Resveratrol Alleviates Osteoporosis by Promoting Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells via SITR1/PI3K/AKT Pathway / El Resveratrol Alivia la Osteoporosis al Promover la Diferenciación Osteogénica de las Células Madre Mesenquimales de la Médula Ósea a Través de la Vía SITR1/PI3K/AKT

SUMMARY: Senile osteoporosis is mainly caused by reduced osteoblast differentiation and has become the leading cause of fractures in the elderly worldwide. Natural organics are emerging as a potential option for the prevention and treatment of osteoporosis. This study was designed to study the effect of resveratrol on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in osteoporosis mice. A mouse model of osteoporosis was established by subcutaneous injection of dexamethasone and treated with resveratrol administered by gavage. In vivo and in vitro, we used western blot to detect protein expression, and evaluated osteogenic differentiation of BMSCs by detecting the expression of osteogenic differentiation related proteins, calcium deposition, ALP activity and osteocalcin content. Resveratrol treatment significantly increased the body weight of mice, the level of serum Ca2+, 25(OH)D and osteocalcin, ration of bone weight, bone volume/total volume, trabecular thickness, trabecular number, trabecular spacing and cortical thickness in osteoporosis mice. In BMSCs of osteoporosis mice, resveratrol treatment significantly increased the expression of Runx2, osterix (OSX) and osteocalcin (OCN) protein, the level of calcium deposition, ALP activity and osteocalcin content. In addition, resveratrol treatment also significantly increased the expression of SIRT1, p-PI3K / PI3K and p-AKT / AKT in BMSCs of osteoporosis mice. In vitro, resveratrol increased the expression of SIRT1, p-PI3K / PI3K and p-AKT / AKT, Runx2, OSX and OCN protein, the level of calcium deposition, ALP activity and osteocalcin content in BMSCs in a concentration-dependent manner, while SIRT1 knockdown significantly reversed the effect of resveratrol. Resveratrol can attenuate osteoporosis by promoting osteogenic differentiation of bone marrow mesenchymal stem cells, and the mechanism may be related to the regulation of SIRT1/PI3K/AKT pathway.

La osteoporosis senil es causada principalmente por una diferenciación reducida de osteoblastos y se ha convertido en la principal causa de fracturas en las personas mayores en todo el mundo. Los productos orgánicos naturales están surgiendo como una opción potencial para la prevención y el tratamiento de la osteoporosis. Este estudio fue diseñado para estudiar el efecto del resveratrol en la diferenciación osteogénica de las células madre mesenquimales de la médula ósea (BMSC) en ratones con osteoporosis. Se estableció un modelo de osteoporosis en ratones mediante inyección subcutánea de dexametasona y se trató con resveratrol administrado por sonda. In vivo e in vitro, utilizamos Western blot para detectar la expresión de proteínas y evaluamos la diferenciación osteogénica de BMSC detectando la expresión de proteínas relacionadas con la diferenciación osteogénica, la deposición de calcio, la actividad de ALP y el contenido de osteocalcina. El tratamiento con resveratrol aumentó significativamente el peso corporal de los ratones, el nivel sérico de Ca2+, 25(OH)D y osteocalcina, la proporción de peso óseo, el volumen óseo/ volumen total, el espesor trabecular, el número trabecular, el espaciado trabecular y el espesor cortical en ratones con osteoporosis. En BMSC de ratones con osteoporosis, el tratamiento con resveratrol aumentó significativamente la expresión de las proteínas Runx2, osterix (OSX) y osteocalcina (OCN), el nivel de deposición de calcio, la actividad de ALP y el contenido de osteocalcina. Además, el tratamiento con resveratrol también aumentó significativamente la expresión de SIRT1, p-PI3K/PI3K y p-AKT/AKT en BMSC de ratones con osteoporosis. In vitro, el resveratrol aumentó la expresión de las proteínas SIRT1, p-PI3K/PI3K y p- AKT/AKT, Runx2, OSX y OCN, el nivel de deposición de calcio, la actividad de ALP y el contenido de osteocalcina en BMSC de manera dependiente de la concentración, mientras que La caída de SIRT1 revirtió significativamente el efecto del resveratrol. El resveratrol puede atenuar la osteoporosis al promover la diferenciación osteogénica de las células madre mesenquimales de la médula ósea, y el mecanismo puede estar relacionado con la regulación de la vía SIRT1/PI3K/AKT.

