Multicenter validation of an artificial intelligence (AI)-based platform for the diagnosis of acute appendicitis.

BACKGROUND: The current scores used to help diagnose acute appendicitis have a "gray" zone in which the diagnosis is usually inconclusive. Furthermore, the universal use of CT scanning is limited because of the radiation hazards and/or limited resources. Hence, it is imperative to have an accurate diagnostic tool to avoid unnecessary, negative appendectomies. METHODS: This was an international, multicenter, retrospective cohort study. The diagnostic accuracy of the artificial intelligence platform was assessed by sensitivity, specificity, negative predictive value, the area under the receiver curve, precision curve, F1 score, and Matthews correlation coefficient. Moreover, calibration curve, decision curve analysis, and clinical impact curve analysis were used to assess the clinical utility of the artificial intelligence platform. The accuracy of the artificial intelligence platform was also compared to that of CT scanning. RESULTS: Two data sets were used to assess the artificial intelligence platform: a multicenter real data set (n = 2,579) and a well-qualified synthetic data set (n = 9736). The platform showed a sensitivity of 92.2%, specificity of 97.2%, and negative predictive value of 98.7%. The artificial intelligence had good area under the receiver curve, precision, F1 score, and Matthews correlation coefficient (0.97, 86.7, 0.89, 0.88, respectively). Compared to CT scanning, the artificial intelligence platform had a better area under the receiver curve (0.92 vs 0.76), specificity (90.9 vs 53.3), precision (99.8 vs 98.9), and Matthews correlation coefficient (0.77 vs 0.72), comparable sensitivity (99.2 vs 100), and lower negative predictive value (67.6 vs 99.5). Decision curve analysis and clinical impact curve analysis intuitively revealed that the platform had a substantial net benefit within a realistic probability range from 6% to 96%. CONCLUSION: The current artificial intelligence platform had excellent sensitivity, specificity, and accuracy exceeding 90% and may help clinicians in decision making on patients with suspected acute appendicitis, particularly when access to CT scanning is limited.

Bergaptol inhibits glioma cell proliferation and induces apoptosis via STAT3/Bcl-2 pathway.

Glioblastoma (GBM) is the most common primary malignant brain tumour and lacks therapeutic options with significant effects. The aberrant activation of STAT3 is a critical factor in glioma progression via activating multiple signalling pathways that promote glioma. Among them, the antiapoptotic gene Bcl-2 could be upregulated by p-STAT3, which is an important reason for the continuous proliferation of glioma. We previously reported that bergaptol, a natural furanocoumarin widely found in citrus products, exerts antineuroinflammatory effects by inhibiting the overactivation of STAT3. Here, we aimed to evaluate whether bergaptol could promote glioma apoptosis by inhibiting the STAT3/Bcl-2 pathway. This study found that bergaptol inhibited the proliferation and migration of GBM cell lines (U87 and A172) and promoted apoptosis in vitro. We also found that bergaptol significantly inhibited the STAT3/Bcl-2 pathway in GBM cells. U87 cells were implanted intracranially into nude mice to establish a glioma model, and glioma-bearing mice were treated with bergaptol (40 mg/kg). Bergaptol treatment significantly inhibited glioma growth and prolonged the glioma-bearing mice's survival time. In addition, bergaptol administration also significantly inhibited the STAT3/Bcl-2 pathway of tumour tissue in vivo. Overall, we found that bergaptol could effectively play an antiglioma role by inhibiting STAT3/Bcl-2 pathway, suggesting the potential efficacy of bergaptol in treating glioma.

Comparison of the effect between traditional conservation and nasointestinal tube placement in adhesive small bowel obstruction: A matched case-control study.

