BMSC-derived Exosomes Ameliorate Peritoneal Dialysis-associated Peritoneal Fibrosis via the Mir-27a-3p/TP53 Pathway

Objective:Peritoneal fibrosis(PF)is the main cause of declining efficiency and ultrafiltration failure of the peritoneum,which restricts the long-term application of peritoneal dialysis(PD).This study aimed to investigate the therapeutic effects and mechanisms of bone marrow mesenchymal stem cells-derived exosomes(BMSC-Exos)on PF in response to PD.Methods:Small RNA sequencing analysis of BMSC-Exos was performed by second-generation sequencing.C57BL/6J mice were infused with 4.25%glucose-based peritoneal dialysis fluid(PDF)for 6 consecutive weeks to establish a PF model.A total of 36 mice were randomly divided into 6 groups:control group,1.5%PDF group,2.5%PDF group,4.25%PDF group,BMSC-Exos treatment group,and BMSC-Exos+TP53 treatment group.Reverse transcription quantitative polymerase chain reaction(RT-qPCR)was performed to measure the expression level of miR-27a-3p in BMSC-Exos and peritoneum of mice treated with different concentrations of PDF.HE and Masson staining were performed to evaluate the extent of PF.The therapeutic potential of BMSC-Exos for PF was examined through pathological examination,RT-qPCR,Western blotting,and peritoneal function analyses.Epithelial-mesenchymal transition(EMT)of HMrSV5 was induced with 4.25%PDF.Cells were divided into control group,4.25%PDF group,BMSC-Exos treatment group,and BMSC-Exos+TP53 treatment group.Cell Counting Kit-8 assay was used to measure cell viability,and transwell migration assay was used to verify the capacity of BMSC-Exos to inhibit EMT in HMrSV5 cells.Results:Small RNA sequencing analysis showed that miR-27a-3p was highly expressed in BMSC-derived exosomes compared to BMSCs.The RT-qPCR results showed that the expression of miR-27a-3p was upregulated in BMSC-Exos,but decreased in PD mice.We found that PF was glucose concentration-dependently enhanced in the peritoneum of the PD mice.Compared with the control mice,the PD mice showed high solute transport and decreased ultrafiltration volume as well as an obvious fibroproliferative response,with markedly increased peritoneal thickness and higher expression ofα-SMA,collagen-I,fibronectin,and ECM1.The mice with PD showed decreased miR-27a-3p.Peritoneal structural and functional damage was significantly attenuated after BMSC-Exos treatment,while PF and mesothelial damage were significantly ameliorated.Additionally,markers of fibrosis(α-SMA,collagen-I,fibronectin,ECM1)and profibrotic cytokines(TGF-β1,PDGF)were downregulated at the mRNA and protein levels after BMSC-Exos treatment.In HMrSV5 cells,BMSC-Exos reversed the decrease in cell viability and the increase in cell migratory capacity caused by high-glucose PDF.Western blotting and RT-qPCR analysis revealed that BMSC-Exos treatment resulted in increased expression of E-cadherin(epithelial marker)and decreased expression ofα-SMA,Snail,and vimentin(mesenchymal markers)compared to those of the 4.25%PDF-treated cells.Importantly,a dual-luciferase reporter assay showed that TP53 was a target gene of miR-27a-3p.TP53 overexpression significantly reversed the decreases in PF and EMT progression induced by BMSC-Exos.Conclusion:The present results demonstrate that BMSC-Exos showed an obvious protective effect on PD-related PF and suggest that BMSC-derived exosomal miR-27a-3p may exert its inhibitory effect on PF and EMT progression by targeting TP53.

