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Objective:To investigate the protective role of Yes-associated protein(YAP)in intestinal epithelial barrier injury.Methods:The intestinal epithelial barrier model was established by culturing human colorectal adenocarcinoma cell line Caco-2 cells, which were divided into four groups: control group, Caco-2 monolayers did not receive any treatment; recombinant human tumor necrosis factor-α(rhTNF-α)group, 100 μg/L of rhTNF-α was added to Caco-2 monolayers; vector+ rhTNF-α group, Caco-2 monolayers were first added with control plasmid pcDNA3.1-vector, and 100 μg/L rhTNF-α was added 24 hours later; YAP+ rhTNF-α group, Caco-2 cells with barrier construction were first added with pcDNA3.1-YAP, and 100 μg/L rhTNF-α was added 24 hours later.Realtime-PCR and Western blot were used to evaluate YAP mRNA and protein expression level.Epithelial permeability was assayed by trans-epithelial electrical resistance(TEER)and fluorescein isothiocyanate-dextran 40(FD-40 flu). Cellular distribution of F-actin was assayed by immunofluorescence staining.Results:Compared with control group[(607.3±29.3)Ω·cm 2], TEER of rhTNF-α group[(265.3±32.7)Ω·cm 2] decreased, while TEER of YAP+ rhTNF-α group[(387.0±18.7)Ω·cm 2]increased compared with rhTNF-α group, the differences were statistically significant( P<0.001). The FD-40 flux of rhTNF-α(22.7%±0.5%) group was higher than that of the control group(6.3%±0.9%), while the FD-40 flux of Yap + rhTNF-α group(12.2%±0.8%) was lower than that of rhTNF-α group, the differences were statistically significant( P<0.001). Immunofluorescence staining showed that compared with the control group, the cytoskeletal F-actin fiber dense spot decreased in rhTNF-α group, and some cells showed obvious trans-cellular stress fiber structure, while the peripheral actin band was clear in YAP+ rhTNF-α group, and the intracellular stress fiber decreased.YAP+ TNF-α group appeared as a clear, peripheral actin ribbon with a decrease in cytoplasmic stress fibres. Conclusion:YAP overexpression significantly inhibits TNF-α induced decline of TEER, and increases of FD-40 flux and F-actin rearrangement of Caco-2.YAP could ameliorate TNF-α induced intestinal epithelial barrier injury by regulating cytoskeleton F-actin.
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Acute severe ulcerative colitis (ASUC) is one emergency in pediatric gastroenterology.The disease is serious, which may even endanger the life of patients.Close monitoring and timely pharmacological and surgical interventions are key measures to improve outcomes.Treatment methods for ASUC include necessary nutritional support, water and electrolyte disturbance correction, and possible concurrent bacterial or viral infection elimination.Patients at high risk require subcutaneous injections of low molecular weight heparin to prevent thrombosis.Intravenous cortico-steroids are the first-line treatment of ASUC.For patients showing insufficient response to corticosteroids after 3-5 days, rescue treatment with immunosuppressants or biological agents is needed.Meanwhile, the clinical symptoms, serum inflammatory indicators and albumin levels of the patients should be closely monitored.Patients who failed medical treatment should undergo timely colectomy to prevent serious complications.In this paper, a systematic review of literature and expert consensus was conducted to summarize the clinical evaluation and treatment methods of ASUC children at different stages, in order to standardize the clinical treatment of pediatric ASUC.
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Inflammatory bowel disease (IBD) is characterized by chronic relapsing intestinal inflammation which caused by genetic and environmental factors.With the research on the pathogenesis of IBD, current studies show that pyroptosis may be involved in the development of IBD.As an essential part of programmed cell death, pyroptosis is an inflammatory response that is elicited upon infection by intracellular pathogens.Activated inflammatory caspases will induce pyroptosis.According to the role of Caspase in programmed cell death, it can be divided into Caspase-1-dependent canonical pathway and Caspase-4/5/11-dependent non-canonical pathway.Activated inflammatory caspases cleave the pore-forming effector protein, gasdermin-D, inducing osmotic pressure deregulation of internal fluids and subsequently rupturing the cell membranes.Pyroptosis may be a potential therapeutic target for IBD in the future.This review described the mechanism of pyroptosis and therapeutic strategies for IBD.
