Application of neurotrophic and proangiogenic factors as therapy after peripheral nervous system injury

The intrinsic ability of peripheral nerves to regenerate after injury is extremely limited,especially in case of severe injury.This often leads to poor motor function and permanent disability.Existing approaches for the treatment of injured nerves do not provide appropriate conditions to support survival and growth of nerve cells.This drawback can be compensated by the use of gene therapy and cell therapy-based drugs that locally provide an increase in the key regulators of nerve growth,including neurotrophic factors and extracellular matrix proteins.Each growth factor plays its own specific angiotrophic or neurotrophic role.Currently,growth factors are widely studied as accelerators of nerve regeneration.Particularly noteworthy is synergy between various growth factors,that is essential for both angiogenesis and neurogenesis.Fibroblast growth factor 2 and vascular endothelial growth factor are widely known for their proangiogenic effects.At the same time,fibroblast growth factor 2 and vascular endothelial growth factor stimulate neural cell growth and play an important role in neurodegenerative diseases of the peripheral nervous system.Taken together,their neurotrophic and angiogenic properties have positive effect on the regeneration process.In this review we provide an in-depth overview of the role of fibroblast growth factor 2 and vascular endothelial growth factor in the regeneration of peripheral nerves,thus demonstrating their neurotherapeutic efficacy in improving neuron survival in the peripheral nervous system.

Role of the Ilizarov non-free bone plasty in the management of long bone defects and nonunion: Problems solved and unsolved

BACKGROUND Ilizarov non-free bone plasty is a method of distraction osteogenesis using the Ilizarov apparatus for external fixation which originated in Russia and was disseminated across the world. It has been used in long bone defect and nonunion management along with free vascularized grafting and induced membrane technique. However, the shortcomings and problems of these methods still remain the issues which restrict their overall use.AIM To study the recent available literature on the role of Ilizarov non-free bone plasty in long bone defect and nonunion management, its problems and the solutions to these problems in order to achieve better treatment outcomes.METHODS Three databases(Pub Med, Scopus, and Web of Science) were searched for literature sources on distraction osteogenesis, free vascularized grafting and induced membrane technique used in long bone defect and nonunion treatment within a five-year period(2015-2019). Full-text clinical articles in the English language were selected for analysis only if they contained treatment results,complications and described large patient samples(not less than ten cases for congenital, post-tumor resection cases or rare conditions, and more than 20 cases for the rest). Case reports were excluded.RESULTS Fifty full-text articles and reviews on distraction osteogenesis were chosen.Thirty-five clinical studies containing large series of patients treated with this method and problems with its outcome were analyzed. It was found that distraction osteogenesis techniques provide treatment for segmental bone defects and nonunion of the lower extremity in many clinical situations, especially in complex problems. The Ilizarov techniques treat the triad of problems simultaneously(bone loss, soft-tissue loss and infection). Management of tibial defects mostly utilizes the Ilizarov circular fixator. Monolateral fixators are preferable in the femur. The use of a ring fixator is recommended in patients with an infected tibial bone gap of more than 6 cm. High rates of successful treatment were reported by the authors that ranged from 77% to 100% and depended on the pathology and the type of Ilizarov technique used. Hybrid fixation and autogenous grafting are the most applicable solutions to avoid after-frame regenerate fracture or deformity and docking site nonunion.CONCLUSION The role of Ilizarov non-free bone plasty has not lost its significance in the treatment of segmental bone defects despite the shortcomings and treatment problems encountered.

