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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.)

Quantum entanglement and correlations in the spin-1 Heisenberg chain with single-ion anisotropy are investigated using the quantum renormalization group method. Negativity and quantum discord (QD) are calculated with various anisotropy parameters △ and single-ion anisotropy parameters D . We focus on the relations between two abovementioned physical quantities and on transitions between the Néel, Haldane, and large- D phases. It is found that both negativity and QD exhibit step-like patterns in different phases as the size of the system increases. Interestingly, the single-ion anisotropy parameter D , which can be modulated using nuclear electric resonance (2020 Nature 579 205), plays an important role in tuning the quantum phase transition (QPT) of the system. Both the first partial derivative of the negativity and QD with respect to D or △ exhibit nonanalytic behavior at the phase transition points, which corresponds directly to the divergence of the correlation length. The quantum correlation critical exponents derived from negativity and QD are equal, and are the reciprocal of the correlation length exponent at each critical point. This work extends the application of quantum entanglement and correlations as tools for depicting QPTs in spin-1 systems., (© 2021 IOP Publishing Ltd.)

The study aimed to introduce a new analysis method of 24-hour intraocular pressure (IOP) and to propose the concept of overall IOP. Data of 24-hour IOP of a patient with a confirmed diagnosis of normal tension glaucoma was selected. Based on the present indexes including peak IOP, trough IOP, maximum difference, and mean IOP, new indexes were proposed, which included main IOP, duration of main IOP, and rate of IOP increase. A radar chart was drawn, and overall IOP was calculated. Overall IOP value = IOP distribution (sum of IOP value multiplied by the corresponding duration) × IOP fluctuation (standard deviation) × rate of IOP increase/100. By comparing two series of IOP data, the advantages of the new IOP indexes were demonstrated. The introduction of the concept of overall IOP expands the description of IOP from a single static state to a comprehensive dynamic state, which enables us to analyze the results of 24-hour IOP monitoring more thoroughly. (Chin J Ophthalmol, 2021, 57: 228-231) .

Introduction: Chlorpyrifos (CPF) is a organophosphate insecticide widely used in agriculture with attendant adverse health outcomes. Chronic exposure to CPF induces oxidative stress and elicits harmful effects, including hepatic dysfunction. Molecular hydrogen has been identified as a novel antioxidant which could selectively scavenge hydroxyl radicals., Objective: The aim of this study was to determine whether the intake of hydrogen-rich water (HRW) could protect rats from hepatotoxicity caused by sub-chronic exposure to CPF., Material and Methods: Rats were treated with hydrogen-rich water by oral intake for 8 weeks. Biochemical indicators of liver function, SOD and CAT activity, GSH and MDA levels were determined by the spectrophotometric method. Liver cell damage induced by CPF was evaluated by histopathological and electron microscopy analysis. PCR array analysis was performed to investigated the effects of molecular hydrogen on the regulation of oxidative stress related genes., Results: Both the hepatic function tests and histopathological analysis showed that the liver damage induced by CPF could be ameliorated by HRW intake. HRW intake also attenuated CPF induced oxidative stress, as evidenced by restored SOD activities and MDA levels. The results of PCR Array identified 12 oxidative stress-related genes differentially expressed after CPF exposure, 8 of chich, including the mitochondrial Sod2 gene, were significantly attenuated by HRW intake. The electron microscopy results indicated that the mitochondrial damage caused by CPF was alleviated after HRW treatment., Conclusions: The results obtained suggest that HRW intake can protect rats from CPF induced hepatotoxicity, and the oxidative stress signaling and the mitochondrial pathway may be involved in the protection of molecular hydrogen.

