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Epithelial regeneration is essential for homeostasis and mucosal barrier repair. In this study, we aimed to define the effect of IL-10 on mucosal healing. Intestinal stem cells (ISCs) cultures and mice were treated with recombinant mice IL-10 (rmIL-10). The level of cell proliferation, differentiation, death and related signaling pathways for self-renewal of ISCs were measured in vitro and in vivo. It was uncovered that rmIL-10 increased the size and death, but reduced the total number of organoids. In addition, rmIL-10 depleted Lgr5+ ISCs and reduced epithelial proliferation, but enhanced the differentiation of epithelial cells and expanded numbers of transit-amplifying (TA) cells. These changes are related to the decrease of Wnt and Notch signals in vivo and in vitro. Meanwhile, increased expression of Paneth cells and decreased expression of enteroendocrine cells and goblet cells were induced by rmIL-10. Thus, our data indicate that IL-10 reduces the survival of Lgr5+ ISCs and proliferation of epithelial cells by inhibiting Notch and Wnt signaling, but promotes enhanced the differentiation of epithelial cells and expanded numbers of TA cells. Therefore, IL-10 acts as an anti-inflammatory factor, but may damage intestinal mucosa repair and maybe a potential target for the treatment of intestinal injury.

Intestinal ischemia/reperfusion (I/R) injury is a serious clinical event that may induce intestinal mucosal injury, whose major underlying mechanisms include reactive oxygen species (ROS) generation, release of inflammatory mediators and induction of apoptosis. Irisin is considered an agent with potent protection against many pathological injures. The aim of this study was to investigate the protective effect of irisin pretreatment on intestinal injury and explore its underlying mechanisms in a mouse model of intestinal I/R injury as well as a cell model (IEC-6 cell) of hypoxia/reoxygenation (H/R). The results showed that irisin pretreatment ameliorated I/R and H/R-induced injury in vivo and in vitro. In addition, irisin reduced the levels of tumor necrosis factor (TNF)-α, interleukin(IL)-1β and interleukin(IL)-6 in the intestine. Compared with the I/R group, irisin pretreatment effectively reduced malondialdehyde (MDA) and myeloperoxidase (MPO) levels, but increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in the intestine, and significantly reduced oxidative stress. Furthermore, irisin pretreatment downregulated Bax and cleaved Caspase-3 at the protein level, and increased Bcl-2 protein amounts, significantly reducing apoptosis in the intestine of I/R mice. Moreover, both in vivo and in vitro results showed that irisin pretreatment significantly upregulated nuclear factor (erythroid-derived 2)-like 2 (Nrf2) protein. Meanwhile, Nrf2 siRNA treatment partially abrogated the protective effects of irisin pretreatment on H/R induced cellular damage, inflammatory response, oxidative stress, and apoptosis in IEC-6 cells. These findings suggest that irisin pretreatment improves I/R-induced intestinal inflammatory response, reduces oxidative stress and inhibits apoptosis, which could be, at least partially, associated with Nrf2 pathway activation.

The occurrence and progress of minimal hepatic encephalopathy (MHE) is closely related to the inflammatory response; however, inflammation contributes to behavioral abnormalities and sleep disorders. Dexmedetomidine has anti-inflammatory effects against various diseases. Whether dexmedetomidine improves MHE and the underlying mechanism is yet unclear. The present study aimed to explore the effects of dexmedetomidine on sleep structure, neurobehavior, and brain morphology of MHE rats and investigate its underlying mechanism. A rat MHE model was established by intraperitoneal injection of thioacetamide (TAA). Dexmedetomidine or yohimbine was administered intraperitoneally to investigate the role of α2 adrenoreceptor in the protection conferred by dexmedetomidine. The 24-h sleep, neurobehavioral changes, the liver function, blood ammonia and morphological changes of the liver and brain were assessed. Also, the microglia, astrocytes, neurons, the expression of pro-inflammatory factors (IL-1β, TNF-α, IL-18), and NLRP3 inflammasomes were detected. The results showed that marked sleep disorders, cognitive impairment, anxiety, abnormal liver function and pathological damage of liver and brain were detected in the MHE rats. The microglia in the prefrontal cortex was highly activated along with the increased expression of pro-inflammatory factors and NLRP3 inflammasomes. Interestingly, dexmedetomidine improved above indicators, however, yohimbine significantly abolished the protection of dexmedetomidine. These findings showed that dexmedetomidine restored the changes in the sleep disorders and neurobehavior in rats and reduced brain damage. The mechanism might be partially related to the activation of α2 adrenergic receptors, reduction of neuroinflammatory response, and inhibition of the activation of microglia and NLRP3/Caspase1 signaling pathway.

