CD47 is a ubiquitous and pleiotropic cell-surface receptor.Disrupting CD47 enhances injury repair in various tissues but the role of CD47 has not been studied in bone injuries.In a murine closed-fracture model,CD47-nu...CD47 is a ubiquitous and pleiotropic cell-surface receptor.Disrupting CD47 enhances injury repair in various tissues but the role of CD47 has not been studied in bone injuries.In a murine closed-fracture model,CD47-null mice showed decreased callus bone formation as assessed by microcomputed tomography 10 days post-fracture and increased fibrous volume as determined by histology.To understand the cellular basis for this phenotype,mesenchymal progenitors(MSC)were harvested from bone marrow.CD47-null MSC showed decreased large fibroblast colony formation(CFU-F),significantly less proliferation,and fewer cells in Sphase,although osteoblast differentiation was unaffected.However,consistent with prior research,CD47-null endothelial cells showed increased proliferation relative to WT cells.Similarly,in a murine ischemic fracture model,CD47-null mice showed reduced fracture callus size due to a reduction in bone relative to WT 15 days-post fracture.Consistent with our in vitro results,in vivo EdU labeling showed decreased cell proliferation in the callus of CD47-null mice,while staining for CD31 and endomucin demonstrated increased endothelial cell density.Finally,WT mice with ischemic fracture that were administered a CD47 morpholino,which blocks CD47 protein production,showed a callus phenotype similar to that of ischemic fractures in CD47-null mice,suggesting the phenotype was not due to developmental changes in the knockout mice.Thus,inhibition of CD47 during bone healing reduces both non-ischemic and ischemic fracture healing,in part,by decreasing MSC proliferation.Furthermore,the increase in endothelial cell proliferation and early blood vessel density caused by CD47 disruption is not sufficient to overcome MSC dysfunction.展开更多
Repairing the endothelial barrier is essential for maintaining pulmonary fuid balance and regulating leukocyte infiltration during sepsis[1].Tissue kallikrein-related peptidases(KLKs)are secreted serine proteases invo...Repairing the endothelial barrier is essential for maintaining pulmonary fuid balance and regulating leukocyte infiltration during sepsis[1].Tissue kallikrein-related peptidases(KLKs)are secreted serine proteases involved in angiogenesis[2].However,their involvement in regulating endothelial regeneration remains largely unknown.展开更多
The global demand for effective skin injury treatments has prompted the exploration of tissue engineering solutions.While three-dimensional(3D)bioprinting has shown promise,challenges persist with respect to achieving...The global demand for effective skin injury treatments has prompted the exploration of tissue engineering solutions.While three-dimensional(3D)bioprinting has shown promise,challenges persist with respect to achieving timely and compatible solutions to treat diverse skin injuries.In situ bioprinting has emerged as a key new technology,since it reduces risks during the implantation of printed scaffolds and demonstrates superior therapeutic effects.However,maintaining printing fidelity during in situ bioprinting remains a critical challenge,particularly with respect to model layering and path planning.This study proposes a novel optimization-based conformal path planning strategy for in situ bioprinting-based repair of complex skin injuries.This strategy employs constrained optimization to identify optimal waypoints on a point cloud-approximated curved surface,thereby ensuring a high degree of similarity between predesigned planar and surface-mapped 3D paths.Furthermore,this method is applicable for skin wound treatments,since it generates 3D-equidistant zigzag curves along surface tangents and enables multi-layer conformal path planning to facilitate the treatment of volumetric injuries.Furthermore,the proposed algorithm was found to be a feasible and effective treatment in a murine back injury model as well as in other complex models,thereby showcasing its potential to guide in situ bioprinting,enhance bioprinting fidelity,and facilitate improvement of clinical outcomes.展开更多
Successful polyethylene glycol fusion(PEG-fusion)of severed axons following peripheral nerve injuries for PEG-fused axons has been reported to:(1)rapidly restore electrophysiological continuity;(2)prevent distal Walle...Successful polyethylene glycol fusion(PEG-fusion)of severed axons following peripheral nerve injuries for PEG-fused axons has been reported to:(1)rapidly restore electrophysiological continuity;(2)prevent distal Wallerian Degeneration and maintain their myelin sheaths;(3)promote primarily motor,voluntary behavioral recoveries as assessed by the Sciatic Functional Index;and,(4)rapidly produce correct and incorrect connections in many possible combinations that produce rapid and extensive recovery of functional peripheral nervous system/central nervous system connections and reflex(e.g.,toe twitch)or voluntary behaviors.The preceding companion paper describes sensory terminal field reo rganization following PEG-fusion repair of sciatic nerve transections or ablations;howeve r,sensory behavioral recovery has not been explicitly explored following PEG-fusion repair.In the current study,we confirmed the success of PEG-fusion surgeries according to criteria(1-3)above and more extensively investigated whether PEG-fusion enhanced mechanical nociceptive recovery following sciatic transection in male and female outbred Sprague-Dawley and inbred Lewis rats.Mechanical nociceptive responses were assessed by measuring withdrawal thresholds using von Frey filaments on the dorsal and midplantar regions of the hindpaws.Dorsal von Frey filament tests were a more reliable method than plantar von Frey filament tests to assess mechanical nociceptive sensitivity following sciatic nerve transections.Baseline withdrawal thresholds of the sciatic-mediated lateral dorsal region differed significantly across strain but not sex.Withdrawal thresholds did not change significantly from baseline in chronic Unoperated and Sham-operated rats.Following sciatic transection,all rats exhibited severe hyposensitivity to stimuli at the lateral dorsal region of the hindpaw ipsilateral to the injury.However,PEG-fused rats exhibited significantly earlier return to baseline withdrawal thresholds than Negative Control rats.Furthermore,PEG-fused rats with significantly improved Sciatic Functional Index scores at or after 4 weeks postoperatively exhibited yet-earlier von Frey filament recove ry compared with those without Sciatic Functional Index recovery,suggesting a correlation between successful PEG-fusion and both motor-dominant and sensory-dominant behavioral recoveries.This correlation was independent of the sex or strain of the rat.Furthermore,our data showed that the acceleration of von Frey filament sensory recovery to baseline was solely due to the PEG-fused sciatic nerve and not saphenous nerve collateral outgrowths.No chronic hypersensitivity developed in any rat up to 12 weeks.All these data suggest that PEG-fusion repair of transection peripheral nerve injuries co uld have important clinical benefits.展开更多
BACKGROUND Meniscal tears are one of the most common knee injuries.After the diagnosis of a meniscal tear has been made,there are several factors physicians use to guide clinical decision-making.The influence of time ...BACKGROUND Meniscal tears are one of the most common knee injuries.After the diagnosis of a meniscal tear has been made,there are several factors physicians use to guide clinical decision-making.The influence of time between injury and isolated meniscus repair on patient outcomes is not well described.Assessing this relationship is important as it may influence clinical decision-making and can add to the preoperative patient education process.We hypothesized that increasing the time from injury to meniscus surgery would worsen postoperative outcomes.AIM To investigate the current literature for data on the relationship between time between meniscus injury and repair on patient outcomes.METHODS PubMed,Academic Search Complete,MEDLINE,CINAHL,and SPORTDiscus were searched for studies published between January 1,1995 and July 13,2023 on isolated meniscus repair.Exclusion criteria included concomitant ligament surgery,incomplete outcomes or time to surgery data,and meniscectomies.Patient demographics,time to injury,and postoperative outcomes from each study were abstracted and analyzed.RESULTS Five studies met all inclusion and exclusion criteria.There were 204(121 male,83 female)patients included.Three of five(60%)studies determined that time between injury and surgery was not statistically significant for postoperative Lysholm scores(P=0.62),Tegner scores(P=0.46),failure rate(P=0.45,P=0.86),and International Knee Documentation Committee scores(P=0.65).Two of five(40%)studies found a statistically significant increase in Lysholm scores with shorter time to surgery(P=0.03)and a statistically significant association between progression of medial meniscus extrusion ratio(P=0.01)and increasing time to surgery.CONCLUSION Our results do not support the hypothesis that increased time from injury to isolated meniscus surgery worsens postoperative outcomes.Decision-making primarily based on injury interval is thus not recommended.展开更多
