Bile acid signaling through farnesoid X and TGR5 receptors in hepatobiliary and intestinal diseases

BACKGROUND： The well-known functions of bile acids（BAs） are the emulsification and absorption of lipophilic xenobiotics. However, the emerging evidences in the past decade showed that BAs act as signaling molecules that not only autoregulate their own metabolism and enterohepatic recirculation, but also as important regulators of integrative metabolism by activating nuclear and membrane-bound G protein-coupled receptors. The present review was to get insight into the role of maintenance of BA homeostasis and BA signaling pathways in development and management of hepatobiliary and intestinal diseases.DATA SOURCES： Detailed and comprehensive search of PubM ed and Scopus databases was carried out for original and review articles.RESULTS： Disturbances in BA homeostasis contribute to the development of several hepatobiliary and intestinal disorders, such as non-alcoholic fatty liver disease, liver cirrhosis, cholesterol gallstone disease, intestinal diseases and both hepatocellular and colorectal carcinoma.CONCLUSION： Further efforts made in order to advance the understanding of sophisticated BA signaling network may be promising in developing novel therapeutic strategies related not only to hepatobiliary and gastrointestinal but also systemic diseases.

Capsule endoscopy in non-steroidal anti-inflammatory drugs-enteropathy and miscellaneous,rare intestinal diseases

Despite significant advances over the last decade, mucosal lesions of the small bowel are poorly detected by imaging studies such as CT scan, MRI-enteroclysis and contrast-enhanced abdominal ultrasound. Capsule endoscopy (CE) has dramatically changed the diagnostic approach to intestinal diseases. Moreover, the use of CE can be extended to include other conditions. However, it is diffi cult to assess the positive influence of CE on patient outcomes in conditions involving a small number of patients, or in critically ill and diff icult to examine patients. CE has the advantage of diagnosing intestinal lesions and of directing the use of double balloon enteroscopy (DBE) in order to obtain biopsy specimens. Moreover, CE allows repeated assessment in chronic conditions, especially to detect relapse of an infectious disease.

Intestinal disease of scattered mirror carp Cyprinus carpio caused by Thelohanellus kitauei and notes on the morphology and phylogeny of the myxosporean from Sichuan Province,southwest China

The mass mortality of pond-reared scattered mirror carp, Cyprinus carpio, caused by Thelohanellus kitauei, occurred at fish farms in Sichuan Province, southwest China. Morphological and molecular analyses were supplemented with histological evaluation of infected tissues to better understand the route of infection and the pathological effects of 1＂. kitauei on the fish host. The intestine of the diseased host was full of large cysts of the myxosporean. The cysts range from 2 cm to 3.6 cm in diameter. Histopathology indicated that T. kitauei first invaded the submucosa of the host intestine and then moved into the mucosa layers with the development of their spores, finally entering into the enteric cavity of the hosts after the disruption of mucosa layers. The pyriform spores of T. kitauei were surrounded by the transparent spore sheath, measuring 25.98/μm±0.95 μm in body length, 8.72 μm±0.51μm body width, and 7.86 μm±0.26 μm in body thickness. The single polar capsule was pyriform, measuring 14.73 μm±0.92μm in length and 6.82 μm±0.45μm in width, with eight to 10 turns of filament coils winding inside. Phylogenetic analysis based on the 18S small-subunit ribosomal DNA sequences indicated that minimal genetic differences were present between T. kitauei samples from South Korea and from China. Close affinity was found between the genus Thelohanellus and Myxobolus. Additionally, two polar capsule nuclei were found at the anterior end of the single polar capsule in spores of T. kitauei stained with hematoxylin and eosin, which suggested the separation of the genus Thelohanellus from Myxobolus.

Artificial intelligence in small intestinal diseases:Application and prospects

The small intestine is located in the middle of the gastrointestinal tract,so small intestinal diseases are more difficult to diagnose than other gastrointestinal diseases.However,with the extensive application of artificial intelligence in the field of small intestinal diseases,with its efficient learning capacities and computational power,artificial intelligence plays an important role in the auxiliary diagnosis and prognosis prediction based on the capsule endoscopy and other examination methods,which improves the accuracy of diagnosis and prediction and reduces the workload of doctors.In this review,a comprehensive retrieval was performed on articles published up to October 2020 from PubMed and other databases.Thereby the application status of artificial intelligence in small intestinal diseases was systematically introduced,and the challenges and prospects in this field were also analyzed.

