Atrial fibroblast-derived exosomal miR-21 upregulate myocardial KCa3.1 via the PI3K-Akt pathway during rapid pacing.

Background: Fibroblast-derived exosomes can regulate the electrical remodeling of cardiomyocytes, and the intermediate-conductance calcium-activated potassium channel (KCa3.1) is important in atrial electrical remodeling. However, the underlying molecular mechanisms remain unclear. This study aimed to investigate the regulation of cardiac electrophysiology by exosomes linked to KCa3.1. Methods: Atrial myocytes (AMs) and atrial fibroblasts were isolated from Sprague-Dawley suckling rats and cultured individually. The cellular atrial fibrillation (AF) model was established via electrical stimulation (1.0 v/cm, 10 Hz), and fibroblast-derived exosomes were isolated via ultracentrifugation. Exosomes were co-cultured with AMs to investigate their influences on KCa3.1 and the underlying mechanisms. Nanoparticle tracking analysis and transmission electron microscopy were used to measure exosome particle sizes and concentrations. Whole-cell patch clamp was applied to record the current density of KCa3.1 and action potential duration (APD). The expression of miR-21-5p was detected by reverse-transcription polymerase chain reaction (RT-PCR). Western blotting or immunofluorescence was used to measure the expression of exosomal markers, Akt phosphorylation, and KCa3.1. Results: Rapid pacing promoted the secretion of exosomes from atrial fibroblasts and miR-21-5p expression in atrial fibroblasts and exosomes. KCa3.1 protein expression and current density significantly increased, and APD50 and APD90 were sharply shortened after rapid pacing in AMs. TRAM-34 (KCa3.1 blocker) extended APD and reduced susceptibility to AF. KCa3.1 and P-AKT expressions were amplified after co-culturing AMs with exosomes secreted by atrial fibroblasts. In contrast, the increase in KCa3.1 expression was reversed after the cells were co-cultured with exosomes secreted by atrial fibroblasts that were transfected with miR-21-5p inhibitors or after the use of LY294002, a PI3K/Akt pathway inhibitor. Conclusions: Rapid pacing promoted the secretion of exosomes from fibroblasts, and miR-21-5p was upregulated in exosomes. Moreover, the miR-21-5p-enriched exosomes upregulated KCa3.1 expression in AMs via the PI3K/Akt pathway.

Mediating role of burnout in relationship between psychological resilience and psychological distress among CDC staff during COVID-19 pandemic / 环境与职业医学

Background The staff in centers for disease control and prevention (CDC) were at a great risk for psychological distress when they were faced with outbreak-related prevention and control work and routine tasks during the COVID-19 period. Psychological resilience and burnout are two key influencing factors on psychological distress. Objective To explore the status and mechanisms of psychological resilience, burnout, and psychological distress among CDC staff. Methods From September to October 2022, a cross-sectional survey was conducted in all CDC staff in Beijing, and 2228 CDC staff from 17 units (including 1 municipality-level CDC and 16 district-level CDCs) participated the questionnaire survey. The basic information questionnaire, Connor-Davidson Resilience Scale (CD-RISC-10) Chinese version, Maslach Burnout Inventory-General Survey (MBI-GS) Chinese version, and the 10-item Kessler Psychological Distress Scale (Kessler10) Chinese version were selected in our study. Mann-Whitney U test or Kruskal-Wallis H test was used to analyze the differences in the scores of psychological resilience, burnout, and psychological distress by demographic and sociological characteristics. The correlations among the three elements were analyzed by Spearman correlation analysis. Potential influencing factors of psychological distress of the CDC staff were evaluated by multiple linear regression. A potential mediating effect of psychological resilience-burnout-psychological distress was analyzed by the mediation package of R 4.2.0, and validated by Bootstrap method. Results Of 2228 questionnaires distributed, 2022 valid questionnaires were collected, and the recovery rate was 90.75%. The median (P25, P75) psychological distress score of CDC staff was 13.00 (8.00, 24.00), and the number of participants with psychological distress levels of 1, 2, 3, and 4 was 358 (17.71%), 546 (27.00%), 362 (17.90%), and 756 (37.39%), respectively. The median (P25, P75) psychological resilience score was 24.00 (20.00, 30.00) and the median (P25, P75) burnout score was 38.00 (25.00, 50.00). The results of the multiple linear regression showed that psychological resilience, burnout, caring for the elderly, having a chronic disease, and monthly income had independent influences on psychological distress (P<0.05), and emotional exhaustion, cynicism, and reduced personal accomplishment (reversed) in the case of burnout had a great effect on psychological distress (P<0.05). After controlling general demographic characteristic variables, total burnout score exerted a partial mediation effect on the relationship between psychological resilience and psychological distress, with a mediation effect value of −0.439 (95%CI: −0.483, −0.397), and a total mediation effect contribution rate of 60.89%. The two dimensions of burnout (emotional exhaustion and cynicism) played a partial mediating role between psychological resilience and psychological distress, with mediating effect contribution rates of 42.44% and 41.41%, respectively. Conclusion Psychological distress among CDC staff in Beijing was prominent during COVID-19. Psychological resilience can act directly on psychological distress or indirectly on psychological distress through burnout. Both emotional exhaustion and cynicism dimensions of burnout have a partial mediating role between psychological resilience and psychological distress. Increasing psychological resilience and decreasing burnout may reduce the occurrence of psychological distress.

