Repair and regeneration of peripheral nerve injuries that ablate branch points

The peripheral nervous system has an extensive branching organization, and peripheral nerve injuries that ablate branch points present a complex challenge for clinical repair. Ablations of linear segments of the PNS have been extensively studied and routinely treated with autografts, acellular nerve allografts, conduits, wraps, and nerve transfers. In contrast, segmental-loss peripheral nerve injuries, in which one or more branch points are ablated so that there are three or more nerve endings, present additional complications that have not been rigorously studied or documented. This review discusses:(1) the branched anatomy of the peripheral nervous system,(2) case reports describing how peripheral nerve injuries with branched ablations have been surgically managed,(3) factors known to influence regeneration through branched nerve structures,(4) techniques and models of branched peripheral nerve injuries in animal models, and(5) conclusions regarding outcome measures and studies needed to improve understanding of regeneration through ablated branched structures of the peripheral nervous system.

Role of transforming growth factor-βin peripheral nerve regeneration

Injuries caused by trauma and neurodegenerative diseases can damage the peripheral nervous system and cause functional deficits.Unlike in the central nervous system,damaged axons in peripheral nerves can be induced to regenerate in response to intrinsic cues after reprogramming or in a growth-promoting microenvironment created by Schwann cells.However,axon regeneration and repair do not automatically result in the restoration of function,which is the ultimate therapeutic goal but also a major clinical challenge.Transforming growth factor(TGF)is a multifunctional cytokine that regulates various biological processes including tissue repair,embryo development,and cell growth and differentiation.There is accumulating evidence that TGF-βfamily proteins participate in peripheral nerve repair through various factors and signaling pathways by regulating the growth and transformation of Schwann cells;recruiting specific immune cells;controlling the permeability of the blood-nerve barrier,thereby stimulating axon growth;and inhibiting remyelination of regenerated axons.TGF-βhas been applied to the treatment of peripheral nerve injury in animal models.In this context,we review the functions of TGF-βin peripheral nerve regeneration and potential clinical applications.

Neutrophil peptide 1 accelerates the clearance of degenerative axons during Wallerian degeneration by activating macrophages after peripheral nerve crush injury

Macrophages play an important role in peripheral nerve regeneration,but the specific mechanism of regeneration is still unclear.Our preliminary findings indicated that neutrophil peptide 1 is an innate immune peptide closely involved in peripheral nerve regeneration.However,the mechanism by which neutrophil peptide 1 enhances nerve regeneration remains unclear.This study was designed to investigate the relationship between neutrophil peptide 1 and macrophages in vivo and in vitro in peripheral nerve crush injury.The functions of RAW 264.7 cells we re elucidated by Cell Counting Kit-8 assay,flow cytometry,migration assays,phagocytosis assays,immunohistochemistry and enzyme-linked immunosorbent assay.Axonal debris phagocytosis was observed using the CUBIC(Clear,Unobstructed Brain/Body Imaging Cocktails and Computational analysis)optical clearing technique during Wallerian degeneration.Macrophage inflammatory factor expression in different polarization states was detected using a protein chip.The results showed that neutrophil peptide 1 promoted the prolife ration,migration and phagocytosis of macrophages,and CD206 expression on the surfa ce of macrophages,indicating M2 polarization.The axonal debris clearance rate during Wallerian degeneration was enhanced after neutrophil peptide 1 intervention.Neutrophil peptide 1 also downregulated inflammatory factors interleukin-1α,-6,-12,and tumor necrosis factor-αin invo and in vitro.Thus,the results suggest that neutrophil peptide 1 activates macrophages and accelerates Wallerian degeneration,which may be one mechanism by which neutrophil peptide 1 enhances peripheral nerve regeneration.

