Background/Objectives: Ulcerative colitis (UC) has a higher risk of developing colorectal polyps and colorectal cancer (CRC) than non-UC individuals. The aim of the study was to explore the risk factors for coexisted colorectal polyps in patients with UC, especially for coexisted colorectal adenoma. Methods: Patients diagnosed with UC who were admitted to our hospital between January 1, 2015, and December 31, 2022 were enrolled in the study. Patients’ data including demographic data, smoking history, alcohol consumption history, disease related parameters, were retrospectively collected through the Electronic Medical Record System. Results: A total of 549 patients with UC were enrolled, among whom, 261 patients were with colorectal polyps. Within the polyp group, 54 patients had adenomatous polyps. Seven patients were diagnosed with CRC. Multivariate logistic regression revealed age ≤ 40 years, disease duration >10 years, severe disease activity, and non-biologic treatment were risk factors for colorectal polyps in patients with UC; while age > 40 years, disease duration > 10 years, a chronic relapsing disease course, and larger polyps size were risk factors for adenomatous polyps in UC patients; and age > 40 years, disease duration > 10 years, and the presence of polyps were risk factors for CRC in patients with UC. Conclusions: UC patients with a junior age, long disease duration, severe disease activity, and non-biologic treatment are likely to have colorectal polyps. While patients with a senior age, long disease duration, a chronic relapsing disease course, and larger polyp size should be screened for adenomatous polyps, and with senior age, long disease duration, and the presence of polyps should be screened for CRC.

Due to the difficulty in early diagnosis and the lack of treatment for advanced disease, the mortality rate of hepatocellular carcinoma (HCC) is high, and the 5-year overall survival rate is low at present. SLC1A4 is a neutral amino acid transporter, but its regulatory role and mechanism in HCC are still unclear. Through analyzing the TCGA database and clinical tissue specimens, this study uncovered the high expression of SLC1A4 in tumor tissues of HCC. Worse more, a high level of SLC1A4 may lead to a poor prognosis of HCC. Mechanically, silencing SLC1A4 inhibited the phosphorylation activation of AKT by suppressing the ubiquitin modification of AKT at lysine 63 and amino acid influx represented by D-serine, decreasing the protein level of β -catenin in the cell nucleus and suppressing the transcriptional activity of c-Myc and EpCAM promoters. As a result, silencing SLC1A4 inhibited the proliferation, migration, and stemness of hepatic cancer cells, which was successfully reversed by the introduction of exogenous AKT. Moreover, epithelial–mesenchymal transition (EMT) in vitro and metastasis potential in vivo of hepatic cancer cells was suppressed by the downregulated SLC1A4 level. In conclusion, SLC1A4 promotes the malignant transformation of HCC through activating signal transduction mediated by AKT. The findings in this study suggested that SLC1A4 may be a diagnostic indicator for the early HCC and a therapeutic target for the advanced HCC.

Rebleeding is a significant complication of endoscopic injection of cyanoacrylate in gastric varices in cirrhotic patients. This systematic review and meta-analysis aimed to evaluate the efficiency of endoscopic cyanoacrylate injection and summarized the risk factors for rebleeding. Databases were searched for articles published between January 2012 and December 2022. Studies evaluating the efficiency of endoscopic injection of cyanoacrylate glue for gastric varices and the risk factors for rebleeding were included. The final analysis included data from 24 studies. The hemostatic rates ranged from 65 to 100

Tumor relapse and metastasis are the major causes of mortality associated with urothelial cancer. In the tumor microenvironment, negative regulatory molecules and various immune cell subtypes suppress antitumor immunity. The inflammatory microenvironment, associated with neutrophils and neutrophil extracellular traps (NETs), promotes tumor metastasis. However, no drugs are currently available to specifically inhibit neutrophils and NETs. In this study, we first demonstrated that icaritin (ICT), a Chinese herbal remedy that is a first-line treatment for advanced and incurable hepatocellular carcinoma, reduces NETs caused by suicidal NETosis and prevents neutrophil infiltration in the tumor microenvironment. Mechanistically, ICT binds to and inhibits the expression of PADI2 in neutrophils, thereby suppressing PADI2-mediated histone citrullination. Moreover, ICT inhibits ROS generation, suppresses the MAPK signaling pathway, and inhibits NET-induced tumor metastasis. Simultaneously, ICT inhibits tumoral PADI2-mediated histone citrullination, which consequently suppresses the transcription of neutrophil-recruiting genes such as GM-CSF and IL-6. The downregulation of IL-6 expression, in turn, forms a regulatory feedback loop through the JAK2/STAT3/IL-6 axis. Through a retrospective study of clinical samples, we found a correlation between neutrophils, NETs, UCa prognosis, and immune evasion. Combining ICT with immune checkpoint inhibitors may have synergistic effects. In summary, our study demonstrated that ICT could be a novel inhibitor of NETs and a novel UCa treatment.

