Gut microbiota characteristics of colorectal cancer patients in Hubei, China, and differences with cohorts from other Chinese regions.

The research on the correlation or causality between gut microbiota and the occurrence, development, and treatment of colorectal cancer (CRC) is receiving increasing emphasis. At the same time, the incidence and mortality of colorectal cancer vary among individuals and regions, as does the gut microbiota. In order to gain a better understanding of the characteristics of the gut microbiota in CRC patients and the differences between different regions, we initially compared the gut microbiota of 25 CRC patients and 26 healthy controls in the central region of China (Hubei Province) using 16S rRNA high-throughput sequencing technology. The results showed that Corynebacterium, Enterococcus, Lactobacillus, and Escherichia-Shigella were significantly enriched in CRC patients. In addition, we also compared the potential differences in functional pathways between the CRC group and the healthy control group using PICRUSt's functional prediction analysis. We then analyzed and compared it with five cohort studies from various regions of China, including Central, East, and Northeast China. We found that geographical factors may affect the composition of intestinal microbiota in CRC patients. The composition of intestinal microbiota is crucial information that influences colorectal cancer screening, early detection, and the prediction of CRC treatment outcomes. This emphasizes the importance of conducting research on CRC-related gut microbiota in various regions of China.

Reoperative extended arch repair for acute type a aortic dissection after previous cardiac surgery: insights from a relatively young redo series.

OBJECTIVES: To evaluate the impact of previous cardiac surgery (PCS) on clinical outcomes after reoperative extended arch repair for acute type A aortic dissection (ATAAD). METHODS: This study included 37 ATAAD patients with PCS (PCS group) and 992 without PCS (no-PCS group). Propensity score-matching yielded a subgroup of 36 pairs (1:1). In-hospital outcomes and mid-term survival were compared between the two groups. RESULTS: The PCS group was older (56.7 ± 14.2 vs 52.2 ± 12.6 years, p = 0.036) and underwent a longer cardiopulmonary bypass (median, 212 vs 183 min, p < 0.001) compared with the no-PCS group. Operative death occurred in 88 (8.6%) patients, exhibiting no significant difference between groups (13.5% vs 8.4%, p = 0.237). Major postoperative morbidity was observed in 431 (41.9%) patients, also showing no difference between groups (45.9% vs 41.7%, p = 0.615). Moreover, the multivariable logistic regression analysis revealed that PCS was not significantly associated with operative mortality (adjusted odds ratio [OR] 2.58, 95% confidence interval [CI] 0.91-7.29, p = 0.075) or major morbidity (adjusted OR 1.92, 95% CI 0.88-4.18, p = 0.101). The 3-year cumulative survival rates were 71.1% for the PCS group and 83.9% for the no-PCS group (log-rank p = 0.071). Additionally, Cox regression indicated that PCS was not significantly associated with midterm mortality (adjusted hazard ratio 1.40, 95% CI 0.44-4.41, p = 0.566). After matching, no significant differences were found between groups in terms of operative mortality (p > 0.999), major morbidity (p > 0.999), and midterm survival (p = 0.564). CONCLUSIONS: No significant differences were found between ATAAD patients with PCS and those without PCS regarding in-hospital outcomes and midterm survival after extended arch repair.

Protective effect of α7 nicotinic acetylcholine receptor activation on experimental colitis and its mechanism.

