Renal-on-Chip Microfluidic Platform with a Force-Sensitive Resistor (ROC-FS) for Molecular Pathogenesis Analysis of Hydronephrosis.

Hydronephrosis is one of the most common diseases in urology. However, due to the difficulties in clinical trials and the lack of reliable in vitro platforms, the surgical indicators are not clear. Herein, the renal-on-chip with a force-sensitive resistor microfluidic platform was established to simulate the state of hydronephrosis. Cell counting kit-8 (CCK-8) and tight junction protein claudin-2 were detected on a renal-on-chip microfluidic platform with a force-sensitive resistor (ROC-FS). The results indicated that the ROC-FS had normal physiological functions and the cell viability on ROC-FS declined to around 40% after 48 h of hydronephrosis-simulated treatment. In addition, proteomics analysis of 15 clinical ureteropelvic junction obstruction (UPJO) samples showed that compared with normal children, a total of 50 common proteins were differentially expressed in UPJO children (P < 0.05, |log2fold change| ≥ 1). Metabolomic analysis of 39 clinical UPJO samples showed that a total of 241 metabolisms were dysregulated. Subsequent immunofluorescence and enzyme-linked immunosorbent assay (ELISA) analysis using ROC-FS were performed to identify the clinical multi-omics results for screening. All results pointed out that the TGF-ß-related signaling pathways and arginine-related metabolism signaling pathways were dysregulated and α-SMA, AGT, and AGA might be the potential biomarkers of hydronephrosis. In addition, correlation analysis of AGT and KLK1 with differential renal function (DRF) from clinical samples indicated good correlation coefficients (R2 0.923, 0.8742, 0.6412, and 0.8347). This demonstrates the state of hydronephrosis could be significantly correlated with the biomarkers. These findings could provide a reliable reference for determining surgical biomarkers clinically, and ROC could be further used in the analysis of other kidney diseases.

Association of neural tube defects with congenital abnormalities of the urogenital system in a Chinese cohort.

BACKGROUND: This study aimed to retrospectively analyze the correlation between congenital abnormality of the urogenital system and various factors in children with neural tube defects (NTDs). METHODS: A total of 190 children with congenital NTDs, who were admitted to a hospital from May 2013 to May 2018, were included into the present study. All admitted children with congenital NTDs were carried out routine abdominal B-ultrasound examinations to determine the malformations of the abdominal organs, including the urinary system. Children with a B-ultrasound result of suspected and unsure malformation underwent intravenous pyelography (IVP) and voiding cysto-urethrography (VCU), and this was further confirmed by the CT results. RESULTS: The incidence of urogenital malformation was 12.1% (23/190) in children with congenital NTDs. For the 23 children with urogenital malformations, most of these children had no definite urinary system symptoms, while some of these children had multiple incidences of urinary system infections. CONCLUSIONS: Congenital NTDs are often combined with urogenital malformations, if not specifically searched these may be overlooked. The early detection of these malformations is beneficial to reduce the risk of operation and improve the prognosis.

Identification of 8 novel gene variants in primary hyperoxaluria in 21 Chinese children with urinary stones.

PURPOSE: We analyzed primary hyperoxaluria (PH) genotype and phenotype in Chinese children. Vitamin B6 response in the patients with genetically confirmed PH1 was also studied. METHODS: We, respectively, analyzed 80 children with urinary stones. Sixty-four children were diagnosed with hyperoxaluria. Twenty-one children consented to genetic evaluation (targeted gene panel-based and whole-exome sequencing), and DNA was obtained from the children and both the parents. RESULTS: PH accounted for 57.1% (12/21) of hyperoxaluria cases. We reported 12 PH cases, including 5 PH1, 1 PH2, and 6 PH3 cases; 2 novel mutations in AGXT and GRHPR each and 4 HOGA1 mutations were identified. The mutations in AGXT and GRHPR were c0.1161C>A and c0.551C>A, and c0.370C>T and c0.864_865delTG, respectively. Four HOGA1 mutations, c0.290G>A, c0.110G>A, c0.554C>T and c0.834_834 + 1delinsTT, were not reported previously. The average urine Ox 24 level in the PH patients was 0.91 mmol/1.73 m2. Moreover, the average urine Ox 24 level in the PH1 patients (1.07 mmol/1.73 m2) was higher than that in the PH2 and PH3 patients (0.73 mmol/1.73 m2 and 0.71 mmol/1.73 m2, respectively). The eGFR of the PH1 patients (76.86 mL/min) was lower than that of the PH2 and PH3 patients (132 mL/min and 136 mL/min, respectively). CONCLUSIONS: PH incidence was higher than the reported PH incidence in children with urinary stones. Hence, we suggested that genetic examination was necessary for all the children with hyperoxaluria. These novel mutations broaden the range of known gene mutations in PH.

