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Aquaculture makes great contribution to global food production. The aquaculture capture scale of China was far ahead of other countries in the world. Despite the potential role of dissolved organic matter (DOM) to affect fish growth and ecological cycle, the characterization of DOM in aquaculture industry was poorly understood. In this study, fluorescence excitation-emission matrix (EEM) spectroscopy and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) were conducted to decipher the optical and molecular signatures of DOM in freshwater aquaculture ponds in Eastern China. The EEM dataset was decomposed by parallel factor analysis (PARAFAC). Three main components including humic/fulvic acid-like (C1 and C3), tryptophan-like (C2) and tyrosine-like substances (C3) were obtained. FT-ICR-MS identified DOM composition at molecular level. In terms of formula classes, the dominant CHO species were followed by CHON and CHOS groups. According to compound classification criteria, the key components of lignins, tannins, proteins and lipids illustrated the primary source from terrestrial sediment, feeding doses and stocked creatures, implying the great influence by the land-based aquaculture ponds. Typical spectral indexes such as humification index (HIX), biological index (BIX) and fluorescence index (FI) consistently reflected the lower humification degree of DOM and greater contribution from protein-like sources. Furthermore, to utilize readily available spectral indexes to predict the time-consuming molecular properties, redundancy analysis and the pairwise correlation analysis was carried out to prove that two spectral indexes (E2:E3 and BIX) were negatively associated with four molecular formula derived parameters (O/Cwa, AImodwa, DBEwa and NOSCwa). The findings expanded our understanding of aquaculture DOM evolved in environmental chemistry.

The purpose of this study was to use chemical similarity evaluations, transcriptional profiling, in vitro toxicokinetic data, and physiologically based pharmacokinetic (PBPK) models to support read-across for a series of branched carboxylic acids using valproic acid (VPA), a known developmental toxicant, as a comparator. The chemicals included 2-propylpentanoic acid (VPA), 2-ethylbutanoic acid, 2-ethylhexanoic acid (EHA), 2-methylnonanoic acid, 2-hexyldecanoic acid, 2-propylnonanoic acid (PNA), dipentyl acetic acid or 2-pentylheptanoic acid, octanoic acid (a straight chain alkyl acid), and 2-ethylhexanol. Transcriptomics was evaluated in 4 cell types (A549, HepG2, MCF7, and iCell cardiomyocytes) 6 h after exposure to 3 concentrations of the compounds, using the L1000 platform. The transcriptional profiling data indicate that 2- or 3-carbon alkyl substituents at the alpha position of the carboxylic acid (EHA and PNA) elicit a transcriptional profile similar to the one elicited by VPA. The transcriptional profile is different for the other chemicals tested, which provides support for limiting read-across from VPA to much shorter and longer acids. Molecular docking models for histone deacetylases, the putative target of VPA, provide a possible mechanistic explanation for the activity cliff elucidated by transcriptomics. In vitro toxicokinetic data were utilized in a PBPK model to estimate internal dosimetry. The PBPK modeling data show that as the branched chain increases, predicted plasma Cmax decreases. This work demonstrates how transcriptomics and other mode of action-based methods can improve read-across.

The toxic effect of di(2-ethylhexyl) phthalate (DEHP) on prepubertal testes was examined in this study. We treated 3-week-old male mice with 4.8 mg/kg/day (milligram/kilogram/day) (no observed adverse effect level), 30 mg/kg/day (high exposure dose relative to humans), 100 mg/kg/day (level causing a reproductive system disorder), and 500 mg/kg/day (dose causing a multigenerational reproductive system disorder) of DEHP via gavage. Obvious abnormalities in the testicular organ coefficient, spermatogenic epithelium, and testosterone levels occurred in the 500 mg/kg DEHP group. Ribonucleic acid sequencing (RNA-seq) showed that differentially expressed genes (DEGs) in each group could enrich reproduction and reproductive process terms according to the gene ontology (GO) results, and coenrichment of metabolism pathway was observed by the Reactome pathway analysis. Through the analysis of common genes in the metabolism pathway, we discovered that DEHP exposure at 4.8 to 500 mg/kg or 100 mg/kg caused the same damages to the prepubertal testis. In general, we identified two key transcriptional biomarkers (fatty acid binding protein 3 (Fabp3) and carboxylesterase (Ces) 1d), which provided new insight into the gene regulatory mechanism associated with DEHP exposure and will contribute to the prediction and diagnosis of prepuberty testis injury caused by DEHP.

