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    15 June 2024, Volume 21 Issue 6 Previous Issue    Next Issue

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    Research progress in roles of ginseng combined with Radix Aconiti Carmichaeli in reducing toxicity and increasing efficiency in myocardial cells
    LI Hongchang, GE Yunxuan, WANG Ningning, ZHOU Wei, WANG Yuguang, MA Zengchun, GAO Yue
    2024, 21(6): 601-605. 
    DOI: 10.19803/j.1672-8629.20230681

    Abstract ( 262 )   PDF (1494KB) ( 104 )  
    Objective To study the mechanisms by which ginseng combined with Radix Aconiti Carmichaeli can reduce toxicity while improving efficacy in terms of chemistry, pharmacokinetics, drug metabolism, interactions between components and biological mechanisms. Methods The “dose- toxicity-time-effect” relationship was established based on drug dosage and molecular pathways. Energy metabolism and calcium overload were studied to find out whether they were involved in pharmacological and toxic effects, respectively. The toxicity conversion window of aconitine was analyzed while the toxicity threshold was predicted using physiologically based pharmacokinetic models (PBPK) and in vivo reverse dosimetry. The early toxicity dose of traditional Chinese medicine, impacts of drug metabolic enzymes and transporters on the in vivo disposal process of drugs, and drug interactions were explored. Results It was found that the combination of ginseng with Radix Aconiti Carmichaeli could reduce the concentration of aconitine through pharmacological mechanisms and antagonize toxic targets through toxicological mechanisms, thus acting as both a threat and a killer in the compatibility theory of “seven emotions and harmony”. Conclusion The study has shed light on the role of ginseng combined with Radix Aconiti Carmichaeli in reducing toxicity and increasing efficiency, and contributed to the compatibility theory about the “seven emotions and harmony”.
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    Effect of hypaconitine of radix aconiti carmichaeli on hERG channels in cardiac myocytes via miR-134 regulation
    GE Yunxuan, WANG Yuguang, ZHANG Zhuo, MA Zengchun, GAO Yue
    2024, 21(6): 606-610. 
    DOI: 10.19803/j.1672-8629.20230682

    Abstract ( 71 )   PDF (1985KB) ( 78 )  
    Objective To explore the mechanism by which hypaconitine regulates myocardial cell toxicity through miRNA-hERG pathway. Methods The gene expression level was measured by real-time fluorescence quantitative PCR, the protein expression was determined by Western blot, and hERG currents were recorded by the whole cell patch-clamp technique. Results Three major diester alkaloids could inhibit hERG protein and gene expressions, among which hypaconitine had the strongest inhibitory effect in a dose-dependent manner. Hypaconitine promoted the expression of miR-134 most significantly and the weakened inhibitory effect of hypaconitine on hERG protein gene was exhibited after the expression of miR-134 was decreased. Conclusion Hypoaconitine can decrease the rate of hERG channel inactivation and the expression of hERG by upregulating the expressions of related miRNAs. The inhibitory effect of hypaconitine on hERG may be an important cause of radix aconiti carmichaeli cardiotoxicity.
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    Clinical characterization and mechanism exploration of Fructus Psoraleae-induced hepatotoxicity in zebrafish
    AO Ting, WANG Ningning, ZHOU Lei, DENG Huifang, YANG Xingxin, ZHOU Wei, SHEN Pan, GAO Yue
    2024, 21(6): 611-616. 
    DOI: 10.19803/j.1672-8629.20240317

    Abstract ( 62 )   PDF (2408KB) ( 74 )  
    Objective To investigate the effects of Fructus Psoraleae (FP) in accordance with clinical medicinal characteristics on the liver of zebrafish based on the proteome and its potential hepatotoxic mechanism. Methods Adult zebrafish were continuously treated with low, medium, and high concentrations of FP decoction (0.025, 0.050, 0.100 mg·mL-1) for 21 days. Changes in zebrafish body weight, liver histopathology, and levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the serum detected by enzyme-linked immunosorbent assay (ELISA) were compared. Potential hepatotoxic mechanisms were studied based on identified liver proteome through cluster and pathway enrichment analysis, and molecular docking was used to explore potential toxic targets of the main hepatotoxic components of FP. Results Zebrafish treated with FP decoction showed a significant decrease in body weight compared to the control group, with a more pronounced weight loss as the concentration increased. The levels of ALT and AST were significantly elevated in the Angelica sinensis treated group, with a dose-dependent effect (P < 0.05). Hematoxylin-eosin (HE) staining results showed disordered arrangement of liver cells, increased gaps, and phenomena such as steatosis and immune cell infiltration in the liver tissues of the FP-treated group compared to the control group, with the severity of the lesions worsening with increasing concentration. Cluster and functional enrichment analysis of the proteome indicated that FP affected the expression of lipid and energy metabolism-related proteins, including acetyl-CoA acetyltransferase 1 (acat1), 3-hydroxyacyl-CoA dehydrogenase (ehhadh), succinate dehydrogenase (sdha) and succinate dehydrogenase (sdhb) in the zebrafish liver, and molecular docking revealed the potential of the main hepatotoxic components in FP to bind to these proteins. Conclusion Long-term Fructus Psoraleae administration causes hepatic lipid metabolism disorders, ultimately resulting in hepatotoxicity characterized by steatosis, with the potential toxicity mechanism involving abnormal expression of lipid and energy metabolism-related proteins induced by main hepatotoxic compounds in FP.
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    Therapeutic effect and immune mechanism of artemisia annua L. ointment on mouse eczema models
    XIE Zhiqiang, YUAN Jiqiao, LI Jialin, LIU Zhengyue, WANG Manyuan
    2024, 21(6): 617-624. 
    DOI: 10.19803/j.1672-8629.20240033

