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OBJECTIVE: To describe the ultrasound characteristics of nodular localized cutaneous neurofibroma (NLCN). MATERIALS AND METHODS: Clinical features and ultrasound characteristics of 43 lesions of 40 patients pathologically proven as NLCNs at Peking University Shenzhen Hospital from October 2014 to May 2022 were analyzed retrospectively. The location, length-to-thickness (L/T) ratio, thickness-to-width (T/W) ratio, shape, margin, capsule, echogenicity, echotexture, posterior features, vascularity, and "rat tail sign" were evaluated. RESULTS: All ultrasound findings showed almost perfect agreement. More than a half of NLCNs (n = 24, 55.8%, p < 0.001) were located in the subcutaneous fat layer wholly with well-demarcation from dermis and deep fascia. Most of the NLCNs were fusiform shape (n = 27, 62.8%, p < 0.001) in the long axis and oval shape (n = 35, 81.4%, p < 0.001) in the short axis. The other ultrasound findings of NLCNs included well-defined (n = 42, 97.7%, p < 0.001), encapsulated (n = 39, 90.7%, p < 0.001), predominately hypoechoic (n = 34, 79.1%, p < 0.001), homogeneous (n = 39, 90.7%, p < 0.001), posterior enhancement (n = 29, 67.4%, p = 0.033), and avascularity (n = 37, 86.0%, p < 0.001). Only a quarter (n = 11, 25.6%, p = 0.002) of lesions were recognized with the "rat tail sign." CONCLUSION: NLCNs present as fusiform shape in long axis and round shape in short axis. The common ultrasound findings of NLCNs are well-defined, encapsulated, predominately hypoechoic, homogeneous lesion with posterior enhancement, and poor blood supply. The "rat tail sign" has low sensitivity in NLCNs.
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Neurofibroma , Neoplasias Cutâneas , Ultrassonografia , Humanos , Feminino , Neurofibroma/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Ultrassonografia/métodos , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/patologia , Adulto Jovem , Adolescente , Idoso , Pele/diagnóstico por imagem , Pele/patologia , CriançaRESUMO
OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a well-known complex multicomponent disease characterized by systemic inflammation that frequently coexists with other conditions. We investigated the relationship between some inflammatory markers and complications in COPD patients to explore the possible roles of inflammation in these comorbidities. METHODS: This study used cross-sectional and case-control methods. We included 336 hospitalized COPD patients, 64 healthy controls, and 42 major depression patients and evaluated all participants using the Hamilton Rating Scale. C-reactive protein (CRP), red blood cell distribution width (RDW), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) were collected and measured in the study population. Statistical methods were used to analyze the association of inflammatory markers with COPD comorbidities. RESULTS: Cor pulmonale and psychological comorbidities (depression and anxiety) were more common in this study on COPD patients. We found that MLR (OR = 2.054, 95 % CI 1.129-3.735, p = 0.018) and RDW (OR = 1.367, 95 % CI 1.178-1.586, p = 0.000) were related to COPD patients complicated with cor pulmonale, while IL-6 (OR = 1.026, 95 % CI 1.001-1.053, p = 0.045) and RDW (OR = 1.280, 95 % CI 1.055-1.552, p = 0.012) were related to depression symptoms. CONCLUSION: MLR, RDW and IL-6 were closely related to cor pulmonale and depression in COPD patients. IL-1 ß and IL-6 are closely related to depression in humans.
