Molecular subgroups of adult medulloblastoma: a long-term single-institution study

Background Recent transcriptomic approaches have demonstrated that there are at least 4 distinct subgroups in medulloblastoma (MB); however, survival studies of molecular subgroups in adult MB have been inconclusive because of small sample sizes. The aim of this study is to investigate the molecular subgroups in adult MB and identify their clinical and prognostic implications in a large, single-institution cohort. Methods We determined gene expression profiles for 13 primary adult MBs. Bioinformatics tools were used to establish distinct molecular subgroups based on the most informative genes in the dataset. Immunohistochemistry with subgroup-specific antibodies was then used for validation within an independent cohort of 201 formalin-fixed MB tumors, in conjunction with a systematic analysis of clinical and histological characteristics. Results Three distinct molecular variants of adult MB were identified: the SHH, WNT, and group 4 subgroups. Validation of these subgroups in the 201-tumor cohort by immunohistochemistry identified significant differences in subgroup-specific demographics, histology, and metastatic status. The SHH subgroup accounted for the majority of the tumors (62%), followed by the group 4 subgroup (28%) and the WNT subgroup (10%). Group 4 tumors had significantly worse progression-free and overall survival compared with tumors of the other molecular subtypes. Conclusions We have identified 3 subgroups of adult MB, characterized by distinct expression profiles, clinical features, pathological features, and prognosis. Clinical variables incorporated with molecular subgroup are more significantly informative for predicting adult patient outcome

Effect of siRNA interference on nerve growth factor in intervertebral disc inflammation rats

AbstractObjectiveTo investigate the inhibition effect of siRNA interference on NGF induced by inflammatory factor IL-6, and IL-1 so as to provide novel targets for clinical treatment of discogenic low back pain.MethodsThe intervertebral disc nucleus and annulus fibrosus cells of rats were separated. The cells were co-cultured with different concentrations (10 nmol/L, 20 nmol/L, 50 nmol/L, 100 nmol/L) of IL-6 and IL-1β. The NGF-siRNA was leaded into the co-cultured cells with its import ability assessed by flow cytometry instrument tests, before and after which the NGF mRNA expression was detected by real-time Q-PCR and the NGF content was detected by ELISA.ResultsFlow cytometry instrument test results showed that the NGF-siRNA cell conversion rate was 99.8%. Real-time Q-PCR detection results showed that compared with negative control group, the NGF mRNA expression of co-cultured cells treated by 10 nmol/L, 20 nmol/L, 50 nmol/L, 100 nmol/L IL-6 and IL-1β were respectively raised 3.4, 3.7, 4.7, 3.7 times which were all significantly down-regulated after the import of NGF-siRNA. EILSA detection results showed that compared with negative control group, the NGF content of co-cultured medium treated by 10 nmol/L, 20 nmol/L, 50 nmol/L, 100 nmol/L I-L6 and IL-1β were respectively raised 2.9, 3.3, 4.5, 7.4 times which were all significantly decreased after the import of NGF-siRNA.ConclusionsThese molecular biological results suggest that inflammatory factor IL-6 and IL-1β could stimulate NGF on intervertebral disc cells in vitro culture model and its efficiency is concentration dependent, while siRNA interference can inhibit the stimulation effect of IL-6 and IL-1β on intervertebral disc cell, which provides a new targets for the clinical treatment of discogenic low back pain

Comparative studies on the regulatory effects of raw and charred hawthorn on functional dyspepsia and intestinal flora

Purpose: To compare the effects of raw hawthorn (RH) and charred hawthorn (CH) on functional dyspepsia (FD) and intestinal flora (IF).Methods: A rat model of FD was established through use of a chronic stimulator. Rat models were evaluated by the rat’s physical state, body weight, diet, and histopathological examination. After RH or CH administration, the digestive function of the rats was evaluated by determining gastric emptying and intestinal propulsion rate, diversity of intestinal flora.Results: RH and CH both improved gastric emptying and intestinal propulsion rate in FD group when compared to control group (p < 0.05). CH yielded higher treatment effectiveness than RH. Sixteen phyla of microbiomes were recognized from all samples. After FD model establishment, the relative abundance of Lactobacillus, Lachnospiraceae and Bacteroidales decreased compared to normal control rats. On the other hand, the relative abundance of Helicobacter and Bacteroides in the model control group increased compared to normal control. After RH and CH treatment, the relative abundance of all dysregulated phyla was restored to varying degrees, but the levels after CH treatment were similar to those of the normal control group.Conclusion: The relative abundance of intestinal flora of FD model rats is significantly different from that of rats in normal control group. Thus, RH and CH intervention improves digestive function, and the mechanisms may be related to adjustment of gut dysbacteriosis.Keywords: Raw Hawthorn, Charred Hawthorn, Functional dyspepsia, Intestinal flor

Mutation of SLC35D3 causes metabolic syndrome by impairing dopamine signaling in striatal D1 neurons

We thank Dr. Ya-Qin Feng from Shanxi Medical University, Dr. Tian-Yun Gao from Nanjing University and Dr. Yan-Hong Xue from Institute of Biophysics (CAS) for technical assistance in this study. We are very thankful to Drs. Richard T. Swank and Xiao-Jiang Li for their critical reading of this manuscript and invaluable advice. Funding: This work was partially supported by grants from National Basic Research Program of China (2013CB530605; 2014CB942803), from National Natural Science Foundation of China 1230046; 31071252; 81101182) and from Chinese Academy of Sciences (KSCX2-EW-R-05, KJZD-EW-L08). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD