Introduction: Carpal tunnel syndrome is a more common form of upper limb canal syndrome, resulting from compression of the median nerve in the carpal tunnel, but is particularly troublesome. Medical treatment is often...Introduction: Carpal tunnel syndrome is a more common form of upper limb canal syndrome, resulting from compression of the median nerve in the carpal tunnel, but is particularly troublesome. Medical treatment is often unsuccessful, and surgical treatment usually involves transection of the annular ligament. The aim of this study was to assess iatrogenic intraoperative and postoperative complications, as well as patient outcomes following the use of conventional and endoscopic surgery in the surgical management of carpal tunnel syndrome. Hypothesis: Are nerve, vascular and tendon injuries of iatrogenic origin always present in the surgical management of carpal tunnel syndrome, even though this surgery is performed on an outpatient basis? Patients and methods: This retrospective series is composed of 1140 patients, 230 men and 910 women, mean age 58.6 ± 16.4 years, operated on between 2010 and 2020 for carpal tunnel syndrome by conventional surgery and under endoscopy. Medical records, operative reports and consultation letters were consulted. All patients were reviewed regularly at one month post-op until recovery. Results: No nerve, vascular or tendon damage was noted, and at a maximum follow-up of 2 years, 20 patients had recurred, i.e. a 2.51% failure rate. Scar disunion was observed in 0.9%, wound infection in 0.9% and scar fibrosis in 0.9%. 92.98% of patients underwent outpatient surgery, irrespective of the type of anesthesia or surgical technique used. Patients who stayed in hospital for a short time were suffering from carpal tunnel syndrome associated with compression of the ulnar nerve in Guyon’s canal, for which both the median and ulnar nerves were freed during the same operation, under general anaesthetic. All patients were able to return to their previous activity within 30 days of surgery. Conclusion: Intraoperative iatrogenic complications, notably nerve, vascular and tendon lesions, were not identified despite the large sample size. On the other hand, postoperative skin complications related to scarring, such as wound disunion, fibrosis and recurrence, were present despite low rates.展开更多
Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death.China has the largest population of patients with traumatic spinal cord injury.Previous studies of traumatic ...Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death.China has the largest population of patients with traumatic spinal cord injury.Previous studies of traumatic spinal cord injury in China have mostly been regional in scope;national-level studies have been rare.To the best of our knowledge,no national-level study of treatment status and economic burden has been performed.This retrospective study aimed to examine the epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China at the national level.We included 13,465 traumatic spinal cord injury patients who were injured between January 2013 and December 2018 and treated in 30 hospitals in 11 provinces/municipalities representing all geographical divisions of China.Patient epidemiological and clinical features,treatment status,and total and daily costs were recorded.Trends in the percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department and cost of care were assessed by annual percentage change using the Joinpoint Regression Program.The percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department did not significantly change overall(annual percentage change,-0.5%and 2.1%,respectively).A total of 10,053(74.7%)patients underwent surgery.Only 2.8%of patients who underwent surgery did so within 24 hours of injury.A total of 2005(14.9%)patients were treated with high-dose(≥500 mg)methylprednisolone sodium succinate/methylprednisolone(MPSS/MP);615(4.6%)received it within 8 hours.The total cost for acute traumatic spinal cord injury decreased over the study period(-4.7%),while daily cost did not significantly change(1.0%increase).Our findings indicate that public health initiatives should aim at improving hospitals’ability to complete early surgery within 24 hours,which is associated with improved sensorimotor recovery,increasing the awareness rate of clinical guidelines related to high-dose MPSS/MP to reduce the use of the treatment with insufficient evidence.展开更多
Osteoarthritis(OA)is a common degenerative disease worldwide and new therapeutics that target inflammation and the crosstalk between immunocytes and chondrocytes are being developed to prevent and treat OA.These attem...Osteoarthritis(OA)is a common degenerative disease worldwide and new therapeutics that target inflammation and the crosstalk between immunocytes and chondrocytes are being developed to prevent and treat OA.These attempts involve repolarizing pro-inflammatory M1 macrophages into the anti-inflammatory M2 phenotype in synovium.In this study,we found that phosphoglycerate mutase 5(PGAM5)significantly increased in macrophages in OA synovium compared to controls based on histology of human samples and single-cell RNA sequencing results of mice models.To address the role of PGAM5 in macrophages in OA,we found conditional knockout of PGAM5 in macrophages greatly alleviated OA symptoms and promoted anabolic metabolism of chondrocytes in vitro and in vivo.Mechanistically,we found that PGAM5 enhanced M1 polarization via AKT-mTOR/p38/ERK pathways,whereas inhibited M2 polarization via STAT6-PPARγpathway in murine bone marrow-derived macrophages.Furthermore,we found that PGAM5 directly dephosphorylated Dishevelled Segment Polarity Protein 2(DVL2)which resulted in the inhibition ofβ-catenin and repolarization of M2 macrophages into M1 macrophages.Conditional knockout of both PGAM5 andβ-catenin in macrophages significantly exacerbated osteoarthritis compared to PGAM5-deficient mice.Motivated by these findings,we successfully designed mannose modified fluoropolymers combined with siPGAM5 to inhibit PGAM5 specifically in synovial macrophages via intra-articular injection,which possessed desired targeting abilities of synovial macrophages and greatly attenuated murine osteoarthritis.Collectively,these findings defined a key role for PGAM5 in orchestrating macrophage polarization and provides insights into novel macrophage-targeted strategy for treating OA.展开更多
BACKGROUND While Singapore attains good health outcomes,Singapore’s healthcare system is confronted with bed shortages and prolonged stays for elderly people recovering from surgery in acute hospitals.An Acute Hospit...BACKGROUND While Singapore attains good health outcomes,Singapore’s healthcare system is confronted with bed shortages and prolonged stays for elderly people recovering from surgery in acute hospitals.An Acute Hospital-Community Hospital(AHCH)care bundle has been developed to assist patients in postoperative rehabilitation.The core concept is to transfer patients out of AHs when clinically recommended and into CHs,where they can receive more beneficial dedicated care to aid in their recovery,while freeing up bed capacities in AHs.AIM To analyze the AH length of stay(LOS),costs,and savings associated with the AH-CH care bundle intervention initiated and implemented in elderly patients aged 75 years and above undergoing elective orthopedic surgery.METHODS A total of 8621:1 propensity score-matched patients aged 75 years and above who underwent elective orthopedic surgery in Singapore General Hospital(SGH)before(2017-2018)and after(2019-2021)the care bundle intervention period was analyzed.Outcome measures were AH LOS,CH LOS,hospitalization metrics,postoperative 30-d mortality,and modified Barthel Index(MBI)scores.The costs of AH inpatient hospital stay in the matched cohorts were compared using cost data in Singapore dollars.RESULTS Of the 862 matched elderly patients undergoing elective orthopedic surgery before and after the care bundle intervention,the age distribution,sex,American Society of Anesthesiologists classification,Charlson Comorbidity Index,and surgical approach were comparable between both groups.Patients transferred to CHs after the surgery had a shorter median AH LOS(7 d vs 9 d,P<0.001).The mean total AH inpatient cost per patient was 14.9%less for the elderly group transferred to CHs(S$24497.3 vs S$28772.8,P<0.001).The overall AH U-turn rates for elderly patients within the care bundle were low,with a 0%mortality rate following orthopedic surgery.When elderly patients were discharged from CHs,their MBI scores increased significantly(50.9 vs 71.9,P<0.001).CONCLUSION The AH-CH care bundle initiated and implemented in the Department of Orthopedic Surgery appears to be effective and cost-saving for SGH.Our results indicate that transitioning care between acute and community hospitals using this care bundle effectively reduces AH LOS in elderly patients receiving orthopedic surgery.Collaboration between acute and community care providers can assist in closing the care delivery gap and enhancing service quality.展开更多
Rarely,penetrating injuries to the spinal cord result from wooden objects,creating unique challenges to mitigate neurological injury and high rates of infection and foreign body reactions.We report a man who sustained...Rarely,penetrating injuries to the spinal cord result from wooden objects,creating unique challenges to mitigate neurological injury and high rates of infection and foreign body reactions.We report a man who sustained a penetrating cervical spinal cord injury from a sharpened stick.While initially tetraparetic,he rapidly recovered function.The risks of neurological deterioration during surgical removal made the patient reluctant to consent to surgery despite the impalement of the spinal cord.A repeat MRI on day 3 showed an extension of edema indicating progressive inflammation.On the 7~(th)day after injury,fever and paresthesias occurred with a large increase in serum inflammatory indicators,and the patient agreed to undergo surgical removal of the wooden object.We discuss the management nuances related to wood,the longitudinal evolution of MRI findings,infection risk,surgical risk mitigation and technique,an inflammatory marker profile,long-term recovery,and the surprisingly minimal neurological deficits associated with low-velocity midline spinal cord injuries.The patient had an excellent clinical outcome.The main lessons are that a wooden penetrating central nervous system injury has a high risk for infection,and that surgical removal from the spinal cord should be performed soon after injury and under direct visualization.展开更多
