LGG Group Research Articles

Synbiotic effects of Lactobacillus rhamnosus fermented with different prebiotics on the digestive enzyme activities, SCFAs and intestinal flora of Macrobrachium rosenbergii in vitro

Synbiotics are combinations of probiotics and prebiotics. It has been shown to be beneficial to aquatic animals. In this study, Lactobacillus rhamnosus was cultured with different prebiotics as the sole carbon source, including inulin, acanthopanax senticosus polysaccharide (ASPS), chitosan oligosaccharide (COS), saposhnikovia divaricata polysaccharide (SDP), polysaccharide of atractylodes macrocephala koidz (PAMK), astragalus polysaccharides (APS), Yu-Ping-Feng polysaccharide (YPFP), xylooligosaccharides (XOS) and mannose (MAN). Screening and gradient experiments revealed that the suitable prebiotics and concentrations were: 2 % MAN, 3 % APS, 3 % YPFP, 4 % PAMK, 3 % SDP. L. rhamnosus (108 CFU/mL) and suitable prebiotics were inoculated into the media supplemented with the intestinal chyme of Macrobrachium rosenbergii. Based on the preliminary screening experiment with the gradients. The in vitro fermentation experiment comprised seven groups: a control group (CT); L. rhamnosus group (LGG); L. rhamnosus + 2 % MAN group (LGG+MAN); L. rhamnosus + 3 % APS group (LGG+APS); L. rhamnosus + 3 % YPFP group (LGG+YPFP); L. rhamnosus + 4 % PAMK group (LGG+PAMK); L. rhamnosus + 3 % SDP group (LGG+SDP). The in vitro fermentation results revealed that the amylase activity was significantly increased in LGG+PAMK, LGG+SDP and LGG+APS groups than in the CT group (P<0.05). The LGG+MAN group showed the highest protease activity (P<0.05), while the activity of lipase was significantly greater in the LGG and LGG+YPFP groups than in the CT group (P<0.05). Moreover, the acetic acid and valeric acid contents were significantly increased in the LGG+PAMK, LGG+YPFP and LGG+SDP groups than in the CT and LGG groups (P<0.05). Additionally, the LGG+APS, LGG+PAMK, LGG+YPFP and LGG+SDP treatments significantly decreased the abundance of Aeromonas (P<0.05). Lactobacillus was more abundant in the LGG+YPFP group than in the other groups (P<0.05). In general, based on in vitro fermentation of M. rosenbergii intestine, the combination of L. rhamnosus with 3 % YPFP is the optimal synbiotic for the prawn.

STEM-04. BIOBANKING PATIENT-DERIVED MODELS OFFERS A PRECISE SPATIAL AND EPIGENETIC APPROACH TO UNRAVEL THE INITIATION, PROGRESSION, AND THERAPEUTIC RESISTANCE OF PEDIATRIC BRAIN TUMORS

Abstract BACKGROUND Aggressive brain cancers represent the most lethal forms of tumors in pediatric population. Their molecular drivers and co-alterations are currently guiding therapeutic strategies. Due to heterogeneous nature of these tumors, they are quickly developing resistance to treatment. Recognizing intrinsic and extrinsic mechanisms underlying therapeutic resistance, international scientific community has recognized an urgent need to create precise models of brain tumors capable of predicting therapeutic responses. So far, patient-derived cell lines (PDCL) remain the most reliable model to estimate and mimic evolving scenarios. The primary challenges lie in derivation methods and in cellular and spatial validation. METHODS In the context of the PEDIAMODECAN program, we collected 105 fresh brain tumor samples, including 34 LGG, 24 HGG, 19 ependymomas, 19 medulloblastomas, and 9 other rare entities, to concurrently generate PDCLs and patient-derived xenografts (PDX). RESULTS Regarding the derivation process itself, we successfully maintained 80% of samples in 2D and 54% in PDX models. As anticipated, the LGG group showed the higher percentage of PDX failure (90%). Nevertheless, for high-grade subtypes, PDX generation rate increased to 85,7%. No correlation was found between derivation success and a shorter interval between surgical removal and dissociation processes. Histological analysis of PDXs models confirmed the similar microscopic features to those of primary tumors. Next-Generation Sequencing (NGS), methylome assays and spatial transcriptomic analyses of derived models matched those of the original patient tumors. Epigenetic approaches were proved to be the most effective methods for validating models, in addition to spatial transcriptomic analyses that highlighted similar inter-tumor heterogeneity between PDX models and primary tumor counterparts. CONCLUSIONS Establishing a systematic PDCL/PDX biobank for all pediatric brain tumors represents one of the most effective approaches to develop models capable of accurately reproducing tumoral heterogeneity, histological and molecular diversity, and facilitating the design predictive screenings for targeted therapies combined with irradiation.

