ObjectiveTo establish a mouse model of rheumatoid arthritis with interstitial lung disease （RA-ILD） in DBA/1 mice using Porphyromonas gingivalis （Pg） infection combined with collagen-induced arthritis （CIA）， and to comprehensively evaluate pathological characteristics in joints， lungs， and serum. MethodsForty DBA/1 mice were randomly divided into four groups， i.e.， Control， Pg infection （Pg）， CIA， and Pg infection combined with CIA （Pg+CIA）， with 10 mice in each group. Arthritis clinical symptoms were evaluated by recording arthritis incidence and clinical scores. Micro-CT scanning was used to assess knee joint pathology. Histopathological changes and collagen deposition in knee joints and lung tissues were analyzed using hematoxylin-eosin （HE） and Masson staining. Immunohistochemistry was performed to detect protein expression of α-smooth muscle actin （α-SMA）， typeⅠ collagen （ColⅠ）， and fibronectin （FN） in lung tissues. Real-time quantitative polymerase chain reaction（Real-time PCR）was used to measure mRNA expression levels of α-SMA， ColⅠ， FN， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and IL-1β in lung tissues. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of Pg， cyclic citrullinated peptide （CCP）， and immunoglobulin G （IgG）. ResultsJoint lesions： The CIA and Pg+CIA groups showed 100% arthritis incidence， with evident joint redness， swelling， and deformity. The number of affected limbs was 27 and 28， and clinical scores were 68 and 70， respectively. No obvious clinical symptoms were observed in the Pg group. Histopathological and imaging analyses showed severe joint lesions in the CIA and Pg+CIA groups， with significantly increased histopathological scores， bone mineral density， bone volume fraction， trabecular thickness， and trabecular number compared to the Control group （P<0.01）. No obvious joint pathology was observed in the Pg group. Lung lesions： The Pg+CIA group exhibited marked alveolar inflammation， interstitial inflammatory cell infiltration， and alveolar wall thickening， with pronounced blue staining of collagen fibers. Histopathological scores and collagen area ratios were significantly higher than those of the Control， Pg， and CIA groups （P<0.05）. Lung protein and mRNA expression levels of α-SMA， ColⅠ， and FN were markedly increased， and mRNA levels of IL-6， TNF-α， and IL-1β were significantly elevated compared to the Control group （P<0.05）. Serology： The Pg+CIA group showed significantly higher levels of CCP， Pg， and IgG compared with the Control， Pg， and CIA groups （P<0.05）. ConclusionDBA/1 mice subjected to Pg infection combined with CIA exhibited pronounced symptoms and pathological features of RA-ILD， along with elevated serum anti-CCP antibody levels. This model represents a novel RA-ILD mouse model， providing a valuable experimental tool for investigating RA-ILD pathogenesis and developing new therapeutics， and serves as a basis for establishing anti-cyclic citrullinated peptide antibody （ACPA）-positive RA-ILD animal models.

