Ergosterol peroxide (EP) has been extensively studied for its antitumor activities. However, its further development has been restricted due to its limited intracellular accumulation and poor aqueous solubility. In this study, a novel triphenylphosphonium cation (TPP+) moiety was coupled to ergosterol peroxide to precisely target it at tumor cell mitochondria. The synthesized Mito-EP derivatives Mito-EP-3a-3d displayed stronger cytotoxicity than the EP parent and exhibited selectively cytotoxic effects between cancer cells and normal gastric epithelial (GES-1) cells. The most potent compound, Mito-EP-3b, was 9.7-fold more efficacious than ergosterol peroxide in the MCF-7 (breast cancer) cell line and showed good selectivity (SI = IC50GES-1/IC50MCF-7 = 4.04, IC50: concentrations to inhibit 50% of cell growth). Furthermore, Mito-EP-3b was able to decrease the mitochondrial membrane potential and induced reactive oxygen species production, accompanied by activating the expression of cytochrome c and Bax, while Bcl-2 expression was suppressed. The molecular mechanism may refer to the mitochondrial apoptotic pathway. Overall, the above results incentivize the further study of Mito EP-3b derivatives as potent anticancer agents.

Introduction: Seed-based analysis has shown that transcutaneous auricular vagus nerve stimulation (taVNS) can modulate the dysfunctional brain network in patients with major depressive disorder (MDD). However, the voxel-based neuropsychological mechanism of taVNS on patients with first-episode MDD is poorly understood. The objective of this study was to assess the effects of an 8-week course of taVNS on patients with first-episode MDD. Methods: Twenty-two patients with first-episode MDD accepted an 8-week course of taVNS treatment. Resting-state functional magnetic resonance imaging (rs-fMRI) scans were performed before and after treatment. Voxel-based analyses were performed to characterize spontaneous brain activity. Healthy controls (n=23) were recruited to minimize test-retest effects. Analysis of covariance (ANCOVA) was performed to ascertain treatment-related changes. Then, correlations between changes in brain activity and the Hamilton Depression Rating Scale (HAM-D)/Hamilton Anxiety Scale (HAM-A) remission rate were estimated. Results: Significant group-by-time interactions on voxel-based analyses were observed in the inferior ventral striatum (VSi) and precuneus. Post-hoc analyses showed that taVNS inhibited higher brain activity in the VSi, while upregulating it in the precuneus. Functional connectivity (FC) between the VSi and precuneus decreased. Positive correlations were found between the HAM-D remission rate and changes in brain activity in the VSi. Conclusion: taVNS reduced the FC between VSi and precuneus by normalizing the abnormal spontaneous brain activity of VSi in first-episode MDD patients.

RESUMO Introdução Embora o futebol chines tenha experimentado muitas atualizações em seus métodos, ainda há uma grande discrepância em termos de resistência física dos jogadores quando comparados às potências mundiais. Portanto, fortalecer a resistência física dos jogadores de futebol através de métodos específicos de treinamento é um importante fator para a otimização do desempenho atual. Objetivo Estudar a aplicação do treinamento funcional no condicionamento físico dos jogadores de futebol. Métodos 20 atletas estudantes de educação física de futebol júnior em faculdades e universidades foram selecionados como objeto de pesquisa. A formação funcional global foi dividida em três etapas: estágio de prática, fase de adaptação e etapa de promoção. Os dados foram comparados, integrados e analisados antes e após a intervenção. Resultados A realização de treinamentos funcionais direcionados para jogadores de futebol pode efetivamente aumentar a resistência física dos atletas, reduzindo a ocorrência de lesões esportivas e melhorando a pontuação geral do condicionamento físico a nível técnico e de estabilidade. Conclusão A partir da pesquisa deste artigo, pode-se ver que há falta de aptidão física e força técnica no futebol chinês atual. A realização de treinamento funcional direcionado é relevante e merece ser aplicado ao treinamento de futebol. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

