Ginseng polysaccharides ameliorate ulcerative colitis via regulating gut microbiota and tryptophan metabolism.

Ulcerative colitis (UC) is regarded as a recurring inflammatory disorder of the gastrointestinal tract, for which treatment approaches remain notably limited. In this study, we demonstrated that ginseng polysaccharides (GPs) could alleviate the development of dextran sulfate sodium (DSS)-induced UC as reflected by the ameliorated pathological lesions in the colon. GPs strikingly suppressed the expression levels of multiple inflammatory cytokines, as well as significantly inhibited the infiltration of inflammatory cells. Microbiota-dependent investigations by virtue of 16S rRNA gene sequencing, antibiotic treatment and fecal microbiota transplantation illustrated that GPs treatment prominently restored intestinal microbial balance predominantly through modulating the relative abundance of Lactobacillus. Additionally, GPs remarkably influenced the levels of microbial tryptophan metabolites, diminished the intestinal permeability and strengthened intestinal barrier integrity via inhibiting the 5-HT/HTR3A signaling pathway. Taken together, the promising therapeutic potential of GPs on the development of UC predominantly hinges on the capacity to suppress the expression of inflammatory cytokines as well as to influence Lactobacillus and microbial tryptophan metabolites.

A retrospective study investigating the clinical significance of body mass index in acute pancreatitis.

Background: Acute pancreatitis is an unpredictable and potentially fatal condition for which no definitive cure is currently available. Our research focused on exploring the connection between body mass index, a frequently overlooked risk factor, and both the onset and progression of acute pancreatitis. Material/Methods: A total of 247 patients with acute pancreatitis admitted to Jiangsu Provincial Hospital of Chinese Medicine from January 2021 to February 2023 were retrospectively reviewed. After screening, 117 patients with complete height and body weight data were selected for detailed assessment. Additionally, 85 individuals who underwent physical examinations at our hospital during this period were compiled to create a control group. The study received ethical approval from the ethics committee of Jiangsu Province Hospital of Chinese Medicine (Ref: No.2022NL-114-02) and was conducted in accordance with the China Good Clinical Practice in Research guidelines. Results: A significant difference in body mass index (BMI) was observed between the healthy group and acute pancreatitis (AP) patients (p < 0.05), with a more pronounced disparity noted in cases of hyperlipidemic acute pancreatitis (p < 0.01). A potential risk for AP was identified at a BMI greater than 23.56 kg/m2 (AUC = 0.6086, p < 0.05). Being in the obese stage I (95%CI, [1.11-1.84]) or having a BMI below 25.4 kg/m2 (95%CI, [1.82-6.48]) are identified as risk factors for adverse AP progression. Moreover, BMI effectively predicts the onset of acute edematous pancreatitis and acute necrotizing pancreatitis (AUC = 0.7893, p < 0.001, cut-off value = 25.88 kg/m2). A higher BMI correlates with increased recurrence rates within a short timeframe (r = 0.7532, p < 0.01). Conclusions: Elevated BMI is a risk factor for both the occurrence and progression of AP, and underweight status may similarly contribute to poor disease outcomes. BMI is crucial for risk prediction and stratification in AP and warrants ongoing monitoring and consideration.

Duplication of the transverse colon in adults: a case report and literature review.

Background: Duplication of the transverse colon is a rare gastrointestinal malformation. Its pathogenesis is still unclear, and it is extremely rare in adults. Patients often present with symptoms of tumor compression such as abdominal mass, abdominal pain, and constipation as the first manifestation. Methods and result: A patient with a duplication of the transverse colon was admitted to the Department of General Surgery of our hospital. Laparoscopic exploration found a mass at the rear of the transverse colon near the splenic flexure, and the root was connected to the middle portion of the transverse colon. Conclusion: Surgery is a radical treatment and reduces the possibility of perforation, bleeding, obstruction, and cancer.

The SMARCA4R1157W mutation facilitates chromatin remodeling and confers PRMT1/SMARCA4 inhibitors sensitivity in colorectal cancer.

