Robust fault diagnosis with disturbance rejection and attenuation for systems with multiple disturbances

The fault diagnosis problem is investigated for a class of nonlinear neutral systems with multiple disturbances.Time-varying faults are considered and multiple disturbances are supposed to include the unknown disturbance modeled by an exo-system and norm bounded uncertain disturbance.A nonlinear disturbance observer is designed to estimate the modeled disturbance.Then,the fault diagnosis observer is constructed by integrating disturbance observer with disturbance attenuation and rejection performances.The augmented Lyapunov functional approach,which involves the tuning parameter and slack variable,is applied to make the solution of inequality more flexible.Finally,applications for a two-link robotic manipulator system are given to show the efficiency of the proposed approach.

Diagnosis and treatment of acute rejection in the first case of human living-related small bowel transplantation with a long-term survival in China

AIM： To report the comprehensive diagnosis and treatment of acute rejection in the first case of living-related small bowel transplantation with a long-term survival in China. METHODS： A 18-year-old boy with short gut syndrome underwent living-related small bowel transplantation, with the graft taken from his father （44-year old）. A segment of 150-cm distal small bowel was resected from the donor. The ileo-colic artery and vein from the donor were anastomosed to the infrarenal aorta and vena cava of the recipient respectively. The intestinal continuity was restored with an end-to-end anastomosis between the recipient jejunum and donor ileum, and the distal end was fistulized. FK506, MMF and prednisone were initially used for post-transplant immunosuppression. Endoscopic observation and mucosal biopsies of the graft were carried out through the terminal ileum enterostomy; serum was collected to detect the levels of IL-2R, IL-4, IL-6 and IL-8. The change of the graft secretion and absorption was observed. RESULTS： Acute rejection was diagnosed promptly and cured. The patient was in good health, 5 years after living- related small bowel transplantation. CONCLUSION： The correct diagnosis and treatment of acute rejection are the key to the long-term survival after living-related small bowel transplantation.

Role for urinary biomarkers in diagnosis of acute rejection in the transplanted kidney

Despite the introduction of potent immunosuppressive medications within recent decades, acute rejection still accounts for up to 12% of all graft losses, and is generally associated with an increased risk of late graft failure. Current detection of acute rejection relies on frequent monitoring of the serum creatinine followed by a diagnostic renal biopsy. This strategy is flawed since an alteration in the serum creatinine is a late clinical event and significant irreversible histologic damage has often already occurred. Furthermore, biopsies are invasive procedures that carry their own inherent risk. The discovery of non-invasive urinary biomarkers to help diagnose acute rejection has been the subject of a significant amount of investigation. We review the literature on urinary biomarkers here, focusing on specific markers perforin and granzyme B m RNAs, FOXP3 m RNA, CXCL9/CXCL10 and mi RNAs. These and other biomarkers are not yet widely used in clinical settings, but our review of the literature suggests that biomarkers may correlate with biopsy findings and provide an important early indicator of rejection, allowing more rapid treatment and better graft survival.

Proteomics for rejection diagnosis in renal transplant patients: Where are we now?

Rejection is one of the key factors that determine the long-term allograft function and survival in renal transplant patients. Reliable and timely diagnosis is important to treat rejection as early as possible. Allograft biopsies are not suitable for continuous monitoring of rejection. Thus, there is an unmet need for non-invasive methods to diagnose acute and chronic rejection. Proteomics in urine and blood samples has been explored for this purpose in 29 studies conducted since 2003. This review describes the different proteomic approaches and summarizes the results from the studies that examined proteomics for the rejection diagnoses. The potential limitations and open questions in establishing proteomic markers for rejection are discussed, including ongoing trials and future challenges to this topic.