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Objective:To investigate the protective role of YAP in TNF-α induced intestinal epithelial barrier injury.Methods:Caco-2 cells was cultured 14d to establish the intestinal mucosal barrier model, and then they were transfected with YAP plasmid and control plasmid vector, and 24h later they were exposed to TNF-α, and 48h later cell viability was quantified by CCK-8 assays.Cell cycle was determined by flow cytometric analysis.Cell migration was monitored by Transwell.Results:Compared to the normal control group, after exposed to TNF-α, the growth rate of Caco-2 cells was significantly decreased, and the ratio of G0/G1 phase cells was significantly higher, while the S phase and G2/M phase proportion decreased, and markedly reduced cells proliferation.The over expression of YAP significantly ameliorated the decrease of the growth rate induced by TNF-α, and promoted the cell cycle in G0/G1 phase to S phase and G2/M phase transition.Transwell results showed that the number of cell migration in control group was(172.4±13.1), after adding TNF-α stimulation decreased significantly(80.4±9.3), while the number of cell migration induced by transfection of YAP was(124.2±9.2). The difference was statistically significant( P<0.01). Conclusion:YAP inhibits intestinal epithelial barrier injury induced by TNF-α through regulating intestinal epithelial cell survival and migration.
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Objective:To investigate the role and mechanism of anterior gradient-2(AGR2)in intestinal mucosal barrier injury induced by tumor necrosis factor-α(TNF-α).Methods:Caco-2 cell monolayers were pre-transfected with an AGR2 plasmid and then exposed to TNF-α.Real-time PCR was employed to detect AGR2 mRNA expression, with western blot detection of AGR2 protein expression.Epithelial permeability was assessed by detecting transepithelial electrical resistance.Electron microscope was used to observe autophagic bodies.Results:Both AGR2 mRNA and protein expression levels were significantly reduced by TNF-α exposure compared with the levels in untreated control monolayers.AGR2 overexpression signifcantly ameliorated TNF-α induced epithelial barrier hyperpermeability, and mediated mitophagy in Caco-2 cell monolayers.Conclusion:This study suggested that AGR2 could inhibit TNF-α induced intestinal barrier dysfunction and this protective mechanism might be promoted by mediated mitophagy in Caco-2 cell monolayers.
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Objective To observe the effect of early enteral nutrition (EEN) on nutritional indicators and clinical outcomes in patients with severe heart failure undergoing mechanical ventilation. Methods Thirty-four patients with severe heart failure (grade Ⅲ-Ⅳ of cardiac function) and pulmonary infections undergoing mechanical ventilation admitted to intensive care unit (ICU) of Second Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine from May 2017 to April 2018 were enrolled. They were randomly divided into EEN group and delayed enteral nutrition (DEN) group. Both groups were given routine treatment, including mechanical ventilation, improvement of cardiac function, anti-infection, protection of vital organ function, regulation of blood sugar and adjustment of electrolyte and acid-base balance. The patients in EEN group received enteral nutrition (EN) within 48 hours after ICU admission, and in DEN group, EN was started after the patients had spent the early stage of stress and had stable vital signs (48 hours after ICU admission). The changes in serum B-type natriuretic peptide (BNP), C-reactive protein (CRP), nutritional indicators and liver function indicators at ICU admission and 7 days after treatment were compared between the two groups. The time needed for patients to reach EN target, duration of mechanical ventilation, length of ICU stay, and the 28-day mortality were recorded, and complications were observed. Results There was no significant difference in serum BNP, CRP, nutritional indicators or liver function indicators at ICU admission between the two groups. After treatment for 7 days, BNP and CRP in both groups were decreased significantly as compared with those at ICU admission [BNP (ng/L): 592.1±370.9 vs. 2 517.7±1 163.4 in EEN group, 621.9±418.8 vs. 2 251.5±1 006.8 in DEN group; CRP (mg/L): 46.0±19.6 vs. 59.8±22.5 in EEN group, 40.5±18.8 vs. 61.2±24.6 in DEN group, all P < 0.05], pre-albumin (PA) and transferrin (TF) were significantly increased [PA (g/L): 0.18±0.05 vs. 0.15±0.06 in EEN group, 0.17±0.04 vs. 0.12±0.06 in DEN group; TF (g/L): 1.6±0.4 vs. 1.5±0.4 in EEN group, 1.7±0.5 vs. 1.4±0.5 in DEN group, all P < 0.05]. However, there was no significant difference in the above indicators after treatment between the two groups (all P > 0.05). There was no significant change in liver function after treatment in both groups. The EN treatment was successfully completed in both groups. Some patients developed abdominal distension and diarrhea in varying degrees, which were alleviated by slowing down the infusion rate, supplemented by gastrointestinal motility drugs and intestinal flora adjustment drugs. The time needed to reach EN target in EEN group was significantly earlier than that in DEN group (hours: 42.4±10.2 vs. 53.8±17.1, P < 0.05), the duration of mechanical ventilation (days: 14.2±8.7 vs. 13.4±7.9), the length of ICU stay (days: 17.8±6.7 vs. 18.3±5.6) and 28-day mortality [5.9% (1/17) vs. 11.8% (2/17)] showed no significant difference as compared with those in DEN group (all P > 0.05), and it did not increase the incidence of aspiration pneumonia [23.5% (4/17) vs. 17.7% (3/17), P > 0.05]. Conclusion EEN could help to achieve nutritional goals as soon as possible, improve the nutritional status of the body, and provide conditions and basis for further treatment of severe heart failure patients.
