Whole-tumoral metabolic heterogeneity in 18F-FDG PET/CT is a novel prognostic marker for neuroblastoma.

BACKGROUND: Neuroblastoma (NB) is a highly heterogeneous tumor, and more than half of newly diagnosed NB are associated with extensive metastases. Accurately characterizing the heterogeneity of whole-body tumor lesions remains clinical challenge. This study aims to quantify whole-tumoral metabolic heterogeneity (WMH) derived from whole-body tumor lesions, and investigate the prognostic value of WMH in NB. METHODS: We retrospectively enrolled 95 newly diagnosed pediatric NB patients in our department. Traditional semi-quantitative PET/CT parameters including the maximum standardized uptake value (SUVmax), the mean standardized uptake value (SUVmean), the peak standardized uptake value (SUVpeak), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured. These PET/CT parameters were expressed as PSUVmax, PSUVmean, PSUVpeak, PMTV, PTLG for primary tumor, WSUVmax, WSUVmean, WSUVpeak, WMTV, WTLG for whole-body tumor lesions. The metabolic heterogeneity was quantified using the areas under the curve of the cumulative SUV-volume histogram index (AUC-CSH index). Intra-tumoral metabolic heterogeneity (IMH) and WMH were extracted from primary tumor and whole-body tumor lesions, respectively. The outcome endpoints were overall survival (OS) and progression-free survival (PFS). Survival analysis was performed utilizing the univariate and multivariate Cox proportional hazards regression. The optimal cut-off values for metabolic parameters were obtained by receiver operating characteristic curve (ROC). RESULTS: During follow up, 27 (28.4%) patients died, 21 (22.1%) patients relapsed and 47 (49.5%) patients remained progression-free survival, with a median follow-up of 35.0 months. In survival analysis, WMTV and WTLG were independent indicators of PFS, and WMH was an independent risk factor of PFS and OS. However, IMH only showed association with PFS and OS. In addition to metabolic parameters, the International Neuroblastoma Staging System (INSS) was identified as an independent risk factor for PFS, and neuron-specific enolase (NSE) served as an independent predictor of OS. CONCLUSION: WMH was an independent risk factor for PFS and OS, suggesting its potential as a novel prognostic marker for newly diagnosed NB patients.

Risk factors, impact and treatment of postoperative lymphatic leakage in children with abdominal neuroblastoma operated on by laparotomy.

BACKGROUND: Lymphatic leakage is one of the postoperative complications of neuroblastoma. The purpose of this study is to summarize the clinical characteristics and risk factors of lymphatic leakage and try to find effective prevention and treatment measures. METHODS: A retrospective study included 186 children with abdominal neuroblastoma, including 32 children of lymphatic leakage and 154 children of non-lymphatic leakage. The clinical information, surgical data, postoperative abdominal drainage, treatment of lymphatic leakage and prognosis of the two groups were collected and analyzed. RESULTS: The incidence of lymphatic leakage in this cohort was 14% (32 children). Through univariate analysis of lymphatic leakage group and non-lymphatic leakage group, we found that lymphatic leakage increased the complications, prolonged the time of abdominal drainage and hospitalization, and delayed postoperative chemotherapy (p < 0.05). In this cohort, the median follow-up time was 46 (95% CI: 44-48) months. The follow-up data of 7 children were partially missing. 147 children survived, of which 23 had tumor recurrence (5 children recurred in the surgical area). 37 children died, of which 32 had tumor recurrence (9 children recurred in the operation area). In univariate analysis, there was no statistical difference in overall survival (p = 0.21) and event-free survival (p = 0.057) between lymphatic leakage group and non-lymphatic leakage group, while 3-year cumulative incidence of local progression was higher in lymphatic leakage group (p = 0.015). However, through multivariate analysis, we found that lymphatic leakage did not affect event-free survival, overall survival and cumulative incidence of local progression in children with neuroblastoma. Resection of 5 or more lymphatic regions was an independent risk factor for lymphatic leakage after neuroblastoma surgery. All 32 children with lymphatic leakage were cured by conservative treatment without surgery. Of these, 75% (24/32) children were cured by fat-free diet or observation, 25% (8/32) children were cured by total parenteral nutrition. The median drain output at diagnosis in total parenteral nutrition group was higher than that in non-total parenteral nutrition group (p < 0.001). The cut-off value was 17.2 ml/kg/day. CONCLUSIONS: Lymphatic leakage does not affect the prognosis of children with neuroblastoma, but long-term drain output caused by lymphatic leakage will still adversely affect postoperative complications and follow-up treatment, which requires attention and active treatment measures. More attention should be paid to the children with 5 or more lymphatic regions resection, and the injured lymphatic vessels should be actively found and ligated after tumor resection to reduce the postoperative lymphatic leakage. Early application of total parenteral nutrition is recommended for those who have drain output at diagnosis of greater than 17.2 ml/kg/day. LEVEL OF EVIDENCE: Level III, Treatment study (Retrospective comparative study).

