The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 is a mitochondrial phosphatase involved in NLRP3 inflammasome activation in macrophages. However, the role of PGAM5 in ulcerative colitis and the mechanisms underlying PGAM5 regulating NLRP3 activity remain unknown. Here, we show that PGAM5 deficiency ameliorates dextran sodium sulfate (DSS)-induced colitis in mice via suppressing NLRP3 inflammasome activation. By combining APEX2-based proximity labeling focused on PGAM5 with quantitative proteomics, we identify NEK7 as the new binding partner of PGAM5 to promote NLRP3 inflammasome assembly and activation in a PGAM5 phosphatase activity-independent manner upon inflammasome induction. Interfering with PGAM5-NEK7 interaction by punicalagin inhibits the activation of the NLRP3 inflammasome in macrophages and ameliorates DSS-induced colitis in mice. Altogether, our data demonstrate the PGAM5-NEK7 interaction in macrophages for NLRP3 inflammasome activation and further provide a promising therapeutic strategy for ulcerative colitis by blocking the PGAM5-NEK7 interaction.

Objective To investigate the relationship between type 2 diabetes mellitus(T2DM)and cognitive decline.Methods Data were obtained from the cognitive impairment cohort of middle-aged and elderly population in rural areas of Xi'an City.The cohort consisted of residents aged 40 years and older in two villages of Huyi District,Xi'an.The baseline survey was completed between October 2014 and March 2015,with two follow-up visits in 2016 and 2018.The present study was conducted on cognitively normal people at baseline.Individual characteristics,lifestyle,and medical history were collected;physical and biochemical examinations were completed.According to medical history of T2DM and fasting blood glucose,the study population was divided into non-T2DM group,pre-existing T2DM group,and new-onset T2DM group.The Mini-Mental State Examination(MMSE)was used to assess global cognitive function.Participants with a drop of≥2 points in MMSE score from baseline after 4 years were defined as having cognitive decline.Chi-square test and multivariate Logistic regression analysis were employed to analyze the effect of T2DM status on the risk of cognitive decline.Results A total of 1 350 subjects completed the follow-up.In the follow-up population,1 096(81.2％)were free of T2DM,158(11.7％)already had T2DM at baseline,and 96(7.1％)developed new-onset T2DM during the follow-up.Cognitive decline was observed in 230 individuals after 4 years,representing 17.0％of the study population.The new-onset T2DM group had the highest 4-year incidence of cognitive decline(non-T2DM group vs.pre-existing T2DM group vs.new-onset T2DM group:15.7％vs.20.9％vs.26.0％,P=0.014),and the incidence of cognitive decline in the newly-onset T2DM group was significantly higher than that in the non-T2DM group(P=0.009).Multivariate Logistic regression analysis showed that the new-onset T2DM group had an increased risk of cognitive decline compared with the non-T2DM group within 4 years(OR=1.726,95％CI:1.029-2.896,P=0.039).However,no significant difference in 4-year risk of cognitive decline in the pre-existing T2DM group was observed(OR=1.402,95％CI:0.890-2.210,P=0.145).Conclusion Through the 4-year follow-up study of cognitively normal adults aged 40 and above in rural Xi'an,it was found that new-onset T2DM patients face a significantly elevated risk of cognitive decline,suggesting that cognitive decline may occur in the early stage of T2DM.

Objective To establish a highly sensitive and specific method for detecting human DNA based on real time quantitative PCR(qPCR)technique for the rapid detection of potential DNA con-tamination sources in DNA laboratories.Methods Primers and probes were designed with Primer Ex-pressTM software using the reference sequence of human 18S rRNA gene as a template,and the opti-mal prime-probe combination was screened by matrix method.The PCR products of the target se-quence of human 18S rRNA gene were used to construct the plasmid,and a plasmid standard was used to draw the standard curve of the qPCR system.According to the Minimum Information for Pub-lication of Quantitative Real-time PCR Experiments(MIQE)guidelines,the specificity,sensitivity,re-peatability and application effect of the qPCR system were evaluated.Results The sensitivity of the qPCR system established in this study was 5.3×10-5 ng/μL,which showed good specificity for human DNA samples.The correlation coefficient of the qPCR system was-0.999,and amplification efficiency was 100％.Both the intra-batch and inter-batch variation coefficients were less than 2％.Conclusion The established human DNA detection method based on qPCR technique has good specificity,high sen-sitivity,and robust stability.It can be used for rapid detection of DNA contamination and daily moni-toring of the accumulated human DNA in the laboratory environment.

Objective To summarize the characteristics of the constitution of orthopedic diseases among soldiers in a sea area,so as to provide the reference for the rational allocation of medical resources,the prevention and treatment of orthopedic diseases,and the improvement of naval medical support.Methods Medical records on injuries of the outpatient and emergency departments in a hospital ship from February 2021 to April 2022 were retrospectively analyzed.The number of varying orthopedic diseases was counted,and descriptive statistical analysis was conducted.Results A total of 200 cases were included in the statistical analysis.The top five diseases were chronic low back pain,knee pain,tibial contusion,wrist joint injury,and shoulder joint injury,and they accounted for 82%of the total orthopedic diseases.Conclusion The medical team stationed on hospital ships should be guided by actual medical needs of officers and soldiers on island,enhance the diagnosis and treatment of common orthopedic diseases,formulate scientific and reasonable prevention and treatment strategies.The allocation of medical materials and personnel should be in line with the spectrum of orthopedic diseases as far as possible to reduce non-combat casualty and strengthen the combat effectiveness of the army.