Phthalates are ubiquitous in the environment and they can penetrate the human body via multiple routes. However, the impact of phthalates on human male reproductive disorders remains unclear.A critical review of published studies was conducted to clarify the association of phthalates and male reproductive disorders and to highlight future research needs. PubMed, Cochrane Library, and Web of Science Database were systematically searched for relevant articles written in English, independent of region and time period. If more than one paper overlapped in study design or participants included, the most recent manuscript was included in our review. Due to limited homogeneous statistical data, observed trends were summarized to draw approximate conclusions.Nineteen manuscripts were included in our final analysis. Exposure to di-(2-ethylhexyl) phthalate (DEHP), di-n-butyl phthalate (DBP), diethyl phthalate (DEP), and/or benzyl butyl phthalate (BBP) is associated with a shorter anogenital distance (AGD). Meanwhile, exposure to DEHP and/or di-isodecyl phthalate (DIDP) is associated with higher risks for cryptorchidism and hypospadias.Generic exposure to phthalates has an adverse effect on human reproductive development, especially exposure to DEHP, DBP, DEP, BBP, and DIDP. A critical time for exposure sensitivity is during early pregnancy. Due to the lack of significant statistical power in this study, the conclusions drawn should be cautiously interpreted and they remain to be validated. Thus, additional well-designed studies, as well as propaganda and education regarding phthalate exposure and safer substitutes for these compounds, are greatly needed.

This paper describes a rapid method to simultaneously determine acetochlor, fluorochloridone and pendimethalin present in a herbicide emulsifiable concentrate (EC) formulation using gas chromatography–mass spectrometry (GC–MS). Selected ion monitoring mode was performed to increase the sensitivity, with dibutyl phthalate as an internal standard. The method was validated with respect to linearity, accuracy, precision, and stability. Chromatographic separation was carried out on a TG-5 MS column (30 m × 0.25 mm × 0.25 μm) with helium as the carrier gas at a flow rate of 1.0 mL/min. Calibration curves were linear over 2.0–20.0 μg/mL for each analyte, and the limit of quantification was below 20 ng/mL. Good performance in terms of recovery ranging from 94.5% to 102.5% at 3 concentration levels proved excellent accuracy. The intra- and inter-day relative standard deviations for 6 replicate measurements were always less than 5%. The developed method is simple and efficient for the routine determination of the ternary mixtures in a compound herbicide EC formulation product.

To assess the accuracy of contralateral testis hypertrophy for predicting the fate of nonpalpable testis in Chinese boys at different ages.The data of patients who presented with unilateral impalpable testis and who underwent laparoscopy at the Children's Hospital of Chongqing Medical University between January 1, 2000 and January 1, 2018 were reviewed. The boys were divided into four groups: age-matched volunteers with no testicular abnormalities represented the control group (group I), boys with palpable undescended testis (group II), boys with nonpalpable testis (NPT)/viable testis (VT) (group III), and boys with NPT/non-viable testis (NVT) group (group IV). Scrotal testes were prospectively measured by ultrasonography for volume and size, and diagnostic laparoscopy was performed to determine the state of the cryptorchid testis.The mean contralateral testicular volume and length in the boys with an absent testis was 0.78mL and 17mm compared with 0.67mL and 15mm in the boys with a testis present and 0.63mL and 15mm in the controls, respectively (P0.05). The predictive accuracy, sensitivity, and specificity for an absent testis were 64.9%, 75%, and 49%, respectively, for volume and 64.2%, 56.3%, and 76.4%, respectively for length at the optimal cutoff value of 0.65mL volume and 16.55mm length. Contralateral testis volume was the most accurate in predicting monorchism in 0-2-year-olds (sensitivity: 75%, specificity: 70%, accuracy: 73.1%) and the contralateral testicular length was most accurate for 4-6-years-old (sensitivity: 68.6%; specificity: 77.8%; accuracy: 72.2%). We also included 29 patients with bilateral undescended testis (UDT) and with unilateral nonpalpable. Cutoff values for testicular volume and length were 0.6mL (sensitivity: 81.8%, specificity: 88.9%, accuracy: 86.2%) and 13.5mm (sensitivity: 63.6%, specificity: 77.8%, accuracy: 77.8%).The present results exclusively obtained from laparoscopic exploration suggest that a testis volume of0.65mL or a testis length of16.55mm could predict monarchism with an accuracy of about 65%. In younger patients aged 0-2 years and 4-6 years, the overall predictive accuracy increases to about 73% but laparoscopic exploration is still required.

