Does bilateral Wilms' tumor involving the collecting system in children have a worse prognosis?

BACKGROUND: The literature on nephron-sparing surgery (NSS) in children with bilateral Wilms' tumors (BWT) involving the collection system is mostly comprised of case reports. The present study aimed to summarize the clinical characteristics, treatments, and prognosis of children with BWT involving the collecting system admitted to our pediatric surgery center compared with those whose tumors did not involve the collecting system. A secondary aim was to discuss how to preserve more kidney parenchyma and prevent long-term renal failure under the premise of preventing tumor recurrence. METHODS: Patients with BWT admitted to our pediatric surgery center between January 2008 and June 2022 were reviewed. All included patients were grouped according to the relationship between the tumor and collecting system according to the intraoperative findings. Group I included children with tumor infiltrating the collecting system, group II included children with tumor growing into the collecting system, and group III included children whose tumor did not involve the collecting system. The clinical features, treatments and prognosis of the patients were analyzed. RESULTS: Seventy patients were enrolled, including 20 patients with 25 sides of tumors infiltrating the collecting system in group I,10 patients with 13 sides of tumors growing into the collecting system in group II, and 40 patients in group III. There was no significant difference in patients age and gender between group I and group II. In total, 20 patients in group I and 9 patients in group II had partial response (PR) after neoadjuvant chemotherapy. In group I, 22 of 25 sides of tumors underwent NSS; in group II, 11 of 13 sides of tumors underwent NSS. During an average follow-up of 47 months, in group I, 6/20 patients relapsed and 2/20 patients died; in group II, 3/10 patients relapsed and 1/10 patient died. There was no significant difference in 4-year overall survival (OS) rate among groups I, II and III (86.36% vs. 85.71%vs. 91.40%, P = 0.902). CONCLUSIONS: To preserve renal parenchyma, NSS is feasible for children with BWT involving the collecting system. There was no significant difference in postoperative long-term OS between patients with BWT involving the collecting system and not involving the collecting system.

Treatment of bilateral Wilms' tumor in children: how to improve the application of nephron-sparing surgery.

PURPOSE: To summarize the experience of nephron-sparing surgery (NSS) for bilateral Wilms tumors (BWT) in children. METHODS: This study included children with BWT admitted to our hospital between January 2008 and June 2022. The details of the treatments and outcomes were analyzed. RESULTS: In all, 70 patients (39 males and 31 females) were enrolled, including 66 patients with synchronous tumors and 4 patients with metachronous tumors. The median age at diagnosis was 13 (3-75) months. Overall, 59 patients received preoperative chemotherapy and 45.8% (54/118) of the 118 sides of WT achieved a partial response (PR). Of the 70 patients, 48 (68.6%) underwent bilateral NSS and 22 (31.4%) underwent unilateral NSS and contralateral total nephrectomy. The proportion of bilateral NSS in the preoperative chemotherapy group was significantly higher than in the non-chemotherapy group (P = 0.031). Additionally, there were 26, 25, 14, and 5 cases of stage I, stage II, stage III, and stage IV, respectively. Among the 70 children, 16 had a recurrence, and 8 died. The 4 years EFS and OS were 67.9% and 89.3%, respectively. CONCLUSIONS: The long-term survival rates of patients with BWT improved. Hence, preoperative chemotherapy should be administered to enhance the use of NSS in BWT.

Studying the mechanism of sperm DNA damage caused by folate deficiency.

Sperm DNA injury is one of the common causes of male infertility. Folic acid deficiency would increase the methylation level of the important genes, including those involved in DNA double-strand break (DSB) repair pathway. In the early stages, we analysed the correlation between seminal plasma folic acid concentration and semen parameters in 157 infertility patients and 91 sperm donor volunteers, and found that there was a significant negative correlation between seminal folic acid concentration and sperm DNA Fragmentation Index (DFI; r = -0.495, p < 0.01). Then through reduced representation bisulphite sequencing, global DNA methylation of sperm of patients in the low folic acid group and the high folic acid group was analysed, it was found that the methylation level in Rad54 promoter region increased in the folic acid deficiency group compared with the normal folic acid group. Meanwhile, the results of animal model and spermatocyte line (GC-2) also found that folic acid deficiency can increase the methylation level in Rad54 promoter region, increased sperm DFI in mice, increased the expression of γ-H2AX, that is, DNA injury marker protein, and increased sensitivity of GC-2 to external damage and stimulation. The study indicates that the expression of Rad54 is downregulated by folic acid deficiency via DNA methylation. This may be one of the mechanisms of sperm DNA damage caused by folate deficiency.

