1.Unlocking therapeutic potential: Exploring nuclear receptors in brain cancer treatment.
Sujitha JAYAPRAKASH ; Hiu Yan LAM ; Ravichandran VISHWA ; Bandari BHARATHWAJCHETTY ; Kenneth C-H YAP ; Mohammed S ALQAHTANI ; Mohamed ABBAS ; Gautam SETHI ; Alan Prem KUMAR ; Ajaikumar B KUNNUMAKKARA
Chinese Medical Journal 2025;138(21):2722-2752
Brain cancer remains among the most lethal malignancies worldwide, with approximately 321,476 new cases and 248,305 deaths reported globally in 2022. The treatment of malignant brain tumors presents substantial clinical challenges, primarily due to their resistance to standard therapeutic approaches. Despite decades of intensive research, effective treatment strategies for brain cancer are still lacking. Nuclear receptors (NRs), a superfamily of ligand-activated transcription factors, regulate a broad range of physiological processes including metabolism, immunity, stress response, reproduction, and cellular differentiation. Increasing evidence highlights the involvement of NRs in oncogenesis, with several members demonstrating altered expression and function in brain tumors. Aberrations in NR signaling, encompassing receptors such as androgen receptors, estrogen receptors, estrogen-related receptors, glucocorticoid receptors, NR subfamily 4 group A, NR subfamily 1 group D member 2, NR subfamily 5 group A member 2, NR subfamily 2 group C member 2, liver X receptors, peroxisome-proliferator activated receptors, progesterone receptors, retinoic acid receptors, NR subfamily 2 group E member 1, thyroid hormone receptors, vitamin D receptors, and retinoid X receptors, have been implicated in promoting hallmark malignant phenotypes, including enhanced survival, proliferation, invasion, migration, metastasis, and resistance to therapy. This review aims to explore the roles of key NRs in brain cancer, with an emphasis on their prognostic significance, and to evaluate the therapeutic potential of targeting these receptors using selective agonists or antagonists.
Humans
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Brain Neoplasms/drug therapy*
;
Receptors, Cytoplasmic and Nuclear/metabolism*
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Animals
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Signal Transduction/physiology*
4.Human leukocyte antigen polymorphism of HIV infected persons without disease progress for long-term in Henan province, 2011-2016.
X J XUE ; J Z YAN ; D CHENG ; C H LIU ; J LIU ; Z LIU ; S A TIAN ; D Y SUN ; B W ZHANG ; Z WANG
Chinese Journal of Epidemiology 2019;40(1):89-92
Objective: To understand the disease progression and human leukocyte antigen (HLA) gene polymorphism of HIV-infected persons without disease progress for long term, also known as long-term non-progressors (LTNPs), in Henan province. Methods: A retrospective study was conducted in 48 LTNPs with complete detection and follow-up information during 2011-2016 in Henan. Changes of CD(4)(+)T cells counts (CD(4)) and viral load (VL) during follow-up period were discussed. Polymerase chain reaction-sequence-specific oligonucleotide probe (PCR-SSOP) was used for the analyses of HLA-A, HLA-B and HLA-DRB1 alleles between LTNPs and healthy controls. Results: From 2011 to 2016, forty-eight LTNPs showed a decrease of the quartile (P(25)-P(75)) of CD(4) from 601.00 (488.50-708.72)/μl to 494.00 (367.00-672.00)/μl, and the difference was significant (P<0.05). The increase of the quartile (P(25)-P(75)) of log(10)VL from 3.40 (2.87-3.97) to 3.48 (2.60-4.37), but the difference was not significant (P>0.05). HLA polymorphism analysis revealed that HLA-B*13:02 and HLA-B*40:06 were more common in LTNPs (P<0.05), while HLA-B*46:01 and HLA-DRB1*09:01 were more common in healthy controls (P<0.05). Conclusions: The CD(4) of LTNPs in Henan showed a downward trend year by year. HLA-B*13:02 and B*40:06 might be associated with delayed disease progression for HIV infected persons in Henan.
Adult
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Alleles
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Asian People/genetics*
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China
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Disease Progression
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Female
;
HIV
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HIV Infections/virology*
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HIV-1/immunology*
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HLA-B Antigens/genetics*
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Humans
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Middle Aged
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Polymorphism, Genetic
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Retrospective Studies
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Viral Load
5.Exposure to bisphenol A during maternal pregnancy and the emotional and behavioral impact on their preschool children.