Helminths as an alternative therapy for intestinal diseases

Animal models and clinical studies have shown that helminth infections exert immunomodulatory activity,altering intestinal permeability and providing a potential beneficial action on autoimmune and inflammatory disorders in human beings,such as inflammatory bowel disease(IBD) and celiac disease. This is consistent with the theory that intestinal microbiota is responsible for shaping human immunological responses. With the arrival of the immunobiologic era and the use of antibodies,we propose a distinctive pathway for treating patients with IBD and celiac disease. We have some evidence about the safety and tolerability of helminth use,but evidence about their impact on disease activity is lacking. Using worms to treat diseases could be a possible way to lower treatment costs,since the era of immunobiologic agents is responsible for a significant rise in expenses. Some questions remain to be investigated regarding the use of helminths in intestinal disease,such as the importance of the specific species of helminths used,appropriate dosing regimens,optimal timing of treatment,the role of host genetics,diet,environment,and the elucidation of the exact mechanisms of action. One promising approach is the use of helminth-derived anti-inflammatory molecules as drugs. Yet there are still many challenges with this method,especially with regard to safety. Studies on intestinal permeability point to Strongyloides stercoralis as a useful nematode for these purposes.

Necroptosis in inflammatory bowel disease and other intestinal diseases

Guo-Qiang XuFor a long time, it was believed that apoptosis and necrosis were the main pathways for cell death, but a growing body of research has shown that there are other pathways. Among these, necroptosis, a regulatory caspase-independent, programmed cell death pathway, is supposed to be of importance in the pathogenesis of many diseases. The mechanism of regulating, in-ducing and blocking necroptosis is a complex process that involves expression and regulation of a series of molecules including receptor interacting protein kinase 1 （RIPK1）, RIPK3, and mixed lineage kinase like protein. By blocking or downregulating expression of key molecules in the necroptotic pathway, intestinal inflammation can be affected to some extent. In this paper, we introduce the concept of necroptosis, its main pathway, and its impact on the pathogenesis ofinfammatory bowel disease （IBD） and other intestinal diseases, to explore new drug targets for intestinal diseases, including IBD.

Intestinal Behçet's disease: A review of clinical diagnosis and treatment

Behçet's disease(BD)is a chronic inflammatory disorder prone to frequent re-currences,with a high predilection for intestinal involvement.However,the ef-ficacy and long-term effects of surgical treatment for intestinal BD are unknown.In the current issue of World J Gastrointest Surg,Park et al conducted a retrospec-tive analysis of 31 patients with intestinal BD who received surgical treatment.They found that elevated C-reactive protein levels and emergency surgery were poor prognostic factors for postoperative recurrence,emphasizing the adverse impact of severe inflammation on the prognosis of patients with intestinal BD.This work has clinical significance for evaluating the postoperative condition of intestinal BD.The editorial attempts to summarize the clinical diagnosis and treatment of intestinal BD,focusing on the impact of adverse factors on surgical outcomes.We hope this review will facilitate more precise postoperative management of patients with intestinal BD by clinicians.

Unresolved conundrum of the role of physical activity in inflammatory bowel disease:What next?

There is considerable controversy on the role of physical activity in irritable bowel disease(IBD)since published reports are conflicting.It is well known that there is known relapse with specific treatment in IBD.This,in addition to onset of extraintestinal symptoms creates a need to think of alternate approaches.In this context,the current article describes the need of a multi-institutional study with standard protocol of physical activity for documenting its effect on both the primary disease and the extra alimentary manifestations.This paper also points out the possibility of using adjuvant complementary medicine such as yoga,whose effects have been documented in other diseases like irritable bowel syndrome.A third approach could be to focus on the intestinal dysbiosis in IBD and concentrate on research on restoring the microbial flora to normal,to see whether the extraintestinal symptoms are alleviated.

