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.

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.

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.

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.

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.

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.

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.