BACKGROUND East Asia is the most dynamic region in the world and includes three major countries:Japan,South Korea and China.Due to rapid economic growth,orthopedics research in East Asia has achieved great advances du...BACKGROUND East Asia is the most dynamic region in the world and includes three major countries:Japan,South Korea and China.Due to rapid economic growth,orthopedics research in East Asia has achieved great advances during the past 10 years.However,the current status of orthopedic research in Japan,South Korea and China is still unclear.AIM To understand the current status of orthopedic research in Japan,South Korea,and China.METHODS Journals listed in the“Orthopedics”category of Science Citation Index Expanded subject categories were included.The PubMed and Web of Knowledge electronic databases were searched to identify scientific publications from the selected journals written by researchers from Japan,South Korea and China.A systematic analysis was conducted to analyze orthopedic research articles published in the three countries based on the number of articles,study design,impact factors(IFs)and citations.Furthermore,we also ranked the top 10 countries worldwide with the highest publications in the past 10 years.Additionally,we ranked the top 10 countries with the highest number of publications in the world in the past 10 years.Statistical analyses were performed using SPSS 20.0 software(SPSS Inc.,Chicago,IL,United States),and statistical results are given in Tables and Figures.The Kruskal-Wallis test and the Mann-Whitney test were used to detect differences between countries.The tendency regarding the number of articles was analyzed by curvilinear regression.A two-tailed P<0.05 was considered significant.RESULTS From 2012-2021,a total of 144518 articles were published in the 86 selected orthopedic journals.During this period,the number of worldwide published orthopedic articles has shown an annual increasing trend.A total of 27164 orthopedic research articles were published by Japan,South Korea and China during the past 10 years;44.32%were from China,32.98%were from Japan,and 22.70%were from South Korea.From 2012 to 2021,the annual number of articles markedly increased in each of the three countries.Over time,the worldwide share of articles increased substantially in South Korea(3.37%to 6.53%,P<0.001)and China(5.29%to 9.61%,P<0.001).However,the worldwide share of articles significantly decreased in Japan(5.22%to 3.80%,P<0.001).The annual total IFs of articles from China were well above those of articles from Japan and South Korea(36597.69 vs 27244.48 vs 20657.83,P<0.05).There was no significant difference among the articles in the top 10 high-IF orthopedics journals published from those three countries[South Korea(800)>China(787)>Japan(646),P>0.05].CONCLUSION Over the past 10 years,China’s scientific publications in orthopedic journals have shown an increasing trend.Considering the relative scale of the populations,Japan and South Korea have outpaced China with respect to quality.展开更多
Purpose: Implant subsidence is a possible complication of spinal interbody fusion. We aim to evaluate porous titanium cages subsidence, fusion and functional outcomes in patients subjected to oblique lumbar interbody ...Purpose: Implant subsidence is a possible complication of spinal interbody fusion. We aim to evaluate porous titanium cages subsidence, fusion and functional outcomes in patients subjected to oblique lumbar interbody fusion (OLIF) with these novel devices. Methods: Our institutional review board approved a single-center experience which included 60 patients who underwent OLIF from June 2018 to June 2020 utilizing the porous titanium implants. Data was collected in accordance with the Declaration of Helsinki, and written informed consent was obtained. Imaging studies including radiographs 1, 3, 6 and 12 months and computed tomography (CT) scan at 6 months obtained during routine postoperative follow-up visits, were studied for signs of implant subsidence, fusion and clinical parameters to determine the effectiveness of surgery such as Oswestry disability index (ODI). Results: Radiographic subsidence occurred in 1 out of 89 porous titanium interbody cages (1.1%). No subsidence was observed in the posterior screws and rods fixation group (N = 57). However, one case of subsidence occurred in the lateral plate fixation group (N = 3). The subsidence occurred in an osteoporotic elderly patient operated for adjacent segment disease, and she was later revised with posterior instrumentation using cemented screws and rods. She had an uneventful recovery. Fusion rates were evaluated under CT scan at 6 months with a rate of 88%. In terms of clinical outcomes, ODI decreased significantly from 20.3 preop to 10.7 postop with a P-value Conclusions: In our study, the subsidence rate was lower than previously reported in the literature. Also, we had good fusion rates at 6 months likely due to the porous titanium cages use. We had no subsidence in the posterior instrumented group and one case in the lateral fixation group with improved clinical outcomes.展开更多
Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely studied.However,their inability to cross the blood–brain barrier hampers the clinical translation of these...Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely studied.However,their inability to cross the blood–brain barrier hampers the clinical translation of these therapeutic strategies.Liposomes are nanoparticles composed of lipid bilayers,which can effectively encapsulate drugs and improve drug delivery across the blood–brain barrier and into brain tissue through their targeting and permeability.Therefore,they can potentially treat traumatic and nontraumatic central nervous system diseases.In this review,we outlined the common properties and preparation methods of liposomes,including thin-film hydration,reverse-phase evaporation,solvent injection techniques,detergent removal methods,and microfluidics techniques.Afterwards,we comprehensively discussed the current applications of liposomes in central nervous system diseases,such as Alzheimer's disease,Parkinson's disease,Huntington's disease,amyotrophic lateral sclerosis,traumatic brain injury,spinal cord injury,and brain tumors.Most studies related to liposomes are still in the laboratory stage and have not yet entered clinical trials.Additionally,their application as drug delivery systems in clinical practice faces challenges such as drug stability,targeting efficiency,and safety.Therefore,we proposed development strategies related to liposomes to further promote their development in neurological disease research.展开更多
Spinal cord injuries lead to significant loss of motor, sensory, and autonomic functions, presenting major challenges in neural regeneration. Achieving effective therapeutic concentrations at injury sites has been a s...Spinal cord injuries lead to significant loss of motor, sensory, and autonomic functions, presenting major challenges in neural regeneration. Achieving effective therapeutic concentrations at injury sites has been a slow process, partly due to the difficulty of delivering drugs effectively. Nanoparticles, with their targeted delivery capabilities, biocompatibility, and enhanced bioavailability over conventional drugs, are garnering attention for spinal cord injury treatment. This review explores the current mechanisms and shortcomings of existing treatments, highlighting the benefits and progress of nanoparticle-based approaches. We detail nanoparticle delivery methods for spinal cord injury, including local and intravenous injections, oral delivery, and biomaterial-assisted implantation, alongside strategies such as drug loading and surface modification. The discussion extends to how nanoparticles aid in reducing oxidative stress, dampening inflammation, fostering neural regeneration, and promoting angiogenesis. We summarize the use of various types of nanoparticles for treating spinal cord injuries, including metallic, polymeric, protein-based, inorganic non-metallic, and lipid nanoparticles. We also discuss the challenges faced, such as biosafety, effectiveness in humans, precise dosage control, standardization of production and characterization, immune responses, and targeted delivery in vivo. Additionally, we explore future directions, such as improving biosafety, standardizing manufacturing and characterization processes, and advancing human trials. Nanoparticles have shown considerable progress in targeted delivery and enhancing treatment efficacy for spinal cord injuries, presenting significant potential for clinical use and drug development.展开更多
BACKGROUND:Adeno-associated virus(AAV)gene therapy has been proven to be reliable and safe for the treatment of osteoarthritis in recent years.However,given the complexity of osteoarthritis pathogenesis,single gene ma...BACKGROUND:Adeno-associated virus(AAV)gene therapy has been proven to be reliable and safe for the treatment of osteoarthritis in recent years.However,given the complexity of osteoarthritis pathogenesis,single gene manipulation for the treatment of osteoarthritis may not produce satisfactory results.Previous studies have shown that nuclear factorκB could promote the inflammatory pathway in osteoarthritic chondrocytes,and bone morphogenetic protein 4(BMP4)could promote cartilage regeneration.OBJECTIVE:To test whether combined application of AAV-p65shRNA and AAV-BMP4 will yield the synergistic effect on chondrocytes regeneration and osteoarthritis treatment.METHODS:Viral particles containing AAV-p65-shRNA and AAV-BMP4 were prepared.Their efficacy in inhibiting inflammation in chondrocytes and promoting chondrogenesis was assessed in vitro and in vivo by transfecting AAV-p65-shRNA or AAV-BMP4 into cells.The experiments were divided into five groups:PBS group;osteoarthritis group;AAV-BMP4 group;AAV-p65shRNA group;and BMP4-p65shRNA 1:1 group.Samples were collected at 4,12,and 24 weeks postoperatively.Tissue staining,including safranin O and Alcian blue,was applied after collecting articular tissue.Then,the optimal ratio between the two types of transfected viral particles was further investigated to improve the chondrogenic potential of mixed cells in vivo.RESULTS AND CONCLUSION:The combined application of AAV-p65shRNA and AAV-BMP4 together showed a synergistic effect on cartilage regeneration and osteoarthritis treatment.Mixed cells transfected with AAV-p65shRNA and AAV-BMP4 at a 1:1 ratio produced the most extracellular matrix synthesis(P<0.05).In vivo results also revealed that the combination of the two viruses had the highest regenerative potential for osteoarthritic cartilage(P<0.05).In the present study,we also discovered that the combined therapy had the maximum effect when the two viruses were administered in equal proportions.Decreasing either p65shRNA or BMP4 transfected cells resulted in less collagen II synthesis.This implies that inhibiting inflammation by p65shRNA and promoting regeneration by BMP4 are equally important for osteoarthritis treatment.These findings provide a new strategy for the treatment of early osteoarthritis by simultaneously inhibiting cartilage inflammation and promoting cartilage repair.展开更多