Effects of exercise training combined with acupuncture and moxibustion on fatigue / Efeitos do treinamento de exercício combinado à acupuntura e moxabustão sobre a fadiga / Efectos del entrenamiento físico combinado con acupuntura y moxibustión sobre la fatiga

ABSTRACT Introduction: Muscle fatigue bothers athletes, affecting training level and competitive performance, it also has a great impact on the physical health of athletes, predisposing them to accidents and an early termination of their career. Relieving sports fatigue is the focus of research in the field of sports health nowadays. Objective: Study the effect of acupuncture and moxibustion rehabilitation combined with physical training on sports fatigue. Methods: A controlled experiment was used. The experimental group used acupuncture and moxibustion combined with exercise training, while the control group used acupuncture and moxibustion. The same group of doctors performed the acupuncture and moxibustion treatment according to the actual situation of the patients, and they tested the changes in VAS pain score and PRI pain score. Results: The VAS pain score in the experimental group was 7.88 points before the procedure and 2.96 points after the sixth week of the procedure. The control group score was 7.67 before the start and 5.03 after training. The total PRI pain score in the experimental group was 6.52 points before training and 2.05 points in the sixth week of training. The control group scored 6.66 before the procedure and 3.89 in the sixth week. Conclusion: The combination of training and exercises can achieve a better rehabilitation effect compared to the isolated treatment of acupuncture and moxibustion. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: A fadiga muscular incomoda os atletas, afetando o nível de treinamento e o desempenho competitivo, também tem um grande impacto sobre a saúde física dos atletas, predispondo a acidentes e a um término precoce da carreira. Aliviar a fadiga esportiva é o foco da pesquisa no campo da saúde esportiva nos dias de hoje. Objetivo: Estudar o efeito de reabilitação pela acupuntura e moxabustão combinada com o treinamento físico sobre a fadiga esportiva. Métodos: Foi utilizado um experimento controlado. O grupo experimental usou acupuntura e moxabustão combinadas com treinamento com exercícios, enquanto o grupo de controle usou acupuntura e moxabustão. O mesmo grupo de médicos realizou o tratamento de acupuntura e moxabustão de acordo com a situação real dos pacientes, e testaram as alterações do escore de dor VAS e do escore de dor PRI. Resultados: A pontuação de dor VAS no grupo experimental foi de 7,88 pontos antes do procedimento e 2,96 pontos após a sexta semana de procedimento. A pontuação do grupo de controle foi 7,67 antes do início e 5,03 após o treinamento. A pontuação total de dor PRI no grupo experimental foi 6,52 pontos antes do treinamento e 2,05 pontos na sexta semana de treinamento. A pontuação do grupo de controle foi de 6,66 antes do procedimento e 3,89 na sexta semana. Conclusão: A combinação do treinamento com exercícios pode alcançar um melhor efeito de reabilitação em comparação com o tratamento isolado de acupuntura e moxabustão. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: La fatiga muscular molesta a los deportistas, ya que afecta al nivel de entrenamiento y al rendimiento competitivo, además de tener un gran impacto en la salud física de los atletas, predisponiendo a accidentes y al cese prematuro de la carrera. En la actualidad, el alivio de la fatiga deportiva es objeto de investigación en el campo de la salud deportiva. Objetivo: Estudiar el efecto de la rehabilitación mediante acupuntura y moxibustión combinada con entrenamiento físico sobre la fatiga deportiva. Métodos: Se utilizó un experimento controlado. El grupo experimental utilizó acupuntura y moxibustión combinadas con entrenamiento físico, mientras que el grupo de control utilizó acupuntura y moxibustión. El mismo grupo de médicos realizó el tratamiento de acupuntura y moxibustión de acuerdo con la situación real de los pacientes, y comprobó los cambios en la puntuación del dolor según VAS y la puntuación del dolor según PRI. Resultados: La puntuación VAS del dolor en el grupo experimental fue de 7,88 puntos antes del procedimiento y de 2,96 puntos después de la sexta semana del procedimiento. La puntuación del grupo de control fue de 7,67 antes del inicio y de 5,03 después del entrenamiento. La puntuación total del dolor PRI en el grupo experimental fue de 6,52 puntos antes del entrenamiento y de 2,05 puntos en la sexta semana de entrenamiento. La puntuación del grupo de control era de 6,66 antes del procedimiento y de 3,89 a la sexta semana. Conclusión: La combinación de entrenamiento con ejercicios puede lograr un mejor efecto rehabilitador en comparación con el tratamiento aislado de acupuntura y moxibustión. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Safety and prevention of sports injuries in popular ice and snow sports / Segurança e prevenção de lesões esportivas em esportes populares no gelo e neve / Seguridad y prevención de lesiones deportivas en los deportes populares de hielo y nieve

