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15 January 2023, Volume 20 Issue 1 Previous Issue    Next Issue

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Development and clinical safety of paediatric medicines in China JIANG Jiandong 2023, 20(1): 1-6.  DOI: 10.19803/j.1672-8629.20220720 Abstract ( 292 )   PDF (1302KB) ( 300 )   Objective To explore the priorities of development of paediatric medicines in China and give advice on the safety of paediatric drugs in clinical use. Methods By analyzing the guidelines, regulations and related literature on development of paediatric medicines and clinical use at home and abroad in recent years, the status quo of and problems with development of paediatric medicines in China were presented, and the factors influencing the safety of clinical use of paediatric medicines were clarified. Results and Conclusion In view of the challenges to paediatric medicines and with reference to related experience, this paper outlines the prospect of the research and development of paediatric medicines and clinical drug safety in China, and puts forward corresponding countermeasures and suggestions. References | Related Articles | Metrics

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Research progress in oncolytic drugs ZHOU Pengbo, ZHOU Xiaobing, HUANG Ying, GENG Xingchao 2023, 20(1): 7-11.  DOI: 10.19803/j.1672-8629.20220222 Abstract ( 113 )   PDF (1191KB) ( 177 )   Objective To find out more about the oncolytic virus and related drugs so as to provide reference for subsequent safety evaluation of oncolytic drugs. Methods The research progress in the mechanism of oncolytic virus, clinical research of related drugs and their combination therapy in recent years were summarized and analyzed. Results There were four oncolytic viral drugs on the market, all of which had good curative effects. With the development of biotechnology, preparation strategies of oncolytic virus became more diverse and effective. Conclusion Oncolytic viral therapy has many advantages, such as high killing efficiency, good targeting, low adverse reactions, multiple ways to kill tumors, little drug resistance and low cost. It is expected to become a new tumor treatment strategy. References | Related Articles | Metrics

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Biodistribution of oncolytic virus HSV-1 expressing human PD-1 antibody in cynomolgus macaques WANG Xin, SUN Li, WANG Chao, LI Lulu, WANG Sanlong, LIU Jiajia, TIAN Chao, LI Xiaopeng, GENG Xingchao 2023, 20(1): 12-18.  DOI: 10.19803/j.1672-8629.20220181 Abstract ( 84 )   PDF (1482KB) ( 67 )   Objective To establish a real-time quantitative PCR (qPCR) analysis method to investigate the biodistribution of oncolytic virus product HSV-1/hPD-1 in mice and cynomolgus macaques, and to detect samples collected during the concomitant biodistribution (shedding included) study in the process of investigating the repeat-dose toxicity in cynomolgus macaques. Methods According to the specific genetic sequences of drugs, primers and probes were designed and a proper PCR reaction system was established. Standard curves for detection were constructed and verified methodologically. Tissues and organs collected during repeat-dose toxicity experiments, including blood, gonads, kidneys, livers, lungs, hearts, brains, spleens, lymph nodes (mesenteric and inguinal), injection sites (skeletal muscle),tear gland, salivary gland, dorsal root ganglion, urine and feces, were subjected to qPCR detection. Results A universal standard curve named pMD18T-1093 was constructed, which could be used to quantitatively determine the copy number of the tested drugs in different tissues of mice and cynomolgus macaques. The tested drugs predominately remained at the injection sites and were sparsely distributed to the lung and brain before being cleared away by urine. Drug distribution was not detected in any other tissues of cynomolgus macaques. The amount of drugs located in target organs increased in a dose-dependent manner and decreased gradually with time rather than being accumulated in the body. Drugs detected in the brain might have been due to sample pollution. Conclusion A qPCR analysis method for preclinical biodistribution studies has been established in the study, which is expected to facilitate future studies on biodistribution of other drugs for gene therapy. References | Related Articles | Metrics

