Predicting short-term major postoperative complications in intestinal resection for Crohn’s disease:A machine learning-based study

BACKGROUND Due to the complexity and numerous comorbidities associated with Crohn’s disease(CD),the incidence of postoperative complications is high,significantly impacting the recovery and prognosis of patients.Consequently,additional stu-dies are required to precisely predict short-term major complications following intestinal resection(IR),aiding surgical decision-making and optimizing patient care.AIM To construct novel models based on machine learning(ML)to predict short-term major postoperative complications in patients with CD following IR.METHODS A retrospective analysis was performed on clinical data derived from a patient cohort that underwent IR for CD from January 2017 to December 2022.The study participants were randomly allocated to either a training cohort or a validation cohort.The logistic regression and random forest(RF)were applied to construct models in the training cohort,with model discrimination evaluated using the area under the curves(AUC).The validation cohort assessed the performance of the constructed models.RESULTS Out of the 259 patients encompassed in the study,5.0%encountered major postoperative complications(Clavien-Dindo≥III)within 30 d following IR for CD.The AUC for the logistic model was 0.916,significantly lower than the AUC of 0.965 for the RF model.The logistic model incorporated a preoperative CD activity index(CDAI)of≥220,a diminished preoperative serum albumin level,conversion to laparotomy surgery,and an extended operation time.A nomogram for the logistic model was plotted.Except for the surgical approach,the other three variables ranked among the top four important variables in the novel ML model.CONCLUSION Both the nomogram and RF exhibited good performance in predicting short-term major postoperative complic-ations in patients with CD,with the RF model showing more superiority.A preoperative CDAI of≥220,a di-minished preoperative serum albumin level,and an extended operation time might be the most crucial variables.The findings of this study can assist clinicians in identifying patients at a higher risk for complications and offering personalized perioperative management to enhance patient outcomes.

Dietary supplementation of benzoic acid and essential oils combination enhances intestinal resilience against LPS stimulation in weaned piglets

Background The benefits of combining benzoic acid and essential oils(BAO)to mitigate intestinal impairment during the weaning process have been well established,while the detailed underlying mechanism has not been fully elucidated.Previous research has primarily focused on the reparative effects of BAO on intestinal injury,while neglecting its potential in enhancing intestinal stress resistance.Methods In this study,we investigated the pre-protective effect of BAO against LPS-induced stress using a modified experimental procedure.Piglets were pre-supplemented with BAO for 14 d,followed by a challenge with LPS or saline to collect blood and intestinal samples.Results Our findings demonstrated that BAO supplementation led to significant improvements in piglets’final weight,average daily gain,and feed intake/body gain ratio.Additionally,BAO supplementation positively influenced the composition of intestinal microbiota,increasing beneficial Actinobacteriota and Alloprevotella while reducing harmful Desulfobacterota,Prevotella and Oscillospira.Furthermore,BAO supplementation effectively mitigated oxidative disturbances and inflammatory responses induced by acute LPS challenge.This was evidenced by elevated levels of T-AOC,SOD,and GSH,as well as decreased levels of MDA,TNF-α,and IL-6 in the plasma.Moreover,piglets subjected to LPS challenge and pre-supplemented with BAO exhibited significant improvements in intestinal morphological structure and enhanced integrity,as indicated by restored expression levels of Occludin and Claudin-1 compared to the non-supplemented counterparts.Further analysis revealed that BAO supplementation enhanced the jejunal antioxidative capacity by increasing GSH-Px levels and decreasing MDA levels under the LPS challenge and stimulated the activation of the Nrf2 signaling pathway.Additionally,the reduction of TLR4/NF-κB/MAPK signaling pathways activation and proinflammatory factor were also observed in the jejunal of those piglets fed with BAO.Conclusions In summary,our study demonstrates that pre-supplementation of BAO enhances the anti-stress capacity of weaned piglets by improving intestinal microbiota composition,reinforcing the intestinal barrier,and enhancing antioxidative and anti-inflammatory capabilities.These effects are closely associated with the activation of Nrf2 and TLR4/NF-κB/MAPK signaling pathways.