Relationship between polymorphism of Visfatin gene rs61330082,rs4730153 and type 2 diabetes mellitus / 中国糖尿病杂志

Objective To evaluate the value of rs61330082 and rs4730153 polymorphisms of Visfatin locus for the diagnosis of type 2 diabetes mellitus(T2DM)in a high-risk population.Methods SNPscanTM high-throughput single nucleotide polymorphism typing technique was used to genotype Visfatin gene loci rs61330082 and rs4730153 in 346 T2DM patients(T2DM group)and 1426 normal controls(NC group).Logistic regression analysis was used to analyze T2DM risk factors.ROC curves were used to analyze the optimal cut-off values of Visfatin gene rs61330082 and rs4730153 for the diagnosis of T2DM.Results The proportion of women,age,obesity,smoking,hypertension,FPG,HbA1c and TG were higher in T2DM group than those in NC group(P<0.01)and HDL-C was lower than in NC group(P<0.01).The frequency of G allele and GG genotype was higher in T2DM group compared with NC group(P<0.05).Logistic regression analysis showed that age,female,obesity,hypertension,TG,and GG genotype at rs4730153 locus were risk factors for T2DM,HDL-C was a protective factor for T2DM.The area under the ROC curve of GG genotype at Visfatin rs4730153 mutation for diagnosis of T2DM was 0.668 and the optimal cut-off point for predicting T2DM was 20.04%,with sensitivity 60.1%and specificity 66.1%,respectively.Conclusion The GG genotype of Visfatin gene rs4730153 locus is associated with the risk of T2DM and can beused as a candidate gene for predicting phenotype of T2DM.

Effect and Potential Mechanism of Inhibition of Long Non-coding RNA MALAT1 on Glycolipipotoxicity-induced Endothelial Cell Dysfunction / 中国循环杂志

Objectives:To investigate the effect of inhibition of long non-coding RNA(lnc RNA)in human metastasis associated lung adenocarcinoma transcript 1(MALAT1)on glycolipitoxicity-induced human umbilical vein endothelial cell dysfunction. Methods:Human umbilical vein endothelial cells were treated with glucose and palmitic acid in vitro to establish the glycolipitoxic endothelial cell models.Following groups were examined:control group,high-glucose and high-fat group,high-glucose and high-fat + non-targeting RAN control group,high-glucose and high-lipid+MALAT1 siRNA group,and high-glucose and high-lipid+MAPK1 siRNA group.RT-qPCR was used to detect the mRNA expression of MALAT1 and MAPK1.Western blot was used to detect the expression levels of autophagy,mitochondrial fusion division,apoptosis,and pathway-related proteins.Immunofluorescence confocal localization was used to detect the fluorescence colocalization of autophagy and lysosome-related proteins.The number of autophagolysosomes in endothelial cells was observed by transmission electron microscopy.Mitochondrial probe staining was used to detect mitochondrial morphology,immunofluorescence was used to detect intracellular reactive oxygen species(ROS)production,flow cytometry was used to detect the apoptosis of cells in each group,cell proliferation and scratch assays were used to detect the proliferation and migration ability of cells in different groups at different time points.The angiogenesis was quantified by counting the number of new blood vessels in each group. Results:Compared with the control group,the expression of lncRNA MALAT1 mRNA and the expression of phosphorylated mito-activated protein kinase 1(p-MAPK1)were upregulated(both P＜0.05)and the expression of phosphorylated mammalian target protein(p-mTOR)was downregulated in the high-glucose and high-fat group and the high-sugar and high-fat control group(all P＜0.01).Compared with the high-glucose and high-fat non-targeting RNA control group,the expressions of microtubule-associated protein 1A/1B-light chain 3(LC3)and p62 were downregulated(P＜0.01,P＜0.05),LC3 and lysosome-associated membrane protein 2(LAMP2)protein co-localized positive fluorescence particles were increased(both P＜0.01),number of lysosomes were decreased,the expression of ROS was decreased(P＜0.01),the expression level of mitochondrial fusion protein optic nerve atrophin 1(OPA1)was increased(P＜0.05),the expressions of cleaved caspase-3 and BCL-2-related X protein(BAX)were decreased and BCL-2 was increased(all P＜0.05),cell proliferation,migration,and tube-forming ability were increased(all P＜0.01),and the expression of p-MAPK1 was decreased(P＜0.05)and p-mTOR expression was increased(both P＜0.05)in the high-glucose and high-lipid+si-MALAT1 group.Compared with the high-glucose and high-fat non-targeting RNA control group,the expression of p-MAPK1 in endothelial cells was decreased and the expression of p-mTOR was increased in the high-glucose and high-lipid+si-MAPK1 group(both P＜0.01). Conclusions:Inhibition of lncRNA MALAT1 expression can reduce the level of mitophagy in glycolipidotoxic environments,reduce apoptosis of endothelial cells and improve endothelial cell function,which may be related to the regulation of MAPK1/mTOR signaling pathway.

