Background:The phenomenon of academic anxiety has been demonstrated to exert a considerable influence on students’academic engagement,leading to the emergence of a phenomenon known as“learned helplessness”and under...Background:The phenomenon of academic anxiety has been demonstrated to exert a considerable influence on students’academic engagement,leading to the emergence of a phenomenon known as“learned helplessness”and undermining the selfconfidence and motivation of high school students.Using acceptance-rejection theory,this study elucidated how a rejective parenting style affects Chinese high school students’academic anxiety and explored the urban-rural heterogeneity of this relationship.Methods:Data were analyzed using a stratified whole-cluster random sampling method.There are a total of 30,000 high school students in the three regions of northern and central China(from Shanxi,Hebei and Henan).A sample of 2286 high school students aged 14–19 years was ultimately selected from 2760 respondents for this investigation,which was conducted at the beginning of the 2023 school year.Pearson correlation,ordinary least squares(OLS)regression analysis,path analysis,and Fisher’s permutation test(FPT)were used to examine the effects of rejective parenting style on high school students’academic anxiety.Results:Results indicated a significant positive predictive effect between rejective parenting style and academic anxiety among high school students(β=0.815,t=116.211,p<0.001).Students’self-concept was significantly positively related to positive coping style(β=0.424,t=21.208,p<0.001)and chain-mediated this relationship.Therefore,this parenting style may indirectly mitigate academic anxiety through these mediators.The study also found that the effect of rejective parenting style on academic anxiety varied by students’residential background and was more pronounced in urban areas(0.226)than in rural areas(0.130).Conclusion:The research underscores the imperative for Chinese families to reexamine their utilization of rejection parenting and to prioritize the cultivation of students’intrinsic attributes.These findings offer a theoretical framework and practical evidence for policymakers and educators to develop efficacious and targeted interventions.In particular,greater attention should be directed towards the discrepancies in the manifestation of emotional and academic anxiety between urban and rural students,and prompt guidance should be furnished.展开更多
Background Hepatic alveolar echinococcosis （AE） is a parasitic disease in humans and caused by the Echinococcus multilocularis （Em）. Orthotopic liver transplantation （OLT） may be the only effective treatment for...Background Hepatic alveolar echinococcosis （AE） is a parasitic disease in humans and caused by the Echinococcus multilocularis （Em）. Orthotopic liver transplantation （OLT） may be the only effective treatment for end-stage hepatic AE. However, in some AE patients, extrahepatic Em can not be completely eliminated after OLT. We aimed to study whether the immunological changes caused by Em evasion may influence the rejective response. Methods Rat modles of AE were established by injecting the Em suspension into abdomen of Brown Norway （BN） rats. Three months later, in the experimental group, the liver was transplanted from Lewis （LEW） rats to Em-infected BN rats. In the control group, transplantation was from LEW rats to healthy BN rats. Liver tissue and peripheral blood （PB） samples were collected on days 1, 3, 5, and 7 after OLT. Liver tissue was analyzed after hematoxylin and eosin （H＆E） staining; numbers of CD4, CD8, and CD28 on peripheral blood cells were detected by flow cytometry; and expression of the chemokine fractalkine （Fkn） was detected by reverse transcription PCR （RT-PCR）. Interleukin-10 （IL-10） was measured in the serum by enzyme-linked immunosorbent assay （ELISA）. In every group, eight BN rats were retained for observing survival time. Results The survival times of recipients in the experimental group were prolonged compared with those in the control group. The rejective response occurred later and was milder in the experimental group, percentage of CD4, CD8, CD28 T-cells and Fkn mRNA expression were lower in the experimental group. While the serum IL-10 levels were higher in the experimental group than those in the control group. Conclusions Acute rejective response after OLT was attenuated in the rats with Em infection, and the recipients＂ survival time was prolonged. Em may play a role in this process by elevating IL-10 secretion, decreasing the effector T cells, inhibiting the expression of Fkn, which lead to reduce the inflammatory cells infiltration into the liver.展开更多
Antibody-mediated rejection(AMR)remains a leading cause of kidney allograft failure,posing significant clinical and economic challenges.Donor-specific antibodies against human leukocyte antigens or non-human leukocyte...Antibody-mediated rejection(AMR)remains a leading cause of kidney allograft failure,posing significant clinical and economic challenges.Donor-specific antibodies against human leukocyte antigens or non-human leukocyte antigens are critical risk factors for AMR and graft loss.The diagnostic criteria and classification of AMR have evolved considerably over the past three decades,driven largely by the Banff classification.The latest Banff 2022 classification introduced two additional subcategories of“microvascular inflammation,donor-specific antibody-negative,C4d-negative”and“probable AMR”.Traditionally,graft monitoring has relied on non-specific markers such as serum creatinine and proteinuria,and the invasive biopsies.Noninvasive tools using blood and urine biomarkers,including cellular assays and molecular profiling,are increasingly being investigated.Technologies such as the Molecular Microscope Diagnostic System show promise,with studies reporting 80%sensitivity and 90%specificity in detecting AMR.Treatment of AMR remains inconsistent.Recent advances,including CD38 antibodies,have demonstrated up to 60%efficacy in reversing AMR,while complement inhibition shows potential in severe early cases.Ongoing clinical trials evaluating high-dose intravenous immunoglobulin,efgartigimod,fostamatinib,and other novel therapies aim to expand treatment options.These developments highlight the need for well-designed clinical trials to validate biomarkers and therapies and to improve long-term outcomes for kidney transplant recipients.展开更多
Post-kidney transplant rejection is a critical factor influencing transplant success rates and the survival of transplanted organs.With the rapid advancement of artificial intelligence technologies,machine learning(ML...Post-kidney transplant rejection is a critical factor influencing transplant success rates and the survival of transplanted organs.With the rapid advancement of artificial intelligence technologies,machine learning(ML)has emerged as a powerful data analysis tool,widely applied in the prediction,diagnosis,and mechanistic study of kidney transplant rejection.This mini-review systematically summarizes the recent applications of ML techniques in post-kidney transplant rejection,covering areas such as the construction of predictive models,identification of biomarkers,analysis of pathological images,assessment of immune cell infiltration,and formulation of personalized treatment strategies.By integrating multi-omics data and clinical information,ML has significantly enhanced the accuracy of early rejection diagnosis and the capability for prognostic evaluation,driving the development of precision medicine in the field of kidney transplantation.Furthermore,this article discusses the challenges faced in existing research and potential future directions,providing a theoretical basis and technical references for related studies.展开更多
Nail changes following upper extremity transplantation(UET)cannot be overlooked as they possess diagnostic and prognostic relevance in allotransplantation of upper limbs.This comprehensive review explores nail and nai...Nail changes following upper extremity transplantation(UET)cannot be overlooked as they possess diagnostic and prognostic relevance in allotransplantation of upper limbs.This comprehensive review explores nail and nail bed related changes encountered in UET recipients in the literature.The differential diagnosis of nail abnormalities in UET includes a wide range of systemic,local and iatrogenic conditions other than immune responses to the allograft.It requires interdisciplinary evaluation by primary transplant surgeons,pathologists,dermatologists and immunologists.The possible underlying mechanisms of nail pathology in UET and the management are discussed.It also underscores the importance of onychodystrophy and need for timely intervention and to improve outcomes in UET recipients.展开更多
