Circulating and intestinal regulatory T cells in inflammatory bowel disease: A systemic review and meta-analysis.

Regulatory T cells (Tregs) play an important immunosuppressive role in inflammatory bowel disease (IBD). However, findings on the quantitative and functional changes of intestinal and circulating Tregs in patients with IBD are rather contradictory. We therefore conducted a meta-analysis on this issue. The pooled effect was assessed using the standardized mean difference (SMD) with a 95% confidence interval (CI), and subgroup analyses were performed to investigate heterogeneity. This analysis included 764 IBD (402 UC and 362 CD) patients and 341 healthy controls (HCs) pooled from 17 eligible studies. The percentage of circulating Tregs was significantly decreased in active IBD patients compared to HCs (SMD = -0.95, p < 0.001) and inactive IBD patients (SMD = -0.80, p < 0.001). There was no difference in the percentage of circulating Tregs between inactive IBD patients and HCs. The suppressive function of circulating Tregs was impaired in active IBD patients according to limited data (SMD = -0.75, p = 0.02). Besides, the percentage of intestinal Tregs was significantly higher in inflamed regions than in non-inflamed regions (SMD = 0.85, p < 0.001). Our study quantitatively summarized the quantitative and functional changes of Tregs and supported the therapeutic potential of Tregs in IBD. Moreover, additional research into the functions and characteristics of intestinal Tregs in IBD is needed.

Inflammatory bowel disease is a group of diseases in which the intestines are repeatedly inflamed. Regulatory T cells are a subset of immune cells that have been found to migrate from the blood and lymphoid tissues into the intestine to act as a suppressor of inflammation in inflammatory bowel disease. However, previous research on changes in the amount and function of regulatory T cells in the blood and intestine of patients with inflammatory bowel disease revealed inconsistent results. Therefore, we used a "meta-analysis" approach to integrate the results of previous studies to obtain an overall picture of Changes in regulatory T cell percentages and function. We found that patients with active inflammatory bowel disease had a lower proportion of blood regulatory T cells and a poorer ability to suppress inflammation compared to healthy individuals. In the intestine of patients with inflammatory bowel disease, a higher proportion of regulatory T cells are found in inflamed sites than in non-inflamed sites. However, compared to other intestinal inflammatory diseases, such as intestinal tuberculosis, patients with inflammatory bowel disease have a lower tendency of elevated proportions of intestinal regulatory T cells. In some ways, our study quantitatively summarized the conflicting results of the quantitative and functional changes of Tregs and supported the therapeutic potential of Tregs in IBD. Moreover, additional research into the functions and characteristics of intestinal Tregs in IBD is needed.

Predictors and optimal management of tumor necrosis factor antagonist nonresponse in inflammatory bowel disease: A literature review.

Tumor necrosis factor-α (TNF-α) antagonists, the first biologics approved for treating patients with inflammatory bowel disease (IBD), are effective for the induction and maintenance of remission and significantly improving prognosis. However, up to one-third of treated patients show primary nonresponse (PNR) to anti-TNF-α therapies, and 23%-50% of IBD patients experience loss of response (LOR) to these biologics during subsequent treatment. There is still no recognized predictor for evaluating the efficacy of anti-TNF drugs. This review summarizes the existing predictors of PNR and LOR to anti-TNF in IBD patients. Most predictors remain controversial, and only previous surgical history, disease manifestations, drug concentrations, antidrug antibodies, serum albumin, some biologic markers, and some genetic markers may be potentially predictive. In addition, we also discuss the next steps of treatment for patients with PNR or LOR to TNF antagonists. Therapeutic drug monitoring plays an important role in treatment selection. Dose escalation, combination therapy, switching to a different anti-TNF drug, or switching to a biologic with a different mechanism of action can be selected based on the concentration of the drug and/or antidrug antibodies.

Symptoms of anxiety and depression associated with steroid efficacy and clinical outcomes in patients with inflammatory bowel disease.