The exchange of information and materials between organelles plays a crucial role in regulating cellular physiological functions and metabolic levels.Mitochondria-associated endoplasmic reticulum membranes serve as ph...The exchange of information and materials between organelles plays a crucial role in regulating cellular physiological functions and metabolic levels.Mitochondria-associated endoplasmic reticulum membranes serve as physical contact channels between the endoplasmic reticulum membrane and the mitochondrial outer membrane,formed by various proteins and protein complexes.This microstructural domain mediates several specialized functions,including calcium(Ca^(2+))signaling,autophagy,mitochondrial morphology,oxidative stress response,and apoptosis.Notably,the dysregulation of Ca^(2+)signaling mediated by mitochondria-associated endoplasmic reticulum membranes is a critical factor in the pathogenesis of neurological diseases.Certain proteins or protein complexes within these membranes directly or indirectly regulate the distance between the endoplasmic reticulum and mitochondria,as well as the transduction of Ca^(2+)signaling.Conversely,Ca^(2+)signaling mediated by mitochondria-associated endoplasmic reticulum membranes influences other mitochondria-associated endoplasmic reticulum membraneassociated functions.These functions can vary significantly across different neurological diseases—such as ischemic stroke,traumatic brain injury,Alzheimer's disease,Parkinson's disease,amyotrophic lateral sclerosis,and Huntington's disease—and their respective stages of progression.Targeted modulation of these disease-related pathways and functional proteins can enhance neurological function and promote the regeneration and repair of damaged neurons.Therefore,mitochondria-associated endoplasmic reticulum membranes-mediated Ca^(2+)signaling plays a pivotal role in the pathological progression of neurological diseases and represents a significant potential therapeutic target.This review focuses on the effects of protein complexes in mitochondria-associated endoplasmic reticulum membranes and the distinct roles of mitochondria-associated endoplasmic reticulum membranes-mediated Ca^(2+)signaling in neurological diseases,specifically highlighting the early protective effects and neuronal damage that can result from prolonged mitochondrial Ca^(2+)overload or deficiency.This article provides a comprehensive analysis of the various mechanisms of Ca^(2+)signaling mediated by mitochondria-associated endoplasmic reticulum membranes in neurological diseases,contributing to the exploration of potential therapeutic targets for promoting neuroprotection and nerve repair.展开更多
The plasma membrane(PM)plays an essential role in maintaining cell homeostasis,therefore,timely and effective repair of damage caused by factors such as mechanical rupture,pore-forming toxins,or pore-forming proteins ...The plasma membrane(PM)plays an essential role in maintaining cell homeostasis,therefore,timely and effective repair of damage caused by factors such as mechanical rupture,pore-forming toxins,or pore-forming proteins is crucial for cell survival.PM damage induces membrane rupture and stimulates an immune response.However,damage resulting from regulated cell death processes,including pyroptosis,ferroptosis,and necroptosis,cannot be repaired by simple sealing mechanisms and thus,requires specialized repair machinery.Recent research has identified a PM repair mechanism of regulated cell death-related injury,mediated by the endosomal sorting complexes required for transport(ESCRT)machinery.Here,we review recent progress in elucidating the ESCRT machinery-mediated repair mechanism of PM injury,with particular focus on processes related to regulated cell death.This overview,along with continued research in this field,may provide novel insights into therapeutic targets for diseases associated with dysregulation of regulated cell death pathways.展开更多
BACKGROUND Rotator cuff tears are a chief cause of shoulder pain and disability,and surgical repair is often required when conservative management fails.As digital health technologies have expanded,especially since th...BACKGROUND Rotator cuff tears are a chief cause of shoulder pain and disability,and surgical repair is often required when conservative management fails.As digital health technologies have expanded,especially since the coronavirus disease 2019 pandemic,digitally augmented rehabilitation programs emerged as a potential alternative to conventional physical therapy.AIM To determine if digitally assisted rehabilitation could be as practical,or even more effective,than the traditional methods most patients currently follow.METHODS Six electronic databases,including PubMed,Scopus,Cochrane Library,Google Scholar,EMBASE,and Web of Science,were searched to find articles that compare digital-based rehabilitation and conventional treatment.Outcomes of interest were Disabilities of the Arm,Shoulder and Hand(DASH)score and range of motion.The quality assessment of the included studies was performed using the risk-of-bias tool for randomized trials tool.RESULTS Three randomized controlled trial studies were enrolled in this study,including 195 cases.We did not find any significant differences between the two groups in terms of DASH score,flexion range of motion,and external rotation range of motion.There was a significant difference between the two groups for abduction range of motion.CONCLUSION Digital home-based rehab seems to be a strong alternative to traditional methods,offering similar results for people recovering from rotator cuff surgery.This approach might also make rehab more accessible and engaging for patients.That said,further research is needed to fully understand the potential of digital rehabilitation and ensure it works effectively for everyone.展开更多
Objectives:To assess outcomes of rectourethral fistula repair utilizing a gracilis flap in a largely radiated cohort.Patients and Methods:We performed a retrospective review of all gracilis interposition flap reconstr...Objectives:To assess outcomes of rectourethral fistula repair utilizing a gracilis flap in a largely radiated cohort.Patients and Methods:We performed a retrospective review of all gracilis interposition flap reconstruction surgeries performed for RUF at a university hospital in South Carolina between January 2010 and June 2023.All repairs utilized a multidisciplinary approach with urology,colorectal,and plastic surgery teams.Postoperatively,patients were maximally drained with foley catheter and suprapubic tube(SPT).Initial voiding cystourethrogram(VCUG)was performed at 4 weeks post-repair.If there was a persistent leak,catheter drainage was maintained for 4 additional weeks and VCUG was repeated.Success was defined as absence of leak on VCUG within 3 months after surgery.Results:22 patients met inclusion criteria.68%of patients had history of external beam radiation therapy(EBRT),13.6%had brachytherapy,and 40.9%had cryotherapy.Initial post-operative VCUG was negative in 10 patients(45.5%).Of the 12 patients with a persistent fistula,5(42%)had no evidence of fistula on subsequent VCUG after 4 weeks.Overall,68%of patients were successfully treated with gracilis interposition flap.There was a significant difference of repair success based on EBRT status(p<0.05).Conclusions:We report a success rate of 68%for gracilis flap repair of RUF.Our cohort had a higher rate of prior radiation therapy compared to other studies.A clinically significant portion of patients with an initial positive VCUG will seal their fistula with prolonged catheter drainage.Gracilis interposition flap is a reasonable surgical treatment for RUF.展开更多
Osteochondral defects pose an enormous challenge,and no satisfactory therapy is available to date due to the hierarchy of the native tissue consisting of articular cartilage and subchondral bone.Constructing a scaffol...Osteochondral defects pose an enormous challenge,and no satisfactory therapy is available to date due to the hierarchy of the native tissue consisting of articular cartilage and subchondral bone.Constructing a scaffold with biological function and biomimetic structure is the key to achieving a high-quality repair effect.Herein,a natural polymer-based bilayer scaffold with a porous architecture similar to that of osteochondral tissue is designed,involving the transforming growth factor-beta3-liposome-loaded upper layer for superficial cartilage regeneration and the nanohydroxyapatite-coated lower layer for subchondral bone rehabilitation.This research is conducted to evaluate the effects of nanoparticle-modified bilayer scaffold to mimic the hierarchical pro-chondrogenic and proosteogenic microenvironment for the recruited endogenous bone marrow mesenchymal stem cells.The fabricated composites were evaluated for mechanical,physicochemical,biological properties,in vitro and in vivo tissue regeneration potential.Overall,the current bilayer scaffold could regenerate a cartilage-bone integrated tissue with a seamless interfacial integration and exhibited superior tissue repair outcomes compared to other single layer scaffolds based on morphological,radiological and histological evaluation,verifying that this novel graft could be an effective approach to tissue-engineered analogs of cartilage-subchondral bone and offer new therapeutic opportunities for osteochondral defect-associated diseases.展开更多
