The efficacy of neoadjuvant immunotherapy combined with chemotherapy in elderly patients with gastric cancer: A subgroup analysis of the NEOSUMMIT-01 study.

Based on a subanalysis of the NEOSUMMIT-01 study, it was revealed that perioperative immune checkpoint blockade (ICB) combined with chemotherapy has therapeutic effects in elderly patients with locally advanced gastric cancer, providing a new strategy for the treatment of elderly gastric cancer patients.

RAD51 High-Expressed Hepatocellular Carcinomas are Associated With High Cell Proliferation.

INTRODUCTION: RAD51 is a pivotal DNA repair gene managing double-stranded DNA break recognition and repair. RAD51 high expression was associated with adverse outcomes in other cancer types. This study aims to investigate the tumor microenvironment and immune landscape in the RAD51 high-expressed Hepatocellular Carcinoma (HCCs). METHODS: A total of 467 patients from two large independent cohorts with clinical and transcriptomic data were obtained. The cohort was dichotomized based on the median RAD51 gene expression. xCell and Gene Set Enrichment Analysis (GSEA) were used. RESULTS: RAD51 high-expressed HCCs were associated with worse recurrence-free, progression-free, disease-specific, and overall survival (all P < 0.05). While RAD51 high-expressed HCCs were associated with intratumoral heterogeneity, homologous recombination deficiency, and fraction altered scores, mutation or neoantigens were not increased in this group. xCell analysis demonstrated inconsistent immune cell infiltration between two cohorts. Cytolytic activity as well as GSEA with immune-related gene sets also demonstrated inconsistent results between two cohorts as well. On the other hand, RAD51 expression was significantly increased in higher-grade tumors, larger tumors, and higher clinical stages. RAD51 high-expressed HCCs were found to have elevated proliferation score. Furthermore, GSEA exhibited significant enrichment of all the cell proliferation-related gene sets in the Hallmark collection, including E2F targets, G2M checkpoint, Mitotic spindle, MYC targets, and MTORC1 signaling consistently in both cohorts (all false discovery rate < 0.25). CONCLUSIONS: RAD51 high-expressed HCCs were associated with worse survival and with increased cell proliferation and were not necessarily associated with immune infiltration or inflammation.

Analysis of D-dimer levels for the detection of deep venous thrombosis for patients with spinal metastasis undergoing decompression with fixation.

BACKGROUND: Deep venous thrombosis (DVT) after spinal surgery has recently attracted increasing attention. Patients with spinal metastases who undergo decompression with fixation are at a high risk of developing DVT. D-dimer levels indicate the risk of DVT, and the purpose of our study was to investigate D-dimer levels as a predictor of DVT perioperatively. METHODS: We prospectively evaluated 100 patients with spinal metastases. D-dimer tests were performed twice: once before surgery and one day postoperatively. DVT was diagnosed by duplex ultrasonographic assessment of both lower extremities. Pulmonary embolisms (PEs) were diagnosed using multidetector computed tomography and pulmonary angiography. Perioperative serum D-dimer levels were compared between the DVT (+) and DVT (-) groups. The cutoff value of the D-dimer level was calculated using receiver operating characteristic analysis. RESULTS: Preoperative and postoperative DVT prevalences were 8.0% (8/100) and 6.6% (6/91), respectively, and none of the patients developed PE. Before surgery, there was no significant differences in D-dimer levels between the pre-DVT (+) and pre-DVT (-) groups. After surgery, the D-dimer level one-day postoperatively for the post-DVT (+) group (17.6 ± 11.8 mg/L) was significantly higher than that of the post-DVT (-) group (5.0 ± 4.7 mg/L). The cutoff value of the postoperative D-dimer level was 9.51(mg/L), and the sensitivity and specificity for the optimum threshold were 83.3% and 89.4%, respectively. CONCLUSIONS: Our findings suggest that preoperative D-dimer level may not be a predictor of DVT. Preoperative ultrasound examinations should be routinely performed in patients with spinal metastases. Postoperative D-dimer levels greater than 9.51(mg/L) are a predictive factor for the early diagnosis of DVT after spine surgery. TRIAL REGISTRATION: Our study was registered on Chinese Clinical Trial Registry (No.ChiCTR2000029737). Registered 11 February 2020 - Retrospectively registered, https://www.chictr.org.cn/index.aspx.

