Obstructive sleep apnea (OSA) induces childhood cognitive impairment via chronic intermittent hypoxia (CIH), a process to which endoplasmic reticulum stress (ERS)-mediated apoptosis critically contributes. Nuclear factor erythroid 2-related factor 2 (NRF2) is widely recognized for its significant neuroprotective effects in various neurological diseases, yet its role in ERS-related apoptosis in prefrontal neurons under CIH remains unclear. This study investigated NRF2's impact both in vitro and in vivo. In CIH-exposed Pheochromocytoma 12 (PC12) cells, mimicking OSA-related neuronal injury, CIH significantly triggered ERS and subsequent apoptosis, evidenced by the upregulated protein levels of ERS markers (p-PERK, ATF4, CHOP) and apoptotic markers (Cleaved-Caspase-3). Additionally, the antioxidant system was activated, as shown by elevated mRNA levels of Nrf2, Hmox1, and Gclc and protein levels of NRF2, HO-1, and GCLC. Treatment with the NRF2 activator sulforaphane (SFN) reduced CIH-induced apoptosis by suppressing ERS signaling and enhancing Hmox1 mRNA and HO‑1 protein expression. Conversely, ML385 (a NRF2 inhibitor) resulted in opposite outcomes. In vivo, after 4 weeks of CIH exposure, mice demonstrated spatial memory and learning deficits in the behavior test. In the prefrontal cortex, histological examination revealed increased neuronal apoptosis, characterized by elevated Cleaved-Caspase-3 protein levels, alongside activation of the NRF2 pathway. Treatment with SFN alleviated cognitive impairment and neuronal apoptosis by inhibiting ERS signaling, while enhancing Hmox1 mRNA and HO‑1 protein expression. Conversely, treatment with a NRF2 inhibitor had the opposite effects. In summary, we demonstrate that NRF2 mitigates CIH-induced neuronal apoptosis by suppressing the PERK-ATF4-CHOP signaling cascade and augmenting HO-1 expression, thereby improving cognitive impairment.

High-sugar diets (HSD) represent a pervasive environmental stressor with significant health risks, yet the comparative toxicology and underlying molecular mechanisms of its impact on the central nervous system remain poorly understood. This study investigated the neurobehavioral toxicity of HSD and elucidated its mechanism of action, utilizing the invertebrate model Drosophila melanogaster to explore conserved physiological responses. Chronic exposure to a 20% HSD induced significant sleep impairment, a key neurobehavioral endpoint, characterized by reduced total sleep time and increased activity duration without affecting core circadian rhythmicity. Mechanistically, we identified a novel, indirect neurotoxic pathway originating in the gut, highlighting a conserved gut-brain axis. HSD exposure acted as a potent disruptor of gut homeostasis, inducing microbiota dysbiosis (notably decreasing Acetobacter aceti abundance) and triggering a robust intestinal inflammatory response, marked by the upregulation of pro-inflammatory cytokines Upd3 and Eiger (homologs of mammalian IL-6 and TNF-α). This peripheral immunotoxicity was causally linked to central neurochemical disruption, leading to significant neurotransmitter imbalances in the brain. Critically, targeting the initial site of toxicity-the gut-by genetically reducing Upd3 or Eiger expression specifically in intestinal epithelial cells was sufficient to rescue both the sleep deficits and the altered neurotransmitter profiles. Furthermore, ameliorating gut dysbiosis via dietary supplementation with A. aceti reversed the intestinal inflammation and normalized sleep behavior. These findings demonstrate that HSD exerts its neurobehavioral toxicity through a conserved gut-brain axis mechanism, where microbiota dysbiosis and intestinal inflammation drive central neurotransmitter dysregulation. This work highlights a critical toxicological pathway for dietary stressors with broad comparative and physiological relevance and identifies the gut inflammatory axis as a potential therapeutic target.

