Acute Appendicitis as the Initial Presentation of Kawasaki Disease Shock Syndrome in Children.

Kawasaki disease shock syndrome (KDSS) is a severe form of Kawasaki disease (KD). The hemodynamic instability and atypical manifestations of this syndrome delay its correct diagnosis and timely treatment. We report here an eight-year-old girl who presented with appendicitis. Her fever persisted after appendectomy, accompanied by hemodynamic instability. The girl was diagnosed with KDSS. Intravenous immunoglobulin (IVIG) and corticosteroids were administered. Her symptoms resolved. She had left coronary artery dilatation, which resolved three months later. We also reviewed two other possible cases identified as KDSS with appendicitis. These cases have a more atypical clinical course, prolonged treatment, and a higher rate of IVIG resistance. Better awareness of KDSS is needed for early diagnosis and treatment in children experiencing prolonged fever after appendectomy.

Atomistic Insights into the Droplet Size Evolution during Self-Microemulsification.

Microemulsions have been attracting great attention for their importance in various fields, including nanomaterial fabrication, food industry, drug delivery, and enhanced oil recovery. Atomistic insights into the self-microemulsifying process and the underlying mechanisms are crucial for the design and tuning of the size of microemulsion droplets toward applications. In this work, coarse-grained models were used to investigate the role that droplet sizes played in the preliminary self-microemulsifying process. Time evolution of liquid mixtures consisting of several hundreds of water/surfactant/oil droplets was resolved in large-scale simulations. By monitoring the size variation of the microemulsion droplets in the self-microemulsifying process, the dynamics of diameter distribution of water/surfactant/oil droplets were studied. The underlying mass transport mechanisms responsible for droplet size evolution and stability were elucidated. Specifically, temperature effects on the droplet size were clarified. This work provides the knowledge of the self-microemulsification of water-in-oil microemulsions at the nanoscale. The results are expected to serve as guidelines for practical strategies for preparing a microemulsion system with desirable droplet sizes and properties.

Clinical characterization and immunosuppressive regulation of CD161 (KLRB1) in glioma through 916 samples.

BACKGROUND: Glioblastoma is a paradigm of cancer-associated immunosuppression, limiting the effects of immunotherapeutic strategies. Thus, identifying the molecular mechanisms underlying immune surveillance evasion is critical. Recently, the preferential expression of inhibitory natural killer (NK) cell receptor CD161 on glioma-infiltrating cytotoxic T cells was identified. Focusing on the molecularly annotated, large-scale clinical samples from different ethnic origins, the data presented here provide evidence of this immune modulator's essential roles in brain tumor biology. METHODS: Retrospective RNA-seq data analysis was conducted in a cohort of 313 patients with glioma in the Chinese Glioma Genome Atlas (CGGA) database and 603 patients in The Cancer Genome Atlas (TCGA) database. In addition, single-cell sequencing data from seven surgical specimens of glioblastoma patients and a model in which patient-derived glioma stem cells were cocultured with peripheral lymphocytes, were used to analyze the molecular evolution process during gliomagenesis. RESULTS: CD161 was enriched in high-grade gliomas and isocitrate dehydrogenase (IDH)-wildtype glioma. CD161 acted as a potential biomarker for the mesenchymal subtype of glioma and an independent prognostic factor for the overall survival (OS) of patients with glioma. In addition, CD161 played an essential role in inhibiting the cytotoxicity of T cells in glioma patients. During the process of gliomagenesis, the expression of CD161 on different lymphocytes dynamically evolved. CONCLUSION: The expression of CD161 was closely related to the pathology and molecular pathology of glioma. Meanwhile, CD161 promoted the progression and evolution of gliomas through its unique effect on T cell dysfunction. Thus, CD161 is a promising novel target for immunotherapeutic strategies in glioma treatment.

TREM2 is associated with tumor immunity and implies poor prognosis in glioma.

