The interactions between avian brood parasites and their hosts provide an informative and easy-to-handle system for studying coevolution.Avian brood parasitism reduces the reproductive success of hosts,and thus,hosts ...The interactions between avian brood parasites and their hosts provide an informative and easy-to-handle system for studying coevolution.Avian brood parasitism reduces the reproductive success of hosts,and thus,hosts have evolved anti-parasitic strategies,such as rejecting parasitic eggs and adopting aggressive nest defense strategies,to avoid the cost brought on by brood parasitism.To test whether host anti-parasitic strategies are adjusted with the risk of being parasitized when the breeding seasons of brood parasites and hosts are not synchronous,we conducted a field experiment assessing nest defense and egg recognition behaviors of the Isabelline Shrike(Lanius isabellinus),a host of the Common Cuckoo(Cuculus canorus).In the local area,the host Isabelline Shrike begins to breed in April,whereas the summer migratory Common Cuckoo migrates to the local area in May and begins to lay parasitic eggs.Results showed that nest defense behaviors of the Isabelline Shrike increases significantly after cuckoo arrival,showing higher aggressiveness to cuckoo dummies,with no significant difference in attack rates among cuckoo,sparrowhawk and dove dummies,but their egg rejection did not change significantly.These results imply that Isabelline Shrikes may adjust their nest defense behavior,but not egg rejection behavior,with seasonality.展开更多
Permanent magnet synchronous motor(PMSM)speed control systems with conventional linear active disturbance rejection control(CLADRC)strategy encounter issues regarding the coupling between dynamic response and disturba...Permanent magnet synchronous motor(PMSM)speed control systems with conventional linear active disturbance rejection control(CLADRC)strategy encounter issues regarding the coupling between dynamic response and disturbance suppression and have poor performance in suppressing complex nonlinear disturbances.In order to address these issues,this paper proposes an improved two-degree-of-freedom LADRC(TDOF-LADRC)strategy,which can enhance the disturbance rejection performance of the system while decoupling entirely the system's dynamic and anti-disturbance performance to boost the system robustness and simplify controller parameter tuning.PMSM models that consider total disturbances are developed to design the TDOF-LADRC speed controller accurately.Moreover,to evaluate the control performance of the TDOF-LADRC strategy,its stability is proven,and the influence of each controller parameter on the system control performance is analyzed.Based on it,a comparison is made between the disturbance observation ability and anti-disturbance performance of TDOF-LADRC and CLADRC to prove the superiority of TDOF-LADRC in rejecting disturbances.Finally,experiments are performed on a 750 W PMSM experimental platform,and the results demonstrate that the proposed TDOF-LADRC exhibits the properties of two degrees of freedom and improves the disturbance rejection performance of the PMSM system.展开更多
Objective: To use bioinformatics technology to analyse differentially expressed genes in chronic rejection after renal transplantation, we can screen out potential pathogenic targets associated with the development of...Objective: To use bioinformatics technology to analyse differentially expressed genes in chronic rejection after renal transplantation, we can screen out potential pathogenic targets associated with the development of this disease, providing a theoretical basis for finding new therapeutic targets. Methods: Gene microarray data were downloaded from the Gene Expression Profiling Integrated Database (GEO) and cross-calculated to identify differentially expressed genes (DEGs). Analysis of differentially expressed genes (DEGs) with gene ontology (GO) is a method used to study the differences in gene expression under different conditions as well as their functions and interrelationships, while Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis is a tool used to explore the functions and pathways of genes in specific biological processes. By calculating the distribution of immune cell infiltration, the result of immune infiltration in the rejection group can be analysed as a trait in Weighted Gene Co-Expression Network Analysis (WGCNA) for genes associated with rejection. Then, protein-protein interaction networks (PPI) were constructed using the STRING database and Cytoscape software to identify hub gene markers. Results: A total of 60 integrated DEGs were obtained from 3 datasets (GSE7392, GSE181757, GSE222889). By GO and KEGG analysis, the GEDs were mainly concentrated in the regulation of immune response, defence response, regulation of immune system processes, and stimulation response. The pathways were mainly enriched in antigen processing and presentation, EBV infection, graft-versus-host, allograft rejection, and natural killer cell-mediated cytotoxicity. After further screening using WGCNA and PPI networks, HLA-A, HLA-B, HLA-F, and TYROBP were identified as hub genes (Hub genes). The data GSE21374 with clinical information was selected to construct the diagnostic efficacy and risk prediction model plots of the four hub genes, and the results concluded that all four Hub genes had good diagnostic value (area under the curve in the range of 0.794-0.819). From the inference, it can be concluded that the four genes, HLA-A, HLA-B, HLA-F and TYROBP, may have an important role in the development and progression of chronic rejection after renal transplantation. Conclusion: DEGs play an important role in the study of the pathogenesis of chronic rejection after renal transplantation, and can provide theoretical support for further research on the pathogenesis of chronic rejection after renal transplantation and the discovery of new therapeutic targets through enrichment analysis and pivotal gene screening, as well as inferential analyses of related diagnostic efficacy and disease risk prediction.展开更多
Anti-thymocyte globulin(ATG)is a pivotal immunosuppressive therapy utilized in the management of T-cell-mediated rejection and steroid-resistant rejection among renal transplant recipients.Commercially available as Th...Anti-thymocyte globulin(ATG)is a pivotal immunosuppressive therapy utilized in the management of T-cell-mediated rejection and steroid-resistant rejection among renal transplant recipients.Commercially available as Thymoglobulin(rabbit-derived,Sanofi,United States),ATG-Fresenius S(rabbit-derived),and ATGAM(equine-derived,Pfizer,United States),these formulations share a common mechanism of action centered on their interaction with cell surface markers of immune cells,imparting immunosuppressive effects.Although the prevailing mechanism predominantly involves T-cell depletion via the complement-mediated pathway,alternate mechanisms have been elucidated.Optimal dosing and treatment duration of ATG have exhibited variance across randomised trials and clinical reports,rendering the establishment of standardized guidelines a challenge.The spectrum of risks associated with ATG administration spans from transient adverse effects such as fever,chills,and skin rash in the acute phase to long-term concerns related to immunosuppression,including susceptibility to infections and malignancies.This comprehensive review aims to provide a thorough exploration of the current understanding of ATG,encompassing its mechanism of action,clinical utility in the treatment of acute renal graft rejections,specifically steroid-resistant cases,efficacy in rejection episode reversal,and a synthesis of findings from different eras of maintenance immunosuppression.Additionally,it delves into the adverse effects associated with ATG therapy and its impact on long-term graft function.Furthermore,the review underscores the existing gaps in evidence,particularly in the context of the Banff classification of rejections,and highlights the challenges faced by clinicians when navigating the available literature to strike the optimal balance between the risks and benefits of ATG utilization in renal transplantation.展开更多
