Factors Associated with White Fat Browning: New Regulators of Lipid Metabolism.

Mammalian adipose tissue can be divided into white and brown adipose tissue based on its colour, location, and cellular structure. Certain conditions, such as sympathetic nerve excitement, can induce the white adipose adipocytes into a new type of adipocytes, known as beige adipocytes. The process, leading to the conversion of white adipocytes into beige adipocytes, is called white fat browning. The dynamic balance between white and beige adipocytes is closely related to the body's metabolic homeostasis. Studying the signal transduction pathways of the white fat browning might provide novel ideas for the treatment of obesity and alleviation of obesity-related glucose and lipid metabolism disorders. This article aimed to provide an overview of recent advances in understanding white fat browning and the role of BAT in lipid metabolism.

LncRNA-Mediated Adipogenesis in Different Adipocytes.

Long-chain noncoding RNAs (lncRNAs) are RNAs that do not code for proteins, widely present in eukaryotes. They regulate gene expression at multiple levels through different mechanisms at epigenetic, transcription, translation, and the maturation of mRNA transcripts or regulation of the chromatin structure, and compete with microRNAs for binding to endogenous RNA. Adipose tissue is a large and endocrine-rich functional tissue in mammals. Excessive accumulation of white adipose tissue in mammals can cause metabolic diseases. However, unlike white fat, brown and beige fats release energy as heat. In recent years, many lncRNAs associated with adipogenesis have been reported. The molecular mechanisms of how lncRNAs regulate adipogenesis are continually investigated. In this review, we discuss the classification of lncRNAs according to their transcriptional location. lncRNAs that participate in the adipogenesis of white or brown fats are also discussed. The function of lncRNAs as decoy molecules and RNA double-stranded complexes, among other functions, is also discussed.

miR-370-3p Regulates Adipogenesis through Targeting Mknk1.

Excessive fat accumulation can lead to obesity, diabetes, hyperlipidemia, atherosclerosis, and other diseases. MicroRNAs are a class of microRNAs that regulate gene expression and are highly conserved in function among species. microRNAs have been shown to act as regulatory factors to inhibit fat accumulation in the body. We found that miR-370-3p was expressed at lower levels in the fat mass of mice on a high-fat diet than in mice on a normal control diet. Furthermore, our data showed that the overexpression of miR-370-3p significantly suppressed the mRNA expression levels of adipogenic markers. Thus, miR-370-3p overexpression reduced lipid accumulation. Conversely, the inhibition of miR-370-3p suppressed 3T3-L1 preadipocyte proliferation and promoted preadipocyte differentiation. In addition, Mknk1, a target gene of miR-370-3p, plays an opposing role in preadipocyte proliferation and differentiation. Moreover, consistent results from in vitro as well as in vivo experiments suggest that the inhibition of fat accumulation by miR-370-3p may result from the inhibition of saturated fatty acids that promote the accumulation of polyunsaturated fatty acids. In conclusion, these results suggest that miR-370-3p plays an important role in adipogenesis and fatty acid metabolism through the regulation of Mknk1.

Clinical outcomes of curative treatment for colorectal liver metastases combined with cytoreductive surgery and intraperitoneal chemotherapy for peritoneal metastases: a systematic review and meta-analysis of current evidence.

BACKGROUND: The optimal treatment for colorectal cancer (CRC) with synchronous peritoneal carcinomatosis (PC) and liver metastases (LM) remains controversial. We aimed to investigate clinical outcomes in patients with CRC and concomitant PC and LM who had undergone curative surgery, including resections at both metastatic sites and synchronous intraabdominal chemotherapy. METHODS: We searched PubMed, EMBASE, and Web of Science databases for eligible studies. Studies focusing on the clinical effects of curative surgery and synchronous intraabdominal chemotherapy for patients with CRC and concomitant PC and LM were included. Meta-analysis results were recorded as hazard ratios (HRs), risk ratios (RRs) and mean differences. RESULTS: We included 9 of 998 identified studies in the meta-analysis, involving 746 patients (221 patients with PC + LM, 525 patients with PC). Overall survival (pooled HR 1.68, 95% confidence interval [CI] 1.33-2.13, p < 0.01) and disease-free survival (pooled HR 1.82, 95% CI 1.51-2.20, p < 0.01) were both lower in patients with PC + LM. A higher recurrence rate (RR 1.22, 95% CI 1.04-1.44, p = 0.02) and major postoperative morbidity (RR 1.47, 95% CI 1.19-1.82, p < 0.01) were also observed in patients with PC + LM. CONCLUSION: Liver resection in combination with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for patients with CRC and synchronous hepatic and peritoneal metastases may be associated with worse survival and higher morbidity compared with patients with isolated PC. More restricted patient inclusion criteria should be established to facilitate an optimal prognosis for this patient group.

