Objective To investigate the mechanism of action of biochanin A(BCA)on osteoarthritis through in vitro experiments.Methods Primary rat chondrocytes were extracted and cultured,and then divided into the control group(without inducer or interferant),the model group[10 ng/mL interleukin-1 β(IL-1 β)induction],and the BCA group(10 ng/mL IL-1β induction+0,3,6,12,24,48 μmol/L BCA intervention).Cell activity was detected by methyl thiazolyl tetrazolium(MTT)method.Senescence-associated β-galactosidase(SA-β-gal)staining was used to observe cell senescence.Intracellular inflammatory factors and oxidative stress indexes were detected by enzyme-linked immunosorbent assay(ELISA),the levels of related proteins were detected by Western blot,and the affinity between BCA and Nrf2 was verified by molecular docking technology.Results After screening the concentration of BCA with MTT,6,12 and 24 μmol/L BCA were selected for subsequent experiments.Compared with the control group,the chondrocyte activity and the activities of catalase(CAT)and superoxide dismutase(SOD)in the model group were significantly decreased(P＜0.05).The number of SA-β-gal positive cells and expres-sion levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and malondialdehyde(MDA)increased significantly(P＜0.05).The expression levels of type Ⅱ collagen(COL2A1)and aggrecan(ACAN)were significantly decreased(P＜0.05).Compared with the model group,the above conditions were significantly reversed in the BCA group(P＜0.05).In addition,BCA could significantly reduce the degrada-tion of inhibitor kappa B alpha(IκB-α)and nuclear translocation of NF-KBp65,and promote the expression of Nrf2 in the nucleus and the expression of human heme oxygenase-1(HO-1)in whole cells(P＜0.05).The results of molecular docking further confirmed that BCA had the highest affinity with Nrf2.Conclusion BCA can inhibit oxidative stress and inflammation of osteoarthritis chondrocytes by regulating Nrf2/NF-KB signaling pathway in vitro,and alleviate joint injury.

OBJECTIVES: To study the clinical and bronchoscopic characteristics of tracheobronchial tuberculosis (TBTB) in children and to identify factors influencing residual airway obstruction or stenosis. METHODS: The clinical data of children with TBTB were retrospectively collected. The children were divided into two groups based on the last bronchoscopic result within one year of follow-up: a group with residual airway obstruction or stenosis (n=34) and a group without residual airway obstruction or stenosis (n=58). A multivariate logistic regression analysis was used to identify the factors influencing residual airway obstruction or stenosis in children with TBTB. Receiver operating characteristic (ROC) curves were used to analyze the predictive value of the factors influencing residual airway obstruction or stenosis in children with TBTB. RESULTS: A total of 92 children with TBTB were included, and the main symptoms were cough (90%) and fever (68%). In children under 1 year old, the incidence rates of dyspnea and wheezing were significantly higher than in other age groups (P<0.008). Chest CT findings included mediastinal or hilar lymph node enlargement (90%) and tracheobronchial stenosis or obstruction (61%). The lymphatic fistula type was the main type of TBTB observed bronchoscopically (77%). All children received interventional treatment, and the effective rate was 84%. During one year of follow-up, 34 children had residual airway obstruction or stenosis. The TBTB diagnostic time and the initiation of interventional treatment were significantly delayed in the group with residual airway obstruction or stenosis compared with the group without residual airway obstruction or stenosis (P<0.05). The multivariate logistic regression analysis showed that the TBTB diagnostic time was closely related to residual airway obstruction or stenosis in children (P<0.05). ROC curve analysis showed that at the cut-off value of 92 days of TBTB diagnostic time, the area under the curve for predicting residual airway obstruction or stenosis in children with TBTB was 0.707, with a sensitivity of 58.8% and a specificity of 75.9%. CONCLUSIONS The clinical manifestations of TBTB are nonspecific, and symptoms are more severe in children under 1 year old. TBTB should be suspected in children with tuberculosis and chest imaging indicating airway involvement. Delayed diagnosis of TBTB is associated with the development of residual airway obstruction or stenosis.
Infant ; Child ; Humans ; Bronchoscopy/methods* ; Constriction, Pathologic/complications* ; Bronchial Diseases/therapy* ; Retrospective Studies ; Tuberculosis/diagnosis* ; Airway Obstruction/therapy*

