Publications by authors named "Zikuan Leng"

8 Publications

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Transplantation of ACE2 Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia.

Aging Dis 2020 Apr 9;11(2):216-228. Epub 2020 Mar 9.

9The Executive Committee on Anti-aging and Disease Prevention in the framework of Science and Technology, Pharmacology and Medicine Themes under an Interactive Atlas along the Silk Roads, UNESCO, Paris, France.

A coronavirus (HCoV-19) has caused the novel coronavirus disease (COVID-19) outbreak in Wuhan, China. Preventing and reversing the cytokine storm may be the key to save the patients with severe COVID-19 pneumonia. Mesenchymal stem cells (MSCs) have been shown to possess a comprehensive powerful immunomodulatory function. This study aims to investigate whether MSC transplantation improves the outcome of 7 enrolled patients with COVID-19 pneumonia in Beijing YouAn Hospital, China, from Jan 23, 2020 to Feb 16, 2020. The clinical outcomes, as well as changes of inflammatory and immune function levels and adverse effects of 7 enrolled patients were assessed for 14 days after MSC injection. MSCs could cure or significantly improve the functional outcomes of seven patients without observed adverse effects. The pulmonary function and symptoms of these seven patients were significantly improved in 2 days after MSC transplantation. Among them, two common and one severe patient were recovered and discharged in 10 days after treatment. After treatment, the peripheral lymphocytes were increased, the C-reactive protein decreased, and the overactivated cytokine-secreting immune cells CXCR3+CD4+ T cells, CXCR3+CD8+ T cells, and CXCR3+ NK cells disappeared in 3-6 days. In addition, a group of CD14+CD11c+CD11b regulatory DC cell population dramatically increased. Meanwhile, the level of TNF-α was significantly decreased, while IL-10 increased in MSC treatment group compared to the placebo control group. Furthermore, the gene expression profile showed MSCs were ACE2 and TMPRSS2 which indicated MSCs are free from COVID-19 infection. Thus, the intravenous transplantation of MSCs was safe and effective for treatment in patients with COVID-19 pneumonia, especially for the patients in critically severe condition.
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http://dx.doi.org/10.14336/AD.2020.0228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069465PMC
April 2020

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

A survey of 434 clinical trials about coronavirus disease 2019 in China.

J Med Virol 2020 10 27;92(10):1715-1717. Epub 2020 Mar 27.

Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

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http://dx.doi.org/10.1002/jmv.25779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228410PMC
October 2020

Interface Fixation Using Absorbable Screws versus Plate Fixation in Anterior Cervical Corpectomy and Fusion for Two-Level Cervical Spondylotic Myelopathy.

Med Sci Monit 2020 Mar 20;26:e921507. Epub 2020 Mar 20.

Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henen, China (mainland).

BACKGROUND We compared the clinical and radiographic outcomes between interface fixation using absorbable screws and plate fixation in anterior cervical corpectomy and fusion (ACCF) to evaluate the effectiveness of these 2 fixation methods for the treatment of 2-level cervical spondylotic myelopathy (CSM). MATERIAL AND METHODS From January 2014 to December 2016, a total of 220 patients who received 2-level ACCF were retrospectively collected. Among them, 108 patients were treated with interface fixation using absorbable screws (Group A) and 112 patients underwent plate fixation (Group B). Japanese Orthopedic Association (JOA) score and Neck Disability Index (NDI) score were employed to compare the clinical improvement. Operative time, blood loss, surgical cost, cervical lordosis, complications, and fusion rate were also evaluated. RESULTS The average follow-up time were 35.2±4.5 months in Group A and 35.9±3.9 months in Group B. There was no difference in operative time and blood loss for both groups. The JOA scores and NDI scores were similar in each follow-up (p>0.05 in all). Group A cost an average of 30% less than Group B for the operation. Both groups achieved 100% in the fusion rate with the same conditions in cervical lordosis. Group A (5/108) had a significantly lower complication rate than Group B (17/112) (p<0.05). CONCLUSIONS ACCF with interface fixation using absorbable screws achieved similar clinical outcomes compared to ACCF with plate fixation for 2-level CSM. Moreover, the interface fixation using absorbable screws presented far fewer complications and cost less for the operation.
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http://dx.doi.org/10.12659/MSM.921507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106970PMC
March 2020

Quantitative Analysis of SSEA3+ Cells from Human Umbilical Cord after Magnetic Sorting.

Cell Transplant 2019 07 18;28(7):907-923. Epub 2019 Apr 18.

2 W.M. Keck Center for Collaborative Neuroscience, Rutgers, the State University of New Jersey, Piscataway, New Jersey, USA.

