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.

Acute ischemic stroke(AIS)is associated with high mortality and disability rates,presenting a substantial challenge to global public health challenge.Intravenous thrombolysis(IVT)is recognized as a cornerstone of early AIS treatment and is recommended as the standard therapeutic approach by both national and international guidelines.However,the clinical efficacy of IVT remains suboptimal due to several limitations,including a narrow therapeutic time window and the inevitable activation of the coagulation system and platelet aggregagation during thrombolysis.These factors may contribute to adverse outcomes such as early neurological deterioration(END)and vascular re-occlusion.Antiplatelet therapy(APT),which inhibits platelet aggregations,reduces microthrombus formation,and stabilizes the vascular endothelium with multifaceted mechanisms,has emerged as a promising adjunctive strategy to IVT,offering potential synergistic effects.This review summarized the latest evidence from both domestic and international studies,focusing on the mechanisms of APT,recent clinical advancements in IVT combined with APT,and the safety and efficacy of APT administration at different time windows relative to IVT.Emphasis is placed on the influence of various antiplatelet agents,dosing regimens,and initiation timing on therapeutic outcomes,alongside a comprehensive evaluation in the context of current guideline recommendations and clinical practice.Current guidelines recommend initiating APT 24 h after IVT,following imaging confirmation to exclude the risk of intracranial hemorrhage.However,the efficacy and safety of earlier APT initiation remain inconclusive.Individualized treatment strategies,such as early administration of low-dose,short-acting APT or combination therapy in specific patient subgroups,may effectively balance therapeutic benefits and risks.The adjunctive use of APT in IVT holds promise for enhancing efficacy and improving clinical outcomes,but precise stratification of safety and efficacy is essential.Future research should focus on optimizing combination IVT and APT strategies through individualized patient profiling,appropriate drug selection,and dynamic imaging monitoring to achieve precision management in AIS treatment.

To analyze the clinical data of patients with recurrent Clostridioides difficile infection(rCDI)in the southwestern region,and help clinicians identify high-risk populations early and adopt appropriate treatment strate-gies.Methods Clinical data of rCDI cases from a tertiary first-class hospital in southwest China from July 2019 to June 2024 were collected,and their host-related risk factors,exogenous risk factors,treatment schemes,and end-point outcomes were analyzed.Results In the past five years,a total of 26 cases of rCDI were detected from a ter-tiary first-class hospital in southwest China,accounting for 4.04％of the total positive cases(n=643)detected during the same period.19.23％of the recurrent patients experienced a second recurrence.The median age of rCDI patients was 66.5 years old,with males accounting for 73.08％.The major comorbidity included diabetes mellitus(34.62％),malignant tumors(30.77％),and chronic renal diseases(23.08％).In the 8 weeks before the first on-set of rCDI in patients,the top three drugs used were β-lactam and enzyme inhibitor compound(69.23％),proton pump inhibitors(65.38％),and carbapenems(46.15％).In the initial treatment of recurrent patients,3.85％(1/26)of the cases were treated with metronidazole,19.23％(5/26)of the cases received non-standard vancomy-cin/norvancomycin treatment in usage or dosage,46.15％(12/26)of the cases received treatment with course less than 10 days.In the treatment of the first recurrence,34.78％(8/26)of the cases received treatment with course less than 10 days.Conclusion For elderly patients and patients with diabetes mellitus,malignant tumors,and chronic renal diseases,who have used β-lactam and enzyme inhibitor compound,proton pump inhibitors,carbapene-ms within 8 weeks before disease onset,standard dose and treatment course of vancomycin or norvancomycin are recommended under permitted conditions,so as to reduce the risk of recurrence.