ABSTRACT Introduction Although Chinese soccer has experienced many updates in its methods, there is still a large gap in players’ physical endurance compared to the world powers. Therefore, strengthening soccer players’ physical endurance through specific training methods is important in optimizing current performance. Objective Study the application of functional training in soccer players’ physical conditioning. Methods 20 junior soccer physical education student-athletes in colleges and universities were selected as the research object. The global functional training was divided into three stages: practice, adaptation, and promotion. Data were compared, integrated, and analyzed before and after the intervention. Results Conducting targeted functional training for soccer players can effectively increase athletes’ physical endurance, reducing sports injuries and improving overall fitness scores at the technical and stability level. Conclusion From the research of this article, it can be seen that there is a lack of physical fitness and technical strength in Chinese soccer today. The performance of targeted functional training is relevant and should be applied to soccer training. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMEN Introducción Aunque el fútbol chino ha experimentado muchas actualizaciones en sus métodos, sigue habiendo una gran discrepancia en cuanto a la resistencia física de los jugadores si se compara con las potencias mundiales. Por lo tanto, reforzar la resistencia física de los futbolistas mediante métodos de entrenamiento específicos es un factor importante para optimizar el rendimiento actual. Objetivo Estudiar la aplicación del entrenamiento funcional en el acondicionamiento físico de los futbolistas. Métodos Se seleccionaron como objeto de investigación 20 estudiantes atletas de educación física de fútbol juvenil en colegios y universidades. El entrenamiento funcional global se dividió en tres etapas: etapa de práctica, etapa de adaptación y etapa de promoción. Los datos se compararon, integraron y analizaron antes y después de la intervención. Resultados La realización de un entrenamiento funcional específico para los futbolistas puede aumentar eficazmente la resistencia física de los deportistas, reduciendo la aparición de lesiones deportivas y mejorando la puntuación global de la aptitud a nivel técnico y de estabilidad. Conclusión De la investigación de este artículo se desprende que en el fútbol chino actual hay una falta de aptitud física y de fuerza técnica. El rendimiento del entrenamiento funcional dirigido es relevante y merece ser aplicado al entrenamiento del fútbol. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

RESUMO Introdução O aprimoramento das habilidades esportivas do futebol depende de muitos esforços de treinamento e está intimamente relacionado com métodos científicos intrínsecos. Atenção na qualidade integral dos músculos dos membros inferiores e a realização de exercícios específicos de movimentos técnicos é essencial para atingir o estado ótimo da performance física nos jogadores. Objetivo Analisar o efeito cinemático das técnicas de movimento dos membros inferiores no treinamento de futebol. Métodos 10 atletas foram marcados com esferas reflexivas e submetidos ao método de treinamento cinemático dos membros inferiores desenhado pelos treinadores num período de 60 minutos, três vezes por semana, durante 6 semanas. Antes e depois do experimento, os dados capturados por esferas reflexivas foram capturados, comparados, classificados e analisados. Resultados O treinamento cinemático pode otimizar efetivamente o tempo de movimento, amplitude de balanço, ângulo de balanço e outros aspectos da estrutura mecânica dos membros inferiores, melhorando assim o dispêndio energético e tornando o movimento conciso, transmitindo força e precisão. Conclusão Os treinadores devem estudar seriamente os princípios da análise cinemática aplicada, otimizar o programa de treinamento do ponto de vista científico, pois o nível esportivo dos atletas é melhorado significativamente com a adição desse feedback em tempo real. Nível de evidência II; Estudos terapêuticos - investigação dos desfechos do tratamento.

