Identification of a ferroptosis-related gene signature predicting recurrence in stage II/III colorectal cancer based on machine learning algorithms.

Background: Colorectal cancer (CRC) is one of the most prevalent cancer types globally. A survival paradox exists due to the inherent heterogeneity in stage II/III CRC tumor biology. Ferroptosis is closely related to the progression of tumors, and ferroptosis-related genes can be used as a novel biomarker in predicting cancer prognosis. Methods: Ferroptosis-related genes were retrieved from the FerrDb and KEGG databases. A total of 1,397 samples were enrolled in our study from nine independent datasets, four of which were integrated as the training dataset to train and construct the model, and validated in the remaining datasets. We developed a machine learning framework with 83 combinations of 10 algorithms based on 10-fold cross-validation (CV) or bootstrap resampling algorithm to identify the most robust and stable model. C-indice and ROC analysis were performed to gauge its predictive accuracy and discrimination capabilities. Survival analysis was conducted followed by univariate and multivariate Cox regression analyses to evaluate the performance of identified signature. Results: The ferroptosis-related gene (FRG) signature was identified by the combination of Lasso and plsRcox and composed of 23 genes. The FRG signature presented better performance than common clinicopathological features (e.g., age and stage), molecular characteristics (e.g., BRAF mutation and microsatellite instability) and several published signatures in predicting the prognosis of the CRC. The signature was further stratified into a high-risk group and low-risk subgroup, where a high FRG signature indicated poor prognosis among all collected datasets. Sensitivity analysis showed the FRG signature remained a significant prognostic factor. Finally, we have developed a nomogram and a decision tree to enhance prognosis evaluation. Conclusion: The FRG signature enabled the accurate selection of high-risk stage II/III CRC population and helped optimize precision treatment to improve their clinical outcomes.

Dose-response association of polycyclic aromatic hydrocarbon with self-reported trouble sleeping in adults: evidence from the National Health and Nutrition Examination Survey.

Previous epidemiological evidence from large population-based studies on the association between polycyclic aromatic hydrocarbons (PAH) exposure and the risk of sleep disorders is inadequate. To comprehensively examine the relationship between independent and combined PAHs and trouble sleeping, we analyzed data from 8194 participants from the National Health and Nutrition Survey (NHANES) cycles. Multivariate adjusted logistic regression and restricted cubic spline models were applied to assess the relationship between PAH exposure and the risk of trouble sleeping. Bayesian kernel machine regression and weighted quantile sum regression models were used to estimate the combined association of urinary PAHs with trouble sleeping. In the single-exposure analyses, compared with the lowest level, the respective adjusted odds ratios (ORs) for trouble sleeping among subjects from the highest quartile were 1.34 (95% CI, 1.15, 1.56), 1.23 (95% CI, 1.05, 1.44), 1.31 (95% CI, 1.11, 1.54), 1.35 (95% CI, 1.15, 1.58), and 1.29 (95% CI, 1.08, 1.53) for 1-hydroxynaphthalene (1-NAP), 2-hydroxynaphthalene (2-NAP), 3-hydroxyfluorene (3-FLU), 2-hydroxyfluorene(2-FLU), and 1-hydroxypyrene(1-PYR). An overall positive correlation between the PAH mixture and trouble sleeping was observed when the mixture was at the 50th percentile or higher. The current study reveals that PAH metabolites (1-NAP, 2-NAP, 3-FLU, 2-FLU, and 1-PYR) may be detrimental to trouble sleeping. PAH mixture exposure was positively associated with trouble sleeping. The results suggested the potential impacts of PAHs and expressed concerns regarding the potential impact of PAHs on health. More intensive research and monitoring of environmental pollutants in the future will contribute to preventing environmental hazards.

Association of educational attainment with esophageal cancer, Barrett's esophagus, and gastroesophageal reflux disease, and the mediating role of modifiable risk factors: A Mendelian randomization study.

