A 51-year-old male presented with nasal obstruction, followed by progressive hearing loss and blurred vision. Imaging identified space-occupying lesions in the paranasal sinuses, orbits, and paraspinal regions, while laboratory tests confirmed positive anti-proteinase 3 anti-neutrophil cytoplasmic antibody(PR3- ANCA) immunoglobulin G (IgG)and markedly elevated serum IgG4. Despite treatment with corticosteroids, immunosuppressants, and radiotherapy, the patient exhibited steroid dependency with relentless disease progression. Following multidisciplinary consultation, a diagnosis of inflammatory myofibroblastic tumor (IMT) coexisting with ANCA- associated vasculitis (AAV) was favored, though IgG4-related disease remained a critical differential. Ultimately, profound immunosuppression precipitated a severe herpesvirus infection, leading to disseminated intravascular coagulation and multiple organ dysfunction syndrome. This case underscores the rarity and diagnostic complexity of concurrent IMT and AAV, highlights the therapeutic dilemma of balancing primary disease control against fatal opportunistic infections, and emphasizes the critical role of multidisciplinary collaboration in the diagnosis and treatment of complex diseases.

Objective To comprehensively evaluate the multidimensional impact of the"Tianjin Experience"of Chest Pain Center(CPC)development on in-hospital mortality,optimization of treatment workflows,and regional coordination of care for patients with acute myocardial infarction(AMI),with the aim of providing scientific evidence to further improve the model and enhance AMI treatment outcomes.Methods This study analyzed data from the"Cardiovascular and Cerebrovascular Acute Events Surveillance System"maintained by the Tianjin Center for Disease Control and Prevention from 2013 to 2024.A segmented regression model was applied to assess the long-term trends in in-hospital mortality from acute myocardial infarction(AMI),with a particular focus on evaluating the impact of the chest pain center program on treatment outcomes.Additionally,supplementary analyses were conducted using surveillance data from the Tianjin Chest Pain Center Quality Control Team between 2017 and 2024.To verify the effectiveness of treatment process optimization,temporal trends in key time-based process indicators were assessed,including Door-in-Door-out(DIDO)time at non-PCI hospitals,Door-to-Wire(D-to-W)time,and First Medical Contact to Wire(FMC-to-W)to wire time.Results According to the data from the Tianjin Center for Disease Control and Prevention,the average 28-day AMI mortality rate in the overall patient population was 9.85％.Between 01/2013 and 12/2014,the mortality rate showed a significant upward trend(P＜0.01),followed by a downward trend from 01/2015 to 12/2024,although the latter did not reach statistical significance(P＞0.05).From 2013 to 2024,a total of 27 633 AMI cases with complete clinical records were collected from Tianjin Chest Hospital,with an average 28-day mortality rate of 4.55％.The mortality rate exhibited a decreasing trend from 01/2013 to 12/2016,with an annual percent change(APC)of-7.56(P＜0.05).From 01/2017 to 12/2024,the trend stabilized,with an APC of 0.39(P＞0.05).Conclusions The development of the CPC system in Tianjin significantly reduced key treatment times and improved the overall efficiency of AMI management.While population-level AMI mortality rates began to decline after 2015,the rate of improvement has slowed,indicating a continued need for optimizing the regional coordinated care system to further enhance patient outcomes.

Aim To elucidate the molecular mecha-nism underlying the inhibitory effect of liquidambaric acid(LDA)targeting TNF receptor associated factor 6(TRAF6)in colorectal cancer.Methods This study employed microscale thermophoresis(MST),drug af-finity responsive target stability assay(DARTS)and cellular thermal shift assay(CETSA)to confirm the direct binding of LDA to TRAF6.Additionally,we generated TRAF6 knockout colorectal cancer HCT116 cells using CRISPR/Cas9 technology,and assessed the impact of LDA on TRAF6-regulated Hippo/YAP and Wnt signaling pathways through immunofluorescence a-nalysis and TOPFlash/Renilla luciferase reporter sys-tem.Co-IP and proximity ligation assays(PLA)were conducted to investigate LDA-regulated TRAF6 pro-tein-protein interactions and elucidate molecular mech-anisms.Results The direct binding of LDA to TRAF6 was confirmed in cell lysates and living cells.LDA promoted TRAF6-dependent nuclear translocation of YAP in colorectal cancer cells,and inhibited Wnt signaling by overexpressing TRAF6.Co-IP and PLA revealed that TRAF6 formed a tripartite complex with YAP and β-catenin in colon cancer cells,where TRAF6 was a key scaffolding protein of the tripartite complex.LDA disrupted the interactions between the TRAF domain of TRAF6 and YAP,as well as YAP and β-catenin.Conclusion LDA regulates Hippo/YAP signaling pathway by targeting TRAF6 and inhib-its colorectal cancer.