In clinical practice,cervical spine surgery inevitably alters the original physiological structure of the cervical spine,thus causing changes in the original biomechanical properties of the cervical spine.The biomecha...In clinical practice,cervical spine surgery inevitably alters the original physiological structure of the cervical spine,thus causing changes in the original biomechanical properties of the cervical spine.The biomechanical properties of the cervical spine are particularly significant as it is an essential structure that supports the head and connects the trunk.Different cervical spine surgery options can have different effects on the biomechanics of the cervical spine.Therefore,this review will discuss recent research advances on the effects of cervical spine surgery on cervical spine biomechanics.We hope that this review will provide some theoretical basis for future studies on the biomechanical effects of cervical spine surgery on the cervical spine.展开更多
Bone is a mechanosensitive tissue and undergoes constant remodeling to adapt to the mechanical loading environment.However,it is unclear whether the signals of bone cells in response to mechanical stress are processed...Bone is a mechanosensitive tissue and undergoes constant remodeling to adapt to the mechanical loading environment.However,it is unclear whether the signals of bone cells in response to mechanical stress are processed and interpreted in the brain.In this study,we found that the hypothalamus of the brain regulates bone remodeling and structure by perceiving bone prostaglandin E2(PGE2)concentration in response to mechanical loading.Bone PGE2 levels are in proportion to their weight bearing.When weight bearing changes in the tail-suspension mice,the PGE2 concentrations in bones change in line with their weight bearing changes.Deletion of cyclooxygenase-2(COX2)in the osteoblast lineage cells or knockout of receptor 4(EP4)in sensory nerve blunts bone formation in response to mechanical loading.Moreover,knockout of TrkA in sensory nerve also significantly reduces mechanical load-induced bone formation.Moreover,mechanical loading induces cAMP-response element binding protein(CREB)phosphorylation in the hypothalamic arcuate nucleus(ARC)to inhibit sympathetic tyrosine hydroxylase(TH)expression in the paraventricular nucleus(PVN)for osteogenesis.Finally,we show that elevated PGE2 is associated with ankle osteoarthritis(AOA)and pain.Together,our data demonstrate that in response to mechanical loading,skeletal interoception occurs in the form of hypothalamic processing of PGE2-driven peripheral signaling to maintain physiologic bone homeostasis,while chronically elevated PGE2 can be sensed as pain during AOA and implication of potential treatment.展开更多
BACKGROUND Simple bone cysts(SBC)are benign tumor-like bone lesions typically identified in children.While SBC may lead to growth disturbances or growth arrest,such cases are uncommon.The mechanisms behind these obser...BACKGROUND Simple bone cysts(SBC)are benign tumor-like bone lesions typically identified in children.While SBC may lead to growth disturbances or growth arrest,such cases are uncommon.The mechanisms behind these observations remain unclear.Additionally,research on the etiology of SBC remains inconclusive,and there has been no consensus on the appropriate timing and methodology for treatment.CASE SUMMARY Here,we present our experience in the successful surgical management of a 10-year-old girl with SBC,who presented with a pathological fracture complicated by malunion of the displaced fracture,varus deformity,and limb length discrepancy.We hypothesized two possible etiologies for the patient’s growth arrest and subsequent humerus varus deformity:(1)Direct disruption of the physis by fluid from the cyst itself;and(2)damage to the epiphysis due to repetitive pathological fractures associated with SBC.In addressing this case,surgical intervention was undertaken to correct the proximal humerus varus deformity.This approach offered the advantages of simultaneously correcting angular abnormalities,achieving mild limb lengthening,providing definitive SBC treatment,and reducing the overall treatment duration.CONCLUSION As per current literature,acute correction of acute angular deformity in proximal humeral SBC is not well comprehended.However,in this specific case,acute correction was considered an optimal solution.展开更多
Peripheral nerve injury(PNI)is a common neurological disorder and complete functional recovery is difficult to achieve.In recent years,bone marrow mesenchymal stem cells(BMSCs)have emerged as ideal seed cells for PNI ...Peripheral nerve injury(PNI)is a common neurological disorder and complete functional recovery is difficult to achieve.In recent years,bone marrow mesenchymal stem cells(BMSCs)have emerged as ideal seed cells for PNI treatment due to their strong differentiation potential and autologous trans-plantation ability.This review aims to summarize the molecular mechanisms by which BMSCs mediate nerve repair in PNI.The key mechanisms discussed include the differentiation of BMSCs into multiple types of nerve cells to promote repair of nerve injury.BMSCs also create a microenvironment suitable for neuronal survival and regeneration through the secretion of neurotrophic factors,extracellular matrix molecules,and adhesion molecules.Additionally,BMSCs release pro-angiogenic factors to promote the formation of new blood vessels.They modulate cytokine expression and regulate macrophage polarization,leading to immunomodulation.Furthermore,BMSCs synthesize and release proteins related to myelin sheath formation and axonal regeneration,thereby promoting neuronal repair and regeneration.Moreover,this review explores methods of applying BMSCs in PNI treatment,including direct cell trans-plantation into the injured neural tissue,implantation of BMSCs into nerve conduits providing support,and the application of genetically modified BMSCs,among others.These findings confirm the potential of BMSCs in treating PNI.However,with the development of this field,it is crucial to address issues related to BMSC therapy,including establishing standards for extracting,identifying,and cultivating BMSCs,as well as selecting application methods for BMSCs in PNI such as direct transplantation,tissue engineering,and genetic engineering.Addressing these issues will help translate current preclinical research results into clinical practice,providing new and effective treatment strategies for patients with PNI.展开更多
BACKGROUND The pedicle screw technique is widely employed for vertebral body fixation in the treatment of spinal disorders.However,traditional screw placement methods require the dissection of paraspinal muscles and t...BACKGROUND The pedicle screw technique is widely employed for vertebral body fixation in the treatment of spinal disorders.However,traditional screw placement methods require the dissection of paraspinal muscles and the insertion of pedicle screws at specific transverse section angles(TSA).Larger TSA angles require more force to pull the muscle tissue,which can increase the risk of surgical trauma and ischemic injury to the lumbar muscles.AIM To study the feasibility of zero-degree TSA vertical pedicle screw technique in the lumbosacral segment.METHODS Finite element models of vertebral bodies and pedicle screw-rod systems were established for the L4-S1 spinal segments.A standard axial load of 500 N and a rotational torque of 10 N/m were applied.Simulated screw pull-out experiment was conducted to observe pedicle screw resistance to pull-out,maximum stress,load-displacement ratio,maximum stress in vertebral bodies,load-displacement ratio in vertebral bodies,and the stress distribution in pedicle screws and vertebral bodies.Differences between the 0-degree and 17-degree TSA were compared.RESULTS At 0-degree TSA,the screw pull-out force decreased by 11.35%compared to that at 17-degree TSA(P<0.05).At 0-degree and 17-degree TSA,the stress range in the screw-rod system was 335.1-657.5 MPa and 242.8-648.5 MPa,separately,which were below the fracture threshold for the screw-rod system(924 MPa).At 0-degree and 17-degree TSA,the stress range in the vertebral bodies was 68.45-78.91 MPa and 39.08-72.73 MPa,separately,which were below the typical bone yield stress range for vertebral bodies(110-125 MPa).At 0-degree TSA,the load-displacement ratio for the vertebral bodies and pedicle screws was slightly lower compared to that at 17-degree TSA,indicating slightly lower stability(P<0.05).CONCLUSION The safety and stability of 0-degree TSA are slightly lower,but the risks of screw-rod system fracture,vertebral body fracture,and rupture are within acceptable limits.展开更多
