Background To date,pharmacologic therapy is considered the standard first-line treatment for insomnia disorder,but there are still some concerns over the adverse reactions.Repetitive transcranial magnetic stimulation(rTMS)and cognitive behavioral therapy for insomnia(CBT-I)as an alternative to pharmacologic therapy have the advantages of fewer side effects and better patient tolerance in the treatment of chronic insomnia disorder.Objective To explore the clinical efficacy of rTMS and CBT-I on chronic insomnia disorder,so as to provide a novel therapeutic option for the treatment of chronic insomnia disorder.Methods A total of 50 patients with chronic insomnia disorder attending the outpatient clinic of Inner Mongolia Autonomous Region Mental Health Center or community hospital from September 21,2020 to December 16,2021 and fulfilling the International Classification of Sleep Disorders,third edition(ICSD-3)diagnostic criteria were enrolled.Additionally,16 age-and sex-matched healthy controls recruited from the community were set as control group.Patients were randomly divided into rTMS group and CBT-I group,25 cases in each group,and received rTMS or CBT-I intervention for 6 weeks respectively.At enrollment and completion of intervention,patients were subjected to Polysomnography(PSG),Pittsburgh Sleep Quality Index(PSQI),Insomnia Severity Index(ISI)and Repeatable Battery for the Assessment of Neuropsychological Status(RBANS).All participants underwent resting-state functional magnetic resonance imaging(rs-fMRI)scans,and amplitude of low-frequency fluctuation(ALFF)was calculated.The brain regions with statistically different ALFF values between patient group and control group were chosen as regions of interest(ROIs),and whole-brain seed-based functional connectivity analyses were conducted.Results After a 6-week intervention in the two groups,the main effect of time was significant for PSQI(F=41.160,P<0.05),ISI(F=69.615,P<0.05)and RBANS immediate memory(F=47.923,P<0.05),language(F=12.090,P<0.05)and delayed memory indices(F=28.193,P<0.05).A significant main effect of time for total sleep time(F=8.995,P<0.05),a significant main effect of time for sleep efficiency(F=12.414,P<0.05),a significant main effect of group for sleep efficiency(F=4.342,P<0.05)and a significant main effect of time for N1%(F=7.806,P<0.05)were observed.Sleep efficacy in CBT-I group improved significantly from pre-to post-test(t=-2.785,P<0.05).Patients in rTMS group showed increased functional connectivity between the orbital superior frontal gyrus and other regions including left lentiform nucleus putamen(t=4.991,P<0.05),right median cingulate and paracingulate gyri(t=4.471,P<0.05)and right postcentral gyrus(t=4.922,P<0.05),and increased functional connectivity between the orbital superior frontal gyrus and left middle frontal gyrus was found in CBT-I group(t=6.586,P<0.05).Conclusion rTMS and CBT-I may help alleviate insomnia and improve cognitive function of patients with chronic insomnia disorder.

Child ; Child, Preschool ; Dermatitis, Atopic ; blood ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Infant ; Male ; STAT3 Transcription Factor ; blood ; Signal Transduction ; Suppressor of Cytokine Signaling Proteins ; blood

ObjectiveTo investigate the analgesic effect of Tuina at the "Weizhong （BL 40）" on neuropathic pain in a rat model of chronic constriction injury （CCI） of the sciatic nerve and its potential central spinal mechanisms. MethodsThirty-two Sprague-Dawley rats were randomly divided into four groups （8 rats in each group）， sham-operated group， model group， Tuina group， and blockade group. The CCI model was established in the model group， Tuina group， and the blockade group by ligating the sciatic nerve with catgut， while the sham-operated group underwent only sciatic nerve exposure without ligation. From postoperative day 4 to day 14， rats in the Tuina group and the blockade group received Tuina manipulation at the "Weizhong （BL 40）" using a dynamic pressure distribution measurement system （5 N pressure， 2 Hz frequency， 10 min per session， once daily）. The blockade group also received intraperitoneal injections of the microglial inhibitor minocycline （10 mg/kg） once daily. The sham-operated and the model group underwent the same handling and fixation as the Tuina group without actual Tuina. Mechanical withdrawal threshold （MWT） and paw withdrawal latency （PWL） were measured before surgery and on day 3， 7， 10， and 14 post-surgery. Transmission electron microscopy was used to evaluate sciatic nerve injury and repair， measuring axon diameter and total myelinated fiber diameter to calculate the g-ratio. Western Blotting was performed to detect the protein levels of ionized calcium-binding adapter molecule 1 （Iba-1）， CD206， CD68， interleukin-10 （IL-10）， and β-endorphin （β-EP） precursor pro-opiomelanocortin （POMC） in the ipsilateral spinal dorsal horn. ResultsCompared with the sham-operated group， the model group showed significantly reduced MWT and PWL on day 3， 7， 10， and 14 （P＜0.01）. Compared with the model group， the Tuina group and the blockade group showed increased MWT and PWL on day 10 and 14 （P＜0.05）. Compared with the Tuina group， the blockade group exhibited higher MWT on day 7， 10， and 14， and higher PWL on day 10 （P＜0.05）. Sciatic nerve pathological morphology revealed intact and well-structured myelin in the sham-operated group， while the model group exhibited myelin collapse， distortion， and myelin ovoid formation. The Tuina group displayed partially irregular myelin with occasional myelin collapse， whereas the blockade group exhibited partial myelin irregularities and phospholipid shedding. Compared with the sham-operated group， the model group showed a decreased g-ratio and increased levels of Iba-1 and CD68 in the spinal dorsal horn （P＜0.05 or P＜0.01）. Compared with the model group， the Tuina group and the blockade group exhibited an increased g-ratio and reduced Iba-1 and CD68 levels. Additionally， the Tuina group showed elevated levels of CD206， IL-10， and POMC， whereas the blockade group had decreased CD206 levels （P＜0.05）. ConclusionTuina at "Weizhong （BL 40）" alleviates neuropathic pain in CCI rats， potentially by regulating microglial activation in the spinal cord， inhibiting M1 polarization while promoting M2 polarization， and activating the IL-10/β-EP pathway to exert analgesic effects.