A 15-year-old boy developed abdominal pain and melena two weeks after COVID-19 infection, which was followed by gross hematuria and proteinuria. Laboratory studies revealed significantly elevated inflammatory markers. Endoscopic examinations showed multiple jejunal and ileal ulcers. Renal biopsy suggested mesangial proliferative glomerulonephritis with crescent formation, necrosis of capillary loops, and mesangial IgA deposits. IgA vasculitis without purpura was considered as a possible diagnosis, and the treatment with prednisone led to remission of both gastrointestinal and renal diseases.

Objective To explore the impact of peptidylarginine deiminase 2(Padi2)-knockout on depressive-like behaviors in socially isolated mice.Methods Using CRISPR/Cas9 technology,a Padi2-knockout(Padi2-/-)mouse model with a C57BL/6J background was established,and the effect of Padi2 knockout was identified by genotyping and RT-qPCR detection.Six-week-old male Padi2-/- mice and wild-type C57BL/6J mice were selected and divided into normal rearing and social isolation groups,with 15 mice per group.The normal rearing group mice were housed with 5 mice per cage,and the social isolation group was housed with 1 mouse per cage,and weighed once a week.After 4 weeks,forced swimming and open field tests were conducted.After the behavioral experiments,brain tissues were taken from mice in each group,and changes in microglia in the brains were detected by immunofluorescence.Results We successfully established Padi2-/- mice.There was no difference in behavior between Padi2-/- mice and C57BL/6J mice in the normal rearing group.After social isolation,compared with C57BL/6J mice,Padi2-/- mice showed a significant increase in depressive symptoms,obvious weight gain,and a significant increase in the number of microglia in brain tissue.Conclusions Padi2 knockout exacerbated depressive-like behaviors and obesity in socially isolated mice,indicating that Padi2 is involved in the progression of depression and may be an effective target for the prevention and treatment of depression.

Objective This study aims to explore the association between non-suicidal self-injury(NSSI)and suicide attempts(SA)in adolescents and the mediating effect of cognitive flexibility.Methods A total of 218 depression patients with NSSI who met the Diagnostic and Statistical Manual of Mental Disorders,5th Edition(DSM-5)diagnostic criteria for NSSI were enrolled.Patients were divided into SA group(n=105)and non-SA group(n=113)according to the presence or absence of SA in the last one year.The adolescent non-suicidal self-injury assessment questionnaire(ANSAQ)and the Wisconsin card sorting tests(WCST)was used to assess the frequency of NSSI and cognitive flexibility,respectively.A mediation model was constructed to conduct path analysis,and the product distribution method was utilized to test the mediation effect.Results The difference between SA group and non-SA group in NSSI(20.1±10.7 vs.14.7±9.1)and WCST scores[correct responses percentage(67.3％±14.2％vs.72.9％±12.2％),error responses(39.8±20.3 vs.31.6±17.9),perseverative response(6.7±3.8 vs.5.3±2.9),and non-perseverative errors(37.6±21.0 vs.28.9±18.1)]were significant(P<0.05).Dichotomous logistic regression analysis showed that the frequency of NSSI(OR=1.051,95％CI:1.021-1.082)and the score of perseverative response(OR=1.100,95％CI:1.008-1.199)were significantly associated with suicidal behavior among adolescents with NSSI(P<0.05).Moreover,perseverative response partially mediated the association between NSSI and SA(95％CI of Za×Zb:0.0003-0.0168).Conclusion High NSSI and low cognitive flexibility are risk factors for suicide attempts in NSSI adolescents and NSSI may also affect SA indirectly by lowering cognitive flexibility.

Objective To comprehensively evaluate the multidimensional impact of the"Tianjin Experience"of Chest Pain Center(CPC)development on in-hospital mortality,optimization of treatment workflows,and regional coordination of care for patients with acute myocardial infarction(AMI),with the aim of providing scientific evidence to further improve the model and enhance AMI treatment outcomes.Methods This study analyzed data from the"Cardiovascular and Cerebrovascular Acute Events Surveillance System"maintained by the Tianjin Center for Disease Control and Prevention from 2013 to 2024.A segmented regression model was applied to assess the long-term trends in in-hospital mortality from acute myocardial infarction(AMI),with a particular focus on evaluating the impact of the chest pain center program on treatment outcomes.Additionally,supplementary analyses were conducted using surveillance data from the Tianjin Chest Pain Center Quality Control Team between 2017 and 2024.To verify the effectiveness of treatment process optimization,temporal trends in key time-based process indicators were assessed,including Door-in-Door-out(DIDO)time at non-PCI hospitals,Door-to-Wire(D-to-W)time,and First Medical Contact to Wire(FMC-to-W)to wire time.Results According to the data from the Tianjin Center for Disease Control and Prevention,the average 28-day AMI mortality rate in the overall patient population was 9.85％.Between 01/2013 and 12/2014,the mortality rate showed a significant upward trend(P＜0.01),followed by a downward trend from 01/2015 to 12/2024,although the latter did not reach statistical significance(P＞0.05).From 2013 to 2024,a total of 27 633 AMI cases with complete clinical records were collected from Tianjin Chest Hospital,with an average 28-day mortality rate of 4.55％.The mortality rate exhibited a decreasing trend from 01/2013 to 12/2016,with an annual percent change(APC)of-7.56(P＜0.05).From 01/2017 to 12/2024,the trend stabilized,with an APC of 0.39(P＞0.05).Conclusions The development of the CPC system in Tianjin significantly reduced key treatment times and improved the overall efficiency of AMI management.While population-level AMI mortality rates began to decline after 2015,the rate of improvement has slowed,indicating a continued need for optimizing the regional coordinated care system to further enhance patient outcomes.

