Mechanisms of brain damage caused by inorganic fluoride using proteomics-based techniques / 环境与职业医学

Background Chronic excessive exposure to fluoride can cause damage to the central nervous system and a certain degree of learning and memory impairment. However, the associated mechanism is not yet clear and further exploration is needed. Objective Using 4D unlabelled quantitative proteomics techniques to explore differentially expressed proteins and their potential mechanisms of action in chronic excessive fluoride exposure induced brain injury. Methods Twenty-four SPF-grade adult SD rats, half male and half male, were selected and divided into a control group and a fluoride group by random number table method, with 12 rats in each group. Among them, the control group drank tap water (fluorine content<1 mg·L−1), the fluoride group drank sodium fluoride solution (fluorine content 10 mg·L−1), and both groups were fed with ordinary mouse feed (fluoride content<0.6 mg·kg−1). After 180 d of feeding, the SD rats were weighed, and then part of the brain tissue was sampled for pathological examination by hematoxylin-eosin (HE) staining and Nissl staining. The rest of the brain tissue was frozen and stored at −80 ℃. Three brain tissue samples from each group were randomly selected for proteomics detection. Differentially expressed proteins were screened and subcellular localization analysis was performed, followed by Gene Ontology (GO) function analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, cluster analysis, and protein-protein interaction analysis. Finally, Western blotting was used to detect the expression levels of key proteins extracted from the brain tissue samples. Results After 180 d of feeding, the average weight of the rats in the fluoride group was significantly lower than that in the control group (P<0.05). The brain tissue stained with HE showed no significant morphological changes in the cerebral cortex of the fluoride treated rats, and neuron loss, irregular arrangement of neurons, eosinophilic changes, and cell body pyknosis were observed in the hippocampus. The Nissl staining results showed that the staining of neurons in the cerebral cortex and hippocampus of rats exposed to fluoride decreased (Nissl bodies decreased). The proteomics results showed that a total of 6927 proteins were identified. After screening, 206 differentially expressed proteins were obtained between the control group and the fluoride group, including 96 up-regulated proteins and 110 down-regulated proteins. The differential proteins were mainly located in cytoplasm (30.6%), nucleus (27.2%), mitochondria (13.6%), plasma membrane (13.6%), and extracellular domain (11.7%). The GO analysis results showed that differentially expressed proteins mainly participated in biological processes such as iron ion transport, regulation of dopamine neuron differentiation, and negative regulation of respiratory burst in inflammatory response, exercised molecular functions such as ferrous binding, iron oxidase activity, and cytokine activity, and were located in the smooth endoplasmic reticulum membrane, fixed components of the membrane, chloride channel complexes, and other cellular components. The KEGG significantly enriched pathways included biosynthesis of secondary metabolites, carbon metabolism, and microbial metabolism in diverse environments. The results of differential protein-protein interaction analysis showed that the highest connectivity was found in glucose-6-phosphate isomerase (Gpi). The expression level of Gpi in the brain tissue of the rats in the fluoride group was lower than that in the control group by Western blotting (P<0.05). Conclusion Multiple differentially expressed proteins are present in the brain tissue of rats with chronic fluorosis, and their functions are related to biosynthesis of secondary metabolites, carbon metabolism, and microbial metabolism in diverse environments; Gpi may be involved in cerebral neurological damage caused by chronic overdose fluoride exposure.

Directrices para presentación de informes de ensayos clínicos sobre intervenciones con inteligencia artificial: extensión CONSORT-AI / Reporting guidelines for clinical trial reports for interventions involving artificial intelligence: the CONSORT-AI extension / Diretrizes para relatórios de ensaios clínicos com intervenções que utilizam inteligência artificial: a extensão CONSORT-AI

resumen está disponible en el texto completo

ABSTRACT The CONSORT 2010 statement provides minimum guidelines for reporting randomized trials. Its widespread use has been instrumental in ensuring transparency in the evaluation of new interventions. More recently, there has been a growing recognition that interventions involving artificial intelligence (AI) need to undergo rigorous, prospective evaluation to demonstrate impact on health outcomes. The CONSORT-AI (Consolidated Standards of Reporting Trials-Artificial Intelligence) extension is a new reporting guideline for clinical trials evaluating interventions with an AI component. It was developed in parallel with its companion statement for clinical trial protocols: SPIRIT-AI (Standard Protocol Items: Recommendations for Interventional Trials-Artificial Intelligence). Both guidelines were developed through a staged consensus process involving literature review and expert consultation to generate 29 candidate items, which were assessed by an international multi-stakeholder group in a two-stage Delphi survey (103 stakeholders), agreed upon in a two-day consensus meeting (31 stakeholders) and refined through a checklist pilot (34 participants). The CONSORT-AI extension includes 14 new items that were considered sufficiently important for AI interventions that they should be routinely reported in addition to the core CONSORT 2010 items. CONSORT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention is integrated, the handling of inputs and outputs of the AI intervention, the human-AI interaction and provision of an analysis of error cases. CONSORT-AI will help promote transparency and completeness in reporting clinical trials for AI interventions. It will assist editors and peer reviewers, as well as the general readership, to understand, interpret and critically appraise the quality of clinical trial design and risk of bias in the reported outcomes.

RESUMO A declaração CONSORT 2010 apresenta diretrizes mínimas para relatórios de ensaios clínicos randomizados. Seu uso generalizado tem sido fundamental para garantir a transparência na avaliação de novas intervenções. Recentemente, tem-se reconhecido cada vez mais que intervenções que incluem inteligência artificial (IA) precisam ser submetidas a uma avaliação rigorosa e prospectiva para demonstrar seus impactos sobre os resultados de saúde. A extensão CONSORT-AI (Consolidated Standards of Reporting Trials - Artificial Intelligence) é uma nova diretriz para relatórios de ensaios clínicos que avaliam intervenções com um componente de IA. Ela foi desenvolvida em paralelo à sua declaração complementar para protocolos de ensaios clínicos, a SPIRIT-AI (Standard Protocol Items: Recommendations for Interventional Trials - Artificial Intelligence). Ambas as diretrizes foram desenvolvidas por meio de um processo de consenso em etapas que incluiu revisão da literatura e consultas a especialistas para gerar 29 itens candidatos. Foram feitas consultas sobre esses itens a um grupo internacional composto por 103 interessados diretos, que participaram de uma pesquisa Delphi em duas etapas. Chegou-se a um acordo sobre os itens em uma reunião de consenso que incluiu 31 interessados diretos, e os itens foram refinados por meio de uma lista de verificação piloto que envolveu 34 participantes. A extensão CONSORT-AI inclui 14 itens novos que, devido à sua importância para as intervenções de IA, devem ser informados rotineiramente juntamente com os itens básicos da CONSORT 2010. A CONSORT-AI preconiza que os pesquisadores descrevam claramente a intervenção de IA, incluindo instruções e as habilidades necessárias para seu uso, o contexto no qual a intervenção de IA está inserida, considerações sobre o manuseio dos dados de entrada e saída da intervenção de IA, a interação humano-IA e uma análise dos casos de erro. A CONSORT-AI ajudará a promover a transparência e a integralidade nos relatórios de ensaios clínicos com intervenções que utilizam IA. Seu uso ajudará editores e revisores, bem como leitores em geral, a entender, interpretar e avaliar criticamente a qualidade do desenho do ensaio clínico e o risco de viés nos resultados relatados.

