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In this study, we designed a self-focused ultrasonic transducer made of polyvinylidene fluoride (PVDF). This transducer involves a back-reflector, which is modeled after tapetum lucidum in the eyes of some nocturnal animals. The bionic structure reflects the ultrasound, which passes through the PVDF membrane, back to PVDF and provides a second chance for the PVDF to convert the ultrasound to electric signals. This design increases the amount of ultrasound absorbed by the PVDF, thereby improving the detection sensitivity. Both ultrasonic and photoacoustic (PA) experiments were conduct to characterize the performance of the transducer. The results show that the fabricated transducer has a center frequency of 13.07â MHz, and a bandwidth of 96% at -6â dB. With an acoustic numerical aperture (NA) of 0.64, the transducer provides a lateral resolution of 140µm. Importantly, the bionic design improves the detection sensitivity of the transducer about 30%. Finally, we apply the fabricated transducer to optical-resolution (OR) and acoustic-resolution photoacoustic microscopy (AR-PAM) to achieve multiscale-resolution PA imaging. Imaging of the bamboo leaf and the leaf skeleton demonstrates that the proposed transducer can provide high spatial resolution, better imaging intensity and contrast. Therefore, the proposed transducer design will be useful to enhance the performance of multiscale-resolution PAM.
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Tumor Rabdoide , Teratoma , Masculino , Humanos , Criança , Proteína SMARCB1 , Fatores de Transcrição , Tumor Rabdoide/patologia , Teratoma/patologiaAssuntos
Proteína Proto-Oncogênica N-Myc , Neuroblastoma , Proteínas Nucleares , Proteínas Oncogênicas , Humanos , Proteína Proto-Oncogênica N-Myc/genética , Neuroblastoma/genética , Neuroblastoma/patologia , Neuroblastoma/diagnóstico , Proteínas Oncogênicas/genética , Proteínas Oncogênicas/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Prognóstico , Amplificação de Genes , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismoRESUMO
MOTIVATION: Pediatric kidney disease is a widespread, progressive condition that severely impacts growth and development of children. Chronic kidney disease is often more insidious in children than in adults, usually requiring a renal biopsy for diagnosis. Biopsy evaluation requires copious examination by trained pathologists, which can be tedious and prone to human error. In this study, we propose an artificial intelligence (AI) method to assist pathologists in accurate segmentation and classification of pediatric kidney structures, named as AI-based Pediatric Kidney Diagnosis (APKD). RESULTS: We collected 2935 pediatric patients diagnosed with kidney disease for the development of APKD. The dataset comprised 93 932 histological structures annotated manually by three skilled nephropathologists. APKD scored an average accuracy of 94% for each kidney structure category, including 99% in the glomerulus. We found strong correlation between the model and manual detection in detected glomeruli (Spearman correlation coefficient r = 0.98, P < .001; intraclass correlation coefficient ICC = 0.98, 95% CI = 0.96-0.98). Compared to manual detection, APKD was approximately 5.5 times faster in segmenting glomeruli. Finally, we show how the pathological features extracted by APKD can identify focal abnormalities of the glomerular capillary wall to aid in the early diagnosis of pediatric kidney disease. AVAILABILITY AND IMPLEMENTATION: https://github.com/ChunyueFeng/Kidney-DataSet.