Mechanism of Tripterygium wilfordii in treating renal cell carcinoma using network pharmacology / 国际生物医学工程杂志

Objective:To explore the mechanism of Tripterygium wilfordii in treating renal cell carcinoma using network pharmacology and experimental validation. Methods:The traditional Chinese medicine systems pharmacology (TCMSP) database and analysis platform was utilized to screen the active ingredients of T. wilfordii and predict the targets using the Swiss database. Renal cell carcinoma related targets were collected from DisGeNET, GeneCards, and OMIM databases, and intersecting targets were obtained through Venny 2.1.0. Protein-protein interaction (PPI) networks were mapped using the STRING database and Cytoscape software, and gene ontology (GO) and kyoto encyclopedia of genes and genomics (KEGG) enrichment analyses were performed. Component-target-pathway networks were constructed using Cytoscape software. To induce the subcutaneous transplantation tumor model of renal cell carcinoma, nude mice were randomly divided into a control group and a treatment group, with 5 mice in each group. In the treatment group, mice were gastrically instilled with 615 mg/ml of T. wilfordii solution (1 845 mg T. wilfordii granules dissolved into 3 ml water) 2.46 g/kg, 10 μl/time, once daily for 21 d. In the control group, mice were gastrically instilled with an equal amount of saline. Tumor volume was measured once every 5 days, and the expression of serine/threonine protein kinase 1 (AKT1), signal transduction and transcription activator 3 (STAT3), tumor necrosis factor (TNF), tumor protein p53 (TP53), JUN, mitogen-activated protein kinase 8 (MAPK8), and MAPK14 was detected by enzyme-linked immunoassay. Results:Twenty-eight active pharmaceutical ingredients and 117 potential targets of T. wilfordii were screened; 13 425 related disease targets were identified; and finally, 113 drug-disease intersecting targets were obtained. In the PPI network, AKT1, STAT3, TNF, TP53, JUN, MAPK8, and MAPK14 were the core targets. GO analysis showed that BP mainly included nuclear receptor activity, ligand-activated transcription factor activity, RNA polymerase-specific DNA-binding transcription factor binding, nuclear steroid receptor activity, and adrenergic receptor activity, etc. CC mainly included the response to hormones, the cellular response to lipids, the positive regulation of cell migration, the response to TNF, the inflammatory response, the cellular response to hormonal stimulation, the response to hypoxia, the response to metal ions, etc. MF involves membrane rafts, membrane microregions, the outer side of the plasma membrane, the lateral side of the membrane, plasma membrane rafts, presynaptic membranes, vesicles, transcriptional regulatory complexes, post-synaptic membranes, synaptic membranes, etc. KEGG analysis showed that T. wilfordii treatment of RCC involves signaling pathways such as lipid and atherosclerosis, advanced glycosylation end product-receptor for advanced glycosylation end products (AGE-RAGE), TNF, Toll-like receptor, phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt), and MAPK. The experimental validation results showed that the tumor volume was reduced after treatment with tretinoin ( P < 0.05), the expression of TP53 protein was increased ( P < 0.001), and the expression of AKT1, STAT3, TNF, JUN, MAPK8, and MAPK14 proteins were all reduced (all P < 0.001). Conclusions:In this study, the target and signaling pathways of T. wilfordii treatment of renal cell carcinoma were initially predicted, providing a reference basis for further research on its protective mechanism and clinical application.

Correlation analysis of serum anti-Mullerian hormone level and ovarian interstitial blood flow in patients with polycystic ovary syndrome / 中国医师进修杂志

