ObjectiveTo investigate the impact of aberrant SKI expression and its mutations on the biological characteristics of cholangiocarcinoma cell lines QBC939 and RBE， and to explore the underlying molecular mechanisms. MethodsThe Gene Expression Profiling Interactive Analysis 2 （GEPIA2） database was utilized to analyze SKI expression and its clinical relevance in cholangiocarcinoma patients. Lentiviral transduction was employed to establish QBC939 and RBE cell lines with stable SKI overexpression， mutation， or knockdown. Cell proliferation was assessed using CCK-8， colony formation， and EdU assays. Apoptosis and cell cycle distribution were analyzed by flow cytometry. Cell migration was evaluated using Transwell and wound healing assays. The effect of SKI over-expression， mutation， or knockdown on key proteins （SMAD2， SMAD3， SMAD4） in the transforming growth factor-β （TGF-β）/Small mothers against decapentaplegic （SMAD） signaling pathway was examined by Western blot. ResultsCompared to SKI overexpression alone， the introduction of SKI mutations significantly promoted S-phase progression， enhanced proliferation and migration， and inhibited apoptosis. Mechanistically， SKI mutations suppressed the phosphorylation of SMAD2 and SMAD3 proteins， thereby inhibiting the transcriptional activity of the TGF-β signaling pathway. Conversely， SKI knockedown produced the opposite effects. ConclusionSKI gene mutation acts as a gain-of-function genetic alteration， exerting an oncogenic role in cholangiocarcinoma cells. The primary mechanism involves the inhibition of the TGF-β/SMAD signaling pathway， which in turn promotes proliferation and cell cycle progression， and suppresses apoptosis in QBC939 and RBE cells， ultimately driving tumor progression.

Objective: To prepare hollow mesoporous silicon nanoparticles ( HMSNs) loaded with allicin—diallyl trisulfide (DATS) , and to study their feasibility as a therapeutic agent for ischemic injury of lower limbs . Methods: HMSNs were synthesized by selective etching , and their microstructure was observed by scanning and transmis- sion electron microscopy. Their physical and chemical properties were analyzed by X-ray diffraction and dynamic light scattering (DLS) . Their biological safety was tested by erythrocyte hemolysis and cytotoxicity experiments . DATS was loaded into HMSNs by adsorption to obtain DATS sustained release nanoparticles (DATS-HMSNs) , and the cumulative release curve of DATS was calculated and produced by ultraviolet spectrophotometry. C57BL/6 mice were randomly divided into four groups (sham operation group , normal saline group , DATS group , and DATS-HM- SNs group) . Lower limb ischemia models were made by femoral artery ligation and resection . The exercise ability and the contents of tumor necrosis factor alpha (TNF-α ) , interleukin-6 (IL-6) , monocyte chemoattractant protein- 1 (MCP-1) , reactive oxygen species (ROS) , platelet-endothelial cell adhesion molecule (CD31) , alpha smooth muscle actin ( α-SMA) , basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) in muscles of mice in each group before and after limb ischemia were tested . Results : Scanning and transmission e- lectron microscope observation showed that the prepared HMSNs were hollow , spherical and uniform in particle size . DLS results showed that the particle size was (226. 5 ± 11 . 8) nm. The results of red blood cell hemolysis test and cytotoxicity test showed that HMSNs had good biocompatibility. The maximum drug loading rate of HMSNs on DATS was 27. 89% , the cumulative release rate of DATS in 7 days was about 80. 12% , and could reach 97. 27% in 21 days . Compared with the control group , after DATS-HMSNs were applied to mice with lower limb ischemia , immunohistochemical staining showed that the levels of CD31 , α-SMA , bFGF and VEGF increased ( P < 0. 05) . Elisa test showed that the levels of TNF-α , IL-6 , MCP-1 and ROS decreased (P < 0. 05) , and the exercise ability of mice recovered satisfactorily after ischemia. Conclusion DATS-HMSNs can release DATS slowly and continu- ously , providing protection against ischemic injury of lower limbs .