Overexpression of COX7A1 Promotes the Resistance of Gastric Cancer to Oxaliplatin and Weakens the Efficacy of Immunotherapy.

Gastric cancer (GC) is one of the most common clinical malignant tumors worldwide, with high morbidity and mortality. Presently, the overall response rate to immunotherapy is low, and current methods for predicting the prognosis of GC are not optimal. Therefore, novel biomarkers with accuracy, efficiency, stability, performance ratio, and wide clinical application are needed. Based on public data sets, the chemotherapy cohort and immunotherapy cohort from Sun Yat-sen University Cancer Center, a series of bioinformatics analyses, such as differential expression analysis, survival analysis, drug sensitivity prediction, enrichment analysis, tumor immune dysfunction and exclusion analysis, single-sample gene set enrichment analysis, stemness index calculation, and immune cell infiltration analysis, were performed for screening and preliminary exploration. Immunohistochemical staining and in vitro experiments were performed for further verification. Overexpression of COX7A1 promoted the resistance of GC cells to Oxaliplatin. COX7A1 may induce immune escape by regulating the number of fibroblasts and their cellular communication with immune cells. In summary, measuring the expression levels of COX7A1 in the clinic may be useful in predicting the prognosis of GC patients, the degree of chemotherapy resistance, and the efficacy of immunotherapy.

Higher inflammatory response in hepatocellular carcinoma is associated with immune cell infiltration and a better outcome.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) often develops from chronic liver inflammation. Inflammation within a tumor can either promote cancer progression or activate an immune response against it. This study aims to determine the clinical significance of enhanced inflammation in HCC. METHODS: Data from 655 HCC patients across four cohorts (TCGA, GSE6764, GSE76427, GSE89377) were examined. Inflammatory response was quantified using a scoring system derived from the gene set variation analysis of the "INFLAMMATORY_RESPONSE" gene set. RESULTS: A stepwise increase in inflammatory response was noted from normal liver to cirrhosis, with consistently lower levels in HCC across both GSE6764 and GSE89377 cohorts (both p < 0.001). Similar trends were observed in interferon response, pathways such as IL6/JAK/STAT3 and complement signaling, coagulation cascade, and allograft rejection (all p < 0.02). HCCs with high inflammatory response were associated with increased immune cell infiltrations (p < 0.01) and cytolytic activity (p < 0.001). Interestingly, these HCCs had reduced mutation rates, no relationship with cell proliferation, and displayed both immune responses and pro-cancerous signals including epithelial-mesenchymal transition, KRAS, and hypoxia. Further, a high inflammatory score correlated with improved disease-free survival in TCGA (p = 0.034) and overall survival in GSE76427 (p = 0.008). CONCLUSION: HCC with higher levels of inflammatory response demonstrated increased immune cell infiltration, enhanced immune-related and other pro-cancerous-related signaling, and showed a trend toward a better patient prognosis.

Source localization comparison and combination of OPM-MEG and fMRI to detect sensorimotor cortex responses.

BACKGROUND AND OBJECTIVES: The exploration of various neuroimaging techniques have become focal points within the field of neuroscience research. Magnetoencephalography based on optically pumped magnetometers (OPM-MEG) has shown significant potential to be the next generation of functional neuroimaging with the advantages of high signal intensity and flexible sensor arrangement. In this study, we constructed a 31-channel OPM-MEG system and performed a preliminary comparison of the temporal and spatial relationship between magnetic responses measured by OPM-MEG and blood-oxygen-level-dependent signals detected by functional magnetic resonance imaging (fMRI) during a grasping task. METHODS: For OPM-MEG, the ß-band (15-30 Hz) oscillatory activities can be reliably detected across multiple subjects and multiple session runs. To effectively localize the inhibitory oscillatory activities, a source power-spectrum ratio-based imaging method was proposed. This approach was compared with conventional source imaging methods, such as minimum norm-type and beamformer methods, and was applied in OPM-MEG source analysis. Subsequently, the spatial and temporal responses at the source-level between OPM-MEG and fMRI were analyzed. RESULTS: The effectiveness of the proposed method was confirmed through simulations compared to benchmark methods. Our demonstration revealed an average spatial separation of 10.57 ± 4.41 mm between the localization results of OPM-MEG and fMRI across four subjects. Furthermore, the fMRI-constrained OPM-MEG localization results indicated a more focused imaging extent. CONCLUSIONS: Taken together, the performance exhibited by OPM-MEG positions it as a potential instrument for functional surgery assessment.