Triggering receptor expressed on myeloid cells 2 (TREM2) is expressed in myeloid cells of the central nervous system (CNS), which mediate the immunological response in a variety of diseases. Uncertain is the function of TREM2 in glioma and tumor immune responses. In this research, the expression patterns of TREM2 in glioma were analyzed, along with its prognostic value and functional roles. TREM2 expression is increased in glioblastomas, gliomas with a mesenchymal subtype, gliomas with wild-type isocitrate dehydrogenase, and gliomas without 1p/19q deletion, all of which suggest the aggressiveness and poor prognosis of gliomas. Gene ontology, KEGG, and Gene set variation analyses indicated that TREM2 may serve as an immune response mediator. However, the function of T cells against tumor cells was negatively correlated with TREM2, suggesting that TREM2 may suppress tumor immunity. Further investigation demonstrated a correlation between TREM2 expression and immune checkpoint expression. CIBERSORT research revealed a link between a higher TREM2 expression level and the enrichment of tumor-associated macrophages, especially M2 subtype. Single-cell analysis and multiple immunohistochemical staining results showed that microglia and macrophage cells expressed TREM2. Immunofluorescent staining indicated that knocking down the expression of TREM2 would result in a decrease in M2 polarization. TREM2 was discovered to be an independent prognostic factor in glioma. In conclusion, our findings revealed that TREM2 was significantly expressed in microglia and macrophage cells and was intimately associated with the tumor immune microenvironment. Thus, it is expected that small-molecule medications targeting TREM2 or monoclonal antibodies would enhance the efficacy of glioma immunotherapy.

Molecular Characterization and Clinical Relevance of ANXA1 in Gliomas via 1,018 Chinese Cohort Patients.

Annexin A1 (ANXA1) is a calcium-dependent phospholipid-binding protein and has been implicated in multiple functions essential in cancer, including cell proliferation, apoptosis, chemosensitivity, metastasis, and invasion. However, the biological role and clinical behavior of ANXA1 in glioma remain unclear. In this study, RNA-seq (n = 1018 cases) and whole-exome sequencing (WES) (n = 286 cases) data on a Chinese cohort, RNA-seq data with different histological regions of glioblastoma blocks (n = 270 cases), and scRNA-seq data (n = 7630 cells) were used. We used the R software to perform statistical calculations and graph rendering. We found that ANXA1 is closely related to the malignant progression in gliomas. Meanwhile, ANXA1 is significantly associated with clinical behavior. Furthermore, the mutational profile revealed that glioma subtypes classified by ANXA1 expression showed distinct genetic features. Functional analyses suggest that ANXA1 correlates with the immune-related function and cancer hallmark. At a single-cell level, we found that ANXA1 is highly expressed in M2 macrophages and tumor cells of the mesenchymal subtype. Importantly, our result suggested that ANXA1 expression is significant with the patient's survival outcome. Our study revealed that ANXA1 was closely related to immune response. ANXA1 plays a key factor in M2 macrophages and MES tumor cells. Patients with lower ANXA1 expression levels tended to experience improved survival. ANXA1 may become a valuable factor for the diagnosis and treatment of gliomas in clinical practice.

Galectin-9/TIM-3 as a Key Regulator of Immune Response in Gliomas With Chromosome 1p/19q Codeletion.

Gliomas with chromosome 1p/19q codeletion were considered a specific tumor entity. This study was designed to reveal the biological function alterations tightly associated with 1p/19q codeletion in gliomas. Clinicopathological and RNA sequencing data from glioma patients were obtained from The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases. Gene set variation analysis was performed to explore the differences in biological functions between glioma subgroups stratified by 1p/19q codeletion status. The abundance of immune cells in each sample was detected using the CIBERSORT analytical tool. Single-cell sequencing data from public databases were analyzed using the t-distributed stochastic neighbor embedding (t-SNE) algorithm, and the findings were verified by in vitro and in vivo experiments and patient samples.We found that the activation of immune and inflammatory responses was tightly associated with 1p/19q codeletion in gliomas. As the most important transcriptional regulator of Galectin-9 in gliomas, the expression level of CCAAT enhancer-binding protein alpha in samples with 1p/19q codeletion was significantly decreased, which led to the downregulation of the immune checkpoints Galectin-9 and TIM-3. These results were validated in three independent datasets. The t-SNE analysis showed that the loss of chromosome 19q was the main reason for the promotion of the antitumor immune response. IHC protein staining, in vitro and in vivo experiments verified the results of bioinformatics analysis. In gliomas, 1p/19q codeletion can promote the antitumor immune response by downregulating the expression levels of the immune checkpoint TIM-3 and its ligand Galectin-9.

