Objective: To develop a prediction model for mild cognitive impairment (MCI) risk among the elderly, so as to provide a tool for MCI early screening. Methods : From July 2022 to September 2024, a multi-stage stratified random cluster sampling method was used to recruit permanent residents aged ≥65 years from the Xinjiang Uygur Autonomous Region as study participants. Data on sociodemographic characteristics, nutritional status, body composition indices, bone mineral density, and handgrip strength were collected through questionnaires and physical examinations. Sarcopenia was defined based on appendicular skeletal muscle index and handgrip strength. MCI was assessed using the Mini-Mental State Examination, with adjustments for educational level. Participants were randomly divided into a training set and a validation set in a 7∶3 ratio. LASSO regression and multivariable logistic regression models were employed to screen for predictors and construct an MCI risk prediction model. The predictive performance of the model was evaluated using receiver operating characteristic (ROC) curve and decision curve analysis (DCA). Results: A total of 1 641 participants were surveyed, including 755 males (46.01%) and 886 females (53.99%). The majority of participants were aged 65-<75 years, comprising 1 154 individuals (70.32%). MCI was detected in 517 participants, corresponding to a detection rate of 31.51%. Resultsfrom LASSO regression and multivariate logistic regression analysis showed that residence (rural, OR = 2.323, 95% CI: 1.682-3.210), age (75-<85 years, OR = 1.405, 95% CI: 1.019-1.937; ≥85 years, OR = 3.655, 95% CI: 1.696-7.875), educational level (primary school, OR = 0.341, 95% CI: 0.247-0.472; junior high school, OR = 0.255, 95% CI: 0.160-0.408; high school, OR = 0.286, 95% CI: 0.154-0.531; bachelor's degree or above, OR = 0.120, 95% CI: 0.041-0.351), history of alcohol consumption (yes, OR = 3.216, 95% CI: 2.164-4.779), risk of malnutrition (yes, OR = 1.464, 95% CI: 1.064-2.014), sarcopenia (yes, OR = 3.197, 95% CI: 2.332-4.385), and waist-to-hip ratio (abnormal, OR = 1.540, 95% CI: 1.159-2.048) were identified as predictive factors for MCI among the elderly. In the training set, the area under the ROC curve, sensitivity, and specificity were 0.788, 0.719, and 0.712, respectively. In the validation set, the corresponding values were 0.784, 0.913, and 0.542, respectively. DCA demonstrated that the model provided a higher clinical net benefit for predicting MCI risk when the risk threshold probability ranged from 0.124 to 0.764. Conclusion The prediction model developed in this study demonstrates good discriminative ability and clinical utility, indicating its substantial value for predicting the MCI risk among the elderly.

Background/Aims: Natural killer (NK) cell function is generally considered dampened in chronic hepatitis B virus (HBV) infection; however, the NK cell pool exhibits phenotypic and functional heterogeneity, and the antibody--mediated effect of NK cells remains less characterized. This study evaluated the dynamic changes in antibody-mediated NK cell responses and the involvement of distinct NK subsets across disease stages and during antiviral treatment. Methods: A T-cell receptor-like antibody specific for the HBV core 18–27 peptide (cTCRL-Ab) was used to determine the antibody-mediated effect of NK cells, and an array of NK cell surface markers were analyzed in cross-sectional and longitudinal cohorts of patients with chronic HBV infection. Single-cell RNA sequencing (scRNA-seq) was performed to identify the heterogeneity of NK subsets. Results: The cTCRL-Ab enabled the detection of NK cell cytolytic activity and IFNγ production. Notably, cTCRL-Ab-mediated NK cell responses were compromised in chronically HBV-infected patients, particularly in those receiving pegylated interferon-α (Peg-IFNα), which was associated with the downregulation of CD16 expression. Correspondingly, Peg-IFNα inhibited cTCRL-Ab-mediated NK cell function by reducing CD16 expression in vitro. scRNA-seq revealed that CD16 downregulation occurred mainly within a dysfunctional CD16hi NK subset exhibiting exhaustion properties. In contrast, an activated CD16hiNK subpopulation (CX3CR1⁺KLRC2–CD16hi) with high cytotoxicity was enriched in patients who experienced favorable treatment responses. Furthermore, the intrahepatic CX3CR1+KLRC2–CD16hi subset tended to exhibit functional restoration in HBsAg-loss individuals. Conclusions Our data contribute to the understanding of antibody-mediated responses of NK cells in chronic HBV infection, and highlight a previously unappreciated functional CX3CR1+KLRC2–CD16hiNK subset as a potential therapeutic target.

