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INTRODUCTION: Neoadjuvant systemic therapy (NAST) is vital in the management of HER2-positive (HER2+) breast cancer. Nevertheless, the indications for NAST in tumors <2 cm remain controversial. METHOD: A total of 7961 patients were screened from the Surveillance, Epidemiology, and End Result database. Independent prognostic factors were identified using multivariate Cox analysis. Subgroup analyses and Kaplan-Meier analyses were used to simulate whether NAST would provide a survival benefit with different high-risk characteristics. Nomograms were constructed, and an internal validation cohort was employed. RESULTS: Of the 7961 included patients, 1137 (14.3%) underwent NAST. In the total population, NAST was associated with poorer overall survival (OS) and breast cancer-specific survival (BCSS) (OS: P = 0.00093; BCSS: P  <  0.0001). Multivariate Cox analysis confirmed that NAST markedly affected the prognosis of enrolled patients. Besides, a direct association between T, N, age, subtype, and prognosis was observed. Subgroup analyses yielded in these three subgroups, T1c, hormone receptor-negative, and 61-69 years of age, NAST and AST had comparable OS, while NAST possessed worse BCSS. Notably, even in the N3, we still did not observe any additional benefit of NAST. The calculated C-index of 0.72 and 0.73 confirmed the predictability of the nomograms. The AUCs exhibit consistency in the training and validation cohorts. CONCLUSION: Our findings suggest that NAST does not provide additional benefit to patients with T1 HER2+ breast cancer, even in the presence of lymph node metastasis, T1c, or hormone receptor negativity. This study facilitates the implementation of individualized management strategies.

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Regulation of histone proteins affects gene expression through multiple mechanisms including exchange with histone variants. However, widely expressed variants of H2B remain elusive. Recent findings link histone variants to neurological disorders, yet few are well studied in the brain. We applied new tools including novel antibodies, biochemical assays, and sequencing approaches to reveal broad expression of the H2B variant H2BE, and defined its role in regulating chromatin structure, neuronal transcription, and mouse behavior. We find that H2BE is enriched at promoters and a single unique amino acid allows it to dramatically enhance chromatin accessibility. Lastly, we show that H2BE is critical for synaptic gene expression and long-term memory. Together, these data reveal a novel mechanism linking histone variants to chromatin regulation, neuronal function, and memory. This work further identifies the first widely expressed H2B variant and uncovers a single histone amino acid with profound effects on genomic structure.

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Abstract We aimed to compare the effects of oxycodone hydrochloride and dezocine on hemodynamics and inflammatory factors in patients receiving gynecological laparoscopic surgery under general anesthesia. A total of 246 patients were divided into group A and B (n=123). Hemorheology indices were recorded 5 min after anesthesia (T0), 1 min after pneumoperitoneum (T1), when position was changed 5 min after pneumoperitoneum (T2), 15 min after pneumoperitoneum (T3), 1 min (T4) and 5 min (T5) after position was restored. Visual analogue scale scores 1, 2, 6, 12, 24 and 48 h after operation were recorded. Postoperative adverse reactions and visceral pain were observed. The expression levels of inflammatory factors were detected by enzyme-linked immunosorbent assay 12 h after operation. Compared with group A, group B had higher heart rate and mean arterial pressure at T2, lower central venous pressure and cardiac output at T1-T3, and higher systemic vascular resistance at T1-T5 (P<0.05). The incidence rate of pain syndrome in group A was lower (P<0.05). Group A had lower tumor necrosis factor-alpha and interleukin-6 expression levels and higher interleukin-10 level than those of group B (P<0.05). For gynecological laparoscopic surgery, oxycodone preemptive analgesia has superior outcomes to those of dezocine

