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Pharmacological interventions targeting the microcirculation following traumatic spinal cord injury

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Neural Regeneration research 2024年第1期19卷 35-42页

作者： Rongrong Wang Jinzhu Bai department of Spine and spinal Cord surgery Beijing Bo’ai HospitalChina Rehabilitation Research CenterBeijingChina School of Rehabilitation Medicine Capital Medical UniversityBeijingChina

Traumatic spinal cord injury is a devastating disorder chara cterized by sensory,motor,and autonomic dysfunction that seve rely compromises an individual's ability to perform activities of daily living.These adve rse outcomes are closely related to the complex mechanism of spinal cord injury,the limited regenerative capacity of central neurons,and the inhibitory environment fo rmed by traumatic injury.Disruption to the microcirculation is an important pathophysiological mechanism of spinal cord injury.A number of therapeutic agents have been shown to improve the injury environment,mitigate secondary damage,and/or promote regeneration and repair.Among them,the spinal cord microcirculation has become an important target for the treatment of spinal cord injury.Drug inte rventions targeting the microcirculation can improve the microenvironment and promote recovery following spinal cord injury.These drugs target the structure and function of the spinal cord microcirculation and are essential for maintaining the normal function of spinal neuro ns,axons,and glial cells.This review discusses the pathophysiological role of spinal cord microcirculation in spinal cord injury,including its structure and histopathological changes.Further,it summarizes the progress of drug therapies targeting the spinal cord mic rocirc ulation after spinal cord injury.

关键词： blood-spinal cord barrier drug therapy microcirculation microvascular blood flow neuroprotection pharmacological intervention pharmacotherapy spinal cord injury trauma

Harnessing cytokine-induced killer cells to accelerate diabetic wound healing: an approach to regulating post-traumatic inflammation

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Regenerative Biomaterials 2024年第2期3卷 88-99页

作者： Yixi Yang Cheng Zhang Yuan Jiang Yijun He iawei Cai Lin Liang Zhaohuan Chen Sicheng Pan Chu Hua Keke Wu Le Wang Zhiyong Zhang Translational research Centre of Regenerative Medicine and 3D Printing of Guangzhou Medical University Guangdong Province Engineering Research Center for Biomedical EngineeringState Key Laboratory of Respiratory DiseaseDepartment of Orthopaedic SurgeryMedical Technology and Related Equipment Research for Spinal Injury TreatmentCity Key LaboratoryThe Third Affliated Hospital of Guangzhou Medical UniversitySchool of Biomedical EngineeringGuangzhou MedicalUniversityGuangzhouGuangdong510150P.R.China department of Osteoarthropathy and Sports Medicine Panyu Central HospitalGuangzhou 511400P.R.China

Impaired immunohomeostasis in diabetic wounds prolongs infiammation and cytokine dysfunction,thus,delaying or pre-venting wound-surface healing.Extensive clinical studies have been conducted on cytokine-induced killer(CIK)cells recently,as they can be easily proliferated using a straightforward,inex-pensive protocol.Therefore,the function of CIK cells in regulat-ing inflammatory environments has been drawing attention for clinical management.Throughout the current investigation,we discovered the regenerative capacity of these cells in the chal-lenging environment of wounds that heal poorly due to diabe-tes.We demonstrated that the intravenous injection of CIK cells can re-establish a proregenerative inflammatory microenviron-ment.promote larizationand.ultimatel accelerateskin healing in diabetic mice.The results indicated that CIK cell treatment affects macrophage polarization and restores the function regenerative cells under hyperglycemic conditions.This novel cellular therapy offers a promising intervention for clinical applic tions through specific inflammatory regulation functions.

关键词： macrophage diabetic wound post-traumatic inflammation cytokine-induced killer cells vascularization

Surgical intervention combined with weight-bearing walking training promotes recovery in patients with chronic spinal cord injury:a randomized controlled study

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Neural Regeneration research 2024年第12期19卷 2773-2784页

