1.Association between placental cortisol and neurodevelopment in 3-month-old infants
Shuangjie YU ; Jinfang ZHANG ; Ye LI ; Jing FAN ; Can LIU ; Suzhen GUAN
Journal of Environmental and Occupational Medicine 2025;42(4):420-426
Background During pregnancy, negative emotions such as anxiety and depression may induce cortisol disruption. Cortisol can be transmitted to the fetus through the placental barrier, thereby affecting the neurodevelopment of the offspring. Objective To investigate the relationship between placental cortisol, maternal depression during pregnancy, and neurodevelopment of 3-month-old infants. Methods From September 2022 to September 2023, 171 pregnant women ordered routine prenatal checks at the obstetrics outpatient department of a tertiary hospital in Ningxia were selected using a prospective cohort design. After providing informed consent, these women participated in a questionnaire survey that covered general individual characteristics, prenatal depression, and sleep quality. At birth, placental samples were collected to measure cortisol levels using ELISA kits. Follow-up assessments on the neurodevelopmental of 3-month-old infants were conducted using the Warning Sign for Children Mental and Behavioral Development. LASSO regression analysis was conducted to screen the influencing factors of depression during pregnancy. Huber regression analysis was then applied to assess potential linear relationship between depression during pregnancy and placental cortisol levels. Log-binomial regression was used to analyze the linear relationships between cortisol levels and neurodevelopmental delay in 3-month-old infants. Additionally, a mediation effect model was fitted using R 4.3.3 to assess possible mediating role of cortisol in the association between prenatal depression and neurodevelopmental delay in 3-month-old infants. Results The positive rate of prenatal depression was 33.33%. Nine factors affecting prenatal depression were identified by LASSO regression, including rural residence, high school education or above, extroverted personality characteristics, moderate early pregnancy reactions, baby sex expectation, prenatal anxiety, family dysfunction, exposure to stressful life events during pregnancy, and moderate prenatal sleep quality. The Huber regression model showed a positive linear correlation between prenatal depression and placental cortisol (P<0.05). With or without controlling confounding factors, the results of log-binomial regression modeling showed that cortisol levels were associated with a reduced risk of neurodevelopmental delay in 3-month-old infants (crude model: RR=0.988, 95%CI:
2.Mediating role of sleep quality between job burnout and depressive symptoms among Ningxia occupational population
Mengjun CHANG ; Shuangjie YU ; Jin JI ; Jiashu ZHU ; Ye LI ; Suzhen GUAN
Journal of Environmental and Occupational Medicine 2025;42(5):557-564
Background Job burnout and depressive symptoms are prevalent among occupational populations, with a close relationship between them. Sleep quality, as a potential mediating factor, significantly affects the mental health of workers. Objective To explore the relationship between job burnout, sleep quality, and depressive symptoms, and determine whether sleep quality mediates the relationship between job burnout and depressive symptoms. Methods From April 25 to May 1, 2024, this study employed cluster sampling to conduct a questionnaire survey among individuals engaged in various occupations across five cities in the Ningxia Hui Autonomous Region. The questionnaires included socio-demographic information, as well as the Chinese Maslach Burnout Inventory (CMBI), the Pittsburgh Sleep Quality Index (PSQI), and the Patient Health Questionnaire-9 (PHQ-9) for assessing burnout, sleep quality, and depressive symptoms, respectively. Out of the
3.A case-control study on association between shift work and type 2 diabetes mellitus
Can LIU ; Jing FAN ; Weile WU ; Wenjiong LIANG ; Yulong LIAN ; Suzhen GUAN
Journal of Environmental and Occupational Medicine 2025;42(7):827-832
Background With economic development and globalization, shift work has become prevalent across industries. Its relationship with type 2 diabetes mellitus (T2DM) attracts increasing attention. Objective To thoroughly explore the relationship between shift work and T2DM, and analyze the impacts of specific shift patterns on T2DM, so as to provide a basis for formulating reasonable shift schedules. Methods We conducted a 1:2 matched case-control study among adults (20-60 years) who ordered occupational health examinations at the Wuxi No.8 People's Hospital from November to December 2023. The case group comprised 200 T2DM patients, while the controls were 400 age-stratified matched non-diabetic individuals. General demographic characteristics, behavioral habits, medical history, and shift work exposure data (including shift patterns, frequency, and length of service) 5 years prior to diagnosis were collected through standardized questionnaires. Logistic regression adjusted for selected confounders was employed to evaluate the association between shift work and T2DM. Results The logistic regression analysis demonstrated that shift work was associated with an increased risk of T2DM. After adjusting for confounding factors, shift workers had a 3.55 times higher risk of