Inflammatory bowel diseases are characterised by inflammation that compromises the integrity of the epithelial barrier. The intestinal epithelium is not only a static barrier but has evolved complex mechanisms to cont...Inflammatory bowel diseases are characterised by inflammation that compromises the integrity of the epithelial barrier. The intestinal epithelium is not only a static barrier but has evolved complex mechanisms to control and regulate bacterial interactions with the mucosal surface. Apical tight junction proteins are critical in the maintenance of epithelial barrier function and control of paracellular permeability. The characterisation of alterations in tight junction proteins as key players in epithelial barrier function in inflammatory bowel diseases is rapidly enhancing our understanding of critical mechanisms in disease pathogenesis as well as novel therapeutic opportunities. Here we give an overview of recent literature focusing on the role of tight junction proteins, in particular claudins, in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer.展开更多
Background： Leakage of the intestinal mucosal barrier may cause translocation of bacteria, then leading to multiorgan lhilure. This study hypothesized that rhubarb monomers might protect the gut mucosal barrier in se...Background： Leakage of the intestinal mucosal barrier may cause translocation of bacteria, then leading to multiorgan lhilure. This study hypothesized that rhubarb monomers might protect the gut mucosal barrier in sepsis through junction proteins. Methods： Healthy male Sprague-Dawley rats （weighing 230-250 g） tinder anesthesia and sedation were subjected to cecal ligation and perforation （CLP）. After surgical preparation, rats were randornly assigned to eight groups （n = 6 or 8 each group）： sham group （Group A： normal saline gavage）; sepsis group （Group B： nomlal saline gavage）; Group C （intraperitoneally, dexamethasone 0.5 mg/kg） immediately after CLP surgery; and rhubarb monomer （ 100 mg/kg in normal saline）-treated groups （Group D： rhein： Group E： emodin; Group F： 3,8-dihydroxy- l-methyl-anthraquinone-2-carboxylic acid; Group G： 1-O-caffeoyl-2-（4-hydroxy-O-cinnamoyl）-D-glucose; and Group H： daucosterol linoleate）. Animals were sacrificed after 24 h. Intestinal histology, lactulose, mannito[ concentrations were measured, and zonula occludens （ZO）-I, occludin and claudin-5 transcription （polymerase chain reaction）, translation （by Western blot analysis）, and expression （by immunohistochemistry） were also measured. Results： Intestinal histology revealed injury to intestinal mucosal villi induced by sepsis in Group B, compared with Group A. Compared with Group A （0.17 ± 0.41 ）, the pathological scores in Groups B （2.83 ± 0.41, P 〈 0.001）, C （ 1.83 ± 0.41, P 〈 0.001 ）, D （2.00 ± 0.63, P 〈 0.001）, E （ 1.83 ± 0.41, P 〈 0.001 ）, F （ 1.83 ± 0.75, P 〈 0.001 ）, G （2.17 ± 0.41, P 〈 0.001 ）,and H （ 1.83 ± 0.41, P 〈 0.001 ） were significantly increased. Lactulose/mannitol （L/M） ratio in Group B （0.046 ± 0.003） was significantly higher than in Group A （0.013 ± 0.001, P 〈 0.001） while L/M ratios in Groups C （0.028 ± 0.002, P 〈 0.001 ）, D （0.029 ± 0.003, P 〈 0.001 ）, E 展开更多
Constraint-induced movement therapy after cerebral ischemia stimulates axonal growth by decreasing expression levels of Nogo-A,RhoA,and Rho-associated kinase(ROCK)in the ischemic boundary zone.However,it remains uncle...Constraint-induced movement therapy after cerebral ischemia stimulates axonal growth by decreasing expression levels of Nogo-A,RhoA,and Rho-associated kinase(ROCK)in the ischemic boundary zone.However,it remains unclear if there are any associations between the Nogo-A/RhoA/ROCK pathway and angiogenesis in adult rat brains in pathological processes such as ischemic stroke.In addition,it has not yet been reported whether constraint-induced movement therapy can promote angiogenesis in stroke in adult rats by overcoming Nogo-A/RhoA/ROCK signaling.Here,a stroke model was established by middle cerebral artery occlusion and reperfusion.Seven days after stroke,the following treatments were initiated and continued for 3 weeks:forced limb use in constraint-induced movement therapy rats(constraint-induced movement therapy group),intraperitoneal infusion of fasudil(a ROCK inhibitor)in fasudil rats(fasudil group),or lateral ventricular injection of NEP1-40(a specific antagonist of the Nogo-66 receptor)in NEP1-40 rats(NEP1-40 group).Immunohistochemistry and western blot assay results showed that,at 2 weeks after middle cerebral artery occlusion,expression levels of RhoA and ROCK were lower in the ischemic boundary zone in rats treated with NEP1-40 compared with rats treated with ischemia/reperfusion or constraint-induced movement therapy alone.However,at 4 weeks after middle cerebral artery occlusion,expression levels of RhoA and ROCK in the ischemic boundary zone were markedly decreased in the NEP1-40 and constraint-induced movement therapy groups,but there was no difference between these two groups.Compared with the ischemia/reperfusion group,modified neurological severity scores and foot fault scores were lower and time taken to locate the platform was shorter in the constraint-induced movement therapy and fasudil groups at 4 weeks after middle cerebral artery occlusion,especially in the constraint-induced movement therapy group.Immunofluorescent staining demonstrated that fasudil promoted an immune response of nerve-regene展开更多
This study examined effects of dietary protein sources and levels on intestinal health of 21 to 35 d-old weaned piglets fed antibiotics-free diets. A total of 150 weaned piglets(21 d of age) were allotted to 5 dietary...This study examined effects of dietary protein sources and levels on intestinal health of 21 to 35 d-old weaned piglets fed antibiotics-free diets. A total of 150 weaned piglets(21 d of age) were allotted to 5 dietary treatment groups. Diets were formulated, based on corn-soybean meal, with different protein sources(fish meal and soy protein concentrate) to provide different dietary CP levels. Piglets within 5 dietary treatments were fed diets as follows, respectively: 1) control diet of 17% CP(control); 2) 19% CP diets formulated with more soy protein concentrate(SPC19); 3) fish meal(FM19); 4) 23.7% CP diets formulated with more soy protein concentrate(SPC23); 5) fish meal(FM23). The results showed that piglets from control group had higher ADG and lower incidence of diarrhea compared with those of other groups(P < 0.05). The incidence of diarrhea of piglets in FM19 group was lower than those from SPC23 group and FM23 group(P < 0.05). With the higher CP levels, villous height and villous height to crypt depth ratio of piglets in the duodenum and jejunum were decreased(P < 0.05), but crypt depth was increased(P < 0.05). Comparing control group and other groups, we found the expression of inflammatory cytokines interleukin-1β(IL-1β) and interferon-γ(IFN-γ) were increased(P < 0.05) in the jejunum and colon of piglets, as did cystic fibrosis transmembrane conductance regulators(CFTR) in the distal colon. The relative transcript abundance of Zonula occludens-1(ZO-1) in the jejunum, and occludin in the jejunum and ileum of piglets fed 23.7% CP diets were reduced compared with those fed control diet(P < 0.05). In conclusion, the 17% CP diet without in-feed antibiotics helped improve growth performance and relief of diarrhea of 21 to 35 d-old weaned piglets. Dietary CP level, rather than its source(either fish meal or soy protein concentrate), has more significant impacts on the growth performance and intestinal health of 21 to 35 d-old weaned piglets when fed antibiotics-free diets.展开更多
The FLAC3D software was used to simulate and analyze numerically the displacement, stress and plastic zone distribu-tion characteristics of a large span intersection in a deep soft rock roadway after the surrounding r...The FLAC3D software was used to simulate and analyze numerically the displacement, stress and plastic zone distribu-tion characteristics of a large span intersection in a deep soft rock roadway after the surrounding rock was excavated. Our simula-tion results show that there are two kinds of dominating factors affecting roadway stability at points of intersection, one is the angle between horizontal stress and axial direction of the roadway and the other are the angles at the points of intersection. These results are based on a study we carried out as follows: first, we analyzed the failure mechanism of a large span intersection and then we built a mechanical model of a rock pillar at one of the points of intersection. At the end of this analysis, we obtained the failure characteristics of the critical parts on the large span intersection. Given these failure characteristics, we proposed a new supporting method, i.e., a Double-Bolt Control Technology (DBCT). By way of numerical simulation, DBCT can effectively control the deformation of the surrounding rock at the points of intersection in roadways.展开更多
Traumatic brain injury induces potent inflammatory responses that can exacerbate secondary blood-brain barrier（BBB） disruption, neuronal injury, and neurological dysfunction. Dexmedetomidine is a novel α2-adrenergi...Traumatic brain injury induces potent inflammatory responses that can exacerbate secondary blood-brain barrier（BBB） disruption, neuronal injury, and neurological dysfunction. Dexmedetomidine is a novel α2-adrenergic receptor agonist that exert protective effects in various central nervous system diseases. The present study was designed to investigate the neuroprotective action of dexmedetomidine in a mouse traumatic brain injury model, and to explore the possible mechanisms. Adult male C57 BL/6 J mice were subjected to controlled cortical impact. After injury, animals received 3 days of consecutive dexmedetomidine therapy（25 μg/kg per day）. The modified neurological severity score was used to assess neurological deficits. The rotarod test was used to evaluate accurate motor coordination and balance. Immunofluorescence was used to determine expression of ionized calcium binding adapter molecule-1, myeloperoxidase, and zonula occluden-1 at the injury site. An enzyme linked immunosorbent assay was used to measure the concentration of interleukin-1β（IL-1β）, tumor necrosis factor α, and IL-6. The dry-wet weight method was used to measure brain water content. The Evans blue dye extravasation assay was used to measure BBB disruption. Western blot assay was used to measure protein expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3（NLRP3）, caspase-1 p20, IL-1β, nuclear factor kappa B（NF-κB） p65, occluding, and zonula occluden-1. Flow cytometry was used to measure cellular apoptosis. Results showed that dexmedetomidine treatment attenuated early neurological dysfunction and brain edema. Further, dexmedetomidine attenuated post-traumatic inflammation, up-regulated tight junction protein expression, and reduced secondary BBB damage and apoptosis. These protective effects were accompanied by down-regulation of the NF-κB and NLRP3 inflammasome pathways. These findings suggest that dexmedetomidine exhibits neuroprotective effects against acute（3 d展开更多
Esophageal motility abnormalities are among the main factors implicated in the pathogenesis of gastroesophageal reflux disease. The recent introduction in clinical and research practice of novel esophageal testing has...Esophageal motility abnormalities are among the main factors implicated in the pathogenesis of gastroesophageal reflux disease. The recent introduction in clinical and research practice of novel esophageal testing has markedly improved our understanding of the mechanisms contributing to the development of gastroesophageal reflux disease, allowing a better management of patients with this disorder. In this context, the present article intends to provide an overview of the current literature about esophageal motility dysfunctions in patients with gastroesophageal reflux disease. Esophageal manometry, by recording intraluminal pressure, represents the gold standard to diagnose esophagealmotility abnormalities. In particular, using novel techniques, such as high resolution manometry with or without concurrent intraluminal impedance monitoring, transient lower esophageal sphincter (LES) relaxations, hypotensive LES, ineffective esophageal peristalsis and bolus transit abnormalities have been better defined and strongly implicated in gastroesophageal reflux disease development. Overall, recent findings suggest that esophageal motility abnormalities are increasingly prevalent with increasing severity of reflux disease, from nonerosive reflux disease to erosive reflux disease and Barrett's esophagus. Characterizing esophageal dysmotility among different subgroups of patients with reflux disease may represent a fundamental approach to properly diagnose these patients and, thus, to set up the best therapeutic management. Currently, surgery represents the only reliable way to restore the esophagogastric junction integrity and to reduce transient LES relaxations that are considered to be the predominant mechanism by which gastric contents can enter the esophagus. On that ground, more in depth future studies assessing the pathogenetic role of dysmotility in patients with reflux disease are warranted.展开更多
