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Background: Increasing evidence has shown that environmental factors play a crucial role in the pathogenesis of periodontitis. Humans are simultaneously exposed to a variety of environmental brominated flame retardants (BFRs). However, the relationship between BFRs in periodontitis remains unclear. This study aimed to investigate the overall association between BFRs and periodontitis in a nationally representative US population and to further identify important chemicals., Methods: Data from 3322 NHANES participants from 2009 to 2016 were used. Serum BFRs were registered, including PBDE-28, PBDE-47, PBDE-85, PBDE-99, PBDE100, PBDE-153, PBDE-154, PBDE-183, PBDE-209 and PBB-153. Survey weighted generalized logistic regression models, restricted cubic splines (RCS) were conducted to assess single BFRs exposure with periodontitis. Meanwhile, weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were used to evaluate the overall association of BFRs mixtures with periodontitis and to identify significant chemicals., Results: A total of 3322 participants were included in the study, of whom 1795 had periodontitis. After adjusting for potential confounders, multiple logistic regression analysis revealed significant positive associations between serum levels of PBDE-28, PBDE-47, PBDE-85, PBDE-99, PBDE-100, PBDE-154, PBDE-183, and PBB-153 and the risk of periodontitis (all P < 0.05). A dose-response relationship was observed for many of these BFRs, with higher quantiles associated with an increased risk of periodontitis. WQS regression identified PBDE-183 (38.60%), PBDE-153 (21.20%), PBDE-209 (14.40%), and PBDE-99 (11.90%) as the BFRs with the largest weights contributing to the overall mixture effect on periodontitis risk. BKMR analysis further supported the positive association between serum BFRs and periodontitis, with most individual BFRs showing a positive trend, except for PBDE-153. Restricted cubic spline analysis revealed a generally increasing probability of periodontitis with increasing concentrations of BFRs, albeit with some nonlinear patterns for certain compounds., Conclusion: In conclusion, this study provides compelling evidence of a significant association between exposure to brominated flame retardants (BFRs) and an increased risk of periodontitis in a nationally representative sample of U.S. adults. Elevated serum levels of several BFRs, including PBDE-28, PBDE-47, PBDE-85, PBDE-99, PBDE-100, PBDE-154, PBDE-183, and PBB-153, were found to be positively associated with periodontitis, exhibiting a dose-response relationship., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background and Objective: Breast cancer is a leading cause of morbidity and mortality among women worldwide. This study aimed to assess the global burden of breast cancer and identify attributable risk factors across 204 countries and territories from 1990 to 2021., Methods: Using data from the Global Burden of Disease Study 2021, we analyzed the incidence, mortality, disability-adjusted life years (DALYs), and risk factors associated with breast cancer. We obtained and analyzed the age-standardized incidence rate (ASIR), age-standardized death rate (ASDR), and age-standardized DALYs rate from 1990 to 2021. We assessed geographical variations and the impact of the Socio-demographic Index (SDI) using regression analysis and stratification by SDI quintiles. Additionally, we estimated the risk factors attributable to breast cancer deaths and DALYs using the comparative risk assessment framework of the GBD study., Results: Globally, breast cancer incident cases increased from 875,657 in 1990 to 2,121,564 in 2021. The ASIR rose from 16.42 to 26.88 per 100,000 (95% CI: 1.54-1.60). High SDI regions showed the highest ASIR (66.89 per 100,000 in 2021), while Low SDI regions had the lowest (6.99 per 100,000 in 2021). The global ASDR decreased from 10.42 to 8.54 per 100,000, and the age-standardized DALYs rate decreased from 313.36 to 261.5 per 100,000 between 1990 and 2021. However, these improvements were not uniform across SDI regions. Risk factors included high body-mass index, alcohol use, tobacco, and high fasting plasma glucose, with variations across SDI regions., Conclusion: The global burden of breast cancer has increased significantly from 1990 to 2021, with disparities observed across SDI regions. While high SDI areas show improvements in mortality and DALYs, lower SDI regions face increasing burdens. Targeted interventions addressing modifiable risk factors and improving healthcare access in less developed regions are crucial for reducing the global impact of breast cancer., (© 2024. The Author(s).)