Recognition and rejection of foreign eggs are effective defense of hosts against brood parasitism.However,brood parasitism can impose various selection pressures on different geographic populations of the same host sp...Recognition and rejection of foreign eggs are effective defense of hosts against brood parasitism.However,brood parasitism can impose various selection pressures on different geographic populations of the same host species.In a multiple cuckoo system in China,Azure-winged Magpies(Cyanopica cyanus)are parasitized by both Indian Cuckoos(Cuculus micropterus)and Asian Koels(Eudynamys scolopaceus).In this study,egg recognition ability and recognition mechanism of the Azure-winged Magpie were investigated using a population in Fusong,southeastern Jilin,China.The results showed that 55.6%(20/36)of the Azure-winged Magpies correctly rejected quail(Coturnix japonica)eggs in their nests,while 13.9%(5/36)of the individuals experienced rejection costs by wrongly rejecting their own eggs.Azure-winged Magpies could accurately reject the experimental eggs when the number of such eggs in the nests was the same as that of the magpie eggs.However,Azure-winged Magpies do not recognize and reject conspecific eggs(0/28).The present study indicates that the Azure-winged Magpie has moderate egg recognition ability toward non-mimetic quail eggs and shows a true recognition mechanism with rejecting foreign eggs by accurately recognizing their own eggs.However,they cannot recognize conspecific eggs.展开更多
BACKGROUND Capecitabine(CAP)is a classic antimetabolic drug and has shown potential antirejection effects after liver transplantation(LT)in clinical studies.Our previous study showed that metronomic CAP can cause the ...BACKGROUND Capecitabine(CAP)is a classic antimetabolic drug and has shown potential antirejection effects after liver transplantation(LT)in clinical studies.Our previous study showed that metronomic CAP can cause the programmed death of T cells by inducing oxidative stress in healthy mice.Ferroptosis,a newly defined non-apoptotic cell death that occurs in response to iron overload and lethal levels of lipid peroxidation,is an important mechanism by which CAP induces cell death.Therefore,ferroptosis may also play an important role in CAP-induced T cell death and play an immunosuppressive role in acute rejection after transplantation.AIM To investigate the functions and underlying mechanisms of antirejection effects of metronomic CAP.METHODS A rat LT model of acute rejection was established,and the effect of metronomic CAP on splenic hematopoietic function and acute graft rejection was evaluated 7 d after LT.In vitro,primary CD3+T cells were sorted from rat spleens and human peripheral blood,and co-cultured with or without 5-fluorouracil(5-FU)(active agent of CAP).The levels of ferroptosis-related proteins,ferrous ion concentration,and oxidative stress-related indicators were observed.The changes in mitochondrial structure were observed using electron microscopy.RESULTS With no significant myelotoxicity,metronomic CAP alleviated graft injury(Banff score 9 vs 7.333,P<0.001),prolonged the survival time of the recipient rats(11.5 d vs 16 d,P<0.01),and reduced the infiltration rate of CD3+T cells in peripheral blood(6.859 vs 3.735,P<0.001),liver graft(7.459 vs 3.432,P<0.001),and spleen(26.92 vs 12.9,P<0.001),thereby inhibiting acute rejection after LT.In vitro,5-FU,an end product of CAP metabolism,induced the degradation of the ferritin heavy chain by upregulating nuclear receptor coactivator 4,which caused the accumulation of ferrous ions.It also inhibited nuclear erythroid 2 p45-related factor 2,heme oxygenase-1,and glutathione peroxidase 4,eventually leading to oxidative damage and ferroptosis of T cells.CONCLUSION Metronomic CAP can suppress acute allograft rejection in rats by triggering CD3+T cell ferroptosis,which makes it an effective immunosuppressive agent after LT.展开更多
In this paper,a new distributed consensus tracking protocol incorporating local disturbance rejection is devised for a multi-agent system with heterogeneous dynamic uncertainties and disturbances over a directed graph...In this paper,a new distributed consensus tracking protocol incorporating local disturbance rejection is devised for a multi-agent system with heterogeneous dynamic uncertainties and disturbances over a directed graph.It is of two-degree-of-freedom nature.Specifically,a robust distributed controller is designed for consensus tracking,while a local disturbance estimator is designed for each agent without requiring the input channel information of disturbances.The condition for asymptotic disturbance rejection is derived.Moreover,even when the disturbance model is not exactly known,the developed method also provides good disturbance-rejection performance.Then,a robust stabilization condition with less conservativeness is derived for the whole multi-agent system.Further,a design algorithm is given.Finally,comparisons with the conventional one-degree-of-freedombased distributed disturbance-rejection method for mismatched disturbances and the distributed extended-state observer for matched disturbances validate the developed method.展开更多
BACKGROUND Gastroesophageal reflux is associated with poorer outcomes after lung transplant,likely through recurrent aspiration and allograft injury.Although prior studies have demonstrated a relationship between impe...BACKGROUND Gastroesophageal reflux is associated with poorer outcomes after lung transplant,likely through recurrent aspiration and allograft injury.Although prior studies have demonstrated a relationship between impedance-pH results and transplant outcomes,the role of esophageal manometry in the assessment of lung transplant patients remains debated,and the impact of esophageal dysmotility on transplant outcomes is unclear.Of particular interest is ineffective esophageal motility(IEM)and its associated impact on esophageal clearance.AIM To assess the relationship between pre-transplant IEM diagnosis and acute rejection after lung transplantation.METHODS This was a retrospective cohort study of lung transplant recipients at a tertiary care center between 2007 and 2018.Patients with pre-transplant anti-reflux surgery were excluded.Manometric and reflux diagnoses were recorded from pre-transplant esophageal function testing.Time-to-event analysis using Cox proportional hazards model was applied to evaluate outcome of first episode of acute cellular rejection,defined histologically per International Society of Heart and Lung Transplantation guidelines.Subjects not meeting this endpoint were censored at time of post-transplant anti-reflux surgery,last clinic visit,or death.Fisher’s exact test for binary variables and student’s t-test for continuous variables were performed to assess for differences between groups.RESULTS Of 184 subjects(54%men,mean age:58,follow-up:443 person-years)met criteria for inclusion.Interstitial pulmonary fibrosis represented the predominant pulmonary diagnosis(41%).During the follow-up period,60 subjects(33.5%)developed acute rejection.The all-cause mortality was 16.3%.Time-to-event univariate analyses demonstrated significant association between IEM and acute rejection[hazard ratio(HR):1.984,95%CI:1.03-3.30,P=0.04],confirmed on Kaplan-Meier curve.On multivariable analysis,IEM remained independently associated with acute rejection,even after controlling for potential confounders such as the presence of acid and nonacid reflux(HR:2.20,95%CI:1.18-4.11,P=0.01).Nonacid reflux was also independently associated with acute rejection on both univariate(HR:2.16,95%CI:1.26-3.72,P=0.005)and multivariable analyses(HR:2.10,95%CI:1.21-3.64,P=0.009),adjusting for the presence of IEM.CONCLUSION Pre-transplant IEM was associated with acute rejection after transplantation,even after controlling for acid and nonacid reflux.Esophageal motility testing may be considered in lung transplant to predict outcomes.展开更多
For the typical first-order systems with time-delay,this paper explors the control capability of linear active disturbance rejection control(LADRC).Firstly,the critical time-delay of LADRC is analyzed using the freque...For the typical first-order systems with time-delay,this paper explors the control capability of linear active disturbance rejection control(LADRC).Firstly,the critical time-delay of LADRC is analyzed using the frequency-sweeping method and the Routh criterion,and the stable time-delay interval starting from zero is accurately obtained,which reveals the limitations of general LADRC on large time-delay.Then in view of the large time-delay,an LADRC controller is developed and verified to be effective,along with the robustness analysis.Finally,numerical simulations show the accuracy of critical time-delay,and demonstrate the effectiveness and robustness of the proposed controller compared with other modified LADRCs.展开更多
Aiming at the problems of output voltage fluctuation and current total harmonic distortion(THD)in the front stage totem-pole bridgeless PFC of two-stage V2G(Vehicle to Grid)vehicle-mounted bi-directional converter,a f...Aiming at the problems of output voltage fluctuation and current total harmonic distortion(THD)in the front stage totem-pole bridgeless PFC of two-stage V2G(Vehicle to Grid)vehicle-mounted bi-directional converter,a fuzzy linear active disturbance rejection control strategy for V2G front-stage AC-DC power conversion system is proposed.Firstly,the topologicalworkingmode of the totem-pole bridgeless PFC is analyzed,and themathematical model is established.Combined with the system model and the linear active disturbance rejection theory,a double closed-loop controller is designed with the second-order linear active disturbance rejection control as the voltage outer loop and PI control as the current inner loop.The controller can realize self-adaptive tuning of the proportional gain coefficient of the active disturbance rejection controller through fuzzy reasoning and realize self-adaptive control.Simulation and experimental results show that this method can better solve the problems of slow system response and high total harmonic distortion rate of input current and effectively improve the system’s robustness.展开更多
