Objective To evaluate the effect of recombinant human tumor necrosis factor receptor type Ⅱ:IgG Fc fusion protein (rhTNFR:Fc,trade name Etanercept) combined with methotrexate on levels of interleukin-17A (IL-17A) and tumor necrosis factor-α (TNF-α) in the serum and mononuclear cells of patients with moderate to severe plaque psoriasis.Methods A total of 30 patients with moderate to severe plaque psoriasis were enrolled from Department of Dermatology of Tenth People's Hospital of Tongji University between August 2014 and February 2016,and then were randomly and equally divided into Etanercept group and Etanercept + methotrexate group.The treatment lasted 24 weeks.Fifteen healthy blood donors served as healthy control group.Enzyme-linked immunosorbent assay (ELISA) and real-time quantitative PCR were performed to measure the serum levels and mRNA expression of IL-17A and TNF-α,respectively,in the patients of the above two groups before and after the treatment.Results Before the treatment,the serum levels of IL-17A and TNF-ct,as well as the mRNA expression of IL-17A and TNF-α in peripheral blood mononuclear cells (PBMCs),were all significantly higher in all the patients than in the healthy controls (all P ＜ 0.05).After the treatment,compared with the Etanercept group,the Etanercept + methotrexate group showed significantly lower serum levels of IL-17A (142.67 ± 14.82 vs.163.54 ± 23.18,P ＜ 0.05) and TNF-α (70.07 ± 25.02 vs.91.98 ± 14.62,P ＜ 0.05),as well as lower mRNA expression of IL-17A (1.12 ± 0.33 vs.1.56 ± 0.77,P ＜ 0.05) and TNF-α in PBMCs (2.50 ± 1.04 vs.3.61 ± 2.14,P ＜ 0.05).Conclusion Etanercept combined with methotrexate is superior to Etanercept alone in the treatment of psoriasis,and can reduce treatment duration and improve therapeutic effect,likely by down-regulating the expression of IL-17A and TNF-α.

ObjectiveTo investigate the impacts of circadian misalignment on glucose uptake of skeletal muscle and metabolism in rats. MethodsA total of 36 male Wistar rats were divided into circadian alignment (CA, normal light-dark cycles, n = 18) and circadian misalignment (CM, shifted light-dark cycles, n = 18) groups. ClockLab behavior analysis was performed for 18 days (61 to 78 days after modeling). Intraperitoneal injection glucose tolerance test and physiologic measures were performed 85 days after modeling. They were euthanized 91 to 92 days after modeling, at 8:00, 12:00, 16:00, 20:00, 24:00 and 4:00 next day. Gastrocnemius tissue was collected and measured for Bmal1, Clock, Per2, Tbc1d1, Glut4 and Pgc1α by reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR). ResultsThe circadian cycle increased (t = -6.557, P < 0.001), the amplitude decreased (t = 2.326, P = 0.030) and the area under curve (AUC) of the blood glucose of intraperitoneal glucose tolerance test decreased (t = -2.622, P = 0.016) in CM group. In gastrocnemius, there was difference in the expression of the Bmal1 (F = 6.691, P < 0.001), Clock (F = 4.188, P = 0.007), Per2 (F = 10.893, P < 0.001), Tbc1d1 (F = 3.411, P = 0.018), Glut4 (F = 5.439, P = 0.002) and Pgc1α (F = 15.376, P < 0.001) across different time; meanwhile, there was difference in the expression of Bmal1 (F = 5.020, P = 0.035), Per2 (F = 8.996, P = 0.006), Tbc1d1 (F = 51.111, P < 0.001) and Pgc1α (F = 10.177, P = 0.004) between groups, and the total Tbc1d1 expression decreased in CM group (t = 4.349, P < 0.001). ConclusionCM induced by shifted light-dark cycles may lead to glucose tolerance impairment in rats, which may be related to the decreased expression of Tbc1d1 and the changes of transcription rhythm of Bmal1, Per2 and Pgc1α in gastrocnemius.

ObjectiveTo explore sleep disturbance in preschool children with autism spectrum disorder (ASD) and analyze the relationship between sleep disturbance and social behavior. MethodsFrom December, 2020 to December, 2022, 221 preschool children with ASD from Beijing Bo'ai Hospital and other two institutes, and 246 healthy preschool children socially recruited were investigated with Children's Sleep Habits Questionnaire (CSHQ). A total of 47 ASD children and 47 healthy children were selected from them to wear a sleep monitoring watch for seven days, while the ASD children were evaluated with Gesell Development Diagnosis Scale (GDDS), Psychoeducational Profile-Third Edition (PEP-3), Autism Diagnostic Observation Schedule-2 (ADOS), Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS) and Social Responsiveness Scale (SRS). ResultsAll the factor-scores were more in the ASD children than in the healthy children (t > 2.491, P < 0.05), except that of daytime sleepiness. The prevalence of sleep disturbance (CSHQ ≥ 41) was 89.6% in ASD children, which was more than that of the healthy children (76.8%) (χ² = 13.360, P < 0.001). The sleep problems in ASD children included bedtime resistance, sleep anxiety, sleep duration, sleep onset delay, parasomnias and sleep disordered breathing. ASD children were shorter in total bedtime, shorter in total sleep time, longer in sleep latency, longer in awake time and lower in sleep efficiency (|t| > 2.001, P < 0.05), compared with those of healthy children. For ASD children, the total bedtime negatively correlated with GDDS-language, PEP-3-expressive language, PEP-3-communication and PEP-3-maladaptive behaviors (r < -0.300, P < 0.05); the sleep efficiency negatively correlated with total score of CARS (r = -0.365, P < 0.05); sleep latency correlated with GDDS-social, PEP-3-cognitive, PEP-3-expressive language, PEP-3-receptive language, PEP-3-visual-motor imitation, PEP-3-characteristic verbal behaviors, PEP-3-communication, original score of ADOS, ADOS-social affect, and total score of CARS (|r| > 2.90, P < 0.05); and total awake time positively correlated with total score of CARS (r = 0.406, P < 0.05). ConclusionSleep disturbance is prevalent and various in preschool ASD children, and influence their social behaviors.