Objective:To investigate the correlation between the level of anti Mullerian hormone (AMH) in serum and ovarian interstitial blood flow in patients with polycystic ovary syndrome (PCOS).Methods:The clinical data of 88 patients with PCOS (PCOS group) admitted to Jiangshan Hospital of Traditional Chinese Medicine from June 2019 to June 2022 and 50 women of the same age who underwent physical examination during the same period (normal control group) were collected retrospectively. The patients in the PCOS group were divided into two subgroups according to the homeostatic model assessment for insulin resistance index (HOMA-IR) evaluated by the steady-state model. Among them, patients with HOMA-IR ≥ 2.69 were divided into the insulin resistance subgroup (PCOS-IR subgroup, 50 cases), and patients with HOMA-IR<2.69 were divided into the non-insulin resistance subgroup (PCOS-NIR subgroup, 38 cases). The level of AMH were measured by electrochemiluminescence, and ovarian interstitial blood flow indicators, including peak blood flow velocity (PSV), pulsation index (PI), and resistance index (RI) were monitored. Pearson correlation test was used to analyze the correlation between serum AMH and insulin resistance and ovarian interstitial blood flow. Meanwhile, Logistic linear regression model was used to analyze the influencing factors of ovarian interstitial blood flow in patients with PCOS.Results:The levels of AMH, HOMA-IR and PSV in the PCOS group were higher than those in the normal control group: (2.13 ± 0.84) μg/L vs. (0.84 ± 0.29) μg/L, 4.6(2.0, 8.4) vs. 1.8(0.5, 3.9), (10.05 ± 1.52) cm/s vs.(6.78 ± 0.89) cm/s; the PI and RI in the PCOS group were lower than those in the control group: (1.14 ± 0.26)% vs. (2.01 ± 0.53)%, (0.37 ± 0.18)% vs. (0.85 ± 0.33)%, there were statistical differences ( P<0.05). The levels of AMH, HOMA-IR and PSV in the PCOS-IR subgroup were higher than those in the PCOS-NIR subgroup: (2.68 ± 0.81) μg/L vs. (1.59 ± 0.43) μg/L, (10.74 ± 2.32) cm/s vs. (7.93 ± 1.90) cm/s, 7.2(3.1, 15.8) vs. 2.1(0.6, 5.3); the PI and RI in the PCOS-IR subgroup were lower than those in the PCOS-NIR subgroup: (0.88 ± 0.35)% vs. (1.52 ± 0.50)%, (0.29 ± 0.04)% vs. (0.51 ± 0.05)%, there were statistical differences ( P<0.05). Pearson correlation analysis showed that the level of AMH were positively correlated with PSV and HOMA-IR ( r = 0.694 and 0.540, P<0.05), but negatively correlated with PI and RI( r = - 0.687 and - 0.692, P<0.05). Logistic linear regression model analysis showed that AMH and HOMA-IR were risk factors for ovarian interstitial blood flow in patients with PCOS( P<0.05). Conclusions:The serum AMH level in patients with PCOS is abnormally high and increases with insulin resistance. At the same time, the imbalance of AMH expression plays an important role in the increase of abnormal ovarian interstitial blood flow.

Effect of community management based on Roy′s adaptation model in patients with chronic obstructive pulmonary disease / 中华健康管理学杂志

Objective:To determine the effect of community management based on the Roy′s adaptation model (RAM) in patients with chronic obstructive pulmonary disease (COPD).Methods:This study was a cluster randomized controlled study, with the community as the cluster unit, and selected 805 COPD patients from 8 communities in Xuzhou City who had completed community registration before June 2019. A total of 735 patients actually completed follow-up and participated in intervention evaluation. They were randomly divided into control group (362 cases) and intervention group (373 cases) by random number table method. The control group received routine follow-up, while the intervention group received RAM intervention for 6 months. The forced expiratory volume in 1 second (FEV1)/forced volume vital capacity (FVC) ratio (FEV 1/FVC) and the modified British medical research council (mMRC) were used to assess the pulmonary function. The hospital anxiety and depression scales (HADS) were used to evaluate the mental health. The Chinese version of the Short Form Coping and Adaption Processing Scale (CAP-15) was used to assess the adaptive capacity. And the St. George′s Respiratory Questionnaire (SGRQ) was used to evaluate the quality of life in COPD patients. The t test or χ 2 test was used for pre-intervention comparisons between groups, and the repetitive measure analysis of variance (ANOVA) was used for post-intervention comparisons between groups. Results:After 6 months intervention, there were no significant differences in FEV 1/FVC radio between the two groups [(0.61±0.11) vs (0.62±0.12)] ( P=0.172). The scores of mMRC [(2.04±0.33) vs (2.77±0.31) points], HAD-A [(5.28±4.28) vs (6.99±4.41) points], HAD-D [(5.82±5.12) vs (7.27±4.93) points] and SGRQ [(40.17±9.30) vs (53.69±9.77) points] were all lower in the intervention group than those in the control group (all P<0.001). The CAPS-15 score was higher in the intervention group than that in the control group [(35.87±3.62) vs (26.1±3.47)] ( P<0.001). Conclusion:RAM could be used in community management of COPD patients, which could improve their dyspnea symptoms and psychological and physiological functions, also improve their adaptability and quality of life.