Background: The allo-immune response following organ transplantation constitutes one of the main determinants concerning both short- and long- term outcomes in renal graft recipients. Chemokines and their receptors pl...Background: The allo-immune response following organ transplantation constitutes one of the main determinants concerning both short- and long- term outcomes in renal graft recipients. Chemokines and their receptors play a diversified and important role, either homeostatic or inflammatory and direct different immune-competent cell types to the allograft. While deeply studied in the last two decades, controversy persists as a result of chemokines’ pleiotropic actions. We report our analysis of CCR1, CCR3, CCR7, CCL5 and CX3CL1 expression or synthesis by graft-infiltrating cells in human kidney transplants (KTx). At the same time, we tested their robustness in diagnosing acute rejection. Methods: Fine-needle aspiration biopsies (Fnab) were performed either on days 7 or 14 post-transplantation among stable KTx and on the day of acute rejection (AR) diagnosis. Fnab cytopreparations were studied by the enzymatic avidin-biotin complex staining for CCR1, CCR3, CCR7 and CX3CL1. From another subgroup of cases, Fnab samples were cultured for 48 hours and the supernatants were analysed for CCL5 by ELISA. Results: The group of AR cases showed a significantly up-regulated expression of CCR1, CCR3, CCR7 and CX3CL1 and a significantly higher synthesis of CCL5. The positive predictive values were respectively 92%, 97%, 85%, 76% and 78% and negative predictive values were by the same order, 100%, 73%, 100%, 98% and 83%. Conclusions: Our study permits us to advance that CCR1 and CCR3 play a significant and non-redundant role in acute rejection, and it is the first report of CCR3 association with rejection, probably related to CCL5. The presence inside the graft of significant up-regulation for CCR7 surmises that part of antigen presentation may be performed there without being restricted to secondary lymphoid sites. Our results with CX3CL1 confirm other reports.展开更多
The rejected specimens from the Emergency Department of the Center of Clinical Laboratory from January 1,2022 to January 1,2023 were analyzed to reduce the specimen rejection rates and to improve the quality of inspec...The rejected specimens from the Emergency Department of the Center of Clinical Laboratory from January 1,2022 to January 1,2023 were analyzed to reduce the specimen rejection rates and to improve the quality of inspection.The results showed that there were 1488 samples of rejected specimens and the non-conforming rate was 0.58%.The departments involved were mainly the Emergency Department,the Hematology Department,the Cardiology Department,the Intensive Care Department,and the Brain Surgery Department.Among the reasons for rejection,blood hemolysis accounted for 43.15%,blood coagulation accounted for 26.61%,and the rate of insufficient specimens was 17.14%.Among them,the sample rejection rate for arterial blood gas analysis was the highest,which accounted for 1.74%;followed by specimens for coagulation test,which was 1.18%.These results indicate the main reason for producing rejected specimens is mainly due to not following the standard operating procedure.Specimen rejection can largely be avoided if the standards for specimen collection are strictly followed.展开更多
Chronic rejection(CR)of liver allografts causes damage to intrahepatic vessels and bile ducts and may lead to graft failure after liver transplantation.Although its prevalence has declined steadily with the introducti...Chronic rejection(CR)of liver allografts causes damage to intrahepatic vessels and bile ducts and may lead to graft failure after liver transplantation.Although its prevalence has declined steadily with the introduction of potent immunosuppressive therapy,CR still represents an important cause of graft injury,which might be irreversible,leading to graft loss requiring re-transplantation.To date,we still do not fully appreciate the mechanisms underlying this process.In addition to T cell-mediated CR,which was initially the only recognized type of CR,recently a new form of liver allograft CR,antibody-mediated CR,has been identified.This has indeed opened an era of thriving research and renewed interest in the field.Liver biopsy is needed for a definitive diagnosis of CR,but current research is aiming to identify new non-invasive tools for predicting patients at risk for CR after liver transplantation.Moreover,the minimization or withdrawal of immunosuppressive therapy might influence the establishment of subclinical CR-related injury,which should not be disregarded.Therapies for CR may only be effective in the“early”phases,and a tailored management of the immunosuppression regimen is essential for preventing irreversible liver damage.Herein,we provide an overview of the current knowledge and research on CR,focusing on early detection,identification of non-invasive biomarkers,immunosuppressive management,re-transplantation and future perspectives of CR.展开更多
BACKGROUND The liver has traditionally been regarded as resistant to antibody-mediated rejection(AMR).AMR in liver transplants is a field in its infancy compared to kidney and lung transplants.In our case we present a...BACKGROUND The liver has traditionally been regarded as resistant to antibody-mediated rejection(AMR).AMR in liver transplants is a field in its infancy compared to kidney and lung transplants.In our case we present a patient with alpha-1-antitrypsin disease who underwent ABO compatible liver transplant complicated by acute liver failure(ALF)with evidence of antibody mediated rejection on allograft biopsy and elevated serum donor-specific antibodies(DSA).This case highlights the need for further investigations and heightened awareness for timely diagnosis.CASE SUMMARY A 56 year-old woman with alpha-1-antitrypsin disease underwent ABO compatible liver transplant from a deceased donor.The recipient MELD at the time of transplant was 28.The flow cytometric crossmatches were noted to be positive for T and B lymphocytes.The patient had an uneventful recovery postoperatively.Starting on postoperative day 5 the patient developed fevers,elevated liver function tests,distributive shock,renal failure,and hepatic encephalopathy.She went into ALF with evidence of antibody mediated rejection with portal inflammation,bile duct injury,endothelitis,and extensive centrizonal necrosis,and C4d staining on allograft biopsy and elevated DSA.Despite various interventions including plasmapheresis and immunomodulating therapy,she continued to deteriorate.She was relisted and successfully underwent liver retransplantation.CONCLUSION This very rare case highlights AMR as the cause of ALF following liver transplant requiring retransplantation.展开更多
Primary sclerosing cholangitis (PSC) is a chronic progressive inflammatory disease affecting the bile ducts, leading to f ibrosis and eventually cirrhosis in most patients. Its etiology is unknown and so far no effect...Primary sclerosing cholangitis (PSC) is a chronic progressive inflammatory disease affecting the bile ducts, leading to f ibrosis and eventually cirrhosis in most patients. Its etiology is unknown and so far no effective medical therapy is available. Liver transplantation (LTX) is the only curative treatment and at present PSC is the main indication for LTX in the Scandinavian countries. Close to half of the PSC patients experience one or more episodes of acute cellular rejection (ACR) following transplantation and approximately 1/5 of the transplanted patients develop recurrent disease in the graft. In addition, some reports indicate that ACR early after LTX for PSC can infl uence the risk for recurrent disease. For these important post-transplantation entities affecting PSC patients, we have reviewed the current literature on epidemiology, pathogenesis, treatment and the possible infl uence of rejection on the risk of recurrent disease in the allograft.展开更多
