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.

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.

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 7.3×10 9/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.

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 14×10 6/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.

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 1.8×10 12/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 3.6×10 12/L and hemoglobin 93 g/L. Reexamination at 4 weeks revealed red blood cell count 4.3×10 12/L and hemoglobin 135 g/L.

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.

Objective:To systematically evaluate the incidence and risk factors of acute kidney injury (AKI) induced by vancomycin in pediatric patients.Methods:Databases of PubMed, Embase, The Cochrane Library, Web of Science, CNKI, Wanfang, VIP, Chinese Biomedical Database (CBM) were searched and articles about the risk factors of AKI induced by vancomycin in pediatric patients from inception to June 2024 were collected. Quality assessment was performed using the Newcastle-Ottawa Scale (NOS) for the included studies. Meta-analysis of the data for relevant exposure factors extracted from the included literature was conducted using Rev Man 5.4. The strength of association between the exposure factors and AKI was expressed using the odds ratio ( OR) and its 95% confidence interval ( CI). Results:A total of 13 studies were entered, involving 11 073 patients. Of them, 1 388 patients were in AKI group and 9 685 patients in non-AKI group. The incidence of AKI was 12.53%, ranging from 4.62% to 27.07%. The quality evaluation results showed that the 13 documents were all of high-quality (NOS score ≥7 points). Meta-analysis showed that admission to intensive care unit (ICU) ( OR=2.39, 95% CI: 1.59-3.59, P<0.001), vancomycin using time ≥7 d ( OR=2.19, 95% CI: 1.44-3.34 P=0.003), vancomycin steady-state trough concentration ≥15 mg/L ( OR=2.98, 95% CI: 2.22-4.01, P<0.001), combined with nephrotoxic drugs ≥2 kinds ( OR=2.92, 95% CI=1.84-4.64, P<0.001), combined with piperacillin sodium and tazobactam sodium ( OR=2.71, 95% CI: 1.72- 4.27, P<0.001), combined with carbapenem ( OR=2.36, 95% CI: 1.36-4.10, P=0.002), combined with aminoglycosides ( OR=1.78, 95% CI: 1.35-2.35, P<0.001), combined with loop diuretics ( OR=3.16, 95% CI: 2.36- 4.23, P<0.001), combined with amphotericin B ( OR=2.26, 95% CI: 1.35-3.79, P=0.002), combined with contrast medium ( OR=2.34, 95% CI: 1.04-5.25, P=0.040), and combined with aciclovir ( OR=1.74, 95% CI: 1.04-2.84, P=0.030) were all risk factors of AKI induced by vancomycin in pediatric patients. Conclusions:The incidence of vancomycin-related AKI in pediatric patients was 12.53%. Admission to ICU, vancomycin trough concentration ≥15 mg/L, medication time ≥7 d, and concomitant use of ≥2 nephrotoxic drugs and etc.were risk factors of vancomycin-related AKI.

Objective:To explore the differences on contraindication information for children in domestic and foreign drug instructions, and provide reference for improving the relevant information in Chinese drug insert sheets.Methods:Chinese drug insert sheets of chemicals and biological products contained in the China Pharmacopoeia 2020 and those of the western medicines in the 2023 China′s Basic Medical Insurance, Work-related Injury Insurance and Childbirth Insurance Drug Catalog were collected; drugs that were marked as contraindication for children were selected and relevant contraindication information in the Chinese drug insert sheets was collected. Instructions of the above-mentioned drugs approved by the U.S. Food and Drug Administration (English labels) were also collected, and the information on pediatric medication was reviewed and compared with the Chinese drug insert sheets. Results:A total of 222 drugs were labeled as contraindication for children in the Chinese drug insert sheets, of which 149 were available for their English labels; 123 drugs (17.5%) were not labeled as contraindication for children in English labels, and 26 (82.5%) were labeled. The 123 drugs that were not labeled as contraindication for children in the English labels included the following conditions: 58 were labeled as contraindication for children of some age in the Chinese drug insert sheets but not in the English labels, and relevant medication information was provided; 40 were labeled as contraindication for children of some age group in the Chinese drug insert sheets but was described as the effectiveness and safety of the use for children have not yet been determined for this age group in the English labels; 13 were labeled as contraindication for children in the Chinese drug insert sheets, but the medication information on children in the English labels was not clear or missing; 12 were labeled as contraindicated for children in Chinese drug insert sheets but not in the English labels, only expressed as not yet determined or not recommended for use, etc., with inconsistent age group. Among the 26 drugs labeled as contraindication for children in both Chinese and English instructions, the contraindication age group were the same in above 2 instructions for 20 drugs, and were inconsistent for the other 6 drugs; reasons for contraindication were described in both the 2 instructions for 17 drugs (13 were consistent, 4 were inconsistent), only in English labels for 8 drugs, and only in Chinese drug insert sheets for 1 drug.Conclusions:Many drugs are labeled as contraindication for children in Chinese drug insert sheets, but reasons for contraindication are rarely explained. Differences in children′s age in contraindications exist for some drugs between the Chinese drug insert sheets and English labels. The information on contraindications for children in Chinese drug insert sheets still needs to be further improved.

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.

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.