OBJECTIVES: To investigate the role and mechanism of Brahma-related gene 1 (Brg1) in regulating the Wnt/β-catenin signaling pathway in a bronchopulmonary dysplasia (BPD) model. METHODS: Wild-type C57BL/6 and Brg1^f1/f1 mice were randomly divided into four groups: wild-type control, wild-type BPD, Brg1^f1/f1 control, and Brg1^f1/f1 BPD (n=5 each). Immortalized mouse pulmonary alveolar type 2 cells (imPAC2) were cultured, and Brg1 gene was knocked down using lentivirus transfection technology. Cells were divided into three groups: control, empty vector, and Brg1 knockdown. Hematoxylin and eosin staining and immunofluorescence were used to detect pathological changes in mouse lung tissue. Western blot and real-time fluorescent quantitative PCR were used to measure Brg1 protein and mRNA expression levels in mouse lung tissue. Western blot and immunofluorescence were used to detect the expression of homeodomain-containing protein homeobox (HOPX), surfactant protein C (SPC), and Wnt/β-catenin signaling pathway proteins in mouse lung tissue and imPAC2 cells. The CCK8 assay was used to assess the proliferation of imPAC2 cells, and co-immunoprecipitation was performed to verify the interaction between Brg1 and β-catenin proteins in imPAC2 cells. RESULTS: Compared to the Brg1^f1/f1 control group and wild-type BPD group, the Brg1^f1/f1 BPD group showed increased alveolar diameter and SPC protein expression, and decreased relative density of pulmonary vasculature and HOPX protein expression (P<0.05). Compared to the control group, the Brg1 knockdown group showed increased cell proliferation ability, protein expression levels of SPC, Wnt5a and β-catenin, and β-catenin protein fluorescence intensity, along with decreased HOPX protein expression (P<0.05). An interaction between Brg1 and β-catenin proteins was confirmed. CONCLUSIONS The Brg1 gene may promote the proliferation of alveolar type 2 epithelial cells by regulating the Wnt/β-catenin signaling pathway, thus influencing the occurrence and development of BPD.
Animals ; DNA Helicases/genetics* ; Transcription Factors/genetics* ; Wnt Signaling Pathway/physiology* ; Nuclear Proteins/genetics* ; Mice ; Bronchopulmonary Dysplasia/etiology* ; Mice, Inbred C57BL ; beta Catenin/physiology* ; Disease Models, Animal ; Cell Proliferation ; Lung/pathology* ; Male

OBJECTIVES: Osteoarthritis (OA) and sarcopenia are significant health concerns in the elderly, substantially impacting their daily activities and quality of life. However, the relationship between them remains poorly understood. This study aims to uncover common biomarkers and pathways associated with both OA and sarcopenia. METHODS: Gene expression profiles related to OA and sarcopenia were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between disease and control groups were identified using R software. Common DEGs were extracted via Venn diagram analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to identify biological processes and pathways associated with shared DEGs. Protein-protein interaction (PPI) networks were constructed, and candidate hub genes were ranked using the maximal clique centrality (MCC) algorithm. Further validation of hub gene expression was performed using 2 independent datasets. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of key genes for OA and sarcopenia. Mouse models of OA and sarcopenia were established. Hematoxylin-eosin and Safranin O/Fast Green staining were used to validate the OA model. The sarcopenia model was validated via rotarod testing and quadriceps muscle mass measurement. Real-time reverse transcription PCR (real-time RT-PCR) was employed to assess the mRNA expression levels of candidate key genes in both models. Gene set enrichment analysis (GSEA) was conducted to identify pathways associated with the selected shared key genes in both diseases. RESULTS: A total of 89 common DEGs were identified in the gene expression profiles of OA and sarcopenia, including 76 upregulated and 13 downregulated genes. These 89 DEGs were significantly enriched in protein digestion and absorption, the PI3K-Akt signaling pathway, and extracellular matrix-receptor interaction. PPI network analysis and MCC algorithm analysis of the 89 common DEGs identified the top 17 candidate hub genes. Based on the differential expression analysis of these 17 candidate hub genes in the validation datasets, AEBP1 and COL8A2 were ultimately selected as the common key genes for both diseases, both of which showed a significant upregulation trend in the disease groups (all P<0.05). The value of area under the curve (AUC) for AEBP1 and COL8A2 in the OA and sarcopenia datasets were all greater than 0.7, indicating that both genes have potential value in predicting OA and sarcopenia. Real-time RT-PCR results showed that the mRNA expression levels of AEBP1 and COL8A2 were significantly upregulated in the disease groups (all P<0.05), consistent with the results observed in the bioinformatics analysis. GSEA revealed that AEBP1 and COL8A2 were closely related to extracellular matrix-receptor interaction, ribosome, and oxidative phosphorylation in OA and sarcopenia. CONCLUSIONS AEBP1 and COL8A2 have the potential to serve as common biomarkers for OA and sarcopenia. The extracellular matrix-receptor interaction pathway may represent a potential target for the prevention and treatment of both OA and sarcopenia.
Sarcopenia/genetics* ; Osteoarthritis/genetics* ; Computational Biology/methods* ; Humans ; Protein Interaction Maps/genetics* ; Animals ; Mice ; Gene Expression Profiling ; Gene Ontology ; Transcriptome ; Male ; Signal Transduction/genetics* ; Gene Regulatory Networks

