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.

OBJECTIVE: to explore the causal pathways underlying the short-term effects of deep dry needling (DDN) in people with chronic neck pain.
METHODS: explanatory longitudinal mediation analysis with repeatedly measured mediators and outcomes.
METHODS: primary care setting PARTICIPANTS: 128 patients with chronic neck pain.
METHODS: Participants were randomized in 2 groups; DDN of the neck muscles combined with stretching (N = 64) and stretching alone (N=64).
UNASSIGNED: Two outcomes (pain intensity and neck pain-related disability) and 3 candidate mediators (local pain pressure thresholds (PPTs), cervical range of motion (ROM) and neck muscle strength) were included. Pain intensity was also included as a competing mediator in the mediation analysis for disability. Mediators and outcomes were measured at three timepoints; post-intervention and 2- and 4-week follow-up. Age, gender and the baseline values of the outcome and mediators were included as pre-treatment mediator-outcome confounders.
RESULTS: reductions in pain intensity strongly mediated the short-term effects of DDN on disability, from post-intervention to 4-week follow-up. In addition, the attenuation of local hypersensitivity (via increasing PPTs) moderately mediated reductions in pain intensity at each timepoint. On the other hand, gains in cervical ROM contributed to reducing neck pain-related disability. Changes in muscle strength did not lead to better outcomes.
CONCLUSIONS: this novel study demonstrated that DDN effect on neck pain-related disability is strongly driven by the analgesic effects of this physical therapy modality. Increasing PPTs and cervical ROM seem to be also part of the mechanisms behind DDN\'s effect.

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: The causal association and biological mechanism linking serum 25-hydroxyvitamin D to stroke risk lacks epidemiological evidence.
OBJECTIVE: This study aimed to investigate the association between 25(OH)D concentration and stroke risk as well as the potential mediating factors.
METHODS: The community-based prospective community-based cohort study, the Chin-Shan Community Cardiovascular Cohort, was conducted from 1990 to December 2011, with external validation using a two-sample Mendelian randomization (MR) study.
METHODS: A total of 1,778 participants with serum 25-hydroxyvitamin D data were enrolled.
METHODS: In the CCCC observational study, the outcome was ascertained as stroke, while in the two-sample MR study, it was defined as ischemic stroke. Causal effects were estimated using restricted cubic spline analysis, COX proportional hazard ratios, mediation analysis, and two-sample MR.
RESULTS: Over 12 years (21,598 person-years) of follow-up, 163 participants (9.17%) developed stroke. Higher 25(OH)D concentrations were associated with lower stroke risk (hazard ratio: 0.64; 95% confidence interval, 0.43-0.96) after full-model adjustments. Mediation analysis showed a significant association between 25(OH)D concentration and stroke risk mediated by hypertension in unadjusted models (mediation percentage 23.3%, p=0.008) that became non-significant in full models (mediation percentage, 15.5%; p=0.072). Two-sample MR confirmed a significant inverse association between genetically determined 25(OH)D and stroke risk (IVW OR: 0.92; 95% CI: 0.85-0.99; p=0.036). However, hypertension had an insignificant mediating role in the Mendelian randomization study.
CONCLUSIONS: Higher 25(OH)D levels are linked to reduced stroke risk, potentially mediated by hypertension. Prioritizing blood pressure management may improve stroke prevention in 25(OH)D-deficient patients.

BACKGROUND: The \"Healthy Mother Healthy Baby\" (HMHB) study is a phase three, single-blind randomized clinical trial conducted at Holy Family Hospital (HFH) in association with Rawalpindi Medical University (RMU). We aimed to examine the mediators of a specialized psychosocial approach based on Cognitive Behavioural Therapy principles, targeting pregnant women experiencing anxiety. The HMHB intervention was effective in treating perinatal anxiety symptoms and preventing future depressive episodes.
METHODS: The trial randomized participants into two arms: the HMHB intervention or Enhanced Usual Care (EUC), following World Health Organization guidelines. The HMHB intervention comprised strategies to strengthen social support networks, improving mother-baby bonding and strategies to deal with interpersonal conflicts, economic challenges, and societal gender preferences using cognitive and behavioural techniques and culturally resonant illustrations. Participants underwent rigorous data collection at three pivotal timepoints: baseline, third trimester, and 6-weeks postnatal. The primary outcome was anxiety symptom severity scores using the Hospital Anxiety and Depression Scale (HADS) at 6-weeks post-childbirth. Four potential mediators - social support, behavioural activation, perceived stress, and pregnancy experience - were assessed in the third trimester of pregnancy.
RESULTS: A total of 1200 participants were randomized to the HMHB and EUC arms. In the six-week follow-up time point, 379 participants remained in the EUC group, and 387 continued in the HMHB group. Post-intervention, HMHB participants displayed significant improvements in postnatal anxiety and depression scores. Mediation analyses revealed social support and pregnancy hassles as significant mediators of the intervention\'s effect on postnatal anxiety outcomes, while only social support emerged as a significant mediator for depression outcomes.
CONCLUSIONS: The HMHB intervention showed promising results in improving anxiety and depression scores among pregnant women. Significant mediation effects suggest the importance of targeting social support and managing pregnancy-related hassles for optimal intervention effectiveness.

暂无摘要。

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.