2025 Volume 27 Issue 5 Published: 29 May 2025
  

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  • Pay attention to basic research on adverse drug reactions
    Meng Yan, Cai Haodong
    2025, 27(5): 257-259. https://doi.org/10.3760/cma.j.cn114015‑20250311‑00133
    Abstract ( ) PDF ( )
    Adverse drug reaction (ADR) is an important problem in clinical diagnosis and treatment, and basic research related to ADR is essential. Exploring the mechanism of ADR through basic research can provide a theoretical basis for formulating effective prevention strategies and targeted treatment programs for ADR; many safety problems found in the process of clinical medication can be effectively verified and solved through basic research, such as the dose?response (toxicity) relationship of drugs and drug interactions; basic research related to drug toxicity is an indispensable key link in the process of drug research and development, and its research results are directly related to the safety of candidate compounds and the feasibility of clinical application. At present, there is a limited amount of literature on the basic research related to the mechanism of ADR in China. It is hoped that more researchers will pay attention to basic research related to ADR and drug safety, and promote the development of this field to a higher level.
  • Study on role of glutathione peroxidase 4‑dependent ferroptosis in diclofenac-induced injury of human kidney tubular epithelial cells
    Chen Shuifang, Chen Hui, Chen Xuemei, Zheng Qianwen, Zheng Dong
    2025, 27(5): 260-267. https://doi.org/10.3760/cma.j.cn114015‑20240802‑00679
    Abstract ( ) PDF ( )
    Objective To explore the role of glutathione peroxidase 4 (GPX4)-dependent ferroptosis in diclofenac-induced kidney injury.　Methods Human kidney tubular epithelial cells (HK-2 cells) were cultured and then divided into 3 groups: control group, diclofenac group, and iron death inhibitor ferrostatin-1 (Fer-1) group. The same amount of 1% Fer-1 (final concentration 10 μmol/L) and phosphate buffered saline was respectively added to cells in the Fer-1 group and the other 2 groups. After 48 hours of culture, diclofenac 200 μmol/L was added to cells in the diclofenac group and the Fer-1 group. The cell viability of each group was detected by cell counting kit-8 (CCK-8). The cell cycle, apoptosis and intracellular reactive oxygen species (ROS) levels were detected by flow cytometry. The levels of intracellular iron ion, lactate dehydrogenase (LDH), malondialdehyde (MDA) and GPX4 were detected by enzyme-linked immunosorbent assay. The expression level of GPX4 was detected by Western blotting method.　Results Compared with the control group, the cell viability and G1 phase cell percentage of the diclofenac group were significantly lower, and compared with the diclofenac group, those were significantly higher (all P<0.05). The apoptosis rate of diclofenac group was significantly higher than that of the control group (P<0.05), but there was no significant difference in apoptosis rate between Fer-1 group and diclofenac group (P>0.05). Compared with the control group, the intracellular ROS, iron content, LDH, and MDA levels were significantly higherin the diclofenac group, while the expression level of GPX4 was lower (all P<0.05). However, the ROS, iron content, LDH, and MDA levels in the Fer-1 group were lower than those in the diclofenac group, while GPX4 expression was higher than that in the diclofenac group (all P<0.05).　Conclusion Diclofenac can induce ferroptosis in HK-2 cells and inhibiting the ferroptosis can alleviate cell injury, suggesting that GPX4-dependent ferroptosis may be involved in kidney injury induced by diclofenac.