OBJECTIVES: Osteoarthritis (OA) is one of the most common chronic degenerative diseases, with chondrocyte apoptosis and extracellular matrix (ECM) degradation as the major pathological changes. The mechanical stimulation can attenuate chondrocyte apoptosis and promote ECM synthesis, but the underlying molecular mechanisms remain unclear. This study aims to investigate the role of primary cilia (PC) in mediating the effects of mechanical stimulation on OA progression. METHODS: In vivo, conditional knockout mice lacking intraflagellar transport 88 (IFT88^flox/flox IFT88 knockout; i.e., primary cilia-deficient mice) were generated, with wild-type mice as controls. OA models were established via anterior cruciate ligament transection combined with destabilization of the medial meniscus, followed by treadmill exercise intervention. OA progression was evaluated by hematoxylin-eosin staining, safranin O-fast green staining, and immunohistochemistry; apoptosis was assessed by TUNEL staining; and limb function by rotarod testing. In vitro, primary articular chondrocytes were isolated from mice and transfected with lentiviral vectors to suppress IFT88 expression, thereby constructing a primary cilia-deficient cell model. Interleukin-1β (IL-1β) was used to induce an inflammatory environment, while cyclic tensile strain (CTS) was applied via a cell stretcher to mimic mechanical loading on chondrocytes. Immunofluorescence and Western blotting were used to detect the protein expression levels of type II collagen α1 chain (COL2A1), primary cilia, IFT88, and caspase-12; reverse transcription polymerase chain reaction was performed to assess COL2A1 mRNA levels; and flow cytometry was used to evaluate apoptosis. RESULTS: In vivo, treadmill exercise significantly reduced Osteoarthritis Research Society International (OARSI) scores and apoptotic cell rates, and improved balance ability in wild-type OA mice, whereas IFT88-deficient OA mice showed no significant improvement. In vitro, CTS inhibited IL-1β-induced ECM degradation and apoptosis in primary chondrocytes; however, this protective effect was abolished in cells with suppressed primary cilia expression. CONCLUSIONS Mechanical stimulation delays OA progression by mediating signal transduction through primary cilia, thereby inhibiting cartilage degeneration and chondrocyte apoptosis.
Animals ; Chondrocytes/cytology* ; Apoptosis/physiology* ; Mice ; Cilia/metabolism* ; Osteoarthritis/pathology* ; Extracellular Matrix/metabolism* ; Mice, Knockout ; Disease Progression ; Interleukin-1beta ; Male ; Cells, Cultured

