Objective:To discuss the role of changes of serum total bile acid(TBA)levels induced by long-term high-fat diet in the occurrence of supraventricular arrhythmia(SVA)in the apolipoprotein E knockout(ApoE-/-)mice,and to clarify its mechanism.Methods:Twenty ApoE-/-mice were randomly divided into normal diet group and high-fat diet(HFD)group(n=10);after 20 weeks of feeding,surface electrocardiogram was used to detect cardiac electrophysiology of the mice in various groups;echocardiography was used to detect cardiac systolic function and structure in the mice in various groups;enzyme-linked immunosorbent assay(ELISA)was used to detect serum levels of blood lipids,total bile acid(TBA)and inflammatory factors in the mice in various groups;hematoxylin-eosin(HE)staining was used to detect cardiac inflammatory response in the mice in various groups;Masson staining was used to observe myocardial fibrosis degree in the mice in various groups.Results:Compared with normal diet group,4 cases of junctional premature beat(JPB)/junctional tachycardia(JT),1 case of premature atrial contraction(PAC)and 1 case of premature ventricular contraction(PVC)were found in HFD group,while only 1 case of JPB/JT and 1 case of PAC were found in normal diet group.Compared with normal diet group,the heart rate of the mice in HFD group was significantly decreased(P<0.05);the QRS and QT intervals were significantly prolonged(P<0.05);the ejection fraction(EF)and fractional shortening(FS)were significantly decreased(P<0.05);the end-diastolic volume(EDV)was increased(P<0.05),but there was no significant difference in end-systolic volume(ESV)between groups(P>0.05);the left ventricular internal diameter at end-diastole(LVIDd)and left ventricular internal diameter at end-systole(LVIDs)were significantly increased(P<0.05).There were no significant differences in plasma total cholesterol(TC),triglyceride(TG),high-density lipoprotein(HDL-c)and low-density lipoprotein(LDL-c)levels and body weight between normal diet group and HFD group(P>0.05).Compared with normal diet group,the TBA level of the mice in HFD group was significantly increased(P<0.05).There were no significant differences in interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),monocyte chemoattractant protein-1(MCP-1),and C-X-C motif chemokine ligand 1(CXCL-1)levels between HFD group and normal diet group.Compared with normal diet group,the interleukin-1β(IL-1β)level in HFD group showed an increasing trend,but there was no significant difference between groups(P>0.05).The HE staining results showed that the inflammatory cell infiltration was similar between HFD group and normal diet group.The Masson staining results showed that compared with normal diet group,the fibrosis of the mice in HFD group showed an increasing trend,but there was no significant difference in myocardial fibrosis area between groups(P>0.05).Conclusion:Long-term high-fat diet may increase serum TBA level in ApoE-/-mice,which may induce SVA.

Allergic rhinitis (AR), a globally prevalent immune-mediated inflammatory condition, is still an incurable disease. In the present study, we have validated the impact of the Kelch-like ECH associated protein 1 (Keap1)-related oxidative stress and inflammatory response in clinical AR patient peripheral blood and nasal swab samples, emphasizing the biological relevance of Keap1 and AR. Targeting Keap1 -nuclear factor erythroid 2-related factor 2 (Nrf2) related anti-oxidative stress may be effective for AR intervention. Drawing inspiration from the Keap1 homodimerization and the E3 ligase characteristics, we herein present a design of novel bivalent molecules for chemical knockdown of Keap1. For the first time, we characterized ternary complexes of Keap1 dimer and one molecule of bivalent compounds. The best bivalent molecule 8 encompasses robust capacity to degrade Keap1 as a homoPROTAC^KEAP1. It efficaciously suppresses inflammatory cytokines in extensively different cells, including human nasal epithelial cells. Moreover, in an AR mouse model, we confirmed that the chemical degradation induced by homoPROTAC^KEAP1 led to therapeutic benefits in managing AR symptoms, oxidative stress and inflammation. In summary, our findings underscore the efficacy of targeting the Keap1 system through the homoPROTAC-ing technology as an innovative and promising treatment strategy for the incurable allergic disorders.