Background: Anxiety and depression symptoms are very common in patients with inflammatory bowel disease (IBD). We aimed to explore the impact of anxiety and depression on the efficacy of medications, as well as IBD-related poor outcomes. Method: This was a prospective longitudinal observational study. Hospital Anxiety and Depression Scale was used to assess anxiety and depression symptoms. Logistic regression analyses were used to assess the association between anxiety/depression and the response to different medications. Kaplan-Meier survival analysis and Cox regression model were applied to analyze the relationship between anxiety/depression and IBD-related poor outcomes, which were defined as urgent IBD-related hospitalization, IBD-related surgery, or death. Results: A total of 325 IBD patients were enrolled, 118 of whom were treated with corticosteroids, 88 with azathioprine/6-mercaptopurine (AZA/6-MP), and 147 with anti-TNF agents. Anxiety/depression symptoms were found to be significantly related to steroid resistance, but independent of AZA/6-MP and anti-TNF agents nonresponse. There was a significant association between anxiety/depression symptoms and IBD-related poor outcomes. Coexisting with anxiety/depression symptoms was an independent influencing factor of steroid resistance and IBD-related poor outcomes. Conclusion: IBD patients with anxiety/depression symptoms were at a higher risk of developing steroid resistance and IBD-related poor outcomes. Future studies are needed to explore whether interventions for anxiety and depression will improve their response to medications and change their prognosis.

Change of monocytes/macrophages in ulcerative colitis patients with symptoms of anxiety and depression.

BACKGROUND AND AIMS: Monocytes/macrophages play important roles in inflammatory bowel disease and depression, but few studies had focused on the change of monocytes/macrophages in ulcerative colitis (UC) patients with psychiatric disorders. METHODS: UC patients were divided into two groups based on the Hospital Anxiety and Depression Scale (HADS). Demographic and clinical data were captured. Peripheral blood samples and intestinal biopsies were collected for the analysis of monocyte immunophenotype, phagocytic function, and CD4 + T cell differentiation. Transmission electron microscopy was used to observe the ultrastructure of intestinal macrophages. RESULTS: A total of 139 UC patients were included. 37.41% and 32.37% of UC patients had symptoms of anxiety and depression. In patients with symptoms of anxiety/depression, mayo score, platelet count, erythrocyte sedimentation rate, and endoscopic score, histological scores were significantly higher than those in UC patients without. In patients with symptoms of anxiety/depression, the percentages of CD14 + + CD16 + monocytes and CD14 + CD16++ monocytes were higher, and the phagocytosis was decreased. Patients with symptoms of anxiety/depression had more CD68 + cells and higher M1/M2 ratios in the intestine mucosal layer compared to those without. CONCLUSIONS: Monocytes and intestinal macrophages from UC patients with anxiety/depression tended to polarize to pro-inflammatory subtypes, and their function was also impaired.

Depression Exacerbates Dextran Sulfate Sodium-Induced Colitis via IRF5-Mediated Macrophage Polarization.