BACKGROUND Donor-specific antibodies(DSAs)against human leukocyte antigen(HLA)-DQ are increasingly recognized as major contributors to antibody-mediated rejection(AMR)and graft failure in kidney transplantation.Howeve...BACKGROUND Donor-specific antibodies(DSAs)against human leukocyte antigen(HLA)-DQ are increasingly recognized as major contributors to antibody-mediated rejection(AMR)and graft failure in kidney transplantation.However,their clinical impact remains understudied in Morocco.AIM To evaluate the presence and implications of anti-HLA-DQ DSAs in Moroccan kidney transplant recipients.METHODS We retrospectively analyzed the immunological profiles and clinical outcomes of kidney transplant recipients screened for anti-HLA antibodies between 2015 and 2020,who developed anti-HLA-DQ DSAs either before or after transplantation.Anti-HLA antibodies were identified using Luminex®single antigen bead technology,and clinical follow-up included graft function assessment,biopsy interpretation,and evaluation of immunosuppression.RESULTS In the pre-transplant group(n=6 with confirmed donor typing),patients with low to moderate median fluorescence intensity(MFI)anti-HLA-DQ DSAs(MFI 561-1581)underwent successful transplantation and maintained stable graft function under optimized immunosuppression.In contrast,in the post-transplant group(n=6 with confirmed donor typing),the emergence of de novo anti-HLA-DQ DSAs was consistently associated with AMR,with MFI values reaching up to 19473,with biopsy-proven AMR in 5 of 6 cases and suspicion of AMR in 1 case.Two representative cases are detailed to illustrate the clinical impact of DQ DSAs:one patient developed high-level anti-DQB1*02 de novo DSA(MFI 12029)with persistent AMR after 5 years,while another developed anti-DQA1*05:01 de novo DSA after an early AMR episode but maintained stable graft function after 5 years(creatinine 1.48 mg/dL).CONCLUSION Our findings underscore the clinical significance of anti-HLA-DQ DSAs in Moroccan kidney transplant recipients.While preformed DSAs with low immunogenicity may permit successful transplantation,de novo DSAs strongly correlate with AMR.Proactive monitoring,including routine DSA screening and HLA-DQ typing,could improve graft outcomes by enabling early intervention and better donor selection.展开更多
The role of antibodies in kidney transplant(KT)has evolved significantly over the past few decades.This role of antibodies in KT is multifaceted,encompassing both the challenges they pose in terms of antibody-mediated...The role of antibodies in kidney transplant(KT)has evolved significantly over the past few decades.This role of antibodies in KT is multifaceted,encompassing both the challenges they pose in terms of antibody-mediated rejection(AMR)and the opportunities for improving transplant outcomes through better detection,prevention,and treatment strategies.As our understanding of the immunological mechanisms continues to evolve,so too will the approaches to managing and harnessing the power of antibodies in KT,ultimately leading to improved patient and graft survival.This narrative review explores the multifaceted roles of antibodies in KT,including their involvement in rejection mechanisms,advancements in desensitization protocols,AMR treatments,and their potential role in monitoring and improving graft survival.展开更多
Over the past six decades,liver transplantation(LT)has evolved from an experimental procedure into a standardized and life-saving intervention,reshaping the landscape of organ transplantation.Driven by pioneering brea...Over the past six decades,liver transplantation(LT)has evolved from an experimental procedure into a standardized and life-saving intervention,reshaping the landscape of organ transplantation.Driven by pioneering breakthroughs,technological advancements,and a deepened understanding of immunology,LT has seen remarkable progress.Some of the most notable breakthroughs in the field include advances in immunosuppression,a revised model for end-stage liver disease,and artificial intelligence(AI)-integrated imaging modalities serving diagnostic and therapeutic roles in LT,paired with ever-evolving technological advances.Additionally,the refinement of transplantation procedures,resulting in the introduction of alternative transplantation methods,such as living donor LT,split LT,and the use of marginal grafts,has addressed the challenge of organ shortage.Moreover,precision medicine,guiding personalized immunosuppressive strategies,has significantly improved patient and graft survival rates while addressing emergent issues,such as short-term complications and early allograft dysfunction,leading to a more refined strategy and enhanced postoperative recovery.Looking ahead,ongoing research explores regenerative medicine,diagnostic tools,and AI to optimize organ allocation and posttransplantation car.In summary,the past six decades have marked a transformative journey in LT with a commitment to advancing science,medicine,and patient-centered care,offering hope and extending life to individuals worldwide.展开更多
The output feedback active disturbance rejection control of a valve-controlled cylinder electro-hydraulic servo system is investigated in this paper.First,a comprehensive nonlinear mathematical model that encompasses ...The output feedback active disturbance rejection control of a valve-controlled cylinder electro-hydraulic servo system is investigated in this paper.First,a comprehensive nonlinear mathematical model that encompasses both matched and mismatched disturbances is formulated.Due to the fact that only position information can be measured,a linear Extended State Observer(ESO)is introduced to estimate unknown states and matched disturbances,while a dedicated disturbance observer is constructed to estimate mismatched disturbances.Different from the traditional observer results,the design of the disturbance observer used in this study is carried out under the constraint of output feedback.Furthermore,an output feedback nonlinear controller is proposed leveraging the aforementioned observers to achieve accurate trajectory tracking.To mitigate the inherent differential explosion problem of the traditional backstepping framework,a finite-time stable command filter is incorporated.Simultaneously,considering transient filtering errors,a set of error compensation signals are designed to counter their negative impact effectively.Theoretical analysis affirms that the proposed control strategy ensures the boundedness of all signals within the closed-loop system.Additionally,under the specific condition of only time-invariant disturbances in the system,the conclusion of asymptotic stability is established.Finally,the algorithm’s efficacy is validated through comparative experiments.展开更多
Permanent magnet synchronous motor based electro-mechanical actuation servo drives have widespread applications in the aviation field,such as unmanned aerial vehicle electric servos,electric cabin doors,and mechanical...Permanent magnet synchronous motor based electro-mechanical actuation servo drives have widespread applications in the aviation field,such as unmanned aerial vehicle electric servos,electric cabin doors,and mechanical arms.The performance of the servo drive,which encompasses the response to the torque,efficiency,control bandwidth and the steady-state positioning accuracy,significantly influences the performance of the aviation actuation.Consequently,enhancing the control bandwidth and refining the positioning accuracy of aviation electro-mechanical actuation servo drives have emerged as a focal point of research.This paper investigates the multi-source disturbances present in aviation electro-mechanical actuation servo systems and summarizes recent research on high-performance servo control methods based on active disturbance rejection control(ADRC).We present a comprehensive overview of the research status pertaining to servo control architecture,strategies for suppressing disturbances in the current loop,and ADRC-based strategies for the position loop.We delineate the research challenges and difficulties encountered by aviation electro-mechanical actuation servo drive control technology.展开更多
