Intestinal ischemia-reperfusion of macaques triggers a strong innate immune response

AIM: To investigate inflammatory injury in the intestinal mucosa after intestinal ischemia-reperfusion (IIR) with Toll-like receptor (TLR)-mediated innate immunity. METHODS: Ten macaques were randomized into control and IIR groups. The distribution and expression level of TLR2, TLR4, MD2, nuclear factor (NF)-kappa B p65 and interferon (IFN)-gamma were measured by immunohistochemical stain and western blotting. The mRNA expression of TLR4, TLR2, MD2, interleukin (IL)-1 beta and tumor necrosis factor (TNF)-alpha were measured by reverse transcriptase-polymerase chain reaction. The cytokine levels in blood and intestinal tissues were measured by ELISA. RESULTS: Obvious hemorrhage and erosion of mucosae were seen in the IIR group. Expression of TLR2, TLR4, MD2, NF-kappa B p65 and IFN-gamma. was significantly higher in the IIR group than in the control group (0.13 +/- 0.04, 0.22 +/- 0.04, 0.16 +/- 0.06, 0.65 +/- 0.12, 0.38 +/- 0.10 vs 0.07 +/- 0.04, 0.08 +/- 0.03, 0.04 +/- 0.02, 0.19 +/- 0.06, 0.14 +/- 0.05, P < 0.05). In addition, the expression of TLR2, TLR4, MD2, IL-1 beta and TNF-alpha mRNA in the IIR group were significantly higher than those of control group(1.52 +/- 0.15, 1.39 +/- 0.06, 1.94 +/- 0.12, 1.48 +/- 0.15, 0.66 +/- 0.08 vs 0.31 +/- 0.05, 0.5 +/- 0.04, 0.77 +/- 0.05, 0.35 +/- 0.08, 0.18 +/- 0.04, P < 0.05). Furthermore, IL-1 beta, IL-6 and TNF-alpha levels in the macaques ileum and plasma were significantly higher than in the control group (plasma: 86.3 +/- 15.2, 1129 +/- 248.3, 77.8 +/- 16.2 vs 29.5 +/- 7.3, 19.8 +/- 8.2, 5.6 +/- 1.7; ileum: 273.4. +/- 44.7, 1636 +/- 168.0, 205.5 +/- 30.7 vs 76.8 +/- 20.5, 663.4 +/- 186.9, 49.0 +/- 9.4; P < 0.05). CONCLUSION: After IIR, general inflammatory injury in the intestinal mucosa is correlated with a strong innate immune response, mediated by activation of the TLR-NF-kappa B-cytokine pathway. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

Effect of nuclear factor kappa B on intercellular adhesion molecule-1 expression and neutrophil infiltration in lung injury induced by intestinal ischemia/reperfusion in rats

AIM： To investigate the role of nuclear factor kappa B （NF-κB） in the pathogenesis of lung injury induced by intestinal ischemia/reperfusion （I/R）, and its effect on intercellular adhesion molecule-1 （ICAM-1） expression and neutrophil infiltration. METHODS： Twenty-four Wistar rats were divided randomly into control, I/R and pyrrolidine dithiocarbamate （PDTC） treatment groups, n = 8 in each. I/R group and PDTC treatment group received superior mysenteric artery （SMA） occluding for 1 h and reperfusion for 2 h. PDTC group was administrated with intraperitoneal injection of 2% 100 mg/kg PDTC 1 h before surgery. Lung histology and bronchia alveolus lung fluid （BALF） protein were assayed. Serum IL-6, lung malondialdehyde （MDA） and myeloperoxidase （MPO） as well as the expression level of NF-κB and ICAM-1 were measured.RESULTS： Lung injury induced by intestinal I/R, was characterized by edema, hemorrhage and neutrophil infiltration as well as by the significant rising of BALF protein. Compared to control group, the levels of serum IL-6 and lung MDA and MPO increased significantly in I/R group （P=0.001）. Strong positive expression of NF-κB p65 and ICAM-1 was observed. After the administration of PDTC, the level of serum IL-6, lung MDA and MPO as well as NF-κB and ICAM-1 decreased significantly （P〈 0.05） when compared to I/R group.CONCLUSION： The activation of NF-κB plays an important role in the pathogenesis of lung injury induced by intestinal I/R through upregulating the neutrophil infiltration and lung ICAM-1 expression. PDTC as an inhibitor of NF-κB can prevent lung injury induced by intestinal I/R through inhibiting the activity of NF-κB.