Background:Osteoarthritis (OA), the most prevalent form of arthritis, is swiftly emerging as a chronic health condition, that poses the primary cause of disability and significant socioeconomic burden. Despite its prevalence, effective therapeutic options for OA remain elusive. This study seeks to explore the therapeutic potential of edaravone (EDA), a FDA-approved free radical scavenger, in the context of OA development and to elucidate its underlying mechanisms. Methods:In vitro, oxidative stress models were induced by stimulating chondrocytes with t-butylhydroperoxide (TBHP); then, we investigated the influence of EDA on chondrocyte dysfunction, apoptosis, inflammatory responses and mitochondrial function in TBHP-treated chondrocytes, along with the underlying mechanisms. In vivo, destabilization of the medial meniscus (DMM) model was used to investigate the impact of EDA on OA progression. Nrf2 -/- mice were applied to determine the potential role of NRF2 as a target for EDA. Results:EDA notably alleviates chondrocyte dysfunction triggered by oxidative stress, safeguards chondrocytes from apoptosis and inflammatory responses, and preserves mitochondrial function and redox balance within chondrocytes. At the molecular level, EDA appears to halt the progression of OA by engaging and activating the nuclear factor erythroid 2-related factor 2 (NRF2) pathway, which is crucial for maintaining mitochondrial function and redox equilibrium. Notably, the protective effects of EDA on OA are abolished in Nrf2 -/- mice, underscoring the significance of the NRF2 signaling pathway in mediating EDA's therapeutic effects. Conclusion:EDA has the potential to mitigate chondrocyte degeneration, thereby slowing the progression of OA. Thus, EDA may represent a novel therapeutic agent for the treatment of OA, potentially expanding its clinical utility. The translational potential of this article:As a clinically licensed drug used for the treatment of neurological disorders, edaravone has shown promising therapeutic effects on OA development. Mechanistically, edaravone stabilized mitochondrial function and maintained redox homeostasis by activating NRF2 signaling pathway. The protective effects of edaravone against OA were verified in vivo and in vitro. These findings presented robust evidence for repurposing edaravone for the treatment of OA in clinic.

BACKGROUND:Intervertebral disc degeneration (IDD) is the predominant cause of low back pain (LBP), that leads to significant disability and imposes a substantial socioeconomic burden. Despite its prevalence, effective treatment for IDD has yet to be fully established. This study aimed to explore the therapeutic potential of quercitrin (QUE) in IDD development and to elucidate its underlying mechanisms. METHODS:In vitro, we investigated the effects of QUE on ECM metabolism, inflammatory response and pyroptosis in IL-1β-stimulated nucleus pulposus cells (NPCs), along with the potential mechanisms. In vivo, mice lumbar spinal instability (LSI) was established to determined the impact of QUE on IDD progression. RESULTS:QUE significantly alleviated inflammation and maintained the ECM homeostasis under IL-1β stimulation in NPCs. Moreover, QUE appeared to inhibit pyroptosis, which was closely related to intense inflammatory response. Notably, the protective effects of QUE were abrogated upon inhibition of TRIM31 activity, indicating that TRIM31 mediated pyroptosis suppression is crucial for the therapeutic effects of QUE. CONCLUSION:QUE plays an important role in alleviating pyroptosis and inflammation within NPCs, thereby slowing the progression of IDD. Therefore, QUE might emerge as a promising therapeutic candidate for IDD, holding the potential for clinical application in the future.

ObjectivesThe study aimed to explore the underlying mechanisms of OSA-related cognitive impairment by investigating the altered topology of brain white matter networks in children with OSA.MethodsGraph theory was used to examine white matter networks' network topological properties in 46 OSA and 31 non-OSA children. All participants underwent MRI, polysomnography, and cognitive testing. The effects of the obstructive apnea-hypopnea index (OAHI) on topological properties of white matter networks and network properties on cognition were studied using hierarchical linear regression. Mediation analyses were used to explore whether white matter network properties mediated the effects of OAHI on cognition.ResultsChildren with OSA had significantly higher assortativity than non-OSA children. Furthermore, OAHI was associated with the nodal properties of several brain regions, primarily in the frontal and temporal lobes. The relationship between OAHI and verbal comprehension index was mediated through clustering coefficients in the right temporal pole of the superior temporal gyrus.ConclusionsOSA affects the development of white matter networks in children's brains. Besides, the mediating role of white matter network properties between the OAHI and the verbal comprehension index provided neuroimaging evidence of impaired cognitive function in children with OSA.