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Toxicity of gene therapy drug AAV5-LPLS447X in mice HOU Tiantian, MA Sisi, WU Xiaobing, HUO Guitao, PAN Dongsheng, WANG Chao, XIA Yan, LIU Yi, ZHOU Xiaobing, LIU Guoqing, GENG Xingchao 2023, 20(1): 19-26.  DOI: 10.19803/j.1672-8629.20220338 Abstract ( 82 )   PDF (1562KB) ( 49 )   Objective To assess the toxicity of gene therapy drug AAV5-LPLS447X (GC304) in mice. Methods ①Acute toxicity study:40 C57BL/6N mice were randomly divided into 2 groups: the vehicle group and the test substance group. After a single tail vein injection, clinical symptoms, body weight and food intake were measured for 15 consecutive days, and necropsy was performed on the 15th day.② Long-term toxicity study: 440 mice were randomly divided into 4 groups: the vehicle group, low-dose group(1×1013 vg·kg-1), middle-dose group(5×1013 vg·kg-1) and high-dose group(1.5×1014 vg·kg-1). After a single tail vein injection, such indicators of toxicity as body weight, food intake, hematology, serum biochemistry, immunotoxicity and immunogenicity were measured. The mice were dissected at 4 weeks and 6 months after administration before being examined histopathologically. The distribution and expression of GC304 in various organs of the animals were detected by qPCR at 2 weeks, 4 weeks, 3 months, and 6 months. Results ①In the acute toxicity study: the clinical symptoms, body weight and food intake of the animals were normal, and no gross pathological changes related to GC304 were found.② In the long-term toxicity study: no obvious abnormalities related to GC304 were found in clinical symptoms, body weight, food intake, cytokines or T lymphocyte subsets. GC304 reduced plasma triglycerides and the albumin/globulin ratio associated with anti-drug antibodies, and induced the production of anti-AAV5-binding antibodies and neutralizing antibodies, which persisted up to 6 months after administration. After administration of GC304, no anti-LPL antibodies were detected. Histopathological results showed that drug-related inflammatory cell infiltration occurred at the injection site 4 weeks after administration in mice, and recovery was seen 6 months after administration. Drug-related changes were an active germinal center in the spleen with increased predisposition macrophages, and an active germinal center in the inguinal lymph nodes with increased predisposed macrophages. The results of qPCR showed that GC304 was widely distributed and expressed in the peripheral blood and organs of mice, especially in the liver. Conclusion After a single intravenous administration in C57BL/6N mice, GC304 is mainly expressed and distributed in the liver, and the animals are well tolerated without obvious toxic reactions, which provides reference for clinical trials of the drug. References | Related Articles | Metrics

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Toxicity of gene therapy drug AAV5-LPLS447X (GC304) in cynomolgus monkeys HOU Tiantian, XIA Yan, PAN Dongsheng, HUO Guitao, MA Xuemei, LIU Ziyang, SUN Li, LIU Yi, YAN Jian'ao, WU Xiaobing, ZHOU Xiaobing, LIU Guoqing, GENG Xingchao 2023, 20(1): 27-33.  DOI: 10.19803/j.1672-8629.20220341 Abstract ( 91 )   PDF (1440KB) ( 63 )   Objective To determine the toxicity of gene therapy drug AAV5-LPLS447X (GC304) in cynomolgus monkeys. Methods Thirty cynomolgus monkeys were divided into the vehicle control group, low-dose group and high-dose group before being injected with vehicle, 3×1013 vg·kg-1 and 1×1014 vg·kg-1 GC304 respectively. During the study, All animals had their clinical symptoms and injection sites observed while food consumption and body weight were measured weekly. Immunogenicity tests (involving anti-AAV5-binding antibodies, anti-AAV5-neutralizing antibodies, and anti-LPL-binding antibodies), hematology, clinical chemistry, coagulation parameters and urinalysis were performed at different time points before and after administration, while T lymphocyte typing and cytokines, ECG, blood pressure, body temperature and ophthalmology were observed. At 4 weeks and 6 months after administration, cynomolgus monkeys were dissected for gross observation, organ weight and histopathological examination. At the same time, biodistribution of GC304 was studied and expression products were determination, and the target gene DNA in blood was detected at different time points. Results The clinical symptoms, injection sites, body weight, food consumption, eye indexes, body temperature, blood pressure, electrocardiogram, blood coagulation, clinical chemistry, T lymphocyte typing, urine, cytokines and organ weight were normal. Platelets in the high-dose group decreased 4 weeks after administration. Histopathological changes associated with the test article were active germinal centers in the spleen and inguinal lymph nodes with increased chromosomal macrophages. Both a low dose and a high dose caused cynomolgus monkeys to produce anti-AAV5 binding and anti-AAV5 neutralizing antibodies, and the two antibodies remained at high levels 6 months after administration, but there was no obvious “dose-effect” relationship. Anti-LPL antibody production in cynomolgus monkeys was not significantly induced after administration of GC304. The results of qPCR detection showed that the test article was widely distributed and expressed in the peripheral blood and organs of cynomolgus monkeys, but concentrated in the liver. Conclusion Cynomolgus monkeys can be singly dosed with GC304 via intravenous injection, which is well tolerated without obvious toxic reactions, and GC304 is mainly distributed and expressed in the liver, which can provide data for subsequent clinical trials. References | Related Articles | Metrics

