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Surgery is an important method for the treatment of resectable esophageal cancer. With the continuous development of minimally invasive esophageal technology, video-assisted thoracoscopic esophagectomy (VATE) has demonstrated obvious advantages over conventional open surgery and has been widely accepted. However, there are still some esophageal cancer patients who cannot benefit from VATE. Inflatable video-assisted mediastinoscopic transhiatal esophagectomy(IVMTE) does not require one-lung ventilation, reduces postoperative complications, expands surgical indications, and brings surgical opportunities for patients with impaired lung function and thoracic lesions, which has become a new choice for the treatment of esophageal cancer. However, the limited field of surgical view and the tunneling surgical approach undoubtedly increase the difficulty of surgery, and how to clearly expose the anatomical structures and thoroughly dissect the lymph nodes has always been the key points and difficulties of surgery. The authors review relevant literatures to discuss the clinical progress and limitations of IVMTE.
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Objective To explore the application value of cone-shaped gastric tube combined with cervical end-to-end anastomosis in thoracoscopic and laparoscopic esophagectomy for esophageal cancer.Methods The retrospective and descriptive study was conducted.The clinical data of 122 patients with esophageal cancer who were admitted to West China Hospital of Sichuan University from December 2016 to December 2017 were collected.There were 89 males and 33 females,aged (61±8)years,with a range from 48 to 81 years.McKeowntype three-incision esophagectomy was performed,and the cone-shaped gastric tube was pulled up to esophagus in left neck for hand-sewn end-to-end anastomosis after the dissection of esophagus and stomach under total thoracoscopy and laparoscopy.Observation indicators:(1) surgical treatment situations;(2) postoperative complications;(3) follow-up.Follow-up using outpatient examination was performed to detect postoperative gastroesophageal reflux,anastomotic stenosis and evaluate anastomotic width at 1,3,6 months and one year postoperatively up to December 2018.Measurement data with normal distribution were represented by Mean±SD.Measurement data with skewed distribution were described by M (P25,P75) or M (range).Count data were expressed by absolute number.Results (1) Surgical treatment situations:122 patients underwent laparocopic McKeown-type three-incision esophagectomy successfully,using cone-shaped gastric tube combined with cervical hand-sewn end-to-end anastomosis as digestive tract reconstruction,with no intraoperative conversion to open surgery.The operation time,cervical anastomosis time,and volume of intraoperative blood loss were (229 ± 49) minutes,(27± 1) minutes,and 50 mL (40 mL,60 mL),respectively.There were 6-8 stations of lymph node dissected,and the number of lymph node dissected were 19 (15,25).Duration of postoperative hospital stay was 10 days (9 days,11 days) in the 122 patients.(2) Postoperative complications:31 of 122 patients had postoperative complications.The primary complications:3 patients with anastomotic fistula were cured by conservative treatment including enteral nutrition through placement of nutritional tube under gastroscope,closed thoracic drainage and anti-infection;6 cases with severe thoracic gastric dilation were cured after gastrointestinal decompression.The secondary complications of 22 patients included 8 cases with hoarseness caused by recurrent laryngeal never injury,5 with arrhythmia,9 with pulmonary infection.They were cured after symptomatic and supportive treatment.No chylothorax occured,and there was no perioperative death.(3) Follow-up:all the 122 patients were followed up for 10-24 months,with a median time of 19 months.During the follow-up,7 cases with anastomotic stenosis including 4 scoring less than grade 2 and 3 scoring more than grade 3 were relieved after dilation through gastroscope.There were 33 of 122 patients without any reflux symptoms,and 89 with reflux symptoms,among which 52 were scored 1,25 were scored 2 and 12 were scored 3.The width of gastroesophageal anastomosis measured by barium radiography at 1 month after operation was (1.2±0.4) cm.Conclusion Coneshaped gastric tube combined with cervical end-to-end anastomosis in digestive tract reconstruction of thoracoscopic and laparoscopic esophagectomy can reduce the incidence of postoperative anastomotic complications and thoracic gastric dilation,and nasogastric tube placement could be abandoned,which demonstrates good safety and universality.
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Objective To investigate the effects and mechanisms of glutamine (Gln) supplementation on oxidative stress,autophagy response and neurobehavioral outcome after traumatic brain injury (TBI) in rats.Methods TBI animal models were established using Feeney's method.Eighty SD rats were randomly divided into 4 groups:sham operation group (group Sham),Sham + glutamine supplementation group (group Sham+ GLN),traumatic brain injury group (group TBI),and TBI + glutamine supplementation group (group TBI+ GLN).We measured rat behavioral outcomes by modified neurologic severity score (mNSS) tests at day 1,3,7 and 14 after TBI.The apoptosis neurons in TBI cerebral cortex were determined by TUNEL staining.The expression of reactive oxygen species (ROS) was tested by ROS kits.Oxidative stress and autophagy related cytokines (HO-1,NQO1,Nrf2,LC3-Ⅱ and Beclin-1) were tested with Western blotting.Results Compared with the TBI group,the neurological function was improved [(9.79±0.43) vs.(8.43±0.30),F =6.775,P =0.010] and the apoptosis rate decreased (19.88% ± 1.60% vs.15.35% ± 1.28%,P =0.013) in the TBI+ GLN group after 7-day treatment.Compared with the Sham group,the protein expression of ROS increased (P=0.000),and the expression of anti-oxidative stress factors (HO-1,NQO1) and Nrf2 pathway significantly decreased in the TBI group.After glutamine supplementation was given,the expression of ROS decreased and the expressions of HO-1 and NQO1 increased.The Nrf2 pathway and autophagy response also were activated with the expressions of Nrf2,LC3-Ⅱ and Beclin-1 increasing.Conclusion Glutamine supplementation can markedly reduce neuron apoptosis and improve neurological outcomes after TBI,thus has the protective effect on nerves by inhibiting TBI-induced oxidative stress response,activating Nrf2 pathway and autophagy response.
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OBJECTIVE@#To investigate the inhibitory effects of silencing migration-inducing gene-7 (Mig-7) on vasculogenic mimicry formation, migration and invasion of human glioma cells and whether MEK/ERK signaling pathway mediates these effects.@*METHODS@#Human glioma U251 cells were infected by lentiviral vectors carrying a small interfering RNA targeting Mig-7 gene (sh-Mig-) or a negative control shRNA (sh-NC), and real-time quantitative PCR was used to detect the expression level of Mig- mRNA in the cells. Three-dimensional culture and Transwell chamber invasion assay were used to observe the effect of Mig- gene silencing on vasculogenic mimicry formation and invasion ability of the U251 cells. Western blotting was performed to detect the changes in the protein expression levels of MEK/ERK in the infected cells.@*RESULTS@#We successfully obtained a U251 cell line with stable low expression of Mig- gene using RNA interference technique. Compared with the cells infected with sh-NC lentivirus and the non- infected cells, U251 cells infected with the lentiviral vector carrying sh-Mig- showed significantly decreased expression level of Mig- ( < 0.01) with obviously lowered vasculogenic mimicry formation and invasion abilities ( < 0.05). Mig- silencing also significantly lowered the expressions of MEK and ERK proteins in U251 cells ( < 0.05).@*CONCLUSIONS@#Silencing of Mig-7 gene inhibits vasculogenic mimicry formation and invasion of U251 cells possibly by suppressing MEK/ERK signaling, suggesting the important role of Mig-7 gene in vasculogenic mimicry formation and invasion of human glioma cells.
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Humanos , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Silenciador del Gen , Glioma , Genética , Patología , Proteínas de Neoplasias , Metabolismo , ARN Interferente Pequeño , Transducción de SeñalRESUMEN
Esophagectomy is one of the most complex interventions in thoracic surgery.Traditional open esophagectomy requires large incision and is associated with many complications.Video-assisted thoracoscopic surgery (VATS) contributes to less complications and hospital stay,and uniportal VATS has more minimal advantages over multi-portal VATS.Due to the technical complexity of esophagectomy,uniportal VATS is highly difficult.Surgeons from Taiwan reported uniportal VATS esophagectomy for the first time in 2015,and this uniportal technique was also reported by surgeons from other institutions.Nowadays,uniportal VATS esophagectomy is still in its initial stage,skills are immature,and long-term,large sample,controlled studies are demanded.Here,authors reviewed the development,skills,short-term outcomes,current practice in West China Hospital,the advantages and challenges for unipotrtal VATS esophagectomy.
