Cuidado de Enfermagem à Pessoa com Paraplegia à Luz de Betty Neuman / Nursing Care for the Person with Paraplegia in the Light of Betty Neuman / Cuidados de enfermería a la persona con paraplejia a la luz de Betty Neuman

Objetivo: Relatar e compreender o cuidado de enfermagem à pessoa com paraplegia secundária a acidente automobilístico. Método:Estudo qualitativo descritivo, tipo relato de caso, realizado em hospital público de Feira de Santana/BA. Procedeu-se à entrevista, com uma participante em situação de paraplegia. Utilizou-se a elaboração da SAE e suas etapas considerando os aspectos da Teoria de Betty Neuman. Resultados:O relato da paciente e informações obtidas em prontuário demonstraram desinformações e condutas soltas que dificultam o cuidado, alimentavam sentimento de angústia e tristeza à paciente. Conclusão:proporcionou o entendimento acerca do indivíduo vítima de politrauma e suas necessidades, entendendo o adoecer com transcurso multifatorial onde segundo a teoria de Betty Neuman o ambiente e o indivíduo dialogam entre si surtindo efeito positivo e negativo sob o equilíbrio do corpo humano

Objective: To report and understand nursing care for individuals with paraplegia secondary to car accidents. Method:Descriptive qualitative study, in the form of a case report, conducted at a public hospital in Feira de Santana/BA. An interview was conducted with a participant in a paraplegic situation. The Nursing Process (NP) was developed, and its stages were considered, taking into account aspects of Betty Neuman's Theory. Results:The patient's account and information obtained from medical records revealed misinformation and disjointed behaviors that hindered care, fostering feelings of anguish and sadness in the patient. Conclusion:This study provided an understanding of individuals suffering from polytrauma and their needs, understanding illness as a multifactorial process where, according to Betty Neuman's theory, the environment and the individual interact, having both positive and negative effects on the balance of the human body.

Objetivo: Informar y comprender el cuidado de enfermería para personas con paraplejia secundaria a accidentes automovilísticos. Método:Estudio cualitativo descriptivo, tipo informe de caso, llevado a cabo en un hospital público en Feira de Santana/BA. Se realizó una entrevista con una participante en situación de paraplejia. Se utilizó el desarrollo del Proceso de Enfermería (PE) y sus etapas considerando los aspectos de la Teoría de Betty Neuman. Resultados:El relato de la paciente y la información obtenida de los registros médicos revelaron desinformación y conductas desarticuladas que dificultaron el cuidado, fomentando sentimientos de angustia y tristeza en la paciente. Conclusión:Este estudio proporcionó una comprensión de las necesidades de individuos que sufren politraumatismos, entendiendo la enfermedad como un proceso multifactorial donde, según la teoría de Betty Neuman, el entorno y el individuo interactúan, teniendo efectos tanto positivos como negativos en el equilibrio del cuerpo humano.

Research progress and potential medical applications of anaplastic lymphoma kinase in treatment of non-small cell lung cancer / 中国药理学通报

During the treatment of non-small cell lung cancer ( NSCLC) , many patients have developed drug resistance due to the use of targeted EGFR inhibitors. The main reasons for drug resistance are EGFR site mutations and bypass activation. Activation of ALK pathway is one of the major types of bypass activation. A recent authoritative study indicates that ALK is closely related to immunotherapy. This article reviews the treatment of ALK in tumors from three aspects: the structure and physiological function of ALK, the small molecule inhibitor of ALK, the biological function of ALK and its related treatment methods for NSCLC, and prospects future directions for better application of ALK in the treatment of NSCLC.

Application of immunotherapy in relapsed/refractory B-cell acute lymphoblastic leukemia / 中国药房

Immunotherapy， as an emerging treatment method， has been proven to improve the prognosis of patients with relapsed/refractory B-cell acute lymphoblastic leukemia （B-ALL） and has good application prospects. Immunotherapy， including chimeric antigen receptor T cell immunotherapy （CAR-T） and monoclonal antibodies， has shown great potential for application， and has been approved for marketing. This article summarizes the application of the above two therapies in the treatment of relapsed/ refractory B-ALL， and concludes that CAR-T is a kind of personalized immunotherapy， and the selection of ideal targets is an important part of its action. Currently， the ideal targets in clinical studies include CD19， CD22 and CD19/CD22. Monoclonal antibodies， including blinatumomab and inotuzumab ozogamicin， have shown superior therapeutic efficacy for relapsed/refractory B- ALL. Immunotherapy has shown superior therapeutic effects compared to conventional chemotherapy， expanding the selection of treatment options for relapsed/refractory B-ALL.

