Background:Rats are often used to prepare skin defect models.However,the skin defect sizes of the models prepared by researchers are different,and the lack of consensus on the critical-size defect makes it difficult t...Background:Rats are often used to prepare skin defect models.However,the skin defect sizes of the models prepared by researchers are different,and the lack of consensus on the critical-size defect makes it difficult to compare their research results.Methods:The time for wound closure was evaluated and recorded through gross observation.The regression equation between the healing time and the diameter of skin defect was established,which can be used to predict the healing time for a certain skin defect size in rats.Histochemical and immunohistochemical staining was used to observe the regeneration and reconstruction of skin appendages,and the functional skin repair was quantitatively scored.Results:The critical-size defect of rats was determined based on the maximum capacity of structural skin repair,and the functional skin repair was quantitatively scored based on the regeneration and reconstruction of skin appendages.The allowable range of critical-size skin defect of SD rats lies between 45 and 50 mm in diameter.The concept of structural repair and the category of functional repair of injured skin are put forward.The regression equation between the structural skin healing time and defect diameters is established.Conclusion:The allowable range of skin critical-size defect of SD rats lies between 45 and 50 mm in diameter.The regression equation between the structural skin healing time and defect diameters can be used to predict the healing time for a certain skin defect size in rats.展开更多
In ultraviolet cured-in-place-pipe(UV-CIPP)pipeline rehabilitation,resin performance critically determines repair effectiveness.Current UV-curable resins exhibit high volatile organic compound(VOC)emissions and inadeq...In ultraviolet cured-in-place-pipe(UV-CIPP)pipeline rehabilitation,resin performance critically determines repair effectiveness.Current UV-curable resins exhibit high volatile organic compound(VOC)emissions and inadequate post-cure toughness,which compromise fatigue resistance during service.To address these issues,we synthesized hydroxyl-terminated polyurethane acrylate prepolymers using diphenylmethane diisocyanate(MDI),polypropylene glycol(PPG),and hydroxyethyl methacrylate(HEMA).Fourier transform infrared spectroscopy(FTIR)confirmed successful prepolymer synthesis.We developed UV-curable resins by incorporating various crosslinking monomers and optimized the formulations through mechanical property analysis.Testing revealed that the polyurethane-acrylic UV-cured resin system combines polyurethane's mechanical excellence with acrylics'high UV-curing activity.The PPG200/MDI/HEMA formulation achieved superior performance,with a tensile strength of 55.31 MPa,an impact toughness of 22.7 kJ/m^(2),and a heat deflection temperature(HDT)of 132℃.The optimized system eliminates volatile components while maintaining high reactivity,addressing critical limitations in trenchless pipeline rehabilitation.The improved mechanical properties meet the operational demands of underground pipes,suggesting practical applicability in trenchless pipeline repair.展开更多
The increasing occurrence of corrosion-related damage in steel pipelines has led to the growing use of composite-based repair techniques as an efficient alternative to traditional replacement methods.Computer modeling...The increasing occurrence of corrosion-related damage in steel pipelines has led to the growing use of composite-based repair techniques as an efficient alternative to traditional replacement methods.Computer modeling and structural analysis were performed for the repair reinforcement of a steel pipeline with a composite bandage.A preliminary analysis of possible contact interaction schemes was implemented based on the theory of cylindrical shells,taking into account transverse shear deformations.The finite element method was used for a detailed study of the stress state of the composite bandage and the reinforced section of the pipeline.The limit state of the reinforced section was assessed based on the von Mises criterion for steel and the Tsai-Wu criterion for composites.The effectiveness of the repair was demonstrated on a pipeline whose wall thickness had decreased by 20%as a result of corrosion damage.At a nominal pressure of P=6 MPa,the maximum normal stress in the weakened area reached 381 MPa.The installation of a composite bandage reduced this stress to 312 MPa,making the repaired section virtually as strong as the undamaged pipeline.Due to the linearity of the problem,the results obtained can be easily used to find critical internal pressure values.展开更多
Robotic inguinal hernia repair remains in the early stages of implementation,and its potential advantages over the laparoscopic approach are still a matter of debate.This narrative review aims to summarize the finding...Robotic inguinal hernia repair remains in the early stages of implementation,and its potential advantages over the laparoscopic approach are still a matter of debate.This narrative review aims to summarize the findingsof major systematic reviews and randomized controlled trials and explore variables not adequately addressed in those studies.The literature review indicates that robotic inguinal hernia repair is associated with longer operative times but has improved ergonomics compared with laparoscopy.It is a safe procedure that results in a reduced inflammatory response,similar complication rates,and no significantdifference in acute postoperative pain.Although it involves higher direct costs,its cost-effectiveness remains unclear owing to a lack of analysis including indirect costs.Ongoing controversy continues regarding long-term benefits.The most recent systematic review pointed towards lower recurrence rates with robotic surgery,although randomized controlled trials have not validated this finding.Data on chronic pain are currently insufficientto draw firmconclusions.Further studies are needed to assess its use in complex cases and the role of novel techniques.展开更多
Fissured rocks are prevalent in geotechnical engineering and can significantlyimpact the stability of engineering structures.Microbial-induced carbonate precipitation(MICP)technology provides an ecofriendly solution f...Fissured rocks are prevalent in geotechnical engineering and can significantlyimpact the stability of engineering structures.Microbial-induced carbonate precipitation(MICP)technology provides an ecofriendly solution for repairing fissuredrocks.To optimize repair effectiveness,this study firstinvestigated the effects of environmental factors on bacterial growth,urease activity,and calcium carbonate yield.The optimal MICP scheme was determined to be a pH of 9,a temperature of 25℃,and a cementation solution concentration of 0.5 mol/L.Subsequently,the sandstone specimens with various fissureapertures were repaired using MICP with different bacterial concentrations.Dynamic tests were carried out on the repaired specimens using a split Hopkinson pressure bar system.The experimental results indicate that the dynamic strength of the MICP-repaired specimens positively correlates with strain rate,but decreases with increasing bacterial concentration and fissureaperture.These factors have little effect on the progressive failure behavior.Surface cracks were mainly compression-shear cracks in the repair area and tensile-shear cracks at the end of the specimen.Moreover,the crystal morphology observed by scanning electron microscope indicates that MICP primarily produces vaterite crystals,and lower bacterial concentrations favor the formation of more stable calcite crystals,thereby enhancing the cementitious properties.Furthermore,X-ray computed tomography demonstrates an uneven distribution of calcium carbonate within fissures,with higher fillingrates observed at the injection end and at the bottom of the fissures.Lower bacterial concentrations and smaller fissureapertures are conducive to more uniform distribution and increased fillingrate of calcium carbonate,with fissureaperture exerting a more dominant influence.展开更多
The central nervous system(CNS)does not function in isolation-it engages in continuous molecular dialogue with the vascular and immune systems.Traditionally,the blood-brain barrier(BBB)was portrayed solely as an imper...The central nervous system(CNS)does not function in isolation-it engages in continuous molecular dialogue with the vascular and immune systems.Traditionally,the blood-brain barrier(BBB)was portrayed solely as an impermeable wall,safeguarding the CNS by excluding blood-derived molecules and circulating cells.However,this view has evolved.The BBB is now recognized as a dynamic interface that selectively regulates the exchange of signals,cells.展开更多
