Crosstalk between the JAK2 and TGF-β1 signaling pathways in scleroderma-related interstitial lung disease targeted by baricitinib

Abstract Background and objective Systemic sclerosis (SSc) is an immune-mediated rheumatic disease characterized by fibrosis and vascular lesions. Interstitial lung disease is an early complication of SSc and the main cause of death from SSc. Although baricitinib shows good efficacy in a variety of connective tissue diseases, its role in systemic sclerosis-related interstitial lung disease (SSc-ILD) is unclear. The objective of our study was to explore the effect and mechanism of baricitinib in SSc-ILD. Methods We explored crosstalk between the JAK2 and TGF-β1 pathways. In vivo experiments, SSc-ILD mice model were constructed by subcutaneous injection of PBS or bleomycin (7.5 mg/kg) and intragastric administration of 0.5% CMC-Na or baricitinib (5 mg/kg) once every two days. We used ELISA, qRT-PCR, western blot and immunofluorescence staining to evaluate the degree of fibrosis. In vitro experiments, we used TGF-β1 and baricitinib to stimulate human fetal lung fibroblasts (HFLs) and assessed protein expression by western blot. Results The vivo experiments showed that baricitinib notably alleviated skin and lung fibrosis, decreased the concentration of pro-inflammatory factors and increased those of the anti-inflammatory factors. Baricitinib affected the expression of TGF-β1 and TβRI/II inhibitiing JAK2. In the vitro experiments, following the culture of HFLs with baricitinib or a STAT3 inhibitor for 48 h, the expression levels of TβRI/II decreased. Conversely, with successful inhibition of TGF-β receptors in HFLs, JAK2 protein expression decreased. Conclusions Baricitinib attenuated bleomycin-induced skin and lung fibrosis in SSc-ILD mice model by targeting JAK2 and regulating of the crosstalk between the JAK2 and TGF-β1 signaling pathways.

Relationship between oxytocin receptor (OXTR) gene polymorphism and obsessive compulsive disorder in Chinese Han

ABSTRACT Recent research has shown that genetic variations in the oxytocin receptor (OXTR) may be related to variations in subtypes of obsessive-compulsive disorder (OCD). We aimed to explore the relationship between different subtypes of OCD and the genetic variation between rs1316193 and rs4686301 of the OXTR. In this case-control study, 92 OCD patients and 92 healthy controls were included in the OCD and control groups, respectively. The Y-BOCS scale was used to assess the severity of the OCD symptoms. The fasting peripheral blood samples were collected to extract DNA. rs4686301 and rs13316193 were genotyped using restriction fragment length polymorphism analysis techniques. Whether the gene frequency of the locus and the distribution of allele frequency were related to OCD were further study by TaqMan allele typing. The rs4686301 locus differed significantly between behavior and control groups. The genotype frequency and allele frequency at the rs4686301 locus were statistically significant between behavior and control groups (P<0.05). There was significant difference in the genotype frequency at the rs13316193 locus between behavior and control groups (P<0.05). The rs4686301 polymorphism of the OXTR may affect the clinical subtype of OCD. The rs13316193 polymorphism of the OXTR may be a risk factor for obsessive-compulsive behavior.

Characteristics and relationship between self-efficacy and physical activity of college students during COVID-19 epidemic / 中国学校卫生

