BACKGROUND:During diabetic wound healing,the sustained activation of M1 macrophages exacerbates the inflammatory response and hinders wound repair.Auranofin,an anti-inflammatory drug,has not been clearly studied for its effects on M1 macrophages and its potential role in diabetic wound healing.OBJECTIVE:To investigate the effects of different concentrations of auranofin on the biological function of M1 macrophages and evaluate its potential application in diabetic wound healing.METHODS:RAW264.7 and THP-1 cells were used as research models.M1 polarization was induced using different concentrations of interferon-γ and lipopolysaccharide.M1 macrophages were treated with 1 and 2 μmol/L auranofin.Cell counting kit-8 assay was used to evaluate the effect of auranofin on cell viability.Quantitative real-time PCR was performed to detect mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.ELISA was employed to measure the levels of interleukin-1β,interleukin-6,and tumor necrosis factor-α in the supernatant.Western blot analysis was used to assess the expression of nuclear factor-κB(p65),phosphorylated mitogen-activated protein kinases(MAPK),and total MAPK proteins.Additionally,6-8-week-old male C57BL/6J and db/db diabetic mice were used for wound healing experiments,with the mice divided into C57 control,db/db control and auranofin treatment groups,each containing six animals.Dorsal skin defect modeling and treatment with intraperitoneal injection of auranofin were performed to observe wound healing in mice.RESULTS AND CONCLUSION:(1)Cell experiments showed that co-treatment with interferon-y(10 ng/mL)and lipopolysaccharide(100 ng/mL)significantly induced M1 polarization in RAW264.7 and THP-1 cells,resulting in increased mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.Treatment with auranofin(1 and 2 μmol/L)reduced the mRNA expression of these inflammatory factors in the cells and inhibited the secretion of inflammatory factors in the cell supernatant.(2)Auranofin treatment significantly suppressed the activation of nuclear factor-κB(p65)and phosphorylated MAPK signaling pathways.(3)Animal experiments showed that auranofin promoted wound healing in db/db diabetic mice,suggesting that auranofin has strong anti-inflammatory effects and may facilitate the healing of wounds in diabetic mice.

BACKGROUND:During diabetic wound healing,the sustained activation of M1 macrophages exacerbates the inflammatory response and hinders wound repair.Auranofin,an anti-inflammatory drug,has not been clearly studied for its effects on M1 macrophages and its potential role in diabetic wound healing.OBJECTIVE:To investigate the effects of different concentrations of auranofin on the biological function of M1 macrophages and evaluate its potential application in diabetic wound healing.METHODS:RAW264.7 and THP-1 cells were used as research models.M1 polarization was induced using different concentrations of interferon-γ and lipopolysaccharide.M1 macrophages were treated with 1 and 2 μmol/L auranofin.Cell counting kit-8 assay was used to evaluate the effect of auranofin on cell viability.Quantitative real-time PCR was performed to detect mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.ELISA was employed to measure the levels of interleukin-1β,interleukin-6,and tumor necrosis factor-α in the supernatant.Western blot analysis was used to assess the expression of nuclear factor-κB(p65),phosphorylated mitogen-activated protein kinases(MAPK),and total MAPK proteins.Additionally,6-8-week-old male C57BL/6J and db/db diabetic mice were used for wound healing experiments,with the mice divided into C57 control,db/db control and auranofin treatment groups,each containing six animals.Dorsal skin defect modeling and treatment with intraperitoneal injection of auranofin were performed to observe wound healing in mice.RESULTS AND CONCLUSION:(1)Cell experiments showed that co-treatment with interferon-y(10 ng/mL)and lipopolysaccharide(100 ng/mL)significantly induced M1 polarization in RAW264.7 and THP-1 cells,resulting in increased mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.Treatment with auranofin(1 and 2 μmol/L)reduced the mRNA expression of these inflammatory factors in the cells and inhibited the secretion of inflammatory factors in the cell supernatant.(2)Auranofin treatment significantly suppressed the activation of nuclear factor-κB(p65)and phosphorylated MAPK signaling pathways.(3)Animal experiments showed that auranofin promoted wound healing in db/db diabetic mice,suggesting that auranofin has strong anti-inflammatory effects and may facilitate the healing of wounds in diabetic mice.

POEMS syndrome is a rare condition associated with plasma cell disorders， and it often involves multiple systems and has diverse clinical manifestations. This article reports two cases of POEMS syndrome with hepatosplenomegaly as the initial manifestation. During the course of the disease， the patients presented with lower limb weakness， hepatosplenomegaly， lymph node enlargement， ascites， hypothyroidism， positive M protein， and skin hyperpigmentation， and ¹⁸F-FDG PET-CT imaging revealed bone lesions mainly characterized by osteolytic changes and plasma cell tumors. There was an increase in the serum level of vascular endothelial growth factor. The patients were finally diagnosed with POEMS syndrome， and the symptoms were relieved after immunomodulatory treatment.

