RESUMO
OBJECTIVE: Accurate assessment of pressure injuries (PIs) is necessary for a good outcome. Junior and non-specialist nurses have less experience with PIs and lack clinical practice, and so have difficulty staging them accurately. In this work, a deep learning-based system for PI staging and tissue classification is proposed to help improve its accuracy and efficiency in clinical practice, and save healthcare costs. METHOD: A total of 1610 cases of PI and their corresponding photographs were collected from clinical practice, and each sample was accurately staged and the tissues labelled by experts for training a Mask Region-based Convolutional Neural Network (Mask R-CNN, Facebook Artificial Intelligence Research, Meta, US) object detection and instance segmentation network. A recognition system was set up to automatically stage and classify the tissues of the remotely uploaded PI photographs. RESULTS: On a test set of 100 samples, the average precision of this model for stage recognition reached 0.603, which exceeded that of the medical personnel involved in the comparative evaluation, including an enterostomal therapist. CONCLUSION: In this study, the deep learning-based PI staging system achieved the evaluation performance of a nurse with professional training in wound care. This low-cost system could help overcome the difficulty of identifying PIs by junior and non-specialist nurses, and provide valuable auxiliary clinical information.
Assuntos
Aprendizado Profundo , Úlcera por Pressão , Humanos , Úlcera por Pressão/enfermagem , Redes Neurais de Computação , Masculino , FemininoRESUMO
Diagnosing and treating liver fibrosis is a challenging yet crucial endeavor due to its complex pathogenesis and risk of deteriorating into cirrhosis, liver failure, and even hepatic cancer. Herein, a silica cross-linked micelles (SCLMs) based nano-system is developed for both diagnosing and treating liver fibrosis. The SCLMs are first modified with peptide CTCE9908 (CT-SCLMs) and can actively target CXCR4, which is overexpressed in activated hepatic stellate cells (HSCs). To enable diagnosis, an ONOO--responded near-infrared fluorescent probe NOF2 is loaded into the CT-SCLMs. This nano-system can target the aHSCs and diagnose the liver fibrosis particularly in CCl4-induced liver damage, by monitoring the reactive nitrogen species. Furthermore, a step is taken toward treatment by co-encapsulating two anti-fibrosis drugs, silibinin and sorafenib, within the CT-SCLMs. This combined approach results in a significant alleviation of liver injury. Symptoms associated with liver fibrosis, such as deposition of collagen, expression of hydroxyproline, and raised serological indicators show notable improvement. In summary, the CXCR4-targeted nano-system can serve as a promising theragnostic system of early warning and diagnosis for liver fibrosis, offering hope against progression of this serious liver condition.
Assuntos
Células Estreladas do Fígado , Cirrose Hepática , Micelas , Nanomedicina , Cirrose Hepática/metabolismo , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/patologia , Cirrose Hepática/diagnóstico , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/efeitos dos fármacos , Animais , Nanomedicina/métodos , Humanos , Receptores CXCR4/metabolismo , Masculino , Diagnóstico Precoce , CamundongosRESUMO
The chemical identification of the modified heme (the green heme) during chloroperoxidase catalyzed epoxidation of allylbenzene remains unestablished due to its high instability within the protein matrix, the absence of paramagnetically shifted signals, and the difficulty in obtaining crystals of the modified enzyme. We have established the unambiguous structure of the modified prosthetic heme group, which was extracted from the protein matrix using 2D NMR spectroscopy and LC-MS spectrometry. The modified heme was isolated as a µ-oxo dimer that can be quantitatively converted to the corresponding monomer. The depolymerized green heme displayed characteristic NMR signatures of iron porphyrin complexes, but no Nuclear Overhauser Effect was observable to assist in signal assignment. An alternative strategy was applied by removing the iron center of the green heme, resulting in a stable demetallated green porphyrin species. Complete assignment of all the NMR resonances in the demetallated green heme allowed us to establish the molecular architecture of the modified species as a novel N-alkylated heme. Decisive space correlations between the propyl protons of allylbenzene and the γ meso proton coupled with clear dipolar connectivities between the propyl-2H of the substrate and the ß proton in the side chain of the propionic acid at carbon-6 of the porphyrin ring, clearly indicate that allylbenzene was covalently attached to the nitrogen atom of the pyrrole ring III of the prosthetic heme. In this study, the mechanism of green CPO formation and its relation to CPO catalyzed chiral transformations are also discussed. It is concluded that the double-phenyl clamp formed by two phenylalanine residues at the distal heme pocket plays a critical role in fine-tuning substrate orientation that determines the outcome of CPO catalyzed epoxidation of substituted styrenes.