To systematically evaluate the efficacy, safety, and treatment-related outcomes between percutaneous radiofrequency ablation (PtRFA) and partial hepatectomy (PH) for small primary liver cancer meeting the Milan criteria.A systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. A priori protocol was registered in the PROSPERO database, and a literature search of all relevant studies published on PubMed, Cochrane library, Web of Science database, and Science Direct until July 2019 was performed. Only randomized controlled trials published in English were eligible for inclusion.Of the 385 identified articles, only five randomized controlled trials involving 761 adult patients with small liver cancer were included in the final analysis. The 1-year, 2-year, 3-year, 4-year, 5-year overall survival and disease-free survival between PtRFA and PH did not reach significant difference (P-value0.05). The long-term recurrence rate was higher and the recurrence-free survival was lower in patients treated with PtRFA compared with those treated with PH (P-value0.05), but short-term (1-year) comparisons did not reach statistical significance. With regard to treatment-related complications, serious adverse event risks, analgesics needs, hospital stay and costs, PtRFA had significant superiority compared with PH.The overall treatment effects of PtRFA are comparable to PH for small liver cancer. Though patients with PtRFA have a higher long-term recurrence rate, these patients share less complications, few serious adverse event risks, less analgesics needs, shorter hospital stay, and lower costs. PtRFA may be recommended as the preferred treatment of solitary liver tumors3cm in diameter.

Di-(2-ethylhexyl) phthalate (DEHP) is a common plasticizer, which is known to be an environmental endocrine-disrupting chemical that can jeopardize the male reproductive system. Prepuberal exposure to DEHP leads to steroidogenesis disorders. However, the specific mechanism remains ambiguous. Therefore, Sprague Dawley (SD) rats underwent prepuberal DEHP exposure at a dose of 500 mg/kg per day through gavage. Additionally, the resulting testicular injury was evaluated to confirm the disturbed steroidogenesis. Changes in testicular histology, significant reduction of serum testosterone (P < 0.01) and luteinizing hormone (P < 0.001), and significantly decreased expressions of steroidogenic acute regulatory protein (P < 0.01) and 3-beta-hydroxysteroid dehydrogenase (P < 0.05) were found in DEHP-treated rats. DEHP exposure resulted in obvious intestinal damage and oxidative stress imbalance, primarily in the jejunum. Both the activation of the nuclear factor-E2-related factor 2 (Nrf2) signaling pathway and alterations of microbiota profiles were observed in all three gut specimens, but were most notable in the jejunum. We hypothesize that the gut-microbiota-testis axis, which is mediated by the activation of the Nrf2 antioxidant pathway, could be involved in the dysfunction of prepuberal steroidogenesis induced by DEHP.

Chemical leukoderma is an acquired depigmentation of the skin caused by repeated exposure to specific agents damaging to epidermal melanocytes. Case reports of chemical leukoderma have been associated with some consumer products. To date, there are no well-accepted approaches for evaluating and minimizing this risk. To this end, a framework is presented that evaluates the physical and chemical characteristics of compounds associated with chemical leukoderma and employs structure-activity relationship (SAR) read-across and predictive metabolism tools to determine whether a compound is at increased risk of evoking chemical leukoderma. In addition to in silico approaches, the testing strategy includes in chemico quinone formation and in vitro melanocyte cytotoxicity assays to dimension the risk as part of an overall weight of evidence approach to risk assessment. Cosmetic ingredients raspberry ketone, undecylenoyl phenylalanine, tocopheryl succinate, p-coumaric acid, resveratrol, resveratrol dimethyl ether, sucrose dilaurate, tranexamic acid, niacinamide and caffeic acid are evaluated in this framework and compared to positive controls rhododendrol and hydroquinone. Overall, this framework is considered an important step toward mitigating the risk of chemical leukoderma for compounds used in consumer products.

