Bifidobacterium breve M-16V alters the gut microbiota to alleviate OVA-induced food allergy through IL-33/ST2 signal pathway.

There has been a marked increase in life-threatening food allergy (FA). One hypothesis is that changes in bacterial communities may be key to FA. To better understand how gut microbiota regulates FA in humans, we established a mouse model with FA induced by ovalbumin. We found that the mice with FA had abnormal bacterial composition, accompanied by increased immunoglobulin G, immunoglobulin E, and interleukin-4/interferon-γ, and there existed a certain coherence between them. Interestingly, Bifidobacterium breve M-16V may alter the gut microbiota to alleviate the allergy symptoms by IL-33/ST2 signaling. Our results indicate that gut microbiota is essential for regulating FA to dietary antigens and demonstrate that intervention in bacterial community regulation may be therapeutically related to FA.

Probiotics as a functional food ingredient in allergic diseases: regulation of CD4+ T helper cell differentiation.

Allergic diseases are increasing worldwide, associating with increased health costs and decreased quality of life. Allergy is immune-related diseases caused by an allergic immune response to innocuous substance in the environment. At present, research has focussed on the study of the relevance to the microbiome and the phenotypes of allergy, including the relationships among the gastrointestinal microbiome, immune function, and allergic sensitisation. Probiotics as functional food ingredient are thought to secrete functional metabolites that have antibacterial effects on ameliorating intestinal health and CD4+ T helper cells-mediated immunity. This review will summarise the role of probiotics in the immune regulation and flora balance, highlighting recent advances in our understanding of the imbalance of Th subsets and cytokine leading to the immunopathology of allergic reactions. Finally, we discussed the unresolved problems and future research directions in order to promote the clinical application of probiotics immunotherapy.

HDAC2 hyperexpression alters hippocampal neuronal transcription and microglial activity in neuroinflammation-induced cognitive dysfunction.

BACKGROUND: Inflammation can induce cognitive dysfunction in patients who undergo surgery. Previous studies have demonstrated that both acute peripheral inflammation and anaesthetic insults, especially isoflurane (ISO), are risk factors for memory impairment. Few studies are currently investigating the role of ISO under acute peri-inflammatory conditions, and it is difficult to predict whether ISO can aggravate inflammation-induced cognitive deficits. HDACs, which are essential for learning, participate in the deacetylation of lysine residues and the regulation of gene transcription. However, the cell-specific mechanism of HDACs in inflammation-induced cognitive impairment remains unknown. METHODS: Three-month-old C57BL/6 mice were treated with single versus combined exposure to LPS injected intraperitoneally (i.p.) to simulate acute abdominal inflammation and isoflurane to investigate the role of anaesthesia and acute peripheral inflammation in cognitive impairment. Behavioural tests, Western blotting, ELISA, immunofluorescence, qRT-PCR, and ChIP assays were performed to detect memory, the expressions of inflammatory cytokines, HDAC2, BDNF, c-Fos, acetyl-H3, microglial activity, Bdnf mRNA, c-fos mRNA, and Bdnf and c-fos transcription in the hippocampus. RESULTS: LPS, but not isoflurane, induced neuroinflammation-induced memory impairment and reduced histone acetylation by upregulating histone deacetylase 2 (HDAC2) in dorsal hippocampal CaMKII+ neurons. The hyperexpression of HDAC2 in neurons was mediated by the activation of microglia. The decreased level of histone acetylation suppressed the transcription of Bdnf and c-fos and the expressions of BDNF and c-Fos, which subsequently impaired memory. The adeno-associated virus ShHdac2, which suppresses Hdac2 after injection into the dorsal hippocampus, reversed microglial activation, hippocampal glutamatergic BDNF and c-Fos expressions, and memory deficits. CONCLUSIONS: Reversing HDAC2 in hippocampal CaMKII+ neurons exert a neuroprotective effect against neuroinflammation-induced memory deficits.

Study of disease phenotype and its association with prognosis of paediatric inflammatory bowel disease in China.