AIM:To investigate the role of interleukin(IL)-17 in small bowel allograft rejection.METHODS:We detected the expression of helper T cell 17(Th17)cells in biopsy specimens from 3 cases of living small bowel transplanta...AIM:To investigate the role of interleukin(IL)-17 in small bowel allograft rejection.METHODS:We detected the expression of helper T cell 17(Th17)cells in biopsy specimens from 3 cases of living small bowel transplantation in our department through immunofluorescence stain.We then established a rat heterotopic small bowel transplantation model.The rats were sacrificed on the 1st,2nd,3rd,5th, and 7th d after small bowel transplantation.The degrees of transplantation rejection in rat intestine graft were examined through hematoxylin eosin(HE)stain, and the expression of Th17 cells in rat intestine graft were detected through immunofluorescence stain. In addition,the recipient rats undergoing intestinal transplantation were administrated with mouse-anti-rat IL-17 monoclonal antibody(mAb),and the survival of rats was analyzed.The recipient rats which received mouse-anti-rat IL-17 mAb treatment were sacrificed on the 1st,2nd,3rd,5th,and 7th d after small bowel transplantation.The degrees of transplantation rejection and the expression of Th17 cells in rat intestine graft were detected through HE and immunofluorescence stain. The expression of IL-17,IL-1β,tumor necroses factor receptor-α(TNF-α),IL-6,and IL-8 in the intestine graft or serum were also detected. RESULTS:The expressions of Th17 cells ran parallel with the degree of acute rejection in human intestine grafts.The intestine graft rejection of rats was aggravated with prolonged duration after intestinal transplantation,and the expressions of Th17 cells were also correlated with the degree of acute rejection in rat intestine grafts.Administration of mouse-anti-rat IL-17 mAb prolonged the survival of rats after small bowel transplantation(P<0.001).Furthermore,we found that the administration of mouse-anti-rat IL-17 mAb significantly decreased the intensity of CD4+IL-17+Th17 cells in intestine grafts on the 2nd,3rd,5th,and the 7th d (97.22±4.05vs 12.45±2.02 on the 7th d,P<0.0001), and suppressed the severity of acute rejection.The expression of IL-17 in the intestine graft declined after mouse-anti-rat IL-17 mAb administration on the 2nd,3rd,5th,and the 7th d(0.88±0.03 vs 0.35±0.02 on the 7th d,P<0.0001).We also detected the IL-17 serum level and found that the IL-17 level reduced from the 1st d to the 7th d(6.52±0.18 ng/mL vs 2.04±0.15 ng/mL on the 7th d,P<0.0001).No significant difference in the level of IL-17 mRNA in the intestine graft was identified between the two groups.The levels of IL-1β,TNF-α, IL-6,and IL-8 mRNA in the intestine graft after the administration of mouse-anti-rat IL-17 mAb were also tested.We found that on the 3rd,5th,and 7th d after intestinal transplantation,administration of mouse-anti- rat IL-17 mAb significantly inhibited the levels of IL-1β (12.11±1.16 vs 1.27±0.15 on the 7th d,P<0.001), TNF-α(27.37±2.60 vs 1.06±0.26 on the 7th d,P< 0.001),IL-6(21.43±1.79 vs 1.90±0.32 on the 7th d, P<0.001),and IL-8(20.44±1.44 vs 1.34±0.20 on the 7th d,P<0.001)mRNA in the intestine graft. CONCLUSION:IL-17 may act as a promising and potent target for inhibiting acute rejection after small bowel transplantation.展开更多
The evaluation of the immunosuppression state in liver transplanted patients is crucial for a correct posttransplant management and a major step towards the personalisation of the immunosuppressive therapy. However, c...The evaluation of the immunosuppression state in liver transplanted patients is crucial for a correct posttransplant management and a major step towards the personalisation of the immunosuppressive therapy. However, current immunological monitoring after liver transplantation relies mainly on clinical judgment and on immunosuppressive drug levels, without a proper assessment of the real suppression of theimmunological system. Various markers have been studied in an attempt to identify a specific indicator of graft rejection and graft acceptance after liver transplantation. Considering acute rejection, the most studied markers are pro-inflammatory and immunoregulatory cytokines and other proteins related to inflammation. However there is considerable overlap with other conditions, and only few of them have been validated. Standard liver tests cannot be used as markers of graft rejection due to their low sensitivity and specificity and the weak correlation with the severity of histopathological findings. Several studies have been performed to identify biomarkers of tolerance in liver transplanted patients. Most of them are based on the analysis of peripheral blood samples and on the use of transcriptional profiling techniques. Amongst these, NK cell-related molecules seem to be the most valid marker of graft acceptance, whereas the role CD4+CD25+Foxp3+ T cells has still to be properly defined.展开更多
Several previous studies have indicated that nest sanitation behavior is a general adaptation in altricial birds,with egg recog nition capacity evolvi ng as a specific response to in terspecific brood parasitism(IBP)....Several previous studies have indicated that nest sanitation behavior is a general adaptation in altricial birds,with egg recog nition capacity evolvi ng as a specific response to in terspecific brood parasitism(IBP).However,a rece nt study suggested an alternative hypothesis,con cludi ng that con specific brood parasitism(CBP)selects for egg rejection in thrushes,with IBP as a by-product.In the present study,we used a spectrophotometer to quantify egg coloration and egg mimicry and performed artificial parasitism experiments in the grey?backed thrush(Turdus hortulorum).We showed that individuals of this species rejected 100%of 12 foreign eggs,without IBP or CBP detected.In a review of previous studies,we also discuss possible explanations for the high egg rejection rate in the grey-backed thrush and suggest areas for future study.Altricial birds have evolved advaneed reproductive behavior to in crease the fitn ess of their offspring by buildi ng elaborate structures(i.e.,nests),in which they lay eggs and rear their nestlings(Hansell,2000).Bird nests not only provide a suitable place for nestling development,but also act as a concealed location for safety from predators.Furthermore,bird parents have evolved nest sanitation behavior to clean foreig n objects from their n ests,in eluding feces,eggshells,branches,and leaves,because they induce predation,facilitate microorganism growth,damage eggs,or hurt nestlings during brooding(Guigueno&Sealy,2012).Therefore,nest sanitation has evolved as a general behavior in altricial birds for distinguishing between egg-shaped and non-egg-shaped objects.展开更多
The hybrid vibration isolation, which takes advantages of both the passive and active approaches, has been an important solution for space missions. The objective of this paper is to design a vibration isolation platf...The hybrid vibration isolation, which takes advantages of both the passive and active approaches, has been an important solution for space missions. The objective of this paper is to design a vibration isolation platform for payloads on spacecrafts with the robust, wide bandwidth, and multi-degree-of-freedom(MDOF). The proposed solution is based on a parallel mechanism with six voice-coil motors(VCMs) as the actuators. The linear active disturbance resistance control(LADRC) algorithm is used for the active control. Numerical simulation results show that the vibration isolation platform performs effectively over a wide bandwidth, and the resonance introduced by the passive isolation is eliminated. The system robustness to the uncertainties of the structure is also verified by simulation.展开更多
基金funded by the National Natural Science Foundation of China (Nos. 31970427 and 32270526 to WL)。
文摘The interactions between avian brood parasites and their hosts provide an informative and easy-to-handle system for studying coevolution.Avian brood parasitism reduces the reproductive success of hosts,and thus,hosts have evolved anti-parasitic strategies,such as rejecting parasitic eggs and adopting aggressive nest defense strategies,to avoid the cost brought on by brood parasitism.To test whether host anti-parasitic strategies are adjusted with the risk of being parasitized when the breeding seasons of brood parasites and hosts are not synchronous,we conducted a field experiment assessing nest defense and egg recognition behaviors of the Isabelline Shrike(Lanius isabellinus),a host of the Common Cuckoo(Cuculus canorus).In the local area,the host Isabelline Shrike begins to breed in April,whereas the summer migratory Common Cuckoo migrates to the local area in May and begins to lay parasitic eggs.Results showed that nest defense behaviors of the Isabelline Shrike increases significantly after cuckoo arrival,showing higher aggressiveness to cuckoo dummies,with no significant difference in attack rates among cuckoo,sparrowhawk and dove dummies,but their egg rejection did not change significantly.These results imply that Isabelline Shrikes may adjust their nest defense behavior,but not egg rejection behavior,with seasonality.
