Analysis of the relationship between MYCN gene and serum NSE and urinary VMA levels and neuroblastoma pathological features and prognosis.

The purpose of this study was to explore the relationship between the MYCN gene, serum neuron-specific enolase (NSE), urinary vanillylmandelic acid (VMA) levels, and neuroblastoma pathological features and prognosis. Ninety-four children with neuroblastoma treated in the hospital were selected to compare the differences in MYCN gene amplification, serum NSE, and urinary VMA levels in children with different clinicopathological features and prognoses. The proportion of children with MYCN gene copy number ≥10 in INSS stage 3-4 was higher than that of children with INSS stage 1-2 (P < 0.05); the proportion of children with MYCN gene copy number ≥10 in high-risk children in the COG risk stratification was higher than that of children with intermediate and low risk (P < 0.05); the serum NSE of children aged >12 months higher than that of children aged ≤12 months (P < 0.05); serum NSE of children with tumors >500 cm3 higher than that of children with tumors ≤500 cm3 (P < 0.05); serum NSE and urinary VMA of children with INSS staging of stages 3-4 were higher than that of children with stages 1 to 2 (P < 0.05); serum NSE and urinary VMA in children with lymph node metastasis were higher than that of children without lymph node metastasis (P < 0.05); serum NSE of children with MYCN gene copy number ≥10 was higher than that of children without lymph node metastasis (P < 0.05); the proportion of children with MYCN gene copy number ≥10 who died, and the percentages of serum NSE and urinary VMA were higher than those of the surviving children (P < 0.05). MYCN gene amplification and serum NSE and urinary VMA levels were related to the age, tumor size, INSS stage, COG stage, lymph node metastasis, and prognosis of the children with neuroblastoma.

Deep learning to assist composition classification and thyroid solid nodule diagnosis: a multicenter diagnostic study.

OBJECTIVES: This study aimed to propose a deep learning (DL)-based framework for identifying the composition of thyroid nodules and assessing their malignancy risk. METHODS: We conducted a retrospective multicenter study using ultrasound images from four hospitals. Convolutional neural network (CNN) models were constructed to classify ultrasound images of thyroid nodules into solid and non-solid, as well as benign and malignant. A total of 11,201 images of 6784 nodules were used for training, validation, and testing. The area under the receiver-operating characteristic curve (AUC) was employed as the primary evaluation index. RESULTS: The models had AUCs higher than 0.91 in the benign and malignant grading of solid thyroid nodules, with the Inception-ResNet AUC being the highest at 0.94. In the test set, the best algorithm for identifying benign and malignant thyroid nodules had a sensitivity of 0.88, and a specificity of 0.86. In the human vs. DL test set, the best algorithm had a sensitivity of 0.93, and a specificity of 0.86. The Inception-ResNet model performed better than the senior physicians (p < 0.001). The sensitivity and specificity of the optimal model based on the external test set were 0.90 and 0.75, respectively. CONCLUSIONS: This research demonstrates that CNNs can assist thyroid nodule diagnosis and reduce the rate of unnecessary fine-needle aspiration (FNA). CLINICAL RELEVANCE STATEMENT: High-resolution ultrasound has led to increased detection of thyroid nodules. This results in unnecessary fine-needle aspiration and anxiety for patients whose nodules are benign. Deep learning can solve these problems to some extent. KEY POINTS: • Thyroid solid nodules have a high probability of malignancy. • Our models can improve the differentiation between benign and malignant solid thyroid nodules. • The differential performance of one model was superior to that of senior radiologists. Applying this could reduce the rate of unnecessary fine-needle aspiration of solid thyroid nodules.

Neurogenic Monodermal Teratoma in the Scapula of a Child: A Case Report.

Background: Neurogenic monodermal teratomas (NMTs) have been reported in the ovaries but not from bone. Case Report: A 6-year-old girl had an incidentally discovered lesion in the right scapula. Upon removal, it was an NMT with predominant choroid plexus. The disease had not progressed for 31 months. Conclusion: Neurogenic monodermal teratomas can also occur in bone.

Leveraging deep learning to identify calcification and colloid in thyroid nodules.