Donor liver natural killer cells alleviate liver allograft acute rejection in rats

BACKGROUND:Liver enriched natural killer (NK) cells are of high immune activity.However,the function of donor liver NK cells in allogeneic liver transplantation (LTx) remains unclear.METHODS:Ten Gy of whole body gamma-irradiation (WBI) from a 60 Co source at 0.6 Gy/min was used for depleting donorderived leukocytes,and transfusion of purified liver NK cells isolated from the same type rat as donor (donor type liver NK cells,dtl NKs) through portal vein was performed immediately after grafting the irradiated liver.Post-transplant survival observation on recipients and histopathological detection of liver grafts were adoptive to evaluate the biological impact of donor liver NK cells on recipients’ survival in rat LTx.RESULTS:Transfusion of dtl NKs did not shorten the survival time among the recipients of spontaneous tolerance model (BN to LEW rat) after rat LTx,but prolonged the liver graft survival among the recipients depleted of donor-derived leukocytes in the acute rejection model (LEW to BN rat).Compared to the recipients in the groups which received the graft depleted of donor-derived leukocytes,better survival and less damage in the allografts were also found among the recipients in the two different strain combinations of liver allograft due to transfusion of dtl NKs.CONCLUSIONS:Donor liver NK cells alone do not exacerbate liver allograft acute rejection.Conversely,they can alleviate it,and improve the recipients’ survival.

Metronomic capecitabine inhibits liver transplant rejection in rats by triggering recipients’T cell ferroptosis

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.

EXPRESSION OF ICAM-1 AND LFA-1 MOLECULES IN RELATION TO RENAL ALLOGRAFT REJECTION IN RATS

Objective.The purpose of this study was to assess the renal graft expression of ICAM 1(intercellular adhesion molecule 1) and LFA 1(lymphocyte function associated antigen 1)molecule with relation to graft rejection. Methods.Rat kidney transplantation was performed according to the procedure of Kamada with some modification.Experimental rats were divided into 5 groups.The survival time of recipient rats and function of grafts after renal transplantation were observed.The sections of renal graft were stained for monoclonal antibody ICAM 1 and LFA 1, and then quantification of ICAM 1 and LFA 1 expression was accomplished by computer image analysis. Results.ICAM 1 and LFA 1 increased significantly in the renal allograft rejection group as compared with the non rejection groups(P<0 05). Conclusion.Both biopsy of renal graft and monitoring of ICAM 1 and LFA 1 are useful tools in diagnosing and treating acute rejection.

Studies on the Effects of the Immunosuppressant FK-506 on the High-risk Corneal Graft Rejection

Purpose: To evaluate the clinical efficacy of FK-506 on suppressing high-risk cornea transplantation rejection.Methods: In a randomized controlled clinical trial, 56 eyes of 56 patients with high-risk keratoplasty (including total corneal transplantation TCT, total corneal transplantation with circular lamellar sclera CST, vascularization corneal transplantation and corneal retransplantation) were divided into the experimental group and the control group(each with 28 eyes).The experimental group was treated by FK-506 eyedrops (0.5 mg/ml) and TobraDex eyedrops, compared with the control group that was treated by 1% CsA eyedrops and TobraDex eyedrops. In the average 8.1-month follow-up period, the visual acuity, graft transparent duration and Rejection Index (RI) of grafts were observed. Results: In the follow-up period, the graft rejection rate of the experimental and the control group was 63.6% and 95.2% respectively (χ2＝4. 72, P ＜ 0. 05) with significant difference.Conclusions: The local application of FK-506 suppressed effectively the graft rejection of corneal transplantation of the patients at high risk.

Lymphocyte infiltration and activation in iris-ciliary body and anterior chamber of mice in corneal allograft rejection

