Crohn’s disease as the intestinal manifestation of pan-lymphatic dysfunction:An exploratory proposal based on basic and clinical data

Crohn’s disease(CD)is caused by immune,environmental,and genetic factors.It can involve the entire gastrointestinal tract,and although its prevalence is rapidly increasing its etiology remains unclear.Emerging biological and small-molecule drugs have advanced the treatment of CD;however,a considerable proportion of patients are non-responsive to all known drugs.To achieve a breakthrough in this field,innovations that could guide the further development of effective therapies are of utmost urgency.In this review,we first propose the innovative concept of pan-lymphatic dysfunction for the general distribution of lymphatic dysfunction in various diseases,and suggest that CD is the intestinal manifestation of pan-lymphatic dysfunction based on basic and clinical preliminary data.The supporting evidence is fully summarized,including the existence of lymphatic system dysfunction,recognition of the inside-out model,disorders of immune cells,changes in cell plasticity,partial overlap of the underlying mechanisms,and common gut-derived fatty and bile acid metabolism.Another benefit of this novel concept is that it proposes adopting the zebrafish model for studying intestinal diseases,especially CD,as this model is good at presenting and mimicking lymphatic dysfunction.More importantly,the ensuing focus on improving lymphatic function may lead to novel and promising therapeutic strategies for CD.

Clinical manifestation,lifestyle,and treatment patterns of chronic erosive gastritis:A multicenter real-world study in China

BACKGROUND Although chronic erosive gastritis(CEG)is common,its clinical characteristics have not been fully elucidated.The lack of consensus regarding its treatment has resulted in varied treatment regimens.AIM To explore the clinical characteristics,treatment patterns,and short-term outcomes in CEG patients in China.METHODS We recruited patients with chronic non-atrophic or mild-to-moderate atrophic gastritis with erosion based on endoscopy and pathology.Patients and treating physicians completed a questionnaire regarding history,endoscopic findings,and treatment plans as well as a follow-up questionnaire to investigate changes in symptoms after 4 wk of treatment.RESULTS Three thousand five hundred sixty-three patients from 42 centers across 24 cities in China were included.Epigastric pain(68.0%),abdominal distension(62.6%),and postprandial fullness(47.5%)were the most common presenting symptoms.Gastritis was classified as chronic non-atrophic in 69.9%of patients.Among those with erosive lesions,72.1%of patients had lesions in the antrum,51.0%had multiple lesions,and 67.3%had superficial flat lesions.In patients with epigastric pain,the combination of a mucosal protective agent(MPA)and proton pump inhibitor was more effective.For those with postprandial fullness,acid regurgitation,early satiety,or nausea,a MPA appeared more promising.CONCLUSION CEG is a multifactorial disease which is common in Asian patients and has non-specific symptoms.Gastroscopy may play a major role in its detection and diagnosis.Treatment should be individualized based on symptom profile.

A primary intestinal lymphangiectasia patient diagnosed by capsule endoscopy and confirmed at surgery: A case report

Intestinal lymphangiectasia （IL） is a rare disease characterized by dilated lymphatic vessles in the intestinal wall and small bowel mesentery which induce loss of protein and lymphocytes into bowel lumen. Because it most often occurs in the intestine and cannot be detected by upper gastroendoscopy or colonoscopy, and the value of common image examinations such as X-ray and computerized tomography （CT） are limited, the diagnosis of IL is difficult, usually needing the help of surgery. Capsule endoscopy is useful in diagnosing intestinal diseases, such as IL. We here report a case of IL in a female patient who was admitted for the complaint of recurrent edema accompanied with diarrhea and abdominal pain over the last twenty years, and aggravated ten days ago. She was diagnosed by M2A capsule endoscopy as a primary IL and confirmed by surgical and pathological examination.

Single-center experience of 309 consecutive patients with obscure gastrointestinal bleeding

AIM: To investigate the diagnostic yield of capsule endoscopy (CE) in patients with obscure gastrointestinal bleeding (OGIB), and to determine whether the yield was affected by different bleeding status. METHODS: Three hundred and nine consecutive patients (all with recent negative gastric and colonic endoscopy results) were investigated with CE; 49 cases with massive bleeding and 260 cases with chronic recurrent overt bleeding. Data regarding OGIB were obtained by retrospective chart review and review of an internal database of CE fi ndings.RESULTS: Visualization of the entire small intestine was achieved in 81.88% (253/309) of cases. Clinically positive findings occurred in 53.72% (166/309) of cases. The positivity of the massive bleeding group was slightly higher than that of the chronic recurrent overt bleeding group but there was no significant difference (59.18% vs 52.69%, P > 0.05) between the two groups. Small intestinal tumors were the most common fi nding in the entire cohort, these accounted for 30% of clinically signifi cant lesions. In the chronic recurrent overt bleeding group angioectasia incidence reached more than 29%, while in the massive bleedinggroup, small intestinal tumors were the most common finding at an incidence of over 51%. Increasing patient age was associated with positive diagnostic yield of CE and the findings of OGIB were different according to age range. Four cases were compromised due to the capsule remaining in the stomach during the entire test, and another patient underwent emergency surgery for massive bleeding. Therefore, the complication rate was 1.3%. CONCLUSION: In this study CE was proven to be a safe, comfortable, and effective procedure, with a high rate of accuracy for diagnosing OGIB.