A multicenter study on surgical procedure selection and risk factor analysis of postoperative complications after TIP and Duckett hypospadias repair.

BACKGROUND: Hypospadias is a common congenital malformation in pediatric urology with surgery being the only curative treatment. Although there are hundreds of surgical methods for hypospadias, no single method can treat all types, and there are still high rates of postoperative complications. We performed this study to investigate surgical procedure selection and perform risk factor analysis of postoperative complications in hypospadias repair. METHODS: Retrospective analysis was performed of complete clinical and follow-up data of children with hypospadias who were treated and followed up at 15 children's clinical centers in Mainland China from December 2018 to December 2019. Children were divided into groups according to Barcat classification and surgical methods in order to analyze the surgical choice for different types of hypospadias and the influencing factors of different surgical methods for complications. RESULTS: In total, 1011 patients were followed up for 26 months. According to Barcat classification, there were 248 cases of distal type hypospadias, 214 of intermediate, and 549 of proximal type. Transverse preputial island flap urethroplasty (Duckett) and tubularized incised plate urethroplasty (TIP) were performed in 375 (37.1%) and 336 cases (33.2%), respectively. The postoperative complication rate of distal hypospadias was 23.4% (15.8-57.1%), mid shaft 29.0% (22.7-40.0%), and proximal 43.7% (30.2-52.9%). Among the 375 patients in Duckett group, 192 had complications. Multivariate logistic analysis showed that the length of prepuce island flap (OR = 3.506, 95% CI: 2.258-5.442) was an independent risk factor for complications after Duckett operation (P < 0.001). In TIP group, there were 336 cases with 84 complications. Multivariate logistic analysis showed that the width of urethral plate after longitudinal resection (OR = 0.836, 95% CI: 0.742-0.942) and glans width (OR = 0.851, 95% CI: 0.749-0.965) were independent risk factors for postoperative complications after TIP (P = 0.003, P = 0.012). CONCLUSION: Several anatomical features play a role during the selection process among the different surgical approaches, including glans size, urethral plate width, and the meatal position. The width of the urethral plate and glans width were risk factors for postoperative complications after TIP. The length of prepuce island flap was a risk factor for complications after Duckett operation.

Knowledge, attitude and application towards fast track surgery among operating room paramedics: a cross-sectional study.

BACKGROUND: Fast track surgery has shown its effectiveness to accelerate recovery and gained acceptance in many operations. However, data for paramedics using fast track surgery are limited in China. The aims of our study are to evaluate the knowledge, attitude and application status of fast track surgery in paramedics and to provide suggestions for the better application of fast track surgery. METHODS: Two Hundred Ninety-one operating room paramedics were investigated by simple random sampling from October 20 to December 20, 2019 time. A self-reported questionnaire was used to collect data with five dimensions: demographic data, cognitive level, knowledge, attitude and application of fast track surgery. Data were analyzed using qualitative and quantitative methods. RESULTS: 19.93% of participants never heard fast track surgery and only 3.32% of participants were very familiar with it. Gender (0.702, 95% CI 0.109-1.294), technical title (0.342, 95% CI 0.126-0.558) and awareness of the concept of fast track surgery (0.471, 95% CI 0.165-0.776) had a correlation with the knowledge level of paramedics towards fast track surgery. In terms of attitude towards fast track surgery, gender (- 1.944, 95% CI -3.830- -0.058), age (0.303, 95% CI 0.021-0.585) and knowledge score of fast track surgery (0.426, 95% CI 0.014-0.838) are related. Half of the paramedics believe the most difficult problem in the application of fast track surgery was the lack of multi-team communication and cooperation. CONCLUSION: The knowledge of fast track surgery among paramedics in Wuhan is poor, and some paramedics have a negative attitude towards it. As the attitude is positively correlated with the knowledge, it is necessary to improve the knowledge level of fast track surgery among paramedics in Wuhan.

[Association of phthalate and polycyclic aromatic hydrocarbon exposure during early pregnancy with premature delivery: A cohort study].

