Aldehyde oxidase (AOX) is a molybdoenzyme that is primarily expressed in the liver and is involved in the metabolism of drugs and other xenobiotics. AOX-mediated metabolism can result in unexpected outcomes, such as the production of toxic metabolites and high metabolic clearance, which can lead to the clinical failure of novel therapeutic agents. Computational models can assist medicinal chemists in rapidly evaluating the AOX metabolic risk of compounds during the early phases of drug discovery and provide valuable clues for manipulating AOX-mediated metabolism liability. In this study, we developed a novel graph neural network called AOMP for predicting AOX-mediated metabolism. AOMP integrated the tasks of metabolic substrate/non-substrate classification and metabolic site prediction, while utilizing transfer learning from ¹³C nuclear magnetic resonance data to enhance its performance on both tasks. AOMP significantly outperformed the benchmark methods in both cross-validation and external testing. Using AOMP, we systematically assessed the AOX-mediated metabolism of common fragments in kinase inhibitors and successfully identified four new scaffolds with AOX metabolism liability, which were validated through in vitro experiments. Furthermore, for the convenience of the community, we established the first online service for AOX metabolism prediction based on AOMP, which is freely available at https://aomp.alphama.com.cn.

Objective:To explore the cognition and use experience of residents based on technical acceptance model, and provide decision-making information and reference for the promotion and optimization construction of the smart ward.Methods:Based on the technical acceptance model, the research team made cognitive and experience evaluation questionnaire of hospitalization patients of the smart wards and evaluated its reliability. By adopting cross-sectional research methods, 368 patients who were hospitalized in the smart wards of the 10 leading clinical specialty in"136" Xingyi Project in Shanxi Province were selected as research objects from January to April 2022. The cognitive and experience evaluation questionnaire of hospitalization patients of the smart wards were used to conduct investigations and research.Results:Among 368 patients, male 148 cases, female 220 cases, aged 18 to 70 years old. The overall Cronbach α coefficient of the questionnaire was 0.887, which had a good degree of reliability. In the cognition and experience evaluation of the smart wards, the five dimensions of perception of usefulness, perception of ease of use, perception safety, attitude and willingness to use were (4.76 ± 0.38),(4.75 ± 0.46), (4.75 ± 0.46), (4.72 ± 0.19), (4.73 ± 0.55), (4.77 ± 0.27) points respectively, the proportion of "very agreed" was 80.16% (295/368); the overall satisfaction of the smart wards scored (4.76 ± 0.35) points, the proportion of "very satisfied" was 79.35% (292/368). Conclusions:The application of the smart ward in the nursing work of inpatients will help optimize the patients′ medical service experience and improve the satisfaction of hospitalization.

Objective:To investigate the serum metabolites and their metabolic characteristics of patients with optic neuritis.Methods:Case-control study. From January 2021 to January 2022, 9 serum specimens of diagnosed patients with optic neuritis were collected in Department of Neurology from Beijing Tongren Hospital and 9 healthy subjects as the control. Among them, there were 5 females and 4 males in the optic neuritis group, aged (35.8±12.9) years; there were 5 females and 4 males in the healthy control group, aged (32.6±8.6) years. Liquid chromatography-mass spectrometry was used to detect metabolites in serum of healthy control and patients with optic neuritis. The principal component analysis (PCA) and orthogonal partial least-squares discriminination analysis (OPLS-DA) were used to analyze the differential metabolites . The variable importance projection value of OPLS-DA model and the P value of t-test was applied to find the different metabolites. Results:Thirty-seven metabolites were finally identified from serum samples. Four metabolites with variable important in projection (VIP) values larger than 1 and P values less than 0.05 were teased out, three metabolites, LysoPC (P-16∶0), LysoPC (16∶0), LysoPC (P-18∶0) belonge to phospholipid and one metabolite was L-Threonine, they were all down-regulated. The area under curve were 0.951, 0.889, 0.963 and 0.944, respectively. Conclusion:Based on metabonomic analysis, some metabolites in serum have changed, which can provide basis for biomarkers screening of optic neuritis.

