Background/Aims: Cholangiocarcinoma (CCA) is a primary malignant neoplasm with an extremely poor prognosis. While combined chemoradiotherapy has been demonstrated to delay CCA progression to a certain extent, the absence of specific molecular biomarkers or targets significantly hinders the diagnosis and treatment of CCA. Methods: Through cross-analysis of proteomics and ADMA modificationomics, we identified DDX1 overexpressed in CCA with elevated R602-ADMA modifications. HPLC-MS/MS identified PRMT1 as the methyltransferase and USP10 as the deubiquitinating enzyme for DDX1. Immunofluorescence and nuclear-cytoplasmic partitioning experiments confirmed DDX1’s nuclear localization. GO and KEGG analyses clarify the biological functions of DDX1 in response to hypoxia. RNA-seq transcriptomics analyzed key pathways influenced by DDX1. A hydrodynamic in situ CCA mouse model was established to validate the chemopreventive effects of the PRMT1-specific inhibitor GSK715 on CCA development. Results: DDX1 promotes CCA progression both in vivo and in vitro and can be inhibited by GSK715. Mechanistically, PRMT1 mediates ADMA modification at position R602 of DDX1. This modification promotes DDX1 nuclear localization by recruiting USP10 to deubiquitinate DDX1, while simultaneously inhibiting PRMT1 degradation. DDX1 promotes the transcription of PRMT1 and USP10 by binding to the mRNA 3’UTR region, establishing a positive feedback regulatory pathway. This mechanism promotes the occurrence and development of CCA and can serve as a target for the inhibitor GSK715 to suppress CCA progression. Conclusions Our study identified DDX1-R602-ADMA modification as a novel ADMA modification in CCA. It further confirmed its pivotal role in CCA progression. Targeting the USP10-PRMT1-DDX1 axis may represent a significant therapeutic approach for CCA.

Objective Under the operation background of Diagnosis-Intervention Packet(DIP),whether there is interaction between reducing medical cost and average length of stay combined with pre-hospitalization mode,and whether there is difference between different departments and diseases in interaction.Methods Based on real-world data from 71 453 patients admitted to Guizhou Provincial People's Hospital from July to December 2021,a two-way analysis of variance was employed.When the interaction effect was statistically significant,parameter estimation was used to determine the magnitude and direction of the interaction effect,followed by subgroup analyses by department and disease.Results Without adjustment,both total medical costs and average length of stay exhibited a negative interaction effect(P＜0.05).Subgroup analyses revealed that in terms of total medical costs,the effect size for the surgical system was 0.18％,lower than that for the internal medicine system(0.70％);for core diseases,it was 6.62％,lower than that for comprehensive diseases(7.71％).Regarding average length of stay,the effect size for the surgical system was 0.55％,better than that for the internal medicine system(0.22％);for core diseases,it was 8.70％,higher than that for comprehensive diseases(2.90％).Conclusion The combination of DIP payment reform and pre-admission management model demonstrates a synergistic effect,effectively reducing patients' medical costs and length of stay.This effect is influenced by disease complexity and the standardization of diagnostic and treatment processes.

OBJECTIVE To investigate the clinical distribution and dynamic change of drug resistance of K.pneu-moniae and carbapenem-resistant Klebsiella pneumoniae(CRKP)isolated from a three-A hospital of Suzhou so as to provide scientific bases for prevention and control of hospital-associated infections and reasonable application of antibiotics.METHODS The K.pneumoniae and CRKP strains that were isolated from the submitted specimens were collected from the patients who treated in the Affiliated Suzhou Hospital of Nanjing Medical University from 2019 to 2023.The clinical characteristics of the patients with infection and the trend of drug resistance were statis-tically analyzed.RESULTS Totally 5631 strains of K.pneumoniae were isolated,1205(21.40％)of which were CRKP,and the isolation rate of CRKP showed an upward trend in the five years(x2=236.352,P＜0.001).Among the K.pneumoniae isolates,51.59％were isolated from sputum,13.51％from urine;19.43％were isolated from intensive care unit(ICU),7.64％from emergency department,and 7.19％from respiratory department.There were significant differences in gender,age and season between the patients detected with CRKP and the patients detected with non-CRKP(P＜0.05).The drug resistance rates of the K.pneumoniae strains to cephalosporins,quinolones and carbapenems con-tinuously increased from 2019 to 2023(P＜0.001),the drug resistance rate to imipenem increased from 11.69％to 34.24％,meropenem from 10.92％to 34.24％.CONCLUSIONS The K.pneumoniae isolates show severe drug re-sistance from 2019 to 2023,and the isolation rate of CRKP strains rises increasingly.It is necessary for the hospi-tal to focus on the continuous monitoring of key populations and departments and optimize the management of an-tibiotics and infection control strategies so as to provide guidance for reasonable clinical use of antibiotics,effective control of transmission of drug-resistant strains and cope with the increasingly severe drug resistance.