Brain microvascular endothelial cells form the interface between nervous tissue and circulating blood, and regulate central nervous system homeostasis. Brain microvascular endothelial cells differ from peripheral endo...Brain microvascular endothelial cells form the interface between nervous tissue and circulating blood, and regulate central nervous system homeostasis. Brain microvascular endothelial cells differ from peripheral endothelial cells with regards expression of specific ion transporters and receptors, and contain fewer fenestrations and pinocytotic vesicles. Brain microvascular endothelial cells also synthesize several factors that influence blood vessel function. This review describes the morphological characteristics and functions of brain microvascular endothelial cells, and summarizes current knowledge regarding changes in brain microvascular endothelial cells during stroke progression and therapies. Future studies should focus on identifying mechanisms underlying such changes and developing possible neuroprotective therapeutic interventions.展开更多
AIM:To investigate whether electroacupuncture(EA)at Zusanli(ST36)prevents intestinal barrier and remote organ dysfunction following prolonged hemorrhagic shock through a vagus anti-inflammatory mechanism.METHODS:Sprag...AIM:To investigate whether electroacupuncture(EA)at Zusanli(ST36)prevents intestinal barrier and remote organ dysfunction following prolonged hemorrhagic shock through a vagus anti-inflammatory mechanism.METHODS:Sprague-Dawley rats were subjected to about 45%of total blood volume loss followed by delayed fluid replacement(DFR)with Ringer lactate 3h after hemorrhage.In a first study,rats were randomly divided into six groups:(1)EAN:EA at non-channel acupoints followed by DFR;(2)EA:EA at ST36 after hemorrhage followed by DFR;(3)VGX/EA:vagotomy(VGX)before EA at ST36 and DFR;(4)VGX/EAN:VGX before EAN and DFR;(5)α-bungarotoxin(α-BGT)/EA:intraperitoneal injection ofα-BGT before hemorrhage,followed by EA at ST36 and DFR;and(6)α-BGT/EAN group:α-BGT injection before hemorrhage followed by EAN and DFR.Survival and mean arterial pressure(MAP)were monitored over the next 12 h.In a second study,with the same grouping and treatment,cytokine levels in plasma and intestine,organ parameters,gut injury score,gut permeability to 4 kDa FITC-dextran,and expression and distribution of tight junction protein ZO-1 were evaluated.RESULTS:MAP was significantly lowered after blood loss;EA at ST36 improved the blood pressure at corresponding time points 3 and 12 h after hemorrhage.EA at ST36 reduced tumor necrosis factor-αand interleukin(IL)-6 levels in both plasma and intestine homogenates after blood loss and DFR,while vagotomy or intraperitoneal injection ofα-BGT before EA at ST36reversed its anti-inflammatory effects,and EA at ST36did not influence IL-10 levels in plasma and intestine.EA at ST36 alleviated the injury of intestinal villus,the gut injury score being significantly lower than that of EAN group(1.85±0.33 vs 3.78±0.59,P<0.05).EA at ST36 decreased intestinal permeability to FITCdextran compared with EAN group(856.95 ng/mL±90.65 ng/mL vs 2305.62 ng/mL±278.32 ng/mL,P<0.05).EA at ST36 significantly preserved ZO-1 protein expression and localization at 12 h after hemorrhage.However,EA at non-channel acupoints had no suc展开更多
AIM: To assess the impact of Arpin protein and tight junction(TJ) proteins in the intestinal mucosa onbacterial translocation in patients with severe acute pancreatitis(SAP).METHODS: Fifty SAP patients were identified...AIM: To assess the impact of Arpin protein and tight junction(TJ) proteins in the intestinal mucosa onbacterial translocation in patients with severe acute pancreatitis(SAP).METHODS: Fifty SAP patients were identified as study objects and then classified into two groups according to the presence of bacterial translocation(BT) in the blood [i.e., BT(+) and BT(-)].Twenty healthy individuals were included in the control group.BT was analyzed by polymerase chain reaction, colonic mucosal tissue was obtained by endoscopy and the expression of TJ proteins and Arpin protein was determined using immunofluorescence and western blotting.RESULTS: Bacterial DNA was detected in the peripheral blood of 62.0% of patients(31/50) with SAP.The expression of TJ proteins in SAP patients was lower than that in healthy controls.In contrast, Arpin protein expression in SAP patients was higher than in healthy controls(0.38 ± 0.19 vs 0.28 ± 0.16, P < 0.05).Among SAP patients, those positive for BT showed a higher level of claudin-2 expression(0.64 ± 0.27 vs 0.32 ± 0.21, P < 0.05) and a lower level of occludin(OC)(0.61 ± 0.28 vs 0.73 ± 0.32, P < 0.05) and zonula occludens-1(0.42 ± 0.26 vs 0.58 ± 0.17, P = 0.038) expression in comparison with BT(-) patients.Moreover, the level of Arpin expression in BT(+) patients was higher than in BT(-) patients(0.61 ± 0.28 vs 0.31 ± 0.24, P < 0.05).CONCLUSION: Arpin protein affects the expression of tight junction proteins and may have an impact on BT.These results contribute to a better understanding of the factors involved in bacterial translocation during acute pancreatitis.展开更多
AIM To determine the optimal treatment strategy for Siewert type Ⅱ and?Ⅲ?adenocarcinoma of the esophagogastric junction.METHODS We retrospectively reviewed the medical records of 83 patients with Siewert type?Ⅱ?and...AIM To determine the optimal treatment strategy for Siewert type Ⅱ and?Ⅲ?adenocarcinoma of the esophagogastric junction.METHODS We retrospectively reviewed the medical records of 83 patients with Siewert type?Ⅱ?and?Ⅲ?adenocarcinoma of the esophagogastric junction and calculated both an index of estimated benefit from lymph node dissection for each lymph node(LN) station and a lymph node ratio(LNR: ratio of number of positive lymph nodes to the total number of dissected lymph nodes). We used Cox proportional hazard models to clarify independent poor prognostic factors. The median duration of observation was 73 mo.RESULTS Indices of estimated benefit from LN dissection were as follows, in descending order: lymph nodes(LN) along the lesser curvature, 26.5; right paracardial LN, 22.8; left paracardial LN, 11.6; LN along the left gastric artery, 10.6. The 5-year overall survival(OS) rate was 58%. Cox regression analysis revealed that vigorous venous invasion(v2, v3)(HR = 5.99; 95%CI: 1.71-24.90) and LNR of > 0.16(HR = 4.29, 95%CI: 1.79-10.89) were independent poor prognostic factors for OS.CONCLUSION LN along the lesser curvature, right and left paracardial LN, and LN along the left gastric artery should be dissected in patients with Siewert type?Ⅱ?or?Ⅲ?adenoca rcinoma of the esophagogastric junction. Patients with vigorous venous invasion and LNR of > 0.16 should be treated with aggressive adjuvant chemotherapy to improve survival outcomes.展开更多