Protective effect of pyrrolidine dithiocarbamate on liver injury induced by intestinal ischemia-reperfusion in rats

BACKGROUND: The nuclear translocation of transcription factors may be a critical factor in the intracellular pathway involved in ischemia/reperfusion(I/R) injury. The aim of the study was to evaluate the role of nuclear factor-kappa B (NF-κB) in the pathogenesis of liver injury induced by intestinal ischemia/reperfusion (IIR) and to investigate the effect of pyrrolidine dithiocarbamate (PDTC) on this liver injury. METHODS: Male Wistar rats were divided randomly into three experimental groups (8 rats in each): sham operation group (control group); intestinal/reperfusion group(I/R group): animals received 1-hour of intestinal ischemia and 2-hour reperfusion; and PDTC treatment group (PDTC group): animals that received I/R subject to PDTC treatment (100 mg/kg). The histological changes in the liver and intestine were observed, and the serum levels of tumor necrosis factor-α (TNF-α), alanine aminotransferase (ALT), aspartate aminotransferase (AST), liver superoxide dismutase (SOD), and nitrite/nitrate (NO) were measured. The immunohistochemical expression and Western blot analysis of liver NF-κB and intercellular adhesion molecule-1(ICAM-1) were observed. RESULTS: IIR induced liver injury characterized by the histological changes of liver edema, hemorrhage, polymorphonuclear neutrophil (PMN) infiltration, and elevated serum levels of AST and ALT. The serum TNF-α level was significantly higher than that of the control group(P<0.01) and a high level of liver oxidant product was observed (P<0.01). These changes were parallel to the positive expression of NF-κB and ICAM-1. After the administration of PDTC, the histological changes after liver injury were improved; the levels of SOD and NO in the liver were elevated and reduced, respectively (P<0.01). The expressions of ICAM-1 and NF-κB in the liver were weakened (P<0.01). CONCLUSION: NF-κB plays an important role in the pathogenesis of liver injury induced by HR. PDTC, an agent known to inhibit the activation of NF-κB, can reduce and prevent this injury.

Alcohol dehydrogenase: A potential new marker for diagnosis of intestinal ischemia using rat as a model

AIM: Intestinal ischemia (Ii) is an abdominal emergency due to blockade of the superior mesenteric artery resulting in 60-100% mortality if diagnosed late. Changes in several biochemical parameters such as D (-)-lactate, Creatinine kinase isoenzymes and lactate dehydrogenase suggested for early diagnosis, lack specificity and sensitivity. Therefore a biochemical parameter with greater sensitivity needs to be identified. METHODS: Wistar male rats were randomly assigned into two groups; control sham operated (n = 24) and ischemic test (n = 24) group. Superior mesenteric arterial occlusion was performed in the ischemic test group for 1 h. Alcohol dehydrogenase (ADH) was estimated in blood from portal vein, right ventricle of heart, dorsal aorta (DA) and inferior vena cava (IVC). The Serum glutamic acid pyruvate transaminase (SGPT) was also estimated in blood from portal vein and right ventricle of heart. RESULTS: A significant increase (P<0.001) in the levels of ADH in both portal blood as well as heart blood of the test group (232.72±99.45 EU and 250.85±95.14 EU, respectively) as compared to the control group (46.39±21.69 EU and 65.389±30.55 EU, respectively) were observed. Similarly, increased levels of ADH were observed in blood samples withdrawn from DA and IVC in test animals (319.52±80.14 EU and 363.90±120.68 EU, respectively) as compared to the control group (67.68±63.22 EU and 72.50±58.45 EU, respectively). However, in test animals there was significant increase in SGPT in portal blood (P= 0.054) without much increase in heart blood. CONCLUSION: Significant increase in the levels of ADH in portal and heart blood within 1 h of SMA occlusion without increase in SGPT in heart blood, suggests that the origin of ADH is from ischemic intestine and not from liver. Similarly, raised ADH levels were found in DA and IVC as well. IVC blood does represent peripheral blood sample. A raised level of ADH in test animals confirms it to be a potential marker in the early diagnosis of li.