Objective To investigate the consistency analysis between multimodal MRI in determining vaginal involvement and parametrial infiltration in cervical cancer patients and pathological examination.Methods Ninety-two patients with cervical cancer were regressively selected and who underwent preoperative multimodal MRI examination.Using pathological results as the gold standard,the receiver operating characteristic(ROC)curve was used to analyze the diagnostic efficacy of conventional MRI,diffusion weighted imaging(DWI)and dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)alone and in combination in predic-ting vaginal involvement and parametrial infiltration.Results(1)Vaginal involvement:the diagnostic sensitivity of conventional MRI was 65.96％,the specificity was 91.11％,and the area under the curve(AUC)was 0.775[95％confidence interval(CI)0.676-0.873].The sensitivity of DCE-MRI was 61.70％,the specificity was 95.56％,and the AUC was 0.797(95％CI 0.702-0.892).The sensitivity of DWI was 72.34％,the specificity was 88.89％,and the AUC was 0.817(95％CI 0.725-0.908).At the optimal cut-off point,the sensitivity of parallel combined detection was 97.87％,the specificity was 93.33％,and the AUC was 0.956(95％CI 0.907-0.918).(2)Parametrial infiltration:the diagnostic sensitivity of conventional MRI was 67.24％,the specificity was 91.18％,and the AUC was 0.783(95％CI 0.688-0.879).The sensitivity of DCE-MRI was 62.07％,the specificity was 94.12％,and the AUC was 0.781(95％CI 0.686-0.875).The sensitivity of DWI was 75.86％,the specificity was 97.06％,and the AUC was 0.865(95％CI 0.788-0.941).At the optimal cut-off point,the sensitivity of parallel combined detection was 98.28％,the specificity was 91.18％,and the AUC was 0.947(95％CI 0.888-1.000).Conclusion Combined multimodal MRI can improve the positive detection rate of vaginal involve-ment and parametrial infiltration in patients with cervical cancer,allowing for timely treatment adjustments,improved quality of life and longer survival.

AIM:To determine the link between infliximab,adalimumab,vedolizumab,ustekinumab and risk of lymphoma in order to provide reference for the safety of clinical application.METHODS:Dis-proportionality analysis and Bayesian analysis were used in data mining to screen the suspected lym-phoma after the use of four biological agents based on the FAERS data from October 2012 to June 2023.The fatality and hospitalization rates of this four biological agents associated lymphoma were also investigated.RESULTS:Totally 705 cases of four biological agents associated lymphoma were collected.Four biological agents associated lymphoma appeared to influent more young pa-tients and middle-aged patients than elderly pa-tients(25.11％vs.22.41％vs.12.2％).There were slightly more male than females(42.84％vs.35.60％).Infliximab has the highest reporting odds ratio[ROR3.40,95％CI=(3.03,3.82)],proportional ratio[PRR3.38,95％CI=(3.01,3.79)],information component(IC1.14,IC-2SD=1.02)and empirical Bayes geometric mean(EBGM2.21,EBGM05=2.01).Significant difference in the fatality rate and hospi-talization rate among four biological agents were not found.CONCLUSION:Infliximab showed a strongest lymphoma association than the other three biological agents.Lymphoma risk should be vigilant when using infliximab.

AIM:To evaluate the efficacy,safety,and economy of camrelizumab(CAM)combined with platinum-containing chemotherapy(CT)for the first-line treatment of locally advanced/meta-static non-small cell lung cancer(NSCLC).METH-ODS:Chinese and English databases such as Pubmed,the Cochrane Library,China Knowledge Network,Wanfang Data,and other related web-sites were systematically searched.After literature screening,quality assessment,and data extraction of the literature according to the inclusion and ex-clusion criteria,two researchers conducted a rapid health technology assessment(HTA).RESULTS:A total of 7 systematic evaluations/Meta-analyses and 17 economics evaluations were included.In terms of effectiveness,compared to docetaxel che-motherapy,CAM+CT significantly prolonged the overall survival(OS),progression-free survival(PFS),and improved the objective remission rate(ORR)of mutation-negative patients with locally ad-vanced/metastatic NSCLC.Compared with CT and pembrolizumab(PEM),CAM+CT significantly pro-longed the PFS,and improved the ORR of mutation-negative patients with locally advanced/metastatic NSCLC.Subgroup analysis showed that CAM+CT significantly prolonged PFS in patients with PD-L1 ≥1％and PD-L1 ≥ 50％compared with CT.Compared with CT,CAM+CT significantly prolonged the OS and PFS of mutation-negative patients with locally advanced/metastatic squamous NSCLC.Compared with sintilimab(SIN),CAM+CT significantly pro-longed the PFS of mutation-negative patients with locally advanced/metastatic squamous NSCLC.Sub-group analysis showed that CAM+CT significantly prolonged OS in patients with PD-L1＜1％com-pared with CT.In terms of safety,CAM+CT was comparable in terms of the occurrence of all grades of adverse events,but the incidence of grade 3 or higher treatment-related adverse events was significantly increased compared with CT and PEM for mutation-negative locally advanced/meta-static NSCLC patients.CAM+CT was significantly in-creased the occurrence of all grades of adverse events compared with CT,but was comparable in terms of the occurrence of grade 3 or higher treat-ment-related adverse events.In terms of economy,CAM+CT has a cost-effectiveness advantage over CT for patients with mutation-negative advanced/metastatic squamous NSCLC.CAM+CT has a cost-effectiveness advantage over CT and PEM+CT;and CAM+CT does not have a cost-effectiveness ad-vantage over SIN+CT for patients with mutation-negative locally advanced/metastatic non-squa-mous NSCLC.CONCLUSION:CAM+CT has good ef-ficacy and cost-effectiveness for the first-line treat-ment of locally advanced/metastatic NSCLC,and the safety aspect is compared with CT,PEM or slightly worse.

