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 verify the effect of Fu′s massage combined with physical therapy technology in rapidly relieving neck and low back pain caused by long-haul flight.Methods:Forty-two male volunteers were divided into 8, 12, 16, 24 and 48 h groups according to the simulated flying hours. After the completion of the simulated long-haul flight, the 5 groups of volunteers were immediately treated with Fu′s massage combined with physical factors for neck and low back pain. The Visual Analogue Scale (VAS) was used to evaluate the cervical and lumbar pain of volunteers after simulated flight and after treatment, and the treatment effect was before treatment analyzed.Results:There were significant differences in the VAS scores of cervical and lumbar regions before treatment among volunteers with different flying hours ( H=-30.15, -28.25, both P<0.001). The VAS scores of cervical and lumbar regions of volunteers in the 24 h and 48 h groups were higher than those in the 8 h group ( P=0.002, <0.001, =0.002, <0.001). The VAS scores of cervical and lumbar regions of volunteers in the 48 h group were higher than those in the 12 h group ( P=0.016, 0.001). The VAS score of cervical region of volunteers in the 48 h group was higher than that in the 16 h group ( P=0.033). After the intervention of Fu's massage combined with physical therapy, the VAS scores of cervical and lumbar regions in each group were lower than those before treatment, and the differences were significant ( t/ Z=-3.00-17.00, all P<0.05 or 0.01). Conclusions:Fu′s massage manipulation combined with physical treatment can effectively relieve the neck and low back pain caused by long-haul flight, which can be widely used as a relief method.

Objective:To verify the effect of Fu′s massage combined with physical therapy technology in rapidly relieving neck and low back pain caused by long-haul flight.Methods:Forty-two male volunteers were divided into 8, 12, 16, 24 and 48 h groups according to the simulated flying hours. After the completion of the simulated long-haul flight, the 5 groups of volunteers were immediately treated with Fu′s massage combined with physical factors for neck and low back pain. The Visual Analogue Scale (VAS) was used to evaluate the cervical and lumbar pain of volunteers after simulated flight and after treatment, and the treatment effect was before treatment analyzed.Results:There were significant differences in the VAS scores of cervical and lumbar regions before treatment among volunteers with different flying hours ( H=-30.15, -28.25, both P<0.001). The VAS scores of cervical and lumbar regions of volunteers in the 24 h and 48 h groups were higher than those in the 8 h group ( P=0.002, <0.001, =0.002, <0.001). The VAS scores of cervical and lumbar regions of volunteers in the 48 h group were higher than those in the 12 h group ( P=0.016, 0.001). The VAS score of cervical region of volunteers in the 48 h group was higher than that in the 16 h group ( P=0.033). After the intervention of Fu's massage combined with physical therapy, the VAS scores of cervical and lumbar regions in each group were lower than those before treatment, and the differences were significant ( t/ Z=-3.00-17.00, all P<0.05 or 0.01). Conclusions:Fu′s massage manipulation combined with physical treatment can effectively relieve the neck and low back pain caused by long-haul flight, which can be widely used as a relief method.

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: 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

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 investigate the incidence and prognosis of tricuspid regurgitation after transcatheter closure of perimembranous ventricular septal defects in pediatric patients as well as the risk factors of regurgitation occurrence or aggravation. Methods: Clinical data of 1 108 patients who underwent percutaneous closure in Shanghai Children′s Medical Center, School of Medicine, Shanghai Jiaotong University from January 2011 to January 2017 was analyzed retrospectively, and the prognosis and risk factors of postoperative tricuspid regurgitation and aggravation were also analyzed. Results: Mild tricuspid regurgitation occurred in 24 cases after surgery with the incidence of 2.1%.Among 5 cases with mild or above preoperative tricuspid regurgitation, the regurgitation was alleviated after surgery in 4 cases.No severe tricuspid regurgitation requiring surgical intervention occurred in any patient during follow-up.Univariate analysis showed that intervention time (P<0.05) and residual shunt (P<0.05) were risk factors for mild or above tricuspid regurgitation after intervention.Binary regression analysis indicated that the size of the occluder (mm) (OR=1.48, 95%CI: 1.13-1.90) and residual shunt (OR=6.53, 95%CI: 1.69-25.30) were risk factors for tricuspid regurgitation after intervention (all P<0.05). Conclusions There is a certain incidence of tricuspid regurgitation after transcatheter closure of perimembranous ventricular septal defects, but most tricuspid regurgitation do not need surgical intervention.The intervention time, size of occluder and residual shunt are risk factors of intraoperatively or postoperatively tricuspid regurgitation.

