Search

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.

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.

The liver is the most common target organ in toxicology studies. The development of chemical structural alerts for identifying hepatotoxicity will play an important role in in silico model prediction and help strengthen the identification of analogs used in structure activity relationship (SAR)- based read-across. The aim of the current study is development of an SAR-based expert-system decision tree for screening of hepatotoxicants across a wide range of chemistry space and proposed modes of action for clustering of chemicals using defined core chemical categories based on receptor-binding or bioactivation. The decision tree is based on ∼ 1180 different chemicals that were reviewed for hepatotoxicity information. Knowledge of chemical receptor binding, metabolism and mechanistic information were used to group these chemicals into 16 different categories and 102 subcategories: four categories describe binders to 9 different receptors, 11 categories are associated with possible reactive metabolites (RMs) and there is one miscellaneous category. Each chemical subcategory has been associated with possible modes of action (MOAs) or similar key structural features. This decision tree can help to screen potential liver toxicants associated with core structural alerts of receptor binding and/or RMs and be used as a component of weight of evidence decisions based on SAR read-across, and to fill data gaps.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

Discussion on the role of DEHP in the critical period of gonadal development in pregnant rats (F0), studied the evolution of F1-F4 generation of inter-generational inheritance of cryptorchidism and the alteration of DNA methylation levels in testis. Pregnant SD rats were randomly divided into two groups: normal control group and DEHP experimental group. From pregnancy 7 d to 19 d, experimental group was sustained to gavage DEHP 750 mg/kg bw/day, observed the incidence of cryptorchidism in offspring and examined the pregnancy rate of female rats through mating experiments. Continuous recording the rat's weight and AGD value, after maturation (PND80) recording testis and epididymis' size and weight, detected the sperm number and quality. Subsequently, we examined the evolution morphological changes of testicular tissue for 4 generation rats by HE staining and Western Blot. Completed the MeDIP-sequencing analysis of 6 samples (F1 generation, F4 generation and Control). DEHP successfully induced cryptorchidism occurrence in offspring during pregnancy. The incidence of cryptorchidism in F1 was 30%, in F2 was 12.5%, and there was no cryptorchidism coming up in F3 and F4. Mating experiment shows conception rate 50% in F1, F2 generation was 75%, the F3 and F4 generation were 100%. HE staining showed that the seminiferous epithelium of F1 generation was atrophy and with a few spermatogenic cell, F2 generation had improved, F3 and F4 generation were tend to be normal. The DNA methyltransferase expression was up-regulated with the increase of generations by Real Time-PCR, immunohistochemistry and Western Blot. MeDIP-seq Data Analysis Results show many differentially methylated DNA sequences between F1 and F4. DEHP damage male reproductive function in rats, affect expression of DNA methyltransferase enzyme, which in turn leads to genomic imprinting methylation pattern changes and passed on to the next generation, so that the offspring of male reproductive system critical role in the development of imprinted genes imbalances, and eventually lead to producing offspring cryptorchidism. This may be an important mechanism of reproductive system damage.

Purpose: We investigated the efficacy and safety of high-dose vitamin D supplementation (VDS) plus standard urotherapy (SU) in managing overactive bladder dry in children. Materials and Methods: A 3-arm, randomized clinical trial was performed at an academic center in China between January 2023 and June 2023. Eligible patients (n[303) were randomized to receive 8 weeks of high-dose VDS (vitamin D3 drops encapsulated as soft capsules, 2400 IU/d) plus SU (VDS D SU group; n[100), solifenacin (5-10 mg/d) plus SU (SOL D SU group; n[102), or SU alone (SU group; n[101). Reduction in voiding frequency was the primary outcome. Secondary outcomes encompassed improvement in urgency, nocturia, quality of life score, pediatric lower urinary tract symptom score, and participant satisfaction. Treatment-emergent adverse events were recorded within each group. Results: Participants had a median age of 82.0 months and their baseline mean vitamin D level was 22.64 ng/mL. The VDS D SU group showed greater improvements in voids/d than the SOLDSU group (median difference 3.0; 95% CI, 2.0 to 3.5; P < .001) and the SU group (median difference 4.0; 95% CI, 3.0 to 5.0; P < .001) after intervention. The VDSD SU group also showed the greatest improvement in quality of life and pediatric lower urinary tract symptom scores. Patient satisfaction was similar between the SOLDSU and SU groups. The VDSDSU group did not exhibit a heightened risk of treatment-emergent adverse events compared to the other groups. Conclusions: High-dose VDS plus SU was effective and well-tolerated in managing overactive bladder dry in children, suggesting its potential as a novel therapeutic option for this population. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 3-year-old girl who was admitted to a hospital for complaints of bilateral Wilm's tumor in the abdomen. The patient then underwent ultrasonic examination which revealed a tumor in her right and left kidneys. The patient was then subjected to a preoperative chemotherapy and an ultrasonic examination for monitoring.

