Melt electrowriting-printed peritoneal scaffold prevents peritoneal adhesion and facilitates peritoneal repair.

Peritoneal adhesion is a critical issue after abdominal surgery. Cell-based methods for preventing peritoneal adhesion have not yet been fully investigated. Here, we constructed a highly biomimetic peritoneal scaffold by seeding mesothelial cells, the natural physiological barrier of the peritoneum, onto a melt electrowriting-printed scaffold. The scaffolds with the microfibers crossed at different angles (30°, 60°, and 90°) were screened based on mesothelial cell proliferation and orientation. Thirty degrees were more suitable for improving proliferation of mesothelial cells and cell growth in a single direction; therefore, the 30° peritoneal scaffold could better mimic the physiological structure of native peritoneum. Mechanistically, such a peritoneal scaffold was able to act as a barrier to prevent peritoneal resident macrophages from migrating to the site of the peritoneal lesion. In vivo mesothelial cell tracking using lentivirus technology confirmed that the peritoneal scaffold, compared to the scaffold without mesothelial cells, could prevent peritoneal adhesion and was directly involved in the repair of injured peritoneum. This study suggests that the peritoneal scaffolds can potentially prevent peritoneal adhesion, offering a new approach for clinical treatment.

Whole Model Path Planning-Guided Multi-Axis and Multi-Material Printing of High-Performance Intestinal Implantable Stent.

The problems of step effects, supporting material waste, and conflict between flexibility and toughness for 3D printed intestinal fistula stents are not yet resolved. Herein, the fabrication of a support-free segmental stent with two types of thermoplastic polyurethane (TPU) using a homemade multi-axis and multi-material conformal printer guided with advanced whole model path planning is demonstrated. One type of TPU segment is soft to increase elasticity, and the other is used to achieve toughness. Owing to advancements in stent design and printing, the obtained stents present three unprecedented properties compared to previous three-axis printed stents: i) Overcoming step effects; ii) Presenting comparable axial flexibility to a stent made of a single soft TPU 87A material, thus increasing the feasibility of implantation; and iii) Showing equivalent radial toughness to a stent made of a single hard TPU 95A material. Hence, the stent can resist the intestinal contractive force and maintain intestinal continuity and patency. Through implanting such stents to the rabbit intestinal fistula models, therapeutic mechanisms of reducing fistula output and improving nutritional states and intestinal flora abundance are revealed. Overall, this study develops a creative and versatile method to improve the poor quality and mechanical properties of medical stents.

Subphenotyping heterogeneous patients with chronic critical illness to guide individualised fluid balance treatment using machine learning: a retrospective cohort study.

Background: The great heterogeneity of patients with chronic critical illness (CCI) leads to difficulty for intensive care unit (ICU) management. Identifying subphenotypes could assist in individualized care, which has not yet been explored. In this study, we aim to identify the subphenotypes of patients with CCI and reveal the heterogeneous treatment effect of fluid balance for them. Methods: In this retrospective study, we defined CCI as an ICU length of stay over 14 days and coexists with persistent organ dysfunction (cardiovascular Sequential Organ Failure Assessment (SOFA) score ≥1 or score in any other organ system ≥2) at Day 14. Data from five electronic healthcare record datasets covering geographically distinct populations (the US, Europe, and China) were studied. These five datasets include (1) subset of Derivation (MIMIC-IV v1.0, US) cohort (2008-2019); (2) subset Derivation (MIMIC-III v1.4 'CareVue', US) cohort (2001-2008); (3) Validation I (eICU-CRD, US) cohort (2014-2015); (4) Validation II (AmsterdamUMCdb/AUMC, Euro) cohort (2003-2016); (5) Validation III (Jinling, CN) cohort (2017-2021). Patients who meet the criteria of CCI in their first ICU admission period were included in this study. Patients with age over 89 or under 18 years old were excluded. Three unsupervised clustering algorithms were employed independently for phenotypes derivation and validation. Extreme Gradient Boosting (XGBoost) was used for phenotype classifier construction. A parametric G-formula model was applied to estimate the cumulative risk under different daily fluid management strategies in different subphenotypes of ICU mortality. Findings: We identified four subphenotypes as Phenotype A, B, C, and D in a total of 8145 patients from three countries. Phenotype A is the mildest and youngest subgroup; Phenotype B is the most common group, of whom patients showed the oldest age, significant acid-base abnormality, and low white blood cell count; Patients with Phenotype C have hypernatremia, hyperchloremia, and hypercatabolic status; and in Phenotype D, patients accompany with the most severe multiple organ failure. An easy-to-use classifier showed good effectiveness. Phenotype characteristics showed robustness across all cohorts. The beneficial fluid balance threshold intervals of subphenotypes were different. Interpretation: We identified four novel phenotypes that revealed the different patterns and significant heterogeneous treatment effects of fluid therapy within patients with CCI. A prospective study is needed to validate our findings, which could inform clinical practice and guide future research on individualized care. Funding: This study was funded by 333 High Level Talents Training Project of Jiangsu Province (BRA2019011), General Program of Medical Research from the Jiangsu Commission of Health (M2020052), and Key Research and Development Program of Jiangsu Province (BE2022823).