Behavioral recovery using(viable)peripheral nerve allografts to repair ablation-type(segmental-loss)peripheral nerve injuries is delayed or poor due to slow and inaccurate axonal regeneration.Furthermore,such peripher...Behavioral recovery using(viable)peripheral nerve allografts to repair ablation-type(segmental-loss)peripheral nerve injuries is delayed or poor due to slow and inaccurate axonal regeneration.Furthermore,such peripheral nerve allografts undergo immunological rejection by the host immune system.In contrast,peripheral nerve injuries repaired by polyethylene glycol fusion of peripheral nerve allografts exhibit excellent behavioral recovery within weeks,reduced immune responses,and many axons do not undergo Wallerian degeneration.The relative contribution of neurorrhaphy and polyethylene glycol-fusion of axons versus the effects of polyethylene glycol per se was unknown prior to this study.We hypothesized that polyethylene glycol might have some immune-protective effects,but polyethylene glycol-fusion was necessary to prevent Wallerian degeneration and functional/behavioral recovery.We examined how polyethylene glycol solutions per se affect functional and behavioral recovery and peripheral nerve allograft morphological and immunological responses in the absence of polyethylene glycol-induced axonal fusion.Ablation-type sciatic nerve injuries in outbred Sprague–Dawley rats were repaired according to a modified protocol using the same solutions as polyethylene glycol-fused peripheral nerve allografts,but peripheral nerve allografts were loose-sutured(loose-sutured polyethylene glycol)with an intentional gap of 1–2 mm to prevent fusion by polyethylene glycol of peripheral nerve allograft axons with host axons.Similar to negative control peripheral nerve allografts not treated by polyethylene glycol and in contrast to polyethylene glycol-fused peripheral nerve allografts,animals with loose-sutured polyethylene glycol peripheral nerve allografts exhibited Wallerian degeneration for all axons and myelin degeneration by 7 days postoperatively and did not recover sciatic-mediated behavioral functions by 42 days postoperatively.Other morphological signs of rejection,such as collapsed Schwann cell basal lamina tubes,were absent in polyethylene glycol-fused peripheral nerve allografts but commonly observed in negative control and loose-sutured polyethylene glycol peripheral nerve allografts at 21 days postoperatively.Loose-sutured polyethylene glycol peripheral nerve allografts had more pro-inflammatory and less anti-inflammatory macrophages than negative control peripheral nerve allografts.While T cell counts were similarly high in loose-sutured-polyethylene glycol and negative control peripheral nerve allografts,loose-sutured polyethylene glycol peripheral nerve allografts expressed some cytokines/chemokines important for T cell activation at much lower levels at 14 days postoperatively.MHCI expression was elevated in loose-sutured polyethylene glycol peripheral nerve allografts,but MHCII expression was modestly lower compared to negative control at 21 days postoperatively.We conclude that,while polyethylene glycol per se reduces some immune responses of peripheral nerve allografts,successful polyethylene glycol-fusion repair of some axons is necessary to prevent Wallerian degeneration of those axons and immune rejection of peripheral nerve allografts,and produce recovery of sensory/motor functions and voluntary behaviors.Translation of polyethylene glycol-fusion technologies would produce a paradigm shift from the current clinical practice of waiting days to months to repair ablation peripheral nerve injuries.展开更多
In this article,we comment on an article published in a recent issue of the World Journal of Gastroenterology.We specifically focus on the roles of human leukocyte antigen(HLA)and donor-specific antibodies(DSAs)in ped...In this article,we comment on an article published in a recent issue of the World Journal of Gastroenterology.We specifically focus on the roles of human leukocyte antigen(HLA)and donor-specific antibodies(DSAs)in pediatric liver transpl-antation(LT),as well as the relationship between immune rejection after LT and DSA.Currently,LT remains the standard of care for pediatric patients with end-stage liver disease or severe acute liver failure.However,acute and chronic re-jection continues to be a significant cause of graft dysfunction and loss.HLA mismatch significantly reduces graft survival and increases the risk of acute rejection.Among them,D→R one-way mismatch at three loci was significantly related to graft-versus-host disease incidence after LT.The adverse impact of HLA-DSAs on LT recipients is already established.Therefore,the evaluation of HLA and DSA is crucial in pediatric LT.展开更多
In recent years, the use of new biomarkers in different phases of the diagnosis andtreatment of several diseases has allowed substantial improvement in clinicalpractice. The use of donor-derived cell-free DNA (dd-cfDN...In recent years, the use of new biomarkers in different phases of the diagnosis andtreatment of several diseases has allowed substantial improvement in clinicalpractice. The use of donor-derived cell-free DNA (dd-cfDNA) in organ transplantationhas led to significant progress in the treatment of post-transplantoutcomes, particularly after kidney transplantation. In addition, the use of ddcfDNAin organ transplantation has led to significant advancements in posttransplantoutcome monitoring. The aim of this study is to review many of therecent studies on the use of this biomarker and to evaluate its most relevantadvantages and limitations. dd-cfDNA is released from several types of cells ofthe transplanted organ, most often from endothelial cells and this happens in thecase of organ damage, most often rejection. Its presence in the bloodstream of therecipients is an important sign of graft damage;its principal advantage is in theavoidance of invasive tools such as renal biopsy. Additionally, several studiesreported that the finding of dd-cfDNA in the serum may precede histologicalabnormalities;its utility in the diagnosis of subclinical rejection is extremelyimportant. Among the principal limitations of this tool are the difficulty in distinguishingdifferent forms of graft damage. According to several studies this toolhas several limitations in diagnosing T-cell mediated rejection. In addition,particular care should be taken in distinguishing dd-cfDNA from recipientderivedcfDNA.展开更多
1 Active Disturbance Rejection Control(ADRC):a brief survey Since its inception,Active Disturbance Rejection Control(ADRC)has re-centered feedback controller design around two fundamental ideas—along with a consequen...1 Active Disturbance Rejection Control(ADRC):a brief survey Since its inception,Active Disturbance Rejection Control(ADRC)has re-centered feedback controller design around two fundamental ideas—along with a consequential design simplification:real-time estimation and online cancellation of the“total disturbance”conceived as the lumped effect of unknown internal dynamics and external inputs.The simplified design then proceeds in a customary fashion for the ideally remaining system model,which is devoid of the total disturbance.展开更多
Antibody-mediated rejection(AMR)represents a major challenge in kidney transplantation,significantly contributing to tissue injury and graft failure.AMR is primarily driven by donor-specific alloantibodies(DSAs),which...Antibody-mediated rejection(AMR)represents a major challenge in kidney transplantation,significantly contributing to tissue injury and graft failure.AMR is primarily driven by donor-specific alloantibodies(DSAs),which recognize and bind to specific target antigens present within the transplanted kidney tissue.Upon binding,these DSAs commonly initiate activation of the complement system within the graft.The activation of the complement cascade sets off a powerful inflammatory response characterized by the recruitment and activation of immune cells,endothelial damage,and subsequent tissue injury.This inflammation underlies many clinical and histological manifestations of AMR,making complement activation a critical player in the disease process.Advancements in our understanding of how complement pathways contribute to kidney graft injury have opened new avenues for therapeutic intervention.Recent research has facilitated the development and application of novel therapies specifically designed to inhibit complement activation.Such targeted complement-inhibitory strategies have shown promise in improving graft outcomes by inhibiting complement-mediated damage and extending graft survival.This review comprehensively discusses the critical role of complement activation in inducing kidney graft injury with a focus on its role in AMR.By elucidating the detailed mechanisms and contributions of complement pathways,the review seeks to enhance the understanding necessary for developing targeted therapeutic interventions to prevent or treat AMR effectively.展开更多
