Publications by authors named "Minhu Chen"

204 Publications

Reverse translation approach generates a signature of penetrating fibrosis in Crohn's disease that is associated with anti-TNF response.

Gut 2021 Jul 14. Epub 2021 Jul 14.

Inflammation and Immunity, Cleveland Clinic, Cleveland, Ohio, USA

Objective: Fibrosis is a common feature of Crohn's disease (CD) which can involve the mesenteric fat. However, the molecular signature of this process remains unclear. Our goal was to define the transcriptional signature of mesenteric fibrosis in CD subjects and to model mesenteric fibrosis in mice to improve our understanding of CD pathogenesis.

Design: We performed histological and transcriptional analysis of fibrosis in CD samples. We modelled a CD-like fibrosis phenotype by performing repeated colonic biopsies in mice and analysed the model by histology, type I collagen-targeted positron emission tomography (PET) and global gene expression. We generated a gene set list of essential features of mesenteric fibrosis and compared it to mucosal biopsy datasets from inflammatory bowel disease patients to identify a refined gene set that correlated with clinical outcomes.

Results: Mesenteric fibrosis in CD was interconnected to areas of fibrosis in all layers of the intestine, defined as penetrating fibrosis. We found a transcriptional signature of differentially expressed genes enriched in areas of the mesenteric fat of CD subjects with high levels of fibrosis. Mice subjected to repeated colonic biopsies showed penetrating fibrosis as shown by histology, PET imaging and transcriptional analysis. Finally, we composed a composite 24-gene set list that was linked to inflammatory fibroblasts and correlated with treatment response.

Conclusion: We linked histopathological and molecular features of CD penetrating fibrosis to a mouse model of repeated biopsy injuries. This experimental system provides an innovative approach for functional investigations of underlying profibrotic mechanisms and therapeutic concepts in CD.
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http://dx.doi.org/10.1136/gutjnl-2020-323405DOI Listing
July 2021

Index-Based Dietary Patterns and Inflammatory Bowel Disease: A Systematic Review of Observational Studies.

Adv Nutr 2021 Jun 22. Epub 2021 Jun 22.

Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Diet is one of the most critical factors for inflammatory bowel disease (IBD). A whole dietary pattern should be considered when doing nutrient-based research to preserve the potential for synergism between nutrients. Dietary indices are important tools to evaluate diet quality, and we investigated the associations of it with IBD. Fourteen studies on the relation between index-based dietary patterns and IBD were included. 6 studies showed the relation between index-based dietary patterns and IBD risk, 7 studies explored the dietary indices and progression of IBD, and 1 study investigated the relationship between index and all-cause mortality in IBD patients. These results implied that a high score on the Mediterranean diet was negatively associated with risk and progression of IBD. However, a diet with high inflammatory potential could increase risk and aggravate disease activity in IBD. Dietary scores have the potential to evaluate the association between overall diet quality and risk and progression of IBD. Future randomized controlled trials are required to confirm the effect of the change in dietary score. This review was registered at www.crd.york.ac.uk/prospero/ as CRD42020220926.
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http://dx.doi.org/10.1093/advances/nmab069DOI Listing
June 2021

The emerging role of ferroptosis in intestinal disease.

Cell Death Dis 2021 03 17;12(4):289. Epub 2021 Mar 17.

Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China.

Ferroptosis is a newly recognised type of regulated cell death (RCD) characterised by iron-dependent accumulation of lipid peroxidation. It is significantly distinct from other RCDs at the morphological, biochemical, and genetic levels. Recent reports have implicated ferroptosis in multiple diseases, including neurological disorders, kidney injury, liver diseases, and cancer. Ferroptotic cell death has also been associated with dysfunction of the intestinal epithelium, which contributes to several intestinal diseases. Research on ferroptosis may provide a new understanding of intestinal disease pathogenesis that benefits clinical treatment. In this review, we provide an overview of ferroptosis and its underlying mechanisms, then describe its emerging role in intestinal diseases, including intestinal ischaemia/reperfusion (I/R) injury, inflammatory bowel disease (IBD), and colorectal cancer (CRC).
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http://dx.doi.org/10.1038/s41419-021-03559-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969743PMC
March 2021

Can fecal calprotectin accurately identify histological activity of ulcerative colitis? A meta-analysis.

Therap Adv Gastroenterol 2021 27;14:1756284821994741. Epub 2021 Feb 27.

Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan 2nd Road, Guangzhou 510080, Guangdong Province, P.R. China.

Background And Aims: Elevated fecal calprotectin (FC) levels have been reported to correlate with histological activity in patients with ulcerative colitis (UC). However, the accuracy of FC for evaluating histological activity of UC remains to be determined. The aim of this study was to determine the accuracy of FC for evaluating histological activity of UC, based on updated definitions.

Methods: Related studies were retrieved from the PubMed, Web of Science, Embase, and Cochrane databases. Adult participants diagnosed with UC were included when sufficient data could be extracted to calculate the accuracy of FC for evaluating histological activity. The primary outcome was histological response, and the secondary outcome was histological remission, defined according to a recently updated position paper of European Crohn's and Colitis Organization. Statistics were pooled using bivariate mixed-effects models. The area under the curve was estimated by summary receiver-operating characteristic curves.

Results: Nine studies were included, from which 1039 patients were included for the analysis of histological response and 591 patients for histological remission. For the evaluation of histological response, the pooled sensitivity, specificity, and the area under the curve were 0.69 [95% confidence interval (CI): 0.52-0.82], 0.77 (95% CI: 0.63-0.87), and 0.80 (95% CI: 0.76-0.83), respectively. For the evaluation of histological remission, the corresponding estimates were 0.76 (95% CI: 0.71-0.81), 0.71 (95% CI: 0.62-0.78), and 0.79 (95% CI: 0.75-0.82), respectively. FC had a higher accuracy in studies using Nancy Index. For histological response, the cut-off values of FC ranged from 50 to 172 µg/g, and the sensitivity was higher in studies with FC cut-off values >100 µg/g (0.77 0.65).

Conclusion: FC is a valuable biomarker for assessing histological activity in patients with UC. A cut-off value of 100-200 µg/g is more appropriate to spare patients from an unnecessary endoscopy and biopsy.
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http://dx.doi.org/10.1177/1756284821994741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923968PMC
February 2021

MALAT1 maintains the intestinal mucosal homeostasis in Crohn's disease via the miR-146b-5p-CLDN11/NUMB pathway.

J Crohns Colitis 2021 Mar 2. Epub 2021 Mar 2.

Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P.R. China.