Biomimetic Design of Double-Sided Functionalized Silver Nanoparticle/Bacterial Cellulose/Hydroxyapatite Hydrogel Mesh for Temporary Cranioplasty.

A structurally stable and antibacterial biomaterial used for temporary cranioplasty with guided bone regeneration (GBR) effects is an urgent clinical requirement. Herein, we reported the design of a biomimetic Ag/bacterial cellulose/hydroxyapatite (Ag/BC@HAp) hydrogel mesh with a double-sided functionalized structure, in which one layer was dense and covered with Ag nanoparticles and the other layer was porous and anchored with hydroxyapatite (HAp) via mineralization for different durations. Such a double-sided functionalized design endowed the hydrogel with distinguished antibacterial activities for inhibiting potential infections and GBR effects that could prevent endothelial cells and fibroblasts from migrating to a defected area and meanwhile show biocompatibility to MC3T3-E1 preosteoblasts. Furthermore, it was found from in vivo experimental results that the Ag/BC@HAp hydrogel with 7-day mineralization achieved optimal GBR effects by improving barrier functions toward these undesired cells. Moreover, this BC-based hydrogel mesh showed an extremely low swelling ratio and strong mechanical strength, which facilitated the protection of soft brain tissues without gaining the risk of intracranial pressure increase. In a word, this study offers a new approach to double-sided functionalized hydrogels and provides effective and safe biomaterials used for temporary cranioplasty with antibacterial abilities and GBR effects.

Self-Healing Supramolecular Hydrogels with Antibacterial Abilities for Wound Healing.

Wound healing due to skin defects is a growing clinical concern. Especially when infection occurs, it not only leads to impair healing of the wound but even leads to the occurrence of death. In this study, a self-healing supramolecular hydrogel with antibacterial abilities was developed for wound healing. The supramolecular hydrogels inherited excellent self-healing and mechanical properties are produced by the polymerization of N-acryloyl glycinamide monomers which carries a lot of amides. In addition, excellent antibacterial properties are obtained by integrating silver nanoparticles (Ag NPs) into the hydrogels. The resultant hydrogel has a demonstrated ability in superior mechanical properties, including stretchability and self-healing. Also, the good biocompatibility and antibacterial ability have been proven in hydrogels. Besides, the prepared hydrogels were employed as wound dressings to treat skin wounds of animals. It was found that the hydrogels could significantly promote wound repair, including relieving inflammation, promoting collagen deposition, and enhancing angiogenesis. Therefore, such self-healing supramolecular hydrogels with composite functional nanomaterials are expected to be used as new wound dressings in the field of healthcare.

Trocar Puncture With a Sump Drain for Crohn's Disease With Intra-Abdominal Abscess: A 10-Year Retrospective Cohort Study.

