Prevalência de tabagismo e morbimortalidade por câncer de pulmão nos estados brasileiros / Smoking prevalence and lung cancer morbimortality in Brazilian states / Prevalencia del tabaquismo y morbimortalidad por cáncer de pulmón en los estados brasileños

Introdução: O câncer de pulmão é uma doença grave, sendo a segunda maior causa de morte em todo o mundo, entretanto, em alguns países desenvolvidos, tornou-se já a primeira causa de morte. Cerca de 90% dos casos de neoplasia pulmonares são causados pela inalação da fumaça do cigarro. Objetivo: Correlacionar a prevalência de tabagismo e morbimortalidade por câncer de pulmão nos estados brasileiros, além de demonstrar a associação destes com sexo e faixa etária. Métodos: Estudo de caráter ecológico acerca da prevalência de tabagismo e morbimortalidade por câncer de pulmão nos estados brasileiros, nos períodos de 2013 e 2019, dividida por sexo e faixa etária. Foram utilizados bancos de coleta de dados como o Tabnet e Pesquisa Nacional de Saúde. Resultados: As maiores taxas de mortalidade e internações hospitalares foram do público masculino, em 2013, com taxa de 2,7 e 10, respectivamente, e em 2019 com 3,3 e 11,9, respectivamente. Ademais, a maior prevalência de tabagismo foi encontrada nos homens; entretanto seu índice tem caído, enquanto a quantidade de mulheres tabagistas tem aumentado. A Região Sul demonstrou maiores números de mortalidade em ambos os períodos estudados, com taxas de 4,9 e 5,8 por 100 mil habitantes, e morbidade hospitalar com 19,9 e 23,5 por 100 mil habitantes. Já a Região Norte se configurou com as menores prevalências: em 2013 apresentou taxa de óbito por câncer de pulmão de 1,0 e morbidade hospitalar de 3,5/100 mil habitantes, em 2019 apresentou taxa de mortalidade de 4,6 e internações de 1,6/100 mil habitantes. Os coeficientes de correlação de morbidade hospitalar e prevalência de tabagismo foram R2=0,0628, r=0,251 e p=0,042, enquanto os de mortalidade e prevalência de tabagismo foram R2=0,0337, r=0,183 e p=0,140. Conclusões: Na presente pesquisa, pode-se inferir que houve associação positiva na comparação entre taxa de morbidade hospitalar e prevalência de tabagismo; em contrapartida, não foi possível observar associação positiva na correlação da taxa de mortalidade por câncer de pulmão e prevalência de tabagismo.

Introduction: Lung cancer is a serious disease, being the second leading cause of death worldwide. Moreover, in some developed countries, it has already become the leading cause of death. About 90% of lung cancer cases are caused by cigarette smoking. Objective: To correlate the prevalence of smoking and lung cancer morbidity and mortality in Brazilian states, and to demonstrate their association with sex and age group as well. Methods: An ecological study on the prevalence of smoking and lung cancer morbidity and mortality in Brazilian states between 2013 and 2019, divided by sex and age group. The data collection databases Tabnet and National Health Survey were used. Results: The highest rates of mortality and hospital admissions were among men, in 2013 with a rate of 2.7 and 10, respectively, and in 2019 with 3.3 and 11.9, respectively. In addition, the highest prevalence of smoking was found in men, but this rate has fallen, while the number of women smokers has increased. The South region showed higher mortality rates in both periods studied, with rates of 4.9 and 5.8 per 100,000 inhabitants, and hospital morbidity with 19.9 and 23.5 per 100,000 inhabitants. The North region had the lowest prevalence, where in 2013, it had a death rate from lung cancer of 1.0 and hospital morbidity of 3.5/100 thousand inhabitants, and where in 2019, it had a mortality rate of 4.6 and hospitalizations of 1.6/100 thousand inhabitants. The correlation coefficients for hospital morbidity and smoking prevalence were R2=0.0628, r=0.251 and p=0.042, while for mortality and smoking prevalence, these were R2=0.0337, r=0.183 and p=0.140. Conclusions: In the present study, it can be inferred that there was a positive association between hospital morbidity rate and prevalence of smoking, while it was not possible to observe a correlation between lung cancer mortality rate and prevalence of smoking.

Introducción: El cáncer de pulmón es una enfermedad grave, siendo la segunda causa de muerte en todo el mundo, sin embargo, en algunos países desarrollados, ya se ha convertido en la primera causa de muerte. Alrededor del 90% de los casos de neoplasias pulmonares están causados por la inhalación del humo del cigarrillo. Objetivo: Correlacionar la prevalencia de tabaquismo y la morbimortalidad por cáncer de pulmón en los estados brasileños, además de demostrar la asociación de estos con el género y el grupo de edad. Métodos: estudio ecológico sobre la prevalencia de tabaquismo y morbimortalidad por cáncer de pulmón en los estados brasileños, dentro de los períodos 2013 y 2019, divididos por sexo y grupo de edad. Se utilizaron bancos de recogida de datos como Tabnet y la Encuesta Nacional de Salud. Resultados: las mayores tasas de mortalidad e ingresos hospitalarios se dieron en el público masculino, en 2013 con una tasa de 2,7 y 10, respectivamente, y en 2019 con 3,3 y 11,9, respectivamente. Además, la mayor prevalencia del tabaquismo se encontró en los hombres, sin embargo, su tasa ha disminuido, mientras que la cantidad de mujeres fumadoras ha aumentado. La región Sur presentó cifras más altas de mortalidad en ambos periodos estudiados, con tasas de 4,9 y 5,8 por 100.000 habitantes, y de morbilidad hospitalaria con 19,9 y 23,5 por 100.000 habitantes. Mientras que la región Norte se configuró con las prevalencias más bajas, en 2013 presentó una tasa de mortalidad por cáncer de pulmón de 1,0 y una morbilidad hospitalaria de 3,5/100.000 habitantes, en 2019 presentó una tasa de mortalidad de 4,6 y hospitalizaciones de 1,6/100.000 habitantes. Los coeficientes de correlación para la morbilidad hospitalaria y la prevalencia del tabaquismo fueron R2=0,0628, r=0,251 y p=0,042, mientras que para la mortalidad y la prevalencia del tabaquismo fueron R2=0,0337, r=0,183 y p=0,140. Conclusiones: En la presente investigación se puede inferir que existe una asociación positiva en la comparación entre la tasa de morbilidad hospitalaria y la prevalencia de tabagismo, en contrapartida, no fue posible observar una asociación positiva en la correlación de la tasa de mortalidad por cáncer de pulmón y la prevalencia de tabagismo.

