Development and evaluation of Tamil Matrix Sentence Test Performance in young adults

ABSTRACT Purpose The purpose of the study was to develop the Tamil Matrix Sentence Test (TMST) and evaluate the performance of a group of young adults with normal hearing on the developed test. The developed sentences were also administered at varying intensities to obtain a performance-intensity (PI) function. Methods A base matrix with 10 sentences containing 5 words each with a total of 50 words was used to develop the TMST. The sentences had a fixed semantic sentence structure of Tamil language in the order of noun, number, adjective, object and verb. The developed test consisted of 30 lists with 10 sentences in each list. The performance of 60 young adults with normal hearing aged 18 to 24 years across the 30 lists were compared for list equivalency. To obtain the PI function the sentences were administered on 20 young adults with normal hearing at intensities from 20 dB HL to 100 dB HL in 10 dB increments. The performance across the intensity levels were compared. Results The 30 lists of TMST were found to be acoustically equivalent. However, few lists showed significant difference in the scores obtained on them compared to the rest of the lists. The PI function revealed a saturation in performance beyond 40 dB HL. Conclusion From the results it was construed that TMST can be used to evaluate the speech identification abilities of Tamil speaking listeners. Multiple lists offer the advantage of retesting without the influence of practice or listeners memorizing the test material.

Acute physiological responses to "recovery intermittent hypoxia" in hiit / Respuestas agudas a la "hipoxia intermitente de recuperación" en el hiit / Respostas fisiológicas agudas à "hipóxia intermitente de recuperação" no hiit

ABSTRACT Introduction: Traditional intermittent hypoxia training improves sport performance after short periods of exposure, but acute exposure to intermittent hypoxia leads to decreased training intensity and technical quality. The solution to overcome these negative effects may be to perform efforts in normoxia and the intervals between efforts in hypoxia, maintaining the quality of training and the benefits of hypoxia. Objective: This study aimed to evaluate the acute physiological responses to hypoxia exposure during recovery between high intensity efforts. Materials and methods: Randomized, one-blind, placebo-controlled study. Sixteen men performed a graded exercise test to determine their maximal intensity and two sessions of high-intensity interval training. The training intervals could be in hypoxia (HRT), FIO2: 0.136 or normoxia (NRT), FIO2: 0.209. During the two-minute interval between the ten one-minute efforts, peripheral oxygen saturation (SpO2), heart rate (HR), blood lactate ([La]), blood glucose ([Glu]) were constantly measured. Results: There were differences in HR (TRN = 120 ± 14 bpm; TRH = 129 ± 13 bpm, p < 0.01) and SpO2 (TRN = 96.9 ± 1.0%; TRH = 86.2 ± 3.5%, p < 0.01). No differences in [La] and [Glu] TRN (4.4 ± 1.7 mmol.l-1; 3.9 ± 0.5 mmol.l-1) and TRH (5.2 ± 2.0 mmol.l-1; 4.0 ± 0.8 mmol.l-1, p = 0.17). Conclusion: The possibility of including hypoxia only in the recovery intervals as an additional stimulus to the training, without decreasing the quality of the training, was evidenced. Level of Evidence II; Randomized Clinical Trial of Minor Quality.

RESUMEN Introducción: El entrenamiento tradicional en hipoxia intermitente mejora el rendimiento deportivo tras cortos periodos de exposición, sin embargo, la exposición aguda a la hipoxia intermitente conduce a una disminución de la intensidad del entrenamiento y de la calidad técnica. La solución para superar estos efectos negativos puede ser realizar los esfuerzos en normoxia y los intervalos entre esfuerzos en hipoxia, manteniendo la calidad del entrenamiento y los beneficios de la hipoxia. Objetivo: Este estudio pretendía evaluar las respuestas fisiológicas agudas a la exposición a la hipoxia durante la recuperación entre esfuerzos de alta intensidad. Materiales y métodos: Estudio aleatorizado, a ciegas y controlado con placebo. Dieciséis hombres realizaron una prueba de ejercicio graduado para determinar su intensidad máxima y dos sesiones de entrenamiento por intervalos de alta intensidad. Los intervalos de entrenamiento podían ser en hipoxia (HRT), FIO2: 0,136 o normoxia (NRT), FIO2: 0,209. Durante el intervalo de dos minutos entre los diez esfuerzos de un minuto, se midieron constantemente la saturación periférica de oxígeno (SpO2), la frecuencia cardiaca (FC), el lactato en sangre ([La]) y la glucemia ([Glu]). Resultados: Hubo diferencias en la FC (TRN = 120 ± 14 lpm; TRH = 129 ± 13 lpm, p < 0,01) y la SpO2 (TRN = 96,9 ± 1,0%; TRH = 86,2 ± 3,5%, p < 0,01). No hubo diferencias en [La] y [Glu] TRN (4,4 ± 1,7 mmol.l-1; 3,9 ± 0,5 mmol.l-1) y TRH (5,2 ± 2,0 mmol.l-1; 4,0 ± 0,8 mmol.l-1, p = 0,17). Conclusión: Se evidenció la posibilidad de incluir hipoxia sólo en los intervalos de recuperación como estímulo adicional al entrenamiento sin disminuir la calidad del mismo. Nivel de Evidencia II; Ensayo Clínico Aleatorizado de Baja Calidad.

RESUMO Introdução: O treinamento de hipóxia intermitente tradicional melhora o desempenho esportivo após curtos períodos de exposição, porém a exposição aguda à hipóxia intermitente leva à diminuição da intensidade do treinamento e da qualidade técnica. A solução para superar esses efeitos negativos pode ser realizar esforços em normóxia e os intervalos entre os esforços em hipóxia, mantendo a qualidade do treinamento e os benefícios da hipóxia. Objetivo: Este estudo teve como objetivo avaliar as respostas fisiológicas agudas à exposição de hipóxia durante a recuperação entre esforços de alta intensidade. Materiais e métodos: Estudo aleatório e one-blinded, com efeito placebo controlado. Dezesseis homens realizaram um teste de exercício graduado para determinar sua intensidade máxima e duas sessões de treinamento intervalado de alta intensidade. Os intervalos de treinamento podem ser em hipóxia (TRH), FIO2: 0,136 ou normóxia (TRN), FIO2: 0,209. Durante os dois minutos de intervalo entre os dez esforços de um minuto, foram medidos constantemente a saturação periférica de oxigênio (SpO2), frequência cardíaca (FC), lactato sanguíneo ([La]), glicemia ([Glu]). Resultados: Houve diferenças na FC (TRN = 120 ± 14 bpm; TRH = 129 ± 13 bpm, p <0,01) e SpO2 (TRN = 96,9 ± 1,0%; TRH = 86,2 ± 3,5%, p <0,01). Sem diferenças em [La] e [Glu] TRN (4,4 ± 1,7 mmol.l-1; 3,9 ± 0,5 mmol.l-1) e TRH (5,2 ± 2,0 mmol.l-1; 4,0 ± 0,8 mmol.l-1, p = 0,17). Conclusão: Evidenciou-se a possibilidade de incluir a hipóxia apenas nos intervalos de recuperação como um estímulo adicional ao treinamento, sem diminuir a qualidade do treinamento. Nível de Evidência II; Estudo Clínico Randomizado de Menor Qualidade.

