RESUMEN
Surgeons determine the treatment method for patients with epiglottis obstruction based on its severity, often by estimating the obstruction severity (using three obstruction degrees) from the examination of drug-induced sleep endoscopy images. However, the use of obstruction degrees is inadequate and fails to correspond to changes in respiratory airflow. Current artificial intelligence image technologies can effectively address this issue. To enhance the accuracy of epiglottis obstruction assessment and replace obstruction degrees with obstruction ratios, this study developed a computer vision system with a deep learning-based method for calculating epiglottis obstruction ratios. The system employs a convolutional neural network, the YOLOv4 model, for epiglottis cartilage localization, a color quantization method to transform pixels into regions, and a region puzzle algorithm to calculate the range of a patient's epiglottis airway. This information is then utilized to compute the obstruction ratio of the patient's epiglottis site. Additionally, this system integrates web-based and PC-based programming technologies to realize its functionalities. Through experimental validation, this system was found to autonomously calculate obstruction ratios with a precision of 0.1% (ranging from 0% to 100%). It presents epiglottis obstruction levels as continuous data, providing crucial diagnostic insight for surgeons to assess the severity of epiglottis obstruction in patients.
RESUMEN
BACKGROUND: In-laboratory, polysomnography (PSG) is the gold standard for diagnosing obstructive sleep apnea syndrome (OSAS). However, the long waiting list and sleeping at a hospital make patients hesitate to undergo the examination, thereby delaying diagnosis. During coronavirus disease 2019 (COVID-19) pandemic, sleep labs are almost closed, and the delay is worsening. The home sleep test (HST) enables subjects to be tested at home, a familiar and comfortable environment, without a long waiting list. This study assessed the accuracy of a type III HST in diagnosing OSAS in the Taiwanese population and identified factors affecting the diagnostic accuracy. METHODS: This retrospective study included 67 patients with clinically suspected OSAS. All patients were allocated to receive both PSG and the HST. The apnea-hypopnea index (AHI) measured through PSG was used as the standard. The sensitivity, specificity, and accuracy of the HST in diagnosing and evaluating the severity of OSAS were analyzed. RESULTS: Among the 67 patients, no significant difference was noted in the average AHI values obtained using PSG and the HST ( p = 0.103). The AHI obtained from HST was significantly correlated with that obtained from PSG, with the correlation coefficient being 0.779 ( p < 0.001). The sensitivity, specificity, and accuracy of the HST in diagnosing OSAS were 94.9%, 62.5%, and 91.0%, respectively, and 80.0%, 74.1%, and 77.6% in diagnosing moderate to severe OSAS. Furthermore, the difference in AHIs measured using the two tests were positively correlated with the severity of sleep apnea. CONCLUSION: The HST used in preliminary screening of patients with suspected OSAS achieved an accuracy of >90%. For patients with moderate to severe OSAS, the accuracy was below 80%. Therefore, for patients who receive an OSAS diagnosis through the HST, arrangement of PSG is recommended for determining the severity of the OSAS and giving proper treatment.
Asunto(s)
COVID-19 , Apnea Obstructiva del Sueño , Humanos , Polisomnografía , Estudios Retrospectivos , Sueño , Apnea Obstructiva del Sueño/diagnósticoRESUMEN
This paper describes the fabrication of a structural scaffold consisting of both randomly oriented nanofibers and triangular prism patterns on the scaffold surface using a combination technique of electrospinning and collector templates. The polycaprolactone (PCL) nanofibers were electrospun over a triangular prism pattern mold, which acted as a template. The deposited scaffold was removed from the template to produce a standalone structural scaffold of three-dimensional micropatterned nanofibers. The fabricated structural scaffold was compared with flat randomly oriented nanofibers based on in vitro and in vivo studies. The in vitro study indicated that the structural scaffold demonstrated higher fibroblast cell proliferation, cell elongation with a 13.48 ± 2.73 aspect ratio and 70% fibroblast cell orientation compared with flat random nanofibers. Among the treatment groups, the structural scaffold escalated the wound closure to 92.17% on day 14. Histological staining of the healed wound area demonstrated that the structural scaffold exhibited advanced epithelization of the epidermal layer accompanied by mild inflammation. The proliferated fibroblast cells and collagen fibers in the structural scaffold appeared denser and arranged more horizontally. These results determined the potential of micropatterned scaffolds for stimulating cell behavior and their application for wound healing.
