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)

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.

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.

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.

The effects of temozolomide combined with γ-fractional stereotactic radiotherapy on the expression of S100B and exosomal microRNA-330 for non-small cell lung cancer patients with brain metastases / 中国医师进修杂志

Objective:To investigate the effects of temozolomide combined with γ-fractional stereotactic radiotherapy on the expression of S100B and exosomal microRNA-330(miR-330) in the treatment of non-small cell lung cancer (NSCLC) patients with brain metastases.Methods:A total of 82 patients with NSCLC brain metastases from February 2018 to October 2020 were selected prospectively, and they were divided into the control group and the observation group by the random number table method, each with 41 patients. The control group received γ-fractional stereotactic radiotherapy, and the observation group received temozolomide on the basis of the control group. The therapeutic efficacy and prognosis of the two groups were compared, and the levels of serum myelin basic protein (MBP), neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP) levels, liver and kidney function indexes, serum S100B, carcinoembryonic antigen (CEA), exosomal miR-330 were compared between the two groups before and after the treatment. The neurologic function of the patients were evaluated by Mini Mental State Examination (MMSE) and National Institutes Health Stroke Scale (NIHSS).Results:The total remission rate in the observation group was higher than that in the control group: 65.85%(27/41) vs. 34.15%(14/41), there was statistical differences ( χ2 = 8.24, P<0.05), but the disease control rate between the two groups had no significant difference ( P>0.05). After the treatment, the levels of serum MBP, GFAP and NSE in the observation group were lower than those in the control group: (10.13 ± 2.07) μg/L vs. (14.39 ± 2.58) μg/L, (0.57 ± 0.12) μg/L vs. (0.75 ± 0.16) μg/L, (5.09 ± 1.16) μg/L vs. (7.17 ± 1.35) μg/L, there were statistical differences ( P<0.05). The levels alanine aminotransferase, blood urea nitrogen and serum creatinine after treatment between the two groups had no significant differences ( P>0.05). After the treatment, the NIHSS scores in the observation group was lower than that in the control group, MMSE scores was higher than that in the control group: (4.16 ± 0.52) scores vs. (4.73 ± 0.44) scores, (22.07 ± 2.51) scores vs. (20.68 ± 2.19) scores, there were statistical differences ( P<0.05). After treatment, the serum levels of S100B and CEA in the observation group were lower than those in the control group, and the expression of exosomal miR-330 was higher than that in the control group: (62.37 ± 10.54) mg/L vs. (68.05 ± 9.39) mg/L, (12.61 ± 2.05) μg/L vs.(14.08 ± 1.97) μg/L, 0.49 ± 0.12 vs. 0.42 ± 0.05, there were statistical differences ( P<0.05). The median survival time in the observation group was 14.6 months, while that in the control group was 11.50 months. There were no significant differences in the incidence of adverse reactions between the two groups ( P>0.05). Conclusions:Treatment with temozolomide combined with γ-fractional stereotactic radiotherapy for NSCLC patients with brain metastases can improve the therapeutic efficacy, neurological function, inhibit the expression of serum S100B, CEA and exosomal miR-330, and prolong the survival time of patients.

Clinical significance of changes in peripheral blood angiotensin-converting enzyme 2, high mobility group protein B1 and interleukin-33 levels in patients with primary lung cancer complicated by pulmonary infection after surgery / 中国医师进修杂志