Objective:To investigate the clinical value of changes in serum total cholesterol (TC), chitinase protein-40 (YKL-40), and B7 homolog 4 (B7-H4) levels in patients with severe acute pancreatitis (SAP) complicated with abdominal compartment syndrome (ACS).Methods:A total of 388 SAP patients admitted to the First Affiliated Hospital of Xi'an Medical College from January 2022 to May 2024 were selected as the study group. They were grouped into the ACS group (227 cases) and a non-ACS group (161 cases) based on whether they had concurrent ACS. Another 215 individuals who underwent health check up were selected as the control group. Enzyme linked immunosorbent assay (ELISA) was applied to detect serum levels of TC, YKL-40, and B7-H4. Spearman test was applied to analyze the correlation between serum TC, YKL-40, B7-H4 levels and Acute Physiology and Chronic Health Status Scoring System Ⅱ(APACHE Ⅱ) score and intra-abdominal pressure (IAP)value. Multivariate Logistic regression was applied to analyze the influencing factors of SAP patients complicated ACS. The receiver operating characteristic (ROC) curve was applied to analyze the clinical diagnostic value of serum TC, YKL-40, B7-H4 levels in SAP patientscomplicated with ACS.Results:The serum levels of TC, YKL-40, and B7-H4 in the study group were higher than those in the control group : (5.79 ± 0.81) mmol/L vs. (4.67 ± 0.57) mmol/L, (49.46 ± 7.51) μg/L vs. (36.82 ± 5.93) μg/L, (63.66 ± 11.23) μg/L vs. (52.85 ± 9.21) μg/L, there were statistical differences ( P<0.05). The results of single factor analysis showed that time of stay in intensive care unit (ICU), C-reactive protein (CRP), white blood cell count (WBC), blood amylase (AMY), APACHEⅡ score, IAP value, serum TC, YKL-40, B7-H4 levels and heart rate were the risk factors for ACS in SAP patients ( P<0.05). The results of correlation analysis showed that the levels of serum TC, YKL-40 and B7-H4 were positively correlated with APACHEⅡ score and IAP value (the r value were 0.459, 0.511, 0.445 and 0.742, 0.794, 0.761, P<0.05). Multivariate Logistic regression analysis showed that time of stay in ICU, APACHE Ⅱ score, IAP value and high levels of serum TC, YKL-40 and B7-H4 were independent risk factors for ACS in SAP patients ( P<0.05). ROC curve analysis results showed that the area under the curve(IUC) of serum TC, YKL-40 and B7-H4 predicted SAP patients with ACS was 0.868. Conclusions:The levels of serum TC, YKL-40, and B7-H4 are higher in patients with SAP complicated with ACS, and their combined detection has better clinical value for SAP complicated with ACS patients.

Objective To translate Evidence-Informed Decision-Making Competence Measure for Chinese nurses and test its validity and reliability.Methods A research group was set up to use the Brislin translation model to translate the original scale into Chinese,and the back translation,cross-cultural adaptation,pre-experiment and cognitive interview were conducted to finally form the Chinese version of the Evidence-Informed Decision-Making Competence Measure for nurses.A total of 1 247 nurses from 7 tertiary A hospitals in Beijing,Hubei,Hunan and Xinjiang were selected by convenience sampling method in April 2024 to test its reliability and validity.Results 1 026 effective question-naires were collected,with an effective recovery rate of 82.28％.The Chinese version of the Evidence-Informed Decision-Making Competence Measure included 25 items,including knowledge/skill,attitude and behavior.A total of 3 common factors were extracted from exploratory factor analysis,and the cumulative variance contribution rate was 91.725％.The content validity index at the item level was 0.83-1.00;the content validity index at the scale level was 0.988;the calibration association validity was 0.496.The Cronbach's α coefficient of the whole scale was 0.992;the half-point reliability was 0.930;the retest reliability was 0.927.Conclusion The Chinese version of Evidence-Informed Decision-Making Competence Measure for nurses has good reliability and validity,and it can be used to evaluate the evidence-informed decision-making competence of Chinese nurses,provide references for promoting evidence-based nursing practice and evidence-informed decision-making.