RESUMEN
BACKGROUND: Much attention has been focused on environmental risk factors and their roles in eczema development. In this regard, the specific eczema risk factors in Taiwan were relatively unknown. As such, this study investigated the common indoor risk factors present in Taiwanese households. AIMS: To discuss the effects of several indoor risk factors on the prevalence of atopic eczema in Taiwan. MATERIALS AND METHODS: A cross-sectional, population-based study was performed in Kaohsiung, Taiwan, using both survey investigation and fungal culturing. A total of 998 participants were enrolled in the survey, with 513 participants selected for fungal culture. Risks of atopic eczema were calculated as odds ratios for various risk factors using logistic regression. The correlation between potential risk factors and the fungal level was analyzed with linear regression. RESULTS: Pet and house plants have an adjusted odds ratio of 1.434 (95% CL: 1.011-2.033) and 1.820 (95% CL: 1.229-2.696), respectively. Additionally, smoking was shown to possess an odds ratio of 1.461 (95% CL: 1.064-2.006). Wood wall has an adjusted odds ratio of 2.143 (95% CL: 1.235-3.658). Frequent bedroom shower use (ß = 0.254) and hours of opened windows (ß = 0.106) have shown significant positive associations with indoor fungal level. CONCLUSION: Pets, house plants, and smoking were concluded to be major risk factors for atopic eczema. Wood wall remained controversial due to its limited sample size and possible confounders. Bedroom shower and window-opening have been shown to increase mold growth, but the lack of association with eczema suggested other allergens besides mold to be the primary eczema trigger.
RESUMEN
Exploring strategies to treat cancer has always been an aim of medical researchers. One of the available strategies is to use targeted therapy drugs to make the chromosomes in cancer cells unstable such that cell death can be induced, and the elimination of highly proliferative cancer cells can be achieved. Studies have reported that the mitotic defects and micronuclei in cancer cells can be used as biomarkers to evaluate the instability of the chromosomes. Researchers use these two biomarkers to assess the effects of drugs on eliminating cancer cells. However, manual work is required to count the number of cells exhibiting mitotic defects and micronuclei either directly from the viewing window of a microscope or from an image, which is tedious and creates errors. Therefore, this study aims to detect cells with mitotic defects and micronuclei by applying an approach that can automatically count the targets. This approach integrates the application of a convolutional neural network for normal cell identification and the proposed color layer signature analysis (CLSA) to spot cells with mitotic defects and micronuclei. This approach provides a method for researchers to detect colon cancer cells in an accurate and time-efficient manner, thereby decreasing errors and the processing time. The following sections will illustrate the methodology and workflow design of this study, as well as explain the practicality of the experimental comparisons and the results that were used to validate the practicality of this algorithm.
Asunto(s)
Aprendizaje Profundo , Neoplasias , Algoritmos , Núcleo Celular , Procesamiento de Imagen Asistido por Computador , Neoplasias/diagnóstico , Redes Neurales de la ComputaciónRESUMEN
A thermally activated shape memory polymer based on the mixture of polycaprolactone (PCL) and polydimethylsiloxane (PDMS) was fabricated into the nanofibre mesh using the electrospinning process. The added percentages of the PDMS segment in the PCL-based polymer influenced the mechanical properties. Polycaprolactone serves as a switching segment to adjust the melting temperature of the shape memory electro-spun PCL-PDMS scaffolds to our body temperature at around 37 °C. Three electro-spun PCL-PDMS copolymer nanofibre samples, including PCL6-PDMS4, PCL7-PDMS3 and PCL8-PDMS2, were characterised to study the thermal and mechanical properties along with the shape memory responses. The results from the experiment showed that the PCL switching segment ratio determines the crystallinity of the copolymer nanofibres, where a higher PCL ratio results in a higher degree of crystallinity. In contrast, the results showed that the mechanical properties of the copolymer samples decreased with the PCL composition ratio. After five thermomechanical cycles, the fabricated copolymer nanofibres exhibited excellent shape memory properties with 98% shape fixity and above 100% recovery ratio. Moreover, biological experiments were applied to evaluate the biocompatibility of the fabricated PCL-PDMS nanofibre mesh. Owing to the thermally activated shape memory performance, the electro-spun PCL-PDMS fibrous mesh has a high potential for biomedical applications such as medical shrinkable tubing and wire.