Background: This study aims to determine whether relative miR-122 levels in peripheral blood are correlated with chronic hepatitis B (CHB) and chronic hepatitis C (CHC) virus infection and viral replication to determine whether miR-122 can be a new marker for liver injury., Methods: MicroRNA (miRNA) was extracted from the peripheral blood of 20 CHB patients, 20 CHC patients, and 20 healthy controls. The levels of miR-122 were determined using fluorescence real-time reverse transcription PCR. Then, the associations of miR-122 with CHB and CHC were analyzed, and its correlation with other markers of liver function and viral replication were determined., Results: The expression level of miR-122 in patients with CHB was significantly higher when compared to subjects in the control group (P = 0.007) or CHC patients (P = 0.005). Furthermore, the miR-122 level in patients with CHC was somewhat higher when compared to healthy controls (66% higher), but the difference was not statistically significant (P = 0.229). MiR-122 levels were significantly correlated with ALT (correlation coefficient [R] = 0.7, P < 0.001), AST (R = 0.71, P < 0.001), and HBV NA (R = 0.9, P < 0.001). The regression analysis indicated that the AUC of miR-122 levels in the diagnosis of CHB was 0.87, with a sensitivity of 0.8 and a specificity of 0.8., Conclusion: MiR-122 can be used to distinguish healthy persons and patients with CHB infection with high sensitivity and specificity. These present findings presented that the complex and context-specific associations of miR-122 with liver diseases, suggesting that this may be a promising marker for liver injury., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The kinetics of elemental mercury (Hg 0 ) release from fly ashes and hydrated fly ash cement pastes was investigated using a homemade Hg measurement system. Three types of fly ash (FA) and ordinary Portland cement (OPC) were used to prepare cement pastes. After standard curing for 28 days, the hydrated cement paste (HCP) was ground into a fine powder for Hg emission measurements. Detectable Hg 0 was found released from both fly ashes and hydrated fly ash cement pastes. The results show that elevated temperatures and evaporation of the capillary pore water in wet HCP samples accelerate Hg 0 release. Both desorption of Hg 0 from the particle surface of HCP powder and migration of Hg 0 from the inner pores contribute to Hg 0 release. The kinetic calculation indicates that the hydration products of hydrated fly ash cement have little immobilization effect on Hg 0 , which is mainly physically encapsulated in the HCP particles by hydration products., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Phospholipids constitute the main component of biomembranes. During low-temperature storage and transportation of harvested bell peppers (Capsicum annuum), chilling injury participates in their decay. A primary cause of this chilling injury is phospholipid degradation. In this study, three genes encoding phospholipase D (PLD) were identified from bell peppers and their activities were examined under cold stress. Low temperature (4 °C) induced strong accumulation of the CaPLDα4 transcript, suggesting that it is associated with the phenomenon of phospholipid degradation and destruction of cell membranes. Low temperature also significantly induced increased amounts of NAM-ATAF1/2-CUC2 (NAC) domain transcription factors. CaNAC1 was found to interact with the promoter of CaPLD4 in a yeast one-hybrid screen. Electrophoretic mobility shift and ß-glucuronidase reporter assays demonstrated that CaNAC1 binds to the CTGCAG motif in the CaPLDα4 promoter, thereby activating its transcription and controlling phospholipid degradation. The ubiquitination sites of the CaNAC1 protein were characterized by liquid chromatography-tandem mass spectrometry. We conclude that CaNAC1 is a transcriptional activator of CaPLDα4 and suggested that it participates in the degradation of membrane lipids in bell peppers when they are stored at low temperature., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Postharvest broccoli is prone to yellowing during storage, which is the key factor leading to a reduction in value. To explore appropriate control methods, it is important to understand the mechanisms of yellowing. We analyzed the genes related to the metabolism of chlorophyll, carotenoids, and flavonoids and the transcription factors (TFs) involved in broccoli yellowing using transcriptome sequencing profiling. Broccoli stored at 10 °C showed slight yellowing on postharvest day 5 and serious symptoms on day 12. There were significant changes in chlorophyll fluorescence kinetics, mainly manifesting as a decrease in the Fv/Fm value and an increase in nonphotochemical quenching, during the yellowing process. Transcriptome sequencing profiles from samples of fresh broccoli and broccoli with slight and severe yellowing revealed 6, 5, and 4 differentially expressed genes involved in chlorophyll metabolism, carotenoid biosynthesis, and flavonoid biosynthesis, respectively. The transcription factor gene ontology categories showed that the MYB, bHLH, and bZip gene families were involved in chlorophyll metabolism. In addition, the transcription factor families included NACs and ethylene response factors (ERFs) that regulated carotenoid biosynthesis. Reverse transcription polymerase chain reaction further confirmed that bHLH66, PIF4, LOB13, NAC92, and APL were vital transcription factors that potentially regulated the CAO and HYD genes and were involved in chlorophyll metabolism and the carotenoid biosynthetic process. The flavonoid biosynthetic pathway was mainly regulated by MYBs, NACs, WRKYs, MADSs, and bZips. The results of the differentially expressed gene (DEG) and pigment content analyses indicated that the transcriptome data were accurately and positively associated with broccoli yellowing., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest.

To examine the feasibility of low-charge electrotherapy (LCE) in treating geriatric major depressive disorder (MDD) patients. Bi-temporal LCEs (approximately 25 mC) were performed with an electroconvulsive therapy (ECT) instrument three times per week. We used the Hamilton Depression Scale 17 (HAMD-17) and the Hamilton Anxiety Scale (HAMA) to assess the effects of LCE and the Mini-Mental State Examination (MMSE) to evaluate the cognitive function change before and after LCE. Six visits occurred at the baseline, after LCE sessions 3, 6, and 9, after the last session, and at the end of the one-month follow-up period. Four patients were enrolled in the study. Two patients completed all LCE sessions. Two patients withdrew during the trial, one due to the adverse event of uroschesis potentially caused by atropine and the other due to her own will. All four patients completed the follow-up sessions. The HAMD-17 and HAMA scores were reduced significantly at the last LCE session and the end of the follow-up period compared with the scores at the baseline. As measured by the MMSE, cognitive impairment showed no significant changes at the last LCE session and the end of the follow-up period compared with that at the baseline. In this case series, LCE showed potential as an alternative current-based treatment for treating geriatric MDD patients. Further research is needed to assess the efficiency and safety of LCE.

