Neutrophil extracellular traps aggravate intestinal epithelial necroptosis in ischaemia-reperfusion by regulating TLR4/RIPK3/FUNDC1-required mitophagy.

Neutrophil extracellular trap (NET) has been confirmed to be related to gut barrier injury during intestinal ischaemia-reperfusion (II/R). However, the specific molecular regulatory mechanism of NETs in II/R-induced intestinal barrier damage has yet to be fully elucidated. Here, we reported increased NETs infiltration accompanied by elevated inflammatory cytokines, cellular necroptosis and tight junction disruption in the intestine of human II/R patients. Meanwhile, NETs aggravated Caco-2 intestinal epithelial cell necroptosis, impairing the monolayer barrier in vitro. Moreover, Pad4-deficient mice were used further to validate the role of NETs in II/R-induced intestinal injury. In contrast, NET inhibition via Pad4 deficiency alleviated intestinal inflammation, attenuated cellular necroptosis, improved intestinal permeability, and enhanced tight junction protein expression. Notably, NETs prevented FUN14 domain-containing 1 (FUNDC1)-required mitophagy activation in intestinal epithelial cells, and stimulating mitophagy attenuated NET-associated mitochondrial dysfunction, cellular necroptosis, and intestinal damage. Mechanistically, silencing Toll-like receptor 4 (TLR4) or receptor-interacting protein kinase 3 (RIPK3) via shRNA relieved mitophagy limitation, restored mitochondrial function and reduced NET-induced necroptosis in Caco-2 cells, whereas this protective effect was reversed by TLR4 or RIPK3 overexpression. The regulation of TLR4/RIPK3/FUNDC1-required mitophagy by NETs can potentially induce intestinal epithelium necroptosis.

Neutrophil extracellular traps promote intestinal barrier dysfunction by regulating macrophage polarization during trauma/hemorrhagic shock via the TGF-ß signaling pathway.

The mechanism by which neutrophil extracellular traps (NETs) may cause intestinal barrier dysfunction in response to trauma/hemorrhagic shock (T/HS) remains unclear. In this study, the roles and mechanisms of NETs in macrophage polarization were examined to determine whether this process plays a role in tissue damage associated with T/HS. Rat models of T/HS and macrophage polarization were developed and the levels of NETs formation in the intestinal tissue of T/HS rats were assessed. NET formation was inhibited in models of T/HS to examine the effect on intestinal inflammation and barrier injury. The proportions of pro-inflammatory and anti-inflammatory macrophages in the damaged intestinal tissues were measured. Finally, high-throughput sequencing was performed to investigate the underlying mechanisms involved in this process. The study revealed that the level of NETs formation was increased and that inhibition of NETs formation alleviated the intestinal inflammation and barrier injury. Moreover, the number of pro-inflammatory macrophages increased and the number of anti-inflammatory macrophages decreased. RNA sequencing analysis indicated that NETs formation decreased the expression of transforming growth factor-beta receptor 2 (TGFBR2), bioinformatic analyses revealed that TGFBR2 was significantly enriched in the transforming growth factor-beta (TGF-ß) signaling pathway. Verification experiments showed that NETs impeded macrophage differentiation into the anti-inflammatory/M2 phenotype and inhibited TGFBR2 and TGF-ß expression in macrophages. However, treatment with DNase I and overexpression of TGFBR2, and inhibition of TGF-ß promoted and prevented this process, respectively. NETs may regulate the macrophage polarization process by promoting intestinal barrier dysfunction in T/HS rats through the TGFBR2-mediated TGF-ß signaling pathway.

Neutrophil extracellular traps drive intestinal microvascular endothelial ferroptosis by impairing Fundc1-dependent mitophagy.