  • Study on the effect of Shenxianling granules (参仙灵颗粒) on the pharmacokinetics of ondansetron
    Lan Xiaohong, Zhou Yonggang, Wei Wei, Zhang Ye, Chen Ying, Li Xiang, Chen Shudong
    2025, 27(5): 268-273. https://doi.org/10.3760/cma.j.cn114015‑20240806‑00690
    Abstract ( ) PDF ( ) Supplementary files
    Objective To explore the effect of Shenxianling granules on the pharmacokinetics of ondansetron.　Methods A method for detecting the plasma concentration of ondansetron using highperformance liquid chromatography (HPLC) was established. The reliability of the method was validated through specificity, linear relationship, precision, stability, repeated experiments, and sample recovery rate testing. Thirty six healthy male New Zealand rabbits were randomly divided into 2 groups, with 18 rabbits in each group. Rabbits in the single ondansetron group (single drug group) received intravenous injection of ondansetron 0.92?mg/kg through the ear vein. Rabbits in the Shenxianling granules combined with ondansetron group (combination drug group) were firstly given 575 mg/kg of Shenxianling granules by gavage continuously for 10 days, and on the morning of the 11th day, ondansetron 0.92?mg/kg was intravenously injected. Blood samples were collected before administration and at 5 minutes, 10?minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 10 hours and 24 hours after administration of ondansetron. The blood concentration of ondansetron was detected using HPLC method and pharmacokinetic parameters were calculate.　Results Two New Zealand rabbits in the combination drug group developed agitation and cough, and then died on the second and fifth day of gavage, respectively. Therefore a total of 18 and 16 rabbits in the single drug group and the combination drug group completed the experiment, respectively. After ondansetron administration, the plasma concentration of ondansetron increased rapidly in the single drug group and remained at low levels in the combination drug group. From 5 minutes to 10 hours after administration, the plasma concentration of ondansetron at the 13 blood sampling time points in the combination drug group was significantly lower than that in the single drug group, and the differences were statistically significant (all P<0.001). Compared with the single drug group, the plasma clearance half?life of ondansetron in the combination drug group was significantly prolonged, the peak time, peak concentration, concentration at the last time and area under the curve (AUC) were all significantly reduced, and the percen- tage of residual or extrapolated area to the overall AUC, apparent volume of distribution, and clearance/bioavailability ratio were significantly increased; the differences were statistically significant (all P<0.001).　Conclusions There is a significant interaction between Shenxianling granules and ondansetron, leading to a decreased plasma concentration of ondansetron. The mechanism may be related to Shenxianling granules altering the tissue distribution of ondansetron within the body.
  • Study on biodistribution of mixed activated killer immune cells in immunodeficient mice after administration
    Zhao Manman, Jiang Lijun, Zhao Jing, Jiang Hua, Huang Ying, Wen Hairuo, Zhou Xiaobing
    2025, 27(5): 274-280. https://doi.org/10.3760/cma.j.cn114015-20240809-00707
    Abstract ( ) PDF ( )
    Objective To explore the biodistribution characteristics of mixed activated killer (MAK) immune cells in immunodeficient mice after administration.　Methods Ninety-six immune immunodeficient (NOG) mice (half male and half female) were equally divided into MAK cell group and solvent control group. The MAK cell group mice were injected with DiR-labeled MAK cells via the tail vein, while those in the solvent control group were injected with an equal amount of solvent via the tail vein. The number of MAK cells in the peripheral blood of mice was detected using a flow cytometry at 11 time points from 15 minutes to 84 days after administration. The distribution of MAK cells in mice was measured using in vivo bioluminescence imaging at 18 time points from 5 minutes to 84 days after administration. And at 8 time points from 3 hours to 84 days after administration, the heart, liver, spleen, lungs, kidneys, brain, stomach, duodenum, colon, bone marrow, fat, skeletal muscle, testes/uterus, epididymis/ovary, and blood were collected from corresponding mice. The DNA levels of MAK cells in blood and various organs of these mice were detected using fluorescence real time quantitative polymerase chain reaction (qPCR) method.　Results The flow cytometry results showed that MAK cells could be detected in the peripheral blood of mice 15 minutes after administration, and the highest number of MAK cells in blood appeared during 3 hours to 1 day. By 14 days after administration, MAK cells were almost undetectable in peripheral blood of mice. In vivo bioluminescence imaging results showed that the fluorescence intensity of MAK cells in mice was strongest on days 1 and 2 after administration, and MAK cells were mostly distributed in the liver, spleen, lung, and leg bone of mouse. The qPCR detection results showed that MAK cells were mainly distributed in the spleen and lungs. High levels of MAK cell DNA amplification were observed in organs such as the spleen and lungs 28-56 days after administration, and a certain amount of MAK cell DNA could still be detected in organs of mice such as the spleen at 84 days.　Conclusions After administration, MAK cells were mainly distributed in the spleen, lung, liver and other organs of NOG mice. From 28 to 56 days after administration, MAK cells are significantly activated and proliferate, and a certain amount of MAK cell DNA can still be detected in the spleen and other organs after 84 days in mice.