ABSTRACT Introduction The improvement of soccer sports skills depends on many training efforts and is closely related to intrinsic scientific methods. Attention to the integral quality of the lower limb muscles and the performance of specific exercises of technical movements is essential to reach the optimal state of physical performance in players. Objective Analyze the kinematic effect of lower limb movement techniques in soccer training. Methods 10 athletes were marked with reflective spheres and submitted to the kinematic training method of the lower limbs designed by the coaches in 60 minutes, three times a week, for six weeks. Before and after the experiment, data captured by reflective spheres were captured, compared, classified, and analyzed. Results Kinematic training can effectively optimize movement time, swing amplitude, swing angle, and other aspects of lower limb mechanical structure, thus improving energy expenditure and making the movement concise, conveying strength and precision. Conclusion Trainers should seriously study the principles of applied kinematic analysis and optimize the training program from a scientific point of view because the athletic level of athletes is significantly improved with this real-time feedback. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMEN Introducción La mejora de las capacidades deportivas en el fútbol depende de muchos esfuerzos de entrenamiento y está estrechamente relacionada con métodos científicos intrínsecos. La atención sobre la calidad integral de los músculos de los miembros inferiores y la realización de ejercicios específicos de movimientos técnicos es esencial para alcanzar el estado óptimo del rendimiento físico en los jugadores. Objetivo Analizar el efecto cinemático de las técnicas de movimiento del miembro inferior en el entrenamiento de fútbol. Métodos 10 atletas fueron marcados con esferas reflectantes y sometidos al método de entrenamiento cinemático de los miembros inferiores diseñado por los entrenadores en un período de 60 minutos, tres veces por semana, durante 6 semanas. Antes y después del experimento, se capturaron, compararon, clasificaron y analizaron los datos captados por las esferas reflectantes. Resultados El entrenamiento cinemático puede optimizar eficazmente el tiempo de movimiento, la amplitud del balanceo, el ángulo de balanceo y otros aspectos de la estructura mecánica de las extremidades inferiores, mejorando así el gasto de energía y haciendo que el movimiento sea conciso, transmitiendo fuerza y precisión. Conclusión Los entrenadores deberían estudiar seriamente los principios del análisis cinemático aplicado, optimizar el programa de entrenamiento desde un punto de vista científico, ya que el nivel atlético de los deportistas mejora significativamente con la incorporación de esta información en tiempo real. Nivel de evidencia II; Estudios terapêuticos - investigación de los resultados del tratamiento.

Abstract A Qingzhi compound-flavor Baijiu (QZCF Baijiu) was developed and the physiochemical factors and microbial community structure in Jiupei (fermented grains) during Baijiu fermentation were revealed. Physiochemical factors of ethanol, moisture and acidity significantly increased in the fermentation, while starch and reducing sugar decreased. The results of high-throughput sequencing showed that Weissella, Pediococcus, Bacillus, Pantoea, Streptococcus, Sphingobacterium, Saccharomyces, Rhizopus, Issatchenkia and Wickerhamomyces were the dominant microorganisms in Jiupei. Moreover, correlation analysis between the physicochemical factors, the dominant microorganisms and the important flavor compounds in QZCF Baijiu production highlighted that the changes of physiochemical factors would lead to the corresponding changes of core microbiota and important flavor substances. Physiochemical factors of starch, reducing sugar and temperature could significantly affect the microbial community structure at the early stage of fermentation, while the influences of ethanol content and acidity became greater at the later stage, resulting in the differences of flavor compounds in Jiupei. Therefore, the growth and metabolism of microbial communities could be regulated by purposefully adjusting the physiochemical factors, thereby improving the flavor and quality of Baijiu. This work enriched the flavor types of Baijiu and provided a reference for the Baijiu-making industries to manage their production process.

