OBJECTIVE To focus on the classic NOD-like receptor protein 3 （NLRP3）/Caspase-1/gasdermin D （GSDMD） pyroptosis pathway and explore the mechanism by which Huatan qushi huoxue formula （HQHF） inhibits macrophage pyroptosis to ameliorate metabolic dysfunction-associated steatohepatitis （MASH）. METHODS RAW264.7 cells were divided into 5 groups： Control group （10% blank serum）， Model group [10% blank serum+5 μg/mL lipopolysaccharide （LPS）]， HQHF-L group （2.5% drug-containing serum+7.5% blank serum+5 μg/mL LPS）， HQHF-M group （5% drug-containing serum+5% blank serum+5 μg/mL LPS）， and HQHF-H group （10% drug-containing serum+5 μg/mL LPS）. After 24 h of routine culture post-administration， cells and supernatants were collected for assays. Cell morphology was observed via scanning electron microscopy and phase-contrast microscopy； localization and expression of gasdermin D-N （GSDMD-N） were observed by immunofluorescence. Interleukin-1β （IL-1β） and IL-18 contents in supernatants were detected by ELISA； mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD were measured using real-time PCR and Western blot. RESULTS Compared with the Control group， the Model group showed typical pyroptotic morphology （cell membrane bulging and pore formation）， increased aggregation and fluorescence intensity of GSDMD-N on the cell membrane （ P ＜0.05）， significantly increased the contents of IL-1β and IL-18 in cell supernatants （ P ＜0.05）， and significantly up-regulated mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD in cells （ P ＜0.05）. Compared with the Model group， the HQHF-L， HQHF-M and HQHF-H groups showed improved pyroptotic morphology， reduced membrane localization and significantly weakened fluorescence intensity of GSDMD-N （ P ＜0.05）， significantly decreased the contents of IL-1β and IL-18 in cell supernatants （ P ＜0.05）， and significantly down-regulated mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD in cells （ P ＜0.05）. CONCLUSIONS HQHF inhibits LPS-induced macrophage pyroptosis， and its mechanism of improving MASH may be associated with the suppression of the activation of the classical NLRP3/Caspase-1/GSDMD pyroptosis pathway.

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.

Chronic liver diseases are a group of diseases in which the liver is subjected to a variety of injuries over a long period of time， resulting in irreversible pathological changes that last longer than 6 months. Emodin （EMO） is a natural anthraquinone derivative derived from Rheum officinale， and its pharmacological effect has been extensively studied， exhibiting a variety of biological properties and involving multiple signaling molecules and pathways. Western medicine or surgical treatment is currently the main treatment regimen for chronic liver diseases， and the advance in treatment is limited by various reasons such as side effects and high costs. Due to its natural origin and efficacy， EMO has unique advantages in the treatment of chronic liver diseases and has now become a research hotspot. This article summarizes the therapeutic effect of EMO on chronic liver diseases and its mechanism， in order to provide a certain scientific basis for the traditional Chinese medicine treatment of chronic liver diseases and the development of drugs in clinical practice.