Directrices para los protocolos de ensayos clínicos de intervenciones con inteligencia artificial: la extensión SPIRIT-AI / Guidelines for clinical trial protocols for interventions involving artificial intelligence: the SPIRIT-AI extension / Diretrizes para protocolos de ensaios clínicos com intervenções que utilizam inteligência artificial: a extensão SPIRIT-AI

resumen está disponible en el texto completo

ABSTRACT The SPIRIT 2013 statement aims to improve the completeness of clinical trial protocol reporting by providing evidence-based recommendations for the minimum set of items to be addressed. This guidance has been instrumental in promoting transparent evaluation of new interventions. More recently, there has been a growing recognition that interventions involving artificial intelligence (AI) need to undergo rigorous, prospective evaluation to demonstrate their impact on health outcomes. The SPIRIT-AI (Standard Protocol Items: Recommendations for Interventional Trials-Artificial Intelligence) extension is a new reporting guideline for clinical trial protocols evaluating interventions with an AI component. It was developed in parallel with its companion statement for trial reports: CONSORT-AI (Consolidated Standards of Reporting Trials-Artificial Intelligence). Both guidelines were developed through a staged consensus process involving literature review and expert consultation to generate 26 candidate items, which were consulted upon by an international multi-stakeholder group in a two-stage Delphi survey (103 stakeholders), agreed upon in a consensus meeting (31 stakeholders) and refined through a checklist pilot (34 participants). The SPIRIT-AI extension includes 15 new items that were considered sufficiently important for clinical trial protocols of AI interventions. These new items should be routinely reported in addition to the core SPIRIT 2013 items. SPIRIT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention will be integrated, considerations for the handling of input and output data, the human-AI interaction and analysis of error cases. SPIRIT-AI will help promote transparency and completeness for clinical trial protocols for AI interventions. Its use will assist editors and peer reviewers, as well as the general readership, to understand, interpret and critically appraise the design and risk of bias for a planned clinical trial.

RESUMO A declaração SPIRIT 2013 tem como objetivo melhorar a integralidade dos relatórios dos protocolos de ensaios clínicos, fornecendo recomendações baseadas em evidências para o conjunto mínimo de itens que devem ser abordados. Essas orientações têm sido fundamentais para promover uma avaliação transparente de novas intervenções. Recentemente, tem-se reconhecido cada vez mais que intervenções que incluem inteligência artificial (IA) precisam ser submetidas a uma avaliação rigorosa e prospectiva para demonstrar seus impactos sobre os resultados de saúde. A extensão SPIRIT-AI (Standard Protocol Items: Recommendations for Interventional Trials - Artificial Intelligence) é uma nova diretriz de relatório para protocolos de ensaios clínicos que avaliam intervenções com um componente de IA. Essa diretriz foi desenvolvida em paralelo à sua declaração complementar para relatórios de ensaios clínicos, CONSORT-AI (Consolidated Standards of Reporting Trials - Artificial Intelligence). Ambas as diretrizes foram desenvolvidas por meio de um processo de consenso em etapas que incluiu revisão da literatura e consultas a especialistas para gerar 26 itens candidatos. Foram feitas consultas sobre esses itens a um grupo internacional composto por 103 interessados diretos, que participaram de uma pesquisa Delphi em duas etapas. Chegou-se a um acordo sobre os itens em uma reunião de consenso que incluiu 31 interessados diretos, e os itens foram refinados por meio de uma lista de verificação piloto que envolveu 34 participantes. A extensão SPIRIT-AI inclui 15 itens novos que foram considerados suficientemente importantes para os protocolos de ensaios clínicos com intervenções que utilizam IA. Esses itens novos devem constar dos relatórios de rotina, juntamente com os itens básicos da SPIRIT 2013. A SPIRIT-AI preconiza que os pesquisadores descrevam claramente a intervenção de IA, incluindo instruções e as habilidades necessárias para seu uso, o contexto no qual a intervenção de IA será integrada, considerações sobre o manuseio dos dados de entrada e saída, a interação humano-IA e a análise de casos de erro. A SPIRIT-AI ajudará a promover a transparência e a integralidade nos protocolos de ensaios clínicos com intervenções que utilizam IA. Seu uso ajudará editores e revisores, bem como leitores em geral, a entender, interpretar e avaliar criticamente o delineamento e o risco de viés de um futuro estudo clínico.

Prevalence and Intensity of Dental Caries in School-age Children of the Krasnoyarsk Territory.

Introduction: The high level of prevalence and intensity of dental caries in school children reflects the urgency of the problem and the necessity of proper dental education among children and their parents and to develop recommendations aimed at the prevention of dental caries. Aim: To find out the epidemiological situation of dental caries in school age children of Krasnoyarsk Territory. Materials and Methods: A study was conducted on the prevalence and intensity of dental caries in 232 school-age children of educational institutions in the city of Norilsk, Krasnoyarsk Krai and 386 children in the city of Talnakh aged 7 to 17 years. The study used a special dental examination card recommended by WHO (2013). Results: The results obtained characterize an unfavorable level of morbidity with a high level of dental treatment needs and preventive care. School children and their parents exhibited low level of knowledge pertaining to sanitary conditions. The situation dictates the need for further intensification of the prevention of dental diseases and sanitary and educational work among the population. Conclusion: The research showed the inimical epidemiological situation of dental caries in school-age children of the Krasnoyarsk Territory. The situation dictates the need for further intensification of sanitary and educational work and the introduction of an interdepartmental program for the prevention of dental caries in the region.

