Relationship between the natural cessation time of umbilical cord pulsation in full-term newborns delivered vaginally and maternal-neonatal outcomes: a prospective cohort study.

BACKGROUND: To analyze the impact of the time of natural cessation of the umbilical cord on maternal and infant outcomes in order to explore the time of clamping that would be beneficial to maternal and infant outcomes. METHODS: The study was a cohort study and pregnant women who met the inclusion and exclusion criteria at the Obstetrics and Gynecology Department of Qilu Hospital of Shandong University from September 2020 to September 2021. Analysis using Kruskal-Wallis rank sum test, Pearson's Chi-squared test, generalized linear mixed model (GLMM) and repeated measures ANOVA. If the difference between groups was statistically significant, the Bonferroni test was then performed. A two-sided test of P < 0.05 was considered statistically significant. RESULTS: A total of 345 pregnants were included in this study. The subjects were divided into the ≤60 seconds group (n = 134), the 61-89 seconds group (n = 106) and the ≥90 seconds group (n = 105) according to the time of natural arrest of the umbilical cord. There was no statistically significant difference in the amount of postpartum hemorrhage and the need for iron, medication, or supplements in the postpartum period between the different cord spontaneous arrest time groups for mothers (P > 0.05). The weight of the newborns in the three groups was (3316.27 ± 356.70) g, (3387.26 ± 379.20) g, and (3455.52 ± 363.78) g, respectively, and the number of days of cord detachment was 12.00 (8.00, 15.75) days, 10.00 (7.00, 15.00) days and 9.00 (7.00, 13.00) days, respectively, as the time of natural cessation of the cord increased. The neonatal lymphocyte ratio, erythrocyte pressure, and hemoglobin reached a maximum in the 61-89 s group at (7.41 ± 2.16) %, (61.77 ± 8.17) % and (194.52 ± 25.84) g/L, respectively. Lower incidence of neonatal hyperbilirubinemia in the 61-89 s group compared to the ≥90s group 0 vs 4.8 (P < 0.05). CONCLUSIONS: In full-term singleton vaginal births, maternal and infant outcomes are better when waiting for 61-89 s after birth for the cord to stop pulsating naturally, suggesting that we can wait up to 90s for the cord to stop pulsating naturally, and if the cord does not stop pulsating after 90s, artificial weaning may be more beneficial to maternal and infant outcomes.

Burden of drug use disorders in the United States from 1990 to 2021 and its projection until 2035: results from the GBD study.

BACKGROUND: Drug use disorders (DUDs) have emerged as one of the most significant public health crises, exerting a substantial influence on both community health and socio-economic progress. The United States (US) also suffers a heavy burden, it is necessary to figure out the situation from multiple perspectives and take effective measures to deal with it. Therefore, using the data from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2021, we evaluated this topic. METHODS: Annual data on DUDs-related burden were collected from the GBD study 2021. We calculated the indicator of estimated annual percentage change (EAPC) to evaluate the changing trend of burden. The Bayesian model for age-period-cohort was introduced to forecast the burden. RESULTS: In 2021, the number and age-standardized rate of prevalence were particularly prominent, with 12,146.95 thousand and 3821.43 per 100,000, respectively. Higher burden was also observed in males, 15-45 years old populations, and opioid use disorders subtype. From 1990 to 2021, the DUDs-related burden increased in the US and all states, especially in West Virginia; and the national death-related burden with the highest increase (EAPC = 7.96). Other significant inverse associations were seen between EAPC, age-standardized rates, and socio-demographic index (SDI). Moreover, in the next 14 years, the projected DUDs burden remains exigent. CONCLUSIONS: The burden of DUDs in the US is heavy and has been enlarging. This study proposes that greater attention should be paid to the strategies in males, the younger population, opioid use disorders, and low-SDI states implemented by decision-makers to achieve goals such as reducing burden.

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

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

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

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

Global burden of lung cancer attributable to ambient fine particulate matter pollution in 204 countries and territories, 1990-2019.

