Archive

15 January 2024, Volume 21 Issue 1 Previous Issue    Next Issue

---

For Selected:

Download Citations EndNote Ris BibTeX

Toggle Thumbnails

Select

Discovery and identification strategy for drug safety risks based on big data monitoring of adverse reactions GAO Yunjuan, ZHAO Xu, BAI Tiankai, BAI Zhaofang, WANG Jiabo, SONG Haibo, XIAO Xiaohe 2024, 21(1): 1-5.  DOI: 10.19803/j.1672-8629.20230772 Abstract ( 744 )   PDF (1327KB) ( 713 )   Objective To explore how to quickly discover and accurately identify drug safety risks from a vast number of adverse reaction reports from domestic and foreign Chinese and Western medicines. The aim is also to make scientific and effective predictions and control measures for these risks. Methods Drug-induced liver injury data was taken as an example, and the process of discovering, evaluating, confirming, and controlling risks associated with drugs were discussed. Results A preliminary exploration was conducted, leading to the establishment of an integrated strategy and method system for “large-scale adverse reaction monitoring and discovery - multi-model recognition and analysis- disease-symptom-toxicology verification.” This system has been successfully applied in identifying and analyzing drug-induced liver injury. Conclusion This strategy offers a fresh perspective for the continuous development and innovation of drug safety evaluation. It also provides technical support for ensuring public safety in medication and promoting the healthy development of the Chinese and Western medicine industry. References | Related Articles | Metrics

Select

Theoretical innovation and technological breakthroughs in the safety evaluation of traditional Chinese medicine: disease-syndrome-based toxicology BAI Zhaofang, ZHAN Xiaoyan, YAO Qing, CHEN Simin, ZHAO Xu, XIAO Xiaohe 2024, 21(1): 6-14.  DOI: 10.19803/j.1672-8629.20230787 Abstract ( 195 )   PDF (1754KB) ( 211 )   Objective To promote the scientific, rational and efficient application of disease-syndrome-based toxicology in the development of new traditional Chinese medicine drugs, the clinical safety evaluation of traditional Chinese medicine (TCM), and the formulation of safe and precise medicine countermeasures, and promote the healthy and sustainable development of TCM. Methods In combination with the application of disease-syndrome-based toxicology in practice, its extension and intension were comprehensively defined. Meanwhile, the new theories, methods and discoveries of TCM safety research based on disease-syndrome-based toxicology were systematically reviewed. Results The toxicity of TCM is mainly divided into two types: intrinsic toxicity and idiosyncratic toxicity. Due to the sporadicity, susceptibility and unpredictability of idiosyncratic toxicity, conventional toxicological models and methods are difficult to evaluate the idiosyncratic toxicity of TCM. Therefore, the author's team inherited and innovated the idea of "You Gu Wu Yun" in TCM theory, and proposed the theory and method of disease-syndrome-based toxicology for the first time in 2016, aiming to break through the limitations of conventional toxicological models and methods, scientifically clarify the influence of factors such as heredity, constitution, disease syndrome, and other factors on the safety of TCM, and solve the problem of evaluating the idiosyncratic toxicity of TCM. In recent years, based on the continuous improvement and optimization of the disease-syndrome-based toxicology theory and methodological system, the author's team used the clinical real-world and the in vivo and in vitro susceptibility model of disease and syndrome as the main evaluation model, and carried out the research on the identification of susceptible population, genetic mechanism analysis and risk prevention and control countermeasures of the idiosyncratic toxicity of TCM such as Polygonum multiflorum, Fructus Psoraleae and Herba Epimedii, which solved the problems of safety evaluation and risk prevention and control of a series of traditional “non-toxic” TCM. Conclusion Disease-syndrome-based toxicology can not only be used for the identification of susceptible populations, mechanism analysis, and risk prevention and control strategies of TCM with idiosyncratic toxicity, but also for the study of the “disease (syndrome)-dose-time-toxicity-effect” relationship and safe therapeutic window of TCM with intrinsic toxicity. References | Related Articles | Metrics

