In recent decades, the prevalence of hyperuricemia and gout has increased dramatically due to lifestyle changes. The drugs currently recommended for hyperuricemia are associated with adverse reactions that limit their clinical use. In this study, we report that berberine (BBR) is an effective drug candidate for the treatment of hyperuricemia, with its mechanism potentially involving the modulation of gut microbiota and its metabolite, succinic acid. BBR has demonstrated good therapeutic effects in both acute and chronic animal models of hyperuricemia. In a clinical trial, oral administration of BBR for 6 months reduced blood uric acid levels in 22 participants by modulating the gut microbiota, which led to an increase in the abundance of Bacteroides and a decrease in Clostridium sensu stricto_1. Furthermore, Bacteroides fragilis was transplanted into ICR mice, and the results showed that Bacteroides fragilis exerted a therapeutic effect on uric acid similar to that of BBR. Notably, succinic acid, a metabolite of Bacteroides, significantly reduced uric acid levels. Subsequent cell and animal experiments revealed that the intestinal metabolite, succinic acid, regulated the upstream uric acid synthesis pathway in the liver by inhibiting adenosine monophosphate deaminase 2 (AMPD2), an enzyme responsible for converting adenosine monophosphate (AMP) to inosine monophosphate (IMP). This inhibition resulted in a decrease in IMP levels and an increase in phosphate levels. The reduction in IMP led to a decreased downstream production of hypoxanthine, xanthine, and uric acid. BBR also demonstrated excellent renoprotective effects, improving nephropathy associated with hyperuricemia. In summary, BBR has the potential to be an effective treatment for hyperuricemia through the gut-liver axis.

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 evaluate the application effect of management mode based on constraint theory for medical equipment in equipment management of vascular surgery. Methods:Based on five-step method of constraint theory,an operation evaluation system was formulated. An information management mode of medical equipment was constructed to manage quality of medical equipment in department of vascular surgery. A total of 60 sets used medical equipment in the Department of Vascular Surgery at The Second Affiliated Hospital of Xi'an Jiaotong University from 2021 to 2022 were selected. The conventional management mode was adopted to manage these equipment between January to December 2021,while equipment was managed by using medical equipment management mode based on constraint theory (constraint theory management) of the department of vascular surgery from January to December 2022. The quality scores of operation and maintenance of equipment,average incidence rates of risk,configuration effectiveness,and timeliness of equipment management were compared between the two management modes. Results:After constraint theory management was implemented,the average scores of operation and maintenance of equipment,which included success starting-up,operation,routine maintenance and fault repair,were respectively (90.69±8.65),(89.65±4.65),(88.65±5.63),and (90.58±6.01),all of which were higher than those of conventional management mode. The differences of them between two modes were statistically significant (t=13.482,17.867,14.552,14.449,P<0.05). The average incidence rates of the risks of testing equipment,treatment,monitoring equipment and auxiliary equipment of adopting constraint theory mode management were (0.89±0.22)％,(0.84±0.23)％,(0.74±0.32)％ and (0.75±0.32％),all which were lower than those of the conventional management mode,with statistically significant differences (t=9.162,17.745,19.469,15.019,P<0.05). The average utilization rate of equipment and the average amplification of cost benefit of equipment were respectively (88.69±5.54)％ and (50.36±2.69)％ after constraint theory mode was adopted,which were significantly higher than those of conventional management mode,and the average floating rate of using equipment of constraint theory mode was (1.23±0.97)％,which was lower than that of conventional management model,the differences of them between two modes were statistically significant (t=14.174,21.564,11.811,P<0.05). The average times of emergency management for risk events included the safety of power consumption of equipment,safety of diagnosis and treatment,biological safety and radiation safety were respectively (2.36±0.64)h,(3.26±0.78)h,(4.23±1.24)h and (2.26±1.23)h after the constraint theory mode was adopted,all of which were significantly less than those of conventional management mode,and the differences of them between two modes were statistically significant (t=16.704,13.421,9.029,13.971,P<0.05). Conclusion:The application of the management mode based on the constraint theory of medical equipment in department of vascular surgery can improve the quality of operation and maintenance of equipment for safety,and shorten the emergency response time of equipment,and reduce the incidence of equipment risk,and strengthen the effect of configuration for equipment.