Strain-Controlled Formation Energy and Migration of Nitrogen Vacancy in Al1-xScxN: A First-Principles Study.

The impact of strain on the formation energy and migration behavior of nitrogen vacancies (VNs) in Al1-xScxN has been investigated by first-principles calculations. The formation energy of VNs is obtained by total energy calculations. The migration barrier calculation utilizes the climbing nudged elastic band method. It is found that the formation energy of VNs is highly tunable with respect to the strain. The formation energy of VNs increases with the tensile strain increasing to +4% and decreases with the increasing compressive strain to -4%. A minimum formation energy of 4.11 eV is obtained when -4% strain is applied. Furthermore, the migration behavior of VNs is studied by calculating the migration barriers. Calculation results show that the migration barrier is strongly affected by strain. When the strain is -4%, the barrier is 2.46 eV while the barrier is increased to 2.71 eV under +4% strain. Therefore, a tensile strain can prevent the formation and migration of VNs. These findings suggest that strain engineering may serve as a tool for regulating VNs behavior in Al1-xScxN, potentially alleviating the ferroelectric degradations associated with VNs.

Exploring the stable structures of cerium oxide nanoclusters using high-dimensional neural network potential.

Cerium clusters have been extensively applied in industry owing to their extraordinary properties for oxygen storage and redox catalytic activities. However, their atomically precise structures have not been studied because of the lack of a reliable method to efficiently sample their complex structures. Herein, we combined a neural network algorithm with density functional theory calculations to establish a high-dimensional potential to search for the global minimums of cerium oxide clusters. Using Ce14O28 as well as its reduced state Ce14O27 and oxidized state Ce14O29 with ultra-small dimensions of ∼1.0 nm as examples, we found that these three clusters adopt pyramid-like structures with the lowest energies, which was obtained by exploring 100 000 configurations in large feasible spaces. Further the neural network potential-enhanced molecular dynamics calculations indicated that these cluster structures are stable at high temperature. The electronic structure analysis suggested that these clusters are highly active and easily lose oxygen. This work demonstrated that neural network potentials can be useful for exploring the stable structures of metal oxide nanoclusters in practical applications.

A Primary Report 166 Cases of Abdominal or Pelvic Neuroblastoma Surgery Utilizing the International Neuroblastoma Surgical Report Form (INSRF).

