1.Carbon monoxide-releasing molecule CORM-2 protects against renal ischemia-reperfusion injury in mice
Yongle RUAN ; Lu WANG ; Yue ZHAO ; Junxiang WANG ; Song CHEN ; Changsheng MING ; Gang CHEN
Chinese Journal of Organ Transplantation 2013;34(11):685-689
Objective To investigate if the administration of CORM-2 can provide protection against renal ischemia-reperfusion injury (IRI).Method Murine renal ischemia was induced by clamping left renal pedicles for 40 min with vascular micro damps at 32 C,then the contralateral kidney was removed.CORM-2 or vehicle was administered via intravenous infusion 1 h before the onset of ischemia.The blood plasma and renal samples were obtained at 24 h after reperfusion to assess renal function and cellular injury.Plasma Cr and BUN levels,HE and TUNEL were performed to estimate the magnitude of renal damage.Kidneys were retrieved from indicated animals at various time points after renal IRI,and the sections were prepared for histological evaluation.MPO staining procedures were performed to assess the neutrophils infiltration in the renal IRI.Besides,Immunofluorescent stain of TNF-α was performed on the kidneys which were retrieved from indicated animals to determine the production of inflammatory mediators in renal I/R.Results The plasma Cr and BUN were significantly increased at 24 h after reperfusion in IRI control mice,and CORM-2 treatment could markedly diminish the increase of plasma Cr and BUN in mice subjected to I/R.In parallel,histological analysis demonstrated that CORM2 treatment markedly reduced apoptosis of the renal tubular epithelium cells and hemorrhage.IRI caused marked infiltration and accumulation of the MPO-positive neutrophils in renal interstitium.Administration of CORM-2 before ischemia dramatically inhibited neutrophils infiltration as compared with IRI or iCORM-2 group.Furthermore,we confirmed that CORM-2 markedly decreased production of TNF-α.Conclusion Carbon monoxidereleasing molecule CORM-2 could ameliorate inflammation to protect against the renal IRI in mice.
2.Using mice immature dendritic cells to induce the differentiation of allogenic naive T cells in vitro
Yue ZHAO ; Lu WANG ; Yongle RUAN ; Xiaoxiao WANG ; Ying XIANG ; Junxiang WANG ; Gang CHEN
Chinese Journal of Organ Transplantation 2014;35(2):117-120
Objective To explore the differentiation of allogeneic naive T cells to regulatory T cells (Tregs) and T helper (TH) 1/2/17 cells by coculture with bone marrow-derivedimmature dendritic cells (irnDC).Method Bone marrow-derived imDC were cultivated from Balb/c mice.Lipopolysaccharide-stimulated DC were harvested as mature dendritic cells (mDC) and unstimulated cells were collected as imDC.Then irnDC or mDC were cocultured with allogeniec naive T cells,respectively.TH1 cytokines [interferon-γ (IFN-γ) and interleukin (IL)-2],TH2 cytokines (IL-4 and IL-10),and TH17 cytokine (IL-17) of co-cultured cells were detected by enzyme linked immunospot assay.CD4+ Forkhead box p3 (FoxP3) + Treg proportion in CD4+ cells in the co-cultured system with IL-2 and transforming growth factor-β1 (TGF-β1) was analyzed by flow cytometry.Result As compared with mDC,na(i)ve T cells cocultured with imDC secreted much less IFN-γ (11.67 ± 2.18 vs.182.00±23.71,P<0.01),IL-2 (26.67±2.96 vs.318.30± 18.62,P<0.01),IL-4 (17.00±3.78 vs.45.33±3.48,P<0.01),IL-10(7.00±1.00vs.158.70±10.90,P<0.001) and IL-17 (0.66 ± 0.33 vs.238.30 ± 24.39,P<0.001).Furthermore,imDC induced more CD4+ FoxP3+ Tregs than mDC after adding IL-2 and TGF-β1 in the coculture system for 7 days (22.70 ± 1.53 % vs.5.42 ± 1.27%,P<0.01).Conclusion imDC are more effective to induce na ve T cells to Tregs,but not differentiate to TH 1/TH 2/TH 17 cells.These findings provide in vitro experimental evidence for induction of transplant tolerance by adoptive transfer of imDC.