BACKGROUND The Luminex platform,where beads are coated with single human leukocyte antigens(HLA),detects HLA antibodies with higher sensitivity and specificity compared to complement-dependent cytotoxicity(CDC)assay a...BACKGROUND The Luminex platform,where beads are coated with single human leukocyte antigens(HLA),detects HLA antibodies with higher sensitivity and specificity compared to complement-dependent cytotoxicity(CDC)assay and flow crossmatch(FCXM).The clinical significance of donor-specific antibodies(DSAs)detected by this method is still under investigation.AIM To report the impact of low-level pretransplant DSAs detected by the Luminex platform on the rates of acute rejection(AR),allograft function,and long-term graft survival.METHODS This retrospective study was conducted at the Immunology Department of Sindh Institute of Urology and Transplantation,Karachi,Pakistan between January 2013 and December 2022.During this period 2714 patients were transplanted.Out of these patients 78(2.9%)patients had low-level DSAs detected by the Luminex flow beads method and were negative by CDC and FCXM with their donors.All recipients received ABO-compatible live-related kidney transplants.All patients had a minimum follow-up of 1 year.Graft rejection rates,graft function,and patient and graft survival were analyzed.The estimated glomerular filtration rate was calculated by the full CKD-EPI formula.RESULTS The mean age of all recipients was 29.57±10.11 years and 34.53±9.09 years for the donors.In 48(61.5%)patients,the cause of end-stage kidney disease was unknown.DSA against HLA class I was detected in 36(46.1%)patients,class II in 35(44.8%)patients,and both class I and II in 7(8.9%)patients.AR episodes were encountered in 8(10.3%)cases.Seven(87.5%)had T cell mediated rejection(type IA)and one acute antibody-mediated rejection.Antibody status was re-evaluated at the time of biopsy-proven ARs.Five(62.5%)patients lost their DSAs,while three(37.5%)had persistent DSAs.The mean estimated glomerular filtration rate at 1 year was 80.56±27.48 mL/min/1.73 m2 and at the last follow-up 73.41±28.80 mL/min/1.73 m2.The 1-year and 10-year patient and graft survival rates were 99%and 79%and 95%and 75%,respectively.During the follow-up period,10(12.8%)patients died,8 patients had a functioning graft,and 2 patients had failed grafts.Eight patients died due to cardiopulmonary arrest,and two died due to sepsis with failed grafts.CONCLUSION Patients with pretransplant low-level DSAs on Luminex without CDC and FCXM reactivity had good allograft outcomes at 1 year and 10 years as long as they are induced with biological agents and given potent maintenance immunosuppressants.展开更多
Antibody-mediated rejection(ABMR)and recurrent primary renal disease(PRD)represent major causes of kidney transplant(KT)loss.The standard of care for desensitization,ABMR,and relapsing autoimmune glomerulopathies or n...Antibody-mediated rejection(ABMR)and recurrent primary renal disease(PRD)represent major causes of kidney transplant(KT)loss.The standard of care for desensitization,ABMR,and relapsing autoimmune glomerulopathies or nephrotic syndrome includes apheresis for antibody removal and polyclonal immunoglobulin for antibody blockage.Although frequently used to achieve B-cell depletion,the administration of the type 1 anti-CD20 monoclonal antibodies(mAb)rituximab(RTX)or ofatumumab(OFA)has failed to demonstrate a significant survival benefit.Obinutuzumab(OBI)is a humanized glycoengineered type 2 anti-CD20 mAb.Compared to RTX or OFA,OBI-induced B-cell depletion is not related to complement-dependent cytotoxicity,mostly operating through antibody-dependent cell-mediated cytotoxicity,antibody-dependent phagocytosis,and direct cell death.These characteristics could play a pivotal role in the development of new anti-rejection strategies,enabling the simultaneous administration of complement inhibitors and B-cell-depleting agents.OBI has also demonstrated more powerful peripheral and central B-cell depletion capacities than RTX,with enhanced effects on memory B cells and plasmablasts.In patients with autoimmune glomerulopathies or multidrug-dependent nephrotic syndrome,OBI has shown encouraging results,representing a potential evolution of the treatment of post-transplant relapsing PRD.The present review summarizes the current knowledge on OBI use in KT setting.展开更多
Organ transplantation has long been recognized as an effective treatment for endstage organ failure,metabolic diseases,and malignant tumors.However,graft rejection caused by major histocompatibility complex mismatch r...Organ transplantation has long been recognized as an effective treatment for endstage organ failure,metabolic diseases,and malignant tumors.However,graft rejection caused by major histocompatibility complex mismatch remains a significant challenge.While modern immunosuppressants have made significant strides in reducing the incidence and risk of rejection,they have not been able to eliminate it completely.The intricate mechanisms underlying transplant rejection have been the subject of intense investigation by transplant immunologists.Among these factors,autophagy has emerged as a key player.Autophagy is an evolutionarily conserved mechanism in eukaryotic cells that mediates autophagocytosis and cellular protection.This process is regulated by autophagy-related genes and their encoded protein families,which maintain the material and energetic balance within cells.Additionally,autophagy has been reported to play crucial roles in the development,maturation,differentiation,and responses of immune cells.In the complex immune environment following transplantation,the role and mechanisms of autophagy are gradually being revealed.In this review,we aim to explore the current understanding of the role of autophagy in solid organ rejection after transplantation.Furthermore,we delve into the therapeutic advancements achieved by targeting autophagy involved in the rejection process.展开更多
Intestinal transplantation(ITx)has emerged as a pivotal life-saving intervention for patients with irreversible intestinal failure unresponsive to conventional medical and nutritional therapies.Despite its growing cli...Intestinal transplantation(ITx)has emerged as a pivotal life-saving intervention for patients with irreversible intestinal failure unresponsive to conventional medical and nutritional therapies.Despite its growing clinical acceptance,ITx remains among the most immunologically complex and technically demanding procedures in the field of solid organ transplantation.This review comprehensively summarizes the historical evolution,clinical indications,and advancements in surgical techniques,with emphasis on innovations in vascular anastomosis,multivisceral transplantation,and ex vivo preservation.Special attention is given to the unique immunological challenges of ITx,including bidirectional immune responses-host-vs-graft and graft-vs-host disease-immune-microbiota interactions,and the distinct roles of key immune cells.Pediatric and adult recipients exhibit divergent etiologies,immune responses,and complication profiles,necessitating individualized approaches.Although novel immunotherapeutic strategies and bioengineering innovations have improved short-term outcomes,chronic rejection,graft dysfunction,and immunosuppressive toxicity remain significant barriers.Looking ahead,future directions should prioritize precision immunomodulation,microbiome-targeted therapies,and integrated platforms for gene editing,3D bioprinting,and immune monitoring.Through multidisciplinary collaboration and translational research,ITx is poised to evolve from a high-risk salvage therapy into a personalized,sustainable solution that enhances long-term survival and patient quality of life.展开更多
