ObjectiveTo investigate the mechanisms of Tongnao decoction （TND） in mice with acute ischemic stroke （AIS）. MethodsFifty male C57BL/6J mice were randomly divided into a sham operation group， model group， TND low-dose group （1.86 g·kg^-1）， TND high-dose group （3.72 g·kg^-1）， and butylphthalide （NBP） group （10 mg·kg^-1）， with 10 mice in each group. A mouse model of cerebral ischemic injury was established using photochemical thrombosis （PT）. The sham operation group and model group were administered an equal volume of normal saline by gavage. All five groups were treated once daily for 14 consecutive days. Behavioral tests were performed before modeling and at the end of administration. T₂-weighted imaging （T₂WI） was performed 3 days after modeling to evaluate the extent of injury. Hematoxylin-eosin （HE） staining was used to observe histological changes in the cerebral cortex， and Nissl staining was used to observe neuronal morphology. Cerebral blood flow in mice was detected using a laser speckle contrast imaging （LSCI） system. Immunofluorescence staining was used to detect the cell proliferation marker bromodeoxyuridine （BrdU） and the highly glycosylated type I transmembrane glycoprotein CD34. Western blot analysis was used to detect the expression levels of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， glycogen synthase kinase-3β （GSK-3β）， and their phosphorylation levels， as well as tight junction-related proteins zonula occludens-1 （ZO-1）， Occludin， and Claudin-5 in the peri-infarct tissue. Thirty-five zebrafish were randomly divided into normal control group， model group， TND low and high dose groups （0.16， 0.32 g·L^-1） and NBP group （10 μmol·L^-1）， with 7 in each group. A stereoscopic fluorescence microscope was used to observe vascular growth in zebrafish. ResultsImaging showed that PT caused ischemia in the right cortical region. Behavioral tests indicated that， compared with the model group， the drug-treated groups reduced the error rate of irregular balance ladder climbing on the affected side and shortened the tape removal time （P<0.05）. HE staining and Nissl staining showed that， compared with the model group， the drug-treated groups exhibited reduced brain tissue damage， fewer scars， and improved neuronal morphology. LSCI results showed that the drug-treated groups partially restored cerebral blood perfusion and promoted the establishment of collateral circulation compared with the model group. Immunofluorescence staining indicated that the drug-treated groups increased the positive rates of BrdU and CD34 compared with the model group （P<0.01）， promoting angiogenesis. Meanwhile， compared with the model group， the drug-treated groups upregulated the expression levels of p-PI3K， p-Akt， p-GSK-3β， and tight junction proteins ZO-1， Occludin， and Claudin-5 （P<0.05，P<0.01）， and increased the number of intersegmental vessels in zebrafish （P<0.05，P<0.01）. ConclusionTND can promote angiogenesis around the infarct in PT model mice by regulating the PI3K/Akt/GSK-3β signaling pathway， thereby improving cerebral ischemic injury.

Objective To explore the prognostic value of glycolysis-related genes in colorectal cancer (CRC) patients and formulate a novel glycolysis-related prognostic risk model. Methods Single-cell and bulk transcriptomic data of CRC patients, along with clinical information, were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Glycolysis scores for each sample were calculated using single-sample Gene Set Enrichment Analysis (ssGSEA). Kaplan-Meier survival curves were generated to analyze the relationship between glycolysis scores and overall survival. Novel glycolysis-related subgroups were defined among the cell type with the highest glycolysis scores. Gene enrichment analysis, metabolic activity assessment, and univariate Cox regression were performed to explore the biological functions and prognostic impact of these subgroups. A prognostic risk model was built and validated based on genes significantly affecting the prognosis. Gene Set Enrichment Analysis (GSEA) was conducted to explore differences in biological processes between high- and low-risk groups. Differences in immune microenvironment and drug sensitivity between these groups were assessed using R packages. Potential targeted agents for prognostic risk genes were predicted using the Enrichr database. Results Tumor tissues showed significantly higher glycolysis scores than normal tissues, which was associated with a poor prognosis in CRC patients. The highest glycolysis score was observed in epithelial cells, within which we defined eight novel glycolysis-related cell subpopulations. Specifically, the P4HA1⁺ epithelial cell subpopulation was associated with a poor prognosis. Based on signature genes of this subpopulation, a six-gene prognostic risk model was formulated. GSEA revealed significant biological differences between high- and low-risk groups. Immune microenvironment analysis demonstrated that the high-risk group had increased infiltration of macrophages and tumor-associated fibroblasts, along with evident immune exclusion and suppression, while the low-risk group exhibited higher levels of B cell and T cell infiltration. Drug sensitivity analysis indicated that high-risk patients were more sensitive to Abiraterone, while low-risk patients responded to Cisplatin. Additionally, Valproic acid was predicted as a potential targeted agent. Conclusion High glycolytic activity is associated with a poor prognosis in CRC patients. The novel glycolysis-related prognostic risk model formulated in this study offers significant potential for enhancing the diagnosis and treatment of CRC.
Humans ; Colorectal Neoplasms/pathology* ; Glycolysis/genetics* ; Prognosis ; Transcriptome ; Tumor Microenvironment/genetics* ; Gene Expression Profiling ; Single-Cell Analysis ; Gene Expression Regulation, Neoplastic ; Male ; Female ; Kaplan-Meier Estimate