Select

Exploring new risk signals and susceptibility factors of traditional Chinese medicine-induced hepatotoxicity based on big data from adverse reaction monitoring GUO Longxin, GAO Yunjuan, WU Chengzhao, LONG Minjuan, ZHU Shengkai, SONG Haibo, ZHAO Xu, XIAO Xiaohe 2024, 21(1): 15-19.  DOI: 10.19803/j.1672-8629.20230779 Abstract ( 323 )   PDF (1290KB) ( 326 )   Objective To explore the method of discovering signals of hepatotoxicity risk in traditional Chinese medicine (TCM) based on national adverse reaction monitoring big data, preliminarily screen risky varieties, and analyze the susceptible factors of liver damage based on the “ Trielement Injury Hypothesis ” theory. Methods Retrospective analysis of adverse drug reaction (ADR) reports related to TCM-induced drug-induced liver injury (DILI) collected between 2012 and 2016. Identify suspicious TCM varieties and predict the susceptible factors for liver damage in these varieties. Results A total of 1 901 ADR reports（1 719 patients) of TCM-induced DILI were collected, and 237 suspicious TCM varieties were newly discovered. Traditional Chinese medicine used for anti-tumor purposes had the highest incidence of DILI. The oral route of administration accounted for the largest proportion (71.70%), with a median latency period of 13.00 days, and the majority of cases had a latency period of 0 to 7 days (34.46%). Analysis based on the “ Trielement Injury Hypothesis ”theory revealed that the TCM varieties suspected of causing DILI were related to the body’s state, the drugs themselves, and the medication environment. Conclusion Discovery of a series of TCM risk signals requires further confirmation of the risk and analysis of the causal mechanisms. References | Related Articles | Metrics

Select

Investigation of objectivity in the relationship between aristolochic acid and hepatocellular carcinoma FANG Zhie, LI Chengxian, BAI Zhaofang, ZHAO Xu, WANG Jiabo, XIAO Xiaohe 2024, 21(1): 20-24.  DOI: 10.19803/j.1672-8629.20230785 Abstract ( 161 )   PDF (812KB) ( 190 )   Objective To propose risk prevention and control strategies by sorting out Objective studies on hepatocellular carcinoma caused by aristolochic acid (AA). Methods The research progress of hepatocellular carcinoma caused by AA was briefly described. The scientific significance of the re-study of the correlation between AA and hepatocellular carcinoma was elucidated. The objectivity, authenticity, and systematic research content of the study on hepatocellular carcinoma caused by AA by our group were sorted out, and the prevention and control strategies of traditional Chinese medicines containing AA were proposed. Results and Conclusion The result clarified a lack of a correlation between AA and hepatocellular carcinoma. Risk prevention and control strategies for safe use of traditional Chinese medicines and preparations containing aristolochic acid were proposed including clarification of risk-benefit ratios, comprehensive analysis of pharmaceutical research data for regulatory decision-making; adoption of graded management measures for patients with different levels of risk; establishment of quality-control methods for safety and standards for limitations; and establishment of a new method for the scientific cognition and precise evaluation of the use of traditional Chinese medicines. References | Related Articles | Metrics

Select

Visual analysis of knowledge map of toxic Chinese medicine Changshan toxicity-effect transformation based the thought of “yin du wei neng” MA Li’na, HU Xiaozhen, ZHENG Changhui, SUN Ying, ZHAO Xu, CAO Junling, XIAO Xiaohe 2024, 21(1): 25-32.  DOI: 10.19803/j.1672-8629.20230778 Abstract ( 76 )   PDF (1699KB) ( 109 )   Objective Based on the idea of “yin du wei neng”, the knowledge map of Dichroa alkali and its derivatives were analyzed to provide theoretical basis for its toxicity-effect transformation.. Methods The relevant literature was retrieved from the core set of CNKICNKI database and Web of Science database from 1 January 1993 to 18 October 2023, and CiteSpace, VOSviewer and Excel software were used to analyze the publication volume, author, publishing agency, country, citation frequency and keywords of Chinese and English literature. Results A total of 235 articles were included, including 137 Chinese and 98 English articles. A total of 18 countries have conducted relevant studies on Ausomine and Authanone, among which the most studied country is China, followed by Israel, the United States and Japan. The institution with the largest number of articles in Chinese is the Key Laboratory of Veterinary Drug Creation of Lanzhou Institute of Animal Husbandry and Veterinary Medicine, Chinese Academy of Agricultural Sciences, with 11 articles, and the institution with the largest number of English articles is Volcani Institute of Agricultural Research with 17 articles. The top 10 cited Chinese and English literature mainly focuses on the pharmacological activity and synthesis of alcamine and acanthone. Conclusion The research on alcamine and its derivatives shows an upward trend, and the co-occurrence and clustering of Chinese and English keywords show that the pharmacological activity, toxicity and structural modification of alcamine and astillone are the current research hotspots. The in-depth study of Aytamine and its derived antimalarial mechanism, emetogenic mechanism and compatibility attenuation mechanism is the key research trend in the future. References | Supplementary Material | Related Articles | Metrics

