BACKGROUND:Artificial materials composed of acellular heterogeneous nerves can resolve donor shortage problems for the repair of peripheral nerve defects.However,it remains unclear whether artificial materials can ove...BACKGROUND:Artificial materials composed of acellular heterogeneous nerves can resolve donor shortage problems for the repair of peripheral nerve defects.However,it remains unclear whether artificial materials can overcome immunological rejection of heterogeneous nerve grafts and obtain similar effects as allogeneic nerve grafts.OBJECTIVE:To analyze regeneration and immunological rejection of defective sciatic nerves in rats through the use of acellular heterogeneous nerve grafts.DESIGN,TIME AND SETTING:A randomized,controlled study was performed at the Department of Anatomy,China Medical University and the Experimental Center,First Affiliated Hospital,China Medical University between January and December 2008.MATERIALS:TritonX-100 (Sigma,USA) and deoxycholate (Pierce,USA) were used.METHODS:Bilateral sciatic nerves were collected from adult rabbits and treated with TritonX-100 and sodium deoxycholate to prepare acellular sciatic nerves,which were used to bridge 1-cm defective sciatic nerves in adult rats.MAIN OUTCOME MEASURES:The lymphocyte percentage in leukocytes was quantified following hemocyte staining.Neural regeneration and the recovery of motor end plates in the gastrocnemius muscle were observed under optical and electronic microscopy following toluidine blue staining,as well as acetylcholinesterase and succinate dehydrogenase histochemical staining.RESULTS:There was no significant difference in the lymphocyte percentage in leucocytes between transplanted and normal rats (P > 0.05).At 3 months after surgery,the rat toes on the operated side were separated and the rats could walk.In addition,the footplates exhibited an escape response when acupunctured.A large number of regenerated nerve fibers were observed in the transplant group,and acetylcholinesterase-positive motor end plates were visible in fibers of the gastrocnemius muscle.CONCLUSION:Acellular heterogeneous nerve transplants for the repair of defective sciatic nerves in rats promote neural regeneration without significant immunological rejection.展开更多
BACKGROUND: At present, it has been confirmed that immunological rejection exists in the cell transplantation in brain tissue, the effects of immunosuppressant on the immunological rejection and the survival of grafts...BACKGROUND: At present, it has been confirmed that immunological rejection exists in the cell transplantation in brain tissue, the effects of immunosuppressant on the immunological rejection and the survival of grafts in brain cell transplantation are worthy being investigated further. OBJECTIVE: To observe the immunological rejection after transgeneic cell transplantation in treating cerebral hemorrhage in rats, and investigate the interventional effect of cyclosprin. DESIGN: A randomized controlled study. SETTINGS: Second Affiliated Hospital of Xuzhou Medical College; First Affiliated Hospital of Nanjing Medical University. MATERIALS: Thirty-five healthy clean-degree SD rats of 6-8 weeks old were used, weighing 200-250 g, either male or female; The FACSort flow cytometer (American BD Company) and NYD-1000 image analytical system were used. The rat-anti-rat CD4 monoclonal antibody, rat-anti-rat CD8 monoclonal antibody, and rat-anti-rat MHC Ⅱ antigen monoclonal antibody were purchased from Santa Cruz Company; SP and DAB kits were purchased from Beijing Zhongshan Bio-engineering Company. XSP-8C2 light microscope was the product of Shanghai Zousun Optical Instrument, Co.,Ltd, and KYKY-3800B electron microscope was the product of China KYKY Technology Development Co.,Ltd. METHODS: The experiments were carried out in the animal experimental center of Nanjing Medical University from April to July in 2003. ① Model establishment: The rats were anesthetized, and then the coordinates of left internal capsule were identified, and the needle was withdrawn after 120 μL blood was injected into the internal capsule. Adenoviruses were taken as the carriers, after the astrocytes were successfully transfected by nerve growth factor(NGF) gene, 0.2 mL cell suspension was injected into the sites of cerebral hemorrhage. Thirty successfully established rat models were randomly divided into cyclosporin A group (n=18) and control group, the rats were treated with intraperitoneal injection of cyclosporin A (10 mg/kg per day) intraperitoneal injection of saline of the same dosage from the 1st day after transplantation, once a day for 7 days continuously. ② CD4+ and CD8+ detection: The CD4+ and CD8+ T lymphocytes in caudal vein were counted with flow cytometer at 