being diagnosed T2DM compared to non-shift workers (OR=3.55, 95%CI: 1.026, 12.263). The risk varied across different shift patterns, and the three-shift two-rotation system showed the highest risk (OR=4.17, 95%CI: 1.921, 9.035), followed by the two-shift system (OR=2.94, 95%CI: 2.016, 4.281) and four-shift three-rotation system (OR=2.66, 95%CI: 1.611, 6.093). Workers with more than 3 monthly shift days had a 2.74-fold increased risk (95%CI: 1.658, 4.512) compared to non-shift workers. Additionally, working more than 8 h daily (OR=1.74, 95%CI: 1.185, 2.562) and having more than 20 years of service (OR=2.51, 95%CI: 1.581, 3.976) were both significantly associated with a higher T2DM risk. The trend tests revealed that each incremental increase in monthly shift days and length of service elevated T2DM risk by 2.61 times (95%CI: 1.813, 3.765) and 1.49 times (95%CI: 1.147, 1.931), respectively (P<0.05). Conclusion Shift work is an independent risk factor for T2DM, with three-shift two-rotation system posing the highest risk. Shift frequency, daily working hours, and length of service are all significant factors affecting the risk of T2DM. These findings support industry-specific shift policy reform and targeted glucose monitoring and health interventions are recommended for workers engaged in high-risk shift patterns (e.g., three-shift two-rotation system, frequent shifts) and those with prolonged shift work history (>20 years).
4.Influence of chronic psychological stress during pregnancy on intestinal flora and eczema incidence of offspring rats
Chunyan WANG ; Ying GAO ; Deguang YANG ; Rui WANG ; Hongyu LI ; Ye LI ; Can LIU ; Suzhen GUAN
Journal of Environmental and Occupational Medicine 2025;42(8):962-970
Background Prenatal chronic psychological stress may increase the risk of allergic diseases in children, and eczema is the most common allergic disease in children, the pathogenesis of which is not yet fully understood. Objective To preliminarily clarify the changes in offspring intestinal flora after chronic stress exposure during pregnancy in rats that increases offspring immune imbalance and eczema susceptibility. Methods Thirty SPF-grade adult female SD rats were selected and randomly divided into a model group and a control group (n=15). Sixteen male rats were randomly divided into a model mating group and a control mating group (n=8). A 28-day chronic unpredictable mild stress (CUMS) model during pregnancy was established. On the 7th day of stress, male and female rats were caged in a ratio of 3:1. Blood samples were collected from female rats in each group via angular vein on the 1st day before stress, and on the 7th, 14th, 21st, and 28th days after stress. The content of plasma corticosterone during pregnancy was determined by enzyme-linked immunosorbent assay (ELISA). For the offspring rats, an eczema model was constructed using 2,4-dinitrochlorobenzene (DNCB). The number of scratching times of the offspring rats within 5 min was recorded. The offspring rats were divided into 4 groups: DNCB-CUMS group (MM), DNCB-control group (MC), solvent control-CUMS group (CM), and blank control group (CC), with 8 rats in each group. The eczema was induced once every 3 days, and the induction period was 12 d. The expression level of immunoglobulin E (IgE) in the serum of offspring rats after the eczema induction experiment were determined by ELISA. The concentrations of tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-2 (IL-2), interleukin-4 (IL-4), and interleukin-13 (IL-13) in the serum were quantified by multi-parameter flow cytometry. The composition and abundance of intestinal microbiota in the feces of offspring rats were detected by 16S rRNA high-throughput sequencing technology. Results The plasma corticosterone concentrations in the model group were higher than those in the control group on the 7th and 21st days of stress (P<0.05). On the 14th and 21st days of stress, the 1% sucrose preference percentages of female rats in the model group were lower than that in the control group. On the 7th, 14th, and 21st days of stress, the horizontal movement scores of female rats in the model group and the vertical movement scores on the 7th and 14th days were lower than those in the control group (P<0.05). After 6, 9, and 12 d of model building, the scratching frequencies in the MC group and MM group were significantly higher than those in the CC group and CM group (P<0.05). Moreover, there were differences in the contents of cytokines including IFN-γ, IL-2, TNF-α, IL-4, IL-13, and IgE among the offspring rat groups (P<0.05). The CM group and MM group led to an increase in the contents of TNF-α, IL-4, IL-13, and IgE cytokines (P<0.05), while the MM group caused a decrease in the contents of IFN-γ and IL-2 (P<0.05). After the eczema induction experiment, the α-diversity analysis showed that the Simpson index and Shannon index in the CM were higher than those in the CC (P<0.05), indicating that CUMS during the pregnancy of female rats could increase the species abundance of their offspring. The abundances of Prevotella and Lactobacillus in the CM group decreased (P<0.05). Conclusion Intestinal dysbiosis in offspring due to chronic prenatal psychological stress, which may be one of the mechanisms linking maternal stress to immune imbalance and increased susceptibility to eczema in offspring.
