Progress of blood biomarkers in early prediction of bronchopulmonary dysplasia / 国际儿科学杂志

Bronchopulmonary dysplasia(BPD)is one of the most serious lung disease in the small gestational preterm infants, which may affect their development in infancy and adult quality of life.Blood samples of premature infants are easy to be collected and detected, and their biological markers are helpful for early prediction of BPD, which is of great significance for reducing the incidence of severe BPD and improving the poor prognosis of infants.In recent years, a variety of biological markers have been found in cord blood and serum of premature infants, including matrix metalloproteinase 9, tissue inhibitor of metalloproteinases 1, soluble Klotho protein, vascular endothelial growth factor, interleukin and N-terminal pro-brain natriuretic peptides, etc., some of which have been applied in clinic.It has broad application prospect for screening high-risk premature infants with BPD and effectively predicting the occurrence and severity of early BPD.

Correlation Between Peripheral Blood Biomarkers and Immune Checkpoint Inhibitors in Treatment of Advanced Esophageal Cancer / 肿瘤防治研究

Objective To explore the effect of peripheral blood markers on the efficacy and prognosis of patients with advanced esophageal cancer treated with immune checkpoint inhibitors (ICIs). Methods The case data of 61 patients with advanced esophageal cancer who met the inclusion criteria were collected. Data on clinical indicators and peripheral blood markers as well as objective response rate (ORR) and progression-free-survival (PFS) were obtained. Results The median PFS of the included patients was 7.10 months (95%CI: 5.12-9.07). The ORR of patients with baseline lactate dehydrogenase (LDH) < 201 was better than that of patients with LDH≥201 (P < 0.05). Univariate analysis showed that baseline LDH0 < 201, neutrophil to lymphocyte ratio (NLR) < 3.9, platelet-to-lymphocyte ratio (PLR) < 240.3, and LDH1 < 249.0 two weeks after ICI treatment were significantly associated with significant improvement in PFS (P < 0.05). In multivariate analysis, patients with NLR0 < 3.9 had longer PFS (P < 0.05). Conclusion LDH0 < 201, NLR0 < 3.9, PLR0 < 240.3, and LDH1 < 249.0 are positively correlated with the prognosis of patients with advanced esophageal cancer treated with ICIs.

Prediction of Responses of Patients with Hepatocellular Carcinoma to Anti-PD-1 Immunotherapy by T-cell Invigoration to Tumour Burden Ratio / 肿瘤防治研究

Objective To explore the predictive value of T cell activation in peripheral blood of patients with hepatocellular carcinoma(HCC) after anti PD-1 therapy and its ratio to tumor burden on the efficacy of immunotherapy. Methods Serum specimens were obtained before and after treatment from 85 patients with HCC who received anti-PD-1 treatment. Indicators such as cell subpopulations and T cell activation were detected by flow cytometry. Combined with imaging analysis, cutoff value was obtained by X-tile software. Survival analysis was used to evaluate patients' outcomes. Results The maximum fold change of Ki-67+/PD-1+/CD8+ T cells in treatment cycles and the tumor burden determined by imaging were associated with prognoses. The ratio of T cell Ki-67+/PD-1+/CD8+ expression to tumor burden ratio greater than 0.6 at the first cycle of anti-PD-1 immunotherapy was associated with improvements in progression-free survival and overall survival (P < 0.05). Conclusion The ratio of activationa in T cells in peripheral blood after immunotherapy to the tumor burden may be related to the clinical efficacy of anti-PD-1 immunotherapy for HCC.

Biomarkers related to the treatment of melanoma with immune checkpoint inhibitors / 中华皮肤科杂志

Recently, great breakthroughs have been made in the treatment of melanoma with immune checkpoint inhibitors. However, only a small proportion of patients show a long-lasting response to immunotherapy, and risks of immune-related adverse events and drug resistance have been also increasing along with the emergence of combination treatment. This review summarizes biomarkers related to the efficacy of immune checkpoint inhibitors in the treatment of melanoma, aiming to predict and screen out patients who may benefit from immunotherapy, guide individualized clinical treatment, and reduce the occurrence of drug resistance and adverse reactions.