RESUMEN
BACKGROUND: 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (18F-FDG PET) has the potential to detect various types of cancers, including thyroid cancer (TC), at a potentially curable stage. Increased uptake of 18F-FDG was observed in anaplastic and poorly differentiated thyroid cancer cells, and PET-positive tumors are more likely to be resistant to 131I treatment. As cancer stem cells (CSCs) possess a dedifferentiated phenotype and are resistant to many anticancer therapies, we hypothesized that the expression of CSC-related markers is correlated with the ability of tumor cells in TC to uptake FDG. METHODS: The present study cohort included 12 patients with TC, who underwent 18F-FDG PET/CT imaging before surgery. Quantitative polymerase chain reaction (QPCR) and immunohistochemical (IHC) staining were performed to analyze the expression patterns of gene markers related to embryonic stem (ES) cells and CSCs in TC. RESULTS: The mRNA expression levels of CSC- (CD133 and CD44) and ES-related genes (Oct4 and Nanog) were higher in TC tissue than in normal thyroid tissue, whereas the mRNA expression levels of thyroid-specific genes (Tg, TSHR, and TTF1) were higher in normal thyroid tissue than in TC tissue. There was a positive and statistically significant correlation between FDG uptake (SUV
Asunto(s)
Fluorodesoxiglucosa F18/química , Células Madre Neoplásicas/efectos de la radiación , Radiofármacos/química , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/tratamiento farmacológico , Antígeno AC133/metabolismo , Transporte Biológico , Diferenciación Celular/efectos de la radiación , Relación Dosis-Respuesta en la Radiación , Fluorodesoxiglucosa F18/farmacología , Humanos , Receptores de Hialuranos/metabolismo , Radioisótopos de Indio/química , Tomografía Computarizada por Tomografía de Emisión de Positrones , ARN Mensajero , Receptores de Tirotropina/metabolismo , Glándula Tiroides/citología , Distribución Tisular , Tomografía Computarizada por Rayos X , Factor Trefoil-1/metabolismoRESUMEN
OBJECTIVE: This study aimed to determine the impact or survival of low skeletal muscle mass (SMM) among patients with oral squamous cell carcinoma (OSCC) undergoing primary surgery. DESIGN: This study was a retrospective cohort study. SETTING: Oral squamous cell carcinoma patients treated at our referral centre from April 2005 to March 2014 were examined. PARTICIPANTS: The cohort comprised 276 patients with OSCC undergoing primary surgery. MAIN OUTCOME MEASURES: Estimated SMM was measured by calculating the cervical skeletal muscle mass from a CT scan of the head and neck. The 5-year overall survival (OS) and disease-specific survival (DSS) were analysed using a multivariable Cox regression model. RESULTS: There were 276 patients with a male-to-female ratio of 12:1. A low SMM (<47.5 cm2 /m2 ) was associated with worse survival. After adjustment for other factors, the result remained robust for OS (hazard ratio [HR] 1.74, 95% confidence interval [CI] 1.14-2.67) and disease-specific survival (HR 1.67, 95% CI 1.04-2.67). In the subgroup analysis, worse OS and DSS were particularly noted in male patients (HR = 1.90, 95% CI 1.22-2.97; HR = 1.91, 95% CI 1.27-3.19) and in those younger than 60 years of age (HR = 1.91, 95% CI 1.14-3.22; HR = 2.12, 95% CI 1.23-3.64) with low SMM. CONCLUSIONS: Low SMM was a significant independent factor that was associated with lower survival in patients who have oral cavity cancers and are undergoing primary surgery. Preoperative CT scans of the head and neck could be utilised to evaluate SMM, predict treatment outcomes and facilitate nutrition management.
Asunto(s)
Neoplasias de la Boca/mortalidad , Sarcopenia/complicaciones , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Adulto , Factores de Edad , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/complicaciones , Neoplasias de la Boca/cirugía , Estudios Retrospectivos , Factores de Riesgo , Sarcopenia/mortalidad , Sarcopenia/patología , Factores Sexuales , Carcinoma de Células Escamosas de Cabeza y Cuello/complicaciones , Carcinoma de Células Escamosas de Cabeza y Cuello/cirugía , Tasa de SupervivenciaRESUMEN
Gold nanorods (GNRs) with exceptional photothermal properties have held promising potential for application in the biomedical field. In this study, the authors achieved photothermal ablation by polyethylene glycol (PEG)-functionalised GNRs. Well-dispersed and uniform GNRs were produced through a seed-mediated growth method. A thermal camera was used to scrutinise the temperature distribution and efficiency of the photothermal properties of the GNRs, which were irradiated by an 808â nm laser on a silicon chip. They observed that the GNRs provided about a 5°C temperature increase and produced hyperthermia efficiently. Since GNRs need to be surface tailored with a biocompatible material rather than cetyltrimethylammonium bromide (CTAB), they chose methoxyl PEG thiol to modify the GNRs. By taking advantage of the alkaline environment that assists this functionalisation, they accomplished about 89% removal of CTAB and identified a PEG layer on the surface of the GNRs. The GNR biocompatibility was considerably improved without any shift of the optical properties. Hepatocellular carcinoma cells were incubated with GNRs for 24â h and then were irradiated with a near-infrared laser for 3â min. Few cells remained alive, which demonstrated the photothermal ablation ability of the GNRs.