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Objective To determine the efficacy of different first-line regimens for Helicobacter pylori(Hp) eradication,and to suggest an alternative first-line therapy particularly in children.Methods One hundred and twenty-four patients who diagnosed as peptic ulcer or chronic gastritis by gastroscope with Hp infection were included and randomly divided into four groups,each receiving different first-line eradication therapy.A group:standard triple therapy for 10 days;B group:standard triple therapy for 14 days;C group:triple therapy containing bismuth agent;D group:sequential therapy.The eradication rates of Hp and adverse event rates in four groups were compared.Results The highest eradication rate was in D group (90.9％,P ＜ 0.05),there was no significant difference between the other three groups (P ＞ 0.05).The main adverse reactions during treatment were abdominal pain,fullness,nausea and vomiting.Among them,adverse event rate was the highest in C group (41.4％,P ＜ 0.05),there was no significant difference between the other three groups (P ＞ 0.05).Conclusion The sequential therapy is significantly more effective than standard triple therapy and triple therapy containing bismuth agent.Adverse event rate is the highest in the triple therapy containing bismuth agent.
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The intestinal epithelial barrier has evolved to maintain a delicate balance between absorb-ing essential nutrients while preventing the translocation of intestinal microbiota,which contribute to inflam-mation occurence. In inflammatory bowel disease (IBD),disruptions of intestinal barrier result in increased intestinal permeability which promotes the exposition to luminal content and triggers an immunological re-sponse that promotes intestinal inflammation. IBD patients demonstrate increased intestinal paracellular per-meability. Therefore,therapeutic target to restore the mucosal barrier may provide effective therapeutic and preventive approaches against IBD. This review examines the roles of the intestinal mucosal barrier on mecha-nisms underlying mucosal barrier dysfunction in IBD.
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Objective To compare serum zinc and immunoglobulin levels between young children with diarrhea and healthy children at the same age,and discuss the correlation between serum zinc level and the disease course and immune level of diarrhea. Methods This study was carried out at the Shengjing Hospital of China Medical University between December 2012 and December 2013. A total of 150 young children with diarrhea and 427 healthy children (control group) were included,and the young children with diarrhea were divided into acute diarrhea group(n=90) and chronic diarrhea group(n=60).Zinc levels for all subjects were measured using a flame atomic absorption spectrophotometer.Results Mean serum zinc levels in the acute diarrhea group and chronic diarrhea group were significantly lower than those in the control group (P<0.01).There was no significant difference in serum zinc levels between the acute diarrhea group and chronic diarrhea group(P>0.05).The immunoglobulin IgA,IgM and IgG in the acute diarrhea group and chronic diarrhea group were significantly lower than those in the control group (P <0.01),and the immunoglobulin IgA,IgM and IgG in the chronic diarrhea group were significantly lower than those in the acute diarrhea group(P < 0.05). There were no significant correlations between serum zinc levels and immunoglobulin levels in acute diarrhea group and chronic diarrhea group(P>0.05).Conclusion Serum zinc and immunoglobulin levels in young children with diarrhea were significantly lower than those of the same age healthy children,there was no correlation between serum zinc level and immunoglobulin level in young children with diarrhea.