A signature of hypoxia-related factors reveals functional dysregulation and robustly predicts clinical outcomes in stage I/II colorectal cancer patients.

BACKGROUND: The hypoxic tumor microenvironment accelerates the invasion and migration of colorectal cancer (CRC) cells. The aim of this study was to develop and validate a hypoxia gene signature for predicting the outcome in stage I/II CRC patients that have limited therapeutic options. METHODS: The hypoxic gene signature (HGS) was constructed using transcriptomic data of 309 CRC patients with complete clinical information from the CIT microarray dataset. A total of 1877 CRC patients with complete prognostic information in six independent datasets were divided into a training cohort and two validation cohorts. Univariate and multivariate analyses were conducted to evaluate the prognostic value of HGS. RESULTS: The HGS consisted of 14 genes, and demarcated the CRC patients into the high- and low-risk groups. In all three cohorts, patients in the high-risk group had significantly worse disease free survival (DFS) compared with those in the low risk group (training cohort-HR = 4.35, 95% CI 2.30-8.23, P < 0.001; TCGA cohort-HR = 2.14, 95% CI 1.09-4.21, P = 0.024; meta-validation cohort-HR = 1.91, 95% CI 1.08-3.39, P = 0.024). Compared to Oncotype DX, HGS showed superior predictive outcome in the training cohort (C-index, 0.80 vs 0.65) and the validation cohort (C-index, 0.70 vs 0.61). Pathway analysis of the high- and low-HGS groups showed significant differences in the expression of genes involved in mTROC1, G2-M, mitosis, oxidative phosphorylation, MYC and PI3K-AKT-mTOR pathways (P < 0.005). CONCLUSION: Hypoxic gene signature is a satisfactory prognostic model for early stage CRC patients, and the exact biological mechanism needs to be validated further.

Clinical utility of double-balloon enteroscopy in children: A single-centre experience in South China.

AIM: Double-balloon enteroscopy (DBE) is a useful tool for the evaluation and treatment of small bowel disease. Limited clinical data are available regarding the indications, clinical findings and safety associated with the use of DBE in children. The aim of this study is to investigate the utility and safety of DBE in children. METHODS: A total of 72 DBE procedures were performed on 61 children at the Sixth Affiliated Hospital, Sun Yat-sen University, between 1 April 2013 and 31 December 2017. The clinical data were analysed retrospectively. RESULTS: DBE was attempted 72 times in 61 children (45 boys and 16 girls) of an age range between 6 and 14 years (mean age: 11.9 years). The most common indication for DBE was occult gastrointestinal bleeding and abdominal pain. The positive rate of abnormal findings was 77.5% (55/72). Most children showed non-specific enteritis and Crohn's disease. Eight children underwent successful therapeutic enteroscopy. No serious complication was observed in any child in this case series. CONCLUSION: DBE can be a useful diagnostic and therapeutic tool for small bowel disorders in children.

Predictability of gastric intestinal metaplasia by patchy lavender color seen on linked color imaging endoscopy.

