ARHGAP4 promotes colon cancer metastasis through the TGF-ß signaling pathway and may be associated with T cell exhaustion.

BACKGROUND: Colon cancer is a prevalent invasive neoplasm in the gastrointestinal system with a high degree of malignancy. Despite extensive research, the underlying mechanisms of its recurrence and metastasis remain elusive.Rho GTPase activating protein 4 (ARHGAP4), a member of the small GTPases protein family, may be closely related to tumor metastasis, and its expression is increased in colon cancer. However, the role of ARHGAP4 in colon cancer metastasis is uncertain. This study investigates the impact of ARHGAP4 on the metastasis of colon cancer cells. Our objective is to determine the role of ARHGAP4 in regulating the invasive behavior of colon cancer cells. METHODS: We downloaded colon adenocarcinoma (COAD) data from the Cancer Genome Atlas (TCGA), and performed differential analysis and survival analysis. By using the CIBERSORT algorithm, we evaluated the proportion of infiltrating immune cells in colon cancer. We further analyzed whether ARHGAP4 is associated with T cell exhaustion. Finally, we investigated the impact of ARHGAP4 knockdown on the migration and invasion of colon cancer cells through in vitro cell experiments. Additionally, we utilized western blotting to assess the expression of protein related to the TGF-ß signaling pathway and epithelial-mesenchymal transition (EMT). RESULTS: We found that ARHGAP4 is upregulated in colon cancer. Subsequent survival analysis revealed that the high-expression group had significantly lower survival rates compared to the low-expression group. Immune infiltration analysis showed that ARHGAP4 was not only positively correlated with CD8+ T cells, but also positively correlated with T cell exhaustion markers programmed cell death 1 (PDCD-1), cytotoxic T-lymphocyte associated protein 4 (CTLA-4), and lymphocyte activating 3 (LAG-3). In vitro cell experiments, the knockdown of ARHGAP4 inhibited the migration and invasion of colon cancer cells. Among EMT-related proteins, when ARHGAP4 was knocked down, the expression of E-cadherin was increased, while the expression of N-cadherin and Vimentin was decreased. Meanwhile, the expression of TGF-ß1, p-Smad2, and p-Smad3, which are associated with the TGF-ß/Smad pathway, all decreased. CONCLUSION: ARHGAP4 promotes colon cancer metastasis through the TGF-ß/Smad signaling pathway and may be associated with T cell exhaustion. It plays an important role in the progression of colon cancer and may serve as a potential target for diagnosis and treatment of colon cancer.

OLFM2 promotes epithelial-mesenchymal transition, migration, and invasion in colorectal cancer through the TGF-ß/Smad signaling pathway.

BACKGROUND: Colorectal cancer (CRC) is an aggressive tumor of the gastrointestinal tract, which is a major public health concern worldwide. Despite numerous studies, the precise mechanism of metastasis behind its progression remains elusive. As a member of the containing olfactomedin domains protein family, olfactomedin 2 (OLFM2) may play a role in tumor metastasis. It is highly expressed in colorectal cancer, and its role in the metastasis of CRC is still unclear. As such, this study seeks to explore the function of OLFM2 on CRC metastasis and its potential mechanisms. METHODS: Real-time fluorescence quantitative PCR and western blotting were used to study the expression of OLFM2 in human CRC and adjacent normal tissues. Knockdown and overexpression OLFM2 cell lines were constructed using siRNA and overexpression plasmids to explore the role of OLFM2 in the migration and invasion of CRC through transwell, and wound healing experiments. Finally, the expression of epithelial-mesenchymal transition (EMT) -related proteins and TGF-ß/Smad signaling pathway-related proteins was investigated using western blotting. RESULTS: In this study, we observed an elevation of OLFM2 expression levels in CRC tissues. To investigate the function of OLFM2, we overexpressed and knocked down OLFM2. We discovered that OLFM2 knockdown inhibited migration and invasion of colon cancer cells. Furthermore, E-cadherin expression increased while N-cadherin and Vimentin expression were opposite. It is no surprise that overexpressing OLFM2 had the opposite effects. We also identified that OLFM2 knockdown resulted in reduced TGF-ßR1 and downstream molecules p-Smad2 and p-Smad3, which are related to the TGF-ß / Smad pathway. In contrast, overexpressing OLFM2 significantly boosted their expression levels. CONCLUSION: The protein OLFM2 has been identified as a crucial determinant in the progression of CRC. Its mechanism of action involves the facilitation of EMT through the TGF-ß/Smad signaling pathway. Given its pivotal role in CRC, OLFM2 has emerged as a promising diagnostic and therapeutic target for the disease. These results indicate the potential of OLFM2 as a valuable biomarker for CRC diagnosis and treatment and highlight the need for further research exploring its clinical significance.