RESUMO
Aldo-keto reductase family 1 member C3 (AKR1C3) serves as a contributor to numerous kinds of tumors, and its expression is elevated in patients with hepatocellular carcinoma (HCC). However, the biological function of AKR1C3 in HCC remains unclear. Here we investigated the role of AKR1C3 in liver carcinogenesis using in vitro and in vivo models. We determined that AKR1C3 is frequently increased in HCC tissues with poor prognosis. Genetically manipulated cells with AKR1C3 construction were examined to highlight the pro-tumoral growth of both wild-type AKR1C3 and mutant in vitro and in vivo. We observed promising treatment effects of AKR1C3 shRNA by intratumoral injection in mice. Mechanically, we demonstrated that the transcription factor heterodimer NRF2/MAFG was able to bind directly to AKR1C3 promoter to activate its transcription. Further, AKR1C3 stabilized PARP1 by decreasing its ubiquitination, which resulted in HCC cell proliferation and low sensitivity of Cisplatin. Moreover, we discovered that the tumorigenic role of AKR1C3 was non-catalytic dependent and the NRF2/MAFG-AKR1C3-PARP1 axis might be one of the important proliferation pathways in HCC. In conclusion, blockage of AKR1C3 expression provides potential therapeutic benefits against HCC.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , 3-Hidroxiesteroide Desidrogenases/genética , Membro C3 da Família 1 de alfa-Ceto Redutase/metabolismo , Animais , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Hidroxiprostaglandina Desidrogenases/genética , Neoplasias Hepáticas/genética , Fator de Transcrição MafG/metabolismo , Camundongos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Poli(ADP-Ribose) Polimerase-1/metabolismo , Proteínas Repressoras/metabolismoRESUMO
Trifluoroacetic acid (TFA) is a very persistent, very mobile substance (vPvM) with potential toxicity, and causes increasing environmental concerns worldwide. Conventional wastewater treatment strategies are inefficient for selective TFA removal in the presence of inorganic anions. Here we show that surface defunctionalized activated carbon felt (DeACF) carrying anion exchange sites exhibits an outstanding adsorption efficiency towards TFA thanks to introduced electrostatic attraction and enhanced interactions between hydrophobic carbon surface and CF3 moieties (qmax = 30 mg/g, Kd = (840 ± 80) L/kg at cTFA = 3.4 mg/L in tap water). Flow-cell experiments demonstrated a strongly favored TFA uptake by DeACF from tap water over Cl- and SO42- but a remarkable co-adsorption of the inorganic water contaminant NO3-. Electro-assisted TFA desorption using 10 mM Na2SO4 as electrolyte and oxidized ACF as anode showed high recoveries of ≥ 87% at low cell voltages (< 1.1 V). Despite an initial decrease in TFA adsorption capacity (by 33%) caused by partial surface oxidation of DeACF after the 1st ad-/desorption cycle, the system stability was fully maintained over the next 4 cycles. Such electro-assisted 'trap&release' approach for TFA removal can be exploited for on-site regenerable adsorption units and as a pre-concentration step combined with degradation technologies.
