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As a widely used plasticizer, di-(2-ethylhexyl) phthalate (DEHP) is known to induce significant testicular injury. However, the potential mechanism and effects of pubertal exposure to DEHP on testis development remain unclear. In vivo, postnatal day (PND) 21 male rats were gavaged with 0, 250, and 500 mg/kg DEHP for ten days. Damage to the seminiferous epithelium and disturbed spermatogenesis were observed after DEHP exposure. Meanwhile, oxidative stress-induced injury and pyroptosis were activated. Both endoplasmic reticulum (ER) stress and mitophagy were involved in this process. Monoethylhexyl phthalate (MEHP) was used as the biometabolite of DEHP in vitro. The GC-1 and GC-2 cell lines were exposed to 0, 100 μM, 200 μM, and 400 μM MEHP for 24 h. Reactive oxygen species (ROS) generation, oxidative stress damage, ER stress, mitophagy, and pyroptosis were significantly increased after MEHP exposure. The ultrastructure of the ER and mitochondria was destroyed. X-box binding protein 1 (XBP1) was observed to be activated and translocated into the nucleus. ROS generation was inhibited by acetylcysteine. The levels of antioxidative stress, ER stress, mitophagy, and pyroptosis were decreased as well. After the administration of the ER stress inhibitor 4-phenyl-butyric acid, both mitophagy and pyroptosis were inhibited. Toyocamycin-induced XBP1 down-regulation decreased the levels of mitophagy and pyroptosis. The equilibrium between pyroptosis and mitophagy was disturbed by XBP1 accumulation. In summary, our findings confirmed that DEHP induced a ROS-mediated imbalance in pyroptosis and mitophagy in immature rat testes via XBP1. Moreover, XBP1 might be the key target in DEHP-related testis dysfunction.

Abstract Background Acute renal injury (AKI) after aortic arch reconstruction with cardiopulmonary bypass leads to injury of multiple organs and increases perioperative mortality. The study was performed to explore risk factors for AKI. We aim to develop a prediction model that can be used to accurately predict AKI through machine learning (ML). Methods A retrospective analysis was performed on 134 patients with aortic arch reconstruction with cardiopulmonary bypass who were treated at our hospital from January 2002 to January 2022. Risk factors for AKI were compositive and were evaluated with comprehensive analyses. Six artificial intelligence (AI) models were used for machine learning to build prediction models and to screen out the best model to predict AKI. Results Weight, eGFR, cyanosis, PDA, newborn birth and duration of renal ischemia were closely related to AKI. By integrating the results of the training cohort and validation cohort, we finally confirmed that the logistic regression model was the most stable model among all the models, and the logistic regression model showed good discrimination, calibration and clinical practicability. Based on 6 independent factors, the dynamic nomogram can be used as a predictive tool for clinical application. Conclusions DHCA could be considered in aortic arch reconstruction if additional perfusion of lower body were not performed especially when renal ischemia is greater than 30 min. Machine Learning models should be developed for early recognition of AKI. Trial Registration: ChiCTR, ChiCTR2200060552. Registered 4 june 2022. Graphical Abstract

Research on evapotranspiration and its drivers in the Aksu River Basin from the perspectives of climate change and land use is of great significance for promoting the efficient use and precise allocation of its water resources. Theil-Sen median trend analysis (T-S) and the Mann–Kendall nonparametric test (M-K), in addition to correlation analysis, partial correlation analysis, complex correlation analysis, and driving-factor zoning principles, were used to examine the characteristics of the spatiotemporal changes in evapotranspiration and to explore the driving mechanism of the changes in evapotranspiration. The results indicated that the range of fluctuations in the multiyear average evapotranspiration in the Aksu River Basin from 2001 to 2020 was between 481.58 and 772.37 mm/a, which showed the spatial distribution characteristics of being high in the west and central part of the basin, and low in the north and south of the basin. The positive correlation between evapotranspiration and precipitation was stronger, and the negative correlations with temperature and relative humidity were stronger. The change in evapotranspiration in cultivated land is mainly driven by precipitation and relative humidity × precipitation; for grassland, the main drivers were relative humidity and precipitation × relative humidity; for woodland, the main drivers were relative humidity and other climatic factors; and for other land types, the main drivers were other climatic factors.

Background. Kidney transplantation (KT) is the best treatment for end-stage renal disease. Although long and short-term survival rates for the graft have improved significantly with the development of immunosuppressants, acute rejection (AR) remains a major risk factor attacking the graft and patients. The innate immune response plays an important role in rejection. Therefore, our objective is to determine the biomarkers of congenital immunity associated with AR after KT and provide support for future research. Materials and Methods. A differential expression genes (DEGs) analysis was performed based on the dataset GSE174020 from the NCBI gene Expression Synthesis Database (GEO) and then combined with the GSE5099 M1 macrophage-related gene identified in the Molecular Signatures Database. We then identified genes in DEGs associated with M1 macrophages defined as DEM1Gs and performed gene ontology (GO) and Kyoto Encyclopedia of Genomes (KEGG) enrichment analysis. Cibersort was used to analyze the immune cell infiltration during AR. At the same time, we used the protein–protein interaction (PPI) network and Cytoscape software to determine the key genes. Dataset, GSE14328 derived from pediatric patients, GSE138043 and GSE9493 derived from adult patients, were used to verify Hub genes. Additional verification was the rat KT model, which was used to perform HE staining, immunohistochemical staining, and Western Blot. Hub genes were searched in the HPA database to confirm their expression. Finally, we construct the interaction network of transcription factor (TF)-Hub genes and miRNA-Hub genes. Results. Compared to the normal group, 366 genes were upregulated, and 423 genes were downregulated in the AR group. Then, 106 genes related to M1 macrophages were found among these genes. GO and KEGG enrichment analysis showed that these genes are mainly involved in cytokine binding, antigen binding, NK cell-mediated cytotoxicity, activation of immune receptors and immune response, and activation of the inflammatory NF-κB signaling pathway. Two Hub genes, namely CCR7 and CD48, were identified by PPI and Cytoscape analysis. They have been verified in external validation sets, originated from both pediatric patients and adult patients, and animal experiments. In the HPA database, CCR7 and CD48 are mainly expressed in T cells, B cells, macrophages, and tissues where these immune cells are distributed. In addition to immunoinfiltration, CD4+T, CD8+T, NK cells, NKT cells, and monocytes increased significantly in the AR group, which was highly consistent with the results of Hub gene screening. Finally, we predicted that 19 TFs and 32 miRNAs might interact with the Hub gene. Conclusions. Through a comprehensive bioinformatic analysis, our findings may provide predictive and therapeutic targets for AR after KT.

AbstractHuman umbilical cord mesenchymal stem cells (hucMSCs) have been shown to improve kidney injury. Exosomes have been indicated to be important mediators of renal protection in MSC therapy. In spite of this, the mechanism remains unclear. Our study investigated how exosomes derived from hucMSCs (hucMSC-Ex) improve acute kidney injury (AKI). Exosomes were extracted by using an ultracentrifugation technique and identified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot. Twenty-four male SD rats were randomly divided into four groups: sham group, sham + hucMSC-Ex group, ischemia–reperfusion injury (IRI) group, and IRI + hucMSC-Ex group. In vitro, we treated rat proximal renal tubular epithelial cell line (NRK-52E) with cisplatin to mimic in vivo models of AKI. The NRK-52E cells were treated with or without 160 μg/mL hucMSC-Ex, and 1 µg/mL cisplatin was added after 9 h. Cells were harvested after 24 h. In the IRI group, the levels of serum creatinine (Scr) and blood urea nitrogen (BUN) were increased; renal tubules were dilated, epithelial cells were vacuolated, and collagen fibers were deposited in the renal interstitium. After treatment with cisplatin, the NRK-52E cells displayed pyroptotic morphology characterized by pyroptotic bodies. The protein expression levels of fibronectin, α-smooth muscle actin (α-SMA), vimentin, gasdermin D (GSDMD), caspase-1, interleukin-1 (IL-1β) and NLRP3 in IRI tissues and in cisplatin treatment NRK-52E cells were significantly upregulated. However, after the hucMSC-Ex intervention, kidney injury was effectively improved in vivo and in vitro. The current study shows that pyroptosis is involved in AKI and that hucMSC-Ex improves AKI by inhibiting pyroptosis.