Reduced Adenoma Miss Rate With 9-Minute vs 6-Minute Withdrawal Times for Screening Colonoscopy: A Multicenter Randomized Tandem Trial.

INTRODUCTION: Although the 9-minute mean withdrawal time (m-WT) is often reported to be associated with the optimal adenoma detection rate (ADR), no randomized trials of screening colonoscopy have confirmed the impact of a 9-minute m-WT on adenoma miss rate (AMR) and ADR. METHODS: A multicenter tandem trial was conducted in 11 centers. Seven hundred thirty-three asymptomatic participants were randomized to receive segmental tandem screening colonoscopy with a 9-minute withdrawal, followed by a 6-minute withdrawal (9-minute-first group, 9MF, n = 366) or vice versa (6-minute-first group, 6MF, n = 367). The primary outcome was the lesion-level AMR. RESULTS: The intention-to-treat analysis revealed that 9MF significantly reduced the lesion-level (14.5% vs 36.6%, P < 0.001) and participant-level AMR (10.9% vs 25.9%, P < 0.001), advanced adenoma miss rate (AAMR, 5.3% vs 46.9%, P = 0.002), multiple adenomas miss rate (20.7% vs 56.5%, P = 0.01), and high-risk adenomas miss rate (14.6% vs 39.5%, P = 0.01) of 6MF without compromising detection efficiency ( P = 0.79). In addition, a lower false-negative rate for adenomas ( P = 0.002) and high-risk adenomas ( P < 0.05), and a lower rate of shortening surveillance schedule ( P < 0.001) were also found in 9MF, accompanying with an improved ADR in the 9-minute vs 6-minute m-WT (42.3% vs 33.5%, P = 0.02). The independent inverse association between m-WT and AMR remained significant even after adjusting ADR, and meanwhile, 9-minute m-WT was identified as an independent protector for AMR and AAMR. DISCUSSION: In addition to increasing ADR, 9-minute m-WT also significantly reduces the AMR and AAMR of screening colonoscopy without compromising detection efficiency.

Twenty-year span of global acute pancreatitis trends: A bibliometric analysis.

OBJECTIVE: This study aims to investigate the global research routine and trends of acute pancreatitis over the last twenty years based on the production, hotspots, and frontiers of published articles as well as to provide the global health system with a bibliometric reference. METHODS: The Web of Science core collection database was retrieved for acute pancreatitis original articles and review articles published from January 1, 1999 to May 17, 2020. Duplicates and discrete papers were excluded. Articles were evaluated for several characteristics including number of citations, publication time, country of origin, institution, journal and authorship. RESULTS: A total of 7001 articles originated from 94 countries and were published in 1263 journals. The China contributed most articles (1752) followed by USA (1214). The research was major published in specialized journals including the Pancreas (511) and pancreatology (351). Universities were the main institutions of science progress. High-impact articles focused on the fields of clinical medicine. A steady growth was observed in the last 20 years from 1999 to 2020. CONCLUSION: This comprehensive bibliometric study indicates that severe acute pancreatitis and necrotizing pancreatitis are significant topic in the acute pancreatitis research. The structured information may be helpful in understanding research trends, and locating research hot spots and gaps in this domain.