QOL-17. SLEEP QUALITY DIMENSIONS IN LOW AND HIGH-GRADE GLIOMA SURVIVORS

Abstract In this study, we examined the relationship between sleep disturbance and tumor grades in a group of low-grade (LGG; grade I-II) and high-grade glioma (HGG; grade III-IV) survivors &amp;lt; 1 to 10+ years from initial diagnosis. 42 glioma survivors completed the Pittsburgh Sleep Quality Index (PSQI). We examined frequency of poor sleep quality (defined as PSQI &amp;gt;5) and compared global PSQI between LGG and HGG groups. We obtained high-resolution T1 weighted images from a subset of 24 patients for gray matter volume analyses. The sample was predominantly male (66%) and Caucasian (82%). Of the 42 participants, 31% (n = 13) had LGG and 69% (n = 29) had HGG. 60% (n = 25) of all participants had poor sleep quality, with no differences observed between LGG and HGG. There were no differences between groups in age, education, measures of depression and anxiety, or general health-related quality of life (MOS SF-36). A Mann-Whitney U test indicated that there was no significant difference in global PSQI scores between LGG (Mdn = 4) and HGG groups (Mdn = 6), U = 239, p = .254. Sleep quality was not associated with time since diagnosis for either LGG (r = .108, p = .724) and HGG groups (r=-.058, p = .762). Whole brain vertex-wise comparison revealed smaller gray matter volumes in patients with poor sleep quality versus good sleep quality in the isthmus cingulate, cuneus, and precuneus of the left hemisphere (p &amp;lt; 0.05). Our analyses suggest that sleep quality is important to assess in glioma survivors of any grade and at any time since diagnosis. Poor sleep in glioma survivorship could be associated with structural differences in brain regions sensitive to sleep problems in other populations. Given the high rate of sleep disturbance, further study is warranted to better understand risk and develop targeted interventions.

Lactobacillus rhamnosus GG aggravates vascular calcification in chronic kidney disease: A potential role for extracellular vesicles

AimsLactobacillus rhamnosus GG (LGG) is a probiotic with great promise in future clinical application, which can significantly promote bone formation. However, the effect of LGG on CKD-related vascular calcification is unclear. In this study, we aimed to investigate the effect of LGG on CKD-related vascular calcification. Materials and methodsAfter 2 weeks of 5/6 nephrectomy, CKD rats received a special diet (4 % calcium and 1.8 % phosphate) combined with 1,25-dihydroxyvitamin D3 to induce vascular calcification. Meanwhile, CKD rats in the LGG group were gavaged orally with LGG (1 × 109 CFU bacteria/day). 16S RNA amplicon sequencing was performed to analyze the effect of LGG treatment on gut microbiota composition. Furthermore, differential ultracentrifugation was utilized to extract EVs. The effects of EVs on vascular calcification were evaluated in rat VSMCs, rat aortic rings, and CKD rat calcification models. In this study, vascular calcification was assessed by microcomputed tomography analysis, alizarin red staining, calcium content determination, and the expression of osteogenic transcription factors RUNX2 and BMP2. Key findingsLGG remarkably aggravated vascular calcification. LGG supplementation significantly altered gut microbiota composition in CKD rats, particularly increasing Lactobacillus. Interestingly, EVs presented a significant promoting effect on the development of calcification. Finally, mechanistic analysis proved that EVs aggravated vascular calcification through PI3K/AKT signaling. SignificanceThese results do not support the supplementation of LGG in CKD-associated vascular calcification patients. Our study presented a fresh perspective on LGG with potential risks and adverse effects. CKD patients should use specific probiotic strains cautiously.

Machine learning-based identification of SOX10 as an immune regulator of macrophage in gliomas.

Gliomas, originating from the glial cells, are the most lethal type of primary tumors in the central nervous system. Standard treatments like surgery have not significantly improved the prognosis of glioblastoma patients. Recently, immune therapy has become a novel and effective option. As a conserved group of transcriptional regulators, the Sry-type HMG box (SOX) family has been proved to have a correlation with numerous diseases. Based on the large-scale machine learning, we found that the SOX family, with significant immune characteristics and genomic profiles, can be divided into two distinct clusters in gliomas, among which SOX10 was identified as an excellent immune regulator of macrophage in gliomas. The high expression of SOX10 is related to a shorter OS in LGG, HGG, and pan-cancer groups but benefited from the immunotherapy. It turned out in single-cell sequencing that SOX10 is high in neurons, M1 macrophages, and neural stem cells. Also, macrophages are found to be elevated in the SOX10 high-expression group. SOX10 has a positive correlation with macrophage cytokine production and negative regulation of macrophages' chemotaxis and migration. In conclusion, our study demonstrates the outstanding cluster ability of the SOX family, indicating that SOX10 is an immune regulator of macrophage in gliomas, which can be an effective target for glioma immunotherapy.

