Surgical management of adult hand macrodactyly in a 49-year-old patient:A case report

BACKGROUND Macrodactyly is a rare congenital malformation characterized by an increase in the size of all structures of a digit,accounting for less than 1%of all congenital upper extremity conditions.CASE SUMMARY We report a case involving a 49-year-old woman who presented for the first time with untreated,radial-sided hand macrodactyly.We performed soft tissue debulking,amputation,median nerve neurotomy and coaptation,and carpal tunnel release.At the 6-year follow-up,no significant growth was observed in the bone or soft tissue of the affected area.CONCLUSION Tissue overgrowth in patients with progressive macrodactyly can continue and progress excessively with age.Median nerve neurotomy and coaptation play a crucial role in preventing recurrence of the deformity.

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.

Artificial dermis combined with skin grafting for the treatment of hand skin and soft tissue defects and exposure of bone and tendon

BACKGROUND The recovery time of hand wounds is long,which can easily result in chronic and refractory wounds,making the wounds unable to be properly repaired.The treatment cycle is long,the cost is high,and it is prone to recurrence and disability.Double layer artificial dermis combined with autologous skin transplantation has been used to repair hypertrophic scars,deep burn wounds,exposed bone and tendon wounds,and post tumor wounds.AIM To investigate the therapeutic efficacy of autologous skin graft transplantation in conjunction with double-layer artificial dermis in treating finger skin wounds that are chronically refractory and soft tissue defects that expose bone and tendon.METHODS Sixty-eight chronic refractory patients with finger skin and soft tissue defects accompanied by bone and tendon exposure who were admitted from July 2021 to June 2022 were included in this study.The observation group was treated with double layer artificial dermis combined with autologous skin graft transplantation(n=49),while the control group was treated with pedicle skin flap transplantation(n=17).The treatment status of the two groups of patients was compared,including the time between surgeries and hospital stay.The survival rate of skin grafts/flaps and postoperative wound infections were evaluated using the Vancouver Scar Scale(VSS)for scar scoring at 6 mo after surgery,as well as the sensory injury grading method and two-point resolution test to assess the recovery of skin sensation at 6 mo.The satisfaction of the two groups of patients was also compared.RESULTS Wound healing time in the observation group was significantly longer than that in the control group(P<0.05,27.92±3.25 d vs 19.68±6.91 d);there was no significant difference in the survival rate of skin grafts/flaps between the two patient groups(P>0.05,95.1±5.0 vs 96.3±5.6).The interval between two surgeries(20.0±4.3 d)and hospital stay(21.0±10.1 d)in the observation group were both significantly shorter than those in the control group(27.5±9.3 d)and(28.4±17.7 d),respectively(P<0.05).In comparison to postoperative infection(23.5%)and subcutaneous hematoma(11.8%)in the control group,these were considerably lower at(10.2%)and(6.1%)in the observation group.When comparing the two patient groups at six months post-surgery,the excellent and good rate of sensory recovery(91.8%)was significantly higher in the observation group than in the control group(76.5%)(P<0.05).There was also no statistically significant difference in two point resolution(P>0.05).The VSS score in the observation group(2.91±1.36)was significantly lower than that in the control group(5.96±1.51),and group satisfaction was significantly higher(P<0.05,90.1±6.3 vs 76.3±5.2).CONCLUSION The combination of artificial dermis and autologous skin grafting for the treatment of hand tendon exposure wounds has a satisfactory therapeutic effect.It is a safe,effective,and easy to operate treatment method,which is worthy of clinical promotion.

Chondroitinase ABC combined with Schwann cell transplantation enhances restoration of neural connection and functional recovery following acute and chronic spinal cord injury

Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal cord.Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury.We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal directions.Such Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder functions.Importantly,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord injury.These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.