3.Resistance of rat adipose-derived stem cells to human xenoantibody-dependant complement-mediated lysis and its mechanism
Yue ZHAO ; Lu WANG ; Yongle RUAN ; Xiaoxiao WANG ; Yu JIA ; Ying XIANG ; Gang CHEN
Chinese Journal of Organ Transplantation 2014;35(6):370-373
Objective To investigate whether rat adipose-derived stem cells (rASCs) could resist human xenoantibody-dependent complement-mediated lysis and to explore its possible mechanisms.Method SD rat ASCs were isolated,rASCs at passage 2 to 8 were used for the following studies and rat lymphocytes were harvested as control cells.α-Gal expression was detected by flow cytometry.After incubation of rASCs with 20% normal human serum (NHS) or heat inactivated normal human serum (HINHS),flow cytometry was used to detect cytotoxicity,IgG or IgM binding,and C3c,C4c and C5b-9 deposition.Result We successfully established the method to isolate and culture rASCs.The morphology of rASCs remained unchanged after passages.rASCs were positive for tell surface markers of CD44 and CD90,while negative for CD45 and MHC-Ⅱ.As compared with rLCs,rASCs significantly resisted human natural antibody and complement-mediated lysis when incubated with 20% NHS in vitro (20.42% ± 2.80% vs 51.84% ± 6.70%,P < 0.01).Mechanistically,rASCs expressed lower level of α-Gal (13.97 ± 0.33 vs.24.47 ± 3.03,P<0.05),which was correlated with decreased binding of human xenoreactive IgG and IgM (IgM:9.4 ± 2.0 vs.107.2± 4.8,P<0.01; IgG:5.73 ± 1.0 vs.27.49 ± 3.9,P<0.01) and reduced deposition of complements C3c,C4c and C5b-9 (C3c:294.6 ± 38.02 vs.1924 ± 509.4,P<0.05; C4c:35.23 ± 3.1vs.177.3 ± 37.17,P<0.05; C5b-9:5.63 ± 1.74 vs.37.05 ± 7.4,P<0.01).Conclusion These data demonstrated that the resistance of rASCs to human xenoantibody and complement-mediated lysis is associated with low expression of xenoantigen a-Gal and inhibition of MAC (membrane attack complex) formation.
4.Prolongation of islet allograft survival in rats by cotransplantion with xenogenetic neonatal porcine Sertoli cells
Yongle RUAN ; Zhuzeng YIN ; Junhua LI ; Ying XIANG ; Hui GUO ; Shan ZHONG ; Qiong ZHONG ; Xiaowei GUO ; Shi CHEN ; Gang CHEN
Chinese Journal of Organ Transplantation 2009;30(12):740-744
Objective To investigate whether cotransplant with xenogenetic neonatal porcine Sertoli cells (NPSCs) could prolong rat islet allograft survival and its mechanisms.Methods 1500 islets equivalent quantity (IEQ) and 1×10~7 NPSCs were implanted under renal capsule of diabetic Wistar rats.Islets implanted alone were used as control group (n=6);islets co-transplanted with NPSCs under left renal capsule of recipients served as experimental group (n=6);meanwhile,islets and NPSCs implanted into the different sides of kidneys were used as another control grouP(n=4).Blood glucose level was measured everyday.The graft-bearing kidneys at the time of rejection were Results Co-transplantation with NPSCs to the same site significantly prolonged islet allograft survival (mean survive time,16.3±1.4 days vs.5.7±1.0 days in islet transplant alone control group,P<0.05).In contrast,transplantation with NPSCs and islets separately did not prolong the islet allograft survival (5.3±0.5 days).HE staining showed plenty of local infiltrated lymphocytes in the transplanted site of the eontrol group.which were demonstrated as mainly CD3+ T cells by immunopathology.The local expression of Bcl-2 was markedly elevated in co-transplantation group as compared with the other 2 groups,while there were no significant differences in the HO-1 expression among these groups.Conclusion Co-transplantation with xenogenic NPSCs can significantly prolong islet allograft survival in rats.The immunoprotective mechanism may be associateel with the inhibition of lymphocyte infiltration and the enhancement of the local expression of protective gene Bcl-2.
5.Clinical analysis of type A aortic dissection with acute lower limb ischemia
Wei REN ; Zhiwei WANG ; Zhiyong WU ; Jinxing CHANG ; Yongle RUAN ; Jiahui WANG
Chinese Journal of Thoracic and Cardiovascular Surgery 2019;35(3):154-158
Objective To summarize the clinical experience and efficacy of surgical treatment for Stanford type A aortic dissection leading to acute lower limb ischemia.Methods From January 2014 to January 2018,12 patients with severe lower limb ischemia caused by acute type A aortic dissection were treated with Suns surgery.Among them,11 patients were treated with restoration of lower limb blood supply preferentially,including 10 cases of femoral artery bypass and 1 case of abdominal aorta-iliac artery stent graft implantation.Another case was treated with ascending aorta-femoral artery bypass after Sung surgery.Results 3 cases died of ischemia and necrosis of the lower extremities.Two of them died of multiple organ failure due to amputation and one died of low cardiac output due to refractory acidosis.Acute renal failure performed bedside CRRT in 5 patients and ECMO in 1 patient.The remaining 9 patients were discharged from the hospital and the symptoms of lower limb ischemia disappeared.After an average follow-up of 23 months,the re-examination of the aorta CTA showed that the bypass artery was unobstructed and the distal femoral artery was well developed.One patient infecting vascular prosthesis was cured by taking out the unit.Conclusion For acute lower limb ischemia caused by type A aortic dissection,blood flow of lower extremities should be restored as soon as possible to reduce mortality and complications.Femoral artery bypass and abdominal aorta-iliac arterial repair are simple and effective in reconstructing lower limb blood supply.