BACKGROUND: Inflammatory bowel disease (IBD) is a common chronic remitting disease with no satisfactory treatment. The aim of this study was to investigate the protective effect of α7 nicotinic acetylcholine receptor (α7nAChR), and to determine the underlying mechanism of its activity. METHODS: The expression and distribution of α7nAChR in the intestinal tissue of patients with ulcerative colitis and Crohn's disease were analyzed. The effects of vagal excitation on murine experimental colitis were investigated. The colitis model was induced in C57BL/6 mice by the administration of 3% dextran sulfate sodium (DSS). The therapeutic group received treatment with the α7nAChR agonist PNU-282987 by intraperitoneal injection. RESULTS: Our results showed that there was significantly increased expression of α7nAChR in colitis and Crohn's disease intestinal tissue, and its expression was mainly located in macrophages and neutrophils, which were extensively infiltrated in the disease status. Treatment with an α7nAChR agonist potently ameliorated the DSS-induced illness state, including weight loss, stool consistency, bleeding, colon shortening, and colon histological injury. α7nAChR agonist exerted anti-inflammatory effects in DSS colitis mice by suppressing the secretion of multiple types of proinflammatory factors, such as IL6, TNFα, and IL1ß, and it also inhibited the colonic infiltration of inflammatory cells by blocking the DSS-induced overactivation of the NF-κB and MAPK signaling pathways. Mechanistically, activation of α7nAChR decreased the number of infiltrated M1 macrophages in the colitis intestine and inhibited the phagocytosis ability of macrophages, which were activated in response to LPS stimulation. CONCLUSION: Thus, an α7nAChR agonist ameliorated colonic pathology and inflammation in DSS-induced colitis mice by blocking the activation of inflammatory M1 macrophages.

Extracellular vesicle-mediated communication between hepatocytes and natural killer cells promotes hepatocellular tumorigenesis.

Hepatocellular carcinoma (HCC) is frequently characterized by metabolic and immune remodeling in the tumor microenvironment. We previously discovered that liver-specific deletion of fructose-1, 6-bisphosphatase 1 (FBP1), a gluconeogenic enzyme ubiquitously suppressed in HCC tissues, promotes liver tumorigenesis and induces metabolic and immune perturbations closely resembling human HCC. However, the underlying mechanisms remain incompletely understood. Here, we reported that FBP1-deficient livers exhibit diminished amounts of natural killer (NK) cells and accelerated tumorigenesis. Using the diethylnitrosamine-induced HCC mouse model, we analyzed potential changes in the immune cell populations purified from control and FBP1-depleted livers and found that NK cells were strongly suppressed. Mechanistically, FBP1 attenuation in hepatocytes derepresses an zeste homolog 2 (EZH2)-dependent transcriptional program to inhibit PKLR expression. This leads to reduced levels of PKLR cargo proteins sorted into hepatocyte-derived extracellular vesicles (EVs), dampened activity of EV-targeted NK cells, and accelerated liver tumorigenesis. Our study demonstrated that hepatic FBP1 depletion promotes HCC-associated immune remodeling, partly through the transfer of hepatocyte-secreted, PKLR-attenuated EVs to NK cells.

Enteral nutrition ameliorates the symptoms of Crohn's disease in mice via activating special pro-resolving mediators through innate lymphoid cells.

Crohn's disease activates the inflammatory reactions to induce intestinal disorders. Enteral nutrition (EN) could exert general immunomodulatory effects. Cecal ligation and perforation (CLP) surgery was utilized to establish Crohn's disease mice models. Survival analysis, hematoxylin-eosin staining, flow cytometry, ELISA, Western blot and liquid chromatography-tandem MS were applied. Baicalein was added to inhibit lipoxygenases. The survival rate was restored and inflammatory injury, exudate neutrophils in peritoneal lavage and serum levels of IL-6 and TNF-α were ameliorated by EN treatment as compared with CLP treatment. EN also increased ILC-3 content, 5/15-LOX level and RvD1-RvD5 in peritoneal lavage. Baicalein reversed all the detected effects of EN except ILC-3 content. EN could activate special pro-resolving mediators (SPMs) through ILCs to mitigate injuries of Crohn's disease.

High-Fat Diet Promotes DSS-Induced Ulcerative Colitis by Downregulated FXR Expression through the TGFB Pathway.

