ObjectiveTo investigate the potential targets of 2，5-dihydroxybenzoic acid （2，5-DHBA） in the treatment of metabolic dysfunction-associated fatty liver disease （MAFLD） and the molecular mechanism by which it regulates the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. MethodsA network pharmacology analysis was performed at first， and related databases were used to obtain the common action targets of 2，5-DHBA and MAFLD， followed by molecular docking and pathway enrichment analysis to predict the potential biological processes and signaling pathways regulated by these targets. Then mouse normal hepatocytes AML-12 were used for cell experiments， and CCK-8 assay was used to determine the three optimal intervention concentrations of 2，5-DHBA. AML-12 cells were divided into control group， model group （cells cultured in a medium containing 2 mmol/L free fatty acid ［FFA］ to establish a cell model of MAFLD）， and three 2，5-DHBA intervention groups （cells cultured with FFA and 2，5-DHBA at the three different concentrations of 1.25， 5， and 20 μmol/L， respectively）. Oil red O staining was used to observe intracellular lipid accumulation； the fluorescent probe DCFH-DA was used to measure the level of intracellular reactive oxygen species （ROS）； biochemical assays were used to measure the content of triglyceride （TG） and total cholesterol （TC）； quantitative real-time PCR and Western Blot were used to measure the expression levels of related genes and proteins. A one-way analysis of variance was used for comparison between multiple groups， and the Tukey’s test was used for further comparison between two groups. ResultsA total of 32 common targets were obtained for 2，5-DHBA and MAFLD. Within a concentration range of 1.25 — 20 μmol/L， 2，5-DHBA treatment， starting from the concentration of 2.5 μmol/L， increased the viability of AML-12 cells in a dose-dependent manner. The minimum effective concentration of 1.25 μmol/L， the intermediate gradient concentration of 5 μmol/L， and the maximum safe concentration within the effective range of 20 μmol/L were selected for low-， middle-， and high-dose intervention， respectively. Compared with the model group， 2，5-DHBA intervention at concentrations of 1.25， 5， and 20 μmol/L could significantly reduce lipid droplet accumulation in cells （all P<0.05）， and there were significant differences in TG and TC between the model group and the three intervention groups （all P<0.05）. Compared with the control group， the model group had a significant increase in ROS fluorescence intensity （P<0.05）， and compared with the model group， there was a dose-dependent reduction in intracellular ROS level after treatment with 5 μmol/L or 20 μmol/L 2，5-DHBA （P<0.05）. Compared with the model group， 2，5-DHBA treatment at concentrations of 5 and 20 μmol/L significantly downregulated the mRNA expression levels of the lipogenic genes SREBf1 and FASN and upregulated the mRNA expression levels of the key antioxidant gene Nrf2 and its downstream target gene HO-1 （all P<0.05）. Compared with the control group， the expression of p-PI3K/PI3K and p-Akt/Akt in the model group was significantly increased （all P<0.05）. Compared with the model group， the protein expression levels of p-PI3K/PI3K and p-Akt/Akt were significantly decreased after 5 μmol/L 2，5-DHBA treatment （P<0.05）. Compared with the control group， the expression levels of Nrf2 and HO-1 protein in the model group were significantly decreased （all P<0.05）. The protein levels of Nrf2 and HO-1 were significantly increased after treatment with 1.25 μmol/L 2，5-DHBA （P<0.05）. ConclusionNetwork pharmacology and cellular experiments confirm that 2，5-DHBA can alleviate lipid deposition and oxidative stress by regulating the PI3K/Akt signaling pathway， thereby exerting a therapeutic effect on MAFLD.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease lacking effective therapy. Metformin, an antidiabetic medication, has shown promising therapeutic properties in preclinical fibrosis models; however, its precise cellular targets and associated mechanisms in fibrosis resolution remain incompletely defined. Most research on metformin's effects has focused on mesenchymal and inflammatory responses with limited attention to epithelial cells. In this study, we utilized Sftpc lineage-traced and Fgfr2b conditional knockout mice, along with BMP2/PPARγ and AMPK inhibitors, to explore metformin's impact on alveolar epithelial cells in a bleomycin-induced pulmonary fibrosis model and cell culture. We found that metformin increased the proliferation and differentiation of alveolar type 2 (AT2) cells, particularly the recently identified injury-activated alveolar progenitors (IAAPs)-a subpopulation characterized by low SFTPC expression but enriched for PD-L1. Single-cell RNA sequencing revealed a reduction in apoptosis among mature AT2 cells. Interestingly, metformin's therapeutic effects were not significantly affected by BMP2 or PPARγ inhibition, which blocked the lipogenic differentiation of myofibroblasts. However, Fgfr2b deletion in Sftpc lineage cells significantly impaired metformin's ability to promote fibrosis resolution, a process linked to AMPK signaling. In conclusion, metformin alleviates fibrosis by directly activating AT2 cells, especially the IAAPs, through a mechanism that involves AMPK and FGFR2b signaling, but is largely independent of BMP2/PPARγ pathways.

