Mechanism of Qingfei Huatan Zhuyu Decoction in Treatment of COPD Based on "Lung and Intestinal Co-treatment" / 中国实验方剂学杂志

ObjectiveTo observe the effect of Qingfei Huatan Zhuyu decoction on the lung and intestinal function of rats with chronic obstructive pulmonary diseases （COPD） and explore the deep-seated mechanism of its embodiment of lung and intestinal co-treatment. MethodA total of 60 Wistar rats were randomly divided into six groups， with 10 rats in each group， and the groups were control group， model group， acute syrup group （10 g·kg-1·d-1）， and low， medium， and high-dose groups （10， 15， 20 g·kg-1·d-1） of Qingfei Huatan Zhuyu decoction. The COPD rat model was established by lipopolysaccharide tracheal drip combined with the smoke inhalation method， and the acute syrup group and the Qingfei Huatan Zhuyu decoction group were administered by gavage with corresponding dose concentrations respectively， while the rest groups were controlled by saline gavage， and the lung function and blood gas indexes of rats were monitored after the last administration. The histopathological changes in the lung and intestine were observed microscopically. The expression of serum interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and secretory immunoglobulin A （IgA） in colon tissue were measured by enzyme-linked immunosorbent assay （ELISA）. The biochemical indexes such as serum diamine oxidase （DAO）， D-lactic acid， and malondialdehyde （MDA） were measured. Immunohistochemistry was used to detect the expression of tight junction protein （Occludin） in rat colon tissue. The expression of F4/80 positive alveolar macrophages in rat lung tissue， and the expression of α-actin （α-SMA） and colonic atresia small band protein-1 （ZO-1） were determined by immunofluorescence. The protein expression of p-NF-κB p65， NF-κB p65， p-p38 MAPK， and p-p38 MAPK and the expression of Occludin and ZO-1 in colon tissue were detected in rat lung tissue by Western blot. ResultCompared with the normal group， the model group had pulmonary dysfunction， reduced forced vital capacity （FVC）， arterial partial oxygen pressure （PaO2）， arterial oxygen saturation （SaO2）， and dynamic lung compliance （Cdyn） （P<0.01）， and the pathological changes in the lung and intestine were obvious. The expressions of IL-6， TNF-α， DAO， D-lactic acid， and MDA in serum were increased （P<0.05，P<0.01）， and the protein expression ratio of p-NF-κB p65/NF-κB p65 and p-p38 MAPK/p38 MAPK in lung tissue was increased. The expression of F4/80 positive macrophages in lung tissue was enhanced. The expression of IgA， Occludin， and ZO-1 in colon tissue decreased （P<0.05，P<0.01）. Compared with the model group， the pulmonary function of the rats in the acute syrup group and groups of Qingfei Huatan Zhuyu decoction was significantly improved， and the FVC， PaO2， SaO2， and Cdyn were increased （P<0.05， P<0.01）. The pathological changes in the lung and intestine were significant. The expressions of IL-6， TNF-α， DAO， D-lactic acid， and MDA in serum were decreased （P<0.05，P<0.01）， and the expressions of F4/80 positive macrophages in lung tissue were decreased （P<0.01）. The protein expression ratio of p-NF-κB p65/NF-κB p65 and p-p38 MAPK/p38 MAPK in lung tissue decreased （P<0.01）， and the expression of IgA， Occludin， and ZO-1 in colon tissue increased （P<0.01）. ConclusionQingfei Huatan Zhuyu decoction can effectively reduce the symptoms of COPD rats， and its mechanism of action is related to inhibiting the inflammatory response of lung tissue and improving the barrier function of the intestinal mucosa.

Pachymic acid protects against Crohn's disease-like intestinal barrier injury and colitis in miceby suppressingintestinal epithelial cell apoptosis via inhibiting PI3K/AKT signaling / 南方医科大学学报

