N6-methyladenosine modification of circMARK2 enhances cytoplasmic export and stabilizes LIN28B, contributing to the progression of Wilms tumor.

BACKGROUND: The potential involvement of circular RNAs (circRNAs) and N6-methyladenosine (m6A) modification in the progression of Wilms tumor (WT) has not been fully elucidated. This study investigates the regulatory mechanisms and clinical significance of m6A-modified circMARK2 and its role in WT progression. METHODS: We identified dysregulated circRNAs through deep sequencing and validated their expression by qRT-PCR in WT tissues. The biological functions of circMARK2 were assessed using clone formation, transwell migration, and orthotopic animal models. To dissect the underlying mechanisms, we employed RNA immunoprecipitation, RNA pull-down, dual-luciferase reporter assays, Western blotting, and immunofluorescence and immunohistochemical staining. RESULTS: CircMARK2, upregulated in WT tissues, was found to be m6A-modified and promoted cytoplasmic export. It facilitated WT progression by stabilizing LIN28B mRNA through the circMARK2/IGF2BP2 interaction. In vitro and in vivo studies demonstrated that circMARK2 enhances the malignant behavior of WT cells. Clinically, higher circMARK2 levels in tumor tissues of WT patients were linked to increased tumor aggressiveness and reduced survival rates. CONCLUSIONS: Our study provides the first comprehensive evidence that m6A-modified circMARK2 contributes to WT progression by enhancing LIN28B mRNA stability, promoting cellular aggressiveness. CircMARK2 emerges as a potential biomarker for prognosis and a promising target for therapeutic intervention in WT, underscoring the clinical relevance of m6A modification in pediatric renal cancer.

LMO family gene polymorphisms and Wilms tumor susceptibility in Chinese children: a five-center case-control study.

BACKGROUND: Wilms tumor is the most prevalent embryonal kidney malignancy in children worldwide. Previous genome-wide association study (GWAS) identified that LIM domain only 1 (LMO1) gene polymorphisms affected the susceptibility to develop certain tumor types. Apart from LMO1, the LMO gene family members also include LMO2-4, each of which has oncogenic potential. METHODS: We conducted this five-center case‒control study to assess the correlations between single nucleotide polymorphisms in LMO family genes and Wilms tumor susceptibility. Odds ratios and 95% confidence intervals were calculated to evaluate the strength of the association. RESULTS: We found LMO1 rs2168101 G > T and rs11603024 C > T as well as LMO2 rs7933499 G > A were significantly associated with Wilms tumor risk. Stratified analysis demonstrated a protective role of rs2168101 GT/TT genotypes against Wilms tumor in the subgroups of age ≤ 18 months, males and clinical stages I/II compared to the rs2168101 GG genotype. Nevertheless, carriers with the rs11603024 TT genotype were more likely to have an increased risk of Wilms tumor than those with rs11603024 CC/CT genotypes in age > 18 months. And the rs11603024 was identified as a protective polymorphism for reducing the risk of Wilms tumor in the sex- and gender- subgroup. Likewise, carriers with the rs7933499 GA/AA genotypes were at significantly elevated risk of Wilms tumor in age ≤ 18 months and clinical stages I/II. CONCLUSION: Overall, our study identified the importance of LMO family gene polymorphisms on Wilms tumor susceptibility in Chinese children. Further investigations are needed to validate our conclusions.

PABPC1L Induces IDO1 to Promote Tryptophan Metabolism and Immune Suppression in Renal Cell Carcinoma.

The tumor microenvironment (TME) in renal cell carcinomas (RCC) is marked by substantial immunosuppression and immune resistance despite having extensive T-cell infiltration. Elucidation of the mechanisms underlying immune evasion could help identify therapeutic strategies to boost the efficacy of immune checkpoint blockade (ICB) in RCC. This study uncovered a mechanism wherein the polyadenylate-binding protein PABPC1L modulates indoleamine 2,3-dioxygenase 1 (IDO1), a prospective target for immunotherapy. PABPC1L was markedly upregulated in RCC, and high PABPC1L expression correlated with unfavorable prognosis and resistance to ICB. PABPC1L bolstered tryptophan metabolism by upregulating IDO1, inducing T-cell dysfunction and Treg infiltration. PABPC1L enhanced the stability of JAK2 mRNA, leading to increased JAK2-STAT1 signaling that induced IDO1 expression. Additionally, PABPC1L-induced activation of the JAK2-STAT1 axis created a positive feedback loop to promote PABPC1L transcription. Conversely, loss of PABPC1L diminished IDO1 expression, mitigated cytotoxic T-cell suppression, and enhanced responsiveness to anti-PD-1 therapy in patient-derived xenograft models. These findings reveal the crucial role of PABPC1L in facilitating immune evasion in RCC and indicate that inhibiting PABPC1L could be a potential immunotherapeutic approach in combination with ICB to improve patient outcomes. SIGNIFICANCE: PABPC1L functions as a key factor in renal cell carcinoma immune evasion, enhancing IDO1 and impeding T-cell function, and represents a potential target to enhance the efficacy of immune checkpoint blockade therapy.