BACKGROUND AND AIMS: Surgery is pivotal in the management of neuroblastoma (NB), particularly in patients with Image-Defined Risk Factors (IDRFs). The International Neuroblastoma Surgical Report Form (INSRF) was introduced to enhance surgical reporting quality and analyze the defining role of extensive surgery in NB. This study reports our experience with INSRF and explores new criteria for evaluating the extent of surgical resection. METHODS: INSRF was deployed to critically analyze 166 patients with abdominal or pelvic NB who underwent surgery at our department between October 2021 and June 2023. Patient demographics, clinical characteristics, surgical datasets, and postoperative complications were described in detail. Receiver operating characteristic (ROC) curves were used to explore a new method to evaluate the extent of resection. A questionnaire was formulated to obtain attitudes/feedback and commentary from surgical oncologists with INSRF. RESULTS: 166 neuroblastoma patients with a median disease age 36.50 months. This study collated 320 INSRF reports. Among the 166 index cases, 137 were documented by two surgeons, with a concordance rate of 16.78%. Items with high inconsistency were (i) the extent of tumor resection (29.20%), (ii) renal vein involvement (25.55%), (iii) abdominal aorta encasement (16.79%), and (iv) mesenteric infiltration (17.52%). According to INSRF, the extent of resection was complete excision in 86 (51.81%) patients, minimal residual tumor < 5 cm3 in 67 (40.36%) patients, and incomplete excision > 5 cm3 in 13 (7.83%) patients. In ROC curve analysis, the number of vessels encased by tumors > 3 had a high predictive value in determining that a tumor could not be completely resected (AUC 0.916, sensitivity 0.838, specificity 0.826) using INSRF as the gold standard reference. The questionnaires showed that surgeons agreed that the extent of resection and tumor involvement of organ/vascular structures were important, while the definition and intervention(s) of intraoperative complications were less operational and understandable. CONCLUSIONS: INSRF has significant clinical application in neuroblastoma surgery. The extent of resection can be predicted based on the number of tumor-encased blood vessels. Supplementary information should be considered with the INSRF to aid practitioner reporting. Multicenter studies are needed to explore the defining role of INSRF in NB surgical management.

Renal preservation in high-risk retroperitoneal neuroblastoma: Impact on survival and local progression.

BACKGROUND: Retroperitoneal neuroblastomas predominantly encroach upon critical structures, complicating surgical intervention and yielding elevated rates of surgery-associated complications. The kidney and renal vasculature represent the organs most susceptible to retroperitoneal neuroblastoma infiltration. Prior investigations have revealed high nephrectomy incidence and a paucity of renal-preserving surgical approaches. METHODS: A retrospective analysis was undertaken, examining patients with retroperitoneal neuroblastoma who underwent surgical procedures from January 2018 to December 2019 at Beijing Children's Hospital. RESULTS: The study encompassed 225 patients, presenting a median age of 37 months. Concomitant nephrectomy and tumor excision were performed in 11 (4.9%) patients, while 214 (95.1%) patients successfully preserved their kidneys during surgery. Among the patients who retained their kidneys, 8 (3.5%) experienced renal atrophy postoperatively. Predominant rationales for simultaneous nephrectomy included tumor invasion into the renal hilum (n = 9), markedly diminished function of the affected kidney (n = 2), and ureteral infiltration (n = 1). Subsequent to a median follow-up duration of 43 months, the outcomes demonstrated no considerable divergence in overall survival (OS) and event-free survival (EFS) between the nephrectomy and renal-preserving cohorts among high-risk (HR) neuroblastoma patients. Among the eight HR children who underwent nephrectomy, four experienced local recurrence. The nephrectomy cohort exhibited a significantly elevated cumulative incidence of local progression (CILP) relative to the renal-preserving group. CONCLUSION: In high-risk retroperitoneal neuroblastoma patients, nephrectomy does not enhance CILP, EFS, or OS. The guiding surgical tenet involves preserving the kidney while striving for gross total resection of the primary neoplasm, barring instances of severe deterioration of the affected renal function.

Pediatric adrenocortical carcinoma: clinical features and application of neoadjuvant chemotherapy.

