ObjectiveTo decipher the mechanism by which Zuoguiwan （ZGW） treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 （DRD4）/nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4） signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone （0.35 mg·kg^-1）. After successful modeling， the rats were randomized into model， methimazole （positive control， 5 mg·kg^-1）， low-， medium-， and high-dose （1.85， 3.70， 7.40 g·kg^-1， respectively） ZGW， and normal control groups. After 21 days of continuous gavage， the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones ［triiodothyronine （T₃）， thyroxine （T₄）， thyroid-stimulating hormone （TSH）］， renal function indexes ［serum creatine （Scr） and blood urea nitrogen （BUN）］， energy metabolism markers ［cyclic adenosine monophosphate （cAMP） and cyclic guanosine monophosphate （cGMP）］， and oxidative stress-related factors ［superoxide dismutase （SOD）， malondialdehyde （MDA）， and NADPH）］ were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was employed to analyze the expression of DRD4， NOX4， mitochondrial respiratory chain complex proteins ［NADH：ubiquinone oxidoreductase subunit S4 （NDUFS4） and cytochrome C oxidase subunit 4 （COX4）］， and inflammation-related protein ［tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， p38 mitogen-activated protein kinase （MAPK）］ pathway in the renal tissue. ResultsCompared with the normal group， the model group showed mental malaise， body weight decreases （P<0.01）， inflammatory cell infiltration in the renal tissue， a few residual parotid glands in the thyroid， elevations in serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA， and NADPH （P<0.01）， down-regulation in protein levels of TSH， SOD， and DRD4 （P<0.05， P<0.01）， and up-regulation in expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.01）. Compared with the model group， ZGW increased the body weight （P<0.05， P<0.01）， reduced the infiltration of renal interstitial inflammatory cells， restored the thyroid structure and follicle size， lowered the serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA and NADPH （P<0.05， P<0.01）， up-regulated the expression of TSH， SOD and DRD4 （P<0.05， P<0.01）， and down-regulated the expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.05， P<0.01）. Moreover， high-dose ZGW outperformed methimazole （P<0.05）. ConclusionBy activating DRD4， ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway， reduce oxidative stress and inflammatory response， thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.

Methods:Cultured human alveolar epithelial A549 cells were assigned into LPS group and blank control group. LPS group was stimulated with LPS and adenosine triphosphate to induce pyroptosis and inflammation. A549 cells were divided into 4 groups: miR-20a mimics group, mimics-negative control (NC) group, inhibitor group and inhibitor-NC group. MiRNA-20a mimics, mimics-NC, inhibitor, and inhibitor-NC were transfected respectively into A549 cells, and after 24 h, the cells were collected to verify transfection efficiency by qPCR. MiRNA-20a mimics and the constructed TLR4-3'UTR double luciferase reporter plasmid were co-transfected into A549 cells, and luciferase activity was analyzed. MiRNA-20a mimics/inhibitors were transfected into A549 cells, and then the cells were stimulated by LPS for 8 h followed by adenosine triphosphate for 30 min. QPCR, Western Blot and ELISA were used to detect the expression of GSDMD, inflammatory factors (ASC, NLRP3, Caspase-1, IL-1β) and Signaling molecules (TLR4、NF-κB) in A549 cells at mRNA level and protein level. Immunofluorescence was used to detect the expression of TLR4 in the A549 cells and NF-κB in the nucleus of A549 cells after transfecting with miRNA-20a mimics/inhibitor.Results:The mRNA and protein expression of pyroptosis marker molecule (GSDMD) and inflammatory factors (ASC, NLRP3, Caspase-1, IL-1β) in A549 cells stimulated with LPS were significantly higher than those in the blank control group, and the differences were statistically significant ( P<0.05). The expression of miRNA-20 in the mimics group was significantly higher than that in the mimic-NC group ( P<0.05), while the expression of miRNA-20a in the inhibitor group was lower than that in the inhibitor-NC group ( P<0.01). The double luciferase reporter gene experiment showed that the relative fluorescence value of the co-transfection group for TLR4-3'UTR-WT and miRNA-20a mimics was significantly lower than the co-transfection group for TLR4-3'UTR-WT and miRNA-20a mimics-NC ( P<0.05). The mRNA and protein levels of pyroptosis marker molecule (GSDMD) , inflammatory factors (ASC, NLRP3, Caspase-1, IL-1β) and signaling molecules (TLR4, NF-κB) were decreased in the mimics group compared to the mimics-NC group, and increased in inhibitor group compared to inhibitor-NC group. Conclusions:miRNA-20a may inhibit LPS-induced pyroptosis and inflammation of A549 cells via TLR4/NF-κB signal pathway.Objetive:To explore the potential role of miRNA-20a in lipopolysaccharide (LPS) induced pyroptosis and inflamation of human alveolar epithelial A549 cells and its regulation mechanisim.

