Phenotype expansion of variants affecting p38 MAPK signaling in hypospadias patients.

BACKGROUND: Hypospadias is a congenital anomaly of the male urogenital system. Genetics factors play an important role in its pathogenesis. To search for potential causal genes/variants for hypospadias, we performed exome sequencing in a pedigree with three patients across two generations and a cohort of 49 sporadic patients with hypospadias. RESULTS: A novel BRAF variant (NM_004333.6: c.362C > A) was found to co-segregate with the hypospadias phenotype in the disease pedigree. In cells overexpressing the BRAF mutant, the phosphorylation level of p38 MAPK was significantly increased as compared with the cells overexpressing the wild-type BRAF or RASopathy-related BRAF mutant. This variant further led to a reduced transcription level of the SRY gene, which is essential for the normal development of the male reproductive system. In the cohort of sporadic patients, we identified two additional variants in p38 MAPK signaling-related genes (TRIM67 and DAB2IP) potentially associated with hypospadias. CONCLUSION: Our study expands the phenotypic spectrum of variants affecting p38 MAPK signaling toward the involvement of hypospadias.

Vaginal tumours in childhood: a descriptive analysis from a large paediatric medical centre.

PURPOSE: Malignant tumours of the vagina are very rare in children. The purpose of this study was to retrospectively analyse the clinical presentation, treatment, and outcome of vaginal tumours in children treated in a single institution. METHODS: This study retrospectively analysed the clinical data of children diagnosed with vaginal malignant tumours who were admitted to the Beijing Children's Hospital of Capital Medical University from January 2007 to December 2020 and followed these patients to observe their prognoses and outcomes. RESULTS: During 13 years, a total of 33 children were included in this study, including 13 children with rhabdomyosarcoma and 20 children with endodermal sinus tumours. The average age at diagnosis was 20.4 months. The main clinical manifestations were vaginal bleeding and protruding masses. Of the 13 children with vaginal rhabdomyosarcoma, 12 were treated with multidrug chemotherapy combined with conservative tumour resection, and their tumours completely resolved; only one child underwent vaginectomy and hysterectomy. Twenty children with vaginal endodermal sinus received PEB chemotherapy. Among these patients, the tumour disappeared after chemotherapy in 12 children, and the remaining nodular tumour foci in 8 children were confirmed to be necrotic tissue by pathology. CONCLUSION: Our research confirms that chemotherapy combined with conservative surgical treatment is effective for treating children with vaginal malignancies.

Quantitative assessment of renal perfusion in children with UPJO by contrast enhanced ultrasound: A pilot study.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) is a new potential modality for the quantitative evaluation of the microvascular perfusion of a parenchymal organ. OBJECTIVE: To prospectively and quantitatively analyse the role of CEUS in evaluating renal perfusion for assessing renal function in children with ureteropelvic junction obstruction (UPJO). METHODS: The study protocol was approved by the local ethics committee, and written informed consent was obtained from the patients' parents or guardians. Ultrasonography, CEUS, and radioisotope renography were performed for 51 children (42 boys, 9 girls; mean age, 6.75 ± 4.14 years) with unilateral UPJO. The slope of the ascending curve (A), time to peak (TTP), peak intensity (PI), and area under the curve (AUC) were recorded during CEUS; quantitative data were calculated by QLab system (semiautomated border tracking, Philips Healthcare) software. Sensitivity and specificity values were determined for CEUS with respect to radioisotope renography. RESULTS: CEUS was used to evaluate 102 kidneys in 51 patients, for which the perfusion time-intensity curve (TIC) was determined. The TIC of renal cortical perfusion in all groups showed an asymmetrical single-peak curve, which could be clearly distinguished between the experimental group and the control group. Compared with the control group, the experimental group showed a markedly prolonged TTP but a significantly decreased A (P < 0.05). There was no significant correlation between the AUC, PI and differential renal function (DRF), but the correlation coefficient between TTP, A and DRF remained significant (p < 0.001).The receiver operating characteristic (ROC) curves drawn to differentiate DRF using the TTP value yielded an area under the ROC curve (AUROC) of 0.86. For a quantitative assessment of DRF less than 40% by CEUS, the sensitivity and specificity values were 92.86% and 76.14%, respectively. DISCUSSION: Unlike in previous studies, no significant difference in the AUC or PI was found between the control group and the experimental group in this study (P > 0.05). Renal blood perfusion could not be evaluated overall by CEUS. Parenchymal thinning may be considered a limitation to CEUS. CONCLUSIONS: This preliminary experience represents the first report of evaluating the diagnostic value of CEUS in assessing renal function in children with UPJO. CEUS is a highly sensitive, rapid, and cost-effective diagnostic imaging modality for detecting and monitoring renal function noninvasively.

Congenital midureteral stenosis in children: a 13-year retrospective study based on data from a large pediatric medical center.

