To investigate the protective effect and underlying mechanism of kaempferol (Kae) on flap ischemia-reperfusion injury (FIRI) in rats by regulating glutathione peroxidase 4 (GPX4)-mediated ferroptosis and gasdermin D (GSDMD)-mediated pyroptosis.

McFarlane method was used to establish the ischemia-reperfusion model of rat dorsal flap. A total of 91 SPF SD rats were randomly divided into sham group, model group, experimental group, agonist group, inhibitor group, Kae+agonist group and Kae+inhibitor group, with 13 rats in each group. After successful modeling, the experimental group was given kaempferol 50 mg·kg^-1 by gavage; the agonist group was intraperitoneally injected with 2 mg·kg^-1 NOD like receptor thermoprotein domain associated protein 3 (NLRP3) activator once a week; the inhibitor group was intraperitoneally injected with 30 mg·kg^-1 disulfiram once a week; the Kae+agonist group received intraperitoneal injection of 2 mg·kg^-1 NLRP3 activator+50 mg·kg^-1 kaempferol; the Kae+inhibitor group received intraperitoneal injection of 30 mg·kg^-1 disulfiram+50 mg·kg^-1 kaempferol for 2 weeks. The iron content in tissues was detected by iron content detection kit; the levels of serum interleukin-1 β (IL-1 β) and IL-18 were detected by enzyme linked immunosorbent assay (ELISA); the expressions of proliferating cell nuclear antigen (Ki67) and platelet endothelial cell adhesion molecule-1 (CD31) were detected by immunohistochemistry; the protein expressions of GPX4, Caspase-1 and GSDMD-NT were detected by Western blot.

The flap survival rates of the sham group, model group, experimental group, agonist group, inhibitor group, Kae+agonist group and Kae+inhibitor group were (96.73±1.10)%, (67.04±1.60)%, (85.39±1.22)%, (57.96±1.52)%, (75.80±1.72)%, (80.28±0.95)% and (90.49±0.76)%, respectively; the tissue iron content levels were (11.57±4.89), (68.04±7.64), (43.87±9.13), (85.97±8.41), (47.78±11.11), (69.68±6.17) and (29.36±7.66) μmol·L^-1; the levels of IL-1 β were (43.83±13.96), (246.02±37.60), (172.19±29.46), (354.39±36.05), (153.56±26.89), (271.13±39.54) and (97.53±24.67) pg·mL^-1, respectively; the relative expression levels of CD31 were 6 694.96±711.29, 2 126.32±277.21, 3 592.33±317.33, 484.36±56.24, 3 568.83±316.65, 1 901.66±383.85 and 4 804.18±360.03, respectively; the relative expression levels of Ki67 were 75.56±6.57, 24.11±4.02, 37.94±4.08, 12.17±2.28, 38.01±3.80, 24.32±2.76 and 54.65±7.01, respectively; the relative expression levels of GPX4 were 0.92±0.02, 0.30±0.07, 0.47±0.08, 0.12±0.04, 0.47±0.08, 0.27±0.07 and 0.62±0.13, respectively; the relative expression levels of Caspase-1 were 0.08±0.03, 0.40±0.07, 0.29±0.04, 0.68±0.07, 0.28±0.03, 0.40±0.06 and 0.18±0.06, respectively; the relative expression levels of GSDMD were 0.06±0.04, 0.57±0.05, 0.30±0.04, 0.93±0.09, 0.30±0.03, 0.56±0.07 and 0.16±0.02 respectively. There were statistically significant differences in the above indexes between model group and sham group, between experimental group and model group, and between Kae+agonist group, Kae+inhibitor group and experimental group (all P<0.05).

Kaempferol can alleviate flap ischemia-reperfusion injury in rats, and its protective effect may be related to upregulating GPX4 expression, inhibiting ferroptosis, and regulating the NLRP3/Caspase-1/GSDMD pyroptosis signaling pathway.

To investigate the role of the phosphatidyqinositol-3 kinase / protein kinase B / nuclear factor-erythroid 2 related factor 2 (PI3K/Akt/Nrf2) pathway in remifentanil postconditioning-induced protection against myocardial ischemia-reperfusion (IR) injury in rats.

