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: Salt-processed Psoraleae Fructus (SPF) is widely used as a phytoestrogen-like agent in the treatment of osteoporosis. However, due to improper clinical use or misuse, resulting in liver damage. In this study, network pharmacology was employed to analyze the mechanism of cholestatic liver damage. An adeno-associated virus overexpressing SULT1E1 (rAAV8-SULT1E1) was constructed and the hepatotoxicity of SPF, psoralen, and isopsoralen was determined. METHODS: By utilizing three databases inclding TCMSP, TCMID, and BATMAN- TCM, the targets of the three databases were summarized, and a total of 45 psoralen compounds were included. Network pharmacology analysis was then performed. The adenoviral vectors were injected into the tail vein of C57BL6 mice to elucidate the role of SULT1E1 in SPF-induced cholestasis-mediated hepatotoxicity in vivo. SPF (10 g/kg), psoralen, and isopsoralen (50 mg/kg each) were intragastrically administered to mice for 30 d. B-ultrasound and samples were collected and examined for follow-up experiments. RESULTS: A total of 854 targets were predicted for 45 active components, with 151 cholestasis-mediated hepatotoxicity-related disease targets obtained for SPF. A total of 126 pathways were enriched based on KEGG pathway analysis, with the "estrogen signaling pathway" identified as one of the top 20 pathways. In terms of pathological hepatic changes, treated mice had visually swollen hepatocytes, dilated bile ducts, and elevated serum biochemical markers, which were more prominent in mice treated with isopsoralen than in those treated with other compounds. Notably, the overexpression of SULT1E1 could reverse liver damage in each treatment group. B-ultrasound was used to observe the size of the gallbladder in vivo. The size of the gallbladder was found to significantly increase on day 30 after treatment in the SPF-, psoralen-, and isopsoralen-treated groups, especially the SPF group. Compared with the expression levels in the negative control group (rAAV8-empty + con), the expression levels of FXR, Mrp2, Bsep, SULT1E1, SULT2A1, Ntcp, and Nrf2 decreased, whereas those of CYP7a1 and IL-6 increased in the SPF-, psoralen-, and isopsoralen-treated groups. CONCLUSION The overexpression of SULT1E1 could alleviate the decreased or increased expression of indicators, indicating that SULT1E1 is an important target gene for SPF-induced liver damage. The severity of liver damage was significantly lower in the rAAV8-SULT1E1 groups than in the rAAV8-empty groups.

Objective To observe the effects of a stepped early activity program combined with lower limb joint rehabilitation devices in mechanically ventilated patients in the intensive care unit(ICU).Methods Sixty mechanically ventilated patients admitted to the ICU of Tianjin First Central Hospital from October 2022 to June 2023 were selected as study subjects and randomly divided into an intervention group(n=30)and a control group(n=30)using a random number table.The control group received routine rehabilitation nursing combined with lower limb joint rehabilitation devices,while the intervention group was additionally treated with the stepped early activity program.The duration of mechanical ventilation,length of ICU stay,incidence of delirium,Medical Research Council(MRC)muscle strength scores,phase angle(PA),and skeletal muscle mass index(SMI)were compared between the two groups.Results The intervention group showed significantly shorter durations of mechanical ventilation and the length of ICU stay compared to the control group[mechanical ventilation time(days):9.20±4.51 vs.11.73±4.59,the length of ICU stay(days):10.73±5.37 vs.14.00±6.03,both P<0.05].Post-intervention MRC muscle strength scores,PA,and SMI significantly increased in both groups,with greater improvements observed in the intervention group[MRC muscle strength score:54.17±2.10 vs.50.17±3.51;PA(°):5.80±0.60 vs.5.49±0.54;SMI(kg/m2):6.87±0.46 vs.6.62±0.45,all P<0.05].No statistically significant difference was found in delirium incidence between the two groups[26.7%(8/30)vs.33.3%(10/30),P>0.05].Conclusion The combination of a stepped early activity program and lower limb joint rehabilitation devices effectively shortens mechanical ventilation time and the length of ICU stay,restores muscle strength,and promotes recovery in mechanically ventilated ICU patients,demonstrating significant clinical value.