OBJECTIVE: To summarize the clinical characteristics of children with adrenocortical carcinoma (ACC) and preliminarily explore the indications for and efficacy of neoadjuvant chemotherapy in certain patients. METHODS: The data of 49 children with adrenocortical tumors (ACT) in the past 15 years were retrospectively analyzed, and after pathology assessment using Weiss system grading, 40 children diagnosed with ACC were included. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and three-dimensional (3D) reconstruction of contrast-enhanced computed tomography data were used to evaluate the response to neoadjuvant chemotherapy. RESULTS: Forty patients (17 males, 23 females) with ACC were enrolled. Abnormal hormone levels were common in children with ACC (n = 31), and in terms of clinical presentation, sexual precocity was the most common (n = 14, 35.0%), followed by Cushing's syndrome (n = 12, 30.0%). Seven of 40 children received neoadjuvant chemotherapy due to a maximum lesion diameter greater than 10 cm (n = 4), invasion of surrounding tissues (n = 2), intravenous tumor thrombus (n = 2), and/or distant metastasis (n = 2); 2 patients achieved partial response, and 5 had stable disease according to the RECIST 1.1 standard. Furthermore, 3D tumor volume reconstruction was performed in 5 children before and after neoadjuvant chemotherapy. Tumor volumes were significantly reduced in all 5 children, with a median volume reduction of 270 (interquartile range, IQR 83, 293) (range: 49-413) ml. After surgery with/without chemotherapy, the 5-year overall survival rate for all children was 90.0% (95% CI-confidence interval 80.0-100.0%), and the 5-year event-free survival rate was 81.5% (95% CI 68.0-97.7%). CONCLUSION: In the diagnosis and treatment of pediatric ACC, a comprehensive endocrine evaluation is necessary to facilitate early diagnosis. Surgery and chemotherapy are important components of ACC treatment, and neoadjuvant chemotherapy should be considered for children with ACC who meet certain criteria, such as a large tumor, distant metastases, or poor general condition.

Evaluating the clinical efficacy and limitations of indocyanine green fluorescence-guided surgery in childhood hepatoblastoma: A retrospective study.

BACKGROUND: Indocyanine green (ICG) fluorescence guided surgery has been used to treat childhood hepatoblastoma (HB), but the advantages and disadvantages of this technique have not been fully discussed. The purpose of this study is to summarize the experience and to explore the clinical value of this technique for children with HB. METHODS: 45 children with HB who underwent ICG fluorescence guided surgery (n = 22) and general surgery (n = 23) in our center from January 2020 to December 2022 were enrolled retrospectively. RESULTS: All the liver tumors in the ICG group showed hyperfluorescence, including total and partial fluorescent types. With the help of ICG navigation, minimally invasive surgery was performed in 3 cases. 18.2 % of cases with tumors could not be accurately identified under white light, but could be identified by fluorescence imaging. The fluorescent cutting lines of 59.1 % of cases were consistent with the safe cutting lines. In 36.4 % of cases, the fluorescence boundary was not clear because of tumor necrosis. In 36.4 % of cases, the fluorescence could not be detected on the inner edge of the tumors because of the depth. A total of 29 ICG (+) suspicious lesions were found during the operations, of which 5 were true positive lesions. CONCLUSION: ICG fluorescence guided surgery is safe and feasible in children with HB. This technique is helpful for locating tumors, determining margin and finding small lesions with negative imaging, especially in minimally invasive surgery. However, preoperative chemotherapy, tumor necrosis, tumor depth, and ICG administration impact the effect of fluorescence imaging.

Integration of clinical characteristics and molecular signatures of the tumor microenvironment to predict the prognosis of neuroblastoma.