    Abstract ( 58 )   PDF (2238KB) ( 58 )  
    Objective To evaluate the therapeutic effect of Artemisia annua L. ointment against eczema and explore its potential immunomodulatory mechanism. Methods Seventy KM mice were randomly divided into seven groups: normal control group, model group, positive drug group, artemisia annua L. ointment low (0.4 g·g-1), medium (0.8 g·g-1), and high (1.6 g·g-1) dose groups, and drug control group. Except for the normal control group and the drug control group, all the mice were induced with eczema by applying 2,4-dinitrochlorobenzene on the abdominal and ear skin. During treatment, the mice in each treatment group were topically administered with the corresponding drugs once a day for 12 days. The degree of ear swelling and thickness change were measured, and the ear allergic reactions were scored. The ear skin tissue was collected for HE staining and histopathological examination. The organ index of each group of mice was calculated while the levels of inflammatory cytokines such as interferon(IFN-γ) , interleukin-2 (IL-2), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-4 (IL-4) in serum were quantified using the ELISA method. Results On the 15th day, the difference in ear thickness in the model group was significantly increased compared with the normal control group (P<0.001), and the ear anaphylaxis score was significantly increased (P<0.001). Compared with the model group, the ear thickness of mice in low and medium dose groups of artemisia annua L. ointment decreased significantly (P<0.05), and the ear anaphylaxis score decreased in a dose-dependent manner, but the difference was insignificant. On the 19th day, compared with the normal control group, the ear thickness difference in the model group was significantly increased (P<0.001), the ear anaphylaxis score was significantly increased (P<0.001), and the serum levels of IFN-γ、IL-2 and TNF-α were significantly decreased (P<0.001), but the levels of IL-6 and IL-4 were significantly increased (P<0.001). Compared with the model group, there was no significant difference in ear thickness between the low and medium dose groups, and the ear allergy response score decreased in a dose-dependent manner, but the difference was not significant. Serum IFN-γ levels (P<0.001) and TNF-α levels (P<0.05) were significantly increased in the low dose group, and IL-2 levels were increased but the difference was not significant. The levels of IL-6 (P<0.01) and IL-4 (P<0.05) were significantly decreased, but serum levels of IFN-γ (P<0.001), IL-2 (P<0.05) and TNF-α (P<0.05) were significantly increased in artemisia annua L. ointment medium dose group, while IL-6 (P<0.001) and IL-4 levels (P<0.001) were significantly decreased. At the end of the experiment, the ear swelling of the model group was significantly increased compared with the normal control group (P<0.001), the ear skin tissue showed obvious inflammatory cell infiltration, and the spleen index was significantly increased (P<0.01). Compared with the model group, ear swelling of mice in low and medium dose groups was significantly improved (P<0.001), inflammatory cell infiltration in ear skin tissue of mice in the low dose group was reduced, and the spleen index was significantly decreased (P<0.05). Conclusion artemisia annua L. ointment has a significant therapeutic effect against eczema, and its mechanism may be related to the regulation of the balance of Th1/Th2 cell functions and the inhibition of allergic inflammatory reactions.
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    Exploratory study of cytokine release syndrome in vitro
    FU Yingshuang, LI Shuangxing, JIANG Hua, QU Zhe, HUO Guitao, YANG Yanwei, ZHANG Di, HUANG Ying, LI Bo, LIN Zhi
    2024, 21(6): 625-631. 
    DOI: 10.19803/j.1672-8629.20240149