Background & Aims: Intestinal homeostasis disorder is critical for developing Crohn's disease (CD). Maintaining mucosal barrier integrity is essential for intestinal homeostasis, preventing intestinal injury and complications. Among the remarkably altered long non-coding RNAs (lncRNAs) in CD, we aimed to investigate whether metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) modulated CD and consequent disruption of intestinal homeostasis.

Methods: Microarray analyses on intestinal mucosa of CD patients and controls were performed to identify dysregulated lncRNAs. MALAT1 expression was investigated via qRT-PCR and its distribution in intestinal tissues was detected using BaseScope. Intestines from MALAT1 knockout mice with colitis were investigated using histological, molecular and biochemical approaches. Effects of intestinal epithelial cells transfected with MALAT1 lentiviruses and Smart Silencer, on monolayer permeability and apical junction complex (AJC) proteins were analysed. MiR-146b-5p were confirmed as a critical MALAT1 mediator in cells transfected with miR-146b-5p mimic/inhibitor and in colitis mice administered with agomir-146b-5p/antagomir-146b-5p. Interaction between MALAT1 and miR-146b-5p was predicted via bioinformatics and validated using Dual-luciferase reporter assay and Ago2-RIP.

Results: MALAT1 was aberrantly downregulated in the intestine mucosa of CD patients and mice with experimental colitis. MALAT1 knockout mice were hypersensitive to DSS-induced experimental colitis. MALAT1 regulated intestinal mucosal barrier and regained intestinal homeostasis by sequestering miR-146b-5p and maintaining the expression of the AJC proteins NUMB and CLDN11.

Conclusions: Downregulation of MALAT1 contributed to the pathogenesis of CD by disrupting AJC. Thus, a specific MALAT1-miR-146b-5p-NUMB/CLDN11 pathway that plays a vital role in maintaining intestinal mucosal homeostasis may serve as a novel target for CD treatment.
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http://dx.doi.org/10.1093/ecco-jcc/jjab040DOI Listing
March 2021

Therapeutic Interleukin-6 Trans-signaling Inhibition by Olamkicept (sgp130Fc) in Patients With Active Inflammatory Bowel Disease.

Gastroenterology 2021 Jun 2;160(7):2354-2366.e11. Epub 2021 Mar 2.

Institute of Clinical Molecular Biology, Kiel University and University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany. Electronic address:

Background & Aims: A large unmet therapeutic need exists in inflammatory bowel disease (IBD). Inhibition of interleukin (IL)-6 appears to be effective, but the therapeutic benefit of a complete IL6/IL6 receptor (IL6R) blockade is limited by profound immunosuppression. Evidence has emerged that chronic proinflammatory activity of IL6 is mainly mediated by trans-signaling via a complex of IL6 bound to soluble IL6R engaging the gp130 co-receptor without the need for membrane-bound IL6R. We have developed a decoy protein, sgp130Fc, that exclusively blocks IL6 proinflammatory trans-signaling and has shown efficacy in preclinical models of IBD, without signs of immunosuppression.

Methods: We present a 12-week, open-label, prospective phase 2a trial (FUTURE) in 16 patients with active IBD treated with the trans-signaling inhibitor olamkicept (sgp130Fc) to assess the molecular mechanisms, safety, and effectiveness of IL6 trans-signaling blockade in vivo. We performed in-depth molecular profiling at various timepoints before and after therapy induction to identify the mechanism of action of olamkicept.

Results: Olamkicept was well tolerated and induced clinical response in 44% and clinical remission in 19% of patients. Clinical effectiveness coincided with target inhibition (reduction of phosphorylated STAT3) and marked transcriptional changes in the inflamed mucosa. An olamkicept-specific transcriptional signature, distinguishable from remission signatures of anti-tumor necrosis factor (infliximab) or anti-integrin (vedolizumab) therapies was identified.

Conclusions: Our data suggest that blockade of IL6 trans-signaling holds great promise for the therapy of IBD and should undergo full clinical development as a new immunoregulatory therapy for IBD. (EudraCT no., Nu 2016-000205-36).
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http://dx.doi.org/10.1053/j.gastro.2021.02.062DOI Listing
June 2021

Development and Validation of a Novel Computed-Tomography Enterography Radiomic Approach for Characterization of Intestinal Fibrosis in Crohn's Disease.

Gastroenterology 2021 Jun 17;160(7):2303-2316.e11. Epub 2021 Feb 17.

Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China. Electronic address:

Background & Aims: No reliable method for evaluating intestinal fibrosis in Crohn's disease (CD) exists; therefore, we developed a computed-tomography enterography (CTE)-based radiomic model (RM) for characterizing intestinal fibrosis in CD.

Methods: This retrospective multicenter study included 167 CD patients with 212 bowel lesions (training, 98 lesions; test, 114 lesions) who underwent preoperative CTE and bowel resection at 1 of the 3 tertiary referral centers from January 2014 through June 2020. Bowel fibrosis was histologically classified as none-mild or moderate-severe. In the training cohort, 1454 radiomic features were extracted from venous-phase CTE and a machine learning-based RM was developed based on the reproducible features using logistic regression. The RM was validated in an independent external test cohort recruited from 3 centers. The diagnostic performance of RM was compared with 2 radiologists' visual interpretation of CTE using receiver operating characteristic (ROC) curve analysis.

Results: In the training cohort, the area under the ROC curve (AUC) of RM for distinguishing moderate-severe from none-mild intestinal fibrosis was 0.888 (95% confidence interval [CI], 0.818-0.957). In the test cohort, the RM showed robust performance across 3 centers with an AUC of 0.816 (95% CI, 0.706-0.926), 0.724 (95% CI, 0.526-0.923), and 0.750 (95% CI, 0.560-0.940), respectively. Moreover, the RM was more accurate than visual interpretations by either radiologist (radiologist 1, AUC = 0.554; radiologist 2, AUC = 0.598; both, P < .001) in the test cohort. Decision curve analysis showed that the RM provided a better net benefit to predicting intestinal fibrosis than the radiologists.

Conclusions: A CTE-based RM allows for accurate characterization of intestinal fibrosis in CD.
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http://dx.doi.org/10.1053/j.gastro.2021.02.027DOI Listing
June 2021

Gut Microbiota Profile in Pediatric Patients With Inflammatory Bowel Disease: A Systematic Review.

Front Pediatr 2021 2;9:626232. Epub 2021 Feb 2.

Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Accumulating evidence have implicated gut microbiota alterations in pediatric and adult patients with inflammatory bowel disease (IBD); however, the results of different studies are often inconsistent and even contradictory. It is believed that early changes in new-onset and treatment-naïve pediatric patients are more informative. We performed a systematic review to investigate the gut microbiota profiles in pediatric IBD and identify specific microbiota biomarkers associated with this disorder. Electronic databases were searched from inception to 31 July 2020 for studies that observed gut microbiota alterations in pediatric patients with IBD. Study quality was assessed using the Newcastle-Ottawa scale. A total of 41 original studies investigating gut microbiota profiles in pediatric patients with IBD were included in this review. Several studies have reported a decrease in α-diversity and an overall difference in β-diversity. Although no specific gut microbiota alterations were consistently reported, a gain in and a significant decrease in , and were found in the majority of the included articles. Moreover, there is insufficient data to show specific microbiota bacteria associated with disease activity, location, and behavior in pediatric IBD. This systematic review identified evidence for differences in the abundance of some bacteria in pediatric patients with IBD when compared to patients without IBD; however, no clear overall conclusion could be drawn from the included studies due to inconsistent results and heterogeneous methodologies. Further studies with large samples that follow more rigorous and standardized methodologies are needed.
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http://dx.doi.org/10.3389/fped.2021.626232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884334PMC
February 2021

Gut Microbiota Profiles and Microbial-Based Therapies in Post-operative Crohn's Disease: A Systematic Review.

Front Med (Lausanne) 2020 28;7:615858. Epub 2021 Jan 28.

Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Gut microbiota recolonization after intestinal resection had been reported to be associated with post-operative recurrence in Crohn's disease (CD). However, the results of different studies are inconsistent and even contradictory. In addition, knowledge on the efficacy of microbial-based therapies in preventing post-operative recurrence of CD is limited. Therefore, the aim of this review was to investigate gut microbiota profiles in patients with CD before and after surgery and evaluate microbial-based therapies in preventing post-operative recurrence. Electronic databases were searched from inception to 31 June 2020 using predefined terms. Studies that investigated gut microbiota pre- and post-intestinal resection, and microbial-based therapies in preventing post-operative recurrence, were eligible. Study quality was assessed using either the Newcastle-Ottawa scale or Jadad scoring system. Twelve studies investigating gut microbiota of CD patients suffering from operation, and other 12 studies evaluating the efficacy of antibiotics and probiotics, were included in our review. The mucosa-associated microbiota in surgical biopsy of CD patients is significantly distinct from that in normal mucosa from healthy subjects. Gut microbiota recolonization following surgery might be associated with post-operative recurrence in CD patients. Furthermore, CD patients with post-operative recurrence presented a gain in pro-inflammatory pathogenic bacteria and a loss in short-chain fatty acid-producing bacteria before and after surgery. However, no consistent bacteria or metabolites were found to predict the post-operative recurrence of CD. Additionally, microbial-based therapies are deficient and present restricted widespread clinical utility due to several deficiencies. Recurrence-associated bacteria observed pre- and post- operation might be promising in preventing the post-operative recurrence of CD. Furthermore, potential microbe biomarkers for predicting subsequent disease recurrence should be validated with larger sample sizes using more rigorous and standardized methodologies.
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http://dx.doi.org/10.3389/fmed.2020.615858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876235PMC
January 2021

Activated intestinal muscle cells promote preadipocyte migration: a novel mechanism for creeping fat formation in Crohn's disease.

Gut 2021 Jan 19. Epub 2021 Jan 19.

Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA

Objective: Creeping fat, the wrapping of mesenteric fat around the bowel wall, is a typical feature of Crohn's disease, and is associated with stricture formation and bowel obstruction. How creeping fat forms is unknown, and we interrogated potential mechanisms using novel intestinal tissue and cell interaction systems.

Design: Tissues from normal, UC, non-strictured and strictured Crohn's disease intestinal specimens were obtained. The muscularis propria matrisome was determined via proteomics. Mesenteric fat explants, primary human preadipocytes and adipocytes were used in multiple ex vivo and in vitro cell migration systems on muscularis propria muscle cell derived or native extracellular matrix. Functional experiments included integrin characterisation via flow cytometry and their inhibition with specific blocking antibodies and chemicals.

Results: Crohn's disease muscularis propria cells produced an extracellular matrix scaffold which is in direct spatial and functional contact with the immediately overlaid creeping fat. The scaffold contained multiple proteins, but only fibronectin production was singularly upregulated by transforming growth factor-β1. The muscle cell-derived matrix triggered migration of preadipocytes out of mesenteric fat, fibronectin being the dominant factor responsible for their migration. Blockade of α5β1 on the preadipocyte surface inhibited their migration out of mesenteric fat and on 3D decellularised intestinal tissue extracellular matrix.

Conclusion: Crohn's disease creeping fat appears to result from the migration of preadipocytes out of mesenteric fat and differentiation into adipocytes in response to an increased production of fibronectin by activated muscularis propria cells. These new mechanistic insights may lead to novel approaches for prevention of creeping fat-associated stricture formation.
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http://dx.doi.org/10.1136/gutjnl-2020-323719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286985PMC
January 2021

Platelet-to-lymphocyte percentage ratio index: a simple non-invasive index to monitor the endoscopic activity in Crohn's disease.

Therap Adv Gastroenterol 2020 21;13:1756284820979442. Epub 2020 Dec 21.

Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan Road 2, Guangzhou 510080, P.R. China.

Background: Recent evidence has shown that the complete blood count (CBC) is abnormal in patients with Crohn's disease (CD). We aimed to investigate an effective CBC parameter and explore its impact on disease activity in a large CD cohort.

Methods: We performed a retrospective analysis of patients with established CD who underwent clinically indicated endoscopy at four tertiary centres in China between 2016 and 2020. Individual variables of the Simple Endoscopic Score for CD, CBC parameters, C-reactive protein (CRP) levels, erythrocyte sedimentation rate, and faecal calprotectin (FC) were independently reviewed by different investigators. The hold-out method was used to verify the predictive power of the established model.

Results: Data from a total of 1388 endoscopic procedures performed for 882 eligible CD patients were available with routine blood parameters and related indicators. The model using platelet-to-lymphocyte percentage ratio (PLpR) had high accuracy for identifying patients in endoscopic remission (ER), with an area under the curve (AUC) of 0.785 [95% confidence interval (CI): 0.784-0.787], which was comparable with that for CRP (AUC: 0.775, 95% CI: 0.774-0.777). Notably, the AUC of PLpR was significantly higher than that of CRP in patients with colonic disease and with a history of surgery. Moreover, after combining the FC with PLpR, the AUC value of FC + PLpR increased up to 0.892 (95% CI: 0.890-0.894) for identifying ER.

Conclusions: We explored an index (PLpR) to identify CD patients in ER based on platelet and lymphocyte percentage from the CBC. PLpR helped evaluate the degree of disease activity and monitor the therapeutic response.
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http://dx.doi.org/10.1177/1756284820979442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758565PMC
December 2020

Alterations in Bile Acid Metabolism Associated With Inflammatory Bowel Disease.

