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Abstract Background Colorectal cancer (CRC) is the most common gastrointestinal malignancy worldwide, with obesity-induced lipid metabolism disorders playing a crucial role in its progression. A complex connection exists between gut microbiota and the development of intestinal tumors through the microbiota metabolite pathway. Metabolic disorders frequently alter the gut microbiome, impairing immune and cellular functions and hastening cancer progression. Methods This study thoroughly examined the gut microbiota through 16S rRNA sequencing of fecal samples from 181 CRC patients, integrating preoperative Low-density lipoprotein cholesterol (LDL-C) levels and RNA sequencing data. The study includes a comparison of microbial diversity, differential microbiological analysis, exploration of the associations between microbiota, tumor microenvironment immune cells, and immune genes, enrichment analysis of potential biological functions of microbe-related host genes, and the prediction of LDL-C status through microorganisms. Results The analysis revealed that differences in α and β diversity indices of intestinal microbiota in CRC patients were not statistically significant across different LDL-C metabolic states. Patients exhibited varying LDL-C metabolic conditions, leading to a bifurcation of their gut microbiota into two distinct clusters. Patients with LDL-C metabolic irregularities had higher concentrations of twelve gut microbiota, which were linked to various immune cells and immune-related genes, influencing tumor immunity. Under normal LDL-C metabolic conditions, the protective microorganism Anaerostipes_caccae was significantly negatively correlated with the GO Biological Process pathway involved in the negative regulation of the unfolded protein response in the endoplasmic reticulum. Both XGBoost and MLP models, developed using differential gut microbiota, could forecast LDL-C levels in CRC patients biologically. Conclusions The intestinal microbiota in CRC patients influences the LDL-C metabolic status. With elevated LDL-C levels, gut microbiota can regulate the function of immune cells and gene expression within the tumor microenvironment, affecting cancer-related pathways and promoting CRC progression. LDL-C and its associated gut microbiota could provide non-invasive markers for clinical evaluation and treatment of CRC patients.

Ion interference, including intracellular copper (Cu) overload, disrupts cellular homeostasis, triggers mitochondrial dysfunction, and activates cell-specific death channels, highlighting its significant potential in cancer therapy. Nevertheless, the insufficient intracellular Cu ions transported by existing Cu ionophores, which are small molecules with short blood half-lives, inevitably hamper the effectiveness of cuproptosis. Herein, the ESCu@HM nanoreactor, self-assembled from the integration of H-MnO2 nanoparticles with the Cu ionophore elesclomol (ES) and Cu, was fabricated to facilitate cuproptosis and further induce relevant immune responses. Specifically, the systemic circulation and tumoral accumulation of Cu, causing irreversible cuproptosis, work in conjunction with Mn2+, resulting in the repolarization of tumor-associated macrophages (TAMs) and amplification of the activation of the cGAS-STING pathway by damaged DNA fragments in the nucleus and mitochondria. This further stimulates antitumor immunity and ultimately reprograms the tumor microenvironment (TME) to inhibit tumor growth. Overall, ESCu@HM as a nanoreactor for cuproptosis and immunotherapy, not only improves the dual antitumor mechanism of ES and provides potential optimization for its clinical application, but also paves the way for innovative strategies for cuproptosis-mediated colorectal cancer (CRC) treatment.

ABSTRACT Introduction Isobutyric acid (IBA), a short‐chain fatty acid, has been unequivocally demonstrated to exert significant influence on the progression of colorectal cancer (CRC). Nevertheless, a comprehensive understanding of its intricate regulatory mechanisms remains elusive. Methods Employing advanced techniques such as western blot, RT‐qPCR, and flow cytometry, we systematically investigated the impact of IBA on the expression of PD‐L1 in CRC cells. Concurrently, employing RNA silencing technology and small‐molecule inhibitors, we delved into the molecular intricacies underlying the regulatory axis of IBA involving ROCK1/c‐Myc/PD‐L1. Furthermore, through flow cytometry analysis, we examined the alterations in the tumor immune microenvironment following anti‐PD‐L1 antibody therapy in a murine tumor model treated with IBA. Results Elevated levels of IBA were found to robustly activate PD‐L1 expression in CRC cells both in vitro and in vivo, concomitantly reshaping the tumor immune microenvironment. Subsequent mechanistic investigations unveiled that IBA, through its interaction and activation of ROCK1, promotes the activation of c‐Myc, thereby enhancing the transcription of PD‐L1. Silencing of ROCK1 and application of ROCK1 inhibitors effectively reversed the regulatory effects of IBA on PD‐L1. Additionally, IBA inhibited the activity of infiltrating CD8+ T cells, resulting in diminished antitumor immunity and attenuating the sensitivity to anti‐PD‐L1 therapy. Conclusion Our study elucidates a novel mechanism by which IBA inhibits the sensitivity of CRC to anti‐PD‐L1 antibody therapy. Emphasizing IBA and its downstream pathways as potential therapeutic targets for immune therapy resistance mechanisms, our findings provide a novel theoretical foundation for overcoming immune therapy resistance.

Water-lubricating bearings made of polymer-matrix composites have provided a new approach to prolong the service lifetime of key component in marine propulsion system. However, it was still crucial to find a convenient and effective material to manufacture the water-lubricating bearing with ultralow friction. Herein, a new kind of polyetheretherketone (PEEK) composite with ultralow coefficient of friction (COF), high mechanical strength and thermal stability has been developed. An 80.7% decrease in the COF of PEEK was achieved by incorporating the fillers. A possible mechanism between the heterogeneous nucleation and mobility hindrance of PEEK chain segment caused by different fillers was proposed. The ultralow COF endowed the water-lubricating bearing with low running noise and reduced energy consumption. The high mechanical strength and thermal stability caused the superior carrying capacity and reliability. Therefore, the prepared PEEK composites can be a possibility to realize the water-lubricating bearing with high durability and long service lifetime.

Background: Accumulating studies have found that circular RNAs (circRNAs) have a regulatory effect in a variety of tumors. However, to date, the relationship between specific circRNAs and colorectal cancer (CRC) remains elusive. Methods: An RNA-sequencing method based on different metastatic potential of CRC cell lines was applied to evaluate the circRNA expression profile. Additionally, we conducted a series of experiments to assess the relationship between circRNAs and CRC progression. Results: Circ_0001742 was upregulated in CRC cells with high metastatic potential, and circ_0001742 overexpression was observed to facilitate proliferation, migration and metastasis while knockdown will inhibit. More importantly, we found that circ_0001742 acted as a sponge for miR-431-5p, thus affecting ALG8 levels and the development of CRC. Conclusions: This study demonstrated an essential function for the circ_0001742/miR-431-5p/ALG8 axis in CRC development, and it may be a promising therapeutic target for CRC.

Abstract Background Overweight is known to be an important risk factor for colorectal cancer (CRC), and the differences in intestinal flora among CRC patients with different BMI status have not been clearly defined. The purpose of this study was to elucidate the differences in the abundance, composition and biological function of intestinal flora in CRC patients with different BMI status. Method A total of 170 CRC patients were included and grouped according to the BMI data of CRC patients. BMI ≥ 24 kg/m2 was defined as overweight group, and BMI within the range of 18.5–23.9 kg/m2 was defined as normal weight group. Preoperative stool collection of patients in both groups was used for 16S rRNA sequencing. Total RNA was extracted from 17 CRC tumor tissue samples for transcriptome sequencing, and then CIBERSORT algorithm was used to convert the transcriptome data into the relative content matrix of 22 kinds of immune cells, and the correlation between different intestinal flora and immune cells and immune-related genes under different BMI states was analyzed. Finally, we identified BMI-related differential functional pathways and analyzed the correlation between these pathways and differential intestinal flora. Result There was no significant difference in α diversity and β diversity analysis between overweight group and normal weight group. Partial least square discriminant analysis (PLS-DA) could divide the flora into two different clusters according to BMI stratification. A total of 33 BMI-related differential flora were identified by linear discriminant effect size analysis (LEfSe), among which Actinomyces, Desulfovibrio and Bacteroides were significantly enriched in overweight group. ko00514: Other types of O-glycan biosynthesis are significantly enriched in overweight group. There was a significant positive correlation between Clostridium IV and Macrophages M2 and T cells regulatory (Tregs). There was a significant negative correlation with Dendritic cells activated and T cells CD4 memory activated. Conclusions The richness and diversity of intestinal flora of CRC patients may be related to different BMI status, and the enrichment of Actinomyces, Desulphurvibrio and Bacteroides may be related to overweight status of CRC patients. The tumor microenvironment in which BMI-related differential flora resides has different immune landscapes, suggesting that some intestinal flora may affect the biological process of CRC by regulating immune cell infiltration and immune gene expression, but further experiments are needed to confirm this.