    Abstract ( 52 )   PDF (1477KB) ( 61 )  
    Objective To establish an in vitro evaluation method of cytokine release syndrome(CRS), and explore the cell density, positive drug types and concentrations of the test system. Methods Peripheral blood mononuclear cells (PBMC) were stimulated with CD3 antibody (OKT3) (0.1~5μg), OKT3 (0.1~1μg) + CD28 antibody (anti-CD28) (1 and 2 μg·mL-1), phorbol-12-myristate-13-acetate (PMA) (10~100 ng·mL-1), and PMA (10~100 ng·mL-1) + ionomycin (ION) (1 and 5 μg·mL-1) for 48 h, respectively. The proliferation of PBMC was assessed by the CCK-8 method to determine the optimal cell density and drug concentration. There were seven groups in the experiment: Control group, OKT3 0.1μg+anti-CD28 1 μg·mL-1 group, OKT3 0.5μg+anti-CD28 1μg·mL-1 group, OKT3 1μg+anti-CD28 1μg·mL-1 group, PMA 10 ng·mL-1+ION 1μg·mL-1 group, PMA 25 ng·mL-1+ION 1μg·mL-1 group and PMA 50 ng·mL-1+ION 1μg·mL-1 group. The cell supernatant was collected after 48 h of exposure to the respective treatments and cytokine IL-6 and IFN-γ was detected by ELISA. Results Compared with the control group, both OKT3 and PMA induced significant proliferation of medium density and high density PBMC, and OKT3 and PMA induced cell proliferation at all doses. The combination of drugs produced a stronger cell activation effect than the positive drug alone. Compared with the control group, the release of IL-6 and IFN-γ from PBMC was significantly increased under OKT3 (0.1~1μg) +anti-CD28 (1μg·mL-1) treatment. Under PMA (10~50 ng·mL-1) +ION (1μg·mL-1), the secretion of IFN-γ by PBMC was significantly increased compared with the control group, and under PMA (25-50 ng·mL-1) +ION (1μg·mL-1), the secretion of IL-6 by PBMC was significantly increased compared with the control group. Conclusion The study determines the cell density, positive drug types and concentrations, and drug combination of CRS risk assessment methods for PBMC in vitro.
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    Quality evaluation of desmopressin tablets and injection
    SUN Yue, HU Xinyue, LI Jing, ZHANG Wei, DING Xiaoli, ZHANG Hui, LIANG Chenggang
    2024, 21(6): 632-637. 
    DOI: 10.19803/j.1672-8629.20230385

    Abstract ( 51 )   PDF (2536KB) ( 74 )  
    Objective To evaluate the quality of listed products of desmopressin tablets and its injection, and provide data for the revision of drug quality standards and for drug quality control and supervision. Methods Based on statutory inspection and exploratory research, 20 batches of desmopressin tablets and 16 batches of desmopressin injection were inspected before exploratory research was carried out, such as methodological research on related substances of tablets, dissolution analysis of tablets, stability of tablets and injections. Results The qualification rate of statutory inspection for 20 batches of desmopressin tablets and 16 batches of desmopressin injection was 100%. The exploratory research optimized the determination methods of related substances in tablets and the interference of the excipient povidone in detection was eliminated. The dissolution of tablets at home and abroad was investigated and the results showed that the dissolution behavior was similar. The stability of the tablets and injection was investigated, and the structure of impurities in the injection was confirmed, which were mainly 5-site deamidation desmopressin and optical isomer impurities. Conclusion The quality of desmopressin tablets and their injections is good, and there are still some problems with the quality standards, which need to be improved.
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    Effect of ethanol on release behavior of glipizide controlled release tablets by HPLC
    SU Hai, ZAN Mengqing, NIU Jianzhao, MA Lingyun, LIU Qian
    2024, 21(6): 638-643. 
    DOI: 10.19803/j.1672-8629.20230412

    Abstract ( 30 )   PDF (1644KB) ( 51 )  
    Objective To comparatively study the alcohol-induced dose dumping in glipizide controlled-release tablets from different manufacturers and their reference formulation according to the National Medical Products Administration (NMPA) guidelines. Methods The in vitro release of glipizide from generic and reference formulations at different concentrations of ethanol was examined using high-performance liquid chromatography (HPLC). Dissolution profiles were meticulously generated, and the relative change in the rate of dissolution due to ethanol was used as an index to assess its effect on drug release kinetics. Additionally, the similarity in in vitro release patterns across various formulations was quantitatively evaluated by calculating the similarity factor (f2). Results It was observed that the in vitro release profiles of generic formulations and the reference formulation underwent minimal changes at ethanol concentrations of 5% and 20%, with a noticeable increase at 40% ethanol, much like the release observed in a hydrochloric acid medium without ethanol (f2>50), indicating that the in vitro release behavior of the generic formulations closely paralleled that of the reference formulation. Conclusion The generic formulations meet the quality standards for consistency evaluation. Ethanol concentrations ranging from 0% to 40% do not significantly affect the in vitro release behavior of glipizide controlled-release tablets. The presence of hydrophilic excipients and the unique push-pull osmotic pump structure within the formulation may play critical roles in mitigating the risk of alcohol-induced dose dumping. These findings can help predict appropriate dosing and assess the safety risk associated with consuming glipizide alongside alcoholic beverages.
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    Quality evaluation of insulin glargine injections
    DING Xiaoli, HU Xinyue, WANG Xuelei, SUN Yue, LI Jing, ZHANG Hui, Liang Chenggang, WANG Yan
    2024, 21(6): 644-650. 
    DOI: 10.19803/j.1672-8629.20230460