5.Construction of predictive model for pregnancy-related anxiety risk in pregnant women based on LASSO regression
Ye LI ; Rui WANG ; Jiashu ZHU ; Shuqin MA ; Suzhen GUAN
Journal of Environmental and Occupational Medicine 2023;40(8):910-917
Background Pregnancy-related anxiety has a negative impact on the physical and mental health of pregnant women and the normal growth and development of the fetus. Establishing prediction models for pregnancy-related anxiety to screen associated predictive factors may provide important opportunities for prenatal intervention. Objective To establish a prediction model of pregnancy-related anxiety risk of pregnant women. Methods From January to July 2021, a questionnaire survey on pregnancy-related anxiety and predictors was conducted among pregnant women having routine prenatal check-ups provided by an obstetrics clinic of a tertiary grade A hospital in Ningxia. The socio-demographic characteristics of the subjects were collected, and the pregnant women were evaluated by the Life Event Scale (LES), Perceived Social Support Scale (PSSS), Family APGAR Index (APGAR), and Pregnancy-related Anxiety Questionnaire (PAQ). R 4.2.0 software was used to fit all selected variables by least absolute shrinkage and selection operator (LASSO) regression to identify predictors of pregnancy-related anxiety in the second and third trimesters. On the basis of logistic regression analysis, prediction models of pregnancy-related anxiety in the second and third trimesters were constructed, and the model nomogram and receiver operating characteristic curve (ROC) were drawn. The prediction effect of the model was evaluated by area under the curve (AUC). A calibration chart was drawn to evaluate the calibration of the model. Results A total of 1500 questionnaires were distributed, and 1448 valid questionnaires were recovered, with an effective rate of 96.53%. Among the 1448 pregnant women, the overall positive rate of pregnancy-related anxiety was 28.80% (417/1448), and the positive rates in the second and third trimesters were 29.21% (276/935) and 27.49% (141/513), respectively. The predictors entering the the second trimester model were age of marriage, family care, social support, family expectations for the fetus, physical condition during pregnancy, and whether experiencing life stressful events during pregnancy. The predictors entering the the third trimester model were pregnancy intention, physical discomfort, and whether experiencing life stress during pregnancy. A risk prediction model of pregnancy-related anxiety for the second trimester was established: risk of pregnancy-related anxiety=−0.07× marriage age +0.12× family care −0.03× social support −0.65× family expectation of fetal sex +0.42× physical condition during pregnancy +0.47× whether experiencing life stressful events during pregnancy. A risk prediction model of pregnancy-related anxiety for the third trimester was established: risk of pregnancy-related anxiety=−5.69+0.82× pregnancy intention +1.06× physical discomfort +0.94× whether experiencing life stressful events during pregnancy. The ROC curves of the two models were drawn. The AUC of the second trimester model was 0.71, and the AUC of related validation model was 0.68. The AUC of the third trimester model was 0.72, and the AUC of related validation model was 0.66. Conclusion The risk prediction models of pregnancy-related anxiety constructed based on LASSO regression and logistic regression have good prediction ability, and they suggest that pregnant women in the second trimester with short marriage age, high family care, low social support, family expectations for fetal sex, average physical condition, and experiencing life stress during pregnancy, and pregnant women in the third trimester with spontaneous pregnant intention, unintended pregnancy, physical discomfort, and experiencing life stress during pregnancy are high-risk groups for pregnancy-related anxiety.