Análisis de mutaciones BRAF y NRAS de tumores tiroideos en pacientes de Argentina / Analysis of BRAF and NRAS mutations in thyroid tumors in patients from Argentina

Resumen Introducción : Se ha descrito que alteraciones molecu lares de las células foliculares tiroideas en el gen BRAF o en NRAS están asociadas con el proceso de carcinogé nesis. Nuestro objetivo fue conocer la frecuencia muta cional de BRAF y NRAS a partir de muestras de punción aspirativa con aguja fina (PAAF) en nuestra población. Métodos : Se analizó por qPCR el estado mutacional de BRAF (codón 600) y NRAS (codón 61) de 193 mues tras obtenidas por PAAF de nódulos sospechosos y se comparó con los datos de la anatomía patológica de 115 pacientes. Resultados : La mutación BRAF se identificó en 40 muestras (74.1%) de las punciones categorizadas como Bethesda VI (n = 54). En las muestras que se correspon dieron con carcinoma papilar de tiroides (CPT) variante clásica por histología (n = 47), el 70% presentó la muta ción, mientras que en los otros subtipos la prevalencia fue más baja (p = 0.013). En muestras de lesión folicular (n = 36), el 50% de los carcinomas foliculares resultaron positivos para NRAS pero solo el 6.7% de los adenomas presentaron esta variación. La presencia de mutación BRAF y CPT se asociaron con metástasis en los gan glios linfáticos (p = 0.014) y mayor riesgo relativo de recurrencia según el Consenso Argentino Intersocietario (RR = 6.77, p = 0.022). No hubo diferencias significativas entre la mutación de BRAF y otras características de agresividad en CPT. Conclusión : La mutación de BRAF y NRAS se observa en un número significativo de CPT y carcinoma folicular, respectivamente, en nuestra población. La mutación BRAF se correlaciona significativamente con metástasis en los ganglios linfáticos.

Abstract Introduction : Molecular alterations in follicular cells in the BRAF or NRAS genes have been reported to be associated with the process of carcinogenesis. Our aim was to determine the mutational frequency of BRAF and NRAS in fine-needle aspiration (FNA) specimens in our population. Methods : The mutational status of BRAF (codon 600) and NRAS (codon 61) was analysed by qPCR in 193 FNA specimens from suspicious nodules and compared with pathological data of 115 patients. Results : BRAF mutation was identified in 40 samples (74.1%) of FNAs classified as Bethesda VI (n = 54). In samples histologically diagnosed as classic papillary thyroid carcinoma (cPTC, n = 47), mutation was observed in 70% of cases, while in other subtypes the prevalence was lower (p = 0.013). In FNA specimens of follicular lesions (n = 36), positivity for NRAS was found in 50% of the follicular carcinomas (FTCs), but only in 6.7% of adenomas. Finally, there was a significant correlation between BRAF and PTC with lymph-node metastasis (p = 0.014) and increased relative risk of recurrence based on the Argentine Intersociety Consensus (RR = 6.77, p = 0.022). No significant differences were found between BRAF mutation and other features of aggressiveness in PTC. Conclusion : BRAF and NRAS mutations are observed in a significant number of PTCs and FTCs, in our popu lation. There is a significant correlation between BRAF mutation and lymph-node metastasis.

¿Cuándo se reanuda la conducción después del reemplazo total de cadera primario? / When to resume driving after primary total hip arthroplasty?

Resumen: Introducción: la literatura actual relaciona el regreso a la conducción vehicular con múltiples variables. Sin embargo, los datos actuales sobre el tiempo de regreso a la conducción luego de una artroplastía total de cadera (ATC) son diversos e incluso contradictorios. Por lo tanto, nos hemos planteado el objetivo de determinar el tiempo requerido para volver a conducir en un grupo de pacientes sometidos a una ATC primaria mediante un abordaje posterolateral, centrándonos específicamente en vehículos de marcha manual. Material y métodos: hemos estudiado los resultados clínico-funcionales de 112 pacientes sometidos a una ATC primaria entre Enero de 2019 y Enero de 2020 en un hospital de alta complejidad en Cádiz, Andalucía, España. Resultados: la mediana del tiempo de regreso a la conducción fue de tres semanas (RIC 2-4). Hemos identificado que 89.3% de los pacientes pudo volver a conducir antes de la sexta semana posterior a la cirugía. Además, en 92% de los casos, los pacientes se sintieron aún más seguros al conducir después de la ATC que antes de la intervención. Conclusión: consideramos que a la sexta semana de una ATC es seguro reanudar la conducción de un vehículo.

Abstract: Introduction: the current literature relates the return to driving with multiple variables. For various reasons, the current data on the time to return to driving after a total hip arthroplasty (THA) are diverse and even contradictory. We have proposed the objective of determining the time required to drive a manual gear vehicle again in a group of patients who underwent primary THA through a posterolateral approach with focus on manual gear cars. Material and methods: we have studied the functional results of 112 patients who underwent primary THA between January 2019 and January 2020 in a high level in Cadiz, Andalusia, Spain. Results: the median return to driving was three weeks (IQR 2-4). We have identified that 89.3% of the patients were able to drive again before the sixth week after surgery and in 92% of the cases they did so feeling even safer than before the THA. Conclusion: we consider that after the sixth week of an THA it is safe to resume driving a vehicle.