Intestinal glucagon-like peptide-1:A new player associated with impaired counterregulatory responses to hypoglycaemia in type 1 diabetic mice

BACKGROUND Impaired hypoglycaemic counterregulation has emerged as a critical concern for diabetic patients who may be hesitant to medically lower their blood glucose levels due to the fear of potential hypoglycaemic reactions.However,the pathogenesis of hypoglycaemic counterregulation is still unclear.Glucagon-like peptide-1(GLP-1)and its analogues have been used as adjunctive therapies for type 1 diabetes mellitus(T1DM).The role of GLP-1 in counterregulatory dysfunction during hypoglycaemia in patients with T1DM has not been reported.AIM To explore the impact of intestinal GLP-1 on impaired hypoglycaemic counterregulation in type 1 diabetic mice.METHODS T1DM was induced in C57BL/6J mice using streptozotocin,followed by intraperitoneal insulin injections to create T1DM models with either a single episode of hypoglycaemia or recurrent episodes of hypoglycaemia(DH5).Immunofluorescence,Western blot,and enzyme-linked immunosorbent assay were employed to evaluate the influence of intestinal GLP-1 on the sympathetic-adrenal reflex and glucagon(GCG)secretion.The GLP-1 receptor agonist GLP-1(7-36)or the antagonist exendin(9-39)were infused into the terminal ileum or injected intraperitoneally to further investigate the role of intestinal GLP-1 in hypoglycaemic counterregulation in the model mice.RESULTS The expression levels of intestinal GLP-1 and its receptor(GLP-1R)were significantly increased in DH5 mice.Consecutive instances of excess of intestinal GLP-1 weakens the sympathetic-adrenal reflex,leading to dysfunction of adrenal counterregulation during hypoglycaemia.DH5 mice showed increased pancreaticδ-cell mass,cAMP levels inδcells,and plasma somatostatin concentrations,while cAMP levels in pancreaticαcells and plasma GCG levels decreased.Furthermore,GLP-1R expression in islet cells and plasma active GLP-1 levels were significantly increased in the DH5 group.Further experiments involving terminal ileal infusion and intraperitoneal injection in the model mice demonstrated that intestinal GLP-1 during recurrent hypoglycaemia hindered the secretion of the counterregulatory hormone GCG via the endocrine pathway.CONCLUSION Excessive intestinal GLP-1 is strongly associated with impaired counterregulatory responses to hypoglycaemia,leading to reduced appetite and compromised secretion of adrenaline,noradrenaline,and GCG during hypoglycaemia.

Responses of growth performance,antioxidant function,small intestinal morphology and mRNA expression of jejunal tight junction protein to dietary iron in yellow-feathered broilers

This study aimed to investigate the dose-effect of iron on growth performance,antioxidant function.intestinal morphology,and mRNA expression of jejunal tight junction protein in 1-to21-d-old yellow-feathered broilers.A total of 7201-d-old yellow-feathered maleb roilers were allocated to 9 treatments with 8 replicate cages of 10 birds per cage.The dietary treatments were consisted of a basal diet(contained 79.6 mg Fe kg^(-1))supplemented with 0,20,40,60,80,160,320,640,and 1,280 mg Fe kg^(-1)in the form of FeSO_(4)·7H_(2)O.Compared with the birds in the control group,birds supplemented with 20mg Fe kg^(-1)had higher average daily gain(ADG)(P<0.0001).Adding 640 and 1,280 mg Fe kg^(-1)significantly decreased ADG(P<0.0001)and average daily feed intake(ADFI)(P<0.0001)compared with supplementation of 20mg Fe kg^(-1).Malondialdehyde(MDA)concentration in plasma and duodenum increased linearly(P<0.0001),but MDA concentration in liver and jejunum increased linearly(P<0.05)or quadratically(P<0.05)with increased dietary Fe concentration.The villus height(VH)in duodenum and jejunum,and the ratio of villus height to crypt depth(V/C)in duodenum decreased linearly(P?0.05)as dietary Feincreased.As dietary Fe increased,the jejunal relative mRNA abundance of claudin-1 decreased linearly(P=0.001),but the jejunal relative mRNA abundance of zona occludens-1(ZO-1)and occludin decreased linearly(P?0.05)or quadratically(P?0.05).Compared with the supplementation of 20 mg Fe kg^(-1),the supplementation of640 mg Fe kg^(-1)or higher increased(P?0.05)MDA concentrations in plasma,duodenum,and jejunum,decreased VH in the duodenum and jejunum,and the addition of 1,280 mg Fe kg^(-1)reduced(P?0.05)the jejunal tight junction protein(claudin-1,ZO-1,occludin)mRNA abundance.In summary,640 mg of supplemental Fe kg^(-1)or greater was associated with decreased growth performance,increased oxidative stress,disrupted intestinal morphology,and reduced mRNA expression of jejunal tight junction protein.

