A novel risk signature that combines 10 long noncoding RNAs to predict neuroblastoma prognosis.

Neuroblastoma (NBL) is the most frequently encountered extracranial solid neoplasm and impacts significantly on the survival of patients, especially in cases of advanced tumor stage or relapse. A long noncoding RNA (lncRNA) signature to predict the survival of patients with NBL is proposed in this paper. Differentially expressed lncRNA (DElncRNA) was selected using the Limma plus Voom package in R based on the RNA-sequencing data downloaded from the Therapeutically Applicable Research To Generate Effective Treatments database and Genotype-Tissue Expression database. Univariate cox regression analysis, least absolute shrinkage and selection operator regression analysis, and multivariate cox regression analysis were conducted to identify candidate DElncRNAs for the risk signature. Consequently, 10 DElncRNAs were designated as candidate DElncRNAs for the risk signature. Time-dependent receiver operating characteristic curves and Kapan-Meier survival curves confirmed the efficacy of the risk signature in predicting the survival of patients with NBL (area under the curve = 0.941; p ≤ .001). One of the DElncRNA constituent subparts (LINC01010) was significantly associated with the survival outcome of patients with NBL in GSE62564 (p = .004). Thus, a risk signature comprising 10 DElncRNAs was identified as effective for individual risk stratification and the survival prediction outcomes of patients with NBL.

RNA-Sequencing, Connectivity Mapping, and Molecular Docking to Investigate Ligand-Protein Binding for Potential Drug Candidates for the Treatment of Wilms Tumor.

BACKGROUND Wilms tumor, or nephroblastoma, is a malignant pediatric embryonal renal tumor that has a poor prognosis. This study aimed to use bioinformatics data, RNA-sequencing, connectivity mapping, molecular docking, and ligand-protein binding to identify potential targets for drug therapy in Wilms tumor. MATERIAL AND METHODS Wilms tumor and non-tumor samples were obtained from high throughput gene expression databases, and differentially expressed genes (DEGs) were analyzed using the voom method in the limma package. The overlapping DEGs were obtained from the intersecting drug target genes using the Connectivity Map (CMap) database, and systemsDock was used for molecular docking. Gene databases were searched for gene expression profiles for complementary analysis, analysis of clinical significance, and prognosis analysis to refine the study. RESULTS From 177 cases of Wilms tumor, there were 648 upregulated genes and 342 down-regulated genes. Gene Ontology (GO) enrichment analysis showed that the identified DEGs that affected the cell cycle. After obtaining 21 candidate drugs, there were seven overlapping genes with 75 drug target genes and DEGs. Molecular docking results showed that relatively high scores were obtained when retinoic acid and the cyclin-dependent kinase inhibitor, alsterpaullone, were docked to the overlapping genes. There were significant standardized mean differences for three overlapping genes, CDK2, MAP4K4, and CRABP2. However, four upregulated overlapping genes, CDK2, MAP4K4, CRABP2, and SIRT1 had no prognostic significance. CONCLUSIONS RNA-sequencing, connectivity mapping, and molecular docking to investigate ligand-protein binding identified retinoic acid and alsterpaullone as potential drug candidates for the treatment of Wilms tumor.

Relationship between apolipoprotein E gene polymorphism with triglyceride level in patients with renal diseases.

Apolipoprotein E (apoE), one of the major plasma lipoproteins, plays a major role in the transport and metabolism of lipids by acting as a ligand. apoE gene contains three potential alleles: ϵ2, ϵ3 and ϵ4, forming six genotypes: E2E2, E2E3, E2E4, E3E3, E3E3 and E4E4. Association between apoE gene polymorphism and triglyceride (TG) is still controversial. There was not any meta-analysis to explore the association of apoE gene polymorphism with triglyceride level, and this meta-analysis was performed to evaluate the association between apoE gene polymorphism and triglyceride in patients with renal diseases. A predefined literature search and selection of eligible relevant studies were performed to collect data from electronic databases. Twenty-four articles were identified for the analysis of association between apoE gene polymorphism and triglyceride level. Subjects with E2E3 or E3E4 had a higher TG than those with E3E3. Subjects with ϵ4 had a higher TG than those with ϵ3. Subjects with ϵ2 had a slightly higher TG than those with ϵ3, although there was no statistical difference. Interestingly, subjects with ϵ4 had a much higher TG than those with ϵ2. In conclusion, E2E3, E3E4 or ϵ4 was associated with higher level of TG. However, more studies should be performed in the future.