This study aimed to analyze the clinical characteristics, cell types, and molecular characteristics of the tumor microenvironment to better predict the prognosis of neuroblastoma (NB). The gene expression data and corresponding clinical information of 498 NB patients were obtained from the Gene Expression Omnibus (GEO: GSE62564) and ArrayExpress (accession: E-MTAB-8248). The relative cell abundances were estimated using single-sample gene set enrichment analysis (ssGSEA) with the R gene set variation analysis (GSVA) package. We performed Cox regression analyses to identify marker genes indicating cell subsets and combined these with prognostically relevant clinical factors to develop a new prognostic model. Data from the E-MTAB-8248 cohort verified the predictive accuracy of the prognostic model. Single-cell RNA-seq data were analyzed by using the R Seurat package. Multivariate survival analysis for each gene, using clinical characteristics as cofactors, identified 34 prognostic genes that showed a significant correlation with both event-free survival (EFS) and overall survival (OS) (log-rank test, P value < 0.05). The pathway enrichment analysis revealed that these prognostic genes were highly enriched in the marker genes of NB cells with mesenchymal features and protein translation. Ultimately, USP39, RPL8, IL1RAPL1, MAST4, CSRP2, ATP5E, International Neuroblastoma Staging System (INSS) stage, age, and MYCN status were selected to build an optimized Cox model for NB risk stratification. These samples were divided into two groups using the median of the risk score as a cutoff. The prognosis of samples in the poor prognosis group (PP) was significantly worse than that of samples in the good prognosis group (GP) (log-rank test, P value < 0.0001, median EFS: 640.5 vs. 2247 days, median OS: 1279.5 vs. 2519 days). The risk model was also regarded as a prognostic indicator independent of MYCN status, age, and stage. Finally, through scRNA-seq data, we found that as an important prognostic marker, USP39 might participate in the regulation of RNA splicing in NB. Our study established a multivariate Cox model based on gene signatures and clinical characteristics to better predict the prognosis of NB and revealed that mesenchymal signature genes of NB cells, especially USP39, were more abundant in patients with a poor prognosis than in those with a good prognosis. KEY MESSAGES: Our study established a multivariate Cox model based on gene signatures and clinical characteristics to better predict the prognosis of NB and revealed that mesenchymal signature genes of NB cells, especially USP39, were more abundant in patients with a poor prognosis than in those with a good prognosis. USP39, RPL8, IL1RAPL1, MAST4, CSRP2, ATP5E, International Neuroblastoma Staging System (INSS) stage, age, and MYCN status were selected to build an optimized Cox model for NB risk stratification. These samples were divided into two groups using the median of the risk score as a cutoff. The prognosis of samples in the poor prognosis group (PP) was significantly worse than that of samples in the good prognosis group (GP). Finally, through scRNA-seq data, we found that as an important prognostic marker, USP39 might participate in the regulation of RNA splicing in NB.

{[In2S7]8-}∞ Chain and Isolated HgS4 Planar Unit Constructed One-Dimensional Pentanary Sulfide K2Ba7HgIn4S16 Exhibiting Nonlinear-Optical Activity.

Hg-based chalcogenides possess diverse structures, large nonlinear-optical (NLO) responses, and suitable birefringences, making them potentially suitable for numerous crucial criteria of practical application as infrared (IR) NLO crystals. Here, a new pentanary Hg-based sulfide K2Ba7HgIn4S16 has been discovered by a high-temperature solid-state method. It crystallizes in the orthorhombic P21212 space group, and its one-dimensional structure is constructed by {[In2S7]8-}∞ chains and isolated [HgS4]6- planar quadrilateral units located bewteeen the chains, representing a novel type of chalcogenide. K2Ba7HgIn4S16 exhibits a moderate NLO effect of 0.5 × AGS at 2.1 µm and a high laser-induced damage threshold of ∼5.8 × AGS, as well as a band gap of 2.98 eV, demonstrating that K2Ba7HgIn4S16 is a potential IR NLO material. This work enriches the structural chemistry of chalcogenides and the family of Hg-based IR NLO chalcogenides.

Safety and feasibility of laparoscopic resection of abdominal neuroblastoma without image-defined risk factors: a single-center experience.

OBJECTIVE: To explore the criteria, safety and efficacy of laparoscopic surgery in pediatric neuroblastoma (NB). METHODS: A retrospective study of 87 patients with NB without image-defined risk factors (IDRFs) between December 2016 and January 2021 at Beijing Children's Hospital was conducted. Patients were divided into two groups according to the surgical procedure. RESULTS: Between the 87 patients, there were 54 (62.07%) cases in the open surgery group and 33 (37.93%) cases in the laparoscopic surgery group. There were no significant differences between the two groups regarding demographic characteristics, genomic and biological features, operating time or postoperative complications. However, in terms of intraoperative bleeding (p = 0.013) and the time to start postoperative feeding after surgery (p = 0.002), the laparoscopic group was obviously better than the open group. Furthermore, there was no significant difference in the prognosis between the two groups, and no recurrence or death was observed. CONCLUSION: For children with localized NB who have no IDRFs, laparoscopic surgery could be performed safely and effectively. Surgeons who are skilled in this can help children reduce surgical injuries, speed up postoperative recovery, and obtain the same prognosis as open surgery.