X CHEN ; H H BAO ; W K WU ; S Q YAN ; J SHENG ; Y Y XU ; C L GU ; K HUANG ; H CAO ; P Y SU ; F B TAO ; J H HAO
Chinese Journal of Epidemiology 2018;39(2):188-193
Objective: To explore the long-term effects of maternal pregnancy bisphenol A (BPA) exposure on emotional and behavioral problems appeared in their preschool children. Methods: The study sample was a subset of the China-Anhui Birth Cohort Study (C-ABCS). A unified questionnaire was used to collect basic information on both pregnant women and their children. Free BPA concentration in maternal serum was determined by high-performance liquid chromatographytandem mass spectrometry (HPLC-MS/MS). The parent-report version of the Strengths and Difficulties Questionnaire (SDQ) was used to estimate the emotional and behavioral problems in preschool children. A total of 1 713 pairs of mothers and children were included in this study. Association between BPA exposure during pregnancy and the emotional and behavioral problems in preschool children was evaluated with multinomial logistic regression model. Results: Prevalence rates in 1 713 preschool children appeared as: 6.48% of emotional problems, 8.11% for conduct problems, 8.35% for hyperactivity/inattention, 2.86% for peer problems, 11.38% for prosocial behaviors and 7.94% for total difficulties. Subjects were divided according to the degrees of exposure and the results showed as: low exposure group (≤0.120 ng/ml), medium exposure group (0.120
Benzhydryl Compounds/toxicity*
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Child Behavior Disorders/etiology*
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Child, Preschool
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China/epidemiology*
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Cohort Studies
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Emotions/physiology*
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Environmental Exposure
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Environmental Pollutants
;
Female
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Gas Chromatography-Mass Spectrometry
;
Humans
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Male
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Maternal Exposure
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Mothers
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Phenols/toxicity*
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Pregnancy
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Prenatal Exposure Delayed Effects
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Prevalence
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Risk Factors
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Surveys and Questionnaires
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Tandem Mass Spectrometry
6.Willingness and influencing factors related to "centralized slaughtering, fresh poultry listing and marketing" strategy among the household chefs in Guangzhou.
W H LIU ; Y MA ; J Y LU ; H C YAN ; J H ZHOU ; X L LIAO ; J H ZENG ; W Q LIN ; D WU ; Z B ZHANG ; Z C YANG ; Z Q CHEN ; J D CHEN ; T G LI
Chinese Journal of Epidemiology 2018;39(2):204-207
Objective: To study the willingness and influence factors related to "centralized slaughtering, fresh poultry listing and marketing" strategy, among the household chefs, and provide reference for government to adjust and optimize the strategy on avian influenza prevention. Methods: According to the geographical characteristics and regional functions, 6 'monitoring stations' were selected from 12 residential districts of Guangzhou, respectively. Another 21 meat markets which selling live poultry, were selected in each station and 5 household chefs of each market were invited to attend a face to face interview. Basic information, personal cognitive, willingness and influencing factors to the policy were under study. Univariate and multivariate logistic regression methods were used. Results: A total of 664 household chefs underwent the survey and results showed that the rate of support to the "centralized slaughtering, fresh poultry listing and marketing" strategy was 44.6% (296/664). Results from the multi-factor logistic regression showed that those household chefs who were males (OR=1.618, 95% CI: 1.156-2.264, P=0.005), having received higher education (OR=1.814, 95% CI: 1.296-2.539, P=0.001), or believing that the existence of live poultry stalls was related to the transmission of avian influenza (OR=1.918, 95% CI: 1.341-2.743, P<0.001) were factors at higher risk. These household chefs also intended to avoid the use of live poultry stalls (OR=1.666, 95%CI: 1.203-2.309, P=0.002) and accept the "centralized slaughtering, fresh poultry listing and marketing" strategy. Conclusion: Detailed study on this subject and, setting up pilot project in some areas as well as prioritizing the education programs for household chefs seemed helpful to the implementation of the 'freezing-fresh poultry' policy.
Animals
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Attitude to Health
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China
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Humans
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Influenza A Virus, H7N9 Subtype
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Influenza in Birds
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Influenza, Human/prevention & control*
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Male
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Marketing
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Meat-Packing Industry
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Multivariate Analysis
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Pilot Projects
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Poultry/virology*
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Surveys and Questionnaires
7.Associations of obesity and physical activity with cognition in people aged 50 and above in Shanghai.