Background: Migraine, a widespread neurological condition, substantially affects the quality of life, particularly for adolescents and young adults. While its impact is significant, there remains a paucity of comprehensive global research on the burden of migraine in younger demographics. Our study sought to elucidate the global prevalence, incidence, and disability-adjusted life-years (DALYs) associated with migraine in the 15-39 age group from 1990 to 2021, utilizing data from the Global Burden of Disease (GBD) 2021 study., Methods: Our comprehensive study analyzed migraine data from the GBD 2021 report, examining the prevalence, incidence, and DALYs across 204 countries and territories over a 32-year span. We stratified the information by age, sex, year, geographical region, and Socio-demographic Index (SDI). To evaluate temporal trends in these metrics, we employed the estimated annual percentage change (EAPC) calculation., Results: Between 1990 and 2021, the worldwide prevalence of migraine among 15-39 year-olds increased substantially. By 2021, an estimated 593.8 million cases were reported, representing a 39.52% rise from 425.6 million cases in 1990. Global trends showed increases in age-standardized prevalence rate, incidence rate, and DALY rate for migraine during this period. The EAPC were positive for all three metrics: 0.09 for ASPR, 0.03 for ASIR, and 0.09 for DALY rate. Regions with medium SDI reported the highest absolute numbers of prevalent cases, incident cases, and DALYs in 2021. However, high SDI regions demonstrated the most elevated rates overall. Across the globe, migraine prevalence peaked in the 35-39 age group. Notably, female rates consistently exceeded male rates across all age categories., Conclusion: The global impact of migraine on youths and young adults has grown considerably from 1990 to 2021, revealing notable variations across SDI regions, countries, age groups, and sexes. This escalating burden necessitates targeted interventions and public health initiatives, especially in areas and populations disproportionately affected by migraine., (© 2024. The Author(s).)

Background: Depression is a significant mental health concern affecting the overall well-being of adolescents and young adults. Recently, the prevalence of depression has increased among young people. Nonetheless, there is little research delving into the longitudinal epidemiology of adolescent depression over time., Aims: To investigate the longitudinal epidemiology of depression among adolescents and young adults aged 10-24 years., Method: Our research focused on young people (aged 10-24 years) with depression, using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. We explored the age-standardised prevalence, incidence and disability-adjusted life-years (DALYs) of depression in different groups, including various regions, ages, genders and sociodemographic indices, from 1990 to 2019., Results: The prevalence, incidence and DALYs of depression in young people increased globally between 1990 and 2019. Regionally, higher-income regions like High-Income North America and Australasia recorded rising age-standardised prevalence and incidence rates, whereas low- or middle-income regions mostly saw reductions. Nationally, countries such as Greenland, the USA and Palestine reported the highest age-standardised prevalence and incidence rates in 2019, whereas Qatar witnessed the largest growth over time. The burden disproportionately affected females across age groups and world regions. The most prominent age effect on incidence and prevalence rates was in those aged 20-24 years. The depression burden showed an unfavourable trend in younger cohorts born after 1980, with females reporting a higher cohort risk than males., Conclusions: Between 1990 and 2019, the general pattern of depression among adolescents varied according to age, gender, time period and generational cohort, across regions and nations.