Surgical techniques and function outcome for cingulate gyrus glioma, how we do it.

ObjectiveCingulate cortex and cingulum both play crucial roles in limbic system. The aim of study is to observe and analyze surgical outcomes of cingulate gyrus glioma through extents of resection (EORs), overall survival (OS), and postsurgical neurological outcome.MethodThe authors retrospectively studied 95 consecutive adult cases of primary cingulate gliomas that all underwent craniotomies and tumor resection. The patients were classified into unitary sub-region based on the four-division model. The information of clinical symptoms, pathology, EOR, postoperative neurological outcome and survival were analyzed through group comparison.ResultLow-grade gliomas (LGGs) were more prevalent (69.47%) for cingulate gyrus. Diffuse astrocytoma (40.00%) was most common histopathological diagnosis in total. Regarding sub-regions tumor involved in, midcingulate cortex (MCC) glioma was most prevalent (54.74%) followed by anterior cingulate cortex (ACC) glioma. Among all patients, 83 patients (87.37%) received EOR ≥ 90%. In LGG group, 58 patients (87.88%) received EOR ≥ 90%. The achievement of EOR significantly correlated with survival (P = 0.006). MCC cases were significantly associated with short-term morbidity in either language or motor function (P = 0.02). Majority of ACC cases (80.65%) escaped from any short-term deficits and nearly 90% free for permanent morbidity. Tumors in the dominant hemisphere were significantly associated with language dysfunction or cognition dysfunction, either short-term (P=0.0006) or long-term morbidity (P=0.0111). Age was the only postoperative susceptible predictor for all types of transient (P=0.021) and permanent (P=0.02) neurological deficit.ConclusionRegarding cingulate gyrus glioma, the management of surgical plans could be carried out into four sub-region level. In spite of short-term neurological dysfunction caused by surgical procedure, majority of transient dysfunction could be relieved or recovered in long-term. The necessary effort to prolong overall survival is still to achieve advisable EOR.

Integrative Genomic and Transcriptomic Analysis of Primary Malignant Gliomas Revealed Different Patterns Between Grades and Somatic Mutations Related to Glioblastoma Prognosis.

Background: As reflected in the WHO classification of glioma since 2020, genomic information has been an important criterion in addition to histology for glioma classification. There is a significant intergrade difference as well as intragrade difference of survival probability among glioma patients. Except the molecular criteria used in the WHO classification, few studies have explored other genomic factors that may be underlying these survival differences, especially in Chinese populations. Here, we used integrative genomic approaches to characterize a Chinese glioma cohort to search for potential prognostic biomarkers. Methods: We recruited 46 Chinese patients with primary malignant glioma. All the patients were analyzed with whole-exome sequencing (WES) and 27 of them were analyzed with RNA-seq. We compared the molecular features between patients in different WHO grades. We classified the glioblastoma (GBM) patients into two groups (good vs poor survival) using six-month progression-free survival (PFS6) status and compared the genomic profiles between the two groups. Results: We found grade II and grade III patients cluster together (LGG) and they are different from GBM in unsupervised clustering analysis with RNA-seq data. Gene set enrichment analysis (GSEA) comparing GBM and the LGG group suggested that GBM had upregulation of multiple pathways related to genome integrity and immune cell infiltration. Further comparison of somatic mutations between the two groups revealed TOPAZ1 as a novel mutation associated with GBM and prevalence of CNV in multiple genes in GBM. Comparison between PFS6 good and poor GBM patients revealed six genes (TRIML2, ROCK1, PKD1, OBSCN, HECTD4, and ADCY7) were significantly mutated and two genes (NTRK1 and B2M) had more CNV alterations in the poor prognosis group. Conclusion: Taken together, our molecular data revealed that GBM patient showed distinct characteristics related to individual gene, chromosome integrity, and infiltrating immune cells compared to LGG (grade II/III) patients. We also identified few novel genes with SNV or CNV, which might be the potential markers for clinical outcome of GBM.

Hydrogen Proton Magnetic Resonance Spectroscopy (MRS) in Differential Diagnosis of Intracranial Tumors: A Systematic Review.

