Publications by authors named "Pengrong Ouyang"

6 Publications

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Dorsal raphe serotonergic neurons promote arousal from isoflurane anesthesia.

CNS Neurosci Ther 2021 May 11. Epub 2021 May 11.

Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

Aims: General anesthesia has been widely applied in surgical or nonsurgical medical procedures, but the mechanism behind remains elusive. Because of shared neural circuits of sleep and anesthesia, whether serotonergic system, which is highly implicated in modulation of sleep and wakefulness, regulates general anesthesia as well is worth investigating.

Methods: Immunostaining and fiber photometry were used to assess the neuronal activities. Electroencephalography spectra and burst-suppression ratio (BSR) were used to measure anesthetic depth and loss or recovery of righting reflex to indicate the induction or emergence time of general anesthesia. Regulation of serotonergic system was achieved through optogenetic, chemogenetic, or pharmacological methods.

Results: We found that both Fos expression and calcium activity were significantly decreased during general anesthesia. Activation of 5-HT neurons in the dorsal raphe nucleus (DRN) decreased the depth of anesthesia and facilitated the emergence from anesthesia, and inhibition deepened the anesthesia and prolonged the emergence time. Furthermore, agonism or antagonism of 5-HT 1A or 2C receptors mimicked the effect of manipulating DRN serotonergic neurons.

Conclusion: Our results demonstrate that 5-HT neurons in the DRN play a regulative role of general anesthesia, and activation of serotonergic neurons could facilitate emergence from general anesthesia partly through 5-HT 1A and 2C receptors.
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http://dx.doi.org/10.1111/cns.13656DOI Listing
May 2021

Exosomes from microRNA-126 overexpressing mesenchymal stem cells promote angiogenesis by targeting the PIK3R2-mediated PI3K/Akt signalling pathway.

J Cell Mol Med 2021 Feb 21;25(4):2148-2162. Epub 2020 Dec 21.

Department of Orthopaedic Surgery, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.

microRNA-126 (miR-126), an endothelial-specific miRNA, is associated with vascular homeostasis and angiogenesis. However, the efficiency of miR-126-based treatment is partially compromised due to the low efficiency of miRNA delivery in vivo. Lately, exosomes have emerged as a natural tool for therapeutic molecule delivery. Herein, we investigated whether exosomes derived from bone marrow mesenchymal stem cells (BMMSCs) can be utilized to deliver miR-126 to promote angiogenesis. Exosomes were isolated from BMMSCs overexpressed with miR-126 (Exo-miR-126) by ultracentrifugation. In vitro study, Exo-miR-126 treatment promoted the proliferation, migration and angiogenesis of human umbilical vein endothelial cells (HUVECs). Furthermore, the gene/protein expression of angiogenesis-related vascular endothelial growth factor (VEGF) and angiotensin-1 (Ang-1) were up-regulated after incubation with Exo-miR-126. Additionally, the expression level of phosphoinositol-3 kinase regulatory subunit 2 (PIK3R2) showed an inverse correlation with miR-126 in HUVECs. Particularly, the Exo-miR-126 treatment contributed to enhanced angiogenesis of HUVECs by targeting PIK3R2 to activate the PI3K/Akt signalling pathway. Similarly, Exo-miR-126 administration profoundly increased the number of newly formed capillaries in wound sites and accelerated the wound healing in vivo. The results demonstrate that exosomes derived from BMMSCs combined with miR-126 may be a promising strategy to promote angiogenesis.
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http://dx.doi.org/10.1111/jcmm.16192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882955PMC
February 2021

Transplantation of sh-miR-199a-5p-Modified Olfactory Ensheathing Cells Promotes the Functional Recovery in Rats with Contusive Spinal Cord Injury.

Cell Transplant 2020 Jan-Dec;29:963689720916173

Department of Orthopaedics, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.

MicroRNAs (miRNAs) function as gene expression switches, and participate in diverse pathophysiological processes of spinal cord injury (SCI). Olfactory ensheathing cells (OECs) can alleviate pathological injury and facilitate functional recovery after SCI. However, the mechanisms by which OECs restore function are not well understood. This study aims to determine whether silencing miR-199a-5p would enhance the beneficial effects of the OECs. In this study, we measured miR-199a-5p levels in rat spinal cords with and without injury, with and without OEC transplants. Then, we transfected OECs with the sh-miR-199a-5p lentiviral vector to reduce miR-199a-5p expression and determined the effects of these OECs in SCI rats by Basso-Beattie-Bresnahan (BBB) locomotor scores, diffusion tensor imaging (DTI), and histological methods. We used western blotting to measure protein levels of Slit1, Robo2, and srGAP2. Finally, we used the dual-luciferase reporter assay to assess the relationship between miR-199-5p and Slit1, Robo2, and srGAP2 expression. We found that SCI significantly increased miR-199a-5p levels ( < 0.05), and OEC transplants significantly reduced miR-199a-5p expression ( < 0.05). Knockdown of miR-199a-5p in OECs had a better therapeutic effect on SCI rats, indicated by higher BBB scores and fractional anisotropy values on DTI, as well as histological findings. Reducing miR-199a-5p levels in transplanted OECs markedly increased spinal cord protein levels of Slit1, Robo2, and srGAP2. Our results demonstrated that transplantation of sh-miR-199a-5p-modified OECs promoted functional recovery in SCI rats, suggesting that miR-199a-5p knockdown was more beneficial to the therapeutic effects of OEC transplants. These findings provided new insights into miRNAs-mediated therapeutic mechanisms of OECs, which helps us to develop therapeutic strategies based on miRNAs and optimize cell therapy for SCI.
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http://dx.doi.org/10.1177/0963689720916173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586279PMC
June 2021

Biomechanical Comparison of 1-Level Corpectomy and 2-Level Discectomy for Cervical Spondylotic Myelopathy: A Finite Element Analysis.