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Inteligência Artificial , Insuficiência Renal Crônica , Adulto , Humanos , Criança , Rim/diagnóstico por imagem , Rim/patologia , Insuficiência Renal Crônica/patologiaRESUMO
BACKGROUND: Steroid-resistant nephrotic syndrome (SRNS) is characterized by unrelieved proteinuria after an initial 4-8 weeks of glucocorticoid therapy. Genes in podocytes play an important role in causing SRNS. OBJECTIVE: This study aimed to report a pathogenic mutation in SRNS patients and investigate its effects on podocytes, as well as the pathogenic mechanism. METHODS: We screened out a novel mutation by using whole-exon sequencing in the SRNS cohort and verified it via Sanger sequencing. Conservative analysis and bioinformatic analysis were used to predict the pathogenicity of the mutation. In vitro, stable podocyte cell lines were constructed to detect the effect of the mutation on the function of the podocyte. Moreover, an in vivo mouse model of podocyte ANLN gene knockout (ANLNpodKO) was used to confirm clinical manifestations. Transcriptome analysis was performed to identify differential gene expression and related signaling pathways. RESULTS: ANLN E841K was screened from three unrelated families. ANLN E841K occurred in the functional domain and was predicted to be harmful. The pathological type of A-II-1 renal biopsy was minimal change disease, and the expression of ANLN was decreased. Cells in the mutation group showed disordered cytoskeleton, faster cell migration, decreased adhesion, increased endocytosis, slower proliferation, increased apoptosis, and weakened interaction with CD2 association protein. ANLNpodKO mice exhibited more obvious proteinuria, more severe mesangial proliferation, glomerular atrophy, foot process fusion, and increased tissue apoptosis levels than ANLNflox/flox mice after tail vein injection of adriamycin. Upregulated differentially expressed genes in cells of the mutation group were mainly enriched in the PI3K-AKT pathway. CONCLUSION: The novel mutation known as ANLN E841K affected the function of the ANLN protein by activating the PI3K/AKT/mTOR/apoptosis pathway, thus resulting in structural and functional changes in podocytes. Our study indicated that ANLN played a vital role in maintaining the normal function of podocytes. Video Abstract.
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Proteínas dos Microfilamentos , Síndrome Nefrótica , Podócitos , Animais , Humanos , Camundongos , Mutação/genética , Síndrome Nefrótica/genética , Síndrome Nefrótica/tratamento farmacológico , Síndrome Nefrótica/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Podócitos/patologia , Proteinúria , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas dos Microfilamentos/genéticaRESUMO
BACKGROUND: Plant respiratory burst oxidase homolog (Rboh) gene family produces reactive oxygen species (ROS), and it plays key roles in plant-microbe interaction. Most Rboh gene family-related studies mainly focused on dicotyledonous plants; however, little is known about the roles of Rboh genes in gramineae. RESULTS: A total of 106 Rboh genes were identified in seven gramineae species, including Zea mays, Sorghum bicolor, Brachypodium distachyon, Oryza sativa, Setaria italica, Hordeum vulgare, and Triticum aestivum. The Rboh protein sequences showed high similarities, suggesting that they may have conserved functions across different species. Duplication mode analysis detected whole-genome/segmental duplication (WGD)/(SD) and dispersed in the seven species. Interestingly, two local duplication (LD, including tandem and proximal duplication) modes were found in Z. mays, S. italica and H. vulgare, while four LD were detected in T. aestivum, indicating that these genes may have similar functions. Collinearity analysis indicated that Rboh genes are at a stable evolution state in all the seven species. Besides, Rboh genes from Z. mays were closely related to those from S. bicolor, consistent with the current understanding of plant evolutionary history. Phylogenetic analysis showed that the genes in the subgroups I and II may participate in plant-AM fungus symbiosis. Cis-element analysis showed that different numbers of elements are related to fungal induction in the promoter region. Expression profiles of Rboh genes in Z. mays suggested that Rboh genes had distinct spatial expression patterns. By inoculation with AM fungi, our transcriptome analysis showed that the expression of Rboh genes varies upon AM fungal inoculation. In particularly, ZmRbohF was significantly upregulated after inoculation with AM fungi. pZmRbohF::GUS expression analyses indicated that ZmRbohF was induced by arbuscular mycorrhizal fungi in maize. By comparing WT and ZmRbohF mutant, we found ZmRbohF had limited impact on the establishment of maize-AM fungi symbiosis, but play critical roles in regulating the proper development of arbuscules. CONCLUSIONS: This study provides a comprehensive analysis of the evolution relationship of Rboh genes in seven gramineae species. Results showed that several Rboh genes regulate maize-AM fungal symbiosis process. This study provides valuable information for further studies of Rboh genes in gramineae.