Automated Program Repair(APR)techniques have shown significant potential in mitigating the cost and complexity associated with debugging by automatically generating corrective patches for software defects.Despite cons...Automated Program Repair(APR)techniques have shown significant potential in mitigating the cost and complexity associated with debugging by automatically generating corrective patches for software defects.Despite considerable progress in APR methodologies,existing approaches frequently lack contextual awareness of runtime behaviors and structural intricacies inherent in buggy source code.In this paper,we propose a novel APR approach that integrates attention mechanisms within an autoencoder-based framework,explicitly utilizing structural code affinity and execution context correlation derived from stack trace analysis.Our approach begins with an innovative preprocessing pipeline,where code segments and stack traces are transformed into tokenized representations.Subsequently,the BM25 ranking algorithm is employed to quantitatively measure structural code affinity and execution context correlation,identifying syntactically and semantically analogous buggy code snippets and relevant runtime error contexts from extensive repositories.These extracted features are then encoded via an attention-enhanced autoencoder model,specifically designed to capture significant patterns and correlations essential for effective patch generation.To assess the efficacy and generalizability of our proposed method,we conducted rigorous experimental comparisons against DeepFix,a state-of-the-art APR system,using a substantial dataset comprising 53,478 studentdeveloped C programs.Experimental outcomes indicate that our model achieves a notable bug repair success rate of approximately 62.36%,representing a statistically significant performance improvement of over 6%compared to the baseline.Furthermore,a thorough K-fold cross-validation reinforced the consistency,robustness,and reliability of our method across diverse subsets of the dataset.Our findings present the critical advantage of integrating attentionbased learning with code structural and execution context features in APR tasks,leading to improved accuracy and practical applicability.Future work aims to extend the model’s applicability across different programming languages,systematically optimize hyperparameters,and explore alternative feature representation methods to further enhance debugging efficiency and effectiveness.展开更多
Spinal cord injury(SCI)is a debilitating ailment that leads to the loss of motor and sensory functions,often leaving the patient paralyzed below the injury site(Chen et al.,2013).Globally around 250,000-300,000 people...Spinal cord injury(SCI)is a debilitating ailment that leads to the loss of motor and sensory functions,often leaving the patient paralyzed below the injury site(Chen et al.,2013).Globally around 250,000-300,000 people are diagnosed with SCI annually(Singh et al.,2014),and while this number appears quite low,the effect that an SCI has on the patient’s quality of life is drastic,due to the current difficulties to comprehensively treat this illness.The cost of patient care can also be quite costly,amounting to an estimated$1.69 billion in healthcare costs in the USA alone(Mahabaleshwarkar and Khanna,2014).展开更多
The blood-spinal cord barrier is crucial for preserving homeostasis of the central nervous system.After spinal cord injury,autophagic flux within endothelial cells is disrupted,compromising the integrity of the blood-...The blood-spinal cord barrier is crucial for preserving homeostasis of the central nervous system.After spinal cord injury,autophagic flux within endothelial cells is disrupted,compromising the integrity of the blood-spinal cord barrier.This disruption facilitates extensive infiltration of inflammatory cells,resulting in exacerbated neuroinflammatory responses,neuronal death,and impaired neuronal regeneration.Previous research has demonstrated that photobiomodulation promotes the regeneration of damaged nerves following spinal cord injury by inhibiting the recruitment of inflammatory cells to the injured site and restoring neuronal mitochondrial function.However,the precise mechanisms by which photobiomodulation regulates neuroinflammation remain incompletely elucidated.In this study,we established a mouse model of spinal cord injury and assessed the effects of photobiomodulation treatment.Photobiomodulation effectively cleared damaged mitochondria from endothelial cells in mice,promoting recovery of hindlimb motor function.Using microvascular endothelial bEnd.3 cells subjected to oxygen-glucose deprivation,we found that the effects of photobiomodulation were mediated through activation of the PINK1/Parkin pathway.Additionally,photobiomodulation reduced mitochondrial oxidative stress levels and increased the expression of tight junction proteins within the blood-spinal cord barrier.Our findings suggest that photobiomodulation activates mitochondrial autophagy in endothelial cells through the PINK1/Parkin pathway,thereby promoting repair of the blood-spinal cord barrier following spinal cord injury.展开更多
Exogenous neural stem cell transplantation has become one of the most promising treatment methods for chronic stroke.Recent studies have shown that most ischemia-reperfusion model rats recover spontaneously after inju...Exogenous neural stem cell transplantation has become one of the most promising treatment methods for chronic stroke.Recent studies have shown that most ischemia-reperfusion model rats recover spontaneously after injury,which limits the ability to observe long-term behavioral recovery.Here,we used a severe stroke rat model with 150 minutes of ischemia,which produced severe behavioral deficiencies that persisted at 12 weeks,to study the therapeutic effect of neural stem cells on neural restoration in chronic stroke.Our study showed that stroke model rats treated with human neural stem cells had long-term sustained recovery of motor function,reduced infarction volume,long-term human neural stem cell survival,and improved local inflammatory environment and angiogenesis.We also demonstrated that transplanted human neural stem cells differentiated into mature neurons in vivo,formed stable functional synaptic connections with host neurons,and exhibited the electrophysiological properties of functional mature neurons,indicating that they replaced the damaged host neurons.The findings showed that human fetal-derived neural stem cells had long-term effects for neurological recovery in a model of severe stroke,which suggests that human neural stem cells-based therapy may be effective for repairing damaged neural circuits in stroke patients.展开更多
Mesenchymal stromal cell transplantation is an effective and promising approach for treating various systemic and diffuse diseases.However,the biological characteristics of transplanted mesenchymal stromal cells in hu...Mesenchymal stromal cell transplantation is an effective and promising approach for treating various systemic and diffuse diseases.However,the biological characteristics of transplanted mesenchymal stromal cells in humans remain unclear,including cell viability,distribution,migration,and fate.Conventional cell tracing methods cannot be used in the clinic.The use of superparamagnetic iron oxide nanoparticles as contrast agents allows for the observation of transplanted cells using magnetic resonance imaging.In 2016,the National Medical Products Administration of China approved a new superparamagnetic iron oxide nanoparticle,Ruicun,for use as a contrast agent in clinical trials.In the present study,an acute hemi-transection spinal cord injury model was established in beagle dogs.The injury was then treated by transplantation of Ruicun-labeled mesenchymal stromal cells.The results indicated that Ruicunlabeled mesenchymal stromal cells repaired damaged spinal cord fibers and partially restored neurological function in animals with acute spinal cord injury.T2*-weighted imaging revealed low signal areas on both sides of the injured spinal cord.The results of quantitative susceptibility mapping with ultrashort echo time sequences indicated that Ruicun-labeled mesenchymal stromal cells persisted stably within the injured spinal cord for over 4 weeks.These findings suggest that magnetic resonance imaging has the potential to effectively track the migration of Ruicun-labeled mesenchymal stromal cells and assess their ability to repair spinal cord injury.展开更多
The plasma membrane(PM)plays an essential role in maintaining cell homeostasis,therefore,timely and effective repair of damage caused by factors such as mechanical rupture,pore-forming toxins,or pore-forming proteins ...The plasma membrane(PM)plays an essential role in maintaining cell homeostasis,therefore,timely and effective repair of damage caused by factors such as mechanical rupture,pore-forming toxins,or pore-forming proteins is crucial for cell survival.PM damage induces membrane rupture and stimulates an immune response.However,damage resulting from regulated cell death processes,including pyroptosis,ferroptosis,and necroptosis,cannot be repaired by simple sealing mechanisms and thus,requires specialized repair machinery.Recent research has identified a PM repair mechanism of regulated cell death-related injury,mediated by the endosomal sorting complexes required for transport(ESCRT)machinery.Here,we review recent progress in elucidating the ESCRT machinery-mediated repair mechanism of PM injury,with particular focus on processes related to regulated cell death.This overview,along with continued research in this field,may provide novel insights into therapeutic targets for diseases associated with dysregulation of regulated cell death pathways.展开更多