Exploration of signature based on T cell-related genes in stomach adenocarcinoma by analysis of single cell sequencing data.

BACKGROUND: Gastric cancer (GC) is a leading reason for the death of cancer around the world. The immune microenvironment counts a great deal in immunotherapy of advanced tumors, in which T cells exert an indispensable function. METHODS: Single-cell RNA sequencing data were utilized to characterize the expression profile of T cells, followed by T cell-related genes (TCRGs) to construct signature and measure differences in survival time, enrichment pathways, somatic mutation status, immune status, and immunotherapy between groups. RESULTS: The complex tumor microenvironment was analyzed by scRNA-seq data of GC patients. We screened for these T cell signature expression genes and the TCRGs-based signature was successfully constructed and relied on the riskscore grouping. In gene set enrichment analysis, it was shown that pro-tumor and suppressive immune pathways were more abundant in the higher risk group. We also found different infiltration of immune cells in two groups, and that the higher risk samples had a poorer response to immunotherapy. CONCLUSION: Our study established a prognostic model, in which different groups had different prognosis, immune status, and enriched features. These results have provided additional insights into prognostic evaluation and the development of highly potent immunotherapies in GC.

Construction of a gene model related to the prognosis of patients with gastric cancer receiving immunotherapy and exploration of COX7A1 gene function.

BACKGROUND: GC is a highly heterogeneous tumor with different responses to immunotherapy, and the positive response depends on the unique interaction between the tumor and the tumor microenvironment (TME). However, the currently available methods for prognostic prediction are not satisfactory. Therefore, this study aims to construct a novel model that integrates relevant gene sets to predict the clinical efficacy of immunotherapy and the prognosis of GC patients based on machine learning. METHODS: Seven GC datasets were collected from the Gene Expression Omnibus (GEO) database, The Cancer Genome Atlas (TCGA) database and literature sources. Based on the immunotherapy cohort, we first obtained a list of immunotherapy related genes through differential expression analysis. Then, Cox regression analysis was applied to divide these genes with prognostic significancy into protective and risky types. Then, the Single Sample Gene Set Enrichment Analysis (ssGSEA) algorithm was used to score the two categories of gene sets separately, and the scores differences between the two gene sets were used as the basis for constructing the prognostic model. Subsequently, Weighted Correlation Network Analysis (WGCNA) and Cytoscape were applied to further screen the gene sets of the constructed model, and finally COX7A1 was selected for the exploration and prediction of the relationship between the clinical efficacy of immunotherapy for GC. The correlation between COX7A1 and immune cell infiltration, drug sensitivity scoring, and immunohistochemical staining were performed to initially understand the potential role of COX7A1 in the development and progression of GC. Finally, the differential expression of COX7A1 was verified in those GC patients receiving immunotherapy. RESULTS: First, 47 protective genes and 408 risky genes were obtained, and the ssGSEA algorithm was applied for model construction, showing good prognostic discrimination ability. In addition, the patients with high model scores showed higher TMB and MSI levels, and lower tumor heterogeneity scores. Then, it is found that the COX7A1 expressions in GC tissues were significantly lower than those in their corresponding paracancerous tissues. Meanwhile, the patients with high COX7A1 expression showed higher probability of cancer invasion, worse clinical efficacy of immunotherapy, worse overall survival (OS) and worse disease-free survival (DFS). CONCLUSIONS: The ssGSEA score we constructed can serve as a biomarker for GC patients and provide important guidance for individualized treatment. In addition, the COX7A1 gene can accurately distinguish the prognosis of GC patients and predict the clinical efficacy of immunotherapy for GC patients.