Objective To understand the current situation of healthcare-associated infection(HAI)in China,pro-vide data support and decision-making basis for formulating scientific and effective strategies for HAI prevention and control.Methods A nationwide cross-sectional survey on HAI was conducted among various types and levels of medical institutions in China according to a unified protocol of bedside surveys and case investigations.Results In 2024,a total of 5 736 medical institutions and 2 751 765 patients were surveyed.Among them,34 889 HAI cases were identified,with a prevalence rate of 1.27％.The number of HAI episodes was 38 032,and case prevalence rate was 1.38％.The prevalence rate of HAI in medical institutions in different regions of China ranged from 0.66％to 2.35％.Among medical institutions of different scales,those with a bed capacity of ≥900 had the high-est incidence of HAI,reaching 1.65％.The most common infection site was the lower respiratory tract(44.66％),followed by the urinary tract(12.94％),surgical site(9.32％),upper respiratory tract(7.02％),and bloodstream infection(5.78％).The top 3 departments with the highest HAI rates were the general intensive care unit(10.02％),department of neurosurgery(5.51％),and department(group)of hematology(5.34％).A total of 23 238 strains of HAI pathogens were detected,with 10 714 strains(46.10％)from lower respiratory tract speci-mens.The top 5 detected strains were Klebsiella pneumoniae(14.76％),Pseudomonas aeruginosa(13.33％),Escherichia coli(12.79％),Acinetobacter baumannii(9.23％),and Staphylococcus aureus(7.88％).231 944 pa-tients underwent class Ⅰ incision surgery were monitored,with 1 647 cases experienced surgical site infection,and the prevalence rate of surgical site infection was 0.71％.The number of patients who should undergo pathogen de-tection(patients receiving therapeutic and therapeutic combined prophylactic antimicrobial agents)was 715 179,while the actual number was 480 492,with a pathogen detection rate of 67.18％.425 225 patients received patho-genic detection before treatment,with a detection rate of 59.46％.Conclusion The overall HAI prevalence in Chi-na is lower,showing disparities among medical institutions of different regions and scales.Therefore,precise imple-mentation of measures is necessary for HAI prevention and control,with a focus on high-risk institutions and high-risk departments,key areas,and critical procedures.All levels of medical institutions should continuously reduce the incidence of HAI by strengthening monitoring,standardizing the use of antimicrobial agents,and reinforcing basic HAI prevention and control measures.

Objective:To analyze effects of T11TS in the treatment of Cryptococcus neoformans fungal infection and the regula-tion of T-cell calcineurin(CaN)-activated T lymphoid nuclear factor(NFAT)pathway.Methods:SD rats infected with Cryptococcus neoformans were treated with immunoenhancer T11TS.Flow cytometry,Western blot and nuclear translocation were used to detect the changes of T cell function and related signal pathway.Results:The number of Cryptococcus neoformans in lung and spleen of CT3 group was significantly less than Cryptococcus neoformans infection group,CT1 group and CT2 group(P<0.05).The results of flow cy-tometry showed that the expression levels of LCK,FYN,LAT,PLCγ1,CaN,NFAT and IL-2 in Cryptococcus neoformans infection group were significantly lower than control group(P<0.05).The expression levels of LCK,FYN,LAT,PLCγ1,CaN,NFAT and IL-2 of CT1,CT2 and CT3 groups were significantly higher than Cryptococcus neoformans infection group(P<0.05).The results of Western blot were similar to those of flow cytometry.Conclusion:T11TS in the treatment of Cryptococcus neoformans infection can enhance the immunity of the body by up-regulating the expression of related signal factors in the CaN-NFAT pathway of T lymphocytes,increasing the expression of NFAT and IL-2,stimulating the activation and proliferation of T lymphocytes.

