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Objective:To explore the predictive value of peripheral blood cytokine models on organ functional impairment after chimeric antigen receptor T(CAR-T) cell therapy in children with B-lineage lymphocytic leukemia.Methods:The clinical data of 44 children with acute B-lineage lymphoblastic leukemia who received CAR-T cell therapy at Children′s Hospital of Soochow University from September 2018 to October 2020 were retrospectively analyzed.Peripheral blood cytokines, including interleukin(IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-α, interferon(IFN)-γ and IL-17A, were measured daily for 14 days after receiving CAR-T cell therapy.The trend of peripheral blood cytokine levels was analyzed at the endpoint of organ function recovery or death within 14 days after CAR-T cell treatment.Receiver operating characteristic curve was used to establish a mathematical prediction model to predict the occurrence of organ damage in the children.Results:Of the 44 children, 31 cases were boys and 13 cases were girls, with a median age of 7.96 (5.19, 11.48)years.Cytokine release syndrome(CRS) response occurred in 95.5% (42/44) children, with 88.1% (37/42) had a grade 1-3 CRS response, and 16.7% (7/42) had a severe grade 4-5 CRS response.Using IL-6>3 892.95 pg/mL as cut-off value, the area under the curve(AUC) for predicting acute respiratory failure was 0.818, with a sensitivity of 0.8 and a specificity of 0.735, while combining IFN-γ>414.4 pg/mL, IL-6>3 892.95 pg/mL and IL-2>27.05 pg/mL were the three cut-off values, with an AUC of 0.741, sensitivity of 0.6 and specificity of 0.912 for predicting acute respiratory failure. Using IFN-γ>1 699.5 pg/mL as cut-off value, the AUC for predicting shock was 0.908, with a sensitivity of 0.722 and a specificity of 1.With IL-6>4 607.3 pg/mL as cut-off value, the AUC for predicting liver injury was 0.964, with a sensitivity of 1 and a specificity of 0.906, while combining both IL-6>4 607.3 pg/mL and IFN-γ>1 446.2 pg/mL as cut-off values, the AUC for predicting liver injury was 0.977, with a sensitivity of 1 and a specificity of 0.906.Combining both IL-6>6 972.2 pg/mL and IFN-γ>3 981.5 pg/mL predicted a positive predictive value of 62.5% and a negative predictive value of 94.4% for grade 4-5 CRS response, with an AUC of 0.846, a predictive sensitivity of 0.714 and a specificity of 0.838, and all children had a combination of two or more organ function injuries.Conclusion:The combination of IL-6 and IFN-γ can effectively predict the incidence of liver injury and cytokine release syndrome.The combination of peripheral blood cytokines IFN-γ, IL-6 and IL-2 can be used to predict the incidence of acute respiratory failure after the treatment of CAR-T cells in children with acute B-lineage lymphoblastic leukaemia.IFN-γ single index can be used to predict the incidence of shock.The combination of IL-6 and IFN-γ can be used to predict the incidence of liver injury and the severity of CRS.
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Objective To study the genotypes, epidemiological characteristics and homology of Noroviruses (NoV) circulating in Shenzhen in the winter of 2017. Methods RT-PCR was performed using Nov-specific primers after extracting viral genome from 313 fecal samples. Positive RT-PCR products were then sequenced. Phylogenetic trees were constructed based upon the gene sequences of isolated and reference NoV strains using Mega 4. 1 and Clustal W software. Results There were 26 NoV-positive samples and all belonged to G Ⅱ. 4 subtype. These strains shared high homologies with G Ⅱ. 4 ( KY407156), G Ⅱ. 4 (KY580757) and GⅡ. 4 (KX372682). Phylogenetic analysis also suggested that 88. 46％ of them had a lower homology with the NoV strains isolated in the same area in recent years and 46. 15％ were different from the epidemic strains in other provinces of China. Conclusion NoV GⅡ. 4 was the epidemic strain in Shenzhen during the winter of 2017. More attention should be paid to it from the local public health authori-ties considering its owned characteristics in epidemic and homology.
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Globally, individuals with chronic diseases now consume over 80% of all healthcare resources. Set against this depressing projection is decades of epidemiologic work demonstrating that 80%-90% of cardiovascular disease can be prevented via lifestyle and dietary interventions. How can we reconcile such contrasting views toward the future of cardiovascular health in human populations? Herein, we review available sources of evidence that can be used to answer these challenging questions of how and why. In particular, we submit that analytical framework incorporating the 6P (prediction, precision, personalization, prevention, population, and policy)-3G (good food, good environment, and good behavior)-4I (interpretation, integration, implementation, and innovation) will allow us to focus resource towards the development of multi-level approaches for the betterment of population