AIM:The current study aims to investigate the protective effect of farrerol against sepsis-induced cardiomyopathy and its mechanisms in mice.METHODS:Eighteen male C57BL/6 mice were randomly divided into the control,lipopolysaccharide(LPS;10 mg/kg),and LPS+farrerol(40 mg/kg)groups,with 6 mice in each group.The car-diac function of the mice was assessed via ultrasonography.Myocardial pathological changes and mitochondrial damage were examined via hematoxylin and eosin staining and transmission electron microscopy,respectively.TUNEL staining was performed to evaluate myocardial apoptosis,and RT-qPCR and ELISA were conducted to assess cardiac tissue inflam-matory factor mRNA expression and the serum inflammatory factor levels.Furthermore,the malondialdehyde(MDA),glutathione(GSH),superoxide dismutase(SOD),Fe2+,and reactive oxygen species(ROS)levels in the myocardial tis-sues were evaluated using kits and immunofluorescence.Western blot analysis was performed to investigate the levels of key proteins associated with apoptosis,ferroptosis,and the nuclear factor E2-related facor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway.RESULTS:Farrerol pretreatment prevented the reduction of cardiac function in mice with SIC(P<0.01).Further,it decreased myocardial tissue pathological damage,mitochondrial ultrastructural disruption,the inflammatory factor levels(P<0.01),cardiac oxidative stress and Fe2+content(P<0.01),the expression of apoptotic cardiomyocytes(P<0.01),and the level of Bax expression(P<0.01).Finally,it increased the protein expression of Bcl-2,glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),Nrf2,and HO-1(P<0.05 or P<0.01).The control,LPS,and LPS+farrerol groups did not significantly differ in terms of left ventricular anterior wall end-diastolic depth and left ventricular posterior wall end-diastolic depth(P>0.05).CONCLUSION:Farrerol reduces LPS-induced septic myocardial injury and inhibits the development of ferroptosis in the myocardial tissues of mice,which may be related to the Nrf2/HO-1 signaling pathway.

Objective:To explore the gaze characteristics towards emotional portraits in children with attention deficit hyperactivity disorder(ADHD),in order to reveal their potential unique patterns of emotional cognition.Methods:A case-control design was employed,including 81 children diagnosed with the DSM-5 ADHD and 57 normal control(NC)children.Emotional images from the Chinese Children's Emotional Image Library were used as stimuli.The Tobii Pro X3-120 eye-tracking device was utilized to record fixation count(FC)and fixation duration percentage(FDP)under a free-viewing paradigm.Mixed-effects ANOVA was applied to explore the effects of group,gaze region(eyes and mouth),and emotional attributes on gaze characteristics,controlling for gen-der and age.Results:The FC and FDP of ADHD children were lower than those of NC children,particularly in the eye region of non-negative emotional images(P＜0.05).However,no significant differences were observed be-tween the two groups when viewing negative emotional images(sadness and anger)(P＞0.05).NC children ex-hibited a significant emotional bias effect in their gaze behavior towards emotional portraits(P＜0.05),whereas ADHD group showed only slight differences between non-negative emotional images(adjusted P＜0.05),indica-ting a weaker overall emotional attention bias.Conclusion:Children with ADHD display reduced attention to non-negative emotional expressions and a diminished emotional attention bias,suggesting potential deficits in emotional processing during face perception.