Asunto(s)
Carcinoma Hepatocelular/terapia , Oro/química , Neoplasias Hepáticas/terapia , Nanopartículas del Metal/uso terapéutico , Fototerapia/métodos , Polietilenglicoles/química , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Materiales Biocompatibles Revestidos/síntesis química , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/uso terapéutico , Ensayos de Selección de Medicamentos Antitumorales , Calor , Humanos , Neoplasias Hepáticas/patología , Ensayo de Materiales , Nanopartículas del Metal/química , Nanotubos/químicaRESUMEN
OBJECTIVE: We examined whether dynamic margin criteria margin-to-thickness (MTR) ratio has superior predictive value compared with the resection margin or tumour thickness alone in the survival outcome in oral squamous cell carcinoma (OSCC). DESIGN: This is a retrospective cohort study. SETTING: Oral squamous cell carcinoma patients treated in Kaohsiung Veterans General Hospital Cancer Center between January 2006 and December 2013. PARTICIPANTS: A cohort of 302 patients with OSCC who had undergone surgical management. MAIN OUTCOMES MEASURES: Log MTR was calculated for each patient, and survival data were analysed using a multivariable Cox regression model. Discriminative analysis was performed using chi-square, Akaike information criterion (AIC) and Harrell's C tests. RESULTS: After assessing for discriminative ability, the linear trend of log MTR surpassed those of resection margin and tumour thickness in chi-square, AIC and Harrell's C tests for the advanced pathologic T (pT) category. A multivariate Cox proportional hazard regression model revealed that log MTR <33% was associated with less favourable 5-year disease-specific survival (DSS) (P = 0.006) in the entire oral cancer study cohort. Other significant factors included perineural invasion (P = 0.021), pT category, (P = 0.005), pathologic N category (P < 0.001) and differentiation category (P = 0.022). CONCLUSIONS: Log MTR < 33% may be a predictor of less favourable outcome in the DSS of OSCC. Log MTR outperformed both resection margin and tumour thickness alone in terms of discriminative analysis. Our study could help in presurgical planning for high-risk patients and in aiding the decision-making process for adjuvant treatment.
Asunto(s)
Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Neoplasias de la Boca/patología , Neoplasias de la Boca/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Bases de Datos Factuales , Femenino , Humanos , Masculino , Márgenes de Escisión , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Medición de Riesgo , Análisis de SupervivenciaRESUMEN
Abstract Introduction: Peritonsillar abscess is the most common deep neck infection. The infectious microorganism may be different according to clinical factors. Objective: To identify the major causative pathogen of peritonsillar abscess and investigate the relationship between the causative pathogen, host clinical factors, and hospitalization duration. Methods: This retrospective study included 415 hospitalized patients diagnosed with peritonsillar abscess who were admitted to a tertiary medical center from June 1990 to June 2013. We collected data by chart review and analyzed variables such as demographic characteristics, underlying systemic disease, smoking, alcoholism, betel nut chewing, bacteriology, and hospitalization duration. Results: A total of 168 patients had positive results for pathogen isolation. Streptococcus viridans (28.57%) and Klebsiella pneumoniae (23.21%) were the most common microorganisms identified through pus culturing. The isolation rate of anaerobes increased to 49.35% in the recent 6 years (p = 0.048). Common anaerobes were Prevotella and Fusobacterium spp. The identification of K. pneumoniae increased among elderly patients (age > 65 years) with an odds ratio (OR) of 2.76 (p = 0.03), and decreased in the hot season (mean temperature > 26 °C) (OR = 0.49, p = 0.04). No specific microorganism was associated with prolonged hospital stay. Conclusion: The most common pathogen identified through pus culturing was S. viridans, followed by K. pneumoniae. The identification of anaerobes was shown to increase in recent years. The antibiotics initially selected should be effective against both aerobes and anaerobes. Bacterial identification may be associated with host clinical factors and environmental factors.
