To assess the effect of enteral nutrition (EN) supplemented with glutamine on recovery after ileal pouch-anal anastomosis (IPAA) in rats, to provide an experimental basis for nutritional support in patients with ulcerative colitis (UC) after IPAA.Male Sprague-Dawley (SD) rats were randomly divided into three groups (n = 8) after IPAA operation using a microsurgical technique. From the third postoperative day, rats in the control group, EN group, and immune nutrition (IN) group were fed standard rat chow, short peptide EN, and short peptide EN combined with glutamine ad libitum, respectively. The rats' general condition was observed throughout the study. Serum levels of total protein (TP), albumin (ALB), prealbumin (PA), and transferrin (TF) were detected on the 30th postoperative day, using an automatic biochemical analyzer. The ileal pouch mucosa was stained with hematoxylin and eosin (HE), and occludin protein levels were detected by immunohistochemistry.The body weight of rats in the EN group (359.20 ± 10.06 g) was significantly higher than that in the control group (344.00 ± 9.66 g) (P < 0.05) and lower than that in the IN group (373.60 ± 9.86 g) (P < 0.05) on the 30th postoperative day. The levels of serum TP, ALB, PA, and TF in the EN group were significantly higher than those in the control group (P < 0.01 for all) and lower than those in the IN group (P < 0.05 for all). Histopathological score (EN: 0.80 ± 0.37; IN: 0.60 ± 0.40; control group: 2.29 ± 0.18) and expression level of occludin protein (EN: 0.182 ± 0.054; IN: 0.188 ± 0.048; control group: 0.127 ± 0.032) were significantly lower in the control group compared with the EN and IN groups (P < 0.05 for all), but there were no significant differences between the latter two groups (P > 0.05 for all).EN combined with glutamine may effectively improve nutritional status after IPAA. Our results suggest a benefit of glutamine supplementation in EN for UC patients undergoing IPAA, although human studies are required to confirm this finding.
Polo-like kinase 4 (PLK4) involves in tumor progression via regulating centriole duplication. This study aimed to investigate correlations of PLK4 with tumor characteristics and survival in cutaneous melanoma patients undergoing surgical resection. Tumor specimens of 43 patients were retrieved for PLK4 determination by immunohistochemistry (IHC). The IHC score was a multiplication of staining intensity and percentage of staining-positive cells. This study found the median and mean tumor PLK4 IHC score was 0.0 (interquartile range: 0.0-6.0) and 3.5 ± 3.2 (mean ± SD), respectively. Elevated tumor PLK4 IHC score correlated with lymph node metastasis (P = 0.028), higher tumor node metastasis (TNM) stage (P = 0.004), and adjuvant therapy (P =0.029). Tumor PLK4 IHC score > 0 did not relate to disease-free survival (DFS) or overall survival (OS) (both P > 0.050). Tumor PLK4 IHC score > 3 associated with decreased DFS (P = 0.027), but not OS (P = 0.098). Five-year DFS rate of patients with tumor PLK4 IHC score = 0 and > 0 was 75.0% and 53.9%, correspondingly; while the rate of patients with the score ≤ 3 and > 3 was 81.0% and 37.5%, respectively. Five-year OS rate of patients with the score = 0 and > 0 was 100.0% and 66.3%, accordingly; whereas the rate of patients with the score ≤ 3 and > 3 was 85.7% and 61.5%, correspondingly. According to forward-step multivariate analysis, neither the score > 0 nor > 3 independently related to worse DFS and OS (all P > 0.050). Further validation via THE HUMAN PROTEIN ATLAS database showed high PLK4 RNA expression associated with shortened OS in melanoma patients (P = 0.001). PLK4 correlates with lymph node metastasis, increased TNM stage, and poor DFS in cutaneous melanoma patients undergoing surgical resection.