OBJECTIVE: To explore the relationship of the exposure to phthalate esters (PAE) and polycyclic aromatic hydrocarbons (PAH) with clinical premature delivery during early pregnancy. METHODS: We conducted a baseline questionnaire survey among 821 pregnant women undergoing prenatal examination in Hubei Provincial Maternal and Child Health Care Hospital, collected their morning urine samples and followed them up to the outcomes of pregnancy. We quantitatively analyzed 10 PAE and 10 PAH metabolites in the urine samples, followed by Mann-Whitney U test, chi-square test, and logistic regression analysis. RESULTS: The detection rate of the 5 factors exposed to was >80% while that of phthalic acid monobenzyl ester (MBzP) was <50% in PAEs; that of the 5 factors exposed to was >80%, that of 3-hydroxyphene (3-OHPHE) was 86.91% while that of 4-hydroxyphene (4-OHPHE) was <50% in PAHs. Logistic regression analysis showed that the risk of premature delivery was higher in the high MBzP- than in the low MBzP-exposure group (aOR = 2.26, 95% CI: 1.17－4.39). CONCLUSION: High MBzP-exposure may be a risk factor for premature delivery.

Cardiac developmental toxicity and transcriptome analyses of zebrafish (Danio rerio) embryos exposed to Mancozeb.

Mancozeb (MZ), an antibacterial pesticide, has been linked to reproductive toxicity, neurotoxicity, and endocrine disruption. However, whether MZ has cardiactoxicity is unclear. In this study, the cardiotoxic effects of exposure to environment-related MZ concentrations ranging from 1.88 µM to 7.52 µM were evaluated at the larval stage of zebrafish. Transcriptome sequencing predicted the mechanism of MZ-induced cardiac developmental toxicity in zebrafish by enrichment analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). Consistent with morphological changes, the osm, pfkfb3, foxh1, stc1, and nrarpb genes may effect normal development of zebrafish heart by activating NOTCH signaling pathways, resulting in pericardial edema, myocardial fibrosis, and congestion in the heart area. Moreover, differential gene expression analysis indicated that cyp-related genes (cyp1c2 and cyp3c3) were significantly upregulated after MZ treatment, which may be related to apoptosis of myocardial cells. These results were verified by real-time quantitative RT-qPCR and acridine orange staining. Our findings suggest that MZ-mediated cardiotoxic development of zebrafish larvae may be related to the activation of Notch and apoptosis-related signaling pathways.

Nanozyme-Based Pump-free Microfluidic Chip for Colorectal Cancer Diagnosis via Circulating Cancer Stem Cell Detection.

Circulating cancer stem cells (CCSCs) are subpopulations of cancer cells with high tumorigenicity, chemoresistance, and metastatic potential, which are also major drivers of disease progression. Herein, to achieve the prediction of tumor diagnosis and progression in colorectal cancer (CRC), a new, automated, and portable lateral displacement patterned pump-free (LP) microfluidic chip (LP-chip) with the CoPt3 nanozyme was established for CCSC capture and detection in peripheral blood and feces samples ex vivo. In this design, CoPt3@HA probes with functions of magnetic separation and colorimetric signal transduction by peroxidase-mimicking activity were applied for the capture of CCSCs and signal output in clinical samples. The generated colors of polydopamine (PDA) were quantifiable through the smartphone APP and visualizable by the naked eye in the test line (T line) and control line (C line) of the LP-chip. In the optimal experimental conditions, the CCSC concentration was sensitive to change in the range 0-105 cells mL-1, with a detection limit of 3 cells mL-1 (S/N = 3). Preliminary studies of clinical samples suggest that the platform has the potential for prediction of colorectal cancer progression and poor prognosis. Overall, the LP-chip provides potential strategies for timely diagnosis, therapeutic monitoring, and recurrence prediction to improve home-based patient care.

Carbon dot-based fluorescent probe for early diagnosis of pheochromocytoma through identification of circulating tumor cells.