Bell peppers are valued for their plentiful vitamin C and nutritional content. Pepper fruits are susceptible to cold storage, which leads to chilling injury (CI); however, the crucial metabolic product and molecular basis response to cold stress have not been elucidated definitely yet. To comprehensively understand the gene regulation network and CI mechanisms in response to cold stress on a molecular level, we performed high-throughput RNA-Seq analysis to investigate genome-wide expression profiles in bell peppers at different storage temperatures (4 °C and 10 °C). A total of 61.55 Gb of clean data were produced; 3863 differentially expressed genes (DEGs) including 1669 up-regulated and 2194 down-regulated were annotated and classified between the CI group and control. Together, a total of 41 cold-induced transcription factor families comprising 250 transcription factors (TFs) were identified. Notably, numerous DEGs involved in biomembrane stability, dehydration and osmoregulation, and plant hormone signal transduction processes were discovered. The transcriptional level of 20 DEGs was verified by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Our results present transcriptome profiles of bell peppers in response to cold stress; the data obtained may be useful for the identification of key candidate genes and elucidation of the mechanisms underlying membrane damage during chilling injury., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Covalent organic frameworks (COFs), an emerging class of organic porous materials, have attracted intense attention due to their versatile applications. However, the deliberate fabrication of COF-based nanomaterials for nanomedical application remains challenging due to difficulty in their size- and structure-controlled synthesis and poor aqueous dispersibility. Herein, we report two boron-dipyrromethene (BODIPY)-decorated nanoscale COFs (NCOFs), which were prepared by the Schiff-base condensation of the free end -CHO (bonding defects in COFs) on the established imine-based NCOFs with the amino-substituted organic photosensitizer BODIPY via "bonding defects functionalization" approach. Thus BODIPY has been successfully nanocrystallized via the NCOF platform, and can be used for photodynamic therapy (PDT) to treat tumors. These NCOF-based PDT agents featured nanometer size (∼110 nm), low dark toxicity, and high phototoxicity as evidenced by in vitro and in vivo experiments. Moreover, the "bonding defects functionalization" approach might open up new avenues for the fabrication of additional COF-based platforms for biomedical treatment., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

A double-blind, randomised controlled pilot clinical trial was conducted to assess the potential effectiveness and safety of low-charge electrotherapy (LCE) for patients with schizophrenia. Bitemporal LCE (approximately 2.8 Joules) was administered three times a week. The Positive and Negative Syndrome Scale score was set as the outcome measure. Any adverse event (AE) was recorded. Three visits occurred at baseline, post-treatment, and after one month of follow-up. Twelve patients were randomised to the electroconvulsive therapy (ECT) group or LCE group (6 patients in each group). No patient withdrew during the study. The LCE group did not experience seizures during the trial. Patients in both groups showed significant improvements in clinical measures after treatment, and the reduction of all scale scores between the two groups was nonsignificant. The LCE group experienced significantly fewer AEs than the ECT group. Compared with ECT, LCE exerts similar antipsychotic effects while causing fewer AEs. Thus, LCE has the potential to be a safe and effective treatment for patients with schizophrenia, but further research is needed., (Copyright © 2018. Published by Elsevier B.V.)