Unraveling Adhesion Strength between Gas Hydrate and Solid Surfaces.

Natural gas hydrate is a promising future energy source, but it also poses a huge threat to oil and gas production due to its ability to deposit within and block pipelines. Understanding the atomistic mechanisms of adhesion between the hydrate and solid surfaces and elucidating its underlying key determining factors can shed light on the fundamentals of novel antihydrate materials design. In this study, large-scale molecular simulations are employed to investigate the hydrate adhesion on solid surfaces, especially with focuses on the atomistic structures of intermediate layer and their influences on the adhesion. The results show that the structure of the intermediate layer formed between hydrate and solid surface is a competitive equilibrium of induced growth from both sides, and is regulated by the content of guest molecules. By comparing the fracture behaviors of the hydrate-solid surface system with different intermediate structures, it is found that both the lattice areal density of water structure and the adsorption of guest molecules on the interface together determine the adhesion strength. Based on the analysis of the adhesion strength distribution, we have also revealed the origins of the drastic difference in adhesion among different water structures such as ice and hydrate. Our simulation indicates that ice-adhesion strength is approximately five times that of lowest hydrate adhesion strength. This finding is surprisingly consistent with the available experimental results.

YTHDF2 facilitates UBXN1 mRNA decay by recognizing METTL3-mediated m6A modification to activate NF-κB and promote the malignant progression of glioma.

BACKGROUND: The prognosis for diffuse gliomas is very poor and the mechanism underlying their malignant progression remains unclear. Here, we aimed to elucidate the role and mechanism of the RNA N6,2'-O-dimethyladenosine (m6A) reader, YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), in regulating the malignant progression of gliomas. METHODS: YTHDF2 mRNA levels and functions were assessed using several independent datasets. Western blotting, quantitative polymerase chain reaction, and immunohistochemistry were used to evaluate the expression levels of YTHDF2 and other molecules in human and mouse tumor tissues and cells. Knockdown and overexpression were used to evaluate the effects of YTHDF2, methyltransferase-like 3 (METTL3), and UBX domain protein 1 (UBXN1) on glioma malignancy in cell and orthotopic xenograft models. RNA immunoprecipitation (RIP), methylated RIP, and RNA stability experiments were performed to study the mechanisms underlying the oncogenic role of YTHDF2. RESULTS: YTHDF2 expression was positively associated with a higher malignant grade and molecular subtype of glioma and poorer prognosis. YTHDF2 promoted the malignant progression of gliomas in both in vitro and in vivo models. Mechanistically, YTHDF2 accelerated UBXN1 mRNA degradation via METTL3-mediated m6A, which, in turn, promoted NF-κB activation. We further revealed that UBXN1 overexpression attenuated the oncogenic effect of YTHDF2 overexpression and was associated with better survival in patients with elevated YTHDF2 expression. CONCLUSIONS: Our findings confirmed that YTHDF2 promotes the malignant progression of gliomas and revealed important insight into the upstream regulatory mechanism of NF-κB activation via UBXN1 with a primary focus on m6A modification.

A potentially effective drug for patients with recurrent glioma: sermorelin.