High-intensity interval training in people with spinal cord injury: a systematic review / Entrenamiento por intervalos de alta intensidad en personas con lesiones medulares: una revisión sistemática / Treinamento intervalado de alta intensidade em pessoas com lesão da medula espinhal: revisão sistemática

ABSTRACT Objective: Analyze the effects of high-intensity interval training (HIIT) on cardiometabolic parameters, and cardiorespiratory fitness to compile the most used HIIT training types in adults with spinal cord injury (SCI). Methods: This is a systematic review of searches performed in the electronic databases PubMed / Medline, Science Direct, and Google Scholar. Studies included I) needed to apply HIIT training II) adults with SCI to analyze III) cardiometabolic aspects and cardiorespiratory fitness. Two independent reviewers selected the articles for inclusion, extracted their data, and assessed their methodological quality. Results: 654 studies were found. Thus, 12 studies, 11 pre- and post-intervention, and one control group (CG) with 106 participants were analyzed. Pre- and post-HIITT intervention results revealed significant improvement in cardiorespiratory fitness and cardiometabolic aspects (VO2peak, LDH, HDL, insulin resistance). In addition, GC results revealed significant improvement in cardiorespiratory fitness observed in the intervention group (HIIT) compared to the moderate-low intensity (GC) group. Seven studies used the arm ergometer as the primary exercise modality. Two studies described functional electrical stimulation (FES) performed with the arm ergometer plus electrical stimulation in the lower limbs. None reported heart rate dynamics during the study period. Conclusion: High-intensity interval training improves physical fitness and cardiometabolic health in adults with SCI. Evidence level II; Systematic Review of level II studies.

RESUMEN Objetivo: Analizar los efectos del entrenamiento interválico de alta intensidad (HIIT) sobre los parámetros cardiometabólicos, fitness cardiorrespiratorio y recopilar los tipos de HIIT más utilizados en el entrenamiento en adultos con lesión medular (LME). Métodos: Se trata de una revisión sistemática, para lo cual se realizaron búsquedas en bases de datos electrónicas PubMed/Medline, Science Direct y Google Scholar. Se incluyeron estudios que I) necesitaban aplicar entrenamiento HIIT en II) adultos con SCI y analizar III) aspectos cardiometabólicos y aptitud cardiorrespiratoria. Dos revisores independientes seleccionaron los artículos para su inclusión, extrajeron sus datos y evaluaron su calidad metodológica. Resultados: De los 654 estudios encontrados, se analizaron 12 estudios, 11 pre y post intervención y 1 grupo control (GC) con un total de 106 participantes. Los resultados previos y posteriores a la intervención HIIT revelaron una mejora significativa en la aptitud cardiorrespiratoria y los aspectos cardiometabólicos (VO2pico, LDH, HDL, resistencia a la insulina). Los resultados de GC revelaron una mejora significativa en la aptitud cardiorrespiratoria observada del grupo de intervención (HIIT) en comparación con el grupo de intensidad moderada-baja (GC). Siete estudios utilizaron el ergómetro de brazo como la modalidad principal de ejercicio. Dos estudios describieron la estimulación eléctrica funcional (EEF) realizada con el ergómetro de brazo más la estimulación eléctrica en los miembros inferiores. Ninguno informó la dinámica de la frecuencia cardíaca durante el período de estudio. Conclusiones: El entrenamiento intervalos de alta intensidad mejora la condición física y la salud cardiometabólica en adultos con LME. Evidencia de nivel II; Revisión sistemática de estudios de nivel II.

RESUMO Objetivo: Analisar os efeitos do treinamento intervalado de alta intensidade (HIIT) nos parâmetros cardiometabólicos, aptidão cardiorrespiratória e compilar os tipos de HIIT mais utilizados no treinamento em adultos com lesão da medula espinhal (LME). Métodos: Trata-se de revisão sistemática, para a qual foram realizadas pesquisas nas bases de dados eletrônicas PubMed / Medline, Science Direct e Google Scholar. Foram incluídos estudos em que I) o treinamento HIIT era aplicado em II) adultos com LME e analisaram III) os aspectos cardiometabólicos e aptidão cardiorrespiratória. Dois revisores independentes selecionaram os artigos para a inclusão, extraindo seus dados e avaliarando a sua qualidade metodológica. Resultados: 654 estudos foram encontrados. Desses, 12 estudos, 11 pré e pós intervenção e 1 grupo controle (GC) com um total de 106 participantes foram analisados. Resultados pré e pós intervenção de HIIT revelaram significante melhora na aptidão cardiorrespiratória e aspectos cardiometabólicos (VO2pico, LDH, HDL, resistência à insulina). Resultados do GC revelaram uma significativa melhoria na aptidão cardiorrespiratória observada no grupo de intervenção (HIIT) em relação ao grupo de intensidade moderada-baixa (GC). Sete estudos usaram o ergômetro de braço como modalidade de exercício primária. Dois estudos descreveram a estimulação elétrica funcional (EEF) realizada com o ergômetro de braço adicionando estimulação elétrica nos membros inferiores. Nenhum relatou a dinâmica da frequência cardíaca durante o período do estudo. Conclusão: O treinamento intervalado de alta intensidade melhora a aptidão física e a saúde cardiometabólica em adultos com LME. Nível de evidência II; Revisão sistemática de Estudos de Nível II.