AIM: To investigate the infiltration and activation of lymphocyte in iris-ciliary body and anterior chamber after allogenic penetrating keratoplasty (PK), for further revealing the role of iris-ciliary body in corneal allograft immune rejection. METHODS: In the mice models of PK, BALB/C mice received orthotopic isografts (n =35) or C57BL/6 donor allografts (n=25). Grafts were examined daily for 3 weeks by slit-lamp microscopy and scored for opacity. The infiltration of CD4(+) T lymphocyte in iris-ciliary body and anterior chamber was examined by immunohistology and the mRNA of CD80 and CD86 in both cornea graft and iris-ciliary body by RT-PCR was analyzed in allograft recipient at days 3, 6, 10 and the day when graft rejection occurred. Isograft recipients were examined as control at the corresponding time points. Transmission electron microscope was used to study the ultrastructure, especially cell infiltration, of iris-cilary body and corneal graft at day 3, 7 and the day when rejection occurred after allogenic PK. RESULTS: Rejection was observed in all the allograft recipients followed more than 10 days, at a median time of 15 days (range 12-18 days), but not in any of isografts. CD4(+) T cells were first detected at day 6 after transplantation in limbus and Ciliary body, and then in the stroma of recipient, iris, anterior chamber and corneal allograft with an increased number until graft rejection occurred. CD80 and CD86 mRNA were detected under RT-PCR examination in both graft and iris-ciliary body of allograft recipient, but not in any of isograft recipient. Three days after operation, lymphocytes and monocytes macrophages were visible in iris blood vessels and the anterior chamber, and vascular endothelial cell proliferation and activation were significant under transmission electron microscopy examination. At day 7, corneal endothelial cells became thinner. Lymphocytes and mononuclear macrophages were found with great number in the anterior chamber and adhered to the corneal endothelium. Blood vessels in iris increased and were filled with lymphocytes. And lymphocytes were detected to migrate through endothelial cell gap out of vessels. When allograft rejection occurred, macrophages attached to endothelial cells with large number of lymphocytes and macrophages infiltrating in iris. CONCLUSION: Lymphocyte infiltration and activation occurred in iris-ciliary body after allogenic PK, and the lymphocytes could migrate from iris blood vessel to the anterior chamber, which might play an important role in corneal allograft immune rejection.

Role of biliary complications in chronic graft rejection after living donor liver transplantation

Postoperative biliary complications remain a substantial challenge after living donor liver transplantation,especially due to its heterogeneous clinical presentation.

Noninvasive tools based on immune biomarkers for the diagnosis of central nervous system graft-vs-host disease:Two case reports and a review of the literature

BACKGROUND Central nervous system graft-vs-host disease(CNS-GVHD)is a rare cause of CNS disorders after allogeneic hematopoietic stem cell transplantation.Currently,establishing a diagnosis of CNS-GVHD is challenging because the diagnostic criteria and diagnostic methods are not well defined and many confounding factors need to be ruled out.CASE SUMMARY Here,we present two patients with CNS-GVHD.Both patients with a history of acute GVHD or chronic GVHD developed neurological symptoms that could not be explained by other causes,and had abnormal cerebrospinal fluid(CSF)studies as determined by CSF and blood immune biomarker examinations,suggestive of suspected CNS-GVHD.Due to the lack of specific magnetic resonance imaging abnormalities and the rapid clinical deterioration of the patients,we did not attempt to perform a brain biopsy,but prompted the initiation of empirical immunosuppressive therapy.In view of the rapid and favorable response to local and systematic immunosuppressive treatment and the aforementioned neurologic manifestations together with CSF abnormalities and other negative findings,a final diagnosis of CNS-GVHD was made.CONCLUSION CSF and blood immune biomarker examinations facilitated the diagnosis of CNSGVHD,which are particularly suitable for patients who are critically ill and require urgent treatment and for those who are unsuitable for invasive diagnostic procedures.

Preservation of donor's heart and lung and discrimination and postoperative immunotherapy of graft rejection:a report of 2 cases of heart-lung transplantation

Objective To summarize preservation measures of donor’s heart and lung,and postoperative imrnunotherapy,as well as clinical experience of discrimination and management for graft rejection. Methods Clinical data of 2 cases of heart - lung transplantation in our depart-

Chronic rejection after liver transplantation:Opening the Pandora’s box

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.