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Doença Pulmonar Obstrutiva Crônica , Doença Cardiopulmonar , Humanos , Citocinas , Interleucina-6 , Biomarcadores , Estudos Transversais , Linfócitos , Inflamação , Neutrófilos , Estudos RetrospectivosRESUMO
OBJECTIVES: The study was designed to evaluate entheseal sites and anterior chest wall (ACW) of patients with ankylosing spondylitis (AS) using ultrasound (US) and investigate the correlation between disease activity and US score. METHODS: This prospective cross-sectional study included 104 patients with AS and 50 control subjects. Each patient underwent US scanning of 23 entheses and 11 sites of the ACW. The US features, including hypoechogenicity, thickness, erosion, calcification, bursitis, and Doppler signal, were evaluated. Disease activity was assessed based on C reactive protein (CRP), erythrocyte sedimentation rate (ESR), disease activity score-C reactive protein (ASDAS-CRP), and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). RESULTS: The most commonly involved entheses on US were the Achilles tendon (AT) and quadriceps tendon (QT). The most involved site of ACW was the sternoclavicular joint (SCJ). Compared with the control group, significant differences were observed in the AS group in the rates of US enthesitis and ACW in AT (P = .01), SCJ (P = .00), and costochondral joint (CCJ) (P = .01). Patients with high or very high disease activity had a higher erosion score (P = .02). The erosion score was weakly positively associated with CRP, ESR, BASDAI, ASDAS-CRP, and ASDAS-ESR (correlation coefficient: 0.22-0.45). CONCLUSIONS: The most commonly involved entheseal sites on US were AT and QT, while the site of ACW was SCJ. The US assessment of AS should take the ACW into account. High disease activity might indicate erosion in AS.
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BACKGROUND: Nodular fasciitis (NF) has nonspecific clinical manifestations and is often misdiagnosed as sarcoma. The investigations of imaging methods for NF were limited. OBJECTIVE: To analyze the ultrasound (US) features of NF, and to evaluate the diagnostic value of US for NF. MATERIALS AND METHODS: A total of 61 NF patients were recruited retrospectively, and 551 lesions in the subcutaneous fat layer were included for comparison. We evaluated the ultrasound features of the patients and divided the NF cases into three types. Chi-square test or Fisher exact test were conducted to detect the potential difference in the distributions of three types in the two groups. RESULTS: Among the 61 NF cases, 65.6% were in the upper extremities (n = 40). The proportion of type 1, 2, and 3 were 57.4%, 24.6%, and 18.0%, respectively. NF were significantly more likely locating in the upper extremities than the other soft tissue tumors (p < 0.001). Type 1 and type 2 of sonographic features were significantly more commonly observed in NF than other soft tissue tumors among the three types (p < 0.001). CONCLUSION: The type 1 and type 2 of US features can help to distinguish NF from other lesions. US has great potential to improve the diagnostic accuracy and reduce the unnecessary surgery.
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Fasciite , Neoplasias de Tecidos Moles , Humanos , Diagnóstico Diferencial , Estudos Retrospectivos , Fasciite/diagnóstico por imagem , Extremidade Superior , Neoplasias de Tecidos Moles/diagnóstico por imagemRESUMO
Sentinel lymph node biopsy has been regarded as the standard procedure for early staging breast cancer. One of the key steps is to locate the sentinel lymph node (SLN). The recommended method is the joint use of blue dye and radioisotope. However, due to radionuclide radiation and high cost, it is urgent to develop more convenient and sensitive imaging methods to accurately locate SLN. This article discusses the advancement of accurately locating SLN by isotope tracer imaging, magnetic tracer method, computed tomographic lymphography, and trans-lymphatic contrast-enhanced ultrasound, as well as proposing new propose for clinical diagnosis.