Background Postoperative atrial fibrillation/flutter (POAF) is associated with significant morbidity and mortality after general thoracic surgery, but the need for and the best agent for prophylaxis remains obscure. Methods A systematic literature search was performed to identify randomized controlled trials that compared regimens for POAF prophylaxis after general thoracic surgery. Random-effects meta-analyses with trial sequential analyses were performed to compare the effects of medical prophylaxis vs placebo/usual care. The risk of POAF among patients receiving various prophylactic regimens was subjected to Bayesian network meta-analysis. Results Twenty-two trials (2,891 patients and 11 regimens) were included. Overall, medical prophylaxis reduced the incidence of POAF (OR, 0.33; 95% CI, 0.22-0.49) but not short-term mortality (OR, 0.85; 95% CI, 0.41-1.73). There was no significant difference in patient withdrawal due to adverse events (OR, 1.67; 95% CI, 0.67-4.16). Trial sequential analysis showed that as of 2012, sufficient evidence had accrued in support of the effectiveness of medical prophylaxis in reducing POAF after general thoracic surgery. In network meta-analysis, β-blockers, angiotensin-converting enzyme inhibitors, amiodarone, magnesium, and calcium channel blockers significantly reduced the risk of POAF compared with placebo/usual care. β-Blockers had the highest probability of being the most effective agents (OR, 0.12; 95% credible interval [CrI], 0.05-0.27; probability of being best, 77.7%; number needed to treat, 5.2). Conclusions The current literature supports the effectiveness and tolerability of medical prophylaxis and the superiority of β-blockers in preventing POAF after general thoracic surgery. β-Blockers are recommended, taking into consideration the status of the bronchopulmonary system.

Ribonuclease (RNase) reportedly exerts organ-protective effects in several pathological conditions, including ischemia reperfusion (I/R), but whether it can exhibit protective effect on intestinal I/R injury and potential mechanisms remain unknown. The present study was aimed to evaluate the effects of RNase on intestinal I/R injury and explore the underlying mechanisms. Thirty-two wild-type C57BL/6J adult male mice were evenly divided into a sham group, a sham + RNase group, an I/R group and an I/R + RNase group. Intestinal I/R was produced by clamping the superior mesenteric artery for 1 h followed by reperfusion for 2 h. All mice were treated with 3 doses of RNase or the same dosage of normal saline at different points. It was found that intestinal I/R caused significant intestinal injury and an increase in levels of extracellular RNAs (exRNAs). Treatment with RNase significantly reduced the inflammatory cytokine production, inhibited intestinal apoptosis and down-regulated the expression of toll like receptor 3 in intestinal tissues. In conclusion, increased exRNAs may contribute to intestinal I/R injury in adult mice, and RNase treatment during perioperative window is effective for attenuating intestinal I/R injury.