Diagnostic effect of capsule endoscopy in 31 cases of subacute small bowel obstruction

AIM： TO evaluate the effectiveness and safety of capsule endoscopy （CE） in patients with recurrent subacute small bowel obstruction.METHODS： The study was a retrospective analysis of 31 patients referred to hospital from January 2003 to August 2008 for the investigation of subacute small bowel obstruction, who underwent CE. The patients were aged 9-81 years, and all of them had undergone gastroscopy and colonoscopy previously. Some of them received abdominal computed tomography or small bowel follow-through.RESULTS： CE made a definitive diagnosis in 12 （38.7%） of 31 cases： four Crohn＇s disease （CD）, two carcinomas, one intestinal tuberculosis, one ischemic enteritis, one abdominal cocoon, one duplication of the intestine,one diverticulum and one ileal polypoid tumor. Capsule retention occurred in three （9.7%） of 31 patients, and was caused by CD （2） or tumor （1）. Two with retained capsules were retrieved at surgery, and the other one of the capsules was spontaneously passed the stricture by medical treatment in 6 too. No case had an acute small bowel obstruction caused by performance of CE.CONCLUSION： CE provided safe and effective visualization to identify the etiology of a subacute small bowel obstruction, especially in patients with suspected intestinal tumors or CD, which are not identified by routine examinations.

Palmitoylation in Crohn’s disease:Current status and future directions

S-palmitoylation is one of the most common post-translational modifications in nature;however,its importance has been overlooked for decades.Crohn’s disease(CD),a subtype of inflammatory bowel disease(IBD),is an autoimmune disease characterized by chronic inflammation involving the entire gastrointestinal tract.Bowel damage and subsequent disabilities caused by CD are a growing global health issue.Well-acknowledged risk factors for CD include genetic susceptibility,environmental factors,such as a westernized lifestyle,and altered gut microbiota.However,the pathophysiological mechanisms of this disorder are not yet comprehensively understood.With the rapidly increasing global prevalence of CD and the evident role of S-palmitoylation in CD,as recently reported,there is a need to investigate the relationship between CD and S-palmitoylation.In this review,we summarize the concept,detection,and function of S-palmitoylation as well as its potential effects on CD,and provide novel insights into the pathogenesis and treatment of CD.

Fuel source shift or cost reduction:Context-dependent adaptation strategies in closely related Neodon fuscus and Lasiopodomys brandtii against hypoxia

Oxygen is essential for most life forms.Insufficient oxygen supply can disrupt homeostasis and compromise survival,and hypoxia-induced cardiovascular failure is fatal in many animals,including humans.However,certain species have adapted and evolved to cope with hypoxic environments and are therefore good models for studying the regulatory mechanisms underlying responses to hypoxia.Here,we explored the physiological and molecular responses of the cardiovascular system in two closely related hypoxiaadapted species with different life histories,namely,Qinghai voles(Neodon fuscus)and Brandt’s voles(Lasiopodomys brandtii),under hypoxic(10%O_(2) for 48 h)and normoxic(20.9%O_(2) for 48 h)exposure.Kunming mice(Mus musculus)were used for comparison.Qinghai voles live in plateau areas under hypoxic conditions,whereas Brandt’s voles only experience periodic hypoxia.Histological and hematological analyses indicated a strong tolerance to hypoxia in both species,but significant cardiac tissue damage and increased blood circulation resistance in mice exposed to hypoxia.Comparative transcriptome analysis revealed enhanced oxygen transport efficiency as a coping mechanism against hypoxia in both N.fuscus and L.brandtii,but with some differences.Specifically,N.fuscus showed upregulated expression of genes related to accelerated cardiac contraction and angiogenesis,whereas L.brandtii showed significant up-regulation of erythropoiesis-related genes.Synchronized upregulation of hemoglobin synthesis-related genes was observed in both species.In addition,differences in cardiometabolic strategies against hypoxia were observed in the rodents.Notably,M.musculus relied on adenosine triphosphate(ATP)generation via fatty acid oxidation,whereas N.fuscus shifted energy production to glucose oxidation under hypoxic conditions and L.brandtii employed a conservative strategy involving down-regulation of fatty acid and glucose oxidation and a bradycardia phenotype.In conclusion,the cardiovascular systems of N.fuscus and L.brandtii have evolved different adaptation strategies to enhance oxygen transport capacity and conserve energy under hypoxia.Our findings suggest that the coping mechanisms underlying hypoxia tolerance in these closely related species are context dependent.

Effect of small bowel preparation with simethicone on capsule endoscopy

Background： Capsule endoscopy is a novel non-invasive method for visualization of the entire small bowel. The diagnostic yield of capsule endoscopy depends on the quality of visualization of the small bowel mucosa and its complete passage through the small bowel. To date, there is no standardized protocol for bowel preparation before capsule endoscopy. The addition of simethicone in the bowel preparation for the purpose of reducing air bubbles in the intestinal lumen had only been studied by a few investigators. Methods： Sixty-four participants were randomly divided into two groups to receive a bowel preparation of polyethylene glycol （PEG） solution （Group 1） and both PEG solution and simethicone （Group 2）. The PEG solution and sime- thicone were taken the night before and 20 rain prior to capsule endoscopy, respectively. Frames taken in the small intestine were examined and scored for luminal bubbles by two professional capsule endoscopists. Gastric emptying time and small bowel transit time were also recorded. Results： Simethicone significantly reduced luminal bubbles both in the proximal and distal small intes- tines. The mean time proportions with slight bubbles in the proximal and distal intestines in Group 2 were 97.1% and 99.0%, respectively, compared with 67.2% （P〈0.001） and 68.8% （P〈0.001） in Group 1. Simethicone had no effect on mean gastric emptying time, 32.08 rain in Group 2 compared with 30.88 min in Group 1 （P=0.868）, but it did increase mean small intestinal transit time from 227.28 to 281.84 rnin （P=0.003）. Conclusion： Bowel preparation with both PEG and simethicone significantly reduced bubbles in the intestinal lumen and improved the visualization of the small bowel by capsule endoscopy without any side effects observed.