Meningioma, glioma, and metastases are the most common intracranial tumors in clinical practice. In order to improve the prognosis of patients, timely diagnosis and early treatment are crucial. Hydrogen proton magnetic resonance spectroscopy (1H-MRS) imaging can noninvasively display the biochemical information of tissues in vivo and has been applied to identify and diagnose intracranial tumors. We want to comprehensively evaluate 1H-MRS identify and diagnose intracranial tumors by meta-analysis. Some databases such as PubMed and Cochrane Library were used to systematically search articles that were about identifying and diagnosing intracranial tumors with 1H-MRS. Then, weighted mean difference (WMD) was used as an effect size to conduct meta-analysis. There are altogether nine articles, including 533 patients. Results of meta-analysis: The Cho/Cr and Cho/NAA ratios in the LGG group were significantly lower than those in the HGG group (WMD = −0.69, 95% CI (−0.92, −0.45), P < 0.001, WMD = −0.76, 95% CI (−1.03, −0.48), P < 0.001). The Cho/Cr ratio of tumor and peritumor in the HGG group was significantly different from that in the metastasis group (0.68, 95% CI (−1.27, 2.62), P < 0.001, WMD = 0.94, 95% CI (0.41, 1.47), P < 0.001). There was no significant difference in the tumor and peritumor NAA/Cr ratio between the HGG group and metastasis group (WMD = −0.64, 95% CI (−1.63, 0.34), P=0.31, WMD = −0.22, 95% CI (−0.59, 0.15), P=0.24). 1H-MRS can provide metabolic information of different intracranial tumors and can effectively diagnose and differentiate glioma and metastasis. 1H-MRS can also provide a reliable basis for the classification of glioma, and has certain clinical application value.

Investigation of the Relationship Between the Degree of Peritumoral Brain Edema and Pathological Features of Glioma Before Surgery

Background: Gliomas are the most common malignant tumors of the central nervous system (CNS). Preoperative prediction of the malignancy grade of gliomas are of particular importance. These tumors are often accompanied by peritumoral brain edema (PTBE). Previous studies have suggested that the degree of PTBE is an independent indicator of the prognosis of gliomas. Objectives: This study aimed to investigate the relationships between the degree of PTBE and the grade of glioma, isocitrate dehydrogenase 1 (IDH1) mutation status, and Ki-67 expression level in gliomas. Patients and Methods: In this retrospective cross-sectional study, a total of 82 patients were enrolled, according to the 2016 World Health Organization (WHO) classification of CNS tumors. Overall, 29 tumors were pathologically confirmed as low-grade gliomas (LGGs , grade I-II), whereas the remaining 53 tumors were classified as high-grade gliomas (HGGs, grade III-IV). The IDH1 mutations, Ki-67 expression, and magnetic resonance imaging (MRI) findings were retrospectively analyzed. The tumor and tumor + PTBE volumes were also measured, and the tumor edema index (EI) was calculated for each patient. Edema was then graded and correlated with the pathological parameters. Results: The degree of EI was higher in the HGG group compared to the LGG group, and the difference was statistically significant (z = -7.018, P &lt; 0.05). Besides, the degree of EI was higher in the IDH1 wild-type compared with mutant groups (z = -4.116, P &lt; 0.05). The degree of EI significantly associated with Ki-67 expression and patient’s age (P &lt; 0.05), whereas there was no significant association between the degree of EI and gender (z = -0.497, P = 0.619). The Spearman’s correlation test revealed that the EI degree was positively correlated with the Ki-67 expression level and age, with correlation coefficients of 0.740 and 0.466, respectively. Moreover, the multivariate logistic regression analysis indicated that EI and IDH1 had significant effects on differentiating LGGs from HGGs (P &lt; 0.05 for both). The receiver operating characteristic (ROC) curve analysis showed that EI was an optimal index for differentiating LGGs from HGGs, with an area under curve (AUC) of 0.822 (cutoff value: 1.722, sensitivity: 95.8%, specificity: 70.0%, 95% CI: 0.718 - 0.899). Conclusion: The degree of PTBE was found to be a valuable index for the differential diagnosis of LGGs from HGGs. It has a significant difference between IDH1 wild and mutation status, furthermore, it was positively correlated with the age and Ki-67 level.

Assessment of Lactobacillus casei rhamnosus (LGG) therapy in children with biliary atresia – Randomized placebo controlled trial

