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Second-hand smoke (SHS) has been shown to be associated with psychiatric distress in pregnant women spontaneously conceived (SC), but this has never been investigated in pregnant women with assisted reproductive technology (ART) treatment. This study aimed to investigate and compare the associations of SHS with psychiatric distress among SC and ART pregnant women. Participants (1467 SC and 857 ART women) were from the sub-study of Chinese National Birth Cohort (CNBC) in Anhui Province. SHS was assessed by the self-reported questionnaire. The symptoms of depression, anxiety, stress, and poor sleep quality were assessed using CES-D, SAS, CPSS, and PSQI questionnaire. Multivariable linear regression was used to determine the association between SHS and psychiatric distress in each trimester. In SC women, SHS (yes or no) was associated with depression and anxiety symptoms in the 3rd trimester (β = 0.90, 95% CI 0.07-1.73 for depression and β = 1.21, 95% CI 0.39-2.04 for anxiety) and stress symptom and poor sleep quality in both the 2nd and 3rd trimesters (β = 0.85, 95% CI 0.20-1.49 in the 2nd trimester and β = 0.69, 95% CI 0.07-1.32 in the 3rd trimester for stress, and β = 1.32, 95% CI 0.68-1.96 in the 2nd trimester and β = 1.38, 95% CI 0.64-2.11 in the 3rd trimester for poor sleep quality). By contrast, in ART women, SHS was associated with depression and stress symptoms in the 1st trimester (β = 1.97, 95% CI 0.59-3.35 for depression and β = 1.18, 95% CI 0.24-2.12 for stress) and poor sleep quality throughout the pregnancy (β = 0.64, 95% CI 0.22-1.06 in the 1st trimester, β = 0.77, 95% CI 0.35-1.18 in the 2nd trimester, and β = 0.99, 95% CI 0.50-1.48 in the 3rd trimester, respectively). Our findings indicate a universal and detrimental effect of SHS on psychiatric health among both SC and ART pregnant women. However, the SHS impact may be more substantial at the early stage of pregnancy for ART women and at later stages for SC women. This implies the importance of reducing SHS exposure during pregnancy and the necessary to be aware of the difference in the effect of SHS on psychiatric distress between SC and ART women.

Polymorphisms in mitochondrial DNA (mtDNA) have been linked to a range of diseases. Here we investigate the relationship between mtDNA D-loop region polymorphisms, mtDNA haplotype and polycystic ovary syndrome (PCOS), as well as the correlation of D-loop variants and clinical characteristics of PCOS, in a Chinese population. The mtDNA D-loop of whole blood samples from 421 PCOS patients and 409 controls underwent next generation sequencing. The variants G207A (PBH＜0.05), 16036GGins (PBH＜0.05) and 16049Gins (PBH＜0.001) were associated with decreased risk of PCOS. No variants were associated with PCOS, and within the PCOS group, no statistical significance was found between D-loop polymorphisms and clinical characteristics. Patient haplotype was identified from D-loop single nucleotide polymorphisms and analysis suggested that haplotype A15 (P adjusted ＜0.01) was significantly associated with decreased risk of PCOS. In conclusion, mtDNA D-loop alterations and haplotype appear to confer resistance to PCOS in Chinese women.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease and currently has no effective treatment. Mainstream research on the mechanisms and therapeutic targets of AD is focused on the two most important hallmarks, Aβ and Tau, but the results from clinical studies are not encouraging. Abnormal microglial polarization is a clear typical pathological feature in the progression of AD. Microglia can be neuroprotective by degrading and removing Aβ and Tau. However, under AD conditions, microglia transform into a pro-inflammatory phenotype that decreases the phagocytic activity of microglia, damages neurons and promotes the pathology of AD. We previously reported that a miR-146a polymorphism is associated with sporadic AD risk, and the nasal administration of miR-146a mimics reduced cognitive impairment and the main pathological features of AD. However, it is not clear by what mechanism miR-146a resists the pathological process of AD. In this study, we discovered that microglia-specific miR-146a overexpression reduced cognitive deficits in learning and memory, attenuated neuroinflammation, reduced Aβ levels, ameliorated plaque-associated neuritic pathology, and prevented neuronal loss in APP/PS1 transgenic mice. In addition, we found that miR-146a switched the microglial phenotype, reduced pro-inflammatory cytokines and enhanced phagocytic function to protect neurons in vitro and in vivo. Moreover, transcriptional analysis confirmed that miR-146a opposed the pathological process of AD mainly through neuroinflammation-related pathways. In summary, our results provide sufficient evidence for the mechanism by which miR-146a opposes AD and strengthen the conclusion that miR-146a is a promising target for AD and other microglia-related diseases.

Growing evidence indicated that single nucleotide polymorphisms (SNPs) in the apolipoprotein E (APOE) gene are related to increase the risk of many inflammatory-related diseases. However, few genetic studies have associated the APOE gene polymorphism with sepsis. This study was to investigate the clinical relevance of the APOE gene polymorphism in the onset and progression of sepsis. A multicenter case–control association study with a large sample size (601 septic patients and 699 healthy individuals) was conducted. Clinical data showed that the APOEε4 allele was overrepresented among all patients with septic shock (p = 0.031) compared with sepsis subtype, suggesting that APOEε4 allele may associated with increased susceptibility to the progression of sepsis. Moreover, the APOE mRNA levels decreased after lipopolysaccharide (LPS) stimulation in cells in culture. Then 21 healthy individuals to extract PBMC for genotype grouping (APOE4+ group 8; APOE4− group 13) was selected to evaluate the effect on APOE level, and results showed that the expression level of APOE in APOE4+ group and APOE4− group did not differ in mRNA levels after an LPS challenge, but the protein levels in APOE4+ group decreased slower than that in APOE4− group, and this process was accompanied by the upregulation of proinflammatory cytokines. These results provide evidence that the APOEε4 allele might be associated with the development of sepsis and a potential risk factor that can be used in the prognosis of sepsis.

This research aimed to investigate the role of glyoxalase 1 (Glo-1) polymorphisms in the susceptibility of schizophrenia. Using the real-time polymerase chain reaction (PCR) and spectrophotometric assays technology, significant differences in Glo-1 messenger ribonucleic acid (mRNA) expression (P = 3.98 × 10−5) and enzymatic activity (P = 1.40 × 10−6) were found in peripheral blood of first-onset antipsychotic-naïve patients with schizophrenia and controls. The following receiver operating characteristic (ROC) curves analysis showed that Glo-1 could predict the schizophrenia risk (P = 4.75 × 10−6 in mRNA, P = 1.43 × 10−7 in enzymatic activity, respectively). To identify the genetic source of Glo-1 risk in schizophrenia, Glo-1 polymorphisms (rs1781735, rs1130534, rs4746, and rs9470916) were genotyped with SNaPshot technology in 1,069 patients with schizophrenia and 1,023 healthy individuals. Then, the impact of risk polymorphism on the promoter activity, mRNA expression, and enzymatic activity was analyzed. The results revealed significant differences in the distributions of genotype (P = 0.020, false discovery rate (FDR) correction) and allele (P = 0.020, FDR correction) in rs1781735, in which G > T mutation significantly showed reduction in the promoter activity (P = 0.016), mRNA expression, and enzymatic activity (P = 0.001 and P = 0.015, respectively, GG vs. TT, in peripheral blood of patients with schizophrenia) of Glo-1. The expression quantitative trait locus (eQTL) findings were followed up with the resting-state functional magnetic resonance imaging (fMRI) analysis. The TT genotype of rs1781735, associated with lower RNA expression in the brain (P < 0.05), showed decreased neuronal activation in the left middle frontal gyrus in schizophrenia (P < 0.001). In aggregate, this study for the first time demonstrates how the genetic and biochemical basis of Glo-1 polymorphism culminates in the brain function changes associated with increased schizophrenia risk. Thus, establishing a combination of multiple levels of changes ranging from genetic variants, transcription, protein function, and brain function changes is a better predictor of schizophrenia risk.