Ulcerative colitis is one of the IBD which cause a chronic intestinal inflammation and dysfunctional of the mucosal barrier. For now, the incident of UC was steadily increased all over the world. It has become a novel independent risk factor of several severe diseases especially colon-rectal cancer. However, the etiology of UC was still obscure. Previous studies show that high-fat diet contributed to the pathogenesis of immune system dysregulation, and farnesoid X receptor (FXR) was also implicated in the pathogenesis of various inflammatory symptoms. Yet, their inner roles in the pathogenesis of UC have not been mentioned. In this study, we aim to investigate the role of FXR in UC. High-fat diet (HFD) promotes the progression of DSS-induced UC, shows an increasing secretion of bile acid in serum, and leads to a downregulation of FXR target genes (FXRα, Shp, and lbabp). Adding FXR agonist FexD rescues the phenotype induced by high-fat diet, whereas TGFBRI inhibitor SB431542 abrogates the restoration by FexD in DSS-induced UC mice. To further verify the relationship between the FXR and TGFB signaling pathway, we made a UC-HFD model in the Caco2 cell line. Results shows the same conclusion that FXR mitigate UC inflammation through a TGFB-dependent pathway. These results expand the role of FXR in ulcerative colitis and suggest that FXR activation may be considered a therapeutic strategy for UC.

Factitious Disorder Presenting with Refractory Enterocutaneous Fistula that Underwent 7 Surgeries.

The formation of a post-appendicectomy fistula is rare but devastating. Major etiological factors include leakage from the appendiceal stump, neoplasm of the appendix and/or cecum, infection, inflammatory bowel disease, and distal obstruction. The management of enterocutaneous fistula involves enteral nutrition, drainage, antibiotic coverage, as well as surgical excision and segmental resection of the involved bowel. Here we present a case where a young female suffered from refractory enterocutaneous fistula after appendicectomy. Despite extensive treatments, her symptoms persisted and contradicted with objective test results. Therefore, a diagnosis of factitious disorder was suspected. After questioning, she finally admitted to having applied feces to her wound to fake fistula. It was estimated that the lifetime prevalence of factitious disorder in the general population was 0.1%, which warrants the awareness of clinicians.

[Relationship between functional constipation and brain-gut-microbiota axis].

Although with the higher prevalence, the overall treatment result of functional constipation is still not satisfied at home and abroad. The diagnosis and treatment of functional constipation are still to focus on colon itself. Functional constipation has complex interactions among intestinal flora, intestinal autonomic nerve and central nervous system. Patients with functional constipation have different degrees of mental and psychological dysfunction, and abnormal brain function can result in disorders of colon dynamics, secretion and immune function. At the same time, there is a significant imbalance of intestinal flora in patients with functional constipation. Intestinal flora plays an important role in the release of neurotransmitter and the activity of hypothalamic-pituitary-adrenal axis (HPA axis). Intestinal flora is an important regulator of development, maturity and activity of central nervous system. Therefore, the interaction in the brain-gut-microbiota axis may provide a broader strategy for the diagnosis and treatment of functional constipation and neuropsychiatric disorder.

[Effects of perioperative intestinal microecological treatment on postoperative complications and gastrointestinal function in patients with refractory functional constipation].

OBJECTIVE: To investigate the effects of perioperative intestinal microecological treatment on postoperative complications and gastrointestinal function in patients with refractory functional constipation by nonrandomized controlled trial. METHODS: A total of 198 patients with refractory functional constipation who underwent Jinling procedure in our department from 2014 to 2015 were prospectively enrolled, and were divided into conventional treatment group (n=100, routine intestinal preparation was used before operation; probiotics and prebiotics were applied if diarrhea or abdominal distention occurred after operation) and microecological treatment group (n=98, routine perioperative management was applied; probiotics, prebiotics and enteral nutrition were administered since 2 weeks before operation; probiotics and prebiotics were given again when exhaust and defecation recovered after operation). The general clinical data, postoperative complications, gastrointestinal quality of life index (GIQLI), Wexner constipation score, the incidence of abdominal distension and diarrhea during follow-up were collected. RESULTS: The baseline information was not significantly different between two groups (all P>0.05) as well as the morbidity of postoperative complication [27.6% (27/98) vs 37.0% (37/100), P=0.155]. Compared with conventional treatment group, microecological treatment group had obviously lower incidence of enteritis [2.0%(2/98) vs. 9.0% (9/100), P=0.034] and shorter postoperative hospital stay [(7.2±3.1) d vs. (9.8±3.6) d, P=0.040]. The incidences of diarrhea and abdominal distension in microecological treatment group were obviously lower than those in conventional treatment group [30.9% (29/94) vs. 46.9% (45/96), P=0.024; 44.7%(42/94) vs. 60.4%(58/96), P=0.030] at postoperative 1-month. Compared with conventional treatment group, microecological treatment group had obviously higher GIQLI (52.36 vs. 43.55, P=0.026) at postoperative 1-month. At postoperative 12-month, the incidences of diarrhea and abdominal distension decreased obviously in both two groups but without significant differences [diarrhea: 3.4% (3/89) vs. 3.3%(3/90), P=0.989; abdominal distention: 6.7% (6/89) vs. 5.6% (5/90), P=0.742]. GIQLI and Wexner score were improved but without significant differences as well (all P>0.05). CONCLUSION: Perioperative intestinal microecological treatment can obviously reduce the incidences of postoperative enteritis, early abdominal distension and early diarrhea, improve the postoperative early GIQLI, and shorten postoperative hospital stay.

