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Hemorrhagic transformation in patients with large-artery atherosclerotic stroke is associated with the gut microbiota and lipopolysaccharide

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Neural Regeneration Research 2024年第7期19卷 1532-1540页

作者： Qin Huang Minping Wei Xianjing Feng Yunfang Luo Yunhai Liu Jian Xia Department of Neurology Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Department of Neurology Peking University People’s HospitalBeijingChina clinical Research Center for Cerebrovascular Disease of Hunan province Central South UniversityChangshaHunan ProvinceChina National clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina

Hemorrhagic transformation is a major complication of large-artery atheroscle rotic stroke(a major ischemic stro ke subtype)that wo rsens outcomes and increases *** of the gut microbiota is an important feature of stroke,and some specific bacteria and bacterial metabolites may contribute to hemorrhagic transformation *** aimed to investigate the relationship between the gut microbiota and hemorrhagic transformation in largearte ry atheroscle rotic stro *** observational retrospective study was *** May 2020 to September 2021,blood and fecal samples were obtained upon admission from 32 patients with first-ever acute ischemic stroke and not undergoing intravenous thrombolysis or endovascular thrombectomy,as well as 16 healthy *** with stro ke who developed hemorrhagic transfo rmation(n=15)were compared to those who did not develop hemorrhagic transformation(n=17)and with healthy *** gut microbiota was assessed through 16S ribosomal ribonucleic acid *** also examined key components of the lipopolysaccharide pathway:lipopolysaccharide,lipopolysaccharide-binding protein,and soluble *** observed that bacterial diversity was decreased in both the hemorrhagic transformation and non-hemorrhagic transfo rmation group compared with the healthy *** patients with ischemic stro ke who developed hemorrhagic transfo rmation exhibited altered gut micro biota composition,in particular an increase in the relative abundance and dive rsity of members belonging to the Enterobacteriaceae *** lipopolysaccharide and lipopolysaccharide-binding protein levels were higher in the hemorrhagic transformation group compared with the non-hemorrhagic transfo rmation ***,lipopolysaccharide-binding protein,and soluble CD14 concentrations were associated with increased abundance of Enterobacte ***,the role of the gut microbiota in hemorrhagic transformation was evaluated using

关键词： gut microbiota hemorrhagic transformation inflammation lipopolysaccharide stroke

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Glymphatic system:a gateway for neuroinflammation

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Neural Regeneration Research 2024年第12期19卷 2661-2672页

作者： Kailu Zou Qingwei Deng Hong Zhang Changsheng Huang Department of Anesthesiology Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Xiangya School of Medicine Central South UniversityChangshaHunan ProvinceChina National clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina

The glymphatic system is a relatively recently identified fluid exchange and transpo rt system in the *** evidence indicates thatglymphatic function is impaired not only in central nervous system disorders but also in systemic *** diseases can trigger the inflammatory responses in the central nervous system,occasionally leading to sustained inflammation and functional disturbance of the central nervous *** review summarizes the current knowledge on the association between glymphatic dysfunction and central nervous system *** addition,we discuss the hypothesis that disease conditions initially associated with peripheral inflammation ove rwhelm the performance of the glymphatic system,thereby triggering central nervous system dysfun ction,chronic neuroinflammation,and *** research investigating the role of the glymphatic system in neuroinflammation may offer innovative therapeutic approaches for central nervous system disorders.

关键词： aquaporin-4 central nervous system disease cerebrospinal fluid chronic neuroinflammation glymphatic dysfunction neurodegeneration peripheral nerve injury perivascular space systemic disease vicious cycle

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p38 MAPK inhibitor SB202190 suppresses ferroptosis in the glutamate-induced retinal excitotoxicity glaucoma model

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Neural Regeneration Research 2024年第10期19卷 2299-2309页

作者： Lemeng Feng Chao Wang Cheng Zhang Wulong Zhang Weiming Zhu Ye He Zhaohua Xia Weitao Song National clinical Research Center for Geriatric Diseases Xiangya Hospital of Central South UniversityChangshaHunan ProvinceChina Eye Center of Xiangya Hospital Central South UniversityChangshaHunan ProvinceChina Hunan Key laboratory of Ophthalmology ChangshaHunan ProvinceChina