Chemokine platelet factor 4 accelerates peripheral nerve regeneration by regulating Schwann cell activation and axon elongation

Schwann cells in peripheral nerves react to traumatic nerve injury by attempting to grow and regenerate.Howeve r,it is unclear what factors play a role in this process.In this study,we searched a GEO database and found that expression of platelet factor 4 was markedly up-regulated after sciatic nerve injury.Platelet factor is an important molecule in cell apoptosis,diffe rentiation,survival,and proliferation.Further,polymerase chain reaction and immunohistochemical staining confirmed the change in platelet factor 4 in the sciatic nerve at different time points after injury.Enzyme-linked immunosorbent assay confirmed that platelet factor 4 was secreted by Schwann cells.We also found that silencing platelet factor 4 decreased the proliferation and migration of primary cultured Schwann cells,while exogenously applied platelet factor 4 stimulated Schwann cell prolife ration and migration and neuronal axon growth.Furthermore,knocking out platelet factor 4 inhibited the prolife ration of Schwann cells in injured rat sciatic nerve.These findings suggest that Schwann cell-secreted platelet factor 4 may facilitate peripheral nerve repair and regeneration by regulating Schwann cell activation and axon growth.Thus,platelet factor 4 may be a potential therapeutic target for traumatic peripheral nerve injury.

Artificial intelligence-assisted repair of peripheral nerve injury: a new research hotspot and associated challenges

Artificial intelligence can be indirectly applied to the repair of peripheral nerve injury.Specifically,it can be used to analyze and process data regarding peripheral nerve injury and repair,while study findings on peripheral nerve injury and repair can provide valuable data to enrich artificial intelligence algorithms.To investigate advances in the use of artificial intelligence in the diagnosis,rehabilitation,and scientific examination of peripheral nerve injury,we used CiteSpace and VOSviewer software to analyze the relevant literature included in the Web of Science from 1994–2023.We identified the following research hotspots in peripheral nerve injury and repair:(1)diagnosis,classification,and prognostic assessment of peripheral nerve injury using neuroimaging and artificial intelligence techniques,such as corneal confocal microscopy and coherent anti-Stokes Raman spectroscopy;(2)motion control and rehabilitation following peripheral nerve injury using artificial neural networks and machine learning algorithms,such as wearable devices and assisted wheelchair systems;(3)improving the accuracy and effectiveness of peripheral nerve electrical stimulation therapy using artificial intelligence techniques combined with deep learning,such as implantable peripheral nerve interfaces;(4)the application of artificial intelligence technology to brain-machine interfaces for disabled patients and those with reduced mobility,enabling them to control devices such as networked hand prostheses;(5)artificial intelligence robots that can replace doctors in certain procedures during surgery or rehabilitation,thereby reducing surgical risk and complications,and facilitating postoperative recovery.Although artificial intelligence has shown many benefits and potential applications in peripheral nerve injury and repair,there are some limitations to this technology,such as the consequences of missing or imbalanced data,low data accuracy and reproducibility,and ethical issues(e.g.,privacy,data security,research transparency).Future research should address the issue of data collection,as large-scale,high-quality clinical datasets are required to establish effective artificial intelligence models.Multimodal data processing is also necessary,along with interdisciplinary collaboration,medical-industrial integration,and multicenter,large-sample clinical studies.

Runx2 regulates peripheral nerve regeneration to promote Schwann cell migration and re-myelination

Runx2 is a major regulator of osteoblast differentiation and function;however,the role of Runx2 in peripheral nerve repair is unclea r.Here,we analyzed Runx2expression following injury and found that it was specifically up-regulated in Schwann cells.Furthermore,using Schwann cell-specific Runx2 knocko ut mice,we studied peripheral nerve development and regeneration and found that multiple steps in the regeneration process following sciatic nerve injury were Runx2-dependent.Changes observed in Runx2 knoc kout mice include increased prolife ration of Schwann cells,impaired Schwann cell migration and axonal regrowth,reduced re-myelination of axo ns,and a block in macrophage clearance in the late stage of regeneration.Taken together,our findings indicate that Runx2 is a key regulator of Schwann cell plasticity,and therefore peripheral nerve repair.Thus,our study shows that Runx2 plays a major role in Schwann cell migration,re-myelination,and peripheral nerve functional recovery following injury.