BACKGROUND Inguinal and umbilical hernias are common neonatal conditions.Open hernia repair is currently the primary surgical treatment,but postoperative recurrence remains a significant risk.AIM To identify the risk ...BACKGROUND Inguinal and umbilical hernias are common neonatal conditions.Open hernia repair is currently the primary surgical treatment,but postoperative recurrence remains a significant risk.AIM To identify the risk factors for recurrence following open neonatal hernia repair.METHODS We retrospectively reviewed the data of 56 neonates who underwent open hernia repair at Shijiazhuang Maternal and Child Health Hospital between March 2021 and December 2023.The patients were categorized into recurrence and non-recurrence groups based on their experience of postoperative recurrence.Uni-variate analysis was performed to examine various factors,and those with P<0.1 in univariate analysis were included in multivariate logistic regression.No-mogram models were constructed,and their performance was evaluated using receiver operating characteristic curves.RESULTS Of the 56 children,11(19.64%)experienced postoperative recurrence,whereas the remaining 45(80.36%)did not.Univariate analysis identified anemia(P=0.079),persistent postoperative pain(P=0.049),and low birth weight(P=0.017)as factors associated with recurrence.Multivariate logistic regression analysis re-vealed that anemia(P=0.029),persistent postoperative pain(P=0.008),and low birth weight(P=0.009)were independent risk factors for recurrence after open hernia repair in neonates.CONCLUSION The risk of recurrence after open hernia repair should be closely monitored in neonates with low birth weight,anemia,and persistent postoperative pain.展开更多
Arsenic(As)and chromium(Cr)are two harmful toxicants as well as carcinogens which can coexist in polluted surface water and groundwater.This coexistence leads to mixture effects in animals including fish.Both of these...Arsenic(As)and chromium(Cr)are two harmful toxicants as well as carcinogens which can coexist in polluted surface water and groundwater.This coexistence leads to mixture effects in animals including fish.Both of these heavy metals are reported to manifest reactive oxygen species(ROS)mediated toxicity.Though individual neurotoxic effects have been reported,their mixture effects,its mechanism and cellular responses against oxidative stress and DNA damages remain unknown.The present study evaluated the individual and mixture effects of As and Cr at their environmentally relevant concentrations in zebrafish(Danio rerio)brain after 15,30 and 60 days of exposure.Nrf2,a transcription factor is involved in the expressional regulation of enzymes needed to maintain cellular redox homeostasis.This study reported the expressional pattern of Nrf2 and its associated xenobiotic metabolizing enzyme Nqo1 and other markers of oxidative stress such as ROS generation,reduced glutathione level,lipid peroxidation and catalase activity.Increased malondialdehyde(MDA)content,glutathione level,and catalase activity indicated oxidative stress in exposed groups.In addition,this study revealed expressional alterations of neurotoxicity marker(ache),DNA repair(ogg1,apex1,creb1,polb,mlh1,msh2 and msh6)and tumor suppressor(p53,brca2)genes.Results of ROS generation,MDA level,histopathological analysis,gene expression and immunofluorescence study confirmed that As and Cr did not show antagonistic effects in combination rather indicated additive effects which was dose-dependent but not always linear.展开更多
BACKGROUND Transplantectomy has long been considered the preferred treatment for spontaneous renal graft rupture,prioritizing patient safety over kidney salvage.In the last decade,there has been an increasing number o...BACKGROUND Transplantectomy has long been considered the preferred treatment for spontaneous renal graft rupture,prioritizing patient safety over kidney salvage.In the last decade,there has been an increasing number of reports showing that,in selected scenarios,conservative management through graft repair represents a feasible option,challenging traditional approaches.CASE SUMMARY We describe the case of a 37-year-old sensitized XY patient who experienced early spontaneous graft rupture after receiving his second deceased donor kidney transplant.Following temporary hemodynamic stabilization and abdominal contrast enhanced computed tomography scan assessment,the recipient was brought back to theatre for surgical exploration.Possible causes of irreversible graft damage were immediately ruled out.The fractured upper pole of the transplanted kidney was repaired using a fibrin sealant,external compression,and a tailored polyglactin 910 mesh wrapped around the graft.The post-operative course was uneventful.After 20 months of follow up,the patient is doing very well,with excellent renal function and complete reabsorption of the mesh,as demonstrated by serial ultrasound evaluations of the graft.CONCLUSION Amid organ shortages and sensitized patients,graft nephrectomy is reserved for severe injuries;repair using sealants and mesh is effective.展开更多
BACKGROUND Long head of biceps tendon(LHBT)transposition is a novel technique based on the double-row suture bridge method,utilizing autologous reconstruction to treat massive rotator cuff tears.AIM To evaluate the mi...BACKGROUND Long head of biceps tendon(LHBT)transposition is a novel technique based on the double-row suture bridge method,utilizing autologous reconstruction to treat massive rotator cuff tears.AIM To evaluate the mid-to-long-term clinical outcomes following the double-row repair method for massive rotator cuff tears.METHODS This retrospective analysis included data from 53 patients with massive rotator cuff tears treated at our hospital between 2020 and 2021.The patients were divided into the double-row repair group(conventional group)and the doublerow repair combined with the LHBT transposition group(transposition group).Postoperative pain was assessed using the visual analogue scale at one week,one year,and the final follow-up.Shoulder function was evaluated using the American Shoulder and Elbow Surgeons and Constant-Murley scores at one year and the final follow-up.Rotator cuff healing was assessed postoperatively for one year using the Sugaya classification,which categorizes tendon integrity based on magnetic resonance imaging findings.RESULTS No perioperative complications were observed in any of the patients at any time.There were no significant differences between the groups regarding operative time and intraoperative blood loss.The transposition group had significantly lower visual analogue scale scores than the conventional group at one week postoperatively;however,there were no significant differences between the groups at one year or the final follow-up.At one year postoperatively,the transposition group showed significantly higher American Shoulder and Elbow Surgeons and Constant-Murley scores than the conventional group;no significant differences were observed at the final followup.There were no significant differences in rotator cuff healing between the groups at one year postoperatively.CONCLUSION Compared to double-row repair alone,double-row repair combined with LHBT transposition for treating massive rotator cuff tears more effectively alleviates short-term postoperative pain and improves shoulder function within the first year.展开更多
BACKGROUND Incisional hernia(IH)is a common complication following liver transplantation(LT),contributing to significant morbidity and impaired quality of life.The interplay of transplant-specific factors,patient como...BACKGROUND Incisional hernia(IH)is a common complication following liver transplantation(LT),contributing to significant morbidity and impaired quality of life.The interplay of transplant-specific factors,patient comorbidities,surgical complexity,and immunosuppression presents considerable challenges in hernia repair,often accompanied by substantial risks.AIM To assess the incidence,risk factors,and outcomes of IH repair in LT recipients.METHODS A systematic literature search was conducted across MEDLINE,EMBASE,Scopus,CINAHL,the Cochrane Library,Google Scholar,and PubMed,yielding 493 results.In accordance with PRISMA guidelines,39 studies reporting on IH following LT were included in the final analysis.Studies involving paediatric populations,hernias unrelated to transplant incisions,living liver donors,non-LT,and multiorgan transplants were excluded.Meta-analysis was performed using Cochrane RevMan software.The study has been registered with PROSPERO(CRD420-24563398).RESULTS A review of 39 studies revealed incidence of post-LT IH ranging from 1.7%to upto 42.8%.Pooled analysis showed comparable demographics among groups and post-LT IH incidence was higher in older age recipients[mean difference(MD)=2.39,95%CI:1.15-3.63,P<0.001],male gender(relative risk=1.42,95%CI:1.18-1.72,P<0.001),high body mass index(BMI)(MD=1.06,95%CI:0.82-1.29,P<0.001),Mercedez-Benz incision type[odds ratio(OR)=0.45,95%CI:0.21,0.96,P=0.04],and need for re-laparotomy(OR=2.49,95%CI:1.05-5.93,P=0.04).No significant differences were found in recurrence rates or wound complications between open and laparoscopic IH repairs.CONCLUSION Older recipient age,male gender,high BMI,Mercedes-Benz incision,and re-laparotomy after LT are significant risk factors for IH.In contrast,model for end-stage liver disease score,pre-LT ascites,acute rejection,and mammalian target of rapamycin inhibitor therapy do not appear to influence IH development.While open repair remains the predominant approach post-LT,no significant differences in recurrence or wound complication rates have been observed between open and laparoscopic repairs.However,open repair is associated with a shorter operative time.展开更多