文摘Permanent magnet synchronous motor(PMSM)speed control systems with conventional linear active disturbance rejection control(CLADRC)strategy encounter issues regarding the coupling between dynamic response and disturbance suppression and have poor performance in suppressing complex nonlinear disturbances.In order to address these issues,this paper proposes an improved two-degree-of-freedom LADRC(TDOF-LADRC)strategy,which can enhance the disturbance rejection performance of the system while decoupling entirely the system's dynamic and anti-disturbance performance to boost the system robustness and simplify controller parameter tuning.PMSM models that consider total disturbances are developed to design the TDOF-LADRC speed controller accurately.Moreover,to evaluate the control performance of the TDOF-LADRC strategy,its stability is proven,and the influence of each controller parameter on the system control performance is analyzed.Based on it,a comparison is made between the disturbance observation ability and anti-disturbance performance of TDOF-LADRC and CLADRC to prove the superiority of TDOF-LADRC in rejecting disturbances.Finally,experiments are performed on a 750 W PMSM experimental platform,and the results demonstrate that the proposed TDOF-LADRC exhibits the properties of two degrees of freedom and improves the disturbance rejection performance of the PMSM system.
基金National Natural Science Foundation of China(No.82260154)。
文摘Objective: To use bioinformatics technology to analyse differentially expressed genes in chronic rejection after renal transplantation, we can screen out potential pathogenic targets associated with the development of this disease, providing a theoretical basis for finding new therapeutic targets. Methods: Gene microarray data were downloaded from the Gene Expression Profiling Integrated Database (GEO) and cross-calculated to identify differentially expressed genes (DEGs). Analysis of differentially expressed genes (DEGs) with gene ontology (GO) is a method used to study the differences in gene expression under different conditions as well as their functions and interrelationships, while Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis is a tool used to explore the functions and pathways of genes in specific biological processes. By calculating the distribution of immune cell infiltration, the result of immune infiltration in the rejection group can be analysed as a trait in Weighted Gene Co-Expression Network Analysis (WGCNA) for genes associated with rejection. Then, protein-protein interaction networks (PPI) were constructed using the STRING database and Cytoscape software to identify hub gene markers. Results: A total of 60 integrated DEGs were obtained from 3 datasets (GSE7392, GSE181757, GSE222889). By GO and KEGG analysis, the GEDs were mainly concentrated in the regulation of immune response, defence response, regulation of immune system processes, and stimulation response. The pathways were mainly enriched in antigen processing and presentation, EBV infection, graft-versus-host, allograft rejection, and natural killer cell-mediated cytotoxicity. After further screening using WGCNA and PPI networks, HLA-A, HLA-B, HLA-F, and TYROBP were identified as hub genes (Hub genes). The data GSE21374 with clinical information was selected to construct the diagnostic efficacy and risk prediction model plots of the four hub genes, and the results concluded that all four Hub genes had good diagnostic value (area under the curve in the range of 0.794-0.819). From the inference, it can be concluded that the four genes, HLA-A, HLA-B, HLA-F and TYROBP, may have an important role in the development and progression of chronic rejection after renal transplantation. Conclusion: DEGs play an important role in the study of the pathogenesis of chronic rejection after renal transplantation, and can provide theoretical support for further research on the pathogenesis of chronic rejection after renal transplantation and the discovery of new therapeutic targets through enrichment analysis and pivotal gene screening, as well as inferential analyses of related diagnostic efficacy and disease risk prediction.
文摘Anti-thymocyte globulin(ATG)is a pivotal immunosuppressive therapy utilized in the management of T-cell-mediated rejection and steroid-resistant rejection among renal transplant recipients.Commercially available as Thymoglobulin(rabbit-derived,Sanofi,United States),ATG-Fresenius S(rabbit-derived),and ATGAM(equine-derived,Pfizer,United States),these formulations share a common mechanism of action centered on their interaction with cell surface markers of immune cells,imparting immunosuppressive effects.Although the prevailing mechanism predominantly involves T-cell depletion via the complement-mediated pathway,alternate mechanisms have been elucidated.Optimal dosing and treatment duration of ATG have exhibited variance across randomised trials and clinical reports,rendering the establishment of standardized guidelines a challenge.The spectrum of risks associated with ATG administration spans from transient adverse effects such as fever,chills,and skin rash in the acute phase to long-term concerns related to immunosuppression,including susceptibility to infections and malignancies.This comprehensive review aims to provide a thorough exploration of the current understanding of ATG,encompassing its mechanism of action,clinical utility in the treatment of acute renal graft rejections,specifically steroid-resistant cases,efficacy in rejection episode reversal,and a synthesis of findings from different eras of maintenance immunosuppression.Additionally,it delves into the adverse effects associated with ATG therapy and its impact on long-term graft function.Furthermore,the review underscores the existing gaps in evidence,particularly in the context of the Banff classification of rejections,and highlights the challenges faced by clinicians when navigating the available literature to strike the optimal balance between the risks and benefits of ATG utilization in renal transplantation.