Objective To explore the effect of exenatide on oxidative stress in the hypothalamus of diabetes mice and its potential mechanism.Methods After one week of adaptive feeding,C57BL/6J mice were randomly divided into the CON group(normal chaw diet),the T2DM group(high-fat diet,HFD),and the T2DM+Exe group(HFD+exenatide).After 8 weeks of HFD,mice in the T2DM+Exe group were intraperitoneally injected with exenatide[24 nmol/(kg·d)]for 8 weeks.The weight and glucose and lipid metabolism levels of the mice were measured,and the levels of inflammatory and adipokine factors in mice were detected using the ELISA method.Western Blot was used to detect the expression of melanocortin receptor-4(MC4R)and proopiomelanocor-tin(POMC)in the hypothalamus.Hypothalamic mitochondria were extracted,and the content of mitochondrial reactive oxygen species(ROS)was measured using a flow cytometer.The content of malondialdehyde(MDA)and the activities of superoxide dismutase(SOD)in the mitochondria were detected using assay kits.Changes in the ultrastructure of mitochondria were observed using a transmission electron microscope.In vitro experiments,pal-mitic acid(PA)and exenatide were used to treat hypothalamic GT1-7 cells,and short hairpin RNA(shRNA)was used to silence the melanocortin 4 receptor(MC4R),and observe the cellular oxidative stress and lipid deposition.Results Compared with the CON group,the T2DM group mice showed a significant increase in glucose and lipid metabolism indicators,pro-inflammatory factors,and adipose factor levels(P<0.05),the expression of MC4R and POMC proteins in the hypothalamus were decreased(P<0.05),and the mitochondrial ROS and MDA content in the hypothalamus significantly were increased(P<0.05),while SOD and CAT activities were decreased(P<0.05).Mitochondrial morphology was abnormal.After intervention with exenatide,the above indicators were signifi-cantly improved.After inhibiting MC4R expression in vitro experiments,compared with the intervention group with exenatide,the ROS and MDA content was significantly increased(P<0.05),SOD activity was decreased(P<0.05),and lipid deposition occurred in the cells.Conclusions Exenatide exhibits a protective effect on hypotha-lamic oxidative stress injury in diabetic mice,and this mechanism may be associated with the upregulation of MC4R expression.