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.

A 67-year-old female patient with erythrodermic psoriasis showed no significant improvement in rash after 2 weeks of treatments with acitretin, ebastine, etc., with the psoriasis area and severity index (PASI) score of 72 points (the highest value). Secukinumab 300 mg once a week was given by subcutaneous injection, which was changed to 300 mg once a month after 5 weeks of medication. After 5 weeks of treatment(medication 5 times), the patient′s PASI improvement rate was 75%, but the patient developed alopecia areata and her eyebrows fall off. After 6 months of treatment, the PASI improvement rate was 100%, but the patient developed alopecia totalis and her eyebrows completely disappeared. During the 9-month follow-up, the patient did not stop taking medication or received hair loss treatment. No psoriasis rash recurred and her hair loss was not improved.

Objective:To evaluate the application effect of management mode based on constraint theory for medical equipment in equipment management of vascular surgery. Methods:Based on five-step method of constraint theory,an operation evaluation system was formulated. An information management mode of medical equipment was constructed to manage quality of medical equipment in department of vascular surgery. A total of 60 sets used medical equipment in the Department of Vascular Surgery at The Second Affiliated Hospital of Xi'an Jiaotong University from 2021 to 2022 were selected. The conventional management mode was adopted to manage these equipment between January to December 2021,while equipment was managed by using medical equipment management mode based on constraint theory (constraint theory management) of the department of vascular surgery from January to December 2022. The quality scores of operation and maintenance of equipment,average incidence rates of risk,configuration effectiveness,and timeliness of equipment management were compared between the two management modes. Results:After constraint theory management was implemented,the average scores of operation and maintenance of equipment,which included success starting-up,operation,routine maintenance and fault repair,were respectively (90.69±8.65),(89.65±4.65),(88.65±5.63),and (90.58±6.01),all of which were higher than those of conventional management mode. The differences of them between two modes were statistically significant (t=13.482,17.867,14.552,14.449,P<0.05). The average incidence rates of the risks of testing equipment,treatment,monitoring equipment and auxiliary equipment of adopting constraint theory mode management were (0.89±0.22)％,(0.84±0.23)％,(0.74±0.32)％ and (0.75±0.32％),all which were lower than those of the conventional management mode,with statistically significant differences (t=9.162,17.745,19.469,15.019,P<0.05). The average utilization rate of equipment and the average amplification of cost benefit of equipment were respectively (88.69±5.54)％ and (50.36±2.69)％ after constraint theory mode was adopted,which were significantly higher than those of conventional management mode,and the average floating rate of using equipment of constraint theory mode was (1.23±0.97)％,which was lower than that of conventional management model,the differences of them between two modes were statistically significant (t=14.174,21.564,11.811,P<0.05). The average times of emergency management for risk events included the safety of power consumption of equipment,safety of diagnosis and treatment,biological safety and radiation safety were respectively (2.36±0.64)h,(3.26±0.78)h,(4.23±1.24)h and (2.26±1.23)h after the constraint theory mode was adopted,all of which were significantly less than those of conventional management mode,and the differences of them between two modes were statistically significant (t=16.704,13.421,9.029,13.971,P<0.05). Conclusion:The application of the management mode based on the constraint theory of medical equipment in department of vascular surgery can improve the quality of operation and maintenance of equipment for safety,and shorten the emergency response time of equipment,and reduce the incidence of equipment risk,and strengthen the effect of configuration for equipment.

A 67-year-old female patient with erythrodermic psoriasis showed no significant improvement in rash after 2 weeks of treatments with acitretin, ebastine, etc., with the psoriasis area and severity index (PASI) score of 72 points (the highest value). Secukinumab 300 mg once a week was given by subcutaneous injection, which was changed to 300 mg once a month after 5 weeks of medication. After 5 weeks of treatment(medication 5 times), the patient′s PASI improvement rate was 75%, but the patient developed alopecia areata and her eyebrows fall off. After 6 months of treatment, the PASI improvement rate was 100%, but the patient developed alopecia totalis and her eyebrows completely disappeared. During the 9-month follow-up, the patient did not stop taking medication or received hair loss treatment. No psoriasis rash recurred and her hair loss was not improved.

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.