基金funded by Key R&D projects in Ningxia (talent introduction project,2021BEB04015)Fundamental Research Funds for Central Universities,North Minzu University (2021KYQD05)+1 种基金supported by the National Natural Science Foundation of China (Nos.32160242 to JL,31960105 and 32260253 to LW,31970427 and32270526 to WL)supported by the specific research fund of The Innovation Platform for Academicians of Hainan Province
文摘Recognition and rejection of foreign eggs are effective defense of hosts against brood parasitism.However,brood parasitism can impose various selection pressures on different geographic populations of the same host species.In a multiple cuckoo system in China,Azure-winged Magpies(Cyanopica cyanus)are parasitized by both Indian Cuckoos(Cuculus micropterus)and Asian Koels(Eudynamys scolopaceus).In this study,egg recognition ability and recognition mechanism of the Azure-winged Magpie were investigated using a population in Fusong,southeastern Jilin,China.The results showed that 55.6%(20/36)of the Azure-winged Magpies correctly rejected quail(Coturnix japonica)eggs in their nests,while 13.9%(5/36)of the individuals experienced rejection costs by wrongly rejecting their own eggs.Azure-winged Magpies could accurately reject the experimental eggs when the number of such eggs in the nests was the same as that of the magpie eggs.However,Azure-winged Magpies do not recognize and reject conspecific eggs(0/28).The present study indicates that the Azure-winged Magpie has moderate egg recognition ability toward non-mimetic quail eggs and shows a true recognition mechanism with rejecting foreign eggs by accurately recognizing their own eggs.However,they cannot recognize conspecific eggs.
基金Supported by National Key Research and Development Program of China,No.2020YFA0710802The Youth Science Fund of the Nature Science Foundation of Tianjin,No.20JCQNJC01370+1 种基金The Key Projects of Tianjin Science and Technology Project,No.21JCZDJC00160The Science Foundation of Tianjin Health Commission,No.ZC20065 and No.ZC20089.
文摘BACKGROUND Capecitabine(CAP)is a classic antimetabolic drug and has shown potential antirejection effects after liver transplantation(LT)in clinical studies.Our previous study showed that metronomic CAP can cause the programmed death of T cells by inducing oxidative stress in healthy mice.Ferroptosis,a newly defined non-apoptotic cell death that occurs in response to iron overload and lethal levels of lipid peroxidation,is an important mechanism by which CAP induces cell death.Therefore,ferroptosis may also play an important role in CAP-induced T cell death and play an immunosuppressive role in acute rejection after transplantation.AIM To investigate the functions and underlying mechanisms of antirejection effects of metronomic CAP.METHODS A rat LT model of acute rejection was established,and the effect of metronomic CAP on splenic hematopoietic function and acute graft rejection was evaluated 7 d after LT.In vitro,primary CD3+T cells were sorted from rat spleens and human peripheral blood,and co-cultured with or without 5-fluorouracil(5-FU)(active agent of CAP).The levels of ferroptosis-related proteins,ferrous ion concentration,and oxidative stress-related indicators were observed.The changes in mitochondrial structure were observed using electron microscopy.RESULTS With no significant myelotoxicity,metronomic CAP alleviated graft injury(Banff score 9 vs 7.333,P<0.001),prolonged the survival time of the recipient rats(11.5 d vs 16 d,P<0.01),and reduced the infiltration rate of CD3+T cells in peripheral blood(6.859 vs 3.735,P<0.001),liver graft(7.459 vs 3.432,P<0.001),and spleen(26.92 vs 12.9,P<0.001),thereby inhibiting acute rejection after LT.In vitro,5-FU,an end product of CAP metabolism,induced the degradation of the ferritin heavy chain by upregulating nuclear receptor coactivator 4,which caused the accumulation of ferrous ions.It also inhibited nuclear erythroid 2 p45-related factor 2,heme oxygenase-1,and glutathione peroxidase 4,eventually leading to oxidative damage and ferroptosis of T cells.CONCLUSION Metronomic CAP can suppress acute allograft rejection in rats by triggering CD3+T cell ferroptosis,which makes it an effective immunosuppressive agent after LT.
基金supported by the National Natural Science Foundation of China(62003010,61873006,61673053)the Beijing Postdoctoral Research Foundation(Q6041001202001)+1 种基金the Postdoctoral Research Foundation of Chaoyang District(Q1041001202101)the National Key Research and Development Project(2018YFC1602704,2018YFB1702704)。
文摘In this paper,a new distributed consensus tracking protocol incorporating local disturbance rejection is devised for a multi-agent system with heterogeneous dynamic uncertainties and disturbances over a directed graph.It is of two-degree-of-freedom nature.Specifically,a robust distributed controller is designed for consensus tracking,while a local disturbance estimator is designed for each agent without requiring the input channel information of disturbances.The condition for asymptotic disturbance rejection is derived.Moreover,even when the disturbance model is not exactly known,the developed method also provides good disturbance-rejection performance.Then,a robust stabilization condition with less conservativeness is derived for the whole multi-agent system.Further,a design algorithm is given.Finally,comparisons with the conventional one-degree-of-freedombased distributed disturbance-rejection method for mismatched disturbances and the distributed extended-state observer for matched disturbances validate the developed method.
文摘BACKGROUND Gastroesophageal reflux is associated with poorer outcomes after lung transplant,likely through recurrent aspiration and allograft injury.Although prior studies have demonstrated a relationship between impedance-pH results and transplant outcomes,the role of esophageal manometry in the assessment of lung transplant patients remains debated,and the impact of esophageal dysmotility on transplant outcomes is unclear.Of particular interest is ineffective esophageal motility(IEM)and its associated impact on esophageal clearance.AIM To assess the relationship between pre-transplant IEM diagnosis and acute rejection after lung transplantation.METHODS This was a retrospective cohort study of lung transplant recipients at a tertiary care center between 2007 and 2018.Patients with pre-transplant anti-reflux surgery were excluded.Manometric and reflux diagnoses were recorded from pre-transplant esophageal function testing.Time-to-event analysis using Cox proportional hazards model was applied to evaluate outcome of first episode of acute cellular rejection,defined histologically per International Society of Heart and Lung Transplantation guidelines.Subjects not meeting this endpoint were censored at time of post-transplant anti-reflux surgery,last clinic visit,or death.Fisher’s exact test for binary variables and student’s t-test for continuous variables were performed to assess for differences between groups.RESULTS Of 184 subjects(54%men,mean age:58,follow-up:443 person-years)met criteria for inclusion.Interstitial pulmonary fibrosis represented the predominant pulmonary diagnosis(41%).During the follow-up period,60 subjects(33.5%)developed acute rejection.The all-cause mortality was 16.3%.Time-to-event univariate analyses demonstrated significant association between IEM and acute rejection[hazard ratio(HR):1.984,95%CI:1.03-3.30,P=0.04],confirmed on Kaplan-Meier curve.On multivariable analysis,IEM remained independently associated with acute rejection,even after controlling for potential confounders such as the presence of acid and nonacid reflux(HR:2.20,95%CI:1.18-4.11,P=0.01).Nonacid reflux was also independently associated with acute rejection on both univariate(HR:2.16,95%CI:1.26-3.72,P=0.005)and multivariable analyses(HR:2.10,95%CI:1.21-3.64,P=0.009),adjusting for the presence of IEM.CONCLUSION Pre-transplant IEM was associated with acute rejection after transplantation,even after controlling for acid and nonacid reflux.Esophageal motility testing may be considered in lung transplant to predict outcomes.
基金supported by the National Natural Science Foundation of China(61973175,61973172,62073177)the Key Technologies R&D Program of Tianjin(19JCZDJC32800)Tianjin Research Innovation Project for Postgraduate Students(2020YJSZXB02).