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Neoplasias da Mama , Linfonodo Sentinela , Neoplasias da Mama/patologia , Feminino , Humanos , Linfonodos/patologia , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Linfografia/métodos , Estadiamento de Neoplasias , Linfonodo Sentinela/diagnóstico por imagem , Biópsia de Linfonodo Sentinela/métodosRESUMO
We found previously that KLF4 expression was up-regulated in cultured rat and human pulmonary artery smooth muscle cells (PASMCs) exposed to cigarette smoke (CS) extract and in pulmonary artery from rats with pulmonary hypertension induced by CS. Here, we aim to investigate whether CS-induced pulmonary hypertension (PH) is prevented and ameliorated by targeted pulmonary vascular gene knockdown of KLF4 via adeno-associated virus 1 (AAV1)-KLF4-shRNA in vivo in rat model. The preventive and therapeutic effects were observed according to the different time-point of AAV1-KLF4-shRNA intratracheal administration. We tested haemodynamic measurements of systemic and pulmonary circulations and observed the degree of pulmonary vascular remodelling. In the preventive experiment, KLF4 expression and some pulmonary circulation hemodynamic measurements such as right ventricular systolic pressure (RVSP), mean right ventricular pressure (mRVP), peak RV pressure rate of rise (dP/dt max) and right ventricle (RV) contractility index were increased significantly in the CS-induced PH model. While in the prevention group (AAV1-KLF4-shRNA group), RVSP, mRVP, dP/dt max and RV contractility index which are associated with systolic function of right ventricle decreased and the degree of pulmonary vascular remodelling relieved. In the therapeutic experiment, we observed a similar trend. Our findings emphasize the feasibility of sustained pulmonary vascular KLF4 gene knockdown using intratracheal delivery of AAV1 in an animal model of cigarette smoke-induced PH and determined gene transfer of KLF4-shRNA could prevent and ameliorate the progression of PH.
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Dependovirus/metabolismo , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/terapia , Fatores de Transcrição Kruppel-Like/metabolismo , RNA Interferente Pequeno/uso terapêutico , Fumar/efeitos adversos , Animais , Cardiomegalia/patologia , Cardiomegalia/fisiopatologia , Diástole , Proteínas de Fluorescência Verde/metabolismo , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/prevenção & controle , Fator 4 Semelhante a Kruppel , Masculino , Contração Miocárdica , Osteopontina/metabolismo , Fosforilação , Antígeno Nuclear de Célula em Proliferação/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Ratos Sprague-Dawley , Traqueia/patologia , Traqueia/fisiopatologiaRESUMO
BACKGROUND One of the most important factors in the pathogenesis of COPD (chronic obstructive pulmonary disease) is oxidative stress. GGT (gamma-glutamyltransferase) has been regarded as a novel marker of oxidative stress over the last few years. This study aimed to compare the serum levels of GGT during stable and acute exacerbations of COPD at a single center. MATERIAL AND METHODS The research included 117 patients with AECOPD (acute exacerbation of chronic obstructive pulmonary disease), 107 patients with stable COPD, and 112 control subjects. Serum GGT, spirometry function, and other clinical parameters (anthropometric and biochemical measurements) were evaluated and compared among the subjects. RESULTS Serum GGT was elevated in patients with stable COPD in comparison to the control subjects. Its level was inversely related to lung function. It was also significantly higher in AECOPD patients compared to stable COPD patients. We also found that a GGT level of 21.2 IU/L displays a reliable diagnostic prediction of COPD and that a GGT level of 26.5 IU/L can be applied to predict the exacerbation of COPD. CONCLUSIONS Our research demonstrates that serum GGT level is inversely associated with pulmonary function and may serve as a biomarker during the progression of COPD. The monitoring of GGT values can be applied to evaluating COPD and its exacerbation risk.