Adhesive small bowel obstruction (ASBO) causes a major burden in emergency medicine. Owing to in situ decompression, nasointestinal tube (NIT) placement has been increasingly used in clinical practice compared with traditional conservation (TC); however, the indications remain controversial. This study was designed to explore the indications for each treatment in ASBOs and then suggest the optimal strategy. After propensity score matching, 128 pairs were included (the NIT and TC groups). The occurrence of severe adverse events (SAEs), peri-treatment clinical parameters, and radiological features were compared between the successful and failed treatment groups. According to different stages of the entire treatment, the independent risk factors for adverse effects for ASBO were analysed in phase I and phase II. In phase I, normal red blood cells (RBC) levels (p = 0.011) and a balanced sodium ion level (p = 0.016) positively affected the outcomes of TC treatment. In phase II, for the TC group, the successful treatment rate reached 79.5% for patients with ASBOs whose normal RBC levels (p = 0.006) or decreasing white blood cells (WBC) levels (p = 0.014) after treatment. For the NIT group, the treatment success rate was 68.1% for patients whose electrolyte imbalance could be reversed or whose neutrophil count/lymphocyte ratio (NLR) levels was lower than 4.3 (p = 0.018). TC treatment is highly recommended for patients with normal RBC counts and sodium levels pretreatment. After dynamic monitoring of the treatment process, for both the TC and NIT groups, once ASBOs had elevated inflammatory biomarkers or irreversible electrolyte disturbances, surgical interference was preferred.

Prediction of injury localization in preoperative patients with gastrointestinal perforation: a multiomics model analysis.

BACKGROUND: The location of gastrointestinal perforation is essential for severity evaluation and optimizing the treatment approach. We aimed to retrospectively analyze the clinical characteristics, laboratory parameters, and imaging features of patients with gastrointestinal perforation and construct a predictive model to distinguish the location of upper and lower gastrointestinal perforation. METHODS: A total of 367 patients with gastrointestinal perforation admitted to the department of emergency surgery in Fujian Medical University Union Hospital between March 2014 and December 2020 were collected. Patients were randomly divided into training set and test set in a ratio of 7:3 to establish and verify the prediction model by logistic regression. The receiver operating characteristic curve, calibration map, and clinical decision curve were used to evaluate the discrimination, calibration, and clinical applicability of the prediction model, respectively. The multiomics model was validated by stratification analysis in the prediction of severity and prognosis of patients with gastrointestinal perforation. RESULTS: The following variables were identified as independent predictors in lower gastrointestinal perforation: monocyte absolute value, mean platelet volume, albumin, fibrinogen, pain duration, rebound tenderness, free air in peritoneal cavity by univariate logistic regression analysis and stepwise regression analysis. The area under the receiver operating characteristic curve of the prediction model was 0.886 (95% confidence interval, 0.840-0.933). The calibration curve shows that the prediction accuracy and the calibration ability of the prediction model are effective. Meanwhile, the decision curve results show that the net benefits of the training and test sets are greater than those of the two extreme models as the threshold probability is 20-100%. The multiomics model score can be calculated via nomogram. The higher the stratification of risk score array, the higher the number of transferred patients who were admitted to the intensive care unit (P < 0.001). CONCLUSION: The developed multiomics model including monocyte absolute value, mean platelet volume, albumin, fibrinogen, pain duration, rebound tenderness, and free air in the peritoneal cavity has good discrimination and calibration. This model can assist surgeons in distinguishing between upper and lower gastrointestinal perforation and to assess the severity of the condition.

Cysteine-modified PEGylated nanoparticles for targeted delivery of methylprednisolone to pancreatitis.

The timely suppression of inflammatory mediator production and mitigation of their effects on pancreatic acinar cells are crucial for the successful management of acute pancreatitis. To achieve effective treatment, we present a novel approach utilizing cysteine modified PEG nanoparticles for both precise accumulation at the site of pancreatitis and specific targeting of acinar cells. Methylprednisolone, a nonsteroidal anti-inflammatory drug, was tailored to enhance its circulation time in the bloodstream, preferentially accumulate in the pancreas and enhance cell uptake efficiency by acinar cells through specifically targeting L-Type amino acid transporter 1. The nanosystem significantly downregulated pro-inflammatory cytokines in plasma, resulting in the effective suppression of inflammation in acinar cells within an acute pancreatitis rat model. The utilization of the dual targeted therapy strategy holds considerable potential for the clinical management of pancreatitis.

Accuracy and applicability of the novel pneumoperitoneum three-dimensional volume rendering technique in adhesive small bowel obstruction.