A new perspective on intervertebral disc calcification—from bench to bedside

Disc degeneration primarily contributes to chronic low back and neck pain.Consequently,there is an urgent need to understand the spectrum of disc degeneration phenotypes such as fibrosis,ectopic calcification,herniation,or mixed phenotypes.Amongst these phenotypes,disc calcification is the least studied.Ectopic calcification,by definition,is the pathological mineralization of soft tissues,widely studied in the context of conditions that afflict vasculature,skin,and cartilage.Clinically,disc calcification is associated with poor surgical outcomes and back pain refractory to conservative treatment.It is frequently seen as a consequence of disc aging and progressive degeneration but exhibits unique molecular and morphological characteristics:hypertrophic chondrocyte-like cell differentiation;TNAP,ENPP1,and ANK upregulation;cell death;altered Pi and PPi homeostasis;and local inflammation.Recent studies in mouse models have provided a better understanding of the mechanisms underlying this phenotype.It is essential to recognize that the presentation and nature of mineralization differ between AF,NP,and EP compartments.Moreover,the combination of anatomic location,genetics,and environmental stressors,such as aging or trauma,govern the predisposition to calcification.Lastly,the systemic regulation of calcium and Pi metabolism is less important than the local activity of PPi modulated by the ANK-ENPP1 axis,along with disc cell death and differentiation status.While there is limited understanding of this phenotype,understanding the molecular pathways governing local intervertebral disc calcification may lead to developing disease-modifying drugs and better clinical management of degeneration-related pathologies.

Prospective Cohort Investigation on Physical Activity of Osteoporosis Outcomes(PAOPO)in Jidong:Objectives,Study Design,and Baseline Characteristics

Objective The aim of this study was to investigate the prospective association between physical activity(PA),independently or in conjunction with other contributing factors,and osteoporosis(OP)outcomes.Methods The Physical Activity in Osteoporosis Outcomes(PAOPO)study was a community-based cohort investigation.A structured questionnaire was used to gather the participants’sociodemographic characteristics.Bone mineral density(BMD)measurements were performed to assess OP outcomes,and the relationship between BMD and OP was evaluated within this cohort.Results From 2013 to 2014,8,471 participants aged 18 years and older were recruited from Tangshan,China’s Jidong community.Based on their PA level,participants were categorized as inactive,moderately active,or very active.Men showed higher physical exercise levels than women across the activity groups.BMD was significantly higher in the very active group than in the moderately active and inactive groups.Individuals aged>50 years are at a higher risk of developing OP and osteopenia.Conclusion The PAOPO study offers promising insights into the relationship between PA and OP outcomes,encouraging the implementation of PA in preventing and managing OP.

Safety of tranexamic acid in surgically treated isolated spine trauma

BACKGROUND Tranexamic acid(TXA),a synthetic antifibrinolytic drug,effectively reduces blood loss by inhibiting plasmin-induced fibrin breakdown.This is the first study in the United Kingdom to investigate the effectiveness of TXA in the surgical management of isolated spine trauma.AIM To assess the safety of TXA in isolated spine trauma.The primary and secondary outcomes are to assess the rate of thromboembolic events and to evaluate blood loss and the incidence of blood transfusion,respectively.METHODS This prospective observational study included patients aged≥17 years with isolated spine trauma requiring surgical intervention over a 6-month period at two major trauma centers in the United Kingdom.RESULTS We identified 67 patients:26(39%)and 41(61%)received and did not receive TXA,respectively.Both groups were matched in terms of age,gender,American Society of Anesthesiologists grade,and mechanism of injury.A higher proportion of patients who received TXA had a subaxial cervical spine injury classification or thoracolumbar injury classification score>4(74%vs 56%).All patients in the TXA group underwent an open approach with a mean of 5 spinal levels involved and an average operative time of 203 min,compared with 24 patients(58%)in the non TXA group who underwent an open approach with an average of 3 spinal levels involved and a mean operative time of 159 min.Among patients who received TXA,blood loss was<150 and 150–300 mL in 8(31%)and 15(58%)patients,respectively.There were no cases of thromboembolic events in any patient who received TXA.CONCLUSION Our study demonstrated that TXA is safe for isolated spine trauma.It is challenging to determine whether TXA effectively reduces blood loss because most surgeons prefer TXA for open or multilevel cases.Further,larger studies are necessary to explore the rate,dosage,and mode of administration of TXA.