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Objective To investigate the effects of enteral immunonutrition supplemented with omega-3 polyunsaturated fatty acid (ω-3 PUFA) on inflammatory response,intestinal mucosal barrier function and the prognosis in patients with severe traumatic brain injury (sTBI).Methods 122 patients of sTBI hospitalized between January 2015 and December 2016 were randomly divided into experimental group (ω-3 PUFA,n=61) and control group (n =61).The serum levels of tumor necrosis factor-α (TNF-α),interleukin (IL)-6 and neuron specific enolase (NSE) were tested with enzyme linked immunosorbent assay.Meanwhile,D-lactate acid and intestinal fat acid binding protein (I-FABP) were evaluated by enzymology spectrophotometer method.After 14 days of treatment,the Glasgow Coma Scale (GCS) scores,Acute Physiology and Chronic Health Evaluation (APACHE) Ⅱ scores and prognoses of both groups were compared.Results The serum levels of inflammatory factors (TNF-α and IL-6),intestinal mucosal barrier function indicators (D-lactate acid and I-FABP) and NSE proteins significantly increased after sTBI (P =0.01).Compared with the control group,the experimental group on day 3 had significantly lower serum levels of inflammatory factors [TNF-α:(107.77± 19.79) μg/Lvs.(151.76±21.65) μg/L,P=0.01;IL-6:(76.85±7.15) μg/Lvs.(105.27±10.12) μg/L,P=0.01] and intestinal mucosal barrier function indicators [D-lactate:(69.81 ±6.32) μg/L vs.(89.80± 8.75) μg/L,P=0.03;I-FABP:(40.81±6.73) μg/Lvs.(56.60±8.58) μg/L,P=0.01].On day 7,the experimental group had significantly lower expression of NSE proteins than the control group [(13.63± 2.53) μg/L vs.(19.12±3.00) μg/L,P=0.02].The experimental group received better prognosis compared to the control group on day 14 [GCS scores:(9.74±0.76) vs.(8.44±0.53),P=0.04;APACHE Ⅱ scores:(14.67±1.37) vs.(17.53±1.47),P=0.03].The experimental group also had fewer days in hospitalization [(19.37±2.27) d vs.(25.42±2.61) d,P=0.01].Conclusion Enteral immunonutrition supplemented with ω-3 PUFA can effectively regulate the inflammatory response,and reduce impairment to the intestinal mucosal barrier function and damage to neurons in patients with sTBI.
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Objective To investigate the effects of enteral immunonutrition supplemented with omega-3 polyunsaturated fatty acid (ω-3 PUFA) on the incidences and severity of ventilator associated pneumonia com- plications, inflammatory response, and the prognosis in patients with severe traumatic brain injury (sTBI) un-dergoing ventilator therapy. Methods From January 2015 to June 2017, 64 patients of sTBI were selected and randomly divided into experimental group (ω-3 PUFA, n=32) and control group (n=32). White blood cells (WBC) and the proportion of neutrophils (N%) were evaluated by cell analyzer. Meanwhile, the serum levels of C-reactive protein (CRP) and procalcitonin (PCT) were tested with enzyme linked immunosorbent assay. After 14-days treatment, the Glasgow coma scale (GCS) score, APACHE Ⅱ score, clinical pulmonary infec-tion score (CPIS), pulmonary function and prognoses were also compared between the two groups. Results As compared with the control group, the experimental group had lower incidences of ventilator associated pneumonia (66% vs. 56%, P=0. 048), reduced degree of lung infection and lower CPIS (8. 25±0. 60 vs. 7. 47±0. 53); higher lung function indexes [FVC: (2. 89±0. 19) L vs. (3. 46±0. 22) L, P=0. 010;FEV1: (2. 35±0. 16) L vs. (2. 84±0. 24) L, P=0. 040; FEV1/FVC %: (49. 11±3. 34)% vs. (56. 00± 2. 64)%, P=0. 038) ]; lower serum levels of inflammatory responses [WBC: (11. 83±0. 74) ×109/L vs. (9. 51±0. 90) ×109/L, P=0. 029; N%: (79. 11±1. 51)% vs. (72. 71±1. 16)%, P=0. 041; CRP:(85. 15±8. 42) mg/L vs. (63. 96±5. 72) mg/L, P=0. 001; PCT: (6. 43±0. 47) μg/L vs. (4. 83±0. 39) μg/L, P=0. 013] 14 days after enteral immunonutrition supplemented with ω-3 PUFA. As compared with the control group, the experimental group received better prognosis with GCS scores increasing ( 8. 69 ± 0. 41 vs. 9. 52±0. 59, P=0. 038), APACHE Ⅱ scores decreasing (14. 74±1. 01 vs. 12. 68±0. 89, P=0. 049), the time of mechanical ventilation [ (13. 23±1. 17) d vs. (10. 88±1. 24) d, P=0. 024] and the hospitalization days [ (23. 29±2. 45) d vs. (18. 42±1. 96) d, P=0. 012] reduced on the 14th day, mechanical ventilation withdraw rate within 14 days increasing [24/32 (75%) vs. 27/32 (84%), P=0. 030] on the 14th day. Conclusion Enteral immunonutrition supplemented with ω-3 PUFA can effectively reduce the incidence of ventilator associated pneumonia, alleviate the degree of infection and the inflammatory response in patients with sTBI undergoing ventilator therapy possibly improving condition and prognosis, which is worthy of being widely used.