The article explains the legal definition of the term‘repair’as used in cosmetic efficacy claims:it refers to the ability to help maintain the normal condition of the applied area.By analysing methods for modelling ...The article explains the legal definition of the term‘repair’as used in cosmetic efficacy claims:it refers to the ability to help maintain the normal condition of the applied area.By analysing methods for modelling skin damage,the paper comprehensively summarises the evaluation system for the‘repair’efficacy of cosmetics,introducing existing assessment methods for repair efficacy across different application areas,including facial care products,body care products,foot care products,scalp care products,hair care products,and lip care products.This aims to promote the standardisation and innovative development of repair-type cosmetics.展开更多
Exosomes derived from bone mesenchymal stem cells(BMSCs)show promising potential for treating bone defects.However,their clinical application is hindered by low yield and insufficient repair ability.Three-dimensional(...Exosomes derived from bone mesenchymal stem cells(BMSCs)show promising potential for treating bone defects.However,their clinical application is hindered by low yield and insufficient repair ability.Three-dimensional(3D)mechanical stimulation has been a well-known method for enhancing exosome secretion;however,the traditional stimulation process is always achieved by controlling the displacement of manipulators,which may induce uneven loading distribution and degradation of stimulation strength.Here,we propose a micro-stretching manipulator that automatically controls the stretching force applied to gelatin methacryloyl(GelMA)/hyaluronic acid methacryloyl(HAMA)hybrid hydrogel sheets containing BMSCs within an incubator.To ensure the structural stability of the sheets after long-term stretching,the mixing ratio between GelMA and HAMA was optimized according to the mechanical property response of the sheets to cyclical loading.Subsequently,force-controlled mechanical loading was applied to the BMSC-laden sheets to produce exosomes.Compared with displacement control,force-controlled loading provides a more stable force stimulation,thereby enhancing exosome secretion.Furthermore,continuously stimulated exosomes exhibited a stronger capacity for promoting osteogenic differentiation of BMSCs and facilitating the repair of bone defects in a rat model.These findings suggest that force-controlled loading of cell-laden hydrogels offers a novel approach for the production of BMSC-derived exosomes and their application in bone repair.展开更多
BACKGROUND The presence of a large paraesophageal hernia is a source of concern in foregut surgery.Thus,scholars have focused on ascertaining the optimal surgical approach,methods for reinforcing the esophageal hiatus...BACKGROUND The presence of a large paraesophageal hernia is a source of concern in foregut surgery.Thus,scholars have focused on ascertaining the optimal surgical approach,methods for reinforcing the esophageal hiatus,and strategies for preventing hernia recurrence and gastroesophageal reflux.AIM To investigate the outcomes of surgery for giant paraesophageal hernias without sac removal.METHODS Sixty-six consecutive patients who underwent surgery for a giant paraesophageal hernia between May 2010 and December 2024 were included in this retrospective study.The pre-and postoperative examinations included upper gastrointestinal endoscopy,X-ray with barium contrast swallow,contrast-enhanced computed tomography(CT)scans of the chest and abdomen,24-hour potential hydrogen esophageal monitoring,and esophagomanometry.The study group included 36 patients who underwent surgery without sac removal,and the control group included 30 patients who underwent surgery with sac removal.RESULTS Fifty-two patients(28 in the study group and 24 in the control group)underwent laparoscopic procedures,10(6 in the study group and 4 in the control group)underwent open procedures,and 4(2 in each group)underwent conversion procedures.The operative time and postoperative length of stay were significantly longer in the control group than in the study group.In 12 patients in the study group,X-ray examination on postoperative days 3-5 revealed air-fluid levels at the site of the remaining hernia sac;all air-fluid levels disappeared without intervention 2 months later.Postoperative day 60 CT and X-ray examinations revealed no pathological changes related to the hernia sac in the mediastinum.CONCLUSION Removal of the hernia sac during surgery for giant paraesophageal hernias is not mandatory.Further large-scale multicentric randomized trials are needed for a more detailed investigation in this field.展开更多
The accumulation of deoxyribonucleic acid(DNA)oxidative damage mediated by reactive oxygen species(ROS)is closely associated with liver diseases.8-Oxoguanine(8-OxoG),a prevalent DNA oxidation product,plays a significa...The accumulation of deoxyribonucleic acid(DNA)oxidative damage mediated by reactive oxygen species(ROS)is closely associated with liver diseases.8-Oxoguanine(8-OxoG),a prevalent DNA oxidation product,plays a significant role in liver disease progression.The base excision repair(BER)pathway,comprising over 30 proteins including 8-OxoG DNA glycosylase1(OGG1),MutY homolog(MUTYH),and MutT homolog protein 1(MTH1),is responsible for the clearance and mismatch repair of 8-OxoG.Abnormally high levels of 8-OxoG and dysregulated expression and function of 8-OxoG repair enzymes contribute to the onset and development of liver diseases.Consequently,targeting the 8-OxoG production and repair system with agonists or inhibitors may offer a promising approach to liver disease treatment.This review summarizes the impact of 8-OxoG accumulation and dysregulated repair enzymes on various liver diseases,including viral liver disease,alcoholic liver disease(ALD),metabolic dysfunction-associated steatotic liver disease(MASLD),cholestatic liver disease(CLD),liver fibrosis,cirrhosis,and liver cancer.Additionally,we review natural constituents as potential therapeutic agents that regulate 8-OxoG production,repair enzymes,and repair system-related signal pathways in oxidative damage-induced liver diseases.展开更多
Adipocyte-secreted extracellular vesicles(EVs)and adipose-derived stem cells(ADSCs)regulate physiological and pathological processes by delivering nucleic acids,proteins,and lipids.Both adipocyte-and ADSC-derived EVs ...Adipocyte-secreted extracellular vesicles(EVs)and adipose-derived stem cells(ADSCs)regulate physiological and pathological processes by delivering nucleic acids,proteins,and lipids.Both adipocyte-and ADSC-derived EVs regulate local inflammatory levels,tumor progression,and insulin sensitivity.These two types of EVs also have significant therapeutic effects on damage repair,including wound healing,angiogenesis,myocardial damage,vessel re-endothelialization,bone and cartilage regeneration,muscle repair,and nerve repair.With regard to wound healing,microRNA-21,microRNA-126,microRNA-31,and long non-coding RNA-H19 accelerate the proliferation and migration of fibroblasts,human immortalized keratinocytes,and endothelial cells via the PI3K/Akt/ERK pathway or fibrillin 1.ADSC-derived EVs contain various growth factors that are beneficial for wound healing.Numerous miRNAs in ADSC-derived EVs and β3-adrenergic receptors on brown adipocytes exhibit protective effects against myocardial infarction.Proteins in adipocyte-and ADSC-derived EVs play a role in promoting vessel re-endothelialization and regulating vasodilation.Angiogenesis is beneficial for the regeneration and repair of injured bone,cartilage,muscle,and nerves.Compared with adipocyte EVs,ADSC-EVs contain a greater variety of miRNAs and proteins that promote tissue regeneration.EV therapy is a promising cell-free therapy,and EV-loaded materials have been used for wound healing and myocardial damage.Future research will focus on identifying the molecules in EVs and the repair mechanisms that contribute to damage repair and regeneration.In addition,we aim to discover materials designed for slow release and specificity to facilitate tissue repair and optimize EV transportation.展开更多
基金supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases(NIAMS)of the National Institutes of Health(NIH)under award numbers F30AR071201(R.L.Z.)and R01 AR066028(K.D.H.)Additional research support is provided by the NIH under a training award T32TR004371(C.A.C.).