Mechanisms of shoulder trauma: Current concepts

Acute traumatic injuries to the glenohumeral articulation are common.The types of injuries depend on age,muscle strength,bone density,and biomechanics of the traumatic event.Understanding the different mechanisms of trauma and how they affect the functional anatomical structures of the shoulder joint is crucial for the treatment of these lesions.Therefore,when clinicians have knowledge of these mechanisms they can accurately diagnose and treat shoulder pathology and predict distinct injury patterns.Here,we have described the fundamentals of the mechanisms of injury of the glenohumeral dislocation,dislocation with fracture of the humeral head,and the proximal humerus fracture.We have focused on common injury mechanisms and the correlation with radiological diagnostics.Radiological and laboratory findings of distinct types of injury were also discussed.

Early Treatment Outcome of Humeral Shaft Fracture Non-Union in Adults: Comparative Study of Plating versus Interlocking Nailing

Background: Fractures of humeral shaft in adults are common injuries. Humeral shafts non-union either from late presentation after initial treatment by traditional bone setters or failed non-operative orthodox care is a major problem in this part of the world. This non-union is a major treatment challenge with increased cost of care and morbidity in this part of the world. Humeral shaft non-union can be treated with locked intra-medullary nailing (LIMN) or dynamic compression plating (DCP). Study on comparison of these methods of fixation in this part of the world is scarce in literature search, hence the reason for this study. Objective: The objectives of this study are: (1) to compare early clinical outcome following fixation of humeral shaft fracture nonunion with DCP versus LIMN;(2) to compare the time of radiologic fracture union of DCP with LIMN;(3) to compare complications following fixation of humeral shaft fracture nonunion with DCP versus LIMN. Patients and Methods: This was a randomized control study done for 2 years in which fifty adult patients with humeral shaft non-union were recruited. The patients were grouped into 2 (P = DCP & N = LIMN). Forty five of the patients completed the follow up periods of the study and then analyzed. The P group had ORIF with DCP while the N group had ORIF with LIMN. Both groups had grafting with cancellous bones. Each patient was followed up for a period of 6 months at the time which radiographic union is expected. Any patient without clinical and/or radiographic evidence of union after six months of surgery was diagnosed as having recurrent non-union. The data generated was analyzed using SPSS Version 23. The results were presented in charts and tables. The paired t-test was used while considering p value Result: Forty five patients completed follow up. There was a male preponderance (4:1), right humerus predominated (3:2). Motor vehicular accidents were the commonest cause of the fractures (62%). Most non-union fractures occurred at the level of the middle 3rd of the humeral shaft (60%). Failed TBS treatment was the commonest indication for the osteosynthesis (71%). More patients had plating (53%) compared to 47% who had LIMN. Most patients (93.4%) had union between 3 to 6 months irrespective of fixation type with no significant statistical difference between the union rate of DCP and LIMN (p value 0.06) with similar functional outcome and complication rates irrespective of the type of fixation. Conclusion: This study showed that the success rates in term of fracture union, outcome functional grades and complication rates were not directly dependent on the types of the fixation: plating or locked intra-medullary nailing.