The oil / water two-phase flow inside T-junctions was numerically simulated with a 3-D two-fluid model, and the turbulence was described using the mixture k- ε model. Some experiments of oil / water flow inside a sin...The oil / water two-phase flow inside T-junctions was numerically simulated with a 3-D two-fluid model, and the turbulence was described using the mixture k- ε model. Some experiments of oil / water flow inside a single T-junction were conducted in the laboratory. The results show that the separating performance of T-junction largely depends on the inlet volumetric fraction and flow patterns. A reasonable agreement is reached between the numerical simulation and the experiments for both the oil fraction distribution and the separation efficiency.展开更多
Based on Siewert classification, adenocarcinomas of the esophagogastric junction （AEGs） have different behaviors of perigastric-mediastinal nodal metastasis. Siewert type I AEGs have higher incidence of mediastinal ...Based on Siewert classification, adenocarcinomas of the esophagogastric junction （AEGs） have different behaviors of perigastric-mediastinal nodal metastasis. Siewert type I AEGs have higher incidence of mediastinal nodal metastasis than those of type H or III, especially at middle-upper mediastinum. With regard to the necessity of mediastinal lymphadenectomy, theoretically, transthoracic esophagogastrectomy with complete mediastinal lymphadenectomy is suggested for Siewert type I AEGs, while transhiatal total gastrectomy with lower mediastinal and D2 perigastric lymphadenectomy is a standard surgery for type II-III AEGs. Nevertheless, the mediastinal nodal metastasis is an independent factor of poor prognosis for any type of AEG.展开更多
Severe burn injury is often accompanied by intestinal barrier dysfunction,which is closely associated with post-burn shock,bacterial translocation,systemic inflammatory response syndrome,hypercatabolism,sepsis,multipl...Severe burn injury is often accompanied by intestinal barrier dysfunction,which is closely associated with post-burn shock,bacterial translocation,systemic inflammatory response syndrome,hypercatabolism,sepsis,multiple organ dysfunction syndrome,and other complications.The intestinal epithelium forms a physical barrier that separates the intestinal lumen from the internal milieu,in which the tight junction plays a principal role.It has been well documented that after severe burn injury,many factors such as stress,ischemia/hypoxia,proinflammatory cytokines,and endotoxins can induce intestinal barrier dysfunction via multiple signaling pathways.Recent advances have provided new insights into the mechanisms and the therapeutic strategies of intestinal epithelial barrier dysfunction associated with severe burn injury.In this review,we will describe the current knowledge of the mechanisms involved in intestinal barrier dysfunction in response to severe burn injury and the emerging therapies for treating intestinal barrier dysfunction following severe burn injury.展开更多
AIM:To determine the merits of magnetic resonance cholangiopancreatography(MRCP) as the primary diagnostic test for choledochal cysts(CC’s).METHODS:Between 2009 and 2012,patients who underwent MRCP for perioperative... AIM:To determine the merits of magnetic resonance cholangiopancreatography(MRCP) as the primary diagnostic test for choledochal cysts(CC’s).METHODS:Between 2009 and 2012,patients who underwent MRCP for perioperative diagnosis were identified.Demographic information,clinical characteristics,and radiographic findings were recorded.MRCP results were compared with intraoperative findings.A PubMed search identified studies published between 1996-2012,employing MRCP as the primary preoperative imaging and comparing results with either endoscopic retrograde cholangiopancreatography(ERCP) or operative findings.Detection rates for CC’s and abnormal pancreaticobiliary junction(APBJ) were calculated.In addition detection rates for clinically related biliary pathology like choledocholithiasis and cholangiocarcinomas in patients diagnosed with CC’s were also evaluated.RESULTS:Eight patients were identified with CC’s.Six patients out of them had typeⅣCC’s,1 had type I and 1 had a new variant of choledochal cyst with confluent dilatation of the common bile duct(CBD) and cystic duct.Seven patients had an APBJ and 3 of those had a long common-channel.Gallstones were found in 2 patients,1 had a CBD stone,and 1 pancreatic-duct stone was also detected.In all cases,MRCP successfully identified the type of CC’s,as well as APBJ with ductal stones.From analyzing the literature,we found that MRCP has 96%-100% detection rate for CC’s.Additionally,we found that the range for sensitivity,specificity,and diagnostic accuracy was 53%-100%,90%-100% and 56%-100% in diagnosing APBJ.MRCP’s detection rate was 100% for choledocholithiasis and 87% for cholangiocarcinomas with concurrent CC’s.CONCLUSION:After initial ultrasound and computed tomography scan,MRCP should be the next diagnostic test in both adult and pediatric patients.ERCP should be reserved for patients where therapeutic intervention is needed.展开更多
基金Supported by The Association for International Cancer Research(AICRto Dr.Al-Hassi HO)+6 种基金ScotlandFunded by the AICRgrant No.120234a BBSRC Strategic Research Grant(to English N and Knight SCWMNIP33458)the St Mark’s Hospital FoundationUnited Kingdom
文摘Inflammatory bowel diseases are characterised by inflammation that compromises the integrity of the epithelial barrier. The intestinal epithelium is not only a static barrier but has evolved complex mechanisms to control and regulate bacterial interactions with the mucosal surface. Apical tight junction proteins are critical in the maintenance of epithelial barrier function and control of paracellular permeability. The characterisation of alterations in tight junction proteins as key players in epithelial barrier function in inflammatory bowel diseases is rapidly enhancing our understanding of critical mechanisms in disease pathogenesis as well as novel therapeutic opportunities. Here we give an overview of recent literature focusing on the role of tight junction proteins, in particular claudins, in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer.