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Nonclinical evaluation of safety of gene therapy drug AAV5 lipoprotein lipase variant (GC304) in the nervous system LI Qianqian, XIA Yan, HOU Tiantian, WANG Chao, SHI Xixi, MA Xuemei, LIU Ziyang, ZHANG Yingli, WU Xiaobing, WANG Sanlong, LIU Guoqing, GENG Xingchao 2023, 20(1): 34-39.  DOI: 10.19803/j.1672-8629.20220587 Abstract ( 102 )   PDF (1389KB) ( 126 )   Objective To determine the safety of GC304 in humans by focusing on evaluation of the effect of GC304 on the central nervous system of C57BL/6N mice. Methods A total of 40 mice, half male and half female, were given vehicle control and 1.0×1013, 5×1013, 1.5×1014 vg·kg-1 GC304 through the caudal vein respectively using the function observational battery (FOB) test method. The motor function, sensory function, autonomous activity and other behaviors of mice were observed before administration and 1 h, 4 h, 24 h, 48 h, 96 h, 7 d and 14 d after administration respectively. In addition, levels of TG, TP and ALB were detected 14 days after administration. Results The results of fluorescent quantitative PCR used in the early stage of this study showed that the copy number of the target genes could still be detected in the brain region two weeks after 1.5 ×1014 vg·kg-1 GC304 was given. Based on the above data, the behavioral study of GC304 was carried out. The results showed that after administration of GC304, triglycerides related to pharmacological effects could be significantly reduced. No obvious abnormalities were found during cage observation, hand-held observation, open field observation and reflex evaluation of animals in any of the dose groups of GC304 two weeks after administration. Conclusion GC304 can be directed into the brain region and a small number of target genes are still distributed in the brain region 14 days after administration, but GC304 will not induce neurotoxicity. References | Related Articles | Metrics

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Establishment and evaluation of a mouse model combining disease with syndrome of HCoV-229E pneumonia with lung-attacking damp-heat syndrome PANG Bo, ZHANG Jingsheng, GUO Shanshan, SUN Jing, BAO Lei, XU Yingli, CAO Shan, CHEN Mengping, WANG Yaxin, ZHAO Ronghua, CUI Xiaolan 2023, 20(1): 40-45.  DOI: 10.19803/j.1672-8629.20220320 Abstract ( 60 )   PDF (2362KB) ( 63 )   Objective To establish a disease-syndrome pneumonia mouse model of lung-attacking damp-heat virus caused by external damp-heat stimulation and human coronavirus HCoV-229E virus infection. Methods The animal model of damp-heat epidemic was evaluated in terms of TCM syndrome, lung indexes and viral loads, pathological structure and imaging of the lung, the contents of serum gastrin (Gas), prostaglandin E2 (PGE2), cyclic adenosine monophosphate (cAMP) in the hypothalamus and muscle glycogen of mice infected with damp-heat virus for different days. Results This mouse model showed that the mice’s diet decreased while water consumption increased, and that their fur became dull and yellow, movements sluggish, and stool loose. The lung index increased (P < 0.01), the viral nucleic acid in the lung was positively expressed, and pathological changes and speckled shadows were observed in the lung tissue. The contents of muscle glycogen, serum gastrin, hypothalamic cAMP and prostaglandin E2 in mice increased significantly after infection (P < 0.05). Conclusion The mouse model of HCoV-229E and damp-heat stimulation established in this study is consistent with clinical symptoms, which can serve as a reliable animal evaluation model for emergency screening or research of drugs for treating viral pneumonia with this syndrome. References | Related Articles | Metrics

