Changing epidemiology of inflammatory bowel disease in children and adolescents.

BACKGROUND: The incidence of inflammatory bowel disease (IBD) is rising worldwide, but epidemiological data on children and adolescents are lacking. Understanding the global burden of IBD among children and adolescents is essential for global standardization of methodology and treatment options. METHODS: This is a cross-sectional study based on aggregated data. We estimated the prevalence and incidence of IBD in children and adolescents between 1990 and 2019 according to the Global Burden of Disease Study 2019 (GBD 2019). Age-standardized rates (ASRs) and estimated annual percentage changes (EAPCs) were used to compare the burden and trends between different regions and countries. RESULTS: In 2019, there were 25,659 new cases and 88,829 prevalent cases of IBD among children and adolescents globally, representing an increase of 22.8% and 18.5%, respectively, compared to 1990. Over the past 30 years, the incidence and prevalence of IBD among children and adolescents have been highest in high SDI regions, with the most significant increases in East Asia and high-income Asia Pacific. At the age level, incidence and prevalence were significantly higher in the 15-19-year-old age group, while the < 5-year-old group showed the most significant increase in incidence and prevalence. CONCLUSION: The incidence of IBD in children and adolescents is significantly on the rise in some countries and regions, and IBD will remain an important public health issue with extensive healthcare and economic costs in the future. The reported IBD burden in children and adolescents at the global, regional, and national levels will assist in the development of more precise health policies.

Epidemiological study of pediatric nutritional deficiencies: an analysis from the global burden of disease study 2019.

BACKGROUND: Nutritional deficiencies (ND) continue to threaten the lives of millions of people around the world, with children being the worst hit. Nevertheless, no systematic study of the epidemiological features of child ND has been conducted so far. Therefore, we aimed to comprehensively assess the burden of pediatric ND. METHODS: We analyzed data on pediatric ND between 1990 and 2019 from the Global Burden of Disease study (GBD) 2019 at the global, regional, and national levels. In addition, joinpoint regression models were used to assess temporal trends. RESULTS: In 2019, the number of prevalent cases of childhood malnutrition increased to 435,071,628 globally. The global age-standardized incidence, prevalence, and DALY rates showed an increasing trend between 1990 and 2019. Meanwhile, the burden of child malnutrition was negatively correlated with sociodemographic index (SDI). Asia and Africa still carried the heaviest burden. The burden and trends of child malnutrition varied considerably across countries and regions. At the age level, we found that malnutrition was significantly more prevalent among children < 5 years of age. CONCLUSION: Pediatric ND remains a major public health challenge, especially in areas with low SDI. Therefore, primary healthcare services in developing countries should be improved, and effective measures, such as enhanced pre-school education, strengthened nutritional support, and early and aggressive treatment, need to be developed.

Global, regional, and national burden of intestinal obstruction from 1990 to 2019: an analysis from the Global Burden of Disease Study 2019.

BACKGROUND: Intestinal obstruction (IO) is a common surgical acute abdominal condition that places a significant burden on modern health systems. Unfortunately, the global burden and trends of IO remain unknown. Therefore, this study aimed to comprehensively assess its long-term trends and epidemiological features, which will help policymakers to formulate appropriate health policies. METHODS: We conducted an ecological study using data from the Global Burden of Disease Study (GBD) 2019. Data on IO were analyzed by sex, age, year, sociodemographic index (SDI), and location according to GBD 2019. In addition, joinpoint regression analysis was used to assess temporal trends. Age-period-cohort analysis (APC Analysis) was conducted to evaluate age, period, and birth cohort effects on IO incidence and mortality risk. RESULTS: Globally, the prevalent and incident cases increased by 56.91% and 86.67% from 1990 to 2019, respectively. Joinpoint regression analysis showed that age-standardized incidence rate (ASIR) and age-standardized prevalence rate (ASPR) increased, but age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life year (DALY) rate decreased over the past three decades. The age effect demonstrated that older people have a higher risk of morbidity and mortality. The period effect of incidence and mortality showed an upward trend from 1990 to 2019. Cohort effect revealed that the incidence and death risk peaked in the earlier-born cohort and was lower in the more recent-born cohort. Notably, we found that the burden of IO was higher in males than in females throughout the study period. There are huge disparities in IO burden among countries. CONCLUSION: Globally, the reported incidence and prevalence of IO increased from 1990 to 2019. The burden of IO differed markedly by age, sex, country, and region. Middle-aged and elderly people over 50 years old were at high risk. Given the ageing population, the burden of IO will be a major public health challenge. Thus, there is a strong necessity to strengthen prevention and early intervention in the at-risk population.

