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Identification of four differentially expressed genes associated with acute and chronic spinal cord injury based on bioinformatics data

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Neural Regeneration Research 2021年第5期16卷 865-870页

作者： su-ping niu Ya-Jun Zhang Na Han Xiao-Feng Yin Dian-Ying Zhang Yu-Hui Kou Key Laboratory of Trauma and Neural Regeneration(Peking University) Ministry of EducationBeijingChina Department of Trauma and Orthopedics Peking University People’s HospitalBeijingChina Trauma Medicine Center Peking University People’s HospitalBeijingChina Office of Academic Research Peking University People’s HospitalBeijingChina

Complex pathological changes occur during the development of spinal cord injury(SCI),and determining the underlying molecular events that occur during SCI is necessary for the development of promising molecular targets and therapeutic *** study was designed to explore differentially expressed genes(DEGs)associated with the acute and chronic stages of SCI using bioinformatics *** expression profiles(GSE45006,GSE93249,and GSE45550)were downloaded from the Gene Expression Omnibus ***-associated DEGs from rat samples were identified,and Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were *** addition,a protein-protein interaction network was *** 66 DEGs were identified in GSE45550 between 3–14 days after SCI,whereas 2418 DEGs were identified in GSE450061–56 days after ***,1263,195,and 75 overlapping DEGs were identified between these two expression profiles,3,7/8,and 14 days after SCI,***,16 overlapping DEGs were obtained in GSE450061–14 days after SCI,including Pank1,Hn1,Tmem150c,Rgd1309676,Lpl,Mdh1,Nnt,Loc100912219,Large1,Baiap2,Slc24a2,Fundc2,Mrps14,Slc16a7,Obfc1,and ***,3882 overlapping DEGs were identified in GSE932491–6 months after SCI,including 3316 protein-coding genes and 567 long non-coding RNA genes.A comparative analysis between GSE93249 and GSE45006 resulted in the enrichment of 1135 overlapping *** significant functions of these 1135 genes were correlated with the response to the immune effector process,the innate immune response,and cytokine ***,the biological processes and KEGG pathways of the overlapping DEGs were significantly enriched in immune system-related pathways,osteoclast differentiation,the nuclear factor-κB signaling pathway,and the chemokine signaling ***,an analysis of the overlapping DEGs associated with both acute and chronic SCI,assessed using the expressio

关键词： bioinformatics differential expression factor gene immune response injury pathways protein spinal cord

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Changes in proteins related to early nerve repair in a rat model of sciatic nerve injury

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Neural Regeneration Research 2021年第8期16卷 1622-1627页

作者： Yu-Song Yuan Fei Yu Ya-Jun Zhang su-ping niu Hai-Lin Xu Yu-Hui Kou Department of Trauma and Orthopedics Peking University People’s HospitalBeijingChina Key Laboratory of Trauma and Neural Regeneration(Peking University) Ministry of EducationBeijingChina National&Local Joint Engineering Research Center of Orthopedic Biomaterials Department of Bone&Joint SurgeryPeking University Shenzhen HospitalShenzhenGuangdong ProvinceChina National Center for Trauma Medicine BeijingChina Office of Academic Research Peking University People’s HospitalBeijingChina Diabetic Foot Treatment Center Peking University People’s HospitalBeijingChina

Peripheral nerves have a limited capacity for self-repair and those that are severely damaged or have significant defects are challenging to repair. Investigating the pathophysiology of peripheral nerve repair is important for the clinical treatment of peripheral nerve repair and regeneration. In this study, rat models of right sciatic nerve injury were established by a clamping method. Protein chip assay was performed to quantify the levels of neurotrophic, inflammation-related, chemotaxis-related and cell generation-related factors in the sciatic nerve within 7 days after injury. The results revealed that the expression levels of neurotrophic factors(ciliary neurotrophic factor) and inflammationrelated factors(intercellular cell adhesion molecule-1, interferon γ, interleukin-1α, interleukin-2, interleukin-4, interleukin-6, monocyte chemoattractant protein-1, prolactin R, receptor of advanced glycation end products and tumor necrosis factor-α), chemotaxis-related factors(cytokine-induced neutrophil chemoattractant-1, L-selectin and platelet-derived growth factor-AA) and cell generation-related factors(granulocyte-macrophage colony-stimulating factor) followed different trajectories. These findings will help clarify the pathophysiology of sciatic nerve injury repair and develop clinical treatments of peripheral nerve injury. This study was approved by the Ethics Committee of Peking University People's Hospital of China(approval No. 2015-50) on December 9, 2015.