Objective:To prepare recombinant protein of group 36 allergen of Dermatophagoides farinae(Der f 36),to deter-mine its immunogenicity and bioinformatics analysis was performed.Methods:Nucleic acid sequence coding for Der f 36 was obtained and artificially synthesized,pET-28a(+)was inserted to construct pET-28a(+)-Der f 36 plasmid and transformed into BL21(DE3)receptor cells.After expressed and purified in BL21(DE3),recombinant allergen rDer f 36 was obtained,recombinant protein rDer f 36 was identified by SDS-PAGE and Western blot.Serum IgE binding rates of rDer f 36 was determined by IgE-ELISA.Cross-reactivity between rDer f 36 and rDer p 36 was detected by IgE-ELISA inhibition assay.HNEpC cells were cultured with rDer f 36 for 24 h and cytokines were detected.Bioinformatics softwares were used to analyze physicochemical properties and structures of Der f 36 and Der p 36.Results:Coding gene for Der f 36 was obtained with a total length of 690 bp,whose molecular weight was 25.6 kD;serum IgE binding rate of rDer f 36 was 42.1%by IgE-ELISA;IgE-ELISA inhibition assay showed that rDer p 36 had 40%(8/20)inhibition rate(>50%)for rDer f 36,with an average inhibition rate of 52.98%.Compared with control group,HNEpC cells cultured with rDer f 36 showed that IL-6,IL-8,IL-33,IL-25 and TSLP expressions had increased;bioinformatics analyses show that sequence consistency of Der f 36 and Der p 36 was 77.63%,with similar physicochemical properties.Secondary structure analysis showed that both of them contained α helix,β-turn and random coils,and content of random coils was the highest;structure of C2 domains was also highly overlapping(RMSD=0.046).Conclusion:Recombinant allergen rDer f 36 is successfully prepared with good immunogenicity,laying foundation for diagnosis and treatment of dust mite allergen single component.High similarity in physical and chemical properties,secondary structure,and tertiary structure between Der f 36 and Der p 36 determines their cross reactivity.

Objective:To develop a risk assessment scale for infusion port occlusion in patients with malignant tumors and to test its reliability and validity.Methods:An initial item pool was constructed based on literature review. Through purposive sampling, two rounds of Delphi consultations with 20 experts were conducted from March to May 2023. Weights were assigned to the indicators using the analytic hierarchy process (AHP), and the risk assessment scale was finalized. From June to September 2023, a convenience sample of 278 malignant tumor patients with infusion ports from four Class Ⅲ Grade A hospitals in Shanxi Province was selected for item analysis and reliability and validity testing.Results:The risk assessment scale for infusion port occlusion in malignant tumor patients includes five dimensions, 16 primary indicators, and 35 secondary indicators. The content validity index at the scale level was 0.925, and at the item level ranged from 0.818 to 1.000. A total of five factors were extracted by exploratory factor analysis, with a cumulative contribution rate of 57.081% to the variance. The area under the receiver operating characteristic curve was 0.815, with a cutoff score of 24.50. The overall Cronbach's α coefficient was 0.910, and the split-half reliability coefficient was 0.762.Conclusions:The risk assessment scale for infusion port occlusion in malignant tumor patients demonstrates good reliability and validity, and has high predictive power, which provides a scientific basis for identifying high-risk populations in clinical settings.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective This study aims to investigate the application of symptom group management using a mo-bile health platform in managing heart failure patients during convalescence.Methods The research involved pa-tients with chronic heart failure who were treated at a tertiary A hospital in Qingdao from June 2022 to December 2022.The experimental group consisted of 235 patients who were discharged after treatment in ward A,while the control group consisted of 235 patients who were discharged during the same period in ward B.The experimental group received an mHealth-based symptom clusters management program following routine continuous nursing and the control group was given routine continuous nursing after discharge.6 months after the intervention,the heart function status,self-care level,and quality of life were compared between 2 groups.Results The experimental group ultimately included 232 cases,while the control group ultimately included 225 cases.Furthermore,the cardiac functional status,level of self-care,and quality of life of both the experimental group and the control group showed improvement compared to the pre-intervention period(P＜0.05).The experimental group exhibited significantly better cardiac function status compared to the control group,and the experimental group demonstrated higher levels of self-care confidence,and quality of life relative to the control group(P＜0.05).Conclusion The utilization of a mobile medical platform can enhance the management of heart failure patients'symptom groups,resulting in im-proved disease management efficiency.This platform provides patients with a comprehensive self-management plan,ultimately enhancing their self-management abilities and overall outcomes.