Distinct epigenetic modulation of differentially expressed genes in the adult mouse brain following prenatal exposure to low-dose bisphenol A.

Bisphenol A (BPA) is a common component in the manufacture of daily plastic consumer goods. Recent studies have suggested that prenatal exposure to BPA can increase the susceptibility of offspring to mental illness, although the underlying mechanisms remain unclear. In this study, we performed transcriptomic and epigenomic profiling in the adult mouse brain following prenatal exposure to low-dose BPA. We observed a sex-specific transcriptional dysregulation in the cortex, with more significant differentially expressed genes was observed in adult cortex from male offspring. Moreover, the upregulated genes primarily influenced neuronal functions, while the downregulated genes were significantly associated with energy metabolism pathways. More evidence supporting impaired mitochondrial function included a decreased ATP level and a reduced number of mitochondria in the cortical neuron of the BPA group. We further investigated the higher-order chromatin regulatory patterns of DEGs by incorporating published Hi-C data. Interestingly, we found that upregulated genes exhibited more distal interactions with multiple enhancers, while downregulated genes displayed relatively short-range interactions among adjacent genes. Our data further revealed decreased H3K9me3 signal on the distal enhancers of upregulated genes, whereas increased DNA methylation and H3K27me3 signals on the promoters of downregulated genes. In summary, our study provides compelling evidence for the potential health risks associated with prenatal exposure to BPA, and uncovers sex-specific transcriptional changes with a complex interplay of multiple epigenetic mechanisms.

Neuro-Magnetic Resonance Imaging in Hand, Foot, and Mouth Disease: Finding in 412 Patients and Prognostic Features.

PURPOSE: The aims of this study were to describe the neuroimaging findings in hand, foot, and mouth disease and determine those who may provide prognosis. MATERIAL AND METHODS: Magnetic resonance imaging scans in 412 severe hand, foot, and mouth disease between 2009 and 2014 were retrospectively evaluated. The patients who had the neurological signs were followed for 6 months to 1 year. According to the good or poor prognosis, 2 groups were categorized. The incidence of lesions in different sites between the 2 groups was compared, and multivariate analysis was used to look for risk factors. RESULTS: The major sites of involvement for all patients with percentages were the medulla oblongata (16.1%), spinal anterior nerve roots (12.4%), thoracic segments (11.1%), brain or spinal meninges (8.3%), and so on. There were 347 patients (84.2%) with good prognosis and 65 (15.8%) with poor prognosis in the follow-up. There was a significantly higher rate of lesions involving the cerebral white substance, thalamus, medulla oblongata, pons, midbrain, and spinal cord in the group with poor prognosis. Multivariate analysis showed 2 independent risk factors associated with poor prognosis: lesions located in the medulla oblongata (P < 0.015) and spinal cord (P < 0.001) on magnetic resonance imaging; the latter was the most significant prognostic factor (odds ratio, 29.11; P < 0.001). CONCLUSIONS: We found that the distribution patterns for all patients mainly involved the medulla oblongata, spinal anterior nerve roots, thoracic segments, and brain or spinal meninges. Our findings suggested that patients with lesions located in the medulla oblongata and spinal cord may be closely monitored for early intervention and meticulous management. For children with the symptom of nervous system, they are strongly recommended for magnetic resonance examination.

Updated incidence rates and risk factors of esophageal cancer in Nan'ao Island, a coastal high-risk area in southern China.