Genomic studies have demonstrated a high frequency of genetic alterations in components of the SWI/SNF complex including the core subunit SMARCA4. However, the mechanisms of tumorigenesis driven by SMARCA4 mutations, particularly in colorectal cancer (CRC), remain largely unknown. In this study, we identified a specific, hotspot mutation in SMARCA4 (c. 3721C>T) which results in a conversion from arginine to tryptophan at residue 1157 (R1157W) in human CRC tissues associated with higher-grade tumors and controls CRC progression. Mechanistically, we found that the SMARCA4R1157W mutation facilitated its recruitment to PRMT1-mediated H4R3me2a (asymmetric dimethylation of Arg 3 in histone H4) and enhanced the ATPase activity of SWI/SNF complex to remodel chromatin in CRC cells. We further showed that the SMARCA4R1157W mutant reinforced the transcriptional expression of EGFR and TNS4 to promote the proliferation of CRC cells and patient-derived tumor organoids. Importantly, we demonstrated that SMARCA4R1157W CRC cells and mutant cell-derived xenografts were more sensitive to the combined inhibition of PRMT1 and SMARCA4 which act synergistically to suppress cell proliferation. Together, our findings show that SMARCA4-R1157W is a critical activating mutation, which accelerates CRC progression through facilitating chromatin recruitment and remodeling. Our results suggest a potential precision therapeutic strategy for the treatment of CRC patients carrying the SMARCA4R1157W mutation.

Transcutaneous Electrical Acupoint Stimulation Improves Postoperative Sleep Quality in Patients Undergoing Laparoscopic Gastrointestinal Tumor Surgery: A Prospective, Randomized Controlled Trial.

INTRODUCTION: This study was conducted to observe the effect of transcutaneous electrical acupoint stimulation (TEAS) on the postoperative sleep quality of patients undergoing gastrointestinal tumor surgery and to verify the possible mechanism. METHODS: Eighty-three patients were allocated to the TEAS or Sham group. Patients in the TEAS group received TEAS treatment (disperse-dense waves; frequency, 2/100 Hz) on bilateral Shenmen (HT7), Neiguan (PC6) and Zusanli (ST36) points for 30 min each time, total three times in the perioperative period. In the Sham group, electrodes were placed; however, no current was given. Sleep quality was assessed on the day before surgery (P1) and the first and third days after surgery (D1 and D3) using the Pittsburgh Sleep Quality Index (PSQI) and Athens Insomnia Scale (AIS). Postoperative pain was assessed using visual analog scale (VAS) 72 h postoperatively. The incidences of abdominal distension, dizziness, postoperative nausea and vomiting (PONV) and pulmonary complications were recorded. Serum levels of inflammatory cytokines and the expression of key factors of oxidative stress and key molecules of the nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) signal pathway were measured. RESULTS: TEAS ameliorated sleep quality at D1 and D3 (PSQI P < 0.05, AIS P < 0.05) and decreased postoperative pain as demonstrated by lower VAS scores compared to the Sham group (P < 0.05). The incidences of abdominal distension and PONV were also lower in the TEAS group. Markers of oxidative stress were increased (P < 0.05), and the serum concentration of interleukin-6 (IL-6) was significantly lower in the TEAS group. The key mediators of the Nrf2/ARE pathway were enhanced after TEAS. CONCLUSION: Perioperative TEAS improved postoperative sleep quality, reduced postoperative pain and alleviated postoperative adverse effects in patients undergoing laparoscopic gastrointestinal tumor surgery resection. This may be associated with activating Nrf2/ARE signal pathway and decreasing its inflammatory actions. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( http://www.chictr.org.cn/index.aspx ), ChiCTR2100054971.

Monitoring diacylglycerols in biofluids by non-isotopically paired charge derivatization combined with LC-MS/MS.