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Pharmacological effects of Jinzhen oral liquid against viral pneumonia in mice infected with influenza H1N1/FM1 and parainfluenza virus ZHANG Jingsheng, GAO Shuangrong, PANG Bo, BAO Lei, SUN Jing, CHEN Mengping, XU Yingli, CAO Shan, GUO Shanshan, ZHAO Ronghua, CUI Xiaolan 2023, 20(1): 46-51.  DOI: 10.19803/j.1672-8629.20220303 Abstract ( 108 )   PDF (2138KB) ( 125 )   Objective To evaluate the effect of Jinzhen oral liquid (JOL) on a mouse model of pneumonia induced by influenza ( H1N1) FM1 strain and parainfluenza virus in order to provide reference for clinical applications. Methods Mice were randomly divided into the normal group, model group, JOL high-dose group ( 8 g· kg-1·d-1), JOL medium-dose group ( 4 g·kg-1·d-1 ), and JOL low-dose group ( 2 g·kg-1·d-1 ). Mice were infected via intranasal infection with influenza H1N1/FM1 or parainfluenza virus. Oseltamivir phosphate granules, ribavirin granules and Resuqing oral liquid were used as positive control drugs. Four days after the infection,the lung indexes,inhibition rate, pathological changes were observed．In the death protection experiment,the death rate within 14 days was analyzed．Results Compared with the model group, treatment with JOL could lower the lung indexes, alleviate pathological changes of the lung,and reduce mortality of mice. Conclusion JOL can effectively protect the mouse model from pneumonia induced by influenza H1N1/FM1 or parainfluenza virus. References | Related Articles | Metrics

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Effects of Shufeng Jiedu capsules combined with levofloxacin in the treatment of mouse pneumonia infected by multidrug-resistant Pseudomonas aeruginosa SUN Jing, ZHAO Ronghua, BAO Lei, GUO Shanshan, GENG Zihan, LI Shuran, XU Yingli, CUI Xiaolan 2023, 20(1): 52-56.  DOI: 10.19803/j.1672-8629.20220289 Abstract ( 128 )   PDF (1877KB) ( 78 )   Objective To clarify the pharmacological effect of Shufeng Jiedu capsules combined with levofloxacin on a multidrug-resistant Pseudomonas aeruginosa infection-induced pneumonia model and death model in mice, and provide data for clinical applications. Methods Experimental animals were randomly divided into six groups according to their body weight: the normal control group, model control group, levofloxacin alone group, and combined-administration groups at three doses (2.08, 1.04, 0.52 g-1·kg-1·d-1) of Shufeng Jiedu capsules combined with levofloxacin. Pneumonia and death models in mice were established via intranasal infection with multidrug-resistant Pseudomonas aeruginosa. Then, the lung indexes, inhibition rate of these indexes, pathological changes of lung tissue, contents of IL-6 and TNF-α in lung tissue, mice mortality, average survival, and life extension rates were detected. Results The three-dose groups of Shufeng Jiedu capsules combined with levofloxacin could significantly reduce the lung indexes, mitigate pathological injury to lung tissue, lower the levels of IL-6 and TNF-α production as well as the mortality of mice, and prolong the average survival. Conclusion The combined administration of Shufeng Jiedu capsules and levofloxacin has a significantly better effect on the mice model of pneumonia and death caused by multidrug-resistant Pseudomonas aeruginosa infection compared with the levofloxacin alone group. References | Related Articles | Metrics

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Research progress in traditional Chinese medicines against multidrug-resistant Pseudomonas aeruginosa pneumonia XU Yingli, PANG Bo, CAO Shan, CHEN Mengping, SUN Jing, ZHAO Ronghua, ZHANG Jingsheng, ZHOU Lirun, WANG Yaxin, CUI Xiaolan 2023, 20(1): 57-60.  DOI: 10.19803/j.1672-8629.20220328 Abstract ( 84 )   PDF (1205KB) ( 71 )   Objective To study the research progress in traditional Chinese medicines against multidrug-resistant Pseudomonas aeruginosa pneumonia and to provide reference for prevention and treatment of Pseudomonas aeruginosa pneumonia infections. Methods Domestic and foreign literature was consulted. The role of TCMs in regulation of bacterial drug resistance, the quorum sensing system, and host microenvironments was reviewed. Results Compared with antibiotics that directly target bacteria, traditional Chinese medicines were characterized by extensive sources, multiple components, multiple targets, and less resistance to drugs, which was of great value for treating multidrug-resistant Pseudomonas aeruginosa pneumonia. Traditional Chinese medicines can play a role in treating anti-bacterial pneumonia by inhibiting the expressions of inactivated enzymes, inhibiting bacterial efflux, regulating the quorum sensing system, improving the host innate immune barrier, and regulating the immune microenvironment. Conclusion It is of great significance to explore the treasure house of TCMs and develop new drugs that are effective against multidrug-resistant Pseudomonas aeruginosa pneumonia in the future. References | Related Articles | Metrics