关键词： animal model cell generation chemotaxis clamp injury inflammation injury neurotrophic factor peripheral nerve protein array repair sciatic nerve Wallerian degeneration

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Combining CUBIC Optical Clearing and Thy1-YFP-16 Mice to Observe Morphological Axon Changes During Wallerian Degeneration

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Current Medical Science 2021年第5期41卷 944-952页

作者： Yu-song YUAN Fei YU su-ping niu Hao LU Yu-hui KOU Hai-lin XU Department of Trauma and Orthopaedics Peking University People's HospitalPeking University'Beijing 100044China National and Local Joint Engineering Research Center of Orthopaedic Biomaterials Department of Bone&Joint SurgeryPeking University Shenzhen HospitalShenzhen 518036China Key Laboratory of Trauma and Neural Regeneration(Peking University) Ministry of EducationBeijing 100044China Office of Academic Research Peking University People's HospitalPeking UniversityBeijing 100044China Diabetic Foot Treatment Center Peking University People's HospitalPeking University'Beijing 100044China

Objective:Wallerian degeneration is a pathological process closely related to peripheral nerve regeneration following injury,and includes the disintegration and phagocytosis of peripheral nervous system ***,morphological changes are observed by performing immunofluorescence staining after sectioning,which results in the loss of some histological *** purpose of this study was to explore a new,nondestmetive,and systematic method for observing axonal histological changes during Wallerian ***:Thirty male Thy1-YFP-16 mice(SPF grade,6 weeks old,20±5 g)were randomly selected and divided into clear,unobstructed brain imaging cocktails and computational analysis(CUBIC)optical clearing(n=15)and traditional method groups(n=15).Five mice in each group were sacrificed at 1st,3rd,and 5th day following a crush *** histological axon changes were observed by CUBIC light optical clearing treatment,direct tissue section imaging,and HE ***:The results revealed that,compared with traditional imaging methods,there was no physical damage to the samples,which allowed for three-dimensional and deep-seated tissue imaging through *** image information could be nicely obtained by direct fluorescence imaging and HE staining,but it was difficult to obtain image information of the entire *** the same time,the image information obtained by fluorescence imaging and HE staining was partially ***:The combining of CUBIC and Thy1-YFP transgenic mice allowed for a clear and comprehensive observation of histological changes of axons in Wallerian degeneration.

关键词： Wallerian degeneration axon optical clearing clear,unobstructed brain imaging cocktails and computational analysis Thy1-YFP transgenic mice

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Intraoperative single administration of neutrophil peptide 1 accelerates the early functional recovery of peripheral nerves after crush injury

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Neural Regeneration Research 2020年第11期15卷 2108-2115页

作者： Yu-Song Yuan su-ping niu Fei Yu Ya-Jun Zhang Na Han Hao Lu Xiao-Feng Yin Hai-Lin Xu Yu-Hui Kou Department of Trauma and Orthopedics Peking University People’s HospitalPeking UniversityBeijingChina Key Laboratory of Trauma and Neural Regeneration(Peking University) Ministry of EducationBeijingChina Office of Academic Research Peking University People’s HospitalBeijingChina National and Local Joint Engineering Research Center of Orthopaedic Biomaterials Department of Bone&Joint SurgeryPeking University Shenzhen HospitalShenzhenGuangdong ProvinceChina National Center for Trauma Medicine BeijingChina Diabetic Foot Treatment Center Peking University People’s HospitalPeking UniversityBeijingChina

Neutrophil peptide 1 belongs to a family of peptides involved in innate immunity. Continuous intramuscular injection of neutrophil peptide 1 can promote the regeneration of peripheral nerves, but clinical application in this manner is not convenient. To this end, the effects of a single intraoperative administration of neutrophil peptide 1 on peripheral nerve regeneration were experimentally observed. A rat model of sciatic nerve crush injury was established using the clamp method. After model establishment, a normal saline group and a neutrophil peptide 1 group were injected with a single dose of normal saline or 10 μg/mL neutrophil peptide 1, respectively. A sham group, without sciatic nerve crush was also prepared as a control. Sciatic nerve function tests, neuroelectrophysiological tests, and hematoxylin-eosin staining showed that the nerve conduction velocity, sciatic functional index, and tibialis anterior muscle fiber cross-sectional area were better in the neutrophil peptide 1 group than in the normal saline group at 4 weeks after surgery. At 4 and 8 weeks after surgery, there were no differences in the wet weight of the tibialis anterior muscle between the neutrophil peptide 1 and saline groups. Histological staining of the sciatic nerve showed no significant differences in the number of myelinated nerve fibers or the axon cross-sectional area between the neutrophil peptide 1 and normal saline groups. The above data confirmed that a single dose of neutrophil peptide 1 during surgery can promote the recovery of neurological function 4 weeks after sciatic nerve injury. All the experiments were approved by the Medical Ethics Committee of Peking University People's Hospital, China(approval No. 2015-50) on December 9, 2015.

