Myofibrillogenesis regulator-1 (MR-1) is a novel protein involved in cellular proliferation, migration, inflammatory reaction and signal transduction. However, little information is available on the relationship between MR-1 expression and the progression of atherosclerosis. Here we report atheroprotective effects of silencing MR-1 in a model of Ang II-accelerated atherosclerosis, characterized by suppression focal adhesion kinase (FAK) and nuclear factor kappaB (NF-κB) signaling pathway, and atherosclerotic lesion macrophage content. In this model, administration of the siRNA-MR-1 substantially attenuated Ang II-accelerated atherosclerosis with stabilization of atherosclerotic plaques and inhibited FAK, Akt, mammalian target of rapamycin (mTOR) and NF-kB activation, which was associated with suppression of inflammatory factor and atherogenic gene expression in the artery. In vitro studies demonstrated similar changes in Ang II-treated vascular smooth muscle cells (VSMCs) and macrophages: siRNA-MR-1 inhibited the expression levels of proinflammatory factor. These studies uncover crucial proinflammatory mechanisms of Ang II and highlight actions of silencing MR-1 to inhibit Ang II signaling, which is atheroprotective.
Angiotensin II* ; Angiotensins* ; Animals ; Arteries ; Atherosclerosis* ; Cell Proliferation ; Focal Adhesion Protein-Tyrosine Kinases ; Gene Expression ; In Vitro Techniques ; Macrophages ; Mice* ; Muscle Development ; Muscle, Smooth, Vascular ; NF-kappa B ; Plaque, Atherosclerotic ; RNA, Small Interfering ; Signal Transduction ; Sirolimus

Objective:To detect the expression of interleukin 2 (IL-2)/Janus kinase 3/signal transduction and transcriptional activator 5 (JAK3/STAT5) signaling pathway in peripheral blood of patients with ankylosing spondylitis (AS) and explore its mechanism in the development and progression of AS.Methods:Clinical data, peripheral blood and laboratory tests of 30 patients with active AS (ASA), 30 patients with stable AS (ASS) and 50 healthy subjects (HC) were collected. The mRNA expression levels of JAK3, signal transduction and transcription activator 5a (STAT5a) and signal transduction and transcription activator 5b (STAT5b) were detected by quantitative real-time-polymerase chain reaction (RT-qPCR). The expression levels of JAK3, STAT5a and STAT5b proteins and phosphorylated proteins were detected by Western-blot. Plasma IL-2 concentration was determined by enzyme-linked immunosorbent assay (ELISA). Two independent samples t-test or one-way analysis of variance were used for measurement data consistent with normal distribution, LSD- t test was used for pairwise comparison between the three groups, Mann-Whitney U test or Kruskal-Wallis H test was used for non-normal distribution, χ2 test was used for correlation analysis of categorical variables. Spearman correlation analysis was used for correlation analysis between variables, and receiver operating characteristic (ROC) curve was used to evaluate the value of JAK3, STAT5a and STAT5b mRNA expression levels in monitoring AS activity. Results:① The mRNA expression levels of JAK3, STAT5a and STAT5b were significantly different among the three groups ( F=65.98, P<0.001; F=21.15, P<0.001; F=13.67, P<0.001). JAK3 mRNA expression in ASA group (2.5±0.9) was significantly higher than that in ASS group (1.1±0.4) and healthy subjects (1.0±0.5), the difference was statistically significant (both P<0.001). The mRNA expression level of STAT5a in ASA group (1.4±0.3) was significantly higher than that in ASS group (0.9±0.3) and healthy subjects group (1.0±0.3), the difference was statistically significant (both P<0.001). STAT5b mRNA expression level in ASA group (1.5±0.6) was significantly higher than that in ASS group (1.0±0.4) and healthy subjects (1.0±0.4), the difference was statistically significant (both P<0.001). The expression level of JAK3 mRNA in HLA-B27 positive group (1.9±1.0) was higher than that in HLA-B27 negative group (1.4±0.6), and the difference was statistically significant ( t=-2.22, P=0.032). The phosphorylation levels of JAK3, STAT5a and STAT5b showed statistically significant differences among the three groups ( F=91.56, P<0.001; F=25.15, P< 0.001; F=178.59, P<0.001). The phosphorylation level of JAK3 protein in ASA group (1.04±0.08) was significantly higher than that in ASS group (0.568±0.019) and healthy subjects (0.536±0.064), the difference was statistically significant (both P<0.001). The phosphorylation level of STAT5a protein in ASA group (1.166±0.096) was significantly higher than that in ASS group (0.923±0.018) and healthy subjects (0.911±0.017), the difference was statistically significant (both P<0.001). The phosphorylation level of STAT5b protein in ASA group (0.81±0.05) was significantly higher than that in ASS group (0.21±0.03) and healthy subjects (0.24± 0.07), the difference was statistically significant (both P<0.001). The difference of plasma IL-2 concentration among the three groups was statistically significant ( F=3.32, P=0.040). The IL-2 concentration in the ASA group [(110±40) pg/ml] was significantly higher than that in the ASS group [(89±40) pg/ml] and the healthy group [(88±39) pg/ml], the difference was statistically significant ( P=0.044, P=0.016). ② Spearman correlation analysis showed that STAT5a mRNA expression level was positively correlated with platelets in AS patients ( r=0.353, P=0.006). JAK3 mRNA expression level in ASA group was positively correlated with IL-2 concentration ( r=0.766, P<0.001), and negatively correlated with estimated glomerular filtration rate ( r=-0.485, P=0.007). STAT5a mRNA expression level was positively correlated with erythrocyte sedimentation rate ( r= 0.680, P<0.001), and STAT5b mRNA expression level was positively correlated with hypersensitive C-reactive protein (CRP) ( r=0.823, P<0.001). ③ The ROC curve showed that JAK3 mRNA expression level predicted the area under ROC curve (AUC) of ASA with a 95% CI of 0.920 (0.853, 0.987), sensitivity and specificity of 86.7% and 90.0%, respectively. STAT5a mRNA expression level predicted the AUC 95% CI of ASA was 0.874 (0.787, 0.961), and the sensitivity and specificity were 96.7% and 66.7%, respectively. STAT5b mRNA expression level predicted the AUC 95% CI of ASA was 0.749 (0.617, 0.881), and the sensitivity and specificity were 73.3% and 80.0%, respectively. Conclusion:This study suggests that IL-2/JAK3/STAT5 may be involved in the pathogenesis of AS, and JAK3 mRNA can be used as a biological indicator to monitor the activity of AS disease.