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Objective To investigate the effects of sufentanil on stress hormone and hemodynamic parameters in patients with sepsis in ICU. Methods A prospective randomized controlled study was carried out to select 46 patients with sepsis admitted to the ICU of Guangzhou Red Cross Hospital from October 2014 to August 2016. The patients were randomly divided into the control group(group C), fentanyl group (group F) and sufentanil group (group S). Patients in group C were given active treatment of the primary disease, and anti-infection, nutritional support, maintenance of electrolyte balance and other comprehensive treatment. Patients in group F and group S were treated in the same way as group C, while fentanyl and sufentanil were applied separately into them. The analgesic goal was behavioral pain scale (BPS) ≤3 points. The changes of stress hormone [adrenocorticotropic hormone (ACTH), glucocorticoids (GC), norepinephrine (NE) and epinephrine (E)] and hemodynamic parameters [heart rate (HR), mean arterial pressure (MAP) and central venous pressure (CVP)] before and after treatment were compared, and adverse drug reactions were recorded. The quantitative data were compared by analysis of variance or t test, and the repeated measurement data were analyzed by repeated measures analysis of variance. The enumeration data were compared by Chi-square test or Fisher exact probability method. Results There were no significant changes in the levels of NE and E before treatment and at 2 and 6 h after the treatment in the three groups (P>0.05). Compared with before treatment, there were no significant changes in ACTH and GC levels at 2 and 6 h after treatment in group C (P>0.05), and ACTH and GC levels decreased in group F and group S at 2 and 6 h after treatment (P<0.05). Compared with group C, the levels of ACTH and GC in group F and group S were lower than those in group C at 2 and 6 h after treatment (P<0.05), but there was no significant difference between group F and group S (P>0.05). Compared with before treatment, the levels of HR were decreased at 2 and 6 h after the treatment in the three groups (P<0.05). Compared with group C, the levels of HR in group F and group S was lower than that in group C at 2 and 6 h after treatment (P<0.05), but there was no significant difference between group F and group S (P>0.05). Compared with before treatment, the levels of MAP increased in different degrees at 2 and 6 h after treatment in the three groups; Except for group F, there was significant difference between group C and group S (P<0.05). The levels of MAP in group F were lower than those in group C and group S at 2 and 6 h after treatment (P<0.05), but there was no significant difference between group S and group C (P>0.05). Conclusions Sufentanil has certain advantages in alleviating stress response in patients with sepsis in ICU. Its efficacy and safety are similar to that of fentanyl. What' more, it has more stable hemodynamics.
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Objective To study the effects of mirabilite stuck on umbilical region combined with early enteral nutrition (EEN) on gastrointestinal function and serum inflammatory mediators in patients with mechanical ventilation. Methods Sixty-four patients with mechanical ventilation admitted to the Department of Intensive Care Unit of the Second Affiliated Hospital of Zhejiang Traditional Chinese Medical University from January to December 2016 were enrolled, and they were divided into an observation group and a control group by random number table, 32 cases in each group. The control group was treated with routine western medicine+ EEN, and the observation group was treated additionally with mirabilite stuck onto umbilical region on the basis of the treatment of the control group. The clinical effect was observed after 7 days of treatment. The differences in gastrointestinal function scores and the levels of serum inflammatory mediators were compared between the two groups before and after treatment.Results After treatment, gastrointestinal function scores of the diarrhea, bowel sound, abdominal distension and the levels of white blood cell count (WBC), serum procalcitonin (PCT), serum C-reactive protein (CRP) were decreased significantly in both groups compared with those before treatment, and the degrees of decreasing in above index levels after treatment in the observation group were more obvious than those in the control group [diarrhea: 0.72±0.03 vs. 1.59±0.21, bowel sounds: 0.87±0.05 vs. 1.54±0.18, abdominal distension: 0.77±0.04 vs. 1.63±0.09, WBC (×109/L): 9.87±1.25 vs. 12.46±2.04, PCT (μg/L): 5.43±1.02 vs. 9.65±1.63, CRP (mg/L): 56.87±4.52 vs. 89.43±8.24, allP < 0.05].Conclusion Applying mirabilite stuck on umbilical region combined with EEN can effectively promote the recovery of gastrointestinal function and significantly decrease the levels of serum inflammatory mediators in patients with mechanical ventilation.
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Objective To explore the efficacy and safety of plastic titanic plates internal fixation in the treatment of intra-articular calcaneus fracture.Methods 42 patients with intra-articular calcaneus fracture were selected and taken lateral calcaneal improvement “L” shaped incision for the correction of calcaneal shortening and valgus deformity.Skidmore needle went through collapse of the articular surface below from calcaneal fractures after block nodules along with bone shaft,and restored Bohler angle,Gissane angle and bone length,height,and the lateral fracture piece was reset.The fixation was taken by plastic reconstruction titanic plates,and the fracture was inspected by Xray.Results In 42 patients,the fracture healing time was (11.4 ± 0.6) weeks.The fracture position was good on the line,and the articular surface of calcaneus and talus was smooth,and the Bohler angle,Gissane angle of calcaneus were returned to normal.The excellent rate was 90.5％ by Maryland score.No surgical causes of broken plate and screw breakage were found.Conclusion Internal fixation with open reduction and plastic titanic plates internal fixation for the treatment of intra-articular calcaneal fractures has a significant effect and safety,which is worthy of promotion.