Objective To systematically review the application and effectiveness of deep learning(DL)in diagnosis of mild cogni-tive impairment(MCI)among older adults.Methods PubMed,Web of Science,CNKI and Wanfang databases were searched for literatures related to the application of DL in MCI among older adults,from database inception to December,2024.A scoping review was conducted.The literature screening process followed the Scoping Review Report Specification list,and the quality assess-ment was conducted using the cross-sectional study quality evaluation tool developed by the Evidence-based Health Care Center.Results A total of eleven papers were included,from Italy,USA,South Korea,China,India and Switzerland,involving 11 829 elderly participants,publicated mainly between 2014 and 2024,reflecting the rapid development trend of the field in the last decade,which was in line with the timing of the development of DL technology.The quality scores of the included literatures were all six to seven.The types of studies were all cross-sectional studies with significant cross-disciplinary characteristics,mainly originating from the fields of clinical medicine,biology and neuroimaging.The literature data were mainly based on the Alzheimer's disease Neuroimaging Program database and integrated other data resources.In terms of data type,in addition to brain imaging data,one study based on text data was also included.In terms of models used,five of the studies were mainly based on convolutional neu-ral networks,and the rest used different DL modeling frameworks.The task types contained binary and triple classification.In terms of prediction results,the DL models constructed on multimodal data,such as brain imag-es,could be used to construct high-precision prediction models for MCI classification,and the models were all good,with accuracy more than 70%and AUC values more than 0.7.The diagnostic accuracy of some of the mod-els was more than 90%,and the model with the highest prediction accuracy was the one that used the Biceph-Net lightweight framework,with accuracy close to 100%,and the text analysis model based on Transformer made the AUC value of 0.846,which provided new ideas for the diagnosis of non-imaging data.Conclusion DL can not only provide strong support for the accurate identification of MCI in the elderly,but also provide auxiliary prediction tools for clinicians,which can help delay the progression of the disease and improve the prognosis of patients.

Objective To establish an ICU nursing shift handover index based on the standardised communication framework of ISBAR(Identity,Situation,Background,Assessment,and Recommendation)and create an intelligent nursing shift handover system(hereinafter referred as"Smart ICU-ISBAR Nursing Shift Handover System"),thereby improving the standardisation,efficiency and quality of ICU nursing shift handovers with a standardised tool for planning ICU nursing shift handovers.Methods Literature was searched to identify the core elements of ISBAR and the key contents of ICU nursing shift handovers,then a preliminary draft of ICU nursing shift handover index was proposed.Delphi expert-consensus technique(20 experts)was used to screen and finalise the core dimensions and specific indicators of the index system,which were then integrated into the Smart ICU-ISBAR Nursing Handover System.Finally,the clinical effectiveness of the system was evaluated.Results Both Delphi rounds achieved 100.00%response rate.The expert authority coefficient was 0.83.The Kendall's W values of 2 rounds were 0.127 and 0.166(all P<0.001)respectively.The index importance scores ranged from 4.25-4.95 and 3.90-5.00,with coefficients of variation of 0.05-0.19 and 0.00-0.22,respectively.The final version of Smart ICU-ISBAR nursing shift handover system comprised 6 primary indicators and 60 secondary indicators.Over the clinical trials,the system achieved a 96.67%success rate in data-upload with an average response time of 1.80 sec.,the mean documentation time of shift handover at(1.97±0.58)min per patient,12 nurses'satisfaction with the shift handover quality of(4.47±0.25)and the rating of the system's usability of(4.75±0.08).The system was highly practical,convenient and intelligent.Conclusion The ICU nursing shift handover index system developed on the basis of ISBAR theory features a structural integrity,standardisation and ICU-specific characteristics and it is objective,scientific and rigorous.The Smart ICU-ISBAR Nursing Shift Handover System standardises the shift handover process,reduces information omissions,and improves efficiency and quality of nursing shift handover process.It serves as a standardised shift handover tool for ICU nursing shifts.