Mycophenolate Mofetil with Low Dose CsA for Chronic Rejection in Primary Cadaveric Renal Recipients

Objective To investigate the clinical efficacy of mycophenolate mofetil(MMF) with low dose CsA for chronic rejection in primary cadaveric renal recipients. Methods A total of 8 renal recipients who were clinically diagnosed as chronic rejection were given triimmunosuppressive agents: MMF 1.5~2.0 g/d+ CsA 2 to 3 mg/kg·d -1 and pred 10 mg/d.Results Blood creatinine reduced to normal level and urine protein disappeared in five cases, blood creatinine and urine protein decreased obviously in two cases, and kidney function deteriorated in another patient 4 to 9 weeks after this strategy. No acute rejection episodes or liver damage occurred among these patients during treatment. White blood cells reduced in one case, but it improved after therapy. Conclusion MMF combined with low dose CsA can bring a considerable efficacy in reversing chronic rejection of renal recipients. This immunosuppressive strategy may be a useful routine in the treatment of chronic rejection.

Correlation between tumor necrosis factor a gene promoter polymorphisms and acute rejection following renal transplantation

Objective To study the significance of cytokine tumor necrosis factor α ( TNF -α) gene promoter 308 position polymorphisms in predicting acute graft rejection following renal transplantation. Methods In 35 preoperative recipients, TNF-α produced by peripheral blood cells was measured by enzyme-linked immmunosorbent assay, and their TNF- α gene promoter 308 position polymorphisms were determined by FOR restriction fragment length polymorphisms(PCR-RFLP). The assocication between TNF-α gene promoter polymorphisms and production of them was studied. Furthermore, the correlation between their polymorphisms and acute rejection in the first 3 months after renal transplantation was discussed. Results The recipients with A/A or A/G genotype in TNF-α promoter 308 position secreted more cytokine (624.96 ± 177.78) pg/ml and (544.32 ± 13.242)pg/ml than those with G/G(233.16 ± 25.37)pg/ml,P【0.01. When HLA-DR was mismatched, the recipients with high production of TNF - α genotype showed higher incidence

Novel Fault Diagnosis Scheme for HVDC System via ESO

A novel fault detection and identification(FDI)scheme for HVDC(High Voltage Direct Current Transmission)system was presented.It was based on the unique active disturbance rejection concept,where the HVDC system faults were estimated using an extended states observer(ESO).Firstly,the mathematical model of HVDC system was constructed,where the system states and disturbance were treated as an extended state.An augment HVDC system was established by using the extended state in rectify side and converter side,respectively.Then,a fault diagnosis filter was established to diagnose the HVDC system faults via the ESO theory.The evolution of the extended state in the augment HVDC system can reflect the actual system faults and disturbances,which can be used for the fault diagnosis purpose.A novel feature of this approach is that it can simultaneously detect and identify the shape and magnitude of the HVDC faults and disturbance.Finally,different kinds of HVDC faults were simulated to illustrate the feasibility and effectiveness of the proposed ESO based FDI approach.Compared with the neural network based or support vector machine based FDI approach,the ESO based FDI scheme can reduce the fault detection time dramatically and track the actual system fault accurately.What's more important,it needs not do complex online calculations and the training of neural network so that it can be applied into practice.

成人再次肝移植研究进展

再次肝移植是肝移植术后移植肝衰竭的唯一治愈性手段。首次肝移植与再次肝移植间隔时间的长短,将直接影响成人再次肝移植的手术适应证、技术难度和治疗转归。既往多项研究认为再次肝移植术后移植肝及受者总体生存率明显低于首次肝移植,但随着器官保存方法、麻醉管理理念、重症监护策略、外科手术技术和新型免疫抑制药等各个领域的全面进步,成人再次肝移植的疗效显著提高。本文就成人再次肝移植手术适应证的变迁、手术时机的选择、长期疗效及其影响因素、手术技术难点、免疫抑制方案的选择以及活体再次肝移植的开展情况进行评述,总结目前成人肝移植取得的成果、面临的挑战及潜在解决方案,以期为提高成人再次肝移植的临床疗效提供参考。