6.Association between stressful life events during pregnancy and adverse pregnancy outcomes: a review
Journal of Preventive Medicine 2023;35(7):587-590
Improving the quality of newborns is a health development strategy, which has attracted global attention. Adverse pregnancy outcomes, including preterm birth, low birth weight and small for gestational age, are major causes of perinatal mortality and disability. Based on review of international and national publications pertaining to associations between stressful life events during pregnancy and adverse pregnancy outcomes from 2007 to 2023, this review summarizes the correlation between stressful life events during pregnancy and adverse pregnancy outcomes, including preterm birth, low birth weight and small for gestational age, and describes the underlying biological mechanisms. Previous studies have demonstrated the associations between maternal stressful life events during pregnancy and adverse pregnancy outcomes, and the underlying mechanisms mainly include neuroendocrine regulation, inflammation and microbiota pathways; however, the exact mechanisms remain unclear until now. Further studies to identify the critical window period for the association between stressful life events and adverse pregnancy outcomes, and unravel the pathogenesis of adverse pregnancy outcomes are warranted, so as to provide insights into reduction of adverse pregnancy outcomes.
7.Application of CNV-seq and chromosomal karyotyping in the prenatal diagnosis for carriers of balanced translocations.
Suzhen QU ; Panlai SHI ; Tianyuan ZHANG ; Zhi GAO ; Hongying GUAN ; Xiangdong KONG
Chinese Journal of Medical Genetics 2022;39(4):366-369
OBJECTIVE:
To assess the value of copy number variation sequencing (CNV-seq) and karyotyping in the prenatal diagnosis for carriers of balanced translocations.
METHODS:
Clinical records of 135 amniocentesis samples of balanced translocation carriers undergoing simultaneous CNV-seq and karyotyping were analyzed. Chromosomal aberrations were defined as those can definitely lead to birth defects definitely, which included chromosomal numerical abnormality, large deletion/duplication and pathogenic copy number variations (pCNVs).
RESULTS:
The detection rates for karyotyping and CNV-seq were 4.44% (6/135) and 5.93% (8/135) respectively, and the latter had a detection rate of 1.48(2/135) higher than the former. A total of 68 fetal chromosomal translocations were detected by karyotying analysis.
CONCLUSION
For couples carrying a balanced translocation, simultaneous CNV-seq and karyotyping is conducive to the detection of fetal chromosomal abnormalities and genetic counseling.
Chromosome Aberrations
;
Chromosome Disorders/genetics*
;
DNA Copy Number Variations
;
Female
;
Humans
;
Karyotyping
;
Pregnancy
;
Prenatal Diagnosis
;
Translocation, Genetic
8.Effects of chronic stress during pregnancy on depression-like behavior and methylation of imprinted gene IGF-2/H19 in female offspring rats
Ye LI ; Shuqin MA ; Xiaohui CHEN ; Hongya LIU ; Rui WANG ; Jiashu ZHU ; Suzhen GUAN
Chinese Journal of Behavioral Medicine and Brain Science 2022;31(12):1057-1065
Objective:To investigate the effects of chronic stress during pregnancy on depressive behavior and DNA methylation of insulin-like growth factor-2 ( IGF-2 )/long non-coding RNA ( lncRNA ) H19 in hippocampus of female offspring rats.Methods:A total of 32 SPF female SD rats were divided into model group and control group according to the random number table. The rats in the model group were treated with chronic unpredictable mild stress (CUMS) to establish the depression model, and the rats in the control group were fed normally.On the 7th day of stress stimulation, all female rats mated with male rats. One day before stress stimulation