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.

Objective To report a rare case of a kidney lesion, finally diagnosed as inflammatory pseudotumor, underwent partial nephrectomy and saved the kidney. Methods Case report and experience sharing. Results A 4-year-old boy expressed merely occasionally abdominal pain with space-occupying lesion of the right kidney that was indicative of renal malignant carcinoma. The boy underwent partial nephrectomy and perinephric lymph node dissection, and the mass was histopathologically diagnosed as IPT of renal parenchyma, accompanied with lymph nodes reactive hyperplasia. During the subsequent 20 months' follow-up, the child was all clinically very well, the residual right kidney regrew approximately to the same size as the left one by catch-up growth, remained normal glomerular filtration rate, and did not require additional therapy. Conclusion Among the affected organs of IPT, kidney is indeed of rare involvement, especially in children. Children has immeasurable potentiality for restoration and regeneration, IPT of the kidney should be given sufficient attention when confronted patients with renal mass lesion in the differential diagnosis, to avoid unnecessary surgical intervention.

The blood–testis barrier (BTB) and apical ectoplasmic specialization (ES), which are synchronized through the crosstalk of Sertoli cells and Sertoli germ cells, are required for spermatogenesis and sperm release. Here, we show that Wnt5a, a noncanonical Wnt signaling pathway ligand, is predominately expressed in both the BTB and apical ES and has a specific expression pattern during the seminiferous epithelium cycle. We employed siRNA to knockdown Wnt5a expression in testis and Sertoli cells, and then identified elongated spermatids that lost their polarity and were embedded in the seminiferous epithelium. Moreover, phagosomes were found near the tubule lumen. These defects were due to BTB and apical ES disruption. We also verified that the expression level and/or location of BTB-associated proteins, actin binding proteins (ABPs), and F-actin was changed after Wnt5a knockdown in vivo and in vitro. Additionally, we demonstrated that Wnt5a regulated actin dynamics through Ror2-mediated mTORC1 and mTORC2. This study clarified the molecular mechanism of Wnt5a in Sertoli cell junctions through the planar cell polarity (PCP) signaling pathway. Our findings could provide an experimental basis for the clinical diagnosis and treatment of male infertility caused by Sertoli cell junction impairment.

To systematically evaluate the incidence characteristics of testicular microlithiasis (TM) in children and its association with primary testicular tumors (PTT). A systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. A priori protocol was registered in the PROSPERO database (CRD42018111119), and a literature search of all relevant studies published until February 2019 was performed. Prospective, retrospective cohort, or cross-sectional studies containing ultrasonography (US) data on the incidence of TM or the association between TM and PTT were eligible for inclusion. Of the 102 identified articles, 18 studies involving 58,195 children were included in the final analysis. The overall incidence of TM in children with additional risk factors for PTT was 2.7%. In children, the proportion of left TM in unilateral cases was 55.7%, the frequency of bilateral TM was 69.0%, and proportion of classic TM was 71.8% [95% confidence interval (CI) 62.4–81.1%, P = 0.0, I2 = 0.0%]. About 93.5% of TM remained unchanged, and newly detected PTT rate was very low (4/296) during follow-up. The overall risk ratio of TM in children with a concurrent diagnosis of PTT was 15.46 (95% CI 6.93–34.47, P