Esophageal cancer (EC) is one of the most common cancers in China. The purpose of this study was to investigate the updated incidence rates and risk factors of EC in Nan'ao Island, where the EC incidence rate was chronically the highest in southern China. To calculate the annual incidence rate, data on 338 EC cases from Nan'ao Cancer Registry system diagnosed during 2005-2011 were collected. A case-control study was conducted to explore the EC risk factors. One hundred twenty-five alive EC patients diagnosed during 2005-2011 and 250 controls were enrolled into the case-control study. A pre-test questionnaire on demography, dietary factors, drinking water treatment, and behavioral factors was applied to collect information of all participants. The average EC incidence rates during 2005-2011 were 66.09/105, 94.62/105, 36.83/105 for both genders, males and females, respectively, in Nan'ao Island. The EC incidence rate in males was 2.40- to 4.55-fold higher than that in females in the period from 2006 to 2011 (P < 0.05). Considering the onset age, males tend to be much younger than females and reached peak incidence rate at a younger age (P < 0.05). Drinking water treatment by filter (odds ratio [OR] = 0.28, 95% confidence interval [95% CI] = 0.13-0.58) and fruit consumption (OR = 0.55, 95% CI = 0.32-0.94) reduced the risk for EC. On the contrary, the pickled vegetables consumption (OR = 2.64, 95% CI = 1.46-4.76) and liquor drinking (OR = 2.32, 95% CI = 1.21-4.44) increased the risk for EC. These results may be of importance for future research on EC etiology and prevention strategies.

A review on the hypoglycemic effect, mechanism and application development of natural dietary polysaccharides.

Diabetes mellitus (DM) as one chronic metabolic disease was greatly increased over recent decades. The major agents treating diabetes have noticeable side effects as well as the tolerability problems. The bioactive dietary polysaccharides from abundant natural resources exhibit good hypoglycemic effect with rare adverse effects, which might serve as a candidate to prevent and treat diabetes. However, the correlations between the hypoglycemic mechanism of polysaccharides and their structure were not mentioned in several studies, what's more, most of the current hypoglycemic studies on polysaccharides were based on in vitro and in vivo experiments, and there was a lack of knowledge about the effects in human clinical trials. The aim of this review is to discuss recent literature about the variety of dietary polysaccharides with hypoglycemic activity, as well the mechanism of action and the structure-function relationship are highlighted. Meanwhile, the application of dietary polysaccharides in functional foods and clinical medicine are realized with an in-depth understanding. So as to promote the exploration of dietary polysaccharides in low glycemic healthy foods or clinical medicine to prevent and treat diabetes.

Association of Chemoradiotherapy Regimens and Survival Among Patients With Nasopharyngeal Carcinoma: A Systematic Review and Meta-analysis.

Importance: The role of induction chemotherapy (IC) or adjuvant chemotherapy (AC) in the treatment of locoregionally advanced nasopharyngeal carcinoma (NPC) remains controversial. Objectives: To update meta-analyses on the association of survival outcomes with IC and AC regimens in patients with locoregionally advanced NPC and assess whether the current evidence is conclusive by a trial sequential analysis (TSA) approach. Data Sources: PubMed, Embase, and Web of Science were searched for articles published from inception until June 1, 2019. Study Selection: Randomized clinical trials that assessed the efficacy of radiotherapy with or without chemotherapy among previously untreated patients and patients with nondistant metastatic NPC. Data Extraction and Synthesis: Data were extracted by 2 investigators from each trial independently and synthesized by the 2 investigators. All trial results were combined and analyzed by a fixed- or random-effects model. Main Outcomes and Measures: Overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS). Results: A total of 8036 patients (median age, 46.5 years; 5872 [73.1%] male) from 28 randomized clinical trials were included in the analysis. Pooled analyses revealed that concurrent chemoradiotherapy (CCRT) was significantly associated with improved OS, PFS, DMFS, and LRFS compared with radiotherapy across all subgroups. The TSA confirmed the treatment outcomes of CCRT compared with radiotherapy. The additional IC regimen was associated with an improvement in OS (hazard ratio [HR], 0.84; 95% CI, 0.74-0.95), PFS (HR, 0.73; 95% CI, 0.64-0.84), DMFS (HR, 0.67; 95% CI, 0.59-0.78), and LRFS (HR, 0.74; 95% CI, 0.64-0.85). These findings were consistent in subgroup analyses of multicenter trials with sample sizes greater than 250, years of survival rate of 5 or greater, median follow-up longer than 5 years, or low risk of bias. However, the additional AC regimen was not associated with a survival benefit in OS (HR, 0.98; 95% CI, 0.78-1.23), PFS (HR, 0.86; 95% CI, 0.70-1.07), DMFS (HR, 0.84; 95% CI, 0.64-1.10), or LRFS (HR, 0.80, 95% CI, 0.59-1.09). The TSA provided sound evidence on the additional benefit of IC but not AC. Conclusions and Relevance: These data suggest a significant association of survival outcomes with CCRT in patients with locoregionally advanced NPC. The addition of IC instead of AC could achieve survival benefits. The potential therapeutic gain of AC should be explored in the future.