作者： Hui Zhu James D.Guest Sarah Dunlop Jia-Xin Xie Sujuan Gao Zhuojing Luo Joe E.Springer Wutian Wu Wise Young Wai Sang Poon Song Liu Hongkun Gao Tao Yu Dianchun Wang Libing Zhou Shengping Wu Lei Zhong Fang Niu Xiaomei Wang Yansheng Liu Kwok-Fai So Xiao-Ming Xu Kunming Tongren Hospital KunmingYunnan ProvinceChina Neurological surgery and the Miami Project to Cure ParalysisMiller School of MedicineUniversity of MiamiMiamiFLUSA School of Biological Sciences The University of Western AustraliaPerthWAAustralia Minderoo Foundation PerthWAAustralia Clinical Center for spinal Cord Injury Kunming General Hospital of Chengdu Military CommandKunmingYunnan ProvinceChina department of Biostatistics and Health Data Science Indiana University School of MedicineIndianapolisINUSA department of Orthopedic spinal surgery Xijing HospitalFourth Military Medical UniversityXi’anShaanxi ProvinceChina spinal Cord and Brain Injury research Center Department of Physical Medicine and RehabilitationUniversity of Kentucky College of MedicineLexingtonKYUSA Guangdong-HongKong-Macao institute of CNS Regeneration Jinan UniversityGuangzhouGuangdong ProvinceChina W.M.Keck Center for Collaborative Neuroscience Rutgers UniversityPiscatawayNJUSA Neurosurgery department Chinese University of Hong KongPrince of Wales HospitalHong Kong Special Administration RegionChina spinal Cord and Brain Injury research Group Stark Neurosciences Research InstituteDepartment of Neurological SurgeryIndiana University School of MedicineIndianapolisINUSA

For patients with chronic spinal cord injury,the co nventional treatment is rehabilitation and treatment of spinal cord injury complications such as urinary tract infection,pressure sores,osteoporosis,and deep vein thrombosis.surgery is rarely perfo rmed on spinal co rd injury in the chronic phase,and few treatments have been proven effective in chronic spinal cord injury patients.Development of effective therapies fo r chronic spinal co rd injury patients is needed.We conducted a randomized controlled clinical trial in patients with chronic complete thoracic spinal co rd injury to compare intensive rehabilitation(weight-bearing walking training)alone with surgical intervention plus intensive rehabilitation.This clinical trial was registered at ClinicalTrials.gov(NCT02663310).The goal of surgical intervention was spinal cord detethering,restoration of cerebrospinal fluid flow,and elimination of residual spinal cord compression.We found that surgical intervention plus weight-bearing walking training was associated with a higher incidence of American spinal Injury Association Impairment Scale improvement,reduced spasticity,and more rapid bowel and bladder functional recovery than weight-bearing walking training alone.Overall,the surgical procedures and intensive rehabilitation were safe.American spinal Injury Association Impairment Scale improvement was more common in T7-T11 injuries than in T2-T6 injuries.surgery combined with rehabilitation appears to have a role in treatment of chronic spinal cord injury patients.

关键词： chronic spinal cord injury intensive rehabilitation locomotor training neurological recovery surgical intervention weightbearing walking training

Subarachnoid hemorrhage misdiagnosed as acute coronary syndrome leading to catastrophic neurologic injury: A case report

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World Journal of Clinical Cases 2024年第1期12卷 148-156页

作者： Jun-Ming Lin Xiao-Jun Yuan Guang Li Xin-Rong Gan Wen-Hua Xu department of orthopaedic surgery People's Hospital of Yichun CityYichun 336000Jiangxi ProvinceChina

BACKGROUND Elevated levels of cardiac troponin and abnormal electrocardiogram changes are the primary basis for clinical diagnosis of acute coronary syndrome(ACS).Troponin levels in ACS patients can often be more than 50 times the upper reference limit.Some patients with subarachnoid hemorrhage(SAH)also show electrocardiogram abnormalities,myocardial damage,and elevated cardiac biomarkers.Unlike ACS patients,patients with SAH only have a slight increase in troponin,and the use of anticoagulants or antiplatelet drugs is prohibited.Because of the opposite treatment modalities,it is essential for clinicians to distinguish between SAH and ACS.CASE SUMMARY A 56-year-old female patient was admitted to the emergency department at night with a sudden onset of severe back pain.The final diagnosis was intraspinal hematoma in the thoracic spine.We performed an emergency thoracic spinal canal hematoma evacuation procedure with the assistance of a microscope.Intraoperatively,diffuse hematoma formation was found in the T7-T10 spinal canal,and no obvious spinal vascular malformation changes were observed.Postoperative head and spinal magnetic resonance imaging(MRI)showed a small amount of SAH in the skull,no obvious abnormalities in the cervical and thoracic spinal canals,and no abnormal signals in the lumbar spinal canal.Thoracoab-dominal aorta computed tomography angiography showed no vascular malfor-mation.Postoperative motor system examination showed Medical research Council Scale grade 1/5 strength in both lower extremities,and the patient experienced decreased sensation below the T12 rib margin and reported a Visual Analog Scale score of 3.CONCLUSION Extremely elevated troponin levels(more than 50 times the normal range)are not unique to coronary artery disease.SAH can also result in extremely high troponin levels,and antiplatelet drugs are contraindicated in such cases.Emergency MRI can help in the early differential diagnosis,as a misdiagnosis of ACS can lead to catastrophic neurological damage in patients with spontane

