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Osteoporosis (OP) is a systemic skeletal disease that primarily affects the elderly population, which greatly increases the risk of fractures. Here we report that Kindlin-2 expression in adipose tissue increases during aging and high-fat diet fed and is accompanied by decreased bone mass. Kindlin-2 specific deletion (K2KO) controlled by Adipoq-Cre mice or adipose tissue-targeting AAV (AAV-Rec2-CasRx-sgK2) significantly increases bone mass. Mechanistically, Kindlin-2 promotes peroxisome proliferator-activated receptor gamma (PPARγ) activation and downstream fatty acid binding protein 4 (FABP4) expression through stabilizing fatty acid synthase (FAS), and increased FABP4 inhibits insulin expression and decreases bone mass. Kindlin-2 inhibition results in accelerated FAS degradation, decreased PPARγ activation and FABP4 expression, and therefore increased insulin expression and bone mass. Interestingly, we find that FABP4 is increased while insulin is decreased in serum of OP patients. Increased FABP4 expression through PPARγ activation by rosiglitazone reverses the high bone mass phenotype of K2KO mice. Inhibition of FAS by C75 phenocopies the high bone mass phenotype of K2KO mice. Collectively, our study establishes a novel Kindlin-2/FAS/PPARγ/FABP4/insulin axis in adipose tissue modulating bone mass and strongly indicates that FAS and Kindlin-2 are new potential targets and C75 or AAV-Rec2-CasRx-sgK2 treatment are potential strategies for OP treatment.
RESUMO
Objective:To explore the chain mediating effect of escape motivation and flow experience between frustration and online game addiction.Methods:Stratified cluster sampling method was used to randomly select 740 students from 5 universities in Beijing.Frustrate mental state scale (FMSS), escape subscale of online game motivation scale (OGMS), game flow scale (GFS), and the game addiction subscale of different types of internet addiction scale (DTIAS) were used for investigation. SPSS 25.0 software and PROCESS macro program model 6 were used to analyze the data and test the mediation effect.Results:Frustration (62.94±15.84) was positively correlated with escape motivation(6.89±2.34), flow experience(20.36±7.38), and online game addiction(16.05±6.62) ( r=0.30, 0.19, 0.39, all P<0.01). Escape motivation was positively correlated with flow experience and online game addiction ( r=0.51, 0.50, both P<0.01), while flow experience was positively correlated with online game addiction ( r=0.51, all P<0.01). The direct effect of frustration on game addiction was 0.23 (95% CI=0.17-0.30). Frustration indirectly affects game addiction through two paths. The single mediating effect of escape motivation was 0.07 (95% CI=0.05-0.11), and the chain mediating effect of escape motivation and flow experience was 0.05 (95% CI=0.04-0.08). Conclusion:Frustration not only directly affects online game addiction, but also indirectly affects online game addiction through escape motivation and flow experience.
RESUMO
Objective To explore the patients satisfaction with participation in medical and nursing decision making and the influencing factors among cancer patients, and to provide a basis for developing better medical care services. Methods Totally 159 cancer patients were recruited from Beijing Cancer Hospital, and then were investigated with the general information questionnaire, the patients′ expectation for participation in clinical decision making scale, the patients′ competence for participation in clinical decision making scale, and the patients′satisfaction with participation in medical and nursing decision making questionnaires. Results The total score of patients′satisfaction with participation in medical and nursing decision making were (45.92±3.91) and (34.25±3.31) respectively. Compared with female patients, male patients had higher satisfaction with medical decision making (46.45±3.24&44.87±4.84) and nursing decision making (34.68 ± 2.93&33.42 ± 3.84) (t=2.416, P=0.017;t=2.275, P=0.024);and compared with melanoma patients, lung cancer patients had higher satisfaction with medical decision making (46.51 ± 2.69&43.33 ± 7.07, P=0.002);compared withⅢstage patients, Ⅳstage patients had higher satisfaction with nursing decision making(34.97±2.24&32.40±4.56, P<0.01). Meanwhile, the satisfaction with participation in decision making was significantly positively associated with patients′ expectation and competence for participation in clinical decision making. Conclusions Patients′satisfaction for decision making may vary from different gender, tumor types, disease stages, and patients′expectation and competence. Health care providers still further strength patients′ knowledge and initiative of decision making, and then improve patients′satisfaction with participation in decision making.