Diacylglycerols (DAGs) are important lipid mediators in cellular signaling transduction and metabolism. Imbalanced production or consumption of DAGs has a negative impact on the physiological functions of the body. However, comprehensive monitoring of structurally diverse DAGs remains a daunting task due to the rapid metabolism and ion suppression characteristics in biofluids. These bottlenecks call for developing a method that enables sensitive quantification of DAGs in biological sample. In this work, a straightforward charge derivatization strategy was developed to insert a series of structure analogs charge label, i.e., N, N-dimethylglycine (DMG) and N, N-dimethylalanine (DMA), on the free hydroxyl group of the DAGs. Owing to the existence of tertiary amino groups in charge label, the mass spectrometry ionization response of the derivatized DAGs was significantly increased in comparison with traditional metal ion adducts. After charge derivatization, the specific neutral loss diagnostic ions (DMG, 103 Da and DMA, 117 Da) were captured by mass spectrometry. Then, the DMG/DMA-oriented paired multiple reaction monitoring methods based on the characteristic diagnostic ions of the derivatized DAGs have been developed as sensitive methods for the detection (detection limit = 16 aM) and quantification (quantification limit = 62.5 aM) of DAGs in serum. Moreover, the tagged 1,2-DAGs and 1,3-DAGs sn-isomers have been well separated on the reversed-phase column in combination with ultra-performance liquid chromatography. Finally, metabolic characterizations of the tagged DAGs were further explored in L-Arginine-induced acute pancreatitis mice and resveratrol treated model mice. The results indicated that 1,2-DAGs were increased in the serum of model mice relative to normal controls and resveratrol significantly altered this metabolic abnormality. The currently established DMG/DMA-oriented paired charge derivatization strategy is promising for depicting DAGs changes more accurately in metabolic studies of lipid-related diseases and accurately evaluating drug treatment strategies.

Potential efficacious materials investigation of Yi-Yi Mixture based on Metabolome-oriented network pharmacology strategy.

Yi-Yi Mixture, an efficient Chinese medicine preparation composed of four herbal medicines, has been used in clinical practice in China for the treatment of acute pancreatitis over twenty years. However, its functional materials against acute pancreatitis remains unclear, which is a huge obstacle for quality control. In this study, a metabolome-oriented network pharmacology strategy was proposed to clarify its potential substances and further screen out quality markers. Firstly, an Ultra-High performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry method was utilized to profile the chemical constituents in Yi-Yi Mixture. Secondly, metabolic exposure of chemical constituents as well as their global metabolites produced in biological systems were profiled and defined as metabolome of Yi-Yi Mixture. Then, the metabolome targets were predicted based on network analysis. As a result, a total of 66 chemical components were characterized, including 6 stilbenes, 21 anthraquinones, 7 phenols, 13 neolignans, 3 naphthalenes and 16 other types. Moreover, metabolic profiles of YYM (32 prototypes and 37 metabolites) were analyzed in rat bio-samples. Among them, resveratrol, emodin, chrysophanol, rhein and their derivatives were detected in multiple tissues/organs, revealing their potential as key pharmacodynamic substances. These were further confirmed by metabolome-oriented network analysis and molecular docking techniques. This is the first comprehensive investigation on chemical and metabolic profiles of Yi-Yi Mixture, and the results provided scientific foundation for further research on quality control and clinical-safe medication administration.

LncRNA H19 Promoted the Epithelial to Mesenchymal Transition and Metastasis in Gastric Cancer via Activating Wnt/ß-Catenin Signaling.

BACKGROUND: Due to a combination of high morbidity and lack of effective treatments, gastric cancer (GC) remains a major cause of cancer-related death all over the world. H19, as a paternally imprinted long noncoding RNA (lncRNA), has been found dysregulated in GC. AIM: The aim of this study is to elucidate the specific mechanism of H19 in GC. METHODS: Bioinformatic analysis and quantitative real-time PCR analysis were utilized to test the expression pattern of H19 in GC tissues and cell lines. Wound healing, transwell, immunofluorescence assay, and Western blot assays were conducted to test cell malignant phenotypes. Meanwhile, TOP/FOP flash assay was to analyze the relationship of H19 and Wnt/ß-catenin signaling. Also, mice xenograft models were to evaluate the influence of H19 on tumor growth. RESULTS: H19 was overexpressed in GC tissues and cell lines and related to poor prognosis for GC patients. In vitro and in vivo assays verified the promotion of H19 on GC cell epithelial to mesenchymal transition (EMT) and metastasis. Mechanistically, H19 could induce ß-catenin to transfer into nucleus and activate Wnt/ß-catenin signaling, thus promoting EMT and metastasis of GC cells. CONCLUSION: Our findings proved the mechanism of H19-mediated metastasis via activating Wnt/ß-catenin signaling, which provides a promising target for developing new therapeutic strategies in GC.