Hallazgos imagenológicos torácicos en seguimiento de pacientes con síndrome PostCovid-19 / Thoracic imagenological findings in follow-up of patients with Post-Covid-19 syndrome

Objetivo: Describir los hallazgos imagenológicos en radiografías de tórax y ecografías pulmonares de pacientes con síndrome post-COVID-19. Métodos: estudio descriptivo, prospectivo y transversal que incluyó pacientes con síndrome post-COVID-19, sometidos a radiografías de tórax y ecografías pulmonares en el Servicio de Neumonología Clínica del Hospital Dr. José Ignacio Baldo, entre enero y octubre de 2022, con la finalidad de establecer su evolución imagenológica pulmonar. Se utilizó estadística descriptiva, chi-cuadrado de Pearson y prueba kappa de concordancia, considerando significativo un valor de p < 0,05. Resultados: La muestra consistió en 58 pacientes con una edad media de 55 ± 13 años, predominando el sexo femenino (58,6%). El 60,3% mostró alteraciones en la radiografía de tórax; un 74,3% con patrón intersticial bilateral y un 25,7% con patrón intersticial unilateral. La ecografía reveló patrón intersticial en el 43,1% de los casos y se observaron dos microconsolidaciones subpleurales. Conclusiones: Las radiografías de tórax y las ecografías pulmonares son herramientas imagenológicas eficaces, accesibles y económicas para detectar alteraciones en pacientes con síndrome post-COVID-19. (AU)

Objective: To describe imaging findings in chest radiographs and lung ultrasounds of patients with post-COVID-19 syndrome. Methods: A descriptive, prospective, and cross-sectional study was carried out that included patients with post-COVID-19 syndrome, who underwent chest radiographs and lung ultrasounds at the Clinical Pneumonology Service of Dr. José Ignacio Baldo Hospital, between January and October 2022. Descriptive statistics, Pearson's chi-square, and kappa concordance test were used, considering a p-value < 0.05 significant. Results: The sample consisted of 58 patients with an average age of 55 ± 13 years, with a predominance of females (58.6%). 60.3% showed alterations in the chest radiograph; 74.3% with a bilateral interstitial pattern and 25.7% with a unilateral interstitial pattern. The ultrasound revealed an interstitial pattern in 43.1% of the cases and two subpleural microconsolidations were observed. Conclusions: Chest radiographs and lung ultrasounds are effective, accessible, and economical imaging tools to detect alterations in patients with post-COVID-19 syndrome. (AU)

Presentación inusual de coriocarcinoma metastásico a hígado y pulmón: un reporte de caso / Unusual presentation of metastatic choriocarcinoma to liver and lung: a case report

La enfermedad trofoblástica gestacional (ETG) es un trastorno proliferativo del trofoblasto. Incluye la mola hidatidiforme, el coriocarcinoma, la mola invasiva, el tumor trofoblástico del lecho placentario y el tumor trofoblástico epitelioide. Las últimas cuatro hacen parte de la neoplasia trofoblástica gestacional, que agrupa menos del 1% de todos los tumores ginecológicos. La incidencia de la ETG puede variar, siendo aproximadamente de 1 a 3 de cada 1.000 embarazos en América del Norte y Europa. El coriocarcinoma es la forma más agresiva por su rápida invasión vascular y compromiso metastásico. Sin embargo, es un tumor muy quimiosensible con una alta tasa de respuestas y posibilidad de curación superior al 90%. Se presenta el caso de una paciente de 40 años quien ingresó al servicio de urgencias por disnea súbita secundaria a tromboembolia pulmonar y posteriormente tras el inicio de anticoagulación presentó hemoperitoneo debido a lesiones hepáticas metastásicas de un coriocarcinoma, además de compromiso metastásico pulmonar. Se presenta este caso por ser una patología poco frecuente, agresiva y con presentaciones inusuales, con el fin de mostrar la importancia de un diagnóstico y tratamiento oportuno.

Gestational trophoblastic disease (GTD) is a condition in which the trophoblast, a layer of cells surrounding the embryo, develops abnormally. GTD includes both pre-malignant and malignant pathologies, such as hydatidiform mole, choriocarcinoma, invasive mole, placental site trophoblastic tumor, and epithelioid trophoblastic tumor. Although GTD is rare, it affects about 1 to 3 out of every 1,000 pregnancies in North America and Europe. Choriocarcinoma is the most aggressive form of GTD, as it can quickly invade blood vessels and metastasize to other parts of the body. However, it is highly responsive to chemotherapy, with a cure rate of over 90%. In this case, a 40-year-old patient presented to the emergency department with sudden dyspnea due to pulmonary embolism. After starting anticoagulation therapy, she developed hemoperitoneum due to the spread of choriocarcinoma to her liver, as well as pulmonary metastases. This case is noteworthy because of its unusual presentation and aggressive nature, underscoring the importance of early diagnosis and treatment.

Fotocoagulación láser guiada por ultrasonido para el tratamiento del secuestro broncopulmonar fetal. Reporte de dos casos exitosos en Venezuela / Ultrasound-guided laser photocoagulation for the treatment of fetal bronchopulmonary sequestration. Report of two successful cases in Venezuela

El secuestro broncopulmonar es una malformación del aparato respiratorio que consiste en tejido bronquial y pulmonar no funcionante, separado del árbol tráqueo-bronquial y alimentado por un vaso sanguíneo proveniente de la circulación sistémica. La incidencia es de 1 por cada 5000 nacimientos, comprende entre 0,15 % y 6,45 % de las patologías pulmonares. El pronóstico es, generalmente, favorable, reportándose regresión espontánea de la lesión en 50 % a 75 % de los pacientes. Puede ocasionar efecto de masa, comprimiendo el corazón y el pulmón hasta generar cambios hemodinámicos y falla cardíaca. Hay múltiples procedimientos para el tratamiento y manejo, principalmente en casos de gran tamaño y fetos hidrópicos, para mejorar el pronóstico perinatal. Se presentan los dos primeros casos de secuestro broncopulmonar tratados en Venezuela mediante fotocoagulación láser del vaso nutricio y su evolución perinatal, con sobrevida del 100 % y sin ninguna complicación registrada en el periodo perinatal(AU)