Background: Observational studies have reported that educational attainment has been related to the risk of esophageal cancer (EC) and its precancerous lesions. However, the causal relationship remains controversial. We aimed to apply the Mendelian randomization (MR) design to determine the causal associations between genetically predicted educational attainment and EC, Barrett's esophagus (BE), and gastroesophageal reflux disease (GERD), and to explore whether modifiable risk factors play a mediating role. Methods: Using summary statistics from genome-wide association studies (GWASs) based on European ancestry individuals of several years in education (EduYears, primary analysis, n = 293,723), college completion (College, secondary analysis, n = 95,427), EC (n = 420,531), BE (n = 361,194), and GERD (n = 420,531), genetic associations between two education phenotypes and EC, BE, and GERD were tested by two-sample MR analyses. Then, two-step MR mediation analyses were used to assess the proportion of the aforementioned association that might be mediated by body mass index (BMI), major depressive disorder (MDD), smoking, drinking, carbohydrates, fat, and protein intake. Results: Genetically predicted EduYears was negatively associated with the risk of EC, BE, and GERD {odds ratio (OR), 0.64 [95% confidence interval (CI) 0.44-0.94], 0.86 (95% CI, 0.75-0.99), and 0.62 (95%CI, 0.58-0.67)}. EduYears was negatively associated with BMI, MDD, and smoking (range of OR: 0.76-0.84). There were positive associations between BMI, smoking with EC, BE, and GERD, as well as between MDD with GERD (range of OR: 1.08-1.50). For individual mediating effect, BMI and smoking mediated 15.75 and 14.15% of the EduYears-EC association and 15.46 and 16.85% of the EduYears-BE association. BMI, MDD, and smoking mediated 5.23, 4.98, and 4.49% of the EduYears-GERD association. For combined mediation, the aforementioned mediators explained 26.62, 28.38, and 11.48% of the effect of EduYears on EC, BE, and GERD. The mediating effects of drinking and dietary composition were not significant in the effect of education on EC, BE, and GERD. Conclusion: Our study supports that genetically predicted higher educational attainment has a protective effect on EC, BE, and GERD, and is partly mediated by reducing adiposity, smoking, and depression.

Burden of lung cancer along with attributable risk factors in China from 1990 to 2019, and projections until 2030.

OBJECTIVE: This study aimed to identify and project the epidemiological trends and the burden of lung cancer in China. METHODS: We extracted incidence, mortality, disability-adjusted life-years (DALYs) and age-standardized rates of lung cancer in China, between 1990 and 2019, from the Global Burden of Disease Study (2019). The estimated annual percentage change (EAPC) was applied to quantify the trends of lung cancer burden. Furthermore, we used the Bayesian age-period-cohort model to project the incidence and mortality in the next decade. RESULTS: From 1990 to 2019, the estimated national number of lung cancer incident cases increased by 224.0% to 832,920, deaths increased by 195.4% to 757,170 and DALYs increased by 146.1% to 17,128,580, respectively. Meanwhile, the ASIR, ASMR and ASDR showed an upward trend (EAPC of 1.33, 0.94 and 0.42, respectively). The ASIR and ASMR among males were about 2 times more than females, but the increase in ASIR in females (EAPC = 2.24) was more obvious than those in males (EAPC = 0.10) from 2020 to 2030. In China, smoking remained responsible for the highest burden of lung cancer, but the contribution of ambient particulate matter pollution to DALYs increased from 10.6% in 1990 to 22.5% in 2019 in total population. Moreover, we predicted that the number of deaths from lung cancer will increase by 42.7% in China by 2030. CONCLUSION: In China, the burden of lung cancer has been increasing over the past three decades, which highlights more targeted intervention measures are needed to reduce the burden of lung cancer.

Spatiotemporal trends of disease burden of edentulism from 1990 to 2019: A global, regional, and national analysis.

Background: Understanding the spatiotemporal trends in disease burden of edentulism is critical to reducing disease burden of edentulism and deploying medical resources. We assessed the changing patterns of disease burden of edentulism at global, regional, and national levels from 1990 to 2019. Methods: Data on incident cases, prevalent cases, disability-adjusted life years (DALYs), and age-standardized rates (ASRs) of edentulism were extracted from the Global Burden of Disease 2019 Study. We calculated the estimated annual percentage change (EAPC) to quantify spatiotemporal trends in the ASRs of edentulism. Results: In 2019, the number of prevalent cases and DALYs of edentulism were 35.2 and 9.6 million, and the ASPR and ASDR were 43.12/1,000 and 1.18/1,000, with EAPCs of -0.18 [95% confidence interval (CI): -0.28, -0.09] and -0.16[95% CI: -0.26, -0.07] from 1990 to 2019, respectively. Females and the elderly had a higher burden of edentulism. Although the ASPR, ASDR, and ASIR in the high SDI, high-middle SDI, and middle SDI regions showed a decreasing or stable trend, the absolute disease burdens of edentulism in these regions were still high. Although the absolute disease burdens of low SDI and low-middle SDI were low, their ASPR and ASDR showed an upward trend. In countries with high initial disease burden or high SDI, ASPR, ASDR, and ASIR showed stable or declining trends. Conclusion: The absolute disease burden due to edentulism was increasing in many countries and regions. Countries should reduce the disease burden caused by edentulism by adopting measures including the prevention and treatment of dental caries and periodontal disease.