15 days after treatment. ③ Morphological observation in the transplanted sites: The rats were killed and then brain tissues were taken out, the transplanted sites and the structure of the normal brain tissue around the transplanted sites were observed with light and electron microscopes. ④ Detections of the infiltration of T lymphocyte subsets and expression of major histocompatibility complex (MHC) Ⅱ antigen in the transplanted sites: The image analysis of immunohistochemical sections was performed with the image analytical system, and the integral optical density (IOD) was taken as the statistical value to observe the infiltration of T lymphocyte subsets and expression of MHCⅡ antigen in the transplanted sites, and the normal brain tissue around the transplanted sites were taken as controls. MAIN OUTCOME MEASURES: ① Countings of CD4+ and CD8+ in peripheral blood; ②Results of the morphological observation in the transplanted sites; ③ Infiltration of T lymphocyte subsets and expression of MHC Ⅱ antigen in the transplanted sites. RESULTS: Totally 35 rats were used, and 30 were successfully made into models, 5 died during the treatment, the other 25 were involved in the analysis of results. ① Results of CD4+ and CD8+ T lymphocytes in peripheral blood: The percentages of CD4+ and CD8+ T lymphocytes in the cyclosporin A group were (29.20±3.97)% and (20.65±2.02)%, respectively, which were obviously lower than those in the control group [(47.39±3.01)%, (28.30±2.36)%, t=4.983, 4.012, P < 0.05], and the CD4+/CD8+ ratio was obviously lower than that in the control group (1.41±0.86, 1.68±0.69, t=3. 871, P < 0.05). ② Morphological results in the transplanted sites: Under optical and electron microscopes, the survival region of the transplant was round, and it had an unobvious migration region with the normal brain tissues, the grafts had normal cellular form. Infiltrations of lymphocytes and monocytes were observed in both groups, and mainly located in the transplanted sites, and the expression of lymphocytes in the cyclosporin A group was markedly lower than that in the control group, and no above-mentioned changes were observed in the normal brain tissue around the transplanted sites. ③ Results of CD4+ and CD8+ T lymphocytes and expression of MHC Ⅱ antigen in the transplanted sites: The CD4+ and CD8+ T lymphocytes and expression of MHC Ⅱ antigen in the transplanted sites were observed in both groups. The IOD of CD4+ and CD8+ antigen positive cells in the cyclosporin A group were obviously lower than those in the control group (1.85±0.38, 1.44±0.33; 3.33±0.37, 2.64±0.56, t=4.122, 4.434, P < 0.05), and the IOD of MHC Ⅱ antigen positive cells was markedly lower than that in the control group (0.76±0.22, 0.98±0.24, t=3.885, P < 0.05). CONCLUSION: ① There is immunological rejection in brain tissue after the transplantation of NSC transgeneic glial cells. ② The immunosuppressant of cyclosporin A can reduce the immunological rejection after the cell transplantation.展开更多
Objective:To establish the polytransgenic mice expressing the human HT and complement regulatory proteins (CRPs) and discuss their ability to resist the hyperacute rejection (HAR) and delayed xenograft rejection (DXR)...Objective:To establish the polytransgenic mice expressing the human HT and complement regulatory proteins (CRPs) and discuss their ability to resist the hyperacute rejection (HAR) and delayed xenograft rejection (DXR) of heterogenic transplantation. Methods:Transgenic mice were produced by microinjection to construct gene for human HT, delay acceleration factor (DAF) and/or CD59 into the male pronucleus of zygote. PCR and Southern blot were used to screen the positive transgenic mice. Flow cytometry (FCM) was used to detect the expression of HT, α-Gal and DAF or CD59 on the PBMCs of transgenic mice. The survival time and function of the heart of transgenic mice were determined by a modified Langendorff cardiac perfusion apparatus. The change of proteinosis on IgM、IgG、C3c and C9 from different cardiac vascular endothelial cells of transgenic mice were detected by immunohistochemistry. Results:HT,DAF or CD59 were highly expressed on the positive transgenic mice by FCM. The deposition of IgM、IgG、C3c or C9 in the cardiac vascular endothelial cells of the positive transgenic mice were decreased. The survival time and function of the heart of the co-transgenic mice with AB serum perfusion were significantly longer and higher than that of the single HT positive transgenic mice(P<0.05). Conclusion:The mice co-expressing HT/DAF or HT/CD59 couldresist the HAR,which was better than those expressing HT alone. It is feasible to use HT and CRPs co-transgenic methods to resist the HAR and DXR.展开更多