Objective:To investigate the changes in peripheral blood angiotensin-converting enzyme 2 (ACE2), high mobility group protein B1 (HMGB1) and interleukin 33 (IL-33) levels and their clinical significance in patients with primary lung cancer complicated by lung infection after surgery.Methods:The clinical data of 92 primary lung cancer patients treated at Longchang People′s Hospital from August 2018 to February 2021 were retrospectively collected, they were underwent radical lung cancer surgery, and were divided into the pulmonary infection group(27 cases) and the non-pulmonary infection group(65 cases) according to whether the patients had postoperative complications of pulmonary infection. The clinical data, peripheral blood ACE2, HMGB1 and IL-33 levels before and after surgery between the two groups were compared. The risk factors associated with postoperative pulmonary infection were analyzed by Lasso regression and Logistic regression. The predictive value of pulmonary infection was analyzed by receiver operating characteristic (ROC) curve. The cut-off values of peripheral blood ACE2, HMGB1 and IL-33 in the ROC curve were used as the boundary to divide the high level group and low level group, and the Kaplan-Meier survival curve was drawn to compare the survival rates of patients with high levels and low levels of peripheral blood ACE2, HMGB1 and IL-33.Results:The incidence of chronic obstructive pulmonary disease in the pulmonary infection group was higher than that in the non-pulmonary infection group: 40.74%(11/27) vs. 15.38%(10/65), there was statistical difference ( χ2 = 6.96, P<0.05). The levels of postoperative peripheral blood ACE2, HMGB1 and IL-33 in the pulmonary infection group were higher than those in the non-pulmonary infection group: (36.87 ± 9.87) mg/L vs. (25.94 ± 8.69) mg/L, (24.49 ± 8.14) μg/L vs. (16.74 ± 5.07) μg/L, (51.48 ± 8.25) ng/L vs. (39.88 ± 6.85) ng/L, there were statistical differences ( P<0.05). The results of Lasso regression and Logistic regression showed that the chronic obstructive pulmonary disease, postoperative peripheral blood ACE2, HMGB1 and IL-33 levels were independent risk factors for postoperative complications of pulmonary infection in patients with primary lung cancer ( P<0.05). The results of ROC curve showed that the area under the curve(AUC) values for postoperative peripheral blood ACE2, HMGB1 and IL-33 levels predicting postoperative complications of lung infection were 0.705, 0.821 and 0.768, respectively, and the AUC for the combination was 0.935. The risk of death in patients with high levels of postoperative peripheral blood ACE2, HMGB1 and IL-3 were 7.500, 4.874 and 2.857 times than the patients with low levels. Conclusions:Postoperative peripheral blood ACE2, HMGB1 and IL-3 levels in patients with primary lung cancer are important factors for pulmonary infection, which can be used for early prediction and evaluation after operation.

EGFR Methylation in Peripheral Blood of Driver Gene-Positive Lung Cancer and its Clinical Correlation / 医学研究杂志

Objective To explore the methylation status of EGFR promoter region in peripheral blood of EGFR driver gene-positive lung adenocarcinoma patients and its clinical significance.Methods The methylation of EGFR promoter region in peripheral blood DNA of 32 EGFR driver gene-positive lung adenocarcinoma patients and 24healthy controls were detected by(matrix-assisted laser desorp-tion/ionisation,time-of-flight mass spectrometry,MALDI-TOF MS)technique to screen the differential methylation of CpG sites with lung cancer and analyze its correlation with clinicopathological characteristics and EGFR mutant subtype.Results The methylation levels of EGFR were significantly lower in the lung cancer group than in the normal control,EGFR#29 CpG_2,EGFR#30 CpG_8.9.10.11,CpG_25,CpG_40.41.42methylation of lung cancer group(25.7％±2.1％,4.6％±0.4％,2.8％±0.7％,4.40±0.4％)were low-er than the normal control(36.5％±4.6％,6.0％±0.6％,4.8％±0.9％,7.1％±0.4％),the difference was statistically signifi-cant(P＜0.05).No significant differences in the methylation levels within EGFR CpGs were associated with age,cancer differentiation,disease location,TNM stage with lung cancer(P＞0.05).The methylation level of EGFR#30 CpG_25 in the female group was signifi-cantly lower than that in the male group(P＜0.05),and the methylation level of EGFR#30 CpG_25 in the smoking group was higher than that in the non-smoking group(P＜0.05),the methylation level of EGFR#30 CpG_8.9.10.11 in the lymph node metastasis group was significantly lower than that in the non-lymph node metastasis(P＜0.01).There was no significant difference in methylation of EGFR between EGFR 19del and 21 L858R mutant subtypes.Conclusion Our findings suggest that EGFR methylation may be associated with the occurrence,development,gender,and smoking history of patients with EGFR driving gene-positive lung cancer,which may serve as a biomarker for the diagnosis and prognosis prediction of lung cancer.