BACKGROUND:In previous studies,the equivalent structure of three-dimensional cell reconstruction of tissue engineering oral mucosa is similar to normal oral mucosa,including epithelial-like structure,lamina propria-like structure,and vascular lumen-like structure,and has initially achieved the establishment of vascular equivalent,but its vascularization characteristics are not very clear.OBJECTIVE:Vascular-like structures of vascularized oral mucosa equivalent were obtained by targeting vascular endothelial cells specific marker expression profiles correlated with laser capture microdissection system,and their vascularization ability was evaluated to reveal their vascularization characteristics.METHODS:Human gingival epithelial cells were cultured from human gingival epithelium and human gingival fibroblasts,human gingival mesenchymal stem cells were cultured from human gingival lamina propria.Human gingival mesenchymal stem cells were induced to differentiate into vascular endothelial-like cells after monoclonal expansion culture.Human gingival epithelial cells,human gingival fibroblasts,and vascular endothelial-like cells were loaded with acellular vascular matrix-0.25%human-like collagen type Ⅰ scaffold to construct the vascularized oral mucosa equivalent.The layered structure of oral mucosa equivalent(experimental group)and the acellular vascular matrix-0.25%human-like collagen type Ⅰ scaffold(control group)were implanted subcutaneously into the back of nude mice,respectively.14 days later,the incision surface of the two groups was coated with biogel.The biogel surface of the experimental group was inoculated with human gingival epithelial cells,while the control group was not inoculated with cells.The samples were collected after 14 days of feeding.The layered structure of oral mucosa equivalent was observed by morphology.The neovascular-like structures in oral mucosa equivalents were labeled by immunohistochemistry and immunofluorescence with a more comprehensive expression profile of vascular endothelial cells,and the vascularization characteristics were analyzed.A laser capture microdissection system was used to capture the neovascularization structures in the oral mucosa equivalents specifically labeled by immunohistochemistry and analyze their vascularization characteristics.RESULTS AND CONCLUSION:(1)The morphology showed that the cell level of oral mucosa equivalent was clear,and the structure was similar to that of normal oral mucosa,that is,there were epithelioid structures,lamina-like structures,and vascular cavelike structures,and there were scattered erythrocytes in the vascular cavelike structures.(2)The results of EdU Apollo tracer seed cells in the oral mucosa equivalent group showed that human gingival epithelial cells labeled with EdU Apollo 488 showed green fluorescence expression.DAPI labeled human gingival fibroblasts showed blue fluorescence expression and formed lamina-like structures in vivo.EdU Apollo 567 labeled vascular endothelial-like cells showed red fluorescence expression and formed a vascular-like structure in vivo.(3)Vascular endothelial cell specific marker expression profile immunofluorescence labeling of vascular structure showed that compared with normal oral mucosa,the expressions of CD31,CD51,CD54,CD105,Tie-2,VWF,vascular endothelial growth factor receptor 1,and vascular endothelial growth factor receptor 2 in oral mucosa equivalents were increased(P<0.000 1).There were no significant changes in CD34 expression(P>0.05).(4)Compared with the specifically labeled oral mucosal vascular structures,the expression levels of CD51,CD54,CD105,Tie-2,VWF,vascular endothelial growth factor receptor 1,and vascular endothelial growth factor receptor 2 of the oral mucosa equivalents targeted by the laser capture microdissection system were increased(P<0.000 1).There were no significant changes in expression of CD31 and CD34(P>0.05).(5)The results showed that the oral mucosa equivalent reconstructed by three-dimensional cell stratification could achieve good vascularization,and its vascularization characteristics were consistent with the immunological function and characteristics of neovascularization.Vascularization helps three-dimensional cell layer reconstruction of oral mucosa equivalent regeneration.