Icariin alleviates ferroptosis-related atherosclerosis by promoting autophagy in xo-LDL-induced vascular endothelial cell injury and atherosclerotic mice.

Vascular endothelial cells (VECs) are located between the blood plasma and the vascular tissue, and the ferroptosis (iron-dependent programmed cell death) of VECs can lead to a range of cardiovascular diseases. Icariin is the main active ingredient of Epimedium brevicornum Maxim., which can improve endothelial cell dysfunction. In the present study, the protective effects of icariin on oxidised low-density lipoprotein (ox-LDL)-treated VECs and high-fat diet-fed Apolipoprotein E-deficient mice were investigated. Inflammatory fibrosis in tissues and inflammatory factors in serum and cell supernatants were detected, and mitochondrial membrane potential and the expression levels of ferroptosis-associated proteins were also detected. The results revealed that icariin reduced the endothelial atherosclerotic plaque area and collagen fibres in aortic sinus tissue, and increased the viability and mitochondrial membrane potential, whereas it reduced the reactive oxygen species levels of VECs. The nucleation of transcription factor EB (TFEB) and subsequent autophagy were negatively associated with ferroptosis in endothelial cells, and the more prominent the autophagy, the lower the levels of ferroptosis. Furthermore, by co-treating the cells with icariin and the two autophagy inhibitors, Bafilomycin A1 (blocking autophagosome and lysosome fusion) and 3-methyladenine (blocking autophagosome formation), respectively, the promoting effects of icariin on autophagy were found to be mediated through the process of autophagosome-lysosome fusion. In in vivo experiments, icariin reduced ferroptosis, alleviated atherosclerotic lesions and increased the rate of TFEB nucleation. Additionally, it was found that ARG304, THR308 and GLN311 were the optimal binding sites for the interaction between icariin and TFEB. Taken together, these results suggest that the fusion of autophagosomes and lysosomes promoted by icarrin enhances autophagy and thus reduces ferroptosis. Therefore, icariin may be a potential candidate for the prevention of ferroptosis of VECs and, thus, for the treatment of cardiovascular diseases.

Salvianolic Acid B Inhibits Ferroptosis and Apoptosis during Myocardial Ischemia/Reperfusion Injury via Decreasing the Ubiquitin-Proteasome Degradation of GPX4 and the ROS-JNK/MAPK Pathways.

Myocardial ischemia/reperfusion injury (MIRI) is related to ferroptosis and apoptosis elicited by reactive oxygen species (ROS). In this research, we investigated the protective effect of salvianolic acid B (SAB) as a natural antioxidant on ferroptosis and apoptosis in the MIRI process, and discussed the protective mechanism inhibiting ubiquitin-proteasome degradation of glutathione peroxidase 4 (GPX4) and the c-Jun N-terminal kinases (JNK) apoptosis signal pathway. We observed that ferroptosis and apoptosis occurred in the MIRI rat model in vivo and the H9c2 cardiomyocyte hypoxia/reoxygenation (H/R) damage model in vitro. SAB can alleviate tissue damage related to ROS, ferroptosis and apoptosis. Ubiquitin-proteasome degradation of GPX4 occurred in H/R models, and SAB reduced the ubiquitin-proteasome degradation of GPX4. SAB downregulates JNK phosphorylation and the expression of BCL2-Associated X (Bax)/B-cell lymphoma-2 (Bcl-2) and Caspase-3 to inhibit apoptosis. The role of GPX4 in the cardioprotection of SAB was further verified by the elimination effect of the GPX4 inhibitor RAS-selective lethal 3 (RSL3). This research shows that SAB may be used as a myocardial protective agent against oxidative stress, ferroptosis and apoptosis, and has potential clinical application prospects.

Qixian granule inhibits ferroptosis in vascular endothelial cells by modulating TRPML1 in the lysosome to prevent postmenopausal atherosclerosis.

