Objective To investigate the effects and mechanisms of valproic acid on brain edema,neurobehavioral outcome and inflammatory response after traumatic brain injury (TBI) in rats.Methods TBI animal models were established using Feeney's method.Fifty-four SD male rats,weighting 220-250 g,were randomly divided into 3 groups (n =18):sham operation group (group sham),traumatic brain injury group (group TBI) and valproic acid treatment group (group TBI + VPA).Experimental rats were treated with valproic acid (300 mg/kg,twice daily) by intraperitoneal injection.Rat behavioral outcomes were measured by modified neurologic severity score (mNSS) tests at day 1,3,and 7 after TBI.Brain water content was measured with wet-dry weight method.The blood cells infiltration into cerebral cortex were tested with immunohistochemistry staining against ED-1 for macrophage.Inflammatory cytokines (INF-γ,tumor necrosis factor-α,interleukin-6) were measured by Western blotting.The statistical analysis were performed by ANOVA and chi-square tests using the statistical software program SPSS 13.0.Results Compared with the Sham group,the levels of brain edema,mNSS and macrophage cell infiltration were significantly increased after TBI (all P =0.00).The expressions of inflammatory cytokines were also increased significantly (all P =0.00).Compared with the TBI group,TBI + VAP group had significantly lower brain water content[3day:(80.12 ±0.59)％ vs.(82.14 ±0.67)％,P=0.04;7day:(74.74 ±0.72)％ vs.(77.93 ±0.48)％,P=0.01],and mNSS scores [3 day:(10.53 ±0.32) vs.(11.74 ±0.48),P =0.02;7 day:(7.97 ± 0.32) vs.(10.73 ± 0.42),P =0.01].VPA suppressed macrophage cell infiltration into cerebral cortex [(36.44 ± 0.72) ％ vs.(25.93 ± 0.48) ％ P =0.00].Meanwhile,VPA inhibited the expressions of inflammatory cytokines (INF-γ,TNF-α,IL-6) (P ＜ 0.05).Conclusions Treatment with VPA markedly reduced brain edema and improved neurological outcomes after TBI,possibly mediated by inhibited TBI-induced cerebral inflammatory responses and macrophage cell infiltrating into cerebral cortex.

OBJECTIVE To assess the association of copy number variations (CNVs) in chromosome 17q with the overall survival(OS) of patients with hepatocellular carcinoma(HCC), and to screen for target genes contained in the OS-related CNVs. METHODS A total of 174 HCC cases were enrolled. For 66 patients, the follow-up data was available. High-resolution Agilent Hu-244A array comparative genomic hybridization (aCGH) and Affymetrix U133 Plus 2.0 expression arrays were used to detect CNVs and gene expression of genes from the 17q region, respectively. The association of CNVs and OS was assessed with Log-rank test, Kaplan-Meier survival analysis, and Cox proportional hazards models. The gene expression in HCCs with 17q gain, HCCs without, and non-tumor liver tissues were compared with a Mann-Whitney U test. RESULTS Univariate association analysis showed that copy number gain in 17q25.1-25.3 was significantly associated with reduced OS (Log-rank test, P = 0.00002), and HCC cases with 17q25.1-25.3 gain had a 4.76-fold (95%CI: 2.31-9.81) increased hazard ratio (HR) for death from HCC, as compared to those without the gain. Multivariate Cox proportional hazards regression model revealed 17q25.1-25.3 gain to be an independent prognostic marker for poor OS (HR = 3.17, 95%CI: 1.39-7.26, P = 0.006). The expression levels of 18 genes in 17q25.1-25.3 including SLC9A3R1, GRB2, and TK1 were significantly increased in HCCs with gain than in those without (all P < 0.01) and non-tumor liver tissues (all P < 0.01). CONCLUSION The association of 17q25.1-25.3 gain with reduced OS has indicated that it is a prognostic marker for poor patient survival in HCC, for which SLC9A3R1, GRB2, and TK1 are candidate genes.
Adult ; Aged ; Carcinoma, Hepatocellular ; genetics ; mortality ; Chromosomes, Human, Pair 17 ; DNA Copy Number Variations ; Female ; Humans ; Liver Neoplasms ; genetics ; mortality ; Male ; Middle Aged