Slum compassionate community: expanding access to palliative care in Brazil / Comunidad de favela compasiva: ampliar el acceso a los cuidados paliativos en Brasil / Comunidade compassiva de favela: ampliando o acesso aos cuidados paliativos no Brasil

ABSTRACT Objective: To describe the implementation of a compassionate community in Rocinha and Vidigal slums, located in the city of Rio de Janeiro. Method: Report on the experience of implementing a Compassionate Community based on the World Health Organization conceptual bases, supported by university extension guidelines. Results: Initially, local leaders and residents were recruited and trained in palliative care. Subsequently, health professionals from different specialties engaged in the project through volunteering. Home visits were instituted in the form of interconsultation and "sponsorships" by residents and health professionals to people in palliative care and family members. Finally, the health care network in the territory was integrated in order to recognize the project as a support network. Conclusion: We highlight the experience as living work in health, which involves relationships and creative processes, which mobilize structured technical knowledge and relationships between people and soft-hard and soft technologies, making it possible to recognize powers in the territory.

RESUMEN Objetivo: Describir la implementación de una comunidad compasiva en las favelas de Rocinha y Vidigal, ubicadas en la ciudad de Río de Janeiro. Método: Relato de la experiencia de implementación de una Comunidad Compasiva a partir de las bases conceptuales de la Organización Mundial de la Salud, sustentada en lineamientos de extensión universitaria. Resultados: Inicialmente, se reclutaron y capacitaron a líderes locales y residentes en cuidados paliativos. Posteriormente, profesionales de la salud de diferentes especialidades se involucraron en el proyecto a través del voluntariado. Se instituyeron visitas domiciliarias en la modalidad de interconsulta y "patrocinios" por parte de residentes y profesionales de salud a personas en cuidados paliativos y familiares. Finalmente, se integró la Red de Atención a la Salud del territorio para reconocer el proyecto como una red de apoyo. Conclusión: Destacamos la experiencia como trabajo vivo en salud, que involucra relaciones y procesos creativos, que movilizan saberes técnicos estructurados y relaciones entre personas y tecnologías ligeras-duras y ligeras, posibilitando el reconocimiento de poderes en el territorio.

RESUMO Objetivo: Descrever a implementação de uma comunidade compassiva nas favelas da Rocinha e Vidigal, localizadas na cidade do Rio de Janeiro. Método: Relato da experiência da implementação de uma Comunidade Compassiva a partir das bases conceituais da Organização Mundial da Saúde, amparada pelas diretrizes da extensão universitária. Resultados: Inicialmente, lideranças locais e moradores foram recrutados e receberam treinamento sobre cuidados paliativos. Posteriormente, profissionais de saúde de diferentes especialidades engajaram-se no projeto por meio da prática do voluntariado. Foram instituídas visitas domiciliares na modalidade interconsulta e "apadrinhamentos" por moradores e profissionais de saúde às pessoas em cuidados paliativos e familiares. Por fim, a Rede de Atenção à Saúde do território foi integrada de forma a reconhecer o projeto como rede de apoio. Conclusão: Destacamos a experiência como trabalho vivo em saúde, que envolve relações e processos criativos, os quais mobilizam o saber técnico estruturado e as relações entre as pessoas e as tecnologias leve-duras e leves, tornando factível o reconhecimento de potências no território.

Migrant women caregivers' experiences in end-of-life formal care / Experiências de mulheres migrantes cuidadoras em cuidados formais no final da vida / Experiencias de cuidadoras migrantes en el cuidado formal al final de la vida

ABSTRACT Objective: To describe and understand the experience of Latin American migrant women as caregivers of elderly people in situations of advanced illness and end of life. Method: Qualitative study using Gadamer's hermeneutic phenomenology. Data were collected in 2019 through 9 semi-structured interviews with Latin American women caregivers, who had cared for people at the end of life, in the Province of Granada (Spain). Results: Two themes emerged: "Migrant caregiver at the end of life" and "And now, what should I do?": the impact of the loss at the economic, emotional and labor level Conclusion: Care during the end of life of the cared person generates an additional overload to the situation of migrant women. The experience of this stage is related to the bond with the persons cared and their families, which may affect the development of complicated grief and personal problems related to the loss of employment and the absence of economic support.

RESUMO Objetivo: Descrever e compreender a experiência de mulheres migrantes latino-americanas, cuidadoras de idosos em situações de doença avançada e de fim da vida. Método: Estudo qualitativo baseado na fenomenologia hermenêutica de Gadamer. Os dados foram coletados em 2019 por meio de 9 entrevistas semiestruturadas com mulheres cuidadoras latino-americanas que cuidaram de pessoas no final da vida em Granada (Espanha). Resultados: Surgiram dois temas: "Cuidador migrante no fim da vida" e "E agora, o que eu faço?": o impacto da perda nos níveis econômico, emocional e de trabalho. Conclusão: O cuidado durante o fim da vida da pessoa cuidada gera uma sobrecarga adicional à situação das mulheres migrantes. A experiência dessa fase está relacionada ao vínculo com a pessoa cuidada e sua família, o que pode ter um impacto na elaboração de luto complicado e problemas pessoais relacionados à perda do emprego e à ausência de apoio econômico.

