AIM:To investigate the regulatory role and molecular mechanisms of the p62-NIMA(never in mi-tosis gene A)-related kinase 7(NEK7)-gasdermin D(GSDMD)-mediated pyroptosis axis in a mouse model of gouty arthri-tis.METHODS:C57BL/6 mice were randomly divided into control group,model group,and colchicine group(n=5 per group).Conditional knockout mouse models of p62,GSDMD,and p62-GSDMD were constructed and assigned to p62-/-group,GSDMD-/-group,and p62-/--GSDMD-/-group,respectively(n=5 per group).The gouty arthritis model was in-duced by monosodium urate crystal injection into the ankle joint in all groups except control.The colchicine group re-ceived oral colchicine pretreatment for 3 days prior to MSU injection,continuing for 5 days total.Ankle joint swelling was measured using a vernier caliper at 0,6,12,24,and 48 hours post-injection.Serum levels of p62,GSDMD,caspase-1,interleukin-1β(IL-1β),and IL-18 were quantified by ELISA.Immunohistochemistry staining was performed to assess nu-cleotide-binding oligomerization domain-like receptor protein 3(NLRP3),apoptosis-associated speck-like protein contain-ing a caspase recruitment domain(ASC),cleaved caspase-1,and IL-1β expression in joint tissues.Western blot was con-ducted to detect protein expression of p62,GSDMD,NLRP3,ASC,cleaved caspase-1,and IL-1β in mouse ankle joints,while RT-qPCR was used to measure mRNA expression of p62,NEK7,GSDMD,NLRP3,caspase-1 and IL-1β.RE-SULTS:Serum p62 levels and p62 protein and mRNA expression in ankle joints were significantly elevated in the model group.Following p62 gene knockout,the protein expression of NLRP3,ASC,caspase-1,and IL-1β in ankle joints showed a marked increase.Both GSDMD-/-and p62-/--GSDMD-/-groups exhibited attenuated ankle joint swelling,reduced serum levels of caspase-1,IL-1β,and IL-18,along with downregulated expression of p62,NLRP3,ASC,caspase-1,and IL-1β at both mRNA and protein levels in ankle joints.The NEK7 mRNA expression was similarly suppressed in these groups.CONCLUSION:Our findings demonstrate that MSU crystals activate macrophages through the coordinated action of p62,NEK7,and GSDMD,triggering NLRP3 inflammasome-mediated pyroptosis and ultimately promoting joint inflammation in gout mice.The p62-NEK7-GSDMD axis represents a critical regulatory mechanism in the canonical pyrop-tosis signaling pathway.

AIM:To investigate the regulatory role and molecular mechanisms of the p62-NIMA(never in mi-tosis gene A)-related kinase 7(NEK7)-gasdermin D(GSDMD)-mediated pyroptosis axis in a mouse model of gouty arthri-tis.METHODS:C57BL/6 mice were randomly divided into control group,model group,and colchicine group(n=5 per group).Conditional knockout mouse models of p62,GSDMD,and p62-GSDMD were constructed and assigned to p62-/-group,GSDMD-/-group,and p62-/--GSDMD-/-group,respectively(n=5 per group).The gouty arthritis model was in-duced by monosodium urate crystal injection into the ankle joint in all groups except control.The colchicine group re-ceived oral colchicine pretreatment for 3 days prior to MSU injection,continuing for 5 days total.Ankle joint swelling was measured using a vernier caliper at 0,6,12,24,and 48 hours post-injection.Serum levels of p62,GSDMD,caspase-1,interleukin-1β(IL-1β),and IL-18 were quantified by ELISA.Immunohistochemistry staining was performed to assess nu-cleotide-binding oligomerization domain-like receptor protein 3(NLRP3),apoptosis-associated speck-like protein contain-ing a caspase recruitment domain(ASC),cleaved caspase-1,and IL-1β expression in joint tissues.Western blot was con-ducted to detect protein expression of p62,GSDMD,NLRP3,ASC,cleaved caspase-1,and IL-1β in mouse ankle joints,while RT-qPCR was used to measure mRNA expression of p62,NEK7,GSDMD,NLRP3,caspase-1 and IL-1β.RE-SULTS:Serum p62 levels and p62 protein and mRNA expression in ankle joints were significantly elevated in the model group.Following p62 gene knockout,the protein expression of NLRP3,ASC,caspase-1,and IL-1β in ankle joints showed a marked increase.Both GSDMD-/-and p62-/--GSDMD-/-groups exhibited attenuated ankle joint swelling,reduced serum levels of caspase-1,IL-1β,and IL-18,along with downregulated expression of p62,NLRP3,ASC,caspase-1,and IL-1β at both mRNA and protein levels in ankle joints.The NEK7 mRNA expression was similarly suppressed in these groups.CONCLUSION:Our findings demonstrate that MSU crystals activate macrophages through the coordinated action of p62,NEK7,and GSDMD,triggering NLRP3 inflammasome-mediated pyroptosis and ultimately promoting joint inflammation in gout mice.The p62-NEK7-GSDMD axis represents a critical regulatory mechanism in the canonical pyrop-tosis signaling pathway.