Objective:To explore the configurational factors influencing the professional commitment of Master of Nursing Specialist (MNS) students and identify effective paths to enhance their professional commitment.Methods:A convenience sample of MNS students from six hospitals in Jiangsu Province, Shanghai City, and Anhui Province was surveyed between December 2023 and October 2024. Data were collected using a general information questionnaire, the Nurses' Professional Commitment Scale (NPCS), the Connor-Davidson Resilience Scale (CD-RISC-10), the Multidimentional Perceived Social Support (MSPSS), and the Vocational Outcome Expectation Scale (VOE-R). Fuzzy-set Qualitative Comparative Analysis (fsQCA) was used to explore the configurational influences on professional commitment.Results:A total of 332 questionnaires were distributed, and 302 valid responses were obtained (effective response rate: 90.1%). The mean NPCS score among respondents was (89.30±22.42), indicating a upper-middle level of professional commitment. The fsQCA results revealed that the frequency of night shift rotation was a necessary condition affecting professional commitment. A total of three distinct configurations (paths) were identified that can enhance the professional commitment of MNS students.Conclusions:The professional commitment of MNS students is influenced by multiple interacting factors. It is recommended that hospitals, universities, and nursing educators develop targeted interventions based on these identified configurations to improve professional commitment.

Objective To explore the definition and connotation of kinesiophobia in patients with heart failure,hence to provide a reference for clinical practice.Methods A systematic search was conducted on databases including CNKI,Wanfang Data,Web of Science,PubMed and Embase.Walker and Avant's concept analysis was applied to analyse the literature related to kinesiophobia in patients with heart failure.Results A total of 30 articles were included.The defining attributes of kinesiophobia in patients with heart failure were identified as emotional responses,cognitive biases,physical perceptions and avoidance behaviours.Antecedents included general demographic factors,disease-related factors,exercise self-efficacy,psychological factors and social support.Consequences included reduction in exercise adherence,decrease in physical function and increase in psychological burden.Conclusion The concept analysis of kinesiophobia in patients with heart failure can help healthcare providers with a better understanding and prevention of the kinesiophobia,and provides a reference for the researches in kinesiophobia in patients with heart failure.

Objective:To explore the configurational factors influencing the professional commitment of Master of Nursing Specialist (MNS) students and identify effective paths to enhance their professional commitment.Methods:A convenience sample of MNS students from six hospitals in Jiangsu Province, Shanghai City, and Anhui Province was surveyed between December 2023 and October 2024. Data were collected using a general information questionnaire, the Nurses' Professional Commitment Scale (NPCS), the Connor-Davidson Resilience Scale (CD-RISC-10), the Multidimentional Perceived Social Support (MSPSS), and the Vocational Outcome Expectation Scale (VOE-R). Fuzzy-set Qualitative Comparative Analysis (fsQCA) was used to explore the configurational influences on professional commitment.Results:A total of 332 questionnaires were distributed, and 302 valid responses were obtained (effective response rate: 90.1%). The mean NPCS score among respondents was (89.30±22.42), indicating a upper-middle level of professional commitment. The fsQCA results revealed that the frequency of night shift rotation was a necessary condition affecting professional commitment. A total of three distinct configurations (paths) were identified that can enhance the professional commitment of MNS students.Conclusions:The professional commitment of MNS students is influenced by multiple interacting factors. It is recommended that hospitals, universities, and nursing educators develop targeted interventions based on these identified configurations to improve professional commitment.

