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BACKGROUND: The Delphi consensus identified 8 symptoms and 8 consequences as the highest priorities for defining low anterior resection syndrome. OBJECTIVE: To describe an exploratory scoring instrument correlating the Delphi consensus on low anterior resection syndrome with functional and quality-of-life scores following intersphincteric resection for ultralow rectal cancer. DESIGN: This was a prospective pilot study. In accordance with the Wexner incontinence score, 5 frequency responses ranging from never (score 0) to always (score 4) were used to measure the severity of symptom- and consequence-specific variables. SETTINGS: Colorectal surgery referral center. PATIENTS: Among 161 eligible patients, 137 participants (85%) completed an electronic self-assessment survey regarding function and quality of life at scheduled follow-up, including 3 to 6, 12, and ≥24 months after ileostomy reversal. MAIN OUTCOME MEASURES: Outcome measures included patient-reported severity of the identified priorities, and their correlation with condition-specific quality of life. RESULTS: The most frequent symptom and consequence were "emptying difficulties" and "dissatisfaction with the bowels," respectively. Aside from "emptying difficulties," the proportions of negative symptom domains increased after reversal. In particular, neither the frequency responses nor the severity scores of "emptying difficulties" differed between groups. The percentages of "always" selection for consequence domains improved at 12-month follow-up, whereas a higher rate was observed at 24 months, except for "toilet dependence" and "dissatisfaction with the bowels." We found significant improvements in the summary score of the Fecal Incontinence Quality-of-Life Scale ( p = 0.04) and our exploratory instrument ( p = 0.009) but not in functional scores measured by traditional questionnaires. Furthermore, the condition-specific quality of life strongly correlated with the Delphi consensus severity score ( rs = -0.73). LIMITATIONS: Single-institution data and limited sample size. CONCLUSIONS: The important priorities identified by the Delphi consensus might enable a comprehensive overview and a better assessment of low anterior resection syndrome after intersphincteric resection. See Video Abstract . EVALE LA GRAVEDAD DEL SNDROME DE RESECCIN ANTERIOR BAJA DESPUS DE LA RESECCIN INTERESFINTRICA PARA EL CNCER DE RECTO ULTRABAJO UN ESTUDIO PILOTO QUE UTILIZA UN INSTRUMENTO EXPLORATORIO: ANTECEDENTES:El consenso Delphi identificó ocho síntomas y ocho consecuencias como las máximas prioridades para definir el síndrome de resección anterior baja.OBJETIVO:Describir un instrumento de puntuación exploratorio que correlaciona el consenso Delphi sobre el síndrome de resección anterior baja con puntuaciones funcionales y de calidad de vida después de la resección interesfinteriana para el cáncer de recto ultrabajo.DISEÑO:Este fue un estudio piloto prospectivo. De acuerdo con la puntuación de incontinencia de Wexner, se utilizaron cinco respuestas de frecuencia que van desde nunca (puntuación 0) hasta siempre (puntuación 4) para medir la gravedad de las variables específicas de los síntomas y las consecuencias.AJUSTES:Centro de referencia de cirugía colorrectal.PACIENTES:Entre 161 pacientes elegibles, 137 (85%) participantes completaron una encuesta electrónica de autoevaluación sobre la función y la calidad de vida en el seguimiento programado, incluidos 3 a 6, 12 y ≥ 24 meses después de la reversión de la ileostomía.MEDIDAS PRINCIPALES DE RESULTADO:Las medidas de resultado incluyeron la gravedad de estas prioridades informada por los pacientes, así como su correlación con la calidad de vida específica de la afección.RESULTADOS:El síntoma y la consecuencia más frecuentes fueron "dificultades para vaciar" e "insatisfacción con las deposiciones", respectivamente. Aparte de las "dificultades de vaciado", las proporciones de dominios de síntomas negativos aumentaron después de la reversión. En particular, tanto las respuestas de frecuencia como las puntuaciones de gravedad de las "dificultades para vaciar" no difirieron entre los grupos. Los porcentajes de "opción siempre" para los dominios de consecuencias mejoraron a los 12 meses de seguimiento, mientras que se observó una tasa más alta a los 24 meses después, excepto para "dependencia del baño" e "insatisfacción con los intestinos". Encontramos mejoras significativas en la puntuación resumida de la Escala de calidad de vida de incontinencia fecal ( p = 0,04) y nuestro instrumento exploratorio ( p = 0,009), pero no en las puntuaciones funcionales medidas con los cuestionarios tradicionales. Además, la calidad de vida específica de la condición se correlacionó fuertemente con la puntuación de gravedad del consenso Delphi (rs = -0,73).LIMITACIONES:Datos de una sola institución y tamaño de muestra limitado.CONCLUSIONES:Las importantes prioridades identificadas por el consenso Delphi podrían permitir una visión global y una mejor evaluación del síndrome de resección anterior baja después de la resección interesfintérica. (Traducción-Dr. Yesenia Rojas-Khalil ).