    Abstract ( 65 )   PDF (2352KB) ( 69 )  
    Objective To evaluate the quality of and problems with insulin glargine injections, and study the validity and rationality of drug specifications so as to provide reference for evaluation and supervision of safety. Methods Insulin glargine injections were sampled and evaluated nationwide. The related substances and contents of the samples were tested using the stipulated standard method. The stability of injections and the increase of related substances of injections in usewere tested via exploratory research, and the structures of main related substances were confirmed by LC-MS/MS. According to the results, the limits of related substances specified in enterprise standards and the current Chinese pharmacopoeia standard were evaluated. Results The qualified rate of 48 batches of insulin glargine injections was 100%. Exploratory research showed that the number or contents of related substances in some of the insulin glargine injections were higher, and the contents of maximum related substances in some of the injections were at risk of exceeding the limit of enterprise standards. Conclusion The overall quality of insulin glargine injections is good. Related enterprises should formulate rational and precise limits of related substances in line with the Chinese pharmacopoeia by investigating the increase of relevant substances on the shelf or in use (especially near-effect products).
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    Therapeutic effect of Jingzhui Kangfu pills against osteoarthritis induced by proteoglycan in mice
    LIU Yang, FAN Zheng, WANG Honglei, YANG Ying, GUO Qi, CHANG Xinyu, HAN Lijuan, LI Wenzhe, WU Jiankun
    2024, 21(6): 651-654. 
    DOI: 10.19803/j.1672-8629.20230738

    Abstract ( 26 )   PDF (1679KB) ( 49 )  
    Objective To study the therapeutic effects of Jingzhui Kangfu pills against proteoglycan-induced osteoarthritis in mice and to provide data for increasing the indications and clinical applications of this drug. Methods Balb/c mice were randomly divided into the normal group, model group, high dose(6, 3 g·kg-1·d-1) group and low dose group. All the mice (except the normal group) were intraperitoneally injected with 0.2 mL DDA adjuvant (containing 100μg proteoglycan) to establish a model. The normal group was given 0.2 mL normal saline. After initial immunization, arthritis was assessed and weight was monitored every 2 weeks until the 14th week. The histopathologic morphology of joints was observed via HE staining and Safranine O-Fast Green staining. Levels of serum inflammatory factors IL-1β, IL-6, TNF-α and IL-17A were determined by ELISA. Results Jingzhui Kangfu pills could significantly mitigate osteoarthritis in mice, and lower the score of arthritics and degree of swelling. Under microscopic observation, Jingzhui Kangfu pills could protect the joint tissue of mice and reduce inflammatory infiltration and significantly reduce the levels of serum inflammatory factors IL-1β, IL-6, TNF and IL-17A. Conclusion Jingzhui Kangfu pills can improve proteoglycan-induced osteoarthritis in mice.
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    Roles of Foshao granules in regulating gut microbiota and lactase activity in mice
    LI Shuran, GUO Shanshan, ZHAO Ronghua, BAO Lei, SUN Jing, GENG Zihan, BAO Yanyan, PANG Bo, CHEN Mengping, LYU Yaozhong, WANG Zhenzhong, CUI Xiaolan, WANG Hongmei
    2024, 21(6): 655-659. 
    DOI: 10.19803/j.1672-8629.20230300