miRNA-21-5p is an important contributor to the promotion of injured peripheral nerve regeneration using hypoxia-pretreated bone marrow-derived neural crest cells

Our previous study found that rat bone marrow–derived neural crest cells(acting as Schwann cell progenitors)have the potential to promote long-distance nerve repair.Cell-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular communication.Nevertheless,the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain unclear.To investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves,we collected conditioned culture medium from hypoxia-pretreated neural crest cells,and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose deprivation.The mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest cells.We performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest cells.Subsequently,to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons,we used a microfluidic axonal dissociation model of sensory neurons in vitro,and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons,which was greatly dependent on loaded miR-21-5p.Finally,we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb,as well as muscle tissue morphology of the hind limbs,were obviously restored.These findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in miRNA-21-5p.miRNA-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell secretome.This helps to explain the mechanism of action of the secretome and extracellular vesicles of neural crest cells in repairing damaged peripheral nerves,and also promotes the application of miR-21-5p in tissue engineering regeneration medicine.

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

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.

Epithelioid malignant peripheral nerve sheath tumor of the bladder and concomitant urothelial carcinoma: A case report

BACKGROUND Epithelioid malignant peripheral nerve sheath tumor(EMPNST)of the bladder is a rare entity with devastating features.These tumors are thought to originate from malignant transformation of pre-existing schwannomas of pelvic autonomic nerve plexuses,and unlike the conventional malignant peripheral nerve sheath tumor(MPNST),are not associated with neurofibromatosis.The tumor has dis-tinctive morphological,immunohistochemical and molecular features.Addi-tionally,it tends to be more aggressive and have a higher mortality.This is the first case that presents with a synchronous urothelial carcinoma of the bladder and the epithelioid variant of MPNST in the literature.It’s also the second re-ported case of EMPNST originating from the bladder wall.CASE SUMMARY In this case report,we present the detailed clinical course of a 71-year-old patient with EMPNST of the bladder alongside a literature review.CONCLUSION During the management of EMPNST cases,offering aggressive treatment moda-lities to the patient,such as radical cystectomy,is appropriate for the best chance to contain the disease,regardless of the tumor stage and the extent of local disease at initial diagnosis.

GDNF to the rescue:GDNF delivery effects on motor neurons and nerves,and muscle re-innervation after peripheral nerve injuries

Peripheral nerve injuries commonly occur due to trauma,like a traffic accident.Peripheral nerves get severed,causing motor neuron death and potential muscle atrophy.The current golden standard to treat peripheral nerve lesions,especially lesions with large(≥3 cm)nerve gaps,is the use of a nerve autograft or reimplantation in cases where nerve root avulsions occur.If not tended early,degeneration of motor neurons and loss of axon regeneration can occur,leading to loss of function.Although surgical procedures exist,patients often do not fully recover,and quality of life deteriorates.Peripheral nerves have limited regeneration,and it is usually mediated by Schwann cells and neurotrophic factors,like glial cell line-derived neurotrophic factor,as seen in Wallerian degeneration.Glial cell line-derived neurotrophic factor is a neurotrophic factor known to promote motor neuron survival and neurite outgrowth.Glial cell line-derived neurotrophic factor is upregulated in different forms of nerve injuries like axotomy,sciatic nerve crush,and compression,thus creating great interest to explore this protein as a potential treatment for peripheral nerve injuries.Exogenous glial cell line-derived neurotrophic factor has shown positive effects in regeneration and functional recovery when applied in experimental models of peripheral nerve injuries.In this review,we discuss the mechanism of repair provided by Schwann cells and upregulation of glial cell line-derived neurotrophic factor,the latest findings on the effects of glial cell line-derived neurotrophic factor in different types of peripheral nerve injuries,delivery systems,and complementary treatments(electrical muscle stimulation and exercise).Understanding and overcoming the challenges of proper timing and glial cell line-derived neurotrophic factor delivery is paramount to creating novel treatments to tend to peripheral nerve injuries to improve patients'quality of life.