ObjectiveObstructive Sleep Apnea (OSA) during pregnancy is characterized by intermittent hypoxia (IH) during sleep and will lead to the rise of oxidative stress in the fetal body. Pyroptosis, a type of inflammatory and programmable cell death mediated by Gasdermin D (GSDMD), plays a substantial role in oxygen deprivation’s contribution to neural system damage. Existing research shows that Nicotinamide Adenine Dinucleotide Phosphate (NADPH) plays a protective role in alleviating brain tissue pyroptosis. We speculate that exogenous NADPH may play a protective role in OSA during pregnancy.MethodsA model of GIH group was established to simulate the pathophysiological mechanisms of OSA during pregnant and AIR group was established by giving the same frequency. Sham group was established by injecting NS and the NADPH group was established and given exogenous NADPH. We utilized the Morris Water Maze to assess cognitive function impairment, Luxol Fast Blue (LBF) staining to confirm myelin sheath formation, TUNEL staining to examine cell death in fetal mice brain tissue, and Western blotting to detect pertinent protein expressions.ResultsThe GIH group offspring exhibited decreases in spatial learning and memory abilities, reduced numbers of oligodendrocytes and formed myelin, as well as increased expression of pyroptosis-related proteins. The NADPH group offspring showed restoration in spatial learning and memory abilities increased counts of oligodendrocytes and formed myelin sheaths, in addition to decreased expression of pyroptosis-related.ConclusionsThis study demonstrates that early injection of exogenous NADPH can alleviate the damage to fetal brain development caused by gestational intermittent hypoxia (GIH).

Objective: Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS) is a sleep respiratory disease associated with cognitive impairment, The nuclear factor erythroid 2 related factor 2 (Nrf2) plays a neuroprotective role. This study was designed to investigate the mechanism of Nrf2 protecting neural cells from endoplasmic reticulum stress (ERS), induced by chronic intermittent hypoxia (CIH) and sleep fragmentation (SF) which caused cognitive impairment in mice.Methods: Establishment of CIH and SF mice to simulate OSAHS mouse model. An eight-arm maze behavior test measured the cognitive function of mice, and Nissl staining and TUNEL staining were used to detect pathological changes in hippocampal neurons. The expression of ERS and Nrf2 and its downstream related mRNAs and proteins were detected by qRT-PCR and Western blotting.Results: CIH and SF lead to cognitive impairment in mice, and Sulforaphane (SFN, Nrf2 agonist) plays a protective role, while Nrf2-KO aggravates the cognitive impairment. CIH and SF reduced the number of Nissl bodies in neurons and induced apoptosis. The mRNA levels of BiP, CHOP, Nrf2, GCLC and Prdx1 in CIH, SF and CIH + SF groups were increased (p = 0.001), whereas the mRNA levels of BiP and CHOP in the CIH + SF + SFN group were decreased (p = 0.02) while those of Nrf2 and Prdx1 were increased (p = 0.005). The CIH + SF + Nrf2-KO group, the mRNA levels of CHOP were increased (p = 0.001) while Nrf2, GCLC and Prdx1 were decreased (p = 0.001). The protein levels of CHOP and active Caspase-12 in CIH, SF, CIH + SF and CIH + SF + Nrf2-KO groups were increased (p = 0.03), while those of Prdx1 and Nrf2 were increased (p = 0.03) in the CIH + SF + SFN group, while decreased (p = 0.02) in the Nrf2-KO group.Conclusions: Chronic intermittent hypoxia(CIH) and sleep fragmentation(SF) could aggravate the inflammatory response of nerve cells through endoplasmic reticulum stress, leading to apoptosis of nerve cells, and causing cognitive impairment in mice.Nrf2 alleviates cognitive impairment induced by chronic intermittent hypoxia and sleep fragmentation by modulating endoplasmic reticulum stress. Activation of Nrf2 protects cognitive impair-ment through the Nrf2-Prdx1 signaling pathway.

