Cystathionine gamma-lyase (Cth) induces efferocytosis in macrophages via ERK1/2 to modulate intestinal barrier repair.

BACKGROUND: The inflammatory response induced by intestinal ischaemia‒reperfusion injury (I/R) is closely associated with infectious complications and mortality in critically ill patients, and the timely and effective clearance of apoptotic cells is an important part of reducing the inflammatory response. Studies have shown that the efferocytosis by phagocytes plays an important role. Recently, studies using small intestine organoid models showed that macrophage efferocytosis could promote the repair capacity of the intestinal epithelium. However, no studies have reported efferocytosis in the repair of I/R in animal models. RESULTS: We used an in vivo efferocytosis assay and discovered that macrophage efferocytosis played an indispensable role in repairing and maintaining intestinal barrier function after I/R. In addition, the specific molecular mechanism that induced macrophage efferocytosis was Cth-ERK1/2 dependent. We found that Cth drove macrophage efferocytosis in vivo and in vitro. Overexpression/silencing Cth promoted/inhibited the ERK1/2 pathway, respectively, which in turn affected efferocytosis and mediated intestinal barrier recovery. In addition, we found that the levels of Cth and macrophage efferocytosis were positively correlated with the recovery of intestinal function in clinical patients. CONCLUSION: Cth can activate the ERK1/2 signalling pathway, induce macrophage efferocytosis, and thus promote intestinal barrier repair. Video Abstract.

Appraisal of the diagnostic procedures of acute pancreatitis in the guidelines.

OBJECTIVES: The purpose of this study was to comprehensively assess the heterogeneity of procedures in the diagnostic guidelines for acute pancreatitis and to identify gaps limiting knowledge in diagnosing this disease. METHODS: A systematic search of a number of databases was performed to determine the guidelines for the diagnosis of acute pancreatitis in patients with severe pancreatitis. The guidelines for the diagnosis of severe pancreatitis were evaluated by AGREE II. The Measurement Scale of Rate of Agreement (MSRA) was used to assess the guidelines (2015-2020) and extract evidence supporting these recommendations for analysis. RESULTS: Seven diagnostic guidelines for acute pancreatitis were included. Only the 2019 WSES Guidelines for the Management of Severe Acute Pancreatitis and the Japanese Guidelines for the Management of Acute Pancreatitis: Japanese Guidelines 2015 had a total score of more than 60%, which is worthy of clinical recommendation. The average scores of the Scope and Purpose domain and the Clarity and Expression domain were the highest at 71.62% and 75.59%, respectively, while the average score of the Applicability area was the lowest at 16.67%. The included guidelines were further analyzed to determine the heterogeneity of the diagnosis of acute pancreatitis. The main reasons for the heterogeneity were the citation of low-quality evidence, the presence of far too many indicators for the classification of acute pancreatitis, unclear depictions of the standard, and poorly comprehensive recommendations for the diagnosis of the aetiology in the primary diagnosis of acute pancreatitis, the severity classification, the aetiological diagnosis, and the diagnosis of comorbidities. CONCLUSIONS: The quality of different diagnostic guidelines for severe pancreatitis is uneven. The recommendations are largely based on low-quality evidence, and the guidelines still have much room for improvement to reach a high level of quality. The diagnostic procedures for acute pancreatitis vary widely in different guidelines. There are large differences between them, and resolving the abovementioned reasons would be a very wise choice for guideline developers to revise and upgrade the guidelines in the future.

Evaluation of guidelines for the management of perianal fistulas in Crohn's disease.

INTRODUCTION: The occurrence of perineal fistula is a significant evesnt in the evolution of Crohn's disease. Approximately 21% to 23% of patients develop perineal fistula at least once in their lifetime, approximately 30% of patients have cases of recurrence, and the refractory and recurrent perineal lesions of Crohn's disease impose a great economic burden on patients. The main purpose of this review was to investigate the quality of guidelines for perineal fistula in Crohn's disease. AREA COVERED: Relevant websites and databases were systematically searched to identify and select clinical guidelines related to perineal fistulas in Crohn's disease. Four independent reviewers assessed the eligible guidelines using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) and used intraclass correlation coefficients (ICC) to measure the agreement among the guideline reviewers. CONCLUSION: There is much room for improvement in the quality of guidelines for the management of perineal fistulas in Crohn's disease. The recommendations and evidence for guidelines for the management of perineal fistulas in Crohn's disease are quite heterogeneous, and guideline-developers would be well advised to address the above issues during future guideline development.