ABSTRACT
Objective To investigate the role and mechanism of circular RNA SNRK (circSNRK) in ischemia-reperfusion injury (IRI). Methods A hypoxia-reoxygenation (IRI) cell model was established. The expression level of circSNRK after IRI treatment and the effect of overexpression of circSNRK on cell proliferation and apoptosis were detected. The targets of circSNRK were identified. HK2 cells were divided into the blank group (Mock group), IRI group, control plasmid+IRI group (IRI+NC group), human circSNRK overexpression+IRI group (IRI+circSNRK group), human circSNRK overexpression+IRI+protein kinase B (Akt) inhibitor group (IRI+circSNRK+MK2206 group) and control plasmid group (NC group). Cell proliferation and apoptosis were detected in the Mock, IRI, IRI+NC and IRI+circSNRK groups. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the target of circSNRK were carried out. The expression levels of CDKN1A, Akt, B-cell lymphoma (Bcl)-2, cysteinyl aspartate specific proteinase (Caspase)-9 messenger RNA (mRNA), and those of p21, Bcl-2, Caspase-9, Akt and p-Akt proteins were detected in the Mock, IRI, IRI+NC and IRI+circSNRK groups, respectively. Cell proliferation and apoptosis were determined in the NC, IRI+NC, IRI+circSNRK and IRI+circSNRK+MK2206 groups. Results Compared with the Mock group, the expression level of circSNRK was lower, and cell proliferation capability of HK2 cells was decreased and cell apoptosis was increased in the IRI group. In the IRI+circSNRK group, cell proliferation capability was higher, whereas cell apoptosis was lower than those in the IRI+NC group. circSNRK could act on 648 targets through 51 microRNAs (miRNAs). GO enrichment analysis revealed that the targets of circSNRK were mainly enriched in biological processes (such as cell process and biological regulation), cell components (such as cell parts, cells and extracellular parts), and molecular functions (such as binding, binding proteins and enzymes). KEGG enrichment analysis showed that the targets of circSNRK were mainly enriched in cancer signaling pathway, phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway, miRNA in cancer and other related signaling pathways. Compared with the Mock group, the relative expression levels of CDKN1A and Caspase-9 mRNA were higher, the expression level of miR-99a-5p RNA was higher and the relative expression levels of Akt and Bcl-2 mRNA were lower in the IRI group. Compared with the IRI+NC group, the relative expression levels of CDKN1A and Caspase-9 mRNA were lower, those of Akt and Bcl-2 mRNA were higher, and the expression level of miR-99a-5p RNA was lower in the IRI+circSNRK group, and the differences were statistically significant (all P < 0.05). Compared with the Mock group, the expression levels of p21 and Caspase-9 proteins were higher, while those of p-Akt, Akt and Bcl-2 proteins were lower in the IRI group. Compared with the IRI+NC group, the expression levels of p21 and Caspase-9 proteins were lower, whereas those of p-Akt, Akt and Bcl-2 proteins were higher in the IRI+circSNRK group. The miR-99a-5p binding sites were observed in circSNRK and Akt. Compared with the NC group, cell proliferation capability was declined in the IRI+NC group. Compared with the IRI+NC group, cell proliferation capability was elevated in the IRI+circSNRK group. Compared with the IRI+circSNRK group, cell proliferation capability was declined in the IRI+circSNRK+MK2206 group (all P < 0.05). The cell apoptosis level in the IRI+NC group was higher than that in the NC group. The cell apoptosis level in the IRI+circSNRK group was lower compared with that in the IRI+NC group. The cell apoptosis level in the IRI+circSNRK+MK2206 group was higher than that in the IRI+circSNRK group. Conclusions Under IRI conditions, circSNRK may affect the proliferation and apoptosis of HK2 cells probably via the Akt signaling pathway.
ABSTRACT
Objective To evaluate the clinical efficacy of percutaneous transluminal angioplasty (PTA) combined with stent implantation in the treatment of transplant renal artery stenosis (TRAS) after renal transplantation. Methods Clinical data of 21 patients with TRAS after renal transplantation undergoing PTA combined with stent implantation were retrospectively analyzed. The incidence of TRAS in renal transplant recipients was summarized. The changes of relevant indexes in patients with TRAS were statistically compared before and after interventional treatment. Clinical prognosis of patients with TRAS was evaluated. Results The incidence of TRAS in renal transplant recipients was 4.1%(21/507). TRAS was diagnosed at postoperative 5 (4, 7) months, and 67% (14/21) of patients developed TRAS within postoperative 6 months. Compared with the values before interventional therapy, the serum creatinine level, systolic and diastolic blood pressure and peak flow velocity of transplant renal artery of patients with TRAS were significantly decreased, and the estimated glomerular filtration rate (eGFR) and interlobar arterial resistance index were significantly increased at 1 week and 1 month after interventional therapy (all P < 0.05). During postoperative follow-up after PTA combined with stent implantation, 1 patient suffered re-stenosis of the transplant renal artery, which was improved after simple balloon dilatation. One patient developed pseudoaneurysm formation at the puncture site of the right femoral artery. One patient presented with renal atrophy and loss of function due to atresia of the transplant renal artery. All the remaining 18 patients were well recovered after surgery. Conclusions PTA combined with stent implantation is the optimal treatment of TRAS after renal transplantation, which can significantly improve the function of transplant kidney and considerably prolong the survival time of transplant kidney.