Objective To analyze the clinical characteristics and factors influencing adverse treatment outcomes in elderly patients with multidrug-resistant pulmonary tuberculosis (MDR-TB) to guide the clinical diagnosis and treatment of elderly MDR-TB patients. Methods Clinical data of elderly patients with multidrug-resistant pulmonary tuberculosis initially treated at Beijing Chest Hospital from 2008 to 2023 were retrospectively collected. Complications/comorbidities, adverse drug reactions, drug resistance during initial treatment, and retreatment were statistically described. Factors influencing adverse treatment outcomes were analyzed using the chi-square test and logistic regression analysis. Results A total of 238 elderly patients with MDR-TB were collected, of which 152 (63.9%) had adverse drug reactions, 184 (77.3%) were retreated MDR-TB, 27 (11.3%) were extensively drug-resistant tuberculosis (XDR-TB), 41 were cured, 6 completed treatment, 39 failed treatment, 6 died, 107 lost to follow-up, 31 could not be evaluated, 8 did not finish treatment, and the treatment success rate was 20.4% (47/230). The adverse outcome of treatment accounted for 79.6% (183/230). Univariate analysis showed that differences in age groups, the occurrence of drug adverse reactions, and patient sources had a statistically significant impact on treatment outcomes (P<0.05). Logistic regression analysis was performed using good and adverse treatment outcomes as dependent variables for the three factors, which showed that being aged 70 and above, the occurrence of drug adverse reactions during treatment, and being a non-local patient were factors influencing adverse treatment outcomes [OR (95%CI): 2.507 (1.027-6.121), 3.253 (1.635-6.473), 2.563 (1.285-5.111), respectively]. Conclusions Elderly patients with MDR-TB exhibit a high prevalence of complications/comorbidities, a high incidence of drug adverse reactions, and unfavorable treatment outcomes. Out-of-town medical treatment, advanced age, and experiencing drug adverse reactions are risk factors for adverse treatment outcomes.

Objective To summarize the clinical characteristics of delayed diagnosis of tuberculosis in children,analyze the risk factors of delayed diagnosis,and support early diagnosis of tuberculosis in children.Methods This is a retrospective analysis based on the clinical data of tuberculosis patients admitted to the Children's Hospital Affiliated to Zhengzhou University from January 2015 to February 2023.The clinical characteristics of children were analyzed in terms of age group.According to the definition of diagnosis delay,the patients were assigned to delayed group and non-delayed group.Univariate analysis and multivariate logistic regression were used to analyze the risk factors for diagnosis delay.Results A total of 82 children with tuberculosis were included(46 cases in delayed diagnosis group and 36 cases in non-delayed diagnosis group).The rate of diagnosis delay was 56.1％.The incidence of acute miliary pulmonary tuberculosis and tuberculous meningitis was significantly higher in children ≤5 years old than that in children＞5 years old(P＜0.05).Diagnosis delay was associated with significantly higher prevalence of chronic fever,cough＞2 weeks,growth retardation and significantly longer duration of empirical antibiotic use compared to the children without diagnosis delay(P＜0.05).Univariate analysis showed that patient origin,contact history,mixed infection,tuberculosis type,molecular biological assay and severe disease were related to the delay of TB diagnosis(P＜0.05).Multivariate logistic regression analysis showed that patient origin[≥3 clinic visits(OR=7.064,95％CI:1.677-29.754)],mixed infection(OR=3.812,95％CI:1.185-12.260),severe disease(OR=3.697,95％CI:1.081-12.646)]were risk factors for diagnosis delay in children.Molecular biological assay(OR=4.642,95％CI:1.318-16.345)was a protective factor.Conclusions The clinical symptoms of tuberculosis in children are atypical.Delayed diagnosis of tuberculosis is common.Multiple clinic visits,mixed infection,and severe disease are the risk factors for diagnosis delay.Tuberculosis should be taken into account for the children with chronic fever,cough and growth retardation who have failed to respond to adequate therapy with third-generation cephalosporin and carbapenems.Molecular biological assay is helpful for early diagnosis of tuberculosis in children with negative sputum smear.