Resumo Introdução: O Abscesso Peritonsilar é a infecção cervical profunda mais comum. O microrganismo infeccioso pode ser diferente de acordo com os fatores clínicos. Objetivo: Identificar o principal agente causador do abscesso peritonsilar e investigar a relação entre o patógeno causador, os fatores clínicos do hospedeiro e a duração da hospitalização. Método: Este estudo retrospectivo incluiu 415 pacientes hospitalizados diagnosticados com abscesso peritonsilar que foram internados em um centro médico terciário de junho de 1990 a junho de 2013. Coletamos dados através da análise dos arquivos médicos dos pacientes e analisamos variáveis como características demográficas, doença sistêmica subjacente, tabagismo, alcoolismo, hábito de mascar noz de betel, bacteriologia e duração da hospitalização. Resultados: Um total de 168 pacientes apresentaram resultados positivos para isolamento de patógenos. Streptococcus viridans (28,57%) e Klebsiella pneumoniae (23,21%) foram os microrganismos mais comuns identificados pela cultura da secreção. A taxa de isolamento de anaeróbios aumentou para 49,35% nos últimos 6 anos (p = 0,048). Os anaeróbios comuns foram Prevotella e Fusobacterium spp. A identificação de K. pneumoniae aumentou em pacientes idosos (idade > 65 anos) com razão de chances (Odds Ratio - OR) de 2,76 (p = 0,03) e diminuiu na estação do calor (temperatura média > 26 °C) (OR = 0,49, p = 0,04). Nenhum microrganismo específico foi associado à hospitalização prolongada. Conclusão: O patógeno mais comumente identificado através da cultura de secreção foi S. viridans, seguido por K. pneumoniae. A identificação de anaeróbios mostrou ter aumentado nos últimos anos. Os antibióticos selecionados inicialmente devem ser efetivos contra aeróbios e anaeróbios. A identificação bacteriana pode estar associada a fatores clínicos e fatores ambientais do hospedeiro.
Asunto(s)
Humanos , Adolescente , Adulto , Persona de Mediana Edad , Adulto Joven , Absceso Peritonsilar/microbiología , Infecciones por Bacterias Grampositivas/microbiología , Fusobacterium necrophorum/aislamiento & purificación , Bacterias Grampositivas/aislamiento & purificación , Infecciones por Klebsiella , Absceso Peritonsilar/diagnóstico , Absceso Peritonsilar/terapia , Estudios Retrospectivos , Factores de Riesgo , Infecciones por Bacterias Grampositivas/terapia , Prevotella , Estreptococos Viridans/aislamiento & purificación , Infecciones por Fusobacterium/microbiología , Klebsiella pneumoniae/aislamiento & purificación , Antibacterianos/uso terapéuticoRESUMEN
BACKGROUND: With a global rising trend in prevalence of allergic diseases, more attention has been paid to investigation of environmental risk factors. Many risk factors have so far been identified. However, novel risk factors specific to Taiwanese environment and lifestyle were still relatively unknown. OBJECTIVE: To investigate the potential effects of a number of little-known indoor risk factors on the frequency of doctor's visit for respiratory problems in context of Taiwanese environment and lifestyle. METHODS: A cross-sectional, population-based study was performed on a 861 participants around Kaohsiung area, Taiwan. Survey investigation was employed to assess the household environment and the frequency of doctor's visit for respiratory problems. RESULTS: Participants who performed "daily cleaning" was shown to have a significantly (p=0.007) higher mean number of doctor's visits in comparison to those who did not. Similar observation was made for participants who periodically took out beddings (p=0.042). Age had a significant positive correlation (linear regression ß 0.089) with frequency of respiratory problems. CONCLUSION: The habit of daily cleaning was implicated as a potential indoor risk factor due to the unique nature of Taiwanese cleaning habit and close contact with cleaning supplies, which could serve as chemical irritants. Bedding takeout was predicted to be an indicator of chronic allergies rather than an actual risk factor. However, both were controversial in their role as potential indoor risk factor, and required further examination.
Asunto(s)
Contaminación del Aire Interior/efectos adversos , Citas y Horarios , Asma/etiología , Asma/epidemiología , Estudios Transversales , Femenino , Humanos , Masculino , Factores de Riesgo , Taiwán , Clima TropicalRESUMEN
INTRODUCTION: Peritonsillar abscess is the most common deep neck infection. The infectious microorganism may be different according to clinical factors. OBJECTIVE: To identify the major causative pathogen of peritonsillar abscess and investigate the relationship between the causative pathogen, host clinical factors, and hospitalization duration. METHODS: This retrospective study included 415 hospitalized patients diagnosed with peritonsillar abscess who were admitted to a tertiary medical center from June 1990 to June 2013. We collected data by chart review and analyzed variables such as demographic characteristics, underlying systemic disease, smoking, alcoholism, betel nut chewing, bacteriology, and hospitalization duration. RESULTS: A total of 168 patients had positive results for pathogen isolation. Streptococcus viridans (28.57%) and Klebsiella pneumoniae (23.21%) were the most common microorganisms identified through pus culturing. The isolation rate of anaerobes increased to 49.35% in the recent 6 years (p=0.048). Common anaerobes were Prevotella and Fusobacterium spp. The identification of K. pneumoniae increased among elderly patients (age>65 years) with an odds ratio (OR) of 2.76 (p=0.03), and decreased in the hot season (mean temperature>26°C) (OR=0.49, p=0.04). No specific microorganism was associated with prolonged hospital stay. CONCLUSION: The most common pathogen identified through pus culturing was S. viridans, followed by K. pneumoniae. The identification of anaerobes was shown to increase in recent years. The antibiotics initially selected should be effective against both aerobes and anaerobes. Bacterial identification may be associated with host clinical factors and environmental factors.