Abstract Heat shock proteins play crucial roles in various biochemical processes, encompassing protein folding and translocation. HSP90B1, a conserved member of the heat shock protein family, growing evidences have demonstrated that it might be closely associated with cancer development. In the present study, we employed multi-omics analyses and cohort validations to explore the dynamic expression of HSP90B1 in pan-cancer and comprehensively evaluate HSP90B1 as a novel biomarker that hold promise for precision cancer diagnostics and therapeutics. The results suggest HSP90B1 was highly expressed in various kinds of tumors, often correlating with a poor prognosis. Notably, methylation of HSP90B1 emerged as a protective factor in several cancer types. In immune infiltration analysis, the expression of HSP90B1 in most tumors showed a negative association with CD8 + T cells. HSP90B1 expression was positively correlated with microsatellite instability and tumor mutational burden. HSP90B1 expression was also discovered to be positively correlated with tumor metabolism, cell cycle-related pathways and the expression of immune checkpoint genes. The expression of HSP90B1 was mainly negatively correlated with immunostimulatory genes and positively correlated with immunosuppressive genes, as well as strongly correlated with chemokines and their receptor genes. In addition, the HSP90B1 inhibitor PU-WS13 demonstrated significant efficacy in suppressing cancer cell proliferation in both leukemic and solid tumor cells, and remarkably reduced the expression of the cancer cell surface immune checkpoint PD-L1. The single-cell RNA sequencing analysis further highlighted that HSP90B1 was significantly higher in tumor cells compared to surrounding cells, revealing a potential target therapeutic window. Taken together, HSP90B1 emerges as a promising avenue for breakthroughs in cancer diagnosis, prognosis and therapy. This study provides a rationale for HSP90B1 targeted cancer diagnosis and therapy in future.

Abstract Ferroptosis is an iron-dependent form of cell death induced by lipid oxidation with an essential role in diseases, including cancer. Since prognostic value of ferroptosis-dependent related genes (FDRGs) in colorectal cancer (CRC) remains unclear, we explored the significance of FDRGs in CRC through comprehensive single-cell analysis. We downloaded the GSE161277 dataset for single-cell analyses and calculated the ferroptosis-dependent gene score (FerrScore) for each cell type. According to each cell type-specific median FerrScore, we categorized the cells into low- and high-ferroptosis groups. By analyzing differentially-expressed genes across the two groups, we identified FDRGs. We further screened these prognosis-related genes used to develop a prognostic signature and calculated its correlation with immune infiltration. We also compared immune checkpoint gene efficacy among different risk groups, and qRT-PCR was performed in colorectal normal and cancer cell lines to explore whether the signature genes could be used as clinical prognostic indicators. In total, 523 FDRGs were identified. A prognostic signature including five signature genes was constructed, and patients were divided into two risk groups. The high-risk group had poor survival rates and displayed high levels of immune infiltration. Our newly developed ferroptosis-based prognostic signature possessed a high predictive ability for CRC.

Abstract Objective The relationship between intestinal microbiome and colorectal cancer (CRC) progression is unclear. This study aims to identify the intestinal microbiome associated with CRC progression and construct predictive labels to support the accurate assessment and treatment of CRC. Method The 192 patients included in the study were divided into stage I-II and stage III-IV CRC patients according to the pathological stages, and preoperative stools were collected from both groups for 16S rDNA sequencing of the intestinal microbiota. Pearson correlation and Spearman correlation coefficient analysis were used to analyze the differential intestinal microbiome and the correlation with tumor microenvironment and to predict the functional pathway. XGBoost model (XGB) and Random Forest model (RF) were used to construct the microbiome-based signature. The total RNA extraction from 17 CRC tumor simples was used for transcriptome sequencing. Result The Simpson index of intestinal microbiome in stage III-IV CRC were significantly lower than those in stage I-II CRC. Proteus, Parabacteroides, Alistipes and Ruminococcus etc. are significantly enriched genus in feces of CRC patients with stage III-IV. ko00514: Other types of O − glycan biosynthesis pathway is relevant with CRC progression. Alistipes indistinctus was positively correlated with mast cells, immune activators IL-6 and IL6R, and GOBP_PROTEIN_FOLDING_IN_ENDOPLASMIC_RETICULUM dominantly. The Random Forest (RF) model and eXtreme Gradient Boosting (XGBoost) model constructed with 42 CRC progression-associated differential bacteria were effective in distinguishing CRC patients between stage I-II and stage III-IV. Conclusions The abundance and diversity of intestinal microbiome may increase gradually with the occurrence and progression of CRC. Elevated fetal abundance of Proteus, Parabacteroides, Alistipes and Ruminococcus may contribute to CRC progression. Enhanced synthesis of O − glycans may result in CRC progression. Alistipes indistinctus may play a facilitated role in mast cell maturation by boosting IL-6 production. Alistipes indistinctus may work in the correct folding of endoplasmic reticulum proteins in CRC, reducing ER stress and prompting the survival and deterioration of CRC, which may owe to the enhanced PERK expression and activation of downstream UPR by Alistipes indistinctus. The CRC progression-associated differential intestinal microbiome identified in our study can be served as potential microbial markers for CRC staging prediction.

Small round cell undifferentiated sarcoma is a rare and highly invasive group of malignant bone and soft tissue tumors, often associated with a high misdiagnosis rate. The patient in this case was a 34-year-old male who presented with a two-month history of abdominal pain that worsened over the past two weeks. Elevated levels of tumor markers CA19-9 and CA72-4 were observed. Imaging revealed a substantial, well-vascularized mass in the lower left abdomen, located in the posterior abdominal cavity, invading the descending colon and the root of the small mesentery, and infiltrating the serous layer. The lesion was extensively resected without any postoperative complications. Microscopic examination indicated a combination of mucinous adenocarcinoma (approximately 30%) and small round cell undifferentiated sarcoma (approximately 70%). The patient was followed up for six months, and one month after surgery, a recurrence of the tumor was observed in the left paracolonic sulcus area, with metastases to the abdominal wall, peritoneum, and medial iliac muscles. Chemotherapy and targeted therapy were administered, and the patient currently survives with the presence of tumors. Small round cell undifferentiated sarcoma is an uncommon and highly invasive tumor, and clinical surgeons need to raise their awareness and realize to the maximum extent possible that this disease can be described through a multi-modal combination of immunohistochemistry and genetic test to improve diagnostic accuracy and reduce missed diagnoses. Further research in the field of biology is necessary to explore targeted drugs specifically suitable for this disease.

Abstract Background The intent of this research was to generate and investigate the D-dimer to lymphocyte ratio (DLR) capacity to forecast the risk and prognosis of colorectal cancer liver metastases (CRCLM). Methods From January 2010 to December 2019, 177 clinicopathologically confirmed colorectal cancer (CRC) patients (89 in the control group and 88 in the experimental group) were identified at the Affiliated Cancer Hospital of Guangxi Medical University. Multivariate Cox regression analysis was used to screen independent predictive diagnostic and prognostic factors of liver metastasis in CRC, and receiver operating characteristic (ROC) curves and Kaplan‒Meier (K‒M) curves were established to analyze the diagnostic and predictive prognostic efficacy of the DLR in the development of CRCLM. Results Patients with CRCLM had higher DLR levels and D-dimer levels in their blood, with statistically significant differences (p

The development of artificial intelligence and virtual reality technology has enabled rehabilitation service systems based on virtual scenarios to provide patients with a multi-sensory simulation experience. However, the design methods of most rehabilitation service systems rarely consider the physician–manufacturer synergy in the patient rehabilitation process, as well as the problem of inaccurate quantitative evaluation of rehabilitation efficacy. Thus, this study proposes a design method for a smart rehabilitation product service system based on virtual scenarios. This method is important for upgrading the rehabilitation service system. First, the efficacy of rehabilitation for patients is quantitatively assessed using multimodal data. Then, an optimization mechanism for virtual training scenarios based on rehabilitation efficacy and a rehabilitation plan based on a knowledge graph are established. Finally, a design framework for a full-stage service system that meets user needs and enables physician–manufacturer collaboration is developed by adopting a “cloud-end-human” architecture. This study uses virtual driving for autistic children as a case study to validate the proposed framework and method. Experimental results show that the service system based on the proposed methods can construct an optimal virtual driving system and its rehabilitation program based on the evaluation results of patients’ rehabilitation efficacy at the current stage. It also provides guidance for improving rehabilitation efficacy in the subsequent stages of rehabilitation services.