Establishment and evaluation of a nomogram predicting risks of missed diagnoses of colorectal polyps.

BACKGROUND: A missed diagnosis of colorectal polyps during colonoscopy may be associated with the occurrence of interval colorectal cancer. The risk factors for a missed diagnosis or a method to predict the risk of a missed diagnosis of colorectal polyps during colonoscopy remain unidentified. METHODS: The clinical data of patients who underwent two colonoscopies within three months at the Affiliated Hospital of North Sichuan Medical College between February 2017 and August 2019 were retrospectively reviewed. Independent risk factors for missed diagnoses were identified, and a nomogram was established to predict the risk of missed diagnoses. The prediction performance of the nomogram was evaluated using C-index and calibration curves, and its clinical application value was assessed using the Youden index and decision curve analysis. RESULTS: Independent influencing factors for missed diagnoses included age, endoscopist experience, bowel preparation, retroflected view, withdrawal time, number of polyps in the right colon, and number of polyps ≥ 6 mm. The C-index of the nomogram in the training and validation cohorts was 0.763 (95% confidence interval [CI]: 0.724 - 0.807) and 0.726 (95%CI: 0.657 - 0.794), respectively. The optimal cut-off value of the nomogram calculated using the Youden index was 152.2 points. Under the cut-off value, the sensitivity, specificity, positive predictive value, and negative predictive value were 67.1%, 75.7%, 45.8%, and 88.2%, respectively, in the training cohort, and 57.1%, 79.9%, 53.3%, and 82.3%, respectively, in the validation cohort. CONCLUSIONS: The nomogram provides a reference value for clinicians to analyse the risk of a missed diagnosis of colorectal polyps in individuals, identify high-risk groups, and formulate appropriate follow-up strategies.

NLRP3 inflammasome inhibitor CY-09 reduces hepatic steatosis in experimental NAFLD mice.

AIMS: Non-alcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases. The NOD-like receptor protein 3 (NLRP3) inflammasome was suggested to be involved in the pathogenesis of NAFLD. A small-molecule named CY-09 is a new selective and direct inhibitor of the NLRP3 inflammasome. We aimed to investigate whether CY-09 is effective for the treatment of NAFLD in a high-fat diet (HFD)-induced mouse model. METHODS: Twenty mice were fed by HFD for 14 weeks, and then were randomly assigned into two groups: (1) control group receiving dimethylsulfoxide (DMSO) solution; (2) CY-09 group receiving CY-09 injection. In an 8-week follow-up, oral glucose tolerance test (OGTT) and homeostasis model assessment of insulin resistance (HOMA-IR) were used to measure glucose metabolism. Liver steatosis was evaluated by the NAFLD activity score (NAS) and deemed as the primary outcome. RESULTS: The body weight in CY-09 group was significantly lower than the DMSO control group on 27 weeks (41.0 ± 3.5 g vs. 49.7 ± 5.2 g, P = 0.014). The area under the curve (AUC) of OGTT was less in CY-09 group than that in DMSO group (35.81 ± 6.79 vs. 22.91 ± 2.58 mmol/L·hr, P = 0.004), as well as HOMA-IR (14.36 ± 3.89 vs. 8.82 ± 2.04 mmol.mIU.L-2, P = 0.023). Microscopically, liver lipid droplets dramatically improved and significantly lower NAS was observed in CY-09 group (8.25 ± 1.26 vs. 3.20 ± 0.45, P < 0.001). CONCLUSION: CY-09 reduces hepatic steatosis in experimental NAFLD mice and CY-09 may be a potential therapeutic drug of NAFLD in clinical practice.

Long-term outcomes of endoscopic treatment for colorectal laterally spreading tumor: a large-scale multicenter retrospective study from China.