  • Analysis of adverse events of Fufang E′jiao (复方阿胶浆) syrup based on literature
    Chen Zijia, Chen Zhiqing, Peng Wenxi, Wang Zhifei, Xie Yanming
    2025, 27(5): 281-287. https://doi.org/10.3760/cma.j.cn114015-20240614-00444
    Abstract ( ) PDF ( )
    Objective To evaluate the clinical safety of Fufang E‘jiao syrup and provide reference for its rational and safe clinical use.　Methods The literature involving Fufang E'jiao syrup in domestic and international databases, as well as the relevant clinical trials on ClinicalTrials.gov and the Chinese Clinical Trial Registry website were searched up to June 1, 2024. Those literature and clinical trials reporting drug adverse events were included, and the basic information about literature/clinical trials (title, publication year, study design, etc.), patients (age, gender, primary diseases, and dosage of Fufang E'jiao syrup), and adverse events (time of occurrence, clinical manifestations, and outcomes) was extracted. The adverse events were standardized and classified using the Medical Dictionary for Regulatory Activities version 25.0, and were also analyzed based on traditional Chinese medicine theory.　Results A total of 19 literature were included in the analysis, including 16 observational/experimental clinical studies, and 3 case reports. The 19 literature reported a total of 430 adverse events involving 398 patients, and the patients were mainly with malignant tumors and anemia. The 430 adverse events involved 11 system organ classes, which mainly included gastrointestinal disorders (260 events, 60.47%, with the most common symptom being dry mouth), respiratory, thoracic, and mediastinal disorders (119 events, 27.67%, with the most common symptom being dry throat), and skin and subcutaneous tissue disorders (16 events, 3.72%, with the most common symptom being mucosal ulcers). Based on traditional Chinese medicine theory, the 430 adverse events were mainly manifested as symptoms of indigestion (nausea, epigastric discomfort, and decreased appetite) and symptoms of “heat” (dry mouth and dry throat).　Conclusions Fufang E'jiao syrup has a relatively good overall safety profile, with the most common adverse events being symptoms of “heat” and gastrointestinal reactions. Patients should not use it blindly, and it should be used with syndrome differentiation in clinical practice.
  • Comparative study on application efficacy of different surveillance methods in postmarketing safety evaluation of group A and C meningococcal polysaccharide vaccine
    Shi Xiaowen, Li Chang, Fang Wenjian, Du Lin
    2025, 27(5): 288-296. https://doi.org/10.3760/cma.j.cn114015-20241011-00087
    Abstract ( ) PDF ( )
    Objective To compare and analyze the application efficacy of active surveillance versus passive surveillance in post-marketing safety monitoring of the group A and C meningococcal polysaccharide vaccine(MPSV-AC).　Methods Safety data for MPSV-AC from its market launch in November 2011 to June 2024 were collected from Beijing Zhifei Lyuzhu Biopharmaceutical Co., Ltd., and categorized into active and passive surveillance data based on acquisition methods. Active surveillance data were derived from adverse events cases observed in the company′s phase Ⅳ clinical trial. Passive surveillance data were carried out by the Pharmacovigilance Department through the drug adverse reaction direct reporting system, which downloaded all adverse events following immunization(AEFI) case reports. Cases of adverse events under active surveillance that were "definitely related", "probably related", "possibly related", or “possibly unrelated” were classified as adverse reaction cases, and cases of passive surveillance that were classified as "general reaction" or "abnormal reaction" were classified as adverse reaction cases, and were counted according to the number of cases. For cases where different clinical manifestations of adverse reactions or preferred terminology were present in the same one patient, the number was counted separately. Descriptive epidemiological methods were used to describe the incidence of adverse reaction reports, the distribution of clinical manifestations, adverse reactions recorded and not recorded in the instructions and adverse reactions outcomes of two monitoring methods. The differences in the incidence of reported adverse reactions between active and passive surveillance were compared and analysed.　Results A total of 922 patients with MPSV-AC adverse reaction reports were obtained through two monitoring modes, and 1 308 adverse reactions were occurred. In the active surveillance, the number of vaccination doses was 9 999, and 579 patients with adverse reactions were reported with 911 adverse reactions. In the passive surveillance, the number of vaccination doses was 4 185 800, and 343 patients with adverse reactions were reported with 397 adverse reactions. The incidence of reported adverse reactions in the passive surveillance was lower than in the active surveillance, and the difference was statistically significant ［0.008% (343/4 185 800) vs. 5.791% (579/9 999), P<0.001］. The age range for active surveillance was ≥2 to<7 years old; the age range of passive surveillance was 0-15 years old, with the highest proportion of those aged ≥2 to<7 years old ［79.30% (273/343)］. The clinical manifestation that topped the composition ratio of major adverse reactions for both surveillanceme thods was fever, but systemic symptoms such as malaise and anorexia were more frequently reported in active surveillance, whereas signs visible on the surface such as allergic rash, erythema and hard nodules were reported in passive surveillance. The proportion of serious adverse reactions from active surveillance was 0.22%(2/922), which were upper respiratory tract infection and febrile convulsions. Of the adverse reactions not included in the specification, those from active surveillance mainly involved infections and invasive diseases ［77.32% (75/97)］, and those from passive surveillance mainly involved diseases of the skin and subcutaneous tissues(6/12). All 579 patients in the active surveillance adverse reaction reports were monitored until cured; in the passive surveillance, 199 cases (50.13%, 199/397) were cured, 168 cases (42.32%, 168/397) were improved, and 30 cases (7.56%, 30/397) were unknown.　Conclusions Active surveillance is irreplaceable for postmarketing safety evaluation of vaccines, as it comprehensively captures safety signals, indicating good safety of MPSV-AC. A multi-source data integration platform could be established in the future.
