BACKGROUND: Long non-coding RNAs (lncRNAs) play important roles in cancer development, yet their roles in renal carcinoma remain unclear. OBJECTIVE: We performed this study in order to investigate the expression and roles of lncRNAs in renal cell carcinoma. METHODS: In this study, we investigated the expression of lncRNAs in renal cell carcinoma through microarray analysis. Quantitative real-time PCR was performed to measure the expression of lncRNAs. Gain- or loss-of-function experiments were performed to investigate the roles of lncRNAs in cell proliferation and apoptosis. RNA pull-down and western blotting were performed to explore the underlying mechanism. RESULTS: The microarray analysis identified an upregulated lncRNA MIR4435-1HG in renal carcinoma. The expression level of MIR4435-1HG was correlated with TNM stage, tumor size, and Fuhrman grade. High expression of MIR4435-1HG indicated poor prognosis. MIR4435-1HG knockdown inhibited cell proliferation, and suppressed the migrating and invasive capacity of renal carcinoma cells. RNA pull-down followed by mass spectrometry revealed an interaction between MIR4435-1HG and pyruvate carboxylase, which was later corroborated by western blotting. CONCLUSIONS: MIR4435-1HG plays a critical role in the oncogenesis of renal cell carcinoma and may serve as a potential biomarker for renal cell carcinoma.
Delayed graft function (DGF) is a risk factor for acute rejection and graft failure after kidney transplant. Previous studies have suggested that dexmedetomidine may be renoprotective, but whether the use of dexmedetomidine would improve kidney allograft function is unknown.
Objective
To investigate the effects of perioperative dexmedetomidine on DGF following a donation-after-cardiac-death (DCD) kidney transplant.
Design, Setting, and Participants
This single-center, double-blind, placebo-controlled randomized clinical trial was conducted at The First Affiliated Hospital of Soochow University in Suzhou, China. Adults (18 years or older) who were scheduled for DCD kidney transplant were enrolled between September 1, 2019, and January 28, 2021, and then randomized to receive either dexmedetomidine or normal saline (placebo). One-year postoperative outcomes were recorded. All analyses were based on the modified intention-to-treat population.
Interventions
Patients who were randomized to the dexmedetomidine group received a 24-hour perioperative dexmedetomidine intravenous infusion (0.4 μg/kg/h intraoperatively and 0.1 μg/kg/h postoperatively). Patients who were randomized to the normal saline group received an intravenous infusion of the placebo with the same dose regimen as the dexmedetomidine.
Main Outcomes and Measures
The primary outcome was the incidence of DGF, defined as the need for dialysis in the first posttransplant week. The prespecified secondary outcomes were in-hospital repeated dialysis in the first posttransplant week, in-hospital acute rejection, and serum creatinine, serum cystatin C, estimated glomerular filtration rate, need for dialysis, and patient survival on posttransplant day 30.
Results
Of the 114 patients enrolled, 111 completed the study (mean [SD] age, 43.4 [10.8] years; 64 male patients [57.7%]), of whom 56 were randomized to the dexmedetomidine group and 55 to the normal saline group. Dexmedetomidine infusion compared with normal saline reduced the incidence of DGF (17.9% vs 34.5%; odds ratio [OR], 0.41; 95% CI, 0.17-0.98;P = .04) and repeated dialysis (12.5% vs 30.9%; OR, 0.32; 95% CI, 0.13-0.88;P = .02, which was not statistically significant after multiple testing corrections), without significant effect on other secondary outcomes. Dexmedetomidine vs normal saline infusion led to a higher median (IQR) creatinine clearance rate on postoperative days 1 (9.9 [4.9-21.2] mL/min vs 7.9 [2.0-10.4] mL/min) and 2 (29.6 [9.7-67.4] mL/min vs 14.6 [3.8-45.1] mL/min) as well as increased median (IQR) urine output on postoperative days 2 (106.5 [66.3-175.6] mL/h vs 82.9 [27.1-141.9] mL/h) and 7 (126.1 [98.0-151.3] mL/h vs 107.0 [82.5-137.5] mL/h) and at hospital discharge discharge (110.4 [92.8-121.9] mL/h vs 97.1 [77.5-113.8] mL/h). Three patients (5.5%) from the normal saline group developed allograft failure by the post hoc 1-year follow-up visit.