We aimed to investigate the ability of linked color imaging (LCI) versus white light endoscopy (WLE) to detect gastric intestinal metaplasia (GIM). One hundred and seven participants who underwent upper gastrointestinal endoscopy were included. Under WLE endoscopy, biopsies were performed on any suspected abnormal mucosal changes. Under LCI endoscopy, we tested whether the specific color feature of patchy lavender color (PLC) pathologically indicated GIM. Biopsies were randomly performed in participants who had neither PLC nor suspected lesions. The detection abilities of LCI and WLE were assessed by comparison of histological and endoscopic findings. A total of 41 participants had histological GIM. The total diagnostic accuracy rate for GIM by LCI was 79.44%, higher than that of WLE (40.19%) (P < 0.001). Moreover, LCI with targeted biopsies showed a significantly increased ability to detect GIM (P < 0.001). PLC observed in the gastric mucosa on LCI can guide endoscopic biopsies and increase the detection rate of GIM. Thus, LCI could be a good tool for detecting GIM. ClinicalTrials.gov Identifier: ChiCTR-DDD-17011326).

MicroRNA 26b promotes colorectal cancer metastasis by downregulating phosphatase and tensin homolog and wingless-type MMTV integration site family member 5A.

Invasion and metastasis are crucially important factors in the survival of malignant tumors. Epithelial-mesenchymal transition (EMT) is an early step in metastatic progression and the presence of cancer stem cells is closely related to tumor survival, proliferation, metastasis, and recurrence. Herein we report that ectopic overexpression of microRNA 26b (miR-26b) in colorectal cancer (CRC) cell lines promoted EMT and stem cell-like phenotypes in vitro. Furthermore, miR-26b directly targeted and suppressed multiple tumor suppressors, including phosphatase and tensin homolog (PTEN) and wingless-type MMTV integration site family member 5A (WNT5A). Notably, miR-26b is markedly upregulated in tumor samples from patients with lymphatic metastases. These results indicate that miR-26b promotes CRC metastasis by downregulating PTEN and WNT5A, and may represent a therapeutic target for metastatic CRC.

Ability of blue laser imaging with magnifying endoscopy for the diagnosis of gastric intestinal metaplasia.

We aimed to determine the utility of blue laser imaging (BLI) with magnifying endoscopy (BLI-ME) for the prediction and diagnosis of gastric intestinal metaplasia (GIM). Participants, aged between 40 and 75 years, undergoing gastroscopy from January to April 2017 were included in this study. The ability of BLI-ME and white light endoscopy (WLE) to detect GIM was assessed by comparing the endoscopic findings with the histological findings. The correlation between the grades of light blue crest (LBC) appearance and histology grade of GIM was calculated. We included 100 participants in this study. GIM was diagnosed in 27 participants; 20 participants were detected by both BLI and WLE, four by BLI only, and three exclusively by random biopsies. The values of sensitivity, specificity, positive predictive values, and negative predictive values for detecting GIM were 34.9, 38.9, 25.4, and 57.1%, respectively, for WLE and 88.9, 96.7, 94.1, and 93.3%, respectively, for BLI-ME. The diagnostic accuracy for GIM was 43% for WLE and 94.0% for BLI-ME. A good correlation between the grades of LBC and the grades of GIM on histology was observed (P < 0.01). BLI-ME achieved a good diagnostic efficiency for detection of GIM. LBC seen on BLI-ME is a typical indicator of GIM.

Overexpression of Hexokinase 1 as a poor prognosticator in human colorectal cancer.

It has been suggested that hexokinase 1 (HK1) is involved in tumorigenesis. However, the expression dynamics of HK1 and its prognostic significance in human colorectal cancer (CRC) still remain unclear. The aim of the present study was to investigate the expression of HK1 and its prognostic significance in CRC. In this study, immunohistochemical analysis was used to examine the expression dynamics of HK1 in CRC tissues from two independent cohorts. Receiver operating characteristic curve analysis, Kaplan-Meier curves, and Cox regression analysis were utilized to investigate the prognostic significance. Results showed that a high expression of HK1 was observed in 106 of 393 (27.0 %) and 69 of 229 (30.1 %) of CRC in the training cohort and validation cohort, respectively. Further correlation analyses indicated that the increased HK1 expression was strongly correlated with the pN classification and TNM stage. Both cohorts showed a close association between the overexpression of HK1 and poorer overall survival. Importantly, multivariate analysis identified HK1 expression in CRC as an independent prognostic factor. Overexpression of HK1 may act as a significant biomarker of poor prognosis for patients with CRC.