Objective:To investigate the psychological crisis status of parents of pediatric bipolar disorder (PBD) patients and establish a risk prediction model, in order to provide a reference for medical workers to screen parents' mental health status early.Methods:This study was a cross-sectional study. Using the convenient sampling method, a total of 478 parents of children with PBD who were treated in the Second Affiliated Hospital of Wenzhou Medical University in Zhejiang Province from January 2020 to May 2021 were selected as the research subjects. They were randomly divided into the modeling group ( n=318) and the validation group ( n=160) in a ratio of 2∶1. Questionnaires were conducted using general information questionnaires and Symptom Self-rating Scale. Univariate analysis and logistic regression were used to analyze the influencing factors of psychological crisis in the modeling group, and H- L test and receiver operating characteristic curve were used to verify the predictive performance of the model. Results:The detection rate of psychological crisis among the parents of 318 children with PBD was 25.7%, of which the detection rate was 26.1% in the modeling group and 25.0% in the validation group. First onset ( OR=2.337, P<0.05) , parental gender ( OR=1.846, P<0.05) , conscious care burden ( OR=3.527, P<0.05) , religious belief ( OR=3.113, P<0.05) and children's age ( OR=1.969, P<0.05) were independent predictors of psychological crisis in parents of children with PBD. Conclusions:Medical workers need to be good at observing the psychological status of parents of children, predict the risk of psychological crisis in parents in advance and timely conduct targeted interventions according to the risk level, so as to improve the psychological adaptability of parents and improve their mental health.

Objective:To investigate the psychological crisis status of parents of pediatric bipolar disorder (PBD) patients and establish a risk prediction model, in order to provide a reference for medical workers to screen parents' mental health status early.Methods:This study was a cross-sectional study. Using the convenient sampling method, a total of 478 parents of children with PBD who were treated in the Second Affiliated Hospital of Wenzhou Medical University in Zhejiang Province from January 2020 to May 2021 were selected as the research subjects. They were randomly divided into the modeling group ( n=318) and the validation group ( n=160) in a ratio of 2∶1. Questionnaires were conducted using general information questionnaires and Symptom Self-rating Scale. Univariate analysis and logistic regression were used to analyze the influencing factors of psychological crisis in the modeling group, and H- L test and receiver operating characteristic curve were used to verify the predictive performance of the model. Results:The detection rate of psychological crisis among the parents of 318 children with PBD was 25.7%, of which the detection rate was 26.1% in the modeling group and 25.0% in the validation group. First onset ( OR=2.337, P<0.05) , parental gender ( OR=1.846, P<0.05) , conscious care burden ( OR=3.527, P<0.05) , religious belief ( OR=3.113, P<0.05) and children's age ( OR=1.969, P<0.05) were independent predictors of psychological crisis in parents of children with PBD. Conclusions:Medical workers need to be good at observing the psychological status of parents of children, predict the risk of psychological crisis in parents in advance and timely conduct targeted interventions according to the risk level, so as to improve the psychological adaptability of parents and improve their mental health.