Investigating Causal Associations of Diet-Derived Circulating Antioxidants with the Risk of Digestive System Cancers: A Mendelian Randomization Study.

Molecular mechanisms and observational studies have found that diet-derived antioxidants are associated with digestive system cancers, whereas there is a lack of causal evidence from randomized clinical trials. In this study, we aimed to assess the causality of these associations through a Mendelian randomization (MR) study. Single nucleotide polymorphisms of diet-derived circulating antioxidants (i.e., α- and γ-tocopherol, ascorbate, retinol, ß-carotene, lycopene, and urate), accessed by absolute levels and relative metabolite concentrations, were used as genetic instruments. Summary statistics for digestive system cancers were obtained from the UK Biobank and FinnGen studies. Two-sample MR analyses were performed in each of the two outcome databases, followed by a meta-analysis. The inverse-variance weighted MR was adopted as the primary analysis. Five additional MR methods (likelihood-based MR, MR-Egger, weighted median, penalized weighted median, and MR-PRESSO) and replicate MR analyses for outcomes from different sources were used as sensitivity analyses. Genetically determined antioxidants were not significantly associated with five digestive system cancers, after correcting for multiple tests. However, we found suggestive evidence that absolute ascorbate levels were negatively associated with colon cancer in UK Biobank-the odds ratio (OR) per unit increase in ascorbate was 0.774 (95% confidence interval [CI] 0.608-0.985, p = 0.037), which was consistent with the results in FinnGen, and the combined OR was 0.764 (95% CI 0.623-0.936, p = 0.010). Likewise, higher absolute retinol levels suggestively reduced the pancreatic cancer risk in FinnGen-the OR per 10% unit increase in ln-transformed retinol was 0.705 (95% CI 0.529-0.940, p = 0.017), which was consistent with the results in UK Biobank and the combined OR was 0.747 (95% CI, 0.584-0.955, p = 0.020). Sensitivity analyses verified the above suggestive evidence. Our findings suggest that higher levels of antioxidants are unlikely to be a causal protective factor for most digestive system cancers, except for the suggestive protective effects of ascorbate on colon cancer and of retinol on pancreatic cancer.

Global Trends in Mortality and Burden of Stroke Attributable to Lead Exposure From 1990 to 2019.

Background: Lead exposure is an important risk factor for stroke. However, the latest global spatiotemporal patterns of lead exposure-related stroke burden were unclear. In this study, we assessed this topic. Methods: The data were obtained from the Global Burden of Disease Study (2019). The estimated annual percentage change (EAPC) was estimated to evaluate the temporal trends of the age-standardized mortality and disability-adjusted life years (DALYs) rates (ASMR and ASDR) of stroke attributable to lead exposure. Results: In 2019, the numbers of global stroke deaths and DALYs attributable to lead exposure were 305.27 and 6738.78 thousand, respectively. The corresponding ASMR and ASDR were highest in males, the elderly population, low and middle-income countries, and the intracerebral hemorrhage subtype. From 1990 to 2019, the ASMR and ASDR of global stroke attributable to lead exposure decreased [ASMR: EAPC = -1.34, 95% confidence interval (CI): (-1.57, -1.10); ASDR: EAPC = -1.74, 95% CI: (-1.95, -1.52)], especially in females, the high-income countries, and the subarachnoid hemorrhage subtype. Conclusion: This study emphasizes the importance of continued implementation of lead exposure prevention strategies and improved high-efficiency treatment and stroke acute health care, especially in low and middle-income countries.

Burden of pancreatic cancer along with attributable risk factors in China from 1990 to 2019, and projections until 2030.

