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 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．

OBJECTIVE To investigate the molecular epidemiological characteristics of clinical Haemophilus influ-enzae(Hin)isolates from adults and children with community-acquired pneumonia(CAP)so as to provide theo-retical bases for effective prevention and treatment of Hin infection.METHODS The patients who were hospital-ized in respiratory and critical care medicine department and pediatrics department of Xinjiang Production and Con-struction Corps Hospital due to CAP from Jan.2023 to Dec.2024 were enrolled in the study,and the positive rates of Hin in sputum specimens were statistically analyzed.The clinical distribution and results of drug suscepti-bility testing for Hin strains were observed and compared between the adults with CAP and the children with CAP.The capsular types,drug resistance genes and multilocus sequencing typing(MLST)subtypes were detected for 72 strains of Hin.RESULTS The positive rate of Hin was higher among the children with CAP(9.46％)than among the adults with CAP(2.71％).The Hin was more prevalent among the children with CAP than among the adults,it was highly prevalent in autumn and winter,with the population dominated by the children aged between 13 and 17 years old(12.67％).The positive rate of β-lactamase-producing Hin strains was 74.71％among the a-dult patients and 90.17％among the children,respectively;the drug resistance rates to ampicillin were highest(73.86％and 92.57％),the drug resistance rates of the strains isolated from the children to the two types of β-lac-tams were higher than those of the strains isolated from the adults(P＜0.05).The non-typeable Hin strains(94.45％)were the predominant type among the 72 strains of Hin,the production of β-lactamase mediated by blaTEM-1 was the major drug resistance mechanism.The result of MLST showed that CC155(ST-155),CC11(ST-103)and CC107(ST-1002)were the main subtypes.CONCLUSIONS The β-lactamase-producing non-typeable Hin strains are dominant among the Hin strains isolated from the adults and children with CAP in this area.The isolation rate of the strains is high among the children than among the adults.The strains are highly prevalent in autumn and winter,and ST-155 is the predominant clone type.The strains are highly resistant to ampicillin,which should be attached great importance to.

Triple-negative breast cancer (TNBC) remains a refractory subtype of breast cancer due to its resistance to various therapeutic strategies. In this study, we introduce a "brake-release and accelerator-pressing" approach to engineer a microneedle patch embedded with copper-doped Prussian blue nanoparticles (Cu-PB) and the ferroptosis inducer sorafenib (SRF) for raised chemodynamic (CDT)/photothermal (PTT) combination therapy against TNBC. Upon transdermal insertion, the dissolving microneedles swiftly disintegrate and facilitate the release of SRF. Under gentle external light exposure, copper ions (Cu²⁺) and iron ions (Fe³⁺) were liberated from Cu-PB. The direct chelation of Cu²⁺ and the indirect suppression by SRF, collectively attenuate glutathione peroxidase 4 (GPX4) enzymatic function, destabilizing the cellular redox equilibrium (referred to as the "brake-release" strategy). The release of Cu²⁺ and Fe³⁺ ions instigates a Fenton/Fenton-like reaction within tumor cells, further yielding hydroxyl radicals and elevating reactive oxygen species (ROS) concentrations (referred to as the "accelerator-pressing" strategy). This overwhelming ROS accumulation, coupled with the impaired clearance of resultant lipid peroxides (LPO), ultimately triggers a robust ferroptosis cell death response. In summary, this study presents an innovative combinatorial therapeutic strategy based on dual-ferroptosis induction for TNBC, implying a promising therapeutic platform for developing ferroptosis-centered treatments for this aggressive breast cancer subtype.

