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 explore the mediation effect of emotional intelligence in social support and subjective happiness,and to provide practical guidance for scientific management of nursing talents in hemodialysis center.Methods Using a cross-sectional study,by a proportional stratified sampling method,from October 2022 to January 2023,800 hemodialysis nurses in Guangzhou area were selected as the respondents,using the general data adjustment table,general well-being schedule(GWB),social support rating scale(SSRS),and wong law emotional intelligence scale(WLEIS-C).The pearson correlation was used to analyze the correlation between emotional intelligence,social support and subjective happiness of hemodialysis nurses in Guangzhou;the process macro program was used to explore the mediation effect of emotional intelligence in social support and subjective happiness in Guangzhou.Results 707 valid questionnaires were collected,and the effective recovery rate was 88.38%.The total score of subjective well-being of hemodialysis nurses in Guangzhou was(75.67±8.17),the total score of emotional intelligence(82.29±16.20),and the total score of social support(38.76±8.40).The total score of social support was positively associated with the total score of subjective well-being(r=0.517,P<0.01)and the total score of emotional intelligence(r=0.633,P<0.01),the total score of emotional intelligence was positively related to the total score of subjective well-being(r=0.634,P<0.01).Social support had a direct effect on subjective well-being(β=0.165,95%CI:0.103-0.261),and indirectly affected it through the partial mediation effect of emotional intelligence(β=0.095,95%CI:0.069-0.142),and the indirect mediation effect accounted for 36.54%of the total effect.Conclusion Guangzhou area hemodialysis nurses subjective well-being is in upper level,and emotional intelligence in hemodialysis nurses social support and subjective happiness plays intermediary effect,managers should focus on hemodialysis nurses emotional intelligence,take various measures to improve their emotional intelligence level,enhance social support,so as to improve hemodialysis nurses subjective well-being.

Objective:To investigate the current nutrition support status of hospitalized small for gestational age infants born late preterm in hospitals of Beijing, and analyze the influencing factors.Methods:Clinical data of late preterm infants from 25 medical units in Beijing between October 2015 and October 2017 was collected and analyzed. Infants were assigned into two groups according to the relationship between their gestational age and birth body weight as small for gestational age(SGA) group and not small for gestational age(non-SGA) group, to compare their nutritional status and explore the related influential factors.Results:Totally, 1 347 late preterm infants were enrolled, including 730 males and 617 females, 151 in SGA group and 1 196 in non-SGA group. The data showed that the rate of exclusive breast-feeding was higher (5.3% vs 4.5%, P<0.01), and the increasing of milk volume was slower [11.0 vs 12.1 ml/(kg·d), P=0.003] in SGA group. More parenteral nutrition was used (77.5% vs 53.1%, P<0.01), and the duration of parenteral nutrition was longer (5.0 vs 2.0 days, P<0.01) in SGA group. The birth weight(1 940 vs 2 490 g, P<0.01), the lowest body weight(1 890 vs 2 400 g, P<0.01) and the discharged body weight(2 135 vs 2 530 g, P<0.01)were lower in SGA group. The SGA group showed lower body weight loss(3.1% vs 8.0%, P=0.015), slower weight growth(13.3 vs 33.0 g/d, P<0.01), and longer length of hospital stay (11.0 vs 8.0 days, P<0.01). In SGA group, the milk volume at discharge [145.6 vs 122.2 ml/(kg·d), P<0.01] and the caloric of enteral feeding at discharge [443.9 vs 384.1 kJ/(kg·d), P<0.01] were higher, the rate of infants who regained their birth weight during hospitalization(78.8% vs 57.9%, P<0.01) was higher, and the rate of ones who achieve full enteral feeding (31.8% vs 16.6%, P<0.01) was higher. A Cox regression analysis in which we set infants can achieve full enteral feeding as goal showed that independent factors associated with full enteral feeding at discharge in SGA group included the increasing of enteral feeding, the duration of parenteral nutrition, whether the length of hospital stay longer than 7 days or not whether exclusive breastfeeding and whether the mothers of enrolled infants were diagnosed gestational diabetes mellitus or placental abruption during pregnancy ( P<0.05). Conclusions:Infants in SGA group show slower increasing of milk volume and lower caloric amount of enteral feeding. More parenteral nutrition is used, and the duration of parenteral nutrition is longer in SGA group. Due to the longer length of hospital stay in SGA group, the milk volume and the caloric of enteral feeding at discharge are higher, more infants regain their birth weight during hospitalization, and more infants achieve full enteral feeding at discharge. Despite of higher portion of parenteral nutrition, infants in SGA group show slower weight growth and lower body weight at discharge.