[Recognition of the diagnosis and treatment of small intestinal obstruction].

Small intestinal obstruction is a common and frequent disease in general surgery. Delayed diagnosis and surgical timing, and inaccurate treatment strategy will lead to life-threatening complications. Therefore, how to diagnose and treat quickly and accurately is still a difficult problem in current gastrointestinal surgery. This paper summarizes and analyzes the diagnosis and treatment strategies of small intestinal obstruction based on current laboratory technology, medical imaging technology, perioperative management and improvement of surgical concepts. At the same time, early postoperative inflammatory small bowel obstruction, radioactive enteritis with intestinal obstruction, primary abdominal cocoon, primary pseudo obstruction are discussed according to the long-term experience of the author's department. The aim is to establish a reasonable and effective strategy for the diagnosis and treatment of common and special small intestinal obstruction.

[Operation key points and efficacy evaluation of Jinling procedure for mixed refractory constipation].

For chronic transit constipation (STC), surgery should be considered when all pharmacological interventions, biofeedback, and sacral nerve stimulation failed to relieve severe symptoms. Chronic functional constipation can be subdivided into three subtypes: colonic slow-transit constipation, outlet obstruction and mixed refractory constipation. The pathological changes of colonic slow transit and outlet obstruction constipation can influence each other. Mixed refractory constipation accounts for 90.2% of chronic constipation. Therefore the surgery procedure should solve two types of pathological changes at the same time. The Jinling procedure combines subtotal colectomy and side-to-side cecorectal anastomosis, aiming to solve the coexistence of obstructive defecation and slow-transit constipation in one operation. A total of 1 768 patients with mixed refractory constipation received Jinling procedure from January 2001 to June 2016. Our clinical practice indicates that the Jinling procedure is safe and effective for refractory slow-transit constipation associated with obstructive defecation, with minimal major complications, significant improvement of quality of life, and a high satisfaction rate after long-term follow up. The safety and efficacy of Jinling procedure are improved continually with the progress of minimally invasive surgery, surgical instruments, recovery after surgery and perioperative management. Through long-term clinical and basic research, our institute has formed the comprehensive treatment strategy, such as Jinling procedure, intestinal microecological treatment, medication, biological feedback and sacral nerve stimulation in the treatment of functional constipation.

[Short-term efficacy on fecal microbiota transplantation combined with soluble dietary fiber and probiotics in the treatment of slow transit constipation].