Autophagy is a basic physiological process maintaining cell renewal, the degradation of dysfunctional organelles, and the clearance of abnormal proteins and has recently been identified as a main mechanism underlying the onset and progression of Alzheimer’s disease (AD). The APOE ɛ4 genotype is the strongest genetic determinant of AD pathogenesis and initiates autophagic flux at different times. This review synthesizes the current knowledge about the potential pathogenic effects of ApoE4 on autophagy and describes its associations with the biological hallmarks of autophagy and AD from a novel perspective. Via a remarkable variety of widely accepted signaling pathway markers, such as mTOR, TFEB, SIRT1, LC3, p62, LAMP1, LAMP2, CTSD, Rabs, and V-ATPase, ApoE isoforms differentially modulate autophagy initiation; membrane expansion, recruitment, and enclosure; autophagosome and lysosome fusion; and lysosomal degradation. Although the precise pathogenic mechanism varies for different genes and proteins, the dysregulation of autophagic flux is a key mechanism on which multiple pathogenic processes converge.

Background Mycoplasma genitalium (MG) causes urogenital tract infections and is associated with reproductive morbidity. Although MG has been reported across many regions and population groups, it is not yet routinely tested for in China. Our study contributes to current research by reporting the prevalence and correlates of MG infection in patients attending a sexually transmitted infection (STI) clinic in Guangdong from Jan 2017-May 2018. Methods Urethral (from 489 men) and endo-cervical (from 189 women) samples, blood samples, and patient histories (via questionnaires) were collected. Doctors clinically diagnosed anogenital warts (GW) during the examination (n = 678). The presence of MG was evaluated using an in-house via polymerase chain reaction protocol. We also tested all participants for herpes simplex virus-2 (HSV-2), Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), syphilis and HIV. Univariate and multivariate logistic regression were used to evaluate factors associated with MG. Results MG was detected in 7.2% (49/678) of the patients (men, 7.4%; women, 6.9%). The MG positivity rate was 14.2% among symptomatic patients, and 5.6% for asymptomatic patients, respectively. Only 36.7% (18/49) Mg positive patients were symptomatic. Among the MG-infected patients, 10.2% were co-infected with CT, 6.1% with NG, 8.2% with HSV-2, 4.1% with syphilis and 22.4% with GW. Presentation with clinical symptoms was significantly associated with MG infection [OR = 2.52 (2.03–3.13)]. In our analysis, MG was not associated with other STIs. Conclusions MG is a relatively common infection among individuals attending an STI clinic in Guangdong Province. Routine testing of symptomatic patients may be necessary, and more epidemiological studies are needed to provide evidence for future testing guidelines.

Functional and structural disturbances in the orbitofrontal–striatal–thalamic circuitry are thought to be associated with mental symptoms and neurocognitive impairments in schizophrenia. This study tested whether synapse-associated protein 97 (SAP97), a reasonable candidate gene for schizophrenia, is related to orbitofrontal–striatal–thalamic connection changes in first-episode schizophrenia (FES) patients and the clinical performance of schizophrenic patients by affecting this integrity. Fifty-two FES patients and 52 matched healthy controls were recruited. All subjects underwent genotyping via the improved multiplex ligation detection reaction technique and scanning with magnetic resonance imaging (MRI) to provide orbitofrontal–striatal–thalamic functional and structural imaging data. A two-way analysis of covariance model was employed to examine abnormal brain connectivities, and Spearman correlations were applied to estimate the relationships between brain connectivity and clinical manifestations. In the FES group, those with the SAP97 rs3915512 TT genotype showed lower structural and functional connectivity than A allele carriers between the orbitofrontal gyrus and striatum/thalamus. In the FES group, negative correlations were found between resting-state functional connectivity (RSFC) in the orbitofrontal gyrus and thalamus, and positive symptoms between structural connections in the orbitofrontal gyrus and striatum and cognitive functions, and positive correlations were suggested between RSFC in the orbitofrontal gyrus and thalamus and negative symptoms. Our findings suggested that the SAP97 rs3915512 polymorphism may be involved in mental symptoms and cognitive dysfunction in FES patients by influencing structural and functional connectivity of the orbitofrontal–striatal and orbitofrontal–thalamic regions.

Radiation-induced brain injury is a major adverse event in head and neck tumor treatment, influencing the quality of life for the more than 50% of patients who undergo radiation therapy and experience long-term survival. However, no effective treatments are available for these patients, and preventative drugs and effective drug-delivery methods must be developed. Based on our results, miR-122-5p was upregulated in the mouse radiation-induced brain injury (RBI) model and patients with nasopharyngeal carcinoma (NPC) who received radiation therapy. Intranasal administration of a single antagomiR-122-5p dose before irradiation effectively alleviated radiation-induced cognitive impairment, neuronal injury, and neuroinflammation in the mouse RBI model. Results further indicated that miR-122-5p inhibition in microglia reduced the levels of proinflammatory cytokines and enhanced the phagocytic function to protect against radiation-induced neuronal injury in cell models. Further, we profiled transcriptome data and verified that Tensin 1 (TNS1) may be the target of miR-122-5p in RBI. In summary, our results reveal a distinct role for miR-122-5p in regulating neuroinflammation in RBI, indicating that a non-invasive strategy for intranasal miR-122-5p administration may be an attractive therapeutic target in RBI, providing new insights for clinical trials. Further systematic safety assessment, optimization of drug administration, and clarity of mechanism will accelerate the process into clinical practice.

Nuclear casein kinase and cyclin-dependent kinase substrate 1 (nucks1) are considered a potential susceptibility gene for certain neurological diseases, such as Parkinson’s disease (PD). In our study, we genotyped three single nucleotide polymorphisms (SNPs) (rs4951261, rs823114 and rs951366) of the nucks1 gene in 774 schizophrenic patients and 819 healthy controls using the improved multiplex ligation detection reaction (imLDR) technique. Furthermore, we also studied the relationship between the above SNPs and the clinical psychiatric symptoms and neurocognitive function of the patients. Genotype distributions and allele frequencies of these SNPs showed no significant differences and were found between patients and healthy controls. However, in an analysis of the positive symptom score of rs823114 among male patients, we found that the score of the A/A genotype was lower than that of the G/A+G/G genotypes (P = 0.001, P(corr) = 0.003]. Additionally, we also found that among the female patients, G allele carriers with rs823114 had lower semantic fluency scores than subjects with the A/A genotype (P = 0.010, P(corr) = 0.030]. Our data show for the first time that rs823114 polymorphism of nucks1 may affect positive symptoms and neurocognitive function in patients with schizophrenia in parts of southern China.

High blood glucose has been noted in case reports of acute thallium poisoning, however, effects of low-level exposure of thallium on risk of gestational diabetes mellitus (GDM) has not been explored yet.We aimed to explore the association of serum thallium concentration (STC) in early pregnancy and risk of GDM.Data of 3013 women from the Ma'anshan birth cohort study (MABC), China was used. STC was measured by inductively coupled plasma mass spectrometry (ICP-MS). Multivariate logistic regression was performed to the association of STC and risk of GDM. Stratified analysis was carried out according to maternal age and pre-pregnancy BMI.We documented 383 incident GDM (12.7%). The STC ranged from 0.011 to 0.232 μg/L with a median of 0.062 μg/L. Women with advanced age and higher pre-pregnancy BMI tended to have higher level of STC. Individuals in GDM-group have higher level of STC than that in non-GDM group (P = 0.007). Maternal STC in early pregnancy was associated with risk of GDM, but the association attenuated to non-significance after adjusted for pre-pregnancy BMI. In the advanced age (30 years) group, STC was significantly associated with risk of GDM in a dose-response manner (P for trend0.05). Compared with the Quintile 1, the odds ratios (ORs) (95% confidence interval, CI) of Quintile 2, Quintile 3, Quintile 4, and Quintile 5 were 1.48 (0.62-3.53), 2.70 (1.21-6.03), 2.85 (1.29-6.31), 2.30 (1.05-5.05) in the most adjusted model (including pre-pregnancy BMI).Our study was the first study to demonstrate an association of maternal STC in early pregnancy and risk of GDM, and the association was partly mediated by pre-pregnancy BMI. This association exhibited as an age-dependent manner. Our study highlights even very low-level of thallium exposure could already pose a threat to human's health.