The output regulation approach has effectively addressed the speed tracking and disturbance rejection problem of permanent magnet synchronous motor(PMSM).Although accurate speed tracking under time-varying load torque...The output regulation approach has effectively addressed the speed tracking and disturbance rejection problem of permanent magnet synchronous motor(PMSM).Although accurate speed tracking under time-varying load torque disturbance has been achieved,the number of disturbance frequencies should be known.In this paper,an adaptive observer-based error feedback control method is proposed,which can solve the speed tracking control problem of PMSM subject to completely unknown multi-frequency sinusoidal load torque disturbance,requiring only the upper bound of the number of disturbance frequencies.The design steps of this method can be divided into the following three steps.In step one,a filtered transformation is applied to convert the observer canonical form of the error system and the transformed exosystem into an adaptive observer form.In step two,an adaptive observer is designed to estimate the unknown parameters of the exosystem and states of the adaptive observer form.In step three,an adaptive observer-based error feedback controller is designed to solve this control problem.The effectiveness of the proposed method is demonstrated by experimental results.展开更多
基金funded by the Key Discipline Construction Project of the Liaoning Provincial Social Science Planning Fund(grant ID:L24ZD042)。
文摘Background:The phenomenon of academic anxiety has been demonstrated to exert a considerable influence on students’academic engagement,leading to the emergence of a phenomenon known as“learned helplessness”and undermining the selfconfidence and motivation of high school students.Using acceptance-rejection theory,this study elucidated how a rejective parenting style affects Chinese high school students’academic anxiety and explored the urban-rural heterogeneity of this relationship.Methods:Data were analyzed using a stratified whole-cluster random sampling method.There are a total of 30,000 high school students in the three regions of northern and central China(from Shanxi,Hebei and Henan).A sample of 2286 high school students aged 14–19 years was ultimately selected from 2760 respondents for this investigation,which was conducted at the beginning of the 2023 school year.Pearson correlation,ordinary least squares(OLS)regression analysis,path analysis,and Fisher’s permutation test(FPT)were used to examine the effects of rejective parenting style on high school students’academic anxiety.Results:Results indicated a significant positive predictive effect between rejective parenting style and academic anxiety among high school students(β=0.815,t=116.211,p<0.001).Students’self-concept was significantly positively related to positive coping style(β=0.424,t=21.208,p<0.001)and chain-mediated this relationship.Therefore,this parenting style may indirectly mitigate academic anxiety through these mediators.The study also found that the effect of rejective parenting style on academic anxiety varied by students’residential background and was more pronounced in urban areas(0.226)than in rural areas(0.130).Conclusion:The research underscores the imperative for Chinese families to reexamine their utilization of rejection parenting and to prioritize the cultivation of students’intrinsic attributes.These findings offer a theoretical framework and practical evidence for policymakers and educators to develop efficacious and targeted interventions.In particular,greater attention should be directed towards the discrepancies in the manifestation of emotional and academic anxiety between urban and rural students,and prompt guidance should be furnished.
基金This study was supported by grants from the National Natural Science Foundation of China （No. 30760239, No. 30960342） and High-tech Research and Development Projects of Xinjiang Uygur Autonomous Region （No. 200810104）. Conflicts of interest： None.
文摘Background Hepatic alveolar echinococcosis （AE） is a parasitic disease in humans and caused by the Echinococcus multilocularis （Em）. Orthotopic liver transplantation （OLT） may be the only effective treatment for end-stage hepatic AE. However, in some AE patients, extrahepatic Em can not be completely eliminated after OLT. We aimed to study whether the immunological changes caused by Em evasion may influence the rejective response. Methods Rat modles of AE were established by injecting the Em suspension into abdomen of Brown Norway （BN） rats. Three months later, in the experimental group, the liver was transplanted from Lewis （LEW） rats to Em-infected BN rats. In the control group, transplantation was from LEW rats to healthy BN rats. Liver tissue and peripheral blood （PB） samples were collected on days 1, 3, 5, and 7 after OLT. Liver tissue was analyzed after hematoxylin and eosin （H＆E） staining; numbers of CD4, CD8, and CD28 on peripheral blood cells were detected by flow cytometry; and expression of the chemokine fractalkine （Fkn） was detected by reverse transcription PCR （RT-PCR）. Interleukin-10 （IL-10） was measured in the serum by enzyme-linked immunosorbent assay （ELISA）. In every group, eight BN rats were retained for observing survival time. Results The survival times of recipients in the experimental group were prolonged compared with those in the control group. The rejective response occurred later and was milder in the experimental group, percentage of CD4, CD8, CD28 T-cells and Fkn mRNA expression were lower in the experimental group. While the serum IL-10 levels were higher in the experimental group than those in the control group. Conclusions Acute rejective response after OLT was attenuated in the rats with Em infection, and the recipients＂ survival time was prolonged. Em may play a role in this process by elevating IL-10 secretion, decreasing the effector T cells, inhibiting the expression of Fkn, which lead to reduce the inflammatory cells infiltration into the liver.
文摘Antibody-mediated rejection(AMR)remains a leading cause of kidney allograft failure,posing significant clinical and economic challenges.Donor-specific antibodies against human leukocyte antigens or non-human leukocyte antigens are critical risk factors for AMR and graft loss.The diagnostic criteria and classification of AMR have evolved considerably over the past three decades,driven largely by the Banff classification.The latest Banff 2022 classification introduced two additional subcategories of“microvascular inflammation,donor-specific antibody-negative,C4d-negative”and“probable AMR”.Traditionally,graft monitoring has relied on non-specific markers such as serum creatinine and proteinuria,and the invasive biopsies.Noninvasive tools using blood and urine biomarkers,including cellular assays and molecular profiling,are increasingly being investigated.Technologies such as the Molecular Microscope Diagnostic System show promise,with studies reporting 80%sensitivity and 90%specificity in detecting AMR.Treatment of AMR remains inconsistent.Recent advances,including CD38 antibodies,have demonstrated up to 60%efficacy in reversing AMR,while complement inhibition shows potential in severe early cases.Ongoing clinical trials evaluating high-dose intravenous immunoglobulin,efgartigimod,fostamatinib,and other novel therapies aim to expand treatment options.These developments highlight the need for well-designed clinical trials to validate biomarkers and therapies and to improve long-term outcomes for kidney transplant recipients.
文摘Post-kidney transplant rejection is a critical factor influencing transplant success rates and the survival of transplanted organs.With the rapid advancement of artificial intelligence technologies,machine learning(ML)has emerged as a powerful data analysis tool,widely applied in the prediction,diagnosis,and mechanistic study of kidney transplant rejection.This mini-review systematically summarizes the recent applications of ML techniques in post-kidney transplant rejection,covering areas such as the construction of predictive models,identification of biomarkers,analysis of pathological images,assessment of immune cell infiltration,and formulation of personalized treatment strategies.By integrating multi-omics data and clinical information,ML has significantly enhanced the accuracy of early rejection diagnosis and the capability for prognostic evaluation,driving the development of precision medicine in the field of kidney transplantation.Furthermore,this article discusses the challenges faced in existing research and potential future directions,providing a theoretical basis and technical references for related studies.