Objective To summarize the clinical characteristics of delayed diagnosis of tuberculosis in children,analyze the risk factors of delayed diagnosis,and support early diagnosis of tuberculosis in children.Methods This is a retrospective analysis based on the clinical data of tuberculosis patients admitted to the Children's Hospital Affiliated to Zhengzhou University from January 2015 to February 2023.The clinical characteristics of children were analyzed in terms of age group.According to the definition of diagnosis delay,the patients were assigned to delayed group and non-delayed group.Univariate analysis and multivariate logistic regression were used to analyze the risk factors for diagnosis delay.Results A total of 82 children with tuberculosis were included(46 cases in delayed diagnosis group and 36 cases in non-delayed diagnosis group).The rate of diagnosis delay was 56.1％.The incidence of acute miliary pulmonary tuberculosis and tuberculous meningitis was significantly higher in children ≤5 years old than that in children＞5 years old(P＜0.05).Diagnosis delay was associated with significantly higher prevalence of chronic fever,cough＞2 weeks,growth retardation and significantly longer duration of empirical antibiotic use compared to the children without diagnosis delay(P＜0.05).Univariate analysis showed that patient origin,contact history,mixed infection,tuberculosis type,molecular biological assay and severe disease were related to the delay of TB diagnosis(P＜0.05).Multivariate logistic regression analysis showed that patient origin[≥3 clinic visits(OR=7.064,95％CI:1.677-29.754)],mixed infection(OR=3.812,95％CI:1.185-12.260),severe disease(OR=3.697,95％CI:1.081-12.646)]were risk factors for diagnosis delay in children.Molecular biological assay(OR=4.642,95％CI:1.318-16.345)was a protective factor.Conclusions The clinical symptoms of tuberculosis in children are atypical.Delayed diagnosis of tuberculosis is common.Multiple clinic visits,mixed infection,and severe disease are the risk factors for diagnosis delay.Tuberculosis should be taken into account for the children with chronic fever,cough and growth retardation who have failed to respond to adequate therapy with third-generation cephalosporin and carbapenems.Molecular biological assay is helpful for early diagnosis of tuberculosis in children with negative sputum smear.

Objective To summarize the clinical characteristics of delayed diagnosis of tuberculosis in children,analyze the risk factors of delayed diagnosis,and support early diagnosis of tuberculosis in children.Methods This is a retrospective analysis based on the clinical data of tuberculosis patients admitted to the Children's Hospital Affiliated to Zhengzhou University from January 2015 to February 2023.The clinical characteristics of children were analyzed in terms of age group.According to the definition of diagnosis delay,the patients were assigned to delayed group and non-delayed group.Univariate analysis and multivariate logistic regression were used to analyze the risk factors for diagnosis delay.Results A total of 82 children with tuberculosis were included(46 cases in delayed diagnosis group and 36 cases in non-delayed diagnosis group).The rate of diagnosis delay was 56.1％.The incidence of acute miliary pulmonary tuberculosis and tuberculous meningitis was significantly higher in children ≤5 years old than that in children＞5 years old(P＜0.05).Diagnosis delay was associated with significantly higher prevalence of chronic fever,cough＞2 weeks,growth retardation and significantly longer duration of empirical antibiotic use compared to the children without diagnosis delay(P＜0.05).Univariate analysis showed that patient origin,contact history,mixed infection,tuberculosis type,molecular biological assay and severe disease were related to the delay of TB diagnosis(P＜0.05).Multivariate logistic regression analysis showed that patient origin[≥3 clinic visits(OR=7.064,95％CI:1.677-29.754)],mixed infection(OR=3.812,95％CI:1.185-12.260),severe disease(OR=3.697,95％CI:1.081-12.646)]were risk factors for diagnosis delay in children.Molecular biological assay(OR=4.642,95％CI:1.318-16.345)was a protective factor.Conclusions The clinical symptoms of tuberculosis in children are atypical.Delayed diagnosis of tuberculosis is common.Multiple clinic visits,mixed infection,and severe disease are the risk factors for diagnosis delay.Tuberculosis should be taken into account for the children with chronic fever,cough and growth retardation who have failed to respond to adequate therapy with third-generation cephalosporin and carbapenems.Molecular biological assay is helpful for early diagnosis of tuberculosis in children with negative sputum smear.

