds in the co-decoction of Sophora flavescens Ait. and Veratrum nigrum Linn. in order to provide data for studies on their incompatibility. Methods UPLC-QTOF/MS was used to detect the co-decoction and single decoction related to the incompatibility Sophora flavescens Ait. and Veratrum nigrum Linn.. The differences in characteristic compounds between the two groups were analyzed via principal component analysis (PCA), orthogonal partial least squares discriminant (OPLS-DA) and variable importance projection (VIP). The potential characteristic compounds were quickly identified by means of mass spectrometry database search. Results The contents of veratrum steroid alkaloids (VSA) derived from Veratrum nigrum Linn. increased significantly in the co-decoction of Sophora flavescens Ait. and Veratrum nigrum Linn.. A comparison between the two groups showed that there were significant differences in eight chemical components. The contents of veratrosine (peak 3), veralomine (peak 7), pseudojervine (peak 2), veratramine (peak 6), yibeissine (peak 4), 3-veratroyl- zygadenine (peak 9), verazine (peak 11) increased significantly, all of which might be potential chemical markers of toxicity and side effects caused by their compatibility. Conclusion The co-decoction of Sophora flavescens Ait. and Veratrum nigrum Linn. can promote the dissolution of VSA. The incompatibility of Sophora flavescens Ait. and Veratrum nigrum Linn. may be closely related to the content increase of several toxic components. The 10∶1 ratio of the co-decoction can be considered to underlie the contraindication of the incompatibility of Sophora flavescens Ait and Veratrum nigrum Linn.. References | Related Articles | Metrics

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Determination of contents of NDMA in ranitidine hydrochloride substances and products by LC-HRMS LIU Bo, CHEN Xintong, ZHANG Qingsheng, FAN Huihong 2023, 20(2): 168-170.  DOI: 10.19803/j.1672-8629.20210659 Abstract ( 76 )   PDF (1515KB) ( 83 )   Objective To establish an LC-HRMS method for the determination of NDMA genotoxic impurities of analogs of ranitidine substances and products. Methods The separation was carried out on a C18 column (100 mm×4.6 mm, 3 μm) by liner gradient elution using 0.1% formic acid as mobile phase A and 0.1% formic acid acetonitrile as mobile phase B. The HRMS determination of NDMA was conducted by means of positive electrospray ionization parallel reaction monitoring using the internal reference method. Results Linear calibrations were established for NDMA in the range of 0.5 to 100 ng·mL-1. The limits of detection and quantification proved to be as low as 0.3 and 0.5 ng·mL-1 respectively. The average recoveries were between 82.9% and 119.2%. The content of NDMA in the 10 samples detected with this method ranged from 0.000 002% to 0.000 014%. Conclusion The established LC-HRMS method has been validated to be suitable for the simultaneous quantitative determination of NDMA genotoxic impurities in ranitidine. References | Related Articles | Metrics

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Mechanisms of Laportea bulbifera against rheumatoid arthritis FU Changli, LU Yuan, CHEN Siying, WANG Yonglin, LI Yongjun, WANG Aimin, LIU Chunhua 2023, 20(2): 171-176.  DOI: 10.19803/j.1672-8629.20210654 Abstract ( 52 )   PDF (3438KB) ( 61 )   Objective To study the mechanism of the components of Laportea bulbifera absorbed in blood in the treatment of rheumatoid arthritis (RA) based on network pharmacology and molecular docking. Methods The protein targets of the components and disease-related protein targets were predicted in the database. The protein-protein interactions of the common protein targets were analyzed via the String database. The Metascape database was used to carry out Gene Ontology (GO) and pathways analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG). Network diagrams of “absorbed components - targets” and “components - targets - signal pathways” were constructed to obtain the key targets. Molecular docking between the components absorbed in blood and potential key targets were analyzed using AutoDock vina software to screen and verify the main active components and targets of Laportea bulbifera in the treatment of RA. Results The results showed that there were 22 components or metabolites in blood from Laportea bulbifera, which acted on 292 targets linked to RA. The core targets might be INS, IL-6, MAPK3 and TNF. The predicted target genes of Laportea bulbifera on RA mainly involved the response to cellular nitrogen compounds, hormone stimulation and organic nitrogen compound reaction. These components in blood from Laportea bulbifera might mainly act on TNF signaling pathway and Th17 cell differentiation signaling pathways. Molecular docking results showed that flavonoids and phenolic acids were the main components that could interact strongly with the core targets, and that they could have strong affinity with multiple targets. Conclusion The mechanism of Laportea bulbifera against RA is possibly associated with multi-ingredients, multi-targets and multi-pathways. The main active components (flavonoids and phenolic acids) act on key proteins including MAPK3, PTGS2, TNF and IL-6 and regulate Th17 cell differentiation and TNF signaling pathways. References | Related Articles | Metrics