Background: Traditional percutaneous catheter drainage (PCD) and surgical intervention could not always achieve satisfactory results for patients with Crohn's disease (CD) who have complications with intra-abdominal abscess. We proposed a trocar puncture with sump drainage for the treatment of CD with intra-abdominal abscess and compared it with the conventional PCD and surgical intervention. Methods: Crohn's disease patients with intra-abdominal abscess and admitted to our hospital from 2011 to 2020 were identified by reviewing the electronic medical records. We divided them into Trocar, PCD, and fecal diverting (FD) groups, according to the ways of treating an abscess. Outcomes, risk factors for abscess recurrence, and postoperative complications were compared among the three groups. Results: A total of 69 patients were included and they were divided into Trocar (n = 18), PCD (n = 29), and FD (n = 22) groups. Four patients in the PCD group were transferred to receive the FD surgery due to the failure of initial treatment. The incidence of abscess recurrence was significantly higher in the PCD (48%) and FD (50%) groups compared to the patients using the trocar puncture with the sump drain (Trocar group) (16.7%). There were 8 patients in Trocar, 22 in PCD, and 20 s in the FD group who received enterectomy. None of the patients in the Trocar had an ultimate stoma and the incidence of postoperative complications was statistically lower [0% (Trocar) vs. 31.8% (PCD) vs. 45% (FD), P < 0.05]. The way of initial treating of the abscess was significantly correlated with the abscess recurrence and postoperative complications. Conclusions: Trocar puncture with a sump drain had a lower incidence of abscess recurrence, abdominal adhesions, postdrainage, and postoperative complications compared to the conventional PCD or surgical intervention.

STING-mediated Syk Signaling Attenuates Tumorigenesis of Colitis­associated Colorectal Cancer Through Enhancing Intestinal Epithelium Pyroptosis.

BACKGROUND: Stimulator of interferon genes (STING) has essential functions in the immune responses and can induce cancer cell apoptosis. However, it is not completely clear how STING plays a role in colitis-associated colorectal cancer (CAC) and whether it can trigger pyroptosis during the tumorigenesis of CAC. METHODS: To investigate the role of STING-modulated pyroptosis in the development of CAC, STING knockout and Wild type mice were challenged with azoxymethane (AOM) and dextran sodium sulfate (DSS) to establish a murine CAC model. STING pharmacological agonist was used to further study the functions of STING signaling in the tumorigenesis. Moreover, STING endogenous ligand was employed to verify the effects of STING in human colon cancer cells. RESULTS: STING deficiency mice were more susceptible to CAC by reducing pyroptosis of tumor cells, whereas overactivation of STING with the agonist suppressed tumorigenesis of CAC. STING also managed CAC development by modulating tumor cells proliferation, adhesion, and invasion, as well as inflammatory response. The ex vivo studies indicated that STING could induce pyroptosis via spleen tyrosine kinase (Syk), and Syk knockdown weakened such pyroptotic tumor cells death. In addition, the visible physical interaction between STING and Syk was observed in colorectal tumor samples of CAC patients. CONCLUSIONS: STING-mediated Syk signaling may regulate the tumorigenesis of CAC by modulating pyroptosis of tumor cells, and modulation of STING/Syk serves as a novel therapeutic strategy for CAC therapy.

Intestinal mucosa-derived DNA methylation signatures in the penetrating intestinal mucosal lesions of Crohn's disease.

The purpose of this study was to evaluate genome-wide DNA methylation changes in intestinal mucosa tissue of adult patients with Crohn's disease comprehensively. DNA methylation chip was used to analyze abnormal methylation sites among penetrating and non-penetrating intestinal mucosa tissue of Crohn's disease and normal intestinal mucosa tissue of healthy controls. Methylation abnormalities of different locus were verified by pyrosequencing and quantitative polymerase chain reaction. Differential DNA methylation sites were participated in the positive regulation of apoptosis and the positive regulation of IL-8 production and were enriched in signaling pathways related to inflammatory bowel disease and extracellular matrix receptor interaction signaling pathways. Correlation analysis showed that the methylation abnormalities of HLA-DRB1 (r = - 0.62, P < 0.001), MUC1 (r = - 0.45, P = 0.01), YPEL5 (r = - 0.55, P = 0.001) and CBLB (r = - 0.62, P < 0.001) were significantly negatively correlated with their relative expression levels. The degree of methylation abnormality of MUC1 was negatively correlated with the disease activity score of Crohn's disease (r = - 0.50, P = 0.01). Apoptosis, interleukin-8 production and abnormal extracellular matrix might be involved in the mechanism of penetrating intestinal mucosal lesions in Crohn's disease. The degree of abnormal methylation of MUC1 was negatively correlated with the disease activity of Crohn's disease.

CCL4-mediated targeting of spleen tyrosine kinase (Syk) inhibitor using nanoparticles alleviates inflammatory bowel disease.