INTRODUCTION: Understanding the latest global spatio-temporal pattern of lung cancer burden attributable to ambient fine particulate matter pollution (PM2.5) is crucial to prioritize global lung cancer prevention, as well as environment improvement. METHODS: Data on lung cancer attributable to ambient PM2.5 were downloaded from the Global Burden of Disease Study (GBD) 2019. The numbers and age-standardized rates on lung cancer mortality (ASMR) and disability-adjusted life years (ASDR) were estimated by age, sex, region, and country. We used estimated annual percentage change (EAPC) to quantify the temporal trends of ASMR and ASDR from 1990 to 2019. RESULTS: In 2019, the number of global lung cancer deaths and DALYs attributable to ambient PM2.5 was approximately 0.31 million and 7.02 million respectively, among which more deaths and DALYs occurred in males. At GBD region level, the heaviest burden occurred in East Asia, accounting for over 50% worldwide, with China ranked first worldwide. The number of ambient PM2.5 attributable lung cancer deaths and DALYs has over doubled from 1990 to 2019, but high sociodemographic index (SDI) region had a rapid decrease, with EAPC -2.21 in ASMR (95% CI: -2.32, -2.09). The age-specific mortality rate or DALY rate has increased in all age groups in low to middle SDI regions from 1990 to 2019. The ASMR or ASDR showed an inverted V-shaped association with SDI. The EAPC in ASMR or ASDR was highly negatively correlated with ASMR or ASDR in 1990 and SDI in 2019, with coefficients around 0.70. CONCLUSIONS: The number of ambient PM2.5-related lung cancer deaths and DALYs has largely increased because of the increase of exposure to PM2.5, population growth, and aging. Local governments should do economic activities under the consideration of public health, especially in high-burden areas.

The global burden of disease attributable to ambient fine particulate matter in 204 countries and territories, 1990-2019: A systematic analysis of the Global Burden of Disease Study 2019.

Understanding the spatio-temporal patterns of the disease burden attributable to ambient PM2.5 across the world is essential for the prevention of related diseases, as well as ambient PM2.5 control. Following the framework and methodology of the Global Burden of Disease Study (GBD) in 2019, the global, regional, and national data on ambient PM2.5-attributable death and disability-adjusted life years (DALYs), and the age-standardized rates of mortality (ASMR) and disability-adjusted life years (ASDR) were summarized based on age, gender, year, location and specific diseases. We calculated the average annual percentage change (AAPC) to depict the secular trends of ASMR and ASDR from 1990 to 2019. In 2019, the global ambient PM2.5-related deaths and DALYs were 4,140,970 and 118.2 million, respectively, with 1,702,150 deaths and 47.5 million DALYs for females and 2,438,820 deaths and 70.7 million DALYs for male. In the 13 level-three causes, ischemic heart disease, stroke, chronic obstructive and pulmonary disease (COPD) were the leading three causes of deaths and DALYs attributable to ambient PM2.5. The number of global deaths and DALYs attributable to ambient PM2.5 has increased by 102.3% and 67.7% from 1990 to 2019, respectively. However, ASMR and ASDR showed little change. In the 13 level-three diseases, ischemic heart disease, stroke, COPD, diabetes mellitus, and lung cancer were the top five contributors to the increase of global deaths or DALYs, among which diabetes mellitus had the fastest increase of ASMR and ASDR, with AAPC of 1.5 (95% CI: 1.43, 1.58) and 2.21 (95% CI: 2.15, 2.27), respectively. The population attributable fractions (PAF) of causes in ASMR or ASDR varied significantly across regions, of which PAF of COPD, stroke and lung cancer were the top three. Regarding the GBD region, high PAF mainly occurred in North Africa and Middle East, South Asia, and East Asia. The age-specific PAFs of ischemic heart disease and stroke deaths and DALYs due to ambient PM2.5 were negatively correlated with age. ASMR and ASDR of overall PM2.5 related-burden showed an inverted "V/U" relationship with the socio-demographic index (SDI). The AAPC of ASMR and ASDR of the overall causes showed a strong negative correlation with SDI in 2019, especially at the SDI larger than 0.5. The deaths and DALYs attributable to ambient PM2.5 continued to increase under the context of population growth and aging. Decision-makers should consider controlling the PM2.5 emission when developing the economy.

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

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

Altered gut microbiome accompanying with placenta barrier dysfunction programs pregnant complications in mice caused by graphene oxide.