Application of vascular photobiomodulation therapy in individuals with low back pain and its relationship with global methylation / Aplicação da terapia por fotobiomodulação vascular em indivíduos com lombalgia e sua relação com a metilação global

ABSTRACT BACKGROUND AND OBJECTIVES: Low back pain is among the most disabling conditions worldwide, and among the epigenetic factors, methylation in CpG islands of gene promoter regions can modulate gene expression, potentially correlating with the development of the disease and providing insights into the choice of treatment. The objective of this study was to assess the efficacy of therapy using modified ILIB related to DNA methylation processes in low back pain. Secondary objectives of this study included investigating pain intensity, gender, sociodemographic data, and physical-functional profile. METHODS: This prospective study was conducted in a municipality in the southern region of Brazil. The sample consisted of 30 participants of both genders, with an average age of 41.77 years. The following aspects were analyzed: anthropometric characteristics, global methylation using the ELISA method, pain level, physical activity level, functional disabilities, and hesitancy level related to work and physical activity-related activities. RESULTS: A statistically significant association was observed between methylation levels before and after treatment application for the experimental and placebo groups (p < 0.005), demonstrating a mean responsiveness between methylation and treatment (d = 0.5). However, there were no other statistically significant associations correlated with the other work variables. CONCLUSION: The results obtained in this study suggest the need for further research related to the identification of specific genes in methylation, as well as the standardization of dosimetry used for transcutaneous ILIB laser application in the radial artery.

RESUMO JUSTIFICATIVA E OBJETIVOS: A lombalgia está entre as condições mais incapacitantes no mundo e; dentre os fatores epigenéticos, a metilação em ilhas CpG de regiões promotoras de genes pode modular a expressão gênica permitindo uma possível correlação ao desenvolvimento da doença, como também pode trazer esclarecimentos a respeito do tratamento a ser escolhido. O objetivo deste estudo foi verificar a eficácia da terapia através do uso do ILIB modificado relacionada ao processo de metilação de DNA na lombalgia. Os objetivos secundários deste estudo foram a investigação da intensidade da dor, sexo, dados sociodemográficos e perfil físico-funcional. MÉTODOS: Este estudo, desenvolvido em um município da região sul do Brasil, caracteriza-se como prospectivo. A amostra deste estudo foi composta por 30 participantes, de ambos os sexos, com idade média de 41,77 anos. Foram analisados os seguintes aspectos: características antropométricas, metilação global através do método ELISA, nível de dor, nível de atividade física, incapacidades funcionais e nível de hesitação para realizar atividades relacionada ao trabalho e atividade física. RESULTADOS: Observou-se associação estatisticamente significativa entre os níveis de metilação antes e a após aplicação do tratamento para grupo experimental e placebo (p<0,005) demostrando uma média responsividade entre as variáveis metilação e tratamento (d=0,5). No entanto, não houve nenhuma outra associação estatística correlacionada as demais variáreis do trabalho. CONCLUSÃO: Os resultados obtidos neste estudo sugerem que há necessidade mais estudos relacionados a identificação de genes específicos na metilação, além da necessidade de padronização de dosimetria utilizadas para aplicação do laser ILIB de forma transcutânea, em artéria radial.

Dosimetric comparison of three?dimensional conformal radiation therapy, intensity?modulated radiation therapy, and volumetric?modulated arc therapy for free?breathing whole?breast irradiation: A planning study

Background: Currently, recommended heart dose constraints are difficult to meet in whole?breast irradiation (WBI) for left?sided breast cancer patients, who cannot be treated with the deep inspiration breath hold. We performed a radiotherapy planning study to establish if the use of intensity?modulated radiation therapy (IMRT) or volumetric?modulated arc therapy (VMAT) allows for better sparing of the heart and its subvolumes than the three?dimensional conformal radiation therapy (3D?CRT), and how these attempts affect the dose delivered to the other organs. Methods: A total of 17 left?sided and 10 right?sided consecutive patients treated with free?breathing WBI were retrospectively included. The 3D?CRT, IMRT, and VMAT plans were generated. Several dose杤olume parameters and plan quality indices were compared, separately for the left? and right?sided plans. Results: All the techniques fulfilled the planning objectives. In the left?sided plans, there was no heart or left ventricle dose reduction with IMRT, nor with VMAT; the maximum dose in the left anterior descending coronary artery was reduced with VMAT (P = 0.005); V5 for the contralateral breast, contralateral lung, and total?body increased markedly in VMAT, and for the ipsilateral lung (V5IL) also in IMRT, compared with 3D?CRT (P < 0.001). In the right?sided plans, the V5 values, except for V5IL, did not differ between the three techniques. Conclusions: IMRT and VMAT had a limited heart?sparing benefit in the left?sided free?breathing WBI, at the cost of increased low?dose volumes, measured by V5. The low?dose volumes are not increased by IMRT or VMAT in the right?sided WBI, where heart sparing is not a problem, but the attempts to reduce cardiac doses in the left?sided WBI increase them.

High-intensity laser for the treatment of pain: systematic review / Laser de alta intensidade para tratamento da dor: revisão sistemática

ABSTRACT BACKGROUND AND OBJECTIVES: Pain is one of the most prevalent causes of disability in the world, and the adverse effects promoted by analgesics can limit therapeutic success. In this context, laser appears as a complementary therapy that can enhance analgesia without increasing the incidence of undesirable adverse events. The aim of this study was to carry out a systematic review on the effectiveness and efficiency of high intensity laser (HIL) in the treatment of pain. CONTENTS: A systematic search was carried out in Medline, LILACS, Pubmed and PEDro, from July 2020 to August 2022. The keywords pain, chronic pain, high intensity laser and treatment were considered. The quality of selected studies was assessed using the PEDro scale. Included systematic reviews were assessed for methodological quality using the AMSTAR tool. The main measure studied was pain intensity. 227 studies were found and, based on the inclusion and exclusion criteria, 32 articles were read in full, whit one being excluded for not assessing pain. Musculoskeletal disorders corresponded to 70,96% of the assessed diseases and the visual analogue scale (VAS) was the only pain measurement tool used in 100% of the studies. Approximately 57% of the studies were of high methodological quality (PEDro=7). In 53,84% of the trials, HIL was used as a single intervention, and in 46,16% it was associated whit exercises. In 96.15% of clinical trials and 100% of systematic reviews there were positive effects of HIL on pain. CONCLUSION: HIL is an effective modality for analgesia by promoting significant pain relief, rapid recovery and improvement in patient's quality of life, in a safe way. The diversity in irradiation parameters (dose, duration, interval and number of sessions) used, indicates the need for further randomized studies to establish its long-term efficiency.