BackgroundThe role of microbiota in biliary atresia (BA) remains unclear. The aim of our study was to assess efficacy and safety of LGG treatment in children with BA after HPE with special focus on bacterial cholangitis (BCH) and quantitative assessment of the gut microbiota composition and metabolism. MethodsWe performed double-blind placebo controlled trial with patients randomized into treatment group who received LGG (n = 14) and placebo (n = 16). The gut microbiota and short-chain fatty acids (SCFA) were assessed at baseline and after 6 months of treatment. Clinical and laboratory parameters including episodes of bacterial cholangitis (BCH) were collected during the study period and after 2-year follow-up. Additionally, stool composition of BA patients was compared with healthy age-matched control group. ResultsThere were lower concentration of SCFA in children with BA compared to control group and significant increase in the number of Enterococcus bacteria. After 6 months of treatment, neither laboratory parameters nor gut microbiota composition differed between LGG group and placebo. PP analysis results were similar to ITT analysis, no significant differences between study and control group. Overall, there were 11 (36%) patients who developed at least one episode of bacterial cholangitis; 3 (21%) in the LGG group compared to 8 (50%) placebo group (p = 0.14). Bacterial cultures were positive in 22% of cases and recurrence after the first episode was observed in 27% of patients. The level of total bilirubin decreased below 2 mg/dl after 6 months of the study in 6 (42.8%) patients in the LGG group and in 8 (50%) patients in the placebo group (p = 0.73). During 2-year follow-up 6 out of 14 patients (42.8%) in the LGG group and 11 out of 16 placebo patients (68.7%) underwent liver transplantation (p = 0.27). ConclusionsPatients with BA present with specific microbiota profiles and decreased SCFA what gives opportunities to implement novel therapeutic options based on modulation of microbiota. Whether LGG is an effective therapy needs to be studied in a larger group with similar outcome parameters.

Diagnostic performance of diffusion tensor imaging for preo- perative glioma grading.

This study aimed to determine the diagnostic per-formance of fractional anisotropy (FA) and mean diffusivity (MD) values for glioma grading. The tMD, rMDt/w, and rFAp/w values represent useful indices for the differentiation between LGG and HGG. The combination of these indices can improve diagnostic specificity. A total of 42 patients who underwent biopsy or surge-ry and were histologically diagnosed with glioma from September 2019 to December 2020 were enrolled in this retrospective study. Diffusion tensor imaging (DTI) and conventional magnetic resonance imaging (MRI) were performed preoperatively using 3 Tesla MRI in all cases. The FA and MD values were measured in the solid portion of the tumor, the peritumoral area, and the normal white matter. The diagnostic performances of the absolute and relative FA and MD values for glioma grading were analyzed using the receiver operating characteristic (ROC) curve. The MD value in the solid portion of the tumor (tMD), the MD value of the solid portion of the tumor relative to that in the normal white matter (rMDt/w), and the FA value for the peritumoral region relative to that of the normal white matter (rFAp/w) showed significant differences between the low-grade (LGG) and high-grade glioma (HGG) groups. The combination of these three parameters provided the largest area under the curve value of 89% with sensitivity, specificity, accuracy, negative predictive, and positive predictive values of 72%, 100%, 81%, 62%, and 100%, respectively, for distinguishing between the LGG and HGG groups.

Ferroptosis-related gene signature predicts prognosis and immunotherapy in glioma.

AimsGlioma is a highly invasive brain tumor, which makes prognosis challenging and renders patients resistant to various treatments. Induction of cell death is promising in cancer therapy. Ferroptosis, a recently discovered regulated cell death, can be induced for killing glioma cells. However, the prognostic prediction of ferroptosis‐related genes (FRGs) in glioma remains elusive.MethodsThe mRNA expression profiles and gene variation and corresponding clinical data of glioma patients and NON‐TUMOR control were downloaded from public databases. Risk score based on a FRGs signature was constructed in REMBRANDT cohort and validated in other datasets including CGGA‐693, CGGA‐325, and TCGA.ResultsOur results demonstrated that the majority of FRGs was differentially expressed among GBM, LGG, and NON‐TUMOR groups (96.6%). Furthermore, the glioma patients with low‐risk score exhibited a more satisfactory clinical outcome. The better prognosis was also validated in the glioma patients with low‐risk score no matter to which grade they were affiliated. Functional analysis revealed that the high‐risk score group was positively correlated with the enrichment scores for immune checkpoint blockade‐related positive signatures, indicating the critical role of glioma immunotherapy via risk score.ConclusionA novel FRGs‐related risk score can predict prognosis and immunotherapy in glioma patients.

Inflow-based vascular-space-occupancy (iVASO) might potentially predict IDH mutation status and tumor grade in diffuse cerebral gliomas