RESUMEN Objetivo: Describir y comprender la experiencia de las mujeres migrantes latinoamericanas como cuidadoras de personas mayores en situación de enfermedad avanzada y final de la vida. Método: Estudio cualitativo desde la fenomenología hermenéutica de Gadamer. Los datos fueron recogidos en 2019 mediante 9 entrevistas semiestructuradas a cuidadoras latinoamericanas, que hubieran atendido a personas al final de la vida en Granada (España). Resultados: Surgieron 2 temas: "Cuidadora migrante al final de la vida" e "Y ahora ¿qué hago?": El impacto de la pérdida a nivel económico, emocional y laboral. Conclusión: La atención durante el final de la vida de la persona cuidada genera una sobrecarga adicional a la situación de las mujeres migrantes. La vivencia de esta etapa se relaciona con el vínculo con la persona cuidada y su familia, que puede incidir en la elaboración de un duelo complicado y problemas personales relacionados con la pérdida de empleo y la ausencia de apoyo económico.

Monitoreo de las insuficiencias orgánicas en pacientes graves con hemopatías malignas por el uso de las células CAR-T / Monitoring of organ failures in critically ill patients with blood malignancies by the use of CAR - T cell

Introducción: La inmunoterapia con células T modificadas con receptor quimérico antígeno específico es un tratamiento prometedor para hemopatías malignas. Sin embargo, la activación dirigida de la respuesta inmunitaria desata en ciertos casos complicaciones específicas graves y mortales. Objetivos: Describir el monitoreo de las complicaciones por el uso de las células T con receptor antígeno quimérico en pacientes graves con hemopatías malignas. Métodos: Se realizó una investigación bibliográfico documental acerca del tema. Se consultaron las bases de datos de SciELO y PubMed de los últimos cinco años. Conclusiones: Se describieron las complicaciones derivadas de la terapia con células inmunoefectoras, que aumentan el desarrollo de insuficiencias orgánicas, a través del síndrome de liberación de citoquinas y el síndrome de toxicidad neurológica. El tratamiento se basó en establecer medidas de monitorización y soporte, tratamiento con anticonvulsivantes, corticosteroides e ingreso en los servicios de medicina intensiva de forma precoz. Se disminuyó el riesgo en la aparición de complicaciones y muerte con un adecuado monitoreo de las insuficiencias orgánicas derivadas de la inmunoterapia de células T con receptor antígeno quimérico.

Introduction: Immunotherapy with T-cells modified with antigen-specific chimeric receptor is a promising treatment for malignant hemopathies. However, the targeted activation of the immune response in certain cases unleashes specific severe and fatal complications. Objectives: To describe the monitoring of complications from the use of CAR T-cells in critically ill patients with blood malignancies. Methods: A bibliographical-documentary research on the subject was carried out. The SciELO and Pubmed databases of the last five years were consulted. Conclusions: Complications derived from the therapy with immunoeffector cells are described, which increase the development of organ failures, through the cytokine release syndrome and the neurological toxicity syndrome. Treatment is based on monitoring and support measures, treatment with anticonvulsants, corticosteroids, and early admission to intensive care. With adequate monitoring of organ failure derived from chimeric antigen receptor T-cell immunotherapy, a decreased risk of complications and death in these patients was carried out.

Inibidores epigenéticos como reguladores de linfócitos T CD8+ humanos / Epigenetic inhibitors as regulators of human CD8 T lymphocytes