Clinical risk factors for patients with ruptured hepatoblastoma in children: a retrospective study from a single center in China.

OBJECTIVE: Hepatoblastoma (HB) tumor rupture is a high-risk criterion in the International Childhood Liver Tumors Strategy Group (SIOPEL) 3/4 protocol. However, the causes and risk factors for HB rupture are still unknown, and whether tumor rupture is an independent risk factor for HB prognosis is still controversial. The purpose of this study was to retrospectively analyze the clinical characteristics of children with HB tumor rupture and to search for clinical risk factors to conduct early prediction and intervention. METHODS: We conducted a retrospective study of 27 patients with HB rupture between July 2009 and July 2019. To further identify the risk factors for HB rupture, we included 97 nonruptured HB patients from January 2013 to January 2019. We searched for potentially useful characteristics for HB rupture by univariate and multivariate logistic regression analyses. RESULTS: There were 27 patients with HB rupture, with the median age of 31 (12, 69) months. Nineteen cases (70.37%) were spontaneous tumor rupture, 1 case (3.70%) was posttraumatic rupture, 2 cases (7.41%) were tumor rupture after the biopsy, and 5 cases (18.52%) were tumor rupture after chemotherapy. After the tumor rupture, 4 patients died of hemorrhagic shock and multiple organ dysfunction syndrome (MODS), 4 patients refused further therapy and were discharged against medical advice, and the remaining 19 patients were stable after emergency treatment. After the treatment, 14 patients survived without disease, 2 patients died, and 3 patients were lost to follow-up. The median follow-up was 48 (33, 60) months, the 3-year overall survival (OS) was 54.7%. Compared with the non-tumor rupture group by multivariate logistic regression analysis, it was found that the maximum diameter of the primary tumor > 13.4 cm, and vascular invasion were independent risk factors for tumor rupture. CONCLUSION: HB rupture is rare, but it seriously threatens the life and health of children. In the acute phase of tumor rupture, surgery, rescue chemotherapy, transcatheter arterial embolization (TAE) and other supportive care can be adopted. Large tumors and vascular invasion are risk factors for HB rupture. LEVEL OF EVIDENCE: Level IV.

Design and 3D FEM Analysis of a Flexible Piezoelectric Micromechanical Ultrasonic Transducer Based on Sc-Doped AlN Film.

In this paper, a flexible piezoelectric micromachined ultrasonic transducer (PMUT) based on Scandium (Sc)-doped Aluminum Nitride (AlN) film was designed and modeled by the three-dimensional finite element method (3D-FEM). The resonant frequency of 218.1 kHz was reported. It was noticeable that a high effective electromechanical coupling coefficient (k2eff) of 1.45% was obtained when a combination of a flexible PI and a thin Si layer was used as the PMUT supporting structure layer. Compared with a pure Si supporting layer counterpart, the coupling coefficient had been improved by 110.68%. Additionally, the increase of Sc doping concentration in AlN film further enhanced the device electromechanical coupling coefficient and resulted in an improvement for transmitting/receiving sensitivity of the proposed flexible PMUT. When the doping concentration of Sc reached 30%, the emission sensitivity was as large as 1.721 µm/V, which was 2.86 times greater than that of conventional AlN film-based PMUT. The receiving sensitivity was found to be 2.11 V/KPa, which was as high as 1.23 times the performance of an undoped device. Furthermore, the bending simulation result showed that the proposed flexible PMUT device can maintain a good mechanical stability when the bending radius is greater than 1.5 mm. The simulation of sound field characteristics demonstrated that the flexible PMUT based on AlScN could receive stable sound pressure signals under the bending radius of 1.5 cm.

Sciatic nerve block downregulates the BDNF pathway to alleviate the neonatal incision-induced exaggeration of incisional pain via decreasing microglial activation.