中国肾脏移植受者移植物功能延迟恢复临床诊疗指南

肾移植受者移植物功能延迟恢复是肾脏移植术后常见的早期并发症之一,是影响移植肾近期和远期存活的独立危险因素。中华医学会器官移植学分会和中国医疗保健国际交流促进会肾脏移植学分会组织国内器官移植与相关学科知名专家在《肾移植术后移植物功能延迟恢复诊疗技术规范(2019版)》的基础上经过指南范围及临床问题的确定、证据检索与筛选及推荐意见的形成等程序编写、多轮讨论,并经学会组织两轮集体审定,最终形成《中国肾脏移植受者移植物功能延迟恢复临床诊疗指南》。本指南就移植肾功能延迟恢复的概念和发生机制、危险因素、诊断、预防、治疗及免疫抑制药应用几个方面的21个临床问题提出推荐意见和推荐意见说明。目的是使肾移植术后受者移植物功能延迟恢复的诊断、预防和治疗规范化,提高肾脏移植效果,提高肾脏移植受者和移植肾近期和长期存活率,促进移植学科的发展。

肺移植术后需要临床干预的气道狭窄患者生存结局的影响因素

目的分析肺移植术后需要临床干预的气道狭窄患者生存结局的影响因素。方法回顾性分析肺移植术后需要临床干预的66例气道狭窄患者的临床资料。采用单因素和多因素Cox回归模型分析所有气道狭窄患者和早期气道狭窄患者生存结局的影响因素,采用Kaplan-Meier法计算总生存率并绘制生存曲线。结果66例气道狭窄患者,中位无气道狭窄时间为72(52,102)d,27%(18/66)发生中心气道狭窄,73%(48/66)发生远端气道狭窄。术后机械通气时间[风险比(HR)1.037,95%可信区间(CI)1.005~1.070,P=0.024]和手术类型(HR 0.400,95%CI 0.177~0.903,P=0.027)均与肺移植术后气道狭窄患者的生存结局存在相关性,术后机械通气时间越长,受者死亡风险越高;接受双肺移植的气道狭窄患者的总生存率优于单肺移植。在亚组分析中,3级原发性移植物失功(PGD)(HR 4.577,95%CI 1.439~14.555,P=0.010)和免疫抑制药(HR 0.079,95%CI0.022~0.287,P<0.001)与肺移植术后早期气道狭窄患者生存结局均存在相关性;无3级PGD的肺移植术后早期气道狭窄患者的总生存率优于有3级PGD的患者,使用他克莫司的肺移植术后早期气道狭窄患者的总生存率优于使用环孢素的患者。结论术后机械通气时间长、单肺移植手术方式、3级PGD和使用环孢素可能影响肺移植术后气道狭窄患者的生存。

重庆春见和沃柑果园叶片黄化原因分析

重庆忠县、长寿和铜梁等地由甜橙高接换种的春见和沃柑,存在叶片黄化问题。为找出叶片黄化的主要原因,采集高换春见和沃柑正常园和黄化园的土壤和叶片样品,比较土壤理化性状、叶片矿质元素含量及叶片SPAD值,并对土壤理化性状、叶片SPAD值与叶片矿质营养的关系进行分析。结果表明,春见黄化园土壤pH均值(8.09)比正常园(6.89)显著高出17.42%,土壤有效铁含量(均值)显著低于正常园,交换性钙含量显著高于正常园,叶片铁含量显著低于正常园。沃柑黄化园土壤交换性钙含量高于正常园,有效铁含量显著低于正常园,叶片氮、硫、铁含量均值显著低于正常园。叶片SPAD值分别与叶片氮和叶片铁含量呈显著正相关,增强回归树分析显示叶片铁含量对叶片SPAD的贡献度最高(35.23%),其次为氮(22.29%)。排除自然灾害或病害等因素后,认为高换杂柑叶片黄化是因为土壤pH值和交换性钙较高,导致土壤有效铁含量降低,并抑制树体对Fe的吸收,最终引起叶片缺Fe黄化;另外,叶片N含量较低是导致沃柑黄化的因素之一。