Experience of primary intestinal lymphangiectasia in adults: Twelve case series from a tertiary referral hospital

BACKGROUND While primary intestinal lymphangiectasia(PIL)is considered a rare condition,there have been several reported cases in adults.Nevertheless,the absence of clear guidance from diagnosis to treatment and prognosis poses challenges for both physicians and patients.AIM To enhance understanding by investigating clinical presentation,diagnosis,treatment,complications,and prognoses in adult PIL cases.METHODS We enrolled adult patients diagnosed with PIL between March 2016 and September 2021.The primary outcome involved examining the diagnosis and treatment process of these patients.The secondary outcomes included identifying complications(infections,thromboembolism)and assessing prognoses(frequency of hospitalization and mortality)during the follow-up period.RESULTS Among the 12 included patients,peripheral edema(100%)and diarrhea(75%)were the main presenting complaints.Laboratory tests showed that all the pati-ents exhibited symptoms of hypoalbuminemia and hypogammaglobulinemia.Radiologically,the predominant findings were edema of the small intestine(67%)and ascites(58%).The typical endoscopic finding with a snowflake appearance was observed in 75%of patients.Among the 12 patients,two responded positive-ly to octreotide and sirolimus,and eight who could undergo maintenance therapy discontinued subsequently.Complications due to PIL led to infection in half of the patients,thromboembolism in three patients,and one death.CONCLUSION PIL can be diagnosed in adults across various age groups,with different severity and treatment responses among patients,leading to diverse complications and prognoses.Consequently,tailored treatments will be necessary.We anticipate that our findings will contribute to the management of PIL,an etiology of protein-losing enteropathy.

Short- and long-term outcomes of surgical treatment in patients with intestinal Behcet’s disease

BACKGROUND Behcet’s disease(BD),a chronic vasculitic disorder affecting multiple organs,is characterized by recurrent oral and genital ulcers,arthritis,vasculitis,and intes-tinal ulcers.Although intestinal involvement of BD is common in East Asia,the efficacy and long-term outcomes of surgical treatment of intestinal BD still remain to be established.AIM To evaluate the postoperative clinical course of intestinal BD and determine factors associated with its recurrence.METHODS Data from patients who underwent surgical treatment for intestinal BD between January 2010 and August 2021 were retrospectively reviewed.Patients’demo-graphics,clinical features,postoperative course,complications,and follow-up data were evaluated.RESULTS We analyzed 39 surgeries in 31 patients.The mean patient age was 45.1 years,and the mean interval between the diagnosis of intestinal BD and surgical treatment was 4.9 years(range 1.0-8.0 years).The most common indication for surgery was medical intractability(n=16,41.0%),followed by fistula or abscess(n=11,28.2%).Laparoscopic approaches were used in 19 patients(48.7%),and 5 patients(12.8%)underwent emergency surgeries.The most common surgical procedure was ileocecal resection(n=18,46.2%),followed by right colectomy(n=11,28.2%).A diverting stoma was created in only one patient(2.6%).During a mean follow-up period of 45(range 8-72)months,eight cases(20.5%)of recurrence in five patients required reoperation.The interval between operations was 12.1 months(range 6.3-17.8 mo).Four patients(10.3%)experienced recurrence within 1 year postoperatively,and all eight recurrences occurred within 2 years of the initial surgery.The reoperation rates at 1 and 3 years were 10.3%and 20.5%,respectively.A redo ileocolic anastomosis was performed in all recurrent cases.In multivariate Cox regression analysis,emergency surgery[hazard ratio(HR)9.357,95%confidence interval(CI):1.608-54.453,P=0.013]and elevated C-reactive protein(CRP)levels(HR 1.154,95%CI:1.002–1.328,P=0.047),but not medication use,were predictors of recurrence.CONCLUSION Surgical resection is a feasible treatment option for complicated BD.Reoperation is associated with severe inflam-matory conditions,reflected by increased CRP levels and the requirement for emergency surgery.

Characterization of mulberry leaf instant tea and evaluation of its hypolipidemia effect via regulation of intestinal microbiota

The purpose of this study was to characterize mulberry leaf instant tea(MLIT)powder prepared from the'Longsang No.1'(Morus abla L.cv.Longsang 1)mulberry leaves in Heilongjiang Province(China)and assess its obesity-preventing/relieving effects.A total of 174 compounds including quercetin,chlorogenic acid,1-deoxyecomycin(1-DNJ)related to antihyperlipidemia effects were identified from the MLIT powder.MLIT treatment reversed the Lee's index,fat coefficient,and serum biochemical parameters in both the obesity relieving and obesity preventing mice fed with high-fat diet.In the obesity relieving experiment,the relative abundance of Desulfovibrio in mouse feces decreased after both 0.5%and 1%MLIT treatments.In obesity preventing experiments,mouse with different amount of MLIT treatments showed increased relative abundance of Akkermansia,Bifidobacterium and Lactobacillus,while Deferribacteres,Desulfobacterota decreased.The beneficial bacteria in the intestinal tract of mice treated with MLIT increased.This study proved that MLIT had antihyperlipidemia potential via modulating intestinal microbiota in mice.

