Modified Y-V plasty based on MRU evaluation for iatrogenic bladder outlet obliteration: a multicentre experience in China.

PURPOSE: To compare the diagnostic ability of traditional radiographic urethrography and magnetic resonance urethrography (MRU) for iatrogenic bladder outlet obliteration (BOO), and explore the efficacy and complications of laparoscopic modified Y-V plasty for patients selected based on MRU evaluation. METHODS: 31 patients with obliteration segments ≤ 2 cm and no false passages or diverticula based on MRU evaluation from eight centers in China were included. Obliteration segments were measured preoperatively by MRU and conventional RUG/VCUG and compared with intra-operative measurements. Surgical effects were evaluated by uroflow rates, urethrography, or cystoscopy at 1, 3, 6, and 12 months post-operation and then every 12 months. Postoperative urinary continence was assessed by 24-h urine leakage (g/day). RESULTS: The results showed that MRU measured the length of obliteration more accurately than RUG/VCUG (MRU 0.91 ± 0.23 cm, RUG/VCUG 1.72 ± 1.08 cm, Actual length 0.96 ± 0.36 cm, p < 0.001), and clearly detected false passages and diverticula. Laparoscopic Y-V plasty was modified by incisions at 5 and 7 o'clock positions and double-layer suture with barbed sutures. All operations were successfully completed within a median time of 75 (62-192) minutes and without any complications. Urethral patency and urinary continence rates were 90.3% (28/31) and 87.1% (27/31), respectively. Three recurrences were cured by direct visual internal urethrotomy. Four patients had stress urinary incontinence after catheter removal 14 days post-operation, with urine leakage of 80-120 g/day, not relieved during follow-up. CONCLUSIONS: Laparoscopic modified Y-V plasty based on MRU evaluation is a promising approach for iatrogenic BOO, with a high patency rate and a low incontinence rate.

A prognostic risk prediction model based on ferroptosis-related long non-coding RNAs in bladder cancer: A bulk RNA-seq research and scRNA-seq validation.

BACKGROUND: To construct a prognostic risk model of bladder cancer (BC) from the perspective of long non-coding RNAs (lncRNAs) and ferroptosis, in order to guide clinical prognosis and identify potential therapeutic targets. METHODS: In-hours BC samples were collected from 4 patients diagnosed with BC, who underwent radical cystectomy. Single cell transcriptome sequencing was performed and Seurat package were used for quality control and secondary analysis. LncRNAs expression profiles of BC samples were extracted from The Cancer Genome Atlas database. And sex, age, tumor, node, metastasis stage and other clinical data was downloaded at the same time. Ferroptosis-related lncRNAs were identified by co-expression analysis. We constructed a risk model by Cox regression and least absolute shrinkage and selection operator regression analyses. The predictive strength of the risk model for overall survival (OS) of patients with BC was evaluated by the log-rank test and Kaplan-Meier method. Finally, the enrichment analysis was performed and visualized. RESULTS: We identified and included 15 prognostic ferroptosis-related lncRNAs (AL356740.1, FOXC2AS1, ZNF528AS1, LINC02535, PSMB8AS1, AL590428.1, AP000347.2, OCIAD1-AS1, AP001347.1, AC104986.2, AC018926.2, LINC00867, AC099518.4, USP30-AS1, and ARHGAP5-AS1), to build our ferroptosis-related lncRNAs risk model. Using this risk model, BC patients were divided into high and low-risk groups, and their respective survival lengths were calculated. The results showed that the OS of the low-risk group was significantly longer than that of the high-risk group. A nomogram was utilized to predict the survival rate of BC patients. As indicated in the nomogram, risk score was the most important indicator of OS in patients with BC. The ferroptosis-related lncRNAs risk model is an independent tool for prognostic risk assessment in patients with BC. Single cell transcriptome sequencing suggests that ferroptosis-related lncRNAs express specifically in BC tumor microenvironment. AL356740.1, LINC02535 and LINC00867 were mainly expressed in tumor cells. CONCLUSION: The risk model based on the ferroptosis-related lncRNAs and the genomic clinico-pathological nomogram could be used to accurately predict the prognosis of patients with BC. The lncRNAs used to build this model might become potential therapeutic targets in the future.