Preoperative ascending aorta diameter and prognosis analysis of patients with acute type A aortic dissection / 中华胸心血管外科杂志

Objective:To investigate the preoperative ascending aorta diameter in patients with acute type A aortic dissection in the Chinese population, compares and analyze the differences in preoperative blood biomarkers, and evaluate the impact of the preoperative ascending aorta diameter in this part of patients on the short-term prognosis of patients.Methods:A collection of 641 patients with acute type A aortic dissection who were enrolled in the " Acute Aortic Syndrome High-Risk Early Warning and Intervention Study" project from January 2018 to January 2020 were collected. Divide the patients into two groups (group Ⅰ<55 mm, group Ⅱ≥55 mm) according to the preventive intervention value of ascending aorta diameter recommended by the guideline for studying preoperative ascending aorta diameter difference in blood biomarkers and the influence of ascending aorta diameter on the short-term prognosis of patients. All patients had CT scans to assess the diameter of the ascending aorta before operation.Results:In this study, all patients with acute type A aortic dissection had a mean preoperative ascending aorta diameter of (46.9±9.7)mm. The preoperative ascending aorta diameter of all patients was less than 55 mm, accounted for 84.1%. Male patients were more likely to have aortic dissection than females; most patients' age was less than 60 years old. The preoperative blood inflammatory index counts were higher in the ascending aorta diameter ≥55 mm group. However, the long-term prognosis of patients with different ascending aorta diameters before surgery was not apparent in this study. The preoperative survival rate and short-term survival rate of patients with ascending aorta diameter <55 mm were higher than those of other groups, but the difference was not statistically significant.Conclusion:In patients with acute type A aortic dissection, the diameter of the ascending aorta is usually less than 55 mm. Moreover, the blood inflammatory index counts are high in the preoperative ascending aorta diameter ≥55 mm group. Meanwhile, patients with smaller ascending aorta diameter have better survival rate and short-term prognosis.

Desarrollo y validación de técnicas analíticas para la determinación de biomarcadores sanguíneos en ensayos preclínicos. ¿Por qué y para qué? / Development and validation of analytical techniques for the determination of blood biomarkers in preclinical trials. Why and what for?

Resumen El descubrimiento de un nuevo principio activo farmacéutico implica estudios preclínicos, que tienen como objetivo demostrar que es eficaz y seguro para un posterior ensayo en seres humanos. Esto conduce a la necesidad de desarrollar tecnologías que aprovechen las nuevas herramientas analíticas disponi bles dentro de un contexto donde los resultados de las pruebas realizadas, estén plenamente documentados, bajo sistemas de buenas prácticas de laboratorio auditables. En esta revisión se actualizan y describen algunos de los ensayos realizados en la etapa preclínica del desarrollo de un nuevo fármaco y el estado actual de la tecnología analítica empleada para el dosaje de diferentes biomarcadores sanguíneos de interés. Se analizaron los biomarcadores más relevantes, las normativas de validación de las técnicas analíticas empleadas para su determinación y los problemas que se presentan al tratar de aplicarlas.

Abstract New drug discovery involves preclinical studies to demonstrate its effectivity and safety for further tests in humans. This leads to the need to develop technologies that take advantage of the new analytical tools available within a context where the results of the tests carried out are fully documented, under auditable systems of good laboratory practice. This review updates and describes some of the tests carried out in the preclinical stage of the development of a new drug and the current state of the analytical technology used to measure different blood biomarkers of interest. Biomarker parameters were analyzed at the physiological level, considering both the validation regulations of the analytical techniques used for their determination as the problems that arise when trying to apply them, since many of these biomarkers are endogenous compounds in the used matrices.

Blood-based Biomarkers in the Immune Checkpoint Inhibitor Treatment in Non-small Cell Lung Cancer / 中国肺癌杂志

Immune checkpoint inhibitors (ICI) have transformed the treatment landscape of advanced non-small cell lung cancer (NSCLC). Biomarkers are essential for guiding precision immunotherapy. Tissue-based programmed death ligand 1 (PD-L1) expression and tumor mutational burden (TMB) are currently widely used biomarkers for selecting patients for immunotherapy. However, tissue specimens are often difficult to reach and couldn't overcome spatial and temporal heterogeneity. Blood biomarkers offer an alternative non-invasive solution that could provide a complete insight on patient's immune status and tumor as well, and show their potential in predicting the outcome as well as in monitoring response to immunotherapy. In this article, we summarize current knowledge on blood biomarkers in NSCLC patients treated with ICI, and we hope to provide more references for development of novel biomarkers.
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Metabolic dynamics of native lambs fed with Tifton 85 hay or Maniçoba hay associated with the spineless cactus / Dinâmica metabólica de cordeiros nativos alimentados com feno de capim-tifton 85 ou feno de maniçoba associados à palma forrageira