BACKGROUND: Laterally spreading tumor (LST) is a type of precancerous lesion of colorectal cancer with high malignant potential. The present study aimed to evaluate long-term outcomes of endoscopic treatment for LST in Chinese patients. METHODS: This study was a retrospective review of data collected from 653 included patients with LST from six regional representative hospitals in China between January 2007 and January 2017. Demographic characteristics, endoscopic features of LST, operation-related data, and follow-up results were collected and analyzed. RESULTS: LST-granular type (LST-G, 80.3%) was much more common than LST-non-grandular type (LST-NG, 19.7%). The overall submucosal invasion rate of all LSTs was 6.1% and the submucosal invasion rate of LST-NG was significantly higher than that of LST-G (6.79% vs. 3.87%, p = 0.000). The en bloc resection rate of ESD and EMR treatment was 96% and 93.7%, respectively, with pathologic R0 resection rate of 90.1% and 82.8%. After an average duration of follow-up about 34.52 ± 11.76 months, the recurrence rate of ESD was 3.47%, and the recurrence rate of EMR was 8.8% after an average follow-up of about 38.44 ± 4.42 months. However, the recurrence rate of ESD was much lower than piecemeal EMR for LST (3.47% vs. 8.62%, p = 0.017). Retroflexion-assisted technique applied for resection of rectal LST was associated with a significantly shortened operating time (85.40 min vs. 174.18 min, p = 0.002). CONCLUSION: Endoscopic resection is a safe and efficient modality for the treatment of colorectal LST with a relatively low recurrence rate and shortened operating time with the use of retroflexion.

Alterations in the gut microbiota of patients with acquired immune deficiency syndrome.

Acquired immune deficiency syndrome (AIDS), caused by infection with human immunodeficiency virus (HIV), is associated with gastrointestinal disease, systemic immune activation and changes in the gut microbiota. Here, we aim to investigate the gut microbiota patterns of HIV-infected individuals and HIV-uninfected individuals in populations from South China. We enrolled 33 patients with HIV (14 participants treated with highly active antiretroviral therapy [HAART] for more than 3 months; the remaining 19 individuals had not received treatment) and 35 healthy controls (HC) for a cross-sectional comparison of gut microbiota using stool samples. Gut microbial communities were profiled by sequencing the bacterial 16S rRNA genes. Dysbiosis was more common among patients with AIDS compared with healthy individuals. Dysbiosis was characterized by decreased α-diversity, low mean counts of Bacteroidetes, Faecalibacterium, Prevotella, Bacteroides vulgatus, Dialister and Roseburia inulnivorans, and high mean counts of Proteobacteria, Enterococcus, Streptococcus, Lactobacillus, Lachnociostridium, Ruminococcus gnavus and Streptococcus vestibularis. Increased abundance of Bacilli was observed in homosexual patients. Proteobacteria were higher among heterosexual patients with HIV infections. Tenericutes were higher among patients with history of intravenous drug abuse. Restoration of gut microbiota diversity and a significant increase in abundance of Faecalibacterium, Blautia and Bacteroides were found in patients receiving HAART compared to those who did not receive. HIV infection-associated dysbiosis is characterized by decreased levels of α-diversity and Bacteroidetes, increased levels of Proteobacteria and the alterations of gut microbiota correlate with the route of HIV transmission. The imbalanced faecal microbiota of HIV infection is partially restored after therapy.

Risk factors associated with the detection and missed diagnosis of colorectal flat adenoma: a Chinese multicenter observational study.