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Objective To investigate the effect of endoplasmic reticulum stress on sensitivity of glioma cell line U87 to temozolomide (TMZ) and underlying mechanism.Methods (1) Glioma U87 cells were routinely cultured for 24 h in vitro;different concentrations of TMZ (0,12.5,25,50,100 μmol/L) were added to intervene the cell proliferation of U87 cells for 24 h;MTT method was used to detect the cellular proliferation inhibition rate,and half maximal inhibitory concentration (IC50) of TMZ was calculated;tunicamycin (TM) treatment (0,2,4,8 μmol/L) was given to the cells for 6 h,and then,50 μmol/L TMZ was given for 24 h,and cellular proliferation inhibition rate of U87 was detect by MTT method.(2) U87 cells were randomly divided into control group,TM group,TMZ group and TM+TMZ group;pretreatment of TM for 6 h was given to cells from TM group and TM+TMZ group;and 50 μmol/L TMZ was given to cells from TMZ group and TM+TMZ group;same amount of medium was given to cells from control group;24 h after treatment,the apoptotic rate was examined by flow cytometry;Westem blotting was used to detect the protein expressions of caspase-3,B-cell lymphoma 2 associated X protein (Bax),O-6-methlguanine-DNA methyltransferase (MGMT),glucose-regulated protein 78 (GRP78),and inositol-requiring enzyme 1 (IRE-l).Results (1) MTT showed that IC50 of TMZ was 50 μmol/L.As compared with that of 0 μmol/L TM+50 μmol/L TMZ group or 2 μmol/L TM+50 μmol/L TMZ group,the cellular proliferation inhibition rate of 4 μmol/L TM+50 μmol/L TMZ group and 8 μmol/L TM+50 μmol/L TMZ group was significantly decreased (P<0.05).(2) As compared with TMZ group,TM+TMZ group had significantly decreased apoptotic rate (46.98%±4.79% vs.35.74% ±4.09%),significantly decreased caspase-3 and Bax protein expressions,and significantly increased MGMT,GRP78 and IRE-1 protein expressions (P<0.05).Conclusion Endoplasmic reticulum stress can increase the resistance gene MGMT expression,decrease the chemotherapy sensitivity to TMZ,and induce chemoresistance ofglioma cell line U87.
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Objective To investigate the effect ofeicosapentaenoic acid (EPA) on sensitivity of glioma cell line U87 to temozolomide (TMZ) and its underlying mechanism.Methods (1) U87 cells were routinely cultured in vitro,and 0,25,50,100 and 200 μmol/L EPA was given to these cells for 12,24,and 48 h;MTT assay was used to detect the cell viability.(2) U87 cells were randomly divided into control group,EPA group,TMZ group and EPA+TMZ group (concentrations of EPA and TMZ were 25 and 100 mol/L;EPA pretreatment for 12,24 and 48 h was given;TMZ was given for 24 h);MTT assay was used to evaluate the inhibition ratio of cell proliferation.(3) U87 cells were randomly divided into control group Ⅰ,EPA group Ⅰ,TMZ group Ⅰ and EPA+TMZ group Ⅰ (concentrations of EPA and TMZ were 25 and 100 mol/L;EPA pretreatment for 6 h was given;TMZ was given for 24 h);the apoptotic ratio was examined by fiow eytometry (FCM);Western blotting was used to detect the protein expressions ofcleavedcaspase-3,Bax,O-6-methlguanine-DNAmethyltransferase (MGMT),nuclear factor (NF)-κB signaling pathway related protein p65,and NF-κB inhibitor IKBα;immunofluorescent staining was employed to detect the MGMT and NF-κB p65 expressions;methylated specific PCR (MSP)was used to detect the MGMT gene promoter methylation.Results (1) The 50,100 and 200 μmol/L EPA caused concentration-dependent and time-dependent proliferation inhibition of U87 cells.(2) The inhibition ratio of cell proliferation in EPA+TMZ group was significantly higher as compared with that in the TMZ group (P<0.05).(3) As compared with that in the TMZ group Ⅰ (34.58%±4.35%),the apoptotic ratio of U87 cells in the EPA+TMZ group Ⅰ was significantly increased (53.28%±5.05%,P<0.05);Western blotting showed that as compared with those in TMZ group Ⅰ,the protein expressions of activated caspase-3,Bax and IKBα were significantly increased,and MGMT and NF-κB p65 protein expressions were significantly decreased in EPA+TMZ group Ⅰ (P<0.05);immunofluorescent staining indicated that the MGMT and NF-κB p65 protein expressions in EPA+TMZ group Ⅰ were significantly lower than those in TMZ group Ⅰ (P<0.05);the MGMT gene promoter methylaion in EPA+TMZ group Ⅰ was higher than that in TMZ group Ⅰ.Conclusion EPA enhances the sensitivity of glioma cell line U87 to TMZ,which may inhibit the MGMT expression by NF-κB dependent pathway.