文摘Nail changes following upper extremity transplantation(UET)cannot be overlooked as they possess diagnostic and prognostic relevance in allotransplantation of upper limbs.This comprehensive review explores nail and nail bed related changes encountered in UET recipients in the literature.The differential diagnosis of nail abnormalities in UET includes a wide range of systemic,local and iatrogenic conditions other than immune responses to the allograft.It requires interdisciplinary evaluation by primary transplant surgeons,pathologists,dermatologists and immunologists.The possible underlying mechanisms of nail pathology in UET and the management are discussed.It also underscores the importance of onychodystrophy and need for timely intervention and to improve outcomes in UET recipients.
基金Supported by the National Science and Technology Research Center(Morocco)“PhD-Associate Scholarship-PASS”Program,No.88UH2C2023.
文摘BACKGROUND Donor-specific antibodies(DSAs)against human leukocyte antigen(HLA)-DQ are increasingly recognized as major contributors to antibody-mediated rejection(AMR)and graft failure in kidney transplantation.However,their clinical impact remains understudied in Morocco.AIM To evaluate the presence and implications of anti-HLA-DQ DSAs in Moroccan kidney transplant recipients.METHODS We retrospectively analyzed the immunological profiles and clinical outcomes of kidney transplant recipients screened for anti-HLA antibodies between 2015 and 2020,who developed anti-HLA-DQ DSAs either before or after transplantation.Anti-HLA antibodies were identified using Luminex®single antigen bead technology,and clinical follow-up included graft function assessment,biopsy interpretation,and evaluation of immunosuppression.RESULTS In the pre-transplant group(n=6 with confirmed donor typing),patients with low to moderate median fluorescence intensity(MFI)anti-HLA-DQ DSAs(MFI 561-1581)underwent successful transplantation and maintained stable graft function under optimized immunosuppression.In contrast,in the post-transplant group(n=6 with confirmed donor typing),the emergence of de novo anti-HLA-DQ DSAs was consistently associated with AMR,with MFI values reaching up to 19473,with biopsy-proven AMR in 5 of 6 cases and suspicion of AMR in 1 case.Two representative cases are detailed to illustrate the clinical impact of DQ DSAs:one patient developed high-level anti-DQB1*02 de novo DSA(MFI 12029)with persistent AMR after 5 years,while another developed anti-DQA1*05:01 de novo DSA after an early AMR episode but maintained stable graft function after 5 years(creatinine 1.48 mg/dL).CONCLUSION Our findings underscore the clinical significance of anti-HLA-DQ DSAs in Moroccan kidney transplant recipients.While preformed DSAs with low immunogenicity may permit successful transplantation,de novo DSAs strongly correlate with AMR.Proactive monitoring,including routine DSA screening and HLA-DQ typing,could improve graft outcomes by enabling early intervention and better donor selection.
文摘The role of antibodies in kidney transplant(KT)has evolved significantly over the past few decades.This role of antibodies in KT is multifaceted,encompassing both the challenges they pose in terms of antibody-mediated rejection(AMR)and the opportunities for improving transplant outcomes through better detection,prevention,and treatment strategies.As our understanding of the immunological mechanisms continues to evolve,so too will the approaches to managing and harnessing the power of antibodies in KT,ultimately leading to improved patient and graft survival.This narrative review explores the multifaceted roles of antibodies in KT,including their involvement in rejection mechanisms,advancements in desensitization protocols,AMR treatments,and their potential role in monitoring and improving graft survival.
文摘Over the past six decades,liver transplantation(LT)has evolved from an experimental procedure into a standardized and life-saving intervention,reshaping the landscape of organ transplantation.Driven by pioneering breakthroughs,technological advancements,and a deepened understanding of immunology,LT has seen remarkable progress.Some of the most notable breakthroughs in the field include advances in immunosuppression,a revised model for end-stage liver disease,and artificial intelligence(AI)-integrated imaging modalities serving diagnostic and therapeutic roles in LT,paired with ever-evolving technological advances.Additionally,the refinement of transplantation procedures,resulting in the introduction of alternative transplantation methods,such as living donor LT,split LT,and the use of marginal grafts,has addressed the challenge of organ shortage.Moreover,precision medicine,guiding personalized immunosuppressive strategies,has significantly improved patient and graft survival rates while addressing emergent issues,such as short-term complications and early allograft dysfunction,leading to a more refined strategy and enhanced postoperative recovery.Looking ahead,ongoing research explores regenerative medicine,diagnostic tools,and AI to optimize organ allocation and posttransplantation car.In summary,the past six decades have marked a transformative journey in LT with a commitment to advancing science,medicine,and patient-centered care,offering hope and extending life to individuals worldwide.
基金supported by the National Key R&D Program of China(No.2021YFB2011300)the Special Funds Project for the Transformation of Scientific and Technological Achievements of Jiangsu Province,China(No.BA2023039)+1 种基金the National Natural Science Foundation of China(No.52075262)the Fundamental Research Funds for the Central Universities,China(No.30922010706).
文摘The output feedback active disturbance rejection control of a valve-controlled cylinder electro-hydraulic servo system is investigated in this paper.First,a comprehensive nonlinear mathematical model that encompasses both matched and mismatched disturbances is formulated.Due to the fact that only position information can be measured,a linear Extended State Observer(ESO)is introduced to estimate unknown states and matched disturbances,while a dedicated disturbance observer is constructed to estimate mismatched disturbances.Different from the traditional observer results,the design of the disturbance observer used in this study is carried out under the constraint of output feedback.Furthermore,an output feedback nonlinear controller is proposed leveraging the aforementioned observers to achieve accurate trajectory tracking.To mitigate the inherent differential explosion problem of the traditional backstepping framework,a finite-time stable command filter is incorporated.Simultaneously,considering transient filtering errors,a set of error compensation signals are designed to counter their negative impact effectively.Theoretical analysis affirms that the proposed control strategy ensures the boundedness of all signals within the closed-loop system.Additionally,under the specific condition of only time-invariant disturbances in the system,the conclusion of asymptotic stability is established.Finally,the algorithm’s efficacy is validated through comparative experiments.
基金supported by the National Natural Science Foundation of China(Nos.52177059 and 52407064).
文摘Permanent magnet synchronous motor based electro-mechanical actuation servo drives have widespread applications in the aviation field,such as unmanned aerial vehicle electric servos,electric cabin doors,and mechanical arms.The performance of the servo drive,which encompasses the response to the torque,efficiency,control bandwidth and the steady-state positioning accuracy,significantly influences the performance of the aviation actuation.Consequently,enhancing the control bandwidth and refining the positioning accuracy of aviation electro-mechanical actuation servo drives have emerged as a focal point of research.This paper investigates the multi-source disturbances present in aviation electro-mechanical actuation servo systems and summarizes recent research on high-performance servo control methods based on active disturbance rejection control(ADRC).We present a comprehensive overview of the research status pertaining to servo control architecture,strategies for suppressing disturbances in the current loop,and ADRC-based strategies for the position loop.We delineate the research challenges and difficulties encountered by aviation electro-mechanical actuation servo drive control technology.