Establishing a rat model of myocardial ischemia-reperfusion injury (MIRI) by left anterior descending coronary artery ligation. Subsequently, the rats were randomly assigned to the following groups: control (only threading was performed without ligation), model (ischemia was induced for 30 minutes followed by 30 minutes of reperfusion), experimental (remifentanil was continuously infused by at a dose of 10 μg·kg^-1·min^-1 from 25 minutes of ischemia to 5 minutes before reperfusion), LY294002 (while receiving remifentanil intervention, 0.3 mg·kg^-1 LY294002 was administered), and ML385 (while receiving remifentanil intervention, 30 mg·kg^-1 ML385 was administered). Serum levels of interleukin-6 (IL-6), IL-1β and tumor necrosis factor-alpha (TNF-α) were measured using enzyme-linked immunosorbent assay (ELISA). Apoptosis index (AI) of myocardial cells in each group was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). The expression levels of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt) were measured using real-time quantitative polymerase chain reaction.

The measured parameters for the control, model, experimental, LY294002, and ML385 groups were as follows. Serum interleukin-6 (IL-6) were 0.76±0.15, 3.44±0.35, 1.46±0.37, 3.17±0.28 and 3.07±0.18. IL-1β were 0.34±0.08, 1.18±0.21, 0.66±0.28, 0.94±0.13 and 0.81±0.25, respectively. Serum tumor necrosis factor-α (TNF-α) were 0.98±0.17, 2.38±0.27, 1.17±0.21, 2.27±0.26 and 2.66±0.16, respectively. Apoptosis index (AI) were 0.95±0.67, 20.73±1.63, 10.20±2.48, 15.69±2.41 and 16.31±1.55, respectively. PI3K mRNA relative expression level were 1.00±0.08, 1.69±0.15, 1.90±0.12, 0.98±0.14 and 1.78±0.13, respectively. Akt mRNA relative expression level were 1.00±0.09, 1.56±0.22, 1.85±0.13, 0.87±0.21 and 1.69±0.31, respectively. Nrf2 mRNA relative expression level were 1.00±0.08, 2.62±0.16, 3.11±0.28, 1.37±0.25 and 1.03±0.14, respectively. Statistically significant differences were observed for all the above parameters when comparing the experimental group with the model group, and when comparing the LY294002 and ML385 groups with the experimental group (P<0.05, P<0.01, P<0.001, P<0.0001).

Remifentanil postconditioning exerts a protective effect on myocardial IR injury by reducing IR-induced cardiomyocyte apoptosis and inflammatory response in rats, and may be related to the PI3K / Akt / Nrf2 signaling pathway.

To establish an ultra-high performance liquid chromatography-tandem mass spectrometry method for the determination of 14 sedative hypnotics and their metabolites in serum and urine.

Serum or urine samples were treated with acetonitrile to precipitate proteins. Separated on an Agilent EclipsePlus C18 RRHD column, the liquid was eluted with 0.1% formic acid in water and methanol, at a flow rate of 0.30 mL·min^-1 and column temperature of 35 ℃. Quantified by the internal standard method, and multiple reaction monitoring (MRM) was performed by electrospray ionization (ESI⁺). The method was evaluated for specificity, standard curves and limits of quantification, precision and recovery, matrix effects, and stability. This method was applied to test the proficiency testing samples from the 2023 National Medical Emergency Toxicant Detection Laboratory Comparison Program, including qualitative and quantitative test samples for emergency poisoning assessment of sedative-hypnotic drugs in serum.

The method demonstrated good specificity, with no cross-interference between the various sedative hypnotics and their metabolites. The linear range of 14 sedative hypnotics and metabolites were 1.00-45.00 μg·L^-1, with a correlation coefficient greater than 0.998 2, the detection limit in serum and urine was 0.30 μg·L^-1, and the quantification limit was 1.00 μg·L^-1. In serum, recovery rates at three spiked levels (10.00, 50.00 and 200.00 μg·L^-1) ranged from 85.60% to 105.20%, with relative standard deviations (RSD) between 0.73% and 4.45%. In urine, recovery rates ranged from 88.93% to 108.12%, with relative standard deviations between 0.50% and 6.92%. Fluphenazine hydrochloride and clozapine were identified by this method. The two determined quantitative concentrations of fluphenazine hydrochloride were 339.00 μg·L^-1 and 349.00 μg·L^-1 , with an average value of 344.00 μg·L^-1 and a deviation of 2.90%. The two determined quantitative concentrations of clozapine were 1 668.00 μg·L^-1 and 1 707.00 μg·L^-1 , with an average value of 1 688.00 μg·L^-1 and a deviation of 2.30%. The final feedback result was satisfactory.