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Micorrizas , Micorrizas/fisiologia , Zea mays/metabolismo , Filogenia , Simbiose , Raízes de Plantas/genética , Regulação da Expressão Gênica de PlantasRESUMO
A coordinated increase in the photosynthetic rate (A) and photosynthetic nitrogen use efficiency (PNUE) is an effective strategy for improving crop yield and nitrogen (N) utilization efficiency. PNUE tends to decrease with increasing N levels, but there are natural variations. Consequently, leaf functional N partitioning in Brassica napus genotypes under different N rates was measured to explore the optimized N allocation model for synchronously increasing A and PNUE values. The results showed that genotypes whose PNUE increased with increasing N supply (PNUE-I) produced an approximate A value with a relatively low leaf N content, owing to reduced storage N (Nstore ) and close photosynthetic N (Npsn ) content. Partial least squares path modeling showed that A was dominated by the Npsn content, and PNUE was directly influenced by A and Nstore . The A value increased with the Npsn content until the Npsn content exceeded the threshold value. The boundary line of PNUE varied with the Npsn and Nstore proportions, indicating that the optimum Npsn and Nstore proportions were 51.6% and 40.3%, respectively. The Nstore proportion of PNUE-I was closer to the thresholds and benefited from lower increments in Rubisco content and nonprotein form storage N content with improved N supply. Optimized Nstore and Npsn trade-off by regulating increments in Nstore content with increased N supply, thereby promoting coordinated increases in A and PNUE.
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Brassica napus , Nitrogênio , Fotossíntese/fisiologia , Folhas de Planta/metabolismo , Ribulose-Bifosfato Carboxilase/metabolismo , Brassica napus/metabolismoRESUMO
Neuroblastoma is a heterogeneous paediatric malignant tumour. Telomere maintenance mechanism (TMM) by telomerase activation or alternative lengthening of telomeres (ALT) is a hallmark of high-risk neuroblastoma. However, the prior assays for telomerase, such as TERT expression by RNA sequencing or microarrays, may not be easy to perform in many histopathology laboratories in hospitals. The aims of this study are to assess the utility of ultrasensitive single-cell RNA in situ hybridisation (RNAscope), immunohistochemistry, and RT-qPCR on formalin-fixed, paraffin-embedded tumour samples as diagnostic tools for detecting TERT expression in neuroblastoma. In this study, we detected MYCN amplification in 22 of 222 cases (10%), TERT rearrangements in 18 of 220 cases (8%), and ALT activation in 39 of 222 cases (18%) using fluorescence in situ hybridisation (FISH). By RNA in situ hybridisation, 36 of 210 (17%) pretreatment neuroblastomas were found to have TERT overexpression, which was significantly associated with the high-risk group (33/78, 42%), TERT rearrangements (16/18, 89%), and MYCN amplification (13/22, 59%). None of the tumours with ALT showed TERT staining. In our study, 19 of the 55 MYCN non-amplified high-risk neuroblastomas displayed TERT mRNA expression, including 13 of the 14 TERT rearrangements, none of the 30 ALT-positive cases, and a significant proportion (6/11, 55%) that did not have the aforementioned genomic anomalies. RT-qPCR results correlated well with RNAscope levels (Spearman's rho=0.621, p<0.001, n=94). In conclusion, TERT RNA in situ hybridisation and RT-qPCR are suitable methods to evaluate TERT expression in neuroblastoma. The combination of detection of the genomic alterations and TERT mRNA expression is a powerful strategy for TMM activation detection, which can categorise neuroblastomas into multiple clinical subgroups for risk stratification in routine histopathology practice.