RESUMO JUSTIFICATIVA E OBJETIVOS: A dor é uma das causas mais prevalentes de incapacidade no mundo, e os efeitos adversos promovidos pelos analgésicos podem limitar o sucesso terapêutico. Nesse contexto, surge o laser como terapia complementar que pode potencializar a analgesia, sem aumentar incidência de eventos adversos indesejáveis. O objetivo deste estudo foi realizar uma revisão sistemática sobre a eficácia e a eficiência do laser de alta intensidade (LAI) no tratamento da dor. CONTEÚDO: Foi realizada uma busca sistemática nas plataformas Medline, LILACS, Pubmed e PEDro, de julho de 2020 a agosto de 2022. As palavras chaves dor, dor crônica, laser de alta intensidade e tratamento foram consideradas. A qualidade dos estudos clínicos selecionados foi avaliada utilizando a escala PEDro. As revisões sistemáticas incluídas foram avaliadas quanto à qualidade metodológica através da ferramenta AMSTAR. A principal medida estudada foi a intensidade de dor. Foram encontrados 227 estudos e com base nos critérios de inclusão e exclusão, 32 artigos foram lidos na íntegra, tendo sido excluído um por não avaliar a dor. As desordens musculoesqueléticas corresponderam a 70,96% das doenças avaliadas e a escala analógica visual (EAV) foi a única ferramenta de mensuração da dor utilizada em 100% dos estudos. Aproximadamente 57% dos estudos tinham alta qualidade metodológica (PEDro=7). Em 53,84% dos ensaios o LAI foi utilizado como intervenção única, e em 46,16% foi associado a exercícios. Em 96,15% dos ensaios clínicos e 100% das revisões sistemáticas, o LAI promoveu alívio da dor. CONCLUSÃO: O LAI é uma modalidade eficaz para analgesia ao promover significativo alívio da dor, rápida recuperação e melhora na qualidade de vida dos pacientes de forma segura. A diversidade nos parâmetros de irradiação (dose, duração, intervalo e número de sessões) empregados, indica a necessidade de mais estudos randomizados para estabelecer sua eficiência em longo prazo.

Tratamiento con radiación láser de baja potencia en pacientes con estomatitis aftosa recurrente

Fundamento entre las urgencias periodontales que requieren atención inmediata está la estomatitis aftosa recurrente, debido a las molestias o complicaciones que ocasiona al paciente. El empleo de la radiación láser de baja potencia puede resultar efectivo en el tratamiento de esta entidad. Objetivo determinar el efecto terapéutico del tratamiento con radiación láser de baja potencia en pacientes con diagnóstico de estomatitis aftosa recurrente. Métodos estudio descriptivo, transversal, realizado en el periodo mayo/2019-mayo/2021, en el servicio estomatológico del policlínico Dr. Enrique Barnet, del municipio de Lajas, provincia de Cienfuegos, que incluyó a 46 pacientes con diagnóstico de estomatitis aftosa recurrente. Se empleó el análisis de documentos, la observación y el cuestionario; además del examen bucal como método diagnóstico. Los pacientes recibieron tratamiento con radiación láser de baja potencia. Se aplicó el programa EPIDAT 3.1 para el procesamiento estadístico de los datos. Resultados predominó el sexo femenino, la edad entre 19-34 años, así como las úlceras aftosas menores. Las lesiones se localizaron principalmente en labio. El 97,83 % de los pacientes refirió remisión de la lesión al quinto día de tratamiento. Todos los pacientes tratados evolucionaron favorablemente hacia la cicatrización. Solo un paciente presentó reacciones adversas. Conclusiones los resultados permitieron constatar los beneficios terapéuticos de la terapia con láser de baja potencia en el tratamiento de la estomatitis aftosa recurrente.

Background among the periodontal emergencies that require immediate attention is the RAS, due to the inconvenience or complications that it causes to the patient. The use of low power laser radiation can be effective in the treatment of this entity. Objective to determine the therapeutic effect of treatment with low-power laser radiation in patients diagnosed with recurrent aphthous stomatitis. Methods descriptive, cross-sectional study, carried out from May/2019 to May/2021, in the Dr. Enrique Barnet polyclinic's dental service, in Lajas municipality, Cienfuegos province, which included 46 patients diagnosed with recurrent aphthous stomatitis. Document analysis, observation and questionnaire were used; in addition to the oral examination as a diagnostic method. Patients received treatment with low-power laser radiation. The EPIDAT 3.1 program was applied for the statistical data processing. Results the female sex predominated, the age between 19-34 years, as well as minor aphthous ulcers. The lesions were located mainly on the lip. 97.83% of the patients reported remission of the lesion on the fifth day of treatment. All treated patients evolved favorably towards healing. Only one patient presented adverse reactions. Conclusions the results allowed us to verify the therapeutic benefits of low power laser therapy in the treatment of recurrent aphthous stomatitis.

Efeitos clínicos da fotobiomodulação como terapia adjuvante não-cirúrgica na periodontite crônica: uma revisão integrativa da literatura / Clinical effects of photobiomodulation as non-surgical adjuvant therapy for chronic periodontitis: an integrative literature review

Introdução: A doença periodontal, de origem infecciosa, constitui diferentes quadros clínicos de caráter multifatorial e inflamatório. A fotobiomodulação é uma técnica não invasiva que tem demonstrado ser capaz de diminuir a inflamação e proporcionar alívio da dor. Estudos também demonstraram que a adoção da fotobiomodulação adjuvante à raspagem e alisamento radicular tem sido capaz de reduzir a carga bacteriana proveniente da periodontite crônica. Objetivos: Analisar os efeitos da fotobiomodulação como terapia adjuvante à raspagem e ao alisamento radicular no tratamento da periodontite crônica publicados nos últimos cinco anos. Métodos: Trata-se de uma revisão integrativa da literatura, realizada no período de setembro a novembro de 2021, mediante a utilização dos seguintes descritores: "Periodontitis", "Photobiomodulation" e "Therapy, selecionando artigos publicados em inglês durante o período entre 2016 a 2021. Resultados: Foram identificados 47 trabalhos. Destes, foram excluídos 39 estudos que se dispersaram do tema e 2 que se encontravam indisponíveis para o acesso, resultando em 6 artigos que foram consultados integralmente. Foi consenso entre os artigos consultados que a prática da fotobiomodulação tornou-se um potencial agente terapêutico no tratamento da periodontite crônica contribuindo para a redução da contagem de periodontopatógenos e que atua de maneira coadjuvante às raspagens radiculares. Conclusão: A fotobiomodulação mostrou-se uma ferramenta promissora na área odontológica. Entretanto, a grande variedade nos parâmetros de tratamentos e protocolos utilizados na fotobiomodulação impossibilita uma comparação e uma análise mais crítica e rigorosa dos resultados obtidos nos trabalhos analisados.