Inflammatory bowel disease (IBD) has emerged a global disease and the ascending incidence and prevalence is accompanied by elevated morbidity, mortality, and substantial healthcare system costs. However, the current typical one-size-fits-all therapeutic approach is suboptimal for a substantial proportion of patients due to the variability in the course of IBD and a considerable number of patients do not have positive response to the clinically approved drugs, so there is still a great, unmet demand for novel alternative therapeutic approaches. Spleen tyrosine kinase (Syk), a cytoplasmic nonreceptor protein tyrosine kinase, plays crucial roles in signal transduction and there are emerging data implicating that Syk participates in pathogenesis of several gut disorders, such as IBD. In this study, we observed the Syk expression in IBD patients and explored the effects of therapeutic Syk inhibition using small-molecule Syk inhibitor piceatannol in bone marrow-derived macrophages (BMDMs). In addition, due to the poor bioavailability and pharmacokinetics of small-molecule tyrosine kinase inhibitors and superiority of targeting nanoparticles-based drug delivery system, we herein prepared piceatannol-encapsulated poly(lactic-co-glycolic acid) nanoparticles that conjugated with chemokine C-C motif ligand 4 (P-NPs-C) and studied its therapeutic effects in vitro in BMDMs and in vivo in experimental colitis model. Our results indicated that in addition to alleviating colitis, oral administration of P-NPs-C promoted the restoration of intestinal barrier function and improved intestinal microflora dysbiosis, which represents a promising treatment for IBD.

JINLING (Judicious INdex of Luminal INflammation Grade) score, an effective indicator to assess inflammation severity in Crohn's disease.

BACKGROUND: With the increasing demand for individualized treatment in Crohn's disease, a score for accurate evaluation of inflammation grade will be of great significance. We have developed the JINLING score to assess inflammation severity for Crohn's disease, which incorporates an endoscopic score (SES-CD) and a 2-item patient-reported outcome (PRO2). The aim of this study was to examine the performance of JINLING score in evaluating inflammation grade and the correlation with the clinical outcomes. METHODS: The correlation between JINLING score and Global Histologic Disease Activity Score (GHAS), fecal calprotectin (FCP), and C-reactive protein (CRP) level was performed in an exploration phase with a retrospective data set. The data on clinical outcomes including medication effects, Crohn's disease-related surgery and biochemical results were collected from a single-center prospective validation cohort. RESULTS: JINLING score correlated significantly with FCP, CRP, and hemoglobin in the exploration cohort (all P < 0.05). The receiver operating characteristic (ROC) curves based on a threshold Crohn's disease activity index value of 150, GHAS of 4, and FCP of 60 µg/g to identify disease activity, all showed a higher area under the curve with JINLING score than SES-CD or PRO2 alone. In the validation cohort, patients with high inflammation grade (JINLING ≥4) had higher GHAS, CRP, and FCP than low inflammation grade patients. High JINLING score was associated with an increased risk of treatment failure (hazard ratio 2.93; 95% confidence interval 1.13-7.61, P = 0.021). CONCLUSION: This newly developed index served well for quantifying inflammation grade and predicting clinical outcomes. JINLING score has the potential to facilitate clinical decision-making and personalized therapy for Crohn's disease patients.

Deresuscitation in Patients with Abdominal Sepsis Carries a Lower Mortality Rate and Less Organ Dysfunction than Conservative Fluid Management.

Background: The relation between deresuscitative fluid management after the resuscitation phase and clinical outcome in patients with abdominal sepsis is not completely clear. The aim of this study was to assess the contribution of deresuscitative management to death and organ dysfunction in abdominal sepsis. Methods: Consecutive patients with abdominal sepsis requiring fluid resuscitation were included in this study. According to the fluid management given in the later stage of resuscitation, a conservative group and a deresuscitative fluid management group were compared. The primary outcome was in-hospital death, whereas secondary outcomes were categorized as organ dysfunction and other adverse events. Results: A total of 138 patients were enrolled in this study. Conservative fluid management was given to 47.8% of patients, whereas deresuscitative fluid management occurred in 52.2%. The deresuscitative strategy was associated with a markedly lower prevalence of new-onset acute kidney injury and a decrease in the duration of continuous renal replacement therapy (CRRT). There was a greater risk of needing new-onset intubation and the mechanical ventilation duration in the conservative group than in the deresuscitative group. However, the deresuscitative group did not differ from the conservative group with respect to open abdomen and intra-abdominal hypertension or new-onset abdominal compartment syndrome. The conservative treatment was associated with prolonged stays as well as a higher in-hospital mortality rate. A multivariable logistic regression model showed that deresuscitative fluid management imparts a protective effect against in-hospital death (odds ratio 4.343; 95% confidence interva1 1.466-12.866; p = 0.008), whereas septic shock, source control failure, and CRRT duration were associated with a higher mortality rate. Conclusions: Fluid balance achieved using deresuscitative treatment is correlated with better outcomes in patients with abdominal sepsis, indicating that this treatment may be useful as a therapeutic strategy.