Objective To establish an ICU nursing shift handover index based on the standardised communication framework of ISBAR(Identity,Situation,Background,Assessment,and Recommendation)and create an intelligent nursing shift handover system(hereinafter referred as"Smart ICU-ISBAR Nursing Shift Handover System"),thereby improving the standardisation,efficiency and quality of ICU nursing shift handovers with a standardised tool for planning ICU nursing shift handovers.Methods Literature was searched to identify the core elements of ISBAR and the key contents of ICU nursing shift handovers,then a preliminary draft of ICU nursing shift handover index was proposed.Delphi expert-consensus technique(20 experts)was used to screen and finalise the core dimensions and specific indicators of the index system,which were then integrated into the Smart ICU-ISBAR Nursing Handover System.Finally,the clinical effectiveness of the system was evaluated.Results Both Delphi rounds achieved 100.00%response rate.The expert authority coefficient was 0.83.The Kendall's W values of 2 rounds were 0.127 and 0.166(all P<0.001)respectively.The index importance scores ranged from 4.25-4.95 and 3.90-5.00,with coefficients of variation of 0.05-0.19 and 0.00-0.22,respectively.The final version of Smart ICU-ISBAR nursing shift handover system comprised 6 primary indicators and 60 secondary indicators.Over the clinical trials,the system achieved a 96.67%success rate in data-upload with an average response time of 1.80 sec.,the mean documentation time of shift handover at(1.97±0.58)min per patient,12 nurses'satisfaction with the shift handover quality of(4.47±0.25)and the rating of the system's usability of(4.75±0.08).The system was highly practical,convenient and intelligent.Conclusion The ICU nursing shift handover index system developed on the basis of ISBAR theory features a structural integrity,standardisation and ICU-specific characteristics and it is objective,scientific and rigorous.The Smart ICU-ISBAR Nursing Shift Handover System standardises the shift handover process,reduces information omissions,and improves efficiency and quality of nursing shift handover process.It serves as a standardised shift handover tool for ICU nursing shifts.

Objectives:To preliminarily investigate the safety and efficacy of same-day discharge(SDD)following radiofrequency catheter ablation for arrhythmia.Methods:A total of 50 consecutive patients who underwent radiofrequency catheter ablation for arrhythmia in the SDD strategy at Fuwai Hospital from 8 July 2024 to 18 September 2024 were included in this analysis.The study evaluated the immediate success rate of the ablation,the rate of all-cause and arrhythmia-related readmission,outpatient or emergency visits and incidence of complications within 30 days post ablation,and recurrence rate of arrhythmias over a 3-month follow-up period.Results:The average age of the 50 patients was(47.2±16.1)years old,32 patients(64.0%)were male.Radiofrequency catheter ablation was performed in 47 patients(94.0%),including 18(36.0%)atrial fibrillation(AF)ablation.Three patients(6.0%)underwent electrophysiological study only.The immediate success rate for ablation patients was 100%(47/47).None of the patients developed vascular puncture-related or ablation-related complications.The average hospital stay and postoperative observation time were(6.84±1.13)hours and(3.40±1.12)hours,respectively.The all-cause and arrhythmia-related readmission,outpatient or emergency visits rates within 30 days were 12.0%(6/50)and 2.0%(1/50),respectively.Two patients(4.0%)post ablation experienced AF recurrence during the 3-months follow-up period.Conclusions:Radiofrequency catheter ablation for arrhythmias in SDD strategy is safe,effective,and feasible.

Objectives:To preliminarily investigate the safety and efficacy of same-day discharge(SDD)following radiofrequency catheter ablation for arrhythmia.Methods:A total of 50 consecutive patients who underwent radiofrequency catheter ablation for arrhythmia in the SDD strategy at Fuwai Hospital from 8 July 2024 to 18 September 2024 were included in this analysis.The study evaluated the immediate success rate of the ablation,the rate of all-cause and arrhythmia-related readmission,outpatient or emergency visits and incidence of complications within 30 days post ablation,and recurrence rate of arrhythmias over a 3-month follow-up period.Results:The average age of the 50 patients was(47.2±16.1)years old,32 patients(64.0%)were male.Radiofrequency catheter ablation was performed in 47 patients(94.0%),including 18(36.0%)atrial fibrillation(AF)ablation.Three patients(6.0%)underwent electrophysiological study only.The immediate success rate for ablation patients was 100%(47/47).None of the patients developed vascular puncture-related or ablation-related complications.The average hospital stay and postoperative observation time were(6.84±1.13)hours and(3.40±1.12)hours,respectively.The all-cause and arrhythmia-related readmission,outpatient or emergency visits rates within 30 days were 12.0%(6/50)and 2.0%(1/50),respectively.Two patients(4.0%)post ablation experienced AF recurrence during the 3-months follow-up period.Conclusions:Radiofrequency catheter ablation for arrhythmias in SDD strategy is safe,effective,and feasible.