Objective:To investigate impacts of evodiamine(EVO)on brain injury and immune function in rats with hemor-rhagic traumatic shock(HTS)by regulating CC chemokine ligand 2(CCL2)-CC chemokine ligand receptor 2(CCR2)signaling axis.Methods:Rats were randomly grouped into HTS group,EVO low(EVO-L,10 mg/kg EVO),medium(EVO-M,20 mg/kg EVO),high-dose(EVO-H,40 mg/kg EVO)groups,EVO-H+CCL2 group(40 mg/kg EVO+5 ng CCL2 recombinant protein)and sham sur-gery group.After intervention,kits were applied to detect myeloperoxidase(MPO),superoxide dismutase(SOD),malondialdehyde(MDA),IL-6 and TNF-α levels;HE staining was applied to detect morphological changes in brain tissue;immunohistochemical method was applied to detect β-amyloid precursor protein(β-APP)expression;flow cytometry quantification was applied to detect T lymphocyte subpopulations contents;Western blot was applied to detect CCL2 and CCR2 proteins expressions in brain tissue.Results:Compared with sham surgery group,neuronal damage in HTS group was severe,IL-6,TNF-α,MPO,MDA levels,β-APP positive cell ratio,CCL2,CCR2 expressions and CD8+T cells were obviously increased,SOD,CD4+T/CD8+T,CD4+T and CD3+T cells were obviously reduced(P<0.05);compared with HTS group,brain tissue morphology of rats in EVO-L,EVO-M and EVO-H groups were improved,IL-6,TNF-α,MPO,MDA levels,β-APP positive cell ratio,CCL2,CCR2 expressions and CD8+T cells were obviously re-duced,SOD level,CD4+T/CD8+T,CD4+T and CD3+T cells were obviously increased,which in a dose dependent manner(P<0.05);compared with EVO-H group,IL-6,TNF-α,MPO,MDA levels,β-APP positive cell ratio,CCL2,CCR2 expressions and CD8+T cells in EVO-H+CCL2 group were obviously increased,SOD level,CD4+T/CD8+T,CD4+T and CD3+T cells were obviously reduced(P<0.05).Conclusion:EVO reduces brain injury and improves immune function in HTS rats by inhibiting CCL2-CCR2 signaling pathway.