The objective of this study was to evaluate the metabolic response of native lambs fed Tifton 85 hay (Cynodon dactylon) or Maniçoba hay (Manihot pseudoglaziovii) associated with spineless cactus (Nopalea cochenillifera Salm Dyck). Sixteen Morada Nova lambs were used, with a mean initial weight of 19.36±1.48kg, distributed in a randomized block design, with two treatments and eight replications. Dry matter intake was higher for lambs fed Maniçoba hay compared to Tifton hay, while the body weight at slaughter was not influenced by diets. Regarding the blood metabolites, only the serum concentration of urea was influenced, with higher value observed in the lambs that fed the diet containing Tifton hay. When analyzing blood biomarkers, in the different biweekly collections, a linear increase in the blood concentration of urea, glucose, fructosamine, alkaline phosphatase and sodium was observed, as well as a quadratic effect for serum potassium. The other blood metabolites were not influenced in function of the collection days. The replacement of Tifton 85 hay for Maniçoba hay does not cause negative changes in the dynamics of different biomarkers and presents itself as a promising forage resource.(AU)

O objetivo deste trabalho foi avaliar a resposta metabólica de cordeiros nativos alimentados com feno de capim-tifton 85 (Cynodon dactylon) ou feno de maniçoba (Manihot pseudoglaziovii) associados à palma forrageira (Nopalea cochenillifera Salm Dyck). Foram utilizados 16 cordeiros Morada Nova, com peso inicial médio de 19,36±1,48kg, distribuídos em delineamento de blocos ao acaso, com dois tratamentos e oito repetições. O consumo de matéria seca foi maior nos cordeiros alimentados com feno de maniçoba em comparação ao feno de tifton, enquanto o peso corporal ao abate não foi influenciado pelas dietas. Em relação aos metabólitos sanguíneos, apenas a concentração sérica de ureia foi influenciada, com maior valor observado nos cordeiros que ingeriram a dieta contendo feno de capim-tifton. Quando foi realizada a análise dos biomarcadores sanguíneos nas diferentes coletas quinzenais, foi observado aumento linear nas concentrações sanguíneas de ureia, glicose, frutosamina, fosfatase alcalina e sódio, e efeito quadrático para o potássio sérico. Os demais metabólitos sanguíneos não foram influenciados em função dos dias de coleta. A substituição do feno de tifton 85 por feno de maniçoba influencia positivamente o metabolismo de cordeiros sem causar alterações na dinâmica dos diferentes biomarcadores e se apresenta como um promissor recurso forrageiro.(AU)

Long distance training associated to HIIT protocol does not induce changes in blood biochemical markers in adult marathoners

ABSTRACT Objective: to verify blood markers during a 12-week training protocol and after Sao Paulo Marathon. Methods: Blood samples of 9 male marathoners were collected before (C1) and after (C2) 12-week training protocol, before (C3) and after (C4) marathon. Muscle and liver damage markers (creatine kinase [CK-MM], aspartate aminotransferase [AST], alanine aminotransferase [ALT]), oxidative stress levels (thiobarbituric acid reactive substances [TBARS]) and serum iron concentration were measured. Results: changes were identified comparing moment C4 to other moments for CK-MM and iron. For AST, ALT, and TBARS no differences were identified. Conclusion: strenuous exercises might elicit changes on blood markers, needing follow up strategies to avoid impairments to athletes' performance and health.