ObjectiveThis paper aims to observe the protective effect of Huamoyan granules on knee osteoarthritis （KOA） and explore whether its protective effect is oriented toward an anti-inflammatory direction by regulation of macrophage polarization， which can effectively inhibit the progression of pathological inflammatory response， reduce the release of inflammatory pain mediators， and downregulate the protein expression level of transient receptor potential vanilloid 1 （TRPV1）， so as to provide experimental evidence for its clinical application and investigate its action mechanism. MethodsAfter adaptive feeding， Sprague-Dawley （SD） rats were randomly divided into six groups： sham group， model group， celecoxib group， and high， medium， and low-dose synovitis granule groups （9.6， 4.8， 2.4 g·kg^-1）. The administration dose of celecoxib capsules was 20 mg·kg^-1. There were 10 rats in the sham group and 12 rats in the model group and each administration group. A KOA animal model was established by means of intra-articular injection of sodium iodoacetate into the knee joint. From the 10^th day of the experiment， each administration group was given intragastric administration at a dose of 10 mL·kg^-1 for 4 weeks. General conditions of rats in each group were assessed daily. The pressure pain threshold （PPT） to mechanical stimulation and joint diameter were recorded. X-ray examination was performed on the right knee joints of rats for imaging analysis. Enzyme linked immunosorbent assay （ELISA） was performed to detect the tumor necrosis factor-α （TNF-α）， serum interleukin-1β （IL-1β）， and other pro-inflammatory cytokines in rat serum samples， as well as the expression levels of neurogenic inflammatory mediators such as nerve growth factor （NGF） and calcitonin gene-related peptide （CGRP）. Histopathological changes in the knee joint synovial tissues were examined by hematoxylineosin （HE） staining. Safranin O-fast green staining was performed to observe and evaluate the degree of knee cartilage lesions. Western blot was employed to quantitatively analyze TRPV1， p38 mitogen-activated protein kinase （p38 MAPK）， and phosphorylated （p）-p38 MAPK in rat knee synovial tissues. Immunofluorescence （IF） was used to measure and assess M1/M2 macrophage polarization. ResultsCompared with those in the sham group， the circumference and joint diameter of the right knee were markedly enlarged in the model group （P<0.01）， while PPTs of rats showed a significant reduction （P<0.01）. The contents of IL-1β， TNF-α， CGRP， and NGF in rats' serum were significantly elevated （P<0.01）， and the synovial Krenn score was increased （P<0.01）. The Mankin score of cartilage tissue was increased （P<0.01）， and the protein expressions of TRPV1 and p-p38 MAPK/p38 MAPK were significantly upregulated （P<0.01）. The experimental intervention significantly reduced the proportion of pro-inflammatory M1 macrophages in the total macrophage population （P<0.01）， and the percentage of M2 macrophages was decreased （P<0.01）. The M1/M2 macrophage ratio was significantly elevated （P<0.01）. Knee joint diameters of all dose groups of Huamoyan granules and the celecoxib group were reduced （P<0.01） compared with those of the model group， and the PPT recovery speeds in the high and medium-dose groups of Huamoyan granules were more obvious （P<0.05）. The contents of IL-1β， CGRP， and NGF in the rats' serum in all administration groups were significantly reduced （P<0.05， P<0.01）， and the content of TNF-α in rats' serum was significantly reduced （P<0.01）. All dose groups of Huamoyan granules demonstrated significant reductions in both synovial Krenn score （P<0.05， P<0.01） and protein expression of TRPV1 and p-p38 MAPK/p38 MAPK in rats' synovial tissues （P<0.01）. The percentage of M1 macrophages in the synovial tissues of the celecoxib group and all dose groups of Huamoyan granules was decreased （P<0.01）. The percentage of M2 macrophages was increased （P<0.05）， and the M1/M2 ratio was decreased （P<0.01）. ConclusionHuamoyan granules can alleviate the inflammatory response of KOA， reduce the release of inflammatory pain mediators， and downregulate TRPV1 protein expression by regulating macrophage polarization. Its mechanism may be related to the TRPV1/p38 MAPK signaling pathway， thereby achieving the effect of improving peripheral pain hypersensitivity in KOA.

To investigate the changes in peripheral blood immune cells before and after the onset of septic shock in patients with malignant tumors, and to analyze the relationship between these immune cells and patient prognosis.