OBJECTIVE@#To investigate the effect of pachymic acid (PA) against TNBS-induced Crohn's disease (CD)-like colitis in mice and explore the possible mechanism.@*METHODS@#Twenty-four C57BL/6J mice were randomized equally into control group, TNBS-induced colitis model group and PA treatment group. PA treatment was administered via intraperitoneal injection at the daily dose of 5 mg/kg for 7 days, and the mice in the control and model groups were treated with saline. After the treatments, the mice were euthanized for examination of the disease activity index (DAI) of colitis, body weight changes, colon length, intestinal inflammation, intestinal barrier function and apoptosis of intestinal epithelial cells, and the expressions of TNF-α, IL-6 and IL-1β in the colonic mucosa were detected using ELISA. The possible treatment targets of PA in CD were predicted by network pharmacology. String platform and Cytoscape 3.7.2 software were used to construct the protein-protein interaction (PPI) network. David database was used to analyze the GO function and KEGG pathway; The phosphorylation of PI3K/AKT in the colonic mucosal was detected with Western blotting.@*RESULTS@#PA significantly alleviated colitis in TNBS-treated mice as shown by improvements in the DAI, body weight loss, colon length, and histological inflammation score and lowered levels of TNF-α, IL-6 and IL-1β. PA treatment also significantly improved FITC-dextran permeability, serum I-FABP level and colonic transepithelial electrical resistance, and inhibited apoptosis of the intestinal epithelial cells in TNBS-treated mice. A total of 248 intersection targets were identified between PA and CD, and the core targets included EGFR, HRAS, SRC, MMP9, STAT3, AKT1, CASP3, ALB, HSP90AA1 and HIF1A. GO and KEGG analysis showed that PA negatively regulated apoptosis in close relation with PI3K/AKT signaling. Molecular docking showed that PA had a strong binding ability with AKT1, ALB, EGFR, HSP90AA1, SRC and STAT3. In TNBS-treated mice, PA significantly decreased p-PI3K and p-AKT expressions in the colonic mucosa.@*CONCLUSION@#PA ameliorates TNBS-induced intestinal barrier injury in mice by antagonizing apoptosis of intestinal epithelial cells possibly by inhibiting PI3K/AKT signaling.

Autophagy-regulated strategies in pre-clinical studies of inflammatory bowel disease / 药学学报

Inflammatory bowel disease (IBD) is a group of chronic idiopathic colorectal inflammatory diseases with a progressive and unpredictable course, including ulcerative colitis (UC) and Crohn's disease (CD). Abnormal intestinal inflammation and immune response contribute to the pathogenesis of IBD. Autophagy as an essential catabolic process in cells, has been demonstrated to have associations with a variety of inflammatory diseases including IBD. Here, we review the relationship between autophagy dysfunction and the process of IBD. The progress of several autophagy regulators for intestinal epithelial cells and macrophages is highlighted (inflammasome inhibitors, intestinal flora regulators, and other signal regulators) in the current studies on IBD.

Guiqi Baizhu Prescription Combined with Oxaliplatin Protects Intestinal Barrier of Tumor-bearing Mice with Gastric Cancer by Regulation of VIP/cAMP/PKA/AQP Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the protective effect of Guiqi Baizhu prescription combined with oxaliplatin on the intestinal barrier of tumor-bearing mice with gastric cancer by regulating downstream aquaporin 3 （AQP3） and aquaporin 4 （AQP4） through the vasoactive intestinal peptide （VIP）/cyclic adenosine monophosphate （cAMP）/protein kinase A （PKA） signaling pathway. MethodThe gastric cancer cell lines MFC with a density of 1×107/mL were prepared into cell suspension. The tumor-bearing mouse model of gastric cancer was established by inoculating 0.2 mL cell suspension under the right axilla of mice. After successful modeling， mice were randomly divided into 5 groups， namely， model group， oxaliplatin group （10 mg·kg-1）， and high， medium， and low-dose oxaliplatin + Guiqi Baizhu prescription groups （17.68， 8.84， 4.42 g·kg-1）， with 10 mice in each group， and the remaining 10 mice were set as a blank group. Mice in each group were treated with Chinese medicine， oxaliplatin， or normal saline by gavage or intraperitoneal injection for 14 d. The next day after the last dose， blood was taken from the eyeball to separate serum and take colonic samples. Hematoxylin-eosin （HE） staining was used to observe the changes in tissue morphology. The content of D-lactate acid （D-LA） and diamine oxidase （DAO） in the serum was determined by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expressions of VIP， cAMP， PKA， AQP3， and AQP4 were detected by Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultCompared with the blank group， the model group showed edema in the colonic submucosa， disordered arrangement of intestinal glands in the mucosal layer， loss of goblet cells， infiltration of inflammatory cells， and villus shedding. However， there were different degrees of improvement in each administration group. As compared with the blank group， the serum levels of DAO and D-LA in the model group were significantly increased （P<0.01）. As compared with the model group， the levels of DAO and D-LA in the high-dose oxaliplatin + Guiqi Baizhu prescription group and the level of D-LA in the medium-dose oxaliplatin + Guiqi Baizhu prescription group were decreased （P<0.05， P<0.01）. As compared with the oxaliplatin group， the levels of D-LA in the high and medium-dose oxaliplatin + Guiqi Baizhu prescription groups were decreased （P<0.05）， and the levels of DAO and D-LA in other administration groups were decreased as well， but the difference had no statistical significance. As compared with the blank group， the mRNA and protein expression levels of VIP， cAMP， PKA， AQP3， and AQP4 in the model group were significantly decreased （P<0.05， P<0.01）. As compared with the model group， the mRNA and protein expression levels of VIP， cAMP， PKA， AQP3， and AQP4 in each administration group were increased， and those in the high-dose oxaliplatin + Guiqi Baizhu prescription group were significantly increased （P<0.05， P<0.01）， while the protein expression level of cAMP in the medium-dose oxaliplatin + Guiqi Baizhu prescription group were increased （P<0.05）. As compared with the oxaliplatin group， the protein expression levels of cAMP in the high-dose oxaliplatin + Guiqi Baizhu prescription group were increased （P<0.05）， and the mRNA and protein expressions of these indexes in the other groups were also increased but the differences were not statistically significant. ConclusionGuiqi Baizhu prescription combined with oxaliplatin can regulate AQP3 and AQP4 through the VIP/cAMP/PKA signaling pathway to protect the intestinal barrier of tumor-bearing mice with gastric cancer.