Objective To explore the pathophysiological molecular mechanism of the up-regulation of CircPDS5B level involved in premature birth.Methods The placental tissues of full-term infants(Group 1,gestational age≥37 weeks),late premature infants(Group 2,34 weeks≤gestational age<37 weeks),premature infants(Group 3,32 weeks

Immunometabolism studies focus on the relationships between immune cell functions and cellular energy metabolism pathways.Immunometabolism plays an important regulatory role in immune-related diseases.Mycobacterium tuberculosis(M.tb),an important intracellular pathogenic bacterium,enters alveolar macrophages after infection.The confrontation between M.tb and the host is a complex and dynamic process involving multiple aspects and mechanisms,such as the immune response,granuloma formation,and immune evasion.M.tb effector proteins play key roles in maintaining bacterial virulence and regulating host cell metabolism.This article reviews the reprogramming process of glucose metabolism,lipid metabolism,and immunometabolism,as well as changes in mi-tochondrial function in M.tb-infected host cells,thereby revealing the relationship between M.tb pathogenicity and host metabolic regu-lation,which is important for understanding tuberculosis.

OBJECTIVE: Observational studies have found associations between inflammatory bowel disease (IBD) and the risk of dementia, including Alzheimer's dementia (AD) and vascular dementia (VD); however, these findings are inconsistent. It remains unclear whether these associations are causal. METHODS: We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and dementia. Mendelian randomization (MR) analysis based on summary genome-wide association studies (GWASs) was performed. Genetic correlation and Bayesian co-localization analyses were used to provide robust genetic evidence. RESULTS: Ten observational studies involving 80,565,688 participants were included in this meta-analysis. IBD was significantly associated with dementia (risk ratio [ RR] =1.36, 95% CI = 1.04-1.78; I ² = 84.8%) and VD ( RR = 2.60, 95% CI = 1.18-5.70; only one study), but not with AD ( RR = 2.00, 95% CI = 0.96-4.13; I ² = 99.8%). MR analyses did not supported significant causal associations of IBD with dementia (dementia: odds ratio [ OR] = 1.01, 95% CI = 0.98-1.03; AD: OR = 0.98, 95% CI = 0.95-1.01; VD: OR = 1.02, 95% CI = 0.97-1.07). In addition, genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and dementia. CONCLUSION Our study did not provide genetic evidence for a causal association between IBD and dementia risk. The increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.
Humans ; Mendelian Randomization Analysis ; Inflammatory Bowel Diseases/complications* ; Dementia/etiology* ; Observational Studies as Topic ; Genome-Wide Association Study