Recombinant angiopoietin-like protein 4 attenuates intestinal barrier structure and function injury after ischemia/reperfusion

BACKGROUND Intestinal barrier breakdown,a frequent complication of intestinal ischemiareperfusion(I/R)including dysfunction and the structure changes of the intestine,is characterized by a loss of tight junction and enhanced permeability of the intestinal barrier and increased mortality.To develop effective and novel therapeutics is important for the improvement of outcome of patients with intestinal barrier deterioration.Recombinant human angiopoietin-like protein 4(rhANGPTL4)is reported to protect the blood-brain barrier when administered exogenously,and endogenous ANGPTL4 deficiency deteriorates radiationinduced intestinal injury.AIM To identify whether rhANGPTL4 may protect intestinal barrier breakdown induced by I/R.METHODS Intestinal I/R injury was elicited through clamping the superior mesenteric artery for 60 min followed by 240 min reperfusion.Intestinal epithelial(Caco-2)cells and human umbilical vein endothelial cells were challenged by hypoxia/reoxygenation to mimic I/R in vitro.RESULTS Indicators including fluorescein isothiocyanate-conjugated dextran(4 kilodaltons;FD-4)clearance,ratio of phosphorylated myosin light chain/total myosin light chain,myosin light chain kinase and loss of zonula occludens-1,claudin-2 and VE-cadherin were significantly increased after intestinal I/R or cell hypoxia/reoxygenation.rhANGPTL4 treatment significantly reversed these indicators,which were associated with inhibiting the inflammatory and oxidative cascade,excessive activation of cellular autophagy and apoptosis and improvement of survival rate.Similar results were observed in vitro when cells were challenged by hypoxia/reoxygenation,whereas rhANGPTL4 reversed the indicators close to normal level in Caco-2 cells and human umbilical vein endothelial cells significantly.CONCLUSION rhANGPTL4 can function as a protective agent against intestinal injury induced by intestinal I/R and improve survival via maintenance of intestinal barrier structure and functions.

Protective effects of terminal ileostomy against bacterial translocation in a rat model of intestinal ischemia/reperfusion injury

AIM: To investigate the effects of terminal ileostomy on bacterial translocation (BT) and systemic inflammation after intestinal ischemia/reperfusion (I/R) injury in rats.

Comparison of the chloride channel activator lubiprostone and the oral laxative Polyethylene Glycol 3350 on mucosal barrier repair in ischemic-injured porcine intestine

AIM： To investigate the effects of lubiprostone and Polyethylene Glycol 3350 （PEG） on mucosal barrier repair in ischernic-injured porcine intestine. METHODS： Ileum from 6 piglets （approximately 15 kg body weight） was subjected to ischemic conditions by occluding the local rnesenteric circulation for 45 min in vivo. Ileal tissues from each pig were then harvested and mounted in Ussing chambers and bathed in oxygenated Ringer＇s solution in vitro. Intestinal barrier function was assessed by measuring transepithelial electrical resistance （TER） and mucosal-to-serosal fluxes of ^3H-rnannitol and ^14C-inulin. Statistical analyses of data collected over a 120-min time course included 2-way ANOVA for the effects of time and treatment on indices of barrier function. RESULTS： Application of 1μmol/L lubiprostone to the rnucosal surface of ischemic-injured ileum in vitro induced significant elevations in TER compared to nontreated tissue. Lubiprostone also reduced mucosal-toserosal fluxes of ^3H-rnannitol and ^14C-inulin. Alternatively, application of a polyethylene laxative （PEG, 20 rnmol/L） to the mucosal surface of ischernic tissues significantly increased flux of ^3H-rnannitol and ^14C-inulin. CONCLUSION： This experiment demonstrates that lubiprostone stimulates recovery of barrier function in ischemic intestinal tissues whereas the PEG laxative had deleterious effects on mucosal repair. These results suggest that, unlike osmotic laxatives, lubiprostone stimulates repair of the injured intestinal barrier.

