Clinical features and next-generation sequencing landscape of essential thrombocythemia, prefibrotic primary myelofibrosis, and overt fibrotic primary myelofibrosis: a Chinese monocentric retrospective study.

OBJECTIVE: Since prefibrotic primary myelofibrosis (pre-PMF) was recognized as a separate entity in the 2016 revised classification of MPN differed from essential thrombocythemia (ET) or overt fibrotic primary myelofibrosis (overt PMF), it has been a subject of debate among experts due to its indefinite diagnosis. METHODS: We retrospectively reviewed the clinical parameters, haematologic information, and genetic mutations of patients who were diagnosed with myeloproliferative neoplasms (MPNs) according to the WHO 2016 criteria in China, including 56 ET patients, 19 pre-PMF patients, and 43 overt PMF patients. RESULTS: Pre-PMF patients exhibited higher leukocyte counts [14.2(6.0-28.1) × 109/L vs 9.6(4.0-55.0) × 109/L, P = 0.003], LDH values [307(233-479)U/L vs 241(129-1182)U/L, P < 0.001], onset ages [67(32-76) years vs 50(16-79) years, P = 0.006], a higher frequency of splenomegaly(47.4% vs 16.7%, P = 0.018) and hypertension (57.9 vs 23.2%, P = 0.005) than ET patients. On the other hand, pre-PMF patients had higher platelet counts [960(500-2245) × 109/L vs 633(102-1720) × 109/L, P = 0.017], haemoglobin levels [152(115-174)g/L vs 119(71-200)g/L, P = 0.003], lower LDH values [307(233-479)U/L vs 439(134-8100)U/L, P = 0.007] and a lower frequency of splenomegaly(47.4 vs 75.6%, P = 0.031) than overt PMF patients. Next-generation sequencing landscape was performed in 50 patients, revealed the frequency of EP300 mutations was significantly increased in pre-PMF patients compared with ET and overt PMF patients (60 vs 10 vs 15.79%, P = 0.033), and WT1 was more often overexpressed (WT1/ABL1 copies ≥ 1.0%) in patients with overt PMF than in those with ET or pre-PMF(54.55 vs 16.67 vs 17.65%, P = 0.009). In terms of outcome, male sex, along with symptoms including MPN10, anaemia (haemoglobin < 120 g/L), thrombocytopenia (platelet count < 100 × 109/L), leucocytosis (leukocyte counts > 13 × 109/L), high LDH value (> 350U/L), splenomegaly, WT1 overexpression(WT1/ABL1 copies ≥ 1.0%), KMT2A, ASXL1 and TP53 mutations, indicated a poor prognosis for PMF patients. CONCLUSION: The results of this study indicated that a comprehensive evaluation of BM features, clinical phenotypes, haematologic parameters, and molecular profiles is needed for the accurate diagnosis and treatment of ET, pre-PMF, and overt PMF patients.

Posture optimization in swimming based on sports mechanics / Otimização da postura na natação baseada na mecânica esportiva / Optimización de la postura en la natación basada en la mecánica deportiva

ABSTRACT Introduction Speed and posture are two determining factors for the success of swimmers. Posture optimization can make athletes' actions more standardized and improve their speed at a competitive level. Objective Explore the optimization of swimming posture based on sports mechanics. Methods In the controlled experiment, the control group was given routine training, while the experimental group was given sport mechanics-based swimming posture optimization training. A duration of 60 minutes daily, three times a week. The experiment was completed in 6 weeks. Data by computerized cinematography were extracted using the reflective marking ball technique. Its mechanical motion and time consumption characteristics were collected before and after the experiment, cataloged, compared, and discussed statistically. Results Daily and posture optimization training can improve athletes' body extension range. The effect of the experimental group in improving the range of body extension was shown to be greater than the standard training and slightly greater than the daily training by shortening the action time. Conclusion The posture optimization scheme for swimming based on sports mechanics can improve athletes' extension range and speed. Physical education teachers and coaches should further optimize and promote the swimming posture optimization scheme to improve the performance of their athletes. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução Velocidade e postura são dois fatores determinantes para o sucesso dos nadadores. A otimização da postura pode não apenas tornar as ações dos atletas mais padronizadas como também pode melhorar a sua velocidade em um nível competitivo. Objetivo Explorar a otimização da postura de natação baseada na mecânica esportiva. Métodos No experimento controlado, o grupo de controle efetuou o treinamento de rotina, enquanto ao grupo experimental foi adicionado o treinamento de otimização da postura de natação baseado na mecânica esportiva. Numa duração de 60 minutos diários, três vezes por semana, o experimento foi completado em 6 semanas. Dados por cinematografia computadorizada foram extraídos utilizando a técnica da bola refletiva de marcação. Suas características mecânicas de movimento e características de consumo de tempo foram coletadas antes e depois do experimento, catalogadas, comparadas e discutidas estatisticamente. Resultados Tanto o treinamento diário quanto o treinamento de otimização da postura podem melhorar o alcance da extensão corporal dos atletas. O efeito do grupo experimental em melhorar o alcance da extensão corporal demonstrou-se superior ao do treinamento padrão, sendo ligeiramente maior do que o do treinamento diário encurtando o tempo de ação. Conclusão O esquema de otimização da postura para natação baseado na mecânica esportiva pode efetivamente melhorar a faixa de extensão e a velocidade dos atletas. Os professores e treinadores de educação física devem otimizar e promover ainda mais o esquema de otimização da postura de natação, visando melhorar o desempenho de seus esportistas. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción La velocidad y la postura son dos factores determinantes para el éxito de los nadadores. La optimización de la postura no sólo puede hacer que las acciones de los atletas sean más estandarizadas, sino que también puede mejorar su velocidad a nivel competitivo. Objetivo Explorar la optimización de la postura de natación basada en la mecánica deportiva. Métodos En el experimento controlado, el grupo de control realizó un entrenamiento rutinario, mientras que al grupo experimental se le añadió un entrenamiento de optimización de la postura de natación basado en la mecánica deportiva. Con una duración de 60 minutos diarios, tres veces por semana, el experimento se completó en 6 semanas. Los datos de la cinematografía computarizada se extrajeron mediante la técnica de la bola de marcado reflectante. Sus características de movimiento mecánico y de consumo de tiempo fueron recogidas antes y después del experimento, catalogadas, comparadas y discutidas estadísticamente. Resultados Tanto el entrenamiento diario como el de optimización de la postura pueden mejorar el rango de extensión corporal de los atletas. El efecto del grupo experimental en la mejora del rango de extensión corporal se mostró superior al entrenamiento estándar, y ligeramente superior al entrenamiento diario al acortar el tiempo de acción. Conclusión El esquema de optimización de la postura para la natación basado en la mecánica deportiva puede mejorar eficazmente el rango de extensión y la velocidad de los atletas. Los profesores de educación física y los entrenadores deben seguir perfeccionando y promoviendo el esquema de optimización de la postura de natación para mejorar el rendimiento de sus deportistas. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