Objective To observe the effects of a stepped early activity program combined with lower limb joint rehabilitation devices in mechanically ventilated patients in the intensive care unit(ICU).Methods Sixty mechanically ventilated patients admitted to the ICU of Tianjin First Central Hospital from October 2022 to June 2023 were selected as study subjects and randomly divided into an intervention group(n=30)and a control group(n=30)using a random number table.The control group received routine rehabilitation nursing combined with lower limb joint rehabilitation devices,while the intervention group was additionally treated with the stepped early activity program.The duration of mechanical ventilation,length of ICU stay,incidence of delirium,Medical Research Council(MRC)muscle strength scores,phase angle(PA),and skeletal muscle mass index(SMI)were compared between the two groups.Results The intervention group showed significantly shorter durations of mechanical ventilation and the length of ICU stay compared to the control group[mechanical ventilation time(days):9.20±4.51 vs.11.73±4.59,the length of ICU stay(days):10.73±5.37 vs.14.00±6.03,both P<0.05].Post-intervention MRC muscle strength scores,PA,and SMI significantly increased in both groups,with greater improvements observed in the intervention group[MRC muscle strength score:54.17±2.10 vs.50.17±3.51;PA(°):5.80±0.60 vs.5.49±0.54;SMI(kg/m2):6.87±0.46 vs.6.62±0.45,all P<0.05].No statistically significant difference was found in delirium incidence between the two groups[26.7%(8/30)vs.33.3%(10/30),P>0.05].Conclusion The combination of a stepped early activity program and lower limb joint rehabilitation devices effectively shortens mechanical ventilation time and the length of ICU stay,restores muscle strength,and promotes recovery in mechanically ventilated ICU patients,demonstrating significant clinical value.

Objective To explore the definition and connotation of kinesiophobia in patients with heart failure,hence to provide a reference for clinical practice.Methods A systematic search was conducted on databases including CNKI,Wanfang Data,Web of Science,PubMed and Embase.Walker and Avant's concept analysis was applied to analyse the literature related to kinesiophobia in patients with heart failure.Results A total of 30 articles were included.The defining attributes of kinesiophobia in patients with heart failure were identified as emotional responses,cognitive biases,physical perceptions and avoidance behaviours.Antecedents included general demographic factors,disease-related factors,exercise self-efficacy,psychological factors and social support.Consequences included reduction in exercise adherence,decrease in physical function and increase in psychological burden.Conclusion The concept analysis of kinesiophobia in patients with heart failure can help healthcare providers with a better understanding and prevention of the kinesiophobia,and provides a reference for the researches in kinesiophobia in patients with heart failure.

Objective:To investigate the association and predictive value of serum biomarkers with carotid atherosclerosis(CAS)in the elderly population.Methods:The data used in this study were obtained from the China Hainan Centenarian Cohort Study(CHCCS), a prospective cohort that includes elderly individuals from community populations in Hainan Province.The baseline survey was conducted between 2014 and 2019.A total of 737 elderly individuals aged 80 to 100 were included in the analysis.The study examined various factors including questionnaires, physical examination data, liver and kidney function indicators(albumin, aspartate aminotransferase, alanine aminotransferase, total bilirubin, and glomerular filtration rate), blood cell counts(red blood cells, white blood cells, platelets, neutrophil count, lymphocyte count, and monocyte count), inflammatory markers(high-sensitivity C-reactive protein), and lipid metabolism markers(total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein AI, and apolipoprotein B).The objective was to explore the lipids of serum biomarkers and diagnostic performance of carotid atherosclerosis.Results:The prevalence of CAS in the elderly population was found to be 80.7%.Spearman's correlation analysis and a fully adjusted multivariate logistic regression model were used to examine the relationship between CAS and various factors in elderly patients.Result showed that systolic blood pressure, heart rate, and serum apolipoprotein B levels were significantly correlated with CAS[ OR(95% CI): 1.012(1.004-1.021), 0.998(1.011-1.024); 15.796(4.914-50.772), respectively; all P<0.001].Additionally, ROC curve analysis demonstrated that the combined application of serum apolipoprotein B, systolic blood pressure, and heart rate improved the predictive value of CAS in the elderly(Area under the curve: 0.820, 95% CI: 0.782-0.858; Sensitivity: 78.8%; Specificity: 86.8%; Positive likelihood ratio: 5.97; Negative likelihood ratio: 0.24). Conclusions:Our study discovered that serum apolipoprotein B is an autonomous risk factor for CAS among the elderly.The utilization of a specific set of biomarkers, in conjunction with other risk markers, holds potential as a promising strategy for evaluating CAS in the elderly population.