Background: Ischemic stroke remains a major contributor to global mortality and morbidity. This study aims to provide an updated assessment of rates in ischemic stroke prevalence, incidence, mortality, and disability-adjusted life-years (DALYs) from 1990 to 2021, specifically focusing on including prevalence investigation alongside other measures. The analysis is stratified by sex, age, and socio-demographic index (SDI) at global, regional, and national levels., Methods: Data for this study was obtained from the 2021 Global Burden of Diseases, Injuries, and Risk Factors Study (GBD). To quantify temporal patterns and assess trends in age-standardized rates of ischemic stroke prevalence (ASPR), incidence (ASIR), mortality (ASDR), and DALYs, estimated annual percentage changes (EAPCs) were computed over the study period. The analyses were disaggregated by gender, 20 age categories, 21 GBD regions, 204 nations/territories, and 5 SDI quintiles. R statistical package V 4.4.2 was performed for statistical analyses and plot illustrations., Findings: In 2021, the global burden of ischemic stroke remained substantial, with a total of 69,944,884.8 cases with an ASPR of 819.5 cases per 100,000 individuals (95% UI: 760.3-878.7). The ASIR was 92.4 per 100,000 people (95% UI: 79.8-105.8), while the ASDR was 44.2 per 100,000 persons (95% UI: 39.3-47.8). Additionally, the age-standardized DALY rate was 837.4 per 100,000 individuals (95% UI: 763.7-905). Regionally, areas with high-middle SDI exhibited the greatest ASPR, ASIR, ASDR, and age-standardized DALY rates, whereas high SDI regions had the lowest rates. Geospatially, Southern Sub-Saharan Africa had the highest ASPR, while Eastern Europe showed the highest ASIR. The greatest ASDR and age-standardized DALY rates were observed in Eastern Europe, Central Asia, as well as North Africa, and the Middle East. Among countries, Ghana had the highest ASPR, and North Macedonia had both the highest ASIR and ASDR. Furthermore, North Macedonia also exhibited the highest age-standardized DALY rate., Interpretation: Regions with high-middle and middle SDI continued to experience elevated ASPR, ASIR, ASDR and age-standardized DALY rates. The highest ischemic stroke burden was observed in Southern Sub-Saharan Africa, Central Asia, Eastern Europe, and the Middle East., Funding: None., Competing Interests: No competing interests declared., (© 2024 The Author(s).)

Background: Juvenile hemochromatosis (JH) is an early-onset, rare autosomal recessive disorder of iron overload observed worldwide that leads to damage in multiple organs. Pathogenic mutations in the hemojuvelin ( HJV ) gene are the major cause of JH., Case Summary: A 34-year-old male Chinese patient presented with liver fibrosis, diabetes, hypogonadotropic hypogonadism, hypophysis hypothyroidism, and skin hyperpigmentation. Biochemical test revealed a markedly elevated serum ferritin level of 4329 μg/L and a transferrin saturation rate of 95.4%. Targeted exome sequencing and Sanger sequencing revealed that the proband had a novel mutation c.863G>A (p.R288Q) in the HJV gene which was transmitted from his father, and two known mutations, c.18G>C (p.Q6H) and c.962&#95;963delGCinsAA (p.C321*) in cis, which were inherited from his mother. The p.R288W mutation was previously reported to be pathogenic for hemochromatosis, which strongly supported the pathogenicity of p.R288Q reported for the first time in this case. After 72 wk of intensive phlebotomy therapy, the patient achieved a reduction in serum ferritin to 160.5 μg/L. The patient's clinical symptoms demonstrated a notable improvement., Conclusion: This study highlights the importance of screening for hemochromatosis in patients with diabetes and hypogonadotropic hypogonadism. It also suggests that long-term active phlebotomy could efficiently improve the prognosis in severe JH., Competing Interests: Conflict-of-interest statement: The authors who have taken part in this study declare that they do not have anything to disclose regarding funding or conflicts of interest with respect to this manuscript., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: Patients with late life depression sometimes refuse to receive electroconvulsive therapy (ECT) owing to its adverse reactions. To alleviate patient's resistance, a novel ECT stimulation strategy named mixed-strategy ECT (msECT) was designed in which patients are administered conventional ECT during the first three sessions, followed by low energy stimulation during the subsequent sessions. However, whether low energy electrical stimulation in the subsequent stage of therapy affect its efficacy and reduce adverse reactions in patients with late life depression remains unknown. To explore differences between msECT and regular ECT(RECT) with respect to clinical efficacy and side effects., Methods: This randomized, controlled trial was conducted from 2019 to 2021 on 60 patients with late life depression who were randomly assigned to two groups: RECT or msECT. A generalized estimating equation (GEE) was used to compare the two stimulation strategies regarding their efficacy and side effects on cognition. Chi-squared test was used to compare side effects in the two strategies., Results: In the intent-to-treat group, the GEE model suggested no differences between-group difference in Hamilton Depression Rating Scale-17 score over time (Wald χ2=7.275, p=0.064), whereas the comparison of side effects in the two strategies favored msECT (Wald χ2=8.463, p=0.015) as fewer patients had adverse events during the second phase of treatment with msECT (χ2 =13.467, p=0.004)., Conclusion: msECT presents its similar efficacy to RECT. msECT may have milder side effects on cognition.

