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Objective To analyze the effects of miR-181a-5p overexpression on metabolites in the small intestines of mice with subcutaneous oral cancer by detecting changes in metabolites and metabolic pathways.Methods Three groups were included in study:Control group,negative control and miR-181a-5p overexpression group.To establish a subcutaneous oral cancer model in mice,variously treated cell suspensions were subcutaneously injected into the upper right of the groin in female M-NSG severely immunodeficient mice.Changes in pathology and small intestinal tissues were assessed by HE staining.Changes in mouse body weight were also assessed.Tandem orbitrap mass spectrometry and ultra-high performance liquid chromatography-tandem time-of-flight mass spectrometry,were used to examine metabolites in the small intestines.By pre-analyzing the original data and quality rating sample data,XCMS was able to assess which metabolites were different among the groups.To identify unique metabolic pathways,KEGG enrichment analysis was used.Results A total of 170 distinct metabolites were found in the small intestinal tissues of Control and NC groups.Choline metabolism,alanine,aspartate,and glutamate metabolism,GABA synaptic metabolism,glycerophospholipid metabolism,cAMP signaling route,cancer center carbon metabolism,and niacin and niacin amine metabolic pathways were important signaling pathways for metabolite enrichment.In the NC group,16 distinct metabolites with VIP values larger than 2 were found in the small intestines compared with the OE group overexpressing miR-181a-5p.Glycerin phosphorylcholine,palmitic acid,3-hydroxybutyl carnitine,and β-hydroxybutyric acid were among the metabolites that significantly varied.The primary enhanced metabolic pathway was the choline pathway.Conclusions Mouse small intestines underwent slight changes from subcutaneous oral cancer with the greatest effect on metabolites critical for energy metabolism.The choline metabolic pathway was the pathway that selected absolutely metabolites in mouse small intestines with subcutaneous grafts of oral cancer.
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Objective:To investigate the risk factors and their warning effectiveness for postoperative intestinal barrier dysfunction (IBD) in patients with severe traumatic brain injury (sTBI).Methods:A retrospective cohort study was conducted to analyze the clinical data of 101 patients with sTBI admitted to Wuxi Branch of Zhongda Hospital Affiliated to Southeast University from May 2020 to February 2023, including 63 males and 38 females, aged 21-81 years [(53.4±14.2)years]. All the patients underwent emergency surgery. The patients were divided into IBD group ( n=67) and non-IBD group ( n=34) according to whether or not they had IBD after surgery. The gender, age, basic diseases (hypertension and diabetes), types of intracranial hematoma (subdural, epidural, and intracerebral hematoma), preoperative Glasgow Coma Scale (GCS), cerebral hernia, intraoperative initial intracranial pressure (iICP), operation time, removal of bone flap, treatment time in ICU, initiation time of enteral nutrition, and use of broad-spectrum antibiotics were recorded in the two groups. Univariate and multivariate binary Logistic regression analyses were conducted to assess the correlations between above-mentioned indicators and incidence of postoperative IBD in sTBI patients and determine the independent risk factors for sTBI. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the warning effectiveness of each risk factor for IBD. Results:The results of the univariate analysis showed that preoperative GCS, cerebral hernia, intraoperative iICP, removal of bone flap, treatment time in ICU, initiation time of enteral nutrition, and use of broad-spectrum antibiotics were significantly correlated with the incidence of IBD in sTBI patients ( P<0.05 or 0.01), while there were no correlations of IBD with gender, age, basic diseases, types of intracranial hematoma and operation time ( P>0.05). The results of the multivariate binary Logistic regression analysis showed that preoperative GCS≤5 points ( OR=2.49, 95% CI 1.17, 5.32, P<0.05), intraoperative iICP>23 mmHg (1 mmHg=0.133 kPa)( OR=1.20, 95% CI 1.03, 1.39, P<0.05), and initiation time of enteral nutrition>24 hours ( OR=10.03, 95% CI 1.26, 80.21, P<0.05) were highly correlated with postoperative IBD in sTBI patients. The results of the ROC curve analysis showed that intraoperative iICP had the highest warning value (AUC=0.91, 95% CI 0.85, 0.96), followed by preoperative GCS (AUC=0.88, 95% CI 0.82, 0.95), and initiation time of enteral nutrition had the lowest warning value (AUC=0.78, 95% CI 0.69, 0.87). Conclusions:Preoperative GCS≤5 points, intraoperative iICP>23 mmHg, and initiation time of enteral nutrition>24 hours are independent risk factors for postoperative IBD in sTBI patients. The warning value of intraoperative iICP ranks the highest for postoperative IBD in sTBI patients, followed by preoperative GCS, with initiation time of enteral nutrition having the lowest warning value.
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Objective:To explore the early coagulation function changes of penetrating intestinal firearm injury of pig in high-altitude environments.Methods:Twenty healthy long white piglets were selected and divided into the plain group and the high-altitude group using the random number table method, with 10 pigs in each group. Pigs in the plain group were placed in a plain environment at an altitude of 800 meters, while pigs in the high-altitude group were placed in an experimental chamber simulating an altitude of 6 000 meters for 48 hours. Both groups received pistol gunshot to have firearm penetrating wounds to the abdominal intestinal tract and then returned to the plain observation room. At 0, 2, 4, 8, 12 and 24 hours after injury, coagulation in the peripheral blood and fibrinolytic indexes [prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fbg), D-dimer (D-D), and fibrinogen degradation product (FDP)], thromboelastogram (TEG) [reaction time (R), clotting time (K), clot formation rate (α), maximum amplitude (MA) and coagulation composite index (CI) ], platelet parameters [platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and platelet-large cell ratio (P-LCR)] in the two groups were detected separately.Results:The PT values at 0 and 2 hours after injury in the high-altitude group were significantly lower than those in the plain group, while they were significantly higher at 8, 12 and 24 hours than those in the plain group ( P<0.01); there was no significant difference at 4 hours between the two groups ( P>0.05). The APTT values at 0, 2 and 4 hours after injury in the high-altitude group were significantly lower than those in the plain group, while they were significantly higher at 8, 12 and 24 hours after injury than those in the plain group ( P<0.01). The TT values at 0, 2 and 4 hours after the injury in the high-altitude group were significantly lower than those in the plain group, while they were significantly higher at 12 and 24 hours after injury than those in the plain group ( P<0.01); there was no significant difference at 8 hours after injury between the two groups ( P>0.05). The Fbg, D-D and FDP values at 0, 2, 4, 8, 12 and 24 hours after injury were higher in the high-altitude group than those in the plain group ( P<0.01). The R values at 0, 2 and 4 hours after injury in the high-altitude group were significantly lower than those in the plain group, while they were significantly higher at 8, 12 and 24 hours after injury than those in the plain group ( P<0.01). The K values at 0, 2, 4 and 8 hours after injury in the high-altitude group were significantly lower than those in the plain group, while they were significantly higher at 12 and 24 hours after injury than those in the plain group ( P<0.05 or 0.01). The α angles at 0, 2 and 4 hours after injury in the high-altitude group were significantly higher than those in the plain group, while they were significantly lower at 8, 12 and 24 hours after injury than those in the plain group ( P<0.01). The MA values at 0, 2 and 4 hours after the injury in the high-altitude group were significantly higher than those in the plain group, while they were significantly lower at 8, 12 and 24 hours after injury than those in the plain group ( P<0.01). The CI values at 0, 2 and 4 hours after injury in the high-altitude group were significantly higher than those in the plain group, while they were significantly lower at 8, 12 and 24 hours after injury than those in the plain group ( P<0.01). The PLT values at 0, 2, 4 and 8 hours after injury in the high-altitude group were significantly higher than those in the plain group, while they were significantly lower at 12 and 24 hours after injury than those in the plain group ( P<0.05 or 0.01). The MPV values at 0, 2, 4, 8, 12 and 24 hours after injury in the high-altitude group were significantly higher than those in the plain group ( P<0.01). The PDW values at 2, 4, 8, 12 and 24 hours after injury in the high-altitude group were significantly higher than those in the plain group ( P<0.05 or 0.01), while there was no significant difference in PDW at 0 hour after injury between the two groups ( P>0.05). The P-LCR values at 0, 2, 4, 8, 12 and 24 hours after injury in the high-altitude group were all significantly higher than those in the plain group ( P<0.01). Conclusion:Compared with the plain environments, pig intestinal firearm penetrating injury in the high-altitude environments is more prone to early hypercoagulable state accompanied by mild hyperfibrinolysis, and faster to reach a hypocoagulable state accompanied by obvious hyperfibrinolysis.
