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 pron...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.展开更多
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 th...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.展开更多
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 p...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.展开更多
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...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.展开更多
Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities.Research on the pathogenesis of peripheral nerve injury has focused on pathological changes...Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities.Research on the pathogenesis of peripheral nerve injury has focused on pathological changes at individual injury sites,neglecting multilevel pathological analysis of the overall nervous system and target organs.This has led to restrictions on current therapeutic approaches.In this paper,we first summarize the potential mechanisms of peripheral nerve injury from a holistic perspective,covering the central nervous system,peripheral nervous system,and target organs.After peripheral nerve injury,the cortical plasticity of the brain is altered due to damage to and regeneration of peripheral nerves;changes such as neuronal apoptosis and axonal demyelination occur in the spinal cord.The nerve will undergo axonal regeneration,activation of Schwann cells,inflammatory response,and vascular system regeneration at the injury site.Corresponding damage to target organs can occur,including skeletal muscle atrophy and sensory receptor disruption.We then provide a brief review of the research advances in therapeutic approaches to peripheral nerve injury.The main current treatments are conducted passively and include physical factor rehabilitation,pharmacological treatments,cell-based therapies,and physical exercise.However,most treatments only partially address the problem and cannot complete the systematic recovery of the entire central nervous system-peripheral nervous system-target organ pathway.Therefore,we should further explore multilevel treatment options that produce effective,long-lasting results,perhaps requiring a combination of passive(traditional)and active(novel)treatment methods to stimulate rehabilitation at the central-peripheral-target organ levels to achieve better functional recovery.展开更多
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 r...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.展开更多
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 t...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.展开更多
BACKGROUND Postoperative anxiety,depression,irritability,and even fear in patients with intertrochanteric femoral fractures may hinder recovery,compromise treatment efficacy,and impede rehabilitation.AIM To investigat...BACKGROUND Postoperative anxiety,depression,irritability,and even fear in patients with intertrochanteric femoral fractures may hinder recovery,compromise treatment efficacy,and impede rehabilitation.AIM To investigate the correlations among anxiety,depression,sense of coherence(SOC),and post-traumatic growth(PTG)in patients who underwent intertrochanteric femoral fracture surgery to improve clinical management strategies and outcomes.METHODS This study carefully selected 211 patients who received surgical treatment for intertrochanteric femoral fractures and were admitted to Dongying People’s Hospital from March 2022 to March 2024.Anxiety and depression in these patients were assessed with the anxiety and depression subscales of the Hospital Anxiety and Depression Scale(HADS),respectively.SOC was evaluated using the 13-item SOC scale(SOC-13),which encompasses three key dimensions:Comprehensibility,manageability,and meaningfulness.PTG was assessed with the Chinese version of PTG Inventory(CPTGI),covering five distinct dimensions:Personal strength,appreciation of life,relating to others,new possibilities,and spiritual change.The Pearson correlation coefficient was used to meticulously analyze the associations among HADS-Anxiety,HADS-Depression,SOC-13,and CPTGI.Further,univariate and multivariate analyses were conducted to identify factors that affect PTG in patients who underwent intertrochanteric femoral fracture surgery.RESULTS The collected data demonstrated that 67.30%and 60.66%of the 211 patients experienced anxiety and depression,respectively,with overall anxiety levels ranging from mild to moderate and depression levels being mild.The mean SOC-13 score was 55.73±8.81 points,indicating a generally low SOC level.The average CPTGI score was 54.93±9.92 points,demonstrating a relatively low PTG level.Notably,both HADS-Anxiety and HADS-Depression scores were significantly negatively correlated with CPTGI,whereas SOC-13 scores were significantly positively correlated with CPTGI.Univariate and multivariate analyses identified the presence of comorbidities[odds ratio(OR)=2.747,P=0.003],monthly household income(OR=3.292,P<0.001),and exercise habits(OR=4.651,P<0.001)as independent predictors of PTG in patients.CONCLUSION The results of this study indicate a significant negative correlation of anxiety and depression with PTG in patients after intertrochanteric femoral fracture surgery,whereas a significant positive association exists between SOC and PTG.This study helps more comprehensively understand the psychological status and recovery processes of such patients,thereby potentially providing valuable information for clinical practice and psychological interventions.展开更多