Ganoderic acids (GAs) are major functional components of Ganoderma lucidum . The study aimed to breed a new G. lucidum strain with increased contents of individual GAs. Two mating-compatible monokaryotic strains, G. 260125 and G. 260124, were successfully isolated from the dikaryotic G. lucidum CGMCC 5.0026 via protoplast formation and regeneration. The Vitreoscilla hemoglobin gene ( vgb ) and squalene synthase gene ( sqs ) were overexpressed in the monokaryotic G. 260124 and G. 260125 strain, respectively. Mating between the G. 260124 strain overexpressing vgb and the G. 260125 strain overexpressing sqs resulted in the formation of the new hybrid dikaryotic G. lucidum strain sqs-vgb. The maximum contents of ganoderic acid (GA)-T, GA-Me, and GA-P in the fruiting body of the mated sqs-vgb strain were 23.1, 15.3, and 39.8 μg/g dry weight (DW), respectively, 2.23-, 1.75-, and 2.69-fold greater than those in G. lucidum 5.0026. The squalene and lanosterol contents increased 2.35- and 1.75-fold, respectively, in the fruiting body of the mated sqs-vgb strain compared with those in the G. lucidum 5.0026. In addition, the maximum expression levels of the sqs and lanosterol synthase gene ( ls ) were increased 3.23- and 2.13-fold, respectively, in the mated sqs-vgb strain. In summary, we developed a new G. lucidum strain with higher contents of individual GAs in the fruiting body by integrating genetic engineering and mono-mono crossing., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhou, Kong, Huang, Li, Feng and Xu.)

Background: Accumulating evidence suggests a pivotal role of vitamin B2 in the pathogenesis and progression of prostate cancer (PCa). Vitamin B2 intake has been postulated to modulate the screening rate for PCa by altering the concentration of prostate-specific antigen(PSA). However, the relationship between vitamin B2 and PSA remains indeterminate. Hence, we conducted a comprehensive evaluation of the association between vitamin B2 intake and PSA levels, utilizing data from the National Health and Nutrition Examination Survey (NHANES) database., Methods: From a pool of 20,371 participants in the NHANES survey conducted between 2003 and 2010, a cohort of 2,323 participants was selected for the present study. The male participants were classified into four distinct groups based on their levels of vitamin B2 intake. We employed a multiple linear regression model and a non-parametric regression method to investigate the relationship between vitamin B2 and PSA levels., Results: The study cohort comprised of 2,323 participants with a mean age of 54.95 years (± 11.73). Our findings revealed a statistically significant inverse correlation between vitamin B2 intake (mg) and PSA levels, with a reduction of 0.13 ng/ml PSA concentration for every unit increase in vitamin B2 intake. Furthermore, we employed a fully adjusted model to construct a smooth curve to explore the possible linear relationship between vitamin B2 intake and PSA concentration., Conclusions: Our study in American men has unveiled a notable inverse association between vitamin B2 intake and PSA levels, potentially posing a challenge for the identification of asymptomatic prostate cancer. Specifically, our findings suggest that individuals with higher vitamin B2 intake may be at a greater risk of being diagnosed with advanced prostate cancer in the future, possibly indicating a detection bias. These results may offer a novel explanation for the observed positive correlation between vitamin B2 intake and prostate cancer., (© 2024. The Author(s).)