BACKGROUND: To investigate the unique features of inflammatory bowel disease (IBD) in children, we wanted to identify whether there might be a strong correlation between the disease phenotype and its prognosis at various ages in paediatric patients. METHODS: We collected data from patients diagnosed with IBD (ulcerative colitis (UC) or Crohn's disease (CD)) from 2002 to 2016. The diagnosis was made according to the Porto criteria and Paris Classification. Patient characteristics, clinical manifestations and treatments were collected. Risk factors for surgery, mortality and relapse were analysed by Cox proportional hazard models. RESULTS: Of the 143 patients, 113 had CD, and 30 had UC; there were 89 males and 54 females with a median age of 9 years (y). Thirteen patients in the 0-2 y group were identified as having mutations in IL-10 receptor A, and this mutation was significantly more common in this age group than in 3-9 and 10-16 y patients. The risk factor for surgery was the B3 phenotype; risk factors for death were age 0-2 y and B3 phenotype; 0-2 y, B3 phenotype and steroid dependency were risk factors for early relapse. CONCLUSIONS: Clinical manifestations of the onset of IBD in infants and toddlers were extensive and aggressive and were closely associated with early relapse and death. It is of particular interest that some of these patients developed IBD due to monogenic disorders; thus, introduction of genetic testing is essential for these patients.

A novel risk variant block across introns 36-45 of CACNA1C for schizophrenia: a cohort-wise replication and cerebral region-wide validation study.

OBJECTIVES: Numerous genome-wide association studies have identified CACNA1C as one of the top risk genes for schizophrenia. As a necessary post-genome-wide association study (GWAS) follow-up, here, we focused on this risk gene, carefully investigated its novel risk variants for schizophrenia, and explored their potential functions. METHODS: We analyzed four independent samples (including three European and one African-American) comprising 5648 cases and 6936 healthy subjects to identify replicable single nucleotide polymorphism-schizophrenia associations. The potential regulatory effects of schizophrenia-risk alleles on CACNA1C mRNA expression in 16 brain regions (n = 348), gray matter volumes (GMVs) of five subcortical structures (n = 34 431), and surface areas and thickness of 34 cortical regions (n = 36 936) were also examined. RESULTS: A novel 17-variant block across introns 36-45 of CACNA1C was significantly associated with schizophrenia in the same effect direction across at least two independent samples (1.8 × 10-4 ≤ P ≤ 0.049). Most risk variants within this block showed significant associations with CACNA1C mRNA expression (1.6 × 10-3 ≤ P ≤ 0.050), GMVs of subcortical structures (0.016 ≤ P ≤ 0.048), cortical surface areas (0.010 ≤ P ≤ 0.050), and thickness (0.004 ≤ P ≤ 0.050) in multiple brain regions. CONCLUSION: We have identified a novel and functional risk variant block at CACNA1C for schizophrenia, providing further evidence for the important role of this gene in the pathogenesis of schizophrenia.

An Assessment Framework for the Training of General Practitioners and Specialists Based on EPAs.

Purpose: The purpose of this study is to explore the practicality and feasibility of EPA (level 4 theory) for establishing medical training and service model in China. Method: We opted for a mixed qualitative and quantitative research method, considering both explanatory and exploratory sequential designs. The qualitative research comprehended focus groups and interviews conducted with two panels of experts. The quantitative research was conducted to collect data about the applicability of international entrustable professional activities (EPAs) pediatrics standards in the Chinese context by organizing a seminar with a sample of 60 pediatricians. A questionnaire was designed with EPAs and distributed within professional networks. Structural equation modeling and statistical analysis were used to process the data. Results: In this study, Medical Service-Groups Model (MSGM) with four levels was successfully established to measure the correlation between specialized and general EPAs. As expected, results showed that specialized EPAs were built on top of general EPAs. There may be a mediating mechanism that general EPAs contribute to the lower level of specialization EPAs. In addition, levels 1 and 2 were primarily needed to lay the groundwork for levels 3 and 4, and these higher levels of EPAs were still the most informative for specialized Gastroenterology EPAs. Conclusions: The diagnosis and treatment level of primary general practitioners, as the basis of the pediatric medical service chain, affected the clinical disposal ability of specialists. The establishment of MSGM provided a theoretical basis for the linkage training of general practitioners and specialist physicians. In future studies, scholars must explore China's EPAs based on unique national conditions.

