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Background: Immunotherapy provided unprecedented advances in the treatment of several previously untreated cancers. However, these immunomodulatory maneuvers showed limited response to patients with glioma in clinical trials. Our aim was to depict the immune characteristics of glioma with immune cytolytic activity at genetic and transcriptome levels. Methods: In total, 325 gliomas from CGGA dataset as training cohort and 699 gliomas from TCGA dataset as validation cohort were enrolled in our analysis. We calculated the immune cytolytic activity for 1,000 of gliomas. The characteristics of immune cytolytic activity in gliomas were interpreted by the corresponding clinical, molecular genetics and radiological information. Results: We found that immune cytolytic activity was highly associated with molecular, clinical, and edema extent. High cytolytic activity gliomas were more likely to be diagnosed as glioblastoma and might be a potential marker of mesenchymal subtype. Moreover, those gliomas exhibited significantly increased copy number alterations including recurrent focal amplifications of PDGFA and EGFR, as well as recurrent deletions of CDKN2A/B. Subsequent biological function analysis revealed that the immune response and immune checkpoints expression were significantly correlated with the cytolytic activity of gliomas. Immune cytolytic activity was significantly positively associated with the extent of peri-tumor edema and was independently correlated with reduced survival time. Conclusion: Our results highlighted the immunoregulatory mechanism heterogeneity of gliomas. Cytolytic activity, indirectly reflected by the extent of peri-tumor edema, may provide a potential index to evaluate the status of immune microenvironment and immune checkpoints in glioma, which should be fully valued for precision classification and immunotherapy. [ABSTRACT FROM AUTHOR]

Background: We identified an autophagy-inducing areca nut (AN) ingredient (AIAI) in the 30-100 kDa fraction of AN extract (ANE 30-100K). This study was to analyze the role of endocytosis in ANE 30-100K-induced autophagy.Methods: We used benzyl alcohol, dynasore, and shRNA of clathrin and dynamin to assess whether ANE 30-100K-induced cytotoxicity and accumulation of microtubule-associated protein 1 light chain 3 (LC3)-II were affected in oral (OECM-1) and esophageal (CE81T/VGH) carcinoma cells.Results: Both benzyl alcohol and dynasore effectively reduced ANE 30-100K-induced cytotoxicity and LC3-II accumulation in OECM-1 and CE81T/VGH cells. Downregulated protein expression of both clathrin and dynamin by their shRNA also significantly attenuated ANE 30-100K-induced elevation of LC3-II levels in CE81T/VGH cells.Conclusions: These results indicate that AIAI may be engulfed by cells through clathrin-mediated endocytosis, which promotes the execution of the following autophagy program. [ABSTRACT FROM AUTHOR]

Background: The combination of blue dye and radioisotope is most widely used to identify sentinel lymph nodes (SLNs) in patients with breast cancer. However, some individual studies suggested that dual tracers did not have an advantage over radioisotope alone in detecting SLNs. We performed a systematic review to investigate the added value of blue dye in addition to radioisotope.Methods: We searched Pubmed and Embase. Prospective studies that compared the combination of radioisotope and blue dye with radioisotope alone were selected. The identification rate of SLNs and the false-negative rate were the main outcomes of interest. The odds ratios (ORs) and 95% confidential intervals (CIs) were calculated by using random-effects model.Results: Twenty-four studies were included. The combination of radioisotope and blue dye showed higher identification rate than radioisotope alone (OR = 2.03, 95% CI 1.53-2.69, P < 0.05). However, no statistically significant difference was revealed for patients after neoadjuvant chemotherapy (OR = 1.64, 95% CI 0.82-3.27, P > 0.05), or for studies with high proportion of patients with positive lymphoscintigraphy (OR = 1.41, 95% CI 0.83-2.39, P > 0.05). Dual tracers did not significantly lower the false-negative rate compared with radioisotope alone (OR = 0.76, 95% CI 0.44-1.29, P > 0.05).Conclusions: Although the combination of blue dye and radioisotope outperformed radioisotope alone in SLN detection, the superiority for dual tracers may be limited for patients with positive lymphoscintigraphy or for those after neoadjuvant chemotherapy. Besides, the combined modality did not help lower the false-negative rate. [ABSTRACT FROM AUTHOR]