AIMTo assess the therapeutic potential of Lactobacillus acidophilus (LA) for the treatment of pouchitis in a rat model. METHODSSprague Dawley rats underwent proctocolectomy and ileal pouch-anal anastomosis followed by administration of dextran sulfate sodium (DSS) to induce pouchitis.Rats with pouchitis were randomly divided into three groups: no intervention (NI), normal saline (NS, 3 mL/d normal saline for 7 d), and LA (3 mL/d LA at 1 × 10 10 colony-forming units for 7 d).General body condition was recorded and pouch specimens were obtained for histological examination.mRNA expression levels of interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor-α were determined by RT-PCR.Zonula occludens protein 1 (ZO-1) levels were measured by immunohistochemistry. RESULTSLA reduced weight loss associated with pouchitis (P < 0.05) and improved the symptoms of pouchitis in rats.Compared with the NI and NS groups, rats in the LA
Transient receptor potential vanilloid 4 (TRPV4) plays a role in regulating pulmonary fibrosis (PF). While several TRPV4 antagonists including magnolol (MAG), have been discovered, the mechanism of action is not fully understood. This study aimed to investigate the effect of MAG on alleviating fibrosis in chronic obstructive pulmonary disease (COPD) based on TRPV4, and to further analyze its mechanism of action on TRPV4. COPD was induced using cigarette smoke and LPS. The therapeutic effect of MAG on COPD-induced fibrosis was evaluated. TRPV4 was identified as the main target protein of MAG using target protein capture with MAG probe and drug affinity response target stability assay. The binding sites of MAG at TRPV4 were analyzed using molecular docking and small molecule interaction with TRPV4-ankyrin repeat domain (ARD). The effects of MAG on TRPV4 membrane distribution and channel activity were analyzed by co-immunoprecipitation, fluorescence co-localization, and living cell assay of calcium levels. By targeting TRPV4-ARD, MAG disrupted the binding between phosphatidylinositol 3 kinase γ and TRPV4, leading to hampered membrane distribution on fibroblasts. Additionally, MAG competitively impaired ATP binding to TRPV4-ARD, inhibiting TRPV4 channel opening activity. MAG effectively blocked the fibrotic process caused by mechanical or inflammatory signals, thus alleviating PF in COPD. Targeting TRPV4-ARD presents a novel treatment strategy for PF in COPD.
Abstract Background Infliximab (IFX) is a breakthrough treatment for refractory Crohn’s disease (CD) whose effect on postoperative complications of CD remains controversial. The purpose of this study was to conduct a meta-analysis examining the effect of IFX on postoperative complications of CD. Methods We searched “PubMed,” “EMBASE,” and “Cochrane Library” databases from inception of each database until March 2018. All eligible articles were screened according to the inclusion criteria. The cumulative overall, major, minor, infectious, noninfectious, surgical, and medical complications, as well as reoperation, readmission, and mortality of CD patients who received IFX and underwent ileocolonic resection were extracted and analyzed using Review Manager 5.3. The random effects model was used to calculate the odds ratio (OR) and 95% confidence interval (CI). Results A total of 18 nonrandomized controlled trial studies, with 1407 patients who received IFX and 4589 patients who did not were identified. The incidence of complications was 9.38%–60.56% in the IFX group and 12.73%–53.85% in the control group. Overall, major, minor, infectious, noninfectious, surgical, and medical complications could be assessed in 16, 12, 11, 14, 12, 12, and 11 studies, respectively. There were no statistically significant differences between the 2 groups for any complication (P > 0.05, all comparisons). Reoperation (P = 0.70), readmission (P = 0.22) and mortality (P = 0.86) showed no significant difference between the 2 groups. Subgroup analysis showed that complications were not significantly different among the countries represented in the studies. Conclusions Based on this analysis, there does not appear to be an association between preoperative IFX treatment and postoperative complications of CD; IFX appears relatively safe for preoperative use in the treatment of CD.
Pouchitis occurs in approximately 50% of patients with ulcerative colitis after ileal pouch–anal anastomosis (IPAA) but the pathogenesis remains unclear. We used a rat model of dextran sulfate sodium (DSS)–induced ileal pouchitis to examine whether intestinal barrier disruption plays a role in the development and progression of the disease. Rats were randomly divided into DSS (underwent IPAA and administered 5% DSS orally), IPAA (underwent IPAA), and Sham groups (underwent switch abdominal surgery). In the DSS group, levofloxacin intervention and nonintervention subgroups were used to determine the influence of antibiotics on intestinal barrier dysfunction. Hematochezia and fecal scores were recorded. Ileum and pouch specimens were obtained for histological assessment. Immunohistochemistry was performed for myeloperoxidase and occludin protein expression. Levels of interleukin-1β (IL-1β), IL-6, IL-10, and tumor necrosis factor α mRNA were detected by real-time PCR. Plasma D-lactate concentrations were determined with colorimetry. Only rats in the DSS group experienced hematochezia, and their fecal and histological scores significantly increased (P < 0.01). Compared with the IPAA and Sham groups, levels of myeloperoxidase, IL-1β, IL-6, tumor necrosis factor α, and plasma D-lactate significantly increased, whereas occludin and IL-10 reduced in the DSS group (P < 0.01). The levofloxacin subgroup showed increased occludin expression and more balanced inflammatory cytokine levels than the nonintervention subgroup. All differences showed linear correlations. The intestinal barrier was disrupted in this rat model of pouchitis. Increased proinflammatory and decreased anti-inflammatory factors aggravated the intestinal barrier damage. Antibiotics may ameliorate this process.