We assessed whether aortic cross-clamping or limb remote ischemic preconditioning improved postoperative outcomes, reduced myocardial injury and incidences of postoperative complications in patients undergoing on-pump coronary artery bypass grafting (CABG).PubMed, EMBASE, the Cochrane Library, and ClinicalTrials databases were searched for studies comparing the effects of ischemic preconditioning with no preconditioning in adult patients undergoing on-pump CABG. The primary end points were mechanical ventilation time, the length of stay in intensive care unit and hospital, whereas the secondary end points were peak values of myocardial biomarkers and postoperative complications. Mean differences were estimated for the primary end points, as well as standard mean differences and odds ratios for the secondary end points.A total of 29 randomized controlled trials with 1791 patients were included. Compared with control group, aortic cross-clamping preconditioning reduced mechanical ventilation time (mean difference [95% confidence interval {CI}]) (-5.59 h [-9.21 to -1.96]), whereas limb remote ischemic preconditioning was not associated with improvement of postoperative outcomes. For myocardial biomarkers, both aortic cross-clamping and limb remote ischemic preconditioning reduced peak values of myocardial biomarkers (standard mean difference [95% CI]) (-0.48 [-0.81 to -0.14]; -0.19 [-0.36 to -0.02], respectively). Subgroup analysis showed that aortic cross-clamping preconditioning protocols with ischemia episodes5 min did reduce the release of biomarkers (-0.69 [-1.04 to -0.34]) but those with 5 min ischemia episodes elevated them (0.40 [0.04-0.75]). Cardiovascular, cerebrovascular, renal, and intestinal complications were reported, and aortic cross-clamping preconditioning seemed to reduce the incidences of cardiac arrhythmia (odds ratio [95% CI]) (0.46 [0.27-0.80], P = 0.006).Cardiac surgeons could consider aortic cross-clamping or limb remote ischemic preconditioning to reduce myocardial injury during CABG. Moreover, aortic cross-clamping preconditioning is associated with a decreased risk of postoperative respiratory failure and cardiac arrhythmia.

Background: Despite of the importance of gastrointestinal (GI) complications in morbidity and mortality after major and moderate surgeries, it is not yet specifically studied in patients undergoing hepatectomy. This study was aimed to investigate the in-hospital incidence and potential risk factors of GI complications after open hepatectomy in our hospital. Subjects and methods: Prospectively recorded perioperative data from 1329 patients undergoing elective hepatectomy were retrospectively reviewed. The in-hospital incidence of GI complications was investigated, and independent risk factors were analyzed by multiple logistic regression. Results: GI complications occurrence was 46.4%. Univariate analysis showed that preoperative Child-Pugh score, total bilirubin, aspartate transaminase, anesthesia duration, operation duration, intraoperative blood loss, crystalloid and colloid infusion, blood transfusion, urine output, use of Pringle maneuver were statistically different between patients with and without GI complications (P < 0.05). Moreover, patients with GI complications had a more prolonged postoperative parenteral nutrient supporting time, hospital stay and ICU stay, and higher incidence of other complications than those without GI complications (P < 0.05). Multivariate regression indicated that long duration of anesthesia (odds ratio 2.51, P < 0.001) and use of Pringle maneuver (odds ratio 1.37, P ¼ 0.007) were independent risk factors of GI complications after hepatectomy. Conclusions: The incidence of GI complications after hepatectomy is high, which is related to an increase of other complications and a prolonged hospital stay. Avoidance of routinely use of Pringle maneuver and shortening the duration of anesthesia are important measures to reduce the postoperative GI complications.

Background Intestinal ischemia–reperfusion (II/R) is associated with high morbidity and mortality. The aim of this study was to investigate the effects of osthole on lung injury and mortality induced by II/R. Methods A rat model of II/R was induced by clamping the superior mesenteric artery for 90 min followed by reperfusion for 240 min. Osthole was administrated intraperitoneally at 30 min before intestinal ischemia (10 or 50 mg/kg). The survival rate and mean arterial pressure were observed. Blood samples were obtained for blood gas analyses. Lung injury was assessed by the histopathologic changes (hematoxylin and eosin staining), lung wet-to-dry weight ratio, and pulmonary permeability index. The levels of reactive oxygen species, malondialdehyde, interleukin 6, and tumor necrosis factor α, as well as the activities of superoxide dismutase and myeloperoxidase in lung were measured. Results The survival rate, ratio of arterial oxygen tension to fraction of inspired oxygen, and mean arterial pressure decreased significantly after II/R. Results also indicated that II/R-induced severe lung injury evidenced by increase in pathologic scores, lung wet-to-dry weight ratio, and pulmonary permeability index, which was accompanied by increases in the levels of pulmonary reactive oxygen species, malondialdehyde, interleukin 6, tumor necrosis factor α, and the pulmonary myeloperoxidase activity and a decrease in superoxide dismutase activity. Osthole could significantly ameliorate lung injury and improve the previously mentioned variables. Conclusions These findings indicated that osthole could attenuate the lung injury induced by II/R in rats, at least in part, by inhibiting inflammatory response and oxidative stress.