Carpal Tunnel Syndrome: A Marker for Amyloidosis

Introduction: Amyloidosis are systemic conditions and carpal tunnel syndrome (CTS) precedes the principal systemic complications and can be used as an early marker. Our objective was to determine the frequency of amyloid deposition in idiopathic CTS and its systemic impact. Methods: We retrospectively evaluated patients with CTS between September 2019 to January 2020. Samples from the anterior carpal ligament were pathologically evaluated and amyloid deposition was confirmed by apple-green birefringence on polarized light using Congo red stain. When amyloid was detected we performed genetic testing for transthyretin variants (ATTRv), immunofixation electrophoresis in serum and urine for light chains and multidisciplinary evaluation. Results: Thirty consecutive patients were included, 19 women, 11 men, mean age 70 years old (range 42 - 89 years). We identified 3 patients (10%) with amyloid deposits (mean age: 78.6 years, 2 men, 1 woman). Genetic testing for ATTRv and light chains studies were negative. During follow-up: The first patient required aortic valve replacement. The second patient developed progressive cardiac failure with syncopal episodes, atrioventricular block and atrial fibrillation and required a pacemaker and anticoagulation. The third patient had unexplained chronic edemas. The cardiac evaluation in all 3 patients revealed left ventricular hypertrophy and myocardial uptake (Perugini Score > 2) in their nuclear bone scintigraphies with technetium pyrophosphate. Two patients were treated with tafamidis and one patient died due to refractory cardiac insufficiency. Discussion: Our findings underline the importance of investigating amyloidosis in idiopathic CTS. The identification of deposits allows early diagnosis of cardiac amyloidosis leading to timely intervention and treatment.

Three predictive scores compared in a retrospective multicenter study of nonunion tibial shaft fracture

BACKGROUND Delayed union,malunion,and nonunion are serious complications in the healing of fractures.Predicting the risk of nonunion before or after surgery is challenging.AIM To compare the most prevalent predictive scores of nonunion used in clinical practice to determine the most accurate score for predicting nonunion.METHODS We collected data from patients with tibial shaft fractures undergoing surgery from January 2016 to December 2020 in three different trauma hospitals.In this retrospective multicenter study,we considered only fractures treated with intramedullary nailing.We calculated the tibia FRACTure prediction healING days(FRACTING)score,Nonunion Risk Determination score,and Leeds-Genoa Nonunion Index(LEG-NUI)score at the time of definitive fixation.RESULTS Of the 130 patients enrolled,89(68.4%)healed within 9 months and were classified as union.The remaining patients(n=41,31.5%)healed after more than 9 months or underwent other surgical procedures and were classified as nonunion.After calculation of the three scores,LEG-NUI and FRACTING were the most accurate at predicting healing.CONCLUSION LEG-NUI and FRACTING showed the best performances by accurately predicting union and nonunion.

Robotics in total knee replacement:Current use and future implications

Robotic total knee replacement(TKR)surgery has evolved over the years with the aim of improving the overall 80% satisfaction rate associated with TKR surgery.Proponents claim higher precision in executing the pre-operative plan which results in improved alignment and possibly better clinical outcomes.Opponents suggest longer operative times with potentially higher complications and no superiority in clinical outcomes alongside increased costs.This editorial will summarize where we currently stand and the future implications of using robotics in knee replacement surgery.

Evaluation of Functional and Radiological Outcome of Arthroscopic-Assisted Anatomical Coracoclavicular (CC) and Acromioclavicular (AC) Ligament Reconstruction in Chronic AC Joint Dislocation