ObjectiveTo analyze the distribution characteristics of traditional Chinese medicine （TCM） syndrome elements in different risk populations of heart failure complicated with type 2 diabetes. MethodsClinical data of 675 type 2 diabetes patients were retrospectively collected. Lasso-multivariate Logistic regression was used to construct a clinical prediction nomogram model. Based on this， 441 non-heart failure patients were divided into a low-risk group （325 cases） and a high-risk group （116 cases） according to the median risk score of heart failure complicated with type 2 diabetes. TCM diagnostic information （four diagnostic methods） was collected for both groups， and factor analysis was applied to summarize the distribution of TCM syndrome elements in different risk populations. ResultsLasso-multivariate Logistic regression analysis identified age， disease duration， coronary heart disease， old myocardial infarction， arrhythmia， absolute neutrophil count， activated partial thromboplastin time， and α-hydroxybutyrate dehydrogenase as independent risk factors for heart failure complicated with type 2 diabetes. These were used as final predictive factors to construct the nomogram model. Model validation results showed that the area under the curve （AUC） of the receiver operating characteristic （ROC） curve for the modeling group and validation group were 0.934 and 0.935， respectively. The Hosmer-Lemeshow test （modeling group P = 0.996， validation group P = 0.121） indicated good model discrimination. Decision curve analysis showed that the curves for All and None crossed in the upper right corner， indicating high clinical utility. The low-risk and high-risk groups each obtained 14 common factors. Preliminary analysis revealed that the main disease elements in the low-risk group were qi deficiency （175 cases， 53.85%）， dampness （118 cases， 36.31%）， and heat （118 cases， 36.31%）， with the primary locations in the spleen （125 cases， 38.46%） and lungs （99 cases， 30.46%）. In the high-risk group， the main disease elements were yang deficiency （73 cases， 62.93%）， blood stasis （68 cases， 58.62%）， and heat （49 cases， 42.24%）， with the primary locations in the kidney （84 cases， 72.41%） and heart （70 cases， 60.34%）. ConclusionThe overall disease characteristics in different risk populations of type 2 diabetes patients with heart failure are a combination of deficiency and excess， with deficiency being predominant. Deficiency and heat are present throughout. The low-risk population mainly shows qi deficiency with dampness and heat， related to the spleen and lungs. The high-risk population shows yang deficiency with blood stasis and heat， related to the kidneys and heart.

Reactive astrocytes, which exhibit a correlation with the degeneration of dopaminergic neurons, are present in a considerable number during the progression of Parkinson's disease (PD). However, the underlying factors shaping astrocyte reactivity and neuroinflammation in PD remain inadequately elucidated. Here, we demonstrate that fibroblast growth factor 7 (FGF7)/FGF receptor 2 (FGFR2) autocrine signaling intensifies astrocyte reactivity and inflammation. Genetic deletion of Arrb2, β-Arrestin2 encoding gene, led to escalated astrocyte reactivity in MPTP-treated mice, which was further substantiated in astrocyte-specific Arrb2 knockdown mice. RNA sequencing profiling of Arrb2 knockout astrocytes identified Fgf7 as a critical effector of astrocyte reactivity. Subsequently, conditional knockdown of Fgf7 and its receptor Fgfr2 in astrocytes elicited advantageous effects for MPTP-treated mice by restraining the inflammatory phenotypic transition of reactive astrocytes. Furthermore, deletion of astrocytic Fgf7 mitigated MPTP-induced pathology in Arrb2 knockout mice. Mechanistically, STAT1 was distinguished as the transcription factor suppressing Fgf7 expression, while β-Arrestin2 counteracted the proteasomal degradation of STAT1 by binding to RNF220, an E3 ubiquitin ligase for STAT1. More importantly, selectively engaging dopamine D2 receptor (Drd2)/β-Arrestin2-biased signaling using the agonist UNC9995 exhibited therapeutic potential in MPTP-treated mice via moderation of astrocytic FGF7 production, thereby restoring balance in astrocyte reactivity. Collectively, our study bridges a crucial knowledge gap by elucidating the novel functions of FGF family members within the central nervous system, particularly within the context of PD. The autocrine signaling of FGF7/FGFR2 represents a novel mechanism and a potential druggable target for modulating astrocyte-derived inflammation.