BACKGROUND: Treatment insensitivity is the main cause of glioma. This study was designed to screen out effective drugs for recurrent gliomas based on the transcriptomics data. METHODS: A total of 1,018 glioma patients with transcriptome sequencing data and clinical data were included in this study. There were 325 patients in the discovery cohort, including 229 primary patients and 92 recurrent patients. There were 693 patients in the validation cohort, including 422 primary patients and 271 relapsed patients. Drug Resistant Scores (DRS) of 4,865 drugs of each patient were used for screening. The analysis and drawing in this study were mainly based on R language. RESULTS: After high-throughput drug screening, we found that recurrent glioma patients were most sensitive to sermorelin. Further analysis revealed that sermorelin was suitable for recurrent patients with high grade, IDH-wildtype and 1p/19q non-codeletion status. GO and KEGG analyses found that sermorelin may inhibit tumor cell proliferation by cell cycle blocking. Moreover, sermorelin was also related to the immune system process and negatively regulated immune checkpoints and M0 macrophages. Lastly, the Kaplan-Meier method showed the patient's benefit from sermorelin was independent of postoperative adjuvant treatment. CONCLUSIONS: Recurrent glioma patients are sensitive to sermorelin and it makes effect through glioma cells proliferation inhibiting and immune response enhancing.

Optimization of Process Parameters for Fabricating Polylactic Acid Filaments Using Design of Experiments Approach.

The amount of wasted polylactic acid (PLA) is increasing because 3D printing services are an increasingly popular offering in many fields. The PLA is widely employed in the fused deposition modeling (FDM) since it is an environmentally friendly polymer. However, failed prototypes or physical models can generate substantial waste. In this study, the feasibility of recycling PLA waste plastic and re-extruded it into new PLA filaments was investigated. An automatic PLA filament extruder was first developed for fabricating new PLA filaments. This paper also discusses the process, challenges, and benefits of recycling PLA waste plastic in an effort to fabricate new PLA filaments more sustainable. It was found that it was possible to fabricate PLA filament using recycled PLA waste plastic. The production cost is only 60% of the commercially available PLA filament. The tensile strength of the developed PLA filament is approximately 1.1 times that of the commercially available PLA filament. The design of experiments approach was employed to investigate the optimal process parameters for fabricating PLA filaments. The most important control factor affecting the diameter of PLA filament is the barrel temperature, followed by recycled material addition ratio, extrusion speed, and cooling distance. The optimal process parameters for fabricating PLA filament with a diameter of 1.7 mm include the barrel temperature of 184 °C, extrusion speed of 490 mm/min, cooling distance of 57.5 mm, and recycled material addition ratio of 40%.

High-sensitive clinical diagnostic method for PTPRZ1-MET and the characteristic protein structure contributing to ligand-independent MET activation.

BACKGROUND: PTPRZ1-MET (ZM) is a critical genetic alteration driving the progression of lower-grade glioma. Glioma patients harboring ZM could benefit from MET inhibitors. According to the remarkable role of ZM as a driver of glioma progression and indicator of MET inhibitor sensitivity, it is necessary to detect this alteration even when it presents in glioma with relatively fewer copies. METHODS: Herein, we proposed that ZM could be detected with a high-sensitive method of reverse transcriptase PCR with 50 amplification cycles. Via this newly proposed detection method, we depicted the incidence preference of ZM fusion in a cohort of 485 glioma patients. To further explore the oncogenic nature of ZM, we predicated the protein structure alteration of MET kinase brought by its fusion partner. RESULTS: The incidence of ZM fusions was much higher than previous report. ZM fusions exhibited a striking preference in lower-grade glioma and secondary glioblastoma. By contrast, none of patients with primary glioblastoma was detected harboring ZM fusion. In each of the four variants of ZM, the fusion partner segment of MET contained a remarkable coiled-coil motif. In glioma cells expressing ZM, MET kinase could be activated in a ligand-independent manner, which might be contributed by the special coiled-coil structure brought by the fusion partner. Corresponding to the 3D structural analysis and cell line experiment, the ZM positive clinical specimens showed hyperactivations of MET signaling. CONCLUSIONS: ZM fusions are critical drivers of glioma progression and effective target of MET inhibitor. Early detection could be performed with a high-sensitive method of reverse transcriptase PCR. The hyperactivations of MET signaling driving glioma progression might be contributed by a ligand-independent activation enabled by the protein structure modification of extracellular domain of MET in ZM fusions.

Uronic acid metabolic process-related gene expression-based signature predicts overall survival of glioma.