The aim of the present study is to evaluate the vasodilation effects of Tongmai Yangxin Pills (TMYX) on rat mesenteric artery as well as its mechanism of action. The relaxation effects of TMYX extracts with different concentrations were determined on isolated rat mesenteric artery in normal condition as well as pretreating by phenylephrine and KCl. Vascular relaxation effects of TMTX were also determined in mesenteric artery preincubated with L-ANME and indomethacin or in endothelium denuded mesenteric artery. Moreover, effects of TMYX by 50 mg·L⁻¹ on NO secretion and the phosphorylation of eNOS in a cellular model of human umbilical vein endothelial cell (HUVEC) pretreated with or without L-NAME were also observed. The experimental results showed that TMYX has no obvious effect on vasodilation of arteries in normal or KCl pretreated condition, while it can dose-dependently relax the rat mesenteric artery with intact endothelium stimulated with phenylephrine at a maximal diastolic rate of (64.71±10.03)%. After preincubating with L-NAME for 15 min or removal of mesenteric artery endothelium, the maximal diastolic rate was decreased to (35.77±8.93)% and (25.85±10.84)% respectively. However, preincubating with indomethacin had no inhibitory effect on TMYX induced vascular relaxation. Meanwhile, TMYX at 50 mg·L⁻¹ could increase the expression of P-eNOS and the secretion of NO in HUVEC. L-NAME significantly inhibited NO release and phosphorylation of eNOS induced by TMYX. The results suggested TMYX exerted endothelium-dependent relaxation effects against PE-induced contractions of isolated rat mesenteric artery through NO-cGMP signaling pathway., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Objective: To investigate the characteristics of impairment of the visual field (VF) and retinal nerve fiber layer (RNFL) and the differences of progression pattern of early, middle and late stages of primary open-angle glaucoma (POAG) and normal-tension glaucoma (NTG) , and to analyze the correspondence of structure and function. Methods: Cross-sectional study. POAG patients, NTG patients and healthy volunteers who were enrolled from February 2008 to May 2017 at Department of Ophthalmology, Eye & ENT Hospital of Fudan University, underwent basic ophthalmic examination, Humphrey central 24-2 threshold test and optical coherence tomography. Patients were divided into early, middle and late stages according to the mean defect (MD) index of the VF test. According to the RNFL distributional characteristics, the pattern deviation map and RNFL were divided into 6 sectors. The differences of each sector's MD and RNFL thickness in the healthy group and groups of patients at 3 stages were analyzed using the Kruskal-Wallis test, and the correlation of MD and RNFL thickness of each sector was analyzed using the Pearson coefficient. Results: In the POAG group, there were 84 cases (84 eyes) including 35 eyes of early stage, 20 eyes of middle stage and 29 eyes of late stage, with a male/female ratio of 43∶41, aged (45±15) years. In the NTG group, 69 cases (69 eyes) included 30 eyes of early stage, 20 eyes of middle stage and 19 eyes of late stage, with a male/female ratio of 33∶36, aged (49±13) years. The control group had 23 cases (23 eyes), with a male/female ratio of 16∶17 and an age of (44±10) years. There was no significant difference in male/female ratio, age or best corrected visual acuity among the three groups. (1) In the middle stage of POAG, the VF defects of inferior hemi-fields were more severe than the superior ( t= 21.62, P= 0.000), which was opposite to the late stage of POAG ( t= -3.28, P= 0.003). In each stage of NTG, there was no significant difference between two hemi-fields. In the control group, the MD values(antilog) of VF in the superior peripheral arch (PEA), superior paracentral arch (PAA), inferior PEA and PAA, temporal and central regions were 0.87 (0.63-1.11)/L, 0.74 (0.61-0.83)/L, 0.72 (0.55-0.97)/L, 0.65 (0.51-0.87)/L, 0.69 (0.57-0.97)/L, and 0.82 (0.54-0.93)/L, respectively. The sectoral MD values in the VF sectors of POAG were significant compared with the control group ( P< 0.05): superior PAA for early stage [0.61 (0.18-0.92)/L, H= 21.58], superior PEA and PAA for middle stage [0.61 (0.15-0.87)/L, 0.21 (0.00-0.78)/L, H= 25.99, 34.91], superior PEA and PAA, inferior PEA and PAA for late stage [0.01 (0.00-1.13)/L, 0.00 (0.00-0.76)/L, 0.41 (0.00-1.07)/L, 0.21 (0.00-0.95)/L, H= 46.27, 54.19, 25.64, 28.10]. With the aggravation of POAG, superior PAA had the largest reduction percentage of sectoral MD. The sectoral MD values in the VF sectors of NTG were significant compared with the control group ( P< 0.05): superior PAA for early stage [0.54 (0.19-0.80)/L, H= 20.93], superior PAA for middle stage [0.60 (0.02-1.01)/L, H= 22.13], superior PEA and PAA, inferior PEA and PAA for late stage [0.33 (0.00-0.90)/L, 0.05 (0.00-0.92)/L, 0.16 (0.01-0.87)/L, 0.64 (0.02-1.10)/L, H= 37.66, 42.78, 35.15, 37.15]. With the aggravation of NTG, the largest reduction percentage of sectoral MD was found in superior PAA at the beginning but in inferior PAA at last. (2) The RNFL thickness of the control group in Region 1NI, 2TI, 3NS, 4TS, 5N, and 6T was 112.76 (63.54-150.99) μm, 134.89 (89.44-198.55) μm, 96.52 (57.32-158.79) μm, 120.96 (69.25-148.48) μm, 71.85 (65.03-95.47) μm, and 66.24 (55.44-90.97) μm, respectively. The sectoral thickness in the RNFL sectors of POAG were significant compared with the control group ( P< 0.05): 2TI for early stage [109.17 (43.77-173.86) μm, H= 31.50], 1NI, 2TI and 4TS for middle stage [71.54 (49.92-94.98) μm, 62.92 (42.33-102.73) μm, 84.20 (45.98-120.13) μm, H= 38.91, 49.89, 30.60], 1NI, 2TI, 3NS, 4TS, 5N and 6T for late stage [61.76 (39.32-97.99) μm, 59.59 (42.80-108.69) μm, 67.28 (42.56-117.96) μm, 65.16 (41.96-138.02) μm, 59.45 (21.04-78.48) μm, 53.74 (27.88-92.71) μm, H= 52.76, 55.06, 35.76, 41.72, 41.32, 29.93]. With the aggravation of POAG, at the beginning 2TI had the largest reduction percentage of RNFL thickness but 4TS had it at last. The sectoral thickness in the RNFL sectors of NTG were significantly different from the control group ( P< 0.05): 2TI for early stage [78.97 (47.77-131.45) μm, H= 28.86], 1NI, 2TI, 3NS and 4TS for middle stage [61.46 (49.69-97.38) μm, 74.51 (40.25-135.16) μm, 86.36 (42.70-105.06) μm, 83.60 (54.75-117.35) μm, H= 38.76, 35.64, 22.47, 24.14], 1NI, 2TI, 3NS, 4TS and 6T for late stage [61.45 (49.09-92.64) μm, 54.35 (37.40-102.62) μm, 63.72 (28.68-105.55) μm, 61.00 (44.92-108.49) μm, 50.33 (35.62-82.09) μm, H= 42.56, 51.50, 36.11, 47.44, 25.50]. With the aggravation of NTG, the sector with the largest reduction percentage of thickness changed from 2TI to NI and 4TS. (3) The VF superior PAA-RNFL 2TI had the highest Pearson correlation coefficient in POAG ( r= 0.630, P< 0.001), while it was the inferior PAA-4TS in NTG ( r= 0.645, P< 0.001). Conclusions: The impairment patterns of VF and RNFL in each stage of POAG and NTG are distinctly different from certain rules of aggravation. The sector with the strongest correlation of function-structure is the VF superior PAA-RNFL inferior temporal sector in POAG and inferior PAA-superior temporal sector in NTG. (Chin J Ophthalmol, 2018, 54: 811 - 819) .