Background and purpose:SEC14L1P1,a pseudogene of the SEC14 family,is closely associated with the development of various tumors,but its role in oral squamous cell carcinoma(OSCC)has not been clarified.This study aimed to gain insights into the expression characteristics and subcellular localization of SEC14L1P1 in OSCC cells,as well as its effects on OSCC cell proliferation and migration.Methods:The expression of SEC14L1P1 in head and neck squamous cell carcinoma(HNSCC)tissues was analyzed by the ENCORI database;The expression of SEC14L1P1 and its relationship with patient prognosis in HNSCC was further analyzed using the GDC and UCSC Xena databases.The expression of SEC14L1P1 in OSCC cell lines was detected by real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR);RNA nucleoplasmic separation assay was performed to determine the localization of SEC14L1P1 in OSCC cells.SEC14L1P1 knockdown(SS-SEC14L1P1)group and knockdown control(SS-NC)group were established for CAL-27 cells,and SEC14L1P1 overexpression(SEC14L1P1)group and overexpression control(Vector)group were established for HN30 cells.The effects of SEC14L1P1 expression on the proliferation and migration abilities of cells in each group were assessed by cell counting kit-8(CCK-8)and transwell migration assays.RTFQ-PCR and Western blot experiments were used to detect the effects of altered SEC14L1P1 expression on the expression levels of epithelial-mesenchymal transition(EMT)-related genes.To investigate the effects of SEC14L1P1 on the proliferation of OSCC cells in vivo using a subcutaneous xenograft tumor model in nude mice,12 four-week-old BALB/c nude mice were randomly divided into two groups:the antisense oligonucleotide(ASO)-NC group and the ASO-SEC14L1P1 group,with 6 mice in each group.All mice were individually labeled.Further mechanistic studies were performed by analyzing molecules interacting with SEC14L1P1 through the RNAInter database,and the ENCORI database was queried for expression correlation between SEC14L1P1 and DHX9.The effect of altered SEC14L1P1 expression on the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)pathway was detected by Western blot assay.Results:Database analysis showed that the expression of SEC14L1P1 was higher in HNSCC tissues than in normal tissues,and was strongly associated with poor patient prognosis.The RTFQ-PCR results showed that SEC14L1P1 was highly expressed in all six OSCC cell lines;RNA nucleoplasmic separation showed that SEC14L1P1 was mainly localized in the nucleus in CAL-27 and HN30 cells.Compared with SS-NC,the relative expression of SEC14L1P1 in the SS-SEC14L1P1 group was significantly lower and significantly inhibited cell proliferation and migration,while the relative expression of SEC14L1P1 in the SEC14L1P1 group was significantly higher compared with the Vector group,which also significantly increased cell proliferation and migration.The down-regulation of SEC14L1P1 was accompanied by increased mRNA and protein levels of E-cadherin,and decreased mRNA and protein levels of N-cadherin and vimentin,with the opposite result after SEC14L1P1 overexpression.In vivo experiments showed that the xenograft tumor weight and volume of the ASO-SEC14L1P1 group were significantly reduced.Further mechanistic studies revealed a positive correlation between SEC14L1P1 and DHX9 expressions,and DHX9 has been shown to activate the PI3K/AKT signaling pathway.Knockdown of SEC14L1P1 resulted in decreased protein expressions of phosphorylated-PI3K(p-PI3K)and phosphorylated-AKT(p-AKT),and overexpression of SEC14L1P1 increased protein expressions of p-PI3K and p-AKT.Conclusion:SEC14L1P1 showed high expression levels in OSCC cells and tissues and promoted the proliferation and migration of OSCC cells,a phenomenon that may be related to the regulation of the PI3K/AKT signaling pathway by SEC14L1P1,which in turn promotes EMT.

High-quality development of public hospitals requires cultural construction as an endogenous driving force,ai-ming to build a cultural system that integrates systematic,innovative,and humanistic characteristics.Leveraging its century-old historical legacy,Qilu Hospital of Shandong University has established a cultural construction pathway characterized by"strategic planning,heritage preservation,brand building,exemplary leadership,and communication innovation"through five major sys-tems:improving top-level design,inheriting historical heritage,building distinctive brands,cultivating exemplary models,and expanding communication channels.This approach provides cultural and spiritual impetus for the hospital's high-quality develop-ment.Empirical evidence demonstrates that cultural construction in public hospitals must emphasize systematic top-level design,distinctive cultural identity,synergy between tradition and innovation,and long-term sustainability,ultimately transforming cul-tural"soft power"into"hard support"for development.This practice offers a replicable"Qilu Model"for nationwide public hos-pital cultural development,while injecting new connotations into the implementation of the Healthy China strategy.