Objective:The present study aims to determine the potential mediating role of intrusive imagery in the correlation between body dissatisfaction and the risk of eating disorders in college students. The effects of cognitive reappraisal and expressive suppression were also investigated.Methods:Using convenient sampling method, a total of 5 746 participants from four cities in China completed on line the Satisfaction and Dissatisfaction with Body Parts Scale, Intrusive Visual Imagery Questionnaire, Eating Disorder Inventory, and Emotion Regulation Questionnaire to investigate the level of body dissatisfaction, the level of intrusive imagery, the risk of eating disorders, and the utilization of emotion regulation strategies in college students. Mediational analysis with multiple regression were conducted to reveal the potential roles of intrusive imagery as a mediation factor and the two emotion regulation strategies as moderators.Results:Body dissatisfaction was positively related to the risk of eating disorders (β=0.19, t=13.03, P<0.01). This correlation remained significant when intrusive imagery was introduced as a mediating factor (β=0.09, t=7.00, P<0.01). Both cognitive reappraisal and expressive suppression could moderate the relationship of body dissatisfaction and intrusive imagery, as well as the relationship of body dissatisfaction and the risk of eating disorders. Simple slope analysis showed that higher tendency of using cognitive reappraisal was associated with enhanced impact of body dissatisfaction on invasive imagery (simple slope=0.28 and 0.24, for high score cognitive-reappraisal individuals and low-score ones, respectively, P<0.01) and on the risk of eating disorders (simple slope=0.29 and 0.23, for high-score and low-score individuals, respectively, P<0.01). Similarly, higher tendency of using expressive suppression was associated with enhanced impact of body dissatisfaction on invasive imagery (simple slope=0.27 and 0.21, for high score expressive-suppression individuals and low-score ones, respectively, P<0.01) and on the risk of eating disorders (simple slope=0.25 and 0.17, for high-score and low-score individuals, respectively, P<0.01). Conclusion:Intrusive imagery plays a mediating role in the relationship of body dissatisfaction and the risk of eating disorders. Meanwhile, both of the two emotional regulation strategies, cognitive reappraisal and expressive suppression, moderate the impact of body dissatisfaction, on intrusive imagery and on the risk of eating disorders.

Objective:The present study aims to determine the potential mediating role of intrusive imagery in the correlation between body dissatisfaction and the risk of eating disorders in college students. The effects of cognitive reappraisal and expressive suppression were also investigated.Methods:Using convenient sampling method, a total of 5 746 participants from four cities in China completed on line the Satisfaction and Dissatisfaction with Body Parts Scale, Intrusive Visual Imagery Questionnaire, Eating Disorder Inventory, and Emotion Regulation Questionnaire to investigate the level of body dissatisfaction, the level of intrusive imagery, the risk of eating disorders, and the utilization of emotion regulation strategies in college students. Mediational analysis with multiple regression were conducted to reveal the potential roles of intrusive imagery as a mediation factor and the two emotion regulation strategies as moderators.Results:Body dissatisfaction was positively related to the risk of eating disorders (β=0.19, t=13.03, P<0.01). This correlation remained significant when intrusive imagery was introduced as a mediating factor (β=0.09, t=7.00, P<0.01). Both cognitive reappraisal and expressive suppression could moderate the relationship of body dissatisfaction and intrusive imagery, as well as the relationship of body dissatisfaction and the risk of eating disorders. Simple slope analysis showed that higher tendency of using cognitive reappraisal was associated with enhanced impact of body dissatisfaction on invasive imagery (simple slope=0.28 and 0.24, for high score cognitive-reappraisal individuals and low-score ones, respectively, P<0.01) and on the risk of eating disorders (simple slope=0.29 and 0.23, for high-score and low-score individuals, respectively, P<0.01). Similarly, higher tendency of using expressive suppression was associated with enhanced impact of body dissatisfaction on invasive imagery (simple slope=0.27 and 0.21, for high score expressive-suppression individuals and low-score ones, respectively, P<0.01) and on the risk of eating disorders (simple slope=0.25 and 0.17, for high-score and low-score individuals, respectively, P<0.01). Conclusion:Intrusive imagery plays a mediating role in the relationship of body dissatisfaction and the risk of eating disorders. Meanwhile, both of the two emotional regulation strategies, cognitive reappraisal and expressive suppression, moderate the impact of body dissatisfaction, on intrusive imagery and on the risk of eating disorders.