Autophagy and tight junction proteins in the intestine and intestinal diseases

The intestinal epithelium(IE) forms an indispensible barrier and interface between the intestinal interstitium and the luminal environment. The IE regulates water, ion and nutrient transport while providing a barrier against toxins, pathogens(bacteria, fungi and virus) and antigens. The apical intercellular tight junctions(TJ) are responsible for the paracellular barrier function and regulate transepithelial flux of ions and solutes between adjacent cells. Increased intestinal permeability caused by defects in the IE TJ barrier is considered an important pathogenic factor for the development of intestinal inflammation, diarrhea and malnutrition in humans and animals. In fact, defects in the IE TJ barrier allow increased antigenic penetration, resulting in an amplified inflammatory response in inflammatory bowel disease(IBD), necrotizing enterocolitis and ischemia-reperfusion injury. Conversely, the beneficial enhancement of the intestinal TJ barrier has been shown to resolve intestinal inflammation and apoptosis in both animal models of IBD and human IBD. Autophagy(self-eating mechanism) is an intracellular lysosome-dependent degradation and recycling pathway essential for cell survival and homeostasis.Dysregulated autophagy has been shown to be directly associated with many pathological processes,including IBD. Importantly, the crosstalk between IE TJ and autophagy has been revealed recently. We showed that autophagy enhanced IE TJ barrier function by increasing transepithelial resistance and reducing the paracellular permeability of small solutes and ions, which is, in part, by targeting claudin-2,a cation-selective, pore-forming, transmembrane TJ protein, for lysosome(autophagy)-mediated degradation. Interestingly, previous studies have shown that the inflamed intestinal mucosa in patients with active IBD has increased claudin-2 expression. In addition, inflammatory cytokines(for example,tumor necrosis factor-α, interleukin-6, interleukin-13, and interleukin-17) whose levels are increased in IBD patients cause an increase in claudin-2 expression and a claudin-2-dependent increase in TJ permeability. Thus, the role of claudin-2 in intestinal pathological processes has been attributed, in part, to the increase of intestinal TJ permeability. Claudin-2 represents a new therapeutic target in treating IBD,diarrhea and malnutrition in animals and humans.

Role of Toll-like receptors in health and diseases of gastrointestinal tract

The human gastrointestinal （GI） tract is colonized by non-pathogenic commensal microflora and frequently exposed to many pathogenic organisms. For the maintenance of GI homeostasis, the host must discriminate between pathogenic and non-pathogenic organisms and initiate effective and appropriate immune and inflammatory responses. Mammalian tolllike receptors （TLRs） are members of the patternrecognition receptor （PRR） family that plays a central role in the initiation of innate cellular immune responses and the subsequent adaptive immune responses to microbial pathogens. Recent studies have shown that gastrointestinal epithelial cells express almost all TLR subtypes characterized to date and that the expression and activation of TLRs in the GI tract are tightly and coordinately regulated. This review summarizes the current understanding of the crucial dual roles of TLRs in the development of host innate and adaptive immune responses to GI infections and the maintenance of the immune tolerance to commensal bacteria through downregulation of surface expression of TLRs in intestinal epithelial cells.

Literature-based analysis on relationship of symptoms,drugs and therapies in treatment of intestinal diseases