Gastric cancer with enhanced myogenesis is associated with less cell proliferation, enriched epithelial-to-mesenchymal transition and angiogenesis, and poor clinical outcomes.

Gastric cancer (GC) remains a lethal disease, with over 26,000 new cases and more than 11,000 deaths annually in the US. Thus, a deeper understanding of GC biology is critical to improve survival. Myogenesis is the formation of muscle fibers, which is a mesodermal tissue. In cancer, epithelial-to-mesenchymal transition (EMT) is a known phenomenon that promotes metastasis and poor survival. Given that myogenesis produces mesenchymal cells, we hypothesized that GC with increased myogenesis is linked to aggressive tumor behaviors and less favorable outcomes. In this study, three GC patient cohorts: TCGA (n=375), GSE26253 (n=432), and GSE84437 (n=482), were analyzed. The "MYOGENESIS" set in the Hallmark collection which comprises 200 myogenesis-related genes was analyzed to perform gene set variation analysis to create a score to quantify the myogenesis activity. Our results showed that T category of AJCC cancer staging that reflects the tumor invasion to stomach wall consistently correlated with myogenesis activity in two GC cohorts. High myogenesis GC was associated with lower cell proliferation, evidenced by reduced proliferation scores, decreased Ki67 gene expression, and less enrichment of E2F Targets, G2M checkpoint, MYC Targets V1, and V2 gene sets. High myogenesis tumors showed increased stromal cells (fibroblasts and adipocytes) infiltration within the tumor microenvironment, as well as less silent and non-silent mutation rates and copy number alterations. Higher lymphocyte infiltration, leukocyte fraction, T-cell receptor richness, and B-cell receptor richness were associated with high myogenesis GC. However, infiltration of CD4 cells, T helper type 1 and 2 cells, Natural Killer cells, regulatory T cells, and plasma cells was lower, with increased infiltration of dendritic cells in high myogenesis GC. High myogenesis GC enriched EMT, Hedgehog, TGF-ß, and KRAS gene sets. Furthermore, it was associated with enhanced angiogenesis, evidenced by enrichment of Angiogenesis, Coagulation, and Hypoxia gene sets, and increased infiltration of microvascular and lymphatic endothelial cells and pericytes. High myogenesis GC consistently correlated with worse overall survival in all three cohorts, and worse disease-specific and progression-free survival in the TCGA cohort. Hence, our findings suggest that GC with enhanced myogenesis is associated with decreased cell proliferation, increased EMT and angiogenesis, and worse prognosis.

Higher Inflammatory Response in Hepatocellular Carcinoma is Associated with Immune Cell Infiltration and a Better Outcome.

Background & Aims: Hepatocellular carcinoma (HCC) often develops from chronic liver inflammation. Inflammation within a tumor can either promote cancer progression or activate an immune response against it. This study aims to determine the clinical significance of enhanced inflammation in HCC. Methods: Data from 655 HCC patients across four cohorts (TCGA, GSE6764, GSE76427, GSE89377) were examined. Inflammatory response was quantified using a scoring system derived from the gene set variation analysis of the "INFLAMMATORY_RESPONSE" gene set. Results: A stepwise increase in inflammatory response was noted from normal liver to cirrhosis, with consistently lower levels in HCC across both GSE6764 and GSE89377 cohorts (both p<0.001). Similar trends were observed in interferon response, pathways such as IL6/JAK/STAT3 and complement signaling, coagulation cascade, and allograft rejection (all p<0.02). HCCs with high inflammatory response were associated with increased immune cell infiltrations (p<0.01) and cytolytic activity (p<0.001). Interestingly, these HCCs had reduced mutation rates, no relationship with cell proliferation, and displayed both immune responses and pro-cancerous signals including epithelial-mesenchymal transition, KRAS, and hypoxia. Further, a high inflammatory score correlated with improved disease-free survival in TCGA (p=0.034) and overall survival in GSE76427 (p=0.008). Conclusion: HCC with higher levels of inflammatory response demonstrated increased immune cell infiltration, enhanced immune-related and other pro-cancerous-related signaling, and better patient prognosis.