OBJECTIVE This study aims to elucidate the mechanism of action of Isoliquiritigenin(ILG)in the treatment of Dia-betic Encephalopathy(DE)based on network pharmacological analysis and in-vitro experiments.METHODS The potential targets of ILG were predicted using the HERB database and SwissTargetPrediction database.DE-associated disease targets were obtained from GeneCards,OMIM,and PharmGkb,and the intersecting targets between ILG and DE were identified using the Venny software.A PPI network was constructed using the STRING database,and core targets were screened out using Cytoscape software.GO function and KEGG pathway enrichment analyses were undertaken using R 4.0.3,followed by validation via molecular docking techniques and in vitro experiments.RESULTS 65 intersecting targets between ILG and DE were identified in this study.Topological analysis yielded eight core targets namely,EGFR,ESR1,PTGS2,PPARG,GSK3β,CDK2,PIK3R1,and F3.GO function and KEGG pathway en-richment analyses revealed that ILG antagonizes DE through several biological processes which impact numerous cellular components and molecular functions such as response to lipopolysaccharides,protein phosphorylation,protein kinase activity,and serine/threo-nine/tyrosine kinase activity.Pathways implicated included the PI3K-Akt signaling pathway,protein polysaccharide signaling pathway in cancer,and endocrine resistance pathway.The molecular docking results showed that all eight core targets had a good binding with ILG,especially with GSK3β,with a binding energy of-7.22 kcal·mol-1.In vitro experiments indicated that ILG could improve high glucose-induced cell damage and activate the PI3K/AKT/GSK3β signaling pathway.CONCLUSION ILG is likely to exert its effects on GSK3β to regulate the PI3K/AKT/GSK3β signaling pathway,thereby alleviating DE.

Objective: To investigate the prognostic factors of children with congenital heart disease (CHD) who had undergone cardiopulmonary resuscitation (CPR) in pediatric intensive care unit (PICU) in China. Methods: From November 2017 to October 2018, this retrospective multi-center study was conducted in 11 hospitals in China. It contained data from 281 cases who had undergone CPR and all of the subjects were divided into CHD group and non-CHD group. The general condition, duration of CPR, epinephrine doses during resuscitation, recovery of spontaneous circulation (ROSC), discharge survival rate and pediatric cerebral performance category in viable children at discharge were compared. According to whether malignant arrhythmia is the direct cause of cardiopulmonary arrest or not, children in CHD and non-CHD groups were divided into 2 subgroups: arrhythmia and non-arrhythmia, and the ROSC and survival rate to discharge were compared. Data in both groups were analyzed by t-test, chi-square analysis or ANOVA, and logistic regression were used to analyze the prognostic factors for ROSC and survival to discharge after cardiac arrest (CA). Results: The incidence of CA in PICU was 3.2% (372/11 588), and the implementation rate of CPR was 75.5% (281/372). There were 144 males and 137 females with median age of 32.8 (5.6, 42.7) months in all 281 CPA cases who received CPR. CHD group had 56 cases while non-CHD had 225 cases, with the percentage of 19.9% (56/281) and 80.1% (225/281) respectively. The proportion of female in CHD group was 60.7% (34/56) which was higher than that in non-CHD group (45.8%, 103/225) (χ²=4.00, P=0.045). There were no differences in ROSC and rate of survival to discharge between the two groups (P>0.05). The ROSC rate of children with arthythmid in CHD group was 70.0% (28/40), higher than 6/16 for non-arrhythmic children (χ²=5.06, P=0.024). At discharge, the pediatric cerebral performance category scores (1-3 scores) of CHD and non-CHD child were 50.9% (26/51) and 44.9% (92/205) respectively. Logistic regression analysis indicated that the independent prognostic factors of ROSC and survival to discharge in children with CHD were CPR duration (odds ratio (OR)=0.95, 0.97; 95%CI: 0.92~0.97, 0.95~0.99; both P<0.05) and epinephrine dosage (OR=0.87 and 0.79, 95%CI: 0.76-1.00 and 0.69-0.89, respectively; both P<0.05). Conclusions: There is no difference between CHD and non-CHD children in ROSC and survival rate of survival to discharge was low. The epinephrine dosage and the duration of CPR are related to the ROSC and survival to discharge of children with CHD.
Cardiopulmonary Resuscitation ; Child ; Child, Preschool ; Female ; Heart Arrest/therapy* ; Heart Defects, Congenital/therapy* ; Humans ; Intensive Care Units, Pediatric ; Male ; Retrospective Studies