    Abstract ( 28 )   PDF (1422KB) ( 57 )  
    Objective To study the effect of Foshao granules on the gut microbiota and lactase activity of mice. Methods Experimental rats were randomly divided into seven groups according to their body weight: the normal control group, model control group, domperidone control group (12 mg·kg-1), Sini powder control group (3 g·kg-1), Foshao granules high dosage group (48 g crude drug·kg-1), medium dosage group (24 g crude drug·kg-1), and low dosage group (12 g crude drug·kg-1), with 10 mice in each. A model of flora imbalance mice was induced by a mixture of cefradine capsules and gentamycin sulfate (2 : 1). By measuring the number of total anaerobic bacteria, Lactobacillus, bifidobacteria, Escherichia coli, the extent to which Foshao granules regulated the gut microbiota and lactase activity of mice was evaluated. Results Foshao granules could significantly increase the number of total anaerobic bacteria (P <0.01), Lactobacillus (P <0.01), bifidobacteria (P <0.01) and Escherichia coli(P <0.01), and elevated the colonic mucosal lactase activity. Conclusion Foshao granules can improve flora imbalance and the reduction of lactase activity caused by cefradine and gentamicin sulphate. This study is expected to provide data for clinical applications of Foshao granules.
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    A real-world safety study of 3 010 cases of Qizhitongluo capsule
    PAN Zhiyu, ZHU Jian, YU Yanan, LIU Jun, JIANG Yanhua, QIAN Zhenzhen, WU Guang, WANG Zhong, WU Hongli, JING Zhiwei
    2024, 21(6): 660-665. 
    DOI: 10.19803/j.1672-8629.20240050

    Abstract ( 99 )   PDF (1436KB) ( 119 )  
    Objective To explore the clinical safety of Qizhitongluo capsule in the real world after its launch. Methods The safety of Qizhitongluo capsule was evaluated in all patients using the capsules from November 24, 2020 to November 25, 2022 at 19 institutions in 6 provinces (Henan, Shanxi, Guangxi, Liaoning, Shandong, and Heilongjiang) by means of drug-derived prospective centralised surveillance and nested case-control methods. Results A total of 3010 patients were included, and 21 cases of adverse reactions occurred, accounting for 0.7%, including 15 cases of gastrointestinal diseases, 2 cases of various neurological disorders, 2 cases of psychiatric disorders, and 2 cases of various musculoskeletal and connective tissue disorders, which were mainly manifested as abdominal discomfort, diarrhoea, oral ulcers, headache, and insomnia, etc., and no serious adverse reactions occurred. The results of multifactorial analysis showed that the occurrence of adverse reactions was related to the dosage frequency of Qizhitongluo capsules, and the frequency of dosage exceeding the dosage frequency recommended by the instruction manual would increase the incidence of adverse reactions. Conclusion The incidence of adverse reactions of Qizhitongluo capsules was 0.70%, mostly in gastrointestinal diseases, and also in psychiatric diseases and musculoskeletal and connective tissue disease.
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    Risks of liver injury caused by Shiduqing preparations
    SHAO Bo, XU Lili, ZHU Lan, LIU Shuo, WAN Hao, HUANG Guangrui
    2024, 21(6): 666-670. 
    DOI: 10.19803/j.1672-8629.20240137

    Abstract ( 78 )   PDF (1363KB) ( 105 )  
    Objective To analyze the risks of liver injury posed by Shiduqing preparations and provide reference for proper clinical use. Methods Literature about adverse reactions related to Shiduqing preparations in China’s adverse drug reaction monitoring database (collected between 2004 and 2023) and domestic database (from inception to December 31, 2023) was sorted out and analyzed. Results The National Adverse Drug Reaction Monitoring System Database documented 24 cases of adverse reactions related to liver and gallbladder damage and involving Shiduqing preparations. No adverse reactions related to hepatobiliary damage were found in clinical studies. The adverse reactions mentioned in individual reports were drug induced liver disease and liver injury. Conclusion Clinicians should be alert to the risk of liver injury when Shiduqing preparations are used in clinic. The awareness of safe and proper medications should be raised, and medications monitored. At the same time, drug marketing authorization holders should strengthen pharmacovigilance and provide guidance to ensure safe medication.
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    Systematic evaluation of clinical features and prognostic outcomes of rifampicin-induced hemolytic anemia
    GAO Xu, PENG Jin’e, FAN Zibo, ZHANG Wei
    2024, 21(6): 671-676. 
    DOI: 10.19803/j.1672-8629.20240034