Sciatic nerve block is under investigation as a possible therapeutic strategy for neonatal injury-induced exaggeration of pain responses to reinjury. Spinal microglial priming, brain-derived neurotrophic factor (BDNF) and Src homology-2 domain-containing protein tyrosine phosphatase-2 (SHP2) participate in exaggerated incisional pain induced by neonatal incision. However, effects of sciatic nerve block on exacerbated incisional pain and underlying mechanisms remain unclear. Here, we demonstrated that sciatic nerve block alleviates pain hypersensitivity and microglial activation in rats subjected to neonatal incision and adult incision (nIN-IN). Chemogenetic activation or inhibition of spinal microglia attenuates or mimics effects of sciatic nerve block on pain hypersensitivity, respectively. Moreover, α-amino-3-hydroxy- 5-methy- 4-isoxazole propionate (AMPA) receptor subunit GluA1 contributes to the exaggeration of incisional pain. The inhibition of BDNF or SHP2 blocks upregulations of downstream molecules in nIN-IN rats. Knockdown of SHP2 attenuates the increase of GluA1 induced by injection of BDNF in adult rats with only neonatal incision. The inhibition of microglia or ablation of microglial BDNF attenuates upregulations of SHP2 and GluA1. Additionally, sciatic nerve block downregulates the expression of these three molecules. Upregulation of BDNF, SHP2 or AMPA receptor attenuates sciatic nerve block-induced reductions of downstream molecules and pain hypersensitivity. Microglial activation abrogates reductions of these three molecules induced by sciatic nerve block. These results suggest that decreased activation of spinal microglia contributes to beneficial effects of sciatic nerve block on the neonatal incision-induced exaggeration of incisional pain via downregulating BDNF/SHP2/GluA1-containing AMPA receptor signaling. Thus, sciatic nerve block may be a promising therapy.

Clinical parameters combined with radiomics features of PET/CT can predict recurrence in patients with high-risk pediatric neuroblastoma.

BACKGROUND: This retrospective study aimed to develop and validate a combined model based [18F]FDG PET/CT radiomics and clinical parameters for predicting recurrence in high-risk pediatric neuroblastoma patients. METHODS: Eighty-four high-risk neuroblastoma patients were retrospectively enrolled and divided into training and test sets according to the ratio of 3:2. [18F]FDG PET/CT images of the tumor were segmented by 3D Slicer software and the radiomics features were extracted. The effective features were selected by the least absolute shrinkage and selection operator to construct the radiomics score (Rad_score). And the radiomics model (R_model) was constructed based on Rad_score for prediction of recurrence. Then, univariate and multivariate analyses were used to screen out the independent clinical risk parameters and construct the clinical model (C_model). A combined model (RC_model) was developed based on the Rad_score and independent clinical risk parameters and presented as radiomics nomogram. The performance of the above three models was assessed by the area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA). RESULTS: Seven radiomics features were selected for building the R_model. The AUCs of the C_model in training and test sets were 0.744 (95% confidence interval [CI], 0.595-0.874) and 0.750 (95% CI, 0.577-0.904), respectively. The R_model yielded AUCs of 0.813 (95% CI, 0.685-0.916) and 0.869 (95% CI, 0.715-0.985) in the training and test sets, respectively. The RC_model demonstrated the largest AUCs of 0.889 (95% CI, 0.794-0.963) and 0.892 (95% CI, 0.758-0.992) in the training and test sets, respectively. DCA demonstrated that RC_model added more net benefits than either the C_model or the R_model for predicting recurrence in high-risk pediatric neuroblastoma. CONCLUSIONS: The combined model performed well for predicting recurrence in high-risk pediatric neuroblastoma, which can facilitate disease follow-up and management in clinical practice.

Prediction for Mitosis-Karyorrhexis Index Status of Pediatric Neuroblastoma via Machine Learning Based 18F-FDG PET/CT Radiomics.