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Mechanisms of genipin-induced hepatotoxicity by using network pharmacology and transcriptomics WANG Xiaohui, ZHANG Fan, XIA Wenbin, WEI Yuhui 2023, 20(2): 177-180.  DOI: 10.19803/j.1672-8629.20210700 Abstract ( 110 )   PDF (1657KB) ( 101 )   Objective To explore the mechanism of genipin-induced hepatotoxicity by network pharmacology and transcriptomics. Methods Network pharmacology: Potential targets of genipin were screened by searching TCMSP, Pharmapper, Stitch and CTD databases. Meanwhile, disease-related targets were retrieved from Disgenet, CTD, PharmGKB, GeneCards and NCBI Gene databases using “Chemical and drug-induced liver injury” as the keywords. STRING was used for target interaction analysis, while Cytoscape software was used to construct a genipin-hepatotoxic target-disease network model. Finally, DAVID was used to perform GO enrichment and KEGG pathway analysis of targets of genipin-induced hepatotoxicity. Transcriptomics: Human HepaRG cells were subjected to interventions by blank and genipin medium respectively for 24 h. The Illumina high-throughput sequencing platform was used for transcriptome sequencing and bioinformatics analysis. Results Network pharmacological screening showed that genipin could act on 142 targets, 112 of which were related to hepatotoxicity. According to the protein-protein interaction (PPI) network map, there were 92 nodes and 382 edges. Enriched analysis showed that the targets of genipin-induced hepatotoxicity were mainly concentrated in PI3K/Akt signaling pathway, TNF signaling pathway, FOXO signaling pathway and NF-κB signaling pathway. Differential genes of the genipin group and control group were compared with those of the gene database, and a false discovery rate (FDR) <0.01 and Fc (fold change) ≥4 were selected as screening conditions. A total of 1 160 differential gene were found. KEGG enrichment analysis showed that the differential genes were mainly involved in TNF signaling pathway, transcription disorders, and ribosome metabolism. TNF signaling pathway played a key role in genipin-induced hepatotoxicity as was evidenced by network pharmacological results. Conclusion Genipin-induced hepatotoxicity may be related to the TNF signaling pathway, which induces inflammation, oxidative stress and cell apoptosis. References | Related Articles | Metrics

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Identification of chemical constituents in Jiawei Xiaoyao pills by UPLC-Q-TOF-MSE combined with UNIFI informatics platform SUN Jian, LIU Ziwei, LIU Ying, ZHANG Meiyu, LI Mengying, ZHANG Haiming, NIE Yinglan, QUAN Jianye, YAN Han, PENG Juan, LI Yucheng, YANG Shubin 2023, 20(2): 181-190.  DOI: 10.19803/j.1672-8629.20211148 Abstract ( 61 )   PDF (2145KB) ( 76 )   Objective To analyze and identify the chemical constituents of Jiawei Xiaoyao pills with high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MSE) so as to provide data for quality control of the compound. Methods The ACQUITY UPLC BEH C18 column (2.1×100 mm, 1.7 μm, Waters) was used with 0.1% formic acid water-acetonitrile as the mobile phase. The injection volume was 5 μL, the flow rate 0.3 mL·min-1, and the column temperature 40℃. Electrospray ionization (ESI) ion source was used for compound mass spectrometry detection and analysis in positive and negative modes. Structural confirmation was accomplished based on data on mass spectrometry collected from the UNIFI platform in the MSE mode in combination with compound excimer ions, mass spectrum cleavage pathway and reference substance. Results A total of 78 chemical components were identified by analyzing the molecular ion peaks and secondary mass spectrometry characteristic fragment ions of the target compound, and according to the cracking of reference substances and related literature. There were 3 sesquiterpenoids, 4 phenylpropanoids, 13 monoterpenoids, 7 phenols, 5 iridoids, 10 flavonoids, 23 triterpenoids and 13 other compounds. Conclusion UPLC-Q-TOF-MSE technology can be used to quickly analyze and identify the main compound types of compound Jiawei Xiaoyao pills, which can provide data for quality control of the compound and for subsequent studies on the substance basis of pharmacodynamics. References | Related Articles | Metrics