PurposeThe aim of the study is to assess the diagnostic performance of inflow-based vascular-space-occupancy (iVASO) MR imaging for differentiating glioblastomas (grade IV, GBM) and lower-grade diffuse gliomas (grade II and III, LGG) and its potential to predict IDH mutation status. MethodsOne hundred and two patients with diffuse cerebral glioma (56 males; median age, 43.5 years) underwent iVASO and dynamic susceptibility contrast (DSC) MR imaging. The iVASO-derived arteriolar cerebral blood volume (CBVa), relative CBVa (rCBVa), and the DSC-derived relative cerebral blood volume (rCBV) were obtained, and these measurements were compared between the GBM group (n = 43) and the LGG group (n = 59) and between the IDH-mutation group (n = 54) and the IDH-wild group (n = 48). ResultsSignificant correlation was observed between rCBV and CBVa (P < 0.001) or rCBVa (P < 0.001). Both CBVa (P < 0.001) and rCBVa (P < 0.001) were higher in the GBM group. Both CBVa (P < 0.001) and rCBVa (P < 0.001) were lower in the IDH-mutation group compared to the IDH-wild group. Receiver operating characteristic analyses showed the area under curve (AUC) of 0.95 with CBVa and 0.97 with rCBVa in differentiating GBM from LGG. The AUCs were 0.82 and 0.85 for CBVa and rCBVa in predicting IDH gene status, respectively, which were lower than that of rCBV (AUC = 0.90). Combined rCBV and rCBVa significantly improved the diagnostic performance (AUC = 0.95). ConclusionsiVASO MR imaging has the potential to predict IDH mutation and grade in glioma.

Combined application of MRS and DWI can effectively predict cell proliferation and assess the grade of glioma: A prospective study

In order to assess combined application of MRS and DWI for prediction cell proliferation and grade diagnosis of glioma, We prospectively collected the Cho/Cr, Cho/NAA, Cr/NAA of MRS and tumor parenchyma ADC (ADCT), contralateral mirror brain tissue ADC (ADCH), rADC (rADC = ADCT/ADCH). According to postoperative pathology, the patients were divided into two groups: LGG group and HGG group, compared differences of age, gender, Ki67, MRS, DWI between two groups. Next, we analyzed the correlation between MRS, DWI and Ki67. On this basis, the sensitivity and specificity of MRS, DWI and MRS combined with DWI (MRS + DWI) in diagnosis of glioma grade were evaluated. The differences of Ki67, Cho/Cr, Cho/NAA, Cr/NAA, ADCT, rADC between LGG group and HGG group were statistically significant (p = 0.000, 0.000, 0.000, 0.008, 0.000, and 0.000 respectively). From ROC curve, area under the curve (AUC), sensitivity and specificity of Cho/Cr, Cho/NAA, Cr/NAA, ADCT, rADC, PRE (MRS + DWI) were (0.901, 86.7%, 85.7%), (0.876, 80.0%, 82.1%), (0.704, 63.3%, 71.4%), (0.862, 82.1%, 83.3%), (0.820, 75.0%, 76.7%), (0.920, 86.7%, 89.3%), respectively. Fisher's linear discriminant functions results suggest: Y1 = -20.447 + 3.46•X1 + 17.141•X2 (LGG), Y2 = -19.415 + 4.828•X1 + 14.543•X2 (HGG). Our study suggested that MRS and DWI can effectively predict cell proliferation preoperative. MRS combined with DWI can further improve sensitivity and specificity in assessing the grade of glioma.

NI-01 Usefulness of preoperative evaluation of glioma elasticity by the magnetic resonance elastography

Introduction: The elasticity of intracranial tumors is difficult to assess non-invasively because the lesion is surrounded by the skull. Therefore, intracranial tumors have not been verified before surgery in terms of elastic modulus. Magnetic resonance elastography (MRE) is an epoch-making method capable of non-invasively imaging the elasticity of internal organs. We have examined the elasticity of meningiomas and pituitary adenomas and reported their usefulness. This time, we measured the glioma elasticity and verified usefulness of MRE.Method: Twenty-four gliomas (mean age 51.8±15.7 years, male: female = 17: 7) who underwent tumor resection after MRE imaging from July 2017 to May 2020 were targeted. The average elasticity was measured as an evaluation of tumor elastic modulus by MRE. Gliomas were divided into a low-grade glioma group (LGG: Grade 1, 2) and a high-grade glioma group (HGG: Grade 3, 4). Then, a comparative statistical study was conducted.Results: The average values of the average elasticity of LGG group (9 cases) and HGG group (15 cases) were 1.8±0.8 kPa and 2.5±0.8 kPa, respectively. The average elasticity was significantly higher in the HGG group (p=0.023). In the ROC analysis, the cutoff value was 2.1 kPa (sensitivity 70%, specificity 70%). Therefore, it was suggested that the tumor is likely to be HGG when the average elasticity is 2.1 kPa or more.Discussion: The glioma elasticity by preoperative MRE was significantly higher in the HGG group. Based on actual surgical experience, the tumor seems to be hard in the HGG group, and it was judged to be consistent with this our MRE research. The preoperative evaluation of glioma elasticity by MRE was considered useful, and it might help in planning a surgical strategy considering malignant grade.

