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1.
J Pediatr Hematol Oncol ; 46(5): e327-e330, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38748615

RESUMO

BACKGROUND: The occurrence of hemophagocytic lymphohistiocytosis (HLH) in patients with subcutaneous panniculitis-like T-cell lymphoma (SPTCL) may be due to HAVCR2 gene mutation, leading to T-cell immunoglobulin and mucin domain-containing molecule 3 deficiency, T-cell and macrophage activation, and proinflammatory cytokine production. OBSERVATION: We report a patient with SPTCL and HLH for whom ruxolitinib, used as a novel treatment, showed notable therapeutic effects. CONCLUSIONS: Remission of both HAVCR2 mutation-induced high inflammatory characteristics and significant symptoms post-ruxolitinib administration suggested that patients with SPTCL and HLH may not represent typical lymphoma cases. Ruxolitinib, with its relatively low toxic side effects, can provide favorable outcomes.


Assuntos
Receptor Celular 2 do Vírus da Hepatite A , Linfoma de Células T , Mutação , Nitrilas , Paniculite , Pirazóis , Pirimidinas , Humanos , Pirazóis/uso terapêutico , Paniculite/genética , Paniculite/tratamento farmacológico , Paniculite/patologia , Linfoma de Células T/tratamento farmacológico , Linfoma de Células T/genética , Linfoma de Células T/patologia , Receptor Celular 2 do Vírus da Hepatite A/genética , Pirimidinas/uso terapêutico , Linfo-Histiocitose Hemofagocítica/genética , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/patologia , Masculino , Criança , Feminino
2.
Br J Haematol ; 202(1): 135-146, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37062931

RESUMO

Frequent germline mutations of HAVCR2, recently identified in subcutaneous panniculitis-like T-cell lymphoma (SPTCL), are associated with an increased risk of hemophagocytic lymphohistiocytosis (HLH). However, SPTCL-HLH represents a challenge because of the difficulties in treatment with poor survival. Its malignant nature, specifically harbouring HAVCR2 mutations, has also been questioned. To better understand its pathology and treatment, we analysed the clinical data of six patients diagnosed at our centre. The median age at onset was 10.5 years (range, 0.8-12.4). Five patients presented with skin lesions of subcutaneous nodules/plaques and/or ulceration. All patients developed HLH; notably, one infant only had HLH without skin involvement. Histopathologically, only two patients were diagnosed with SPTCL and three were reported as panniculitis with no sufficient evidence of lymphoma. Genetically, germline homozygous mutation of HAVCR2 (p.Y82C) was identified in all patients, with a median diagnosis time of 4.6 months. All patients initially received corticosteroids, immunosuppressants or chemotherapy, achieving unfavourable responses. Strikingly, they responded well to ruxolitinib targeting inflammatory cytokines, allowing rapid disease resolution and/or long-term maintenance of remission. The excellent efficacy of ruxolitinib highlights this disease as an inflammatory condition instead of neoplastic nature and indicates novel agents targeting key inflammatory pathways as an encouraging approach for this disease entity.


Assuntos
Linfo-Histiocitose Hemofagocítica , Paniculite , Criança , Pré-Escolar , Humanos , Lactente , Mutação em Linhagem Germinativa , Receptor Celular 2 do Vírus da Hepatite A/genética , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/genética , Linfo-Histiocitose Hemofagocítica/complicações , Paniculite/tratamento farmacológico , Paniculite/genética
3.
Fetal Pediatr Pathol ; 41(3): 499-504, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33213248

RESUMO

Background: Extraskeletal Ewing's Sarcoma (EES) may harbor more than one tumor-specific genetic abnormality, leading to diagnostic difficulties. Case report: We report a nine-year-old boy with recurrent mass of his right thigh. Tumor cells were round, with scant cytoplasm, finely dispersed chromatin, and inapparent, small nucleoli. The initial misdiagnosis was T-lymphoblastic lymphoma due to CD7 and TCR/Ig monoclonal rearrangement. As it expressed NKX2.2 and harbored an EWSR1-FLI1 fusion transcript, the diagnosis was changed to EES. The child underwent EES therapy with good initial response, but had a subcutaneous relapse at 22 months. Conclusion: In addition to typical genetic alterations, Ewing sarcoma can also express CD7 and TCR/Ig rearrangement, which are not limited to lymphoma.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras , Sarcoma de Ewing , Criança , Humanos , Imunoglobulinas , Masculino , Recidiva Local de Neoplasia , Receptores de Antígenos de Linfócitos T , Sarcoma de Ewing/diagnóstico , Sarcoma de Ewing/genética , Sarcoma de Ewing/patologia
4.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(5): 859-861, 2021 Sep.
Artigo em Zh | MEDLINE | ID: mdl-34622606