Expression and clinical significance of maternal embryo leucine zipper kinase in renal clear cell carcinoma / 国际生物医学工程杂志

Objective:To investigate the expression of maternal embryonic leucine zipper kinase (MELK) in renal clear cell carcinoma and its relationship with clinical and pathological characteristics of the patients with renal clear cell carcinoma, and to evaluate its effect on the proliferation of renal clear cell carcinoma.Methods:The expression of MELK in renal clear cell carcinoma and its relationship with the overall survival of patients was analyzed using the gene expression profiling interactive analysis (GEPIA) online database. Cancer tissue samples from 77 patients with renal clear cell carcinoma treated at Xinxiang Central Hospital were collected, all of which have been confirmed as renal clear cell carcinoma through immunohistochemistry experiments. The relationship between the expression of MELK in renal clear cell carcinoma tissue and the clinical and pathological characteristics of the patients was analyzed. The effect of MELK on the proliferation of renal clear cell carcinoma cells was explored through cloning experiments and CCK-8 assay.Results:Information from the GEPIA database revealed that the expression level of the MELK gene was upregulated in renal clear cell carcinoma compared with normal tissues. The clinicopathological analysis results showed that MELK expression was significantly correlated with tumor size and diameter of renal clear cell carcinoma ( P < 0.05), and had no statistically significant correlation with patient age, gender, or tumor differentiation. The results of the clonogenic assay and the CCK-8 assay showed that MELK expression promoted the proliferation of renal clear cell carcinoma cells (all P < 0.05). Conclusions:MELK promotes the proliferation of kidney cancer cells, which may provide a new therapeutic strategy for the treatment of renal clear cell carcinoma.

Cellular and Molecular Mechanisms of Intestinal Fibrosis

Intestinal fibrosis associated stricture is a common complication of inflammatory bowel disease usually requiring endoscopic or surgical intervention. Effective anti-fibrotic agents aiming to control or reverse intestinal fibrosis are still unavailable. Thus, clarifying the mechanism underpinning intestinal fibrosis is imperative. Fibrosis is characterized by an excessive accumulation of extracellular matrix (ECM) proteins at the injured sites. Multiple cellular types are implicated in fibrosis development. Among these cells, mesenchymal cells are major compartments that are activated and then enhance the production of ECM. Additionally, immune cells contribute to the persistent activation of mesenchymal cells and perpetuation of inflammation. Molecules are messengers of crosstalk between these cellular compartments. Although inflammation is necessary for fibrosis development, purely controlling intestinal inflammation cannot halt the development of fibrosis, suggesting that chronic inflammation is not the unique contributor to fibrogenesis. Several inflammation-independent mechanisms including gut microbiota, creeping fat, ECM interaction, and metabolic reprogramming are involved in the pathogenesis of fibrosis. In the past decades, substantial progress has been made in elucidating the cellular and molecular mechanisms of intestinal fibrosis. Here, we summarized new discoveries and advances of cellular components and major molecular mediators that are associated with intestinal fibrosis, aiming to provide a basis for exploring effective anti-fibrotic therapies in this field.

Impact of asthma action plan-based remote joint management model on asthma control in children / 中华儿科杂志

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.

Application and prospect of drug discrimination in field of drug abuse / 中国药理学通报

Drug discrimination is a behavioral pharmacological technique to study the discriminative stimulus effects of drug. Currently drug discrimination has been widely used in preclinical drug development of CNS drugs, the most extensive of which is psychodependent research in the field of drug abuse. This review describes in general the basic principles of drug discrimination, preliminarily elaborates on the relevant characteristics and applications of the subjective effects, time-course effect, stereo specificity, individual differences, and receptor mechanisms, and its development prospects for hallucinogens and cannabis drugs are also presented.

Six new coumarins from the roots of Toddalia asiatica and their anti-inflammatory activities / 中国天然药物

We reported the discovery of six novel coumarins, toddasirins A-F (1-6), each endowed with modified isoprenyl or geranyl side chains, derived from the roots of Toddalia asiatica. Comprehensive structural elucidation was achieved through multispectroscopic analyses, single-crystal X-ray diffraction experiments, and advanced quantum mechanical electronic circular dichroism (ECD) calculations. Furthermore, the anti-inflammatory activity of these compounds was assessed. Notably, compounds 1-3 and 6 demonstrated notable inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW 264.7 cells, with 50% inhibitory concentration (IC50) values of 3.22, 4.78, 8.90, and 4.31 μmol·L-1, respectively.

Comparison of Functional Status Between Diabetic Patients With and Without Nephropathy Based on the International Classification of Functioning,Disability and Health Rehabilitation Set / 中国医学科学院学报