Histamine in food has attracted widespread attention due to the potential toxicity and associated health risk.However,its influences on immunological components,especially the function of key immune cells,are still po...Histamine in food has attracted widespread attention due to the potential toxicity and associated health risk.However,its influences on immunological components,especially the function of key immune cells,are still poorly known.In this work,we explored the effects of exogenous histamine on the function of key immune cells such as intestinal epithelial cells,dendritic cells,and T cells.The results showed that histamine could affect the expression of allergy-related genes in CMT93 cells at a high dose of histamine.Moreover,it’s found that histamine could cause an imbalance in the levels of relevant immune factors secreted by dendritic cells and T cells,especially those related to allergy.At the same time,the proportion of MHC class IIpositive dendritic cells and the proportion of T helper 2(Th2)cells in CD4^(+)T cells increased after histamine stimulation.We concluded that the presence of a certain level of histamine in food may affect the expression of allergy-related cytokines,disrupt the balance of the immune homeostasis,and potentially lead to adverse immune reactions.This work demonstrated the importance of including the estimation of histamine’s immune safety in aquatic products rather than merely considering the potential risk of food poisoning.展开更多
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
Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and manageme...Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and management.It delves into host immune responses and reactivation’s delicate balance,spanning innate and adaptive immunity.Viral factors’disruption of this balance,as are interac-tions between viral antigens,immune cells,cytokine networks,and immune checkpoint pathways,are examined.Notably,the roles of T cells,natural killer cells,and antigen-presenting cells are discussed,highlighting their influence on disease progression.HBV reactivation’s impact on disease severity,hepatic flares,liver fibrosis progression,and hepatocellular carcinoma is detailed.Management strategies,including anti-viral and immunomodulatory approaches,are critically analyzed.The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation.In conclusion,this compre-hensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation.With a dedicated focus on understanding its implic-ations for disease progression and the prospects of efficient management stra-tegies,this article contributes significantly to the knowledge base.The more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches,ultimately enhancing disease management and elevating patient outcomes.The dynamic landscape of management strategies is critically scrutinized,spanning anti-viral and immunomodulatory approaches.The role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.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
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
AIM To evaluate the role of a therapeutic regimen with plasma exchange, intravenous immunoglobulins and rituximab in chronic-active antibody-mediated rejection(c AMR) settings.METHODS We compared 21 kidney transplant ...AIM To evaluate the role of a therapeutic regimen with plasma exchange, intravenous immunoglobulins and rituximab in chronic-active antibody-mediated rejection(c AMR) settings.METHODS We compared 21 kidney transplant recipients(KTRs) with a diagnosis of c AMR in a retrospective casecontrol analysis: nine KTRs treated with plasmapheresis, intravenous immunoglobulins and rituximab(PE-IVIGRTX group) vs 12 patients(control group) not treated with antibody-targeted therapies. We examined kidney survival and functional outcomes 24 mo after diagnosis. Histological features and donor-specific antibody(DSA) characteristics(MFI and C1 q-fixing ability) were also investigated.RESULTS No difference in graft survival between the two groups was noted: three out of nine patients in the PE-IVIG-RTX group(33.3%) and 4/12 in the control group(33.3%) experienced loss of allograft function at a median time after diagnosis of 14 mo(min 12-max 18) and 15 mo(min 7-max 22), respectively. Kidney functional tests and proteinuria 24 mo after cA MR diagnosis were also similar in both groups. Only microvascular inflammation(glomerulitis + peritubular capillaritis score) was significantly reduced after PE-IVIG-RTX in seven out of eight patients(87.5%) in the PE-IVIG-RTX group(median score 3 in pre-treatment biopsy vs 1.5 in post-treatment biopsy; P = 0.047), without any impact on kidney survival and/or DSA characteristics. No functional or histological parameter at diagnosis was predictive of clinical outcome.CONCLUSION Our data showed no difference in the two year posttreatment outcome of kidney grafts treated with PE-IVIGRTX for c AMR diagnosis, however there were notable improvements in microvascular inflammation in posttherapy protocol biopsies. Further studies, especially involving innovative therapeutic approaches, are required to improve the management and long-term results of this severe condition.展开更多