Microvascular endothelial damage caused by intestinal ischemia‒reperfusion (II/R) is a primary catalyst for microcirculation dysfunction and enterogenous infection. Previous studies have mainly focused on how neutrophil extracellular traps (NETs) and ferroptosis cause intestinal epithelial injury, and little attention has been given to how NETs, mainly from circulatory neutrophils, affect intestinal endothelial cells during II/R. This study aimed to unravel the mechanisms through which NETs cause intestinal microvascular dysfunction. We first detected heightened local NET infiltration around the intestinal microvasculature, accompanied by increased endothelial cell ferroptosis, resulting in microcirculation dysfunction in both human and animal II/R models. However, the administration of the ferroptosis inhibitor ferrostatin-1 or the inhibition of NETs via neutrophil-specific peptidylarginine deiminase 4 (Pad4) deficiency led to positive outcomes, with reduced intestinal endothelial ferroptosis and microvascular function recovery. Moreover, RNA-seq analysis revealed a significant enrichment of mitophagy- and ferroptosis-related signaling pathways in HUVECs incubated with NETs. Mechanistically, elevated NET formation induced Fundc1 phosphorylation at Tyr18 in intestinal endothelial cells, which led to mitophagy inhibition, mitochondrial quality control imbalance, and excessive mitochondrial ROS generation and lipid peroxidation, resulting in endothelial ferroptosis and microvascular dysfunction. Nevertheless, using the mitophagy activator urolithin A or AAV-Fundc1 transfection could reverse this process and ameliorate microvascular damage. We first demonstrate that increased NETosis could result in intestinal microcirculatory dysfunction and conclude that suppressed NET formation can mitigate intestinal endothelial ferroptosis by improving Fundc1-dependent mitophagy. Targeting NETs could be a promising approach for treating II/R-induced intestinal microcirculatory dysfunction.

Sequential changes in body composition and metabolic response after pancreatic trauma.

OBJECTIVES: Pancreatic trauma and subsequent pancreatic operation result in early pathophysiologic alterations. Understanding changes in energy expenditure and body composition is essential for optimal management. This study aims to observe changes in energy expenditure and body composition in patients during the early postoperative days (PODs) after pancreatic trauma. METHODS: This is a retrospective review of patients who underwent surgery for blunt pancreatic trauma in a single trauma center. Data of body composition by bioimpedance spectroscopy and energy expenditure by indirect calorimetry were collected and analyzed in patients during the early PODs. The association of body composition parameters with major complications was analyzed. RESULTS: Forty-one patients were included. Compared with POD-3, the total body water, extracellular water, fat-free mass, and skeletal muscle mass on POD-7 and -14 decreased significantly (all P < 0.05). The phase angle (PhA) increased significantly from POD-3 to -14 (P < 0.05). Resting energy expenditure was significantly higher than predicted and remained high throughout the study period. Over the 14-d study period, delivered energy was escalated to the level of resting energy expenditure. The PhA was significantly lower in patients with severe morbidity than in those without (3.6 [3.3-4.2] versus 4.5 [4.2-5.0]; P < 0.001). A multivariate analysis found that PhA was the independent variable for severe complications, with an odds ratio of 0.069 (95% CI, 0.011-0.427; P = 0.004). The predictive ability of PhA revealed an area under the receiver operating characteristic curve of 0.837, with an optimal threshold of 4.23. CONCLUSIONS: Changes in body composition and hypermetabolism state were observed from POD-3 to -14 after pancreatic trauma. A postoperative value of PhA < 4.23 is associated with severe complications.

Hesperetin attenuates sepsis-induced intestinal barrier injury by regulating neutrophil extracellular trap formation via the ROS/autophagy signaling pathway.