Abstract Abnormal epigenetic regulation is identified to correlate with cancer progression and renders tumor refractory and resistant to reactive oxygen species (ROS)‐based anti‐tumor actions. To address it, a sequential ubiquitination and phosphorylation epigenetics modulation strategy is developed and exemplified by the well‐established Fe‐metal‐organic framework (Fe‐MOF)‐based chemodynamic therapy (CDT) nanoplatforms that load the 26S proteasome inhibitor (i.e., MG132). The encapsulated MG132 can blockade 26S proteasome, terminate ubiquitination, and further inhibit transcription factor phosphorylation (e.g., NF‐κB p65), which can boost pro‐apoptotic or misfolded protein accumulations, disrupt tumor homeostasis, and down‐regulate driving genes expression of metastatic colorectal cancer (mCRC). Contributed by them, Fe‐MOF‐unlocked CDT is magnified to considerably elevate ROS content for repulsing mCRC, especially after combining with macrophage membrane coating‐enabled tropism accumulation. Systematic experiments reveal the mechanism and signaling pathway of such a sequential ubiquitination and phosphorylation epigenetics modulation and explain how it could blockade ubiquitination and phosphorylation to liberate the therapy resistance to ROS and activate NF‐κB‐related acute immune responses. This unprecedented sequential epigenetics modulation lays a solid foundation to magnify oxidative stress and can serve as a general method to enhance other ROS‐based anti‐tumor methods.

Background: Gastric cancer is one of the most common malignancies in the world and ranks fourth among cancer-related causes of death. Gastric adenocarcinoma is the most common pathological type of gastric cancer; usually, this tumor is associated with distant metastasis upon first diagnosis and has a poor prognosis. Cuproptosis is a novel mechanism of cell death induced by copper, and is closely related to tumor progression, prognosis and immune response. However, the role of cuproptosis-related genes (CRGs) in the tumor microenvironment (TME) of gastric cancer has yet to be elucidated. Methods: Gastric adenocarcinoma data were downloaded from the Cancer Genome Atlas (TCGA) database. Through bioinformatics analysis, a risk scoring model was constructed from cuproptosis gene-related lncRNA. Then, we investigated the relationship between prognosis and the TIME of gastric cancer according to clinical characteristics and risk score. Results: Validation of the model showed that the overall survival (OS) of the high-risk group was significantly lower than that of the low-risk group (P

The sensitive detection of antioxidants in food is essential for the rational control of their usage and reducing potential health risks. A simple three-dimensional (3D) electrode integrated with an anti-fouling/anti-interference layer possesses great potential for the direct and sensitive electrochemical detection of antioxidants in food samples. In this work, a 3D electrochemical sensor was developed by integrating a 3D graphene electrode (3DG) with vertically ordered mesoporous silica film (VMSF), enabling highly sensitive detection of the common antioxidant, butylated hydroxyanisole (BHA), in food samples. A simple electrochemical polarization was employed to pre-activate the 3DG electrode (p3DG), enhancing its hydrophilicity. Using the p3DG as the supporting electrode, stable modification of VMSF was achieved using the electrochemical assisted self-assembly (EASA) method, without the need for any adhesive agents (VMSF/p3DG). Taking BHA in food as a model analyte, the VMSF/p3DG sensor demonstrated high sensitivity, due to the enrichment by nanochannels, towards BHA. Electrochemical detection of BHA was achieved with a linear range of 0.1 μM to 5 μM and from 5 μM to 150 μM with a low limit of detection (12 nM). Owing to the fouling resistance and anti-interference capabilities of VMSF, the constructed 3D electrochemical sensor can be directly applied for the electrochemical detection of BHA in complex food samples.

ObjectiveTo identify differences between the composition, abundance, and biological function of the intestinal microbiome of patients with and without lymph-vascular invasion (LVI) colorectal cancer (CRC) and to construct predictive labels to support accurate assessment of LVI in CRC.Method134 CRC patients were included, which were divided into two groups according to the presence or absence of LVI, and their intestinal microbiomes were sequenced by 16SrRNA and analyzed for differences. The transcriptome sequencing data of 9 CRC patients were transformed into immune cells abundance matrix by CIBERSORT algorithm, and the correlation among LVI-associated differential intestinal microbiomes, immune cells, immune-related genes and LVI-associated differential GO items and KEGG pathways were analyzed. A random forest (RF) and eXtreme Gradient Boosting (XGB) model were constructed to predict the LVI of CRC patients based on the differential microbiome.ResultThere was no significant difference in α-diversity and β-diversity of intestinal microbiome between CRC patients with and without LVI (P > 0.05). Linear discriminant analysis Effect Size (LEfSe) analysis showed 34 intestinal microbiomes enriched in CRC patients of the LVI group and 5 intestinal microbiomes were significantly enriched in CRC patients of the non-lymph-vascular invasion (NLVI) group. The RF and XGB prediction models constructed with the top 15% of the LVI-associated differential intestinal microbiomes ranked by feature significance had good efficacy.ConclusionsThere are 39 intestinal flora with significantly different species abundance between the LVI and NLVI groups. g:Alistipes.s:Alistipes_indistinctus is closely associated with colorectal cancer vascular invasion. LVI-associated differential intestinal flora may be involved in regulating the infiltration of immune cells in CRC and influencing the expression of immune-related genes. LVI-associated differential intestinal flora may influence the process of vascular invasion in CRC through a number of potential biological functions. RF prediction models and XGB prediction models constructed based on microbial markers of gut flora can be used to predict CRC-LVI conditions.

Background: Colon cancer (CC) is the fifth most prevalent cancer around the globe and poses a major risk to human health. Even though Kremen2 serves as a prognostic indicator in individuals with malignant tumours, its role in evaluating the prognosis of individuals with colon cancer has not been confirmed.Methods: Here, we examined the protein expression of Kremen2 in CC tissues and paired adjacent normal tissues by immunohistochemistry (IHC), then analyzed the clinical and RNA-seq data presented in The Cancer Genome Atlas (TCGA) database to confirm the relationship between Kremen2 levels and CC. In addition, the associations between Kremen2 mRNA expression and infiltrating immune cells were examined.Results: The study showed that the mRNA expression and protein level of Kremen2 were increased in CC tissues compared with adjacent normal tissues. According to Kaplan–Meier analysis, high Kremen2 expression in CC was linked to poor overall survival and progression-free survival. Clinical correlation analysis highlighted that a high level of Kremen2 expression was strongly linked with tumour progression, particularly lymph node metastasis. Cox regression analysis highlighted that Kremen2 was an independent prognostic indicator for CC. Bioinformatic studies highlighted that Kremen2 might be associated with the immune status in CC.Conclusion: Increased Kremen2 could serve as a potential prognostic CC biomarker.