Select

Research progress on the animal models of idiosyncratic drug-induced liver injury GAO Yuan, SHI Wei, XIAO Xiaohe, BAI Zhaofang, WANG Jiabo 2024, 21(1): 33-39.  DOI: 10.19803/j.1672-8629.20230802 Abstract ( 106 )   PDF (1281KB) ( 121 )   Objective To summarize the research on the animal models of IDILI, then to provide a scientific basis for guiding IDILI research and establishing its clinical risk prevention and control measures. Methods The research progress of IDILI model was discussed from various aspects, such as animal model, mathematical model and cellular model. Results and ConclusionIn recent years, IDILI has been gradually confirmed by researchers, and formed some hypothesis, such as Mitochondrial dysfunction hypothesis, Inflammatory stress hypothesis, immunological stress-mediated tri-elements synergetic mechanism hypothesis and genetic polymorphism hypothesis. Based on the characteristics of newly discovered “toxic” Chinese medicine-related IDILI, this team put forward the evaluation model and method of “disease-syndrome-based toxicology” of traditional Chinese medicine, on the basis of which it confirmed the problem of IDILI of Polygoni Multiflori Radix and other traditional Chinese medicines, and put forward the hypothesis of “toxicity due to three causes” mechanism of the immune stress of IDILI of traditional Chinese medicines, which better explained the characteristics of the pathogenesis of traditional Chinese medicines and the mechanism of IDILI. References | Related Articles | Metrics

Select

Screening and analysis of host factors interacting with NS1 proteins of influenza A virus based on the proteome chip ZHANG Yu, ZHANG Wei, GAO Shuangrong, CHEN Mengping, WANG Yaxin, XU Yingli, CAO Shan, ZHAO Ronghua, BAO Lei, LI Shuran, SUN Jing, BAO Yanyan, GENG Zihan, GUO Shanshan, JI Zuen, CUI Xiaolan 2024, 21(1): 40-44.  DOI: 10.19803/j.1672-8629.20230463 Abstract ( 82 )   PDF (2415KB) ( 69 )   Objective The human proteins interacting with influenza A virus (IAV) NS1 protein were obtained and analyzed to confirm the affected host biological processes and the core human proteins in the course of infection, providing thoughts for the development of drugs against influenza A virus. Methods NS1 sample and Biotin sample were hybridized with HuProt™ human proteome chip respectively, and the host protein bound to NS1 protein was screened on condition that both of repeated trials are matching Z-Score ≥ 3. The significantly specific proteins were further selected using a strict criteria (IMean_Ratio ≥ 1.4). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analysis were performed to evaluate these targets and MCODE was performed to explore the core proteins. Results A total of 195 significant specific proteins were obtained. Analysis results showed that these proteins were mainly involved in mRNA processing, RNA binding and protein binding, RNA degradation and amino acid biosynthesis. Among the four core proteins DDX6, HSPD1, PKLR and MTHFD1, DDX6 is related to RNA synthesis and translation. NS1 protein can promote viral infection by regulating IAV and host RNA, suggesting that DDX6 may be indispensable in this process. Although the other three proteins not clearly linked to influenza viruses, they can play a crucial role in the infection of other RNA viruses. Conclusion The human proteins bound to NS1 are mainly enriched in the process of RNA synthesis, processing, transcription, etc. The core proteins have potential to become new targets for anti-IAV, which need to be further verified by subsequent experiments. References | Related Articles | Metrics

Select

Effects of Shufeng Jiedu capsules prophylactic administration on TLR4-mediated inflammatory injury in lung tissue in a mouse model of inffuenza virus infeciton CAO Shan, PANG Bo, XU Yingli, ZHANG Jingsheng, CHEN Mengping, ZHANG Yu, WANG Yaxin, BAO Lei, GENG Zihan, GUO Shanshan, ZHAO Ronghua, CUI Xiaolan 2024, 21(1): 45-50.  DOI: 10.19803/j.1672-8629.20230419 Abstract ( 50 )   PDF (2190KB) ( 60 )   Objective To investigate the effects of prophylactic administration of Shufeng Jiedu capsules on mice withinfluenza A virus pneumonia and the possible mechanisms of intervention. Methods Influenza A (H1N1) virus (FM1 strain) was used to infect ICR mice with nasal drops to construct a viral pneumonia model. The general status of mice in each group was observed at a fixed time every day, and the lung index, inhibition rate, and viral load of mice in each group were calculated; Micro-CT and hematoxylin-eosin staining (HE) were used to observe histomorphological changes in mouse lungs; An enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) in lung tissues; protein immunoblotting (Western blot) was used to detect the expression levels of TLR4 and MyD88 proteins in lung tissues. Results Prophylactic administration of Shufeng Jiedu capsules reduced lung index, decreased viral load in lung tissue, repaired lung damage, attenuated lung lesions and decreased TNF-α and IL-6 levels in lung tissues in mice with influenza. Western blot results showed that Shufeng Jiedu capsules could down-regulatethe expression of TLR4 and MyD88 proteins in lung tissue. Conclusion Prophylactic administration of Shufeng Jieducapsules had a protective effect in mice with influenza A virus pneumonia. The mechanism is related to the inhibition of viral replication, improvement of lung tissue lesions, inhibition of inflammatory factor release and down-regulation of TLR4 and MyD88 protein expression in lung tissue. References | Related Articles | Metrics