ETHNOPHARMACOLOGICAL RELEVANCE: QiXian Granule (QXG) is an integrated traditional Chinese medicine formula used to treat postmenopausal atherosclerotic (AS) cardiovascular diseases. The previous studies have found that QXG inhibited isoproterenol (ISO)-induced myocardial remodeling. And its active ingredient, Icraiin, can inhibit ferroptosis by promoting oxidized low-density lipoprotein (xo-LDL)-induced vascular endothelial cell injury and autophagy in atherosclerotic mice. Another active ingredient, Salvianolic Acid B, can suppress ferroptosis and apoptosis during myocardial ischemia/reperfusion injury by reducing ubiquitin-proteasome degradation of Glutathione Peroxidase 4 (GPX4) and down-regulating the reactive oxygen species (ROS)- c-Jun N-terminal kinases (JNK)/mitogen-activated protein kinase (MAPK) pathway. AIM OF THE STUDY: The objective of this research was to assess the possible impact of QXG on atherosclerosis in postmenopausal individuals and investigate its underlying mechanisms. MATERIALS AND METHODS: Female ApoE-/- mice underwent ovariectomy and were subjected to a high-fat diet (HFD) to establish a postmenopausal atherosclerosis model. The therapeutic effects of QXG were observed in vivo and in vitro through intraperitoneal injection of erastin, G-protein Coupled Estrogen Receptor (GPER) inhibitor (G15), and silent Mucolipin Transient Receptor Potential Channel 1 (TRPML1) adenovirus injection via tail vein. UPLC-MS and molecular docking techniques identified and evaluated major QXG components, contributing to the investigation of QXG's anti-postmenopausal atherosclerotic effects. RESULTS: QXG increased serum Estradiol levels, decreased follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, which indicated QXG had estrogen-like effects in Ovx/ApoE-/- mice. Furthermore, QXG demonstrated the potential to impede the progression of AS in Ovx/ApoE-/- mice, as evidenced by reductions in serum triglycerides (TG), total cholesterol (TC), and low-density lipoprotein-cholesterol (LDL-C) levels. Additionally, QXG inhibited ferroptosis in Ovx/ApoE-/- mice. Notably, UPLC-MS analysis identified a total of 106 active components in QXG. The results of molecular docking analysis demonstrated that Epmedin B, Astragaloside II, and Orientin exhibit strong binding affinity towards TRPML1. QXG alleviates the progression of atherosclerosis by activating TRPML1 through the GPER pathway or directly activating TRPML1, thereby inhibiting GPX4 and ferritin heavy chain (FTH1)-mediated iron pendant disease. In vitro, QXG-treated serum suppressed proliferation, migration, and ox-LDL-induced MMP and ROS elevation in HAECs. CONCLUSION: QXG inhibited GPX4 and FTH1-mediated ferroptosis in vascular endothelial cells through up-regulating GPER/TRPML1 signaling, providing a potential therapeutic option for postmenopausal females seeking a safe and effective medication to prevent atherosclerosis. The study highlights QXG's estrogenic properties and its promising role in combating postmenopausal atherosclerosis.

Ferroptosis in ulcerative colitis: Potential mechanisms and promising therapeutic targets.

Ulcerative colitis (UC) is a complex immune-mediated chronic inflammatory bowel disease. It is mainly characterized by diffuse inflammation of the colonic and rectal mucosa with barrier function impairment. Identifying new biomarkers for the development of more effective UC therapies remains a pressing task for current research. Ferroptosis is a newly identified form of regulated cell death characterized by iron-dependent lipid peroxidation. As research deepens, ferroptosis has been demonstrated to be involved in the pathological processes of numerous diseases. A growing body of evidence suggests that the pathogenesis of UC is associated with ferroptosis, and the regulation of ferroptosis provides new opportunities for UC treatment. However, the specific mechanisms by which ferroptosis participates in the development of UC remain to be more fully and thoroughly investigated. Therefore, in this review, we focus on the research advances in the mechanism of ferroptosis in recent years and describe the potential role of ferroptosis in the pathogenesis of UC. In addition, we explore the underlying role of the crosslinked pathway between ferroptosis and other mechanisms such as macrophages, neutrophils, autophagy, endoplasmic reticulum stress, and gut microbiota in UC. Finally, we also summarize the potential compounds that may act as ferroptosis inhibitors in UC in the future.

Epidemiological study of pediatric rheumatic heart disease: An analysis from the Global Burden of Disease Study 2019.