Objective To compare the functional status of diabetic patients with and without nephropathy and identify the items that diabetic patients with nephropathy are more likely to develop dysfunction than diabetic patients without nephropathy based on the international classification of functioning,disability and health rehabilitation set(ICF-RS).Methods A cross-sectional study was conducted.A total of 320 diabetic patients hospitalized in Guangdong Provincial Hospital of Chinese Medicine from August 2021 to February 2022 were selected and assigned into a group with nephropathy and a group without nephropathy.The general characteristics,clinical examination,and laboratory findings were compared by the t test,rank sum test,and Chi-squared test.The functional status of the patients was compared between the two groups by the t test based on the ICF-RS.Logistic regression was employed to control interferential factors between the two groups and identify the association between nephropathy and ICF-RS problematic items among diabetic patients.Results The diabetic patients with nephropathy had more problematic items in ICF-RS(P<0.001),the body function dimension(P=0.003),the activity dimension(P<0.001),and the participation dimension(P<0.001)than those without nephropathy.Moreover,the diabetic patients with nephropathy experienced severer problems in 5 body function items(energy and drive functions,sleep functions,sexual functions,exercise tolerance functions,and muscle power functions),10 activity items(transferring oneself,walking,moving around using equipment,moving around,washing oneself,caring for body parts,toileting,dressing,doing housework,and looking after one's health),and 4 participation items(using transportation,assisting others,basic interpersonal interactions,and recreation and leisure)(all P<0.05).The Logistic regression results showed that compared with the diabetic patients without nephropathy,the diabetic patients with nephropathy were more likely to develop problems in energy and drive functions(aOR=4.35,95%CI=1.28-14.79,P=0.019),emotional functions(aOR=1.88,95%CI=1.06-3.34,P=0.031),sexual functions(aOR=3.39,95%CI=1.82-6.34,P<0.001),moving around(aOR=3.11,95%CI=1.76-5.52,P<0.001),doing housework(aOR=17.48,95%CI=3.57-85.60,P<0.001),looking after one's health(aOR=1.97,95%CI=1.13-3.43,P=0.017),using transportation(aOR=2.59,95%CI=1.38-4.88,P=0.003),and recreation and leisure(aOR=2.52,95%CI=1.46-4.35,P<0.001).Conclusion Compared with the diabetic patients without nephropathy,the patients with nephropathy suffer more ICF-RS problematic items and are more likely to develop dysfunction in certain items in all the three dimensions.

A review of research on psychological and behavioral problems in children with autism spectrum disorder during the coronavirus disease 2019 epidemic / 中国当代儿科杂志

Since December 2019, coronavirus disease 2019 (COVID-19) has been rapidly spreading worldwide and affecting the physical and mental health of the general population. It may have even more serious potential harm to children with autism spectrum disorder (ASD). This paper provides a literature review on the psychological and behavioral problems experienced by children with ASD during the COVID-19 epidemic, as well as the factors influencing these issues. The findings of this review can serve as a basis for clinical research on ASD children.

Association between blood glucose-to-lymphocyte ratio and prognosis of patients with sepsis-associated acute kidney injury / 中华危重病急救医学

OBJECTIVE@#To investigate the association between the glucose-to-lymphocyte ratio (GLR) and prognosis of patients with sepsis-associated acute kidney injury (SA-AKI).@*METHODS@#Based on the Medical Information Mart for Intensive Care-IV (MIMIC-IV), SA-AKI patients aged ≥ 18 years were selected. According to the tertiles of GLR, the patients were divided into GLR1 group (GLR ≤ 4.97×10-9 mmol), GLR2 group (4.97×10-9 mmol < GLR < 9.75×10-9 mmol) and GLR3 group (GLR ≥ 9.75×10-9 mmol). Patients with SA-AKI were divided into survival group and death group according to whether they survived 28 days after admission. The patient's gender, age, vital signs, laboratory test results, comorbidities, sequential organ failure assessment (SOFA), acute physiology score III (APS III) score and treatment measures were extracted from the database. Kaplan-Meier survival analysis was used to make the survival curves of patients with SA-AKI at 28 days, 90 days, 180 days and 1 year. Multivariate Logistic regression analysis model was used to explore the independent risk factors of 28-day mortality in patients with SA-AKI. Receiver operator characteristic curve (ROC curve) was used to analyze the predictive efficacy of GLR for the prognosis of patients with SA-AKI.@*RESULTS@#A total of 1 524 patients with SA-AKI were included, with a median age of 68.28 (58.96, 77.24) years old, including 612 females (40.16%) and 912 males (59.84%). There were 507 patients in the GLR1 group, 509 patients in the GLR2 group and 508 patients in the GLR3 group. There were 1 181 patients in the 28-day survival group and 343 patients in the death group. Grouping according to GLR tertiles showed that with the increase of GLR, the 28-day, 90-day, 180-day and 1-year mortality of SA-AKI patients gradually increased (28-day mortality were 11.64%, 22.00%, 33.86%, respectively; 90-day mortality were 15.98%, 26.72%, 40.55%, respectively; 180-day mortality were 17.16%, 28.29% and 41.73%, and the 1-year mortality were 17.95%, 29.27% and 42.72%, respectively, all P < 0.01). According to 28-day survival status, the GLR of the death group was significantly higher than that of the survival group [×10-9 mmol: 9.81 (5.75, 20.01) vs. 6.44 (3.64, 10.78), P < 0.01]. Multivariate Logistic regression analysis showed that GLR was an independent risk factor for 28-day mortality in patients with SA-AKI [when GLR was used as a continuous variable: odds ratio (OR) = 1.065, 95% confidence interval (95%CI) was 1.045-1.085, P < 0.001; when GLR was used as a categorical variable, compared with GLR1 group: GLR2 group OR = 1.782, 95%CI was 1.200-2.647, P = 0.004; GLR3 group OR = 2.727, 95%CI was 1.857-4.005, P < 0.001]. ROC curve analysis showed that the area under the ROC curve (AUC) of GLR for predicting 28-day mortality in patients with SA-AKI was 0.674, when the optimal cut-off value was 8.769×10-9 mmol, the sensitivity was 57.1% and the specificity was 67.1%. The predictive performance was improved when GLR was combined with APS III score and SOFA score, and the AUC was 0.806, the sensitivity was 74.6% and the specificity was 71.4%.@*CONCLUSIONS@#GLR is an independent risk factor of 28-day mortality in patients with SA-AKI, and high GLR is associated with poor prognosis in patients with SA-AKI.