[Modified Mathieu urethroplasty for failed hypospadias repair].

OBJECTIVE: To review the indications, techniques and complications of reoperation for failed hypospadias repair using modified Mathieu urethroplasty. METHODS: Using modified Mathieu urethroplasty, we treated 24 hypospadias patients aged 3-12 (mean 4.5) years for whom the first (n = 20) or the second hypospadias repair (n = 4) had failed, including 13 cases of large coronary sulcus urethrocutaneous fistula, 5 cases of urethral meatus retraction and 6 cases of anterior urethra dehiscence. The modified procedure involved median longitudinal incision of the urethral posterior wall, dorsal tunica albuginea plication under the vascular and nerve bundle, and double dartos flap protection of the neourethra. RESULTS: Of the 24 patients, 19 (79.2%) were successfully treated by the first operation, which achieved desirable straightness, good cosmetic appearance and normal urethral meatus of the penis, without postoperative complications. Small urethrocutaneous fistula developed in 4 cases, of which 3 were cured by fistula repair and 1 self-healed. Urethral meatus stenosis occurred in 1 case, which was restored by meatal dilation. Urethrocele and urethrostenosis were not found in any of the cases. Two cases received urethroscopy postoperatively, which revealed no hypertrophic cicatrix at the site of median longitudinal incision in the urethral posterior wall. CONCLUSION: Modified Mathieu urethroplasty can be applied to hypospadias reoperation, particularly in such cases as large coronary sulcus urethrocutaneous fistula, urethral meatus retraction and anterior urethra dehiscence. The modified procedure includes median longitudinal incision of the urethral posterior wall, dorsal tunica albuginea plication under the vascular and nerve bundle, and double dartos flap protection of the neourethra.

The Expression and Potential Role of Tubulin Alpha 1b in Wilms' Tumor.

We explored the difference in expression of tubulin alpha 1b (TUBA1B) between Wilms' tumor (WT) and normal tissues (NT) from in-house patients and databases, to determine TUBA1B expression in WT and the predictive pathways of coexpressed genes. In-house RNA-sequencing data were performed with WT and NT from three patients from our institute. Other four RNA-sequencing and microarray data were also downloaded from multiple public databases. The TUBA1B expression between WT and NT was analyzed by Student's t-test and meta-analysis. The correlation between the expression of TUBA1B and other genes in each study was analyzed. Genes with p < 0.05 and r > 0.5 were considered as the coexpressing genes of TUBA1B. Overlapping the coexpressed genes of the five studies, including three in-house patients (3 WT vs. 3 NT), GTEx-TARGET (126 WT vs. 51 NT), GSE2172 (18 WT vs. 3 NT), GSE11024 (27 WT vs. 12 NT), and GSE73209 (32 WT vs. 6 NT), were performed with limma and VennDiagram packages in R software. The website of WEB-based GEne SeT AnaLysis toolkit were used to analyze the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotations for the overlapped genes. The results showed that the relative expression of TUBA1B in WT tissues from in-house three patients was 280.0086, 141.7589, and 303.8292 and that in NT was 16.5836, 104.8141, and 12.79 (3 WT vs. 3 NT, p = 0.0285, ROC = 100%, SMD = 2.74). Student's t-test and meta-analysis in all studies revealed that the expression of TUBA1B was upregulated in WT tissues compared to that in NT (p < 0.05, SMD = 2.89, sROC = 0.98). Finally, the research identified the expression of TUBA1B in WT tissues was significantly upregulated than that in NT. The coexpressed genes of TUBA1B were enriched in the pathway of DNA replication, mismatch repair, cell cycle, pathogenic Escherichia coli infection, and spliceosome.

Nomogram for predicting overall survival in children with neuroblastoma based on SEER database.