The healing of diabetic wounds poses a significant healthcare burden due to persistent inflammation,M1 macrophage aggregation,and high glucose levels in the microenvironment.Previous studies have demonstrated that imm...The healing of diabetic wounds poses a significant healthcare burden due to persistent inflammation,M1 macrophage aggregation,and high glucose levels in the microenvironment.Previous studies have demonstrated that immunomodulatory hydrogel dressings can facilitate diabetic wound healing.However,current immunomodulatory hydrogels require costly and complex treatments such as cell therapy and cytokines.Herein,a hierarchical hydrogel dressing with continuous biochemical gradient based on glycyrrhizic acid(GA) was constructed to modulate immunomodulatory processes in diabetic wounds.The hydrogels present many desirable features,such as tunable mechanical properties,broad antibacterial ability,outstanding conductive,transparent,and self-adhesive properties.The resultant hydrogel can promote diabetic wound healing by preventing bacterial infection,promoting macrophage polarization,improving the inflammatory microenvironment,and inducing angiogenesis and neurogenesis.Furthermore,electrical stimulation(ES) can further promote the healing of chronic diabetic wounds,providing valuable guidance for relevant clinical practice.展开更多
Serotonin(5-hydroxytryptamine,5-HT),a neurotransmitter known for its roles in the central nervous system,showing dual effects in various pathological conditions,including tumor progression and wound healing.This revie...Serotonin(5-hydroxytryptamine,5-HT),a neurotransmitter known for its roles in the central nervous system,showing dual effects in various pathological conditions,including tumor progression and wound healing.This review explores the complex and context-dependent actions of 5-HT,highlighting its contrasting roles in promoting tumor growth and facilitating wound repair.5-HT can enhance tumor growth,survival,and metastasis via its receptors,but it also accelerates wound healing by stimulating cell proliferation,migration,and angiogenesis.This duality emphasizes the intricate balance of 5-HT and its receptors in the body.We discuss the synthesis,storage,secretion,and metabolism of 5-HT,as well as the classification and mechanisms of its receptors(5-HTRs)in different cell types under pathological conditions.We further examine the potential roles of 5-HT in both tumor progress and wound healing,proposing targeted strategies for each disease state.For tumors,“blocking therapy”involving receptor antagonists or gene silencing may inhibit tumor progression,while“activation therapy”can stimulate wound healing by enhancing receptor activation on skin cells.Challenges in clinical application,including issues related to targeting,specificity,and dosage,are addressed,alongside the promise of nanotechnology for improving targeted drug delivery.The review also explores emerging research on 5-HT's interaction with the immune system,offering insights into potential immunotherapeutic strategies for both cancer and wound healing.By balancing 5-HT's diverse effects,personalized treatments can be developed to optimize therapeutic outcomes in both contexts.展开更多
The surface physiochemical features of nanomedicine are essential for controlling biointerfacial interactions in biological compartments and achieving the programmed delivery scenario to intracellular targets.This wor...The surface physiochemical features of nanomedicine are essential for controlling biointerfacial interactions in biological compartments and achieving the programmed delivery scenario to intracellular targets.This work presents a novel dynamic triple-transformable surface engineering strategy that can adapt to sequential variable biological microenvironments and intelligently managing the previously acknowledged biological obstacles.By employing click chemistry,the surface of a classical PEGylated pDNA delivery nanoparticles were tethered with a multiple of charge-reversible polymers to endow the dynamic biointerfacial surroundings.Crucially,the dynamic surroundings had negative charge under physiological circumstances(pH 7.4),which inhibited structural disintegration brought on by charged biological species and anionic nuclease degradation.In addition,by regulating the first pass effect,the nanoparticles demonstrated appreciable stealth function that led to persistent systemic retention and improved bioavailability and consistent internalization into the targeted cells.In subsequence to cell endocytosis,translocation from the digestive endolysosomes to the targeted cytosol was facilitated due to acidification(endosomal pH 5.5)of the dynamic surroundings into highly positive charge,consequently leading to explosive disruptive effects on the endolysosomal structures and retrieve the bio-vulnerable pDNA payloads.In conclusion,our proposed unique dynamic surface chemistry provides a viable delivery mechanism that successfully navigates a series of biological roadblocks and collaborates to effectively express the encapsulated pDNA at the targeted cells.展开更多