RESUMO

In this study, we report on three immunocompetent children with pulmonary cryptococcosis presenting mediastinal lymphadenopathy as the prominent manifestation. All three children were otherwise healthy previously. Two children had a history of exposure to pigeons and poultry. All three presented persistent fever accompanied by mild cough. There were no obvious positive signs in the lungs. One patient had enlarged cervical lymph nodes. All three had elevated levels of white blood cells, neutrophil count, and C-reactive protein (CRP). The levels of IgG, IgM, IgA, IgE and T cell subsets were normal in all cases, and they were all tested negative for HIV antibody. Two children were tested positive for serum cryptococcal antigen (sCRAG). The chest X-ray and pulmonary CT findings of the three patients all demonstrated marked enlargement of mediastinal lymph nodes, and one patient had nodules in the parenchyma. Surgical biopsies of mediastinal lymph nodes were performed in two children and large numbers of capsule spores were found in the histological examination. In the three cases, definitive diagnosis of pulmonary cryptococcosis were made in two patients, and clinical diagnosis was made in the third patient. Two patients were treated with fluconazole alone. The other patient whose condition was complicated with spleen infection was treated with fluconazole combined with amphotericin B for the first month, and was then given fluconazole for maintenance treatment. The overall treatment course lasted 5-9 months and all three were cured eventually. In conclusion, immunocompetent children with pulmonary cryptococcosis may present mediastinal lymphadenopathy as a prominent or isolated manifestation, which should be considered in differential diagnosis. Treatment with fluconazole alone or in combination with amphotericin B when it was necessary showed good therapeutic outcomes.


Assuntos
Criptococose , Linfadenopatia , Criança , Tosse , Criptococose/complicações , Criptococose/diagnóstico , Criptococose/tratamento farmacológico , Humanos , Pulmão , Linfonodos
5.
J Clin Immunol ; 40(1): 114-122, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31705453

RESUMO

PURPOSE: STING-associated vasculopathy with onset in infancy (SAVI) is a new rare auto-inflammatory disease. The purpose of this study is to report new cases and summarize the manifestations and outcome of SAVI. METHODS: We made a retrospective analysis of three pediatric patients diagnosed with SAVI between March 2016 and July 2018 in Beijing Children's Hospital. RESULTS: Three patients comprised one boy and two girls. The median age of onset was 4 months. All patients had the same de novo heterozygous mutation (c.463G>A, p. V155M) of TMEM173. All patients presented with interstitial lung disease and one coexisted with diffuse alveolar hemorrhage. Rashes were presented in two patients. Other clinical manifestations include febrile attacks, failure to thrive, arthritis, myositis, cerebrovascular involvement, ureteral calculus, gastroesophageal reflux, and malnutrition. Ground-glass opacities were the most common features of chest computed tomography, followed with cysts and reticular opacities. Transbronchial lung biopsy was performed in one patient revealing pulmonary vasculitis. Skin biopsy was performed in one patient with changes of vasculitis. All patients were treated with corticosteroids and two patients received combined treatment of tofacitinib. The therapeutic effects of tofacitinib were limited on interstitial lung disease in both patients and were poor on rashes in one patient. One patient under the treatment of tofacitinib died. CONCLUSIONS: New clinical aspect of diffuse alveolar hemorrhage is first reported to be associated with SAVI. Unsatisfactory therapeutic effects of tofacitinib are observed in this study and further evaluations are needed.


Assuntos
Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/genética , Proteínas de Membrana/genética , Piperidinas/uso terapêutico , Pirimidinas/uso terapêutico , Doenças Vasculares/tratamento farmacológico , Doenças Vasculares/genética , Pré-Escolar , Feminino , Hemorragia/tratamento farmacológico , Hemorragia/genética , Humanos , Lactente , Inflamação/tratamento farmacológico , Inflamação/genética , Pulmão/efeitos dos fármacos , Masculino , Mutação/genética , Estudos Retrospectivos , Pele/efeitos dos fármacos
6.
Int J Mol Sci ; 21(4)2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32075313