Escherichia coli productora de toxina Shiga: el desafío de adherirse para sobrevivir / Shiga toxin producing Escherichia coli: the challenge of adherence to survive

Resumen Las cepas de Escherichia coli productoras de toxina Shiga (STEC) son reconocidas como responsables de un alto número de casos de enfermedades de transmisión alimentaria a nivel mundial. Su patogenicidad ha sido vinculada directamente con la actividad de las toxinas (Stx); sin embargo, la habilidad de estas bacterias para colonizar al huésped y otras superficies puede ser esencial para desarrollar su poder patogénico. La gran plasticidad genómica de cepas STEC se infiere de la variabilidad de perfiles de virulencia, con la frecuente emergencia de cepas con nuevos genes, codificados en nuevas islas de patogenicidad vinculadas al metabolismo y la adherencia. La formación de biofilm es un mecanismo espontáneo por el cual las cepas STEC resisten en un ambiente hostil, lo que les permite sobrevivir y, de esa forma, llegar al huésped, a través de los alimentos o de las superficies que están en contacto con ellos. Este mecanismo presenta una alta variabilidad intra e interserotipo y su desarrollo no depende solo de los microorganismos que lo conforman. Factores inherentes al ambiente (pH, temperatura) y la superficie (acero inoxidable, poliestireno) a la que pueden adherirse influyen en la expresión de biofilm. El concepto «una salud¼ implica la interrelación entre los actores de salud pública, animal y ambiental para lograr alimentos inocuos y evitar contaminación cruzada y resistencia a sanitizantes, lo cual pone de manifiesto la necesidad de identificar patógenos emergentes a través de nuevos marcadores moleculares, que detecten cepas STEC portadoras del denominado locus for enterocyte effacement (LEE) o del locus de adherencia y autoagregación (LAA).

Abstract Shiga Toxin-producing Escherichia coli (STEC) is recognized as being responsible for a large number of foodborne illnesses around the world. The pathogenicity of STEC has been related to Stx toxins. However, the ability of STEC to colonize the host and other surfaces can be essential for developing its pathogenicity. Different virulence profiles detected in STEC could cause the emergence of strains carrying new genes codified in new pathogenicity islands linked to metabolism and adherence. Biofilm formation is a spontaneous mechanism whereby STEC strains resist in a hostile environment being able to survive and consequently infect the host through contaminated food and food contact surfaces. Biofilm formation shows intra-and inter-serotype variability, and its formation does not depend only on the microorganisms involved. Other factors related to the environment (such as pH, temperature) and the surface (stainless steel and polystyrene) influence biofilm expression. The «One Health¼ concept implies the interrelation between public, animal, and environmental health actors to ensure food safety, prevent cross-contamination and resistance to sanitizers, highlighting the need to identify emerging pathogens through new molecular markers of rapid detection that involve STEC strains carrying the Locus of Enterocyte Effacement or Locus of Adhesion and Autoaggregation.

The Chinese patent medicine Tongfengding capsule for gout in adults: a systematic review of safety and effectiveness

Abstract Background Gout is a common inflammatory arthritis caused by increased serum uric acid levels. Untreated or insufficiently treated gout can lead to deposition of monosodium urate crystals in joints, cartilage, and kidneys. Although Tongfengding capsules, a Chinese patent medicine, have long been used to treat gout, their effects and safety have not been reviewed systematically. This study evaluated its efficacy and safety for gout in adults. Methods Randomized controlled trials involving Tongfengding capsule for gout in adults were searched from PubMed, EMBASE, Cochrane Central Register of Controlled Trials, CBM, CNKI, and VIP databases, and analyzed using the Cochrane Handbook criteria. The primary outcome measures were the total effective rate. The secondary outcome measures including the blood uric acid (BUA), 24-h urinary total protein (24-h UTP), blood urea nitrogen (BUN), interleukin (IL)-6, IL-8, tumor necrosis factor-alpha (TNF-α) and adverse effects. The risk of bias was evaluated in all included studies. RevMan ver. 5.3.5 and GRADE profiler was used for data analysis and assessing the quality of evidence, respectively. Results Six studies (n = 607 Chinese participants) were included. Tongfengding capsules plus conventional treatment significantly increased the total effective rate (RR 1.21, 95% CI 1.11-1.33), while reducing the BUA (MD − 66.05 μmol/L, 95% CI − 81.26 to − 50.84), 24-h UTP (MD − 0.83 g/24 h, 95% CI − 0.96 to − 0.70), BUN (MD − 0.90 mmol/L, 95% CI − 1.60 to − 0.20), IL-6 (MD − 6.99 ng/L, 95% CI − 13.22 to − 0.75), IL-8 (MD − 12.17 ng/L, 95% CI − 18.07 to − 6.27), TNF-α (MD − 8.50 ng/L, 95% CI − 15.50 to − 1.51), and adverse effects (RR 0.21, 95% CI 0.04-0.95). Conclusion Tongfengding capsules plus conventional treatment is safe and beneficial for adults with gout compared with conventional treatment.

Comparison of mortality and survival without major morbidities of very preterm infants with very low birth weight from Japan and Brazil / Comparação entre mortalidade e sobrevida sem morbidades importantes dos recém-nascidos prematuros de muito baixo peso entre o Japão e o Brasil

Abstract Objective: This study was carried out to understand the disparities in mortality and survival without major morbidities among very premature and very low birth weight infants between participating Neonatal Intensive Care Units (NICUs) from the Brazilian Network on Neonatal Research (RBPN) and the Neonatal Research Network of Japan (NRNJ). Methods: Secondary data analysis of surveys by the RBPN and NRNJ was performed. The surveys were conducted in 2014 and 2015 and included 187 NICUs. Primary outcome was mortality or survival without any major morbidity. Logistic regression analysis adjustment for confounding factors was used. Results: The study population consisted of 6,406 infants from the NRNJ and 2,319 from the RBPN. Controlling for various confounders, infants from RBPN had 9.06 times higher adjusted odds of mortality (95%CI 7.30-11.29), and lower odds of survival without major morbidities (AOR 0.36; 95%CI 0.32-0.41) compared with those from the NRNJ. Factors associated with higher odds of mortality among Brazilian NICUs included: Air Leak Syndrome (AOR 4.73; 95%CI 1.26-15.27), Necrotizing Enterocolitis (AOR 3.25; 95%CI 1.38-7.26), and Late Onset Sepsis (LOS) (AOR 4.86; 95%CI 2.25-10.97). Conclusions: Very premature and very low birth weight infants from Brazil had significantly higher odds for mortality and lower odds for survival without major morbidities in comparison to those from Japan. Additionally, we identified the factors that increased the odds of in-hospital neonatal death in Brazil, most of which was related to LOS.