Cobalt is an essential trace element and has been suggested to be involved in oxidative stress and inflammatory responses. However, researches have paid little attention to the association between serum cobalt levels during pregnancy and the risk of preterm birth (PTB

Background Low birth weight infants (LBW) are at risk of chronic diseases in later life due to the disorder of energy metabolism during pregnancy. Osteocalcin (OC) has been identified as a hormone that regulate energy metabolism. However, few studies have researched on the associations between maternal serum OC levels and low birth weight infants. Objections To examine the associations between maternal serum OC concentrations and LBW. Methods This was a nested case-control study involving a total of 230 pregnant women delivering LBW and 382 control pregnant women (matched for infant gender, gestational age at blood draw, region of Maternity and Child Healthcare Hospital and maternal age in 1: (1–2) ratio). One serum sample was collected from each pregnant woman at 5–35 weeks' gestation. Pregnant women were divided into 3 groups (1st, 2nd and 3rd trimester group). There were 60 and 142 and 28 pregnant women delivering LBW in the first, second and third trimester, respectively. Similarly, there were 101 and 233 and 48 controls in the first, second and third trimester, respectively. Maternal serum OC and 25(OH)D concentrations were categorized into low and high levels, the low level used as reference in analyses. Binary logistic regression model was used to compute odd radio (ORs) for LBW according to levels of maternal serum OC and 25(OH)D. Results Compared with the subjects in low level in first trimester, LBW was two times as likely to occur among pregnancy women with high serum OC concentrations (OR = 2.04, 95%CI:1.05–3.96). After adjusted for confounding factors, a significant positive relationship still existed (adjusted ORs = 2.29, 95%CI: 1.11–4.72). In second trimester, women in high level of serum OC had nearly 1.6 times the risk of delivering LBW infants as those in the low level (OR = 1.55, 95%CI: 1.01–2.37). After adjusted for confounding factors, the ORs increased (ORs = 1.59, 95%CI:1.03–2.45). No significant associations were found between maternal serum OC levels and LBW in third trimester. In addition, there were no associations between maternal 25(OH)D concentrations and LBW during pregnancy. Conclusion High maternal serum OC levels in the first or the second trimester during pregnancy may be associated with the risk of LBW.

Objective: To investigate the effects of microRNA-137 (MIR137) polymorphisms (rs1198588 and rs2660304) on the risk of schizophrenia in a Han Chinese population.Methods: Schizophrenia was diagnosed according to the DSM-5. Clinical symptoms and cognitive functions were assessed with the Positive and Negative Symptom Scale (PANSS) and Brief Assessment of Cognition in Schizophrenia (BACS), respectively. The polymorphisms were genotyped by improved multiplex ligation detection reaction (iMLDR) technology in 1,116 patients with schizophrenia and 1,039 healthy controls.Results: Significant associations were found between schizophrenia and MIR137 in the distributions of genotypes (p = 0.037 for rs1198588; p = 0.037 for rs2660304, FDR corrected) and alleles (p = 0.043 for rs1198588; p = 0.043 for rs2660304, FDR corrected) of two SNPs. When the population was stratified by sex, we found female-specific associations between MIR137 and schizophrenia in terms of genotype and allele distributions of rs1198588 (χ2 = 4.41, p = 0.036 and χ2 = 4.86, p = 0.029, respectively, FDR corrected) and rs2660304 (χ2 = 4.74, p=0.036 and χ2 = 4.80, p = 0.029, respectively, FDR corrected). Analysis of the MIR137 haplotype rs1198588-rs2660304 showed a significant association with schizophrenia in haplotype T-T [χ2 = 4.60, p = 0.032, OR = 1.32, 95% CI (1.02–1.70)]. Then, significant female-specific associations were found with the haplotypes T-T and G-A [χ2 = 4.92, p = 0.027, OR = 1.62, 95% CI (1.05–2.50); χ2 = 4.42, p = 0.035, OR = 0.62, 95% CI (0.39–0.97), respectively]. When the TT genotype of rs1198588 was compared to the GT+GG genotype, a clinical characteristics analysis also showed a female-specific association in category instances (t = 2.76, p = 0.042, FDR corrected).Conclusion: The polymorphisms within the MIR137 gene are associated with susceptibility to schizophrenia, and a female-specific association of MIR137 with schizophrenia was reported in a Han Chinese population.

Our previous study suggested that the synapse-associated protein 97 (SAP97) gene rs3915512 polymorphism may influence neurocognition in schizophrenia patients. Neuroimaging studies have shown a possible association between cognitive function and brain activity/connectivity. Considering the poor understanding of whether the disease state and SAP97 rs3915512 polymorphism have interactive effects on brain activity/connectivity, 52 first-episode schizophrenia (FES) patients and 52 healthy controls were genotyped using blood DNA samples and underwent magnetic resonance imaging scanning. A two-way ANCOVA model was performed with rs3915512 genotypes and disease state as the between-subject factors. A significant disease × SAP97 interactive effect was found for the amplitude of low-frequency fluctuation (ALFF) in the right supplementary motor area, left rolandic opercularis area (ROC-L), and bilateral middle occipital gyrus (MOG). In addition, among auditory/visual-related brain areas, a significant interactive effect was found for resting-state functional connectivity (RSFC) between the MOG-L and bilateral superior temporal gyrus (STG) in the STG-L with ROC-R, right cuneus (Cu-R), left fusiform (Fu-L), and left lingual gyrus (LG-L). Positive correlations were found between ALFF in the ROC-L and motor speed scores, between RSFC in the STG-L and LG-L and between Brief Assessment of Cognition in Schizophrenia verbal memory scores in FES. The SAP97 rs3915512 polymorphism may affect neurocognitive function in patients with schizophrenia by changing the brain activity and connectivity of auditory/visual-related brain areas.

Thallium, a highly toxic heavy metal and priority pollutant, has been widely reported to cause neurodevelopmental toxicity in animals. However, accessible epidemiological studies concerning the neurodevelopmental toxicity of early-life thallium exposure in humans are limited. In a prospective birth cohort including 2164 mother-child pairs, we explored the effect of prenatal serum thallium exposure on cognitive development among preschool-aged children born in Ma'anshan, Anhui, China. Serum thallium concentrations were measured in the first trimester, second trimester, third trimester, and cord blood by inductively coupled plasma mass spectrometry (ICP-MS). Child cognitive development was appraised by the Chinese version of the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition (WPPSI-IV) at 4.5 years old. Multiple informants generalized estimating equations (GEEs) were fit to jointly estimate the association between the four repeated measurements of thallium concentrations and the preschool-aged children's cognitive test scores. After adjusting for potential confounders, the visual spatial index (VSI) was 1.45 points lower in the highest tertile of serum thallium during the first trimester than in the lowest tertile (p for trend = 0.04). Moreover, children in the highest tertile of serum thallium during the third trimester had a significantly lower full-scale intelligence quotient (FSIQ) (β = −1.51, 95% CI: 2.68, −0.35), VSI (β = −1.79, 95% CI: 3.16, −0.42), fluid reasoning index (FRI) (β = −1.41, 95% CI: 2.73, −0.10), and processing speed index (PSI) (β = −1.47, 95% CI: 2.71, −0.24) scores than the children in the lowest tertile. When performing stratified analysis by child sex, the associations of first- and third-trimester thallium concentrations with cognitive test scores were more prominent in boys than in girls. Our findings revealed that maternal serum thallium exposure during the first and third trimesters, but not other periods, had detrimental effects on preschoolers' cognitive development, and these effects showed sex differences.