Abstract Umbilical cord mesenchymal stem cells (UMSCs) from fetal tissues have become a valuable source of cell regeneration therapy due to their low immunogenicity, high plasticity and antimicrobial peptides. Most researches about UMSCs mainly focused on humans, mice, rabbits and other mammals, but it is still unknown in broiler. To the best of our knowledge, we first established a broiler-derived UMSCs line from noncontroversial Wharton's jelly of umbilical cord. The detection of biological characteristics showed UMSCs showed the morphological characteristics of fibroblasts and could be cultured to 26 generations in vitro, and maintained diploid chromosomes (2n=78) by G-banding analysis. Cell cycle of UMSCs showed the rate of G0/G1 was about 76.7-80.9%. Moreover, UMSCs could express mesenchymal markers (CD29, CD90, CD71, and CD44), but not hematopoietic marker (CD34) and endothelial marker (CD31). Additionally, UMSCs could be efficiently induced to transdifferentiate into three germ layer cells, such as adipocytes, osteoblasts, chondrocytes, hepatocytes, epithelia, and neurogenic cells. These results demonstrated UMSCs have the essential characteristics of MSCs, and can be used as an attractive candidate for cell regenerative therapy and the study of regulatory mechanisms associated with selective differentiation.

ABSTRACT Introduction: Lower body perfusion (LBP) is a technique used to provide blood perfusion to distal organs and spinal cord during circulatory arrest. However, the effect of LBP on the prognosis of aortic arch surgery, especially on postoperative renal function, remains unclear. Methods: A total of 304 patients with acute type A aortic dissection who underwent total aortic arch replacement combined with frozen elephant trunk implantation between May 2016 and December 2021 were retrospectively analyzed. The patients were divided into LBP group (group L, n=85) and non-LBP group (group NL, n=219). Routine lower body circulatory arrest was applied during operation in group NL, and antegrade LBP combined was applied during operation in group L. Perioperative data were recorded. Propensity score matching was used for statistical analysis. Results: After propensity score matching, 85 pairs of patients were successfully matched. Two groups significantly differed in circulatory arrest time (six minutes vs. 30 minutes, P=0.000), cross-clamping time (101 minutes vs. 92 minutes, P=0.010), minimum nasopharyngeal temperature (29.4ºC vs. 27.2ºC, P=0.000), and highest lactate value during cardiopulmonary bypass (2.3 μmol/L vs. 4.1 μmol/L, P=0.000). Considering the postoperative indicators, the drainage volume (450 mL vs. 775 mL, P=0.000) and the incidence of level I acute kidney injury (23.5% vs. 32%, P=0.046) in group L was lower than those in group NL. Conclusion: LBP resulted as a safe and feasible approach in aortic arch surgery, as it could significantly shorten the circulatory arrest time, which might reduce the incidence of postoperative level I acute kidney injury.

ABSTRACT Introduction Sports injuries in soccer are hardly avoided due to the characteristics of battles, such as intense conflict and high-level competitiveness related to soccer. Objective Investigate the most common sports injuries in professional soccer players. Methods A questionnaire survey was carried out with 365 valid returns, including 198 male and 177 female professional soccer players. Data were collected and distributed using Excel software. Results Among sports injuries in professional soccer athletes, minor injuries are more frequent, and the lower limbs are the most affected. The subjective cause of these injuries is mainly overwork. Among the objective causes, many injuries caused by the sports characteristics of soccer are inevitable, having a strong connection with the intrinsic factors of the sport. Treating injuries combines traditional Chinese medicine with the advantages of Western medicine. Conclusion It is recommended that athletes focus constantly on their injuries while playing the sport. Coaches should verify the safety of the athletes, taking precautions to reduce injuries as much as possible and improve the athlete’s competitive level, prolonging his professional activity. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMEN Introducción Las lesiones deportivas en el fútbol son difícilmente evitables debido a las características de las batallas como el intenso conflicto y la alta competitividad relacionada con el fútbol. Objetivo Investigar las lesiones deportivas más comunes en los futbolistas profesionales. Métodos Se llevó a cabo una encuesta con 365 respuestas válidas, incluyendo 198 jugadores y 177 jugadoras de fútbol profesional. Los datos se recogieron y distribuyeron mediante el programa informático Excel. Resultados Entre las lesiones deportivas en los atletas de fútbol profesional, las lesiones menores son más frecuentes, y los miembros inferiores son los más afectados. La causa subjetiva de estas lesiones es principalmente el exceso de trabajo. Entre las causas objetivas, son inevitables muchas lesiones provocadas por las características deportivas del fútbol, que tienen una fuerte relación con los factores intrínsecos del deporte. Actualmente, el tratamiento de las lesiones tiende a combinar la medicina tradicional china con las ventajas de la medicina occidental. Conclusión Se recomienda a los atletas una concentración constante durante la práctica del deporte. Los entrenadores deben verificar la seguridad de los deportistas, tomando precauciones para reducir al máximo las lesiones, y mejorar el nivel competitivo del deportista, prolongando su actividad profesional. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