Background:With advancements in burn treatment and intensive care leading to decreased mortality rates,a growing cohort of burn survivors is emerging.These individuals may be susceptible to frailty,characterized by re...Background:With advancements in burn treatment and intensive care leading to decreased mortality rates,a growing cohort of burn survivors is emerging.These individuals may be susceptible to frailty,characterized by reduced physiological reserve and increased vulnerability to stressors commonly associated with aging,which significantly complicates their recovery process.To date,no study has investigated burns as a potential risk factor for frailty.This study aimed to determine the short-term prevalence of frailty among burn survivors’months after injury and compare it with that of the general population.Methods:A post hoc analysis was conducted on the Randomized Trial of Enteral Glutamine to Minimize the Effects of Burn Injury(RE-ENERGIZE)trial,an international randomized-controlled trial involving 1200 burn injury patients with partial-or full-thickness burns.Participants who did not complete the 36-Item Short Form Health Survey(SF-36)questionnaire were excluded.Data for the general population were obtained from the 2022 National Health Interview Survey(NHIS).Frailty was assessed using the FRAIL(Fatigue,Resistance,Ambulation,Illness,Loss of weight)scale.Due to lack of data on loss of weight,for the purposes of this study,malnutrition was used as the fifth variable.Illness and malnutrition were based on admission data,while fatigue,resistance,and ambulation were determined from post-discharge responses to the SF-36.The burn cohort and general population groups were matched using propensity score matching and compared in terms of frailty status.Within the burn group,patients were divided into different subgroups based on their frailty status,and the differences in their(instrumental)activities of daily living(iADL and ADL)were compared.A multivariable analysis was performed within the burn cohort to identify factors predisposing to frailty as well as compromised iADL and ADL.Results:Out of the 1200 burn patients involved in the study,600 completed the required questionnaires[follow-up time:(5.5±2.3)months]and were matched to 1200 adults from the general population in the U.S.In comparison to the general population,burn patients exhibited a significantly higher likelihood of being pre-frail(42.3%vs.19.8%,P<0.0001),or frail(13.0%vs.1.0%,P<0.0001).When focusing on specific components,burn patients were more prone to experiencing fatigue(25.8%vs.13.5%,P<0.0001),limited resistance(34.0%vs.2.7%,P<0.0001),and restricted ambulation(41.8%vs.3.8%,P<0.0001).Conversely,the incidence rate of illness was observed to be higher in the general population(1.2%vs.2.8%,P=0.03),while no significant difference was detected regarding malnutrition(2.3%vs.2.6%,P=0.75).Furthermore,in comparison with robust burn patients,it was significantly more likely for pre-frail and frail patients to disclose compromise in ADL and iADL.The frail cohort reported the most pronounced limitation.Conclusions:Our findings suggest a higher incidence of post-discharge frailty among burn survivors in the short-term following injury.Burn survivors experience compromised fatigue,resistance,and ambulation,while rates of illness and malnutrition were lower or unchanged,respectively.These results underscore the critical need for early identification of frailty after a burn injury,with timely and comprehensive involvement of a multidisciplinary team including burn and pain specialists,community physicians,physiotherapists,nutritionists,and social workers.This collaborative effort can ensure holistic care to address and mitigate frailty in this patient population.展开更多
The increase in neurotrophic factors after craniocerebral injury has been shown to promote fracture healing. Moreover, neurotrophic factors play a key role in the regeneration and repair of peripheral nerve. However, ...The increase in neurotrophic factors after craniocerebral injury has been shown to promote fracture healing. Moreover, neurotrophic factors play a key role in the regeneration and repair of peripheral nerve. However, whether craniocerebral injury alters the repair of peripheral nerve injuries remains poorly understood. Rat injury models were established by transecting the left sciatic nerve and using a free-fall device to induce craniocerebral injury. Compared with sciat- ic nerve injury alone after 6-12 weeks, rats with combined sciatic and craniocerebral injuries showed decreased sciatic functional index, increased recovery of gastrocnemius muscle wet weight, recovery of sciatic nerve ganglia and corresponding spinal cord segment neuron mor- phologies, and increased numbers of horseradish peroxidase-labeled cells. These results indicate that craniocerebral injury promotes the repair of peripheral nerve injury.展开更多
