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Background: Abnormal levels of glutamate constitute a key pathophysiologic mechanism in epilepsy. The use of glutamate chemical exchange saturation transfer (GluCEST) imaging to measure glutamate levels in pediatric epilepsy is rarely reported in research., Purpose: To investigate hippocampal glutamate level variations in pediatric epilepsy and the correlation between glutamate and hippocampal subregional volumes., Study Type: Cross-sectional, prospective., Subjects: A total of 38 school-aged pediatric epilepsy patients with structurally normal MRI as determined by at least two independent radiologists (60% males; 8.7 ± 2.5 years; including 20 cases of focal pediatric epilepsy [FE] and 18 cases of generalized pediatric epilepsy [GE]) and 17 healthy controls (HC) (41% males; 9.0 ± 2.5 years)., Field Strength/sequence: 3.0 T; 3D magnetization prepared rapid gradient echo (MPRAGE) and 2D turbo spin echo GluCEST sequences., Assessment: The relative concentration of glutamate was calculated through pixel-wise magnetization transfer ratio asymmetry (MTR asym ) analysis of the GluCEST data. Hippocampal subfield volumes were computed from MPRAGE data using FreeSurfer., Statistical Tests: This study used t tests, one-way analysis of variance, Kruskal-Wallis tests, and Pearson correlation analysis. P < 0.05 was considered statistically significant., Results: The MTR asym values of both the left and right hippocampi were significantly elevated in GE (left: 2.51 ± 0.23 [GE] vs. 2.31 ± 0.12 [HCs], right: 2.50 ± 0.22 [GE] vs. 2.27 ± 0.22 [HCs]). The MTR asym values of the ipsilateral hippocampus were significantly elevated in FE (2.49 ± 0.28 [ipsilateral] vs. 2.29 ± 0.16 [HCs]). The MTR asym values of the ipsilateral hippocampus were significantly increased compared to the contralateral hippocampus in FE (2.49 ± 0.28 [ipsilateral] vs. 2.35 ± 0.34 [contralateral]). No significant differences in hippocampal volume were found between different groups (left hippocampus, P = 0.87; right hippocampus, P = 0.87)., Data Conclusion: GluCEST imaging have potential for the noninvasive measurement of glutamate levels in the brains of children with epilepsy., Level of Evidence: 2 TECHNICAL EFFICACY: Stage 1., (© 2024 International Society for Magnetic Resonance in Medicine.)

Intestinal stem cells differentiate into absorptive enterocytes, characterised by increased brush border enzymes such as intestinal alkaline phosphatase (IAP), making up the majority (95%) of the terminally differentiated cells in the villus. Loss of integrity of the intestinal epithelium plays a key role in inflammatory diseases and gastrointestinal infection. Here, we show that the intestinal microRNA (miR)-27a-3p is an important regulator of intestinal epithelial cell proliferation and enterocyte differentiation. Repression of endogenous miR-27a-3p leads to increased enterocyte differentiation and decreased intestinal epithelial cell proliferation in mouse and human small intestinal organoids. Mechanistically, miR-27a-3p regulates intestinal cell differentiation and proliferation at least in part through the regulation of retinoic acid receptor α (RXRα), a modulator of Wnt/β-catenin signalling. Repression of miR-27a-3p increases the expression of RXRα and concomitantly, decreases the expression of active β-catenin and cyclin D1. In contrast, overexpression of miR-27a-3p mimic decreases the expression of RXRα and increases the expression of active β-catenin and cyclin D1. Moreover, overexpression of the miR-27a-3p mimic results in impaired enterocyte differentiation and increases intestinal epithelial cell proliferation. These alterations were attenuated or blocked by Wnt inhibition. Our study demonstrates an miR-27a-3p/RXRα/Wnt/β-catenin pathway that is important for the maintenance of enterocyte homeostasis in the small intestine., (© 2024 The Author(s). Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)

Our previous study has reported that metastasis-associated protein 2 ( MTA2 ) plays essential roles in tumorigenesis and aggressiveness of gastric cancer (GC). However, the underlying molecular mechanisms of MTA2 -mediated GC and its upstream regulation mechanism remain elusive. In this study, we identified a novel circular RNA (circRNA) generated from the MTA2 gene (circ MTA2 ) as a crucial regulator in GC progression. Circ MTA2 was highly expressed in GC tissues and cell lines, and circ MTA2 promoted the proliferation, invasion, and metastasis of GC cells both in vitro and in vivo. Mechanistically, circ MTA2 interacted with ubiquitin carboxyl-terminal hydrolase L3 (UCHL3) to restrain MTA2 ubiquitination and stabilize MTA2 protein expression, thereby facilitating tumor progression. Moreover, circ MTA2 was mainly encapsulated and transported by exosomes to promote GC cell progression. Taken together, these findings uncover that circ MTA2 suppresses MTA2 degradation by interacting with UCHL3, thereby promoting GC progression. In conclusion, we identified a cancer-promoting axis (circ MTA2 /UCHL3/ MTA2 ) in GC progression, which paves the way for us to design and synthesize targeted inhibitors as well as combination therapies.