Clinical diagnostic advances in intestinal anastomotic techniques:Hand suturing,stapling,and compression devices

The development of intestinal anastomosis techniques,including hand suturing,stapling,and compression anastomoses,has been a significant advancement in surgical practice.These methods aim to prevent leakage and minimize tissue fibrosis,which can lead to stricture formation.The healing process involves various phases:hemostasis and inflammation,proliferation,and remodeling.Mechanical staplers and sutures can cause inflammation and fibrosis due to the release of profibrotic chemokines.Compression anastomosis devices,including those made of nickel-titanium alloy,offer a minimally invasive option for various surgical challenges and have shown safety and efficacy.However,despite advancements,anastomotic techniques are evaluated based on leakage risk,with complications being a primary concern.Newer devices like Magnamosis use magnetic rings for compression anastomosis,demonstrating greater strength and patency compared to stapling.Magnetic technology is also being explored for other medical treatments.While there are promising results,particularly in animal models,the realworld application in humans is limited,and further research is needed to assess their safety and practicality.

Geroprotection from ergothioneine treatment in Drosophila melanogaster by improving intestinal barrier and activation of intestinal autophagy

Ergothioneine is a natural amino acid with powerful antioxidant activity.Previous studies have demonstrated that ergothioneine can increase the lifespan of Drosophila melanogaster and Caenorhabditis elegans,and enhance telomerase activity.In present study,the metagenomics sequencing and quantitative real-time polymerase chain reaction analysis were employed to characterize the composition and diversity of gut microbiome in aging flies.And the alterations in the gut barrier,gut morphology,and other gut physiological indicators of aging flies were evaluated.Here,the results showed that ergothioneine induced little variations in gut microbiota composition in flies at mid-life,and significant alterations in the gut microbiota populations were only observed in flies at late-life.And ergothioneine attenuated age-related gut injuries,including decreasing reactive oxygen species levels in intestinal enterocytes,reduction of intestinal cells death,and preservation of gut integrity in aging flies.Ergothioneine also improved the gut morphology by preserving the structure and shape of cell organelles and inducing the intestinal autophagy.And activation of intestinal autophagy also contributed to the longevity effect mediated by ergothioneine in an unidentified mechanism.

Qualitative exploration of home life experiences and care needs among elderly patients with temporary intestinal stomas

BACKGROUND This study employed a phenomenological research approach within qualitative research to explore the challenges encountered by elderly individuals with temporary colostomies in managing their daily lives and care needs.Protecting the anus surgery combined with temporary colostomy has emerged as a prevalent treatment modality for low rectal cancer.However,the ileostomy is susceptible to peri-stoma skin complications,as well as fluid,electrolyte,and nutritional imbalances,posing challenges to effective management.The successful selfmanagement of patients is intricately linked to their adjustment to temporary colostomy;nonetheless,there remains a dearth of research examining the factors influencing self-care among temporary colostomy patients and the obstacles they confront.AIM To investigate the lived experiences,perceptions,and care requirements of temporary colostomy patients within their home environment,with the ultimate goal of formulating a standardized management protocol.METHODS Over the period of June to August 2023,a purposive sampling technique was utilized to select 12 patients with temporary intestinal stomas from a tertiary hospital in Shanghai,China.Employing a phenomenological research approach,a semi-structured interview guide was developed,and qualitative interviews were conducted using in-depth interview techniques.The acquired data underwent coding,analysis,organization,and summarization following Colaizzi’s seven-step method.RESULTS The findings of this study revealed that the experiences and needs of patients with temporary intestinal stomas can be delineated into four principal themes:Firstly,Temporary colostomy patients bear various burdens and concerns about the uncertainty of disease progression;secondly,patients exhibit limited self-care capabilities and face information deficits,resulting in heightened reliance on healthcare professionals;thirdly,patients demonstrate the potential for internal motivation through proactive self-adjustment;and finally,patients express a significant need for emotional and social support.CONCLUSION Home-living patients with temporary intestinal stomas confront multifaceted challenges encompassing burdens,inadequate self-care abilities,informational deficits,and emotional needs.Identifying factors influencing patients’self-care at home and proposing strategies to mitigate barriers can serve as a foundational framework for developing and implementing nursing interventions tailored to the needs of patients with temporary intestinal stomas.