ObjectiveObstructive sleep apnea (OSA) seriously affects the children's cognitive functions, but the neuroimaging mechanism of cognitive impairment is still unclear. The purpose of our study was to explore the difference in brain local gray matter volume (GMV) between children with OSA and non-OSA, and the correlation between the difference regions of brain gray matter volume and cognitive, the severity of OSA.MethodEighty-three children aged 8–13 years were recruited in our study, 52 children were diagnosed as OSA by polysomnography, and 31 as the non-OSA. All the subjects were underwent high-resolution 3-dimensional T1-weighted magnetic resonance images. The voxel-based morphometry (VBM) was be used to analyse the local GMV. The Das-Naglieri cognitive assessment system (DN: CAS) was used to assess the subjects' cognitive. The difference of local GMV between the two groups was analyzed by two-sample T-test. The PSG variables and the scores of DN: CAS between the OSA group and non-OSA group were compared by independent samples t-tests. Pearson correlation was used to calculate the association between the difference areas of gray matter volumes in brain and DN: CAS scores, obstructive apnea/hypopnea index (OAHI, an index of the severity of OSA).ResultsThe gray matter volume of the right Middle Frontal Gyrus (MFG_R) in OSA children were larger than the non-OSA children, and the OSA children had lower scores of the Word Series in DN: CAS. There was negative correlation between the scores of Expressive Attention in DN: CAS and the gray matter volume of the right middle frontal gyrus, and it was no significantly correlation between OAHI and the gray matter volume of the right middle frontal gyrus.ConclusionOur results suggest that the development of gray matter volume in frontal cortex, which associated with attention, were sensitive to the effects of OSA, provides neuroimaging evidence for cognitive impairment in children with OSA.

目的:探讨阻塞性睡眠呼吸暂停(OSA)患儿的认知功能和脑白质网络改变以及两者之间的相关性.方法:收集2018年2月至2020年11月在温州医科大学附属第二医院育英儿童医院接受检查的7～13岁的年龄和性别相匹配的OSA患儿29例、健康对照组21例进行头部高分辨率3D T1WI和DTI扫描.计算每个参与者白质网络的全局属性(同配性)和节点属性(聚类系数、度中心性、局部效率)以及DN:CAS量表分,进行组间比较,并使用分层线性回归分析白质网络属性与认知得分之间的相关性.结果:未经过FDR校正时,OSA组右辅助运动区、右颞横回的度中心性和左中央后回、右颞横回的聚类系数以及左前扣带和旁扣带脑回、右颞横回的局部效率较健康对照组增加(P＜0.05);OSA组左眶部额中回、左舌回、左颞中回的度中心性和右颞中回的聚类系数以及右颞中回的局部效率较健康对照组降低(P＜0.05).左颞中回的度中心性与DN:CAS中的单词系列(β=0.421,P=0.015)、右颞中回的聚类系数(β=0.507,P=0.023)和局部效率(β=0.504,P=0.010)与同时性加工量表分呈正相关.结论:OSA患儿白质网络具有发生改变的趋势,其中颞中回的节点属性与认知有关,提示脑白质网络异常,特别是颞中回结构的改变,可能是OSA患儿认知损害的神经基础.

Background: Obstructive sleep apnea hypopnea syndrome (OSAHS) is one of the most common sleep disorders in childhood. It is characterized by frequent apnea and hypoventilation during sleep, leading to hypoxemia and sleep fragmentation that associated with cognitive impairment. However, there is currently a lack of effective instruments to assess cognitive impairment.Purpose: In this research, we aim to assess children’s cognitive function by Das-Naglieri cognitive assessment system (DN: CAS), investigate the serum Amyloid-β (Aβ) levels in OSAHS, and explore the correlation between cognitive function and serum Aβ level in OSAHS children.Methods: The recruited 118 children were divided into OSAHS and PS groups after all-night polysomnography, and an age-matched control group of 82 children underwent the study. The cognitive function of children was evaluated by DN: CAS and the serum Aβ level was measured by Enzyme-Linked Immunosorbent Assay (ELISA). ResultsIn our research, we found that children in the PS group presented lower scores in Planning than the control group, and those OSAHS children were subjected to reduced Full scale, Planning and Attention scores. The above scores in OSAHS group were negatively correlated with lowest blood oxygen saturation (LSaO2). In addition, the serum Aβ level in OSAHS group was significantly increased, negatively correlated with the Full score and Attention, and positively correlated with obstructive apnea-hypopnea index (OAHI).Conclusion: The DN: CAS could make a significant contribution to the clinical evaluation of cognition. Serum Aβ would be a potential biomarker for early diagnosis of cognitive impairment in children with OSAHS.