Angiogenesis and nerve regeneration induced by local administration of plasmid pBud-coVEGF165-coFGF2 into the intact rat sciatic nerve

Vascular endothelial growth factor(VEGF) and fibroblast growth factor 2(FGF2) are well-known growth factors involved in the regeneration of various tissues and organs, including peripheral nerve system. In the present study, we elucidated the local and systemic effects of plasmid construct рBud-coVEGF165-coFGF2 injected into the epineurium of intact rat sciatic nerve. Results of histological examination of sciatic nerve and multiplex immunoassays of serum showed the absence of immunogenicity and biosafety of plasmid рBud-coVEGF165-coFGF2. Moreover, local administration of plasmid DNA construct resulted in significantly decreased levels of pro-inflammatory cytokines in the peripheral blood, including tumor necrosis factor α(TNFα) and interleukin-12, and significantly increased levels of cytokines and chemokines including Regulated upon Activation, Normal T Cell Expressed and Presumably Secrete(RANTES), epidermal growth factor, interleukin-2, and monocyte chemoattractant protein 1. These changes in the peripheral blood on day 7 after injection of plasmid construct рBud-coVEGF165-coFGF2 show that the plasmid construct has systemic effects and may modulate immune response. At the same time, reverse transcriptionpolymerase chain reaction revealed transient expression of coFGF2, coVEGF165, ratFGF2 and ratVEGFA with direct transport of transcripts from distal part to proximal part of the sciatic nerve. Immunohistochemical staining revealed prolonged presence of VEGFA in sciatic nerve till 14 days post-injection. These findings suggest that local administration of plasmid construct рBud-coVEGF165-coFGF2 at a concentration of 30 ng/μL results in the formation of pro-angiogenic stimuli and, and the plasmid construct, used as a drug for gene therapy, might potentially facilitate regeneration of the sciatic nerve. The study was approved by the Animal Ethics Committee of Kazan Federal University, procedures were approved by the Local Ethics Committee(approval No. 5) on May 27, 2014.

International recognition of the Ilizarov bone reconstruction techniques: Current practice and research (dedicated to 100th birthday of G. A. Ilizarov)

The Ilizarov method is one of the current methods used in bone reconstruction.It originated in the middle of the past century and comprises a number of bone reconstruction techniques executed with a ring external fixator developed by Ilizarov GA.Its main merits are viable new bone formation through distraction osteogenesis,high union rates and functional use of the limb throughout the course of treatment.The study of the phenomenon of distraction osteogenesis induced by tension stress with the Ilizarov apparatus was the impetus for advancement in bone reconstruction surgery.Since then,the original method has been used along with a number of its modifications developed due to emergence of new fixation devices and techniques of their application such as hexapod external fixators and motorized intramedullary lengthening nails.They gave rise to a relatively new orthopedic subspecialty termed“limb lengthening and reconstruction surgery”.Based on a comprehensive literature search,we summarized the recent clinical practice and research in bone reconstruction by the Ilizarov method with a special focus on its modification and recognition by the world orthopedic community.The international influence of the Ilizarov method was reviewed in regard to the origin country of the authors and journal’s rating.The Ilizarov method and other techniques based on distraction osteogenesis have been used in many countries and on all populated continents.It proves its international significance and confirms the greatest contribution of Ilizarov GA to bone reconstruction surgery.

Surface-based map plasticity of brain regions related to sensory motor and pain information processing after osteonecrosis of the femoral head