OBJECTIVE To investigate the efficacy and safety of omadacycline in the treatment of macrolide-unresponsive Mycoplasma pneumoniae pneumonia （MUMPP） in children. METHODS A retrospective study was conducted on children aged 1-18 years old with MUMPP who were hospitalized in the Department of Pediatrics， the First Affiliated Hospital of Xinjiang Medical University from January 2022 to June 2025. According to the selection of secondary antibiotics after 72 h of initial treatment with macrolides， they were divided into the omadacycline group and the doxycycline group. Based on conventional treatment， children in the omadacycline group were given intravenous infusion of 2.4 mg/kg （once daily） of omadacycline tosylate， while children in the doxycycline group were given oral doxycycline hydrochloride tablets at 2 mg/kg （twice daily）. The efficacy and safety were compared between the two groups of pediatric patients. Univariate analysis and multivariate Logistic regression analysis were performed on clinical efficacy， and subgroup analysis along with multiple sensitivity analyses were conducted to verify the robustness of the conclusions. RESULTS A total of 284 children with MUMPP were included in this study， with 142 in the omadacycline group and 142 in the doxycycline group. In terms of efficacy， although the hospitalization time of children in the omadacycline group was longer than that in the doxycycline group （ P ＜0.05）， the lung lesion absorption rate and clinical efficacy were significantly higher or better than those in the doxycycline group （ P ＜0.05）. The results of multivariate Logistic regression analysis showed that medication （OR＝5.300， 95%CI： 2.526-11.123）， length of hospital stay （OR＝1.348， 95%CI： 1.167-1.556）， and medication duration （OR＝1.422， 95%CI： 1.169-1.729） were influencing factors of clinical efficacy （ P ＜0.05）. The subgroup analysis results showed that the clinical efficacy of omadacycline was significantly better than that of doxycycline in all subgroups （ P ＜0.05）. The results of multiple sensitivity analysis showed that the regression coefficients B of the four models （gradually adjust variables） before and after inverse probability of treatment weighting were significantly greater than 1 （ P ＜0.05）. In terms of safety， there was no statistically significant difference in the inci dence of adverse drug reactions between the two groups of patients （ χ 2 ＝0.447， P ＝0.504）. CONCLUSIONS In the case of hospitalization and prolonged medication， the efficacy of omadacycline in treating childhood MUMPP is superior to that of doxycycline， and its safety is good.

Radiotherapy is a crucial treatment modality for head and neck tumors. However, while effectively killing tumor cells, it significantly disrupts the homeostasis of the oral microecology, which is closely associated with various complications such as radiation-induced oral mucositis. Literature review indicates that as radiotherapy doses accumulate and treatment durations extend, the richness and diversity of the oral microbiota show a declining trend, with the genus Streptococcus decreasing most markedly. In contrast, radiotherapy selectively promotes the proliferation of bacterial phyla such as Proteobacteria and Bacteroidetes, which are rich in opportunistic pathogens. Mechanistically, radiotherapy activates the nuclear factor-kappa B pathway, triggering chronic inflammation and oxidative stress, damaging the epithelial barrier, suppressing local immunity, and causing damage to organs such as the salivary glands. It can also induce systemic diseases via the oral-gut axis, forming a multi-level, interconnected pathogenic network. In terms of interventions, treatment strategies including probiotics and prebiotics have shown promising efficacy against side effects such as radiation-induced oral mucositis. Saliva-based oral microbiota transplantation is an emerging strategy that is expected to become widely utilized for restoring oral microecological balance. Existing interventions provide preliminary pathways for clinical practice, but this field still faces several key scientific questions. The association between oral microecology and systemic diseases remains largely correlative, lacking causal evidence. Furthermore, critical parameters for oral microbiota transplantation, such as donor screening criteria, transplantation protocols, and long-term safety, are not yet well-defined. Therefore, future research should focus on conducting large-scale clinical trials to establish standardized protocols and safety evaluation systems for oral microecological interventions, and explore combined treatment therapies such as probiotics, prebiotics, and microbiota transplantation to advance the development of personalized precision modulation. These will enable more effective management of radiotherapy-induced oral microecological dysbiosis and improve treatment outcomes and quality of life for patients with head and neck tumors.

