To discuss the effects of esculetin on myocardial ischemia-reperfusion injury in rats by regulating the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway.

A total of 60 rats were randomly divided into control group, model group, low-dose (L)-esculetin (20 mg·kg^-1) experimental group, high-dose (H)-esculetin (40 mg·kg^-1) experimental group, and H-esculetin+inhibitor (40 mg·kg^-1 esculetin and 20 mg·kg^-1 JAK2/STAT3 inhibitor WP1066) group, with 12 rats in each group. Except for the control group, rats in all other groups were subjected to myocardial ischemia-reperfusion modeling. Triphenyltetrazolium chloride (TTC) staining was used to evaluate infarct size; hematoxylin-eosin staining (HE) staining was used to observe histopathological changes; TdT-mediated dUTP Nick-End Labeling (TUNEL) staining was used to observe myocardial apoptosis; enzyme linked immunosorbent assay (ELISA) was used to detect inflammatory cytokines; Western blot was used to detect protein expression of JAK2/STAT3 pathway in rat myocardium.

The cardiomyocytes of the rats in the model group were enlarged and arranged in a disorderly manner, while the myocardial damage of rats in the L-esculetin group and the H-esculetin experimental group was reduced. The myocardial infarction areas of the rats in the control group, model group, L-esculetin experimental group, H-esculetin experimental group and H-esculetin+inhibitor group were (3.24±0.35)%, (31.36±3.51)%, (20.75±2.37)%, (10.48±1.16)% and (29.56±3.27)%, respectively; the cardiomyocyte apoptosis rates were (6.37±0.75)%, (56.24±6.03)%, (38.72±3.94)%, (21.46±2.37)% and (51.05±5.28)%, respectively, the levels of interleukin-1β (IL-1β) were (9.34±1.02), (158.95±16.83), (125.49±13.26), (94.83±10.54) and (151.27±16.42) pg·mL^-1, respectively; the levels of interleukin-18 (IL-18) were (13.27±1.46), (568.93±59.95), (486.38±51.32), (312.63±33.41) and (527.46±56.25) pg·mL^-1, respectively; the levels of tumor necrosis factor-α (TNF-α) were (7.85±0.98), (124.84±14.64), (88.95±9.63), (53.58±5.97) and (116.32±13.27) pg·mL^-1, respectively; the relative expression levels of pentraxin 3 (PTX3) protein were 0.86±0.11, 0.32±0.04, 0.53±0.07, 0.71±0.08 and 0.69±0.08, respectively; the relative expression levels of phospho-JAK2 (p-JAK2) protein were 0.81±0.09, 0.36±0.05, 0.54±0.07, 0.73±0.08 and 0.39±0.05, respectively; the relative expression levels of phospho-STAT3 (p-STAT3) protein were 0.78±0.09, 0.29±0.04, 0.52±0.06, 0.74± 0.09 and 0.33±0.04, respectively. Comparing the control group with the model group, the model group with the L-phenithin experimental group, the L-phenithin group with the H-phenithin experimenal group, and the H-phenithin experimental group with the H-phenithin+inhibitor group, there were statistically significant differences in the above indicators (all P<0.05).

Esculetin alleviates myocardial ischemia-reperfusion injury in rats by activating the JAK2/STAT3 signaling pathway.

This article aimed to explore the targets of the innovative drug HSK31679 in treating metabolic dysfunction-associated steatohepatitis (MASH), and to validate the changes in drug efficacy before and after target knockout through in vivo experiments.

Using the drug and disease databases, HSK31679 and MASH related targets were identified. The core targets were further determined by Cytoscape software. Auto Dock predicted the binding affinity of corresponding proteins to HSK31679. MASH mouse models of wild-type and liver caspase 8 (CASP8) knockout were constructed. Mice were divided into control group (normal feeding of mice + 0.5 mL saline administration), model group (modeling of mice + 0.5 mL saline administration), experimental group (modeling of mice + 3 mg·kg^-1 HSK31679 administration), ΔCASP8 model group (modeling of CASP8 knockout mice + 0.5 mL saline administration) and ΔCASP8 experimental group (modeling of CASP8 knockout mice + 3 mg·kg^-1 HSK31679 administration), with 8 mice in each group. Serum biochemical indicators were measured using an enzyme-linked immunosorbent assay (ELISA) after treatment, and liver sections were stained with HE to velidate the role of core targets of HSK31679′s treatment of MASH.

HE staining revealed significant and typical MASH-associated cellular damage in hepatocytes of the model group, indicating successful model establishment. Five major core targets associated with both HSK31679 and MASH were identified, and HSK31679 exhibited favorable binding activity with the CASP8 protein among them. In animal experiments, the serum triglyceride (TG) levels in the blank group, model group, experimental group, ΔCASP8 model group, and ΔCASP8 experimental group were (0.61±0.05), (1.01±0.15), (0.66±0.13), (0.62±0.09), and (0.63±0.12) mmol·L^-1, respectively; the total cholesterol (TC) levels were (1.24±0.13), (2.88±0.32), (1.60±0.29), (1.30±0.35), and (1.32±0.10) mmol·L^-1, respectively; the alanine aminotransferase (ALT) levels were (74.64±9.31), (140.20±23.74), (88.67±13.67), (78.18±17.66), and (73.58±16.15) IU·L^-1, respectively; the aspartate aminotransferase (AST) levels were (106.33±26.77), (227.32±20.51), (124.58±13.63), (138.37±18.08), and (115.54±27.14) IU·L^-1, respectively. Compared with the model group, the differences of above indicators in the experimental group were all statistically significant (all P<0.01). In HE staining, hepatocytes were arranged in a relatively orderly and dense manner, with a significant reduction in cytoplasmic vacuoles. The aforementioned indicators in the ΔCASP8 experimental group showed no statistically significant differences compared to the ΔCASP8 model group (all P>0.05). There was also no significant difference in the degree of hepatocyte degeneration between the two groups.