Asunto(s)
Bacterias Grampositivas/aislamiento & purificación , Infecciones por Bacterias Grampositivas/microbiología , Absceso Peritonsilar/microbiología , Adolescente , Adulto , Antibacterianos/uso terapéutico , Infecciones por Fusobacterium/microbiología , Fusobacterium necrophorum/aislamiento & purificación , Infecciones por Bacterias Grampositivas/terapia , Humanos , Infecciones por Klebsiella , Klebsiella pneumoniae/aislamiento & purificación , Persona de Mediana Edad , Absceso Peritonsilar/diagnóstico , Absceso Peritonsilar/terapia , Prevotella , Estudios Retrospectivos , Factores de Riesgo , Estreptococos Viridans/aislamiento & purificación , Adulto JovenRESUMEN
The original hygiene hypothesis declares "more infections in early childhood protect against later atopy". According to the hygiene hypothesis, the increased incidence of allergic disorders in developed countries is explained by the decrease of infections. Epithelial cells and dendritic cells play key roles in bridging the innate and adaptive immune systems. Among the various pattern-recognition receptor systems of epithelial cells and dendritic cells, including toll-like receptors (TLRs), nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) and others, TLRs are the key systems of immune response regulation. In humans, TLRs consist of TLR1 to TLR10. They regulate cellular responses through engagement with TLR ligands, e.g., lipopolysaccharides (LPS) acts through TLR4 and dsRNA acts through TLR3, but there are certain common components between these two TLR pathways. dsRNA activates epithelial cells and dendritic cells in different directions, resulting in allergy-related Th2-skewing tendency in epithelial cells, and Th1-skewing tendency in dendritic cells. The Th2-skewing effect by stimulation of dsRNA on epithelial cells could be suppressed by the presence of LPS above some threshold. When LPS level decreases, the Th2-skewing effect increases. It may be via these interrelated networks and related factors that LPS modifies the allergic responses and provides a plausible mechanism of the hygiene hypothesis. Several hygiene hypothesis-related phenomena, seemingly conflicting, are also discussed in this review, along with their proposed mechanisms.
Asunto(s)
Hipótesis de la Higiene , Lipopolisacáridos/inmunología , Infecciones por Virus ARN/complicaciones , Hipersensibilidad Respiratoria/etiología , Animales , Células Dendríticas , Células Epiteliales , Humanos , Infecciones por Virus ARN/inmunología , Virus ARN , ARN Bicatenario , Hipersensibilidad Respiratoria/inmunología , Hipersensibilidad Respiratoria/prevención & control , Hipersensibilidad Respiratoria/virologíaRESUMEN
Prostate cancer is a complex disease that can be relatively harmless or extremely aggressive. Although androgen-deprivation therapy is a commonly used treatment for men with prostate cancer, the adverse effects can be detrimental to patient health and quality of life. Therefore, identifying new target genes for tumor growth will enable the development of novel therapeutic intervention. TPX2 plays a critical role in chromosome segregation machinery during mitosis. Low rates of chromosome missegregation can promote tumor development, whereas higher levels might promote cell death and suppress tumorigenesis. Hence, the strategy of promoting cell death by inducing massive chromosome missegregation has been a therapeutic application for selectively eliminating highly proliferating tumor cells. RNAi was used for TPX2 protein expression knockdown, and a clonogenic assay, immunostaining, double thymidine block, image-cytometry analysis, and tumor spheroid assay were used to analyze the role of TPX2 in tumor cell growth, cell cycle progression, multinuclearity, ploidy, and tumorigenicity, respectively; finally, Western blotting was used to analyze anticancer mechanisms in TPX2 targeting. We demonstrated that targeting TPX2 reduced cell cycle regulators and chromosome segregation genes, resulting in increased cell micronucleation. Moreover, TPX2 depletion led to prostate cancer cell growth inhibition, increased apoptosis, and reduced tumorigenesis. These results confirmed the therapeutic potential of targeting TPX2 in prostate cancer treatment. Moreover, we found that TPX2 silencing led to deregulation of CDK1, cyclin B, securin, separase, and aurora A proteins; by contrast, p21 mRNA was upregulated. We also determined the molecular mechanisms for TPX2 targeting in prostate cancer cells. In conclusion, our study illustrates the power of TPX2 as a potential novel target gene for prostate cancer treatment.