Pancreatic islet transplantation is a minimally invasive procedure aiming to reverse the effects of insulin deficiency in patients with type 1 diabetes(T1D)by transplanting pancreatic beta cells.Overall,pancreatic isl...Pancreatic islet transplantation is a minimally invasive procedure aiming to reverse the effects of insulin deficiency in patients with type 1 diabetes(T1D)by transplanting pancreatic beta cells.Overall,pancreatic islet transplantation has improved to a great extent,and cellular replacement will likely become the mainstay treatment.We review pancreatic islet transplantation as a treatment for T1D and the immunological challenges faced.Published data demonstrated that the time for islet cell transfusion varied between 2 and 10 h.Approximately 54%of the patients gained insulin independence at the end of the first year,while only 20%remained insulin-free at the end of the second year.Eventually,most transplanted patients return to using some form of exogenous insulin within a few years after the transplantation,which imposed the need to improve immunological factors before transplantation.We also discuss the immunosuppressive regimens,apoptotic donor lymphocytes,anti-TIM-1 antibodies,mixed chimerism-based tolerance induction,induction of antigen-specific tolerance utilizing ethylene carbodiimide-fixed splenocytes,pretransplant infusions of donor apoptotic cells,B cell depletion,preconditioning of isolated islets,inducing local immunotolerance,cell encapsulation and immunoisolation,using of biomaterials,immunomodulatory cells,etc.展开更多
BACKGROUND Cirrhosis results from persistent liver injury that leads to liver fibrosis.Immunological factors play important regulatory roles in the development and progression of cirrhosis.Bibliometrics is one of the ...BACKGROUND Cirrhosis results from persistent liver injury that leads to liver fibrosis.Immunological factors play important regulatory roles in the development and progression of cirrhosis.Bibliometrics is one of the most commonly used methods for systematic evaluation of a field of study.To date,there are no bibliometric studies on the role of immunological factors in cirrhosis.AIM To provide a comprehensive overview of the knowledge structure and research hotspots of immunological factors in cirrhosis.METHODS We retrieved publications related to immunological factors in cirrhosis between 2003 to 2022 from the Web of Science Core Collection database on December 7,2022.The search strategy was TS=((Liver Cirrhosis OR hepatic cirrhosis OR liver fibrosis)AND(Immunologic*Factor*OR Immune Factor*OR Immunomodulator*OR Biological Response Modifier*OR Biomodulator*)).Only original articles and reviews were included.A total of 2873 publications were analyzed using indicators of publication and citation metrics,countries,institutes,authors,journals,references,and keywords by CiteSpace and VOSviewer.RESULTS A total of 5104 authors from 1173 institutions across 51 countries published 2873 papers on cirrhosis and immunological factors in 281 journals.In the past 20 years,the increasing number of related annual publications and citations indicates that research on immunological factors in cirrhosis has become the focus of attention and has entered a period of accelerated development.The United States(781/27.18%),China(538/18.73%),and Germany(300/10.44%)were the leading countries in this field.Most of the top 10 authors were from the United States(4)and Germany(3),with Gershwin ME contributing the most related articles(42).World Journal of Gastroenterology was the most productive journal,whereas Hepatology was the most co-cited journal.Current research hotspots regarding immunological factors in cirrhosis include fibrosis,cirrhosis,inflammation,liver fibrosis,expression,hepatocellular carcinoma,activation,primary biliary cirrhosis,disease,and hepatic stellate cells.Burst keywords(e.g.,epidemiology,gut microbiota,and pathways)represent research frontiers that have attracted the interest of researchers in recent years.CONCLUSION This bibliometric study comprehensively summarizes the research developments and directions of immunological factors in cirrhosis,providing new ideas for promoting scientific research and clinical applications.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