Pheochromocytoma (PCC), as a rare neuroendocrine tumor, is often missed or misdiagnosed because of its atypical clinical manifestations. To realize the early accurate diagnosis of PCC, we have selected circulating tumor cells (CTCs) with more complete biological information as biomarkers and developed a simple and novel fluorescence cytosensor. Octreotide-2,2',2'',2'''- (1,4,7,10 -tetraazacyclododecane-1,4,7,10-tetrayl) tetraacetic acid (DOTA) modified magnetic Fe3O4 and signal amplification CDs@SiO2 nanospheres are prepared to capture and detect PCC-CTCs from peripheral blood via binding to the somatostatin receptor SSTR2 overexpressed on the surface of PCC cells. During the detection process, the target cells were separated and enriched by magnetic capture probes (Fe3O4-DOTA), and then signal probes (CDs@SiO2-DOTA) could also specifically bound to target cells to form the sandwich-like structure for fluorescence signal output. The proposed fluorescence cytosensor has revealed good sensitivity and selectivity for quantitative analysis of PCC-CTCs in the concentration of 5-1000 cells mL-1 with a LOD of 2 cells mL-1. More importantly, designed fluorescence cytosensor has shown good reliability and stability in complex serum samples. This strategy provides a new way for detection of PCC-CTCs.

The combination of deep learning and pseudo-MS image improves the applicability of metabolomics to congenital heart defect prenatal screening.

To investigate the metabolic alterations in maternal individuals with fetal congenital heart disease (FCHD), establish the FCHD diagnostic models, and assess the performance of these models, we recruited two batches of pregnant women. By metabolomics analysis using Ultra High-performance Liquid Chromatography-Mass/Mass (UPLC-MS/MS), a total of 36 significantly altered metabolites (VIP >1.0) were identified between FCHD and non-FCHD groups. Two logistic regression models and four support vector machine (SVM) models exhibited strong performance and clinical utility in the training set (area under the curve (AUC) = 1.00). The convolutional neural network (CNN) model also demonstrated commendable performance and clinical utility (AUC = 0.89 in the training set). Notably, in the validation set, the performance of the CNN model (AUC = 0.66, precision = 0.714) exhibited better robustness than the six models above (AUC≤0.50). In conclusion, the CNN model based on pseudo-MS images holds promise for real-world and clinical applications due to its better repeatability.

Cascaded nanozyme-based high-throughput microfluidic device integrating with glucometer and smartphone for point-of-care pheochromocytoma diagnosis.

The development of point-of-care (POC) diagnostics devices for circulating tumor cells (CTCs) detection plays an important role in the early diagnosis of pheochromocytoma (PCC), especially in a low-resource setting. To further realize the rapid, portable, and high-throughput detection of CTCs, an Au@CuMOF cascade enzyme-based microfluidic device for instant point-of-care detection of CTCs was constructed by combining a smartphone application and a commercial portable glucose meter (PGM). In this microfluidic system, DOTA and norepinephrine (NE) modified Au@CuMOF signal probes and Fe3O4@SiO2 capture probes were used for the dual recognition and capture of rare PCC-CTCs. Then, the targeted binding of the Au@CuMOF cascade nanozymes to the CTCs endowed the cellular complexes with multienzyme mimetic activities (i.e., glucose oxidase-like and peroxidase-like activity) to catalyze glucose reduction as signal output for colorimetric and personal glucose meter (PGM) dual-mode detection of CTCs. The developed method has a linear range of 4 to 105 cells mL-1 and a detection limit of 3 cells mL-1. This method allows the simultaneous detection of six samples and demonstrates good applicability for CTCs detection in whole blood samples. More importantly, the combination of PGM, smartphone app and array microfluidic chips enables the rapid, portable, and high-throughput diagnoses of PCC, and providing provide a convenient and reliable alternative to traditional liquid biopsy diagnosis of various cancers.

Prenatal exposure to polycyclic aromatic hydrocarbons and phthalate acid esters and gestational diabetes mellitus: A prospective cohort study.