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Objective To investigate the effect of Eicosapentaenoic scid (EPA) on the sensitivity of glioma cell line U87 to temozolomide (TMZ) and the mechanism behind this effect.Methods U87 cells were randomly divided into four groups:control group,TMZ group,EPA+TMZ group and endoplasmic reticulum stress (ERS) activation tunicamycin group (EPA+TMZ+TM group).MTT method was used to evaluate inhibition ratio of cell proliferation.The apoptotic ratio was examined by flow eytometry.Western blot was used to detect the protein expressions of apoptosis cytokines (caspase-3 and Bax) and ERS cytokines [glucose-regulated protein 78 (GRP78) and inositol-requiring enzyme 1 (IRE-1)].Results EPA causes concentration-dependent and time-dependent inhibition of the cell proliferation (all P=0.00).EPA significantly enhanced the sensitivity of glioma cell line U87 to temozolomide.Compared to TMZ treatment alone,the inhibition ratio [(56.27+6.15)% vs.(42.32±4.12)%,P=0.03] and apoptotic ratio [(49.78±5.94)% vs.(37.74± 4.24)%,P=0.04] of U87 cells were enhanced by EPA+TMZ treatment.Western blot showed that the expression of apoptotic factor caspase-3 and Bax proteins were increased by EPA+TMZ treatment,while the protein expressions of ERS-related factors (GRP78 and IRE-1) were significantly inhibited (P=0.01).However,the salutary effects of EPA were reversed by ERS activation tunicamycin.Conclusion EPA enhances the sensitivity of glioma cell line U87 to temozolomide,the mechanism of which may be the suppression of ERS response.
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Objective To investigate the effects of glutamine (Gln) supplementation on neurologica severity score,brain edema,neuron apoptosis,and endoplasmic reticulum stress (ERS) response after traumatic brain injury (TBI) in rats.Methods TBI rat models were established using modified Feeney's method.Eighty Sprague-Dawley rats were divided into 4 groups with a random number table:sham operation group (Sham group),TBI group,Gln supplementation group (TBI + Gln group) and ERS inducer 2-deoxy-D-glucose group (TBI +Gln + 2-DG group).We measured the rats' neurobehavioral outcomes by modified neurologic severity score (mNSS) on day 1,3,7 and 14 after TBI.Neuron apoptosis was detected using TUNEL staining.Brain water content was measured with wet-dry weight method.The apoptosis-related protein (caspase-12,caspase3,and Bcl-2) and ERS-related cytokines [inositol-requiring enzyme 1 (IRE-1),C/EBP homologous protein (CHOP)] expressions in TBI cerebral cortex were determined by immunohistochemistry staining and Western blot.Results Compared with the Sham group,the levels of brain edema,mNSS,apoptosis-related protein (caspase-12,caspase-3,Bcl-2) and ERS-related proteins (IRE-1,CHOP) were significantly increased in the other three groups (all P =0.00).Compared with the TB1 group,the TBI +Gln group showed significant lower brain water content [3 d:(81.39±0.59)% vs.(83.54±0.52)%,P=0.04;7 d:(74.86±0.38)% vs.(77.32±0.66)%,P=0.03],improved mNSS (8.63 ±0.22 vs.10.37±0.29,P=0.03),suppressed expressions of apoptosis-and ERS-related proteins (caspase-12,caspase-3,IRE-1,and CHOP)(P =0.01,P < 0.01),and increased expression of anti-apoptotic protein Bcl-2 (P =0.02).Compared withthe TBI + Gln group,the expression of ERS-related factors (IRE-1 and CHOP),brain edema level,and neurological severity were increased in the TBI + Glu + 2-DG group.Conclusion Glutamine supplementation may have neuroprotection function,demonstrated as reducing brain edema and neuron apoptosis,and improving neurobehaviroal outcomes after TBI,possibly mediated by inhibiting TBI-induced ERS response.