Z Z HUANG ; Y C ZHANG ; Y ZHENG ; Y F GUO ; Y RUAN ; S Y SUN ; Y SHI ; S N GAO ; J H YE ; Y J YAN ; K WU ; R F XU ; F WU
Chinese Journal of Epidemiology 2018;39(3):273-279
Objective: To investigate the associations of obesity and physical activity with cognition in the elderly. Methods: A cross-sectional survey was conducted from October 2009 to June 2010 among people aged ≥50 years selected through multistage random cluster sampling in Shanghai. The subjects' body weight, body height, waist circumference and hip circumference were measured to calculate body mass index (BMI) and waist-hip ratio (WHR), and the data on self-reported physical activity level were collected through questionnaire survey. A comprehensive battery of cognitive tests was conducted to assess subjects' cognitive functions, including verbal recall, forward digit span (FDS), backward digit span (BDS), and verbal fluency (VF). General linear model was used to examine the associations of BMI, WHR and physical activity with cognition. Results: A total of 7 913 participants were included, with a median age of 60 years. Age, sex, education level, income level, BMI, WHR and physical activity level were significantly associated with cognitive scores in univariate analysis. After adjusted for age, sex, education level and income level, BMI was no longer significantly associated with cognitive scores in all cognitive functions (all P>0.01). WHR was significantly associated with VF score (P<0.01). Abdominally obese participants had lower VF score than non-abdominally obese participants (P<0.01). Physical activity level was significantly associated with all cognitive functions (P<0.01). Compared with participants with moderate physical activity level, participants with low physical activity level had lower scores in all cognitive functions (P<0.01). Conclusion: Abdominal obesity and low physical activity level were negatively associated with cognition level in the elderly, suggesting that waist circumference control and physical activity might help maintain cognition in the elderly.
Aged
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Body Height
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Body Mass Index
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Body Weight
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China
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Cognition/physiology*
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Cross-Sectional Studies
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Exercise
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Humans
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Middle Aged
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Obesity
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Surveys and Questionnaires
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Waist Circumference
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Waist-Hip Ratio
8.Potential interaction effect on attention-deficit/hyperactivity disorder between mother's educational level and preschoolers' dietary pattern.
S Q YAN ; H CAO ; C L GU ; G P GAO ; L L NI ; H H TAO ; T SHAO ; Y Q XU ; F B TAO
Chinese Journal of Epidemiology 2018;39(4):464-468
Objective: To explore the interaction effect between mother's educational level and preschoolers' dietary pattern on attention-deficit/hyperactivity disorder (ADHD). Methods: In 2014, there were 16 439 children aged 3-6 years old from 91 kindergartens in Ma'anshan municipality of China. A semi-quantitative food frequency questionnaire and the 10-item Chinese version of the Conners' Abbreviated Symptom Questionnaire (C-ASQ) were administered to assess the usual dietary intake and symptoms on ADHD. Social-demographic information was collected through questionnaires. Unconditional logistic regression was used to analyze the multiplication interaction effect between mother's educational level and preschoolers' dietary pattern on ADHD. Excel software was used to analyze the additive interaction effect of mother's educational level and preschoolers'dietary pattern on ADHD. Results: Results showed that factors as: mother's low educational level[aOR=1.31 (1.13-1.52)], scores related to preschoolers in the top quintile of "food processing" [aOR=1.31 (1.16-1.48)] and "snack" [aOR=1.45 (1.29-1.63)]patterns showed greater odds while preschoolers in the top quintile of "vegetarian" [aOR=0.80 (0.71-0.90)]showed less odds for having ADHD symptoms. Both multiplication and additive interactions were observed between mothers with less education. The processed dietary patterns (OR=1.17, 95%CI: 1.11-1.25), relative excess risk of interaction (RERI), attributable proportion (AP) and the interaction index (SI) appeared as 0.21, 0.13 and 1.47, respectively. Multiplication interaction was observed between levels of mother's low education and the snack dietary pattern (OR=1.21, 95%CI: 1.14-1.29), with RERI, AP and SI as 0.49, 0.26 and 2.36, respectively. However, neither multiplication interaction or additive interaction was noticed between levels of mother's low education and the vegetarian dietary pattern (OR=0.97, 95%CI: 0.92-1.03), with RERI, AP and SI as 0.09, 0.05 and 1.15, respectively. Conclusions: Levels of mother's low education presented a risk factor for ADHD symptoms in preschool children. Both multiplication interaction and additive interaction were observed between mother's low education levels and the processed dietary pattern. Multiplication interaction was noticed between mother's education levels and the snack dietary pattern but not with the vegetarian dietary pattern.
Attention Deficit Disorder with Hyperactivity/epidemiology*
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Child
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Child Nutritional Physiological Phenomena
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Child, Preschool
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China
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Diet
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Educational Status
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Feeding Behavior
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Female
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Humans
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Logistic Models
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Mothers
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Risk Factors
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Surveys and Questionnaires
9.Developmental characteristics of circadian rhythms in hypothalamic-pituitary-adrenal axis during puberty.