Early Enteral Nutrition Preserves Intestinal Barrier Function through Reducing the Formation of Neutrophil Extracellular Traps (NETs) in Critically Ill Surgical Patients.

BACKGROUND: The gut was suggested as the driver of critical illness and organ injury. Recently, excessive formation of neutrophil extracellular traps (NETs) was associated with mucosal inflammation. Direct investigation of intestinal mucosa is essential to illuminate the potential mechanism of gut barrier in critically ill patients. We hypothesized that early enteral nutrition (EN) could decrease intestinal NETs and maintain the gut barrier. METHODS: Intestinal biopsies were obtained using biopsy forceps from critically ill surgical patients complicated with enterocutaneous fistula. Expressions of tight junction (TJ) proteins, mucosal inflammation, and apoptosis were evaluated. Moreover, NET-associated proteins were evaluated in intestinal specimens of patients by Western blot and immunofluorescence analysis. RESULTS: The intestinal barrier was significantly impaired in critically ill patients receiving early total parenteral nutrition (TPN), evidenced by intestinal villi atrophy, inflammatory infiltration, increased enterocyte apoptosis, and abnormal TJ expressions. Early EN significantly alleviated these intestinal injuries. In addition, we observed increased formation of the NET structure and elevated expressions of NET-associated proteins in intestines of critically ill surgical patients. Early EN was associated with the diminished presence of NETs and reduced expression of NET-associated proteins. Mechanically, analysis of the TLR4 pathway showed a significant increase in TLR4, NFκB, and MAPK signaling in patients receiving TPN when compared to those receiving early EN. CONCLUSION: The intestinal barrier is disrupted in the human gut during critical illness. Our data suggests that an increased NET structure was showed in the gut of critically ill surgical patients, and early EN treatment was associated with the reduction of NET formation and the preservation of mucosal immunity.

Nutritional Management of Patients With Enterocutaneous Fistulas: Practice and Progression.

The management of enterocutaneous fistulas (ECF) can be challenging because of massive fluid loss, which can lead to electrolyte imbalance, severe dehydration, malnutrition and sepsis. Nutritional support plays a key role in the management and successful closure of ECF. The principle of nutritional support for patients with ECF should be giving enteral nutrition (EN) priority, supplemented by parenteral nutrition if necessary. Although total parenteral nutrition (TPN) may be indicated, use of enteral feeding should be advocated as early as possible if patients are tolerant to it, which can protect gut mucosal barrier and prevent bacterial translocation. A variety of methods of enteral nutrition have been developed such as fistuloclysis and relay perfusion. ECF can also be occluded by special devices and then EN can be implemented, including fibrin glue application, Over-The-Scope Clip placement and three-dimensional (3D)-printed patient-personalized fistula stent implantation. However, those above should not be conducted in acute fistulas, because tissues are edematous and perforation could easily occur.

Current progress of source control in the management of intra-abdominal infections.

Intra-abdominal infection (IAI) is a deadly condition in which the outcome is associated with urgent diagnosis, assessment and management, including fluid resuscitation, antibiotic administration while obtaining further laboratory results, attaining precise measurements of hemodynamic status, and pursuing source control. This last item makes abdominal sepsis a unique treatment challenge. Delayed or inadequate source control is an independent predictor of poor outcomes and recognizing source control failure is often difficult or impossible. Further complicating issue in the debate is surrounding the timing, adequacy, and procedures of source control. This review evaluated and summarized the current approach and challenges in IAI management, which are the future research directions.

Early Active Irrigation-Suction Drainage among Enterocutaneous Fistulas Patients with Chronic Critical Illness: A Retrospective Cohort Study.

