Exposure to environmental heavy metals may pose a risk factor for developing preeclampsia (PE) modified through intervention. This case-control study aimed to investigate the association between serum heavy metal concentrations and PE in pregnant women and whether hormones served as mediating factors in the impact of heavy metals on PE. From October 2020 to 2022, 160 patients with PE and 160 pregnant women with normal deliveries were recruited at Dongguan Songshan Lake Central Hospital. Serum concentrations of manganese (Mn), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), cadmium (Cd), lead (Pb), β-human chorionic gonadotropin (β-hCG), progesterone (P), estradiol (E2), testosterone (T), cortisol (Cort), and cortisone (Cor) were measured. Logistic, restricted cubic splines, weighted quantile sum and multivariate linear regression models were employed to account for different aspects and explore the relationships among heavy metals, hormones, and PE. Mediation model analysis was performed to assess the role of hormones in mediation. The median concentrations of Mn, E2, and Cort were lower in the PE group than in the control group. The median concentrations of Cu, Zn, β-hCG, and T were higher in the PE than in the control. Mn, E2, and Cort showed negative associations with PE, while Cu, Zn, β-hCG, and T demonstrated positive associations, as determined through logistic regression. Mn, Cu, and Zn displayed linear dose-response relationships with PE. Zn and Cu had high weights in the positive association model of mixed heavy metal exposure with PE. The mediation analysis revealed that serum E2, P, T, Cort, and Cort/Cor might be potential mediators of the association between heavy metals (Mn, Cu, and Zn) and PE.

BACKGROUND: Transgender women have a high prevalence of suicidal ideation, with stress and low interpersonal needs as its main risk factors. This study aimed to investigate the mediating role of interpersonal needs on the relationship between perceived stress and suicidal ideation among transgender women in China.
METHODS: A cross-sectional study was conducted in Shenyang and Kunming from April to September 2018. 247 transgender women were recruited. Sociodemographic statistics, perceived stress, interpersonal needs and suicidal ideation were obtained. Correlation analysis and mediation analysis were performed to test the relationship among perceived stress, suicidal ideation and interpersonal needs.
RESULTS: 14.6 % of the participants reported suicidal ideation within a year. Perceived stress was positively correlated with suicidal ideation (r = 0.228, p < 0.001), interpersonal needs and its three dimensions (r = 0.300-0.583, ps < 0.001)-thwarted belongingness, perceived burdensomeness and social exclusion. Interpersonal needs and its three dimensions were also positively correlated with suicidal ideation (r = 0.148-0.299, ps < 0.05). Interpersonal needs, perceived burdensomeness and social exclusion partly mediated the relationship between perceived stress and suicidal ideation, while thwarted belongingness didn\'t play a mediating role.
CONCLUSIONS: Cross-sectional study limited confirmation of causality between variables. The investigation didn\'t aim at the specific stressors of sexual minorities. And that participants came from only two regions might affect the generalization of the results.
CONCLUSIONS: We found a partial mediating role of interpersonal needs between stress and suicidal ideation. Stress reduction and increased social inclusion are needed to reduce suicidal ideation in transgender women.