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: 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
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
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
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
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
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
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
基金the Science and Technology Research Foundation of Liaoning Provincial Department of Education,No. 2008777
文摘BACKGROUND:Artificial materials composed of acellular heterogeneous nerves can resolve donor shortage problems for the repair of peripheral nerve defects.However,it remains unclear whether artificial materials can overcome immunological rejection of heterogeneous nerve grafts and obtain similar effects as allogeneic nerve grafts.OBJECTIVE:To analyze regeneration and immunological rejection of defective sciatic nerves in rats through the use of acellular heterogeneous nerve grafts.DESIGN,TIME AND SETTING:A randomized,controlled study was performed at the Department of Anatomy,China Medical University and the Experimental Center,First Affiliated Hospital,China Medical University between January and December 2008.MATERIALS:TritonX-100 (Sigma,USA) and deoxycholate (Pierce,USA) were used.METHODS:Bilateral sciatic nerves were collected from adult rabbits and treated with TritonX-100 and sodium deoxycholate to prepare acellular sciatic nerves,which were used to bridge 1-cm defective sciatic nerves in adult rats.MAIN OUTCOME MEASURES:The lymphocyte percentage in leukocytes was quantified following hemocyte staining.Neural regeneration and the recovery of motor end plates in the gastrocnemius muscle were observed under optical and electronic microscopy following toluidine blue staining,as well as acetylcholinesterase and succinate dehydrogenase histochemical staining.RESULTS:There was no significant difference in the lymphocyte percentage in leucocytes between transplanted and normal rats (P > 0.05).At 3 months after surgery,the rat toes on the operated side were separated and the rats could walk.In addition,the footplates exhibited an escape response when acupunctured.A large number of regenerated nerve fibers were observed in the transplant group,and acetylcholinesterase-positive motor end plates were visible in fibers of the gastrocnemius muscle.CONCLUSION:Acellular heterogeneous nerve transplants for the repair of defective sciatic nerves in rats promote neural regeneration without significant immunological rejection.
基金a grant from Ap-plied Basic Research Programof Jiangsu Department of Sci-ence and Technology, No.BS99062
文摘BACKGROUND: At present, it has been confirmed that immunological rejection exists in the cell transplantation in brain tissue, the effects of immunosuppressant on the immunological rejection and the survival of grafts in brain cell transplantation are worthy being investigated further. OBJECTIVE: To observe the immunological rejection after transgeneic cell transplantation in treating cerebral hemorrhage in rats, and investigate the interventional effect of cyclosprin. DESIGN: A randomized controlled study. SETTINGS: Second Affiliated Hospital of Xuzhou Medical College; First Affiliated Hospital of Nanjing Medical University. MATERIALS: Thirty-five healthy clean-degree SD rats of 6-8 weeks old were used, weighing 200-250 g, either male or female; The FACSort flow cytometer (American BD Company) and NYD-1000 image analytical system were used. The rat-anti-rat CD4 monoclonal antibody, rat-anti-rat CD8 monoclonal antibody, and rat-anti-rat MHC Ⅱ antigen monoclonal antibody were purchased from Santa Cruz Company; SP and DAB kits were purchased from Beijing Zhongshan Bio-engineering Company. XSP-8C2 light microscope was the product of Shanghai Zousun Optical Instrument, Co.,Ltd, and KYKY-3800B electron microscope was the product of China KYKY Technology Development Co.,Ltd. METHODS: The experiments were carried out in the animal experimental center of Nanjing Medical University from April to July in 2003. ① Model establishment: The rats were anesthetized, and then the coordinates of left internal capsule were identified, and the needle was withdrawn after 120 μL blood was injected into the internal capsule. Adenoviruses were taken as the carriers, after the astrocytes were successfully transfected by nerve growth factor(NGF) gene, 0.2 mL cell suspension was injected into the sites of cerebral hemorrhage. Thirty successfully established rat models were randomly divided into cyclosporin A group (n=18) and control group, the rats were treated with intraperitoneal injection of cyclosporin A (10 mg/kg per day) intraperitoneal injection of saline of the same dosage