Objective To explore the impact of the clinical internship model at the on-campus rehabilitation outpatient clinic on the clinical practice abilities and employment intentions of students in the physical therapy program.Methods A total of 60 students from the 2020 cohort of the Rehabilitation Physical Therapy program at Kunming Medical University were selected as research subjects.In the first semester of their sophomore year,they were randomly divided into two groups:the three-phase clinical internship group at the on-campus rehabilitation outpatient clinic(n=30)and the conventional clinical internship group(n=30).The three-phase clinical internship group completed their clinical internship in three phases according to the training objectives at the on-campus rehabilitation outpatient clinic,while the conventional clinical internship group completed their internship according to the requirements of the internship syllabus.At the end of all clinical internships,assessments were conducted using a comprehensive theoretical examination of core professional courses,the Assessment of Physiotherapy Practice(APP),and an employment intention survey to evaluate the outcomes of the internships for both groups.Results After completing all internship tasks,there was no statistically significant difference in the scores of the comprehensive theoretical examination of core professional courses between the two groups(P>0.05).Similarly,there was no statistically significant difference in the total scores of the physiotherapy clinical practice assessment between the two groups(P>0.05).However,in the detailed assessments,the three-phase internship group outperformed the conventional group in professional behavior,communication,and evaluation(P<0.05).There were no statistically significant differences between the two groups in analysis and planning,intervention,evidence-based practice,and risk management(P>0.05).In the employment intention survey,70%of students in the three-phase internship group expressed a willingness to work in rehabilitation outpatient clinics or clinics,while only 46.6%of the conventional group did so.The comparison of employment intentions between the two groups showed a statistically significant difference(P<0.05).Conclusion The three-phase apprenticeship model of the on-campus rehabilitation clinic not only improves students'clinical practice ability,but also increases their confidence in seeking employment in the rehabilitation clinic,thus broadening the employment pathway for physiotherapy students.

Objective:To summarize and analyze the clinical characteristics of patients with antibody mediated rejection (AMR) after lung transplantation at China-Japan Friendship Hospital, thereby providing references for clinical management.Methods:A retrospective study was conducted by collecting clinical data of 34 lung transplant recipients (LTRs) diagnosed with AMR between March 2017 and September 2023. The diagnosis of AMR was based on the 2019 International Society for Heart and Lung Transplantation (ISHLT) consensus. Baseline characteristics, primary diseases, pre-diagnostic events, diagnosis, treatment regimens, and outcomes were summarized and analyzed. According to outcomes at the final follow-up (March 31, 2024), patients were divided into survival group (22 cases) and death group (12 cases), and the differences in clinical characteristics and treatments were compared.Results:The incidence of AMR among 551 LTRs was 6.2% (34/551). Among the 34 AMR recipients, 79.4% (27/34) were male, and the median age was 64.0 (54.5, 67.3) years. The primary underlying disease was interstitial lung disease (79.4%). Based on diagnostic classification, 73.5%(25/34) were clinical AMR and 26.5% (9/34) were subclinical AMR. Regarding diagnostic levels, 11.8%(4/34) were proven AMR, 50.0% (17/34) probable AMR, and 38.2%(13/34) possible AMR. Pre-transplant sensitization was detected in 2 patients (5.9%). Post-transplant HLA antibody testing revealed 79.4%(27/34) positive for HLA class Ⅱ antibodies (most commonly DQ7) and 85.3%(29/34) had newly developed HLA antibodies, of which 82.4%(28/34) were de novo donor-specific antibodies (DSA). The most common clinical manifestations were exertional dyspnea(67.6%) and decreased pulse oxygen saturation(47.1%). Chest imaging mainly showed new consolidations or patchy opacities (55.9%), followed by ground-glass opacities (32.4%) and pleural effusion (20.6%). Regarding treatment, 94.1% (32/34) received intravenous immunoglobulin (IVIG), 88.2%(30/34) underwent plasma exchange, and 41.2%(14/34) received intravenous glucocorticoid (IVGC). The most common regimens were "plasma exchange+IVIG" and "IVGC+plasma exchange+IVIG+rituximab", each used in 23.5%(8/34) of cases. The complete HLA antibody clearance rate after treatment was 38.2%. The mortality rates at 3 months, 1 year, and final follow-up after AMR diagnosis were 8.8%, 23.5%, and 35.3%, respectively, with a median survival time of 243.0(96.3, 572.3) days. The survival group had a significantly higher rate of tacrolimus-based triple immunosuppressive therapy (glucocorticoid+tacrolimus+mycophenolate moftil) compared to the death group [86.4% (19/22) vs 50.0% (6/12), P=0.040], while rituximab usage was higher in the death group [75.0% (9/12) vs 13.6% (3/22), P=0.008]. Conclusions:Although AMR after lung transplantation is relatively rare, its diagnosis is challenging, antibody clearance rate after treatment is low, and clinical outcomes are poor, requiring heightened clinical vigilance.