In this study, we constructed tissue-engineered nerves with acellular nerve allografts in Sprague-Dawley rats, which were prepared using chemical detergents-enzymatic digestion and mechanical methods, in combination w...In this study, we constructed tissue-engineered nerves with acellular nerve allografts in Sprague-Dawley rats, which were prepared using chemical detergents-enzymatic digestion and mechanical methods, in combination with bone marrow mesenchymal stem cells of Wistar rats cultured in vitro, to repair 15 mm sciatic bone defects in Wistar rats. At postoperative 12 weeks, electrophysiological detection results showed that the conduction velocity of regenerated nerve after repair with tissue-engineered nerves was similar to that after autologous nerve grafting, and was higher than that after repair with acellular nerve allografts. Immunohistochemical staining revealed that motor endplates with acetylcholinesterase-positive nerve fibers were orderly arranged in the middle and superior parts of the gastrocnemius muscle; regenerated nerve tracts and sprouted branches were connected with motor endplates, as shown by acetylcholinesterase histochemistry combined with silver staining. The wet weight ratio of the tibialis anterior muscle at the affected contralateral hind limb was similar to the sciatic nerve after repair with autologous nerve grafts, and higher than that after repair with acellular nerve allografts. The hind limb motor function at the affected side was significantly improved, indicating that acellular nerve allografts combined with bone marrow mesenchymal stem cell bridging could promote functional recovery of rats with sciatic nerve defects.展开更多
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 stereotaxi...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.展开更多
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 hel...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.展开更多
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 ner...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.展开更多
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...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.展开更多
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 ...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.展开更多
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 cell...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.展开更多
基金Clinical Study of Artificial Dermis Combined with Skin Flap Replacement Flap in Limb Wound Repair,No.WX21C27.
文摘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.
基金supported by the Youth Researcher Foundation of Shanghai Health Development Planning Commission,No.20124319
文摘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.
基金supported by the National Natural Science Foundation of China,No.816019591003263(to JXW)the National Basic Research Program of China(973 Program),No.2014CB542203(to LC)
文摘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.
基金supported in part by NIH R01 NS100531,R01 NS103481NIH R21NS130241(to LD)+3 种基金Merit Review Award I01 BX002356,I01 BX003705 from the U.S.Department of Veterans AffairsIndiana Spinal Cord and Brain Injury Research Foundation(No.19919)Mari Hulman George Endowment Funds(to XMX)Indiana Spinal Cord&Brain Injury Research Fund from ISDH(to NKL and LD)。
文摘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.
基金supported by grants from the Natural Science Foundation of Tianjin(General Program),Nos.23JCYBJC01390(to RL),22JCYBJC00220(to XC),and 22JCYBJC00210(to QL).
文摘Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities.Research on the pathogenesis of peripheral nerve injury has focused on pathological changes at individual injury sites,neglecting multilevel pathological analysis of the overall nervous system and target organs.This has led to restrictions on current therapeutic approaches.In this paper,we first summarize the potential mechanisms of peripheral nerve injury from a holistic perspective,covering the central nervous system,peripheral nervous system,and target organs.After peripheral nerve injury,the cortical plasticity of the brain is altered due to damage to and regeneration of peripheral nerves;changes such as neuronal apoptosis and axonal demyelination occur in the spinal cord.The nerve will undergo axonal regeneration,activation of Schwann cells,inflammatory response,and vascular system regeneration at the injury site.Corresponding damage to target organs can occur,including skeletal muscle atrophy and sensory receptor disruption.We then provide a brief review of the research advances in therapeutic approaches to peripheral nerve injury.The main current treatments are conducted passively and include physical factor rehabilitation,pharmacological treatments,cell-based therapies,and physical exercise.However,most treatments only partially address the problem and cannot complete the systematic recovery of the entire central nervous system-peripheral nervous system-target organ pathway.Therefore,we should further explore multilevel treatment options that produce effective,long-lasting results,perhaps requiring a combination of passive(traditional)and active(novel)treatment methods to stimulate rehabilitation at the central-peripheral-target organ levels to achieve better functional recovery.
基金Supported by Special TCM Innovation Project of Hebei Provincial Department of Science and Technology,No.223777130DScientific Research Project of Hebei Province Administration of Traditional Chinese Medicine,No.2024215.