RESUMO Objetivo: verificar marcadores sanguíneos durante 12 semanas de treinamento e após a Maratona de São Paulo. Metodologia: amostras de sangue de 9 maratonistas foram coletadas antes (C1) e após (C2) o treinamento de 12 semanas, antes (C3) e após (C4) a maratona. Marcadores sanguíneos e hepáticos (creatina quinase [CK-MM], aspartato aminotransf. [AST], alanina aminotransf. [ALT]), níveis de estresse oxidativo (subst. reativas ácido tiobarbitúrico [TBARS]) e ferro sérico foram analisados. Resultados: Verificaram-se alterações de CK-MM e ferro entre C4 e os outros momentos. Para AST, ALT e TBARS não se encontrou diferenças. Conclusão: exercícios exaustivos podem causar alterações em marcadores sanguíneos, requerendo estratégias de monitoramento para evitar danos ao desempenho e saúde do atleta.

RESUMEN Objetivo: evaluar marcadores sanguíneos durante 12 semanas de entrenamiento y después del Maratón de São Paulo. Metodología: muestras de sangre de 9 maratonistas fueron recogidas antes (C1) y después (C2) el entrenamiento, y antes (C3) y después (C4) a maratón. Se analizaron marcadores sanguíneos y hepáticos (creatina quinasa [CK-MM], aspartato aminotransf. [AST], alanina aminotransf. [ALT]), estrés oxidativo (sustancias reactivas del ácido tiobarbitúrico [TBARS]) y de hierro. Resultados: Se encontraron cambios comparando C4 y otros momentos para CK-MM y hierro. Para AST, ALT y TBARS no se encontraron diferencias. Conclusión: ejercicios extenuantes pueden causar cambios en marcadores sanguíneos, requiriendo estrategias de monitoreo para evitar daños al desempeño y salud del atleta.

Analysis of chronic physiological demand of an annual soccer season / Análise da demanda fisiológica crônica de uma temporada anual de futebol

Abstract Exercise intensity monitoring has been essential for the control and planning of sports training. Thus, the aim of the present study was to assess the chronic physiological demand of soccer players during an annual soccer season using blood biomarkers. Ten professional soccer players (21.2 ± 3.7 years) participated in this study. Blood samples were collected on the day before beginning of preseason (C1); at the end of preseason and beginning of competitive calendar (C2); and at the end of the competitive calendar. Interleukin-6 (IL-6), cortisol, testosterone, testosterone/cortisol ratio, creatine kinase and alpha-actin were evaluated. Statistical analysis was performed by using ANOVA with repeated measures and the post-hoc Tukey's test. Significance level was set at P<0.05. The results showed significant differences in the following situations: testosterone - C1 higher than C2 and C3; cortisol - C3 higher than C2; testosterone/cortisol ratio - C2 higher than C1, and C3 lower than C1 and C2; creatine kinase - C2 and C3 higher than C1; alpha-actin - C3 higher than C1. IL-6 concentrations were not different between C1, C2 and C3. It could be concluded that an annual soccer season imposes high physiological demand for professional players, since relevant changes in blood biomarkers analyzed were observed.

Resumo O monitoramento da intensidade de esforço entre atletas tem se mostrado essencial para o controle e planejamento do treinamento desportivo. Assim, o objetivo do presente estudo foi avaliar por meio de biomarcadores sanguíneos a demanda fisiológica crônica de jogadores de futebol ao longo de uma temporada anual. Dez jogadores profissionais (21,2 ± 3,7 anos) participaram desse estudo. As coletas de sangue foram realizadas no dia anterior ao início da pré-temporada (C1), ao final da pré-temporada e início das competições (C2), e ao final do ano competitivo (C3). Investigou-se as variáveis cortisol, testosterona, relação testosterona/cortisol, creatina quinase, alfa-actina e interleucina 6 (IL-6). Para a análise estatística dos dados utilizou-se ANOVA para medidas repetidas e foi adotado nível de significância de 5%. Os resultados encontrados indicaram diferenças significativas nas seguintes situações: testosterona - C1 maior do que C2 e C3; cortisol - C3 maior do que C2; relação testosterona/cortisol - C2 maior do que C1, e C3 menor do que C1 e C2; creatina quinase - C2 e C3 maior do que C1; alfa-actina - C3 maior do que C1. As concentrações de IL-6 em C1, C2 e C3 não demonstraram diferenças significativas. Pode-se concluir que uma temporada anual de futebol impõe elevada demanda fisiológica entre jogadores profissionais, uma vez que foram observadas alterações relevantes sobre os biomarcadores sanguíneos analisados.