OBJECTIVE:To evaluate clinical articles published in the past 30 years using the Traditional Chinese Medicine(TCM)theory of the lung being connected with large intestine to treat intestinal diseases.We also analyzed the relationship between symptoms,drugs and therapies with data-excavating technology to aid management.METHODS:After retrieving relevant clinical articles,we set up a database,used Microsoft Structured Query Language Server 2005 Analysis Services as a data-excavating tool,and applied the association rule to study the relationship between the symptoms,drugs and therapies of intestinal diseases.RESULTS:The key symptoms of dyschesia,constipation,abdominal fullness,fatigue and pale tongue could be treated with Kuxingren(Semen Armeniacae Amarum),Huangqi(Radix Astragali Mongolici)and Gualou(Fructus et Semen Trichosanthis)to invigorate Qi and moisten the intestine.Among these agents,Kuxingren(Semen Armeniacae Amarum)was used most frequently.Clearing Fu-organs was the most prevalent therapy for abdominal fullness,dyschesia,constipation and red tongue.Clearing Fu-organs could be achieved with Kuxingren(Semen Armeniacae Amarum)and Gualou(Fructus et Semen Trichosanthis),whereas Qi could be invigorated using Huangqi(Radix Astragali Mongolici),Gancao(Radix Glycyrrhizae),Baizhu(Rhizoma Atractylodis Macrocephalae)and Kuxingren(Semen Armeniacae Amarum).Moistening the intestine was possible with Kuxingren(SemenArmeniacae Amarum),Huomaren(Fructus Cannabis)and Jiegeng(Radix Platycodi).Also,moistening the lungs was done with Kuxingren(Semen Armeniacae Amarum),ventilating the lungs with Kuxingren(Semen Armeniacae Amarum)and Gualou(Fructus et Semen Trichosanthis),and nourishing the lungs with Huangqi(Radix Astragali Mongolici),Gancao(Radix Glycyrrhizae)and Kuxingren(Semen Armeniacae Amarum).These data demonstrated that Kuxingren(SemenArmeniacaeAmarum)was a key agent.CONCLUSION:Our analyses of the literature showed clear relationships between symptoms(constipation,dyschesia,abdominal fullness),drugs[Gualou(Fructus et Semen Trichosanthis),Kuxingren(Semen Armeniacae Amarum),Huangqi(Radix Astragali Mongolici)]and therapies(moistening the intestine,clearing Fu-organs,invigorating Qi,ventilating the lungs).

Application of double-balloon enteroscopy in the diagnosis and therapy of small intestinal diseases

Background X-ray of the digestive tract and radionuclide examination could not accurately detect diseases of the small intestine. Double-balloon enteroscopy has been used to increase the detection rate of these diseases in addition to endoscopic biopsy and therapy. The purpose of this study was to determine the value of double-balloon enteroscopy in the diagnosis and treatment of diseases of the small intestine. Methods A total of 258 double-balloon enteroscopies via the mouth and/or anus were performed in 208 patients. If no lesion was detected on one side （mouth or anus）, examination on the other side （anus or mouth） was made. If active small intestinal bleeding was detected, endoscopic hemostasis was done to treat the bleeding. Results In the 208 patients, 50 were subjected to double-balloon enteroscopy via both mouth and anus. Lesions were detected in 151 patients, giving a rate of 72.6% （151/208）. The detection rates for obscure digestive tract bleeding, diarrhea, abdominal pain and weight loss were 90.2% （92/102）, 64.9% （24/37）, 48.5% （16/33） and 43.3% （13/30）, respectively. Lesions of the 151 patients were confirmed by endoscopic biopsy, surgery, clinical studies, and follow-up. In the 102 patients with bleeding of the digestive tract, active bleeding was detected in 27 patients. Endoscopic hemostasis was successful in 25 of them （92.6%, 25/27）. No serious complications occurred in all the patients, the average time for the procedure was 100 minutes. Conclusions Double-balloon enteroscopy is safe, effective in the diagnosis of diseases of the small intestine in addition to endoscopic therapy.

Impact of cytomegalovirus intestinal disease on the prognosis in patients with severe intestinal graft-versus-host disease

Objective To explore risk factors,clinical characteristics and prognosis of CMV enteritis combined with severe intestinal graft-versus-host disease(GVHD).Methods The data of 80 intestinal gradeⅢ/ⅣGVHD patients from January 2005 to September 2015 in hematology of PKUPH were retrospectively analyzed.All patients received colonoscopy and all GVHD diagnoses

Intestinal Behcet's disease with esophageal ulcers and colonic longitudinal ulcers

Intestinal Behcet＇s disease in a 38-year-old woman was diagnosed because of the history of recurrent oral aphthous ulcers, erythema nodosum-like eruptions, genital ulcer, and endoscopic findings of esophageal and Ueocolonic punched-out ulcers with colonic longitudinal ulcers. Esophageal lesions and colonic longitudinal ulcers are rarely seen in intestinal Behcet＇s disease. The ulcers of esophagus and ileocolon healed with 3 wk of treatment with prednisolone and mesalazine without any adverse effect. Mesalazine may decrease the total dose of prednisolone required to treat the disease.