OBJECTIVE: To investigate the frequency and related factors of ineffective triggering (IT) and double triggering (DT) in patients with acute brain injury undergoing invasive mechanical ventilation. METHODS: A retrospective cohort study was conducted using data from a single-center observational trial. Patients with acute brain injury [traumatic brain injury, stroke, and post-craniotomy for brain tumors] undergoing mechanical ventilation in the intensive care unit (ICU) of Beijing Tiantan Hospital, Capital Medical University between June 2017 and July 2019 were retrospectively analyzed. Demographic and clinical data were collected. Respiratory parameters and waveforms during the first 3 days of mechanical ventilation were recorded, with 15-minute waveform segments collected 4 times daily. Airway occlusion pressure (P_0.1) was measured via end-expiratory hold at the end of each recording. IT and DT were identified based on airway pressure, flow, and esophageal pressure waveforms, and the ineffective triggering index (ITI) and DT incidence were calculated. Multivariate Logistic regression was used to identify factors associated with IT and DT. RESULTS: A total of 94 patients with acute brain injury were ultimately enrolled, including 19 cases of traumatic brain injury (20.2%), 39 cases of stroke (41.5%), and 36 cases of post-craniotomy for brain tumor (38.3%). Supratentorial injury was observed in 49 patients (52.1%), while infratentorial injury was identified in 45 patients (47.9%). A total of 94 patients with 1 018 datasets were analyzed; 684 (67.2%) datasets were on pressure support ventilation (PSV), and 334 (32.8%) were on mandatory ventilation. IT was detected in 810 (79.6%) datasets, with a median incidence of 2.1% (0.3%, 12.0%). Datasets demonstrating IT were characterized by lower P_0.1, higher tidal volume (VT), reduced respiratory rate (RR), and decreased minute ventilation (MV) compared to those without IT. The proportion of datasets exhibiting IT was higher during PSV than in mandatory ventilation [83.8% (573/684) vs. 71.0% (237/334), P < 0.05], while, the prevalence of ITI ≥ 10% was lower [23.8% (163/684) vs. 33.5% (112/334), P < 0.05]. DT was detected in 305 datasets (30%), with a median incidence of 0.6% (0.4%, 1.3%). Datasets exhibiting DT were characterized by higher VT, reduced RR, and lower pressure support levels. The incidence of DT was lower in PSV compared to mandatory ventilation modes [0% (0%, 0.3%) vs. 0% (0%, 0.5%), P < 0.05]. The post-craniotomy for brain tumors group exhibited higher ITI, lower RR, reduced MV, and a greater proportion of infratentorial lesions, compared to the TBI group. The infratentorial lesion group demonstrated higher ITI and incidence of DT compared to the supratentorial lesion group [ITI: 3.1% (0.7%, 17.8%) vs. 1.5% (0%, 8.3%), incidence of DT: 0% (0%, 0.5%) vs. 0% (0%, 0%), both P < 0.05]. After adjusting for confounding factors through multivariate logistic regression analysis, infratentorial lesion [odds ratio (OR) = 2.029, 95% confidence interval (95%CI) was 1.465-2.811, P < 0.001], lower P_0.1 (OR = 0.714, 95%CI was 0.616-0.827, P < 0.001), and mandatory ventilation (OR = 1.613, 95%CI was 1.164-2.236, P = 0.004) were independently associated with IT. Additionally, infratentorial lesion (OR = 1.618, 95%CI was 1.213-2.157, P = 0.001), large tidal volume (OR = 1.222, 95%CI was 1.137-1.314, P < 0.001), lower pressure support levels (OR = 0.876, 95%CI was 0.829-0.925, P < 0.001), and mandatory ventilation (OR = 2.750, 95%CI was 1.983-3.814, P < 0.001) were independently associated with DT. CONCLUSION IT and DT were common in patients with acute brain injury. Infratentorial lesions and mandatory ventilation were independently associated with both IT and DT.