Supplemental Table 3. Environmental Factors and colorectal cancer: associations by study design

PDF file - 87K, Metformin structure.

(1) Background: Endoscopic submucosal dissection (ESD) has been widely accepted as the standard method for treating early-stage cancer or precancerous lesions in the upper gastrointestinal tract; however, it may be difficult in patients with liver cirrhosis due to clinical challenges such as coagulation dysfunction, presence of gastroesophageal varices, etc. We aimed to demonstrate the safety and efficacy of ESD in these populations. (2) Methods: The clinical data of patients were retrospectively collected and analyzed. Inclusion criteria of the study were: a. patients with liver cirrhosis; b. patients who underwent ESD; c. patients who were diagnosed with early-stage cancer or precancerous lesions in the upper gastrointestinal tract. (3) Results: Eight patients were enrolled from April 2019 to April 2023, of whom three were male and five were female, with ages ranging from 43 to 70 years old. Seven lesions were located in the stomach and one other lesion was in the esophagus. ESD was performed successfully in all eight patients, and the resected lesion size ranged from 2 to 6 cm. Only one patient encountered postoperative complications, namely, chest pain and fever. No recurrence was noticed during a follow-up of 3 to 45 months. (4) Conclusions: ESD may serve as a safe and effective method for treating upper gastrointestinal early-stage cancer or precancerous lesions in patients with liver cirrhosis.

Provides an overview of the methods for each of the included studies

Supplemental Table 1. SNP details, by study

Supplemental Table 2. All GxE interactions

Background Superficial duodenal epithelial lesions are precancerous lesions of duodenal carcinoma. Upper gastrointestinal endoscopy has been widely used in the screening and treatment of this disease. This article will collect the data of patients who underwent endoscopic resection of superficial duodenal epithelial lesions in our hospital from 2010 to 2021, aiming to describe the efficacy and safety of endoscopic resection, as well as to explore the risk factors of non-en bloc resection and non-R0 resection. Methods Patients who underwent endoscopic resection for superficial duodenal epithelial lesions in our hospital from January 2010 to September 2021 were selected. The curative effect was expressed by the en bloc resection rate and R0 resection rate. The safety was expressed by intra- or postoperative complications, such as bleeding and perforation. The potential risk factors of curative effect were analyzed by logistic regression. Results A total of 137 patients were included. The en bloc resection rate was 95.62% (131/137), R0 resection rate was 91.97% (126/137), the postoperative bleeding rate was 2.19% (3/137), and no postoperative perforation was found. The histology result of ectopic gastric mucosa was the risk factor of non-en bloc resection (OR: 8.86, 95% CI: 1.38-56.92); the lesion size ≥2 cm was the risk factor of non-R0 resection (OR: 12.55, 95% CI: 2.95-53.38). Conclusion Endoscopic resection is a safe and effective method for the treatment of superficial duodenal epithelial lesions. The histology result of ectopic gastric mucosa was the risk factor of non-en bloc resection and the lesion size ≥2 cm was the risk factor of non-R0 resection.

In order to improve the adaptability of packaging paper and the high-speed packaging machine, we designed a set of non-contact precision inspection and evaluation system for the packaging paper products. A macro laser scanning sensor is installed on bi-axial linear motor for sampling the full dimension of paper on the negative pressure adsorption platform, the uniform sampling density is designed higher than 1100 spots/ mm2, and theoretical error of depth data is less than 0.02mm, this method solved two defects in contacting measurement: the data can't cover object's surface completely, and it is hard to avoid deformation of the measured object. Based on full covered data, this paper proposed the algorithms of Image visualization, indentation detection, contour fitting, 3D reconstruction, and a norm of parameters based on local frequency changes was designed by consulting with industrial demand. The experiment shows that this method can significantly reflect the micro differences. The system could export measurement report and provides an interactive measurement in 3D visualization window, so this work is helpful at development of process control in printing industry, such as defectiveness detection, adaptability verification.