Astaxanthin Inhibits Proliferation and Induces Apoptosis and Cell Cycle Arrest of Mice H22 Hepatoma Cells.

BACKGROUND It is widely recognized that astaxanthin (ASX), a member of the carotenoid family, has strong biological activities including antioxidant, anti-inflammation, and immune-modulation activities. Previous studies have confirmed that ASX can effectively inhibit hepatoma cells in vitro. MATERIAL AND METHODS MTT was used to assay proliferation of mice H22 cells, and flow cytometry was used to determine apoptosis and cell cycle arrest of H22 cells in vitro and in vivo. Moreover, anti-tumor activity of ASX was observed in mice. RESULTS ASX inhibited the proliferation of H22 cells, promoted cell necrosis, and induced cell cycle arrest in G2 phase in vitro and in vivo. CONCLUSIONS This study indicated that ASX can inhibit proliferation and induce apoptosis and cell cycle arrest in mice H22 hepatoma cells in vitro and in vivo.

Preoperative Percutaneous Drainage of Spontaneous Intra-Abdominal Abscess in Patients With Crohn's Disease: A Meta-Analysis.

GOALS: We aimed to compare clinical outcomes between percutaneous drainage (PD) with or without further elective surgery and initial surgery for patients with Crohn's disease (CD)-related spontaneous intra-abdominal abscess. BACKGROUND: Intra-abdominal abscess is common in patients with CD leading to significant morbidity. The role of PD before abdominal surgery in patients with CD remains controversial. STUDY: We performed a meta-analysis comparing PD and surgery as the initial approach to CD-related spontaneous intra-abdominal abscess. Overall complication and recurrent abscess were assessed. Subgroup analyses on initial PD were performed including preoperative PD and PD alone. RESULTS: A total of 9 studies including 513 patients with CD-related spontaneous intra-abdominal abscesses were included. The overall complication rate was significantly higher in patients undergoing initial surgery compared with those undergoing initial PD [odds ratio (OR)=0.58; 95% confidence interval (CI), 0.35-0.96; P=0.03]. In a subgroup analysis, preoperative PD was associated with a significant reduction in overall complication (OR=0.44; 95% CI, 0.23-0.83; P=0.01) as compared with initial surgery. The risk for recurrent abscess was higher in patients who underwent PD alone than those who underwent initial surgery (OR=2.16; 95% CI, 1.03-4.54; P=0.04). No significance difference in postoperative recurrent abscess was found between preoperative PD group and initial surgery group. CONCLUSION: Although abdominal surgery appeared to be inevitable in the majority of the patients with CD who develop intra-abdominal abscess, preoperative PD may decrease overall complication after surgery.

Bone marrow mesenchymal stem cells ameliorate colitis-associated tumorigenesis in mice.

BACKGROUND AND AIMS: Bone marrow-derived mesenchymal stem cell (MSC) is widely studied in inflammatory bowel disease (IBD) in basic and clinical research. However, patients with IBD have higher risk of developing colorectal cancer and MSC has dual effect on tumorigenesis. This study aims to evaluate the role of MSC on tumorigenesis of IBD. METHODS: MSCs were isolated from the bone marrow of allogenic mice and identified by flow cytometry. Mice in the model of colitis-associated tumorigenesis induced by azoxymethane and dextran sulfate sodium were injected with MSCs. Colon length, spleen size and tumors formation were assessed macroscopically. Pro-inflammatory cytokines and STAT3 phosphorylation in colon tissues were analyzed. RESULTS: MSCs ameliorated the severity of colitis associated tumorigenesis compared with PBS control, with attenuated weight loss, longer colons and smaller spleens. Tumor number and tumor load were significantly less in the MSC group while tumor size remained comparable. Histological assessment indicated MSCs could reduce histological damage of the colon tissue. Decreased expression of pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6), and down-regulation of STAT3 phosphorylation in colon tissue were found after MSC treatment. CONCLUSION: MSCs might ameliorate the tumorigenesis of inflammatory bowel disease by suppression of expression of pro-inflammatory cytokines and STAT3 activation.

Omega-3 Polyunsaturated Fatty Acids Alleviate Intestinal Barrier Dysfunction in Obstructive Jaundice Rats.