Background: Traumatic brain injury (TBI) often leads to cognitive and neurological dysfunction. Valproic acid (VPA) has a neuroprotective effect in acute central nervous system diseases; the neurotrophin 3 gene (NT-3) can maintain the survival of neurons, and olfactory ensheathing cells (OECs) can promote the growth of nerve axons. This study aimed to evaluate the restorative effect of VPA combined with NT-3 modified OECs (NT-3-OECs) on neurological function after TBI., Methods: The neurological severity score (NSS) of rats was evaluated on the 1st, 7th, 14th, and 28th day after TBI modeling and corresponding intervention. Hematoxylin-eosin (HE) staining, p75 nerve growth factor receptor (P75), glial fibrillary acidic protein (GFAP), and neurofilament protein (NF)staining, and argyrophilic staining were used to observe the morphology of brain tissue 28 days after modeling. Moreover, TdT-mediated dUTP Nick-End Labeling (TUNEL) was used to detect the apoptosis rate of neurons. The changes in synapses and mitochondria in the injured area were observed by electron microscope., Results: NT-3-OECs transplantation can increase the content of NT-3 in brain tissue, and NT-3-OECs can survive for >28 days. The NSS score of the TBI-VPA-NT-3-OECs group 28 days after cell transplantation was significantly lower than that of the other model treatment groups (P < 0.05). The morphological structure of the brain tissue was more complete, and the neurofilament fibers were neatly arranged, achieving better results than those of the other groups. The apoptosis rate of nerve cells in the TBI-VPA-NT-3-OECs group was significantly lower than in the other treatment groups (P < 0.05). Furthermore, the number of synapses in the combined intervention group was significantly higher than in the other treatment groups, and the mitochondrial structure was more complete., Conclusion: NT-3-OECs have good biological function, and VPA combined with NT-3-OECs transplantation can effectively improve the prognosis of TBI rats., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest pertaining to this research., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Ferroptosis, a regulated form of cellular death characterized by the iron-mediated accumulation of lipid peroxides, provides a novel avenue for delving into the intersection of cellular metabolism, oxidative stress, and disease pathology. We have witnessed a mounting fascination with ferroptosis, attributed to its pivotal roles across diverse physiological and pathological conditions including developmental processes, metabolic dynamics, oncogenic pathways, neurodegenerative cascades, and traumatic tissue injuries. By unraveling the intricate underpinnings of the molecular machinery, pivotal contributors, intricate signaling conduits, and regulatory networks governing ferroptosis, researchers aim to bridge the gap between the intricacies of this unique mode of cellular death and its multifaceted implications for health and disease. In light of the rapidly advancing landscape of ferroptosis research, we present a comprehensive review aiming at the extensive implications of ferroptosis in the origins and progress of human diseases. This review concludes with a careful analysis of potential treatment approaches carefully designed to either inhibit or promote ferroptosis. Additionally, we have succinctly summarized the potential therapeutic targets and compounds that hold promise in targeting ferroptosis within various diseases. This pivotal facet underscores the burgeoning possibilities for manipulating ferroptosis as a therapeutic strategy. In summary, this review enriched the insights of both investigators and practitioners, while fostering an elevated comprehension of ferroptosis and its latent translational utilities. By revealing the basic processes and investigating treatment possibilities, this review provides a crucial resource for scientists and medical practitioners, aiding in a deep understanding of ferroptosis and its effects in various disease situations., (© 2023. Sichuan International Medical Exchange & Promotion Association.)