Glioma is the most common and malignant cancer of the central nervous system, and the prognosis is poor. Metabolic reprogramming is a common phenomenon that plays an important role in tumor progression including gliomas. Searching the representative process among numerous metabolic processes to evaluate the prognosis aside from the glycolytic pathway may be of great significance. A novel prediction signature was constructed in the present study based on gene expression. A total of 1027 glioma samples with clinical and RNA-seq data were used in the present study. Lasso-Cox, gene set variation analysis, Kaplan-Meier survival curve analysis, Cox regression, receiver operating characteristic curve, and elastic net were performed for constructing and verifying predictive models. The R programming language was used as the main tool for statistical analysis and graphical work. This signature was found to be stable in prognostic prediction in the Chinese Glioma Genome Atlas Network and the Cancer Genome Atlas databases. The possible mechanism was also explored, revealing that the aforementioned signature was closely related to DNA replication and ATP binding. In summary, a prognosis prediction signature for patients with glioma based on five genes was constructed and showed great potential for clinical application.

A novel DNA repair-related nomogram predicts survival in low-grade gliomas.

AIMS: We aimed to create a tumor recurrent-based prediction model to predict recurrence and survival in patients with low-grade glioma. METHODS: This study enrolled 291 patients (188 in the training group and 103 in the validation group) with clinicopathological information and transcriptome sequencing data. LASSO-COX algorithm was applied to shrink predictive factor size and build a predictive recurrent signature. GO, KEGG, and GSVA analyses were performed for function annotations of the recurrent signature. The calibration curves and C-Index were assessed to evaluate the nomogram's performance. RESULTS: This study found that DNA repair functions of tumor cells were significantly enriched in recurrent low-grade gliomas. A predictive recurrent signature, built by the LASSO-COX algorithm, was significantly associated with overall survival and progression-free survival in low-grade gliomas. Moreover, function annotations analysis of the predictive recurrent signature exhibited that the signature was associated with DNA repair functions. The nomogram, combining the predictive recurrent signature and clinical prognostic predictors, showed powerful prognostic ability in the training and validation groups. CONCLUSION: An individualized prediction model was created to predict 1-, 2-, 3-, 5-, and 10-year survival and recurrent rate of patients with low-grade glioma, which may serve as a potential tool to guide postoperative individualized care.

Redox Regulator GLRX Is Associated With Tumor Immunity in Glioma.

Glutaredoxin is central to cellular redox chemistry and regulates redox homeostasis and malignant progression of many cancers. In glioma, the role of its coding gene (GLRX) remains unclear. We aimed to elucidate the role of glutaredoxin at the transcriptome level and its clinical prognostic value in glioma. In total, we evaluated 1,717 glioma samples with transcriptome data and corresponding clinical data as well as single-cell sequencing data from 6 glioma patients from publicly available databases. Gene set variation analysis and gene ontology analysis were performed to reveal the biological function of GLRX. The immune cell enrichment score was calculated by GSVA analysis. Single-cell sequencing data was visualized by t-distributed stochastic neighbor embedding analysis. The prognostic value of GLRX in glioma was verified by the Kaplan-Meier curve and multivariate COX analysis. GLRX was found to be highly enriched in gliomas of higher grades with wild-type IDH, without 1p/19q co-deletion, and with a methylated MGMT promoter. Moreover, GLRX could be a potential marker for the mesenchymal molecular subtype of gliomas. The expression of GLRX was closely related to the tumor immune process, immune checkpoints, and inflammatory factors with GLRX being specifically expressed in M0 macrophages. GLRX is also shown to be an independent prognostic factor in glioma. Altogether, our study outcomes show that GLRX is highly enriched in malignant gliomas and is closely related to the tumor immune microenvironment. Therefore, GLRX-targeted cell redox regulatory therapy may enhance the efficacy of glioma immunotherapy.

Single-Cell RNA-Sequencing Shift in the Interaction Pattern Between Glioma Stem Cells and Immune Cells During Tumorigenesis.

