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 compare the effects of the China Children's Asthma Action Plan (CCAAP)-based remote joint management model with traditional management model on the control of childhood asthma. Methods: A retrospective cohort study was conducted to analyze the general data and asthma control assessment data of 219 children with asthma who attended the respiratory department of Guangzhou Women's and Children's Medical Center from April 2021 to October 2021 and were followed up for 1 year or more. According to the follow-up management model, the CCAAP-based remote joint management model was used in the observation group and the traditional management model was used in the control group, and the propensity score matching method was applied to match the data of children in the two management models for comparison. Paired-samples t-test, Wilcoxon signed-rank test, McNemar χ²-test or χ²-test or nonparametric tests were used to compare the general data and asthma control assessment data between the two matched groups of children. Results: Among 219 children with asthma, 145 were male and 74 were female, aged at consultation (7.2±2.4) years. There were 147 cases in the observation group and 72 cases in the control group, and 27 cases in each of the observation and control groups were successfully matched. The number of asthma exacerbation aura, acute exacerbations, and emergency room visits or hospitalizations for asthma exacerbations were lower in the observation group than in the control group after pairing (1 (0, 2) vs. 3 (1, 5) times, 0 (0,0) vs. 0 (0, 1) times, 0 (0,0) vs. 1 (0, 1) times, Z=-3.42, -2.58, -3.17, all P<0.05). The use of peak flowmeters was higher in children aged 5 years and older in the observation group than in the control group after pairing (100% (22/22) vs. 13% (3/23), χ²=54.00,P<0.001). The ratio of actual to predicted 1st second expiratory volume of force after follow-up in the observation group after pairing was higher than that before follow-up in the observation group and after follow-up in the control group ((95±11)% vs. (85±10)%, (95±11)% vs. (88±11)%, t=-3.40, 2.25, all P<0.05). The rate of complete asthma control after follow-up was higher in both the observation and control groups after pairing than before follow-up for 12 months in both groups (93% (25/27) vs. 41% (11/27), 52% (14/27) vs. 41% (11/27), H=56.19, 45.37, both P<0.001), and the rate of complete control of asthma in children in the observation group was higher than that in the control group at 3 and 12 months of follow-up management (56% (15/27) vs. 25% (5/20), 93% (25/27) vs. 52% (14/27), χ²=47.00, 54.00, both P<0.001). The number of offline follow-up visits, inhaled hormone medication adherence scores, and caregiver's asthma perception questionnaire scores were higher in the observation group than in the control group after pairing (6 (4, 8) vs. 4 (2,5), (4.8±0.3) vs. (4.0±0.6) score, (19.3±2.6) vs. (15.2±2.7) score, Z=6.58, t=6.57, 5.61, all P<0.05), and the children in the observation group had lower school absences, caregiver absences, asthma attack visit costs, and caregiver PTSD scores than the control group (0 (0,0) vs.3 (0, 15) d, 0 (0,0) vs. 3 (0, 10) d, 1 100 (0, 3 700) vs. 5 000 (1 000, 10 000) yuan, 1.3 (1.1, 1.9) vs. 2.0 (1.2, 2.7) score, Z=-2.89, -2.30, 2.74, 2.73, all P<0.05). Conclusion: The CCAAP-based joint management model of asthma control is superior to the traditional management model in the following aspects: it can effectively improve asthma control, self-monitoring, and lung function in children; it can improve treatment adherence and caregivers' asthma awareness; and it can reduce the duration of absenteeism from school, the cost of asthma exacerbation visits, and caregiver's negative psychology.
Humans ; Child ; Female ; Male ; Retrospective Studies ; Asthma/therapy* ; China ; Hospitalization ; Hospitals

Aim To explore he preventive and therapeutic effects of Tongbu-fangchan prescription on aceylcholine-calcium chloride (Ach-CaCl

Humans ; Lymphoma, Large B-Cell, Diffuse/genetics* ; Herpesvirus 4, Human/genetics* ; Mutation ; Epstein-Barr Virus Infections/pathology* ; Hepatitis A Virus Cellular Receptor 2/genetics*

Objective: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. Methods: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. Results: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). Conclusion An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.
Aged ; Asian Continental Ancestry Group ; Blood Glucose/analysis* ; China/epidemiology* ; Cohort Studies ; Diabetes Mellitus/blood* ; Female ; Glucose Tolerance Test ; Glycated Hemoglobin A/analysis* ; Glycemic Index ; Humans ; Male ; Middle Aged ; Uric Acid/blood*

OBJECTIVE: To study the clinical features and recurrence factors of myelin oligodendrocyte glycoprotein (MOG) antibody disease in children and the effect of recurrence prevention regimens. METHODS: A retrospective analysis was performed on the medical data of 41 children with MOG antibody disease who were hospitalized in the Department of Pediatric Neurology, Xiangya Hospital of Central South University, from December 2014 to September 2020. According to the presence or absence of recurrence, they were divided into a monophasic course group ( RESULTS: For these 41 children, acute disseminated encephalomyelitis was the most common initial manifestation and was observed in 23 children (56%). Of the 41 children, 22 (54%) experienced recurrence, with 57 recurrence events in total, among which optic neuritis was the most common event (17/57, 30%). The proportion of children in the recurrence group who were treated with corticosteroids for less than 3 months in the acute phase was higher than that in the monophasic course group (64% CONCLUSIONS More than half of the children with MOG antibody disease may experience recurrence. Most children with recurrence are treated with corticosteroids for less than 3 months in the acute phase. Rituximab and azathioprine may reduce the risk of recurrence.
Autoantibodies ; Child ; Humans ; Myelin-Oligodendrocyte Glycoprotein ; Optic Neuritis ; Recurrence ; Retrospective Studies