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Neuroblastoma , Telomerase , Criança , Humanos , Telomerase/genética , Telomerase/metabolismo , Proteína Proto-Oncogênica N-Myc/genética , Proteína Proto-Oncogênica N-Myc/metabolismo , Inclusão em Parafina , Neuroblastoma/diagnóstico , Neuroblastoma/genética , Neuroblastoma/patologia , Reação em Cadeia da Polimerase , RNA , RNA MensageiroRESUMO
Microcirculation imaging has significantly clinical value in early diagnosis and curative effect judgment of various diseases. The most superficial layer of the nailbed is rich in capillaries, which is suitable as a window on the microcirculation. However, few techniques can noninvasively observe the blood supply distribution of the nailbed, especially for high-resolution imaging of capillaries. In this study, we adapted an optical-resolution photoacoustic microscopy (OR-PAM) to image the nailbed microvasculature. The imaging sensitivity was significantly improved by hydration pretreatment of the nail. In vitro phantom experiments demonstrate that the sensitivity was improved about 3.5 times after hydration. In vivo imaging experiments of the nailbed microvasculature were conducted to further examine the enhanced sensitivity and practicability of OR-PAM. Moreover, the quantitative analysis of capillary loops showed that OR-PAM can extract the detection indicators including vascular morphology, diameter, and length, which provides a basis for clinical microcirculation detection using OR-PAM.
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Microscopia , Técnicas Fotoacústicas , Humanos , Microvasos/diagnóstico por imagem , Capilares , Análise Espectral , Microcirculação , Técnicas Fotoacústicas/métodosRESUMO
BACKGROUND: MYCN gene amplification is a powerful indicator of poor prognosis of neuroblastoma patients. However, MYCN non-amplified patients still showed heterogeneity in survival outcome. This study aimed to investigate the prognostic role of MYCN immunohistochemistry (IHC) in pre-treatment and post-treatment neuroblastoma tumors. METHODS: 215 untreated neuroblastoma tumors were stained with anti-MYCN antibody by immunohistochemical staining. 22 post-treatment tumors were used to compare MYCN staining with paired pre-treatment samples. Results were analyzed with other prognostic indicators. RESULTS: Moderate or strong expression of MYCN was associated with unfavorable survival outcomes (P < .001). Prominent staining of MYCN IHC was 95% sensitive and 95% specific for the presence of MYCN gene amplification in this study. Ten of 214 (5%) patients showed prominent MYCN staining but MYCN non-amplification, and had a poor prognosis (29.6 ± 16.4%, 5-year overall survival). Most of cases (7/11, 64%) with high or moderate MYCN expression before chemotherapy showed lower expression in their tumors after chemotherapy. CONCLUSION: MYCN protein overexpression was not only a sensitive and specific marker for MYCN gene amplification, but also a marker of poor prognosis in patients without MYCN amplification. However, MYCN protein expression was not always consistent before and after treatment.
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Amplificação de Genes , Neuroblastoma , Humanos , Lactente , Imuno-Histoquímica , Proteína Proto-Oncogênica N-Myc/genética , Proteína Proto-Oncogênica N-Myc/metabolismo , Proteína Proto-Oncogênica N-Myc/uso terapêutico , Neuroblastoma/diagnóstico , Neuroblastoma/genética , Neuroblastoma/metabolismo , PrognósticoRESUMO
Background: Intracranial atherosclerotic stenosis (ICAS) is one of the leading causes of stroke worldwide. Current diagnostic evaluations and treatments remain insufficient to assess the vulnerability of intracranial plaques and reduce the recurrence of stroke in symptomatic ICAS. On the other hand, asymptomatic ICAS is associated with an increased risk of cognitive impairment. The pathogenesis of ICAS related cognitive decline is largely unknown. The aim of SICO-ICAS study (stroke incidence and cognitive outcomes of ICAS) is to elucidate the pathophysiology of stroke and cognitive impairment in ICAS population, comprehensively evaluating the complex interactions among life-course exposure, genomic variation, vascular risk factors, cerebrovascular burden and coexisting neurodegeneration. Methods: SICO-ICAS is a multicenter, prospective, observational cohort study. We aim to recruit 3,000 patients with symptomatic or asymptomatic ICAS (>50% or occlusion) who will be followed up for ≥12 months. All participants will undergo pre-designed magnetic resonance imaging packages, blood biomarkers testing, as well as detailed cognitive domains assessment. All participants will undergo clinical visits every 6 months and telephone interviews every 3 months. The primary outcome measurement is ischemic stroke or cognitive impairment within 12 months after enrollment. Discussion: This study will establish a large prospective ICAS cohort, hopefully discover new biomarkers associated with vulnerable intracranial plaques, identify subjects at high risk for incident ischemic stroke or cognitive impairment, and eventually propose a precise diagnostic and treatment strategy for ICAS population. Trial Registration: Chinese Clinical Trials Register ChiCTR2200061938.