Impact of intestinal ischemia/reperfusion and lymph drainage on distant organs in rats

AIM:To investigate the impact of intestinal ischemia/reperfusion(I/R) injury and lymph drainage on distant organs in rats.METHODS:Thirty-two Sprague-Dawley male rats,weighing 280-320 g,were randomly divided into blank,sham,I/R,and ischemia/reperfusion and drainage(I/R + D) groups(n = 8).All rats were subjected to 60 min ischemia by clamping the superior mesenteric artery,followed by 120 min reperfusion.The rats in the I/R + D group received intestinal lymph drainage for 180 min.In the sham group,the abdominal cavity was opened for 180 min,but the rats received no treatment.The blank group served as a normal and untreated control.A chromogenic limulus assay kit was used for quantita-tive detection of serum endotoxin.The serum concentrations of tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-1β,soluble cell adhesion molecules(sICAM-1),and high mobility group protein box 1(HMGB1) were determined with an enzyme-linked immunosorbent assay kit.Histological evaluations of the intestine,liver,kidney,and lung were performed by hematoxylin and eosin staining and immunohistochemistry.HMGB1 protein expression was assayed by western blot analysis.RESULTS:The serum levels of endotoxin and HMGB1 in the I/R and I/R + D groups were significantly higher than those in the sham group(endotoxin,I/R and I/R + D vs sham:0.033 ± 0.004 EU/mL,0.024 ± 0.003 EU/mL vs 0.017 ± 0.009 EU/mL,respectively,P < 0.05;HMGB1,I/R and I/R + D vs sham:5.473 ± 0.963 EU/mL,4.906 ± 0.552 EU/mL vs 0.476 ± 0.406 EU/mL,respectively,P < 0.05).In addition,endotoxin and HMGB1 were significantly lower in the I/R + D group compared to the I/R group(P < 0.05).The serum inflammatory factors IL-6,IL-1β,and sICAM-1 in the I/R and I/R + D groups were significantly higher than those in the sham group(IL-6,I/R and I/R + D vs sham:41.773 ± 9.753 pg/mL,19.204 ± 4.136 pg/mL vs 11.566 ± 2.973 pg/mL,respectively,P < 0.05;IL-1β,I/R and I/R + D vs sham:144.646 ± 29.378 pg/mL,65.829 ± 10.888 pg/mL vs 38.178 ± 7.157 pg/mL,respectively,P < 0.05;sICAM-1,I/R and I/R + D vs sham:97.360 ± 12.714 ng/mL,48.401 ± 6.547 ng/mL vs 33.073 ± 5.957 ng/mL,respectively;P < 0.05).The serum TNF-α in the I/R group were significantly higher than in the sham group(45.863 ± 11.553 pg/mL vs 18.863 ± 6.679 pg/mL,respectively,P < 0.05).These factors were significantly lower in the I/R + D group compared to the I/R group(P < 0.05).The HMGB1 immunohistochemical staining results showed no staining or apparent injury in the blank group,and slight staining at the top of the microvillus was detected in the sham group.In the I/R group,both the top of villi and the basement membrane were stained for HMGB1 in most areas,and injury in the I/R + D group was less than that in the I/R group.HMGB1 expression in the liver,kidney,and lung of rats in the I/R + D group was significantly lower than the rats in the I/R group(P < 0.05).CONCLUSION:Lymph drainage could block the "gutlymph" pathway,improve intestinal barrier function,and attenuate distant organ injury incurred by intestinal I/R.

