Expression Quantitative Trait Methylation Analysis Identifies Whole Blood Molecular Footprint in Fetal Alcohol Spectrum Disorder (FASD).

Fetal alcohol spectrum disorder (FASD) encompasses neurodevelopmental disabilities and physical birth defects associated with prenatal alcohol exposure. Previously, we attempted to identify epigenetic biomarkers for FASD by investigating the genome-wide DNA methylation (DNAm) profiles of individuals with FASD compared to healthy controls. In this study, we generated additional gene expression profiles in a subset of our previous FASD cohort, encompassing the most severely affected individuals, to examine the functional integrative effects of altered DNAm status on gene expression. We identified six differentially methylated regions (annotated to the SEC61G, REEP3, ZNF577, HNRNPF, MSC, and SDHAF1 genes) associated with changes in gene expression (p-value < 0.05). To the best of our knowledge, this study is the first to assess whole blood gene expression and DNAm-gene expression associations in FASD. Our results present novel insights into the molecular footprint of FASD in whole blood and opens opportunities for future research into multi-omics biomarkers for the diagnosis of FASD.

Electrical stimulation of the splenic nerve bundle ameliorates dextran sulfate sodium-induced colitis in mice.

BACKGROUND: Vagus nerve stimulation has been suggested to affect immune responses, partly through a neuronal circuit requiring sympathetic innervation of the splenic nerve bundle and norepinephrine (NE) release. Molecular and cellular mechanisms of action remain elusive. Here, we investigated the therapeutic value of this neuromodulation in inflammatory bowel disease (IBD) by applying electrical splenic nerve bundle stimulation (SpNS) in mice with dextran sulfate sodium (DSS)-induced colitis. METHODS: Cuff electrodes were implanted around the splenic nerve bundle in mice, whereupon mice received SpNS or sham stimulation. Stimulation was applied 6 times daily for 12 days during DSS-induced colitis. Colonic and splenic tissues were collected for transcriptional analyses by qPCR and RNA-sequencing (RNA-seq). In addition, murine and human splenocytes were stimulated with lipopolysaccharide (LPS) in the absence or presence of NE. Single-cell RNA-seq data from publicly available data sets were analyzed for expression of ß-adrenergic receptors (ß-ARs). RESULTS: Colitic mice undergoing SpNS displayed reduced colon weight/length ratios and showed improved Disease Activity Index scores with reduced Tumor Necrosis Factor α mRNA expression in the colon compared with sham stimulated mice. Analyses of splenocytes from SpNS mice using RNA-seq demonstrated specific immune metabolism transcriptome profile changes in myeloid cells. Splenocytes showed expression of ß-ARs in myeloid and T cells. Cytokine production was reduced by NE in mouse and human LPS-stimulated splenocytes. CONCLUSIONS: Together, our results demonstrate that SpNS reduces clinical features of colonic inflammation in mice with DSS-induced colitis possibly by inhibiting splenic myeloid cell activation. Our data further support exploration of the clinical use of SpNS for patients with IBD.

Changes of proportion regarding consistent condom use and syphilis infection among low-fee female sex workers aged 35 and above / 中华流行病学杂志

Objective: To investigate the changes of proportion on both consistent condom use and syphilis infection among low-fee female sex workers aged 35 and above (LFSW), in order to provide evidence for targeted intervention strategies. Methods: A total of six cities-Liuzhou city and Pingnan couty of Guigang city of Guangxi Zhuang Autonomous Region, Jinghong city of Xishuangbanna Dai autonomous prefecture and Dali city of Dali Bai autonomous prefecture of Yunnan province, Zhangjiajie city and Jianghua Yao autonomous county of Yongzhou city Hunan province were involved in this study, with 60 eligible participants needed in each city, estimated through a pre-study. The first cross-sectional survey was completed from October 2012 to January 2013. Face-to-face questionnaire interview was carried out to collect information on socio-demography, work-related information and condom use situation. Blood was collected for syphilis testing. The second cross-sectional survey was carried out from June to September, 2015 under the same procedure. Results: A total of 371 and 403 eligible participants were included in the first and second survey, respectively. When comparing the two surveys, we noticed that the average age showed a slight change, from 42.4 years to 43.8 years old (t=3.537, P<0.001) and the average price for every commercial sex exchange increased from 36.8 RMB to 49.5 RMB (t=11.961, P<0.001). In the first survey, 46.9% (174/371) of the participants had more than two years of experience working as LFSW, compared to 61.3% (247/403) in the second survey (χ(2)=16.125, P<0.001). Also, 46.9% (174/371) of the participants consistently used condoms with clients in the past month in the first survey versus 64.3% (259/403) (χ(2)=23.641, P<0.001) in the second one. Rates of syphilis infection were found from 15.9% (59/371) in the first survey reduced to 7.2% (29/403) in the second survey (χ(2)=14.533, P<0.001). Conclusion: Compared with the first survey, the proportion of consistent condoms use showed an increase. Although the proportion of syphilis infection decreased in the second survey, the scope did not meet the criteria on syphilis, set by the government. Targeted intervention strategies on condom promotion and syphilis control should be implemented consistently in this population.