基金supported by grants from the Lone Star Paralysis Foundation,NIH R01NS081063Department of Defense award W81XWH-19-2-0054 to GDB+2 种基金supported by University of Wyoming Startup funds,Department of Defense grant W81XWH-17-1-0402the University of Wyoming Sensory Biology COBRE under National Institutes of Health(NIH)award number 5P20GM121310-02the National Institute of General Medical Sciences of the NIH under award number P20GM103432 to JSB。
文摘Behavioral recovery using(viable)peripheral nerve allografts to repair ablation-type(segmental-loss)peripheral nerve injuries is delayed or poor due to slow and inaccurate axonal regeneration.Furthermore,such peripheral nerve allografts undergo immunological rejection by the host immune system.In contrast,peripheral nerve injuries repaired by polyethylene glycol fusion of peripheral nerve allografts exhibit excellent behavioral recovery within weeks,reduced immune responses,and many axons do not undergo Wallerian degeneration.The relative contribution of neurorrhaphy and polyethylene glycol-fusion of axons versus the effects of polyethylene glycol per se was unknown prior to this study.We hypothesized that polyethylene glycol might have some immune-protective effects,but polyethylene glycol-fusion was necessary to prevent Wallerian degeneration and functional/behavioral recovery.We examined how polyethylene glycol solutions per se affect functional and behavioral recovery and peripheral nerve allograft morphological and immunological responses in the absence of polyethylene glycol-induced axonal fusion.Ablation-type sciatic nerve injuries in outbred Sprague–Dawley rats were repaired according to a modified protocol using the same solutions as polyethylene glycol-fused peripheral nerve allografts,but peripheral nerve allografts were loose-sutured(loose-sutured polyethylene glycol)with an intentional gap of 1–2 mm to prevent fusion by polyethylene glycol of peripheral nerve allograft axons with host axons.Similar to negative control peripheral nerve allografts not treated by polyethylene glycol and in contrast to polyethylene glycol-fused peripheral nerve allografts,animals with loose-sutured polyethylene glycol peripheral nerve allografts exhibited Wallerian degeneration for all axons and myelin degeneration by 7 days postoperatively and did not recover sciatic-mediated behavioral functions by 42 days postoperatively.Other morphological signs of rejection,such as collapsed Schwann cell basal lamina tubes,were absent in polyethylene glycol-fused peripheral nerve allografts but commonly observed in negative control and loose-sutured polyethylene glycol peripheral nerve allografts at 21 days postoperatively.Loose-sutured polyethylene glycol peripheral nerve allografts had more pro-inflammatory and less anti-inflammatory macrophages than negative control peripheral nerve allografts.While T cell counts were similarly high in loose-sutured-polyethylene glycol and negative control peripheral nerve allografts,loose-sutured polyethylene glycol peripheral nerve allografts expressed some cytokines/chemokines important for T cell activation at much lower levels at 14 days postoperatively.MHCI expression was elevated in loose-sutured polyethylene glycol peripheral nerve allografts,but MHCII expression was modestly lower compared to negative control at 21 days postoperatively.We conclude that,while polyethylene glycol per se reduces some immune responses of peripheral nerve allografts,successful polyethylene glycol-fusion repair of some axons is necessary to prevent Wallerian degeneration of those axons and immune rejection of peripheral nerve allografts,and produce recovery of sensory/motor functions and voluntary behaviors.Translation of polyethylene glycol-fusion technologies would produce a paradigm shift from the current clinical practice of waiting days to months to repair ablation peripheral nerve injuries.
文摘In this article,we comment on an article published in a recent issue of the World Journal of Gastroenterology.We specifically focus on the roles of human leukocyte antigen(HLA)and donor-specific antibodies(DSAs)in pediatric liver transpl-antation(LT),as well as the relationship between immune rejection after LT and DSA.Currently,LT remains the standard of care for pediatric patients with end-stage liver disease or severe acute liver failure.However,acute and chronic re-jection continues to be a significant cause of graft dysfunction and loss.HLA mismatch significantly reduces graft survival and increases the risk of acute rejection.Among them,D→R one-way mismatch at three loci was significantly related to graft-versus-host disease incidence after LT.The adverse impact of HLA-DSAs on LT recipients is already established.Therefore,the evaluation of HLA and DSA is crucial in pediatric LT.
文摘In recent years, the use of new biomarkers in different phases of the diagnosis andtreatment of several diseases has allowed substantial improvement in clinicalpractice. The use of donor-derived cell-free DNA (dd-cfDNA) in organ transplantationhas led to significant progress in the treatment of post-transplantoutcomes, particularly after kidney transplantation. In addition, the use of ddcfDNAin organ transplantation has led to significant advancements in posttransplantoutcome monitoring. The aim of this study is to review many of therecent studies on the use of this biomarker and to evaluate its most relevantadvantages and limitations. dd-cfDNA is released from several types of cells ofthe transplanted organ, most often from endothelial cells and this happens in thecase of organ damage, most often rejection. Its presence in the bloodstream of therecipients is an important sign of graft damage;its principal advantage is in theavoidance of invasive tools such as renal biopsy. Additionally, several studiesreported that the finding of dd-cfDNA in the serum may precede histologicalabnormalities;its utility in the diagnosis of subclinical rejection is extremelyimportant. Among the principal limitations of this tool are the difficulty in distinguishingdifferent forms of graft damage. According to several studies this toolhas several limitations in diagnosing T-cell mediated rejection. In addition,particular care should be taken in distinguishing dd-cfDNA from recipientderivedcfDNA.
文摘1 Active Disturbance Rejection Control(ADRC):a brief survey Since its inception,Active Disturbance Rejection Control(ADRC)has re-centered feedback controller design around two fundamental ideas—along with a consequential design simplification:real-time estimation and online cancellation of the“total disturbance”conceived as the lumped effect of unknown internal dynamics and external inputs.The simplified design then proceeds in a customary fashion for the ideally remaining system model,which is devoid of the total disturbance.
文摘Antibody-mediated rejection(AMR)represents a major challenge in kidney transplantation,significantly contributing to tissue injury and graft failure.AMR is primarily driven by donor-specific alloantibodies(DSAs),which recognize and bind to specific target antigens present within the transplanted kidney tissue.Upon binding,these DSAs commonly initiate activation of the complement system within the graft.The activation of the complement cascade sets off a powerful inflammatory response characterized by the recruitment and activation of immune cells,endothelial damage,and subsequent tissue injury.This inflammation underlies many clinical and histological manifestations of AMR,making complement activation a critical player in the disease process.Advancements in our understanding of how complement pathways contribute to kidney graft injury have opened new avenues for therapeutic intervention.Recent research has facilitated the development and application of novel therapies specifically designed to inhibit complement activation.Such targeted complement-inhibitory strategies have shown promise in improving graft outcomes by inhibiting complement-mediated damage and extending graft survival.This review comprehensively discusses the critical role of complement activation in inducing kidney graft injury with a focus on its role in AMR.By elucidating the detailed mechanisms and contributions of complement pathways,the review seeks to enhance the understanding necessary for developing targeted therapeutic interventions to prevent or treat AMR effectively.