EFFECT OF ELECTROACUPUNCTURE OF ACUPOINTS OF THE HEART MERIDIAN ON ECG, SMALL INTESTINAL ELECTROGRAM AND EEG IN THE RABBIT WITH MYOCARDIAL ISCHEMIA

In the present paper, effects of electroacupuncture (EA) of 3 points of the Heart Meridian and other 3 points of the Lung Meridian on changes of electrocardiogram (ECG), small intestinal electrogram (SIG) and electroencephalogram (EEG) in intravenous drip of pituitrin induced myocardial ischemia rabbits. The three points of the Heart Meridian are "Shenmen" (HT 7), "Lingdao" (HT 4) and one point between HT 7 and HT 4, the 3 points of the Lung Meridian are "Taiyuan"(LU 9), Lieque (LU 7) and one point between LU 9 and LU 7. These points are punctured with filiform needles and stimulated electrically by setting the parameters being frequency of 2.5 Hz, dense sparse waves and duration of 10 min. Results display that the regulative effect of EA of the Heart Meridian is superior to that of EA of the Lung Meridian on the three indexes, showing a closer correlation between the whole Heart Meridian and activities of ECG, SIG and EEG.

Hydrogen gas and preservation of intestinal stem cells in mesenteric ischemia and reperfusion

BACKGROUND Patients with mesenteric ischemia frequently suffer from bowel necrosis even after revascularization.Hydrogen gas has showed promising effects for ischemiareperfusion injury by reducing reactive oxygen species in various animal and clinical studies.We examined intestinal tissue injury by ischemia and reperfusion under continuous initiation of 3%hydrogen gas.AIM To clarify the treatment effects and target cells of hydrogen gas for mesenteric ischemia.METHODS Three rat groups underwent 60-min mesenteric artery occlusion(ischemia),60-min reperfusion following 60-min occlusion(reperfusion),or ischemiareperfusion with the same duration under continuous 3%hydrogen gas inhalation(hydrogen).The distal ileum was harvested.Immunofluorescence staining with caspase-3 and leucine-rich repeat-containing G-protein-coupled 5(LGR5),a specific marker of intestinal stem cell,was conducted to evaluate the injury location and cell types protected by hydrogen.mRNA expressions of LGR5,olfactomedin 4(OLFM4),hairy and enhancer of split 1,Jagged 2,and Neurogenic locus notch homolog protein 1 were measured by quantitative polymerase chain reaction.Tissue oxidative stress was analyzed with immunostaining for 8-hydroxy-2'-deoxyguanosine(8-OHdG).Systemic oxidative stress was evaluated by plasma 8-OHdG.RESULTS Ischemia damaged the epithelial layer at the tip of the villi,whereas reperfusion induced extensive apoptosis of the cells at the crypt base,which were identified as intestinal stem cells with double immunofluorescence stain.Hydrogen mitigated such apoptosis at the crypt base,and the LGR5 expression of the tissues was higher in the hydrogen group than in the reperfusion group.OLFM4 was also relatively higher in the hydrogen group,whereas other measured RNAs were comparable between the groups.8-OHdG concentration was high in the reperfusion group,which was reduced by hydrogen,particularly at the crypt base.Serum 8-OHdG concentrations were relatively higher in both reperfusion and hydrogen groups without significance.CONCLUSION This study demonstrated that hydrogen gas inhalation preserves intestinal stem cells and mitigates oxidative stress caused by mesenteric ischemia and reperfusion.

TNF-α and plasma D(-)-lactate levels in rats after intestinal ischemia and reperfusion

