Molecular mechanism of high altitude hypoxia induced intestinal homeostasis imbalance and research progress of traditional Chinese medicine / 中国临床药理学与治疗学

Hypoxia is one of the factors restricting the survival of people at high altitudes, which can cause various symptoms such as vomiting, diarrhea, palpitations, shortness of breath and acute coma. About 80% of patients with acute mountain sickness have at least one symptom of a gastrointestinal distress (e. g., anorexia, nausea, diarrhea, vomiting, etc.). The pathological characteristics, pathogenesis and drug treatment of intestinal injury caused by high-altitude hypoxia were studied, which is conducive to the diagnosis and treatment of plateau gastrointestinal diseases. Therefore, by summarized relevant literature and systematically expounds the related researches on intestinal damage caused by high altitude hypoxia. We summarized the changes of intestinal morphology, intestinal cells, intestinal flora and other intestinal homeostasis caused by high altitude hypoxia, the mechanism of intestinal inflammation and oxidative damage, and the treatment of traditional Chinese medicine, which provide reference and information for reference for scientific research workers and clinicians.

Effect of mechanical stimulation by rubbing abdomen by interfering with Th17 cell function on intestinal homeostasis in IBS-C model mice / 国际生物医学工程杂志

Objective:To investigate the possible mechanism of rubbing abdomen to regulate intestinal homeostasis in irritable bowel syndrome with constipation (IBS-C) mouse models.Methods:IBS-C mouse models of intestinal immune dysfunction were established using trinitrobenzene sulfonic acid (TNBS)-induced C57BL/J6 male mice. Thirty C57BL/J6 mice were randomly divided into three groups: the control group, the model group, and the mogul group. After 7 days of modeling, mice in the mogul group were given a mogul mechanical stimulation intervention once per day for 2 weeks, while mice in the control and model groups were not given any intervention. Changes in serum levels of interleukin-6 (IL-6) and IL-17A were detected by enzyme-linked immune sorbent assay (ELISA) and immunohistochemistry. The gene expression and protein levels of IL-17A and IL-23 were detected by quantitative real-time fluorescence PCR (qRT-PCR) and Western Blot, respectively. The morphological changes were observed by HE staining. The CD44 and CD62L expression changes were observed by immunofluorescence staining.Results:Compared with the model group, the levels of IL-6 and IL-17A in the serum of mice in the mogul group were decreased, and the expression of IL-6 and IL-7A in the tissues was down-regulated (all P<0.001). In addition, the gene expression and protein expression levels of IL-17A and IL-13 in the tissues of mice in the mogul group were decreased (all P<0.001). HE staining results showed that the mogul mechanical stimulation intervention could repair colonic tissues and reduce the inflammatory response. Immunofluorescence staining results showed that mogul mechanical stimulation intervention could downregulate the expression of CD44 but had no modulating effect on the expression of CD62L. Conclusions:Rubbing abdomen can improve intestinal homeostasis in IBS-C model mice by regulating changes in Th17 cell function.

Research Progress of NGAL in Inflammatory Bowel Disease / 胃肠病学

Inflammatory bowel disease (IBD) is a chronic and recurrent inflammatory disease of gastrointestinal tract, including Crohn's disease and ulcerative colitis. The exact etiology and pathogenesis of IBD are still not clear. Neutrophil gelatinase-associated lipocalin (NGAL) plays an important role in regulating intestinal immunity, maintaining intestinal epithelial cell barrier, and coordinating the composition of intestinal flora. In addition, NGAL is useful for helping the clinical testing of IBD. This article reviewed the research progress of NGAL in IBD.

Research progress on the effect of high-fat diet on intestinal homeostasis via microbial metabolites / 中华临床营养杂志

Intestinal homeostasis is affected by many factors such as genetics, environment, and eating habits. High-fat diet, as one of the influencing factors, may affect the intestinal microbial metabolites, destroy the integrity of the intestinal mucosal barrier and induce intestinal immunity dysfunction, which in turn leads to imbalance of intestinal homeostasis and occurrence of digestive diseases. This article reviews the recent research progress on the effects of high-fat diet on intestinal homeostasis via microbial metabolites.

Effect of mTORC1 on intestinal group 3 innate lymphocytes function / 上海交通大学学报（医学版）