Abstract Background Kidney insults due to various pathogenic factors, such as trauma, infection, and inflammation, can cause tubular epithelial cell injury and death, leading to acute kidney injury and the transformation of acute kidney injury to chronic kidney disease. There is no definitive treatment available. In previous studies, human umbilical cord mesenchymal stem cells have been shown to promote kidney injury. In this preclinical study, we investigate the role and mechanism of human umbilical cord mesenchymal stem cell exosomes (HucMSC-Exos) on the repair of renal tubular epithelial cells after injury. Methods C57BL/6 mice underwent unilateral ureteral obstruction, and epithelial cell injury was induced in HK-2 cells by cisplatin. HucMSC-Exos were assessed in vivo and in vitro. The extent of renal cell injury, activation of necroptosis pathway, and mitochondrial quality-control-related factors were determined in different groups. We also analyzed the possible regulatory effector molecules in HucMSC-Exos by transcriptomics. Results HucMSC-Exo inhibited necroptosis after renal tubular epithelial cell injury and promoted the dephosphorylation of the S637 site of the Drp1 gene by reducing the expression of PGAM5. This subsequently inhibited mitochondrial fission and maintained mitochondrial functional homeostasis, mitigating renal injury and promoting repair. In addition, HucMSC-Exo displayed a regulatory role by targeting RIPK1 through miR-874-3p. Conclusion The collective findings of the present study demonstrate that HucMSC-Exos can regulate necroptosis through miR-874-3p to attenuate renal tubular epithelial cell injury and enhance repair, providing new therapeutic modalities and ideas for the treatment of AKI and the process of AKI to CKD transformation to mitigate renal damage.

Osteosarcoma is a bone tumor with a high incidence in children and adolescents. Chemotherapy for osteosarcoma is limited, and effective targeted drugs are urgently needed to treat osteosarcoma. Exosomes as a natural nano drug delivery platform have been widely studied and proven to have good drug delivery performance. However, the low production of exosomes hinders its development as a carrier. Exosome mimetics (EMs) as an alternative product of exosomes solve the problem of low production of exosomes and maintain the good performance of exosomes as carriers. In this study, bone marrow mesenchymal stem cells (BMSCs) were sequentially extruded to generate EMs to encapsulate doxorubicin (EM-Dox) to treat osteosarcoma. The results showed that we successfully prepared EMs of BMSC, and EM-Dox was prepared using an active-loading approach. Our engineered EM-Dox demonstrated significantly more potent tumor inhibition activity and fewer side effects than free doxorubicin. This novel biological nanomedicine system provides a promising opportunity to develop novel precision medicine for osteosarcoma.

Abstract Objective To discuss the clinical and prognostic indicators of pediatric malignant rhabdoid tumor of the kidney (MRTK), and to increase the understanding of the occurrence and development of MRTK. Methods From July 2014 to September 2021, all cases were confirmed by postoperative pathological examination. Among the 42 patients, there were 25 males and 17 females, with a median age of 10 (1–84) months. Abdominal mass or hematuria were the main clinical manifestations. Preoperative chemotherapy was performed in 9 cases (VC). The tumor stages were stage I-IV. Preoperative metastasis was found in 9 cases; the most common site was the lung. Postoperative patients received conventional chemotherapy, including VDACE regimen and UH-1 regimen. Among the 42 children in this group, survival at follow-up in this study was 26.2%(11/42). Results Preoperative anemia was found by univariate analysis, hypertension and hypercalcemia had shorter survival time. In addition, tumor-related factors had a significant impact on survival, with incomplete tumor resection, lymph node metastasis, stage III-IV had a lower survival rate. The impact of postoperative factors on survival included postoperative complications had a lower survival rate. The children were younger than 12 months, preoperative metastasis, no chemotherapy was performed after surgery was an independent risk factor for the prognosis of MRTK. Conclusion The main clinical manifestations about MRTK were abdominal mass and hematuria. Preoperative chemotherapy did not significantly improve the prognosis. Postoperative chemotherapy can significantly improve the survival rate. Diagnosis depends on clinical manifestations, imaging, histopathology, immunohistochemistry and other comprehensive judgment. Age less than 12 months, preoperative metastasis, and no postoperative chemotherapy were independent risk factors for prognosis.

Abstract Background Exosomes derived from mesenchymal stem cells (MSCs) have shown to have effective application prospects in the medical field, but exosome yield is very low. The production of exosome mimetic vesicles (EMVs) by continuous cell extrusion leads to more EMVs than exosomes, but whether the protein compositions of MSC-derived EMVs (MSC-EMVs) and exosomes (MSC-exosomes) are substantially different remains unknown. The purpose of this study was to conduct a comprehensive proteomic analysis of MSC-EMVs and MSC-exosomes and to simply explore the effects of exosomes and EMVs on wound healing ability. This study provides a theoretical basis for the application of EMVs and exosomes. Methods In this study, EMVs from human umbilical cord MSCs (hUC MSCs) were isolated by continuous extrusion, and exosomes were identified after hUC MSC ultracentrifugation. A proteomic analysis was performed, and 2315 proteins were identified. The effects of EMVs and exosomes on the proliferation, migration and angiogenesis of human umbilical vein endothelial cells (HUVECs) were evaluated by cell counting kit-8, scratch wound, transwell and tubule formation assays. A mouse mode was used to evaluate the effects of EMVs and exosomes on wound healing. Results Bioinformatics analyses revealed that 1669 proteins in both hUC MSC-EMVs and hUC MSC-exosomes play roles in retrograde vesicle-mediated transport and vesicle budding from the membrane. The 382 proteins unique to exosomes participate in extracellular matrix organization and extracellular structural organization, and the 264 proteins unique to EMVs target the cell membrane. EMVs and exosomes can promote wound healing and angiogenesis in mice and promote the proliferation, migration and angiogenesis of HUVECs. Conclusions This study presents a comprehensive proteomic analysis of hUC MSC-derived exosomes and EMVs generated by different methods. The tissue repair function of EMVs and exosomes was herein verified by wound healing experiments, and these results reveal their potential applications in different fields based on analyses of their shared and unique proteins.

Abstract Purpose Extralevator (ELAPE) and abdominoperineal excision (APE) are two major surgical approaches for low rectal cancer patients. Although excellent short-term efficacy is achieved in patients undergoing ELAPE, the long-term benefits have not been established. In this study we evaluated the safety, pathological and survival outcomes in rectal cancer patients who underwent ELAPE and APE. Methods One hundred fourteen patients were enrolled, including 68 in the ELAPE group and 46 in the APE group at the Beijing Chaoyang Hospital, Capital Medical University from January 2011 to November 2020. The baseline characteristics, overall survival (OS), progression-free survival (PFS), and local recurrence-free survival (LRFS) were calculated and compared between the two groups. Results Demographics and tumor stage were comparable between the two groups. The 5-year PFS (67.2% versus 38.6%, log-rank P = 0.008) were significantly improved in the ELAPE group compared to the APE group, and the survival advantage was especially reflected in patients with pT3 tumors, positive lymph nodes or even those who have not received neoadjuvant chemoradiotherapy. Multivariate analysis showed that APE was an independent risk factor for OS (hazard ratio 3.000, 95% confidence interval 1.171 to 4.970, P = 0.004) and PFS (hazard ratio 2.730, 95% confidence interval 1.506 to 4.984, P = 0.001). Conclusion Compared with APE, ELAPE improved long-term outcomes for low rectal cancer patients, especially among patients with pT3 tumors, positive lymph nodes or those without neoadjuvant chemoradiotherapy.

BackgroundRenal ischemia reperfusion injuries (IRIs) are very common in clinical diagnoses and treatments, which are a common cause of impaired renal functions, worsening pathological damage, affecting disease progression and hindering recovery. Renal IRIs are an inflammatory disease mediated by the adaptive and innate immune system. There is a complex interaction between oxidative stress and immune cell infiltration. Therefore, we aimed to determine biomarkers associated with oxidative stress during renal IRIs and their relationship with immune cell infiltration.MethodA differential gene expression analysis was made based on the GSE148420 dataset from the NCBI Gene Expression Comprehensive Database (GEO) combined with 92 oxidative-stress (OS)-related genes identified in the Molecular Signatures Database. Then we identified differentially-expressed genes (DEOSGs) associated with oxidative stress, which were used for gene ontology (GO) and a Kyoto Encyclopedia of Genomes (KEGG) enrichment analysis. At the same time, we used PPI protein interaction networks and Lasso regression analysis to identify key genes, which were verified by the validation sets GSE58438 and GSE71647, as well as Western Blot detection on rat renal IRI models. At the same time, PAS staining, HE staining and immunohistochemistry were used to detect tissue damage and expression of markers related to oxidative stress during renal ischemia-reperfusion. Single-gene enrichment analysis (GSEA) was used to further clarify the underlying biological functions of key genes. Cibersort was used to analyze the immune cell infiltration during renal IRI and the correlation of key genes with immune cells. At the same time, we constructed a network of transcription-factor (TF)-Hub genes and miRNA-Hub genes. DGIDB was used to predict drugs and molecular compounds that might interact with the Hub genes.ResultsCompared with the control group, a total of 5456 differential genes (DEGs) were measured in the renal IRI group, 2486 of which were upregulated and 2970 were down-regulated. Among them, we found 30 DEGs (DEOSGs) associated with oxidative stress. The results of GO and KEGG enrichment analysis showed that these DEOSGs were mainly enriched in glutathione metabolism, the response to oxidative stress stimulation, the regulation of T cell activation and apoptosis signaling pathways. Through a protein interaction network (PPI) and a LASSO regression analysis, a total of two Hub genes were identified, namely GPX3 and GSTT1, which were validated through external validation sets and animal experiments. Through pathological methods, we found that the pathological damage of renal tissue and the expression of oxidative stress markers increased after renal ischemia-reperfusion. The results of GSEA showed that the Hub genes were related to oxidative stress pathways, apoptosis signaling pathways and immune-response-related signaling pathways. An immunoinfiltration correlation analysis showed that genes GPX3 and GSTT1 were significantly positively correlated with plasma cells and macrophage M0, while were negatively correlated with monocytes and macrophages M1 and M2. Using the Strust, Starbase and DGIDB database, we predicted that 81 transcription factors, 49 miRNAs and 13 drug or molecular compounds might interact with the Hub genes.ConclusionThrough a comprehensive analysis of gene expression, our findings may provide new potential biomarkers for the pathogenesis of renal IRIs and a reliable basis for its early diagnosis as well as treatment.

