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.

ObjectiveTo compare the morphological characteristics， phenological stages， and chemical components of two traditional Chaenomeles speciosa cultivars—"Luohanqi" and "Pingguohong"， thus providing a basis for new cultivar breeding， standardized cultivation， and quality evaluation of authentic medicinal materials. MethodsThe morphological indices of leaves， floral organs， and fruits of the two cultivars were measured， and the phenological sequences were recorded. Microplate assays and high-performance liquid chromatography （HPLC） were employed to determine the levels of total flavonoids， total phenols， polysaccharides， amino acids， oleanolic acid， and ursolic acid. Finally， comprehensive comparative analysis was conducted. ResultsThe two cultivars exhibited generally similar tree vigor but showed significant differences in internode length， leaf morphology， floral organs， fruit development， and phenological stages. "Luohanqi" had significantly larger leaves ［length： （124.7±11.97） mm vs. （105.06±9.16） mm； width： （47.81±4.68） mm vs. （41.98±5.15） mm］， a wider ovary diameter ［（10.76±1.25） mm vs. （8.28±1.18） mm］， a higher fruit shape index （1.6 vs. 1.2）， and a much higher calyx persistence rate （78.28% vs. 8.02%） than "Pingguohong". Its phenological stages were 7-18 days later than those of "Pingguohong". No significant differences were found in the levels of total flavonoids， total phenols， total polysaccharides， total amino acids， or oleanolic acid， while "Pingguohong" had significantly higher ursolic acid content than "Luohanqi". ConclusionThe two main cultivars of C. speciosa in Xuancheng city， Anhui province exhibit marked differences in leaf morphology， floral organ structure， fruit traits， calyx persistence， phenological stages， and chemical composition. These findings provide a scientific basis for subsequent breeding of new cultivars， targeted cultivation， and studies on quality formation of authentic medicinal materials.

ObjectiveTo compare the morphological characteristics， phenological stages， and chemical components of two traditional Chaenomeles speciosa cultivars—"Luohanqi" and "Pingguohong"， thus providing a basis for new cultivar breeding， standardized cultivation， and quality evaluation of authentic medicinal materials. MethodsThe morphological indices of leaves， floral organs， and fruits of the two cultivars were measured， and the phenological sequences were recorded. Microplate assays and high-performance liquid chromatography （HPLC） were employed to determine the levels of total flavonoids， total phenols， polysaccharides， amino acids， oleanolic acid， and ursolic acid. Finally， comprehensive comparative analysis was conducted. ResultsThe two cultivars exhibited generally similar tree vigor but showed significant differences in internode length， leaf morphology， floral organs， fruit development， and phenological stages. "Luohanqi" had significantly larger leaves ［length： （124.7±11.97） mm vs. （105.06±9.16） mm； width： （47.81±4.68） mm vs. （41.98±5.15） mm］， a wider ovary diameter ［（10.76±1.25） mm vs. （8.28±1.18） mm］， a higher fruit shape index （1.6 vs. 1.2）， and a much higher calyx persistence rate （78.28% vs. 8.02%） than "Pingguohong". Its phenological stages were 7-18 days later than those of "Pingguohong". No significant differences were found in the levels of total flavonoids， total phenols， total polysaccharides， total amino acids， or oleanolic acid， while "Pingguohong" had significantly higher ursolic acid content than "Luohanqi". ConclusionThe two main cultivars of C. speciosa in Xuancheng city， Anhui province exhibit marked differences in leaf morphology， floral organ structure， fruit traits， calyx persistence， phenological stages， and chemical composition. These findings provide a scientific basis for subsequent breeding of new cultivars， targeted cultivation， and studies on quality formation of authentic medicinal materials.

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.

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 .

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 explore the clinical effects of two kinds of nasal bone reductors used for shortened and displaced overlapping external nasal fracture reduction under nasal endoscopy and the impact on ventilation function. Methods:From January 2020 to February 2022, 82 patients with shortened and displaced overlapping external nasal fractures diagnosed and treated in the Department of Otolaryngology, the Second People's Hospital of Hefei were collected as the study subjects. The patients were divided into control group（41 cases） and observation group（41 cases） by random number table method. Both groups underwent closed reduction under nasal endoscopy. The control group was treated with traditional straight nasal bone reductor, and the observation group was treated with gun-shaped hook type nasal bone reductor. The success rate of reduction, follow-up rate, clinical effect, and complications were compared between the two groups. The visual analogue scale（VAS） was used to evaluate the aesthetic effect and functional recovery. Rhinomanometry and acoustic rhinometry were used to evaluate nasal ventilation function. Results:The success rate of one-time reduction in the observation group was significantly higher than that in the control group, and the nasal reduction adaptation time was shorter than that in the control group（P<0.05）. There was no significant difference in the follow-up rate of 95.12% and 92.68% between the two groups. The success rate of one-time reduction in observation group was significantly higher than that in the control group, and the adaptation time for nasal reduction in observation group was shorter than that in the control group（P<0.05）. There was no significant difference in the follow-up rate of 95.12% and 92.68% between the two groups in six months after surgery. the total clinical effective rate in observation group was higher than that in the control group（94.87% vs 76.32%, P<0.05）. After surgery, the scores of nasal aesthetics, nasal congestion and olfactory function in both groups were significantly lower compared with the preoperative scores. All the scores in the observed group were lower than that in the control group（P<0.05）. After surgery, there were significant increases in the minimum cross-sectional area of nasal cavity, volume of nasal cavity and total nasal expiratory volume in both groups. Above indicators in observation group were significantly greater than that in control group. The nasal exhalation and inhalation resistance was significantly lower than that before operation, and the resistance in observation group was significantly lower than that in control group（P<0.05）. The total incidence of complications was lower than that in observation group（P<0.05）. Conclusion:The application of gun-shaped hook-type nasal bone reductor in patients with shortened and displaced overlapping external nasal fractures has better success rate of one-time reduction, adaptation time of nasal reduction and treatment outcome. Moreover, it has more advantages in aesthetic effect of nasal appearance, nasal ventilation function and reduction of complications.
Humans ; Nasal Bone/injuries* ; Male ; Female ; Endoscopy/methods* ; Adult ; Treatment Outcome ; Nose/surgery* ; Middle Aged