CD47 is a ubiquitous and pleiotropic cell-surface receptor.Disrupting CD47 enhances injury repair in various tissues but the role of CD47 has not been studied in bone injuries.In a murine closed-fracture model,CD47-nu...CD47 is a ubiquitous and pleiotropic cell-surface receptor.Disrupting CD47 enhances injury repair in various tissues but the role of CD47 has not been studied in bone injuries.In a murine closed-fracture model,CD47-null mice showed decreased callus bone formation as assessed by microcomputed tomography 10 days post-fracture and increased fibrous volume as determined by histology.To understand the cellular basis for this phenotype,mesenchymal progenitors(MSC)were harvested from bone marrow.CD47-null MSC showed decreased large fibroblast colony formation(CFU-F),significantly less proliferation,and fewer cells in Sphase,although osteoblast differentiation was unaffected.However,consistent with prior research,CD47-null endothelial cells showed increased proliferation relative to WT cells.Similarly,in a murine ischemic fracture model,CD47-null mice showed reduced fracture callus size due to a reduction in bone relative to WT 15 days-post fracture.Consistent with our in vitro results,in vivo EdU labeling showed decreased cell proliferation in the callus of CD47-null mice,while staining for CD31 and endomucin demonstrated increased endothelial cell density.Finally,WT mice with ischemic fracture that were administered a CD47 morpholino,which blocks CD47 protein production,showed a callus phenotype similar to that of ischemic fractures in CD47-null mice,suggesting the phenotype was not due to developmental changes in the knockout mice.Thus,inhibition of CD47 during bone healing reduces both non-ischemic and ischemic fracture healing,in part,by decreasing MSC proliferation.Furthermore,the increase in endothelial cell proliferation and early blood vessel density caused by CD47 disruption is not sufficient to overcome MSC dysfunction.展开更多
The global demand for effective skin injury treatments has prompted the exploration of tissue engineering solutions.While three-dimensional(3D)bioprinting has shown promise,challenges persist with respect to achieving...The global demand for effective skin injury treatments has prompted the exploration of tissue engineering solutions.While three-dimensional(3D)bioprinting has shown promise,challenges persist with respect to achieving timely and compatible solutions to treat diverse skin injuries.In situ bioprinting has emerged as a key new technology,since it reduces risks during the implantation of printed scaffolds and demonstrates superior therapeutic effects.However,maintaining printing fidelity during in situ bioprinting remains a critical challenge,particularly with respect to model layering and path planning.This study proposes a novel optimization-based conformal path planning strategy for in situ bioprinting-based repair of complex skin injuries.This strategy employs constrained optimization to identify optimal waypoints on a point cloud-approximated curved surface,thereby ensuring a high degree of similarity between predesigned planar and surface-mapped 3D paths.Furthermore,this method is applicable for skin wound treatments,since it generates 3D-equidistant zigzag curves along surface tangents and enables multi-layer conformal path planning to facilitate the treatment of volumetric injuries.Furthermore,the proposed algorithm was found to be a feasible and effective treatment in a murine back injury model as well as in other complex models,thereby showcasing its potential to guide in situ bioprinting,enhance bioprinting fidelity,and facilitate improvement of clinical outcomes.展开更多
BACKGROUND Meniscal tears are one of the most common knee injuries.After the diagnosis of a meniscal tear has been made,there are several factors physicians use to guide clinical decision-making.The influence of time ...BACKGROUND Meniscal tears are one of the most common knee injuries.After the diagnosis of a meniscal tear has been made,there are several factors physicians use to guide clinical decision-making.The influence of time between injury and isolated meniscus repair on patient outcomes is not well described.Assessing this relationship is important as it may influence clinical decision-making and can add to the preoperative patient education process.We hypothesized that increasing the time from injury to meniscus surgery would worsen postoperative outcomes.AIM To investigate the current literature for data on the relationship between time between meniscus injury and repair on patient outcomes.METHODS PubMed,Academic Search Complete,MEDLINE,CINAHL,and SPORTDiscus were searched for studies published between January 1,1995 and July 13,2023 on isolated meniscus repair.Exclusion criteria included concomitant ligament surgery,incomplete outcomes or time to surgery data,and meniscectomies.Patient demographics,time to injury,and postoperative outcomes from each study were abstracted and analyzed.RESULTS Five studies met all inclusion and exclusion criteria.There were 204(121 male,83 female)patients included.Three of five(60%)studies determined that time between injury and surgery was not statistically significant for postoperative Lysholm scores(P=0.62),Tegner scores(P=0.46),failure rate(P=0.45,P=0.86),and International Knee Documentation Committee scores(P=0.65).Two of five(40%)studies found a statistically significant increase in Lysholm scores with shorter time to surgery(P=0.03)and a statistically significant association between progression of medial meniscus extrusion ratio(P=0.01)and increasing time to surgery.CONCLUSION Our results do not support the hypothesis that increased time from injury to isolated meniscus surgery worsens postoperative outcomes.Decision-making primarily based on injury interval is thus not recommended.展开更多
Successful polyethylene glycol fusion(PEG-fusion)of severed axons following peripheral nerve injuries for PEG-fused axons has been reported to:(1)rapidly restore electrophysiological continuity;(2)prevent distal Walle...Successful polyethylene glycol fusion(PEG-fusion)of severed axons following peripheral nerve injuries for PEG-fused axons has been reported to:(1)rapidly restore electrophysiological continuity;(2)prevent distal Wallerian Degeneration and maintain their myelin sheaths;(3)promote primarily motor,voluntary behavioral recoveries as assessed by the Sciatic Functional Index;and,(4)rapidly produce correct and incorrect connections in many possible combinations that produce rapid and extensive recovery of functional peripheral nervous system/central nervous system connections and reflex(e.g.,toe twitch)or voluntary behaviors.The preceding companion paper describes sensory terminal field reo rganization following PEG-fusion repair of sciatic nerve transections or ablations;howeve r,sensory behavioral recovery has not been explicitly explored following PEG-fusion repair.In the current study,we confirmed the success of PEG-fusion surgeries according to criteria(1-3)above and more extensively investigated whether PEG-fusion enhanced mechanical nociceptive recovery following sciatic transection in male and female outbred Sprague-Dawley and inbred Lewis rats.Mechanical nociceptive responses were assessed by measuring withdrawal thresholds using von Frey filaments on the dorsal and midplantar regions of the hindpaws.Dorsal von Frey filament tests were a more reliable method than plantar von Frey filament tests to assess mechanical nociceptive sensitivity following sciatic nerve transections.Baseline withdrawal thresholds of the sciatic-mediated lateral dorsal region differed significantly across strain but not sex.Withdrawal thresholds did not change significantly from baseline in chronic Unoperated and Sham-operated rats.Following sciatic transection,all rats exhibited severe hyposensitivity to stimuli at the lateral dorsal region of the hindpaw ipsilateral to the injury.However,PEG-fused rats exhibited significantly earlier return to baseline withdrawal thresholds than Negative Control rats.Furthermore,PEG-fused rats with significantly improved Sciatic Functional Index scores at or after 4 weeks postoperatively exhibited yet-earlier von Frey filament recove ry compared with those without Sciatic Functional Index recovery,suggesting a correlation between successful PEG-fusion and both motor-dominant and sensory-dominant behavioral recoveries.This correlation was independent of the sex or strain of the rat.Furthermore,our data showed that the acceleration of von Frey filament sensory recovery to baseline was solely due to the PEG-fused sciatic nerve and not saphenous nerve collateral outgrowths.No chronic hypersensitivity developed in any rat up to 12 weeks.All these data suggest that PEG-fusion repair of transection peripheral nerve injuries co uld have important clinical benefits.展开更多