WDR4 gene polymorphisms and Wilms tumor susceptibility in Chinese children: A five-center case-control study.

Wilms tumor is the most common embryonal renal malignancy in children. WDR4 is an indispensable noncatalytic subunit of the RNA N7-methylguanosine (m7G) methyltransferase complex and plays an essential role in tumorigenesis. However, the relationship between polymorphisms in the WDR4 gene and susceptibility to Wilms tumor remains to be fully investigated. We performed a large case-control study involving 414 patients and 1199 cancer-free controls to investigate whether single nucleotide polymorphisms (SNPs) in the WDR4 gene are associated with Wilms tumor susceptibility. WDR4 gene polymorphisms (rs2156315 C > T, rs2156316 C > G, rs6586250 C > T, rs15736 G > A, and rs2248490 C > G) were genotyped using the TaqMan assay. In addition, unconditioned logistic regression analysis was performed, odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association between WDR4 gene SNPs and Wilms tumor susceptibility as well as the strength of the associations. We found that only the rs6586250 C>T polymorphism was significantly associated with an increased risk of Wilms tumor (adjusted OR=2.99, 95% CI = 1.28-6.97, P = 0.011 for the rs6586250 TT genotype; adjusted OR=3.08, 95% CI = 1.33-7.17, P = 0.009 for the rs6586250 CC/CT genotype). Furthermore, the stratification analysis revealed that patients with the rs6586250 TT genotype and carriers with 1-5 risk genotypes exhibited statistically significant associations with increased Wilms tumor risk in specific subgroups. However, the rs2156315 CT/TT genotype was identified as having a protective effect against Wilms tumor in the age >18 months subgroup compared with the rs2156315 CC genotype. In brief, our study demonstrated that the rs6586250 C > T polymorphism of the WDR4 gene was significantly associated with Wilms tumor. This finding may contribute to the understanding of the genetic mechanism of Wilms tumor.

Clinical characteristics, socioeconomic factors and COVID-19 were associated with delayed surgery in children with hypospadias: a retrospective study of 4439 cases in a single center.

BACKGROUND: Hypospadias is one of the most common congenital diseases of the genitourinary system in children. The European Association of Urology (EAU) Guidelines recommend that children undergoing hypospadias surgery should be between 6 and 18 months. In China, where many children have hypospadias, it remains unknown whether clinical characteristics, socioeconomic factors and COVID-19 were associated with delayed surgery in children with hypospadias. METHODS: We retrospectively analyzed children with hypospadias who underwent primary surgery at the Department of Pediatric Urology in Guangzhou Women and Children's Medical Center between January 2010 and October 2021. Patients who had two-stage surgery or a second round of surgery due to complications were excluded to eliminate data duplication. The clinical characteristics and demographic information were collected. We defined delayed surgery as primary surgery performed after 18 months following the EAU Guidelines. RESULTS: A total of 4439 children diagnosed with hypospadias were included in the study. The median age (29.1 ± 16.7 months) of surgery for hypospadias in our study was much higher than the recommended age reported in the EAU guidelines, and 76.6% of the children underwent surgery after the age of 18 months. Children without comorbidities including cryptorchidism (odds ratio [OR] = 1.562; 95% confidence interval [CI] 1.199-2.034; p = 0.001), prostatic cyst (OR = 2.613; 95% CI 1.579-4.324; p < 0.001), penile hypoplasia (OR = 1.778; 95% CI 1.225-2.580; p = 0.002), inguinal hernia (OR = 2.070; 95% CI 1.394-3.075; p < 0.001), and penoscrotal transposition (OR = 4.125; 95% CI 1.250-13.619; p = 0.020) were more likely to receive delayed surgery. Living in a low economic area (OR = 1.731; 95% CI 1.068-2.806; p = 0.026) or not close to a main medical center (OR = 1.580; 95% CI 1.370-1.824; p < 0.001) was highly associated with delayed surgery. The proportion of children undergoing delayed surgery and the median age of surgery during the COVID-19 pandemic were significantly higher than those before the COVID-19 pandemic (p = 0.004 and < 0.001, respectively). CONCLUSIONS: Most children with hypospadias received delayed surgery (surgical age > 18 months). Comorbidities, living in a low economic area, too far from a main medical center and the COVID-19 pandemic were highly associated with delayed surgery. It is vital to improve the public awareness of hypospadias and strengthen the re-education of primary community doctors to reduce delayed surgery.

