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 investigate the clinical prognosis of the liver transplant recipients diagnosed with hepatocellular carcinoma (HCC) complicated with microvascular invasion (MVI). Methods Clinical data of 3 447 HCC recipients undergoing liver transplantation were extracted from Surveillance, Epidemiology, and End Results (SEER) database of American National Cancer Institute. According to the incidence of MVI, all recipients were divided into MVI (n=376) and non-MVI groups (n=3 071). The clinical prognosis of liver transplant recipients was statistically compared between two groups by analyzing the 1-, 3- and 5-year overall survival (OS) and liver cancer specific survival (LCSS). Relevant clinical data including age, gender, race, pathological staging, tumor size, lymph node metastasis, distant metastasis, tumor-node-metastasis (TNM) staging and MVI were recorded in two groups. The independent risk factors of clinical prognosis of HCC recipients undergoing liver transplantation were analyzed by multivariate Cox regression model. The nomogram for predicting the clinical prognosis of the recipients was delineated. The accuracy of the prediction model was evaluated by the consistency index. Results In the non-MVI group, the 1-, 3-, 5-year OS and LCSS were 93.5%, 82.1%, 75.3% and 98.3%, 93.8%, 90.7%, significantly higher than 88.8%, 72.1%, 68.4% and 95.3%, 83.1%, 80.4% in the MVI group (all P < 0.05). Multivariate regression analysis showed that pathological staging, tumor size, lymph node metastasis, distant metastasis, TNM staging and MVI were the independent risk factors of OS and LCSS in HCC recipients undergoing liver transplantation (all P < 0.05). The nomogram consistency index was calculated as 0.624 (0.602-0.648). Conclusions MVI is an independent risk factor of the clinical prognosis of HCC recipients undergoing liver transplantation, which is significantly correlated with poor prognosis of the recipients. The nomogram based on MVI can predict the clinical prognosis of these recipients.
ABSTRACT
Objective To investigate the donor-related risk factors for long-term biliary complications after liver transplantation (LT) from organ donation by citizens after death.Methods The clinical data of 140 donors who donated the organs after death for LT in the Third Affiliated Hospital of Sun Yat-sen University between April 2016 and April 2017 were retrospectively analyzed.The incidence of long-term biliary complications after LT in the recipients was observed,and the relationship between the incidence and the clinical indexes of the donors was analyzed.The influencing factors for long-term biliary complications after LT were analyzed using univariate and multivariate logistic regression analysis.Results The incidence of long-term biliary complications after LT in the recipients was 9.29％ (13/140).The incidence of donation after cardiac death (DCD) group and donation after brain death (DBD) group was 9.68％ (6/62) and 8.97％ (7/78) respectively.There was no significant difference between the two groups.Univariate logistic regression analysis revealed the long-term biliary complications after LT was related with cerebrovascular accident cause,the second warm ischemia time,steatosis of liver,history of cardiopulmonary resuscitation,dosage of dopamine before procurement and hypoproteinemia.Multivariate logistic regression analysis (removing warm ischemia time) revealed the independent influencing factors for long-term biliary complications after LT from organ donation were the second warm ischemia time (OR =1.106,95％ CI:1.034-1.181;P＜0.05),steatosis of liver (OR =5.319,95％ CI:1.020-27.752;P＜0.05) and dosage of dopamine before procurement (OR =1.279,95％ CI:1.021-1.601;P ＜ 0.05).Conclusion Postoperative long-term biliary complication is one of the major complications after LT from organ donation.The independent risk factors should be strictly controlled,as the second warm ischemia time,steatosis of liver and dosage of dopamine before procurement are contributed to the incidence of long-term biliary complications.