Background: Hesperetin (HES), one of the major flavonoids that has various biological activities, such as anti-inflammatory and antioxidant activities, may preserve the intestinal barrier during sepsis. However, the detailed mechanism remains unclear. Our previous studies confirmed that neutrophil extracellular traps (NETs) may jeopardize the intestinal barrier via a reactive oxygen species (ROS)-dependent pathway during sepsis. Therefore, we hypothesized that HES may inhibit NET formation and protect the intestinal barrier function during sepsis. Methods: Mice were pretreated with HES (50 mg kg-1) intraperitoneally for one week, and sepsis models were then induced using lipopolysaccharides (LPS) (10 mg kg-1). The mice were randomly divided into three groups: (1) sham group; (2) LPS group; and (3) HES + LPS group. Twenty-four hours after LPS injection, the serum and terminal ileum specimens were collected for subsequent studies. To detect ROS production and NET formation in vitro, human neutrophils were collected and incubated with phorbol-12-myristate-13-acetate (PMA) and various concentrations of HES. The level of autophagy was measured by an immunofluorescence assay and western blot analysis. TUNEL staining was utilized to analyze cell apoptosis. Results: The outcomes demonstrated that HES decreased inflammatory cytokine and myeloperoxidase (MPO) levels in serum and attenuated distant organ dysfunction in LPS-induced septic mice. Meanwhile, HES treatment reversed intestinal histopathological damage in septic mice, improving intestinal permeability and enhancing tight junction expression. Moreover, we found that neutrophil infiltration and NET formation in the intestine were suppressed during sepsis after HES pretreatment. In vitro, HES treatment reduced PMA-induced ROS production and NET formation, which were reversed by hydrogen peroxide (H2O2) administration. Notably, HES also inhibited NET formation by reducing the microtubule-associated protein light chain 3 (LC3)-II/LC3-I ratio (an indicator of autophagy) in PMA-induced neutrophils, which was reversed by rapamycin. Moreover, when autophagy was suppressed by chloroquine or induced by rapamycin, apoptosis in cells will be switched with autophagy. Conclusion: Taken together, these findings suggest that HES may inhibit NET formation in a ROS/autophagy-dependent manner and switch neutrophil death from NETosis to apoptosis, which reduced NETs-related intestinal barrier damage, providing a novel protective role in intestinal barrier dysfunction during sepsis.

Persistent fibrinolysis shutdown is associated with increased mortality in traumatic pancreatic injury.

PURPOSE: The features of fibrinolytic system modifications and their relationship with prognosis are still unknown in traumatic pancreatic injury. The object of this prospective cohort research was to identify fibrinolytic characteristics in patients with pancreatic trauma and to identify the correlation to mortality. METHOD: A prospective screening of traumatic pancreatic injury patients was done for five years. The fibrinolytic status of patients was determined by thromboelastography (TEG). The percentage reduction in clot strength 30 min (LY30) after the time of maximal clot strength was utilized to distinguish the fibrinolytic phenotype of individuals, including fibrinolytic shutdown (SD), physiologic fibrinolysis (PHYS) and hyperfibrinolysis (HF). Two cohorts, transient fibrinolytic shutdown (TSD) and persistent fibrinolytic shutdown (PSD), were divided according to whether fibrinolytic shutdown persisted within one week. Demographics, injury severity, characteristics of pancreatic injury, treatment, and outcomes were compared. RESULT: A total of 180 cases enrolled, aged 42(interquartile range 32-51) years, 88% males, 97% were blunt trauma. The median ISS was 19(IQR 10-25), and 76% were AAST grade III to V (high-grade). At admission, there were 159 cases of SD (88%), 15 cases of PHYS (8%) while 6 cases of HF (3%). Of these, the TSD cohort included 54 patients (34%), while the PSD cohort included 105 patients (66%). Compared with the TSD cohort, the PSD cohort had more severe injury (ISS 21[IQR 12-27] vs 16[IQR 9-22], p = 0.006) and a higher proportion of AAST high-grade (83% vs 67%, p = 0.035). Persistent fibrinolytic shutdown was associated with operative treatment (odds ratio [OR] 3.111; 95%CI 1.146-8.447; p = 0.026), associated intra-abdominal injury (OR 8.331; 95% CI 1.301-53.336; p = 0.025) and admission LY30 (OR 0.016; 95% CI 0.002 - 0.120; p < 0.001). It was an independent predictor of mortality (adjusted odds ratio [AOR] 4.674; 95% CI 1.03 to 21.14; p = 0.045). CONCLUSION: Fibrinolytic shutdown especially persistence of this phenotype is more common in traumatic pancreatic injury than PHYS and HF, which related with mortality. Risk factors including LY30 at admission, intra-abdominal injury and operative treatment were associated with the persistent fibrinolytic shutdown. Sheltered the patients from these risk factors seems to be beneficial, which need to be confirmed by further large-scale studies.

Lightweight ZnO/Carbonated Cotton Fiber Nanocomposites for Electromagnetic Interference Applications: Preparation and Properties.