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The definition,staging and optimal treatment of adenocarcinoma of esophagogastric junction (AEG) have long been in controversy.Surgery is still the primary treatment for resectable AEG,and surgical procedures depend on its classifications.However,the efficacy of surgery alone is barely satisfactory.Neoadjuvant chemoradiotherapy and perioperative chemotherapy can improve the survival of patients.Simplified 2 cm principle is presented in the 8th edition of American Joint Committee on Cancer for TNM staging system of esophageal cancer.In addition,the new edition provides clinical staging and pathologic staging after neoadjuvant therapy,improving the clinical practicability of new staging system.
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Objective To compare and explore the optimal pathway of enteral nutrition between nasointestinal tube and nasogastric tube in patients with severe traumatic brain injury (sTBI). Methods One hunderd patients with sTBI, admitted to our hospital from January 2016 to December 2016, were divided into nasointestinal tube group and nasogastric tube group (n=50) according to different enteral nutrition pathways. The serum levels of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 were tested with enzyme linked immunosorbent assay (ELISA). Meanwhile, intestinal mucosal barrier function indexes D-lactate acid and intestinal fat acid binding protein (I-FABP) were evaluated by enzymology spectrophotometer method. On the admission, and one, 3, 7 and 14 d after treatment, gastrointestina complications, pneumonias and prognoses of the two groups were compared. Results As compared with those in the nasogastric tube group, the serum levels of inflammatory related factors (TNF-α and IL-6) in the nasointestinal tube group were significantly decreased 3 d after treatment (TNF-α: [112.77± 14.52] μg/L vs. [163.16±18.85] μg/L P=0.01; IL-6: [80.11±8.02] μg/L vs. [100.97±9.82], P=0.02). As compared with those in the nasogastric tube group, the intestinal mucosal barrier function indexes (D-lactate acid and I-FABP) in the nasointestinal tube group were significantly decreased 7 d after treatment (D-lactate: [47.51±4.87] μg/L vs. [62.20±6.01] μg/L, P=0.04; I-FABP: [29.12±3.74] μg/L vs. [40.08±5.51] μg/L, P=0.01). The nasointestinal tube group had significantly lower gastric retention incidence (18% vs. 28%, P=0.00) and aspiration incidence (14% vs. 26%, P=0.06). Meanwhile, the nasointestinal tube group had significantly lower incidence of pneumonia (24% vs. 34%, P=0.01), reduced pneumonia severity (clinical pulmonary infection scores [CPIS]: 14.27±1.22 vs. 17.30±1.50, P=0.03), better prognosis (GCS scores: (9.41±0.66 vs. 8.23±0.57, P=0.03; APACHE II scores: 14.27± 1.22 vs. 17.30±1.50, P=0.03) 14 d after treatment as compared with the nasogastric tube group. Enteral nutrition by nasointestinal tube could shorten the hospitalization days of patients (18.52±2.00 vs. 24.82± 2.31, P=0.02). Conclusion Enteral nutrition by nasointestinal tube can effectively reduce the incidences of gastrointestinal and pulmonary complications, and alleviate inflammatory response and intestinal mucosal barrier function damage in patients with sTBI, possibly improving prognosis.
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Objective To investigate the effects of omega-3 polyunsaturated fatty acids (ω-3 PUFA) supplementation on neuron apoptosis,brain edema,activation of microglia,inflammatory response and neural function after traumatic brain injury (TBI) in rats,so as to understand the protection of ω-3 PUFA in rats following TBI and its mechanism.Methods TBI model was established using Feeney's method.Ninety SD rats were randomly divided into 5 groups:sham operation group (sham group),TBI group,TBI + selective activator of c-Jun N-terminal kinase (JNK) anisomycin group (TBI + Aniso group),TBI + ω-3 PUFA supplementation group (TBI + ω-3 group),and TBI + ω-3 PUFA supplementation + JNK activation group (TBI + ω-3 + Aniso group).We measured rat behavioral outcomes by modified neurological severity score (mNSS) on day 1,3,and 7 after TBI.Brain water content was measured with wet-dry weight method.The neuron apoptosis and microglial activation (identified by specific marker IBA-1) in TBI cerebral cortex were determined by TUNEL staining and immunofluorescence.Inflammatory cytokines [tumor necrosis factor-α (TNF-α),interleukin (IL)-1α,IL-1β,and IL-6] and the JNK signaling pathway (JNK,pJNK) were tested with reverse transcription-polymerase chain reaction and Western blot,respectively.Results Compared with the sham group,the levels of brain cell apoptosis,brain edema,neuron apoptosis,and inflammatory-relatived factors (TNF-α,IL-1 α,IL-1β,and IL-6) were significantly increased in the other four groups (P < 0.05).Compared with the TBl group,ω-3 PUFA supplementation reduced brain water content following TBI,especially on day 3 after TBI [(78.14 ± 0.57) % vs.(82.31 ± 0.81) %,P < 0.01],and improved neurological function score (P < 0.05).Meanwhile,ω-3 PUFA supplementation suppressed neuron apoptosis,the activation of microglia,and the mRNA and protein expressions of inflammatory cytokines (TNF-α,IL-1α,IL-1 β,IL-6).The activation of JNK signaling pathway was also inhibited by ω-3 PUFA.Conclusion ω-3 PUFA supplementation may markedly reduce brain edema,suppress neuron apoptosis,and improve neurological outcomes after TBI in rats,possibly mediated by inhibiting JNK signaling pathway and microglial activation,reducing microglia-induced cerebral inflammatory responses,demonstrated as down-regulated expression of TNF-α,IL-1α,IL-1β,and IL-6.