Bronchopulmonary sequestration is a malformation of the respiratory system consisting of non-functioning bronchial and pulmonary tissue, separated from the tracheo-bronchial tree and fed by a blood vessel from the systemic circulation. The incidence is 1 in 5000 births, ranging from 0.15% to 6.45% of pulmonary pathologies. The prognosis is generally favorable, with spontaneous regression of the lesion reported in 50% to 75% of patients. It can cause mass effect, compressing the heart and lung to the point of generating hemodynamic changes and heart failure. There are multiple procedures for treatment and management, mainly in large cases and hydropic fetuses, to improve perinatal prognosis. We present the first two cases of bronchopulmonary sequestration treated in Venezuela by laser photocoagulation of the nutrient vessel and their perinatal evolution, with 100% survival and without any complications recorded in the perinatal period(AU)

Controles de salud durante la pandemia e impacto clínico del COVID-19 en niños con enfermedad neuromuscular / Health checkups during the pandemic and clinical impact of COVID-19 in children with neuromuscular disease

Introducción. Los niños con enfermedad neuromuscular (ENM) requieren cuidados crónicos de salud (CCS) y podrían presentar COVID-19 grave. Objetivos. Describir CCS para niños con ENM durante la pandemia y evolución del COVID-19 en este grupo. Población y métodos. Cohorte prospectiva unicéntrica. Se incluyeron pacientes de 2-18 años, con ≥ 1 año de seguimiento previo a la pandemia. Se recolectaron variables demográficas, relativas a los CCS y al COVID-19 mediante historias clínicas y encuestas telefónicas. Resultados. Se incluyeron 226 pacientes; el 71 % varones, mediana de edad 11,3 años. Presentaban distrofias musculares (55,7 %) y atrofia muscular espinal (23 %). Comparando el primer año de pandemia con el previo, el 30 % no realizó controles médicos y el 25 % no realizó kinesioterapia. Otros disminuyeron la frecuencia. Hubo 52 casos de COVID-19. Fueron sintomáticos el 82 %: el 88,4 % leves/moderados y el 11,6 % graves. No hubo fallecidos. Conclusiones. La pandemia impactó negativamente en los CCS y los casos de COVID-19 fueron mayormente leves.

Introduction. Children with neuromuscular disease (NMD) require chronic health care (CHC) and may develop severe COVID-19. Objectives. To describe CHC for children with NMD during the pandemic and the course of COVID-19 in this group. Population and methods. Prospective, single-center cohort. Patients aged 2 to 18 years with ≥ 1 year of follow-up prior to the pandemic were included. Demographic variables in relation to CHC and COVID-19 were collected from medical records and via telephone surveys. Results. A total of 226 patients with a median age of 11.3 years were included; 71% were males. They had muscular dystrophy (55.7%) and spinal muscular atrophy (23%). When comparing the first year of the pandemic with the previous year, 30% did not have a health checkup and 25% did not receive kinesiotherapy. Others did, but with a lower frequency. A total of 52 COVID-19 cases were reported; 82% were symptomatic: 88.4% were mild/moderate and 11.6%, severe. No patient died. Conclusions. The pandemic had a negative impact on CHC, and COVID-19 cases were mostly mild.

Disfunciones del metabolismo del surfactante pulmonar: caso clínico pediátrico / Pulmonary surfactant metabolism dysfunction: A pediatric clinical case report

Las enfermedades pulmonares intersticiales son patologías poco frecuentes en pediatría. Dentro de ellas, se incluyen las disfunciones del metabolismo del surfactante pulmonar, molécula anfipática cuya función es disminuir la tensión superficial y evitar el colapso alveolar. Se presenta el caso de un lactante de 6 meses, en seguimiento por bajo peso, que presentó dificultad respiratoria aguda y cianosis; la radiografía de tórax evidenció infiltrado intersticial, neumomediastino y neumotórax bilateral. Al interrogatorio, surgió antecedente materno de internación al año de vida, con requerimiento de oxigenoterapia prolongada y diagnóstico desconocido; presenta signos de hipoxia crónica. El paciente cursó internación con requerimiento de oxigenoterapia. Se realizaron estudios complementarios en búsqueda de etiología, sin resultados positivos. La tomografía de tórax evidenció opacidades en vidrio esmerilado, engrosamiento del intersticio septal y áreas de atrapamiento aéreo; con resultado de biopsia pulmonar y estudio genético se llegó al diagnóstico de disfunción del metabolismo del surfactante pulmonar.

Interstitial lung diseases are rare in pediatrics. They include dysfunctions in the metabolism of pulmonary surfactant, an amphipathic molecule that reduces surface tension and prevents alveolar collapse. Here we describe the case of a 6-month-old infant controlled for low weight, who presented with acute respiratory distress and cyanosis; his chest X-ray showed interstitial infiltrate, pneumomediastinum, and bilateral pneumothorax. During history-taking, it was noted that his mother had a history of hospitalization at 1 year old with unknown diagnosis, requiring prolonged oxygen therapy; she now shows signs of chronic hypoxia. The patient was hospitalized and required oxygen therapy. Ancillary tests were done to look for the etiology of the condition, with no positive results. A chest computed tomography showed groundglass opacities, thickening of the septal interstitium, and areas of air trapping; based on the results of a lung biopsy and a genetic study, pulmonary surfactant metabolism dysfunction was diagnosed.

Retos y avances del cáncer de pulmón de células no pequeñas metastásico EGFR mutado / Challenges and advances in metastatic non-small cell lung cancer with EGFR mutation

RESUMEN Los inhibidores de la tirosina quinasa han cambiado drásticamente la perspectiva clínica de los pacientes con cáncer de pulmón de células no pequeñas avanzado con mutaciones del receptor del factor de crecimiento epidérmico. Sin embargo, existen aún retos en el manejo de los pacientes con esta mutación en un escenario metastásico, como es la resistencia intrínseca y adquirida a inhibidores de tirosina quinasa. Se discutirán los últimos avances y nuevas estrategias en primera línea de tratamiento, resistencia a osimertinib y tratamiento en mutación, en el exón 20.

ABSTRACT Tyrosine kinase inhibitors have dramatically changed the clinical outcomes for patients with advanced non-small cell lung cancer with epidermal growth factor receptor mutations. However, there are still challenges in the management of patients with this mutation in a metastatic setting, such as intrinsic and acquired resistance to tyrosine kinase inhibitors. We will discuss the latest advances and new strategies in first-line treatment, osimertinib resistance, and exon 20 mutation treatment.