Prevalence of co-infecting sexually transmitted infections (STIs) among patients newly diagnosed with anogenital warts is under-reported. Our objective is to determine the prevalence of six common STIs, Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Mycoplasma genitalium (MG), genital herpes (herpes simplex virus type 2 [HSV-2]), HIV, and syphilis for patients visiting a sexual health clinic in Guangzhou, China. Demographics, sexual health, and medical histories were collected at patient intake. Patients diagnosed with anogenital warts (N = 200) were invited to participate. We collected urine samples, and urethral, cervical, and rectal swabs to test for CT, NG, and MG, and blood samples for serological detection of HSV-2, syphilis, and HIV. Overall 49 (24.5%) had a co-infection (22.2% of men and 27.7% of women). All six STIs were observed among men: CT (6.8%), NG (3.4%), MG (5.1%), HIV (4.3%), HSV-2 (4.3%), and syphilis (1.7%). Women had fewer STIs, but at higher rates: CT (13.3%), MG (6.0%), and HSV-2 (8.4%). Individual men had up to two co-infections, while women had no more than one co-infection. Chlamydia was the most common STI. Patients aged 18–25 years (35.4%) had the highest prevalence. Although opportunistic screening is often applied for high-risk groups, expansion to patients with anogenital warts in all health-care settings would improve detection of problematic asymptomatic co-infections, thereby increasing China’s capacity to contribute toward global surveillance systems.

Background and methods Based on our previous discovery that SAP97 rs3915512 polymorphism significantly affects the cognitive function of schizophrenia, we further genotyped the other 12 single-nucleotide polymorphisms (SNPs) capturing the known common haplotype variations of this gene in a sample including 1014 patients with schizophrenia and 1078 matched controls. Results There were no significant differences in the distribution of genotypes and alleles of the 12 SNPs of SAP97 between the patients and the controls (all P > 0.05). But, in the evaluation of the phenotypic effects of these SNPs on the patients' clinical symptoms and cognitive functions. While patients with minor allele in the rs9843659 polymorphism had higher N5 (difficulty in abstract thinking) scores than that with the main genotype (P = 0.002, Pcor = 0.014), the patients with minor allele in the rs6805920, rs4916461 and rs7638423 had lower verbal memory scores (P = 0.003, 0.003, 0.001, Pcor = 0.021, 0.021, 0.007, respectively) and the P values of these SNPs were still significant after the Bonferroni correction. Conclusion Our data are further to indicate that the SAP97 gene polymorphisms may affect neurocognitive function especially verbal memory and the first to suggest that the SAP97 rs9843659 polymorphism may influence abstract thinking of schizophrenic patients in the southern Han Chinese population.

Background: The factors that cause recurrent wheezing in children are complex, and premature delivery may be one of these factors. Little is known about early wheezing in preterm infants.Methods: Data were sourced from 1616 children born between 2007 and 2013 from 8 hospitals in Guangxi, China. All children were followed up by telephone or questionnaire through the sixth year of life. Children were grouped by gestational age (GA): Group A, GA ≤ 32 weeks; Group B, 32 weeks < GA < 37 weeks; and Group C, 37 weeks ≤ GA < 42 weeks.Results: The incidences and risk factors for early wheezing in preterm infants were analysed. The incidences of early wheezing were as follows: Group A > Group B > Group C. The incidence of persistent early wheezing in Group A or Group B was significantly higher than that in Group C, respectively. SGA (95% CI: 1.097 to 7.519) was a risk factor for early wheezing in group A. Male sex (95% CI: 1.595 to 4.501) and family history of allergies (95% CI: 1.207 to 3.352) were risk factors for early wheezing in group B.Conclusions: 1. New-borns with younger GAs had a higher risk of early wheezing. 2. The incidence of persistent early wheezing for preterm infants (GA ≤ 32 weeks and 32 weeks < GA < 37 weeks) was higher than that for full-term infants (37 weeks ≤ GA < 42 weeks). 3. SGA was a risk factor for early wheezing in preterm infants with a GA ≤ 32 weeks. 4. Male sex, personal history of allergies and family history of allergies were all possible factors affecting early wheezing in preterm infants with a GA > 32 weeks but < 37 weeks and full-term infants. Among them, male sex and family history of allergies were risk factors for early wheezing. 5. Mode of delivery, passive smoking, breastfeeding and invasive mechanical ventilation were not possible risk factors for early wheezing in infants of different GAs.

Progressive functional deterioration and loss of neurons underlies neurological diseases and constitutes an important cause of disability and death worldwide. The causes of various types of neurological diseases often share several critical nerve-related cellular mechanisms and pathological features, particularly the neuroinflammatory response in the nervous system. A rapidly growing body of evidence indicates that various microRNAs play pivotal roles in these processes in neurological diseases and might be viable therapeutic targets. Among these microRNAs, microRNA-146a (miR-146a) stands out due to the rapid increase in recent literature on its mechanistic involvement in neurological diseases. In this review, we summarize and highlight the critical role of miR-146a in neurological diseases. MiR-146a polymorphisms are associated with the risk of neurological disease. Alterations in miR-146a expression levels are crucial events in the pathogenesis of numerous neurological diseases that are spatially and temporally diverse. Additionally, the target genes of miR-146a are involved in the regulation of pathophysiological processes in neurological diseases, particularly the neuroinflammatory response. In summary, miR-146a mainly plays a critical role in neuroinflammation during the progression of neurological diseases and might be a prospective biomarker and therapeutic target. Understanding the mechanisms by which miR-146a affects the neuroinflammatory response in different neurological injuries, different cell types, and even different stages of certain neurological diseases will pave the way for its use as a therapeutic target in neurodegenerative diseases.

Background The potential maternal and neonatal thyrotoxicity associated with exposure to arsenic during pregnancy is very limited and unclear. Objectives This study aimed to examine the associations between arsenic exposure levels in maternal and cord serum and maternal and neonatal thyroid hormone parameters in a prospective birth cohort study. Methods The study including 2089 mother-neonate pairs was based upon Ma’an Shan birth cohort study in China. The exposure variables including maternal serum arsenic levels in the first, second and third trimester and average arsenic exposure level during pregnancy and cord serum arsenic level. Maternal serum TSH and FT4 levels in the first, second and third trimester and cord serum TSH and FT4 levels were determined using the electrochemiluminescence immunoassay with Cobas Elecsys 411. Linear mixed models were used to examine associations between arsenic exposure variables during pregnancy and maternal thyroid hormone parameters, and multiple linear regression analyses were used to examine associations between arsenic exposure during pregnancy and neonatal thyroid hormone parameters. Bayesian kernal machine regression (BKMR) analyses based on a kernel function were also used to examine the effects of exposure to metal mixtures (arsenic, mercury, cadmium and selenium). Results The geometric means of arsenic exposure levels across 3 trimesters were 1.74 μg/L, 1.81 μg/L and 1.99 μg/L, respectively, and 1.90 μg/L in cord serum; the geometric means of maternal FT4 levels across 3 trimesters were 16.91 pmol/L, 11.91 pmol/L and 13.16 pmol/L, respectively, and 16.10 pmol/L in cord serum; the geometric means of maternal TSH levels across 3 trimesters were 1.27 μIU/mL, 2.32 μIU/mL and 2.08 μIU/mL, respectively, and 8.47 μIU/mL in cord serum. Maternal serum arsenic levels in the first, seond, third trimester and average arsenic exposure level during pregnancy were all not associated with maternal thyroid hormone parameters after adjustment for all the covariates, the adjusted β (95% CI) were −0.002 (−0.10 to 0.09), 0.05 (−0.05 to 0.16), −0.09 (−0.17 to 0.003) and −0.05 (−0.22 to 0.11) for maternal FT4, respectively; and −0.005 (−0.04 to 0.03), −0.003 (−0.04 to 0.03), −0.004 (−0.03 to 0.02) and −0.01 (−0.06 to 0.04) for maternal lnTSH, respectively. Maternal serum arsenic levels in the first, second trimester and average arsenic exposure level during pregnancy were all inversely associated with neonatal FT4 level after adjustment for all the confounders, the adjusted β (95% CI) were −0.19 (−0.31 to −0.07), −0.14 (−0.26 to −0.01), −0.22 (−0.42 to −0.02), respectively; and cord serum arsenic level was positively related with neonatal TSH level, the adjusted β (95% CI) were 0.04 (0.001 to 0.08). The adverse joint toxic effect of the four metals in maternal serum in the first trimester and in cord serum on neonatal thyroid hormone parameters were also found. Conclusions In this study, exposure to low levels of arsenic during pregnancy could directly affect neonatal thyroid hormone parameters without being mediated by maternal effect of exposure, and maternal serum arsenic levels in the first, second trimester and average arsenic exposure level during pregnancy and cord serum arsenic level may be risk factors affecting neonatal thyroid hormones. These findings indicate that neonates are more sensitive to the thyrotoxicity of arsenic exposure even at low levels. In addition, the adverse joint toxic effect of metal mixtures is also worthy of attention.