Immunotherapy Strategy for Advanced Non-Small Cell Lung Cancer in the Elderly / 医药导报

Immunotherapy,represented by immune checkpoint inhibitors(ICIs),has significantly changed the treat-ment strategy of non-small cell lung cancer(NSCLC)and has become an important therapy for all stages of NSCLC.However,there is an urgent need for further clarification regarding ICIs for elderly patients with advanced NSCLC.Treatment strategies for ICIs were guided by assessing survival data of elderly NSCLC patients included in clinical trials.We concluded that treatment regi-mens such as ICI monotherapy,dual immunotherapy,and ICIs combined with chemotherapy could be carried out in elderly NSCLC patients with a performance status(PS)score<2.Elderly NSCLC patients treated with ICIs could achieve similar benefits as younger patients and are generally well tolerated.However,as age increases(especially above 80 years),the efficacy decreased and the incidence of immune-related adverse events(irAEs)gradually increased.Therefore,ICIs should be carefully selected for advanced NSCLC patients at an advanced age.Compared to age,PS was a key factor causing patients to be excluded from ICIs and poorer survival outcomes.In conclusion,immunotherapy in elderly patients with advanced NSCLC is extremely challenging,and many issues still need further exploration in this field.

Jinyinqingre Oral Liquid Alleviates Acute Lung Injury in Mice through NF-κB/NLRP3 Signaling Pathway / 医药导报

Objective To explore the protective effect and mechanism of Jinyinqingre oral liquid on acute lung injury in-duced by lipopolysaccharide(LPS)in mice.Methods C57BL/6J mice were randomly divided into six groups according to the random number table method:blank control group,model control group,Jinyinqingre oral liquid low-dose group,Jinyinqingre oral liquid medium-dose group,Jinyinqingre oral liquid high-dose group,and dexamethasone group.Except for the blank control group,the other groups were injected with lipopolysac charide(LPS)(5 mg·kg-1)into the trachea to establish the acute lung injury model of mice,and the Jinyinqingre oral liquid low,medium,and high groups were continuously administered the drug by gavage for three days.After 24 h,lung tissue and bronchoalveolar lavage fluid(BALF)were collected from the six groups for follow-up detection.The pathological injury of lung tissue in each group was observed by HE staining.The total number of cells in BALF was detected.The to-tal protein content of BALF was detected by the BCA method.The contents of inflammatory cytokines TNF-α,IL-1β,IL-6,and IgM in BALF were detected by ELISA.The expression of NF-κB and NLRP3 proteins in lung tissues was detected by immunohistochemistry and Western blotting.Results Compared with model control group,Jinyinqingre oral liquid alleviated the pathological injury of lung tissue(P＜0.05),decreased the total cell count,total protein content and IgM expression in BALF(P＜0.01),and the expres-sion of inflammatory cytokines TNF-α,IL-6 and IL-1β in BALF was dreased(P＜0.05),the protein expressions of NF-κB and NL-RP3 in lung tissues was dreased(P＜0.05).Conclusion Jinyinqingre oral liquid attenuated the pathological injury,inflammatory exudation,and expression of inflammatory cytokines in LPS-induced lung injury in mice,and its mechanism may be through the reg-ulation of NF-κB/NLRP3 signaling pathway,providing a theoretical basis for its clinical application.

Research progress on H-E stained whole slide image analysis by artificial intelligence in lung cancer / 中国癌症杂志

Pathology is the gold standard for diagnosis of neoplastic diseases.Whole slide imaging turns traditional slides into digital images,and artificial intelligence has shown great potential in pathological image analysis,especially deep learning models.The application of artificial intelligence in whole slide imaging of lung cancer involves many aspects such as histopathological classification,tumor microenvironment analysis,efficacy and survival prediction,etc.,which is expected to assist clinical decision-making of accurate treatment.Limitations in this field include the lack of precisely annotated data and slide quality varying among institutions.Here we summarized recent research in lung cancer pathology image analysis leveraging artificial intelligence and proposed several future directions.