Assuntos
Poluentes Químicos da Água , Purificação da Água , Adsorção , Ânions , Carvão Vegetal/química , Ácido Trifluoracético/química , Água/química , Poluentes Químicos da Água/químicaRESUMO
Persistent and mobile organic compounds (PMOCs) are often detected micropollutants in the water cycle, thereby challenging the conventional wastewater and drinking water treatment techniques. Carbon-based adsorbents are often less effective or even unable to remove this class of pollutants. Understanding of PMOC adsorption mechanisms is urgently needed for advanced treatment of PMOC-contaminated water. Here, we investigated the effect of surface modifications of activated carbon felts (ACFs) on the adsorption of six selected PMOCs carrying polar or ionic groups. Among three ACFs, defunctionalized ACF bearing net positive surface charge at neutral pH provides the most versatile sorption efficiency for all studied PMOC types representing neutral, anionic and cationic compounds. Ion exchange capacity giving quantitative information of sorbent surface charges at specified pH is recognized as a frequently underestimated key property for evaluating adsorbents aiming at PMOC adsorption. A most recently developed prediction tool for Freundlich parameters in PMOC adsorption was applied and the prediction results are compared to the experimental data. The comparison demonstrates the so far underestimated importance of the sorbent surface chemistry for PMOC adsorption affinity and capacity. PMOC adsorption mechanisms were additionally investigated by adsorption experiments at various temperatures, pH values and electrolyte concentrations. Exothermic sorption was observed for all sorbate-sorbent pairs. Adsorption is improved for ionic PMOCs on AC carrying sites of the same charge (positive or negative) at increased electrolyte concentration, while not affected for neutral PMOCs unless strong electron donor-acceptor yet weak non-Coulombic interactions exist. Our findings will allow for better design and targeted application of activated carbon-based sorbents in water treatment facilities.
Assuntos
Poluentes Químicos da Água , Purificação da Água , Adsorção , Carvão Vegetal , Compostos OrgânicosRESUMO
This study aimed to assess changes in sleep pattern and their influence on people's daily life and emotion during the COVID-19 pandemic. Self-developed questionnaires were used to measure changes in nocturnal sleep, daytime napping, lifestyles and negative emotions in individuals before and after the COVID-19 pandemic. Nine hundred and thirty effective questionnaires were collected in this study. Repeated measures analysis of variance and hierarchical regression analysis were applied. We found that individuals' sleep rhythms were delayed, and sleep duration and sleep latency were increased during the stay-at-home orders. Meanwhile, their exercise levels and learning/working efficiency were decreased, and electronic device use time, annoyance levels and anxiety levels were increased. Delayed sleep patterns affected lifestyles and emotions. Moreover, sleep quality positively predicted learning/working efficiency and exercise levels, and negatively predicted use of electronic devices and negative emotions. Sleep patterns became delayed on weekdays during stay-at-home orders in all four daytime napping groups (no daytime napping, daytime napping as before, more daytime napping and less daytime napping), and the group taking daytime naps as before had a minimal variation, and their lifestyles and emotions were significantly better than those of the other groups. This study demonstrated that under the influence of stress caused by the pandemic, maintaining regular daytime napping was an effective way to stabilize sleep patterns and biological rhythms, keep good lifestyles and alleviate the effect of acute psychological stress, and to prevent and control mental disorders during the pandemic.
Assuntos
COVID-19 , Emoções , Estilo de Vida , Pandemias , Sono/fisiologia , Adolescente , Adulto , COVID-19/epidemiologia , Feminino , Humanos , Masculino , Inquéritos e Questionários , Fatores de Tempo , Adulto JovemRESUMO
OBJECTIVE: Depression is highly prevalent among 1st-year college students, and evening chronotype is an important risk factor associated with depression. This study investigates the mediating role of sleep quality and the moderating role of resilience between chronotype and depressive symptoms. METHODS: A total of 4531 students were included in this cross-sectional study. Mediation and moderated mediation models were applied. RESULTS: The association between chronotype and depressive symptoms was partially mediated by sleep quality, and the direct and indirect effects were moderated by resilience. The negative correlation between chronotype and depressive symptoms was significant in students with low levels of resilience compared with moderate/high levels. The positive correlation between sleep quality and depressive symptoms was strongest in low-level resilience students. CONCLUSION: This study reveals that greater eveningness is associated with poorer sleep quality among 1st-year college students, which may lead to severer depression, and highlights the importance of resilience training in reducing depressive symptoms.