关键词： crush injury defensin 1 gait analysis intraoperative administration nerve conduction velocity nervous system neutrophil peptide 1 peripheral nerve injury peripheral nerve regeneration sciatic nerve tibialis anterior muscle trauma

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Repair of long segmental ulnar nerve defects in rats by several different kinds of nerve transposition

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Neural Regeneration Research 2019年第4期14卷 692-698页

作者： Fei Yu You-Lai Yu su-ping niu Pei-Xun Zhang Xiao-Feng Yin Na Han Ya-Jun Zhang Dian-Ying Zhang Yu-Hui Kou Bao-Guo Jiang Peking University People's Hospital The Affiliated Hospital of Xuzhou Medical University

Multiple regeneration of axonal buds has been shown to exist during the repair of peripheral nerve injury, which confirms a certain repair potential of the injured peripheral nerve. Therefore, a systematic nerve transposition repair technique has been proposed to treat severe peripheral nerve injury. During nerve transposition repair, the regenerated nerve fibers of motor neurons in the anterior horn of the spinal cord can effectively grow into the repaired distal nerve and target muscle tissues, which is conducive to the recovery of motor function. The aim of this study was to explore regeneration and nerve functional recovery after repairing a long-segment peripheral nerve defect by transposition of different donor nerves. A long-segment(2 mm) ulnar nerve defect in Sprague-Dawley rats was repaired by transposition of the musculocutaneous nerve, medial pectoral nerve, muscular branches of the radial nerve and anterior interosseous nerve(pronator quadratus muscle branch). In situ repair of the ulnar nerve was considered as a control. Three months later, wrist flexion function, nerve regeneration and innervation muscle recovery in rats were assessed using neuroelectrophysiological testing, osmic acid staining and hematoxylin-eosin staining, respectively. Our findings indicate that repair of a long-segment ulnar nerve defect with different donor nerve transpositions can reinnervate axonal function of motor neurons in the anterior horn of spinal cord and restore the function of affected limbs to a certain extent.

关键词： nerve regeneration nerve transposition repair conical sleeve small gap sleeve bridging ulnar nerve target organ muscle nerve reinnervation neural regeneration

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Reinnervation of spinal cord anterior horn cells after median nerve repair using transposition with other nerves

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Neural Regeneration Research 2019年第4期14卷 699-705页

作者： Yu-Song Yuan su-ping niu You-Lai Yu Pei-Xun Zhang Xiao-Feng Yin Na Han Ya-Jun Zhang Dian-Ying Zhang Hai-Lin Xu Yu-Hui Kou Bao-Guo Jiang Peking University People's Hospital The Affiliated Hospital of Xuzhou Medical University

Our previous studies have confirmed that during nerve transposition repair to injured peripheral nerves, the regenerated nerve fibers of motor neurons in the anterior horn of the spinal cord can effectively repair distal nerve and target muscle tissue and restore muscle motor function. To observe the effect of nerve regeneration and motor function recovery after several types of nerve transposition for median nerve defect(2 mm), 30 Sprague-Dawley rats were randomly divided into sham operation group, epineurial neurorrhaphy group, musculocutaneous nerve transposition group, medial pectoral nerve transposition group, and radial nerve muscular branch transposition group. Three months after nerve repair, the wrist flexion test was used to evaluate the recovery of wrist flexion after regeneration of median nerve in the affected limbs of rats. The number of myelinated nerve fibers, the thickness of myelin sheath, the diameter of axons and the cross-sectional area of axons in the proximal and distal segments of the repaired nerves were measured by osmic acid staining. The ratio of newly produced distal myelinated nerve fibers to the number of proximal myelinated nerve fibers was calculated. Wet weights of the flexor digitorum superficialis muscles were measured. Muscle fiber morphology was detected using hematoxylin-eosin staining. The cross-sectional area of muscle fibers was calculated to assess the recovery of muscles. Results showed that wrist flexion function was restored, and the nerve grew into the distal effector in all three nerve transposition groups and the epineurial neurorrhaphy group. There were differences in the number of myelinated nerve fibers in each group. The magnification of proximal to distal nerves was 1.80, 3.00, 2.50, and 3.12 in epineurial neurorrhaphy group, musculocutaneous nerve transposition group, medial pectoral nerve transposition group, and radial nerve muscular branch transposition group, respectively. Nevertheless, axon diameters of new