文摘Background： Leakage of the intestinal mucosal barrier may cause translocation of bacteria, then leading to multiorgan lhilure. This study hypothesized that rhubarb monomers might protect the gut mucosal barrier in sepsis through junction proteins. Methods： Healthy male Sprague-Dawley rats （weighing 230-250 g） tinder anesthesia and sedation were subjected to cecal ligation and perforation （CLP）. After surgical preparation, rats were randornly assigned to eight groups （n = 6 or 8 each group）： sham group （Group A： normal saline gavage）; sepsis group （Group B： nomlal saline gavage）; Group C （intraperitoneally, dexamethasone 0.5 mg/kg） immediately after CLP surgery; and rhubarb monomer （ 100 mg/kg in normal saline）-treated groups （Group D： rhein： Group E： emodin; Group F： 3,8-dihydroxy- l-methyl-anthraquinone-2-carboxylic acid; Group G： 1-O-caffeoyl-2-（4-hydroxy-O-cinnamoyl）-D-glucose; and Group H： daucosterol linoleate）. Animals were sacrificed after 24 h. Intestinal histology, lactulose, mannito[ concentrations were measured, and zonula occludens （ZO）-I, occludin and claudin-5 transcription （polymerase chain reaction）, translation （by Western blot analysis）, and expression （by immunohistochemistry） were also measured. Results： Intestinal histology revealed injury to intestinal mucosal villi induced by sepsis in Group B, compared with Group A. Compared with Group A （0.17 ± 0.41 ）, the pathological scores in Groups B （2.83 ± 0.41, P 〈 0.001）, C （ 1.83 ± 0.41, P 〈 0.001 ）, D （2.00 ± 0.63, P 〈 0.001）, E （ 1.83 ± 0.41, P 〈 0.001 ）, F （ 1.83 ± 0.75, P 〈 0.001 ）, G （2.17 ± 0.41, P 〈 0.001 ）,and H （ 1.83 ± 0.41, P 〈 0.001 ） were significantly increased. Lactulose/mannitol （L/M） ratio in Group B （0.046 ± 0.003） was significantly higher than in Group A （0.013 ± 0.001, P 〈 0.001） while L/M ratios in Groups C （0.028 ± 0.002, P 〈 0.001 ）, D （0.029 ± 0.003, P 〈 0.001 ）, E
基金supported by the National Natural Science Foundation of China(General Program),No.81771271(to JF)
文摘Constraint-induced movement therapy after cerebral ischemia stimulates axonal growth by decreasing expression levels of Nogo-A,RhoA,and Rho-associated kinase(ROCK)in the ischemic boundary zone.However,it remains unclear if there are any associations between the Nogo-A/RhoA/ROCK pathway and angiogenesis in adult rat brains in pathological processes such as ischemic stroke.In addition,it has not yet been reported whether constraint-induced movement therapy can promote angiogenesis in stroke in adult rats by overcoming Nogo-A/RhoA/ROCK signaling.Here,a stroke model was established by middle cerebral artery occlusion and reperfusion.Seven days after stroke,the following treatments were initiated and continued for 3 weeks:forced limb use in constraint-induced movement therapy rats(constraint-induced movement therapy group),intraperitoneal infusion of fasudil(a ROCK inhibitor)in fasudil rats(fasudil group),or lateral ventricular injection of NEP1-40(a specific antagonist of the Nogo-66 receptor)in NEP1-40 rats(NEP1-40 group).Immunohistochemistry and western blot assay results showed that,at 2 weeks after middle cerebral artery occlusion,expression levels of RhoA and ROCK were lower in the ischemic boundary zone in rats treated with NEP1-40 compared with rats treated with ischemia/reperfusion or constraint-induced movement therapy alone.However,at 4 weeks after middle cerebral artery occlusion,expression levels of RhoA and ROCK in the ischemic boundary zone were markedly decreased in the NEP1-40 and constraint-induced movement therapy groups,but there was no difference between these two groups.Compared with the ischemia/reperfusion group,modified neurological severity scores and foot fault scores were lower and time taken to locate the platform was shorter in the constraint-induced movement therapy and fasudil groups at 4 weeks after middle cerebral artery occlusion,especially in the constraint-induced movement therapy group.Immunofluorescent staining demonstrated that fasudil promoted an immune response of nerve-regene
基金financially supported by China Agriculture Research System (CARS-36) (2013B060400039 to 2011A020102009)National Basic Research Program of China (2013CB127301, and 2013CB127304)+1 种基金Science and Technology Planning Project of Guangdong Province (2013B060400039,2013A061401020)Special Program for Guangdong Research Institutions' Innovation and Construction(2012B060600005)
文摘This study examined effects of dietary protein sources and levels on intestinal health of 21 to 35 d-old weaned piglets fed antibiotics-free diets. A total of 150 weaned piglets(21 d of age) were allotted to 5 dietary treatment groups. Diets were formulated, based on corn-soybean meal, with different protein sources(fish meal and soy protein concentrate) to provide different dietary CP levels. Piglets within 5 dietary treatments were fed diets as follows, respectively: 1) control diet of 17% CP(control); 2) 19% CP diets formulated with more soy protein concentrate(SPC19); 3) fish meal(FM19); 4) 23.7% CP diets formulated with more soy protein concentrate(SPC23); 5) fish meal(FM23). The results showed that piglets from control group had higher ADG and lower incidence of diarrhea compared with those of other groups(P < 0.05). The incidence of diarrhea of piglets in FM19 group was lower than those from SPC23 group and FM23 group(P < 0.05). With the higher CP levels, villous height and villous height to crypt depth ratio of piglets in the duodenum and jejunum were decreased(P < 0.05), but crypt depth was increased(P < 0.05). Comparing control group and other groups, we found the expression of inflammatory cytokines interleukin-1β(IL-1β) and interferon-γ(IFN-γ) were increased(P < 0.05) in the jejunum and colon of piglets, as did cystic fibrosis transmembrane conductance regulators(CFTR) in the distal colon. The relative transcript abundance of Zonula occludens-1(ZO-1) in the jejunum, and occludin in the jejunum and ileum of piglets fed 23.7% CP diets were reduced compared with those fed control diet(P < 0.05). In conclusion, the 17% CP diet without in-feed antibiotics helped improve growth performance and relief of diarrhea of 21 to 35 d-old weaned piglets. Dietary CP level, rather than its source(either fish meal or soy protein concentrate), has more significant impacts on the growth performance and intestinal health of 21 to 35 d-old weaned piglets when fed antibiotics-free diets.