文摘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.
文摘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.
文摘BACKGROUND Postoperative anxiety,depression,irritability,and even fear in patients with intertrochanteric femoral fractures may hinder recovery,compromise treatment efficacy,and impede rehabilitation.AIM To investigate the correlations among anxiety,depression,sense of coherence(SOC),and post-traumatic growth(PTG)in patients who underwent intertrochanteric femoral fracture surgery to improve clinical management strategies and outcomes.METHODS This study carefully selected 211 patients who received surgical treatment for intertrochanteric femoral fractures and were admitted to Dongying People’s Hospital from March 2022 to March 2024.Anxiety and depression in these patients were assessed with the anxiety and depression subscales of the Hospital Anxiety and Depression Scale(HADS),respectively.SOC was evaluated using the 13-item SOC scale(SOC-13),which encompasses three key dimensions:Comprehensibility,manageability,and meaningfulness.PTG was assessed with the Chinese version of PTG Inventory(CPTGI),covering five distinct dimensions:Personal strength,appreciation of life,relating to others,new possibilities,and spiritual change.The Pearson correlation coefficient was used to meticulously analyze the associations among HADS-Anxiety,HADS-Depression,SOC-13,and CPTGI.Further,univariate and multivariate analyses were conducted to identify factors that affect PTG in patients who underwent intertrochanteric femoral fracture surgery.RESULTS The collected data demonstrated that 67.30%and 60.66%of the 211 patients experienced anxiety and depression,respectively,with overall anxiety levels ranging from mild to moderate and depression levels being mild.The mean SOC-13 score was 55.73±8.81 points,indicating a generally low SOC level.The average CPTGI score was 54.93±9.92 points,demonstrating a relatively low PTG level.Notably,both HADS-Anxiety and HADS-Depression scores were significantly negatively correlated with CPTGI,whereas SOC-13 scores were significantly positively correlated with CPTGI.Univariate and multivariate analyses identified the presence of comorbidities[odds ratio(OR)=2.747,P=0.003],monthly household income(OR=3.292,P<0.001),and exercise habits(OR=4.651,P<0.001)as independent predictors of PTG in patients.CONCLUSION The results of this study indicate a significant negative correlation of anxiety and depression with PTG in patients after intertrochanteric femoral fracture surgery,whereas a significant positive association exists between SOC and PTG.This study helps more comprehensively understand the psychological status and recovery processes of such patients,thereby potentially providing valuable information for clinical practice and psychological interventions.
基金supported by Natural Science Foundation of Jilin Province(No.SKL202302002)。
文摘The healing of diabetic wounds poses a significant healthcare burden due to persistent inflammation,M1 macrophage aggregation,and high glucose levels in the microenvironment.Previous studies have demonstrated that immunomodulatory hydrogel dressings can facilitate diabetic wound healing.However,current immunomodulatory hydrogels require costly and complex treatments such as cell therapy and cytokines.Herein,a hierarchical hydrogel dressing with continuous biochemical gradient based on glycyrrhizic acid(GA) was constructed to modulate immunomodulatory processes in diabetic wounds.The hydrogels present many desirable features,such as tunable mechanical properties,broad antibacterial ability,outstanding conductive,transparent,and self-adhesive properties.The resultant hydrogel can promote diabetic wound healing by preventing bacterial infection,promoting macrophage polarization,improving the inflammatory microenvironment,and inducing angiogenesis and neurogenesis.Furthermore,electrical stimulation(ES) can further promote the healing of chronic diabetic wounds,providing valuable guidance for relevant clinical practice.
