RESUMO
Background: Peripheral blood test is a routine clinical examination item. Granulocytes and platelets are often used to measure the severity of inflammatory response, and it is worthy to investigate the value of various inflammatory indices ratio for predicting the prognosis of disease. Aims: To compare and analyze the diagnostic efficacy of platelet to lymphocyte ratio (PLR), neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), red blood cell distribution width to platelet ratio (RPR), C-reactive protein to lymphocyte ratio (CLR) and C-reactive protein (CRP) in evaluating the severity of hyperlipidemic acute pancreatitis (HLAP). Methods: The clinical and laboratory data of 104 patients with HLAP from January 2018 to December 2020 at the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. According to the revised Atlanta classification, HLAP patients were divided into mild HLAP, moderate to severe/severe HLAP. Forty-four healthy subjects during the same period were served as the controls. PLR, NLR, MLR, RPR, CLR and CRP were compared between HLAP group and control group. The ROC curve was used to analyze the diagnostic efficacy of PLR, NLR, MLR, RPR, CLR and CRP for the diagnosis of moderate to severe/severe HLAP. Results: PLR, NLR, MLR, RPR, CLR and CRP were significantly increased in HLAP group than in control group (P<0.05); PLR, NLR, MLR, RPR, CLR and CRP were significantly increased in moderate to severe/severe HLAP group than in mild HLAP group (P<0.05). The cut-off values of PLR, NLR, MLR, RPR, CLR, CRP and combined PLR, NLR, MLR, RPR, CLR were 220.48, 10.95, 0.84, 0.12, 76.66, 87.44 mg/L, 0.37, respectively, the sensitivity for diagnosing moderate to severe/severe HLAP were 0.73, 0.45, 0.47, 0.82, 0.65, 0.65 and 0.88, respectively, the specificity were 0.85, 0.87, 0.90, 0.81, 0.83, 0.83 and 0.85, respectively, AUC were 0.84, 0.65, 0.67, 0.87, 0.77, 0.75 and 0.94, respectively. Conclusions: PLR, NLR, MLR, RPR, CLR and CRP can evaluate the severity of HLAP, and the combined PLR, NLR, MLR, RPR and CLR has higher sensitivity and diagnostic efficacy in the diagnosis of moderate to severe/severe HLAP.
RESUMO
Imipenem is a carbapenem antibiotic. However, Imipenem could not be marketed owing to its instability and nephrotoxicity until cilastatin, an inhibitor of renal dehydropeptidase-I (DHP-I), was developed. In present study, the potential roles of renal organic anion transporters (OATs) in alleviating the nephrotoxicity of imipenem by cilastatin were investigated and in rabbits. Our results indicated that imipenem and cilastatin were substrates of hOAT1 and hOAT3. Cilastatin inhibited hOAT1/3-mediated transport of imipenem with IC values comparable to the clinical concentration, suggesting the potential to cause a clinical drug-drug interaction (DDI). Moreover, imipenem exhibited hOAT1/3-dependent cytotoxicity, which was alleviated by cilastatin and probenecid. Furthermore, cilastatin and probenecid ameliorated imipenem-induced rabbit acute kidney injury, and reduced the renal secretion of imipenem. Cilastatin and probenecid inhibited intracellular accumulation of imipenem and sequentially decreased the nephrocyte toxicity in rabbit primary proximal tubule cells. Renal OATs, besides DHP-I, was also the target of interaction between imipenem and cilastatin, and contributed to the nephrotoxicity of imipenem. This therefore gives in part the explanation about the mechanism by which cilastatin protected against imipenem-induced nephrotoxicity. Thus, OATs can potentially be used as a therapeutic target to avoid the renal adverse reaction of imipenem in clinic.