基金Financial supports for this work, provided by the Major Program of the National Natural Science Foundation of China (No.50490270)the National Basic Research Program of China (973) (No. 2006CB202200) the Innovation Term Project of Ministry of Education of China (No.IRT0656), are gratefully acknowledged
文摘The FLAC3D software was used to simulate and analyze numerically the displacement, stress and plastic zone distribu-tion characteristics of a large span intersection in a deep soft rock roadway after the surrounding rock was excavated. Our simula-tion results show that there are two kinds of dominating factors affecting roadway stability at points of intersection, one is the angle between horizontal stress and axial direction of the roadway and the other are the angles at the points of intersection. These results are based on a study we carried out as follows: first, we analyzed the failure mechanism of a large span intersection and then we built a mechanical model of a rock pillar at one of the points of intersection. At the end of this analysis, we obtained the failure characteristics of the critical parts on the large span intersection. Given these failure characteristics, we proposed a new supporting method, i.e., a Double-Bolt Control Technology (DBCT). By way of numerical simulation, DBCT can effectively control the deformation of the surrounding rock at the points of intersection in roadways.
基金supported by the National Natural Science Foundation of China,No.81330029,81671380the Natural Science Foundation of Tianjin City of China,No.17JCZDJC35900
文摘Traumatic brain injury induces potent inflammatory responses that can exacerbate secondary blood-brain barrier（BBB） disruption, neuronal injury, and neurological dysfunction. Dexmedetomidine is a novel α2-adrenergic receptor agonist that exert protective effects in various central nervous system diseases. The present study was designed to investigate the neuroprotective action of dexmedetomidine in a mouse traumatic brain injury model, and to explore the possible mechanisms. Adult male C57 BL/6 J mice were subjected to controlled cortical impact. After injury, animals received 3 days of consecutive dexmedetomidine therapy（25 μg/kg per day）. The modified neurological severity score was used to assess neurological deficits. The rotarod test was used to evaluate accurate motor coordination and balance. Immunofluorescence was used to determine expression of ionized calcium binding adapter molecule-1, myeloperoxidase, and zonula occluden-1 at the injury site. An enzyme linked immunosorbent assay was used to measure the concentration of interleukin-1β（IL-1β）, tumor necrosis factor α, and IL-6. The dry-wet weight method was used to measure brain water content. The Evans blue dye extravasation assay was used to measure BBB disruption. Western blot assay was used to measure protein expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3（NLRP3）, caspase-1 p20, IL-1β, nuclear factor kappa B（NF-κB） p65, occluding, and zonula occluden-1. Flow cytometry was used to measure cellular apoptosis. Results showed that dexmedetomidine treatment attenuated early neurological dysfunction and brain edema. Further, dexmedetomidine attenuated post-traumatic inflammation, up-regulated tight junction protein expression, and reduced secondary BBB damage and apoptosis. These protective effects were accompanied by down-regulation of the NF-κB and NLRP3 inflammasome pathways. These findings suggest that dexmedetomidine exhibits neuroprotective effects against acute（3 d
文摘Esophageal motility abnormalities are among the main factors implicated in the pathogenesis of gastroesophageal reflux disease. The recent introduction in clinical and research practice of novel esophageal testing has markedly improved our understanding of the mechanisms contributing to the development of gastroesophageal reflux disease, allowing a better management of patients with this disorder. In this context, the present article intends to provide an overview of the current literature about esophageal motility dysfunctions in patients with gastroesophageal reflux disease. Esophageal manometry, by recording intraluminal pressure, represents the gold standard to diagnose esophagealmotility abnormalities. In particular, using novel techniques, such as high resolution manometry with or without concurrent intraluminal impedance monitoring, transient lower esophageal sphincter (LES) relaxations, hypotensive LES, ineffective esophageal peristalsis and bolus transit abnormalities have been better defined and strongly implicated in gastroesophageal reflux disease development. Overall, recent findings suggest that esophageal motility abnormalities are increasingly prevalent with increasing severity of reflux disease, from nonerosive reflux disease to erosive reflux disease and Barrett's esophagus. Characterizing esophageal dysmotility among different subgroups of patients with reflux disease may represent a fundamental approach to properly diagnose these patients and, thus, to set up the best therapeutic management. Currently, surgery represents the only reliable way to restore the esophagogastric junction integrity and to reduce transient LES relaxations that are considered to be the predominant mechanism by which gastric contents can enter the esophagus. On that ground, more in depth future studies assessing the pathogenetic role of dysmotility in patients with reflux disease are warranted.
