BACKGROUNDObstructive colorectal cancer (OCC) is always accompanied by severe complications, and the optimal strategy for patients with OCC remains undetermined. Different from emergency surgery (ES), self-expandable metal stents (SEMS) as a bridge to surgery (BTS), could increase the likelihood of primary anastomosis. However, the stent failure and related complications might give rise to a high recurrence rate. Few studies have focused on the indications for either method, and the relationship between preoperative inflammation indexes and the prognosis of OCC is still underestimated.AIMTo explore the indications for ES and BTS in OCCs based on preoperative inflammation indexes.METHODSOne hundred and twenty-eight patients who underwent ES or BTS from 2008 to 2015 were enrolled. Receiver operating characteristic (ROC) curve analysis was used to define the optimal preoperative inflammation index and its cutoff point. Kaplan–Meier analyses and Cox proportional hazards models were applied to assess the association between the preoperative inflammation indexes and the survival outcomes [overall survival (OS) and disease-free survival (DFS)]. Stratification analysis was performed to identify the subgroups that would benefit from ES or BTS.RESULTSOS and DFS were comparable between the ES and BTS groups (P > 0.05). ROC curve analysis showed derived neutrophil-to-lymphocyte ratio (dNLR) as the optimal biomarker for the prediction of DFS in ES (P < 0.05). Lymphocyte-to-monocyte ratio (LMR) was recommended for BTS with regard to OS and DFS (P < 0.05). dNLR was related to stoma construction (P = 0.001), pneumonia (P = 0.054), and DFS (P = 0.009) in ES. LMR was closely related to lymph node invasion (LVI) (P = 0.009), OS (P = 0.020), and DFS (P = 0.046) in the BTS group. dNLR was an independent risk factor for ES in both OS (P = 0.032) and DFS (P = 0.016). LMR affected OS (P = 0.053) and DFS (P = 0.052) in the BTS group. LMR could differentiate the OS between the ES and BTS groups (P < 0.05).CONCLUSIONPreoperative dNLR and LMR could predict OS and DFS in patients undergoing ES and BTS, respectively. For OCC, as the potential benefit group, patients with a low LMR might be preferred for BTS via SEMS insertion.

Tumor necrosis factor-α (TNF-α) is a highly pleiotropic cytokine executing biological functions as diverse as cell proliferation, metabolic activation, inflammatory responses, and cell death. TNF-α can induce multiple mechanisms to initiate apoptosis in hepatocytes leading to the subsequent liver injury. Since the phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) pathway is known to have a protective role in death factor-mediated apoptosis, it is our hypothesis that activation of Akt may represent a therapeutic strategy to alleviate TNF-α-induced hepatocyte apoptosis and liver injury. We report here that the Akt activator SC79 protects hepatocytes from TNF-α-induced apoptosis and protects mice from d-galactosamine (d-Gal)/lipopolysaccharide (LPS)-induced TNF-α-mediated liver injury and damage. SC79 not only enhances the nuclear factor-κB (NF-κB) prosurvival signaling in response to TNF-α stimulation, but also increases the expression of cellular FLICE (FADD-like IL-1β-converting enzyme)-inhibitory protein L and S (FLIPL/S), which consequently inhibits the activation of procaspase-8. Furthermore, pretreatment of the PI3K/Akt inhibitor LY294002 reverses all the SC79-induced hepatoprotective effects. These results strongly indicate that SC79 protects against TNF-α-induced hepatocyte apoptosis and suggests that SC79 is likely a promising therapeutic agent for ameliorating the development of liver injury. NEW & NOTEWORTHY SC79 protects hepatocytes from TNF-α-mediated apoptosis and mice from Gal/LPS-induced liver injury and damage. Cytoprotective effects of SC79 against TNF-α act through both AKT-mediated activation of NF-κB and upregulation of FLIPL/S.

Attenuated heart rate recovery is associated with an increased risk of diabetes in a dose-dependent manner, and measurement of heart rate recovery is worth recommending as part of diabetes risk assessment in clinical routines.

Xiao-man Dai and Yan-hui Zhang contributed equally to this work.

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