    Abstract ( 117 )   PDF (1417KB) ( 94 )  
    Objective To summarize the epidemiology, clinical features and prognostic outcomes of rifampicin-induced hemolytic anaemia, and to provide data for the prevention and treatment of rifampicin-induced hemolytic anaemia. Methods A systematic evaluation was conducted by searching such databases as Pubmed, Web of Science, Proquest, Ovid, China Knowledge, Wanfang data, Wipo, and SinoMed. Clinical cases with confirmed diagnosis of rifampicin-induced haemolytic anaemia reported before December 31, 2023 were collected. Results A total of 62 pieces of literature were included in the evaluation, consisting of 45 in Chinese and 17 in English. Among the 69 patients with rifampicin-induced haemolytic anaemia, the age ranged from 7 months to 80 years. There were 35 male cases (50.72%) and 34 female ones (49.28%). Forty-nine cases were reported in China and the rest abroad. Haemolytic anaemia occurred in 42 cases (60.87%) after the first dose of rifampicin, in 24 cases (34.78%) after intermittent use of the drug, but the time of onset was unknown in three cases (4.35%). Common clinical manifestations included fever, chills, nausea, and vomiting, often accompanied by elevated white blood cells, liver aminotransferases, bilirubin, creatinine, and a significant decrease in haemoglobin. Treatments mainly involved immediate drug withdrawal, oxygenation, fluid replacement, maintenance of water and electrolyte acid-base balance, diuresis, alkalinisation of urine, application of hormones, anti-allergic drugs, hepatoprotective drugs, blood transfusion, haemodialysis, plasma exchange, and peritoneal dialysis. After treatment, 52 patients (75.36%) showed improvement and were discharged, 10 patients (14.49%) died, and the outcome was unknown in 7 patients (10.14%). Conclusion Rifampicin-induced haemolytic anaemia has been reported in recent years and can strike patients of any age, and intermittent use of rifampicin is more likely to result in haemolytic anaemia. The early symptoms of haemolytic anaemia are mostly influenza symptoms and gastrointestinal discomfort. Prompt treatment usually has a good prognosis, but the disease may progress rapidly and may to death in severe cases.
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    Exploring the scientific connotation of Mongolian Medicine pharmacovigilance based on ancient Mongolian Medical literature
    ALATENG Hua, GAO Lei, ZHANG Xiaomeng, ZHANG Bing
    2024, 21(6): 677-682. 
    DOI: 10.19803/j.1672-8629.20230743

    Abstract ( 57 )   PDF (1282KB) ( 68 )  
    Objective To study the ancient Mongolian Medical literature from the perspective of pharmacovigilance, explain the theoretical connotation of Mongolian Medicine pharmacovigilance, and provide a reference for further research on the safety evaluation and pharmacovigilance of Mongolian Medicine. Methods By combing through over 40 classic works of Mongolian Medicine and historical documents since the 4th century, the content related to pharmacovigilance was excavated, and the toxicity theory and characteristics of safe and rational drug use in Mongolian Medicine were analyzed. Results The study found that Mongolian Medicine attaches great importance to the duality of drugs, which means that drugs can bring harm to the human body while treating diseases. The Mongolian Medicine pharmacovigilance is mainly reflected in the following aspects: the understanding of toxicity, detoxification of poisoning, dietary taboos, living taboos, physical taboos, disease taboos, and other medication taboos; methods of reducing toxicity such as compatibility and processing; principles for controlling drug dosage and treatment duration; as well as the characteristics of dosage forms. Conclusion Mongolian people have a long history of understanding and using “toxicity”, coupled with the theoretical characteristics of Mongolian Medicine and clinical medication differences, the practice of safe and rational drug use is rich and unique. Exploring the scientific connotation of Mongolian Medicine pharmacovigilance has practical and far-reaching significance for guiding the rational use of Mongolian Medicine in modern clinical practice and inheriting traditional medicine.
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    Analysis of post-marketing adverse reactions of ametinib
    SUN Xuelin, DU Jiao, TAN Qin, HU Xin, ZHANG Yatong, ZHENG Li
    2024, 21(6): 683-686. 
    DOI: 10.19803/j.1672-8629.20240089

    Abstract ( 162 )   PDF (1363KB) ( 161 )  
    Objective To analyze the incidence of adverse reactions of the third-generation EGFR-TKI aumolertinib, and to provide reference for rational use of the drug in clinic. Methods PubMed, Embase, Web of Science, The Cochrane Library, CNKI, and WanFang Data and SinoMed database were searched to retrieve the literature on post-marketing adverse reactions of aumolertinib that was published from the inception to 16 January 2024 and to perform statistical analyses. Results A total of 12 articles were included in the study, and data on safety was collected from 263 patients. There were 246 adverse reactions caused by ametinib, which were mainly manifested as rash/acne-like rash (17.9%), increased transaminases (12.6%), onychomycosis (7.3%), haematological and lymphatic system disorders (6.1%), and generalized malaise (5.7%). A total of 11 adverse reactions ≥ grade 3 occurred, and the prognosis was good. Conclusion The adverse reactions of aumolertinib have diverse manifestations, and the effect on the skin and liver function is more obvious. Clinicians are advised to be alert to the occurrence of adverse reactions.
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    Safety signal analysis of antidepressants use in fetus and neonate based on US FAERS database
    SHI Guanhong, WANG Qi, SUN Hao, CHEN Yanjie, CHU Ziyan, JIANG Ao, TANG Zaixiang, LIU Jingfang
    2024, 21(6): 687-692. 
    DOI: 10.19803/j.1672-8629.20230789