The Construction of Integrated Nursing Model Prevention of Oxaliplatin Chemotherapy-Induced Peripheral Nerve Injury

Objective: To investigate the effect of the integrated nursing model in the prevention of chemotherapy-induced peripheral injury. Methods: A total of 60 tumor patients receiving oxaliplatin for 1 - 6 cycles of chemotherapy from January to September 2023 were selected. 30 patients were selected from January to March and divided into the control group, and 30 patients were selected from July to 9 as the experimental group. The control group received conventional chemotherapy nursing, while the experimental group received integrated nursing. Anxiety, peripheral nerve toxicity stage and quality of life score were compared between the two groups before and after intervention. Results: After intervention, the scores of the self-rating Anxiety Scale (SAS) and the total scores of the oxaliplatin Levi specific sensory neurotoxicity scale in the experimental group were significantly lower than those in the control group, and the differences were statistically significant (P< 0.05);The Quality of Life Scale (FACT-G) score of cancer patients was higher than that of control group, and the difference was statistically significant (P< 0.05). Conclusion: The integrated nursing model can effectively reduce the anxiety of patients, reduce the incidence of peripheral nerve injury and improve the quality of life of patients.

Long noncoding RNA H19 regulates degeneration and regeneration of injured peripheral nerves

Our previous studies have shown that long noncoding RNA(lncRNA)H19 is upregulated in injured rat sciatic nerve during the process of Wallerian degeneration,and that it promotes the migration of Schwann cells and slows down the growth of dorsal root ganglion axons.However,the mechanism by which lncRNA H19 regulates neural repair and regeneration after peripheral nerve injury remains unclear.In this study,we established a Sprague-Dawley rat model of sciatic nerve transection injury.We performed in situ hybridization and found that at 4–7 days after sciatic nerve injury,lncRNA H19 was highly expressed.At 14 days before injury,adeno-associated virus was intrathecally injected into the L4–L5 foramina to disrupt or overexpress lncRNA H19.After overexpression of lncRNA H19,the growth of newly formed axons from the sciatic nerve was inhibited,whereas myelination was enhanced.Then,we performed gait analysis and thermal pain analysis to evaluate rat behavior.We found that lncRNA H19 overexpression delayed the recovery of rat behavior function,whereas interfering with lncRNA H19 expression improved functional recovery.Finally,we examined the expression of lncRNA H19 downstream target SEMA6D,and found that after lncRNA H19 overexpression,the SEMA6D protein level was increased.These findings suggest that lncRNA H19 regulates peripheral nerve degeneration and regeneration through activating SEMA6D in injured nerves.This provides a new clue to understand the role of lncRNA H19 in peripheral nerve degeneration and regeneration.

Security breach:peripheral nerves provide unrestricted access for toxin delivery into the central nervous system

We explore the hypothesis that a potential explanation for the initiation of motor neuron disease is an unappreciated vulnerability in central nervous system defense,the direct delivery of neurotoxins into motor neurons via peripheral nerve retrograde transport.This further suggests a mechanism for focal initiation of neuro-degenerative diseases in general,with subsequent spread by network degeneration as suggested by the Frost-Diamond hypothesis.We propose this vulnerability may be a byproduct of vertebrate evolution in a benign aquatic environment,where external surfaces were not exposed to concentrated neurotoxins.