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Clear cell sarcoma of the kidney (CCSK) and primitive myxoid mesenchymal tumour of infancy (PMMTI) are paediatric sarcomas that most commonly harbour internal tandem duplications (ITDs) of exon 15 of the BCOR gene, in the range of 87-114 base pairs (bp). Some cases, instead, have BCOR-CCNB3 or YWHAE-NUTM2 gene fusions. About 10% of cases lack any of these genetic alterations when tested by standard methods. Two cases of CCSK and one PMMTI lacking the aforementioned mutations were analysed using Archer FusionPlex technology. Two related BCOR exon 15 RNA transcripts with ITDs of lengths 388 and 96 bp were detected in each case; only the 388 bp transcript was identified when genomic DNA was sequenced. In silico analysis of this transcript revealed acceptor and donor splice sites indicating that, at the RNA level, the 388-bp transcript was likely spliced to form the 96-bp transcript. The results were confirmed by Sanger sequencing using primers targeting the ITD breakpoint. This novel and unusually long ITD segment is difficult to identify by DNA sequencing using typical primer design strategies flanking entire duplicated segments because it exceeds the typical read lengths of most sequencing platforms as well as the usual fragment lengths obtained from formalin-fixed paraffin-embedded material. As diagnosis of CCSK and PMMTI may be challenging by morphology and immunohistochemistry alone, it is important to identify mutations in these cases. Knowledge of this novel BCOR ITD is important in relation to primer design for detection by sequencing, and using RNA versus DNA for sequencing.
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Neoplasias Renais , Sarcoma , Criança , Éxons/genética , Humanos , Neoplasias Renais/patologia , Mutação , Proteínas Proto-Oncogênicas/genética , RNA , Proteínas Repressoras/genética , Sarcoma/genética , Sarcoma/patologiaRESUMO
Background: The auxin indole-3-acetic acid (IAA) is a type of endogenous plant hormone with a low concentration in plants, but it plays an important role in their growth and development. The AUX/IAA gene family was found to be an early sensitive auxin gene with a complicated way of regulating growth and development in plants. The regulation of root growth and development by AUX/IAA family genes has been reported in Arabidopsis, rice and maize. Results: In this study, subcellular localization indicated that ZmIAA1-ZmIAA6 primarily played a role in the nucleus. A thermogram analysis showed that AUX/IAA genes were highly expressed in the roots, which was also confirmed by the maize tissue expression patterns. In maize overexpressing ZmIAA5, the length of the main root, the number of lateral roots, and the stalk height at the seedling stage were significantly increased compared with those of the wild type, while the EMS mutant zmiaa5 was significantly reduced. The total number of roots and the dry weight of maize overexpressing ZmIAA5 at the mature stage were also significantly increased compared with those of the wild type, while those of the mutant zmiaa5 was significantly reduced. Yeast one-hybrid experiments showed that ZmTCP15/16/17 could specifically bind to the ZmIAA5 promoter region. Bimolecular fluorescence complementation and yeast two-hybridization indicated an interaction between ZmIAA5 and ZmARF5. Conclusions: Taken together, the results of this study indicate that ZmIAA5 regulates maize root growth and development by interacting with ZmARF5 under the specific binding of ZmTCP15/16/17.
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Arabidopsis , Zea mays , Zea mays/genética , Saccharomyces cerevisiae/metabolismo , Raízes de Plantas/genética , Ácidos Indolacéticos/metabolismo , Arabidopsis/genética , Crescimento e DesenvolvimentoRESUMO
The symbiosis with arbuscular mycorrhizal (AM) fungi improves plants' nutrient uptake. During this process, transcription factors have been highlighted to play crucial roles. Members of the GRAS transcription factor gene family have been reported involved in AM symbiosis, but little is known about SCARECROW-LIKE3 (SCL3) genes belonging to this family in Lotus japonicus. In this study, 67 LjGRAS genes were identified from the L. japonicus genome, seven of which were clustered in the SCL3 group. Three of the seven LjGRAS genes expression levels were upregulated by AM fungal inoculation, and our biochemical results showed that the expression of LjGRAS36 was specifically induced by AM colonization. Functional loss of LjGRAS36 in mutant ljgras36 plants exhibited a significantly reduced mycorrhizal colonization rate and arbuscular size. Transcriptome analysis showed a deficiency of LjGRAS36 led to the dysregulation of the gibberellic acid signal pathway associated with AM symbiosis. Together, this study provides important insights for understanding the important potential function of SCL3 genes in regulating AM symbiotic development. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-022-01161-z.