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Doença Pulmonar Obstrutiva Crônica/sangue , gama-Glutamiltransferase/sangue , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Progressão da Doença , Feminino , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Índice de Gravidade de DoençaRESUMO
Breast cancer ranks first among cancers affecting women's health. Our work aims to realize the intelligence of the medical ultrasound equipment with limited computational capability, which is used for the assistant detection of breast lesions. We embed the high-computational deep learning algorithm into the medical ultrasound equipment with limited computational capability by two techniques: (1) lightweight neural network: considering the limited computational capability of ultrasound equipment, a lightweight neural network is designed, which greatly reduces the amount of calculation. And we use the technique of knowledge distillation to train the low-precision network helped with the high-precision network; (2) asynchronous calculations: consider four frames of ultrasound images as a group; the image of the first frame of each group is used as the input of the network, and the result is respectively fused with the images of the fourth to seventh frames. An amount of computation of 30 GFLO/frame is required for the proposed lightweight neural network, about 1/6 of that of the large high-precision network. After trained from scratch using the knowledge distillation technique, the detection performance of the lightweight neural network (sensitivity = 89.25%, specificity = 96.33%, the average precision [AP] = 0.85) is close to that of the high-precision network (sensitivity = 98.3%, specificity = 88.33%, AP = 0.91). By asynchronous calculation, we achieve real-time automatic detection of 24 fps (frames per second) on the ultrasound equipment. Our work proposes a method to realize the intelligence of the low-computation-power ultrasonic equipment, and successfully achieves the real-time assistant detection of breast lesions. The significance of the study is as follows: (1) The proposed method is of practical significance in assisting doctors to detect breast lesions; (2) our method provides some practical and theoretical support for the development and engineering of intelligent equipment based on artificial intelligence algorithms.
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Inteligência Artificial , Neoplasias da Mama/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/instrumentação , Interpretação de Imagem Assistida por Computador/métodos , Ultrassonografia Mamária/métodos , Pequim , Mama/diagnóstico por imagem , Bases de Dados Factuais , Feminino , HumanosRESUMO
BACKGROUND: Sentinel lymph node (SLN) property assessment (with or without metastasis) is important when deciding the surgery for breast cancer; however, the current diagnosis of SLN metastasis remains to be studied. microRNAs (miRNAs) have been confirmed previously as a molecular marker for the diagnosis, development and prognosis of tumors. However, the detailed role of miRNAs in the diagnosis of SLN metastasis has not been reported. METHODS: The present study aimed to explore the potential use of miRNAs in the diagnosis of SLN using RNA sequencing (RNA-seq) and a quantitative real-time polymerase chain reaction (qRT-PCR) to compare the expression profiles of miRNAs in patients with breast cancer with or without SLN metastasis. RESULTS: The RNA-seq results revealed that 1993 miRNAs were differentially expressed in patients with breast cancer with SLN metastasis. Among these miRNAs, 1960 were up-regulated and 33 were down-regulated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed that these differentially expressed miRNAs were associated with tumor growth and metastasis and were also predicted to regulate a series of tumorigenesis and metastasis genes. In particular, the most differentially expressed miRNAs were validated by qRT-PCR, such that miR-200a-3p and miR-96-5p were up-regulated and miR-1-3p and miR-486-3p were down-regulated in patients with breast cancer with SLN metastasis. CONCLUSIONS: The findings of the present study suggest that there is an association of miRNAs with SLN metastasis and also that miRNAs function as biomarkers with respect to the choice of therapy and disease prognosis.
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Neoplasias da Mama/genética , MicroRNAs/genética , Linfonodo Sentinela/metabolismo , Adulto , Biomarcadores Tumorais/genética , Neoplasias da Mama/patologia , Feminino , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Metástase Linfática/genética , Metástase Linfática/patologia , Pessoa de Meia-Idade , Prognóstico , Análise de Sequência de RNA/métodos , Sequenciamento do Exoma/métodos , Adulto JovemRESUMO
OBJECTIVES: To explore the best individualized systematic prostate biopsy method. METHODS: We retrospectively analyzed the clinical data of 1211 patients who underwent 12-core systematic prostate biopsy guided by transrectal ultrasound from January 2011 to March 2018. Other biopsy core methods (6-, 8-, and 10-core) were estimated from the 12-core biopsy that was performed. Differences in the detection rates of prostate cancer (PCa) and clinically significant prostate cancer (csPCa) were compared. RESULTS: A total of 498 cases of PCa (41.1%) were detected, and 423 cases (34.9%) were csPCa. There was no significant difference between the 12- and 10-core prostate biopsy strategies in the total detection rates of PCa and csPCa (P > .05). In the subgroup of patients with a maximal prostate cross-sectional area of less than 15 cm2 , there was a significant difference between the 12-core method and the standard 6-core method (P = .03) but no significant differences between the other methods in the detection rate of PCa (P > .05), but in the detection rate of csPCa, the 12-core method differed significantly from the other methods (P = .02-.04) except for the 10-core method (P > .05). In patients with a prostate-specific antigen concentration of 20 ng/mL or higher, there were no significant differences between the 12-core method and all of the other methods (P > 0.05). In patients younger than 70 years and 70 years or older, the 12-core method differed significantly from the other methods (P < .01-.03) except for the 10-core method (P > .05). CONCLUSIONS: Ten- or 12-core biopsy showed a higher detection rate than the other schemes. However, for patients with a prostate-specific antigen concentration of 20 ng/mL or higher, the 6-core systematic biopsy is preferred.