Assuntos
Depressão , Distúrbios do Início e da Manutenção do Sono , Estudos Transversais , Depressão/epidemiologia , Humanos , Sono , Estudantes , Inquéritos e QuestionáriosRESUMO
Here, we characterized a flap endonuclease 1 (FEN1) plus hairpin DNA probe (hpDNA) system, designated the HpSGN system, for both DNA and RNA editing without sequence limitation. The compact size of the HpSGN system make it an ideal candidate for in vivo delivery applications. In vitro biochemical studies showed that the HpSGN system required less nuclease to cleave ssDNA substrates than the SGN system we reported previously by a factor of â¼40. Also, we proved that the HpSGN system can efficiently cleave different RNA targets in vitro. The HpSGN system cleaved genomic DNA at an efficiency of â¼40% and â¼20% in bacterial and human cells, respectively, and knocked down specific mRNAs in human cells at a level of â¼25%. Furthermore, the HpSGN system was sensitive to the single base mismatch at the position next to the hairpin both in vitro and in vivo. Collectively, this study demonstrated the potential of developing the HpSGN system as a small, effective, and specific editing tool for manipulating both DNA and RNA without sequence limitation.
Assuntos
Archaeoglobus fulgidus/enzimologia , Endonucleases Flap/metabolismo , Edição de Genes/métodos , Sequências Repetidas Invertidas , Edição de RNA , Archaeoglobus fulgidus/genética , Pareamento Incorreto de Bases , DNA/química , Sondas de DNA/química , Sondas de DNA/genética , DNA de Cadeia Simples , Escherichia coli/genética , Endonucleases Flap/química , Endonucleases Flap/genética , Endonucleases Flap/isolamento & purificação , Células HEK293 , Humanos , Técnicas In Vitro , Conformação de Ácido Nucleico , RNA/química , Especificidade por SubstratoRESUMO
Cytoplasmic vacuolization usually occurs in cells treated with different agents and substances. We found that LZ-106, an analog of enoxacin, is a potent lysosomotropic agent, contributing to the formation of cytoplasmic vacuoles in cells. Studies of LZ-106-induced vacuolization in H460 cells showed acid environment inside these vacuoles. Further study demonstrated that markers in the late endosomes and lysosomes, like LAMP1 and RAB7, on the surface of the vacuoles, implying that these vacuoles might derive from endosomes and/or lysosomes. By studying the fluorescence intensity of LZ-106, we discovered that LZ-106 tended to locate in acid organelles, and Bafilomycin A1, a V-ATPase inhibitor, was able to suppress its acid organelles localization. Also, we noticed that LZ-106 could induce lysosome stress, involving pH increment and lysosomal membrane damage. Moreover, the expression levels of some lysosome-related proteins, like LAMP1, EEA1, and Cathepsin B, were also altered upon LZ-106 treatment. At last, we confirmed LZ-106 can activate TFEB, a key regulator of lysosomes. Knockdown of TFEB could also reverse LZ-106's effect on vacuolization in H460 cells. Taken together, due to LZ-106's lysosomotropic properties, it is able to accumulate in the acid organelles and induce lysosomal dysfunction in H460 cells, leading to TFEB activation and the following cytoplasmic vacuolization.
Assuntos
Enoxacino/análogos & derivados , Enoxacino/farmacologia , Vacúolos/efeitos dos fármacos , Animais , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Linhagem Celular Tumoral , Citoplasma/metabolismo , Endossomos/metabolismo , Humanos , Lisossomos/química , Macrolídeos/farmacologiaRESUMO
We report the case of a young patient diagnosed with coronavirus disease 2019 with a history of hypertension. The patient improved after antiviral treatment but eventually developed severe respiratory distress syndrome and cardiac insufficiency. His respiratory secretions were tested for nucleic acids and returned negative twice. Computed tomography imaging of the patient showed evidence of viral pneumonia on the 11th day of onset and continued to worsen. The patient was finally intubated and transferred to a higher-level care centre for further treatment. We were very focused on infectious disease protection throughout the treatment, however, suboptimal treatment was provided due to the switch in antihypertensive medication, lack of early nutritional support and fluid restriction management.