Objectives: To elucidate the change in glutamate levels in preterm infants at different gestational ages by glutamate chemical exchange saturated transfer (GluCEST) magnetic resonance imaging and to compare the difference in glutamate levels among different brain regions between very early preterm infants and middle and late preterm infants., Methods: Fifty-three preterm infants (59% males; median gestational age = 33.6 weeks) underwent MRI, including conventional MRI and GluCEST. The original data were postprocessed in MATLAB. Correlation analysis was used to determine the relationship between the MTRasym and gestational age. The differences in MTRasym signals among different ROIs were statistically analysed by one-way analysis of variance (ANOVA). The MTRasym difference of the bilateral hemispherical ROI was compared by a paired T test., Results: In all ROIs, glutamate concentration was positively correlated with gestational age. The glutamate concentration in the thalamus was higher than that in the frontal lobe in very early, middle and late preterm infants. A difference in glutamate concentration was not found in the bilateral ROIs., Conclusions: The concentration of glutamate in the brains of preterm infants of different gestational ages increased with gestational age, which may be one of the factors contributing to the higher incidence of neurodevelopmental dysfunction in very early preterm infants compared to that in middle and late preterm infants. Meanwhile, the glutamate concentrations among different brain regions were also diverse., Key Points: • The glutamate concentration was positively correlated with gestational age in preterm infants of the brain. • Glutamate concentrations were dissimilar in different brain regions of preterm infants. • Glutamate concentration during the process of brain development in premature infants was not found to be asymmetric., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

N6-methyladenosine (m 6 A) RNA methylation and its associated RNA-binding protein insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) are involved in tumor initiation and progression. Here, we explored the biological function and clinical significance of IGF2BP1 in intrahepatic cholangiocarcinoma (iCCA). We found that IGF2BP1 expression was upregulated by H3K27 acetylation enrichment of its promoter, which positively correlated with poor clinicopathological characteristics and survival. Gain- and loss-of-function experiments showed that IGF2BP1 overexpression (knockdown) enhanced (attenuated) iCCA growth and metastasis in vitro and in vivo. Mechanistically, IGF2BP1 not only regulated the c-Myc/p16 axis to promote iCCA growth and inhibit senescence, but also activated the ZIC2/PAK4/AKT/MMP2 axis to induce tumor metastasis. More importantly, BTYNB, a recently identified IGF2BP1 inhibitor, exerted promising anti-tumor efficacy in a patient-derived xenograft (PDX) model, and IGF2BP1 conditional knockout (cKO) reduced the tumor burden. These results demonstrate the crucial role of IGF2BP1 in iCCA progression via m 6 A-dependent modification, highlighting IGF2BP1 as a potential therapeutic target in iCCA., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Gastric cancer (GC) is a leading cause of cancer-related death worldwide. Transcription factors (TFs) are essential gene expression regulators, and play critical roles in cancer development. However, the biological actions and prognostic value of TFs in GC remain unclear. In this study, we identified a risk model based on a 14-TF signature to predict recurrence-free survival in patients with GC. We further analyzed the ability of 14-TF to predict recurrence-free survival time in GC and found that a higher expression level of metastasis-associated protein 2 (MTA2) was associated with shorter overall survival and disease-free survival time in GC. Through in vitro and in vivo experiments, we demonstrated that MTA2 significantly promotes GC growth and metastasis. Furthermore, we identified MTA2 binding to the promoter of minichromosome maintenance deficient 5 (MCM5), thereby promoting GC progression. Overall, these findings strongly support the prognostic potential of the 14-TFs signature and suggest that targeting MTA2 may be a promising strategy to treat GC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Aims: To determine SNHG8's function and potential mechanisms in gastric cancer (GC) chemoresistance., Methods: We assessed SNHG8 expression in GC cell lines, GC/CDDP cell lines (cell lines treated with cisplatin), and 42 GC tissues and SNHG8 levels in the lncRNA microarray analysis of AGS/CDDP and AGS cell