ObjectiveTo investigate the role of interleukin （IL）-17A in acute inhalational pneumonia induced by the highly drug-resistant and hypervirulent Staphylococcus aureus strain USA300-R in mice. MethodsAn acute inhalational pneumonia model was established in mice using an aerosolized pulmonary delivery technique. RNA sequencing （RNA-seq） and enzyme-linked immunosorbent assay （ELISA） were employed to examine the expression dynamics of Il17a mRNA and IL-17A protein， respectively， in the lungs of infected mice. Il17a knockout （Il17a^-/-） mice were generated using CRISPR/Cas9 gene editing technology. The survival rate， body weight， bacterial load in lung tissue， and histopathological changes were compared between Il17a^-/- and wild-type （WT） mice following inhalational infection with USA300-R. Results12 hours after USA300-R infection， compared to pre-infection， the expression level of Il17a mRNA in lung tissue and the level of IL-17A protein in bronchoalveolar lavage fluid （BALF） increased by approximately 50-fold （P<0.01） and 6-fold （P<0.001）， respectively. Compared to WT mice， Il17a^-/- mice exhibited approximately 10-fold higher bacterial loads in lung tissue at both 12 and 24 hours post-infection （P<0.001， P<0.05）. However， they showed significantly attenuated lung histopathological injury， reduced alveolar wall thickening， markedly decreased neutrophil infiltration， and an approximately 50% improvement in survival rate （P<0.05）. ConclusionIn acute Staphylococcus aureus USA300-R inhalational pneumonia， IL-17A contributes to bacterial clearance by recruiting neutrophils； however， excessive neutrophil infiltration exacerbates pulmonary inflammation and injury， reduces survival rates， and represents a potential therapeutic target.

Objective:To explore the specific mechanism of histone deacetylase 2(HDAC2)mediated histone H3 lysine 27 acetylation(H3K27ac)modification in promoting the proliferation and migration of hepatocellular carcinoma cells.Methods:Samples of 40 cases of hepatocellular carcinoma and paracan-cerous tissues resected from January 2021 to January 2023 were collected.The expressions of HDAC2 and H3K27ac in hepatocellular carcinoma,paracancerous tissues and cell lines were detected by immunohis-tochemistry and Western blotting.The correlation between the expression levels of HDAC2 and H3K27ac and the relationship between HDAC2 expression and clinicopathological characteristics of patients with hepatocellular carcinoma were analyzed.The proliferation,migration and invasion of Hep3B and HepG2 cells were determined by MTS,clone formation,scratch and Transwell experiments.The acetylation of H3K27 mediated by HDAC2 was verified by Western blotting,real-time fluorescence quantitative PCR(qRT-PCR)and chromatin immunoprecipitation high-throughput sequencing(ChIP-seq).In vivo xeno-transplantation experiment,the tumorigenicity of cells in each group was measured,and the expression of proteins related to phosphoinositide 3-kinases/phosphatase and tensin homolog deleted on chromosome ten/protein kinase B/mammalian target of rapamycin(PI3K/PTEN/AKT/mTOR)signal pathway was detected.Results:High expression of HDAC2 and low expression of H3K27ac were found in hepatocel-lular carcinoma tissues and cell lines(P＜0.05),and there was a negative correlation between them(r=-0.477,P=0.002).The expression of HDAC2 was related to tumor size,hepatitis B virus infec-tion,TNM stage and portal vein tumor thrombus(P＜0.05).Compared with the sh-NC group of Hep3B and HepG2 cells,the proliferation,clone formation,migration and invasion ability of sh-HDAC2 group were decreased(P＜0.05).Compared with the Empty group,the HDAC2 group exhibited increased ex-pression levels and activity of HDAC2,as well as enhanced cell proliferation,clone formation,migra-tion,invasion ability,tumor volume and mass in vivo,and elevated expression levels of p-PI3K,p-AKT,and p-mTOR(P＜0.05).Conversely,the enrichment and expression levels of H3K27ac,along with the expression level of PTEN,were decreased(P＜0.05).In the iHDAC2 group,the expression levels and activity of HDAC2,as well as the proliferation,clone formation,migration,invasion ability,tumor volume and mass in vivo,and expression levels of p-PI3K,p-AKT,and p-mTOR were reduced(P＜0.05).Additionally,the expression levels of H3K27ac and PTEN were increased(P＜0.05).To validate the involvement of the PI3K/PTEN/AKT/mTOR signaling pathway in HDAC2-mediated regula-tion of malignant behaviors in liver cancer cells through H3K27ac,the PI3K activator 740Y-P was intro-duced.Compared with the iHDAC2 group,the iHDAC2+740Y-P group exhibited increased prolifera-tion,clone formation,migration,invasion ability,tumor volume and mass in vivo,and elevated expres-sion levels of p-PI3K,p-AKT,and p-mTOR(P＜0.05).Conversely,the expression level of PTEN was decreased(P＜0.05).Conclusion:HDAC2 initiates PI3K/PTEN/AKT/mTOR signal pathway by me-diating H3K27 acetylation,which promotes the occurrence and development of hepatocellular carcinoma.