Pain is one of the manifestations of hip disorder and has been proven to lead to the remodeling of somatotopic map plasticity in the cortex.However,most studies are volume-based which may lead to inaccurate anatomical positioning of functional data.The methods that work on the cortical surface may be more sensitive than those using the full brain volume and thus be more suitable for map plasticity study.In this prospective cross-sectional study performed in Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,China,20 patients with osteonecrosis of the femoral head(12 males and 8 females,aged 56.80±13.60 years)and 20 healthy controls(9 males and 11 females,aged 54.56±10.23 years)were included in this study.Data of resting-state functional magnetic resonance imaging were collected.The results revealed that compared with healthy controls,compared with the healthy controls,patients with osteonecrosis of the femoral head(ONFH)showed significantly increased surface-based regional homogeneity(Re Ho)in areas distributed mainly in the left dorsolateral prefrontal cortex,frontal eye field,right frontal eye field,and the premotor cortex and decreased surface-based Re Ho in the right primary motor cortex and primary sensory cortex.Regions showing significant differences in surfacebased Re Ho values between the healthy controls and patients with ONFH were defined as the regions of interests.Seed-based functional connectivity was performed to investigate interregional functional synchronization.When the areas with decreased surface-based Re Ho in the frontal eye field and right premotor cortex were used as the regions of interest,compared with the healthy controls,the patients with ONFH displayed increased functional connectivity in the right middle frontal cortex and right inferior parietal cortex and decreased functional connectivity in the right precentral cortex and right middle occipital cortex.Compared with healthy controls,patients with ONFH showed significantly decreased cortical thickness in the para-insular area,posterior insular area,anterior superior temporal area,frontal eye field and supplementary motor cortex and reduced volume of subcortical gray matter nuclei in the right nucleus accumbens.These findings suggest that hip disorder patients showed cortical plasticity changes,mainly in sensorimotor-and pain-related regions.This study was approved by the Medical Ethics Committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine(approval No.2018-041)on August 1,2018.

Effects of paired associative magnetic stimulation between nerve root and cortex on motor function of lower limbs after spinal cord injury:study protocol for a randomized controlled trial

Classic paired associative stimulation can improve synaptic plasticity,as demonstrated by animal expe riments and human clinical trials in spinal cord injury patients.Paired associative magnetic stimulation(dual-target peripheral and central magnetic stimulation)has been shown to promote neurologic recove ry after stroke.However,it remains unclear whether paired associative magnetic stimulation can promote recovery of lower limb motor dysfunction after spinal cord injury.We hypothesize that the curre nt caused by central and peripheral magnetic stimulation will conve rge at the synapse,which will promote synapse function and improve the motor function of the relevant muscles.Therefore,this study aimed to examine the effects of paired associative magnetic stimulation on neural circuit activation by measuring changes in motor evoked and somatosensory evoked potentials,motor and sensory function of the lower limbs,functional health and activities of daily living,and depression in patients with spinal co rd injury.We will recruit 110 thora cic spinal trauma patients treated in the Department of Spinal Cord Injury,China Rehabilitation Hospital and randomly assign them to expe rimental and control groups in a 1:1 ratio.The trial group(n=55)will be treated with paired associative magnetic stimulation and conventional rehabilitation treatment.The control group(n=55)will be treated with sham stimulation and co nventional rehabilitation treatment.Outcomes will be measured at four time points:baseline and 4,12,and 24 wee ks after the start of inte rvention(active or sham paired associative magnetic stimulation).The primary outcome measure of this trial is change in lower limb American Spinal Injury Association Impairment Scale motor function score from baseline to last follow-up.Secondary outcome measures include changes in lower limb American Spinal Injury Association sensory function sco re,motor evoked potentials,sensory evoked potentials,modified Ashwo rth scale score,Maslach Burnout Invento ry score,and Hamilton Depression Scale score over time.Motor evoked potential latency reflects corticospinal tract transmission time,while amplitude reflects recruitment ability;both measures can help elucidate the mechanism underlying the effect of paired associative magnetic stimulation on synaptic efficiency.Adve rse events will be recorded.Findings from this trial will help to indicate whether paired associative magnetic stimulation(1)promotes recove ry of lower limb sensory and motor function,reduces spasticity,and improves quality of life;(2)promotes neurologic recovery by increasing excitability of spinal cord motor neurons and stimulating synaptic plasticity;and(3)improves rehabilitation outcome in patients with spinal cord injury.Recruitment for this trial began in April 2021 and is currently ongoing.It was approved by the Ethics Committee of Yangzhi Affiliated Rehabilitation Hospital of Tongji University,China(approval No.YZ2020-018)on May 18,2020.The study protocol was registered in the Chinese Clinical Trial Registry(registration number:ChiCTR2100044794)on March 27,2021(protocol version 1.0).This trial will be completed in April 2022.