Correlations between endoscopic and clinical disease activity indices in intestinal Behcet's disease

AIM:To develop a novel endoscopic severity model of intestinal Behcet's disease(BD) and to evaluate its feasibility by comparing it with the actual disease activity index for intestinal Behcet's disease(DAIBD).METHODS:We reviewed the medical records of 167 intestinal BD patients between March 1986 and April 2011.We also investigated the endoscopic parameters including ulcer locations,distribution,number,depth,shape,size and margin to identify independent factors associated with DAIBD.An endoscopic severity model was developed using significant colonoscopic variables identified by multivariate regression analysis and its correlation with the DAIBD was evaluated.To determine factors related to the discrepancy between endoscopic severity and clinical activity,clinical characteristics and laboratory markers of the patients were analyzed.RESULTS:A multivariate regression analysis revealed that the number of intestinal ulcers(≥ 2,P = 0.031) and volcanoshaped ulcers(P = 0.001) were predictive factors for the DAIBD.An endoscopic severity model(Y) was developed based on selected endoscopic variables as follows:Y = 47.44 + 9.04 × non-Ileocecal area + 11.85 ×≥ 2 of intestinal ulcers + 5.03 × shallow ulcers + 12.76 × deep ulcers + 4.47 × geographicshaped ulcers + 26.93 × volcano-shaped ulcers + 8.65 ×≥ 20 mm of intestinal ulcers.However,endoscopic parameters used in the multivariate analysis explained only 18.9% of the DAIBD variance.Patients with severe DAIBD scores but with moderately predicted disease activity by the endoscopic severity model had more symptoms of irritable bowel syndrome(21.4% vs 4.9%,P = 0.026) and a lower rate of corticosteroid use(50.0% vs 75.6%,P = 0.016) than those with severe DAIBD scores and accurately predicted disease by the model.CONCLUSION:Our study showed that the number of intestinal ulcers and volcano-shaped ulcers were predictive factors for severe DAIBD scores.However,the correlation between endoscopic severity and DAIBD(r = 0.434) was weak.

Chronic intestinal failure and short bowel syndrome in Crohn’s disease

Chronic intestinal failure(CIF)is a rare but feared complication of Crohn’s disease.Depending on the remaining length of the small intestine,the affected intestinal segment,and the residual bowel function,CIF can result in a wide spectrum of symptoms,from single micronutrient malabsorption to complete intestinal failure.Management of CIF has improved significantly in recent years.Advances in home-based parenteral nutrition,in particular,have translated into increased survival and improved quality of life.Nevertheless,60%of patients are permanently reliant on parenteral nutrition.Encouraging results with new drugs such as teduglutide have added a new dimension to CIF therapy.The outcomes of patients with CIF could be greatly improved by more effective prevention,understanding,and treatment.In complex cases,the care of patients with CIF requires a multidisciplinary approach involving not only physicians but also dietitians and nurses to provide optimal intestinal rehabilitation,nutritional support,and an improved quality of life.Here,we summarize current literature on CIF and short bowel syndrome,encompassing epidemiology,pathophysiology,and advances in surgical and medical management,and elucidate advances in the understanding and therapy of CIF-related complications such as catheter-related bloodstream infections and intestinal failure-associated liver disease.