OBJECTIVES: Flat colorectal adenomas have a high risk of malignancy; however, their detection is often difficult due to their flat morphology. In this retrospective, large-scale study, we investigated the prevalence and characteristics of flat adenomas in a population in China. METHODS: We analyzed the data collected for 16951 consecutive patients who underwent colonoscopy at four participating hospitals between September 2013 and September 2015. All colonoscopies were performed without magnification. RESULTS: Among the 1,6951 patients, 2938 (17.3%) had adenoma and 796 (4.7%) had flat adenomas. The detection of flat adenoma showed a weak correlation with the detection of adenoma (r = 0.666). Multivariable logistic regression analysis revealed the following independent factors influencing the detection of flat adenomas: patient-related factors of age, presence of warning symptoms, history of adenomas and bowel preparation as well as endoscopist-related factors of endoscopist's level of proficiency, number of colonoscopy operators and withdrawal time. CONCLUSIONS: The prevalence of flat adenomas in our study on Chinese patients was consistent with that reported from other countries. Factors conducive to the detection of flat adenomas were patient age of > 60 years, warning symptoms, history of adenoma, good bowel preparation, experienced endoscopist, single-operator colonoscopy and colonoscopy withdrawal time of >6 min.

Retroflexion-assisted endoscopic mucosal resection: a useful and safe method for removal of low rectal laterally spreading tumors.

BACKGROUND AND AIM: Lesions below or involving the dentate line cannot be removed by standard forward-viewing endoscopic mucosal resection (EMR). Data about retroflexion technique applied during EMR for low rectal laterally spreading tumors (LSTs) are quite limited. Therefore, we aimed to determine the efficacy and safety of retroflexion-assisted EMR (REMR) for the removal of large LSTs from the lower rectum. PATIENTS AND METHODS: EMR employing a complete retroflexion technique was performed in 49 consecutive patients (28 men, 21 women; mean age 51.8 years) with low rectal LSTs that were considered unresectable by conventional forward-viewing EMR due to the narrow and poor endoscopic view. Colonoscopy follow-up data were collected after resection. RESULTS: The low rectal LSTs had a median size of 51 mm (range 30-85 mm). All the tumors were successfully resected in two sessions (median procedure time 57.4 min, range 29-126 min). Procedure-related early bleeding occurred in 14 patients, and delayed hemorrhage occurred in four patients. Serious complications such as perforation or anal dysfunction were not observed, and any procedure-related bleeding was well controlled. The median follow-up period was 8.4 months (range 3-36 months). Nine patients (nine out of 49, 18.4%) experienced recurrence based on follow-up colonoscopy examinations, and the recurrent lesion was completely eradicated by additional endoscopic treatments. CONCLUSIONS: This is the first pilot study to evaluate the efficacy and safety of REMR for removal of low rectal LSTs. The short-term outcomes observed in this study indicate that REMR is a valuable method for the removal of low rectal LSTs. However, further studies evaluating the long-term efficacy and comparing REMR with other interventional therapies are needed.

Endoscopic submucosal dissection for the treatment of rectal carcinoid tumors 7-16 mm in diameter.

OBJECTIVE: Small rectal carcinoid tumors (<10 mm) are often removed via endoscopic submucosal dissection (ESD). However, the use of ESD for tumors of an intermediate size (7-16 mm) is less well documented. This study aimed to evaluate the efficacy and safety of ESD compared with endoscopic mucosal resection using a cap (EMR-C) for the treatment of 7-16-mm rectal carcinoids. MATERIAL AND METHODS: From September 2007 to August 2012, 55 patients with large rectal carcinoid tumors were treated by EMR-C (30 cases) or ESD (25 cases). The en bloc resection rate, pathological complete response (pCR) rate, procedure time, and incidence rates of complications, local recurrence, and distant metastasis were evaluated. RESULTS: The basic and clinical characteristics of the patients in the two groups did not differ significantly (p > 0.05). The mean procedure time was longer for ESD than EMR-C (24.79 ± 4.89 vs. 9.52 ± 2.14 min, p < 0.001). The rates of en bloc resection and pCR were higher with ESD than with EMR-C (100 vs. 83.33 %, and 100 vs. 70.00 %, respectively). No patients in the EMR-C group experienced complications. However, in the ESD group, two cases of perforation occurred, and one patient experienced delayed bleeding. These complications were successfully managed via endoscopical therapy. Five cases of local recurrence were detected after EMR-C, whereas no patients experienced recurrence after ESD. CONCLUSIONS: Compared with EMR-C, ESD appears to be a more favorable therapeutic option for the treatment of rectal carcinoid tumors less than 16 mm in diameter based on improved rates of pCR and local recurrence.