  • Clinical case analysis of dissociative symptoms caused by esketamine hydrochloride nasal spray in treatment of treatment resistant depression
    Deng Qiying, Tian Shanshan, Wu Tingfang, Li Anning, An Fengrong, Wang Gang
    2025, 27(5): 296-302. https://doi.org/10.3760/cma.j.cn114015-20250303-00110
    Abstract ( ) PDF ( )
    Objective To analyze the clinical characteristics of dissociative symptoms induced by esketamine hydrochloride nasal spray in patients with treatment-resistant depression (TRD).　Methods The medical records of patients in phase Ⅲ clinical trials for the treatment of TRD who received esketamine hydrochloride nasal spray in Beijing Anding Hospital, Capital Medical University from June 2018 to February 2021 were collected. The general situation of patients (age, gender, comorbid diseases, etc.), the medication of esketamine hydrochloride nasal spray, the combined use of antidepressants, the time from medication to the occurrence of dissociative symptoms each time, duration, severity, evaluation results of causal relationship with esketamine application, intervention and prognosis were recorded, and a retrospective descriptive statistical analysis was performed.　Results A total of 21 patients with TRD were enrolled in the study, including 17 (81.0%) with dissociative symptoms, 10 males and 7 females; the age ranged from 20 to 53 years, with a median age of 36 years. All patients were treated with esketamine hydrochloride by nasal spray. The first dose was 56 mg, and the other seven doses were 56 mg or 84 mg, twice a week, lasting for 4 weeks. The 17 patients were all given combination treatment with oral antidepressants. A total of 88 times of dissociative symptoms occurred in the 17 patients. The time from medication to the onset of dissociative symptoms ranged from 4 to 128 min, with a median time of 15 min. The duration of dissociative symptoms ranged from 12 to 326 minutes, with a median time of 70 minutes. The dissociative symptoms were mostly mild. The causal relationship analysis between the esketamine hydrochloride nasal spray and the dissociative symptoms showed that it was definitely related in 6 cases, probably in 1 case, and possibly in 10 cases. The dissociative symptoms in all patients were subsided without intervention.　Conclusions Esketamine hydrochloride nasal spray can cause dissociative symptoms in patients with TRD, most of which occur within 30 minutes after the treatment. The duration of symptoms in most patients is less than 120 minutes, most of which are mild and can subside on their own, and the prognosis is good.
  • Research progress on prescribing cascade identification and management
    Wang Xin, Wang Zimin, Chen Bing, Cai Haodong
    2025, 27(5): 303-307. https://doi.org/10.3760/cma.j.cn114015-20241104-00129
    Abstract ( ) PDF ( )
    Prescribing cascade is a common inappropriate drug use, which will produce and amplify the risk of polypharmacy, causing unrecognized adverse drug reactions or drug-induced diseases, but it is often ignored by clinicians and pharmacists. Prescribing cascade can not only cause harm to patients, but also lead to waste of medical resources and increases the medical burden. This paper reviews the related research progress of the prevention, identification and management of the prescribing cascade, and puts forward suggestions on the identification, termination and research methods of the prescribing cascade. Chinese medical staff should improve their understanding of prescribing cascade, strengthen relevant research, understand the current situation and characteristics of prescribing cascade in China, formulate a list of prescription cascade and study relevant management strategies.
  • Risk and prevention of perioperative pulmonary aspiration caused by delayed gastric emptying associated with semaglutide
    Xue Wenxin, Hao Tianlong, Chen Wei, Wang Jingxin, Cao Keming
    2025, 27(5): 308-312. https://doi.org/10.3760/cma.j.cn114015-20240729-00657
    Abstract ( ) PDF ( )
     Semaglutide is a long-acting glucagon-like peptide-1 receptor agonist (GLP-1RA), which is commonly used in the treatment of type 2 diabetes mellitus and weight loss. Its weight loss effect was exerted mainly by suppressing appetite, delaying gastric emptying, promoting energy metabolism, and accelerating lipolysis. However, delayed gastric emptying can lead to residual gastric content, increasing the risk of pulmonary aspiration during anesthesia. This article reviews the effects and mechanisms of semaglutide on gastric emptying, and proposes preventive measures for perioperative pulmonary aspiration in patients treated with semaglutide by reviewing case reports and clinical studies on semaglutide-related delayed gastric emptying. This provides a reference for the safety of semaglutide treatment during the perio- perative period.