BACKGROUND Advances in implant material and design have allowed for improvements in total knee arthroplasty(TKA)outcomes.A cruciate retaining(CR)TKA provides the least constraint of TKA designs by preserving the nativ...BACKGROUND Advances in implant material and design have allowed for improvements in total knee arthroplasty(TKA)outcomes.A cruciate retaining(CR)TKA provides the least constraint of TKA designs by preserving the native posterior cruciate ligament.Limited research exists that has examined clinical outcomes or patient reported outcome measures(PROMs)of a large cohort of patients undergoing a CR TKA utilizing a kinematically designed implant.It was hypothesized that the studied CR Knee System would demonstrate favorable outcomes and a clinically significant improvement in pain and functional scores.AIM To assess both short-term and mid-term clinical outcomes and PROMs of a novel CR TKA design.METHODS A retrospective,multi-surgeon study identified 255 knees undergoing a TKA utilizing a kinematically designed CR Knee System(JOURNEY™II CR;Smith and Nephew,Inc.,Memphis,TN)at an urban,academic medical institution between March 2015 and July 2021 with a minimum of two-years of clinical follow-up with an orthopedic surgeon.Patient demographics,surgical information,clinical outcomes,and PROMs data were collected via query of electronic medical records.The PROMs collected in the present study included the Knee Injury and Osteoarthritis Outcome Score for Joint Replacement(KOOS JR)and Patient-Reported Outcomes Measurement Information System(PROMIS■)scores.The significance of improvements in mean PROM scores from preoperative scores to scores collected at six months and two-years postoperatively was analyzed using Independent Samples t-tests.RESULTS Of the 255 patients,65.5%were female,43.8%were White,and patients had an average age of 60.6 years.Primary osteoarthritis(96.9%)was the most common primary diagnosis.The mean surgical time was 105.3 minutes and mean length of stay was 2.1 d with most patients discharged home(92.5%).There were 18 emergency department(ED)visits within 90 d of surgery resulting in a 90 d ED visit rate of 7.1%,including a 2.4%orthopedic-related ED visit rate and a 4.7%non-orthopedic-related ED visit rate.There were three(1.2%)hospital readmissions within 90 d postoperatively.With a mean time to latest follow-up of 3.3 years,four patients(1.6%)required revision,two for arthrofibrosis,one for aseptic femoral loosening,and one for peri-prosthetic joint infection.There were significant improvements in KOOS JR,PROMIS Pain Intensity,PROMIS Pain Interference,PROMIS Mobility,and PROMIS Physical Health from preoperative scores to six month and two-year postoperative scores.CONCLUSION The evaluated implant is an effective,novel design offering excellent outcomes and low complication rates.At a mean follow up of 3.3 years,four patients required revisions,three aseptic and one septic,resulting in an overall implant survival rate of 98.4%and an aseptic survival rate of 98.8%.The results of our study demonstrate the utility of this kinematically designed implant in the setting of primary TKA.展开更多
BACKGROUND Congenital absence of the menisci is a rare anatomical variation characterized by the absence or underdevelopment of one or both menisci in the knee joint.The menisci are crucial in load distribution,joint ...BACKGROUND Congenital absence of the menisci is a rare anatomical variation characterized by the absence or underdevelopment of one or both menisci in the knee joint.The menisci are crucial in load distribution,joint stability,and shock absorption.Understanding the clinical presentation,diagnosis,and management of this condition is important for optimal patient care.CASE SUMMARY A 27-year-old male with a long-standing history of knee pain underwent diagnostic arthroscopy,revealing a congenital absence of the meniscus.The patient's clinical findings,imaging results,surgical procedures,and pertinent images are detailed.This case presents a unique aspect with the congenital absence of the meniscus,contributing valuable insights to the literature on rare anatomical anomalies.CONCLUSION This case of congenital absence of the menisci highlights the diagnostic challenges posed by rare anomalies.The diagnostic arthroscopy played a crucial role in identifying the absence of the meniscus and providing an explanation for the patient's persistent knee pain.The case underscores the importance of individualized treatment approaches,including physical therapy,for optimal management of rare meniscal anomalies.Further research is warranted to explore effective management strategies for the aforementioned cases and to expand our knowledge of these rare conditions.展开更多
Rheumatoid arthritis(RA)is a systemic autoimmune disease that is primarily manifested as synovitis and polyarticular opacity and typically leads to serious joint damage and irreversible disability,thus adversely affec...Rheumatoid arthritis(RA)is a systemic autoimmune disease that is primarily manifested as synovitis and polyarticular opacity and typically leads to serious joint damage and irreversible disability,thus adversely affecting locomotion ability and life quality.Consequently,good prognosis heavily relies on the early diagnosis and effective therapeutic monitoring of RA.Activatable fluorescent probes play vital roles in the detection and imaging of biomarkers for disease diagnosis and in vivo imaging.Herein,we review the fluorescent probes developed for the detection and imaging of RA biomarkers,namely reactive oxygen/nitrogen species(hypochlorous acid,peroxynitrite,hydroxyl radical,nitroxyl),pH,and cysteine,and address the related challenges and prospects to inspire the design of novel fluorescent probes and the improvement of their performance in RA studies.展开更多
BACKGROUND Diabetic foot(DMF)complications are common and are increasing in incidence.Risk factors related to wound complications are yet to be established after transtibial amputation under the diagnosis of DMF infec...BACKGROUND Diabetic foot(DMF)complications are common and are increasing in incidence.Risk factors related to wound complications are yet to be established after transtibial amputation under the diagnosis of DMF infection.AIM To analyze the prognosis and risk factors related to wound complications after transtibial amputation in patients with diabetes.METHODS This retrospective cohort study included seventy-two patients with DMF complications who underwent transtibial amputation between April 2014 and March 2023.The groups were categorized based on the occurrence of wound complications,and we compared demographic data between the complication group and the non-complication group to analyze risk factors.Moreover,a multivariate logistic regression analysis was performed to identify risk factors.RESULTS The average follow-up period was 36.2 months.Among the 72 cases,31(43.1%)had wound complications.Of these,12 cases(16.7%)received further treatment,such as debridement,soft tissue stump revision,and re-amputation at the proximal level.In a group that required further management due to wound complications after transtibial amputation,the hemoglobin A1c(HbA1c)level was 9.32,while the other group that did not require any treatment had a 7.54 HbA1c level.The prevalence of a history of kidney transplantation with wound complications after transtibial amputation surgery in DMF patients was significantly greater than in cases without wound complications(P=0.02).Other factors did not show significant differences.CONCLUSION Approximately 43.1%of the patients with transtibial amputation surgery experienced wound complications,and 16.7%required additional surgical treatment.High HbA1c levels and kidney transplant history are risk factors for postoperative wound complications.展开更多
Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural regeneration.The role of the small ubiqu...Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural regeneration.The role of the small ubiquitin-like modifier(SUMO)protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of SUMOylation.We used machine learning to create the exercise and SUMO-related gene signature(ESLRS).This signature shows how physical activity might help improve the outlook for low-grade glioma and other cancers.We demonstrated the prognostic and immunotherapeutic significance of ESLRS markers,specifically highlighting how murine double minute 2(MDM2),a component of the ESLRS,can be targeted by nutlin-3.This underscores the intricate relationship between natural compounds such as nutlin-3 and immune regulation.Using comprehensive CRISPR screening,we validated the effects of specific ESLRS genes on low-grade glioma progression.We also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic simulation.Nutlin-3a inhibited glioma cell proliferation and activated the p53 pathway.Its efficacy decreased with MDM2 overexpression,and this was reversed by Nutlin-3a or exercise.Experiments using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway regulation.Notably,both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing cells.These results suggest the potential for Nutlin-3a,an MDM2 inhibitor,with physical exercise as a therapeutic approach for glioma management.Our research also supports the use of natural products for therapy and sheds light on the interaction of exercise,natural products,and immune regulation in cancer treatment.展开更多
文摘Introduction: Carpal tunnel syndrome is a more common form of upper limb canal syndrome, resulting from compression of the median nerve in the carpal tunnel, but is particularly troublesome. Medical treatment is often unsuccessful, and surgical treatment usually involves transection of the annular ligament. The aim of this study was to assess iatrogenic intraoperative and postoperative complications, as well as patient outcomes following the use of conventional and endoscopic surgery in the surgical management of carpal tunnel syndrome. Hypothesis: Are nerve, vascular and tendon injuries of iatrogenic origin always present in the surgical management of carpal tunnel syndrome, even though this surgery is performed on an outpatient basis? Patients and methods: This retrospective series is composed of 1140 patients, 230 men and 910 women, mean age 58.6 ± 16.4 years, operated on between 2010 and 2020 for carpal tunnel syndrome by conventional surgery and under endoscopy. Medical records, operative reports and consultation letters were consulted. All patients were reviewed regularly at one month post-op until recovery. Results: No nerve, vascular or tendon damage was noted, and at a maximum follow-up of 2 years, 20 patients had recurred, i.e. a 2.51% failure rate. Scar disunion was observed in 0.9%, wound infection in 0.9% and scar fibrosis in 0.9%. 92.98% of patients underwent outpatient surgery, irrespective of the type of anesthesia or surgical technique used. Patients who stayed in hospital for a short time were suffering from carpal tunnel syndrome associated with compression of the ulnar nerve in Guyon’s canal, for which both the median and ulnar nerves were freed during the same operation, under general anaesthetic. All patients were able to return to their previous activity within 30 days of surgery. Conclusion: Intraoperative iatrogenic complications, notably nerve, vascular and tendon lesions, were not identified despite the large sample size. On the other hand, postoperative skin complications related to scarring, such as wound disunion, fibrosis and recurrence, were present despite low rates.