Maintaining the balance of a cell’s redox function is key to determining cell fate. In the critical redox system of mammalian cells, glutathione peroxidase (GPX) is the most prominent family of proteins with a multifaceted function that affects almost all cellular processes. A total of eight members of the GPX family are currently found, namely GPX1-GPX8. They have long been used as antioxidant enzymes to play an important role in combating oxidative stress and maintaining redox balance. However, each member of the GPX family has a different mechanism of action and site of action in maintaining redox balance. GPX1-4 and GPX6 use selenocysteine as the active center to catalyze the reduction of H2O2 or organic hydroperoxides to water or corresponding alcohols, thereby reducing their toxicity and maintaining redox balance. In addition to reducing H2O2 and small molecule hydroperoxides, GPX4 is also capable of reducing complex lipid compounds. It is the only enzyme in the GPX family that directly reduces and destroys lipid hydroperoxides. The active sites of GPX5 and GPX7-GPX8 do not contain selenium cysteine (Secys), but instead, have cysteine residues (Cys) as their active sites. GPX5 is mainly expressed in epididymal tissue and plays a role in protecting sperm from oxidative stress. Both enzymes, GPX7 and GPX8, are located in the endoplasmic reticulum and are necessary enzymes involved in the oxidative folding of endoplasmic reticulum proteins, and GPX8 also plays an important role in the regulation of Ca2+ in the endoplasmic reticulum. With an in-depth understanding of the role of the GPX family members in health and disease development, redox balance has become the functional core of GPX family, in order to further clarify the expression and regulatory mechanism of each member in the redox process, we reviewed GPX family members separately.

Purpose: Considerable debates exist regarding the preferable technique to repair a paediatric inguinal hernia (PIH). This systematic review aims to compare the efficacy and safety of laparoscopic herniorrhaphy (LH) and open herniorrhaphy (OH) in PIH. Methods: The randomised controlled trials (RCTs) that compared the outcomes of LH and OH in PIH without region and language restrictions searched from the following databases: PubMed, Web of Science Database, Cochrane Library, SciELO Citation Index, Russian Science Citation Index, China National Knowledge Infrastructure, WanFang Data and China Science and Technology Journal Database. Results: A total of 13 RCTs that involving 1207 patients included in the review. The LH displayed a shorter operative time for bilateral hernia repair (weighted mean difference = −8.23, 95% confidence interval [CI]: −11.22~−5.23, P < 0.00001), a lower complication rate (odds ratio [OR] = 0.32, 95% CI: 013–0.83, P = 0.02) along with a lower wound infection (OR = 0.14, 95% CI: 0.04–0.55, P = 0.005) and major male-specific post-operative complications (OR = 0.10, 95% CI: 0.04–0.24, P < 0.00001) and a less contralateral metachronous inguinal hernia (CMIH) incidence rate (OR = 0.09, 95% CI: 0.02–0.42, P = 0.002). No significant difference was found for unilateral operative time, time to full recovery, length of hospital stay, recurrence and hydrocele rates between the two techniques. Conclusion: The present review reiterates that both the LH and OH techniques for the PIH repair are comparable. However, in some aspects, the LH is superior to the OH in terms of operative time for bilateral hernias, post-operative complications rate and CMIH incidence rate. Rigorously designed RCTs are anticipated to confirm the clinical effects of both LH and OH.

Abstract Background To investigate the association between geographic, clinical, socioeconomic factors and delayed management of pediatric testicular torsion (TT) in West China. Methods A retrospective study was conducted on TT at Children’s Hospital of Chongqing Medical University in West China from November 2004 to December 2020. Univariate analysis and logistic regression analysis were conducted to determine the association between these factors and delayed management of TT. Results A total of 301 cases were included in this study. The misdiagnosis rate of TT in primary, secondary healthcare units and tertiary hospitals was 93.8, 71.1, and 8.9%, respectively. Approximately 26.9% of TT boys received timely surgical management (within 12 h from symptoms inset to surgery). Logistic regression analyses suggested the following factors were associated with delayed repair of TT: age less than 6 years (P = 0.001), with a history of symptoms progress (P = 0.001) or former treatment (P

PurposePediatric testicular yolk sac tumor is a rare malignant germ cell tumor and there is a lack of large clinical studies. The purpose of this study is to summarize the clinical characteristics of pediatric testicular yolk tumor and evaluate the prognostic factors.Materials and methodsThe medical records of children with testicular yolk sac tumor in one pediatric medical centre in China from January 2005 to January 2021 were retrospectively investigated. Data regarding clinical characteristics, treatment and prognosis were collected.ResultsA total of 109 patients with a median diagnosed age of 18 months (range 2–69) were included in this study; of them 100 were diagnosed as stage I, 6 as stage II and 3 as stage IV. All patients underwent radical orchiectomy, and 61 of them underwent postoperative chemotherapy. The mean follow-up time was 61.3 months (range 3–259), during that time, 8 patients experienced relapse. The five-year overall survival was 90.6% (95% CI 84.6%–96.7%). Univariate Cox regression analysis showed that disease stage, relapse, maximum tumor diameter, and alpha-fetoprotein returning to normal within 2 months postoperatively were risk factors for survival (HRs of 25.43, 26.43, 1.48 and 0.08, respectively, p

PurposeTo establish a predictive model for upper urinary tract damage (UUTD) in children with neurogenic bladder (NB) and verify its efficacy.MethodsA retrospective study was conducted that consisted of a training cohort with 167 NB patients and a validation cohort with 100 NB children. The clinical data of the two groups were compared first, and then univariate and multivariate logistic regression analyses were performed on the training cohort to identify predictors and develop the nomogram. The accuracy and clinical usefulness of the nomogram were verified by receiver operating characteristic (ROC) curve, calibration curve and decision curve analyses.ResultsThere were no significant differences in other parameters between the training and validation cohorts except for age (all P > 0.05). Recurrent urinary tract infection, bladder compliance, detrusor leak point pressure, overactive bladder and clean intermittent catheterization were identified as predictors and assembled into the nomogram. The nomogram showed good discrimination with the area under the ROC curve (AUC) in the training cohort (0.806, 95% CI: 0.737–0.874) and validation cohort (0.831, 95% CI: 0.753–0.0.909). The calibration curve showed that the nomograms were well calibrated, with no significant difference between the predicted and observed probabilities. Decision curve analysis indicated that the nomogram has good clinical applicability.ConclusionThis study presents an effective nomogram incorporating five clinical characteristics that can be conveniently applied to assess NB children' risk of progressing to UUTD.

AimTo analyze locally advanced rectal cancer (LARC) patients and tumor characteristics during the period of total neoadjuvant therapy (TNT) and explore the risk factors that may predict poor tumor regression in response to TNT.Materials and methodsThe data of 120 LARC patients who received TNT from December 2016 and September 2019 in our hospital were retrospectively analyzed. The clinicopathological characteristics of patients with different tumor regression responses were compared. Then we divided patients into two groups according to the carcinoembryonic antigen (CEA) clearance pattern after chemoradiation to explore risk factors that might predict the tumor regression response.ResultsOf 120 LARC patients, 34 (28.3%) exhibited poor regression. Stratified analysis by tumor response showed that patients with poor response to TNT were more likely to obtain elevated CEA during the course of TNT (all P < 0.05). For those with elevated pretreatment CEA, fewer patients with poor response obtained normal CEA after chemoradiation (13.6% vs. 72.7%, P < 0.001). Besides, less patients’ CEA levels in the poor response group decreased by greater than 50% after chemoradiation when compared with that in the good response group (18.2% vs. 60.6%, P = 0.002). Stratified analysis by CEA clearance pattern after chemoradiation showed patients who obtained an elevated pretreatment CEA and decreased by less than 50% after chemoradiation were more likely to have poor response to TNT compared to others (76.2% vs. 18.2%, P < 0.001). Logistic multivariate analysis revealed that cN2 (95% CI 1.553-16.448), larger tumors (95% CI 2.250-21.428) and CEA clearance pattern after chemoradiation (95% CI 1.062-66.992) were independent risk factors for poor tumor regression response.ConclusionApproximately one-fourth of LARC patients with TNT achieved a poor regression response. Here, cN2, larger tumor size before treatment and elevated CEA levels were considered predictive features of a poor response. Active surveillance of CEA levels during the TNT course are potentially important, and CEA levels after chemoradiation might have important implications for the tumor response to TNT.