lines. We also examined GC cell viability in vivo and in vitro and its apoptosis level with Flow cytometry assays. SNHG8 was localized in subcells using fluorescence in situ hybridization (FISH) and cell fraction assays, hnRNPA1's link to SNHG8 was determined utilizing RNA immunoprecipitation (RIP) and FISH assays, gene expression profiles were assessed employing RNA transcriptome sequencing, and hnRNPA1's relationship with TROY was ascertained with the RIP assay., Results: SNHG8 increased significantly in GC cell lines and GC tissues. However, a decrease in its expression promoted sensitivity to chemotherapy and inhibited DNA damage repair in vitro and in vivo. SNHG8 appeared to regulate TROY expression via linking with hnRNPA1. Reducing TROY levels considerably stimulated GC cell chemosensitivity, whereas heightening them partially rescued the rate of chemoresistance caused by downregulating SNHG8., Conclusion: In summary, the "SNHG8/hnRNPA1-TROY" axis is crucial to GC chemoresistance., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Freund's complete adjuvant (FCA) and incomplete adjuvant (FIA), generally applied in subunit fishery vaccine, have not been explored on the molecular mechanism of the non-specific immune enhancement. As long noncoding RNAs (lncRNAs) play vital regulating roles in various biological activities, in this study, we examined the genome-wide expression of transcripts in the liver of European eel (Anguilla anguilla, Aa) inoculated with FCA and FIA (FCIA) to elucidate the regulators of lncRNAs in the process of Edwardsiella anguillarum (Ea) infection and Aa anti-Ea infection using strand-specific RNA-seq. After eels were challenged by Ea at 28 days post the first inoculation (dpi), compared to the control uninfected eels (Li group), the control infected eels (Con&#95;Li group) showed severe bleeding, hepatocyte atrophy, and thrombi formed in the hepatic vessels of the liver, although eels inoculated with FCIA (FCIA&#95;Li group) also formed slight thrombi in the hepatic vessels. Compared to the FCIA&#95;Li group, there was about 10 times colony-forming unit (cfu) in the Con&#95;Li group per 100 μg liver tissue, and the relative percent survival (RPS) of eels was 50% in FCIA&#95;Li vs Con&#95;Li. Using high-throughput transcriptomics, differential expressed genes (DEGs) and transcripts were identified and the results were verified using fluorescence real-time polymerase chain reaction (qRT-PCR). Interactions between the differential expressed lncRNAs (DE-lncRNAs) and the target DEGs were explored using Cytoscape according to their co-expression and co-location relationship. We found 13,499 lncRNAs (10,176 annotated and 3423 novel lncRNAs) between 3 comparisons of Con&#95;Li vs Li, FCIA&#95;Li vs Li, and FCIA&#95;Li vs Con&#95;Li, of which 111, 110, and 129 DE-lncRNAs were ascertained. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of DEGs targeted by DE-lncRNAs revealed these DEGs mainly involved in single-organism cellular process in BP, membrane in CC and binding in MF, and KEGG pathways showed that the target DEGs in co-expression and co-location enriched in cell adhesion molecules. Finally, 118 DE-lncRNAs target 1161 DEGs were involved in an interaction network of 8474 co-expression and 333 co-location-related links, of which 16 DE-lncRNAs play vital roles in anti-Ea infection. Taken together, the interaction networks revealed that DE-lncRNAs underlies the process of Ea infection and Aa anti-Ea infection., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study evaluates the progression of visual fatigue induced by visual display terminal (VDT) using automatically detected blink features. A total of 23 subjects were recruited to participate in a VDT task, during which they were required to watch a 120-min video on a laptop and answer a questionnaire every 30 min. Face video recordings were captured by a camera. The blinking and incomplete blinking images were recognized by automatic detection of the parameters of the eyes. Then, the blink features were extracted including blink number (BN), mean blink interval (Mean&#95;BI), mean blink duration (Mean&#95;BD), group blink number (GBN), mean group blink interval (Mean&#95;GBI), incomplete blink number (IBN), and mean incomplete blink interval (Mean&#95;IBI). The results showed that BN and GBN increased significantly, and that Mean&#95;BI and Mean&#95;GBI decreased significantly over time. Mean&#95;BD and Mean&#95;IBI increased and IBN decreased significantly only in the last 30 min. The blink features automatically detected in this study can be used to evaluate the progression of visual fatigue.