Assuntos
Betacoronavirus , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Hipertensão/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/terapia , Antivirais/uso terapêutico , COVID-19 , Humanos , Hipertensão/terapia , Masculino , Pandemias , SARS-CoV-2 , Resultado do Tratamento , Adulto JovemRESUMO
LZ-106, a newly synthetized analog of quinolone, has been shown to be highly effective in non-small cell lung cancer (NSCLC) in both cultured cells and xenograft mouse model with low toxicity, yet the molecular mechanisms still require exploration. Here, we substantiated the involvement of P53 activation in intracellular reactive oxygen species (ROS) generation upon LZ-106 treatment and related P53 to the ROS-induced viability inhibition and apoptosis, which was exhibited in the previous research. P53 was shown to play an indispensable role in the elevated levels of intracellular ROS in LZ-106-treated NSCLC cells through ROS detection. We further identified the anti-proliferation effect of LZ-106 in NSCLC cells through G1 phase cell cycle arrest by cell cycle analysis, with the expression analysis of the key proteins, and discovered that the cell cycle arrest effect is also mediated by induction of ROS in a P53-dependent manner. In addition, the tumor suppression effect exhibited in vivo was demonstrated to be similar to that in vitro, which requires the participation of P53. Thus, LZ-106 is a potent antitumor drug possessing potent proliferation inhibition and apoptosis induction ability through the P53-dependent ROS modulation both in vitro and in vivo.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Enoxacino/análogos & derivados , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Proteína Supressora de Tumor p53/fisiologia , Animais , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB CRESUMO
BACKGROUND: Pneumonia is a serious public health issue and is concerned around the world. This study is to investigate the association between viral load in children with human adenovirus (HAdV) pneumonia and disease severity. METHODS: A total of 1313 cases of children hospitalized in Hunan Provincial People's Hospital due to community acquired pneumonia (CAP) from April 2011 to May 2014 were enrolled in this study. Samples of nasopharyngeal aspirate were collected for the cohort. WHO criteria for CAP grading was emerged for pneumonia severity classification. Real-time fluorescence quantitative PCR (qRT-PCR) was used to detect 12 kinds of respiratory viruses. HAdV types were identified by nested PCR. The relationship between HAdV load and severity of disease was there by analyzed. RESULTS: Finally, 174 cases (174/1313, 13.3%) were positive for HAdV, and HAdV type 7 (HAdV-7) was the main serotype (76/174, 43.7%). Among the 174 cases, 70 cases were with HAdV infection alone and 104 cases were accompanied by other viruses. The patients were divided into mild pneumonia group (n = 108 cases) and severe pneumonia group (n = 66 cases). HAdV load of children in severe pneumonia group was higher than that in mild pneumonia group. Similar result was obtained in the 70 cases with HAdV infection alone after subgrouping. Relevant factors analysis results showed that severe pneumonia children presented lower onset age, more prone to fever, longer fever time, and longer hospital stay compared with that of mild pneumonia children. Children with HAdV-7 infection developed more frequently severe pneumonia. Multivariate regression analysis showed that HAdV load, age, and fever time were risk factors for pneumonia severity. CONCLUSION: The severity of HAdV infection is significantly correlated with viral load and serotype.
