Aim To explore the potential mechanism of metformin on ATP-binding cassette transport A1(ABCA1)expression.Methods J774A.1 macrophages were treated with metformin and cycloheximide,and ABCA1 expression was determined by Western blot.His-tagged ABCA1 and HA-tagged Ub plasmids were co-transferred into HEK293 cells and stimulated with metformin.Co-immunoprecipitation(Co-IP)was used to test the binding ability of ABCA1 and ubiquitin.Candidate E3 ubiquitin-protein ligases(CE3)of ABCA1 were identified through Co-IP-based pro-teomics.The MIB1 plasmid was constructed and transferred into HEK293 cells,and Western blot was used to determine the effect of metformin and MIB1 on ABCA1 expression.Results Metformin increased the expression of ABCA1 in J774A.1 cells(P<0.01),and inhibited ABCA1 degradation(P<0.05).Metformin disrupted the binding of ABCA1 to ubiquitin(P<0.05).The proteins regulated by metformin in ABCA1 expression were primarily enriched in pathways re-lated to cell development,inflammation and immune defense.Metformin may upregulate ABCA1 protein expression via MIB1(P<0.05).Conclusion Metformin inhibits the degradation of ABCA1 by blocking the ubiquitin-proteasome system(UPS),and MIB1 might act as a candidate E3 ubiquitin-protein ligase(CE3)for ABCA1.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.

Objective:To analyze the current status and influencing factors of balance ability in elderly inpatients, and to explore the correlation between balance function and the tendency to suffer from geriatric syndromes.Methods:A total of 262 elderly patients hospitalized from April to August 2023 were selected as the research objects by convenience sampling method.A systematic health assessment was performed by professional evaluators using the "Edge Intelligent Geriatric Assessment System" software of the Jiangsu Province Hospital within one week after admission.According to the results of Performance Oriented Mobility Assessment(POMA), the subjects were divided into normal balance group(n=188), POMA score 19 to 24 group(n=36)and less than 19 score group(n=38), the differences in the tendency of the three groups of patients to develop geriatric syndromes were compared.Logistic regression analysis was used to screen the related factors and construct the regression equation.Receiver operating characteristic(ROC)curve was drawn to evaluate the predictive value of regression equation.Results:A total of 262 patients, of which 156(59.54%)were males, with an age range of 60 to 100 years(mean age 74.11±8.77 years)were included in the study.The total POMA score of 262 patients was 23.69±6.00, of which 74 cases(28.24%)had balance dysfunction.Univariate analysis showed that there were significant differences in age( t=20.356, P<0.001), serum albumin( t=3.999, P=0.019), proportions of people suffering from depression, frailty, sarcopenia, sleep disorders, nutrition risk and high fall risk between patients with different balance ability( χ2=10.250, 76.763, 101.728, 37.805, 22.472, 75.095, all P<0.05).Binary logistic regression model showed that age, sarcopenia, suspected insomnia, insomnia, and nutritional risk were independent predictors of balance ability in elderly patients(OR=1.071, 12.424, 6.719, 8.321, 3.440, all P<0.05).The above related variables were included in the regression equation: Logit(P)=-8.792+ 0.069×age+ 2.520×sarcopenia+ 1.905×suspected insomnia+ 2.119×insomnia+ 1.236×nutritional risk.ROC curve analysis showed that the area under the curve(AUC)was 0.902(95% CI: 0.857-0.946, P<0.001), the predictive specificity was 86.17% and the sensitivity was 85.14%. Conclusions:Age≥75.5 years, sarcopenia, sleep disorders, and nutritional risk could be used as predictors of balance disorders in elderly inpatients.The regression model constructed based on these indicators has a good predictive value.The establishment of the edge intelligent geriatric assessment system promotes the improvement of medical information level.

Objective:To evaluate the efficacy and safety of regional citrate anticoagulation (RCA) during plasma exchange (PE) in pediatric patients.Methods:We conducted a retrospective analysis of 12 critically ill children admitted to the Pediatric Intensive Care Unit (PICU) of Jinan Children's Hospital, who underwent 28 PE sessions with RCA between December 2023 and August 2024. Clinical records were reviewed to assess bleeding events, extracorporeal circuit performance, and changes in arterial blood gas parameters, serum total calcium (Ca tot), and activated clotting time before and after treatment. Results:No patients exhibited signs of increased bleeding. In one case, the procedure was discontinued prematurely due to elevated venous pressure. A significant decrease in ionized calcium (Ca ion) was observed 0.5 hours post-treatment. At the end of PE, pH, HCO 3?, base excess (BE), lactate, PaCO 2, Ca tot, and Na + levels increased, while K + and Ca ion levels decreased, with all changes being statistically significant. Four hours post-treatment, pH, HCO 3?, BE, PaCO 2, and Na + remained elevated, whereas Ca ion, lactate, and K + returned to baseline. By 12–15 hours post-treatment, all parameters—including pH, HCO 3?, BE, PaCO 2, Na +, K +, Ca ion, and lactate—had normalized, showing no significant differences from pre-treatment levels. Conclusions:RCA provides effective extracorporeal anticoagulation during pediatric PE without increasing bleeding risk. However, metabolic complications—primarily metabolic alkalosis—are common. These disturbances typically resolve spontaneously and do not lead to severe adverse events. While no ideal anticoagulant for PE has yet been established, RCA remains a safe and effective option, particularly for pediatric patients at higher risk of bleeding.

