Imbalance in the Gut Microbiota of Children With Autism Spectrum Disorders.

Background: Autism spectrum disorder (ASD) are complex behavioral changes manifesting early in childhood, which impacts how an individual perceives and socializes with others. The study aims to assess the disparities in gut microbiota (GM) amongst healthy controls and children with ASD. Methods: The study was performed on 25 children with ASD and 20 healthy children. Autistic symptoms were diagnosed and assessed with the Diagnostic and Statistical Manual for Mental Disorders and the Autism Treatment Evaluation Checklist (ATEC). Gastrointestinal (GI) symptoms were assessed with a GI Severity Index (GSI) questionnaire. The fecal bacteria composition was investigated by the high-throughput sequencing of the V3-V4 region of the 16S rRNA gene. The alpha diversity was estimated using the Shannon, Chao, and ACE indexes. The unweighted UniFrac analysis and the PCA plots were used to represent the beta diversity. LDA and LEfSe were used to assess the effect sizes of each abundant differential taxon. Results: Children with high GSI scores had much higher ATEC Total scores than those with lower GSI-scores. GI symptoms were strongly associated with symptoms of ASD. There was no difference in Chao, ACE, and Shannon indexes between ASD patients and healthy controls. Both groups showed a significant microbiota structure clustering in the plotted PCAs and significant differences in its composition at the family, order, genus, and phyla levels. There were also noteworthy overall relative differences in Actinobacteria and Firmicutes between both groups. Conclusions: This study shows the relationship between the clinical manifestations of Autistic symptoms and GI symptoms. ASD patients have dysbiosis of gut microbiota, which may be related to the onset of ASD. These findings may be beneficial for developing ASD symptoms by changing gut microbiota.

Effects of probiotics combined with early enteral nutrition on endothelin-1 and C-reactive protein levels and prognosis in patients with severe traumatic brain injury.

OBJECTIVE: To investigate the effects of probiotics combined with early enteral nutrition on levels of endothelin-1 (ET-1), C-reactive protein (CRP), and inflammatory factors, and on the prognosis of patients with severe traumatic brain injury (TBI). METHODS: We enrolled 76 adults with severe TBI. The patients were divided randomly into two equal groups administered enteral nutrition with and without probiotics, respectively. Demographic and clinical data including age, sex, Glasgow Coma Scale score, Sequential Organ Failure Score, Acute Physiology, Chronic Health Score, hospitalization, mortality, and infections were recorded. RESULTS: Serum levels of inflammatory factors gradually decreased with increasing treatment time in both groups. However, ET-1 at 15 days, and interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α, and CRP at 7 and 15 days decreased significantly more in the combined treatment group. Hospitalization duration and pulmonary infection rates were also significantly reduced in the combined compared with the enteral nutrition alone group. GCS scores at 15 days were significantly lower in the combined compared with the enteral nutrition group. CONCLUSION: Probiotics combined with early enteral nutrition could reduce serum levels of ET-1, CRP, and IL-6, IL-10, and TNF-α, and could thus improve the recovery of patients with severe TBI.

A genetic variant in COL11A1 is functionally associated with lumbar disc herniation in Chinese population.

This study aimed to explore whether the genetic variant of COL11A1 is functionally associated with the development of lumbar disc herniation (LDH) in Chinese population. SNP rs1676486 of COL11A1 was genotyped in 647 patients and 532 healthy controls. The differences of genotype and allele distributions between LDH patients and healthy controls were evaluated using the χ² test. One-way ANOVA test was used to compare the relationship between genotypes and clinical features including tissue expression of COL11A1 and the degree of disc degeneration. Patients were found to have a significantly higher frequency of TT than the controls (10.2% versus 7.3%, P = 0.004). Besides, the frequency of allele T was found to be remarkably higher in the patients than the controls (34.8% versus 28.1%, P < 0.001) with an odds ratio of 1.36 (95% confidential interval=1.14-1.63). Patients with genotype TT were found to have remarkably more severe disc degeneration (P = 0.02). Besides, the expression of COL11A1 in the lumbar disc was significantly lower in the patients with genotype TT than in those with genotype CT or CC (P < 0.001). Moreover, the expression level was inversely correlated with the severity of disc degeneration (P < 0.001). We confirmed that the rs1676486 of COL11A may be functionally associated with LDH in the Chinese population. Extracellular matrix related proteins may play an important role in the pathogenesis of LDH. Our findings shed light on a better understanding of the pathogenesis of LDH, which could be a promising target for a novel treatment modality of LDH.

Risk of Stroke in Patients with Herpes Zoster: A Systematic Review and Meta-Analysis.

BACKGROUND: Several observational studies suggest that herpes zoster (HZ) may increase the risk of stroke, but the results are inconsistent. Our study was designed to assess the association between HZ and the risk of stroke through a meta-analysis of cohort studies. METHODS: The electronic databases PubMed and EMBASE were searched from inception to May 31, 2016 to identify relevant cohort studies that assess the risk of stroke in patients with HZ. Reference lists were also reviewed to identify potential studies. The random-effects model and fixed-effects model were used to calculate the summary relative risks (RRs) with 95% confidence intervals (CIs). RESULTS: Six cohort studies (251,076 HZ patients and 8462 cases of stroke) were identified in the study. The result showed that HZ was significantly correlated with increased risk of stroke, and the pooled RR was 1.36 (95% confidence interval [CI]: 1.10, 1.67) (P = .004). In the subgroup analysis, the significant association was observed except for stroke type (hemorrhage group). In the sensitivity analysis, excluding 1 study, the pooled RR was 1.45 (95% CI: 1.17, 1.80) (P = .001) for HZ, and 4.42 (95% CI: 2.75, 7.11) (P = .000) for herpes zoster ophthalmicus. Considerable heterogeneity was observed in our study. CONCLUSION: Our study furnishes evidence of a positive association between HZ and the risk of stroke.