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Scoping review of near real-time surveillance of vaccine safety SUN Yixin, LIU Zhike, ZHAN Siyan 2023, 20(1): 61-67.  DOI: 10.19803/j.1672-8629.20220619 Abstract ( 209 )   PDF (1414KB) ( 214 )   Objective To review the characteristics, processes and mechanisms of current near real-time surveillance systems for vaccine afety worldwide, and to establish a standardized workflow. Methods The scoping review was used to evaluate, define, retrieve and screen information related to the near real-time surveillance systems of vaccine safety. The framework synthesis was applied to determine the analytical framework, coding and mapping information about characteristics of data, surveillance procedures and operational mechanisms before the core elements of near real-time surveillance were summarized and a standardized workflow was established. Results Fifty pieces of literature were included in this study. A total of six systems or organizations worldwide were identified to routinely conduct near real-time surveillance. The “automatic linkage and distributed computing” model could effectively improve monitoring efficiency and meet the higher requirements of timeliness. The standardized workflow for near real-time surveillance was summarized as follows: ①Automatic data extraction by computer programs; ②Data standardization using individual-level CDM; ③Regular data submission using aggregate-level CDM; ④Step-by-step analyses involving signal description, detection, and validation. Conclusion Near real-time surveillance has become automatic and regular in several active surveillance systems worldwide. It is believed that this review would serve as a framework for future vaccine-safety endeavors in China to establish a valuable, population-based near real-time surveillance system. References | Related Articles | Metrics

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Self-controlled tree temporal scan statistic in active surveillance of vaccine safety FENG Jingnan, ZHAO Houyu, LIU Zhike, ZHAN Siyan 2023, 20(1): 68-73.  DOI: 10.19803/j.1672-8629.20220546 Abstract ( 102 )   PDF (1372KB) ( 90 )   Objective To introduce the self-controlled tree temporal scan statistic, a novel signal detection method applied to post-marketing active surveillance of vaccine safety, so as to provide reference for proactive surveillance of vaccine safety in China. Methods The principles and status quo of the self-controlled tree temporal scan statistic were presented in this overview based on previous literature. Results and Conclusion This method allows detection of potential vaccine-associated adverse events and adjusts for the multiple testing without prespecifying the specific events or postexposure risk intervals of concern. Despite the fast development of this method globally, it has been rarely reported in China. References | Related Articles | Metrics

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Progress in applications of self-controlled designs in association study of vaccine safety LIU Zhike, ZHAN Siyan 2023, 20(1): 74-78.  DOI: 10.19803/j.1672-8629.20220618 Abstract ( 87 )   PDF (1148KB) ( 110 )   Active surveillance of vaccine safety is a crucial and essential part of the whole evidence chain of vaccine safety, especially for the surveillance of serious adverse reactions following immunization. In recent years, electronic health care databases have been facilitating the active surveillance of vaccine safety and association study. Globally, more than a dozen countries have performed active surveillance of vaccine safety using the electronic health records, medical claim, electronic medical records. The surveillance designs involved cohort study, case control study, and self-controlled study. Self-controlled designs, such as self-controlled case series study and self-controlled risk interval study, have been increasingly used in vaccine safety monitoring outside China. The review outlines the applications of and progress in self-controlled studies in association study of vaccine safety in the hope of contributing to post-marketing surveillance of vaccine risks in the real world. References | Related Articles | Metrics