Obstructive jaundice (OJ) can cause multiple pathophysiological consequences including intestinal barrier dysfunction. Omega-3 has been indicated to have a promising therapeutic effect on OJ. This study aimed to further investigate the functions of omega-3 on OJ-induced intestinal injury. A rat OJ model was established by bile duct ligation with or without omega-3 administration. ELISA was utilized for measuring serum levels of inflammatory cytokines. Hematoxylin-eosin staining and TUNEL staining were employed for detecting the morphological changes and cell apoptosis in rat intestine. Western blotting was utilized for evaluating expression of tight junction proteins in the intestinal tissues. Omgea-3 offset the reduction in body weight of OJ rats. Omega-3 alleviated inflammatory response, pathological damages and cell apoptosis in the intestine of OJ rats. Additionally, omega-3 enhanced levels of tight junction proteins in the intestinal tissues of OJ rats. Omega-3 ameliorates OJ-triggered impairment of intestinal barrier function in rats.

Multi-Task Learning With Hierarchical Guidance for Locating and Stratifying Submucosal Tumors.

Locating and stratifying the submucosal tumor of the digestive tract from endoscopy ultrasound (EUS) images are of vital significance to the preliminary diagnosis of tumors. However, the above problems are challenging, due to the poor appearance contrast between different layers of the digestive tract wall (DTW) and the narrowness of each layer. Few of existing deep-learning based diagnosis algorithms are devised to tackle this issue. In this article, we build a multi-task framework for simultaneously locating and stratifying the submucosal tumor. And considering the awareness of the DTW is critical to the localization and stratification of the tumor, we integrate the DTW segmentation task into the proposed multi-task framework. Except for sharing a common backbone model, the three tasks are explicitly directed with a hierarchical guidance module, in which the probability map of DTW itself is used to locally enhance the feature representation for tumor localization, and the probability maps of DTW and tumor are jointly employed to locally enhance the feature representation for tumor stratification. Moreover, by means of the dynamic class activation map, probability maps of DTW and tumor are reused to enforce the stratification inference process to pay more attention to DTW and tumor regions, contributing to a reliable and interpretable submucosal tumor stratification model. Additionally, considering the relation with respect to other structures is beneficial for stratifying tumors, we devise a graph reasoning module to replenish non-local relation knowledge for the stratification branch. Experiments on a Stomach-Esophagus and an Intestinal EUS dataset prove that our method achieves very appealing performance on both tumor localization and stratification, significantly outperforming state-of-the-art object detection approaches.

The Proinflammatory Role of Guanylate-Binding Protein 5 in Inflammatory Bowel Diseases.

NLRP3 inflammasome is implicated in the pathogenesis of inflammatory bowel diseases (IBD). Since guanylate-binding protein 5 (GBP5) induces the NLRP3 inflammasome activity, we aim to investigate the potential role of GBP5 in IBD pathogenesis. The expression of GBP5, NLRP3 inflammasome, and related cytokines and chemokines was examined in two cohorts of IBD patients and healthy controls, by microarray transcriptome analysis and quantitative real-time PCR. Cellular localization of GBP5 in colonic biopsies was examined by immunohistochemistry and immunofluorescence with confocal microscopy. For functional studies, GBP5 was induced by interferon γ or silenced by siRNA or CRISPR/CAS9 technique, and inflammatory activities were evaluated at mRNA and protein levels. We found that the expression of GBP5 was elevated in colonic mucosa in two geographically and culturally distinct IBD cohorts. In colonic tissues of IBD patients, GBP5 expression was mainly confined to immune cells and the levels of GBP5 expression were correlated with those of the inflammatory cytokines and chemokines. In cultured T and macrophage cells, the expression of proinflammatory cytokines and chemokines was increased when GBP5 was induced, while GBP5 deficiency leads to decreased expression of proinflammatory mediators including gasdermin D, caspase 1, cytokines, and chemokines. We conclude that GBP5 is required in the expression of many proinflammatory cytokines and chemokines in intestinal immune cells. In addition, GBP5 may upregulate inflammatory reactions through an inflammasome-mediated mechanism. Since GBP5 plays a proinflammatory role at the early steps of the inflammatory cascades of IBD pathogenesis, and is implicated in IBD patients of distinct genetic and environmental backgrounds, targeting GBP5 could be an effective strategy for the management of IBD.

