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 study the therapeutic effect of Hongqi Shenmai Drink on heart failure(HF)after acute myocardial in-farction(AMI)with qi-yin deficiency and blood stasis,and its regulatory effect on serum secretory phosphoprotein 1(SPP1)in AMI-HF patients.METHODS Seventy-six patients with AMI-HF of qi-yin deficiency and blood stasis type were enrolled in this study from three centers:Affiliated Hospital of Integrated Traditional and Western Medicine,Nanjing University of Chinese Medicine;Hangzhou Xiaoshan Hospital of Traditional Chinese Medicine;and Changzhou Hospital of Traditional Chinese Medicine.They were randomly di-vided into a traditional Chinese medicine(TCM)group and a control group,with 38 patients in each group.During the treatment period,4 patients in the TCM group and 3 patients in the control group dropped out.The control group received conventional Guideline-directed medical therapy(GDMT),while the TCM group received GDMT plus Hongqi Shenmai Drink.The treatment course for both groups was 12 weeks.The TCM syndrome scores of the two groups of patients were compared before and after treatment,and the clini-cal efficacy and readmission rate were assessed.Echocardiography was used to assess cardiac structure and function.ELISA was used to detect changes in serum SPP1,N-terminal pro-brain natriuretic peptide(NT-proBNP),interleukin-1β(IL-1β),type Ⅰ collagen α1(COL1α1),and matrix metalloproteinase 9(MMP9)levels.The 6-minute walk test(6MWT)was used to assess exercise tolerance,and the Minnesota living with heart failure questionnaire(MLHFQ)was used to assess patients'quality of life.Adverse reactions were monitored in both groups during treatment.RESULTS After treatment,the TCM syndrome scores of both groups decreased signifi-cantly(P<0.01),with the TCM group showing a significantly lower score than the control group(P<0.01).The total effective rate of TCM clinical efficacy in the TCM group was superior to that in the control group(P<0.05),and the readmission rate in the TCM group was significantly lower than that in the control group(P<0.01).Left ventricular end diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),left ventricular ejection fraction(LVEF),6MWT,and MLHFQ scores improved in both groups(P<0.01),with the TCM group showing superior improvement compared to the control group(P<0.05,P<0.01).Serum levels of NT-proBNP,IL-1β,COL1α1,and MMP9 decreased in both groups(P<0.05,P<0.01).Serum SPP1 levels were significantly decreased in the TCM group(P<0.01),and serum levels of NT-proBNP,IL-1β,COL1α1,and MMP9 in the TCM group were significantly lower than those in the con-trol group(P<0.01).The change in SPP1(ΔSPP1)showed a negative correlation with the change in the cardiac function ΔLVEF(r=-0.42,P<0.01),and a positive correlation with the myocardial fibrosis marker ΔCOL1α1(r=0.58,P<0.01)and the matrix degradation marker ΔMMP9(r=0.51,P<0.01).There was no significant difference in adverse reaction rates between the two groups during treat-ment(P>0.05).CONCLUSION Hongqi Shenmai Drink combined with GDMT can effectively improve clinical symptoms and cardiac function in patients with AMI-HF of qi-yin deficiency and blood stasis type,with good safety.Its mechanism may be related to the in-hibition of SPP1-mediated inflammation-fibrosis pathway and the downregulation of IL-1β,COL1α1,and MMP9 expression.