Objective To construct a predictive model for cerebral small vessel disease (CSVD) MRI burden based on β2-microglobulin (β2-MG) and lipoprotein(a) [Lp(a)], analyze its predictive value, and validate the model. Methods A total of 138 CSVD patients admitted to Anhui No.2 Provincial People’s Hospital from February 2023 to August 2024 were enrolled. Patients were divided into a low-burden group (n=63) and a moderate/severe burden group (n=75) according to the CSVD MRI burden scoring criteria. The related clinical data were compared between the two groups. Binary logistic regression analysis was used to identify independent factors for CSVD moderate/severe MRI burden. A nomogram predictive model was constructed based on these factors and its performance was evaluated. Results The proportions of male patients, as well as those with a history of diabetes or hypertension, were significantly higher in the moderate/severe burden group than those in the low burden group. Additionally, the age of patients in the moderate/severe burden group was significantly older, and the levels of β2-MG, Lp(a), and homocysteine (Hcy) were higher than those in the low burden group (P＜0.01). Binary logistic regression analysis revealed that hypertension, diabetes, β2-MG, and Lp(a) were independent factors for CSVD moderate/severe MRI burden (P＜0.05). The nomogram predictive model based on these four factors had a cut-off value of 0.467 0, with an area under curve (AUC) of 0.838 7 (95%CI 0.760 8-0.916 6) in the training set (n＝97) and 0.854 1 (95%CI 0.742 1-0.966 1) in the internal validation set (n＝41) . The calibration curve demonstrated good agreement between predicted and observed values. Decision curve analysis (DCA) indicated that the nomogram model had good clinical utility. Conclusions The nomogram model based on β2-MG and Lp(a) has high predictive performance in assessing the risk of CSVD moderate/severe MRI burden, with good discrimination and calibration.

OBJECTIVE To investigate the molecular epidemiological characteristics of clinical Haemophilus influ-enzae(Hin)isolates from adults and children with community-acquired pneumonia(CAP)so as to provide theo-retical bases for effective prevention and treatment of Hin infection.METHODS The patients who were hospital-ized in respiratory and critical care medicine department and pediatrics department of Xinjiang Production and Con-struction Corps Hospital due to CAP from Jan.2023 to Dec.2024 were enrolled in the study,and the positive rates of Hin in sputum specimens were statistically analyzed.The clinical distribution and results of drug suscepti-bility testing for Hin strains were observed and compared between the adults with CAP and the children with CAP.The capsular types,drug resistance genes and multilocus sequencing typing(MLST)subtypes were detected for 72 strains of Hin.RESULTS The positive rate of Hin was higher among the children with CAP(9.46％)than among the adults with CAP(2.71％).The Hin was more prevalent among the children with CAP than among the adults,it was highly prevalent in autumn and winter,with the population dominated by the children aged between 13 and 17 years old(12.67％).The positive rate of β-lactamase-producing Hin strains was 74.71％among the a-dult patients and 90.17％among the children,respectively;the drug resistance rates to ampicillin were highest(73.86％and 92.57％),the drug resistance rates of the strains isolated from the children to the two types of β-lac-tams were higher than those of the strains isolated from the adults(P＜0.05).The non-typeable Hin strains(94.45％)were the predominant type among the 72 strains of Hin,the production of β-lactamase mediated by blaTEM-1 was the major drug resistance mechanism.The result of MLST showed that CC155(ST-155),CC11(ST-103)and CC107(ST-1002)were the main subtypes.CONCLUSIONS The β-lactamase-producing non-typeable Hin strains are dominant among the Hin strains isolated from the adults and children with CAP in this area.The isolation rate of the strains is high among the children than among the adults.The strains are highly prevalent in autumn and winter,and ST-155 is the predominant clone type.The strains are highly resistant to ampicillin,which should be attached great importance to.

Objective: To analyze the associations among body mass index (BMI), learning screen/gaming screen exposure and executive function in preschool children in Anhui Province, so as to provide a basis for promoting the development of executive function in preschool children. Methods: In June 2022, a stratified cluster sampling and convenience sampling methods were used to survey 3 534 mothers of preschool children in Wuhu City, Luan City, and Fuyang City, Anhui Province. The Behavior Rating Inventory of Executive Function-Preschool Version (BRIEF-P) was used to assess the preschool childrens executive function abnormalities. Binary Logistic regression was conducted to examine the relationships among BMI, learning screen/gaming screen exposure, and their combined effects on executive function abnormalities. Results: The detection rate of abnormal executive function in preschool children was 9.65%. Logistic regression analysis showed that after adjusting for the confounding factors such as pregnancyinduced hypertension, primary caregivers, family per capita monthly income and family structure, the risk of abnormal executive function of children in overweight/obesity group and high learning screen/gaming screen exposure group increased significantly (overweight/obesity:OR=1.78, 95%CI=1.31-2.42, learning screen exposure:OR=1.48, 95%CI=1.18-1.86, gaming screen exposure:OR=1.50, 95%CI=1.18-1.91,P<0.05). Compared with children with normal BMI and low learning screen/gaming screen screen exposure, those with both overweight/obesity and high learning screen/gaming screen exposure had a significantly greater risk of executive function abnormalities (OR=2.07, 95%CI=1.29-3.31; OR=2.42, 95%CI=1.59-3.68,P<0.05). Conclusions Overweight/obesity and high learning screen/gaming screen exposure are important risk factors for executive function abnormalities in preschool children. Therefore, actively guiding preschool children to develop healthy life habits to promote the normal development of their executive functions is essential.