BACKGROUND AND AIMS: Patients with inflammatory bowel disease (IBD) and concurrent depression are predisposed to severer disease activity and a worse prognosis. Macrophage polarization toward the M1 phenotype may contribute to the exacerbation of IBD with comorbid depression. Moreover, interferon regulatory factor 5 (IRF5) is involved in the pathogenesis of IBD. The aim of this study was to explore the role of IRF5 in macrophage polarization in the impact of depression upon colitis. METHODS: Depressive-like behavior was induced by repeated forced swim stress. Colon length, disease activity index (DAI), colon morphology, histology, ultrastructure of epithelial barrier, lamina propria macrophage polarization, and expression of IRF5 were compared between DSS colitis rats with and without depressive-like behavior. IRF5 shRNA was constructed to affect the rat peritoneal macrophages polarization in vitro. After IRF5 shRNA lentivirus was introduced into colon by enema, the colitis severity, lamina propria macrophage polarization, and TNF-α, IL-1ß, and IL-10 of colon tissues were measured. RESULTS: The study found severer colonic inflammation in depressed versus non-depressed DSS-colitis rats. Depressed DSS-colitis rats exhibited smaller subepithelial macrophages size and reduced intracellular granule diversity compared with nondepressed DSS-colitis rats. Increased polarization toward the M1 phenotype, elevated expression of IRF5, and co-expression of IRF5 with CD86 were found in depressed versus nondepressed DSS-colitis rats. Lentivirus-mediated shRNA interference with IRF5 expression switched rat peritoneal macrophage polarization from the M1 to the M2 phenotype, downregulated TNF-α, IL-1ß expression to a greater extent in depressed versus nondepressed colitis rats. CONCLUSIONS: IRF5-mediated macrophage polarization may likely underlie the deterioration of DSS-induced colitis caused by depression.

Venlafaxine as an Adjuvant Therapy for Inflammatory Bowel Disease Patients With Anxious and Depressive Symptoms: A Randomized Controlled Trial.

Background and Aims: The effect of antidepressant therapy on Inflammatory Bowel Disease (IBD) remains controversial. This trial aimed to assess whether adding venlafaxine to standard therapy for IBD improved the quality of life (QoL), mental health, and disease activity of patients with IBD with anxious and depressive symptoms. Methods: A prospective, randomized, double-blind, and placebo-controlled clinical trial was conducted. Participants diagnosed with IBD with symptoms of anxiety or depression were randomly assigned to receive either venlafaxine 150 mg daily or equivalent placebo and followed for 6 months. Inflammatory Bowel Disease Questionnaire (IBDQ), Mayo score, Crohn's disease activity index (CDAI), Hospital Anxiety and Depression Scale (HADS), and blood examination were completed before the enrollment, during, and after the follow-up. Mixed linear models and univariate analyses were used to compare groups. Results: Forty-five patients with IBD were included, of whom 25 were randomized to receive venlafaxine. The mean age was 40.00 (SD = 13.12) years old and 25 (55.6%) were male. Venlafaxine showed a significant improvement on QoL (p < 0.001) and disease course (p = 0.035), a greater reduction in HADS (anxiety: p < 0.001, depression: p < 0.001), Mayo scores (p < 0.001), and CDAI (p = 0.006) after 6 months. Venlafaxine had no effect on IL-10 expression, endoscopic scores, relapse rate, and use rate of biologics and corticosteroids, but did reduce serum level of erythrocyte estimation rate (ESR; p = 0.003), C-reactive protein (CRP; p < 0.001) and tumor necrosis factor-α (TNF-α; p = 0.009). Conclusions: Venlafaxine has a significantly beneficial effect on QoL, IBD activity, and mental health in patients with IBD with comorbid anxious or depressive symptoms. (Chinese Clinical Trial Registry, ID: ChiCTR1900021496).

SARS-CoV-2-inactivated vaccine hesitancy and the safety in inflammatory bowel disease patients: a single-center study.