Expert consensus on clinical trials of human xenotransplantation in China.

The history of xenotransplantation started in the 19th century. After a few decades of investigation, significant breakthroughs and preclinical milestones have been achieved worldwide. With the recent transplantation of genetically modified porcine kidneys and heart into humans, these ground-breaking achievements have attracted great attention worldwide, in the hope that xenotransplantation might alleviate or even solve the problem of organ shortage. On January 20, 2022, the China Organ Transplantation Development Foundation convened a symposium on "The History, Current Situation and Future of Human Xenotransplantation Clinical Trials," where ways to promote the ethical and sustainable development of xenotransplantation in China were discussed among the participating experts. A formal consensus was reached as the product of the symposium, outlining the expert opinions on scientific, regulatory, and ethical issues of clinical trials of xenotransplantation in China.

Ischaemia-free liver transplantation in humans: a first-in-human trial.

Background Ischaemia-reperfusion injury is considered an inevitable component of organ transplantation, compromising organ quality and outcomes. Although several treatments have been proposed, none has avoided graft ischaemia and its detrimental consequences. Methods Ischaemia-free liver transplantation (IFLT) comprises surgical techniques enabling continuous oxygenated blood supply to the liver of brain-dead donor during procurement, preservation, and implantation using normothermic machine perfusion technology. In this non-randomised study, 38 donor livers were transplanted using IFLT and compared to 130 conventional liver transplants (CLT). Findings Two recipients (5•3%) in the IFLT group experienced early allograft dysfunction, compared to 50•0% in patients receiving conventional transplants (absolute risk difference, 44•8%; 95% confidence interval, 33•6-55•9%). Recipients of IFLT had significantly reduced median (IQR) peak aspartate aminotransferase levels within the first week compared to CLT recipients (365, 238-697 vs 1445, 791-3244 U/L, p<0•001); likewise, median total bilirubin levels on day 7 were significantly lower (2•34, 1•39-4•09 mg/dL) in the IFLT group than in the CLT group (5•10, 1•90-11•65 mg/dL) (p<0•001). Moreover, IFLT recipients had a shorter median intensive care unit stay (1•48, 0•75-2•00 vs 1•81, 1•00-4•58 days, p=0•006). Both one-month recipient (97•4% vs 90•8%, p=0•302) and graft survival (97.4% vs 90•0%, p=0•195) were better for IFLT than CLT, albeit differences were not statistically significant. Subgroup analysis showed that the extended criteria donor livers transplanted using the IFLT technique yielded faster post-transplant recovery than did the standard criteria donor livers transplanted using the conventional approach. Interpretation IFLT provides a novel approach that may improve outcomes, and allow the successful utilisation of extended criteria livers. Funding This study was funded by National Natural Science Foundation of China, Guangdong Provincial Key Laboratory Construction Projection on Organ Donation and Transplant Immunology, and Guangdong Provincial international Cooperation Base of Science and Technology. Panel: Research in context.

Single-center experience of organ transplant practice during the COVID-19 epidemic.

In order to safely carry out organ donation transplants during the outbreak of coronavirus disease 2019 (COVID-19), we have formulated strict procedures in place for organ donation and transplantation. We retrospectively analyzed our transplantation work from January 20 to May 5, 2020, to discuss whether organ transplantation can be carried out safely during the epidemic period. From January 20 to May 5, 43 cases of donation were carried out in our hospital, and the utilization rate of liver, kidney, heart, lung, and pancreas donations was more than 90%. Forty-one cases of liver transplantation and 84 cases of kidney transplantation were performed. No graft loss or recipient death occurred within one month after kidney transplantation, and one patient (2.4%) died after liver transplantation. There was no significant difference in the length of hospital stay compared with that during the same period in the previous three years. More importantly, COVID-19 infection did not occur among healthcare providers, donors, patients, or their accompanying families in our center. Under the premise of correct protection, it is safe and feasible to carry out organ transplantation during the epidemic period. Our experience during the outbreak might provide a clinical reference for countries facing COVID-19 worldwide.

