BACKGROUND The role of the positive end-expiratory pressure (PEEP) and lung recruitment manoeuvre (LRM) combination (termed open-lung strategy, OLS) during intra-operative mechanical ventilation is not clear. OBJECTIVE To determine whether an open-lung strategy constituting medium PEEP (6–8 cmH 2 O) and repeated LRMs protects against postoperative complications in at-risk patients undergoing laparoscopic colorectal cancer resection under low-tidal-volume ventilation. DESIGN A prospective, assessor-blinded, randomised controlled trial. SETTING Single university-affiliated hospital, conducted from January 2017 to October 2018. PATIENTS A total of 280 patients at risk of pulmonary complications, scheduled for laparoscopic colorectal cancer resection under general anaesthesia and low-tidal-volume (6–8 ml kg −1 predicted body weight) ventilation. INTERVENTION The patients were randomly assigned (1 : 1) to a PEEP of 6–8 cmH 2 O with LRMs repeated every 30 min (OLS group) or a zero PEEP without LRMs (non-OLS group). MAIN OUTCOME MEASURES The primary outcome was a composite of major pulmonary and extrapulmonary complications occurring within 7 days after surgery. The secondary outcomes included intra-operative potentially harmful hypotension and the need for vasopressors. RESULTS A total of 130 patients from each group were included in the primary outcome analysis. Primary outcome events occurred in 24 patients (18.5%) in the OLS group and 43 patients (33.1%) in the non-OLS group [relative risk, 0.46; 95% confidence interval (CI), 0.26 to 0.82; P = 0.009). More patients in the OLS group developed potentially harmful hypotension (OLS vs. non-OLS, 15% vs. 4.3%; P = 0.004) and needed vasopressors (25% vs. 8.6%; P < 0.001). CONCLUSION Among at-risk patients undergoing laparoscopic colorectal cancer resection under low-tidal-volume ventilation, an open-lung strategy with a PEEP of 6–8 cmH 2 O and repeated LRMs reduced postoperative complications compared with a strategy using zero PEEP without LRMs. Of note, LRMs should be used with caution in patients with haemodynamic instability. TRIAL REGISTRATION Clinicaltrials.gov identifier: NCT03160144.

The protective mechanism underlying remote ischemic preconditioning (RIPC) is unclear. This study aims to verify whether the protein expression profile in the serum could be altered by RIPC and to detect potential protein mediators. Transient limb ischemia consisting of three cycles of 5-min ischemia followed by 5-min reperfusion was performed on sixty healthy volunteers. Serum samples were collected at 30 min before transient limb ischemia and at 1 hour (h), 3 h, 8 h, 24 h, and 48 h after completion of three cycles. Changes in the serum protein profile were analyzed by two-dimensional gel electrophoresis and proteins were identified by MALDI-TOF/TOF mass spectrometry. Fourteen differentially expressed proteins were identified and, respectively, involved in immune system, lipid binding and metabolism, apoptosis, and blood coagulation. Complement C3, vitronectin, and apolipoprotein A-I were further confirmed by western blotting, and the results showed that their contents decreased significantly after transient limb ischemia. It is concluded that transient limb ischemia alters the serum protein expression profile in human being, and that reduction of serum contents of complement C3 and vitronectin may represent an important part of the mechanism whereby RIPC confers its protection.

Background The tumor immune microenvironment is one of the most important prognostic factors in liver metastasis from colorectal cancer. Low-dose cyclophosphamide (CTX) is widely believed to be involved in the modulation of the immune system. However, the underlying mechanism of low-dose CTX remains unknown. This study aimed to investigate the antitumor immunity of low-dose CTX in the treatment of colon-cancer liver metastasis. Methods Thirty mice were randomly divided into five groups. After liver metastasis was established in colon-cancer models, mice in the treatment groups were injected with low-dose CTX (20 mg/kg) at different time points. Liver and spleen tissues were examined for T-cell markers via flow cytometry. Interleukin (IL)-10 and transforming growth factor (TGF)-β1 expression levels in liver tissues were analysed by immunohistochemistry. Serum interferon (IFN)-γ and IL-10 levels were detected by enzyme-linked immunosorbent assay. An additional 20 mice were randomly allocated into two groups and the survival times were recorded. Results The expression levels of CD4+ T cells, CD8+ T cells, and IFN-γ were down-regulated, whereas those of IL-10 and TGF-β1 were up-regulated in liver metastasis from colon cancer in mice. Furthermore, the local and systemic microenvironments of the liver were altered, which led to reduced antitumor immune responses and subsequently liver metastasis. However, treatment with low-dose CTX reversed these effects. The survival times of mice treated with low-dose CTX were significantly longer than those of the other groups. Conclusions Low-dose CTX exerts its antitumor activity by changing the systemic and local immune microenvironments and enhancing immune regulation in mice. CTX could be used as a drug to prevent and treat liver metastasis from colon cancer.