Background: The accurate diagnosis of adhesive small bowel obstruction (ASBO) is challenging for surgeons. The aim of this study was to demonstrate that pneumoperitoneum 3-dimensional volume rendering (3DVR) can provide an accurate diagnosis and has applicability in ASBO. Methods: In this retrospective study, patients who underwent preoperative pneumoperitoneum 3DVR and surgery for ASBO between October 2021 and May 2022 were enrolled. The surgical findings were taken as the gold standard, and the kappa test was used to verify the consistency of the pneumoperitoneum 3DVR results and surgical findings. Results: A total of 22 patients with ASBO were included in this study, 27 sites of obstruction adhesions were found during surgery, and 5 patients had both parietal adhesions and interintestinal adhesions. Sixteen parietal adhesions (16/16) were found using pneumoperitoneum 3DVR (κ=1.00; P<0.001), and the diagnosis of parietal adhesions on pneumoperitoneum 3DVR was perfectly consistent with the surgical findings. Eight (8/11) interintestinal adhesions were found using pneumoperitoneum 3DVR (κ=0.727; P<0.001), and the diagnosis of interintestinal adhesions on pneumoperitoneum 3DVR was substantially consistent with the surgical findings. Conclusions: The novel pneumoperitoneum 3DVR is accurate and applicable in ASBO. It can help personalize the treatment of patients and can be useful in planning a more effective surgical approach.

Radiomics approach with deep learning for predicting T4 obstructive colorectal cancer using CT image.

OBJECTIVES: Patients with T4 obstructive colorectal cancer (OCC) have a high mortality rate. Therefore, an accurate distinction between T4 and T1-T3 (NT4) in OCC is an important part of preoperative evaluation, especially in the emergency setting. This paper introduces three models of radiomics, deep learning, and deep learning-based radiomics to identify T4 OCC. METHODS: We established a dataset of computed tomography (CT) images of 164 patients with pathologically confirmed OCC, from which 2537 slides were extracted. First, since T4 tumors penetrate the bowel wall and involve adjacent organs, we explored whether the peritumoral region contributes to the assessment of T4 OCC. Furthermore, we visualized the radiomics and deep learning features using the t-distributed stochastic neighbor embedding technique (t-SNE). Finally, we built a merged model by fusing radiomic features with deep learning features. In this experiment, the performance of each model was evaluated by the area under the receiver operating characteristic curve (AUC). RESULTS: In the test cohort, the AUC values predicted by the radiomics model in the dilated region of interest (dROI) was 0.770. And the AUC value of the deep learning model with the patches extended 20-pixel reached 0.936. Combining the characteristics of radiomics and deep learning, our method achieved an AUC value of 0.947 in the T4 and non-T4 (NT4) classification, and increased the AUC value to 0.950 after the addition of clinical features. CONCLUSION: The prediction results of our merged model of deep learning radiomics outperformed the deep learning model and significantly outperformed the radiomics model. The experimental results demonstrate that combining the peritumoral region improves the prediction performance of the radiomics model and the deep learning model.

Resistance-driven innovations in the discovery of bactericides: novel triclosan derivatives decorating isopropanolamine moiety as promising anti-biofilm agents against destructive plant bacterial diseases.

BACKGROUND: Controlling bacterial infections in plants is a major challenge owing to the appearance of resistant strains. As a physical barrier, the bacterial biofilm helps bacterial infections acquire drug resistance by enabling bacteria to accommodate complex and volatile environmental conditions and avoid bactericidal effects. Thus, developing new antibacterial agents with antibiofilm potency is imperative. RESULTS: A series of simple triclosan derivatives containing isopropanolamine moiety were elaborately designed and assessed for their antibacterial behavior. Bioassay results showed that some title compounds had excellent bioactivity against three destructive bacteria Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas axonopodis pv. citri (Xac) and Pseudomonas syringae pv. actinidiae (Psa). Notably, compound C8 displayed high bioactivities toward Xoo and Xac, with EC50 values were 0.34 and 2.11 µg mL-1 , respectively. In vivo trials revealed that compound C8 exhibited excellent protective activities against rice bacterial blight and citrus bacterial canker at 200 µg mL-1 , with control effectivenesses of 49.57% and 85.60%, respectively. Compound A4 had remarkably inhibitory activity toward Psa, with an EC50 value of 2.63 µg mL-1 , and demonstrated outstanding protective activity with a value of 77.23% against Psa in vivo. Antibacterial mechanisms indicated that compound C8 dose-dependently prevented biofilm formation and extracellular polysaccharide production. C8 also significantly weakened the motility and pathogenicity of Xoo. CONCLUSION: This study contributes to the development and excavation of novel bactericidal candidates with broad-spectrum antibacterial activity by targeting bacterial biofilm to control refractory plant bacterial diseases. © 2023 Society of Chemical Industry.