RESUMO Objetivo: Este estudo foi realizado para compreender as disparidades na mortalidade e sobrevivência sem as principais morbidades entre recém-nascidos muito prematuros e de muito baixo peso entre Unidades de Terapia Intensiva Neonatal (UTINs) participantes da Rede Brasileira de Pesquisas Neonatais (RBPN) e Rede de Pesquisa Neonatal do Japão (NRNJ). Métodos: Foi realizada uma análise dos dados secundários dos bancos de dados da RBPN e da NRNJ. As pesquisas foram realizadas em 2014 e 2015 e incluíram 187 UTINs. O desfecho primário foi mortalidade ou sobrevida sem qualquer morbidade importante. Utilizou-se a análise de regressão logística com ajuste para os fatores de confusão. Resultados: A população do estudo foi composta por 6.406 recém-nascidos do NRNJ e 2.319 do RBPN. Ajustando para diversos fatores de confusão, os prematuros da RBPN tiveram 9,06 vezes maiores chances de mortalidade (IC95% 7,30-11,29) e menores chances de sobrevivência sem morbidades importantes (AOR 0,36; IC95% 0,32-0,41) em comparação com os da NRNJ. Fatores associados a maiores chances de mortalidade entre as UTINs brasileiras incluíram: síndrome de escape de ar (AOR 4,73; IC95% 1,26-15,27), enterocolite necrosante (AOR 3,25; IC95% 1,38-7,26) e sepse de início tardio (AOR 4,86; IC95% 2,25-10,97). Conclusões: Os recém-nascidos muito prematuros e de muito baixo peso do Brasil apresentaram chances significativamente maiores de mortalidade e menores chances de sobrevivência sem as principais morbidades em comparação aos do Japão. Além disso, identificamos os fatores que aumentam as chances da morte neonatal no Brasil, sendo a maioria relacionada à sepse tardia.

Nutrition management by a multidisciplinary team for prevention of nutritional deficits and morbidity following esophagectomy

This study evaluated the effects of perioperative nutrition management by a multidisciplinary team on nutrition and postoperative complications of patients with esophageal cancer. A total of 239 patients with esophageal cancer who underwent esophagectomy and gastric conduit reconstruction for esophageal or esophagogastric junction cancer between February 2019 and February 2020 were included in the study. They were divided into the experimental group (120 patients) and the control group (119 patients) using the random number table method. Control group patients received routine diet management and experimental group patients received perioperative nutrition management by a multidisciplinary team. The differences of nutriture and postoperative complications between the two groups were compared. At 3 and 7 days after surgery, the experimental group patients had higher total protein and albumin levels (P<0.05), shorter postoperative anal exhaust time (P<0.05), lower incidence of postoperative gastrointestinal adverse reactions, pneumonia, anastomotic fistula, hypoproteinemia (P<0.05), and lower hospitalization costs (P<0.05) than the control group. Nutrition management by a multidisciplinary team effectively improved the nutriture of patients, promoted the rapid recovery of postoperative gastrointestinal function, reduced postoperative complications, and reduced hospitalization costs.

Effect of aerobic training on physical fitness and cardiopulmonary resistance of university students / Efeito do treinamento aeróbico sobre a aptidão física e resistência cardiopulmonar dos estudantes universitários / Efecto del entrenamiento aeróbico sobre la aptitud física y la resistencia cardiopulmonar de estudiantes universitarios

ABSTRACT Introduction: The good performance of college students depends directly on their physical integrity, which is subordinated to good physical fitness and cardiopulmonary resistance. It is believed that aerobic training, an adaptation to the progressive increase of physical endurance, may benefit college students. Objective: Study whether aerobic training can affect college students' physical fitness and cardiopulmonary endurance. Methods: Through experimental comparison, the physical fitness and cardiopulmonary endurance of students in the aerobics elective class and the university athletics elective class were compared. Body indexes were measured before and after the intervention, statistically analyzed, and discussed according to the literature. Results: There were significant changes in the 50-meter run time for university students in the elective aerobics class from 9.24±1.71 to 7.81±2.02, the five-meter run from 11.56±1.03 to 7.87±0.23, the standing jump from 156.92±14.79 to 170.56±19.93, and the sitting flexion from 14.07±1.98 to 17.52±3.79. These changes accompanied the changes in cardiorespiratory endurance in the aerobics elective class. In contrast, the changes in student indicators in the track and field elective class were not as evident. Conclusion: Aerobic training positively impacted overall physical quality, including elevation of fitness indices and cardiopulmonary endurance in college students. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: O bom desempenho dos estudantes universitários depende diretamente de sua integridade física, que está subordinada a uma boa aptidão física e resistência cardiopulmonar. Acredita-se que o treinamento aeróbico, uma adaptação ao aumento progressivo da resistência física, possa trazer benefícios aos estudantes universitários. Objetivo: Estudar se a prática do treinamento aeróbico pode afetar a aptidão física e a resistência cardiopulmonar dos estudantes universitários. Métodos: Através de comparação experimental, a aptidão física e a resistência cardiopulmonar dos alunos da classe optativa de aeróbica e da classe optativa de atletismo universitário foram comparadas. Os índices corporais foram mensurados antes e após a intervenção, trabalhados estatisticamente e discutidos conforme a literatura. Resultados: Houveram alterações significativas no tempo de corrida 50 metros pelos estudantes universitários da classe eletiva de aeróbica, de 9,24±1,71 para 7,81±2,02, a de cinco metros foi de 11,56±1,03 para 7,87±0,23, o salto em pé foi de 156,92±14,79 para 170,56±19,93, e a flexão em posição sentada de 14,07±1,98 para 17,52±3,79. Essas alterações acompanharam as mudanças de resistência cardiorrespiratória na classe eletiva de aeróbica, enquanto as mudanças dos indicadores em alunos na classe eletiva de atletismo não foram tão evidentes. Conclusão: O treinamento em aeróbico mostrou um impacto positivo sobre a qualidade física geral, incluindo elevação dos índices de aptidão física e da resistência cardiopulmonar nos estudantes universitários. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: El buen rendimiento de los estudiantes universitarios depende directamente de su integridad física, que está subordinada a una buena forma física y resistencia cardiopulmonar. Se cree que el entrenamiento aeróbico, una adaptación al aumento progresivo de la resistencia física, puede aportar beneficios a los estudiantes universitarios. Objetivo: Estudiar si la práctica del entrenamiento aeróbico puede afectar a la forma física y a la resistencia cardiopulmonar de los estudiantes universitarios. Métodos: Mediante comparación experimental, se compararon la forma física y la resistencia cardiopulmonar de los estudiantes de la clase optativa de aeróbic y de la clase optativa de atletismo universitario. Se midieron los índices corporales antes y después de la intervención, se trabajaron estadísticamente y se discutieron según la bibliografía. Resultados: Hubo cambios significativos en el tiempo de carrera de 50 metros de los estudiantes universitarios de la clase electiva de aeróbic, de 9,24±1,71 a 7,81±2,02, la carrera de cinco metros fue de 11,56±1,03 a 7,87±0,23, el salto de pie fue de 156,92±14,79 a 170,56±19,93, y la flexión en posición sentada de 14,07±1,98 a 17,52±3,79. Estos cambios acompañaron a los cambios de la resistencia cardiorrespiratoria en la clase optativa de aeróbic, mientras que los cambios de los indicadores en los alumnos de la clase optativa de atletismo no fueron tan evidentes. Conclusión: El entrenamiento aeróbico mostró un impacto positivo en la calidad física general, incluyendo la elevación de los índices de condición física y resistencia cardiopulmonar en estudiantes universitarios. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Impacts of pnf stretching on joint flexibility in volleyball athletes / Impactos do alongamento pnf sobre a flexibilidade articular em atletas de vôlei / Impacto de los estiramientos pnf sobre la flexibilidad articular en atletas de voleibol