Objective : To investigate the effect of mechanistic target of rapamycin complex 1 (mTORC1) on group 3 innate lymphoid cells (ILC3) function. Methods ¡¤ Intestinal lamina propria leukocytes (LPL) of C57BL/6 wild type mice were stimulated by rapamycin, the specific inhibitor of mTORC1 signaling pathway, in vitro, and then quantity and function of ILC3 were detected by flow cytometry. Next, purified ILC3 from mice intestinal LPL were sorted by flow cytometry. After the activation of ILC3 with IL-23, mRNA expression levels of Rorc (the gene encoding retinoic acid receptor related orphan receptor, i.e. RORγt), Il22 and Rptor (the gene encoding key component protein of mTORC1, i.e. Raptor) were detected by real-time qPCR. For further study, a genetically engineered mouse model specifically knocked out Raptor in ILC3 was constructed. Effects of mTORC1 loss on the quantity and function of ILC3 as well as gut structure were detected by flow cytometry, real-time qPCR and hematoxylin-eosin staining. Results ¡¤ The total ILC3 number had no change, but the secretion of IL-22 by ILC3 reduced after stim-ulation with rapamycin. Il22, Rorc and Rptor mRNA expression levels were upregulated simultaneously in ILC3 after activation with IL-23. In addition, there was no significant difference in the numbers and proportions of total ILC3 and ILC3 subsets as well as gut structure in Rap-tor-deficient mice, but the cytokine IL-22 secretion level of ILC3 significantly decreased in these mice. Conclusion ¡¤ Loss of mTORC1 func-tion inhibits ILC3 from secreting IL-22 but has no effect on the intestinal structure and intestinal ILC3 development, which reveals the positive regulation of mTORC1 signaling on intestinal ILC3 function.

Clinical diagnosis and treatment of intestinal complications after renal transplantation / 器官移植

Objective To investigate the etiology, clinical characteristics, diagnosis and treatment of intestinal complications after renal transplantation. Methods Clinical data of 47 patients presenting with intestinal complications following renal transplantation were retrospectively analyzed. The etiology, clinical characteristics and treatment experience of intestinal complications were summarized. Results Forty-seven patients with intestinal complications after renal transplantation were followed up for 3-36 months with the median time of 18 months. Intestinal complications included the upper gastrointestinal bleeding in 4 cases, the lower gastrointestinal bleeding in 1 case, acute enteritis in 25 cases, chronic enteritis in 12 cases, intestinal tuberculosis in 1 case, colon cancer in 1 case, and intestinal obstruction in 3 cases, respectively. Among patients with gastrointestinal bleeding, the symptoms occurred after the use of high-dose adrenal cortex hormone in 4 cases and 2 patients developed hemorrhagic shock. In patients with acute enteritis, 7 cases received immunosuppressants for the first time during the perioperative period of renal transplantation, the remaining18 patients had dirty diet or catched cold and 4 were positive for pathogens. Among patients with chronic enteritis,plasma concentrations of mycophenolic acid or tacrolimus were elevated in 12 patients, water, electrolyte, and acidbase imbalance was detected, 2 were positive for pathogens, and 8 were accompanied with severe anemia. One case of intestinal obstruction occurred during the perioperative period of renal transplantation, and 2 cases experienced toxic shock. According to the type and severity of disease, symptomatic and etiological treatments were actively implemented.In the 47 patients, 45 were cured and 2 died from the lower gastrointestinal bleeding and respiratory failure caused by lung metastasis of colon cancer. Three patients suffered from transplanted renal insufficiency. Conclusions The intestinal complications after renal transplantation are diverse, which are correlated with the imbalance of intestinal homeostasis.Both the acute and chronic diseases can cause various degrees of damage to the function of transplanted kidneys. Clinical prognosis is poor at the presence of severe complications. Active prevention and management should be implemented to reduce the risk of postoperative complications and enhance the cure rate.

Th17/Treg balance in inflammatory bowel disease / 国际儿科学杂志

Inflammatory bowel disease(IBD) is characterized by chronic non-specific inflammatory dis ease.The inflammation caused by abnormal immune response in intestinal mucosa exerts an important role in the pathogenesis of IBD.T helper 17 cells(Th17)are involved in the development of chronic inflammation and auto immune disease,whereas regulatory T cells can inhibit the function of autoimmune,and thus the balance of Th17/Treg balance plays an important role in intestinal homeostasis.Various strategies can be done to modulate Th17/Treg balance,such as antigen-presenting cells,microoganisms,some key molecules,natural compounds,proving a promising therapeutic method for IBD.

Advances in Study on Intestinal Microbiota in Intestinal Homeostasis and Inflammatory Bowel Disease / 胃肠病学

Inflammatory bowel disease(IBD),including ulcerative colitis(UC)and Crohn’s disease(CD),is characterized by chronic non-specific inflammation of intestinal tract,which is incurable and easily relapsing. Recently,the role of gut microbiota in IBD has become a hot spot of study. This article reviewed the advances in study on intestinal microbiota in intestinal homeostasis and IBD.

Regulation of Intestinal Homeostasis by Innate Immune Cells

The intestinal immune system has an ability to distinguish between the microbiota and pathogenic bacteria, and then activate pro-inflammatory pathways against pathogens for host defense while remaining unresponsive to the microbiota and dietary antigens. In the intestine, abnormal activation of innate immunity causes development of several inflammatory disorders such as inflammatory bowel diseases (IBD). Thus, activity of innate immunity is finely regulated in the intestine. To date, multiple innate immune cells have been shown to maintain gut homeostasis by preventing inadequate adaptive immune responses in the murine intestine. Additionally, several innate immune subsets, which promote Th1 and Th17 responses and are implicated in the pathogenesis of IBD, have recently been identified in the human intestinal mucosa. The demonstration of both murine and human intestinal innate immune subsets contributing to regulation of adaptive immunity emphasizes the conserved innate immune functions across species and might promote development of the intestinal innate immunity-based clinical therapy.