BACKGROUND: Midureteral stenosis is very rare in children and can cause congenital hydronephrosis. We report our experience treating children with congenital midureteral stenosis at our center, focusing on the differences in preoperative diagnosis and treatment compared with other congenital obstructive uropathies. METHODS: We retrospectively reviewed the medical records of 26 children diagnosed with congenital midureteral stenosis at our center between January 2007 and December 2020, such as preoperative examination methods, intraoperative conditions, and postoperative follow-up results. RESULTS: Of the 1625 children treated surgically for ureteral narrowing, only 26 (1.6%) were diagnosed with midureteral stenosis, including 15 infants and 11 children. Eighteen (69.2%) were boys, 13 (50%) were affected on the left side, and 23 (88.5%) had isolated ureteral stenosis. Overall, 13 (50%) of the children presented with prenatal hydronephrosis, and 13 (50%) presented with abdominal pain or a mass. All the children had undergone urinary ultrasound and intravenous urography preoperatively; the diagnostic rate of ultrasound was 92.3%. Only 7 (26.9%) children had undergone pyelography. All the children had undergone surgery. The ureteral stenotic segment was less than 1 cm long in 25 (96.2)% of the children. The mean follow-up duration was 22 months (range: 6-50 months). One child developed anastomotic strictures. Urinary tract obstruction was relieved in the other children without long-term complications. CONCLUSIONS: Congenital midureteral stenosis is rare, accounting for 1.6% of all ureteral obstructions, and its diagnosis is crucial. Urinary ultrasound has a high diagnostic rate and should be the first choice for midureteral stenosis. Retrograde pyelography can be used when the diagnosis is difficult, but routine retrograde pyelography is not recommended. Congenital ureteral stenosis has a relatively short lesion range, largely within 1 cm. The treatment is mainly resection of the stenotic segment and end-to-end ureteral anastomosis, with a good prognosis.

Extrarenal Wilms tumor in children: A retrospective observational case series.

INTRODUCTION: Pediatric extrarenal Wilms tumor (ERWT) is rare. The diversity of clinical characteristics makes diagnosis, treatment and judging the prognosis difficult. Long-term follow-up outcomes and the possible prognostic factors of ERWT are still insufficient. OBJECTIVE: To identify the characteristics, therapeutic strategies and long-term results of pediatric ERWT. PATIENTS AND METHODS: All children with ERWT in our institution were retrospectively reviewed. The National Wilms Tumor Study (NWTS) system was used to evaluate tumor grade. RESULTS: Among the 876 patients with Wilms tumor in our institution between January 1986 and July 2018, 5 (0.57%) patients had ERWT. Of the 5 children with ERWT, the locations were the retroperitoneum in 3 patients (including 1 presacral) and the gubernaculum testis of an undescended testis and a duplicate sigmoid colon in 1 patient each. Two patients were stage II, and 3 patients were stage III. The three patients with larger tumor sizes had preoperative tumor rupture. In the long-term follow-up, ranging from 1.0 to 10.8 years, 3 patients had disease-free survival, and 2 patients with older age, a larger tumor size and preoperative tumor rupture had recurrence with metastasis, including 1 death. DISCUSSION: Wilms tumor extremely rarely originates outside the kidney. The current case series represents the first report of ERWT accompanied by a duplicate sigmoid colon. ERWT can coassociate with congenital gastrointestinal and genitourinary system anomalies, such as undescended testis and duplicate sigmoid colon, which provide clues to the preoperative diagnosis of ERWT. Deep and not easily palpated locations for the ERWT and older ages were associated with diagnosis delay, which can lead to enlargement of the tumor, an increased risk of preoperative tumor rupture and advancement of the tumor stage. Although only 3% of ERWT cases were metastatic according to previous reports, 2 of 5 patients (patients 1 and 4) with older age, larger tumor size and preoperative tumor rupture had recurrence and metastases in the current study. Thus, patients with poor prognoses often require aggressive combination treatments, and more attention is needed in terms of the recurrence, metastases and fatality of ERWT. CONCLUSION: ERWTs are rare tumors and can coassociate with congenital gastrointestinal and genitourinary system anomalies. The prognosis of ERWT is comparable to that of Wilms tumor located at normal anatomical sites.

Use of Acellular Dermal Matrix for Urethroplasty Coverage in Proximal Hypospadias Repair: a Pilot Study.