文摘CD47 is a ubiquitous and pleiotropic cell-surface receptor.Disrupting CD47 enhances injury repair in various tissues but the role of CD47 has not been studied in bone injuries.In a murine closed-fracture model,CD47-null mice showed decreased callus bone formation as assessed by microcomputed tomography 10 days post-fracture and increased fibrous volume as determined by histology.To understand the cellular basis for this phenotype,mesenchymal progenitors(MSC)were harvested from bone marrow.CD47-null MSC showed decreased large fibroblast colony formation(CFU-F),significantly less proliferation,and fewer cells in Sphase,although osteoblast differentiation was unaffected.However,consistent with prior research,CD47-null endothelial cells showed increased proliferation relative to WT cells.Similarly,in a murine ischemic fracture model,CD47-null mice showed reduced fracture callus size due to a reduction in bone relative to WT 15 days-post fracture.Consistent with our in vitro results,in vivo EdU labeling showed decreased cell proliferation in the callus of CD47-null mice,while staining for CD31 and endomucin demonstrated increased endothelial cell density.Finally,WT mice with ischemic fracture that were administered a CD47 morpholino,which blocks CD47 protein production,showed a callus phenotype similar to that of ischemic fractures in CD47-null mice,suggesting the phenotype was not due to developmental changes in the knockout mice.Thus,inhibition of CD47 during bone healing reduces both non-ischemic and ischemic fracture healing,in part,by decreasing MSC proliferation.Furthermore,the increase in endothelial cell proliferation and early blood vessel density caused by CD47 disruption is not sufficient to overcome MSC dysfunction.
基金supported by the National Natural Science Foundation of China(Grant Nos.:32171124,31871156,31971101,32271180,82272229,and 81471852)Hunan Provincial Natural Science Foundation of China(Grant No.:2021JJ31058).
文摘Repairing the endothelial barrier is essential for maintaining pulmonary fuid balance and regulating leukocyte infiltration during sepsis[1].Tissue kallikrein-related peptidases(KLKs)are secreted serine proteases involved in angiogenesis[2].However,their involvement in regulating endothelial regeneration remains largely unknown.
基金supported in part by the National Natural Science Foundation of China(Nos.52205532 and 624B2077)the National Key Research and Development Program of China(No.2023YFB4302003).
文摘The global demand for effective skin injury treatments has prompted the exploration of tissue engineering solutions.While three-dimensional(3D)bioprinting has shown promise,challenges persist with respect to achieving timely and compatible solutions to treat diverse skin injuries.In situ bioprinting has emerged as a key new technology,since it reduces risks during the implantation of printed scaffolds and demonstrates superior therapeutic effects.However,maintaining printing fidelity during in situ bioprinting remains a critical challenge,particularly with respect to model layering and path planning.This study proposes a novel optimization-based conformal path planning strategy for in situ bioprinting-based repair of complex skin injuries.This strategy employs constrained optimization to identify optimal waypoints on a point cloud-approximated curved surface,thereby ensuring a high degree of similarity between predesigned planar and surface-mapped 3D paths.Furthermore,this method is applicable for skin wound treatments,since it generates 3D-equidistant zigzag curves along surface tangents and enables multi-layer conformal path planning to facilitate the treatment of volumetric injuries.Furthermore,the proposed algorithm was found to be a feasible and effective treatment in a murine back injury model as well as in other complex models,thereby showcasing its potential to guide in situ bioprinting,enhance bioprinting fidelity,and facilitate improvement of clinical outcomes.
基金supported by DOD AFIRMⅢW81XWH-20-2-0029 subcontract,UT POC19-1774-13Neuraptive Therapeutics Inc.26-7724-56+1 种基金NIH R01-NS128086 grantsLone Star Paralysis gift(to GDB)。
文摘Successful polyethylene glycol fusion(PEG-fusion)of severed axons following peripheral nerve injuries for PEG-fused axons has been reported to:(1)rapidly restore electrophysiological continuity;(2)prevent distal Wallerian Degeneration and maintain their myelin sheaths;(3)promote primarily motor,voluntary behavioral recoveries as assessed by the Sciatic Functional Index;and,(4)rapidly produce correct and incorrect connections in many possible combinations that produce rapid and extensive recovery of functional peripheral nervous system/central nervous system connections and reflex(e.g.,toe twitch)or voluntary behaviors.The preceding companion paper describes sensory terminal field reo rganization following PEG-fusion repair of sciatic nerve transections or ablations;howeve r,sensory behavioral recovery has not been explicitly explored following PEG-fusion repair.In the current study,we confirmed the success of PEG-fusion surgeries according to criteria(1-3)above and more extensively investigated whether PEG-fusion enhanced mechanical nociceptive recovery following sciatic transection in male and female outbred Sprague-Dawley and inbred Lewis rats.Mechanical nociceptive responses were assessed by measuring withdrawal thresholds using von Frey filaments on the dorsal and midplantar regions of the hindpaws.Dorsal von Frey filament tests were a more reliable method than plantar von Frey filament tests to assess mechanical nociceptive sensitivity following sciatic nerve transections.Baseline withdrawal thresholds of the sciatic-mediated lateral dorsal region differed significantly across strain but not sex.Withdrawal thresholds did not change significantly from baseline in chronic Unoperated and Sham-operated rats.Following sciatic transection,all rats exhibited severe hyposensitivity to stimuli at the lateral dorsal region of the hindpaw ipsilateral to the injury.However,PEG-fused rats exhibited significantly earlier return to baseline withdrawal thresholds than Negative Control rats.Furthermore,PEG-fused rats with significantly improved Sciatic Functional Index scores at or after 4 weeks postoperatively exhibited yet-earlier von Frey filament recove ry compared with those without Sciatic Functional Index recovery,suggesting a correlation between successful PEG-fusion and both motor-dominant and sensory-dominant behavioral recoveries.This correlation was independent of the sex or strain of the rat.Furthermore,our data showed that the acceleration of von Frey filament sensory recovery to baseline was solely due to the PEG-fused sciatic nerve and not saphenous nerve collateral outgrowths.No chronic hypersensitivity developed in any rat up to 12 weeks.All these data suggest that PEG-fusion repair of transection peripheral nerve injuries co uld have important clinical benefits.
文摘BACKGROUND Meniscal tears are one of the most common knee injuries.After the diagnosis of a meniscal tear has been made,there are several factors physicians use to guide clinical decision-making.The influence of time between injury and isolated meniscus repair on patient outcomes is not well described.Assessing this relationship is important as it may influence clinical decision-making and can add to the preoperative patient education process.We hypothesized that increasing the time from injury to meniscus surgery would worsen postoperative outcomes.AIM To investigate the current literature for data on the relationship between time between meniscus injury and repair on patient outcomes.METHODS PubMed,Academic Search Complete,MEDLINE,CINAHL,and SPORTDiscus were searched for studies published between January 1,1995 and July 13,2023 on isolated meniscus repair.Exclusion criteria included concomitant ligament surgery,incomplete outcomes or time to surgery data,and meniscectomies.Patient demographics,time to injury,and postoperative outcomes from each study were abstracted and analyzed.RESULTS Five studies met all inclusion and exclusion criteria.There were 204(121 male,83 female)patients included.Three of five(60%)studies determined that time between injury and surgery was not statistically significant for postoperative Lysholm scores(P=0.62),Tegner scores(P=0.46),failure rate(P=0.45,P=0.86),and International Knee Documentation Committee scores(P=0.65).Two of five(40%)studies found a statistically significant increase in Lysholm scores with shorter time to surgery(P=0.03)and a statistically significant association between progression of medial meniscus extrusion ratio(P=0.01)and increasing time to surgery.CONCLUSION Our results do not support the hypothesis that increased time from injury to isolated meniscus surgery worsens postoperative outcomes.Decision-making primarily based on injury interval is thus not recommended.