Objective:To investigate the related factors of cognitive impairment in middle-aged and old-aged patients with type 2 diabetes mellitus(T2DM).Methods:A total of 970 patients with T2DM(585 middle-aged group and 385 old-aged group)were selected from residents of a large community in Beijing from September to December 2018.The Mini-Mental State Examination(MMSE)was used to assess the cognitive func-tion.Multivariate logistic regression was used to analyze the related factors.Results:The detection rates of cognitive impairment were 12.0％and 13.5％in middle-aged and old-aged patients with T2DM,respectively.Among mid-dle-aged patients with T2DM,work(OR=0.22,95％CI:0.03-0.77)and education at the junior college or un-dergraduate level and above(OR=0.18,95％CI:0.04-0.55)were protective factors for cognitive impair-ment.Myocardial infarction(OR=4.13,95％CI:1.26-13.63)was a risk factor for cognitive impairment.Among old-aged patients with T2DM,drinking tea 1-2 times a week(OR=0.11,95％CI:0.01-0.58)and education at the junior college or undergraduate level and above(OR=0.19,95％CI:0.05-0.54)were protective factors for cognitive impairment.Stroke(OR=3.64,95％CI:1.55-8.39)and good sleep self-assessment(OR=2.75,95％CI:1.13-7.35)were risk factors for cognitive impairment.Conclusion:Cognitive impairment in middle-aged pa-tients with T2DM is related to work,education level and myocardial infarction,and cognitive impairment in old-aged patients with T2DM is related to lifestyle,education level and stroke.

Objective:To investigate the related factors of cognitive impairment in middle-aged and old-aged patients with type 2 diabetes mellitus(T2DM).Methods:A total of 970 patients with T2DM(585 middle-aged group and 385 old-aged group)were selected from residents of a large community in Beijing from September to December 2018.The Mini-Mental State Examination(MMSE)was used to assess the cognitive func-tion.Multivariate logistic regression was used to analyze the related factors.Results:The detection rates of cognitive impairment were 12.0％and 13.5％in middle-aged and old-aged patients with T2DM,respectively.Among mid-dle-aged patients with T2DM,work(OR=0.22,95％CI:0.03-0.77)and education at the junior college or un-dergraduate level and above(OR=0.18,95％CI:0.04-0.55)were protective factors for cognitive impair-ment.Myocardial infarction(OR=4.13,95％CI:1.26-13.63)was a risk factor for cognitive impairment.Among old-aged patients with T2DM,drinking tea 1-2 times a week(OR=0.11,95％CI:0.01-0.58)and education at the junior college or undergraduate level and above(OR=0.19,95％CI:0.05-0.54)were protective factors for cognitive impairment.Stroke(OR=3.64,95％CI:1.55-8.39)and good sleep self-assessment(OR=2.75,95％CI:1.13-7.35)were risk factors for cognitive impairment.Conclusion:Cognitive impairment in middle-aged pa-tients with T2DM is related to work,education level and myocardial infarction,and cognitive impairment in old-aged patients with T2DM is related to lifestyle,education level and stroke.

Objective:To explore the influencing factors of the therapeutic effect of fiberoptic bronchoscopic alveolar lavage (BAL) in children with severe pneumonia (SP), and the relationship between pulmonary ultrasound parameters and the clearance rates of procalcitonin (PCT) and C-reactive protein (CRP) after treatment.Methods:A total of 284 children with SP admitted to the Yan ′an People′s Hospital from February 2019 to October 2023 were selected as the research subjects; According to the prognosis after 30 days of treatment, they were divided into the good prognosis group ( n=213) and the poor prognosis group ( n=71). The changes of PCT clearance rate, CRP clearance rate and Lung Ultrasound Score (LUS) before and after treatment were compared between the two groups. The correlation between indexes was analyzed using the multiple linear regression (MLR) model. The odds ratio ( OR) of risk factors was calculated using the multivariate logistic regression model. The dose-response relationship was evaluated using the restricted cubic spline (RCS) model. The receiver operating characteristic (ROC) curve was used to analyze the predicting value of each index for poor prognosis after 30 days of treatment. Results:Compared with the good prognosis group, the CRP clearance rate and PCT clearance rate of children in the poor prognosis group were lower 7-14 days after treatment (all P<0.05), and the LUS was higher (all P<0.05). The MLR analysis results showed that LUS was negatively correlated with both CRP clearance rate and PCT clearance rate (all P<0.05), and there was still a significant correlation after adjusting for confounding factors (all P<0.05). The results of logistic regression analysis showed that after excluding confounding factors (Model 4), LUS, PCT clearance rate, and CRP clearance rate were independent risk factors for poor prognosis in children with SP after 30 days of treatment (all P<0.05). The results of RCS analysis showed that there was a nonlinear relationship between the continuous changes of LUS, PCT clearance rate and CRP clearance rate and the risk of poor prognosis in children with SP after 30 days of treatment (nonlinear tests all P<0.001). The combined accuracy of LUS, PCT clearance rate and CRP clearance rate in predicting the poor prognosis of children with SP after 30 days of treatment was relatively high ( P<0.05, AUC>0.75). Conclusions:The clearance rates of LUS and CRP, as well as PCT, are all associated with poor prognosis in children with SP, and the decreased clearance rates of CRP and PCT are independent factors for predicting the increase of LUS. The combined clearance rates of LUS and CRP, as well as PCT, can accurately predict the risk of poor prognosis in children.