OBJECTIVE: To evaluate the efficacy and safety of fecal microbiota transplantation (FMT) combined with soluble dietary fiber and probiotics for slow transit constipation(STC). METHODS: Twenty-three patients with STC from Jinling Hospital, Medical School of Nanjing University were prospectively enrolled between April 2015 and January 2016. STC patients received FMT combined with soluble dietary fiber and probiotics. Fresh stool(100 g) was immediately mixed in a blender with 500 ml of 0.9% sterile saline for several seconds, which was then filtered through a gauze pad and a decreasing number of gauze screen (2.0 to 0.5 mm). The fecal bacteria suspension was stored frozen at -20centi-degree. The preparation time of FMT material was less than 1 hour. Total time of treatment was 9 days. An initial oral antibiotics(vancomycin 500 mg orally twice per day) was given for 3 consecutive days. Then the fecal microbiota(100 ml) was infused slowly(5 min) through nasojejunal tube for 6 consecutive days. After FMT, patients were recommended to receive soluble dietary fiber (pectin, 8 g/d) and probiotics (bifid triple viable capsules, twice per day) for 4 weeks. Rates of clinical improvement and remission, adverse events, constipation-related symptoms (PAC-SYM scores), bowel movements per week and gastrointestinal quality-of-life index (GIQLI) were recorded during the 12-week follow-up. This study was registered in the Clinical Trials.gov (NCT02016469). RESULTS: Among 23 patients, 7 were male, 16 were female, the mean age was (49.6±14.7) years, the body mass index was (21.2±2.2) kg/m2, the duration of constipation was (8.3±5.9) years, and the defecation frequency was 1.8±0.7 per week. Compared with pre-treatment, PAC-SYM scores decreased significantly from 2.3±0.5 to 1.3±0.4 at week 12 (P<0.01), defecation frequency increased from 1.8±0.7 per week to 4.8±2.0 per week at week 12 (P<0.01), and patients felt satisfied with improved GIQLI score (from 78.5±15.5 to 120.8±21.3, P<0.01). During the follow-up, the clinical improvement and remission of STC patients reached 69.6%(16/23) and 52.2%(12/23), respectively. No serious adverse events were observed. CONCLUSION: FMT combined with soluble dietary fiber and probiotics is safe and effective in treating slow transit constipation, which can improve the symptom and quality of life significantly.

[Efficacy and safety of the Jinling procedure in the treatment of adult Hirschsprung disease].

OBJECTIVE: To investigate the safety, efficacy and long-term outcomes of Jinling procedure in the treatment of adult Hirschsprung disease. METHODS: Clinical and follow-up data of 125 patients with adult Hirschsprung disease undergoing Jinling procedure at the Department of General Surgery between January 2000 and January 2013 were summarized. All the patients were diagnosed by CT, barium enema, anorectal pressure detection and pathology examination. Abdominal symptoms, gastrointestinal quality of life index(GIQLI, the lower score, the worse quality of life), Wexner constipation score (higher score indicated worse symptom), defecography (evaluation included rectocele, mucosal prolapse, intramucosal intussusception, perineal prolapse) and other operative complications were compared before and after operation. RESULTS: Among 125 patients, 69 were male and 56 were female with median age of (41.2±15.5) (18 to 75) years. The follow-up rates were 94.4%(118/125), 92.0%(115/125), 89.6%(112/125) and 88.0%(110/125) at postoperative months 1, 3, 6, and 12. Incidences of abdominal distension and abdominal pain were 100% and 82.4%(103/125) before operation, and were 7.3%(8/110) and 20.9%(23/110) at 12 months after surgery. Wexner score was significantly lower at postoperative months 1(8.7±2.9), 3 (7.2±2.8), 6(6.7±2.2) and 12(6.3±1.7) than that before operation (21.4±7.2) (P<0.01). GIQLI score was 51.6±11.9 before operation, though it decreased at 1 month (47.3±5.5)(P<0.05) after surgery, but increased significantly at postoperative months 3, 6, 12(68.9±8.0, 96.5±8.2, 103.2±8.6)(P<0.01). Abnormal rate of defecography was 70.4%(81/115), 48.2%(54/112) and 27.3%(30/110) at postoperative months 3, 6, 12, which was significantly lower than 91.2%(114/125) before operation (P<0.01). Morbidity of postoperative complication was 29.6%(37/125), including 5 cases of surgical site infection (4.0%), 2 of anastomotic bleeding (1.6%), 8 of anastomotic leakage (6.4%, one died of severe abdominal infection), 4 of urinary retention (3.2%), 3 of recurrent constipation (2.4%, without megacolon relapse), 11 of bowel obstruction (8.8%), 2 of anastomotic stricture(1.6%) and 2 of refractory staphylococcus aureus enteritis (1.6%, diagnosed by stool smear and culture, and both died finally). CONCLUSION: Jinling procedure is a safe and effective surgical procedure for adult Hirschsprung's disease.