RESUMO Introdução As lesões esportivas do futebol dificilmente são evitadas devido as características de batalhas como o intenso conflito e a competitividade de alto nível relacionadas ao futebol. Objetivo Investigar as lesões esportivas mais acometidas nos jogadores profissionais de futebol. Métodos Efetuou-se uma pesquisa por questionário com 365 retornos válidos, incluindo 198 homens e 177 mulheres profissionais do esporte. Os dados foram coletados e distribuídos através do software Excel. Resultados Entre as lesões esportivas de atletas profissionais de futebol, as lesões de menor grau são mais frequentes, sendo os membros inferiores os mais afetados. A causa subjetiva dessas lesões é principalmente o excesso de trabalho. Entre as causas objetivas, muitas lesões causadas pelas características esportivas do futebol são inevitáveis, possuindo uma forte conexão com os fatores intrínsecos do esporte. Atualmente, o tratamento das lesões tende a combinar a medicina tradicional chinesa com as vantagens da medicina ocidental. Conclusão Recomenda-se aos atletas um foco constante durante a prática o esporte. Os treinadores devem verificar a segurança dos atletas, tomando precauções para reduzir ao máximo as lesões e melhorar o nível competitivo do atleta, prolongando sua atividade profissional. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

ABSTRACT Introduction: Lower body perfusion (LBP) is a technique used to provide blood perfusion to distal organs and spinal cord during circulatory arrest. However, the effect of LBP on the prognosis of aortic arch surgery, especially on postoperative renal function, remains unclear. Methods: A total of 304 patients with acute type A aortic dissection who underwent total aortic arch replacement combined with frozen elephant trunk implantation between May 2016 and December 2021 were retrospectively analyzed. The patients were divided into LBP group (group L, n=85) and non-LBP group (group NL, n=219). Routine lower body circulatory arrest was applied during operation in group NL, and antegrade LBP combined was applied during operation in group L. Perioperative data were recorded. Propensity score matching was used for statistical analysis. Results: After propensity score matching, 85 pairs of patients were successfully matched. Two groups significantly differed in circulatory arrest time (six minutes vs. 30 minutes, P=0.000), cross-clamping time (101 minutes vs. 92 minutes, P=0.010), minimum nasopharyngeal temperature (29.4ºC vs. 27.2ºC, P=0.000), and highest lactate value during cardiopulmonary bypass (2.3 μmol/L vs. 4.1 μmol/L, P=0.000). Considering the postoperative indicators, the drainage volume (450 mL vs. 775 mL, P=0.000) and the incidence of level I acute kidney injury (23.5% vs. 32%, P=0.046) in group L was lower than those in group NL. Conclusion: LBP resulted as a safe and feasible approach in aortic arch surgery, as it could significantly shorten the circulatory arrest time, which might reduce the incidence of postoperative level I acute kidney injury.