Glutamate excitotoxicity has been shown to play an important role in glaucoma, and glutamate can induce ferroptosis. The p38 mitogenactivated protein kinase(MAPK) pathway inhibitor SB202190 has a potential ability to suppress ferroptosis, and its downstream targets, such as p53, have been shown to be associated with ferroptosis. However, whether ferroptosis also occurs in retinal ganglion cells in response to glutamate excitotoxicity and whether inhibition of ferroptosis reduces the loss of retinal ganglion cells induced by glutamate excitotoxicity remain unclear. This study investigated ferroptosis in a glutamate-induced glaucoma rat model and explored the effects and molecular mechanisms of SB202190 on retinal ganglion cells. A glutamate-induced excitotoxicity model in R28 cells and an N-methyl-D-aspartate-induced glaucoma model in rats were used. In vitro experiments showed that glutamate induced the accumulation of iron and lipid peroxide and morphological changes of mitochondria in R28 cells, and SB202190 inhibited these changes. Glutamate induced the levels of p-p38 MAPK/p38 MAPK and SAT1 and decreased the expression levels of ferritin light chain, SLC7A11, and GPX4. SB202190 inhibited the expression of iron death-related proteins induced by glutamate. In vivo experiments showed that SB202190 attenuated N-methyl-D-aspartate-induced damage to rat retinal ganglion cells and improved visual function. These results suggest that SB202190 can inhibit ferroptosis and protect retinal ganglion cells by regulating ferritin light chain, SAT1, and SLC7A11/Gpx4 pathways and may represent a potential retina protectant.

关键词： ferroptosis glaucoma glutamate excitotoxicity p38 MAPK retinal ganglion cell SB202190

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P-aminobenzoic acid promotes retinal regeneration through activation of Ascl1a in zebrafish

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Neural Regeneration Research 2024年第8期19卷 1849-1856页

作者： Meihui He Mingfang Xia Qian Yang Xingyi Chen Haibo Li Xiaobo Xia Eye Center of Xiangya Hospital Central South UniversityChangshaHunan ProvinceChina Hunan Key laboratory of Ophthalmology ChangshaHunan ProvinceChina National clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina

The retina of zebrafish can regenerate completely after injury.M ultiple studies have demonstrated that metabolic alte rations occur during retinal damage;however to date no study has identified a link between metabolites and retinal regeneration of ***,we performed an unbiased metabolome sequencing in the N-methyl-D-aspartic acid-damaged retinas of zebrafish to demonstrate the metabolomic mechanism of retinal *** the differentially-ex pressed metabolites,we found a significant decrease in p-aminobenzoic acid in the N-methyl-D-aspartic acid-damaged retinas of ***,we investigated the role of p-aminobenzoic acid in retinal regeneration in adult *** rtantly,p-aminobenzoic acid activated Achaetescute complex-like 1a expression,thereby promoting Müller glia reprogramming and division,as well as Müller glia-derived progenitor cell ***,we eliminated folic acid and inflammation as downstream effectors of PABA and demonstrated that PABA had little effect on Müller glia *** together,these findings show that PABA contributes to retinal regeneration through activation of Achaetescute complex-like 1a expression in the N-methyl-Daspartic acid-damaged retinas of zebrafish.

关键词： Achaetescute complex-like 1a(Ascl1a) metabolomics Müller glia p-aminobenzoic acid(PABA) retina regeneration zebrafish

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Study on sex differences and potential clinical value of threedimensional computerized tomography pelvimetry in rectal cancer patients

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 773-786页

作者： Xiao-Cong Zhou Fei-Yue Ke Gaurav Dhamija Hao Chen Qiang Wang Department of Colorectal Surgery The Dingli Clinical Institute of Wenzhou Medical University(Wenzhou Central Hospital)Wenzhou 325000Zhejiang ProvinceChina Postgraduate Training Base Alliance of Wenzhou Medical University Wenzhou Central HospitalWenzhou 325000Zhejiang ProvinceChina School of International Studies Wenzhou Medical UniversityWenzhou 325000Zhejiang ProvinceChina Department of Radiology The Dingli Clinical Institute of Wenzhou Medical University(Wenzhou Central Hospital)Wenzhou 325000Zhejiang ProvinceChina