The mechanisms and cross-protection of trained innate immunity.

In recent years, the traditional cognition of immunological memory being specific to adaptive immunity has been challenged. Innate immunity can mount enhanced responsiveness upon secondary stimulation, and a phenomenon is termed trained innate immunity. Trained innate immunity is orchestrated by distinct metabolic and epigenetic reprogramming in both circulating myeloid cells and myeloid progenitor cells in bone marrow, leading to long-term resistance to related and non-related pathogens infections. The induction of trained innate immunity can also polarize innate immune cells towards a hyperresponsive phenotype in the tumor microenvironment to exert antitumor effects. This review will discuss the current understanding of innate immune memory and the mechanisms during the induction of innate immunity, including signaling pathways, metabolic changes, and epigenetic rewriting. We also provide an overview of cross-protection against infectious diseases and cancers based on trained innate immunity.

Targeted Next-Generation Sequencing Identifies Additional Mutations Other than BCR∷ABL in Chronic Myeloid Leukemia Patients: A Chinese Monocentric Retrospective Study.

A proportion of patients with somatic variants show resistance or intolerance to TKI therapy, indicating additional mutations other than BCR∷ABL1 may lead to TKI treatment failure or disease progression. We retrospectively evaluated 151 CML patients receiving TKI therapy and performed next-generation sequencing (NGS) analysis of 22 CML patients at diagnosis to explore the mutation spectrum other than BCR∷ABL1 affecting the achievement of molecular responses. The most frequently mutated gene was ASXL1 (40.9%). NOTCH3 and RELN mutations were only carried by subjects failing to achieve a major molecular response (MMR) at 12 months. The distribution frequency of ASXL1 mutations was higher in the group that did not achieve MR4.0 at 36 months (p = 0.023). The achievement of MR4.5 at 12 months was adversely impacted by the presence of >2 gene mutations (p = 0.024). In the analysis of clinical characteristics, hemoglobin concentration (HB) and MMR were independent factors for deep molecular response (DMR), and initial 2GTKI therapy was better than 1GTKI in the achievement of molecular response. For the scoring system, we found the ELTS score was the best for predicting the efficacy of TKI therapy and the Socal score was the best for predicting mutations other than BCR∷ABL.

Worldwide cancer statistics of adults over 75 years old in 2019: a systematic analysis of the global burden of disease study 2019.

BACKGROUND AND PURPOSE: Cancer has become one of the major killers of humanity due to the number of people over the age of 75 increasing with population ageing. The aim of this study was to analyse the incidence and mortality rates in people over 75 of 29 cancer types in 204 countries and regions, as well as the trends from 1990 to 2019. METHODS: Twenty-nine cancer types were collected from the Global Burden of Disease (GBD) 2019 database( https://vizhub.healthdata.org/gbd-results/ ). We collected global cancer data for 2019 in terms of sex, age, sociodemographic index (SDI), region, etc. The estimated annual percentage change (EAPC) was calculated to assess the trend of the cancer incidence and mortality rate from 1990 to 2019. RESULTS: In 2019, the number of new cancer cases and deaths among people 75 and older was almost 3 and 4.5 times that of 1990, respectively. From 1990 to 2019, there was a slow rise in incidence and a slight decline in mortality. There were significant differences in the cancer burden based on sex, age, region, and SDI. The cancer burden in men was higher than in women. In addition, the cancer burden varied from region to region. The highest cancer burden occurred in high-income North America. In addition, the higher the SDI was, the greater the burden of cancer. The incidence of cancer in high SDI was approximately seven times that of low SDI, and the trend of increase in high SDI was obvious. However, the trend of mortality in high SDI was decreasing, while it was increasing in low SDI. CONCLUSIONS: The present study focused on the cancer burden in adults over 75 years old. The findings in the study could serve as the basis for an analysis of the types of cancers that are most prevalent in different regions. This is beneficial for strategies of prevention and treatment according to the characteristics of different countries and regions to reduce the burden of cancer in older adults.