Role of Vickers Ligament in the Pathogenesis of Madelung Deformity

Objective The Vickers ligament is thought to hinder the growth of palmar ulnar radius by tethering the lunate to the radius,leading to Madelung deformity.The purpose of this study was to clarify the nature of the Vickers ligament and investigate its pathogenesis in Madelung deformities based on our observation of the Vickers ligament.Methods All 22 patients(33 wrists)with Madelung deformities treated surgically between 2018 and 2022 were included.The diagnosis was confirmed radiographically in all patients.The three-dimensional computed tomography(3D-CT)data of 16 patients(19 wrists)were available.Magnetic resonance imaging(MRI)data were available for 9 patients(14 wrists).Wrist arthroscopy was used in 4 patients.The Vickers ligament was resected and submitted for histopathological examination in 8 patients.Radiographic outcomes,3D-CT,MRI,arthroscopy,surgical findings,and histopathology of the Vickers ligament were evaluated.Results The 3D-CT revealed that the Vickers ligament originated in the metaphysis and formed a metaphyseal defect at the palmar ulnar radius.In the sequential MR coronal images,the Vickers ligament could be divided into 3 branches,extending to the lunate,triquetrum and ulnar styloid.Arthroscopy and surgical findings revealed that the nature of the Vickers ligament was the stretched palmar ligament of the wrist.The histopathology results revealed ligamentous tissue and fibrocartilaginous metaplasia with a structure similar to that of the triangular fibrocartilage complex(TFCC).Conclusions The Vickers ligament is not a separate aberrant ligament.The nature of the Vickers ligament is a combination of the stretched TFCC ligament(palmar radioulnar ligament,ulnotriquetral ligament and ulnolunate ligament)and radiolunate ligament.The possible pathogenesis of Madelung deformity might be focal early epiphyseal closure at the middle part of the sigmoid notch,which leads to focal growth retardation of the radius and pulls palmar ligaments proximally to form the Vickers ligament.

Brachioradialis tendon transfer and palmaris longus tendon graft for thumb avulsion:A case report and review of literature

BACKGROUND Thumb replantation following complete traumatic avulsion requires complex techniques to restore function,especially in cases of avulsion at the level of the metacarpophalangeal joint(MCP I)and avulsion of the flexor pollicis longus(FPL)at the musculotendinous junction.Possible treatments include direct tendon suture or tendon transfer,most commonly from the ring finger.To optimize function and avoid donor finger complications,we performed thumb replantation with flexion restoration using brachioradialis(BR)tendon transfer with palmaris longus(PL)tendon graft.CASE SUMMARY A 20-year-old left-handed male was admitted for a complete traumatic left thumb amputation following an accident while sliding from the top of a handrail.The patient presented with skin and bone avulsion at the MCP I,avulsion of the FPL tendon at the musculotendinous junction(zone 5),avulsion of the extensor pollicis longus tendon(zone T3),and avulsion of the thumb’s collateral arteries and nerves.The patient was treated with two stage thumb repair.The first intervention consisted of thumb replantation with MCP I arthrodesis,resection of avulsed FPL tendon and implantation of a silicone tendon prosthesis.The second intervention consisted of PL tendon graft and BR tendon transfer.Follow-up at 10 months showed good outcomes with active interphalangeal flexion of 70°,grip strength of 45 kg,key pinch strength of 15 kg and two-point discrimination threshold of 4 mm.CONCLUSION Flexion restoration after complete thumb amputation with FPL avulsion at the musculotendinous junction can be achieved using BR tendon transfer with PL tendon graft.

Inflammation and apoptosis accelerate progression to irreversible atrophy in denervated intrinsic muscles of the hand compared with biceps: proteomic analysis of a rat model of obstetric brachial plexus palsy

In treating patients with obstetric brachial plexus palsy,we noticed that denervated intrinsic muscles of the hand become irreversibly atrophic at a faster than denervated biceps.In a rat model of obstetric brachial plexus palsy,denervated intrinsic musculature of the forepaw entered the irreversible atrophy far earlier than denervated biceps.In this study,isobaric tags for relative and absolute quantitation were examined in the intrinsic musculature of forepaw and biceps on denervated and normal sides at 3 and 5 weeks to identify dysregulated proteins.Enrichment of pathways mapped by those proteins was analyzed by Kyoto Encyclopedia of Genes and Genomes analysis.At 3 weeks,119 dysregulated proteins in denervated intrinsic musculature of the forepaw were mapped to nine pathways for muscle regulation,while 67 dysregulated proteins were mapped to three such pathways at 5 weeks.At 3 weeks,27 upregulated proteins were mapped to five pathways involving inflammation and apoptosis,while two upregulated proteins were mapped to one such pathway at 5 weeks.At 3 and 5 weeks,53 proteins from pathways involving regrowth and differentiation were downregulated.At 3 weeks,64 dysregulated proteins in denervated biceps were mapped to five pathways involving muscle regulation,while,five dysregulated proteins were mapped to three such pathways at 5 weeks.One protein mapped to inflammation and apoptotic pathways was upregulated from one pathway at 3 weeks,while three proteins were downregulated from two other pathways at 5 weeks.Four proteins mapped to regrowth and differentiation pathways were upregulated from three pathways at 3 weeks,while two proteins were downregulated in another pathway at 5 weeks.These results implicated inflammation and apoptosis as critical factors aggravating atrophy of denervated intrinsic muscles of the hand during obstetric brachial plexus palsy.All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Fudan University,China(approval No.DF-325)in January 2015.