  • Acute kidney injury caused by Jingyaokang capsules（颈腰康胶囊）
    Qiu Yanlong, Huang Min, Li Xiudong, Liu Jinyan
    2025, 27(5): 313-315. https://doi.org/10.3760/cma.j.cn114015-20240918-00049
    Abstract ( ) PDF ( )
     A 66-year-old female patient self-administered Jingyaokang capsules (a compound preparation of traditional Chinese medicines， 3 capsules thrice daily orally) due to lumbar pain. The patient developed oliguria and edema of bilateral lower limbs after 3 doses of medication on the same day. The laboratory tests showed WBC 7.3×109/L, neutrophil percentage 0.70, blood urea 12.7 mmol/L, blood crea- tinine 179 μmol/L, and blood uric acid 461 μmol/L. The kidney function tests 15 days ago showed no abnormalities in the patient. Acute kidney injury caused by Jingyaokang capsules was considered. The drug was stopped and symptomatic treatments including torasemide and maintenance of fluid balance were given. The patient′s urine output gradually increased. Five days later, the patient′s edema of bilateral lower limbs disappeared, and her blood urea and creatinine decreased to normal range. The acute kidney injury in the patient may be related to strychni semen component in the Jingyaokang capsules.
  • Autoimmune encephalitis induced by sintilimab
    Wang Quan, Zhao Junwu, Fang Wei, Li Jinfeng
    2025, 27(5): 315-317. https://doi.org/10.3760/cma.j.cn114015-20240130-00071
    Abstract ( ) PDF ( )
    A 61-year-old female patient was treated with sintilimab (200 mg by intravenous infusion on the first day, 21 days as a cycle) for lung adenocarcinoma and multiple lymph node metastases in the left hilum and mediastinum (10 cycles in total). Headache and dizziness in the patient occurred about 1 month after the last medication. Cerebrospinal fluid examination showed white blood cell count 14×106/L, total protein 799.8 mg/L, Pandy′s test (+), immunoglobulin G 70.8 mg/L, and glucose and chloride within the reference value range. The antibodies against N-methyl-D-aspartate receptor in cerebrospinal fluid and serum were all positive. The patient was diagnosed as having sintilimab-induced autoimmune encephalitis. After receiving methylprednisolone sodium succinate by intravenous infusion for 7 days, the patient′s headache and dizziness were alleviated. After that, the methylprednisolone sodium succinate was switched to oral prednisone acetate tablets. At a 2 month follow-up, no symptoms of headache or dizziness recurred in the patient.
  • Endometrial hyperplasia and severe anemia induced by toremifene
    Li Bao, Li Jie, Sun Xiubo, Yu Ling
    2025, 27(5): 318-320. https://doi.org/10.3760/cma.j.cn114015-20240719-00612
    Abstract ( ) PDF ( )
    A 42-year-old female patient received toremifene 60 mg orally once daily for 5 years after breast cancer surgery. She had a regular menstrual cycle and no history of abnormal bleeding. For more than 1 month, she experienced irregular vaginal bleeding, which worsened for 3 days. The transvaginal color doppler ultrasound revealed endometrial thickening, and laboratory tests showed red blood cell count 1.8×1012/L and hemoglobin 35 g/L. The clinical diagnosis was abnormal uterine bleeding, endometrial thickening, and severe anemia. Symptomatic and supportive treatments, such as hemocoagulase, human erythropoietin, oxytocin, cefuroxime, and blood transfusion were given immediately. Civen the suspicion that toremifene-induced endometrial hyperplasia was the cause of abnormal uterine bleeding, toremifene was discontinued the following day. The symptomatic treatments （including blood transfusion） were continued, and iron supplementation was given. On the third day after discontinuation of toremifene, the patient underwent diagnostic hysteroscopic curettage. The postoperative pathological examination showed endometrial hyperplasia. The next day, the patient had no significant vaginal bleeding, with red blood cell count 3.6×1012/L and hemoglobin 93 g/L. Reexamination at 4 weeks revealed red blood cell count 4.3×1012/L and hemoglobin 135 g/L.
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