Characterization and correlation analysis of lung flora in rats with silica-induced acute lung injury / 中国病理生理杂志

AIM:To elucidate the possible biological mechanism of silica-induced acute lung injury in rats.METHODS:Sixteen Male Sprague-Dawley rats were divided into control and acute silicosis model groups,and instilled intratracheally with 1 mL of normal saline and 50 g/L silica suspension,respectively.After 7 d,the rats were sacrificed for collection of lung tissue and serum.The serum levels of interleukin-1β(IL-1β),IL-18 and tumor necrosis factor-α(TNF-α)were measured by using ELISA.The protein expression levels of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)and gasdermin D(GSDMD)were measured by immunohistochemistry.Bacterial DNA was ex-tracted from the lung tissue for 16S ribosomal RNA gene sequencing to characterize changes in the composition of lung flo-ra.The differences in the structure of bacterial flora between control and model groups were analyzed by bioinformatic analy-ses.RESULTS:Immunohistochemical analysis showed that the protein expression levels of NLRP3 and GSDMD were higher in the lungs of the rats in model group.In addition,serum cytokine profiling showed that IL-1β,IL-18 and TNF-α levels were significantly higher in model group.The most abundant bacterial genera in the lung flora of the rats in model group were Bifidobacterium,Clostridium sensu stricto 1,and Parasutterella.The NLRP3 and GSDMD levels in the lung tissue and IL-1β and TNF-α levels in serum were positively correlated with the abundance of Parasutterella.CONCLU-SION:The alterations in lung flora structure and increased inflammation levels may be the actual biological mechanisms underlying silica-induced acute lung injury.The modulation of lung flora may provide a basis for the prevention and treat-ment of silica-induced acute lung injury.

Saponin from Panax japonicus IVa alleviates lipopolysaccharide-induced acute lung injury in rats via its anti-inflammatory and antioxidative ef-fects / 中国病理生理杂志

AIM:To investigate the effects of saponin from Panax japonicus IVa(SPJ IVa)on acute lung inju-ry in rats and to explore its possible protective mechanism.METHODS:Sixty SD rats were randomly divided into four groups,15 rats in each group:the control group,model group,low-dose SPJ IVa group,and high-dose SPJ IVa group.A rat model of ALI was established via intratracheal instillation of lipopolysaccharide(LPS,2 mg/kg).Rats in the low-and high-dose SPJ IVa groups were intraperitoneally injected with 15 and 45 mg/kg SPJ IVa,respectively,30 min after model-ing.Serum,bronchoalveolar lavage fluid(BALF),and lungs were collected 24 h after modeling.Pathomorphological changes in lung tissues were assessed using HE staining.The wet weight/dry weight ratio of lung tissues was measured us-ing the weighing method,whereas ELISA was used to measure the levels of interleukin-1β(IL-1β),IL-6,and tumor ne-crosis factor-α(TNF-α)in the serum and BALF.The levels of malondialdehyde(MDA),superoxide dismutase(SOD),and glutathione(GSH)were assessed using the kit method.Cell apoptosis in lung tissues was evaluated by immunohisto-chemical staining of cleaved caspase-3 and TUNEL.Western blot was used to measure the expression of nuclear factor E2-related factor 2(Nrf2),heme oxygenase-1(HO-1),nuclear factor-κB(NF-κB)p65,and Toll-like receptor 4(TLR4)in lung tissues.RESULTS:Compared with control group,the lung tissues of the model group were significantly damaged,and the lung injury scores(0.21±0.22 vs 2.98±0.46)and lung wet/dry weight ratios(3.09±0.41 vs 6.36±0.61)were significantly increased(P<0.01).Compared with model group,the lung injury scores(1.80±0.31 and 1.05±0.25 vs 2.98±0.46)and lung wet/dry weight ratios(5.25±0.44 and 3.89±0.35 vs 6.36±0.61)in low-and high-dose SPJ IVa groups were significantly reduced(P<0.01).The administration of LPS resulted in elevated levels of pro-inflammatory cy-tokines(IL-1β,IL-6,and TNF-α)as well as the oxidative marker MDA in both serum and BALF(P<0.01).Additional-ly,it led to a decrease in antioxidant markers SOD and GSH(P<0.01).However,treatment with both low and high doses of SPJ IVa effectively attenuated the LPS-induced production of pro-inflammatory factors and oxidative markers MDA(P<0.01),while also increasing SOD and GSH levels(P<0.05 or P<0.01).In the model group,evident apoptosis was ob-served in lung tissues,whereas treatment with low and high doses of SPJ IVa significantly suppressed TUNEL-positive cells and the expression of cleaved caspase-3(P<0.01).The expression levels of Nrf2,HO-1,NF-κB p65,and TLR4 in lung tissues were significantly higher in the model group than in the control group(P<0.01);in turn,after treatment with low and high doses of SPJ IVa,Nrf2 and HO-1 were further upregulated(P<0.01),whereas NF-κB p65 and TLR4 were downregulated(P<0.01).CONCLUSION:The inhibitory effect of SPJ IVa on LPS-induced ALI in rats may be attribut-ed to its ability to suppress the TLR4/NF-κB-and Nrf2/HO-1-mediated inflammatory response and oxidative stress.