The wide use of graphene oxide (GO) has raised increasing concerns about the potential risks to environmental and human health. Recent studies have shown the vital role of gut microbiome in various pathological status or even exogenous exposure, but more detailed understanding about the effects of possible gut microbiome alterations under GO exposure on reproductive toxicology evaluations in pregnant mammals remained elusive. Here we found that orally administrated GO daily during gestational day (GD) 7-16 caused dose-dependent pregnant complications of mice on the endpoint (GD19), including decreased weight of dam and live fetus, high rate of resorbed embryos and dead fetus, and skeletal development retardation. Meanwhile in placenta tissues of pregnant mice exposed to GO at dose over 10 mg/kg, the expression levels of tight junctions (Claudin1 and Occludin) and vascular endothelial growth factor (VEGFA) decreased approximately by 30%-80%, meaning impaired placenta barrier. According to the data of fecal 16s RNA sequencing in 40 mg/kg dose group and the control group, gut microbiome showed dramatically decreased α- and ß-diversity, and upregulated Firmicutes/Bacteroidetes ratio owing to GO exposure. What's more, significantly differentiated abundance of Euryarchaeota is expected to be a special biomarker for failed pregnancy caused by GO. Notably, the result of Spearman correlation analysis suggested that there was a strong link (correlation coefficient>0.6) between perturbed gut microbiome with both abnormally expressed factors of placenta barrier and adverse pregnant outcomes. In summary, the damages of GO exposure to placenta barrier and pregnancy were dose-dependent. And GO exposure was responsible for gut microbiome dysbiosis in mice with pregnant complications. These findings could provide referable evidence to evaluate reproductive risk of GO to mammals.

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

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

Effect of O antigen ligase gene mutation on oxidative stress resistance and pathogenicity of NMEC strain RS218.

Escherichia coli is one of the primary causes of bacterial sepsis and meningitis in newborns. E. coli RS218, a prototype strain of neonatal meningitis E. coli (NMEC), is often used in research on the pathogenesis of NMEC. Phagocytes are crucial sentinels of immunity, and their antibacterial ability is largely determined by the capability to produce large amounts of ROS. The capacity of bacteria to endure oxidative pressure affects their colonization in the host. Here, we systematically screened the genes that plays key roles in the tolerance of the model of E. coli RS218 to peroxygen environment using a Tn5 mutant library. As a result, a gene encoding O antigen polymerase (O antigen ligase) that contains the Wzy_C superfamily domain (herein designated as Ocw) was identified in E. coli RS218. Furthermore, we constructed an isogenic deletion mutant of ocw gene and its complementary strain in E. coli. Our results revealed that ocw affects the lipopolysaccharide synthesis, ROS tolerance, and survival of E. coli in the host environment. The discovery of ocw provides important clues for better understanding the function of O-antigen.

Carbon Disulfide Induces Embryo Implantation Disorder by Disturbing the Polarization of Macrophages in Mice Uteri.

Carbon disulfide (CS2) induces embryo implantation disorders. Macrophages participate in the process of pregnancy. Therefore, we want to explore the effects of CS2 exposure on polarization and immune function of macrophages in pregnant mice uteri. The exposure times were gestation days 3 (GD3), 4 (GD4), and 5 (GD5), and the observation end points were arranged in a time series after CS2 exposure. The uterine tissues were collected to detect the expression levels of macrophages cytokines (IL-6, IL-12, TGF-ß1, and Vegf-a) and downstream regulatory cytokines of Th1-type (IL-2 and IFN-γ) and Th2-type (IL-10 and IL-4) by flow cytometry, ELISA, and q-PCR. The results showed that, compared with the controls, the ratios of M1/M2 macrophages in the endometrium significantly increased by 96%, 110%, and 177% at the GD4, GD6, and GD7 observation end points after GD3 exposure and increased about 3.88-fold and 2.37-fold at the GD6 and GD7 observation end points after GD4 exposure, respectively. In contrast, the ratio of M1 and M2 macrophages significantly reduced by 53% at the GD5 observation end point after GD3 exposure. Meanwhile, the expression levels of IL-6 were significantly increased about 2.00-fold for mRNA and 1.60-fold for protein at GD4 observation end points after GD3 exposure, and the mRNA levels of IL-12 increased about 3.61-fold at the GD6 observation end points after GD4 exposure. The mRNA levels of TGF-ß1 were significantly decreased by 41%, 25%, and 20% at the GD7 observation end points after exposure at GD3, GD4, and GD5, and the expression levels of Vegf-a mRNA and protein were decreased. Furthermore, the ratio of IL-2/IL4, IL-2/IL-10, IFN-γ/IL-4, and IFN-γ/IL-10 in the uterine tissue was significantly increased at the exposure groups. These findings suggest that the imbalanced polarization of macrophages is the key regulator in the progress of CS2-induced embryo loss.

The reproductive and developmental toxicity of nanoparticles: A bibliometric analysis.