Objective:To explore the expression and significance in regulating immune balance of programmed cell death protein 1 (PD-1) and its ligands PD-L1, PD-L2 in allergic rhinitis (AR).Methods:Eighty-two patients who received outpatient treatment due to high nasal reaction symptoms or were hospitalized due to nasal septum deviation and underwent nasal septum correction surgery in Department of Otorhinolaryngology Head and Neck Surgery of Renmin Hospital of Wuhan University from May 2018 to May 2019 were enrolled, including 42 males and 40 females, with the age ranging from 14 to 38 years old. Blood, inferior turbinate nasal mucosal tissue and relevant clinical data were collected. Patients were divided into AR group and control group due to clinical manifestation, skin prick test and detection of specific IgE (sIgE) in serum. Immunohistochemistry was used to detect the expression of PD-1 and its ligands in nasal mucosa of the two groups. Flow cytometry was used to detect the proportions of PD-1 +CD4 +T cells, PD-L1 + myeloid dendritic cells (mDCs), PD-L2 +mDCs and Th2 cells in peripheral blood of the two groups. The expression levels of total IgE, sPD-1, sPD-L1 and sPD-L2 in serum of the two groups were detected by ELISA. The measurement data of normal distribution or normal distribution after the logarithm conversion to Ln were compared by t test. Pearson correlation or Spearman correlation was used to analyze the correlation among the indicators. P<0.05 was considered statistically significant. Results:The expression of PD-1 and its ligands on the surface of immune cells in the nasal mucosa of the AR group was significantly higher than that of the control group. The ratio of PD-1 +CD4 +T cells, PD-L1 +mDCs and Th2 cells in peripheral blood of AR group was significantly higher than that of the control group ((15.24±6.45)% vs (8.71±5.33)%, (8.79±2.01)% vs (5.74±2.90)%, (7.89±1.95)% vs (2.52±1.34)%, all P<0.05). There was no significant difference in the ratio of PD-L2 +mDCs between the two groups. Correlation analysis found that the proportion of PD-1 +CD4 + T cells was positively correlated with the Visual Analogue Scale (VAS) score of AR, total IgE concentration and the serum sIgE concentration ( r value was 0.501, 0.541, 0.608, respectively, all P<0.05). The proportion of PD-L1 +mDCs was positively correlated with the VAS score of AR and the serum sIgE concentration ( r value was 0.604, 0.563, respectively, all P<0.05). The proportion of Th2 cells in peripheral blood was positively correlated with the proportion of PD-L1 +mDCs and PD-1 +CD4 +T cells ( r value was 0.538, 0.623, respectively, all P<0.05). Serum total IgE, sPD-1 and sPD-L1 in the AR group were significantly higher than those in the control group ((6.34±1.38) ng/ml vs (4.89±1.10) ng/ml, (4.40±1.01) pg/ml vs (3.79±1.21) pg/ml, (3.88±0.25) pg/ml vs (3.57±0.23) pg/ml, all P<0.05), and there was no significant difference in sPD-L2 levels between the two groups. Correlation analysis showed that sPD-L1 was positively correlated with total IgE and sIgE concentration ( r values was 0.32, 0.45, respectively, all P<0.05). Conclusions:PD-1 and PD-L1 are highly expressed on the surface of immune cells in peripheral blood and nasal mucosa of AR patients, and sPD-1 and sPD-L1 expression levels in peripheral blood of AR patients are increased. The PD-1/PD-L1 signaling pathway promote AR inflammatory response by inducing Th2 type immune response.