Read-across, i.e., filling toxicological data gaps by relating to similar chemicals for which test data are available, is usually done based on chemical similarity. Besides structure and physico-chemical properties, biological similarity based on biological data adds extra strength to this process. In the simplest case, chemically similar substances also show similar test results in relevant in vitro assays. This is a well-established method for the read-across of, e.g., genotoxicity assays. Larger datasets of biological and toxicological properties of hundreds and thousands of substances are becoming available, enabling big data approaches in read-across studies. In the context of developing Good Read-Across Practice guidance, a number of case studies using various big data sources were evaluated to assess the contribution of biological data to enriching read-across. An example is given for the US EPA's ToxCast dataset which allows read-across for high quality uterotrophic assays for estrogenic endocrine disruption. Similarly, an example is given for REACH registration data that enhances read-across for acute toxicity studies. A different approach is taken using omics data to establish biological similarity: Examples are given for in vitro stem cell models and short-term in vivo repeated dose studies in rats used to support read-across and category formation. These preliminary biological data-driven read-across studies show the way towards the generation of new read-across approaches that can inform chemical safety assessment. [ABSTRACT FROM AUTHOR]

This paper describes a rapid method to determine aceglutamide (ACE) and oxiracetam (OXI) present in an injection formulation using reversed-phase high-performance liquid chromatography. The method was validated with respect to suitability, linearity, accuracy, precision and robustness. Chromatography was carried out on an Elite SinoChrom ODS-BP C18 (5 μm, 250 × 4.60 mm) column with an isocratic mobile phase composed of methanol-phosphate buffer (pH 3.0) in the ratio of 5:95, v/v, at a flow rate of 1.0 mL/min. Detectionwas carried out using a UV-PDA detector at 210 nm. The linearity range for ACE and OXIwere 10-500 and 10-300 mg/mL, respectively. The relative standard deviations for replicate measurements were always <2%. [ABSTRACT FROM AUTHOR]

Objective To describe 19 years of clinical experience managing pediatric patients with testicular yolk sac tumors at the Chongqing Medical University Affiliated Children's Hospital. Methods This study involved a retrospective review of the records of 61 pediatric patients who presented with testicular yolk sac tumor at our institution between 1995 and 2014. Results All patients presented with a painless scrotal mass. Serum alpha-fetoprotein (AFP) levels were elevated (n = 15). Ultrasonography identified the yolk sac tumors as solid masses. Color Doppler flow imaging showed rich blood flow inside and around the masses in 84.8% cases. X-ray of the scrotum showed no intrascrotal calcification (n = 38). Inguinal orchiectomy was performed in 60 patients, one case was treated with testis-sparing surgery. In 11 cases, radical dissection of the inguinal lymph nodes was performed. Histological analysis showed pathologies typical of yolk sac tumor including microcapsule and reticular structures, gland tube-gland bubble structures, an embryo sinus structure, and papillary structures. All patients received postoperative chemotherapy. Serum AFP levels returned to normal 1 to 2 months after surgery. No patients treated with surgery in our hospital relapsed. Conclusion Testicular yolk sac tumor presents as a painless scrotal mass, increased serum AFP levels, and a solid mass on ultrasound. Chest radiography and abdominal ultrasound should be used to accurately stage the tumor. We advocate for inguinal orchiectomy for Stage I disease and postoperative chemotherapy to prevent recurrence in the ipsilateral or contralateral testis. [ABSTRACT FROM AUTHOR]