Objective: This modelling study aimed to estimate the burden for allergic diseases in children during a period of 30 years., Design: Population-based observational study., Main Outcomes and Measures: The data on the incidence, mortality and disability-adjusted life years (DALYs) for childhood allergic diseases, such as atopic dermatitis (AD) and asthma, were retrieved from the Global Burden of Disease study 2019 online database. This data set spans various groups, including different regions, ages, genders and Socio-Demographic Indices (SDI), covering the period from 1990 to 2019., Results: In 2019, there were approximately 81 million children with asthma and 5.6 million children with AD worldwide. The global incidence of asthma in children was 20 million. Age-standardised incidence rates showed a decrease of 4.17% for asthma, from 1075.14 (95% uncertainty intervals (UI), 724.63 to 1504.93) per 100 000 population in 1990 to 1030.33 (95% UI, 683.66 to 1449.53) in 2019. Similarly, the rates for AD decreased by 5.46%, from 594.05 (95% UI, 547.98 to 642.88) per 100 000 population in 1990 to 561.61 (95% UI, 519.03 to 608.29) in 2019. The incidence of both asthma and AD was highest in children under 5 years of age, gradually decreasing with age. Interestingly, an increase in SDI was associated with a rise in the incidence of both conditions. However, the mortality rate and DALYs for asthma showed a contrasting trend., Conclusions: Over the past three decades, there has been a worldwide increase in new asthma and AD cases, even though mortality rates have significantly declined. However, the prevalence of these allergic diseases among children varies considerably across regions, countries and age groups. This variation highlights the need for precise prevalence assessments. These assessments are vital in formulating effective strategies for prevention and treatment., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: This study aims to delineate the burden of congenital birth defects (CBDs) in children under 14 years of age from 1990 to 2019, using an age-period-cohort framework to analyse data from the Global Burden of Disease Study (GBD)., Methods: Data on prevalence cases, age-standardised prevalence rates (ASPRs), death cases, and age-standardised death rates (ASDRs) of congenital birth defects (CBDs) from 1990 to 2019 were obtained from GBD 2019. Using this data set, we conducted an age-period-cohort (APC) analysis to examine patterns and trends in mortality, prevalence, and disability-adjusted life years (DALYs) associated with CBDs, while exploring correlations with age, time periods, and generational birth cohorts. Furthermore, to quantify the temporal trends, we calculated the estimated annual percentage changes (EAPCs) for these parameters., Results: The global prevalence of CBDs decreased from 1404.22 to 1301.66 per 100 000 with an EAPC of -0.18% from 1990 to 2019. CBD mortality decreased by 42.52% between 1990 and 2019, with the global age-standardised death rate declining from 49.72 to 25.58 per 100 000. The age-standardised DALY rate decreased from 4529.16 to 2393.61 per 100 000. Prevalence declined most notably among older children. The risk of CBDs reached its lowest during adolescence (10-14 years) across all regions. The most recent period (2015-2019) showed a reduced risk of prevalence compared to 2000-2004. Earlier birth cohorts displayed declining tendencies followed by slight increases in risk., Conclusions: This study demonstrates encouraging global reductions in the burden of CBDs among children over the past three decades. Prevalence, mortality, and DALYs attributable to CBDs have exhibited downward trajectories, although regional disparities remain. APC analysis provides valuable insights to inform prevention and management strategies for pediatric CBDs., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests, (Copyright © 2024 by the Journal of Global Health. All rights reserved.)

Epilepsy is a profound disorder, accounting for roughly 1% of the global disease burden. It can result in premature death and significant disability. To comprehensively understand the current dynamics and trends of idiopathic epilepsy, a deep insight into its epidemiological attributes is vital. We evaluated the incidence, prevalence, mortality, and disability-adjusted life years associated with idiopathic epilepsy from 1990 to 2019 using data and methodologies from the Global Burden of Disease Study. In 2019, there were approximately 2,898,222 individuals diagnosed with idiopathic epilepsy. Intriguingly, from 1990 to 2019, the age-standardized incidence rate of idiopathic epilepsy was consistently lower in women compared to men. Over these three decades, global mortality connected to idiopathic epilepsy increased by 13.95%. However, within the same period, age-standardized death rates for idiopathic epilepsy decreased from 1.94 per 100,000 population to 1.46 per 100,000 population. Predictions indicate an increase in the incidence of idiopathic epilepsy across all age brackets through 2035, especially among the elderly aged 80 and above. Mortality rates are projected to climb for those aged 80 and above while remaining relatively unchanged in other age demographics. Idiopathic epilepsy continues to be a significant contributor to both disability and death. The findings of our study underscore the critical importance of incorporating idiopathic epilepsy management into modern healthcare frameworks. Such strategic inclusion can enhance public awareness of relevant risk factors and the range of available therapeutic interventions., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Infection is a major cause of death in children, and it is particularly important to identify biological indicators of early infection. Previous studies showed that the neutrophil CD64 (nCD64) index may be a useful biomarker for infection. The purpose of this study was to investigate use of the nCD64 index to identify infection in children from a pediatric ICU (PICU) in China., Methods: This prospective observational study enrolled 201 children who were admitted to our PICU and were divided into an infection group and a non-infection group. In each patient, C-reactive protein (CRP), nCD64 index, procalcitonin (PCT), and white blood cell count were measured during the first 24 h after admission. Receiver operating characteristic (ROC) analyses were used to determine the sensitivity, specificity, and diagnostic value of the nCD64 index for infection., Results: Among all 201 children, the infection group had greater levels of CRP, nCD64 index, and PCT (all p < 0.05). ROC analysis indicated the nCD64 index had a sensitivity of 68.8%, specificity of 90.7%, accuracy of 80.5%, and an optimal cut-off value of 0.14, which had better diagnostic value than CRP or PCT. For children with postoperative fever, the nCD64 index also distinguished systemic inflammatory response syndrome (SIRS) from infection with accuracy of 79%., Conclusions: The nCD64 index is a useful biomarker for the diagnosis of early infection in children admitted to the PICU., (© 2022. The Author(s).)