RESUMO

WRKY transcription factors play central roles in developmental processes and stress responses of wheat. Most WRKY proteins of the same group (Group III) have a similar function in abiotic stress responses in plants. TaWRKY46, a member of Group III, was up-regulated by PEG treatment. TaWRKY46-GFP fusion proteins localize to the nucleus in wheat mesophyll protoplasts. Overexpression of TaWRKY46 enhanced osmotic stress tolerance in transgenic Arabidopsis thaliana plants, which was mainly demonstrated by transgenic Arabidopsis plants forming higher germination rate and longer root length on 1/2 Murashige and Skoog (MS) medium containing mannitol. Furthermore, the expression of several stress-related genes (P5CS1, RD29B, DREB2A, ABF3, CBF2, and CBF3) was significantly increased in TaWRKY46-overexpressing transgenic Arabidopsis plants after mannitol treatment. Taken together, these findings proposed that TaWRKY46 possesses vital functions in improving drought tolerance through ABA-dependent and ABA-independent pathways when plants are exposed to adverse osmotic conditions. TaWRKY46 can be taken as a candidate gene for transgenic breeding against osmotic stress in wheat. It can further complement and improve the information of the WRKY family members of Group III.


Assuntos
Proteínas de Arabidopsis/genética , Pressão Osmótica/fisiologia , Plantas Geneticamente Modificadas/genética , Fatores de Transcrição/genética , Triticum/genética , Arabidopsis/genética , Secas , Regulação da Expressão Gênica de Plantas , Germinação/genética , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , Protoplastos/metabolismo , Estresse Fisiológico/genética
7.
Ecotoxicol Environ Saf ; 173: 214-224, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-30772711

RESUMO

The enrichment of Cadmium in vegetables is threatening human health. The study aimed to screen Cd low-enriched leafy vegetables and explore whether antioxidative enzymes and heavy metal chelators are synergistic defensive mechanisms. In this paper, the Cd accumulation and translocation of garland chrysanthemum (Chrysanthemum coronarium L.), spinach (Spinacia oleracea L.), and lettuce (Lactuca sativa L.) were examined by soil pot culture and hydroponic experiments. The responses of oxidative stress markers, antioxidative enzymes activity, and thiol pool (cysteine, γ-glutamylcysteine, glutathione, and phytochelatins) content to Cd stress were assayed. The results showed that Garland chrysanthemum was Cd low-uptake species. The soil Cd safety thresholds for spinach, lettuce, and garland chrysanthemum were 0.41, 0.49, and 9.10 mg kg-1, respectively. The order of root phytochelatins (PCs) concentration was consistent with that of plant tolerance index (TI): garland chrysanthemum > spinach > lettuce. While the order of the ratio of shoot Cd to root Cd (SR ratio) was exactly the opposite of that of TI. In lettuce root, activity of superoxide dismutase, peroxidase, and catalase decreased significantly under Cd stress. Nevertheless those parameters in the roots of spinach and lettuce maintained steady, or even enhanced. In conclusion, the Cd translocation and partition in plant, antioxidative defense, and PCs homeostasis played an important role in the Cd tolerance of vegetables.


Assuntos
Cádmio/toxicidade , Chrysanthemum/efeitos dos fármacos , Lactuca/efeitos dos fármacos , Poluentes do Solo/toxicidade , Spinacia oleracea/efeitos dos fármacos , Catalase/metabolismo , Chrysanthemum/metabolismo , Glutationa/metabolismo , Lactuca/metabolismo , Estresse Oxidativo , Peroxidases/metabolismo , Fitoquelatinas/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Brotos de Planta/efeitos dos fármacos , Brotos de Planta/metabolismo , Spinacia oleracea/metabolismo , Compostos de Sulfidrila/metabolismo , Superóxido Dismutase/metabolismo , Verduras/efeitos dos fármacos , Verduras/metabolismo
9.
BMC Pediatr ; 18(1): 382, 2018 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-30514248

RESUMO

BACKGROUND: Mediastinal teratoma is uncommon in children. It can be very difficult to diagnose especially in early stage. Rarely, teratoma may rupture into adjacent structures and lead to lung lesions or pleuritis. The main rarity of our reported cases was the dynamic imaging findings very similar to the developmental process of tuberculosis in patients 1 and 2, the pachypleuritis in patients 2 and 3, the extremely elevated inflammatory markers very similar to empyema in patient 3, and the extremely atypical tumor shape in all patients. CASE PRESENTATION: We present three pediatric patients presenting predominantly with recurrent hemoptysis and/or chest pain who were ultimately diagnosed with mediastinal teratoma containing pancreatic tissue. All three patients were initially suspected to have tuberculosis or empyema, and underwent relevant treatment, but without improvement. Patient 1 had left hilar enlargement, and subsequently an enlarging calcified cavity within high-density consolidation was identified. Patient 2 initially presented with right-sided pulmonary consolidation and pleuritis, and subsequently developed right lower lobe calcification, pleural thickening, and irregular soft tissue in the right inferior mediastinum. Patient 3 was initially found to have right lobe consolidation accompanied by a massive right-sided pleural effusion with extremely elevated inflammatory markers in serum and pleural effusion. The effusion later acquired heterogeneous density and appeared to become encapsulated. In patients 2 and 3, pleural biopsy identified fibrous tissue (with and without granuloma). Thoracotomy/thoracoscopy revealed mediastinal teratoma in each case, all of which were completely excised and the patients made uneventful recoveries. Histopathologic analysis revealed mature cystic-solid teratoma containing pancreatic tissue in all patients, and calcification in patients 1 and 2. CONCLUSIONS: Clinicians should be mindful that mediastinal teratoma is a potential cause of hemoptysis, lung lesions and pleuritis. Calcification and pachypleuritis on chest imaging especially in patients without fever should be highly suspected of mediastinal teratoma. Pleural biopsy sometimes fails to assist in making a definitive diagnosis.