Objective Under the operation background of Diagnosis-Intervention Packet(DIP),whether there is interaction between reducing medical cost and average length of stay combined with pre-hospitalization mode,and whether there is difference between different departments and diseases in interaction.Methods Based on real-world data from 71 453 patients admitted to Guizhou Provincial People's Hospital from July to December 2021,a two-way analysis of variance was employed.When the interaction effect was statistically significant,parameter estimation was used to determine the magnitude and direction of the interaction effect,followed by subgroup analyses by department and disease.Results Without adjustment,both total medical costs and average length of stay exhibited a negative interaction effect(P＜0.05).Subgroup analyses revealed that in terms of total medical costs,the effect size for the surgical system was 0.18％,lower than that for the internal medicine system(0.70％);for core diseases,it was 6.62％,lower than that for comprehensive diseases(7.71％).Regarding average length of stay,the effect size for the surgical system was 0.55％,better than that for the internal medicine system(0.22％);for core diseases,it was 8.70％,higher than that for comprehensive diseases(2.90％).Conclusion The combination of DIP payment reform and pre-admission management model demonstrates a synergistic effect,effectively reducing patients' medical costs and length of stay.This effect is influenced by disease complexity and the standardization of diagnostic and treatment processes.

Objective To investigate the value of diffusion kurtosis imaging(DKI)in the differential diagnosis between benign and malignant sinonasal lesions.Methods The clinical and imaging data of 49 patients(20 benign and 29 malignant lesions)with sinonasal lesions confirmed by surgery and pathology were analyzed retrospectively.Conventional MRI and DKI were scanned for all patients.DKI quantitative parameters,including D-value and K-value,were measured by using FireVoxel software.The t-test was used to compare the differences of D-value and K-value between benign and malignant lesions.Diagnostic performances of these parameters and their combination in differentiating benign from malignant sinonasal lesions were assessed by using receiver operating characteristic(ROC)curve.Results Compared with benign group,malignant group showed significantly lower D-value(1.354±0.329 vs 1.924±0.595,P＜0.001)and higher K-value(0.856±0.190 vs 0.630±0.165,P＜0.001).ROC curve analysis showed that the area under the curve(AUC)for D-value in differentiating benign from malignant lesions was 0.820,with a cut-off value of＜1.775,sensitivity of 93.10％,and specificity of 55.00％.The AUC for K-value was 0.831,with a cut-off value of＞0.716,sensitivity of 79.31％,and specificity of 80.00％.The model combining D-value and K-value achieved an AUC of 0.859,sensitivity of 93.10％,and specificity of 70.00％.Conclusion The D-value and K-value obtained based on DKI can provide significant assistance in differentiating benign from malignant sinonasal lesions.

OBJECTIVE To investigate the clinical distribution and dynamic change of drug resistance of K.pneu-moniae and carbapenem-resistant Klebsiella pneumoniae(CRKP)isolated from a three-A hospital of Suzhou so as to provide scientific bases for prevention and control of hospital-associated infections and reasonable application of antibiotics.METHODS The K.pneumoniae and CRKP strains that were isolated from the submitted specimens were collected from the patients who treated in the Affiliated Suzhou Hospital of Nanjing Medical University from 2019 to 2023.The clinical characteristics of the patients with infection and the trend of drug resistance were statis-tically analyzed.RESULTS Totally 5631 strains of K.pneumoniae were isolated,1205(21.40％)of which were CRKP,and the isolation rate of CRKP showed an upward trend in the five years(x2=236.352,P＜0.001).Among the K.pneumoniae isolates,51.59％were isolated from sputum,13.51％from urine;19.43％were isolated from intensive care unit(ICU),7.64％from emergency department,and 7.19％from respiratory department.There were significant differences in gender,age and season between the patients detected with CRKP and the patients detected with non-CRKP(P＜0.05).The drug resistance rates of the K.pneumoniae strains to cephalosporins,quinolones and carbapenems con-tinuously increased from 2019 to 2023(P＜0.001),the drug resistance rate to imipenem increased from 11.69％to 34.24％,meropenem from 10.92％to 34.24％.CONCLUSIONS The K.pneumoniae isolates show severe drug re-sistance from 2019 to 2023,and the isolation rate of CRKP strains rises increasingly.It is necessary for the hospi-tal to focus on the continuous monitoring of key populations and departments and optimize the management of an-tibiotics and infection control strategies so as to provide guidance for reasonable clinical use of antibiotics,effective control of transmission of drug-resistant strains and cope with the increasingly severe drug resistance.

Objective To investigate the value of diffusion kurtosis imaging(DKI)in the differential diagnosis between benign and malignant sinonasal lesions.Methods The clinical and imaging data of 49 patients(20 benign and 29 malignant lesions)with sinonasal lesions confirmed by surgery and pathology were analyzed retrospectively.Conventional MRI and DKI were scanned for all patients.DKI quantitative parameters,including D-value and K-value,were measured by using FireVoxel software.The t-test was used to compare the differences of D-value and K-value between benign and malignant lesions.Diagnostic performances of these parameters and their combination in differentiating benign from malignant sinonasal lesions were assessed by using receiver operating characteristic(ROC)curve.Results Compared with benign group,malignant group showed significantly lower D-value(1.354±0.329 vs 1.924±0.595,P＜0.001)and higher K-value(0.856±0.190 vs 0.630±0.165,P＜0.001).ROC curve analysis showed that the area under the curve(AUC)for D-value in differentiating benign from malignant lesions was 0.820,with a cut-off value of＜1.775,sensitivity of 93.10％,and specificity of 55.00％.The AUC for K-value was 0.831,with a cut-off value of＞0.716,sensitivity of 79.31％,and specificity of 80.00％.The model combining D-value and K-value achieved an AUC of 0.859,sensitivity of 93.10％,and specificity of 70.00％.Conclusion The D-value and K-value obtained based on DKI can provide significant assistance in differentiating benign from malignant sinonasal lesions.