Humans ; Respiration, Artificial/methods* ; Retrospective Studies ; Brain Injuries/therapy* ; Intensive Care Units ; Male ; Female ; Middle Aged ; Brain Injuries, Traumatic/therapy* ; Logistic Models ; Aged ; Adult

Objective To understand the clinical characteristics of patients with Streptococcus anginosus group(SAG)pulmonary abscess and resistance of SAG.Methods 67 patients with pulmonary abscess admitted to a hos-pital from January 2018 to May 2022 were retrospectively analyzed,clinical data of patients with SAG pulmonary abscess were analyzed,and the minimum inhibitory concentration of antimicrobial agents to 18 SAG strains was de-tected by microbroth dilution method,the carriage of resistance genes and virulence genes of SAG were detected by high-throughput sequencing technology.Results Among 67 patients with pulmonary abscess,SAG accounted for 29.9％(20/67),out of which 2 were excluded due to bacterial inactivation,and 18 patients were included for fur-ther studies.18 patients with SAG pulmonary abscess were all community acquired,with an average age of(60.9±9.1)years.There were 13(72.2％)male patients,most patients(94.4％)complicated chronic pulmonary disease,with cough(94.4％)and expectoration(88.9％)as the initial symptoms,some patients(44.4％)had chest pain,and more than half(61.1％)didn't have fever.The proportion of neutrophils,erythrocyte sedimentation rate,and C-reactive protein were mostly elevated,while procalcitonin was normal.The resistance rate of 18 SAG strains to erythromycin,clindamycin,and tetracycline was＞65％,out of which 14 strains carried resistance gene ermB,13 strains carried resistance gene tetM,and 1 strain carried both resistance gene msrD and mefA.18 SAG strains were detected virulence gene psaA,out of which 3 strains were detected virulence gene nan A.Conclusion SAG is an im-portant pathogen that causes pulmonary abscess,and the patients'complications are mainly chronic pulmonary di-seases,with non-specific clinical manifestations;Most strains carry ermB and tetM genes,mediating resistance to macrolides,lincosamides,and tetracyclines.

Objective To explore the mechanism of Shengmai Decoction in improving heart failure by regulating mitochondrial apoptosis based on network pharmacology and experimental verification;To provide a basis for its clinical application.Methods The active components and targets of Shengmai Decoction were obtained through TCMSP and TCMID databases.Heart failure and mitochondrial apoptosis related targets were retrieved from GeneCards,OMIM,DrugBank,PharmGKB and TTD databases.A protein-protein interaction(PPI)network at the intersection of drugs and diseases was constructed using the STRING database,and a component-target network was constructed using Cytoscape 3.8.2 software.GO and KEGG pathway enrichment analysis was performed on intersecting targets using the DAVID database.Molecular docking was conducted to assess the binding affinity of key components to core target proteins.A rat model of heart failure was established,and the cardiac function of rats were detected by echocardiogram,ELISA was used to detect serum contents of BNP and NT-proBNP,mitochondrial ultrastructure was observed by transmission electron microscope,and Western blot was used to detect protein expressions of Bcl-2/Bax/Caspase-3 signaling pathway.Results A total of 66 active components and 146 targets of Shengmai Decoction were identified,and 22 intersecting targets with heart failure and mitochondrial apoptosis,including key proteins such as TNF,Bcl-2,Bax and Caspase-3.GO enrichment analysis revealed that the intersecting targets were closely associated with inflammation and cell signaling,while KEGG pathway analysis showed that the targets were primarily involved in the TNF signaling pathway,IL-17 signaling pathway,and mitochondrial function regulation.Molecular docking results indicated that Ginsenoside rh2,Beta-sitosterol and other components of Shengmai Decoction exhibited strong binding affinities with Bcl-2,Bax and Caspase-3.Animal experiments demonstrated that Shengmai Decoction significantly improved cardiac function(P<0.05,P<0.01),reduced serum BNP and NT-proBNP contents(P<0.01),alleviated mitochondrial damage,and inhibited mitochondrial apoptosis by upregulating Bcl-2 and downregulating Bax and Caspase-3 protein expression(P<0.01),thereby protecting cardiomyocytes.Conclusion Shengmai Decoction can target and regulate the Bcl-2/Bax/Caspase-3 signaling pathway,improving pathological processes associated with heart failure,which can provide a foundation for clinical optimization of Shengmai Decoction.