Background: Both calcification and colloid in thyroid nodules are reflected as echogenic foci in ultrasound images. However, calcification and colloid have significantly different probabilities of malignancy. We explored the performance of a deep learning (DL) model in distinguishing the echogenic foci of thyroid nodules as calcification or colloid. Methods: We conducted a retrospective study using ultrasound image sets. The DL model was trained and tested on 30,388 images of 1127 nodules. All nodules were pathologically confirmed. The area under the receiver-operator characteristic curve (AUC) was employed as the primary evaluation index. Results: The YoloV5 (You Only Look Once Version 5) transfer learning model for thyroid nodules based on DL detection showed that the average sensitivity, specificity, and accuracy of distinguishing echogenic foci in the test 1 group (n = 192) was 78.41%, 91.36%, and 77.81%, respectively. The average sensitivity, specificity, and accuracy of the three radiologists were 51.14%, 82.58%, and 61.29%, respectively. The average sensitivity, specificity, and accuracy of distinguishing small echogenic foci in the test 2 group (n = 58) was 70.17%, 77.14%, and 73.33%, respectively. Correspondingly, the average sensitivity, specificity, and accuracy of the radiologists were 57.69%, 63.29%, and 59.38%. Conclusions: The study demonstrated that DL performed far better than radiologists in distinguishing echogenic foci of thyroid nodules as calcifications or colloid.

Prognostic analysis in children with focal cortical dysplasia II undergoing epilepsy surgery: Clinical and radiological factors.

Objective: The aim of this study was to investigate the value of clinical profiles and radiological findings in assessing postsurgical outcomes in children with focal cortical dysplasia (FCD) II while exploring prognostic predictors of this disease. Methods: We retrospectively reviewed 50 patients with postoperative pathologically confirmed FCD II from January 2016 to June 2021. The clinical profiles and preoperative radiological findings were measured and analyzed. The patients were classified into four classes based on the Engel Class Outcome System at the last follow-up. For the analysis, the patients were divided into two categories based on Engel I and Engel II-IV, namely, seizure-free and non-seizure-free groups. Qualitative and quantitative factors were subsequently compared by groups using comparative statistics. Receiver operating characteristic (ROC) curves were used to identify the predictors of prognosis in children with FCD II. Results: Thirty-seven patients (74%) had Engel class I outcomes. The minimum postsurgical follow-up was 1 year. At the epilepsy onset, patients who attained seizure freedom were older and less likely to have no apparent lesions on the preoperative MRI ("MRI-negative"). The non-seizure-free group exhibited a higher gray matter signal intensity ratio (GR) on 3D T1-MPRAGE images (p = 0.006), with a lower GR on T2WI images (p = 0.003) and FLAIR images (p = 0.032). The ROC curve indicated that the model that combined the GR value of all MRI sequences (AUC, 0.87; 95% CI, 0.77-0.97; p < 0.001; 86% sensitivity, 85% specificity) was able to predict prognosis accurately. Conclusion: A lower age at the onset or the MRI-negative finding of FCD lesions suggests a poor prognosis for children with FCD II. The model consisting of GR values from three MRI sequences facilitates the prognostic assessment of FCD II patients with subtle MRI abnormalities to prevent worse outcomes.

Nitric Oxide Acts as an Inhibitor of Postharvest Senescence in Horticultural Products.

Horticultural products display fast senescence after harvest at ambient temperatures, resulting in decreased quality and shorter shelf life. As a gaseous signal molecule, nitric oxide (NO) has an important physiological effect on plants. Specifically, in the area of NO and its regulation of postharvest senescence, tremendous progress has been made. This review summarizes NO synthesis; the effect of NO in alleviating postharvest senescence; the mechanism of NO-alleviated senescence; and its interactions with other signaling molecules, such as ethylene (ETH), abscisic acid (ABA), melatonin (MT), hydrogen sulfide (H2S), hydrogen gas (H2), hydrogen peroxide (H2O2), and calcium ions (Ca2+). The aim of this review is to provide theoretical references for the application of NO in postharvest senescence in horticultural products.

Novel Intronic Mutations Introduce Pseudoexons in DMD That Cause Muscular Dystrophy in Patients.

Background: Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are two subtypes of muscular dystrophy diseases caused by pathogenic mutations in the DMD gene. Until now, more than 4,600 disease-causing mutations in DMD have been reported. However, only 33 mutations were deep intronic, cases with this type of mutations were limited. Methods: In this study, we used a combination of complementary DNA (cDNA) and target DNA sequencing analysis in addition to conventional whole-exome sequencing (WES). Results: Three novel hemizygous mutations IVS11 + 17811C > G (c.1331 + 17811C > G), IVS21 + 3252A > G (c.2803 + 3252A > G) and IVS40 + 362A > G (c.5739 + 362A > G) were identified in DMD patients, while a reported hemizygous mutation IVS62-285A > G (c.9225-285A > G) was found in the BMD patient. These DMD mutations lead to pseudoexon insertions, causing the generation of truncated and dysfunctional dystrophin. Conclusion: This study defines three novel and one reported intronic mutations, which can result in DMD/BMD. We also emphasize the need to combine WES and cDNA-based methods to detect the variant in the very large DMD gene in which the mutational spectrum is complex.