关键词： Acute coronary syndrome Spontaneous spinal subdural hematoma Misdiagnosis Catastrophic neurological injury Case report

Enhancement of motor functional recovery in thoracic spinal cord injury: voluntary wheel running versus forced treadmill exercise

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Neural Regeneration research 2025年第3期20卷 836-844页

作者： Do-Hun Lee Dan Cao Younghye Moon Chen Chen Nai-Kui Liu Xiao-Ming Xu Wei Wu spinal Cord and Brain Injury research Group Stark Neurosciences Research InstituteIndiana University School of MedicineIndianapolisINUSA department of Neurological surgery Indiana University School of MedicineIndianapolisINUSA department of Neuroscience Baylor College of MedicineHoustonTXUSA

spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery and morphological changes following thoracic contusive spinal cord injury. After a 7-day recovery period after spinal cord injury, mice were assigned to either a trained group(10 weeks of voluntary running wheel or forced treadmill exercise) or an untrained group. Bi-weekly assessments revealed that the exercise-trained group, particularly the voluntary wheel exercise subgroup, displayed significantly improved locomotor recovery, more plasticity of dopaminergic and serotonin modulation compared with the untrained group. Additionally, exercise interventions led to gait pattern restoration and enhanced transcranial magnetic motor-evoked potentials. Despite consistent injury areas across groups, exercise training promoted terminal innervation of descending axons. In summary, voluntary wheel exercise shows promise for enhancing outcomes after thoracic contusive spinal cord injury, emphasizing the role of exercise modality in promoting recovery and morphological changes in spinal cord injuries. Our findings will influence future strategies for rehabilitation exercises, restoring functional movement after spinal cord injury.

关键词： behavioral assessment motor function neural plasticity running wheel exercise spinal cord injury treadmill exercise voluntary exercise

Human umbilical cord mesenchymal stem cell-derived exosomes loaded into a composite conduit promote functional recovery after peripheral nerve injury in rats

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Neural Regeneration research 2024年第4期19卷 900-907页

作者： Haoshuai Tang Junjin Li Hongda Wang Jie Ren Han Ding Jun Shang Min Wang Zhijian Wei Shiqing Feng department of Othopaedics Tianjin Medical University General Hospital International Science and Technology Cooperation Base of spinal Cord Injury Tianjin Key Laboratory of Spine and Spinal Cord InjuryDepartment of OrthopedicsTianjin Medical University General Hospital Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment Tianjin Lung Cancer InstituteTianjin Medical University General Hospital department of Othopaedics Qilu Hospital of Shandong UniversityShandong University Centre for OthopedicsAdvanced Medical Research InstituteShandong University Orthopedic research Center of Shandong University&Advanced Medical research institute Cheeloo College of MedicineShandong University

Complete transverse injury of peripheral nerves is challenging to treat.Exosomes secreted by human umbilical cord mesenchymal stem cells are considered to play an important role in intercellular communication and regulate tissue regeneration.In previous studies,a collagen/hyaluronic acid sponge was shown to provide a suitable regeneration environment for Schwann cell proliferation and to promote axonal regeneration.This three-dimensional(3D)composite conduit contains a collagen/hyaluronic acid inner sponge enclosed in an electrospun hollow poly(lactic-co-glycolic acid)tube.However,whether there is a synergy between the 3D composite conduit and exosomes in the repair of peripheral nerve injury remains unknown.In this study,we tested a comprehensive strategy for repairing long-gap(10 mm)peripheral nerve injury that combined the 3D composite conduit with human umbilical cord mesenchymal stem cell-derived exosomes.Repair effectiveness was evaluated by sciatic functional index,sciatic nerve compound muscle action potential recording,recovery of muscle mass,measuring the cross-sectional area of the muscle fiber,Masson trichrome staining,and transmission electron microscopy of the regenerated nerve in rats.The results showed that transplantation of the 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes promoted peripheral nerve regeneration and restoration of motor function,similar to autograft transplantation.More CD31-positive endothelial cells were observed in the regenerated nerve after transplantation of the loaded conduit than after transplantation of the conduit without exosomes,which may have contributed to the observed increase in axon regeneration and distal nerve reconnection.Therefore,the use of a 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes represents a promising cell-free therapeutic option for the treatment of peripheral nerve injury.