Effect of Zishenwan on Intestinal Barrier and Transcriptome of Skeletal Muscle of db/db Diabetic Mice / 中国实验方剂学杂志

ObjectiveTo explore the effect of Zishenwan on glucose and lipid metabolism in spontaneous type 2 diabetes （db/db） mice and investigate the underlying mechanism for improving diabetes based on intestinal barrier function and skeletal muscle transcriptome sequencing results. MethodLiquid chromatography-tandem mass spectrometry （LC-MS/MS） was used to analyze the components of Zishenwan. Sixteen 6-week-old db/db mice were divided into a model group and a Zishenwan group， while eight wild-type mice were assigned to the normal group. The Zishenwan group received oral administration of drugs for six weeks， during which fasting blood glucose， body weight， and food intake were measured. Serum total cholesterol （TC） and triglyceride （TG） levels were determined， and fasting insulin levels were measured to calculate the homeostatic model assessment of insulin resistance （HOMA-IR）. After the treatment， skeletal muscle and ileum tissues were collected， followed by hematoxylin-eosin （HE） staining. Immunohistochemistry was used to detect the expression of tight junction proteins occludin and zonula occludens-1 （ZO-1） in the ileum. Transcriptome sequencing was performed to detect the skeletal muscle transcriptome， and enrichment analysis was conducted for differentially expressed genes. ResultMultiple active components were identified in Zishenwan. Compared with the normal group， the model group showed increased fasting blood glucose， body weight， TC， TG， and HOMA-IR （P<0.01）. Compared with the model group， Zishenwan significantly reduced fasting blood glucose， body weight， TC， TG， and HOMA-IR in db/db mice （P<0.01）， while there was no statistically significant difference in food intake. Compared with the normal group， the model group exhibited lipid deposition in skeletal muscle， as well as structural changes in the ileum， with significant decreases in the protein expression levels of intestinal occludin and ZO-1 （P<0.01）. Compared with the model group， Zishenwan improved the pathological changes in skeletal muscle and ileum， and increased the protein expression of occludin and ZO-1 in the ileum （P<0.01）. Transcriptome analysis suggested that Zishenwan might improve skeletal muscle metabolism and increase insulin sensitivity in mice. ConclusionZishenwan can improve glucose and lipid metabolism in db/db mice， and this effect may be related to its protection of intestinal barrier function and transcriptional regulation of skeletal muscle metabolism-related genes.

The mechanism of cilostazole alleviating intestinal mucosal barrier dysfunction in type 2 diabetic mice / 西安交通大学学报(医学版)

【Objective】 To explore the effect of cilostazol on intestinal barrier function in type 2 diabetes (T2DM). 【Methods】 The GSE142153 dataset was downloaded from GEO database to analyze gene changes in diabetic patients. Eight-week-old male db/db mice and control m/m mice were randomly divided into m/m+cmc, m/m+cilo, db/db+cmc, and db/db+cilo groups. Mice in different groups were given cilostazol and corresponding solvents for 4 weeks. We detected the levels of serum sCD40L and the expression of CD40 in intestinal tissue, and evaluated the mice’s intestinal barrier function by examining intestinal permeability, water content, bacterial number, and tight junction protein expression in different groups. 【Results】 Differential expressed genes were enriched in platelet activation and endothelial barrier function pathways in diabetic patients. Compared with those in the control group, the levels of serum sCD40L in db/db diabetic mice elevated significantly, and the CD40 expression, permeability, water content and bacterial number in intestinal tissue increased obviously, while the expression of tight junction protein decreased. Cilostazol treatment in diabetic mice decreased the levels of serum sCD40L and CD40, and alleviated significantly the intestinal barrier dysfunction. 【Conclusion】 Cilostazol attenuated the damage of intestinal barrier function in T2DM, and its protective effect may be related to the inhibition of platelet activation in diabetic mice.