Nine novel HOGA1 gene mutations identified in primary hyperoxaluria type 3 and distinct clinical and biochemical characteristics in Chinese children.

BACKGROUND: Primary hyperoxaluria type 3 (PH3) is characterized by mutations in the 4-hydroxy-2-oxoglutarate aldolase (HOGA1) gene. PH3 patients are thought to present with a less severe phenotype than PH1 and PH2 patients. However, the clinical characteristics of PH3 patients have yet to be defined in sufficient detail. The aims of this study were to report HOGA1 mutations of PH3 in Chinese children, and to analyze the genotype and clinical characteristics of these PH3 patients. METHODS: Genetic analysis (targeted gene panel-based and/or whole-exome sequencing) of HOGA1 was performed in 52 patients with a high suspicion of PH3, and DNA was obtained from the patient and both the parents. The clinical, biochemical, and genetic data of these 12 patients identified with HOGA1 mutations were subsequently retrospectively reviewed. RESULTS: These 12 patients were identified with HOGA1 mutation. The median onset of clinical symptoms was 18.25 (range 5-38) months. In total, 14 different mutations were identified including 9 novel mutations in these 12 patients with PH3. All of these 12 patients initially presented with urolithiasis, and 3 patients among them comorbid urinary tract infection (UTI) as another initial symptom. Ten patients experienced hyperoxaluria (average oxalate 0.77 mmol/1.73 m2/24h). In contrast, urine calcium excretion was normal in 8 patients and 2 patients with hypercalciuria (urine calcium > 4 mg/kg/24 h). At the time of diagnosis, estimated GFR was 155.6 ml/min per 1.73 m2, and at last follow-up time (17.3 months later from diagnosis on average), estimated GFR was 157.5 ml/min per 1.73 m2. To date, none of the patients has impaired renal function based on and progressed to ESRD. CONCLUSIONS: We found that PH3 was significantly diagnosed in our urolithiasis patients during childhood. Nine novel HOGA1 mutations were identified in association with PH3, which provide a first-line investigation in Chinese PH3 patients. The eGFR was normal in all children with PH3. This finding is in contrast to the early impairment of renal function in PH1 and PH2.

Predictive Factors of Contralateral Operation after Initial Pyeloplasty in Children with Antenatally Detected Bilateral Hydronephrosis Due to Ureteropelvic Junction Obstruction.

OBJECTIVES: This study was performed to analyze the predictive factors of a contralateral operation after initial pyeloplasty in patients with antenatally detected bilateral ureteropelvic junction obstruction. METHODS: Patients with prenatally diagnosed bilateral ureteropelvic junction obstruction who underwent initial pyeloplasty (aged <12 months at initial pyeloplasty) were offered to participate in the study. Patients were recruited from January 2012 to December 2015. The anteroposterior renal pelvic diameter, parenchymal thickness, and calyceal dilatation were evaluated. Predictive factors of contralateral pyeloplasty after initial unilateral pyeloplasty were also examined. RESULTS: In total, 82 patients were included in the study (mean age, 2.8 months). Among all patients who underwent initial pyeloplasty, additional contralateral pyeloplasty was required in 11 patients (13.4%). The outcome of contralateral hydronephrosis was assessed as resolution, persistence, or surgery. The median anteroposterior renal pelvic diameter and calyceal dilatation were significantly different among the groups (p < 0.001). Calyceal dilatation of ≥10 mm and a calyceal dilatation/parenchymal thickness ratio of ≥5 strongly suggested the likelihood of a contralateral operation. CONCLUSIONS: In most patients with bilateral ureteropelvic junction obstruction, improvement or resolution of contralateral hydronephrosis following initial unilateral pyeloplasty can be expected. Patients with contralateral calyceal dilatation >10 mm and the calyceal dilatation/parenchymal thickness ratio >5 are at higher risk of surgery.