基金supported by the National Key Research and Development Project,No.2019YFA0112100(to SF).
文摘Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death.China has the largest population of patients with traumatic spinal cord injury.Previous studies of traumatic spinal cord injury in China have mostly been regional in scope;national-level studies have been rare.To the best of our knowledge,no national-level study of treatment status and economic burden has been performed.This retrospective study aimed to examine the epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China at the national level.We included 13,465 traumatic spinal cord injury patients who were injured between January 2013 and December 2018 and treated in 30 hospitals in 11 provinces/municipalities representing all geographical divisions of China.Patient epidemiological and clinical features,treatment status,and total and daily costs were recorded.Trends in the percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department and cost of care were assessed by annual percentage change using the Joinpoint Regression Program.The percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department did not significantly change overall(annual percentage change,-0.5%and 2.1%,respectively).A total of 10,053(74.7%)patients underwent surgery.Only 2.8%of patients who underwent surgery did so within 24 hours of injury.A total of 2005(14.9%)patients were treated with high-dose(≥500 mg)methylprednisolone sodium succinate/methylprednisolone(MPSS/MP);615(4.6%)received it within 8 hours.The total cost for acute traumatic spinal cord injury decreased over the study period(-4.7%),while daily cost did not significantly change(1.0%increase).Our findings indicate that public health initiatives should aim at improving hospitals’ability to complete early surgery within 24 hours,which is associated with improved sensorimotor recovery,increasing the awareness rate of clinical guidelines related to high-dose MPSS/MP to reduce the use of the treatment with insufficient evidence.
基金This work was supported by grants from National Natural Science Foundation of China(81830078,82071868,32370892)Science and Technology Commission of Shanghai Municipality(23141901200)+2 种基金Health Commission of Shanghai Municipality(2022JC029)Biomaterials and Regenerative Medicine Institute Cooperative Research Project,Shanghai Jiaotong University School of Medicine(2022LHA11)Shanghai Key Laboratory of Orthopedic Implant(No.KFKT202206).
文摘Osteoarthritis(OA)is a common degenerative disease worldwide and new therapeutics that target inflammation and the crosstalk between immunocytes and chondrocytes are being developed to prevent and treat OA.These attempts involve repolarizing pro-inflammatory M1 macrophages into the anti-inflammatory M2 phenotype in synovium.In this study,we found that phosphoglycerate mutase 5(PGAM5)significantly increased in macrophages in OA synovium compared to controls based on histology of human samples and single-cell RNA sequencing results of mice models.To address the role of PGAM5 in macrophages in OA,we found conditional knockout of PGAM5 in macrophages greatly alleviated OA symptoms and promoted anabolic metabolism of chondrocytes in vitro and in vivo.Mechanistically,we found that PGAM5 enhanced M1 polarization via AKT-mTOR/p38/ERK pathways,whereas inhibited M2 polarization via STAT6-PPARγpathway in murine bone marrow-derived macrophages.Furthermore,we found that PGAM5 directly dephosphorylated Dishevelled Segment Polarity Protein 2(DVL2)which resulted in the inhibition ofβ-catenin and repolarization of M2 macrophages into M1 macrophages.Conditional knockout of both PGAM5 andβ-catenin in macrophages significantly exacerbated osteoarthritis compared to PGAM5-deficient mice.Motivated by these findings,we successfully designed mannose modified fluoropolymers combined with siPGAM5 to inhibit PGAM5 specifically in synovial macrophages via intra-articular injection,which possessed desired targeting abilities of synovial macrophages and greatly attenuated murine osteoarthritis.Collectively,these findings defined a key role for PGAM5 in orchestrating macrophage polarization and provides insights into novel macrophage-targeted strategy for treating OA.
文摘BACKGROUND While Singapore attains good health outcomes,Singapore’s healthcare system is confronted with bed shortages and prolonged stays for elderly people recovering from surgery in acute hospitals.An Acute Hospital-Community Hospital(AHCH)care bundle has been developed to assist patients in postoperative rehabilitation.The core concept is to transfer patients out of AHs when clinically recommended and into CHs,where they can receive more beneficial dedicated care to aid in their recovery,while freeing up bed capacities in AHs.AIM To analyze the AH length of stay(LOS),costs,and savings associated with the AH-CH care bundle intervention initiated and implemented in elderly patients aged 75 years and above undergoing elective orthopedic surgery.METHODS A total of 8621:1 propensity score-matched patients aged 75 years and above who underwent elective orthopedic surgery in Singapore General Hospital(SGH)before(2017-2018)and after(2019-2021)the care bundle intervention period was analyzed.Outcome measures were AH LOS,CH LOS,hospitalization metrics,postoperative 30-d mortality,and modified Barthel Index(MBI)scores.The costs of AH inpatient hospital stay in the matched cohorts were compared using cost data in Singapore dollars.RESULTS Of the 862 matched elderly patients undergoing elective orthopedic surgery before and after the care bundle intervention,the age distribution,sex,American Society of Anesthesiologists classification,Charlson Comorbidity Index,and surgical approach were comparable between both groups.Patients transferred to CHs after the surgery had a shorter median AH LOS(7 d vs 9 d,P<0.001).The mean total AH inpatient cost per patient was 14.9%less for the elderly group transferred to CHs(S$24497.3 vs S$28772.8,P<0.001).The overall AH U-turn rates for elderly patients within the care bundle were low,with a 0%mortality rate following orthopedic surgery.When elderly patients were discharged from CHs,their MBI scores increased significantly(50.9 vs 71.9,P<0.001).CONCLUSION The AH-CH care bundle initiated and implemented in the Department of Orthopedic Surgery appears to be effective and cost-saving for SGH.Our results indicate that transitioning care between acute and community hospitals using this care bundle effectively reduces AH LOS in elderly patients receiving orthopedic surgery.Collaboration between acute and community care providers can assist in closing the care delivery gap and enhancing service quality.