Aim To explore the potential mechanism of metformin on ATP-binding cassette transport A1(ABCA1)expression.Methods J774A.1 macrophages were treated with metformin and cycloheximide,and ABCA1 expression was determined by Western blot.His-tagged ABCA1 and HA-tagged Ub plasmids were co-transferred into HEK293 cells and stimulated with metformin.Co-immunoprecipitation(Co-IP)was used to test the binding ability of ABCA1 and ubiquitin.Candidate E3 ubiquitin-protein ligases(CE3)of ABCA1 were identified through Co-IP-based pro-teomics.The MIB1 plasmid was constructed and transferred into HEK293 cells,and Western blot was used to determine the effect of metformin and MIB1 on ABCA1 expression.Results Metformin increased the expression of ABCA1 in J774A.1 cells(P<0.01),and inhibited ABCA1 degradation(P<0.05).Metformin disrupted the binding of ABCA1 to ubiquitin(P<0.05).The proteins regulated by metformin in ABCA1 expression were primarily enriched in pathways re-lated to cell development,inflammation and immune defense.Metformin may upregulate ABCA1 protein expression via MIB1(P<0.05).Conclusion Metformin inhibits the degradation of ABCA1 by blocking the ubiquitin-proteasome system(UPS),and MIB1 might act as a candidate E3 ubiquitin-protein ligase(CE3)for ABCA1.

Objective:To preliminarily investigate the safety and efficacy of programmed death-1(PD-1)inhibitor combined with cord blood-derived natural killer cells(NK cells)in the treatment of advanced malignant solid tumors in an exploratory clinical trial.Methods:Three patients with advanced solid tumors treated at the Second Affiliated Hospital of Xi'an Medical University from December 2019 to December 2021 were enrolled.According to tumor type and CSCO guidelines,patients received multiple treatment cycles(21 days per cycle)consisting of standard chemotherapy,targeted therapy,or bevacizumab combined with PD-1 inhibitor.Umbilical cord blood-derived NK cells(8×107 cells per infusion)were infused at appropriate intervals during the treatment course.Target lesion size,tumor markers,levels of 12 peripheral blood cytokines,and lymphocyte subsets were assessed in each treatment cycle.Adverse events were also monitored throughout the treatment.Results:Following the treatment with PD-1 inhibitor combined with cord blood NK cells,2 patients achieved stable disease(SD,per RECIST 1.1 criteria),with durations of 118 days and 92 days,respectively.After NK cell infusion,patient#1 exhibited a marked decrease in the tumor marker CA199 to normal range and sustained for three follow-up periods;patient#2 showed significant reductions in tumor markers CA199,CA242,and CA724.Conclusion:The combination of NK cells with chemotherapy and PD-1 inhibitor demonstrates potential therapeutic efficacy for solid tumors.No severe immune-related adverse reactions were observed in the three patients enrolled in this study.

Objective To investigate alterations in interhemispheric functional connectivity(FC)in the cerebral cortices connected via the corpus callosum in patients with Alzheimer's disease(AD),and to explore their relationships with cognitive function and activities of daily living.Methods Resting-state functional magnetic resonance imaging data were collected from 28 patients with Alzheimer's dementia(d-AD),47 patients with mild cognitive impairment(MCI),and 37 healthy controls(HC).Using a trancallosal tract template,32 pairs of homologous cortical brain regions directly connected to 32 subregions of the corpus callosum were selected as regions of interest for interhemispheric FC analysis.Further correlation analyses were performed between FC values in patient groups and their scores on the Montreal Cognitive Assessment-Basic(MoCA-B)Scale and the Activities of Daily Living(ADL)Scale.Results Compared with HC group,both MCI and d-AD groups exhibited hyperconnectivity(significantly increased FC)in interhemispheric non-homologous brain regions.Specifically,hyperconnectivity in the MCI group was scattered across the frontal,parietal,temporal,and occipital lobes,while in the d-AD group,it was concentrated within the precentral and postcentral gyri.Notably,hyperconnectivity involving the prefrontal and occipital lobes in the MCI group showed significant declines in the d-AD group.The interhemispheric homologous FC in the d-AD group reduced more significantly than the MCI group.Additionally,in the d-AD group,2 interhemispheric FC within the prefrontal lobe(between the bilateral orbital parts of the inferior frontal gyrus,and between the left medial frontal gyrus and the right middle frontal gyrus)were correlated with MoCA-B scores,and 2 FC(between the bilateral middle occipital gyri,and between the left inferior parietal lobule and the right middle frontal gyrus)were correlated with ADL scores.Conclusion MCI and d-AD exhibit distinct patterns of interhemispheric FC alterations,and the interhemispheric FC changes in AD patients are non-progressive.The close relationships between interhemispheric homologous/non-homologous FC and MoCA-B/ADL scores in d-AD patients provide an objective basis and reference for clinical neuromodulation.