Assuntos
Erros de Diagnóstico , Empiema Pleural/diagnóstico , Hemoptise/etiologia , Neoplasias do Mediastino/diagnóstico por imagem , Pleurisia/etiologia , Teratoma/diagnóstico por imagem , Tuberculose Pleural/diagnóstico , Biópsia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Neoplasias do Mediastino/patologia , Neoplasias do Mediastino/cirurgia , Recidiva , Teratoma/patologia , Teratoma/cirurgia , Toracoscopia , Toracotomia , Tomografia Computadorizada por Raios X
11.
J Asthma ; 51(10): 1043-8, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24986248

RESUMO

OBJECTIVE: Identification of young children who are likely to have multi-trigger wheezing is very important for early diagnosis and treatment of asthma. We investigate an index for predicting multi-trigger wheezing in infants with first episode of wheezing. METHODS: One-hundred twenty-eight infants (2-20 months) with first episode of wheezing were followed for two years. Personal and family history of atopic diseases was recorded. Wheezing severity was evaluated using the Preschool Respiratory Assessment Measure. Sputum samples were collected from patients, stained with hematoxylin and eosin and studied by optical microscopy. The largest Creola body in sputum was located and the number of shed exfoliated airway epithelial cells (EAECs) counted. Recurrent wheezing was observed and classified as multi-trigger wheezing or non-multi-trigger wheezing. The predictive value of EAECs, family or personal history of atopic disease and the severity of wheezing for subsequent development of multi-trigger wheezing was analyzed. RESULTS: Better predictive performance was achieved by considering the three measures together than by considering each separately. Receiver operator characteristic analysis showed that an index combining wheezing severity score of 9495 sputum EAECs and a family or personal history of atopic disease had a sensitivity of 95.1%, specificity of 74.2%, a positive predictive value of 58.6% and a negative predictive value of 93.6% for prediction of multi-trigger wheezing. CONCLUSION: For infants with first episode of wheezing, wheezing severity score, family or personal history of atopic disease and number of EAECs in sputum can predict future multi-trigger wheezing.


Assuntos
Asma/fisiopatologia , Sons Respiratórios/fisiopatologia , Área Sob a Curva , Asma/diagnóstico , Asma/etiologia , Asma/patologia , Células Epiteliais/imunologia , Células Epiteliais/patologia , Humanos , Lactente , Modelos Logísticos , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Sons Respiratórios/etiologia , Sons Respiratórios/imunologia , Escarro
12.
Zhonghua Bing Li Xue Za Zhi ; 43(8): 541-5, 2014 Aug.
Artigo em Zh | MEDLINE | ID: mdl-25346125