Factors predicting sensory and motor recovery after the repair of upper limb peripheral nerve injuries

OBJECTIVE： To investigate the factors associated with sensory and motor recovery after the repair of upper limb peripheral nerve injuries. DATA SOURCES： The online PubMed database was searched for English articles describing outcomes after the repair of median, ulnar, radial, and digital nerve injuries in humans with a publication date between 1 January 1990 and 16 February 2011. STUDY SELECTION： The following types of article were selected： （1） clinical trials describ- ing the repair of median, ulnar, radial, and digital nerve injuries published in English; and （2） studies that reported sufficient patient information, including age, mechanism of injury, nerve injured, injury location, defect length, repair time, repair method, and repair materials. SPSS 13.0 software was used to perform univariate and multivariate logistic regression analyses and to in- vestigate the patient and intervention factors associated with outcomes. MAIN OUTCOME MEASURES： Sensory function was assessed using the Mackinnon-Dellon scale and motor function was assessed using the manual muscle test. Satisfactory motor recovery was defined as grade M4 or M5, and satisfactory sensory recovery was defined as grade S3＋ or S4. RESULTS： Seventy-one articles were included in this study. Univariate and multivariate logistic regression analyses showed that repair time, repair materials, and nerve injured were inde- pendent predictors of outcome after the repair of nerve injuries （P 〈 0.05）, and that the nerve injured was the main factor affecting the rate of good to excellent recovery. CONCLUSION： Predictors of outcome after the repair of peripheral nerve injuries include age, gender, repair time, repair materials, nerve injured, defect length, and duration of follow-up.

An update–tissue engineered nerve grafts for the repair of peripheral nerve injuries

Peripheral nerve injuries（PNI） are caused by a range of etiologies and result in a broad spectrum of disability. While nerve autografts are the current gold standard for the reconstruction of extensive nerve damage, the limited supply of autologous nerve and complications associated with harvesting nerve from a second surgical site has driven groups from multiple disciplines, including biomedical engineering, neurosurgery, plastic surgery, and orthopedic surgery, to develop a suitable or superior alternative to autografting. Over the last couple of decades, various types of scaffolds, such as acellular nerve grafts（ANGs）, nerve guidance conduits, and non-nervous tissues, have been filled with Schwann cells, stem cells, and/or neurotrophic factors to develop tissue engineered nerve grafts（TENGs）. Although these have shown promising effects on peripheral nerve regeneration in experimental models, the autograft has remained the gold standard for large nerve gaps. This review provides a discussion of recent advances in the development of TENGs and their efficacy in experimental models. Specifically, TENGs have been enhanced via incorporation of genetically engineered cells, methods to improve stem cell survival and differentiation, optimized delivery of neurotrophic factors via drug delivery systems（DDS）, co-administration of platelet-rich plasma（PRP）, and pretreatment with chondroitinase ABC（Ch-ABC）. Other notable advancements include conduits that have been bioengineered to mimic native nerve structure via cell-derived extracellular matrix（ECM） deposition, and the development of transplantable living nervous tissue constructs from rat and human dorsal root ganglia（DRG） neurons. Grafts composed of non-nervous tissues, such as vein, artery, and muscle, will be briefly discussed.

Nerve autografts and tissue-engineered materials for the repair of peripheral nerve injuries: a 5-year bibliometric analysis

With advances in biomedical methods, tissue-engineered materials have developed rapidly as an alternative to nerve autografts for the repair of peripheral nerve injuries. However, the materials selected for use in the repair of peripheral nerve injuries, in particular multiple injuries and largegap defects, must be chosen carefully. Various methods and materials for protecting the healthy tissue and repairing peripheral nerve injuries have been described, and each method or material has advantages and disadvantages. Recently, a large amount of research has been focused on tissue-engineered materials for the repair of peripheral nerve injuries. Using the keywords ＂peripheral nerve injury＂, ＂autotransplant＂, ＂nerve graft＂, and ＂biomaterial＂, we retrieved publications using tissue-engineered materials for the repair of peripheral nerve injuries appearing in the Web of Science from 2010 to 2014. The country with the most total publications was the USA. The institutions that were the most productive in this field include Hannover Medical School （Germany）, Washington University （USA）, and Nantong University （China）. The total number of publications using tissue-engineered materials for the repair of peripheral nerve injuries grad- ually increased over time, as did the number of Chinese publications, suggesting that China has made many scientific contributions to this field of research.