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Circular RNAs have been identified as vital regulators to regulate the development of human cancers, including cervical cancer. Therefore, this study was designed to clarify the underlying mechanism of circASAP1 in cervical cancer. The real-time quantitative PCR assay was applied to quantify the expression levels of circASAP1, microRNA (miR)-338-3p, and ribonuclease P and MRP subunit p25 (RPP25) in cervical cancer tissues and cells. The cell proliferation ability was measured by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide and colony-forming assays. The protein expression levels of cyclin D1, proliferating cell nuclear antigen, and RPP25 were assessed by western blot assay. Flow cytometry assays were used to determine the apoptosis and cell cycle distribution of cervical cancer cells. The transwell assay was employed to test the migration and invasion abilities of cervical cancer cells. The interaction relationship between miR-338-3p and circASAP1 or RPP25 was confirmed by dual-luciferase reporter assay and RNA pull-down assay. The xenograft experiment was established to clarify the functional role of circASAP1 inhibition in vivo. CircASAP1 was overexpressed in cervical cancer tissues and cells compared with negative groups. Additionally, the loss-of-functional experiments implied that knockdown of circASAP1 impeded proliferation, migration, and invasion while induced apoptosis and cell cycle arrest in cervical cancer cells along with repressed tumor growth in vivo through regulation of miR-338-3p. In addition, RPP25 was a target mRNA of miR-338-3p, and overexpression of miR-338-3p suppressed proliferation, migration, and invasion while induced apoptosis and cell cycle arrest in cervical cancer cells by suppressing RPP25 expression. Mechanistically, circASAP1 could function as a sponge for miR-338-3p to increase the expression of RPP25, and further regulated proliferation, migration, invasion, apoptosis, and cell cycle program of cervical cancer cells, which might be potential markers for cervical cancer diagnosis.
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Proteínas Adaptadoras de Transdução de Sinal/farmacologia , MicroRNAs/efeitos dos fármacos , RNA Circular/farmacologia , Ribonuclease P/efeitos dos fármacos , Neoplasias do Colo do Útero/patologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
METHODS: Individualized treatment of traditional Chinese medicine (TCM) provides a theoretical basis for the study of the personalized classification of complex diseases. Utilizing the TCM clinical electronic medical records (EMRs) of 7170 in patients with IS, a patient similarity network (PSN) with shared symptoms was constructed. Next, patient subgroups were identified using community detection methods and enrichment analyses were performed. Finally, genetic data of symptoms, herbs, and drugs were used for pathway and GO analysis to explore the characteristics of pathways of subgroups and to compare the similarities and differences in genetic pathways of herbs and drugs from the perspective of molecular pathways of symptoms. RESULTS: We identified 34 patient modules from the PSN, of which 7 modules include 98.48% of the whole cases. The 7 patient subgroups have their own characteristics of risk factors, complications, and comorbidities and the underlying genetic pathways of symptoms, drugs, and herbs. Each subgroup has the largest number of herb pathways. For specific symptom pathways, the number of herb pathways is more than that of drugs. CONCLUSION: The research of disease classification based on community detection of symptom-shared patient networks is practical; the common molecular pathway of symptoms and herbs reflects the rationality of TCM herbs on symptoms and the wide range of therapeutic targets.