The exchange of information and materials between organelles plays a crucial role in regulating cellular physiological functions and metabolic levels.Mitochondria-associated endoplasmic reticulum membranes serve as ph...The exchange of information and materials between organelles plays a crucial role in regulating cellular physiological functions and metabolic levels.Mitochondria-associated endoplasmic reticulum membranes serve as physical contact channels between the endoplasmic reticulum membrane and the mitochondrial outer membrane,formed by various proteins and protein complexes.This microstructural domain mediates several specialized functions,including calcium(Ca^(2+))signaling,autophagy,mitochondrial morphology,oxidative stress response,and apoptosis.Notably,the dysregulation of Ca^(2+)signaling mediated by mitochondria-associated endoplasmic reticulum membranes is a critical factor in the pathogenesis of neurological diseases.Certain proteins or protein complexes within these membranes directly or indirectly regulate the distance between the endoplasmic reticulum and mitochondria,as well as the transduction of Ca^(2+)signaling.Conversely,Ca^(2+)signaling mediated by mitochondria-associated endoplasmic reticulum membranes influences other mitochondria-associated endoplasmic reticulum membraneassociated functions.These functions can vary significantly across different neurological diseases—such as ischemic stroke,traumatic brain injury,Alzheimer's disease,Parkinson's disease,amyotrophic lateral sclerosis,and Huntington's disease—and their respective stages of progression.Targeted modulation of these disease-related pathways and functional proteins can enhance neurological function and promote the regeneration and repair of damaged neurons.Therefore,mitochondria-associated endoplasmic reticulum membranes-mediated Ca^(2+)signaling plays a pivotal role in the pathological progression of neurological diseases and represents a significant potential therapeutic target.This review focuses on the effects of protein complexes in mitochondria-associated endoplasmic reticulum membranes and the distinct roles of mitochondria-associated endoplasmic reticulum membranes-mediated Ca^(2+)signaling in neurological diseases,specifically highlighting the early protective effects and neuronal damage that can result from prolonged mitochondrial Ca^(2+)overload or deficiency.This article provides a comprehensive analysis of the various mechanisms of Ca^(2+)signaling mediated by mitochondria-associated endoplasmic reticulum membranes in neurological diseases,contributing to the exploration of potential therapeutic targets for promoting neuroprotection and nerve repair.展开更多
Four types of Mg-5Zn porous scaffolds with different pore geometries,including body-centered cubic(bcc),the rhombic dodecahedron(RD),gyroid(G),and primitive(P)types,were designed and fabricated using selective laser m...Four types of Mg-5Zn porous scaffolds with different pore geometries,including body-centered cubic(bcc),the rhombic dodecahedron(RD),gyroid(G),and primitive(P)types,were designed and fabricated using selective laser melting.Their forming quality,compression mechanical properties,and degradation behavior were investigated.Results indicate that the fabricated scaffolds exhibit good dimensional accuracy,and the surface chemical polishing treatment significantly improves the forming quality and reduces porosity error in porous scaffolds.Compared to the ones with rod structures(bcc,RD),the scaffolds with surface structures(G,P)have less powder particle adhesion.The G porous scaffold exhibits the best forming quality for the same design porosity.The predominant failure mode of scaffolds during compression is a 45°shear fracture.At a porosity of 75%,the compression property of all scaffolds meets the compressive property requirements of cancellous bone,while bcc and G structures show relatively better compression property.After immersion in Hank's solution for 168 h,the B-2-75% pore structure scaffold exhibits severe localized corrosion,with fractures in partial pillar connections.In contrast,the G-3-75% pore structure scaffold mainly undergoes uniform corrosion,maintaining structural integrity,and its corrosion rate and loss of compressive properties are less than those of the B-2-75%structure.After comparison,the G-pore structure scaffold is preferred.展开更多
Background:Flexor tendon injuries in zones II–V are challenging because of the risk of adhesions and rupture.Although early passive mobilization limits rupture,it often compromises the functional recovery.Recent appr...Background:Flexor tendon injuries in zones II–V are challenging because of the risk of adhesions and rupture.Although early passive mobilization limits rupture,it often compromises the functional recovery.Recent approaches favor early active mobilization with strong,multi-stranded core sutures to enhance outcomes.This study evaluated early active mobilization after eight-strand core repair in a tertiary care setting.Methods:In this prospective study,143 tendons from 30 patients who underwent surgery were followed up.The injured tendons were repaired using an eight-strand cross-locked cruciate technique with a double-stranded 4-0 suture,providing the tensile strength of eight strands with the same number of suture passes as in traditional four-core repairs,thereby reducing operative time without increasing bulk.Early active mobilization was initiated on postoperative day 2.The patients underwent digitally supervised physiotherapy and were monitored using a dedicated WhatsApp group,which enabled real-time guidance and compliance monitoring.The outcomes were measured in terms of total active motion,grip strength,pinch strength,time to return to work,postoperative pain,and complications.Results:Of the 30 patients,28(93.3%)had fair-to-excellent outcomes,whereas only 2(6.7%)had poor outcomes.Most patients(93.3%)returned to work within 12 weeks postoperatively.Four(13.3%)patients had complications,such as wound infection and skin necrosis.The patients showed significant changes in grip strength(45.2%)and pinch strength(70.7%)between weeks 8 and 12.No tendon ruptures were observed.Conclusion:The eight-core suturing technique used for flexor tendon repair withstood the forces of early active mobilization,which began on the second day after surgery,resulting in fair-to-excellent outcomes.It supports digitally supervised physiotherapy through app-based monitoring,enhancing patient compliance,and reducing reliance on in-person therapy sessions.This combination led to excellent functional recovery with minimal complications.展开更多
BACKGROUND Descending thoracic aortic aneurysms are dangerous and have to be treated quickly.The primary treatment methods are thoracic endovascular aortic repair(TEVAR)and open surgical repair(OSR).The comparative ef...BACKGROUND Descending thoracic aortic aneurysms are dangerous and have to be treated quickly.The primary treatment methods are thoracic endovascular aortic repair(TEVAR)and open surgical repair(OSR).The comparative effectiveness and safety of TEVAR and OSR were evaluated in this meta-analysis,focusing on perioperative and long-term outcomes.AIM To compare and contrast the efficacy and safety of TEVAR vs OSR in the treatment of descending thoracic aortic aneurysms.This study aims to assess both perioperative and long-term outcomes through a systematic review and metaanalysis.METHODS A comprehensive search of PubMed,EMBASE,and Cochrane was conducted from inception to January 2025.Baseline characteristics and outcomes were evaluated.Odds ratios(OR)for dichotomous data and mean differences for continuous data with 95%confidence intervals(CI)were analyzed using random-effects models.RESULTS A meta-analysis of 21 studies involving 29465 patients(8261 TEVAR;21204 OR)showed TEVAR associated with lower operative mortality(OR=0.60,95%CI:0.42-0.85,P=0.004),shorter intensive care unit(-2.94 days,95%CI:-4.76 to-1.12,P=0.002)and hospital stays(-7.35 days,95%CI:-10.54 to-4.17,P<0.00001),and reduced rates of paraplegia(OR=0.44,95%CI:0.27-0.73,P=0.002),spinal ischemia(OR=0.30,95%CI:0.16-0.56,P=0.0002),renal failure(OR=0.29,95%CI:0.14-0.61,P=0.001),and wound infections(OR=0.28,95%CI:0.13-0.61,P=0.001).However,TEVAR had higher rates of vascular complications.No significant differences were noted in 1-year and 5-year mortality rates,the rate of non-elective surgery,neurological complications,or stroke rates.CONCLUSION Compared to EVAR,TEVAR revealed lower operative mortality and better perioperative outcomes across all indicators,including hospital and intensive care unit stays,as well as fewer complications,except for those related to vascular problems.Mortality results were also similar in the long run;consequently,more research is required concerning the long-term durability.展开更多
基金National Key Research and Development Program of China,Grant/Award Number:2023YFC2410403。
文摘Background:Rats are often used to prepare skin defect models.However,the skin defect sizes of the models prepared by researchers are different,and the lack of consensus on the critical-size defect makes it difficult to compare their research results.Methods:The time for wound closure was evaluated and recorded through gross observation.The regression equation between the healing time and the diameter of skin defect was established,which can be used to predict the healing time for a certain skin defect size in rats.Histochemical and immunohistochemical staining was used to observe the regeneration and reconstruction of skin appendages,and the functional skin repair was quantitatively scored.Results:The critical-size defect of rats was determined based on the maximum capacity of structural skin repair,and the functional skin repair was quantitatively scored based on the regeneration and reconstruction of skin appendages.The allowable range of critical-size skin defect of SD rats lies between 45 and 50 mm in diameter.The concept of structural repair and the category of functional repair of injured skin are put forward.The regression equation between the structural skin healing time and defect diameters is established.Conclusion:The allowable range of skin critical-size defect of SD rats lies between 45 and 50 mm in diameter.The regression equation between the structural skin healing time and defect diameters can be used to predict the healing time for a certain skin defect size in rats.