Background: Anoxia is characterized by changes in the morphology, metabolism, and function of tissues and organs due to insufficient oxygen supply or oxygen dysfunction. Gentiana straminea Maxim (G.s Maxim) is a traditional Tibetan medicine. Our previous work found that G.s Maxim mediates resistance to hypoxia, and we found that the ethyl acetate extract had the best effect. Nevertheless, the primary anti-hypoxia components and mechanisms of action remain unclear., Methods: Compounds from the ethyl acetate extraction of G.s Maxim were identified using UPLC-Triple TOF MS/MS. Then Traditional Chinese Medicine Systematic Pharmacology Database was used to filtrate them. Network pharmacology was used to forecast the mechanisms of these compounds. Male specific pathogen-free Sprague Dawley rats were randomly divided into six groups: (1) Control; (2) Model; (3) 228 mg/kg body weight Rhodiola capsules; (4) 6.66 g/kg body weight the G.s Maxim's ethyl acetate extraction; (5) 3.33 g/kg body weight the G.s Maxim's ethyl acetate extraction; (6) 1.67 g/kg body weight the G.s Maxim's ethyl acetate extraction. After administering intragastric ally for 15 consecutive days, an anoxia model was established using a hypobaric oxygen chamber (7000 m, 24 h). Then Histology, enzyme-linked immunosorbent assays, and western blots were performed to determine these compounds' anti-hypoxic effects and mechanisms. Finally, we performed a molecular docking test to test these compounds using Auto Dock., Results: Eight drug-like compounds in G.s Maxim were confirmed using UPLC-Triple TOF MS/MS and Lipinski's rule. The tumor necrosis factor (TNF) signaling pathway, the hypoxia-inducible factor 1 (HIF-1) signaling pathway, and the nuclear factor kappa-B (NF-κB) signaling pathway was signaling pathways that G.s Maxim mediated anti-anoxia effects. The critical targets were TNF, Jun proto-oncogene (JUN), tumor protein p53 (TP53), and threonine kinase 1 (AKT1). Animal experiments showed that the ethyl acetate extraction of G.s Maxim ameliorated the hypoxia-induced damage of hippocampal nerve cells in the CA1 region and reversed elevated serum expression of TNF-α, IL-6, and NF-κ B in hypoxic rats. The compound also reduced the expression of HIF-1α and p65 and increased the Bcl-2/Bax ratio in brain tissue. These findings suggest that G.s Maxim significantly protects against brain tissue damage in hypoxic rats by suppressing hypoxia-induced apoptosis and inflammation. Ccorosolic acid, oleanolic acid, and ursolic acid had a strong affinity with core targets., Conclusions: The ethyl acetate extraction of G.s Maxim mediates anti-hypoxic effects, possibly related to inhibiting apoptosis and inflammatory responses through the HIF-1/NF-κB pathway. The primary active components might be corosolic, oleanolic, and ursolic acids., (© 2022. The Author(s).)