Introduction: Periodontal disease, which has an infectious origin, constitutes a multifactorial and inflammatory different clinical condition of multifactorial, inflammatory, and infectious origin. Photobiomodulation is a non-invasive technique that has been shown to decrease inflammation and provide pain relief. Studies also have shown that the choosing of photobiomodulation as adjuvant therapy to scaling and root planing has been able to reduce the bacterial load from chronic periodontitis. Objectives: To analyze the effects of photobiomodulation as an adjuvant therapy to scaling and root planing in the treatment of chronic periodontitis in the studies published in the last five years. Methods: This is an integrative literature review, carried out from September to November 2021, using the following descriptors: "Periodontitis", "Photobiomodulation" and "Therapy, from selected articles published in English during the period between 2016 to 2021. Results: From the research and selection of studies to compose this integrative literature review, 47 studies were initially identified based on the descriptors. From those, 39 papers that were outside from the topic and 2 papers that were unavailable for access were excluded from the present review. Then remained, 6 articles that were fully consulted. The practice of photobiomodulation has become a potential therapeutic agent in the treatment of chronic periodontitis reducing the count of periodontopathogens and as an adjunct therapy to root scaling. Conclusion: Photobiomodulation therapy has become a promising tool in the dental field, however, the great variety in the treatment parameters and protocols used for photobiomodulation makes impossible to compare and perform a more critical and rigorous analysis of the results collected in the present work.

Analysis of risk factors of radiation-induced toxicity in limited-stage small cell lung cancer treated with hypofractionated intensity-modulated radiotherapy / 中华肿瘤杂志

Objective: To compare the incidence of radiation-related toxicities between conventional and hypofractionated intensity-modulated radiation therapy (IMRT) for limited-stage small cell lung cancer (SCLC), and to explore the risk factors of hypofractionated radiotherapy-induced toxicities. Methods: Data were retrospectively collected from consecutive limited-stage SCLC patients treated with definitive concurrent chemoradiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from March 2016 to April 2022. The enrolled patients were divided into two groups according to radiation fractionated regimens. Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) was used to evaluate the grade of radiation esophagus injuries and lung injuries. Logistic regression analyses were used to identify factors associated with radiation-related toxicities in the hypofractionated radiotherapy group. Results: Among 211 enrolled patients, 108 cases underwent conventional IMRT and 103 patients received hypofractionated IMRT. The cumulative incidences of acute esophagitis grade ≥2 [38.9% (42/108) vs 35.0% (36/103), P=0.895] and grade ≥ 3 [1.9% (2/108) vs 5.8% (6/103), P=0.132] were similar between conventional and hypofractionated IMRT group. Late esophagus injuries grade ≥2 occurred in one patient in either group. No differences in the cumulative incidence of acute pneumonitis grade ≥2[12.0% (13/108) vs 5.8% (6/103), P=0.172] and late lung injuries grade ≥2[5.6% (6/108) vs 10.7% (11/103), P=0.277] were observed. There was no grade ≥3 lung injuries occurred in either group. Using multiple regression analysis, mean esophageal dose ≥13 Gy (OR=3.33, 95% CI: 1.23-9.01, P=0.018) and the overlapping volume between planning target volume (PTV) and esophageal ≥8 cm(3)(OR=3.99, 95% CI: 1.24-12.79, P=0.020) were identified as the independent risk factors associated with acute esophagitis grade ≥2 in the hypofractionated radiotherapy group. Acute pneumonitis grade ≥2 was correlated with presence of chronic obstructive pulmonary disease (COPD, P=0.025). Late lung injuries grade ≥2 was correlated with tumor location(P=0.036). Conclusions: Hypofractionated IMRT are tolerated with manageable toxicities for limited-stage SCLC patients treated with IMRT. Mean esophageal dose and the overlapping volume between PTV and esophageal are independently predictive factors of acute esophagitis grade ≥2, and COPD and tumor location are valuable factors of lung injuries for limited-stage SCLC patients receiving hyofractionated radiotherapy. Prospective studies are needed to confirm these results.

Second allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning and donor changes in relapsed hematological malignancies after the first allogeneic transplant / 中华血液学杂志

Objective: The purpose of this study was to assess the safety and efficacy of a second allogeneic hematopoietic stem cell transplantation (allo-HSCT) with reduced-intensity conditioning (RIC) in patients with hematological malignancies who had relapsed after the first allo-HSCT. Methods: Between April 2018 and June 2021, 44 patients with hematological malignancies (B-ALL 23, T-ALL/T-LBL 4, AML15, and MDS 2) were enrolled and retrospectively examined. Unrelated donors (n=12) or haploidentical donors (n=32) were used. Donors were replaced in all patients for the second allo-HSCT. Hematological and immunological germline predisposition genes and hematopoietic and immune function tests were used to select the best-related donor. Total body irradiation (TBI) /fludarabine (FLU) -based (n=38), busulfan (BU) /FLU-based (n=4), total marrow irradiation (TMI) /FLU-based (n=1), and BU/cladribine-based (n=1) were the RIC regimens used. For graft versus host disease (GVHD) prevention, cyclosporine, mycophenolate mofetil, short-term methotrexate, and ATG were used. Eighteen (40.9%) of 44 patients with gene variations for which targeted medications are available underwent post-transplant maintenance therapy. Results: The median age was 25 years old (range: 7-55). The median interval between the first and second HSCT was 19.5 months (range: 6-77). Before the second allo-HSCT, 33 (75%) of the patients were in complete remission (CR), whereas 11 (25%) were not. All patients had long-term engraftment. The grade Ⅱ-Ⅳ GVHD and severe acute GVHD rates were 20.5% and 9.1%, respectively. Chronic GVHD was found in 20.5% of limited patterns and 22.7% of severe patterns. CMV and EBV reactivation rates were 29.5% and 6.8%, respectively. Hemorrhage cystitis occurred in 15.9% of cases, grade Ⅰ or Ⅱ. The 1-yr disease-free survival (DFS), overall survival (OS), and cumulative recurrence incidence (RI) rates of all patients were 72.5% (95% CI, 54.5%-84.3%), 80.6% (95% CI, 63.4%-90.3%), and 25.1% (95% CI, 13.7%-43.2%), respectively, with a median follow-up of 14 (2-39) months. There were eight deaths (seven relapses and one infection). The rate of non-relapse mortality (NRM) was only 2.3%. The CR patients' 1-yr RI rate was significantly lower than the NR patients (16.8% vs 48.1%, P=0.026). The DFS rate in CR patients was greater than in NR patients, although there was no statistical difference (79.9% vs 51.9%, P=0.072). Univariate analysis revealed that CR before the second allo-HSCT was an important prognostic factor. Conclusion: With our RIC regimens, donor change, and post-transplant maintenance therapy, the second allo-HSCT in relapsed hematological malignancies after the first allo-HSCT is a safe and effective treatment with high OS and DFS and low NRM and relapse rate. The most important factor influencing the prognosis of the second allo-HSCT is the patient's illness condition before the transplant.