KHK involved in intestinal barrier impairment by high-fat and high-fructose diet / 西安交通大学学报(医学版)

【Objective】 To explore the effect of high-fat and high-fructose diet on mouse intestinal barrier function, as well as the role of ketohexokinase (KHK), the key enzyme in fructose metabolism, in intestinal barrier impairment. 【Methods】 Eight-week-old male control C57BL/6J mice and Khk-/- mice were randomly divided into control + normal diet (ND), control + high-fat and high-fructose diet (HFHFD), Khk-/-+ normal diet (ND+Khk-/-), and Khk-/-+ high-fat and high-fructose diet (HFHFD+Khk-/-) groups, with eight mice in each group. During the high-fat and high-fructose diet and normal diet, the body weight changes of mice in different groups were recorded. After the intervention, the blood glucose and insulin levels of mice in each group were detected. The intestinal barrier function and inflammation level of mice were evaluated by detecting intestinal water content, permeability, tight junction protein expression, serum and intestinal inflammatory factor levels. 【Results】 Compared with ND group, HFHFD group significantly increased the body weight, blood glucose and insulin levels of mice, increased the intestinal water content and permeability, decreased the expression of tight junction proteins, and increased inflammatory factors of the serum and intestines. In the two groups fed with high-fat and high-fructose diet, the body weight, blood glucose and insulin levels of the HFHFD+Khk-/- group were significantly lower than those of HFHFD group, and the intestinal barrier dysfunction and inflammation were significantly improved. 【Conclusion】 KHK, a key enzyme in fructose metabolism, is involved in the impairment of intestinal barrier caused by high-fat and high-fructose diet. Knockout of Khk gene significantly improved intestinal barrier dysfunction and the inflammation level.

Effects of heat stress on intestinal tract and cognitive function / 环境与职业医学

Heat stress refers to a series of stress reactions such as heat balance disturbance and physiological dysfunction when the body is exposed to the thermal environment for a long time. Studies have found that heat stress can damage intestinal morphology, such as length of intestinal villi, number of goblet cells, and depth of the crypt, affecting the digestion and absorption functions. It also can increase the permeability of the intestinal barrier by damaging the tight junction of the intestinal epithelium, which in turn allows endotoxin and bacteria to enter the blood circulation from the intestinal cavity to cause a systemic inflammatory response. At the same time, heat stress can disrupt the homeostasis of intestinal microbiota, increase pathogenic bacteria, and change downstream metabolites such as short-chain fatty acids. In addition, heat stress can inhibit the occurrence of hippocampal neurons and reduce the number of neurons; decrease the density of synapses; damage important organelles of neurons; induce inflammation of the central nervous system, and then lead to cognitive dysfunction. The brain-gut axis is a two-way signal axis between the intestine and the brain. Intestinal microorganisms and the intestinal barrier can participate in central nervous system regulation, and the brain can change the intestinal homeostatic function and affect the quality of the intestinal barrier through the hypothalamic-pituitary-adrenal axis (HPA axis). The interaction plays an essential role in the body's homeostasis. Therefore, this article reviewed current understandings on the impacts of heat stress on the gut and cognitive function, aiming to provide a reference for subsequent research.

Exploring on Mechanism of Gegen Qinliantang in Interventing Antibiotic-associated Diarrhea Based on 16S rRNA Sequencing and Network Pharmacology / 中国实验方剂学杂志

