Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Objective To summarize and analyze the clinical and imaging features in patients with initial onset of anti-myelin oli-godendrocyte glycoprotein-IgG(MOG-IgG)associated disease(MOGAD).Methods The clinical and MRI data of 39 patients with serum MOG-IgG positive were analyzed retrospectively.Clinical features(including history of prior infection,initial symptoms and clinical phenotypes,cerebrospinal fluid examination,and serum antibody levels)and location,distribution,and enhancement patterns of lesions were all compared between adult and pediatric groups.Results Blurred vision was the most common initial symptom,with no statistically significant difference between the two groups.Compared to the adult group,the pediatric group more frequently presented with acute disseminated encephalomyelitis(ADEM)as the clinical phenotype.There were no statistically significant differ-ences between the two groups in cerebrospinal fluid examination results,including leukocyte count,protein content,and oligoclonal bands(OCB)positive.The pediatric group showed a higher prevalence of lesions in the cortical and subcortical white matter,deep white matter,and basal ganglia regions compared with the adult group.There was no statistically significant difference in the inci-dence of optic neuritis between the two groups.Spinal cord inflammation predominantly affected the cervical and thoracic segments,with central gray matter involvement presenting as the"H-sign".Conclusion The clinical and imaging features of MOGAD exhibit certain variations across different patient populations.Accurate recognition and early diagnosis of MOGAD and prompt examination and treatment are instrumental in improving patients'prognosis.

Objective To summarize and analyze the clinical and imaging features in patients with initial onset of anti-myelin oli-godendrocyte glycoprotein-IgG(MOG-IgG)associated disease(MOGAD).Methods The clinical and MRI data of 39 patients with serum MOG-IgG positive were analyzed retrospectively.Clinical features(including history of prior infection,initial symptoms and clinical phenotypes,cerebrospinal fluid examination,and serum antibody levels)and location,distribution,and enhancement patterns of lesions were all compared between adult and pediatric groups.Results Blurred vision was the most common initial symptom,with no statistically significant difference between the two groups.Compared to the adult group,the pediatric group more frequently presented with acute disseminated encephalomyelitis(ADEM)as the clinical phenotype.There were no statistically significant differ-ences between the two groups in cerebrospinal fluid examination results,including leukocyte count,protein content,and oligoclonal bands(OCB)positive.The pediatric group showed a higher prevalence of lesions in the cortical and subcortical white matter,deep white matter,and basal ganglia regions compared with the adult group.There was no statistically significant difference in the inci-dence of optic neuritis between the two groups.Spinal cord inflammation predominantly affected the cervical and thoracic segments,with central gray matter involvement presenting as the"H-sign".Conclusion The clinical and imaging features of MOGAD exhibit certain variations across different patient populations.Accurate recognition and early diagnosis of MOGAD and prompt examination and treatment are instrumental in improving patients'prognosis.

Objective:To screen risk factors for ICU-acquired weakness in patients with mechanical ventilation and construct a predictive model, so as to provide a basis for the health management of patients with mechanical ventilation.Methods:Convenience sampling was used to select 312 ICU patients with mechanical ventilation admitted to the Tenth People's Hospital of Tongji University from October 2019 to August 2020 for the study. Patients were divided into training set ( n=220) and test set ( n=92) in a 7∶3 ratio. Based on machine learning algorithms, decision random forest (DRF), extremely-randomized trees (XRT) and generalized linear model (GLM) were used to construct three ICU-acquired weakness risk prediction models for patients with mechanical ventilation, respectively. The performance of the prediction model was evaluated using the area under the receiver operating characteristic curve ( AUC), the area under the precision-recall curve ( AUPRC), and the root mean square error ( RMSE) . Results:There were 7 predictors of risk of ICU-acquired weakness in patients with mechanical ventilation, including age, gender, braking, duration of mechanical ventilation, blood glucose, lactic acid, and parenteral nutrition. Test set and training set validation showed that AUC and AUPRC of GLM prediction model were greater than those of DRF, XRT prediction model. Test set validation indicated that the RMSE, logarithmic loss of GLM prediction model was less than those of DRF, XRT prediction model. Conclusions:Machine learning algorithm based GLM prediction model has good prediction performance. Healthcare professionals can construct evidence-based decisions for interventions in areas such as braking, duration of mechanical ventilation, and blood glucose management.