Electromagnetic wave pollution has become a significant harm posed to human health and precision instruments. To shelter such instruments from electromagnetic radiation, high-frequency electromagnetic interference (EMI) shielding materials are extremely desirable. The focus of this research is lightweight, high-absorption EMI shielding composites. Simple aqueous dispersion and drying procedures were used to prepare cotton fiber (CF)-based sheets combined with various zinc oxide (ZnO) contents. These composites were carbonated in a high-temperature furnace at 800 °C for two hours. The obtained CF/ZnO samples have densities of 1.02-1.08 g/cm3. The EMI shielding effectiveness of CF-30% ZnO, CF-50% ZnO, and CF-70% ZnO reached 32.06, 38.08, and 34.69 dB, respectively, to which more than 80% of absorption is attributed. The synergetic effects of carbon networks and surface structures are responsible for the high EMI shielding performance; various reflections inside the interconnected networks may also help in improving their EMI shielding performance.

Urban-Rural Distinction or Economic Segmentation: A Study on Fear and Inferiority in Poor Children's Peer Relationships.

Peer relationships play an important role in the growth of children. This study offers insights about feelings of fear and inferiority in children's peer relationships. Based on a national survey, the 2018 Construction for Social Policy Support System for Urban and Rural Poor Families in China, initiated by the Ministry of Civil Affairs, and using multiple regression models and a structural equation model, this study discusses whether and how having a rural household registration or being from a poor (dibao) family has an isolation effect on fear and inferiority in children's peer relationships. The research findings indicate that children with a rural household registration or those from a dibao family are at a disadvantage in peer interactions. Moreover, rural resident identity has an indirect effect on children's fear of peers and inferiority, mainly through psychological resilience, anxiety and depression, and mobile phone dependence. Being from a dibao family directly influences children's fear and inferiority in their peer relationships; it also indirectly influences fear of peers and inferiority through psychological resilience. This study suggests that more attention should be paid to fear of peers and inferiority in rural children or children from a dibao family.

Nuclear Radiation Knowledge and Anxiety Levels among Residents around a Nuclear Power Plant in Liaoning Province, China.

ABSTRACT: Awareness of radiation-related knowledge (RRK) and nuclear energy-related knowledge (NERK) among residents around a nuclear power plant (NPP), as well as their concerns about a NPP, were investigated. A face-to-face survey was conducted among 1,775 residents within 30 km around the NPP in Liaoning Province, China. A single-item Likert scale, Spearman's/Pearson's correlation coefficients, Student's t-test, ANOVA, and multiple-linear regression analysis were employed. Awareness of RRK and NERK among residents around the NPP was 27.7% and 36.6%, respectively. The anxiety level of respondents was negatively corelated with the distance from their residence to the NPP and age. Also, 55.6% of respondents thought that the publicity about nuclear energy/NPPs was insufficient, and 82.7% of respondents wanted to know relevant information about NPPs. Awareness of RRK and NERK among residents around the NPP was relatively low, which was related to education, occupation, and income. The anxiety level among residents was related to distance and age. The public was eager to know about RRK and NERK. These findings indicate that the publicity and education of RRK and NERK among residents around the NPP should be strengthened.

Neutrophil extracellular trap formation index predicts occurrences of deep surgical site infection after laparotomy.

BACKGROUND: Deep surgical site infections (DSSIs) are serious complications after laparotomy. Neutrophil extracellular traps (NETs) play a vital role in the development of DSSI. Here, we focused on a new approach to predicting the occurrence of DSSI through the detection of the NET formation index (NFI), and compared its prediction ability with other clinical infection indicators. METHODS: Patients who received laparotomy were prospectively enrolled in this study. General information, APACHE II score, SOFA score, and serum infection indicators were recorded. The postoperative abdominal drainage fluid was collected within 3 days after the operation for quantification of the NFI. RESULTS: A total of 92 consecutive patients were included, with 22 patients were diagnosed with DSSI. The NFI in the DSSI group was 32.70%±19.33% while the corresponding index was 10.70%±8.25% in the non-DSSI group (P<0.01). The mean APACHE II and SOFA score had significant differences between the two groups. The NFI was positively correlated with the APACHE II score (P<0.01, r=0.269) and SOFA score (P=0.013, r=0.258). Patients with a high NFI (NFI >13.86%) had a higher risk of developing DSSI. According to the receiver operating characteristic (ROC) curve, the area under the ROC curve (AUC) of the NFI, C-reactive protein (CRP) and procalcitonin (PCT) were 0.912, 0.748 and 0.731, respectively. CONCLUSIONS: In this cohort of surgical patients, the quantification of the NFI had a considerable predictive value for early identification of DSSI. The NFI in drainage fluid turned out to be a more sensitive and specific predictor of DSSI than serum infection indicators including CRP and PCT.