Correlation between Intestinal Health and Coccidiosis Prevalence in Broilers during Different Seasons of the Year in Brazil from 2012 to 2018

Coccidiosis is a disease caused by intracellular protozoan parasites, specifically belonging to the genus Eimeria. These parasites target the gastrointestinal tract in different types of hosts, causing sores in the intestinal lining. The presence of these lesions reduces the animal’s ability to digest and absorb nutrients, significantly impacting their overall performance. The current study aimed to explore the potential correlation between seasonal variations and the incidence of Eimeria spp-induced lesions in broiler chickens’ gastrointestinal tracts in Brazil from 2012 to 2018. A total of 8,607 broiler chickens, aged 14 to 42 days, were sampled from 103 poultry integrated companies in Brazil to conduct intestinal health examinations. The sampling process involved selecting 3 to 6 chickens from each poultry house for examination. The assessment included various abnormalities such as shedding of intestinal cells and excessive fluid and mucus presence, thickening and tension of the intestines, food movement, roughened mucosal surface resembling a Turkish towel in the small intestine, tissue death, duodenal inflammation, intestinal inflammation, gizzard erosion, presence of worms and bedding material, and ingestion of mealworms. During the seasons, winter exhibited the highest average occurrence of Eimeria maxima microorganisms at 52.83%, with E. acervulina following closely at 26.42% in second place. In spring, E. maxima had an occurrence of 11.31%, while in fall, E. tenella had the lowest occurrence at 6.74%. When analyzing the seasonal occurrence of Eimeria, it was observed that E. maxima micro was more common during winter compared to summer (P = 0.0491). However, no discernible variation was observed in the occurrence of the remaining species across different seasons. Research findings suggest that subclinical coccidiosis is most prevalent during the winter season in Brazil. Likewise, clinical disease caused by E. acervulina is also prevalent during this time. In contrast, E. maxima is more likely to cause clinical disease in the spring, whereas E. tenella is more commonly associated with clinical disease in the fall. Lesions induced by Eimeria spp. are associated with factors influencing the overall health of broiler intestines. These findings allow for the utilization of seasonal metrics in disease management, thereby reducing economic losses associated with the condition.

Effects of methionine supplementation in a reduced protein diet on growth performance, oxidative status, intestinal health, oocyst shedding, and methionine and folate metabolism in broilers under Eimeria challenge

Background This study investigated effects of different methionine(Met)supplementation levels in a reduced protein diet on growth performance,intestinal health,and different physiological parameters in broilers under Eimeria challenge.A total of 600 fourteen-day-old Cobb500 male broilers were challenged with E.maxima,E.tenella,and E.acervulina,and randomly allocated in a 2×5 factorial arrangement.Birds received normal protein diets(20%crude protein,NCP)or reduced protein diets(17%crude protein,LCP),containing 2.8,4.4,6.0,7.6,and 9.2 g/kg of Met.Results On 6 and 9 days post inoculation(DPI),increasing Met level linearly improved the growth performance(P<0.05).Total oocyst shedding linearly increased as Met level increased(P<0.05).Duodenal villus height(VH):crypt depth(CD)in the LCP groups were higher on 6 DPI(P<0.01)while lower on 9 DPI(P<0.05)compared to the NCP groups.Jejunal CD and duodenal VH:CD changed quadratically as Met level increased(P<0.05).On 6 DPI,liver glutathione(GSH)and glutathione disulfide(GSSG)linearly increased as Met level increased(P<0.05).On 9 DPI,GSSG quadratically increased,whereas GSH:GSSG quadratically decreased as Met levels increased(P<0.05).The expression of amino acid transporters linearly decreased as Met level increased(P<0.05).The expression of zonula occludens 2 and claudin-1 linearly increased on 6 DPI whereas decreased on 9 DPI as Met level increased(P<0.05).The expressions of cytokines were lower in the LCP groups than the NCP groups(P<0.05).Interaction effects were found for the expression of IL-10 and TNFαon 6 DPI(P<0.05),where it only changed quadratically in the NCP group as Met level increased.The expression of Met and folate metabolism genes were lower in the LCP groups than the NCP groups on 9 DPI(P<0.05).The expression of these genes linearly or quadratically decreased as Met level increased(P<0.05).Conclusion These results revealed the regulatory roles of Met in different physiological parameters including oxidative status,intestinal health,and nutrient metabolism in birds fed reduced protein diet and challenged with Eimeria.

Jianpi-Huatan-Huoxue-Anshen formula ameliorates gastrointestinal inflammation and microecological imbalance in chemotherapytreated mice transplanted with H22 hepatocellular carcinoma