Because of the advantages of nanoparticles (NPs) in a variety of industrial, biomedical, and consumer applications, they are intentionally (such as in medicine) or unintentionally (environment exposure) introduced into the human body. However, to date, the detrimental effects of NPs are still unclear, especially in reproductive and developmental toxicity. In this study, we researched 266 articles related to the reproductive and developmental toxicity of NPs from 2006 to December 2016 based on the database of the Web of Science. According to the bibliometric analysis, we found that China and the United States were the leading countries in this field and the major research trends might focus on the pathogenesis of NPs, such as oxidative stress, inflammation, and DNA damage. By this analysis, we provide new insights into the research trends and characteristics of the field.

Down-regulation of uterine LIF expression induced by the hormonal level disorder causes embryo implantation loss after mice exposed to carbon disulfide at peri-implantation.

Carbon disulfide (CS2) exposure can cause embryo implantation loss but the mechanism remains unclear. Earlier study revealed that the 4th day of gestation (GD4) and GD5 were the most sensitive exposure time on which the number of implanted embryos decreased obviously in mice. Leukemia inhibitory factor (LIF) in maternal uterine tissue is involved in embryo implantation, which is produced by endometrium and Th2 cells that participate in cellular adhesion of maternal-fetal interface. We herein investigated the effect of CS2 on the expression of LIF in uterine tissue and its regulatory mechanism in Kunming mice. Exposure was on GD3, GD4, GD5 and GD6, respectively, single administration (631.4 mg/kg), and the indexes were arranged in time series after exposure. The results showed that LIF gene breakage was captured at the 18th hour after exposure by Comet-FISH and the protein and mRNA of LIF in uterine tissue were down-regulated after exposure through the peri-implantation period. In addition, sex steroid hormones, progesterone (P4) and oestrogen (E2) were detected since they can stimulate synthesis of LIF from endometrial cells. Results showed that P4 and E2 in serum were down-regulated at all the endpoints of CS2 exposure groups. These findings suggested that the down-regulated LIF induced by the decreased P4 and E2 after mice exposure to CS2 might be important reasons for implantation disorders.

Inflammatory biomarkers mediate the association between polycyclic aromatic hydrocarbon exposure and dyslipidemia: a national population-based study.

Exploring the association between exposure to polycyclic aromatic hydrocarbons (PAHs) and the risk of dyslipidemia and possible mediating effects is essential for conducting epidemiological health studies on related lipid disorders. Therefore, our study aimed to elucidate the potential association between PAH exposure and dyslipidemia risk and further identify the mediating effects based on blood cell-based inflammatory biomarkers. This cross-sectional study was conducted on 8,380 individuals with complete survey data from the National Health and Nutrition Examination Survey (2001-2016). Multiple models (generalized linear regression model, restricted cubic spline model, Bayesian kernel machine regression, weighted quantiles sum regression) were used to assess the relationship between PAH co-exposure and the dyslipidemia risk and further identify potential mediating effects. Among the 8380 subjects, 2886 (34.44 %) had dyslipidemia. After adjusting for the confounding factors, the adjusted OR and 95% CI for dyslipidemia in the highest quartile of subjects were 1.30 (1.11, 1.51), 1. 22 (1.04, 1.43), 1.21 (1.03, 1.42), 1.29 (1.10, 1.52), 1.18 (1.01, 1.37), and 1.04 (0.89, 1.23) for 1-hydroxynaphthalene, 2-hydroxynaphthalene, 3-hydroxyfluorene, 2-hydroxyfluorene (2-FLU), 1-hydroxyphenanthrene, and 1-hydroxypyrene. The Bayesian kernel machine regression model also showed a positive correlation between PAH mixtures and dyslipidemia, and 2-FLU has the highest contribution. Mediation effect analyses showed that white blood cells and neutrophils were statistically significant in the association between PAHs and dyslipidemia. The present study suggests that individual and mixed PAH exposures may increase the risk of dyslipidemia in adults. Inflammatory biomarkers significantly mediated the relationship between PAH exposure and dyslipidemia. Environmental pollutants and their mechanisms should be more intensively monitored and studied.