Objective: To observe the effect of 2% ganciclovir eye drops on Posner-Schlossman syndrome (PSS) patients with positive cytomegalovirus (CMV) in aqueous humor. Methods: Prospective study. The cases clinically diagnosed as PSS with positive CMV were enrolled from August 2017 to January 2018 at Department of Ophthalmology, Eye & ENT Hospital of Fudan University. All patients underwent aqueous and serum analysis for CMV by the enzyme linked immunosorbent assay and polymerase chain reaction. The history and clinical signs were noted, 2% ganciclovir eye drops were prescribed for topical use (4 times per day), and the patients were followed up. The Pearson Chi-square test was used for the comparison of factors including keratic precipitates (KPs), and the Tyndall, and paired t test or Wilcoxon rank sum test was used for factors like intraocular pressure (IOP), corticoid dosage, and IOP lowering medication dosage. Results: Fifty cases (31 males and 19 females) clinically diagnosed as PSS with positive CMV had an average age of (38±13) years. Some characteristics could help to identify CMV-positive PSS: iris depigmentation (96%, 48/50), coin-shaped KPs, loss of corneal endothelium (an average loss rate of 10.8%±5.5%), and high IOP during attack[(47.8±9.9)mmHg,1 mmHg=0.133 kPa]. After topical antivirus therapy with the mean time of (5.4±2.7) weeks, the clinical manifestations of CMV positive PSS cases improved. The granulomatous or middle-sized KPs decreased from 94%(47/50) to 52%(26/50), the coin-shaped KPs almost disappeared [from 22%(11/50) to 2%(1/50)], and the Tyndall reaction disappeared [from 12%(6/50) to 0]. The mean IOP value decreased from (26.2±10.9) mmHg to (15.5±3.6) mmHg. Furthermore, corticoid use decreased (from 3 times per day to 0 time per day, by median value), the number of cases that did not use corticoids increased from 6% (3 cases) to 60% (30 cases), and 17 (65%) out of those 26 corticoid dependent patients could withdraw corticoids. The number of IOP lowering eye drops used also decreased (from 2 to 0, by median value), and the proportion of cases without IOP lowering medication increased from 24% (12 cases) to 58% (29 cases). There were statistical differences between post-treatment and pre-treameat (all P< 0.05).Thirteen cases that accepted CMV re-test of aqueous humor were all CMV DNA negative after treatment. Conclusion: Topical treatment with 2% ganciclovir eye drops has a good short-term effect on CMV-positive PSS patients by contributing to inflammation and IOP control. (Chin J Ophthalmol, 2018, 54: 833 - 838) .

Retinoic acid-inducible gene I-like receptor (RLR) is one of the most important pattern recognition receptors of the innate immune system that detects positive and/or negative stranded RNA viruses. Subsequently, it stimulates downstream transcription of interferon regulatory factor 3 (IRF3) and nuclear factor κB (NF-κB) inducing the production of interferons (IFNs) and inflammatory cytokines. Tumour necrosis factor receptor associated factor 6 (TRAF6) is a key protein involved in the RLR-mediated antiviral signalling pathway, recruiting additional proteins to form a multiprotein complex capable of activating the NF-κB inflammatory pathway. Despite TRAF6 playing an important role in regulating host immunity and viral infection, the deubiquitination of TRAF6 induced by viral infection remains elusive. In this study, we found that enterovirus 71 (EV71) infection attenuated the expression of Ubiquitin-specific protease 4 (USP4) in vitro and in vivo, while overexpression of USP4 significantly suppressed EV71 replication. Furthermore, it was found that EV71 infection reduced the RLR signalling pathway and enhanced the degradation of TRAF6. USP4 was also found to interact with TRAF6 and positively regulate the RLR-induced NF-κB signalling pathway, inhibiting the replication of EV71. Therefore, as a novel positive regulator of TRAF6, USP4 plays an essential role in EV71 infection by deubiquitinating K48-linked ubiquitin chains.

The purpose of the study was to investigate the effect of sophoridine on the proliferation and apoptosis of human gastric cancer MKN45 cells and the possible mechanism. MKN45 cells were randomly divided into control and sophoridine (including 6 subgroups) groups. Cell proliferation was detected by methyl thiazolyl tetrazolium (MTT) colorimetric method. The protein expression of high mobility group-box 3 (HMGB3) was observed by immunocytochemical staining and Western blot. Hoechst 33342 staining method was used to observe the morphological changes of cells treated with sophoridine. Apoptosis was detected by flow cytometry. The results showed that the proliferation of cells was inhibited by 48-hour treatment of sophoridine in a dose-dependent manner. Compared with control group, sophoridine group showed decreased HMGB3 protein expression and increased apoptotic rate. These results suggest that sophoridine can inhibit the proliferation of MKN45 cells and promote their apoptosis, which may be related to down-regulation of HMGB3 protein expression.

The function and clinical implication of ArfGAP with SH3 domain, ankyrin repeat, and PH domain 3 (ASAP3) in colorectal cancer (CRC) remains undefined. In the present study, we showed that the expression level of ASAP3 was dramatically increased in CRC and its upregulation was associated with American Joint Committee on Cancer stage (P < 0.001) and poor prognosis (P = 0.0022). The combination of stage and ASAP3 expression improved the prediction of survival in CRC patients. Suppression of ASAP3 inhibited cell proliferation by inducing G 1 phase arrest without influencing apoptosis. ASAP3 promoted growth of colon tumors in mice with colitis, and accelerated cell invasion and migration in vitro. Increased ASAP3 was associated with activation of the nuclear factor-κB (NF-κB) canonical pathway in CRC. Upregulation of ASAP3 increased the phosphorylation and nuclear translocation of the p65 NF-κB subunit. Mechanistically, ASAP3 interacts with NF-κB essential modulator (NEMO) and could reduce the polyubiquitinylation of NEMO. Overall, ASAP3 might regulate NF-κB via binding to NEMO. ASAP3 acts as an oncogene in colonic cancer and could be a potential biomarker of colon carcinogenesis., (© 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