ABSTRACT Introduction: It is believed that the stretching method by Proprioceptive Neuromuscular Facilitation (PNF) can improve functional joint flexibility through neural stimuli, resulting in more precise movements for volleyball players. Objective: Study the effect of PNF stretching exercise on shoulder joint flexibility in volleyball athletes. Methods: A total of 30 members of a university volleyball team were randomly divided into experimental and control groups. The traditional stretching method was used in the control group, while the PNF stretching method was employed in the experimental group. Data regarding the range of motion and functional quality were collected before and after the intervention for statistical analysis. Results: After eight weeks of the experiment, the left anterior flexion functional score on the shoulder flexibility index of the experimental group increased from 147.05 ± 4.95 to 160.99 ± 4.56; the right frontal flexion score increased from 150.27 ± 5.93 to 162.16 ± 4.46. Shoulder joint stability was gradually stabilized from 88.33 to 101.17. The pass functional score increased from 4.17 ± 1.93 to 18.96 ± 1.77; the overall functional performance score increased from 9.02 ± 4.04 to 23.07 ± 3.96. The control group had an increase without statistical significance. Conclusion: PNF stretching exercises can improve the shoulder joint flexibility of volleyball players. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: Acredita-se que o método de alongamento pela Facilitação Neuromuscular Proprioceptiva (PNF) possa melhorar a flexibilidade funcional articular através de estímulos neurais, resultando em movimentos mais precisos para os jogadores de vôlei. Objetivo: Estudar o efeito do exercício de alongamento PNF sobre a flexibilidade articular no ombro de atletas de voleibol. Métodos: Um total de 30 integrantes de uma equipe universitária de voleibol foram divididos aleatoriamente em grupo experimental e de controle. O método tradicional de alongamento foi usado no grupo controle, enquanto o método de alongamento PNF foi empregado no grupo experimental. Os dados relativos à amplitude de movimento e qualidade funcional foram coletados antes e após a intervenção para análise estatística. Resultados: Após 8 semanas de experimento, a pontuação funcional de flexão anterior esquerda no índice de flexibilidade do ombro do grupo experimental aumentou de 147,05 ± 4,95 para 160,99 ± 4,56; a pontuação de flexão frontal do lado direito aumentou de 150,27 ± 5,93 para 162,16 ± 4,46. A estabilidade da articulação do ombro foi gradualmente estabilizada de 88,33 para 101,17. A pontuação funcional do passe aumentou de 4,17 ± 1,93 para 18,96 ± 1,77; a pontuação do desempenho funcional geral aumentou de 9,02 ± 4,04 para 23,07 ± 3,96. O grupo de controle teve um aumento sem expressividade estatística. Conclusão: O exercício de alongamento PNF pode melhorar a flexibilidade da articulação dos ombros dos jogadores de voleibol. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: Se cree que el método de estiramiento por Facilitación Neuromuscular Propioceptiva (PNF) puede mejorar la flexibilidad funcional articular a través de estímulos neurales, resultando en movimientos más precisos para los jugadores de voleibol. Objetivo: Estudiar el efecto del ejercicio de estiramiento PNF sobre la flexibilidad articular del hombro en atletas de voleibol. Métodos: Un total de 30 miembros de un equipo universitario de voleibol fueron divididos aleatoriamente en grupo experimental y grupo de control. En el grupo de control se utilizó el método de estiramiento tradicional, mientras que en el grupo experimental se empleó el método de estiramiento PNF. Se recogieron datos relativos a la amplitud de movimiento y la calidad funcional antes y después de la intervención para su análisis estadístico. Resultados: Tras 8 semanas de experimento, la puntuación funcional de flexión anterior izquierda en el índice de flexibilidad del hombro del grupo experimental aumentó de 147,05 ± 4,95 a 160,99 ± 4,56; la puntuación de flexión frontal derecha aumentó de 150,27 ± 5,93 a 162,16 ± 4,46. La estabilidad de la articulación del hombro se estabilizó gradualmente de 88,33 a 101,17. La puntuación funcional de paso aumentó de 4,17 ± 1,93 a 18,96 ± 1,77; la puntuación de rendimiento funcional general aumentó de 9,02 ± 4,04 a 23,07 ± 3,96. El grupo de control tuvo un aumento sin expresividad estadística. Conclusión: El ejercicio de estiramiento PNF puede mejorar la flexibilidad de la articulación del hombro de los jugadores de voleibol. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Clinical tolerability and pharmacokinetics of troxacitabine / 中华肿瘤杂志