Introduction Sleep disordered breathing (SDB) is a chronic disorder characterized by repeated upper airway collapse during sleep with a high prevalence in patients undergoing cardiac surgery. Although patients with SDB are considered to be at increased risk for postoperative complications after noncardiac surgery, the impact of SDB on postoperative outcomes after cardiac surgery remains obscure. Results Nineteen eligible studies including 3992 patients were identified. SDB was significantly associated with postoperative all-cause mortality (OR 2.44, 95% CI 1.08–5.49), atrial fibrillation (OR 2.15, 95% CI 1.67–2.77), pulmonary complications (OR 2.02, 95% CI 1.20–3.39), acute kidney injury (OR 2.82, 95% CI 1.19–6.66), delirium (OR 6.4, 95% CI 2.6–15.4), and long-term major adverse cardiovascular events (MACE) (OR 3.44, 95% CI 1.43–8.25), but not short-term MACE (OR 1.64, 95% CI 0.57–4.74) or infection (OR 1.50, 95% CI 0.75–3.01). Increasing severity of SDB might be associated with worsened outcomes. Discussion SDB is associated with increased risk of mortality and morbidity after cardiac surgery. Future studies need to explore the optimal screening methods and interventions for SDB in the perioperative period.

Background: This meta-analysis was performed to assess the influence of dexmedetomidine and propofol for adult intensive care unit (ICU) sedation, with respect to patient outcomes and adverse events. Materials and methods: A systematic review was conducted of all randomized controlled trials exploring the clinical benefits of dexmedetomidine versus propofol for sedation in adult intensive care patients. The primary outcomes of this study were length of ICU stay, duration of mechanical ventilation, and risk of ICU mortality. Secondary outcomes included risk of delirium, hypotension, bradycardia and hypertension. Results: Ten randomized controlled trials, involving 1202 patients, were included. Dexmedetomidine significantly reduced the length of ICU stay by

15-F(2t)-isoprostane (IsoP), a marker of reactive oxygen species-induced oxidative stress, is increased after myocardial ischemia and reperfusion. It exerts deleterious effects on postischemic myocardium accompanied with increased release of endothelin-1 (ET-1), a potent vasoconstrictor. We hypothesized that IsoP exacerbates myocardial ischemia-reperfusion injury by stimulating ET-1 production, and that ET-1 blockade can attenuate or prevent these deleterious effects of IsoP.Adult rat hearts were perfused by the Langendorff technique with Krebs-Henseleit solution (KH) at a constant flow rate of 10 mL/min. Global myocardial ischemia was induced by stopping KH perfusion for 40 min followed by 60 min of reperfusion. Hearts were randomized to one of the five groups (n = 8 each): untreated control, treated with IsoP (100 nM), or the ET-1 receptor A/B antagonist bosentan (1 μM) alone or in combination 10 min prior to, during 40 min global ischemia and 15 min of reperfusion, or treated with IsoP as above plus delayed administration of bosentan after 15 min of reperfusion.Coronary effluent ET-1 concentrations in the IsoP group were higher than those in the control group during ischemia and reperfusion (P0.05), which was associated with increased release of cardiac-specific creatine kinase, reduced cardiac contractility during reperfusion, and increased myocardial infarct size (all P0.05 versus control). Bosentan administration during early reperfusion exacerbated the IsoP deleterious effects, while delayed administration attenuated it.15-F(2t)-isoprostane-induced ET-1 production during later reperfusion is detrimental to functional recovery of damaged myocardium, while ET-1 increase during early reperfusion seems to improve it.