Step-by-step external fixation of unstable pelvis with separate anterior and posterior modules

Objective: To evaluate the treatment outcomes of patients with pelvic ring injury by applying step-by-step external pelvic fixation and circular external fixation device.Methods: A total of 28 patients suffering from disintegrated pelvic ring injury are involved in the study. Fourteen patients(the treatment group) underwent step-by-step external pelvic fixation by applying anterior(anti-shock) and posterior modules. For the rest 14 patients(the experimental group), the osteosynthesis were conducted by means of a circular external fixation device. The long-term outcomes were evaluated in a year after the injury.Results: The residual deformity of 5(4–7) mm was observed in 10 patients(71.4%) from the experimental group. In the treatment group, the residual deformity was evident only in 4(28.6%) cases being 2.5(2–3) mm(P = 0.000 319) on the average. The functional result(according to the Majeed scale) was statistically better in the treatment group(P = 0.000 319). Nine(64.3%) and five(35.7%) patients in treatment group showed excellent and positive results, respectively. The excellent result was demonstrated by 3patients(21.4%) of the experimental group, the positive outcomes were observed in 6 cases(42.9%) and the unsatisfactory one was displayed by 1 patient(7.1%) of the same group.Conclusions: The modular approach applied is the advantage of the transosseous osteosynthesis allowing for a separate anterior(anti-shock) fixation and final posterior reposition of the pelvic ring preceded by the stabilization of vital functions. The above mentioned method gives an opportunity to increase the amount of techniques applied for the pelvic external fixation in polytrauma cases.

Recurrent Dermatofibrosarcoma Protuberant of the Hand: A Case Report

Dermatofibrosarcoma is a rare, slow growing tumor with a tendency to local recurrence. The treatment is mainly surgical. In Madagascar there is no specialized center for the management of soft tissue sarcomas. It is in this context that we report a case of a 45-year-old man, driver, presenting with recurrent dermatofibrosarcoma of the left hand. The diagnosis was confirmed by the positivity of the CD34 marker. Extensive local excision surgery was performed with the patient’s consent. After free years of treatment, there is no tumor recurrence.

Modified constraint-induced movement therapy enhances cortical plasticity in a rat model of traumatic brain injury:a resting-state functional MRI study

Modified constraint-induced movement therapy(mCIMT)has shown beneficial effects on motor function improvement after brain injury,but the exact mechanism remains unclear.In this study,amplitude of low frequency fluctuation(ALFF)metrics measured by resting-state functional magnetic resonance imaging was obtained to investigate the efficacy and mechanism of mCIMT in a control co rtical impact(CCI)rat model simulating traumatic brain injury.At 3 days after control co rtical impact model establishment,we found that the mean ALFF(mALFF)signals were decreased in the left motor cortex,somatosensory co rtex,insula cortex and the right motor co rtex,and were increased in the right corpus callosum.After 3 weeks of an 8-hour daily mClMT treatment,the mALFF values were significantly increased in the bilateral hemispheres compared with those at 3 days postoperatively.The mALFF signal valu es of left corpus callosum,left somatosensory cortex,right medial prefro ntal cortex,right motor co rtex,left postero dorsal hippocampus,left motor cortex,right corpus callosum,and right somatosensory cortex were increased in the mCIMT group compared with the control cortical impact group.Finally,we identified brain regions with significantly decreased mALFF valu es at 3 days postoperatively.Pearson correlation coefficients with the right forelimb sliding score indicated that the improvement in motor function of the affected upper limb was associated with an increase in mALFF values in these brain regions.Our findings suggest that functional co rtical plasticity changes after brain injury,and that mCIMT is an effective method to improve affected upper limb motor function by promoting bilateral hemispheric co rtical remodeling.mALFF values correlate with behavio ral changes and can potentially be used as biomarkers to assess dynamic cortical plasticity after traumatic brain injury.