BACKGROUND Jianpi-Huatan-Huoxue-Anshen formula[Tzu-Chi cancer-antagonizing&lifeprotecting II decoction(TCCL)]is a Chinese medical formula that has been clinically shown to reduce the gastrointestinal side effects of chemotherapy in cancer patients and improve their quality of life.However,its effect and mechanism on the intestinal microecology after chemotherapy are not yet clear.AIM To discover the potential mechanisms of TCCL on gastrointestinal inflammation and microecological imbalance in chemotherapy-treated mice transplanted with hepatocellular carcinoma(HCC).METHODS Ninety-six mice were inoculated subcutaneously with HCC cells.One week later,the mice received a large dose of 5-fluorouracil by intraperitoneal injection to establish a HCC chemotherapy model.Thirty-six mice were randomly selected before administration,and feces,ileal tissue,and ileal contents were collected from each mouse.The remaining mice were randomized into normal saline,continuous chemotherapy,Yangzheng Xiaoji capsulestreated,and three TCCL-treated groups.After treatment,feces,tumors,liver,spleen,thymus,stomach,jejunum,ileum,and colon tissues,and ileal contents were collected.Morphological changes,serum levels of IL-1β,IL-6,IL-8,IL-10,IL-22,TNF-α,and TGF-β,intestinal SIgA,and protein and mRNA expression of ZO-1,NF-κB,Occludin,MUC-2,Claudin-1,and IκB-αin colon tissues were documented.The effect of TCCL on the abundance and diversity of intestinal flora was analyzed using 16S rDNA sequencing.RESULTS TCCL treatment improved thymus and spleen weight,thymus and spleen indexes,and body weight,decreased tumor volumes and tumor tissue cell density,and alleviated injury to gastric,ileal,and colonic mucosal tissues.Among proteins and genes associated with inflammation,IL-10,TGF-β,SIgA,ZO-1,MUC-2,and Occludin were upregulated,whereas NF-κB,IL-1β,IL-6,TNF-α,IL-22,IL-8,and IκB-αwere downregulated.Additionally,TCCL increased the proportions of fecal Actinobacteria,AF12,Adlercreutzia,Clostridium,Coriobacteriaceae,and Paraprevotella in the intermediate stage of treatment,decreased the proportions of Mucipirillum,Odoribacter,RF32,YS2,and Rikenellaceae but increased the proportions of p_Deferribacteres and Lactobacillus at the end of treatment.Studies on ileal mucosal microbiota showed similar findings.Moreover,TCCL improved community richness,evenness,and the diversity of fecal and ileal mucosal flora.CONCLUSION TCCL relieves pathological changes in tumor tissue and chemotherapy-induced gastrointestinal injury,potentially by reducing the release of pro-inflammatory factors to repair the gastrointestinal mucosa,enhancing intestinal barrier function,and maintaining gastrointestinal microecological balance.Hence,TCCL is a very effective adjuvant to chemotherapy.

Dietary supplementation of zinc oxide modulates intestinal functionality during the post-weaning period in clinically healthy piglets

Background To improve our understanding of host and intestinal microbiome interaction,this research investigated the effects of a high-level zinc oxide in the diet as model intervention on the intestinal microbiome and small intestinal functionality in clinically healthy post-weaning piglets.In study 1,piglets received either a high concentration of zinc(Zn)as zinc oxide(Zn O,Zn,2,690 mg/kg)or a low Zn concentration(100 mg/kg)in the diet during the post weaning period(d 14–23).The effects on the piglet's small intestinal microbiome and functionality of intestinal tissue were investigated.In study 2,the impact of timing of the dietary zinc intervention was investigated,i.e.,between d 0–14 and/or d 14–23 post weaning,and the consecutive effects on the piglet's intestinal functionality,here referring to microbiota composition and diversity and gene expression profiles.Results Differences in the small intestinal functionality were observed during the post weaning period between piglets receiving a diet with a low or high concentration Zn O content.A shift in the microbiota composition in the small intestine was observed that could be characterized as a non-pathological change,where mainly the commensals inter-changed.In the immediate post weaning period,i.e.,d 0–14,the highest number of differentially expressed genes(DEGs)in intestinal tissue were observed between animals receiving a diet with a low or high concentration Zn O content,i.e.,23 DEGs in jejunal tissue and 11 DEGs in ileal tissue.These genes are involved in biological processes related to immunity and inflammatory responses.For example,genes CD59 and REG3G were downregulated in the animals receiving a diet with a high concentration Zn O content compared to low Zn O content in both jejunum and ileum tissue.In the second study,a similar result was obtained regarding the expression of genes in intestinal tissue related to immune pathways when comparing piglets receiving a diet with a high concentration Zn O content compared to low Zn O content.Conclusions Supplementing a diet with a pharmaceutical level of Zn as Zn O for clinically healthy post weaning piglets influences various aspects intestinal functionality,in particular in the first two weeks post-weaning.The model intervention increased both the alpha diversity of the intestinal microbiome and the expression of a limited number of genes linked to the local immune system in intestinal tissue.The effects do not seem related to a direct antimicrobial effect of Zn O.