关键词： axon growth collagen exosome human umbilical cord mesenchymal stem cells hyaluronic acid muscular atrophy nerve guidance conduits peripheral nerve regeneration

Engineered stem cells by emerging biomedical stratagems

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Science Bulletin 2024年第2期69卷 248-279页

作者： Jinglin Wang Xiaoxuan Zhang Hanxu Chen Haozhen Ren Min Zhou Yuanjin Zhao department of Vascular surgery.Nanjing Drum Tower Hospital Affliated Hospital of Medical SchoolNanjing UniversityNanjing 210008China Division of Hepatobiliary surgery and Transplantation surgery Department of General SurgeryNanjing Drum Tower HospitalSchool of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China Shenzhen research institute Southeast UniversityShenzhen 518038China

Stem cell therapy holds immense potential as a viable treatment for a widespread range of intractable disorders.As the safety of stem cell transplantation having been demonstrated in numerous clinical trials,various kinds of stem cells are currently utilized in medical applications.Despite the achievements,the therapeutic benefits of stem cells for diseases are limited,and the data of clinical researches are unstable.To optimize tthe effectiveness of stem cells,engineering approaches have been developed to enhance their inherent abilities and impart them with new functionalities,paving the way for the next generation of stem cell therapies.This review offers a detailed analysis of engineered stem cells,including their clinical applications and potential for future development.We begin by briefly introducing the recent advances in the production of stem cells(induced pluripotent stem cells(ipsCs),embryonic stem cells(ESCs),mesenchymal stem cells(MSCs)and hematopoietic stem cells(HSCs).Furthermore,we present the latest developments of engineered strategies in stem cells,including engineered methods in molecular biology and biomaterial fields,and their application in biomedical research.Finally,we summarize the current obstacles and suggest future prospects for engineered stem cells in clinical translations and biomedical applications.

关键词： Stem cells Genetic modification Biomaterials Microfluidics Organ-on-a-chip Bioprinting

Garg incontinence scores: New scoring system on the horizon to evaluate fecal incontinence. Will it make a difference?

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World Journal of Gastroenterology 2024年第3期30卷 204-210页

作者： Petr Tsarkov Inna Tulina Parvez Sheikh Darya D Shlyk Pankaj Garg department of Colorectal surgery Sechenov First Moscow State Medical UniversityMoscow 119991Russia department of Oncologic Colorectal surgery Sechenov First Moscow State Medical UniversityMoscow 119991Russia department of Colorectal surgery Saifee HospitalMumbai 400004MaharashtraIndia department of Colorectal surgery Garg Fistula Research InstitutePanchkula 134113HaryanaIndia

The main aim of this opinion review is to comment on the recent article published by Garg et al in the World Journal of Gastroenterology 2023;29:4593–4603.The authors in the published article developed a new scoring system,Garg incon-tinence scores(GIS),for fecal incontinence(FI).FI is a chronic debilitating disease that has a severe negative impact on the quality of life of the patients.Rome IV criteria define FI as multiple episodes of solid or liquid stool passed into the clothes at least twice a month.The associated social stigmatization often leads to significant under-reporting of the condition,which further impairs management.An important point is that the complexity and vagueness of the disease make it difficult for the patients to properly define and report the magnitude of the problem to their physicians.Due to this,the management becomes even more difficult.This issue is resolved up to a considerable extent by a scoring ques-tionnaire.There were several scoring systems in use for the last three decades.The prominent of them were the Cleveland Clinic scoring system or the Wexner scoring system,St.Marks Hospital or Vaizey’s scores,and the FI severity index.However,there were several shortcomings in these scoring systems.In the opinion review,we tried to analyze the strength of GIS and compare it to the existing scoring systems.The main pitfalls in the existing scoring systems were that most of them gave equal weightage to different types of FI(solid,liquid,flatus,etc.),were not comprehensive,and took only the surgeon’s perception of FI into view.In GIS,almost all shortcomings of previous scoring systems had been addressed:different weights were assigned to different types of FI by a robust statistical methodology;the scoring system was made comprehensive by including all types of FI that were previously omitted(urge,stress and mucus FI)and gave priority to patients’rather than the physicians’perceptions while developing the scoring system.Due to this,GIS indeed looked like a paradigm shift in the evaluat