from the 1st day after transplantation, once a day for 7 days continuously. ② CD4+ and CD8+ detection: The CD4+ and CD8+ T lymphocytes in caudal vein were counted with flow cytometer at 15 days after treatment. ③ Morphological observation in the transplanted sites: The rats were killed and then brain tissues were taken out, the transplanted sites and the structure of the normal brain tissue around the transplanted sites were observed with light and electron microscopes. ④ Detections of the infiltration of T lymphocyte subsets and expression of major histocompatibility complex (MHC) Ⅱ antigen in the transplanted sites: The image analysis of immunohistochemical sections was performed with the image analytical system, and the integral optical density (IOD) was taken as the statistical value to observe the infiltration of T lymphocyte subsets and expression of MHCⅡ antigen in the transplanted sites, and the normal brain tissue around the transplanted sites were taken as controls. MAIN OUTCOME MEASURES: ① Countings of CD4+ and CD8+ in peripheral blood; ②Results of the morphological observation in the transplanted sites; ③ Infiltration of T lymphocyte subsets and expression of MHC Ⅱ antigen in the transplanted sites. RESULTS: Totally 35 rats were used, and 30 were successfully made into models, 5 died during the treatment, the other 25 were involved in the analysis of results. ① Results of CD4+ and CD8+ T lymphocytes in peripheral blood: The percentages of CD4+ and CD8+ T lymphocytes in the cyclosporin A group were (29.20±3.97)% and (20.65±2.02)%, respectively, which were obviously lower than those in the control group [(47.39±3.01)%, (28.30±2.36)%, t=4.983, 4.012, P < 0.05], and the CD4+/CD8+ ratio was obviously lower than that in the control group (1.41±0.86, 1.68±0.69, t=3. 871, P < 0.05). ② Morphological results in the transplanted sites: Under optical and electron microscopes, the survival region of the transplant was round, and it had an unobvious migration region with the normal brain tissues, the grafts had normal cellular form. Infiltrations of lymphocytes and monocytes were observed in both groups, and mainly located in the transplanted sites, and the expression of lymphocytes in the cyclosporin A group was markedly lower than that in the control group, and no above-mentioned changes were observed in the normal brain tissue around the transplanted sites. ③ Results of CD4+ and CD8+ T lymphocytes and expression of MHC Ⅱ antigen in the transplanted sites: The CD4+ and CD8+ T lymphocytes and expression of MHC Ⅱ antigen in the transplanted sites were observed in both groups. The IOD of CD4+ and CD8+ antigen positive cells in the cyclosporin A group were obviously lower than those in the control group (1.85±0.38, 1.44±0.33; 3.33±0.37, 2.64±0.56, t=4.122, 4.434, P < 0.05), and the IOD of MHC Ⅱ antigen positive cells was markedly lower than that in the control group (0.76±0.22, 0.98±0.24, t=3.885, P < 0.05). CONCLUSION: ① There is immunological rejection in brain tissue after the transplantation of NSC transgeneic glial cells. ② The immunosuppressant of cyclosporin A can reduce the immunological rejection after the cell transplantation.
基金Tianjin Municipal Science and Technology CommissionGrant number:043803411
文摘Objective:To establish the polytransgenic mice expressing the human HT and complement regulatory proteins (CRPs) and discuss their ability to resist the hyperacute rejection (HAR) and delayed xenograft rejection (DXR) of heterogenic transplantation. Methods:Transgenic mice were produced by microinjection to construct gene for human HT, delay acceleration factor (DAF) and/or CD59 into the male pronucleus of zygote. PCR and Southern blot were used to screen the positive transgenic mice. Flow cytometry (FCM) was used to detect the expression of HT, α-Gal and DAF or CD59 on the PBMCs of transgenic mice. The survival time and function of the heart of transgenic mice were determined by a modified Langendorff cardiac perfusion apparatus. The change of proteinosis on IgM、IgG、C3c and C9 from different cardiac vascular endothelial cells of transgenic mice were detected by immunohistochemistry. Results:HT,DAF or CD59 were highly expressed on the positive transgenic mice by FCM. The deposition of IgM、IgG、C3c or C9 in the cardiac vascular endothelial cells of the positive transgenic mice were decreased. The survival time and function of the heart of the co-transgenic mice with AB serum perfusion were significantly longer and higher than that of the single HT positive transgenic mice(P<0.05). Conclusion:The mice co-expressing HT/DAF or HT/CD59 couldresist the HAR,which was better than those expressing HT alone. It is feasible to use HT and CRPs co-transgenic methods to resist the HAR and DXR.