BACKGROUND: In recent years, several studies have suggested that obesity may play an important role in cognitive impairment. Individuals with cognitive impairment often also exhibit depressive symptoms. This study aimed to explore the association between obesity and cognitive impairment and to elucidate the mediating role of depressive symptoms in this association.
METHODS: Older participants in the U.S. were examined in this cross-sectional study (n = 2391). The WWI was computed as follows: WWI = waist circumference/square root of body weight. The Consortium for Alzheimer\'s Disease Word Learning (CERAD-WL), the Animal Fluency Test (AFT), and the Digit Symbol Substitution Test (DSST) were used to evaluate cognitive function. Depression symptoms were evaluated with the Patient Health Questionnaire 9 (PHQ-9). Subgroup analysis and multiple logistic regression analysis were utilized to investigate the relationships between the WWI and depressive symptoms and cognitive decline. Threshold effects were computed using a two-segment linear regression model. To ascertain whether depression mediates the relationship between the WWI and cognitive impairment, mediation analysis was also employed.
RESULTS: A total of 2391 participants were included, 33.29 % of whom had cognitive impairment. There was a significant correlation between the WWI and depressive symptoms and cognitive function (P < 0.05). With increasing WWI quartiles, the prevalence of cognitive impairment increased (Q1: 27.09 %, Q2: 33.00 %, Q3: 31.44 %, Q4: 41.64 %). It was highly likely that the WWI and cognitive impairment were positively correlated (OR = 1.34, 95 % CI = 1.13, 1.59), and this link was steady across all subgroups (P for trend >0.05). A nonlinear curve with an inflection point of 10.71 connected the WWI and cognitive deterioration. A significant correlation was found between the WWI and cognitive impairment on the left side of the inflection point (OR = 3.58, 95 % CI = 1.57, 8.15). With a 5.4 % mediation rate, mediation analysis revealed that depressive symptoms mediated the relationship between cognitive impairment and the WWI.
CONCLUSIONS: There was a positive association between the WWI and the incidence of cognitive impairment in older Americans. Among other factors, depressive symptoms slightly mediated the association between the WWI and cognitive impairment. However, large-scale prospective studies are still needed to analyse the interactions between the three factors in depth.

BACKGROUND: Childhood trauma is closely tied to adult depression, but the neurobiological mechanisms remain unclear. Previous studies suggested associations between depression and large-scale brain networks such as the Ventral Attention Network (VAN) and Somatosensory Motor Network (SMN). This study hypothesized that functional connectivity (FC) within and between these networks mediates the link between childhood trauma and adult depression.
METHODS: The Childhood Trauma Questionnaire (CTQ) assessed developmental experiences, and the Hamilton Rating Scale for Depression (HAMD-17) gauged depressive symptoms. Resting-state functional magnetic resonance imaging (fMRI) analyzed FC within and between the VAN and SMN.
RESULTS: Depression group exhibited significantly higher HAMD and CTQ scores, as well as elevated FC within the VAN and between the VAN and SMN (P < 0.05). Positive correlations were found between HAMD total score and FC within the VAN (P < 0.05, r = 0.35) and between the VAN and SMN (P < 0.05, r = 0.34), as well as with CTQ total score (P < 0.05, r = 0.27). Positive correlations were also observed between CTQ total score and FC within the VAN (P < 0.05, r = 0.31) and between the VAN and SMN (P < 0.05, r = 0.29). In the mediation model, FC within and between the VAN and SMN significantly mediated childhood trauma and depression.
CONCLUSIONS: The cross-sectional design limits causal inference. The sample size for different trauma types is relatively small, urging caution in generalizing findings.
CONCLUSIONS: The study underscores the association between depression severity, VAN dysfunction, abnormal VAN-SMN FC, and childhood trauma. These findings contribute to understanding the neurobiological mechanisms underlying childhood trauma and depression.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) and metals were associated with decreased lung function, but co-exposure effects and underlying mechanism remained unknown.
METHODS: Among 1,123 adults from National Health and Nutrition Examination Survey 2011-2012, 10 urinary PAHs, 11 urinary metals, and peripheral white blood cell (WBC) count were determined, and 5 lung function indices were measured. Least absolute shrinkage and selection operator, Bayesian kernel machine regression, and quantile-based g-computation were used to estimate co-exposure effects on lung function. Mediation analysis was used to explore mediating role of WBC.
RESULTS: These models demonstrated that PAHs and metals were significantly associated with lung function impairment. Bayesian kernel machine regression models showed that comparing to all chemicals fixed at median level, forced expiratory volume in 1 s (FEV1)/forced vital capacity, peak expiratory flow, and forced expiratory flow between 25 and 75% decreased by 1.31% (95% CI: 0.72%, 1.91%), 231.62 (43.45, 419.78) mL/s, and 131.64 (37.54, 225.74) mL/s respectively, when all chemicals were at 75th percentile. In the quantile-based g-computation, each quartile increase in mixture was associated with 104.35 (95% CI: 40.67, 168.02) mL, 1.16% (2.11%, 22.40%), 294.90 (78.37, 511.43) mL/s, 168.44 (41.66, 295.22) mL/s decrease in the FEV1, FEV1/forced vital capacity, peak expiratory flow, and forced expiratory flow between 25% and 75%, respectively. 2-Hydroxyphenanthrene, 3-Hydroxyfluorene, and cadmium were leading contributors to the above associations. WBC mediated 8.22%-23.90% of association between PAHs and lung function.
CONCLUSIONS: Co-exposure of PAHs and metals impairs lung function, and WBC could partially mediate this relationship. Our findings elucidate co-exposure effects of environmental mixtures on respiratory health and underlying mechanisms, suggesting that focusing on highly prioritized toxicants would effectively attenuate adverse effects.

