The past, present and future of sleep medicine in China / 北京大学学报(医学版)

Sleep is a highly conserved phenomenon in endotherms, and has a universal physiological function across all species. In mammals, sleep can be divided into two stages: rapid eye movement (REM) sleep and non-REM (NREM) sleep, which alternate in a cyclic manner. Humans spend about one-third of their lives asleep. Sufficient sleep is necessary for humans to sustain everyday functioning. Sleep plays an important role in regulating energy metabolism, immune defense, endocrine function, and the consolidation of memory process. With the development of social economy and the change of life style, sleep duration of the residents has gradually decreased and the incidence of sleep disturbances has increased. Sleep disturbances can lead to severe mental disorders, such as depression, anxiety disorders, dementia, and other mental diseases, and may increase the risk of physical diseases, such as chronic inflammation, heart disease, diabetes, hypertension, atherosclerosis and others. Maintaining good sleep is of great significance for developing social productive forces, promoting sustainable development of economic society, and is a necessary condition for carrying out the "Healthy China Strategy". The sleep research in China started in 1950s. After decades of development, researchers have made great progress in the molecular mechanisms of sleep and wakefulness, the pathogenesis of sleep disorders and the development of new therapies. With the advancement of science and technology and the public's attention to sleep, the level of clinical diagnosis and therapy of sleep disorders in China is gradually brought in line with international standards. The publication of diagnosis and treatment guidelines in the field of sleep medicine will promote the standardization of the construction. In the future, it is still necessary to promote the development of sleep medicine in the following aspects: Strengthening the professional training and discipline construction, improving the cooperation of sleep research, promoting the intelligent diagnosis and treatment of sleep disorders, and developing the new intervention strategies. Therefore, this review will comprehensively summarize the origin, current situation, and future expectations of sleep medicine in China, including discipline construction of sleep medicine, the number of sleep project grants, research findings, the status and progress of diagnosis and treatment of sleep disorders, and the development direction of sleep medicine.

Exosomes in the Pathogenesis of Rheumatoid Arthritis / 中国医学科学院学报

Exosomes are 30-100 nm vesicles secreted from almost all types of cells.They contain various molecular constituents,including proteins,lipids,and RNA.As important mediators of cell-to-cell communication,exosomes are involved in a variety of physiological and pathological processes such as inflammatory reaction,cell proliferation and differentiation,tissue repair,immune signal transduction,and stress response.Exosomes can regulate and maintain the initiation and progression of many autoimmune diseases,especially rheumatoid arthritis.Meanwhile,exosomes may be a new biomarker for the diagnosis of rheumatoid arthritis and a potential treatment vector for this disease.

Zoledronic acid promotes dental implant osseointegration in osteoporosis / 中国组织工程研究

BACKGROUND: Zoledronic acid can effectively enhance dental implant osseointegration, but it can also impair soft tissue and blood supply around the implant, eventually leading to bisphosphonate-associated osteonecrosis of the jaw. Therefore, it is a problem highly valued in implant restorations. OBJECTIVE: To review the application of zoledronic acid in the dental implantation after osteoporosis. METHODS: The first author searched PubMed and CNKI using computer for relevant articles concerning the potential mechanism by which zoledronic acid promotes dental implant osseointegration as well as its application in vitro and in vivo. The key words were "bisphosphonate, zoledronic acid, implant, osseointegration" in English and Chinese, respectively. RESULTS AND CONCLUSION: Zoledronic acid has been demonstrated to inhibit bone resorption and promote bone formation via local or systemic use, single or combined use with other drugs. However, the inhibition of osteoclasts by zoledronic acid is associated with the dose and action time of zoledronic acid. Thus, further investigation on the specific mechanisms of zoledronic acid at different dose and with different action time are warranted. We should further elucidate the risk factors and determinants of osteonecrosis of the jaw through clinical studies, and then find effective approaches to reduce the risk of jaw osteonecrosis and to maximize the positive effect of zoledronic acid in the dental implantation.

Mechanism of GABA receptors involved in spasticity inhibition induced by transcranial magnetic stimulation following spinal cord injury / 华中科技大学学报（医学）（英德文版）

The effect of high-frequency repetitive transcranial magnetic stimulation (rTMS) on spasticity following spinal cord injury (SCI) and the action mechanism were investigated. SCI models were established in Sprague-Dawley rats. Five groups were set up: normal control group, SCI-7 day (7D) model group, SCI-14D model group, SCI-7D rTMS group and SCI-14D rTMS group (n=10 each). The rats in SCI rTMS groups were treated with 10 Hz rTMS at 8th day and 15th day after SCI respectively. Motor recovery and spasticity alleviation were evaluated by BBB scale once a week till the end of treatment. Finally, different parts of tissues were dissected out for detection of GABA receptors using Western blotting and polymerase chain reaction (PCR) technique. The results showed that the BBB scores after treatment were significantly higher in SCI-7D rTMS group than in SCI-14D rTMS group (P<0.05). The GABA receptors were down-regulated more significantly in SCI-14D model group than in SCI-7D model group (P<0.05). At different time points, rTMS treatment could affect the up-regulation of GABA receptors: The up-regulation of GABA receptors was more obvious in SCI-7D rTMS group than in SCI-14D rTMS treatment group (P<0.05). It was concluded that 10-Hz rTMS could alleviate spasticity following SCI and promote the motor recovery in rats, which might be attributed to the up-regulation of GABA receptors. It was also suggested that early high-frequency rTMS treatment after SCI may achieve more satisfactory curative effectiveness.