In this paper, a novel ANN flood forecasting model is proposed. The ANN model is combined with traditional hydrological concepts and methods, taking the initial Antecedent Precipitation Index (API), rainfall, upstream inflow and initial flow at the forecast river section as input of model, and flood flow forecast of the next time steps as output of the model. The distributed rainfall is realized as the input of the model. The simulation is processed by dividing the watershed into several rainfall-runoff processing units. Two hidden layers are used in the ANN, and the topology of ANN is optimized by connecting the hidden layer neurons only with the input which has physical conceptual causes. The topological structure of the proposed ANN model and its information transmission process are more consistent with the physical conception of rainfall-runoff, and the weight parameters of the model are reduced. The arithmetic moving-average algorithm is added to the output of the model to simulate the pondage action of the watershed. Satisfactory results have been achieved in the Mozitan and Xianghongdian reservoirs in the upper reaches of Pi river in Huaihe Basin, and the Fengman reservoir in the upper reach of Second Songhua river in Songhua basin in China., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background and Objective: Eyestrain has been increasingly severe in our lives and works as the progress of computers and smartphones. Evaluating eyestrain helps to prevent and relieve eyestrain. Our study aimed to evaluate eyestrain by analyzing vertical electrooculogram (VEOG)., Methods: 21 young subjects were asked to watch a video on the computer for a totally 120 minutes each, during which the VEOG signal was acquired using only three electrodes, and the questionnaire was answered every 30 minutes. The VEOG signal was divided into four 30-minute phases, from which VEOG signal power probability (VEOGSPP) features and blink features were extracted. The blink features include the changes of blink number (BN), group blinks number (GBN) and ratio (GBR), mean blink amplitude (Mean&#95;BA) and duration (Mean&#95;BD), mean blink duration at 50% (Mean&#95;BD50), mean closing duration (Mean&#95;CD) and opening duration (Mean&#95;OD), mean opening duration at early 50% (Mean&#95;ODE50) and late 50% (Mean&#95;ODL50), mean blink maximum rising slope (Mean&#95;BMRS) and falling slope (Mean&#95;BMFS)., Results: The results showed that the VEOGSPP in the high-frequency band (0.8-6.3Hz), BN, GBN, and GBR significantly increased while the VEOGSPP in the low-frequency band (0.1-0.4Hz), Mean&#95;BA, Mean&#95;OD, and Mean&#95;ODL50 significantly decreased with eyestrain (P<0.05)., Conclusions: In conclusion, eyestrain induced by watching videos for a long time could be well evaluated by analyzing the VEOG signal., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2021. Published by Elsevier B.V.)

Despite the fact that studies have revealed mechanisms underlying tumor chemoresistance, the functions of numerous potential chemoresistance-associated genes have yet to be elucidated. A bioinformatics analysis was conducted to screen differentially expressed genes (DEGs) across four types of chemoresistant tumors and functional enrichment analysis was used to examine the biological significance of these genes. Furthermore, a gene network was constructed using weighted gene co-expression network analysis to identify hub genes. A total of 6,015, 2,074, 2,141 and 954 differentially expressed genes were identified in estrogen receptor-negative breast cancer, ovarian cancer, rectal cancer and gastric cancer, respectively; however, only five of these DEGs were dysregulated in all four types of cancer. Functional enrichment analysis of the DEGs suggested that genomic stability and immune response are crucial determinants of tumor chemoresistance. In addition, 14, 8, 6 and 1 co-expressed gene modules were identified in estrogen receptor-negative breast cancer, ovarian cancer, rectal cancer and gastric cancer, respectively, and protein-protein interaction networks were created. The analysis identified only calcium-calmodulin-dependent protein kinase kinase 2, erythropoietin receptor, mitochondrial poly(A) RNA polymerase, α-parvin, and zinc finger and BTB domain-containing protein 44 to be dysregulated in all four cancer types, indicating varying mechanisms of chemoresistance in different tumor types. Furthermore, our analysis suggests that type I collagen α1, fibroblast growth factor 14 and major histocompatibility complex, class II, DR β1 potentially serve key roles in the development of chemoresistance. In conclusion, the present study proposes a simple and effective strategy for identifying genes involved in chemoresistance and predicting their potential functional roles, which may guide subsequent experimental studies.