Linfócitos T CD8 são células chave na resposta antitumoral. Uma vez ativadas, sofrem mudanças epigenéticas, adquirem fenótipos distintos e sua função está ligada ao potencial citotóxico e produção de mediadores inflamatórios. Porém, na resposta antitumoral, tais células encontram-se disfuncionais. Assim, estratégias capazes de reprogramar as células TCD8 podem aumentar sua eficácia. Inibidores epigenéticos são capazes de modular o perfil de células T CD4, mas os efeitos em células T CD8 ainda não estão totalmente esclarecidos. Portanto, buscamos identificar possíveis inibidores epigenéticos que sejam capazes de modular a atividade e o perfil fenotípico de linfócitos T CD8. Para tal, células T CD8 foram isoladas por sorting a partir de PBMC de doadores saudáveis e cultivados em placas de 96 poços na presença de coquetel de ativação (DynaBeads anti-CD3/CD28, IFN- e IL-2 recombinantes) e 1µM de diferentes inibidores epigenéticos (MS023, A485, L-MOSES, A-196, GSKLSD1, A366). Linfócitos T CD8 não estimulados e linfócitos T CD8 ativados na ausência de inibidores epigenéticos foram utilizados como controles. Após 4 ou 8 dias de cultura, as células foram coletadas e analisadas por citometria de fluxo para avaliação de marcadores ligados à ativação (CD69), função (IFN- e granzima B), diferenciação (CCR7, CD45RA) e exaustão (PD-1, TIGIT). As células foram adquiridas no citômetro de fluxo BD FACSymphony A5, e a análise estatística foi feita através do software GraphPad Prism 9. Realizamos ensaios in vitro nos quais células T CD8 foram ativadas na presença ou não de diferentes inibidores, com um deles apresentando intenso potencial de modular células T CD8: o A485, um inibidor seletivo do bromodomínio p300/CBP. Os nossos dados mostram que o A485 aumentou a ativação celular, evidenciado pelo aumento da frequência de células TCD8+CD69+. Este inibidor também foi capaz de modular o fenótipo de memória das células T, polarizando-as para um perfil TN/TSCM, diferentemente do controle e dos outros inibidores, que induziram um perfil TEM (células T efetoras de memória). Após oito dias, o tratamento com o inibidor A485 resultou em menor frequência de células PD-1+ e de células TIGIT+ em comparação com o controle. De relevância clínica, o inibidor A485 foi capaz de modular células CAR-T anti-CD19 isoladas de produtos de infusão, aumentando a frequência do marcador CD69 e modulando seu perfil fenotípico, menos diferenciado, em comparação ao controle. Além disso, o inibidor A485 potencializou a ação antitumoral das células CAR-T anti-CD19 em ensaios de co-cultura com a linhagem celular Daudi CD19+. Em resumo, os nossos dados mostram que a inibição de p300/CBP induz um perfil TN/TSCM em células T CD8 ativadas e em células CAR-T, potencializando as suas atividades antitumorais. Posto que a retenção do perfil TN/TSCM favorece o controle tumoral, esses achados podem ter implicações clínicas para pacientes com doenças hematológicas e com tumores sólidos.

CD8 T lymphocytes are key cells for the induction of antitumor responses. Once activated, these cells undergo epigenetic changes, acquire distinct phenotypes, and their function is linked to the production of cytotoxic and inflammatory mediators. However, these cells are dysfunctional within the tumor microenvironment. Therefore, strategies capable of reprogramming CD8 T cells can enhance their antitumor efficacy. Previous studies have shown that epigenetic inhibitors can modulate the profile of CD4 T cells, but the effects on CD8 T cells are still to be clarified. Thus, we aimed to identify possible epigenetic inhibitors that can modulate the activity and phenotype of CD8 T lymphocytes. To do this, CD8 T lymphocytes were isolated by cell sorting from healthy blood samples and cultured in 96-well plates in the presence of a polyclonal stimulatory cocktail (i.e., anti-CD3/CD28 DynaBeads, recombinant (r)IFN-, and rIL-2) along with 1µM of different epigenetic inhibitors (i.e., MS023, A485, LMOSES, GSKLSD1, and A366). Unstimulated CD8 T lymphocytes and polyclonally-stimulated CD8 T lymphocytes in the absence of epigenetic inhibitors were used as controls. After 4 or 8 days of culture, the cells were analyzed by flow cytometry for the assessment of cell markers related to activation (CD69), function (IFN- and granzyme B), differentiation (CCR7 and CD45RA) and exhaustion (PD-1 and TIGIT). Cells were acquired by the BD FACSymphony A5 cytometer, and statistical analyses were done using the GraphPad Prism 9 software. First, we conducted in vitro assays in which CD8 T cells were activated in the presence or absence of different inhibitors. A485, a p300/CBP bromodomain inhibitor, showed a potent modulatory effect on CD8 T cells. The inhibitor A485 increased T cell activation, observed by the increased frequency of CD69+ CD8 T cells. This inhibitor could also modulate the T cell memory phenotype, polarizing them towards a TN/TSCM profile, unlike the control and the other inhibitors, which polarized them towards to the TEM (effector memory T cells) profile. When the analyses were conducted after eight days of culture, we observed that the treatment with the A485 inhibitor resulted in a lower frequency of PD-1+ and TIGIT+ T cells compared with CD8 T cells activated in the absence of the inhibitor. Of clinical relevance, A485 was able to modulate anti-CD19 CAR-T cells isolated from pre-infusion products by positively regulating the frequency of CD69+ CAR-T cells and modulating their memory phenotype, keeping these cells less differentiated. In addition, A485 potentiated the in vitro antitumor activity of antiCD19 CAR-T cells in co-culture assays with the CD19+ Daudi cell line. In summary, our data show that the p300/CBP inhibition induces the TN/TSCM profile in CD8 T cells and CAR-T cells, thus boosting their antitumor activitiesSince the TN/TSCM phenotype has been shown to be favorable for tumor control, these findings can be of clinical interest for patients with hematological malignancies and solid tumors.