Prediction of Prognostic Features Based on Neutrophil-Related Genes for Lung Squamous Cell Carcinoma Reveals Immune Landscape and Drug Candidates

ABSTRACT Background: Since to the prognosis of lung squamous cell carcinoma is generally poor, there is an urgent need to innovate new prognostic biomarkers and therapeutic targets to improve patient outcomes. Objectives: Our goal was to develop a novel multi-gene prognostic model linked to neutrophils for predicting lung squamous cell carcinoma prognosis. Methods: We utilized messenger RNA expression profiles and relevant clinical data of lung squamous cell carcinoma patients from the Cancer Genome Atlas database. Through K-means clustering, least absolute shrinkage and selection operator regression, and univariate/multivariate Cox regression analyses, we identified 12 neutrophil-related genes strongly related to patient survival and constructed a prognostic model. We verified the stability of the model in the Cancer Genome Atlas database and gene expression omnibus validation set, demonstrating the robust predictive performance of the model. Results: Immunoinfiltration analysis revealed remarkably elevated levels of infiltration for natural killer cells resting and monocytes in the high-risk group compared to the low-risk group, while macrophages had considerably lower infiltration in the high risk group. Most immune checkpoint genes, including programmed cell death protein 1 and cytotoxic T-lymphocyte-associated antigen 4, exhibited high expression levels in the high risk group. Tumor immune dysfunction and exclusion scores and immunophenoscore results suggested a potential inclination toward immunotherapy in the "RIC" version V2 revised high risk group. Moreover, prediction results from the CellMiner database revealed great correlations between drug sensitivity (e.g., Vinorelbine and PKI-587) and prognostic genes. Conclusion: Overall, our study established a reliable prognostic risk model that possessed significant value in predicting the overall survival of lung squamous cell carcinoma patients and may guide personalized treatment strategies. (Rev Invest Clin. 2024;76(2):116-31)

Hipertensão Arterial Pulmonar com Características de Envolvimento Venoso: Um Trabalho Investigativo / Pulmonary Arterial Hypertension with Features of Venous Involvement: A Detective's Task

Resumo A doença veno-oclusiva pulmonar (DVOP) e a hemangiomatose capilar pulmonar são tipos raros de substratos histopatológicos dentro do espectro da hipertensão arterial pulmonar (HAP) com prognóstico muito ruim. Caracterizam-se por um processo fibroproliferativo generalizado das veias e/ou capilares de pequeno calibre com preservação das veias maiores, resultando em um fenótipo de hipertensão pulmonar pré-capilar. A apresentação clínica é inespecífica e semelhante a outras etiologias de HAP. O diagnóstico definitivo é obtido por meio de análise histológica, embora a biópsia pulmonar não seja aconselhada devido ao maior risco de complicações. No entanto, alguns achados adicionais podem permitir um diagnóstico clínico presuntivo de DVOP, especialmente história de tabagismo, uso de drogas quimioterápicas, exposição a solventes orgânicos (particularmente tricloroetileno), baixa capacidade de difusão do monóxido de carbono (DLCO), dessaturação ao esforço e evidências de doença venosa sem doença cardíaca esquerda no exame de imagem, manifestada por uma tríade clássica de opacidades em vidro fosco, linhas septais, e linfadenopatias. O transplante pulmonar é o único tratamento eficaz e os pacientes devem ser encaminhados no momento do diagnóstico, devido à rápida progressão da doença e ao prognóstico ruim. Apresentamos o caso de um homem de 58 anos com HAP com características de envolvimento venoso/capilar em que a suspeita clínica, o pronto diagnóstico e o encaminhamento precoce para transplante pulmonar foram determinantes para um bom desfecho.

Abstract Pulmonary veno-occlusive disease (PVOD) and pulmonary capillary hemangiomatosis are rare types of histopathological substrates within the spectrum of pulmonary arterial hypertension (PAH) with a very poor prognosis. They are characterized by a widespread fibroproliferative process of the small caliber veins and/or capillaries with sparing of the larger veins, resulting in a pre-capillary pulmonary hypertension phenotype. Clinical presentation is unspecific and similar to other PAH etiologies. Definitive diagnosis is obtained through histological analysis, although lung biopsy is not advised due to a higher risk of complications. However, some additional findings may allow a presumptive clinical diagnosis of PVOD, particularly a history of smoking, chemotherapy drug use, exposure to organic solvents (particularly trichloroethylene), low diffusing capacity for carbon monoxide (DLCO), exercise induced desaturation, and evidence of venous congestion without left heart disease on imaging, manifested by a classical triad of ground glass opacities, septal lines, and lymphadenopathies. Lung transplant is the only effective treatment, and patients should be referred at the time of diagnosis due to the rapid progression of the disease and associated poor prognosis. We present a case of a 58-year-old man with PAH with features of venous/capillary involvement in which clinical suspicion, prompt diagnosis, and early referral for lung transplantation were determinant factors for the successful outcome.

Propuesta de estrategias terapéuticas combinadas para KRAS en cáncer de pulmón de células no pequeñas a partir de análisis in silico / Proposal of combined therapeutic strategies for KRAS in non-small cell lung cancer based on an in silico analysis

RESUMEN Objetivo: Los pacientes con cáncer de pulmón de células no pequeñas positivas a la mutación del gen linfoma anaplásico quinasa (ALK+) que, además, presentan mutaciones en el gen Kirsten rat sarcoma (KRAS), como KRASG12C, están mostrando resistencia tanto a inhibidores del gen linfoma anaplásico quinasa (ALK) como de KRAS. Por ello, se analizó la interacción de los inhibidores de ALK con KRAS, para sugerir una sinergia entre ambos. Materiales y métodos: En el estudio se realizó un modelado por homología de las estructuras KRASwt, KRASG12C y ALKwt. Posteriormente, se realizaron acoplamientos moleculares para determinar la energía de unión de los inhibidores de ALK y de KRAS, y evaluar la posible interacción entre los inhibidores de ALK con KRAS y la estructura KRASG12C. Finalmente, se analizó la expresión en la vía de proliferación celular de las proteínas rat sarcoma/quinasa regulada por señales extracelulares (vía RAS/MEK) mediante la técnica de Western blot. Resultados: Los valores de energía de unión muestran la posibilidad de interacción de los inhibidores de ALKwt, como crizotinib y alectinib, con las estructuras de KRASwt y KRASG12C. Los acoplamientos entre crizotinib con KRASwt y KRASG12C, respectivamente, muestran valores de energía de interacción (42,77 kcal/mol y 46,20 kcal/mol) muy similares a los obtenidos entre crizotinib y ALK (42,37 kcal/mol). A su vez, alectinib se acopló en el mismo sitio que los fármacos específicos de KRAS y KRASG12C, y presentaron valores de energía de interacción (51,74 kcal/mol y 54,69 kcal/mol, respectivamente) superiores a los obtenidos con ALK (44,94 kcal/mol). Finalmente, la expresión de la vía RAS/MEK nos mostró una disminución significativa de la expresión de RAS en líneas celulares de cáncer de pulmón ALK+ y ALKL1196M tratadas con crizotinib y alectinib. Conclusiones: Las técnicas in silico de este estudio muestran la posibilidad de acoplamiento entre los inhibidores de ALK (crizotinib y alectinib) con la estructura de KRAS. Esto permite sugerir una posible terapia combinada entre inhibidores de KRAS y ALK para los casos de coexistencia de ambas mutaciones, que puede evaluarse en posteriores ensayos con líneas celulares.