基金supported by grants from the National Natural Science Foundation of ChinaNo.8117111281371272 to MCL
文摘Brain microvascular endothelial cells form the interface between nervous tissue and circulating blood, and regulate central nervous system homeostasis. Brain microvascular endothelial cells differ from peripheral endothelial cells with regards expression of specific ion transporters and receptors, and contain fewer fenestrations and pinocytotic vesicles. Brain microvascular endothelial cells also synthesize several factors that influence blood vessel function. This review describes the morphological characteristics and functions of brain microvascular endothelial cells, and summarizes current knowledge regarding changes in brain microvascular endothelial cells during stroke progression and therapies. Future studies should focus on identifying mechanisms underlying such changes and developing possible neuroprotective therapeutic interventions.
基金Supported by The National Basic Research Program of China,973 Program,Grant No.2012CB518101
文摘AIM:To investigate whether electroacupuncture(EA)at Zusanli(ST36)prevents intestinal barrier and remote organ dysfunction following prolonged hemorrhagic shock through a vagus anti-inflammatory mechanism.METHODS:Sprague-Dawley rats were subjected to about 45%of total blood volume loss followed by delayed fluid replacement(DFR)with Ringer lactate 3h after hemorrhage.In a first study,rats were randomly divided into six groups:(1)EAN:EA at non-channel acupoints followed by DFR;(2)EA:EA at ST36 after hemorrhage followed by DFR;(3)VGX/EA:vagotomy(VGX)before EA at ST36 and DFR;(4)VGX/EAN:VGX before EAN and DFR;(5)α-bungarotoxin(α-BGT)/EA:intraperitoneal injection ofα-BGT before hemorrhage,followed by EA at ST36 and DFR;and(6)α-BGT/EAN group:α-BGT injection before hemorrhage followed by EAN and DFR.Survival and mean arterial pressure(MAP)were monitored over the next 12 h.In a second study,with the same grouping and treatment,cytokine levels in plasma and intestine,organ parameters,gut injury score,gut permeability to 4 kDa FITC-dextran,and expression and distribution of tight junction protein ZO-1 were evaluated.RESULTS:MAP was significantly lowered after blood loss;EA at ST36 improved the blood pressure at corresponding time points 3 and 12 h after hemorrhage.EA at ST36 reduced tumor necrosis factor-αand interleukin(IL)-6 levels in both plasma and intestine homogenates after blood loss and DFR,while vagotomy or intraperitoneal injection ofα-BGT before EA at ST36reversed its anti-inflammatory effects,and EA at ST36did not influence IL-10 levels in plasma and intestine.EA at ST36 alleviated the injury of intestinal villus,the gut injury score being significantly lower than that of EAN group(1.85±0.33 vs 3.78±0.59,P<0.05).EA at ST36 decreased intestinal permeability to FITCdextran compared with EAN group(856.95 ng/mL±90.65 ng/mL vs 2305.62 ng/mL±278.32 ng/mL,P<0.05).EA at ST36 significantly preserved ZO-1 protein expression and localization at 12 h after hemorrhage.However,EA at non-channel acupoints had no suc
基金Supported by Natural Science Foundation of China,No.81270448 and No.81470890
文摘AIM: To assess the impact of Arpin protein and tight junction(TJ) proteins in the intestinal mucosa onbacterial translocation in patients with severe acute pancreatitis(SAP).METHODS: Fifty SAP patients were identified as study objects and then classified into two groups according to the presence of bacterial translocation(BT) in the blood [i.e., BT(+) and BT(-)].Twenty healthy individuals were included in the control group.BT was analyzed by polymerase chain reaction, colonic mucosal tissue was obtained by endoscopy and the expression of TJ proteins and Arpin protein was determined using immunofluorescence and western blotting.RESULTS: Bacterial DNA was detected in the peripheral blood of 62.0% of patients(31/50) with SAP.The expression of TJ proteins in SAP patients was lower than that in healthy controls.In contrast, Arpin protein expression in SAP patients was higher than in healthy controls(0.38 ± 0.19 vs 0.28 ± 0.16, P < 0.05).Among SAP patients, those positive for BT showed a higher level of claudin-2 expression(0.64 ± 0.27 vs 0.32 ± 0.21, P < 0.05) and a lower level of occludin(OC)(0.61 ± 0.28 vs 0.73 ± 0.32, P < 0.05) and zonula occludens-1(0.42 ± 0.26 vs 0.58 ± 0.17, P = 0.038) expression in comparison with BT(-) patients.Moreover, the level of Arpin expression in BT(+) patients was higher than in BT(-) patients(0.61 ± 0.28 vs 0.31 ± 0.24, P < 0.05).CONCLUSION: Arpin protein affects the expression of tight junction proteins and may have an impact on BT.These results contribute to a better understanding of the factors involved in bacterial translocation during acute pancreatitis.