Objective To investigate the potential mechanisms of action of Huatan Qushi Huoxue Recipe in treating non-alcoholic steatohepatitis(NASH)through network pharmacology and animal experiments.Methods The differentially expressed genes in NASH were obtained from the GEO database.The active components and potential targets of Huatan Qushi Huoxue Recipe were obtained from the TCMSP.The treatment targets were obtained by intersecting the diseases and drug targets.The protein-protein interaction network was analyzed,the drug-active component-target network was constructed,and the enrichment analysis was performed.The key pathways were verified by animal experiments.Results A total of 74differentially expressed genes,97 active components,and 295 potential targets were identified in NASH.Five genes,including JUN,were selected as key targets through intersection.Seven active components,inclu-ding kaempferol and quercetin,were identified.Enrichment analysis revealed that the AGE-RAGE and IL-17 pathways may play a key role in the treatment of NASH by Huatan Qushi Huoxue Recipe.Animal experiments showed that Huatan Qushi Huoxue Recipe could reduce the levels of total cholesterol(TC),triglyceride(TG),and blood glucose(GLU),and down-regulate the expression of RAGE and activator protein 1(AP-1)in the AGE-RAGE and IL-17 pathways,thus,exerting a therapeutic effect on NASH.Conclusion Huatan Qushi Huoxue Recipe can treat NASH by lowering TC,TG and GLU levels and inhibiting the expression of RAGE and AP-1 pro-tein.

Objective To investigate the predictive value of edema metabolic and hematoma dynamics changes on motor and cog-nitive recovery outcomes in patients with intracerebral hemorrhage(ICH).Methods The CT data of ICH patients were collected to evaluate hematoma volume changes from admission to day 3.On day 3,multivoxel magnetic resonance spectroscopy(MRS)was per-formed with region of interest located in the edema region and contralateral normal tissue.Motor and cognitive function recovery was assessed using the simplified F-M scale and the Montreal cognitive assessment(MoCA)on day 3 and at the 3-month follow-up,respec-tively.Overall clinical outcomes were assessed using the Glasgow outcome scale(GOS),and all patients were divided into good and poor outcome groups.Clinical data and metabolic differences in the edema region between the two groups were compared,respec-tively.Logistic regression analysis and receiver operating characteristic(ROC)curves were used to identify and evaluate independent prognostic factors.Subgroup analysis were performed via stratification of hematoma location.Results The logistic regression analy-sis indicated that intraventricular extension,hematoma changes,and the ratio of N-acetyl aspartate(NAA)around the hematoma to contralateral normal brain parenchyma NAA(rNAA)were inde-pendent prognostic factors for poor outcomes(P＜0.05).The area under the curve(AUC)for each factor and the combined model were 0.69,0.73,0.79,and 0.82,respectively.In patients with ICH in the basal ganglia region,△F-M was negatively correlated with hematoma changes and positively correlated with rNAA value(P＜0.001).In patients with ICH in the thalamic and lobar regions,△MoCA was not significantly correlated with hematoma changes(P＞0.05),but was positively correlated with rNAA value(P＜0.001).Conclusion The rNAA holds predictive value for motor and cognitive recovery outcomes following standard treatment.

Objective To explore the potential contributors and obstacles of evidence translation for airway hu-midification management in hospitalized patients with laryngectomy tracheostomy and non-mechanical ventilation,so as to provide references for clinical evidence-based practice.Methods An interview outline and questionnaire were developed according to the consolidated framework for implementation research(CFIR).Using purposive sampling,12 healthcare professionals from Department of Otorhinolaryngology,Head and Neck Surgery of a tertiary hospital in Shanxi Province were recruited for semi-structured interviews,and thematic analysis was applied to extract main themes.The interview themes were transformed into survey items,and a survey was conducted among 42 healthcare professionals in the same department.Results Totally 16 contributors and 20 obstacles were identified across 4 domains:the credibility of the evidence and research team,the external support environment for evidence-based practice,the internal conditions for evidence-based practice,and the role recognition of implementers.Contributors include efficient internal collaboration and communication,and rigorous processes for evidence acquisition.Obstacles include insufficient educational resources,low patient knowledge acceptance capacity,lack of professional value a-mong healthcare staff.Conclusion Evidence translation of the humidification management for patients with non-mechanical ventilation after laryngectomy and tracheostomy was influenced by various factors.Future efforts should focus on constructing targeted airway humidification education content and an evaluation index system,and enhanc-ing the professional value and practical leadership of nursing staff.