To investigate the distribution and biological characteristics of Trueperella pyogenes in caprine mastitis,67 milk samples from were collected from goats with mastitis in 9 dairy goat farms in the Guanzhong area of Shaanxi Province.A total of 21 strains of T.pyogenes were isolated through bacterial separation and culture.PCR amplification was conducted for 8 virulence genes of the 21 isolated strains,and the susceptibility of the strains to 10 antimicrobial drugs was tested u-sing the micro broth dilution method.Nine selected strains were subjected to genomic sequencing using Illumina Nova Seq 6000 next-generation sequencing technology,and their pathogenicity was verified by inoculating mice through the teat canal.The results of virulence gene detection showed that the positive rates of plo,cbpA,nanH,nanP,fimA,fimC-,and fimE genes among the 21 iso-lated strains were 100.0％,38.1％,52.6％,31.6％,61.9％,57.1％,and 52.4％,respectively.In con-trast,the fimG gene was not detected,which was consistent with the results of genomic compari-son by next-generation sequencing.The drug susceptibility test results showed that the susceptibil-ity rates of the isolated strains to clindamycin(CLI),ceftiofur(CEF),and vancomycin(VAN)were 100.0％,while the resistance rates to penicillin(PEN),erythromycin(ERY),sulfamethox-azole-trimethoprim(SXT),florfenicol(FFC),tetracycline(TE),gentamicin(GEN),and enroflox-acin(ENR)were 76.2％,52.1％,52.4％,52.4％,47.6％,42.9％,and 33.3％,respectively.The pro-portion of strains resistant to at least three antimicrobial drugs was 71.4％(15/21).ResFinder a-nalysis of the resistant genes identified 8 types of resistance genes in the genomes of the 9 strains,including ant(2")-Ia and ant(3")-Ia mediating aminoglycoside resistance,cmlA1 and cmx media-ting chloramphenicol resistance,erm(X)and lnu(A)mediating macrolide resistance,sul1 media-ting sulfonamide resistance,and tet(W)mediating tetracycline resistance.Except for tet(W),cm-lA,and erm(X),the other resistance genes were detected for the first time in T.pyogenes in Chi-na.In animal pathogenicity tests,mice inoculated with the isolated strains showed signs of mastitis such as redness,congestion,and inflammatory cell infiltration in the glandular tissue within 24 h,indicating that the isolated strains have pathogenicity to mouse mammary tissue.This study pro-vides preliminary insights into the biological characteristics and pathogenicity of T.pyogenes from caprine mastitis,enriching the data on its drug resistance and genomics,and offering reference and guidance for the prevention and treatment of T.pyogenes infections in large-scale dairy goat farm-ing.

The clinical diagnosis and treatment of urinary tract infection has long faced the challenges of insufficient standardization of diagnosis and treatment pathways,irrational use of antimicrobial drugs and high recurrence rate.How to optimize the hierarchical diagnosis and treatment pathway of urinary tract infection,standardize the use of antimicrobial drugs,and reduce the recurrence rate have always been the focus of clinical attention.There is significant heterogeneity in the existing diagnostic criteria for urinary tract infection,which seriously affects the comparability and evidence integration of clinical and research studies.In order to solve the above problems,a consensus on global multidisciplinary diagnostic criteria for urinary tract infection has been formed by international multidisciplinary experts after three rounds of Delphi method.Breaking through the traditional classification framework,the consensus innovatively established a four-dimensional quantitative scoring system including local symptoms and signs,systemic inflammatory response,quantitative analysis of pyuria and urine culture results,and established a hierarchical standard for stepwise urinary tract diagnosis according to the scoring threshold.Based on the key citations related to the consensus,this paper interprets in detail the basis for the selection of core indicators and the establishment of thresholds for the diagnosis of urinary tract infection in the consensus,and focuses on the key issues and implementation paths of the consensus in localization practice.This consensus provides a unified standard for standardizing the clinical diagnosis and treatment of urinary tract infection,improving the homogeneity of clinical research through standardized diagnostic processes,and promoting the standardization of UTI drug research and development and the rational use of antibiotics and precision.