Research progress on the bone-marrow sparing intensity-modulated radiotherapy for cervical cancer / 中华放射肿瘤学杂志

The cisplatin-based concurrent chemoradiotherapy (CCRT) has been accepted as a standard treatment for most locally advanced cervical cancer. Compared with radiation therapy alone, CCRT can increase tumor control and survival rates, whereas it also can increase the incidence of acute hematological toxicity, which results in the treatment interruption or delay, and may even affect clinical efficacy and prognosis of patients. Therefore, how to reduce the incidence and severity of acute hematological toxicity induced by CCRT is a hot spot of clinical research. Previous studies have demonstrated that the occurrence of hematological toxicity is associated with the volume and dose of irradiated pelvic bone marrow. With the development of modern radiotherapy technology, precise radiotherapy technologies, such as intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT), not only guaranteed the enough dose for tumor, but also realized the protection of normal tissues. This article will focus on the feasibility of bone marrow sparing during CCRT for cervical cancer, and summarize the research progress in recent years.

Correlation between monitor units and pass rate of plan dose verification in VMAT plan for different cancers / 中华放射肿瘤学杂志

Objective:To analyze the correlation between the monitor units and pass rate of plan dose verification in the volumetric intensity modulated arc therapy (VMAT) plan.Methods:VMAT plans for 20 patients with nasopharyngeal carcinoma (NPC) and 30 patients with cervical cancer who underwent radiotherapy at Liuzhou Workers' Hospital from January to October 2020 were retrospectively chosen. The Detector 1500 array and Octavius 4D phantom from German PTW company were used for dose measurement. The pass rates of dose verification of relevant plans were analyzed under the conditions of 3%/2 mm and 2%/2 mm. The correlation between the monitor units and pass rate of plan dose verification in VMAT plans was assessed by Pearson's bivariate correlation analysis.Results:Under the condition of 3%/2 mm, the correlation coefficients between the monitor units and gamma pass rate were -0.873 ( P<0.001), -0.800 ( P<0.001), -0.781 ( P<0.001), -0.493 ( P=0.006) for NPC_1Arc, NPC_2Arc, NPC_1Arc+NPC_2Arc and Cervix_2Arc, respectively. Under the condition of 2%/2 mm, the correlation coefficients between the monitor units and gamma pass rate were -0.842 ( P<0.001), -0.770 ( P<0.001), -0.748 ( P<0.001) and -0.531 ( P=0.003) for NPC_1Arc, NPC_2Arc, NPC_1Arc+NPC_2Arc and Cervix_2Arc, respectively. Conclusion:Significant negative correlation can be observed between the monitor units and plan dose verification pass rate in VMAT plan.

Phase II trial of hippocampal avoidance whole-brain irradiation with simultaneous integrated boost for treatment of brain metastases of lung cancer / 中华放射肿瘤学杂志

Objective:To evaluate the efficacy and safety of hippocampal avoidance whole-brain irradiation with simultaneous integrated boost in the treatment of brain metastases of lung cancer.Methods:Forty lung cancer patients with brain metastases who received whole-brain radiotherapy with simultaneous integrated boost and hippocampal avoidance in Cancer Hospital, Chinese Academy of Medical Sciences from 2014 to 2020 were enrolled in this study. Brain MRI, survival follow-up and evaluation of side effects were performed before radiotherapy and at 1, 3, 6 and 12 months after radiotherapy, respectively. Overall survival (OS), progression-free survival (PFS) and changes in cognitive function were analyzed. Continuous data were described as Mean ± SD. Categorical data were described by frequency and composition ratio or percentage. Survival analysis was conducted by Kaplan-Meier method. Influencing factors of survival were identified by univariate and multivariate Cox's regression analyses.Results:A total of 40 patients were enrolled in the study. The median follow-up time was 14.2 months and the median OS, PFS and intracranial PFS of all patients were 14.8 months, 6.7 months and 14.8 months, respectively. Multivariate analysis showed that male gender and newly diagnosed stage Ⅳ disease were associated with worse OS and PFS, respectively. The Hopkins verbal learning test-revised (HVLT-R) scores at baseline and 1, 3 and 6 months after radiotherapy were 21.94±2.99, 20.88±3.12, 20.03±3.14, and 19.78±2.98, respectively. The HVLT-R score at 6 months after radiotherapy was decreased by approximately 9.8% compared with the baseline. No grade 3 or above toxic and side effect occurred in the entire cohort.Conclusion:Hippocampal avoidance whole-brain irradiation with simultaneous integrated boost is a safe and effective treatment for brain metastases of lung cancer, which is expected to reduce the impact of radiotherapy on cognitive function.

Correlation between acute intestinal toxicity and dose-volume parameters in patients with cervical cancer receiving postoperative adjuvant radiotherapy / 中华放射肿瘤学杂志

Objective:To identify dose-volume parameters to predict the incidence of acute intestinal toxicity in cervical cancer patients after postoperative adjuvant radiotherapy.Methods:Clinical data of 93 cervical cancer patients who underwent postoperative adjuvant intensity-modulated radiotherapy (IMRT) were retrospectively evaluated. The dose-volume parameters comprised the absolute volume of the bowel receiving 5-45 Gy (5 Gy interval) radiation dose and the total volume of the bowel. The acute radiation-induced intestinal toxicity was evaluated by Radiation Therapy Oncology Group (RTOG) criteria. The association between the irradiated bowel volume and acute intestinal toxicity was analyzed.Results:A total of 26 (28%) patients experienced grade ≥2 acute intestinal toxicity. A strong relationship between grade ≥2 acute intestinal toxicity and the irradiated small bowel volume was observed at the total volume of small bowel, small bowel V 5 Gy, V 10 Gy and V 15 Gy (all P<0.05). Small bowel V 10 Gy ( HR=1.028, 95% CI, 0.993-1.062, P=0.029) and small bowel ?V 15 Gy( HR=0.991, 95% CI, 0.969-1.013, P=0.034)were the independent risk factors for evident acute intestinal toxicity. Conclusion:Dose-volume parameters of the small bowel can be used as predictors for the occurrence of grade ≥2 acute intestinal toxicity in cervical cancer patients undergoing postoperative adjuvant radiotherapy.