Objective To explore function-structure covariant patterns in Alzheimer's disease(AD)and mild cognitive impairment(MCI),and to investigate their associations with cognitive function and activities of daily living.Methods three-way parallel group independent component analysis(three-way pGICA),was used to identify the covariant patterns of resting-state functional MRI temporal data,gray matter density maps,and fractional anisotropy(FA)maps,and the differences between different groups were compared.Furthermore,the associations of covariant patterns with the Montreal Cognitive Assessment-Basic(MoCA_B)Scale scores and Activities of Daily Living Scale scores were analyzed.Results The function-structure covariant patterns in AD and MCI were characterized by the enhanced negative functional connectivity between the left posterior salience network and the right default mode network,the decreased gray matter density in the bilateral dorsolateral prefrontal cortex,and the reduced FA values in the left superior corona radiata(correlations:P<0.001,FDR corrected).Compared with HC group,AD group showed significant abnormalities in all identified covariant patterns(P<0.01,FDR corrected),but MCI group only exhibited a significant decrease in gray matter density in the bilateral dorsolateral prefrontal cortex(P<0.05,FDR corrected).Additionally,AD group had significantly lower FA value in the left superior corona radiata than MCI group(P<0.05,FDR corrected).The loadings reflecting the degree of covariation were significantly correlated with the Activities of Daily Living Scale scores(P<0.05,FDR corrected)but not with MoCA_B Scale scores.Conclusion The function-structure covariant patterns in AD and MCI are consistent with the declines in activities of daily living.The multimodal fusion analysis(three-way pGICA)provides a novel approach to understand the brain damage mechanisms underlying the covariant evolution of MCI and AD.

Objective:To develop a Pain Management Nursing Competency Evaluation Index System for surgical nurses, providing a framework for assessing their pain management competency and guiding in-service training programs.Methods:From December 2023 to July 2024, a research team employed literature analysis, semi-structured interviews, expert consultations, and the analytic hierarchy process (AHP) to determine the content and weight of the competency evaluation index system. A cross-sectional survey was subsequently conducted using convenience sampling on 788 surgical nurses to test the internal consistency, test-retest reliability, and content validity of the index system.Results:The response rates for the two rounds of expert consultations were both 100% (46/46), with an expert authority coefficient of 0.921; the Kendall′s coefficients of expert opinions for the primary indicators were 0.106 and 0.245, respectively. The final index system included seven primary indicators (routine pain assessment, assessment and management of active and unexpected pain, pharmacological pain management, patient-controlled analgesia nursing, non-pharmacological pain management, pain related education for patients and their families, and professional development), 23 secondary indicators, and 78 tertiary indicators. The overall Cronbach α was 0.991, the test-retest reliability was 0.493, the item-level content validity index ranged from 0.96 to 1.00, and the scale-level content validity index was 0.98.Conclusions:The pain management nursing competency evaluation index system for surgical nurses is scientifically valid, reliable, and practical. It offers a solid foundation for evaluating the pain management competencies of surgical nurses and designing targeted in-service training programs.

Objective To explore function-structure covariant patterns in Alzheimer's disease(AD)and mild cognitive impairment(MCI),and to investigate their associations with cognitive function and activities of daily living.Methods three-way parallel group independent component analysis(three-way pGICA),was used to identify the covariant patterns of resting-state functional MRI temporal data,gray matter density maps,and fractional anisotropy(FA)maps,and the differences between different groups were compared.Furthermore,the associations of covariant patterns with the Montreal Cognitive Assessment-Basic(MoCA_B)Scale scores and Activities of Daily Living Scale scores were analyzed.Results The function-structure covariant patterns in AD and MCI were characterized by the enhanced negative functional connectivity between the left posterior salience network and the right default mode network,the decreased gray matter density in the bilateral dorsolateral prefrontal cortex,and the reduced FA values in the left superior corona radiata(correlations:P<0.001,FDR corrected).Compared with HC group,AD group showed significant abnormalities in all identified covariant patterns(P<0.01,FDR corrected),but MCI group only exhibited a significant decrease in gray matter density in the bilateral dorsolateral prefrontal cortex(P<0.05,FDR corrected).Additionally,AD group had significantly lower FA value in the left superior corona radiata than MCI group(P<0.05,FDR corrected).The loadings reflecting the degree of covariation were significantly correlated with the Activities of Daily Living Scale scores(P<0.05,FDR corrected)but not with MoCA_B Scale scores.Conclusion The function-structure covariant patterns in AD and MCI are consistent with the declines in activities of daily living.The multimodal fusion analysis(three-way pGICA)provides a novel approach to understand the brain damage mechanisms underlying the covariant evolution of MCI and AD.