Objective:To investigate the value of triglyceride glucose index(TyG)and monocyte to high-density lipoprotein choles-terol ratio(MHR)in the diagnosis of acute exacerbation of chronic obstructive pulmonary disease(AECOPD)complicated by heart fail-ure(HF),as well as the correlation of TyG and MHR with cardiac function in AECOPD patients.Methods:A retrospective analysis was performed for the clinical data of 298 AECOPD patients who were admitted to The First Hospital of Lanzhou University from January 2020 to December 2021,and according to the clinical manifestation,B-type natriuretic peptide/N-terminal B-type natriuretic peptide precursor,and echocardiography,the 298 AECOPD patients were divided into HF group with 127 patients and non-HF group with 171 patients.Related clinical indicators were compared between the two groups,and a regression analysis was used to identify the pos-sible risk factors for HF in AECOPD patients.The receiver operat-ing characteristic(ROC)curve analysis was used to investigate the value of TyG and MHR alone or in combination in the diagnosis of AECOPD complicated by HF,and a correlation analysis was used to investigate the correlation of TyG and MHR with cardiac function parameters(ejection fraction,ventricular wall thickness,cardiac chamber size,and valve regurgitation velocity)and pulmonary artery pressure in AECOPD patients.Results:The binary logistic regres-sion analysis showed that fasting blood glucose,absolute monocyte count,high-density lipoprotein cholesterol(HDL-C),arrhythmia,TyG,and MHR were independent risk factors for HF in AECOPD patients,and the HF group had significantly higher levels of TyG and MHR than the non-HF group(P<0.001).TyG had an area under the ROC curve(AUC)of 0.805(95%CI=0.754-0.856,P<0.001)in the diagnosis of AECOPD complicated by HF,and MHR had an AUC of 0.762(95%CI=0.707-0.817,P<0.001),while TyG combined with MHR had an AUC of 0.870(95%CI=0.828-0.912,P<0.001).The correlation analysis showed that TyG was negatively correlated with left ventricular ejection fraction and left ventricular fractional shortening and was positively correlated with end-diastolic interven-tricular septal thickness,mitral regurgitation velocity,and left ventricular end-diastolic posterior wall thickness,while MHR was nega-tively correlated with left ventricular stroke volume and left ventricular fractional shortening and was positively correlated with end-diastolic interventricular septal thickness,right ventricular anteroposterior diameter,right ventricular superior-inferior diameter,right ventricular transverse diameter,tricuspid regurgitation velocity,left ventricular end-diastolic posterior wall thickness,and pulmonary artery pressure.Conclusion:Fasting blood glucose,absolute monocyte count,HDL-C,arrhythmia,TyG,and MHR are independent risk factors for AECOPD complicated by HF.Both TyG and MHR have a certain value in the diagnosis of HF,and the combination of TyG and MHR has a better efficacy than each indicator alone in the diagnosis of AECOPD complicated by HF.TyG is correlated with the cardiac function parameters such as left ventricular ejection fraction,ventricular wall thickness,and mitral regurgitation velocity in patients with AECOPD and may have a stronger correlation with the left ventricle;MHR is correlated with right ventricular chamber size,tricuspid regurgitation velocity,and pulmonary artery pressure and may have a stronger correlation with the right ventricle.

A novel analytical method was developed in this study by combining online solid phase extraction with ultra performance liquid chromatography-tandem mass spectrometry(Online SPE-UPLC-MS/MS)for simultaneous determination of 50 kinds of steroid hormones in surface water.Specifically,after high-speed centrifugation of 4 mL water samples,the supernatant was directly injected into an Oasis HLB online SPE column for enrichment and purification.Subsequently,the target compounds were transferred to the analytical column via valve switching for separation and analysis.The chromatographic separation was performed on a Thermo Acclaim RSLC C18 column(100 mm×2.1 mm,2.2 μm),using a mobile phase composed of 5 mmol/L ammonium fluoride aqueous solution and acetonitrile.Mass spectrometric detection was conducted in positive ion mode,utilizing multiple reaction monitoring(MRM)with quantification achieved by the internal standard method.The method validation demonstrated that the limits of detection(LOD)for the 50 kinds of steroid hormones ranged from 0.02 to 0.50 ng/L,while the limits of quantification(LOQ)were between 0.08 and 1.67 ng/L.The average recoveries in surface water samples at spiked concentrations of 5,20 and 200 ng/L were between 74.1％and 119％,with relative standard deviations(RSDs)of 0.2％to 9.9％.This method was applied to analyze 11 surface water samples collected from sites surrounding a pharmaceutical and chemical industrial park.A total of 44 kinds of steroid hormones were detected,with concentrations ranging from 0.11 to 88.6 ng/L,revealing the presence of hormone contamination in the environmental waters surrounding industrial areas.Compared with the traditional offline SPE methods,the proposed online SPE technique significantly reduced sample volume requirements and pretreatment time,while minimizing the loss of target compounds during the pretreatment process.Moreover,compared to reported online SPE techniques,this method achieved high-throughput analysis of multiple classes of steroid hormones,with lower detection limits and higher recoveries.Overall,this method provided rapid sample preparation,high sensitivity,and excellent stability,making it suitable for the direct analysis of trace steroid hormones in surface water.