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1.
Nat Methods ; 21(6): 1103-1113, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38532015

RESUMO

Cell segmentation is a critical step for quantitative single-cell analysis in microscopy images. Existing cell segmentation methods are often tailored to specific modalities or require manual interventions to specify hyper-parameters in different experimental settings. Here, we present a multimodality cell segmentation benchmark, comprising more than 1,500 labeled images derived from more than 50 diverse biological experiments. The top participants developed a Transformer-based deep-learning algorithm that not only exceeds existing methods but can also be applied to diverse microscopy images across imaging platforms and tissue types without manual parameter adjustments. This benchmark and the improved algorithm offer promising avenues for more accurate and versatile cell analysis in microscopy imaging.


Assuntos
Algoritmos , Aprendizado Profundo , Processamento de Imagem Assistida por Computador , Análise de Célula Única , Análise de Célula Única/métodos , Processamento de Imagem Assistida por Computador/métodos , Humanos , Microscopia/métodos , Animais
2.
Proc Natl Acad Sci U S A ; 119(39): e2202157119, 2022 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-36122209

RESUMO

CTNNB1, encoding ß-catenin protein, is the most frequently altered proto-oncogene in hepatic neoplasms. In this study, we studied the significance and pathological mechanism of CTNNB1 gain-of-function mutations in hepatocarcinogenesis. Activated ß-catenin not only triggered hepatic tumorigenesis but also exacerbated Tp53 deletion or hepatitis B virus infection-mediated liver cancer development in mouse models. Using untargeted metabolomic profiling, we identified boosted de novo pyrimidine synthesis as the major metabolic aberration in ß-catenin mutant cell lines and livers. Oncogenic ß-catenin transcriptionally stimulated AKT2, which then phosphorylated the rate-limiting de novo pyrimidine synthesis enzyme CAD (carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, dihydroorotase) on S1406 and S1859 to potentiate nucleotide synthesis. Moreover, inhibition of ß-catenin/AKT2-stimulated pyrimidine synthesis axis preferentially repressed ß-catenin mutant cell proliferation and tumor formation. Therefore, ß-catenin active mutations are oncogenic in various preclinical liver cancer models. Stimulation of ß-catenin/AKT2/CAD signaling cascade on pyrimidine synthesis is an essential and druggable vulnerability for ß-catenin mutant liver cancer.


Assuntos
Neoplasias Hepáticas , Pirimidinas , beta Catenina , Animais , Ácido Aspártico , Carcinogênese , Di-Hidro-Orotase/genética , Di-Hidro-Orotase/metabolismo , Sistemas de Liberação de Medicamentos , Ligases , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/fisiopatologia , Camundongos , Nucleotídeos , Fosfatos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pirimidinas/biossíntese , beta Catenina/metabolismo
3.
Biochem Biophys Res Commun ; 663: 104-112, 2023 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-37121120

RESUMO

HB (hepatoblastoma) is most common in children with liver cancer and few options for treating HB. Thus, it is of great significance to investigate the regulatory mechanism of HB and/or identify new therapeutic targets for clinical treatment of HB. Here, we showed that ACLY (ATP citrate lyase), an important lipometabolic enzyme for de novo biosynthesis of fatty acids and steroids, has a higher expression in HB tissues than noncancerous tissues, and is required for HB cell proliferation. Moreover, knocking down ACLY in HB cells caused severe S-phase arrest and apoptosis. Mechanistically, ACLY knockdown significantly silenced the Wnt signaling pathway and reduced ß-catenin expression in HB cells. Conversely, the apoptotic alleviation of HB cells by overexpressing ACLY was blocked by silencing ß-catenin, suggesting the modulation of HB cells by ACLY-ß-catenin axis. Our results uncovered the role of ACLY in HB cells and presented a theoretical approach for HB targeted therapy in the future.