Multilineage-differentiating stress-enduring (Muse) cells are a population of pluripotent stage-specific embryonic antigen 3 (SSEA3)+ mesenchymal stem cells first described by Mari Dezawa in 2010. Although some investigators have reported SSEA3+ mesenchymal cells in umbilical cord tissues, none have quantitatively compared SSEA3+ cells isolated from Wharton's jelly (WJ) and the cord lining (CL) of human umbilical cords (HUCs). We separated WJ and the CL from HUCs, cultured mesenchymal stromal cells (MSCs) isolated from these two tissues with collagenase, and quantified the percentage of SSEA3+ cells over three passages. The first passage had 5.0% ± 4.3% and 5.3% ± 5.1% SSEA3+ cells from WJ and the CL, respectively, but the percentage of SSEA3+ cells decreased significantly ( < 0.05) between P0 and P2 in the CL group and between P0 and P1 in the WJ group. Magnetic-activated cell sorting (MACS) markedly enriched SSEA3+ cells to 91.4% ± 3.2%. Upon culture of the sorted population, we found that the SSEA3+ percentage ranged from 62.5% to 76.0% in P2-P5 and then declined to 42.0%-54.7% between P6 and P9. At P10, the cultures contained 37.4% SSEA3+ cells. After P10, we resorted the cells and achieved 89.4% SSEA3+ cells in culture. The procedure for MACS-based enrichment of SSEA3+ cells, followed by expansion in culture and a re-enrichment step, allows the isolation of many millions of SSEA3+ cells in relatively pure culture. When cultured, the sorted SSEA3+ cells differentiated into embryoid spheres and survived 4 weeks after transplant into a contused Sprague-Dawley rat spinal cord. The transplanted SSEA3+ cells migrated into the injury area from four injection points around the contusion site and did not produce any tumors. The umbilical cord is an excellent source of fetal Muse cells, and our method allows the practical and efficient isolation and expansion of relatively pure populations of SSEA3+ Muse cells that can be matched by human leukocyte antigen for transplantation in human trials.
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http://dx.doi.org/10.1177/0963689719844260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6719495PMC
July 2019

Olfactory ensheathing cell transplantation for spinal cord injury: An 18-year bibliometric analysis based on the Web of Science.

Neural Regen Res 2013 May;8(14):1286-96

Department of Orthopedics, the Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.

Objective: Olfactory ensheathing cell (OEC) transplantation is a promising new approach for the treatment of spinal cord injury (SCI), and an increasing number of scientific publications are devoted to this treatment strategy. This bibliometric analysis was conducted to assess global research trends in OEC transplantation for SCI.

Data Source: All of the data in this study originate from the Web of Science maintained by the Institute for Scientific Information, USA, and includes SCI-EXPANDED, SSCI, A&HCI, CPCI-S, CPCI-SSH, BKCI-S, BKCI-SSH, CCR-EXPANDED and IC. The Institute for Scientific Information's Web of Science was searched using the keywords "olfactory ensheathing cells" or "OECs" or "olfactory ensheathing glia" or "OEG" or "olfactory ensheathing glial cells" or "OEGs" and "spinal cord injury" or "SCI" or "spinal injury" or "spinal transection" for literature published from January 1898 to May 2012.

Data Selection: Original articles, reviews, proceedings papers and meeting abstracts, book chapters and editorial materials on OEC transplantation for SCI were included. Simultaneously, unpublished literature and literature for which manual information retrieval was required were excluded.

Main Outcome Measures: ALL SELECTED LITERATURES ADDRESSING OEC TRANSPLANTATION FOR SCI WERE EVALUATED IN THE FOLLOWING ASPECTS: publication year, document type, language, author, institution, times cited, Web of Science category, core source title, countries/territories and funding agency.

Results: In the Web of Science published by the Institute for Scientific Information, the earliest literature record was in April, 1995. Four hundred and fourteen publications addressing OEC transplantation for SCI were added to the data library in the past 18 years, with an annually increasing trend. Of 415 records, 405 publications were in English. Two hundred and fifty-nine articles ranked first in the distribution of document type, followed by 141 reviews. Thirty articles and 20 reviews, cited more than 55 times by the date the publication data were downloaded by us, can be regarded as the most classical references. The journal Experimental Neurology published the most literature (32 records), followed by Glia. The United States had the most literature, followed by China. In addition, Yale University was the most productive institution in the world, while The Second Military Medical University contributed the most in China. The journal Experimental Neurology published the most OEC transplantation literature in the United States, while Neural Regeneration Research published the most in China.

Conclusion: This analysis provides insight into the current state and trends in OEC transplantation for SCI research. Furthermore, we anticipate that this analysis will help encourage international cooperation and teamwork on OEC transplantation for SCI to facilitate the development of more effective treatments for SCI.
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http://dx.doi.org/10.3969/j.issn.1673-5374.2013.14.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4107648PMC
May 2013

A supplementary study from China: the use of pain medications after operative treatment of an ankle fracture.

Injury 2013 Nov 20;44(11):1656-7. Epub 2013 Feb 20.

Department of Orthopedics, Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an 710004, China.

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http://dx.doi.org/10.1016/j.injury.2013.01.037DOI Listing
November 2013