Curcumin improves tendon healing in rats: a histological, biochemical, and functional evaluation.

Curcumin, a compound extracted from the roots of Zingiberaceae, has been proposed as a treatment for tissue injury but studies are yet to be done on its effect on tendon healing. Therefore, we performed a series of experiments to test our hypothesis that curcumin has positive effects on tendon repair. Patellar tendon window defect was created in Sprague-Dawley rats and these were divided into two groups: (i) control and (ii) curcumin-treated. Curcumin (100 mg/kg body weight) was applied by oral gavage. Its potential for promoting tendon healing was assessed by histological evaluation, mRNA expression of tenocyte-related genes, malondialdehyde (MDA) levels, manganese-dependent superoxide dismutase (MnSOD) activity, quantification of hydroxyproline (HOPro), and biomechanical testing. In this tendon injury model, curcumin significantly improved the healing properties as evidenced by extensive deposition of well-organized collagen fibers, decreased MDA levels, and increase in the biomechanical properties and MnSOD activity of the regenerated tendon tissues. The current study showed that curcumin can improve the quality of tendon rupture healing, and thus represents a promising strategy in the management of injured tendon tissue.

Combined effect of ligament stem cells and umbilical-cord-blood-derived CD34+ cells on ligament healing.

Transplantation of ligament-tissue-derived stem cells has become a promising approach in the repair of injured ligament. Neovascularization plays an important role in ligament healing and remodeling. Recently, human umbilical-cord-blood-derived CD34+ cells have been reported to contribute to neoangiogenesis. Therefore, we performed a series of experiments to test our hypothesis that the combination of medial collateral ligament stem cells (MCL-SCs) and umbilical-cord-blood-derived CD34+ cells has synergistic effects on tendon healing. MCL-SCs and umbilical-cord-blood-derived CD34+ cells were isolated and cultured. Rat MCL injury was treated by MCL-SCs and/or CD34+ cells. Response to the cell therapy was assessed by gross observation, histological evaluation and biomechanical testing at 2 and 4 weeks after each treatment. Although each cell therapy group induced macroscopic and morphological recovery in healing MCLs, the combined use of MCL-SCs/CD34+ cells led to further improvement in healing quality. Capillary density was significantly higher in the CD34+ cell transplantation groups than in the other groups at week 2. Biomechanical testing demonstrated that the failure load of the healing ligament was greatest in the combination therapy group. The combination of MCL-SCs and CD34+ cells as a cell therapeutic thus enhances healing and restores biomechanical function toward normal after MCL injury. The findings obtained in our study suggest that the combination of MCL-SCs and CD34+ cells transplantation represents a promising strategy for ligament injury.

Diacylglycerol kinase κ (DGKK) variants and hypospadias in Han Chinese: association and meta-analysis.

OBJECTIVE: To investigate whether diacylglycerol kinase κ (DGKK) is a susceptibility gene for hypospadias in the Han Chinese population as has been suggested by previous publications. PATIENTS SUBJECTS AND METHODS: A case-control study involving 466 patients with hypospadias and 402 healthy subjects was conducted to assess the relationship between DGKK single nucleotide polymorphisms (SNPs) and hypospadias risk in the Han Chinese population. The 466 hypospadias patients were further divided into mild, moderate and severe subgroups for analysis. RESULTS: Six SNPs (rs1934179, rs4143304, rs9969978, rs1934188, rs4826632 and rs4599945) were marginally associated with mild and moderate hypospadias [odds ratios (ORs) > 1, P = 0.05 to P < 0.1), whereas no significant relationship was seen with the severe cases (ORs >1, P > 0.1). After correcting for multiple testing, it was determined that neither individual SNPs nor individual haplotypes were associated with hypospadias. To evaluate this relationship in multiple populations, we performed a meta-analysis on six SNPs, using combined data from our present results and those of previous studies of different races (including 1966 patients and 2492 controls). Six SNPs (rs1934179, rs4143304, rs9969978, rs1934188, rs7063116 and rs1934190) were significantly associated with mild/moderate hypospadias (ORs >1, P < 0.05), and rs1934179 was significantly associated with severe hypospadias (OR > 1, P < 0.05). CONCLUSIONS: DGKK gene variants do not appear to play a major role in hypospadias susceptibility in the Chinese Han population. Our meta-analysis supports the hypothesis that DGKK is a common risk gene for hypospadias, particularly in cases of mild or moderate hypospadias in Caucasian populations.