This method is rapid and accurate, making it suitable for emergency poisoning detection of sedative hypnotics. Its application to the blind sample detection of emergency poisoning cases is satisfactory.

To conduct data mining on tepotinib-associated adverse drug events (ADEs) using the US FDA Adverse Event Reporting System (FAERS) database, providing evidence for its clinical safety.

ADE reports for tepotinib from FAERS (Q1 2021 to Q4 2024) were analyzed. Signal detection methods included the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), and Multi-item Gamma Poisson Shrinker (MGPS). Sex-based differences in ADE signals were assessed using Fisher’s exact test with Bonferroni correction.

A total of 523 ADE reports identified tepotinib as the primary suspect drug, revealing 37 positive Preferred Terms (PT) across 14 System Organ Classes (SOCs). Notably, ADEs involving the ear and labyrinth disorders, infections and infestations, and nervous system disorders were not documented in the drug label. Several PTs—including malignant pleural effusion, infectious pleural effusion, central nervous system metastasis, pneumothorax, deafness, pericardial effusion, and dysgeusia—were newly identified as potential risks. Sex-stratified analysis showed higher diarrhea risk in women and a stronger appetite loss association in men. Importantly, interstitial lung disease (ILD) exhibited a significant signal in men (ROR=16.28, ROR025=8.71) but not in women, suggesting sex may be a key risk factor for tepotinib-induced ILD.

Clinicians should prioritize monitoring high-frequency, high-signal, and newly detected ADEs during tepotinib therapy. The drug label should be updated to include sex-specific ILD risk warnings.

Based on the adverse event reporting system (FAERS) database of the US Food and Drug Administration (FDA), drugs related to pseudomembranous colitis (PMC) were identified to provide a reference for clinical safe medication.

Extract the reports of drug-related adverse events (AEs) of PMC from the FAERS database for the period from the first quarter of 2004 to the fourth quarter of 2024. Risk signal detection was performed using the reporting odds ratio (ROR) and proportional reporting ratio (PRR) methods. Analysis was conducted on the top 20 drugs in terms of the number of reports and the top 20 drugs in terms of signal values.

A total of 18 356 cases of drug induced PMC were retrieved, and 485 drugs with positive risk signals were identified. The proportion of females was the highest, accounting for 52.09% (9 562 cases/18 356 cases). The number of patients over 60 years old was the largest, accounting for 36.88% (6 769 cases/18 356 cases). Among drug-related diagnoses, Crohn’s disease accounted for 5.67% (1 040 cases/18 356 cases) and ulcerative colitis for 5.53% (1 016 cases/18 356 cases), with a larger number of cases. Among the patient outcomes, the hospitalization-initial or prolonged rate was the highest, accounting for 50.43% (9 257 cases/18 356 cases). Among the top 20 drugs by number of reports, infliximab ranked first. According to the ATC classification, antineoplastic and immunomodulating agents and anti-infectives for systemic use were the most numerous, each accounting for 30% (6 varieties/20 varieties), among which vedolizumab was not mentioned PMC in the label. In the top 20 drugs ranked by ROR signal intensity, anti-infective drugs accounted for the highest proportion of 60% (12 varieties/20 varieties), and belladonna was not mentioned in relation to PMC in the label.

A variety of drugs can cause PMC. Clinicians should remain vigilant, promptly perform diagnostic evaluations, discontinue the offending drugs, and initiate appropriate treatment to ensure medication safety.

To explore the efficacy of eravacycline combined with colistimethate sodium in treating sepsis caused by carbapenem-resistant Escherichia coli producing New Delhi metallo-β-lactamase (NDM) secondary to complex intra-abdominal infection.

The anti-infection regimen was dynamically adjusted according to abdominal-pelvic enhanced MRI, laboratory tests, changes in main inflammatory indicators (peripheral blood white blood cell count and procalcitonin), and drug sensitivity test results.

After 13 days of treatment with eravacycline (50 mg, q12h) and colistimethate sodium (150 mg, q12h), the patient's condition and inflammatory indicators improved significantly, with no drug-related adverse reactions during hospitalization.

The combination is safe and effective for the above-mentioned sepsis, providing crucial technical support for clinical treatment of NDM-producing carbapenem-resistant Escherichia coli infections.