and 1, 7, 14, 21, 28 days after stress stimulation, blood samples were collected from the inner canthus vein of the rats to determine the plasma corticosterone concentration. Eight female pups were randomly selected from each group on postnatal day 28(PND28) and postnatal day 42 (PND42). Plasma corticosterone concentration was measured after angular vein blood collection. At PND42, the depression-like behavior of female pups in the two groups was measured by sucrose preference test, tail suspension test and forced swimming test. The expression of IGF-2/H19 and related transferases in hippocampus of offspring rats was detected by RT-PCR and Western blot. Methyl target technology was used to capture and sequence 19 CpG sites of IGF-2 differentially methylated region(DMR) fragment 2, 8 CpG sites in H19 imprinting control region (ICR) fragment 1 and 15 CpG sites in H19-ICR fragment 2, and calculate the methylation level of each CpG site. SPSS 26.0 was used for statistical analysis of relevant data by repeated measurement ANOVA, t test and non-parametric test. Results:(1) The data of plasma corticosterone content of the two groups of female rats at different times were analyzed by repeated measurement variance.The results showed that the the interaction effect between time and group was not significant ( F=2.997, P=0.066), and the main effect of time was significant ( F=4.44, P=0.010). The main effect of group was significant ( F=41.40, P=0.001). According to the independent effect analysis of factors between groups, on the 14th, 21st, and 28th days of stress, the plasma corticosterone concentration of the model group was higher than that of the control group (all P<0.001). (2) In the sucrose preference test, the total liquid consumption (11.10(10.38, 11.58) mL, 13.55(12.00, 15.77) mL, Z=-3.055, P=0.002), 1% sucrose water consumption ((5.50±1.30) mL, (8.56±2.04) mL, t=-3.582, P=0.003) and 1% sucrose preference percentage ( (51.35±8.69) %, (62.11±8.05) %, t=-2.576, P=0.022) of female pups in the model group were significantly lower than those in the control group. (3) The duration of immobility in tail suspension test ((126.95±39.89) s, (54.30±25.00) s, t=4.375, P=0.001) and forced swimming test ((7.97±6.66) s, (1.85±2.12) s, t=2.478, P=0.037) of female offspring in the model group were longer than those in the control group. (4) The expression of IGF-2 mRNA ((0.46±0.24), (1.00±0.00), t=3.821, P=0.019) and H19 mRNA ((0.60±0.25), (1.00±0.00), t=3.574, P=0.007) in hippocampus of female pups in the model group were lower than those of control group. The relative expression of IGF-2 protein in female offspring of model group was lower than that in control group ((0.77±0.04), (1.00±0.00), t=9.876, P=0.01). The relative expression of CCTC-binding factor (CTCF) mRNA ((1.29±0.12), (1.00±0.00), t=-4.850, P=0.003) and protein ((1.90±0.28), (1.00±0.00), t=-5.513, P=0.005) were higher than those in the control group. (5) The methylation levels of three CpG sites in the IGF-2 DMR region of female offspring in the model group were lower than those in the control group ( t=-3.21, -3.00, -3.34, all P<0.05), located at chr1215831028, chr1215831055 and chr1215831205, respectively. The methylation level of IGF-2 DMR fragment was lower than that of the control group ( t=-3.453, P=0.048). The relative expression levels of DNMT3A mRNA ( t=5.102, P=0.002), DNMT3A ( t=10.213, P<0.001) and DNMT3B ( t=4.169, P=0.014) in female offspring of the model group were lower than those in the control group. Conclusion:Chronic stress during pregnancy causes depression and despair in female offspring mice, and the mechanism may be related to the decrease of methylation level of imprinted gene IGF-2 DMR caused by the decrease of methyltransferase expression.