Inflammatory factors and risk of meningiomas: a bidirectional mendelian-randomization study.

Background: Meningiomas are one of the most common intracranial tumors, and the current understanding of meningioma pathology is still incomplete. Inflammatory factors play an important role in the pathophysiology of meningioma, but the causal relationship between inflammatory factors and meningioma is still unclear. Method: Mendelian randomization (MR) is an effective statistical method for reducing bias based on whole genome sequencing data. It's a simple but powerful framework, that uses genetics to study aspects of human biology. Modern methods of MR make the process more robust by exploiting the many genetic variants that may exist for a given hypothesis. In this paper, MR is applied to understand the causal relationship between exposure and disease outcome. Results: This research presents a comprehensive MR study to study the association of genetic inflammatory cytokines with meningioma. Based on the results of our MR analysis, which examines 41 cytokines in the largest GWAS datasets available, we were able to draw the relatively more reliable conclusion that elevated levels of circulating TNF-ß, CXCL1, and lower levels of IL-9 were suggestive associated with a higher risk of meningioma. Moreover, Meningiomas could cause lower levels of interleukin-16 and higher levels of CXCL10 in the blood. Conclusion: These findings suggest that TNF-ß, CXCL1, and IL-9 play an important role in the development of meningiomas. Meningiomas also affect the expression of cytokines such as IL-16 and CXCL10. Further studies are needed to determine whether these biomarkers can be used to prevent or treat meningiomas.

Construction and validation of a prognostic prediction model for gastric cancer using a series of genes related to lactate metabolism.

Background: Gastric cancer (GC) is one of the most common clinical malignant tumors worldwide, with high morbidity and mortality. The commonly used tumor-node-metastasis (TNM) staging and some common biomarkers have a certain value in predicting the prognosis of GC patients, but they gradually fail to meet the clinical demands. Therefore, we aim to construct a prognostic prediction model for GC patients. Methods: A total of 350 cases were included in the STAD (Stomach adenocarcinoma) entire cohort of TCGA (The Cancer Genome Atlas), including the STAD training cohort of TCGA (n = 176) and the STAD testing cohort of TCGA (n = 174). GSE15459 (n = 191), and GSE62254 (n = 300) were for external validation. Results: Through differential expression analysis and univariate Cox regression analysis in the STAD training cohort of TCGA, we screened out five genes among 600 genes related to lactate metabolism for the construction of our prognostic prediction model. The internal and external validations showed the same result, that is, patients with higher risk score were associated with poor prognosis (all p < 0.05), and our model works well without regard of patients' age, gender, tumor grade, clinical stage or TNM stage, which supports the availability, validity and stability of our model. Gene function analysis, tumor-infiltrating immune cells analysis, tumor microenvironment analysis and clinical treatment exploration were performed to improve the practicability of the model, and hope to provide a new basis for more in-depth study of the molecular mechanism for GC and for clinicians to formulate more reasonable and individualized treatment plans. Conclusions: We screened out and used five genes related to lactate metabolism to develop a prognostic prediction model for GC patients. The prediction performance of the model is confirmed by a series of bioinformatics and statistical analysis.

Metabolic regulation and antihyperglycemic properties of diet-derived PGG through transcriptomic and metabolomic profiling.

Diabetes has become a significant disease threatening human health and social development. Food intervention is considered an essential strategy to prevent early diabetes development sustainably. The natural product, 1,2,3,4,6-penta-O-galloyl-ß-D-glucose (PGG), commonly found in fruits and diets, has many potential antihypoglycemic, antibacterial, and antitumor activities. We found that PGG can promote glucose uptake in whole-organism zebrafish screening, which help in downregulating the glucose levels. We investigated the metabolome and transcriptome changes in zebrafish exposed to high glucose and PGG intervention. The differential genes and metabolites were screened out based on the comparisons of blank, hyperglycemic, and the PGG-exposed groups of zebrafish larvae. Combined with RT-qPCR validation, we found that PGG mainly restored four genes (fthl27, LOC110438965, plat, and aacs) and six metabolites abnormally invoked by high glucose. These validated genes are related with the key metabolites sphingosine and (R)-3-hydroxybutanoate involving the pathways of apelin, apoptosis, necroptosis, and butanoate metabolism. Our findings provided a new mechanistic basis for understanding the hypoglycaemic function of the commonly present dietary molecule (PGG) and offered a new perspective for the rational utilization of PGG to regulate metabolic disorders.