Objective To study the potential role of tumor necrosis factor-α (TNF-α) induction in the development of mucosal barrier dysfunction in rats caused by acute intestinal ischemia-reperfusion injury, and to examine whether pretreatment with monoclonal antibody against TNF-α (TNF-α MoAb) would affect the release of D(-)-lactate after local gut ischemia followed by reperfusion. Methods Anesthetized Sprague-Dawley rats underwent superior mesenteric artery occlusion for 75 min followed by reperfusion for 6 hr. The rats were treated intravenously with either TNF-α MoAb (20 mg/kg) or albumin (20 mg/kg) 30 min prior to the onset of ischemia. Plasma D(-)-lactate levels were measured in both the portal and systemic blood by an enzymatic spectrophotometric assay. Intestinal TNF-αmRNA expression as well as protein levels were also measured at various intervals. In addition, a postmortem examination was performed together with a macropathological evaluation based on a four-grade scoring system.Results Intestinal ischemia resulted in a significant elevation in D(-)-lactate levels in the portal vein blood in both the control and treatment groups ( P ＜0.05). However, animals pretreated with TNF-α MoAb at 6 hr after reperfusion showed significant attenuation of an increase in both portal and systemic D(-)-lactate levels when compared with those only receiving albumin (P ＜ 0.05). In the control animals, a remarkable rise in intestinal TNF-α level was measured at 0.5 hr after clamp release ( P ＜ 0.01); however, prophylactic treatment with TNF-α MoAb completely annulled the increase of local TNF-α levels seen in the control animals. Similarly, after anti-TNF-α MoAb administration, intestinal TNF-α mRNA expression was markedly inhibited, which showed significant differences when compared with the control group at 0.5 hr, 2 hr and 6 hr after the release of occlusion ( P ＜ 0.05-0.01 ). In addition, the pathological examination showed marked intestinal lesions that formed during ischemia, which were much worse upon reperfusion,particularly at the 6 hr time point. These acute injuries were obviously attenuated in animals receiving TNF-α MoAb.Conclusions It appeared that acute intestinal ischemia was associated with failure of the mucosal barrier, resulting in increased plasma D(-)-lactate levels in both portal and systemic blood. These results suggest that TNF-α appears to be involved in the development of local damage associated with intestinal ischemic injury. Moreover, prophylactic treatment with TNF-α MoAb exerts preventive effects on ischemia/ reperfusion-induced circulating D (-)-lactate elevation and gut injury. ( J Geriatr Cardiol 2004;1(2):119-124. )

Intestinal microcirculation dysfunction in sepsis: pathophysiology, clinical monitoring, and therapeutic interventions

BACKGROUND:Intestinal microcirculation dysfunction is an important factor that causes poor prognosis in sepsis patients and is an important pathophysiological basis for the occurrence and development of sepsis.DATA RESOURCES:PubMed,Web of Science,and China National Knowledge Infrastructure(CNKI)were searched from inception to August 1,2021.The search was limited to the English language only.Two reviewers independently identified studies related to intestinal microcirculation dysfunction in sepsis.Exclusion criteria were duplicate articles according to multiple search criteria.RESULTS:Fifty articles were included,and most of them were animal studies.These studies reported pathogenesis,including endothelial dysfunction,leukocyte recruitment and adhesion,microthrombus formation,microcirculation hypoperfusion,and redistribution of intestinal wall blood flow.The monitoring methods of intestinal microcirculation were also diverse,including handheld microscopes,intravital microscopy(IVM),laser Doppler blood flow instruments,laser speckle contrast imaging,tissue refl ectance spectrophotometry,biochemical markers of intestinal ischemia,and histopathological examination.In view of the related pathogenesis of intestinal microcirculation disorder in sepsis,existing studies also have diff erent opinions on its treatment.CONCLUSIONS:Limited by monitoring,there are few clinical studies on intestinal microcirculation dysfunction in sepsis.Related research mainly focuses on basic research,but some progress has also been made.Therefore,this review may provide a reference for future research on intestinal microcirculation dysfunction in sepsis.

Nomogram for predicting transmural bowel infarction in patients with acute superior mesenteric venous thrombosis