[Relationship between anogenital distance and cryptorchidism in human newborns].

OBJECTIVE: To explore the relation of the anogenital distance (AGD) with cryptorchidism in male newborns. METHODS: This study included 350 male infants delivered in two community hospitals between September 2013 and September 2014. Within 24 hours after birth, a pediatric surgeon measured the AGD of the neonates and determined whether they had cryptorchidism. According to the testicular position, we divided the undescended testes into three types: upper scrotal, inguinal, and non-palpable. RESULTS: Totally 39 cases of cryptorchidism were found in the 350 newborns. The AGD of the cryptorchidism infants was significantly shorter than that of the normal neonates ([2.01 ± 0.22] vs [2.35 ± 0.19] cm, P < 0.01), and statistically significant differences remained even when preterm and low birth-weight infants were excluded ([2.32 ± 0.14] vs [2.06 ± 0.19] cm; (2.37 ± 0.17) cm vs (2.12 ± 0.12) cm, all P < 0.01). The newborns with higher-position cryptorchidism had a shorter AGD, though with no significant difference (F = 0.434, P > 0.05). No significant differences were observed in the AGD between unilateral and bilateral cryptorchidism ([1.96 ± 0.13] vs [2.02 ± 0.17] cm, P > 0.05). CONCLUSION: Shorter AGD is associated with a higher incidence of cryptorchidism in male newborns. AGD could serve as a potential biomarker for disruption of androgen action during the male programming window period.

Noncystoscopic Removal of Double-J Stent in Women: Feasibility and Safety.

OBJECTIVE: To evaluate the feasibility and safety of a simple noncystoscopic method previously applied in children for removing double-J stents applied in women by comparing the hospitalization time, operation time, costs, complications, and success rate. METHODS: One hundred eighty women who underwent either cystoscopic or noncystoscopic double-J stent removal in a randomized manner. They were randomly assigned 1:1 to groups of cystoscopic double-J stent removal (n = 90) or noncystoscopic double-J stent removal (n = 90). The age ranged from 19 to 72years. After the removal of the double-J stent, the operation time, costs, complications, and success rate were compared between the two groups. RESULTS: The operation time of the noncystoscopic group was lower than that of the cystoscopic group (6.0(5.0,7.0) minutes vs 2.0(2.0,3.0) minutes, P < .001). The hospitalization costs of the noncystoscopic group were significantly shorter than that of the cystoscopic group (1361.2(1331.4,1379.2) Yuan vs 873.9(868.5,896.1) Yuan, P < .001). There were no complications such as infection and massive bleeding in the two groups during and after the operation. Most noncystoscopic double-J stent removal can succeed in less than three attempts (88/90). All patients in the noncystoscopic group used this technique to remove the double-J stent. CONCLUSION: Noncystoscopic removal of double-J stent has the advantages of short operation time and low hospitalization costs. It is a safe and feasible minimally invasive method to replace cystoscopic removal of the double-J stent.

Pseudoduplication of the external genitalia.

A 1-year-old boy was referred to our department with a pseudoduplication of the external genitalia present since birth. At surgery, we performed a complete excision of the mass through a "Y-type" perineal incision. The boy was taken to our department for a regular physical examination 2 years after the surgery. The appearance of the perineal region was satisfactory.

Cancer Stem Cells in Tumours of the Central Nervous System in Children: A Comprehensive Review.