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ObjectiveTo investigate the prognostic value of fluid responsiveness in patients with acute respiratory stress syndrome (ARDS).Methods Fifty-nine mechanically ventilated patients with ARDS were enrolled.Their stroke volume variations (SVV) were detected by pulse contour continuous cardiac output (PiCCO) analysis device,and then the patients were subsequently divided into fluid responsive group (SVV≥15％) and fluid non-responsive group (SVV ＜ 15％ ).The differences in 28-day survival,length of ICU stay and duration of mechanical ventilation between the 2 groups were compared.Thereafter,the 28-day survival of patients was analyzed by Kaplain-Meier survival model and the relationship between SVV and mortality within 28 days was analyzed by logistic regression model.Results In comparison with fluid non-responsive group,the 28-day survival of fluid responsive group was significantly increased (85.3％ vs.56.0％,P =0.012),the length of ICU stay was significantly shortened [( 13.1 ±5.2 ) d vs. (21.6±9.0) d,P=0.008],and the duration of mechanical ventilation was significantly shortened as well [( 11.4 ± 5.3 ) d vs.( 18.3 ± 4.9) d,P =0.022] ; Logistic analysis revealed that SVV ＜ 15％ increased the risk of 28-day mortality ( OR =4.82 ; 95％ CI:2.67 ～ 11.71,P =0.009 ).ConclusionsSVV-based fluid responsiveness can be served as a prognostic predictor for ventilated patients with ARDS.
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ObjectiveTo explore the effect and surgical management of the internal fixation with double steel plate by the olecranon osteotomy approach in the treatment of severe condyle humeral intercondylar splintered fracture.Methods50 patients with severe condyle humeral intercondylar splintered fractures were treated by double plate internal fixation through olecranon osteotomy.ResultsAll patients(50 cases) were followed up for 6 months to 2 years.The complications such as bone defect,ossifyingmyositis,tardive ulnar nerve compression,and internal fixation fail were not found.According to Aitken Rorabeck scale,the function of the elbow showed excellent in 35 cases,good in 9 cases,fair in 6 cases,the excellent and good rate was 88％.ConclusionThe internal fixation with double steel plate by the olecranon osteotomy approach in the treatment of severe condyle humeral intercondylar splintered fracture was a good approach.Anatomical reduction surgically reconstructed stabilization of the elbow and early active rehabilitation were crucial factors of functional rehabilitation of the elbow.
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Objective To study the efficacy, safety and compliance of insulin human analog insulin aspart (NovoRapid) and insulin zinc protamine analog (Basulin) in the application on type 2 diabetes mellitus(T2DM)pafients during perioperative period. Methods Sixty T2DM patients were divided into 3 groups (n=20). Group A was treated with NovoRapid+Basulin, group B was treated with insulin human (Humulin R + Humulin N) and group C was treated with insulin pump (Humulin and NovoRapid). Blood glucose was detected in all of the patients before the meal, 2 hours after meal, before the sleep and during the operation. Results Blood glucose could all achieve the control level with the three methods of treatment. The rates of hypoglycemia in the three groups were 10%, 30% and 5% respectively, and the rates of patient satisfaction were 95%, 70% and 100% respectively. Conclusions Insulin human analog could control blood glucose effectively and safely, the compliance is also high. It is feasible of applying insulin human analog in the blood glucose control during perioperative period.
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Objective To evaluate efficacy and therapeutic satisfaction of novel analogue glargine combined with repaglinide in type 2 diabetic patients(T2DM) after switching from the most frequently used twice daily injection of premixed insulin(Humulin 70/30 30% rapid acting and 70% NPH before meals).Methods 18 patients with T2DM whose blood glucose control was poor receiving twice daily premixed insulin had been switched to receive a once daily injection of glargine together with repaglinide and biguanides(metfomin) or TZDS(reglitazone) was continued if it was taken to relieve insulin resistance.After 16 weeks the blood glucose concentrations and HbA1c levels were detected and hypoglycemia was reported.Results At the time of post-16week after the switch,fasting blood glucose access to normal;blood glucose fluctuation relieved and HbA1c levels decreased(from 7.84?0.21 to 6.52?0.13).Symptomatic hypoglycemia decreased.Conclusion These results indicate that insulin glargine combined with repaglinide can be replaced from the twice daily premixed insulin injection regiment for the T2DM even with poor glucose control.