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ABSTRACT BACKGROUND: Deep penetrating endometriosis (DE) can affect abdominal and pelvic organs like the bowel and bladder, requiring treatment to alleviate symptoms. AIMS: To study and investigate clinical and surgical outcomes in patients diagnosed with DE involving the intestines, aiming to analyze the effectiveness of surgical treatments. METHODS: All cases treated from January 2021 to July 2023 were included, focusing on patients aged 18 years or older with the disease affecting the intestines. Patients without intestinal involvement and those with less than six months of post-surgery follow-up were excluded. Intestinal involvement was defined as direct invasion of the intestinal wall or requiring adhesion lysis for complete resection. Primary outcomes were adhesion lysis, rectal shaving, disc excision (no-colectomy group), and segmental resection (colectomy group) along with surgical complications like anastomotic leak and fistulas, monitored for up to 30 days. RESULTS: Out of 169 patients with DE surgically treated, 76 met the inclusion criteria. No colectomy treatment was selected for 50 (65.7%) patients, while 26 (34.2%) underwent rectosigmoidectomy (RTS). Diarrhea during menstruation was the most prevalent symptom in the RTS group (19.2 vs. 6%, p<0.001). Surgical outcomes indicated longer operative times and hospital stays for the segmental resection group, respectively 186.5 vs. 104 min (p<0.001) and 4 vs. 2 days, (p<0.001). Severe complications (Clavien-Dindo ≥3) had an overall prevalence of 6 (7.9%) cases, without any difference between the groups. There was no mortality reported. Larger lesions and specific symptoms like dyschezia and rectal bleeding were associated with a higher likelihood of RTS. Bayesian regression highlighted diarrhea close to menstruation as a strong predictor of segmental resection. CONCLUSIONS: In patients with DE involving the intestines, symptoms such as dyschezia, rectal bleeding, and menstrual period-related diarrhea predict RTS. However, severe complication rates did not differ significantly between the segmental resection group and no-colectomy group.
RESUMO RACIONAL: A endometriose profunda infiltrativa (EP) pode afetar órgãos abdominais e pélvicos, tais como o intestino e a bexiga, necessitando de tratamento para aliviar os sintomas. OBJETIVOS: Estudar e investigar resultados clínicos e cirúrgicos em pacientes com diagnóstico de EP envolvendo o intestino, visando analisar a eficácia dos tratamentos cirúrgicos. MÉTODOS: Foram incluídos todos os casos atendidos de janeiro de 2021 a julho de 2023, com foco em pacientes com 18 anos ou mais com a doença acometendo o intestino. Foram excluídos pacientes sem comprometimento intestinal e aqueles com menos de seis meses de acompanhamento pós-operatório. O envolvimento intestinal foi definido como invasão direta da parede intestinal ou necessidade de lise de aderências para ressecção completa. Os desfechos primários foram lise de aderências, raspagem retal e excisão discóide (grupo não colectomia), e ressecção segmentar (grupo colectomia), juntamente com complicações cirúrgicas como fístulas, monitoradas por até 30 dias. RESULTADOS: Das 169 pacientes com EP tratadas cirurgicamente, 76 preencheram os critérios de inclusão. Não foi indicado colectomia em 50 (65,7%) pacientes, enquanto 26 (34,2%) foram submetidos à retossigmoidectomia (RTS). A diarreia durante a menstruação foi o sintoma mais prevalente no grupo RTS (19,2% vs. 6,0%, p<0,001). Os resultados cirúrgicos indicaram tempos operatórios e internações hospitalares mais longos para o grupo de ressecção segmentar, respectivamente, 186,5 vs. 104 min (p<0,001) e 4 vs. 2 dias, (p<0,001). As complicações graves (Clavien-Dindo ≥3) tiveram prevalência global de 6 (7,9%) casos, sem diferença entre os grupos. Não houve mortalidade relatada. Lesões mais graves e sintomas específicos como disquezia e sangramento retal foram associados a maior probabilidade de indicação de RTS. A regressão bayesiana destacou a diarreia próxima à menstruação como um forte preditor de ressecção segmentar. CONCLUSÕES: Em pacientes com endometriose envolvendo os intestinos, sintomas como disquezia, sangramento retal e diarreia relacionada ao período menstrual predizem a indicação de RTS. No entanto, as taxas de complicações graves não diferiram significativamente entre o grupo de ressecção segmentar e o grupo sem colectomia.