文摘Rarely,penetrating injuries to the spinal cord result from wooden objects,creating unique challenges to mitigate neurological injury and high rates of infection and foreign body reactions.We report a man who sustained a penetrating cervical spinal cord injury from a sharpened stick.While initially tetraparetic,he rapidly recovered function.The risks of neurological deterioration during surgical removal made the patient reluctant to consent to surgery despite the impalement of the spinal cord.A repeat MRI on day 3 showed an extension of edema indicating progressive inflammation.On the 7~(th)day after injury,fever and paresthesias occurred with a large increase in serum inflammatory indicators,and the patient agreed to undergo surgical removal of the wooden object.We discuss the management nuances related to wood,the longitudinal evolution of MRI findings,infection risk,surgical risk mitigation and technique,an inflammatory marker profile,long-term recovery,and the surprisingly minimal neurological deficits associated with low-velocity midline spinal cord injuries.The patient had an excellent clinical outcome.The main lessons are that a wooden penetrating central nervous system injury has a high risk for infection,and that surgical removal from the spinal cord should be performed soon after injury and under direct visualization.
基金Supported by National Natural Science Foundation of China,No.81860406Guangxi Natural Science Foundation,No.2023GXNSFAA026339Medical Excellence Award Funded by the Creative Research Development Grant from the First Affiliated Hospital of Guangxi Medical University.
文摘BACKGROUND East Asia is the most dynamic region in the world and includes three major countries:Japan,South Korea and China.Due to rapid economic growth,orthopedics research in East Asia has achieved great advances during the past 10 years.However,the current status of orthopedic research in Japan,South Korea and China is still unclear.AIM To understand the current status of orthopedic research in Japan,South Korea,and China.METHODS Journals listed in the“Orthopedics”category of Science Citation Index Expanded subject categories were included.The PubMed and Web of Knowledge electronic databases were searched to identify scientific publications from the selected journals written by researchers from Japan,South Korea and China.A systematic analysis was conducted to analyze orthopedic research articles published in the three countries based on the number of articles,study design,impact factors(IFs)and citations.Furthermore,we also ranked the top 10 countries worldwide with the highest publications in the past 10 years.Additionally,we ranked the top 10 countries with the highest number of publications in the world in the past 10 years.Statistical analyses were performed using SPSS 20.0 software(SPSS Inc.,Chicago,IL,United States),and statistical results are given in Tables and Figures.The Kruskal-Wallis test and the Mann-Whitney test were used to detect differences between countries.The tendency regarding the number of articles was analyzed by curvilinear regression.A two-tailed P<0.05 was considered significant.RESULTS From 2012-2021,a total of 144518 articles were published in the 86 selected orthopedic journals.During this period,the number of worldwide published orthopedic articles has shown an annual increasing trend.A total of 27164 orthopedic research articles were published by Japan,South Korea and China during the past 10 years;44.32%were from China,32.98%were from Japan,and 22.70%were from South Korea.From 2012 to 2021,the annual number of articles markedly increased in each of the three countries.Over time,the worldwide share of articles increased substantially in South Korea(3.37%to 6.53%,P<0.001)and China(5.29%to 9.61%,P<0.001).However,the worldwide share of articles significantly decreased in Japan(5.22%to 3.80%,P<0.001).The annual total IFs of articles from China were well above those of articles from Japan and South Korea(36597.69 vs 27244.48 vs 20657.83,P<0.05).There was no significant difference among the articles in the top 10 high-IF orthopedics journals published from those three countries[South Korea(800)>China(787)>Japan(646),P>0.05].CONCLUSION Over the past 10 years,China’s scientific publications in orthopedic journals have shown an increasing trend.Considering the relative scale of the populations,Japan and South Korea have outpaced China with respect to quality.
文摘Purpose: Implant subsidence is a possible complication of spinal interbody fusion. We aim to evaluate porous titanium cages subsidence, fusion and functional outcomes in patients subjected to oblique lumbar interbody fusion (OLIF) with these novel devices. Methods: Our institutional review board approved a single-center experience which included 60 patients who underwent OLIF from June 2018 to June 2020 utilizing the porous titanium implants. Data was collected in accordance with the Declaration of Helsinki, and written informed consent was obtained. Imaging studies including radiographs 1, 3, 6 and 12 months and computed tomography (CT) scan at 6 months obtained during routine postoperative follow-up visits, were studied for signs of implant subsidence, fusion and clinical parameters to determine the effectiveness of surgery such as Oswestry disability index (ODI). Results: Radiographic subsidence occurred in 1 out of 89 porous titanium interbody cages (1.1%). No subsidence was observed in the posterior screws and rods fixation group (N = 57). However, one case of subsidence occurred in the lateral plate fixation group (N = 3). The subsidence occurred in an osteoporotic elderly patient operated for adjacent segment disease, and she was later revised with posterior instrumentation using cemented screws and rods. She had an uneventful recovery. Fusion rates were evaluated under CT scan at 6 months with a rate of 88%. In terms of clinical outcomes, ODI decreased significantly from 20.3 preop to 10.7 postop with a P-value Conclusions: In our study, the subsidence rate was lower than previously reported in the literature. Also, we had good fusion rates at 6 months likely due to the porous titanium cages use. We had no subsidence in the posterior instrumented group and one case in the lateral fixation group with improved clinical outcomes.
基金supported by the National Natural Science Foundation of China, Nos. 82271411 (to RG), 51803072 (to WLiu)grants from the Department of Finance of Jilin Province, Nos. 2022SCZ25 (to RG), 2022SCZ10 (to WLiu), 2021SCZ07 (to RG)+2 种基金Jilin Provincial Science and Technology Program, No. YDZJ202201ZYTS038 (to WLiu)The Youth Support Programmed Project of China-Japan Union Hospital of Jilin University, No. 2022qnpy11 (to WLuo)The Project of China-Japan Union Hospital of Jilin University, No. XHQMX20233 (to RG)
文摘Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely studied.However,their inability to cross the blood–brain barrier hampers the clinical translation of these therapeutic strategies.Liposomes are nanoparticles composed of lipid bilayers,which can effectively encapsulate drugs and improve drug delivery across the blood–brain barrier and into brain tissue through their targeting and permeability.Therefore,they can potentially treat traumatic and nontraumatic central nervous system diseases.In this review,we outlined the common properties and preparation methods of liposomes,including thin-film hydration,reverse-phase evaporation,solvent injection techniques,detergent removal methods,and microfluidics techniques.Afterwards,we comprehensively discussed the current applications of liposomes in central nervous system diseases,such as Alzheimer's disease,Parkinson's disease,Huntington's disease,amyotrophic lateral sclerosis,traumatic brain injury,spinal cord injury,and brain tumors.Most studies related to liposomes are still in the laboratory stage and have not yet entered clinical trials.Additionally,their application as drug delivery systems in clinical practice faces challenges such as drug stability,targeting efficiency,and safety.Therefore,we proposed development strategies related to liposomes to further promote their development in neurological disease research.
基金supported by the Key Research Projects of Universities of Henan Province,No.21A320064 (to XS)the National Key Research and Development Program of China,No.2021YFA1201504 (to LZ)+1 种基金the Strategic Priority Research Program of the Chinese Academy of Science,No.XDB36000000 (to CW)the National Natural Science Foundation of China,Nos.31971295,12374406 (both to LZ)。
文摘Spinal cord injuries lead to significant loss of motor, sensory, and autonomic functions, presenting major challenges in neural regeneration. Achieving effective therapeutic concentrations at injury sites has been a slow process, partly due to the difficulty of delivering drugs effectively. Nanoparticles, with their targeted delivery capabilities, biocompatibility, and enhanced bioavailability over conventional drugs, are garnering attention for spinal cord injury treatment. This review explores the current mechanisms and shortcomings of existing treatments, highlighting the benefits and progress of nanoparticle-based approaches. We detail nanoparticle delivery methods for spinal cord injury, including local and intravenous injections, oral delivery, and biomaterial-assisted implantation, alongside strategies such as drug loading and surface modification. The discussion extends to how nanoparticles aid in reducing oxidative stress, dampening inflammation, fostering neural regeneration, and promoting angiogenesis. We summarize the use of various types of nanoparticles for treating spinal cord injuries, including metallic, polymeric, protein-based, inorganic non-metallic, and lipid nanoparticles. We also discuss the challenges faced, such as biosafety, effectiveness in humans, precise dosage control, standardization of production and characterization, immune responses, and targeted delivery in vivo. Additionally, we explore future directions, such as improving biosafety, standardizing manufacturing and characterization processes, and advancing human trials. Nanoparticles have shown considerable progress in targeted delivery and enhancing treatment efficacy for spinal cord injuries, presenting significant potential for clinical use and drug development.