Objective: To investigate the safety and efficacy of troxatabine in advanced or relapsed malignant tumors resistant to standard therapy in China. Methods: This is a phase Ⅰ prospective study. During dose escalation, patients in Cancer Hospital, Chinese Academy of Medical Sciences received a single-dose intravenous infusion of troxacitabine. The planned dosing groups were 1.8, 3.6, 4.8, 6.4 and 8.0 mg/m(2) on days 1 and 8 every 3 weeks. The data of all patients were collected for safety analyses. Safety and tolerability were evaluated by monitoring adverse events. Results: Nineteen patients were enrolled from April 2018 to May 2019. The major adverse events were fatigue (89.5%, 17/19), leukopenia (84.2%, 16/19) and neutropenia (78.9%, 15/19). The dose limiting toxicity was neutropenia. The maximum tolerated dose was 6.4 mg/m(2). The best effect was stable disease (43.8%). The half-life of elimination phase from 15.91 hours to 76.63 hours in each dose group. Conclusions: The toxicity of troxacitabine is well tolerant. We recommend that the dose for Phase Ⅱ clinical trial should be 6.4 mg/m(2).

Efficacy and safefy of Polymyxin B treatment for neutropenic patients suffering from refractory Gram-negative bacterial bloodstream infection / 中华血液学杂志

Objective: To assess the efficacy and safety of polymyxin B in neutropenic patients with hematologic disorders who had refractory gram-negative bacterial bloodstream infection. Methods: From August 2021 to July 2022, we retrospectively analyzed neutropenic patients with refractory gram-negative bacterial bloodstream infection who were treated with polymyxin B in the Department of Hematology of the First Affiliated Hospital of the Soochow University between August 2021 to July 2022. The cumulative response rate was then computed. Results: The study included 27 neutropenic patients with refractory gram-negative bacterial bloodstream infections. Polymyxin B therapy was effective in 22 of 27 patients. The median time between the onset of fever and the delivery of polymyxin B was 3 days [interquartile range (IQR) : 2-5]. The median duration of polymyxin B treatment was 7 days (IQR: 5-11). Polymyxin B therapy had a median antipyretic time of 37 h (IQR: 32-70). The incidence of acute renal dysfunction was 14.8% (four out of 27 cases), all classified as "injury" according to RIFLE criteria. The incidence of hyperpigmentation was 59.3%. Conclusion: Polymyxin B is a viable treatment option for granulocytopenia patients with refractory gram-negative bacterial bloodstream infections.

Effect and safety of 10-day decitabine-containing conditioning regimen for allogeneic hematopoietic stem cell transplantation in 31 patients with acute myeloid leukemia/myelodysplastic syndrome / 中华血液学杂志

Objective: To investigate the early effect and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with a 10-day decitabine-containing conditioning regimen in the treatment of acute myeloid leukemia (AML) /myelodysplastic syndrome (MDS) . Methods: From April 2021 to May 2022, 31 AML/MDS patients who received allo-HSCT with a 10-day decitabine-containing conditioning regimen were analyzed. Results: AML (n=10), MDS-AML (n=6), CMML-AML (n=1), and MDS (n=14) were identified in 31 patients, 16 males, and 15 females, with a median age of 41 (20-55) yr. Neutrophils and platelets were successfully implanted in 31 patients (100%), with a median implantation duration of 12 (9-30) and 14 (9-42) days, respectively. During the preconditioning period, 16 patients (51.6%) developed oral mucositis, with 15 cases of Ⅰ/Ⅱ grade (48.4%) and one case of Ⅲ grade (3.2%). After transplantation, 13 patients (41.9%) developed CMV viremia, six patients (19.4%) developed hemorrhagic cystitis, and four patients (12.9%) developed a local infection. The median time of acute graft versus host disease (aGVHD) following transplantation was 33 (12-111) days. The cumulative incidence of aGVHD and Ⅲ/Ⅳ grade aGVHD was 41.9% (95% CI 26.9%-61.0%) and 22.9% (95% CI 13.5%-47.5%), respectively. There was no severe cGVHD, and mild and moderate chronic GVHD (cGVHD) incidence was 23.5% (95% CI 12.1%-43.6%). As of November 30, 2022, only one of the 31 patients had relapsed, with a 1-yr cumulative relapse rate (CIR) of 3.2% (95% CI 0.5%-20.7%). There was only one relapse patient death and no non-relapse deaths. The 1-yr overall survival (OS) and disease-free survival (DFS) rates were 92.9% (95% CI 80.3%-100%) and 96.8% (95% CI 90.8%-100%), respectively. Conclusions: A 10-day decitabine-containing conditioning regimen for allo-HSCT reduced relapse and was safe and feasible in treating AML/MDS.

A single-centre experience of His bundle pacing without electrophysiological mapping system: implant success rate, safety, pacing characteristics and one-year follow up

INTRODUCTION@#Despite the challenges related to His bundle pacing (HBP), recent data suggest an improved success rate with experience. As a non-university, non-electrophysiology specialised centre in Singapore, we report our experiences in HBP using pacing system analyser alone.@*METHODS@#Data of 28 consecutive patients who underwent HBP from August 2018 to February 2019 was retrospectively obtained. The clinical and technical outcomes of these patients were compared between two timeframes of three months each. Patients were followed up for 12 months.@*RESULTS@#Immediate technical success was achieved in 21 (75.0%) patients (mean age 73.3 ± 10.7 years, 47.6% female). The mean left ventricular ejection fraction was 53.9% ± 12.1%. The indications for HBP were atrioventricular block (n = 13, 61.9%), sinus node dysfunction (n = 7, 33.3%) and upgrade from implantable cardioverter-defibrillator to His-cardiac resynchronisation therapy (n = 1, 4.8%). No significant difference was observed in baseline characteristics between Timeframe 1 and Timeframe 2. Improvements pertaining to mean fluoroscopy time were achieved between the two timeframes. There was one HBP-related complication of lead displacement during Timeframe 1. All patients with successful HBP achieved non-selective His bundle (NSHB) capture, whereas only eight patients had selective His bundle (SHB) capture. NSHB and SHB capture thresholds remained stable at the 12-month follow-up.@*CONCLUSION@#Permanent HBP is feasible and safe, even without the use of an electrophysiology recording system. This was successfully achieved in 75% of patients, with no adverse clinical outcomes during the follow-up period.