Purpose The aim of the current study was to identify the relationship between body composition changes during neoadjuvant therapy (NAT) and the treatment efficiency of NAT in gastrointestinal cancer (GC) patients. Methods From January 2015 to July 2020, 277 GC patients treated with NAT had included for retrospective analysis. The body mass index (BMI) and computed tomography (CT) imaging before and after NAT were recorded. The BMI change optimal cut-off value were calculated by ROC curve. Balancing essential characteristic variables using propensity score matching (PSM) method. Exploring the association between BMI changes and tumor response to NAT using logistic regression analysis. The survival outcome of matched patients between different BMI change groups was compared. Results A cutoff point of BMI change >2% during NAT was defined as BMI loss. Among the 277 patients, 110 (39.7%) patients showed BMI change with a loss after NAT. In total, 71 pairs of patients were selected for further analysis. The median follow-up time was 22 months (range 3 to 63 months). Univariate and multivariate logistic regression analyses in matched cohort showed that BMI change was a prognostic factor for tumor response after NAT in GC patients (odds ratio (OR), .471; 95% confidence interval (CI), .233-.953; P = .036). In addition, patients who experienced BMI loss after NAT showed worse overall survival than those who had BMI gain or stable. Conclusion BMI loss during NAT probably may has negative effects on NAT efficiency and survival for gastrointestinal cancer patients. It is necessary to monitor and maintain weight for patients during treatment.

In Industry 4.0, medical data present a trend of multisource development. However, in complex information networks, an information gap often exists in data exchange between doctors and patients. In the case of diseases with complex manifestations, doctors often perform qualitative analysis, which is macroscopic and fuzzy, to present treatment recommendations for patients. Improving the reliability of data acquisition and maximizing the potential of data, require attention. To solve these problems, a multimodal data-driven rehabilitation strategy auxiliary feedback method is proposed. In this study, depth sensor and functional near-infrared spectroscopy (fNIRS) were used to obtain ethology and brain function data, and skeleton tracking analysis and ethology discrete statistics were performed to assist the diagnostic feedback of rehabilitation strategies. This study takes rhythm rehabilitation training of autistic children as a case, and results show that the multimodal data-driven rehabilitation strategy auxiliary feedback method can provide effective feedback for individuals or groups. The proposed auxiliary decision method increases the dimension of data analysis and improves the reliability of analysis. Through discrete statistical results, the potential of data are maximized, thereby assisting the proposed rehabilitation strategy diagnostic feedback.

Introduction: Low anterior resection syndrome (LARS) is the most common complication after total mesorectal excision (TME) in patients with low rectal cancer and has been a challenge in colorectal surgery that severely impacts the quality of life of patients. This study aimed to introduce a revised surgical procedure which could effectively maintain rectal compliance and significantly improve LARS after the operation. Methods: We performed mesorectal reconstruction after routine Dixon TME using greater omental pedicle flap transplantation in 11 patients with low rectal cancer (5 cases of preoperative neoadjuvant chemoradiotherapy, 5 cases of preoperative neoadjuvant chemotherapy, and 1 case of postoperative adjuvant chemotherapy), thereby simulating the initial anatomical structure of the mesorectum and significantly reducing the postoperative anterior resection syndrome. The lars precision syndrome assessment scale (LARSS) was used to access the LARS. Results: At 12 weeks after the 11 patients recovered from the anal defecation function, the average score on the LARS questionnaire was 25.5 ± 1.5 (minor). The average time at which anal function began to recover was 6.2 ± 2.6 weeks after surgery. The recovery was rapid, as the rectal and anal function of all patients generally returned to normal levels within 12 weeks, and the quality of life was close to that before surgery. Conclusion: Greater omental flap transplantation can significantly improve LARS after Dixon TME in patients with low rectal cancer.

Background: The SERPINH1 gene plays a vital part in tumorigenesis and development, whereas its potential as an immunotherapy target is still unknown. Hence, this research aimed to probe the roles of SERPINH1 in human tumors.Method: Using The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) database, Oncomine, and SangerBox software, the pan-cancer expression of SERPINH1 and its correlation were systematically analyzed. SERPINH1 protein information was detected by the Human Protein Atlas (HPA) database and STRING database. The genomic alterations of SERPINH1 were studied using the c-BioPortal database. The influence of SERPINH1 on prognosis was analyzed using Kaplan–Meier plotter. The R package “clusterProfiler” was used for enrichment analysis to detect the role of SERPINH1. The TIMER2 database was used to further analyze the correlation between the immune cell infiltration score of TCGA samples and the expression of SERPINH1.Results: SERPINH1 overexpression was related to worse survival status in pan-cancer. In addition, high expression of SERPINH1 was positively associated with tumor stage and poor prognosis. Moreover, SERPINH1 played an important role in tumor microenvironment and immune regulation. Our study revealed that SERPINH1 expression has a strong correlation with immune cell filtration, immune regulation, chemokines, and immune checkpoints.Conclusion: Our research found that SERPINH1 was a risk factor and predictor of poor prognosis in various tumors. High expression of SERPINH1 may contribute to tumor immune-suppressive status. Also, SERPINH1 may become a potential immunotherapy target in pan-cancer.

Introduction: POLD2 is an indispensable subunit of DNA polymerase δ, which is responsible for the synthesis of the backward accompanying strand in eukaryotic organisms. Current studies have found an association between POLD2 and the development of a variety of cancers. However, its value in cancer immunotherapy has not been fully established.Methods: POLD2 expression was analyzed using RNA expression and clinical data from TCGA and GTEx databases. The prognostic impact of POLD2 on tumor patients was analyzed using clinical survival data from TCGA. Gene enrichment analysis was performed using the R package “cluster analyzer” to explore the role of POLD2. We used the TIMER2 database to analyze the relationship between immune cell infiltration and POLD2 expression in TCGA. We downloaded relevant data from TCGA and analyzed the relationship between POLD2 and immune checkpoints, immunosuppressive genes, immune activating genes, chemokines and chemokine receptors.Results: POLD2 was significantly overexpressed in most tumors compared to normal tissue. High POLD2 expression was significantly associated with advanced tumor stage, significantly shorter overall survival and progression-free survival. Also, we found that POLD2 expression correlated strongly with immunomodulatory genes, and significantly negatively with most immune checkpoints (PD-L1, CTLA4, TIM3, and CD28). Pathway enrichment analysis suggests that low expression of POLD2 promotes immune regulation-related pathways and high expression promotes metabolic and DNA repair-related pathways. Furthermore, tumor microenvironment analysis suggests that high POLD2 expression inhibits infiltration of CD8+ T cells and CD4+ memory T cells.Discussion: In conclusion, POLD2 may be a molecular biomarker for pan-cancer prognosis and immunotherapy. It may serve as a potential target for new insights in human tumor prognosis prediction and immunotherapy assessment.

BackgroundThe contribution of hepatitis B virus (HBV) and hepatitis C virus (HCV) to primary liver cancer (PLC) and their association with cancer aggressiveness remains uncertain in China, a country with half of global PLC. We aimed to characterize this using data from four representative medical centers.MethodsIn total, 15,801 PLC patients were enrolled from the centers distributed in Easter5n, Southern, Northern, and Western China from 2003 to 2020. Of those, 7585 with curative surgery were involved in survival analysis. A nomogram was constructed using preoperative parameters to predict postoperative survival.ResultsHepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma, and combined hepatocellular cholangiocarcinoma accounted for 93.0%, 4.3%, and 1.6% in PLC, respectively. The seropositivities of HBV and HCV were 84.4% and 3.2% in HCC, respectively. The seropositivity of anti-HCV antibody was significantly higher in HBV-negative than in HBV-positive HCC patients (13.2% vs. 1.1%). Compared to HCV-positive HCC (HCV-HCC), HBV-positive HCC (HBV-HCC) was associated with 12-year earlier onset, higher proportions of males, high α-fetoprotein, large tumor size, advanced Barcelona Clinic Liver Cancer (BCLC) stage, and vascular tumor thrombus. The proportions of HCC and HBV seropositivity increased, whereas that of anti-HCV decreased, from 2003 to 2020. Postoperative five-year survival rate was 73.5%, 64.1%, 34.9%, and 19.7% in HCC at BCLC stage 0, A, B, and C, respectively. The multivariate Cox regression analysis showed that HBV seropositivity, incomplete tumor capsule, vascular tumor thrombus, tumor diameter (≥3 cm), advanced BCLC stage (B+C), α-fetoprotein (≥20ng/ml), and direct bilirubin (>8µmol/L) contributed independently to shorter overall survival (OS); whereas post-operative radiofrequency ablation and second resection independently improved OS in HCC. HCV-HCC had a more favorable prognosis than did HBV-HCC (Log-rank test, P

