OBJECTIVES: To investigate the role and mechanism of copper overload-mediated endoplasmic reticulum stress (ERS) in vascular endothelial injury in Kawasaki disease (KD). METHODS: Four-week-old male C57BL/6 mice were randomly divided into four groups: control, KD, KD plus copper chelator tetrathiomolybdate (TTM), and KD plus ERS inhibitor AMG PERK 44 (AMG) (n=20 per group). A KD mouse model was established using Candida albicans extract. Human umbilical vein endothelial cells (HUVECs) were divided into control (intervention with healthy children's serum), KD (intervention with KD patients' serum), and KD+TTM (intervention with KD patients' serum plus 20 µmol/L TTM). Copper deposition in mouse heart tissue was assessed using rubeanic acid staining. Vascular pathological changes were observed using hematoxylin-eosin staining and measurement of abdominal aortic diameter and area. ERS activation was detected by transmission electron microscopy and immunofluorescence. HUVEC viability, apoptosis, and functional changes were evaluated using CCK8, flow cytometry, cell scratch assay, and angiogenesis experiments. ERS marker protein expression levels were measured by Western blot. RESULTS: Compared to the KD group, the KD+TTM and KD+AMG groups showed reduced copper deposition in the vascular wall, decreased swelling of coronary endothelial cells and endoplasmic reticulum, reduced inflammatory cell infiltration, and less abdominal aortic lesion expansion. The abdominal aortic diameter and area, and the fluorescence intensity of ERS marker proteins (GRP78 and CHOP) were significantly lower (P<0.05). Compared to the KD group, the KD+TTM group exhibited increased cell viability, tube number, and scratch healing rate, along with decreased apoptosis rate and expression of ERS marker proteins (GRP78, CHOP, ATF6, and p-PERK) (P<0.05). CONCLUSIONS Copper overload aggravates vascular endothelial injury in KD by activating the ERS pathway. TTM can exert protective effects on the endothelium by regulating copper metabolism and inhibiting the ERS pathway.
Endoplasmic Reticulum Stress ; Copper/toxicity* ; Male ; Mucocutaneous Lymph Node Syndrome/metabolism* ; Animals ; Humans ; Endoplasmic Reticulum Chaperone BiP ; Mice, Inbred C57BL ; Mice ; Human Umbilical Vein Endothelial Cells ; Apoptosis ; Endothelium, Vascular/injuries*

OBJECTIVE: To investigate the anti-tumor effects of cinobufacini (CINO) on hepatocellular carcinoma (HCC) induced by des-gamma-carboxy-prothrombin (DCP) and to uncover the underlying mechanisms. METHODS: The inhibitory effect of CINO on HCC cell proliferation was evaluated using the cell counting kit-8 method, and the apoptosis rate was quantified using flow cytometry. Immunofluorescence and Western blot analyses were used to investigate the differential expression of proteins associated with cell growth, apoptosis, migration, and invasion pathways after CINO treatment. The therapeutic potential of CINO for HCC was confirmed, and the possibility of combining cinobufacini with c-Met inhibitor for the treatment of primary HCC was further validated by in vivo experiments. RESULTS: Under the induction of DCP, CINO inhibited the activity of HCC cells, induced apoptosis, and inhibited migration and invasion. Upon the induction of DCP, CINO regulated c-Met activation and the activation of the phosphatidylinositol-3 kinase/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) pathways. In a mouse model of HCC, CINO exhibited significant antitumor effects by inhibiting the phosphorylation of c-Met and the downstream PI3K/AKT and MEK/ERK pathways in tumor tissues. CONCLUSIONS CINO inhibited HCC cell growth, promoted apoptosis, and suppressed HCC cell invasion and migration by targeting c-Met and PI3K/AKT and MEK/ERK signaling pathways under DCP induction.
Carcinoma, Hepatocellular/drug therapy* ; Proto-Oncogene Proteins c-met/metabolism* ; Liver Neoplasms/drug therapy* ; Signal Transduction/drug effects* ; Animals ; Humans ; Cell Movement/drug effects* ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Amphibian Venoms/therapeutic use* ; Cell Line, Tumor ; Neoplasm Metastasis ; Cell Survival/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Neoplasm Invasiveness ; Mice, Inbred BALB C ; Mice, Nude ; Mice ; Male ; Bufanolides/therapeutic use* ; Protein Precursors ; Prothrombin ; Biomarkers