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Efficacy of lycorine thioester hydrochloride against coxsackievirus A16 in vivo WANG Huiqiang, YAN Haiyan, LI Xingqiong, YANG Jie, LI Yuhuan 2023, 20(1): 79-84.  DOI: 10.19803/j.1672-8629.20220625 Abstract ( 58 )   PDF (2022KB) ( 59 )   Objective To investigate the efficacy of lycorine thioester hydrochloride against coxsackievirus A16 (CVA16) in vivo. Methods A mouse model of CVA16 infection was established via intraperitoneal injection of CVA16 in ICR mice aged 10 to 11 days. The experimental groups were divided into 1.0, 0.5 and 0.25 mg·kg-1 lycorine thioester hydrochloride groups, 50 mg·kg-1 RBV control group, virus control group, and the normal control group. The incidence of infections, survival rate and average survival of mice after virus infection were detected. The expression level of the viral protein in muscle tissue was detected by Western-blot assay. Cytopathic effect assay (CPE) was used to detect the viral titer in muscle tissue. Hematoxylin-eosin(HE) staining was used to detect the pathological changes of muscle tissue. Results Compared with the virus control group, administration of lycorine thioester hydrochloride 1.0 and 0.5 mg·kg-1 could significantly reduce the viral titer and viral protein expression in muscle tissue, mitigate the inflammatory injury caused by CVA16 infection, delay the pathogenesis of mice, significantly prolong the average survival of mice, and increase the survival rate of mice. Conclusion Administration of lycorine thioester hydrochloride 1.0 and 0.5 mg·kg-1 has a significant protective effect on CVA16-infected mice, suggesting that lycorine thioester hydrochloride may be a potential drug for the treatment of hand, foot, and mouth disease (HFMD). References | Related Articles | Metrics

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Liver injury induced by tripterygium glycosides based on P450 enzymes and toxicity reduction of compound glycyrrhizin FU Xiaotong, LIU Ting, CAO Chunyu, ZHANG Haijing, XIA Bing, ZHAO Xiao'ang, WANG Lifang, ZHAO Chunhui, YANG Yifei 2023, 20(1): 85-91.  DOI: 10.19803/j.1672-8629.20220356 Abstract ( 69 )   PDF (2148KB) ( 63 )   Objective To clarify the dose-time-effect relationship of tripterygium glycosides (TG) hepatotoxicity, investigate the mechanism of TG hepatotoxicity in rats based on the regulation of cytochrome P450 enzymes, and explore the mechanism of toxicity reduction of compound glycyrrhizin (CG) with TG in order to ensure safe clinical applications of TG. Methods Thirty male SD rats were randomly divided into the control group, TG 189.0 mg·kg-1 group, TG 472.5 mg·kg-1 group, and TG 189.0 and 472.5 mg·kg-1 respectively combined with CG 20.25 mg· kg-1 groups according to body weight, with 6 rats in each. The drug was administered once daily for three weeks. The serum levels of total protein(TP)、albumin(ALB), aspartate aminotransferase(AST), and alanine aminotransferase(ALT)were measured at 1, 2, and 3 weeks after dosing, respectively. At the end of the last dose, liver coefficients were calculated and histopathological examinations were performed to detect the transcript levels of CYP2B1 and CYP3A1 genes. Results One week after administration, the serum levels of ALB in the TG 189.0 and 472.5 mg·kg-1 groups became lower (P<0.05), but ALT in the TG 472.5 mg·kg-1 group was increased (P<0.01). Three weeks after administration, the level of TP in the TG 189.0, and 472.5 mg·kg-1 groups continued to decrease. After 3 weeks of coadministration with CG, the ALT level in the TG 472.5 mg·kg-1 group decreased (P<0.01) while those of ALB and TP (P<0.05) increased compared with the same dose of TG used alone. After three weeks of administration, rats in the TG 189.0 mg·kg-1 group showed slight swelling of hepatocytes and a small amount of lymphocyte infiltration in the confluent area while those in the TG 472.5 mg·kg-1 group showed an increase in liver weight and liver coefficient compared with the control group (P<0.05, P<0.01). TG at doses of 189.0 and 472.5 mg·kg-1 increased CYP2B1 and CYP3A1 mRNA levels in liver tissues of rats (P<0.05, P<0.01). CYP2B1 mRNA levels were down-regulated after the combination of TG and CG. Conclusion TG administered to rats at doses of 189.0 and 472.5 mg·kg-1 for three consecutive weeks caused different degrees of liver injury. Hepatotoxicity of TG 472.5 mg·kg-1 was more severe, and was more significant three weeks after administration than one week after administration, with a dose time effect relationship. Overexpression of CYP2B1 and CYP3A1 mRNA in rat hepatocytes is one of the mechanisms of toxicity. CG can reduce hepatotoxicity by downregulating the CYP2B1 mRNA level. References | Related Articles | Metrics