ABSTRACT
Objective To evaluate the effect of conversion from mycophenolic acid (MPA) to mizoribine (MZR) in renal transplant recipients with gastrointestinal tract (GI) symptoms.Methods A total of 355 renal transplant recipients with GI symptoms caused by MPA administration were enrolled from April 2015 to March 2017 in 25 different renal transplant centers in China.The symptomatic improvement of GI before (baseline) and after conversion to MZR (1,2,4 weeks) was assessed by each item of GI symptoms indication.In addition,the efficacy and safety of the conversion therapy during 12 months were determined.Results Patients showed improvement in GI symptoms including diarrhea,abdominal pain,abdominal distention and stomachache after conversion to MZR 1,2,4 weeks (P＜0.05).In patients with different severity of diarrhea,conversion to MZR therapy significantly improved diarrhea (P＜0.05).During 12 months,no patient experienced clinical immune rejection.We did not observe any infections,leucopenia and other serious side effects.Conclusion MZR could markedly improve GI symptoms caused by MPA administration in renal transplant recipients.
ABSTRACT
Objective A new field of organ donation after cardiac death (DCD) has been explored to create additional source to clinic transplantation in China.Methods A 33-years old male patient underwent permanent vegetation state for more than 2 years in ICU after severe head injury.His relatives gave writing consent to donate his organs in order to save his renal failure father and others,if possible,in case of cardiac death.On July 27,2005,the patient's heart arrested.Clinic death was announced.The case was immediately referred to transplant team and Maastricht-V DCD organ procurement was emergently performed and two kidneys were harvested. Estimated warm ischemic time was about 40 min followed by 8 h cold ischemic time.Two adults received the grafts.One of recipients was donor's biological father,namely it was the first case of deceased related renal transplantation (DRRTx) in China.Results Both recipients developed delayed graft function postoperatively and eventually recovered after few weeks.By submission of this article,the DRRTx patient has survived with normal renal function for 77 months (6 years and 5 months).Unfortunately,other patient died from fungus pneumonia after 56 months with normal renal function.Conclusion Non-controlled Maastricht-V DCD could be an additional source to transplantation if prompt reaction could be taken.
ABSTRACT
Objective To analyze the outcome of allograft function of the HBsAg(+) recipients and discuss the suitable time of antiviral therapy. Methods Twenty-one HBsAg(+) recipients were randomly divided two groups: one group (11 cases) taking lamivudine orally after recovery of intestinal function, and another group (10 cases) taking lamivudine orally when liver dysfunction and increased HBV-DNA (HBV-DNA>106 copies/L) occurred during the period of follow-up. Liver function, allograft function, and hepatitis virus reactivation were followed up for 2 years after transplantation. Results Hepatitis recurrence and liver dysfunction after renal transplantation lay in viral replication after immuno-suppression. Lamivudine therapy accomplished the goals of viral suppression, and normalization of alanine aminotransferase (ALT) levels. Preemptive lamivudine therapy for recipients had a better liver and allograft function than oral administration for patients with liver dysfunction and increased HBV-DNA copies during a period of the two-years follow-up. Conclusion HBsAg (+) is not contraindication of renal transplantation. Preemptive lamivudine therapy early after operation could avoid liver dysfunction and improve the renal allograft function during the period of two-years follow-up.
