Objectives To investigate whether osteoarthritis (OA) progression can be delayed by casticin in rodent models of anterior cruciate ligament transection (ACLT).Methods Eighteen 2-month-old male C57BL/6J mice were randomised into 3 even groups (n =6) subjected respectively to sham-operation,ACLT-vehicle-treatment and ACLT-casticin-treatment.The knee capsule was dissected in the sham-operation group and ACLT on the right knee was conducted in the ACLT-vehicle-treatment and ACLT-casticin-treatment groups.Intragastric administration of the same amount of Tween-80 solution was conducted for the sham-operation and ACLT-vehicle-treatment groups;Intragastric administration of casticin of 20mg/kg was conducted once per day for the ACLT-casticin-treatment group.Bone micro CT (μCT) was quantitated to detect alterations in microarchitecture of femoral condyle subchondral bone.Tartrate resistant acid phosphatase(TRAP) stain and NOX4 immunostaining were conducted to detect relative proteins and the osteoclast changes on the subchondral bone.Articular cartilage degeneration was graded using HE and safranin O-green staining and the Mankin score criteria.Results Compared with the the sham-operation group,the subchondral bone density,trabecular bone volume fraction and trabecular thickness were decreased,and the trabecular space,positive rates of TRAP stain and NOX4 immunostaining and Mankin scores were increased in the ACLT-vehicle-treatment group.All the above comparisons were statistically significant (P ＜ 0.05).Compared with ACLT-vehicle-treatment group,the subchondral bone density and trabecular bone volume fraction were increased,and the trabecular space,positive rates of TRAP stain and NOX4 immunostaining and Mankin scores were decreased in the ACLT-casticin-treatment group.All the above comparisons were statistically significant (P ＜0.05).Conclusion As casticin may attenuate early OA progression by inhibiting NOX4 activity in subchondral bone and formation of osteoclasts,it may be a new clue to preventive therapy for OA.

Objective The objective of this study was to utilize proton magnetic resonance spectroscopy (1H-MRS) to assess metabolites in cerebellar nuclei in unmedicated patients with insomnia disorder. Methods 1H-MRS was performed on cerebellar nuclei in 23 unmedicated patients with insomnia disorder (insomnia group) and 18 normal sleepers (control group). N-acetylaspartate (NAA), choline-containing compound (Cho) and creatine (Cr) were measured and the ratios of NAA/Cr and Cho/Cr were determined.Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI) were used to assess the subjective sleep quality and insomnia severity of all subjects, while State-Trait Anxiety Inventory (STAI) and Beck Depression Inventory (BDI) were used to assess the levels of anxiety and depression of all subjects. Sleep parameters of all subjects were measured by polysomnography (PSG). Results Mean NAA/Cr ratio of right cerebellar nuclei in insomnia group was significantly lower than that in control group (1.72±0.37 vs. 2.03±0.50, t=2.280, P=0.028). Mean NAA/Cr ratio of right cerebellar nuclei was significantly higher than that of left cerebellar nuclei within control group (2.03±0.50 vs. 1.68±0.21, t=3.386, P=0.004). There was no significant difference with regard to NAA/Cr ratio between bilateral cerebellar nuclei within insomnia group (t=1.416, P=0.171). Across all subjects, PSQI global scores (r=-0.369, P=0.018), and sleep latency (r=-0.437, P=0.004) and number of awakenings after sleep onset (r=-0.432, P=0.005) measured by PSG were negatively correlated with NAA/Cr ratios of right cerebellar nuclei, while percentages of stage 3 sleep (r=0.377,P=0.015) measured by PSG were positively correlated with NAA/Cr ratios of right cerebellar nuclei,respectively. Conclusion Patients with insomnia disorder have a hemispherically lateralized metabolic disturbance of NAA/Cr in right cerebellar nuclei,indicating that patients with insomnia disorder have neuronal damage in right cerebellar nuclei.

Objective: This study’s objective is to assess the efficacy and safety of Pulsed Magnetic Therapy System (PMTS) in improving insomnia disorder. Methods: Participants with insomnia disorder were randomly assigned to receive either PMTS or sham treatment for four weeks (n= 153; PMTS: 76, sham: 77). Primary outcomes are the Insomnia Severity Index (ISI) scores at week 0 (baseline), 1, 2, 3, 4 (treatment), and 5 (follow-up). Secondary outcomes are the Pittsburgh Sleep Quality Index at baseline and week 4, and weekly sleep diary-derived values for sleep latency, sleep efficiency, real sleep time, waking after sleep onset, and sleep duration. Results: The ISI scores of the PMTS group and the sham group were 7.13±0.50, 11.07±0.51 at week 4, respectively. There was a significant group×time interaction for ISI (F3.214, 485.271=24.25, p<0.001, ηp 2=0.138). Only the PMTS group experienced continuous improvement throughout the study; in contrast, the sham group only experienced a modest improvement after the first week of therapy. At the end of the treatment and one week after it, the response of the PMTS group were 69.7% (95% confidence interval [CI]: 58.6%–79.0%), 75.0% (95% CI: 64.1%–83.4%), respectively, which were higher than the response of the sham group (p<0.001). For each of the secondary outcomes, similar group×time interactions were discovered. The effects of the treatment persisted for at least a week. Conclusion PMTS is safe and effective in improving insomnia disorders.