Adolescent mothers, self-care and childcare: content validation of an Event History Calendar / Madres adolescentes, autocuidado y cuidado de los hijos: validación del contenido de un calendario histórico de acontecimientos / Mães adolescentes, autocuidado e cuidado infantil: validação de conteúdo de um calendário histórico de eventos

ABSTRACT Objective: To validate the content of the tool Event History Calendar Adolescent Mother: strengthening self-care and child care. Method: Methodological study using the Delphi technique, conducted in two rounds, involving 37 nursing specialists. In data collection, from December/2019 to August/2020, a semi-structured questionnaire composed of 47 items related to the two dimensions of the tool: Self-care and Child Care was used. The Content Validity Index ≥ 0.80 was used to assess agreement among the experts. Qualitative elements were analyzed for clarity and comprehensiveness of content. Results: In the first round, 46 items showed Content Validity Index ≥ 0.80. The qualitative elements pointed out more clarity for the adolescent audience. After the changes, the tool presented 30 items. In the second round, the 30 items evaluated achieved Content Validity Index ≥ 0.80. The qualitative considerations were translated into modifications in the content and sequence in the final version of the tool. Conclusion: The validated tool obtained adequate evaluation of the items of each dimension, related to adolescent mother self-care and child care, with a high degree of comprehensibility.

RESUMEN Objetivo: Validar el contenido de la herramienta Event History Calendar Madre Adolescente: fortaleciendo el autocuidado y el cuidado de los hijos. Método: Estudio metodológico mediante la técnica Delphi, realizado en dos rondas, en el que participaron 37 expertos en enfermería. En la recopilación de datos, de diciembre de 2019 a agosto de 2020, se utilizó un cuestionario semiestructurado compuesto por 47 ítems relacionados con dos dimensiones de la herramienta: Autocuidado y Cuidado del niño. Se utilizó el Índice de Validez del Contenido ≥ 0,80 para evaluar el acuerdo entre los expertos. Se analizaron los elementos cualitativos para comprobar la claridad y exhaustividad del contenido. Resultados: En la primera ronda, 46 ítems presentaron Índice de Validez de Contenido ≥ 0,80. Los elementos cualitativos apuntan a la necesidad de una mayor claridad para el público adolescente. Tras los cambios, la herramienta presentaba 30 ítems. En la segunda ronda, los 30 ítems evaluados alcanzaron un Índice de Validez de Contenido ≥ 0,80. Las consideraciones cualitativas se tradujeron en modificaciones del contenido y la secuencia en la versión final de la herramienta. Conclusión: El instrumento validado obtuvo evaluación adecuada de los ítems de cada dimensión, relacionados al autocuidado de la madre adolescente y al cuidado del niño, con alto grado de comprensibilidad.

RESUMO Objetivo: Validar o conteúdo da ferramenta Event History Calendar Mãe Adolescente: fortalecendo o autocuidado e o cuidado da criança. Método: Estudo metodológico com a técnica Delphi, realizado em duas rodadas, envolvendo 37 especialistas de enfermagem. Na coleta de dados, de dezembro/2019 a agosto/2020, foi utilizado um questionário semiestruturado composto por 47 itens relacionados às duas dimensões da ferramenta: Autocuidado e Cuidado da criança. O Índice de Validade de Conteúdo ≥ 0,80 foi utilizado para avaliar a concordância entre os especialistas. Elementos qualitativos foram analisados quanto à clareza e abrangência do conteúdo. Resultados: Na primeira rodada, 46 itens apresentaram Índice de Validade de Conteúdo ≥ 0,80. Os elementos qualitativos apontaram necessidade de maior clareza para o público adolescente. Após as alterações, a ferramenta apresentou 30 itens. Na segunda rodada, os 30 itens avaliados alcançaram Índice de Validade de Conteúdo ≥ 0,80. As considerações qualitativas foram traduzidas em modificações no conteúdo e sequência na versão final da ferramenta. Conclusão: A ferramenta validada obteve avaliação adequada dos itens de cada dimensão, relacionados ao autocuidado da mãe adolescente e cuidado da criança, com alto grau de compreensibilidade.

Research Progress of Chimeric Antigen Receptor Modified NK Cells in the Treatment of Acute Myeloid Leukemia --Review / 中国实验血液学杂志

Chimeric Antigen Receptor (CAR) is a research hotspot in the field of cellular immunotherapy in recent years, and CAR-T cells therapy are developing rapidly in hematological malignant tumors, but their clinical application is still limited by related risks. It is particularly important to find more optimized immunoreactive cells. Natural killer (NK) cells, as key effector cells of innate immunity, can kill tumor or infected cells quickly without prior sensitization. Autologous or allogeneic NK cell infusion has become an effective cell therapy for acute myeloid leukemia (AML). CAR-NK cells combine the advantages of CAR targeting tumor specific antigens and enhancing immune cells activity with the innate antitumor function of NK cells to enhance the targeting and lytic activity of NK cells to AML primordial cells. At present, most of the CAR-NK treatments for AML are still in the stage of specific target screening and verification. This article reviews the latest research progress of CAR-NK cell therapy in the field of AML therapy.