OBJECTIVES: Understanding epidemiology trends and patterns of pancreatic cancer in China from 1990 to 2019 and predicting the burden to 2030 will provide foundations for future policies development. METHODS: We collected incidence, mortality, and disability-adjusted life-years (DALYs) data of pancreatic cancer in China from 1990 to 2019 based on the Global Burden of Disease Study 2019. We calculated the estimated annual percentage change (EAPC) to depict the trends of pancreatic cancer burden and predicted the incidence and mortality in the next decade by using a Bayesian age-period-cohort analysis. RESULTS: The number of incident cases sharply increased from 26.77 thousand in 1990 to 114.96 thousand in 2019, the age-standardized incidence rate (ASIR) nearly doubled from 3.17 per 100,000 in 1990 to 5.78 per 100,000 in 2019, with an EAPC of 2.32 (95% confidence interval [CI]: 2.12, 2.51). The mortality and DALYs presented a similar pattern with incidence. The dominant risk factor for pancreatic cancer was smoking, but the contribution of high body-mass index increased from 1990 to 2019. We projected that the incident cases and deaths of pancreatic cancer would increase to 218.79 thousand and 222.97 thousand, respectively, in 2030 with around 2 times growth. CONCLUSIONS: During the past three decades, the incidence, mortality and DALYs of pancreatic cancer gradually increased in China, and the absolute number and rate of pancreatic cancer burden would continue to rise over the next decade. Comprehensive policies and strategies need to be implemented to reduce the incidence and mortality.

Global, regional and national burden of autism spectrum disorder from 1990 to 2019: results from the Global Burden of Disease Study 2019.

AIMS: Autism spectrum disorder (ASD) is a neurodevelopmental condition, with symptoms appearing in the early developmental period. Little is known about its current burden at the global, regional and national levels. This systematic analysis aims to summarise the latest magnitudes and temporal trends of ASD burden, which is essential to facilitate more detailed development of prevention and intervention strategies. METHODS: The data on ASD incidence, prevalence, disability-adjusted life years (DALYs) in 204 countries and territories between 1990 and 2019 came from the Global Burden of Disease Study 2019. The average annual percentage change was calculated to quantify the secular trends in age-standardised rates (ASRs) of ASD burden by region, sex and age. RESULTS: In 2019, there were an estimated 60.38 × 104 [95% uncertainty interval (UI) 50.17-72.01] incident cases of ASD, 283.25 × 105 (95% UI 235.01-338.11) prevalent cases and 43.07 × 105 (95% UI 28.22-62.32) DALYs globally. The ASR of incidence slightly increased by around 0.06% annually over the past three decades, while the ASRs of prevalence and DALYs both remained stable over the past three decades. In 2019, the highest burden of ASD was observed in high-income regions, especially in high-income North America, high-income Asia Pacific and Western Europe, where a significant growth in ASRs was also observed. The ASR of ASD burden in males was around three times that of females, but the gender difference was shrunk with the pronounced increase among females. Of note, among the population aged over 65 years, the burden of ASD presented increasing trends globally. CONCLUSIONS: The global burden of ASD continues to increase and remains a major mental health concern. These substantial heterogeneities in ASD burden worldwide highlight the need for making suitable mental-related policies and providing special social and health services.

The global, regional, and national disease burden of breast cancer attributable to low physical activity from 1990 to 2019: an analysis of the Global Burden of Disease Study 2019.

BACKGROUND: To assess the spatiotemporal variation in female breast cancer attributable to low physical activity (LPA) at a global scale from 1990 to 2019, which is essential to promote physical activity, as well as prevent and control breast cancer. METHODS: The number of deaths and disability-adjusted life years (DALYs), and the corresponding age-standardized rates (ASMR and ASDR) of LPA-related breast cancer in 204 countries and territories from 1990 to 2019 were retrieved from the Global Burden of Disease Study 2019 to measure the related breast cancer burden by age and region. The estimated annual percentage change (EAPC) was calculated to quantify the secular trend in breast cancer burden rates. RESULTS: From 1990 to 2019, globally, both breast cancer deaths and DALYs attributable to LPA nearly doubled, although the corresponding ASMR and ASDR decreased slightly, with EAPC of -0.46 (95% confidence interval: -0.52, -0.40) and -0.44 (95% confidence interval: -0.49, -0.39), respectively. The LPA-related breast cancer burden varied considerably across the world, with the highest-burden rates in Oceania, Tropical Latin America and Caribbean, and the fastest growth in North Africa and Middle East. The ASMR and ASDR showed a logarithmic association with the Socio-demographic Index, and a temporally upward trend in most of 204 countries regardless of the Socio-demographic Index or the ASMR in 1990. CONCLUSIONS: Despite a decline in LPA-related breast cancer burden achieved in many countries during the last 3 decades like Bermuda, Myanmar, USA and China, an increase still occurred in most of 204 countries and territories, such as Solomon Islands, Equatorial Guinea, Japan and India. The findings can bring greater awareness to the importance of promoting physical activity for the local government to control the attributable breast cancer burden.