Supplementary motor area deactivation impacts the recovery of hand function from severe peripheral nerve injury

Although some patients have successful peripheral nerve regeneration,a poor recovery of hand function often occurs after peripheral nerve injury.It is believed that the capability of brain plasticity is crucial for the recovery of hand function.The supplementary motor area may play a key role in brain remodeling after peripheral nerve injury.In this study,we explored the activation mode of the supplementary motor area during a motor imagery task.We investigated the plasticity of the central nervous system after brachial plexus injury,using the motor imagery task.Results from functional magnetic resonance imaging showed that after brachial plexus injury,the motor imagery task for the affected limbs of the patients triggered no obvious activation of bilateral supplementary motor areas.This result indicates that it is difficult to excite the supplementary motor areas of brachial plexus injury patients during a motor imagery task,thereby impacting brain remodeling.Deactivation of the supplementary motor area is likely to be a serious problem for brachial plexus injury patients in terms of preparing,initiating and executing certain movements,which may be partly responsible for the unsatisfactory clinical recovery of hand function.

Synergistic effects of compound physical factor treatment on neurological outcome after peripheral nerve entrapment surgery A randomized controlled study

BACKGROUND： Iatrophysics can improve the velocity of local microcirculation at peripheral nerve injured sites and promote the recovery from injury. Research has shown that simultaneous application of two physical factors has synergistic effects on the recovery of peripheral nerve function. OBJECTIVE： To treat patients that received peripheral nerve entrapment surgery with comprehensive rehabilitation by decimeter wave therapy and electrical stimulation, and to observe the clinical effects of promoting nerve function recovery. DESIGN： Randomized controlled study. SETTINGS： Department of Orthopaedics, the Third Hospital of Baoding; Department of Hand Surgery, the Third Hospital of Hebei Medical University; Woman-Children Healthcare Center, Southern District, Baoding. PARTICIPANTS： A total of 124 patients, who received peripheral nerve entrapment surgery, were selected from the Department of Orthopaedics, the Third Hospital of Baoding between July 2001 and May 2007. All patients met the diagnostic standard of peripheral nerve entrapment syndrome defined by Doctor Chen in 1995. All subjects gave informed consent for treatments and conditions involved. The experiment was approved by a local ethics committee. All patients were randomly divided into four groups： electrical stimulation group, decimeter wave group, compound physical factor group, and control group, with 31 subjects in each group. METHODS： Patients received neurolysis at an appropriate interval after hospitalization. （1） Multi-form wave therapeutic equipment made in China was used to treat patients in the electrical stimulation group after neurolysis. Wave form, stimulus width, interval time, and stimulus intensity were regulated based on the grade of nerve injury. The details were as follows： mild nerve injury： 50-100-ms stimulus width and 1 500-2 000-ms intervals; moderate nerve injury： 100-200-ms stimulus width and 3 000-4 000-ms intervals; severe nerve injury： 200-300-ms stimulus width and 3 000--6 000-ms intervals. Current dosage was 20- 40 mA. The electrical stimulation was given 6 minutes/session, once a day, and 20 days were regarded as one treatment cycle. （2） A TMA-A double-frequent mild-hot therapeutic instrument was used on patients in the decimeter wave group after neurolysis. The therapeutic program was adapted to the early and middle-late phase. In the early phase, the decimeter wave was 10-15 W, 10 minutes/session, once a day; in the middle-late phase, the decimeter wave was 10-30 W, 20 minutes/session, once a day. Twenty days were regarded as one treatment cycle. （3） Patients in the compound physical factor group following neurolysis were treated the same as the decimeter wave group and electrical stimulation group, respectively. The treatment was performed once a day, and 20 days were regarded as one course. （4） Patients in the control group were not administered any physical treatment. MAIN OUTCOME MEASURES： Therapeutic efficacy was comprehensively evaluated based on motor and sensory evaluation criteria （set by Subassociation of Hand Surgery, Chinese Medical Association） at 1, 2, and 3 months after surgery, as well as changes in the electromyogram before and after operation. RESULTS： All 124 patients with peripheral nerve entrapment syndrome were included in the final analysis. One month after surgery, fineness rates in the electrical stimulation group, decimeter wave group, and compound physical factor group were not significantly different from those in the control group （P 〉 0.05）. There was also no significant difference between the electrical stimulation group, decimeter wave group, and compound physical factor group （P 〉 0.05）. Two months after surgery, fineness rates in the electrical stimulation group and decimeter wave group were not significantly different from the control group （P 〉 0.05）. However, fineness rates were higher in the compound physical factor group compared to the other three groups （P 〈 0.05）. There was no significant difference between the electrical stimulation group and the decimeter wave group （P 〉 0.05）. Three months after operation, fineness rates in the electrical stimulation group, decimeter wave group, and compound physical factor group were higher than the control group （P 〈 0.05）. However, there was no significant difference between the electrical stimulation group, decimeter wave group, and compound physical factor group （P 〉 0.05）. CONCLUSION： The combination of decimeter wave therapy and electrical stimulation can remarkably shorten the recovery time of peripheral nerve function. The synergistic effect is superior to that of electrical stimulation and decimeter wave alone. This suggests that those two physical factors have synergistic effects on the treatment of peripheral nerve entrapment syndrome.