To predict the radiosensitivity of nasopharyngeal carcinoma using intravoxel incoherent motion MRI at 3.0 T.

PURPOSE: To investigate intravoxel incoherent motion (IVIM) MRI for evaluating the sensitivity of radiotherapy on nasopharyngeal carcinoma (NPC). RESULTS: The reproducibility between intra-observer and inter-observer was relatively good. D (0.72×10-3 mm2/s±0.14 vs. 0.54×10-3 mm2/s±0.23; P < 0.001) and D* (157.92×10-3 mm2/s±15.21 vs. 120.36×10-3 mm2/s±10.22; P < 0.0001) were significantly higher in effective group than poor-effective group, whereas the difference of f (18.79%±2.51 vs. 16.47%±1.51) and ADC (1.21×10-3 mm2/s±0.11 vs. 1.33×10-3 mm2/s±0.23) could not reach statistical significant between the 2 groups (P > 0.05). CONCLUSIONS: IVIM may be potentially useful in assessing the radiosensitivity of NPC. The higher D value combining with higher D* value might indicate the more radiosensitive of NPC, and increased D* might reflect increased blood vessel generation and parenchymal perfusion in NPC. MATERIALS AND METHODS: Sixty consecutive patients (20 female, range, 27-83 years, mean age, 52 years) newly diagnosed NPC in the stage of T3 or T4 were enrolled. Forty-two of them were divided into effective group clinically after a standard radiotherapy according to the RECIST criteria. IVIM with 13 b-values (range, 0-800 s/mm2) and general MRI were performed at 3.0T MR scanner before and after radiotherapy. The parameters of IVIM including perfusion fraction (f), perfusion-related diffusion (D*), pure molecular diffusion (D) and apparent diffusion coefficient (ADC) were calculated. Two radiologists major in MRI diagnose analyzed all images independently and placed regions of interest (ROIs). Intra-class correlation coefficient (ICC) was used to evaluate intra-observer and inter-observer agreement. And Mann-Whitney test was used to assess the differences between the two groups.

Exploration and validation of radiomics signature as an independent prognostic biomarker in stage III-IVb nasopharyngeal carcinoma.

There is no consensus on specific prognostic biomarkers potentially improving survival of nasopharyngeal carcinoma (NPC), especially in advanced-stage disease. The prognostic value of MRI-based radiomics signature is unclear. A total of 970 quantitative features were extracted from the tumor of 100 untreated NPC patients (stage III-IVb) (discovery set: n = 70, validation set: n = 30). We then applied least absolute shrinkage and selection operator (lasso) regression to select features that were most associated with progression-free survival (PFS). Candidate prognostic biomarkers included age, gender, overall stage, hemoglobin, platelet counts and radiomics signature. We developed model 1 (without radiomics signature) and model 2 (with radiomics signature) in the discovery set and then tested in the validation set. Multivariable Cox regression analysis was used to yield hazard ratio (HR) of each potential biomarker. We found the radiomics signature stratified patients in the discovery set into a low or high risk group for PFS (HR = 5.14, p < 0.001) and was successfully validated for patients in the validation set (HR = 7.28, p = 0.015). However, the other risk factors showed no significantly prognostic value (all p-values for HR, > 0.05). Accordingly, pretreatment MRI-based radiomics signature is a non-invasive and cost-effective prognostic biomarker in advanced NPC patients, which would improve decision-support in cancer care.

CT and MRI findings in focal eosinophilic infiltration of the liver.