Avoidance of urinary drainage during perioperative period of open elective colonic resection within enhanced recovery after surgery programme.

BACKGROUND: Urinary catheterization (UC) is a conventional perioperative measure for major abdominal operation. Optimization of perioperative catheter management is an essential component of the enhanced recovery after surgery (ERAS) programme. We aimed to investigate the risk factors of urinary retention (UR) after open colonic resection within the ERAS protocol and to assess the feasibility of avoiding urinary drainage during the perioperative period. METHODS: A total of 110 colonic-cancer patients undergoing open elective colonic resection between July 2014 and May 2018 were enrolled in this study. All patients were treated within our ERAS protocol during the perioperative period. Data on patients' demographics, clinicopathologic characteristics, and perioperative outcomes were collected and analysed retrospectively. RESULTS: Sixty-eight patients (61.8%) underwent surgery without any perioperative UC. Thirty patients (27.3%) received indwelling UC during the surgical procedure. Twelve (10.9%) cases developed UR after surgery necessitating UC. Although patients with intraoperative UC had a lower incidence of post-operative UR [0% (0/30) vs 15% (12/80), P = 0.034], intraoperative UC was not testified as an independent protective factor in multivariate logistic analysis. The history of prostatic diseases and the body mass index were strongly associated with post-operative UR. Six patients were diagnosed with post-operative urinary-tract infection, among whom two had intraoperative UC and four were complicated with post-operative UR requiring UC. CONCLUSION: Avoidance of urinary drainage for open elective colonic resection is feasible with the implementation of the ERAS programme as the required precondition. Obesity and a history of prostatic diseases are significant predictors of post-operative UR.

A novel nomogram for predicting liver metastasis in patients with gastrointestinal stromal tumor: a SEER-based study.

BACKGROUND: Liver metastasis (LIM) of gastrointestinal stromal tumor (GIST) is associated with poor prognosis. The present study aimed at developing and validating nomogram to predict LIM in patients with GIST, thus helping clinical diagnosis and treatment. METHODS: The data of GIST patients derived from Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2016, which were then screened by univariate and multivariate logistic regression for the construction of LIM nomogram. The model discrimination of LIM nomogram was evaluated by concordance index (C-index) and calibration plots, while the predictive accuracy and clinical values were measured by decision curve analysis (DCA) and clinical impact plot. Furthermore, we validated predictive nomogram in the internal testing set. RESULTS: A total of 3797 patients were enrolled and divided randomly into training and validating groups in a 3-to-1 ratio. After logistic regression, the significant variables were sex, tumor location, tumor size, N stage and mitotic rate. The calibration curves showed the perfect agreement between nomogram predictions and actual observations, while the DCA and clinical impact plot showed the clinical utility of LIM nomogram. C-index of the nomogram was 0.812. What's more, receiver operating characteristic curves (ROC) also showed good discrimination and calibration in the training set (AUC = 0.794, 95% CI 0.778-0.808) and the testing set (AUC = 0.775, 95% CI 0.748-0.802). CONCLUSION: The nomogram for patients with GIST can effectively predict the individualized risk of liver metastasis and provide insightful information to clinicians to optimize therapeutic regimens.

Silencing protein kinase C ζ by microRNA-25-5p activates AMPK signaling and inhibits colorectal cancer cell proliferation.

Developing novel strategies against human colorectal cancer (CRC) cells is needed. Activation of AMP-activated protein kinase (AMPK) could possibly inhibit CRC cells. Protein kinase C ζ (PKCζ) is an AMPK negative regulator. Here we found that PKCζ expression was significantly elevated in human colon cancer tissues and CRC cells. PKCζ upregulation was correlated with AMPK in-activation and mTOR complex 1 (mTORC1) over-activation. Reversely, PKCζ shRNA knockdown activated AMPK signaling and inhibited HT-29 cell proliferation. Significantly, downregulation of microRNA-25-5p (miR-25-5p), a PKCζ-targeting miRNA, could be the cause of PKCζ upregulation. Exogenous expression of miR-25-5p silenced PKCζ to activate AMPK signaling, which inhibited HT-29 cell proliferation. In vivo studies showed that HT-29 xenograft growth in mice was inhibited after expressing PKCζ shRNA or miR-25-5p. Collectively, PKCζ could be a novel oncogenic protein of human CRC. PKCζ silence, by targeted-shRNA or miR-25-5p expression, activates AMPK and inhibits HT-29 cell proliferation.