Objective To summarize the clinical characteristics of delayed diagnosis of tuberculosis in children,analyze the risk factors of delayed diagnosis,and support early diagnosis of tuberculosis in children.Methods This is a retrospective analysis based on the clinical data of tuberculosis patients admitted to the Children's Hospital Affiliated to Zhengzhou University from January 2015 to February 2023.The clinical characteristics of children were analyzed in terms of age group.According to the definition of diagnosis delay,the patients were assigned to delayed group and non-delayed group.Univariate analysis and multivariate logistic regression were used to analyze the risk factors for diagnosis delay.Results A total of 82 children with tuberculosis were included(46 cases in delayed diagnosis group and 36 cases in non-delayed diagnosis group).The rate of diagnosis delay was 56.1％.The incidence of acute miliary pulmonary tuberculosis and tuberculous meningitis was significantly higher in children ≤5 years old than that in children＞5 years old(P＜0.05).Diagnosis delay was associated with significantly higher prevalence of chronic fever,cough＞2 weeks,growth retardation and significantly longer duration of empirical antibiotic use compared to the children without diagnosis delay(P＜0.05).Univariate analysis showed that patient origin,contact history,mixed infection,tuberculosis type,molecular biological assay and severe disease were related to the delay of TB diagnosis(P＜0.05).Multivariate logistic regression analysis showed that patient origin[≥3 clinic visits(OR=7.064,95％CI:1.677-29.754)],mixed infection(OR=3.812,95％CI:1.185-12.260),severe disease(OR=3.697,95％CI:1.081-12.646)]were risk factors for diagnosis delay in children.Molecular biological assay(OR=4.642,95％CI:1.318-16.345)was a protective factor.Conclusions The clinical symptoms of tuberculosis in children are atypical.Delayed diagnosis of tuberculosis is common.Multiple clinic visits,mixed infection,and severe disease are the risk factors for diagnosis delay.Tuberculosis should be taken into account for the children with chronic fever,cough and growth retardation who have failed to respond to adequate therapy with third-generation cephalosporin and carbapenems.Molecular biological assay is helpful for early diagnosis of tuberculosis in children with negative sputum smear.

Objective To summarize the clinical characteristics of delayed diagnosis of tuberculosis in children,analyze the risk factors of delayed diagnosis,and support early diagnosis of tuberculosis in children.Methods This is a retrospective analysis based on the clinical data of tuberculosis patients admitted to the Children's Hospital Affiliated to Zhengzhou University from January 2015 to February 2023.The clinical characteristics of children were analyzed in terms of age group.According to the definition of diagnosis delay,the patients were assigned to delayed group and non-delayed group.Univariate analysis and multivariate logistic regression were used to analyze the risk factors for diagnosis delay.Results A total of 82 children with tuberculosis were included(46 cases in delayed diagnosis group and 36 cases in non-delayed diagnosis group).The rate of diagnosis delay was 56.1％.The incidence of acute miliary pulmonary tuberculosis and tuberculous meningitis was significantly higher in children ≤5 years old than that in children＞5 years old(P＜0.05).Diagnosis delay was associated with significantly higher prevalence of chronic fever,cough＞2 weeks,growth retardation and significantly longer duration of empirical antibiotic use compared to the children without diagnosis delay(P＜0.05).Univariate analysis showed that patient origin,contact history,mixed infection,tuberculosis type,molecular biological assay and severe disease were related to the delay of TB diagnosis(P＜0.05).Multivariate logistic regression analysis showed that patient origin[≥3 clinic visits(OR=7.064,95％CI:1.677-29.754)],mixed infection(OR=3.812,95％CI:1.185-12.260),severe disease(OR=3.697,95％CI:1.081-12.646)]were risk factors for diagnosis delay in children.Molecular biological assay(OR=4.642,95％CI:1.318-16.345)was a protective factor.Conclusions The clinical symptoms of tuberculosis in children are atypical.Delayed diagnosis of tuberculosis is common.Multiple clinic visits,mixed infection,and severe disease are the risk factors for diagnosis delay.Tuberculosis should be taken into account for the children with chronic fever,cough and growth retardation who have failed to respond to adequate therapy with third-generation cephalosporin and carbapenems.Molecular biological assay is helpful for early diagnosis of tuberculosis in children with negative sputum smear.