Effects of total flavonoids of Pterocarya hupehensis Skan on migration,invasion and ferroptosis of non-small-cell lung cancer A549 cells / 中国病理生理杂志

AIM:To investigate the impact of total flavonoids of Pterocarya hupehensis Skan(PHSTF)on the migration,invasion,and ferroptosis of non-small-cell lung cancer A549 cells.METHODS:The A549 cells were divided into control group,low-,medium-and high-dose(100,150 and 200 μg/mL)PHSTF groups,ferroptosis inhibitor liprox-statin-1(Lip-1)group,and high-dose PHSTF combined with Lip-1 group,each cultured in corresponding media.Cell via-bility was assessed using the CCK-8 assay,while cell migration and invasion abilities were determined through scratch and Transwell assays.Cell lipid peroxidation levels were measured using the glutathione(GSH)assay kit.RT-qPCR was em-ployed to assess the mRNA expression of solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4),while Western blot was utilized to examine the protein expression of SLC7A11,GPX4,Kelch-like epichlorohy-drin-associated protein-1(Keap-1),nuclear factor E2-related factor 2(Nrf2)and heme oxygenase-1(HO-1).RE-SULTS:Compared with control group,PHSTF significantly diminished the viability of A549 cells in a time-and dose-de-pendent manner(P＜0.01),and the cell migration and invasion were also reduced(P＜0.01),along with a significant de-crease in GSH level(P＜0.01).Treatment with PHSTF inhibited the mRNA and protein expression levels of ferroptosis-re-lated proteins,including SLC7A11 and GPX4(P＜0.01),suppressed the protein expression of Nrf2 and HO-1(P＜0.01),and enhanced the expression of Keap-1(P＜0.01).The Lip-1 partially restored the decrease in cell viability in-duced by PHSTF(P＜0.01),significantly up-regulated the protein expression levels of SLC7A11,GPX4,Nrf2 and HO-1,and suppressed the protein expression of Keap-1(P＜0.01).CONCLUSION:Total flavonoids of Pterocarya hupehen-sis Skan can inhibit the migration and invasion of non-small-cell lung cancer A549 cells,and induce the cell ferroptosis by regulating the Keap-1/Nrf2/HO-1 pathway.

WIN55212-2 inhibits glycolysis and attenuates acute lung injury in septic mice by regulating mTOR/HIF-1α/PFKFB3 signaling pathway / 中国病理生理杂志