Correlation between altered gut microbiota and elevated inflammation markers in patients with Crohn's disease.

Prior studies reported inconsistent results on the altered gut microbial composition in patients with Crohn's disease (CD), likely under the influences of many confounding factors including genetic, life style and environmental variations among different study cohorts. This study aims to examine the gut microbiota of CD patients with particular efforts to minimize the impact of the confounding factors. For this purpose, the healthy relatives of the patients were enrolled as control subjects so that the paired study subjects may have similar genetic background, dietary habits, and household environment. The fecal microbiota of the study subjects were examined by 16S rRNA sequencing. After the identification of the differential bacterial genera, multivariate regression analysis was performed to adjust the results for the impact of confounding factors. We found that the microbiota of the CD patients were featured with reduced short chain fatty acid (SCFA) producing bacteria and elevated opportunistic pathogen Escherichia-Shigella. Correlation analysis indicated that the elevation in Escherichia-Shigella and the reduction in SCFA-producing bacteria usually occur simultaneously. These differential genera exhibited a high capacity in distinguishing between CD and healthy controls achieving an area under curve of 0.89, and were correlated with the changes in inflammation related blood biochemical markers. Consistent with the reduction in SCFA-producing bacteria in CD, metabolomics analysis revealed decreased blood level of SCFAs in the patients. The differential genera identified in this study demonstrated outstanding capability to serve as diagnosis markers for CD and are potential targets for intervention.

Counterclockwise modular laparoscopic anatomical mesohepatectomy using combined glissonean pedicle (Takasaki approach) and hepatic vein-guided approaches.

Background: Although laparoscopic anatomical hepatectomy (LAH) is widely adopted today, laparoscopic anatomic mesohepatectomy (LAMH) for patients with hepatocellular carcinoma (HCC) remains technically challenging. Methods: In this study, 6 patients suffering from solitary liver tumors located in the middle lobe of the liver underwent counterclockwise modular LAMH using combined Glissonean pedicle (Takasaki approach) and hepatic vein-guided approaches. In this process, the Glissonean pedicle approach (Takasaki approach) was first used to transect the liver pedicles of segment right anterior (G58) and segment 4 (G4). Second, the hepatic vein-guided approach was performed along the umbilical fissure vein (UFV) to sever the liver parenchyma from the caudal to cranial direction, and the middle hepatic vein (MHV) and anterior fissure vein (AFV) were then disconnected at the root. Last, the hepatic vein-guided approach was once more performed along the ventral side of the right hepatic vein (RHV) to transect the liver parenchyma from the cranial to anterior direction, and the middle lobe of the liver, including the tumor, was removed completely. The entire process was applied in a counterclockwise fashion, and the exposure or transection sequence was G58, and G4, followed by UFV, MHV, AFV, and finally, the liver parenchyma along the ventral side of RHV. Results: The counterclockwise modular LAMH using combined Glissonean pedicle (Takasaki approach) and hepatic vein-guided approaches was feasible in all 6 cases. The median duration of the operation was 275 ± 35.07 min, and the mean estimated blood loss was 283.33 ml. All of the 6 patients recovered smoothly. The Clavien-Dindo Grade I-II complications rate was up to 33.33%, mainly characterized by postoperative pain and a small amount of ascites. No Clavien-Dindo Grade III-V complications occurred, and the mean postoperative hospital stay was 6.83 ± 1.47 days. Follow-up results showed that the average disease-free survival (DFS) was 12.17 months, and the 21-months OS rate, DFS rate and tumor recurrent rate were 100%, 83.33% and 16.67% respectively. Conclusions: Counterclockwise modular LAMH using combined Glissonean pedicle (Takasaki approach) and hepatic vein-guided approaches takes the advantages of the two approaches, is a novel protocol for LAMH. It is thought to be technically feasible for patients with a centrally located solitary HCC. The oncologic feasibility of this technique needs to be investigated based on long-term follow-up. A multicenter, large-scale, more careful study is necessary.