OBJECTIVE To study the therapeutic effect of Hongqi Shenmai Drink on heart failure(HF)after acute myocardial in-farction(AMI)with qi-yin deficiency and blood stasis,and its regulatory effect on serum secretory phosphoprotein 1(SPP1)in AMI-HF patients.METHODS Seventy-six patients with AMI-HF of qi-yin deficiency and blood stasis type were enrolled in this study from three centers:Affiliated Hospital of Integrated Traditional and Western Medicine,Nanjing University of Chinese Medicine;Hangzhou Xiaoshan Hospital of Traditional Chinese Medicine;and Changzhou Hospital of Traditional Chinese Medicine.They were randomly di-vided into a traditional Chinese medicine(TCM)group and a control group,with 38 patients in each group.During the treatment period,4 patients in the TCM group and 3 patients in the control group dropped out.The control group received conventional Guideline-directed medical therapy(GDMT),while the TCM group received GDMT plus Hongqi Shenmai Drink.The treatment course for both groups was 12 weeks.The TCM syndrome scores of the two groups of patients were compared before and after treatment,and the clini-cal efficacy and readmission rate were assessed.Echocardiography was used to assess cardiac structure and function.ELISA was used to detect changes in serum SPP1,N-terminal pro-brain natriuretic peptide(NT-proBNP),interleukin-1β(IL-1β),type Ⅰ collagen α1(COL1α1),and matrix metalloproteinase 9(MMP9)levels.The 6-minute walk test(6MWT)was used to assess exercise tolerance,and the Minnesota living with heart failure questionnaire(MLHFQ)was used to assess patients'quality of life.Adverse reactions were monitored in both groups during treatment.RESULTS After treatment,the TCM syndrome scores of both groups decreased signifi-cantly(P<0.01),with the TCM group showing a significantly lower score than the control group(P<0.01).The total effective rate of TCM clinical efficacy in the TCM group was superior to that in the control group(P<0.05),and the readmission rate in the TCM group was significantly lower than that in the control group(P<0.01).Left ventricular end diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),left ventricular ejection fraction(LVEF),6MWT,and MLHFQ scores improved in both groups(P<0.01),with the TCM group showing superior improvement compared to the control group(P<0.05,P<0.01).Serum levels of NT-proBNP,IL-1β,COL1α1,and MMP9 decreased in both groups(P<0.05,P<0.01).Serum SPP1 levels were significantly decreased in the TCM group(P<0.01),and serum levels of NT-proBNP,IL-1β,COL1α1,and MMP9 in the TCM group were significantly lower than those in the con-trol group(P<0.01).The change in SPP1(ΔSPP1)showed a negative correlation with the change in the cardiac function ΔLVEF(r=-0.42,P<0.01),and a positive correlation with the myocardial fibrosis marker ΔCOL1α1(r=0.58,P<0.01)and the matrix degradation marker ΔMMP9(r=0.51,P<0.01).There was no significant difference in adverse reaction rates between the two groups during treat-ment(P>0.05).CONCLUSION Hongqi Shenmai Drink combined with GDMT can effectively improve clinical symptoms and cardiac function in patients with AMI-HF of qi-yin deficiency and blood stasis type,with good safety.Its mechanism may be related to the in-hibition of SPP1-mediated inflammation-fibrosis pathway and the downregulation of IL-1β,COL1α1,and MMP9 expression.

The clinical diagnosis and treatment of urinary tract infection has long faced the challenges of insufficient standardization of diagnosis and treatment pathways,irrational use of antimicrobial drugs and high recurrence rate.How to optimize the hierarchical diagnosis and treatment pathway of urinary tract infection,standardize the use of antimicrobial drugs,and reduce the recurrence rate have always been the focus of clinical attention.There is significant heterogeneity in the existing diagnostic criteria for urinary tract infection,which seriously affects the comparability and evidence integration of clinical and research studies.In order to solve the above problems,a consensus on global multidisciplinary diagnostic criteria for urinary tract infection has been formed by international multidisciplinary experts after three rounds of Delphi method.Breaking through the traditional classification framework,the consensus innovatively established a four-dimensional quantitative scoring system including local symptoms and signs,systemic inflammatory response,quantitative analysis of pyuria and urine culture results,and established a hierarchical standard for stepwise urinary tract diagnosis according to the scoring threshold.Based on the key citations related to the consensus,this paper interprets in detail the basis for the selection of core indicators and the establishment of thresholds for the diagnosis of urinary tract infection in the consensus,and focuses on the key issues and implementation paths of the consensus in localization practice.This consensus provides a unified standard for standardizing the clinical diagnosis and treatment of urinary tract infection,improving the homogeneity of clinical research through standardized diagnostic processes,and promoting the standardization of UTI drug research and development and the rational use of antibiotics and precision.