Inflamm Bowel Dis 2021 Jan 5. Epub 2021 Jan 5.

Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.

Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder closely related to gut dysbiosis, which is associated with alterations in an important bacterial metabolite, bile acids (BAs). Although certain findings pertinent to BA changes in IBD vary among studies owing to the differences in sample type, quantitated BA species, study methodology, and patient characteristics, a specific trend concerning variations of BAs in IBD has been identified. In elaborating on this observation, it was noted that primary BAs and conjugated BAs are augmented in fecal samples but there is a reduction in secondary BAs in fecal samples. It is not entirely clear why patients with IBD manifest these changes and what role these changes play in the onset and development of IBD. Previous studies have shown that IBD-associated BA changes may be caused by alterations in BA absorption, synthesis, and bacterial modification. The complex relationship between bacteria and BAs may provide additional and deeper insight into host-gut microbiota interactions in the pathogenesis of IBD. The characteristic BA changes may generate profound effects in patients with IBD by shaping the gut microbiota community, affecting inflammatory processes, causing BA malabsorption associated with diarrhea, and even leading to intestinal dysplasia and cancer. Thus, therapeutic strategies correcting the alterations in the composition of BAs, including the elimination of excess BAs and the supplementation of deficient BAs, may prove promising in IBD.
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http://dx.doi.org/10.1093/ibd/izaa342DOI Listing
January 2021

Targeted versus universal tuberculosis chemoprophylaxis in 1968 patients with inflammatory bowel disease receiving anti-TNF therapy in a tuberculosis endemic region.

Aliment Pharmacol Ther 2021 02 12;53(3):390-399. Epub 2020 Dec 12.

Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou, China.

Background: Anti-tumour necrosis factor (anti-TNF) therapy increases the risk of tuberculosis (TB). Given limitations of screening techniques, it remains uncertain if patients receiving anti-TNF in TB endemic regions should be screened for latent infection with chemoprophylaxis restricted to those with proven infection, or if all patients should receive chemoprophylaxis.

Aims: To compare the incidence of active TB with infliximab (IFX) following targeted and universal TB chemoprophylaxis, and to determine the rates of adverse events (AE) related to TB chemoprophylaxis METHODS: A multi-centre retrospective cohort study was performed at 18 hospitals in China of 1968 adult patients with IBD receiving IFX from 2009 to 2017. TB screening prior to IFX was performed with chest X-ray and/or computed tomography [CT] and immune reactivity testing (interferon-γ release assay and/or tuberculin skin test). Patients were followed-up for a minimum of 3 months after IFX discontinuation, or until last hospital visit if IFX therapy was ongoing. Targeted strategy was defined as TB chemoprophylaxis only for patients with a positive latent TB screen, with universal strategy defined as TB chemoprophylaxis for all patients.

Results: Mean follow-up was 1.07 ± 0.87 years with a total follow-up of 2102 patient-years. There were 1433 patients in the targeted and 483 patients in the universal TB chemoprophylaxis groups, with no significant difference in the incidence rates of active TB between groups (673.3 per 100 000 population per year vs 891.5 per 100 000 population per year, P = 0.60). In the targeted group, 55/1433 patients received TB chemoprophylaxis compared with 483/483 in the universal group, with significantly fewer AEs related to TB chemoprophylaxis in the targeted compared to the universal group (0.35% (5/1433) vs 6.8% (33/483), P < 0.05).

Conclusions: In this study of patients receiving IFX in a TB endemic area, universal chemoprophylaxis was not associated with a reduced risk of active TB when compared to a targeted chemoprophylaxis strategy, and AEs were more common. This supports the use of targeted TB chemoprophylaxis when anti-TNF therapy is initiated in TB endemic regions.
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http://dx.doi.org/10.1111/apt.16130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839545PMC
February 2021

Thalidomide Combined With Azathioprine as Induction and Maintenance Therapy for Azathioprine-Refractory Crohn's Disease Patients.

Front Med (Lausanne) 2020 6;7:557986. Epub 2020 Nov 6.

Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

The combination therapy of thalidomide and azathioprine (AZA) offers an alternative in clinical practice for Crohn's disease (CD) patients experiencing a loss of response to AZA monotherapy. However, little is known about the efficacy and safety of this combination therapy for patients with CD. This was a retrospective study of 122 consecutive CD patients who lost response to AZA therapy and had switched to a combination therapy of thalidomide and AZA. The primary outcomes were clinical response and clinical remission rates at week 24. Patients who had an initial response to combination therapy were continued on the treatment for remission maintenance. The secondary outcomes were the proportion of clinical relapse throughout maintenance. The Kaplan-Meier method was used to calculate cumulative rates, and Cox regression analysis was used for multivariate analysis. During induction, 80.3% (98/122) patients achieved clinical response within a median duration of 6.5 weeks, (interquartile range, 4.3-8.1 weeks). The rate of clinical remission at 24 weeks was 70.5%. During follow-up, 22.4% (22/98) of the patients that were maintained on combination therapy experienced clinical relapse. The proportions of patients in remission status at 12, 24, and 36 months were 85.1, 78.3, and 70.1%, respectively. Multivariate analysis revealed C-reactive protein >10 mg/L at disease relapse on AZA monotherapy [adjusted hazard ratio (HR), 4.72; 95% CI, 1.19-18.75, = 0.027] and 6-thioguanine nucleotides level ≥235 pmol/8 × 10 erythrocytes at AZA monotherapy (adjusted HR, 5.32; 95% CI, 1.40-20.14, = 0.014) were associated with disease relapse on combination therapy. The endoscopic remission rate was 63.6%. Mucosal healing was achieved in 23.6% of the patients. Both Crohn's Disease Endoscopic Index of Severity (13.4 ± 4.92 . 6.12 ± 5.24, < 0.001) and Rutgeerts scores (3.23 ± 0.73 . 1.77 ± 1.59, = 0.003) were significantly decreased with the use of combination therapy. Adverse events occurred in 62 (50.8%) patients, but only 13 (10.7%) necessitated therapy discontinuation. Thalidomide combined with AZA was effective in inducing clinical remission and sustaining long-term steroid-free remission in CD patients who lost response to AZA monotherapy.
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http://dx.doi.org/10.3389/fmed.2020.557986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677527PMC
November 2020

DNA Damage-Regulated Autophagy Modulator 1 (DRAM1) Mediates Autophagy and Apoptosis of Intestinal Epithelial Cells in Inflammatory Bowel Disease.

Dig Dis Sci 2020 Nov 13. Epub 2020 Nov 13.

Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan II Road, Guangzhou, 510080, People's Republic of China.

Background And Aims: DNA damage-regulated autophagy modulator 1 (DRAM1) is required for induction of autophagy and apoptosis. However, the influence of DRAM1 on the pathogenesis of inflammatory bowel disease (IBD) has not been explored.

Methods: DRAM1 expression was examined in the intestinal mucosa of patients with IBD and colons of colitis mice. We used a recombinant adeno-associated virus carrying small hairpain DRAM1 to knock down the DRAM1 gene to treat colitis in the mice. The effect of DRAM1 on autophagy and apoptosis of intestinal epithelial cells was explored. DRAM1-mediated interaction with the c-Jun N-terminal kinase (JNK) pathway was also examined.

Results: DRAM1 expression in the intestinal mucosa of the IBD patients was higher than that in the control participates. DRAM1 expression in the inflammatory cells in patients with Crohn's disease (CD) was lower than that in patients with ulcerative colitis (UC). Additionally, DRAM1 expression was correlated with the Simple Endoscopic Score for CD and the Mayo endoscopic score for UC. Serum levels of DRAM1 in the IBD group were substantially higher than those in the normal group. The knockdown of DRAM1 could alleviate colitis symptoms in mice. In in vitro experiments, knocking down DRAM1 could reduce autophagy and apoptosis levels. Mechanistically, DRAM1 may participate in the regulation of these two processes by positively regulating JNK activation.

Conclusions: During intestinal inflammation, the upregulation of DRAM1 may promote the activation of JNK and further aggravate intestinal epithelium damage.
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http://dx.doi.org/10.1007/s10620-020-06697-2DOI Listing
November 2020

Concordance Between the Ki-67 Index Cutoff Value of 55% and Differentiation in Neuroendocrine Tumor and Neuroendocrine Carcinoma in Grade 3 Pancreatic Neuroendocrine Neoplasms.

Pancreas 2020 Nov/Dec;49(10):1378-1382

Department of Gastroenterology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou.

Objective: In 2017 and 2019, the World Health Organization defined grade 3 neuroendocrine tumors (G3 NETs) and neuroendocrine carcinoma (G3 NEC) in the pancreas. The validity of this classification remains to be verified.

Methods: Clinical data were collected and analyzed for 39 G3 pancreatic neuroendocrine neoplasms (PanNENs) patients between 2009 and 2018.

Results: The tumor-node-metastasis stage (P = 0.0260), differentiation (P = 0.0115), and Ki-67 index (P = 0.0371) are prognostic factors for G3 PanNENs by Kaplan-Meier survival analysis. Among 39 patients, 18 had a Ki-67 index of less than 55% and well-differentiated morphology (G3 NET) and 16 had a Ki-67 index of 55% or greater and poorly differentiated morphology (G3 NEC). Grade 3 neuroendocrine tumor had a significant better prognosis than G3 NEC (median overall survival time, 25 months [95% confidence interval, 10.854-39.146 months] vs 12 months [95% confidence interval, 6.316-17.684 months], P = 0.0164). Based on Cox regression analyses, tumor-node-metastasis stage (P = 0.016) was identified as the independent prognostic factor for G3 PanNENs.

Conclusions: The upper Ki-67 index cutoff of 55% might be the best cutoff value to define G3 NETs and G3 NECs for G3 PanNENs. The World Health Organization 2017 and 2019 classification system for G3 PanNENs can identify high-risk patients with G3 PanNENs.
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http://dx.doi.org/10.1097/MPA.0000000000001693DOI Listing
October 2020

Fecal Microbiota Alterations Associated With Clinical and Endoscopic Response to Infliximab Therapy in Crohn's Disease.

Inflamm Bowel Dis 2020 10;26(11):1636-1647

Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.

Background: Gut microbiota dysbiosis is associated with the occurrence and development of Crohn disease (CD). Currently, infliximab (IFX) is used more and more to treat CD; however, gut microbiota alterations during IFX therapy are variable and sometimes even contradictory. We longitudinally identified microbial changes during IFX therapy associated with the clinical and endoscopic response to IFX treatment in CD.

Methods: Fecal-associated microbiota was analyzed using 16S sequencing in 49 patients with active CD who were prospectively recruited at baseline, week 6, and week 30, respectively. Moreover, a model trained on the gut microbiota alterations at week 6 was developed to investigate their potential to predict clinical and endoscopic responses to IFX therapy at weeks 14 and 30.

Results: Characteristics of fecal microbiota composition in patients with CD after IFX treatment displayed an increased diversity and richness, a significant gain in short-chain fatty acid -producing bacteria, and a loss of pathogenic bacteria. Furthermore, certain functional profiles of Kyoto Encyclopedia of Genes and Genomes pathways were predictably altered during the treatment period. Increased proportions of Lachnospiraceae and Blautia were associated with IFX efficacy; the combined increase of these taxa at week 6 showed 83.4% and 84.2% accuracy in predicting clinical response at weeks 14 and 30, respectively, with a predictive value of 89.1% in predicting endoscopic response at week 30.

Conclusions: We found that IFX diminished CD-related gut microbial dysbiosis by modifying microbiota composition and function. Specifically, increased Lachnospiraceae and Blautia at week 6 are associated with the clinical and endoscopic response to IFX, providing potentially predictive biomarkers for IFX treatment decision-making.
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http://dx.doi.org/10.1093/ibd/izaa253DOI Listing
October 2020

Myeloid-derived suppressor cells in gastroenteropancreatic neuroendocrine neoplasms.

Endocrine 2021 01 3;71(1):242-252. Epub 2020 Oct 3.

Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Background: Expanded myeloid-derived suppressor cells (MDSCs) correlate with disseminated metastases and poor prognosis in various human cancers. However, the role of MDSCs in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) is still unknown. We investigated the distribution of MDSCs and their clinical significance in patients with GEP-NENs.

Methods: Peripheral blood mononuclear cells (PBMCs) and paraffin-embedded tumor tissues were acquired from patients with GEP-NENs. Multicolor flow cytometry was performed to determine the frequency of MDSCs in peripheral blood, and immunohistochemistry was performed to determine the distribution of MDSCs in primary NEN tissues.

Results: Compared to healthy donors, patients with GEP-NENs had significantly higher levels of circulating monocytic (M)-MDSCs. Frequency of M-MDSCs in both peripheral blood and primary NEN tissues was significantly higher in GEP-NEN patients with metastases compared to patients without metastases. Tumor-infiltrating M-MDSCs can serve as a valuable prognostic marker of metastasis in patients with GEP-NENs, as indicated by the area under the curve (AUC) = 0.71; 95% confidence interval (CI) = 0.56-0.87, p < 0.01.