ObjectiveTo investigate the mechanism of Gegen Qinliantang（GQT） on the intestinal flora of antibiotic-associated diarrhea（AAD） by 16S rRNA sequencing and network pharmacology. MethodSixty SD rats were randomly divided into six groups（n=10）， including blank group， model group， GQT high-， medium- and low-dose groups（10.08， 5.04， 2.52 g·kg-1） as well as Lizhu Changle group（0.15 g·kg-1）， except for the blank group， each group was given clindamycin（250 mg·kg-1） by gavage once a day for 7 consecutive days. After successful modeling， the blank group and the model group were given equal volumes of normal saline by gavage. The other groups were given corresponding doses of drugs by gavage for 14 days. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） was used to screen the active components and targets of GQT， GeneCards， Online Mendelian Inheritance in Man（OMIM） database， Pharmacogenetics and Pharmacogenomics Knowledge Base（PharmGKB）， DrugBank and DisGeNET were used to search for AAD disease targets. The drug-disease common targets were obtained by R software. STRING was applied to analyze the target protein-protein interaction， and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis was performed. Then hematoxylin-eosin（HE） staining was used to observe the pathological changes of the colon， and 16S rRNA sequencing of AAD colon content flora structure further verified the results of network pharmacology. ResultThrough network pharmacology， it was found that 238 active components were screened from GQT and acted on 276 component targets， among which quercetin， puerarin， wogonin and apigenin were the main core components of GQT， 1 097 AAD disease targets and 127 drug-disease intersection targets. The protein-protein interaction network mainly included core targets such as protein kinase B1（Akt1）， interleukin（IL）-6 and IL-1β， which were mainly enriched in the IL-17 signaling pathway. It was verified through animal experiments that compared with the blank group， the colon structure of the model group was seriously abnormal， the intestinal epithelial columnar cells were damaged， the goblet cells were reduced， and a large number of inflammatory cells were infiltrated. Compared with the model group， the colon structure of the GQT high-dose group improved， but there were still abnormalities， the colon structure of GQT medium- and low- dose groups and Lizhu Changle group improved significantly and reached the normal level. GQT could improve the structural diversity of AAD intestinal flora. At the phylum level， the abundance of Firmicutes was increased and the abundance of Bacteroidetes was decreased. At the genus level， the abundance of Lactobacillus was increased， and the abundances of Prevotella and Bacteroides were decreased. Among them， Lactococcus could be used as a biomarker for AAD treatment with GQT， and the prediction of functional metabolism of intestinal flora revealed that GQT could promote acetate and lactate metabolic pathways in the intestine. ConclusionGQT may activate IL-17 signaling pathway by acting on the targets of Akt1 and IL-6 through key components such as quercetin and wogonin， and improve the abundance of Lactococcus in the intestinal tract as well as acetate and lactate metabolic pathways， so as to play a role in repairing the intestinal barrier for the treatment of AAD.

Chronic psychological stress aggravates intestinal barrier damage and promotes enteritis development through inhibiting Wnt/β-catenin pathway / 中华微生物学和免疫学杂志

Objective:To investigate the mechanism by which chronic psychological stress aggravates intestinal barrier damage and promotes the development of enteritis through inhibiting Wnt/β-catenin pathway, so as to provide a new therapeutic strategy for the clinical diagnosis and treatment of inflammatory bowel disease (IBD).Methods:A comorbidity model of chronic psychological stress and enteritis was established using C57BL/6J mice. HE staining was used to analyze the effects of chronic psychological stress on the intestinal pathological damage in mice with enteritis. ELISA was used to detect the expression of proinflammatory cytokines. The ultrastructural changes of colonic cells and the state of intestinal mucus layer were observed under transmission electron microscope and scanning electron microscope. The secretion of mucoprotein 2 (MUC2) and the expression of cell proliferation marker Ki67 were detected by immunofluo rescence staining. The numbers of goblet cells were detected by Alcian blue-periodic acid-Schiff (AB-PAS) staining. Western blot was performed to analyze the expression of tight junction protein between intestinal epithelial cells, β-catenin which was a key protein of Wnt/β-catenin pathway maintaining crypt proliferation, and downstream protein c-myc.Results:The sugar water consumption ratio decreased, but tail suspension immobility time, the swimming immobility time and the expression of corticotropin releasing hormone (CRH) in hypothalamus increased (all P<0.05) in the stress group as compared with those in the control group. Chronic psychological stress promoted weight loss and colonic shortening in mice with enteritis, exacerbated pathological damage and enhanced the release of pro-inflammatory factors. Moreover, increased disappearance of intestinal epithelial microvilli and severe cellular ultrastructural damage were also observed in the stress+ dextran sulfate sodium salt (DSS) group. There was no pathological damage in the control and stress groups. Chronic psychological stress aggravated intestinal barrier injury and inhibited intestinal barrier repair by inhibiting Wnt/β-catenin pathway. Conclusions:In the mouse model of DSS-induced enteritis, chronic psychological stress preconditioning inhibited the Wnt/β-catenin pathway, weakened the repair ability of intestinal epithelium, aggravated the loss of mucus layer of intestinal barrier and the damage of tight junction structure, and promoted the development of enteritis. In the absence of enteritis, chronic psychological stress had no significant effects on the Wnt/β-catenin pathway and the intestinal barrier.

Parkinson's Disease: A Multisystem Disorder / 神经科学通报·英文版

The way sporadic Parkinson's disease (PD) is perceived has undergone drastic changes in recent decades. For a long time, PD was considered a brain disease characterized by motor disturbances; however, the identification of several risk factors and the hypothesis that PD has a gastrointestinal onset have shed additional light. Today, after recognition of prodromal non-motor symptoms and the pathological processes driving their evolution, there is a greater understanding of the involvement of other organ systems. For this reason, PD is increasingly seen as a multiorgan and multisystemic pathology that arises from the interaction of susceptible genetic factors with a challenging environment during aging-related decline.