Liver fibrosis is an inevitable stage in the development of chronic liver disease to cirrhosis. Nonetheless, the interventional treatment and achieving control over the disease at this stage can substantially reduce the incidence of liver cirrhosis. To demonstrate these aspects, liver pathological sections of 18 patients with chronic liver disease are collected for research according to the degree of fibrosis. Further, the expressions of related proteins in each group are studied by the Western blot method. The cell proliferation and apoptosis are detected by CKK-8 and flow cytometry analyses. Further, a rat model with carbon tetrachloride (CCl4)-induced liver fibrosis is employed to verify the effect and mechanism of VDR on the process of liver fibrosis in vivo. The expression of VDR in liver tissues of patients with liver fibrosis is negatively correlated with α-smooth muscle actin (α-SMA), Col-1, and liver fibrosis stages. Moreover, the tumor necrosis factor (TNF)-α stimulation could increase the proliferation of LX-2, up-regulate the expression of α-SMA, Col-1, NF-κB, p-IκBα, p-IKKβ, p-p65m, and some fibrosis factors, as well as down-regulate the expressions of VDR and matrix metalloproteinase-1 (MMP-1). Considering the protective actions of VDR, calcipotriol, a VDR agonist, effectively reduced the degree of liver fibrosis in a rat model of liver fibrosis by inhibiting the deposition of extracellular (ECM) and activation of hepatic stellate cells (HSCs), which is negatively correlated with the degree of liver fibrosis. Together, these shreds of evidence demonstrated that the calcipotriol showed great potential in effectively attenuating liver fibrosis.

Background Pancreatic ductal adenocarcinoma (PDAC) is one of the most commonly diagnosed cancers with a poor prognosis worldwide. Although the treatment of PDAC has made great progress in recent years, the therapeutic effects are still unsatisfactory. Methods. In this study, we identified differentially expressed genes (DEGs) between PDAC and normal pancreatic tissues based on four Gene Expression Omnibus (GEO) datasets (GSE15471, GSE16515, GSE28735 and GSE71729). A protein–protein interaction (PPI) network was established to evaluate the relationship between the DEGs and to screen hub genes. The expression levels of the hub genes were further validated through the Gene Expression Profiling Interactive Analysis (GEPIA), ONCOMINE and Human Protein Atlas (HPA) databases, as well as the validation GEO dataset GSE62452. Additionally, the prognostic values of the hub genes were evaluated by Kaplan–Meier plotter and the validation GEO dataset GSE62452. Finally, the mechanistic roles of the most remarkable hub genes in PDAC were examined through in vitro experiments. Results We identified the following nine hub genes by performing an integrated bioinformatics analysis: COL1A1, COL1A2, FN1, ITGA2, KRT19, LCN2, MMP9, MUC1 and VCAN. All of the hub genes were significantly upregulated in PDAC tissues compared with normal pancreatic tissues. Two hub genes (FN1 and ITGA2) were associated with poor overall survival (OS) rates in PDAC patients. Finally, in vitro experiments indicated that FN1 plays vital roles in PDAC cell proliferation, colony formation, apoptosis and the cell cycle. Conclusions In summary, we identified two hub genes that are associated with the expression and prognosis of PDAC. The oncogenic role of FN1 in PDAC was first illustrated by performing an integrated bioinformatic analysis and in vitro experiments. Our results provide a fundamental contribution for further research aimed finding novel therapeutic targets for overcoming PDAC.