X N DUAN ; S Q YAN ; S M WANG ; J J HU ; J FANG ; C GONG ; Y H WAN ; P Y SU ; F B TAO ; Y SUN
Chinese Journal of Epidemiology 2018;39(8):1086-1090
Objective: To explore the developmental characteristics of circadian rhythms in hypothalamus-pituitary-adrenal (HPA) axis during puberty. Methods: A total of 1 070 students from Grade 2-3 in 3 primary schools in Ma'anshan city, Anhui province, were selected for physical examination and circadian rhythm of HPA axis checked from 2015 to 2017. Saliva samples were collected at each of the following three time points: immediately upon wakening, 30 minutes after wakening and bedtime, with the index of circadian rhythm of HPA axis calculated, which including cortisol awake response (CAR), cortisol in puberty priming and diurnal cortisol slope (DCS). Testicular volume, palpation and visual inspection of breast development were used to assess the state of purbety development on boys and girls. Information on gender, date of birth, time to fall asleep, wake-up time and weekly physical activity were gathered through questionnaire survey. Non-parametric test was used to compare the differences of baseline, follow-up period and different adolescent developmental processes of each index on circadian rhythm of HPA axis. Results: During the period of follow-up program and comparing with the continuous undeveloped group, CAR and the changes of CAR showed significantly increase, both in the puberty priming group and continuous development group, with statistically significant differences (CAR: Z=8.551, 4.680, respectively; P<0.01; the changes of CAR: Z=4.079, 2.700, respectively, P<0.01). There were no significant differences noticed in CAR and the changes of CAR between puberty priming group or continuous development group. The area under the curve (AUC) of cortisol in puberty priming group was slightly higher than that in the persistent undeveloped group (Z=2.591, P=0.010). Both the changes of daily cortisol slope (DCS) in puberty priming group and continuing developed group decreased significantly, when comparing with those in continuous undeveloped group (Z=-2.450, Z=-2.151; all P<0.05). There was no significant difference noticed in the changes of cortisol in puberty priming and DCS between different puberty development stages (the changes of AUC: χ(2)=2.747, P=0.253; DCS: χ(2)=4.554, P=0.032). Conclusions: The indexes of circadian rhythm of HPA axis were associated with the development of puberty. Both the cortisol awakening response and the total amount of diurnal cortisol secretion showed an increase, along with the puberty development. The change of diurnal cortisol slope declined with the development of puberty.
Adolescent
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Area Under Curve
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Circadian Rhythm
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Female
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Humans
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Hydrocortisone
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Hypothalamo-Hypophyseal System
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Male
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Pituitary-Adrenal System
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Pregnancy
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Saliva
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Sexual Maturation/physiology*
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Surveys and Questionnaires
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Wakefulness
10.Study on the relationship of thallium exposure and outcomes of births.
J QI ; C M LIANG ; S Q YAN ; Z J LI ; J LI ; K HUANG ; H Y XIANG ; Y R TAO ; J H HAO ; S L TONG ; F B TAO
Chinese Journal of Epidemiology 2018;39(8):1112-1116
Objective: To investigate the relationship of thallium exposure and outcomes of births. Methods: A total of 3 236 mothers who had visited in Ma'anshan Maternal and Child Health-Care Hospital between May 2013 and September 2014 were included in this study and their thallium concentrations measured from samples of maternal and umbilical cord blood by inductively coupled plasma mass spectrometry. The results were correlated and evaluated with birth outcomes of the infants, using the multiple linear regression method. Results: The median (P(25)-P(75)) of thallium levels in first trimester, second trimester and umbilical cord blood were 61.7 (50.8-77.0), 60.3 (50.8-75.2) and 38.5 (33.6-44.1) ng/L, respectively. After adjustment for potential confounders, the thallium levels showed an inversely significant association with birth head circumference (unstandardized β coefficient=-0.41, 95%CI: -0.76- -0.06) in the first trimester blood, and associated with reduced birth length (unstandardized β coefficient=-0.65, 95%CI: -1.25- -0.05) in umbilical cord blood. However, there appeared no significantly associations with birth weight, length and head circumference (P>0.05) in second trimester. On stratification by sex, in girls but not in boys, the thallium levels were adversely associated with birth head circumference (unstandardized β coefficient=-0.53, 95%CI: -1.05--0.01) in the first trimester and were associated with decreased birth weight (unstandardized β coefficient=-277.08, 95%CI: -485.13- -69.03) and length (unstandardized β coefficient=-1.39, 95%CI: -2.26- -0.53) in umbilical cord blood thallium. Conclusions: Thallium exposure appeared a gender difference in newborn birth outcomes. In the first trimester, it was negatively associated with the birth head circumference, in the umbilical cord blood, and reduced birth weight and length in girls.
Adult
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Birth Weight
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Environmental Pollutants/blood*
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Female
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Fetal Blood/metabolism*
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Fetus/metabolism*
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Humans
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Infant, Newborn
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Male
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Maternal Exposure
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Parturition
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Pregnancy
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Pregnancy Outcome/epidemiology*
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Thallium/blood*

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