Objective:To research on the application effect of the supply-processing-distribution (SPD) model based on risk perspective in the management of low-value medical consumables of clinical departments in hospital,so as to improve management efficiency of hospital for low-value medical consumables. Methods:Risk points in the management of low-value medical consumables were identified based on a risk perspective,and the SPD mode was adopted to conduct collaborative management for low-value medical consumables in the hospital. Low-value medical consumables were used in clinical departments of the Hospital of Chengdu University of Traditional Chinese Medicine from October 2021 to November 2023 were selected. According to random number table,885 medical consumables were used from October 2021 to October 2022 were managed by using the conventional management model,and another 885 medical consumables were used from November 2022 to November 2023 were managed by using the SPD model based on a risk perspective. The management effect scores,performance evaluation results,management efficiency,and incidence of adverse situations of low-value medical consumables were compared between the two management modes. Results:The average scores of occurring problems and operation cost of low-value medical consumables in the SPD model group were respectively (15.14±2.06) and (20.44±3.16),which were lower than those in the conventional management model group,with statistically significant differences (t=84.009,92.863,P<0.05). The average scores of delivery timeliness,work efficiency,standardization,traceability of consumables,waste recycling of consumables,delivery satisfaction,and demand forecasting were respectively (97.14±10.11),(95.25±10.85),(89.65±12.54),(88.25±9.14),(94.14±10.22),(88.14±9.22),and (95.84±10.33) in the SPD model group,which were higher than those in the conventional management model group,with statistically significant differences (t=78.169,77.874,75.326,68.557,35.288,25.422,102.959,P<0.05). The average issuance time and replenishment time of low-value medical consumables in the SPD model group were respectively (6.11±0.72) min and (12.58±2.35) h,which were shorter than those in the conventional management model group,with statistically significant differences (t=54.129,122.343,P<0.05). The issuance accuracy rate and proportion of saved amount of low-value medical consumables in the SPD model group were respectively 98.76％ and 3.16％,which were higher than those in the conventional management model group,with statistically significant differences (x2=159.178,5.618,P<0.05). The number of issuance error and the proportion of expired consumables,invalid consumables or damaged consumables in the SPD model group were respectively 1.24％ and 0.90％,which were lower than those in the conventional management model group,with statistically significant differences (x2=159.178,23.792,P<0.05). The average time consuming of daily and monthly of low-value medical consumables in the SPD model group were respectively (0.29±0.02) h and (1.14±0.25) h,which were shorter than those in the conventional management model group,and the average number of monthly inventory backlog and average circulation time in the SPD model group were respectively (33.19±4.25) and (26.14±3.18) d,which were lower than those in the conventional management model group,with statistically significant differences (t=412.428,122.343,114.555,39.848,P<0.05). The incidence rates of unregistered use,unskilled operation,failure to enter data into the computer,carelessness during shift handovers,and loss of consumables of low-value medical consumables in the SPD model group were respectively 6.21％,7.12％,2.03％,2.26％ and 1.92％,which were lower than those in the conventional management model group,with statistically significant differences (x2=28.882,15.225,22.824,12.683,16.893,P<0.05). Conclusion:The application of the SPD model based on a risk perspective in the management of low-value medical consumables in clinical departments of hospital can reduce operating costs of hospital,and increase procurement efficiency for them,and enhance the level of refined management for low-value medical consumables.