Objective:To investigate the status and influencing factors of enteral nutrition support in late preterm infants (34-36 +6 gestational weeks) treated in different grades of hospitals in Beijing. Methods:This was a prospective study involving late preterm infants treated in 25 hospitals in Beijing from October 2015 to October 2017. Data about nutritional management and nutrition-related complications were recorded. Exclusive breastfeeding status of the infants by gestational age(GA) and hospital levels was analyzed. The achievement of full enteral feeding and the potential influencing factors were also analyzed. t-test, Mann-Whitney U test, analysis of variance (ANOVA), Kruskal-Wallis test and Chi-square test were used for statistical analysis. Logistic regression and Cox regression analysis were used in multivariate analysis. Results:(1) A total of 1 463 late preterm infants with GA of 35.6±0.8 (ranging from 34.9 to 36.1) weeks was enrolled in this study. Compared with the infants with GA of 35-35 +6 and 36-36 +6 weeks, those born at 34-34 +6 gestational weeks had longer hospital stay [10 (8-13) vs 8 (7-10) and 7 (6-9) d, both P<0.05], greater loss of minimum weight [4.3% (2.6%-6.3%) vs 3.8% (2.0%-5.6%) and 3.3% (1.9%-5.5%), both P<0.05], higher incidence of apnea [5.3% (20/369) vs 2.1% (12/566) and 1.3% (7/528), both P<0.05] and respiratory distress syndrome (RDS) [7.1% (28/369) vs 3.0% (17/566) and 3.2% (17/528), both P<0.05], and lower percentage of failure to regain birth weight at discharge [32.5% (120/369) vs 38.7% (219/566) and 47.9% (253/528), both P<0.05]. Only the incidence of premature rupture of membranes among all maternal complications during pregnancy had statistical difference between 34-34 +6, 35-35 +6 and 36-36 +6 GA groups [6.2% (23/369) vs 12.7% (72/566) and 11.9% (63/528), χ2=10.244, P=0.007]. (2) The rate of enteral feeding increment in hospital was 13.7 (10.5-17.3) ml/(kg·d) and 46.0% (673/1 463) of the infants were fed formula. The exclusive breastfeeding rate increased from 4.5% (66/1 463) during hospitalization to 14.4% (211/1 463) at discharge. The breastfeeding rate at discharge varied widely among the 25 hospitals ( χ2=327.893, P<0.001) ranging from 32% to 0. (3) Logistic regression analysis demonstrated that gestational diabetes mellitus ( OR=2.426, 95% CI: 1.075-5.437, P=0.033) and premature rupture of membranes ( OR=8.726, 95% CI: 1.193-63.802, P=0.033) were the prenatal risk factors influencing the exclusive breastfeeding in late preterm infants. Enteral nutrition achieving 150 ml/(kg·d) and 120 kcal/(kg·d) (1 kcal=4.184 kJ) were noted for 28.4% (416/1 463) and 19.2% (281/1 463) of the late preterm infants at discharge, respectively. Cox regression analysis showed that hospital grades ( HR=1.470, 95% CI: 1.030-2.098, P=0.034), the length of hospital stay ( HR=1.162, 95% CI: 1.097-1.231, P<0.001), birth weight ( HR=0.946, 95% CI: 0.898-0.995, P=0.003), exclusive breastfeeding ( HR=2.354, 95% CI:1.031-5.374, P=0.042), feeding intolerance ( HR=3.677, 95% CI: 1.201-11.253, P=0.023), parenteral nutrition ( HR=1.900, 95% CI: 1.379-2.616, P<0.001), and the rate of enteral feeding advancement ( HR=1.426, 95% CI: 1.369-1.484, P<0.001) were independent factors associated with full enteral feeding at discharge. Conclusions:Exclusive breastfeeding rate in late preterm infants is low and enteral nutrition support varies greatly in different hospitals. The rate of enteral feeding increment is slow for hospitalized late preterm infants and most fail to achieve full enteral feeding at discharge. Gestational diabetes mellitus and premature rupture of membranes are prenatal risk factors affecting breastfeeding of late preterm infants. Those with low birth weight, exclusive breastfeeding in hospital, feeding intolerance, parenteral nutrition support, longer hospital stay or rapid enteral feeding advancement are more likely to achieve full enteral feeding at discharge.