Resting-state brain network remodeling after different nerve reconstruction surgeries:a functional magnetic resonance imaging study in brachial plexus injury rats

Distinct brain remodeling has been found after different nerve reconstruction strategies,including motor representation of the affected limb.However,differences among reconstruction strategies at the brain network level have not been elucidated.This study aimed to explore intranetwork changes related to altered peripheral neural pathways after different nerve reconstruction surgeries,including nerve repair,endto-end nerve transfer,and end-to-side nerve transfer.Sprague–Dawley rats underwent complete left brachial plexus transection and were divided into four equal groups of eight:no nerve repair,grafted nerve repair,phrenic nerve end-to-end transfer,and end-to-side transfer with a graft sutured to the anterior upper trunk.Resting-state brain functional magnetic resonance imaging was obtained 7 months after surgery.The independent component analysis algorithm was utilized to identify group-level network components of interest and extract resting-state functional connectivity values of each voxel within the component.Alterations in intra-network resting-state functional connectivity were compared among the groups.Target muscle reinnervation was assessed by behavioral observation(elbow flexion)and electromyography.The results showed that alterations in the sensorimotor and interoception networks were mostly related to changes in the peripheral neural pathway.Nerve repair was related to enhanced connectivity within the sensorimotor network,while end-to-side nerve transfer might be more beneficial for restoring control over the affected limb by the original motor representation.The thalamic-cortical pathway was enhanced within the interoception network after nerve repair and end-to-end nerve transfer.Brain areas related to cognition and emotion were enhanced after end-to-side nerve transfer.Our study revealed important brain networks related to different nerve reconstructions.These networks may be potential targets for enhancing motor recovery.

Academic Stress Assessment Using Virtual Reality as an Educational Tool in Spine Surgery

Introduction: The evaluation of academic stress in medical students and residents is a topic of significant interest, given the considerable challenges they face during their learning process with traditional teaching methods. The use of technologies like virtual reality presents an opportunity to enhance their skills through simulations and training. The main objective of this study is to qualitatively assess the stress levels experienced by medical students and residents by integrating virtual reality into their current learning methods, aiming to improve their ability to manage stressors in their practice. Material and Methods: A questionnaire was conducted with 12 medical students and 12 Traumatology and orthopedics residents. The purpose of the questionnaire was to evaluate the levels of academic stress using the SISCO inventory. The stress levels were calculated by transforming average values into percentages, and the following criteria were assigned: 0 to 33% for Mild Stress, 34 to 66% for Moderate Stress, and 67 to 100% for Deep Stress. Then, a virtual reality class focused on spine surgery was provided. Both medical students and residents were trained using the Non Nocere SharpSurgeon software platform and Oculus Quest 2 virtual reality glasses. At the end of the session, a second questionnaire related to the practice with virtual reality was conducted with the same evaluation criteria and a comparative analysis was carried out. Results: 12 undergraduate students from Hospital Angeles Mexico, CDMX and 12 traumatology and orthopedics residents at Hospital Santa Fe, Bogota were evaluated. The students in CDMX reported an average qualitative stress of 28.50% during habitual practices, which decreased to an average of 14.67% after virtual reality practice. Residents in Bogotá experienced an average qualitative stress of 30.50% with their current learning methods but this reduced to an average of 13.92% after using virtual reality. These findings indicate that the use of virtual reality has a positive impact on reducing stress levels qualitatively. Conclusions: The use of virtual reality as a learning method for medical students and residents qualitatively improves stress levels. Further studies are required to define the potential uses of Virtual Reality to improve learning methods and emotional state in medical students and residents and for a quantitative assessment to validate the training as certified learning methods.

