Dietary n‑3 polyunsaturated fatty acid (PUFA) exerts anti‑inflammatory and immunoregulatory effects via downregulation of the innate and adaptive immune responses. However, the effect of dietary n‑3 PUFA on experimental Crohn's Disease (CD) in rats and the underlying mechanisms are unclear. The present study aimed to investigate the effects of n‑3 PUFA on CD induced by 2,4,6‑trinitrobenzene sulfonic acid (TNBS) in rats, and to determine the underlying mechanisms, including the peroxisome proliferator‑activated receptor (PPAR)‑γ and nuclear factor of activated T‑cells (NFAT) pathway. Sprague‑Dawley rats (n=90) were randomly assigned to the following groups: Control (intragastric distilled water); PUFA control (intragastric n‑3 PUFA, 20 mg/kg/day); trans‑fatty acid (TFA) control (intragastric TFA, 13 mg/kg/day); model (intragastric distilled water + TNBS); PUFA model (intragastric n‑3 PUFA, 20 mg/kg/day + TNBS); and TFA model (intragastric TFA, 13 mg/kg/day + TNBS). The disease activity index (DAI), colon macroscopic damage index (CMDI) and tissue damage index (TDI) were evaluated. The expression of PPAR‑γ, NFAT, interleukin (IL)‑4 and IL‑2 mRNA in colonic tissues was determined by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR), and the serum levels of IL‑6, IL‑12, tumor necrosis factor‑α and interferon‑γ were measured by ELISA. The results demonstrated that dietary n‑3 PUFA markedly attenuated colonic inflammation compared with the model group, as indicated by reduced DAI, CMDI and TDI scores, amelioration in pathological evaluation and improvements in localized mucosal inflammation, as indicated by the levels of cytokines associated with local mucosal immunity. Treatment with n‑3 PUFA increased the gene expression of PPAR‑γ in TNBS‑treated rats, and reduced the expression of NFAT, which ultimately reduced the release of IL‑4 and IL‑2 detected by RT‑qPCR. A TFA‑enriched diet was observed to increase DAI and TDI scores, aggravate pathological inflammation with epithelioid granulomas and enhance the release of proinflammatory cytokines, compared with the model group. In conclusion, the present study demonstrated that dietary n‑3 PUFA may attenuate experimental CD induced by TNBS in rats by regulating the expression and activity of the PPAR‑γ/NFAT signaling pathway. These results provide a promising potential therapeutic method for the treatment of CD.
Aim: Mucosal melanomas are highly malignant tumors that are of great interest for their aggressive
behaviour and unfavourable prognosis, which could be the result of many reasons. In this paper, we describe
a retrospective study performed to investigate the characteristics and prognoses of gastrointestinal mucosal
melanomas in a Chinese population to help future clinicians recognize the prognosis of this disease.
Methods: We retrospectively studied 49 patients diagnosed with gastrointestinal mucosal melanomas.
Multivariate analysis of prognosis and overall survival (OS) was performed using the Cox proportional
hazards model.
Results: The multivariate analysis showed that the condition of the primary or metastatic tumor and tumor
location were independent factors that affected the prognosis of patients with gastrointestinal mucosal
melanomas. Patients with metastatic tumors had a better prognosis than patients with primary tumors, and
tumors that occurred in the lower gastrointestinal tract had a better prognosis than those that occurred in the
upper gastrointestinal tract.
Conclusion: Tumor location and the condition of the primary or metastatic tumor may be independent
factors that affect the prognosis of patients with gastrointestinal mucosal melanomas.
stenosis in the future. Pre-endoscopic treatment for AIS has high safety and definite short-term efficacy, which can improve the prognosis and the quality of life of patients. The longterm effect needs to be further followed up.
Background Ustekinumab (UST), a newly-used biologics targeting p40 subunit of IL12 and IL23 in China, exerts confirmed therapeutic effect in induction and maintenance therapy of refractory Crohn's disease (CD). Therapeutic drug monitoring based on trough and antibody concentration is of core importance when treating patients who lose response to UST. We aimed to analyze UST exposure-response relationship in CD treatment. Methods We retrospectively enrolled CD patients with UST administration between March 1, 2020 and May 31, 2021 at IBD center of the Sun Yat-Sun Affiliated Sixth Hospital. Baseline characteristic information, biomarker examination, clinical outcomes determined by Crohn¢s disease activity index (CDAI), and endoscopic outcomes evaluated by a simple endoscopic score for Crohn¢ s disease (SES-CD)at week 16/20 week were collected. The optimal UST trough concentration was identified by receiver-operating characteristic curve (ROC). Results Nineteen eligible patients were finally included, with mean ages as 29.19.1 and mean disease durations as 5.54.7. At study initiation, 89.5% patients had been exposure to prior biologics, 42.1% had previous CD-related surgeries, and 52.6% had a perianal disease. At week 16/20 after UST initiation, clinical response, clinical remission, endoscopic response, and endoscopic remission were 89.5%, 84.2%, 42.2%, and 73.7%, respectively. The cut-off optimal trough concentration of UST was 1.12mg/mL evaluated by ROC with AUC as 0.78, sensitivity as 87.5%, and specificity as 72.7% (IDDF2021-ABS-0055 Figure 1. Receiver-operating curve analysis for endoscopic remission based on UST trough concentration with optimal UST trough level cut-offs of 1.12 mg/mL). Patients with a UST trough concentration > 1.12mg/mL had a significantly higher rate of endoscopic remission than those without (70.0% vs. 11.1%, P =0.02) (IDDF2021-ABS-0055 Figure 2. Clinical and endoscopic outcomes based on UST trough concentration). Conclusions UST is an effective therapy weapon dealing with refractory CD. Trough concentration of UST above 1.12 mg/ml was associated with endoscopic remission at week 16/20 after UST initiation.
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