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Objective:To evaluate the effect of dexmedetomidine on the thioredoxin-interacting protein (TXNIP)/apoptosis signal-regulated kinase 1 (ASK1) signaling pathway in a mouse model of intestinal ischemia-reperfusion (I/R).Methods:Thirty-two SPF healthy adult male C57BL/6J mice, aged 8-10 weeks, weighing 18-22 g, were divided into 4 groups ( n=8 each) using a random number table method: sham operation group (Sham group), intestinal I/R group (I/R group), TXNIP inhibitor resveratrol group (Res group) and dexmedetomidine group (Dex group). The mouse model of intestinal I/R injury was developed by clamping the superior mesenteric artery for 45 min followed by 120-min reperfusion in anesthetized animals. Resveratrol 30 mg/kg was intraperitoneally injected before developing the model in Res group, and dexmedetomidine 25 μg/kg was intraperitoneally injected at 30 min before ischemia in Dex group. Blood samples were collected by cardiac puncture at the end of 120-min reperfusion, then the mice were sacrificed, and the small intestine tissues were removed for microscopic examination and for determination of the serum diamine oxidase (DAO) concentration (by enzyme-linked immunosorbent assay) and expression of TXNIP, ASK1 and cleaved-caspase-3 in small intestinal tissues (by Western blot). The apoptosis rate of intestinal epithelial cells was calculated. The intestinal damage was assessed and scored according to Chiu. Results:Compared with group Sham, the Chiu′s score, serum DAO concentrations and apoptosis rate of intestinal epithelial cells were significantly increased, and the expression of TXNIP, ASK-1 and cleaved-caspase-3 was up-regulated in group I/R ( P<0.05). Compared with group I/R, the Chiu′s score, serum DAO concentration and apoptosis rate of intestinal epithelial cells were significantly decreased, and the expression of TXNIP, ASK-1 and cleaved-caspase-3 was down-regulated in group Res ( P<0.05). Compared with I/R group, the Chiu′s score, serum DAO concentration and apoptosis rate of intestinal epithelial cells were significantly decreased, and the expression of TXNIP, ASK-1 and cleaved-caspase-3 was down-regulated in Dex group ( P<0.05). Conclusions:The mechanism by which dexmedetomidine alleviates intestinal I/R injury may be related to inhibition of the TXNIP/ASK1 signaling pathway and reduction of cell apoptosis in mice.
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Objective:To evaluate the relationship between mitochondrial calcium uniporter protein (MCU)-mediated mitochondrial dynamics and intestinal ischemia-reperfusion (I/R) injury in mice.Methods:Twenty-four wild-type adult male C57BL/6J mice, aged 6-8 weeks, weighing 18-20 g, were divided into 4 groups ( n=6 each) using a random number table method: sham operation group (S group), intestinal I/R group (IIR group), sham operation+ MCU inhibitor Ru360 group (S+ Ru360 group) and intestinal I/R + Ru360 group (IIR+ Ru360 group). The mouse model of intestinal I/R injury was prepared by clamping the root of the superior mesenteric artery for 45 min followed by 2 h of reperfusion in anesthetized animals. Small intestinal tissues were obtained at the end of reperfusion for examination of the intestinal mucosal injury which was scored according to Chiu and for determination of the content of malondialdehyde (MDA) (TBA method), activity of superoxide dismutase (SOD) (WST-8 method), content of lactic dehydrogenase (LDH) (colorimetric method), and expression of MCU, dynamin-related protein 1 (Drp1), recombinant human mitochondrial fission 1 protein (Fis1), mitofusin-1 (Mfn1) and Mfn2 (by Western blot). Results:Compared with S and S+ Ru360 groups, the Chiu′s score and contents of MDA and LDH were significantly increased, the activity of SOD was decreased, the expression of MCU, Drp1 and Fis1 was up-regulated, and the expression of Mfn1 and Mfn2 was down-regulated in IIR and IIR+ Ru360 groups ( P<0.05). Compared with IIR group, the Chiu′s score and contents of MDA and LDH were significantly decreased, the activity of SOD was increased, the expression of MCU, Drp1 and Fis1 was down-regulated, and the expression of Mfn1 and Mfn2 was up-regulated in IIR+ Ru360 group ( P<0.05). Conclusions:The mechanism underlying intestinal I/R injury may be related to MCU-induced promotion of mitochondrial fission, reduction of mitochondrial fusion and mediation of imbalance in mitochondrial dynamics in mice.
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Objective:To evaluate the role of signal transducer and activator of transcription 3 (STAT3)/nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy in salidroside-induced attenuation of intestinal ischemia-reperfusion (I/R) injury in mice and the relationship with ferroptosis.Methods:Thirty-six SPF-grade healthy male C57BL mice, aged 6-8 weeks, weighing 20-25 g, were divided into 6 groups ( n=6 each) by a random number table method: sham operation group (S group), sham operation+ salidroside group (SS group), intestinal I/R group (IR group), intestinal I/R+ salidroside group (IS group), intestinal I/R+ salidroside+ autophagy activator rapamycin group (ISR group) and intestinal I/R+ salidroside+ STAT3 activator colivelin group (ISC group). The intestinal I/R injury model was established by clamping the superior mesenteric artery for 45 min followed by 30-min reperfusion in IR, IS, ISR and ISC groups, while the superior mesenteric artery was only isolated without clipping in S and SS groups. At 1 week before developing the model, salidroside 40 mg/kg was intraperitoneally injected once a day for 7 consecutive days in SS, IS, ISC and ISR groups, rapamycin 4 mg/kg was intraperitoneally injected once a day for 7 consecutive days in group ISR, colivelin 1 mg/kg was intraperitoneally injected once a day for 7 consecutive days in group ISC, while the equal volume of normal saline was given instead in the rest two groups. The mice were sacrificed at 30 min of reperfusion, and intestinal tissues were obtained for examination of the pathological changes after HE staining (with a optical microscope) which were scored according to Chiu and for determination of contents of malondialdehyde (MDA), Fe 2+, glutathione (GSH) and reactive oxygen species (ROS), activity of superoxide dismutase (SOD) and expression of p-STAT3, STAT3, glutathione peroxidase 4 (GPX4), NCOA4 and ferritin heavy chain 1 (FTH1) in intestinal tissues (by Western blot). Results:Compared with group S, the Chiu′s score and contents of MDA, Fe 2+ and ROS were significantly increased, the content of GSH was decreased, the activity of SOD was decreased, the expression of p-STAT3 and NCOA4 was up-regulated, the expression of GPX4 and FTH1 was down-regulated, the p-STAT3/STAT3 ratio was increased ( P<0.05), pathological injury was found in intestinal tissues, and no significant change was found in the aforementioned indexes in group IR( P>0.05). Compared with group IR, the Chiu′s score and contents of MDA, Fe 2+ and ROS were significantly decreased, GSH content was increased, SOD activity was increased, the expression of p-STAT3 and NCOA4 was down-regulated, the expression of GPX4 and FTH1 was up-regulated, p-STAT3/STAT3 ratio was decreased ( P<0.05), and the pathological injury was significantly alleviated in intestinal tissues in group IS. Compared with group IS, the Chiu′s score and contents of MDA, Fe 2+ and ROS were significantly increased, GSH content was decreased, SOD activity was decreased, the expression of p-STAT3 and NCOA4 was up-regulated, the expression of GPX4 and FTH1 was down-regulated, p-STAT3/STAT3 ratio was increased ( P<0.05), and the pathological injury was aggravated in intestinal tissues in ISR and ISC groups. There was no statistically significant difference in the expression of STAT3 among the five groups ( P>0.05). Conclusions:STAT3/NCOA4-mediated ferritinophagy is involved in the process of salidroside-induced reduction of intestinal I/R injury in mice, which may be related to inhibiting ferroptosis.