Objective To explore the role of Schlafen4(SLFN4)in acute pneumonia induced by hypervirulent Klebsiella pneumoniae(hvKp)via intratracheal aerosolization.Methods Differential expression gene Slfn4 was identified after infection with hvKp based on RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)data before Slfn4-/-mice were obtained via CRISPR/Cas gene editing technology.Slfn4-/-mice and wild mice were challenged via intratracheal aerosolization.Mortality and weight changes were recorded for 14 d,while pathological changes and expression levels of interleukin-6(IL-6),IL-17A,IL-1β,and tumor necrosis factor-α(TNF-α)were detected at 48 h post-infection.Results SLFN4 expression was significantly increased in wild mice after infection with hvKp.Survival was significantly increased,and weight loss was mitigated before gradual recovery in Slfn4-/-mice after infection.The knockout of SLFN4 attenuated alveolar wall thickening,diminished neutrophil infiltration,and suppressed pro-inflammatory cytokine production(IL-6,IL-17A,IL-1β,TNF-α)in the lung at 48 h post-infection.Conclusion The deletion of SLFN4 may suppress the expression of specific pro-inflammatory cytokines and attenuate neutrophil over-recruitment in the lung,thereby alleviating pneumonia in mice after hvKp infection.

Objective : To identify autophagy-related genes involved in pulmonary infection caused by the highly drug-resistant and virulent methicillin-resistant Staphylococcus aureus strain USA300 ( USA300) ，and to explore the underlying molecular mechanisms ， thereby providing potential targets for immunotherapy． Methods: The GSE220943 dataset of a USA300-induced pulmonary infection mouse model was obtained from the GEO database． Differentially expressed genes ( DEGs ) were identified using the DESeq2 package． Autophagy-related genes ( ARGs) were retrieved from the MSigDB and Autophagy databases．Weighted gene co-expression network analysis ( WGCNA) was performed to construct gene co-expression modules．Genes overlapping among DEGs，ARGs，and WGCNA modules were identified as autophagy-related DEGs．Gene Ontology ( GO) enrichment analysis was con- ducted using the clusterProfiler R package，while Kyoto Encyclopedia of Genes and Genomes ( KEGG) pathway en- richment analysis was performed via the Metascape platform．Immune cell infiltration was analyzed using the Immu- CellAI-mouse website．A protein - protein interaction ( PPI) network was constructed using the STRING database， and hub genes were identified through topological analysis in Cytoscape． Receiver operating characteristic curve ( ROC) curves were plotted via the website https: / /www．bioinformatics．com．cn． Finally，key gene expression was validated in mouse lung tissues by real-time quantitative reverse transcription PCR ( RT-qPCR) ． Results: A total of 6 135，4 075，3 680，and 2 342 differentially expressed genes ( DEGs) were identified at 12，24，48，and 96 hours post-infection，respectively．By integrating DEGs，autophagy-related genes ( ARGs) ，and WGCNA mod- ules，19 autophagy-related DEGs were identified． GO and KEGG enrichment analyses indicated that these genes were mainly involved in CD4 + T cell activation and regulation，innate immune responses，and autophagosome mem- brane formation．Immune infiltration analysis revealed that innate immune cells such as neutrophils and dendritic cells predominated during the early phase of infection，while γδ T cells and M2 macrophages became more promi- nent in the later stages．PPI network analysis identified 12 hub autophagy-related genes，among which three upreg- ulated key genes ( Eif2ak2，Ikbke，and Nfkbiz) were further confirmed．The area under the ROC curve for all three genes was 1. 000．RT-qPCR validation demonstrated significantly elevated expression of these three genes in lung tissues at 24 hours post-infection ( all P＜0. 05) ． Conclusion Eif2ak2，Ikbke，and Nfkbiz may be involved in the pulmonary infection caused by USA300 by promoting autophagy and hold promise as potential targets for immuno- therapy．

This paper systematically summarizes the practical experience of the 2025 Dingri earthquake emergency medical rescue in Tibet. It analyzes the requirements for earthquake medical rescue under conditions of high-altitude hypoxia, low temperature, and low air pressure. The paper provides a detailed discussion on the strategic layout of earthquake medical rescue at the national level, local government level, and through social participation. It covers the construction of rescue organizational systems, technical systems, material support systems, and information systems. The importance of building rescue teams is emphasized. In high-altitude and cold conditions, rapid response, scientific decision-making, and multi-party collaboration are identified as key elements to enhance rescue efficiency. By optimizing rescue organizational structures, strengthening the development of new equipment, and promoting telemedicine technologies, the precision and effectiveness of medical rescue can be significantly improved, providing important references for future similar disaster rescues.