Radiomics-based prediction of gamma pass rates for different intensity-modulated radiation therapy techniques for pelvic tumors / 中华放射医学与防护杂志

Objective:To explore the feasibility of a classification prediction model for gamma pass rates (GPRs) under different intensity-modulated radiation therapy techniques for pelvic tumors using a radiomics-based machine learning approach, and compare the classification performance of four integrated tree models.Methods:With a retrospective collection of 409 plans using different IMRT techniques, the three-dimensional dose validation results were adopted based on modality measurements, with a GPR criterion of 3%/2 mm and 10% dose threshold. Then prediction were built models by extracting radiomics features based on dose documentation. Four machine learning algorithms were used, namely random forest (RF), adaptive boosting (AdaBoost), extreme gradient boosting (XGBoost), and light gradient boosting machine (LightGBM). Their classification performance was evaluated by calculating sensitivity, specificity, F1 score, and AUC value. Results:The RF, AdaBoost, XGBoost, and LightGBM models had sensitivities of 0.96, 0.82, 0.93, and 0.89, specificities of 0.38, 0.54, 0.62, and 0.62, F1 scores of 0.86, 0.81, 0.88, and 0.86, and AUC values of 0.81, 0.77, 0.85, and 0.83, respectively. XGBoost model showed the highest sensitivity, specificity, F1 score, and AUC value, outperforming the other three models. Conclusions:To build a GPR classification prediction model using a radiomics-based machine learning approach is feasible for plans using different intensity-modulated radiotherapy techniques for pelvic tumors, providing a basis for future multi-institutional collaborative research on GPR prediction.

The efficacy analysis of moderately hypofractionated IMRT combined with androgen deprivation therapy for locally advanced prostate cancer / 中华放射医学与防护杂志

Objective:To investigate the efficacy and adverse reactions of moderately hypofractionated intensity modulated radiation therapy (IMRT) combined with androgen deprivation therapy (ADT) for locally advanced prostate cancer (LAPC).Methods:This study retrospectively analyzed the medical records of 40 LAPC patients who were admitted in The Second Hospital of Dalian Medical University during 2014-2020. The planning gross target volume (PGTV) dose for prostate gland and seminal vesicle gland was 64.8-70.0 Gy/25-28 f, 2.4-2.8 Gy/f and the dose of PGTVnd in 20 cases with positive pelvic lymph nodes was 60.0-64.4 Gy/25-28 f, 2.3-2.4 Gy/f. The dose of planning target volume (PTV) for the drainage area of pelvic lymph nodes was 45.0-50.4 Gy/25-28 f. The enrolled patients were treated with long-term ADT, including neoadjuvant, simultaneous, and adjuvant therapies. The efficacy and adverse reactions were evaluated. The prognostic factors affecting the biochemical failure-free survival (BFFS) were analyzed.Results:The median follow-up time was 31 months. The 2- and 3-year overall survival (OS) rates were 100% and 96.9%, respectively. The 1-, 2-, and 3-year BFFS rates were 90%, 76.8% and 72%, respectively. The 1-, 2-, and 3-year distant metastasis-free survival (DMFS) rates were 92.2%, 82.8% and 75.1%, respectively. Gleason (GS) score ( χ2=10.00, P < 0.05) and adjacent tissue invasion ( χ2=8.85, P<0.05) were prognostic factors related to BFFS for LAPC. Adjacent tissue invasion and GS 9-10 were independent poor prognostic factors. The incidence of acute urinary adverse reaction and rectal injury (grade≥2) was 7.5% and 20%, respectively. The incidence of late urinary adverse reaction and rectal injury (grade≥2) was 12.5% and 17.5%, respectively. Adverse reactions at grade 3-4 did not occur. Conclusions:The moderately hypofractionated IMRT combined with ADT is feasible for LAPC treatment, achieving satisfactory survival effects. 70 Gy/25-28 f, 2.5-2.8 Gy/f is a safe and effective moderate hypofraction scheme. Adjacent tissue invasion and GS score are prognostic factors related to BFFS for LAPC.

Effects of Onodera′s prognostic nutritional index on the prognosis of locally advanced oropharyngeal squamous cell carcinoma after induction chemotherapy followed by sequential chemoradiotherapy / 中华放射医学与防护杂志

Objective:To explore the effects of Onodera′s prognostic nutritional index (PNI) on the prognosis of locally advanced oropharyngeal squamous cell carcinoma (LA-OPSCC) after induction chemotherapy followed by sequential chemoradiotherapy.Methods:A retrospective analysis was conducted on the clinical data of 52 LA-OPSCC patients receiving induction chemotherapy followed by sequential chemoradiotherapy in The Affiliated Cancer Hospital of Guizhou Medical University during 2014-2018. The PNI values of all the patients at different treatment phases were statistically analyzed, and the ROC curve was employed to determine the optimal critical value of PNI. The patients in this study were divided into a well-nourished group ( n = 27) and a poorly-nourished group ( n = 25). The Kaplan-Meier method was used for survival analysis. The Cox proportional hazards model was utilized to analyze the relationships between different nutritional status and prognosis. Clinical features and adverse reactions were compared between the two groups. Results:The PNI values decreased significantly after radiotherapy, with an optimal critical value of 42.4. The 5-year overall survival (OS) and progression-free survival (PFS) of the well-nourished group (PNI ≥ 42.4) were 62.6% and 60.9%, respectively, which were significantly higher than those (30.1% and 29.7%) of the poorly-nourished group (PNI < 42.4, χ2 = 11.12, 5.74, P < 0.05). The multivariate analysis showed that PNI was an independent prognostic factor for the OS after radiotherapy ( HR = 2.752, 95% CI: 1.095-6.917, P = 0.031). The LA-OPSCC patients aged over 60 years or those who did not respond to induction chemotherapy accounted for a higher proportion of malnutrition after chemoradiotherapy ( χ2 = 4.89, 5.05, P < 0.05). Conclusions:PNI after radiotherapy can be used as a prognostic factor in the evaluation of LA-OPSCC patients receiving induction chemotherapy followed by sequential chemoradiotherapy. The LA-OPSCC patients aged over 60 years or those who do not respond to induction chemotherapy should receive more nutritional support during the chemoradiotherapy.

Prediction of radiomics-based machine learning in dose verification of intensity-modulated pelvic radiotherapy / 中华放射医学与防护杂志

Objective:Based on radiomics characteristics, different machine learning classification models are constructed to predict the gamma pass rate of dose verification in intensity-modulated radiotherapy for pelvic tumors, and to explore the best prediction model.Methods:The results of three-dimensional dose verification based on phantom measurement were retrospectively analyzed in 196 patients with pelvic tumor intensity-modulated radiotherapy plans. The gamma pass rate standard was 3%/2 mm and 10% dose threshold. Prediction models were constructed by extracting radiomic features based on dose documentation. Four machine learning algorithms, random forest, support vector machine, adaptive boosting, and gradient boosting decision tree were used to calculate the AUC value, sensitivity, and specificity respectively. The classification performance of the four prediction models was evaluated.Results:The sensitivity and specificity of the random forest, support vector machine, adaptive boosting, and gradient boosting decision tree models were 0.93, 0.85, 0.93, 0.96, 0.38, 0.69, 0.46, and 0.46, respectively. The AUC values were 0.81 and 0.82 for the random forest and adaptive boosting models, respectively, and 0.87 for the support vector machine and gradient boosting decision tree models.Conclusions:Machine learning method based on radiomics can be used to construct a prediction model of gamma pass rate for specific dosimetric verification of pelvic intensity-modulated radiotherapy. The classification performance of the support vector machine model and gradient boosting decision tree model is better than that of the random forest model and adaptive boosting model.