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Objective:To evaluate the role of endoplasmic reticulum stress-mediated apoptosis in proanthocyanidins-induced attenuation of intestinal ischemia-reperfusion (I/R) injury in mice.Methods:Thirty SPF healthy adult male C57BL/6 mice, aged 8-10 weeks, weighing 20-25 g, were divided into 5 groups ( n=6 each) by a random number table method: sham operation group (S group), sham operation + proanthocyanidins group (S+ PC group), intestinal I/R group (I/R group), intestinal I/R + proanthocyanidins group (I/R+ PC group) and intestinal I/R + proanthocyanidins + tunicamycin group (I/R+ PC+ TM group). The superior mesenteric artery was clamped for 60 min and reperfused for 120 min to establish a mouse intestinal I/R injury model.Proanthocyanidin 100 mg/kg was given by intragastric gavage every day 1 week before ischemia in S+ PC group, I/R+ PC group and I/R+ PC+ TM group, and the equal volume of normal saline was given for 7 consecutive days in S group and I/R group, and endoplasmic reticulum stress agonist tunicamycin 1 mg/kg was intraperitoneally injected at 24 h before ischemia in I/R+ PC+ TM group.The mice were sacrificed at 120 min of reperfusion, and the small intestinal tissues were taken for microscopic examination of the histopathological changes (using light microscopy) and for determination of the level of diamine oxidase (DAO) (by enzyme-linked immunosorbent assay), cell apoptosis (by TUNEL method), glucose regulatory protein 78 (GRP78), C/EBP-homologous protein (CHOP) and cleaved caspase-3, Bax and Bcl-2 (by Western blot). Intestinal damage was assessed and scored according to Chiu, and the apoptosis index (AI) and Bcl-2/Bax ratio were calculated. Results:Compared with S group, the Chiu′s score, level of DAO and AI were significantly increased, the expression of GRP78, CHOP, cleaved caspase-3 and Bax was up-regulated, the expression of Bcl-2 was down-regulated, the ratio of Bcl-2/Bax was decreased( P<0.05), and the pathological damage occurred in the small intestinal tissue in I/R group, and no significant change was found in the aforementioned indexes in S+ PC group ( P>0.05). Compared with I/R group, the Chiu′s score, DAO level and AI were significantly decreased, the expression of GRP78, CHOP, cleaved caspase-3 and Bax was down-regulated, the expression of Bcl-2 was up-regulated, the ratio of Bcl-2/Bax was increased( P<0.05), and the pathological injury to the small intestinal tissue was significantly reduced in I/R+ PC group. Compared with I/R+ PC group, the Chiu′s score, level of DAO and AI were significantly increased, the expression of GRP78, CHOP, cleaved caspase-3 and Bax was up-regulated, the expression of Bcl-2 was down-regulated, and the ratio of Bcl-2/Bax was decreased( P<0.05), and the pathological damage to the small intestinal tissue was aggravated in I/R+ PC+ TM group. Conclusions:Proanthocyanidins can alleviate intestinal I/R injury by inhibiting endoplasmic reticulum stress-mediated cell apoptosis in mice.
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OBJECTIVE@#To compare the effects on the heart rate variability (HRV) and the expression of the atrial natriuretic peptide (ANP) in the model rats of irritable bowel syndrome with predominant diarrhea (IBS-D) rats complicated with anxiety between moxibustion of "biaoben acupoint combination" and that of "conventional acupoint combination".@*METHODS@#Of 50 healthy SPF female SD rats, aged 3 months, 8 rats were selected randomly as a blank group, and the rest rats were prepared to be the model of IBS-D complicated with anxiety. Twenty-four rats after successfully modeled were randomized into a model group, a conventional acupoint combination group (convention group) and a biaoben acupoint combination group (biaoben group), 8 rats in each one. In the convention group, moxibustion was delivered at "Tianshu" (ST 25), "Zusanli"(ST 36) and "Shangjuxu"(ST 37); and in the biaoben group, moxibustion was applied to "Neiguan" (PC 6), "Zusanli" (ST 36), and "Guanyuan" (CV 4). One session of moxibustion took 20 min, once daily, for 14 days in total. Before and after intervention, the body mass and fecal moisture content were compared in the rats of each group; using abdominal wall withdrawal reflex, the visceral hypersensitivity was evaluated; with elevated plus maze (EPM) and light-dark box (LDB), the anxiety conditions were assessed. After intervention, HRV was compared among groups, the ultrastructure of intestinal mucosa was observed under the transmission electron microscope in the rats of each group, and ANP expression in the myocardial tissue was detected using Western blot method and immunofluorescence.@*RESULTS@#Before the intervention, compared with the blank group, the body mass and visceral pain threshold of rats were reduced in the model group, the convention group and the biaoben group (P<0.05), fecal moisture content and AWR scores (at the dilatation pressure of 40, 60 and 80 mm Hg, 1 mm Hg ≈ 0.133 kPa) were elevated (P<0.05); and time in the open arm, the open arm entry number and the total movement distance (EPM), the time spent in the light compartment, the number of dark to light transitions and the total transition distance (LDB) were decreased (P<0.05). After the intervention, compared with the blank group, in the model group, the body mass, visceral pain threshold, standard diviation of NN intervals (SDNN) and root mean square of successive RR interval differences (RMSSD) were dropped (P<0.05), fecal moisture content, AWR scores (the dilation pressures of 40, 60 and 80 mm Hg), LF/HF and ANP expression were increased (P<0.05), the time in open arm, the open arm entry number and the total movement distance (EPM), the time spent in the light compartment, the number of dark to light transitions and the total transition distance (LDB) were decreased (P<0.05). When compared with the model group, in the convention group and the biaoben group, the body mass, visceral pain threshold, SDNN and RMSSD were increased (P<0.05), fecal moisture content, AWR scores (the dilation pressures of 60 and 80 mm Hg), LF/HF and ANP expression were dropped (P<0.05), the time in open arm, the open arm entry number and the total movement distance (EPM), the time spent in the light compartment, the number of dark to light transitions and the total transition distance (LDB) were increased (P<0.05). In the biaoben group, compared with the convention group, the body mass, visceral pain threshold, SDNN and RMSSD were elevated (P<0.05), fecal moisture content, AWR score (the dilation pressure of 80 mm Hg), LF/HF and ANP expression were decreased (P<0.05), the time in open arm, the open arm entry number and the total movement distance (EPM), the time spent in the light compartment, the number of dark to light transitions and the total transition distance (LDB) were increased (P<0.05). The epithelial cells of the intestinal mucosa showed a normal morphology in the blank group, the tight junction of the cells was disrupted and the junction was loose in the model group; the tight junction was imperfect in the convention group, but it was intact in the biaoben group.@*CONCLUSION@#Compared with the conventional acupoint combination, moxibustion of biaoben acupoint combination is more effective on the symptoms of IBS-D complicated with anxiety in the model rats. The effect mechanism may be related to attenuating anxiety-like negative emotions, positively regulating HRV, stabilizing IBS-D intestinal mucosal barrier and down-regulating the expression of ANP in myocardium.