Cancer stem cells (CSCs) are a subgroup of cells found in various kinds of tumours with stem cell characteristics, such as self-renewal, induced differentiation, and tumourigenicity. The existence of CSCs is regarded as a major source of tumour recurrence, metastasis, and resistance to conventional chemotherapy and radiation treatment. Tumours of the central nervous system (CNS) are the most common solid tumours in children, which have many different types including highly malignant embryonal tumours and midline gliomas, and low-grade gliomas with favourable prognoses. Stem cells from the CNS tumours have been largely found and reported by researchers in the last decade and their roles in tumour biology have been deeply studied. However, the cross-talk of CSCs among different CNS tumour types and their clinical impacts have been rarely discussed. This article comprehensively reviews the achievements in research on CSCs in paediatric CNS tumours. Biological functions, diagnostic values, and therapeutic perspectives are reviewed in detail. Further investigations into CSCs are warranted to improve the clinical practice in treating children with CNS tumours.

OSCA-finder: Redefining the assay of kidney disease diagnostic through metabolomics and deep learning.

Liquid chromatography-mass spectrometry (LC-MS) is a platform for urine and blood sample analysis. However, the high variability in the urine sample reduced the confidence of metabolite identification. Therefore, pre and post-calibration operations are inevitable to ensure an accurate urine biomarker analysis. In this study, the phenomenon of a higher creatinine concentration variable in ureteropelvic junction obstruction (UPJO) patient urine samples than in healthy people was revealed, indicating the urine biomarker discovery of UPJO patients is not adapted to the creatinine calibrate strategy. Therefore, we proposed a pipeline "OSCA-Finder" to reshape the urine biomarker analysis. First, to ensure a more stable peak shape and total ion chromatography, we applied the product of osmotic pressure and injection volume as a calibration principle and integrated it with an online mixer dilution. Therefore, we obtained the most peaks and identified more metabolites in a urine sample with peak area group CV<30%. A data-enhanced strategy was applied to reduce the overfit while training a neural network binary classifier with an accuracy of 99.9%. Finally, seven accurate urine biomarkers combined with a binary classifier were applied to distinguish UPJO patients from healthy people. The results show that the UPJO diagnostic strategy based on urine osmotic pressure calibration has more potential than ordinary strategies.

Assessment of cancer-related signaling pathways in responses to polystyrene nanoplastics via a kidney-testis microfluidic platform (KTP).

As a new type of environmental pollutants, micro/nano plastics (MPs/NPs) derived from plastic products are commonly contact in daily life and lead to some serious health issues. The toxicity effects of MPs/NPs on the human body have aroused wide concerns. Although MPs/NPs have been reported to be transmitted into the kidney and reproductive organs, the molecular mechanisms of MPs/NPs toxicity remain unclear due to the lack of a physiologically relevant organ-organ linking platform in vitro. Here, we present a kidney-testis microfluidic platform (KTP) with NPs exposure that enables the communication of kidney and testis chambers and reproduces endothelium-linked chambers to simulate the state in vivo. The function of KTP was assessed by cell counting kit (CCK-8), tight junction protein claudin-2 and glucose consumption. Results revealed that MPs/NPs entered the kidney and testis via endocytosis. Immunofluorescence and ELISA analysis were performed on KTP at 200 µg/mL PS-NP to identify the dysregulated proteins on cancer-related signaling pathways, including the MAPK signaling pathway (RTK, RAS, ERK, JNK, P38, NRF2, TNF-α, and TNF-α-R) and the PI3K-AKT signaling pathway (PI3K, AKT, MDM2, P53, and ΒΑD). This multi-organ platform (KTP) contributes to clarifying cancer pathways triggered by MPs/NPs exposure and provides a promising method for assessing diseases induced by environmental pollutants.

Matrix-assisted laser desorption/ionization mass spectrometric imaging the spatial distribution of biodegradable vascular stents using a self-made semi-quantitative target plate.