Microbubbles carrying resiquimod enhance HIFU ablation and co-stimulate tumor immune response / 中华超声影像学杂志

Objective:To prepare the resiquimod-loaded lipid microbubbles R848-MBs, evaluate their enhanced ultrasound imaging and high intensity focused ultrasound (HIFU) ablation effects, and explore their ability to improve tumor immune microenvironment synergize with HIFU.Methods:R848-MBs were prepared by the thin film hydration-mechanical shock method; The basic characteristics and safety of R848-MBs were detected, the HIFU controlled-release characteristics were verified in vitro and the drug metabolism and biological distribution were investigated in vivo. The ability of enhancing ultrasound imaging was observed in vitro and in vivo. To investigate the enhanced HIFU ablation effect of R848-MBs, six EMT6 tumor-bearing mice were randomly divided into HIFU group and R848-MBs+ HIFU group, three mice in each group, the changes in contrast average sound intensity before and after ablation in mouse tumor areas and the change of ultrasound image gray value in tumor area were evaluated, the tumor were resected to observe the coagulative necresis by TTC staining and HE staining. Forty-five tumor-bearing mice were randomly divided into control group, Free R848 group, HIFU group, Blank-MBs+ HIFU group and R848-MBs+ HIFU group, nine mice in each group. On the third day after treatment, 3 mice in each group were randomly selected and killed, to evaluate the ability of R848-MBs to improve tumor immune microenvironment synergize with HIFU. The expression level of CRT on the surface of tumor cells were detected by immunofluorescence staining, the proportion of mature DC in lymph nodes, spleen, and CD8 + T cells in spleen were detected by flow cytometry. The treatment effectiveness of each group( n=6) were evaluated by measuring tumor volume, observing and drawing survival curves. Results:The R848-MBs lipid microbubbles with good safety were successfully prepared, with a concentration of 2.58×10 9/ml, as spherical bubbles under optical microscope and laser confocal microscopy, in a particle size of (1.72±0.11)μm, at a surface potential of (-10.16±0.73)mV. The cumulative drug release was up to 83.44% after HIFU (90 W, 3 s) in vitro. The concentration of R848 in plasma decreased rapidly, and the drug concentration in tumor tissue of the R848-MBs+ HIFU group was higher than that of the R848 group 24 hours after treatment ( P<0.01). The ultrasound imaging of R848-MBs was significantly enhanced in contrast mode in vitro and in vivo; R848-MBs can significantly enhance the HIFU ablation effect, the contrast average sound intensity change in the tumor area before and after ablation in the R848MBs+ HIFU group was greater than that in the R848 group ( P<0.05), and the immediate ultrasound grayscale value change in the HIFU+ R848-MBs group was 46.34±3.21, which was significantly greater than that in the HIFU group (10.67±1.53), with statistical significance ( P<0.000 1). Coagulation necrosis was observed in tumor HE staining and TTC staining. The results of treatment efficacy in vivo showed that R848-MBs+ HIFU group had the strongest therapeutic effect, and R848-MBs combined with HIFU treatment could significantly prolong the survival period of mice compared with intravenous injection of free R848 ( P<0.01). Immunofluorescence staining and flow cytometry results showed an increase in the expression level of CRT on the surface of tumor tissue in the R848-MBs combined with HIFU group, and the percentage of mature DC in tumor draining lymph nodes (58.53±1.04)% were significantly higher than those in the HIFU group (37.56±2.13)% ( P<0.001), and the percentage of mature DC in the spleen (70.65±1.91)% were significantly higher than those in the HIFU group (36.46±3.89)% ( P<0.001), the percentage of CD8 + T cells in the spleen (27.46±3.04)% was significantly higher than that in the HIFU group (18.69±0.29)% ( P<0.01). Conclusions:The HIFU controlled-release lipid microbubbles R848-MBs can not only enhance the efficiency of HIFU ablation, but also improve the tumor immune microenvironment.

Apoptosis-promoting effect of temozolomide loaded nanoparticles combined with low intensity focused ultrasound on human glioma cells / 中华超声影像学杂志

Objective:To prepare liquid-gas phase modified nanoparticles (TMZ/PFP/PLGA NPs) of perfluoropentane (PFP) and temozolomide (TMZ) encapsulated by polylactic-glycolic acid copolymer (PLGA), combined with low intensity focused ultrasound (LIFU) irradiation, and to investigate its ultrasound imaging ability and intervention effect on human glioma cells in vitro.Methods:TMZ/PFP/PLGA NPs were prepared by compound emulsion method. The basic physical and chemical properties and drug loading ability of TMZ/PFP/PLGA NPs were detected. CCK-8 assay was used to detect the cytotoxicity of nanoparticles in vitro and the effect of synergistic intervention with LIFU on the survival rate of glioma cells. The expression levels of apoptosis related proteins Bcl-2, Bax and caspase-3 were detected by Western blot.Results:Under transmission electron microscope, TMZ/PFP/PLGA NPs showed a circular core-shell structure with regular morphology, particle size was (137.9±63.31)nm, encapsulation efficiency of TMZ was (83.01±5.57)%, drug loading was (3.19±0.22)%. The survival rate of U251 cells was still above 70% after 24 hours of co-incubation with nanoparticles. Under the synergistic effect of LIFU irradiation, the apoptosis of U251 cells was accelerated and the survival rate of U251 cells was significantly decreased. The results of Western blot showed that the synergic intervention could significantly down-regulate the expression of apoptosis related protein Bcl-2, and significantly up-regulate the expression of Bax protein and caspase-3 protein (all P<0.05). Conclusions:TMZ/PFP/PLGA NPs have good basic physical and chemical properties. TMZ/PFP/PLGA NPs have low cytotoxicity in vitro while efficiently loading chemotherapeutic drug timozolomide. Synergistic intervention under LIFU irradiation can significantly accelerate the apoptosis of U251 glioma cells, which has a good application prospect.