Temporary rapid bowel ligation as a damage control adjunct improves survival in a hypothermic traumatic shock swine model with multiple bowel perforations.

BACKGROUND: Primary intestinal anastomosis is not the right choice for multiple bowel perforations under hemodynamically stable conditions. Our group has employed temporary rapid bowel ligation as a damage control procedure in a hypothermic traumatic shock swine model with multiple bowel perforations and hypothesized that damage control treatment would improve survival in the setting of a damage control surgery. MATERIALS AND METHODS: The abdomen was shot one time with an experimental modified gun while pigs were hemorrhaged to a mean arterial pressure of 40 mm Hg and maintained in shock for 40 min. Cold lactated Ringer solution was gradually infused to induce hypothermia. Animals were randomized to control (no resuscitation), primary anastomosis (PA), or temporary rapid bowel ligation (damage control group, DC). Animals were resuscitated for 12 h with the shed blood and lactated Ringer solution. Delayed anastomosis was performed in DC animals after resuscitation. Surviving animals were humanely killed 24 h after operation. Systemic hemodynamic parameters were recorded and blood samples were obtained for biochemical assays. The lung and ileum was harvested at the end of the experiment for pathologic evaluation and test of wet/dry weight ratio, TNF-α level, and nuclear factor-κB activations. RESULTS: All animals suffered extreme physiologic conditions: hypothermia, severe acidosis, hypotension, and depressed cardiac output. Control animals suffered 100% mortality. Compared with the PA group, DC animals required less resuscitation fluid, normalized lactate levels faster, had lower serum creatine kinase, aspartate amino transferase levels and tissue TNF-α level and nuclear factor-κB activations, suffered less severe histopathology, had greater early survival. CONCLUSIONS: Multiple bowel perforations under hemodynamically stable conditions seem better managed with DC than with PA. Temporary rapid bowel ligation as a damage control adjunct is important to rapid control of multiple bowel perforations instead of a prolonged operative time.

A modified model of the abdominal compartment syndrome.

BACKGROUND: To develop an animal model in rats and to investigate whether an intra-abdominal pressure (IAP) of 20 mm Hg will lead to a condition comparable with the abdominal compartment syndrome in humans. METHODS: Forty Sprague-Dawley rats were used. In the study group, IAP was increased to 20 mm Hg using a nitrogen gas pneumoperitoneum for 4 hours. We also observed the next reperfusion period for another 4 hours. In the controls, IAP remained unchanged. Hemodynamic readings, peak inspiratory pressure, renal function parameters, and blood gas were obtained. Additionally, histopathologic examinations were performed. RESULTS: In the presence of intra-abdominal hypertension (IAH), mean arterial pressure was reduced, whereas central venous pressure was increased significantly. Peak inspiratory pressure remained >35 mbar in the 4 hours of IAH and recovered after decompression. Arterial Po(2) decreased substantially while Pco(2) increased soon after IAH. IAH caused a metabolic acidosis, which was further complicated by the respiratory acidosis. Decompression resulted in normocapnia but the metabolic acidosis persisted. Renal blood flow and urine output decreased obviously, whereas little change was found in blood urea nitrogen and creatinine. The histopathologic study revealed parenchymal injury in lung and intestine. CONCLUSIONS: This animal model was simple and easily reproducible. An IAP of 20 mm Hg can lead to a condition comparable with the abdominal compartment syndrome in humans.

Hydroxyethyl starch 130/0.4 augments healing of colonic anastomosis in a rat model of peritonitis.