Methods,Mechanisms,and Application Prospects for Enhancing Extracellular Vesicle Uptake

Extracellular vesicles(EVs)are considered to be a new generation of bioinspired nanoscale drug delivery systems due to their low immunogenicity,natural functionality,and excellent biocompatibility.However,limitations such as low uptake efficiency,insufficient production,and inhomogeneous performance undermine their potential.To address these issues,numerous researchers have put forward various methods and applications for enhancing EV uptake in recent decades.In this review,we introduce various methods for the cellular uptake of EVs and summarize recent advances on the methods and mechanisms for enhancing EV uptake.In addition,we provide further understanding regarding enhancing EV uptake and put forward prospects and challenges for the development of EV-based therapy in the future.

Modified contralateral C7 nerve transfer: the possibility of permitting ulnar nerve recovery is confirmed by 10 cases of autopsy

Contralateral C7 nerve transfer surgery is one of the most important surgical techniques for treating total brachial plexus nerve injury. In the traditional contralateral C7 nerve transfer surgery, the whole ulnar nerve on the paralyzed side is harvested for transfer, which completely sacrifices its potential of recovery. In the present, novel study, we report on the anatomical feasibility of a modified contralateral C7 nerve transfer surgery. Ten fresh cadavers (4 males and 6 females) provided by the Department of Anatomy, Histology, and Embryology at the Medical College of Fudan University, China were used in modified contralateral C7 nerve transfer surgery. In this surgical model, only the dorsal and superficial branches of the ulnar nerve and the medial antebrachial cutaneous nerve on the paralyzed side (left) were harvested for grafting the contralateral (right) C7 nerve and the recipient nerves. Both the median nerve and deep branch of the ulnar nerve on the paralyzed (left) side were recipient nerves. To verify the feasibility of this surgery, the distances between each pair of coaptating nerve ends were measured by a vernier caliper. The results validated that starting point of the deep branch of ulnar nerve and the starting point of the medial antebrachial cutaneous nerve at the elbow were close to each other and could be readily anastomosed. We investigated whether the fiber number of donor and recipient nerves matched one another. The axons were counted in sections of nerve segments distal and proximal to the coaptation sites after silver impregnation. Averaged axon number of the ulnar nerve at the upper arm level was approximately equal to the sum of the median nerve and proximal end of medial antebrachial cutaneous nerve (left: 0.94:1;right: 0.93:1). In conclusion, the contralateral C7 nerve could be transferred to the median nerve but also to the deep branch of the ulnar nerve via grafts of the ulnar nerve without deep branch and the medial antebrachial cutaneous nerve. The advantage over traditional surgery was that the recovery potential of the deep branch of ulnar nerve was preserved. The study was approved by the Ethics Committee of Fudan University (approval number: 2015-064) in July, 2015.