Conclusions: High M-MDSC levels were associated with significantly increased metastases in patients with GEP-NENs. M-MDSCs appear to be a promising prognostic immunologic biomarker and therapeutic target in GEP-NEN management.
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http://dx.doi.org/10.1007/s12020-020-02467-2DOI Listing
January 2021

Epstein-Barr virus infection in ulcerative colitis: a clinicopathologic study from a Chinese area.

Therap Adv Gastroenterol 2020 18;13:1756284820930124. Epub 2020 Aug 18.

Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, NO.58 Zhongshan Road II, Guangzhou 510080, Guangdong Province, P.R. China.

Background: Opportunistic Epstein-Barr virus (EBV) infection in patients with ulcerative colitis (UC) has attracted increasing attention. This study aimed to evaluate the clinicopathological characteristics and clinical outcomes of UC with intestinal EBV infection and to explore the predictive value of blood EBV DNA for the presence of EBV in the intestine.

Methods: Both peripheral blood and intestinal biopsies from 92 consecutive UC inpatients were included in this study. Normal colonic mucosal tissues from 20 colon cancer patients were used as controls. EBV testing and assessment were performed by EBV-DNA polymerase chain reaction (PCR), EBV-encoded small RNA hybridization (EBER-ISH) and immunohistochemistry.

Results: A total of 36 patients (39.1%) had UC with superimposed EBV colitis [EBER greater than 2/high-power field (HPF)]. EBER counts and disease activity were significantly correlated ( < 0.05). The major endoscopic findings revealed more irregular and longitudinal ulcers in patients with superimposed EBV colitis ( = 0.016,  = 0.021, respectively). Age, steroid dependence, and irregular ulcerations were identified as possible risk factors. The best EBER cut-off point for outcome prediction was 2.5/HPF. At a cut-off value of 2035 copies/ml, the sensitivity and specificity of the blood EBV-DNA PCR analysis for predicting EBV presence in the intestine were 76.5% and 68.5%, respectively. EBV-infected cells in UC with high EBV concentrations mainly included B lymphocytes by clinicopathology, and the infection might have progressed from the latent to the lytic phase of the EBV life cycle.

Conclusion: The EBER count is positively correlated with disease activity. The best cut-off point for outcome prediction is 2.5/HPF. A high EBV viremia load may effectively predict EBV presence in the colonic mucosa.
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http://dx.doi.org/10.1177/1756284820930124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444145PMC
August 2020

Nomogram for individually predicting overall survival in rectal neuroendocrine tumours.

BMC Cancer 2020 Sep 9;20(1):865. Epub 2020 Sep 9.

Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, The Second School of Clinical Medicine, Southern Medical University, No. 106, Zhongshan Er Road, Guangzhou, P.R. China.

Background: This study aimed to develop a nomogram that predicts the overall survival (OS) of rectal neuroendocrine tumours (NETs).

Methods: We retrospectively analysed 310 patients with rectal neuroendocrine tumours in 5 hospitals in southern China. All of the patients were assigned to the training set. A multivariable analysis using Cox proportional hazards regression was performed using the training set, and a nomogram was constructed. It was validated on a dataset obtained from the Surveillance, Epidemiology, and End Result (SEER) database of America (n = 547).

Results: In the training set, the nomogram exhibited improved discrimination power compared with the WHO grade guidelines (Herrell's C-index, 0.872 vs 0.794; p < 0.001) and was also better than the seventh AJCC TNM classification (Herrell's C-index, 0.872 vs 0.817; p < 0.001). In the SEER validation dataset, the discrimination was also excellent (C-index, 0.648 vs 0.583, p < 0.001 and 0.648 vs 0.603, p = 0.016, respectively, compared with G grade and TNM classification). Calibration of the nomogram predicted individual survival corresponding closely with the actual survival.

Conclusions: We developed a nomogram predicting 1- and 3-year OS of patients with rectal neuroendocrine tumours. Validation revealed excellent discrimination and calibration, suggesting good clinical utility.
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http://dx.doi.org/10.1186/s12885-020-07328-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488006PMC
September 2020

Systematic review with meta-analysis of partial enteral nutrition for the maintenance of remission in Crohn's disease.

Nutr Res 2020 09 9;81:7-18. Epub 2020 Jun 9.

Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan Road II, Yuexiu district, Guangzhou 510000, P.R. China. Electronic address:

Although enteral nutrition (EN) is effective for induction therapy in Crohn's disease (CD), it remains unclear whether partial enteral nutrition (PEN), i.e., EN, along with a daily diet, is effective for maintenance therapy in CD. It was hypothesized that PEN would be effective as a maintenance therapy in CD. This meta-analysis aimed to evaluate the efficacy and safety of PEN for maintenance therapy in CD. PubMed, EMBASE, Web of Science, and Cochrane Library were searched up to January 2019 for eligible prospective controlled trials, and then a meta-analysis was conducted. The primary outcome was clinical relapse, as defined in the primary studies. Eight studies with 429 patients were included in the meta-analysis. The rate of clinical relapse at 0.5 to 2 years was significantly lower in patients receiving PEN (420-1800 kcal/d) than in those not receiving nutrition therapy (RR: 0.67, 95% CI: 0.54-0.82, P < .01; number needed to treat = 5, P < .01). Patients receiving PEN exhibited a higher frequency of clinical remission maintenance at 0.5 to 1 year (67%) than did those not receiving nutrition therapy (48%; RR: 1.32, 95% CI: 1.07-1.64, P = .01). The total adverse event rate was comparable in the two groups (RR: 3.60, 95% CI: 0.70-18.66, P = .13). PEN may be more effective than the absence of EN therapy for the maintenance of remission in CD with a good safety profile.
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http://dx.doi.org/10.1016/j.nutres.2020.06.006DOI Listing
September 2020

A20 Haploinsufficiency in a Chinese Patient With Intestinal Behcet's Disease-Like Symptoms: A Case Report.

Front Immunol 2020 3;11:1414. Epub 2020 Jul 3.

Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Intestinal Behcet's disease (iBD) is an autoimmune disorder diagnosed by typical intestinal ulcers and systemic Behcet's disease (BD) manifestations. Haploinsufficiency of A20 (HA20) is a recently described autoinflammatory disease with a phenotype resembling BD, caused by heterozygous loss-of-function mutations in gene (encoding A20). We described a 29-year-old female with iBD-like symptoms including relapsing ulceration of intestinal anastomosis, recurrent oral ulcers and vasculitis in extremities. Due to the atypical intestinal ulcers with long segmental involvement and intestinal obstruction, whole exome sequencing (WES) was performed to screen for the underlying genetic defect and the identified gene was confirmed by Sanger sequencing. The expression levels of A20 was evaluated by Western blot. Sanger sequencing and Western blot were also performed in the patient's family members. A heterozygous mutation of (c.305A>G, p. Asn 102 Ser) was identified in the patient. The identical mutation was also found in her father and brother who had suffered from recurrent oral ulcers since childhood. Functional experiments revealed that the expression of A20 was decreased in the peripheral blood mononuclear cells of the patient and her family members who carried the TNFAIP3 mutation. We described a Chinese patient with a novel heterozygous mutation in who developed iBD-like symptoms. We proposed that the heterozygous mutation (c.305A>G, p. Asn 102 Ser) with an insufficient expression of A20 may be associated with the iBD phenotype in patients.
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http://dx.doi.org/10.3389/fimmu.2020.01414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348591PMC
April 2021

Asian Organization for Crohn's and Colitis and Asia Pacific Association of Gastroenterology practice recommendations for medical management and monitoring of inflammatory bowel disease in Asia.

J Gastroenterol Hepatol 2021 Mar 29;36(3):637-645. Epub 2020 Jul 29.

Department of Gastroenterology, Peking Union Medical College, Beijing, China.

Inflammatory bowel disease (IBD) has increased in incidence and prevalence in Asian countries since the end of the 20th century. Moreover, differences in the cause, phenotypes, and natural history of IBD between the East and West have been recognized. Therefore, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have established recommendations on medical management of IBD in Asia. Initially, the committee members drafted 40 recommendations, which were then assessed according to Grading of Recommendations Assessment, Development and Evaluation. Eight statements were rejected as this indicated that consensus had not been reached. The recommendations encompass pretreatment evaluation; medical management of active IBD; medical management of IBD in remission; management of IBD during the periconception period and pregnancy; surveillance strategies for colitis-associated cancer; monitoring side effects of thiopurines and methotrexate; and infections in IBD.
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http://dx.doi.org/10.1111/jgh.15185DOI Listing
March 2021

High-Throughput Screen Identifies Host and Microbiota Regulators of Intestinal Barrier Function.

Gastroenterology 2020 11 9;159(5):1807-1823. Epub 2020 Jul 9.

Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel; Immunology Department, Weizmann Institute of Science, Rehovot, Israel. Electronic address:

Background & Aims: The intestinal barrier protects intestinal cells from microbes and antigens in the lumen-breaches can alter the composition of the intestinal microbiota, the enteric immune system, and metabolism. We performed a screen to identify molecules that disrupt and support the intestinal epithelial barrier and tested their effects in mice.

Methods: We performed an imaging-based, quantitative, high-throughput screen (using CaCo-2 and T84 cells incubated with lipopolysaccharide; tumor necrosis factor; histamine; receptor antagonists; and libraries of secreted proteins, microbial metabolites, and drugs) to identify molecules that altered epithelial tight junction (TJ) and focal adhesion morphology. We then tested the effects of TJ stabilizers on these changes. Molecules we found to disrupt or stabilize TJs were administered mice with dextran sodium sulfate-induced colitis or Citrobacter rodentium-induced intestinal inflammation. Colon tissues were collected and analyzed by histology, fluorescence microscopy, and RNA sequencing.

Results: The screen identified numerous compounds that disrupted or stabilized (after disruption) TJs and monolayers of epithelial cells. We associated distinct morphologic alterations with changes in barrier function, and identified a variety of cytokines, metabolites, and drugs (including inhibitors of actomyosin contractility) that prevent disruption of TJs and restore TJ integrity. One of these disruptors (putrescine) disrupted TJ integrity in ex vivo mouse colon tissues; administration to mice exacerbated colon inflammation, increased gut permeability, reduced colon transepithelial electrical resistance, increased pattern recognition receptor ligands in mesenteric lymph nodes, and decreased colon length and survival times. Putrescine also increased intestine levels and fecal shedding of viable C rodentium, increased bacterial attachment to the colonic epithelium, and increased levels of inflammatory cytokines in colon tissues. Colonic epithelial cells from mice given putrescine increased expression of genes that regulate metal binding, oxidative stress, and cytoskeletal organization and contractility. Co-administration of taurine with putrescine blocked disruption of TJs and the exacerbated inflammation.

Conclusions: We identified molecules that disrupt and stabilize intestinal epithelial TJs and barrier function and affect development of colon inflammation in mice. These agents might be developed for treatment of barrier intestinal impairment-associated and inflammatory disorders in patients, or avoided to prevent inflammation.
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http://dx.doi.org/10.1053/j.gastro.2020.07.003DOI Listing
November 2020

Which long noncoding RNAs and circular RNAs contribute to inflammatory bowel disease?

Cell Death Dis 2020 06 15;11(6):456. Epub 2020 Jun 15.

Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China.

Inflammatory bowel disease (IBD), a chronic relapsing gastrointestinal inflammatory disease, mainly comprises ulcerative colitis (UC) and Crohn's disease (CD). Although the mechanisms and pathways of IBD have been widely examined in recent decades, its exact pathogenesis remains unclear. Studies have focused on the discovery of new therapeutic targets and application of precision medicine. Recently, a strong connection between IBD and noncoding RNAs (ncRNAs) has been reported. ncRNAs include microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs). The contributions of lncRNAs and circRNAs in IBD are less well-studied compared with those of miRNAs. However, lncRNAs and circRNAs are likely to drive personalized therapy for IBD. They will enable accurate diagnosis, prognosis, and prediction of therapeutic responses and promote IBD therapy. Herein, we briefly describe the molecular functions of lncRNAs and circRNAs and provide an overview of the current knowledge of the altered expression profiles of lncRNAs and circRNAs in patients with IBD. Further, we discuss how these RNAs are involved in the nosogenesis of IBD and are emerging as biomarkers.
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http://dx.doi.org/10.1038/s41419-020-2657-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295799PMC
June 2020

Peroral endoscopic myotomy for patients with achalasia with previous Heller myotomy: a systematic review and meta-analysis.

Gastrointest Endosc 2021 01 11;93(1):47-56.e5. Epub 2020 Jun 11.

Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Background And Aims: Heller myotomy (HM) is considered the standard surgical treatment for patients with achalasia. However, approximately 10% to 20% of patients with achalasia have persistent or recurrent symptoms after HM that require further therapy. Several studies have reported the outcomes of peroral endoscopic myotomy (POEM) in these patients. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of POEM in patients with achalasia with previous HM.