Two monofunctional platinum(ii) complexes, cis-[PtL(NH3)2Cl]NO3(1) and cis-[PtL′(NH3)2Cl]NO3(2) {L = N-methyl-7-nitro-N-(2-(pyridin-2-yl)ethyl)benzo[c][1,2,5]-oxadiazol-4-amine, L′ = 7-nitro-N-(2-(pyridin-2-yl)ethyl)benzo[c][1,2,5] oxadiazol-4-amine}, have been synthesized and characterized. The X-ray single crystal structure of complex 1shows that platinum(ii) is coordinated in a square-planar geometry with a [PtN3Cl] setting. Fluorescence profiles of the complexes show that complex 1is more suitable for cellular imaging than complex 2. The cellular uptake and distribution of complex 1in the human cervical cancer HeLa cells were studied using confocal microscopy. Complex 1enters the cells slowly, induces cytoplasmic vacuolations, and accumulates in the nucleoli. These results suggest that monofunctional platinum(ii) complexes can stimulate tumour cells to undergo a nonapoptotic death process, which is distinct from the apoptosis induced by cisplatin. [ABSTRACT FROM AUTHOR]

This study investigated epigenetic (specifically, DNA methylation) changes and their impact on gene expression in testes induced by maternal exposure to Di-2-(ethylhexyl) phthalate (DEHP) in mice. Testicular dysgenesis syndrome was induced in fetuses and pups by maternal exposure to DEHP at 500 mg/kg/d, and testes were excised for analysis on gestation day (GD) 19 and postnatal days (PNDs) 3, 21, 56, and 90. High-performance liquid chromatography (HPLC) was performed to analyze DNA methylation status, and expression levels of the DNA methyltransferases were examined by quantitative real-time polymerase chain reaction (qPCR). Testis-specific gene, insulin-like hormone 3 (Insl3), and testosterone production were also detected. DEHP significantly increased DNA methylation levels on GD 19 and PND 3 (P < .05 and P < .05) but not on PNDs 21, 56, and 90. DEHP also significantly increased the expression of DNA methyltransferases. For DNA methyltransferase 1, the difference was not significant on PND 21, and DNA methyltransferase 3a and 3b returned to normal levels on PND 56. Fetal testes were a main target for DEHP as evidenced by a reduction in Insl3 expression and testosterone production. Effects of DEHP on Insl3 expression continued until PND 21. The DEHP-induced suppression of testosterone had not recovered on PND 56. Changes in DNA methylation may play an important role in abnormal testicular function caused by environmental factors such as maternal exposure to DEHP, which may be a mechanism of DEHP-mediated testicular toxicity. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyse epigenetic (specifically, DNA methylation) change in testes induced by maternal exposure to di-2-(ethylhexyl) phthalate (DEHP) in mice. Testicular dysgenesis syndrome was induced in foetuses by maternal exposure to DEHP. High-performance liquid chromatography was performed to analyse DNA methylation status, and expression levels of the DNA methyltransferases were examined by quantitative real-time polymerase chain reaction and western blotting. DEHP significantly had more than 10% relative increase in the global DNA methylation and also increased DNA methyltransferases’ expression. Changes in DNA methylation may play an important role in abnormal testicular function caused by environmental factors such as maternal exposure to DEHP, which may be one possible mechanism of DEHP-mediated testicular toxicity. [ABSTRACT FROM AUTHOR]

The biological fluorescent distribution of a model antitumor monofunctional platinum(II) complex bearing a 7-nitro-2,1,3-benzoxadiazole fluorophore can be visualized in breast carcinoma MCF-7 cells, pulmonary carcinoma A549 cells, kidney epithelial 293T cells, and zebrafish larva. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses a case report of a two-year-old boy with hydronephrosis who underwent right internal jugular venous catheter placement.

Respiratory syncytial virus (RSV) is the most important cause of severe, lower respiratory tract infections in infants, and RSV infections have been associated with chronic wheezing and asthma during childhood. However, the mechanism of RSV-induced airway inflammation and airway hyperresponsiveness (AHR) is poorly understood. Furthermore, there are presently neither effective vaccines nor drugs available for the prevention or treatment of RSV infections. In this study, we investigated the effect of the plant extract resveratrol as a means of preventing airway inflammation and attenuating RSV-induced AHR. Our data showed that resveratrol reduced RSV lung titers and the number of infiltrating lymphocytes present in bronchoalveolar lavage fluid (BALF) and reduced inflammation. Furthermore, resveratrol attenuated airway responses to methacholine following RSV infection and significantly decreased gamma interferon (IFN-γ) levels in BALF of RSV-infected mice. Data presented in this report demonstrated that resveratrol controlled Toll-like receptor 3 (TLR3) expression, inhibited the TRIF signaling pathway, and induced M2 receptor expression following RSV infection. These data support a role for the use of resveratrol as a means of reducing IFN-γ levels associated with RSV-mediated airway inflammation and AHR, which may be mediated via TLR3 signaling. [ABSTRACT FROM AUTHOR]