Melatonin is widely used as an over-the-counter medication to treat insomnia in children with autism spectrum disorder (ASD) and neurogenetic disorders (NGD). However, there is still a lack of research on its efficacy and safety, and clinical practice standards are to be established. In response, the International Pediatric Sleep Association (IPSA) convened an expert panel and developed a consensus statement:"Melatonin Use in Managing Insomnia in Children with Autism and Other Neurogenetic Disorders-an Assessment by the International Pediatric Sleep Association (IPSA)", which was published in Sleep Medicine, April 2024. The consensus focused on the efficacy and adverse effects of melatonin treatment for insomnia in children with ASD and NGD-including Smith-Magenis syndrome, Rett syndrome, Angelman syndrome, and tuberous sclerosis complex. It systematically reviews randomized controlled trials (RCTs) conducted between 2012 and 2022, and integrates current best clinical practices to formulate 10 consensus recommendations. Despite these contributions, the consensus has limitations: a small number of included RCTs, a lack of grading for evidence quality, and recommendation strength. Furthermore, the study population is primarily composed of children from Western countries. This article seeks to interpret the consensus to improve standardized use of melatonin for insomnia in Chinese children with ASD and NGD, and to provide a reference for the future development of localized evidence-based guidelines.

Melatonin is widely used as an over-the-counter medication to treat insomnia in children with autism spectrum disorder (ASD) and neurogenetic disorders (NGD). However, there is still a lack of research on its efficacy and safety, and clinical practice standards are to be established. In response, the International Pediatric Sleep Association (IPSA) convened an expert panel and developed a consensus statement:"Melatonin Use in Managing Insomnia in Children with Autism and Other Neurogenetic Disorders-an Assessment by the International Pediatric Sleep Association (IPSA)", which was published in Sleep Medicine, April 2024. The consensus focused on the efficacy and adverse effects of melatonin treatment for insomnia in children with ASD and NGD-including Smith-Magenis syndrome, Rett syndrome, Angelman syndrome, and tuberous sclerosis complex. It systematically reviews randomized controlled trials (RCTs) conducted between 2012 and 2022, and integrates current best clinical practices to formulate 10 consensus recommendations. Despite these contributions, the consensus has limitations: a small number of included RCTs, a lack of grading for evidence quality, and recommendation strength. Furthermore, the study population is primarily composed of children from Western countries. This article seeks to interpret the consensus to improve standardized use of melatonin for insomnia in Chinese children with ASD and NGD, and to provide a reference for the future development of localized evidence-based guidelines.

Opioid analgesics are currently known as the best analgesics. However， toxicity and side effects such as constipation， tolerance and addiction severely limit their clinical application. With the in-depth understanding of the signal transduction mechanism of opioid receptors and the continuous advancement of drug design technology， researchers have managed to develop many promising new methods to get low-toxic and more efficient opioid analgesics， which are different from the traditional morphine skeleton structure modifications. This article focuses on three new research strategies of G-protein biased activation，“ one drug-multiple targets” and peripheral activation. The basic principles of relative separation of analgesic activity and adverse drug reaction by each strategy are introduced， and the latest research progress of representative drugs is briefly reviewed. Among them， the recently approved novel opioid analgesics oliceridine and tegileridine are G-protein biased μ-opioid receptor agonists， Cebranopadol is a typical “one drug-multiple targets” analgesic， and NFEPP is a representative drug of peripheral opioid receptor agonists. The above several strategies complement each other and provide reference for the development of new opioid analgesic drugs.

Transcranial direct current stimulation (tDCS) is a well-tolerated, safe and noninvasive physical brain stimulation method, which has been widely used in the treatment of some common mental disorders and neurological diseases and has achieved certain clinical effects. It is necessary to develop expert consensus on clinical treatment to improve the use norms in related fields. According to the clinical research published before August 2021 and the method of evidence-based medicine, we published an expert consensus on tDCS in the treatment of depressive disorders, schizophrenia, substance use-related disorders, obsessive-compulsive disorder, attention deficit hyperactivity disorder, autism, anxiety disorders, post-traumatic stress disorder, sleep disorders, pain, Parkinson′s disease, stroke, and epilepsy. The consensus also introduced the safety and efficacy of the clinical use of tDCS, and standardized the treatment process and operation technology, aiming to provide guidance for the clinical application of tDCS and promote the standardized development of this treatment technology in the future.