基金Funded by the National Natural Science Foundation of China(No.52473077)China Three Gorges Corporation(No.202403190)。
文摘In ultraviolet cured-in-place-pipe(UV-CIPP)pipeline rehabilitation,resin performance critically determines repair effectiveness.Current UV-curable resins exhibit high volatile organic compound(VOC)emissions and inadequate post-cure toughness,which compromise fatigue resistance during service.To address these issues,we synthesized hydroxyl-terminated polyurethane acrylate prepolymers using diphenylmethane diisocyanate(MDI),polypropylene glycol(PPG),and hydroxyethyl methacrylate(HEMA).Fourier transform infrared spectroscopy(FTIR)confirmed successful prepolymer synthesis.We developed UV-curable resins by incorporating various crosslinking monomers and optimized the formulations through mechanical property analysis.Testing revealed that the polyurethane-acrylic UV-cured resin system combines polyurethane's mechanical excellence with acrylics'high UV-curing activity.The PPG200/MDI/HEMA formulation achieved superior performance,with a tensile strength of 55.31 MPa,an impact toughness of 22.7 kJ/m^(2),and a heat deflection temperature(HDT)of 132℃.The optimized system eliminates volatile components while maintaining high reactivity,addressing critical limitations in trenchless pipeline rehabilitation.The improved mechanical properties meet the operational demands of underground pipes,suggesting practical applicability in trenchless pipeline repair.
文摘The increasing occurrence of corrosion-related damage in steel pipelines has led to the growing use of composite-based repair techniques as an efficient alternative to traditional replacement methods.Computer modeling and structural analysis were performed for the repair reinforcement of a steel pipeline with a composite bandage.A preliminary analysis of possible contact interaction schemes was implemented based on the theory of cylindrical shells,taking into account transverse shear deformations.The finite element method was used for a detailed study of the stress state of the composite bandage and the reinforced section of the pipeline.The limit state of the reinforced section was assessed based on the von Mises criterion for steel and the Tsai-Wu criterion for composites.The effectiveness of the repair was demonstrated on a pipeline whose wall thickness had decreased by 20%as a result of corrosion damage.At a nominal pressure of P=6 MPa,the maximum normal stress in the weakened area reached 381 MPa.The installation of a composite bandage reduced this stress to 312 MPa,making the repaired section virtually as strong as the undamaged pipeline.Due to the linearity of the problem,the results obtained can be easily used to find critical internal pressure values.
文摘Robotic inguinal hernia repair remains in the early stages of implementation,and its potential advantages over the laparoscopic approach are still a matter of debate.This narrative review aims to summarize the findingsof major systematic reviews and randomized controlled trials and explore variables not adequately addressed in those studies.The literature review indicates that robotic inguinal hernia repair is associated with longer operative times but has improved ergonomics compared with laparoscopy.It is a safe procedure that results in a reduced inflammatory response,similar complication rates,and no significantdifference in acute postoperative pain.Although it involves higher direct costs,its cost-effectiveness remains unclear owing to a lack of analysis including indirect costs.Ongoing controversy continues regarding long-term benefits.The most recent systematic review pointed towards lower recurrence rates with robotic surgery,although randomized controlled trials have not validated this finding.Data on chronic pain are currently insufficientto draw firmconclusions.Further studies are needed to assess its use in complex cases and the role of novel techniques.
基金support from the National Key R&D Program of China(Grant No.2023YFC3081500)the National Natural Science Foundation of China(Grant Nos.52225904 and 52039007).
文摘Fissured rocks are prevalent in geotechnical engineering and can significantlyimpact the stability of engineering structures.Microbial-induced carbonate precipitation(MICP)technology provides an ecofriendly solution for repairing fissuredrocks.To optimize repair effectiveness,this study firstinvestigated the effects of environmental factors on bacterial growth,urease activity,and calcium carbonate yield.The optimal MICP scheme was determined to be a pH of 9,a temperature of 25℃,and a cementation solution concentration of 0.5 mol/L.Subsequently,the sandstone specimens with various fissureapertures were repaired using MICP with different bacterial concentrations.Dynamic tests were carried out on the repaired specimens using a split Hopkinson pressure bar system.The experimental results indicate that the dynamic strength of the MICP-repaired specimens positively correlates with strain rate,but decreases with increasing bacterial concentration and fissureaperture.These factors have little effect on the progressive failure behavior.Surface cracks were mainly compression-shear cracks in the repair area and tensile-shear cracks at the end of the specimen.Moreover,the crystal morphology observed by scanning electron microscope indicates that MICP primarily produces vaterite crystals,and lower bacterial concentrations favor the formation of more stable calcite crystals,thereby enhancing the cementitious properties.Furthermore,X-ray computed tomography demonstrates an uneven distribution of calcium carbonate within fissures,with higher fillingrates observed at the injection end and at the bottom of the fissures.Lower bacterial concentrations and smaller fissureapertures are conducive to more uniform distribution and increased fillingrate of calcium carbonate,with fissureaperture exerting a more dominant influence.
基金supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under Award Number K02NS110973 and R01NS126498(to MAP).
文摘The central nervous system(CNS)does not function in isolation-it engages in continuous molecular dialogue with the vascular and immune systems.Traditionally,the blood-brain barrier(BBB)was portrayed solely as an impermeable wall,safeguarding the CNS by excluding blood-derived molecules and circulating cells.However,this view has evolved.The BBB is now recognized as a dynamic interface that selectively regulates the exchange of signals,cells.
