Whether blood transfusion exacerbates cancer outcomes after surgery in humans remains inconclusive. We utilized a large cohort to investigate the effect of perioperative blood transfusion on cancer prognosis following colorectal cancer (CRC) resection. Patients with stage I through III CRC undergoing tumour resection at a tertiary medical center between 2005 and 2014 were identified and evaluated through August 2016. Propensity score matching was used to cancel out imbalances in patient characteristics. Postoperative disease-free survival (DFS) and overall survival (OS) were analysed using Cox regression model. A total of 4,030 and 972 patients were analysed before and after propensity score matching. Cox regression analyses demonstrated blood transfusion associated with shorter DFS and OS before and after matching (hazard ratio: 1.41, 95% CI: 1.2–1.66 for DFS; 1.97, 95% CI: 1.6–2.43 for OS). Larger transfusion volume was linked to higher overall mortality (≤4 units vs. nil, HR = 1.58; >4 units vs. nil, HR = 2.32) but not more cancer recurrence. Preoperative anemia was not associated with decreased survival after adjusting covariates. Perioperative blood transfusion was associated with worse cancer prognosis after curative colorectal resection, independently of anemia status. Strategies aimed at minimizing transfusion requirements should be further developed.

Pupil dilation is consistently evoked by affective and cognitive processing, and this dilation can result from sympathetic activation or parasympathetic inhibition. The relative contributions of the sympathetic and parasympathetic systems on the pupillary response induced by emotion and cognition may be different. Sympathetic and parasympathetic activity is regulated by global luminance level. Higher luminance levels lead to greater activation of the parasympathetic system while lower luminance levels lead to greater activation of the sympathetic system. To understand the contributions of the sympathetic and parasympathetic nervous systems to pupillary responses associated with emotion and saccade preparation, emotional auditory stimuli were presented following the fixation cue whose color indicated instruction to perform a pro- or anti-saccade while varying the background luminance level. Pupil dilation was evoked by emotional auditory stimuli and modulated by arousal level. More importantly, greater pupil dilation was observed with a dark background, compared to a bright background. In contrast, pupil dilation responses associated with saccade preparation were larger with the bright background than the dark background. Together, these results suggest that arousal-induced pupil dilation was mainly mediated by sympathetic activation, but pupil dilation related to saccade preparation was primarily mediated by parasympathetic inhibition.

Nitric oxide (NO) can regulate osteoblast activity. In this study, we evaluated the effects of pretreatment with a low concentration of NO on osteoblast injuries induced by a high level of NO and its possible molecular mechanisms. Exposure of osteoblasts to 0.3 mM sodium nitroprusside (SNP), an NO donor, slightly increased cellular NO levels without affecting cell viability. SNP at 2 mM greatly increased the levels of cellular NO and reactive oxygen species, and induced osteoblast death. Thus, osteoblasts were treated with 0.3 and 2 mM SNP as the sources of low and high NO, respectively. Exposure of osteoblasts to high NO decreased alkaline phosphatase (ALP) activity and cell viability, and induced cell apoptosis. With low-NO pretreatment, the high NOinduced cell insults were significantly ameliorated. When the culture medium was totally replaced after pretreatment with low NO, the protective effects obviously decreased. Administration of high NO significantly decreased c-Jun N-terminal kinase (JNK) phosphorylation and nuclear c-Jun levels. Meanwhile, pretreatment with low NO significantly alleviated the high NO-induced reduction in activation of JNK and c-Jun. Sequentially, high NO inhibited Bcl-2 mRNA and protein synthesis. After pretreatment with low NO, the high NO-induced inhibition of the production of Bcl-2 mRNA and protein significantly decreased. Imaging analysis from confocal microscopy further revealed that high NO decreased translocation of the Bcl-2 protein from the cytoplasm to mitochondria. However, pretreatment with low NO significantly ameliorated the high NO-induced suppression of Bcl-2 0 s translocation. Exposure of human osteoblasts to high NO significantly decreased ALP activity and cell viability, and induced cell apoptosis. Pretreatment with low NO significantly lowered the high NO-induced alterations in ALP activity, cell viability, and cell apoptosis. This study shows that pretreatment with low NO can protect osteoblasts from high NOinduced cell insults via JNK/c-Jun-mediated regulation of Bcl-2 gene expression and protein translocation. ß

Summary There is conflicting evidence whether allogeneic blood transfusion influences survival or cancer recurrence after resection of hepatocellular cancer. We followed up 1469 patients who had undergone hepatocellular resection for a median (IQR [range]) of 45 (21–78 [0–162]) months, of whom 626 (43%) had had blood transfusion within 7 days of surgery. Both disease‐free survival and patient survival were measured using a proportional hazards regression model and inverse probability of treatment weighting. We used restricted cubic splines for the association of the number of packed red blood cell units transfused with cancer recurrence and survival. We found that peri‐operative blood transfusion was independently associated with survival and cancer recurrence after resection of hepatocellular carcinoma. Adjusted hazard ratios (95%CI) for the association of blood transfusion with cancer recurrence and all‐cause mortality were 1.3 (1.1–1.4) and 1.9 (1.6–2.3), p < 0.001 for both. With more units transfused cancer recurrence was more likely and survival was shorter. The association of the number of transfused units was non‐linear for cancer recurrence and linear response for all‐cause mortality.