In recent years, increscent emissions in the city of Beijing due to expanded population, accelerated industrialization and inter-regional pollutant transportation have led to hazardous atmospheric pollution issues. Although a number of anthropogenic control measures have been put into use, frequent/severe haze events have still challenged regional governments. In this study, a hybrid population-production-pollution nexus model (PPP) is proposed for air pollution management and air quality planning (AMP) with the aim to coordinate human activities and environmental protection. A fuzzy-stochastic mixed quadratic programming method (FSQ) is developed and introduced into a PPP for tackling atmospheric pollution issues with uncertainties. Based on the contribution of an index of population-production-pollution, a hybrid PPP-based AMP model that considers employment structure, industrial layout pattern, production mode, pollutant purification efficiency and a pollution mitigation scheme have been applied in Beijing. Results of the adjustment of employment structure, pollution mitigation scheme, and green gross domestic product under various environmental regulation scenarios are obtained and analyzed. This study can facilitate the identification of optimized policies for alleviating population-production-emission conflict in the study region, as well as ameliorating the hazardous air pollution crisis at an urban level., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Electroconvulsive therapy (ECT) is the most effective and rapid treatment for severe major depressive disorder (MDD) in elderly patients. The mechanism of ECT is unclear, and studies on ECT in elderly MDD patients by resting-state functional magnetic resonance imaging are rare. Thirteen elderly MDD patients were scanned before and after ECT using a 3.0T MRI scanner. Regional homogeneity (ReHo) and amplitude of low-frequency fluctuations (ALFF) were processed to compare resting-state function before and after treatment. Depression and anxiety symptoms of all patients abated after ECT. Decreased ReHo values in the bilateral superior frontal gyrus (SFG) were observed after ECT, and the values of right SFG significantly correlated with an altered Hamilton depression rating scale score. Increased ALFF values in the left middle frontal gyrus, right middle frontal gyrus, orbital part, and decreased ALFF values in the left midcingulate area, left precentral gyrus, right SFG/middle frontal gyrus after ECT were also observed. These results support the hypothesis that ECT may affect the regional resting state brain function in geriatric MDD patients., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Liver X receptors (LXRs) including LXRα and LXRβ are nuclear receptor transcription factors and play an important role in lipid and glucose metabolism. It has been previously reported that mice lacking LXRβ but not LXRα develop a severe urine concentrating defect, likely via a central mechanism. Here we provide evidence that LXRβ regulates water homeostasis through increasing aquaporin 2 (AQP2) protein levels in renal collecting ducts. LXRβ -/- mice exhibited a reduced response to desmopressin (dDAVP) stimulation, suggesting that the diabetes insipidus phenotype is of both central and nephrogenic origin. AQP2 protein abundance in the renal inner medulla was significantly reduced in LXRβ -/- mice but with little change in AQP2 mRNA levels. In vitro studies showed that AQP2 protein levels were elevated upon LXR agonist treatment in both primary cultured mouse inner medullary duct cells (mIMCD) and the mIMCD3 cell line with stably expressed AQP2. In addition, LXR agonists including TO901317 and GW3965 failed to induce AQP2 gene transcription but diminished its protein ubiquitination in primary cultured mIMCD cells, thereby inhibiting its degradation. Moreover, LXR activation-induced AQP2 protein expression was abolished by the protease inhibitor MG132 and the ubiquitination-deficient AQP2 (K270R). Taken together, the present study demonstrates that activation of LXRβ increases AQP2 protein levels in the renal collecting ducts via a posttranscriptional mechanism. As such, LXRβ represents a key regulator of body water homeostasis., (Copyright © 2017 the American Physiological Society.)

Objective: To investigate the alteration of retinal microcirculation and structural damage at macular region and evaluate their associations in primary open angle glaucoma (POAG) eyes. Methods: Cross-sectional study. Fifty-nine POAG patients (male/femal=35/24) were recruited from July 2015 to December 2015 in Eye, Ear, Nose and Throat Hospital of Fudan University. Twenty-eight eyes of early-stage POAG group (EG), 11 eyes of moderate-stage POAG group (MG) and 20 eyes of severe-stage POAG group (SG) were enrolled in this study. All patients underwent complete ophthalmological examinations and the general information was collected. The macular perfusion parameters (flow index & vessel area density) and the global/hemimacular retina thickness were derived from the 3D angio-retina and retina map procedures in the single optic coherence tomography (OCT) system with split-spectrum amplitude decorrelation angiography (SSADA) algorithm, respectively. One-way ANOVA analysis was conducted to compare the macular perfusion parameters, retinal thickness and visual field defects among three groups. Pearson partial regression analysis was used to calculate the correlations between different variables. Results: The mean flow index and vessel area density of MG eyes were 0.05±0.01 and 60.8%±7.9%, which were significantly lower than those indexes (0.06±0.01; 71.9%±4.6%) in EG eyes ( t= 5.11, P= 0.001; t= 5.05, P< 0.01). The full and inner retinal layer thicknesses of MG eyes were (270.3±24.6) μm and (98.4±13.3) μm, which were obviously thinner than those indexes (293.0±12.0 μm, 113.0±7.4 μm) in EG eyes ( t= 3.60, P< 0.01; t= 4.06, P< 0.01). However, there was no significant alteration of macular perfusion parameters and retinal thickness between MG and SG eyes. Furthermore, there was a significantly positive correlation between macular perfusion (flow index/vessel area density) and the macular retina thickness (full/inner thickness) ( R= 0.35-0.71, All P< 0.01). Conclusions: The microvascular perfusion and retinal thickness in MG eyes were lower than those in EG eyes. There was significant positive association between the retinal microvascular perfusion and structural damage. Furthermore, the association between microvascular perfusion and inner inferior retinal thickness is the strongest. (Chin J Ophthalmol, 2017, 53: 98-103) .