Research progress on the relationship between gut-liver axis disorder and sepsis / 中华危重病急救医学

Sepsis is a life-threatening organ dysfunction caused by an uncontrolled host response to infection. The mechanism of sepsis is extremely complicated and the mortality is still high. Persistent researches provide an important way to break through the "bottleneck" of clinical diagnosis and treatment of sepsis. In recent years, more and more studies have shown that gut-liver axis disorders, especially those caused by intestinal dysbiosis, intestinal barrier dysfunction, abnormal liver immune function, and bile acid metabolism disorders, play an important role in the occurrence and development of sepsis. This review describes the research progress of gut-liver axis disorders in the pathogenesis of sepsis for providing new ideas for clinical treatment.

An exploration on the correlation between dietary fiber intake and intestinal barrier function in patients with diarrhea-predominant irritable bowel syndrome / 中华临床营养杂志

Objective:To explore the correlation between dietary fiber intake and intestinal barrier function in patients with irritable bowel syndrome with diarrhea (IBS-D).Methods:IBS-D patients were recruited from May 2019 to October 2019 at the clinic of gastroenterology department in China-Japan Friendship Hospital and healthy controls (HCs) were recruited by advertisement. Clinical manifestations, psychological status and quality of life were assessed using standardized questionnaires. A food frequency questionnaire was used to assess dietary habits in the preceding year. Serum diamine oxidase (DAO) was measured via ELISA.Results:64 IBS-D patients and 35 HCs were enrolled, with no significant difference in sex ratio, age and BMI between the two groups. Second to health concern, food avoidance was the dominant impacting factor for quality of life in IBS-D patients. The intake frequency of dietary fiber was decreased in IBS-D patients, and the intake frequencies of dietary fiber-rich foods were significantly lower in IBS-D patients ( P < 0.01 for tubers, P = 0.002 for vegetables, P = 0.019 for fruits and P = 0.045 for legumes). On the other hand, the intake frequencies of processed meat ( P < 0.01), greasy food ( P = 0.009), barbecued food ( P = 0.002) and animal offal ( P = 0.003) were significantly higher in IBS-D patients compared with HCs, indicating the increased intake frequency of fat. Multivariate logistic regression showed that tubers might reduce the risk of IBS-D ( OR = 0.409,95% CI: 0.232 to 0.722, P = 0.002). The frequency of abdominal pain was positively associated with the intake frequency of greasy food in IBS-D patients. Serum DAO was measured in 37 IBS-D patients and 27 HCs. IBS-D patients had significantly higher serum DAO than HCs ( 77.0 [55.3, 100.6] μg/L vs 42.5 [28.0, 58.2] μg/L, P < 0.01). Among all the participants with serum DAO test results, the level of DAO was negatively associated with the intake frequencies of tubers, vegetables and fruits while positively associated with the intake frequencies of processed meat and barbecued food. Conclusions:Food avoidance was an important impacting factor for quality of life in IBS-D patients. IBS-D patients might have insufficient dietary fiber intake and excessive fat intake. Tubers could possibly reduce the risk of IBS-D. The decreased intake frequency of dietary fiber might have a role in intestinal barrier dysfunction in IBS-D patients.

Research progress on early enteral nutrition in critically ill patients / 中华临床营养杂志

Intestinal barrier function impairment can lead to bacterial and toxin translocation in critically ill patients and is an important factor in gut-derived infections and even multiple organ failure. Early enteral nutrition (EEN) can nourish the intestine, prevent bacterial translocation, effectively maintain intestinal barrier function and immune function and provide metabolic substrates for the body, bringing clinical benefits. For critically ill patients such as those with severe acute pancreatitis, severe burns and severe traumatic brain injury and those after major abdominal surgery, there is evidence-based proof supporting EEN while in patients with uncontrolled shock and severe hypoxemia and acidosis, the initiation of EEN should be delayed. EEN in critically ill patients can be applied orally or through nasogastric tube. Dietary fiber-free intact protein preparations are recommended at initiation and administration via continuous pumping can improve EEN gastrointestinal tolerability.

Effect of pectin on intestinal barrier function in elderly stroke patients / 中华急诊医学杂志