Spatiotemporal trends in burden of uterine cancer and its attribution to body mass index in 204 countries and territories from 1990 to 2019.

BACKGROUND: Uterine cancer is one of the most common female cancers worldwide, with huge heterogeneity in morbidity and mortality. Although a high body-mass index (BMI) has been linked to uterine cancer, systematic reports about the influence of high BMI and its temporal trends are scarce. METHODS: The annual morbidity, mortality, and disability-adjusted life years (DALYs) of uterine cancer in 204 countries or territories were retrieved from the GBD 2019 study. To reflect trends in disease burden, we also calculated the estimated annual percentage change (EAPC) based on the age-standardized rates of uterine cancer from 1990 to 2019. RESULTS: The global incident cases of uterine cancer increased 2.3 times from 187,190 in 1990 to 435,040 in 2019. Although the age-standardized incidence rate (ASIR) of uterine cancer increased worldwide from 8.67/100,000 in 1990 to 9.99/100,000 in 2019, the age-standardized death rate (ASDR) and DALY rate decreased during the same period. High socio-demographic index (SDI) countries tended to have a higher ASIR than developing regions, and their increasing trend in ASIR was also more pronounced. The disease was rare before 40 years old, but its risk rose sharply among women aged 50-70. A high BMI was linked to more than one-third of deaths from uterine cancer in 2019. CONCLUSIONS: The incidence in developed areas was significantly higher than in developing areas and also increased much more rapidly. Elderly females, especially those with a high BMI, have a higher risk of uterine cancer. Therefore, more health resources may be needed to curb the rising burden in specific populations.

Spatiotemporal trends of the global burden of melanoma in 204 countries and territories from 1990 to 2019: Results from the 2019 global burden of disease study.

This study aimed to estimate the latest magnitudes and temporal trends of melanoma burden at the national, regional, and global levels. The data on melanoma incidence, deaths, and disability-adjusted life-years (DALYs) in 204 countries and territories between 1990 and 2019 came from the Global Burden of Disease 2019 Study. Estimated annual percentage change (EAPC) was calculated to depict the temporal trends and Spearman rank correlation was used to analyze the influential factors of EAPC. From 1990 to 2019, the incident cases of melanoma increased by 170% to 289,950, death increased by 90% to 62,840, and DALYs increased by 67% to 1,707,800 globally. The age-standardized incidence rate (ASIR) of melanoma increased globally by an average of 1.13 [95% confidence interval (CI): 0.93-1.32], while the age-standardized rates of death and DALYs both declined with the EAPC of -0.27 (95% CI: -0.36 to -0.19) and -0.49 (95% CI: -0.57 to -0.41). In 2019, the highest burden of melanoma was observed in Australasia, followed by high-income North America and Europe regions, which all presented an incremental growth in ASIR. The positive association between the EAPC in ASIR and socio-demographic index (SDI) in 2019 (ρ = 0.600, P < 0.001) suggested that countries with higher SDI have experienced a more rapid increase in ASIR of melanoma. In conclusion, the burden of melanoma is increasing globally but differed greatly across the world. Notably, the high burden areas are facing a continuing increase in incidence, which implies more targeted strategies should be taken for reducing the increasing melanoma burden.

Global, regional, and national burden of age-related hearing loss from 1990 to 2019.