ABSTRACT Objective: Patients with non-small cell lung cancer positive for the anaplastic lymphoma kinase (ALK+) gene mutation who also have mutations in the Kirsten rat sarcoma (KRAS) gene, such as KRAS G12C, are showing resistance to both anaplastic lymphoma kinase (ALK) gene and KRAS inhibitors. Therefore, the interaction between ALK inhibitors and KRAS was analyzed to suggest a synergy between them. Materials and methods: The study performed homology modeling of the KRASwt, KRAS G12C and ALKwt structures. Subsequently, molecular dockings were carried out to determine the binding energy of ALK and KRAS inhibitors and to evaluate the possible interaction of ALK inhibitors with KRAS and the KRAS G12C structure. Finally, the expression in the RAS/MEK pathway was analyzed using the Western Blot technique. Results: The binding energy values show the potential interaction of ALKwt inhibitors, such as crizotinib and alectinib, with the KRASwt and KRAS G12C structures. The binding of crizotinib to KRASwt and KRAS G12C, respectively, indicates interaction energy values (42.77 kcal/mol and 46.20 kcal/mol) which are very similar to those obtained between crizotinib and ALK (42.37 kcal/mol). In turn, alectinib bound to the same site as drugs targeting KRAS and KRAS G12C, and showed interaction energy values (51.74 kcal/mol and 54.69 kcal/mol, respectively) higher than those obtained with ALK (44.94 kcal/mol). Finally, a significant decrease in RAS expression within the RAS/MEK pathway was observed in ALK+ and ALK 1196M lung cancer cell lines treated with crizotinib and alectinib. Conclusions: In silico techniques of this study demonstrate the potential binding of ALK inhibitors (crizotinib and alectinib) to the KRAS structure. In addition, this allows suggesting a possible combined therapy between KRAS and ALK inhibitors for cases of coexistence of both mutations that can be assessed in subsequent trials with cell lines.

Nuevos paradigmas en atrofia muscular espinal de presentación temprana: siempre es bueno recordar / New paradigms in early-onset spinal muscular atrophy: a reminder is always beneficial

La atrofia muscular espinal (AME) de presentación temprana representa la variante más severa, con una expectativa de vida generalmente no mayor a dos años sin soporte ventilatorio, debido a la insuficiencia respiratoria y la dificultad para toser. Tradicionalmente, el manejo respiratorio en muchos países ha incluido la traqueostomía para proporcionar asistencia ventilatoria invasiva de manera continua. No obstante, la introducción de medicamentos de precisión ha modificado la progresión natural de la enfermedad, evidenciando mejoras significativas en los hitos motores y beneficiando también la función respiratoria. A pesar de estas mejoras, en muchos casos sigue siendo necesaria la ventilación intermitente y/o continua, además de la facilitación de la tos. Estas necesidades pueden abordarse de forma no invasiva mediante el soporte ventilatorio no invasivo (SVN), la in-exsuflación mecánica (IEM) y el reclutamiento de volumen pulmonar (RVP), que son considerados pilares del tratamiento respiratorio en enfermedades neuromusculares. Estas estrategias promueven el desarrollo y mantenimiento de la función respiratoria, reduciendo el riesgo de exacerbaciones respiratorias que podrían llevar a intubaciones evitables. Comúnmente, los pacientes con AME experimentan intentos fallidos de extubación siguiendo protocolos tradicionales, siendo catalogados como no extubables y potenciales candidatos a traqueostomía. No obstante, existen protocolos de extubación específicos para AME que emplean SVN e IEM con un alto porcentaje de éxito, evitando traqueostomías innecesarias que pueden complicar la progresión de la enfermedad y afectar la calidad de vida. El enfoque respiratorio no invasivo es una opción de manejo segura tanto en el hospital como en el hogar, ofreciendo una mejor calidad de vida para los pacientes y sus familias.

Early-onset spinal muscular atrophy (SMA) is the most severe variant, with a life expectancy generally not exceeding two years without ventilatory support due to respiratory insufficiency and difficulty in coughing. Traditionally, respiratory management in many countries has included tracheostomy to provide continuous invasive ventilatory support. However, the introduction of precision medicine has altered the natural progression of the disease, showing significant improvements in motor milestones and also benefiting respiratory function. Despite these improvements, many cases still require intermittent and/or continuous ventilation, as well as cough facilitation. These needs can be addressed non-invasively through non-invasive ventilatory support (NIV), mechanical insufflation-exsufflation (MIE), and lung volume recruitment (LVR), which are considered the pillars of respiratory treatment in neuromuscular diseases. These strategies promote the development and maintenance of respiratory function, reducing the risk of respiratory exacerbations that could lead to avoidable intubations. Commonly, SMA patients experience failed extubation attempts following traditional protocols, being labeled as non-extubatable and potential candidates for tracheostomy. Nevertheless, there are specific extubation protocols for SMA that employ NIV and MIE with a high success rate, avoiding unnecessary tracheostomies that can complicate disease progression and impact quality of life. The non-invasive respiratory approach is a safe management option both in the hospital and at home, offering a better quality of life for patients and their families.

Fisiopatología de la displasia broncopulmonar / Pathophysiology of bronchopulmonary dysplasia

La fisiopatología de la displasia broncopulmonar (DBP) se centra en la interrupción del desarrollo pulmonar durante etapas críticas en las que la histología, anatomía y función celular están en proceso de adaptación para facilitar el intercambio gaseoso eficiente. Este desarrollo, que avanza hacia la etapa alveolar después de la etapa sacular, ocurre simultáneamente con una respuesta inflamatoria y de reparación al daño. Como resultado, se afectan la vía aérea (principalmente a través de la limitación obstructiva), los alvéolos (resultando en hipoxemia) y la vasculatura pulmonar (provocando hipertensión pulmonar).