Objective To investigate the clinical efficacy of basiliximab-induced glucose-free corticosteroid immunosuppressive regimen after liver transplantation.Methods The retrospective cohort study was conducted.The clinicopathological data of 227 patients with liver transplantation who were admitted to Bayi Hospital affiliated to Nanjing University of Traditional Chinese Medicine from January 2010 to October 2016 were collected.Of the 227 patients,125 who postoperatively received a glucose-free corticosteroid immunosuppressive regimen using a monoclonal antibody + tacrolimus + mycophenolate mofetil tablets were allocated into the hormone-free group,and 102 who were postoperatively treated with the immunosuppressive regimen using glucocorticoid steroid + tacrolimus + mycophenolate mofetil tablets were allocated into the hormone group.Observation indicators:(1) comparison of follow-up and survival;(2) comparison of postoperative infection,rejection and biliary stenosis between groups.Follow-up using outpatient examination and telephone interview was performed to detect postoperative survival,infection,rejection and biliary stenosis up to June 2017.The measurement data with normal distribution were represented as (x) ± s,and comparison between groups was done by the t test.Measurement data with skewed distribution were described as M (P25,P75) and M (range),and comparison between groups was analyzed using the rank sum test.The count data were compared by the chi-square test.Kaplan-meier method was used to draw survival curve and calculated survival rate.Log-rank test was used for survival analysis.Results (1) Comparison of follow-up and survival:patients between groups were followed up for 9-89 months,with a median time of 45 months.The 1-and 3-year overall survival rates were respectively 93.25％,85.24％ in the hormone-free group and 89.89 ％,74.22％ in the hormone group,with a statistically significant difference (x2 =8.450,P＜0.05).(2) Comparison of postoperative infection,rejection and biliary stenosis between groups:① The total cases with postoperative infections,cases with infection of Klebsiella pneumoniae,Staphylococcus aureus,Candida,Acinetobacter baumannii and Stenotrophomonas maltophilia were 25,18,3,2,2,0 in the hormone-free group and 40,26,6,3,3,2 in the hormone group,respectively,showing a statistically significant difference between groups (x2 =10.149,P＜0.05).The patients between groups with postoperative infection were treated with active anti-infective symptomatic treatment.Three patients in the hormone group died of severe pulmonary infection,and the remaining patients in both groups were improved.② The cases with postoperative rejection in the hormone-free group and hormone group were 6 and 5,respectively,with no statistically significant difference (x2 =0.950,P＞ 0.05).The rejection of both groups occurred within 1 week postoperatively.Two patients in the hormone group were treated with glucocorticoid hormonal shock.The other patients in the 2 groups were improved by adjusting the amount of tacrolimus and mycophenolate mofetil tablets.③ The cases with postoperative biliary stenosis in the hormone-free group and the hormone group were 32 and 8 respectively,with a statistically significant difference (x2 =12.200,P＜0.05).In the hormone group,biliary stenosis occurred after stopping glucocorticoids.The patients with biliary stenosis were improved after biliary stent implantation by endoscopic retrograde cholangio pancreatography (ERCP).Conclusion The basiliximab-induced glucose-free corticosteroid immunosuppressive regimen after liver transplantation is safe and feasible,and it can significantly reduce the incidence of postoperative infection and improve long-term overall survival compared with the conventional glucocorticoid immunosuppressive regimen,but increased postoperative biliary stenesis.

Objective: To investigate the molecular markers of copy number aberrations (CNAs) of genes related to extrohepatic metastasis-free survival after the operation for hepatocellular carcinoma (HCC). Methods: The CNA status of 20 candidate genes in 66 HCC samples was detected by microarray comparative genomic hybridization. The associations between gene CNAs and extrohepatic metastasis-free survival were evaluated using the Cox regression model, Log-rank test, and Kaplan-Meier survival analysis. Results: Multivariate Cox analysis revealed that the independent risk factors for metastasis-free survival were MDM4 gain (hazard ratio [HR] = 2.74, 95% confidence interval [CI] = 1.18-6.37, P < 0.05), APC loss (HR = 8.43, 95% CI = 2.48-28.66, P < 0.01), and BCL2L1 gain (HR = 3.45, 95% CI = 1.13-10.52, P < 0.05) and the independent protective factor was FBXW7 loss (HR = 0.32, 95% CI = 0.12-0.89, P < 0.05). By stepwise Cox regression analysis, three CNAs related to metastasis-free survival were screened out: MDM4 gain (HR = 2.71, 95% CI = 1.11-6.64, P < 0.05), APC loss (HR = 7.19, 95% CI = 1.88-27.60, P < 0.005), and FBXW7 loss (HR = 0.16, 95% CI = 0.05-0.46, P < 0.01). There were significant differences in metastasis-free survival rate between the HCC patients with FBXW7 loss and without MDM4 gain or APC loss, those with MDM4 gain and/or APC loss and without FBXW7 loss, and those with other CNA combinations (log-rank test, P < 0.01). Conclusion MDM4 gain, APC loss, and FBXW7 loss are the independent prognostic factors for extrohepatic metastasis-free survival after the operation for HCC and can be used to predict the risk of extrohepatic metastasis after the operation for HCC.