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is widely known for its multiple systems damage, especially neurocognitive deficits in children. Since their discovery, adenosine A2A receptors (A2ARs) have been considered as key elements in signaling pathways mediating neurodegenerative diseases such as Huntington's and Alzheimer's, as well as cognitive function regulation. Herein, we investigated A2AR role in cognitive impairment induced by chronic intermittent hypoxia (CIH). Mice were exposed to CIH 7 h every day for 4 weeks, and intraperitoneally injected with A2AR agonist CGS21680 or A2AR antagonist SCH58261 half an hour before IH exposure daily. The 8-arm radial arm maze was utilized to assess spatial memory after CIH exposures.To validate findings using pharmacology, the impact of intermittent hypoxia was investigated in A2AR knockout mice. CIH-induced memory dysfunction was manifested by increased error rates in the radial arm maze test. The behavioral changes were associated with hippocampal pathology, neuronal apoptosis, and synaptic plasticity impairment. The stimulation of adenosine A2AR exacerbated memory impairment with more serious neuropathological damage, attenuated long-term potentiation (LTP), syntaxin down-regulation, and increased BDNF protein. Moreover, apoptosis-promoting protein cleaved caspase-3 was upregulated while anti-apoptotic protein Bcl-2 was downregulated. Consistent with these findings, A2AR inhibition with SCH58261 and A2AR deletion exhibited the opposite result. Overall, these findings suggest that A2AR plays a critical role in CIH-induced impairment of learning and memory by accelerating hippocampal neuronal apoptosis and reducing synaptic plasticity. Blockade of adenosine A2A receptor alleviates cognitive dysfunction after chronic exposure to intermittent hypoxia in mice.

Caffeine has been used as a first-line drug for treatment of apnea neonatorum for decades due to its high safety and effectiveness. Studies report that caffeine mainly acts as a blocker of Adenosine Receptors (ARs). However, the mechanism of caffeine in reducing apnea neonatorum in the central nervous system has not been fully explored. Medial parabrachial nucleus (MPB) is part of the respiratory center of the pons that may be related to the activity of caffeine. Previous studies have not explored the effect and mechanism of caffeine on MPB neurons. To elucidate this, the current study used antagonists of A1 and A2a receptors to mimic the effect of caffeine in MPB of mice in vitro using the patch-clamp technique. The firing rates and spontaneous post-synaptic currents were recorded. The findings of the study showed that caffeine excited MPB neurons. Notably, the adenosine A1R antagonist 8-cyclopentyl-1,3-dimethyl-xanthine (CPT) but not the adenosine A2aR antagonist Istradefylline (KW6002) mimicked the exciting effect of caffeine, implying that caffeine excited MPB neurons in mice by blocking A1Rs. Further, the results indicated that caffeine could increase efficiency of synaptic transmission to excite MPB neurons. These findings suggest that A1Rs in MPB may be potential targets for caffeine in reducing apnea neonatorum.

目的 探讨肥胖儿童发生阻塞性睡眠呼吸暂停低通气综合征(OSAHS)的促炎和抗炎免疫调节失衡机制.方法 选取90例肥胖儿童,通过多导睡眠图睡眠监测,共确诊42例肥胖儿童合并OSAHS(肥胖OSAHS组),48例未合并OSAHS(肥胖非OSAHS组),另选取50例非肥胖健康儿童作为健康对照组.采用流式细胞术检测三组外周血T淋巴细胞亚群表达水平,ELISA法检测三组血清IFN-y、IL-4和IL-10的表达水平.结果 肥胖OSAHS组的行为表现、既往过敏性鼻炎史、父或母肥胖史、父或母打鼾史和睡眠相关症状发生率高于肥胖非OSAHS组和健康对照组(P＜0.05).与肥胖非OSAHS组和健康对照组比较,肥胖OSAHS组总睡眠时间、睡眠效率、最低血氧饱和度、深睡眠期占睡眠时间比和快动眼睡眠期占睡眠时间比降低(P＜0.01),而浅睡眠期占睡眠时间比、阻塞性呼吸暂停指数、睡眠呼吸紊乱指数和微觉醒指数增高(P＜0.01).与肥胖非OSAHS组和健康对照组比较,肥胖OSAHS组外周血中CD4+T淋巴细胞占比、IFN-γ和IL-4增高(P＜0.01),自然杀伤T细胞占比和IL-10降低(P＜0.01).结论 肥胖儿童发生OSAHS存在促炎和抗炎反应免疫失衡,IL-10抗炎的减弱可能是导致肥胖儿童发生OSAHS的重要原因.