Electroacupuncture treatment improves motor function and neurological outcomes after cerebral ischemia/reperfusion injury

Electroacupuncture(EA)has been widely used for functional restoration after stroke.However,its role in post-stroke rehabilitation and the associated regulatory mechanisms remain poorly understood.In this study,we applied EA to the Zusanli(ST36)and Quchi(LI11)acupoints in rats with middle cerebral artery occlusion and reperfusion.We found that EA effectively increased the expression of brain-derived neurotrophic factor and its receptor tyrosine kinase B,synapsin-1,postsynaptic dense protein 95,and microtubule-associated protein 2 in the ischemic penumbra of rats with middle cerebral artery occlusion and reperfusion.Moreover,EA greatly reduced the expression of myelin-related inhibitors Nogo-A and NgR in the ischemic penumbra.Tyrosine kinase B inhibitor ANA-12 weakened the therapeutic effects of EA.These findings suggest that EA can improve neurological function after middle cerebral artery occlusion and reperfusion,possibly through regulating the activity of the brain-derived neurotrophic factor/tyrosine kinase B signal pathway.All procedures and experiments were approved by the Animal Research Committee of Shanghai University of Traditional Chinese Medicine,China(approval No.PZSHUTCM200110002)on January 10,2020.

Altered intra- and inter-network brain functional connectivity in upper-limb amputees revealed through independent component analysis

Although cerebral neuroplasticity following amputation has been observed, little is understood about how network-level functional reorganization occurs in the brain following upper-limb amputation. The objective of this study was to analyze alterations in brain network functional connectivity(FC) in upper-limb amputees(ULAs). This observational study included 40 ULAs and 40 healthy control subjects;all participants underwent resting-state functional magnetic resonance imaging. Changes in intra-and inter-network FC in ULAs were quantified using independent component analysis and brain network FC analysis. We also analyzed the correlation between FC and clinical manifestations, such as pain. We identified 11 independent components using independent component analysis from all subjects. In ULAs, intra-network FC was decreased in the left precuneus(precuneus gyrus) within the dorsal attention network and left precentral(precentral gyrus) within the auditory network;but increased in the left Parietal_Inf(inferior parietal, but supramarginal and angular gyri) within the ventral sensorimotor network, right Cerebelum_Crus2(crus Ⅱ of cerebellum) and left Temporal_Mid(middle temporal gyrus) within the ventral attention network, and left Rolandic_Oper(rolandic operculum) within the auditory network. ULAs also showed decreased inter-network FCs between the dorsal sensorimotor network and ventral sensorimotor network, the dorsal sensorimotor network and right frontoparietal network, and the dorsal sensorimotor network and dorsal attention network. Correlation analyses revealed negative correlations between inter-network FC changes and residual limb pain and phantom limb pain scores, but positive correlations between inter-network FC changes and daily activity hours of stump limb. These results show that post-amputation plasticity in ULAs is not restricted to local remapping;rather, it also occurs at a network level across several cortical regions. This observation provides additional insights into the plasticity of brain networks after upper-limb amputation, and could contribute to identification of the mechanisms underlying post-amputation pain.

Clinical effect of scraping therapy in the treatment of knee osteoarthritis

Objective:The objective of this study is to investigate the effect of scraping therapy in the treatment of knee osteoarthritis.Materials and Methods:A total of eighty patients with knee osteoarthritis were assigned to the moxibustion group and the scraping therapy group according to the random numerical table method,with forty cases in each group.Patients in both two groups received functional exercise and moxibustion therapy,and those in the scraping therapy group were supplemented with scraping therapy.The serum indexes of interleukin‑1(IL‑1),IL‑6,tumor necrosis factor‑alpha(TNF‑α),and superoxide dismutase(SOD)were detected before and after the treatment.The clinical syndrome integral and Visual Analog Scale(VAS)on pain of patients were assessed.The clinical therapeutic efficacy was evaluated and compared between the two groups.Results:Patients in the scraping therapy group received better outcomes of serum IL‑1,IL‑6,TNF‑α,and SOD compared with those in the moxibustion group at 2 months after treatment(P<0.05).The scores of clinical syndrome integral and VAS on pain were decreased in two groups at 2 months after the treatment and were lower in the scraping therapy group than those in the moxibustion group(P<0.05).The overall effective rate in the scraping therapy group was higher than that in the control group(87.50%vs.67.50%,P<0.05).Conclusion:The scraping therapy is potentially effective to ameliorate the clinical symptom and pain degree of patients with knee osteoarthritis.