Umbilical cord mesenchymal stem cell exosomes alleviate necrotizing enterocolitis in neonatal mice by regulating intestinal epithelial cells autophagy

BACKGROUND Necrotizing enterocolitis(NEC)is a severe gastrointestinal disease that affects premature infants.Although mounting evidence supports the therapeutic effect of exosomes on NEC,the underlying mechanisms remain unclear.AIM To investigate the mechanisms underlying the regulation of inflammatory response and intestinal barrier function by umbilical cord mesenchymal stem cell(UCMSCs)exosomes,as well as their potential in alleviating NEC in neonatal mice.METHODS NEC was induced in 5-d-old C57BL/6 pups through hypoxia and gavage feeding of formula containing lipopolysaccharide(LPS),after which the mice received human UCMSC exosomes(hUCMSC-exos).The control mice were allowed to breastfeed with their dams.Ileal tissues were collected from the mice and analyzed by histopathology and immunoblotting.Colon tissues were collected from NEC neonates and analyzed by immunofluorescence.Molecular biology and cell culture approaches were employed to study the related mechanisms in intestinal epithelial cells.RESULTS We found that autophagy is overactivated in intestinal epithelial cells during NEC,resulting in reduced expression of tight junction proteins and an increased inflammatory response.The ability of hUCMSC-exos to ameliorate NEC in a mouse model was dependent on decreased intestinal autophagy.We also showed that hUCMSC-exos alleviate the inflammatory response and increase migration ability in intestinal epithelial cells induced by LPS.CONCLUSION These results contribute to a better understanding of the protective mechanisms of hUCMSC-exos against NEC and provide a new theoretical and experimental foundation for NEC treatment.These findings also enhance our understanding of the role of the autophagy mechanism in NEC,offering potential avenues for identifying new therapeutic targets.

RKDG Methods with Multi-resolution WENO Limiters for Solving Steady-State Problems on Triangular Meshes

In this paper, we design high-order Runge-Kutta discontinuous Galerkin (RKDG) methods with multi-resolution weighted essentially non-oscillatory (multi-resolution WENO) limiters to compute compressible steady-state problems on triangular meshes. A troubled cell indicator extended from structured meshes to unstructured meshes is constructed to identify triangular cells in which the application of the limiting procedures is required. In such troubled cells, the multi-resolution WENO limiting methods are used to the hierarchical L^(2) projection polynomial sequence of the DG solution. Through using the RKDG methods with multi-resolution WENO limiters, the optimal high-order accuracy can be gradually reduced to first-order in the triangular troubled cells, so that the shock wave oscillations can be well suppressed. In steady-state simulations on triangular meshes, the numerical residual converges to near machine zero. The proposed spatial reconstruction methods enhance the robustness of classical DG methods on triangular meshes. The good results of these RKDG methods with multi-resolution WENO limiters are verified by a series of two-dimensional steady-state problems.

Dietary eubiotics of microbial muramidase and glycan improve intestinal villi,ileum microbiota composition and production trait of broiler

Background Optimal gut health is important to maximize growth performance and feed efficiency in broiler chickens.A total of 1,365 one-day-old male Ross 308 broiler chickens were randomly divided into 5 treatments groups with 21 replicates,13 birds per replicate.The present research investigated effects of microbial muramidase or a precision glycan alone or in combination on growth performance,apparent total tract digestibility,total blood carotenoid content,intestinal villus length,meat quality and gut microbiota in broiler chickens.Treatments included:NC:negative control(basal diet group);PC:positive control(basal diet+0.02%probiotics);MR:basal diet+0.035%microbial muramidase;PG:basal diet+0.1%precision glycan;and MRPG:basal diet+0.025%MR+0.1%PG,respectively.Results MRPG group increased the body weight gain and feed intake(P<0.05)compared with NC group.Moreover,it significantly increased total serum carotenoid(P<0.05)and MRPG altered the microbial diversity in ileum contents.The MRPG treatment group increased the abundance of the phylum Firmicutes,and family Lachnospiraceae,Ruminococcaceae,Oscillospiraceae,Lactobacillaceae,Peptostreptococcaceae and decreased the abundance of the phylum Campilobacterota,Bacteroidota and family Bacteroidaceae.Compared with the NC group,the chickens fed MRPG showed significantly increased in duodenum villus length at end the trial.Conclusion In this study,overall results showed that the synergetic effects of MR and PG showed enhancing growth performance,total serum carotenoid level and altering gut microbiota composition of broilers.The current research indicates that co-supplementation of MR and PG in broiler diets enhances intestinal health,consequently leading to an increased broiler production.