OBJECTIVE: To observe the effects of nilotinib on silicon dioxide(SiO_2)-induced cell proliferation and collagen synthesis in human fetal lung fibroblast-1(HFL-1) cells and to explore the related mechanism. METHODS: ⅰ) HFL-1 cells were induced with different doses of SiO_2 suspension(0, 5,10, 25, 50 and 100 mg/L) for 24.0 hours. The expression of transforming growth factor-β1(TGF-β1), C-Abl, and platelet-derived growth factor receptor(PDGFR) was detected by Western blot, and the dose of SiO_2 in subsequent experiments was screened. ⅱ) HFL-1 cells were randomly divided into 6 groups: 1) the control group: no treatment; 2) the solvent control group: cells were treated with 0.10% dimethyl sulfoxide; 3) the SiO_2 stimulation group: cells were induced with SiO_2 suspension at a dose of 50 mg/L for 24.0 hours; 4)-6) the nilotinib groups: cells were induced with SiO_2 suspension at a dose of 50 mg/L for 24.0 hours and treated with nilotinib at the concentration of 5, 10, or 15 mmol/L for 24.0 hours. Cell proliferation was detected by MTS assay. The TGF-β1 protein secreted by cells was measured using enzyme linked immunosorbent assay. The expression of TGF-β1, C-Abl, platelet derived growth factor(PDGF), PDGFR and collagen typeⅠproteins was measured by Western blot. RESULTS: ⅰ) The dose of the SiO_2 in the experiments was set to 50 mg/L. ⅱ) The cell proliferation rate of HFL-1 cells in the SiO_2 stimulation group and the 3 nilotinib groups was higher than that in control group and solvent control group(P<0.05). The proliferation rates of HFL-1 cells in 10 and 15 mmol/L nilotinib groups were lower than that in SiO_2 stimulation group(P<0.05). The level of TGF-β1 and the protein relative expression levels of TGF-β1, collagen typeⅠ, C-Abl, PDGFR and PDGF in HFL-1 cells of SiO_2 stimulation group were higher than those in control group and solvent control group(P<0.05). The above indexes of HFL-1 cells in 15 mmol/L nilotinib group were lower than that in SiO_2 stimulation group(P<0.05); the above indexes of HFL-1 cells in 5 mmol/L nilotinib group were not significantly different from those in SiO_2 stimulation group(P>0.05). The level of TGF-β1 and the relative expression level of C-Abl protein in HFL-1 cells of 10 mmol/L nilotinib group were lower than those in SiO_2 stimulation group(P<0.05). CONCLUSION: Nilotinib can inhibit the proliferation of HFL-1 cells and reduce the expression of collagen typeⅠprotein induced by SiO_2. This process may be achieved by inhibiting tyrosine kinase-mediated signaling pathway.

Objective Pulmonary fibrosis is a progressive chronic lung disease with a high incidence.Although the path of the disease has not been fully elucidated,the pathogenesis of the disease is roughly similar.Tyrosine kinases are involved in a series of signaling pathways that are critical for cell homeostasis.Substantial evidence from in vitro studies and experimental animal models suggests that tyrosine kinases play a role in promoting the development and progression of pulmonary fibrosis,and tyrosine kinase inhibitors have shown good anti-fibrosis and anti-inflammatory effect in animal models of pulmonary fibrosis.