关键词： Fecal incontinence Scoring system Urge Stress Flatus

Epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China:a hospital-based retrospective study

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Neural Regeneration research 2024年第5期19卷 1126-1132页

作者： Hengxing Zhou Yongfu Lou Lingxiao Chen Yi Kang Lu Liu Zhiwei Cai David BAnderson Wei Wang Chi Zhang Jinghua Wang Guangzhi Ning Yanzheng Gao Baorong He Wenyuan Ding Yisheng Wang Wei Mei Yueming Song Yue Zhou Maosheng Xia Huan Wang Jie Zhao Guoyong Yin Tao Zhang Feng Jing Rusen Zhu Bin Meng Li Duan Zhongmin Zhang Desheng Wu Zhengdong Cai Lin Huang Zhanhai Yin Kainan Li Shibao Lu Shiqing Feng department of Orthopedics The Second HospitalCheeloo College of MedicineShandong UniversityShandongChina department of Orthopedics Shandong University Center for OrthopedicsQilu HospitalCheeloo College of MedicineShandong UniversityShandongChina department of Orthopedics Tianjin Medical University General HospitalInternational Science and Technology Cooperation Base of Spinal Cord InjuryTianjin Key Laboratory of Spine and Spinal CordTianjinChina Faculty of Medicine and Health The Back Pain Research TeamSydney Musculoskeletal HealthThe Kolling InstituteUniversity of SydneySydneyNSWAustralia department of Spine surgery Honghui HospitalXi’an Jiaotong UniversityXi’anShaanxi ProvinceChina department of Burns and Plastic surgery The Fourth Medical Center of Chinese PLA General HospitalBeijingChina Faculty of Medicine and Health School of Health SciencesUniversity of SydneyNSWAustralia Sydney Spine institute BurwoodSydneyNSWAustralia Laboratory of Epidemiology Tianjin Neurological InstituteDepartment of NeurologyTianjin Medical University General Hospital&Tianjin Neurological InstituteKey Laboratory of Post-Neuroinjury Neuro-repair and Regeneration in Central Nervous SystemMinistry of Education and Tianjin CityTianjinChina department of Orthopedics Henan Provincial People’s HospitalZhengzhouHenan ProvinceChina department of spinal surgery The Third Hospital of Hebei Medical UniversityShijiazhuangHebei ProvinceChina department of Orthopedics The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina department of Spine surgery Zhengzhou Orthopedics HospitalZhengzhouHenan ProvinceChina department of Orthopedic surgery and Orthopedic research institute West China HospitalSichuan UniversityChengduSichuan ProvinceChina department of Orthopedics Xinqiao HospitalArmy Medical UniversityChongqingChina department of Orthopedics The First Affiliated Hospital of China Medical UniversityShenyangLiaoning ProvinceChina department of spinal surgery Shengj

Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death.China has the largest population of patients with traumatic spinal cord injury.Previous studies of traumatic spinal cord injury in China have mostly been regional in scope;national-level studies have been rare.To the best of our knowledge,no national-level study of treatment status and economic burden has been performed.This retrospective study aimed to examine the epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China at the national level.We included 13,465 traumatic spinal cord injury patients who were injured between January 2013 and December 2018 and treated in 30 hospitals in 11 provinces/municipalities representing all geographical divisions of China.Patient epidemiological and clinical features,treatment status,and total and daily costs were recorded.Trends in the percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department and cost of care were assessed by annual percentage change using the Joinpoint Regression Program.The percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department did not significantly change overall(annual percentage change,-0.5%and 2.1%,respectively).A total of 10,053(74.7%)patients underwent surgery.Only 2.8%of patients who underwent surgery did so within 24 hours of injury.A total of 2005(14.9%)patients were treated with high-dose(≥500 mg)methylprednisolone sodium succinate/methylprednisolone(MPSS/MP);615(4.6%)received it within 8 hours.The total cost for acute traumatic spinal cord injury decreased over the study period(-4.7%),while daily cost did not significantly change(1.0%increase).Our findings indicate that public health initiatives should aim at improving hospitals’ability to complete early surgery within 24 hours,which is associated with improved sensorimot

关键词： China clinical features costs epidemiology methylprednisolone sodium succinate methylprednisolone retrospective study traumatic spinal cord injury treatment