Comparison between Clinical Utility of CXCL-8 and Clinical Practice Tumor Markers for Colorectal Cancer Diagnosis.

Owing to the high incidence and mortality rates of colorectal cancer (CRC), novel biomarkers for CRC diagnosis are critically needed. Therefore, this study is aimed at exploring the clinical utility of serum C-X-C motif chemokine 8 (CXCL-8) for CRC diagnosis and progression compared to the routinely used biomarkers, carcinoembryonic antigen (CEA), and carbohydrate antigen-19-9 (CA19-9). This study included 227 patients with CRC, 110 patients with colorectal adenoma (CA), and 123 healthy participants, who were recruited from the Fujian Medical University Union Hospital from July 1, 2019 to October 31, 2020. Serum concentrations of CXCL-8, CEA, and CA19-9 were detected using enzyme-linked immunosorbent assay and chemiluminescent microparticle immunoassay. Clinicopathological features of patients with CRC were collected and analyzed. The diagnostic efficacy of CXCL-8, CEA, and CA19-9 for CRC was evaluated using receiver operating characteristic (ROC) curves. We found that the serum concentrations of CXCL-8, CEA, and CA19-9 were significantly higher in patients with CRC than those in patients with CA and healthy controls. The diagnostic sensitivity of CXCL-8 alone was higher than those of CEA and CA19-9 both and when combined; thus, CXCL-8 may be better at discriminating patients with CRC from healthy controls and patients with CA. Moreover, combining CXCL-8 with CEA or CA19-9 improved their respective diagnostic performances in distinguishing patients with CRC from CA patients and healthy participants. Notably, we also found that serum concentrations of CXCL-8 were positively correlated with metastases and tumor size. Therefore, our study suggests that serum CXCL-8 may serve as an improved biomarker for CRC diagnosis compared to the traditional tumor markers CEA and CA19-9. Moreover, our findings indicate the potential efficacy of serum CXCL-8 levels as a CRC prognostic biomarker.

Methylated Septin 9 as a Promising Biomarker in the Diagnosis and Recurrence Monitoring of Colorectal Cancer.

Purpose: The clinical utility of plasma methylated septin 9 (mSEPT9) DNA in screening and recurrence monitoring for colorectal cancer (CRC) is highly promising. The present study was performed to determine the diagnostic value of mSEPT9 in CRC detection and recurrence monitoring in Chinese patients. Methods: Overall, 616 patients newly diagnosed with CRC and 122 individuals with no evidence of disease were recruited from October 1, 2019, to May 31, 2021, at Fujian Medical University Union Hospital. Plasma and serum samples were collected for analyzing mSEPT9, carcinoembryonic antigen (CEA), and carbohydrate antigen-19-9 (CA19-9). Data on clinicopathological characteristics were collected and analyzed. Sensitivity and specificity were calculated to evaluate the diagnostic potential of each marker; the receiver operating characteristic (ROC) curve was applied for the assessment of diagnostic value, and comparisons among mSEPT9, CEA, CA19-9, and their combination were assessed via ROC curves. Results: mSEPT9 achieved an overall sensitivity and specificity of 72.94% and 81.97%, respectively, with an area under the curve (AUC) value of 0.826, which were higher than those of CEA (sensitivity: 43.96%; specificity: 96.72%; AUC: 0.789) and CA19-9 (sensitivity: 14.99%; specificity: 96.61%; AUC: 0.590). The combination of mSEPT9, CEA, and CA19-9 further improved sensitivity, specificity, and AUC value (sensitivity: 78.43%; specificity: 86.07%; AUC: 0.878), respectively. Notably, the mSEPT9 positivity rate was significantly associated with TNM stage, T stage, N stage, tumor size, vascular invasion, and nerve invasion among patients with CRC. A 100% correlation was observed between the positive results of the mSEPT9 test and recurrence or metastasis in patients after therapeutic intervention. Conclusion: Our findings suggest that mSEPT9 may represent a potential biomarker for the diagnosis and prognosis of CRC compared with CEA and CA19-9. Postoperative mSEPT9 status may represent the first noninvasive marker of CRC recurrence or metastasis.