RESUMO

OBJECTIVE: To correlate the abnormal expression of anapastic lymphoma kinase (ALK) protein with the genetic and epigenetic changes of ALK, and to analyze its clinical application in pediatric neuroblastoma. METHODS: Three neuroblastoma (NB) cell lines (two ALK positive: SH-SY5Y and SK-N-SH, one ALK negative: SK-N-AS) and 43 paraffin-embedded NB tissues were included in the study. In both cell lines and clinical cases, immunohistochemistry was used to detect ALK protein expression; PCR and Sanger sequencing were used to detect ALK point mutation; fluorescence in situ hybridization (FISH) was used to detect ALK abnormality and bisulfite sequencing PCR (BSP) was used to detect methylation of CpG island in the promoter area of ALK. RESULTS: The cell lines SH-SY5Y and SK-N-SH were positive for ALK expression (cytoplasm), while the SK-N-AS was negative; among the 43 cases of NB, 26 (60.5%, 26/43) were positive for ALK protein (membrane and cytoplasm), and the rest were negative. Survival analysis showed ALK protein expression was related to survival time, with ALK positive cases having shorter survival time than ALK negative cases (P = 0.020). But ALK protein expression had no association with tumor differentiation (P = 0.503), tumor sites (P = 1.000) and age of patients (P = 0.063). FISH showed ALK amplification in two cases (4.6%, 2/43), ALK gain was found in 30 cases (69.7%, 30/43), and the remaining cases had normal ALK copy (25.6%, 11/43). The presence of extra copies (amplification and gain) of ALK was associated with ALK positive protein expression (P = 0.020), but there was no association with tumor differentiation (P = 1.000), tumor sites (P = 0.775) and age of patients (P = 0.328). No point mutation was found in all three cell lines. Of the 43 NB cases, only one case (2.3%, 1/43) showed point mutation in exon 23, and was a synonymous mutation [A1200A (G4552C)]. The case was ALK negative, but the patient died two months after diagnosis. BSP analysis showed that CpG island in ALK promoter region were all unmethylated in three cell lines and 6 NB cases (including 3 ALK positive, 3 ALK negative). CONCLUSIONS: ALK protein is expressed in most NB, and the expression indicates poor outcome. ALK expression is associated with extra copies of ALK, but there is no association with the methylation status of CpG island of ALK; the presence of extra copies of ALK is the most common genetic aberration in NB. Point mutation of ALK is rare, and may predict poor prognosis in pediatric NB.


Assuntos
Neuroblastoma/genética , Receptores Proteína Tirosina Quinases/genética , Adolescente , Quinase do Linfoma Anaplásico , Linhagem Celular Tumoral , Criança , Éxons , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Neuroblastoma/enzimologia , Receptores Proteína Tirosina Quinases/metabolismo
13.
Zhonghua Bing Li Xue Za Zhi ; 43(11): 747-52, 2014 Nov.
Artigo em Zh | MEDLINE | ID: mdl-25582253

RESUMO

OBJECTIVE: To study the clinicopathological and immunohistochemical features, histogenesis and prognosis of pleuropulmonary blastoma (PPB) in children. METHODS: PPB specimens from 16 pediatric cases with an age ranging from 1 year and 7 months to 5 years and 3 months (mean age of 3 years) were retrieved and analyzed by routine histological, immunohistochemical and electron methods. RESULTS: Among 16 patients, there were 2 type I, 7 type II and 7 type III PPB cases. Type I PPB as multilocular cystic structure, consisted of thin fibrous wall lining the respiratory epithelium, subepithelial primitive blastema or immature mesenchymal cells, with or without rhabdomyoblastic differentiation or cartilage; Type II PPB as cystic-solid tumor, comparing with type I, consisted of intracystic components with appearance of anaplastic tumor cells. Type III PPB consisted of completely solid mass, the same as the solid region of type II, had mixed pattern including blastema, undifferentiated spindle-cell proliferations and sarcomas. In addition, anaplastic tumor cells and intra-and extra- cytoplasmic eosinophilic globules were also commonly present. Epithelial components in PPB were benign. Immunohistochemical study showed primitive mesenchymal differentiation of tumors. All cases were positive for vimentin, desmin, myogenin and SMA in tumors with skeletal muscle differentiation, S-100 was positive in tumors with cartilage differentiation. All tumors were negative for synaptophysin, CD99, and CD117. Benign epithelial components were positive for AE1/AE3 and EMA. In 12 cases, electron microscopy revealed few organelles in the primitive mesenchymal cells and rich heterochromatin in mesenchymal cells, the latter also demonstrating cytoplasmic myofilament dysplasia. Nine cases had clinical follow-up ranging from 5 to 48 months, of which 4 patients died. CONCLUSIONS: PPB is a rare lung neoplasm of children under the age of 6 years, with distinct pathological morphology. PPB may arise from lung or pleura mesenchymal cells and has a poor clinical outcome.


Assuntos
Neoplasias Pulmonares/patologia , Blastoma Pulmonar/patologia , Pré-Escolar , Cistos/patologia , Desmina/análise , Feminino , Humanos , Lactente , Neoplasias Pulmonares/química , Masculino , Microscopia Eletrônica , Miogenina/análise , Prognóstico , Blastoma Pulmonar/química , Sarcoma/patologia , Vimentina/análise
14.
Int J Pediatr Otorhinolaryngol ; 177: 111872, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38286078