Technique of Granulation Tissue Genesis from Diploe

Introduction: Many techniques are used in surgery for importing scalp losses. Microsurgery reinsertion dominates these techniques. When reinsertion is not possible, other alternatives are available. Among these is the production of the granulation tissue by diploic perforation. Many authors have reported this technic without explaining the physiological mechanisms that contribute to the genesis of this granulation tissue from the diploe. We intend to recall them. Patients and Methods: This was a series of 3 cases supported for significant loss of the scalp. The technic consisted in making trepan drill holes and carrying the outer table to the diploe by using a Doyen drill. Then fat dressings were applied every other day until the formation of granulation tissue over the entire loss of tissue surface. Observations: Three patients benefited from this technique, 2 traumatic and the other one iatrogenic after a scalp tumor excision. The missing area of traumatic wounds was estimated at 18 and 25 cm2 respectively. The third patient had a loss of scalp after surgical removal of an ulcerous-budding tumor of the scalp without any impacting the skull. Granulation tissue was obtained in all cases after an average of 30 days. There was no infection. Two patients were grafted with favorable progress and one patient went under indirect wound healing. Conclusion: The ability of the diploe to generate granulation tissue is due to its intrinsic anatomical and functional potentialities. This is a technic of last resort when conventional reconstructive surgery is contraindicated for several reasons.

In vitro chondrogenesis of the goat bone marrow mesenchymal stem cells directed by chondrocytes in monolayer and 3-dimetional indirect co-culture system

Background Cartilage injury has a very poor capacity for intrinsic regeneration. The cell-based treatment strategy for the cartilage repair using differentiated bone marrow mesenchymal stem cells （BMSCs） is, however, a promising approach to the chondral repair. This study was aimed to explore the chondrogenic potential of the goat BMSCs in the Transwell co-culture system and the poly-laetide-co-glycolide （PLGA） scaffolds.Methods The BMSCs were isolated from the goat iliac crest while the chondrocytes were obtained from the goat＇s last costal cartilage. In the Transwell co-culture system, the BMSCs co-cultured with chondrocytes were designed as group A,whereas the goat＇s BMSCs induced with the chondrogenic medium were group B. Both groups A and B were the experimental groups, while group C that only contained BMSCs was the control group. In the PLGA scaffolds co-culture system, BMSCs were seeded into the PLGA scaffolds, which were suspended in the 24-well plate, and the control group was established by presence or absence of chondrocytes at the bottom of the 24-well plate. Toluidine blue staining,Alcian blue staining, collagen Ⅱ immunofluoresence, collagen Ⅱ immunochemical staining, collagen Ⅰ, collagen Ⅱ, COL2a Q-PCR and osteopontin Q-PCR were used to examine the chondrogenic conditions as well as the expressions of chondrogenic and osteogenic genes.Results Cells isolated from the aspirates of the goat bone marrow proliferated rapidly and gained characteristics of stem cells in Passage 4. However, the differentiations of chondrocytes were not apparent in Passage 3. The results from Toluidine blue staining, collagen Ⅱ immunofluoresence and PCR showed the transformation of BMSCs to chondrocytes in the Transwell co-culture system and PLGA scaffolds. Although the cartilage gene expressions were upgraded in both chondrogenesis group and co-culture system, the osteopontin gene expression, which represents osteogenic level, was also up-regulated.Conclusions The Transwell co-culture system and the PLGA scaffolds co-culture system can promote the chondrogenic differentiation of the goat＇s BMSCs, while up-regulated osteopontin gene expression in the Transwell co-culture system implies the osteogenic potential of BMSCs.