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Effects of elemene emulsion injection on liver function injury in the real world based on propensity scores DU Ying, ZHAO Xiaoxiao, XIE Yanming, YU Xiaokang 2023, 20(2): 191-195.  DOI: 10.19803/j.1672-8629.20211116 Abstract ( 64 )   PDF (1356KB) ( 89 )   Objective To explore the causes of liver function injury associated with elemene emulsion injection in the real world. Methods The clinical data on 4 421 patients who had used elemene emulsion injection at least once in 21 big hospitals nationwide between January 1, 2003 and July 31, 2019 were collected from the integrated data warehouse of the large hospital information system (HIS) established by the Institute of Clinical Basic Medicine of Chinese Medicine of the Chinese Academy of Traditional Chinese Medicine. Twenty-seven patients with abnormal liver function were included. Through SOMTE sampling, 27 patients with liver function impairment and 108 patients in the control group were finally obtained. All the factors that affected normal liver function in the 135 cases were processed by Logistic regression, weighted Logistic regression of gradient elevator tendency scores without covariates and weighted Logistic regression of gradient elevator tendency scores with covariates. Results Logistic regression showed that there were 4 factors (P<0.05), namely, multiple secondary malignant tumors, combination with furosemide 7 days before administration, combined use with lidocaine (sirocarine), and vitamins. Further analysis using the tendency score method showed that multiple secondary malignant tumors had an impact on liver function. The use of furosemide 7 days before elemene emulsion injection might affect liver function. Whether lidocaine combined with elemene emulsion injection would lead to liver function injury needs to be studied, and vitamins combined with elemene emulsion injection would not affect liver function. Conclusion There is no compelling evidence that the use of elemene emulsion injection will lead to liver function injury. For more evidence, rigorous randomized controlled experiments are required. References | Related Articles | Metrics

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Visual analysis of ADR induced by Chinese medicine based on CiteSpace knowledge maps DING Xueli, HUANG Zhengkai, AN Xiaoye, YANG Xiaoxiong, ZHANG Bing, LIN Zhijian 2023, 20(2): 196-200.  DOI: 10.19803/j.1672-8629.20211219 Abstract ( 98 )   PDF (1677KB) ( 131 )   Objective To keep track of the current research and developments related to adverse cardiac reactions caused by traditional Chinese medicine through visual analysis. Methods Literature that was published between January 1, 1980 and January 31, 2022 and concerned with adverse cardiac reactions caused by traditional Chinese medicines was retrieved from CNKI, Wanfang and VIP databases respectively. CiteSpace5.8.R2 software was used to analyze the years of publication, journals, authors, institutions and key words. Results The number of articles published in the field of cardiotoxicity caused by traditional Chinese medicines gradually increased. Six stable core research teams were formed in this field, but there was little collaboration between them. The number of publications by Feng Qun and Guan Yuechen respectively was the largest, which played an important role in promoting the development of this field. Research focused on the mechanism prediction of ADR induced by TCM, the toxicity reduction of TCM processing and compatibility, and the evaluation indexes of cardiotoxicity (electrocardiograms, cardiomyocytes and ion channels). Conclusion There has been more research on adverse cardiac reactions caused by traditional Chinese medicines, especially on the cardiotoxicity of toxic traditional Chinese medicines and the combination of traditional Chinese medicines. Emergent analysis suggests that more effort will be made to study the evaluation indexes of cardiotoxicity of TCM, establish the evaluation system of TCM research and development, elucidate the molecular mechanism of TCM compatibility and toxicity reduction based on zebrafish models, and find out how various markers play a synergistic or antagonistic role. References | Related Articles | Metrics