BACKGROUND: Rheumatic heart disease (RHD) is the most common acquired heart disease among children in developing countries. However, there is a lack of systematic studies on the epidemiology of pediatric RHD. This study aimed to report the burden of pediatric RHD at global, regional, and national levels between 1990 and 2019, which may provide some reference for policymakers. METHODS: The numbers and age-standardized rates (ASRs) of incidence, prevalence, mortality, and disability-adjusted life years (DALYs) for childhood RHD from 1990 to 2019 were analyzed based on data obtained from the Global Burden of Disease Study 2019 (GBD 2019). In addition, Joinpoint regression analysis was used to assess temporal trends in the burden of childhood RHD. RESULTS: Globally, the number of incidence and prevalence cases of RHD in children increased by 41.89% and 40.88%, respectively, from 1990 to 2019. Age-standardized incidence rate (ASIR) and age-standardized prevalence rate (ASPR) increased with an average annual percentage change (AAPC) of 0.75% and 0.66%, respectively. In contrast, the age-standardized DALY rate and age-standardized mortality rate (ASMR) decreased significantly since 1990 by an AAPC of -3.47% and - 2.65%, respectively. Girls had a significantly higher burden of RHD than boys during the study period. At the age level, the RHD burden was significantly highest in the age group of 10-14 years. Moreover, the ASRs of incidence, prevalence, mortality, and DALYs were negatively associated with sociodemographic index (SDI). Nationally, Fiji had the most significant increase in incidence and prevalence, and Philippines had the most remarkable rise in DALYs and mortality rates. CONCLUSION: From 1990 to 2019, although the incidence and prevalence of childhood RHD increased globally, DALYs and mortality rates markedly reduced. Countries with lower levels of sociodemographic development shoulder a higher burden of childhood RHD. Children aged 10-14 years are critical populations for whom targeted measures are needed to reduce the RHD burden, while attention to girls cannot be neglected.

The application and mechanism of Chinese medicine in the upstream treatment of atrial fibrillation.

Upstream treatment of atrial fibrillation (AF, for short) is a new approach to the prevention and treatment of AF with non-antiarrhythmic drugs, which is essentially primary and secondary prevention of AF. The former refers to the prevention of AF by controlling risk factors such as diabetes, hypertension, and heart failure before AF occurs, and the latter mainly refers to targeting ion channels, inflammation, oxidative stress, and other pathways to reduce or reverse atrial electrical and structural remodeling, reduction of AF load, and reduction of the chance of AF occurrence or progression. More and more studies have shown that many traditional Chinese medicines, active ingredients of Chinese medicines, and Chinese herbal formulas have definite effects on the upstream treatment of AF, but their mechanisms of action are different. Therefore, we summarized the relevant literature on the application and mechanisms of Chinese medicine on the upstream treatment of AF in recent years, hoping to be helpful for subsequent studies.

Visual analysis of colorectal cancer and gut microbiota: A bibliometric analysis from 2002 to 2022.

A growing number of studies have shown that gut microbiota (GM) plays an essential role in the occurrence and development of colorectal cancer (CRC). The current body of research exploring the relationship between CRC and GM is vast. Nevertheless, bibliometric studies in this area have not yet been reported. This study aimed to explore the hotspots and frontiers of research on GM and CRC in the past 20 years, which may provide a reference for researchers in this field. The Web of Science Core Collection database was searched for publications on CRC and GM from 2002 to 2022. The scientometric softwares CiteSpace and VOSviewer were used to visually analyze the countries, institutions, authors, journals, and keywords involved in the literature. Keywords co-occurrence, cluster, and burst analysis were utilized to further explore the current state and development trends of research on GM and CRC. A total of 2158 publications were included in this study, with a noticeably rising annual publication trend. The majority of these papers are from 80 nations, primarily China and the USA. J Yu was the most active author and WS Garrett has the highest citation. Among all institutions, Shanghai Jiao Tong University has the largest number of papers. Most of the publications were published in the International Journal of Molecular Sciences, with Science being the most frequently cited journal. The 4 main clusters mainly involved probiotics, inflammation, molecular mechanisms, and research methods. Current research hotspots included "Fusobacterium nucleatum," "Escherichia coli," etc. Newly emerging research has focused predominantly on immune response, gene expression, and recent strategies for the treatment of CRC with GM. The relationship between GM and CRC will continue to be a hot research area. Changes in the composition of GM in patients with CRC, the potential molecular mechanisms as well as probiotics and natural products used in the treatment of CRC have been the focus of current research and hotspots for future studies.

Evolving trends and burden of iron deficiency among children, 1990-2019: a systematic analysis for the global burden of disease study 2019.