The emergence of multiple drug resistance (MDR) is the main cause of chemotherapy failure in gastric cancer. In this study, to generate MDR gastric cancer cell lines, we exposed MKN45 and AGS gastric cancer cells to cisplatin, fluorouracil, and adriamycin. Through transcriptome sequencing, we found that interferon regulatory factor-1 (IRF-1) was expressed at significantly lower levels in the MDR cell lines than in the parental cell lines. We then established stable clones of MKN45 and SGC7901 cells with a doxycycline-inducible IRF-1 expression system and confirmed that IRF-1 overexpression efficiently reversed the MDR. Further analyses indicated that IRF-1 suppresses P-glycoprotein (P-gp) expression in vitro and in vivo, leading to an increase in chemotherapy drug retention. The results showed that IRF-1 bound to the promoter regions of P-gp gene and inhibited P-gp transcription. IFN-γ induced IRF-1-mediated downregulation of P-gp in gastric cancer cells. Finally, we demonstrated that the clinical correlation between IRF-1 and P-gp expression and that IRF-1 serves as an independent prognostic factor for patients with gastric cancer. We conclude that IRF-1 reverses the MDR trait of gastric cancer by downregulating P-gp, and this mechanism has potential treatment implications and is clinically actionable., (Copyright © 2019 Elsevier B.V. All rights reserved.)

MIR17HG, located on chromosome 13, is a class of Pri-miRNAs that generates six miRNAs: miR-17, miR-18a, miR-19a, miR-20a, miR-19b-1 and miR-92-1. These miRNAs are ubiquitously overexpressed in diverse tumour types and exhibit complex biological links to tumour metastasis. We demonstrated that MIR17HG-derived miR-18a and miR-19a coordinately mediate gastric cancer cell metastasis by directly inhibiting SMAD2 expression and upregulating Wnt/β-catenin signalling. Based on previous studies, we hypothesised that an investigation of MIR17HG inhibition would be beneficial to clinical gastric cancer treatment, and systematically coupled bioinformatics analyses brought interferon regulatory factor-1 (IRF-1) to our attention. We then established stable clones in gastric cancer cells containing a doxycycline-inducible IRF-1 expression system and found that the expression of IRF-1 downregulates the embedded miRNAs of MIR17HG in gastric cancer cells and inhibits gastric cancer cell metastasis by attenuating Wnt/β-catenin signalling. Further rescue assays confirmed the crucial roles of miR-18a and miR-19a in the IRF-1-mediated inhibition of Wnt/β-catenin signalling. We also demonstrated that IRF-1 binds to the transcriptional site in the MIR17HG promoter and inhibits MIR17HG expression. Moreover, IFN-γ induced the IRF-1-mediated downregulation of MIR17HG in gastric cancer cells. Our hypothesis was supported by the results of immunohistochemistry analyses of clinical gastric cancer samples, and we also demonstrated the role of IRF-1 in inhibiting MIR17HG expression and tumour metastasis in vivo. We conclude that IRF-1 inhibits gastric cancer metastasis by downregulating MIR17HG-miR-18a/miR-19a axis expression and attenuating Wnt/β-catenin signalling.

Gastric cancer is currently the fourth most common cancer and the third leading cause of cancer‑associated mortality worldwide. Studies have identified that certain biomarkers contribute to the prognosis, diagnosis and treatment of gastric cancer. However, the biomarkers of gastric cancer are rarely used clinically. Therefore, it is imperative to define novel molecular networks and key genes to guide the further study and clinical treatment of gastric cancer. In the present study, raw RNA sequencing data and clinicopathological information on patients with gastric cancer were downloaded from The Cancer Genome Atlas, and a weighted gene co‑expression network analysis was conducted. Additionally, functional enrichment and protein‑protein interaction analyses were implemented to further examine the significant modules. As a result, 16 modules of highly correlated genes were acquired and colour coded, and the yellow module containing 174 genes associated with chemotherapy resistance and prognosis in gastric cancer was further analysed. The biological processes of the yellow module were primarily associated with cell adhesion, vasculature development and the regulation of cell proliferation. In addition, the Kyoto Encyclopedia of Genes and Genomes pathways primarily involved the transforming growth factor‑β signalling pathway, the cellular tumour antigen p53 signalling pathway, extracellular matrix‑receptor interactions and focal adhesions. Notably, survival analysis and cell verification confirmed that high expression of GLIS family zinc finger 2 is significantly associated with chemoresistance and a worse prognosis in gastric cancer, and that this high expression is likely to be an important biomarker for the guidance of clinical treatment and prognostic evaluation.