Objective To explore the changes in periretinal defocus and visual quality after femtosecond laser-assis-ted in situ keratomileusis(FS-LASIK).Methods Fifty-one myopic patients(102 eyes)who underwent FS-LASIK at the Ineye Hospital of Chengdu University of Traditional Chinese Medicine from March to May 2023 were selected for the study,including 27 females(54 eyes)and 24 males(48 eyes).The defocus around the retina was measured using a multispectral refraction topography,and the total refraction difference value(TRDV)was recorded.The refraction difference value(RDV)in four quadrants:superior RDV(RDV-S),inferior RDV(RDV-I),nasal RDV(RDV-N),and temporal RDV(RDV-T),as well as the RDV in the concentric ring areas corresponding to 10°,20°,30°,40°,and 53° from the fovea of the mac-ula(represented as RDV 0°-10°,RDV 10°-20°,RDV 20°-30°,RDV 30°-40°,and RDV 40°-53°,respectively)were also re-corded.The objective scattering index(OSI),Strehls ratio(SR),modulation transfer function(MTF)values(represen-ted as 10 c·d-1 MTF,20 c·d-1 MTF,and 30 c·d-1MTF,respectively)and cutoff frequencies(MTF cutoff)at the spa-tial frequencies of 10 c·d-1,20 c·d-1 and 30 c·d-1 were measured and recorded using a visual quality analysis system.The data of corneal vertical trefoil(Z3-3),vertical coma(Z3-1),horizontal coma(Z31),horizontal trefoil(Z33),vertical tetrafoil(Z4-4),vertical secondary astigmatism(Z4-2),spherical aberration(Z40),horizontal secondary astigmatism(Z42),horizontal tetrafoil(Z44),and total higher-order aberration(HOA)were measured and recorded using the iTrace aberration meter.The measurement data of patients before surgery,one month after surgery,and three months after sur-gery were compared,and their correlations were analyzed.Results TRDV,RDV-S,RDV-N,RDV 20°-30°,RDV 30°-40°,and RDV 40°-53° around the retina of patients decreased one month and three months after surgery compared with those be-fore surgery,and the differences were statistically significant(all P＜0.001).There were statistically significant differences in OSI,MTF cutoff,and 10 c·d-1 MTF among patients before surgery,one month after surgery,and three months after surgery(all P＜0.05).There were statistically significant differences in corneal Z3-3,Z3-1,Z31,Z33,Z4-4,Z4-2,Z40,Z42,Z44,and HOA among patients before surgery,one month after surgery,and three months after surgery(all P＜0.001).The Pearson correlation analysis results showed that,ΔRDV 0°-10° was positively correlated with ΔZ3-3,ΔZ31,ΔZ4-2,ΔZ40,and ΔZ42(all P＜0.05);ΔRDV 10°-20° was positively correlated with ΔZ4-4 and ΔZ4-2(both P＜0.05);ΔRDV 20°-30° was positively correlated with ΔZ4-4 and ΔZ44(both P＜0.05);ΔTRDV and ΔRDV 40°-53° were negatively correla-ted with ΔHOA(both P＜0.05).ΔRDV-S and ΔZ3-1 were negatively correlated with ΔHOA(both P＜0.05)and positively correlated with ΔZ44(P＜0.05);ΔRDV-N was positively correlated with ΔZ4-4(P＜0.05).Conclusion FS-LASIK can reduce periretinal hyperopic defocus in myopic patients,but it introduces corneal HOA,and there is a certain correlation between the two.