Quantitative analysis of myocardial fibrosis in dilated cardiomyopathy with deep learning joint segmentation model / 中华放射学杂志

Objective:To explore the effect of joint segmentation model of myocardial-fibrotic region based on deep learning in quantitative analysis of myocardial fibrosis in patients with dilated cardiomyopathy(DCM).Methods:The data of 200 patients with confirmed DCM and myocardial fibrosis in the left ventricle detected by cardiac MR-late gadolinium enhancement (CMR-LGE) in Xuzhou Central Hospital from January 2015 to April 2022 were retrospectively analyzed. Using a complete randomized design, the patients were divided into training set ( n=120), validation set ( n=30) and test set ( n=50). The left ventricle myocardium was outlined and the normal myocardial region was selected by radiologists. Fibrotic myocardium was extracted through calculating the threshold with standard deviation (SD) as a reference standard for left ventricle segmentation and fibrosis quantification. The left ventricular myocardium was segmented by convex prior U-Net network. Then the normal myocardial image block was recognized by VGG image classification network, and the fibrosis myocardium was extracted by SD threshold. The myocardial segmentation effect was evaluated using precision, recall, intersection over union (IOU) and Dice coefficient. The consistency of myocardial fibrosis ratio in left ventricle obtained by joint segmentation model and manual extraction was evaluated with intra-class correlation coefficient (ICC). According to the median of fibrosis rate, the samples were divided into mild and severe fibrosis, and the quantitative effect of fibrosis was compared by Mann-Whitney U test. Results:In the test set, the precision of myocardial segmentation was 0.827 (0.799, 0.854), the recall was 0.849 (0.822, 0.876), the IOU was 0.788 (0.760, 0.816), and the Dice coefficient was 0.832 (0.807, 0.857). The consistency of fibrosis ratio between joint segmentation model and manual extraction was high (ICC=0.991, P<0.001). No statistically significant difference was found in the ratio error between mild and severe fibrosis ( P>0.05). Conclusions:The joint segmentation model realizes the automatic calculation of myocardial fibrosis ratio in left ventricle, which is highly consistent with the results of manual extraction. Therefore, it can accurately realize the automatic quantitative analysis of myocardial fibrosis in patients with dilated cardiomyopathy.

Risk factor assessment and adverse outcome prediction of placenta accreta in pregnant women after cesarean section complicated with placenta previa: a national multicenter retrospective study / 中华妇产科杂志

Objective:To study the risk factors of adverse pregnancy outcomes for the diagnosis and treatment of pregnancy after cesarean section complicated with placenta previa.Methods:A national multicenter retrospective study was conducted to select a total of 747 pregnant women with the third trimester singleton pregnancy after cesarean section complicated with placenta previa from 12 tertiary hospitals in January 1st to December 31st, 2018. The risk factors of severe adverse outcomes [hysterectomy, intraoperative blood loss ≥1 000 ml, intraoperative diagnosis of placenta accreta spectrum disorders (PAS)] in pregnant women with second pregnancy complicated with placenta previa after cesarean section were investigated by logistic regression analysis. The roles of prenatal ultrasonography and magnetic resonance imaging (MRI) in the prediction of PAS and severe adverse outcomes were observed. According to whether vascular intervention was performed (uterine artery embolization or abdominal aortic balloon occlusion), the pregnant women were divided into the blocked group and the unblocked group, and the maternal and infant perinatal outcomes between the two groups were compared.Results:(1) General information: the hysterectomy rate of 747 pregnant women with second pregnancy complicated with placenta previa after cesarean section was 10.4% (78/747), the intraoperative blood loss ≥1 000 ml in 55.8% (417/747), and PAS was confirmed in 47.5% (355/747). The incidence of uterine rupture was 0.8% (6/747). (2) Analysis of risk factors for severe adverse outcomes: based on binary unconditioned logistic regression univariate and multivariate analysis, the risk factors for hysterectomy were the mode of vascular embolization and intraoperative blood loss. The probability of hysterectomy with uterine artery embolization was 5.319 times higher than that with abdominal aortic balloon occlusion (95% CI: 1.346-21.018). The risk factors of intraoperative blood loss ≥1 000 ml were the number of cesarean section delivery, ultrasonography indicated PAS and suspected PAS, intraoperative PAS and complete placenta previa. The risk factors for intraoperative PAS were uterine scar thickness, ultrasonography indicated PAS and suspected PAS, MRI indicated PAS and suspected PAS, and complete placenta previa. (3) The roles of ultrasonography and MRI in predicting PAS: the sensitivity and specificity of ultrasonography in predicting PAS were 47.5% and 88.4%; the kappa value was 0.279 ( P<0.001), with fair agreement. The sensitivity and specificity of MRI to predict PAS were 79.2% and 97.8%, respectively. The kappa value was 0.702 ( P<0.001), indicating a good agreement. The intraoperative blood loss and hysterectomy rate of pregnant women with PAS indicated by ultrasonography and MRI were significantly higher than those with PAS only by ultrasonography or MRI. (4) Influence of vascular occlusion on pregnancy outcome: there were no significant differences in intraoperative blood loss and incidence of intraoperative bleeding ≥1 000 ml between the blocked group and the unblocked group (all P>0.05). There was no significant difference in intraoperative blood loss between the pregnant women with abdominal aortic balloon occlusion, uterine artery embolization and those without occlusion ( P=0.409). The hysterectomy rate of pregnant women with uterine artery embolization was significantly higher than those with abdominal aortic balloon occlusion [39.3% (22/56) vs 10.0% (5/50), P=0.001]. Conclusions:In the third trimester of pregnancy with placenta previa after cesarean section, MRI examination has better consistency in predicting PAS than ultrasonography examination. Ultrasonography examination combined with MRI examination could effectively predict the hysterectomy rate and intraoperative blood loss. Vascular occlusion could not reduce the amount of intraoperative blood loss. The hysterectomy rate of pregnant women with uterine artery embolization is higher than those with abdominal aortic balloon occlusion.