Progress in Research and Application of CAR-T Cell Therapy in T-Lymphocyte Tumors --Review / 中国实验血液学杂志

T-lymphocyte tumors are a group of diseases containing various types of lymphatic system tumors, with strong heterogeneity and poor clinical outcomes. Chimeric antigen receptor T (CAR-T) cell therapy, as a new immune cell therapy, has made a breakthrough in the field of B-lymphocyte tumors. People are interested in the application prospect of this technique in the field of T-lymphocyte tumors. Some studies have shown that CAR-T cell therapy has made some progress in the treatment of T-lymphocyte tumors, and CAR-T for some targets has entered the stage of clinical trials. However, due to the characteristics of T cells, there are also many challenges. This article reviews the research and application of CAR-T cell therapy in T-lymphocyte tumors.

Universal chimeric Fcγ receptor T cells with appropriate affinity for IgG1 antibody exhibit optimal antitumor efficacy

Developing universal CARs with improved flexible targeting and controllable activities is urgently needed. While several studies have suggested the potential of CD16a in tandem with monoclonal antibodies to construct universal CAR-T cells, the weak affinity between them is one of the limiting factors for efficacy. Herein, we systematically investigated the impact of Fcγ receptor (FcγR) affinity on CAR-T cells properties by constructing universal CARs using Fcγ receptors with different affinities for IgG1 antibodies, namely CD16a, CD32a, and CD64. We demonstrated that the activities of these universal CAR-T cells on tumor cells could be redirected and regulated by IgG1 antibodies. In xenografted mice, 64CAR chimeric Jurkat cells with the highest affinity showed significant antitumor effects in combination with herceptin in the HER2 low expression U251 MG model. However, in the CD20 high expression Raji model, 64CAR caused excessive activation of CAR-T cells, which resulted in cytokine release syndrome (CRS) and the decline of antitumor activity, and 32CAR with a moderate affinity brought the best efficacy. Our work extended the knowledge about FcγR-based universal CAR-T cells and suggested that only the FcγRCAR with an appropriate affinity can offer the optimal antitumor advantages of CAR-T cells.

Development strategy and clinical research progress of universal chimeric antigen receptor T-cell drugs / 中国药科大学学报

@#Chimeric antigen receptor T-cell (CAR-T) immunotherapy has made a breakthrough in the clinical treatment of a variety of hematological tumors.However, the CAR-T cell products listed at China and abroad are all autologous CAR-T.Compared with autologous CAR-T treatment, universal CAR-T exhibits significant advantages, which could fulfill the treatment demand of more patients, but also displays high technical barriers.This paper reviews the universal CAR-T, clearly points out the two major challenges faced by the development of universal CAR-T, and then summarizes and analyzes the feasible solutions according to the mechanism causing the two major problems.This paper also summarizes domestic and foreign companies producing universal CAR-T and the latest clinical progress of their superior products, and then discusses the feasibility of the development strategy from another aspect, in order to provide ideas for developing a new generation of universal CAR-T cell therapy products.

Genome editing in cancer biotherapy: strategies, challenges and future directions / 中国肿瘤生物治疗杂志

@#[摘 要] CRISPR等基因编辑技术在多学科、多领域产生了革命性影响，也极大地推动了肿瘤生物治疗研究方法的转变和治疗新策略的形成。在肿瘤研究中，基因编辑加速了肿瘤细胞和免疫细胞中生物治疗新靶点的发现，推动了癌基因、抑癌基因、表观分子、耐药基因等“肿瘤细胞正常化”靶向编辑新策略的提出，促进了CAR-T、TCR-T细胞等过继细胞治疗方法向“通用型”、“即用型”的迭代，也极大地加速了CAR-T细胞等细胞治疗的临床应用。通过更加精准基因编辑系统的研发、基因递送策略的不断进步，以及多靶点编辑、定点插入和体内时空可控编辑的发展，将进一步降低基因编辑的脱靶效应，提高疗效和安全性，同时控制成本，推动基因编辑在肿瘤生物治疗中更加广泛的应用，且有望在实体瘤治疗方面实现新的突破。