Background Antimicrobial resistance in M. genitalium is a growing clinical problem. We investigated the mutations associated with macrolide and fluoroquinolone resistance, two commonly used medical regimens for treatment in China. Our aim is to analyze the prevalence and diversity of mutations among M. genitalium-positive clinical specimens in Guangzhou, south China. Methods A total of 154 stored M. genitalium positive specimens from men and women attending a STI clinic were tested for macrolide and fluoroquinolone mutations. M. genitalium was detected via TaqMan MGB real-time PCR. Mutations associated with macrolide resistance were detected using primers targeting region V of the 23S rRNA gene. Fluoroquinolone resistant mutations were screened via primers targeting topoisomerase IV (parC) and DNA gyrase (gyrA). Results 98.7% (152/154), 95.5% (147/154) and 90.3% (139/154) of M. genitalium positive samples produced sufficient amplicon for detecting resistance mutations in 23S rRNA, gyrA and parC genes, respectively. 66.4% (101/152), 0.7% (1/147) and 77.7% (108/139) samples manifested mutations in 23S rRNA, gyrA and parC genes, respectively. A2072G (59/101, 58.4%) and S83I (79/108, 73.1%) were highly predominating in 23S rRNA and parC genes, respectively. Two samples had amino acid substitutions in gyrA (M95I and A96T, respectively). Two samples had two amino acid substitutions in parC (S83I + D87Y). 48.6% (67/138) of samples harbored both macrolide and fluoroquinolone resistance-associated mutations. The most common combination of mutations was A2072G (23S rRNA) and S83I (parC) (40/67, 59.7%). One sample had three amino acid changes in 23S rRNA, gyrA and parC genes (A2072G + A96T + S83I). Conclusions The high antimicrobial resistance rate of M. genitalium in Guangzhou is a very worrying problem and suggests that antimicrobial resistance testing and the development of new antibiotic regimens are crucially needed.

Objective To investigate the relationship between SAP97 genetic polymorphisms and sporadic Parkinson's disease (PD) in Han Chinese population with the expectation of offering genetic data for the early prevention and treatment of the disease. Methods In this study, we genotyped single-nucleotide polymorphisms (SNPs) (rs3915512 and rs9843659) in theSAP97 gene in 317 patients with PD and 317 healthy-matched controls in a Han Chinese population through the improved multiplex ligation detection reaction (imLDR) technique. Then, we analyzed the association of each SNP, alone or in combination, with risk or age of onset of PD. Results The SAP97 rs3915512 and rs9843659 polymorphisms were not associated with the risk of PD. However, the minor allele of the rs3915512 and rs9843659 were significantly more common in PD patients with an early age of onset. Additionally, significant differences in the distribution of the onset age of the PD among different genotypes of the rs9843659 polymorphism. The CA haplotype was significantly related to early onset PD. Conclusions Our data are the first to suggest that the SAP97 SNPs rs3915512 and rs9843659 and the CA haplotype may be significantly associated with early onset PD in China.

The relationship between prenatal arsenic exposure at low levels and poor development in children, especially in regard to neurodevelopment, has aroused several concerns, but the conclusions have been inconsistent. It still remains unclear whether such adverse effect is associated with a specific profile of the developing brain in early life. To investigate the association between arsenic exposure in utero and children’s development and behaviour, we performed a large prospective birth cohort study including 2315 mother-infant pairs in Anhui Province, China. The Ages and Stages Questionnaire of China (ASQ-C) was used to assess the status of children’s development and behaviour at 6 months postpartum, and the levels of arsenic were determined in umbilical cord serum samples. Odds ratios for suspected developmental delay (SDD) in each domain of the ASQ-C clusters were estimated using logistic regression models. Compared with low arsenic levels group, medium and high arsenic levels were significantly associated with the increased risks of SDD in the personal-social domain among infants aged 6 months after adjustment for all potential confounders (OR = 1.33, 95% CI (1.01, 1.75) and OR = 1.47, 95% CI (1.08, 2.00), respectively). Sex stratification analysis demonstrated that this association was stronger in females. The sensitivity analyses also showed that high cord serum arsenic levels were associated with a 1.80-fold (95% CIs (1.12, 2.90)) higher risk of a more severe developmental delay in the personal-social domain among six-month-old females. Our results suggest that low-level arsenic exposure in utero could have an adverse domain-specific effect on children’s development at 6 months of age, particularly among females. Further studies are warranted to support the findings and explore the mechanism of these domain-and sex-specific associations. Keywords: Arsenic, Umbilical cord serum, Development, Prenatal exposure, Infants, China

Autism spectrum disorder (ASD) and dyslexia are both neurodevelopmental disorders with high prevalence in children. Both disorders have strong genetic basis, and share similar social communication deficits co-occurring with impairments of reading or language. However, whether these two disorders share common genetic risks remain elusive. DOCK4 (dedicator for cytokinesis 4), a guanine nucleotide exchange factor (GEF) for the small GTPase Rac1, is one of few genes that are associated with both ASD and dyslexia. Dock4 is important for neuronal development and social behaviors. Two DOCK4 variations, Exon27-52 deletion (protein product: Dock4-945VS) and a missense mutation at rs2074130 (protein product: Dock4-R853H), are associated with dyslexia and/or ASD with reading difficulties. The present study explores the molecular and cellular functions of these two DOCK4 variants on neuronal development, by comparing them with the wild-type Dock4 protein. Notably, it is revealed that both mutants of Dock4 showed decreased ability to activate not only Rac1, but also another small GTPase Rap1. Consistently, both mutants were dysfunctional for regulation of cell morphology and cytoskeleton. Using Neuro-2a cells and hippocampus neurons as models, we found that both mutants had compromised function in promoting neurite outgrowth and dendritic spine formation. Electrophysiological recordings further showed that R853H partially lost the ability to promote excitatory synaptic transmission, whereas 945VS totally lost the ability. Together, we identified R853 as a previously uncharacterized site for the regulation of the integrity of Dock4 function, and provides insights in understanding the common molecular pathophysiology of ASD and dyslexia.

The aim of this study was to explore the impact of prenatal Al and Mg on placental oxidative stress and inflammatory mRNA expression. A total of 2519 pregnant women from the China Ma'anshan birth cohort participated in this study. Al and Mg levels were measured by inductively coupled plasma mass spectrometry (ICP-MS). Placental stress and inflammatory mRNA expression were assessed by RT-PCR. The median Al levels in the first and second trimesters of pregnancy and in cord blood were higher than the corresponding median Mg levels. Predictors of lower Al and Mg levels included Han ethnicity and high education according to a mixed linear model. Multiple linear regression analysis revealed that Al and Al/Mg levels had a positive association with inflammatory mRNA expression and placental oxidative stress in the second trimester of pregnancy. A negative association existed between Al and Al/Mg levels and inflammatory mRNA expression and placenta oxidative stress in the cord blood, with the exception of IL-1β expression. In conclusion, prenatal Al and Mg status was associated with placental oxidative stress and inflammatory mRNA expression. More preclinical studies are needed to confirm the relevant mechanism.

Gestational diabetes mellitus (GDM) is a common obstetric complication with adverse effects on both mothers and their children. Previous studies revealed the link between Arsenic (As) exposure and incidence of diabetes mellitus (DM), but the data on the association between maternal As exposure and GDM is scarce. We examined this association among a population-based birth cohort. As concentrations were determined at multiple time points during pregnancy by ICP-MS. The association between As levels and GDM prevalence was examined using logistic regression model after adjustment for confounders. A total of 419 (12.85%) women were diagnosed with GDM. The incidences of GDM gradually increased with increasing quartiles of As levels with significant trend. As levels were associated with the GDM (95%CI: 1.29-2.43) at only the 4th quartile in the first trimester. After adjustment for maternal age, prepregnancy body mass index (BMI), monthly income, gestational age and parity, the association remains significant (95%CI: 1.22-2.38). Stratified analyses showed the associations were largely limited to normal maternal age (95%CI: 1.19-3.04) and normal weight women (95%CI: 1.18-2.66). Our study showed an association between As and GDM in a birth cohort and explored first trimester may be the critical period for As associated GDM. This association was universal in the general pregnant population of normal age and of normal weight.