Objectives: We aimed to provide a timely, comprehensive, and reliable assessment of the burden of iron deficiency (ID) in children between 1990 and 2019 at the global, regional, and national levels to inform policymakers in developing locally appropriate health policies. Methods: Data related to ID among children younger than 15 years old were analyzed by sex, age, year, socio-demographic index (SDI), and location according to the Global Burden of Disease Study 2019 (GBD 2019). Age-standardized rates were used to compare the burden between different regions and countries. Furthermore, the Joinpoint regression model was used to assess temporal trends from 1990 to 2019. Results: In 2019, the number of prevalent cases and disability-adjusted life years (DALYs) for ID in children were 391,491,699 and 13,620,231, respectively. The global age-standardized prevalence and DALY rates for childhood ID in 2019 were 20,146.35 (95% confidence interval: 19,407.85 to 20,888.54) and 698.90 (466.54 to 1015.31) per 100,000, respectively. Over the past 30 years, the global prevalence of ID among children has been highest in low-SDI regions, particularly in Western Sub-Saharan Africa, South Asia, and Eastern Sub-Saharan Africa. Since 1990, the prevalence and DALY of ID in children have been declining in most geographic regions. Nationally, Ecuador, China, and Chile have shown the most significant decreases in prevalence. The greatest decline in age-standardized DALY rate was observed in Ecuador, while Burkina Faso experienced the highest increase. Bhutan had the highest prevalence and DALY rates in 2019. On the age level, the prevalence was relatively higher among the <5 years age group. At the gender dimension, the prevalence of ID in children overall was more pronounced in girls than in boys, as was the case for DALY. Conclusion: Although the burden of ID in children has been declining, this disease remains a major public health problem, especially in countries with low SDI. Children younger than 5 years of age are an important group for whom targeted measures are needed to reduce the burden of ID.

Long-term trends in the burden of colorectal cancer in Europe over three decades: a joinpoint regression and age-period-cohort analysis.

Background: The burden of colorectal cancer (CRC) in Europe is at a high level, but the epidemiological features have not yet been systematically studied. This study aimed to provide a timely and reliable assessment of the burden and trends of CRC in Europe to provide a scientific basis for its prevention and treatment. Methods: We analyzed data on CRC in 44 European countries between 1990 and 2019 from the Global Burden of Disease study (GBD) 2019. In addition, the joinpoint regression model was applied to reflect temporal trends. The age-period-cohort model was constructed to explore age, period, and birth cohort effects that influence the risk of morbidity and mortality. Results: In Europe, new cases, disability-adjusted life years (DALYs) and deaths of CRC rose by 70.01%, 22.88% and 38.04% from 1990 to 2019, respectively. The age-standardized incidence rate (ASIR) has increased, while age-standardized DALY rate and age-standardized mortality rate (ASMR) have declined. We found that men experienced a significantly higher CRC burden than women. Age-period-cohort analysis showed that the risk of incidence and mortality increased with age and time; and it was lower in the later-born cohort than the earlier-born cohort. Conclusion: ASIR for CRC in Europe generally trended upwards from 1990 to 2019, stabilizing in recent years but still at a high level. CRC burden varied considerably in different countries. There was a pronounced gender difference in CRC burden, and middle-aged and older men should be a priority population for CRC prevention and treatment.

Coronary heart disease and gut microbiota: A bibliometric and visual analysis from 2002 to 2022.

Background: Existing studies have indicated that gut microbiota is closely related to the occurrence and development of coronary heart disease(CHD). Gut microbiota and its metabolites may be important diagnostic markers for CHD in the future and are expected to become new targets for the prevention and treatment of CHD. However, the current studies exploring the link between CHD and gut microbiota are miscellaneous and poorly targeted, without bibliometric analysis available. Objective: The purpose of this research was to perform a bibliometric and visual analysis of published papers on the relationship between CHD and gut microbiota. The study also sought to identify principal authors, institutions, and countries to analyze the research status and trends of gut microbiota research in the field of CHD. Methods: The Web of Science Core Collection (WoSCC) database was searched for publications on CHD and gut microbiota between 2002 and 2022. CiteSpace 5.8. R1, VOSviewer 1.6.16, and Microsoft Excel 2019 software tools were utilized to perform this bibliometric analysis and visualization. Results: There were 457 qualified publications found in total, with the annual number of publications increasing. The United States dominated in this field. Hazen, Stanley l was the author of the most papers. Cleveland Clinic published the most papers of any institution. The six main clusters' specific characteristics were discovered through analysis of the co-occurrence of keywords: inflammation, diet, trimethylamine n-oxide, metabolism, cardiovascular disease, and myocardial infarction. Newly emerging research has focused predominantly on gut microbiota metabolites and recent strategies for intervention in coronary atherosclerosis. Conclusion: These results provided a useful perspective on current research and future prospects for the research on the link between CHD and gut microbiota, which may help researchers to select suitable collaborators and facilitate their research to elucidate the underlying molecular mechanisms of CHD, including the causes, prevention, and treatment.