Glioblastoma is one of the most common neoplasms in the central nervous system characterized by limited immune response and unlimited expansion capability. Cancer stem cells (GSCs), a small fraction of the tumor cells, possess a pivotal regulation capability in the tumor microenvironment with a superior proliferation ability. We aimed to reveal the interaction between glioma stem cells (GSCs) and immune cells during tumorigenesis. Single-cell sequencing data from seven surgical specimens of glioblastoma patients and patient-derived GSCs cocultured with peripheral leukocytes were used for the analysis. Cell grouping and trajectory analysis were performed using Seurat and Monocle 3 packages in R software. The gene set of Cancer Genome Anatomy Project was used to define different cell types. Cells with the ability of proliferation and differentiation in glioblastoma tissue were defined as GSCs, which had a similar expression pattern to that in the GSCs in vitro. Astrocytes in glioblastoma were mainly derived from differentiated GSCs, while oligodendrocytes were most likely to be derived from different precursor cells. No remarkable evolutionary trajectory was observed among the subgroups of T cells in glioblastoma. The immune checkpoint interaction between GSCs and immune cells was changed from stimulatory to inhibitory during tumorigenesis. The patient-derived GSCs system is an ideal model for GSC research. The above research revealed that the interaction pattern between GSC glioma stem cells and immune cells during tumorigenesis provides a theoretical basis for GSC glioma stem cell-targeted immunotherapy.

A novel methylation signature predicts radiotherapy sensitivity in glioma.

Glioblastoma (GBM) is the most common and malignant cancer of the central nervous system, and radiotherapy is widely applied in GBM treatment; however, the sensitivity to radiotherapy varies in different patients. To solve this clinical dilemma, a radiosensitivity prediction signature was constructed in the present study based on genomic methylation. In total, 1044 primary GBM samples with clinical and methylation microarray data were involved in this study. LASSO-COX, GSVA, Kaplan-Meier survival curve analysis, and COX regression were performed for the construction and verification of predictive models. The R programming language was used as the main tool for statistical analysis and graphical work. Via the integration analysis of methylation and the survival data of primary GBM, a novel prognostic and radiosensitivity prediction signature was constructed. This signature was found to be stable in prognosis prediction in the TCGA and CGGA databases. The possible mechanism was also explored, and it was found that this signature is closely related to DNA repair functions. Most importantly, this signature could predict whether GBM patients could benefit from radiotherapy. In summary, a radiosensitivity prediction signature for GBM patients based on five methylated probes was constructed, and presents great potential for clinical application.

RPP30, a transcriptional regulator, is a potential pathogenic factor in glioblastoma.

BACKGROUND: Old age has been demonstrated to be a risk factor for GBM, but the underlying biological mechanism is still unclear. We designed this study intending to determine a mechanistic explanation for the link between age and pathogenesis in GBM. RESULTS: The expression of RPP30, an independent prognostic factor in GBM, was negatively correlated with age in both tumor and non-tumor brain samples. However, the post-transcriptional modifications carried out by RPP30 were different in primary GBM and non-tumor brain samples. RPP30 affected protein expression of cancer pathways by performing RNA modifications. Further, we found that RPP30 was related to drug metabolism pathways important in GBM. The decreased expression of RPP30 in older patients might be a pathogenic factor for GBM. CONCLUSION: This study revealed the role of RPP30 in gliomagenesis and provided the theoretical foundation for targeted therapy. METHODS: In total, 616 primary GBM samples and 41 non-tumor brain samples were enrolled in this study. Transcriptome data and clinical information were obtained from the CGGA, TCGA, and GSE53890 databases. Gene Set Variation Analysis and Gene Ontology analyses were the primary analytical methods used in this study. All statistical analyses were performed using R.

EFEMP2 indicates assembly of M0 macrophage and more malignant phenotypes of glioma.