Follow-up evaluation with ultrasonography of peripheral nerve injuries after an earthquake

Published data on earthquake-associated peripheral nerve injury is very limited. Ultrasonography has been proven to be efficient in the clinic to diagnose peripheral nerve injury. The aim of this study was to assess the role of ultrasound in the evaluation of persistent peripheral nerve injuries 1 year after the Wenchuan earthquake. Thirty-four patients with persistent clinical symptoms and neurologic signs of impaired nerve function were evaluated with sonography prior to surgi- cal repair. Among 34 patients, ultrasonography showed that 48 peripheral nerves were entrapped, and 11 peripheral nerves were disrupted. There was one case of misdiagnosis on ultrasonogra- phy. The concordance rate of ultrasonographic findings with those of surgical findings was 98%. A total of 48 involved nerves underwent neurolysis and the symptoms resolved. Only five nerves had scar tissue entrapment. Preoperative and postoperative clinical and ultrasonographic results were concordant, which verified that ultrasonography is useful for preoperative diagnosis and postoperative evaluation of injured peripheral nerves.

A 2-year follow-up survey of 523 cases with peripheral nerve injuries caused by the earthquake in Wenchuan, China

We performed a 2-year follow-up survey of 523 patients with peripheral nerve injuries caused by the earthquake in Wenchuan, Sichuan Province, China. Nerve injuries were classiifed into three types： type I injuries were nerve transection injuries, type II injuries were nerve compression injuries, and type III injuries displayed no direct neurological dysfunction due to trauma. In this study, 31 patients had type I injuries involving 41 nerves, 419 had type II injuries involving 823 nerves, and 73 had type III injuries involving 150 nerves. Twenty-two patients had open tran-section nerve injury. The restoration of peripheral nerve function after different treatments was evaluated. Surgical decompression favorably affected nerve recovery. Physiotherapy was effective for type I and type II nerve injuries, but not substantially for type III nerve injury. Pharmaco-therapy had little effect on type II or type III nerve injuries. Targeted decompression surgery and physiotherapy contributed to the effective treatment of nerve transection and compression injuries. The Louisiana State University Health Sciences Center score for nerve injury severity de-clined with increasing duration of being trapped. In the ifrst year after treatment, the Louisiana State University Health Sciences Center score for grades 3 to 5 nerve injury increased by 28.2% to 81.8%. If scores were still poor （0 or 1） after a 1-year period of treatment, further treatment was not effective.

Effect of low-frequency pulse percutaneous electric stimulation on peripheral nerve injuries at different sites