Objective To investigate the distribution and drug resistance of carbapenem-resistant Enterobacteriaceae ( CRE) isolated from children in China. Methods CRE strains were collected in 10 ter-tiary children's hospitals of China from January 1, 2016 to December 31, 2017. Antimicrobial susceptibility of the clinical strains was detected with disk diffusion method ( KB method) and automated method. The re-sults were analyzed according to the Clinical and Laboratory Standards Institute ( CLSI) Standards published in 2017. WHONET 5. 6 software was used to retrospectively analyze the distribution characteristics and drug resistance of these strains. Results A total of 3065 CRE clinical strains were isolated from children with an overall prevalence of 7. 7％ and among them, 13. 5％ were isolated in neonatal group and 5. 8％ in non-neo-natal group. The detection rate of CRE in 2017 was higher than that in 2016 (9. 7％ vs 5. 7％). Among the 3065 CRE strains, there were 1912 strains of Klebsiella pneumoniae (62. 0％), 667 strains of Escherichia coli (22. 0％), 206 strains of Enterobacter cloacae (7. 0％), 56 strains of Klebsiella aerogenes (1. 8％) and 47 strains of Serratia marcescens (1. 5％). Most of the strains were isolate in neonatology departments including neonatal intensive care units (NICU) and intensive care units (ICU), accounting for 44. 8％ and 19. 7％, respectively. Respiratory tract (61. 8％), urine (19. 4％) and blood (5. 7％) specimens were the main sources of CRE isolates. Results of antimicrobial susceptibility test showed that the CRE strains were highly resistant to carbapenem antibiotics such as imipenem, meropenem and ertapenem, as well as penicillins and most cephalosporins (79. 6％-100％), especially those isolated in the neonatal group (P<0. 05). Children had relatively low resistance rates to aminoglycosides such as amikacin (19. 7％) and fos-fomycin (11. 9％), fluoroquinolones such as levofloxacin (37. 7％) and ciprofloxacin (43. 3％), and tige-cycline (3. 8％). Currently, no polymyxin B-resistant strains were isolated. Conclusions The prevalence of common CRE strains in children in 2017 was higher than that in 2016, especially in newborns. Drug re-sistance in CRE strains isolated from neonates to common antibiotics was more severe, suggesting that great attention should be paid to it and timely measures should also be taken.

OBJECTIVETo detect RAS mutations in the circulating cell-free DNA (cfDNA) in the plasma and explore the their correlation with the clinicopathological features in patients with colorectal cancer.

METHODSReal-time PCR was used to detect RAS mutations in plasma cfDNA and matched tumor tissue DNA samples from 71 colorectal cancer patients. The correlation of RAS mutations with the clinicopathological features of the patients were analyzed.

RESULTSOf the 71 patients with colorectal cancer, 23 (32.39%) showed RAS mutations in the cfDNA and 36 (50.7%) showed RAS mutations in tumor tissue DNA, with a concordance rate of 76.06% in the results between the two samples (Kappa=0.523). RAS mutations in the cfDNA were not related to the patients' age (P=0.072), gender (P=0.320), tumor stage (IVa and IVb, P=0.450), primary tumor position (P=0.324), lung metastasis (P=0.237), CEA level (P=0.284) or CA199 level (P=0.427). The positivity rate of RAS mutations in plasma cfDNA was significantly higher in patients with liver metastasis than those without liver metastasis (P=0.045).

CONCLUSIONPlasma cfDNA can be a reliable source of diagnostic DNA to replace the tumor tissue DNA for diagnosis of RAS mutations. RAS mutations in plasma cfDNA occur more frequently in colorectal cancer patients with liver metastasis.