ABSTRACT Due to its high nutritional value, broccoli (Brassica oleracea var. italica Plenck) is one of the most popular vegetables worldwide. This study assessed 36 phenotypic characteristics of 111 broccoli varieties to understand the phenotypic diversity of new broccoli varieties and improve their breeding speed with advantages and characteristics in China, including 108 new varieties and three varieties of common knowledge. The genetic diversity, the principal component, and the cluster of phenotypic characteristics of broccoli varieties were further investigated. The results showed that the coefficients of variation of 36 characteristics ranged between 11.18 % and 94.99 %, with their diversity index between 0.26 and 1.82. The 111 broccoli varieties were further classified into eight groups, primarily attributed to the differences in phenotypic characteristics, including curd weight, main stem thickness, plant development degree, plant height, and anthocyanin coloration. The cumulative contribution rate of the first five principal components reached 81.186 %, corresponding to 12 representative phenotypic traits. The analysis indicated that the phenotypic characteristics of broccoli were rich in diversity, especially for several characteristics appreciated by the market, such as weight, curd firmness, and anthocyanin coloration. This study revealed the basic information on the genetic diversity of new broccoli varieties in China from 2017 to 2019 and provided potential breeding strategies for broccoli to meet diverse market demands.

ABSTRACT The advancement of neuroimaging technology offers a pivotal reference for the early detection of mild cognitive impairment (MCI), a significant area of focus in contemporary cognitive function research. Structural MRI scans present visual and quantitative manifestations of alterations in brain tissue, whereas functional MRI scans depict the metabolic and functional state of brain tissues from diverse perspectives. As various magnetic resonance techniques possess both strengths and constraints, this review examines the methodologies and outcomes of multimodal magnetic resonance technology in MCI diagnosis, laying the groundwork for subsequent diagnostic and therapeutic interventions for MCI.

RESUMO O avanço da tecnologia de neuroimagem oferece uma referência fundamental para a detecção precoce do comprometimento cognitivo leve (CCL), uma área significativa de foco na pesquisa contemporânea da função cognitiva. A ressonância magnética estrutural apresenta manifestações visuais e quantitativas de alterações no tecido cerebral, enquanto a ressonância magnética funcional retrata o estado metabólico e funcional dos tecidos cerebrais sob diversas perspectivas. Como várias técnicas de ressonância magnética possuem pontos fortes e restrições, esta revisão examinou as metodologias e os resultados da tecnologia de ressonância magnética multimodal no diagnóstico de CCL, estabelecendo as bases para intervenções diagnósticas e terapêuticas subsequentes para CCL.

PURPOSE: This research aims to investigate whether increasing the pension contributions of a firm leads to inefficient investments DESIGN/METHODOLOGY/APPROACH: Based on the 26 135 observations of the Chinese listed firms, this study employs ordinary least squares models to investigate the relationship between pension costs and inefficient investments FINDINGS/RESULTS: This study shows that Chinese listed firms' pension contribution increments result in fewer investment opportunities and a decreased in investment efficiency. This is insignificant for the more profitable firms and state-owned enterprises. It suggests further that a firm's pension cost is significantly associated with its investment inefficiency, particularly for cash flow dominated and financing-restricted firms. This indicates a negative association between pension contributions and cash flows, and several pension contributions may lead to a cash flow shortage in the firms PRACTICAL IMPLICATIONS: For managers, they should improve their investment efficiency within an affordable pension plan; for investors, increasing pension costs potentially decrease their investment returns ORIGINALITY/VALUE: Some findings have reference values for some developing countries