Objectives To identify key clinical factors influencing recurrence in osteosarcoma patients,to construct and validate a Nomogram-based recurrence risk prediction model,thereby providing a quantitative tool for clinical decision-making and recurrence prevention/control.Methods Clinical data of 469 osteosarcoma patients admitted to Yunnan Cancer Hospital between 2013～2022 were retrospectively collected.Statistical analysis was performed using R software(version 4.3.2).Potential influencing factors were initially screened via univariate analysis and LASSO regression analysis.Independent predictors of osteosarcoma recurrence were then identified using multivariate logistic regression analysis.Based on the identified independent factors,a Nomogram prediction model for recurrence risk was constructed.The area under the receiver operating characteristic curve(AUC)was used to evaluate the model's discriminative ability.Results Among the entire cohort,68 patients experienced recurrence,yielding a recurrence rate of 14.50%.Multivariate analysis identified the following as independent predictors of recurrence:Primary Tumor Location:Tibial lesions(P=0.009)were associated with a significantly lower recurrence risk compared to femoral lesions(OR=0.297),while lesions in"Other Bones"(P=0.008)carried a significantly higher risk(OR=3.294).Biopsy Method:Needle biopsy(P=0.033)was associated with a significantly lower recurrence risk compared to open biopsy(OR=0.461).Lung Metastasis Status:Patients with lung metastasis(P<0.001)had a significantly higher recurrence risk than those without(OR=11.873).Lymphocyte Count:A higher lymphocyte count(P=0.001)was a protective factor,associated with a lower recurrence risk(OR=0.450).The constructed Nomogram prediction model demonstrated excellent performance:Validation results showed an AUC=0.842(95%CI:0.806～0.875),indicating outstanding discriminative ability.Conclusions This study successfully constructed and validated a Nomogram prediction model for osteosarcoma recurrence risk integrating key clinical factors.The model demonstrates superior discriminative ability and can accurately and quantitatively assess the recurrence risk for individual patients.This tool thus provides critical reference for guiding clinical treatment decisions.

To analyze the clinical data of patients with recurrent Clostridioides difficile infection(rCDI)in the southwestern region,and help clinicians identify high-risk populations early and adopt appropriate treatment strate-gies.Methods Clinical data of rCDI cases from a tertiary first-class hospital in southwest China from July 2019 to June 2024 were collected,and their host-related risk factors,exogenous risk factors,treatment schemes,and end-point outcomes were analyzed.Results In the past five years,a total of 26 cases of rCDI were detected from a ter-tiary first-class hospital in southwest China,accounting for 4.04％of the total positive cases(n=643)detected during the same period.19.23％of the recurrent patients experienced a second recurrence.The median age of rCDI patients was 66.5 years old,with males accounting for 73.08％.The major comorbidity included diabetes mellitus(34.62％),malignant tumors(30.77％),and chronic renal diseases(23.08％).In the 8 weeks before the first on-set of rCDI in patients,the top three drugs used were β-lactam and enzyme inhibitor compound(69.23％),proton pump inhibitors(65.38％),and carbapenems(46.15％).In the initial treatment of recurrent patients,3.85％(1/26)of the cases were treated with metronidazole,19.23％(5/26)of the cases received non-standard vancomy-cin/norvancomycin treatment in usage or dosage,46.15％(12/26)of the cases received treatment with course less than 10 days.In the treatment of the first recurrence,34.78％(8/26)of the cases received treatment with course less than 10 days.Conclusion For elderly patients and patients with diabetes mellitus,malignant tumors,and chronic renal diseases,who have used β-lactam and enzyme inhibitor compound,proton pump inhibitors,carbapene-ms within 8 weeks before disease onset,standard dose and treatment course of vancomycin or norvancomycin are recommended under permitted conditions,so as to reduce the risk of recurrence.

Acute ischemic stroke(AIS)is associated with high mortality and disability rates,presenting a substantial challenge to global public health challenge.Intravenous thrombolysis(IVT)is recognized as a cornerstone of early AIS treatment and is recommended as the standard therapeutic approach by both national and international guidelines.However,the clinical efficacy of IVT remains suboptimal due to several limitations,including a narrow therapeutic time window and the inevitable activation of the coagulation system and platelet aggregagation during thrombolysis.These factors may contribute to adverse outcomes such as early neurological deterioration(END)and vascular re-occlusion.Antiplatelet therapy(APT),which inhibits platelet aggregations,reduces microthrombus formation,and stabilizes the vascular endothelium with multifaceted mechanisms,has emerged as a promising adjunctive strategy to IVT,offering potential synergistic effects.This review summarized the latest evidence from both domestic and international studies,focusing on the mechanisms of APT,recent clinical advancements in IVT combined with APT,and the safety and efficacy of APT administration at different time windows relative to IVT.Emphasis is placed on the influence of various antiplatelet agents,dosing regimens,and initiation timing on therapeutic outcomes,alongside a comprehensive evaluation in the context of current guideline recommendations and clinical practice.Current guidelines recommend initiating APT 24 h after IVT,following imaging confirmation to exclude the risk of intracranial hemorrhage.However,the efficacy and safety of earlier APT initiation remain inconclusive.Individualized treatment strategies,such as early administration of low-dose,short-acting APT or combination therapy in specific patient subgroups,may effectively balance therapeutic benefits and risks.The adjunctive use of APT in IVT holds promise for enhancing efficacy and improving clinical outcomes,but precise stratification of safety and efficacy is essential.Future research should focus on optimizing combination IVT and APT strategies through individualized patient profiling,appropriate drug selection,and dynamic imaging monitoring to achieve precision management in AIS treatment.

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.