The pathophysiology of bronchopulmonary dysplasia (BPD) is centered on the disruption of lung development during critical stages where histology, anatomy, and cellular function are adapting to facilitate efficient gas exchange. This development, advancing towards the alveolar stage after the saccular stage, occurs concurrently with an inflammatory and damage repair response. As a result, it affects the airway (primarily through obstructive limitation), alveoli (resulting in hypoxemia), and pulmonary vasculature (leading to pulmonary hypertension).

Upregulation of PGC-1α expression by pioglitazone mediates prevention of sepsis-induced acute lung injury

Abstract The imbalance between pro-inflammatory M1 and anti-inflammatory M2 macrophages plays a critical role in the pathogenesis of sepsis-induced acute lung injury (ALI). Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) may modulate macrophage polarization toward the M2 phenotype by altering mitochondrial activity. This study aimed to investigate the role of the PGC-1α agonist pioglitazone (PGZ) in modulating sepsis-induced ALI. A mouse model of sepsis-induced ALI was established using cecal ligation and puncture (CLP). An in vitro model was created by stimulating MH-S cells with lipopolysaccharide (LPS). qRT-PCR was used to measure mRNA levels of M1 markers iNOS and MHC-II and M2 markers Arg1 and CD206 to evaluate macrophage polarization. Western blotting detected expression of peroxisome proliferator-activated receptor gamma (PPARγ) PGC-1α, and mitochondrial biogenesis proteins NRF1, NRF2, and mtTFA. To assess mitochondrial content and function, reactive oxygen species levels were detected by dihydroethidium staining, and mitochondrial DNA copy number was measured by qRT-PCR. In the CLP-induced ALI mouse model, lung tissues exhibited reduced PGC-1α expression. PGZ treatment rescued PGC-1α expression and alleviated lung injury, as evidenced by decreased lung wet-to-dry weight ratio, pro-inflammatory cytokine secretion (tumor necrosis factor-α, interleukin-1β, interleukin-6), and enhanced M2 macrophage polarization. Mechanistic investigations revealed that PGZ activated the PPARγ/PGC-1α/mitochondrial protection pathway to prevent sepsis-induced ALI by inhibiting M1 macrophage polarization. These results may provide new insights and evidence for developing PGZ as a potential ALI therapy.

Edema pulmonar por reexpansión. Reporte de Caso / Pulmonary edema due to re-expansion. Case Report

Introducción. El edema pulmonar por reexpansión es una complicación poco frecuente, secundaria a una rápida reexpansión pulmonar posterior al drenaje por toracentesis o toracostomía cerrada. Al día de hoy, se ha descrito una incidencia menor al 1 % tras toracostomía cerrada, con mayor prevalencia en la segunda y tercera década de la vida. Su mecanismo fisiopatológico exacto es desconocido; se ha planteado un proceso multifactorial de daño intersticial pulmonar asociado con un desequilibrio de las fuerzas hidrostáticas. Caso clínico. Presentamos el caso de un paciente que desarrolló edema pulmonar por reexpansión posterior a toracostomía cerrada. Se hizo una revisión de la literatura sobre esta complicación. Resultados. Aunque la clínica sugiere el diagnóstico, la secuencia de imágenes desempeña un papel fundamental. En la mayoría de los casos suele ser autolimitado, por lo que su manejo es principalmente de soporte; sin embargo, se han reportado tasas de mortalidad que alcanzan hasta el 20 %, por tanto, es importante conocer los factores de riesgo y las medidas preventivas. Conclusión. El edema pulmonar de reexpansión posterior a toracostomía es una complicación rara en los casos con neumotórax, aunque es una complicación que se puede presentar en la práctica diaria, por lo cual debe tenerse en mente para poder hacer el diagnóstico y un manejo adecuado.

Introduction. Re-expansion pulmonary edema is a rare complication secondary to rapid pulmonary re-expansion after drainage by thoracentesis and/or closed thoracostomy. As of today, an incidence of less than 1% has been described after closed thoracostomy, with a higher prevalence in the second and third decades of life. Its exact pathophysiological mechanism is unknown; a multifactorial process of lung interstitial damage associated with an imbalance of hydrostatic forces has been proposed. Clinical case. We present the case of a patient who developed pulmonary edema due to re-expansion after closed thoracostomy, conducting a review of the literature on this complication. Results. Although the clinic suggests the diagnosis, the sequence of images plays a fundamental role. In most cases, it tends to be a self-limited disease, so its management is mainly supportive. However, mortality rates of up to 20% have been recorded. Therefore, it is important to identify patients with major risk factors and initiate preventive measures in these patients. Conclusions. Re-expansion pulmonary edema after thoracostomy is a rare complication in cases with pneumothorax; however, it is a complication that can occur in daily practice. Therefore, it must be kept in mind to be able to make the diagnosis and an adequate management.

Costos directos del tratamiento de la tuberculosis pulmonar en pacientes adherentes y no adherentes en un hospital público de la Ciudad Autónoma de Buenos Aires / Direct Costs of the Treatment of Pulmonary Tuberculosis in Adherent and Non- Adherent Patients in a Public Hospital of the City of Buenos Aires

ABSTRACT Objetivo: Determinar costos directos del tratamiento en tres grupos de pacientes con tuberculosis pulmonar (TP): ambulatorios-adherentes (AA), hospitalizados adherentes (HA) y hospitalizados no adherentes (HNA). Material y métodos: Se consideraron tres grupos: ambulatorios-adherentes, hospitaliza dos adherentes y hospitalizados no adherentes. Se determinaron costos directos desde la perspectiva del financiador, según modulación del Gobierno de la Ciudad de Buenos Aires a julio 2022, cotización peso/dólar 140. El costo de las drogas antituberculosis fue provisto por el Programa de Tuberculosis del Gobierno de la Ciudad de Buenos Aires. Resultados: Se incluyeron 10 pacientes ambulatorios adherentes. El tiempo de trata miento fue de 24 ± 2,52 semanas; la adherencia, el 100 %. El costo directo fue de USD 257,79 por paciente (RIQ = 191,6-328,55). Se incluyeron 20 pacientes hospitalizados no adherentes y 10 hospitalizados adherentes, sin diferencias en edad y género entre ellos. Los primeros tenían mayor carga tabáquica, situación de calle, desnutrición, al coholismo, adicciones y HIV (todos p < 0,05). El tiempo de primer tratamiento fue para hospitalizados no adherentes 5,5 semanas (RIQ = 3-8) y 24 semanas para hospitalizados adherentes. La duración en hospitalizados no adherentes de siguientes tratamientos fue de 0,5-9 semanas. El costo final alcanzó USD 8165,87 por paciente (RIQ = 4706,45- 12 897,82) en hospitalizados no adherentes y USD 4015,26 (RIQ = 3458,15-4482,6), en hospitalizados adherentes (p < 0,01). Conclusión: El costo directo del tratamiento en ambulatorios adherentes fue USD 257 por paciente. El costo directo del abandono del tratamiento de hospitalizados no adherentes es el doble que en hospitalizados adherentes (USD 8165 vs. USD 4015). El costo de tratar a ambulatorios adherentes es quince veces menor que internarlos. Es el primer estudio de costos directos en nuestro país sobre el tema. Se deben instrumentar programas de mejora de adherencia al tratamiento para evitar un alto costo sanitario, drogorresistencia y aumento de la morbimortalidad.

