CCNB1 is a novel prognostic biomarker and promotes proliferation, migration and invasion in Wilms tumor.

BACKGROUND: Wilms tumour (WT) is a mixed type of embryonal tumour that usually occurs in early childhood. However, our knowledge of the pathogenesis or progression mechanism of WT is inadequate, and there is a scarcity of beneficial therapeutic strategies. METHODS: High-throughput RNA sequencing was employed in this study to identify differentially expressed genes (DEGs) in clinical tumor samples and matching normal tissues. The STRING database was utilized to build a protein-protein interaction (PPI) network, and the Cytohubba method was used to identify the top 10 highly related HUB genes. Then, the key genes were further screened by univariate COX survival analysis. Subsequently, the XCELL algorithm was used to evaluate the tumour immune infiltration. RT-PCR, WB, and IF were used to verify the expression level of key genes in clinical tissues and tumour cell lines. Finally, the function of the key gene was further verified by loss-of-function experiments. RESULTS: We initially screened 1612 DEGs, of which 1030 were up-regulated and 582 were down-regulated. The GO and KEGG enrichment analysis suggested these genes were associated with 'cell cycle', 'DNA replication'. Subsequently, we identified 10 key HUB genes, among them CCNB1 was strongly related to WT patients' overall survival. Multiple survival analyses showed that CCNB1 was an independent indicator of WT prognosis. Thus, we constructed a nomogram of CCNB1 combined with other clinical indicators. Single gene GSEA and immune infiltration analysis revealed that CCNB1 was associated with the degree of infiltration or activation status of multiple immune cells. TIDE analysis indicated that this gene was correlated with multiple key immune checkpoint molecules and TIDE scores. Finally, we validated the differential expression level of CCNB1 in an external gene set, the pan-cancer, clinical samples, and cell lines. CCNB1 silencing significantly inhibited the proliferation, migration, and invasive capabilities of WIT-49 cells, also, promoted apoptosis, and in turn induced G2 phase cell cycle arrest in loss-of-function assays. CONCLUSION: Our study suggests that CCNB1 is closely related to WT progression and prognosis, and serves as a potential target.

Retrospective analysis of outcomes in patients with clear cell sarcoma of the kidney: A tertiary single-institution experience.

BACKGROUND: Clear cell sarcoma of the kidney (CCSK) is a rare and aggressive tumor. This study aims to describe the clinical characteristics and outcomes of CCSK patients in one of the largest pediatric medical centers in China. METHODS: We included all patients diagnosed with CCSK between January 2008 and March 2019 at the Children's Hospital of Chongqing Medical University, China. The patients' demographics, clinical presentation, and management were reviewed. Follow-up was continued until December 2019. RESULTS: In total, 41 CCSK patients (66% male) with a median age of 24 months (range 3-108 months) were identified. The stage distributions of stages I, II, III and IV were 42%, 34%, 24% and 0%, respectively. Preoperative chemotherapy was administered to 7/41 patients. All patients underwent radical nephrectomy and postoperative chemotherapy. The median number of lymph nodes sampled was 4 (range 1-12). Radiotherapy was applied in 8/41 patients. The 5-year event-free survival (EFS) and overall survival (OS) were 63.9% and 78.8%, respectively. Of the 41 patients, 11 patients experienced relapse at a median time of 19 months (range 5-72 months). The most common site of recurrence was the tumor bed (9/11). Young age was a significant adverse prognostic factor for EFS. CONCLUSIONS: The overall outcome of CCSK patients in our hospital is poorer than that in developed regions. More research is needed to clarify the underlying causes of poorer outcomes in young patients and improve outcomes. TYPE OF STUDY: Retrospective study. LEVEL OF EVIDENCE: LEVEL IV.

Trans-uretero-cystic external urethral stent for urinary diversion in pediatric laparoscopic pyeloplasty: A novel approach.

PURPOSE: We present a new approach for urine drainage in pediatric patients following laparoscopic pyeloplasty, the trans-uretero-cystic external urethral stent (TEUS). METHODS: We retrospectively identified 85 children who underwent laparoscopic pyeloplasty from July 2015 to June 2017. The included children were assigned to group A (double-J stent) or group B (TEUS). In group A, the double-J stent was removed by a cystoscopy under anesthesia after 1 month, while in group B, the external stent was removed after 5 to 7 days. We examined the durations of operation, hospital stay and the frequency of stent-related complications including urinary leakage, stent dislocation, stent occlusion, and urinary tract infection. RESULTS: The operation time was significantly longer for patients in group B than for those in group A. No significant difference was observed between the groups regarding stent-related complications. In group A, 4 patients need auxiliary stent re-insertion for the management of complications, 2 developed urinary tract infection, and 2 had stent occlusion. In group B, none needed auxiliary stent re-insertion for complications and avoided re-operation. CONCLUSIONS: In children, the outcome of external stent implantation was similar to that using double-J stent, and the use of the former approach may be beneficial for younger children.

Fluorogenic and chromogenic probe for rapid detection of a nerve agent simulant DCP.

A fluorogenic and visual probe was devised to detect diethyl chlorophosphate (DCP), a nerve agent simulant. The probe, N-(rhodamine B)-lactam-2-aminoethanol (RB-AE), undergoes oxazoline formation following phosphorylation in the presence of DCP, which gives rapid and clear fluorescence and color change in the assay solutions.

Pharmacological characterization of 3-azabicyclo[3,2,1] octane-1-yl-l-leucyl-d-tryptophanyl-d-4-Cl-phenylalanine: A novel ET(A) receptor-selective antagonist.

BACKGROUND AND OBJECTIVES: Pulmonary hypertension is a kind of disease associated with a very high rate of mortality. There are not many effective drugs for the treatment of pulmonary hypertension. Treatment with ET-1 receptor antagonists was proved to be effective in the treatment of pulmonary hypertension. Aiming at developing new endothelin A receptor (ET(A)) antagonist for treatment of pulmonary hypertension, 242 peptide compounds were synthesized by structural optimization of a selective ET(A) receptor antagonist BQ-123. Among these, -azabicyclo[3,2,1]octane-1-yl-l-Leucyl-d-tryptophanyl-d-4-Cl-phenylalanine, named ETP-508, was selected for further harmacological characterization. METHODS: Radioligand binding assay was performed to study the binding affinity of ETP-508 for ET(A) and ET(B) receptors. The biological activity of ETP-508 was evaluated in isolated rat aortic ring experiment and in systemic arterial pressure experiment. In addition, hypotensive effect of ETP-508 was investigated on hypoxia-induced pulmonary hypertension. RESULTS: ETP-508 binds to endothelin ET(A) receptor with >10,000-fold higher affinity than to endothelin B receptor in rat lung tissue preparation. ETP-508 inhibited endothelin-1 (ET-1)-induced contraction of isolated rat aortic ring and shifted the cumulative concentration-contraction response curve to ET-1 to right with no change in the maximal response. In vivo, ETP-508 inhibited the increased effect of ET-1 on mean systemic arterial pressure. Pre-treatment with ETP-508 by intravenous infusion significantly inhibited chronic hypoxia-induced pulmonary hypertension and right ventricular hypertrophy. ETP-508 also significantly inhibited the increase in lung ET-1 expression level, hemoglobin, red-cell count and red-cell hematocrit as induced by hypoxia. Furthermore, ETP-508 partially reversed pre-established pulmonary hypertension and right ventricle hypertrophy by chronic hypoxia. CONCLUSION: These results indicated that ETP-508 is a novel highly selective ET(A) receptor antagonist and may have a great potential to be developed as a drug of anti-pulmonary hypertension.