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Thyroid immune-related adverse reactions of immune checkpoint inhibitors ZHENG Yi, ZHAI Yinghong, GUO Xiaojing, XU Jinfang, CHI Lijie, GUO Zhijian, CHEN Chenxin, LIANG Jizhou, WEI Lianhui, CHEN Xiao, YE Xiaofei, HE Jia 2023, 20(1): 92-95.  DOI: 10.19803/j.1672-8629.20210968 Abstract ( 152 )   PDF (1195KB) ( 150 )   Objective To explore the feasibility of active monitoring of drugs based on the Chinese Pharmacovigilance System (CHPS) in order to provide data for related research. Methods Based on the data from the CHPS of two sentinel hospitals, the information about tumor patients who had used ICIs and those who had not used ICIs between January 1, 2020 and June 30, 2021 was retrieved as controls. Based on the generalized estimation equation, the thyroid immune-related adverse reactions of ICIs were explored. Results A total of 1 691 patients were included, including 666 in the ICIs group and 1 025 in the control group. The generalized estimating equation model was used to process the follow-up data of patients while taking into consideration all the correlations between repeated measurement data. Tt was found that overt thyrotoxicosis was statistically significant (P<0.05). The incidence was 4.50%, and the median time to onset (TTO) was 41.5 days. Conclusion ICIs may cause overt thyrotoxicosis. When applying ICIs to patients, clinicians should be alert to the occurrence of overt thyrotoxicosis to ensure the safety of medications. References | Related Articles | Metrics

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Mining and research of adverse reaction signals of pneumonia vaccines based on US Vaccine Adverse Event Reporting System LIU Yantao, ZHANG Lingli, LIN Yunzhu, CHEN Li, WANG Li 2023, 20(1): 96-100.  DOI: 10.19803/j.1672-8629.20210956 Abstract ( 214 )   PDF (1349KB) ( 207 )   Objective To provide reference for rational and safe use of pneumonia vaccines by mining and studying the adverse reaction signals of pneumonia vaccines. Methods The reporting odds ratio (ROR) and the proportional reporting ratio (PRR) were used to analyze the adverse reaction reports collected by the American Vaccine Adverse Reaction Event Reporting System (VAERS) between January 1, 2010 and December 31, 2019, while adverse reaction signals related to pneumonia vaccines were mined. Results Thirty-six ADR signals associated with 23-valent pneumonia polysaccharide vaccines were obtained using both the ROR and PRR method, seven of which were not mentioned in specifications before, and ADR with the highest signal intensity were related to leukocytosis. A total of 103 ADR signals of 13-valent pneumococcal polysaccharide conjugate vaccines were obtained using ROR, compared with 102 signals by PRR. Thirty-six of the ADR signals were not mentioned in any specifications before, and ADR with relatively high signal intensity centered on gastrointestinal diseases, infections and invasive diseases, systemic diseases, and various reactions at the administration site. Conclusion It is suggested that patients should be closely monitored for adverse reactions, especially new ADR that are not mentioned in specifications, and immediate interventions should be enforced when pneumonia vaccines are used. References | Related Articles | Metrics

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Quality evaluation of adverse drug reaction reports in oncology department based on weighted Topsis-rank-sum ratio method WU Na, SU Dan, WANG Haikun, SHEN Aizong 2023, 20(1): 101-105.  DOI: 10.19803/j.1672-8629.20220026 Abstract ( 122 )   PDF (1369KB) ( 97 )   Objective To establish a comprehensive system for evaluating the quality of adverse drug reaction (ADR) reports and provide reference for objective evaluation of quality of ADR reports in an oncology department. Methods Quality evaluation standards for ADR reports were established according to the related scoring standards and documents. A combination of weighted Topsis and rank sum ratio (RSR) was used to evaluate and classify the quality of 120 original ADR reports submitted to the Department of Pharmacy by the Department of Oncology at Bozhou People’s Hospital in 2021. Results Twenty reports were of medium quality (Ci＞0.570 0), 75 reports were up to the standard (0.360 0＜Ci≤0.570 0) and 25 reports fell short of the standard (Ci≤0.360 0). The main problems included inadequate descriptions of processes of ADRs, incorrect or incomplete drug information. Conclusion Quality evaluation of ADR reports based on the weighted Topsis–RSR method can help avoid the limitations of a single approach. This method is feasible and effective. The results of evaluation suggest that the quality of ADR reports by the Department of Oncology at our hospital needs to be improved. References | Related Articles | Metrics