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Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Ultrassonografia de Intervenção/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia com Agulha de Grande Calibre/métodos , Humanos , Biópsia Guiada por Imagem/métodos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Próstata/diagnóstico por imagem , Próstata/patologia , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
Breast cancer has become the biggest threat to female health. Ultrasonic diagnosis of breast cancer based on artificial intelligence is basically a classification of benign and malignant tumors, which does not meet clinical demand. Besides, the current target detection method performs poorly in detecting small lesions, while it is clinically required to detect nodules below 2 mm. The objective of this study is to (a) propose a diagnostic method based on Breast Imaging Reporting and Data System (BI-RADS) and (b) increase its detectability of small lesions. We modified the framework of Faster R-CNN (Faster Region-based Convolutional Neural Network) by introducing multi-scale feature extraction and multi-resolution candidate bound extraction into the network. Then, it was trained using 852 images of BI-RADS C2, 739 images of C3, and 1662 images of malignancy (BI-RADS 4a/4b/4c/5/6). We compared our model with unmodified Faster R-CNN and YOLO v3 (You Only Look Once v3). The mean average precision (mAP) is significantly increased to 0.913, while its average detection speed is slightly declined to 4.11 FPS (frames per second). Meanwhile, its detectivity of small lesions is effectively improved. Moreover, we also tentatively applied our model on video sequences and got satisfactory results. We modified Faster R-CNN and trained it partly based on BI-RADS. Its detectability of lesions, as well as small nodules, was significantly improved. In view of wide coverage of dataset and satisfactory test results, our method can basically meet clinical needs.
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Mama/diagnóstico por imagem , Redes Neurais de Computação , Ultrassonografia Mamária/métodos , Neoplasias da Mama/diagnóstico por imagem , Conjuntos de Dados como Assunto , Feminino , Humanos , Processamento de Imagem Assistida por ComputadorRESUMO
STATEMENT OF PROBLEM: Although palladium-silver alloys have been marketed for over 3 decades for metal-ceramic restorations, understanding of the corrosion behavior of current alloys is incomplete; this understanding is critical for evaluating biocompatibility and clinical performance. PURPOSE: The purpose of this in vitro study was to characterize the corrosion behavior of 3 representative Pd-Ag alloys in simulated body fluid and oral environments and to compare them with a high-noble Au-Pd alloy. The study obtained values of important electrochemical corrosion parameters, with clinical relevance, for the rational selection of casting alloys. MATERIAL AND METHODS: The room temperature in vitro corrosion characteristics of the 3 Pd-Ag alloys and the high-noble Au-Pd alloy were evaluated in 0.9% NaCl, 0.09% NaCl, and Fusayama solutions. After simulated porcelain firing heat treatment, 5 specimens of each alloy were immersed in the electrolytes for 24 hours. For each specimen, the open-circuit potential (OCP) was first recorded, and linear polarization was then performed from -20 mV to +20 mV (versus OCP) at a rate of 0.125 mV/s. Cyclic polarization was subsequently performed on 3 specimens of each alloy from -300 mV to +1000 mV and back to -300 mV (versus OCP) at a scanning rate of 1 mV/s. The differences in OCP and corrosion resistance parameters (zero-current potential and polarization resistance) among