Enterocutaneous fistulas (ECFs) requiring admission to ICU is a serious surgical complication. A growing number of patients survive ECFs but remain chronically critically ill. The aim of our study was to investigate the risk factors of hospital death in patients with chronic critical illness attributed to ECFs. A retrospective single-center study was conducted in 163 ECF patients between 2013 and 2017. Patient-specific baseline characteristics, outcomes, and process of care variables were collected. Risk factors for hospital mortality were determined using univariate and multivariate analyses. Patients were divided into the following two groups according to the hospital discharge outcome: group survivors (n = 106) and group nonsurvivors (n = 57). Patients who received active irrigation-suction drainage (AISD) within 24 hours after the diagnosis of ECFs had a significantly lower hospital mortality rate than those who received AISD after more than 24 hours (17.9% vs 46.9%, P < 0.001). Multivariate logistic regression analysis demonstrated that delayed AISD (adjusted odds ratio [AOR], 10.24; 95% confidence interval [CI], 3.03-34.59; P < 0.001) and no rehabilitation therapy (AOR, 4.77; 95% CI, 1.43-15.98; P = 0.011) were independently associated with a greater risk of hospital mortality. The hospital mortality rate in patients with more than or equal to four risk factors was 92.6 per cent (n = 57), compared with a mortality rate of 9.4 per cent (n = 106) in patients who did not have these risk factors (P < 0.001). The risk of hospital death is exceptionally high among patients with chronic critical illness attributed to ECFs. Efforts aimed at early AISD and rehabilitation therapy are likely to be associated with improved clinical outcomes.

Mincle/Syk Signalling Promotes Intestinal Mucosal Inflammation Through Induction of Macrophage Pyroptosis in Crohn's Disease.

BACKGROUND: Macrophage-inducible C-type lectin [Mincle] signalling plays a proinflammatory role in different organs such as the brain and liver, but its role in intestinal inflammation, including Crohn's disease [CD], remains unknown. METHODS: The characteristics of Mincle signalling expression in CD patients and experimental colitis were examined. The functional role of Mincle signalling in the intestine was addressed in experimental colitis models in vivo by using Mincle knock-out [Mincle-/-] mice. In addition, neutralising anti-Mincle antibody, downstream spleen tyrosine kinase [Syk] inhibitor, and Mincle pharmacological agonist were used to study the Mincle signalling in intestine. Bone marrow-derived macrophages were collected from mice and used to further verify the effect of Mincle signalling in macrophages. RESULTS: This study has shown that Mincle signalling was significantly elevated in active human CD and experimental colitis, and macrophages were the principal leukocyte subset that upregulate Mincle signalling. Mincle deficiency and Syk pharmacological inhibition ameliorated the colitis by reducing induced macrophage pyroptosis, and activation of Mincle with the agonist aggravated the intestinal inflammation. The ex vivo studies demonstrated that activation of Mincle signalling promoted the release of proinflammatory cytokines, whereas its absence restricted release of proinflammatory cytokines from pyroptosis of macrophages. In addition, Mincle/Syk signalling in macrophages could promote the production of chemokines to recruit neutrophils by activating mitogen-activated protein kinase [MAPK] during intestinal inflammation. CONCLUSIONS: Mincle signalling promotes intestinal mucosal inflammation by inducing macrophage pyroptosis. Modulation of the Mincle/Syk axis emerges as a potential therapeutic strategy to target inflammation and treat CD.

Follistatin like protein-1 modulates macrophage polarization and aggravates dextran sodium sulfate-induced colitis.

Follistatin-like protein 1 (FSTL1) is a pleiotropic cytokine involved in multiple processes including organ development, carcinogenesis, metastasis and so on. Some recent studies have suggested a possible role of FSTL1 in the inflammatory diseases. We for the first time tried to unravel its effect on the colitis, and explore the possible mechanisms. Here we found that FSTL1 was upregulated in active human and murine colitis. It facilitated proinflammatory M1 polarization of macrophages and inhibited the M2 anti-inflammatory phenotype, leading to excessive production of multiple inflammatory cytokines in vitro and in vivo. Haplodeletion of FSTL1 in mice significantly reduced the clinical and histological activity of colitis. Most importantly, macrophage depletion diminished the difference between DSS-treated WT and FSTL1+/- mice. Altogether, our results suggested that FSTL1 may also serve as an important contributor in the colonic inflammation. The possible mechanism may be related to its modulation on macrophage polarization.