Assuntos
Infecções por Adenovirus Humanos/virologia , Adenovírus Humanos/fisiologia , Pneumonia/virologia , Sistema Respiratório/virologia , Carga Viral , Adenovírus Humanos/genética , Adolescente , Criança , Pré-Escolar , Coinfecção , Infecções Comunitárias Adquiridas/virologia , Feminino , Humanos , Lactente , Masculino , Sistema Respiratório/metabolismo , Infecções Respiratórias/virologia , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Previous research has examined the association between parents' and children's posttraumatic stress disorder symptoms (PTSS) after a variety of traumatic events. However, longitudinal parent-child dyadic studies are scarce. METHODS: Independent self-reports were collected from parent-adolescent dyads (n = 688) after the 2008 Wenchuan earthquake. Adolescents (Mean = 15.22 years; 61.63% female) and one of their parents (Mean = 41.04 years; 58.14% female) each reported on their PTSS at 12 (T12m) and 18 months (T18m) following the earthquake. Longitudinal actor-partner interdependence models (APIMs) were used to examine PTSS within dyads. RESULTS: The prevalence rates of probable PTSD at T12m and T18m were 18.90% and 11.92% in adolescents; as well as 22.09% and 15.12% in parents, showing a significant decline over time. After adjusted for earthquake exposure, both maternal and paternal PTSS at T12m prospectively predicted adolescent girls' and boys' PTSS at T18m (mother to daughter: ß = 0.13; mother to son: ß = 0.17; father to daughter: ß = 0.17; father to son: ß = 0.33), while adolescent girls' and boys' PTSS at T12m only predicted maternal PTSS at T18m (daughter to mother: ß = 0.20; son to mother: ß = 0.20), but not paternal PTSS at T18m. LIMITATIONS: Self-reported measures other than clinical reviews were used to collect data. CONCLUSIONS: This study highlights the mutual impacts of adolescent and parental (especially maternal) PTSS after a disaster. Psychological prevention and intervention for adolescent disaster survivors should adopt a whole family approach.
Assuntos
Comportamento do Adolescente/psicologia , Terremotos , Relações Pais-Filho , Pais/psicologia , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Adaptação Psicológica , Adolescente , Adulto , Povo Asiático/psicologia , Criança , China , Desastres , Feminino , Humanos , Estudos Longitudinais , Masculino , Prevalência , Transtornos de Estresse Pós-Traumáticos/psicologiaRESUMO
BACKGROUND: Lower respiratory tract illness is a major cause of morbidity and mortality in children worldwide, however, information about the epidemiological and clinical characteristics of LRTIs caused by HMPV and HBoV in China is limited. OBJECTIVES: Human bocavirus (HBoV) and human metapneumovirus (HMPV) are two important viruses for children with lower respiratory tract infections (LRTI). We aimed to assay the correlation between viral load and clinical characteristics of HBoV and HMPV with LRTI in Changsha, China. METHODS: Nasopharyngeal aspirates (NPAs) from children with LRTI were collected. Real-time PCR was used to screen HBoV and HMPV. Analyses were performed using SPSS 16.0 software. RESULTS: Pneumonia was the most frequent diagnosis. There was no significant difference between HBoV- and HMPV-positive patients in age (P = .506) or hospitalization duration (P = .280); 24.1% and 18.2% were positive for HBoV and HMPV. HBoV infections peaked in summer (32.2%), and HMPV infections peaked in winter (28.9%). The HBoV-positive patients had a shorter hospitalization duration than the HBoV-negative patients (P = .021), and the HMPV-positive patients had a higher prevalence of fever than the HMPV-negative patients (P = .002). The HBoV viral load was significantly higher among patients aged <1 year (P = .006). The mean HBoV and HMPV viral loads were not significantly different between patients with single infections and coinfections. Patients infected with HBoV only were older than those coinfected with HBoV and other respiratory viruses (P = .005). No significant difference was found in the clinical characteristics of patients infected with HMPV only and those coinfected with HMPV and other respiratory viruses. CONCLUSION: Pneumonia was the most frequent diagnosis caused by HBoV and HMPV. Neither HBoV nor HMPV viral load was correlated with disease severity.