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Neoplasias Retais , Humanos , Neoplasias Retais/cirurgia , Síndrome de Ressecção Anterior Baixa , Projetos Piloto , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Qualidade de Vida , Estudos RetrospectivosRESUMO
BACKGROUND: Fried dough sticks, widely enjoyed in southeast Asia, are made by frying a mixture of wheat flour and water at high-temperature. With the move towards industrial production, there is an increasing demand for healthier versions. Understanding the key properties of fried dough sticks and how the ingredients interact is crucial for meeting these health-focused consumer preferences. RESULTS: In this study, the connections between the dough's rheological and thermal properties, alongside the interactions between gluten proteins and the oil content in fried dough sticks, were examined and analyzed at varying gliadin to glutenin mass ratios (Gli/Glu). The results indicated that a general decrease in the viscoelastic properties of the dough was associated with an increase in the Gli/Glu ratio. Furthermore, a heightened concentration of gliadin was observed to augment the mass loss of gluten proteins, thereby engendering a spatially sparse network structure. Additionally, this excessive presence of gliadin precipitated the thermal instability within the dough, necessitating an augmented chemical force to preserve the stability of the gluten network structure. CONCLUSION: At the Gli/Glu ratio of 5:5, the gluten protein exhibited enhanced thermal stability and minimal mass loss. At this specific ratio, the gluten network was characterized by a comparatively high prevalence of extended gluten films and short-chain structures, which resulted in the production of fried dough sticks possessing minimal structural oil content. The study provided a theoretical basis for identifying the Gli/Glu ratio as an effective approach to modulate the oil content in fried dough sticks. © 2024 Society of Chemical Industry.
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BACKGROUND: Intersphincteric resection is the ultimate sphincter-preserving surgical technique for ultralow rectal cancer, but quality-of-life changes after surgery remain unclear. It is also unknown which questionnaire has better associations with functional results for capturing clinical variation in quality of life. OBJECTIVE: This study aimed to assess change in the quality of life and its correlation with functional outcomes among patients undergoing intersphincteric resection for ultralow rectal cancer. DESIGN: This was a prospective, observational, single-center study. SETTINGS: Colorectal surgery referral center. PATIENTS: Patients with ultralow rectal cancer who underwent intersphincteric resection were included. MAIN OUTCOME MEASURES: The primary outcomes were quality-of-life and functional results at 3 to 6, 12, and 24 months after ileostomy closure using validated questionnaires. The secondary outcome was the relationship between quality of life and neorectal function. RESULTS: A total of 102 patients (62.7% men) completed follow-up surveys. Wexner incontinence score and Kirwan's incontinence score significantly improved at 12 months after ileostomy reversal, but such improvement in low anterior resection syndrome score was proved until 24 months later ( p = 0.01). Condition-specific quality-of-life domains improved over time, with significant changes in lifestyle ( p = 0.02) and coping/behavior ( p = 0.01), as well as the summary score of Fecal Incontinence Quality of Life ( p = 0.02) and visual analog scale score ( p < 0.001). Among health-related quality-of-life domains, the subscale scores did not differ significantly. The functional systems scores were significantly correlated with all the domains of condition-specific quality-of-life but only a few health-related quality-of-life domains. Only weak to moderate associations with the functional outcomes were observed for both quality-of-life questionnaires. LIMITATIONS: Single-center data and limited sample size. CONCLUSIONS: Although low anterior resection syndrome persists for years after intersphincteric resection, condition-specific quality of life and functional outcomes improve over time. Compared to health-related quality-of-life questionnaires, condition-specific quality-of-life instruments might be preferable to evaluate changes in quality-of-life after surgery. See Video Abstract at http://links.lww.com/DCR/C130 . CALIDAD DE VIDA Y RESULTADOS FUNCIONALES DESPUS DE UNA RESECCIN INTERESFINTRICA EN CASO DE CNCER RECTAL ULTRABAJO ESTUDIO PROSPECTIVO OBSERVACIONAL: ANTECEDENTES:La resección inter-esfintérica es la última técnica quirúrgica conservadora de esfínteres en casos de cáncer rectal ultrabajo, pero los cambios en la calidad de vida después de la cirugía siguen sin estar claros. Se desconoce también, qué tipo de cuestionario tiene mejor asociación con los resultados funcionales para así captar las variaciones clínicas en la calidad de vida.OBJETIVO:Evaluar el cambio en la calidad de vida y su correlación con los resultados funcionales durante el período postoperatorio en pacientes sometidos a resección interesfintérica por cáncer de recto ultrabajo.DISEÑO:Estudio prospectivo, observacional y de un solo centro.AJUSTES:Centro de referencia de cirugía colorrectal.PACIENTES:Se incluyeron pacientes con cáncer de recto ultra bajo que se sometieron a resección interesfintérica con el cierre de la ileostomía.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue la calidad de vida y los resultados funcionales a los 3-6, 12 y 24 meses después del cierre de la ileostomía utilizando cuestionarios validados. El resultado secundario fue la relación entre la calidad de vida y la función del néorecto.RESULTADOS:Un total de 102 pacientes (62,7% hombres) completaron las encuestas de seguimiento. La puntuación de incontinencia de Wexner y la puntuación de incontinencia de Kirwan mejoraron significativamente a los 12 meses después del cierre de la ileostomía, pero dicha mejoría en la puntuación del síndrome de resección anterior baja se demostró solo hasta 24 meses después ( p = 0,01). Las condiciones en el dominio de la calidad de vida específicos mejoraron con el tiempo, con cambios significativos en el estilo de vida ( p = 0,02) y el afrontamiento/comportamiento ( p = 0,01), así como la puntuación general de la calidad de vida y de la incontinencia fecal ( p = 0,02), puntuación de la escala analógica visual ( p < 0,001). Entre los dominios de la calidad de vida relacionada con la salud, las puntuaciones de las sub-escalas no difirieron significativamente. Las puntuaciones de los sistemas funcionales se correlacionaron significativamente con todos los dominios de la calidad de vida específica de la nueva condición, pero solo con pocos dominios de calidad de vida relacionados con la salud. Solo se observaron asociaciones débiles a moderadas con los resultados funcionales para ambos cuestionarios de calidad de vida.LIMITACIONES:Datos de un solo centro y tamaño de muestra limitado.CONCLUSIONES:Aunque el síndrome de resección anterior baja persiste durante años después de la resección interesfintérica, la calidad de vida específica de la nueva condición y los resultados funcionales mejoran con el tiempo. En comparación con los cuestionarios de calidad de vida relacionados con la salud, los instrumentos de calidad de vida específicos de la nueva condición pueden ser preferibles para evaluar los cambios en la calidad de vida después de la cirugía. Consulte Video Resumen en http://links.lww.com/DCR/C130 . (Traducción-Dr. Xavier Delgadillo ).