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Objective To investigate the effect of autophagy response on neurological functions and the role of mitogen-activated protein kinases (MAPKs) signaling pathway in rats after traumatic brain injury (TBI).Methods Fifty-four healthy male SD rats were randomly divided into sham-operated group,TBI group and TBI+autophagy inhibitor 3-methyladenine (3-MA) group (n=18).TBI animal models of the later two groups were established using Feeney's method.Rats in the sham-operated group were only performed bone window opening without knock;rats in the TBI+3-MA group were given intraperitoneal injection of 3-MA(5 mg/kg) 30 min after modeling and rats in the other two groups were given the same volume of normal saline.Three and 7 d after modeling,the protein levels of S100B and neuron specific enolase (NSE) in serum were tested with enzyme linked immunosorbent assay (ELISA);modified neurologic severity scale (mNSS) was used to detect the movement,sense and reflex functions;brain water content was measured with wet-dry weight method.The autophagy related factors (LC3-Ⅱ and Beclin-1) and MAPKs signaling pathway related factors (c-Jun N-terminal kinase [JNK],phosphorylated [p]-JNK,extracellular signal-regulated kinase [ERK]1/2,p-ERK1/2,p38MAPK and p-p38MAPK) protein expressions in TBI cerebral cortex were determined by Western blotting.Results As compared with those in the sham-operated group,the brain edema level,mNSS scores,and S100B and NSE protein levels in the TBI group and TBI+3-MA group were significantly increased (P<0.05);TBI+3-MA group had significantly lower brain edema level,mNSS scores,and S100B and NSE protein levels than TBI group (P<0.05).The expression levels of autophagy and MAPKs signaling pathway related factors in the TBI group and TBI+3-MA group were significantly higher as compared with those in the sham-operated group (P<0.05).As compared with the TBI group,TBI+3-MA group had significantly decreased levels of LC3-Ⅱ,Beclin-1 and activation of JNK and p-p38MAPK signaling pathways (P<0.05).Conclusion Suppressing autophagy response markedly improves neurological outcomes after TBI,possibly mediated by inhibiting activation of JNK and p38MAPK signaling pathways.
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Objective To investigate the prognostic significance of the angiolymphatic invasion(ALI) in patients with esophageal squamous cancer(ESCC) who received radical resection.Methods A retrospective review was performed on 355 patients who underwent radical resection for ESCC in our hospital between June 2005 and December 2008.Clinicopathological features and overall survival rate were surveyed.Results Of all the patients included, these 46 ESCC patients with angiolymphatic(ALI group) invasion accounted for 13.3%.The 5-year overall survival rate was 20.3% in patients of ALI group and 40.2% in those of non-ALI group(P =0.001).The histological differentiation was poorer in the ALI group (P =0.008) as compared with non-ALI group.Univariate analysis showed that body mass index(BMI), ALI, T stage, N stage, and differentiation were associated with survival(P < 0.05 for all).Multivariate analysis revealed that ALI, N stage, T stage and BMI were independent risk factors of prognosis.Conclusion This study highlights that ALI may facilitate the stratification of patients with a poor prognosis after radical resection for ESCC.