基金financially supported by the Key Project of Zhejiang Provincial Natural Science Foundation of China(LZ22C200003)the National Natural Science Foundation of China(32072290)。
文摘Histamine in food has attracted widespread attention due to the potential toxicity and associated health risk.However,its influences on immunological components,especially the function of key immune cells,are still poorly known.In this work,we explored the effects of exogenous histamine on the function of key immune cells such as intestinal epithelial cells,dendritic cells,and T cells.The results showed that histamine could affect the expression of allergy-related genes in CMT93 cells at a high dose of histamine.Moreover,it’s found that histamine could cause an imbalance in the levels of relevant immune factors secreted by dendritic cells and T cells,especially those related to allergy.At the same time,the proportion of MHC class IIpositive dendritic cells and the proportion of T helper 2(Th2)cells in CD4^(+)T cells increased after histamine stimulation.We concluded that the presence of a certain level of histamine in food may affect the expression of allergy-related cytokines,disrupt the balance of the immune homeostasis,and potentially lead to adverse immune reactions.This work demonstrated the importance of including the estimation of histamine’s immune safety in aquatic products rather than merely considering the potential risk of food poisoning.
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Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and management.It delves into host immune responses and reactivation’s delicate balance,spanning innate and adaptive immunity.Viral factors’disruption of this balance,as are interac-tions between viral antigens,immune cells,cytokine networks,and immune checkpoint pathways,are examined.Notably,the roles of T cells,natural killer cells,and antigen-presenting cells are discussed,highlighting their influence on disease progression.HBV reactivation’s impact on disease severity,hepatic flares,liver fibrosis progression,and hepatocellular carcinoma is detailed.Management strategies,including anti-viral and immunomodulatory approaches,are critically analyzed.The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation.In conclusion,this compre-hensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation.With a dedicated focus on understanding its implic-ations for disease progression and the prospects of efficient management stra-tegies,this article contributes significantly to the knowledge base.The more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches,ultimately enhancing disease management and elevating patient outcomes.The dynamic landscape of management strategies is critically scrutinized,spanning anti-viral and immunomodulatory approaches.The role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.
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.
文摘AIM To evaluate the role of a therapeutic regimen with plasma exchange, intravenous immunoglobulins and rituximab in chronic-active antibody-mediated rejection(c AMR) settings.METHODS We compared 21 kidney transplant recipients(KTRs) with a diagnosis of c AMR in a retrospective casecontrol analysis: nine KTRs treated with plasmapheresis, intravenous immunoglobulins and rituximab(PE-IVIGRTX group) vs 12 patients(control group) not treated with antibody-targeted therapies. We examined kidney survival and functional outcomes 24 mo after diagnosis. Histological features and donor-specific antibody(DSA) characteristics(MFI and C1 q-fixing ability) were also investigated.RESULTS No difference in graft survival between the two groups was noted: three out of nine patients in the PE-IVIG-RTX group(33.3%) and 4/12 in the control group(33.3%) experienced loss of allograft function at a median time after diagnosis of 14 mo(min 12-max 18) and 15 mo(min 7-max 22), respectively. Kidney functional tests and proteinuria 24 mo after cA MR diagnosis were also similar in both groups. Only microvascular inflammation(glomerulitis + peritubular capillaritis score) was significantly reduced after PE-IVIG-RTX in seven out of eight patients(87.5%) in the PE-IVIG-RTX group(median score 3 in pre-treatment biopsy vs 1.5 in post-treatment biopsy; P = 0.047), without any impact on kidney survival and/or DSA characteristics. No functional or histological parameter at diagnosis was predictive of clinical outcome.CONCLUSION Our data showed no difference in the two year posttreatment outcome of kidney grafts treated with PE-IVIGRTX for c AMR diagnosis, however there were notable improvements in microvascular inflammation in posttherapy protocol biopsies. Further studies, especially involving innovative therapeutic approaches, are required to improve the management and long-term results of this severe condition.