Assuntos
Hepatoblastoma , Neoplasias Hepáticas , Criança , Humanos , Hepatoblastoma/genética , beta Catenina/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , ATP Citrato (pro-S)-Liase/metabolismo
4.
BMC Pediatr ; 23(1): 235, 2023 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-37173710

RESUMO

BACKGROUND: The study aims to investigate the clinical characteristics of early postnatal period in children with prenatal hydronephrosis (HN) in our single center for 8 years. STUDY DESIGN: The clinical data of 1137 children with prenatal HN from 2012 to 2020 were retrospectively analyzed in our center. Variables of our study mainly included different malformations and urinary tract dilation (UTD) classification, and main outcomes were recurrent hospitalization, urinary tract infection (UTI), jaundice, and surgery. RESULTS: Among the 1137 children with prenatal HN in our center, 188 cases (16.5%) were followed-up in early postnatal period, and 110 cases (58.5%) were found malformations. The incidence of recurrent hospitalization (29.8%) and UTI (72.5%) were higher in malformation, but the incidence of jaundice (46.2%) was higher in non-malformation(P < 0.001). Furthermore, UTI and jaundice were higher in vesicoureteral reflux (VUR) than those in uretero-pelvic junction obstruction (UPJO) (P < 0.05). Meanwhile, Children with UTD P2 and UTD P3 were prone to recurrent UTI, but UTD P0 was prone to jaundice (P < 0.001). In addition, 30 cases (16.0%) of surgery were all with malformations, and the surgical rates of UTD P2 and UTD P3 were higher than those of UTD P0 and UTD P1 (P < 0.001). Lastly, we concluded that the first follow-up should be less than 7 days, the first assessment should be 2 months, and the follow up should be at least once every 3 months. CONCLUSION: Children with prenatal HN have been found many malformations in early postnatal period, and with high-grade UTD were more prone to recurrent UTI, even to surgery. So, prenatal HN with malformations and high-grade UTD should be followed up in early postnatal period regularly.


Assuntos
Hidronefrose , Infecções Urinárias , Sistema Urinário , Criança , Gravidez , Feminino , Humanos , Lactente , Estudos Retrospectivos , Hidronefrose/complicações , Hidronefrose/diagnóstico por imagem , Infecções Urinárias/complicações , Infecções Urinárias/epidemiologia , Dilatação Patológica
5.
Heart Lung Circ ; 32(9): 1080-1088, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37355431

RESUMO

OBJECTIVES: This study examined the echocardiographic characteristics of patients with pulmonary artery intimal sarcoma (PAIS) and compared the results with those from computed tomographic pulmonary angiography (CTPA). METHOD: Twenty-six (26) patients were diagnosed with PAIS at the current institution during the study period, and 23 were eligible for analysis. Echocardiography and CTPA examinations were performed in all enrolled patients. RESULTS: The echocardiography results showed that most lesions had expansive growth in the left pulmonary artery (PA); the right PA; or a combination of the left PA, right PA, and main PA, with extension to the pulmonary valve and/or right ventricular outflow tract. These lesions also had distinctive sieve-like echogenic signals. Echocardiography also showed that some lesions had lobulated shapes, were nearly round and echolucent or with calcifications, and moved during imaging. The lesion distribution was similar in CTPA and echocardiography (p=0.361), but CTPA was more sensitive in detection of the complete shape (p=0.023). CONCLUSIONS: The unique echocardiographic characteristics of PAIS, especially the "sieve sign", could help in the diagnosis of this cancer. Transthoracic echocardiography is a non-invasive technique that appears effective in detecting PAIS.