Subject(s)
Rats , Female , Animals , Irritable Bowel Syndrome/therapy , Rats, Sprague-Dawley , Moxibustion/methods , Heart Rate , Atrial Natriuretic Factor , Acupuncture Points , Anxiety/therapyABSTRACT
Objective:To evaluate the effects of electroacupuncture (EA) on mitochondrial fusion and fission during intestinal injury in mice with endotoxemia and the role of heme oxygenase-1 (HO-1).Methods:Fifty SPF-grade healthy male C57BL/6 mice, aged 8 weeks, weighing 18-22 g, were divided into 5 groups ( n=10 each) using a random number table method: control group (group C), endotoxemia group (group E), endotoxemia plus EA group (group E+ EA), endotoxemia plus EA plus hemin group (group E+ EA+ H) and endotoxemia plus EA plus Znpp-Ⅸ group (group E+ EA+ Znpp-Ⅸ). Lipopolysaccharide (LPS) was intraperitoneally injected to develop the model of endotoxemia.Before LPS injection, the HO-1 inducer hemin 100 mg/kg was intraperitoneally injected in group E+ EA+ H, and the HO-1 inhibitor zinc protoporphyrin Ⅸ 10 μmol/kg was intraperitoneally injected in group E+ EA+ Znpp-Ⅸ.At 4, 3, 2 and 1 days and 30 min prior to development of the model, Zusanli and Hegu acupoints were stimulated with electric stimulator (disperse-dense wave, frequency 2 Hz/15 Hz, at a voltage of 1 mA) for 30 min, retaining the needle until the end of the experiment on the day of development of the model.Mice were sacrificed at 6 h after development of the model, and the small intestinal tissue was obtained from the terminal ileum for examination of the pathological results (with a light microscope) and ultrastructure of mitochondria (with an electron microscope) and for determination of the levels of reactive oxygen species (ROS), ATP and diamine oxidase (DAO) and expression of dynamin-related protein 1 (Drp1), mitofusin 1 (Mfn1) and HO-1 (by Western blot). Results:Compared with group C, the level of ROS was significantly increased, ATP content and DAO activity were decreased, the expression of HO-1 and Drp1 was up-regulated, the expression of Mfn1 was down-regulated ( P<0.05), and pathological damage to small intestine tissues was found in group E. Compared with group E, the level of ROS was significantly decreased, ATP content and DAO activity were increased, the expression of HO-1 and Mfn1 was up-regulated, the expression of Drp1 was down-regulated ( P<0.05), and pathological damage to small intestine tissues was significantly attenuated in group E+ EA.Compared with group E+ EA, the level of ROS was significantly decreased, ATP content and DAO activity were increased, the expression of HO-1 and Mfn1 was up-regulated, the expression of Drp1 was down-regulated ( P<0.05), and pathological damage to small intestine tissues was significantly attenuated in group E+ EA+ H, and the level of ROS was significantly increased, ATP content and DAO activity were decreased, the expression of HO-1 and Mfn1 was down-regulated, the expression of Drp1 was up-regulated ( P<0.05), and pathological damage to small intestine tissues was accenuated in group E+ EA+ Znpp-Ⅸ. Conclusions:EA can promote mitochondrial fusion, inhibit mitochondrial fission, and alleviate intestinal damage in mice with endotoxemia, and the mechanism is related to the up-regulation of HO-1 expression.
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Objective:To evaluate the role of histone deacetylase 6 (HDAC6) in reduction of intestinal ischemia-reperfusion (I/R) injury by sodium butyrate in mice.Methods:Twenty-four SPF healthy adult male C57BL/6 mice, aged 8-10 weeks, weighing 22-25 g, were divided into 4 groups ( n=6 each) by the random number table method: sham operation group (S group), intestinal I/R group (I/R group), intestinal I/R + sodium butyrate group (I/R+ SB group), and intestinal I/R + ITSA-1+ sodium butyrate group (I/R+ I+ SB group). The model of intestinal I/R injury was established by clipping superior mesenteric artery for 45 min followed by 120 min of reperfusion in anesthetized animals.In I/R+ I+ SB group, the HDACs activator ITSA-1 0.5 mg/kg was intraperitoneally injected at 6, 3 and 1 days before ischemia.Sodium butyrate 500 mg/kg was given by intragastric administration every day one week before ischemia in I/R+ SB group and I/R+ I+ SB group, and the equal volume of normal saline was given in S group and I/R group.At 120 min of reperfusion, the mice were sacrificed and their small intestine tissues were obtained.The levels of diamine oxidase (DAO) in serum and intestinal tissues were detected by enzyme-linked immunosorbent assay.The pathological changes of small intestinal tissues were observed with a light microscope, and intestinal damage was assessed and scored according to Chiu.The expression of microtubule-associated protein 1 light chain 3 Ⅱ (LC3 Ⅱ), P62 and HDAC6 was determined by Western blot.The contents of histone H3 (H3) and acetylated histone H3 (Ac-H3) in small intestinal tissues were determined by enzyme-linked immunosorbent assay. Results:Compared with S group, the Chiu′s score, levels of DAO in serum and small intestinal tissues were significantly increased, the expression of LC3 Ⅱ and HDAC6 was up-regulated, P62 expression was down-regulated, H3 content was increased, and AC-H3 content was decreased in I/R group ( P<0.05). Compared with I/R group, the Chiu′s score, levels of DAO in serum and small intestinal tissues were significantly decreased, the expression of LC3 Ⅱ and HDAC6 was down-regulated, P62 expression was up-regulated, H3 content was decreased, and AC-H3 content was increased in I/R+ SB group ( P<0.05). Compared with I/R+ SB group, the Chiu′s score and levels of DAO in serum and small intestinal tissues were significantly increased, the expression of LC3 Ⅱ and HDAC6 was up-regulated, P62 expression was down-regulated, H3 content was increased, and AC-H3 content was decreased in I/R+ I+ SB group ( P<0.05). Conclusions:Sodium butyrate can alleviate intestinal I/R injury by inhibition of HDAC6 activity in mice, and the mechanism may be related to inhibition of autophagy and promotion of H3 acetylation.