Abstract Introduction: Nutritional status can affect the treatment of hospitalized patients, and Malnutrition can even lead to death. However, the Nutritional status of patients with aplastic anemia (AA) is unclear. Objective: to assess the Nutritional status of aplastic anemia patients with body mass index (BMI) ≥ 24 kg/m2 (high BMI group) and BMI < 24 kg/m2 (low BMI group), and to compare the consistency between different Nutritional screening tools. Methods: patients with aplastic anemia hospitalized from January 2016 to December 2020 were collected. We used the combined index generated by Nutritional Risk Index (NRI), Prognostic Nutritional Index (PNI), Control Nutritional Status (CONUT) and Instant Nutritional Assessment (INA) to assess Nutritional status of patients with aplastic anemia. Kappa index was used to measure the consistency between different Nutritional screening tools. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of different Nutritional screening tools. Results: one hundred and ninety-five patients with aplastic anemia were enrolled. The overall prevalence of Malnutrition calculated by the combined index in patients with aplastic anemia was 51.3 %. The Malnutrition rates of patients in the low BMI group and high BMI group were 60.9 % and 38.8 %, respectively. The Malnutrition rates of very severe aplastic anemia (VSAA) patients, severe aplastic anemia (SAA) patients and ordinary patients were 76 %, 63.8 % and 45.1 %, respectively. Compared with the combined index, NRI had the highest consistency and area under the curve. Conclusions: the Nutritional status of patients with aplastic anemia was very poor; the more serious the disease, the worse the Nutritional status. Although the Malnutrition rate in the low-BMI group was higher than in the high BMI group, the Nutritional status of overweight or obese patients can not be ignored. NRI is the best tool for assessing the Nutritional status of patients with aplastic anemia.

Resumen Introducción: el estado nutricional puede afectar el tratamiento de los pacientes hospitalizados y la malnutrición puede incluso causar la muerte. Sin embargo, el estado nutricional de los pacientes con anemia aplásica (AA) no está claro. Objetivo: evaluar el estado nutricional de pacientes con anemia aplásica con índice de masa corporal (IMC) ≥ 24 kg/m2 (grupo de IMC mayor) e IMC < 24 kg/m2 (grupo de IMC inferior), y comparar la consistencia entre diferentes herramientas de cribado nutricional. Métodos: se recogieron datos de pacientes con anemia aplásica hospitalizados entre enero de 2016 y diciembre de 2020. El estado nutricional de los pacientes con anemia aplásica se evaluó utilizando un índice compuesto por el índice de riesgo nutricional (NRI), el índice de pronóstico nutricional (PNI), el índice de estado nutricional controlado (CONUT) y la evaluación nutricional instantánea (INA). El índice Kappa se utilizó para medir la coherencia entre los diferentes instrumentos de detección nutricional. Las curvas de características operativas de los sujetos (ROC) se utilizaron para evaluar el valor diagnóstico de las diferentes herramientas de detección nutricional. Resultados: un total de 195 pacientes con anemia aplásica fueron incluidos en el estudio. La prevalencia global de desnutrición calculada por el índice combinado en pacientes con anemia aplásica fue del 51,3 %. Las tasas de desnutrición de los pacientes en el grupo de bajo IMC y el grupo de alto IMC fueron 60,9 % y 38,8 %, respectivamente. Las tasas de desnutrición en pacientes con anemia aplásica muy grave (VSAA), anemia aplásica grave (SAA) y pacientes comunes fueron del 76 %, 63,8 % y 45,1 %, respectivamente. En comparación con el índice compuesto, NRI tiene la mayor consistencia y área bajo la curva. Conclusiones: el estado nutricional de los pacientes con anemia aplásica es muy deficiente; a mayor gravedad de la enfermedad, peor estado nutricional. Aunque la tasa de malnutrición en el grupo con bajo IMC es mayor que en el grupo con alto IMC, no se puede pasar por alto el estado nutricional de los pacientes con sobrepeso u obesidad. El NRI es la mejor herramienta para evaluar el estado nutricional de los pacientes con anemia aplásica.