RESUMEN
Hepatocellular carcinoma (HCC) remains one of the most difficult cancers to treat, with chemotherapies being relatively ineffective. Therefore, a better knowledge of molecular hepatocarcinogenesis will provide opportunities for designing targeted therapies. TPX2 (targeting protein for Xklp2) is overexpressed as a consequence of oncogenic alterations and is likely to alter the proper regulation of chromosome segregation in cancer cells. Disrupting the machinery which is responsible for mitosis and chromosome instability in cancer cells can be one of the most successful strategies for cancer therapy. Therefore, we consider the targeting TPX2 could provide novel therapeutic strategies for cancer. In this study, increased TPX2 protein expression was present in 16 (42%) of 38 primary HCCs and was associated with advanced stage, distant metastatic HCCs and poor prognosis. Knockdown of TPX2 inhibited cancer cell growth and downregulation of cyclin A, cyclin E and CDK2 proteins. However, over-expressed EGFP-TPX2 protein enhanced the in vitro tumor spheroid formation and rescued the TPX2 depleted cell growth. Targeting TPX2 caused a rising impaired chromosomal instability resulting in multinuclearity, cell cycle progression arrest, apotosis, senescence and an increased polyploidy in cells. An image-cytometry analysis revealed cell cycle progression arrest after TPX2 inhibition. A correlation was observed between the downregulation of the protein levels of genes related to chromosomal segregation and spindle assembly checkpoint (securin, seprase, Aurora A, Aurora B, Cyclin B1, Cyclin B2, MPS1, BUB1, BUB3, MAD1 and MAD2) and increased cell ploidy, indicating mitotic progression failure and the loss of the balance of genomic instability. In vitro tumor spheroid assay and in vivo xenografts mouse model showed a therapeutic opportunity. Our findings indicate that targeting TPX2 lead to suppress tumorigenicity in liver cancer cells, suggesting that TPX2 is a potential target for anticancer therapy in HCC.
RESUMEN
OBJECTIVE: To discuss the effect of lesser-known potential risk factors, such as bedroom showers, on the prevalence of allergic rhinitis. METHOD: A cross-sectional, population-based study was performed using both survey and fungal culturing in southern Taiwan. There were 998 participants enrolled in the survey, and 513 sets of fungal culture obtained. With score for allergic rhinitis (SFAR) more than 7, the patient was defined to have allergic rhinitis. Risks of allergic rhinitis were calculated as odds ratios for various predicted risk factors by logistic regression. Correlation between predicted risk factors and fungal level were examined with linear regression. RESULTS: The adjusted odds ratio of frequently using bedroom shower to having allergic rhinitis was 1.572 (95% confidence interval: 1.090-2.265), and 0.962 for people with older age to have AR (95% confidence interval: 0.949-0.976). As to the 24-hour fungal level, the standardized coefficient was 0.254 for frequent use of bedroom shower, and 0.106 for window open hours. CONCLUSIONS: Use of bedroom shower is a potential risk factor for allergic rhinitis development.
RESUMEN
Importance: Inflammatory status is associated with outcome in oral squamous cell carcinoma (OSCC). Combining the preoperative neutrophil to lymphocyte ratio (NLR) and histopathologic features may provide clinicians with more exact information regarding the prognosis of OSCC. Objective: To compare the prognostic performance of the routinely used pathologic TNM staging with a new staging category that incorporates the NLR and histopathologic features. Design, Setting, and Participants: This retrospective cohort study included 396 patients with newly diagnosed OSCC who underwent major surgery at a medical center from January 1, 2006, through December 31, 2013. Follow-up was completed on October 31, 2015, and data analysis was performed from January 1, 2016, through April 30, 2016. Main Outcomes and Measures: The multivariate Cox proportional hazards regression model was used to determine the clinical or pathologic factors associated with 5-year disease-specific survival (DSS), and these factors were assigned integer points to create a new staging category. The monotonicity and discriminatory ability of the pathologic TNM staging and new staging category were evaluated with the linear trend χ2 test, Akaike information criterion, and Harrell C statistic. Results: In total, 396 patients who underwent major surgery with curative intent for OSCC with or without adjuvant therapy were included in this study (mean [SD] age, 53 [11] years; 367 men [92.7%] and 29 women [7.3%]). Perineural invasion (adjusted hazard ratio [aHR], 1.74; 95% CI, 1.23-2.46), high NLR (aHR, 1.60; 95% CI, 1.11-2.30), advanced pT (T3 + T4) classification (aHR, 1.59; 95% CI, 1.13-2.25), and advanced pN (N2) classification (aHR, 3.96; 95% CI, 2.78-5.63) were independent prognostic survival factors. The ß coefficients from the Cox proportional hazards regression model were used to develop an integer-based weighted point system (perineural invasion, score of 1; NLR, score of 1; advanced pT, score of 1; and advanced pN, score of 3). The summations of these risk scores were stratified for the new staging category as follows: new stage I, score of 0; new stage II, score of 1; new stage III, score of 2 or 3; and new stage IV, score of 4 to 6. Compared with the American Joint Committee on Cancer staging category, this new staging category provided better monotonicity with a higher linear trend χ2 value (106 vs 49), better discriminatory ability with smaller Akaike information criterion (1497 vs 1533), and greater Harrell C statistic (0.73 vs 0.69) for 5-year DSS. The results remained robust after adjusting other risk factors. Conclusions and Relevance: In this study, new staging category had better DSS discriminatory ability and could help to identify high-risk patients for intense adjuvant therapy.