The Clinicopathological Significance and Prognostic Value of Androgen Receptor in Endometrial Carcinoma: A Meta-Analysis.

Background: The role of androgen receptor (AR) in evaluating the prognosis of patients with endometrial cancer (EC) remains controversial. Here, we performed a meta-analysis to assess whether AR expression improves EC survival outcomes. Methods: We searched related articles published before August 2021 in PubMed, EMBASE, and Web of Science. The association between AR expression and patient prognosis was estimated with hazard ratios (HRs) and odds ratios (ORs) with their corresponding 95% confidence intervals (95% CIs). The review is registered on PROSPERO, registration number: CRD42021268591. Results: Ten studies including 1,485 patients were enrolled in the meta-analysis. The results showed that AR expression in EC tissues was associated with a better survival in crude analyses (HR = 1.63, 95% CI = 1.32-2.02, P < 0.001). However, no significant relation was found after the adjustment of the confounding factors (HR = 1.68, 95% CI = 0.75-3.75, P = 0.205). In subgroup analyses, grade 1-2 disease, stage I-II disease, negative lymph node status, and lack of the lymphovascular invasion were more common in AR-positive groups (OR = 0.47, 0.48, 0.37, and 0.57; 95% CI = 0.45-0.62, 0.35-0.65, 0.24-0.56, and 0.37-0.89). Furthermore, AR expression was more common in endometrioid cancers (OR = 2.39, 95% CI = 1.79-3.20). Conclusions: AR expression is significantly associated favorable characteristics including low-grade disease, early-stage disease, negative lymph node status, and lack of the lymphovascular invasion and a specific histology-endometrioid cancer. However, AR is not an independent prognostic factor.

Who would avoid severe adverse events from nasointestinal tube in small bowel obstruction? A matched case-control study.

BACKGROUND: Nasointestinal tubes (NITs) have been increasingly used in patients with small bowel obstruction (SBO); However, severe adverse events (SAEs) of NITs might threaten the lives of patients. The indications of NITs need to be identified. This study was designed to explore the indications for the insertion of NITs in patients with SBO and to suggest the optimal strategies for individuals based on the outcomes of SAEs. METHODS: After propensity score matching, 68 pairs were included (Success group and failure group). The occurrence of SAEs and the clinical parameters were compared between the SAE group and the non-SAE group. Independent risk factors were evaluated among the subgroups. A novel scoring system was established to detect the subgroups that would benefit from NITs insertion. RESULTS: Successful implementation of NITs could avoid hypochloremia (p = 0.010), SAEs (p = 0.001), pneumonia (p = 0.006). SAEs occurred in 13 of 136 (9.6%) patients who accepted NITs insertion treatment. Risk factors for SAEs included tumors (p = 0.002), reduced BMI (p = 0.048), reduced hemoglobin (p = 0.001), abnormal activated partial thromboplastin time (p = 0.015) and elevated white blood cells (p = 0.002). A novel risk scoring system consists of hemoglobin before NITs insertion (95% CI 0.685, 0.893) and bowel obstruction symptoms relieved after NITs insertion (95% CI 0.575, 0.900) had the highest area under curve for predicting the occurrence of SAEs. We divided the risk score system into 3 grades, with the increasing grades, the rates of SAEs surged from 1.3% (1/74) to (6/11) 54.5%. CONCLUSION: NITs successfully insertion could avoid SAEs occurrence in SBO conservative treatment. SBO patients without anemia and could be relieved after NITs insertion could be the potential benefit group for this therapy.

Discovery of novel rost-4-ene derivatives as potential plant activators for preventing phytopathogenic bacterial infection: Design, synthesis and biological studies.