Bioelectrical impedance analysis-guided fluid management promotes primary fascial closure after open abdomen: a randomized controlled trial.

BACKGROUND: Fluid overload (FO) after resuscitation is frequent and contributes to adverse outcomes among postinjury open abdomen (OA) patients. Bioelectrical impedance analysis (BIA) is a promising tool for monitoring fluid status and FO. Therefore, we sought to investigate the efficacy of BIA-directed fluid resuscitation among OA patients. METHODS: A pragmatic, prospective, randomized, observer-blind, single-center trial was performed for all trauma patients requiring OA between January 2013 and December 2017 to a national referral center. A total of 140 postinjury OA patients were randomly assigned in a 1:1 ratio to receive either a BIA-directed fluid resuscitation (BIA) protocol that included fluid administration with monitoring of hemodynamic parameters and different degrees of interventions to achieve a negative fluid balance targeting the hydration level (HL) measured by BIA or a traditional fluid resuscitation (TRD) in which clinicians determined the fluid resuscitation regimen according to traditional parameters during 30 days of ICU management. The primary outcome was the 30-day primary fascial closure (PFC) rate. The secondary outcomes included the time to PFC, postoperative 7-day cumulative fluid balance (CFB) and adverse events within 30 days after OA. The Kaplan-Meier method and the log-rank test were utilized for PFC after OA. A generalized linear regression model for the time to PFC and CFB was built. RESULTS: A total of 134 patients completed the trial (BIA, n = 66; TRD, n = 68). The BIA patients were significantly more likely to achieve PFC than the TRD patients (83.33% vs. 55.88%, P < 0.001). In the BIA group, the time to PFC occurred earlier than that of the TRD group by an average of 3.66 days (P < 0.001). Additionally, the BIA group showed a lower postoperative 7-day CFB by an average of 6632.80 ml (P < 0.001) and fewer complications. CONCLUSION: Among postinjury OA patients in the ICU, the use of BIA-guided fluid resuscitation resulted in a higher PFC rate and fewer severe complications than the traditional fluid resuscitation strategy.

Protective effect of ethyl pyruvate on gut barrier function through regulations of ROS-related NETs formation during sepsis.

BACKGROUND: Sepsis impairs the function of the intestinal barrier through neutrophil extracellular traps (NETs). Reactive oxygen species (ROS)-induced activation of mitogen-activated protein kinase (MAPK) is involved in NET formation. Ethyl pyruvate (EP), a potent and effective ROS scavenger, ameliorates sepsis-associated intestinal barrier dysfunction, but the detailed mechanism is unknown. The current study aimed to explore the eff ;ects of EP on sepsis-induced intestinal barrier dysfunction and whether ROS and NETs were involved. METHODS: A sepsis model was induced in mice by intraperitoneal injection of LPS (10 mg/kg). The mice were divided into 4 groups: (1) sham group; (2) LPS group; (3) DNase-1 + LPS group; and (4) EP + LPS group. EP or DNase-1 was intraperitoneally injected after the LPS model was established. After 24 h, the small intestine and blood were collected for analysis. Human neutrophils were harvested and incubated with phorbol-12-myristate-13-acetate (PMA) or PMA + EP, and ROS and NET generation was measured. RESULTS: EP significantly decreased proinflammatory cytokines and MPO-DNA in the LPS model. In addition, EP suppressed NET formation in the intestines of endotoxemic mice. The decrease in NETs induced by EP or DNase-1 alleviated histopathological damage, intestinal cell apoptosis and increased tight junction expression. In vitro, the treatment of EP abolished PMA-induced ROS production and NET formation which could be reversed by H2O2 treatment. Meanwhile, EP also abolished MAPK ERK1/2 and p38 activation during PMA-induced NET formation. CONCLUSION: This study was the first to demonstrate that EP alleviated NET formation and sepsis-induced intestinal damage through blockage of ROS mediated MAPK ERK1/2 and p38 activation.

Predictors of irreversible intestinal resection in patients with acute mesenteric venous thrombosis.