The global distribution and temporal trend of age-related hearing loss (ARHL) are unknown, and we aimed to investigate magnitudes and temporal trends of ARHL burden and its influencing factors at the national, regional, and global levels. Based on the information of Global Burden of Disease Study 2019, we calculated the estimated annual percentage change to quantify the global, regional, and national temporal trends of age-standardized rates (ASRs) of ARHL by gender, age, and severity. The number of prevalent cases and disability-adjusted life years (DALYs) of ARHL increased from 751.50 million and 22.01 million in 1990 to 1456.66 million and 40.24 million in 2019, respectively. Except for a few countries such as Niger and Burkina Faso, the age-standardized prevalence rate and age-standardized DALYs rate showed a downward trend in most countries and regions. Mild ARHL accounted for the largest proportion in all ARHL, and only mild ARHL showed an upward trend in ASRs. In most regions, the proportion of ARHL disease burden attributable to occupational noise showed a downward trend in the past 30 years. In 2019, ARHL disease burden attributable to occupational noise declined with the increase of socio-demographic index in countries. Although the ASR of ARHL in most parts of the world is declining, the absolute disease burden of ARHL is still heavy. Understanding the real-time disease burden of ARHL and its temporal trend is of great significance for formulating more effective preventive measures and reducing the ARHL burden.

Global changing trends in incidence and mortality of gastric cancer by age and sex, 1990-2019: Findings from Global Burden of Disease Study.

Background: The global disease burden of gastric cancer (GC) is still heavy. Understanding the patterns and trends of the global GC burden is important for developing precise prevention strategies. Materials and Methods: The data of GC burden were retrieved from the Global Burden of Disease Study (2019). The estimated annual percentage change (EAPC) was calculated to estimate the temporal trends of the age-standardized incidence and mortality rates (ASIR and ASMR) of global GC by age-specific groups (15-49, 50-69, and ≥70 years), sexes, socio-demographic indexes (SDIs), regions, and countries. Results: In 2019, the ASIR and ASMR of global GC increased with age in both sexes, and reached a peak in the older 70 age group. The ASIR and ASMR in males were higher than those in females. From 1990 to 2019, the global number of GC incident cases increased in both sexes in all age-specific groups; while the ASIR of GC decreased, and the most significant decrease was observed in the 50-69 age group [males: EAPC=-1.34, 95% CI: (-1.49, -1.18); females: EAPC= -2.09, 95% CI: (-2.22, -1.96)]. During the study period, downward trends in ASIR of GC were observed in both sexes in most SDI regions, GBD regions, and countries. Similar trends in ASMR of GC were also observed. Conclusion: The global GC incidence and mortality rates decreased from 1990 to 2019 in both sexes, most GBD regions, and most countries. However, the GC burden was still heavy in some GBD regions and countries in special age-specific groups. It is important to formulate and implement tertiary prevention strategies based on the GC burden of age-specific groups in different regions and countries.

Global, regional, and national burden of blindness and vision loss due to common eye diseases along with its attributable risk factors from 1990 to 2019: a systematic analysis from the global burden of disease study 2019.

To map the magnitudes and temporal trends of blindness and vision loss (BVL) due to common eye diseases along with its attributable risk factors at the national, regional, and global levels. The annual burden of BVL in 204 countries and territories was extracted from the Global Burden of Disease Study 2019. The estimated annual percentage change (EAPC) and causes composition change were calculated to quantify the temporal trends of BVL-related disease burden by sex, region, and eye disease. The global disability-adjusted life years (DALYs) of BVL increased from 12.44 million in 1990 to 22.56 million in 2019, with a slightly decreased rate from 3.03 to 2.78 per 1000 population (EAPC = -0.30). About 29.6% of BVL-related DALYs worldwide were caused by cataract, followed by refraction disorders (29.1%), near vision loss (21.7%), other vision loss (13.7%), glaucoma (3.3%), and age-related macular degeneration (2.5%) in 2019. The age-standardized DALYs rates due to each eye disease type in most regions were decreased, especially in countries with high burden and high-middle socio-demographic index. Moreover, the contribution of smoking and air pollution from solid fuels to BVL burden decreased, however, the age-standardized burden of BVL attributed to high body-mass index and high fasting plasma glucose elevated gradually across almost all regions. The temporal trend of BVL burden due to specific eye diseases varies remarkably by region, sex and age. Understanding the real-time patterns of BVL burden is crucial for formulating more effective and targeted prevention and healthcare strategies to decrease the BVL burden.