Objective To explore the effect of exenatide on oxidative stress in the hypothalamus of diabetes mice and its potential mechanism.Methods After one week of adaptive feeding,C57BL/6J mice were randomly divided into the CON group(normal chaw diet),the T2DM group(high-fat diet,HFD),and the T2DM+Exe group(HFD+exenatide).After 8 weeks of HFD,mice in the T2DM+Exe group were intraperitoneally injected with exenatide[24 nmol/(kg·d)]for 8 weeks.The weight and glucose and lipid metabolism levels of the mice were measured,and the levels of inflammatory and adipokine factors in mice were detected using the ELISA method.Western Blot was used to detect the expression of melanocortin receptor-4(MC4R)and proopiomelanocor-tin(POMC)in the hypothalamus.Hypothalamic mitochondria were extracted,and the content of mitochondrial reactive oxygen species(ROS)was measured using a flow cytometer.The content of malondialdehyde(MDA)and the activities of superoxide dismutase(SOD)in the mitochondria were detected using assay kits.Changes in the ultrastructure of mitochondria were observed using a transmission electron microscope.In vitro experiments,pal-mitic acid(PA)and exenatide were used to treat hypothalamic GT1-7 cells,and short hairpin RNA(shRNA)was used to silence the melanocortin 4 receptor(MC4R),and observe the cellular oxidative stress and lipid deposition.Results Compared with the CON group,the T2DM group mice showed a significant increase in glucose and lipid metabolism indicators,pro-inflammatory factors,and adipose factor levels(P<0.05),the expression of MC4R and POMC proteins in the hypothalamus were decreased(P<0.05),and the mitochondrial ROS and MDA content in the hypothalamus significantly were increased(P<0.05),while SOD and CAT activities were decreased(P<0.05).Mitochondrial morphology was abnormal.After intervention with exenatide,the above indicators were signifi-cantly improved.After inhibiting MC4R expression in vitro experiments,compared with the intervention group with exenatide,the ROS and MDA content was significantly increased(P<0.05),SOD activity was decreased(P<0.05),and lipid deposition occurred in the cells.Conclusions Exenatide exhibits a protective effect on hypotha-lamic oxidative stress injury in diabetic mice,and this mechanism may be associated with the upregulation of MC4R expression.

Objective To systematically review the application and effectiveness of deep learning(DL)in diagnosis of mild cogni-tive impairment(MCI)among older adults.Methods PubMed,Web of Science,CNKI and Wanfang databases were searched for literatures related to the application of DL in MCI among older adults,from database inception to December,2024.A scoping review was conducted.The literature screening process followed the Scoping Review Report Specification list,and the quality assess-ment was conducted using the cross-sectional study quality evaluation tool developed by the Evidence-based Health Care Center.Results A total of eleven papers were included,from Italy,USA,South Korea,China,India and Switzerland,involving 11 829 elderly participants,publicated mainly between 2014 and 2024,reflecting the rapid development trend of the field in the last decade,which was in line with the timing of the development of DL technology.The quality scores of the included literatures were all six to seven.The types of studies were all cross-sectional studies with significant cross-disciplinary characteristics,mainly originating from the fields of clinical medicine,biology and neuroimaging.The literature data were mainly based on the Alzheimer's disease Neuroimaging Program database and integrated other data resources.In terms of data type,in addition to brain imaging data,one study based on text data was also included.In terms of models used,five of the studies were mainly based on convolutional neu-ral networks,and the rest used different DL modeling frameworks.The task types contained binary and triple classification.In terms of prediction results,the DL models constructed on multimodal data,such as brain imag-es,could be used to construct high-precision prediction models for MCI classification,and the models were all good,with accuracy more than 70%and AUC values more than 0.7.The diagnostic accuracy of some of the mod-els was more than 90%,and the model with the highest prediction accuracy was the one that used the Biceph-Net lightweight framework,with accuracy close to 100%,and the text analysis model based on Transformer made the AUC value of 0.846,which provided new ideas for the diagnosis of non-imaging data.Conclusion DL can not only provide strong support for the accurate identification of MCI in the elderly,but also provide auxiliary prediction tools for clinicians,which can help delay the progression of the disease and improve the prognosis of patients.