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.

OBJECTIVES: To construct vocal recognition classification models using 6 machine learning algorithms and vocal emotional characteristics of individuals with subthreshold depression to facilitate early identification of subthreshold depression. METHODS: We collected voice data from both normal individuals and participants with subthreshold depression by asking them to read specifically chosen words and texts. From each voice sample, 384-dimensional vocal emotional feature variables were extracted, including energy feature, Meir frequency cepstrum coefficient, zero cross rate feature, sound probability feature, fundamental frequency feature, difference feature. The Recursive Feature Elimination (RFE) method was employed to select voice feature variables. Classification models were then built using the machine learning algorithms Adaptive Boosting (AdaBoost), Random Forest (RF), Linear Discriminant Analysis (LDA), Logistic Regression (LR), Lasso Regression (LRLasso), and Support Vector Machine (SVM), and the performance of these models was evaluated. To assess generalization capability of the models, we used real-world speech data to evaluate the best speech recognition classification model. RESULTS: The AdaBoost, RF, and LDA models achieved high prediction accuracies of 100%, 100%, and 93.3% on word-reading speech test set, respectively. In the text-reading speech test set, the accuracies of the AdaBoost, RF, and LDA models were 90%, 80%, and 90%, respectively, while the accuracies of the other 3 models were all below 80%. On real-world word-reading and text-reading speech data, the classification models using AdaBoost and Random Forest still achieved high predictive accuracies (91.7% and 80.6% for AdaBoost and 86.1% and 77.8% for Random, respectively). CONCLUSIONS Analyzing vocal emotional characteristics allows effective identification of individuals with subthreshold depression. The AdaBoost and RF models show excellent performance for classifying subthreshold depression individuals, and may thus potentially offer valuable assistance in the clinical and research settings.
Humans ; Machine Learning ; Emotions ; Depression/diagnosis* ; Algorithms ; Voice ; Support Vector Machine ; Male ; Female

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.

This paper reports a case of a patient with sleep-related painful erections treated by acupuncture combined with abdominal vibration therapy. The main symptom was repeated painful penile erections during nighttime sleep. The syndrome was differentiated as "water failing to nourish wood" and "liver qi stagnation". Acupuncture was applied at Baihui (GV20), Sishencong (EX-HN1), Guanyuan (CV4), and bilateral Neiguan (PC6), Hegu (LI4), Taichong (LR3), Taixi (KI3), Guilai (ST29), Yongquan (KI1), Yanglingquan (GB34), and Sanyinjiao (SP6). The treatment was combined with abdominal vibration therapy. Treatment was given once daily, five times per week. After the first treatment, the severity and duration of nocturnal erection pain were reduced, and sleep quality was improved. After two weeks of treatment, nocturnal erection pain persisted but became tolerable, with significantly shortened duration.
Humans ; Male ; Acupuncture Points ; Acupuncture Therapy ; Erectile Dysfunction/physiopathology* ; Penile Erection ; Sleep

Objective To discuss the correlation between free prostate specific antigen(fPSA),serum ferritin(SF),blood uric acid(SUA)levels and Gleason grading in patients with prostate cancer(PCa).Methods The clinical data of 61 patients with prostate biopsy treated in 411 Hospital of Shanghai University from January to December of 2023 were retrospectively analyzed.According to the results of puncture,the patients were divided into benign prostatic hyperpla-sia(BPH)group(31 cases)and PCa group(30 cases).The levels of fPSA,SF and SUA in patients and Gleason grade in biopsy cases were analyzed.The correlation between fPSA,SF and SUA levels and Gleason grade was analyzed by the method of Spearman.And the diagnostic efficacy of fPSA,SF and SUA levels on PCa was analyzed by receiver operating characteristic curve(ROC).Results The levels of fPSA,SF and SUA in PCa group were significantly higher than those in BPH group(P＜0.05).There were statistically significant differences in levels of fPSA SF and SUA in PCA patients with different Gleason grades(P＜0.05).With the specificity reaching 96.08％and sensitivity reaching 94.35％,the ar-ea under the curve(AUC)of the combined fPSA,SF and SUA levels in the diagnosis of PCa was 0.982,which was higher than that of the single fPSA,SF and SUA levels(P＜0.05).SF and SUA levels in PCa patients were positively correlated with Gleason grade(P＜0.05),while fPSA levels were not correlated with Gleason grade(P＞0.05).Conclusion The levels of SF and SUA in PCa patients are positively correlated with Gleason grade,which can be used as an important index to predict Gleason grade in PCa patients.

