Identification of diagnostic signatures associated with tumor mutation burden in gastric cancer based on TCGA and machine-learning methods / 西安交通大学学报(医学版)

【Objective】 To select and identify miRNA signatures to predict TMB level in gastric cancer based on The Cancer Genome Atlas (TCGA) database and machine learning methods. 【Methods】 MiRNA expression and somatic mutation profiles of gastric cancer (GC) were downloaded from TCGA database. R "limma" package was performed to select differentially expressed miRNAs between high-TMB and low-TMB groups. Two machine learning algorisms, random forest (RF), and Support Vector Machine-Recursive Feature Elimination were utilized to identify miRNAs with the highest discriminative ability. ROC was used to test the predictive ability of these signatures in multiple datasets. Besides, immune cells of different TMB levels were compared by the CIBERSORT method. 【Results】 A total of 56 differentially expressed miRNAs (DE-miRNAs) were filtered. Functional enrichment analysis showed that these DE miRNAs are mainly enriched in signaling pathways related to tumor occurrence and development as well as immunity-related biological processes. The RF and SVM-RFE algorithms jointly identified 10 diagnostic features of miRNAs, among which only hsa-miR-210-3p is considered the most relevant predictive biomarker for TMB classification. The AUC value of hsa-miR-210-3p in the training, testing, and total sets is 0.822, 0.721, and 0.793, respectively, and has been validated in other cancer types. Besides, CIBERSORT analysis suggests differences in immune cell infiltration between high- and low-TMB groups. Meanwhile, there is a significant positive correlation between the expression of immune checkpoint related genes and mismatch repair related genes and hsa-miR-210-3p. 【Conclusion】 This study successfully identified hsa-miR-210-3p as a predictive biomarker for TMB classification, which can effectively predict TMB values in gastric cancer and other cancer patients and may provide some guidance for immunotherapy.

Research Progress of Immunotherapy Biomarkers for Non-small Cell Lung Cancer / 中国肺癌杂志

Lung cancer is one of the most prevalent malignancies with the highest morbidity and mortality rates worldwide. In recent years, with the development of immune-oncology research and several therapeutic antibodies have reach the clinic, many breakthroughs have been made in immunotherapy. The advent of immunotherapy has revolutionized the treatment of NSCLC, but the response and durable clinical benefit are only observed in a small subset of patients. Therefore, strategies to screen the potential beneficial population and improve the efficacy of immunotherapy remain an essential topic. In the current article, the author review the biomarkers that have potential to better predict responders to immunotherapy and to provide ideas for the clinical application of immunotherapy.
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Research progress of PD-1/PD-L1 in small cell lung cancer / 中国肿瘤临床

Small-cell lung cancer (SCLC) has a high degree of malignancy and is characterized by strong invasiveness, rapid growth, and early metastasis. SCLC is sensitive to initial treatment with chemotherapy and radiotherapy, but it can easily relapse and has a poor prognosis. Both programmed death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) antagonists activate the immune response of tumor cells by activating T cells, and have shown exciting curative effects in clinical studies of SCLC, thereby becoming powerful po-tential agents to treat SCLC in the future. This article aims to illustrate the progress of PD-1/PD-L1 inhibitors in the treatment of SCLC, as well as the role of PD-L1 expression and tumor mutation burden (TMB) as a biomarker in SCLC.

Determination of the activity of cytochrome C by the chromogenic substrate method / 中国生化药物杂志

Objective To establish the chromogenic substrate method to determine the activity of cytochrome C.Methods Used TMB as the chromogenic substrate, reacted at 37 ℃ for 15 min, generated the yellow products, and detected the absorbance at 450 nm.The experimental design method is the 4 ×4 parallel line quantitative analysis.ResuIts The activities of cytochrome C injection samples have been determined.The linear regression equation was Y=0.9875 X -1.0221,R2 =0.9996.The accuracy and repeatability were 1.1 % and 3.6 %.ConcIusion The chromogenic substrate method was simple operation, sensitive and can be used to determine the activity of cytochrome C.

Hepatitis B Seroconversion after Vaccination in Infants in Rural and Urban Areas of Rawalpindi, Pakistan.

Purpose: This study was designed to evaluate the immunogenicity of hepatitis B vaccine in infants of rural and urban Pakistan and to find out the vaccine efficacy. Methods: A sample of 400 subjects was taken by simple random method from the rural and urban areas (200 from Rural and 200 from urban areas) of Rawalpindi District Pakistan. The serum samples were analyzed by Enzyme Linked Immunosorbant assay (ELISA) for the quantitative determination of antiHBs antibodies. Results: As 88 (22%) infants out of the total 400 were found to be seropositive at baseline. The post vaccination results showed that about 15 (7.53%) of infants had inadequate levels of antibodies (i.e. <10 IU/L). Overall 92.46% infants showed a positive response to the vaccine. The females showed higher titers of antiHBs against vaccination as compared to that of males. Infants of urban areas showed higher titers as compared to that of rural areas. Conclusion: Our results reinforces that the Hepatitis B vaccine has a good tolerability and is highly immunogenic among infants. It is recommended that serosurvey of HBsAg and vaccine coverage at country level should be done.