Introduction: Acromioclavicular (AC) joint dislocation is a common shoulder injury, comprising 9% - 12% of shoulder girdle injuries. Optimal management remains challenging, with treatment decisions guided by the Rockwood classification system. Controversies surround grade III injuries, necessitating further classification. Non-operative treatment has shown favorable outcomes, while surgical interventions vary. Anatomical coracoclavicular reconstruction (ACCR) has demonstrated biomechanical advantages over traditional methods. Arthroscopic techniques offer advantages, minimizing deltoid detachment and allowing concurrent pathology identification. This study evaluates the outcomes of arthroscopic-assisted ACCR in chronic AC joint dislocation. Surgical Technique: Arthroscopic-assisted ACCR involves meticulous portal placement, tendon graft harvesting, diagnostic arthroscopy, and coracoid exposure. The clavicle tunnels were made to mimic the conoid and trapezoid ligament positions, using FibreTape#2 loop and Dog Bone Button for correct placement against the coracoid base, and passing the semitendinosus graft through to reconstruct the conoid ligament, reduction done and graft follow through for anatomical reconstruction. Methods: A retrospective cohort study at Hospital Kuala Lumpur analyzed 35 patients undergoing arthroscopic-assisted ACCR for Rockwood grade III - V AC joint dislocations. Inclusion criteria encompassed trauma ≥ 3 weeks prior, no prior shoulder injuries, and ≥12-month follow-up. Functional and radiological assessments utilized ASES scores and coracoclavicular distances, respectively. Statistical analysis employed descriptive statistics and logistic regression. Results: The mean age was 38.9 years (SD 11.26), and 34 of 35 patients were male. Grade IV injuries were predominant (37.1%). Waiting time for surgery averaged 234.9 days. Functional improvement was substantial postoperatively (ASES: 55.5 to 88.9). Radiological outcomes demonstrated reduced coracoclavicular distances and maintained reduction. No significant correlation was observed between injury grade and outcomes. Conclusion: Arthroscopic-assisted ACCR for chronic AC joint dislocation yields significant functional and radiological improvement, irrespective of injury grade. Waiting time for surgery exhibits minor impact on outcomes, emphasizing the procedure’s efficacy. Concomitant injuries do not impede success, highlighting the versatility of this approach in managing shoulder instability. The study contributes valuable insights into the nuanced management of chronic AC joint dislocations and supports the adoption of arthroscopic-assisted ACCR as a viable treatment option.

Lab results of COVID-19 patients:Omicron vs delta variants

BACKGROUND The coronavirus disease 2019(COVID-19)virus has been a world-known pan-demic since February 2020.Multiple variances had been established;the most common variants in Israel were omicron and delta.AIM To analyze and compare laboratory values in the"omicron"and"delta"variants of the coronavirus by conducting follow-up examinations and laboratory audits on COVID-19 patients admitted to our institution.METHODS A retrospective study,two groups,50 patients in each group.Patients examined positive for COVID-19 were divided into groups according to the common variant at the given time.We reviewed demographic data and laboratory results such as complete blood count and full chemistry,including electrolytes and coagulation parameters.RESULTS The mean age was 52%,66.53±21.7 were female.No significance was found comparing laboratory results in the following disciplines:Blood count,hemo-globin,and lymphocytes(P=0.41,P=0.87,P=0.97).Omicron and delta variants have higher neutrophil counts,though they are not significantly different(P=0.38).Coagulation tests:Activated paritial thromoplastin test and international normalized ratio(P=0.72,P=0.68).We found no significance of abnormality for all electrolytes.CONCLUSION The study compares laboratory results of blood tests between two variants of the COVID-19 virus–omicron and delta.We found no significance between the variants.Our results show the need for further research with larger data as well as the need to compare all COVID-19 variants.

Diamond-Like Carbon Depositing on the Surface of Polylactide Membrane for Prevention of Adhesion Formation During Tendon Repair

Post-traumatic peritendinous adhesion presents a significant challenge in clinical medicine.This study proposes the use of diamond-like carbon(DLC)deposited on polylactic acid(PLA)membranes as a biophysical mechanism for anti-adhesion barrier to encase ruptured tendons in tendon-injured rats.The results indicate that PLA/DLC composite membrane exhibits more efficient anti-adhesion effect than PLA membrane,with histological score decreasing from 3.12±0.27 to 2.20±0.22 and anti-adhesion effectiveness increasing from 21.61%to 44.72%.Mechanistically,the abundant C=O bond functional groups on the surface of DLC can reduce reactive oxygen species level effectively;thus,the phosphorylation of NF-κB and M1 polarization of macrophages are inhibited.Consequently,excessive inflammatory response augmented by M1 macrophage-originated cytokines including interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-α(TNF-α)is largely reduced.For biocompatibility evaluation,PLA/DLC membrane is slowly absorbed within tissue and displays prolonged barrier effects compared to traditional PLA membranes.Further studies show the DLC depositing decelerates the release of degradation product lactic acid and its induction of macrophage M2 polarization by interfering esterase and PLA ester bonds,which further delays the fibrosis process.It was found that the PLA/DLC membrane possess an efficient biophysical mechanism for treatment of peritendinous adhesion.