alloys and electrolyte combinations were compared with the 2-factor ANOVA (maximum-likelihood method) with post hoc Tukey adjustments (α=.05). RESULTS: The 24-hour OCPs and polarization resistance values of the 3 Pd-Ag alloys and the Au-Pd alloy were not significantly different (P=.233 and P=.211, respectively) for the same electrolyte, but significant differences were found for corrosion test results in different electrolytes (P<.001 and P=.032, respectively). No significant interaction was found between the factors of alloy and electrolyte (P=.249 and P=.713, respectively). The 3 Pd-Ag silver alloys appeared to be resistant to chloride ion corrosion, and passivation and de-alloying were identified for these alloys. CONCLUSIONS: The Pd-Ag alloys test results showed excellent in vitro corrosion resistance and were equivalent to those of the high-noble Au-Pd alloy in simulated body fluid and oral environments. Passivation, de-alloying, and formation of a AgCl layer were identified as possible corrosion mechanisms for Pd-Ag alloys.
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Corrosão , Ligas Dentárias/química , Paládio/química , Prata/química , Eletroquímica , Eletrólitos , Humanos , Técnicas In Vitro , Teste de Materiais , PotenciometriaRESUMO
Anaplastic lymphoma kinase (ALK) is a highly attractive therapeutic target for the treatment of some non-small cell lung cancer patients. This Letter describes the further SAR exploration on the novel 3-sulfonylpyrazol-4-amino pyrimidine scaffold. This work identified a compound 53 with very good in vitro/in vivo efficacies, good DMPK properties together with better hERG tolerability and it is currently being profiled for the evaluation as a potential pre-clinical candidate.
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Antineoplásicos/farmacologia , Desenho de Fármacos , Inibidores de Proteínas Quinases/farmacologia , Pirazóis/síntese química , Pirazóis/farmacologia , Pirimidinas/síntese química , Pirimidinas/farmacologia , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Quinase do Linfoma Anaplásico , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cães , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Camundongos , Modelos Moleculares , Estrutura Molecular , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Pirazóis/química , Pirimidinas/química , Ratos , Receptores Proteína Tirosina Quinases/metabolismo , Relação Estrutura-AtividadeRESUMO
AIM: To evaluate whether the effect of dendritic cells (DCs) on chronic obstructive pulmonary disease (COPD) can be relieved by blocking CCL20. METHODS: 30 Wistar rats were randomly divided into three groups: control, COPD, and COPD treated with CCL20 monoclonal antibody. In the latter two groups, COPD was induced by four-week cigarette smoke exposure and trachea injection of lipopolysaccharide solution on two occasions. CCL20 monoclonal antibody was injected intraperitoneally on the first day. All animals were sacrificed on the 29th day. Pathomorphology of the lung and bronchiole was analyzed using hematoxylin and eosin staining. The CCR6 content in the bronchoalveolar lavage fluid was detected using ELISA. DC distribution in the lung was examined by immunohistochemistry for OX62. RESULTS: COPD rat models showed pathological alterations similar to those in COPD patients. DCs, CCR6, and the severity of emphysema were significantly increased in the COPD group than in controls (all P values <0.001), and they were significantly reduced after anti-CCL20 treatment compared with the COPD group (all P values <0.05). CONCLUSION: The interaction between CCR6 and its ligand CCL20 promotes the effect of DCs in the COPD pathogenesis, which can be reduced by blocking CCL20.