Esophageal cancer is one of the fastest rising types of cancers in China. The Kazak nationality is the highest-risk group in Xinjiang. In this work, an effective computer-aided diagnostic system is developed to assist physicians in interpreting digital X-ray image features and improving the quality of diagnosis. The modules of the proposed system include image preprocessing, feature extraction, feature selection, image classification, and performance evaluation. 300 original esophageal X-ray images were resized to a region of interest and then enhanced by the median filter and histogram equalization method. 37 features from textural, frequency, and complexity domains were extracted. Both sequential forward selection and principal component analysis methods were employed to select the discriminative features for classification. Then, support vector machine and K -nearest neighbors were applied to classify the esophageal cancer images with respect to their specific types. The classification performance was evaluated in terms of the area under the receiver operating characteristic curve, accuracy, precision, and recall, respectively. Experimental results show that the classification performance of the proposed system outperforms the conventional visual inspection approaches in terms of diagnostic quality and processing time. Therefore, the proposed computer-aided diagnostic system is promising for the diagnostics of esophageal cancer.

The geometrically frustrated spin-1 Blume-Capel model on an infinite sawtooth chain is exactly solved by the transfer matrix method. The magnetization, ground-state phase diagram, magnetocaloric properties, and specific heat of the system are investigated. The results indicate that: (i) Magnetization plateaus appear at zero temperature. Their number depends on the sign of the crystal field D. For D≥0 there are two magnetization plateaus; however, for D<0 five plateaus exist. At a finite temperature, thermal excitation will destroy these plateaus completely. (ii) Phase transition between any two long-range-ordered ground states, whose spin configurations are given in phase diagram, is the first-order one. The macroscopic degeneracy of the ground states described by the entropy only exists at phase coexistence points. (iii) As temperature approaches zero, magnetocaloric properties and entropy change sharply near phase coexistence points. (iv) The crossovers of the specific heat from a single-peak structure to double-peak ones can signal the phase coexistence points in ground-state phase diagram.

MicroRNAs are small noncoding RNA molecules that regulate gene expression at the post-transcriptional level. Compelling evidence reveals that there is a causative link between microRNAs deregulation and lung cancer development and metastasis. The aim of present study was to explore the function of miR-140-3p in the development and metastasis of lung cancer cell. Using real-time PCR, we detected the miR-140-3p expression of lung cancer tissues and its pared non-lung cancer tissue. Then, we evaluated the role of miR-140-3p in cell proliferation, invasion and migration using MTT, colony formation assay, Transwell invasion and Transwell migration assay in lung cancer cell lines. As a result, miR-140-3p expression level was lower in lung cancer tissues compared to adjacent normal lung cancer tissue. After miR-140-3p was upregulated in A549 or H1299 cells, cell proliferation, invasion and migration was notably attenuated. Furthermore, we identified ATP6AP2, which is associated with adenosine triphosphatases (ATPases), was a directly target of miR-140-3p in lung cancer cells. In conclusion, our data suggest miR-140-3p/ATP6AP2 axis might act as a potential therapeutic biomarker for lung cancer.

Objective: To assess the effectiveness of mindfulness-based stress reduction (MBSR) for chronic insomnia and combined depressive or anxiety symptoms of older adults aged 75 years and over., Design: A randomized, controlled, single-blind clinical trial., Patients and Methods: Participants included 60 adults aged 75 years and over with chronic insomnia. Participants were randomly assigned to the eight-week MBSR group or the wait-list control group. Assessments using the Pittsburgh Sleep Quality Index (PSQI), Self-rating Anxiety Sale (SAS), and Geriatric Depression Scale (GDS) were taken at baseline and post-treatment. For each outcome measure, a repeated measures analysis of variance was used to detect changes across assessments., Results: There was a significant time × group interaction for the PSQI global score (P = .006); the MBSR group had a decrease in the PSQI global score (Cohen׳s d = 1.12), while the control group did not (Cohen׳s d = -0.06). Among the PSQI components, there was a significant time × group interaction for daytime dysfunction (P = .048); Cohen׳s d of the MBSR group was 0.76, while Cohen׳s d of control group was -0.04. There was no significant time × group interaction for the SAS score (P = .116), while for the GDS there was a significant time × group interaction (P = .039); the Cohen׳s d value for the MBSR group was 1.20, and it was 0.12 for the control group., Conclusion: This study demonstrated that the MBSR program could be a beneficial treatment for chronic insomnia in adults aged 75 years and older., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Autophagy favors cell survival under hypoxia, and increasing evidence revealed that microRNAs regulate autophagy. We report here hypoxia increased the expression of miR-96 in prostate cancer cells, and miR-96 stimulated autophagy by suppressing MTOR. We found that inhibition of miR-96 abolished hypoxia-induced autophagy. Paradoxically, ectopic over-expression of miR-96 to a certain threshold, also abolished the hypoxia-induced autophagy. Further studies have shown that high levels of miR-96 inhibited autophagy through suppressing ATG7, a key autophagy-associated gene. Importantly, the miR-96 expression level threshold was determined, and the effects of miR-96 on autophagy on either side of the threshold were opposite. These data demonstrate hypoxia-induced autophagy is at least partially regulated by miR-96; miR-96 can promote or inhibit autophagy by principally inhibiting MTOR or ATG7 depending on the expression levels of miR-96. Our observation might reveal a novel regulatory mode of autophagy by microRNAs under hypoxia.