INTRODUCTION: The complication rates of proximal hypospadias, especially fistula, are much higher than those of distal hypospadias. Urethral coverage is an effective method for reducing fistulas. Acellular dermal matrix (ADM) has been shown to exhibit structural compatibility and biocompatibility, both of which promote tissue healing. METHODS: The present non-randomized study evaluated the efficiency, feasibility, and safety of using ADM for urethroplasty coverage in patients with proximal hypospadias. This prospective study enrolled 35 patients (age range 15-60 months) with proximal hypospadias who underwent operation between September 2018 and March 2019 at Beijing Children's Hospital (Beijing, China). Urethroplasties were performed by the transverse preputial island flap (TPIF) technique. ADM was applied and sutured over the urethroplasty as an additional covering layer. Patient outcomes were compared with those of 80 non-matched control patients with proximal hypospadias who underwent the same procedure, with dartos as a covering layer. RESULTS: During a median follow-up of 11.56 months (range 9-15 months), urethral fistula occurred in six patients (17.1%) in the ADM group and 28 patients (35%) in the dartos group. Superficial wound infection was observed in six patients (17.1%) in the ADM group and 10 patients (12.5%) in the dartos group. One patient in the ADM group had diverticulum, compared with five patients (6.25%) in the dartos group. Meatal stenosis and urethral stricture were observed in four patients (11.4%) in the ADM group and six patients (7.5%) in the dartos group; all of these complications were treated conservatively. No glans dehiscence was observed in either group. CONCLUSION: Use of ADM may be a safe and efficient covering technique to provide an additional coverage layer for proximal hypospadias repair, thereby reducing the incidence of fistula formation, especially among patients who have poor-quality covering materials.

The distribution of Preputial vessels in different severity of rat congenital hypospadias model: imaging study using micro-computerized tomography.

BACKGROUND: Micro-computerized tomography (micro-CT) is considered as an innovative non-invasive and high-resolution imaging technology. The current research aims to reconstruct the distribution of preputial vessels in different severity of rat congenital hypospadias model by micro-CT, and to provide an anatomic basis for the selection of preputial vessel pedicle flaps in surgery. METHODS: Pregnant rats were exposed to finasteride from gestational day 12 to 17. Depending on the position of the urethral meatus, the pups were divided into normal, mild hypospadias and severe hypospadias groups. Six months after birth, the preputial blood vessels were observed in vascular perfusion with Microfil (a silicone-based polymer) and scanned by micro-CT. CTvox and NRecon were utilized to reconstruct 3-dimentional (3D) images. A pathological analysis of the specimen was taken in order to determine the position of Microfil. RESULTS: The normal group and the mild hypospadias group had similar preputial image characteristics. At the junction of the inner and outer prepuce, the deep layer vessels of the superficial fascia were transversely distributed and formed a vascular ring-like structure. Among the severe hypospadias group, five had sufficient blood circulation while six had insufficient blood circulation. In sufficient blood circulation type, the ring-like vessels were found at the junction of the inner and outer prepuce similar to that of the normal and mild hypospadias group. However, only a small amount of capillary supply to this area in the insufficient type. CONCLUSION: The junction of the inner and outer prepuce with abundant blood circulation was suitable to be a vascular pedicle flap. The tubularized preputial island flaps were consistent with the ring-like vessels area, and the original blood supply was retained to the greatest extent.

Drone Detection and Pose Estimation Using Relational Graph Networks.

With the upsurge in use of Unmanned Aerial Vehicles (UAVs), drone detection and pose estimation by using optical sensors becomes an important research subject in cooperative flight and low-altitude security. The existing technology only obtains the position of the target UAV based on object detection methods. To achieve better adaptability and enhanced cooperative performance, the attitude information of the target drone becomes a key message to understand its state and intention, e.g., the acceleration of quadrotors. At present, most of the object 6D pose estimation algorithms depend on accurate pose annotation or a 3D target model, which costs a lot of human resource and is difficult to apply to non-cooperative targets. To overcome these problems, a quadrotor 6D pose estimation algorithm was proposed in this paper. It was based on keypoints detection (only need keypoints annotation), relational graph network and perspective-n-point (PnP) algorithm, which achieves state-of-the-art performance both in simulation and real scenario. In addition, the inference ability of our relational graph network to the keypoints of four motors was also evaluated. The accuracy and speed were improved significantly compared with the state-of-the-art keypoints detection algorithm.

Continuous composite finite-time convergent guidance laws with autopilot dynamics compensation.

This paper has proposed two continuous composite finite-time convergent guidance laws to intercept maneuvering targets in the presence of autopilot lag: one is for hit-to-kill and the other is for zeroing the line-of-sight (LOS) angular rate. More specifically, the nonlinear disturbance observer (NDOB) is used to estimate the lumped uncertainty online while the finite-time control technique is used to fulfill the design goal in finite time. The key feature in derivation of the proposed guidance law is that two integral-type Lyapunov functions are used to avoid analytic differentiation of virtual control law encountered with traditional backstepping. The finite-time stability of the closed-loop nonlinear observer-controller system is established using finite-time bounded (FTB) function and Lyapunov function methods. Numerical simulations with some comparisons are carried out to demonstrate the superiority of the proposed method.