Downregulation of RCN1 inhibits esophageal squamous cell carcinoma progression and M2 macrophage polarization.

Reticulocalbin 1 (RCN1) is a calcium-binding protein involved in the regulation of calcium homeostasis in the endoplasmic reticulum. The aim of this study was to explore the clinical value and biological role of RCN1 in esophageal squamous cell carcinoma (ESCC). In addition, we investigated the effect of RCN1 on the polarization of tumor-associated macrophages (TAMs). The GSE53625 dataset from the Gene Expression Omnibus database was used to analyze the expression of RCN1 mRNA and its relationship with clinical value and immune cell infiltration. Immunohistochemistry was used to validate the expression of RCN1 and its correlation with clinicopathological characteristics. Subsequently, transwell and cell scratch assays were conducted to evaluate the migration and invasion abilities of ESCC cells. The expression levels of epithelial-mesenchymal transition (EMT)-related proteins were evaluated by western blot, while apoptosis was detected by flow cytometry and western blot. Additionally, qRT‒PCR was utilized to evaluate the role of RCN1 in macrophage polarization. RCN1 was significantly upregulated in ESCC tissues and was closely associated with lymphatic metastasis and a poor prognosis, and was an independent prognostic factor for ESCC in patients. Knockdown of RCN1 significantly inhibited the migration, invasion, and EMT of ESCC cells, and promoted cell apoptosis. In addition, RCN1 downregulation inhibited M2 polarization. RCN1 is upregulated in ESCC patients and is negatively correlated with patient prognosis. Knocking down RCN1 inhibits ESCC progression and M2 polarization. RCN1 can serve as a potential diagnostic and prognostic indicator for ESCC, and targeting RCN1 is a very promising therapeutic strategy.

Combination therapy of infliximab and thalidomide for refractory entero-Behcet's disease: a case report.

BACKGROUND: Behcet's disease (BD) is a systemic inflammatory disease with the histopathological features of leukocytoclastic vasculitis that affects nearly all organs and systems. When it involves the intestine, it is called entero-Behcet's disease (entero-BD). CASE PRESENTATION: Here we described a 23-year-old man with entero-BD refractory to conventional therapies who responded well to the combination therapy of infliximab, an anti-tumor-necrosis-factor (TNF)-alpha antibody, and thalidomide. After combination treatment, the patient's symptoms improved greatly and his Crohn's Disease Activity Index (CDAI) score decreased from 344 to 52 points, accompanied by a body weight increase from 53 kg to 64 kg. A follow-up endoscopy performed 10 weeks after the treatment showed significant improvement and the patient's multiple ulcers had healed well. CONCLUSION: The combination therapy of infliximab and thalidomide appears to be clinically effective in a patient with refractory entero-BD. However, further studies need to be performed to evaluate the efficacy of this combination therapy.

UiO-66 derived ZrO2@C catalysts for the double-bond isomerization reaction of 2-butene.

1-Butene, as one of the widely used chemical raw materials, can be produced by the double bond isomerization of 2-butene. However, the current yield of the isomerization reaction is only up to 20% or so. It is therefore an urgent issue to develop novel catalysts with higher performances. In this work, a high-activity ZrO2@C catalyst that is derived from UiO-66(Zr) is fabricated. The catalyst is prepared by calcining the precursor UiO-66(Zr) at high temperature in nitrogen, and characterized by XRD, TG, BET, SEM/TEM, XPS and NH3-TPD. The results demonstrate that the calcination temperature has significant influences on the catalyst structure and performance. Regarding the catalyst ZrO2@C-500, the selectivity and yield of 1-butene are 94.0% and 35.1%, respectively. The high performance is due to multiple aspects, including the inherited octahedral morphology from parent UiO-66(Zr), suitable medium-strong acidic active sites and high surface area. The present work will lead to a better understanding of the ZrO2@C catalyst and guide the rational design of high-activity catalysts for the double bond isomerization of 2-butene to 1-butene.