Select

The mechanism of Sanhan Huashi Granules on pneumonia induced by human coronavirus 229E and OC43 in mice ZHANG Jingsheng, GAO Shuangrong, PANG Bo, LIU Lina, XU Yingli, CAO Shan, CHEN Mengping, ZHANG Yu, ZHAO Ronghua, CUI Xiaolan 2024, 21(1): 51-54.  DOI: 10.19803/j.1672-8629.20230400 Abstract ( 52 )   PDF (1772KB) ( 54 )   Objective To investigate the pharmacological effects of Sanhan Huashi Granules on mouse pneumonia caused by human coronavirus 229E or OC43, and to provide guidance for clinical application. Methods The experiment was divided into 2 batches, and each batch of experimental animals were randomly divided into 7 groups according to body weight: normal group, viral infection model group, chloroquine phosphate tablets group and Lianhua Qingwen granules group, respectively. The Sanhan Huashi mice were divided into three groups: high dose group (11 g·kg-1·d-1, equivalent to 52.8 g crude drug g·kg-1·d-1), medium-dose group (5.5 g·kg-1·d-1, equivalent to 26.4 g crude drug g·kg-1·d-1) and low-dose group (2.75 g·kg-1·d-1, equivalent to 13.2 g crude drug g·kg-1·d-1). The mice model of pneumonia induced by human coronavirus 229E or OC43 was used to evaluate the pharmacological effect of Sanhan Huashi granules on mice with coronavirus pneumonia by detecting lung index and lung pathological changes. Results The high-dose, medium-dose and low-dose groups of Sanhan Huashi granules can reduce the lung index and alleviate the pathological injury of lung tissue in mice. Conclusion Sanhan huashi Granules have therapeutic effect on mice pneumonia caused by human coronavirus 229E or OC43 infection. References | Related Articles | Metrics

Select

Discussion on traditional Chinese medicine theory and modern pharmacology of Xuanfei Baidu decoction for treating novel coronavirus infection ZHANG Jingsheng, JI Zuen, PANG Bo, XU Yingli, CAO Shan, ZHANG Yu, SUN Qiyue, SUN Jing, LI Shuran, ZHANG Wei, ZHAO Ronghua, CUI Xiaolan 2024, 21(1): 55-58.  DOI: 10.19803/j.1672-8629.20230620 Abstract ( 57 )   PDF (1232KB) ( 68 )   Objective To discuss the traditional Chinese medicine (TCM) theory of Xuanfei Baidu decoction in treating novel coronavirus infection, summarize the experimental study of this prescription, and provide reference for later clinical and experimental purposes. Methods Using the methods of theoretical research and literature investigation, this paper discusses and summarizes the TCM theory of Xuanfei Baidu decoction and summarizes the experimental study. Results Xuanfei Baidu decoction is suitable for patients with dampness-toxic stagnation of lung. And the PD-1/IL17A, IL-6/STAT3 and CXCL2/CXCR2 pathways were used to ameliorate lung injury and NF-κB pathway to alleviate intestinal diseases. Conclusion Xuanfei Baidu decoction is a combination of TCM and science and technology, which is supported by both TCM theory and modern experimental research evidence. References | Related Articles | Metrics