Alleviation and recovery effects of Lactobacillus on the antibiotic-induced intestinal dysbiosis in early life stages of mice

To investigate the effects of Lactobacillus on the alleviation and recovery of ceftriaxone-induced intestinal dysbiosis in early life stages of mice, and the possible effect on immunity of the host. A total of 48 four-week-old Balb/c male mice were randomly divided into four groups, with 12 in each group. The experiment lasted for four weeks. In the first week, mice were given normal saline, ceftriaxone, ceftriaxone plus Lactobacillus rhamnosus GG, ceftriaxone plus direct vat set pickle(PC) by gavage respectively in the control group(ctrl), ceftriaxone group(ceftri), PC group and LGG group. The PC group and LGG group were given PC and LGG respectively for the last three weeks. The feces were collected once a week, and the profile composition of fecal bacteria were analyzed by next-generation sequencing. The mRNA expression levels of interleukin-6(IL-6), IL-12 and tumor necrosis factor α(TNF-α) in the spleen were analysed using quantitative real-time PCR. In the first week, the simpson index decreased significantly in the ceftri group(P&lt;0. 001), but not in PC and LGG groups. At week four, the observed-species index in the PC group increased significantly(P&lt;0. 001) and the simpson index increased in both LGG group and ceftri group(P&lt;0. 01). As for the flora structure, in the first week, the ctrl group differed from the other three groups significantly(P&lt;0. 05) while no differences were found between the PC group and the LGG group. The firmicutes/bacteroides(F/B) ratio of three ceftriaxone-treated groups increased while the abundance of Akkermansia decreased, particularly in the ceftri group. In the fourth week, the intestinal flora structure were different between four groups(P&lt;0. 05) and the F/B ratio and Akkermansia abundance recovered. Ruminococcaceae, Bacteroidaceae and Tannerellacea appeared in the ceftri group, while Lactobacillus was dominant in the PC group, and Akkermansia was the characteristic species of the LGG group. Weight lost was found in ceftriaxone-treated groups(P&lt;0. 05) and the PC group recovered first. IL-12 and TNF-α mRNA expression of the spleen were lower in PC and LGG groups compared with the ceftri group(P&lt;0. 01). IL-6 mRNA expression level in the LGG group were lower than the ctrl group(P&lt;0. 01). The administration of antibiotics in the early life stage might inhibit weight gain, reduce the diversity of intestinal flora, damage functional bacteria and cause long-term inflammation, even though self-recovery ability exist. Lactobacillus might be helpful to alleviate the damage of antibiotics. But no therapeutic effect has been found.

The regulatory effect of Lactobacillus rhamnosus GG on T lymphocyte and the development of intestinal villi in piglets of different periods

The maturation and development of T cells were not completed until T cells were selected in thymus. It was not until the early 1960s that j.f.a.p. discovered the importance of thymus in T cell development. Twelve healthy piglets were randomly divided into two groups, the experimental group (LGG group) and the control group (saline group). The LGG group piglets were given 1 ml LGG (6 × 109 CFU/ml) per day. The saline group was given 1 ml of normal saline per day. The piglets were slaughtered at 30 days and 45 days, respectively, and the MLN, jejunum and ileum PPs, LP of the piglets were taken. The expression of CD3+CD4+ T lymphocytes was detected by flow cytometry, and intestinal villi development was observed by intestinal paraffin section. The results showed that the flow cytometry results at 30 days and 45 days showed that the CD3+CD4+ T lymphocytes in the MLN group were significantly different from those in the saline group (P < 0.05, P < 0.01).The CD3+CD4+ T lymphocytes in the jejunum PP of piglets in LGG group were significantly different from those in saline group (P < 0.05). The CD3+CD4+ T lymphocytes in the ileum PP of the LGG group were significantly different from those in the saline group (P < 0.05, P < 0.01). CD3+CD4+ T lymphocytes and normal saline in the piglets of the LGG group There was a significant difference between the two groups (P < 0.001, P < 0.05). P < 0.001). HE staining results showed the length of the LGG group ileal villi in piglets at 30 days, 45 days was significantly different from that in normal saline group (P < 0.01, P < 0.01). LGG can also regulate the proliferation of T lymphocytes in the intestine of early weaned piglets at 30 days and 45 days increase the number of CD3+CD4+ T lymphocytes.