CASP8 protein is the key target of HSK31679 in the treatment of MASH. HSK31679 alleviated MASH-related hepatic inflammatory symptoms by binding to CASP8 protein and reducing its activity.

To clarify the role of acyl-CoA thioesterase 8 (ACOT8) across cancers, particularly its prognostic value, and its links to ferroptosis and the immune microenvironment in prostate cancer (PCa).

Using data from The Cancer Genome Atlas (TCGA), R software was used to analyze the gene differential expression of ACOT8 in pan-cancer and the correlation between prognosis. The single sample gene set enrichment analysis (ssGSEA), cell-type identification by estimating relative subsets of known RNA transcripts (CIBERSORT) and tumor immune dysfunction and exclusion (TIDE) algorithms were employed to assess correlations with ferroptosis and immune cell infiltration.

ACOT8 was upregulated in 11 cancers and high expression predicted poor survival, most significantly in PCa. In PCa, ACOT8 expression was negatively correlated with ferroptosis activity and positively correlated with immunosuppressive cells.

ACOT8 is a poor prognostic marker in PCa, potentially by inhibiting ferroptosis and promoting an immunosuppressive microenvironment.

To establish a colloidal gold immunochromatographic method for the rapid detection of cotinine in urines.

To prepare the colloidal gold-labeled antibody probe, optimization of the pH value and the amount of antibody labeling (COT-Mab) was carried out. Following this, the coating concentrations of the cotinine antibody (COT-BSA) for the test (T) line and the sheep anti-mouse immunoglobulin G (IgG) for the control (C) line were also optimized. Subsequently, a colloidal gold immunochromatographic strip was assembled. Finally, the sensitivity of the strip was evaluated.

The optimal conditions established for the colloidal gold immunochromatographic strip were as followings, pH value of 6.5, COT-Mab concentration of 10.00 μg·mL^-1, COT-BSA concentration of 0.10 mg·mL^-1, and sheep anti-mouse IgG concentration of 1.00 mg·mL^-1. The visual detection limit and the cut-off value were 0.01 and 0.20 μg·mL^-1, respectively. Within 15 minutes, this method enabled qualitative analysis of cotinine in urines.

The method has good specificity and accuracy, as well as convenient operation and excellent reproducibility, which can be used for on-site detection and rapid initial screening of smokers and non-smokers during drug clinical trials.

To provide anticoagulation recommendations and optimize pharmacotherapy for a patient with lower extremity arterial embolism following aortic valve replacement by integrating pharmacogenomics and drug-drug interactions with medication education.

A clinical pharmacist participated in the anticoagulation therapy and medication monitoring for a patient who underwent emergency surgery due to lower extremity arterial embolism after mechanical aortic valve replacement. Based on an analysis of the patient′s individual condition and clinical characteristics, and with reference to guidelines and evidence-based literature, the clinical pharmacist guided the perioperative anticoagulation regimen. Factors influencing the effect of warfarin were also analyzed to optimize its dosage.

The patient′s lower extremity arterial embolism improved, and the patient was discharged with favorable follow-up outcomes.

This case provides a reference for clinical pharmacists in managing anticoagulation therapy for patients with lower extremity arterial embolism after mechanical heart valve replacement.

In the context of "internet plus health care", the annual internet outpatient prescriptions of a tertiary children′s hospital (Beijing Children′s Hospital affiliated to Capital Medical University, hereinafter referred to as the hospital) were taken as the objects, and the rationality of prescriptions was analyzed based on the rational drug use system, and the types, causes and drug characteristics of unreasonable treatments were identified to provide data support for the rational drug use management of pediatric Internet outpatient.

All prescriptions from the hospital′s internet outpatient hospital information system (HIS) in 2024 were collected and summarized. Review results were obtained by relying on the Puhua Hecheng Rational Drug Use System, and true positive irrational prescriptions were determined by combining with pharmacists′ manual re-evaluation. Statistical analysis was performed using Excel software.

A total of 58 560 internet outpatient prescriptions were included. The rational drug use software reviewed 1 334 machine-screened positive irrational prescriptions, and 438 true-positive irrational prescriptions were confirmed after manual re-evaluation, with an overall irrational rate of 0.75%. Among the 438 prescriptions, 93.61% involved only one irrational drug item, and a total of 559 medication problems were detected. Among these, inappropriate indication accounted for the highest proportion (63.51%), which was identified as the primary factor by Pareto analysis. Among the problems of inappropriate dosage and usage, 80.22% involved two combined issues (primarily single-dose overdose and daily-dose overdose, accounting for 61.54%). Inappropriate administration route was mainly attributed to non-standard labeling of "as needed" (70.00%), primarily involving nebulized drugs and nutritional supplements. The top three medications involved in irrational prescriptions were all nutritional supplements and vitamins, with this category ranking first among medication classifications.

The overall rationality of prescriptions in the hospital's pediatric internet-based outpatient service is relatively high. However, inappropriate indications and non-standard dosage and usage remain core issues. Targeted optimization of rational drug use system rules, enhanced pharmaceutical intervention, strengthened physician training, and improved remote consultation processes are needed to enhance medication safety and achieve continuous improvement.