Decision Self-Efficacy and Decisional Conflict on Reintubation among Surrogates of Ventilated Patients Undergoing Planned Extubation

Purpose@#Although the medical decision-making process can be overwhelming for some surrogates, there is a lack of understanding regarding their experiences. The objectives of this study were to examine the decision self-efficacy and decisional conflict experienced by surrogates in intensive care units (ICUs) when faced with the decision of whether to reintubate patients with respiratory failure after a planned extubation. In addition, predictors and mediators influencing these decision-making processes were identified. @*Methods@#This study utilized a cross-sectional design to investigate the decision-making processes of 174 surrogates who were faced with the decision of whether to reintubate patients with respiratory failure after a planned extubation in the internal ICU of a medical center between August 2021 and February 2022. Structured questionnaires were administered to collect data on the surrogates' background information, decision self-efficacy, decisional conflict, and positive and negative affect. The patients’ background information was also collected. Univariate and multivariate analyses were performed to model the data. @*Results@#The mean decision self-efficacy score of the surrogates was 82.41 points, and 20.7% surrogates had decisional conflict scores exceeding 37.5 points, suggesting that they faced challenges in the decision-making process. Surrogates' employment status and negative affect significantly predicted their decision self-efficacy. In addition, patients' activities of daily living prior to hospitalization and the decision self-efficacy of the surrogate significantly predicted surrogate decisional conflict. The impact of surrogates’ negative affect on decisional conflict was fully mediated by decision self-efficacy. @*Conclusions@#Surrogate decision self-efficacy mediates the relationship between negative affect and decisional conflict. Providing clinical care interventions that focus on enhancing surrogate self-efficacy and reducing negative affect can help alleviate decisional conflict in this population.

Etiology of ascites in 165 children / 中国当代儿科杂志

OBJECTIVES@#To study the etiology and clinical features of children with ascites, so as to provide a basis for the diagnosis and treatment of ascites in children.@*METHODS@#The medical data of the children with ascites, who were hospitalized from January 1, 2010 to December 31, 2019, were retrospectively reviewed.@*RESULTS@#Among the 165 children with ascites, the male/female ratio was 1.53:1, and the mean age of onset was (6±4) years. The causes of ascites included surgical acute abdomen (39 children, 23.6%), infectious diseases (39 children, 23.6%), neoplastic diseases (27 children, 16.4%), hepatogenic diseases (18 children, 10.9%), pancreatitis (10 children, 6.1%), cardiogenic diseases (8 children, 4.8%), rheumatic immune diseases (6 children, 3.6%), and nephrogenic diseases (5 children, 3.0%). According to the age of onset, there were 33 infants, 24 young children, 30 preschool children, 41 school-aged children, and 37 adolescents. Surgical acute abdomen and hepatogenic diseases were the main causes of ascites in infants (P<0.05). Neoplastic disease was the leading cause in young children (P<0.05). Infectious diseases were the most common cause in adolescents (P<0.05).@*CONCLUSIONS@#Surgical acute abdomen, infectious diseases, neoplastic diseases, and hepatogenic diseases are the common causes of ascites in children, and there are some differences in the leading cause of ascites between different age groups.

The effect of extracellular vesicles derived from lung tissue on intrapulmonary inflammation and formation of neutrophil extracellular traps in sepsis rats / 中华急诊医学杂志