Objective: To investigate the relationship between body mass index (BMI) and sexual development in Chinese children. Methods: A nationwide multicenter and population-based large cross-sectional study was conducted in 13 provinces, autonomous regions and municipalities of China from January 2017 to December 2018. Data on sex, age, height, weight were collected, BMI was calculated and sexual characteristics were analyzed. The subjects were divided into four groups based on age, including ages 3-<6 years, 6-<10 years, 10-<15 years and 15-<18 years. Multiple Logistic regression models were used for evaluating the associations of BMI with sexual development in children. Dichotomous Logistic regression was used to compare the differences in the distribution of early and non-early puberty among normal weight, overweight and obese groups. Curves were drawn to analyze the relationship between the percentage of early puberty and BMI distribution in girls and boys at different Tanner stages. Results: A total of 208 179 healthy children (96 471 girls and 111 708 boys) were enrolled in this study. The OR values of B2, B3 and B4+ in overweight girls were 1.72 (95%CI: 1.56-1.89), 3.19 (95%CI: 2.86-3.57), 7.14 (95%CI: 6.33-8.05) and in obese girls were 2.05 (95%CI: 1.88-2.24), 4.98 (95%CI: 4.49-5.53), 11.21 (95%CI: 9.98-12.59), respectively; while the OR values of G2, G3, G4+ in overweight boys were 1.27 (95%CI: 1.17-1.38), 1.52 (95%CI: 1.36-1.70), 1.88 (95%CI: 1.66-2.14) and in obese boys were 1.27 (95%CI: 1.17-1.37), 1.59 (95%CI: 1.43-1.78), and 1.93 (95%CI: 1.70-2.18) (compared with normal weight Tanner 1 group,all P<0.01). Analysis in different age groups found that OR values of obese girls at B2 stage and boys at G2 stage were 2.02 (95%CI: 1.06-3.86) and 2.32 (95%CI:1.05-5.12) in preschool children aged 3-<6 years, respectively (both P<0.05). And in the age group of 6-10 years, overweight girls had a 5.45-fold risk and obese girls had a 12.54-fold risk of B3 stage compared to girls with normal BMI. Compared with normal weight children, the risk of early puberty was 2.67 times higher in overweight girls, 3.63 times higher in obese girls, and 1.22 times higher in overweight boys, 1.35 times higher in obese boys (all P<0.01). Among the children at each Tanner stages, the percentage of early puberty increased with the increase of BMI, from 5.7% (80/1 397), 16.1% (48/299), 13.8% (27/195) to 25.7% (198/769), 65.1% (209/321), 65.4% (157/240) in girls aged 8-<9, 10-<11 and 11-<12 years, and 6.6% (34/513), 18.7% (51/273), 21.6% (57/264) to 13.3% (96/722), 46.4% (140/302), 47.5% (105/221) in boys aged 9-<10, 12-<13 and 13-<14 years, respectively. Conclusions: BMI is positively correlated with sexual development in both Chinese boys and girls, and the correlation is stronger in girls. Obesity is a risk factor for precocious puberty in preschool children aged 3-<6 years, and 6-<10 years of age is a high risk period for early development in obese girls.
Adolescent ; Body Mass Index ; Child ; Child, Preschool ; China/epidemiology* ; Cross-Sectional Studies ; Female ; Humans ; Male ; Obesity/epidemiology* ; Overweight/epidemiology* ; Puberty ; Puberty, Precocious ; Sexual Development