BACKGROUND: Gradually aggravated disease caused by phytopathogenic bacteria severely restricts food security and crop yield, and few pesticides can relieve this severe situation. Thus, development and excavation of new agrochemicals with high bioactivity and novel action mechanism may be a feasible strategy to control intractable bacterial diseases. As a privileged molecular framework, steroid molecules exhibit diversiform bioactivities. Herein, a series of novel androst-4-ene derivatives were designed, synthesised and investigated for their antibacterial behaviour to excavate novel agrochemicals on the base of steroid molecules. RESULTS: Bioassay results indicated that target compounds displayed high bioactivities toward three destructive phytopathogenic bacteria, including Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas axonopodis pv. citri (Xac) and Pseudomonas syringae pv. actinidiae (Psa). Compound III19 displayed excellent in vitro antibacterial profiling (EC50  = 2.37 mg L-1 towards Xoo, EC50  = 2.10 mg L-1 towards Xac, EC50  = 9.50 mg L-1 towards Psa). Furthermore, compound III19 showed outstanding in vivo protective activities, with values of 81.81% and 58.75% towards kiwifruit bacterial canker and rice bacterial leaf blight, respectively. Analysis of the antibacterial mechanism disclosed that compound III19 enhanced host defence enzyme activities superoxide dismutase (SOD), peroxidase (POD), phenylalanine ammonia lyase (PAL), polyphenol oxidase (PPO), and catalase (CAT) and increased the salicylate synthase content to induce host resistance. In addition, compound III19 increased the membrane permeability, destroyed the cell membrane and killed the bacteria. CONCLUSION: Given these profiles of target compounds, we highlight a new strategy for controlling intractable plant bacterial diseases by inducing plant resistance and targeting the bacterial cell membrane. © 2022 Society of Chemical Industry.

A theoretical library of N1s core binding energies of polynitrogen molecules and ions in the gas phase.

Polynitrogen molecules and ions are important building blocks of high energy density compounds (HEDCs). High energy bonds formed at the N sites can be effectively probed by X-ray photoelectron spectroscopy (XPS) at the N K-edge. In this work, with the density functional theory and the ΔKohn-Sham scheme, we simulated the N1s ionic potentials (IPs) of 72 common polynitrogen molecules [tetrazoles, pentazole (N5H), diazines, triazines, tetrazines, furazans, oxazoles and oxadiazoles], ions [pentazolate anion (cyclo-N5-), pentazenium cation (N5+), etc.], and molecular (NH3⋯N5H, H2O⋯N5H) and ionic (NH4+⋯N5-, H3O+⋯N5-) pairs, as well as mononitrogen relatives. These constitute a small theoretical database for absolute N1s IPs with an average accuracy of ca. 0.3 eV. To understand the structure-IP relationship within this family, effects of side substituent and bridging groups, local bonding types (amine or imine N), charge and protonation states, and vibronic coupling were analyzed based on selected systems. This study in the gas phase collects inherent chemical shifts of nitrogen in high-energy NN and NC bonds, which provides an essential reference into XPS interpretations of more complex HEDCs in the solid state. We especially highlight the evident N1s chemical shifts induced by protonation for nitrogen in the five-membered ring (N5H versus cyclo-N5-, ca. 7 eV; NH3⋯N5H versus NH4+⋯N5-, ca. 3 eV; H2O⋯N5H versus H3O+⋯N5-, ca. 2 eV), and suggest XPS as a sensitive tool in determining the hydrogen positions in pentanitrogen-based HEDCs.

TNFRSF11B Suppresses Memory CD4+ T Cell Infiltration in the Colon Cancer Microenvironment: A Multiomics Integrative Analysis.