[Therapeutic effect and long-term follow-up of the Jinling procedure for refractory constipation: a series of 1 100 cases].

OBJECTIVE: To investigate the safety, effectiveness and long-term results of Jinling procedure. METHODS: A total of 1 100 patients with refractory constipation were admitted to the Institute of General Surgery between February 2000 and December 2013 and received Jinling procedure. There were 217 male and 883 female patients with an average age of (45±15) years and an average duration of (275±159) months. The Jinling procedure modifies the classic procedure of subtotal colectomy with colorectal anastomosis by adding a new side-to-side cecorectal anastomosis. The general clinical data, postoperative complications, gastrointestinal quality of life index (GIQLI), Wexner constipation score, satisfaction rate, body composition, nutritional status, homeostasis, anal manometry and defecography during follow-up were collected. Statistical analysis was performed by t-test analysis, χ(2) test or Fisher's exact probability. RESULTS: The postoperative follow-up rate were 96.73%, 94.36%, 93.00% and 92.55% at 1, 3, 6, and 12 months. The satisfaction rate were 62.50%, 72.45%, 93.16% and 94.70% respectively during 1, 3, 6 and 12 months follow-up. The postoperative 1 month, GIQLI was lower than that of preoperative (P=0.038), but significantly better at postoperative 3 month than the preoperative (P=0.022), and gradually improve after then. Wexner score was significantly lower at postoperative 1 month than the preoperative (P=0.018), and with the gradually reduce. Compared to the preoperative baseline, all body composition and serum protein parameters decreased significantly at the one-month follow-up and then increased gradually over the remaining follow-up period. Weight and prealbumin were significantly higher than the preoperative at postoperative 12 month. Jinling procedure had no effect on electrolytes. All patients were detected in defecography before surgery, but these abnormal indicators were improved after surgery. Anal function, coordinated movement anorectal function, anorectal reflex and rectal sensation were injured at early postoperative, but as time goes on, these indicators gradually returned to preoperative levels, some indicators better than the preoperative level. Postoperative surgical site infection, anastomotic bleeding , anastomotic leakage, urinary retention, sexual dysfunction, recurrent constipation, bowel obstruction, anastomotic stricture and mortality rates were 4.36%, 5.45%, 6.00%, 6.91%, 0.64%, 0.45%, 8.82%, 4.00% and 0.27% respectively. CONCLUSIONS: Jinling procedure is a safe and effective surgical procedure for refractory constipation. It can improve defecation function and quality of life significantly, and has a high follow-up satisfaction rate.

Inorganic-Organic Thiol-ene Coated Mesh for Oil/Water Separation.

A highly efficient mesh for oil/water separation was fabricated by using a superhydrophobic and superoleophilic coating of thiol-ene hybrid, consisting of pentaerythritol tetra(3-mercaptopropionate) (PETMP), 2,4,6,8-tetramethyl-2,4,6,8-tetravinylcyclotetrasiloxane (TMTVSi), and hydrophobic fumed silica nanoparticles, via a simple two-step fabrication process. Spray deposition and UV curing photopolymerization were sequentially performed, during which solvent evaporation provides microscale roughness while nanoparticle aggregation forms nanoscale roughness. The hierarchical morphologies were stabilized after UV curing photopolymerization. High contact angle (>150°) and low roll-off angle (<5°) were achieved due to the multiscale roughness structure of the hierarchical morphologies. These coatings also have excellent chemical resistance, as well as temperature and pH stability, after curing.

[Expression of TMEM16A in the colon of intractable functional constipation patients and its clinical implications].