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Incontinência Fecal , Neoplasias Retais , Masculino , Humanos , Feminino , Neoplasias Retais/cirurgia , Complicações Pós-Operatórias/epidemiologia , Qualidade de Vida , Estudos Prospectivos , Reto/cirurgia , Incontinência Fecal/epidemiologia , Incontinência Fecal/etiologia , Síndrome de Ressecção Anterior Baixa , Canal Anal/cirurgiaRESUMO
Interventions to teach protective behaviors may be differentially effective within an adolescent population. Identifying the characteristics of youth who are less likely to respond to an intervention can guide program modifications to improve its effectiveness. Using comprehensive longitudinal data on adolescent risk behaviors, perceptions, sensation-seeking, peer and family influence, and neighborhood risk factors from 2564 grade 10-12 students in The Bahamas, this study employs machine learning approaches (support vector machines, logistic regression, decision tree, and random forest) to identify important predictors of non-responsiveness for precision prevention. We used 80% of the data to train the models and the rest for model testing. Among different machine learning algorithms, the random forest model using longitudinal data and the Boruta feature selection approach predicted intervention non-responsiveness best, achieving sensitivity of 85.4%, specificity of 78.4% and AUROC of 0.93 on the training data, and sensitivity of 84.3%, specificity of 67.1%, and AUROC of 0.85 on the test data. Key predictors include self-efficacy, perceived response cost, parent monitoring, vulnerability, response efficacy, HIV/AIDS knowledge, communication about condom use, and severity of HIV/STI. Machine learning can yield powerful predictive models to identify adolescents who are unlikely to respond to an intervention. Such models can guide the development of alternative strategies that may be more effective with intervention non-responders.
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Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Infecções Sexualmente Transmissíveis , Humanos , Adolescente , Síndrome da Imunodeficiência Adquirida/prevenção & controle , Infecções por HIV/diagnóstico , Infecções por HIV/prevenção & controle , Infecções por HIV/epidemiologia , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/prevenção & controle , Sexo Seguro , Aprendizado de MáquinaRESUMO
PURPOSE OF REVIEW: Three biologics targeting type 2 inflammation have been approved for the treatment of severe and uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP). Nevertheless, around 40-60% of patients do not respond well to these biological treatments. Selecting appropriate patients is crucial to improve treatment outcome of biologics. This review summarizes the literature data on type 2 biomarkers, with a specific focus on the indication to biologics for severe CRSwNP. RECENT FINDINGS: No consensus has been reached on how to define mucosal type 2 inflammation in CRSwNP. Clinical markers (e.g., 22-item Sino-nasal Outcome Test (SNOT-22) score, Lund-Mackay CT score (LMS), ethmoid/maxillary sinus CT score, and CT-radiomics), nasal secretion biomarkers (e.g., eosinophil cationic protein and interleukin-5), blood and nasal cytology eosinophil counts, and nasal swab eosinophil peroxidase activity have been reported to be associated with type 2 inflammation in CRSwNP. The time duration since the last surgery, SNOT-22 score at 1 week of treatment, and baseline serum osteoprotegerin levels might indicate the response to dupilumab. LMS and asthma control test scores were found to have moderate predictive value for acceptable improvement after 24-week treatment of omalizumab. High blood eosinophil levels at baseline were associated with treatment response to mepolizumab and benralizumab. Although several clinical and biological markers might be associated with type 2 inflammation and response to biologics in patients with CRSwNP, their validity requires further investigation. Identifying clinically applicable biomarkers for biologic treatment holds significant promise for advancing personalized approaches to biologics and optimizing treatment outcomes for patients with CRSwNP.