Accurate differentiation of intermediate/high mitosis-karyorrhexis index (MKI) from low MKI is vital for the further management of neuroblastoma. The purpose of this research was to investigate the efficacy of 18F-FDG PET/CT-based radiomics features for the prediction of MKI status of pediatric neuroblastoma via machine learning. A total of 102 pediatric neuroblastoma patients were retrospectively enrolled and divided into training (68 patients) and validation sets (34 patients) in a 2:1 ratio. Clinical characteristics and radiomics features were extracted by XGBoost algorithm and were used to establish radiomics and clinical models for MKI status prediction. A combined model was developed, encompassing clinical characteristics and radiomics features and presented as a radiomics nomogram. The predictive performance of the models was evaluated by AUC and decision curve analysis. The radiomics model yielded AUC of 0.982 (95% CI: 0.916, 0.999) and 0.955 (95% CI: 0.823, 0.997) in the training and validation sets, respectively. The clinical model yielded AUC of 0.746 and 0.670 in the training and validation sets, respectively. The combined model demonstrated AUC of 0.988 (95% CI: 0.924, 1.000) and 0.951 (95% CI: 0.818, 0.996) in the training and validation sets, respectively. The radiomics features could non-invasively predict MKI status of pediatric neuroblastoma with high accuracy.

Congenital Bilateral Wilms Tumor: A Case Report.

Compare to congenital mesoblastic nephroma in fetus, congenital wilms tumor is extremely rare. Herein we report a case of congenital bilateral solid masses on antenatal ultrasound. The mass was evaluated by ultrasonography and contrast computed tomography scan in postnatal period, and the patient was undergoing tumor enucleation separately in short period after neoadjuvant chemotherapy. The diagnosis was confirmed by histology analysis for each side, and the treatment was taken according to the International Society of Pediatric Oncology.

Current status in the discovery of dual BET/HDAC inhibitors.

The development of desired multitarget agents may provide an attractive and cost-effective complement or alternative to drug combinations. Bromodomain and extraterminal domain (BET) and histone deacetylase (HDAC), as important epigenetic modulators, are attractive targets in drug discovery and development. Considering the fact that BET and HDAC inhibitors exert a synergistic effect on cellular processes in cancer cells, the design of dual BET/HDAC inhibitors may be a rational strategy to improve the efficacy of their single-target drugs for tumor treatment. In the current review, we depict the development of dual BET/HDAC inhibitors and particularly highlight their structure-activity relationships (SARs), binding modes, and biological functions with the aim to facilitate rational drug design and develop more dual BET/HDAC inhibitors.

A Novel Homozygous TTC7A Missense Mutation Results in Familial Multiple Intestinal Atresia and Combined Immunodeficiency.

Rare autosomal-recessive variants in tetratricopeptide repeat domain 7A (TTC7A) gene have been shown to cause intestinal and immune disorders of variable severity. Missense mutations in TTC7A gene, usually retaining most of the functional motifs, is associated with relative milder clinical presentations. In this study, we reported a patient who was suffering from severe multiple intestinal atresia (MIA) with combined immunodeficiency (CID) that led to the pyloric diaphragm, ileum atresia, colon stenosis, and multiple episodes of sepsis. In spite of several surgeries and supportive treatment, the patient died of severe sepsis and multiple organ failure at age of 3 months. The whole exome sequencing (WES) of peripheral blood samples identified a novel homozygous TTC7A missense mutation (c. 206T>C, p. L69P), inherited from his parents with consanguineous marriage. In silico analysis revealed that a hydrogen bond present between Gly65 and Leu69 in the wild-type TTC7A was disrupted by the Leu69Pro mutation. Moreover, this homozygous missense mutation led to a reduced TTC7A expression in lymphocytes and intestinal tissues, accompanied by impeded lymphocyte development. Further studies demonstrated that the PI4K-FAM126A-EFR3A pathway was impaired in colon tissues. Our data strongly support the linkage of severe MIA-CID with the missense mutation in TTC7A gene. More knowledge of the TTC7A protein functions will have important therapeutic implications for patients with MIA-CID.