Select

Research status of cognitive dysfunction after SARS-CoV-2 infection LI Shuran, GUO Shanshan, JI Zuen, ZHANG Wei, CUI Xiaolan 2024, 21(1): 59-64.  DOI: 10.19803/j.1672-8629.20230695 Abstract ( 132 )   PDF (1358KB) ( 130 )   Objective To review the relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and cognitive dysfunction and the mechanism of cognitive dysfunction in post-COVID-19 syndrome. Methods CNKI and PubMed databases were searched to collect relevant research reports on cognitive dysfunction after SARS-CoV-2 infection by traditional Chinese medicine (TCM) and western medicine from January 1, 2020 to October 30, 2023. Results Cognitive dysfunction might occur after SARS-CoV-2 infection, which might be related to the neuroaggressive, neurotropic, and neurovirulent nature of the SARS-CoV-2 virus, or to factors such as post-infection-mediated hyperinflammation, serotonin levels, and viral metastasis. It was also found that some TCM monomers had the effect of improving cognitive dysfunction after SARS-CoV-2 infection. Conclusion Cognitive dysfunction may occur for a short time or for a long time after SARS-CoV-2 infection, and its mechanism needs to be further verified by clinical and basic research. References | Related Articles | Metrics

Select

The inhibitory effect and mechanism of Celastrol on adipogenic differentiation in 3T3-L1 YUE Lanxin, SHEN Pan, ZHOU Lei, HUANG Congshu, ZHOU Wei, GAO Yue 2024, 21(1): 65-73.  DOI: 10.19803/j.1672-8629.20230708 Abstract ( 46 )   PDF (3831KB) ( 69 )   Objective To study the inhibitory effect and mechanism of Celastrol (Cela) on adipogenic differentiation in preadipocytes (3T3-L1). Methods CCK-8 was used to determine the optimal concentration of Cela for 3T3-L1 cells. Oil red O staining and immunofluorescence (Perilipin1, Adiponectin) were used to imply the inhibitory effect of Celastrol on 3T3-L1 adipogenic differentiation at different stages. Western Blot (WB) was used to detect proteins expression related to lipid metabolism and differentiation in 3T3-L1 cells treated with different concentrations of Cela; WB, microRNA (miRNA) sequencing and qPCR were used to analyze undifferentiated (Con), differentiation Day1 (MDI), 250 nmol·L-1Cela treatment on the first day of differentiation (MCT), and KEGG and GO enrichment analysis were performed; mmu-miR-5121 mimics and inhibitor were overexpressed, then changes in related proteins were detected by WB, and differentiation results were detected by oil red O staining. Results The optimal concentrations of celastrol for treatment of 3T3-L1 cells were 250 nmol·L-1and 500 nmol·L-1. Oil red O staining and immunofluorescence results showed that 250 nmol·L-1Cela significantly inhibited the adipogenic differentiation of 3T3-L1, 250 nmol·L-1Cela at the early stage (the first day) significantly inhibited the adipogenic differentiation of 3T3-L1. WB results showed that treatment with 250 nmol·L-1celastrol significantly inhibited the protein expression of DFCP1, FAS, ACC, and PPARγ in 3T3-L1 cells. On the first day of differentiation, the expression of FAS and ACC increased. After treatment with 250 nmol·L-1Cela, the expression of ACC and FAS protein significantly decreased; miRNA sequencing screening and validation showed that mmu-miR-5121 decreased on the first day of differentiation, but increased after Cela treatment. Transfecting 5121 inhibitor increased the content of FAS and ACC, while 5121 mimics showed the opposite effect. Transfecting 5121 inhibitor alone led to adipogenic differentiation, while 5121 mimics could effectively inhibit normal differentiation. And 250 nmol·L-1Cela can inhibit differentiation induced by 5121 inhibitor. Conclusion 250 nmol·L-1Cela significantly inhibited the differentiation at early state of 3T3-L1 adipogenic differentiation, possibly by upregulating the content of mmu-miR-5121 and inhibiting the expression of FAS and ACC. References | Related Articles | Metrics