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Produtos Biológicos , Pólipos Nasais , Rinite , Sinusite , Humanos , Rinite/diagnóstico , Rinite/tratamento farmacológico , Rinite/complicações , Inflamação , Sinusite/diagnóstico , Sinusite/tratamento farmacológico , Sinusite/complicações , Biomarcadores , Pólipos Nasais/tratamento farmacológico , Pólipos Nasais/complicações , Produtos Biológicos/uso terapêutico , Doença CrônicaRESUMO
INTRODUCTION: We used a longitudinal cohort of US adults who were current or former smokers to explore how three participant-reported factors-general stress, coronavirus disease of 2019 (COVID-19) distress, and perceived risk of complications from COVID-19 related to smoking-were associated with changes in smoking status. METHODS: Smoking status was assessed at three time points. Timepoint 1 status was assessed at a prior study completion (2018-2020). Timepoint 2 (start of the pandemic), and Timepoint 3 (early phase of the pandemic) statuses were assessed using an additional survey in 2020. After classifying participants into eight groups per these time points, we compared the means of participant-reported factors and used a linear regression model to adjust for covariates. RESULTS: Participants (n = 392) were mostly female (73.9%) and non-Hispanic White (70.1%). Between Timepoints 2 and 3, abstinence rates decreased by 11%, and 40% of participants reported a smoking status change. Among those reporting a change and the highest general stress levels, newly abstinent participants had higher perceived risk of complications from COVID-19 related to smoking than those who relapsed during pandemic (mean (SD): 14.2 (3.3) vs. 12.6 (3.8)). Compared to participants who sustained smoking, those who sustained abstinence, on average, scored 1.94 less on the general stress scale (ßeta Coefficient (ß): -1.94, p-value < .01) and 1.37 more on the perceived risk of complications from COVID-19 related to smoking scale (ß: 1.37, p-value .02). CONCLUSIONS: Decreased abstinence rates are concerning. Patterns of reported factors were as expected for individuals who sustained their smoking behavior but not for those who changed. IMPLICATIONS: We observed an increase in smoking rates during the COVID-19 pandemic. In exploring how combinations of general stress levels, COVID-19 distress levels, and perceived risk of complications from COVID-19 related to smoking were associated with changes in smoking, we observed expected patterns of these factors among individuals who sustained abstinence or smoking. Among individuals who changed smoking status and reported high stress levels, those who reported a higher perceived risk of complications from COVID-19 related to smoking abstained from smoking. In contrast, those who reported a lower perceived risk of complications from COVID-19 related to smoking, started smoking. An intersectional perspective may be needed to understand smokers' pandemic-related behavior changes.
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COVID-19 , Abandono do Hábito de Fumar , Adulto , Humanos , Feminino , Masculino , Pandemias , Fumantes , COVID-19/epidemiologia , Fumar/epidemiologiaRESUMO
Clinical documentation in electronic health records contains crucial narratives and details about patients and their care. Natural language processing (NLP) can unlock the information conveyed in clinical notes and reports, and thus plays a critical role in real-world studies. The NLP Working Group at the Observational Health Data Sciences and Informatics (OHDSI) consortium was established to develop methods and tools to promote the use of textual data and NLP in real-world observational studies. In this paper, we describe a framework for representing and utilizing textual data in real-world evidence generation, including representations of information from clinical text in the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM), the workflow and tools that were developed to extract, transform and load (ETL) data from clinical notes into tables in OMOP CDM, as well as current applications and specific use cases of the proposed OHDSI NLP solution at large consortia and individual institutions with English textual data. Challenges faced and lessons learned during the process are also discussed to provide valuable insights for researchers who are planning to implement NLP solutions in real-world studies.
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Ciência de Dados , Informática Médica , Humanos , Registros Eletrônicos de Saúde , Processamento de Linguagem Natural , NarraçãoRESUMO
PURPOSE: To determine whether anastomotic leakage (AL) following intersphincteric resection (ISR) for ultralow rectal cancer (uLRC) is associated with long-term negative outcomes. METHODS: Between June 2011 and January 2022, 236 consecutive patients who underwent ISR with diverting ileostomy for uLRC were included. The primary outcome was long-term clinical consequences of AL, including chronic stricture, stoma reversal, and oncological and functional results. RESULTS: Forty-one (17.4%) patients developed symptomatic AL, whereas only two (0.8%) required re-laparotomy due to severe leakage. Patients with leaks had a significantly increased incidence of chronic stricture (29.3% vs. 8.7%, P = 0.001) and stoma non-reversal (34.1% vs. 4.6%, P < 0.0001) than controls. The severe consequences were particularly common in patients with anastomotic separation, resulting in 60% of those presenting with chronic stricture and 50% ending up with stoma non-reversal. After a median follow-up of 59 (range, 7-139) months, AL did not compromise long-term oncological outcomes, including tumor recurrence (9.8% vs. 5.6%, P = 0.3), 5-year disease-free, and overall survival (73.4% vs. 74.8% and 85.1% vs. 85.4%, P = 0.56 and P = 0.55). A total of 149 patients with bowel continuity who completed self-assessment questionnaires were enrolled for functional evaluation. The median follow-up was 24 (range, 12-94) months after ileostomy reversal, and functional results were comparable between patients with and without leaks. CONCLUSION: AL is an unfortunate reality for patients who underwent ISR for uLRC, but the rate of severe leakage is limited. Leaks contribute to possible adverse impacts on chronic stricture and stoma non-reversal, especially for patients with anastomotic separation. However, long-term oncological and functional results may not be compromised. TRIAL REGISTRATION: Chictr.org.cn identifier: ChiCTR-ONC-15007506 and ChiCTR2100051614.