Objective:To investigate impacts of evodiamine(EVO)on brain injury and immune function in rats with hemor-rhagic traumatic shock(HTS)by regulating CC chemokine ligand 2(CCL2)-CC chemokine ligand receptor 2(CCR2)signaling axis.Methods:Rats were randomly grouped into HTS group,EVO low(EVO-L,10 mg/kg EVO),medium(EVO-M,20 mg/kg EVO),high-dose(EVO-H,40 mg/kg EVO)groups,EVO-H+CCL2 group(40 mg/kg EVO+5 ng CCL2 recombinant protein)and sham sur-gery group.After intervention,kits were applied to detect myeloperoxidase(MPO),superoxide dismutase(SOD),malondialdehyde(MDA),IL-6 and TNF-α levels;HE staining was applied to detect morphological changes in brain tissue;immunohistochemical method was applied to detect β-amyloid precursor protein(β-APP)expression;flow cytometry quantification was applied to detect T lymphocyte subpopulations contents;Western blot was applied to detect CCL2 and CCR2 proteins expressions in brain tissue.Results:Compared with sham surgery group,neuronal damage in HTS group was severe,IL-6,TNF-α,MPO,MDA levels,β-APP positive cell ratio,CCL2,CCR2 expressions and CD8+T cells were obviously increased,SOD,CD4+T/CD8+T,CD4+T and CD3+T cells were obviously reduced(P<0.05);compared with HTS group,brain tissue morphology of rats in EVO-L,EVO-M and EVO-H groups were improved,IL-6,TNF-α,MPO,MDA levels,β-APP positive cell ratio,CCL2,CCR2 expressions and CD8+T cells were obviously re-duced,SOD level,CD4+T/CD8+T,CD4+T and CD3+T cells were obviously increased,which in a dose dependent manner(P<0.05);compared with EVO-H group,IL-6,TNF-α,MPO,MDA levels,β-APP positive cell ratio,CCL2,CCR2 expressions and CD8+T cells in EVO-H+CCL2 group were obviously increased,SOD level,CD4+T/CD8+T,CD4+T and CD3+T cells were obviously reduced(P<0.05).Conclusion:EVO reduces brain injury and improves immune function in HTS rats by inhibiting CCL2-CCR2 signaling pathway.

AIM To investigate effects of petroleum ether fraction from Derris eriocarpa How on glucose and lipid metabolism in a mouse model of metabolic syndrome(MS).METHODS KM mice were fed a high-fat diet and administered streptozotocin intraperitoneally to establish MS models.The MS mice were then randomly assigned to the model group,the metformin hydrochloride group,the lovastatin group,the ursolic acid group,and the high-,medium-and low-dose D.eriocarpa petroleum ether fraction groups,with 10 mice in each group.Ten additional mice maitained on a normal diet served as the normal control group.After 4 weeks of intragastric administration,glucose and lipid metabolism indicators were measured.Hepatic pathological changes were assessed using HE staining and oil red O staining.Liver tissue mRNA expressions of ATF3,PEPCK,FXR,CYP7A1,HNF4ɑ,CYP8B1 and SRB1 were quantified by RT-qPCR.Hepatic protein expressions of ATF3,HNF4ɑ,PEPCK,FXR and CYP7A1 was analyzed by Western blot in MS mice.RESULTS Compared to the model group,the high-dose D.eriocarpa petroleum ether fraction group exhibited significant glucose tolerance improvement(reduced OGTT-AUC,P＜0.01);favorable serum lipid modulation in terms of increased HDL-C levels(P＜0.01)and decreased TG,TC,LDL-C(P＜0.01);reduced renal biomarkers(BUN,SCR)and hepatotoxic indicators of TBA,AST and ALT activities(P＜0.01);alleviated hepatic lipid accumulation and histopathological damage;downregulated mRNA and protein expressions of ATF3,HNF4ɑ and PEPCK,as well as CYP8B1 mRNA expression(P＜0.01);and upregulated mRNA and protein expressions of FXR and CYP7A1,along with SRB1 mRNA expression(P＜0.01).CONCLUSION D.eriocarpa petroleum ether fraction ameliorates glucose and lipid metabolism dysregulation in MS mice by modulating the ATF3/HNF4ɑ/CYP7A1 signaling pathway,consequently eliciting hypoglycemic,hypolipidemic,hepatoprotective and nephroprotective effects.

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.