Taxa metabólica basal de homens residentes na cidade de Goiânia / Basal energy expenditure in men living in Goiânia

INTRODUÇÃO: A Taxa Metabólica Basal (TMB) é a quantidade de energia necessária para o corpo humano manter os processos fisiológicos normais e a homeostase. Atualmente, a TMB é calculada a partir de equações baseadas na população norte-americana e/ou europeia. OBJETIVO: Comparar as equações de Harris-Benedict, Food and Agriculture Organization e Institute of Medicine com a calorimetria indireta em indivíduos do sexo masculino residentes na cidade de Goiânia. MÉTODOS: A determinação da TMB foi feita pela análise direta de gases, utilizando o analisador VO2000. Foram avaliados 44 voluntários do sexo masculino, com média de idade 29,8 anos (Desvio padrão - DP = 6,21), estatura 1,79 m (DP = 0,06), peso 77,79 kg (DP = 8,49), IMC 24,30 kg/m2 (DP = 1,96), gordura corporal 15,84% (DP = 4,49), circunferência da cintura 80,48 cm (DP = 5,89). RESULTADOS: Foi observada diferença significante (p < 0,05) para os valores da TMB estimada pelas equações de Harris-Benedict (1.824,7, DP = 138,2 kcal/dia) e Food and Agriculture Organization (1.821,8, DP = 115,4 kcal/dia), quando comparado ao valor obtido pela calorimetria indireta (1.709,8, DP = 329,7 kcal/dia). Esse valor não foi significantemente diferente do obtido pela equação do Institute of Medicine (1.791, DP = 329 kcal/dia). CONCLUSÃO: As equações Harris-Benedict e Food and Agriculture Organization podem superestimar a TMB de homens jovens, sadios, com características semelhantes as do presente estudo. As equações do Institute of Medicine, por sua vez, resultam em valores estimados de TMB mais próximos aos mensurados.

INTRODUCTION: Baseline Energy Expenditure (BEE) is the amount of energy necessary to the human body to keep the normal physiological processes and homeostasis. Currently, the BEE is calculated from equations based on the North American and/or European population. OBJECTIVE: To compare the equations of Harris-Benedict, Food and Agriculture Organization and Institute of Medicine with the indirect calorimeter in men living in Goiânia. METHODS: Forty- four male volunteers, average age of 29.80, Standart Deviation - SD = 6.21 years, stature 1.79, SD = 0.06m, weight 77.79, SD = 8.49 kg, BMI 24.30, SD = 1.96 kg/m2, body fat 15.84, SD = 4.49%, waist circumference 80.48, SD = 5.89 cm, were evaluated. BEE was determined by direct gas analyses using the gas analyzer VO2000. RESULTS: There was significant difference (p < 0.05) for the BEE estimated by the Harris-Benedict (1824.66 ± 138.25 kcal/day) and Food and Agriculture Organization (1821.77, SD = 115.39 kcal/day) equations when compared to the BEE acquired by the indirect calorimeter (1709.81, SD = 329.75 kcal/day). The BEE estimated by the equation IOM/2005 (1791.81, SD = 329.74) did not present significant difference when compared to the measured BEE. CONCLUSION: The Food and Agriculture Organization and Harris-Benedict equations can overestimate the BEE of healthy young men with similar characteristics to those reported in this work.

Calcium Ions are Involved in Modulation of Melittin-induced Nociception in Rat: II. Effect of Calcium Chelator

Melittin, a major component of bee venom, produces a sustained decrease in mechanical threshold, and an increase in spontaneous flinchings and paw thickness, which are characteristics similar to those induced by whole bee venom. Melittin-induced nociception has been known to be modulated by the changes in the activity of excitatory amino acid receptors, voltage-dependent calcium channels, cyclooxygenase and serotonin receptors. The present study was undertaken to investigate the role of calcium chelators (TMB-8 & Quin 2) in melittin-induced nociceptive responses. Changes of mechanical threshold and spontaneous flinching behaviors were measured at a given time point following intraplantar injection of melittin (30microgram/paw). Intrathecal or intraplantar pre-administration and intrathecal post-treatment of TMB-8 and Quin 2 significantly prevented the melittin-induced reduction of mechanical threshold, and intraplantar or intrathecal pre-treatment of TMB-8 and Quin 2 suppressed melittin-induced flinching behaviors. These results indicate that calcium ion in the spinal dorsal horn neurons and peripheral nerves plays an important role in the production and maintenance of mechanical allodynia and spontaneous pain by melittin.

Effects of TMB-8 on cerebral blood flow of focal cerebral ischemia in rats / 临床神经病学杂志

Objective To study the effect of TMB 8 on cerebral blood flow(CBF) of focal cerebral ischemia in the rats.Methods CBF in the middle cerebral artery occlusion after the middle cerebral artery occlusion was measured by a Laser Doppler Flowmeter. TMB 8 was administered 30 min before occlusion and 20 min after occlusion respectively.Results CBF was reduced quickly. TMB 8 0.5,1,2 mg/kg was administered 30 min before occlusion of the middle cerebral artery.The dosage inhibited the reduction of CBF,20 min after occlusion, CBF was increased by TMB 8 1 mg/kg significantly.Conclusion TMB 8 could prevent and treat the reduction of CBF in focal cerebral ischemia of MCAO in the rats,and improved the supply of blood in ischemic area.