文摘BACKGROUND:Adeno-associated virus(AAV)gene therapy has been proven to be reliable and safe for the treatment of osteoarthritis in recent years.However,given the complexity of osteoarthritis pathogenesis,single gene manipulation for the treatment of osteoarthritis may not produce satisfactory results.Previous studies have shown that nuclear factorκB could promote the inflammatory pathway in osteoarthritic chondrocytes,and bone morphogenetic protein 4(BMP4)could promote cartilage regeneration.OBJECTIVE:To test whether combined application of AAV-p65shRNA and AAV-BMP4 will yield the synergistic effect on chondrocytes regeneration and osteoarthritis treatment.METHODS:Viral particles containing AAV-p65-shRNA and AAV-BMP4 were prepared.Their efficacy in inhibiting inflammation in chondrocytes and promoting chondrogenesis was assessed in vitro and in vivo by transfecting AAV-p65-shRNA or AAV-BMP4 into cells.The experiments were divided into five groups:PBS group;osteoarthritis group;AAV-BMP4 group;AAV-p65shRNA group;and BMP4-p65shRNA 1:1 group.Samples were collected at 4,12,and 24 weeks postoperatively.Tissue staining,including safranin O and Alcian blue,was applied after collecting articular tissue.Then,the optimal ratio between the two types of transfected viral particles was further investigated to improve the chondrogenic potential of mixed cells in vivo.RESULTS AND CONCLUSION:The combined application of AAV-p65shRNA and AAV-BMP4 together showed a synergistic effect on cartilage regeneration and osteoarthritis treatment.Mixed cells transfected with AAV-p65shRNA and AAV-BMP4 at a 1:1 ratio produced the most extracellular matrix synthesis(P<0.05).In vivo results also revealed that the combination of the two viruses had the highest regenerative potential for osteoarthritic cartilage(P<0.05).In the present study,we also discovered that the combined therapy had the maximum effect when the two viruses were administered in equal proportions.Decreasing either p65shRNA or BMP4 transfected cells resulted in less collagen II synthesis.This implies that inhibiting inflammation by p65shRNA and promoting regeneration by BMP4 are equally important for osteoarthritis treatment.These findings provide a new strategy for the treatment of early osteoarthritis by simultaneously inhibiting cartilage inflammation and promoting cartilage repair.
文摘In clinical practice,cervical spine surgery inevitably alters the original physiological structure of the cervical spine,thus causing changes in the original biomechanical properties of the cervical spine.The biomechanical properties of the cervical spine are particularly significant as it is an essential structure that supports the head and connects the trunk.Different cervical spine surgery options can have different effects on the biomechanics of the cervical spine.Therefore,this review will discuss recent research advances on the effects of cervical spine surgery on cervical spine biomechanics.We hope that this review will provide some theoretical basis for future studies on the biomechanical effects of cervical spine surgery on the cervical spine.
基金This research was supported by NIH National Institute on Aging under Award Number R01 AG076783,R01 AG068997 and P01 AG066603(to X.C.).
文摘Bone is a mechanosensitive tissue and undergoes constant remodeling to adapt to the mechanical loading environment.However,it is unclear whether the signals of bone cells in response to mechanical stress are processed and interpreted in the brain.In this study,we found that the hypothalamus of the brain regulates bone remodeling and structure by perceiving bone prostaglandin E2(PGE2)concentration in response to mechanical loading.Bone PGE2 levels are in proportion to their weight bearing.When weight bearing changes in the tail-suspension mice,the PGE2 concentrations in bones change in line with their weight bearing changes.Deletion of cyclooxygenase-2(COX2)in the osteoblast lineage cells or knockout of receptor 4(EP4)in sensory nerve blunts bone formation in response to mechanical loading.Moreover,knockout of TrkA in sensory nerve also significantly reduces mechanical load-induced bone formation.Moreover,mechanical loading induces cAMP-response element binding protein(CREB)phosphorylation in the hypothalamic arcuate nucleus(ARC)to inhibit sympathetic tyrosine hydroxylase(TH)expression in the paraventricular nucleus(PVN)for osteogenesis.Finally,we show that elevated PGE2 is associated with ankle osteoarthritis(AOA)and pain.Together,our data demonstrate that in response to mechanical loading,skeletal interoception occurs in the form of hypothalamic processing of PGE2-driven peripheral signaling to maintain physiologic bone homeostasis,while chronically elevated PGE2 can be sensed as pain during AOA and implication of potential treatment.
文摘BACKGROUND Simple bone cysts(SBC)are benign tumor-like bone lesions typically identified in children.While SBC may lead to growth disturbances or growth arrest,such cases are uncommon.The mechanisms behind these observations remain unclear.Additionally,research on the etiology of SBC remains inconclusive,and there has been no consensus on the appropriate timing and methodology for treatment.CASE SUMMARY Here,we present our experience in the successful surgical management of a 10-year-old girl with SBC,who presented with a pathological fracture complicated by malunion of the displaced fracture,varus deformity,and limb length discrepancy.We hypothesized two possible etiologies for the patient’s growth arrest and subsequent humerus varus deformity:(1)Direct disruption of the physis by fluid from the cyst itself;and(2)damage to the epiphysis due to repetitive pathological fractures associated with SBC.In addressing this case,surgical intervention was undertaken to correct the proximal humerus varus deformity.This approach offered the advantages of simultaneously correcting angular abnormalities,achieving mild limb lengthening,providing definitive SBC treatment,and reducing the overall treatment duration.CONCLUSION As per current literature,acute correction of acute angular deformity in proximal humeral SBC is not well comprehended.However,in this specific case,acute correction was considered an optimal solution.
基金CAMS Innovation Fund for Medical Sciences,No.2022-I2M-C&T-B-034.
文摘Peripheral nerve injury(PNI)is a common neurological disorder and complete functional recovery is difficult to achieve.In recent years,bone marrow mesenchymal stem cells(BMSCs)have emerged as ideal seed cells for PNI treatment due to their strong differentiation potential and autologous trans-plantation ability.This review aims to summarize the molecular mechanisms by which BMSCs mediate nerve repair in PNI.The key mechanisms discussed include the differentiation of BMSCs into multiple types of nerve cells to promote repair of nerve injury.BMSCs also create a microenvironment suitable for neuronal survival and regeneration through the secretion of neurotrophic factors,extracellular matrix molecules,and adhesion molecules.Additionally,BMSCs release pro-angiogenic factors to promote the formation of new blood vessels.They modulate cytokine expression and regulate macrophage polarization,leading to immunomodulation.Furthermore,BMSCs synthesize and release proteins related to myelin sheath formation and axonal regeneration,thereby promoting neuronal repair and regeneration.Moreover,this review explores methods of applying BMSCs in PNI treatment,including direct cell trans-plantation into the injured neural tissue,implantation of BMSCs into nerve conduits providing support,and the application of genetically modified BMSCs,among others.These findings confirm the potential of BMSCs in treating PNI.However,with the development of this field,it is crucial to address issues related to BMSC therapy,including establishing standards for extracting,identifying,and cultivating BMSCs,as well as selecting application methods for BMSCs in PNI such as direct transplantation,tissue engineering,and genetic engineering.Addressing these issues will help translate current preclinical research results into clinical practice,providing new and effective treatment strategies for patients with PNI.
基金the institutional review board of Mingzhou Hospital of Ningbo(No.202208501).
文摘BACKGROUND The pedicle screw technique is widely employed for vertebral body fixation in the treatment of spinal disorders.However,traditional screw placement methods require the dissection of paraspinal muscles and the insertion of pedicle screws at specific transverse section angles(TSA).Larger TSA angles require more force to pull the muscle tissue,which can increase the risk of surgical trauma and ischemic injury to the lumbar muscles.AIM To study the feasibility of zero-degree TSA vertical pedicle screw technique in the lumbosacral segment.METHODS Finite element models of vertebral bodies and pedicle screw-rod systems were established for the L4-S1 spinal segments.A standard axial load of 500 N and a rotational torque of 10 N/m were applied.Simulated screw pull-out experiment was conducted to observe pedicle screw resistance to pull-out,maximum stress,load-displacement ratio,maximum stress in vertebral bodies,load-displacement ratio in vertebral bodies,and the stress distribution in pedicle screws and vertebral bodies.Differences between the 0-degree and 17-degree TSA were compared.RESULTS At 0-degree TSA,the screw pull-out force decreased by 11.35%compared to that at 17-degree TSA(P<0.05).At 0-degree and 17-degree TSA,the stress range in the screw-rod system was 335.1-657.5 MPa and 242.8-648.5 MPa,separately,which were below the fracture threshold for the screw-rod system(924 MPa).At 0-degree and 17-degree TSA,the stress range in the vertebral bodies was 68.45-78.91 MPa and 39.08-72.73 MPa,separately,which were below the typical bone yield stress range for vertebral bodies(110-125 MPa).At 0-degree TSA,the load-displacement ratio for the vertebral bodies and pedicle screws was slightly lower compared to that at 17-degree TSA,indicating slightly lower stability(P<0.05).CONCLUSION The safety and stability of 0-degree TSA are slightly lower,but the risks of screw-rod system fracture,vertebral body fracture,and rupture are within acceptable limits.