Asunto(s)
Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Neoplasias de la Boca/mortalidad , Neoplasias de la Boca/patología , Adulto , Anciano , Carcinoma de Células Escamosas/sangre , Terapia Combinada , Femenino , Humanos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/sangre , Estadificación de Neoplasias , Neutrófilos , Pronóstico , Modelos de Riesgos Proporcionales , Estudios RetrospectivosRESUMEN
OBJECTIVES: To review cases of peritonsillar abscess and investigate the initial clinical factors that may influence the duration of hospitalization. To determine the predictive factors of prolonged hospital stay in adult patients with peritonsillar abscess. METHODS: Subjects were adults hospitalized with peritonsillar abscess. We retrospectively reviewed 377 medical records from 1990 to 2013 in a tertiary medical center in southern Taiwan. The association between clinical characteristics and the length of hospital stay was analyzed with independent t-test, univariate linear regression and multiple linear regression analysis. RESULTS: The mean duration of hospitalization was 6.2±6.0 days. With univariate linear regression, a prolonged hospital stay was associated with several variables, including female gender, older ages, nonsmoking status, diabetes mellitus, hypertension, band forms in white blood cell (WBC) counts, and lower hemoglobin levels. With multiple linear regression analysis, four independent predictors of hospital stay were noted: years of age (P<0.001), history of diabetes mellitus (P<0.001), ratio of band form WBC (P<0.001), and hemoglobin levels (P<0.001). CONCLUSION: In adult patients with peritonsillar abscess, older ages, history of diabetes mellitus, band forms in WBC counts and lower hemoglobin levels were independent predictors of longer hospitalization.
RESUMEN
Epidemiological studies based on the "hygiene hypothesis" declare that the level of childhood exposure to environmental microbial products is inversely related to the incidence of allergic diseases in later life. Multiple types of immune cell-mediated immune regulation networks support the hygiene hypothesis. Epithelial cells are the first line of response to microbial products in the environment and bridge the innate and adaptive immune systems; however, their role in the hygiene hypothesis is unknown. To demonstrate the hygiene hypothesis in airway epithelial cells, we examined the effect of lipopolysaccharide (LPS; toll-like receptor 4 ligand) on the expression of the proallergic cytokines thymic stromal lymphopoietin (TSLP) and interleukin 33 (IL33) in H292 cells (pulmonary mucoepidermoid carcinoma cells). Stimulation with the TLR ligand polyI:C and human parechovirus type 1 (HPeV1) but not LPS-induced TSLP and IL33 through interferon regulatory factor 3 (IRF3) and NF-κB activity, which was further validated by using inhibitors (dexamethasone and Bay 11-7082) and short hairpin RNA-mediated gene knockdown. Importantly, polyI:C and HPeV1-stimulated TSLP and IL33 induction was reduced by LPS treatment by attenuating TANK-binding kinase 1, IRF3, and NF-κB activation. Interestingly, the basal mRNA levels of TLR signaling proteins were downregulated with long-term LPS treatment of H292 cells, which suggests that such long-term exposure modulates the expression of innate immunity signaling molecules in airway epithelial cells to mitigate the allergic response. In contrast to the effects of LPS treatment, the alarmin high-mobility group protein B1 acts in synergy with polyI:C to promote TSLP and IL33 expression. Our data support part of the hygiene hypothesis in airway epithelia cells in vitro. In addition to therapeutic targeting of TSLP and IL33, local application of non-pathogenic LPS may be a rational strategy to prevent allergies.