RESUMO

PURPOSE: Vocal cord paralysis has been reported as a common complication of button battery (BB) ingestion, and there is a need to confirm the mechanism of vocal cord paralysis for the development of a standardized treatment. METHODS: A new CR2032 BB and artificial saliva were placed in a fresh pig esophagus with the recurrent laryngeal nerve (RLN); the negative electrode faced the nerve in the experimental group, while the positive electrode faced the nerve in the control group. The pH values of the intra- and extraesophageal walls were measured simultaneously. Pathological examination was performed after the esophagus and nerves were damaged. RESULTS: After BB ingestion, the pH near the intraesophageal negative electrode increased rapidly, reaching 11.5 at 30 min and over 14 at 6 h, while the extraesophageal pH did not change at 1 h and began to accelerate after 2 h, reaching 10 at 6 h. After 6 h of exposure, the pathological section showed that the structure of the mucosa, submucosa, and muscle layer were destroyed; chromatin in the nucleus faded, and part of the nerve bundle in the adventitia had liquefaction necrosis. CONCLUSION: The basic mechanism of vocal cord paralysis caused by BB ingestion is that the OH- generated by the electrolytic reaction of the negative electrode penetrates the esophageal wall and corrodes the RLN, which may be the cause of vocal cord paralysis caused by BB ingestion without esophageal perforation.


Assuntos
Paralisia das Pregas Vocais , Criança , Humanos , Animais , Suínos , Paralisia das Pregas Vocais/etiologia , Paralisia das Pregas Vocais/patologia , Esôfago/patologia , Fontes de Energia Elétrica , Necrose , Nervo Laríngeo Recorrente , Ingestão de Alimentos
15.
J Pediatr (Rio J) ; 100(4): 384-391, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38547930

RESUMO

OBJECTIVE: To investigate the incidence, clinical and genetic characteristics of pediatric lymphoma patients of China with inborn errors of immunity (IEI)-related gene mutations, which have not been fully studied. METHOD: From Jan. 2020 to Mar. 2023, IEI-related genetic mutations were retrospectively explored in 108 children with lymphomas admitted to Beijing Children's Hospital by NGS. Genetic rule and clinical characteristics as well as treatment outcomes were compared between patients with or without IEI-related gene mutations. RESULTS: A total of 17 patients (15.7 %) harbored IEI-associated mutations, including 4 cases with X-linked lymphoproliferative syndrome (XLP), 3 cases had mutations in tumor necrosis factor receptor superfamily 13B (TNFRSF13B), 2 cases with Activated p110 syndrome (APDS). Patients with IEI all had alteration of immunocompetence with decreased levels of immunoglobulin and lymphocyte subsets. Recurrent infection existed in 41.2 % of patients. The 18-month event-free survival (EFS) and the overall response rate (ORR) of patients with IEI are significantly lower than those without IEI (33.86% vs. 73.26 %, p = 0.011; 52.94% vs. 87.91 %, p = 0.002, respectively). In addition, patients with IEI had a higher progression disease (PD) rate of 23.5 % than those without IEI of 4.4 % (p = 0.006). CONCLUSION: The present study demonstrated that IEI-associated lymphomas were much more common than originally appreciated in pediatric lymphomas, and those were insensitive to treatment and more likely to progress or relapse. The genomic analysis and a thorough review of the medical history of IEI can be used to distinguish them from pediatric lymphomas without IEI, which are beneficial for the early diagnosis and direct intervention.


Assuntos
Linfoma , Mutação , Humanos , Masculino , Feminino , Estudos Retrospectivos , Criança , China/epidemiologia , Linfoma/imunologia , Linfoma/genética , Pré-Escolar , Lactente , Adolescente , Relevância Clínica
16.
Exp Mol Pathol ; 95(2): 124-30, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23797004

RESUMO

BACKGROUND: ALK gene has been identified as a major neuroblastoma (NBL) predisposition gene. But ALK gene copy number and protein expression in ganglioneuroblastoma (GNBL) and ganglioneuroma (GN) are poorly described in the literature. Furthermore, there are controversies on the correlation between ALK protein expression and clinical outcome in NBL. METHODS: We evaluated MYCN/ALK gene copy number by fluorescence in situ hybridization (FISH) and detected ALK protein expression by immunohistochemistry (IHC) in 188 NBL, 52 GNBL and 6 GN samples and analyzed their association with clinical outcome of the patients. RESULTS: Although ALK gene copy number increase is a recurrent genetic aberration of neuroblastic tumors (NTs) (39.1%, 96/246), ALK amplification was only present in three NBLs (1.2%, 3/246). The frequency of ALK positivity in NBL (50.5%, 51/101) was significantly higher than in GNBL (22.6%, 7/31) and in GN (0.0%, 0/4) (P<0.05). In addition, ALK positivity also significantly correlates with MYCN/ALK gene copy number increases (P<0.05). Kaplan-Meier survival analysis indicated that MYCN/ALK amplification is correlated with decreased overall survival in NBL. A better prognosis trend was observed in patients with MYCN/ALK gain tumors compared with those with MYCN/ALK normal tumors. Furthermore, ALK positivity significantly correlated with inferior survival in NBL (P=0.044). CONCLUSION: ALK positivity in NTs correlated with advanced tumor types and MYCN/ALK gene copy number increases. ALK positivity predicts inferior prognosis in NBL and IHC is a simplified strategy to screen ALK positivity in clinical practice.