Objective To summarize the clinical characteristics of delayed diagnosis of tuberculosis in children,analyze the risk factors of delayed diagnosis,and support early diagnosis of tuberculosis in children.Methods This is a retrospective analysis based on the clinical data of tuberculosis patients admitted to the Children's Hospital Affiliated to Zhengzhou University from January 2015 to February 2023.The clinical characteristics of children were analyzed in terms of age group.According to the definition of diagnosis delay,the patients were assigned to delayed group and non-delayed group.Univariate analysis and multivariate logistic regression were used to analyze the risk factors for diagnosis delay.Results A total of 82 children with tuberculosis were included(46 cases in delayed diagnosis group and 36 cases in non-delayed diagnosis group).The rate of diagnosis delay was 56.1％.The incidence of acute miliary pulmonary tuberculosis and tuberculous meningitis was significantly higher in children ≤5 years old than that in children＞5 years old(P＜0.05).Diagnosis delay was associated with significantly higher prevalence of chronic fever,cough＞2 weeks,growth retardation and significantly longer duration of empirical antibiotic use compared to the children without diagnosis delay(P＜0.05).Univariate analysis showed that patient origin,contact history,mixed infection,tuberculosis type,molecular biological assay and severe disease were related to the delay of TB diagnosis(P＜0.05).Multivariate logistic regression analysis showed that patient origin[≥3 clinic visits(OR=7.064,95％CI:1.677-29.754)],mixed infection(OR=3.812,95％CI:1.185-12.260),severe disease(OR=3.697,95％CI:1.081-12.646)]were risk factors for diagnosis delay in children.Molecular biological assay(OR=4.642,95％CI:1.318-16.345)was a protective factor.Conclusions The clinical symptoms of tuberculosis in children are atypical.Delayed diagnosis of tuberculosis is common.Multiple clinic visits,mixed infection,and severe disease are the risk factors for diagnosis delay.Tuberculosis should be taken into account for the children with chronic fever,cough and growth retardation who have failed to respond to adequate therapy with third-generation cephalosporin and carbapenems.Molecular biological assay is helpful for early diagnosis of tuberculosis in children with negative sputum smear.

Objective To summarize the clinical characteristics of delayed diagnosis of tuberculosis in children,analyze the risk factors of delayed diagnosis,and support early diagnosis of tuberculosis in children.Methods This is a retrospective analysis based on the clinical data of tuberculosis patients admitted to the Children's Hospital Affiliated to Zhengzhou University from January 2015 to February 2023.The clinical characteristics of children were analyzed in terms of age group.According to the definition of diagnosis delay,the patients were assigned to delayed group and non-delayed group.Univariate analysis and multivariate logistic regression were used to analyze the risk factors for diagnosis delay.Results A total of 82 children with tuberculosis were included(46 cases in delayed diagnosis group and 36 cases in non-delayed diagnosis group).The rate of diagnosis delay was 56.1％.The incidence of acute miliary pulmonary tuberculosis and tuberculous meningitis was significantly higher in children ≤5 years old than that in children＞5 years old(P＜0.05).Diagnosis delay was associated with significantly higher prevalence of chronic fever,cough＞2 weeks,growth retardation and significantly longer duration of empirical antibiotic use compared to the children without diagnosis delay(P＜0.05).Univariate analysis showed that patient origin,contact history,mixed infection,tuberculosis type,molecular biological assay and severe disease were related to the delay of TB diagnosis(P＜0.05).Multivariate logistic regression analysis showed that patient origin[≥3 clinic visits(OR=7.064,95％CI:1.677-29.754)],mixed infection(OR=3.812,95％CI:1.185-12.260),severe disease(OR=3.697,95％CI:1.081-12.646)]were risk factors for diagnosis delay in children.Molecular biological assay(OR=4.642,95％CI:1.318-16.345)was a protective factor.Conclusions The clinical symptoms of tuberculosis in children are atypical.Delayed diagnosis of tuberculosis is common.Multiple clinic visits,mixed infection,and severe disease are the risk factors for diagnosis delay.Tuberculosis should be taken into account for the children with chronic fever,cough and growth retardation who have failed to respond to adequate therapy with third-generation cephalosporin and carbapenems.Molecular biological assay is helpful for early diagnosis of tuberculosis in children with negative sputum smear.