Characterization of mRNA Expression and Endogenous RNA Profiles in Bladder Cancer Based on The Cancer Genome Atlas (TCGA) Database.

BACKGROUND Bladder cancer is a multifactorial disease with increasing incidence and mortality. Genetic alterations and altered expressions of mRNAs, long non-coding RNAs (lncRNAs), and miRNAs have been shown to play important roles in the tumorigenesis of bladder cancer. However, the functions of key RNAs and their regulatory network in bladder cancer are still to be elucidated. MATERIAL AND METHODS RNA profiles were downloaded from The Cancer Genome Atlas (TCGA) database. The differentially expressed mRNAs, lncRNAs, and miRNAs in bladder cancer were acquired through analyses of data from 414 bladder cancer tissues and 19 normal bladder tissues. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis was performed by using "DAVID6.8" and the R package "ClusterProfile". Protein-protein interaction and competing endogenous RNA (ceRNA) networks were constructed by using "STRING" database and Cytoscape 3.6.2. Based on the clinical data and Cox regression, a prognosis model was established, and survival analysis was performed. RESULTS A total of 1819 mRNAs, 659 lncRNAs, and 160 miRNAs were identified as significantly differentially expressed in bladder cancer of which 52 mRNAs, 58 lncRNAs, and 22 miRNAs were incorporated in the ceRNA network. CFL2 and TPM2 were found to be downregulated and showed significant correlation to each other in bladder cancer. HOXB5 and 6 lncRNAs (ADAMTS9-AS1, AC112721.1, LINC00460, AC110491.1, LINC00163, and HCG22) were strongly associated with high-grade, disease stages, and overall survival. CONCLUSIONS In this study, we have identified differentially expressed mRNAs, lncRNAs, and miRNAs in bladder cancer which were strongly associated with oncogenesis and prognosis. Further experimental studies are necessary to validate these results.

The First Case of Ischemia-Free Kidney Transplantation in Humans.

Background: Ischemia-reperfusion injury (IRI) has been considered an inevitable event in organ transplantation since the first successful kidney transplant was performed in 1954. To avoid IRI, we have established a novel procedure called ischemia-free organ transplantation. Here, we describe the first case of ischemia-free kidney transplantation (IFKT). Materials and Methods: The kidney graft was donated by a 19-year-old brain-dead donor. The recipient was a 47-year-old man with end-stage diabetic nephropathy. The graft was procured, preserved, and implanted without cessation of blood supply using normothermic machine perfusion. Results: The graft appearance, perfusion flow, and urine production suggested that the kidney was functioning well-during the whole procedure. The creatinine dropped rapidly to normal range within 3 days post-transplantation. The levels of serum renal injury markers were low post-transplantation. No rejection or vascular or infectious complications occurred. The patient had an uneventful recovery. Conclusion: This paper marks the first case of IFKT in humans. This innovation may offer a unique solution to optimizing transplant outcomes in kidney transplantation.

Knockdown of lncRNA SNHG7 inhibited cell proliferation and migration in bladder cancer through activating Wnt/ß-catenin pathway.

It is identified that long non-coding RNAs (lncRNAs) play important roles in tumorigenesis. LncRNA SNHG7 has been found to be an oncogene in varieties of tumors including bladder cancer. However, its potential regulatory mechanism in bladder cancer still remains unknown. In this study, we discovered that the expression levels of SNHG7 were significantly increased in bladder cancer tissues and cell lines. Patients with high expression level of SNHG7 suffered from poor prognosis. Additionally, knockdown of SNHG7 induced declined cell viability, proliferation as well as G0/G1 cell cycle arrest. Furthermore, we found that cell migratory ability was markedly reduced after silencing SNHG7. Next, we verified that knockdown of SNHG7 reduced the protein level of ß-catenin and thus decreased the level of its downstream targets including c-myc, cyclin D1 and E-cadherin, implying that SNHG7 might impact bladder cancer via Wnt/ß-catenin pathway. Subsequently, the rescue assays performed in SNHG7 silenced T24 cells by using activator of Wnt/ß-catenin signaling elucidated that re-activation of this pathway partly restored the inhibitory effects of SNHG7 suppression on biological behaviors of T24 cells. Collectively, SNHG7 elicited carcinogenic functions in bladder cancer partially via activating Wnt/ß-catenin signaling pathway, suggesting a potential target for the treatment and prognosis of bladder cancer.