9.Mechanism of miR-21 targeting Smad7 in pulmonary fibrosis of A549 cells induced by beryllium sulfate
Faqiu QI ; Xiaohui CHEN ; Hongya LIU ; Feng ZHAO ; Youjuan FU ; Suzhen GUAN ; Kai WANG
Journal of Environmental and Occupational Medicine 2022;39(2):206-211
Background The pathogenesis of beryllium-induced pulmonary fibrosis is unknown and there is no specific treatment for the disease as yet. MicroRNA (miRNA) may play a role in the process of beryllium-induced pulmonary fibrosis. Objective To construct a microRNA-21 (miR-21) interfering cell line, and to investigate the effect of miR-21 on beryllium sulfate (BeSO4)-induced fibrosis in human lung adenocarcinoma alveolar basal epithelial cells (A549 cells) and its potential mechanism. Methods The miR-21 target genes were predicted by the online database miRBase and verified by experiments using dual luciferase reporter gene. After transfecting A549 with miR-21interference lentivirus, puromycin was used to select a stable cell line. An in vitro model of pulmonary fibrosis was established using BeSO4 infecting A549 cells with a concentration of 10 μmol·L−1 and an exposure time of 48 h. Then the treated cells were divided into control group, model group, miR-21 interference group, and miR-21 interference control group. Real-time fluorescent quantitative PCR (RT-qPCR) was used to detect the relative expression level of miR-21 gene. Western blotting was used to detect the relative expression levels of TGF-β1/Smads pathway related proteins [Smad2, Smad3, p-Smad2, p-Smad3, Smad7, and transforming growth factor-β1 (TGF-β1)], myofibrosis cell marker α-smooth muscle actin (α-SMA), andextracellular matrix collagen-I (COL-I) and collagen-Ⅲ (COL-Ⅲ). Results The miRBase predicted that miR-21 had a binding site with Smad7, and the results of the dual luciferase reporter gene experiment showed that the target gene of miR-21 was Smad7. The construction of miR-21 interfered with A549 cell line was successful. Compared with the control group, the relative expression of miR-21 gene in the model group increased by 97.57%; the relative expression of Smad7 protein in the model group decreased by 15.48%; the relative protein expression of Smad2, Smad3, p-Smad2, p-Smad3, TGF-β1, α-SMA, COL-I, and COL-Ⅲ increased by 13.55%, 35.72%, 18.35%, 35.75%, 25.52%, 31.58%, 24.61%, and 11.66% respectively (P<0.05). Compared with the interference control group, the miR-21 gene expression level in the interference group decreased by 28.96%; the relative expression of Smad7 protein increased by 19.07%; the relative protein expression of Smad2, Smad3, p-Smad2, p-Smad3, TGF-β1, α-SMA, COL-I, and COL-Ⅲ decreased by 8.01%, 19.95%, 14.56%, 19.37%, 11.95%, 10.96%, 18.81%, and 31.36% repectively (P<0.05). There was no statistically significant difference in the gene abd protein expression levels of each gene between the model group and the interference control group (P>0.05). Conclusion In an in vitro model of pulmonary fibrosis induced by beryllium compounds, miR-21 may promote fibrosis by targeting Smad7 to regulate the TGF-β1/Smad signaling pathway.
10.Meta-analysis of effects of long-term exposure to PM2.5 on C-reactive protein levels
Yifei LIU ; Suzhen GUAN ; Haiming XU ; Na ZHANG ; Min HUANG ; Zhihong LIU
Journal of Environmental and Occupational Medicine 2022;39(12):1398-1403
Background Fine particulate matter (PM2.5) is a serious air pollutant associated with elevated levels of C-reactive protein (CRP), an inflammatory indicator. Objective To assess the potential impacts of long-term exposure to PM2.5 on CRP levels based on previous epidemiological studies. Methods PubMed, Embase, Web of Science, CNKI, and Wanfang databases were searched to screen the cohort studies published from January 1, 2000 to January 1, 2022 on the effects of long-term exposure to PM2.5 on CRP levels. "Fine Particulate Matter", "PM2.5", "Particulate Air Pollutants", "Ambient Particulate Matter", "CRP", "C-reactive Protein", and "High Sensitivity C-reactive Protein" in English or Chinese were the key words used in the search. The percentage change in CRP level per 10 μg·m−3 increase in PM2.5 concentration in each study was extracted, followed by meta-analysis, subgroup analysis, and sensitivity analysis. Results A total of 1241 articles were retrieved, and 7 articles were included. Random-effects models were used to merge the included data, and it was found that the percentage of CRP level increased by 10.41% (95%CI: 2.24%-18.57%, P<0.05), when PM2.5 concentration increased by 10 μg·m−3, І2=84.2%. The subgroup analysis conducted with grouping based on the annual mean concentration of PM2.5 long-term exposure showed that the intra-group heterogeneity was significantly reduced in the <15 μg·m−3 and the 15- μg·m−3 groups, and the subgroup forest analysis showed differences between the two groups. The results of sensitivity analysis showed that there was a high degree of heterogeneity among the 7 studies, and the 2 papers with the highest annual average PM2.5 concentration were the sources of heterogeneity. The Egger test and the funnel plot indicated that no obvious publication bias was found. Conclusion Long-term exposure to PM2.5 can raise levels of CRP in human body.


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