BACKGROUND: Acute mesenteric venous thrombosis (AMVT) can cause a poor prognosis. Prompt transcatheter thrombolysis (TT) can achieve early mesenteric revascularization. However, irreversible intestinal ischemia still occurs and the mechanism is still unclear. AIM: To evaluate the clinical outcomes of and to identify predictive factors for irreversible intestinal ischemia requiring surgical resection in AMVT patients treated by TT. METHODS: The records of consecutive patients with AMVT treated by TT from January 2010 to October 2017 were retrospectively analyzed. We compared patients who required resection of irreversible intestinal ischemia to patients who did not require. RESULTS: Among 58 patients, prompt TT was carried out 28.5 h after admission. A total of 42 (72.4%) patients underwent arteriovenous combined thrombolysis, and 16 (27.6%) underwent arterial thrombolysis alone. The overall 30-d mortality rate was 8.6%. Irreversible intestinal ischemia was indicated in 32 (55.2%) patients, who had a higher 30-d mortality and a longer in-hospital stay than patients without resection. The significant independent predictors of irreversible intestinal ischemia were Acute Physiology and Chronic Health Evaluation (APACHE) II score (odds ratio = 2.368, 95% confidence interval: 1.047-5.357, P = 0.038) and leukocytosis (odds ratio = 2.058, 95% confidence interval: 1.085-3.903, P = 0.027). Using the receiver operating characteristic curve, the cutoff values of the APACHE II score and leukocytosis for predicting the onset of irreversible intestinal ischemia were calculated to be 8.5 and 12 × 109/L, respectively. CONCLUSION: Prompt TT could achieve a favorable outcome in AMVT patients. High APACHE II score and leukocytosis can significantly predict the occurrence of irreversible intestinal ischemia. Therefore, close monitoring of these factors may help with the early identification of patients with irreversible intestinal ischemia, in whom ultimately surgical resection is required, before the initiation of TT.

Early intravenous administration of tranexamic acid ameliorates intestinal barrier injury induced by neutrophil extracellular traps in a rat model of trauma/hemorrhagic shock.

BACKGROUND: Early intravenous administration of tranexamic acid has been shown to protect the intestinal barrier after a model of trauma-hemorrhagic shock in the rat, but the potential mechanism remains unclear. Our previous studies have demonstrated that neutrophil extracellular traps contribute to the intestinal barrier dysfunction during sepsis and other critical conditions. Meanwhile, there are high levels of neutrophil infiltration in the intestine during trauma-hemorrhagic shock. Here, we hypothesized that neutrophil extracellular trap formation played a vital role during trauma-hemorrhagic shock-induced intestinal injury and that tranexamic acid, a serine protease inhibitor, may inhibit neutrophil extracellular trap formation and protect intestinal barrier function in trauma-hemorrhagic shock. METHODS: A model of trauma-hemorrhagic shock in male rats was established. The rats were divided into 6 groups: (1) sham group; (2) trauma-hemorrhagic shock group; (3) trauma-hemorrhagic shock + DNase I group; (4) trauma-hemorrhagic shock + tranexamic acid group; (5) trauma-hemorrhagic shock + tranexamic acid (different time) group; and (6) trauma-hemorrhagic shock + tranexamic acid (different doses) group. The DNase I solution was injected intravenously to disrupt neutrophil extracellular traps immediately after the trauma-hemorrhagic shock model was completed. After 24 hours, the small intestine and blood were collected for analysis. Human neutrophils were harvested and incubated with phorbol-12-myristate-13-acetate or tranexamic acid, generation of reactive oxygen species, and key proteins expression were detected. RESULTS: Trauma-hemorrhagic shock induced the formation of intestinal neutrophil extracellular traps and disrupted the intestinal tight junction proteins. Clearing of neutrophil extracellular traps by DNase I resulted in increased expression of tight junction proteins and alleviated the intestinal injury. Early intravenous tranexamic acid administration (1 hour after trauma-hemorrhagic shock) decreased neutrophil extracellular trap formation and prevented tight junction protein disruption compared to the non-tranexamic acid group; however, after delayed administration of tranexamic acid (6 hours), there were no changes in neutrophil extracellular trap formation and intestinal injuries compared to the non-tranexamic acid group. Furthermore, tranexamic acid inhibited neutrophil extracellular trap formation and protected the intestinal barrier in a dose-dependent manner and high-dose (20 mg/kg) treatment of tranexamic acid showed a better effect compared with the therapeutic dose (10 mg/kg). The results of thromboelastography demonstrated that the R and K values in the high-dose group decreased (R, 1.85 ± 0.14 vs 3.87 ± 0.16 minutes, P < .001; K, 0.95 ± 0.04 vs 1.48 ± 0.07 minutes, P < .001), accompanied by a decrease in LY30, indicating that treatment with a high dose of tranexamic acid may cause hypercoagulability and shutdown of fibrinolysis. In addition, less neutrophil extracellular trap formation was detected in neutrophils incubated with neutrophils via an reactive oxygen species-dependent pathway. CONCLUSION: We first demonstrated a novel role of neutrophil extracellular traps in the pathophysiology of intestinal barrier dysfunction during trauma-hemorrhagic shock. Notably, early but not delayed intravenous administration of tranexamic acid effectively inhibits neutrophil extracellular trap formation and protects intestinal barrier function. Therefore, these results suggested a potential theoretic intervention for the protection of the intestinal barrier during trauma-hemorrhagic shock. In such a process, tranexamic acid appears to regulate neutrophil extracellular trap formation via the classic reactive oxygen species/mitogen-activated protein kinase pathway.