Ex vivo liver resection and autotransplantation as alternative to allotransplantation for end-stage hepatic alveolar echinococcosis.

BACKGROUND & AIMS: Radical resection is the best treatment for patients with advanced hepatic alveolar echinococcosis (AE). Liver transplantation is considered for selected advanced cases; however, a shortage of organ donors and the risk of postoperative recurrence are major challenges. The aim of this study was to assess the clinical outcomes of ex vivo liver resection and autotransplantation for end-stage AE. METHODS: In this prospective study, 69 consecutive patients with end-stage hepatic AE were treated with ex vivo resection and liver autotransplantation between January 2010 and February 2017. The feasibility, safety and long-term clinical outcome of this technique were assessed. RESULTS: Ex vivo extended hepatectomy with autotransplantation was successful in all patients without intraoperative mortality. The median weight of the graft and AE lesion were 850 (370-1,600) g and 1,650 (375-5,000) g, respectively. The median duration of the operation and anhepatic phase were 15.9 (8-24) h and 360 (104-879) min, respectively. Six patients did not need any blood transfusion. Complications higher than IIIa according to Clavien classification were observed in 10 patients. The 30-day-mortality and overall mortality (>90 days) were 7.24% (5/69) and 11.5% (8/69), respectively. The mean hospital stay was 34.5 (12-128) days. Patients were followed-up systematically for a median of 22.5 months (14-89) without recurrence. CONCLUSION: This is the largest series assessing ex vivo liver resection and autotransplantation in end-stage hepatic AE. This technique could be an effective alternative to liver transplantation in patients with end-stage hepatic AE, with the advantage that it does not require an organ nor immunosuppressive agents. LAY SUMMARY: Ex vivo liver resection and autotransplantation were performed in a large series of patients with end-stage hepatic alveolar echinococcosis. The results showed that this surgical option was feasible, with acceptable postoperative mortality, but 100% disease-free survival in survivors. Careful patient selection, as well as precise assessment for size and quality of the remnant liver are key to successful surgery.

Anti-proliferative benefit of curcumol on human bladder cancer cells via inactivating EZH2 effector.

We investigated the molecular mechanism of curcumol-induced apoptosis in bladder cancer cells. The mitochondrial membrane potential was measured using JC-1 staining. ROS generation of bladder cancer cells was determined using the DCFH staining method. The apoptosis of bladder cancer cells was examined using the Annexin V-FITC and PI double-staining method. Enforced expression of EZH2 in bladder cancer cells was accomplished by transfecting an EZH2 expression plasmidinto EJ and T24 cells. siRNAs targeting EZH2 were used to inhibit endogenous expression of EZH2. Curcumol dose-dependently inhibited proliferation and colony formation and induced apoptosis in EJ and T24 bladder cancer cells. These effects correlated with decreased accumulation of EZH2. In addition, suppression of EZH2 enhanced the inhibitory effects of curcumol on cell growth and colony formation and increased curcumol-induced apoptosis. Conversely, enforced expression of EZH2 ameliorated the inhibitory effects of curcumol on cell growth and colony formation and decreased curcumol-induced apoptosis in EJ and T24 cells. We also found that suppression of EZH2 induced ROS generation and MMP loss in both EJ and T24 cells. Conversely, up-regulation of EZH2 suppressed ROS generation and MMP loss. Our data indicate that curcumol inhibits proliferation and induces apoptosis by targeting EZH2 and modulating the mitochondrial apoptosis pathway.

Long non-coding RNA cartilage injury-related promotes malignancy in bladder cancer.