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Objective:To evaluate the effect of artesunate on intestinal ischemia/reperfusion (I/R)-induced lung injury in mice and relationship with heme oxygenase-1 (HO-1).Methods:Twenty-four healthy SPF male C57BL/6 mice, aged 8-9 weeks, weighing 18-22 g, were divided into 4 groups ( n=6 each) using a random number table method: sham operation group (group Sham), intestinal I/R group (group I/R), artesunate group (group A), and artesunate plus HO-1 inhibitor Zinc protoporphyrin Ⅸ(ZnPP) group (group AS). The model of intestinal I/R injury was established by occluding the superior mesenteric artery for 45 min followed by 2 h reperfusion in anesthetized animals.Artesunate 40 mg/kg was injected via the tail vein at 1 h before ischemia in group A. ZnPP 7.5 mg/kg was injected via the tail vein at 12 h before ischemia, and artesunate 40 mg/kg was injected via the tail vein at 1 h before ischemia in group AS.The animals were sacrificed at the end of reperfusion, and the lung tissues were obtained for microscopic examination of the pathologic changes and for determination of the wet/dry lung weight (W/D) ratio, myeloperoxidase (MPO) activity, malondialdehyde (MDA) content, expression of interleukin-6 (IL-6) mRNA (by fluorescence quantitative polymerase chain reaction) and apoptotic index (AI) (by TUNEL). The lung injury score was assessed. Results:Compared with group Sham, the lung injury score, W/D ratio, MPO activity, MDA content and AI were significantly increased, and the expression of IL-6 mRNA was up-regulated in group I/R ( P<0.05). Compared with group I/R, the lung injury score, W/D ratio, MPO activity, MDA content and AI were significantly decreased, and the expression of IL-6 mRNA was down-regulated in group A ( P<0.05). Compared with group A, the lung injury score, W/D ratio, MPO activity, MDA content and AI were significantly increased, and the expression of IL-6 mRNA was up-regulated in group AS ( P<0.05). Conclusions:Artesunate can alleviate intestinal I/R-induced lung injury, and the mechanism may be related to activation of HO-1 in mice.
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Objective:To evaluate the role of histone deacetylase (HDAC) in sodium butyrate-induced reduction of intestinal ischemia-reperfusion (I/R) injury in mice and the relationship with oxidative stress and cell apoptosis.Methods:Twenty-four SPF healthy male C57BL mice, aged 6-8 weeks, weighing 22-25 g, were divided into 4 groups ( n=6 each) according to the random number table method: sham operation group (S group), intestinal I/R group (IR group), intestinal I/R+ sodium butyrate group (IN group) and intestinal I/R+ ITSA-1+ sodium butyrate group (INI group). In IR, IN and INI groups, the superior mesenteric artery was clamped for 45 min, followed by reperfusion for 2 h to prepare the model of intestinal I/R injury, while the superior mesenteric artery was only isolated without ligation in S group.One week before preparation of the model, sodium butyrate 500 mg/kg was intragastrically administered once a day in IN group and INI group, the HDAC activator ITSA-1 0.5 mg/kg was intraperitoneally injected three times a week in INI group, and the equal volume of normal saline was given instead in the other groups.The mice were sacrificed at 2 h of reperfusion and small intestinal tissues were obtained for microscopic examination of the pathological changes which were assessed using Chiu′s score and for determination of the content of MDA (by enzyme-linked immunosorbent assay) and expression of cleaved caspase-3 (by Western blot). Results:Compared with S group, Chiu′s score was significantly increased, and the expression of cleaved caspase-3 was up-regulated in IR, IN and INI groups, the content of MDA in small intestinal tissues was significantly increased in IR and INI groups ( P<0.05). Compared with IR group, Chiu′s score was significantly decreased in IN and INI groups, and the content of MDA was significantly decreased, and the expression of cleaved caspase-3 was down-regulated in IN group ( P<0.05). Compared with IN group, Chiu′s score and content of MDA were significantly increased, and the expression of cleaved caspase-3 was up-regulated in INI group ( P<0.05). Conclusions:HDAC is involved in sodium butyrate-induced reduction of intestinal I/R injury in mice, which is related to the inhibition of oxidative stress and cell apoptosis.
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Objective:To evaluate the role of nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy in intestinal ischemia-reperfusion (I/R) injury in mice and the relationship with ferroptosis.Methods:Thirty SPF-grade healthy male C57BL/6 mice, aged 8-10 weeks, weighing 21-25 g, were divided into 5 groups ( n=6 each) using a random number table method: sham operation group (Sham group), intestinal I/R group (I/R group), intestinal I/R + NCOA4 silencing group (I/R+ NCOA4 shRNA group), intestinal I/R + autophagy inhibitor 3-methyladenine (3-MA) group (I/R+ 3-MA group), and intestinal I/R + NCOA4 silencing + autophagy activator rapamycin (RAPA) group (I/R+ NCOA4 shRNA + RAPA group). The intestinal I/R injury model was developed by clamping the superior mesenteric artery for 45 min followed by reperfusion in anesthetized animals.At 2 weeks before developing the model, AAV-NCOA4-shRNA 1×10 11 vp was injected via the tail vein in group I/R+ NCOA4 shRNA and group I/R+ NCOA4 shRNA+ RAPA, and AAV shCtrl (adenovirus control) 1 x10 11 vp was injected in Sham, I/R and I/R+ 3-MA groups.Rapamycin 4 mg/kg was intraperitoneally injected once a day starting from 7 days before developing the model in group I/R+ NCOA4 shRNA+ RAPA.In group I/R+ 3-MA, 3-MA 10 mg/kg was intraperitoneally injected at 1 h before developing the model.The animals were sacrificed at 2 h of reperfusion, and intestinal tissues were obtained for determination of contents of malondialdehyde (MDA), glutathione (GSH) and Fe 2+ (by colorimetry), contents of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) (by enzyme-linked immunosorbent assay), and expression of NCOA4, microtubule-associated protein 1 light chain 3 (LC3), long-chain fatty acyl-CoA synthase 4 (ACSL4), ferritin heavy chain 1 (FTH1) and glutathione peroxidase 4 (GPX4) (by Western blot). The LC3Ⅱ/LC3Ⅰ ratio was calculated.Intestinal damage was assessed and scored according to Chiu. Results:Compared with group Sham, the Chiu′s score and contents of MDA, Fe 2+ , TNF-α and IL-1β were significantly increased, GSH content was decreased, the expression of NCOA4 and ACSL4 was up-regulated, LC3Ⅱ/LC3Ⅰ ratio was increased, and the expression of GPX4 and FTH1 was down-regulated in group I/R ( P<0.05). Compared with group I/R, the Chiu′s score and contents of MDA, Fe 2+ , TNF-α and IL-1β were significantly decreased, and GSH content was increased in I/R+ NCOA4 shRNA and I/R+ 3-MA groups, the expression of NCOA4 and ACSL4 was significantly down-regulated, and the expression of GPX4 and FTH1 was up-regulated in group I/R+ NCOA4 shRNA ( P<0.05), and ACSL4 expression was significantly down-regulated, LC3Ⅱ/LC3Ⅰ ratio was decreased, and the expression of GPX4 and FTH1 was up-regulated in group I/R+ 3-MA ( P<0.05). Conclusions:NCOA4-mediated ferritinophagy can promote ferroptosis, which is involved in the pathophysiological mechanism of intestinal I/R injury in mice.