ABSTRACT Objective: To determine the direct costs of the treatment in three groups of patients with pulmonary tuberculosis (PTB): adherent outpatients (AOs), hospitalized-adherent (HA), and hospitalized non-adherent (HNA). Methods: Three groups were considered: AOs, HA, and HNA patients. Direct costs were determined from the perspective of the funder, based on the cost modules pro-vided by the Government of the City of Buenos Aires (GCBA) as of July 2022, with a peso/dollar exchange rate of 140. The cost of antituberculous drugs was provided by the Tuberculosis Program of the GCBA. Results: Ten AOs were included, with a treatment duration of 24±2.52 weeks and 100 % adherence. The direct cost was US$ 257.79 per patient (IQR [inter quartile range]=191.6-328.55). Twenty HNA patients and ten HA patients were included, with no differences between the groups in age and gender. HNA patients showed the following characteristics: higher smoking load, homelessness, malnutrition, alcoholism, addictions, and HIV (all p<0.05). The duration of the first treatment was 5.5 weeks for HNA patients (IQR=3-8), and 24 weeks for HA patients. The duration of subsequent treatments for HNA patients ranged from 0.5 to 9 weeks. The final cost was US$ 8,165.87 per patient (IQR=4,706.45-12,897.82) in the HNA group and US$ 4,015.26 per patient (IQR=3,458.15-4,482.6) in the HA group (p<0.01). Conclusion: The direct cost of treatment in AOs was US$ 257 per patient. The direct cost of treatment withdrawal in HNA patients is twice the cost of HA patients (US$ 8,165 vs. US$ 4,015). The cost of treating AOs is fifteen times lower than the cost of hospitalizing them. This is the first study about direct costs on this topic to be conducted in our country. Programs to improve treatment adherence should be implemented to prevent high healthcare costs, drug resistance, and increased morbidity and mortality.

Clinical Observation on the Acupuncture at Neiyingxiang Points Combined with Western Medicine in the Treatment of Allergic Rhinitis of Deficiency-Cold of Lung Qi Type / 广州中医药大学学报

Objective To observe the clinical efficacy of acupuncture at Neiyingxiang(EX-HN09)points combined with western medicine in the treatment of allergic rhinitis of deficiency-cold of lung qi type.Methods Sixty patients with deficiency-cold of lung qi type of allergic rhinitis were randomly divided into observation group and control group,with 30 patients in each group.The control group was treated with Desloratadine Tablets combined with Mometasone Furoate Aqueous Nasal Spray,and the observation group was treated with acupuncture at Neiyingxiang points combined with the self-made rhinitis recipe on the basis of the control group,and the clinical efficacy of the two groups was evaluated after 14 days.The changes of nasal symptom scores,Visual Analogue Scale(VAS)and rhinoconjunctivitis quality of life scores of the patients of the two groups were observed before and after the treatment.After 14 days of treatment,the clinical efficacy of the two groups was evaluated.The changes in nasal symptom scores,as well as VAS and rhinoconjunctivitis quality of life questionnaire(RQLQ)scores were observed before and after treatment.The changes in traditional Chinese medicine(TCM)sydnrome scores and serum immunoglobulin E(IgE)were compared before and after treatment in the two groups,and the safety of the two groups was evaluated.Results(1)The total effective rate of the observation group was 93.33%(28/30),and the control group was 73.33%(22/30).The efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the symptoms of nasal congestion,sneezing,runny nose and nasal itching were significantly improved in the two groups(P＜0.01),and the observation group was significantly superior to the control group in improving nasal symptoms,and the differences were statistically significant(P＜0.05).(3)After treatment,the VAS scores of patients in the two groups were significantly improved(P＜0.01),and the observation group was superior to the control group in improving VAS scores,with statistically significant differences(P＜0.05).(4)After treatment,the PQLQ scores of patients in the two groups improved significantly(P＜0.01),and the observation group was significantly superior to the control group in improving the PQLQ scores,and the difference was statistically significant(P＜0.05).(5)After treatment,the TCM syndrome scores of the patients in the two groups were significantly improved(P＜0.01),and the observation group was significantly superior to the control group in improving TCM syndrome scores,with statistically significant differences(P＜0.05).(6)After treatment,the serum IgE levels of patients in the two groups were significantly improved(P＜0.01),and the observation group was significantly superior to the control group in improving serum IgE levels(P＜0.05),with a statistically significant difference.(7)There was no significant difference in the incidence of adverse reactions between the observation group and the control group(P＞0.05).Conclusion Acupuncture at Neiyingxiang points plus self-made rhinitis recipe combined with western medicine in the treatment of deficiency-cold of lung qi type of allergic rhinitis can significantly improve the clinical symptoms of the patients,thus improving the quality of life of the patients,and the therapeutic efficacy is remarkable.

Study on the Treatment of Dampness Stagnated in the Triple Energizer Based on the Theory of"Qi Transformation Leading to the Removal of Pathogenic Dampness" / 广州中医药大学学报

The statement of"qi transformation leading to the removal of pathogenic dampness"was recorded in Wen Bing Tiao Bian(Analysis on Epidemic Febrile Diseases)written by the Qing Dynasty physician WU Ju-Tong.Dampness in the triple energizer is caused by the dysfunction of qi transformation,and the treatment of dampness must be based on the activation of qi movement and focused on the promotion of qi movement and the restoration of the qi transformation in the triple energizer.For the treatment of dampness attack in the upper energizer,therapies of dispersing lung to smooth qi and resolving dampness to relieve the obstruction are recommended.For the treatment of dampness obstruction in the middle energizer,therapy of activating spleen qi by strengthening spleen and moving qi is stressed for helping the removal of dampness and for the eradication of the source of dampness.For the treatment of dampness stagnation in the lower energizer,therapy of draining dampness with sweet-light medicines and activating yang can be used according to the illness status.The three methods of treating dampness,namely dispersing the upper energizer,activating the middle energizer and draining the lower energizer,all embody the mechanism of"qi transformation leading to the removal of pathogenic dampness",and the therapies of dispersing lung with light medicines,inducing perspiration by opening striated layer,eliminating dampness with aromatics and draining dampness with sweet-light medicines should be used in accordance with the syndromes.The elucidation of the academic thoughts of"qi transformation leading to the removal of pathogenic dampness"can provide theoretical reference for the fundamental research of dampness syndrome and clinical application of therapies for resolving dampness in Chinese medicine.