Recent advances have highlighted the important roles of long non-coding RNAs (lncRNAs) in a number of biological processes, including oncogenesis. However, the function of lncRNA cartilage injury-related (lncRNA-CIR) in bladder cancer progression remains elusive. A novel function for lncRNA-CIR in bladder cancer was identified in the present study. Reverse transcription quantitative polymerase chain reaction, viability, invasion assay and in vivo implantation were used to evaluate the role of lncRNA-CIR. It was identified that the expression of lncRNA-CIR was frequently upregulated in 52 cancerous tissues and selected bladder cancer cell lines. Additionally, upregulating lncRNA-CIR was demonstrated to promote viability and invasion in T24 and SW780 cells, whereas siRNA-mediated lncRNA-CIR-knockdown consistently exhibited the opposite effects. High lncRNA-CIR levels also dictated poor overall survival among patients with bladder cancer. Furthermore, in vivo implantation experiments also supported a tumorigenic function for lncRNA-CIR, as decreasing lncRNA-CIR levels markedly attenuated Ki-67 staining and xenograft tumor growth. Overall, the present study identified a novel function of lncRNA-CIR and indicates that lncRNA-CIR may serve as a potential biomarker for bladder cancer treatment.

The first case of ischemia-free organ transplantation in humans: A proof of concept.

Ischemia and reperfusion injury (IRI) is an inevitable event in conventional organ transplant procedure and is associated with significant mortality and morbidity post-transplantation. We hypothesize that IRI is avoidable if the blood supply for the organ is not stopped, thus resulting in optimal transplant outcomes. Here we described the first case of a novel procedure called ischemia-free organ transplantation (IFOT) for patients with end-stage liver disease. The liver graft with severe macrovesicular steatosis was donated from a 25-year-old man. The recipient was a 51-year-old man with decompensated liver cirrhosis and hepatocellular carcinoma. The graft was procured, preserved, and implanted under continuous normothermic machine perfusion. The recipient did not suffer post-reperfusion syndrome or vasoplegia after revascularization of the allograft. The liver function test and histological study revealed minimal hepatocyte, biliary epithelium and vascular endothelium injury during preservation and post-transplantation. The inflammatory cytokine levels were much lower in IFOT than those in conventional procedure. Key pathways involved in IRI were not activated after allograft revascularization. No rejection, or vascular or biliary complications occurred. The patient was discharged on day 18 post-transplantation. This marks the first case of IFOT in humans, offering opportunities to optimize transplant outcomes and maximize donor organ utilization.

Utility of Fluorescence In Situ Hybridization (FISH) to Sub-Classify Low-Grade Urothelial Carcinoma for Prognostication.

BACKGROUND Fluorescence in situ hybridization (FISH) is used widely to detect cancer levels, but its value in urothelial carcinoma remains unclear. The aim of this study was to use FISH to examine the urine specimens of low-grade urothelial carcinoma (UC) patients to determine the possibility of sub-classifying the prognosis of UC. MATERIAL AND METHODS We diagnosed 107 patients with low-grade UC using a UroVysion kit to detect chromosomes 3, 7, 17, and P16 in the urine. An average 46.6-month follow-up completed in January 2016 combined with the clinical follow-up data were evaluated with Spearman's correlation analysis to analyze the aberration of chromosomes in relation to the prognostication. Univariate and multivariate analysis using the Mantel-Cox log-rank test for overall, cancer-specific, and disease-free survival were used to determine the prognostic significance of CSP7/CSP17 and CSP3/GLPp16. RESULTS In the 107 samples, 84 showed positive reaction in the FISH test. Furthermore, CSP7/CSP17 was found to be significantly related with age, tumor size, T stage, and tumor numbers, but not in CSP3/GLPp16. In addition, Kaplan-Meier analysis and Cox proportional hazards regression revealed a significant negative correlation between CSP7/CSP17 and survival, while CSP3/GLPp16 showed no significantly differences. CONCLUSIONS CSP7/CSP17 positivity on FISH test appears to play a critical role in low-grade UC and may be considered as a high-risk and prognosis factor.