Objective:To explore the effect of pectin on improving intestinal barrier injury in elderly stroke patients.Methods:A total of 60 elderly stroke patients who received enteral nutrition in Department of Critical Care Medicine of Taizhou People's Hospital from November 2020 to October 2021 were included. The control group included 30 cases, using conventional enteral nutrition solution. The other 30 cases were in the study group, and pectin was added on the basis of routine enteral nutrition solution. The levels of serum diamine oxidase (DAO) and D-lactic acid (D-LA) were measured on the first and 7th days of enteral nutrition to evaluate the intestinal barrier function of elderly stroke patients. The levels of interleukin-6 (IL-6), procalcitonin (PCT) and high-sensitivity C-reactive protein (CRP) were measured to evaluate the inflammatory response level of elderly stroke patients. The clinical prognosis of the two groups was compared.Results:Compared with the control group, the values of DAO [(4.05±1.56)ng/mL] and D-LA [(6.11±2.20) μmol/L] in the study group were significantly lower than those in the control group on the 7th day (all P < 0.05). Also the levels of IL-6 [(15.43±12.53) ng/mL], PCT [(0.82±0.98) ng/mL] and CRP [(6.94±6.60) mg/L] in the study group were lower than those in the control group, and the difference between the two groups was statistically significant (all P < 0.05). Compared with the control group, the length of ICU stay and total length of hospital stay in the study group were shorter than those in the control group ( P<0.05), but there was no significant difference in the incidence of stroke-related pneumonia (16.7% vs. 30.0%) and 30-day mortality (16.7% vs. 20.0%) between the two groups ( P>0.05). Conclusions:The enteral nutrition with pectin supplementation can improve intestinal barrier function and reduce inflammatory response in elderly stroke patients.

Research progress on interleukin-10 receptor A in the pathogenesis of inflammatory bowel disease / 中国小儿急救医学

Inflammatory bowel disease(IBD) is a complex multifactorial disease characterized by chronic recurrent intestinal inflammation.The etiology of IBD has not yet been determined, and relevant studies have focused on the genetic susceptibility, immune response, intestinal microbiome and environmental factors of the host.Studies have found that interleukin-10 receptor A(IL-10RA)plays important roles in the pathogenesis of IBD.IL-10RA can not only affect the intestinal barrier, but also affect the intestinal immune system.Furthermore, the mutation of IL-10RA itself is highly correlated with very early-onset IBD.

The combination of berberine and evodiamine ameliorates high-fat diet-induced non-alcoholic fatty liver disease associated with modulation of gut microbiota in rats

Nonalcoholic fatty liver disease (NAFLD) is considered to be a manifestation of hepatic metabolic syndrome. Some studies on the pathogenesis of NAFLD by targeting gut microbiota have attracted wide attention. Previous studies have demonstrated the positive effects of berberine and evodiamine on metabolic diseases and gut microbiota dysbiosis. However, it is not known whether the combination of berberine and evodiamine (BE) can prevent the development of high-fat diet (HFD)-induced NAFLD. Therefore, we aimed to explore the protective effects of BE on the development of HFD-induced NAFLD from the perspective of the gut microbiota. Gut microbiota profiles were established by high throughput sequencing of the bacterial 16S ribosomal RNA gene. The effects of BE on liver and intestinal tissue, intestinal barrier integrity, and hepatic inflammation were also investigated. The results showed that the abundance and diversity of gut microbiota were enriched by BE treatment, with an increase in beneficial bacteria, such as Lactobacillus, Ruminococcus, and Prevotella, and a decrease in pathogenic bacteria such as Fusobacterium and Lachnospira. In addition, BE effectively improved liver fat accumulation and tissue damage, inhibited the apoptosis of intestinal epithelial cells, increased the contents of intestinal tight junction proteins, and decreased the expression of pro-inflammatory factors. Consequently, BE treatment could be an effective and alternative strategy for alleviating NAFLD by modulating gut microbiota and safeguarding the intestinal barrier.

Relationship between intestinal flora and intestinal barrier dysfunction in patients with sepsis / 中华急诊医学杂志

Objective:To explore the relationship between intestinal flora disorder and intestinal barrier dysfunction in patients with sepsis.Methods:A prospective observational study was conducted to include 10 patients with sepsis (sepsis group) admitted to the ICU of General Hospital of Ningxia Medical University from February 2017 to June 2017, 10 normal postoperative patients (non-sepsis group) admitted to the ICU of General Hospital of Ningxia Medical University in the same period, and 10 healthy persons (control group) were served as controls. General information was recorded. Fecal samples of the three groups of experimental subjects were detected and analyzed by using 16S rRNA gene sequencing technology. The venous blood of the sepsis and non-sepsis groups were collected and the levels of D-lactic acid and bacterial endotoxin in were measured by enzymatic method at the corresponding time points. The correlation between the levels of D-lactic acid and bacterial endotoxin and intestinal flora of patients with sepsis was analyzed.Results:The change consistency of pathogenic bacteria between clinical infection and intestinal pathogenic bacteria in patients with sepsis was observed and analyzed. Sputum culture of patients with sepsis was Acinetobacter baumannii (corresponding patient number: S5, S6, S8), Stenotrophomonas maltophilia (corresponding patient number: S6, S7), and Enterococcus (corresponding patient number: S7). In the intestinal flora of corresponding patients, the OUT abundance were increased. Patients with sepsis (corresponding patient number S7) showed E. coli in blood culture, and in his intestinal flora the OUT abundance was increased. Correlation analysis showed that the serum D-lactic acid level was negatively correlated with the proportion of Firmicutes in intestinal flora in the non-sepsis and sepsis groups, while was positively correlated with the proportion of Firmicutes (r value: -0.532, 0.468, respectively, P<0.05). Conclusions:The gut microbiota dysbiosis is correlated with intestinal barrier function in sepsis patients with sepsis. The spread of pathogenic bacteria between clinical infection and intestinal bacteria in sepsis patients has potential consistency.