Development and validation of a prognostic model for mitophagy-related genes in colon adenocarcinoma: A study based on TCGA and GEO databases.

BACKGROUND: Mitophagy is used by eukaryotic cells to eliminate damaged mitochondria. The deregulation of this process can lead to an accumulation of dysfunctional mitochondria and is implicated in carcinogenesis and tumorigenesis. Despite increasing evidence that mitophagy is involved in the development of colon cancer, the role of mitophagy-related genes (MRGs) in colon adenocarcinoma (COAD) prognosis and treatment remains largely unknown. METHODS: Differential analysis was used to identify differentially expressed mitophagy-related genes associated with COAD and conduct key module screening. Cox regression and least absolute shrinkage selection operator, and other analyses were used to characterize prognosis-related genes and verify the feasibility of the model. The model was tested using GEO data and a nomogram was constructed for future clinical application. The level of immune cell infiltration and immunotherapy were compared between the two groups, and sensitivity to treatment with many commonly used chemotherapeutic agents was assessed in individuals with different risk factors. Finally, qualitative reverse transcription polymerase chain reaction and western blotting were performed to assess the expression of prognosis-related MRGs. RESULTS: A total of 461 differentially expressed genes were mined in COAD. Four prognostic genes, PPARGC1A, SLC6A1, EPHB2, and PPP1R17, were identified to construct a mitophagy-related gene signature. The feasibility of prognostic models was assessed using Kaplan-Meier analysis, time-dependent receiver operating characteristics, risk scores, Cox regression analysis, and principal component analysis. At 1, 3, and 5 years, the area under the receiver operating characteristic curves were 0.628, 0.678, and 0.755, respectively, for TCGA cohort, and 0.609, 0.634, and 0.640, respectively, for the GEO cohort. Drug sensitivity analysis found that camptothecin, paclitaxel, bleomycin, and doxorubicin were significantly different between low- and high-risk patients. The qPCR and western blotting results of clinical samples further confirmed the public database results. CONCLUSIONS: This study successfully constructed a mitophagy-related gene signature with significant predictive value for COAD, informing new possibilities for the treatment of this disease.

Morphometric features of gastric mucosa in atrophic gastritis: A different pattern between corpus and antrum.

Atrophic gastritis can cause mucosa thinning, while detailed metrological evidence is lacking. We aimed to compare the morphological features of full-thickness gastric mucosa in antrum and corpus and evaluate the diagnostic performance for atrophy. Gastric cancer patients were prospectively enrolled (N = 401). Full-thickness gastric mucosa was obtained. Foveolar length, glandular length and musculus mucosae thickness were measured. Pathological assessment was conducted using the visual analogue scale of the updated Sydney system. Areas under the receiver operating characteristic curves (AUCs) were calculated for different atrophy degrees. In corpus mucosa, foveolar length and musculus mucosae thickness were positively correlated with the atrophy degree (spearman's correlation coefficient [rs] = 0.231 and 0.224, respectively, P < .05); glandular length and total mucosal thickness were negatively correlated (rs = -0.399 and -0.114, respectively, P < .05). Total mucosal thickness did not correlate with antral atrophy degree (P = .107). The AUCs of total mucosal thickness for corpus and antral atrophy were 0.570 (P < .05) and 0.592 (P < .05), respectively. The AUCs for corpus atrophy, moderate and severe, and severe atrophy were 0.570 (P < .05), 0.571 (P = .003), and 0.584 (P = .006), respectively. The corresponding AUCs for antral atrophy were 0.592 (P = .010), 0.548 (P = .140), and 0.521 (P = .533), respectively. The tendency for mucosal thickness to thin with atrophy occurred in the corpus rather than in the antrum. The diagnostic performance of corpus and antral mucosal thickness was limited for atrophy.