Objective: To investigate whether understanding of glaucoma is associated with psychological disturbance and vision-related quality of life (QoL) in patients with glaucoma., Design: A prospective, hospital-based, cross-sectional study., Setting: Shanghai, China., Participants: Five hundred patients with glaucoma were included in the study. Participants were asked to complete the glaucoma comprehension questionnaire, the Hospital Anxiety and Depression Scale (HADS) questionnaire, and the 25-item National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25)., Outcome Measures: Sociodemographic data and clinical data were collected. Multivariate adjusted linear regression analyses were performed to examine factors related to psychological disorder and QoL. The relationship between understanding of glaucoma and psychological status or QoL was analysed., Results: The mean age of patients was 56.5±17.2 years, and the mean duration of glaucoma was 4.6±6.3 years. About half (54.2%) of the patients had primary open angle glaucoma, 37.2% had primary angle closure glaucoma, and 8.6% had secondary glaucoma. The total score and the subscores of knowledge of glaucoma, compliance and habits were all negatively correlated with the HADS-Depression and HADS scores. For NEI VFQ-25, the total comprehension score was positively related to general vision, near activity, distance activity, social function, colour vision and the composite score. Habits had a significant influence on both HADS-Depression and the composite score of NEI VFQ-25., Conclusions: The level of understanding about glaucoma is an independent factor negatively associated with psychological disturbance and positively associated with QoL in patients with glaucoma. However, it is a subjective factor which can be regulated, so imparting knowledge about glaucoma and establishing appropriate habits might help patients alleviate psychological disturbance and enhance their QoL., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Patients with colorectal cancer (CRC) often develop liver metastases, in which case surgery is considered the only potentially curative treatment option. However, liver surgery is associated with a risk of ischemia-reperfusion (IR) injury, which is thought to promote the growth of colorectal liver metastases. The influence of IR-induced tumor necrosis factor alpha (TNF-α) elevation in the process still is unknown. To investigate the role of TNF-α in the growth of pre-existing micrometastases in the liver following IR, we used a mouse model of colorectal liver metastases. In this model, mice received IR treatment seven days after intrasplenic injections of colorectal CT26 cells. Prior to IR treatment, either TNF-α blocker Enbrel or low-dose TNF-α, which could inhibit IR-induced TNF-α elevation, was administered by intraperitoneal injection., Results: Hepatic IR treatment significantly promoted CT26 tumor growth in the liver, but either Enbrel or low-dose TNF-α pretreatment reversed this trend. Further studies showed that the CT26 + IR group prominently increased the levels of ALT and AST, liver necrosis, inflammatory infiltration and the expressions of hepatic IL-6, MMP9 and E-selectin compared to those of CT26 group. Inhibition of TNF-α elevation remarkably attenuated the increases of these liver inflammatory damage indicators and tumor-promoting factors., Conclusion: These findings suggested that inhibition of TNF-α elevation delayed the IR-enhanced outgrowth of colorectal liver metastases by reducing IR-induced inflammatory damage and the formation of tumor-promoting microenvironments. Both Enbrel and low-dose TNF-α represented the potential therapeutic approaches for the protection of colorectal liver metastatic patients against IR injury-induced growth of liver micrometastases foci.

Our previous studies have suggested that Staphylococcus aureus L-forms are able to pass through the placental barrier of mice from the maternal side to the fetal body and affect fetal growth and development, but little is known about the direct influence of S. aureus L-forms on embryos during the critical period of organogenesis. Mouse embryos at gestational day 8.5 were cultured in vitro for 48 h with 0, 50, 100, 200 or 400 c.f.u. S. aureus L-forms ml(-1). At the end of the culture period, the mouse embryos were assessed morphologically for viability, growth and development. Bacteriological and immunohistochemical staining were used to determine the existence of S. aureus L-forms in embryonic tissues. We found that both crown-rump length and head length of mouse embryos exposed to S. aureus L-forms at a concentration of 50 c.f.u. ml(-1) were reduced. When the mouse embryos were exposed to 100, 200 or 400 c.f.u. S. aureus L-forms ml(-1), the total morphological score, number of somites, dry embryo weight, yolk sac diameter, crown-rump length and head length were significantly lower than those of the control group. With the increased concentration of S. aureus L-forms in the culture medium, there were fewer normally developed embryos and more embryos with abnormalities or retardation in growth. S. aureus L-forms detected by Gram-staining and immunohistochemical detection of antigen were found in the tissues of embryos infected by S. aureus L-forms. These data suggest that S. aureus L-forms exert a direct teratogenic effect on cultured mouse embryos in vitro.