Outcomes and clinical characteristics of transmural intestinal necrosis in acute mesenteric ischemia.

Background: Acute mesenteric ischemia (AMI) is a rare life-threatening condition, especially for the patients with transmural intestinal necrosis (TIN). However, the optimal time for surgical intervention is controversial. As a series study, this study aimed to identify the outcomes and clinical characteristic of patients with TIN. Methods: Clinical data of 158 patients with AMI from January 2010 to December 2017 were retrospectively analyzed in a national gastrointestinal referral center in China to confirm the outcomes and identify predictors for TIN. Results: According to the results of pathological assessment and follow-up, 62 patients were TIN and 96 were non-TIN. Patients with TIN have a higher mortality and incidence of severe complications. The significant independent predictors for TIN were arterial lactate level (OR: 4.76 [2.29 ∼ 9.89]), free intraperitoneal fluid (OR: 9.49 [2.56 ∼ 35.24]) and pneumatosis intestinalis (OR: 7.08 [1.68 ∼ 29.82]) in computed tomography (CT) scan imaging. The overall area under the receiver operating characteristics (ROC) curve of the model was 0.934 (95% confidence interval: 0.893 ∼ 0.974). Using ROC curve, the cutoff value of arterial lactate level predicting the onset of TIN was 2.65 mmol/L. Conclusions: Patients concomitant with TIN manifest a higher risk of poor prognosis. The three predictors for TIN were arterial lactate level >2.65 mmol/L, free intraperitoneal fluid and pneumatosis intestinalis. Close monitoring these predictors would help identify AMI patients developed TIN and in urgent need for bowel resection.

Endovascular stent placement for isolated superior mesenteric artery dissection with intestinal ischaemia.

BACKGROUND: Isolated superior mesenteric artery dissection (ISMAD) is rare, especially when associated with intestinal ischaemia. We report our clinical experience managing this condition. PATIENTS AND METHODS: Medical records from 22 patients with ISMAD and intestinal ischaemia were retrospectively analysed. Conservative treatment was given to all patients as first line therapy. Subsequently, 15 patients received endovascular stent placement and three patients received endovascular stent placement plus intestinal resection and anastomosis. RESULTS: After conservative treatment, the symptoms of three patients were remarkably relieved; however, a repeat contrast CT showed that stenosis was aggravated. Hence, endovascular stent placement was performed in all 15 patients. Enteral nutrition was successfully restored in 12 patients. Three patients showed signs of chronic intestinal ischaemia, including peritonitis and ileus. These patients underwent intestinal resection and anastomosis. Enteral nutrition was restored at postoperative week two. No signs of intestinal ischaemia recurred during two-years of follow-up. CONCLUSIONS: We recommend endovascular stent placement as a feasible, effective, and minimally invasive procedure in patients with ISMAD and symptoms of intestinal ischaemia.

DNase-1 Treatment Exerts Protective Effects in a Rat Model of Intestinal Ischemia-Reperfusion Injury.