Immune response mediated by macrophages is critical in tumor progression and implicates new targets in potential efficient immunotherapies. Tumor associated macrophages (TAM) are divided into either polarized M1 or M2 phenotype depending on different regulators of polarization and pro- or anti-oncogenic roles they play. Glioma-infiltrated TAMs have been newly reported contrary to the current polarization dogma. Instead, macrophages in glioma exhibit a continuum phenotype between the M1- and M2-like TAM that resembling M0 macrophage. Here we proposed an OS (overall survival)-correlated gene EFEMP2 (EGF containing fibulin-like extracellular matrix protein 2) via screening with transcriptional expression levels and methylation data in two glioma databases. EFEMP2 was found highly expressed in glioma of higher WHO grade and Mesenchymal subtype glioma, and its transcriptional level could predict OS efficiently in validation datasets. EFEMP2 exhibited a remarkable preference of intercellular expression. In vitro assay showed that EFEMP2's level in medium was closely related to glioma cells' growth. Moreover, EFEMP2 expression level was remarkably correlated with immunological responses. M0-like macrophage as a feature of malignancy of glioblastoma revealed distinct assembly in glioma with high level of EFEMP2. These results revealed EFEMP2's role as a potential characteristic marker of malignant glioma, which are enriched of M0 macrophage.

Modulations of probiotics on gut microbiota in a 5-fluorouracil-induced mouse model of mucositis.

BACKGROUND AND AIM: Intestinal mucositis remained one of the most deleterious complications in cancer patients undergoing chemotherapy. 5-FU treatment was reported to affect the abundance of gut microbiota and cause mucositis, which might be ameliorated by probiotics. We investigate the potential changes of 5-FU treatment and the modulations of probiotics on gut microbiota in a mouse model. METHODS: Male BALB/c mice received either 5-FU or saline (S). They were separated and fed saline, Lactobacillus casei variety rhamnosus (Lcr) and Lactobacillus reuteri DSM 17938 (BG). Lcr and BG were simultaneously administered with 5-FU for 5 days. Stool specimens were collected for DNA extraction and pyrosequenced for bioinformatic analysis. RESULTS: Fecal microbial communities were obviously diverse. Bacteroides and Bacteroidaceae were the most abundant microbiota in FU.BG group while S24_7 was the most in S.S group. At phylum and class levels, abundances of Betaproteobacteria, Erysipelotrichi, Gammaproteobacteria, and Verrucomicrobia were significantly increased in the FU groups. Probiotics supplementation did increase the abundances of Enterobacteriales and Turicibacterales. We demonstrated that probiotics did modulate the abundance and diversity of gut microbiota. Bacterial motility proteins were found enriched and upregulated in the S.BG group. No mortality was noted. No bacterial translocation was found in spleen and blood among the six groups. CONCLUSION: Gut microbiota of mice undergoing chemotherapy exhibited a distinct disruption in bacterial composition. Probiotic did modulate the abundance and diversity of gut microbiota. This is the first study to analyze the effects and safety of Lactobacillus strains on 5-FU-induced mucositis systematically and assess changes in the intestinal microbiota after probiotic intervention.

Postoperative standard chemoradiotherapy benefits primary glioblastoma patients of all ages.

BACKGROUND: Glioblastoma is the most malignant tumor of the central nervous system. Several prediction models have been produced to aid in prognosis assessment. Age, a primary decision factor for prognosis, is associated with increased genomic alterations, however the exact link between increased age and poor prognosis is unknown. OBJECTIVE: In this study, we aimed to reveal the underlying cause of poor prognosis in elderly patients. METHODS: This study included data on 616 primary GBM tumor samples from the CGGA and TCGA databases and 41 nontumor brain tissue samples obtained from GSE53890. Hallmarks and clinicopathological characteristics were evaluated in both tumor and nontumor brain tissues. The association between choice of treatment regimen and age was measured using ANOVA and Student's t test. RESULTS: Age was a robust predictor of poor prognosis in glioma. No age-related hallmarks of cancer were detected, including pathological characteristics or mutations. However, treatment choice was strongly significantly different between old and young patients. Combined chemo-radiation therapy could benefit old and young GBM patients, however, old patients are currently less likely to choose it. CONCLUSION: The vast divergence in prognosis between young and old GBM patients is largely caused by choice of treatment rather than age-related tumor genomic characteristics. Postoperative standard radio- and chemotherapy provide strong benefits to primary glioblastoma patients of all ages.