Background Intestinal ischemia/reperfusion (I/R) injury is a critical condition associated with high morbidity and mortality. Our previous study showed that ischemic postconditioning (IPo) protects the intestinal mucosa from I/R injury. However, the precise molecular mechanisms of this event remain poorly elucidated. The aim of this study was to investigate the differentially expressed proteins of intestinal mucosa after intestinal I/R with or without IPo, and to explore the potential mechanisms of intestinal I/R injury and the protective effect of IPo in relation to the differential proteins. Materials and Methods Intestinal I/R injury was established by occluding the superior mesenteric artery (SMA) for 60min followed by 60min reperfusion. The rats were randomly allocated into one of three groups based upon the intervention ( n = 8); sham : sham surgical preparation including isolation of the SMA without occlusion was performed; injury: there was no intervention either before or after SMA occlusion; IPo: three cycles of 30 s reperfusion–30 s reocclusion were imposed immediately upon reperfusion. A comparative proteomics approach with two-dimensional gel electrophoresis was used to isolate proteins in intestinal mucosa, the expression of which were regulated by I/R injury post-treated with or without IPo. The differentially displayed proteins were identified through matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS). Results Image analysis revealed that an average of 1300 protein spots were detected on each gel; 16 and 9 proteins showing more than 1.5-fold difference were identified between the Sham versus Injury group and injury group versus IPo group, respectively. The identified proteins were functionally involved in the cellular processes of energy metabolism, anti-oxidation, and anti-apoptosis. Conclusions This study provided new clues for understanding the mechanisms of IPo against intestinal I/R injury.

The emergence of ischaemic post-conditioning (IPO) provides a potential method for experimentally and clinically attenuating various types of organ injuries. There has been little work, however, examining its effects in the setting of lung ischaemia reperfusion (IR). The stress protein, haeme oxygenase-1 (HO-1), has been found to exert a potent, protective role in a variety of lung injury models. In this study, we hypothesised that the induction of HO-1 by IPO plays a protective role against the deleterious effects of IR in the lung.Anaesthetised and mechanically ventilated adult Sprague-Dawley rats were randomly assigned to one of the following groups (n=8 each): the sham-operated control group, the IR group (40 min of left-lung ischaemia and 105 min of reperfusion), the IPO group (three successive cycles of 30-s reperfusion per 30-s occlusion before restoring full perfusion) and the ZnPPIX+IPO group (ZnPPIX, an inhibitor of HO-1, was injected intra-peritoneally at 20 mg kg(-1) 24h prior to the experiment and the rest of the procedures were similar to that of the IPO group). Lung injury was assessed by arterial blood gas analysis, wet-to-dry lung weight ratio and tissue histological changes. The extent of lipid peroxidation was determined by measuring plasma levels of malondialdehyde (MDA) production. Expression of HO-1 was determined by immunohistochemistry.Lung IR resulted in a significant reduction of PaO(2) (data in IR, P0.05 vs. data in sham) and increase of lung wet-to-dry weight ratio, accompanied with increased MDA production and severe lung pathological morphological changes as well as a compensatory increase in HO-1 protein expression, as compared with sham (All P0.05). IPO markedly attenuated all the above pathological changes seen in the IR group and further increased HO-1 expression. Treatment with ZnPPIX abolished all the protective effects of post-conditioning.It may be concluded that IPO protects IR-induced lung injury via induction of HO-1.

Human beta-defensin-2 (BD-2) is a positive ion antimicrobial peptide. We investigated the effects of intestinal ischaemia/reperfusion (II/R) on rat BD-2 mRNA and protein expressions in rat lung to address the potential role of BD-2 in acute lung injury (ALI) induced by II/R.Rats were randomly divided into two groups (n=36 each). (i) Sham control and (ii) II/R group (1h superior mesenteric artery clamping, followed by reperfusion of different durations). In II/R group, 6 animals were sacrificed at 0min, 15min, 30min, 60min, 3h and 6h after reperfusion, and serum, lung tissue and bronchoalveolar lavage fluid were harvested. Samples were taken at the corresponding time points in the sham group. Lung histological changes were observed under microscope and the pulmonary permeability index (PPI) was calculated. The lung tissue levels of TNFalpha were detected by ELISA. BD-2 mRNA and protein expressions were examined by RT-PCR and western blotting techniques, respectively.ALI induced by II/R was confirmed by pathological examination and significantly increased PPI (P0.05 or 0.01). II/R significantly increased the lung TNFalpha levels and upregulated the expressions of BD-2 mRNA and protein expressions (P0.05 or 0.01). BD-2 mRNA expression was significantly positively correlated to the lung TNFalpha level (r=0.823, P0.01) and negatively correlated to PPI (r=-0.615, P0.05).II/R can upregulate BD-2 mRNA and protein expressions in rat lung. BD-2 could be an innate protective factor against II/R-induced lung injury.