Objective:To research on the application effect of the supply-processing-distribution (SPD) model based on risk perspective in the management of low-value medical consumables of clinical departments in hospital,so as to improve management efficiency of hospital for low-value medical consumables. Methods:Risk points in the management of low-value medical consumables were identified based on a risk perspective,and the SPD mode was adopted to conduct collaborative management for low-value medical consumables in the hospital. Low-value medical consumables were used in clinical departments of the Hospital of Chengdu University of Traditional Chinese Medicine from October 2021 to November 2023 were selected. According to random number table,885 medical consumables were used from October 2021 to October 2022 were managed by using the conventional management model,and another 885 medical consumables were used from November 2022 to November 2023 were managed by using the SPD model based on a risk perspective. The management effect scores,performance evaluation results,management efficiency,and incidence of adverse situations of low-value medical consumables were compared between the two management modes. Results:The average scores of occurring problems and operation cost of low-value medical consumables in the SPD model group were respectively (15.14±2.06) and (20.44±3.16),which were lower than those in the conventional management model group,with statistically significant differences (t=84.009,92.863,P<0.05). The average scores of delivery timeliness,work efficiency,standardization,traceability of consumables,waste recycling of consumables,delivery satisfaction,and demand forecasting were respectively (97.14±10.11),(95.25±10.85),(89.65±12.54),(88.25±9.14),(94.14±10.22),(88.14±9.22),and (95.84±10.33) in the SPD model group,which were higher than those in the conventional management model group,with statistically significant differences (t=78.169,77.874,75.326,68.557,35.288,25.422,102.959,P<0.05). The average issuance time and replenishment time of low-value medical consumables in the SPD model group were respectively (6.11±0.72) min and (12.58±2.35) h,which were shorter than those in the conventional management model group,with statistically significant differences (t=54.129,122.343,P<0.05). The issuance accuracy rate and proportion of saved amount of low-value medical consumables in the SPD model group were respectively 98.76％ and 3.16％,which were higher than those in the conventional management model group,with statistically significant differences (x2=159.178,5.618,P<0.05). The number of issuance error and the proportion of expired consumables,invalid consumables or damaged consumables in the SPD model group were respectively 1.24％ and 0.90％,which were lower than those in the conventional management model group,with statistically significant differences (x2=159.178,23.792,P<0.05). The average time consuming of daily and monthly of low-value medical consumables in the SPD model group were respectively (0.29±0.02) h and (1.14±0.25) h,which were shorter than those in the conventional management model group,and the average number of monthly inventory backlog and average circulation time in the SPD model group were respectively (33.19±4.25) and (26.14±3.18) d,which were lower than those in the conventional management model group,with statistically significant differences (t=412.428,122.343,114.555,39.848,P<0.05). The incidence rates of unregistered use,unskilled operation,failure to enter data into the computer,carelessness during shift handovers,and loss of consumables of low-value medical consumables in the SPD model group were respectively 6.21％,7.12％,2.03％,2.26％ and 1.92％,which were lower than those in the conventional management model group,with statistically significant differences (x2=28.882,15.225,22.824,12.683,16.893,P<0.05). Conclusion:The application of the SPD model based on a risk perspective in the management of low-value medical consumables in clinical departments of hospital can reduce operating costs of hospital,and increase procurement efficiency for them,and enhance the level of refined management for low-value medical consumables.

Objective:To screen risk factors for ICU-acquired weakness in patients with mechanical ventilation and construct a predictive model, so as to provide a basis for the health management of patients with mechanical ventilation.Methods:Convenience sampling was used to select 312 ICU patients with mechanical ventilation admitted to the Tenth People's Hospital of Tongji University from October 2019 to August 2020 for the study. Patients were divided into training set ( n=220) and test set ( n=92) in a 7∶3 ratio. Based on machine learning algorithms, decision random forest (DRF), extremely-randomized trees (XRT) and generalized linear model (GLM) were used to construct three ICU-acquired weakness risk prediction models for patients with mechanical ventilation, respectively. The performance of the prediction model was evaluated using the area under the receiver operating characteristic curve ( AUC), the area under the precision-recall curve ( AUPRC), and the root mean square error ( RMSE) . Results:There were 7 predictors of risk of ICU-acquired weakness in patients with mechanical ventilation, including age, gender, braking, duration of mechanical ventilation, blood glucose, lactic acid, and parenteral nutrition. Test set and training set validation showed that AUC and AUPRC of GLM prediction model were greater than those of DRF, XRT prediction model. Test set validation indicated that the RMSE, logarithmic loss of GLM prediction model was less than those of DRF, XRT prediction model. Conclusions:Machine learning algorithm based GLM prediction model has good prediction performance. Healthcare professionals can construct evidence-based decisions for interventions in areas such as braking, duration of mechanical ventilation, and blood glucose management.