Virtual orthopedic assessment:Main principles and specific regions

Telemedicine was originally created as a way to treat patients who were located in remote places far away from local health facilities or in areas with shortages of medical professionals.Telemedicine is still used today to address those problems,and is increasingly becoming a tool for convenient medical care.With the emergence of pandemics,telemedicine became almost a mandatory and valuable option for continuing to provide medical care in various specialties.As the threat of pandemic progress has continued for months and may continue for years,it is essential to validate existing tools to maintain clinical assessment and patient treatment to avoid negative consequences of the lack of medical follow-up.Therefore,the establishment of a virtual assessment technique that can be conducted effectively is of outmost importance as a way of adapting to the current situation.This study evaluated the role of telemedicine in the assessment of various orthopedic pathologies by means of a systematic virtual evaluation.

Total Hip Replacement: Short- and Medium-Term Morbidity and Mortality in the Department of Orthopedic Traumatology of Donka University Hospital, Guinea-Conakry

Introduction: Total hip prostheses are a reliable means of treating hip disorders. It is indicated when pain and reduced mobility of the hip become incompatible with the patient’s daily activities. In low-income countries, the risk factors for hip disease are numerous, but the means for its management, such as total hip prostheses, are not. The aim of this work was to determine the morbi-mortality of total hip prostheses in the short and medium term in our department and to review the literature. Patients and Method: This was a prospective and descriptive study over a period of 9 years. It involved 50 THPs performed on 45 patients. Patients who had received a THP and were followed up for at least two years were included. We excluded patients who were lost to follow-up. The Moore-type posterolateral minimally invasive approach was used. Complications were investigated from the immediate postoperative period and in the medium term. The final functional results were evaluated according to the Postel Merle d’Aubigné score. Results: We performed 50 THPs out of 750 procedures, i.e. , 6.6%. The indications were: primary coxarthrosis 60%, necrosis of the femoral head 26%, post-infectious balloon hip 4%, and pseudarthrosis of the femoral neck 10%. The average time to the consultation was 2.4 years with extremes of 1 and 5 years. According to the terrain, sickle cell disease represented 18%, tuberculosis 12%. Postoperative complications were lameness 12%, dislocation 6%, suppuration 6%, death 4%, peri-prosthetic fracture 8%, loosening 2%, peri-articular ossification 2%, and paralysis of the external popliteal nerve 2%. Conclusion: Whoever performs a THP is obliged to monitor the patient as long as he/she is alive. Complications are possible at any time and can negatively change the assigned goal and force the surgeon to be expensive and sometimes inconclusive secondary interventions.

Effects of individual shock wave therapy vs celecoxib on hip pain caused by femoral head necrosis