Objective To investigate the influence of combination of oxycodone-acetaminophen and local radiotherapy on serum cytokines in elderly patients with malignant tumor bone metastasis and cancer pain.Methods Eighty elderly patients with malignant tumor bone metastasis and cancer pain admitted to Huainan Xinhua Medical Group Xinhua Hospital from January 2020 to April 2024 were divided into control group(40 cases)and observa-tion group(40 cases)according to the order of admission.The control group received codeine combined with local radiotherapy,whereas the observation group was treated with oxycodone-acetaminophen combined with local radio-therapy.Pain relief(assessed using visual analogue scale(VAS)),daily fulminant pain occurrence frequency and occurrence of adverse reactions during treatment as well as serum cytokines[substance P(SP),prostaglandinE2(PGE2),interleukin-6(IL-6)],sleep quality(assessed using Pittsburgh sleep quality index(PSQI))and quality of life[assessed using functional assessment of cancer therapy-general(FACT-G)]before and after treatment were compared between the two groups..Results The pain relief effect in the observation group was better(P<0.05),and the daily occurrence frequency of fulminant pain was less than that in the control group(P<0.05).After treat-ment,serum levels of SP,PGE2 and IL-6 in the observation group were lower compared to those in the control group(P<0.05).The total incidence rate of bone-related events during treatment was not significantly different between the two groups(P>0.05),and the total incidence rate of adverse reactions was lower in the observation group compared to those in the control group(P<0.05).The PSQI score in the observation group after treatment was lower(P<0.05)while the scores of physiology and emotion of FACT-G were higher compared to those in the control group(P<0.05).Conclusion Oxycodone-acetaminophen combined with local radiotherapy can down-regulate the levels of serum SP,PGE2 and IL-6,relieve the pain,and improve the sleep quality and quality of life in elderly patients with malignant tumor bone metastasis complicated with cancer pain.

Objective To analyze the potential biological relationship between Alzheimer disease(AD)and chronic periodontitis(CP)by bioinformatics.Methods We analyzed two datasets of AD and CP from the Gene Expression Omnibus database,and differentially expressed genes(DEGs)were identified from these datasets.Weighted gene co-expression network analysis(WGCNA)was used to identify the most relevant modules.Functional enrichment analysis of shared genes was performed,and a protein-protein interaction(PPI)network was constructed.MCODE was used to identify key modules,and machine learning was used to discover key genes.In addition,Gene Set Enrichment Analysis(GSEA)and CIBERSORT were used to investigate KLRB1-related molecular pathways and immune cell distribu-tion.Results The study identified 18 genes common to both AD and CP.MCODE analysis revealed five pivotal genes,machine learning identified 13 genes for AD,eight for CP,and KLRB1 was determined as a common gene for AD and CP.GSEA demonstrated the intricate involvement of these genes in disease-related pathways.Immunocellular analysis underscored a significant association between KLRB1 and γδT cells.Conclusion This research highlighted KLRB1 as a key gene for AD and CP,providing new insights into their molecular linkages.