BACKGROUND： The postoperative recovery of nerve function in patients with peripheral nerve injury is always an important problem to solve after treatment. The electric stimulation induced electromagnetic field can nourish nerve, postpone muscular atrophy, and help the postoperative neuromuscular function. OBJECTIVE： To observe the effects of low-frequency pulse percutaneous electric stimulation on the functional recovery of postoperative patients with peripheral nerve injury, and quantitatively evaluate the results of electromyogram （EMG） examination before and after treatment. DESIGN ： A retrospective case analysis SETTING： The Sixth People＇s Hospital affiliated to Shanghai Jiaotong University PARTICIPANTS： Nineteen postoperative inpatients with peripheral nerve injury were selected from the De- partment of Orthopaedics, the Sixth People＇s Hospital affiliated to Shanghai Jiaotong University from June 2005 to January 2006, including 13 males and 6 females aged 24-62 years with an average of 36 years old. There were 3 cases of brachial plexus nerve injury, 3 of median nerve injury, 7 of radial nerve injury, 3 of ul- nar nerve injury and 3 of common peroneal nerve injury, and all the patients received probing nerve fiber restoration. Their main preoperative manifestations were dennervation, pain in limbs, motor and sensory disturbances. All the 19 patients were informed with the therapeutic program and items for evaluation. METHODS： ① Low-frequency pulse percutaneous electric stimulation apparatus： The patients were given electric stimulation with the TERESA cantata instrument （TERESA-0, Shanghai Teresa Health Technology, Co., Ltd.）. The patients were stimulated with symmetric square waves of 1-111 Hz, and the intensity was 1.2-5.0 mA, and it was gradually adjusted according to the recovered conditions of neural regeneration following the principle that the intensity was strong enough and the patients felt no obvious upset. They were treated for 4- 24 weeks, 10-30 minutes for each time, 1-3 times a day, and 6 weeks as a course. ② EMG examination was applied to evaluate the recoveries of recruitment, motor conduction velocity （MCV） and sensory conduction velocity （SCV） before and after treatment. The patients were examined with the EMG apparatus （DIS- A2000C, Danmark） before and after the treatment of percutaneous electric stimulation. ③Standards for evaluating the effects included cured （complete recovery of motor functions, muscle strength of grade 5, no abnormality in EMG examination）, obviously effective [general recovery of motor function, muscle strength of grade 4, no or a few denervation potentials, motor conduction velocity （MCV） and sensory conduction velocity （SCV）], improved （partial recovery of motor function, muscle strength of grade 3, denervation potentials and reinneration potentials, slowed MCV and SCV, invalid （no obvious changes of motor function）. MAIN OUTCOME MEASURES： ① Ameliorated degree of the nerve function of the postoperative patients with peripheral nerve injury treated with percutaneous electric stimulation; ② Changes of EMG examination before and after treatment. RESULTS： All the 19 postoperative patients with peripheral nerve injury were involved in the analysis of results. ① Comparison of nerve function before and after treatment in 19 patients with peripheral nerve injury of different sites： For the patients with radial nerve injury （n=7）, the nerve functions all completely recovered after 8-week treatment, and the cured and obvious rate was 100% （7/7）; For the patients with brachial plexus nerve injury （n=3）, 1 case had no obvious improvement, and the cured and obvious rate was 67% （2/3）; For the patients with common peroneal nerve injury （n=3）, the extension of foot dorsum generally recovered in 1 case of nerve contusion after 4-week treatment, and the cured and obvious rate was 67% （2/3）; For the patients with median nerve injury （n=3）, muscle strength was obviously recovered, and the cured and obvious rate was 100% （3/3）; For the patients with ulnar nerve injury （n=3）, 1 case only had recovery of partial senses, and the cured and obvious rate was 67% （2/3）. Totally 9 cases were cured, 7 were obviously effective, 1 was improved, and only 2 were invalid. After 4 courses, the cured rate of damaged nerve function after four courses was 47% （9/19）, and effective rate was 89% （17/19）.② Comparison of EMG examination before and after treatment： Before and after percutaneous electric stimulation, he effective rates of recruitment, MCV and SCV were 89% （17/19）, 58% （11/19）, 47% （9/19） respectively, and there were extremely obvious differences （P〈 0.01）. CONCLUSION： ①Low-frequency pulse percutaneous electric stimulation can improve the nerve function of postoperative patients with peripheral nerve injury of different sites, especially that the injuries of radial nerve and median nerve recover more obviously. ②Percutaneous electric stimulation can ameliorate the indexes of EMG examination, especially the recruitment, in postoperative patients with peripheral nerve injury.

Cell metabolism pathways involved in the pathophysiological changes of diabetic peripheral neuropathy

Diabetic peripheral neuropathy is a common complication of diabetes mellitus.Elucidating the pathophysiological metabolic mechanism impels the generation of ideal therapies.However,existing limited treatments for diabetic peripheral neuropathy expose the urgent need for cell metabolism research.Given the lack of comprehensive understanding of energy metabolism changes and related signaling pathways in diabetic peripheral neuropathy,it is essential to explore energy changes and metabolic changes in diabetic peripheral neuropathy to develop suitable treatment methods.This review summarizes the pathophysiological mechanism of diabetic peripheral neuropathy from the perspective of cellular metabolism and the specific interventions for different metabolic pathways to develop effective treatment methods.Various metabolic mechanisms(e.g.,polyol,hexosamine,protein kinase C pathway)are associated with diabetic peripheral neuropathy,and researchers are looking for more effective treatments through these pathways.