6.Clinical application of 3D printing-assisted extracorporeal fenestration in TEVAR surgery
Zhiyong WU ; Jincheng HOU ; Xuekai LIU ; Jingyuan WEN ; Rui HU ; Yongle RUAN
Chinese Journal of Thoracic and Cardiovascular Surgery 2022;38(10):586-589
Objective:To investigate the effectiveness and feasibility of 3D printing-assisted extracorporeal fenestration techniques in thoracic aortic endoluminal repair.Methods:Retrospectively analyzed the clinical data of patients who underwent endovenous repair of the thoracic aorta with the application of 3D printing technology-assisted extracorporeal windowing in the Department of Cardiovascular Surgery, Wuhan University Hospital from January 2019 to May 2021, and analyzed the surgical results as well as the occurrence of perioperative complications.Results:A total of 10 patients with a mean age of(53.3±15.7) years were included, including 4 cases of complex B aortic coarctation, 5 cases of thoracic aortic aneurysm and 1 case of abdominal aortic aneurysm. All patients in this group underwent endoluminal repair of the thoracic aorta with 3D printing assisted extracorporeal fenestration, including 1 case of PCI performed at the same time. There were no postoperative complications and no perioperative deaths.Conclusion:3D printing technology assisted extracorporeal fenestration and endoluminal aortic repair can accurately position aortic stents for fenestration, optimise endoluminal treatment options and improve patient prognosis.
7.Research advances of cardiac graftvasculopathy
Ruiqi SANG ; Aoxue WANG ; Yihan TANG ; Zhiyong WU ; Yongle RUAN
Chinese Journal of Organ Transplantation 2023;44(11):698-702
From the perspectives of the pathogenesis, diagnosis and treatment of cardiac graft vasculopathy(CGV), this review summarized the current understanding and cognition of its pathology, monitoring, diagnosis and treatment to provide rationales for better survivals of CGV.
8.Recent advance in pathogenesis and treatments of neurological complications related to patent foramen ovale
Aoxue WANG ; Yihan TANG ; Ruiqi SANG ; Zhiyong WU ; Yongle RUAN
Chinese Journal of Neuromedicine 2023;22(12):1282-1286
Patent foramen ovale (PFO) is the most prevalent congenital heart disease, often accompanied by neurological symptoms as migraine, unexplained dizziness, and even anxiety and depression. Recent research findings indicate that the pathogenesis of neurological complications related to PFO involves abnormal embolism hypothesis, vasoactive substance hypothesis, impaired cerebral blood flow regulation and genetic inheritance. Treatments include primarily encompass pharmacological intervention and foramen ovale occlusion. This article summarizes the aforementioned research progress in order to provide clinical guidance for managing nervous system complications related to PFO.
9.Single-center effect analysis of clinical application of marginal donor heart
Zhiyong WU ; Zhiwei WANG ; Zongli REN ; Yongle RUAN ; Wei REN ; Rui HU ; Anfeng YU ; Feng SHI ; Yifan ZUO
Chinese Journal of Thoracic and Cardiovascular Surgery 2020;36(4):222-226
Objective:To retrospectively analyze the experience of our center in the use of marginal donor heart, and to explore the principle of use and risk control of marginal donor heart.Methods:A total of 31 patients with end-stage heart disease underwent orthotopic heart transplantation in our center from January 2018 to December 2018, including 28 cases of pure heart transplantation, 2 cases of combined heart-lung transplantation, and 1 case of combined heart-kidney transplantation. 26 of the 31 cases were marginal donor hearts. These patients were all anastomosed by a double lumen method.Results:The rates of postoperative use of ECMO, IABP and acute rejection were zero in this study. The time of cardiopulmonary bypass in the marginal donor group was significantly longer compared with the conventional donor group( P<0.05), but there was no significant difference between the two groups in terms of hospitalization time, mechanical ventilation time, ICU stay time, abnormal rate of ECG, LVEF and blood biochemical indexes(all P>0.05). The postoperative follow-up rate was 100% in the two groups. One case of combined heart-lung transplantation in the marginal donor group died of multiple organ failure in the first month after surgery. During the postoperative follow-up period, the incidence of moderate to severe tricuspid regurgitation and the incidence of recurrent heart failure were zero in the two groups. There was no significant difference in the incidence of arrhythmia, LVEF, infection and blood biochemical parameters. Conclusion:The application of marginal donor heart has no significant effect on the short-term survival rate and recovery of patients after heart transplantation, but the long-term effect needs further follow-up.
10.Comparison and enlightenment of cardiothoracic residency training between China and the United States
Chinese Journal of Medical Education Research 2023;22(1):128-132
Through the comparison of the residency training system between China and the United States in pre-training educational background, training policy and post-training career path, it is concluded that the cardiothoracic surgery residency training in the United States has a high admission threshold, long training cycle and high education cost, but it also has the advantages of professional management, outstanding specialty characteristics and perfect evaluation system, which are suitable for the training of cardiothoracic surgeons. However, the current residency training of cardiothoracic surgery in China needs to be further improved. Learning from the advantages of the United States residency training system, we can formulate a more reasonable and professional residency training program according to Chinese own characteristics, so as to train excellent cardiothoracic surgeons for our country.