BACKGROUND: Polycyclic aromatic hydrocarbons and phthalate acid esters (PAHs & PAEs), known as endocrine disrupting chemicals (EDCs), widely exist in daily life and industrial production. Previous studies have suggested that PAHs & PAEs may modify the intrauterine homeostasis and have adverse effects on fetal development. However, epidemiological evidence on the associations between PAHs & PAEs and gestational diabetes mellitus (GDM) is still limited. OBJECTIVE: To investigate the effects of prenatal PAHs &PAEs exposure on the risk of GDM and hyperglycemia in pregnant women. METHODS: The study population was a total of 725 pregnant women from a prospective birth cohort study conducted from December 2019 to December 2021. Blood glucose levels were collected by the hospital information system. Urinary PAHs & PAEs concentrations were determined by gas chromatography tandem mass spectrometry. The Poisson regression in a generalized linear model (GLM), multiple linear regression, quantile-based g-computation method (qgcomp), and Bayesian kernel machine regression (BKMR) were applied to explore and verify the individual and overall effects of PAHs & PAEs on glucose homeostasis. Potential confounders were adjusted in all statistical models. RESULTS: A total of 179 (24.69%) women were diagnosed with GDM. The Poisson regression suggested that a ln-unit increment of 4-OHPHE (4-hydroxyphenanthrene) (adjusted Risk Ratio (aRR) = 1.13; 1.02-1.26) was associated with the increased GDM risk. Mixed-exposure models showed similar results. We additionally found that MBZP (mono-benzyl phthalate) (aRR = 1.19; 1.02-1.39) was positively related to GDM risk in qgcomp model. Although neither model demonstrated that 2-OHNAP (2-hydroxynaphthalene) and 9-OHFLU (9-hydroxyfluorene) increased the risk of GDM, 2-OHNAP and 9-OHFLU exposure significantly increased blood glucose levels. BKMR model further confirmed that overall effects of PAHs & PAEs were significantly associated with the gestational hyperglycemia and GDM risk. CONCLUSIONS: Our study presents that environmental exposure to PAHs & PAEs was positively associated with gestational glucose levels and the risks of developing GDM. In particular, 2-OHNAP, 9-OHFLU, 4-OHPHE and MBZP may serve as important surveillance markers to prevent the development of GDM.

Adverse impact of phthalate and polycyclic aromatic hydrocarbon mixtures on birth outcomes: A metabolome Exposome-Wide association study.

It has been well-investigating that individual phthalates (PAEs) or polycyclic aromatic hydrocarbons (PAHs) affect public health. However, there is still a gap that the mixture of PAEs and PAHs impacts birth outcomes. Through innovative methods for mixtures in epidemiology, we used a metabolome Exposome-Wide Association Study (mExWAS) to evaluate and explain the association between exposure to PAEs and PAHs mixtures and birth outcomes. Exposure to a higher level of PAEs and PAHs mixture was associated with lower birth weight (maximum cumulative effect: 143.5 g) rather than gestational age. Mono(2-ethlyhexyl) phthalate (MEHP) (posterior inclusion probability, PIP = 0.51), 9-hydroxyphenanthrene (9-OHPHE) (PIP = 0.53), and 1-hydroxypyrene (1-OHPYR) (PIP = 0.28) were identified as the most important compounds in the mixture. In mExWAS, we successfully annotated four overlapping metabolites associated with both MEHP/9-OHPHE/1-OHPYR and birth weight, including arginine, stearamide, Arg-Gln, and valine. Moreover, several lipid-related metabolism pathways, including fatty acid biosynthesis and degradation, alpha-linolenic acid, and linoleic acid metabolism, were disturbed. In summary, these findings may provide new insights into the underlying mechanisms by which PAE and PAHs affect fetal growth.

Seminal plasma S100A8/A9 as a potential biomarker of genital tract inflammation.

ABSTRACT: Infections and inflammatory reactions in the male genital tract are the leading causes of male infertility with a prevalence of 6%-10%, primarily affecting testicular and epididymal function and ultimately compromising sperm quality. However, most infertile patients with genital infection/inflammation are asymptomatic and easily overlooked. Traditional indicators, including white blood cells, elastase, and other components in semen, can reflect inflammation of the genital tract, but there is still a lack of a uniform standard method of detection. Therefore, it is necessary to explore reliable markers in semen that reflect the inflammatory status of the genital tract. Using the experimental autoimmune orchitis (EAO) model to simulate noninfectious chronic orchitis, we successfully collected ejaculated seminal fluid from EAO rats using optimized electrical stimulation devices. Proteomic analysis was performed using isobaric tags for relative and absolute quantification (iTRAQ). Compared to the control group, 55 upregulated and 105 downregulated proteins were identified in seminal plasma samples from the EAO group. In a preliminary screening, the inflammation-related protein S100A8/A9 was upregulated. We further verified that S100A8/A9 was increased in seminal plasma and highly expressed in testicular macrophages of the EAO model. In patients with oligoasthenospermia and genital tract infections, we also found that S100A8/A9 levels were remarkably increased in seminal plasma and testicular macrophages. S100A8/A9 in semen may be a potential biomarker for chronic genital inflammation. Our study provides a new potential biomarker for early diagnosis and further understanding of male infertility caused by genital inflammation.

