1.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.
2.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.
3.Research progress in mitochondrial quality control in schizophrenia
Haoran CHU ; Cuicui CUI ; Xianbiao SU ; Hongchang ZHANG ; Jiashu MA ; Houming ZHU ; Ludong BAI ; Ranran LI
Journal of Central South University(Medical Sciences) 2024;49(1):128-134
Mitochondria are the main site of energy metabolism within cells,generating a substantial amount of ATP to supply energy to the human body.Research has shown that alterations in mitochondrial structure and function exist in individuals with schizophrenia,suggesting their potential impact on the onset of psychiatric disorders and clinical treatment efficacy.Therefore,understanding the research progress on the genetic mechanisms,pathological processes,image manifestations of schizophrenia and mitochondrial quality control,and summarizing the relevant evidence of mitochondrial-related targets as potential therapeutic targets for schizophrenia,can provide references for further research.
4.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.
5.Automated proton magnetic resonance spectroscopy imaging guided frameless stereotactic biopsy of intracranial lesions.
Weijie ZHU ; Xiaolei CHEN ; Jiashu ZHANG ; Fangye LI ; Dongdong WU ; Meng ZHANG ; Huaping ZHANG ; Zhijun SONG ; Bainan XU
Chinese Journal of Surgery 2014;52(4):280-284
OBJECTIVETo evaluate the feasibility, reliability and accuracy of the automated magnetic resonance spectroscopy ((1)H-MRS) guided frameless brain biopsy with intraoperative magnetic resonance imaging (iMRI).
METHODSBetween July 2011 and July 2013, a consecutive series of 93 patients were prospectively enrolled. All the patients had intracranial lesions which need biopsy to confirm the diagnosis. Among them, 48 patients were male, 45 patients were female. Their age range from 7 years to 76 years, the median age was 47 years. All patients underwent MRS examination. With MRS automatic fusion technique, the metabolic images were integrated into a standard navigation system (Vario Guide) to guide frameless biopsy. High-field iMRI (1.5 T) was used for target inspection, brain shift correction, and intra-operative exclusion of intra-cerebral hemorrhage and other complications.
RESULTSFor all the 93 patients, (1)H-MRS based metabolic images could be automatically integrated into a standard navigation system and average fusion procedure could be taken 5 minutes 6 seconds. For (1)H-MRS guided stereotactic biopsy of intracranial lesions, the diagnosis yield rate was 94.6% (88/93). Four cases did not get a clear pathological diagnosis, while 1 case did not match the pathological diagnosis result which obtained by following craniotomy. Technical related complication rate was 2.2% (2 cases, intra-cerebral hemorrhage), which were intra-operatively depicted with iMRI, and managed properly. Among them, 1 case with small volume (5 ml) intracerebral hematoma fully recovered 10 days after surgery without second surgical intervention. One case with large volume intracerebral hematoma (32 ml) was depicted with iMRI, followed by craniotomy and hematoma evacuation in the same session. This case had no new or worsened neurologic deficit post-operatively.
CONCLUSIONS(1)H-MRS based metabolic imaging can be automatically integrated into a standard navigation system and used for frameless brain biopsy. The target can be selected according to the metabolic status of the lesion. Hence, the target can be more accurate. And the pathological diagnosis yield rate is higher. With iMRI, the method is safe, and has high clinical efficacy.
Adolescent ; Adult ; Aged ; Biopsy ; methods ; Brain ; pathology ; Brain Neoplasms ; pathology ; Child ; Female ; Humans ; Male ; Middle Aged ; Neuronavigation ; methods ; Prospective Studies ; Proton Magnetic Resonance Spectroscopy ; Stereotaxic Techniques ; Young Adult