文摘Automated Program Repair(APR)techniques have shown significant potential in mitigating the cost and complexity associated with debugging by automatically generating corrective patches for software defects.Despite considerable progress in APR methodologies,existing approaches frequently lack contextual awareness of runtime behaviors and structural intricacies inherent in buggy source code.In this paper,we propose a novel APR approach that integrates attention mechanisms within an autoencoder-based framework,explicitly utilizing structural code affinity and execution context correlation derived from stack trace analysis.Our approach begins with an innovative preprocessing pipeline,where code segments and stack traces are transformed into tokenized representations.Subsequently,the BM25 ranking algorithm is employed to quantitatively measure structural code affinity and execution context correlation,identifying syntactically and semantically analogous buggy code snippets and relevant runtime error contexts from extensive repositories.These extracted features are then encoded via an attention-enhanced autoencoder model,specifically designed to capture significant patterns and correlations essential for effective patch generation.To assess the efficacy and generalizability of our proposed method,we conducted rigorous experimental comparisons against DeepFix,a state-of-the-art APR system,using a substantial dataset comprising 53,478 studentdeveloped C programs.Experimental outcomes indicate that our model achieves a notable bug repair success rate of approximately 62.36%,representing a statistically significant performance improvement of over 6%compared to the baseline.Furthermore,a thorough K-fold cross-validation reinforced the consistency,robustness,and reliability of our method across diverse subsets of the dataset.Our findings present the critical advantage of integrating attentionbased learning with code structural and execution context features in APR tasks,leading to improved accuracy and practical applicability.Future work aims to extend the model’s applicability across different programming languages,systematically optimize hyperparameters,and explore alternative feature representation methods to further enhance debugging efficiency and effectiveness.
基金supported by the Irish Research Council under the Government of Ireland Postdoctoral Fellowship Project ID-GOIPD/2023/1431(to AS).
文摘Spinal cord injury(SCI)is a debilitating ailment that leads to the loss of motor and sensory functions,often leaving the patient paralyzed below the injury site(Chen et al.,2013).Globally around 250,000-300,000 people are diagnosed with SCI annually(Singh et al.,2014),and while this number appears quite low,the effect that an SCI has on the patient’s quality of life is drastic,due to the current difficulties to comprehensively treat this illness.The cost of patient care can also be quite costly,amounting to an estimated$1.69 billion in healthcare costs in the USA alone(Mahabaleshwarkar and Khanna,2014).
基金supported by the National Natural Science Foundation of China,No.82471411(to ZW and TD)the Key Research and DevelopmentProgram of Shaanxi Province,No.2023-ZDLSF-12(to TD).
文摘The blood-spinal cord barrier is crucial for preserving homeostasis of the central nervous system.After spinal cord injury,autophagic flux within endothelial cells is disrupted,compromising the integrity of the blood-spinal cord barrier.This disruption facilitates extensive infiltration of inflammatory cells,resulting in exacerbated neuroinflammatory responses,neuronal death,and impaired neuronal regeneration.Previous research has demonstrated that photobiomodulation promotes the regeneration of damaged nerves following spinal cord injury by inhibiting the recruitment of inflammatory cells to the injured site and restoring neuronal mitochondrial function.However,the precise mechanisms by which photobiomodulation regulates neuroinflammation remain incompletely elucidated.In this study,we established a mouse model of spinal cord injury and assessed the effects of photobiomodulation treatment.Photobiomodulation effectively cleared damaged mitochondria from endothelial cells in mice,promoting recovery of hindlimb motor function.Using microvascular endothelial bEnd.3 cells subjected to oxygen-glucose deprivation,we found that the effects of photobiomodulation were mediated through activation of the PINK1/Parkin pathway.Additionally,photobiomodulation reduced mitochondrial oxidative stress levels and increased the expression of tight junction proteins within the blood-spinal cord barrier.Our findings suggest that photobiomodulation activates mitochondrial autophagy in endothelial cells through the PINK1/Parkin pathway,thereby promoting repair of the blood-spinal cord barrier following spinal cord injury.
文摘Exogenous neural stem cell transplantation has become one of the most promising treatment methods for chronic stroke.Recent studies have shown that most ischemia-reperfusion model rats recover spontaneously after injury,which limits the ability to observe long-term behavioral recovery.Here,we used a severe stroke rat model with 150 minutes of ischemia,which produced severe behavioral deficiencies that persisted at 12 weeks,to study the therapeutic effect of neural stem cells on neural restoration in chronic stroke.Our study showed that stroke model rats treated with human neural stem cells had long-term sustained recovery of motor function,reduced infarction volume,long-term human neural stem cell survival,and improved local inflammatory environment and angiogenesis.We also demonstrated that transplanted human neural stem cells differentiated into mature neurons in vivo,formed stable functional synaptic connections with host neurons,and exhibited the electrophysiological properties of functional mature neurons,indicating that they replaced the damaged host neurons.The findings showed that human fetal-derived neural stem cells had long-term effects for neurological recovery in a model of severe stroke,which suggests that human neural stem cells-based therapy may be effective for repairing damaged neural circuits in stroke patients.
基金supported by the National Key R&D Program of China,Nos.2017YFA0104302(to NG and XM)and 2017YFA0104304(to BW and ZZ)
文摘Mesenchymal stromal cell transplantation is an effective and promising approach for treating various systemic and diffuse diseases.However,the biological characteristics of transplanted mesenchymal stromal cells in humans remain unclear,including cell viability,distribution,migration,and fate.Conventional cell tracing methods cannot be used in the clinic.The use of superparamagnetic iron oxide nanoparticles as contrast agents allows for the observation of transplanted cells using magnetic resonance imaging.In 2016,the National Medical Products Administration of China approved a new superparamagnetic iron oxide nanoparticle,Ruicun,for use as a contrast agent in clinical trials.In the present study,an acute hemi-transection spinal cord injury model was established in beagle dogs.The injury was then treated by transplantation of Ruicun-labeled mesenchymal stromal cells.The results indicated that Ruicunlabeled mesenchymal stromal cells repaired damaged spinal cord fibers and partially restored neurological function in animals with acute spinal cord injury.T2*-weighted imaging revealed low signal areas on both sides of the injured spinal cord.The results of quantitative susceptibility mapping with ultrashort echo time sequences indicated that Ruicun-labeled mesenchymal stromal cells persisted stably within the injured spinal cord for over 4 weeks.These findings suggest that magnetic resonance imaging has the potential to effectively track the migration of Ruicun-labeled mesenchymal stromal cells and assess their ability to repair spinal cord injury.
文摘The plasma membrane(PM)plays an essential role in maintaining cell homeostasis,therefore,timely and effective repair of damage caused by factors such as mechanical rupture,pore-forming toxins,or pore-forming proteins is crucial for cell survival.PM damage induces membrane rupture and stimulates an immune response.However,damage resulting from regulated cell death processes,including pyroptosis,ferroptosis,and necroptosis,cannot be repaired by simple sealing mechanisms and thus,requires specialized repair machinery.Recent research has identified a PM repair mechanism of regulated cell death-related injury,mediated by the endosomal sorting complexes required for transport(ESCRT)machinery.Here,we review recent progress in elucidating the ESCRT machinery-mediated repair mechanism of PM injury,with particular focus on processes related to regulated cell death.This overview,along with continued research in this field,may provide novel insights into therapeutic targets for diseases associated with dysregulation of regulated cell death pathways.
基金supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases(NIAMS)of the National Institutes of Health(NIH)under award numbers F30AR071201(R.L.Z.)and R01 AR066028(K.D.H.)Additional research support is provided by the NIH under a training award T32TR004371(C.A.C.).