ABSTRACT
Objective To evaluate the role of the combination of angiotensin receptor blocker (ARB)and angiotensin corwerting enzyme inhibitor(ACEI)in functional protection and long-term survival of renal allograft. Methods Thirty-two renal transplant recipients without diabetes mellitus,whose albuminuria concentration in 24-hours collection was more than 0.5 g/d or serum Cr concentration was higher than 177 mmol/L,were randomly divided into experimental group(n=23,male 9 and female 14 cases,mean age 40 years)and control group(n=9,male 5 and female 4 cases,mean age 35 years).Combination of ARB(Valsartan,80rag Qd)and ACEI(Benazapril,20 mg Bid)theraPy was given to each patient every day for 3 years in experimental group.The recipients in control group never received this administration.The serum Cr concentration,albuminuria in 24-hours collection and survival of renal allograft were compared between the 2 groups after 3 years. Results There was significant difference(P＜0.05) of serum Cr concentration between experimental group and control group(252.2±117.9 mmol/L VS 375.3±203.0 mmol/L),especially for chronic allograft nephropathy (CAN)patieats(282.4±147.3 mmol/L vs 528.7±107.8 mmol/L,P＜0.01).There was no difference (P＞0.05)in terms of the values of alburninuria(1.0±0.6 g/d vs 1.3±0.7 g/d)and survival of renal allograft(76 months VS 71 months)after 3 years between 2 groups.Comclusion The administration of ARB+ACEI could protect function of renal allograft with different pathological changes especially for CAN.
ABSTRACT
AIM: To study the clinical treatments and prognosis of the severe pneumonia in 12 patients after renal transplantation. METHODS: Twelve patients with severe pneumonia following renal transplantation treated in Guangdong Provincial Hospital of Traditional Chinese Medicine were selected between May 2004 and October 2006. They all agreed to the experiment. Seven patients had pneumonia at 3 months after transplantation, 1 at 3.5 months, 3 at 4 months and 1 at 5 months. The main therapy included immunosuppressive removal at early stage, mask oxygen inhalation, bi-level airway pressure ventilation or tracheal intubation to correct the hypoxemia; the algogen was detected by many approaches, and specific treatment was carried out according to the susceptibility test; gastroenteric nutrition was supplied through nasogastric tube, and part patients were given parenteral nutrition to strengthen nutrition support. Imaging examination of lung and blood gas analysis were performed every two to three days to evaluate the curative effect; transplanted kidney function was detected to determine the acute rejection early. RESULTS: All 12 patients were involved in the result analysis without any lost. Etiological agent detection: There were three cases with fungal pneumonia, 4 with cytomegalovirus pneumonia, 3 with bacterial pneumonia, 1 with mixed infection and 2 with unclear agent. Two cases of cytomegalovirus pneumonia developed rapidly into acute respiratory distress in 1 week after hospitalization and finally died of respiratory failure; the rest 10 patients were rescued successfully, except one with pulmonary interstital fibrosis, which could affect the life quality. CONCLUSION: The key points of successful treatment for severe pneumonia are the combination of early aggressive reduction of the immunosuppressive therapy, early detection of responsible pathogen and effective control of severe hypoxemia.
ABSTRACT
Objective:To investigate the pahtogengesis and pathology of delayed xenograft rejection (DXR) after pig to rhesus monkey heart xenotransplantation.Methods:Heterotopic xenogeneic heart transplantation in the abdominal cavity was performed using piglet as donors.4 monkeys were used as recipients.Complete complement depletion was achieve in the recipients treated with repetitive doses of a high activity cobra venom factor (Y CVF).The recipients were immunosuppressed with a combination of cyclosporine A,cyclophosphamide and steroids.Sera were analyzed for C3,C4 levels and complement activity and anti pig endotheliocyte xenoantibody.The graft were examined histopathologically and immunohistochemically for C3,C4,C5b 9,IgM,IgG,necrosis factor alpha (TNF alpha),intercellular adhesion molecule 1 (ICAM 1),CD57 (NK cells),CD68 (macrophages),CD4 and CD8.Results:The xenografts survived 8,10,13,13 days respectively and all grafts occoured DXR.Venular thrombosis was outstanding feature within DXR xenografts,complicated with interstitial edma,local hemorrhage and myocardial necrosis,with mild to moderate cellular infiltration.The serum C3 levels and complement activity almost decreased to 0 from the day of transplantation due to Y CVF,the C4 level began to decrease 2 4 days before the cardic xenografts losing their function.The anti pig endotheliocyte xenoantibody also decreased after transplantation,and slightly increased during DXR,all rejected xenografts showed C3,C4,C5b 9,IgG and IgM deposits in different degree.Large numbers of macrophages (50% of total leukocytes) were found infiltrating the entire xenograft,a few natural killer cells (8%～10%),some of CD4+T cells (15%) and CD8+T cells (25%) were detcted also,up regulation of ICAM 1 on the graft endothelial cells and TNF alpha in the interstitial were demonstrated in the rejected heart.Conclusion:Both Humor and cell mediated immunologic reaction may play an important role in pahtogengesis of DXR. [