Objective:To explore the influencing factors of the therapeutic effect of fiberoptic bronchoscopic alveolar lavage (BAL) in children with severe pneumonia (SP), and the relationship between pulmonary ultrasound parameters and the clearance rates of procalcitonin (PCT) and C-reactive protein (CRP) after treatment.Methods:A total of 284 children with SP admitted to the Yan ′an People′s Hospital from February 2019 to October 2023 were selected as the research subjects; According to the prognosis after 30 days of treatment, they were divided into the good prognosis group ( n=213) and the poor prognosis group ( n=71). The changes of PCT clearance rate, CRP clearance rate and Lung Ultrasound Score (LUS) before and after treatment were compared between the two groups. The correlation between indexes was analyzed using the multiple linear regression (MLR) model. The odds ratio ( OR) of risk factors was calculated using the multivariate logistic regression model. The dose-response relationship was evaluated using the restricted cubic spline (RCS) model. The receiver operating characteristic (ROC) curve was used to analyze the predicting value of each index for poor prognosis after 30 days of treatment. Results:Compared with the good prognosis group, the CRP clearance rate and PCT clearance rate of children in the poor prognosis group were lower 7-14 days after treatment (all P<0.05), and the LUS was higher (all P<0.05). The MLR analysis results showed that LUS was negatively correlated with both CRP clearance rate and PCT clearance rate (all P<0.05), and there was still a significant correlation after adjusting for confounding factors (all P<0.05). The results of logistic regression analysis showed that after excluding confounding factors (Model 4), LUS, PCT clearance rate, and CRP clearance rate were independent risk factors for poor prognosis in children with SP after 30 days of treatment (all P<0.05). The results of RCS analysis showed that there was a nonlinear relationship between the continuous changes of LUS, PCT clearance rate and CRP clearance rate and the risk of poor prognosis in children with SP after 30 days of treatment (nonlinear tests all P<0.001). The combined accuracy of LUS, PCT clearance rate and CRP clearance rate in predicting the poor prognosis of children with SP after 30 days of treatment was relatively high ( P<0.05, AUC>0.75). Conclusions:The clearance rates of LUS and CRP, as well as PCT, are all associated with poor prognosis in children with SP, and the decreased clearance rates of CRP and PCT are independent factors for predicting the increase of LUS. The combined clearance rates of LUS and CRP, as well as PCT, can accurately predict the risk of poor prognosis in children.

Objective To evaluate the effectiveness and safety of Su Fei He Ji combined with anlotinib hydrochloride in the treatment of refractory advanced non-small cell lung cancer(NSCLC)patients presenting with phlegm stasis obstructing lung type.Methods Thirty-nine patients with advanced NSCLC were randomly assigned to either a control group(19 patients)or an experimental group(20 patients).The control group received treatment with anlotinib alone,while the experimental group received an additional oral administration of Su Fei He Ji.A comparative analysis was conducted between the two groups based on various parameters including short-term objective therapeutic efficacy,progression-free survival,TCM syndrome scores,KPS scores,weight changes,related tumor markers,incidence of adverse reactions,and variations in plasma concentrations of anlotinib.Results Following treatment,the objective response rate was 5%and the disease control rate was 85%in the experimental group,while the control group showed an objective response rate of 0%and a disease control rate of 78.95%.No statistically significant difference was observed in short-term objective efficacy between the two groups(P>0.05).Notably,the experimental group exhibited a significant improvement compared to the control group in various aspects,including TCM syndrome scores and KPS scores(P<0.05).Conversely,no significant differences were observed in weight changes or the reduction levels of other tumor markers(CEA,SCC,CA125,CA199,CYFRA21-1)(P>0.05).Moreover,the incidence of fatigue was notably lower in the experimental group(P<0.05),while no statistical difference was evident in the occurrence of other adverse reactions,such as hypertension,rash,and bleeding,between the two groups(P>0.05).It is important to highlight that there was no statistically significant variance in plasma concentrations between the groups(P>0.05),and no significant correlation was identified between plasma concentrations and the incidence of adverse reactions(P>0.05).Conclusion The combination of Su Fei He Ji and anlotinib hydrochloride effectively improves clinical symptoms and quality of life,and reduces adverse reactions in advanced NSCLC patients.This is achieved without affecting the plasma concentrations of anlotinib.