文摘For the typical first-order systems with time-delay,this paper explors the control capability of linear active disturbance rejection control(LADRC).Firstly,the critical time-delay of LADRC is analyzed using the frequency-sweeping method and the Routh criterion,and the stable time-delay interval starting from zero is accurately obtained,which reveals the limitations of general LADRC on large time-delay.Then in view of the large time-delay,an LADRC controller is developed and verified to be effective,along with the robustness analysis.Finally,numerical simulations show the accuracy of critical time-delay,and demonstrate the effectiveness and robustness of the proposed controller compared with other modified LADRCs.
基金supported by the Science and Technology Project of State Grid Corporation of China(W22KJ2722005)Tianyou Innovation Team of Lanzhou Jiaotong University(TY202009).
文摘Aiming at the problems of output voltage fluctuation and current total harmonic distortion(THD)in the front stage totem-pole bridgeless PFC of two-stage V2G(Vehicle to Grid)vehicle-mounted bi-directional converter,a fuzzy linear active disturbance rejection control strategy for V2G front-stage AC-DC power conversion system is proposed.Firstly,the topologicalworkingmode of the totem-pole bridgeless PFC is analyzed,and themathematical model is established.Combined with the system model and the linear active disturbance rejection theory,a double closed-loop controller is designed with the second-order linear active disturbance rejection control as the voltage outer loop and PI control as the current inner loop.The controller can realize self-adaptive tuning of the proportional gain coefficient of the active disturbance rejection controller through fuzzy reasoning and realize self-adaptive control.Simulation and experimental results show that this method can better solve the problems of slow system response and high total harmonic distortion rate of input current and effectively improve the system’s robustness.
文摘Background: The allo-immune response following organ transplantation constitutes one of the main determinants concerning both short- and long- term outcomes in renal graft recipients. Chemokines and their receptors play a diversified and important role, either homeostatic or inflammatory and direct different immune-competent cell types to the allograft. While deeply studied in the last two decades, controversy persists as a result of chemokines’ pleiotropic actions. We report our analysis of CCR1, CCR3, CCR7, CCL5 and CX3CL1 expression or synthesis by graft-infiltrating cells in human kidney transplants (KTx). At the same time, we tested their robustness in diagnosing acute rejection. Methods: Fine-needle aspiration biopsies (Fnab) were performed either on days 7 or 14 post-transplantation among stable KTx and on the day of acute rejection (AR) diagnosis. Fnab cytopreparations were studied by the enzymatic avidin-biotin complex staining for CCR1, CCR3, CCR7 and CX3CL1. From another subgroup of cases, Fnab samples were cultured for 48 hours and the supernatants were analysed for CCL5 by ELISA. Results: The group of AR cases showed a significantly up-regulated expression of CCR1, CCR3, CCR7 and CX3CL1 and a significantly higher synthesis of CCL5. The positive predictive values were respectively 92%, 97%, 85%, 76% and 78% and negative predictive values were by the same order, 100%, 73%, 100%, 98% and 83%. Conclusions: Our study permits us to advance that CCR1 and CCR3 play a significant and non-redundant role in acute rejection, and it is the first report of CCR3 association with rejection, probably related to CCL5. The presence inside the graft of significant up-regulation for CCR7 surmises that part of antigen presentation may be performed there without being restricted to secondary lymphoid sites. Our results with CX3CL1 confirm other reports.
文摘The rejected specimens from the Emergency Department of the Center of Clinical Laboratory from January 1,2022 to January 1,2023 were analyzed to reduce the specimen rejection rates and to improve the quality of inspection.The results showed that there were 1488 samples of rejected specimens and the non-conforming rate was 0.58%.The departments involved were mainly the Emergency Department,the Hematology Department,the Cardiology Department,the Intensive Care Department,and the Brain Surgery Department.Among the reasons for rejection,blood hemolysis accounted for 43.15%,blood coagulation accounted for 26.61%,and the rate of insufficient specimens was 17.14%.Among them,the sample rejection rate for arterial blood gas analysis was the highest,which accounted for 1.74%;followed by specimens for coagulation test,which was 1.18%.These results indicate the main reason for producing rejected specimens is mainly due to not following the standard operating procedure.Specimen rejection can largely be avoided if the standards for specimen collection are strictly followed.
文摘Chronic rejection(CR)of liver allografts causes damage to intrahepatic vessels and bile ducts and may lead to graft failure after liver transplantation.Although its prevalence has declined steadily with the introduction of potent immunosuppressive therapy,CR still represents an important cause of graft injury,which might be irreversible,leading to graft loss requiring re-transplantation.To date,we still do not fully appreciate the mechanisms underlying this process.In addition to T cell-mediated CR,which was initially the only recognized type of CR,recently a new form of liver allograft CR,antibody-mediated CR,has been identified.This has indeed opened an era of thriving research and renewed interest in the field.Liver biopsy is needed for a definitive diagnosis of CR,but current research is aiming to identify new non-invasive tools for predicting patients at risk for CR after liver transplantation.Moreover,the minimization or withdrawal of immunosuppressive therapy might influence the establishment of subclinical CR-related injury,which should not be disregarded.Therapies for CR may only be effective in the“early”phases,and a tailored management of the immunosuppression regimen is essential for preventing irreversible liver damage.Herein,we provide an overview of the current knowledge and research on CR,focusing on early detection,identification of non-invasive biomarkers,immunosuppressive management,re-transplantation and future perspectives of CR.
基金Corresponding author:Lena Sibulesky,MD,Associate Professor,Surgeon,Department of Surgery,University of Washington Medical Center,UWMC 1959 NE Pacific St,Box 356410 Seattle,Seattle,WA 98195,United States.lenasi@uw.edu。
文摘BACKGROUND The liver has traditionally been regarded as resistant to antibody-mediated rejection(AMR).AMR in liver transplants is a field in its infancy compared to kidney and lung transplants.In our case we present a patient with alpha-1-antitrypsin disease who underwent ABO compatible liver transplant complicated by acute liver failure(ALF)with evidence of antibody mediated rejection on allograft biopsy and elevated serum donor-specific antibodies(DSA).This case highlights the need for further investigations and heightened awareness for timely diagnosis.CASE SUMMARY A 56 year-old woman with alpha-1-antitrypsin disease underwent ABO compatible liver transplant from a deceased donor.The recipient MELD at the time of transplant was 28.The flow cytometric crossmatches were noted to be positive for T and B lymphocytes.The patient had an uneventful recovery postoperatively.Starting on postoperative day 5 the patient developed fevers,elevated liver function tests,distributive shock,renal failure,and hepatic encephalopathy.She went into ALF with evidence of antibody mediated rejection with portal inflammation,bile duct injury,endothelitis,and extensive centrizonal necrosis,and C4d staining on allograft biopsy and elevated DSA.Despite various interventions including plasmapheresis and immunomodulating therapy,she continued to deteriorate.She was relisted and successfully underwent liver retransplantation.CONCLUSION This very rare case highlights AMR as the cause of ALF following liver transplant requiring retransplantation.