文摘CD47 is a ubiquitous and pleiotropic cell-surface receptor.Disrupting CD47 enhances injury repair in various tissues but the role of CD47 has not been studied in bone injuries.In a murine closed-fracture model,CD47-null mice showed decreased callus bone formation as assessed by microcomputed tomography 10 days post-fracture and increased fibrous volume as determined by histology.To understand the cellular basis for this phenotype,mesenchymal progenitors(MSC)were harvested from bone marrow.CD47-null MSC showed decreased large fibroblast colony formation(CFU-F),significantly less proliferation,and fewer cells in Sphase,although osteoblast differentiation was unaffected.However,consistent with prior research,CD47-null endothelial cells showed increased proliferation relative to WT cells.Similarly,in a murine ischemic fracture model,CD47-null mice showed reduced fracture callus size due to a reduction in bone relative to WT 15 days-post fracture.Consistent with our in vitro results,in vivo EdU labeling showed decreased cell proliferation in the callus of CD47-null mice,while staining for CD31 and endomucin demonstrated increased endothelial cell density.Finally,WT mice with ischemic fracture that were administered a CD47 morpholino,which blocks CD47 protein production,showed a callus phenotype similar to that of ischemic fractures in CD47-null mice,suggesting the phenotype was not due to developmental changes in the knockout mice.Thus,inhibition of CD47 during bone healing reduces both non-ischemic and ischemic fracture healing,in part,by decreasing MSC proliferation.Furthermore,the increase in endothelial cell proliferation and early blood vessel density caused by CD47 disruption is not sufficient to overcome MSC dysfunction.
基金supported in part by the National Natural Science Foundation of China(Nos.52205532 and 624B2077)the National Key Research and Development Program of China(No.2023YFB4302003).
文摘The global demand for effective skin injury treatments has prompted the exploration of tissue engineering solutions.While three-dimensional(3D)bioprinting has shown promise,challenges persist with respect to achieving timely and compatible solutions to treat diverse skin injuries.In situ bioprinting has emerged as a key new technology,since it reduces risks during the implantation of printed scaffolds and demonstrates superior therapeutic effects.However,maintaining printing fidelity during in situ bioprinting remains a critical challenge,particularly with respect to model layering and path planning.This study proposes a novel optimization-based conformal path planning strategy for in situ bioprinting-based repair of complex skin injuries.This strategy employs constrained optimization to identify optimal waypoints on a point cloud-approximated curved surface,thereby ensuring a high degree of similarity between predesigned planar and surface-mapped 3D paths.Furthermore,this method is applicable for skin wound treatments,since it generates 3D-equidistant zigzag curves along surface tangents and enables multi-layer conformal path planning to facilitate the treatment of volumetric injuries.Furthermore,the proposed algorithm was found to be a feasible and effective treatment in a murine back injury model as well as in other complex models,thereby showcasing its potential to guide in situ bioprinting,enhance bioprinting fidelity,and facilitate improvement of clinical outcomes.
文摘BACKGROUND Meniscal tears are one of the most common knee injuries.After the diagnosis of a meniscal tear has been made,there are several factors physicians use to guide clinical decision-making.The influence of time between injury and isolated meniscus repair on patient outcomes is not well described.Assessing this relationship is important as it may influence clinical decision-making and can add to the preoperative patient education process.We hypothesized that increasing the time from injury to meniscus surgery would worsen postoperative outcomes.AIM To investigate the current literature for data on the relationship between time between meniscus injury and repair on patient outcomes.METHODS PubMed,Academic Search Complete,MEDLINE,CINAHL,and SPORTDiscus were searched for studies published between January 1,1995 and July 13,2023 on isolated meniscus repair.Exclusion criteria included concomitant ligament surgery,incomplete outcomes or time to surgery data,and meniscectomies.Patient demographics,time to injury,and postoperative outcomes from each study were abstracted and analyzed.RESULTS Five studies met all inclusion and exclusion criteria.There were 204(121 male,83 female)patients included.Three of five(60%)studies determined that time between injury and surgery was not statistically significant for postoperative Lysholm scores(P=0.62),Tegner scores(P=0.46),failure rate(P=0.45,P=0.86),and International Knee Documentation Committee scores(P=0.65).Two of five(40%)studies found a statistically significant increase in Lysholm scores with shorter time to surgery(P=0.03)and a statistically significant association between progression of medial meniscus extrusion ratio(P=0.01)and increasing time to surgery.CONCLUSION Our results do not support the hypothesis that increased time from injury to isolated meniscus surgery worsens postoperative outcomes.Decision-making primarily based on injury interval is thus not recommended.
基金supported by DOD AFIRMⅢW81XWH-20-2-0029 subcontract,UT POC19-1774-13Neuraptive Therapeutics Inc.26-7724-56+1 种基金NIH R01-NS128086 grantsLone Star Paralysis gift(to GDB)。
文摘Successful polyethylene glycol fusion(PEG-fusion)of severed axons following peripheral nerve injuries for PEG-fused axons has been reported to:(1)rapidly restore electrophysiological continuity;(2)prevent distal Wallerian Degeneration and maintain their myelin sheaths;(3)promote primarily motor,voluntary behavioral recoveries as assessed by the Sciatic Functional Index;and,(4)rapidly produce correct and incorrect connections in many possible combinations that produce rapid and extensive recovery of functional peripheral nervous system/central nervous system connections and reflex(e.g.,toe twitch)or voluntary behaviors.The preceding companion paper describes sensory terminal field reo rganization following PEG-fusion repair of sciatic nerve transections or ablations;howeve r,sensory behavioral recovery has not been explicitly explored following PEG-fusion repair.In the current study,we confirmed the success of PEG-fusion surgeries according to criteria(1-3)above and more extensively investigated whether PEG-fusion enhanced mechanical nociceptive recovery following sciatic transection in male and female outbred Sprague-Dawley and inbred Lewis rats.Mechanical nociceptive responses were assessed by measuring withdrawal thresholds using von Frey filaments on the dorsal and midplantar regions of the hindpaws.Dorsal von Frey filament tests were a more reliable method than plantar von Frey filament tests to assess mechanical nociceptive sensitivity following sciatic nerve transections.Baseline withdrawal thresholds of the sciatic-mediated lateral dorsal region differed significantly across strain but not sex.Withdrawal thresholds did not change significantly from baseline in chronic Unoperated and Sham-operated rats.Following sciatic transection,all rats exhibited severe hyposensitivity to stimuli at the lateral dorsal region of the hindpaw ipsilateral to the injury.However,PEG-fused rats exhibited significantly earlier return to baseline withdrawal thresholds than Negative Control rats.Furthermore,PEG-fused rats with significantly improved Sciatic Functional Index scores at or after 4 weeks postoperatively exhibited yet-earlier von Frey filament recove ry compared with those without Sciatic Functional Index recovery,suggesting a correlation between successful PEG-fusion and both motor-dominant and sensory-dominant behavioral recoveries.This correlation was independent of the sex or strain of the rat.Furthermore,our data showed that the acceleration of von Frey filament sensory recovery to baseline was solely due to the PEG-fused sciatic nerve and not saphenous nerve collateral outgrowths.No chronic hypersensitivity developed in any rat up to 12 weeks.All these data suggest that PEG-fusion repair of transection peripheral nerve injuries co uld have important clinical benefits.