    Abstract ( 151 )   PDF (1346KB) ( 142 )  
    Objective To mine and evaluate the risk signals of antidepressants use in fetus and neonate adverse events based on the database of the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), and provide reference for clinical rational drug use. Methods Filter primary suspect and second suspect antidepressants AE reports from 1th January 2004 to 31th December 2022 in FAERS database. Mine the signals of fetus or neonate adverse events with antidepressants via reporting odds ratio (ROR) and proportional reporting ratio (PRR). Results There are 14 492 cases of fetal and neonatal anomalies in the study, including 5 546 fetal abnormal cases and 8 946 neonatal abnormal cases. From drug aspect, there 68.97% foetal adverse signals and 56.35% neonatal adverse signals are selective serotonin reuptake inhibitors (SSRIs). From adverse event aspect, there 51.72% foetal adverse signals is related to amniotic fluid and 20.99% neonatal adverse signals is respiratory system disorders. Signals of Citalopram and Venlafaxine are highlighted after the second screening, which have adverse signals not specified in the label. Conclusion The overall signal characteristics of antidepressants are basically consistent with the existing safety data. However, some adverse events such as fetal amniotic fluid disorders and neonatal heart disorders are not listed in label through group analysis, which should be paid attention to in clinical use.
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    Pharmaceutical care of acute liver injury in a patient with colon cancer induced by irinotecan
    LIN Yanxin, LIU Yanhui, DONG Jing, YAO Jiachen, LI Wenyan
    2024, 21(6): 693-696. 
    DOI: 10.19803/j.1672-8629.20240009

    Abstract ( 96 )   PDF (1261KB) ( 95 )  
    Objective To explore the role of clinical pharmacists in the treatment of liver injury in tumor patients, and to provide reference for the involvement of clinical pharmacists in clinical practice. Methods Clinical pharmacists participated in the treatment of one case of acute liver injury caused by irinotecan in a colon cancer patient, analyzed the causes of acute liver injury, assessed the causal relationship between the drug and liver injury using the Roussel Uclaf Causality Assessment Method (RUCAM), and adjusted the treatment with liver-protecting drugs. Results By analyzing the correlation between acute liver injury and diseases and drugs, clinical pharmacists quickly recommended optimization of the treatment with liver-protecting drugs, and provided pharmaceutical care for the patient. After treatment, the patient’s liver function was significantly improved. Conclusion Prudent pharmacological monitoring of patients under chemotherapy by clinical pharmacists can help to reduce the incidence of adverse reactions, optimize the effect of drug therapy, and improve the level of rational clinical use of drugs.
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    One case of multiple organ failure caused by intravesical infusion of BCG vaccine
    XU Yuhang, GONG Qingmei, LUO Yuchen, WANG Zongyu, ZHANG Jian
    2024, 21(6): 697-699. 
    DOI: 10.19803/j.1672-8629.20240055

    Abstract ( 72 )   PDF (1213KB) ( 71 )  
    Objective To explore the pathogenesis of complications arising from bladder instillation of the BCG vaccine in order to provide data for clinical applications. Methods One case of multiple organ failure caused by intravesical instillation of the BCG vaccine was analyzed. Related literature was reviewed while the incidence, pathogenesis and clinical manifestations of this complication were analyzed. Results The patient was discharged from the hospital in better condition after symptomatic treatment, involving blood pressure elevation, anti-infection, anti-shock and anti-tuberculosis medications as well as rehydration. The related laboratory indicators of the patient improved. However, the possibility of disseminated tuberculosis could not be ruled out, and allergic reactions might also be involved, which needed to be studied. Conclusion Although the majority of patients are well tolerant of bladder instillation of the BCG vaccine, clinicians need to be alert to its the risk of sepsis.
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    One case of erythema multiforme drug eruption caused by donafenib tosilate tablets
    TANG Zhenju, LONG Xiaohuan, WANG Yijun, HUANG Yuteng, WANG Weiliang
    2024, 21(6): 700-702. 
    DOI: 10.19803/j.1672-8629.20230610

    Abstract ( 84 )   PDF (1176KB) ( 113 )  
    Objective To explore the clinical characteristics and mechanism of rare systemic skin adverse reactions caused by donafenib tosilate tablets (donafenib). Methods Rare skin toxicity caused by donafenib in a patient with gallbladder malignant tumor was analyzed while the manifestations and pathogenesis were summarized based on literature review. Results The clinical manifestations of this patient including atypical target erythema, pruritus and fever were similar to those of erythema multiforme drug eruption. After discontinuation of donafenib and treatment with hormone, human immunoglobulin and antihistamine drugs, the symptoms were significantly relieved. Conclusion Erythema multiforme drug eruption induced by donafenib is rare but severe, which deserves more attention. There have been no related reports at home and abroad. Donafenib is a derivative of sorafenib so that the pathogenesis is similar.
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    Evaluation of drug safety with multicenter real-world data
    WANG Chunnan, QIN Shiru, ZHANG Meng, SONG Haibo, LIU Junchang, LI Ge, SUN Feng
    2024, 21(6): 703-708. 
    DOI: 10.19803/j.1672-8629.20240016