BACKGROUND: Remnant cholesterol (RC) reportedly contributes to the development of diabetes mellitus. However, evidence on the relationship between maternal RC and the risk of developing gestational diabetes mellitus (GDM) during pregnancy is limited. This study aimed to assess the relationship between maternal RC and GDM risk during early pregnancy, and explore the potential pathways involved in the relationship between RC levels and GDM risk.
METHODS: From 2018 to 2021, a prospective birth cohort study was designed and carried out in China. The associations of maternal RC and other lipid parameters with GDM risk were estimated using logistic regression models and restricted cubic splines. Subgroup analyses were performed stratified by prepregnancy body mass index (pre-BMI), maternal age and gravidity. Mediation analyses were conducted to explore the mediating effect of some related factors on the relationship between RC levels and the risk of GDM.
RESULTS: A total of 33,018 pregnant women were included. The median RC level was 0.47 ± 0.20 mmol/L. The prevalence of GDM was 15.19%. As RC quartiles increased, the incidence of GDM increased substantially, reaching 19.24% for the highest quartile of RC (P < 0.001). Maternal RC in the first trimester was positively correlated with GDM risk (OR: 2.254, 95% CI: 1.943-2.615). Compared to the lowest RC quartile, higher RC quartiles were correlated with an increased risk of GDM, and the ORs (95% CIs) for Q3 and Q4 were 1.208 (1.101-1.325) and 1.489 (1.364-1.626), respectively. Moreover, a linear dose-response relationship was found for this association (P for all < 0.001, P for nonlinearity > 0.05) and was consistent across subgroups with different pre-BMIs, maternal ages and gravidities (all P values for interactions > 0.05). Furthermore, the correlation between RC level and GDM risk was partially mediated by pre-BMI (9.20%) and blood glucose level (-11.1%).
CONCLUSIONS: Higher maternal RC levels in the early stage of pregnancy was positively associated with an increased risk of developing GDM. This association was partially mediated by pre- BMI and blood glucose levels.

BACKGROUND: Previous studies have shown that physical activity (PA) and leisure sedentary behaviors (LSB, including leisure television watching) are linked to gastroesophageal reflux disease (GERD). However, the associations between PA/LSB and GERD remain controversial. In this study, we aimed to reveal whether these associations reflect causal relationships and reveal the potential mechanisms of these relationships using bidirectional and two-step Mendelian randomization (MR) analyses.
METHODS: We obtained genome-wide association study (GWAS) summary statistics for PA/LSB, four common risk factors (including cigarettes smoked per day, alcoholic drinks per week, triglycerides, total cholesterol) and GERD from published GWASs. A bidirectional MR analysis was performed to identify causal relationships between PA/LSB and GERD. Then, a series of sensitivity analyses were performed to verify the robustness of the results. Finally, a mediation analysis via two-step MR was conducted to investigate any effects explained by common risk factors in these relationships.
RESULTS: Genetically predicted per 1-SD increase in leisure time television watching significantly increased the risk of GERD in the bidirectional MR analysis (OR = 1.33; 95% CI: 1.14-1.56; P = 2.71 × 10- 4). Sensitivity analyses successfully verified the robustness of the causal relationship. Further mediation analysis showed that this effect was partly mediated by increasing cigarettes smoked per day, with mediated proportions of 18.37% (95% CI: 11.94-39.79%).
CONCLUSIONS: Our findings revealed a causal relationship between leisure television watching and an increased risk of GERD, notably, the causal effect was partially mediated by cigarettes smoked per day. These findings may inform prevention and management strategies directed toward GERD.

