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.

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.

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.

Association of cooking fuel use with risk of cancer and all-cause mortality among Chinese elderly people: a prospective cohort study.

When cooking with biomass and fossil fuels, their incomplete burning can lead to air pollution, which can trigger pernicious effects on people's health, especially among the elderly, who are more vulnerable to toxic and harmful environmental damage. This study explored the association between different cooking fuel types and the risk of cancer and all-cause mortality among seniors constructing Cox regression models. Data were obtained by linking waves of 6, 7, and 8 of the Chinese Longitudinal Healthy Longevity Survey, which included a total of 7269 participants who were 65 years old and over. Cooking fuels were categorized as either biomass, fossil, or clean fuels. And the effects of switching cooking fuels on death risk were also investigated using Cox regression models. The results indicate that, compared with the users of clean fuels, individuals using biomass or fossil fuels were at a greater death risk for cancer [HR (95% CI): biomass, 1.13 (1.05-1.20); fossil, 1.16 (1.06-1.25)] and all causes [HR (95% CI): biomass, 1.29 (1.16-1.42); fossil, 1.32 (1.22-1.50)]. Furthermore, compared with sustained users of biomass fuels, individuals converting from biomass to clean fuels significantly reduced death risk for cancer [HR (95% CI): 0.81 (0.72-0.95)] and all causes [HR (95% CI): 0.76 (0.64-0.93)]. Similarly, all-cause death risk [HR (95% CI): 0.77 (0.62-0.93)] was noticeably reduced among these participants converting from fossil to clean fuels than persistent users of fossil fuels. Subgroup analyses revealed that males had a greater cancer and all-cause death risk when exposed to unclean fuels. These findings can inform the development of policies and the implementation of measures related to cooking fuel use to promote the health of older people and reduce the burden of disease on society.

Secular trends in the mortality of gastrointestinal cancers across China, Japan, the US, and India: An age-period-cohort, Joinpoint analyses, and Holt forecasts.

Background: Colon cancer, esophageal cancer, and stomach cancer are the common causes of morbidity and mortality in China, Japan, the US., and India. The current study aims to assess and compare secular trends of the mortality of gastrointestinal cancers during the period, 1990-2017 in age-specific, time period, and birth cohort effects. Method: We used the Joinpoint model to collect age-standardized mortality rates (ASMRs) for four countries. We designed an age-period-cohort (APC) analysis to estimate the independent effects on the mortality of three types of cancers. Result: The Joinpoint model shows that in addition to the death rate of esophageal cancer in Japan, the ASMR of esophageal cancer and stomach cancer in other countries declined rapidly. The APC analysis presented a similar pattern of age effect between four countries for colon cancer and stomach cancer, which increased from 20 to 89 age groups. Differently, the period effect rapidly increased for esophageal cancer and stomach cancer in the US, and the period effect in China presented a declining volatility, showing its highest value in 2007. In future, highest mortality trends are likely to occur in China. Conclusion: Therefore, the obvious increase in colon cancer recommended that earlier tactics must be performed to reduce mortality from specific causes from 2018 to 2027.

Association of all Cause and Cause-Specific Mortality With Hearing Loss Among US Adults: A Secondary Analysis Study.

Objectives: Previous research revealed the relationship between hearing loss (HL) and all cause mortality. The aim of this study was to determine the association between HL and all causes and cause-specific mortality based on US adults. Methods: Data were obtained by linking National Health Interview Survey (NHIS) (2004-2013) with linkage to a mortality database to 31 December 2015. HL were categorized into four groups: good hearing, a little hearing difficulty, a lot of hearing difficulty, profoundly deaf. The relationship between HL and mortality risk was analyzed using Cox proportional hazards regression model. Results: Compared with the reference group (Good), those who had light or moderate hearing problems were at an increased risk of mortality for all causes (A little trouble-HR: 1.17; 95% confidence interval [CI]: 1.13 to 1.20; A lot of trouble-HR: 1.45; 95% CI: 1.40-1.51); deaf-HR: 1.54; 95% CI: 1.38-1.73) respectively. Conclusion: In addition, those in the deaf category have the highest risk of death from all causes and cause-specific cancer. More older adults are associated with an increased risk of all-cause mortality in American adults.