In recent years, the development and optimization of biodegradable coronary stents have become the research focus of many medical device manufacturers and scientific research institutions since they can be completely degraded and absorbed, and they restore vascular function. However, there is a lack of in situ quantification of these stents spatially in tissue in vivo. In this study, matrix-assisted laser desorption/ionization (MALDI) Fourier transform ion cyclotron resonance (FT ICR) and time-of-flight (TOF) mass spectrometric imaging (MSI) were used to analyze the time-dependent distributions of a biodegradable vascular scaffold, which consisted of copolymers of lactic acid and glycolic acid (PLGA) and its degradation products in cross-sections and longitudinal sections of blood vessels. The MALDI-MSI methods for analyzing the distribution of PLGA and its derivatives in vivo were established by optimizing the conditions of sample pretreatment and mass spectrometry (MS). In order to semi-quantify the contents of PLGA degradation products in blood vessels, self-made stainless-steel and indium tin oxide (ITO) target plates were developed to compare and establish the standard curves for semi-quantitative analysis. The target plate can be placed on the target carrier of MS simultaneously with the conductive slide, which can simultaneously carry out vapor deposition or spray on the substrate, to ensure the parallelism of the pretreatment experiments between the standards and the actual vascular samples. The proposed method provided a powerful tool for evaluating the distributions and degradation process of biological stent materials in the coronary artery, as well as provided technical support for the research and development of degradable biological stents and product optimization.

Single-port laparoscopy-assisted trans-scrotal hernia sac ligation for pediatric male inguinal hernia.

Objective: We report the introduction of a novel single-port laparoscopic-assisted trans-scrotal hernia sac ligation (LAT-HSL) technique for the treatment of inguinal hernias in pediatric males. In this article, we describe the LAT-HSL technique and the outcomes. Methods: Twenty-five male children with confirmed unilateral inguinal hernia who underwent surgical treatment from January 2020 to September 2021 were selected for this study. All children underwent surgical treatment with LAT-HSL, and the operative time, hospital stay, and postoperative results and complications were recorded. Results: All 25 cases underwent LAT-HSL with minimal perioperative complications, and all children were successfully discharged from the hospital postoperatively. At the postoperative follow-up, there was no retraction or atrophy of the testes, no incisional infection, no chronic pain, no urinary retention, and no recurrent hernias. Conclusion: Single-port LAT-HSL allows for rapid and accurate localization of the extra-abdominal hernia sac. The method is safe, easy to perform, and adaptable. Additionally, the scar is hidden, and the operation time is short.

[Urine metabolomics analysis based on ultra performance liquid chromatography-high resolution mass spectrometry combined with osmolality calibration sample concentration variability].

Urine is an important source of biomolecular information for metabolomic studies. However, the acquisition of high-quality metabolomic datasets or reliable biomarkers from urine is difficult owing to the large variations in the concentrations of endogenous metabolites in the biofluid, which are caused by diverse factors such as water consumption, drugs, and diseases. Thus, normalization or calibration is essential in urine metabolomics for eliminating such deviations. The urine osmolality (Π), which is a direct measure of the total urinary solute concentration and is not affected by circadian rhythms, diet, gender, and age, is often considered the gold standard for estimation of the urine concentration. In this study, a pre-data acquisition calibration strategy based on osmolality was investigated for its feasibility to overcome sample concentration variability. Before data acquisition, the product of the osmolality×injection volume of all samples was set to be equivalent through the uses of a customized injection volume or dilution. After ultra performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) analysis of the sample, the raw dataset was normalized to the total ion abundance or total useful MS signals (MSTUS) to achieve further calibration. The osmolality of each urine sample was determined with a freezing-point depression osmometer. For the instrumental analysis, a Vanquish UPLC system coupled to a Q-Exactive Plus HRMS device was used for metabolite analysis and accurate mass measurement. Full-scan mass spectra were acquired in the range of m/z 60-900, and the MS/MS experiments were conducted in "Top5" data-dependent mode. A Waters UPLC column (100 mm×2.1 mm, 1.8 µm) was used for chromatography separation. The raw data were imported into Progenesis QI software for peak picking, alignment, deconvolution, and normalization. SIMCA-P software was used for the principal component analysis (PCA) and orthogonal partial least-squares discrimination analysis (OPLS-DA). This strategy was first applied to sequentially diluted urine samples, where three frequently used normalization methods were compared. In the identical injection volume experiment, the points were scattered and showed relevant distribution according to the dilution multiple in the plot of PCA scores. There was little improvement after normalization to either the total ion abundance or MSTUS. In the customized injection volume experiment, the urine samples derived from the same source showed ideal clustering. With total ion abundance and MSTUS normalization, the dataset was further improved in the PCA model fitting and prediction. As a result, there were more peaks with a peak area RSD of <30%, which indicated better parallelism. The diluted urine solutions had higher Spearman's coefficient values with their sample source than those without calibration, which suggested less intra-group differences. The strategy was further validated using data from a metabolomic study of children with congenital hydronephrosis and healthy controls. As a concentration estimator, osmolality showed better linear correlation with the mass signal and was less influenced by physiological or pathological factors, thus obtaining broader application and more accurate results than creatinine. The concentration variability was effectively eliminated after customized dilution calibration and showed a more obvious clustering effect in the PCA score plot. The OPLS-DA-based statistical model used to identify discriminate metabolites was improved, with less chance of overfitting. In conclusion, the calibration strategy based on osmolality combined with total ion abundance or MSTUS normalization significantly overcame the problem of urine concentration variability, eliminated intra-group differences, and possessed better parallelism, thus giving better clustering effects in PCA or OPLS-DA and higher reliability of the statistical model. The results of this study provide guidance and a reference for future metabolomic studies on urine.