Aim To elucidate the molecular mecha-nism underlying the inhibitory effect of liquidambaric acid(LDA)targeting TNF receptor associated factor 6(TRAF6)in colorectal cancer.Methods This study employed microscale thermophoresis(MST),drug af-finity responsive target stability assay(DARTS)and cellular thermal shift assay(CETSA)to confirm the direct binding of LDA to TRAF6.Additionally,we generated TRAF6 knockout colorectal cancer HCT116 cells using CRISPR/Cas9 technology,and assessed the impact of LDA on TRAF6-regulated Hippo/YAP and Wnt signaling pathways through immunofluorescence a-nalysis and TOPFlash/Renilla luciferase reporter sys-tem.Co-IP and proximity ligation assays(PLA)were conducted to investigate LDA-regulated TRAF6 pro-tein-protein interactions and elucidate molecular mech-anisms.Results The direct binding of LDA to TRAF6 was confirmed in cell lysates and living cells.LDA promoted TRAF6-dependent nuclear translocation of YAP in colorectal cancer cells,and inhibited Wnt signaling by overexpressing TRAF6.Co-IP and PLA revealed that TRAF6 formed a tripartite complex with YAP and β-catenin in colon cancer cells,where TRAF6 was a key scaffolding protein of the tripartite complex.LDA disrupted the interactions between the TRAF domain of TRAF6 and YAP,as well as YAP and β-catenin.Conclusion LDA regulates Hippo/YAP signaling pathway by targeting TRAF6 and inhib-its colorectal cancer.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective:To explore the molecular mechanism by which adipose-derived mesenchymal stem cell exosomes (ADSC-Exos) inhibit hypertrophic scars (HS), and to identify the key functional miRNA and its downstream signaling pathway.Methods:A mouse model of hypertrophic scars was established by subcutaneous injection of bleomycin. The dorsal fibrotic modeling area was intervened with human ADSC-Exos (ADSC-Exos group), while the control group was injected with the same volume of PBS. HE and Masson staining were used to evaluate the morphological changes and collagen deposition of skin scar tissue in the two groups. Immunohistochemistry was performed to detect the expression of collagen 1 (Col-1) and α-smooth muscle actin (α-SMA). Western blot was used to determine the expression levels of key proteins in the transforming growth factor-β1 (TGF-β1)/Smad pathway (p-Smad2/3, Smad2/3). RNA sequencing datasets from the public database (GEO) were downloaded to analyze and screen differentially expressed miRNAs after ADSC-Exos treatment. In vitro cultured human hypertrophic scar fibroblasts (HSF) were transfected with miR-376b-5p mimic or inhibitor on the basis of ADSC-Exos treatment, and the expression of fibrosis markers (Col-1, α-SMA) as well as p-Smad2/3 and Smad2/3 was detected.Results:In vivo experiments showed that ADSC-Exos treatment significantly improved the fibrotic phenotype of mouse scar tissue, reduced the expression of Col-1 and α-SMA, and decreased the phosphorylation of Smad2/3 protein. Bioinformatics analysis revealed that miR-376b-5p was one of the most significantly upregulated miRNAs after ADSC-Exos treatment. In vitro experiments confirmed that overexpression of miR-376b-5p could mimic the antifibrotic effect of ADSC-Exos, significantly inhibit the expression of Col-1 and α-SMA in HSF, and reduce the phosphorylation level of Smad2/3. Specific inhibition of miR-376b-5p could effectively reverse the inhibitory effect of ADSC-Exos on the fibrotic phenotype of HSF and the phosphorylation of Smad2/3.Conclusions:This study reveals that ADSC-Exos exert their antifibrotic effect by mediating miR-376b-5p to target and inhibit the activation of the TGF-β1/Smad signaling pathway. miR-376b-5p is a key functional molecule in ADSC-Exos, and this finding provides a new potential target for the treatment of HS.