文摘BACKGROUND The Luminex platform,where beads are coated with single human leukocyte antigens(HLA),detects HLA antibodies with higher sensitivity and specificity compared to complement-dependent cytotoxicity(CDC)assay and flow crossmatch(FCXM).The clinical significance of donor-specific antibodies(DSAs)detected by this method is still under investigation.AIM To report the impact of low-level pretransplant DSAs detected by the Luminex platform on the rates of acute rejection(AR),allograft function,and long-term graft survival.METHODS This retrospective study was conducted at the Immunology Department of Sindh Institute of Urology and Transplantation,Karachi,Pakistan between January 2013 and December 2022.During this period 2714 patients were transplanted.Out of these patients 78(2.9%)patients had low-level DSAs detected by the Luminex flow beads method and were negative by CDC and FCXM with their donors.All recipients received ABO-compatible live-related kidney transplants.All patients had a minimum follow-up of 1 year.Graft rejection rates,graft function,and patient and graft survival were analyzed.The estimated glomerular filtration rate was calculated by the full CKD-EPI formula.RESULTS The mean age of all recipients was 29.57±10.11 years and 34.53±9.09 years for the donors.In 48(61.5%)patients,the cause of end-stage kidney disease was unknown.DSA against HLA class I was detected in 36(46.1%)patients,class II in 35(44.8%)patients,and both class I and II in 7(8.9%)patients.AR episodes were encountered in 8(10.3%)cases.Seven(87.5%)had T cell mediated rejection(type IA)and one acute antibody-mediated rejection.Antibody status was re-evaluated at the time of biopsy-proven ARs.Five(62.5%)patients lost their DSAs,while three(37.5%)had persistent DSAs.The mean estimated glomerular filtration rate at 1 year was 80.56±27.48 mL/min/1.73 m2 and at the last follow-up 73.41±28.80 mL/min/1.73 m2.The 1-year and 10-year patient and graft survival rates were 99%and 79%and 95%and 75%,respectively.During the follow-up period,10(12.8%)patients died,8 patients had a functioning graft,and 2 patients had failed grafts.Eight patients died due to cardiopulmonary arrest,and two died due to sepsis with failed grafts.CONCLUSION Patients with pretransplant low-level DSAs on Luminex without CDC and FCXM reactivity had good allograft outcomes at 1 year and 10 years as long as they are induced with biological agents and given potent maintenance immunosuppressants.
文摘Antibody-mediated rejection(ABMR)and recurrent primary renal disease(PRD)represent major causes of kidney transplant(KT)loss.The standard of care for desensitization,ABMR,and relapsing autoimmune glomerulopathies or nephrotic syndrome includes apheresis for antibody removal and polyclonal immunoglobulin for antibody blockage.Although frequently used to achieve B-cell depletion,the administration of the type 1 anti-CD20 monoclonal antibodies(mAb)rituximab(RTX)or ofatumumab(OFA)has failed to demonstrate a significant survival benefit.Obinutuzumab(OBI)is a humanized glycoengineered type 2 anti-CD20 mAb.Compared to RTX or OFA,OBI-induced B-cell depletion is not related to complement-dependent cytotoxicity,mostly operating through antibody-dependent cell-mediated cytotoxicity,antibody-dependent phagocytosis,and direct cell death.These characteristics could play a pivotal role in the development of new anti-rejection strategies,enabling the simultaneous administration of complement inhibitors and B-cell-depleting agents.OBI has also demonstrated more powerful peripheral and central B-cell depletion capacities than RTX,with enhanced effects on memory B cells and plasmablasts.In patients with autoimmune glomerulopathies or multidrug-dependent nephrotic syndrome,OBI has shown encouraging results,representing a potential evolution of the treatment of post-transplant relapsing PRD.The present review summarizes the current knowledge on OBI use in KT setting.
基金Supported by the National Natural Science Foundation of China,No.82100691China Postdoctoral Science Foundation,No.2021M693631.
文摘Organ transplantation has long been recognized as an effective treatment for endstage organ failure,metabolic diseases,and malignant tumors.However,graft rejection caused by major histocompatibility complex mismatch remains a significant challenge.While modern immunosuppressants have made significant strides in reducing the incidence and risk of rejection,they have not been able to eliminate it completely.The intricate mechanisms underlying transplant rejection have been the subject of intense investigation by transplant immunologists.Among these factors,autophagy has emerged as a key player.Autophagy is an evolutionarily conserved mechanism in eukaryotic cells that mediates autophagocytosis and cellular protection.This process is regulated by autophagy-related genes and their encoded protein families,which maintain the material and energetic balance within cells.Additionally,autophagy has been reported to play crucial roles in the development,maturation,differentiation,and responses of immune cells.In the complex immune environment following transplantation,the role and mechanisms of autophagy are gradually being revealed.In this review,we aim to explore the current understanding of the role of autophagy in solid organ rejection after transplantation.Furthermore,we delve into the therapeutic advancements achieved by targeting autophagy involved in the rejection process.
基金Supported by Guangdong Provincial Medical Research Fund General Program,No.B2025209Guangzhou Science and Technology Program Project,No.2025A03J3269.
文摘Intestinal transplantation(ITx)has emerged as a pivotal life-saving intervention for patients with irreversible intestinal failure unresponsive to conventional medical and nutritional therapies.Despite its growing clinical acceptance,ITx remains among the most immunologically complex and technically demanding procedures in the field of solid organ transplantation.This review comprehensively summarizes the historical evolution,clinical indications,and advancements in surgical techniques,with emphasis on innovations in vascular anastomosis,multivisceral transplantation,and ex vivo preservation.Special attention is given to the unique immunological challenges of ITx,including bidirectional immune responses-host-vs-graft and graft-vs-host disease-immune-microbiota interactions,and the distinct roles of key immune cells.Pediatric and adult recipients exhibit divergent etiologies,immune responses,and complication profiles,necessitating individualized approaches.Although novel immunotherapeutic strategies and bioengineering innovations have improved short-term outcomes,chronic rejection,graft dysfunction,and immunosuppressive toxicity remain significant barriers.Looking ahead,future directions should prioritize precision immunomodulation,microbiome-targeted therapies,and integrated platforms for gene editing,3D bioprinting,and immune monitoring.Through multidisciplinary collaboration and translational research,ITx is poised to evolve from a high-risk salvage therapy into a personalized,sustainable solution that enhances long-term survival and patient quality of life.
基金supported by the National Natural Science Foundation of China(Nos.62273127 and 62073217)the Dreams Foundation of Jianghuai Advance Technology Center(No.2023-ZM01J006)the Anhui Provincial Key Research and Development Project(No.2022a05020025).
文摘The output regulation approach has effectively addressed the speed tracking and disturbance rejection problem of permanent magnet synchronous motor(PMSM).Although accurate speed tracking under time-varying load torque disturbance has been achieved,the number of disturbance frequencies should be known.In this paper,an adaptive observer-based error feedback control method is proposed,which can solve the speed tracking control problem of PMSM subject to completely unknown multi-frequency sinusoidal load torque disturbance,requiring only the upper bound of the number of disturbance frequencies.The design steps of this method can be divided into the following three steps.In step one,a filtered transformation is applied to convert the observer canonical form of the error system and the transformed exosystem into an adaptive observer form.In step two,an adaptive observer is designed to estimate the unknown parameters of the exosystem and states of the adaptive observer form.In step three,an adaptive observer-based error feedback controller is designed to solve this control problem.The effectiveness of the proposed method is demonstrated by experimental results.