C16, a novel sinomenine derivatives, promoted macrophage reprogramming toward M2-like phenotype and protected mice from endotoxemia.

Macrophage plays a critical part in host defense, tissue repair, and anti-inflammation; Macrophage reprogramming is responsible for disease development or regression. We aimed to clarify the effect of sinomenine-4-hydroxy-palmitate (C16), on macrophage reprogramming and anti-inflammatory in endotoxemia model. According to a structure modification of SIN (Sinomenine), C16 was found. Then, based on the endotoxin model, the mice liver and kidney toxicity was evaluated and serum cytokines level of IL-6 (Interleukin-6), TNF-α (Tumor necrosis factor-α), and IL-1ß (Interleukin-1ß) were measured by ELISA (Enzyme linked immunosorbent assay). Then, we confirmed the effect of C16 on macrophages reprogramming, we used the flow cytometry to test the effect of C16 on macrophages apoptosis in vitro. Then, iNOS (Inducible nitric oxide synthase), M1-type related cytokines, such as IL-1ß, TNF-α, and M2-type related cytokines, such as Arg-1 (Arginase-1), CD206, Fizz1, and Ym1 was detected, which expressed in ANA-1 and primary peritoneal macrophages. To further explore the molecular mechanism of C16 in reprogramming of macrophages from M1 toward M2 phenotype, the expression of STAT1 (signal transducer and activator of Transcription 1), STAT3, ERK1/2 (extracellular signal regulated kinase1/2), AKT, p38, and its corresponding phosphorylation were determined by western blot. Our results demonstrated that C16 improved the survival rate of LPS- (lipopolysaccharide) challenged mice and decreased the inflammatory cytokines expression; After C16 treatment, the expression of M1 phenotype correlation factors decreased significantly, while the expression of M2 phenotype correlation factors increased significantly at different levels compared with normal group. It indicated that C16 reprogram macrophages phenotype from M1 toward M2 following LPS stimulus. Furthermore, the results also showed that C16 showed anti-inflammatory effect by inhibiting LPS-induced p38, AKT and STAT1 phosphorylation and contributing ERK1/2 activation. C16 promoted macrophage reprogramming toward M2-like phenotype via p-p38/p-AKT or STAT1 signals pathway and C16 might be a valid candidate for inflammatory disease.

Global, regional and national burden of anxiety disorders from 1990 to 2019: results from the Global Burden of Disease Study 2019.

AIMS: Anxiety disorders are widespread across the world. A systematic understanding of the disease burden, temporal trend and risk factors of anxiety disorders provides the essential foundation for targeted public policies on mental health at the national, regional, and global levels. METHODS: The estimation of anxiety disorders in the Global Burden of Disease Study 2019 using systematic review was conducted to describe incidence, prevalence and disability-adjusted life years (DALYs) in 204 countries and regions from 1990 to 2019. We calculated the estimated annual percentage change (EAPC) to quantify the temporal trends in anxiety disorders burden by sex, region and age over the past 30 years and analysed the impact of epidemiological and demographic changes on anxiety disorders. RESULTS: Globally, 45.82 [95% uncertainty interval (UI): 37.14, 55.62] million incident cases of anxiety disorders, 301.39 million (95% UI: 252.63, 356.00) prevalent cases and 28.68 (95% UI: 19.86, 39.32) million DALYs were estimated in 2019. Although the overall age-standardised burden rate of anxiety disorders remained stable over the past three decades, the latest absolute number of anxiety disorders increased by 50% from 1990. We observed huge disparities in both age-standardised burden rate and changing trend of anxiety disorders in sex, country and age. In 2019, 7.07% of the global DALYs due to anxiety disorders were attributable to bullying victimisation, mainly among the population aged 5-39 years, and the proportion increased in almost all countries and territories compared with 1990. CONCLUSION: Anxiety disorder is still the most common mental illness in the world and has a striking impact on the global burden of disease. Controlling potential risk factors, such as bullying, establishing effective mental health knowledge dissemination and diversifying intervention strategies adapted to specific characteristics will reduce the burden of anxiety disorders.

A nomogram for screening esophageal squamous cell carcinoma based on environmental risk factors in a high-incidence area of China: a population-based case-control study.