Seeds are the source for the production of Chinese medicinal materials. The seed authenticity and quality of directly affect the effectiveness and safety of Chinese medicinal materials. The seed quality is faced with the problems such as mixed sources， existence of adulterants and seeds stocked for years， low maturity， and low purity. To ensure the high-quality and sustainable development of the Chinese medicinal material industry， it is urgent to standardize the seed market and identify and evaluate the quality of the seeds circulating in the market. Seed identification methods include visual inspection， microscopic observation， micro-character identification， chemical fingerprinting， molecular identification， electronic nose， X-ray diffraction， electrochemical fingerprinting， spectral imaging， and artificial intelligence. These methods have different application scopes and unique advantages and disadvantages. According to the different species of Chinese herbal medicines and different requirements of testing sites， suitable methods can be selected to achieve rapid and accurate identification with low costs. In the future， the seed identification methods should be developed based on emerging technologies with interdisciplinary knowledge， and intelligent， nondestructive， and single-grain detection methods are needed for the modern Chinese medicinal material industry. This paper introduces the seed identification technologies currently applied in research and production， compares the principles， applicability， advantages， and disadvantages of different technologies， and provides an outlook on the future development of seed identification technologies， aiming to provide a reference for the identification and quality evaluation of seeds of Chinese medicinal material.

Objective To analyze the clinical characteristics and pathogen infection of severe patients with COVID-19 retrospectively.Methods The clinical data and laboratory test results of 85 severe COVID-19 patients combined with pathogenic bacterial infection ad-mitted to the Hospital of Xinjiang Production and Construction Corps from December 1,2022 to February 20,2023 were collected.The patients were divided into the cure group and death group based on the outcome.Meanwhile,the distribution and drug resistance of the infected pathogens were analyzed.Results The median age and length of hospitalization of 85 patients with severe COVID-19 were 82(75,84)years old and 14(9,23)days,respectively.Their most common underlying diseases were hypertension,heart disease,and diabetes.There were 63 patients in the cure group and 22 in the death group,with a mortality rate as high as 25.9%.The levels of white blood cell count,neutrophil to lymphocyte ratio,and C-reactive protein in the patients of the death group were significanly higher than those in the cure group(P<0.05).However,the percentage of lymphocytes was the opposite(P<0.05).A total of 128 strains of pathogenic bacteria were isolated from 85 patients.Among them,21 strains(16.4%)were Gram-positive bacteria,predominantly Staphylococcus aureus.66 strains(51.6%)were Gram-negative bacteria,mainly Klebsiella pneumoniae,Acinetobacter baumannii,and Pseudomonas aeruginosa.41 strains(32.0%)were fungi,primarily Candida albicans.The proportion of methicillin-resistant Staphylo-coccus aureus(MRSA)was as high as 56%,while those of carbapenem-resistant Klebsiella pneumoniae,Acinetobacter baumannii,and Pseudomonas aeruginosa were 14%,50%,and 18%,respectively.Conclusion The severe COVID-19 patients who are elderly or have underlying diseases may be infected with carbapenem-resistant Klebsiella pneumoniae,Acinetobacter baumannii,Pseudomonas aeruginosa,and MRSA.In clinical practice,rational selection of antibiotics should be made and effective measures should be taken to prevent the spread of multidrug-resistant bacteria and reduce the risk of mortality.