BACKGROUND Celecoxib has been used to treat hip discomfort and functional difficulties associated with osteonecrosis of the femoral head(ONFH),although significant adverse reactions often follow long-term use.Extracorporeal shock wave therapy(ESWT)can delay the progression of ONFH,alleviate the pain and functional limitations it causes,and avoid the adverse effects of celecoxib.AIM To investigate the effects of individual ESWT,a treatment alternative to the use of celecoxib,in alleviating pain and dysfunction caused by ONFH.METHODS This was a randomized,controlled,double-blinded,non-inferiority trial.We examined 80 patients for eligibility in this study;8 patients were excluded based on inclusion and exclusion criteria.A total of 72 subjects with ONFH were randomly assigned to group A(n=36;celecoxib+alendronate+sham-placebo shock wave)or group B(n=36;individual focused shock wave[ESWT based on magnetic resonance imaging three-dimensional(MRI-3D)reconstruction]+alendronate).The outcomes were assessed at baseline,at the end of treatment,and at an 8-wk follow-up.The primary outcome measure was treatment efficiency after 2 wk of intervention using the Harris hip score(HHS)(improvement of 10 points or more from the baseline was deemed sufficient).Secondary outcome measures were post-treatment HHS,visual analog scale(VAS),and Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)scores.RESULTS After treatment,the pain treatment efficiency of group B was greater than that of group A(69%vs 51%;95%CI:4.56%to 40.56%),with non-inferiority thresholds of-4.56%and-10%,respectively.Furthermore,the HHS,WOMAC,and VAS scores in group B dramatically improved during the follow-up period as compared to those in group A(P<0.001).After therapy,the VAS and WOMAC in group A were significantly improved from the 2nd to 8th wk(P<0.001),although HHS was only significantly altered at the 2 wk point(P<0.001).On the 1st d and 2nd wk after treatment,HHS and VAS scores were different between groups,with the difference in HHS lasting until week 4.Neither group had severe complications such as skin ulcer infection or lower limb motorsensory disturbance.CONCLUSION Individual shock wave therapy(ESWT)based on MRI-3D reconstruction was not inferior to celecoxib in managing hip pain and restrictions associated with ONFH.

Ferroptosis inhibition protects vascular endothelial cells and maintains integrity of the blood-spinal cord barrier after spinal cord injury

Maintaining the integrity of the blood-spinal cord barrier is critical for the recove ry of spinal cord injury.Ferro ptosis contributes to the pathogenesis of spinal cord injury.We hypothesized that ferroptosis is involved in disruption of the blood-s pinal cord barrier.In this study,we administe red the ferroptosis inhibitor liproxstatin-1 intraperitoneally after contusive spinal co rd injury in rats.Liproxstatin-1 improved locomotor recovery and somatosensory evoked potential electrophysiological performance after spinal cord inju ry.Liproxstatin-1 maintained blood-spinal cord barrier integrity by upregulation of the expression of tight junction protein.Liproxstatin-1 inhibited ferroptosis of endothelial cell after spinal cord injury,as shown by the immunofluorescence of an endothelial cell marker(rat endothelium cell antigen-1,RECA-1) and fe rroptosis markers Acyl-CoA synthetase long-chain family member 4 and 15-lipoxygenase.Liproxstatin-1reduced brain endothelial cell ferroptosis in vitro by upregulating glutathione peroxidase 4 and downregulating Acyl-CoA synthetase long-chain family member4 and 15-lipoxygenase.Furthermore,inflammatory cell recruitment and astrogliosis were mitigated after liproxstatin-1 treatment.In summary,liproxstatin-1im proved spinal cord injury recovery by inhibiting ferroptosis in endothelial cells and maintaining blood-s pinal co rd barrier integrity.

Neglected and Relapsed Clubfoot in Adults, the Functional Outcome of Acute Surgical Correction

Background: Neglected clubfoot in this series is defined as untreated equino-cavo-adducto-varus in older children or adults. Relapsed clubfoot is the residual deformity that remains after single or multiple surgical interventions. Severely neglected clubfoot rarely exists today in developed countries, except in some emigrants from low- and middle-income countries. Acute surgical management with corrective mid-foot osteotomy and elongation of the Achilles tendon has an excellent functional outcome. Objective: To assess the functional outcome of acute correction of neglected Talipes-quinoa-varus deformity in adults. Methods: This is a cross-sectional, hospital–based multi-centric study. Forty patients were included in this study. Midfoot osteotomy and elongation of the Achilles tendon were performed on all patients. Data was collected using a questionnaire and the functional outcome has been assessed using the American Orthopedic Foot and Ankle Society Score (AOFAS). This score was measured before surgery and one year after surgery. Results: the mean age was 19.9 ± 4.7 years. Males were 25 (62.5%) and females were 15 (37.5%). The mean preoperative AOFAS score was 37.7 ± 7.1 (poor). This score improved to 80.7 ± 13.7 (good to excellent), two years after surgery. However, this indicates a significant change in the functional outcome after the operation (p value Conclusion: acute correction of neglected and relapsed TEV with elongation of the Achilles tendon and single midfoot osteotomy has excellent functional outcome as assessed by AOFAS Score. The satisfaction with this procedure is impressive. The younger age population showed better outcomes with this procedure.