The inhibition of CFTR in the descended testis of SD rats with unilateral cryptorchidism induced by di-(2-ethylhexyl) phthalate (DEHP).

Di-(2-ethylhexyl) phthalate (DEHP) is a kind of environmental endocrine disruptors (EEDs), which has been confirmed to cause serious consequences, such as cryptorchidism. Patients with unilateral cryptorchidism still had oligospermia or infertility even if they received orchidopexy before puberty. Testicular dysgenesis syndrome (TDS) attributes this kind of problems to the abnormal testicular development during the embryonic period, and considers that the environmental exposure factors during pregnancy play a major role. Therefore, for unilateral cryptorchidism, even if one testicle has dropped to scrotum, it may be exposed to these substances and cause damage. Cystic fibrosis transmembrane conduction regulator (CFTR) is very important for the maturation of male reproductive system. Previously, cryptorchidism was thought to cause abnormal expression of heat sensitive protein CFTR in testis, but the expression of CFTR in healthy side (descended side) testis was not clear. In this study, we established SD rats with unilateral cryptorchidism by exposure to DEHP (500 mg/kg/day) during pregnancy, and detected the expression of CFTR and downstream signal NF-κB/COX-2/PGE2 in bilateral testis. Finally, we found that the expression of CFTR and downstream signal NF-κB/COX-2/PGE2 in the undescended testis was significantly abnormal, but the expression of them in the descended testis was also abnormal to some extent. Therefore, we speculate that in addition to high temperature will affect the expression of CFTR, there may be other factors that cause abnormal expression of CFTR induced by DEHP, and lead to abnormal male reproductive function eventually, but the specific mechanism needs to be further studied.

Causal relationship between physical activity, leisure sedentary behaviors and COVID-19 risk: a Mendelian randomization study.

BACKGROUND: The 2019 coronavirus disease pandemic (COVID-19) poses an enormous threat to public health worldwide, and the ensuing management of social isolation has greatly decreased opportunities for physical activity (PA) and increased opportunities for leisure sedentary behaviors (LSB). Given that both PA and LSB have been established as major influencing factors for obesity, diabetes and cardiometabolic syndrome, whether PA/LSB in turn affects the susceptibility to COVID-19 by disrupting metabolic homeostasis remains to be explored. In this study, we aimed to systematically evaluate the causal relationship between PA/LSB and COVID-19 susceptibility, hospitalization and severity using a Mendelian randomization study. METHODS: Data were obtained from a large-scale PA dataset (N = 377,000), LSB dataset (N = 422,218) and COVID-19 Host Genetics Initiative (N = 2,586,691). The causal effects were estimated with inverse variance weighted, MR-Egger, weighted median and MR-PRESSO. Sensitivity analyses were implemented with Cochran's Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis and the funnel plot. Risk factor analyses were further conducted to investigate the potential mediators. RESULTS: Genetically predicted accelerometer-assessed PA decreased the risk for COVID-19 hospitalization (OR = 0.93, 95% CI 0.88-0.97; P = 0.002), while leisure television watching significantly increased the risk of COVID-19 hospitalization (OR = 1.55, 95% CI 1.29-1.88; P = 4.68 × 10-6) and disease severity (OR = 1.85, 95% CI 1.33-2.56; P = 0.0002) after Bonferroni correction. No causal effects of self-reported moderate to vigorous physical activity (MVPA), accelerometer fraction of accelerations > 425 milligravities, computer use or driving on COVID-19 progression were observed. Risk factor analyses indicated that the above causal associations might be mediated by several metabolic risk factors, including smoking, high body mass index, elevated serum triglyceride levels, insulin resistance and the occurrence of type 2 diabetes. CONCLUSION: Our findings supported a causal effect of accelerometer-assessed PA on the reduced risk of COVID-19 hospitalization as well as television watching on the increased risk of COVID-19 hospitalization and severity, which was potentially mediated by smoking, obesity and type 2 diabetes-related phenotypes. Particular attention should be given to reducing leisure sedentary behaviors and encouraging proper exercise during isolation and quarantine for COVID-19.