The impact of portal vein thrombosis on the long-term efficacy of endoscopic treatment for acute esophageal and gastric variceal bleeding patients / 中国医师杂志

Objective:To evaluate the long-term risk of rebleeding in patients with acute esophageal and gastric variceal bleeding and portal vein thrombosis after endoscopic treatment in liver cirrhosis.Methods:From January to December 2022, 57 patients with acute esophageal and gastric variceal bleeding who were treated by endoscopy in the emergency department of the Zhongshan Hospital affiliated to the Fudan University were included in the study. According to the results of portal vein CT angiography (CTA), the patients were divided into thrombosis group and non thrombosis group. We compared the basic information and endoscopic treatment status of two groups of patients. All patients were followed up until 1 year after endoscopic treatment or April 15, 2023, and re bleeding and survival were recorded during the follow-up period. The influencing factors of rebleeding after 1 year of treatment were analyzed.Results:The patient′s age was (55.9±11.4)years old, mainly male [78.95%(45/57)]. The average time from initial bleeding to endoscopic treatment for all patients was (6.6±2.8)days. There was no statistically significant difference between the two groups in terms of age, sex, combined liver malignancy, Child-pugh score, first bleeding form, ascites, and first laboratory examination results (including hemoglobin, platelet, Prothrombin time, creatinine) (all P>0.05). There was no statistically significant difference in the history of endoscopic treatment, bleeding distance from endoscopic treatment, the proportion of patients with esophageal varices and gastric varices, the proportion of patients with esophageal varices treated with ligation, and the proportion of patients with gastric varices treated with tissue glue between the two groups (all P>0.05). A total of 2 patients died after surgery, and 12 patients experienced rebleeding, including 10 in the thrombotic group and 2 in the non thrombotic group. Kaplan Meier analysis showed that the 1-year rebleeding rate in the thrombotic group was significantly higher than that in the non thrombotic group (59.02% vs 24.71%, RR=6.002, 95% CI: 1.06-34.00, P=0.020 8). Cox multivariate regression analysis suggests that the presence of portal vein thrombosis ( HR=7.669, 95% CI: 1.453-40.472, P=0.016) was an independent risk factor for recurrent bleeding after endoscopic treatment of acute esophageal and gastric variceal bleeding for one year. Conclusions:Portal vein thrombosis in liver cirrhosis increases the risk of recurrent bleeding after endoscopic treatment for acute esophageal and gastric variceal bleeding for one year. For patients with acute Upper gastrointestinal bleeding complicated with portal vein thrombosis, regular endoscopic and ultrasonic follow-up, individualized endoscopic sequential and selective anticoagulation therapy should be carried out.

Triaging patients in the outbreak of COVID-2019 / 中国感染控制杂志

In the outbreak of COVID-19,triage procedures based on epidemiology were implemented in a local hospital in Changsha to control the transmission of SARS-CoV-2 and avoid healthcare-associated infection.This re-trospective study analyzed the data collected during the triage period and found that COVID-19 patients were en-riched 7 folds into the Section A designated for patients with obvious epidemiological history.On the other side,nearly triple amounts of visits were received at the Section B for patients without obvious epidemiological history.8 COVID-19 cases were spotted out of 247 suspected patients.More than 50％of the suspected patients were submi-tted to multiple rounds of nucleic acid analysis for SARS-CoV-2 infection.Of the 239 patients who were diagnosed as negative of the virus infection,188 were successfully revisited and none was reported as COVID-19 case.Of the 8 COVID-19 patients,3 were confirmed only after multiple rounds of nucleic acid analysis.Besides comorbidities,delayed sharing of epidemiological history added complexity to the diagnosis in practice.The triaging experience and strategy will be helpful for the control of infectious diseases in the future.

Benzodiazepines in complex biological matrices:Recent updates on pretreatment and detection methods / 药物分析学报

Benzodiazepines(BDZs)are used in clinics for anxiolysis,anticonvulsants,sedative hypnosis,and muscle relaxation.They have high consumptions worldwide because of their easy availability and potential addiction.They are often used for suicide or criminal practices such as abduction and drug-facilitated sexual assault.The pharmacological effects of using small doses of BDZs and their detections from complex biological matrices are challenging.Efficient pretreatment methods followed by accurate and sensitive detections are necessary.Herein,pretreatment methods for the extraction,enrichment,and preconcentration of BDZs as well as the strategies for their screening,identification,and quantitation developed in the past five years have been reviewed.Moreover,recent advances in various methods are summarized.Characteristics and advantages of each method are encompassed.Future directions of the pretreatment and detection methods for BDZs are also reviewed.

Epigenetic drug library screening reveals targeting DOT1L abrogates NAD+synthesis by reprogramming H3K79 methylation in uveal melanoma / 药物分析学报

Uveal melanoma(UM)is the most frequent and life-threatening ocular malignancy in adults.Aberrant histone methylation contributes to the abnormal transcriptome during oncogenesis.However,a comprehensive understanding of histone methylation patterns and their therapeutic potential in UM remains enigmatic.Herein,using a systematic epi-drug screening and a high-throughput transcriptome profiling of histone methylation modifiers,we observed that disruptor of telomeric silencing-1-like(DOT1L),a methyltransferase of histone H3 lysine 79(H3K79),was activated in UM,especially in the high-risk group.Concordantly,a systematic epi-drug library screening revealed that DOT1 L inhibitors exhibited salient tumor-selective inhibitory effects on UM cells,both in vitro and in vivo.Combining Cleavage Under Targets and Tagmentation(CUT&Tag),RNA sequencing(RNA-seq),and bioinformatics analysis,we identified that DOT1 L facilitated H3K79 methylation of nicotinate phosphoribosyltransferase(NAPRT)and epigenetically activated its expression.Importantly,NAPRT served as an oncogenic accel-erator by enhancing nicotinamide adenine dinucleotide(NAD+)synthesis.Therapeutically,DOT1L inhi-bition epigenetically silenced NAPRT expression through the diminishment of dimethylation of H3K79(H3K79me2)in the NAPRT promoter,thereby inhibiting the malignant behaviors of UM.Conclusively,our findings delineated an integrated picture of the histone methylation landscape in UM and unveiled a novel DOT1L/NAPRT oncogenic mechanism that bridges transcriptional addiction and metabolic reprogramming.