Comparison of outcomes in three surgical techniques for proximal hypospadias: staged transverse preputial island flap urethroplasty versus single-stage repairs.

To evaluate and compare the outcomes and complications of three different surgical techniques for treating primary proximal hypospadias with ventral curvature (VC) ≥30°, we retrospectively reviewed the medical records of patients who underwent primary repair of proximal hypospadias with VC ≥30° after degloving at Beijing Children's Hospital Affiliated to Capital Medical University (Beijing, China) from January 2019 to January 2021. A total of 152 patients were divided into three groups: transverse preputial island flap (TPIF) combined with Duplay, modified Koyanagi, and staged TPIF, which were performed on 55, 16, and 81 patients, respectively. A total of 39 (25.7%) patients had complications. Complications rates were similar for the TPIF combined with the Duplay group (40.0%) and modified Koyanagi group (50.0%) but lower for the staged TPIF group (11.1%; P < 0.01). The incidence of urethrocutaneous fistulas was significantly higher in TPIF combined with Duplay group (21.8%) compared to staged TPIF group (4.9%; P = 0.01). In univariate analysis, the length of the urethral defect was the single factor that could predict complications; the cutoff was 4.55 cm. More patients in the long urethral defect group than in the short one had complications (34.1% vs 15.7%, P = 0.01). These results indicate that staged TPIF produced a better outcome, whereas more patients in the TPIF combined with Duplay group presented with two or more complications.

Microbiology and immune mechanisms associated with male infertility.

Up to 50% of infertility is caused by the male side. Varicocele, orchitis, prostatitis, oligospermia, asthenospermia, and azoospermia are common causes of impaired male reproductive function and male infertility. In recent years, more and more studies have shown that microorganisms play an increasingly important role in the occurrence of these diseases. This review will discuss the microbiological changes associated with male infertility from the perspective of etiology, and how microorganisms affect the normal function of the male reproductive system through immune mechanisms. Linking male infertility with microbiome and immunomics can help us recognize the immune response under different disease states, providing more targeted immune target therapy for these diseases, and even the possibility of combined immunotherapy and microbial therapy for male infertility.

The value of lipid metabolites 9,10-DOA and 11,12-EET in prenatal diagnosis of fetal heart defects.

AIMS: To explore the maternal metabolic changes of fetal congenital heart disease (FCHD), and screen metabolic markers to establish a practical diagnostic model. METHODS: Maternal peripheral serum from 17 FCHD and 63 non-FCHD pregnant were analyzed by Ultra High-performance Liquid Chromatography-Mass/Mass (UPLC-MS/MS). RESULTS: In the FCHD and the non-FCHD, 132 metabolites were identified, including 35 differential metabolites enriched in the purine, caffeine, primary bile acid, and arachidonic acid metabolism pathway. Finally, the screened (+/-)9,10-dihydroxy-12Z-octadecenoic acid (AUC = 0.888) and 11,12-epoxy-(5Z,8Z,11Z)-icosatrienoic acid (AUC = 0.995) were incorporated into the logistic regression model. The AUC value of the two-metabolite model was 1.0, superior to proline (AUC = 0.867), uric acid (AUC = 0.789), glutamine (AUC = 0.705), and taurine (AUC = 0.923) previously reported. The clinical decision curve analysis (DCA) showed the highest clinical net benefit of the model, and internal validation by bootstrap shows the robustness of the model (Brier Score = 0.005). CONCLUSION: For the prenatal diagnosis of CHD, our findings are of great clinical significance. As an additional screening procedure, the identification model might be used to detect.

Dose-response mapping of MEHP exposure with metabolic changes of trophoblast cell and determination of sensitive markers.