Background: Colorectal cancer is a lethal cancer worldwide. Due to the low tumor mutation burden and low proportion of tumor-infiltrating lymphocytes in the microenvironment of most patients, innovative immunotherapeutic approaches need to be identified. Methods: Using the TCGA-COAD dataset (n = 514), we identified TNFRSF11B as a prognostic factor of colon cancer. An immunohistochemistry (IHC) dataset (n = 86), 290 single colorectal cancer cells (GSE81861), and 31 paired colon cancer transcriptional datasets were further applied to validate the function of TNFRSF11B, which was confirmed via fluorescence-activated cell sorting (FACS) analysis. Results: A risk score system consisting of eight immune-related genes (IRGs) (FGFR2, ZC3HAV1L, TNFRSF11B, CD79A, IGHV3-11, IGHV3-21, IGKV2D-30, and IGKV6D-21) was constructed to predict the prognosis of colon cancer patients. Only TNFRSF11B was closely correlated with late-stage lymph node metastasis and worse survival outcomes (p = 0.010, p = 0.014, and p = 0.0061). In our IHC dataset, 72.09% (62/86) of the colon cancer patients had TNFRSF11B overexpression with significantly shorter overall survival times (p = 0.072). High TNFRSF11B expression typically had a later TNM stage (p = 0.067), a higher frequency of lymph node (p = 0.029) and lymphovascular (p = 0.007) invasion, and a higher incidence of pneumonia (p = 0.056) than their counterparts. The expression of six genes (KRT18, ARPC5L, ACTG1, ARPC2, EZR, and YWHAZ) related to pathogenic E. coli infection was simultaneously increased with TNFRSF11B overexpression via gene set enrichment analysis (GSEA). These genes are involved in the regulation of the actin cytoskeleton, shigellosis, bacterial invasion of epithelial cells, and Salmonella infection. Finally, only activated memory CD4+ T cells (p = 0.017) were significantly decreased in the high TNFRSF11B expression group via CIBERSORT comparison, which was confirmed by TIMER2.0 analysis of the TCGA-COAD dataset. We also performed FACS analysis to show that TNFRSF11B decreased the infiltration of central memory CD4+ T cells and effector memory CD4+ T cells in the colorectal cancer microenvironment (all p <0.001). Conclusion: TNFRSF11B acts as a prognostic factor for colon cancer patients and could affect the colon cancer immune response. TNFRSF11B was closely related to lymph node invasion and pathogenic E. coli. infection, which may negatively affect memory-activated CD4+ T cell infiltration in colon cancer.

CDKN2B antisense RNA 1 suppresses tumor growth in human colorectal cancer by targeting MAPK inactivator dual-specificity phosphatase 1.

Aberrant expression of long noncoding RNA cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) has been detected in human colorectal cancer (CRC). This study aimed to investigate the role of CDKN2B-AS1 and the underlying mechanism in human CRC. Gain- and loss-of-function assays were performed to explore the role of CDKN2B-AS1 in the malignant behavior of HCT116 and SW480 CRC cells in vitro and in vivo. RNA pull-down assay was conducted to identify the target of CDKN2B-AS1 in CRC cells. The physical and functional interactions between CDKN2B-AS1 and the target were examined. CDKN2B-AS1 inhibited CRC cell proliferation and migration while promoting apoptosis in vitro via activation of mitogen-activated protein kinase kinases (MEK)/extracellular signal-regulated kinase (ERK)/p38 signaling. CDKN2B-AS1 bound to mitogen-activated protein kinase (MAPK) inactivator dual-specificity phosphatase 1 (DUSP1) in CRC cells. In contrast to CDKN2B-AS1, DUSP1 promoted CRC cell proliferation, suppressed apoptosis and inactivated MEK/ERK/p38 signaling in CRC cells. Furthermore, CDKN2B-AS1 overexpression attenuated DUSP1 expression in normal colonic myofibroblasts and CRC cells. Overexpression of DUSP1 effectively countered the activation of MEK/ERK/p38 signaling induced by CDKN2B-AS1 overexpression or further blocked MEK/ERK/p38 signaling suppressed by CDKN2B-AS1 silencing. In the mouse xenograft model, CDKN2B-AS1 suppressed CRC growth, whereas DUSP1 promoted CRC growth. CDKN2B-AS1 induced cell apoptosis while suppressing EMT (epithelial-mesenchymal transition), whereas DUSP1 suppressed cell apoptosis while inducing EMT in CRC, as evidenced by the alterations in the protein levels of apoptosis and EMT markers in tumor tissue samples. CDKN2B-AS1 regulates CRC cell growth and survival by targeting MAPK inactivator DUSP1.

Free Fatty Acid is a Promising Biomarker in Triage Screening for Patients with Colorectal Cancer: A Case-Control Study.