Select

Hepatotoxic components in Psoraleae Fructus based on high-content screening technology SHANG Huiying, WEI Xue, CHENG Hongbo, MA Zengchun, TU Bodan, XIAO Chengrong, LIU Xian, GAO Yue 2024, 21(1): 74-82.  DOI: 10.19803/j.1672-8629.20230656 Abstract ( 67 )   PDF (3502KB) ( 75 )   Objective To screen the potential hepatotoxic components in Psoraleae Fructus and explore the possible mechanisms using high-content screening technology. Methods The IC50 values of ten components in Psoraleae Fructus, including isobavachin, bavachinin, bavachin, isobavachalcone, 4’-O-methyl- bavachalcone, corylin, psoralen, ispsoralen, psoralidin, and bakuchiol were determined by CCK-8 cell viability assays. After treating HepG 2 cells with the same concentration of individual drug for 24 h, high-content screening was performed. The potential hepatotoxic components were revealed by evaluating the average fluorescence intensity of positive cells of four indicators, including reactive oxygen species, reduced glutathione, mitochondrial membrane potential and mitochondrial superoxide. Results CCK-8 cell viability assays showed that the IC50 values of isobavachin, bavachinin, bavachin, isobavachalcone, 4’-O-methyl-bavachalcone, corylin, ispsoralen, psoralidin, and bakuchiol were 52.69, 42.72, 83.63, 42.29, 57.43, 110.80, 1 420.00, 23.58 and 25.34 μmol·L-1, respectively. The high-content screening analysis showed that bavachinin, bavachin, isobavachalcone, psoralidin and bakuchiol could significantly increase the level of reactive oxygen species at the same concentration of 20 μmol·L-1; Isobavachalcone, 4’-O-methyl-bavachalcone, corylin, ispsoralen, psoralidin, bakuchiol can lead to a protective increase in the level of reduced glutathione; Additionally, isobavachalcone, psoralidin and bakuchiol could prominently decrease the level of mitochondrial membrane potential and promoted the accumulation of mitochondrial superoxide. Conclusion Isobavachalcone, psoralidin and bakuchiol were the main mitotoxic components in Psoraleae Fructus, which promoted Psoraleae Fructus-induced liver injuries. The specific mechanisms of the three components remains to be investigated in the future. References | Related Articles | Metrics

Select

Protective effect and mechanism of dimethyl fumarate against intestinal radiation injury ZHANG Liangliang, HU Changkun, WU Zekun, ZHOU Wei, LIAO Zebin, GAO Yue 2024, 21(1): 83-88.  DOI: 10.19803/j.1672-8629.20230671 Abstract ( 63 )   PDF (2410KB) ( 69 )   Objective To investigate the protective effect of dimethyl fumarate (DMF) on irradiation (IR)-induced intestinal damage and the underlying mechanism. Methods 60Co γ ray irradiator was used to induce radiation injury in mice. Small intestines were collected after irradiation and subjected to H&E and TUNEL staining to detect the pathological changes and apoptosis in situ. Inflammatory response was determined by quantifying levels of interleukin-1β (IL-1β), interleukin-6(IL-6), interleukin-18(IL-18), tumor necrosis factor-α(TNF-α), NOD-like receptor protein 3(NLRP3) or melanoma deficiency factor 2 (AIM2) in intestine with enzyme-linked immunosorbent assay. Western blot and immunofluorescence staining were used to detect the expression of NLRP3 and AIM2 in small intestine. To verify the essential role of NLRP3 and AIM3 on radio-protective of DMF on small intestine, the selective agonists were employed. Results DMF (15 mg·kg-1) significantly improved the pathological status of small intestine and decreased the apoptosis level of intestinal cells upon whole body IR exposure. DMF could also significantly inhibit the inflammatory response on small intestine induced IR injury. Western blot results and tissue immunofluorescence staining showed that DMF could significantly suppress the upregulation of NLRP3 and AIM2. With selective agonists, the radio-protective effect of DMF on small intestine was diminished, indicating the critical role of NLRP3 and AIM2 inflammasome signaling involved in the anti-radiation activity of DMF. Conclusion DMF is a promising agent to alleviate IR-induced intestinal injury, and the inhibition of NLRP3/AIM2 inflammasome signaling seem to be the underlying mechanism involved in the radio-protective effect of DMF. References | Related Articles | Metrics