BACKGROUND: Selection of high-risk subjects for endoscopic screening of esophageal squamous cell carcinoma (ESCC) lacks individual predictive tools based on environmental risk factors. METHODS: We performed a large population-based case-control study of 1418 ESCC cases and 1992 controls in a high-risk area of China. Information on potential risk factors was collected via face-to-face interview using an electronic structured questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models, and predictive nomograms were established accordingly. A weighted analysis was further conducted to introduce age into predictive nomograms due to frequency matching study design. RESULTS: Most cases were usually exposed to 4 to 6 risk factors, but most controls were usually exposed to 3 to 5 risk factors. The AUCs of male and female predictive nomograms were 0.75 (95%CI: 0.72, 0.77) and 0.76 (95%CI: 0.73, 0.79), respectively. The weighted analysis adding age in the predictive model improved the AUC in both men and women (0.81 (95%CI: 0.79, 0.84) and 0.88 (95%CI: 0.85, 0.90), respectively). CONCLUSIONS: An easy-to-use preclinical predictive tool is provided to select candidate population with high ESCC risk for endoscopic screening. Its usefulness needs to be further evaluated in future screening practice.

Changing trends of disease burden of gastric cancer in China from 1990 to 2019 and its predictions: Findings from Global Burden of Disease Study.

OBJECTIVE: China is one of the countries with the heaviest burden of gastric cancer (GC) in the world. Understanding the epidemiological trends and patterns of GC in China can contribute to formulating effective prevention strategies. METHODS: The data on incidence, mortality, and disability-adjusted life-years (DALYs) of GC in China from 1990 to 2019 were obtained from the Global Burden of Disease Study (2019). The estimated annual percentage change (EAPC) was calculated to evaluate the temporal trends of disease burden of GC, and the package Nordpred in the R program was used to perform an age-period-cohort analysis to predict the numbers and rates of incidence and mortality in the next 25 years. RESULTS: The number of incident cases of GC increased from 317.34 thousand in 1990 to 612.82 thousand in 2019, while the age-standardized incidence rate (ASIR) of GC decreased from 37.56 per 100,000 in 1990 to 30.64 per 100,000 in 2019, with an EAPC of -0.41 [95% confidence interval (95% CI): -0.77, -0.06]. Pronounced temporal trends in mortality and DALYs of GC were observed. In the next 25 years, the numbers of new GC cases and deaths are expected to increase to 738.79 thousand and 454.80 thousand, respectively, while the rates of incidence and deaths should steadily decrease. The deaths and DALYs attributable to smoking were different for males and females. CONCLUSIONS: In China, despite the fact that the rates of GC have decreased during the past three decades, the numbers of new GC cases and deaths increased, and will continue to increase in the next 25 years. Additional strategies are needed to reduce the burden of GC, such as screening and early detection, novel treatments, and the prevention of risk factors.

Secular trends in the incidence and survival of all leukemia types in the United States from 1975 to 2017.

Background: Various studies have indicated that the prognosis of leukemia has been improved in recent years, but the secular trends of incidence and long-term survival of all leukemia have not been thoroughly examined. Methods: We estimated the leukemia incidence and 5-year survival rate along with the temporal trends by sex, race, age, and subtype in the United States over the past four decades using Surveillance, Epidemiology, and End Results (SEER) database. Results: The overall incidence of leukemia steadily increased from 12.39/100 000 in 1975 to 14.65/100 000 in 2011, and then began to decline in recent years (13.73/100 000 in 2017), with average annual percent changes (APC) of 0.350 (P<0.001). The 5-year relative survival rate of leukemia patients significantly improved from 33.2% in 1975 to 66.1% in 2012 (APC=1.980, P<0.001). The main subtypes of leukemia, including acute lymphoblastic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, and chronic myeloid leukemia, increased in most age groups; conversely, the incidences of all other subtypes were gradually declined during the monitoring period. The incremental advancement in leukemia prognosis had been achieved in almost all histological subtypes, especially among young patients. Conclusions: Based on SEER data, the leukemia incidence increased gradually over the past decades, and then began to decline in recent years in the United States. The 5-year relative survival rate increased incrementally over time, especially among young patients. However, the huge disparities among different sexes, races, histological subtypes, and age groups, emphasize that precise causes control and innovative treatments need to be developed to reduce the incidence and improve the prognosis, especially among specific populations.