Assuntos
Neoplasias Pulmonares , Embolia Pulmonar , Sarcoma , Humanos , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/patologia , Pulmão , Sarcoma/diagnóstico por imagem , Ecocardiografia/métodos , Embolia Pulmonar/diagnóstico
6.
Angew Chem Int Ed Engl ; 62(51): e202312638, 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-37759361

RESUMO

Although a variety of dynamic covalent bonds have been successfully used in the development of diverse sustainable thermosetting polymers and their composites, solving the trade-off between recovery efficiency and comprehensive properties is still a major challenge. Herein, a "one-stone-two-birds" strategy of lower rotational energy barrier (Er ) phosphate-derived Diels-Alder (DA) cycloadditions was proposed for easily recyclable carbon fiber (CF)-reinforced epoxy resins (EPs) composites. In such a strategy, the phosphate spacer with lower Er accelerated the segmental mobility and dynamic DA exchange reaction for network rearrangement to achieve high-efficiency repairing, reprocessing of the EPs matrix and its composites and rapid nondestructive recycling of CF; meanwhile, incorporating phosphorus-based units especially reduced their fire hazards. The resulting materials simultaneously showed excellent thermal/mechanical properties, superb fire safety and facile recyclability, realizing the concept of recycling for high-performance thermosetting polymers and composites. This strategy is of great significance for understanding and enriching the molecular connotation of DA chemistry, making it potentially applicable to the design and development of a wide range of dynamic covalent adaptable materials toward practical cutting-edge-tech applications.

7.
Opt Express ; 30(24): 43741-43751, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36523066

RESUMO

In the paper, a type of phase change metamaterial for tunable infrared stealth and camouflage is proposed and numerically studied. The metamaterial combines high temperature resistant metal Mo with phase-changing material GST and can be switched between the infrared "stealthy" and "non-stealthy" states through the phase change process of the GST. At the amorphous state of GST, there is a high absorption peak at the atmospheric absorption spectral range, which can achieve infrared stealth in the atmospheric window together with good radiative heat dissipation in the non-atmospheric window. While at the crystalline state of GST, the absorption peak becomes broader and exhibits high absorption in the long-wave infrared atmospheric window, leading to a "non-stealthy" state. The relationship between the infrared stealth performance of the structure with the polarization and incident angle of the incident light is also studied in detail. The proposed infrared stealth metamaterial employs a simple multilayer structure and could be fabricated in large scale. Our work will promote the research of dynamically tunable, large scale phase change metamaterials for infrared stealth as well as energy and other applications.

8.
Heart Lung Circ ; 31(2): 230-238, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34417115

RESUMO

OBJECTIVES: A retrospective cohort study was designed to describe the clinical features and outcomes of pulmonary artery sarcoma (PAS). METHODS: Twenty-two (22) consecutive patients diagnosed with PAS by pathological examination were enrolled and followed up until they died or until January 2020. The medical records were retrospectively reviewed to evaluate the clinical characteristics, image findings, and outcomes. RESULTS: 1) Twenty-one (21, 95.5%) patients were firstly misdiagnosed. Dyspnoea was the most common presenting symptom (19 of 22, 86.4%). 2) Filling defects in the right pulmonary artery were seen in 17 patients (77.3%) with computed tomography pulmonary angiography or magnetic resonance pulmonary angiography. Among those patients, 14 underwent positron emission tomography-computed tomography detection and 13 (92.9%) were found to have increased uptake value in the pulmonary artery. 3) The median survival (from diagnosis to death or January 2020) of the total series was 11.6 months (range, 0.7-68.5 months). The estimated cumulative survival rates at 1, 2, and 3 years were 52.6%, 32.8%, and 19.7%, respectively. Patients who received surgery and/or chemo-radiotherapy treatment had a better survival rate compared with patients without treatment (the estimated cumulative survival rates at 1, 2, and 3 years were 60.3%, 39.1%, and 29.3%, respectively, vs 33.3%, 16.6%, and 0, accordingly) and better survival time (median survival 17.02 vs 3.16 months, respectively) (p=0.025). CONCLUSIONS: Pulmonary artery sarcoma is easily misdiagnosed, as the symptoms and routine image detection are nonspecific. Positron emission tomography-computed tomography may be helpful in diagnosis. Surgery and/or chemo-radiotherapy offer a chance for better outcomes.