    Abstract ( 180 )   PDF (1821KB) ( 144 )  
    Objective To explore the progress, hot spots, and developments of research on drug safety evaluation based on multicenter real-world data. Methods PubMed, Web of Science, and Scopus were searched for literature on drug safety evaluation using multicenter real-world data. Firstly, bibliometrix was used for visual analysis of the time the included literature was published and the distribution of countries and journals. In addition, the frequency, co-occurrence, and diachronic changes of keywords were displayed. Information on the target diseases, intervention drugs, research safety outcomes, real-world data sources, multicenter data sharing was retrieved. Results A total of 405 publications in 2004-2023 were included in the analysis, and the number of publications increased year by year. Research focused on pharmacological interventions in neoplasms treatment, including targeted drugs, chemotherapeutic drugs, glucocorticoids, immunological agents, oral anticoagulants and antiplatelet drugs for circulatory disorders. The keyword co-occurrence analysis found 10 keyword clusters, the top two of which involved safety and atrial fibrillation. The most important source of data was the registry (217/405, 53.5%) in these studies. Currently, most research centers shared data within the country, so research data mostly came from more than 10 institutions (158/280, 56.4%). Data was shared across countries in Europe in this field. Conclusion There is increasing research on drug safety evaluation based on multicenter real-world data. The related research covers a wide range, such as neoplasms and circulatory system diseases. Multicenter data sharing between countries is increasing. Advances in information technology can facilitate inter-country RWD information exchange. The more commonly used real-world data is registry data and hospital database information. Building a global and multicenter data management platform and sharing real-world multi-source data will catch on.
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    Functions of PXR/CAR-metabolizing enzyme/transporter detoxification system and research progress
    QIN Jiaqi, ZHANG Fan, LYU Dongxia, HE Zhen, WEI Yuhui
    2024, 21(6): 709-715. 
    DOI: 10.19803/j.1672-8629.20240065

    Abstract ( 75 )   PDF (1587KB) ( 60 )  
    Objective To outline the functions of and research progress in the nuclear receptor pregnane X receptor (PXR) and constitutive androstane receptor (CAR)-metabolic enzyme/transporter detoxification system. Methods The detoxification system of PXR/CAR-metabolic enzyme/transporter and its applications were reviewed in terms of the liver metabolic enzyme, liver and kidney transporter and PXR CAR-mediated drug detoxification. Results and Conclusion Drugs, as exogenous substances in the human body, may have toxicity and side effects, which is likely to cause injury when administrated improperly or with apparent toxicity. Drug metabolic enzymes and transporters are two pivotal factors in determining the process and exposure of drugs in vivo, making much difference to drug toxicity and detoxification. With the continuous deeping of research, PXR and CAR have been found to play a central regulatory role in metabolic enzymes and transporters related to drug detoxification. As a result, PXR and CAR can combine with their related drug metabolizing enzymes and transporters to constitute the most important defense detoxification system in vivo, the so-called PXR/CAR- metabolic enzymes/transporters detoxification system.
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    Effect of PPARγ in liver fibrosis and current development of its ligand drugs: research progress
    ZHAO Xiaolu, GAO Xiaoyang, ZHANG Chunyan, LI Mingqi, MA Yuehong
    2024, 21(6): 716-720. 
    DOI: 10.19803/j.1672-8629.20230537

    Abstract ( 69 )   PDF (1437KB) ( 47 )  
    Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear factor family activated by endogenous or exogenous ligands, which regulate adipogenesis and metabolism, inflammation and other transcriptional modulators of crosstalk such as factor signaling in fibrosis progression. They have become a promising therapeutic target in recent years. Hepatic fibrosis (HF) is a complex pathological change mainly caused by collagen deposition and extracellular matrix (ECM) increases due to various etiologies, in which activated hepatic stellate cells (HSCs) play a pivotal role. Studies on PPARs have found that the expressions of its isoform PPARγ in adipose tissue, macrophages and HSCs are involved in inflammation, which leads to the formation of liver fibrosis. The upregulation of PAARγ maintains HSCs in reversing liver fibrosis. The quiescent phenotype and the promotion of apoptosis of activated HSCs also make a difference, suggesting that ligand-activated drugs targeting PAARγ may play an important role in anti-fibrotic therapy.
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