OBJECTIVE To analyze the investigation and handling process of a suspected outbreak of hospital-ac-quired Serratia marcescens infection in the Neonatal Intensive Care Unit(NICU)of a certain hospital,and to pro-vide valuable reference for the prevention and control of hospital-acquired infections.METHODS An epidemiologi-cal investigation was conducted on three S.marcescens-positive neonates admitted to the NICU of the Affiliated Hospital of Guizhou Medical University from Oct.12 to 18,2024.Environmental hygiene sampling was carried out on the surfaces of the ward.The homology of the strains was analyzed,and effective intervention measures were taken.RESULTS The incidence of S.marcescens sepsis in the NICU from Oct.12 to 18,2024 was 2.20％(2/91)compared to 2.35％in the same period of 2023(2/85),no significant difference was found between the two time periods(P=0.946).Among the three S.marcescens-positive NICU neonates,one was considered com-munity-acquired,while the other two were diagnosed with S.marcescens sepsis.A total of 59 environmental hy-giene samples were collected,with one sample detecting S.marcescens in the bedside infusion pump slot of case 1.The homology analysis results showed high homology among the four S.marcescens strains but not completely homologous.After effective preventive and control measures were implemented,suspected S.marcescens cluste-ring events didn't further occurred.CONCLUSION The occurrence of this incident may be attributed to inadequate cleaning and disinfection of environmental surfaces and improper hand hygiene practices by some medical staff.

OBJECTIVE To analyze the epidemiological characteristics of fungal infections in patients of intensive care unit(ICU)of a tertiary general hospital from 2020 to 2024 and explore the prognosis of the ICU patients with fungal sepsis and the influencing factors so as to provide guidance for optimization of prevention,control and treat-ment strategies for the fungal infections.METHODS The data with regard to the isolation of 1131 strains of non-repetitive fungi from ICU patients were retrospectively collected from the Affiliated Hospital of Guizhou Medical University between 2020 and 2024.The sources of specimens and mortality rates of patients with different types of fungal infections were observed.The treatment outcomes of the patients with the infections of different sources of specimens were assessed by Kaplan-Meier survival curve and Log-rank test.The risk factors for death were screened out through univariate analysis.RESULTS The respiratory tract specimens were the main source where the strains were isolated,accounting for 56.68％;Candida albicans was the absolute predominance,accounting for 73.47％.The mortality rate of the patients with Candida parapsilosis infection reached up to 29.17％.The mortality rate of the patients with blood infections was the highest(33.82％,P＜0.001),and the patients with the source of blood infections had the poorest prognosis(P=0.019).The echinocandins were the most com-monly used for antifungal therapy,accounting for 52.05％.CONCLUSIONS The ICU is a place where the fun-gal infections are highly prevalent.The high morality rate is associated with the blood source infections and specific species.It is crucial for improvement of prognosis to identify the high-risk patients in early stage and optimize the antifungal strategies.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Objective To explore the effects of S100 calcium-binding protein A9 (S100A9) gene knockout on the phenotype of systemic lupus erythematosus (SLE) in mice and to clarify the role of S100A9 in the pathogenesis of SLE. Methods Ten female C57BL/6 wild-type and S100A9 knockout (S100A9-KO ) mice were selected, with five wild-type and five S100A9-KO B6 mice receiving imiquimod (IMQ) cream to establish SLE mouse model. The other five wild-type and five S100A9-KO B6 mice were treated as control groups by wiping the skin of the right ear with a cotton swab. After 8 weeks, the mice were sacrificed. The serum was collected from each mouse to detect the levels of anti-double-stranded DNA (dsDNA) antibodies, immunoglobulin G (IgG), B cell activating factor (BAFF), and interleukin 6 (IL-6) using ELISA. The levels of serum creatinine were determined using a sarcosine oxidase method. Urine was collected to measure urinary protein concentration. Kidneys were collected and stained with hematoxylin and eosin (H&E) for evaluating histological changes. Results After IMQ treatment, the length and weight of spleen, levels of serum creatinine, anti-dsDNA antibodies, IgG, BAFF, IL-6, and urinary protein in the IMQ B6 group and IMQ S100A9-KO B6 group were significantly higher than those of the control groups. Lupus-like changes including increased glomerular volume and tubular epithelial swelling were observed in kidneys from the IMQ and IMQ S100A9-KO groups. However, compared with the IMQ B6 group, the IMQ S100A9-KO B6 group exhibited milder levels of serum and urine indicators as well as the lupus-like symptoms. Conclusion IMQ could induce lupus-like symptoms in both wild-type B6 mice and S100A9-KO B6 mice, but the lesions in S100A9 knockout mice are milder. Theses results suggested that S100A9 is involved in and promotes the pathogenesis of SLE.
Animals ; Lupus Erythematosus, Systemic/chemically induced* ; Female ; Calgranulin B/genetics* ; Mice, Knockout ; Mice, Inbred C57BL ; Phenotype ; Mice ; Interleukin-6/blood* ; Disease Models, Animal ; Antibodies, Antinuclear/blood* ; B-Cell Activating Factor/blood* ; Immunoglobulin G/blood* ; Kidney/pathology*