Assuntos
Neoplasias Pulmonares , Embolia Pulmonar , Sarcoma , Neoplasias Vasculares , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Artéria Pulmonar/diagnóstico por imagem , Estudos Retrospectivos , Sarcoma/diagnóstico , Sarcoma/terapia , Tomografia Computadorizada por Raios X , Neoplasias Vasculares/diagnóstico , Neoplasias Vasculares/terapia
9.
J Thromb Thrombolysis ; 51(3): 703-710, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32894400

RESUMO

A definitive diagnosis of heparin-induced thrombocytopenia (HIT) is difficult to make, especially in patients undergoing cardiac surgery. In this retrospective cohort study, we assessed the platelet count trends and the response to fondaparinux in a population of patients of suspected HIT after pulmonary endarterectomy (PEA). Patients enrolled in this study were over the age of 18 years, and survived longer than 7 days after PEA between January 1, 2011 and December 31, 2015. HIT likelihood was assessed by the 4 T's score and interpreted by our institutional algorithm. 54 patients were operated, and 49 patients met the inclusion criteria. Six patients met the criteria for suspected HIT and were treated with fondaparinux until the platelet recovered. No significant difference was observed of clinical characteristics between intermediate to high HIT likelihood patients (HIT SUSPECTED) and low HIT likelihood patients (NO HIT SUSPECTED). HIT SUSPECTED patients reached platelet count lowest later (about 5.5 days after PEA), while NO HIT SUSPECTED patients is about 4.0 days after PEA. Percentage of platelet counts decrease (> 50%) was larger than NO HIT SUSPECTED patients (< 50%). There was no difference in mortality or residual pulmonary hypertension between HIT SUSPECTED and NO HIT SUSPECTED patients. Two HIT SUSPECTED patients who used heparin after PEA died, the other four survived by replacing heparin or low molecular weight heparin with fondaparinux. Suspected HIT patients should be surveilled carefully. Platelet counts trends may have some hints in the prevention of HIT. Fondaparinux may be effective for patients with suspected HIT.


Assuntos
Endarterectomia/efeitos adversos , Fondaparinux/administração & dosagem , Heparina/efeitos adversos , Hipertensão Pulmonar , Contagem de Plaquetas , Complicações Pós-Operatórias , Trombocitopenia , Adulto , China/epidemiologia , Estudos de Coortes , Endarterectomia/métodos , Inibidores do Fator Xa/administração & dosagem , Feminino , Heparina/administração & dosagem , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/prevenção & controle , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas/métodos , Contagem de Plaquetas/estatística & dados numéricos , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/prevenção & controle , Embolia Pulmonar/complicações , Embolia Pulmonar/mortalidade , Embolia Pulmonar/cirurgia , Risco Ajustado/métodos , Trombocitopenia/sangue , Trombocitopenia/induzido quimicamente , Trombocitopenia/diagnóstico , Trombocitopenia/epidemiologia
10.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 38(6): 1062-1071, 2021 Dec 25.
Artigo em Zh | MEDLINE | ID: mdl-34970888

RESUMO

Glioma is the most common malignant brain tumor and classification of low grade glioma (LGG) and high grade glioma (HGG) is an important reference of making decisions on patient treatment options and prognosis. This work is largely done manually by pathologist based on an examination of whole slide image (WSI), which is arduous and heavily dependent on doctors' experience. In the World Health Organization (WHO) criteria, grade of glioma is closely related to hypercellularity, nuclear atypia and necrosis. Inspired by this, this paper designed and extracted cell density and atypia features to classify LGG and HGG. First, regions of interest (ROI) were located by analyzing cell density and global density features were extracted as well. Second, local density and atypia features were extracted in ROI. Third, balanced support vector machine (SVM) classifier was trained and tested using 10 selected features. The area under the curve (AUC) and accuracy (ACC) of 5-fold cross validation were 0.92 ± 0.01 and 0.82 ± 0.01 respectively. The results demonstrate that the proposed method of locating ROI is effective and the designed features of density and atypia can be used to predict glioma grade accurately, which can provide reliable basis for clinical diagnosis.