To investigate the distribution and biological characteristics of Trueperella pyogenes in caprine mastitis,67 milk samples from were collected from goats with mastitis in 9 dairy goat farms in the Guanzhong area of Shaanxi Province.A total of 21 strains of T.pyogenes were isolated through bacterial separation and culture.PCR amplification was conducted for 8 virulence genes of the 21 isolated strains,and the susceptibility of the strains to 10 antimicrobial drugs was tested u-sing the micro broth dilution method.Nine selected strains were subjected to genomic sequencing using Illumina Nova Seq 6000 next-generation sequencing technology,and their pathogenicity was verified by inoculating mice through the teat canal.The results of virulence gene detection showed that the positive rates of plo,cbpA,nanH,nanP,fimA,fimC-,and fimE genes among the 21 iso-lated strains were 100.0％,38.1％,52.6％,31.6％,61.9％,57.1％,and 52.4％,respectively.In con-trast,the fimG gene was not detected,which was consistent with the results of genomic compari-son by next-generation sequencing.The drug susceptibility test results showed that the susceptibil-ity rates of the isolated strains to clindamycin(CLI),ceftiofur(CEF),and vancomycin(VAN)were 100.0％,while the resistance rates to penicillin(PEN),erythromycin(ERY),sulfamethox-azole-trimethoprim(SXT),florfenicol(FFC),tetracycline(TE),gentamicin(GEN),and enroflox-acin(ENR)were 76.2％,52.1％,52.4％,52.4％,47.6％,42.9％,and 33.3％,respectively.The pro-portion of strains resistant to at least three antimicrobial drugs was 71.4％(15/21).ResFinder a-nalysis of the resistant genes identified 8 types of resistance genes in the genomes of the 9 strains,including ant(2")-Ia and ant(3")-Ia mediating aminoglycoside resistance,cmlA1 and cmx media-ting chloramphenicol resistance,erm(X)and lnu(A)mediating macrolide resistance,sul1 media-ting sulfonamide resistance,and tet(W)mediating tetracycline resistance.Except for tet(W),cm-lA,and erm(X),the other resistance genes were detected for the first time in T.pyogenes in Chi-na.In animal pathogenicity tests,mice inoculated with the isolated strains showed signs of mastitis such as redness,congestion,and inflammatory cell infiltration in the glandular tissue within 24 h,indicating that the isolated strains have pathogenicity to mouse mammary tissue.This study pro-vides preliminary insights into the biological characteristics and pathogenicity of T.pyogenes from caprine mastitis,enriching the data on its drug resistance and genomics,and offering reference and guidance for the prevention and treatment of T.pyogenes infections in large-scale dairy goat farm-ing.

Arteriovenous malformations(AVMs)are a kind of high-flow vascular malformation.AVMs can be classified in many ways,including histo-embryological classification,hemodynamic classification,etc.At present,the two mainstream classification systems used to guide the embolization treatment of peripheral AVMs are proposed by Cho and Yakes respectively based on the angiographic morphology of the lesions.Interventional embolization is the first-line treatment for AVMs.Among the many embolization agents,absolute ethanol is a permanent liquid embolization agent.Absolute ethanol can directly destroy the vascular endothelial cells to achieve a good curative efficacy,therefore,it has been wildly used in the treatment of peripheral AVMs.Yakes classification combines the angiographic classification with absolute ethanol embolization therapy.During absolute ethanol treatment,close attention should be paid to the occurrence of complications such as elevated pulmonary artery pressure.Although there are challenges remaining in the treatment of AVMs,the rapid development of molecular genetics has made targeted drug adjunctive treatment for AVMs possible.Perhaps,the novel therapeutic mode of combination use of traditional therapy targeted drug may be able to make a breakthrough in the treatment of AVMs.