Assuntos
Broncopneumonia/epidemiologia , Bocavirus Humano/isolamento & purificação , Metapneumovirus/isolamento & purificação , Infecções por Paramyxoviridae/epidemiologia , Infecções por Parvoviridae/epidemiologia , Adolescente , Distribuição por Idade , Broncopneumonia/patologia , Broncopneumonia/virologia , Criança , Pré-Escolar , China/epidemiologia , Coinfecção , Feminino , Hospitalização , Humanos , Lactente , Recém-Nascido , Tempo de Internação , Masculino , Nasofaringe/virologia , Infecções por Paramyxoviridae/patologia , Infecções por Paramyxoviridae/virologia , Infecções por Parvoviridae/patologia , Infecções por Parvoviridae/virologia , Prevalência , Reação em Cadeia da Polimerase em Tempo Real , Estações do Ano , Carga ViralRESUMO
Lung cancer, especially non-small-cell lung cancer (NSCLC), plays the leading role in cancer which is closely related to a myriad of fatal results. Unfortunately, current molecular mechanisms and clinical treatment of NSCLC still remain to be explored despite the fact that intensive investigations have been carried out in the last two decades. Recently, growing attention to finding exploitable sources of anticancer agents is refocused on quinolone compounds, an antibiotic with a long period of clinic application, for their remarkable cell-killing activity against not only bacteria, but eukaryotes as well. In this study, we found LZ-106, an analog of enoxacin, exhibiting potent inhibitory effects on NSCLC in both cultured cells and xenograft mouse model. We identified apoptosis-inducing action of LZ-106 in NSCLC cells through the mitochondrial and endoplasmic reticulum (ER)-stress apoptotic pathways via Annexin-V/PI double-staining assay, membrane potential detection, calcium level detection and the expression analysis of the key apoptotic proteins. Through comet assay, reactive oxygen species (ROS) detection, the expression analysis of DNA damage response (DDR) marker γ-H2AX and other DDR-related proteins, we also demonstrated that LZ-106 notably induced ROS overproduction and DDR. Interestingly, additional evidence in our findings revealed that DDR and apoptosis could be alleviated in the presence of ROS scavenger N-acetyl-cysteine (NAC), indicating ROS-dependent DDR involvement in LZ-106-induced apoptosis. Thus our data not only offered a new therapeutic candidate for NSCLC, but also put new insights into the pharmacological research of quinolones.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Enoxacino/administração & dosagem , Espécies Reativas de Oxigênio/metabolismo , Acetilcisteína/metabolismo , Animais , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Enoxacino/análogos & derivados , Humanos , Camundongos , Mitocôndrias/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: To assess the accuracy of ultrasound-guided 16G and 18G core needle biopsy for detecting ultrasound visible breast lesions with different sonographic features. METHODS: A total of 955 sonographically detected breast lesions examined with ultrasound-guided core needle biopsy (US-CNB) and subsequently surgically excised from July 2005 to July 2012 were retrospectively reviewed. Histological findings of US-CNB and the surgical specimens were analyzed for agreements, sensitivities, false negative rates, and underestimate rates according to different sonographic features. RESULTS: The pathological results of the US-CNB showed malignant lesions in 84.1%, high-risk lesions in 8.4%, and benign lesions in 7.5% of the samples. The overall agreement rates were 92.4% for 16G CNB and 92.8% for 18G CNB; their complete sensitivities and false negative rates were both 98.6% and 1.4%, respectively; the high-risk underestimate rates and DCIS underestimate rates were 48.0% and 46.2% for 16G CNB vs 53.3% and 41.2% for 18G CNB, showing no significant difference between the two groups (P>0.01). For both 16G and 18G CNB, the agreements were better for mass lesions than for non-mass lesions (P<0.01). For the mass lesions with a diameter no greater than 10 mm, the agreement rates were lower than the overall data (P<0.01). Calcification in the lesions did not affect the agreement rates (P>0.01). CONCLUSION: Ultrasound-guided 16G and 18G CNB are both accurate methods for evaluating ultrasound visible breast mass lesions with a diameter larger than 10 mm.