关键词： nerve regeneration transposition repair median nerve functional remodeling muscle atrophy surgical intervention peripheral nerve injury neural regeneration

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Local administration of icariin contributes to peripheral nerve regeneration and functional recovery

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Neural Regeneration Research 2015年第1期10卷 84-89页

作者： Bo Chen su-ping niu Zhi-yong Wang Zhen-wei Wang Jiu-xu Deng Pei-xun Zhang Xiao-feng Yin Na Han Yu-hui Kou Bao-guo Jiang Department of Trauma and Orthopedics Peking University People’s Hospital Beijing Shijitan Hospital Capital Medical University Health Science Center Peking University

Our previous study showed that systemic administration of the traditional Chinese medicine Epimedium extract promotes peripheral nerve regeneration. Here, we sought to explore the ther- apeutic effects of local administration of icariin, a major component of Epimedium extract, on peripheral nerve regeneration. A poly（lactic-co-glycolic acid） biological conduit sleeve was used to bridge a 5 mm right sciatic nerve defect in rats, and physiological saline, nerve growth factor, icariin suspension, or nerve growth factor-releasing microsphere suspension was injected into the defect. Twelve weeks later, sciatic nerve conduction velocity and the number of myelinated fibers were notably greater in the rats treated with icariin suspension or nerve growth factor-releasing microspheres than those that had received nerve growth factor or physiological saline. The effects of icariin suspension were similar to those of nerve growth factor-releasing microspheres. These data suggest that icariin acts as a nerve growth factor-releasing agent, and indicate that local ap- plication of icariin after spinal injury can promote peripheral nerve regeneration.

关键词： nerve regeneration peripheral nerve sciatic nerve traditional Chinese medicine icariin sleeve bridging suture nerve growth factor NSFC grants neural regeneration

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Clinical effects of phospholipase D2 in attenuating acute pancreatitis

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World Journal of Gastroenterology 2025年第2期31卷 52-60页

作者： Jin-Wei niu Guo-Chao Zhang Wu Ning Hai-Bin Liu Hua Yang Chao-Feng Li Department of General surgery China-Japan Friendship HospitalBeijing 100029China

BACKGROUND The objective of the current study was to elucidate the clinical mechanism through which phospholipase D2(PLD2)exerted a regulatory effect on neutrophil migra-tion,thereby alleviating the progression of acute *** To elucidate the clinical mechanism through which PLD2 exerted a regulatory effect on neutrophil migration,thereby alleviating the progression of acute *** The study involved 90 patients diagnosed with acute pancreatitis,admitted to our hospital between March 2020 and November 2022.A retrospective analysis was conducted,categorizing patients based on Ranson score severity into mild(n=25),moderate(n=30),and severe(n=35)*** data was collected for each *** blot analysis assessed PLD2 protein expression in patient ***-time reverse transcription polymerase chain reaction was used to evaluate the mRNA expression of chemokine receptors associated with neutrophil *** levels of inflammatory factors in patients were detected using enzyme-linked immunosorbent *** migration tests were conducted to compare migration of neutrophils across groups and analyze the influence of PLD2 on neutrophil *** Overall data analysis did not find significant differences between patient groups(P>0.05).The expression of PLD2 protein in the severe group was lower than that in the moderate and mild groups(P<0.05).The expression level of PLD2 in the moderate group was also lower than that in the mild group(P<0.05).The severity of acute pancreatitis is negatively correlated with PLD2 expression(r=-0.75,P=0.002).The mRNA levels of C-X-C chemokine receptor type 1,C-X-C chemokine receptor type 2,C-C chemokine receptor type 2,and C-C chemokine receptor type 5 in the severe group are significantly higher than those in the moderate and mild groups(P<0.05),and the expression levels in the moderate group are also higher than those in the mild group(P<0.05).The levels of C-reactive protein,tumo