Establishment and observation of a mouse model of IL-12-CAR-T cell-induced cytokine release syndrome / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：通过构建表达IL-12的小鼠CAR-T细胞，探讨经尾静脉将其输注于小鼠体内建立细胞因子释放综合征（CRS）模型的方法。方法：构建基于靶向鼠源CD19的CAR分子，包装逆转录病毒载体并感染小鼠T细胞构建mCD19-CAR-T、mCD19/IL-12-CAR-T细胞。通过构建小鼠体内胰腺癌Panc02-CD19细胞移植瘤模型，检测mCD19/IL-12-CAR-T细胞的抗肿瘤活性，ELISA法检测两种CAR-T细胞IL-12和IFN-γ分泌水平；经小鼠尾静脉输注mCD19/IL-12-CAR-T 细胞构建CAR-T细胞CRS小鼠模型，流式细胞术检测小鼠血清中IL-6、MCP-1、IL-1、IL-10、TNF-α、IFN-γ等细胞因子的含量，H-E染色法观察荷瘤小鼠肝、脾、肺和肾的病理组织学变化。结果：经过培养扩增的mCD19/IL-12-CAR-T细胞能有效分泌IL-12，CAR阳性率达（56.9±5.4）%；与非靶细胞Panc02或靶细胞Panc02-CD19共培养时，均能高分泌IFN-γ。成功构建小鼠胰腺癌Panc02-CD19细胞移植瘤模型，经小鼠尾静脉注射1×106个mCD19/IL-12-CAR-T细胞能显著抑制移植瘤的生长，但未能诱发严重CRS；输注2×106个mCD19/IL-12-CAR-T细胞后，小鼠出现体质量减轻、血清炎性因子水平升高、组织损伤，最终导致死亡等一系列典型CRS表现。结论：成功构建IL-12-CAR-T细胞诱发的小鼠CRS模型，其稳定性好、重复性高，具有广泛的应用前景。

Research progress of CAR-T immunotherapy in solid tumors combined with new strategies / 中国药科大学学报

@#In recent years, the chimeric antigen receptor T-cell (CAR-T) therapy has achieved breakthrough progress in the treatment of hematologic malignancies. However, when it comes to solid tumors, numerous challenges persist.These include limited CAR-T cell infiltration, susceptibility to T cell exhaustion, off-target effects, and more.Thus, novel therapeutic strategies are imperative to enhance the efficacy of CAR-T therapy for solid tumors. In comparison to standalone CAR-T approaches, the combination of CAR-T with other tumor treatment modalities has demonstrated remarkable effectiveness in both preclinical and clinical research.This review article summarizes the advancements in combining CAR-T with various solid tumor treatments: antibody drugs, oncolytic viruses, tumor vaccines, and nanomedicines.The objective is to furnish a theoretical foundation and novel perspectives for the development of innovative CAR-T combination strategies tailored for solid tumor therapy.

Advances in application of regulatory T cells in transplant immune tolerance: from basic to clinical research / 器官移植

Regulatory T cells (Treg) are important inhibitory immune cells to establish immune tolerance, which play a pivotal role in regulating excessive immune response and autoimmune diseases of the host. Previous studies related to transplant immune tolerance have confirmed that increasing the number of Treg in vivo or enhancing the function of Treg serve as a therapeutic strategy to induce transplant immune tolerance. At present, Treg-based induction methods for transplant immune tolerance include adoptive infusion of Treg, in vivo amplification of Treg and utilization of antigen-specific Treg. In this article, the characteristics and mechanism of Treg, the latest research progress on basic experiments and clinical practice of Treg related to transplant immune tolerance at home and abroad were reviewed, and future challenges and development of Treg therapy were prospected, aiming to unravel the significance and application prospect of Treg in transplant immune tolerance, explore the advantages and limitations of Treg therapeutic strategies, and provide reference and evidence for subsequent research in this field.

Advances in Emerging Therapies for Multiple Myeloma / 肿瘤防治研究

Multiple myeloma (MM) is an incurable plasma cell malignancy with a typical course characterized by response to initial treatment and eventual resistance. Despite major advances in the clinical treatment of multiple myeloma driven by the introduction of new drugs (e.g., proteasome inhibitors and immunomodulators), MM remains incurable. Nevertheless, subsequent cycles of remission and relapse continue as long as new treatments are available to patients. With the development of many new treatments, the approval of 12 new drugs over the past 15 years, and the promising trend of clinical trials, the treatment landscape has dramatically changed and patient survival has improved. This article reviews the progress of new treatments for MM.

CAR-T cell therapy for multiple myeloma: a practical toolkit for treatment in Brazil

ABSTRACT Introduction Chimeric antigen receptor T (CAR-T) cell therapy is an emerging treatment option for relapsed/refractory multiple myeloma (RRMM) that is a multi-step process involving various stakeholders. Appropriate education on the practical logistics is therefore paramount to ensure treatment success. Methods A group of key opinion leaders met to explore the key elements of setting up and running a CAR-T center in Brazil. For each step in the CAR-T cell therapy process, the experts agreed on basic requirements, gave their key recommendations from practical experience, and considered any remaining unanswered questions. Results This paper presents best-practice recommendations and advice on how to overcome common challenges for each step in the CAR-T cell therapy process, with a focus on the current situation in Brazil. Key themes throughout the process are collaboration within the multidisciplinary team and with the referring physician, along with communication and education for patients and their caregivers. Conclusion We believe that the expert insights presented in this paper, in particular on optimal patient selection and timing of CAR-T cell therapy, will deepen understanding of the CAR-T process and aid implementation of this novel therapy for patients with RRMM in Brazil.