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.

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.

BACKGROUND:Copper is an essential trace element and plays a key role in series of physiological activities in the body.Metabolic disturbance of copper is closely associated with multiple diseases.Copper metabolism is mainly involved in the absorption,transport,storage and excretion of copper ions,and all the above processes regulate copper homeostasis in the body.In recent years,many studies have confirmed that copper homeostasis disorder severely affects the metabolic activities of the body and cause diseases in various systems.Besides,the role of copper in oral diseases has been of great interest.OBJECTIVE:To explore the role of copper in occurrence,development,and treatment of oral diseases,and provide a comprehensive overview of research advances in this field.METHODS:The first author searched relevant studies on copper in oral diseases using a computer in PubMed,Web of Science,and CNKI.The key words were"Cu,copper,copper metabolism,oral diseases,oral squamous cell carcinoma,periodontitis,oral submucous fibrosis,oral lichen planus,recurrent oral ulceration,pultitis"in English and Chinese.After screening,78 articles were included for further review and analysis.RESULTS AND CONCLUSION:(1)Patients with oral squamous cell carcinoma have elevated concentrations of copper in serum and saliva,and elevated copper promotes cancer progression through oxidative stress and promoting angiogenesis.Excessive elevation or reduction of copper concentration in tumor cells can inhibit the growth of tumor cells.The combination of copper and anticancer drugs can significantly improve the efficacy of drugs.(2)The concentration of copper in the serum of patients with periodontitis is increased,and excessive copper can aggravate periodontitis through promoting oxidative stress.Combination of copper and drugs can promote periodontal bone regeneration and periodontal tissue healing.(3)The level of copper is positively correlated with degree of oral mucosa fibrosis.Copper that enters the oral mucosa promotes fibrosis of oral mucosa by enhancing activity of lysyloxidase to increase production of collagen.(4)Copper levels are elevated in patients with oral lichen planus,and elevated copper may promote the progression of oral lichen planus by modulating immune cell function.(5)In patients with recurrent oral ulcers,serum copper level is significantly increased,and utilization of copper becomes disordered,which could decrease copper-containing enzyme activity,thus affecting the healing of ulcers.Copper is closely associated with multiple oral diseases and therapies targeting at copper could obviously enhance the therapeutic effect of drugs.But further studies are still needed to uncover its mechanisms to lay foundation for the better treatment of oral diseases.

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 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.

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.

BACKGROUND:Copper is an essential trace element and plays a key role in series of physiological activities in the body.Metabolic disturbance of copper is closely associated with multiple diseases.Copper metabolism is mainly involved in the absorption,transport,storage and excretion of copper ions,and all the above processes regulate copper homeostasis in the body.In recent years,many studies have confirmed that copper homeostasis disorder severely affects the metabolic activities of the body and cause diseases in various systems.Besides,the role of copper in oral diseases has been of great interest.OBJECTIVE:To explore the role of copper in occurrence,development,and treatment of oral diseases,and provide a comprehensive overview of research advances in this field.METHODS:The first author searched relevant studies on copper in oral diseases using a computer in PubMed,Web of Science,and CNKI.The key words were"Cu,copper,copper metabolism,oral diseases,oral squamous cell carcinoma,periodontitis,oral submucous fibrosis,oral lichen planus,recurrent oral ulceration,pultitis"in English and Chinese.After screening,78 articles were included for further review and analysis.RESULTS AND CONCLUSION:(1)Patients with oral squamous cell carcinoma have elevated concentrations of copper in serum and saliva,and elevated copper promotes cancer progression through oxidative stress and promoting angiogenesis.Excessive elevation or reduction of copper concentration in tumor cells can inhibit the growth of tumor cells.The combination of copper and anticancer drugs can significantly improve the efficacy of drugs.(2)The concentration of copper in the serum of patients with periodontitis is increased,and excessive copper can aggravate periodontitis through promoting oxidative stress.Combination of copper and drugs can promote periodontal bone regeneration and periodontal tissue healing.(3)The level of copper is positively correlated with degree of oral mucosa fibrosis.Copper that enters the oral mucosa promotes fibrosis of oral mucosa by enhancing activity of lysyloxidase to increase production of collagen.(4)Copper levels are elevated in patients with oral lichen planus,and elevated copper may promote the progression of oral lichen planus by modulating immune cell function.(5)In patients with recurrent oral ulcers,serum copper level is significantly increased,and utilization of copper becomes disordered,which could decrease copper-containing enzyme activity,thus affecting the healing of ulcers.Copper is closely associated with multiple oral diseases and therapies targeting at copper could obviously enhance the therapeutic effect of drugs.But further studies are still needed to uncover its mechanisms to lay foundation for the better treatment of oral diseases.

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.