Assuntos
Neoplasias Encefálicas , Glioma , Neoplasias Encefálicas/diagnóstico por imagem , Glioma/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Gradação de Tumores , Máquina de Vetores de Suporte
11.
Mol Cancer ; 19(1): 24, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32019547

RESUMO

After the publication of this work [1], the authors noticed that the affiliations were incorrectly provided. Updated affiliation section is provided in this paper.

12.
Cancer Immunol Immunother ; 69(11): 2333-2343, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32514618

RESUMO

Patients with pediatric cancers such as neuroblastoma (NB) are often unresponsive to checkpoint blockade immunotherapy. One major factor in pediatric tumor resistance to immunotherapy is considered to be the low mutation rate of pediatric tumors. Another factor may be the overexpression of additional inhibitory pathways. While analyzing the RNA-sequencing database TARGET, we found that human NB tumors overexpress immune checkpoint molecule CD200. To determine its significance and impact on tumor immune microenvironment, we analyzed 49 cases of previously untreated, surgically removed NB tumors using immunohistochemistry and multi-color flow cytometry (FACS). We found that CD200 is overexpressed in more than 90% of NB tumors. In the tumor microenvironment of NB, CD200 is mainly overexpressed in CD45- NB tumor cells, while its cognate receptor (CD200R) is mainly expressed in HLA-DR+CD14+ myeloid cells and CD11c+ dendritic cells. Low-level expression of CD200R is also observed in tumor-infiltrating CD4+ and CD8+ T cells. In NB tumors with higher CD200 expression (CD200high), we observed lower numbers of HLA-DR+CD14+ myeloid cells and less tumor-infiltrating CD4+ and CD8+ T cells. Moreover, we found that CD4+ and CD8+ T cells produced less IFN-γ and/or TNF-α in CD200high NB tumors. Thus, CD200-CD200R pathway appears to downregulate anti-tumor immunity in the tumor microenvironment of NB tumors, and blockade of this pathway may be beneficial for NB patients.


Assuntos
Antígenos CD/imunologia , Linfócitos do Interstício Tumoral/imunologia , Neuroblastoma/imunologia , Microambiente Tumoral/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Receptores de Orexina/imunologia , Evasão Tumoral/imunologia
13.
Pediatr Blood Cancer ; 67(3): e28108, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31782614

RESUMO

BACKGROUND: Neuroblastoma (NB) is a deadly solid tumor of children. Krüppel-like factor 9 (KLF9) has prodifferentiation and tumor suppression functions in several types of cancers. Here, we aimed to investigate the effects of KLF9 on NB differentiation and growth and to elucidate the underlying mechanism. PROCEDURE: Sixty-five NB paraffin samples were assessed for expression levels of KLF9 and sonic hedgehog (SHH) signaling pathway proteins by immunohistochemistry. The associations between expression of KLF9 and the SHH pathway components and patients' clinicopathologic characteristics were estimated. The impacts of KLF9 on cell differentiation, proliferation, and invasion were investigated in two NB cell lines (SH-SY5Y and IMR32). Additionally, chromatin immunoprecipitation (ChIP) and luciferase reporter assays were used to elucidate the mechanism by which KLF9 regulates SHH signaling. RESULTS: Differentiating NB specimens showed significantly higher KLF9 expression levels than undifferentiated/poorly differentiated ones. Moreover, increased KLF9 expression was associated with favorable prognoses in patients with NB. A negative correlation was found between KLF9 and SHH signaling expression levels in NB specimens. In vitro assays revealed that KLF9 promoted the differentiation of NB cells and inhibited their proliferation and invasion via suppression of the SHH pathway. Furthermore, KLF9 binding sites in the SHH promoter were identified by ChIP and luciferase reporter assays. CONCLUSIONS: KLF9 exerts prodifferentiation and growth-inhibition effects on NB via suppression of the SHH pathway, suggesting a potential role of KLF9 in NB therapy.