This study was aimed at exploring the epidemic characteristics and spatio-temporal evolution patterns of severe fever with thrombocytopenia syndrome(SFTS)in Henan Province from 2011 to 2022,to provide a reference for prevention and control ef-forts.Data on SFTS in Henan Province from 2011 to 2022 were collected from the Information Management System for Infectious Dis-ease Reporting,and epidemiological characteristics and spatio-temporal evolution patterns were investigated through spatial autocorre-lation analysis,standard deviation ellipse analysis,and spatial-centered transfer curves,on a district-county basis.From 2011 to 2022,a total of 5 471 SFTS cases associated with 81 deaths were reported in Henan Province.The incidence rate showed an increasing trend(χ2trend=23.24,P<0.001),and the average annual incidence was 0.4 677/100 000.The case-fatality rate showed a decreasing trend from 2011 to 2019(χ2trend=8.86,P=0.003),but an increasing trend from 2020 to 2022(χ2trend=12.93,P<0.001).The average an-nual case-fatality rate was 1.48%.The peak incidence period was from May to July;this period accounted for 58.75%of the total cases.Females(59.39%),individuals 60-80 years old(55.40%),and farmers(96.64%)were the high prevalence groups.The disease was distributed primarily in Xinyang City,and Shangcheng County had the highest incidence rate(27.411 8/100 000).Spatial aggregation was observed in the southeastern region(Moran's I>0,P<0.001),and the disease centers were all located in Guangshan County,Xin-yang City,and showed southeast-northwest-southeast-northwest-southeast-northeast-southwest movement during the 12-year pe-riod.In conclusion,from 2011 to 2022,SFTS in Henan Province had a high incidence in May to July,and females,older people,and farmers were the high-risk groups.Spatial aggregation was observed in the southeastern region,along with spread to surrounding areas.Xinyang City is therefore a key area for the prevention and control of SFTS.

Objective:To evaluate the accuracy of p53 immunohistochemistry for predicting the mutational status of TP53 in gliomas.Methods:A retrospective study was conducted on 242 diffuse gliomas diagnosed at the Department of Pathology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China from June 2022 to March 2023. All cases underwent next-generation sequencing (NGS) and p53 immunohistochemical staining. The best threshold in the percentage of p53 immunohistochemical expression was assessed as an alternative to testing for TP53 mutation.Results:Among the 242 diffuse gliomas (WHO grade 2-4), 94 cases had a TP53 mutation. The p53 immunohistochemistry results revealed a significantly increased probability of TP53 mutation when the p53 immunohistochemical positivity rate (based on strongly positive cell count) was ≥20% ( P<0.05). The sensitivity and specificity of p53 immunohistochemistry for predicting TP53 gene mutations were 75.6% and 90.4%, respectively. When p53 immunohistochemical stain was totally negative, the probability of TP53 mutation increased significantly, and the mutation ratio of TP53 gene was 6/17 in all negative cases. Conclusions:When the percentage of p53 positive cells (based on strongly positive cell count) in glioma is ≥20%, p53 immunohistochemistry can be used as a reliable alternative method for TP53 mutation detection. When p53 immunohistochemistry is completely negative, the mutation rate of TP53 gene is higher, and further gene sequencing is recommended to determine the mutation status.

Objective To evaluate the comprehensive value of methicillin-resistant Staphylococcus aureus(MRSA)treatment drugs in artificial joint infections from multiple perspectives and to solve the problem of MRSA infections in artificial joints.Methods Through literature research,relevant literature was retrieved and clinical studies meeting the requirements were selected and summarized.The Analytic Hierarchy Process(AHP)was applied to collect comprehensive clinical evaluation evidence and to conduct evaluations across different dimensions according to evaluation guidelines;the Delphi method combined with AHP was used for expert anonymous questionnaire evaluation,and the data was compared and analyzed.Results A clini-cal comprehensive evaluation index model for the treatment of artificial joint infections was successfully established,and the yaahp analysis software was used to score the comprehensive clinical evaluation evidence in various directions.Treatment drugs,vancomy-cin,daptomycin,and linezolid,at various levels were calculated through the software,and it was concluded that linezolid has the highest clinical comprehensive evaluation score.Conclusion Among the treatment drugs for MRSA infections in artificial joints,linezolid has a higher clinical comprehensive value and can provide a reference for the clinical treatment of MRSA infec-tions in artificial joints.