Corrigendum: The Application of External Ureteral Catheters in Children With Acute Kidney Injury Caused by Ceftriaxone-Induced Urolithiasis.

[This corrects the article DOI: 10.3389/fped.2020.00200.].

The Application of External Ureteral Catheters in Children With Acute Kidney Injury Caused by Ceftriaxone-Induced Urolithiasis.

Objective: To evaluate our use of external ureteral catheters in children with acute kidney injury (AKI) resulting from ceftriaxone-induced urolithiasis. Methods: From July 2010 to June 2015, a series of 15 children, including 12 males and 3 females, were referred to our department. All of them were diagnosed of post-renal AKI and underwent emergent hospitalization. Evaluation of serum electrolytes, creatinine (Cr), blood urea nitrogen (BUN), complete blood count, and blood gas analysis were completed in each child both before they were admitted, and again after surgery. Bilateral externalized ureteral catheters were placed cystoscopically in each of these patients. The composition of collected calculi was analyzed by infrared spectrography. Results: Bilateral externalized ureteral catheters were placed successfully in all patients. There were no procedure-related complications. Two days after catheter placement, the levels of serum Cr and BUN had improved in all patients, and these levels were noted to be significantly lower than before catheterization (P < 0.001). Infrared spectrography demonstrated that the primary composition of all calculi collected was ceftriaxone. No recurrent AKI or renal deterioration was detected during the follow-up which ranged from 3 to 8 years. Conclusions: These results show that short-term external ureteral catheters can be effectively utilized in children with AKI caused by ceftriaxone-induced urolithiasis. We recommend this procedure as a viable replacement to indwelling stents in patients with bilateral ureteral stones.

Maternal exposure to environmental endocrine disruptors during pregnancy is associated with pediatric germ cell tumors.

Environmental endocrine disruptors (EEDs) are natural or synthetic chemical compounds that interfere with normal endocrine function in both wildlife and humans. Previous studies have indicated that EEDs may contribute to oncogenesis. This study explores the relationship between EEDs and pediatric germ cell tumors (GCTs). A case-control study was conducted in 84 pediatric patients from 2014 to 2017, including 42 subjects with immature teratoma, yolk sac tumor, or germinoma, and 42 controls who experienced pneumonia or trauma. Serum PFASs, including PFBS, PFHpA, PFHxS, PFOA, PFOS, PFNA, PFDA, PFUA, PFOSA, and PFDoA, were measured in each subject, and their history of possible EED exposure was reviewed. Six of the 10 measured PFASs were significantly increased in the GCT group relative to the control group. With respect to lifestyle history, only PFHxS levels were statistically significantly associated with GCTs as determined by logistic regression analysis. The odds ratio for a 1 ng/L increase in PFHxS was 19.47 (95% CI: 4.20-90.26). Furthermore, in the GCT and control groups, both parental consumption of barbecued foods and hair dye use among parents were significantly correlated with elevated serum PFHxS levels (ρ = 0.383, 0.325 in the patient group and ρ = 0.370, 0.339 in the control group; p < 0.05). Our study confirmed that children with GCTs from our institute had relatively high serum levels of PFASs relative to those of tumor-free pediatric patients. Serum PFHxS levels were independently associated with germ cell tumor occurrence.