Assuntos
Biomarcadores Tumorais/metabolismo , Diferenciação Celular , Regulação Neoplásica da Expressão Gênica , Proteínas Hedgehog/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Neuroblastoma/patologia , Apoptose , Biomarcadores Tumorais/genética , Proliferação de Células , Seguimentos , Proteínas Hedgehog/genética , Humanos , Fatores de Transcrição Kruppel-Like/genética , Invasividade Neoplásica , Neuroblastoma/genética , Neuroblastoma/metabolismo , Prognóstico , Regiões Promotoras Genéticas , Células Tumorais Cultivadas
14.
Inorg Chem ; 59(4): 2406-2412, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32030979

RESUMO

Transition-metal sulfide is a good kind of material for supercapacitors because of the large capacity. Nevertheless, the low electroconductivity, slow reaction kinetics, and limited active centers lead to poor electrochemical properties such as long-term cycling stability. In the present work, nano nickel metal-organic framework (Ni-MOF) was constructed by using the nitrogen-rich functional group ligand 2,4,6-tris(3,5-dicarboxylphenylamino)-1,3,5-triazin and compounded with carbon nanotubes (CNTs) to prepare Ni-MOF/CNTs composite, which was used as a precursor to prepare the MOFs-derived NC/Ni-Ni3S4/CNTs composite with the Ni3S4 uniformly distributed in the three-dimensional (3D) conductive network. The rich nitrogen doping and 3D conductive network constructed by CNTs improved the conductivity, prompted the rapid entry of electrolyte, and improved the reaction kinetics of NC/Ni-Ni3S4/CNTs, thus obtained excellent specific capacitance, coulomb efficiency, and cyclic stability. The specific capacitance of NC/Ni-Ni3S4/CNTs is 1489.9 F/g at 1 A/g, which remains 800 F/g at 10 A/g, showing good rate performance.

15.
Ann Hepatol ; 19(5): 530-534, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32532590

RESUMO

INTRODUCTION AND OBJECTIVES: Infantile hepatic hemangioendothelioma (IHHE) is a benign liver tumor, associated with hypothyroidism and vascular malformations along the skin, brain, digestive tract and other organs. Here, we determined a single-center patient cohort by evaluating the effectiveness and safety of propranolol and sirolimus for the treatment of IHHE. PATIENTS AND METHODS: We performed a monocentric and observational study, based on clinical data obtained from 20 cases of IHHE treated with oral propranolol and sirolimus at the Shanghai Children's Medical Center (SCMC), between December 2017 and April 2019. All cases were confirmed by abdominal enhanced CT examination (18/20, 90%) and sustained decrease of alpha fetoprotein (AFP) (2/20, 10%). Propranolol treatment was standardized as once a day at 1.0mg/kg for patients younger than 2 months, and twice a day at 1.0mg/kg (per dose) for patients older than 2 months. Sirolimus was used to treat refractory IHHE patients after 6 months of propranolol treatment, and initial dosing was at 0.8mg/m2 body surface per dose, administered every 12h. Upon treatment, abdominal ultrasound scanning was regularly performed to evaluate any therapeutic effects. All children were followed up for 6-22 months (mean value of 12.75 months). The clinical manifestations and therapeutic effects, including complications during drug management, were reviewed after periodic follow-up. RESULTS: The effective rate of propranolol for the treatment of children with IHHE was 85% (17/20). In most cases, the AFP levels gradually decreased into the normal range. A complete response (CR) was achieved in 3 cases, partial response (PR) for 14 cases, progressive disease (PD) for 2 cases and stable disease (SD) was only detected once. Lesions decreased in two PD patients after administration of oral sirolimus. No serious adverse reactions were observed. CONCLUSION: This study indicates that both propranolol and sirolimus were effective drugs for the treatment of children with IHHE at SCMC.