Background: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine is thought to be the most effective preventive method of controlling the coronavirus disease 2019 (COVID-19) epidemic. Some patients with immune-related diseases, including inflammatory bowel disease (IBD) patients, however, may hesitate to be vaccinated for various reasons. Although several guidelines recommend vaccinating all IBD patients with inactivated SARS-CoV-2 vaccines, there is still a lack of real-world data on the safety of inactivated SARS-CoV-2 vaccines and COVID-19 vaccination rate in IBD patients. In this study, we investigated the reasons for hesitancy in COVID-19 vaccination, the COVID-19 vaccination rate, and the safety of SARS-CoV-2-inactivated vaccination in patients with IBD. Methods: This was a retrospective study. A total of 418 participants with IBD were enrolled to calculate the vaccination rates. A total of 232 patients with IBD who did not receive SARS-CoV-2 vaccination were recruited to investigate the reasons for hesitation. A follow-up survey of 151 IBD patients and 188 healthy participants who had received the SARS-CoV-2-inactivated vaccination was conducted to analyze adverse reactions. Results: The COVID-19 vaccination rate was 49.3% and almost half of the participants were 'Concerned about the safety of the vaccine (such as adverse reactions) due to IBD'. After SARS-CoV-2 vaccination, adverse reactions were mild or moderate. The adverse reactions in the IBD and non-IBD populations were roughly the same, and IBD medications did not increase the risk of adverse reactions. Conclusion: SARS-CoV-2-inactivated vaccination rates in IBD patients are still low and a significant proportion of patients are hesitant about the vaccine because of safety concerns. SARS-CoV-2-inactivated vaccination in patients with IBD appears to be safe.

Symptoms of anxiety/depression is associated with more aggressive inflammatory bowel disease.

Studies have demonstrated that inflammatory bowel disease (IBD) patients are at an increased risk of developing anxiety and/or depression. IBD patients with depression/anxiety have higher rates of hospitalization and increased disease severity than those without. So far, there is a paucity of data concerning the impact of anxiety/depression on Chinese IBD patients. The aim of this study was to find out the prevalence of symptoms of anxiety/depression in Chinese IBD population and its impact on IBD-related features. This is a cross-sectional study from the southwest China IBD referral center. Eligible participants were divided into those with symptoms of anxiety/depression and those without based on the Hospital Anxiety and Depression Scale (HADS). Demographic data and disease duration, IBD-related surgery, tobacco use, extra-intestinal manifestations, disease activity scores, endoscopic evaluation, laboratory data and current medication use were compared between two groups. A total of 341 IBD patients [221 Crohn's disease (CD) and 120 ulcerative colitis (UC)] were included. The prevalence of symptoms of anxiety/depression in IBD was 33.1%. CD patients with symptoms of anxiety/depression tended to have higher scores of simple endoscopic scores for Crohn's disease (SES-CD) (p = 0.0005). UC patients with symptoms of anxiety/depression had a significantly higher Mayo score (p = 0.0017) and ulcerative colitis endoscopic index of severity (UCEIS) (p < 0.0001) than their non-anxiety/depression counterparts. CD-related surgery (p = 0.012) and Crohn's disease activity index (CDAI) (p < 0.0001) were identified as independent risk factors for symptoms of anxiety/depression in CD, while corticosteroid use (p = 0.036) as an independent risk factor for symptoms of anxiety/depression in UC. This study helps our understanding of the prevalence of symptoms of anxiety/depression in IBD patients and its impact on IBD course and reminds us to pay more attention on IBD management with anxiety/depression.

Differential diagnostic ability of 18F-FDG PET/CT radiomics features between renal cell carcinoma and renal lymphoma.

BACKGROUND: The aim of this study is to determine the differential diagnostic value of texture parameters of PET/CT on renal cell carcinoma and renal lymphoma. METHODS: Twenty renal lymphoma and 18 renal cell carcinoma (RCC) patients were analyzed in this study. The pathological information and basic characteristics were extracted from the electronic medical record system of our hospital. We used LIFEx package to extract data from the radiomics images. Receiver operating characteristic analysis and binary logistic regression analysis was applied in determining the diagnostic accuracy of texture parameters as well as the synthetic parameter, of which the sensitivity and specificity was improved. RESULTS: There were 14 (two in Histogram, two in Grey Level Co-occurrence Matrix, five in Grey-Level Run Length Matrix, five in Grey-Level Zone Length Matrix) out of the texture parameters showing an area under the curve (AUC) >0.7 and P<0.05. Synthesized parameters of each section showed even higher differentiation ability, with AUC varying from 0.725 to 1.000. CONCLUSIONS: Texture analysis of 18F-FDG PET/CT could effectively differentiate between RCCs and renal lymphomas.