Liquid-phase scanning electron microscopy for single membrane protein imaging.

Liquid-phase electron microscopy is highly desirable for observing biological samples in their native liquid state at high resolution. We developed liquid imaging approaches for biological cells using scanning electron microscopy. Novel approaches included scanning transmission electron imaging using a liquid-cell apparatus (LC-STEM), as well as correlative cathodoluminescence and electron microscopy (CCLEM) imaging. LC-STEM enabled imaging at a ∼2 nm resolution and excellent contrast for the precise recognition of localization, distribution, and configuration of individually labeled membrane proteins on the native cells in solution. CCLEM improved the resolution of fluorescent images down to 10 nm. Liquid SEM technologies will bring unique and wide applications to the study of the structure and function of cells and membrane proteins in their near-native states at the monomolecular level.

Trend dynamics of thyroid cancer incidence among China and the U.S. adult population from 1990 to 2017: a joinpoint and age-period-cohort analysis.

BACKGROUND: Thyroid cancer (TC) is the most common malignant disease of the endocrine system. Based on the previously published reports, the incidence of TC has been increasing in the past 25 years, and the reason for the increase is not yet clear. The present study aims to reveal the long-term trends and age-period-cohort effects for the incidence of TC in China and the U.S. from 1990 to 2017. METHODS: We examined the trends of TC incidence and the average annual percentage change (AAPC) of rate using the Joinpoint regression analysis in the two countries, for the different genders (men/women) in the Global Burden of Disease (GBD 2017). We further used an age-period-cohort model to analyze age-period-cohort effects on TC incidence. RESULTS: The ASIR of China increased markedly with AAPC of 4.5% (95% confidence interval (CI): 4.0, 5.0%) and 1.8% (1.6, 2.0%) for men and women during 1990-2017. The ASIR of the U. S increased by 1.4% (1.0, 1.8%) and 1.3% (0.9, 1.7%) for men and women from 1990 to 2017.TC increased with the age and period. Aging was one of the most influential factors of TC in China. The age effect increased markedly in the U.S. compared with China. The period effect showed an increase in China while that tended to grow steadily during 1990-2017 in the U.S. The cohort effect peaked in 1963-1967 birth cohorts for men and women in China and declined consistently in the birth cohort in the U.S. CONCLUSION: From 1990 to 2017, due to ionizing radiation and over-diagnosis, age-standardized TC incidence rates in both genders rose in China and the U.S. The standardized incidence rate of women is higher than that of men. It is necessary to provide women with reasonable prevention and protection measures for TC. We need to apply for health services and screening to reduce ionizing radiation.

A Long-Term Trend Study of Tuberculosis Incidence in China, India and United States 1992-2017: A Joinpoint and Age-Period-Cohort Analysis.

Tuberculosis (TB) is one of the major infectious diseases with the largest number of morbidity and mortality. Based on the comparison of high and low burden countries of tuberculosis in China, India and the United States, the influence of age-period-cohort on the incidence of tuberculosis in three countries from 1992 to 2017 was studied based on the Global burden of Disease Study 2017. We studied the trends using Joinpoint regression in the age-standardized incidence rate (ASIR). The regression model showed a significant decreasing behavior in China, India and the United States between 1992 and 2017. Here, we analyzed the tuberculosis incidence trends in China, India, as well as the United States and distinguished age, period and cohort effects by using age-period-cohort (APC) model. We found that the relative risks (RRs) of tuberculosis in China and India have similar trends, but the United States was found different. The period effect showed that the incidence of the three countries as a whole declines with time. The incidence of tuberculosis had increased in most age group. The older the age, the higher the risk of TB incidence. The net age effect in China and India showed a negative trend, while the cohort effect decreased from the earlier birth cohort to the recent birth cohort. Aging may lead to a continuous increase in the incidence of tuberculosis. It is related to the aging of the population and the relative decline of the immune function in the elderly. This should be timely population intervention or vaccine measures, especially for the elderly. The net cohort effect in the United States showed an unfavorable trend, mainly due to rising smoking rates and the emergence of an economic crisis. Reducing tobacco consumption can effectively reduce the incidence.