文摘BACKGROUND Advances in implant material and design have allowed for improvements in total knee arthroplasty(TKA)outcomes.A cruciate retaining(CR)TKA provides the least constraint of TKA designs by preserving the native posterior cruciate ligament.Limited research exists that has examined clinical outcomes or patient reported outcome measures(PROMs)of a large cohort of patients undergoing a CR TKA utilizing a kinematically designed implant.It was hypothesized that the studied CR Knee System would demonstrate favorable outcomes and a clinically significant improvement in pain and functional scores.AIM To assess both short-term and mid-term clinical outcomes and PROMs of a novel CR TKA design.METHODS A retrospective,multi-surgeon study identified 255 knees undergoing a TKA utilizing a kinematically designed CR Knee System(JOURNEY™II CR;Smith and Nephew,Inc.,Memphis,TN)at an urban,academic medical institution between March 2015 and July 2021 with a minimum of two-years of clinical follow-up with an orthopedic surgeon.Patient demographics,surgical information,clinical outcomes,and PROMs data were collected via query of electronic medical records.The PROMs collected in the present study included the Knee Injury and Osteoarthritis Outcome Score for Joint Replacement(KOOS JR)and Patient-Reported Outcomes Measurement Information System(PROMIS■)scores.The significance of improvements in mean PROM scores from preoperative scores to scores collected at six months and two-years postoperatively was analyzed using Independent Samples t-tests.RESULTS Of the 255 patients,65.5%were female,43.8%were White,and patients had an average age of 60.6 years.Primary osteoarthritis(96.9%)was the most common primary diagnosis.The mean surgical time was 105.3 minutes and mean length of stay was 2.1 d with most patients discharged home(92.5%).There were 18 emergency department(ED)visits within 90 d of surgery resulting in a 90 d ED visit rate of 7.1%,including a 2.4%orthopedic-related ED visit rate and a 4.7%non-orthopedic-related ED visit rate.There were three(1.2%)hospital readmissions within 90 d postoperatively.With a mean time to latest follow-up of 3.3 years,four patients(1.6%)required revision,two for arthrofibrosis,one for aseptic femoral loosening,and one for peri-prosthetic joint infection.There were significant improvements in KOOS JR,PROMIS Pain Intensity,PROMIS Pain Interference,PROMIS Mobility,and PROMIS Physical Health from preoperative scores to six month and two-year postoperative scores.CONCLUSION The evaluated implant is an effective,novel design offering excellent outcomes and low complication rates.At a mean follow up of 3.3 years,four patients required revisions,three aseptic and one septic,resulting in an overall implant survival rate of 98.4%and an aseptic survival rate of 98.8%.The results of our study demonstrate the utility of this kinematically designed implant in the setting of primary TKA.
文摘BACKGROUND Congenital absence of the menisci is a rare anatomical variation characterized by the absence or underdevelopment of one or both menisci in the knee joint.The menisci are crucial in load distribution,joint stability,and shock absorption.Understanding the clinical presentation,diagnosis,and management of this condition is important for optimal patient care.CASE SUMMARY A 27-year-old male with a long-standing history of knee pain underwent diagnostic arthroscopy,revealing a congenital absence of the meniscus.The patient's clinical findings,imaging results,surgical procedures,and pertinent images are detailed.This case presents a unique aspect with the congenital absence of the meniscus,contributing valuable insights to the literature on rare anatomical anomalies.CONCLUSION This case of congenital absence of the menisci highlights the diagnostic challenges posed by rare anomalies.The diagnostic arthroscopy played a crucial role in identifying the absence of the meniscus and providing an explanation for the patient's persistent knee pain.The case underscores the importance of individualized treatment approaches,including physical therapy,for optimal management of rare meniscal anomalies.Further research is warranted to explore effective management strategies for the aforementioned cases and to expand our knowledge of these rare conditions.
基金supported by the National Natural Science Foundation of China(82072432)the China-Japan Friendship Hospital Horizontal Project/Spontaneous Research Funding(2022-HX-JC-7)+1 种基金the National High Level Hospital Clinical Research Funding(2022-NHLHCRF-PY-20)the Elite Medical Professionals project of China-Japan Friendship Hospital(ZRJY2021-GG12).
文摘Rheumatoid arthritis(RA)is a systemic autoimmune disease that is primarily manifested as synovitis and polyarticular opacity and typically leads to serious joint damage and irreversible disability,thus adversely affecting locomotion ability and life quality.Consequently,good prognosis heavily relies on the early diagnosis and effective therapeutic monitoring of RA.Activatable fluorescent probes play vital roles in the detection and imaging of biomarkers for disease diagnosis and in vivo imaging.Herein,we review the fluorescent probes developed for the detection and imaging of RA biomarkers,namely reactive oxygen/nitrogen species(hypochlorous acid,peroxynitrite,hydroxyl radical,nitroxyl),pH,and cysteine,and address the related challenges and prospects to inspire the design of novel fluorescent probes and the improvement of their performance in RA studies.
文摘BACKGROUND Diabetic foot(DMF)complications are common and are increasing in incidence.Risk factors related to wound complications are yet to be established after transtibial amputation under the diagnosis of DMF infection.AIM To analyze the prognosis and risk factors related to wound complications after transtibial amputation in patients with diabetes.METHODS This retrospective cohort study included seventy-two patients with DMF complications who underwent transtibial amputation between April 2014 and March 2023.The groups were categorized based on the occurrence of wound complications,and we compared demographic data between the complication group and the non-complication group to analyze risk factors.Moreover,a multivariate logistic regression analysis was performed to identify risk factors.RESULTS The average follow-up period was 36.2 months.Among the 72 cases,31(43.1%)had wound complications.Of these,12 cases(16.7%)received further treatment,such as debridement,soft tissue stump revision,and re-amputation at the proximal level.In a group that required further management due to wound complications after transtibial amputation,the hemoglobin A1c(HbA1c)level was 9.32,while the other group that did not require any treatment had a 7.54 HbA1c level.The prevalence of a history of kidney transplantation with wound complications after transtibial amputation surgery in DMF patients was significantly greater than in cases without wound complications(P=0.02).Other factors did not show significant differences.CONCLUSION Approximately 43.1%of the patients with transtibial amputation surgery experienced wound complications,and 16.7%required additional surgical treatment.High HbA1c levels and kidney transplant history are risk factors for postoperative wound complications.
基金supported by Project of the Health Shanghai Initiative Special Fund(Medical-Sports Integration,Creating a New Model of Exercise for Health),No.JKSHZX-2022-02(to SC).
文摘Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural regeneration.The role of the small ubiquitin-like modifier(SUMO)protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of SUMOylation.We used machine learning to create the exercise and SUMO-related gene signature(ESLRS).This signature shows how physical activity might help improve the outlook for low-grade glioma and other cancers.We demonstrated the prognostic and immunotherapeutic significance of ESLRS markers,specifically highlighting how murine double minute 2(MDM2),a component of the ESLRS,can be targeted by nutlin-3.This underscores the intricate relationship between natural compounds such as nutlin-3 and immune regulation.Using comprehensive CRISPR screening,we validated the effects of specific ESLRS genes on low-grade glioma progression.We also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic simulation.Nutlin-3a inhibited glioma cell proliferation and activated the p53 pathway.Its efficacy decreased with MDM2 overexpression,and this was reversed by Nutlin-3a or exercise.Experiments using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway regulation.Notably,both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing cells.These results suggest the potential for Nutlin-3a,an MDM2 inhibitor,with physical exercise as a therapeutic approach for glioma management.Our research also supports the use of natural products for therapy and sheds light on the interaction of exercise,natural products,and immune regulation in cancer treatment.