Effects of endocrine disrupting chemicals in host health: Three-way interactions between environmental exposure, host phenotypic responses, and gut microbiota.

Endocrine disrupting chemicals (EDCs) have gradually become a global health hazard in recent decades. Gut microbiota (GM) provides a crucial interface between the environment and the human body. A triad relationship may exist between EDCs exposure, host phenotypic background, and GM effects. In this review, we attempted to parse out the contribution of GM on the alteration of host phenotypic responses induced by EDCs, suggesting that GM intervention may be used as a therapeutic strategy to limit the expansion of pathogen. These studies can increase the understanding of pathogenic mechanisms, and help to identify the modifiable environmental factors and microbiota characteristics in people with underlying disease susceptibility for prevention and remediation.

ELECTRON ABSORBED FRACTIONS IN AN IMAGE-BASED MICROSCOPIC SKELETAL DOSIMETRY MODEL OF CHINESE ADULT MALE.

Based on the Chinese reference adult male voxel model, a set of microscopic skeletal models of Chinese adult male is constructed through the processes of computed tomography (CT) imaging, bone coring, micro-CT imaging, image segmentation, merging into macroscopic bone model and implementation in Geant4. At the step of image segmentation, a new bone endosteum (BE) segmentation method is realized by sampling. The set of model contains 32 spongiosa samples with voxel size of 19 µm cubes. The microscopic spongiosa bone data for Chinese adult male are provided. Electron absorbed fractions in red bone marrow (RBM) and BE are calculated. Source tissues include the bone marrow (red and yellow), trabecular bone (surfaces and volumes) and cortical bone (surfaces and volumes). Target tissues include RBM and BE. Electron energies range from 10 keV to 10 MeV. Additionally, comparison of the result with other investigations is provided.

Physical Dosimetric Reconstruction of a Radiological Accident at Nanjing (China) for Clinical Treatment Using Thudose.

A severe radiological accident involving an industrial radiography source containing Ir occurred in China. A worker was seriously exposed, which resulted in acute radiation syndrome. Initial whole-body dose was estimated at 1.51 Gy (95% Confidence Interval: 1.40-1.61 Gy) using biological dosimetry. This work performed a physical dosimetric reconstruction to provide more detailed exposure information for clinical treatment, using sitting and standing posture phantoms constructed by adjusting the Chinese reference adult male polygon surface phantoms to the worker body. A 3D view of photon flux in the body and dose distribution of local tissue with isodose lines in his legs were displayed by THUDose, and the absorbed doses of organs were present. These results were compatible with clinical symptoms and analysis, and they were helpful in assisting in the planning of therapy and in alerting physicians of potential high-risk organs. The physical dosimetric reconstruction could provide more detailed information for clinical treatment in a radiological accident with respect to obtaining local dose estimates.

ERp29 inhibits tumorigenicity by suppressing epithelial mesenchymal transition in gastric cancer.

ERp29 is a novel endoplasmic reticulum (ER) protein that plays an important role in protein unfolding and secretion. Recently, it has been reported to be widely implicated in control of tumorigenesis in some tumors. However, the potential function of ERp29 in gastric cancer remains poorly understood. In this study, we found that the positive rate of ERp29 in gastric cancer tissues was significantly lower than that in adjacent non-tumor tissues. And tumor with high ERp29 expression had inclinations towards smaller tumor size and earlier TNM stage. The in vitro experiments indicated that over-expression of ERp29 in gastric cancer cells significantly suppressed the proliferation and migration of tumor cells, which is consistent with the result of the in vivo animal experiments. Furthermore, our mechanistic investigations revealed that ERp29 reversed EMT process in gastric carcinoma, and its effect was related to the inactivation of ERK1/2 and AKT phosphorylation. Thus, we conclude that ERp29 acts as a tumor suppressor gene in gastric cancer, and is expected to become a novel target of the treatment of GC.