ABSTRACT Introduction: Following the development of ice and snow sports tourism projects, the hidden dangers of early extensive construction have gradually emerged. It mainly manifests itself in the sports safety of ice and snow sports tourism projects. Objective: Explore the management strategy of sports safety under the snow and ice sports tourism landscape. Methods: Literature research, interviews, and questionnaires were used to analyze the development in the study area of ice and snow tourism, the tourists themselves, and regional site construction. Finally, the paper analyzes strategies to improve sports safety management in related areas from the landscape manager's point of view. Results: The development of snow and ice sports tourism projects in the study area is satisfactory; however, due to the epidemic's impact, the current situation is relatively low, showing a trend of slow improvement. In terms of sports injury risk, after optimal training and safety management, the proportion of climatic characteristics of the site was 24.81%; the proportion of the population on the ski slopes was 40.92%; the proportion of equipment cleaning and maintenance was 59.23%; the degree of congestion on the ski slopes was 41.30%; the proportion of public safety was 34.42%; the proportion of basic emergency medical treatment was 32.30%; epidemics and other infectious diseases accounted for 83.13% of the total. Follow-up is done before the start, in the process, and after the occurrence of multiple managements. Conclusion: The safety management strategy of snow and ice sports tourism combines the factors of tourists and managers, and has great practical significance, so it is worthy of promotion. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: Com o desenvolvimento de projetos de turismo esportivo no gelo e na neve, os perigos ocultos da construção extensiva precoce têm surgido gradualmente. Ele se manifesta principalmente na segurança esportiva de projetos de turismo de esportes de gelo e neve. Objetivo: Explorar a estratégia de gestão da segurança esportiva sob o panorama do turismo esportivo de neve e gelo. Métodos: Pesquisa bibliográfica, entrevistas e questionários foram usados para analisar o desenvolvimento na área de estudo do turismo de gelo e neve, e dos próprios turistas bem como a construção de locais regionais. Finalmente, do ponto de vista do gerente de paisagens, o trabalho analisa as estratégias para melhorar a gestão da segurança esportiva em áreas relacionadas. Resultados: O desenvolvimento de projetos de turismo esportivo de neve e gelo na área de estudo é satisfatório, porém, devido ao impacto da epidemia, a situação atual é relativamente reduzida, mostrando uma tendência de lenta melhoria. Em termos de risco de lesões esportivas, após treinamento otimizado e gerenciamento da segurança, a proporção de características climáticas do local foi de 24,81%; a proporção de população nas pistas de esqui foi de 40,92%; a proporção de limpeza e manutenção dos equipamentos foi de 59,23%; o grau de congestionamento das pistas de esqui foi de 41,30%; a proporção de segurança pública foi de 34,42%; a proporção de tratamento médico básico de emergência foi de 32,30%; epidemias e outras doenças infecciosas representaram 83,13% do total. O acompanhamento é feito antes do início, no processo, e após a ocorrência de múltiplas gestões. Conclusão: A estratégia de gerenciamento de segurança do turismo esportivo de neve e gelo combina os fatores de turistas e gerentes, e tem grande significado prático, por isso é digna de promoção. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: Con el desarrollo de los proyectos turísticos de deportes de hielo y nieve, han ido apareciendo gradualmente los peligros ocultos de la construcción extensiva temprana. Se manifiesta principalmente en la seguridad deportiva de los proyectos turísticos de deportes de hielo y nieve. Objetivo: Explorar la estrategia de gestión de la seguridad deportiva en el marco del paisaje turístico de los deportes de nieve y hielo. Métodos: Se utilizó la investigación bibliográfica, entrevistas y cuestionarios para analizar el desarrollo en la zona de estudio del turismo de hielo y nieve, y a los propios turistas, así como la construcción de emplazamientos regionales. Por último, desde el punto de vista del gestor del paisaje, se analizan estrategias para mejorar la gestión de la seguridad deportiva en ámbitos afines. Resultados: El desarrollo de proyectos de turismo deportivo de nieve y hielo en la zona de estudio es satisfactorio, sin embargo, debido al impacto de la epidemia, la situación actual es relativamente baja, mostrando una tendencia de lenta mejora. En cuanto al riesgo de lesiones deportivas, tras optimizar la formación y la gestión de la seguridad, la proporción de características climáticas del lugar fue del 24,81%; la proporción de población en las pistas de esquí fue del 40,92%; la proporción de limpieza y mantenimiento del equipo fue del 59,23%; el grado de congestión de las pistas de esquí fue del 41,30%; la proporción de seguridad pública fue del 34,42%; la proporción de tratamiento médico básico de urgencia fue del 32,30%; las epidemias y otras enfermedades infecciosas representaron el 83,13% del total. El seguimiento se realiza antes del inicio, en el proceso y después de que se produzcan múltiples gestiones. Conclusión: La estrategia de gestión de la seguridad del turismo deportivo de nieve y hielo combina los factores de los turistas y los gestores, y tiene una gran importancia práctica, por lo que merece ser promovida. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Conocimientos y prácticas de los médicos cubanos respecto a Enterobacterales resistentes a carbapenémicos / Knowledge and practice on carbapenem-resistant Enterobacterales in medical doctors from a tertiary hospital in Cuba