BACKGROUND The prognosis of acute mesenteric ischemia(AMI)caused by superior mesenteric venous thrombosis(SMVT)remains undetermined and early detection of transmural bowel infarction(TBI)is crucial.The predisposition to develop TBI is of clinical concern,which can lead to fatal sepsis with hemodynamic instability and multi-organ failure.Early resection of necrotic bowel could improve the prognosis of AMI,however,accurate prediction of TBI remains a challenge for clinicians.When determining the eligibility for explorative laparotomy,the underlying risk factors for bowel infarction should be fully evaluated.AIM To develop and externally validate a nomogram for prediction of TBI in patients with acute SMVT.METHODS Consecutive data from 207 acute SMVT patients at the Wuhan Tongji Hospital and 89 patients at the Guangzhou Nanfang Hospital between July 2005 and December 2018 were included in this study.They were grouped as training and external validation cohort.The 207 cases(training cohort)from Tongji Hospital were divided into TBI and reversible intestinal ischemia groups based on the final therapeutic outcomes.Univariate and multivariate logistic regression analyses were conducted to identify independent risk factors for TBI using the training data,and a nomogram was subsequently developed.The performance of the nomogram was evaluated with respect to discrimination,calibration,and clinical usefulness in the training and external validation cohort.RESULTS Univariate and multivariate logistic regression analyses identified the following independent prognostic factors associated with TBI in the training cohort:The decreased bowel wall enhancement(OR=6.37,P<0.001),rebound tenderness(OR=7.14,P<0.001),serum lactate levels>2 mmol/L(OR=3.14,P=0.009)and previous history of deep venous thrombosis(OR=6.37,P<0.001).Incorporating these four factors,the nomogram achieved good calibration in the training set[area under the receiver operator characteristic curve(AUC)0.860;95%CI:0.771-0.925]and the external validation set(AUC 0.851;95%CI:0.796-0.897).The positive and negative predictive values(95%CIs)of the nomogram were calculated,resulting in positive predictive values of 54.55%(40.07%-68.29%)and 53.85%(43.66%-63.72%)and negative predictive values of 93.33%(82.14%-97.71%)and 92.24%(85.91%-95.86%)for the training and validation cohorts,respectively.Based on the nomogram,patients who had a Nomo-score of more than 90 were considered to have high risk for TBI.Decision curve analysis indicated that the nomogram was clinically useful.CONCLUSION The nomogram achieved an optimal prediction of TBI in patients with AMI.Using the model,the risk for an individual patient inclined to TBI can be assessed,thus providing a rational therapeutic choice.

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 12×10^9/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.

Is there a role for Tc-99m (V) DMSA scintigraphy in ischemic colitis?

AIM: To evaluate the role of pentavalent Tc-99m dimercaptosuccinic acid [Tc-99m (V) DMSA] in the diagnosis of ischemic colitis. METHODS: Fourteen patients with endoscopically and histologically confirmed ischemic colitis were included in the study. Tc-99m (V) DMSA scintigraphy was performed within 2 d after colonoscopy. Images were considered positive when an area of increased activity was observed in the region of interest and negative when no abnormal tracer uptake was detected. RESULTS: In 3 out of the 14 patients, Tc-99m (V) DMSA images showed moderate activity in the bowel. The scintigraphic results corresponded with the endoscopic findings. In the other 11 patients, no abnormal tracer uptake was detected in the abdomen. CONCLUSION: Besides the limited number of patients, Tc-99m (V) DMSA could not be considered as a useful imaging modality for the evaluation of ischemic colitis.

A computed tomography-based radiomic model for the prediction of strangulation risk in patients with acute intestinal obstruction

Background We created and validated a computed tomography(CT)-based radiomic model using both clinical factors and the radiomic signature for assessing the strangulation risk of acute intestinal obstruction.This would assist surgeons in accurately predicting intestinal ischemia and strangulation in patients with intestinal obstruction.Methods We recruited 289 patients with acute intestinal obstruction admitted in the Affiliated Hospital of Qingdao University from January 2019 to February 2022.The patients were allocated to a training(n=226)and validation cohort(n=63).Radiomic features were collected from CT images,and the radiomic signature was extracted and used to calculate a radiomic score(Rad-score).A nomogram was constructed using the clinical features and the Rad-score,and the performance of the clinical,radiomics,and nomogram models was assessed in the two cohorts.Results Six robust features were used to construct the radiomic signature.The nomogram incorporating hemoglobin levels,C-reactive protein levels,American Society of Anesthesiologists score,time of obstruction,CT image of mesenteric fluid(P<0.05),and the signature demonstrated good predictive ability for intestinal ischemia in patients with acute intestinal obstruction,with areas under the curve of 0.892(95%confidence interval,0.837–0.947)and 0.781(95%confidence interval,0.619–0.944)for the training and validation sets,respectively.The decision curve analysis showed that this model outperformed the clinical and radiomic signature models.Conclusion The radiomic nomogram may effectively predict intestinal ischemia in patients with acute intestinal disease and may assist clinical decision-making。