Aggregation caused quenching to aggregation induced emission transformation: a precise tuning based on BN-doped polycyclic aromatic hydrocarbons toward subcellular organelle specific imaging.

Polycyclic aromatic hydrocarbons (PAHs) with boron-nitrogen (BN) moieties have attracted tremendous interest due to their intriguing electronic and optoelectronic properties. However, most of the BN-fused π-systems reported to date are difficult to modify and exhibit traditional aggregation-caused quenching (ACQ) characteristics. This phenomenon greatly limits their scope of application. Thus, continuing efforts to seek novel, structurally distinct and functionally diverse structures are highly desirable. Herein, we proposed a one-stone-two-birds strategy including simultaneous exploration of reactivity and tuning of the optical and electronic properties for BN-containing π-skeletons through flexible regioselective functionalization engineering. In this way, three novel functionalized BN luminogens (DPA-BN-BFT, MeO-DPA-BN-BFT and DMA-DPA-BN-BFT) with similar structures were obtained. Intriguingly, DPA-BN-BFT, MeO-DPA-BN-BFT and DMA-DPA-BN-BFT exhibit completely different emission behaviors. Fluorogens DPA-BN-BFT and MeO-DPA-BN-BFT exhibit a typical ACQ effect; in sharp contrast, DMA-DPA-BN-BFT possesses a prominent aggregation induced emission (AIE) effect. To the best of our knowledge, this is the first report to integrate ACQ and AIE properties into one BN aromatic backbone with subtle modified structures. Comprehensive analysis of the crystal structure and theoretical calculations reveal that relatively large twisting angles, multiple intermolecular interactions and tight crystal packing modes endow DMA-DPA-BN-BFT with strong AIE behavior. More importantly, cell imaging demonstrated that luminescent materials DPA-BN-BFT and DMA-DPA-BN-BFT can highly selectively and sensitively detect lipid droplets (LDs) in living MCF-7 cells. Overall, this work provides a new viewpoint of the rational design and synthesis of advanced BN-polycyclic aromatics with AIE features and triggers the discovery of new functions and properties of azaborine chemistry.

Causal relationship between 14 site-specific cancers and venous thromboembolism.

Background: It has been observed that cancer and venous thromboembolism (VTE) are associated, but anticancer therapy may violate the causality. Therefore, this study aimed to elucidate the causal relationship of various cancers to VTE using Mendelian randomization (MR). Methods: Three MR methods were used to estimate causal effects: Inverse variance weighted (IVW), MR-Egger and weighted median. Sensitivity analyses included Cochran's Q-test, MR-Egger intercept test and MR-PRESSO. Gene ontology enrichment analysis was performed to elucidate the underlying mechanisms of VTE development in cancer patients. Results: The primary IVW approach showed that non-Hodgkin's lymphoma (NHL) might increase the risk of VTE (odds ratio [OR]: 1.20, 95% confidence interval [95% CI]: 1.00-1.44, p = 0.045), while melanoma possibly reduced the risk of VTE (OR: 0.89, 95% CI: 0.82-0.97, p = 0.006), although there was no significance after adjustment for multiple testing. No association was observed between VTE risk and other site-specific cancers. Gene ontology enrichment analysis revealed that vitamin D played an important role in the development of VTE in cancer patients. Conclusions: Our findings suggested that genetically predicted NHL was associated with higher VTE risk, whereas melanoma had lower VTE risk compared with other site-specific cancers. Moreover, this study suggested that anticancer therapy and increased extensive examination might play a more important role in VTE development than the nature of cancer.

Association between LIN28B gene polymorphisms and Wilms' tumor susceptibility.