Helicobacter pylori (H. pylori) infection can interfere with the absorption of most elements, and the variations of some element levels are related to the incidence of gastric cancer. However, there have been conflicting results concerning the influence of H. pylori infection on serum element levels. The present study aimed to compare the serum element concentrations of H. pylori-infected local residents with uninfected residents from Lujiang County with high gastric cancer risk in Eastern China. We used data and serum samples from the H. pylori screening-survey program which was a cross-sectional study. We took 155 samples randomly from the screening survey, identified 74 H. pylori-positive residents and 81 H. pylori-negative residents by a serological test. The serum concentrations of 15 elements (calcium, magnesium, iron, zinc, selenium, copper, molybdenum, chromium, cobalt, nickel, lead, cadmium, mercury, arsenic, and aluminum) were determined using inductively coupled plasma mass spectrometry. Serum cobalt was found at higher levels in the H. pylori-infected residents than the H. pylori-uninfected residents (0.246 vs 0.205 μg/L, P = 0.022), but no statistically significant differences in the serum levels of other elements were found. This is the first study to report the serum concentrations of 15 elements and their relationships with the infection status of H. pylori among local residents from Lujiang County with high gastric cancer risk. Although the International Agency for Research on Cancer has classified cobalt and other soluble cobalt salts as possibly carcinogenic to human beings, our results may provide a clue to the relationships between cobalt, H. pylori, and gastric cancer.

Cobalt (Co) is an essential trace element and has been suggested to be involved in blood pressure regulation, but few studies have focused on serum Co status during pregnancy and the risks of pregnancy-induced hypertension syndrome (PIH). The aim of this study was to prospectively assess the association between serum Co levels during pregnancy and the risks of PIH, and to explore how the maternal Co status contributes to the incidence of PIH. 3260 non-hypertensive women before pregnancy with singleton births in Ma'anShan birth cohort study (MABC) were recruited with the assessment of maternal Co concentrations, additionally, the levels of 7 inflammatory factors and 3 stress factors in placentas were also determined. Relative risks (RRs) [95% confidence intervals (CIs)] for the risks of PIH were assessed and the relationships between 10 factors and maternal Co status during pregnancy were evaluated as well. A total of 194 (5.95%) women were diagnosed with PIH. The concentrations of Co varied from the first trimester to the second trimester, and maternal serum Co concentrations during pregnancy were negatively associated with the incidence of PIH in a linear fashion. There was a clear trend in RRs according to decreasing exposure to Co levels in the second trimester (RRa=1.80, 95% CI (1.26, 2.56); RRb=1.73, 95% CI (1.21, 2.46) and RRc=1.43, 95% CI (1.02, 2.04) when low Co levels comparing with high Co levels before and after adjustment for confounders; and RRa=1.29, 95% CI (0.88, 1.88); RRb=1.28, 95% CI (0.87, 1.87) and RRc=1.25, 95% CI (0.86, 1.82) when medium Co levels comparing with high Co levels before and after adjustment for confounders). In addition, the trend for the first trimester was nearly identifical to those for the second trimester (RRa=1.35, 95% CI (0.94, 1.93); RRb=1.33, 95% CI (0.93, 1.91); RRc=1.22, 95%CI (0.86, 1.73) when low Co levels comparing with high Co levels before and after adjustment for confounders; and RRa=1.10, 95% CI (0.76, 1.60); RRb=1.13, 95% CI (0.77, 1.64) and RRc=1.12, 95% CI (0.77, 1.63) before and after adjustment for confounders). Interestingly, Co concentrations in the second trimester were also inversely associated with the levels of some inflammatory factors and all three stress factors in placentas. This prospective study suggested that lower maternal serum Co concentration in the second trimester may associate with the incidence of PIH in Chinese population. Additionally, the maternal Co concentrations in the second trimester could reduce inflammatory and oxidative damage to the placenta. Further evidence is needed to support the findings and assess the mechanisms underlying the association.

Thallium (Tl), a ubiquitous environmental toxicant, can cross the placental barrier during pregnancy. However, the effects of prenatal Tl exposure on placental function are currently unclear. Based on the Ma’anshan Birth Cohort study, we examined whether long-term prenatal Tl exposure was associated with placental inflammation. Tl concentrations were quantified in serum samples (n = 7050) from 2515 pregnancy during each trimester, placental inflammatory cytokine mRNA expression was assessed in 2519 placenta tissues. Geometric mean values of serum Tl concentrations were 63.57, 63.63 and 48.71 ng/L for the first, second and third trimesters, respectively. After adjustment for potential confounders, serum Tl concentration was positively associated with CD68 (β: 0.30; 95% CI: 0.05, 0.56) in the first trimester and TNF-α (β: 0.12; 95% CI: 0.01, 0.23), IL-6 (β: 0.15; 95% CI: 0.05, 0.25) and CD68 (β: 0.25; 95% CI: 0.10, 0.39) in the third trimester, however was negatively associated with IL-4 (β: −0.21; 95% CI: −0.41, −0.01) and CD206 (β: −0.23; 95% CI: −0.45, −0.02) in the first trimester. Repeated measures analysis showed that TNF-α, IL-6 and CD68 increased by 0.11 (95% CI: 0.01, 0.21), 0.12 (0.15, 95% CI: 0.05, 0.25), 0.22 (95% CI: 0.10, 0.39), respectively, with each 1ln-transformed Tl increase in total samples. Gender-specific analyses revealed that these associations were largely driven by male offspring. In addition, immunohistochemistry revealed that nuclear NF-κB p65 expression increased in placenta tissue. The results of this prospective cohort study provide longitudinal evidence that prenatal Tl exposure induces a placental inflammatory response in the Chinese population.

Thallium (Tl) is a highly toxic heavy metal that has been suggested to be responsible for oxidative stress and mitochondrial dysfunction. However, few studies have focused on the relationship of prenatal Tl exposure with children's neurobehavioural development. The purpose of our study was to investigate the association between prenatal Tl exposure and attention-deficit/hyperactivity disorder (ADHD) symptoms in 36-month-old children. We used data from 2851 mother-newborn pairs from the Ma'anshan Birth Cohort Study (MABC); serum Tl concentration was assessed in the first, second and third trimesters of pregnancy as well as in the umbilical cord blood. We assessed ADHD symptoms in the children using the Chinese version of the Conners abbreviated symptom questionnaire (C-ASQ). The adjusted odds ratio (OR) for the risk of ADHD symptoms was 2.00 [95% confidence interval (CI): 1.20, 3.32] and 2.08 (95% CI: 1.26, 3.43) for the third (60.25-75.21 ng/L) and fourth quartiles of serum Tl (75.21 ng/L), respectively, in the second trimester of pregnancy, in comparison with the first quartile of serum Tl (50.86 ng/L). The risk of ADHD symptoms was elevated among boys exposed to the fourth quartile of serum Tl in the second trimester of pregnancy (adjusted OR 2.08, 95% CI: 1.13, 3.83). Our results demonstrated that high levels of Tl exposure in the second trimester of pregnancy were related to a higher risk of ADHD symptoms in 36-month-old children, and the association of higher serum Tl exposure in the second trimester with ADHD symptoms was only found in boys.