文摘AIM To determine the optimal treatment strategy for Siewert type Ⅱ and?Ⅲ?adenocarcinoma of the esophagogastric junction.METHODS We retrospectively reviewed the medical records of 83 patients with Siewert type?Ⅱ?and?Ⅲ?adenocarcinoma of the esophagogastric junction and calculated both an index of estimated benefit from lymph node dissection for each lymph node(LN) station and a lymph node ratio(LNR: ratio of number of positive lymph nodes to the total number of dissected lymph nodes). We used Cox proportional hazard models to clarify independent poor prognostic factors. The median duration of observation was 73 mo.RESULTS Indices of estimated benefit from LN dissection were as follows, in descending order: lymph nodes(LN) along the lesser curvature, 26.5; right paracardial LN, 22.8; left paracardial LN, 11.6; LN along the left gastric artery, 10.6. The 5-year overall survival(OS) rate was 58%. Cox regression analysis revealed that vigorous venous invasion(v2, v3)(HR = 5.99; 95%CI: 1.71-24.90) and LNR of > 0.16(HR = 4.29, 95%CI: 1.79-10.89) were independent poor prognostic factors for OS.CONCLUSION LN along the lesser curvature, right and left paracardial LN, and LN along the left gastric artery should be dissected in patients with Siewert type?Ⅱ?or?Ⅲ?adenoca rcinoma of the esophagogastric junction. Patients with vigorous venous invasion and LNR of > 0.16 should be treated with aggressive adjuvant chemotherapy to improve survival outcomes.
基金supported by the National Natural Science Foundation of China (Grant No.10572143)
文摘The oil / water two-phase flow inside T-junctions was numerically simulated with a 3-D two-fluid model, and the turbulence was described using the mixture k- ε model. Some experiments of oil / water flow inside a single T-junction were conducted in the laboratory. The results show that the separating performance of T-junction largely depends on the inlet volumetric fraction and flow patterns. A reasonable agreement is reached between the numerical simulation and the experiments for both the oil fraction distribution and the separation efficiency.
基金National Natural Science Foundation of China (No. 81372344 and 81301866)New Century Excellent Talents in University support program, Ministry of Education of China (2012SCU-NCET-11-0343)
文摘Based on Siewert classification, adenocarcinomas of the esophagogastric junction （AEGs） have different behaviors of perigastric-mediastinal nodal metastasis. Siewert type I AEGs have higher incidence of mediastinal nodal metastasis than those of type H or III, especially at middle-upper mediastinum. With regard to the necessity of mediastinal lymphadenectomy, theoretically, transthoracic esophagogastrectomy with complete mediastinal lymphadenectomy is suggested for Siewert type I AEGs, while transhiatal total gastrectomy with lower mediastinal and D2 perigastric lymphadenectomy is a standard surgery for type II-III AEGs. Nevertheless, the mediastinal nodal metastasis is an independent factor of poor prognosis for any type of AEG.
基金supported by the National Natural Science Foundation of China(81471871,81772081).
文摘Severe burn injury is often accompanied by intestinal barrier dysfunction,which is closely associated with post-burn shock,bacterial translocation,systemic inflammatory response syndrome,hypercatabolism,sepsis,multiple organ dysfunction syndrome,and other complications.The intestinal epithelium forms a physical barrier that separates the intestinal lumen from the internal milieu,in which the tight junction plays a principal role.It has been well documented that after severe burn injury,many factors such as stress,ischemia/hypoxia,proinflammatory cytokines,and endotoxins can induce intestinal barrier dysfunction via multiple signaling pathways.Recent advances have provided new insights into the mechanisms and the therapeutic strategies of intestinal epithelial barrier dysfunction associated with severe burn injury.In this review,we will describe the current knowledge of the mechanisms involved in intestinal barrier dysfunction in response to severe burn injury and the emerging therapies for treating intestinal barrier dysfunction following severe burn injury.
文摘 AIM:To determine the merits of magnetic resonance cholangiopancreatography(MRCP) as the primary diagnostic test for choledochal cysts(CC’s).METHODS:Between 2009 and 2012,patients who underwent MRCP for perioperative diagnosis were identified.Demographic information,clinical characteristics,and radiographic findings were recorded.MRCP results were compared with intraoperative findings.A PubMed search identified studies published between 1996-2012,employing MRCP as the primary preoperative imaging and comparing results with either endoscopic retrograde cholangiopancreatography(ERCP) or operative findings.Detection rates for CC’s and abnormal pancreaticobiliary junction(APBJ) were calculated.In addition detection rates for clinically related biliary pathology like choledocholithiasis and cholangiocarcinomas in patients diagnosed with CC’s were also evaluated.RESULTS:Eight patients were identified with CC’s.Six patients out of them had typeⅣCC’s,1 had type I and 1 had a new variant of choledochal cyst with confluent dilatation of the common bile duct(CBD) and cystic duct.Seven patients had an APBJ and 3 of those had a long common-channel.Gallstones were found in 2 patients,1 had a CBD stone,and 1 pancreatic-duct stone was also detected.In all cases,MRCP successfully identified the type of CC’s,as well as APBJ with ductal stones.From analyzing the literature,we found that MRCP has 96%-100% detection rate for CC’s.Additionally,we found that the range for sensitivity,specificity,and diagnostic accuracy was 53%-100%,90%-100% and 56%-100% in diagnosing APBJ.MRCP’s detection rate was 100% for choledocholithiasis and 87% for cholangiocarcinomas with concurrent CC’s.CONCLUSION:After initial ultrasound and computed tomography scan,MRCP should be the next diagnostic test in both adult and pediatric patients.ERCP should be reserved for patients where therapeutic intervention is needed.