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Automatic monitoring and risk factors of acute kidney injury in 116097 dosing cases of flurbiprofen axetil WANG Jiaxi, GUO Daihong, ZHANG Bo, Li Boyan, GUO Haili 2023, 20(2): 201-205.  DOI: 10.19803/j.1672-8629.20210741 Abstract ( 126 )   PDF (1485KB) ( 128 )   Objective To find out about the incidence, clinical characteristics and risk factors of flurbiprofen axetil-related acute kidney injury among inpatients. Methods Based on the Adverse Drug Events Active Surveillance and Assessment System (ADE-ASAS) in medical institutions, all the hospitalized patients using flurbiprofen axetil in Chinese PLA General Hospital between December 1, 2010 and November 30, 2020 were retrospectively monitored and a case-control study was conducted to analyze the incidence, clinical characteristics and risk factors of acute kidney injury due to flurbiprofen axetil. Results Among the 116 097 hospitalized patients who used flurbiprofen axetil, there were 815 positive cases of acute kidney injury, with an incidence of 0.70%. The results of the causal correlation evaluation were predominantly “probable”, with 692 cases (84.91%). The severity staging of positive cases was predominantly stage 1, with 449 cases (55.00%). The outcome of regression was mostly improvement, with 556 cases (68.22%). The departments involved were predominantly those of hepatobiliary surgery, with 575 cases (70.55%). Combined anemia (OR=2.30; 95%CI: 1.80~2.94), lower baseline eGFR (OR=1.01; 95%CI: 1.01~1.02), and co-administration of diuretics (OR=3.80; 95%CI: 3.01~4.81) were associated with a higher risk of acute kidney injury. Conclusion The incidence of flurbiprofen axetil-associated acute kidney injury is episodic. Clinical use of the drug should be monitored in patients with combined anemia, lower baseline eGFR, and co-administration of diuretics. References | Related Articles | Metrics

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Pharmaceutical care for a case of severe skin ulcer and corneal perforation caused by erlotinib hydrochloride tablets YUAN Qi, WANG Yingxian, CHEN Siying, YOU Haisheng 2023, 20(2): 206-208.  DOI: 10.19803/j.1672-8629.20211034 Abstract ( 159 )   PDF (1241KB) ( 160 )   Objective To optimize medication monitoring by clinical pharmacists and improve the role of therapeutic drug monitoring (TDM) via observation and follow-up of one case of adverse reactions caused by oral erlotinib. Methods Soon after one patient with lung cancer developed skin ulcer and corneal perforation following treatment with oral erlotinib, clinical pharmacists gave pharmaceutical care using evidence-based pharmacy and TDM. Results Through adjustment of the individualized medication regimen, symptomatic and supportive treatment of adverse reactions, the pain of the patient was significantly relieved, although her skin ulcer and corneal perforation were not cured. Conclusion In the course of medication for cancer patients, clinical pharmacists can use their expertise and knowledge to assist clinicians in providing individualized pharmaceutical care for patients, and contribute to rational clinical use of drugs. References | Related Articles | Metrics

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Analysis of one case of hemorrhagic goiter caused by aspirin tablets in one patient with coronary heart disease DING Qian, LI Boyu, ZHANG Qingxia 2023, 20(2): 209-212.  DOI: 10.19803/j.1672-8629.20211205 Abstract ( 187 )   PDF (1271KB) ( 176 )   Objective To study the effect of aspirin on the thyroid gland. Methods By analyzing one case of hemorrhagic goiter caused by aspirin, the correlations between medication and adverse drug reactions were investigated. Results Before the patient took aspirin, ultrasound of the patient’s thyroid gland showed multiple nodules and normal thyroid function. Twenty-four days after taking the medicine, the patient’s neck became increasingly swollen, and the thyroid ultrasound showed blood flow signals. After four months, she came back to see a doctor and a pharmacist, both of whom suggested discontinuing aspirin and rechecking thyroid function. Ten days after drug withdrawal, the swelling of the neck gradually shrank. More than one month later, the swelling completely subsided. No blood flow signal was found by thyroid ultrasound. Conclusion Goiter among patients taking aspirin may be caused by aspirin-related bleeding, which should attract the attention of doctors and pharmacists. It is suggested that patients taking aspirin should have their thyroid function examined and receive thyroid ultrasound examination in case of goiter, especially those with previous thyroid diseases. References | Related Articles | Metrics