Aim: To survey the association between LIN28B gene polymorphisms and the increased risk of Wilms' tumor (WT). Methods: Five LIN28B polymorphisms (rs314276 C>A, rs221634 A>T, rs221635 T>C, the rs4145418 A>C and rs9404590 T>G) were genotyped in 355 WT patients and 1070 healthy controls to assess the association. Result: The rs314276 CA/AA genotype was a protective factor against WT (corrected odds ratio [OR]: 0.71; p = 0.006). Individuals older than 18 months (corrected OR: 0.60; p = 0.001), males (corrected OR: 0.65; p = 0.011) and in clinical stage I + II patients (corrected OR: 0.60; p = 0.0008) with this genotype were less susceptible to WT. Conclusion: The rs314276 CA/AA genotype may protect against WT.

METTL14 gene polymorphisms decrease Wilms tumor susceptibility in Chinese children.

BACKGROUND: Wilms tumor is a highly heritable malignancy. Aberrant METTL14, a critical component of N6-methyladenosine (m6A) methyltransferase, is involved in carcinogenesis. The association between genetic variants in the METTL14 gene and Wilms tumor susceptibility remains to be fully elucidated. We aimed to assess whether variants within this gene are implicated in Wilms tumor susceptibility. METHODS: A total of 403 patients and 1198 controls were analyzed. METTL14 genotypes were assessed by TaqMan genotyping assay. RESULT: Among the five SNPs analyzed, rs1064034 T > A and rs298982 G > A exhibited a significant association with decreased susceptibility to Wilms tumor. Moreover, the joint analysis revealed that the combination of five protective genotypes exerted significantly more protective effects against Wilms tumor than 0-4 protective genotypes with an OR of 0.69. The stratified analysis further identified the protective effect of rs1064034 T > A, rs298982 G > A, and combined five protective genotypes in specific subgroups. The above significant associations were further validated by haplotype analysis and false-positive report probability analysis. Preliminary mechanism exploration indicated that rs1064034 T > A and rs298982 G > A are correlated with the expression and splicing event of their surrounding genes. CONCLUSIONS: Collectively, our results suggest that METTL14 gene SNPs may be genetic modifiers for the development of Wilms tumor.

[Mean microvessel density of the prepuce and its relationship with the severity of hypospadias and early postoperative complications].

OBJECTIVE: To investigate the mean preputial microvessel density (mMVD) and features of hypospadias and their relationship with the severity and early postoperative complications of the disease. METHODS: Sixty children with hypospadias and another 14 age-matching ones with phimosis (the control group) underwent penile curvature correction, Snodgrass procedure or staged surgery, the excessive dorsal foreskin trimmed and retained. We determined the mMVD in the prepuce tissue of the patients by immunohistochemistry, and followed up those treated by Snodgrass procedure. RESULTS: The mMVD was significantly lower in the patients with severe hypospadias than in those with mild hypospadias and the controls (15.51 ± 3.53 vs 19.27 ± 4.42 and 22.09 ± 6.15, P < 0.05), with a median of 21.8 in the control group. The incidence of postoperative complications was obviously lower in the high mMVD (≥ 21.8) than in the low mMVD (< 21.8) group. CONCLUSIONS: The preputial mMVD is significantly lower in patients with severe hypospadias than in normal children, decreasing in a severity-dependent manner. The lower the preputial mMVD, the higher the incidence rate of postoperative complications. The preputial mMVD of 21.8 can be used as a reference index for evaluating the prognosis of surgery clinically. ?

CircCDYL Acts as a Tumor Suppressor in Wilms' Tumor by Targeting miR-145-5p.

Circular RNAs (circRNA) have been reported to exert evident functions in many human carcinomas. However, the possible mechanisms concerning the circRNA in various tumors are still elusive. In this research, we analyzed the expression profile and biological functions of circular RNA CDYL (circCDYL, circBase ID: hsa_circ_0008285) in Wilms' tumor. Here, miRNA and gene expression were examined by real-time PCR in Wilms' tumor tissues and cell lines. The functions of circCDYL and its potential targets to influence cell proliferation, migration, and invasion in Wilms' tumor cells were determined by biological functional experiments in vitro and in vivo. We predicted and analyzed potential miRNA targets through online bioinformatic tools. To validate the interactions between circCDYL and its targets, we performed RNA fluorescence in situ hybridization, biotin-coupled miRNA capture assay, and biotin-coupled probe pull-down assay. Tight junction protein l (TJP1) was proved to be the target gene of the predicted miRNA by dual-luciferase reporter assay. The expression level of TJP1 in Wilms' tumor cells was identified via Western blot. We showed that circCDYL was downregulated in WT tissue compared with adjacent non-tumor tissue. Upregulation of circCDYL could reduce cell proliferation, migration, and invasion. Mechanically, circCDYL, functioning as a miRNA sponge, decreased the expression level of miR-145-5p and TJP1 3'UTR was validated as the target of miR-145-5p, facilitating the circCDYL/miR-145-5p/TJP1 axis. In conclusion, our study suggested circCDYL as a novel biomarker and therapeutic target for WT treatment.