OBJECTIVE: To investigate the expression of TMEMl6A in the colon of intractable functional constipation patients and its clinical implications. METHODS: A total of 30 patients with intractable chronic functional constipation were selected as trial group (full thickness tissue of sigmoid colon), 30 patients with colon cancer as control group (distant tissues at least 5 cm away from cancer). Tissues from two groups were collected in our hospital from February 2012 to June 2014 and confirmed by pathological diagnosis. Immunofluorescence staining, RT-PCR and Western blot were performed to detect the mRNA and protein expression of TMEM16A and c-kit in colon. RESULTS: TMEM16A and c-kit protein expressions were observed in similar sites of colon tissues in two groups. Expressions of TMEM16A and C-kit in colon tissues detected by immunofluorescence, RT-PCR, and Western blotting were significantly lower in trial group than those in control group (TMEM16A: mean A 1.84±0.25 vs. 3.65±0.32, P<0.05, gray intensity ratio 0.66±0.07 vs. 1.04±0.17, P<0.05, relative mRNA 0.41±0.05 vs. 1.00, P<0.05; c-kit: mean A 3.38±0.24 vs. 5.06±0.31, gray intensity ratio 0.64±0.06 vs. 0.98±0.09, relative mRNA 0.18±0.08 vs. 1.00, all P<0.05). CONCLUSIONS: TMEM16A expression in colon tissues of intractable functional constipation patients is significantly lower and may adjust the movement of colonic smooth muscle by regulating the c-kit expression. TMEMl6A may be used as a new candidate target for diagnosis and treatment of intractable functional constipation.

[Establishment of rat slow transit constipation model by selective chemical ablation of the enteric plexus].

OBJECTIVE: To establish an innovative rat model of slow transit constipation by selective chemical ablation of the colon enteric plexus. METHODS: Sprague Dawley rats, 5-6 weeks old, were randomly divided into normal control group, sham operation group, treatment group I, II, III, IIII. The normal control group did not receive treatment. Rats in the sham operation group and the treatment groups received abdominal operation under anesthesia, and the gauze containing 0.9% normal saline, 0.05%, 0.1%, 0.25%, 0.5% benzalkonium chloride (BAC) was applied into colon for 30 minutes. Two weeks after operation, the number of feces, fecal dry weight in 24 h and gastrointestinal transit time were recorded, then hematoxylin-eosin (HE) staining, immunohistochemistry, ELISA were used for the evaluation of colonic pathology, enteric plexus, Interstitial cells of Cajal and neurotransmitters 5-hydroxytryptamine(5-HT). RESULTS: Compared to the normal control group and the sham operation group, the gastrointestinal transit time was significantly prolonged and fecal dry weight was lower in the treatment group II, III (all P<0.05). HE and immunohistochemical staining showed varying degrees of pathological changes in the treatment groups and in line with the pathological changes of slow transit constipation. 5-HT concentration reduced significantly in treatment group III compared to other groups (P<0.01). CONCLUSION: The animal model of STC is successfully established by applying 0.25% BAC selective chemical ablation of the colon enteric plexus. This model is simple, stable, and is more in line with pathological changes of slow transit constipation.

The influence of extracorporeal membrane oxygenation therapy on intestinal mucosal barrier in a porcine model for post-traumatic acute respiratory distress syndrome.