Abstract The AMC-HN-8 cell line and the primary human laryngeal epithelial cell lines were utilized in this work to explore the molecular mechanism of miR-548-3p regulating the gene DAG1 to induce the occurrence and malignant transformation of laryngeal carcinoma. Non-coding RNA miR-548- 3p overexpression plasmid, interference plasmid and blank plasmid were constructed, and the plasmids were transfected into AMC-HN-8 cells, respectively. Meanwhile, a non-transfected plasmid group and a human laryngeal epithelial primary cell group were set up. Five groups of cells were named as NC (Normal control), Model, Ov-miR-548-3p, Sh-miR-548-3p and Blank-plasmid group. The luciferase reporter experiment was used to analyze the regulation characteristics of hsa-miR-548-3p on dystrophin-associated glycoprotein 1 (DAG1). Immunofluorescence was used to analyze the relative expression characteristics of the protein DAG1. The cell cloning experiment was used to analyze the proliferation characteristics of AMC-HN-8. The scratch healing test was used to analyze the migration ability of AMC-HN-8. The transwell test was used to analyze the invasion ability of AMC-HN-8. The RT-PCR was used to analyze the expression level of miR-548-3p. Western blot experiments were used to analyze the expression of protein DAG1, laminin α2 (LAMA2) and utrophin (UTRN). The luciferase report experiment and immunofluorescence test found that the expression of DAG1 and miR-548-3p are positively correlated. Cell cloning, scratching and migration experiments identified that the activity of laryngeal cancer cells was positively correlated with the expression of DAG1. The results of Western blot analysis further strengthened the above conclusions. Through carrying out research on the cellular levels, our work has demonstrated that miR-548-3p regulated the content of protein DAG1, and then further induced malignant transformation of laryngeal carcinoma.

Resumen En este trabajo se utilizaron la línea celular AMC-HN-8 y la línea celular epitelial laríngea humana primaria, para explorar el mecanismo molecular regulador del miR-548-3p sobre el gen DAG1 para inducir la aparición y la transformación maligna del carcinoma laríngeo. Se construyeron el plásmido de sobreexpresión de miR-548-3p de ARN no codificante, el plásmido de interferencia y el plásmido en blanco, y los plásmidos se transfectaron en células AMCHN-8 respectivamente. Mientras tanto, se establecieron un grupo de plásmidos no transfectados y un grupo de células primarias epiteliales laríngeas humanas. Se nombraron cinco grupos de células como NC (control normal), modelo, OvmiR-548-3p, Sh-miR-548-3p y grupo de plásmido en blanco. El experimento indicador de luciferasa se utilizó para analizar las características de regulación de hsa-miR-548-3p en la glicoproteína 1 asociada a distrofina (DAG1). Se utilizó inmunofluorescencia para analizar las características de expresión relativa de la proteína DAG1. El experimento de clonación celular se utilizó para analizar las características de proliferación de AMC-HN-8. Se utilizó la prueba de cicatrización por rascado para analizar la capacidad de migración de AMC-HN-8. La prueba de transwell se utilizó para analizar la capacidad de invasión de AMCHN-8. Se utilizó RT-PCR para analizar el nivel de expresión de miR-548-3p. Se usó un experimento de transferencia Western (Western blot) para analizar las expresiones de la proteína DAG1, laminina α2 (LAMA2) y utrofina (UTRN). El experimento de reporte de luciferasa y la prueba de inmunofluorescencia encontraron que la expresión de DAG1 y miR-548-3p están positivamente correlacionadas. Los experimentos de clonación celular, rascado y migración, identificaron que la actividad de las células cancerosas de laringe se correlacionó positivamente con la expresión de DAG1. Los resultados del análisis de transferencia Western fortalecieron aún más las conclusiones anteriores. A través de la investigación a nivel celular, nuestro proyecto ha demostrado que miR-548-3p regula el contenido de la proteína DAG1 y luego induce la transformación maligna del carcinoma de laringe.

A series of novel betulin-28-hydrazone derivatives (7a-7o) were synthesized. All compounds were evaluated for their in vitro cytotoxicities in four human carcinoma cells (HepG2, MCF-7, HCT-116 and A549). Among them, compound 7l displayed the most potent cytotoxicity with an IC50 (concentration of the tested compound that inhibits 50% of cell growth) value of 7.37 ± 0.38 μM against MCF-7 cells. The preliminary cellular mechanism studies indicated that compound 7l could induce MCF-7 cells apoptosis. The above findings indicated that compound 7l may be used as a lead compound for antitumor agents with improved efficacy.