HA-coated collagen nanofibers for urethral regeneration via in situ polarization of M2 macrophages.

In situ tissue engineering utilizes the regenerative potential of the human body to control cell function for tissue regeneration and has shown considerable prospect in urology. However, many problems are still to be understood, especially the interactions between scaffolds and host macrophages at the wound site and how these interactions direct tissue integration and regeneration. This study was designed to evaluate the efficacy of hyaluronic acid (HA) functionalized collagen nanofibers in modulating the pro-healing phenotype expression of macrophages for urethral regeneration. Tubular HA-collagen nanofibers with HA-coating were prepared by coaxial electrospinning. The formation of a thin HA-coating atop each collagen nanofiber endowed its nanofibrous mats with higher anisotropic wettability and mechanical softness. The macrophages growing on the surface of HA-collagen nanofibers showed an elongated shape, while collagen nanofibers' surface exhibited a pancake shape. Immunofluorescence and ELISA analysis showed that elongation could promote the expression of M2 phenotype marker and reduce the secretion of inflammatory cytokines. In vivo experiments showed that tubular HA-collagen nanofibers significantly facilitate male puppy urethral regeneration after injury. In the regenerated urethra bridged by tubular HA-collagen nanofibers, anti-inflammatory M2 macrophages are recruited to the surface of the scaffold, which can promote angiogenesis and endogenous urothelial progenitor cell proliferation.

Color Doppler Ultrasound and Hemodynamics for Evaluating Graft Dysfunction in Recurrent Immunoglobulin A Nephropathy.

BACKGROUND The aim of this study was to investigate the diagnostic and prognostic utility of color Doppler ultrasound for graft dysfunction in recurrent immunoglobulin A nephropathy (IgAN). MATERIAL AND METHODS We selected a series of 78 biopsies diagnostic of recurrent IgAN following living-donor transplantation from July 2004 to January 2019. Based on Lee's classification, Doppler parameters in different degrees of histopathological injury were retrospectively analyzed. RESULTS The 4-year cumulative graft survival rate after biopsy was 66.3%, and the difference among the Kaplan-Meier curves of Lee's classification (P<0.01) was significant. Doppler parameters showed that echo enhancement, decreasing blood flow distribution, decreasing end-diastolic velocity (EDV) of the main renal artery (MRA), segmental renal atery (SRA) and interlobar renal artery (IRA), and an elevated resistance index (RI) of the arcuate renal artery (ARA) were significantly different among grades I-V of Lee's classification (P<0.05). Logistic multivariate analysis indicated that echo enhancement (HR 13.6, 95% CI 2.7-68.4) and decreasing EDV of the SRA (HR 1.1 for a 1-cm/s, 95% CI 1.0-1.2) were independent predictors of severe injury (IV-V). The ROC curve fitted by echo enhancement and decreasing EDV of the SRA had an area under the curve of 0.87. The cutoff was 17.5 cm/s (decreasing EDV of the SRA) without echo enhancement. The sensitivity and specificity were 72.2% and 91.7%, respectively. CONCLUSIONS Color Doppler ultrasound successfully evaluated the graft dysfunction in recurrent IgAN; a decreasing EDV of the SRA indicated severe histopathological injury and poor prognosis.

Ambulatory Orchidopexy Is a Potential Solution to Improve the Rate of Timely Repair in Cryptorchid Boys: An 8 Year Retrospective Study of 4,972 Cases.