基金supported by Yunnan Province Innovation Team of Prevention and Treatment for Brain Disease with Acupuncture and Tuina,No.202405AS350007Youth Top Talent Project of 10-thousand Talent Plan in Yunnan Province,No.YNWR-QNBJ-2018-345+3 种基金the National Natural Science Foundation of China,No.81960731Joint Special Project of Traditional Chinese Medicine in Science and Technology Department of Yunnan Province,Nos.2019FF002[-008],202001AZ070001-002 and 202001AZ070001-030Yunnan Province University Innovation Team Projects No.2019YGC04Yunnan Province Project Education Fund,Nos.2024Y406,2024Y414(all to PZ)。
文摘The exchange of information and materials between organelles plays a crucial role in regulating cellular physiological functions and metabolic levels.Mitochondria-associated endoplasmic reticulum membranes serve as physical contact channels between the endoplasmic reticulum membrane and the mitochondrial outer membrane,formed by various proteins and protein complexes.This microstructural domain mediates several specialized functions,including calcium(Ca^(2+))signaling,autophagy,mitochondrial morphology,oxidative stress response,and apoptosis.Notably,the dysregulation of Ca^(2+)signaling mediated by mitochondria-associated endoplasmic reticulum membranes is a critical factor in the pathogenesis of neurological diseases.Certain proteins or protein complexes within these membranes directly or indirectly regulate the distance between the endoplasmic reticulum and mitochondria,as well as the transduction of Ca^(2+)signaling.Conversely,Ca^(2+)signaling mediated by mitochondria-associated endoplasmic reticulum membranes influences other mitochondria-associated endoplasmic reticulum membraneassociated functions.These functions can vary significantly across different neurological diseases—such as ischemic stroke,traumatic brain injury,Alzheimer's disease,Parkinson's disease,amyotrophic lateral sclerosis,and Huntington's disease—and their respective stages of progression.Targeted modulation of these disease-related pathways and functional proteins can enhance neurological function and promote the regeneration and repair of damaged neurons.Therefore,mitochondria-associated endoplasmic reticulum membranes-mediated Ca^(2+)signaling plays a pivotal role in the pathological progression of neurological diseases and represents a significant potential therapeutic target.This review focuses on the effects of protein complexes in mitochondria-associated endoplasmic reticulum membranes and the distinct roles of mitochondria-associated endoplasmic reticulum membranes-mediated Ca^(2+)signaling in neurological diseases,specifically highlighting the early protective effects and neuronal damage that can result from prolonged mitochondrial Ca^(2+)overload or deficiency.This article provides a comprehensive analysis of the various mechanisms of Ca^(2+)signaling mediated by mitochondria-associated endoplasmic reticulum membranes in neurological diseases,contributing to the exploration of potential therapeutic targets for promoting neuroprotection and nerve repair.
文摘The plasma membrane(PM)plays an essential role in maintaining cell homeostasis,therefore,timely and effective repair of damage caused by factors such as mechanical rupture,pore-forming toxins,or pore-forming proteins is crucial for cell survival.PM damage induces membrane rupture and stimulates an immune response.However,damage resulting from regulated cell death processes,including pyroptosis,ferroptosis,and necroptosis,cannot be repaired by simple sealing mechanisms and thus,requires specialized repair machinery.Recent research has identified a PM repair mechanism of regulated cell death-related injury,mediated by the endosomal sorting complexes required for transport(ESCRT)machinery.Here,we review recent progress in elucidating the ESCRT machinery-mediated repair mechanism of PM injury,with particular focus on processes related to regulated cell death.This overview,along with continued research in this field,may provide novel insights into therapeutic targets for diseases associated with dysregulation of regulated cell death pathways.
文摘BACKGROUND Rotator cuff tears are a chief cause of shoulder pain and disability,and surgical repair is often required when conservative management fails.As digital health technologies have expanded,especially since the coronavirus disease 2019 pandemic,digitally augmented rehabilitation programs emerged as a potential alternative to conventional physical therapy.AIM To determine if digitally assisted rehabilitation could be as practical,or even more effective,than the traditional methods most patients currently follow.METHODS Six electronic databases,including PubMed,Scopus,Cochrane Library,Google Scholar,EMBASE,and Web of Science,were searched to find articles that compare digital-based rehabilitation and conventional treatment.Outcomes of interest were Disabilities of the Arm,Shoulder and Hand(DASH)score and range of motion.The quality assessment of the included studies was performed using the risk-of-bias tool for randomized trials tool.RESULTS Three randomized controlled trial studies were enrolled in this study,including 195 cases.We did not find any significant differences between the two groups in terms of DASH score,flexion range of motion,and external rotation range of motion.There was a significant difference between the two groups for abduction range of motion.CONCLUSION Digital home-based rehab seems to be a strong alternative to traditional methods,offering similar results for people recovering from rotator cuff surgery.This approach might also make rehab more accessible and engaging for patients.That said,further research is needed to fully understand the potential of digital rehabilitation and ensure it works effectively for everyone.
文摘Objectives:To assess outcomes of rectourethral fistula repair utilizing a gracilis flap in a largely radiated cohort.Patients and Methods:We performed a retrospective review of all gracilis interposition flap reconstruction surgeries performed for RUF at a university hospital in South Carolina between January 2010 and June 2023.All repairs utilized a multidisciplinary approach with urology,colorectal,and plastic surgery teams.Postoperatively,patients were maximally drained with foley catheter and suprapubic tube(SPT).Initial voiding cystourethrogram(VCUG)was performed at 4 weeks post-repair.If there was a persistent leak,catheter drainage was maintained for 4 additional weeks and VCUG was repeated.Success was defined as absence of leak on VCUG within 3 months after surgery.Results:22 patients met inclusion criteria.68%of patients had history of external beam radiation therapy(EBRT),13.6%had brachytherapy,and 40.9%had cryotherapy.Initial post-operative VCUG was negative in 10 patients(45.5%).Of the 12 patients with a persistent fistula,5(42%)had no evidence of fistula on subsequent VCUG after 4 weeks.Overall,68%of patients were successfully treated with gracilis interposition flap.There was a significant difference of repair success based on EBRT status(p<0.05).Conclusions:We report a success rate of 68%for gracilis flap repair of RUF.Our cohort had a higher rate of prior radiation therapy compared to other studies.A clinically significant portion of patients with an initial positive VCUG will seal their fistula with prolonged catheter drainage.Gracilis interposition flap is a reasonable surgical treatment for RUF.
基金supported by grants from the China Postdoctoral Science Foundation(Nos.2022TQ0397,2022MD723744,2022M710564,2022M720603)Natural Science Foundation of China(Nos.82272553,82102571,81974346,8210257,82472404)+8 种基金Chongqing Municipal Medical Youth Talent Support Program,Chongqing,China(No.YXQN202408)Natural Science Foundation of Chongqing,China(Nos.CSTB2022NSCQ-MSX0089,CSTB2022NSCQ-MSX0104,CSTB2024NSCQMSX0532)Joint Medical Research Project of Health Commission&Science and Technology Bureau of Chongqing,China(No.2024QNXM032)Special Project for the Central Government to Guide the Development of Local Science and Technology in Sichuan Province(No.2023ZYD0071)National Natural Science Foundation of Sichuan(No.24NSFSC1274)Project of Innovative Science Research for Postgraduate of Chongqing Municipal Education Committee,Chongqing,China(Nos.CYS22389,CYB240224)National Natural Science Foundation of Sichuan(No.2024NSFSC0678)Research Project of the Affiliated Hospital of North Sichuan Medical College(Nos.2023ZD002,2023-2ZD001,2024JB001)Disciplines Construction Program of The Third Affiliated Hospital of Chongqing Medical University(Nos.KY23035,KY23041).