27-Hydroxycholesterol/liver X receptor/apolipoprotein E mediates zearalenone-induced intestinal immunosuppression:A key target potentially linking zearalenone and cancer

Zearalenone(ZEN)is a mycotoxin that extensively contaminates food and feed,posing a significant threat to public health.However,the mechanisms behind ZEN-induced intestinal immunotoxicity remain unclear.In this study,Sprague-Dawley(SD)rats were exposed to ZEN at a dosage of 5 mg/kg/day b.w.for a duration of 14 days.The results demonstrated that ZEN exposure led to notable pathological alterations and immunosuppression within the intestine.Furthermore,ZEN exposure caused a significant reduction in the levels of apolipoprotein E(ApoE)and liver X receptor(LXR)(P<0.05).Conversely,it upregulated the levels of myeloid-derived suppressor cells(MDSCs)markers(P<0.05)and decreased the presence of 27-hydroxycholesterol(27-HC)in the intestine(P<0.05).It was observed that ApoE or LXR agonists were able to mitigate the immunosuppressive effects induced by ZEN.Additionally,a bioinformatics analysis highlighted that the downregulation of ApoE might elevate the susceptibility to colorectal,breast,and lung cancers.These findings underscore the crucial role of the 27-HC/LXR/ApoE axis disruption in ZEN-induced MDSCs proliferation and subsequent inhibition of T lymphocyte activation within the rat intestine.Notably,ApoE may emerge as a pivotal target linking ZEN exposure to cancer development.

Gastrointestinal problems in a valproic acid-induced rat model of autism: From maternal intestinal health to offspring intestinal function

BACKGROUND Autism spectrum disorder(ASD)is a developmental disorder characterized by social deficits and repetitive behavior.Gastrointestinal(GI)problems,such as constipation,diarrhea,and inflammatory bowel disease,commonly occur in patients with ASD.Previously,GI problems of ASD patients were attributed to intestinal inflammation and vertical mother-to-infant microbiome transmission.AIM To explore whether GI problems in ASD are related to maternal intestinal inflam-mation and gut microbiota abnormalities.METHODS An ASD rat model was developed using valproic acid(VPA).Enzyme-linked immunosorbent assay and fecal 16S rRNA sequencing were used to test GI changes.RESULTS VPA exposure during pregnancy led to pathological maternal intestinal changes,resulting in alterations in maternal gut microbiota.Additionally,the levels of inflammatory factors also increased.Moreover,prenatal exposure to VPA resulted in impaired duodenal motility in the offspring as well as increased levels of infla-mmatory factors.CONCLUSION GI problems in ASD may be associated with maternal intestinal inflammation and microbiota abnormality.Future research is required to find more evidence on the etiology and treatment of GI problems in ASD.

Investigation of the nutritional and functional roles of a combinational use of xylanase and β-glucanase on intestinal health and growth of nursery pigs

Background Xylanase andβ-glucanase combination(XG)hydrolyzes soluble non-starch polysaccharides that are anti-nutritional compounds.This study aimed to evaluate the effects of increasing levels of XG on intestinal health and growth performance of nursery pigs.Methods Forty pigs(6.5±0.4 kg)were assigned to 5 dietary treatments and fed for 35 d in 3 phases(11,9,and 15 d,respectively).Basal diets mainly included corn,soybean meal,and corn distiller's dried grains with solubles,contained phytase(750 FTU/kg),and were supplemented with 5 levels of XG at(1)0,(2)280 TXU/kg xylanase and 125 TGU/kgβ-glucanase,(3)560 and 250,(4)840 and 375,or(5)1,120 and 500,respectively.Growth performance was measured.On d 35,all pigs were euthanized and jejunal mucosa,jejunal digesta,jejunal tissues,and ileal digesta were collected to determine the effects of increasing XG levels and XG intake on intestinal health.Results Increasing XG intake tended to quadratically decrease(P=0.059)viscosity of jejunal digesta(min:1.74 m Pa·s at 751/335(TXU/TGU)/kg).Increasing levels of XG quadratically decreased(P<0.05)Prevotellaceae(min:0.6%at 630/281(TXU/TGU)/kg)in the jejunal mucosa.Increasing XG intake quadratically increased(P<0.05)Lactobacillaceae(max:40.3%at 608/271(TXU/TGU)/kg)in the jejunal mucosa.Increasing XG intake quadratically decreased(P<0.05)Helicobacteraceae(min:1.6%at 560/250(TXU/TGU)/kg)in the jejunal mucosa.Increasing levels of XG tended to linearly decrease(P=0.073)jejunal Ig G and tended to quadratically increase(P=0.085)jejunal villus height to crypt depth ratio(max:2.62 at 560/250(TXU/TGU)/kg).Increasing XG intake tended to linearly increase the apparent ileal digestibility of dry matter(P=0.087)and ether extract(P=0.065).Increasing XG intake linearly increased(P<0.05)average daily gain.Conclusions A combinational use of xylanase andβ-glucanase would hydrolyze the non-starch polysaccharides fractions,positively modulating the jejunal mucosa-associated microbiota.Increased intake of these enzyme combination possibly reduced digesta viscosity and humoral immune response in the jejunum resulting in improved intestinal structure,and ileal digestibility of nutrients,and finally improving growth of nursery pigs.The beneficial effects were maximized at a combination of 550 to 800 TXU/kg xylanase and 250 to 360 TGU/kgβ-glucanase.