Case Report: Myeloid Sarcoma Development During Treatment for B Cell Lymphoblastic Lymphoma in a Boy with KRAS/NRAS Gene Mutations.

Here, we report a rare case of a 12-year-old boy who was initially diagnosed with B cell lymphoblastic lymphoma (BLBL) and developed myeloid sarcoma (MS) eight months after chemotherapy. Next-generation sequencing (NGS) showed mutations of KRAS and NRAS genes in both the bone marrow and lymph node. He presented an abnormal karyotype of 46, XY, -9, der (16) t (9; 16) (q13; q12), +mar. He received chemotherapy according to the South China Children's Leukemia Group 2016 protocol. Complete remission was achieved by the 15th day post-treatment. Eight months later and immediately prior to the start of maintenance therapy, the patient developed fever, skin nodules in both upper arms, and enlargement of bilateral testes. Pathological analysis of skin and testicular biopsies suggested the diagnosis of myeloid sarcoma (MS). Again, NGS examination showed mutations of KRAS and NRAS genes. The patient underwent haploidentical hematopoietic stem cell transplantation but unfortunately did not survive. The interval of eight-month interval between the initial disease onset and MS brings into question whether MS developed as part of the initial onset of disease or as a secondary tumor in association with chemotherapy. Thus, understanding the pathogenesis of MS involving abnormalities of lymphoid progenitors may assist in the prediction of prognosis and development of novel target therapies.

miR-373 promotes neuroblastoma cell proliferation, migration, and invasion by targeting SRCIN1.

INTRODUCTION: Previous studies have shown that miR-373 functions as either a tumor suppressor or an oncogene depending on which type of cancer it's operating in. However, the functional role of miR-373 in neuroblastoma (NB) remains largely unclear. METHODS: Expression of miR-373 and SRC kinase signaling inhibitor 1 (SRCIN1) in 20 metastatic and 20 primary NB tissues was detected by quantitative real-time PCR (qRT-PCR) and Western blotting. MTT assay, flow cytometry analysis and transwell migration and invasion assays were performed to evaluate the influence of miR-373 inhibition on the growth, migration and invasion of NB cells, respectively. In vivo experiment was applied to determine the effect of miR-373 inhibition on tumor growth. Dual-luciferase reporter assay was used to confirm the interaction between miR-373 and SRCIN1. RESULTS: We observed a significant increase in the expression of miR-373 in metastatic NB samples compared with primary NB samples, and this was inversely correlated with SRCIN1 expression. Functional studies revealed that depletion of miR-373 inhibited in vitro NB cell growth, migration and invasion, and also suppressed tumor growth in an in vivo mouse model. Moreover, we identified that SRCIN1 was a direct and functional target gene of miR-373. Silencing of SRCIN1 partially rescued the antimiR-373-mediated inhibition of cell growth, migration and invasion. CONCLUSION: The data from our study verified a potential oncogenic role of miR-373 in NB cells that occurs through direct targeting SRCIN1. The newly identified miR-373/SRCIN1 axis represents a new potential candidate for therapeutic intervention of malignant NB.

A case of congenital rhabdomyosarcoma.

A 6-month-old girl presented with a congenital orbital tumor diagnosed as congenital embryonal rhabdomyosarcoma. Given the location, complete surgical resection was impossible. Management with chemotherapy and proton therapy resulted in complete clearance. This case highlights the clinical and histologic features of cutaneous congenital embryonal rhabdomyosarcoma.

Fibrosis, adipogenesis, and muscle atrophy in congenital muscular torticollis.