Amygdalin alleviated TGF-ß-induced epithelial-mesenchymal transition in bronchial epithelial cells.

OBJECTIVE: Transforming growth factor-beta TGF-ß-induced epithelial-mesenchymal transition (EMT) in bronchial epithelial cells contributes to airway wall remodeling in asthma. This study aims to explore the role of amygdalin, an active ingredient in bitter almonds, in TGF-ß-induced EMT in bronchial epithelial cells and to elucidate the possible mechanisms underlying its biological effects. METHODS: An asthmatic mouse model was established through ovalbumin induction. Primary mouse bronchial epithelial cells and a human bronchial epithelial cell line were incubated with transforming growth factor-beta (TGF-ß) to induce EMT, whose phenotype of cells was evaluated by the expressions of EMT markers [alpha-smooth muscle actin (α-SMA), vimentin, and fibronectin] and cell migration capacity. A co-immunoprecipitation assay was performed to assess the ubiquitination of heparanase (HPSE). RESULTS: In asthmatic model mice, amygdalin treatment relieved airway wall remodeling and decreased expressions of EMT markers (α-SMA and vimentin). In TGF-ß-treated bronchial epithelial cells, amygdalin treatment decreased the mRNA and protein levels of EMT markers (α-SMA, vimentin, and fibronectin) without impairing cell viability. Through the Swiss Target Prediction database, HPSE was screened as a candidate downstream target for amygdalin. HPSE overexpression further promoted TGF-ß-induced EMT while the HPSE inhibitor suppressed TGF-ß-induced EMT in bronchial epithelial cells. In addition, HPSE overexpression reversed the inhibitory effect of amygdalin on TGF-ß-induced EMT in bronchial epithelial cells. The following mechanism exploration revealed that amygdalin downregulated HPSE expression by enhancing ubiquitination. CONCLUSION: Our study showed that amygdalin inhibited TGF-ß-induced EMT in bronchial epithelial cells and found that the anti-EMT activity of amygdalin might be related to its regulatory effect on HPSE expression.

Effects of hot-air microwave rolling blanching pretreatment on the drying of turmeric (Curcuma longa L.): Physiochemical properties and microstructure evaluation.

Blanching pretreatment can improve product quality and efficiency during food processing. Effects of hot-air microwave rolling blanching (HMRB) on physiochemical properties and microstructure of turmeric were investigated under various treatment times (0-10 min). Results showed that HMRB significantly changed weight, electrolyte leakage, texture, viscoelastic properties, pectin fractions content, thermal properties and drying quality of turmeric. Meanwhile, HMRB promoted the redistribution of water in turmeric and changed the cell structure, thus shortening drying time by 6.35-34.92 %. The polyphenol oxidase and peroxidase were entirely inactivated after blanching for 8 and 10 min, respectively. Compared with unblanched dried turmeric, the curcumin content, total phenolic, DPPH and ABTS were significantly increased by 20.76 %, 5.63 %, 7.54 % and 19.05 % at the optimal blanching time (8 min). Overall, HMRB can be used as a promising pretreatment technology to enhance the drying rate and improve the quality of dried turmeric.

SLC1A1-mediated cellular and mitochondrial influx of R-2-hydroxyglutarate in vascular endothelial cells promotes tumor angiogenesis in IDH1-mutant solid tumors.