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Fístula Anastomótica , Neoplasias Retais , Humanos , Fístula Anastomótica/epidemiologia , Fístula Anastomótica/etiologia , Constrição Patológica , Canal Anal/cirurgia , Recidiva Local de Neoplasia/patologia , Neoplasias Retais/cirurgia , Neoplasias Retais/patologia , Anastomose Cirúrgica/efeitos adversos , Estudos RetrospectivosRESUMO
BACKGROUND: There is a need to evaluate how the choice of time interval contributes to the lack of consistency of SDoH variables that appear as important to COVID-19 disease burden within an analysis for both case counts and death counts. METHODS: This study identified SDoH variables associated with U.S county-level COVID-19 cumulative case and death incidence for six different periods: the first 30, 60, 90, 120, 150, and 180 days since each county had COVID-19 one case per 10,000 residents. The set of SDoH variables were in the following domains: resource deprivation, access to care/health resources, population characteristics, traveling behavior, vulnerable populations, and health status. A generalized variance inflation factor (GVIF) analysis was used to identify variables with high multicollinearity. For each dependent variable, a separate model was built for each of the time periods. We used a mixed-effect generalized linear modeling of counts normalized per 100,000 population using negative binomial regression. We performed a Kolmogorov-Smirnov goodness of fit test, an outlier test, and a dispersion test for each model. Sensitivity analysis included altering the county start date to the day each county reached 10 COVID-19 cases per 10,000. RESULTS: Ninety-seven percent (3059/3140) of the counties were represented in the final analysis. Six features proved important for both the main and sensitivity analysis: adults-with-college-degree, days-sheltering-in-place-at-start, prior-seven-day-median-time-home, percent-black, percent-foreign-born, over-65-years-of-age, black-white-segregation, and days-since-pandemic-start. These variables belonged to the following categories: COVID-19 related, vulnerable populations, and population characteristics. Our diagnostic results show that across our outcomes, the models of the shorter time periods (30 days, 60 days, and 900 days) have a better fit. CONCLUSION: Our findings demonstrate that the set of SDoH features that are significant for COVID-19 outcomes varies based on the time from the start date of the pandemic and when COVID-19 was present in a county. These results could assist researchers with variable selection and inform decision makers when creating public health policy.
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COVID-19 , Segregação Social , Adulto , COVID-19/epidemiologia , Humanos , Políticas , SARS-CoV-2 , Determinantes Sociais da Saúde , Estados Unidos/epidemiologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: DaiTongXiao (DTX) is a traditional Chinese Dai folk formulation utilized for gouty arthritis treatment, with substantial evidence supporting its anti-inflammatory properties. The NLRP3 inflammasome disorder is tightly linked to the development of many inflammatory diseases. AIM OF THE STUDY: To elucidate the therapeutic efficacy of DTX in gouty arthritis and reveal its potential underlying mechanism. MATERIALS AND METHODS: The primary active constituents in DTX were determined through ultraviolet spectrophotometry and gas chromatography. Rats underwent induction with monosodium urate (MSU), followed by treatment of J774A.1 cells with adenosine triphosphate (ATP) activation and lipopolysaccharide (LPS) induction and the subsequent culture in Dulbecco's modified Eagle's medium. The degree of foot joint swelling in rats was assessed, and ankle joints were evaluated through H&E staining. Enzyme-linked immunosorbent assay was performed to measure the levels of interleukin (IL)-1ß, IL-6, IL-8, and tumor necrosis factor (TNF)-α in both serum and cells. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to determine the relative mRNA expression levels of NLRP3, ASC, Caspase-1, and NF-κB in J774A.1 macrophages. The expression of NLRP3, ASC, Caspase-1, and NF-κB was examined by western blotting. RESULTS: DTX could alleviate MSU-induced joint swelling in rats, as evidenced by a reduction in joint inflammation. Moreover, DTX effectively enhanced the survival rate of J774A.1 cells following LPS induction and ATP activation. Furthermore, DTX significantly reduced IL-1ß, IL-6, IL-8, and TNF-α levels in both cell culture medium and rat serum. RT-PCR results revealed that DTX notably downregulated the mRNA expression levels of NLRP3, ASC, Caspase-1, and NF-κB in J774A.1 cells. Additionally, DTX downregulated NLRP3, ASC, NF-κB, and Caspase-1 expression in the joint tissue. CONCLUSIONS: DTX exerts a significant anti-gouty arthritis effect, with its mechanism being tightly linked to the NLRP3 inflammatory signaling pathway. This pathway may be modulated by inhibiting IL-1ß differentiation and maturation by downregulating NLRP3, ASC, Caspase-1, and NF-κB protein expression. This, in turn, leads to a reduction in the release of IL-6, IL-8, and TNF-α, ultimately impeding gouty arthritis progression.