Assuntos
Antineoplásicos/administração & dosagem , Hemangioendotelioma/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Propranolol/administração & dosagem , Sirolimo/administração & dosagem , Administração Oral , Antineoplásicos/efeitos adversos , Pré-Escolar , China , Feminino , Hemangioendotelioma/sangue , Hemangioendotelioma/diagnóstico por imagem , Hemangioendotelioma/patologia , Humanos , Lactente , Recém-Nascido , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Masculino , Propranolol/efeitos adversos , Sirolimo/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , alfa-Fetoproteínas/metabolismo
16.
BMC Musculoskelet Disord ; 21(1): 577, 2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32843029

RESUMO

BACKGROUND: Gorham-Stout disease (GSD) is a rare disease characterized by bone lesions and osteolysis. Therapy usually involves surgical resection. Sirolimus (Rapamycin) is used in some patients with GSD but the efficacy and safety of Sirolimus remains unclear. We propose that Sirolimus may be a novel therapeutic for GSD and present a case and review of literature that supports this. CASE PRESENTATION: We presented a 1-year-old boy with GSD involving osteolysis of the right humerus with fracture of the left femur complicated by an effusion in the right pleural cavity. X-rays showed osteolysis in the right clavicle. A large pleural effusion was observed on the right-side, and the left lung was significantly compressed. X-rays also showed a fracture of the left femur. A femoral biopsy was performed that showed necrotic tissue in the cortical bone and a large number of irregularly shaped capillaries that proliferated within the necrotic tissue. Dilated lymphatic vessels were seen adjacent to the cortex, with fibrous tissue hyperplasia. We prescribed sirolimus, which is an oral mTOR inhibitor, for two consecutive years. The boy recovered well without other progressive bone lesions and participates in normal daily activities. His growth and development are the same as that of his peers. DISCUSSION AND CONCLUSION: Gorham-Stout disease is a rare and enigmatic disease characterized by the presentation of an intraosseous lymphatic anomaly (LM), which results in progressive bone resorption. Based on this case report and a literature review, we conclude that sirolimus may be an effective alternative medication for GSD.


Assuntos
Osteólise Essencial , Osteólise , Osso e Ossos , Humanos , Lactente , Masculino , Osteólise Essencial/diagnóstico por imagem , Osteólise Essencial/tratamento farmacológico , Radiografia , Sirolimo/uso terapêutico
17.
Mol Cancer ; 18(1): 188, 2019 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-31870368

RESUMO

BACKGROUND: N6-Methyladenosine (m6A) modification has been implicated in many biological processes. It is important for the regulation of messenger RNA (mRNA) stability, splicing, and translation. However, its role in cancer has not been studied in detail. Here we investigated the biological role and underlying mechanism of m6A modification in hepatoblastoma (HB). METHODS: We used Reverse transcription quantitative real-time PCR (RT-qPCR) and Western blotting to determine the expression of m6A related factors. And we clarified the effects of these factors on HB cells using cell proliferation assay, colony formation, apoptotic assay. Then we investigated of methyltransferase-like 13 (METTL3) and its correlation with clinicopathological features and used xenograft experiment to check METTL3 effect in vivo. m6A-Seq was used to profiled m6A transcriptome-wide in hepatoblastoma tumor tissue and normal tissue. Finally, methylated RNA immunoprecipitation (MeRIP) assay, RNA remaining assay to perform the regulator mechanism of MEETL3 on the target CTNNB1 in HB. RESULTS: In this research, we discovered that m6A modifications are increased in hepatoblastoma, and METTL3 is the main factor involved with aberrant m6A modification. We also profiled m6A across the whole transcriptome in hepatoblastoma tumor tissues and normal tissues. Our findings suggest that m6A is highly expressed in hepatoblastoma tumors. Also, m6A is enriched not only around the stop codon, but also around the coding sequence (CDS) region. Gene ontology analysis indicates that m6A mRNA methylation contributes significantly to regulate the Wnt/ß-catenin pathway. Reduced m6A methylation can lead to a decrease in expression and stability of the CTNNB1. CONCLUSION: Overall our findings suggest enhanced m6A mRNA methylation as an oncogenic mechanism in hepatoblastoma, METTL3 is significantly up-regulated in HB and promotes HB development. And identify CTNNB1 as a regulator of METTL3 guided m6A modification in HB.