Mutant isocitrate dehydrogenase 1 (mIDH1) drives tumorigenesis via producing oncometabolite R-2-hydroxyglutarate (R-2-HG) across various tumor types. However, mIDH1 inhibitors appear only effective in hematological tumors. The therapeutic benefit in solid tumors remains elusive, likely due to the complex tumor microenvironment. In this study, we discover that R-2-HG produced by IDH1-mutant tumor cells is preferentially imported into vascular endothelial cells and remodels mitochondrial respiration to promote tumor angiogenesis, conferring a therapeutic vulnerability in IDH1-mutant solid tumors. Mechanistically, SLC1A1, a Na+-dependent glutamate transporter that is preferentially expressed in endothelial cells, facilitates the influx of R-2-HG from the tumor microenvironment into the endothelial cells as well as the intracellular trafficking of R-2-HG from cytoplasm to mitochondria. R-2-HG hijacks SLC1A1 to promote mitochondrial Na+/Ca2+ exchange, which activates the mitochondrial respiratory chain and fuels vascular endothelial cell migration in tumor angiogenesis. SLC1A1 deficiency in mice abolishes mIDH1-promoted tumor angiogenesis as well as the therapeutic benefit of mIDH1 inhibitor in solid tumors. Moreover, we report that HH2301, a newly discovered mIDH1 inhibitor, shows promising efficacy in treating IDH1-mutant cholangiocarcinoma in preclinical models. Together, we identify a new role of SLC1A1 as a gatekeeper of R-2-HG-mediated crosstalk between IDH1-mutant tumor cells and vascular endothelial cells, and demonstrate the therapeutic potential of mIDH1 inhibitors in treating IDH1-mutant solid tumors via disrupting R-2-HG-promoted tumor angiogenesis.

CX3CL1 in the red bone marrow promotes renal cell carcinoma to metastasize to the spine by involving the Src-related pathway.

Spinal metastasis (SM) frequently occurs in renal cell carcinoma (RCC) patients. Our preliminary work showed that CX3CL1 plays a positive role in SM. The objective of the present study was to verify whether CX3CL1 activates the downstream pathway by binding to CX3CR1 in RCC cells, ultimately promoting RCC to metastasize to the spine. The expression of CX3CL1 and CX3CR1 in tissue samples was detected by immunohistochemistry and western blotting. ELISA was used to quantify the concentration of CX3CL1 in the serum. The expression level of CX3CR1 in RCC cell lines was also detected. The CellTiter-Glo assay and flow cytometry were used to analyze cell viability and apoptosis of RCC cells. Transwell and wound healing assay were used to analyze the effect of CX3CL1 on the invasion and migration ability of RCC cells. Specific inhibitors were used to interfere with key molecules in the signaling pathway to further explore the signal transduction in RCC cells after CX3CL1 stimulation. The expression of CX3CR1 in SM from RCC was higher than that in limb bone metastases. Among the five RCC cell lines, 786O cells expressed the highest level of CX3CR1. CX3CL1 neither inhibited the proliferation of 786O cells nor promoted the apoptosis of 786O cells. However, it promoted the migration and invasion of RCC cells. After CX3CL1 stimulation, Src and Focal adhesion kinase (FAK) phosphorylation levels increased in RCC cells. Bosutinib and PF-00562271 inhibited Src/FAK phosphorylation and cell motility and invasion triggered by CX3CL1 stimulation. CX3CL1 in the red bone marrow of spinal cancellous bone enhances migration and invasion abilities of RCC cells, thereby promoting RCC metastasize to the spine. The migration and invasion of RCC cells activated by CX3CL1 are at least partially dependent on Src/FAK activation.

Hot-Air Flow Rolling Dry-Blanching Pretreatment Improves the Drying Quality of Acanthopanax sessiliflorus by Increasing the Drying Rate and Inactivating Enzymes.

The processing of Acanthopanax sessiliflorus has attracted interest due to its health benefits. In this work, an emerging blanching technology, called hot-air flow rolling dry-blanching (HMRDB), was employed to treat A. sessiliflorus before drying. The effects of varied blanching times (2-8 min) on enzyme inactivation, drying characteristics, bioactive compound retention, and microstructure were examined. The results demonstrated that blanching for 8 min rendered polyphenol oxidase and peroxidase nearly inactive. The blanching process reduced the drying time of samples by up to 57.89% compared to an unblanched sample. The Logarithmic model showed good fitting performance for the drying curves. The total phenolic and flavonoid content of the dried product increased as blanching time increased. The total anthocyanin content of the samples blanched for 6 min was 3.9 times higher than that of the unblanched samples, and 8 min of blanching produced the greatest DPPH• and ABTS• scavenging capabilities. The retention of active compounds in a dried product is a result of the inactivation of enzymes and a reduced drying period. Changes in the porous structure of the blanched samples would be responsible for the accelerated drying rate, according to microstructural analysis. These results indicate that HMRDB enhances the drying process and improves drying quality when applied to A. sessiliflorus before drying.