Introducción: En el contexto de la pandemia de COVID-19, la infección por Enterobacterales resistentes a carbapenémicos productores de carbapenemasas (ERC-PC) se convierte en un problema de salud pública desafiante a nivel mundial. Los médicos desempeñan un papel fundamental en el manejo clínico de las infecciones por patógenos resistentes a carbapenémicos a nivel hospitalario y por ende en el control de estas. Sin embargo, no existen estudios sobre el conocimiento y prácticas de estos sobre ERC-PC en Cuba. Objetivo: Abordar conocimientos y prácticas sobre las infecciones por ERC-PC, su manejo terapéutico, prevención y control en médicos cubanos en un hospital terciario. Métodos: Se realizó un estudio observacional (descriptivo, de corte transversal) y se aplicó un cuestionario específico elaborado a 70 médicos asistenciales. Resultados: Hubo variabilidad en las opiniones sobre las ERC-PC y un conocimiento medio sobre estas en la mayoría de los encuestados. El 58,6 % de los médicos tenía experiencia en el manejo clínico de la infección por ERC-PC. Las brechas de conocimiento encontradas estuvieron asociadas a la escasa experiencia práctica en el manejo de casos. Hubo diferencia estadísticamente significativa en el nivel de conocimientos sobre los ERC-PC en los médicos con experiencia en el manejo de los ERC-PC en comparación con los médicos sin experiencia (p = 0,039). Conclusiones: Es necesario establecer un plan de formación continua en la temática para mejorar el desempeño de los profesionales de la salud en el control de las infecciones por ERC-PC y en el uso optimizado de los antibióticos.

Introduction: In the context of COVID-19 pandemic, carbapenemase-producing carbapenem-resistant Enterobacterales (CP-CRE) infection becomes a global public health threat. Medical doctors play a fundamental role in the clinical management and control of infections caused by carbapenem-resistant pathogens. However, in Cuba there are not previous studies on the knowledge and practice of medical doctors about CR-CRE. Objective: To study the knowledge and practice of Cuban medical doctors in a tertiary hospital about CR-CRE infections, their clinical management, prevention and control. Methods: It was conducted an observational study (descriptive, cross-sectional) and an specific questionnaire to 70 medical doctors was applied. Results: There was variability on the opinions about CP-CRE and average knowledge in the majority of the respondents. 58.6% of the medical doctors had some experience in the clinical management of CP-CRE infections. Knowledge gaps were associated with the limited practical experience in the management of cases. There was statistically significant difference in the level of knowledge about CP-CRE of medical doctors with experience in the management of CP-CRE compared to inexperienced medical doctors (p = 0.039). Conclusions: It is necessary to establish a continuous training plan on this topic to improve the performance of health professionals in the control of CP-CRE infections and in the appropriate use of antibiotics.

Serotipos y resistencia antimicrobiana de Streptococcus pneumoniae en población pediátrica china: una revisión de alcance

Esta revisión tuvo como propósito explorar la distribución de serotipos y la resistencia antimicrobiana de Streptococcus pneumoniae en la población pediátrica de China a partir de literatura publicada en los últimos seis años. Se realizó una revisión de alcance a partir de PubMed y dos bases de datos de China: CNKI y WanFang Data. Del total de 196 artículos extraídos, se seleccionaron 14 estudios para esta revisión. Hay 13 artículos que analizan la distribución de serotipos de Streptococcus pneumoniae; los serotipos más frecuentemente registrados son: 19F, 19A, 23F, 14 y 6B. Hay 11 artículos que analizan la resistencia antimicrobiana de Streptococcus pneumoniae, la prevalencia de no susceptibles a la penicilina se encuentra en el rango de 0 % a 95,7 %. Los aislados son muy resistentes a eritromicina, clindamicina, tetraciclina y trimetoprima-sulfametoxazol; son resistentes a penicilina en meningitis neumocócica pero son sensibles a penicilina en otras enfermedades neumocócicas, además, son muy sensibles a levofloxacina, vancomicina y Linezolid. Se concluye que la vacuna antineumocócica conjugada 13 tiene alta cobertura en los serotipos de Streptococcus pneumoniae en los niños de China continental, por eso se recomienda su inclusión en el programa de vacunación infantil; al mismo tiempo, se debe tener en cuenta la aparición de la sustitución de serotipos. Por eso, se deben incluir más pacientes pediátricos o niños en las investigaciones, especialmente los menores de cinco años. Es necesaria una vigilancia de alta calidad a largo plazo sobre la distribución de serotipos y resistencia antimicrobiana de Streptococcus pneumoniae para el desarrollo de la prevención de enfermedades neumocócicas.