Most children with a neurogenic bladder (NB) have bladder fibrosis, which causes irreversible bladder dysfunction and damage to the upper urinary tract. However, the mechanism of bladder fibrosis remains unclear. This study aimed to investigate the underlying causes of bladder fibrosis. Here, the lumbar 6 (L6) and sacral 1 (S1) spinal nerves of Sprague Dawley rats were severed bilaterally to establish NB models. Using RNA-seq, we discovered that the NF-κB signaling pathway and inflammation were upregulated in spinal cord injury (SCI)-induced bladder fibrosis. Subsequent Western blotting, enzyme-linked immunosorbent assays, immunohistochemical staining, and immunofluorescence staining verified the RNA-seq findings. To further clarify whether the NF-κB signaling pathway and pyroptosis were involved in bladder fibrosis, a TGF-β1-treated urinary epithelial cell line (SV-HUC-1 cells) was used as an in vitro model. Based on the results of RNA-seq, we consistently found that the NF-κB signaling pathway and pyroptosis might play important roles in TGF-β1-treated cells. Further experiments also confirmed the RNA-seq findings in vitro. Moreover, using the NLRP3 inhibitor MCC950 rescued TGF-β1-induced fibrosis, and the NF-κB signaling pathway inhibitor BAY 11-7082 effectively rescued TGF-β1-induced pyroptosis and the deposition of extracellular matrix by SV-HUC-1 cells. In summary, our research demonstrated for the first time that the NF-κB signaling pathway inhibition rescued bladder epithelial cells pyroptosis and fibrosis in neurogenic bladders.

With the increasing complexity of the electromagnetic environment, existing electronic systems and various equipment are greatly threatened. The study of the assessment of the effects of the electromagnetic environment has attracted more and more attention in the academic field and industry. In this review, the definition of the electromagnetic environmental effects assessment could be classified into two categories: objective and subjective equipment electromagnetic environmental effect assessments. Studies on both are comprehensively reviewed. The electromagnetic environmental effect assessment models are described and analyzed. The effects evaluation models mainly calculate the electromagnetic environmental effect index by various weighting, probability, and normalized interference level methods. However, each proposed model has certain limitations, so it cannot deal with all the electromagnetic interference effects. Therefore, a comprehensive evaluation model for complex electromagnetic environmental effects has not yet been established. Recent studies have shown that neural networks can be used to improve the adaptability of evaluation models in electromagnetic environments. The evaluation result of the normalized interference level method is more consistent with the actual work efficiency. The combination of the two can unify the objective and subjective assessments, which is of great significance to the improvement of the consistency and accuracy of the results of the effects evaluation of the electromagnetic environment. Accordingly, challenges for future research are revealed, which plays a vital role in the development of electromagnetic environmental effects research and provides a reference for researchers.

Difenoconazole (DFZ) is a broad-spectrum triazole fungicide that is widely utilized in agriculture. Although DFZ has been demonstrated to induce reproductive toxicity in aquatic species, its toxic effects on the mammalian reproductive system have yet to be fully elucidated. In vivo, male mice were administered 0, 20 or 40 mg/kg/d of DFZ via oral gavage for 35 days. Consequently, DFZ significantly decreased testicular organ coefficient, sperm count and testosterone levels, augmented sperm malformation rates, and elicited histopathological alterations in testes. TUNEL assay showed increased apoptosis in testis. Western blotting results suggested abnormally high expression of the sperm meiosis-associated proteins STRA8 and SCP3. The concentrations of retinoic acid (RA), retinaldehyde (RE), and retinol (ROL) were increased in the testicular tissues of DFZ-treated groups. The mRNA expression level of genes implicated in RA synthesis significantly increased while genes involved in RA catabolism significantly decreased. In vitro, DFZ reduced cell viability and increased RA, RE, and ROL levels in GC-2 cells. Transcriptome analysis revealed a significant enrichment of numerous terms associated with the RA pathway and apoptosis. The qPCR experiment verified the transcriptome results. In conclusion, our results indicate that DFZ exposure can disrupt RA signaling pathway homeostasis, and induce testicular injury in mice testes.

Purpose: Develop and validate an accessible prediction model using machine learning (ML) to predict the risk of chemotherapy-induced myelosuppression (CIM) in children with Wilms’ tumor (WT) before chemotherapy is administered, enabling early preventive management. Methods: A total of 1433 chemotherapy cycles in 437 children with WT who received chemotherapy in our hospital from January 2009 to March 2022 were retrospectively analyzed. Demographic data, clinicopathological characteristics, hematology and blood biochemistry baseline results, and medication information were collected. Six ML algorithms were used to construct prediction models, and the predictive efficacy of these models was evaluated to select the best model to predict the risk of grade ≥ 2 CIM in children with WT. A series of methods, such as the area under the receiver operating characteristic curve (AUROC), the calibration curve, and the decision curve analysis (DCA) were used to test the model’s accuracy, discrimination, and clinical practicability. Results: Grade ≥ 2 CIM occurred in 58.5% (839/1433) of chemotherapy cycles. Based on the results of the training and validation cohorts, we finally identified that the extreme gradient boosting (XGB) model has the best predictive efficiency and stability, with an AUROC of up to 0.981 in the training set and up to 0.896 in the test set. In addition, the calibration curve and the DCA showed that the XGB model had the best discrimination and clinical practicability. The variables were ranked according to the feature importance, and the five variables contributing the most to the model were hemoglobin (Hgb), white blood cell count (WBC), alkaline phosphatase, coadministration of highly toxic chemotherapy drugs, and albumin. Conclusions: The incidence of grade ≥ 2 CIM was not low in children with WT, which needs attention. The XGB model was developed to predict the risk of grade ≥ 2 CIM in children with WT for the first time. The model has good predictive performance and stability and has the potential to be translated into clinical applications. Based on this modeling and application approach, the extension of CIM prediction models to other pediatric malignancies could be expected.

BackgroundUrinary tract infection (UTI) is a common occurrence in children. UTI and urological malformations are intimately linked. However, whether urinary tract malformations affect the clinical features of pediatric UTI remains unclear. The purpose of this study was to characterize the clinical features and microbial etiology of UTI in children.MethodsWe retrospectively reviewed the records of 741 patients with UTI treated at the Chongqing Medical University Affiliated Children's Hospital between 2015 and 2020. Patients with and without urological malformations were compared using propensity score matching (PSM).ResultsEscherichia coli was the most common causative microorganism of UTI, accounting for 40.5% of infections. One hundred twenty-two patients (16.5%) had urological malformations. PSM identified 122 matched pairs of patients with or without urological malformations. The proportion of patients with UTI caused by atypical microorganisms was significantly higher in patients with urological malformations (P = 0.048). Children with urological malformations showed longer duration of intravenous antibiotic treatment (P = 0.010), higher cost of treatment (P < 0.001), and higher prevalence of recurrence (23.8 vs. 10.7%, P < 0.001), compared with the normal group.ConclusionChildren with urological malformations are more likely to develop UTI with atypical microorganisms. Appropriate imaging examination and urine culture are strongly recommended for the diagnosis and management of pediatric UTI.

PurposeTo compare the safety, efficacy, and cosmetic results of single-incision scrotal orchiopexy (SISO) and traditional two-incision inguinal orchiopexy (TTIO) for primary palpable undescended testes (PUDTs) in children.Materials and MethodsA systematic literature search of all relevant studies published on PubMed, Embase, Medline, Cochrane Library, Web of Science database, and Wanfang data until July 2021 was conducted. The operative time, hospitalization duration, conversion rate, wound infection or dehiscence, scrotal hematoma or swelling, testicular atrophy, reascent, hernia or hydrocele, analgesics needs, and cosmetic results were compared between SISO and TTIO using the Mantel–Haenszel or inverse-variance method.ResultsA total of 17 studies involving 2,627 children (1,362 SISOs and 1,265 TTIOs) were included in the final analysis. The conversion rate of SISO was 3.6%. The SISO approach had a statistically significant shorter operative time than the TTIO approach for PUDT (weighted mean difference−11.96, 95% confidence interval −14.33 to −9.59, I2 = 79%, P < 0.00001) and a shorter hospital stay (weighted mean difference−1.05, 95% confidence interval −2.07 to −0.03, P = 0.04). SISO needed fewer analgesics and had better cosmetic results than TTIO. SISO had a similar total, short-term, or long-term complication rate with TTIO.ConclusionCompared with TTIO, SISO has the advantages of shorter operative time, shorter hospitalization duration, less postoperative pain, and better cosmetic appealing results. SISO is a safe, effective, promising, and potential minimal invasive surgical approach for PUDT. SISO is an alternative to TTIO in selected cryptorchid patients, especially for lower positioned ones.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42021268562.