Objective:To explore the gaze characteristics towards emotional portraits in children with attention deficit hyperactivity disorder(ADHD),in order to reveal their potential unique patterns of emotional cognition.Methods:A case-control design was employed,including 81 children diagnosed with the DSM-5 ADHD and 57 normal control(NC)children.Emotional images from the Chinese Children's Emotional Image Library were used as stimuli.The Tobii Pro X3-120 eye-tracking device was utilized to record fixation count(FC)and fixation duration percentage(FDP)under a free-viewing paradigm.Mixed-effects ANOVA was applied to explore the effects of group,gaze region(eyes and mouth),and emotional attributes on gaze characteristics,controlling for gen-der and age.Results:The FC and FDP of ADHD children were lower than those of NC children,particularly in the eye region of non-negative emotional images(P＜0.05).However,no significant differences were observed be-tween the two groups when viewing negative emotional images(sadness and anger)(P＞0.05).NC children ex-hibited a significant emotional bias effect in their gaze behavior towards emotional portraits(P＜0.05),whereas ADHD group showed only slight differences between non-negative emotional images(adjusted P＜0.05),indica-ting a weaker overall emotional attention bias.Conclusion:Children with ADHD display reduced attention to non-negative emotional expressions and a diminished emotional attention bias,suggesting potential deficits in emotional processing during face perception.

AIM:The current study aims to investigate the protective effect of farrerol against sepsis-induced cardiomyopathy and its mechanisms in mice.METHODS:Eighteen male C57BL/6 mice were randomly divided into the control,lipopolysaccharide(LPS;10 mg/kg),and LPS+farrerol(40 mg/kg)groups,with 6 mice in each group.The car-diac function of the mice was assessed via ultrasonography.Myocardial pathological changes and mitochondrial damage were examined via hematoxylin and eosin staining and transmission electron microscopy,respectively.TUNEL staining was performed to evaluate myocardial apoptosis,and RT-qPCR and ELISA were conducted to assess cardiac tissue inflam-matory factor mRNA expression and the serum inflammatory factor levels.Furthermore,the malondialdehyde(MDA),glutathione(GSH),superoxide dismutase(SOD),Fe2+,and reactive oxygen species(ROS)levels in the myocardial tis-sues were evaluated using kits and immunofluorescence.Western blot analysis was performed to investigate the levels of key proteins associated with apoptosis,ferroptosis,and the nuclear factor E2-related facor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway.RESULTS:Farrerol pretreatment prevented the reduction of cardiac function in mice with SIC(P<0.01).Further,it decreased myocardial tissue pathological damage,mitochondrial ultrastructural disruption,the inflammatory factor levels(P<0.01),cardiac oxidative stress and Fe2+content(P<0.01),the expression of apoptotic cardiomyocytes(P<0.01),and the level of Bax expression(P<0.01).Finally,it increased the protein expression of Bcl-2,glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),Nrf2,and HO-1(P<0.05 or P<0.01).The control,LPS,and LPS+farrerol groups did not significantly differ in terms of left ventricular anterior wall end-diastolic depth and left ventricular posterior wall end-diastolic depth(P>0.05).CONCLUSION:Farrerol reduces LPS-induced septic myocardial injury and inhibits the development of ferroptosis in the myocardial tissues of mice,which may be related to the Nrf2/HO-1 signaling pathway.

Objective To develop measurement instruments of dynamic capabilities for public hospitals,providing a reference for the evaluation and enhancement of their dynamic capabilities.Methods The initial construction of the measurement instruments of dynamic capabilities for public hospitals was based on literature review and focused group discussions.Two rounds of expert consultation were conducted using the Delphi method,and the reliability and validity of the questionnaire was initially examined through pre-survey.Results The effective response rates for both rounds of consultation were above 85％,with high positive coefficient,the authority coefficients greater than 0.8,and variation coefficients less than 0.25,indicating a high level of consensus among experts.Furthermore,the reliability and validity are acceptable.After integrating expert feedback,the measurement instruments of dynamic capabilities for public hospitals were finalized,encompassing four dimensions:sensing,learning,integration capability,and innovation capabilities.Conclusion The measurement instruments of dynamic capabilities for public hospitals,developed based on the Delphi method,can be applied in the practice of evaluating and enhancing the dynamic capabilities of public hospitals.

Objective To develop measurement instruments of dynamic capabilities for public hospitals,providing a reference for the evaluation and enhancement of their dynamic capabilities.Methods The initial construction of the measurement instruments of dynamic capabilities for public hospitals was based on literature review and focused group discussions.Two rounds of expert consultation were conducted using the Delphi method,and the reliability and validity of the questionnaire was initially examined through pre-survey.Results The effective response rates for both rounds of consultation were above 85％,with high positive coefficient,the authority coefficients greater than 0.8,and variation coefficients less than 0.25,indicating a high level of consensus among experts.Furthermore,the reliability and validity are acceptable.After integrating expert feedback,the measurement instruments of dynamic capabilities for public hospitals were finalized,encompassing four dimensions:sensing,learning,integration capability,and innovation capabilities.Conclusion The measurement instruments of dynamic capabilities for public hospitals,developed based on the Delphi method,can be applied in the practice of evaluating and enhancing the dynamic capabilities of public hospitals.