This review aimed to explore the serotype distribution and antimicrobial resistance of Streptococcus pneumoniae in the Chinese pediatric population based on literature published in the last six years. A scoping review was performed using PubMed and two Chinese databases: CNKI and WanFang Data. Of the total of 196 articles extracted, 14 studies were selected for this review. There are 13 articles that analyze the distribution of Streptococcus pneumoniae serotypes, the most frequently registered serotypes are: 19F, 19A, 23F, 14 and 6B. There are 11 articles that analyze the antimicrobial resistance of Streptococcus pneumoniae, the prevalence of non-susceptible to penicillin is in the range of 0% to 95.7%. Isolates are highly resistant to erythromycin, clindamycin, tetracycline, and trimethoprim-sulfamethoxazole; they are resistant to penicillin in pneumococcal meningitis but are sensitive to penicillin in other pneumococcal diseases, in addition, they are very sensitive to levofloxacin, vancomycin and Linezolid. It is concluded that the pneumococcal conjugate vaccine 13 has high coverage in Streptococcus pneumoniae serotypes in children from mainland China, therefore its inclusion in the childhood vaccination program is recommended; at the same time, the occurrence of serotype substitution should be taken into account. Therefore, more pediatric patients or children should be included in research, especially those under five years of age. Long-term, high-quality surveillance of the serotype distribution and antimicrobial resistance of Streptococcus pneumoniae is necessary for the development of pneumococcal disease prevention.

A Retrospective Study of Risk Factors, Mortality, and Treatment Outcomes for Infections with Carbapenemase-Producing Enterobacterales in a Tertiary Hospital in Havana, Cuba.

(1) Background: The spread of carbapenem-resistant Enterobacterales in hospitals constitutes an important epidemiological and therapeutic problem that especially affects vulnerable patients such as perioperative patients. (2) Methods: We conducted a descriptive, observational, retrospective case-control study of patients infected with carbapenemase-producing carbapenem-resistant Enterobacterales (CP-CRE) and carbapenem-susceptible Enterobacterales during the perioperative period in a tertiary hospital. (3) Results: Metallo-ß-lactamase was detected in all 124 CRE isolates, with NDM-type carbapenemase being dominant, while 3 isolates coproduced KPC-type enzyme and showed high resistance rates against all antibiotics except colistin (25.2%). By analyzing the risk factors for infection, steroid use (OR: 3.22, p < 0.01), prior use of two or more antibiotics (OR: 4.04, p = 0.01), prior use of broad-spectrum cephalosporins (OR: 2.40, p = 0.04), and prior use of carbapenem (OR: 4.77, p = 0.03) were found to be independent risk factors for CP-CRE infection. In addition, in this study, we observed that the clinical outcomes of bloodstream infections and pneumonia associated with CP-CRE posed higher mortality risks. However, by analyzing the associations between treatment options and mortality, it was found that, in bloodstream infections caused by CP-CRE, colistin-based regimens showed a significant advantage (PR = 0.40, p = 0.03). (4) Conclusions: High mortality is associated with nosocomial infections in the perioperative period caused by carbapenemase-producing Enterobacterales, the dissemination of which in health care settings in Cuba remains a public health challenge.

Carbapenamase-Producing Acinetobacter baumannii in China, Latin America and the Caribbean.

INTRODUCTION: Carbapenem-resistant Acinetobacter baumannii is a complex health problem, causing difficulties in clinical-therapeutic management worldwide. It is of particular concern in Latin America, the Caribbean and China, where it is an emerging health problem. Carbapenemases produced by these organisms inactivate carbapenem antibiotics. Monitoring circulating genotypes' geographic dispersion contributes to more effective control measures. However, exhaustive studies on carbapenem-resistant A. baumannii are scarce. OBJECTIVES: Study the production of carbapenemases in clinical isolates of A. baumannii resistant to carbapenem antibiotics and the geographic distribution of the sequences circulating in China, Latin America and the Caribbean. DATA ACQUISITION: We followed PRISMA indications. We carried out a systematic search in Pubmed, BVS and CKNI on papers on A. baumannii and carbapenemases published during 2015-2020 in English, Spanish and Chinese, and selected 29 cross-sectional studies that met the search criteria. Studies were evaluated using JBI Critical Appraisal tools, and quantitative data were collated for meta-analysis using the Metaprop library in Stata15. DEVELOPMENT: OXA-type carbapenemases were detected in all studies; among A. baumannii resistant to carbapenem antibiotics, predominant types were OXA-23, OXA-24, OXA-54 and OXA-72; metallobetalactamases were identified less frequently than OXA carbapenemases. Only one clinical isolate producer of Class A carbapenemases (KPC) was identified in Colombia. In total, 41 sequence types were identified; in Latin America and the Caribbean the most common types were: ST79, ST25, ST1 and ST15; in China, the sequences ST195, ST208, ST191, ST368 and ST369 were the most prevalent. ST2 was found in both regions. CONCLUSIONS: The most prevalent carbapenemases and sequence types vary by region, indicating different ancestral strains. Microbiological surveillance, antibiotic use optimization, adequate infection treatment and timely control strategies are essential for carbapenem-resistant A. baumannii prevention and control in geographies such as Latin America, the Caribbean and China where such resistance is an emerging health problem.

Depalmitoylation rewires FLT3-ITD signaling and exacerbates leukemia progression.