Transcranial direct current stimulation (tDCS) is a well-tolerated, safe and noninvasive physical brain stimulation method, which has been widely used in the treatment of some common mental disorders and neurological diseases and has achieved certain clinical effects. It is necessary to develop expert consensus on clinical treatment to improve the use norms in related fields. According to the clinical research published before August 2021 and the method of evidence-based medicine, we published an expert consensus on tDCS in the treatment of depressive disorders, schizophrenia, substance use-related disorders, obsessive-compulsive disorder, attention deficit hyperactivity disorder, autism, anxiety disorders, post-traumatic stress disorder, sleep disorders, pain, Parkinson′s disease, stroke, and epilepsy. The consensus also introduced the safety and efficacy of the clinical use of tDCS, and standardized the treatment process and operation technology, aiming to provide guidance for the clinical application of tDCS and promote the standardized development of this treatment technology in the future.

Objective: To evaluate the short-term effect of arthroscopic Endobutton combined with Orthocord suture fixation for tibia eminence fracture of anterior cruciate ligament in adults. Methods: The data of 9 adult patients with tibia eminence fracture of anterior cruciate ligament treated with Endobutton combined with Orthocord suture fixation from April 2017 to October 2018 were retrospectively analyzed. The range of motion of knee joint and the stability of knee joint were recorded 3 and 6 months after operation. Results: All patients were followed up for 3 and 6 months after operation. CT examination showed fracture reduction and healing 2 months after operation, and magnetic resonance image examination showed good anterior cruciate ligament tension 3 months after operation. The range of motion of knee joint was 0°-130° after 3 and 6 months, and Lanchman test was negative. The Lysholm score was (45.2 ± 6.7) scores, and IKDC score was (55.1 ± 7.3) scores before operation. The Lysholm score was (89.1 ± 7.2) scores, IKDC score was(87.4 ± 6.1) scores, Lysholm score was (95.4 ± 6.5) scores and IKDC score was (93.2 ± 7.8) scores at 6 months after operation. Conclusions Endobutton combined with Orthocord suture fixation under arthroscopy has a good short-term effect in the treatment tibia eminence fracture of anterior cruciate ligament in adults.

Objective To investigate the changes in the expression levels of miR-21 and its regulatory proteins in bone tissues of osteoporotic mouse model, and its correlation with bone mineral density. Methods Thirty ovariectomized (ovx) female mice were randomly divided into six groups according to different observation time (0 week, 1 week, 2 weeks, 4 weeks, 6 weeks, and 8 weeks, respectively). Smad7 expression level in the tissues of the distal femur of these mice was immunohistochemically analyzed. Real time PCR was performed at different time points for detecting changes in the mRNA levels of miR-21 and Smad7 target genes in the bone tissue. Dual-energy X-ray absorptiometry (DXA) was used to measure the distal femoral bone density in mice of each group. Results Immunohistochemical study revealed that the expression of Smad7 in the bone tissue of osteoporostic mouse gradually increased over time. Real time PCR analysis showed that the expression of mi R-21 gradually decreased, whereas the expression of Smad7 gradually increased. Over time, the bone density of mice gradually decreased, indicating that miR-21 was positively correlated with bone density, whereas Smad7 was negatively correlated with bone density. Conclusion Bone density of the osteoporotic mice gradually decreases. The expression of miR-21 is positively correlated with bone density, while that of Smad7 is negatively correlated with bone density.