Transplantation of placenta-derived mesenchymal stem cells reduces hypoxic-ischemic brain damage in rats by ameliorating the inflammatory response.

Hypoxic-ischemic brain damage (HIBD) is a common cause of infant death. The purpose of our research was to explore the immunoregulatory mechanism of placenta-derived mesenchymal stem cells (PD-MSCs) in HIBD treatment. Seven-day-old rat pups were randomly divided into HIBD, PD-MSC, fibroblast, and control groups. Forty-eight hours after HIBD induction, cells at a density of 5 × 104 cells/10 µl were injected into the cerebral tissue in the PD-MSC and fibroblast groups. The TNF-α, interleukin- 17 (IL-17), interferon-γ (IFN-γ), and IL-10 levels were detected through quantitative real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Regulatory T cell (Tregs) populations were detected through flow cytometry, and forkhead box P3 (Foxp3) was measured through western blot analysis. Behavioral tests and gross and pathological examinations showed that PD-MSC treatment exerted significantly stronger neuroprotective effects than the other treatments. The expression levels of pro-inflammatory cytokines were substantially upregulated after HI injury. Compared with fibroblast treatment, PD-MSC treatment inhibited the production of pro-inflammatory cytokines and increased the production of IL-10 in the ischemic hemispheres and peripheral blood serum (all P < 0.01). Flow cytometry results showed a notable increase in the number of Tregs within the spleen of the HIBD group. Moreover, the number of Tregs and the Foxp3 expression levels were higher in the PD-MSC treatment group than in the HIBD and fibroblast groups (all P < 0.01). Our research suggests that the mechanism of PD-MSC treatment for HIBD partially involves inflammatory response suppression.

Therapeutic effect of placenta-derived mesenchymal stem cells on hypoxic-ischemic brain damage in rats.

BACKGROUND: Oxidative stress is involved in the development of hypoxic-ischemic brain damage (HIBD). In this study, we investigated the therapeutic effects of placenta-derived mesenchymal stem cells (PD-MSCs) and explored the NF-E2-related factor-2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway in treating HIBD. METHODS: P7 rats were subjected to hypoxic-ischemic brain injury and randomly divided into four groups (control, HIBD, HIBD+PD-MSCs, and HIBD+fibroblasts). Forty-eight hours after the induction of HIBD, 5×10(5) of PD-MSCs were injected into cerebral tissue in the HIBD+PD-MSCs group, while the same dose of fibroblasts were injected in the HIBD+fibroblasts group. Morris Water Maze, gross and pathological changes were tested at P28. The level of malondialdehyde (MDA) was detected in rats' hippocampus. RT-PCR and western blot analysis were used to evaluate the changes of Nrf2/HO-1. RESULTS: The HIBD group showed significantly longer escape latency and a lower frequency of original platform crossing in the Morris Water Maze compared with the control group. Rats receiving PD-MSCs showed significant improvement of HIBD. The pathological changes were evident after HIBD, but ameliorated in the PD-MSCs group. Compared with the control group, HO-1 and Nrf2 were up-regulated at gene and protein levels in the HI brain, beginning at 6 hours and peaking at 48 hours (P<0.05). The expression of HO-1 and Nrf2 in the PD-MSCs treatment group was more pronounced than in the HIBD group (P<0.01). PD-MSCs also decreased MDA production in the brain tissue. CONCLUSION: These results demonstrate that PD-MSCs have neuroprotective effect during the treatment of HIBD and that the mechanism may be partly due to alleviating oxidative stress.

[Changes of circulating IFN-gamma, IL-4 in patients with chronic periodontitis before and after periodontal initial therapy].

PURPOSE: To investigate the effect of periodontal initial therapy on circulating blood serum interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) in patients with chronic periodontitis. METHODS: 15 patients with chronic periodontitis and 15 healthy people were selected. Circulating blood serum IFN-gamma and IL-4 were measured using double antibody sandwich ELISA; Student's t test was used for comparing sulcus bleeding index (SBI), probing depth (PD), and circulating IFN-gamma, IL-4 in patients with chronic periodontitis that were assessed respectively before and 4 to 6 weeks after periodontal initial therapy. RESULTS: The level of blood serum IFN-gamma, IL-4 in patients with chronic periodontitis was significantly higher than the control group (P<0.01); After periodontal initial therapy, SBI, PD, and circulating IFN-gamma concentration were reduced significantly (P<0.01); IL-4 concentration had no significant difference (P>0.05). CONCLUSIONS: Blood serum IFN-gamma, IL-4 were associated with chronic periodontitis; The control of gingival infection may reduce blood serum IFN-gamma concentration; IL-4 concentration was not reduced with the control of gingival infection. Periodontal initial therapy.