Objective: Schizophrenia is thought to be a neurodevelopmental disorder. As a key regulator in the development of the central nervous system, transcription factor 4 (TCF4) has been shown to be involved in the pathogenesis of schizophrenia. The aim of our study was to assay the association of TCF4 single nucleotide polymorphisms (SNPs) with schizophrenia and the effect of these SNPs on phenotypic variability in schizophrenia in Southern Chinese Han Population.Methods: Four SNPs (rs9960767, rs2958182, rs4309482, and rs12966547) of TCF4 were genotyped in 1137 schizophrenic patients and 1035 controls in a Southern Chinese Han population using the improved multiplex ligation detection reaction (iMLDR) technique. For patients with schizophrenia, the severity of symptom phenotypes was analyzed by the five-factor model of the Positive and Negative Symptom Scale (PANSS). Cognitive function was assessed using the Brief Assessment of Cognition in Schizophrenia (BACS) scale.Results: The results showed that the genotypes and alleles of the three SNPs (rs2958182, rs4309482, and rs12966547) were not significantly different between the control group and the case group (all P > 0.05). rs9960767 could not be included in the statistics for the extremely low minor allele frequency. However, the genotypes of rs4309482 shown a potential risk in the positive symptoms (P = 0.04) and excitement symptoms (P = 0.04) of the five-factor model of PANSS, but not survived in multiple test correction. The same potential risk was shown in the rs12966547 in positive symptoms of the PANSS (P = 0.03).Conclusion: Our results failed to find the associations of SNPs (rs2958182, rs4309482, and rs12966547) in TCF4 with schizophrenia in Southern Chinese Han Population.

Introduction Schizophrenia is a serious mental illness with a genetic predisposition. Genome‐wide association studies (GWAS) have identified the α‐1C subunit of the L‐type voltage‐gated calcium channel (CACNA1C) gene as a significant risk gene for schizophrenia. However, there are inconsistent conclusions in case–control studies. Methods We performed a comprehensive meta‐analysis of all available samples from existing studies under four different genetic models (recessive model, dominant model, additive model and allele model) to further confirm whether CACNA1C rs1006737 is an authentic risk single nucleotide polymorphism (SNP) for schizophrenia. Results A statistically significant difference under the four models (all p

The aims of our study were to determine whether prenatal mercury levels are associated with the risk of preterm birth (PTB) and whether high maternal serum zinc (Zn) levels alleviate any negative effects of maternal mercury (Hg) exposure regarding PTB.Serum concentrations of Zn and Hg were measured in 3025 pregnant women from the Ma'anshan Birth Cohort. Before the collection of blood samples, they underwent examinations via the completion of questionnaires. The delivery records of the women were obtained from a series of medical records. We divided the study population into tertiles according to the participants' Hg levels: the low-Hg group (the first tertile,0.30 μg/L), the medium-Hg group (the second tertile, 0.30-0.43 μg/L) and the high-Hg group (the third tertile, ≥0.43 μg/L). The associations of Hg exposure with both the risk of PTB and gestational age (weeks) at birth were estimated using a binary logistic regression model and multivariable linear regression analysis, respectively. Afterwards, we conducted a repeated analyses test after the participants were stratified according to their Zn levels, using the 75th percentile division method.Overall, the medians and the interquartile ranges of Hg and Zn in the second trimester were 0.36 (0.27, 0.48) μg/L and 812.34 (731.26, 896.59) μg/L, respectively. Hg levels were associated with PTB [adjusted odds ratio (OR) and 95% confidence interval (95% CI): 1.91 (1.17, 3.12) for the third tertile vs. the first tertile of the serum Hg levels]. In the stratification analysis of the participants in the low-Zn group, the high-Hg group exhibited a significant odds ratio of PTB [adjusted OR (95% CI): 1.87 (1.08, 3.24)], compared to the low-Hg group. However, in the participants from the high-Zn group, the high-Hg group exhibited a non-significant OR of PTB [adjusted OR (95% CI): 2.32 (0.73, 7.42)]. In the multivariate linear regression analysis, gestational age (weeks) at delivery was significantly and inversely associated with the ln-transformed Hg concentrations [adjusted β (95% CI): -0.16 (-0.26, -0.06)]. Similarly, after the stratification analysis in the high-Zn group, there were no significant associations between PTB and the Hg levels [adjusted β (95% CI): -0.12 (-0.33, 0.09)].Prenatal Hg exposure adversely affected PTB, and high Zn levels alleviate this effect, which indicates that a more stringent control of Hg and a sufficient intake of Zn are necessary to help birth outcomes.

Iron is an essential micronutrient while its excessive load has been related to the etiology of diabetes. We used data of 3289 pregnant women from the Ma’anshan birth cohort (MABC) study in China to examine the associations of three iron-related factors (i.e., serum iron (SI) concentration, hemoglobin level, and use of iron supplements) with risk of gestational diabetes mellitus (GDM). Emphatically explore the potential non-linear relationship between SI concentration and risk of GDM. SI concentration was measured in fasting blood using inductively coupled plasma mass spectrometry (ICP-MS). GDM diagnosis was determined by 75 g oral glucose tolerance test at 24~28 weeks. Restricted cubic splines with three knots were used to examine potential non-linear relationship between SI concentration and GDM risk. We observed a U-shape relation between SI concentration in the first trimester and risk of GDM. In the multivariate-adjusted model, compared with the middle level (ln(SI), 7.1–7.7 μg/L), both the lowest level (ln(SI) ≤ 7.1 μg/L) (odds ratio (OR) = 1.35, 95% confidence interval (CI) = 1.04–1.76) and the highest level (ln(SI) > 7.7 μg/L) (OR = 1.63, 95%CI = 1.16–2.28) increased risk of GDM. Associations of hemoglobin level in the first trimester and risk of GDM attenuated to non-significance after adjustment for pre-pregnancy body mass index (BMI) and blood pressure. Pre-pregnancy iron supplement use was associated with an increased risk of GDM (OR = 1.57, 95%CI = 1.06–2.32). In conclusion, the three iron-related factors are all related to GDM risk on some level.

Previous studies have shown the associations between phthalates exposure and psychological behavior problems in children and adolescents, but such associations have not been fully elucidated in university students, especially among Chinese university students. This study aims to examine the association between urinary phthalates metabolites concentration and emotional symptoms in Chinese university students. A school-based cross-sectional survey was carried out among 990 university students aged 17–24 years from two universities in Anhui and Jiangxi provinces of China. Concentration of six phthalate metabolites in urine was determined by high-performance liquid chromatography-tandem mass spectrometry and the emotional symptoms were assessed by the 21-item Depression, Anxiety, and Stress Scale. The detection rate of six phthalate metabolites in urine ranged from 79.6% to 99.7%. The median concentration of six phthalate metabolites ranged from 2.90 to 119.64 ng/mL. The positive rates of depressive symptoms, anxiety symptoms, and stress were 17.4%, 24.8%, and 9.5%, respectively. After adjusting for the confounding variables, mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) was found to be associated with depressive symptoms (β = 8.84, P = 0.017), anxiety symptoms (β = 8.46, P = 0.015), and stress symptoms (β = 9.95, P = 0.012) in males; whereas, monobutyl phthalate (MBP) was found to be associated with depressive symptoms (β = 1.86, P = 0.002), anxiety symptoms (β = 1.81, P = 0.005), and stress symptoms (β = 1.48, P = 0.047) in females. Our study demonstrates that Chinese university students are widely exposed to phthalates; and high- and low-molecular weight phthalates are associated with emotional symptoms in males and females, respectively.