Brain plasticity after peripheral nerve injury treatment with massage therapy based on resting-state functional magnetic resonance imaging

Massage therapy is an alternative treatment for chronic pain that is potentially related to brain plasticity.However,the underlying mechanism remains unclear.We established a peripheral nerve injury model in rats by unilateral sciatic nerve transection and direct anastomosis.The experimental rats were treated over the gastrocnemius muscle of the affected hindlimb with a customized massage instrument(0.45 N,120 times/min,10 minutes daily,for 4 successive weeks).Resting-state functional magnetic resonance imaging revealed that compared with control rats,the amplitude of low-frequency fluctuations in the sensorimotor cortex contralateral to the affected limb was significantly lower after sciatic nerve transection.However,amplitudes were significantly higher in the massage group than in a sham-massage group.These findings suggest that massage therapy facilitated adaptive change in the somatosensory cortex that led to the recovery of peripheral nerve injury and repair.This study was approved by the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine of China(approval No.201701001)on January 12,2017.

Tanshinone IIa antagonizes spinal ischemia/reperfusion injury by interfering with upstream glutamic acid factors

Based on the hypothesis that upstream factor inhibition results in better treatment effects than downstream factor inhibition,the present study interfered with glutamic acid（Glu）-released upstream factors,such as Glu transporter function and Na＋-K＋-adenosine triphosphatases（ATPase）activity relativly.Rats with spinal cord ischemia/reperfusion injury received intraperitoneal injections of tanshinone Ila and Glu uptake and Na＋-K＋-ATPase activity were increased.Results showed that tanshinone Ila influenced Glu-released upstream factors following spinal ischemia/reperfusion injury and protected against spinal ischemia/reperfusion injury.

Development and internal validation of China mortality prediction model in trauma based on ICD-10-CM lexicon:CMPMIT-ICD10

Background:Models to predict mortality in trauma play an important role in outcome prediction and severity adjustment,which informs trauma quality assessment and research.Hospitals in China typically use the International Classification of Diseases,Tenth Revision,Clinical Modification(ICD-10-CM)to describe injury.However,there is no suitable prediction model for China.This study attempts to develop a new mortality prediction model based on the ICD-10-CM lexicon and a Chinese database.Methods:This retrospective study extracted the data of all trauma patients admitted to the Beijing Red Cross Emergency Center,from January 2012 to July 2018(«=40,205).We used relevant predictive variables to establish a prediction model following logistic regression analysis.The performance of the model was assessed based on discrimination and calibration.The bootstrapping method was used for internal validation and adjustment of model performance.Results:Sex,age,new region-severity codes,comorbidities,traumatic shock,and coma were finally included in the new model as key predictors of mortality.Among them,coma and traumatic shock had the highest scores in the model.The discrimination and calibration of this model were significant,and the internal validation performance was good.The values of the area under the curve and Brier score for the new model were 0.9640 and 0.0177,respectively;after adjustment of the bootstrapping method,they were 0.9630 and 0.0178,respectively.Conclusions:The new model(China Mortality Prediction Model in Trauma based on the ICD-10-CM lexicon)showed great discrimination and calibration,and performed well in internal validation;it should be further verified externally.

Expert consensus on management principles of orthopedic emergency in the epidemic of coronavirus disease 2019

Since December 2019,many patients in Wuhan sustained pneumonia with unknown causes.[1,2]A part of severe patients developed acute respiratory distress syndrome or septic shock,and even death.On January 7,2020,Chinese researchers have for the first time detected a new coronavirus.On January 20,2020,the National Health Commission issued Announcement No.1 of 2020,which included the new coronavirus pneumonia as a Class B infectious disease,and conducted epidemic prevention and control according to the Class A infectious disease.This new kind of pneumonia has been named coronavirus disease 2019(COVID-19).The sixth edition of"Diagnosis and Treatment Scheme for New Coronavirus Infected Pneumonia"points out that the main transmission routes include respiratory droplets and close contact transmission.There is a possibility of aerosol transmission in a relatively closed environment with prolonged exposure to high concentrations of aerosol.New coronavirus pneumonia has a certain incubation period.