BackgroundAspartate transaminase/alanine transaminase (De Ritis) ratio is a good predictor of liver function damage, but its prognostic value in patients with hepatocellular carcinoma (HCC) undergoing hepatectomy remains unclear. This study aimed to assess the association of the De Ritis ratio with overall survival (OS) among hepatitis B virus (HBV)-related HCC patients undergoing hepatectomy.MethodsA total of 1,147 HCC patients were recruited. Cox regression analysis was used to identify the independent risk factors. Restricted cubic spline (RCS) was used to evaluate the association between the De Ritis ratio and mortality risk. Nomogram was constructed to determine the predictive power of the De Ritis ratio.ResultsMultivariate Cox regression analysis revealed that the tertile of the De Ritis ratio was an independent risk factor for mortality. After adjustment for confounding factors, the adjusted hazard ratios (HRs) with corresponding 95% CIs of mortality for the 2nd tertile and 3rd tertile were 1.175 (0.889–1.554) and 1.567 (1.199–2.046), respectively. RCS confirmed a non-linear association between the natural logarithm of the De Ritis ratio and the risk of mortality (p for non-linearity = 0.0375). The nomogram showed that the natural logarithm of the De Ritis ratio contributed the most to the prediction of prognosis in HBV-related HCC patients, and Harrell’s C-index was 0.680 with a 95% CI of 0.645–0.715.ConclusionThe De Ritis ratio is an independent predictor for OS in HBV-related HCC patients undergoing hepatectomy, which allows for prognostic stratification of patients, hence, individualized treatment and follow-up.

Abstract Background KRAS gene is the most common type of mutation reported in colorectal cancer (CRC). KRAS mutation-mediated regulation of immunophenotype and immune pathways in CRC remains to be elucidated. Methods 535 CRC patients were used to compare the expression of immune-related genes (IRGs) and the abundance of tumor-infiltrating immune cells (TIICs) in the tumor microenvironment between KRAS-mutant and KRAS wild-type CRC patients. An independent dataset included 566 cases of CRC and an in-house RNA sequencing dataset were served as validation sets. An in-house dataset consisting of 335 CRC patients were used to analyze systemic immune and inflammatory state in the presence of KRAS mutation. An immue risk (Imm-R) model consist of IRG and TIICs for prognostic prediction in KRAS-mutant CRC patients was established and validated. Results NF-κB and T-cell receptor signaling pathways were significantly inhibited in KRAS-mutant CRC patients. Regulatory T cells (Tregs) was increased while macrophage M1 and activated CD4 memory T cell was decreased in KRAS-mutant CRC. Prognosis correlated with enhanced Tregs, macrophage M1 and activated CD4 memory T cell and was validated. Serum levels of hypersensitive C-reactive protein (hs-CRP), CRP, and IgM were significantly decreased in KRAS-mutant compared to KRAS wild-type CRC patients. An immune risk model composed of VGF, RLN3, CT45A1 and TIICs signature classified CRC patients with distinct clinical outcomes. Conclusions KRAS mutation in CRC was associated with suppressed immune pathways and immune infiltration. The aberrant immune pathways and immune cells help to understand the tumor immune microenvironments in KRAS-mutant CRC patients.

Abstract A T4B hepatic flexure of colon cancer that had invaded the liver, gall bladder, and pancreas/duodenum was removed through a D3 expanded right hemicolectomy + pancreaticoduodenectomy +sectional VI and VII hepatic segmentectomy.

Abstract Purpose The overall survival (OS) of patients diagnosed with stage II‐III colorectal cancer (CRC) can vary greatly, even between patients with the same tumor stage. We aimed to design a nomogram to predict OS in resected, stage II‐III CRC and stratify patients with CRC into different risk groups. Patients and Methods Based on data from 873 patients with CRC, we used univariate Cox regression analysis to select the significant prognostic features, which were subjected to the least absolute shrinkage and selection operator (LASSO) regression algorithm for feature selection. Cross‐validation was used to confirm suitable tuning parameters (λ) for LASSO logistic regression. Then, the nomogram was used to estimate 3‐ and 5‐year OS based on the multivariable Cox regression model. The survival curves of the two groups were produced using the Kaplan‐Meier method. Risk group stratification was performed to assess the predictive capacity of the nomogram. Results Preoperative mean platelet volume, preoperative platelet distribution width, monocytes, and postoperative adjuvant chemotherapy were identified as independent prognostic factors by LASSO regression and integrated for the construction of the nomogram. The nomogram provided good discrimination, with C‐indices of 0.67 and 0.69 for the training and validation sets, respectively. Calibration plots illustrated excellent agreement between the nomogram predictions and actual observations for 3‐ and 5‐year OS. Moreover, a significant difference in OS was shown between patients stratified into different risk groups (P

Background: Inflammation and nutritional status are highly associated with colorectal cancer (CRC) prognosis. This study aimed to evaluate the prognostic value of the preoperative neutrophil-BMI ratio (NBR) in patients with CRC. Methods: A retrospective analysis was performed on 2471 patients with CRC who underwent surgical resection between 2004 and 2019. Patients were divided into two groups based on the cutoff value for NBR. Cox regression and Kaplan–Meier curves were used to evaluate overall survival (OS). Results: High NBR was associated with female sex, low BMI, colon, right-sided CRC, poor differentiation, T3 to 4 stage, M1 to 2 stage, high carcinoembryonic antigen (CEA) level, III-IV stage, microsatellite instability (MSI), and no adjuvant chemotherapy (all P

Colorectal carcinoma is a highly prevalent and heterogeneous gastrointestinal malignancy. The emergence of organoid technology has provided a new direction for colorectal cancer research. As a novel-type model, organoid has significant advantages compared with conventional tumor research models, characterized with the high success rate of construction and the high matching with the original tumor. These characteristics provide new possibilities to study the mechanism of colorectal carcinogenesis and improve the treatment effects. The present literature would mainly summarize the characteristics of tumor organoids and the up-to-date technique development of patient-derived organoids (PDOs) and application in colorectal cancer.

Background and Purpose: Systemic inflammation and nutritional status have been shown to be associated with the prognosis of colorectal cancer. The purpose of this study was to evaluate the impact of the serum C-reactive protein-to-body mass index ratio on the prognosis of patients with curatively resected colorectal cancer. Methods: We conducted a retrospective analysis of a database of 2,471 eligible patients with colorectal cancer who underwent curative resection at our hospital between 2004 and 2019. The optimal cut-off for CPR-to-BMI ratio was determined using maximally selected rank statistics. Patients were divided into 2 groups according to the cut-off value of the serum C-reactive protein-to-body mass index ratio. Kaplan-Meier curves and Cox regression analysis were used to compare overall survival. A two-sided P -value < 0.05 was considered statistically significant. Results: The proportion of patients with a high C-reactive protein-to-body mass index ratio increased with increasing age, male sex, right-sided colon cancer, poorly differentiated tumors, advanced-stage disease, local/distant metastases, tumor–node–metastasis stage, and microsatellite instability. In subgroup analysis according to tumor–node–metastasis stage, the overall survival of the high C-reactive protein-to-body mass index ratio group was significantly shorter than that of the low C-reactive protein-to-body mass index ratio group ( P < 0.001). Multivariate analysis identified age, differentiation, tumor–node–metastasis stage, carcinoembryonic antigen level, and the C-reactive protein-to-body mass index ratio as independent poor prognostic factors for overall survival. Conclusions: The C-reactive protein-to-body mass index ratio predicts the prognosis of patients with curatively resected colorectal cancer and is an independent risk factor for overall survival in patients with colorectal cancer.