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Analysis of one case of acute drug-induced liver injury caused by Shangfengting capsules LI Xiaojuan, ZHANG Aiwu, WEI Ying 2023, 20(2): 213-214.  DOI: 10.19803/j.1672-8629.20210849 Abstract ( 145 )   PDF (1152KB) ( 141 )   Objective To identify the components of Shangfengting capsules that may cause liver injury so as to provide reference for clinical rational drug use. Methods One case of liver injury caused by Shangfengting capsules was reported and the correlation between liver injury and the main components of this drug was analyzed. CNKI, Wanfang and VIP databases were searched for related literature that was published between inception and July 19, 2021. Results There were no related reports about liver injury caused by Tantanting capsules, but the ephedra in the formula could cause hepatocellular liver injury, and the mechanism was not clear. Conclusion Ephedra may lead to liver injury, so clinicians and pharmacists should manage to ensure the rational use of drugs to reduce and prevent liver injury. References | Related Articles | Metrics

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Analysis of one case of QT prolongation induced by palbociclib capsules RAN Tuoyao, LI Chao 2023, 20(2): 215-218.  DOI: 10.19803/j.1672-8629.20210977 Abstract ( 118 )   PDF (1216KB) ( 125 )   Objective To analyze one case of QT interval prolongation caused by palbociclib capsules in our hospital so as to provide reference for clinical rational drug use. Methods To report a case of QT prolongation in a breast cancer patient receiving cyclin-dependent kinase 4/6 (CDK4/6) inhibitor (palbociclib). Results and Conclusion Palbociclib may cause QT prolongation because of individual differences or combined use with other drugs or foods, so pharmaceutical care related to cardio toxicity during medication is required, and the effect of foods or other drug components on liver drug enzymes deserves attention. If possible, blood drug concentrations should be monitored to reduce adverse reactions. References | Related Articles | Metrics

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Analysis of one case of green urine caused by Indigo Naturalis NEI Qian, HUANG Ailing, ZHANG Hongcai, ZHAO Jue, ZHANG Delai, XIE Wen 2023, 20(2): 219-220.  DOI: 10.19803/j.1672-8629.20210265 Abstract ( 151 )   PDF (1146KB) ( 128 )   Objective To retrospectively study the possible causes of rare green urine in order to provide reference for clinical diagnosis and treatment. Methods The clinical data about one patient who had been hospitalized because of fever, cough and discomfort, and green urine after taking Indigo Naturalis, was reported and analyzed with a literature review. Results The patient’s urine routine examination and other related laboratory examinations showed no abnormalities, but chromatographic analysis of the urine revealed Indigo Naturalis. After the patient was told to stop using traditional Chinese medicine and drink plenty of water, the urine returned to normal light yellow. Conclusion Such elements of traditional Chinese medicines as Indigo Naturalis might cause urine to turn green by staining, but this change is usually harmless and needs to be distinguished from other pathological conditions. References | Related Articles | Metrics

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Analysis of one case of double knee joint pain induced by linezolid tablets WU Yanyan, HU Xuelian, DAN Chonghui 2023, 20(2): 221-224.  DOI: 10.19803/j.1672-8629.20220015 Abstract ( 237 )   PDF (1259KB) ( 183 )   Objective To analyze new adverse reactions-double knee joint pain-caused by linezolid in order to provide reference for related clinical pharmaceutical care. Methods The causes of double knee joint pain in a 39-year-old female patient were analyzed who had suffered mycobacterium abscess infection after resection of intervertebral schwannoma and taken oral linezolid tablets 0.6 g, oral clarithromycin tablets 0.5 g, and oral moxifloxacin tablets 0.4 g. Drugs that might have caused joint pain were identified using the Naranjo’s assessment scale. Results The pain and discomfort of knee joint in both legs were attributed to linezolid, and considered new adverse reactions caused by linezolid. Conclusion Pharmacists should be alert to new adverse reactions caused by linezolid and give high-quality pharmaceutical care while watching out for such marrow suppression as leukopenia caused by linezolid. References | Related Articles | Metrics