基金supported by Yunnan Province Innovation Team of Prevention and Treatment for Brain Disease with Acupuncture and Tuina,No.202405AS350007Youth Top Talent Project of 10-thousand Talent Plan in Yunnan Province,No.YNWR-QNBJ-2018-345+3 种基金the National Natural Science Foundation of China,No.81960731Joint Special Project of Traditional Chinese Medicine in Science and Technology Department of Yunnan Province,Nos.2019FF002[-008],202001AZ070001-002 and 202001AZ070001-030Yunnan Province University Innovation Team Projects No.2019YGC04Yunnan Province Project Education Fund,Nos.2024Y406,2024Y414(all to PZ)。
文摘The exchange of information and materials between organelles plays a crucial role in regulating cellular physiological functions and metabolic levels.Mitochondria-associated endoplasmic reticulum membranes serve as physical contact channels between the endoplasmic reticulum membrane and the mitochondrial outer membrane,formed by various proteins and protein complexes.This microstructural domain mediates several specialized functions,including calcium(Ca^(2+))signaling,autophagy,mitochondrial morphology,oxidative stress response,and apoptosis.Notably,the dysregulation of Ca^(2+)signaling mediated by mitochondria-associated endoplasmic reticulum membranes is a critical factor in the pathogenesis of neurological diseases.Certain proteins or protein complexes within these membranes directly or indirectly regulate the distance between the endoplasmic reticulum and mitochondria,as well as the transduction of Ca^(2+)signaling.Conversely,Ca^(2+)signaling mediated by mitochondria-associated endoplasmic reticulum membranes influences other mitochondria-associated endoplasmic reticulum membraneassociated functions.These functions can vary significantly across different neurological diseases—such as ischemic stroke,traumatic brain injury,Alzheimer's disease,Parkinson's disease,amyotrophic lateral sclerosis,and Huntington's disease—and their respective stages of progression.Targeted modulation of these disease-related pathways and functional proteins can enhance neurological function and promote the regeneration and repair of damaged neurons.Therefore,mitochondria-associated endoplasmic reticulum membranes-mediated Ca^(2+)signaling plays a pivotal role in the pathological progression of neurological diseases and represents a significant potential therapeutic target.This review focuses on the effects of protein complexes in mitochondria-associated endoplasmic reticulum membranes and the distinct roles of mitochondria-associated endoplasmic reticulum membranes-mediated Ca^(2+)signaling in neurological diseases,specifically highlighting the early protective effects and neuronal damage that can result from prolonged mitochondrial Ca^(2+)overload or deficiency.This article provides a comprehensive analysis of the various mechanisms of Ca^(2+)signaling mediated by mitochondria-associated endoplasmic reticulum membranes in neurological diseases,contributing to the exploration of potential therapeutic targets for promoting neuroprotection and nerve repair.
基金Science and Technology Planning Project of Inner Mongolia Science and Technology Department(2022YFSH0021)Key Research and Development Program of Shaanxi Province(2024SF2-GJHX-14,2021SF-296)。
文摘Four types of Mg-5Zn porous scaffolds with different pore geometries,including body-centered cubic(bcc),the rhombic dodecahedron(RD),gyroid(G),and primitive(P)types,were designed and fabricated using selective laser melting.Their forming quality,compression mechanical properties,and degradation behavior were investigated.Results indicate that the fabricated scaffolds exhibit good dimensional accuracy,and the surface chemical polishing treatment significantly improves the forming quality and reduces porosity error in porous scaffolds.Compared to the ones with rod structures(bcc,RD),the scaffolds with surface structures(G,P)have less powder particle adhesion.The G porous scaffold exhibits the best forming quality for the same design porosity.The predominant failure mode of scaffolds during compression is a 45°shear fracture.At a porosity of 75%,the compression property of all scaffolds meets the compressive property requirements of cancellous bone,while bcc and G structures show relatively better compression property.After immersion in Hank's solution for 168 h,the B-2-75% pore structure scaffold exhibits severe localized corrosion,with fractures in partial pillar connections.In contrast,the G-3-75% pore structure scaffold mainly undergoes uniform corrosion,maintaining structural integrity,and its corrosion rate and loss of compressive properties are less than those of the B-2-75%structure.After comparison,the G-pore structure scaffold is preferred.
文摘Background:Flexor tendon injuries in zones II–V are challenging because of the risk of adhesions and rupture.Although early passive mobilization limits rupture,it often compromises the functional recovery.Recent approaches favor early active mobilization with strong,multi-stranded core sutures to enhance outcomes.This study evaluated early active mobilization after eight-strand core repair in a tertiary care setting.Methods:In this prospective study,143 tendons from 30 patients who underwent surgery were followed up.The injured tendons were repaired using an eight-strand cross-locked cruciate technique with a double-stranded 4-0 suture,providing the tensile strength of eight strands with the same number of suture passes as in traditional four-core repairs,thereby reducing operative time without increasing bulk.Early active mobilization was initiated on postoperative day 2.The patients underwent digitally supervised physiotherapy and were monitored using a dedicated WhatsApp group,which enabled real-time guidance and compliance monitoring.The outcomes were measured in terms of total active motion,grip strength,pinch strength,time to return to work,postoperative pain,and complications.Results:Of the 30 patients,28(93.3%)had fair-to-excellent outcomes,whereas only 2(6.7%)had poor outcomes.Most patients(93.3%)returned to work within 12 weeks postoperatively.Four(13.3%)patients had complications,such as wound infection and skin necrosis.The patients showed significant changes in grip strength(45.2%)and pinch strength(70.7%)between weeks 8 and 12.No tendon ruptures were observed.Conclusion:The eight-core suturing technique used for flexor tendon repair withstood the forces of early active mobilization,which began on the second day after surgery,resulting in fair-to-excellent outcomes.It supports digitally supervised physiotherapy through app-based monitoring,enhancing patient compliance,and reducing reliance on in-person therapy sessions.This combination led to excellent functional recovery with minimal complications.
文摘BACKGROUND Descending thoracic aortic aneurysms are dangerous and have to be treated quickly.The primary treatment methods are thoracic endovascular aortic repair(TEVAR)and open surgical repair(OSR).The comparative effectiveness and safety of TEVAR and OSR were evaluated in this meta-analysis,focusing on perioperative and long-term outcomes.AIM To compare and contrast the efficacy and safety of TEVAR vs OSR in the treatment of descending thoracic aortic aneurysms.This study aims to assess both perioperative and long-term outcomes through a systematic review and metaanalysis.METHODS A comprehensive search of PubMed,EMBASE,and Cochrane was conducted from inception to January 2025.Baseline characteristics and outcomes were evaluated.Odds ratios(OR)for dichotomous data and mean differences for continuous data with 95%confidence intervals(CI)were analyzed using random-effects models.RESULTS A meta-analysis of 21 studies involving 29465 patients(8261 TEVAR;21204 OR)showed TEVAR associated with lower operative mortality(OR=0.60,95%CI:0.42-0.85,P=0.004),shorter intensive care unit(-2.94 days,95%CI:-4.76 to-1.12,P=0.002)and hospital stays(-7.35 days,95%CI:-10.54 to-4.17,P<0.00001),and reduced rates of paraplegia(OR=0.44,95%CI:0.27-0.73,P=0.002),spinal ischemia(OR=0.30,95%CI:0.16-0.56,P=0.0002),renal failure(OR=0.29,95%CI:0.14-0.61,P=0.001),and wound infections(OR=0.28,95%CI:0.13-0.61,P=0.001).However,TEVAR had higher rates of vascular complications.No significant differences were noted in 1-year and 5-year mortality rates,the rate of non-elective surgery,neurological complications,or stroke rates.CONCLUSION Compared to EVAR,TEVAR revealed lower operative mortality and better perioperative outcomes across all indicators,including hospital and intensive care unit stays,as well as fewer complications,except for those related to vascular problems.Mortality results were also similar in the long run;consequently,more research is required concerning the long-term durability.