Assuntos
Amplificação de Genes , Neuroblastoma/genética , Neuroblastoma/mortalidade , Receptores Proteína Tirosina Quinases/biossíntese , Receptores Proteína Tirosina Quinases/genética , Quinase do Linfoma Anaplásico , Criança , Pré-Escolar , Feminino , Dosagem de Genes , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Lactente , Estimativa de Kaplan-Meier , Masculino , Neuroblastoma/metabolismo , Prognóstico
17.
Zhonghua Bing Li Xue Za Zhi ; 42(5): 299-304, 2013 May.
Artigo em Zh | MEDLINE | ID: mdl-24004585

RESUMO

OBJECTIVE: To investigate the molecular genetic abnormalities of N-myc and C-myc, and their clinical pathological implications in pediatric neuroblastic tumors (NTs). METHODS: Abnormalities of N-myc were detected by interphase fluorescence in situ hybridization (FISH) technique in 246 cases of NTs, including neuroblastoma (NB,188 cases), ganglioneuroblastoma (GNB, 52 cases), ganglioneuroma (GN, 6 cases), and their association with the histological typing of the tumors and prognosis was analyzed. Abnormalities of C-myc were detected by FISH in 133 cases of NTs. RESULTS: Of the 246 cases of NTs, N-myc amplification was only found in 27 cases (11.0%, 27/246) of NB, but not in any cases of GNB or GN (P < 0.05). 89.0% (219/246) N-myc non-amplification were found in NTs, and it included N-myc gain in 175 cases (71.1%, 175/246) and normal N-myc in 44 cases (17.9%, 44/246). Univariate analysis indicated significantly (P = 0.012) poorer outcome in patients with N-myc amplification than N-myc non-amplification. However no significant difference was observed between N-myc gain cases and normal N-myc cases (P = 0.057). C-myc gain was found in 74 of 133 cases (55.6%) of NTs; no C-myc amplification or translocation was detected. Forty percent (6/15) of cases with N-myc amplification and 57.6% (68/118) of cases with N-myc non-amplification were accompanied by C-myc gain. The difference between N-myc amplification and non-amplification with C-myc gain was not significant (P > 0.05). Univariate analysis indicated that the outcome difference was not statistically significant between C-myc gain cases and normal C-myc cases (P = 0.357). CONCLUSIONS: The incidence of N-myc amplification only found in NB is low in pediatric NTs in China. Patients with N-myc amplification predict poorer outcome. No amplification or translocation of C-myc is detected in NTs, whereas C-myc gain is relatively common in NTs. There is no obvious association between N-myc amplification and C-myc gain.


Assuntos
Neoplasias das Glândulas Suprarrenais/patologia , Amplificação de Genes , Genes myc , Neuroblastoma/patologia , Neoplasias das Glândulas Suprarrenais/genética , Criança , Pré-Escolar , Feminino , Seguimentos , Ganglioneuroblastoma/genética , Ganglioneuroblastoma/patologia , Ganglioneuroma/genética , Ganglioneuroma/patologia , Humanos , Hibridização in Situ Fluorescente , Lactente , Masculino , Neoplasias do Mediastino/genética , Neoplasias do Mediastino/patologia , Neuroblastoma/genética , Taxa de Sobrevida
18.
Heliyon ; 9(10): e21136, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37886759