Select

Determination of sialic acid in recombinant human follicle stimulating hormone by high performance liquid chromatography with DMB derivatization WANG Lyuyin, LI Yi, SUN Yue, HU Xinyue, ZHANG Hui, LI Jing, LIANG Chenggang 2024, 21(1): 89-93.  DOI: 10.19803/j.1672-8629.20230498 Abstract ( 66 )   PDF (1408KB) ( 66 )   Objective To develop a 4,5-methylenedioxy-1,2-phenylenediamine dihydrochloride (DMB) derivatization method based on high-performance liquid chromatography-fluorescence detector (HPLC-FLD)(DMB derivatization method) that can concurrently quantify both N-glycolylneuraminic acid (Neu5Gc) and N-acetylneuraminic acid (Neu5Ac) in rhFSH. Methods A comparative study was undertaken between the o-phenylenediamine derivatization method based on high-performance liquid chromatography(o-phenylenediamine derivatization method) and DMB derivatization method. The optimized DMB derivatization method with refined hydrolysis conditions was established and demonstrated as follows: The rhFSH solution was first subjected to acid hydrolysis, followed by derivatization with DMB. The resulting solution was then separated using an Agilent ZORBAX 300SB-C18 chromatographic column (250 mm×4.6 mm, 5 μm) and analyzed by a fluorescence detector. Results When compared to the o-phenylenediamine derivatization, the optimized DMB derivatization method proves to be more effective in separating Neu5Gc and Neu5Ac related impurities. The optimized DMB derivatization method showcases superior specificity, with both Neu5Gc and Neu5Ac demonstrating a strong linear relationship with peak area within the concentration ranges of 0.5~5.0 μg·mL-1(r=0.999 9) and 25~250 μg·mL-1 (r=0.999 8). The limit of detection and quantification (LOD and LOQ) for Neu5Gc are impressively low as 11.07 ng·mL-1and 33.21 ng·mL-1 respectively, comparable to the levels of Neu5Ac (LOD: 10.30 ng·mL-1, LOQ: 20.60 ng·mL-1). Besides, the recovery rates for Neu5Gc and Neu5Ac are (99.63±1.33)% (n=9) and (100.62±1.58)% (n=9), with low RSDs of 1.3% (n=9) and 1.5% (n=9), respectively. Conclusion The method demonstrates commendable specificity, exceptional sensitivity, and noteworthy precision and accuracy, which would be ideally suited for the precise quantification of Neu5Gc and Neu5Ac content in rhFSH. References | Related Articles | Metrics

Select

Considerations for revision of safety information in package inserts of anti-cancer drugs in post-market phase XIONG Weiyi, REN Jingtian 2024, 21(1): 94-97.  DOI: 10.19803/j.1672-8629.20230609 Abstract ( 201 )   PDF (1187KB) ( 295 )   Objective To outline the considerations for the revision of safety information in package inserts of anti-cancer drugs in the post-market phase so as to provide reference for marketing authorization holders (MAH). Methods Based on the revision accomplished by the Center for Drug Reevaluation (CDR) of the National Medicinal Products Administration, the purpose, reasons, evidence and principles related to revision were presented. Results and Conclusion The revision of safety information in package inserts of drugs is a multi-departmental project. CDR will continue to improve the safety information for all authorized drugs in China, including anti-cancer drugs. MAH should fulfill their responsibility to improve drug package inserts in time so as to ensure the safe use of drugs. References | Related Articles | Metrics

Select

Updates and reflections on expedited reporting of safety information during drug clinical trials LIU Min, CHEN Yan, LIU Wendong, WANG Haixue 2024, 21(1): 98-101.  DOI: 10.19803/j.1672-8629.20230624 Abstract ( 331 )   PDF (1324KB) ( 469 )   Objective To advance our understanding of the requirements on implementation of expedited reporting of safety information. Methods The background and changes of FAQ 2.0, including the scope, time limit, and method of expedited reporting, were interpreted and analyzed. Results and Conclusion In order to improve the quality of safety information reports, the applicant, as the main responsible person, should fulfil his responsibility, communicate willingly with all the parties involved in the clinical trial, and collect as much information as possible. The drug regulatory authority should continue to elevate the level of pharmacovigilance during the clinical trial, improve the system of standards and codes for practice, enhance the ability to assess risks, and upgrade informatization so as to protect the safety, rights and interests of the subjects. References | Related Articles | Metrics

Select

Adverse drug reaction among 694 patients in an epilepsy physician-pharmacist joint clinic JIANG Wenshuo, YANG Li 2024, 21(1): 102-106.  DOI: 10.19803/j.1672-8629.20230443 Abstract ( 152 )   PDF (1418KB) ( 188 )   Objective To analyze the incidence,dominating types and related factors of adverse drug reaction (ADR) in patients at an epilepsy physician-pharmacist joint clinic and to provide evidence for individualized treatment of epilepsy. Methods A retrospective survey was conducted among patients who visited the epilepsy physician-pharmacist joint clinic in our hospital in 2020-2021. The gender and age of these patients and incidence of adverse reactions were statistically analyzed before Chi-square tests were performed on the correlations between the incidence of ADR and gender, age and combined medications. Results The incidence of ADR averaged 36.17% (251/694), which was 37.08% among male patients (142/383) and 35.05% among female ones (109/311), so the difference was of no statistical difference (χ 2=0.306, P=0.580). The incidence of ADR was 24.00%, 33.88%, 42.96%, and 55.10% respectively in the group aged 14 or older, in the group ages 15 to 44, in the group aged 45-64 and in the group aged 65 and older, so the difference was statistically significant (χ 2=16.226, P=0.001). The incidence of ADR in patients treated with combinations of drugs and those without was 45.00% and 26.65%, respectively, and the difference was of statistical significance (χ 2=25.279, P=0.000). Conclusion Medications for epilepsy should be individualized based on the gender, age, and combination of drugs. Patients or their family members should be reminded of the importance of regular re-examination to ensure the safety of medication. References | Related Articles | Metrics