OBJECTIVES: To investigate the distribution of body mass index (BMI) and risk factors for obesity in children with Diamond-Blackfan Anemia (DBA). METHODS: The children with DBA who attended National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, from January 2003 to December 2020 were enrolled as subjects. The related clinical data and treatment regimens were recorded. The height and weight data measured within 1 week before or after follow-up time points were collected to calculate BMI. The risk factors for obesity were determined by multivariate regression analysis in children with DBA. RESULTS: A total of 129 children with DBA were enrolled, among whom there were 80 boys (62.0%) and 49 girls (38.0%), with a median age of 49 months (range 3-189 months). The prevalence rate of obesity was 14.7% (19/129). The multivariate logistic regression analysis showed that the absence of ribosomal protein gene mutation was closely associated with obesity in children with DBA (adjusted OR=3.63, 95%CI: 1.16-11.38, adjusted P=0.027). In children with glucocorticoid-dependent DBA, obesity was not associated with age of initiation of glucocorticoid therapy, duration of glucocorticoid therapy, and maintenance dose of glucocorticoids (P>0.05). CONCLUSIONS There is a high prevalence rate of obesity in children with DBA, and the absence of ribosomal protein gene mutation is closely associated with obesity in children with DBA.
Child ; Male ; Female ; Humans ; Anemia, Diamond-Blackfan/genetics* ; Pediatric Obesity/complications* ; Glucocorticoids/therapeutic use* ; Prevalence ; Risk Factors ; Ribosomal Proteins/genetics* ; Mutation

Network pharmacological approaches were used to predict the components, targets and pathways of Erhuang decoction (EhD) in the treatment of acute lung injury (ALI). The SwissTargetPrediction platform, DisGeNET, Therapeutic Target Database (TTD), GeneCards and Online Mendelian Inheritance in Man (OMIM) databases were used to predict potential targets of EhD and were integrated with the predicted targets for the treatment of ALI. A protein-protein interaction network model was constructed by using String database and Cytoscape software; the DAVID platform was used for Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. A network of drug components-targets-pathways was constructed by Cytoscape software and the SwissDock platform was used to dock the molecules of EhD found in blood with the key disease targets. An ALI model was established in mice and inflammatory factor detection and Western blot protein expression experiments with lung tissue sections were carried out to verify the effect of EhD in the treatment of ALI. Animal experiment ethical requirements were approved by the Ethical Committee Experimental Animal Center of Shandong University (Grant Number: 2016020). We identified 148 potential targets including signal transducer and activator of transcription 3 (STAT3), vascular endothelial cell growth factor A (VEGFA), RAC-alpha serine/threonine-protein kinase (AKT1), and nuclear factor-kappa B/p65 (RELA). The potential targets are largely associated with the biological processes of inflammation, oxidative stress, and apoptosis. Additional pathways relate to cancer, VEGF signaling, mitogen-activated protein kinase (MAPK) signaling, and Toll-like receptors (TLRs) signaling, along with other signaling pathways. Pharmacodynamic experiments showed that EhD could significantly reduce the content of inflammatory factors and the degree of lung injury of ALI mice. Western blot revealed that EhD could significantly decrease the expression of NF-κB/p65 and upregulate the expression of NF-kappa-B inhibitor alpha (IκBα). From the perspective of network pharmacology, the mechanisms of EhD in the treatment of ALI is consistent with the characteristics of multiple ingredients, multiple targets and multiple pathways. This research provides a reference for further study of the mechanism of this traditional Chinese medicine.