Background: Cryptorchidism is the most common congenital anomaly in pediatric urology. Although early surgery on cryptorchid boys is recommended by pediatric urologists worldwide, the actual age at orchidopexy is often older than the recommended age. Our medical center has started performing ambulatory orchidopexy since March 2016 at the ambulatory surgery center. We aimed to investigate whether ambulatory orchidopexy can improve the timely repair rate. Methods: A retrospective analysis was conducted from 2012 to 2019 at our medical center. Ambulatory orchidopexy was started at our medical center on March 24, 2016. Boys born on or after September 24, 2015 were classified into the "with ambulatory medical resource" group, and boys born before September 24, 2014, were classified into the "without ambulatory medical resource" group. The timely repair rates were calculated and compared. Results: A total of 4,972 cryptorchidism cases were included in the final study. Approximately 33.0% of cryptorchid boys received timely surgery (orchidopexy by the age of 18 months), and only 6.8% of all cryptorchid boys underwent surgery before the age of 1 year. After the performance of ambulatory orchidopexy, the timely repair rate increased from 25.7 to 37.0% (P < 0.001), and the percentage of patients receiving surgery before the age of 1 year increased significantly from 3.5 to 8.6% (P < 0.001). The proportion of timely repair in patients with ambulatory medical resources was significantly higher than that in patients without ambulatory medical resources (15.6% vs. 58.2%, P < 0.001). Significant changes in the rate of surgery before 12 months of age were also found between the two groups (2.4% vs. 14.8%, P < 0.001). Conclusions: After the performance of ambulatory orchidopexy in our medical center, the rates of both timely repair and receiving surgery before the age of 1 year increased significantly. Ambulatory orchidopexy is a potential solution to improve the rate of timely repair in cryptorchid boys, and it is worthy of promotion in developing countries and regions.

Role of FTO gene polymorphisms in Wilms tumor predisposition: A five-center case-control study.

BACKGROUND: Wilms tumor is the most frequently occurring renal malignancy in pediatrics. The FTO gene exhibits a featured genetic contribution to cancer development. Nonetheless, its single nucleotide polymorphism (SNP) contribution to Wilms tumor remains unknown. METHODS: In the present study, 402 Wilms tumor patients and 1198 healthy controls were successfully genotyped for FTO gene SNPs (rs1477196 G>A, rs9939609 T>A, rs7206790 C>G and rs8047395 A>G) using TaqMan SNP genotyping assays. Odds ratios (ORs) and 95% confidence intervals (CIs), generated from unconditional logistic regression, were applied to quantify the effects of FTO gene SNPs on Wilms tumor risk. RESULTS: We found that the rs8047395 A>G polymorphism was significantly correlated with an increased risk for Wilms tumor (GG versus AA/AG: adjusted OR = 1.38, 95% CI = 1.04-1.85, p = 0.027). Carriers with 1 and 1-2 risk genotypes are more susceptible of developing Wilms tumor than those without risk genotypes. Stratified analysis of rs8047395 and risk genotypes revealed more significant relationships with Wilms tumor risk in certain subgroups. Preliminary functional annotations revealed that the rs8047395 A allele increases expression levels of the FTO gene as determined by expression quantitative trait locus analysis. CONCLUSIONS: The present study provides evidence that rs8047395 may regulate FTO gene expression and thus confer susceptibility to Wilms tumor. The candidate FTO gene rs8047395 A>G polymorphism identified in this study warrants independent investigation.

YTHDC1 gene polymorphisms and Wilms tumor susceptibility in Chinese children: A five-center case-control study.

Wilms tumor is a common pediatric tumor with abundant genetic drivers. YTHDC1 is an important reader of the N6-methyladenosine modification that widely regulates eukaryotic transcripts. YTHDC1 has been associated with the occurrence and development of some tumors. However, this is the first study on YTHDC1 gene polymorphisms and Wilms tumor susceptibility. In brief, we conducted a five-center case-control study to explore the associations between YTHDC1 polymorphisms (rs2293596 T > C, rs2293595 T > C, and rs3813832 T > C) and Wilms tumor susceptibility in Chinese children. A total of 404 cases and 1198 controls were successfully genotyped using TaqMan real-time PCR. Odds ratios (ORs) and 95% confidence intervals (CIs) were used as the evaluation indicators. We found that children with the 2-3 risk genotypes were more likely to develop Wilms tumor than those with the 0-1 risk genotypes (adjusted OR = 1.28, 95% CI = 1.01-1.62, P = 0.042). However, no other statistically significant results were found in this research study. The combined effect of YTHDC1 polymorphisms significantly increases Wilms tumor susceptibility. Our results need to be verified in different populations after increasing the sample size and controlling for confounding factors.