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Artrite Gotosa , Ratos , Animais , Artrite Gotosa/induzido quimicamente , Artrite Gotosa/tratamento farmacológico , Artrite Gotosa/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6 , Lipopolissacarídeos , Interleucina-8 , Transdução de Sinais , Inflamassomos/metabolismo , Ácido Úrico , Caspase 1/metabolismo , Edema , Trifosfato de Adenosina , RNA MensageiroRESUMO
Background: Malignant cerebral edema (MCE), a potential complication following endovascular thrombectomy (EVT) in the treatment of acute ischemic stroke (AIS), can result in significant disability and mortality. This study aimed to develop a nomogram model based on the hyperattenuated imaging marker (HIM), characterized by hyperattenuation on head noncontrast computed tomography (CT) immediately after thrombectomy, to predict MCE in patients receiving EVT. Methods: In this retrospective cohort study, we selected 151 patients with anterior circulation large-vessel occlusion who received endovascular treatment. The patients were randomly allocated into training (n=121) and test (n=30) cohorts. HIM was used to extract radiomics characteristics. Conventional clinical and radiological features associated with MCE were also extracted. A model based on extreme gradient boosting (XGBoost) machine learning using fivefold cross-validation was employed to acquire radiomics and clinical features. Based on HIM, clinical and radiological signatures were used to construct a prediction nomogram for MCE. Subsequently, the signatures were merged through logistic regression (LR) analysis in order to create a comprehensive clinical radiomics nomogram. Results: A total of 28 patients out of 151 (18.54%) developed MCE. The analysis of the receiver operating characteristic curve indicated an area under the curve (AUC) of 0.999 for the prediction of MCE in the training group and an AUC of 0.938 in the test group. The clinical and radiomics nomogram together showed the highest accuracy in predicting outcomes in both the training and test groups. Conclusions: The novel nomogram, which combines clinical manifestations and imaging findings based on postinterventional HIM, may serve as a predictor for MCE in patients experiencing AIS after EVT.
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This study aimed to investigate the potential mechanisms involved in the therapeutic effects of daitongxiao (DTX) on hyperuricemia (HUA). DTX was administered to two animal models of HUA via gavage feeding: HUA quail model (a uricotelic animal with urate oxidase deficiency), treated continuously for 35 days post-HUA induction, and HUA rats (an animal with active urate oxidase), treated continuously for 28 days post-HUA induction. HUA was induced in quail by administering a solution of sterile dry yeast powder via gavage feeding, while in rats, it was induced by intragastric gavage feeding of a solution of adenine and ethambutol hydrochloride. DTX improved overall health; increased bodyweight; reduced renal index, serum urate levels, serum xanthine oxidase activity, blood urea nitrogen, and creatinine; and enhanced urinary and fecal uric acid (UA) excretion in these two animal models. The results of hematoxylin and eosin and hexamine silver staining of kidney sections revealed that DTX significantly mitigated HUA-induced renal structural damage and inflammatory response. The results of quantitative real-time polymerase chain reaction, Western blotting, and immunofluorescence analyses revealed that DTX downregulated the renal expression levels of glucose transporter 9 (GLUT9) and upregulated the renal expression levels of organic anion transporters (OAT1 and OAT3) in both HUA models. Thus, the findings of this study suggest that DTX suppresses the progression of HUA by modulating the expression of the UA transporter group members.
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The fall armyworm (FAW) is a serious agricultural pest and has developed resistance to multiple insecticides. It is necessary to introduce novel insecticide(s) for controlling FAW. Isocycloseram is a completely novel isoxazoline insecticide. However, its activity and mode of action against FAW have not been reported. In this study, isocycloseram exhibited a higher insecticidal activity (LC50 = 0.26 mg/kg) than fipronil (LC50 = 7.72 mg/kg) against FAW. The median inhibitory concentration (IC50) of isocycloseram (IC50 = 8.52 nM) was almost equal to that of the desmethyl-broflanilide (IC50 = 7.32 nM) to the SfrRDL1 receptor. The IC50 of isocycloseram to the SfrRDL2 receptor was 11.13 nM, which was obviously less than that of desmethyl-broflanilide, dieldrin, fipronil, fluxametamide. Compared with the SfrRDL2 receptor, the SfrRDL1 receptor exhibited higher sensitivity to GABAergic insecticides. The recombinant SfrGluCl receptor was successfully stimulated by l-glutamate; however, the currents were low and weakly inhibited by isocycloseram at 10 µM. In conclusion, our results provided the theoretical basis for usage of GABAergic insecticides for controlling FAW.
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Proteínas de Insetos , Inseticidas , Animais , Inseticidas/farmacologia , Inseticidas/química , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Spodoptera/efeitos dos fármacos , Isoxazóis/farmacologia , Pirazóis/farmacologiaRESUMO
Background: According to the World Health Organization (WHO), healthy aging is the process of developing and maintaining the functional capacity for health in old age. A rapidly growing number of research studies on healthy aging have been conducted worldwide. The purpose of this research work is to explore global scientific landscape of healthy aging research over the last 22 years. Methods: Scientific publications on healthy aging from January 1, 2000 to October 11, 2022 were retrieved from the Web of Science Core Collection (WoSCC) on October 11, 2022. A total of 6420 publications were included in the scientometric analysis. VOSviewer (1.6.18) was used to conduct scientometric and visualized analysis. Results: The publication growth rate was 35.68 from 2000 to 2021. The United States of America (USA) led in both productivity and citations. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA was prominent in terms of both the highest citation count and the highest average citation count. The National Institute on Aging (NIA) and Evans, Michele K. were the most influential organization and author, respectively. Research hotspots in healthy aging were identified based on the co-occurrence analysis of keywords: (1) physical activity and mental health of older adults; (2) diseases impacting the health and lifespan of older adults; and (3) neuroscience. Our analysis indicates that gut microbiota, loneliness, frailty, mitochondria and resilience were the emerging themes in healthy aging research. Conclusions: The quantity of annual publications on healthy aging has rapidly increased over the past 22 years, especially during 2018-2021. This analysis identified the status, trends, hot topics, and frontiers of healthy aging research. These findings will help researchers quickly understand the global representation of healthy aging research, influence resource dissemination, promote international collaborations, guide policy formulation, and improve health services for older adults.