Med Sci Monit 2020 Feb 5;26:e919270. Epub 2020 Feb 5.

State Key Laboratory for Manufacturing Systems Engineering, School of Mechanical Engineering, Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland).

BACKGROUND Anterior cervical discectomy and fusion (ACDF) and anterior cervical corpectomy and fusion (ACCF) are effective treatments for cervical spondylotic myelopathy (CSM), but it is unclear which is better. In this study, we compared the biomechanical properties of 2-level ACDF and 1-level ACCF. MATERIAL AND METHODS An intact C3-C7 cervical spine model was developed and validated, then ACDF and ACCF simulation models were developed. We imposed 1.0 Nm moments and displacement-controlled loading on the C3 superior endplate. The range of motions (ROMs) of surgical and adjacent segments and von Mises stresses on endplates, fixation systems, bone-screw interfaces, and bone grafts were recorded. RESULTS ACDF and ACCF significantly reduced the surgical segmental ROMs to the same extent. ACCF induced much lower stress peaks in the fixation system and bone-screw interfaces and higher stress peaks on the bone graft. ACDF induced much lower stress peaks on the C4 inferior endplate and equivalent stress on the C6 superior endplate. There was no difference in the ROMs of surgical and adjacent segments and the intradiscal stress of adjacent levels between ACDF and ACCF. CONCLUSIONS Both ACDF and ACCF can provide satisfactory spinal stability. ACDF may be beneficial for subsidence resistance due to the lower stress peaks on the endplate. The ACCF may perform better in long-term stability and bone fusion owing to the lower stress peaks in the fixation system and bone-screw interfaces, and higher stress peaks in the bone graft.
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http://dx.doi.org/10.12659/MSM.919270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020763PMC
February 2020

Prognostic Factors and Treatment Options for Patients with High-Grade Chondrosarcoma.

Med Sci Monit 2019 Nov 25;25:8952-8967. Epub 2019 Nov 25.

Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland).

BACKGROUND The goal of this study was to determine the prognostic factors exclusive for high-grade chondrosarcoma and whether adjuvant radiotherapy could achieve better overall survival (OS) or cancer-specific survival (CSS) for patients with high-grade chondrosarcoma. MATERIAL AND METHODS Surveillance, Epidemiology, and End Results (SEER) cancer registry database was utilized to extract the chondrosarcoma cases diagnosed between 1973 and 2014. Among these cases, the histological grades of poorly differentiated (grade 3) and undifferentiated (grade 4) were categorized as high-grade and included in this study. Chondrosarcoma OS and CSS were the primary outcomes in the present study. The log-rank test was performed for univariate analysis, and the Cox regression model was conducted for multivariate analysis. RESULTS A total of 743 patients with high-grade chondrosarcoma were identified in this study (430 cases were poorly differentiated tumors, and 313 cases were undifferentiated tumors). Age at diagnosis, pathological grade, histo-type, SEER stage, tumor size and surgical resection were identified as independent predictors in both OS and CSS analysis of high-grade chondrosarcoma. When stratified by histological grade, surgical resection remained the effective treatment. Strikingly, radiotherapy was determined as an independent protective factor in both OS and CSS analysis of undifferentiated (grade 4) dedifferentiated chondrosarcoma, and adjuvant radiotherapy combined surgical resection could improve both the OS and CSS of patients with undifferentiated myxoid and dedifferentiated chondrosarcoma compared with other treatment regimens. CONCLUSIONS Our study first demonstrated that adjuvant radiotherapy combined surgery could improve the survival of patients with undifferentiated myxoid and dedifferentiated chondrosarcoma. These results encourage the application of adjuvant radiotherapy for patients with high-grade chondrosarcoma and maximize the patients' outcome.
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http://dx.doi.org/10.12659/MSM.917959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6894367PMC
November 2019

Biomechanical Comparison of Integrated Fixation Cage Versus Anterior Cervical Plate and Cage in Anterior Cervical Corpectomy and Fusion (ACCF): A Finite Element Analysis.

Med Sci Monit 2019 Feb 25;25:1489-1498. Epub 2019 Feb 25.

State Key Laboratory for Manufacturing Systems Engineering, School of Mechanical Engineering, Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland).

BACKGROUND Anterior cervical plate and cage fixation system (ACPC) used in anterior cervical corpectomy and fusion (ACCF) is reported to incur excess complications. This study aimed to introduce integrated fixation cage (IFC) into ACCF to eliminate the anterior cervical plate (ACP)-related complications. MATERIAL AND METHODS One validated intact and 3 ACCF-simulated C3-C7 cervical spine models were developed. In ACCF models, C5 was corpectomied and fixed by IFC or ACPC. For each model, 1.0 Nm moments of flexion, extension, lateral bending, and torsion were imposed on the C3 vertebra. The range of motion (ROM) of each segment and the stress distribution on screw-vertebra interface, bone graft, and cage-endplate were recorded and analyzed. RESULTS ROMs of C3-C7 were not different in any motion condition between IFC and ACPC models. The maximal von Mises stress on screw-vertebra interface of the IFC model was lower than that of the ACPC models in flexion, extension, and lateral bending, but higher in rotation. The maximal von Mises stress on bone graft of the IFC model was higher compared with the ACPC models, except in flexion. The IFC model showed a higher maximal von Mises stress on cage-endplate interface in all motion planes. CONCLUSIONS Based on finite element analysis, IFC provided identical C3-C7 construct stability as ACPC. Compared with ACPC, IFC showed better biomechanical performance on screw-vertebra interface and bone graft, but worse biomechanical performance on cage-endplate interface.
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http://dx.doi.org/10.12659/MSM.913630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400022PMC
February 2019