PURPOSE: This study was performed to establish and validate a nomogram for predicting the overall survival in children with neuroblastoma. METHODS: The latest clinical data of neuroblastoma in Surveillance, Epidemiology, and End Results (SEER) database was extracted from 2000 to 2016. The cases included were randomly divided into training and validation cohorts. The survival curves were drawn with a Kaplan-Meier estimator to investigate the influences of certain single factors on overall survival. Also, least absolute shrinkage and selection operator regression was applied to further select the prognostic variables for neuroblastoma. Additionally, receiver operating characteristic (ROC) curves and calibration curves were used to evaluate the accuracy of the nomogram. RESULTS: In total, 1,262 patients were collected and 8 independent prognostic factors were achieved, including patients' age, sex, race, tumor grade, radiotherapy, chemotherapy, tumor site, and tumor size. Then we constructed a nomogram by using the data of the training cohort with 886 cases. Subsequently, the nomogram was validated internally and externally with 886 and 376 cases, respectively. The internal validation revealed that the area under the curves (AUC) of ROC curves of 1-, 3-, and 5-year overall survival were 0.69, 0.78, and 0.81, respectively. Accordingly, the external validation also showed that the AUC of 1-, 3-, and 5-year overall survival were all ≥0.69. Both methods of validation demonstrated that the predictive calibration curves were consistent with standard curves. CONCLUSION: The nomogram possess the potential to be a new tool in predicting the survival rate of neuroblastoma patients.

[Treatment and outcome of 14 children with hepatoblastoma].

OBJECTIVE: To assess the outcome of childhood hepatoblastoma after a combination therapy of resection and chemotherapy. METHODS: The clinical data of 14 children with hepatoblastoma was retrospectively reviewed. Their long-term survival was followed-up. RESULTS: Twelve cases received surgery and planned chemotherapy. The follow-up duration averaged 18 months (range 1.5-74 months). Nine survived free of events, 1 died, 1 survived with multiple lung metastases, and 1 with increased alpha-fetoprotein (AFP) content but without residual tumor. CONCLUSIONS: Surgery assisted with chemotherapy can improve the outcome of hepatoblastoma.

Primitive neuroectodermal tumors of the abdominal wall and vulva in children: Report of two cases and review of the literature.

BACKGROUND: Primitive neuroectodermal tumors are rare, highly malignant small round cell tumors belonging to the Ewing sarcoma family. The purpose of this article is to present clinical manifestation, histology, treatment, and prognosis of two primitive neuroectodermal tumors (PNETs) in extremely rare anatomic locations, the abdominal wall and vulva. CASE SUMMARY: Case 1 was a 66-month-old girl with lesions on the abdominal wall; tumor size was about 3.4 cm × 6.1 cm × 2 cm. The patient underwent radical resection of the tumor. After the operation, an alternating vincristine, doxorubicin, and cyclophosphamide/ifosfamide and etoposide (IE) regimen was given for eight cycles, and the patient survived for 66 mo without progression. Case 2 was a 40-month-old girl, with a vulvar lesion; tumor size was about 3.3 cm × 5 cm × 2.5 cm. The tumor was partially resected by surgery. The family left treatment after two cycles of vincristine, pirarubicin, and cyclophosphamide/IE chemotherapy, and the patient died at home six months after surgery. CONCLUSION: PNET is a rare, fast-growing, highly malignant tumor that requires histologic and molecular analyses for exact diagnosis, and multimodal treatment is required to achieve a good prognosis.

Effects of modified penoplasty for concealed penis in children.

PURPOSE: To evaluate the effect of modified penoplasty in the management of concealed penis. METHODS: We retrospectively reviewed 96 consecutive patients with concealed penis, which had been surgically corrected between July 2013 and July 2015. All patients underwent modified Shiraki phalloplasty. All patients were scheduled for regular follow-up at 1, 3, and 6 months after the surgery. Data on the patients' age, operative time, postoperative complications, and parents' satisfaction grade were collected and analyzed. RESULTS: The mean follow-up period was 17.4 months (range 7-31 months). The mean operative time was 63.2 ± 8.7 min. The mean perpendicular penile length was 1.89 ± 0.77 cm preoperatively and 4.42 ± 0.87 cm postoperatively, with an improved mean length of 2.5 ± 0.68 cm in the flaccid state postoperatively (p < 0.05). The patients' satisfaction grades after the surgery were improved significantly (p < 0.05). Fifty-two patients had penile lymphedema postoperatively; however, it disappeared spontaneously within 3 months. Additionally, postoperative wound infection occurred in two patients. There were no complications such as flap necrosis, penile shaft contracture, voiding difficulty, and erection difficulties. CONCLUSION: The modified Shiraki phalloplasty for concealed penis can achieve maximum utilization of prepuce to assure coverage of the exposed penile shaft. It has fewer complications, achieving marked asthetics, and functional improvement. It is a relatively ideal means for treating concealed penis.