Characteristics and advantages of adeno-associated virus vector-mediated gene therapy for neurodegenerative diseases

Common neurodegenerative diseases of the central nervous system are characterized by progressive damage to the function of neurons, even leading to the permanent loss of function. Gene therapy via gene replacement or gene correction provides the potential for transformative therapies to delay or possibly stop further progression of the neurodegenerative disease in affected patients. Adeno-associated virus has been the vector of choice in recent clinical trials of therapies for neurodegenerative diseases due to its safety and efficiency in mediating gene transfer to the central nervous system. This review aims to discuss and summarize the progress and clinical applications of adeno-associated virus in neurodegenerative disease in central nervous system. Results from some clinical trials and successful cases of central neurodegenerative diseases deserve further study and exploration.

Small-worldness of brain networks after brachial plexus injury: a resting-state functional magnetic resonance imaging study

Research on brain function after brachial plexus injury focuses on local cortical functional reorganization,and few studies have focused on brain networks after brachial plexus injury.Changes in brain networks may help understanding of brain plasticity at the global level.We hypothesized that topology of the global cerebral resting-state functional network changes after unilateral brachial plexus injury.Thus,in this cross-sectional study,we recruited eight male patients with unilateral brachial plexus injury（right handedness,mean age of 27.9±5.4years old）and eight male healthy controls（right handedness,mean age of 28.6±3.2）.After acquiring and preprocessing resting-state magnetic resonance imaging data,the cerebrum was divided into 90 regions and Pearson’s correlation coefficient calculated between regions.These correlation matrices were then converted into a binary matrix with affixed sparsity values of 0.1–0.46.Under sparsity conditions,both groups satisfied this small-world property.The clustering coefficient was markedly lower,while average shortest path remarkably higher in patients compared with healthy controls.These findings confirm that cerebral functional networks in patients still show smallworld characteristics,which are highly effective in information transmission in the brain,as well as normal controls.Alternatively,varied small-worldness suggests that capacity of information transmission and integration in different brain regions in brachial plexus injury patients is damaged.

Establishing a rat model of spastic cerebral palsy by targeted ethanol injection

Spastic cerebral palsy is generally considered to result from cerebral cortical or pyramidal tract damage. Here, we precisely targeted the left pyramidal tract of 2-month-old Sprague-Dawley rats placed on a stereotaxic instrument under intraperitoneal anesthesia. Based on the rat brain stereotaxic map, a 1-mm hole was made 10 mm posterior to bregma and 0.8 mm left of sagittal suture. A microsyringe was inserted perpendicularly to the surface of the brain to a depth of 9.7 mm, and 15 wL of ethanol was slowly injected to establish a rat model of spastic cerebral palsy. After modeling, the rats appeared to have necrotic voids in the pyramidal tract and exhibited typical signs and symptoms of flexion spasms that lasted for a long period of time. These findings indicate that this is an effective and easy method of establishing a rat model of spastic cerebral palsy with good reproducibility. Ethanol as a chemical ablation agent specifically and thoroughly damages the py- ramidal tract, and therefore, the animals display flexion spasms, which are a typical symptom of the disease.

Interaction between Schwann cells and other cells during repair of peripheral nerve injury

Peripheral nerve injury(PNI)is common and,unlike damage to the central nervous system injured nerves can effectively regenerate depending on the location and severity of injury.Peripheral myelinating glia,Schwann cells(SCs),interact with various cells in and around the injury site and are important for debris elimination,repair,and nerve regeneration.Following PNI,Wallerian degeneration of the distal stump is rapidly initiated by degeneration of damaged axons followed by morphologic changes in SCs and the recruitment of circulating macrophages.Interaction with fibroblasts from the injured nerve microenvironment also plays a role in nerve repair.The replication and migration of injury-induced dedifferentiated SCs are also important in repairing the nerve.In particular,SC migration stimulates axonal regeneration and subsequent myelination of regenerated nerve fibers.This mobility increases SC interactions with other cells in the nerve and the exogenous environment,which influence SC behavior post-injury.Following PNI,SCs directly and indirectly interact with other SCs,fibroblasts,and macrophages.In addition,the inter-and intracellular mechanisms that underlie morphological and functional changes in SCs following PNI still require further research to explain known phenomena and less understood cell-specific roles in the repair of the injured peripheral nerve.This review provides a basic assessment of SC function post-PNI,as well as a more comprehensive evaluation of the literature concerning the SC interactions with macrophages and fibroblasts that can influence SC behavior and,ultimately,repair of the injured nerve.