Conclusions and Relevance
This randomized clinical trial found that 24-hour perioperative dexmedetomidine decreased the incidence of DGF after DCD kidney transplant. The findings support the use of dexmedetomidine in kidney transplants.
Trial Registration
Chinese Clinical Trial Registry Identifier:ChiCTR1900025493
// Cheng Chen 1, * , Zhen Chen 1, * , Kun Wang 1 , Linkun Hu 2 , Renfang Xu 1 and Xiaozhou He 1 1 Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, P.R. China 2 Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P.R. China * These authors contributed equally to this work Correspondence to: Renfang Xu, email: xrfmnwk@163.com Xiaozhou He, email: hxzmnwk@163.com Keywords: prostatic neoplasms, prostatectomy, radiotherapy, quality of life Received: August 21, 2017 Accepted: September 22, 2017 Published: October 05, 2017 ABSTRACT The objective of this study is to compare health-related quality of life (QOL) outcomes between radical prostatectomy (RP) and external beam radiation therapy (EBRT) for localized prostate cancer. PubMed, EMBASE, the Cochrane Library and Web of Science (to July 2017) were searched. Pooled analysis of each domain-specific score was calculated in relevant studies, and its change with follow-up time was explored by sub-group analysis. A total of six studies containing 4423 patients were included. Men underwent RP was associated with worse urinary and sexual domain score than EBRT (standardized mean difference (SMD) = –0.59, –0.58; 95% confidence interval (CI) = –0.73 to –0.45, –0.72 to –0.44). In contrast, EBRT group had lower bowel domain score than RP group (SMD = 0.42, 95% CI = 0.33 to 0.52). The sub-group analysis revealed the most severe urinary and sexual QOL in RP as well as bowel QOL in EBRT group all happened in the first month post operation. The different performance of two treatments in three QOL domains diminished afterwards. Health-related QOL should be considered comprehensively when planning follow-up for men after RP or EBRT for localized prostate cancer.
The aim of the study was to evaluate the predictive value of preoperative high-sensitive C-reactive protein/albumin (hs-CRP/Alb) ratio in systemic inflammatory response syndrome (SIRS) after percutaneous nephrolithotomy (PCNL).We retrospectively reviewed 556 patients who underwent PCNL at our institution between August 2015 and February 2018. The primary endpoint for the study was the development of SIRS after operation. A univariate and multivariate logistic regression analysis was used to identify the independent factors associated with the post-PCNL SIRS. Receiver operating characteristic (ROC) curves were constructed and the areas under the curve (AUC) were calculated to compare the discriminatory ability of systemic inflammation biomarkers.Among the 556 patients who underwent PCNL, 123 patients (22.1%) developed SIRS. Multivariate analysis revealed that female gender (OR 1.691; 95% CI 1.045-2.735; p = 0.032), positive urine culture (OR 1.972; 95% CI 1.204-3.231; p < 0.01), hs-CRP/Alb ratio (OR 6.925; 95% CI 4.244-11.300; p < 0.01), neutrophil to lymphocyte ratio (NLR) (OR 2.476; 95% CI 1.471-4.167; p < 0.01), and prognostic nutritional index (PNI) (OR 0.559; 95% CI 0.338-0.924; p = 0.023) were independent predictors of post-PCNL SIRS. The optimal cutoff value of the hs-CRP/Alb ratio was 0.06 from the ROC analysis. The elevated hs-CRP/Alb ratio was significantly associated with female gender, positive urine culture, hs-CRP, albumin, leukocyte, neutrophil, monocyte, platelet, hemoglobin, creatinine, NLR, lymphocyte to monocyte ratio (LMR), platelet to lymphocyte ratio (PLR), PNI, high-sensitive modified Glasgow prognostic score (hs-mGPS), development of sepsis, ICU admission, and length of stay (all p < 0.05). In addition, the hs-CRP/Alb ratio had a higher AUC (0.791) with a sensitivity of 76.4% and a specificity of 73.2% than NLR (0.669), LMR (0.633), PLR (0.594), PNI (0.629), and hs-mGPS (0.739).The preoperative hs-CRP/Alb ratio is independently predictive for the development of SIRS after PCNL. Moreover, compared with other systemic inflammation biomarkers, the preoperative hs-CRP/Alb ratio shows a better predictive value.