OBJECTIVE: The objective of this study is to elucidate the causal association between asthma and alopecia areata (AA) through the application of Mendelian randomization (MR) analysis, leveraging summary data from genome-wide association studies (GWAS). Additionally, it explores potential mediating factors.
METHODS: Mendelian randomization (MR) analysis was employed to investigate the causal relationship between asthma and AA using genetic instrumental variables (IVs) for asthma, 91 circulating inflammatory proteins, and AA extracted from large-scale GWAS. The primary analytical approach utilized the inverse-variance weighted (IVW) method, supplemented by weighted median and MR-Egger methods to assess robustness. Tests for heterogeneity and pleiotropy were conducted to ensure result reliability. Furthermore, the study examined the mediating role of circulating inflammatory proteins in the asthma-AA relationship.
RESULTS: The findings revealed an increased risk of AA among asthma patients (odds ratio (OR) = 14.070; 95% confidence interval (CI) = 1.410-140.435; P = 0.024). Interleukin-33 (IL-33) emerged as a significant mediator in the asthma-AA relationship, explaining 13.1% of the mediation effect. Bidirectional Mendelian randomization analyses did not establish a causal effect of AA on asthma occurrence.
CONCLUSIONS: This study, utilizing Mendelian Randomization, elucidates the causal link between asthma and AA, highlighting the mediating role of IL-33. These findings underscore the importance of considering AA risk in asthma management and offer insights for potential therapeutic strategies targeting IL-33. Future research should explore additional biomarkers and mediating mechanisms between asthma and AA to enhance treatment approaches and patient quality of life.

UNASSIGNED: Body dissatisfaction significantly impacts depression among adolescents with polycystic ovary syndrome (PCOS). This relationship is compounded by various factors. Our study aims to explore the roles of self-esteem and self-compassion in the relationship between body dissatisfaction and depression in adolescent with PCOS.
UNASSIGNED: A cross-sectional study was conducted at the Shanghai First Maternity and Infant Hospital, involving 287 adolescents diagnosed with PCOS from January 2020 to December 2021. Participants completed validated questionnaires covering body dissatisfaction, self-esteem, self-compassion and depression. We utilized correlation and mediation analyses to examine the relationships and mediating effects among these variables.
UNASSIGNED: Body dissatisfaction had a significant positive effect on depression (β = 4.254, p < 0.001). Conversely, self-esteem (β = -0.944, p < 0.001) and self-compassion (β = -0.318, p < 0.001) were negative predictors of depression. Both self-esteem [β = 3.405, 95% CI = (0.151, 0.305)] and self-compassion [β = 1.525, 95% CI = (0.045, 0.165)] were shown to partially mediate the relationship between body dissatisfaction and depression, explaining 37.07% and 16.61% of the total effect, respectively.
UNASSIGNED: This study highlights the importance of fostering self-esteem and self-compassion among adolescents with PCOS to buffer the depressive effects of body dissatisfaction. Interventions aimed at promoting accurate and positive body perceptions, enhancing self-esteem, fostering a supportive attitude toward personal challenges, and maintaining positive emotional states are recommended to decrease the incidence of depression.

This study aimed to investigate the relationships among growth mindset, cognitive fusion, bias towards negative information, and bias towards positive information. The Growth Mindset Scale, the Attention to Positive and Negative Information Scale, and the Cognitive Fusion Questionnaire were employed. A total of 470 college students in China participated in the study. The findings showed a negative correlation between a growth mindset and cognitive fusion. In addition, a parallel mediation analysis demonstrated that bias towards negative information mediated the relationship between a growth mindset and cognitive fusion and that the indirect effect was significant. However, the mediation of bias towards positive information in this model was not significant. These results suggest that possessing a growth mindset is advantageous for mental health.