Blood from a case of group B epidemic cerebrospinal meningitis identified in February 2024 in Ganzhou City,Jiangxi Province,and throat swabs from close contacts were collected for isolation and culture.The isolates were subjected to serogrouping,drug sensitivity testing,and whole genome sequencing and analysis,to provide a basis for epidemiological inves-tigation and clinical drug use.One strain of Neisseria meningitidis was isolated from the blood of the case and denoted group B.The MLST type was ST-7962,with no clonal group attribution.The phylogenetic tree showed that it was genetically close to the 1977 Shanghai carrier isolate(id-52231).Drug sensitivity results indicated that the strain was sensitive to 8 drugs:azithro-mycin,cefotaxime,minocycline,ceftriaxone,chloramphenicol,meropenem,rifampicin,and benzylpenicillin;resistant to cot-rimoxazole,levofloxacin,and ciprofloxacin;and showed an intermediate response to penicillin.This report describes the first case of ST-7962 group B meningoencephalitis found in Jiangxi Province.Monitoring of Neisseria meningitidis carriage,drug re-sistance,and molecular characteristics of strains in the healthy population in this region should be strengthened,to provide la-boratory support for the clinical use of medications,traceability,and control of the pathogen underlying meningoencephalitis infection.

The data from outpatient prescriptions of small-size aspirin enteric-coated tablets(25 mg/tablet)in a community hospital were analyzed to provide reference for rational clinical drug use.Patients'medication information of 1 325 prescriptions was collected and analyzed by defined daily dose system(DDDs)and drug utilization index(DUI),and the rationality of drug use was analyzed according to drug instructions and literature.The mean age of males and females were(73.70±8.33)years old and(72.95±8.34)years old,respectively.The top 3 DDDs age groups were women aged 60-79 years,men aged 60-79 years and women aged 80-99 years.The proportion of prescriptions in female patients was 59.62%.DUI ranges from 0.75 to 0.85.Irrational drug use was found in 123 prescriptions,including 89 prescriptions(72.35%)of inappropriate drug selection,19 prescriptions(15.45%)with low dose,6 prescriptions(4.88%)with contraindication,5 prescriptions(4.06%)with inconsistent frequency of administration,2 prescriptions(1.63%)of out-of-indication drug use,and 2 prescriptions(1.63%)of high dose.For the phenomenon of irrational drug use,it is necessary to conduct real-time intervention to ensure the safety and effectiveness of drug use.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

We aimed to explore the value of personalized narrative intervention in the nursing care of elderly patients with stroke hemiplegia(SH).A total of 68 elderly patients with SH were selected and divided into two groups using the ball-rolling method,with 34 cases in each group.The control group received routine nursing care,while the observation group received routine care and personalized narrative nursing.The nursing outcomes of the two groups were compared.Compared with the control group,the observation group had lower scores in anxiety and depression(P<0.05),and higher scores in the Functional Evaluation of Cognitive State-Short Screening(FECS-SS)(P<0.05).The rehabilitation effects of normal rate in the observation group was higher than that in the control group(P<0.05).Personalized narrative nursing for SH patients can effectively relieve the patients'negative emotions,enhance their compliance with rehabilitation,and improve the outcomes of rehabilitation.

The data from outpatient prescriptions of small-size aspirin enteric-coated tablets(25 mg/tablet)in a community hospital were analyzed to provide reference for rational clinical drug use.Patients'medication information of 1 325 prescriptions was collected and analyzed by defined daily dose system(DDDs)and drug utilization index(DUI),and the rationality of drug use was analyzed according to drug instructions and literature.The mean age of males and females were(73.70±8.33)years old and(72.95±8.34)years old,respectively.The top 3 DDDs age groups were women aged 60-79 years,men aged 60-79 years and women aged 80-99 years.The proportion of prescriptions in female patients was 59.62%.DUI ranges from 0.75 to 0.85.Irrational drug use was found in 123 prescriptions,including 89 prescriptions(72.35%)of inappropriate drug selection,19 prescriptions(15.45%)with low dose,6 prescriptions(4.88%)with contraindication,5 prescriptions(4.06%)with inconsistent frequency of administration,2 prescriptions(1.63%)of out-of-indication drug use,and 2 prescriptions(1.63%)of high dose.For the phenomenon of irrational drug use,it is necessary to conduct real-time intervention to ensure the safety and effectiveness of drug use.