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Objective:To investigate the effect of sodium octanoate on renal-intestinal ischemia- reperfusion injury (IRI) after resuscitation from traumatic cardiac arrest in pigs.Methods:Twenty-two miniature piglets with a body weight of (37.6±2.5)kg were divided into three groups according to the random-number table method: normal group ( n=7), IRI group ( n=7) and IRI-treated group ( n=8). A renal-intestinal IRI model of the pig was established by allowing femoral artery to bleed through blood pump at a rate of 2 ml·kg -1·min -1 until cardiac arrest, followed by whole blood transfusion through the femoral vein at a rate of 5 ml·kg -1·min -1 after observation for 6 minutes, and 50% of total blood loss was reinfused before resuscitation. Both the IRI group and IRI-treated group were with IRI model, while normal group was just monitored without induction of IRI. Besides, IRI-treated group was injected intravenously with sodium octanoate (30 mg/kg) for 1 hour at 5 minutes after restoration of spontaneous circulation (ROSC). (1) The rate of resuscitation success, survival rate at 4, 24 hours after resuscitation, blood loss when reaching cardiac arrest criteria and resuscitation time when reaching the ROSC criteria were compared in the three groups. (2) Levels of serum creatinine (SCr), urea nitrogen (BUN), intestinal fatty acid binding protein (iFABP) and diamine oxidase (DAO) were measured before resuscitation and at 1, 2, 4, 24 hours after resuscitation. (3) The animals were sacrificed at 24 hours post-resuscitation to harvest renal and intestinal tissues rapidly. TUNEL test was applied for the cellular apoptosis index. Prussian blue was used to detect the rate of iron deposition. Western blot analysis was used to measure levels of glutathione peroxidase 4 (GPX4) and acyl-CoA synthetase long-chain family member4 (ACSL4). Results:In three groups, all pigs survived. There was no significant difference in blood loss or resuscitation time between IRI group and IRI-treated group (all P>0.05). There was no significant difference in levels of SCr, BUN, iFABP or DAO before resuscitation and at 1, 2, 4, 24 hours after resuscitation in normal group (all P>0.05). But their levels were gradually increased at 1, 2, 4, 24 hours after resuscitation from that before resuscitation in IRI group and IRI-treated group (all P<0.01). Among three groups, levels of SCr, BUN, iFABP and DAO had no significant difference before resuscitation (all P>0.05), but showed obvious increase in IRI group and the IRI-treated group at 1, 2, 4, 24 hours after resuscitation compared with normal group, especially in IRI group (all P<0.01). In normal group, IRI group and IRI-treated group after 24 hours for resuscitation, the cellular apoptosis index of renal tissues was (2.3±0.8)%, (44.0±5.4)% and (13.8±4.3)%; the cellular apoptosis index of intestinal tissues was (2.6±0.9)%, (61.3±10.4)% and (20.8±3.7)%; the rate of iron deposition of renal tissues was (0.6±0.1)%, (3.9±1.0)% and (1.7±0.3)%; the rate of iron deposition of intestinal tissues was (0.8±0.1)%, (4.9±0.9)% and (2.1±0.5)% (all P<0.01). The cellular apoptosis index and rate of iron deposition of both renal and intestinal tissues were the highest in IRI group. The renal-intestinal expression of GPX4 in IRI group and IRI-treated group was lower than that in normal group at 24 hours after resuscitation (all P<0.05), with the lowest in IRI group. The renal-intestinal expression of ACSL4 in IRI group and IRI-treated group was higher than that in normal group at 24 hours after resuscitation (all P< 0.01), with the highest in IRI group. Conclusion:Sodium octanoate can reduce renal-intestinal IRI after resuscitation from traumatic cardiac arrest in pigs, the mechanism for which is probably due to that sodium octanoate can inhibit cellular apoptosis and reduce ferroptosis by regulating the expression levels of GPX4 and ACSL4.