Effect of Huazhuo Jiedu Huoxue Tongluo Prescription on Brain-gut Axis of Rats with Cerebral Ischemia-reperfusion Injury Based on 16S rRNA Sequencing of Intestinal Flora / 中国实验方剂学杂志

ObjectiveTo study the effect of Huazhuo Jiedu Huoxue Tongluo （HJHT） prescription on the intestinal flora in rats with cerebral ischemia-reperfusion injury， and to explore the mechanism of Chinese medicinal prescription regulating intestinal flora to restore the balance of brain-gut axis. MethodFifty male SPF SD rats were randomly assigned into sham group， model group， high-dose HJHT group （25.0 g·kg-1）， medium-dose HJHT group （12.5 g·kg-1）， and low-dose HJHT group （6.25 g·kg-1）， with 10 rats in each group. The rat model of permanent middle cerebral artery infarction was established according to Longa method and previous research experience， and reperfusion was performed 2 h after ischemia. The recovery of neurological function deficit and the percentage of cerebral infarction area were detected 72 h after administration. Real-time PCR was performed to detect the mRNA levels of Occludin and zonula occludens-1 （ZO-1） in rat colon. Hematoxylin-eosin （HE） staining was conducted to reveal the intestinal damage. The feces of 6 rats in each group were collected for 16S rRNA sequencing. The expression of Treg and Th17 in intestinal tissue， peripheral blood， and brain tissue were detected. ResultCompared with the sham group， the model group showed obvious neurological deficit （P<0.05） and large cerebral infarction area （P<0.05）. High-dose and medium-doses HJHT alleviated the symptoms of neurological impairment （P<0.05） and reduce the cerebral infarction area （P<0.05） compared with the model group. Compared with the sham group， the model group showed destroyed structure of colonic mucosa and incomplete epithelial cells and goblet cells， while high-dose and medium-doses HJHT alleviated such changes. The mRNA levels of Occludin and ZO-1 in the model group were lower than those in the sham group （P<0.05），and the high-dose HJHT groups were higher than the model group （P<0.05）. The intestinal flora structure was significantly different between the model group and the sham group while similar between the high-dose HJHT group and sham group. Compared with the sham group， the model group showed down-regulated expression of Treg and up-regulated expression of Th17 in the intestinal tissue， peripheral blood， and brain tissue， and high-dose and medium-dose HJHT alleviated the changes in the expression of Treg and Th17 in the model group （P<0.05）. ConclusionHuazhuo Jiedu Huoxue Tongluo prescription may improve the permeability of intestinal wall by adjusting the abundance and diversity of intestinal microorganisms to reduce the migration of intestinal Th17 cells toward the ischemic lateral brain tissue， mitigate the inflammatory response， and thus alleviate the cerebral ischemia-reperfusion injury in rats.

The role of STAT3 in inflammatory bowel disease and colitis-associated cancer and research progress of the related drugs / 药学学报

Signal transducer and activator of transcription (STAT) 3 is a critical transcription factor for cell proliferation and survival. It is activated within cells by many cytokines to mediate immune and inflammatory responses to injury. Inflammatory bowel disease (IBD), represented by Crohn′s disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disease of the intestinal tract. STAT3 has been shown to be abnormally activated in IBD colon tissues by many pro-inflammatory cytokines, leading to disruption of the intestinal mucosal barrier and excessive innate immune and Th17 responses. The persistent chronic inflammation eventually leads to intestinal fibrosis and stenosis. In addition to immune responses, STAT3 is also involved in intestinal fibrosis in IBD by promoting the transcription of fibrosis-related genes. Colitis-associated cancer (CAC) is a particularly aggressive subtype of colorectal cancer and is associated with chronic inflammation-induced IBD. STAT3 has also been associated with CAC initiation and development. STAT3 is overactivated in tumors, which leads to suppression of the anti-tumor activity of immune cells and promotion of cancer cell proliferation, tumor angiogenesis, invasion, and migration. In the present article, we summarize the role of STAT3 in IBD and CAC and the research progress of the related drugs developed for UC and CAC treatment.