Background: Thallium (Tl) exposure remains a public health problem with potential impacts on humans. Studies have suggested that prenatal exposure to thallium may be associated with fetal growth, but no studies are known have explored its association with early childhood anthropometry. Objective: To investigate the effects of prenatal Tl exposures on early child growth and development aged 0–2 years in a prospective birth cohort study. Methods: 3080 pregnant women and their children participated in the study, which were recruited from a birth cohort in China. Serum samples collected in the first and second trimester of pregnant subjects and umbilical cord blood of infants were analyzed for Tl exposure assessment. Infant length or standing height and weight were obtained from medical records and 2 years planned visits. We used length/height and weight to calculate z-scores for weight-for-age (WAZ), height-for-age (HAZ), weight-for-height (WHZ), and body mass index-for-age (zBMI) based on World Health Organization standards. Linear mixed model was used to investigate the association between serum concentrations of Tl and the children's anthropometric characteristics (WAZ, HAZ, WHZ, and zBMI), and stratification analysis by sex was also examined. Results: The median (P25-P75) of Tl levels in the first trimester, second trimester and umbilical cord serum were 61.7 (50.7–77.0), 60.1 (50.9–74.8) and 38.4 (33.6–43.9) ng/L, respectively. Paired Mann-Whitney tests found Tl concentrations in umbilical cord serum were significantly less than that in maternal serum during the first and second trimesters (all p

The SAP97 gene is located in the schizophrenia susceptibility locus 3q29, and it encodes the synaptic scaffolding protein that interacts with the N-methyl-D-aspartate (NMDA) receptor, which is presumed to be dysregulated in schizophrenia. In this study, we genotyped a single-nucleotide polymorphism (SNP) (rs3915512) in the SAP97 gene in 1114 patients with schizophrenia and 1036 healthy-matched controls in a Han Chinese population through the improved multiplex ligation detection reaction (imLDR) technique. Then, we analyzed the association between this SNP and the patients' clinical symptoms and neurocognitive function. Our results showed that there were no significant differences in the genotype and allele frequencies between the patients and the controls for the rs3915512 polymorphism. However, patients with the rs3915512 polymorphism TT genotype had higher neurocognitive function scores (list learning scores, symbol coding scores, category instances scores and controlled oral word association test scores) than the subjects with the A allele (P = 4.72 × 10−5, 0.027, 0.027, 0.013, respectively). Our data are the first to suggest that the SAP97 rs3915512 polymorphism may affect neurocognitive function in patients with schizophrenia.

The present study intended to investigate efficacy of radiotherapy in the treatment of intermediate and advanced stage lung cancer and the effects on serum vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9). Serum levels of VEGF and MMP-9 of 77 patients with intermediate or advanced lung cancer were detected before and after the treatment. At the same time, 19 healthy people were selected as the control group. Gelatin zymography was applied to measure the activity of serum MMP-9, ELISA was performed to detect the VEGF and MMP-9 levels in the peripheral blood and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to measure the messenger RNA (mRNA) levels of VEGF and MMP-9 in serum. Results indicated that the overall response rate of radiotherapy on intermediate and advanced lung cancer reached 70.1%. Levels of serum VEGF and MMP-9 in the effective treatment group were significantly lower than those before the treatment (P

Our study aimed to assess the distribution of copper (Cu) in umbilical cord serum and estimated the association between umbilical serum Cu status and neonatal birth outcomes in a Chinese population. Through the Ma'anShan Birth Cohort Study, 2689 maternal-singleton pairs with detailed birth records and available serum samples were identified. The tertile levels of ln-transformed Cu were used to define low, medium, and high levels for serum Cu. The median for umbilical cord serum Cu was 298.2 μg/L with a range of 123.1-699.6 μg/L in this study population. Our study found a positive association between the concentration of serum Cu in the umbilical cord and the duration of gestation. Compared with medium Cu levels, we found that infants with low Cu levels had a significant higher risk of preterm birth (OR = 5.06, 95% CI 2.74, 9.34) and early-term birth (OR = 1.36, 95% CI 1.10, 1.69) in the crude model. We also found that infants with high Cu levels had a significant higher risk of late- or post-term birth (OR = 1.47, 95% CI 1.11, 1.95). A significant higher risk of preterm, early-term, and late- or post-term birth still remained, even after adjustment for potential confounding factors. Our findings suggested that both Cu deficiency and Cu overload had an adverse effect on neonatal birth outcomes.

Epidemiological studies indicated that there is an increased risk of respiratory tract cancer among cooks and bakers. The cooking oil fumes are believed to conduct this risk, and many studies have focused on evaluating the mutagenicity and finding the mutagenic components in oil fumes. COFs contains two major classes of compounds. One class consists of polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene, benzo[b]fluoranthene, fluoranthene, and benzo[g,h,i]perylene. BaP is a known immunosuppressant. It can also alter cell cycle progression, induce inflammation, and impair DNA repair and apoptotic processes leading to aberrant cellular functioning. This study investigates the effect of toxicity of cooking oil fumes (COFs) in primary ICR mice' fetal lung type II-like epithelium cells (AEC II). The cells were cultured in different concentrations (0, 12.5, 25, 50, 100, and 200μg/ml) of COFs for different time periods. The results showed that cell viability decreased in a dose- and time- dependent manner, which is accompanied by increased malondialdehyde (MDA) level and decreased superoxide dismutase (SOD) and glutathione (GSH) activities. Moreover, comet assay suggested DNA damage, as well as increased production of DNA adducts induced by PAHs. The present study also shows that COFs may disturb cell cycles even at a very low dose. In summary, the present study indicates that COFs may lead to toxicity in AEC II cells.

Analyzing the concentrations of heavy metals in the sera of umbilical cord blood samples can provide useful information about prenatal exposure to environmental agents. An analytical method based on ICP-MS to simultaneously determine multiple elements in umbilical cord blood samples was developed for assessing the in utero exposure to metallic and metalloid elements. The method only required as little as 100 μL of serum diluted 1:25 for direct analysis. Matrix-matched protocol was used to eliminate mass matrix interference and kinetic energy discrimination mode was used to eliminate the polyatomic ion interference. The assay was completed on average within 4 min with the detection limits ranging from 0.0002 to 44.4 μg/L for all the targeted elements. The detection rates for most of elements were 100 % other than cadmium (Cd), lead (Pb), and mercury (Hg). The testing results of the certified reference materials were ideal. The method is simple and sensitive, so it is suitable for the monitoring of large quantities of samples.

Coronary angiography is the gold standard for the diagnosis of coronary artery disease. Coronary artery Gensini scoring systems measure both the extent and the degree of stenosis of coronary artery and therefore, give clinicians a more accurate, objective, and comprehensive assessment of the severity of coronary artery disease. Using Gensini scoring systems in combination with statistical analysis, we found that five variables, namely, Brachial-ankle pulse wave velocity (PWV), ankle-brachial index (ABI), carotid artery intima-media thickness (IMT), blood sugar, and high density lipoprotein cholesterol (HDL-C), were all significantly different among groups of patients with different Gensini scores. All five variables can be used for early screening and assessment of coronary artery disease as independent prognostic factors for the morbidity and mortality from cardiovascular conditions. With the progression of coronary artery disease, the levels of PWV, IMT, and blood glucose are gradually increasing whereas the levels of ABI and HDL-C are gradually decreasing. These changes can be treated as warning signs and can also be helpful in evaluating the severity of coronary artery diseases. It is highly recommended to perform these five non-invasive tests as early as possible in order to identify high-risk patients at their subclinical stages. This would allow timely intervention and thereby lead to reduced morbidity and mortality from cardiovascular diseases.

Asthma is a complex multigenic disease in which gene–environment interactions play a critical role in disease onset and progression. Transforming growth factor-β1 (TGF-β1) is one of several candidate locus for the pathogenesis of asthma, and is highly polymorphic. To derive a more precise estimation of the relationship between the T869C and C-509T polymorphisms of the TGF-β1 gene and asthma, a meta-analysis of 24 published case–control studies was conducted. 20 studies for C-509T polymorphism and 8 studies for T869C polymorphism were included. The pooled odds ratios were calculated respectively for allele contrasts, additive genetic model, dominant genetic model and recessive genetic model. Subgroup analyses were also performed by ethnicity, age, atopic status and asthma severity for two gene polymorphisms. In regard to T869C polymorphism, significant associations with asthma were observed in recessive (OR 1.23, 95%CI 1.00–1.51 and P = 0.047), additive and allele models. In the subgroup analysis by age, significant risks were also found in the recessive model for adults (OR 1.31, 95%CI 1.02–1.69 and P = 0.032), atopic asthma (OR 1.63, 95%CI 1.07–2.49 and P = 0.023). With respect to C-509T polymorphism, significant associations with asthma were demonstrated in the overall analysis and subgroup analyses in the dominant model for Asian (OR 1.37, 95%CI 1.04–1.81 and P = 0.025), Adults (OR 1.26, 95%CI 1.02–1.56 and P = 0.035), Children (OR 1.19, 95%CI 1.01–1.40 and P = 0.034). Potentially functional TGF-β1 C-509T and T869C polymorphisms may be risk factors for asthma susceptibility.