18.
Soft Matter ; 15(19): 3897-3905, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30993273

RESUMO

Currently, robust and functional hydrogels have attracted extensive attention due to their potential applications in wastewater treatment, farmland water conservation and other fields. Herein, a series of hydrophobic association hydrogels assisted by titanium dioxide (TiO2) was fabricated via one-pot in situ photo-induced polymerization. TiO2 nanoparticles could act as both photo-initiators and physical crosslinking points. The TiO2-assisted hydrophobic association hydrogels exhibited a high tensile strength of 306 kPa, superior compression strength of 2.17 MPa and excellent fatigue resistance. Simultaneously, the incorporation of TiO2 endowed the hydrogel with photocatalytic capacity for dye wastewater treatment based on the inherent nature of TiO2. The results indicated that the hydrogels contributed to the degradation of various ionic dyes including methylene blue, rhodamine B and bromophenol blue, and the removal of methylene blue achieved a rate of 96.63%. Significantly, the hydrogel could be repeatedly utilized and the removal rate showed no evident decrease after five cycles, indicating that the hydrogels could be powerful candidates as photocatalysts for dye wastewater treatment.

19.
Mar Drugs ; 17(5)2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31052268

RESUMO

Prorocentrum lima is a typical benthic toxic dinoflagellate, which can produce phycotoxins such as okadaic acid (OA). In this study, we identified three ABC transporter genes (ABCB1, ABCC1 and ABCG2) and characterized their expression patterns, as well as OA production under different environmental conditions in P. lima. We found that the three ABC transporters all showed high identity with related ABC proteins from other species, and contained classical features of ABC transport proteins. Among them, ABCG2 was a half size transporter. The three ABC transporter genes displayed various expression profiles under different conditions. The high concentration of Cu2+ could up-regulate ABCB1, ABCC1 and ABCG2 transcripts in P. lima, suggesting the potential defensive role of ABC transporters against metal ions in surrounding waters. Cu2+, in some concentration, could induce OA production; meanwhile, tributyltin inhibited OA accumulation. The grazer Artemia salina could induce OA production, and P. lima displayed some toxicity to the grazer, indicating the possibility of OA as an anti-grazing chemical. Collectively, our results revealed intriguing data about OA production and the expression patterns of three ABC transporter genes. However, we could not find any significant correlation between OA production and expression pattern of the three ABC transporters in P. lima. Our results might provide new molecular insights on the defensive responses of P. lima to the surrounding environment.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Dinoflagellida/metabolismo , Dinoflagellida/crescimento & desenvolvimento , Meio Ambiente , Toxinas Marinhas/química , Ácido Okadáico/metabolismo , RNA Mensageiro
20.
Sensors (Basel) ; 19(4)2019 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-30781582

RESUMO

In order to resolve the large fluctuations in temperature range problem of Luojia 1-01 satellite caused by low heat inertia and poor thermal conductivity of structure, a quasi-all-passive thermal control system (TCS) design is presented under the conditions of limited resources including mass and power consumption. The effectiveness of the TCS design is verified by both ground thermal balanced test and related telemetry data of on-orbit performance. Firstly, according to the structural features and working modes of the satellite, isothermal design was implemented and the effectiveness was verified by thermal analysis using finite element method. Secondly, based on the results of the thermal analysis, thermal design was optimized and verified by the thermal balanced test. Finally, the thermal design was proved to be effective by temperature data acquired from telemetry data of on-orbit performance, and the thermal analysis model was improved and updated based on the results of thermal balanced test and temperature data of on-orbit performance. The on-orbit data indicates that temperature of optical camera stables at about 12 °C, temperature of battery stables at 19 °C, temperature of instruments inside and outside the satellite cabin is ranging from 10 °C to 25 °C. Temperature fluctuation range of optical camera is less than 2 °C when it is not imaging. Temperature fluctuation range of instruments not facing the sun is less than 4 °C. The data suggests that the temperature level of the satellite meets general design requirements, and the quasi-all-passive TCS design of the satellite is practicable.

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