Effect of different drying techniques on drying kinetics, nutritional components, antioxidant capacity, physical properties and microstructure of edamame.

The present study aimed to investigate the effect of hot air drying (HD), microwave rolling-bed drying (MRD), hot air microwave rolling-bed drying (HMRD), pulse-spouted microwave vacuum drying (PSMVD) and freeze-drying (FD) on the drying characteristics, quality properties and microstructure of edamame. Six models were fitted the drying curves, and quality attributes were analyzed. Results indicated that Page model was the most suited model for edamame drying. Compared with HD, MRD and HMRD improved the quality of edamame and decreased the drying time by 45.59% and 36.03% respectively. The FD and PSMVD possessed higher rehydration ability, nutrient retention and antioxidant capacity compared with other methods. Moreover, PSMVD products showed a crunchy texture, the less color change and the shortest drying time (70 min). Microscopy images demonstrated a distinct porous structure in PSMVD, which facilitated the moisture transfer. Overall, PSMVD is a promising dehydration method for obtaining high value-added edamame products.

The Clinical Effect of a Combination of Mouse Nerve Growth Factor and Methylcobalamin to Treat Lumbar Disc Herniation with Foot Drop: A Retrospective Cohort Study.

OBJECTIVE: To investigate the clinical effect of mouse nerve growth factor (mNGF) and methylcobalamin (MeCbl) for the treatment of lumbar disk herniation (LDH) with foot drop. METHODS: A total of 46 patients suffering from LDH with foot drop who underwent transforaminal lumbar interbody fusion (TLIF) surgery in our department from January 2015 to December 2017 were retrospectively analyzed. We divided these patients into two groups according to the different postoperative treatment which independently selected by patients after signing informed consent form: one group of 25 patients was treated with MeCbl alone (Group MeCbl), the other group of 21 patients was treated with a combination of mNGF and MeCbl (Group MeCbl+mNGF). Patient demographics, the visual analogue scale (VAS) scores, sensory and muscular strength improvement statistics at 1 week, 4 weeks, 12 weeks, and 12 months postoperatively were recorded. Motor/sensory deficits, sciatica and overall neurological outcome after treatment of MeCbl alone and combination of mNGF and MeCbl were retrospectively analyzed. RESULTS: The follow-up ranged between 12 and 42 months (mean 20.8 months). There were no significant differences between these two groups of patients with respect to sex ratio, age, smoking, diabetes, disease course, section of protruding disc(s), muscular strength of foot dorsiflexion or preoperative visual analogue scale (VAS) score (P > 0.05). The VAS scores of Group MeCbl+mNGF were significantly lower than Group MeCbl at 1 week, 4 weeks, 12 weeks, and 12 months postoperatively (4.32 ± 0.75 vs 5.25 ± 0.79,2.65 ± 0.48 vs 3.42 ± 0.52, 1.72 ± 0.36 vs 2.45 ± 0.39, 1.12 ± 0.22 vs 1.52 ± 0.24, P < 0.05). The effective rates of sensory improvement were significantly higher in Group MeCbl+mNGF compared with Group MeCbl at 12-week/12-month follow-up time point (90.48% vs 52.00%,95.24% vs 68.00%, P < 0.05). The effective rate of muscular strength improvement of the two groups did not differ significantly at 1 week after surgery but exhibited statistically significant differences at subsequent time points (61.90% vs 32.00%, 76.19% vs 44.00%, 80.95% vs 48.00%, P < 0.05). CONCLUSIONS: Application of mNGF had clinical effects on promoting the recovery of neurological function in patients suffering from LDH with foot drop.