关键词： Phospholipase D2 Neutrophil migration Acute pancreatitis Retrospective analysis Inflammatory response

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Bidirectional regulation of the brain-gut-microbiota axis following traumatic brain injury

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Neural Regeneration Research 2025年第8期20卷 2153-2168页

作者： Xinyu You Lin niu Jiafeng Fu Shining Ge Jiangwei Shi Yanjun Zhang Pengwei Zhuang National Key Laboratory of Chinese Medicine Modernization Tianjin University of Traditional Chinese MedicineTianjinChina Haihe Laboratory of Modern Chinese Medicine Tianjin University of Traditional Chinese MedicineTianjinChina First Teaching Hospital of Tianjin University of Traditional Chinese Medicine TianjinChina National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion TianjinChina

Traumatic brain injury is a prevalent disorder of the central nervous *** addition to primary brain parenchymal damage,the enduring biological consequences of traumatic brain injury pose long-term risks for patients with traumatic brain injury;however,the underlying pathogenesis remains unclear,and effective intervention methods are *** dysfunction is a significant consequence of traumatic brain *** the most densely innervated peripheral tissue in the body,the gut possesses multiple pathways for the establishment of a bidirectional“brain-gut axis”with the central nervous *** gut harbors a vast microbial community,and alterations of the gut niche contribute to the progression of traumatic brain injury and its unfavorable prognosis through neuronal,hormonal,and immune pathways.A comprehensive understanding of microbiota-mediated peripheral neuroimmunomodulation mechanisms is needed to enhance treatment strategies for traumatic brain injury and its associated *** comprehensively reviewed alterations in the gut microecological environment following traumatic brain injury,with a specific focus on the complex biological processes of peripheral nerves,immunity,and microbes triggered by traumatic brain injury,encompassing autonomic dysfunction,neuroendocrine disturbances,peripheral immunosuppression,increased intestinal barrier permeability,compromised responses of sensory nerves to microorganisms,and potential effector nuclei in the central nervous system influenced by gut ***,we reviewed the mechanisms underlying secondary biological injury and the dynamic pathological responses that occur following injury to enhance our current understanding of how peripheral pathways impact the outcome of patients with traumatic brain *** review aimed to propose a conceptual model for future risk assessment of central nervous system-related diseases while elucidating novel insights into the bidirectional effec

关键词： traumatic brain injury brain-gut-microbiome axis gut microbiota neuroimmune immunosuppression host defense vagal afferents bacterial infection dorsal root ganglia nociception neural circuitry

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C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 pathway as a therapeutic target and regulatory mechanism for spinal cord injury

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Neural Regeneration Research 2025年第8期20卷 2231-2244页

作者： Xiangzi Wang Xiaofei niu Yingkai Wang Yang Liu Cheng Yang Xuyi Chen Zhongquan Qi School of Medicine Guangxi UniversityNanningGuangxi Zhuang Autonomous RegionChina Graduate School of Tianjin University of Traditional Chinese Medicine TianjinChina Characteristic Medical Center of People’s Armed Police Forces TianjinChina Fujian Maternity and Child Health Hospital FuzhouFujian ProvinceChina

Spinal cord injury involves non-reversible damage to the central nervous system that is characterized by limited regenerative capacity and secondary inflammatory *** expression of the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis exhibits significant differences before and after *** studies have revealed that the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis is closely associated with secondary inflammatory responses and the recruitment of immune cells following spinal cord injury,suggesting that this axis is a novel target and regulatory control point for *** review comprehensively examines the therapeutic strategies targeting the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis,along with the regenerative and repair mechanisms linking the axis to spinal cord ***,we summarize the upstream and downstream inflammatory signaling pathways associated with spinal cord injury and the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 *** review primarily elaborates on therapeutic strategies that target the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the latest progress of research on antagonistic drugs,along with the approaches used to exploit new therapeutic targets within the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the development of targeted ***,there are presently no clinical studies relating to spinal cord injury that are focusing on the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 *** review aims to provide new ideas and therapeutic strategies for the future treatment of spinal cord injury.

关键词： apoptosis C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 pathway C-C motif chemokine receptor 2 antagonists chemokine ligand 2 chemokine receptor 2 inflammation macrophage microglia spinal cord injury therapeutic method

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