The global burden of childhood and adolescent leukaemia and attributable risk factors: An analysis of the Global Burden of Disease Study 2019.

Background: Aim of this study is to estimate the burden of leukaemia in children and adolescents, as well as the socio-demographic index (SDI), for 21 regions around the world from 1990 to 2019. Methods: We also conducted an analysis of the Joinpoint model to estimate the time trend of childhood and adolescent leukaemia incidence, death, and disability-adjusted life years (DALYs) rate and age-standardised rates (ASR) of leukaemia. Results: According to our analysis, the middle SDI experienced the highest decrease in incidence rate between 1990 and 2019, with an average annual percent change (AAPC) of -2.8 (95% confidence interval (CI) = -3.0, -2.6, P < 0.05). We showed that DALYs of children leukaemia is 155.98 (95% uncertainty interval (UI) = 127.18, 182.64) for global male, however, global female leukaemia DALYs is 117.65 (95% UI = 102.07, 132.70). Conclusions: Despite the observed decline in the incidence, mortality, and DALYs of leukaemia over the last three decades, the burden of childhood and adolescent leukaemia remains high, particularly in areas with lower SDI.

Chrysin inhibits ferroptosis of cerebral ischemia/reperfusion injury via regulating HIF-1α/CP loop.

Chrysin is a natural flavonoid with powerful neuroprotective capacity. Cerebral ischemia/reperfusion injury (CIRI) is associated with oxidative stress and ferroptosis. Hypoxia-inducible factor 1α (HIF-1α) and ceruloplasmin (CP) are the critical targets for oxidation reactions and iron transport. But the regulatory mechanism between them is still unclear. Transient middle cerebral artery occlusion (tMCAO) model in rats and oxygen and glucose deprivation/re-oxygenation (OGD/R) model in PC12 cells were applied. Pathological tissue staining and biochemical kit were used to evaluate the effect of chrysin. The relationship between HIF-1α and CP was verified by transcriptomics, qRT-PCR and Western blot. In CIRI, HIF-1α/CP loop was discovered to be the regulatory pathway of ferroptosis. CIRI led to activation and nuclear translocation of HIF-1α, which promoted CP transcription and translation, and downstream ferroptosis. Inhibition of HIF-1α had opposite effect on CP and ferroptosis regulation. Overexpression of CP increased the expression of HIF-1α, nevertheless, inhibited the nuclear translocation of HIF-1α and alleviated CIRI. Silencing CP promoted HIF-1α elevation in nucleus and aggravated CIRI. Mechanistically, chrysin restrained HIF-1α nuclear translocation, thereby inhibiting CP transcription and translation, which in turn reduced downstream HIF-1α expression and mitigated ferroptosis in CIRI. Our results highlight chrysin restrains ferroptosis in CIRI through HIF-1α/CP loop.

Health related quality of life in pediatric hematological malignancies patients and survivors: A meta-analysis of comparative studies.

BACKGROUND: Pediatric patients with hematologic malignancies (HM) and survivors are at high risk for numerous negative effects including decreased health-related quality of life (HRQOL). In order to understand the association between HM and QOL, we conducted this meta-analysis to systematically compare QOL between pediatric HM patients and survivors and controls. METHOD: The PubMed, EMBASE, Web of Science and the Cochrane Library databases were systematically searched. Data were analyzed using the random-effects model. RESULTS: Of 6586 unique articles identified, 30 were included in this meta-analysis. Studies described 12 different HRQOL tools. Different QOL measures varied in their association with quality of life. When compared with Non-HM group, the Pediatric Quality of Life Inventory (PedsQL) has a moderate effect size (standard mean difference, SMD = 0.50, 95% CI: 0.32, 0.68; P < 0.001). When compared with health controls, it has a large effect size (SMD = -1.00, 95% CI: -1.47, -0.53; P < 0.001). In addition, Health utilities index mark (HUI), and the Pediatric Oncology Quality of Life Scale (POQOLS) have a large (SMD = -0.81, 95% CI: -1.29, -0.33; P = 0.001) and a small (SMD = -0.10, 95% CI: -0.42, 0.22; P = 0.534) effect sizes when comparing overall controls. CONCLUSION: Pediatric HM patients and survivors had lower QOL compared with healthy controls and higher QOL compared with Non-HM controls in most domains. Considering the negative impact of poor QOL on daily life and functional outcomes, future research should focus on proposing effective measures to improve QOL of this population.