PurposeThis study aimed to elucidate the prognostic significance of a novel inflammation-joined and nutrition-related clinicopathological marker for colorectal cancer (CRC).MethodsVarious factors from preoperative fasting blood samples from 2471 patients with CRC were retrospectively analyzed. Factors related to prognosis were evaluated using univariate and multivariate analyses. The Kaplan–Meier method was used to generate survival curves, while the log-rank test was used to measure survival differences between groups.ResultsUnivariate analysis revealed that C-reactive protein (CRP)/mean corpuscular volume (MCV) ratio, TNM stage, differentiation, right-sided tumor, age, carcinoembryonic antigen (CEA) level, and CRP level were significantly associated with poor prognosis in CRC. In contrast, adjuvant chemotherapy is regarded as a protective factor. Elevation of CRP/MCV ratio (odds ratio [OR]: 1.535, 95% confidence interval [CI]: 1.121–2.104, P = 0.008), TNM stage (OR: 2.747, 95% CI: 2.175–3.469, P < 0.001), and differentiation (OR, 1.384; 95% CI, 1.150–1.666; P = 0.001) were prognostic risk factors in the multivariate analyses. Subgroup analysis showed that CRP/MCV, TNM staging system, and differentiation also independently affected survival in patients with lymph node-positive CRC. The nomogram based on these three indicators showed that CRP/MCV had a greater prognostic value and clinical significance for lymph node-positive patients with poorly differentiated tumors at the late stage.ConclusionA novel nomogram using the clinicopathologic index of inflammation and nutrition was constructed to predict the prognosis of CRC. Early interventions should be emphasized for advanced-stage patients with severe inflammation and poor nutritional status.

BackgroundColorectal cancer (CRC) is estimated to be one of the most common cancers and the leading cause of cancer-related death worldwide. SOX9 is commonly overexpressed in CRC and participates in drug resistance. In addition, DNA damage repair confers resistance to anticancer drugs. However, the correlation between DNA damage repair and high SOX9 expression is still unclear. In this study, we aimed to investigate the function and the specific underlying mechanism of the SOX9-dependent DNA damage repair pathway in CRC.MethodsThe expression levels of SOX9 and MMS22L in CRC were examined by immunohistochemistry (IHC) and TCGA analysis. RNA sequencing was conducted in RKO SOX9-deficient cells and RKO shControl cells. Mechanistic studies were performed in CRC cells by modulating SOX9 and MMS22L expression, and we evaluated drug sensitivity and DNA damage repair signaling events. In addition, we investigated the effect of oxaliplatin in tumors with SOX9 overexpression and low expression of MMS22L in vivo.ResultsOur study showed that SOX9 has a higher expression level in CRC tissues than in normal tissues and predicts poor prognosis in CRC patients. Overexpression and knockdown of SOX9 were associated with the efficacy of oxaliplatin. In addition, SOX9 activity was enriched in the DNA damage repair pathway via regulation of MMS22L expression and participation in DNA double-strand break repair. SOX9 was upregulated and formed a complex with MMS22L, which promoted the nuclear translocation of MMS22L upon oxaliplatin treatment. Moreover, the xenograft assay results showed that oxaliplatin abrogated tumor growth from cells with MMS22L downregulation in mice.ConclusionsIn CRC, activation of the SOX9-MMS22L-dependent DNA damage pathway is a core pathway regulating oxaliplatin sensitivity. Targeting this pathway in oxaliplatin-resistant CRC cells is a promising therapeutic option.

BackgroundLymph node metastasis (LNM) is a well-established prognostic factor for colon cancer. Preoperative LNM evaluation is relevant for planning colon cancer treatment. The aim of this study was to construct and evaluate a nomogram for predicting LNM in primary colon cancer according to pathological features.Patients and MethodsSix-hundred patients with clinicopathologically confirmed colon cancer (481 cases in the training set and 119 cases in the validation set) were enrolled in the Affiliated Cancer Hospital of Guangxi Medical University from January 2010 to December 2019. The expression of molecular markers (p53 and β-catenin) was determined by immunohistochemistry. Multivariate logistic regression was used to screen out independent risk factors, and a nomogram was established. The accuracy and discriminability of the nomogram were evaluated by consistency index and calibration curve.ResultsUnivariate logistic analysis revealed that LNM in colon cancer is significantly correlated (P

Purpose: Vascular invasion (VI) is associated with recurrence and is an indicator of poor prognosis in gastric cancer (GC). Pre-operative identification of VI may guide the selection of the optimal surgical approach and assess the requirement for neoadjuvant therapy. Methods: A total of 271 patients were retrospectively collected and randomly allocated into the training and validation datasets. The least absolute shrinkage and selection operator regression model was used to select potentially relevant features, and multivariable logistic regression analysis was used to develop the nomogram. Results: The nomogram consisted of pre-operative serum complement C3 levels, duration of symptoms, pre-operative computed tomography stage, abdominal distension and undifferentiated carcinoma. The nomogram provided good calibration for both the training and the validation set, with area under the curve values of 0.792 and 0.774. Decision curve analysis revealed that the nomogram was clinically useful. Conclusion: The present study constructed a nomogram for the pre-operative prediction of VI in patients with GC. The nomogram may aid the identification of high-risk patients and aid the optimization of pre-operative decision-making.

BackgroundTumor mutational burden (TMB) could be a measure of response to immune checkpoint inhibitors therapy for patients with colorectal cancer (CRC). MicroRNAs (miRNAs) participate in anticancer immune responses. In the present study, we determined miRNA expression patterns in patients with CRC and built a signature that predicts TMB.MethodsNext generation sequencing (NGS) on formalin-fixed paraffin-embedded samples from CRC patients was performed to measure TMB levels. We used datasets from The Cancer Genome Atlas to compare miRNA expression patterns in samples with high and low TMB from patients with CRC. We created an miRNA-based signature index using the selection operator (LASSO) and least absolute shrinkage method from the training set. We used an independent test set as internal validation. We used real-time polymerase chain reaction (RT-PCR) to validate the miRNA-based signature classifier.ResultsTwenty-seven samples from CRC patients underwent NGS to determine the TMB level. We identified four miRNA candidates in the training set for predicting TMB (N = 311). We used the test set (N = 204) for internal validation. The four-miRNA-based signature classifier was an accurate predictor of TMB, with accuracy 0.963 in the training set. In the test set, it was 0.902; and it was 0.946 in the total set. The classifier was superior to microsatellite instability (MSI) for predicting TMB in TCGA dataset. In the validation cohort, MSI status more positively correlated with TMB levels than did the classifier. Validation from RT-qPCR showed good target discrimination of the classifier for TMB prediction.ConclusionTo our knowledge, this is the first miRNA-based signature classifier validated using high quality clinical data to accurately predict TMB level in patients with CRC.

BackgroundEpithelial mesenchymal transformation (EMT) and DNA repair status represent intrinsic features of colorectal cancer (CRC) and are associated with patient prognosis and treatment responsiveness. We sought to develop a combined EMT and DNA repair gene panel with potential application in patient classification and precise treatment.MethodsWe comprehensively evaluated the EMT and DNA repair patterns of 1,652 CRC patients from four datasets. Unsupervised clustering was used for classification. The clinical features, genetic mutation, tumor mutation load, and chemotherapy as well as immunotherapy sensitivity among different clusters were systematically compared. The least absolute shrinkage and selection operator regression method was used to develop the risk model.ResultsThree distinct CRC clusters were determined. Clustet1 was characterized by down-regulated DNA repair pathways but active epithelial markers and metabolism pathway and had intermediate prognosis. Clustet2 was characterized by down-regulated both epithelial markers and DNA repair pathways and had poor outcome. Clustet3 presented with activation of DNA repair pathway and epithelial markers had favorable prognosis. Clustet1 might benefit form chemotherapy and Clustet3 had a higher response rate to immunotherapy. An EMT and DNA repair risk model related to prognosis and treatment response was developed.ConclusionsThis work developed and validated a combined EMT and DNA repair gene panel for CRC classification, which may be an effective tool for survival prediction and treatment guidance in CRC patients.

In order to promote the industrialization of the large deformation technology of carbon fiber composites, this paper studies a new method of forming of helical carbon fiber reinforced aluminum matrix composite. The purpose is to solve the problem of large deformation of carbon fiber with low elongation and metal matrix with high elongation. By introducing carbon fiber with helical space structure into the aluminum matrix, the helical carbon fiber reinforced aluminum matrix composites were prepared and the subsequent drawing deformation was carried out. Here we systematically studied the large plastic deformation behavior of helical carbon fiber reinforced aluminum matrix composite via a combination of numerical simulations and experiments, and analyzed the deformation law and stress of helical carbon fiber in the deformation process. We found that the plastic deformation of the composite causes local stress concentration around the helical carbon fiber, and the helical carbon fiber will move synchronously with the aluminum matrix during the deformation, and receive the pressure from the aluminum matrix. Second, the best process parameters obtained from the simulation, that is, the drawing die angle α = 7°, when five-pass drawing experiments were carried out, the total deformation reached 58%, and the average elongation of a single pass was 18.9%. The experimental show carbon fiber reinforced aluminum matrix composite with helical space structure can achieve large deformation and high strength. The experimental and simulation are in general agreement, which verifies the correctness of the carbon fiber helical structure model.