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The present review expounds the advancements in the application and mechanisms of flavonoids in gouty arthritis, highlighting their significance in managing the disease. Gouty arthritis is among the most common and severe inflammatory diseases, caused by hyperuricemia and the deposition of sodium urate crystals in the joints and surrounding tissues, posing a serious threat to human life and health. Flavonoids, extracted from various herbs, have attracted significant attention due to their efficacy in improving gouty arthritis. The present study systematically reviews the in vivo studies and in vitro animal studies on flavonoids from herbal medicines for the treatment of gouty arthritis that have been previously published in the PubMed, ScienceDirect, Google Scholar and China National Knowledge Infrastructure databases between 2000 and 2023. The review of the literature indicated that flavonoids can improve gouty arthritis through multiple mechanisms. These include lowering xanthine oxidase activity, inhibiting uric acid (UA) synthesis, regulating UA transporters to promote UA excretion, reducing the inflammatory response and improving oxidative stress. These mechanisms predominantly involve regulating the NODlike receptor 3 inflammasome, the Tolllike receptor 4/myeloid differentiation factor 88/nuclear factorκB signaling pathway, and the levels of UA transporter proteins, namely recombinant urate transporter 1, glucose transporter 9, organic anion transporter (OAT)1 and OAT3. Various flavonoids used in traditional Chinese medicine hold therapeutic promise for gouty arthritis and are anticipated to pave the way for novel pharmaceuticals and clinical applications.
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Artrite Gotosa , Flavonoides , Ácido Úrico , Artrite Gotosa/tratamento farmacológico , Artrite Gotosa/metabolismo , Humanos , Flavonoides/uso terapêutico , Flavonoides/farmacologia , Flavonoides/química , Animais , Ácido Úrico/metabolismo , Transdução de Sinais/efeitos dos fármacos , Xantina Oxidase/metabolismo , Xantina Oxidase/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Hiperuricemia/tratamento farmacológico , Hiperuricemia/metabolismoRESUMO
Background: The limitations of prostate-specific antigen (PSA) in diagnosing prostate cancer (PCa) necessitate the exploration of novel biomarkers. Recent studies suggest a potential link between coagulation markers, particularly fibrinogen and D-dimer, and PCa. Methods: A retrospective single-center analysis on 466 biopsy-undergone patients was conducted, categorized into PCa and benign prostatic hyperplasia (BPH) groups. Baseline and coagulation parameter levels were analyzed. Utilizing a Mendelian randomization (MR) approach, we investigated the causative relationship between D-dimer and PCa risk. Results: Individuals with PCa, compared with those with BPH, exhibited significantly higher D-dimer levels (P < .001), total PSA (P < .001), and PSA density (P < .001). Fibrinogen levels did not exhibit significant differences (P = .505). The MR analysis suggested a probable causal link between elevated D-dimer levels and an increased risk of PCa (odds ratio: 1.81, 95% confidence interval: 1.48-2.21, P = 7.4 × 10-9). Conclusions: This research highlights D-dimer as a potential biomarker for diagnosing PCa, supported by clinical and MR analyses. The study paves the way for future large-scale, multi-center research to corroborate these findings and further explore the relationship between coagulation markers and PCa mechanisms.
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Blue corona discharges are often generated in thunderclouds penetrating into the stratosphere and are the optical manifestation of narrow bipolar events (NBEs) observed in radio signals. While their production appears to depend on convection, the cause and nature of such discharges are not well known. Here we show the observations by a lightning detection array of unusual amounts of 982 NBEs during a tropical storm on the coastline of China. NBEs of negative polarity are predominantly observed at the cloud top reaching the stratosphere, and positive NBEs are primarily at lower altitudes. We find that the dominant polarity changes with the typical time of development of thunderstorm cells, suggesting that the polarity depends on the phase of the storm cells. Furthermore, we find that the lightning jump of negative NBEs is associated with above-anvil cirrus plumes of ice crystals and water vapor in the lower stratosphere. We propose that variations in updrafts induce changes in the altitude and charge concentrations of the cloud layers, which lead to the polarity transition. Our results have implications for studies of the chemical perturbations of greenhouse gas concentrations by corona discharges at the tropopause.