Mitochondrial DNA (mtDNA) is an attractive cellular target for anticancer agents in addition to nuclear DNA (nDNA). The cationic platinum(II) complex cis-[Pt(NP)(NH3)2Cl]NO3 (PtNP, NP = N-(2-ethylpyridine)-1,8-naphthalimide) bearing the DNA-intercalating moiety NP was designed. The structure of PtNP was fully characterized by single-crystal X-ray crystallography, NMR, and HRMS. PtNP is superior to cisplatin in both in vitro and in vivo anticancer activities with low systemic toxicity. The interaction of PtNP with CT-DNA demonstrated that PtNP could effectively bind to DNA through both covalent and noncovalent double binding modes. In addition to causing significant damage to nDNA and remarkable inhibition to DNA damage repair, PtNP also distributed in mitochondria, inducing mtDNA damage and affecting the downstream transcriptional level of mitochondrion-encoded genes. In addition, PtNP disturbed the physiological processes of mitochondria by reducing the mitochondrial membrane potential and promoting the generation of reactive oxygen species. Mechanistic studies demonstrate that PtNP induced apoptosis via mitochondrial pathways by upregulating Bax and Puma and downregulating Bcl-2 proteins, leading to the release of cytochrome c and activation of caspase-3 and caspase-9. As a dual-DNA-damage agent, PtNP is able to improve the anticancer activity by damaging both nuclear and mitochondrial DNA, thus providing a new anticancer mechanism of action for the naphthalimide monofunctional platinum(II) complexes.

In the context of REACH and the EU ban on animal testing of cosmetic ingredients, development, adoption and acceptance of non-animal methods is urgent. Read-across is the predominate non-animal method being used for higher tier endpoints (repeat dose and developmental and reproductive toxicity). The limitations of read-across include the lack of suitable analogs and analog data for all chemicals of interest, as well as concerns with missing a potential adverse response that results from small differences in chemical structure. In this manuscript we explore two possible enhancements to read-across approaches in the context of a single case study: read-across assessments based on metabolite data and incorporation of in vitro data to support the read-across hypothesis. We use this case study to explore possible paths forward in implementing these enhancements, but more importantly to raise issues that need to be resolved prior to extensive use and hopefully acceptance of these expanded approaches. For the case of read-across based on metabolites, we explore the potential application of an internal dose TTC (iTTC) approach to address uncertainty associated with potential toxicity from exposure to residual parent chemical. This is a relevant scenario for the many cosmetic ingredients containing ester structures. For the use of in vitro data we explore considerations that must be taken before the application of ToxCast™ data to the read-across to ensure positive responses are reliable and relevant. As more cosmetic ingredients are tested in in vitro systems, guidance on the appropriate interpretation of these data will be essential. The concept of dosimetry is a unifying need that must be addressed in both these approaches. In the present paper, we explore how to use and apply internal dose metrics to address some issues associated with expanded approaches in read-across.

Long-term exposure to particulate matter 2.5 (PM2.5) from automobile exhaust impairs spermatogenesis through oxidative stress injury, but the underlying mechanism is unknown. To investigate the toxic mechanism of PM2.5-induced spermatogenesis impairment, we focused on the MAPK signaling pathway. We also examined the effects of treatment with vitamins C and E on spermatogenic function. Male SD rats were divided randomly into three groups: control (0.9% sterilized saline), PM2.5 exposure (20 mg/kg.b.w.), and PM2.5 exposure (20 mg/kg.b.w.) with vitamin intervention (vitamin C, 100 mg/kg.b.w.; vitamin E, 50 mg/kg.b.w.). Male rats showed a marked decline in fertility and decreased sperm quality after PM2.5 exposure. The expression of SOD and Nrf2 was significantly decreased, and that of MDA was increased markedly. The expression of blood–testis barrier–associated proteins, such as ZO-1, occludin, connexin 43, and β-catenin, was significantly decreased, the Bcl-2/Bax ratio was downregulated, and the cleaved caspase-3 level was increased. Phosphorylation of MAPKs, including ERKs, JNKs, and p38, was upregulated. Treatment with vitamins C and E reversed the damage induced by PM2.5 exposure. These results suggest that PM2.5 from automobile exhaust disrupted spermatogenesis via ROS-mediated MAPK pathways, and that a combined vitamin C and E intervention effectively mitigated toxicity in the male reproductive system.