Thyroid hormone homeostasis is essential for normal brain development in fetuses and infants. Exposure to endocrine-disrupting chemicals (EDCs) during pregnancy is associated with compromised maternal thyroid homeostasis, and thus may lead to adverse neurodevelopmental outcomes in newborns. However, evidence regarding the association of prenatal EDC exposure and thyroid hormones in newborns is controversial. Therefore, a meta-analysis to elucidate the relationship between maternal exposure to EDCs and neonatal THs was performed. A systematic search of PubMed, EMBASE, and the Cochrane Library (CENTRAL) for relevant published studies that provided quantitative data on the association between prenatal EDC exposure and neonatal thyroid hormones was conducted in August 2021. To calculate the overall estimates, we pooled the adjusted β regression coefficients with 95% confidence intervals (CIs) from each study by the inverse variance method. The pooling results indicated that prenatal EDC exposure had no significant influence on neonatal TSH, TT3, FT3, TT4 or FT4 level in the global assessment. However, in the specific exposure and outcome assessment, we found that prenatal exposure to organochlorine (β coefficient, −0.022; 95% CI, −0.04 to −0.003) and PFAS (β coefficient, −0.017; 95% CI, −0.033 to 0) was negatively associated with neonatal TT4 level. In conclusion, prenatal exposure to organochlorine and PFAS may be associated with lower neonatal TT4 level.

PurposeThe purpose of this study is to provide a new strategy for non-cystoscopic double J urethral stent (JJS) removal, the transurethral retrograde fishing the double J urethral stent (TURFJJS), that avoids general anesthesia in pediatric populations.MethodsWe retrospectively reviewed the JJS removal records of patients having ureteropelvic junction obstruction (UPJO). We analyzed differences in the removal success rates, operation-related severe complications, total cost, duration, and parental satisfaction between TURFJJS and traditional cystoscopic double J urethral stent removal (CJJSR) procedures.ResultsA total of 324 patients with UPJO were included in this study. CJJSR yielded a success rate of 100%. TURFJJS achieved a success rate of 94.3%. The TURFJJS was just an outpatient procedure, and its total cost was about 800 Chinese yuan (US$ 124). There were no severe JJS removal-related complications using TURFJJS. Parental satisfaction was 98.2 and 92.5% for the CJJSR and TURFJJS protocols, respectively.ConclusionTURFJJS is safe, effective, cost-effective, and well-tolerated in pediatric patients, minimizing or eliminating the need for general anesthesia, additional hospitalization, and waste of time. TURFJJS should be widely used in pediatric urology.

Objective: The aim of this study was to identify a theoretical support for the prevention of urethral fistula following hypospadias repair, by comparing the preputial wound healing process in Sprague-Dawley (SD) rats with and without hypospadias induced by flutamide. Methods: Fifteen pregnant SD rats were randomly divided into three groups. These rats in one group received the androgen receptor antagonist flutamide (25 mg/kg/day) from gestation days 11–17, to establish a rat model of hypospadias for further study of the molecular mechanisms of the hypospadias etiology. The pregnant rats in the control groups were not administered flutamide. The pups from the control and experiment groups underwent an incision on the dorsal prepuce on postnatal day 25 and were sacrificed on postoperative days 3, 7, and 14 to collect penis samples. The penis morphology was examined in all groups. Subsequently, transforming growth factor β1 (TGF-β1), α-smooth muscle actin (α-SMactin), and signal transducers and activators of the transcription 3 (STAT3) expression levels in the different groups were measured at the indicated time points postoperatively using qRT-PCR and Western blot. Results: There was less regeneration of the subcutaneous tissue in hypospadias rats than in the sham-operated group (P

The reliability of distributed network is researched by establishing one set of effective modeling, analysis, evaluation, and optimization method theory, which is a hot research area in the distributed network system field. The phased analysis method is utilized to study the reliability of the distributed network including the analysis and definition of the distributed network on the basis of studying its operational process. Meanwhile, task request, task scheduling, and execution phase will be also studied, and the establishment of reliability mathematical model of distributed network will be discussed to provide actual reference significance for the design of the distributed network system.

Identifying suitable habitats for endangered species is critical in order to promote their recovery. However, conventional species distribution models (SDMs) need large amounts of labeled sample data to learn the relationship between species and environmental conditions, and are difficult to fully detangle the role of the environment in the distribution of the endangered species, which are very sparsely distributed and have environmental heterogeneity. This study’s first innovation used the semi-supervised model to accurately simulate the suitable habitats for endangered species with a small sample size. The model performance was compared with three conventional SDMs, namely Maxent, the generalized linear model, and a support vector machine. Applying the model to the endangered species Populus euphratica (P. euphratica) in the lower Tarim River basin (TRB), Northwest China. The results showed that the semi-supervised model exhibited better performance than conventional SDMs with an accuracy of 85% when only using 443 P. euphratica samples. All models developed using smaller sample sizes exhibit worse performance in the prediction of habitat suitability areas for endangered species while the semi-supervised model is still excellent. The results showed that the suitable habitat for P. euphratica is mainly near the river channel of the lower TRB, accounting for 13.49% of the study area. The lower Tarim River still has enormous land potential for the restoration of endangered P. euphratica . The model developed here can be used to evaluate a suitable habitat for endangered species with only a small sample size, and provide a basis for the conservation of endangered species.

This study aims to determine key genes and pathways that could play important roles in the spermatogenic process of patients with cryptorchidism. The gene expression profile data of GSE25518 was obtained from the Gene Expression Omnibus (GEO) database. Microarray data were analyzed using BRB-Array Tools to identify differentially expressed genes (DEGs) between high azoospermia risk (HAZR) patients and controls. In addition, other analytical methods were deployed, including hierarchical clustering analysis, class comparison between patients with HAZR and the normal control group, gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and the construction of a protein–protein interaction (PPI) network. In total, 1015 upregulated genes and 1650 downregulated genes were identified. GO and KEGG analysis revealed enrichment in terms of changes in the endoplasmic reticulum cellular component and the endoplasmic reticulum protein synthetic process in the HAZR group. Furthermore, the arachidonic acid pathway and mTOR pathway were also identified as important pathways, while RICTOR and GPX8 were indentified as key genes involved in the spermatogenic process of patients with cryptorchidism. In present study, we found that changes in the synthesis of endoplasmic reticulum proteins, arachidonic acid and the mTOR pathway are important in the incidence and spermatogenic process of cryptorchidism. GPX8 and RICTOR were also identified as key genes associated with cryptorchidism. Collectively, these data may provide novel clues with which to explore the precise etiology and mechanism underlying cryptorchidism and cryptorchidism-induced human infertility. Keywords: Arachidonic acid pathway, Bioinformatics, Cryptorchidism, Differentially expressed genes, GPX8, mTOR, RITOR, Spermatogenic

As the most abundantly used phthalate derivative, di-(2-ethylhexyl) phthalate (DEHP) leads to reproductive disorders, especially in males. Testicular injury can be triggered when the testis is exposed to DEHP during the immature stage. However, the potential mechanism is largely unclear. In the present study, Sprague-Dawley rats were exposed to 0, 250 and 500 mg/kg/day DEHP from postnatal day (PND) 20 to PND 30. The spermatogonia cell line GC-1 and spermatocyte cell line GC-2 were exposed to different doses of monoethylhexyl phthalate (MEHP), a metabolite of DEHP. Testicular injury was observed. Oxidative stress was evaluated both in vivo and in vitro. Our results showed that after DEHP exposure, the testicular structure was damaged and spermatogenesis was disturbed. We also found that oxidative stress was increased, as indicated by the upregulation of the important factors in the antioxidant pathway. Furthermore, the expression of autophagy-related proteins was significantly downregulated. Autophagy inhibition led to activation of the pyroptosis pathway. Nucleotide-binding and oligomerisation (NOD) domain-like receptor (NLR) family pyrin domain (PYD)-containing 3 (NLRP3), Caspase-1 and cytokine interleukin-1β (IL-1β) were significantly upregulated. Additionally, an imbalance in self-renewal and differentiation was observed in germ cells after DEHP exposure, causing the cessation of germ cell development. In summary, these data suggest that DEHP exposure enhances oxidative stress, downregulates autophagy, induces NLRP3 inflammasome activation and subsequently triggers pyroptosis in vivo and in vitro, which provides novel insight into DEHP-related injury in immature testes in the context of pyroptosis.