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ETHNOPHARMACOLOGICAL RELEVANCE: Yajieshaba (YJSB), approved by the Yunnan Provincial Food and Drug Administration in 2008, are known for their anti-inflammatory, antiviral, and pro-apoptotic properties, effectively treating Hepatic fibrosis (HF). However, its mechanism of action remains unclear. AIM OF THE STUDY: The objective of this investigation is to explore how YJSB influences the TGF-ß1/Smad signaling pathway as a strategy for reducing HF. METHODS: The establishment of a HF model in mice involved ligation of the common bile duct, followed by administration of YJSB. Body and liver weights were measured, and the liver index calculated. Serum levels of ALT, AST, ALP, TBA, and TBIL were assessed using colorimetric methods. Additionally, liver homogenates were analyzed for PIIINP, Col-IV, LN, HA, and Hyp, as well as TGF-ß1 activity, using ELISA. Histological analyses of liver sections, stained with H&E, Ag, and Masson's trichrome, were performed to examine inflammation and the accumulation of collagen and reticular fibers. These studies aimed to elucidate the pharmacodynamic effects of YJSB on HF in mice with bile duct obstruction. The target pathways of YJSB were preliminarily identified through immunofluorescence detection of TGF-ß1, P-Smad2L, P-Smad2C, P-Smad3L, P-Smad3C, and Smad4 proteins. In vitro experiments included the induction of hepatic stellate cell (HSC-T6) activation by H2O2. A cell injury model was established for HSC-T6, and the CCK-8 assay was used to determine the optimal YJSB concentration and treatment duration. After pirfenidone (PFD) administration, which inhibits the TGF-ß1/Smad pathway, the effects of YJSB on HSC-T6 cell proliferation were observed. ELISA assays quantified Col-III, α-SMA, and Col-I in cell lysates to assess YJSB's impact on collagen synthesis in HSC-T6 cells. Western blot analysis was performed to assess the protein levels within the TGF-ß1/Smad signaling cascade. RESULTS: In the HF mouse model, administration of YJSB notably augmented the body weight and reduced the liver index. Concurrently, there was an elevation in serum concentrations of ALP, AST, ALT, TBA, and TBIL. Similarly, in the liver homogenates of HF mice, increases were observed in the levels of HA, PIIINP, Col-IV, LN, Hyp, and TGF-ß1. Histological assessments using H&E, Ag, and Masson stains indicated a substantial diminution in liver tissue damage. Through immunofluorescence analysis, it was discerned that YJSB modulated the expression of TGF-ß1, P-Smad2L, P-Smad2C, and P-Smad3L downwards, while elevating P-Smad3C and Smad4 protein expressions. Additional investigations revealed a significant reduction in α-SMA, Col-I, and Col-III levels in cell culture fluids, suggesting a decrease in collagen synthesis and a protective role against cellular damage. Western blot analyses demonstrated that the TGF-ß1/Smad pathway inhibitor, PFD, acted in synergy with YJSB, enhancing its regulatory effects on this pathway, decreasing levels of TGF-ß1, P-Smad2L, P-Smad2C, P-Smad3L, and promoting the expression of P-Smad3C. CONCLUSIONS: YJSB demonstrates a pharmacodynamic effect against HF, enhancing liver functionality and effectively mitigating the damage associated with bile duct obstruction. The proposed action mechanism of YJSB involves modulation of the TGF-ß1/Smad signaling pathway. Research indicates that YJSB might play a role in suppressing the movement, programmed cell death, and activation of HSC-T6, potentially decelerating the advancement of hepatic fibrosis.
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Colestase , Células Estreladas do Fígado , Peróxido de Hidrogênio , Cirrose Hepática , Transdução de Sinais , Fator de Crescimento Transformador beta1 , Animais , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Fator de Crescimento Transformador beta1/metabolismo , Camundongos , Masculino , Peróxido de Hidrogênio/metabolismo , Colestase/metabolismo , Colestase/patologia , Colestase/tratamento farmacológico , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Transdução de Sinais/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Linhagem Celular , Modelos Animais de Doenças , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/metabolismo , Proteínas Smad/metabolismo , Camundongos Endogâmicos C57BL , Proteína Smad2/metabolismoRESUMO
Introduction: Gouty nephropathy (GN) arises from factors like excessive purine intake, metabolic disorders or abnormal synthesis, and uric acid hypersaturation in the blood, leading to urate crystal deposition in kidney tissue. DaiTongXiao (DTX) is a remedy used by the Dai people of China. It shows efficacy in lowering uric acid levels and exhibits anti-inflammatory and kidney-protective properties. Methods: A GN rat model was induced using adenine and potassium oxonate. Following DTX administration, various parameters were assessed in urine, serum, and kidney tissue. Western blot analysis evaluated TLR4/MyD88/NF-κB signaling proteins, while immunofluorescence examined NF-κB nuclear expression. Results: DTX treatment improved kidney morphology, increased body weight, and kidney index and enhanced urinary levels of blood urea nitrogen (Bun), 24-h urinary protein, uric acid (UA), and allantoin in GN rats, reducing UA, Bun, creatinine (Cre), cystatin C (CysC), serum amyloid A (SAA), α1-microglobulin (MG), and ß2-MG in serum analysis. Renal tissue assessments showed decreased xanthine oxidase (XOD), hydroxyproline (Hyp), α-smooth muscle actin (α-SMA), and collage type â £ (COL-â £). Kidney damage severity was notably reduced. DTX lowered serum inflammatory factors like interleukin (IL) -18, tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), transforming growth factor-ß1 (TGF-ß1), and IL-1ß in the rat serum, reducing chemokine monocyte chemoattractant protein-1 (MCP-1) and adhesion factor vascular cell adhesion molecule-1(VCAM-1). Western blotting demonstrated the downregulation of TLR4/MyD88/NF-κB pathway proteins, and immunofluorescence revealed reduced NF-κB expression in renal tissue. Discussion: DTX exhibits significant anti-GN effects by modulating TLR4/MyD88/ NF-κB pathway protein expression, reducing inflammatory factor release, and inhibiting GN progression.