Background Metformin and statins are commonly used globally for the treatment of type 2 diabetes mellitus and dyslipidemia, respectively. Recently, multiple novel pathways have been discovered, which may contribute to the treatment of various types of cancer. Several meta-analysis studies have reported that the use of metformin or statins is associated with a lower risk of colon cancer compared to nonusers. In this study, our aim was to perform a meta-analysis and investigate the prognostic roles of these two medications in colon cancer. Methods To identify relevant articles, literature searches were performed in the PubMed and Web of Science databases using a combination of keywords related to metformin, statins and colon cancer prognosis until August 2023. The study utilized STATA 12.0 software (Stata Corporation, College Station, Texas, USA) to compute all the hazard ratios (HRs) and 95% confidence intervals (CIs) regarding the association between metformin or statin uses and prognostic-related outcomes. Results Our analysis revealed that the use of metformin was associated with a significantly lower overall mortality of colon cancer (HR = 0.63; 95% CI = 0.51–0.77; I 2 = 94.9%; P < 0.001), as well as lower cancer-specific mortality of colon cancer (HR = 0.68; 95% CI = 0.50–0.94; I 2 = 91.9%; P < 0.001). Similarly, the use of statins was also associated with a lower overall mortality of colon cancer (HR = 0.68; 95% CI = 0.60–0.78; I 2 = 93.8%; P < 0.001), as well as a lower cancer-specific mortality of colon cancer (HR = 0.74; 95% CI = 0.67–0.81; I 2 = 82.2%; P < 0.001). Conclusion Our meta-analysis study suggests that statins and metformin may have potential as adjuvant agents with significant benefits in the prognosis of colon cancer.
Objective
To explore the effects of intra-abdominal fat (IAF) on postoperative complications of Crohn′s disease (CD) .
Methods
Clinical data of 50 CD patients undergoing abdominal surgery at the Department of General Surgery, Tianjin Medical University General Hospital from May 2008 to April 2017 were retrospectively analyzed. Meanwhile the CT images of these patients were collected. Image J software was used to measure the IAF of patients before surgery. These patients were divided into with postoperative complication group (16 cases) and without postoperative complication group (34 cases) and clinical characters of these two groups were compared. The risk factors of postoperative complication were analyzed by Logistic regression.
Results
Of 50 CD patients, 16 developed postoperative complications and the morbidity was 32.0%. As compared to without postoperative complication group, with postoperative complication group had longer disease course[ (6.9 ±5.0) years vs. (3.0 ±2.7) years, P = 0.008], higher ratio of preoperative emergent complication (81.3% vs. 52.9%, P = 0.040) , lower serum albumin level [ (29.8 ±4.2) g/L vs. (34.2 ±6.5) g/L, P = 0.007], less area of IAF[ (3044.6 ±1125.4) vs. (4271.5 ±1830.6) , P = 0.006] and higher ratio of intestinal non-side-to-side anastomosis (56.2% vs 20.6%, P = 0.021) . Multivariate Logistic regression analysis showed that IAF less than 3000 (OR: 9.743, 95% CI: 1.508 to 62.943) , non-side-to-side anastomosis (OR: 6.843, 95%CI: 1.126 to 41.572) and emergent operation (OR: 6.981, 95% CI: 1.086 to 44.876) were independent risk factors of postoperative complications of CD.
Conclusion
IAF is an independent risk factor of postoperative complication of CD, suggesting that the IAF can be used as an evaluation index for postoperative complications.
Key words:
Intra-abdominal fat; Crohn′s disease; Surgery; Complication
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