Background: Endothelial dysfunction, the initial pathogenic factor in atherosclerosis, can be alleviated via transient limb ischemia. We observed the effects of regular transient limb ischemia (RTLI) on atherosclerosis in hypercholesterolemic rabbits. Methods: Twenty-eight rabbits were randomized to control, cholesterol, sham, ischemia groups ( n = 7 each) between October 2010 and March 2011. They were fed a normal diet in the control group and hypercholesterolemic diet in other groups for 12 weeks. Six cycles of RTLI were performed once per day on the ischemia group. Serum samples were prepared to measure the total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) before the experiment (W0), at the end of weeks 4, 8, 12 (W4, W8, W12). The whole aorta was harvested at W12 and stained using Sudan IV to identify the plaque. The plaque area was measured using Image J. Results were analyzed by analysis of variance or rank sum test. Results: Concentrations of TC in the cholesterol group were higher than those in the control group at W4 (29.60 [23.75, 39.30] vs. 1.00 [0.80, 1.55], Z = –2.745, P = 0.006), W8 (41.78 [28.08, 47.37] vs. 0.35 [0.10, 0.68], Z = –2.739, P = 0.006), W12 (48.32 [40.04, 48.95] vs. 0.61 [0.50, 0.86], Z = –2.739, P = 0.006). Similar results were obtained for HDL-C and LDL-C. Serum concentrations of TC, HDL-C, and LDL-C in the hypercholesterolemic groups had no differences (all P > 0.05). The percentage of plaque area in the cholesterol group was higher than that in the control group (47.22 ± 23.89% vs. 0, Z = –2.986, P = 0.003). Square root of the percentage of plaque area was smaller in the ischemia group than that in the cholesterol (0.44 ± 0.13 vs. 0.67 ± 0.18, P = 0.014) or sham groups (0.44 ± 0.13 vs. 0.61 ± 0.12, P = 0.049). Conclusion: In hypercholesterolemic rabbits, RTLI might prevent atherosclerosis progression by reducing the percentage of plaque area.

Colorectal cancer (CRC) is the third and second most common type of cancer diagnosed in males and females, respectively, and is the fourth leading cause of cancer-associated mortality worldwide. Liver metastasis is the primary cause of mortality in patients with CRC, and therefore requires therapeutic focus. Regulatory T cells (Tregs) and hepatic stellate cells (HSCs) are potentially involved in regulating the immune response during liver metastasis. The aim of the present study was to evaluate the influence of CD4 + forkhead box p3 (Foxp3) + Tregs and the HGF/c-Met signaling pathway in the liver metastasis of CRC. A model of the latter was established using Balb/c mice via splenic injection of human CRC cells (CT-26 line). The mice were monitored for 3 weeks after being injected, and the spleens and livers were removed on day 22 for further analysis. Moreover, the single-cell suspensions were labeled with CD4 and Foxp3 antibodies, and were analyzed using flow cytometry. Expression levels of α-smooth muscle actin (SMA), hepatocyte growth factor (HGF) and hepatocyte growth factor receptor (c-Met) were analyzed using immunohistochemistry. Mice injected with CT-26 cells exhibited signs of illness and significant weight loss, compared with the control mice (P=0.013), and they also developed liver metastases, at an average of 20.5 tumors per mouse. Pathological evaluation using hematoxylin and eosin staining confirmed the tumors as liver metastases of CRC. The numbers of CD4 + T cells were significantly decreased in the spleen (P<0.001) and liver (P=0.003) of tumor-bearing mice, while the proportions of CD4 + FOXP3 + Tregs increased significantly in the spleen (P<0.001) and liver (P=0.026) compared with that in the controls. Additionally, α-SMA, HGF and c-Met levels increased significantly during metastatic growth in the liver. In conclusion, CD4 + FOXP3 + Treg levels increased and the HGF/c-Met pathway was up regulated during the liver metastasis of CRC in mice, indicating the presence of potential therapeutic targets.