Internal tandem duplication within FLT3 (FLT3-ITD) is one of the most frequent mutations in acute myeloid leukemia (AML) and correlates with a poor prognosis. Whereas the FLT3 receptor tyrosine kinase is activated at the plasma membrane to transduce PI3K/AKT and RAS/MAPK signaling, FLT3-ITD resides in the endoplasmic reticulum and triggers constitutive STAT5 phosphorylation. Mechanisms underlying this aberrant FLT3-ITD subcellular localization or its impact on leukemogenesis remain poorly established. In this study, we discovered that FLT3-ITD is S-palmitoylated by the palmitoyl acyltransferase ZDHHC6. Disruption of palmitoylation redirected FLT3-ITD to the plasma membrane and rewired its downstream signaling by activating AKT and extracellular signal-regulated kinase pathways in addition to STAT5. Consequently, abrogation of palmitoylation increased FLT3-ITD-mediated progression of leukemia in xenotransplant-recipient mouse models. We further demonstrate that FLT3 proteins were palmitoylated in primary human AML cells. ZDHHC6-mediated palmitoylation restrained FLT3-ITD surface expression, signaling, and colonogenic growth of primary FLT3-ITD+ AML. More important, pharmacological inhibition of FLT3-ITD depalmitoylation synergized with the US Food and Drug Administration-approved FLT3 kinase inhibitor gilteritinib in abrogating the growth of primary FLT3-ITD+ AML cells. These findings provide novel insights into lipid-dependent compartmentalization of FLT3-ITD signaling in AML and suggest targeting depalmitoylation as a new therapeutic strategy to treat FLT3-ITD+ leukemias.

La humanidad enfrenta un desastre: la resistencia antimicrobiana / Humanity faces disaster: antimicrobial resistance

Introducción: La resistencia bacteriana pone en peligro la salud y la supervivencia de los seres humanos, aumenta la carga económica de la sociedad y los pacientes. Es un fenómeno global por lo que Cuba no queda exenta. Objetivos: Exponer el impacto social y económico de la resistencia antimicrobiana desde el punto de vista filosófico y describir el rol de una medida preventiva en la contención de la resistencia antimicrobiana. Material y Métodos: Se realizó una revisión de fuentes bibliográficas que fueron localizadas mediante la base de datos Pubmed, Portal Regional de la Biblioteca Virtual de Salud y el motor de búsqueda Google Académico. Desarrollo: Se analizan los aspectos sociales, económicos y éticos relacionados con la resistencia bacteriana y se ejemplifica una medida preventiva en la contención de la resistencia antimicrobiana. Además, se analiza la relación entre fármacos antibacterianos, resistencia bacteriana y medidas de prevención y control desde el punto de vista de ciencia-tecnología-sociedad. Conclusiones: La sociedad humana se desarrolla y progresa constantemente bajo la promoción de la ciencia y la tecnología. En pocas décadas, los antibióticos han pasado de ser "drogas milagrosas de gran impacto para la salud" a ser "un recurso no renovable en vías de extinción". Se deben adoptar las acciones pertinentes para frenar el desarrollo de la resistencia bacteriana con un enfoque multisectorial. Se requiere una gobernanza, optimización del uso de antibióticos, apoyos de políticas de salud y un fortalecimiento de los programas de prevención y control de infecciones(AU)

Introduction: Bacterial resistance endangers the health and survival of human beings and increases the economic burden on society and patients. It is a global phenomenon; therefore, Cuba is not exempted from it. Objective: To present the social and economic impact of antimicrobial resistance from a philosophical point of view as well as to describe the role of a preventive measure to stop antimicrobial resistance. Material and Methods: A review of bibliographic sources was carried out in databases such as PubMed and the Regional Portal of the Virtual Health Library; Google Scholar search engine was also used. Development: Social, economic and ethical aspects related to bacterial resistance are analyzed. A preventive measure to stop antimicrobial resistance is described. In addition, the relationship between antibacterial drugs, bacterial resistance and prevention and control measures is analyzed from the point of view of science-technology-society. Conclusions: Human society is constantly developing and progressing under the promotion of science and technology. In just a few decades, antibiotics have gone from being "miracle drugs of great impact on health" to being "a non-renewable resource in danger of extinction". Necessary measures such as the optimization of the use of antibiotics, a health policy support, and a health strategy for the prevention and control of infections must be taken to stop the development of bacterial resistance(AU)

Clinical evaluation of modified ALPPS procedures based on risk-reduced strategy for staged hepatectomy.