Study region: The Kaidu River Basin (KRB) is located on the central southern slope of the Tianshan Mountain in Northwest China. Study focus: This work aimed to assess changes and main drivers of snowmelt-driven runoff in KRB associated with three future climate scenarios. Six versions of the ''Cemaneige'' snowmelt module embedded in the hydrological model ''GR4J'' were calibrated and evaluated. The bias-corrected climate datasets from CMIP5 Models were used to drive the optimal snowmelt-hydrological model for runoff prediction. The factors that lead to runoff variations were also assessed. New hydrological insights: The significant declining trends of runoff were only predicted in the RCP4.5 and RCP8.5 scenarios. The declining trends of runoff were found in all the seasons. For the annual and summer runoff, compared to the historical period, both the RCP2.6 and RCP 4.5 periods showed a decline in the mid-century and a rise in the end-century; however, RCP8.5 showed a continuous decline during this period. Precipitation and evapotranspiration were ranked as the two most important factors regulating future runoff variations in all RCPs. In contrast, snowmelt timing is the second factor in the historical period, and its importance decreases in the warmer RCP scenarios. These results highlighted that the importance of snowmelt and snowmelt timing to the future runoff depends on the runoff responses to the trajectory of future changes in temperature and precipitation.

Background: Neurogenic bladder (NB) patients exhibit varying degrees of bladder fibrosis, and the thickening and hardening of the bladder wall induced by fibrosis will further affect bladder function and cause renal failure. Our study aimed to investigate the mechanism of bladder fibrosis caused by a spinal cord injury (SCI). Methods: NB rat models were created by cutting the bilateral lumbar 6 (L6) and sacral 1 (S1) spinal nerves. RNA-seq, Western blotting, immunofluorescence, cell viability and ELISA were performed to assess the inflammation and fibrosis levels. Results: The rats showed bladder dysfunction, upper urinary tract damage and bladder fibrosis after SCI. RNA-seq results indicated that hypoxia, EMT and pyroptosis might be involved in bladder fibrosis induced by SCI. Subsequent Western blot, ELISA and cell viability assays and immunofluorescence of bladder tissue confirmed the RNA-seq findings. Hypoxic exposure increased the expression of HIF-1α and induced EMT and pyroptosis in bladder epithelial cells. Furthermore, HIF-1α knockdown rescued hypoxia-induced pyroptosis, EMT and fibrosis. Conclusion: EMT and pyroptosis were involved in the development of SCI-induced bladder fibrosis via the HIF-1α pathway. Inhibition of the HIF-1α pathway may serve as a potential target to alleviate bladder fibrosis caused by SCI.

Renal fibrosis is a common pathological feature of various kidney diseases, leading to irreversible renal failure and end-stage renal disease. However, there are still no effective treatments to reverse renal fibrosis. This study aimed to explore the potential mechanism of a targeted drug for fibrosis. Here, unilateral ureteral obstruction (UUO)-treated mice and a TGF-β1-treated human renal tubular epithelial cell line (HK-2 cells) were used as models of renal fibrosis. Based on the changes of mRNA in UUO kidneys detected by transcriptome sequencing, MK-2206, an Akt inhibitor, was predicted as a potential drug to alleviate renal fibrosis through bioinformatics. We dissolved UUO mice with MK-2206 by gastric gavage and cultured TGF-β-induced HK-2 cells with MK-2206. Histopathological examinations were performed after MK-2206 intervention, and the degree of renal fibrosis, as well as the expression of Akt/mTOR pathway-related proteins, were evaluated by immunohistochemical staining, immunofluorescence staining, and Western blot. The results showed that MK-2206 significantly improved the pathological structure of the kidney. Furthermore, MK-2206 intervention effectively inhibited UUO- and TGF-β1-induced epithelial-mesenchymal transition, fibroblast activation, and extracellular matrix deposition. Mechanistically, MK-2206 treatment attenuated the activation of the Akt/mTOR signaling pathway. Taken together, our study revealed for the first time that MK-2206 is a promising drug for the improvement of renal fibrosis.

Di-(2-ethylhexyl) phthalate (DEHP) is the most common phthalate that can affect the male reproductive system. DEHP exposure at the prepubertal stage could lead to the injury of immature testes, but the mechanism has not been fully clarified. In the present study, we elucidated the possible underlying mechanism of DEHP-induced prepubertal testicular injury through stereological analysis and transcriptome profiling. Compared with the control group, the DEHP-treated rats had lower body weight gain and decreased testicular weight and organ coefficient. Moreover, lower serum levels of testosterone and LH were observed in the DEHP group, in contrast to the increased FSH level. Additionally, the serum level of estradiol had no significant difference after DEHP exposure. Stereological analysis showed significant reduction in volumes of most testicular structures, especially in the seminiferous tubule and seminiferous epithelium, along with a vast decrease of spermatogenic cells and obvious structural damages with substantial pathological signs (germ cracks, cytoplasmic vacuolization, sloughing, multinucleated giant cell formation, chromatolysis desquamation and dissolution, pyknosis of nuclei) in the seminiferous tubule upon DEHP exposure at the prepubertal stage. Furthermore, transcriptome profiling identified 5548 differentially expressed genes (DEGs) upon DEHP exposure. Pathway enrichment analysis revealed several crucial signaling pathways related to retinol metabolism, oxidative phosphorylation, steroid hormone biosynthesis, and cell adhesion molecules (CAMs). In addition, seven DEGs selected from RNA-seq data were validated by quantitative real-time polymerase chain reaction (qRT-PCR), and the results showed the same trends as the RNA-seq results. In conclusion, the above findings provide basic morphological data and lay a foundation for systematic research on transcriptome profiling in prepubertal testicular injury induced by DEHP.

Objective: Wilms tumor (WT) is a common malignant solid tumor in children. Many tumor biomarkers have been reported; however, there are poorly targetable molecular mechanisms which have been defined in WT. This study aimed to identify the oncogene in WT and explore the potential mechanisms.Methods: Differentially expressed genes (DEGs) in three independent RNA-seq datasets were downloaded from The Cancer Genome Atlas data portal and the Gene Expression Omnibus database (GSE66405 and GSE73209). The common DEGs were then subjected to Gene Ontology enrichment analysis, protein–protein interaction (PPI) network analysis, and gene set enrichment analysis. The protein expression levels of the hub gene were analyzed by immunohistochemical analysis and Western blotting in a 60 WT sample. The univariate Kaplan–Meier analysis for overall survival was performed, and the log-rank test was utilized. A small interfering RNA targeting cell division cycle 20 (CDC20) was transfected into G401 and SK-NEP-1 cell lines. The Cell Counting Kit-8 assay and wound healing assay were used to observe the changes in cell proliferation and migration after transfection. Flow cytometry was used to detect the effect on the cell cycle. Western blot was conducted to study the changes of related functional proteins.Results: We commonly identified 44 upregulation and 272 downregulation differentially expressed genes in three independent RNA-seq datasets. Gene and pathway enrichment analyses of the regulatory networks involving hub genes suggested that cell cycle changes are crucial in WT. The top 15 highly connected genes were found by PPI network analysis. Furthermore, we demonstrated that one candidate biomarker, CDC20, for the diagnosis of WT was detected, and its high expression predicted poor prognosis of WT patients. Moreover, the area under the curve value obtained by receiver operating characteristic curve analysis from paired WT samples was 0.9181. Finally, we found that the suppression of CDC20 inhibited proliferation and migration and resulted in G2/M phase arrest in WT cells. The mechanism may be involved in increasing the protein level of securin, cyclin B1, and cyclin AConclusion: Our results suggest that CDC20 could serve as a candidate diagnostic and prognostic biomarker for WT, and suppression of CDC20 may be a potential approach for the prevention and treatment of WT.

Radiation effect test cannot be performed in large-scale space simulations of a strong field electromagnetic environment, and existing BCI (bulk current injection) technology employed for nonlinear system tests is subjected to its limitation. Given this, the present study analyzes the equivalent radiation test method of BCI in the parallel double-line coupling channel. To be specific, the response analysis models of the EUT (equipment under test) under the radiation condition and the injection condition are developed with the nonlinear response system as the EUT. In addition, the corresponding equivalent relationship is derived between the voltage of the injection excitation source and the radiation field intensity. Subsequently, the condition and the test method to substitute BCI for radiation are proposed and experimentally verified. As revealed from the research results, specific to nonlinear response systems, the BCI method proposed here can be accurately equated with the radiation effect test of the EUT. It is noteworthy that the maximum test error only reaches 3.62 dB, capable of satisfying the actual requirements of the project.