BACKGROUND: It is unclear at present whether extracorporeal membrane oxygenation (ECMO) therapy can improve intestinal mucous barrier function through increased perfusion. The present study establishes an animal model for post-traumatic acute respiratory distress syndrome (ARDS) and evaluates the effect of v-vECMO treatment on the intestinal mucosal barrier. METHOD: Pulmonary contusion combined with ischemia-reperfusion injury was induced in 30 piglets. The animals were randomly divided into control, model, and ECMO groups. Serum I-FABP, D-lactate, and endotoxin were measured over a 24-h period. The jejunum and colon were collected post-mortem and evaluated histopathologically. The tissue was also examined using electron microscopy, and intestinal tight junction proteins (ZO-1 and occludin) were measured after 24 h of ECMO therapy. Mortality rate and cause of death were also recorded. RESULTS: The serum markers evaluating the intestinal mucosal barrier deteriorated in the model group compared to the control group (p < 0.05). At 2 h, serum I-FABP, D-lactate, and endotoxin were significantly increased in the ECMO group compared to the model group (p < 0.05). At 12 h, I-FABP and D-lactate in the ECMO group dropped to model group levels. Serum D-lactate was slightly lower in the ECMO group (p > 0.05) and serum I-FABP was significantly lower than in the model group (p < 0.05) at 24 h. Similarly, serum endotoxin was slightly lower in the ECMO group than in the model group (p > 0.05) at 24 h. After 24 h of ECMO therapy, the occludin and ZO-1 protein concentrations in jejunum and colon mucosa increased moderately compared to that in the model group (p < 0.05). Morphologic structure of the jejunum and colon did not improved significantly after ECMO therapy. Finally, we observed that ECMO therapy moderately decreased mortality (25% vs. 50%). CONCLUSION: Intestinal mucosal barrier continued to deteriorate in the model group. Although early ECMO therapy aggravates intestinal mucosal injury, the damage gradually improves later during therapy. The results show that ECMO therapy has a protective effect on the intestinal mucosal barrier in the later treatment stage.

Berberine ameliorates intestinal mucosal barrier damage induced by peritoneal air exposure.

Berberine, an isoquinoline alkaloid derived from many medicinal plants, has been extensively used to treat various gastrointestinal diseases. In the present study, we investigated whether berberine could ameliorate intestinal mucosal barrier damage induced by peritoneal air exposure for 3 h. Peritoneal air-exposure rats received 100, 150, and 200 mg/kg berberine orally via gavage four times before and after surgery. Blood and terminal ileum samples were collected 24 h after surgery. The serum D-lactate levels were determined using an enzyme-linked immunosorbent assay (ELISA) kit. Intestinal permeability was determined by measuring the intestinal clearance of fluorescein isothiocyanate (FITC)-dextran (FD4). Intestinal inflammation was assessed by measuring myeloperoxidase activity. Intestinal histopathology was also assessed. The results revealed that berberine decreased the serum D-lactate level, intestinal FD4 clearance, and myeloperoxidase activity. Edema and inflammation were reduced by berberine in the intestinal mucosa and submucosa, and the Chiu's scores, indices of intestinal mucosal injury, also decreased in the berberine-treated group. In addition, berberine exerted these protective effects in a dose-dependent manner, with a significant difference from the control group at doses of 150 and 200 mg/kg. The results suggest that berberine could ameliorate intestinal mucosal barrier damage induced by peritoneal air exposure, which is linked to its anti-inflammatory activity. Berberine may be a promising treatment for intestinal mucosal barrier damage in open abdominal surgery.

Anti-inflammatory effect of ginsenoside Rb1 contributes to the recovery of gastrointestinal motility in the rat model of postoperative ileus.

Ginsenoside Rb1 (GRb1), one of the principle active components of Panax ginseng, has been reported to reduce inflammation in various diseases. In the present study, we investigated whether GRb1 has an anti-inflammatory effect on postoperative ileus (POI) and further contributes to the recovery of gastrointestinal motility. POI was induced in rats by intestinal manipulation. The POI rats received 5, 10 and 20 mg/kg GRb1 orally via gavage four times before and after surgery. Gastrointestinal motility was assessed by charcoal transport. Systemic inflammation was assessed by serum tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6 and IL-10 concentrations, whereas intestinal inflammation was assessed by the activity of myeloperoxidase, and concentrations and gene expression of TNF-α, IL-1ß, IL-6 and IL-10 in the ileum tissue. The results revealed that GRb1 increased rat gastrointestinal transit with POI. The increased levels of systemic and intestinal inflammatory parameters in POI rats were also reduced by GRb1. In addition, GRb1 reduced systemic and intestinal inflammation and increased the gastrointestinal transit of POI rats in a dose-dependent manner, and with significance at doses of 10 and 20 mg/kg. These results suggest that GRb1 has a potent anti-inflammatory effect on POI and further contributes to the recovery of gastrointestinal motility. GRb1 may be a promising treatment for POI prophylaxis.