Crassostrea sikamea (C.sikamea) is an important edible and medicinal seafood in China. In the present study, a compound named flazin was separated and identified from the ethyl acetate extract of C.sikamea (EAECs) for the first time. In addition, the 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetra zolium (MTS) assay revealed that EAECs and flazin inhibited the transformation of splenic lymphocytes in vitro. Moreover, flazin (20 μg·mL
Animals ; Carbolines ; Crassostrea ; Furans ; Lymphocytes ; Rats ; Rats, Sprague-Dawley ; Spleen

Objective:To explore systematic implementation of World Health Organization Family International Classifications (WHO-FICs) in the field of rehabilitation: the theoretical and policy framework at macro level, governance and management mechanism at meso level, and implementation modules at micro levels, respectively. Methods:The policy and theoretical framework of rehabilitation development was discussed based on the international rehabilitation policy documents of WHO, mainly as World Report on Disability, Global Action Plan on Disability and Rehabilitation in Health Service System. Protocol and roadmap of systematic implementation of WHO-FICs, including International Classification of Diseases (ICD-11), International Classification of Functioning, Disability and Health (ICF), and International Classification of Health Intervention (ICHIβ-2) was proposed. Results:With the use of WHO-FICs, the theoretical and policy framework of rehabilitation was constructed, and the contents and principles of modern rehabilitation services were clarified at macro-level. Rehabilitation is an important part of health service, there are six building blocks: i.e. leadership and governance, financing, human resources for health, service providing, medical technology and health information system. It proposed to use knowledge management system of WHO-FICs, including the classification, nomenclature, definitions, descriptions, terminology and coding systems, to standardize rehabilitation evaluation and statistics. The management and governance system of rehabilitation should be implemented using WHO-FICs. Rehabilitation services are based on the bio-psycho-social model and implemented the principles of people-centered and functioning-oriented. The systematic implementation of WHO-FICs in rehabilitation abide by the model of "Evaluation (ICHI)－Evaluation, Description, Classification and Coding of Functioning (ICF)－Disease Classification, Diagnosis and Coding (ICD)－Rehabilitation Intervention (ICHI)", and with the standardized process of "Evaluation (Functioning and unmet needs)－Diagnose (Disease and Functioning)－Planning of Rehabilitation－Intervention－Evaluation of Outcome". The mic-modules of implementation of WHO-FICs in rehabilitation had been constructed. There were 28 categories of diseases, 7 categories of functioning and 6 categories of rehabilitation interventions in rehabilitation proposed by International Society of Physical and Rehabilitation Medicine. According to ICD-11 and ICF, it proposed to use WHO Disability Assessment Schedule 2.0 (WHODAS 2.0), Brief Model Disability Survey (MDS-B) and VB40 Generic Functioning Domains (VB40), and the ICF core-sets in evaluation of functioning and rehabilitation outcome. The implementation of WHO-FICs in management of medical records and reporting realized the standardized management of medical record, encoding of diseases, functioning and intervention, reporting of performance, and provided tools for billing, reimbursement and payment management of rehabilitation. It proposed to develop WHO-FICs based clinical data sets and big data to implement functioning-related Diagnosis Related Groups and case-mix statistics. Conclusion:With the systematic implementation of WHO-FICs in rehabilitation, the policy and theoretical framework at macro level had been developed. The mechanism of management and governance at meso level had been explored. The application modules and approaches at micro level had been established. A scientific and effective overall solution had been proposed to enhance the scientific, standardized, refined and informatization level, strengthen the level and governance capacity, and improve the quality, safety and the coverage of rehabilitation services.

This paper explored the background, framework and approach, contents and implementation of WHO Rehabilitation in Health System using approaches of ICF and WHO Handbook for Guideline Development. The actions and significances of implementations of seven recommendations and one good practice statements on assistive products had been discussed.