BACKGROUND Laparoscopic rectal cancer radical surgery is a complex procedure affected by various ***,the existing literature lacks standardized parameters for the pelvic region and soft tissues,which hampers the establishment of consistent *** To comprehensively assess 16 pelvic and 7 soft tissue parameters through computerized tomography(CT)-based three-dimensional(3D)reconstruction,providing a strong theoretical basis to address challenges in laparoscopic rectal cancer radical *** We analyzed data from 218 patients who underwent radical laparoscopic surgery for rectal cancer,and utilized CT data for 3D pelvic *** anatomical points were carefully marked and measured using advanced 3D modeling *** analyze the pelvic and soft tissue parameters,we emp-loyed statistical methods including paired sample t-tests,Wilcoxon rank-sum tests,and correlation *** The investigation highlighted significant sex disparities in 14 pelvic bone parameters and 3 soft tissue *** demonstrated larger measurements in pelvic depth and overall curvature,smaller measurements in pelvic width,a larger mesorectal fat area,and a larger anterior-posterior abdominal *** contrast,females exhibited wider pelvises,shallower depth,smaller overall curvature,and an increased amount of subcutaneous fat ***,there were no significant sex differences observed in certain parameters such as sacral curvature height,superior pubococcygeal diameter,rectal area,visceral fat area,waist circumference,and transverse abdominal *** The reconstruction of 3D CT data enabled accurate pelvic measurements,revealing significant sex differences in both pelvic and soft tissue *** study design offer potential in predicting surgical difficulties and creating personalized surgical plans for male rectal cancer patients with a potentially“difficult pelvis”,ultimately improving surgical ***

关键词： Computerized tomography Rectal cancer Three-dimensional reconstruction Pelvimetry Sex differences

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Activation of the wnt/β-catenin/CYP1B1 pathway alleviates oxidative stress and protects the blood-brain barrier under cerebral ischemia/reperfusion conditions

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Neural Regeneration Research 2024年第7期19卷 1541-1547页

作者： Xingyong Chen Nannan Yao Yanguang Mao Dongyun Xiao Yiyi Huang Xu Zhang Yinzhou Wang Department of Neurology Fujian Provincial HospitalShengli Clinical Medical College of Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Neurology Cangzhou Central HospitalCangzhouHebei ProvinceChina Fujian Academy of Medical Science FuzhouFujian ProvinceChina Key Testing laboratory of Fujian province FuzhouFujian ProvinceChina

Accumulating evidence suggests that oxidative stress and the Wnt/β-catenin pathway participate in stroke-induced disruption of the blood-brain ***,the potential links between them following ischemic stroke remain largely *** present study found that cerebral ischemia leads to oxidative stress and repression of the Wnt/β-catenin ***,Wnt/β-catenin pathway activation by the pharmacological inhibito r,TWS119,relieved oxidative stress,increased the levels of cytochrome P4501B1(CYP1B1)and tight junction-associated proteins(zonula occludens-1[ZO-1],occludin and claudin-5),as well as brain microvascular density in cerebral ischemia *** r,rat brain microvascular endothelial cells that underwent oxygen glucose deprivation/reoxygenation displayed intense oxidative stress,suppression of the Wnt/β-catenin pathway,aggravated cell apoptosis,downregulated CYP1B1and tight junction protein levels,and inhibited cell prolife ration and *** ofβ-catenin or knockdown ofβ-catenin and CYP1B1 genes in rat brain mic rovascular endothelial cells at least partly ameliorated or exacerbated these effects,*** addition,small interfering RNA-mediatedβ-catenin silencing decreased CYP1B1 expression,whereas CYP1B1 knoc kdown did not change the levels of glycogen synthase kinase 3β,Wnt-3a,andβ-catenin proteins in rat brain microvascular endothelial cells after oxygen glucose deprivatio n/***,the data suggest that CYP1B1 can be regulated by Wnt/β-catenin signaling,and activation of the Wnt/β-catenin/CYP1B1 pathway contributes to alleviation of oxidative stress,increased tight junction levels,and protection of the blood-brain barrier against ischemia/hypoxia-induced injury.

关键词： blood-brain barrier CYP1B1 oxidative stress oxygen glucose deprivation/reoxygenation tight junction vascular endothelial cells Wnt/β-catenin pathway β-catenin

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Structural and functional connectivity of the whole brain and subnetworks in individuals with mild traumatic brain injury:predictors of patient prognosis

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Neural Regeneration Research 2024年第7期19卷 1553-1558页

作者： Sihong Huang Jungong Han Hairong Zheng Mengjun Li Chuxin Huang Xiaoyan Kui Jun Liu Department of Radiology The Second Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Department of Computer Science Aberystwyth UniversityAberystwythCeredigionUK Shenzhen Institutes of Advanced Technology Chinese Academy of SciencesShenzhenGuangdong ProvinceChina School of Computer Science and Engineering Central South UniversityChangshaHunan ProvinceChina Department of Radiology Quality Control Center of Hunan ProvinceChangshaHunan ProvinceChina clinical Research Center for Medical Imaging of Hunan province ChangshaHunan ProvinceChina