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Quimiocina CCL20/antagonistas & inibidores , Doença Pulmonar Obstrutiva Crônica/etiologia , Doença Pulmonar Obstrutiva Crônica/prevenção & controle , Fumar/efeitos adversos , Animais , Líquido da Lavagem Broncoalveolar/citologia , Células Dendríticas/imunologia , Modelos Animais de Doenças , Pulmão/fisiopatologia , Masculino , Doença Pulmonar Obstrutiva Crônica/patologia , Distribuição Aleatória , Ratos , Ratos Wistar , Receptores CCR6/efeitos dos fármacosRESUMO
A new series of 2,4-diamino pyrimidine derivatives with a sulfone-substituted pyrazole right side-chain were discovered as potent anaplastic lymphoma kinase inhibitors. Structure-activity relationship of the left side-chain on phenyl substitutions were explored which delivered many potent ALK inhibitors. Among them, 29a showed favorable pharmacokinetic profiles in rats and dogs together with significant antitumor efficacy in EML4-ALK fusion xenograft model.
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Antineoplásicos/farmacologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Pirimidinas/química , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Quinase do Linfoma Anaplásico , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Disponibilidade Biológica , Técnicas de Química Sintética , Cães , Desenho de Fármacos , Descoberta de Drogas , Humanos , Camundongos , Terapia de Alvo Molecular , Proteínas de Fusão Oncogênica/genética , Pirimidinas/farmacologia , Ratos Sprague-Dawley , Receptores Proteína Tirosina Quinases/genética , Relação Estrutura-Atividade , Ensaios Antitumorais Modelo de Xenoenxerto/métodosRESUMO
Clonorchis sinensis infections persist globally among humans. These pathogens mainly inhabit the intrahepatic biliary system. Most individuals with clonorchiasis exhibit mild symptoms. The absence of distinctive symptoms often results in delayed diagnosis and treatment, potentially leading to chronic infection. We herein report a case of a 29-year-old female presented with a year-long history of abdominal distention and dyspepsia. Imaging revealed intrahepatic bile duct dilatation, intrahepatic bile duct cyst, and associated deposits. One month post-cystectomy, the patient developed massive ascites and a significant increase in eosinophil count. After treatment, multiple worms were observed in the drainage tube. Morphological and DNA metagenomic analyses confirmed the presence of C. sinensis. Clinical manifestations of C. sinensis vary widely. Imaging serves as a valuable diagnostic tool in endemic areas, especially in detecting intrahepatic duct dilation where the flukes reside. In addition to intrahepatic bile duct dilation, abnormal echoes within the bile duct and the presence of floating objects in the gallbladder significantly aid in diagnosis. Clinicians may encounter these parasitic diseases unexpectedly, underscoring the importance of understating such cases in routine practice and contributing to our broader understanding of managing similar cases in clinical settings.
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Sono-photodynamic therapy (SPDT) has emerged as a promising treatment modality for triple negative breast cancer (TNBC). However, the hypoxic tumor microenvironment hinders the application of SPDT. Herein, in this study, a multifunctional platform (MnO2/Ce6@MBs) was designed to address this issue. A sono-photosensitizer (Ce6) and a hypoxia modulator (MnO2) were loaded into microbubbles and precisely released within tumor tissues under ultrasound irradiation. MnO2in situ reacted with the excess H2O2 and H+ and produced O2 within the TNBC tumor, which alleviated hypoxia and augmented SPDT by increasing ROS generation. Meanwhile, the reaction product Mn2+ was able to achieve T1-weighted MRI for enhanced tumor imaging. Additionally, Ce6 and microbubbles served as a fluorescence imaging contrast agent and a contrast-enhanced ultrasound imaging agent, respectively. In in vivo anti-tumor studies, under the FL/US/MR imaging guidance, MnO2/Ce6@MBs combined with SPDT significantly reversed tumor hypoxia and inhibited tumor growth in 4T1-tumor bearing mice. This work presents a theragnostic system for reversing tumor hypoxia and enhancing TNBC treatment.