Objective:To analyze effects of T11TS in the treatment of Cryptococcus neoformans fungal infection and the regula-tion of T-cell calcineurin(CaN)-activated T lymphoid nuclear factor(NFAT)pathway.Methods:SD rats infected with Cryptococcus neoformans were treated with immunoenhancer T11TS.Flow cytometry,Western blot and nuclear translocation were used to detect the changes of T cell function and related signal pathway.Results:The number of Cryptococcus neoformans in lung and spleen of CT3 group was significantly less than Cryptococcus neoformans infection group,CT1 group and CT2 group(P<0.05).The results of flow cy-tometry showed that the expression levels of LCK,FYN,LAT,PLCγ1,CaN,NFAT and IL-2 in Cryptococcus neoformans infection group were significantly lower than control group(P<0.05).The expression levels of LCK,FYN,LAT,PLCγ1,CaN,NFAT and IL-2 of CT1,CT2 and CT3 groups were significantly higher than Cryptococcus neoformans infection group(P<0.05).The results of Western blot were similar to those of flow cytometry.Conclusion:T11TS in the treatment of Cryptococcus neoformans infection can enhance the immunity of the body by up-regulating the expression of related signal factors in the CaN-NFAT pathway of T lymphocytes,increasing the expression of NFAT and IL-2,stimulating the activation and proliferation of T lymphocytes.

Objective To understand the current situation of healthcare-associated infection(HAI)in China,pro-vide data support and decision-making basis for formulating scientific and effective strategies for HAI prevention and control.Methods A nationwide cross-sectional survey on HAI was conducted among various types and levels of medical institutions in China according to a unified protocol of bedside surveys and case investigations.Results In 2024,a total of 5 736 medical institutions and 2 751 765 patients were surveyed.Among them,34 889 HAI cases were identified,with a prevalence rate of 1.27％.The number of HAI episodes was 38 032,and case prevalence rate was 1.38％.The prevalence rate of HAI in medical institutions in different regions of China ranged from 0.66％to 2.35％.Among medical institutions of different scales,those with a bed capacity of ≥900 had the high-est incidence of HAI,reaching 1.65％.The most common infection site was the lower respiratory tract(44.66％),followed by the urinary tract(12.94％),surgical site(9.32％),upper respiratory tract(7.02％),and bloodstream infection(5.78％).The top 3 departments with the highest HAI rates were the general intensive care unit(10.02％),department of neurosurgery(5.51％),and department(group)of hematology(5.34％).A total of 23 238 strains of HAI pathogens were detected,with 10 714 strains(46.10％)from lower respiratory tract speci-mens.The top 5 detected strains were Klebsiella pneumoniae(14.76％),Pseudomonas aeruginosa(13.33％),Escherichia coli(12.79％),Acinetobacter baumannii(9.23％),and Staphylococcus aureus(7.88％).231 944 pa-tients underwent class Ⅰ incision surgery were monitored,with 1 647 cases experienced surgical site infection,and the prevalence rate of surgical site infection was 0.71％.The number of patients who should undergo pathogen de-tection(patients receiving therapeutic and therapeutic combined prophylactic antimicrobial agents)was 715 179,while the actual number was 480 492,with a pathogen detection rate of 67.18％.425 225 patients received patho-genic detection before treatment,with a detection rate of 59.46％.Conclusion The overall HAI prevalence in Chi-na is lower,showing disparities among medical institutions of different regions and scales.Therefore,precise imple-mentation of measures is necessary for HAI prevention and control,with a focus on high-risk institutions and high-risk departments,key areas,and critical procedures.All levels of medical institutions should continuously reduce the incidence of HAI by strengthening monitoring,standardizing the use of antimicrobial agents,and reinforcing basic HAI prevention and control measures.