Patients with mild traumatic brain injury have a diverse clinical presentation,and the underlying pathophysiology remains poorly *** resonance imaging is a non-invasive technique that has been widely utilized to investigate neuro biological markers after mild traumatic brain *** approach has emerged as a promising tool for investigating the pathogenesis of mild traumatic brain injury.G raph theory is a quantitative method of analyzing complex networks that has been widely used to study changes in brain structure and ***,most previous mild traumatic brain injury studies using graph theory have focused on specific populations,with limited exploration of simultaneous abnormalities in structural and functional *** that mild traumatic brain injury is the most common type of traumatic brain injury encounte red in clinical practice,further investigation of the patient characteristics and evolution of structural and functional connectivity is *** the present study,we explored whether abnormal structural and functional connectivity in the acute phase could serve as indicators of longitudinal changes in imaging data and cognitive function in patients with mild traumatic brain *** this longitudinal study,we enrolled 46 patients with mild traumatic brain injury who were assessed within 2 wee ks of injury,as well as 36 healthy ***-state functional magnetic resonance imaging and diffusion-weighted imaging data were acquired for graph theoretical network *** the acute phase,patients with mild traumatic brain injury demonstrated reduced structural connectivity in the dorsal attention *** than 3 months of followup data revealed signs of recovery in structural and functional connectivity,as well as cognitive function,in 22 out of the 46 ***,better cognitive function was associated with more efficient ***,our data indicated that small-worldness in the acute sta

关键词： cognitive function cross-section follow-up functional connectivity graph theory longitudinal study mild traumatic brain injury prediction small-worldness structural connectivity subnetworks whole brain network

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Therapeutic utility of human umbilical cord-derived mesenchymal stem cells-based approaches in pulmonary diseases:Recent advancements and prospects

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World Journal of Stem Cells 2024年第2期16卷 70-88页

作者： Min Meng Wei-Wei Zhang Shuang-Feng Chen Da-Rui Wang Chang-Hui Zhou Department of central laboratory Liaocheng People’s HospitalLiaocheng 252000Shandong ProvinceChina Department of clinical laboratory Liaocheng People’s HospitalLiaocheng 252000Shandong ProvinceChina

Pulmonary diseases across all ages threaten millions of people and have emerged as one of the major public health issues *** diverse disease con-ditions,the currently available approaches are focused on alleviating clinical symptoms and delaying disease progression but have not shown significant therapeutic effects in patients with lung *** umbilical cord-derived mesenchymal stem cells(UC-MSCs)isolated from the human UC have the capacity for self-renewal and multilineage ***,in recent years,these cells have been demonstrated to have unique advantages in the treatment of lung *** searched the Public clinical Trial Database and found 55 clinical trials involving UC-MSC therapy for pulmonary diseases,including coronavirus disease 2019,acute respiratory distress syndrome,bron-chopulmonary dysplasia,chronic obstructive pulmonary disease,and pulmonary *** this review,we summarize the characteristics of these registered clinical trials and relevant published results and explore in depth the challenges and opportunitiesfaced in clinical ***,the underlying mole-cular mechanisms involved in UC-MSC-based therapy for pulmonary diseases are also analyzed in *** brief,this comprehensive review and detailed analysis of these clinical trials can be expected to provide a scientific reference for future large-scale clinical application.

关键词： Pulmonary diseases Mesenchymal stem cells Human umbilical cord Cell therapy clinical trials

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Construction of a nomogram model to predict technical difficulty in performing laparoscopic sphincter-preserving radical resection for rectal cancer

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World Journal of Gastroenterology 2024年第18期30卷 2418-2439页

作者： Xiao-Cong Zhou Shi-Wei Guan Fei-Yue Ke Gaurav Dhamija Qiang Wang Bang-Fei Chen Medical University(Wenzhou central Hospital) Wenzhou 325000Zhejiang ProvinceChina Department of Hepatobiliary Surgery The Dingli Clinical Institute of Wenzhou Medical University(Wenzhou Central Hospital)Wenzhou 325000Zhejiang ProvinceChina Postgraduate Training Base Alliance of Wenzhou Medical University Wenzhou Central HospitalWenzhou 325000Zhejiang ProvinceChina School of International Studies Wenzhou Medical UniversityWenzhou Central HospitalWenzhou 325000Zhejiang ProvinceChina Department of Radiology The Dingli Clinical Institute of Wenzhou Medical University(Wenzhou Central Hospital)Wenzhou 325000Zhejiang ProvinceChina Department of Colorectal Surgery The Affiliated Zhejiang HospitalZhejiang University School of Medicine(Zhejiang Hospital)Hangzhou 310000Zhejiang ProvinceChina