In order to make certain of the blocking impact of the ultra-wideband electromagnetic pulse (UWB EMP) on a radio communication station, an EMP injection test was conducted to study the blocking interference of a digital radio station under a step pulse train and double exponential pulse train. Combined with waveform parameters such as the pulse repetition rate (PRR), the concept of influence time when the UWB EMP was irradiated on the equipment under test (EUT) was introduced, and the model was established. According to the experimental results, the blocking impact of the EUT under the UWB EMP depended on factors such as waveform, PRR, and amplitude. The relationship between the PRR and the sensitive bit error rate could be determined by the effect test. In the case of a low PRR, the sensitive voltage threshold of the EUT was irrelevant to the PRR, and the effect was the monopulse effect. When the PRR reached above the reciprocal of the influence time, the sensitive voltage threshold of the EUT decreased with the increase in the PRR, which conformed to the cumulative multiple pulse effects.

Abstract Background It has been recognized that the incidence of prostatic utricle in boys is increasing and is closely associated with diseases such as hypospadias. However, the clinical features of prostatic utricle with normal external genitalia have received little attention. Methods Based on this, a series of 22 male children with prostatic utricles has been compiled by adding our 3 patients to 19 cases reported. All children enrolled had normal external genitalia. Clinical data of the case was reviewed. Results Urinary tract infection, purulent urethral discharge and pyuria were the most common presenting chief complaint (41%), irritative lower urinary tract symptoms were present in 17% of cases, obstructive lower urinary tract symptoms were noted in 14%. Urinary retention has been reported in 18% and epididymitis has been reported in 14%. Relatively rare clinical symptoms are abdominal pain, hematuria, and hematospermia. A case of calculus formation and a case of neoplasia within the prostatic utricle has been reported. A cystic mass found by digital rectal examination is the most common presenting sign. A utricular lesion posterior to the bladder was revealed by imaging examination. Unilateral renal agenesis was associated in 32% of reports. Non-surgical approach was chosen in 3 cases, transrectal ultrasonography guided aspiration has been reported in 1 case. Endoscopic techniques were used in 3 cases. Open excision was used in 11 cases. The laparoscopic excision was chosen in 3 cases and Robot-assisted laparoscopy was reported in 1 case. Symptoms and signs disappeared after treatment in all children, and no recurrence occurred during follow-up. Conclusions Prostate utricles without external genital anomalies are rarely reported in children, and are easily missed and misdiagnosed, often accompanied by recurrent urinary tract infections, lower urinary tract symptoms, epididymitis, dysuria and other symptoms. Imaging studies can confirm the diagnosis. Symptomatic and large utricles should be actively treated. The treatment program should be based on the age, clinical symptoms, and size and location of the utricle.

In order to master the position variation rule of radar false alarm signal under continuous wave (CW) electromagnetic interference and reveal the mechanism of CW on radar, taking a certain type of stepping frequency radar as the research object, theoretical analysis of the imaging mechanism of radar CW electromagnetic interference false alarm signals from the perspective of time-frequency decoupling and receiver signal processing. Secondly, electromagnetic interference injection method is used to test the single-frequency and dual-frequency electromagnetic interference effect of the tested equipment. The results show that under the single frequency CW electromagnetic interference, the sensitive bandwidth of false alarm signal is about ±75 MHz, and the position of false alarm signal irregularity changes. Under the in-band dual-frequency CW electromagnetic interference, the position of non-intermodulation false alarm signal is similar to that of single frequency. However, the distance difference of two non-intermodulation false alarm signals is regular. In addition, the positions of the second-order intermodulation false alarm signals of the tested radar are also regular, and its position changes with the change of the second-order intermodulation frequency difference.

Most studies assessing the safety of hot bridge wire EEDs employ temperature sensors that directly use the measurements of the temperature measurement device without analyzing the accuracy of the temperature measurement. This study establishes the response function of the exposed bridge and exposed bridge temperature rise system of hot bridge wire EEDs through the Rosenthal’s temperature rise equation and Laplace transformation as well as experimental tests, and through the response function, the response law and numerical characteristics of the two are compared and analyzed under four typical excitations. Under steady current injection and continuous-wave radiation, both exposed bridge and exposed bridge temperature measurement systems can reach thermal equilibrium, and the equilibrium temperature of both are the same. However, under pulse excitation, the temperature rise measurement value is significantly different from the actual value due to the large difference in response time of the exposed bridge (1 ms) and the exposed bridge temperature measurement device (0.82 s). Studies have shown that under steady current injection and continuous-wave radiation, temperature rise measurements can be directly applied to the safety assessment of hot bridge wire EEDs, while under pulsed conditions, temperature rise measurements cannot be directly applied.

Abstract Background Autologous urothelial cells are often obtained via bladder biopsy to generate the bio-engineered urethra or bladder, while urine-derived stem cells (USC) can be obtained by a non-invasive approach. The objective of this study is to develop an optimal strategy for urothelium with permeability barrier properties using human USC which could be used for tissue repair in the urinary tract system. Methods USC were harvested from six healthy adult individuals. To optimize urothelial differentiation, five different differentiation methods were studied. The induced cells were assessed for gene and protein expression markers of urothelial cells via RT-PCR, Western blotting, and immunofluorescent staining. Barrier function and ultrastructure of the tight junction were assessed with permeability assays and transmission electron microscopy (TEM). Induced cells were both cultured on trans-well membranes and small intestinal submucosa, then investigated under histology analysis. Results Differentiated USC expressed significantly higher levels of urothelial-specific transcripts and proteins (Uroplakin III and Ia), epithelial cell markers (CK20 and AE1/AE3), and tight junction markers (ZO-1, ZO-2, E-cadherin, and Cingulin) in a time-dependent manner, compared to non-induced USC. In vitro assays using fluorescent dye demonstrated a significant reduction in permeability of differentiated USC. In addition, transmission electron microscopy confirmed appropriate ultrastructure of urothelium differentiated from USC, including tight junction formation between neighboring cells, which was similar to positive controls. Furthermore, multilayered urothelial tissues formed 2 weeks after USC were differentiated on intestine submucosal matrix. Conclusion The present study illustrates an optimal strategy for the generation of differentiated urothelium from stem cells isolated from the urine. The induced urothelium is phenotypically and functionally like native urothelium and has proposed uses in in vivo urological tissue repair or in vitro urethra or bladder modeling.

Di-(2-ethylhexyl) phthalate (DEHP), one of the most commonly used endocrine-disrupting chemicals, has been shown to cause reproductive dysfunction in humans and animal models. However, very few studies have investigated the impact of DEHP at the post-transcriptional level in mouse testes, and the underlying mechanisms remain unclear. In the present research, TM3 Leydig cells were treated with 200 µM phthalic acid mono-2-ethylhexyl ester (MEHP, bio-metabolite of DEHP), and then the mRNA and lncRNA sequencing of TM3 Leydig cells was performed. Mice were exposed prepubertally to 0 or 500 mg DEHP/kg/day. RNA sequencing of mouse testes was performed to verify the RNA-seq results in vitro. The expression patterns of relevant genes and proteins were verified using real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting. DEHP and MEHP exposure led to testicular damage and accelerated cell aging via ROS accumulation. RNA sequencing analyses indicated that FOXO signaling and longevity regulation pathways were activated in resistance to ROS accumulation. FOXO signaling and longevity regulation pathway-related genes and proteins were also activated. By constructing a competing endogenous RNA (ceRNA) network, we observed that the ceRNA network might play a role in regulating FOXO signaling and longevity regulation pathways in response to excessive ROS accumulation and cell aging. In summary, our data here suggests that the ceRNA network may play a role in regulating FOXO signaling and longevity pathways in response to DEHP exposure in mouse testes.

The present study proposed the equivalent test method for the strong electromagnetic field radiation of electric explosive devices (EEDs) of the weapon equipment to satisfy the military requirements of the electromagnetic radiation safety test, as well as the evaluation of the electric ignition, the electric initiation ammunition, or missiles. Under stable conditions, the ignition excitation test and the bridge wire temperature increase test were performed to determine the ignition temperature of the EED. As radiated by the strong electromagnetic field, the relationship between the temperature increase of the bridge wire and the electric field intensity of the EED was developed based on the theoretical analysis and the experimental test. Given the ignition temperature of the EED, the radiation field intensity of the EED at 50% ignition was determined. As compared with the 50% ignition field intensity of the EED directly radiated by the strong electromagnetic field, an error less than 1 dB was caused. On that basis, the correctness of the equivalent test method was verified. Accordingly, this method was suggested to act as an effective method and technical means to test and evaluate the electromagnetic radiation safety of ammunition and missiles in unfavorable electromagnetic environments.