Objective To investigate the expression characteristics and clinical significance of endothelial cell-derived extracellular vesicles(EC-EVs)in the peripheral blood of patients with sep-sis-induced cardiomyopathy(SIC).Methods A total of 143 sepsis patients were enrolled and divid-ed into cardiomyopathy group(n=72)and non-cardiomyopathy group(n=71)based on occurrence of SIC.Peripheral blood samples were collected from patients in both groups upon admission for isola-tion and identification of EC-EVs.The number of EC-EVs,apoptosis,and the activity and expression levels of caspase-1 in EC-EVs were compared between the two groups.Spearman correlation analysis was used to assess the correlations of the number of EC-EVs,caspase-1 activity,and N-terminal pro-brain natriuretic peptide(NT-proBNP)with cardiac troponin Ⅰ(cTnⅠ).Multivariable Logistic regres-sion analysis was conducted to explore the factors influencing the occurrence of SIC in sepsis patients.Receiver operating characteristic(ROC)curves were plotted to analyze the predictive value of the number of EC-EVs and caspase-1 activity for SIC.Results EC-EVs with a diameter of approximately 100 nm,intact membrane structure,and expression of extracellular vesicles(EVs)marker molecules(CD9,CD63,CD81)were successfully isolated from samples in both groups.The cardiomyopathy group had significantly higher numbers of EC-EVs in peripheral blood,EC-EV apoptosis levels,caspase-1 activity,and protein expression levels compared to the non-cardiomyopathy group(P＜0.05).Spearman correlation analysis revealed positive correlations between the number of EC-EVs and NT-proBNP(r=0.603,0.685,P＜0.001),and between caspase-1 activity and cTnⅠ(r=0.474,0.711,P＜0.001).Multivariable Logistic regression analysis showed that the number of EC-EVs,caspase-1 activity,NT-proBNP levels,and cTnⅠ levels were all independent influencing factors for the occurrence of SIC in sepsis patients(P＜0.05).The ROC curves indicated that the areas under the curve for predicting SIC based on the number of EC-EVs and caspase-1 activity in peripheral blood were 0.721 and 0.858,respectively.Conclusion The number of EC-EVs and caspase-1 activity in EC-EVs in the peripheral blood of SIC patients are significantly increased,and are closely related to cardiac function and myocardial injury in sepsis patients.Thus,they have the potential to become biomarkers for predicting SIC.

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 explore the effects of mechanical ventilation（MV）at birth transition on lung pathophysiology and pathobiology in a very preterm animal model.Methods:Based on the model of respiratory distress syndrome（RDS）in very preterm rabbits at gestational age 26（term 31）days well established by the research group using perinatal medication and lung-protective ventilation strategies（very low tidal volume 1-3 mL/kg），we conducted a secondary data analysis. The studied rabbits were re-grouped according to the MV length（≤3 h，3-6 h，6-9 h，9-12 h，and >12 h）. The changes in lung mechanics，histopathology，phospholipid biochemistry，and mRNA relative expression of inflammatory/growth factor in lung tissue were evaluated over the time course of MV. The trend of each variable was tested by ANOVA trend test（ F trend）and Jonckheere-Terpstra trend test（ J-T value）with corresponding P value. Results:With the prolonged MV length，there was improved mean dynamic compliance of respiratory system（ F trend=16.722， P trend<0.001），along with decreased mean peak inspiratory pressure（ F trend =42.226， P trend<0.001）. The content of total phospholipids，disaturated phosphatidylcholine（ J-T=1 222，1 197， P trend=0.018，0.034，respectively）and total protein（ J-T=1 247 ，P trend= 0.009）in bronchoalveolar lavage fluid gradually increased. The wet lung weight in the ≤3 h group was significantly higher than in the other groups（ F=6.819， P<0.001）. The lung injury score（total，or hemorrhage，or inflammation）had progressive exacerbation in the ≤3 h，3-6 h and 6-9 h groups. The lung tissue mRNA expression of major proinflammatory cytokines increased modestly over the time groups in contrast to decreased expression of growth factors，of which the change of keratinocyte growth factor reached statistical significance（ J-T=531， P trend =0.034）. Conclusion:In the 26-day very preterm rabbits，with prolonged MV time，the content of surfactant phospholipid in the alveolar increased gradually，the lung compliance and lung fluid clearance gradually improved. Nevertheless，ventilator-induced lung injury remained evolving. The study warrants further study on the pathogenesis and protective strategies of early postnatal acute lung injury and chronic lung disease.

Objective To discuss the correlation between free prostate specific antigen(fPSA),serum ferritin(SF),blood uric acid(SUA)levels and Gleason grading in patients with prostate cancer(PCa).Methods The clinical data of 61 patients with prostate biopsy treated in 411 Hospital of Shanghai University from January to December of 2023 were retrospectively analyzed.According to the results of puncture,the patients were divided into benign prostatic hyperpla-sia(BPH)group(31 cases)and PCa group(30 cases).The levels of fPSA,SF and SUA in patients and Gleason grade in biopsy cases were analyzed.The correlation between fPSA,SF and SUA levels and Gleason grade was analyzed by the method of Spearman.And the diagnostic efficacy of fPSA,SF and SUA levels on PCa was analyzed by receiver operating characteristic curve(ROC).Results The levels of fPSA,SF and SUA in PCa group were significantly higher than those in BPH group(P＜0.05).There were statistically significant differences in levels of fPSA SF and SUA in PCA patients with different Gleason grades(P＜0.05).With the specificity reaching 96.08％and sensitivity reaching 94.35％,the ar-ea under the curve(AUC)of the combined fPSA,SF and SUA levels in the diagnosis of PCa was 0.982,which was higher than that of the single fPSA,SF and SUA levels(P＜0.05).SF and SUA levels in PCa patients were positively correlated with Gleason grade(P＜0.05),while fPSA levels were not correlated with Gleason grade(P＞0.05).Conclusion The levels of SF and SUA in PCa patients are positively correlated with Gleason grade,which can be used as an important index to predict Gleason grade in PCa patients.