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Objective To investigate the effect of Jun N-terminal kinase (JNK) signaling pathway on inflammatory response,neuron apoptosis,brain edema,and neurobehavioral outcome after traumatic brain injury (TBI) in rats.Methods Fifty-four healthy male SD rats were randomly divided into 3 groups:sham-operated group,TBI group and JNK inhibitor group (n=18).Rats in the later two groups were established TBI animal models by using Feeney's method; rats in the sham-operated group were only opened the bone window without beating.Half h after TBI,intraperitoneal injection of SP600125 (15 mg/kg) was performed in rats of the JNK inhibitor group,while the same volume of solvent was given to rats in the other two groups.One,3 and 7 d after TBI,rat behavioral outcomes were measured by modified neurologic severity scale (mNSS),brain water content was measured with wet-dry weight method,and apoptosis neurons were detected by TUNEL.Three d after TBI,immunohistochemistry staining was used to determine the apoptosis relative proteins (caspase-3 and Bcl-2 associated X protein [Bax]) expressions in the cerebral cortex,real time PCR was employed to detect the mRNA expressions of inflammatory cytokines (tumor necrosis factor-α [TNFα],interleukin [IL]-1α,IL-1β,IL-6),and Western blotting was used to detect the protein expressions of TNFα,IL-1α,IL-1β,IL-6,JNK and phosphorylation-JNK (p-JNK).Results As compared with those in the sham-operated group,the mNSS scores,brain water content and apoptosis rate in TBI group and JNK inhibitor group were significantly higher 1,3 and 7 d after TBI (P<0.05); the mNSS scores in the JNK inhibitor group was statistically lower than those in the TBI group 3 and 7 d after TBI (P<0.05),and significantly reduced brain edema and improved neurobehavioral outcomes were noted in the JNK inhibitor group as compared with those in the TBI group 1,3 and 7 d after TBI (P<0.05).As compared with the TBI group,the JNK inhibitor group had significantly lower caspase-3 expression and increased Bcl-2 expression.As compared with those in the sham-operated group,the TNFα,IL-1α,IL-1β and IL-6 mRNA and protein expressions and p-JNK protein expression were significantly increased in the TBI group and JNK inhibitor group,and those in the JNK inhibitor group were statistically lower than those in the TBI group (P<0.05).Conclusion Suppressing activation of JNK signaling pathway can markedly improve the neurological outcomes after TBI,reduce brain edema and neuron apoptosis,which might be mediated by inhibiting TBI-induced cerebral inflammatory response and reducing the expression of TNFα,IL-1α,IL-1β and IL-6.
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Objective To explore the role of improved cranioplasty plus ventriculoperitoneal shunt in early treatment of hydrocephalus secondary to decompressive craniectomy for patients with severe craniocerebral injury. Methods A retrospective study was performed on 45 patients complicated by hydrocephalus after decompressive craniectomy for severe craniocerebral injury treated with early stage improved cranioplasty plus ventriculoperitoneal shunt from January 2006 to December 2010.Then,the clinical data,complications and outcomes were summarized. Results All operations were carried out 38-80 days after injury.The postoperative complications were distal obstruction of ventriculoperitoneal shunt in two patients and intracranial infection in one.The clinical symptoms were obviously improved in 36 patients (80%) and the cerebral ventricle was diminished in 34 (76%) one month postoperatively.The Glasgow Outcome Scale (GOS) at discharge was good in eight patients,moderate disability in 19,severe disability in 13 and prolonged coma in five,where better recovery (good recovery and moderate disability) in 27 patients (60%) showed significant improvement compared with preoperation ( x2 =23.47,P <0.01 ). Conclusion Early cranioplasty plus ventriculoperitoneal shunt is an effective and safe method for treatment of the complicated hydrocephalus after decompressive craniectomy for severe craniocerebral injury.
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Objective To investigate the clinical outcome of modified large decompressive craniectomy in treatment of severe traumatic brain injury combined with acute subdural hematoma. Methods A retrospective analysis was carried out to compare the clinical outcome of large decompressive craniectomy (treatment group) for 81 patients with severe traumatic brain injury combined with acute subdural hematoma from July 2007 to June 2010 and that of standard large trauma decompressive craniectomy (control group) for 65 patients with same injuries from July 2004 to June 2007. Results According to the Glasgow outcome scale at the end of month 6 after injury, there were 21 patients (GCS 5 points) with good recovery, 19 (GCS4 points) with moderate deficit, 24 (GCS 3 points) with severe deficit, five (GCS 2 points) under persistent vegetative status and 12 (GCS 1 points) deaths in the treatment group,with good prognosis rate (good recovery and moderate deficit) of 49% (P < 0.05) and poor prognosis rate of 51%. However, only 21 patients got favorable outcome, including 12 patients (GCS 5 points)with good recovery and nine (GCS 4 points) with moderate deficit; 44 patients got unfavorable outcome (68%), including 22 patients (GCS 3 points) with severe deficit, three (GCS 2 points) under persistent vegetative status and 19 (GCS 1 points) deaths in the control group (P <0.05). Furthermore, the incidences of delayed intracranial hematomas and subdural collection of fluid in the treatment group were significantly lower than those in the control group (P < 0.05). Conclusion Modified large decompressive craniectomy can significantly improve the outcome and reduce complications of patients with severe traumatic brain injury combined with acute subdural hematoma.