Repetitive magnetic stimulation promotes neural stem cells proliferation by upregulating MiR-106b in vitro / 华中科技大学学报（医学）（英德文版）

Neural stem cells (NSCs) proliferation can be influenced by repetitive transcranial magnetic stimulation (rTMS) in vivo via microRNA-106b-25 cluster, but the underlying mechanisms are poorly understood. This study investigated the involvement of microRNA-106b-25 cluster in the proliferation of NSCs after repetitive magnetic stimulation (rMS) in vitro. NSCs were stimulated by rMS (200/400/600/800/1000 pulses per day, with 10 Hz frequency and 50% maximum machine output) over a 3-day period. NSCs proliferation was detected by using ki-67 and EdU staining. Ki-67, p21, p57, cyclinD1, cyclinE, cyclinA, cdk2, cdk4 proteins and miR-106b, miR-93, miR-25 mRNAs were detected by Western blotting and qRT-PCR, respectively. The results showed that rMS could promote NSCs proliferation in a dose-dependent manner. The proportions of ki-67+ and Edu+ cells in 1000 pulses group were 20.65% and 4.00%, respectively, significantly higher than those in control group (9.25%, 2.05%). The expression levels of miR-106b and miR-93 were significantly upregulated in 600-1000 pulses groups compared with control group (P<0.05 or 0.01 for all). The expression levels of p21 protein were decreased significantly in 800/1000 pulses groups, and those of cyclinD1, cyclinA, cyclinE, cdk2 and cdk4 were obviously increased after rMS as compared with control group (P<0.05 or 0.01 for all). In conclusion, our findings suggested that rMS enhances the NSCs proliferation in vitro in a dose-dependent manner and miR-106b/p21/cdks/cyclins pathway was involved in the process.

Mechanism of GABA receptors involved in spasticity inhibition induced by transcranial magnetic stimulation following spinal cord injury / 华中科技大学学报（医学）（英德文版）

The effect of high-frequency repetitive transcranial magnetic stimulation (rTMS) on spasticity following spinal cord injury (SCI) and the action mechanism were investigated. SCI models were established in Sprague-Dawley rats. Five groups were set up: normal control group, SCI-7 day (7D) model group, SCI-14D model group, SCI-7D rTMS group and SCI-14D rTMS group (n=10 each). The rats in SCI rTMS groups were treated with 10 Hz rTMS at 8th day and 15th day after SCI respectively. Motor recovery and spasticity alleviation were evaluated by BBB scale once a week till the end of treatment. Finally, different parts of tissues were dissected out for detection of GABA receptors using Western blotting and polymerase chain reaction (PCR) technique. The results showed that the BBB scores after treatment were significantly higher in SCI-7D rTMS group than in SCI-14D rTMS group (P<0.05). The GABA receptors were down-regulated more significantly in SCI-14D model group than in SCI-7D model group (P<0.05). At different time points, rTMS treatment could affect the up-regulation of GABA receptors: The up-regulation of GABA receptors was more obvious in SCI-7D rTMS group than in SCI-14D rTMS treatment group (P<0.05). It was concluded that 10-Hz rTMS could alleviate spasticity following SCI and promote the motor recovery in rats, which might be attributed to the up-regulation of GABA receptors. It was also suggested that early high-frequency rTMS treatment after SCI may achieve more satisfactory curative effectiveness.

Effects of S100A4 expressed In white matter astrocytes on sensory neurite outgrowth in vitro / 中华物理医学与康复杂志

Objective To investigate the role of white matter astrocytes and their specific protein S100A4 in sensory neurite outgrowth in vitro.Methods White matter astrocyte cultures expressing S100A4 were prepared. Dissociated adult dorsal root ganglion(DRG)cells were placed on the top of the astrocytes and co-cultured for 6,12, 18,24 hours.Small interfering S100A4 RNA was used to eliminate S100A4 expression.The growth of DRG cell neu- rites on S100A4-sileneed and S100A4-expressing astrocytes was compared.Results 12,18 and 24 hours after the co-culture with S100A4-expressing or S100A4-silenced astroeytes,neurite growth from the DRG cells was observed. Neurite outgrowth was significantly greater in S100A4 siRNA treated cultures compared to control siRNA treated white matter astrocyte cultures.Conclusion These findings suggest that white matter astroeytes are able to support axonal regeneration and,furthermore,that administration of small interfering S100A4 RNA provides strong additional support for axon regeneration.

Effect of electroacupuncture on bFGF、Ang-2 and Tie-2 expression in rats with cerebral ischemia / 中华物理医学与康复杂志

Objective To observe the effect of electroacupuncture(EA) on the angiogenesis in rats with cerebral ischemia.Methods 30 male Wistar rats were randomly divided into 3 groups:normal group,model group and EA group.After the establishment of acute middle cerebral artery occlusion(MCAO),the rats were treated with EA on DU20 and DU26.Then the expression of bFGF,Ang-2 and Tie-2 by immunohistochemical staining was ob- served.Results The expression of bFGF and Ang-2 around the infarction locus of EA group increased remarkably compared with normal group and model group and the increase of Tie-2 was not significant.Conclusion EA can increase the expression of bFGF and Ang-2 around the infarction locus and promote the angiogenesis in rats with cere- bral ischemia.

The protective effects and mechanism of Green Tangerine induced hypertension and mild hypothermia on brain infarction during focal cerebral ischemia and reperfusion / 中华物理医学与康复杂志

Objective To investigate the protective effects of Green Tangerine induced hypertension and mild hypothermia on focal cerebral ischemia and reperfusion and local cerebral glucose utilization(LCGU)in the in- farction rim in rats.Methods A total of 64 rats were used and randomly divided into a control group,a Green Tan- gerine induced hypertension group,a mild hypothermia group and a combination therapy group.The neurologic defi- cits,infarct size and LCGU were observed in the rats with focal cerebral ischemia and reperfusion.Results Com- pared with the control group,the neurologic deficits(P