OBJECTIVES: To investigate the findings of computed tomography (CT) and magnetic resonance imaging (MRI) of focal eosinophilic infiltration (FEI) of the liver. METHODS: A retrospective study including 29 patients with confirmed FEI of the liver was performed. We evaluated the lesions' number, distribution, size, shape, margin, attenuation or signal intensity characteristics, the enhancement pattern, and some special features. Spearman correlation analysis was used to analyze the correlation between the number of lesions and the eosinophil counts in peripheral blood. RESULTS: In all, 108 lesions were detected in 29 cases, including two cases with single lesion and the remaining 27 cases with multiple lesions. The mean size of all lesions was 34 mm (range, from 3 to 61 mm). 95 (88%) lesions were located in subcapsular parenchyma or surrounding the portal vein. Most (66%) subcapsular lesions were wedge shaped and all lesions surrounding portal vein were round shaped. However, the hepatic parenchymal lesions were irregular or round shaped. All lesions showed ill-defined margins. On pre-contrast CT images, the lesions showed slightly low attenuation or iso-attenuating. On T1-weighted and T2-weighted images, the lesions were slightly iso-/hypointense and hyperintense, respectively. A total of 23 (79.3%) cases were gradually enhanced. Branches of portal vein went through the lesions in all cases; 12 had 'stripe sign' and 16 had 'halo ring sign.' Spearman analysis indicated a significant correlation between the number of lesions and the increased eosinophils in peripheral blood (r = 0.627, p = 0.0003). CONCLUSIONS: Special CT and MRI features and increased eosinophils may strongly suggest the diagnosis of FEI of the liver.

Machine Learning Algorithms for Risk Prediction of Severe Hand-Foot-Mouth Disease in Children.

The identification of indicators for severe HFMD is critical for early prevention and control of the disease. With this goal in mind, 185 severe and 345 mild HFMD cases were assessed. Patient demographics, clinical features, MRI findings, and laboratory test results were collected. Gradient boosting tree (GBT) was then used to determine the relative importance (RI) and interaction effects of the variables. Results indicated that elevated white blood cell (WBC) count > 15 × 109/L (RI: 49.47, p < 0.001) was the top predictor of severe HFMD, followed by spinal cord involvement (RI: 26.62, p < 0.001), spinal nerve roots involvement (RI: 10.34, p < 0.001), hyperglycemia (RI: 3.40, p < 0.001), and brain or spinal meninges involvement (RI: 2.45, p = 0.003). Interactions between elevated WBC count and hyperglycemia (H statistic: 0.231, 95% CI: 0-0.262, p = 0.031), between spinal cord involvement and duration of fever ≥3 days (H statistic: 0.291, 95% CI: 0.035-0.326, p = 0.035), and between brainstem involvement and body temperature (H statistic: 0.313, 95% CI: 0-0.273, p = 0.017) were observed. Therefore, GBT is capable to identify the predictors for severe HFMD and their interaction effects, outperforming conventional regression methods.

Downregulation of pigment epithelium-derived factor in condyloma acuminatum.

OBJECTIVES: To investigate pigment epithelium-derived factor (PEDF) mRNA and protein levels in condyloma acuminatum, and their relationship with angiogenesis and keratinocyte proliferation. METHODS: Lesions from male patients with condyloma acuminatum and skin from healthy male (control) subjects were collected. Levels of PEDF protein and its corresponding mRNA (SERPINF1) were determined via Western blotting and reverse transcription-polymerase chain reaction, respectively. Immunohistochemical staining for Ki-67 and CD34 was performed to calculate keratinocyte proliferation index (PI) and microvessel density (MVD), respectively. RESULTS: Levels of both PEDF protein and SERPINF1 mRNA were significantly lower in lesions from patients with condyloma acuminatum (n = 30) than in skin from healthy control subjects (n = 30). There were significant negative correlations between PEDF levels and both PI and MVD. CONCLUSIONS: The reduction in PEDF levels in condyloma acuminatum was associated with an increase in angiogenesis and cell proliferation. PEDF may be involved in the pathogenesis of condyloma acuminatum.