Patterns of cortical reorganization in facial synkinesis:a task functional magnetic resonance imaging study

Facial synkinesis,a sequela of peripheral facial nerve palsy,is characterized by simultaneous involuntary facial movement during a voluntary desired one.Maladaptive cortical plasticity might be involved in the dysfunction of facial muscles.This cohort study investigated the cortical functional alterations in patients with unilateral facial synkinesis,using the task functional magnetic resonance imaging.Facial motor tasks,including blinking and smiling,were performed by 16 patients（aged 30.6 ± 4.5 years,14 females/2 males） and 24 age-and sex-matched healthy controls（aged 29.1 ± 4.2 years,19 females/5 males）.Results demonstrated that activation in the cortico-facial motor representation area was lower during tasks in patients with facial synkinesis compared with healthy controls.Facial movements on either side performed by patients caused more intensive activation of the supplementary motor area on the contralateral side of the affected face,than those on the unaffected side.Our results revealed that there was cortical reorganization in the primary sensorimotor area and the supplementary motor area.This study was registered in Chinese Clinical Trial Registry（registration number： Chi CTR1800014630）.

Biological characteristics of dynamic expression of nerve regeneration related growth factors in dorsal root ganglia after peripheral nerve injury

The regenerative capacity of peripheral nerves is limited after nerve injury.A number of growth factors modulate many cellular behaviors,such as proliferation and migration,and may contribute to nerve repair and regeneration.Our previous study observed the dynamic changes of genes in L4–6 dorsal root ganglion after rat sciatic nerve crush using transcriptome sequencing.Our current study focused on upstream growth factors and found that a total of 19 upstream growth factors were dysregulated in dorsal root ganglions at 3,9 hours,1,4,or 7 days after nerve crush,compared with the 0 hour control.Thirty-six rat models of sciatic nerve crush injury were prepared as described previously.Then,they were divided into six groups to measure the expression changes of representative genes at 0,3,9 hours,1,4 or 7 days post crush.Our current study measured the expression levels of representative upstream growth factors,including nerve growth factor,brain-derived neurotrophic factor,fibroblast growth factor 2 and amphiregulin genes,and explored critical signaling pathways and biological process through bioinformatic analysis.Our data revealed that many of these dysregulated upstream growth factors,including nerve growth factor,brain-derived neurotrophic factor,fibroblast growth factor 2 and amphiregulin,participated in tissue remodeling and axon growth-related biological processes Therefore,the experiment described the expression pattern of upstream growth factors in the dorsal root ganglia after peripheral nerve injury.Bioinformatic analysis revealed growth factors that may promote repair and regeneration of damaged peripheral nerves.All animal surgery procedures were performed in accordance with Institutional Animal Care Guidelines of Nantong University and ethically approved by the Administration Committee of Experimental Animals,China(approval No.20170302-017)on March 2,2017.

Use of nerve elongator to repair short-distance peripheral nerve defects: a prospective randomized study

Repair techniques for short-distance peripheral nerve defects, including adjacent joint flexion to reduce the distance between the nerve stump defects, ＂nerve splint＂ suturing, and nerve sle eve connection, have some disadvantages. Therefore, we designed a repair technique involving intraoperative tension-free application of a nerve elongator and obtained good outcomes in the repair of short-distance peripheral nerve defects in a previous animal study. The present study compared the clinical outcomes between the use of this nerve elongator and performance of the conventional method in the repair of short-distance transection injuries in human elbows. The 3-, 6-, and 12-month postoperative follow-up results demonstrated that early neurological function recovery was better in the nerve elongation group than in the conventional group, but no signif- icant difference in long-term neurological function recovery was detected between the two gro ups. In the nerve elongation group, the nerves were sutured without tension, and the duration of postoperative immobilization of the elbow was decreased. Elbow function rehabilitation was significantly better in the nerve elongation group than in the control group. Moreover, there were no security risks. The results of this study confirm that the use of this nerve elongator for repair of short-distance peripheral nerve defects is safe and effective.