Genetic and molecular characterization of metabolic pathway-based clusters in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive types of squamous cell carcinoma and represents a significant proportion of esophageal cancer. Metabolic reprogramming plays a key role in the occurrence and development of ESCC. Unsupervised clustering analysis was employed to stratify ESCC samples into three clusters: MPC1-lipid type, MPC2-amino acid type, and MPC3-energy type, based on the enrichment scores of metabolic pathways extracted from the Reactome database. The MPC3 cluster exhibited characteristics of energy metabolism, with heightened glycolysis, cofactors, and nucleotide metabolism, showing a trend toward increased aggressiveness and poorer survival rates. On the other hand, MPC1 and MPC2 primarily involved lipid and amino acid metabolism, respectively. In addition, liquid chromatography‒mass spectrometry-based metabolite profiles and potential therapeutic agents were explored and compared among ESCC cell lines with different MPCs. MPC3 amplified energy metabolism markers, especially carnitines. In contrast, MPC1 and MPC2 predominantly had elevated levels of lipids (primarily triacylglycerol) and amino acids, respectively. Furthermore, MPC3 demonstrated a suboptimal clinical response to PD-L1 immunotherapy but showed increased sensitivity to the doramapimod chemotherapy regimen, as evident from drug sensitivity evaluations. These insights pave the way for a more personalized therapeutic approach, potentially enhancing treatment precision for ESCC patients.

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

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

Causal atlas between inflammatory bowel disease and mental disorders: a bi-directional 2-sample Mendelian randomization study.

Background: The brain-gut axis link has attracted increasing attention, with observational studies suggesting that the relationship between common mental disorders and inflammatory bowel disease (IBD) may run in both directions. However, so far, it is not clear whether there is causality and in which direction. Methods: We conducted a bidirectional 2-sample Mendelian randomization study to investigate the relationship between IBD, including Crohn's disease (CD) and ulcerative colitis (UC), and mental disorders, using summary-level GWAS data. The main analysis was the inverse variance weighted method. IBD (including CD and UC), and nine mental disorders were used as both exposures and outcomes. Results: We found that UC could significantly lead to obsessive-compulsive disorder, attention deficit hyperactivity disorder, and autism spectrum disorder, with odds ratio (OR) of 1.245 (95% confidence intervals [CI]: 1.069-1.450; P=0.008), 1.050 (95%CI: 1.023-1.077; P=2.42×10-4), and 1.041 (95%CI: 1.015-1.068; P=0.002) respectively. In addition, we found that bipolar disorder and schizophrenia could increase the odds of IBD, with OR values of 1.138 (95%CI: 1.084-1.194; P=1.9×10-7), and 1.115 (95%CI: 1.071-1.161; P=1.12×10-7), respectively. Our results also indicate that obsessive-compulsive disorder could lead to IBD, especially for UC, with OR values of 1.091 (95%CI: 1.024-1.162; P=0.009), and 1.124 (95%CI: 1.041-1.214; P=0.004), respectively. Conclusions: Our findings indicate that the brain-gut axis involves the association between IBD, especially UC, and some mental disorders, which guides the targeted prevention, management, and mechanism exploration of these diseases.

Bibliometric analysis and visualization of research trends on HIV-1 capsid inhibitors (2000-2022).

Background: Acquired immunodeficiency syndrome (AIDS) has seriously endangered human life and health, the main pathogenic agent is human immunodeficiency virus type 1 (HIV-1). The combination antiretroviral therapy (cART) has shown serious drug resistance and side effects, and the discovery of HIV-1 capsid inhibitors is an effective way to solve the problem. Recent studies have shown significant progress in the research of HIV-1 capsid inhibitors. However, there is still a lack of comprehensive overview of bibliometric analysis in this field. This study aimed to provide the research trends and hotspots of HIV-1 capsid inhibitors. Method: Publications related to HIV-1 capsid inhibitors from 2000 to 2022 were searched on the Web of Science Core Collection (WoSCC) database and screened according to inclusion criteria. VOSviewer was conducted to evaluate the results. Results: 96 publications from 25 countries were finally included, and the number of annual publications related to HIV-1 capsid inhibitors showed an increasing trend. The United States was the most productive country with the most publication number, H-index, and total citation number, as well as the widest international cooperation. The most popular journal in this field was Journal of Virology. Drexel University was the most productive institution, and Simon Cocklin participated in the most publications. Keywords co-occurrence analysis exhibited that studying the molecular mechanism of capsid protein, discovering drug candidates, and improving antiretroviral therapy are the main and hot topics in this field. Conclusion: This is the first bibliometric study in the field of HIV-1 capsid inhibitors, which comprehensively analyzed the research trends and hotspots in this direction. This work is expected to provide the scientific community with new insights to promote the research of HIV-1 capsid inhibitors.

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

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

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

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