INTRODUCTION AND OBJECTIVES: Radical resection remains the only curative treatment for liver tumors. Although associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) can increase the resection rate, huge controversy exists for high reported mortality and morbidity. This study was to evaluate the efficacy and safety of modified ALPPS procedure. PATIENTS AND METHODS: Patients who were performed ALPPS in single-center in recent 5 years were retrospectively reviewed. The modified strategy included strict patient selection, precise future liver remnant (FLR) assessment and operation planning, and usage of minimally invasive methods. Data including clinical records, functional FLR increase, complications, and overall survival (OS) were analyzed. RESULTS: Sixty patients underwent modified ALPPS procedure and recovered well. No severe complications happened after the 1-stage operation, and the increasing FLR was 179.3 cm3(±72.4 cm3), with similar functional FLR increase. The OS was 20.0 months (±4.5month). CONCLUSIONS: ALPPS could be a feasible treatment for complex liver tumors by risk-reduced modification. It could be expected to provide long-term survival for patients without enough FLR.

Serotypic distribution and antimicrobial resistance of Streptococcus pneumoniae in Chinese children under 5 years after the introduction of the 13-valent conjugate pneumococcal vaccine: protocol for a scoping review.

The World Health Organization (WHO) recommends that pneumococcal conjugate vaccines (PCVs) be included in immunization programs worldwide. In China, the 7-valent pneumococcal conjugate vaccine (PREVNAR 7®) was authorized in 2008 but was not included in the national immunization programs. In 2016, PREVNAR 13®, a 13-valent pneumococcal conjugate vaccine (PCV13), was licensed for optional use in China. We will conduct a scoping review of the distribution of serotypes and antimicrobial resistance of Streptococcus pneumoniae in children aged under 5 years in China since the introduction of PCV13. We will obtain data from PubMed, the China National Knowledge Infrastructure (CNKI), and Wanfang Med Online. We will also review epidemiological data from WHO and the China Antimicrobial Surveillance Network (CHINET). Our analysis will include the condition of interest, the intervention, and the geographical region. All types of studies will be eligible for inclusion in the study database if they meet the inclusion criteria. This scoping review is intended to outline how S. pneumoniae serotypes are distributed, and it will map their antimicrobial resistance in children aged under 5 years in China. The results of this study will provide useful information on the impact of PCV13 in China.

Serum alanine transaminase levels predict type 2 diabetes risk among a middle-aged and elderly Chinese population.

INTRODUCTION AND AIM: It is indicated that high levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are associated with increased incident type 2 diabetes risk. However, whether serum ALT levels could improve the discrimination of type 2 diabetes remains unclear. METHODS: The data was derived from the Dongfeng-Tongji cohort study, which was established in 2008 and followed until October 2013. A total of 17,173 participants free of type 2 diabetes at baseline were included and 1159 participants developed diabetes after 4.51 (0.61) years of follow-up. Cox proportional hazard regression model was used to calculate the hazard ratios (HRs) for the association between ALT and AST levels with incident diabetes risk. Receiver-operating characteristic (ROC) curves analysis was used to evaluate the predictive accuracy of models incorporating traditional risk factors with and without ALT. RESULTS: Compared with the lowest quartile of ALT and AST levels, the highest quartile had a significantly higher risk of developing type 2 diabetes (HR: 2.17 [95% CI: 1.78-2.65] and 1.29 [1.08-1.54], respectively) after adjustment for potential confounders. The addition of ALT levels into the traditional risk factors did not improve the predictive ability of type 2 diabetes, with AUC increase from 0.772 to 0.774; P=0.86. CONCLUSIONS: Although elevated ALT or AST levels increased incident type 2diabetes risk, addition of ALT levels into the prediction model did not improve the discrimination of type 2 diabetes.

Long non-coding RNA AFAP1-AS1 facilitates tumor growth and promotes metastasis in colorectal cancer.

BACKGROUND AND OBJECTIVE: Long non-coding RNAs can regulate tumorigenesis of various cancers. Dys-regulation of lncRNA-AFAP1-AS1 has not been studied in colorectal carcinoma (CRC). This study was to examine the function involvement of AFAP1-AS1 in tumor growth and metastasis of CRC. METHODS: Relative expression of AFAP1-AS1 in CRC tissues and CRC cells lines was determined using quantitative real-time PCR (qRT-PCR). Functional involvement of AFAP1-AS1 in tumor proliferation and metastasis was evaluated in AFAP1-AS1-specific siRNA-treated CRC cells and in CRC cell xenograft. Expression of epithelial-mesenchymal transition (EMT)-related gene expression was determined using western blot. RESULTS: Relative expression of AFAP1-AS1 was significantly elevated in CRC tissues and CRC HCT116 and SW480 cell lines. AFAP1-AS1 knock-down suppressed SW480 cell proliferation, colony formation, migration and invasion. Also AFAP1-AS1 knock-down inhibited tumor metastasis-associated genes expression in terms of EMT. This carcinostatic action by AFAP1-AS1 knock-down was further confirmed by suppression of tumor formation and hepatic metastasis of CRC cells in nude mice. CONCLUSION: lncRNA-AFAP1-AS1 knock-down exhibits antitumor effect on colorectal carcinoma in respects of suppression of cell proliferation and metastasis of cancer cells.