In the traditional view, muscle atrophy and interstitial fibrosis were regarded as the basic pathological features of congenital muscular torticollis (CMT). But in the ultrastructure study, the mesenchyme-like cells, myoblasts, myofibroblasts, and fibroblasts were found in the proliferation of interstitium of CMT. To investigate the characteristics of pathological features and the mechanisms of muscle atrophy in CMT, we retrospectively reviewed the medical records of 185 CMT patients from July 2009 to July 2011 in Shenzhen Children's Hospital in China and performed pathological studies. According to age, the 185 CMT patients were divided into 4 groups. All resected surgical specimens were processed for hematoxylin and eosin staining and Masson trichromic staining. Sudan III staining was used for frozen sections, whereas immunohistochemical staining for S-100, calpain-1, ubiquitin, and 20S proteasome was carried out on 40 CMT specimens. Eight adductor muscle specimens from 8 patients with development dysplasia of the hip were taken as control group in the immunohistochemical staining. By Masson trichromic staining, the differences in the percent area of fibrous tissue in each CMT groups were significant. In Sudan III staining and immunostaining for S-100, adipocyte hyperplasia was the pathological feature of CMT. Moreover, compared with controls, most atrophic muscle fibers in CMT specimens were found to show strong immunoreactivity for calpain-1, ubiquitin, and 20S proteasome. With increasing age, fibrosis peaked at both sides and it was low in middle age group. Adipocytes increased with age. The characteristics of pathological features in CMT are changeable with age. The calpain and the ubiquitin-proteasome system may play a role in muscle atrophy of CMT. In the CMT, adipogenesis, fibrogenesis, and myogenesis may be the results of mesenchyme-like cells in SCM (sternocleidomastoid muscle). In conclusion, the present study furthermore supports maldevelopment of the fetal SCM theory for etiology of CMT.

Primary central nervous system extranodal NK/T cell lymphoma, nasal type, with antecedent hemophagocytic syndrome in a child.

Primary central nervous system (CNS) extranodal natural killer (NK)/T-cell lymphoma, nasal type (NKTCL), is an exceedingly uncommon entity. Here, we present a case of CNS NKTCL that manifested initially as hemophagocytic syndrome 4 months earlier in a 13-year-old girl. Histological examination revealed the cerebellum mass was composed of large-sized and atypical tumor cells, with an angiocentric and angiodestructive growth pattern and prominent necrosis. The tumor cells exhibited marked pleomorphism with conspicuous nucleoli and prominent mitotic activity. Immunohistochemical staining showed the tumor cells were positive for CD45, CD2, CD3ε, CD30, CD43, CD56, and granzyme B. Epstein-Barr virus--encoded ribonucleic acid was expressed in almost all of the nuclei of the lymphoma cells. The T-cell receptor γ chain gene rearrangement study showed no evidence of a clonal rearrangement. The patient was treated with etoposide and dexamethasone and died a few days after the operation. As far as we know, this case is the 1st pediatric and female patient of primary CNS NKTCL with antecedent hemophagocytic syndrome, which highlights the clinical data and is helpful for the diagnosis of this tumor.

[ALK gene mutations in childhood neuroblastoma].

OBJECTIVE: To investigate mutations of anaplastic lymphoma kinase (ALK) in Chinese children with neuroblastoma (NB). METHODS: Genomic DNA was extracted from 22 cases of paraffin-embedding NB tumor tissues. Gene mutations in the exons 20-26 which were mutational hotspots of ALK were analyzed by PCR-DNA direct sequencing. RESULTS: A novel synonymous mutation C3586T (Leu1196Leu) and a known synonymous mutation C3375A (Gly1125Gly) were found and located at exon 23 and exon 21 of ALK respectively. There were 10 cases (46%) of known synonymous mutation C3375A in 22 cases of NB. The C3375A allelic frequency was 27%. No statistically significant correlation was found between mutation C3375A and clinical parameters of NB such as age, sex, metastasis and tumor differentiation. Mutation was not found in the other 5 exons. CONCLUSIONS: A novel ALK gene synonymous mutation C3586T was identified using PCR-DNA sequencing. A known mutation C3375A in ALK was successfully identified in children, and its incidence is not influenced by the clinical features of childhood NB.

[Study on the changes in endogenous oxidation agents and levels of anti-oxidation agents in patients with cerebral vascular disease].

OBJECTIVE: To investigate serum levels of endogenous oxidation agents, anti-oxidation agents and clinical significance in the patients with cerebral vascular disease (CVD). METHODS: Using biochemical methods, the levels of serum nitric oxide (NO), nitric oxide synthase (NOS), malondialdehyde (MDA) and anti-oxidants vitamin E (VitE), vitamin C (VitC), superoxide dismutase (SOD) in 49 patients with cerebral hemorrhage (CH), 65 patients with cerebral infarction(CI) and 35 patients with other nervous system diseases and 34 healthy controls were determined. RESULTS: In CH and CI groups, the levels of serum NO and MDA and the activity of serum NOS were significantly higher than that of the two other groups (P<0.05 or P<0.01). On the other hand, the patients with CH and CI had lower VitE, VitC levels and SOD activity than that of the two control groups (P<0.05 or P<0.01). CONCLUSION: These findings suggest NO and NOS plays an important role in pathogenesis of cerebral damage after CH and CI. Determination of the concentrations of NO, VitE, VitC, MDA level, and NOS and SOD activity in serum can also help judge the seriousness and the course of the disease.