Objective:To summarize and analyze the clinical characteristics of patients with antibody mediated rejection (AMR) after lung transplantation at China-Japan Friendship Hospital, thereby providing references for clinical management.Methods:A retrospective study was conducted by collecting clinical data of 34 lung transplant recipients (LTRs) diagnosed with AMR between March 2017 and September 2023. The diagnosis of AMR was based on the 2019 International Society for Heart and Lung Transplantation (ISHLT) consensus. Baseline characteristics, primary diseases, pre-diagnostic events, diagnosis, treatment regimens, and outcomes were summarized and analyzed. According to outcomes at the final follow-up (March 31, 2024), patients were divided into survival group (22 cases) and death group (12 cases), and the differences in clinical characteristics and treatments were compared.Results:The incidence of AMR among 551 LTRs was 6.2% (34/551). Among the 34 AMR recipients, 79.4% (27/34) were male, and the median age was 64.0 (54.5, 67.3) years. The primary underlying disease was interstitial lung disease (79.4%). Based on diagnostic classification, 73.5%(25/34) were clinical AMR and 26.5% (9/34) were subclinical AMR. Regarding diagnostic levels, 11.8%(4/34) were proven AMR, 50.0% (17/34) probable AMR, and 38.2%(13/34) possible AMR. Pre-transplant sensitization was detected in 2 patients (5.9%). Post-transplant HLA antibody testing revealed 79.4%(27/34) positive for HLA class Ⅱ antibodies (most commonly DQ7) and 85.3%(29/34) had newly developed HLA antibodies, of which 82.4%(28/34) were de novo donor-specific antibodies (DSA). The most common clinical manifestations were exertional dyspnea(67.6%) and decreased pulse oxygen saturation(47.1%). Chest imaging mainly showed new consolidations or patchy opacities (55.9%), followed by ground-glass opacities (32.4%) and pleural effusion (20.6%). Regarding treatment, 94.1% (32/34) received intravenous immunoglobulin (IVIG), 88.2%(30/34) underwent plasma exchange, and 41.2%(14/34) received intravenous glucocorticoid (IVGC). The most common regimens were "plasma exchange+IVIG" and "IVGC+plasma exchange+IVIG+rituximab", each used in 23.5%(8/34) of cases. The complete HLA antibody clearance rate after treatment was 38.2%. The mortality rates at 3 months, 1 year, and final follow-up after AMR diagnosis were 8.8%, 23.5%, and 35.3%, respectively, with a median survival time of 243.0(96.3, 572.3) days. The survival group had a significantly higher rate of tacrolimus-based triple immunosuppressive therapy (glucocorticoid+tacrolimus+mycophenolate moftil) compared to the death group [86.4% (19/22) vs 50.0% (6/12), P=0.040], while rituximab usage was higher in the death group [75.0% (9/12) vs 13.6% (3/22), P=0.008]. Conclusions:Although AMR after lung transplantation is relatively rare, its diagnosis is challenging, antibody clearance rate after treatment is low, and clinical outcomes are poor, requiring heightened clinical vigilance.

Nuclear receptor corepressor (NCoR1) interacts with various nuclear receptors and regulates the anabolism and catabolism of lipids. An imbalance in lipid/energy homeostasis is also an important factor in obesity and metabolic syndrome development. In this study, we found that the deletion of NCoR1 in intestinal epithelial cells (IECs) mainly activated the nuclear receptor PPARα and attenuated metabolic syndrome by stimulating thermogenesis. The increase in brown adipose tissue thermogenesis was mediated by gut-derived tricarboxylic acid cycle intermediate succinate, whose production was significantly enhanced by PPARα activation in the fed state. Additionally, NCoR1 deletion derepressed intestinal LXR, increased cholesterol excretion, and impaired duodenal lipid absorption by decreasing bile acid hydrophobicity, thereby reversing the possible negative effects of intestinal PPARα activation. Therefore, the simultaneous regulatory effect of intestinal NCoR1 on both lipid intake and energy expenditure strongly suggests that it is a promising target for developing metabolic syndrome treatment.