Obstructive sleep apnea hypopnea syndrome (OSAHS) is associated with multiple system diseases. Neurocognitive dysfunction resulting from central nervous system complications has been reported, especially in children with OSAHS. Chronic intermittent hypoxia is accepted to be the major pathophysiological mechanism of OSAHS. Adenosine plays an important role in cellular function via interactions with its receptors. A2a receptor has been recognized as a factor involved in neuroprotection. However, the role of adenosine A2a receptor in intermittent hypoxia induced cellular injury is not completely understood. In this study, we aim to investigate the underlying mechanisms of A2a receptor mediated cellular damage caused by intermittent hypoxia in PC12 cells. We found that activated A2a receptor by CGS21680 decreased cellular viability, increased PKC as well as ATP-sensitive potassium channel (KATP) subunits expression Kir6.2 and SUR1. Inhibition of A2a receptor by SCH58261 increased cellular viability, suppressed PKC and SUR1 expression level, ultimately showing a protective role in PC12 cells. Moreover, we observed that CHE, which is an antagonist of PKC, downregulated Kir6.2 and SUR1 expression and increased cellular viability. Additionally, we found that A2a receptor activation induced cell injury was associated with increased Cleaved-Caspase 3 expression, which can be decreased by inhibition of A2a receptor or PKC. In conclusion, our findings indicate that A2a receptor induced KATP expression by PKC activation and plays a role in accelerating PC12 cells injury induced by intermittent hypoxia exposure via A2a-PKC-KATP signal pathway mediated apoptosis.

目的:探讨儿科住培新模式实施效果.方法:三级98名儿科住培医师为研究对象,进行问卷调查分析.结果:在核心工作能力的提升上,高年级住培医师明显强于低年资住培医师(P均＜0.05或＜α'=0.0167).结论:新模式使儿科住院医师专业素质和综合素养能力呈螺旋式上升,适合推广实施.

住院医师规范化培训(住培)是培养高水平专业人才的重要手段,是毕业后医学教育的重要组成部分.住院医师临床思维与决策能力的培养在住培阶段至关重要.我国部分住培基地仍采纳源自院校教育阶段以知识点传授作为教学活动目标的教学方法.目前亟需提高临床带教老师临床思维及决策能力的教学水平.文章将着重介绍住培阶段临床思维与决策能力的教学模式,旨在提高我国住培医师的临床诊疗水平.

Background: Xianyu decoction (XD), a Chinese experience recipe, shows inhibitory effects on lung cancer. However, the potential functions of XD on pneumonia were unknown. This study aimed to investigate the effect of XD on inflammatory response of childhood pneumonia. Methods: Human lung bronchial epithelial cell line BEAS-2B was cultured in different doses of LPS with or without XD treatment. The expression of miR-15a and IKBKB were altered by transfection assay. RT-PCR and western blot were used to evaluate the effects of XD and miR-15a mimic/ inhibitor on the expression levels of miR-15a, IKBKB, p65 and I kappa B alpha ELISA was used to determine the levels of CRP, IL-6 and IL-8. Results: High expression of miR-15a was observed in serum and cell model of pneumonia. miR-15a promoted the expression of inflammatory cytokines IL-6, IL-8, CRP and IKBKB in vitro. XD treatment downregulated the level of miR-15a in pneumonia children. In addition, XD reduced the expression of inflammatory cytokines and the phosphorylation levels of p65 and I kappa B alpha by inhibition of miR-15a and IKBKB expression in LPS-stimulated BEAS-2B cells. Conclusion: XD downregulated the level of miR-15a in serum of pneumonia children. Additionally, XD inhibited inflammatory response in LPS-stimulated BEAS-2B cells possibly by blocking IKBKB/NF-kappa B signal pathway which was regulated by miR-15a.