Objective:To investigate the effect of extracellular vesicles derived from lung tissue on intrapulmonary inflammation and the formation of neutrophil extracellular traps (NETs) in sepsis rats.Methods:Sepsis rat model was established by cecal ligation and puncture (CLP). Collagenase D and DNase I were used to dissociate the lung tissue, the impurities were removed by centrifugation, and finally, the extracellular vesicles (Ti-EVs) derived from lung tissue were separated and extracted by differential ultracentrifugation. Eighteen male SD rats were randomly divided into the sham group, sepsis group and Ti-EVs group: in the Ti-sEV group, a sepsis model was established by CLP, and Ti-EVs suspension was instilled through the airway; rats in the CLP group received CLP, and an equal volume of PBS was instilled through the airway; and rats in the sham group was treated with sham operation. The pathological changes of lung tissue were detected by hematoxylin-eosin (HE) staining after 24 h. The content of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the bronchoalveolar lavage fluid (BALF) was measured by enzyme-linked immunosorbent assay (ELISA). Immunofluorescence was used to detect the NETs content in lung tissue.Results:The isolated extracellular vesicles derived from rat lung tissue were observed by transmission electron microscopy as double-layer circular cystic vesicles with particle diameter mainly distributed at 150 nm. Western blot showed positive expression of EVs markers CD9, CD63, and Tsg101. HE staining of lung tissue showed alveolar integrity damage and a large number of inflammatory cells infiltrated in the lung of sepsis rats. Compared with the CLP group, the degree of lung tissue damage was more serious in the Ti-EVs group and the levels of IL-1β, TNF-α and IL-6 in the BALF of rats were significantly increased ( P<0.01). The formation of NETs in the lungs of the rats in the sepsis group and the Ti-EVs group was observed under the laser confocal microscope. Compared with the sepsis group, the fluorescence intensity of NETs in the lung tissues of the Ti-EVs group increased significantly. Conclusions:After enzymatic digestion, differential ultracentrifugation and other treatments, the extracellular vesicles derived from rat lung tissue with high purity can be successfully isolated and extracted. In the process of septic lung injury, extracellular vesicles in lung tissue can aggravate the inflammatory response in the lung and promote the formation of NETs.

Analysis of the current status of knowledge, attitude and practice of metabolic syndrome and its influencing factors among the elderly in Beijing community / 中华老年医学杂志

Objective:To understand the status of knowledge, attitude and practice of metabolic syndrome(MS) among the elderly in the community and analyze its influencing factors, so as to provide guidance for the prevention and treatment of MS.Methods:From January 2021 to August 2021, permanent residents(residence duration ≥6 months)aged 65 and above with regular health check examination in Fangzhuang Community Health Service Center of Fengtai District, Beijing were investigated using self-designed MS knowledge, attitude and practice questionnaire.After excluding 34 incomplete questionnaires, the 491 valid questionnaires were recycled with questionnaire valid percentage of 93.5%(491/525). The survey results were analyzed by descriptive analysis, Mann-Whitney U test, Kruskal-Wallis H test and multiple linear regression analysis and multiple linear regression.Results:The scores of MS knowledge, attitude and practice of the elderly in the community were 7(5, 10), 9(8, 10)and 19(18, 21)respectively.The correct answer rate of the diagnostic criteria of MS components was less than 50%.The score of knowledge about MS in the elderly was positively correlated with the scores of attitudes( r=0.263)and practice( r=0.134)(all P<0.01). The results of univariate and multiple linear regression analysis showed that gender, attending educational lectures and the prevalence of MS were the influencing factors of MS knowledge score(all P<0.05). Leisure time, attending educational lectures, pre-retirement occupation and regular health check examination were the influencing factors for MS attitude score(all P<0.05); attending educational lectures, leisure time, regular health check examination and pre-retirement occupation were the influencing factors for MS practice score(all P<0.05). Conclusions:The elderly in the community have a low level of knowledge about the components and diagnostic criteria of MS, but have a positive attitude and practice towards the prevention and treatment of MS.The level of knowledge, attitude and practice of MS is affected by health education lectures, occupation, regular health check examination and other factors.Health education on the diagnostic criteria and the awareness of disease prevention for the elderly in the community should be strengthened to improve the levels of the knowledge, attitude and practice of MS.

Evaluation of China Comprehensive AIDS Response Program in 2020 / 中华流行病学杂志

Objective: To analyze the work indicators of China Comprehensive AIDS Response Program (China CARES) and provide reference for future work of the program. Methods: The scores of each indicator were calculated, and different scores among different types of program areas were compared. The M(Q1,Q3) was used to describe the score of each indicator. The entropy weight method was used to calculate the composite score of each indicator and the composite score was translated into a 100-point system and compared among indicators. Results: In terms of the first-level indicators, organizational leadership and management (96.0 points), publicity and education (94.0 points), and innovative strategies and measures (98.0 points) got relatively high scores; while comprehensive social governance of AIDS prevention (72.0 points) was with the lowest score. The scores of publicity and education and comprehensive intervention in county-level program areas were significantly lower than those in urban areas. For secondary indicators, the indicator with relatively lower scores included "condom use among female sex workers last time" (70.0 points)", "at least one local key population has an increase in the number of people receiving HIV testing compared with the previous year" (70.0 points)", "colleges and occupational schools set up AIDS-related self-service facilities" (65.0 points), "HIV testing among the arrested people suspected of prostitution, adultery, drug users and traffickers" (55.0 points) and "condom use among men who have sex with men during last episode" (50.0 points). The "indicator 3 comprehensive intervention" contributed most to the evaluation, while "indicator 7 innovation strategies and measures" played a minor role in the evaluation results. Conclusions: The overall situation of AIDS Response Program in 2020 was good, but the progress in different word areas was not yet balanced. The two areas of comprehensive intervention and comprehensive social governance of AIDS prevention should be strengthened. It is also suggested that relevant indicators be adjusted appropriately to improve evaluation indicators system and comprehensively promote the program.