Drug resistance is a primary cause of chemotherapeutic failure; however, how this resistance develops is complex. A comprehensive understanding of chemotherapeutic resistance mechanisms may aid in identifying more effective drugs and improve the survival rates of patients with cancer. Insulin-like growth factor 1 receptor (IGF1R), a member of the insulin receptor family, has been extensively assessed for biological activity, and its putative contribution to tumor cell development and progression. Furthermore, researchers have attended to drugs that target IGF1R since IGF1R functions as a membrane receptor. However, how IGF1R participates in chemotherapeutic resistance remains unclear. Therefore, the present study described the IGF1R gene and its associated signaling pathways, and offered details of IGF1R-induced tumor chemoresistance associated with promoting cell proliferation, inhibition of apoptosis, regulation of ATP-binding cassette transporter proteins and interactions with the extracellular matrix. The present study offered additional explanations for tumor chemotherapy resistance and provided a theoretical basis of IGF1R and its downstream pathways for future possible chemotherapy treatment options.

Background: CDX2 is a caudal-homeobox gene and its expression is abnormal in numerous tumour cell types. Nevertheless, its prognostic value for solid tumours requires further investigation. Hence, we conducted a meta-analysis to determine the significance of CDX2 as a prognostic biomarker in solid malignancies systematically., Materials and Methods: We performed a systematic literature search in PUBMED and EMBASE up to May 2017. Retrospective studies comparing the prognostic value of different CDX2 levels in human malignancies were included. Data extractions and methodological assessments were performed separately by two investigators using a standard procedure. The statistical procedures were performed using Review Manager 5.3 and STATA/MP 14.0., Results: A total of 26 retrospective studies met the inclusion criteria and comprised 5008 participants. Patients with CDX2 overexpression had significantly better 3-year, 5-year, 10-year and disease-free survival outcomes in solid malignancies, regardless of the cancer type, mean age, and source region. Nevertheless, there was no significant difference in the patients from Europe. The expression level of CDX2 was not statistically associated with cancer relapse. Moreover, our analysis showed that CDX2 overexpression is correlated to better responses to chemotherapy in patients with TNM IV stage cancers. The stability of the pooled outcomes was verified by sensitivity analysis. The funnel plots, Egger's test and Begg's test jointly confirmed that there was no publication bias., Conclusions: Overexpression of CDX2 is a reliable biomarker of a better prognosis in solid malignancies., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Objectives: The objectives of this paper were to investigate the clinicopathological characteristics and prognostic factors of GI-bleeding GIST patients and explore whether GI bleeding is a risk factor for GIST relapse., Methods: Primary GIST patients with initial symptoms of GI bleeding or no GI bleeding were retrospectively studied., Results: Up to 178 GI-bleeding GIST patients including 108 (60.7%) males and 70 (39.3%) females were evaluated for the clinicopathological characteristics. The stomach, small bowel, and colorectum were the tumor sites in 82 (46.1%), 85 (47.8%), and 11 (6.2%) patients. Of the 178 patients, 163 GI-bleeding patients had follow-up while another 363 patients from the total population presented without GI bleeding were followed up. Up to 526 patients who received postoperative follow-up were included in the survival analysis. Compared with the 363 non-GI-bleeding patients, GI-bleeding patients developed smaller tumors (P = 0.015) and had a longer relapse-free survival (RFS; P = 0.014). For the 163 GI-bleeding patients, a Cox regression analysis showed that the mitotic count and the platelet-lymphocyte ratio before surgery were independent prognostic predictors for poor outcome regarding RFS. For all 526 patients, a Cox regression analysis indicated that tumor location, mitotic index, platelet-lymphocyte ratio, and GI bleeding were independent prognosis predictors., Conclusion: Compared to non-GI-bleeding GIST patients, patients with GI bleeding were more likely to be male and to have more small intestine GISTs, smaller tumors, and a longer RFS. For GI-bleeding patients, mitotic count and platelet-lymphocyte ratio were independent prognostic indicators. GI bleeding served as a surrogate for smaller GIST and was a protective factor for GIST recurrence.