基金supported by Research Foundation of Education Bureau of Hunan Province,China(No.23A0002)。
文摘Serotonin(5-hydroxytryptamine,5-HT),a neurotransmitter known for its roles in the central nervous system,showing dual effects in various pathological conditions,including tumor progression and wound healing.This review explores the complex and context-dependent actions of 5-HT,highlighting its contrasting roles in promoting tumor growth and facilitating wound repair.5-HT can enhance tumor growth,survival,and metastasis via its receptors,but it also accelerates wound healing by stimulating cell proliferation,migration,and angiogenesis.This duality emphasizes the intricate balance of 5-HT and its receptors in the body.We discuss the synthesis,storage,secretion,and metabolism of 5-HT,as well as the classification and mechanisms of its receptors(5-HTRs)in different cell types under pathological conditions.We further examine the potential roles of 5-HT in both tumor progress and wound healing,proposing targeted strategies for each disease state.For tumors,“blocking therapy”involving receptor antagonists or gene silencing may inhibit tumor progression,while“activation therapy”can stimulate wound healing by enhancing receptor activation on skin cells.Challenges in clinical application,including issues related to targeting,specificity,and dosage,are addressed,alongside the promise of nanotechnology for improving targeted drug delivery.The review also explores emerging research on 5-HT's interaction with the immune system,offering insights into potential immunotherapeutic strategies for both cancer and wound healing.By balancing 5-HT's diverse effects,personalized treatments can be developed to optimize therapeutic outcomes in both contexts.
基金financially supported by National Key Research and Development Program(No.2022YFD1700200)National Natural Science Foundation of China(No.32171330)Training Program of the National Natural Science Foundation of China(Nos.2021-ZLLH-14,2021-ZLLH-05)。
文摘The surface physiochemical features of nanomedicine are essential for controlling biointerfacial interactions in biological compartments and achieving the programmed delivery scenario to intracellular targets.This work presents a novel dynamic triple-transformable surface engineering strategy that can adapt to sequential variable biological microenvironments and intelligently managing the previously acknowledged biological obstacles.By employing click chemistry,the surface of a classical PEGylated pDNA delivery nanoparticles were tethered with a multiple of charge-reversible polymers to endow the dynamic biointerfacial surroundings.Crucially,the dynamic surroundings had negative charge under physiological circumstances(pH 7.4),which inhibited structural disintegration brought on by charged biological species and anionic nuclease degradation.In addition,by regulating the first pass effect,the nanoparticles demonstrated appreciable stealth function that led to persistent systemic retention and improved bioavailability and consistent internalization into the targeted cells.In subsequence to cell endocytosis,translocation from the digestive endolysosomes to the targeted cytosol was facilitated due to acidification(endosomal pH 5.5)of the dynamic surroundings into highly positive charge,consequently leading to explosive disruptive effects on the endolysosomal structures and retrieve the bio-vulnerable pDNA payloads.In conclusion,our proposed unique dynamic surface chemistry provides a viable delivery mechanism that successfully navigates a series of biological roadblocks and collaborates to effectively express the encapsulated pDNA at the targeted cells.
基金supported by the U.S.Department of Defense(W81XWH-09-2-0194 for the pilot phase)the Canadian Institutes of Health Research(MCT-94834 for the pilot phase and 14238 for the definitive phase).
文摘Background:With advancements in burn treatment and intensive care leading to decreased mortality rates,a growing cohort of burn survivors is emerging.These individuals may be susceptible to frailty,characterized by reduced physiological reserve and increased vulnerability to stressors commonly associated with aging,which significantly complicates their recovery process.To date,no study has investigated burns as a potential risk factor for frailty.This study aimed to determine the short-term prevalence of frailty among burn survivors’months after injury and compare it with that of the general population.Methods:A post hoc analysis was conducted on the Randomized Trial of Enteral Glutamine to Minimize the Effects of Burn Injury(RE-ENERGIZE)trial,an international randomized-controlled trial involving 1200 burn injury patients with partial-or full-thickness burns.Participants who did not complete the 36-Item Short Form Health Survey(SF-36)questionnaire were excluded.Data for the general population were obtained from the 2022 National Health Interview Survey(NHIS).Frailty was assessed using the FRAIL(Fatigue,Resistance,Ambulation,Illness,Loss of weight)scale.Due to lack of data on loss of weight,for the purposes of this study,malnutrition was used as the fifth variable.Illness and malnutrition were based on admission data,while fatigue,resistance,and ambulation were determined from post-discharge responses to the SF-36.The burn cohort and general population groups were matched using propensity score