Ischemic stroke and hemorrhagic stroke have different pathogenic mechanisms,but share similarities in metabolic dysregulation,inflammatory responses and oxidative stress.This paper summarized 28 metabolic markers shared between ischemic stroke and hemorrhagic stroke with consistent trends through literature review.It also provided an overview of their involvement in abnormal energy metabolism,inflammatory responses,blood-brain barrier disruption,and neural damage in relation to stroke.The aim is to provide a scientific basis for future prognosis,curative efficacy evaluation and future homotherapy of ischemic stroke and hemorrhagic stroke,and provide insights for the development of new therapies and new drugs.

Ischemic stroke and hemorrhagic stroke have different pathogenic mechanisms,but share similarities in metabolic dysregulation,inflammatory responses and oxidative stress.This paper summarized 28 metabolic markers shared between ischemic stroke and hemorrhagic stroke with consistent trends through literature review.It also provided an overview of their involvement in abnormal energy metabolism,inflammatory responses,blood-brain barrier disruption,and neural damage in relation to stroke.The aim is to provide a scientific basis for future prognosis,curative efficacy evaluation and future homotherapy of ischemic stroke and hemorrhagic stroke,and provide insights for the development of new therapies and new drugs.

Tic disorder is a chronic neuropsychiatric disorder with complex etiology and diverse phenotypes,and its incidence has been increasing significantly in recent years.Most scholars believe that abnormalities in the cortico-striatal-thalamo-cortical circuit and its interconnected brain regions are closely related to the development of tic disorder.Chinese materia medica intervention in tic disorders is characterized by multi-targets,multi-mechanisms and holistic nature,and has a good prospect for research application.This article summarized the experimental studies of TCM compound intervention in tic disorder in recent years,which have shown that TCM compounds could reduce the damage of nerve cells through the regulation of neurotransmitters,inflammatory response,immune function and the"colony-gut-brain axis"to improve and prevent tic disorder,which could provide a reference for the research and development of new medicines for tic disorder and for the clinical research.

Tic disorder is a chronic neuropsychiatric disorder with complex etiology and diverse phenotypes,and its incidence has been increasing significantly in recent years.Most scholars believe that abnormalities in the cortico-striatal-thalamo-cortical circuit and its interconnected brain regions are closely related to the development of tic disorder.Chinese materia medica intervention in tic disorders is characterized by multi-targets,multi-mechanisms and holistic nature,and has a good prospect for research application.This article summarized the experimental studies of TCM compound intervention in tic disorder in recent years,which have shown that TCM compounds could reduce the damage of nerve cells through the regulation of neurotransmitters,inflammatory response,immune function and the"colony-gut-brain axis"to improve and prevent tic disorder,which could provide a reference for the research and development of new medicines for tic disorder and for the clinical research.

Objective To investigate the relationship between type 2 diabetes mellitus(T2DM)and cognitive decline.Methods Data were obtained from the cognitive impairment cohort of middle-aged and elderly population in rural areas of Xi'an City.The cohort consisted of residents aged 40 years and older in two villages of Huyi District,Xi'an.The baseline survey was completed between October 2014 and March 2015,with two follow-up visits in 2016 and 2018.The present study was conducted on cognitively normal people at baseline.Individual characteristics,lifestyle,and medical history were collected;physical and biochemical examinations were completed.According to medical history of T2DM and fasting blood glucose,the study population was divided into non-T2DM group,pre-existing T2DM group,and new-onset T2DM group.The Mini-Mental State Examination(MMSE)was used to assess global cognitive function.Participants with a drop of≥2 points in MMSE score from baseline after 4 years were defined as having cognitive decline.Chi-square test and multivariate Logistic regression analysis were employed to analyze the effect of T2DM status on the risk of cognitive decline.Results A total of 1 350 subjects completed the follow-up.In the follow-up population,1 096(81.2％)were free of T2DM,158(11.7％)already had T2DM at baseline,and 96(7.1％)developed new-onset T2DM during the follow-up.Cognitive decline was observed in 230 individuals after 4 years,representing 17.0％of the study population.The new-onset T2DM group had the highest 4-year incidence of cognitive decline(non-T2DM group vs.pre-existing T2DM group vs.new-onset T2DM group:15.7％vs.20.9％vs.26.0％,P=0.014),and the incidence of cognitive decline in the newly-onset T2DM group was significantly higher than that in the non-T2DM group(P=0.009).Multivariate Logistic regression analysis showed that the new-onset T2DM group had an increased risk of cognitive decline compared with the non-T2DM group within 4 years(OR=1.726,95％CI:1.029-2.896,P=0.039).However,no significant difference in 4-year risk of cognitive decline in the pre-existing T2DM group was observed(OR=1.402,95％CI:0.890-2.210,P=0.145).Conclusion Through the 4-year follow-up study of cognitively normal adults aged 40 and above in rural Xi'an,it was found that new-onset T2DM patients face a significantly elevated risk of cognitive decline,suggesting that cognitive decline may occur in the early stage of T2DM.