Objective@#To explore the characteristics and relationship between physical activity and self-efficacy of college students during the COVID-19 epidemic, so as to provide evidence for the orderly development of physical education and curriculum reform of college students after their return to school.@*Methods@#A total of 6 227 college students were collected from 8 districts of China by using convenient sampling method and snowball sampling method, and the physical activity and self-efficacy of all participants were assessed used by the International Physical Activity Questionnaire Short Form (IPAQ-S) and the General Self-Efficacy Scale(GSES).@*Results@#In the terms of general self-efficacy, the score of male students was significantly higher than that of female students, the score of freshman was significantly higher than that of other grades(t/F=7.32, 5.56, P<0.01). In terms of physical activity, the middle and high level physical activity of girls was significantly higher than that of boys, but the proportion of boys meeting the recommended amount was higher(P<0.01). Low level physical activity was the highest in junior college students(31.75%), medium level physical activity was the highest in freshmen (46.75%) and sophomore student (48.13%), and high level physical activity was the highest senior college students (30.40%). The moderate level of physical activity was the highest in all BMI groups, while the lean group had the lowest level of low level physical activity (15.70%) and the highest level of high level physical activity(37.31%), and the lowest proportion meeting the recommended amount(P<0.05). Self-efficacy had a positive predictive effect on physical activity(OR=1.04, 95%CI=1.03-1.05).@*Conclusion@#During the COVID-19 epidemic, there are significant differences in general self-efficacy and physical activity among college students by gender, grade and BMI. The general self-efficacy has a positive impact on physical activity, suggesting that college physical education should pay attention to students- self-efficacy, while considering individual and group differences, and promote physical activity level through self-efficacy improvement.

Transcatheter aortic valve implantation versus surgical aortic valve replacement for treatment of severe aortic stenosis: comparison of results from randomized controlled trials and real-world data

Abstract Objective: Results from randomized controlled trials (RCTs) and real-world study (RWS) appear to be discordant. We aimed to investigate whether data derived from RCTs and RWS evaluating long-term all-cause mortality of transcatheter aortic valve implantation (TAVI) versus surgical aortic valve replacement (SAVR) in patients with severe aortic stenosis (AS) were in agreement. Methods: RCTs or RWS comparing TAVI and SAVR, reporting longterm (≥2-year follow-up) all-cause mortality, were identified. We also carried out subgroup analyses to access the effect in different subgroups. A pre-designated data extraction form including 5 domains and 26 items was used to explore the relationship between RCTs and RWS. Mortality and effect in different subgroups were evaluated using random-effects meta-analyses. Results: Five RCTs (5421 participants, TAVI: 2759, SAVR: 2662) and 33 RWS (20839 participants; TAVI: 6585, SAVR: 14254) were identified. Pooled RCT analysis showed no difference in all-cause mortality between TAVI and SAVR (HR=0.97, 95% CI: 0.88-1.07; P=0.55). In RWS, TAVI was associated with an increased risk of allcause mortality (HR=1.46, 95% CI: 1.26-1.69; P<0.001) compared to SAVR. Conclusion: These results highlight the inconsistencies between RCTs and RWS in assessing long-term all-cause mortality in the treatment of AS using TAVI or SAVR, which may be caused by interactions of clinical characteristics or study design. RCTs as well as RWS are both developing and improving; the advantages of one kind of design, measurement and evaluation can and should be thoughtfully referred to the other.

Cognitive behavioral therapy in combination with systemic family therapy improves mild to moderate postpartum depression

Objective: To explore the effect of cognitive behavioral therapy (CBT) in combination with systemic family therapy (SFT) on mild to moderate postpartum depression and sleep quality. Methods: 249 primiparous women with mild to moderate postpartum depression were recruited and randomly assigned to a control group (n=128), which received conventional postpartum care, or to a psychological intervention group (n=121), which received conventional postpartum care combined with psychological intervention. The Edinburgh Postnatal Depression Scale (EPDS) and Pittsburgh Sleep Quality Index (PSQI) were employed to evaluate depression and sleep quality, respectively. Results: 104 patients in the intervention group and 109 in the control group completed the study. After intervention, the EPDS score, PSQI score, sleep quality score, sleep latency score, sleep duration score, habitual sleep efficiency score, sleep disturbance score, and daytime dysfunction score were significantly lower in the intervention group than in the control group. The EPDS and PSQI scores of each group at different time points after intervention were markedly decreased compared with those before intervention, and the reduction in the intervention group was more evident than that in the control group. Conclusion: CBT in combination with SFT can improve depression and sleep quality in patients with mild to moderate postpartum depression. .