IBD Subtype-Regulators IFNG and GBP5 Identified by Causal Inference Drive More Intense Innate Immunity and Inflammatory Responses in CD Than Those in UC.

Background: The pathological differences between Crohn's disease (CD) and ulcerative colitis (UC) are substantial and unexplained yet. Here, we aimed to identify potential regulators that drive different pathogenesis of CD and UC by causal inference analysis of transcriptome data. Methods: Kruskal-Wallis and Dunnett's tests were performed to identify differentially expressed genes (DEGs) among CD patients, UC patients, and controls. Subsequently, differentially expressed pathways (DEPs) between CD and UC were identified and used to construct the interaction network of DEPs. Causal inference was performed to identify IBD subtype-regulators. The expression of the subtype-regulators and their downstream genes was validated by qRT-PCR with an independent cohort. Results: Compared with the control group, we identified 1,352 and 2,081 DEGs in CD and UC groups, respectively. Multiple DEPs between CD and UC were closely related to inflammation-related pathways, such as NOD-like receptor signaling, IL-17 signaling, and chemokine signaling pathways. Based on the priori interaction network of DEPs, causal inference analysis identified IFNG and GBP5 as IBD subtype-regulators. The results with the discovery cohort showed that the expression level of IFNG, GBP5, and NLRP3 was significantly higher in the CD group than that in the UC group. The regulation relationships among IFNG, GBP5, and NLRP3 were confirmed with transcriptome data from an independent cohort and validated by qRT-PCR. Conclusion: Our study suggests that IFNG and GBP5 were IBD subtype-regulators that trigger more intense innate immunity and inflammatory responses in CD than those in UC. Our findings reveal pathomechanical differences between CD and UC that may contribute to personalized treatment for CD and UC.

Crohn's disease patients with L4-esophagogastroduodenal phenotype is associated with a better prognosis: A retrospective cohort study.

Background: In the Montreal classification, L4 Crohn's disease (CD) is defined as an ileal disease, including L4-esophagogastric duodenum (EGD), L4-jejunum, and L4-proximal ileal involvement. According to the previous studies, the prognosis of L4 disease was worse than that of non-L4 disease. Among L4 diseases, the phenotypes of L4-jejunum and L4-proximal ileum indicated that the risk of abdominal surgery was higher. However, the prognosis of L4-esophagogastroduodenal remains largely elusive. Therefore, we aim to investigate whether the prognosis differs between CD patients with and without esophagogastroduodenal involvement. Methods: In this study, patients with L4-EGD phenotype (n = 74) who underwent gastroscopy, ileocolonoscopy, biopsies, and CTE from 2018 to 2020 were compared with L4 non-EGD controls (n = 148) who were randomly selected at a ratio of 1:2 in the same period. Demographic information inclusive of disease conduct and location, important points of the surgery, and hospitalization have been collected. The distinction between L4-EGD patients and non-L4-EGD patients was identified by way of multivariable logistic regression analysis. The Kaplan-Meier technique was used to consider the possibility of abdominal surgical operation and complications, observed by means of Cox percentage hazard fashions to decide if L4 EGD independently estimated the endpoints inclusive of the abdominal surgery and the occurrences of complications. Results: L4-EGD group (n = 74) had a lower proportion of intestinal fistula than the control group (n = 148) (17.6% versus 34.5%; p = 0.009), and the probabilities of requiring abdominal surgery and multiple abdominal surgeries were also lower (21.6% versus 36.5%; p = 0.025), (6.8% versus 18.9%; p = 0.016), respectively. The frequency of hospitalization was lower in the L4-EGD group than in the control group (3-7 versus 4-9; p = 0.013). L4-EGD phenotype was found to be an independent protective factor for abdominal surgery and intestinal fistula in the Cox regression model, with HRs of 0.536 (95%CI: 0.305-0.940; p = 0.030) and 0.478 (95%CI: 0.259-0.881; p = 0.018), respectively. Conclusion: Our data suggest that the L4-EGD phenotype may have a better prognosis compared to the Non-L4-EGD phenotype. Our data may advocate a revision of the Montreal classification including separate designations for L4-EGD disease.