Di-(2-ethylhexyl) phthalate (DEHP) is an environmental endocrine disruptor that accumulates in organisms in various ways and induces male reproductive system disorders. In this study, we established a testicular injury model by gavage with different concentrations of DEHP. The testes were then collected for RNA sequencing (RNA-seq), and the results were analyzed by bioinformatics and verified by experiments. Our research results show that different concentrations of DEHP interfere with testicular development differently. Weighted gene coexpression network analysis (WGCNA) generated sixteen modules and identified the turquoise module as key. Then, estrogen receptor 1 (ESR1), filamin A (Flna) and Furin were identified as hub genes. qPCR and immunohistochemistry results revealed that all three hub genes were upregulated. We detected the locations of these genes by immunohistochemistry. ESR1 was mainly located in Leydig cells; Flna immunostaining is observed in the Leydig and some germ cells and Furin staining was seen in almost all types of testicular cells. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed enrichment mainly in MAPK signaling pathways, p53 signaling pathways, HIF-1 signaling pathways, protein processing in the endoplasmic reticulum, apoptosis, the cell cycle, RNA degradation, etc. This is the first study using WGCNA to investigate the mechanism of DEHP-induced injury in the prepubertal testis, providing new research angles to further understand the mechanism of DEHP-induced injury in the prepubertal testis.

The etiology of hypospadias and cryptorchidism, which are the two most common genital anomalies in males, has not been elucidated. Although prenatal exposure to endocrine-disrupting chemicals (EDCs) may increase the risks of hypospadias and cryptorchidism, the associations have not been confirmed. Therefore, we performed a meta-analysis to establish the relationships between prenatal exposure to EDCs and male genital anomalies. A systematic search of PubMed, EMbase, and Cochrane Library CENTRAL for relevant published studies providing quantitative data on the associations between prenatal EDCs exposure and hypospadias/cryptorchidism in humans was conducted. In total, sixteen case-controlled studies were included. Prenatal exposure to overall EDCs was associated with an increased risk of hypospadias in males (OR, 1.34, 95 % CI 1.12 to 1.60). Although there was no statistically significant association between overall EDCs exposure and cryptorchidism (OR, 1.11, 95 % CI 0.99 to 1.24), exposure to phenol substances was associated with an increased risk of cryptorchidism (OR, 1.81, 95 % CI, 1.12 to 2.93). Using the GRADE tool, we found the overall evidence to be of moderate certainty. In conclusion, the current evidence suggests prenatal EDCs exposure may increase the risk of hypospadias in males.

Preterm birth is the second most common cause of death in children under 5 years of age. The etiology of preterm birth has not yet been elucidated. Although maternal exposure to endocrine disrupting chemicals (EDCs) may increase the risk for preterm birth, associations have not been confirmed. We performed a meta-analysis to elucidate the relationships between maternal exposure to EDCs and preterm birth. A systematic search of PubMed, Ovid-EMBASE, and the Cochrane Library (CENTRAL) for relevant published studies providing quantitative data on the association between maternal EDC exposure and preterm birth in humans was conducted in July 2021. To calculate the overall estimates, we pooled the adjusted regression coefficients with 95% confidence intervals (CIs) from each study by the inverse variance method. A total of 59 studies were included. The pooled results indicated that maternal exposure to metals (OR, 1.23; 95% CI, 1.17 to 1.29) and phthalates (OR, 1.31; 95% CI, 1.21 to 1.42) was related to an increased risk for preterm birth. Specifically, maternal exposure to lead, cadmium, chromium, copper and manganese appeared to be correlated with an elevated risk for preterm birth. Additionally, maternal exposure to monoethyl phthalate (MEP), mono-2-ethyl-5-carboxypentyl phthalate (MECPP), monobenzyl phthalate (MBzP), and di (2-ethylhexyl) phthalate (DEHP) was also associated with preterm birth. In conclusion, maternal exposure to metals and phthalates may increase the risk for preterm birth based on current evidence.

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.

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.