Intestinal Behet's disease appearing during treatment with adalimumab in a patient with ankylosing spondylitis

Behet’s disease(BD)is a chronic inflammatory disease affecting multiple organ systems,such as the skin,joints,blood vessels,central nervous system,and gastrointestinal tract.Intestinal BD is characterized by intestinal ulcerations and gastrointestinal symptoms.The medical treatment of intestinal BD includes corticosteroids and immunosupressants.There have been several reports of tumor necrosis factor-α (TNF-α)blockers being successful in treatment of refractory intestinal BD.Here,we report on a patient who was diagnosed with intestinal BD despite treatment with the fully humanized TNF-α blocker(adalimumab)for underlying ankylosing spondylitis.This patient achieved clinical remission and complete mucosal healing through the addition of a steroid and azathioprine to the adalimumab regimen.

characteristics of intestinal pseudo-obstruction in patients with mitochondrial diseases

AIM: To reveal the frequency, characteristics and prognosis of chronic intestinal pseudo-obstruction (CIP) in mitochondrial disease patients. METHODS: Between January 2000 and December 2010, 31 patients (13 males and 18 females) were di-agnosed with mitochondrial diseases at our hospital. We conducted a retrospective review of the patients' sex, subclass of mitochondrial disease, age at onset of mitochondrial disease, frequency of CIP and the age at its onset, and the duration of survival. The age at onset or at the first diagnosis of the disorder that led to the clinical suspicion of mitochondrial disease was also examined. RESULTS: Twenty patients were sub-classified with mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS), 8 with chronic progressive external ophthalmoplegia (CPEO), and 3 with myoclonus epilepsy associated with ragged-red fibers (MERRF). Nine patients were diagnosed with CIP, 8 of the 20 (40.0%) patients with MELAS, 0 of the 8 (0.0%) patients with CPEO, and 1 of the 3 (33.3%) patients with MERRF. The median age (range) at the diagnosis and the median age at onset of mitochondrial disease were 40 (17-69) and 25 (12-63) years in patients with CIP, and 49 (17-81) and 40 (11-71) years in patients without CIP. During the survey period, 5 patients (4 patients with MELAS and 1 with CPEO) died. The cause of death was cardiomyopathy in 2 patients with MELAS, cerebral infarction in 1 patient with MELAS, epilepsy and aspiration pneumonia in 1 patient with MELAS, and multiple metastases from gastric cancer and aspiration pneumonia in 1 patient with CPEO. CONCLUSION: Patients with CIP tend to have disorders that are suspected to be related to mitochondrial diseases at younger ages than are patients without CIP.

Intestinal barrier in inflammatory bowel disease

A complex mucosal barrier protects as the first line of defense the surface of the healthy intestinal tract from adhesion and invasion by luminal microorganisms. In this review, we provide an overview about the major components of this protective system as for example an intact epithelium, the synthesis of various antimicrobial peptides (AMPs) and the formation of the mucus layer. We highlight the crucial importance of their correct functioning for the maintenance of a proper intestinal function and the prevention of dysbiosis and disease. Barrier disturbances including a defective production of AMPs, alterations in thickness or composition of the intestinal mucus layer, alterations of pattern-recognition receptors, defects in the process of autophagy as well as unresolved endoplasmic reticulum stress result in an inadequate host protection and are thought to play a crucial role in the pathogenesis of the inflammatory bowel diseases Crohn’s disease and ulcerative colitis.

Bilateral pneumothorax and pneumomediastinum during colonoscopy in a patient with intestinal Behcet’s disease:A case report

BACKGROUND Colonoscopy is essential for the diagnosis of intestinal Behcet’s disease(BD),which is characterized by a typical oval-shaped ulcer in the ileocecal region.However,potential risks of colonoscopy have rarely been reported.CASE SUMMARY Herein,we describe a patient with intestinal BD who presented with decreased oxygen saturation and shortness of breath during a diagnostic colonoscopy.Bilateral pneumothorax,pneumomediastinum,pneumoperitoneum,pneumoretroperitoneum and subcutaneous emphysema of the neck,chest,abdomen,back and scrotum were confirmed by computed tomography scan.The sudden change in condition was considered to be associated with iatrogenic bowel perforation.After receiving closed thoracic drainage and conservative therapy,the patient was discharged in stable condition.CONCLUSION Endoscopists should be aware of the risks of colonoscopy in patients with intestinal BD and the possibility of pneumothorax associated with intestinal perforation and make adequate preparations before colonoscopy.