Purpose Gastric cancer (GC) has a poor prognosis and high rate of recurrence. Perineural invasion (PNI) is a prognostic factor in GC that is associated with a high risk of systemic recurrence. Preoperative identification of PNI may facilitate patient stratification and optimal preoperative treatment. We therefore developed and validated a nomogram for the preoperative prediction of PNI. Methods We retrospectively collected clinical data from 261 GC patients, who were randomly assigned to training (n = 185) and validation (n = 76) sets. The least absolute shrinkage and selection operator regression model was used to identify potentially relevant clinical parameters, and multivariable logistic regression analysis was used to develop the nomogram. Results The nomogram consisted of body mass index, immunoglobulin A level, and computed tomography-based T- and N-stages. Good calibration was observed for both the training and validation sets, with areas under the curve of 0.77 and 0.79, respectively. Decision curve analysis revealed that the nomogram was clinically relevant. Conclusion We developed and validated a nomogram for the preoperative prediction of PNI in patients with GC. Our nomogram may facilitate the identification of high-risk patients and optimization of preoperative decision-making.

Fluoropyrimidine-based chemotherapy is an essential component of systemic chemotherapy for colorectal cancer (CRC). The immune response is implicated in chemotherapy-induced cytotoxicity. Here, we reported an immune risk (Imm-R) model for prognostic prediction in patients receiving fluoropyrimidine-based chemotherapy. Gene expression profiles and corresponding clinical information were collected from four data sets and divided into training set (n = 183) and validation set (validation set1: n = 34; validation set2: n = 99). The composition of 22 tumor-infiltrating immune cells (TIICs) populations was characterized with the CIBERSORT deconvolution algorithm. A prognostic Imm-R model for predicting overall survival was established by performing least absolute shrinkage and selection operator (LASSO) penalized COX regression analysis. T follicular helper cells and M0 macrophages were associated with better survival, while eosinophils were associated with worse survival. TIICs signature was constructed based on the above three immune cell types. Furthermore, a Imm-R model was created by integrating TIICs signature with immune-related genes (IRGs), which effectively in distinguishing CRC patients with poorer prognosis. The Imm-R model was associated with activation of the TGF-beta signaling and suppression of DNA damage. Results of this research provide new insights into the role of immunity for in fluoropyrimidine-based chemotherapy as well as a useful tools to predict the outcome of CRC patients receiving fluoropyrimidine-based chemotherapy.

Carbon fiber is mainly distributed in the shape of short fibers and continuous fiber bundles as the reinforcing phase in metal matrix composites, and it is seldom studied as braided rope shaped to reinforce the matrix. For this paper, the pretreatment and the surface metallization of the carbon fiber braided rope were studied. Besides, the casting experiments of aluminum-based carbon fiber braided rope composites were performed without external pressure. XPS analysis shows that the surface of the carbon fiber braided rope treated with ultrasonic degumming contains many hydrophilic oxygen-containing functional groups C-OH, C=O, COOH, etc., which can effectively improve the wettability between the carbon fiber braided rope and the aluminum matrix. SEM, EDS, and XRD were used to analyze the micromorphology and structure of the copper plating on the surface of carbon fiber braided ropes obtained from different pH plating solutions. When pH is 12, a continuous, uniform, and dense layer was formed on the surface of carbon fiber braided ropes. In addition, copper coating can effectively inhibit the formation of Al4C3 brittle phase. Finally, the mechanical properties results indicated that the tensile strength of the carbon fiber bundle and carbon fiber rope reinforced composite materials were 69 MPa and 83 MPa, respectively, indicating that the reinforcing effect of the carbon fiber rope is better than that of the carbon fiber bundle.

Biphasic calcium phosphate (BCP) ceramics, viewed as the first-line therapeutic materials in clinical practice, are still confronted with challenges such as undesirable biocompatibility and bioactivity given their structural and chemical deficiency. In this study, we designed a novel microporous ${{{\rm{CO}}}_{{\rm{3}}}}^{{\rm{2}}-}$ -containing BCP ceramic from Salmo salar bone in a CO _2 atmosphere via two-step high-temperature sintering, and its physicochemical properties and biocompatibility were explored. A without ${{{\rm{CO}}}_{{\rm{3}}}}^{{\rm{2}}-}$ - BCP bioceramic material prepared in a single gas atmosphere was used as a comparison. The two scaffolds were characterized by x-ray diffraction (XRD), fourier transform infrared (FTIR) spectroscopy, and scanning electron microscopy (SEM) , measured the size of its porosity and specific surface area by an instrument and in vitro cell experiment was used to test its biocompatibility. Such synthetic strategy endowed the BCP products with increased β -tricalcium phosphate ( β -TCP) percentage from 37.18wt% to 45.3wt% (compared to BCP without ${{{\rm{CO}}}_{{\rm{3}}}}^{{\rm{2}}-}$ ), with the ${{{\rm{CO}}}_{{\rm{3}}}}^{{\rm{2}}-}$ content calculated to be 1.98wt%, which is close to that in human bone tissue. The amount of ${{{\rm{CO}}}_{{\rm{3}}}}^{{\rm{2}}-}$ incorporation, the a-axes of the lattice parameters have decreased significantly from 9.4845 nm to 9.2942 nm by Rietveld structure refinement. Especially, the novel ${{{\rm{CO}}}_{{\rm{3}}}}^{{\rm{2}}-}$ containing BCP exhibits a lower degree of crystallinity than that without CO3 ^2- . In addition, the natural microporosity remarkably increased from 49.6% for BCP without ${{{\rm{CO}}}_{{\rm{3}}}}^{{\rm{2}}-}$ to 64.06% for ${{{\rm{CO}}}_{{\rm{3}}}}^{{\rm{2}}-}$ -containing BCP, and the specific surface area increased from 5.829 m ^2 g ^−1 to 17.161 m ^2 g ^−1 . Besides, two materials were non-toxic to human bone marrow mesenchymal stem cells (hBMSCs), and the ${{{\rm{CO}}}_{{\rm{3}}}}^{{\rm{2}}-}$ -containing BCP had more factor expression in the early stage of osteogenesis induction, such as Runx2 and Smad 4. Overall, microporous ${{{\rm{CO}}}_{{\rm{3}}}}^{{\rm{2}}-}$ -containing BCP were prepared via a simple preparation method from natural bone, combining the structural and chemical preponderance, as well as in vitro performance it should be considered as a promising biomaterial for further explorations in the fields of bone graft materials from natural bone to satisfy versatile clinical requirements.

Bone morphogenetic protein-9 (BMP9) shows great osteoinductive potential in bone regeneration. Periodontal ligament stem cells (PDLSCs) with multi-differentiation capability and low immunogenicity are increasingly used as seed cells for periodontal regenerative therapies. In the present study, we investigated the potent osteogenic activity of BMP9 on human PDLSCs (hPDLSCs), in which the c-Jun N-terminal kinase (JNK) pathway is possibly involved. Our results showed that JNK inhibition by the specific inhibitor SP600125 or adenovirus expressing small interfering RNA (siRNA) targeting JNK (AdR-si-JNK) significantly decreased BMP9-induced gene and protein expression of early and late osteogenic markers, such as runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), osteopontin (OPN), and osteocalcin (OCN), in hPDLSCs. We also confirmed the in-vivo positive effect of JNKs on ectopic bone formation induced by hPDLSCs injected into the musculature of athymic nude mice and BMP9 ex vivo gene delivery. For the cellular mechanism, we found that BMP9 activated the phosphorylation of JNKs and Smad2/3, and that JNKs may engage in cross-talk with the Smad2/3 pathway in BMP9-mediated osteogenesis.