Objective To investigate the correlation of spinal mechanical imbalance and thoraco-dorsal pain of ankylosing spondylitis (AS). Methods The clinical data of 90 patients with AS were collected. Patients were divided into two groups according to the presence of thoracodorsal pain: the AS with thoraco-dorsal pain group (30 cases) and the AS without thoraco-dorsal pain group (60 cases). Clinical symptoms, Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis function index (BASFI), Bath ankylosing spondylitis measurement index (BASMI), ankylosing spondylitis disease activity (ASDAS), and spinal mechanical function and nuclear myocardial force test were compared using t-test, one-way analysis of variance (ANOVA) analysis and Spearman correlation analysis. Results ① There were differences between thoraco-dorsal pain group and patients without thoracodorsal pain group at the time of back muscle strength [(0.82±0.41) min vs (1.33±0.74) min, F=12.372, P=0.001]; ②Thoraco-dorsal pain in the AS group was mainly the middle and lower thoracic vertebrae, such as the inflammation of rib head and rib transverse process, facial arthritis, and spinous ligaments, etc. And the missed diagnosis rate of magnetic resonance imagin (MRI) was high. ③ In healthy control group, the anterior flexion strength of thoracodorsal pain group was signific-antly different from that of patients without thoracodorsal pain [(92.1 ±46.3) Nm vs (126.6±35.7) Nm, F=6.440, P=0.002]. ④ There was significant difference in spinal strength as well as left and right rotation strength between the thoracodorsal pain group and patients without thoracodorsal pain [(1.18 ±0.22) vs (1.05 ±0.17), F=10.044, P<0.01];⑤In the thoraco-dorsal pain group, the right/left index was related to BASDAI (r=-0.522, P=0.004). For spinal mobility, the right/left index was related to cross cutting faces to right ( r=0.435, P=0.021), cross cutting faces to left (r=0.528, P=0.004). In spinal strength, the right/left index was related to left turn (r=0.57, P=0.001); right lateral flexion (r=0.368, P=0.049) and left lateral flexion (r=0.369, P=0.049). Conclusion The thoracodorsal pain of AS is dominated by the middle and lower thoracic vertebrae, and the missed diagnosis rate of MRI is high. The imbalance of the left and right side of the spine is one of the factors of the thoracic back pain in AS.

Objective To investigate the effect of aerobic exercise combined with routine rehabilitation therapy on cardiorespiratory exercise function and rehabilitation efficacy in stroke patients with hemiplegia.Methods Thirty consecutive stroke patients with the first-ever hemiplegia were enrolled prospectively.They were randomly assigned to an experimental group (n=13) or a control group (n=13) according to the random number table (n=15 in each group).Four patients withdrew,and finally 26 patients completed the study (n=13 in each group).The two groups of patients were given routine rehabilitation therapy.On the basis of routine rehabilitation therapy,the experimental group was also treated with aerobic exercise training,once a day,30 min each time for 4 weeks.The evaluations of cardiopulmonary exercise tests were performed on both groups before treatment and after 4 weeks of treatment (peak oxygen uptake [VO2peak]),anaerobic threshold [AT],peak minute ventilation [VEpeak]),and motor function (Fugl-Meyer assessment scale [FMA],activities of daily living (Barthel index [BI]) were performed.The differences between the two groups before and after treatment were compared.Results (1)Cardiopulmonary exercise test results:Compared with before treatment,VO2peak,AT,and VEpeak were increased significantly (16±4 ml/[kg·min] vs.13±3 ml/[kg·min],12.9±2.5 kg·min vs.10.0±2.7 ml/[kg·min],41±12 L/min vs.34±9 L/min,t=9.668,4.328,and 3.662,respectively,all P<0.01).There were no significant differences in VO2peak,AT,and VEpeak (14±4 ml/[kg·min] vs.14±4 ml/[kg·min],11.8±2.6 ml/[kg·min] vs.11.5±2.9 ml/[kg·min],29±8 L/min vs.28±6 L/min) in patients of the control group between before treatment and after treatment.There were no significant differences (t=0.863,0.583,and 0.314,respectively,all P>0.05).The differences in VO2peak,AT,and VEpeak in the patients of the control group before and after treatment were 0.4 (0.2,0.6),0.1 (-0.5,0.7 ml/kg·min) and 0 (-2.5,5.0 L/min),respectively.The differences of VO2peak,AT,and VEpeak in patients of the experimental group before and after treatment were 3.0 (2.2,3.9 ml/[kg·min],2.7 (1.8,5.3 ml/[kg·min],and 7.0 (1.0,13.0 L/min),respectively.There were significant differences in VO2peak,AT,and VEpeak before and after treatment between the two groups (Z=4.287,3.721,and 2.236,respectively,P<0.05).(2) FMA score and BI evaluation results:Compared with before treatment,the FMA score and Barthel index after treatment in patients of the experiment group were 70±24 vs.52±28 and 78±20 vs.60±28 respectively,t=4.076 and 4.239 respectively,P<0.01).Compared with before treatment,the FMA score and BI in the control group after treatment were improved significantly (68±25 vs.60±27 and 69±22 vs.59±26 respectively,t=3.168 and 5.436 respectively,all P<0.05).The FMA score and the difference of BI in the control group before and after treatment were 5.0 (2.0,12.0) and 10.0 (5.0,15.0) respectively,and those of the experimental group before and after treatment were 10.0 (4.5,32.0) and 11.0 (10.0,27.5) respectively,and there were no significant differences between the two groups (Z=1.393,1.352,all P>0.05).Conclusion On the basis of routine rehabilitation therapy,stroke patients with hemiplegia increasing aerobic exercise training may improve their cardiopulmonary exercise function.