Long non-coding RNA AFAP1-AS1 facilitates tumor growth and promotes metastasis in colorectal cancer

BACKGROUND AND OBJECTIVE: Long non-coding RNAs can regulate tumorigenesis of various cancers. Dys-regulation of lncRNA-AFAP1-AS1 has not been studied in colorectal carcinoma (CRC). This study was to examine the function involvement of AFAP1-AS1 in tumor growth and metastasis of CRC. METHODS: Relative expression of AFAP1-AS1 in CRC tissues and CRC cells lines was determined using quantitative real-time PCR (qRT-PCR). Functional involvement of AFAP1-AS1 in tumor proliferation and metastasis was evaluated in AFAP1-AS1-specific siRNA-treated CRC cells and in CRC cell xenograft. Expression of epithelial-mesenchymal transition (EMT)-related gene expression was determined using western blot. RESULTS: Relative expression of AFAP1-AS1 was significantly elevated in CRC tissues and CRC HCT116 and SW480 cell lines. AFAP1-AS1 knock-down suppressed SW480 cell proliferation, colony formation, migration and invasion. Also AFAP1-AS1 knock-down inhibited tumor metastasis-associated genes expression in terms of EMT. This carcinostatic action by AFAP1-AS1 knock-down was further confirmed by suppression of tumor formation and hepatic metastasis of CRC cells in nude mice. CONCLUSION: lncRNA-AFAP1-AS1 knock-down exhibits antitumor effect on colorectal carcinoma in respects of suppression of cell proliferation and metastasis of cancer cells.

Mechanisms involved in the cytotoxic effects of berberine on human colon cancer HCT-8 cells

Berberine, a constituent of some traditional Chinese medicinal plants, has been reported to have cytotoxicity effects on different human cancer cell lines. There is no available information about the effects and mechanism of action of berberine on human colon cancer cell line HCT-8. In this paper, the cytotoxicity of berberine on HCT-8 cancer cells was investigated by MTT assay, fluorescence microscopy and flow cytometry analysis. Our data revealed that berberine could significantly inhibit the growth of HCT-8 cells in a dose- and time-dependent manner. Morphology of apoptotic cells was studied with acridine orange/ethidium bromide staining. The concentrations of lactate dehydrogenase and both acid and alkaline phosphatases were significantly increased in cell supernatants after berberine treatment, suggesting cell death. Furthermore, flow cytometry analysis showed that berberine could arrest HCT-8 cells at S phase in a time-dependent manner. To further investigate the apoptotic molecular mechanism, reverse transcription-polymerase chain reaction (RT-PCR) and western blotting methods were used. The up-regulated mRNA and/or protein expressions of Fas, FasL, TNF-a, caspase-3 and down-regulation of pro-caspase-3 suggest that the death receptor pathway may be involved in the apoptotic pathway induced by berberine. Decrease of Bcl-2 and increase of Bax in mRNA and/or protein expressions showed that the Bcl-2 family proteins were involved in berberine-induced apoptosis. We also found that berberine-induced apoptosis was associated with an up-regulated expressions of p53 and prohibitin (PHB), and decreased vimentin expression. These results suggest that berberine can suppress cell growth and reduce cell survival by arresting the cell-cycle and by inducing apoptosis of HCT-8 cells.

Mechanisms involved in the cytotoxic effects of berberine on human colon cancer HCT-8 cells

Berberine, a constituent of some traditional Chinese medicinal plants, has been reported to have cytotoxicity effects on different human cancer cell lines. There is no available information about the effects and mechanism of action of berberine on human colon cancer cell line HCT-8. In this paper, the cytotoxicity of berberine on HCT-8 cancer cells was investigated by MTT assay, fluorescence microscopy and flow cytometry analysis. Our data revealed that berberine could significantly inhibit the growth of HCT-8 cells in a dose- and time-dependent manner. Morphology of apoptotic cells was studied with acridine orange/ethidium bromide staining. The concentrations of lactate dehydrogenase and both acid and alkaline phosphatases were significantly increased in cell supernatants after berberine treatment, suggesting cell death. Furthermore, flow cytometry analysis showed that berberine could arrest HCT-8 cells at S phase in a time-dependent manner. To further investigate the apoptotic molecular mechanism, reverse transcription-polymerase chain reaction (RT-PCR) and western blotting methods were used. The up-regulated mRNA and/or protein expressions of Fas, FasL, TNF-a, caspase-3 and down-regulation of pro-caspase-3 suggest that the death receptor pathway may be involved in the apoptotic pathway induced by berberine. Decrease of Bcl-2 and increase of Bax in mRNA and/or protein expressions showed that the Bcl-2 family proteins were involved in berberine-induced apoptosis. We also found that berberine-induced apoptosis was associated with an up-regulated expressions of p53 and prohibitin (PHB), and decreased vimentin expression. These results suggest that berberine can suppress cell growth and reduce cell survival by arresting the cell-cycle and by inducing apoptosis of HCT-8 cells.(AU)