Ca^(2＋) involvement in activation of extracellular-signal- regulated-kinase 1/2 and m-calpain after axotomy of the sciatic nerve

Detailed mechanisms behind regeneration after nerve injury, in particular signal transduction and the fate of Schwann cells （SCs）, are poorly understood. Here, we investigated axotomy-induced activation of extracellular- signal-regulated kinase-1/2 （ERK1/2; important for proliferation） and m-calpain in vitro, and the relation to Ca2＋ deletion and Schwann cell proliferation and death after rat sciatic nerve axotomy. Nerve segments were cultured for up to 72 hours with and without ethylene glycol-bis（β-aminoethyl ether）- N,N,N＇,N＇-tetraacetic acid （EGTA）. In some experiments, 5-bromo-2′-deoxyuridine （BrdU） was added during the last 24 hours to detect proliferating cells and propidium iodide （PI） was added at the last hour to detect dead and/or dying cells. Immunohistochemistry of sections of the cultured nerve segments was performed to label m-calpain and the phosphorylated and activated form of ERK1/2. The experiments revealed that immunoreactivity for p-ERK1/2 increased with time in organotypically cultured SCs. p-ERK1/2 and m-calpain were also observed in axons. A significant increase in the number of dead or dying SCs was observed in nerve segments cultured for 24 hours. When deprived of Ca2＋, activation of axonal m-calpain was reduced, whereas p-ERK1/2 was increased in SCs. Ca2＋ deprivation also significantly reduced the number of proliferating SCs, and instead increased the number of dead or dying SCs. Ca2＋ seems to play an important role in activation of ERK1/2 in SCs and in SC survival and proliferation. In addition, extracellular Ca2＋ levels are also required for m-calpain activation and up-regulation in axons. Thus, regulation of Ca2＋ levels is likely to be a useful method to promote SC proliferation.

Safety and efficacy of a nerve matrix membrane as a collagen nerve wrapping: a randomized, single-blind, multicenter clinical trial

A new nerve matrix membrane derived from decellularized porcine nerves has been shown to retain the major extracellular matrix components, and to be effective in preventing adhesion between the nerve anastomosis sites and the surrounding tissues in a rat sciatic nerve transection model, thereby enhancing regeneration of the nerve. The effectiveness of the membrane may be attributed to its various bioactive components. In this prospective, randomized, single-blind, parallel-controlled multicenter clinical trial, we compared the safety and efficacy of the new nerve matrix membrane with a previously approved bovine tendon-derived type I collagen nerve wrapping. A total of 120 patients with peripheral nerve injury were recruited from Beijing Jishuitan Hospital, The First Bethune Hospital of Jilin University, and Yantai Yuhuangding Hospital, China. The patients were randomly assigned to undergo end-to-end and tension-free neurorrhaphy with nerve matrix membrane(n = 60, 52 male, 8 female, mean age 41.34 years, experimental group) or tendon-derived collagen nerve wrapping(n = 60, 42 male, 18 female, mean age 40.17 years, control group). Patients were followed-up at 14 ± 5, 30 ± 7, 90 ± 10 and 180 ± 20 days after the operation. Safety evaluation included analyses of local and systemic reactions, related laboratory tests, and adverse reactions. Efficacy evaluation included a static 2-point discrimination test, a moving 2-point discrimination test, and a Semmes–Weinstein monofilament examination. Sensory nerve function was evaluated with the British Medical Research Council Scale and Semmes–Weinstein monofilament examination. The ratio(percentage) of patients with excellent to good results in sensory nerve recovery 180 ± 20 days after the treatment was used as the primary effectiveness index. The percentages of patients with excellent to good results in the experimental and control groups were 98.00% and 94.44%, respectively, with no significant difference between the two groups. There were no significant differences in the results of routine blood tests, liver and renal function tests, coagulation function tests, or immunoglobulin tests at 14 and 180 days postoperatively between the two groups. These findings suggest that the novel nerve matrix membrane is similar in efficacy to the commercially-available bovine-derived collagen membrane in the repair of peripheral nerve injury, and it may therefore serve as an alternative in the clinical setting. The clinical trial was approved by the Institutional Ethics Committee of Beijing Jishuitan Hospital, China(approval No. 20160902) on October 8, 2016, the Institutional Ethics Committee of the First Bethune Hospital of Jilin University, China(approval No. 160518-088) on December 14, 2016, and the Institutional Ethics Committee of Yantai Yuhuangding Hospital, China(approval No. 2016-10-01) on December 9, 2016. The clinical trial was registered with the Chinese Clinical Trial Registry(registration number: Chi CTR2000033324) on May 28, 2020.