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Analysis of agranulocytosis in a child induced by vancomycin injection CAO Xiaoyu, WANG Ying, WANG Jingwen, YANG Ruixia, GE Jie 2023, 20(1): 106-109.  DOI: 10.19803/j.1672-8629.20210813 Abstract ( 190 )   PDF (1257KB) ( 207 )   Objective To provide reference for vancomycin injection induced adverse reaction—neutropenia/agranulocytosis. Methods A case report of four-year-old girl with agranulocytosis caused by vancomycin injection was analyzed by reviewing the related literature. Results A total of four related domestic and foreign reports were retrieved in this paper. It was found that all the five cases suffered from agranulocytosis or neutropenia to different extents after receiving vancomycin injection, and that the patients gradually recovered after vancomycin withdrawal or dosage reduction. Neutropenia in children might be related to the accumulation of vancomycin. Conclusion Routine plasma drug concentrations should be closely monitored when children receive vancomycin injection. The dosage of vancomycin should be reduced or stopped in case of agranulocytosis or neutropenia. If necessary, symptomatic treatments should be given. References | Related Articles | Metrics

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Research progress in substances related to hemolysis risk in glucose-6-phosphate dehydrogenase deficiency LI Jinying, SONG Hongjie, LI Jinqi, GU Haihui, QIAN Baohua 2023, 20(1): 110-116.  DOI: 10.19803/j.1672-8629.20211165 Abstract ( 96 )   PDF (1199KB) ( 97 )   Drug-induced hemolysis is one of the common causes of acute hemolysis in glucose-6-phosphate dehydrogenase deficiency (G6PDd). With the development and marketing of new drugs, cases of drug-induced hemolysis in G6PDd are increasing year by year. This paper lists and updates antibiotics, antivirals, antineoplastics, antipyretics, anti-inflammatory drugs, metabolic drugs, vasodilators, anaesthetics, antidotes, other drugs, herbs, plants, topical drugs, reagents, chemicals and food with hemolysis risk for G6PDd so as to facilitate clinical selection of treatments and warning and prevention of this disease. References | Related Articles | Metrics

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Research progress in enhancing anticoagulant effects of warfarin and the mechanism by traditional Chinese medicine for promoting blood circulation and removing blood stasis LIU Tiantian, CAO Junling, ZHANG Yanli, GONG Ying, GU Yuanyuan 2023, 20(1): 117-120.  DOI: 10.19803/j.1672-8629.20220169 Abstract ( 131 )   PDF (1233KB) ( 219 )   Warfarin is a double coumarin anticoagulant commonly used in clinic. It is widely used in the adjuvant treatment of cardiovascular and cerebrovascular diseases and in the prevention and treatment of thromboembolic diseases. However, its treatment window is narrow, individual differences are huge, and warfarin interacts with a variety of drugs and foods, which is likely to lead to the risk of bleeding or insufficient anticoagulation. Traditional Chinese medicines for promoting blood circulation and removing blood stasis are widely used in the treatment of cardiovascular diseases, and there are many cases where warfarin is used in combination with TCM. Such combination, however, can increase the risk of bleeding. By consulting the literature, this paper found that the mechanism by which traditional Chinese medicines for promoting blood circulation and removing blood stasis can enhance the anticoagulant effect of warfarin mainly involves the interactions of pharmacokinetics and pharmacodynamic effects. It is recommended that when traditional Chinese medicines for activating blood circulation and removing blood stasis and warfarin are used together in clinical practice, the international standardized ratio of patients should be closely monitored, and the dosage of warfarin should be appropriately adjusted in order to prevent the combination of traditional Chinese medicines with additive effects and ensure safe and rational use of drugs. References | Related Articles | Metrics