Smoking is a well-established risk factor for periodontitis, yet the precise mechanisms by which smoking contributes to periodontal disease remain poorly understood. Recent advances in spatial transcriptomics have enabled a deeper exploration of the periodontal tissue microenvironment at single-cell resolution, offering new opportunities to investigate these mechanisms. In this study, we utilized Visium HD single-cell spatial transcriptomics to profile gingival tissues from 12 individuals, including those with periodontitis, those with smoking-associated periodontitis, and healthy controls. Our analysis revealed that smoking disrupts the epithelial barrier integrity, induces fibroblast alterations, and dysregulates fibroblast-epithelial cell communication, thereby exacerbating periodontitis. The spatial analysis showed that endothelial cells and macrophages are in close proximity and interact, which further promotes the progression of smoking-induced periodontal disease. Importantly, we found that targeting the endothelial CXCL12 signalling pathway in smoking-associated periodontitis reduced the proinflammatory macrophage phenotype, alleviated epithelial inflammation, and reduced alveolar bone resorption. These findings provide novel insights into the pathogenesis of smoking-associated periodontitis and highlight the potential of targeting the endothelial-macrophage interaction as a therapeutic strategy. Furthermore, this study establishes an essential information resource for investigating the effects of smoking on periodontitis, providing a foundation for future research and therapeutic development for this prevalent and debilitating disease.
Humans ; Gingiva/cytology* ; Smoking/adverse effects* ; Male ; Periodontitis/pathology* ; Single-Cell Analysis ; Female ; Adult ; Middle Aged ; Macrophages ; Fibroblasts ; Endothelial Cells ; Case-Control Studies ; Chemokine CXCL12/metabolism*

Objective: To investigate the molecular mechanisms and pathways of action of total flavonoids of Dracocephalum moldavica L.(TFDM) in treating vascular cognitive impairment(VCI) based on network pharmacology and in vivo animal experiments. Methods : The swiss target prediction database, literature, and PubChem were used to screen the active components and action targets of TFDM. The online mendelian inheritance in man(OMIM) and GeneCards databases were utilized to screen for possible VCI targets. Venny software was used to obtain the intersection target of TFDM and VCI. The search tool for recurring instances of neighbouring genes(String) database and Cytoscape software was used to construct the PPI network. The database for annotation, visualization and integrated discovery(DAVID) database was utilized to screen for the kyoto encyclopedia of genes and genomes(KEGG) pathway and gene ontology(GO) enrichment analyses to explore the molecular mechanism and signaling pathway of TFDM for VCI. 24 rats were divided into Sham, Model, Donepezil, and TFDM groups. Except for the Sham group, the VCI model was created using modified bilateral common carotid artery ligation. After continuous gavage for 21 days, the Morris water maze test was used to evaluate the spatial learning and memory ability of rats. Hematoxy-lineosin(HE) staining was used to observe the pathological changes in the hippocampal CA1 and cortex region of the animals and immunohistochemistry detection of zonula occludens-1(ZO-1) content in the brains of the rats. Western blot was used to detect nuclear factor kappa-B p65(NF-κB p65) and tumor necrosis factor-α(TNF-α) in rat brains. Results : A total of 39 active ingredients of TFDM were screened, 209 corresponding targets, 10 417 gene targets of VCI, and 193 intersecting targets. According to the results of the GO enrichment of function analysis, TFDM could improve the response of reactive oxygen species and metabolic processes of reactive oxygen species, etc. KEGG pathway enrichment analysis suggested that TFDM might regulate TNF, IL-17 signing pathway, etc. The results of animal experiments showed that TFDM improved learning and memory while reduced pathological damage in the brains of VCI rats. In addition, TFDM upregulated the positive expression of ZO-1 and downregulated the protein levels of TNF-α and NF-κB p65(P<0.05). Conclusion TFDM can improve the cognitive function of VCI through multi-components and multi-targets, and its key mechanism may be related to inhibiting TNF-α/NF-κB p65 signaling pathway,reducing neuroinflammation,and improvement of blood-brain barrier permeability.