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OBJECTIVE: Denys-Drash syndrome (DDS) is defined by the triad of Wilms tumor, nephrotic syndrome, and/or ambiguous genitalia. Genetic testing may help identify new gene mutation sites and play an important role in clinical decision-making. METHODS: We present a patient with an XY karyotype and female appearance, nephropathy, and Wilms tumor in the right kidney. Genomic DNA was extracted from peripheral blood cells according to standard protocols. "Next-generation" sequencing (NGS) was performed to identify novel variants. The variant was analyzed with Mutation Taster, and its function was explored by a cell growth inhibition assay. RESULTS: We found the first case of Denys-Drash syndrome with the uncommon missense mutation (c.1420C>T, p.His474 Tyr) in the WT1 gene. In silico analysis, the variant was predicted "disease-causing" by Mutation Taster. The mutated variant showed a weaker effect in inhibiting tumor cells than wild-type WT1. CONCLUSIONS: The uncommon missense mutation (c.1420C>T, p.His474 Tyr) in the WT1 gene may be a crucial marker in DDS.
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Povo Asiático/genética , Síndrome de Denys-Drash/genética , Proteínas WT1/genética , Tumor de Wilms/genética , Sequência de Aminoácidos , Sequência de Bases , Linhagem Celular Tumoral , China , Simulação por Computador , Feminino , Seguimentos , Humanos , Lactente , Laparoscopia , Mutação , Linhagem , Tomografia Computadorizada por Raios X , Proteínas WT1/química , Tumor de Wilms/diagnóstico , Tumor de Wilms/diagnóstico por imagemRESUMO
AIMS: Congenital mesoblastic nephroma (CMN) is histologically classified into classic, cellular and mixed subtypes. The aims of this study were to characterise the clinical, pathological and molecular features of a series of CMNs, and to determine the utility of pan-Trk and epidermal growth factor receptor (EGFR) immunohistochemistry as surrogate markers for NTRK gene fusions and EGFR internal tandem duplications (ITDs). METHODS AND RESULTS: Twenty-two archival CMN cases (12 classic, five cellular, and five mixed) were tested for the ETV6-NTRK3 fusion and EGFR ITD transcripts by the use of reverse transcriptase polymerase chain reaction (PCR), and next-generation sequencing-based anchored multiplex PCR. All 12 classic CMNs had EGFR ITD. Of the five cellular CMNs, four had the ETV6-NTRK3 fusion and one had the KLHL7-BRAF fusion. Of the five mixed CMNs, four had EGFR ITD, and one had the ETV6-NTRK3 fusion. Pan-Trk immunoreactivity was 100% sensitive and 94.1% specific for the presence of NTRK rearrangement. However, EGFR staining was only 62.5% sensitive and 33.3% specific for EGFR ITD. CONCLUSIONS: EGFR ITD is a consistent genetic event in classic CMN. A majority of cellular CMNs have the ETV6-NTRK3 fusion. Rare cellular CMNs may harbour non-canonical mutations such as the KLHL7-BRAF fusion, which was found in one case. Mixed CMNs may have either EGFR ITD or the ETV6-NTRK3 fusion. Pan-Trk immunohistochemistry is a sensitive, albeit not perfectly specific, marker for NTRK rearrangement. EGFR immunohistochemistry is not helpful as a marker of EGFR ITD.
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Autoantígenos/genética , Neoplasias Renais/genética , Nefroma Mesoblástico/genética , Proteínas de Fusão Oncogênica/genética , Proteínas Proto-Oncogênicas B-raf/genética , Receptores ErbB/genética , Feminino , Duplicação Gênica , Humanos , Lactente , Recém-Nascido , Masculino , Mutação , Fusão OncogênicaRESUMO
Primary glomus tumors of the kidney are rare and have never been reported in children under 16 years of age. Tuberous sclerosis complex (TSC) is an extremely variable genetic condition that can affect virtually any organ in the body. Only a single case of glomus tumor associated with TSC was reported in 1964. In this article, we describe the clinical, radiologic, and pathological features of a primary renal glomus tumor in an 8-year-old girl with TSC. This tumor is large, has a deep location, and has infiltrative margins and numerous mitoses. However, there was no disease progression in a 16-month period of follow-up. To our knowledge, this is the second report of primary renal glomus tumor in childhood, the youngest one in the literature.