Objective To quantitatively assess the cardiopulmonary exercise function of spinal cord injury (SCI) patients and observe the effect of aerobic exercise on cardiopulmonary function, motor function and activities of daily living. Methods From December, 2014 to June, 2016, 34 incomplete SCI patients (ASIA C and D) and 23 healthy controls received cardiopulmonary exercise test (CPET). SCI pa-tients were randomly divided into conventional rehabilitation group (n=17) and aerobic exercise group (n=17). The aerobic exercise group received aerobic exercise for four weeks. They were assessed with CPET, motor and sensory function, walking index for spinal cord injury II (WISCI II) and spinal cord independence measure (SCIM) before and four weeks after training. Results Oxygen uptake (VO2)peak, anaerobic threshold (AT), metabolic equivalent of energy (METpeak), VO2/heart rate (HR)peak, respiratory exchange rate (RER)peak, minute ventilation (VE)peak, work rate (WR)peak and systolic blood pressure (SBP)peak were lower in the patients than in the controls (t>2.714, P<0.05). VO2peak、AT、METpeak、VO2/HRpeak、WRpeak increased in the aerobic exercise group after training (t>2.431, P<0.05). METpeak and WRpeak improved in the conventional rehabilitation group after training (t>3.282, P<0.01). The scores of motor in ASIA and SCIM improved in both groups after training (t>2.985, P<0.05). Conclusion The cardiopulmonary function decreased in incomplete SCI patients, which could be improved by moderate intensity aerobic exercise.

Objective To investigate the clinical significance of soluble CD40 ligand (sCD40L ) and lipoprotein associated phospholipase A2 (Lp-PLA2 ) in the assessment of coronary artery severity and risk classification in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS).Methods Of the 9 6 patients with coronary heart disease diagnosed by coronary angiography,2 8 patients had stable angina pectoris (SAP),38 patients unstable angina pectoris (UAP)and 30 patients acute non-ST-segment elevation myocardial infarction (NSTEMI).Another 30 patients with non-coronary heart disease (NC)served as controls.The sCD40L and Lp-PLA2 levels were determined by enzyme-linked immune sorbent assay (ELISA)method.The Gensini score was used to assess the severity of coronary artery and analyze the correlation with sCD40L and Lp-PLA2.The correlation of sCD40L and Lp-PLA2 with GRACE risk score was analyzed too.Results ① sCD40L was significantly higher in NSTEMI and UAP groups than in SAP and NC groups (P<0 .0 5 ),but there was no significant difference between NSTEMI and UAP groups (P>0 .0 5 )or SAP and NC groups (P>0 .0 5 ).Lp-PLA2 was significantly higher in NSTEMI group than in UAP,SAP and NC groups (P<0.05).Lp-PLA2 was significantly higher in UAP group than in SAP and NC groups (P<0.05).② We found that sCD40L had obvious correlation with Lp-PLA2 (r=0.284, P<0.01),Gensini score (r=0.213,P<0.05),and GRACE (r=0.224,P<0.05).Lp-PLA2 was significantly correlated with Gensini score (r=0.270,P<0.05),and GRACE (r=0.323,P<0.01).③ Multivariate logistic regression analysis showed that Lp-PLA2 was independently associated with NSTE-ACS (P<0.05).Conclusion The sCD40L and Lp-PLA2 which were significantly elevated in NSTE-ACS are correlated with the severity of coronary artery disease.The two indexes indicate the instability of atherosclerotic plaque;thus they can be used as predictors of risk assessment in coronary heart disease.