文摘Primary sclerosing cholangitis (PSC) is a chronic progressive inflammatory disease affecting the bile ducts, leading to f ibrosis and eventually cirrhosis in most patients. Its etiology is unknown and so far no effective medical therapy is available. Liver transplantation (LTX) is the only curative treatment and at present PSC is the main indication for LTX in the Scandinavian countries. Close to half of the PSC patients experience one or more episodes of acute cellular rejection (ACR) following transplantation and approximately 1/5 of the transplanted patients develop recurrent disease in the graft. In addition, some reports indicate that ACR early after LTX for PSC can infl uence the risk for recurrent disease. For these important post-transplantation entities affecting PSC patients, we have reviewed the current literature on epidemiology, pathogenesis, treatment and the possible infl uence of rejection on the risk of recurrent disease in the allograft.
基金Supported by Grants from Scientific Technology Research Development Project of Shaanxi in part,No.2011K14-05-01,No.2008K12-01a Grant from the National Natural Scientific Foundation of China,No.31100643
文摘AIM:To investigate the role of interleukin(IL)-17 in small bowel allograft rejection.METHODS:We detected the expression of helper T cell 17(Th17)cells in biopsy specimens from 3 cases of living small bowel transplantation in our department through immunofluorescence stain.We then established a rat heterotopic small bowel transplantation model.The rats were sacrificed on the 1st,2nd,3rd,5th, and 7th d after small bowel transplantation.The degrees of transplantation rejection in rat intestine graft were examined through hematoxylin eosin(HE)stain, and the expression of Th17 cells in rat intestine graft were detected through immunofluorescence stain. In addition,the recipient rats undergoing intestinal transplantation were administrated with mouse-anti-rat IL-17 monoclonal antibody(mAb),and the survival of rats was analyzed.The recipient rats which received mouse-anti-rat IL-17 mAb treatment were sacrificed on the 1st,2nd,3rd,5th,and 7th d after small bowel transplantation.The degrees of transplantation rejection and the expression of Th17 cells in rat intestine graft were detected through HE and immunofluorescence stain. The expression of IL-17,IL-1β,tumor necroses factor receptor-α(TNF-α),IL-6,and IL-8 in the intestine graft or serum were also detected. RESULTS:The expressions of Th17 cells ran parallel with the degree of acute rejection in human intestine grafts.The intestine graft rejection of rats was aggravated with prolonged duration after intestinal transplantation,and the expressions of Th17 cells were also correlated with the degree of acute rejection in rat intestine grafts.Administration of mouse-anti-rat IL-17 mAb prolonged the survival of rats after small bowel transplantation(P<0.001).Furthermore,we found that the administration of mouse-anti-rat IL-17 mAb significantly decreased the intensity of CD4+IL-17+Th17 cells in intestine grafts on the 2nd,3rd,5th,and the 7th d (97.22±4.05vs 12.45±2.02 on the 7th d,P<0.0001), and suppressed the severity of acute rejection.The expression of IL-17 in the intestine graft declined after mouse-anti-rat IL-17 mAb administration on the 2nd,3rd,5th,and the 7th d(0.88±0.03 vs 0.35±0.02 on the 7th d,P<0.0001).We also detected the IL-17 serum level and found that the IL-17 level reduced from the 1st d to the 7th d(6.52±0.18 ng/mL vs 2.04±0.15 ng/mL on the 7th d,P<0.0001).No significant difference in the level of IL-17 mRNA in the intestine graft was identified between the two groups.The levels of IL-1β,TNF-α, IL-6,and IL-8 mRNA in the intestine graft after the administration of mouse-anti-rat IL-17 mAb were also tested.We found that on the 3rd,5th,and 7th d after intestinal transplantation,administration of mouse-anti- rat IL-17 mAb significantly inhibited the levels of IL-1β (12.11±1.16 vs 1.27±0.15 on the 7th d,P<0.001), TNF-α(27.37±2.60 vs 1.06±0.26 on the 7th d,P< 0.001),IL-6(21.43±1.79 vs 1.90±0.32 on the 7th d, P<0.001),and IL-8(20.44±1.44 vs 1.34±0.20 on the 7th d,P<0.001)mRNA in the intestine graft. CONCLUSION:IL-17 may act as a promising and potent target for inhibiting acute rejection after small bowel transplantation.
文摘The evaluation of the immunosuppression state in liver transplanted patients is crucial for a correct posttransplant management and a major step towards the personalisation of the immunosuppressive therapy. However, current immunological monitoring after liver transplantation relies mainly on clinical judgment and on immunosuppressive drug levels, without a proper assessment of the real suppression of theimmunological system. Various markers have been studied in an attempt to identify a specific indicator of graft rejection and graft acceptance after liver transplantation. Considering acute rejection, the most studied markers are pro-inflammatory and immunoregulatory cytokines and other proteins related to inflammation. However there is considerable overlap with other conditions, and only few of them have been validated. Standard liver tests cannot be used as markers of graft rejection due to their low sensitivity and specificity and the weak correlation with the severity of histopathological findings. Several studies have been performed to identify biomarkers of tolerance in liver transplanted patients. Most of them are based on the analysis of peripheral blood samples and on the use of transcriptional profiling techniques. Amongst these, NK cell-related molecules seem to be the most valid marker of graft acceptance, whereas the role CD4+CD25+Foxp3+ T cells has still to be properly defined.
基金supported by the National Natural Science Foundation of China(31672303 to C.Y.,31660617 to L.W.and 31472013 and 31772453 to W.L.)
文摘Several previous studies have indicated that nest sanitation behavior is a general adaptation in altricial birds,with egg recog nition capacity evolvi ng as a specific response to in terspecific brood parasitism(IBP).However,a rece nt study suggested an alternative hypothesis,con cludi ng that con specific brood parasitism(CBP)selects for egg rejection in thrushes,with IBP as a by-product.In the present study,we used a spectrophotometer to quantify egg coloration and egg mimicry and performed artificial parasitism experiments in the grey?backed thrush(Turdus hortulorum).We showed that individuals of this species rejected 100%of 12 foreign eggs,without IBP or CBP detected.In a review of previous studies,we also discuss possible explanations for the high egg rejection rate in the grey-backed thrush and suggest areas for future study.Altricial birds have evolved advaneed reproductive behavior to in crease the fitn ess of their offspring by buildi ng elaborate structures(i.e.,nests),in which they lay eggs and rear their nestlings(Hansell,2000).Bird nests not only provide a suitable place for nestling development,but also act as a concealed location for safety from predators.Furthermore,bird parents have evolved nest sanitation behavior to clean foreig n objects from their n ests,in eluding feces,eggshells,branches,and leaves,because they induce predation,facilitate microorganism growth,damage eggs,or hurt nestlings during brooding(Guigueno&Sealy,2012).Therefore,nest sanitation has evolved as a general behavior in altricial birds for distinguishing between egg-shaped and non-egg-shaped objects.
基金the National Natural Science Foundation of China (No. 11572215)the Fundamental Research Funds for the Central Universities (No. N160503002)the China Scholarship Council。
文摘The hybrid vibration isolation, which takes advantages of both the passive and active approaches, has been an important solution for space missions. The objective of this paper is to design a vibration isolation platform for payloads on spacecrafts with the robust, wide bandwidth, and multi-degree-of-freedom(MDOF). The proposed solution is based on a parallel mechanism with six voice-coil motors(VCMs) as the actuators. The linear active disturbance resistance control(LADRC) algorithm is used for the active control. Numerical simulation results show that the vibration isolation platform performs effectively over a wide bandwidth, and the resonance introduced by the passive isolation is eliminated. The system robustness to the uncertainties of the structure is also verified by simulation.