PURPOSE: The aim of our study was to identify the diagnostic ability of free fatty acids (FFAs) in younger colorectal cancer (CRC) patients by comparing carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). METHODS: Patients screened for CRC at Fujian Medical University Union Hospital from January 2011 to December 2014 were recruited. Patients pathologically diagnosed with CRC or colorectal adenoma (CA) and healthy control participants were included. The enzyme endpoint method was applied to measure FFA levels. Receiver operating characteristic (ROC) curve analysis was performed to further evaluate the diagnostic ability of FFAs. RESULTS: FFA levels in late-stage patients (tumour-node-metastasis (TNM) stages III-IV) were higher than those in early-stage patients (TNM stages I-II) (P=0.02). The FFA levels in CRC patients were higher than those in controls of all ages, those younger than 50 years, males and females (P<0.001), and this difference was larger for patients younger than 50 years and females than for the all ages group. There was no significant difference in the FFA level between CA patients and healthy participants (P=0.53). The area under the curve (AUC) values of FFA, CEA, CA19-9, FFA+CEA, FFA+CA19-9 and FFA+CEA+CA19-9 distinguished CRC patients from controls at all ages, with values of 0.604, 0.731, 0.640, 0.754, 0.678 and 0.758, respectively; however, in the younger CRC patients (age≤50), the AUC values were 0.701, 0.735, 0.669, 0.798, 0.749, and 0.801. The AUC in female patients younger than 50 years was larger than that in males (0.769 vs 0.660), and this value was greater than the value for CEA in males (0.739) and females (0.729). CONCLUSION: The FFA level not only can complement the predictive ability of the CEA and CA19-9 levels but also has a superior predictive ability in female and younger patients with CRC. FFA levels may have a potential role in triage screening of early CRC.

A Hybrid Landslide Displacement Prediction Method Based on CEEMD and DTW-ACO-SVR-Cases Studied in the Three Gorges Reservoir Area.

Accurately predicting the surface displacement of the landslide is important and necessary. However, most of the existing research has ignored the frequency component of inducing factors and how it affects the landslide deformation. Therefore, a hybrid displacement prediction model based on time series theory and various intelligent algorithms was proposed in this paper to study the effect of frequency components. Firstly, the monitoring displacement of landslide from the Three Gorges Reservoir area (TGRA) was decomposed into the trend and periodic components by complete ensemble empirical mode decomposition (CEEMD). The trend component can be predicted by the least square method. Then, time series of inducing factors like rainfall and reservoir level was reconstructed into high frequency components and low frequency components with CEEMD and t-test, respectively. The dominant factors were selected by the method of dynamic time warping (DTW) from the frequency components and other common factors (e.g., current monthly rainfall). Finally, the ant colony optimization-based support vector machine regression (ACO-SVR) is utilized for prediction purposes in the TGRA. The results demonstrate that after considering the frequency components of landslide-induced factors, the accuracy of the displacement prediction model based on ACO-SVR is better than that of other models based on SVR and GA-SVR.

A novel nanozyme based on selenopeptide-modified gold nanoparticles with a tunable glutathione peroxidase activity.

In this study, we successfully prepared a selenium-containing pentapeptide (Sec-Arg-Gly-Asp-Cys)-modified gold nanozyme that exhibited glutathione peroxidase (GPx) activity. The nanozyme catalyzed the reduction of H2O2 by GSH, and its GPx activity was about 14 times that of free selenopeptide. Kinetic analysis indicated that the nanozyme changed the catalytic mechanism from the ping-pong mechanism of the peptide to an ordered mechanism. This indicated that the gold nanoparticle acts as a scaffold that may limit the mobility and constrain the conformation of the peptides, hence exposing the active center to the substrates, and allowing the multivalent selenopeptide to act cooperatively to increase the catalytic rate. Furthermore, upon addition of cysteamine to regulate the surface chemistry of gold nanoparticles and thereby modify the microenvironment of the active center, this nanozyme system could achieve a tunable GPx activity that was about 20 times that of free selenopeptide. Thus, the rational design of the nanozyme greatly improved and amplified the catalytic activity of the 'active unit' peptide. This study provides an alternative strategy to establish GPx mimics and provides new insights for the use of gold nanoparticles to develop nanozymes with biological applications.