Objective To improve the diagnosis and treatment of chromophobe renal cell carcinoma (CRCC),we investigated and summarized the clinical and pathological features of CRCC patients in our hospital.Methods We have retrospectively analyzed the clinical features of 33 CRCC patients.The mean age of these patients at diagnosis was 55 years-old,including 13 males and 20 females.All tumors were localized unilaterally,with 18 in left kidney and 15 in right kidney.Ultrasonography was performed on all patients,CT scan on 30 patients and MRI on 3 patients.Results All of the patients underwent surgery.Fifteen patients underwent radical nephrectomy,11 patients underwent laparoscopic radical nephrectomy,5 patients underwent nephron sparing surgery and 2 patients underwent laparoscopic nephron sparing surgery.The average diameter of tumors was 5.2 cm.Among them,23 patients were at pT1N0M0,6 at pT2N0M0,2 at T3N0M0 and 2 at T3N0M0.The pathologic Fuhrman grade of CRCC was G1 in 1 case,G2 in 19 cases,G3 in 9 cases and G4 in 4 cases.Twenty-six patients were followed up with a mean duration of 24 months and no local recurrence was found.Conclusions CRCC is a rare subtype of renal cell carcinoma with little recurrence and metastasis.Surgery was the common treatment for CRCC.Usually,CRCC patients have favorable prognosis.
Key words:
Carcinoma, renal cell; Chromophobe cell carcinoma; Diagnosis; Treatment; Prognosis
Abstract Background. We performed the first clinical trial in China in which kidney transplantation was combined with donor hematopoietic stem cell (DHSC) infusion for tolerance induction. This study summarizes the 10-year follow-up results. Methods. From 2009 to 2017, 11 cases of living-related kidney transplantation combined with DHSC infusion were performed. Two of them were HLA-matched, and nine were HLA-mismatched. The DHSCs were mobilized using granulocyte colony-stimulating factor and harvested one day before transplantation. The recipients received consecutive total lymphoid irradiation for 3 days before kidney transplantation. The induction drug was anti-thymocyte globulin. DHSCs were infused on the 2 nd , 4 th and 6 th postoperative days. Results. One HLA-matched recipient induced 30-50% chimerism, and the others only induced less than 1% chimerism. Recipients had a low immune response to their donors while sustaining normal reactivity to non-donors in mixed lymphocyte reactions. All recipients were followed up for 717~3,918 days. One recipient lost allograft function, and 10 recipients had stable renal function. None of the 11 recipients had myelosuppression or graft-versus-host disease post transplantation. Our protocol did not increase the risk of infection. Allograft biopsy confirmed that one patient had mild acute rejection, and the other 10 recipients did not develop rejection. Five patients reduced the dose of immunosuppression. Conclusions. This study shows that long-term stable kidney allograft survival may be achieved with low-dose immunosuppression maintenance using our protocol. Trial registration: Chinese Clinical Trial Registry, ChiCTR-TNC-09000399. Registered 22 April 2009 - Retrospectively registered, http://www.chictr.org.cn
Antibody-mediated rejection (AMR) represents a major cause of allograft dysfunction and results in allograft failure in solid organ transplantation. Cyclic helix B peptide (CHBP) is a novel erythropoietin-derived peptide that ameliorated renal allograft rejection in a renal transplantation model. However, its effect on AMR remains unknown. This study aimed to investigate the effect of CHBP on AMR using a secondary allogeneic skin transplantation model, which was created by transplanting skin from BALB/c mice to C57BL/6 mice with or without CHBP treatment. A secondary syngeneic skin transplantation model, involving transplantation from C57BL/6 mice to C57BL/6 mice, was also created to act as a control. Skin graft rejection, CD19 + B cell infiltration in the skin allograft, the percentages of splenic plasma cells, germinal center (GC) B cells, and Tfh cells, the serum levels of donor specific antibodies (DSAs), and NF- κ B signaling in splenocytes were analyzed. Skin allograft survival was significantly prolonged in the CHBP group compared to the allogeneic group. CHBP treatment also significantly reduced the CD19 + B cell infiltration in the skin allograft, decreased the percentages of splenic plasma cells, GC B cells, and Tfh cells, and ameliorated the increase in the serum DSA level. At a molecular level, CHBP downregulated P100, RelB, and P52 in splenocytes. CHBP prolonged skin allograft survival by inhibiting AMR, which may be mediated by inhibition of NF- κ B signaling to suppress B cell immune responses, thereby decreasing the DSA level.
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