BACKGROUND:MXene nanoparticles have considerable application prospects as effective functional components of skin wound dressings due to their unique properties of conductivity,hydrophilicity,antibacterial activity,and biocompatibility. OBJECTIVE:To review the synthesis methods,functional properties,and application of MXene nanoparticles in skin injury repair. METHODS:"MXene,nanoparticles,nanomaterials,bioactive nanoparticles","wound dressing,wound dressing,wound repair materials","wound repair,wound healing,wound surface"were used as Chinese search terms to search Wanfang and CNKI databases."MXene,nanoparticles,nano-materials,bioactive nanoparticles","wound dressing,wound healing material","wound healing,wound repair,wound"were used as English search terms to search the PubMed database.Finally,88 articles were included for review analysis. RESULTS AND CONCLUSION:(1)MXene synthesis can be divided into two methods:bottom-up synthesis and top-down synthesis.The synthesized MXene can be further modified to enhance biocompatibility for better application in biomedicine.(2)MXene has a series of excellent properties such as hydrophilicity,antibacterial,photothermal properties,electrical conductivity,and good biocompatibility,all of which make it the basis for excellent skin repair materials.(3)At present,many scholars have developed new composite materials for wound dressings.Currently,these composite materials are based on MXene nanomaterials and make full use of its excellent characteristics as mentioned above,which play a role in local skin wound sterilization,drug delivery,and sustained release,active regulation of cytokines,and can integrate the advantages of other biologically active agents.It plays a better role in wound healing,especially in the treatment of complex chronic wounds.(4)Various composite materials such as MXene@PVA hydrogel and MXene@CH sponge developed based on various properties of MXene have shown good effects on improving tissue repair performance and repairing skin damage as drug carriers.It shows that MXenes nanoparticles are in the initial stage of development and have great prospects in the field of promoting skin repair.The characteristics and surface modification of MXenes nanoparticles have been well studied,but the molecular mechanism of dose-dependent biotoxicity is relatively incomplete.

ObjectiveTo observe the clinical efficacy and safety of Tinglu Yixin prescription in the treatment of patients with heart failure with preserved ejection fraction （HFpEF） combined with diabetes （syndromes of Qi and Yin deficiency and water retention and blood stasis） from taste-based compatibility and descending adverse Qi with bitter and pungent medicinals. MethodA total of 108 HFpEF patients with diabetes （syndromes of Qi and Yin deficiency and water retention and blood stasis） treated in the Nanjing Integrated Traditional Chinese and Western Medicine Hospital Affiliated to Nanjing University of Chinese Medicine from May 2022 to March 2023 were enrolled in this study and randomized into an observation group （54 patients） and a control group （54 patients）. Both groups received conventional Western medicine treatment according to the guide recommendations for chronic heart failure and diabetes， and the observation group additionally received Tinglu Yixin prescription. The treatment course for both groups was 12 weeks. The New York Heart Association （NYHA） grading of cardiac function， left ventricular end diastolic diameter （LVEDD）， left atrium diameter （LAD）， the ratio of early diastolic maximum mitral flow velocity （E） to early diastolic mitral annular motion velocity （e'） （E/e'）， N-terminal pro-B-type natriuretic peptide （NT-proBNP）， hemoglobin A1c （HbA1c）， 6-minute walking test （6MWT）， Minnesota Living with Heart Failure Questionnaire， traditional Chinese medicine （TCM） syndrome scores， and safety indicators were determined before and after treatment. ResultFinally， 104 patients were included for analysis， including 52 patients in the observation group and 52 patients in the control group. After treatment， 35 and 47 patients in the control and observation groups showed improved cardiac function， which indicated the total response rates of 67.3% and 90.4%， respectively. The total response rate regarding the cardiac function in the observation group was higher than that in the control group （χ²=2.754， P<0.05）. The observation group outperformed the control group in reducing LVEDD and LAD （P<0.05）， decreasing the E/e' ratio （P<0.05）， lowering the NT-proBNP and HbA1c levels （P<0.05）， and recovering the 6MWT and Minnesota quality of life score TCM syndrome scores （P<0.05）. None of the safety indicators in the two groups showed abnormal values before and after treatment， and no serious adverse reaction was observed. ConclusionTinglu Yixin prescription can improve the heart function， exercise tolerance， and quality of life， lower the HbA1c level， and alleviate the TCM syndrome in the patients with HFpEF combined with diabetes （syndrome of qi and yin deficiency and water stagnation and blood stasis）.