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Fotoquimioterapia , Porfirinas , Neoplasias de Mama Triplo Negativas , Humanos , Animais , Camundongos , Neoplasias de Mama Triplo Negativas/diagnóstico por imagem , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Microbolhas , Compostos de Manganês , Peróxido de Hidrogênio , Linhagem Celular Tumoral , Óxidos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Hipóxia , Porfirinas/farmacologia , Microambiente TumoralRESUMO
Correction for 'MnO2/Ce6 microbubble-mediated hypoxia modulation for enhancing sono-photodynamic therapy against triple negative breast cancer' by Ping Li et al., Biomater. Sci., 2024, https://doi.org/10.1039/d3bm00931a.
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Background: Soft tissue tumors (STTs) are benign or malignant superficial neoplasms arising from soft tissues throughout the body with versatile pathological types. Although Ultrasonography (US) is one of the most common imaging tools to diagnose malignant STTs, it still has several drawbacks in STT diagnosis that need improving. Objectives: The study aims to establish this deep learning (DL) driven Artificial intelligence (AI) system for predicting malignant STTs based on US images and clinical indexes of the patients. Methods: We retrospectively enrolled 271 malignant and 462 benign masses to build the AI system using 5-fold validation. A prospective dataset of 44 malignant masses and 101 benign masses was used to validate the accuracy of system. A multi-data fusion convolutional neural network, named ultrasound clinical soft tissue tumor net (UC-STTNet), was developed to combine gray scale and color Doppler US images and clinic features for malignant STTs diagnosis. Six radiologists (R1-R6) with three experience levels were invited for reader study. Results: The AI system achieved an area under receiver operating curve (AUC) value of 0.89 in the retrospective dataset. The diagnostic performance of the AI system was higher than that of one of the senior radiologists (AUC of AI vs R2: 0.89 vs. 0.84, p=0.022) and all of the intermediate and junior radiologists (AUC of AI vs R3, R4, R5, R6: 0.89 vs 0.75, 0.81, 0.80, 0.63; p <0.01). The AI system also achieved an AUC of 0.85 in the prospective dataset. With the assistance of the system, the diagnostic performances and inter-observer agreement of the radiologists was improved (AUC of R3, R5, R6: 0.75 to 0.83, 0.80 to 0.85, 0.63 to 0.69; p<0.01). Conclusion: The AI system could be a useful tool in diagnosing malignant STTs, and could also help radiologists improve diagnostic performance.
RESUMO
OBJECTIVE: To explore the application feasibility of contrast-enhanced ultrasound (CEUS) plus methylene blue in sentinel lymph node biopsy (SLNB) for breast cancer and determine the ultrasonographic features of sentinel lymph node (SLN). METHODS: The microbubbles of SonoVue were injected subcutaneously and intradermally into tumor side of areola. The images were observed to record the size, number, lymphatic door, aspect ratio, enhanced time and enhanced mode of SLN. Methylene blue was injected into SLN under the guidance of ultrasound. The marked SLNs were dissected for pathological examinations. Based upon the results, the specimens were divided into SLN metastasis and SLN non-metastasis groups. RESULTS: A total of 34 breast cancer patients were recruited. Among them, SLN was detected preoperatively in 31 patients by CEUS and the rate was 91.2%. And the postoperative results showed that 14 were confirmed positive (metastasis group) and 17 negative (non-metastasis group). The sensitivity, specificity, accuracy and false negative rate of CEUS for detecting SLNs were 93.3% (14/15), 100% (16/16), 96.8% (30/31) and 6.7% (1/15) respectively. The model of stepwise regression analysis showed that lymphatic door, aspect ratio and enhanced mode were helpful to differentiate SLN metastasis and SLN non-metastasis groups. CONCLUSIONS: SLNB under the guidance of CEUS plus methylene blue offer prompt and accurate localization with a lower cost. It may enhance the detection rate of SLNB in breast cancer.