Background: This meta-analysis explored the efficacy and safety of anterior cervical corpectomy and fusion (ACCF) comparing to anterior cervical discectomy and fusion (ACDF) in treating cervical spondylotic myelopathy (CSM) patients. Methods: Several electronic databases were searched combined with manually searching. Thirteen randomized controlled studies were enrolled with 1,062 CSM patients, including 468 patients and 594 patients in the in the ACCF and ACDF group, respectively. The meta-analysis was then performed using the STATA 12.0 software. Crude standard mean difference (SMD) or odds ratio (OR) with their 95% confidence intervals (CI) were calculated. Results: Our meta-analysis results revealed that CSM patients in ACDF group showed less blood loss than those in ACCF group (SMD = 1.21, 95% CI = 1.03 ~ 1.39, P < 0.001). The operation time of CSM patients in the ACDF group was also obviously shorter than those in ACCF group (SMD = 0.40, 95% CI = 0.23 ~ 0.57, P < 0.001). Furthermore, CSM patients in ACDF group had shorter hospital time than those in ACCF group (SMD = 0.45, 95% CI = 0.21 ~ 0.69, P < 0.001). Conclusion: Our findings provide empirical evidence that ACDF may be more effective than ACCF for CSM treatment. [ABSTRACT FROM AUTHOR]

Abstract: Background: Although there is an inverse relationship between bone mass and marrow adiposity, the reversal function of zoledronic acid (ZOL) on increased marrow fat has not been studied. The aim of our study is to use the 3T magnetic resonance spectroscopy (MRS) to characterize the dynamical change process of the marrow fat responding to early ZOL treatment in the rabbit model with glucocorticoid-induced bone loss. Methods: Fifteen 20-week-old female New Zealand White rabbits were randomized to control group, methylprednisolone (MPS) group, and MPS+ZOL group equally. Bone mineral density (BMD) and marrow fat fraction (FF) at L3–L4 vertebrae and left proximal femur were measured by Dual-energy X-ray absorptiometry and MRS at week 0, 4, 8, and 12. The animals were euthanized at the end of our experiment and their left femurs were dissected out for the histopathological examination. Results: The MPS group demonstrated a remarkable increase in FF but a reduction in BMD compared with the controls at week 4 and 8, respectively (P <0.05 for all). Early treatment of ZOL can inhibit bone degeneration, although the bone mass would not recover to its original level. FF in MPS group exhibited a dramatic increase over time, with an increased FF variation (+31.6%, P =0.009) at week 4 from baseline and it was maintained until week 12 (+75.2%, P <0.001). In MPS+ZOL group, the FF returned to baseline value after the ZOL treatment. Comparing with the controls, larger marrow adipocyte density, the mean of the adipocyte diameter, and the percentage area of the adipocyte were observed in the MPS group (P <0.05 for all), whereas there were no significant differences in quantitative parameters of marrow adipocytes between the ZOL-treated group and the normal rabbits. Conclusion: An increase of the marrow adiposity is synchronized with the deterioration of the MPS-induced bone mass. A single dose of early ZOL can reverse the marrow adiposity to its original level completely. [Copyright &y& Elsevier]

Digested residues from biogas plants are often used as biofertilizers for agricultural crops cultivation. The antibiotic resistance genes (ARGs) in digested residues pose a high risk to public health due to their potential spread to the disease-causing microorganisms and thus reduce the susceptibility of disease-causing microorganisms to antibiotics in medical treatment. A high-throughput sequencing (HTS)-based metagenomic approach was used in the present study to investigate the variations of ARGs in full-scale biogas reactors and the correlations of ARGs with microbial communities and metal resistance genes (MRGs). The total abundance of ARGs in all the samples varied from 7 × 10-3 to 1.08 × 10-1 copy of ARG/copy of 16S-rRNA gene, and the samples obtained from thermophilic biogas reactors had a lower total abundance of ARGs, indicating the superiority of thermophilic anaerobic digestion for ARGs removal. ARGs in all the samples were composed of 175 ARG subtypes; however, only 7 ARG subtypes were shared by all the samples. Principal component analysis and canonical correspondence analysis clustered the samples into three groups (samples from manure-based mesophilic reactors, manure-based thermophilic reactors, and sludge-based mesophilic reactors), and substrate, temperature, and hydraulic retention time (HRT) as well as volatile fatty acids (VFAs) were identified as crucial environmental variables affecting the ARGs compositions. Procrustes analysis revealed microbial community composition was the determinant of ARGs composition in biogas reactors, and there was also a significant correlation between ARGs composition and MRGs composition. Network analysis further revealed the co-occurrence of ARGs with specific microorganisms and MRGs. [ABSTRACT FROM AUTHOR]

Abstract: The underlying causes of post-operative cognitive dysfunction (POCD) in elderly patients remain to be elucidated. In order to explore possible contributory mechanisms, we tested the effects of isoflurane anesthesia on (i) expression of hippocampal neuronal nitric oxide synthase (nNOS) and (ii) the relationship of changes in nNOS expression to cognitive dysfunction in isoflurane-treated aged rats. Our results indicate that isoflurane treatment leads to significant changes in correct reactions (F =28.35, p <0.001), initiative avoidances (F =29.33, p <0.001), and total reaction time (TRT) (F =6.99, p <0.05) of treated rats in the Y-maze test. Isoflurane-treated rats had fewer correct reactions and initiative avoidances in the Y-maze test 24 and 48h after 2h of isoflurane anesthesia compared with control group rats (p <0.05). TRTs to complete 20 trials of the Y-maze test increased significantly 48h after 2h anesthesia. The number of nNOS-positive hippocampal neurons decreased 24h after anesthesia, corresponding to an increased mean immunostaining grey-scale value. These data show that isoflurane causes a transient decrease in expression of hippocampal nNOS in aged rats during early post-anesthesia stages, and that the transient decrease of nNOS is closely correlated with cognitive impairment in isoflurane-treated aged rats. [Copyright &y& Elsevier]