AIM:To investigate the effects of cannabinoid receptor agonist WIN55212-2(WIN)on acute lung injury(ALI)in septic mice,and to explore its potential mechanisms through glycolysis.METHODS:A mouse model of septic ALI was established by intraperitoneal injections of lipopolysaccharide(LPS).Male C57BL/6J mice were randomly divided into 4 groups(n=6):(1)control group;(2)LPS group,receiving intraperitoneal injections of LPS at 10 mg/kg;(3)LPS+WIN group,receiving 1 mg/kg WIN intraperitoneally 30 min prior to LPS injection;(4)LPS+WIN+MHY1485[mammalian target of rapamycin(mTOR)activator]group,receiving 10 mg/kg MHY1485 intraperitoneally 1 d before LPS injection and 1 mg/kg WIN plus 10 mg/kg MHY1485 30 min before LPS injection.Tissues were collected 24 h after modeling for analysis.Lung indexes were calculated,and histopathological changes of lung tissues were observed via he-matoxylin-eosin(HE)staining.Inflammatory cytokines interleukin-1β(IL-1β)and IL-10 in lung tissues,and lactic acid and lactate dehydrogenase A(LDHA)in serum were quantified using ELISA.The levels of mTOR/hypoxia-inducible fac-tor-1α(HIF-1α)/6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3(PFKFB3)signaling pathway-related proteins were assessed by Western blot.RESULTS:Compared with control group,the LPS group exhibited an increased lung in-dex,significant lung tissue damage,an increase in IL-1β levels(P＜0.05),a decrease in IL-10 levels(P＜0.05),and el-evated expressions of lactate and LDHA(P＜0.05),along with increased levels of phosphorylated mTOR(p-mTOR),HIF-1α and PFKFB3 proteins(P＜0.05).The LPS+WIN group showed improvements with a reduced lung index(P＜0.05),lessened lung injury,decreased IL-1β levels(P＜0.05),increased IL-10 levels(P＜0.05),and lower levels of lactic acid,LDHA,p-mTOR,HIF-1α,and PFKFB3(P＜0.05).Conversely,the LPS+WIN+MHY1485 group displayed increased lung indexes and lung tissue damage,elevated IL-1β levels(P＜0.05),reduced IL-10 levels(P＜0.05),and higher expressions of lactic acid,LDHA,p-mTOR,HIF-1α and PFKFB3(P＜0.05)compared to the LPS+WIN group.CONCLUSION:WIN55212-2 mitigates sepsis-induced ALI,potentially by modulating the mTOR/HIF-1α/PFKFB3 sig-naling pathway,thereby inhibiting glycolysis and alleviating inflammatory responses.

Anti-synthase syndrome complicated by multiple organ damage: one-case report and literature analysis / 中国基层医药

Objective:By analyzing the characteristics, diagnosis, and treatment process of anti-synthetase syndrome complicated by interstitial pneumonia and cardiac dysfunction, we aim to enhance general practitioners' understanding and diagnosis of this disease, thereby improving their level of diagnosis and treatment and reducing misdiagnoses and missed diagnoses.Methods:A patient with anti-synthase syndrome complicated by interstitial pneumonia and cardiac dysfunction, who was admitted to The First Affiliated Hospital of Xi'an Medical University in February 2020 due to limb weakness accompanied by paroxysmal cough for 2 years and aggravated symptoms for 10 days, was included in this study. The patient's clinical symptoms, physical signs, laboratory examination results, diagnosis and treatment process, and follow-up were retrospectively analyzed based on previous literature.Results:Through the general practitioner's SOAP consultation, physical examination, and imaging examination, the patient was diagnosed with anti-synthase syndrome complicated by interstitial pneumonia and cardiac dysfunction. Then rheumatology and immunology experts, respiratory medicine experts, and cardiovascular experts collaborated to provide a specialist diagnosis and treatment plan for the patient. Subsequently, the patient was referred to the department of rheumatology and immunology for specialized disease management. Finally, the patient was followed up in the general clinic. After the patient's condition stabilized, she gradually resumed her health.Conclusion:The multidisciplinary diagnosis and treatment scheme for anti-synthase syndrome can enhance general practitioners' understanding of the disease, make the diagnosis of the disease, and fully leverage the advantages of multi-disciplinary consultation and primary diagnosis in general medicine.