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Introducción: La ingesta de cuerpos extraños en el adulto de forma intencional es un evento raro que ocurre fundamentalmente en pacientes psiquiátricos o reclusos, y puede ocasionar un problema serio que llegue a comprometer la vida del paciente. Objetivo: Presentar el caso clínico de un paciente adulto, con ingestión de varios cuerpos extraños puntiformes de diferentes tamaños, y mostrar una variante para extraerlos con el menor daño posible. Caso clínico: Se expone el caso de un paciente recluso, del sexo masculino, de 25 años de edad, que ingirió varios trozos de alambre de cobre de diferentes longitudes. Por el alto riesgo de perforación, se decide realizar una laparotomía exploradora y extracción de los cuerpos extraños a través de una gastrotomía, por el orificio apendicular sin necesidad de abrir un asa intestinal. Conclusiones: Una variante para extraer los cuerpos extraños finos que logran pasar por el ángulo de Trietz, puede ser, avanzar el cuerpo extraño a través del orificio apendicular y realizar apendicectomía complementaria y lograr de esa manera su extracción sin realizar una enterotomía(AU)
Introduction: Intentional ingestion of foreign bodies in adults is a rare event that occurs mainly in psychiatric patients or inmates, and can cause a serious problem, compromising the life of the patient. Objective: To present the clinical case of an adult patient with ingestion of several pinpoint foreign bodies of different sizes, and to show a variant to extract them with the least possible damage. Clinical case: The case is a 25-year-old male incarcerate patient who ingested several pieces of copper wire of different lengths, and due to the high risk of causing perforation, it was decided to perform an exploratory laparotomy and extraction of foreign bodies through a gastrotomy, and through the appendicular orifice without the need to open an intestinal loop. Conclusions: A possible method to extract the fine foreign bodies that manage to pass through the Trietz angle is to advance the foreign body through the appendicular orifice and perform a complementary appendectomy, thus achieving its extraction without performing an enterotomy(AU)
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Humans , Male , Adult , Appendectomy , Eating , Laparotomy , Foreign BodiesABSTRACT
Objective:To investigate the effect of atorvastatin preconditioning on intestinal ischemia-reperfusion (I/R) injury in mice and the relationship with phosphatidylinositol 3-kinase (PI3K)/serine-threonine kinase (Akt) signaling pathway.Methods:Twenty-four healthy male C57BL/6 mice, aged 6-8 weeks, weighing 18-22 g, were divided into 4 groups ( n=6 each) using a random number table method: sham operation group (S group), I/R group, atorvastatin preconditioning group (A group), atorvastatin plus PI3K inhibitor LY294002 group (AL group). Atorvastatin 10 mg/kg was given by intragastric gavage for 3 consecutive days in A and AL groups, and in addition LY294002 0.3 mg/kg was intraperitoneally injected at 30 min before the last administration of atorvastatin in AL group.Intestinal I/R was produced by occlusion of superior mesenteric artery (SMA) for 45 min followed by 2 h reperfusion in anesthetized mice.The superior mesenteric artery was only isolated but not clamped in S group.The mice were sacrificed at the end of reperfusion, and small intestinal tissues were taken for determination of the pathological changes with a light microscope after HE staining and for determination of wet to dry weight ratio(W/D ratio) and expression of PI3K, phosphorylated Akt (p-Akt), autophagy-related proteins Beclin-1, microtubule-associated protein 1 light chain 3Ⅰ (LC3Ⅰ) and LC3Ⅱ.The intestinal damage was assessed and scored according to Chiu.The ratio of LC3Ⅱ expression to LC3Ⅰ expression (LC3Ⅱ/LC3Ⅰ) was calculated. Results:Compared with S group, Chiu′s scores and W/D ratio were significantly increased, the expression of PI3K and p-Akt was down-regulated, the expression of Beclin-1 was up-regulated, and LC3Ⅱ/LC3Ⅰ ratio was increased in I/R, A and AL groups ( P<0.05). Compared with I/R group, Chiu′s scores and W/D ratio were significantly decreased, the expression of PI3K and p-Akt was up-regulated, the expression of Beclin-1 was down-regulated, and LC3Ⅱ/LC3Ⅰ ratio was decreased in A group ( P<0.05). Compared with A group, Chiu′s scores and W/D ratio were significantly increased, the expression of PI3K and p-Akt was down-regulated, the expression of Beclin-1 was up-regulated, and LC3Ⅱ/LC3Ⅰ ratio was increased in AL group ( P<0.05). Conclusion:Atorvastatin preconditioning can mitigate intestinal I/R injury in mice, and the mechanism is related to activating PI3K/Akt signaling pathway and inhibiting the level of autophagy.
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AIM: To evaluate the effect of SLC7A11 in dexmedetomidine pretreatment induced reduction of ferroptosis caused by intestinal ischemia-reperfusion (II/R) injury in mice. METHODS: Twenty-four healthy meal SPF C57BL/6J mice, aged 8 weeks, weighing 22-25 g, were randomly divided into Sham operation group (S group), intestinal I/R group (II/R group), dexmedetomidine group (DEX group) and dexmedetomidine plus SLC7A11 inhibitior group (DIKE group), with 6 mice in each group. Intestinal ischemia was induced by occluding the superior mesenteric artery for 45 min followed by 30 min of reperfusion to establish the model of II/R injury. In DEX and DIKE groups, Dexmedetomidine 25 μg/kg was intraperitoneally injected at 30 min before clamping the superior mesenteric artery. The same amount of normal saline was injected in the S group and the II/R group. In DIKE group, SLC7A11 inhibitior Imidazole ketone erastin 50 mg/kg was intraperitoneally injected at 90 min before ischemia. Mice were sacrificed 30 min after reperfusion, and small intestinal tissues in length 5 cm away from the ileocecal valvum were obtained for microscopic examination of pathological changes of intestinal mucosa and for determination of contents of Fe
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Objective:To investigate the expression of intestinal alkaline phosphatase (IAP) in intestinal mucosa with bile deficiency and the effect of bile on the expression of IAP in intestinal epithelial Caco-2 cell model.Methods:Thirty healthy male SD rats were randomly divided into control group (Ctrl, n=10), external drainage group (ED, n=10) and obstructive jaundice group (OJ, n=10). Ileum specimens were collected on the 7th day after modeling. Western blot and immunohistochemical staining were used to determine the expression of IAP in rat intestinal mucosa. Different concentrations of human bile were used to treat on Caco-2 cells, and Western blot was used to detect the changes in IAP expression in Caco-2 cells. Results:Rat models were successfully established. The expression level of IAP in the intestinal mucosa of ED group [(9.19±1.67)%] was significantly lower than that of the Ctrl group [(15.09±0.61)%, P<0.05]; the expression of IAP in the intestinal mucosa of OJ group [(6.86±1.07)%] was significantly lower than that of the Ctrl group ( P<0.05). Through in vitro cell experiments, expression of IAP in Caco-2 cells was increased in a time and dose-dependent manner when treated with human bile. Conclusions:Bile deficiency in the intestine can cause inhibition of IAP in the intestinal mucosa. Bile can promote the expression of IAP in intestinal mucosal epithelial cells.
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ABSTRACT Objective: Cystectomy with urinary diversion is the gold standard for muscle invasive bladder cancer. It also may be performed as part of pelvic exenteration for non-urologic malignancy, neurogenic bladder dysfunction, and chronic conditions that result in a non-functional bladder (e.g., interstitial cystitis, radiation cystitis). Our objective is to describe the surgical technique of urinary diversion using large intestine as a conduit whilst creating an end colostomy, thereby avoiding a primary bowel anastomosis and to show its applicability with respect to urologic conditions. Materials and Methods: We retrospectively reviewed five cases from a single institution that utilized the described method of urinary diversion with large intestine. We describe operative times, hospital length of stay (LOS), and describe post-operative complications. Results: Five patients with a variety of urologic and oncologic pathology underwent the described procedures. Their operative times ranged from 5 hours to 11 hours and one patient experienced a Clavien III complication. Conclusion: We describe five patients who underwent this procedure for various medical indications, and describe their outcomes, and believe dual diversion of urinary and gastrointestinal systems with colon as a urinary conduit to be an excellent surgical option for the appropriate surgical candidate.