Objective To evaluate the effect of conversion from mycophenolic acid (MPA) to mizoribine (MZR) in renal transplant recipients with gastrointestinal tract (GI) symptoms.Methods A total of 355 renal transplant recipients with GI symptoms caused by MPA administration were enrolled from April 2015 to March 2017 in 25 different renal transplant centers in China.The symptomatic improvement of GI before (baseline) and after conversion to MZR (1,2,4 weeks) was assessed by each item of GI symptoms indication.In addition,the efficacy and safety of the conversion therapy during 12 months were determined.Results Patients showed improvement in GI symptoms including diarrhea,abdominal pain,abdominal distention and stomachache after conversion to MZR 1,2,4 weeks (P＜0.05).In patients with different severity of diarrhea,conversion to MZR therapy significantly improved diarrhea (P＜0.05).During 12 months,no patient experienced clinical immune rejection.We did not observe any infections,leucopenia and other serious side effects.Conclusion MZR could markedly improve GI symptoms caused by MPA administration in renal transplant recipients.

[ ABSTRACT] AIM:To explore whether IL-1βinhibits the oligodendrocyte precursor cell ( OPCs) differentiation and affects axonal myelination.METHODS:One-day-old SD rats were randomly divided into control group and LPS group ( 48 rats in each group) .The rats in LPS group were intraperitoneally injected with 1 mg/kg LPS.The rats in control group were injected with an equal volume of PBS.The rats in each group were further divided into 3 h, 24 h, 3 d, 7 d, 14 d and 28 d subgroups after injection.The expression of IL-1βand IL-1R1 in the rat corpus callosum at 3 h, 24 h, 3 d, 7 d was determined by double immunofluorescence and Western blotting.The myelin basic protein( MBP) expression in the rat cor-pus callosum at 14 d, 28 d after injection was also measured.In vitro, primary OPCs culture was performed and divided in-to control group, 30 μg/L IL-1βgroup, 30 μg/L IL-1β+IL-1Ra group and 30 μg/L IL-1Ra group.The expression of MBP in the OPCs induced differentiation for 3 d was observed by double immunofluorescence and Western blotting.RE-SULTS:The expression of IL-1βand IL-1R1 in the rat corpus callosum at 3 h, 24 h, 3 d, 7 d after LPS injection was ob-viously increased and the expression of MBP in the rat corpus callosum at 14 d, 28 d in LPS group was obviously decreased compared with control group in vivo.The level of MBP was significantly decreased after IL-1βtreatment for 3 d in vitro. However, IL-1Ra (IL-1R inhibitor) reversed the down-regulation of MBP expression.IL-1βinhibited the expression of p-ERK, ERK over-expression reversed the down-regulation of MBP expression compared with IL-1βgroup.CONCLUSION:IL-1βinhibits the differentiation of OPCs, which may be involved in ERK pathways, thus leading to axonal hypomyelination in the corpus callosum of septic neonatal rats.

Objective To study the relationship between the expression of inducible nitric oxide synthase(iNOS)and neural cell apoptosis after chronic cauda equina compression. Methods Totally 30 male adult SD rats were randomly divided into 2 groups as the control group and the experi?mental group. The control group received sham operation with single laminectomy of L5 lumina. In the experimental group,the silicon sheet was in?serted into the spinal canal of L4 to cause single level compression of cauda equina. The L4 level of spinal cords were harvested at 2 weeks,4 weeks,8 weeks,and 12 weeks after operation in the experimental group,and at 4 weeks in the control group respectively,and then immunohistochemistry and image analysis were performed to observe the expression of iNOS in spinal cord and the TUNEL method was applied to observe cell apoptosis. The morphology of cells was observed by transmission electron microscope. Results There was few amount of iNOS expressed in the control group. The expression of iNOS was slight at 4 weeks in the experimental group and was higher at 8 weeks and 12 weeks compared with the control group. Small amount of neural cell apoptosis was evidenced in the control group,while neuron apoptosis appeared remarkably in the experimental group since 4 weeks and increased with the extension of time. Transmission electron microscopy found apoptosis changes in neurons in the experimental group. Conclusion The expression of iNOS increases in corresponding spinal cords after chronic compression of cuada equine and neural cell apoptosis oc?curs,indicating that iNOS is positively correlated with neural cell apoptosis.