Methods: An electronic literature search of PubMed, Embase, and the Cochrane Library was conducted up to January 31, 2020. Studies evaluating the outcomes of POEM in patients with achalasia with previous HM were eligible for inclusion. The primary outcomes were the pooled rates of clinical success (defined as post-POEM Eckardt score ≤3), mean change in Eckardt score, lower esophageal sphincter pressure, and integrated relaxation pressure (IRP). The secondary outcomes were procedure-related adverse events (AEs) and incidence of postoperative GERD.

Results: A total of 9 studies involving 272 patients with achalasia were recruited in this review. POEM was successfully performed in 270 (99.3%) patients after previous HM. Clinical success was achieved in 90.0% (95% confidence interval [CI], 83.1%-96.8%) of patients. Eckardt score, lower esophageal sphincter pressure, and IRP were significantly lowered by 5.14 (95% CI, 4.19-6.09), 12.01 mm Hg (95% CI, 6.74-17.27), and 10.02 mm Hg (95% CI, 4.95-15.09), respectively. The pooled rates of postoperative symptomatic reflux, esophagitis, and abnormal pH monitoring were 36.9% (95% CI, 20.7%-53.1%), 33.0% (95% CI, 9.6%-56.4%), and 47.8% (95% CI, 33.4%-62.2%), respectively. Substantial heterogeneity was detected across all outcome measurements. Most of the AEs were self-limiting or managed conservatively.

Conclusions: POEM is a safe and effective treatment for patients with achalasia with previous HM. Further data from prospective, controlled studies with long-term follow-up are needed to confirm these findings.
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http://dx.doi.org/10.1016/j.gie.2020.05.056DOI Listing
January 2021

"It ain't over … till it's over!" Risk-mitigation strategies for patients with gastrointestinal diseases in the aftermath of the COVID-19 pandemic.

J Gastroenterol Hepatol 2020 Jul 29;35(7):1117-1123. Epub 2020 Jun 29.

Clínica de Gastroenterología, Faculta de Medicina, Montevideo, Uruguay.

The available COVID-19 literature has focused on specific disease manifestations, infection control, and delivery or prioritization of services for specific patient groups in the setting of the acute COVID-19 pandemic. Local health systems aim to contain the COVID-19 pandemic and hospitals and health-care providers rush to provide the capacity for a surge of COVID-19 patients. However, the short, medium-term, and long-term outcomes of patients with gastrointestinal (GI) diseases without COVID-19 will be affected by the ability to develop locally adapted strategies to meet their service needs in the COVID-19 setting. To mitigate risks for patients with GI diseases, it is useful to differentiate three phases: (i) the acute phase, (ii) the adaptation phase, and (iii) the consolidation phase. During the acute phase, service delivery for patients with GI disease will be curtailed to meet competing health-care needs of COVID-19 patients. During the adaptation phase, GI services are calibrated towards a "new normal," and the consolidation phase is characterized by rapid introduction and ongoing refinement of services. Proactive planning with engagement of relevant stakeholders including consumer representatives is required to be prepared for a variety of scenarios that are dictated by thus far undefined long-term economic and societal impacts of the pandemic. Because substantial changes to the delivery of services are likely to occur, it is important that these changes are embedded into quality and research frameworks to ensure that data are generated that support evidence-based decision-making during the adaptation and consolidation phases.
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http://dx.doi.org/10.1111/jgh.15133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300751PMC
July 2020

Normalization of C-Reactive Protein Predicts Better Outcome in Patients With Crohn's Disease With Mucosal Healing and Deep Remission.

Clin Transl Gastroenterol 2020 02;11(2):e00135

Department of Gastroenterology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

Objectives: Therapeutic targets for Crohn's disease (CD) have evolved from clinical and biological remission to mucosal healing (MH) and deep remission (DR). MH is defined as disappearance of ulceration, whereas DR is defined as a combination of clinical remission and MH. Limited data are available regarding differences in long-term outcomes of these patients reaching these targets. We thus aimed to evaluate patients' long-term clinical outcomes using different composite remission parameters.

Methods: We performed a retrospective cohort study comparing long-term outcomes of patients with different remission parameters, including MH and DR with or without normalization of C-reactive protein (CRPnorm). The primary outcome was CD-associated intestinal surgery, and secondary outcomes included CD-related hospitalizations, clinical relapse (CR), or endoscopic recurrence (ER).

Results: One hundred ninety-five patients with MH at follow-up endoscopy were divided into 3 groups: DR-only (n = 53), DR + CRPnorm (n = 106), and MH-only (n = 36). At the follow-up (median 46.0 months), 25 patients had undergone CD-related bowel surgery, 44 had CD-related hospitalizations, and 66 experienced CR. Of 151 patients who underwent follow-up colonoscopy after the index colonoscopy for MH, 96 experienced ER. Among the 3 groups, patients in the DR + CRPnorm group had the lowest risk of clinical or endoscopic relapse. The DR group had a lower rate of CR than the MH-only group (P = 0.03); there was no difference in the rate of CD-related surgery, hospitalizations, or ER.

Discussion: Patients with DR combined with a normalized CRP showed better outcomes than those with DR only. The outcomes of patients with MH were similar to those of patients with DR, except for shorter flare-free survival.
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http://dx.doi.org/10.14309/ctg.0000000000000135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145028PMC
February 2020

Serum Biomarkers for Inflammatory Bowel Disease.

Front Med (Lausanne) 2020 22;7:123. Epub 2020 Apr 22.

Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a chronic, inflammatory disorder of the gastrointestinal tract. As the novel therapeutic goal and biologicals are widely recognized, accurate assessment of disease and prediction of therapeutic response have become a crucial challenge in clinical practice. Also, because of the continuously rising incidence, convenient and economical methods of diagnosis and clinical assessment are urgently needed. Recently, serum biomarkers have made a great progress and become a focus in IBD study because they are non-invasive, convenient, and relatively inexpensive than are markers in biopsy tissue, stool, breath, and other body fluids. To review the available data on serological biomarkers for IBD. We searched PubMed using predefined key words on relevant literatures of serum biomarkers regarding diagnosis, evaluation of therapeutic efficacy, surveillance of disease activity, and assessment of prognosis for IBD. We reviewed serological biomarkers that are well-established and widely used (e.g., C-reactive protein), newly discovered biomarkers (e.g., cytokines, antibodies, and non-coding RNAs), and also recently advancements in serological biomarkers (e.g., metabolomics and proteomics) that are used in different aspects of IBD management. With such a wealth of researches, to date, there are still no ideal serum biomarkers for IBD. Serum profiling and non-coding RNAs are just starting to blossom but reveal great promise for future clinical practice. Combining different biomarkers can be valuable in improving performance of disease evaluation.
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http://dx.doi.org/10.3389/fmed.2020.00123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188783PMC
April 2020
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