The relevance of antiphospholipid (aPL), antinuclear (ANA) or antithyroid (ATA) antibodies in women undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) are controversial. The present study aims to investigate which autoantibodies are associated with the pregnancy outcome of patients undergoing first IVF/ICSI treatment. A total of 3763 IVF/ICSI patients were recruited from January to December 2015. Forty-five patients positive for aPL presenting adverse outcomes in their first cycle received low-dose aspirin treatment before the second transfer. Logistic regression analyses were performed to assess any association between autoantibodies and IVF/ICSI outcomes. The aCL-IgG was significantly associated with live birth rate (OR 0.58, 95% CI 0.36–0.96, p < 0.05) and miscarriage rate (OR 2.04, 95% CI 1.23–3.40, p < 0.01). The aCL-IgM was associated with miscarriage rate (OR 2.14, 95% CI 1.29–3.54, p < 0.01). The aβ 2 GPI-IgG was associated with implantation rate and clinical pregnancy rate (OR 0.61, 95% CI 0.24–0.96, p < 0.05; OR 0.40, 95% CI 0.13–0.87, p < 0.05, respectively). After the low-dose aspirin treatment, the live birth rate (37.0% vs. 19.1%, p < 0.05) increased significantly in patients with positive for aPL. In contrary, the aβ 2 GPI-IgM, ANA, anti-thyroglobulin (aTG) and anti-thyroperoxidase (aTPO) antibodies had no association with IVF/ICSI outcome. It is suggested that the presence of aCL-IgG, aCL-IgM and aβ 2 GPI-IgG might exert a detrimental effect on IVF/ICSI outcomes. Low-dose aspirin treatment could be useful for patients positive for these antibodies. Therefore, it is suggested that these antibodies should be assessed prior to IVF/ICSI treatment. [ABSTRACT FROM AUTHOR]

Aims: To investigate the relationship between serum phospholipid omega-3 polyunsaturated fatty acids (w-3 PUFAs) and insulin resistance (IR) in patients with type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). Methods: 51 patients with T2DM and NAFLD (T2DM + NAFLD group), 50 with T2DM alone (T2DM group), 45 with NAFLD alone (NAFLD group), and 42 healthy control subjects (NC group) were studied. Serum ω-3 PUFA profiles were analyzed by gas chromatography, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), and serum lipid concentrations were measured. Insulin resistance was assessed by the homeostasis model assessment method (HOMA-IR). Results: HOMA-IR levels were higher in the T2DM + NAFLD group than in the T2DM, NAFLD and NC groups (p < 0.05), as were ALT, AST, GGT, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) concentrations (p < 0.05). Conversely, serum ω-3 PUFA levels were significantly lower in the T2DM + NAFLD group than in the other groups (p < 0.05). The ω-3 PUFA level was negatively correlated with HOMA-IR, TC, LDL-C and TG. Conclusions: Serum phospholipid ω-3 PUFA levels were significantly decreased in patients with T2DM and NAFLD, and were negatively related with insulin resistance. Thus, reduced ω-3 PUFAs may play an important role in the development of T2DM and NAFLD. [ABSTRACT FROM AUTHOR]

Aim of the study: The aim of the present study was to evaluate the putative protective effect of 5-hydroxymethylfurfural (5-HMF) derived from processed Fructus Corni on human hepatocyte cell line (LO2) injured by hydrogen peroxide in vitro and the mechanism of its protection. Materials and methods: The percentage of cell viability was evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. The hepatocyte cell apoptosis and cell cycle were detected by flow cytometric analysis. The content of nitric oxide and caspase-3 activity were quantified spectrophotometrically by enzyme-linked immunoassay. Result: The study showed that incubation with 5-HMF caused significant increase in the viability of LO2 cell, decrease of cell apoptosis and recovery of cell cycle in LO2 cell injured by hydrogen peroxide, which was accompanied with the decreased nitric oxide level and caspase-3 activity. Conclusions: Our data suggest that 5-HMF protects LO2 cell against damage induced by hydrogen peroxide through inhibiting effect of cell apoptosis caused by promoting S phase to G2/M phase and the decreased caspase-3 activity and nitric oxide level. 5-HMF is one of the active principles in processed Fructus Corni. [Copyright &y& Elsevier]