Effects of lncRNA FEZF1-AS1 on proliferation,migration and invasion through regulating EZH2 of lung interstitial cells / 基础医学与临床

Objective To investigate the effects of long non-coding RNA FEZ family zinc finger 1 antisense RNA 1(lncRNA FEZF1-AS1)on enhancer of zeste homolog 2(EZH2)in regulation of proliferation,migration,invasion and epithelial-mesenchymal transition(EMT)of pulmonary interstitial cells and its mechanism.Methods The A549 cells human lung adenocarcinoma cell line were divided into control group and model group[model cells were induced into lung interstitial cells after being treated with transforming growth factor β1(TGF-β1)20 ng/mL for 48 h].The protein expression of E-cadherin,N-cadherin and vimentin in each group was detected by Western blot.The expression of lncRNA FEZF1-AS1 and EZH2 in the two groups was detected by RT-qPCR.Cells in the trans-fection group were divided into si NC group,lncRNA FEZF1-AS1+OE vector group and si lncRNA FEZF1-AS1+OE EZH2 group.Cell proliferation was examined by CCK-8 method,cell migration was detected by cell scratch,and cell invasion was detected by Transwell assays.The protein expression of E-cadherin,N-cadherin,vimentin and EZH2 in each group was detected by Western blot.The direct binding effect of FEZF1-AS1 and EZH2 was deter-mined by RNA immuno-precipitation(RIP).Results Compared with the control group,the protein expression level of E-cadherin in the model group was significantly decreased(P＜0.05),and the protein expression of N-cadherin and vimentin was significantly increased(P＜0.05).Compared with the control group,the expression level of lncRNA FEZF1-AS1 and EZH2 genes was significantly increased in the model group(P＜0.05).Compared with si NC group,the proliferation,migration and invasion ability of si lncRNA FEZF1-AS1+OE vector group were decreased,the ex-pression of E-cadherin protein was increased while the expression of N-cadherin,vimentin and EZH2 was decreased(P＜0.05).Compared with si lncRNA FEZF1-AS1+OE vector group,the proliferation,invasion and migration of si lncRNA FEZF1-AS1+OE EZH2 group were increased(P＜0.05).E-cadherin expression was decreased,while N-cad-herin,vimentin and EZH2 expressions were increased(P＜0.05).RIP experiment further confirmed that lncRNA FEZF1-AS1 had direct binding effect with EZH2.Conclusions LncRNA FEZF1-AS1 can promote the proliferation,invasion,metastasis and EMT process of pulmonary fibrosis cells by regulating EZH2.

Serum CA211 level and NK cell number are associated with prognosis of patients with non-small cell lung cancer / 基础医学与临床

Objective To exploring the correlation between the expression level of serum carbohydrate antigen 211(CA211)and the number of natural killer(NK)cells and prognosis in non-small cell lung cancer(NSCLC)pa-tients.Methods 132 NSCLC patients admitted to the Affiliated Hospital of Hangzhou Normal University from June 2019 to July 2022 were selected as the test group,and 132 patients with benign lung lesions during the same period were selected as the control group.Data were collected from the laboratory to analyze the relationship between serum CA211 expression and NK cell count in NSCLC with clinical prognosis,as well as the related factors affecting the prognosis of NSCLC patients.Results The neutrophil to lymphocyte ratio(NLR)and serum CA211 expression in the test group were higher than those in the control group(P＜0.05),while the count of NK cells was less than that in the control group(P＜0.05);The expression level of serum CA211 in the test group was negatively cor-related with the count of NK cells(r=-0.405,P＜0.001);There were significant differences in lymph node metastasis and TNM staging among patients with different levels of serum CA211 expression and NK cell count(P＜0.05);The one-year survival rate of patients with low expression of CA211 was significantly higher than that of patients with high expression of CA211(P＜0.05),and the one-year survival rate of patients with high count of NK cells was higher than that of patients with low count of NK cells(P＜0.05);Lymph node metasta-sis,TNM staging and CA211 level were all risk factors affecting the prognosis of NSCLC patients(P＜0.05),while counting of NK cells was protective factor for the prognosis of NSCLC patients(P＜0.05).Conclusions The level of serum CA211 and the number of NK cells in NSCLC patients are closely related to pathological characteristics and clinical prognosis.

Efficacy of cinobufacini capsule combined with docetaxel plus cisplatin chemotherapy for the treatment of non-small cell lung cancer / 基础医学与临床

Objective To investigate the impacts of cinobufotalin combined with docetaxel+cisplatin chemotherapy on the disease control and the level of vascular endothelial growth factor(VEGF)in serum of patients with non-small cell lung cancer.Methods Totally 70 patients with non-small cell lung cancer admitted to Zhejiang Veteran Hospital from March 2019 to March 2022 were included.They were randomly divided into combination group(cinobufotalin combined with docetaxel+cisplatin,n= 35)and control group(docetaxel+cisplatin chemotherapy alone,n=35).The disease control rates of two groups,serum VEGF level,carcinoembryonic antigen(CEA),cy-tokeratin 19(CK19)and carbohydrate antigen 125(CA125)were measured using ELISA;life quality of patients was evaluated with the KPS score;The adverse events between two groups were compared.Results The disease control rate in the combination group(33/35,94.29％)was higher than that that of control group(25/35,71.43％,)(P＜0.05).After treatment,the level of VEGF in both groups of patients decreased,and the KPS score increased(P＜0.05)especially in the combination group(P＜0.05).After treatment,the level of serum CEA,CA125,and CK19 of control group and combination group were obviously lower than those before treatment(P＜0.05),while those in the combination group were even lower(P＜0.05).The incidence of adverse events in the combination group(5/35,14.29％)was lower than that in the control group(13/35,37.14％)(P＜0.05).Conclusions Cinobufotalin combined with docetaxel+cisplatin chemotherapy as a potential new chemotherapy significantly reduces the level of VEGF and tumor biomarkers in serum factor,improves the life quality of patients.The combined therapy is proved tobe safe.