文摘Osteochondral defects pose an enormous challenge,and no satisfactory therapy is available to date due to the hierarchy of the native tissue consisting of articular cartilage and subchondral bone.Constructing a scaffold with biological function and biomimetic structure is the key to achieving a high-quality repair effect.Herein,a natural polymer-based bilayer scaffold with a porous architecture similar to that of osteochondral tissue is designed,involving the transforming growth factor-beta3-liposome-loaded upper layer for superficial cartilage regeneration and the nanohydroxyapatite-coated lower layer for subchondral bone rehabilitation.This research is conducted to evaluate the effects of nanoparticle-modified bilayer scaffold to mimic the hierarchical pro-chondrogenic and proosteogenic microenvironment for the recruited endogenous bone marrow mesenchymal stem cells.The fabricated composites were evaluated for mechanical,physicochemical,biological properties,in vitro and in vivo tissue regeneration potential.Overall,the current bilayer scaffold could regenerate a cartilage-bone integrated tissue with a seamless interfacial integration and exhibited superior tissue repair outcomes compared to other single layer scaffolds based on morphological,radiological and histological evaluation,verifying that this novel graft could be an effective approach to tissue-engineered analogs of cartilage-subchondral bone and offer new therapeutic opportunities for osteochondral defect-associated diseases.
文摘BACKGROUND Inguinal and umbilical hernias are common neonatal conditions.Open hernia repair is currently the primary surgical treatment,but postoperative recurrence remains a significant risk.AIM To identify the risk factors for recurrence following open neonatal hernia repair.METHODS We retrospectively reviewed the data of 56 neonates who underwent open hernia repair at Shijiazhuang Maternal and Child Health Hospital between March 2021 and December 2023.The patients were categorized into recurrence and non-recurrence groups based on their experience of postoperative recurrence.Uni-variate analysis was performed to examine various factors,and those with P<0.1 in univariate analysis were included in multivariate logistic regression.No-mogram models were constructed,and their performance was evaluated using receiver operating characteristic curves.RESULTS Of the 56 children,11(19.64%)experienced postoperative recurrence,whereas the remaining 45(80.36%)did not.Univariate analysis identified anemia(P=0.079),persistent postoperative pain(P=0.049),and low birth weight(P=0.017)as factors associated with recurrence.Multivariate logistic regression analysis re-vealed that anemia(P=0.029),persistent postoperative pain(P=0.008),and low birth weight(P=0.009)were independent risk factors for recurrence after open hernia repair in neonates.CONCLUSION The risk of recurrence after open hernia repair should be closely monitored in neonates with low birth weight,anemia,and persistent postoperative pain.
基金the Department of Zoology,Visva-Bharati for providing infrastructural supportSreejata Kamila is grateful to the Council of Scientific and Industrial Research(CSIR),India for Senior Research Fellowship(CSIR File No.09/202(0102)/2019-EMR-I)+2 种基金Koushik Kumar Dey acknowledges the Department of Biotechnology,New Delhi for research fellowship(No.BT/PR28560/AAQ/3/919/2018)Shehnaz Islam is thankful to Maulana Azad National Fellowship(UGC ref ID-201920–345938)India for her financial support.
文摘Arsenic(As)and chromium(Cr)are two harmful toxicants as well as carcinogens which can coexist in polluted surface water and groundwater.This coexistence leads to mixture effects in animals including fish.Both of these heavy metals are reported to manifest reactive oxygen species(ROS)mediated toxicity.Though individual neurotoxic effects have been reported,their mixture effects,its mechanism and cellular responses against oxidative stress and DNA damages remain unknown.The present study evaluated the individual and mixture effects of As and Cr at their environmentally relevant concentrations in zebrafish(Danio rerio)brain after 15,30 and 60 days of exposure.Nrf2,a transcription factor is involved in the expressional regulation of enzymes needed to maintain cellular redox homeostasis.This study reported the expressional pattern of Nrf2 and its associated xenobiotic metabolizing enzyme Nqo1 and other markers of oxidative stress such as ROS generation,reduced glutathione level,lipid peroxidation and catalase activity.Increased malondialdehyde(MDA)content,glutathione level,and catalase activity indicated oxidative stress in exposed groups.In addition,this study revealed expressional alterations of neurotoxicity marker(ache),DNA repair(ogg1,apex1,creb1,polb,mlh1,msh2 and msh6)and tumor suppressor(p53,brca2)genes.Results of ROS generation,MDA level,histopathological analysis,gene expression and immunofluorescence study confirmed that As and Cr did not show antagonistic effects in combination rather indicated additive effects which was dose-dependent but not always linear.
文摘BACKGROUND Transplantectomy has long been considered the preferred treatment for spontaneous renal graft rupture,prioritizing patient safety over kidney salvage.In the last decade,there has been an increasing number of reports showing that,in selected scenarios,conservative management through graft repair represents a feasible option,challenging traditional approaches.CASE SUMMARY We describe the case of a 37-year-old sensitized XY patient who experienced early spontaneous graft rupture after receiving his second deceased donor kidney transplant.Following temporary hemodynamic stabilization and abdominal contrast enhanced computed tomography scan assessment,the recipient was brought back to theatre for surgical exploration.Possible causes of irreversible graft damage were immediately ruled out.The fractured upper pole of the transplanted kidney was repaired using a fibrin sealant,external compression,and a tailored polyglactin 910 mesh wrapped around the graft.The post-operative course was uneventful.After 20 months of follow up,the patient is doing very well,with excellent renal function and complete reabsorption of the mesh,as demonstrated by serial ultrasound evaluations of the graft.CONCLUSION Amid organ shortages and sensitized patients,graft nephrectomy is reserved for severe injuries;repair using sealants and mesh is effective.
基金Supported by the General Program of the Hubei Provincial Natural Science Foundation of China Key Project,No.2021CFB520.
文摘BACKGROUND Long head of biceps tendon(LHBT)transposition is a novel technique based on the double-row suture bridge method,utilizing autologous reconstruction to treat massive rotator cuff tears.AIM To evaluate the mid-to-long-term clinical outcomes following the double-row repair method for massive rotator cuff tears.METHODS This retrospective analysis included data from 53 patients with massive rotator cuff tears treated at our hospital between 2020 and 2021.The patients were divided into the double-row repair group(conventional group)and the doublerow repair combined with the LHBT transposition group(transposition group).Postoperative pain was assessed using the visual analogue scale at one week,one year,and the final follow-up.Shoulder function was evaluated using the American Shoulder and Elbow Surgeons and Constant-Murley scores at one year and the final follow-up.Rotator cuff healing was assessed postoperatively for one year using the Sugaya classification,which categorizes tendon integrity based on magnetic resonance imaging findings.RESULTS No perioperative complications were observed in any of the patients at any time.There were no significant differences between the groups regarding operative time and intraoperative blood loss.The transposition group had significantly lower visual analogue scale scores than the conventional group at one week postoperatively;however,there were no significant differences between the groups at one year or the final follow-up.At one year postoperatively,the transposition group showed significantly higher American Shoulder and Elbow Surgeons and Constant-Murley scores than the conventional group;no significant differences were observed at the final followup.There were no significant differences in rotator cuff healing between the groups at one year postoperatively.CONCLUSION Compared to double-row repair alone,double-row repair combined with LHBT transposition for treating massive rotator cuff tears more effectively alleviates short-term postoperative pain and improves shoulder function within the first year.