Background: Metabolic reprogramming has emerged as a core hallmark of cancer, and cancer metabolism has long been equated with aerobic glycolysis. Moreover, hypoxia and the hypovascular tumor microenvironment (TME) are major hallmarks of pancreatic ductal adenocarcinoma (PDAC), in which glycolysis is imperative for tumor cell survival and proliferation. Here, we explored the impact of interleukin 1 receptor-associated kinase 2 (IRAK2) on the biological behavior of PDAC and investigated the underlying mechanism., Methods: The expression pattern and clinical relevance of IRAK2 was determined in GEO, TCGA and Ren Ji datasets. Loss-of-function and gain-of-function studies were employed to investigate the cellular functions of IRAK2 in vitro and in vivo. Gene set enrichment analysis, Seahorse metabolic analysis, immunohistochemistry and Western blot were applied to reveal the underlying molecular mechanisms., Results: We found that IRAK2 is highly expressed in PDAC patient samples and is related to a poor prognosis. IRAK2 knockdown led to a significant impairment of PDAC cell proliferation via an aberrant Warburg effect. Opposite results were obtained after exogenous IRAK2 overexpression. Mechanistically, we found that IRAK2 is critical for sustaining the activation of transcription factors such as those of the nuclear factor-κB (NF-κB) family, which have increasingly been recognized as crucial players in many steps of cancer initiation and progression. Treatment with maslinic acid (MA), a NF-κB inhibitor, markedly attenuated the aberrant oncological behavior of PDAC cells caused by IRAK2 overexpression., Conclusions: Our data reveal a role of IRAK2 in PDAC metabolic reprogramming. In addition, we obtained novel insights into how immune-related pathways affect PDAC progression and suggest that targeting IRAK2 may serve as a novel therapeutic approach for PDAC., (© 2022. Springer Nature Switzerland AG.)

Objectives: ECT is a rapid and effective treatment for depression. While efficacy is often remarkable over the initial 3-4 sessions, the efficacy of later sessions is less rapid, and the side-effects, especially cognitive impairment limit its use. To preliminarily compare the efficacy and acceptability of a novel hybrid-ECT (HECT) protocol for patients with major depressive disorder (MDD) with standard ECT, we conducted this pilot trial., Methods: Thirty patients were randomly assigned to ECT or HECT. Both arms received three ECT sessions (phase 1) but, in phase 2, the HECT arm received low-charge electrotherapy instead of ECT. The primary outcome was the change in 24-item Hamilton depression rating scale (HAMD-24) scores between baseline and the end of treatment. Cognitive function was assessed by repeatable battery for the assessment of neuropsychological status (RBANS), Stroop color word, and orientation recovery tests (ORT). Safety was measured by the drop-out rate and adverse events (AEs). Four visits were conducted at baseline, post-phase 1, post-phase 2, and at 1-month follow-up. Trial registration: Chinese Clinical Trial Registry (http://www.chictr.org.cn/), identifier: ChiCTR1900027701., Results: Patients in both arms showed significant within-group improvements in HAMD-24, but the between-group differences were non-significant. Participants in the HECT arm outperformed ECT patients for most cognitive tests at the end of treatment or at follow-up. There was a significantly lower AE rate and shorter ORT in phase 2 of the HECT ar., Conclusion: In this pilot trial, HECT was associated with fewer AEs and better cognitive function including executive and memory function, but its possible similar antidepressive efficacy needs to be further investigated in future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Xu, Zeng, Chen, Li, Jiang, Tan, Gu, Lai, Kong, Wang, Rong and Xie.)

The industrial control data set has many features and large redundancy, which has a certain impact on the training speed and classification results of the neural network anomaly detection algorithm. However, features are independent of each other, and dimension reduction often increases the false positive rate and false negative rate. The feature sequencing algorithm can reduce this effect. In order to select the appropriate feature sequencing algorithm for different data sets, this paper proposes an adaptive feature sequencing method based on data set evaluation index parameters. Firstly, the evaluation index system is constructed by the basic information of the data set, the mathematical characteristics of the data set, and the association degree of the data set. Then, the selection model is obtained by the decision tree training with the data label and the evaluation index, and the suitable feature sequencing algorithm is selected. Experiments were conducted on 11 data sets, including Batadal data set, CICIDS 2017, and Mississippi data set. The sequenced data sets are classified by ResNet. The accuracy of the sequenced data sets increases by 2.568% on average in 30 generations, and the average time reduction per epoch is 24.143%. Experiments show that this method can effectively select the feature sequencing algorithm with the best comprehensive performance., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Xue-Jun Liu et al.)