Introduction The clinical performance of [–2]proPSA (p2PSA) and its derivatives in predicting the presence and aggressiveness of prostate cancer (PCa) has been well evaluated in prostate biopsy patients. However, no study has been performed to evaluate the common genetic determinants that affect serum level of p2PSA. Materials and Methods Here, we performed a two-stage genome-wide association study (GWAS) on the p2PSA level in Chinese men who underwent a transperineal ultrasound-guided prostate biopsy at Huashan Hospital, Shanghai Cancer Center, and Ruijin Hospital in Shanghai, China. Germline variants significantly associated with the p2PSA level in the first stage (n = 886) were replicated in the second stage (n = 1,128). Multivariate linear regression was used to assess the independent contribution of confirmed single nucleotide polymorphisms (SNPs) and known covariates, such as age, to the level of p2PSA. Results A novel non-synonymous SNP, rs72725879, in region 8q24.21 of the PRNCR1 gene was significantly associated with the serum level of p2PSA in this two-stage GWAS (p = 2.28 × 10−9). Participants with homozygous “T” alleles at rs72725879 had higher p2PSA levels compared to allele “C” carriers. This variant was also nominally associated with PCa risk (p-combined = 3.44 × 10−18). The association with serum level of p2PSA was still significant after adjusting for PCa risk and age (p = 0.017). Conclusions Our study shows that the genetic variants in the 8q24.21 region are associated with the serum level of p2PSA in a large-scale Chinese population. By taking inherited variations between individuals into account, the findings of these genetic variants may help improve the performance of p2PSA in predicting prostate cancer.

Bladder cancer is a severe cancer with high mortality because of invasion and metastasis. Growing evidence has revealed that circular RNAs play critical roles in biological function, which is closely connected to proliferation and invasion of bladder cancer. In our study, we employed qRT-PCR, RNA fluorescence in situ hybridization (FISH), 5-ethynyl-2'-deoxyuridine (EdU), CCK-8, Transwell assays, luciferase reporter assays, xenografts, and live imaging to detect the roles of circular RNA binding protein with multiple splicing (circRBPMS) in bladder cancer (BC). Bioinformatics analysis and WB were performed to investigate the regulatory mechanism. Expression profile analysis of circular RNAs (circRNAs) in BC revealed that circRBPMS was significantly downregulated. Low circRBPMS expression correlates with aggressive BC phenotypes, whereas upregulation of circRBPMS suppresses BC cell proliferation and metastasis by directly targeting the miR-330-3p/ retinoic acid induced 2 (RAI2) axis. miR-330-3p upregulation or silencing of RAI2 restored BC cell proliferation, invasion, and migration following overexpression of circRBPMS. RAI2 silencing reversed miR-330-3p-induced cell invasion and migration as well as growth inhibition in vitro. Moreover, through bioinformatic analysis of the downstream target of RAI2 in the TCGA database, we identified and validated the biological role of circRBPMS through the RAI2-mediated ERK and epithelial-mesenchymal transition (EMT) pathways. We summarize the circRBPMS/miR-330-3p/RAI2 axis, where circRBPMS acts as a tumor suppressor, and provide a potential biomarker and therapeutic target for BC.

There is little information on the role of microRNA (miR)-922 in the malignant behavior of liver cancer. The present study investigated the regulation of miR-922 expression levels by cAMP response element binding protein 1 (CREB1) in liver cancer tissue, its role in regulating malignant behavior and its potential targets in liver cancer. miR-922 expression in liver cancer cells and tissue was determined by reverse transcription-quantitative PCR. The binding of CREB1 to the promoter region of mir-922 was tested by chromatin immunoprecipitation-PCR. The predicted AT-rich interactive domain 2 (ARID2) and fidgetin, microtubule severing factor targets of miR-922 were characterized by dual luciferase reporter assay. The effects of altered ARID2 expression levels on miR-922-enhanced malignant behavior of liver cancer cells were tested. CREB1 bound to the promoter region of miR-922. Elevated miR-922 transcripts were inversely associated with ARID2 expression in liver cancer tissue and cells. miR-922 inhibited ARID2-regulated luciferase expression and was present in the miR/argonaute RISC catalytic component 2 complex. ARID2 significantly decreased malignant behavior of liver cancer MHCC97L cells. Similarly, ARID2 over-expression inhibited growth of xenograft liver cancer tumors and decreased miR-922, Bcl-2, proliferating cell nuclear antigen, cyclin D1, MMP3 and MMP9 expression and serum VEGF and TNF-alpha levels, but enhanced Bax expression levels in tumors. ARID2 over-expression abrogated malignant behavior promoted by miR-922 over-expression and enhanced miR-922-decreased malignant behavior of liver cancer cells. CREB induced miR-922 transcription, which targeted ARID2 to enhance malignant behavior of liver cancer cells, indicating that the CREB1/miR-922/ARID2 axis may be a potential target for liver cancer treatment.