A growing number of studies have recently revealed a potential role for neutrophil extracellular traps (NETs) in the development of inflammation, coagulation and cell death. Deleterious consequences of NETs have been identified in ischemia-reperfusion (I/R)-induced organ damage, thrombosis and sepsis. And exogenous DNase-I has been suggested as a therapeutic strategy to attenuate ischemia-reperfusion (I/R) injuries in the kidney, brain and myocardium. Herein, we designed a study to investigate whether NETs contribute to the pathogenesis of intestinal I/R injury and evaluated the therapeutic value of DNase-1 in a rat model of intestinal I/R injury. In this rat model of intestinal I/R injury, we found that extracellular DNA was readily detectable in rat serum after 1 h of ischemia and 2 h of reperfusion. Treatment with DNase-1 significantly reduced the inflammatory response, restored intestinal barrier integrity and increased the expression of tight junction proteins. Our results indicate the existence of NETs in I/R-challenged intestinal tissues and firstly provide more evidence that DNase-1 may be an effective treatment for attenuating intestinal I/R injury.

A new species of Orientatractis (Nematoda: Atractidae) from the tortoise Indotestudo elongata (Blyth) in China.

A new species of nematode, Orientatractis longicaudata n. sp. is described from the intestine of Indotestudo elongata (Blyth) (Testudinidae) from Zoo of Tianjin, Tianjin, China. The new species can be easily distinguished from its congers by having longer tail, by the length of gubernaculum and left spicule, and by the numbers of caudal papillae. This is first species of Orientatractis Petter, 1966 reported in China. A key to the species of Orientatractis is provided.

Open Abdomen Improves Survival in Patients With Peritonitis Secondary to Acute Superior Mesenteric Artery Occlusion.

BACKGROUND: Damage control surgery and open abdomen (OA) have been extensively used in the severe traumatic patients. However, there was little information when extended to a nontrauma setting. The purpose of this study was to evaluate whether the liberal use of OA as a damage control surgery adjunct improved the clinical outcome in acute superior mesenteric artery occlusion patients. STUDY DESIGN: A single-center, retrospective cohort review was performed in a national tertiary surgical referral center. RESULTS: Forty-four patients received OA (OA group) and 65 patients had a primary fascial closure (non-OA group) after diagnosed as peritonitis secondary to acute superior mesenteric artery occlusion from January, 2005 to June, 2016. Revascularization was achieved through endovascular aspiration embolectomy, open embolectomy, or percutaneous stent. No difference of bowel resection length was found between groups in the first emergency surgery. However, more non-OA patients (35.4%) required a second-look enterectomy to remove the residual bowel ischemia than OA patients (13.6%, P<0.05). OA was closed within a median of 7 days (4 to 15 d). There was a mean of 134 cm residual alive bowel in OA, whereas 96 cm in non-OA. More non-OA patients suffered from intra-abdominal sepsis (23.1% vs. 6.8%, P<0.01), intra-abdominal hypertension (31% vs. 0, P<0.01), and acute renal failure (53.8% vs. 31.8%, P<0.05) than OA group after surgery. Short-bowel syndrome occurred infrequently in OA than non-OA patients (9.1% vs. 36.9%, P<0.01). OA significantly decreased the 30-day (27.3% vs. 52.3%, P<0.01) and 1-year mortality rate (31.8 % vs. 61.5%, P<0.01) compared with non-OA group. CONCLUSIONS: Liberal use of OA, as a damage control adjunct avoided the development of intra-abdominal hypertension, reduced sepsis-related complication, and improved the clinical outcomes in peritonitis secondary to acute SMA occlusion.

Systemic and Splanchnic Lipopolysaccharide and Endothelin-1 Plasma Levels in Liver Cirrhosis before and after Transjugular Intrahepatic Portosystemic Shunt.

Lipopolysaccharide (LPS) and endothelin- (ET-) 1 may aggravate portal hypertension by increasing intrahepatic resistance and splanchnic blood flow. In the portal vein, after TIPS shunting, LPS and ET-1 were significantly decreased. Our study suggests that TIPS can benefit cirrhotic patients not only in high hemodynamics related variceal bleeding but also in intestinal bacterial translocation associated complications such as endotoxemia.