Assuntos
Biópsia por Agulha/métodos , Mama/patologia , Ultrassonografia Mamária , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha Fina/instrumentação , Biópsia por Agulha Fina/métodos , Biópsia por Agulha/instrumentação , Feminino , Humanos , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Adulto JovemRESUMO
BACKGROUND: To assess the accuracy of ultrasound-guided 16G or 18G core needle biopsy (CNB) for ultrasound-visible breast lesions, and to analyze the effects of lesion features. METHODS: Between July 2005 and July 2012, 4,453 ultrasound-detected breast lesions underwent ultrasound-guided CNB and were retrospectively reviewed. Surgical excision was performed for 955 lesions (566 with 16G CNB and 389 with 18G CNB) which constitute the basis of the study. Histological findings were compared between the ultrasound-guided CNB and the surgical excision to determine sensitivity, false-negative rate, agreement rate, and underestimation rate, according to different lesion features. RESULTS: Final pathological results were malignant in 84.1% (invasive carcinoma, ductal carcinoma in situ, lymphoma, and metastases), high-risk in 8.4% (atypical lesions, papillary lesions, and phyllodes tumors), and benign in 7.5%. False-negative rates were 1.4% for 16G and 18G CNB. Agreement rates between histological findings of CNB and surgery were 92.4% for 16G and 92.8% for 18G CNB. Overall underestimate rates (high-risk CNB becoming malignant on surgery and ductal carcinoma in situ becoming invasive carcinoma) were 47.4% for 16G and 48.9% for 18G CNB. Agreements were better for mass lesions (16G: 92.7%; 18G: 93.7%) than for non-mass lesions (16G, 85.7%; 18G, 78.3%) (P <0.01). For mass lesions with a diameter ≤10 mm, the agreement rates (16G, 83.3%; 18G, 86.7%) were lower (P <0.01). CONCLUSIONS: Ultrasound-guided 16G and 18G CNB are accurate for evaluating ultrasound-visible breast mass lesions with a diameter >10 mm.
Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Papilar/patologia , Tumor Filoide/patologia , Ultrassonografia Mamária , Adulto , Idoso , Biópsia com Agulha de Grande Calibre , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/cirurgia , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/cirurgia , Carcinoma Papilar/diagnóstico por imagem , Carcinoma Papilar/cirurgia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tumor Filoide/diagnóstico por imagem , Tumor Filoide/cirurgia , Prognóstico , Estudos RetrospectivosRESUMO
OBJECTIVE: To evaluate the underestimation of papillary breast lesions diagnosed at ultrasound-guided breast biopsy. METHODS: Totally 4453 ultrasound-guided visible breast lesions that were identified in the Department of Ultrasound, Chinese PLA General Hospital, from April 2005 to April 2012 were retrospectively reviewed. Of 207 papillary lesions that were detected by histologic findings of ultrasound-guided core needle biopsy(US-CNB), 90 underwent surgical excision, 110 were followed up for at least one year, and 7 were lost to follow-up. The histological findings of the US-CNB and the findings of surgical excision were compared to analyze the underestimation rates according to the Breast Imaging Reporting and Data System(BI-RADS)categories of American College of Radiology(ACR)and biopsy methods. RESULTS: Of the 90 papillary lesions underwent surgical excision, 29(32.2%)were underestimated, and 22 malignant lesions were underestimated(24.4%). Of the 23 papillomata with atypical ductal hyperplasia(IDP+ADH), 11(47.8%)were upgraded to malignant. Of the 137 benign intraductal papilloma(IDP)with concordance imaging-histologic findings, 8 lesions were underestimated(5.8%), whereas 10 out of 25(40.0%)IDP with diacordant imaging-histologic findings were underestimated. In total, 17.9% understimation were biopsied by 18G core needle biopsy(CNB)(P=0.017)and 16.0% by 16G CNB(P=0.023), which were significantly higher than vacuum-assisted biopsy(VAB). CONCLUSIONS: VAB is more accurate than 16G or 18G CNB in detecting papillary breast lesions. For high underestimations of IDP+ADH and IDP with discordant imaging-histologic findings, VAB or surgical excisions should be performed.