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ABSTRACT Introduction: With the growing importance of physical training over sport training for competition, more research has been conducted. One of the least explored techniques is superisometric aquatic training. Objective: Study the application of super-isometric aquatic training to the physical training of soccer athletes. Methods: A literature review was performed to elaborate an experimental protocol. The experimental method was conducted on 24 university volunteers randomly divided into control and experimental groups. Classical training was conducted for two weeks between the groups, superisometric aquatic training was added only in the experimental group. Through the mathematical-statistical method, a comparative analysis of the research results was elaborated, and the effects of the intervention were discussed. Results: The movement time of the athletes in the experimental training group was reduced by 1.89s. The performance of running, tapping, standing jump, and weightlifting tests is not significantly different from those of the traditional strength training group. Conclusion: The application of superisometric aquatic training in the physical preparation of soccer players increased the overall strength of athletes,and also beneficially influenced specific activities of the sport. It is recommended to analyze the characteristics of the athlete and integrate superisometric training to general strength traispecificcally to the need of each athlete. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: Com a crescente importância do treinamento físico sobre o treinamento esportivo para competição, um número cada vez maior de pesquisas vem sendo realizado. Uma das técnicas pouco exploradas é o treinamento aquático superisométrico. Objetivo: Estudar a aplicação do treinamento aquático superisométrico ao treinamento físico de preparo dos atletas de futebol. Métodos: Uma análise da literatura foi efetuada para elaborar um protocolo experimental. O método experimental foi conduzido sobre 24 universitários voluntários divididos aleatoriamente em grupo controle e experimental. O treinamento clássico foi conduzido por duas semanas entre os grupos, o treinamento aquático superisométrico foi adicionado apenas no grupo experimental. Através do método estatístico matemático uma análise comparativa dos resultados da pesquisa foi elaborada e os efeitos da intervenção foram discutidos. Resultados: O tempo de movimento dos atletas no grupo de treinamento experimental foi reduzido em 1,89s. O desempenho de corrida, toque, salto em pé e os resultados dos testes de levantamento de peso não foram significativamente diferentes daqueles do grupo de treinamento de força tradicional. Conclusão: A aplicação do treinamento aquático superisométrico no preparo físico de futebolistas aumentou a força geral dos atletas, também influenciou beneficamente em atividades específicas do esporte. Recomenda-se analisar as características do esportista e integrar o treinamento superisométrico ao treinamento de força geral especificamente à necessidade de cada esportista. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: Con la creciente importancia de la preparación física en el entrenamiento deportivo para la competición, se ha realizado un número cada vez mayor de investigaciones. Una de las técnicas poco exploradas es el entrenamiento acuático superisométrico. Objetivo: Estudiar la aplicación del entrenamiento acuático superisométrico a la preparación física de los deportistas de fútbol. Métodos: Se realizó una revisión de la literatura para elaborar un protocolo experimental. El método experimental se llevó a cabo con 24 voluntarios universitarios divididos aleatoriamente en grupos de control y experimentales. El entrenamiento clásico se realizó durante quince días entre los grupos, el entrenamiento acuático superisométrico se añadió sólo en el grupo experimental. Mediante el método estadístico matemático se elaboró un análisis comparativo de los resultados de la investigación y se discutieron los efectos de la intervención. Resultados: El tiempo de movimiento de los atletas del grupo de entrenamiento experimental se redujo en 1,89s. El rendimiento de la carrera, el golpeo, el salto de pie y los resultados de las pruebas de levantamiento de pesas no fueron significativamente diferentes de los del grupo de entrenamiento de fuerza tradicional. Conclusión: La aplicación del entrenamiento acuático superisométrico en la preparación física de los jugadores de fútbol aumentó la fuerza general de los atletas, también influyó beneficiosamente en las actividades específicas del deporte. Se recomienda analizar las características del deportista e integrar el entrenamiento superisométrico al entrenamiento de fuerza general de forma específica a la necesidad de cada deportista. Nivel de evidencia II; Estudios terapéuticos -investigación de los resultados del tratamiento.

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ABSTRACT Objective: Interstitial cystitis (IC)/bladder pain syndrome (BPS) is a chronic inflammatory disease that can cause bladder pain and accompanying symptoms, such as long-term urinary frequency and urgency. IC/BPS can be ulcerative or non-ulcerative. The aim of this study was to explore the core genes involved in the pathogenesis of ulcerative IC, and thus the potential biomarkers for clinical treatment. Materials and Methods: First, the gene expression dataset GSE11783 was downloaded using the Gene Expression Omnibus (GEO) database and analyzed using the limma package in R to identify differentially expressed genes (DEGs). Then, the Database for Annotation, Visualization and Integrated Discovery (DAVID) was used for Gene Ontology (GO) functional analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) was used for pathway enrichment analysis. Finally, the protein-protein interaction (PPI) network was constructed, and key modules and hub genes were determined using the STRING and Cytoscape software. The resulting key modules were then analyzed for tissue-specific gene expression using BioGPS. Results: A total of 216 up-regulated DEGs and 267 down-regulated genes were identified, and three key modules and nine hub genes were obtained. Conclusion: The core genes (CXCL8, CXCL1, IL6) obtained in this study may be potential biomarkers of interstitial cystitis with guiding significance for clinical treatment.

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OBJECTIVE: Interstitial cystitis (IC)/bladder pain syndrome (BPS) is a chronic inflammatory disease that can cause bladder pain and accompanying symptoms, such as long-term urinary frequency and urgency. IC/BPS can be ulcerative or non-ulcerative. The aim of this study was to explore the core genes involved in the pathogenesis of ulcerative IC, and thus the potential biomarkers for clinical treatment. MATERIALS AND METHODS: First, the gene expression dataset GSE11783 was downloaded using the Gene Expression Omnibus (GEO) database and analyzed using the limma package in R to identify differentially expressed genes (DEGs). Then, the Database for Annotation, Visualization and Integrated Discovery (DAVID) was used for Gene Ontology (GO) functional analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) was used for pathway enrichment analysis. Finally, the protein-protein interaction (PPI) network was constructed, and key modules and hub genes were determined using the STRING and Cytoscape software. The resulting key modules were then analyzed for tissue-specific gene expression using BioGPS. RESULTS: A total of 216 up-regulated DEGs and 267 down-regulated genes were identified, and three key modules and nine hub genes were obtained. CONCLUSION: The core genes (CXCL8, CXCL1, IL6) obtained in this study may be potential biomarkers of interstitial cystitis with guiding significance for clinical treatment.

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Epoxide hydrolases (EHs) are present in all living organisms and catalyze the hydrolysis of epoxides to the corresponding vicinal diols. EH are involved in the metabolism of endogenous and exogenous epoxides, and thus have application in pharmacology and biotechnology. In this work, we describe the substrates and inhibitors selectivity of an epoxide hydrolase recently cloned from the filamentous fungus Trichoderma reesei QM9414 (TrEH). We also studied the TrEH urea-based inhibitors effects in the fungal growth. TrEH showed high activity on radioative and fluorescent surrogate and natural substrates, especially epoxides from docosahexaenoic acid. Using a fluorescent surrogate substrate, potent inhibitors of TrEH were identified. Interestingly, one of the best compounds inhibit up to 60% of T. reesei growth, indicating an endogenous role for TrEH. These data make TrEH very attractive for future studies about fungal metabolism of fatty acids and possible development of novel drugs for human diseases.

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