Background The aim of this study was to quantify the impact of coronavirus disease 2019 (COVID-19) on pediatric operations, and establish preoperative, intraoperative, and postoperative protocols to improve the pediatric operations. Methods We here compare the number of patients who underwent surgery in Chongqing Medical University Affiliated Children’s Hospital during the pandemic (January 23–March 11), after the pandemic (March 12–April 30), after our measures were put in place (May 1–May 21), and the equivalent period in 2019. Result During the COVID-19 pandemic, 62.68% fewer patients underwent surgery than during the homologous period of time 1 year earlier (P P Conclusion This outbreak of COVID-19 has affected not only individuals with COVID-19 but also patients seeking surgical operations. Understanding the present situation helps clinicians provide a high level of treatment to all children.

Objective To describe and summarize the early diagnosis, treatment and outcomes of obstructed hemivagina and ipsilateral renal anomaly (OHVIRA). Methods Data from patients with OHVIRA treated at the study centre over the last decade were analysed retrospectively, including demographic characteristics, symptoms, diagnosis, treatment and outcomes. Relevant published literature was also reviewed in this study. Results In total, 11 cases were diagnosed with OHVIRA over the study period, ranging in age from 3 to 14 years (median 11 years). Four cases were asymptomatic, four had abdominal pain and three had urinary symptoms. All 11 cases underwent vaginoplasty. Ureteral bladder re-implantation (n = 1), dysplastic nephrectomy (n = 1), separation of labia minora adhesions (n = 1), perineoplasty (n = 1) and urethroplasty (n = 1) were performed. Cases were followed up for 2 months to 8 years (median 5 years) with good follow-up outcomes. Conclusions Based on the cases in this study and the relevant literature, ultrasound appears to be an effective method for the diagnosis of OHVIRA. Experienced ultrasonographers are able to achieve a high corrected diagnosis rate. The differential diagnosis of OHVIRA should be considered by paediatric surgeons, urologists, emergency physicians and gynaecologists when they identify patients with didelphys uterus or renal agenesis. Early surgery can reduce the risk of potential genital tract infection and gynaecological complications.

Postnatal surge of gonadotrophins, Luteinizing hormone (LH) and Follicle-Stimulating hormone (FSH) known as minipuberty, is critical for gonocyte maturation into spermatogonial stem cells (SSC) in the testis. Gonadotrophins are essential for optimum fertility in men, but very little is known how they regulate germ cells during minipuberty. This study examined whether gonadotrophins play a role on gonocyte transformation in vivo. Testes from hypogonadal (hpg) mice and their wild type (WT) littermates (n = 6/group) were weighed, and processed in paraffin at postnatal days (D) 0, 3, 6 and 9. Mouse VASA homologue (germ cell marker), anti-Mullerian hormone (Sertoli cell marker) antibodies and DAPI (nuclei marker) were used for immunofluorescence followed by confocal imaging. Germ cells on or off basement membrane (BM) and Sertoli cells/tubule were counted using Image J and analyzed with GraphPad. Comparing to WT littermates, there were significantly fewer germ cells on BM/tubule (p

N6-methyladenosine (m6A) modification, the most prevalent form of RNA methylation, modulates gene expression post-transcriptionally. Di-(2-ethylhexyl) phthalate (DEHP) is a common environmental endocrine disrupting chemical that induces testicular injury due to the inhibition of the demethylase fat mass and obesity-associated protein (FTO) and increases the m6A modification. How FTO-mediated m6A modification in testicular Leydig cell injury induced by DEHP remains unclear. Here, the TM3 Leydig cell line was treated with mono-(2-ethylhexyl) phthalate (MEHP), the main metabolite of DEHP in the body, as well as FB23-2, an inhibitor of FTO. Decreased levels of testosterone in the culture supernatant, significantly increased apoptosis, and a remarkable upregulation of global m6A modification were found in both TM3 cells treated with MEHP and FB23-2. Transcriptome sequencing showed that both treatments significantly induced apoptosis-associated gene expression. Methylated RNA immunoprecipitation sequencing showed that the Leydig cell injury induced by upregulated m6A modification could be associated with multiple physiological disorders, including histone acetylation, reactive oxygen species biosynthesis, MAPK signaling pathway, hormone secretion regulation, autophagy regulation, and male gonadal development. Overall, the inhibition of FTO-mediated up-regulation of m6A could be involved in MEHP-induced Leydig cell apoptosis.