RESUMO

Ear photosynthesis plays a key role in wheat photosynthesis during the grain filling stage, particularly under drought stress. Thus, dissecting the responsibilities of the glume and awn in photosynthetic carbon fixation and assimilates transportation during the grain filling stage in spikes is imperative. In this study, the detachment of the glume (DG) and awn (DA) of a wheat variety (Pubing143) was used to estimate their influences on ear photosynthesis and dry matter distribution. Radioactive carbon-14 (14C) isotope was detected by a multifunctional liquid scintillation counting system. The accumulation of 14C assimilates and their contributions to grain weight were then calculated. Under well-watered conditions, ear photosynthesis was reduced by 16.8 % and 46.2 % 25 d after anthesis (DAA) in the de-glumed control (DGC) and de-awned control (DAC) treatments, respectively, compared with the intact ear control (IEC). Under drought stress, ear photosynthesis was reduced by 46 % and 74.2 % at 25 DAA after removing the glume and awn, respectively. Under normal conditions, the number of 14C assimilates of DGC, and DAC was reduced by 14.6 % and 20.9 % in grains at 25 DAA, respectively, compared with the IEC. Compared with IED, the 14C assimilates of DGD, and DAD declined by 17.2 % and 27 %, respectively, in grains at 25 DAA under drought conditions. Under well-watered conditions, the grain weight per pot was reduced by 11.2 % and 25.4 % in the de-glumed control (DGC) and de-awned control (DAC) treatments, respectively, compared with the intact ear control (IEC). The grain weight per pot was further reduced after removing the glume and awn (16 % and 32.2 %, respectively) under drought stress. Furthermore, the awn contribution to grain weight was twice that of the glume. Our results suggest that the glume and awn of ears play prominent roles during grain filling in wheat, especially under drought stress, and that the awn is more crucial than the glume.

19.
Ying Yong Sheng Tai Xue Bao ; 34(2): 442-450, 2023 Feb.
Artigo em Zh | MEDLINE | ID: mdl-36803722

RESUMO

The effects of nitrogen fertilizer and biochar on topsoil quality in the drylands of northwest China were studied in field trials for two years. A split plot design with two factors was adopted, with five nitrogen rates (0, 75, 150, 225 and 300 kg N·hm-2) as main plots, and two rates of biochar (0 and 7.5 t·hm-2) as submain plots. We collected soil samples at 0-15 cm depth after two years of winter wheat-summer maize rotation and measured physical, chemical, and biological properties. The minimum data set (MDS) was established by using principal component analysis and correlation analysis to analyze the responses of soil quality to nitrogen fertilizer and biochar addition. The results showed that the combined application of nitrogen fertilizer and biochar could improve soil physical properties, increase macroaggregate content, reduce soil bulk density, and increase soil porosity. Both fertilizer application and biochar application had a significant effect on soil microbial biomass carbon and nitrogen. The application of biochar could improve soil urease activity and the contents of soil nutrients and organic carbon. Six out of 16 indicators (urease, microbial biomass carbon, total phosphorous, total nitrogen, pH, and available potassium) relating to soil quality were used to construct MDS, and soil quality index (SQI) was calculated. The variation range of SQI was 0.14-0.87, with that of 225 and 300 kg N·hm-2 nitrogen application combined with biochar application being significantly higher than other treatments. Soil quality could be significantly improved by application of nitrogen fertilizer and biochar. Interactive effect was observed, which was particularly stronger under high nitrogen application rate.


Assuntos
Fertilizantes , Solo , Solo/química , Fertilizantes/análise , Triticum , Zea mays , Nitrogênio/análise , Urease , Carvão Vegetal/química , Carbono , Agricultura/métodos
20.
Front Oncol ; 13: 1128636, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37182167

RESUMO

Objective: To retrospectively analyze the reasons for misdiagnosis of haematolymphoid neoplasms and provide experience for improving the diagnostic level in China. Methods: A retrospective analysis was performed on 2291 cases of haematolymphoid diseases evaluated by the Department of Pathology of our hospital from 1 July 2019 to 30 June 2021. All 2291 cases were reviewed by two hematopathologist experts and classified according to the 2017 revised WHO classification criteria, supplemented immunohistochemistry (IHC), molecular biology and genetic information as needed. The diagnostic discordance between primary and expert review was evaluated. The possible causes of the diagnostic discrepancies were analyzed for each step involved in the procedure of diagnosis. Results: In total, 912 cases did not conform to the expert diagnoses among all the 2291 cases, with a total misdiagnosis rate of 39.8%. Among them, misdiagnosis between benign and malignant lesions accounted for 24.3% (222/912), misdiagnosis between haematolymphoid neoplasms and non-haematolymphoid neoplasms accounted for 3.3% (30/912), misdiagnosis among lineages accounted for 9.3% (85/912), misclassification in lymphoma subtypes accounted for 60.8% (554/912), and other misdiagnoses among benign lesions accounted for 2.3% (21/912) of cases, among which misclassification of lymphoma subtypes was the most common. Conclusion: The accurate diagnosis of haematolymphoid neoplasms is challenging, involving various types of misdiagnosis and complicated causes, however, it is important for precise treatment. Through this analysis, we aimed to highlight the importance of accurate diagnosis, avoid diagnostic pitfalls and to improve the diagnostic level in our country.

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