A case of 3-hydroxyisobutyryl-CoA hydrolase deficiency was reported, and its clinical features, gene mutation characteristics, and diagnosis and treatment were analyzed with reference to related literature. The patient aged 1 year and 6 months had developmental regression and paroxysmal dystonia after pyrexia and diarrhea, and head MRI showed symmetrical lesions in the bilateral basal ganglia. No pathogenic mutation was found in the full-length detection of mitochondrial genome. Nuclear gene detection of mitochondrial-related diseases found new compound heterozygous mutations in the HIBCH gene, i.e., c.439-2A>G and c.958A>G (p.K320E), which were inherited from his father and mother, respectively. The boy was given cocktail therapy, dietary valine restriction, and symptomatic treatment. After 2 weeks of treatment, there were improvements in dystonia and motor and intellectual development.

Objective To analyze the present situation and reasons of short-term unplanned extubation after peripherally inserted central venous catheters (PICC)surgery in cancer patients. Methods A total of 2 458 cancer patients underwent PICC surgery were collected,and patients experienced short-term unplanned extubation were screened out to analyze the general information, catheter situation and reasons of unplanned extubation.Results Totally 2 431 cases (98.90%, 2431 /2458)were successfully followed-up and 103 patients (4.24%,103 /2431)experienced short-term unplanned extubation.Among them,the proportion of patients received primary PICC,pa-tients over 65 years old and patients with catheter located in median cubital vein were 96.12%(99 /103),59.22% (61 /103)and 46.60% (48 /103)respectively.The incidence of unplanned extubation were related to age,vascular choose and whether the primary PICC.Subjective will (61.17%,63 /103)of patients was the main reason for short-term unplanned extubation and the objective reasons were catheter prolapse (10.67%,11 /103),local thrombosis (7.77%,8 /103) and puncture site exudation /phlebitis(6.80%,7 /103),catheter-related infections (5.83%,6 /103)and so on.Conclusion Effective maintenance during the entire process after PICC such as adequate doctor-patient communication,positive patient education,strengthening outside hospital PICC maintenance training as well as establishment of good follow up system can reduce the inci-dence rate of short-term unplanned extubation.

ABSTRACT:Objective To explore the correlation between the psychological resilience and quality of life in breast cancer patients with chemotherapy.Methods From January 2012 through December 2013,80 breast cancer patients with adjuvant hormonal therapy were selected as object. The psychological resilience was assessed by Conner-Davidson Resilience Scale and the quality of life was assessed by Functional Assessment of Cancer Therapy-Breast (FACT-B)at 1 month and 6 months after chemotherapy.The correlation between the psychological resilience and quality of life was assessed by Spearman correlation analysis.Results The total scores of psychological re-silience in breast cancer chemotherapy patients at 1 month and 6 months after chemotherapy were (45.72±8.44)and (49.35±8.27),which were significantly lower than (65.4±13.9)of the do-mestic norm (P <0.05).The scores of tenacity,self reliance and optimism in breast cancer chemotherapy patients were also lower than those of the domestic norm (P <0.05).Spearman correlation analysis showed that the psychological resilience had positive correlations with physical dimension,social /family dimension,emotional dimension and functional dimension (P <0.05). Conclusion Psychological resilience in breast cancer chemotherapy patients is low,and it shows a positive correlation with quality of life.The strength of the resilience in breast cancer chemothera-py patients can help promote their quality of life.

Objective To analyze the present situation and reasons of short-term unplanned extubation after peripherally inserted central venous catheters (PICC)surgery in cancer patients. Methods A total of 2 458 cancer patients underwent PICC surgery were collected,and patients experienced short-term unplanned extubation were screened out to analyze the general information, catheter situation and reasons of unplanned extubation.Results Totally 2 431 cases (98.90%, 2431 /2458)were successfully followed-up and 103 patients (4.24%,103 /2431)experienced short-term unplanned extubation.Among them,the proportion of patients received primary PICC,pa-tients over 65 years old and patients with catheter located in median cubital vein were 96.12%(99 /103),59.22% (61 /103)and 46.60% (48 /103)respectively.The incidence of unplanned extubation were related to age,vascular choose and whether the primary PICC.Subjective will (61.17%,63 /103)of patients was the main reason for short-term unplanned extubation and the objective reasons were catheter prolapse (10.67%,11 /103),local thrombosis (7.77%,8 /103) and puncture site exudation /phlebitis(6.80%,7 /103),catheter-related infections (5.83%,6 /103)and so on.Conclusion Effective maintenance during the entire process after PICC such as adequate doctor-patient communication,positive patient education,strengthening outside hospital PICC maintenance training as well as establishment of good follow up system can reduce the inci-dence rate of short-term unplanned extubation.