Mono(2-ethylhexyl) phthalate (MEHP) is a metabolite of DEHP which is one of phthalic acid esters (PAEs) widely used in daily necessities. Moreover, MEHP has been proven to have stronger biological toxicity comparing to DEHP. In particular, several recent population-based studies have reported that intrauterine exposure to MEHP results in adverse pregnancy outcomes. To explore the mechanisms and metabolic biomarkers of MEHP exposure, we examined the metabolic status of HTR-8/Svneo cell lines exposed to different doses of MEHP (0, 1.25, 5.0, 20 µM). Global and dose-response metabolomics tools were used to identify metabolic perturbations and sensitive markers associated with MEHP. Only 22 metabolic features (accounted for <1 %) were significantly changed when exposed to 1.25 µM. However, when the exposure dose was increased to 5 or 20 µM, the number of significantly changed metabolic features exceeded 300 (approximately 10 %). In particular, amino acid metabolism, pyrimidine metabolism and glutathione metabolism were widely affected according to the enrich analysis of those significant altered metabolites, which has and have previously been reported to be closely related to fetal development. Moreover, 5'-UMP and N-acetylputrescine with the lowest effective concentrations (EC-10 = 0.1 µM and EC+10 = 0.11 µM, respectively) were identified as sensitive endogenous biomarkers of MEHP exposure.

Effectiveness of penile ventral curvature correction and the trend of hypospadias repair: a prospective study of the national center in China.

BACKGROUND: Hypospadias repair is a complex surgical procedure that involves correcting penile ventral curvature (VC) and performing urethroplasty. This study aims to evaluate the effectiveness of different strategies for VC correction and analyse the trends in hypospadias repair at a national centre in China. METHODS: Prospective data collection was conducted from 2019 to 2020 for patients undergoing hypospadias repair. The effectiveness of VC correction was assessed based on the degree of VC change with different strategies. Furthermore, the choice of surgical techniques for different types of hypospadias repair was analysed. RESULTS: A total of 434 patients were included, with a median preoperative VC degree of 50° (35°, 70°). All patients achieved a straight penis postoperatively, with 15.2% undergoing degloving, 28.6% undergoing degloving and dorsal plication (DP), 13.1% undergoing degloving and urethral plate transection (UPT), and 43.1% undergoing degloving, UPT and DP. Degloving alone was effective in correcting VC in 57.6% of patients with VC less than 30°. In our analysis, DP after UPT resulted in a higher degree of correction (25°) compared with DP after degloving alone (20°) (p<0.001). The study identified the current trends in hypospadias repair, with tubularised incised plate urethroplasty (TIP) being the most common technique used in distal hypospadias repair (70.6% of patients) and transverse preputial island flap urethroplasty (TPIFU) being preferred for proximal hypospadias repair (63.0%). CONCLUSIONS: Degloving alone is effective for correcting VC less than 30°. The majority of patients in our centre underwent UPT, and DP after UPT yielded better results compared with DP after degloving alone. Distal hypospadias repair commonly used TIP, while TPIFU was favoured for proximal hypospadias repair. TRIAL REGISTRATION NUMBER: ChiCTR1900023055.

Testicular exosomes disturb the immunosuppressive phenotype of testicular macrophages mediated by miR-155-5p in uropathogenic Escherichia coli-induced orchitis.

Male reproductive infections are known to shape the immunological homeostasis of the testes, leading to male infertility. However, the specific pathogenesis of these changes remains poorly understood. Exosomes released in the inflammatory microenvironment are important in communication between the local microenvironment and recipient cells. Here, we aim to identify the immunomodulatory properties of inflammatory testes-derived exosomes (IT-exos) and explore their underlying mechanisms in orchitis. IT-exos were isolated using a uropathogenic Escherichia coli (UPEC)-induced orchitis model and confirmed that IT-exos promoted proinflammatory M1 activation with increasing expression of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) in vitro. We further used small RNA sequencing to identify the differential miRNA profiles in exosomes and primary testicular macrophages (TMs) from normal and UPEC-infected testes, respectively, and identified that miR-155-5p was highly enriched in IT-exos and TMs from inflammatory testes. Further study of bone marrow derived macrophages (BMDMs) transfected with miR-155-5p mimic showed that macrophages polarized to proinflammatory phenotype. In addition, the mice that were administrated IT-exos showed remarkable activation of TM1-like macrophages; however, IT-exos with silencing miR-155-5p showed a decrease in proinflammatory responses. Overall, we demonstrate that miR-155-5p delivered by IT-exos plays an important role in the activation of TM1 in UPEC-induced orchitis. Our study provides a new perspective on the immunological mechanisms underlying inflammation-related male infertility.