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Research progress in drugs for respiratory virus and anti-respiratory virus ZHOU Lirun, CUI Xiaolan, SHI Yujing 2023, 20(2): 225-230.  DOI: 10.19803/j.1672-8629.20211002 Abstract ( 139 )   PDF (1381KB) ( 174 )   Respiratory viruses pose a great threat to human life and health, which are characterized by strong infectivity, fast transmission and proneness to large-scale transmission. In clinical practice, more than 90% of acute upper respiratory tract infections are caused by viral infections. When a virus invades the human body, it causes upper respiratory tract symptoms such as cold, runny nose and sore throat before inducing lower respiratory tract symptoms such as bronchitis and pneumonia, which can lead to death in serious cases. The recent years have witnessed the outbreak of SARS, influenza virus, H1N1, avian influenza to COVID-19, making viral infections frequent. Seasonal and pandemic viral infections are a major cause of morbidity and mortality worldwide, which brings about huge economic losses to people. While vaccination can effectively prevent a pandemic, vaccines take time to be updated because respiratory viruses are prone to mutation. Drug therapy is the main means to contain the spread of respiratory viruses. In this paper, the achievements in anti-respiratory viruses are expounded from different perspectives, which is expected to provide reference for effective prevention and treatment of respiratory viruses. References | Related Articles | Metrics

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Research progress in chemical constituents and pharmacological effects of phytoecdysterone from Cyanotis arachnoidea HU Jingnan, FENG Yu, TIAN Yilong, WANG Xinguo, NIU Liying 2023, 20(2): 231-235.  DOI: 10.19803/j.1672-8629.20210466 Abstract ( 173 )   PDF (1368KB) ( 85 )   Cyanotis arachnoidea, a type of Yi medicine, is a perennial herb belonging to the Cyanotis D. Don of Commelinaceae. Phytoecdysterone is one of the main active components of Cyanotis arachnoidea. So far, phytoecdysteroids, phytosterol, phytosterone glycoside, fatty acid, terpene and volatile oil have been identified as the main chemical constituents of Cyanotis arachnoidea. Among these chemical constituents, phytoecdysterone has the most significant content. Phytoecdysterone has a wide range of biological activities, such as anti-inflammatory and anti-tumor properties, protection of the nervous system, reduction of blood glucose and lipid, and protection of cardiovascular and skeletal systems and organs. In this paper, the phytoecdysterone constituents of Cyanotis arachnoidea and the biological activities of phytoecdysterone were summarized in order to provide reference for the development and utilization of Cyanotis arachnoidea. References | Related Articles | Metrics

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Advances in studies on post-market safety data sources and signal detection for medical devices ZHAO Yan, LI Dong, CHENG Yinjie, JIANG Bin, ZHAO Yifei, DONG Fang, YUAN Jing 2023, 20(2): 236-240.  DOI: 10.19803/j.1672-8629.20220562 Abstract ( 273 )   PDF (1291KB) ( 388 )   Objective To summarize the recent research advances in post-market safety data sources and signal detection for medical devices so as to provide evidence for post-market regulation of medical devices. Methods Literature on post-market safety signal detection for medical devices was searched to keep track of the latest progress in post-market safety data sources and signal detection methods. Results and Conclusion With the rapid development of information technology, such real-world data as medical insurance claims, electronic health records, and registry data have become the main sources of data on post-market safety signal detection for medical devices. With the expansion of sources of data, multiple signal detection approaches have been developed and applied in post-market safety surveillance for medical devices. Social media data and data automatically collected by medical devices are also emerging sources of data. In the course of signal detection for medical devices, a variety of methods are used, including disproportionality methods, pharmacoepidemiology approaches, and machine learning methods. To reduce selection bias in observational studies, propensity scores are often applied in pharmacoepidemiology studies in order to evaluate the safety of medical devices more effectively. References | Related Articles | Metrics