Purpose: The aim of this study was to systematically review the literature on the complications and postoperative outcomes of children with non-proximal hypospadias.Methods: Electronic databases including PubMed, Embase, and Cochrane Library CENTRAL were searched systematically from January 1990 to June 2020 for the literature that reported the postoperative outcomes of patients with non-proximal hypospadias. Non-proximal hypospadias encompassed distal and mid-penile hypospadias.Results: We included 44 studies involving 10,666 subjects. Urethrocutaneous fistula (UCF) was the most common complication with an incidence of 4.0% (95% CI, 3.1–5.0%). Incidence of overall complications was 8.0% (95% CI, 6.3–9.8%). Meta-regression analysis revealed that length of urethral stent indwelling (coefficient 0.006; 95% CI, 0.000–0.011; p = 0.036) and penile dressing (coefficient 0.010; 95% CI, 0.000–0.021; p = 0.048) were two risk factors for UCF. Multivariate meta-regression analysis did not identify any independent risk factors for UCF. No differences were found between stent and stentless groups in non-proximal hypospadias regarding incidences of UCF (OR, 0.589; 95% CI, 0.267–1.297), meatal stenosis (OR, 0.880; 95% CI, 0.318–2.437), and overall complications (OR, 0.695; 95% CI, 0.403–1.199). No differences were found between foreskin preservation and circumcision in terms of complications either.Conclusions: UCF is the most common complication following hypospadias repair with an incidence of 4.0%. Independent risk factors for UCF were not identified in the current research. Distal hypospadias repair without stent indwelling is not likely to compromise the postoperative outcome. Further studies should be designed to explore the differences between different surgical approaches and the potential risk factors for complications following hypospadias repair.

Introduction: Extracorporeal membrane oxygenation (ECMO) has been widely used to treat cardiopulmonary failure in patients with congenital heart defects (CHD) postoperatively. A meta-analysis is performed for outcomes of postoperative CHD patients on ECMO.Methods: Electronic databases, including PubMed, EMbase, and Cochrane Library CENTRAL were searched systematically from January 1990 to June 2020 for literature which reported the outcomes of postoperative CHD cases on ECMO. The scope of this search was restricted to articles published in English.Results: Forty-three studies were included in this study, involving 3,585 subjects. Postoperative ventricular failure with low cardiac output was the most common indication of ECMO initiation. The pooled estimated incidence of in-hospital mortality was 56.8% (95% CI, 52.5–61.0%). Bleeding was the most common complication with ECMO with an incidence of 47.1% (95% CI, 38.5–55.8%). Multivariate meta-regression analysis revealed that single ventricular physiology (coefficient 0.213, 95% CI 0.099–0.327, P = 0.001) and renal failure (coefficient 0.315, 95% CI 0.091–0.540, P = 0.008) were two independent risk factors for in-hospital mortality.Conclusions: There is an overall high in-hospital mortality of 56.8% in postoperative CHD patients on ECMO. Bleeding is the most common complication during ECMO running with an incidence of 47.1%. Single ventricular physiology and renal failure, as two independent risk factors, may potentially increase in-hospital mortality. Further studies exploring the differences in outcomes between ECMO and other extracorporeal life support strategies are warranted.

Background: MicroRNA-155-5p (miR-155-5p) has been reported to play an oncogenic role in different human malignancies; however, its role in Wilms tumor (WT) remains unclear. Methods: Differentially expressed miRNAs (DE-miRNAs) and mRNAs (DEGs) in WT blood and tissues were identified by using miRNA microarray and RNA-sequencing. Bioinformatics prediction and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to predict the potential functions of DE-miRNAs. DE-miRNAs and DEGs in WT obtained from Gene Expression Omnibus (GEO) and Therapeutically Applicable Research to Generate Effective Treatments (TARGET) were identified by using the “edgeR” package. RT-qPCR was used to explore miR-155-5p and IGF2 expression and their clinical significance in WT specimens. A rhabdoid cell line (G401) and Ewing sarcoma cell line (SK-NEP-1) were used. Immunohistochemical staining, western blotting and dual-luciferase reporter assays were performed to study the mechanisms involved. The CCK-8, flow cytometry, wound healing and transwell assays were performed to identify the effects of miR-155-5p and IGF2 knockdown on cell proliferation, apoptosis, migration and invasion, respectively. Results: MiR-155-5p was downregulated in both blood and tissues from WT patients who did not receive chemotherapy before surgery but was upregulated in tissues from WT patients who had received chemotherapy before surgery. IGF2, PI3K, AKT and mTOR were found to be upregulated in WT tissues. Additionally, miR-155-5p and IGF2 were significantly correlated with TNM stage and lymphatic metastasis in WT patients. Molecular mechanism exploration indicated that IGF2 was downregulated by miR-155-5p via direct binding to its 3’ untranslated region in cell lines. Furthermore, IGF2, PI3K, AKT and mTOR expression was inversely correlated with miR-155-5p expression, and PI3K, AKT and mTOR expression was positively correlated with IGF2 expression in cell culture. Functional studies demonstrated that miR-155-5p upregulation and IGF2 knockdown suppressed cell proliferation, migration and invasion and induced cell apoptosis. Moreover, the tumor-suppressing effects of miR-155-5p in cells were abrogated by miR-155-5p inhibitor treatment. Conclusions: Taken together, these findings suggest that miR-155-5p functions as a tumor suppressor in WT through inactivating the PI3K/AKT/mTOR signaling pathway by directly targeting IGF2. Thus, miR-155-5p might be a novel therapeutic target for WT.

Two hypotheses for the blocking effect mechanisms under the electromagnetic radiation are presented, and the corresponding dual-frequency interference prediction models are proposed, which can be used to predict the working state of equipment under the condition that the single-frequency susceptibility is known. By taking a radar and a communication radio as the EUT, the experiments of dual-frequency continuous wave electromagnetic radiation are designed and carried out to verify the prediction models. The test results show that the sensitive bandwidth of blocking interference effect for the tested radar and the communication station is consistent with their working bandwidth, respectively. By substituting the test data into the proposed prediction models, the prediction errors of the models are less than 13%. Moreover, it can be found that the tested radar is more sensitive to the peak value of electric field, and the tested communication station is more sensitive to the effective value of electric field.

Abstract Background Renal fibrosis is characterized by infiltration of interstitial inflammatory cells and release of inflammatory mediators, activation and proliferation of fibroblasts, and deposition of excessive extracellular matrix (ECM). The aim of this study was to evaluate the effect of human umbilical cord-derived mesenchymal stem cell (hucMSC) conditioned medium (CM) on renal tubulointerstitial inflammation and fibrosis. Methods Renal interstitial fibrosis was prepared in vivo using the unilateral ureteral obstruction (UUO). Rats were divided randomly into Sham group, Sham group with CM, UUO group, and UUO group with CM. The effect of hucMSC-CM on kidney injury induced by UUO was assessed by detecting kidney histopathology, serum creatinine (SCr), and blood urea nitrogen (BUN). The levels of TNF-α, IL-6, and IL-1β in serum and kidney tissues were detected by ELISA. The expression of proteins associated with fibrosis and renal inflammation was investigated using immunohistochemical staining and western blotting. The effects of hucMSC-CM on the TGF-β1-induced epithelial–mesenchymal transition (EMT) process and on inflammation in NRK-52E cells were investigated by immunofluorescent staining, ELISA, and western blotting. Results hucMSC-CM reduced extracellular matrix deposition and inflammatory cell infiltration as well as release of inflammatory factors in UUO-induced renal fibrosis. Furthermore, hucMSC-CM markedly attenuated the EMT process and proinflammatory cytokines in rats with UUO and TGF-β1-induced NRK-52E cells. hucMSC-CM also inhibited the TLR4/NF-κB signaling pathway in vivo and in vitro. Conclusions Our results suggest that hucMSC-CM has protective effects against UUO-induced renal fibrosis and that hucMSC-CM exhibits its anti-inflammatory effects through inhibiting TLR4/NF-κB signaling pathway activation.

To objectively assess the anti-electromagnetic interference ability of the navigation receiver, the sensitivity criterion of a certain type of navigation receiver is tested under single-frequency continuous wave electromagnetic radiation with an optimized testing method. The experimental results show that it is difficult to guarantee the accuracy of the measurement value of the sensitivity level by using the carrier-to-noise density ratio (C/N0) as the sensitivity criterion, but the initial C/N0 of each satellite can be used as the basis for identifying whether the navigation system has recovered from the interference. The experimental error is dramatically decreased when the sensitivity criterion of “the sensitive phenomenon appears within the first 4 s, and the loss of positioning lasts for 30 s” is employed, the variable interference power step size is adopted and all of the satellites C/N0 are required to recover to the initial value after an interference. The critical interference field intensity error can be controlled within 1 dB by using all these measures. The sensitivity law of the navigation receiver is the same under different working signal intensities. It is significantly sensitive in the working frequency bandwidth. It is also quite sensitive in −11.5 MHz~55.5 MHz of the frequency offset range. The positive sensitive bandwidth is about 5 times that of the negative sensitive bandwidth.