BACKGROUND: This study was designed to investigate the role of hydroxyethyl starch (HES) 130/0.4 on the wound healing process in left colonic anastomoses in the presence of intra-abdominal sepsis. METHODS: The left colonic anastomosis was performed in 40 rats that were divided into 4 groups: (1) group SHAM, laparatomy plus cecal mobilization (n = 10); (2) group SHAM + HES, HES130/.4-treated controls (n = 10); and (3) group CLP, cecal ligation and puncture (n = 10); (4) group CLP + HES, CLP plus HES130/.4 (n = 10). HES130/.4 was administrated before the construction of colonic anastomosis, 15 mL/kg/24 hours and daily for 4 postoperative days. Anastomotic bursting pressures (ABPs) were measured in vivo on day 5. Tissue samples were obtained for analyses of hydroxyproline (HP) contents, myeloperoxidase (MPO) activity, malondialdehyde (MDA), reduced glutathione (GSH) levels, and nuclear factor-kappaB (NF-kappaB) activation. The plasma levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, d-dimer, and protein C (PC) were also measured. Anastomotic granulation tissues were fixed for transmission electron microscopic (TEM) analyses. RESULTS: Intra-abdominal sepsis led to significant decreases in colonic anastomotic bursting pressures, perianastomotic tissue HP contents, GSH levels, and plasma levels of PC, along with increases in perianastomotic tissue MPO activity, MDA levels, NF-kappaB activation, and plasma levels of TNF-alpha, IL-6, and d-dimer. However, HES130/.4 treatment significantly inhibited all these responses. TEM analyses revealed that there was a trend toward a higher density of fibroblast distribution and a higher rate of fibroblast activation in the SHAM- and HES 130/0.4-treated animals, compared with the CLP group. CONCLUSIONS: This study showed that moderate doses (15 mL/kg) of HES 130/0.4 administration significantly prevented this intraperitoneal sepsis-induced impaired anastomotic healing of the left colon. This beneficial effect of HES 130/0.4 can be mainly attributed to its anti-inflammatory and antioxidant properties and beneficial effects of modulating endothelial-associated coagulopathy.

Ethyl pyruvate prevents intestinal inflammatory response and oxidative stress in a rat model of extrahepatic cholestasis.

BACKGROUND: Ringer's ethyl pyruvate solution (REPS) has been shown to ameliorate liver injury in a murine model of extrahepatic cholestasis. The goal of the present investigation was to gain additional information about whether infusing REPS instead of Ringer's lactate solution (RLS) after inducing obstructive jaundice would be beneficial to intestinal barrier function, inflammatory response, and oxidative stress. METHODS: Male Sprague Dawley rats were divided into three groups: Group Sham (n=6), sham-treated controls; Group RLS (n=9), common bile duct ligation (CBDL) plus RLS; and Group REPS (n=9), CBDL plus REPS. On 14 d after BDL, the rats were sacrificed and intestinal permeability was analyzed. Ileal IL-6 and TNF-alpha levels, malondialdehyde (MDA), glutathione (GSH), myeloperoxidase (MPO), and NF-kappaB activity were determined. Histologic examination and apoptosis of ileum were also examined. RESULTS: Relative to sham-treated controls, CBDL in RLS-treated rats were associated with increased intestinal permeability to FITC-labeled dextran (4.51+/-0.85 versus 0.44+/-0.18, P<0.01), histopathologic damage and apoptosis (68.4+/-13.4 versus 6.7+/-1.9 pre-1000 villi cells, P<0.01). IL-6 and TNF-alpha level, MDA, MPO, and NF-kappaB activity in ileal tissues were also promoted, along with decreased GSH levels. Treatment with REPS significantly decreased intestinal permeability (3.37+/-0.71, P<0.01) and apoptosis (42.8+/-14.3 pre-1000 villi cells, P<0.01). Other changes were also significantly attenuated by treatment with REPS after CBDL. CONCLUSIONS: The present study demonstrates that administration of REPS, but not RLS, maintains intestinal barrier function and reduces intestinal oxidative damage, inflammatory response, and apoptosis in cholestatic rats. This effect of ethyl pyruvate may be useful for preventing intestinal injury in patients with biliary obstruction.

Microscopic and ultrastructural changes of the intestine in abdominal compartment syndrome.