Randomized controlled trial on the influence of dietary intervention on epigenetic mechanisms in children with cow\u2019s milk allergy: the EPICMA study

Epigenetic mechanisms could drive the disease course of cow’s milk allergy (CMA) and formula choice could modulate these pathways. We compared the effect of two different dietary approaches on epigenetic mechanisms in CMA children. Randomized controlled trial on IgE-mediated CMA children receiving a 12-month treatment with extensively hydrolyzed casein formula containing the probiotic L.rhamnosus GG (EHCF + LGG) or with soy formula (SF). At the baseline, after 6 and 12 months of treatment FoxP3 methylation rate and its expression in CD4+ T cells were assessed. At same study points IL-4, IL-5, IL-10, and IFN-γ methylation rate, expression and serum concentration, miRNAs expression were also investigated. 20 children (10/group) were evaluated. Baseline demographic, clinical and epigenetic features were similar in the two study groups. At 6 and 12 months, EHCF + LGG group showed a significant increase in FoxP3 demethylation rate compared to SF group. At the same study points, EHCF + LGG group presented a higher increase in IL-4 and IL-5 and a higher reduction in IL-10 and IFN-γ DNA methylation rate compared to SF group. A different modulation of miR-155, -146a, -128 and -193a expression was observed in EHCF + LGG vs. SF. Dietary intervention could exert a different epigenetic modulation on the immune system in CMA children.

Writing fluency in patients with low-grade glioma before and after surgery.

BackgroundLow‐grade glioma (LGG) is a type of brain tumour often situated in or near areas involved in language, sensory or motor functions. Depending on localization and tumour characteristics, language or cognitive impairments due to tumour growth and/or surgical resection are obvious risks. One task that may be at risk is writing, both because it requires intact language and memory function and because it is a very complex and cognitively demanding task. The most commonly reported language deficit in LGG patients is oral lexical‐retrieval difficulties, and poor lexical retrieval would be expected to affect writing fluency.AimsTo explore whether writing fluency is affected in LGG patients before and after surgery and whether it is related to performance on tasks of oral lexical retrieval.Methods & ProceduresTwenty consecutive patients with presumed LGG wrote a narrative and performed a copy task before undergoing surgery and at 3‐month follow‐up using keystroke‐logging software. The same tasks were performed by a reference group (N = 31). The patients were also tested using the Boston Naming Test (BNT) and word‐fluency tests before and after surgery. Writing fluency was compared between the patients and the reference group, and between the patients before and after surgery. Relationships between performance on tests of oral lexical retrieval and writing fluency were investigated both before and after surgery.Outcome & ResultsDifferent aspects of writing fluency were affected in the LGG patients both before and after surgery. However, when controlling for the effect of typing speed, the LGG group differed significantly from the reference group only in the proportion of pauses within words. After surgery, a significant decline was seen in production rate and typing speed in the narrative task, and a significant increase was seen in pauses before words. Strong positive relationships were found between oral lexical retrieval and writing fluency both before and after surgery.Conclusions & ImplicationsAlthough aspects of writing fluency were affected both before and after surgery, the results indicate that typing speed is an important factor behind the pre‐surgery differences. However, the decline in overall productivity and the increase in pauses before words after surgery could be related to a lexical deficit. This is supported by the finding that oral lexical‐retrieval scores were strongly correlated with writing fluency. However, further exploration is needed to identify the language and cognitive abilities affecting writing processes in LGG patients.

Optimal differentiation of high- and low-grade glioma and metastasis: a meta-analysis of perfusion, diffusion, and spectroscopy metrics.

To perform a meta-analysis of advanced magnetic resonance imaging (MRI) metrics, including relative cerebral blood volume (rCBV), normalized apparent diffusion coefficient (nADC), and spectroscopy ratios choline/creatine (Cho/Cr) and choline/N-acetyl aspartate (Cho/NAA), for the differentiation of high- and low-grade gliomas (HGG, LGG) and metastases (MTS). For systematic review, 83 articles (dated 2000-2013) were selected from the NCBI database. Twenty-four, twenty-two, and eight articles were included respectively for spectroscopy, rCBV, and nADC meta-analysis. In the meta-analysis, we calculated overall means for rCBV, nADC, Cho/Cr (short TE-from 20 to 35 ms, medium-from 135 to 144 ms), and Cho/NAA for the HGG, LGG, and MTS groups. We used random effects model to obtain weighted averages and select thresholds. Overall means (with 95% CI) for rCBV, nADC, Cho/Cr (short and medium echo time, TE), and Cho/NAA were: for HGG 5.47 (4.78-6.15), 1.38 (1.16-1.60), 2.40 (1.67-3.13), 3.27 (2.78-3.77), and 4.71 (3.24-6.19); for LGG 2.00 (1.71-2.28), 1.61 (1.36-1.87), 1.46 (1.20-1.72), 1.71 (1.49-1.93), and 2.36 (1.50-3.23); for MTS 5.06 (3.85-6.27), 1.35 (1.06-1.64), 1.89 (1.72-2.06), 3.14 (1.57-4.72), (Cho/NAA was not available). LGG had significantly lower rCBV, Cho/Cr, and Cho/NAA values than HGG or MTS. No significant differences were found for nADC. Best differentiation between HGG and LGG is obtained from rCBV, Cho/Cr, and Cho/NAA metrics. MTS could not be reliably distinguished from HGG by the methods investigated.