基金Supported by European Union-NextGenerationEU,through The National Recovery and Resilience Plan of the Republic of Bulgaria,No.BG-RRP-2.004-0008-C01.
文摘Pancreatic islet transplantation is a minimally invasive procedure aiming to reverse the effects of insulin deficiency in patients with type 1 diabetes(T1D)by transplanting pancreatic beta cells.Overall,pancreatic islet transplantation has improved to a great extent,and cellular replacement will likely become the mainstay treatment.We review pancreatic islet transplantation as a treatment for T1D and the immunological challenges faced.Published data demonstrated that the time for islet cell transfusion varied between 2 and 10 h.Approximately 54%of the patients gained insulin independence at the end of the first year,while only 20%remained insulin-free at the end of the second year.Eventually,most transplanted patients return to using some form of exogenous insulin within a few years after the transplantation,which imposed the need to improve immunological factors before transplantation.We also discuss the immunosuppressive regimens,apoptotic donor lymphocytes,anti-TIM-1 antibodies,mixed chimerism-based tolerance induction,induction of antigen-specific tolerance utilizing ethylene carbodiimide-fixed splenocytes,pretransplant infusions of donor apoptotic cells,B cell depletion,preconditioning of isolated islets,inducing local immunotolerance,cell encapsulation and immunoisolation,using of biomaterials,immunomodulatory cells,etc.
基金the National Multi-Center Clinical Research Project of Peking University First Hospital,No.2022CR57.
文摘BACKGROUND Cirrhosis results from persistent liver injury that leads to liver fibrosis.Immunological factors play important regulatory roles in the development and progression of cirrhosis.Bibliometrics is one of the most commonly used methods for systematic evaluation of a field of study.To date,there are no bibliometric studies on the role of immunological factors in cirrhosis.AIM To provide a comprehensive overview of the knowledge structure and research hotspots of immunological factors in cirrhosis.METHODS We retrieved publications related to immunological factors in cirrhosis between 2003 to 2022 from the Web of Science Core Collection database on December 7,2022.The search strategy was TS=((Liver Cirrhosis OR hepatic cirrhosis OR liver fibrosis)AND(Immunologic*Factor*OR Immune Factor*OR Immunomodulator*OR Biological Response Modifier*OR Biomodulator*)).Only original articles and reviews were included.A total of 2873 publications were analyzed using indicators of publication and citation metrics,countries,institutes,authors,journals,references,and keywords by CiteSpace and VOSviewer.RESULTS A total of 5104 authors from 1173 institutions across 51 countries published 2873 papers on cirrhosis and immunological factors in 281 journals.In the past 20 years,the increasing number of related annual publications and citations indicates that research on immunological factors in cirrhosis has become the focus of attention and has entered a period of accelerated development.The United States(781/27.18%),China(538/18.73%),and Germany(300/10.44%)were the leading countries in this field.Most of the top 10 authors were from the United States(4)and Germany(3),with Gershwin ME contributing the most related articles(42).World Journal of Gastroenterology was the most productive journal,whereas Hepatology was the most co-cited journal.Current research hotspots regarding immunological factors in cirrhosis include fibrosis,cirrhosis,inflammation,liver fibrosis,expression,hepatocellular carcinoma,activation,primary biliary cirrhosis,disease,and hepatic stellate cells.Burst keywords(e.g.,epidemiology,gut microbiota,and pathways)represent research frontiers that have attracted the interest of researchers in recent years.CONCLUSION This bibliometric study comprehensively summarizes the research developments and directions of immunological factors in cirrhosis,providing new ideas for promoting scientific research and clinical applications.
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.
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.
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.
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 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.