Obstructive sleep apnea hypopnea syndrome (OSAHS) is associated with the neurocognitive deficits as a result of the neuronal cell injury. Previous studies have shown that adenosine A1 receptor (ADORA1) played an important role against hypoxia exposure, such as controlling the metabolic recovery in rat hippocampal slices and increasing the resistance in the combined effects of hypoxia and hypercapnia. However, little is known about whether ADORA1 takes part in the course of neuronal cell injury after intermittent hypoxia exposure which was the main pathological characteristic of OSAHS. The present study is performed to explore the underlying mechanism of neuronal cell injury which was induced by intermittent hypoxia exposure in PC12 cells. In our research, we find that the stimulation of the ADORA1 by CCPA accelerated the injury of PC12 cells as well as upregulated the expression of PKC, inwardly rectifying potassium channel 6.2(Kir6.2) and sulfonylurea receptor 1(SUR1) while inhibition of the ADORA1 by DPCPX alleviated the injury of PC12 cells as well as downregulated the expression of PKC, Kir6.2, and SUR1. Moreover, inhibition of the PKC by CHE, also mitigated the injury of PC12 cells, suppressed the Kir6.2 and SUR1 expressions induced by PKC. Taken together, our findings indicate that ADORA1 accelerated PC12 cells injury after intermittent hypoxia exposure via ADORA1/PKC/KATP signaling pathway.

Objective: To study the clinical features and sleep-disordered breathing (SDB) in children with Pierre-Robin syndrome (PRS) to provide accurate diagnosis and treatment of PRS. Methods: Fifteen infants with Pierre-Robin syndrome admitted to the Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University from December 2014 to June 2016 were recruited in this study. A summary of the clinical characteristics, complications, and investigation of the prognosis by out-patient review or telephone follow-up was performed. Seven PRS children finished pediatric sleep questionnaires at 3 months old and eight children did it at 12 months old. Polysomnography (PSG) was monitored in 1 child. Results: Fifteen cases had typical clini-cal features of PRS including micrognathia, high arch palate, glossoptosis, and 3 had cleft palate. Thirteen cases developed dyspnea, 8 developed lung infection or aspiration pneumonia, and 6 developed feeding difficulties. The results of questionnaire survey show that 8 cases were screened positive for SDB at 3 months old, while 5 at 12 months old. Overnight PSG was performed in 1 case at 3 months and showed evidence of moderate OSAHS. The child with moderate obstructive sleep apnea underwent mandibular distraction osteogenesis at 4 months old. Twelve cases chose conservative treatment. Two cases failed to follow-up. Among 13 follow-up children, 5 died. In the 12th month of follow-up, the average weight of 8 cases was (8.0±1.5) kg, the average height was (72.0±3.0) cm. Conclusion: The PRS in children is associated with high risk for SDB. Timely diagnosis and proper treatment in children with PRS may help prevent long-term adverse sequelae.

我国住院医师规范化培训在上海、浙江等地取得了一定成绩,但仍存在较多问题.如何借鉴国际的成功经验,建设符合我国国情的儿科住院医师规范化培训模式,是目前亟待解决的问题.本研究介绍温州医科大学附属第二医院育英儿童医院2013年起借鉴美国成熟的儿科住院医师规范化培训经验,根据医院医疗教学资源及住院医师特点,通过制定儿科住院医师规范化培训的3年具体轮转计划和日常工作制度、完善质量监控体系、出台措施解决处方权、健全安全医疗制度.建立以“分层渐进、螺旋上升、项岗负责、强化督导”为特色的儿科住院医师规范化培训温州模式.新模式的4年实践,初见成效,达到为国家培养能在基层医疗单位独立从事临床工作的合格医师的目标.