BACKGROUND:Previous studies showed that extracts of Sambucus adnata Wall.have the ability to promote the proliferation and differentiation of osteoblasts,fracture healing,anti-inflammatory and antioxidant effects,which can effectively alleviate the development of osteoarthritis.Vascular endothelial growth factor,on the other hand,is a biomarker for the evaluation of osteoarthritis severity. OBJECTIVE:To investigate the effect and mechanism of two extracts of Sambucus adnata Wall.(methanol extract SAW-ME and dichloromethane extract SAW-DCE)on angiogenesis in osteoarthritis. METHODS:(1)Rat models of osteoarthritis were established using anterior cruciate ligament transection and given SAW-ME and SAW-DCE.A sham group was set as a control.Immunohistochemistry and immunofluorescence were used to detect the changes of articular vascular endothelial growth factor A in joint tissue and vascular endothelial growth factor and"H"type blood vessels in serum of osteoarthritis rats.(2)Vascular endothelial cells EA.hy926 were used as the research object and intervened with SAW-ME and SAW-DCE.Cell proliferation was then detected by MTT assay.Vascular endothelial growth factor was used to induce EA.hy926 cells,and the model of angiogenesis was replicated.Cell scratch assay and tube formation assay were performed to study the role and mechanism.(3)EA.hy926 cells were used for transcriptome sequencing to analyze the characteristic changes of cell differential genes and related functions after SAW-DCE intervention. RESULTS AND CONCLUSION:(1)SAW-ME and SAW-DCE downregulated the expression of vascular endothelial growth factor A in the rat knee cartilage and reduced the formation of"H"type vessels in osteoarthritis rats.SAW-ME could significantly decrease the level of vascular endothelial growth factor in serum of osteoarthritis rats(P<0.05).SAW-DCE could also decrease the level of vascular endothelial growth factor in serum of osteoarthritis rats,but there was no significant change.(2)Both SAW-ME and SAW-DCE significantly inhibited vascular endothelial cell migration and tube formation,and downregulated the expression of Ang1 and Tie2 proteins.(3)Transcriptome sequencing analysis found that abnormal angiogenesis in osteoarthritis was related to the PI3K/AKT signaling pathway.(4)To conclude,SAW-ME and SAW-DCE can inhibit angiogenesis in the rat model of osteoarthritis,and the mechanism may be related to the Ang1/Tie2 and PI3K/AKT signaling pathways.

Objective:To investigate the current situation of occurrence of social isolation in maintenance hemodialysis patients and analyze its influencing factors, in order to provide a theoretical basis for the implementation of targeted interventions.Methods:The study was a cross-sectional study. A total of 315 dialysis patients in three hemodialysis centers in Xinjiang were selected by simple sampling method from October 2021 to March 2022, who were investigated using the general information questionnaire, Lubben-6 social network scale, International Physical Activity Questionnaire (sedentary behavior section), Patient Health Questionnaire 9-item scale (PHQ-9) and Frail Scale. Univariate analysis and binary Logistic regression analysis were used to explore the influencing factors affecting the social isolation of dialysis patients.Results:Social isolation was present in 28.89% (91/315) of maintenance hemodialysis patients, and binary Logistic regression analysis revealed that age (45-59 years old: OR=4.815, 95% CI 1.362-17.017;≥60 years old: OR=8.968, 95% CI 2.349-34.236), dialysis age ( OR=2.788, 95% CI 1.334-5.826), sedentary behavior ( OR=2.504, 95% CI 1.406-4.461), depression ( OR=2.095, 95% CI 1.179-3.722), and debilitation ( OR=2.043, 95% CI=1.062-3.933) were influencing factors of social isolation in maintenance hemodialysis patients (all P<0.05). Conclusions:The occurrence of social isolation in maintenance hemodialysis patients was closely associated with advanced age, high dialysis age, sedentary behavior, debilitation, and depressive status, suggesting that medical staff in hemodialysis centers can implement targeted interventions to prevent or improve the level of social isolation in patients based on relevant influencing factors.

Objective:To synthesize the findings of qualitative research on the treatment experience of cancer patients receiving immune checkpoint inhibitors therapy to provide a basis for developing relevant health education strategies and other supportive care interventions.Methods:Qualitative research on the treatment experience of cancer patients receiving immune checkpoint inhibitors therapy, published by May 2022, were searched in English and Chinese databases, including Cochrane Library, PubMed, Embase, PsycINFO, CINAHL, Web of Science, CNKI, Wanfang, VIP, and CBM. The quality of the included studies was evaluated by Joanna Briggs Institute Critical Appraisal Tool for qualitative studies. The research results were summarized and Meta-synthesis using the pooled integration method.Results:A total of 13 articles were included and 62 findings were grouped into 12 new categories according to their similarities. These 12 categories resulted in 4 synthesized findings: life was affected, facing multiple decision scenarios, presence of some unmet needs and gaining positive experiences and personal growth.Conclusions:Although patients experience some positive experiences, a large proportion of them experience significant health distress. Healthcare professionals should develop targeted health education with supportive care strategies on the basis of a comprehensive assessment.