Influence of cromolyn sodium and compound 48/80 administered prior to and after reperfusion on the third day＇s survival rate in a rat intestinal ischemia model

Intestinal ischemia occurs in a wide variety of clinical manifestations. The gut barrier is broken down by bacterial translocation after small intestinal ischemia reperfusion injury （IIRI）, which can result in many clinical consequences, even death. The intestinal mucosal mast cells （IMMCs） serve as a unique cellular source of large amounts of vasoactive mediators, and they can influence local tissue reactions. We and others have previously shown that IIRI could activate IMMCs, make them degranulate and release a mass of inflammatory mediators, which in turn aggravate IIRI.

Protective effect of electroacupuncture preconditioning at zúsānlǐ(足三里 ST36) on mitochondria in the intestinal ischemia/reperfusion injury

Objective： The study explored the effect of applying electroacupuncture（EA） preconditioning at ST 36 on mitochondria in rats with intestinal ischemia/reperfusion injury.Methods： Forty SD rats were divided into four sets： sham operation group（sham group）; intestinal ischemia/reperfusion group（I/R group）; EA preconditioning at ST 36 followed by intestinal ischemia/reperfusion injury（ST 36 ＋ I/R group）; EA preconditioning at the lateral site away from ST360.5 cm followed by intestinal ischemia/reperfusion injury（N＋I/R group）. For the sham group, the rats were opened abdominal cavity for 3 h and 20 min and their abdominal cavities were covered with wet gauze avoiding drying and kept on the thermostat at 37 0 C. For the ischemia/reperfusion（I/R） group,rats were anaesthetised and their abdominal cavities were opened to expose jejunum segments. The segment＇s collateral blood supply was restricted by bilateral ligation of the intestine. Next, one of the branches of a mesenteric artery was occluded with a thread for 20 min and then the thread was released after such ischemia conditions, keeping reperfusion for 3 h. For the ST36 ＋ I/R group, the electroacupuncture at ST36 was first performed, then the intestinal ischemia/reperfusion model was constructed. For the N ＋ I/R group, electroacupuncture at non ST36 acupoint, which is away from ST36 about 0.5 cm, and then the intestinal ischemia/reperfusion model was performed. Measurements of the levels of inflammatory markers tumour necrosis factor a（TNFa） and interleukin-1 beta（IL-1β）, cytochrome c（CYCS）, and the mitochondrial membrane pro-apoptotic protein（BAX）, anti-apoptotic protein Bcl-2 were performed.Results： Compared to I/R group, the intensity of cytoplasmic CYCS in intestinal tissues was significantly decreased in the ST 36 ＋ I/R group（1.65 vs. 0.18, p〈0.05）. Compared to N ＋ I/R group, the intensity of cytoplasmic CYCS in intestinal tissues was also dramatically declined in the ST 36 ＋ I/R group（1.37 vs. 0.18, p〈0.05）. The level of CYCS in mitochondria in rats in the ST 36 ＋ I/R group were appreciably increased than those of rats in the I/Rgroup（1.42 vs. 0.06, p〈0.05）, and CYCS in mitochondria was also largely expressed in ST36 ＋ I/R group than N ＋ I/R group（1.42 vs. 0.08, p〈0.05）. Bcl-2 was shown to be elevated in the ST 36 ＋ I/R group than I/R group（1.01 vs. 0.10） and N ＋ I/R group（1.01 vs. 0.09, all p〈0.05）, whereas BAX expression was greatly decreased in the ST36 ＋ I/R group than I/R group（0.11 vs.0.78） and N ＋ I/R group（0.11 vs. 0.87, all p〈0.05）.Conclusion： The results suggest the EA intervention has a protective effect upon mitochondria, preventing CYCS release and the subsequent activation of downstream apoptosis pathway. It is proposed that patients due to undergo gastrointestinal surgery get benefit from EA preconditioning at ST 36.