Value of peripheral blood NLR, PLR and serum LDH for predicting the occurence of radiation pneumonia in patients with small cell lung cancer / 中国基层医药

Objective:To investigate the value of peripheral blood neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and serum lactate dehydrogenase (LDH) levels for predicting the occurrence of radiation pneumonia (RP) in small cell lung cancer.Methods:A total of 84 patients with small cell lung cancer who received image-guided radiotherapy in Xuzhou Cancer Hospital between September 2019 and September 2022 were retrospectively analyzed. They were divided into an RP group ( n = 25) and a non-RP group ( n = 59) according to whether RP occurred. Peripheral blood NLR and PLR and serum LDH levels were compared between the two groups before and after radiotherapy. The receiver operating characteristic curve (ROC curve) was used to analyze the value of peripheral blood NLR, PLR, and serum LDH levels for the diagnosis of RP in small cell lung cancer. Results:Before radiotherapy, there were no significant differences in peripheral blood NLR and PLR between the two groups (both P > 0.05). After radiotherapy, peripheral blood NLR and PLR in the RP group were (3.39 ± 0.81) and (129.06 ± 24.90), respectively, which were significantly higher than those in the non-RP group [(2.54 ± 0.71), (104.76 ± 26.26), t = 3.61, 3.83, both P < 0.05]. The NLR (2.86 ± 0.30) and PLR (110.07 ± 10.05) were the lowest in patients with grade 2 RP and they were highest in patients with grade 4 RP [(4.49 ± 0.63), (168.88 ± 14.11)]. The grade of RP was positively correlated with peripheral blood NLR and PLR. The sensitivity of peripheral blood NLR in the diagnosis of RP was 88.0%, the specificity was 66.1%, and the area under the curve (AUC) was 0.791. The sensitivity of PLR in the diagnosis of RP was 48.0%, the specificity was 94.9%, and the AUC was 0.735. The sensitivity of NLR combined with PLR in the diagnosis of RP was 92.0%, the specificity was 59.3%, and the AUC was 0.801. There was no significant difference in serum LDH levels between the two groups before and after radiotherapy (both P > 0.05). Logistic regression analysis showed that NLR and PLR were risk factors for RP in patients with small cell lung cancer ( OR = 2.309, 1.037; 95% CI: 1.061-5.024, 1.004-1.071). Conclusion:In patients with small cell lung cancer who develop RP, peripheral blood NLR, and PLR are markedly elevated compared with those in patients who do not develop RP, and combined detection of peripheral blood NLR and PLR has a high value for early diagnosis of RP in patients with small cell lung cancer.

Clinical efficacy of tirellizumab combined with chemotherapy in the treatment of advanced non-small cell lung cancer / 中国基层医药

Objective:To investigate the efficacy of tirellizumab combined with chemotherapy in the treatment of advanced non-small cell lung cancer and its effect on immune function and quality of life in patients.Methods:In this retrospective case-control study, we analyzed the clinical data of 104 patients with advanced (stages III and IV) non-small cell lung cancer who received treatment at Zhoushan Hospital between May 2021 and June 2022. These patients were divided into two groups: group A ( n = 52) and group B ( n = 52), based on the treatment methods utilized. Patients in group A received chemotherapy with gemcitabine plus cisplatin or pemetrexed plus cisplatin. Meanwhile, patients in group B were treated with tirellizumab combined with chemotherapy regimens of gemcitabine plus cisplatin or pemetrexed plus cisplatin, with 21 days as a treatment cycle. Both groups of patients received three cycles of treatment. The short-term efficacy was compared between the two groups. Additionally, serum levels of tumor markers, immune function indexes, quality of life score, and incidence of adverse reactions were compared between the two groups before and after treatment. Results:The short-term response rate in group B was significantly higher than that in group A [51.92% (27/52) vs. 32.69% (17/52), Z = 4.11, P < 0.001]. When compared with pretreatment levels, serum levels of tumor markers and the percentage of CD8 + cells decreased in both groups after treatment. Notably, the serum levels of tumor markers and the percentage of CD8 + cells were significantly lower in group B compared with group A (all P < 0.05). Moreover, after treatment, the percentage of CD4 + cells, the ratio of CD4 +/CD8 + cells, functional subscale, symptom subscale, and total score increased significantly compared with pretreatment levels (all P < 0.05) and were significantly higher in group B compared with those in group A (all P < 0.05). The incidence of adverse events in group B was significantly higher than that in group A [44.23% (23/52) vs. 21.15% (11/52), χ2 = 6.29, P = 0.012]. Conclusion:Tirelizumab combined with chemotherapy is effective for advanced non-small-cell lung cancer. The combined therapy can lower serum levels of tumor markers, restore immune function, and improve overall quality of life.