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

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 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 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.

Objective To investigate the effect and mechanism of hypoxia inducible factor-1 α/aquaporin-4(HIF-1α/AQP4)pathway in high altitude cerebral edema(HACE)after blood-brain barrier injury in rats.Methods Adult male SD rats(n=40)were randomly divided into two groups:control group(Ctrl,n=20)and high altitude cerebral edema group(HACE,n=20).The rats in the control group were reared in Xining(altitude 2261 m)for 4 days,and the rats in HACE group were reared in low-pressure simulation chamber(altitude 5000 m)for 4 days.Brain water content was measured by the method of dry and wet weight.The intracranial structure,morphology and signal changes of small animals were observed through T2 weighted image of 7.0 T MRI.The morphological changes of neurons and the apoptosis of nerve cells in the CA1 region of hippocampal tissue were observed by the staining of Nissl and TUNEL.Immunohistochemical staining was performed to observe the extravasation of immunoglobulin G(IgG).The expressions of HIF-1α,AQP4,matrix metalloproteinase-9(MMP-9),claudin-5,occludin and zonula occludens-1(ZO-1)in the tissue of hippocampal were detected by the method of Western blotting and immunofluorescent staining.Results The brain water content increased significantly in the HACE group(P＜0.05).The neurons in CA1 region of hippocampal tissue were atrophic and deformed,the arrangement of neurons was disordered in the HACE group.The number of neurons decreased significantly,the apoptosis of nerve cells increased significantly,and the IgG exudates obviously in the CA1 region of hippocampal tissue in the HACE group.The expressions of HIF-1α,AQP4 and MMP-9 proteins increased significantly,while claudin-5,occludin and ZO-1 proteins decreased significantly in the CA1 region of hippocampal tissue,which detected by the method of Western blotting and immunofluorescent staining(P＜0.05).Conclusion Acute high-altitude hypoxia can induce to blood-brain barrier disruption through the HIF-1α/AQP4 pathway,resulting in high-altitude cerebral edema.

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

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

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.

AIM To investigate the effects of dried extract powder of Qingre Xiaoyanning on a mouse model of rhinovirus (RhV) infection.METHODS Ninety-six BALB/c mice,half males and half females,were randomly divided into the normal group,the model group,the ribavirin group (60 mg/kg) and the low,medium and high dose groups of dried extract powder of Qingre Xiaoyanning (8.72,17.44,34.89 g/kg) for the administration of the corresponding doses of drugs once daily for 7 days.Except for those of the normal group,the mice of the other groups were intranasally instilled with VR-1187 RhV on the fourth day of the administration.On the second day to the day of the last administration,the mice had their left bronchus and left lung procured for pathological examination;their right lung taken for PCR detection of viral load;their levels of inflammatory factors TNF-α,IL-1β,IL-4,VCAM-1 and IFN-γ in alveolar lavage fluid detected by ELISA;their levels of macrophages,NK cells and lymphocytes detected by flow cytometry;and their pulmonary protein expressions of TLR4,MYD88,IKK-β,IκB and p-IκB detected by Western blot.RESULTS Compared with the model group,the group intervened with high dose dried extract powder of Qingre Xiaoyanning displayed decreased viral load (P<0.01);decreased levels of IL-4,VCAM-1 and IL-1β in bronchoalveolar lavage fluid (P<0.05,P<0.01);decreased proportion of pulmonary macrophages (P<0.01);increased proportion of lymphocytes and NK cells (P<0.05);and decreased protein expressions of TLR4,MYD88,IκB,p-IκB and ratio of p-IκB/IκB in lung tissue (P<0.05).Additionally,the medium dose group of dried extract powder of Qingre Xiaoyanning shared decreased pulmonary IKK-β protein expression (P<0.05).CONCLUSION The dried extract powder of Qingre Xiaoyanning can reduce the inflammatory reaction in mice to protect their lung tissue because of its obvious anti-RhV effect in vivo by inhibiting the RhV replication via TLR4/MYD88/NF-κB signaling pathway.