A novel prognostic model based on urea cycle-related gene signature for colorectal cancer.

Background: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the world. This study aimed to develop a urea cycle (UC)-related gene signature that provides a theoretical foundation for the prognosis and treatment of patients with CRC. Methods: Differentially expressed UC-related genes in CRC were confirmed using differential analysis and Venn diagrams. Univariate Cox and least absolute shrinkage and selection operator regression analyses were performed to identify UC-related prognostic genes. A UC-related signature was created and confirmed using distinct datasets. Independent prognostic predictors were authenticated using Cox analysis. The Cell-type Identification by Estimating Relative Subsets of RNA Transcripts algorithm and Spearman method were applied to probe the linkage between UC-related prognostic genes and tumor immune-infiltrating cells. The Human Protein Atlas database was used to determine the protein expression levels of prognostic genes in CRC and normal tissues. Verification of the expression levels of UC-related prognostic genes in clinical tissue samples was performed using real-time quantitative polymerase chain reaction (qPCR). Results: A total of 49 DEUCRGs in CRC were mined. Eight prognostic genes (TIMP1, FABP4, MMP3, MMP1, CD177, CA2, S100P, and SPP1) were identified to construct a UC-related gene signature. The signature was then affirmed using an external validation set. The risk score was demonstrated to be a credible independent prognostic predictor using Cox regression analysis. Functional enrichment analysis revealed that focal adhesion, ECM-receptor interaction, IL-17 signaling pathway, and nitrogen metabolism were associated with the UC-related gene signature. Immune infiltration and correlation analyses revealed a significant correlation between UC-related prognostic genes and differential immune cells between the two risk subgroups. Finally, the qPCR results of clinical samples further confirmed the results of the public database. Conclusion: Taken together, this study authenticated UC-related prognostic genes and developed a gene signature for the prognosis of CRC, which will be of great significance in the identification of prognostic molecular biomarkers, clinical prognosis prediction, and development of treatment strategies for patients with CRC.

Activated Syndecan-1 shedding contributes to mice colitis induced by dextran sulfate sodium.

BACKGROUND: Syndecan-1(Sdc1) plays important roles in many steps of inflammatory responses. In ulcerative colitis patients, decreased Sdc1 expression was observed and Sdc1 analogue heparin could improve the disease course. A better understanding of how Sdc1 functions in colitis will benefit the disease intervention. AIMS: To evaluate the role of Sdc1 in dextran sulfate sodium (DSS)-induced colitis. METHODS: BALB/c mice were grouped randomly into control, DSS, and heparin+DSS. The DSS group was given 4% DSS orally and heparin+DSS group was given 4% DSS with heparin (enoxaparin) subcutaneously, while the control was given distilled water orally. All mice were killed at day 7. Disease activities, histopathological changes, membrane-bound and free Sdc1 level and mRNA expression of Sdc1, IL-1, and IL-10 in colon mucosa were detected. RESULTS: Significant colitis was observed in the DSS group, but disease activity index and histological score showed significant lower in the heparin+DSS group than those in the DSS group. Compared to the control group, decreased Sdc1 protein expression was detected in colon mucosa of DSS-induced colitis while Sdc1 ectodomain level in serum was much higher. Inhibited Sdc1 ectodomain shedding was detected in the heparin+DSS group compared to the DSS group. RT-PCR demonstrated that both IL-1 and IL-10 expression were up-regulated in DSS-induced colitis while heparin lessened the up-regulation extent. CONCLUSIONS: Sdc1 shedding is activated in DSS-induced colitis and heparin, which mimics Sdc1 functions, relieves colitis severity by inhibiting Sdc1 shedding and down-regulating cytokines expression.