Layer-by-Layer Decorated Nanoscale ZIF-8 with High Curcumin Loading Effectively Inactivates Gram-Negative and Gram-Positive Bacteria.

Bacteria-mediated infectious diseases have become a health-care challenge globally since the development of antibiotic resistance. Reactive oxygen species produced by photosensitizers have great potential in fighting bacterial infections, especially against Gram-negative bacteria that are hard to kill by regular methods owing to their formidable defensive membrane structures under the premise of avoiding overuse of antibiotics. In this work, a small molecular photosensitizer, curcumin (CCM), was used as a model and encapsulated into zeolitic imidazolate framework-8 (ZIF-8). Then the ZIF-8 loaded with CCM (CCM@ZIF-8) was decorated with biocompatible polymers hyaluronic acid (HA) and chitosan (CS) by the layer-by-layer self-assembly technique to yeild in an antibacterial CCM@ZIF-8@HA@CS nanoparticle with a high local positive charge density and is capable of binding the surface of bacteria by electrostatic interactions. The CCM drug loading capability of the nanoparticle was found to be as high as 10.89%. Upon exposure to blue light (72 J/cm2) for 10 min, the minimum inhibitory concentration and minimum bactericidal concentration of CCM@ZIF-8@HA@CS against Gram-positive bacteria (G(+)) Staphylococcus aureus (S. aureus) and Gram-negative bacteria (G(-)) Escherichia coli (E. coli) were the same, which were as low as 0.625 and 2.5 µg/mL, respectively, showing highly effective antibacterial activities. After treatment with CCM@ZIF-8@HA@CS under blue-light irradiation, the membranes of S. aureus and E. coli folded and cracked. Importantly, the antibacterial agent showed good biocompatibility in the cytotoxicity test using L929 cells and hemolysis test using rabbit blood cells under blue-light irradiation. Therefore, this CCM@ZIF-8@HA@CS nanocomposite is expected to find application in the treatment of superficial traumatic and refractory chronic infections caused by G(+) and G(-).

Diversified gut microbiota in newborns of mothers with gestational diabetes mellitus.

Gestational diabetes mellitus (GDM), a high-risk pregnancy complication of great effect on the perinatal health of women and newborns, may cause changes of gut microbiota in mothers and further affect gut microbiota in newborns. This study aimed to investigate the potential effect of mother GDM on newborns' gut microbiota. Meconium DNA was extracted from a total of 34 full-term and C-sectioned newborns, in which 20 newborns had mothers diagnosed with GDM, while 14 had unaffected mothers. Sequencing and bioinformatics analysis of 16S rRNA indicated that the gut microbiota of GDM newborns showed differences compared to control newborns. The taxonomy analyses suggested that the overall bacterial content significantly differed by maternal diabetes status, with the microbiome of the GDM group showing lower alpha-diversity than that of control group. The phyla of Proteobacteria and Actinobacteria in GDM newborns increased, while that of Bacteroidetes significantly reduced (P<0.05). Moreover, several unique gut microbiota in phylum of Proteobacteria, Firmicutes, Actinobacteria, Bacteroidetes, Chloroflexi, Acidobacteria, and Planctomycetes found in control newborns were absent in GDM ones. At genus level, the relative abundance of Prevotella and Lactobacillus significantly decreased (P<0.05) in GDM newborns. Correlation analysis indicated that maternal fasting glucose levels were positively correlated with the relative abundance of phylum Actinobacteria and genus Acinetobacter, while negatively correlated with that of phylum Bacteroidetes and genus Prevotella. However, bacteria in GDM grade A2 (GDM_A2) newborns did not show any statistical variation compared to those from control newborns, which might be attributed to the additional intervention by insulin. The results of this study have important implications for understanding the potential effects of GDM on the gut microbiota of newborns and thus possibly their metabolism at later stages in their lives.