Select

Safety of nirmatrelvir/ritonavir in the treatment of novel coronavirus infections CHEN Huayan, JIANG Dongbo, GUO Chunlian, YANG Jiaqi, LI Yuxin, CAI Weiming 2024, 21(1): 107-110.  DOI: 10.19803/j.1672-8629.20230207 Abstract ( 126 )   PDF (1248KB) ( 140 )   Objective To investigate the safety of nirmatrelvir/ritonavir in the treatment of novel coronavirus infections (COVID-19), and to provide reference for clinical use. Methods The medical records of adult patients infected with COVID-19 who were admitted to the Affiliated Hospital of Guangdong Medical University between December 15, 2022 and February 15, 2023 and treated with Paxlovid were retrospectively investigated via the electronic medical record system. The data on adverse reactions related to paxlovid, including the time of occurrence, clinical manifestations, severity, management and outcomes was analyzed before the clinical characteristics of patients with and without adverse reactions were compared. Results A total of 326 patients were enrolled, including 225 males (69.02%) and 101 females (30.98%). Fifty-six adverse drug reactions occurred in 55 patients, so the incidence was 16.87%, including 28 cases of digestive system injury, 17 cases of liver dysfunction, 4 cases of nervous system injury, 3 cases of respiratory system injury, and 3 other cases. Among them, one patient experienced both respiratory and digestive system injury. There were 18 cases (32.73%) of grade 1, 37 cases (67.27%) of grade 2, and no serious (grade ≥3) adverse drug reactions according to the grading of severity. The clinical outcomes were generally good after drug withdrawal/reduction and symptomatic treatment. Twenty-eight of these cases (50.91%) were cured, 24 cases (43.64%) improved, and 3 cases (5.45%) were out of contact. There was no statistically significant difference in the clinical characteristics (gender, age, and various comorbidities) between patients with and without adverse reactions (P>0.05). Conclusion Paxlovid is safe in the treatment of COVID-19, with mild symptoms of adverse reactions manifested as diarrhea and liver function abnormalities, and is well tolerated by patients. References | Related Articles | Metrics

Select

Recent research of antiviral drugs and vaccines for Mpox GAO Xu, PENG Jin’e, LI Xingwang, ZHANG Wei 2024, 21(1): 111-116.  DOI: 10.19803/j.1672-8629.20230690 Abstract ( 106 )   PDF (1330KB) ( 86 )   Monkeypox (Mpox) is a disease caused by infection with the monkeypox virus (MPXV). There is no specific therapeutic drug for monkeypox virus in the world, and antiviral drugs and vaccines are primarily used for the treatment and prevention of smallpox and other orthopoxviral diseases. The antiviral drugs mainly include Teicovirimat, Cidofovir, Brincidofovir, while vaccines mainly use ACAM2000, MVA-BN, and LC16, which have shown effectiveness in treating and preventing Mpox. Currently, Given the absence of a specific drug and a more effective and safer vaccine, these drugs and vaccines can be used in early treatment and prevention to alleviate clinical symptoms caused by the monkeypox virus, reducing the rate of severe disease and mortality. The thesis was discussed in terms of antiviral drugs and vaccines mechanism of action, clinical trials and safety to study the antiviral drugs and vaccines currently used internationally for the treatment of Mpox, with a view to providing reference for the treatment and prevention of Mpox in China. References | Related Articles | Metrics

Select

Assessment of drug-induced liver injury via nR modified Hy’s law and PALT BUCHANAN James 2024, 21(1): 117-120.  DOI: 10.19803/j.1672-8629.20230615 Abstract ( 100 )   PDF (1385KB) ( 124 )   Hepatotoxicity associated with drugs, herbal medications and other complementary or alternative therapies has been a global concern for safety professionals and regulatory authorities. Instant identification of liver injury remains a challenge during both clinical development and in the post-marketing period. Advances have been made in the criteria used to identify cases of hepatotoxicity that are most likely to progress to liver failure or death. In addition, new methods are available to estimate the magnitude of hepatocyte loss associated with liver injury. This paper reviews these new methodologies and their applications to the ongoing monitoring and evaluation of product-related hepatoxicity. References | Related Articles | Metrics