Regulatory role of NFAT1 signaling in articular chondrocyteactivities and osteoarthritis pathogenesis

Osteoarthritis (OA), the most common form of joint disease, is characterized clinically by joint pain, stiffness,and deformity. OA is now considered a whole joint disease;however, the breakdown of the articular cartilage remains themajor hallmark of the disease. Current treatments targeting OA symptoms have a limited impact on impeding orreversing the OA progression. Understanding the molecular and cellular mechanisms underlying OA development isa critical barrier to progress in OA therapy. Recent studies by the current authors’ group and others have revealedthat the nuclear factor of activated T cell 1 (NFAT1), a member of the NFAT family of transcription factors, regulatesthe expression of many anabolic and catabolic genes in articular chondrocytes of adult mice. Mice lacking NFAT1exhibit normal skeletal development but display OA in both appendicular and spinal facet joints as adults. Thisreview mainly focuses on the recent advances in the regulatory role of NFAT1 transcription factor in the activities ofarticular chondrocytes and its implication in the pathogenesis of OA.

Post-traumatic cauda equina nerve calcification:A case report

BACKGROUND Post-traumatic cauda equina nerve calcification is extremely rare in clinical practice,and its etiology,pathogenesis,treatment and prognosis are unclear.There are few studies and reports on Post-traumatic cauda equina nerve calci-fication,and this review reports a case of Post-traumatic cauda equina nerve calcification for reference.CASE SUMMARY A 52-year-old patient presented to our hospital with a history of lumbar spinal stenosis and a lumbar vertebral fracture caused by trauma.The patient's right lower limb had weakness in hip flexion,knee extension and plantarflexion with muscle strength grade 3,right ankle dorsiflexion and thumb dorsiflexion with muscle strength grade 0.The patient's skin sensation below the right knee plane disappeared.The patient's Computed tomography(CT)data showed signs of cauda equina nerve calcification and the terminal filaments in the plane of the third to fifth lumbar vertebrae.After treatment the patient's symptoms were slightly relieved.CONCLUSION We provide an extremely rare case of Post-traumatic cauda equina nerve calcification and offer a conservative treatment plan.However,the etiology,mechanism and treatment of Post-traumatic cauda equina nerve calcification are still unclear.This requires scholars to conduct more research and exploration in this area.

Effect of small interference RNA on expression of the Skp2 in human chondrocytes cell

Objective:To study the inhibitory effect of siRNA mediated by expression vectors on Skp2 expression in human chondrocytes.Method:Three Skp2 sequences siRNA-59,siRNA-318 and siRNA-504 were designed as target sites using online siRNA design tools.Skp2 siRNA expression vectors were successfully constructed in vitro by gene recombination technology,and the influence of recombinant plasmid transfection on Skp2 mRNA expression was detected.DNA electrophoresis was used to verify the results.Results:The sequence of Skp2 interference was correct by sequence analysis.The expression of Skp2 mRNA in siRNA-59,siRNA-318,siRNA-504 transfection group was significantly lower than that in no-load group and NC group(P<0.05),the inhibition rates of Skp2 mRNA in siRNA-59,siRNA-318 and siRNA-504 were respectively 60%,41%and 64%,and the siRNA-504 transfection group had the highest inhibition rate.Conclusion:The siRNA eukaryotic expression vector of Skp2 gene was constructed successfully which effectively inhibit Skp2 mRNA expression in human chondrocytes cell,and can provide strong evidence for the treatment of osteoarthritis.