BACKGROUND: The purpose of the study was to examine the microscopic changes of intestine villus and ultrastructural changes of tight junction in the presence of intra-abdominal hypertension (IAH) of 20 mmHg. MATERIALS AND METHODS: Forty Sprague-Daley rats (250 +/- 25 g) divided into four groups (n = 10) were studied. In 30 animals, the intra-abdominal pressure was increased to 20 mmHg for 1 hr, 2 hr, and 4 hr, respectively. The others served as controls. The specimens of the intestines were submitted to histopathology using hematoxylin and eosin staining, and to ultrastructural analysis using a scanning electron microscope. RESULTS: The histopathological study revealed different degrees of changes ranging from swelling and degeneration of villous epithelial cells to extensive denudation and collapse of the villus. Ultrastructural analysis revealed dilatation of the tight junctions and paracellular spaces in the presence of IAH. The severity of the damage was related to the time of IAH. CONCLUSIONS: Increased IAH caused a significant damage to the intestinal epithelium and a marked dilatation of intestinal tight junction, leading to the increased mucosal barrier permeability. It may explain why IAH was often associated with bacterial translocation and sepsis.

The role of oxygen-free radical in the apoptosis of enterocytes and bacterial translocation in abdominal compartment syndrome.

BACKGROUND: The purpose of this study was to study the impact of intra-abdominal hypertension (IAH) on the intestine. MATERIALS AND METHODS: One hundred and twenty Sprague-Daley rats were divided into four groups. In the ACS group, the intra-abdominal pressure (IAP) was increased to 20 mmHg. In the ACS/DE group, increased IAP was followed by decompression. In the control1 and control2 groups, the IAP remained unchanged. Malondialdehyde (MDA), myeloperoxidase (MPO), glutathione (GSH) and glutathione peroxidase (GSH-Px) enzymes of the intestine were measured. Additionally, ileal tissues were obtained for histopathological examinations and apoptosis detection. Liver, spleen and mesenteric lymph nodes were obtained for microbiological analysis. RESULTS: In the presence of IAH, MDA and MPO were increased, while GSH and GSH-Px were decreased. Microbiological analysis suggested bacterial translocation across the gut. Morphological examinations indicated that the Chiu's score and apoptotic index in the ACS/DE group were the highest in the four groups. CONCLUSIONS: Oxidative stress plays an important role in the intestinal damage and bacterial translocation in abdominal compartment syndrome. Additionally, the influence of oxygen free radicals occurs mainly during the period of reperfusion rather than during the IAH period.

Establishment of an acute superior mesenteric artery injury model for damage control surgery.

BACKGROUND: Managements of superior mesenteric artery (SMA) injuries are difficult and often result in a disappointing outcome. Damage control surgery (DCS) has been approved to be an effective and reliable strategy for severe trauma victims. We aimed to build up a severe trauma-shock-hypothermia model of SMA injuries for DCS study and determine the optimal time to institute DCS. METHODS: Pigs were anesthetized and instrumented with arterial and a thermodilution cardiac output catheter. SMA flow was interrupted while animals were hemorrhaged to 45% estimated blood volume. Pigs were maintained shock and intestine ischemia for three durations: intestine ischemia for 30 min (I-30; n = 6), 60 min (I-60; n = 6), and 90 min (I-90; n = 6). Cold lactated Ringer's (10 mL/kg) was infused to induce hypothermia. SMA was then declamped and kept in reperfusion for 6 h. Hemodynamic data and serum samples were collected during shock and resuscitation. Distal ileum was collected at the end of ischemia and reperfusion. RESULTS: All animals presented with disastrous conditions at the end of ischemia: low temperature, severe acidosis, decreased blood pressure, depressed cardiac output, and oxygen delivery. I-90 animals suffered the lowest temperature, the most severe acidosis, lowest blood pressure, and depressed cardiac output and oxygen delivery. Coagulopathy developed in I-90, whereas normal prothrombin time and thrombin time were detected in I-30 and I-60. Aspartate aminotransferase, lactate dehydrogenase, creatine kinase, and alkaline phosphatase were equally within groups (P > 0.05). All (6/6) of I-30, 83.3% (5/6) of I-60, and 16.7% (1/6) of I-90 pigs survived (P < 0.01). Base excess in I-90 was much lower than that in I-30 and I-60 animals. CONCLUSIONS: We first built up an acute SMA injury animal model for DCS investigations and determined that the optimal institution time of DCS was before 60 min after SMA injury in the trauma-shock-hypothermia swine model.