To explore why some oligonucleotides in denaturing polyacrylamide gel could not be silver-stained, 134 different oligonucleotides were analyzed using denaturing polyacrylamide gel electrophoresis stained with silver and asymmetric cyanine. As a result, we found that the sensitivity of oligos (dA), (dC), (dG) and (dT) to silver staining could be ranged as (dA) > (dG) > (dC) > (dT) from high to low. It was unexpected that oligo (dT) was hard to be silver-stained. Moreover, the silver staining of an oligonucleotide containing base T could be partially or completely inhibited by base T. The inhibition of silver staining by base T was a competitive inhibition which could be affected by the amounts of the argyrophil nucleobase and base T, the cis-distance between the argyrophil nucleobase and base T, and the gel concentration. The changes of the intensity of an oligonucleotide band caused by the changes of DNA base composition were diverse and interesting. The intensity of some oligonucleotide bands would significantly change when the changes of DNA base composition accumulated to a certain extent (usually ≥ 4 nt). The sensitivity of cyanine staining of ≤ 11-nt long oligonucleotides could be enhanced about 250-fold by fixing the gels with methanol fixing solution.

OBJECTIVE: Caspase-8 (CASP8) plays a central role in the apoptotic pathway and aberrant regulation of this pathway may cause cancers. Previous studies investigating the association between CASP8 -652 6N ins/del polymorphism and colorectal cancer (CRC) risk showed inconclusive results. We performed a meta-analysis of all available studies to investigate this association. METHODS: All studies published up to October 2013 on the association between CASP8 -652 6N ins/del polymorphism and CRC risk were identified by searching electronic databases PubMed, EMBASE, and Cochrane library. The association between CASP8 -652 6N ins/del polymorphism and CRC risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs). RESULTS: Six studies with 6,325 cases and 6,842 controls were included in the meta-analysis. We observed that the CASP8 -652 6N ins/del polymorphism was significantly correlated with CRC risk when all studies were pooled into the meta-analysis (ins/del vs. ins/ins: OR = 0.890, 95%CI 0.821-0.964, P = 0.004; del/del + ins/del vs. ins/ins: OR = 0.899, 95%CI 0.833-0.970, P = 0.006). In stratified analyses by ethnicity, source of control, and quality score, significant association was observed in Asians (ins/del vs. ins/ins: OR = 0.862, 95%CI 0.761-0.977, P = 0.020; del/del + ins/del vs. ins/ins: OR = 0.845, 95%CI 0.749-0.953, P = 0.006), population-based studies (ins/del vs. ins/ins: OR = 0.890, 95%CI 0.813-0.975, P = 0.012; del/del + ins/del vs. ins/ins: OR = 0.901, 95%CI 0.827-0.982, P = 0.018), and high quality studies. However, in subgroup analysis according to cancer location, no significant association was detected. CONCLUSIONS: The present meta-analysis suggests that the CASP8 is a candidate gene for CRC susceptibility. The CASP8 -652 6N ins/del polymorphism may play a protective role in CRC development especially among Asians. Further large and well-designed studies are needed to confirm this association.

BACKGROUND: Serum carcinoembryonic antigen (sCEA) level might be an indicator of disease. Indeed, an elevated sCEA level is a prognostic factor in colorectal cancer (CRC) patients. However, the genetic determinants of sCEA level in healthy and CRC population remains unclear. Thus we investigated the genetic markers associated with elevated serum sCEA level in these two populations and its clinical implications. METHODS AND FINDINGS: Genome-wide association study (GWAS) was conducted in a cohort study with 4,346 healthy male adults using the Illumina Omni 1 M chip. Candidate SNPs associated with elevated sCEA levels were validated in 194 CRC patients on ABI Taqman platform. Eight candidate SNPs were validated in CRC patients. The rs1047781 (chr19- FUT2) (A/T) was associated with elevated sCEA levels, and rs8176746 (chr9- ABO) was associated with the regional lymph metastasis in the CRC patients. The preoperative sCEA level was a risk factor for tumor recurrence in 5 years after operation (OR = 1.427, 95% CI: 1.005∼1.843, P = 0.006). It was also one of the risk factors for regional lymph node metastasis (OR = 2.266, 95% CI: 1.196∼4.293, P = 0.012). The sCEA level in rs1047781-T carriers was higher than that in the A carriers in CRC patients without lymph node metastasis (P = 0.006). The regional lymph node metastasis in patients with homozygote AA of rs8176746 was more common than that in the heterozygote AG carriers (P = 0.022). In addition, rs1047781-AT and TT CRC patients exhibited a worse disease-free survival than AA genotype carriers (P = 0.023). CONCLUSIONS: We found candidate SNPs associated with elevated sCEA levels in both healthy males and CRC population. Rs1047781 (chr19- FUT2) may be the susceptible locus for recurrence of CRC in a population from Southern China.

OBJECTIVE: Cyclooxygenase-2 (COX-2) is an inducible enzyme converting arachidonic acid to prostaglandins and playing important roles in inflammatory diseases as well as tumor development. Previous studies investigating the association between COX-2 polymorphisms and colorectal cancer (CRC) risk reported conflicting results. We performed a meta-analysis of all available studies to explore this association. METHODS: All studies published up to October 2013 on the association between COX-2 polymorphisms and CRC risk were identified by searching electronic databases PubMed, EMBASE, and Cochrane library. The association between COX-2 polymorphisms and CRC risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs). RESULTS: Ten studies with 6,774 cases and 9,772 controls were included for -1195A>G polymorphism, 13 studies including 6,807 cases and 10,052 controls were available for -765G>C polymorphism, and 8 studies containing 5,121 cases and 7,487 controls were included for 8473T>C polymorphism. With respect to -765G>C polymorphism, we did not find a significant association with CRC risk when all eligible studies were pooled into the meta-analysis. However, in subgroup analyses by ethnicity and cancer location, with a Bonferroni corrected alpha of 0.05/2, statistical significant increased CRC risk was found in the Asian populations (dominant model CC+CG vs. GG: OR = 1.399, 95%CI: 1.113-1.760, P = 0.004) and rectum cancer patients (CC vs. GG: OR = 2.270, 95%CI: 1.295-3.980, P = 0.004; Recessive model CC vs. CG+GG: OR = 2.269, 95%CI: 1.297-3.970, P = 0.004). In subgroup analysis according to source of control, no significant association was detected. With respect to -1195A>G and 8473T>C polymorphisms, no significant association with CRC risk was demonstrated in the overall and subgroup analyses. CONCLUSIONS: The present meta-analysis suggests that the COX-2 -765G>C polymorphism may be a risk factor for CRC in Asians and rectum cancer patients. Further large and well-designed studies are needed to confirm this association.

The mouse double minute 2 (MDM2) gene encodes a phosphoprotein that interacts with P53 and negatively regulates its activity. The SNP309 polymorphism (T-G) in the promoter of MDM2 gene has been reported to be associated with enhanced MDM2 expression and tumor development. Studies investigating the association between MDM2 SNP309 polymorphism and colorectal cancer (CRC) risk reported conflicting results. We performed a meta-analysis of all available studies to explore the association of this polymorphism with CRC risk.All studies published up to July 2013 on the association between MDM2 SNP309 polymorphism and CRC risk were identified by searching electronic databases PubMed, EMBASE, and Chinese Biomedical Literature database (CBM) databases. The association between the MDM2 SNP309 polymorphism and CRC risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs).A total of 14 case-control studies including 4460 CRC cases and 4828 controls were identified. We did not find a significant association between the MDM2 SNP309 polymorphism and CRC risk in all genetic models in overall population. However, in subgroup analysis by ethnicity, significant associations were found in Asians (TG vs. TT: OR = 1.197, 95% CI = 1.055-1.358, P=0.005; GG+TG vs. TT: OR = 1.246, 95% CI = 1.106-1.404, P=0.000) and Africans. When stratified by HWE in controls, significantly increased risk was also found among the studies consistent with HWE (TG vs. TT: OR = 1.166, 95% CI = 1.037-1.311, P= 0.010). In subgroup analysis according to p53 mutation status, and gender, no any significant association was detected.The present meta-analysis suggests that the MDM2 is a candidate gene for CRC susceptibility. The MDM2 SNP309 polymorphism may be a risk factor for CRC in Asians.