BACKGROUND Colorectal surgeons are well aware that performing surgery for rectal cancer becomes more challenging in obese patients with narrow and deep pelvic ***,it is essential for colorectal surgeons to have a comprehensive understanding of pelvic structure prior to surgery and anticipate potential surgical *** To evaluate predictive parameters for technical challenges encountered during laparoscopic radical sphincter-preserving surgery for rectal *** We retrospectively gathered data from 162 consecutive patients who underwent laparoscopic radical sphincterpreserving surgery for rectal ***-dimensional reconstruction of pelvic bone and soft tissue parameters was conducted using computed tomography(CT)*** difficulty was categorized as either high or low,and multivariate logistic regression analysis was employed to identify predictors of operative difficulty,ultimately creating a *** Out of 162 patients,21(13.0%)were classified in the high surgical difficulty group,while 141(87.0%)were in the low surgical difficulty *** logistic regression analysis showed that the surgical approach using laparoscopic intersphincteric dissection,intraoperative preventive ostomy,and the sacrococcygeal distance were independent risk factors for highly difficult laparoscopic radical sphincter-sparing surgery for rectal cancer(P<0.05).Conversely,the anterior-posterior diameter of pelvic inlet/sacrococcygeal distance was identified as a protective factor(P<0.05).A nomogram was subsequently constructed,demonstrating good predictive accuracy(C-index=0.834).CONCLUSION The surgical approach,intraoperative preventive ostomy,the sacrococcygeal distance,and the anterior-posterior diameter of pelvic inlet/sacrococcygeal distance could help to predict the difficulty of laparoscopic radical sphincter-preserving surgery.

关键词： Nomogram Rectal cancer Laparoscopic operation Sphincter-preserving surgery Technical difficulty

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The MORC2 p.S87L mutation reduces proliferation of pluripotent stem cells derived from a patient with the spinal muscular atrophy-like phenotype by inhibiting proliferation-related signaling pathways

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Neural Regeneration Research 2024年第1期19卷 205-211页

作者： Sen Zeng Honglan Yang Binghao Wang Yongzhi Xie Ke Xu Lei Liu Wanqian Cao Xionghao Liu Beisha Tang Mujun Liu Ruxu Zhang Department of Neurology The Third Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Department of Neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina Department of Radiology The Third Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Health Management Center The Third Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Center for Medical Genetics&Hunan Key laboratory of Medical Genetics School of Life SciencesCentral South UniversityChangshaHunan ProvinceChina National clinical Research Center for Geriatric Disorders Central South UniversityChangshaHunan ProvinceChina Department of Cell Biology School of Life SciencesCentral South UniversityChangshaHunan ProvinceChina

Mutations in the microrchidia CW-type zinc finger protein 2(MORC2)gene are the causative agent of Charcot-Marie-Tooth disease type 2Z(CMT2Z),and the hotspot mutation p.S87L is associated with a more seve re spinal muscular atrophy-like clinical *** aims of this study were to determine the mechanism of the severe phenotype caused by the MORC2 p.S87L mutation and to explore potential treatment *** cells were isolated from urine samples from a spinal muscular atrophy(SMA)-like patient[MORC2 p.S87L),a CMT2Z patient[MORC2 p.Q400R),and a healthy control and induced to generate pluripotent stem cells,which were then differentiated into motor neuron precursor ***-generation RNA sequencing followed by KEGG pathway enrichment analysis revealed that differentially expressed genes involved in the PI3K/Akt and MAP K/ERK signaling pathways were enriched in the p.S87L SMA-like patient group and were significantly downregulated in induced pluripotent stem *** proliferation was observed in the induced pluripotent stem cells and motor neuron precursor cells derived from the p.S87L SMA-like patient group compared with the CMT2Z patient group and the healthy control.G0/G1 phase cell cycle arrest was observed in induced pluripotent stem cells derived from the p.S87L SMA-like ***2 p.S87Lspecific antisense oligonucleotides(p.S87L-ASO-targeting)showed significant efficacy in improving cell prolife ration and activating the PI3K/Akt and MAP K/ERK pathways in induced pluripotent stem *** r,p.S87L-ASO-ta rgeting did not rescue prolife ration of motor neuron precursor *** findings suggest that downregulation of the PI3K/Akt and MAP K/ERK signaling pathways leading to reduced cell proliferation and G0/G1 phase cell cycle arrest in induced pluripotent stem cells might be the underlying mechanism of the severe p.S87L SMA-like phenotype.p.S87L-ASO-targeting treatment can alleviate disordered cell proliferation in the early stag

关键词： antisense oligonucleotides cell cycle arrest Charcot-Marie-Tooth disease 2Z induced pluripotent stem cells MAPK/ERK PI3K/Akt proliferation spinal muscular atrophy-like

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