文摘BACKGROUND Incisional hernia(IH)is a common complication following liver transplantation(LT),contributing to significant morbidity and impaired quality of life.The interplay of transplant-specific factors,patient comorbidities,surgical complexity,and immunosuppression presents considerable challenges in hernia repair,often accompanied by substantial risks.AIM To assess the incidence,risk factors,and outcomes of IH repair in LT recipients.METHODS A systematic literature search was conducted across MEDLINE,EMBASE,Scopus,CINAHL,the Cochrane Library,Google Scholar,and PubMed,yielding 493 results.In accordance with PRISMA guidelines,39 studies reporting on IH following LT were included in the final analysis.Studies involving paediatric populations,hernias unrelated to transplant incisions,living liver donors,non-LT,and multiorgan transplants were excluded.Meta-analysis was performed using Cochrane RevMan software.The study has been registered with PROSPERO(CRD420-24563398).RESULTS A review of 39 studies revealed incidence of post-LT IH ranging from 1.7%to upto 42.8%.Pooled analysis showed comparable demographics among groups and post-LT IH incidence was higher in older age recipients[mean difference(MD)=2.39,95%CI:1.15-3.63,P<0.001],male gender(relative risk=1.42,95%CI:1.18-1.72,P<0.001),high body mass index(BMI)(MD=1.06,95%CI:0.82-1.29,P<0.001),Mercedez-Benz incision type[odds ratio(OR)=0.45,95%CI:0.21,0.96,P=0.04],and need for re-laparotomy(OR=2.49,95%CI:1.05-5.93,P=0.04).No significant differences were found in recurrence rates or wound complications between open and laparoscopic IH repairs.CONCLUSION Older recipient age,male gender,high BMI,Mercedes-Benz incision,and re-laparotomy after LT are significant risk factors for IH.In contrast,model for end-stage liver disease score,pre-LT ascites,acute rejection,and mammalian target of rapamycin inhibitor therapy do not appear to influence IH development.While open repair remains the predominant approach post-LT,no significant differences in recurrence or wound complication rates have been observed between open and laparoscopic repairs.However,open repair is associated with a shorter operative time.
文摘The article explains the legal definition of the term‘repair’as used in cosmetic efficacy claims:it refers to the ability to help maintain the normal condition of the applied area.By analysing methods for modelling skin damage,the paper comprehensively summarises the evaluation system for the‘repair’efficacy of cosmetics,introducing existing assessment methods for repair efficacy across different application areas,including facial care products,body care products,foot care products,scalp care products,hair care products,and lip care products.This aims to promote the standardisation and innovative development of repair-type cosmetics.
基金support from the National Key Research and Development Program of China(No.2021YFB3802105-3)the National Natural Science Foundation of China(No.62173043).
文摘Exosomes derived from bone mesenchymal stem cells(BMSCs)show promising potential for treating bone defects.However,their clinical application is hindered by low yield and insufficient repair ability.Three-dimensional(3D)mechanical stimulation has been a well-known method for enhancing exosome secretion;however,the traditional stimulation process is always achieved by controlling the displacement of manipulators,which may induce uneven loading distribution and degradation of stimulation strength.Here,we propose a micro-stretching manipulator that automatically controls the stretching force applied to gelatin methacryloyl(GelMA)/hyaluronic acid methacryloyl(HAMA)hybrid hydrogel sheets containing BMSCs within an incubator.To ensure the structural stability of the sheets after long-term stretching,the mixing ratio between GelMA and HAMA was optimized according to the mechanical property response of the sheets to cyclical loading.Subsequently,force-controlled mechanical loading was applied to the BMSC-laden sheets to produce exosomes.Compared with displacement control,force-controlled loading provides a more stable force stimulation,thereby enhancing exosome secretion.Furthermore,continuously stimulated exosomes exhibited a stronger capacity for promoting osteogenic differentiation of BMSCs and facilitating the repair of bone defects in a rat model.These findings suggest that force-controlled loading of cell-laden hydrogels offers a novel approach for the production of BMSC-derived exosomes and their application in bone repair.
文摘BACKGROUND The presence of a large paraesophageal hernia is a source of concern in foregut surgery.Thus,scholars have focused on ascertaining the optimal surgical approach,methods for reinforcing the esophageal hiatus,and strategies for preventing hernia recurrence and gastroesophageal reflux.AIM To investigate the outcomes of surgery for giant paraesophageal hernias without sac removal.METHODS Sixty-six consecutive patients who underwent surgery for a giant paraesophageal hernia between May 2010 and December 2024 were included in this retrospective study.The pre-and postoperative examinations included upper gastrointestinal endoscopy,X-ray with barium contrast swallow,contrast-enhanced computed tomography(CT)scans of the chest and abdomen,24-hour potential hydrogen esophageal monitoring,and esophagomanometry.The study group included 36 patients who underwent surgery without sac removal,and the control group included 30 patients who underwent surgery with sac removal.RESULTS Fifty-two patients(28 in the study group and 24 in the control group)underwent laparoscopic procedures,10(6 in the study group and 4 in the control group)underwent open procedures,and 4(2 in each group)underwent conversion procedures.The operative time and postoperative length of stay were significantly longer in the control group than in the study group.In 12 patients in the study group,X-ray examination on postoperative days 3-5 revealed air-fluid levels at the site of the remaining hernia sac;all air-fluid levels disappeared without intervention 2 months later.Postoperative day 60 CT and X-ray examinations revealed no pathological changes related to the hernia sac in the mediastinum.CONCLUSION Removal of the hernia sac during surgery for giant paraesophageal hernias is not mandatory.Further large-scale multicentric randomized trials are needed for a more detailed investigation in this field.
基金supported by the National Key R&D Program of China(No.2023YFD1601400)the National Natural Science Foundation of China(Nos.82373912 and 82074068)+1 种基金Jiangsu Outstanding Youth Fund Project(No.BK20231535)the Fundamental Research Funds for the Central Universities(No.2632022YC04).
文摘The accumulation of deoxyribonucleic acid(DNA)oxidative damage mediated by reactive oxygen species(ROS)is closely associated with liver diseases.8-Oxoguanine(8-OxoG),a prevalent DNA oxidation product,plays a significant role in liver disease progression.The base excision repair(BER)pathway,comprising over 30 proteins including 8-OxoG DNA glycosylase1(OGG1),MutY homolog(MUTYH),and MutT homolog protein 1(MTH1),is responsible for the clearance and mismatch repair of 8-OxoG.Abnormally high levels of 8-OxoG and dysregulated expression and function of 8-OxoG repair enzymes contribute to the onset and development of liver diseases.Consequently,targeting the 8-OxoG production and repair system with agonists or inhibitors may offer a promising approach to liver disease treatment.This review summarizes the impact of 8-OxoG accumulation and dysregulated repair enzymes on various liver diseases,including viral liver disease,alcoholic liver disease(ALD),metabolic dysfunction-associated steatotic liver disease(MASLD),cholestatic liver disease(CLD),liver fibrosis,cirrhosis,and liver cancer.Additionally,we review natural constituents as potential therapeutic agents that regulate 8-OxoG production,repair enzymes,and repair system-related signal pathways in oxidative damage-induced liver diseases.
基金supported by the National Natural Science Foundation of China(grant no.82272287).
文摘Adipocyte-secreted extracellular vesicles(EVs)and adipose-derived stem cells(ADSCs)regulate physiological and pathological processes by delivering nucleic acids,proteins,and lipids.Both adipocyte-and ADSC-derived EVs regulate local inflammatory levels,tumor progression,and insulin sensitivity.These two types of EVs also have significant therapeutic effects on damage repair,including wound healing,angiogenesis,myocardial damage,vessel re-endothelialization,bone and cartilage regeneration,muscle repair,and nerve repair.With regard to wound healing,microRNA-21,microRNA-126,microRNA-31,and long non-coding RNA-H19 accelerate the proliferation and migration of fibroblasts,human immortalized keratinocytes,and endothelial cells via the PI3K/Akt/ERK pathway or fibrillin 1.ADSC-derived EVs contain various growth factors that are beneficial for wound healing.Numerous miRNAs in ADSC-derived EVs and β3-adrenergic receptors on brown adipocytes exhibit protective effects against myocardial infarction.Proteins in adipocyte-and ADSC-derived EVs play a role in promoting vessel re-endothelialization and regulating vasodilation.Angiogenesis is beneficial for the regeneration and repair of injured bone,cartilage,muscle,and nerves.Compared with adipocyte EVs,ADSC-EVs contain a greater variety of miRNAs and proteins that promote tissue regeneration.EV therapy is a promising cell-free therapy,and EV-loaded materials have been used for wound healing and myocardial damage.Future research will focus on identifying the molecules in EVs and the repair mechanisms that contribute to damage repair and regeneration.In addition,we aim to discover materials designed for slow release and specificity to facilitate tissue repair and optimize EV transportation.