matching and compared in terms of frailty status.Within the burn group,patients were divided into different subgroups based on their frailty status,and the differences in their(instrumental)activities of daily living(iADL and ADL)were compared.A multivariable analysis was performed within the burn cohort to identify factors predisposing to frailty as well as compromised iADL and ADL.Results:Out of the 1200 burn patients involved in the study,600 completed the required questionnaires[follow-up time:(5.5±2.3)months]and were matched to 1200 adults from the general population in the U.S.In comparison to the general population,burn patients exhibited a significantly higher likelihood of being pre-frail(42.3%vs.19.8%,P<0.0001),or frail(13.0%vs.1.0%,P<0.0001).When focusing on specific components,burn patients were more prone to experiencing fatigue(25.8%vs.13.5%,P<0.0001),limited resistance(34.0%vs.2.7%,P<0.0001),and restricted ambulation(41.8%vs.3.8%,P<0.0001).Conversely,the incidence rate of illness was observed to be higher in the general population(1.2%vs.2.8%,P=0.03),while no significant difference was detected regarding malnutrition(2.3%vs.2.6%,P=0.75).Furthermore,in comparison with robust burn patients,it was significantly more likely for pre-frail and frail patients to disclose compromise in ADL and iADL.The frail cohort reported the most pronounced limitation.Conclusions:Our findings suggest a higher incidence of post-discharge frailty among burn survivors in the short-term following injury.Burn survivors experience compromised fatigue,resistance,and ambulation,while rates of illness and malnutrition were lower or unchanged,respectively.These results underscore the critical need for early identification of frailty after a burn injury,with timely and comprehensive involvement of a multidisciplinary team including burn and pain specialists,community physicians,physiotherapists,nutritionists,and social workers.This collaborative effort can ensure holistic care to address and mitigate frailty in this patient population.
基金supported by a grant from Hebei Provincial Science and Technology Department in China,No.142777105D,13277772D
文摘The increase in neurotrophic factors after craniocerebral injury has been shown to promote fracture healing. Moreover, neurotrophic factors play a key role in the regeneration and repair of peripheral nerve. However, whether craniocerebral injury alters the repair of peripheral nerve injuries remains poorly understood. Rat injury models were established by transecting the left sciatic nerve and using a free-fall device to induce craniocerebral injury. Compared with sciat- ic nerve injury alone after 6-12 weeks, rats with combined sciatic and craniocerebral injuries showed decreased sciatic functional index, increased recovery of gastrocnemius muscle wet weight, recovery of sciatic nerve ganglia and corresponding spinal cord segment neuron mor- phologies, and increased numbers of horseradish peroxidase-labeled cells. These results indicate that craniocerebral injury promotes the repair of peripheral nerve injury.
基金financially sponsored by the Natural Science Foundation of Liaoning Province,No.201102135
文摘In this study, we constructed tissue-engineered nerves with acellular nerve allografts in Sprague-Dawley rats, which were prepared using chemical detergents-enzymatic digestion and mechanical methods, in combination with bone marrow mesenchymal stem cells of Wistar rats cultured in vitro, to repair 15 mm sciatic bone defects in Wistar rats. At postoperative 12 weeks, electrophysiological detection results showed that the conduction velocity of regenerated nerve after repair with tissue-engineered nerves was similar to that after autologous nerve grafting, and was higher than that after repair with acellular nerve allografts. Immunohistochemical staining revealed that motor endplates with acetylcholinesterase-positive nerve fibers were orderly arranged in the middle and superior parts of the gastrocnemius muscle; regenerated nerve tracts and sprouted branches were connected with motor endplates, as shown by acetylcholinesterase histochemistry combined with silver staining. The wet weight ratio of the tibialis anterior muscle at the affected contralateral hind limb was similar to the sciatic nerve after repair with autologous nerve grafts, and higher than that after repair with acellular nerve allografts. The hind limb motor function at the affected side was significantly improved, indicating that acellular nerve allografts combined with bone marrow mesenchymal stem cell bridging could promote functional recovery of rats with sciatic nerve defects.
文摘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.
文摘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.
基金supported by the National Natural Science Foundation of China,No.81572127(to JL)
文摘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.
基金supported by the Wu Jieping Medical Foundation of China,No. 320.6750.17273 (to YBG)。
文摘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.
文摘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.
基金This work was also supported by the National Natural Science Foundation of China,No.81901365(to WRQ)Jilin Science and Technology Agency Funds in China,Nos.20180101118JC(to RL),20180520115JH(to BPC)and 20190103076JH(to WRQ).
文摘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.
