Background Preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) may optimize individualized treatment decision-making. This study aimed to investigate the prognostic differences between HCC patients undergoing liver resection (LR) and liver transplantation (LT) based on predicted MVI risks. Methods We analysed 905 patients who underwent LR, including 524 who underwent anatomical resection (AR) and 117 who underwent LT for HCC within the Milan criteria using propensity score matching. A nomogram model was used to predict preoperative MVI risk. Results The concordance indices of the nomogram for predicting MVI were 0.809 and 0.838 in patients undergoing LR and LT, respectively. Based on an optimal cut-off value of 200 points, the nomogram defined patients as high- or low-risk MVI groups. LT resulted in a lower 5-year recurrence rate and higher 5-year overall survival (OS) rate than LR among the high-risk patients (23.6% vs 73.2%, P < 0.001; 87.8% vs 48.1%, P < 0.001) and low-risk patients (19.0% vs 45.7%, P < 0.001; 86.5% vs 70.0%, P = 0.002). The hazard ratios (HRs) of LT vs LR for recurrence and OS were 0.18 (95% confidence interval [CI], 0.09-0.37) and 0.12 (95% CI, 0.04-0.37) among the high-risk patients and 0.37 (95% CI, 0.21-0.66) and 0.36 (95% CI, 0.17-0.78) among the low-risk patients. LT also provided a lower 5-year recurrence rate and higher 5-year OS rate than AR among the high-risk patients (24.8% vs 63.5%, P = 0.001; 86.7% vs 65.7%, P = 0.004), with HRs of LT vs AR for recurrence and OS being 0.24 (95% CI, 0.11-0.53) and 0.17 (95% CI, 0.06-0.52), respectively. The 5-year recurrence and OS rates between patients undergoing LT and AR were not significantly different in the low-risk patients (19.4% vs 28.3%, P = 0.129; 85.7% vs 77.8%, P = 0.161). Conclusions LT was superior to LR for patients with HCC within the Milan criteria with a predicted high or low risk of MVI. No significant differences in prognosis were found between LT and AR in patients with a low risk of MVI.

Acrylamide (ACR) is a potential neurotoxin commonly found in the environment, as well as in food repeatedly exposed heat processing, but the mechanism underpinning ACR-induced neurotoxicity remains unclear. This study investigated the potential association and underlying signal transduction of oxidative stress, apoptosis, and autophagy associated with ACR-triggered neurotoxicity. Therefore, U87-MG cells were treated with varying ACR concentrations, while the cell activity reduction depended on the specific dosage and time parameters. Biochemical analyses showed that ACR significantly increased the reactive oxygen species (ROS), malondialdehyde (MDA), and Ca2+ levels while decreasing the glutathione (GSH) levels and mitochondrial membrane potential (ΔΨm), finally leading to a higher cell apoptotic rate. Moreover, ACR induced U87-MG cell apoptosis and autophagy via ROS-triggered expression in the mitochondrial apoptosis pathway, NF-κB activation, and autophagosome accumulation. In addition, the autophagosome accumulation induced by ACR could probably be ascribed to blocked autophagic flux, inhibiting the autophagosomes from combining with lysosomes, while the inhibition of autophagy caused by ACR further promoted the initiation of apoptosis. In conclusion, the results indicated that the apoptotic and autophagic pathways responded to ACR-induced neurotoxicity. However, inhibited protective autophagy further promoted apoptotic progression. New insights may be derived from these cellular responses that can help develop diverse pathway strategies for assessing the risk posed by ACR.HIGHLIGHTSACR induced mitochondrial- and caspase-dependent apoptosis in U87-MG cells.ACR regulated the autophagic markers and blocked autophagic flux in U87-MG cells.ACR inhibited protective autophagy and promoted apoptotic initiation in U87-MG cells.

Although more and more clinical studies indicated that ImmuKnow assay could efficiently assess the immune status of recipients, it still has the challenge to predict the occurrence of clinical adverse events. This study aimed to establish a quantitative assessment model, which could more efficiently predict immune function of T lymphocytes after liver transplantation based on three indexes: CD4+ T lymphocyte count (C), CD4+/CD8+ ratio (R), and ImmuKnow adenosine triphosphate (ATP) value (A). We selected 194 recipients and measured the A, C, and R index every week, then obtained the Fisher linear discriminant functions by SPSS 16.0. Next, we divided the recipients into three groups: infection, stable, and rejection groups according to clinical status. After calculating, the discriminant function, 0.012A+0.019C+1.322R (simplified into T=2A+3C+200R), was selected to represent the T-cell-mediated immune function. Based on the model, the optimal cutoff T values for infection and rejection were 1415 (sensitivity=80%, specificity=79.9%,AUC=92.3%) and 1939.5 (sensitivity=93.9%, specificity=77.6%, AUC=88.6%), relatively (p<0.001). In conclusion, this model may be a more feasible way to evaluate the cellular immune function status in liver transplantation recipients.

Objective To explore the monitoring and the individualized adjustment of cellular immunology function in the recipients infected with pan-drug resistant Acinetobacter baumannii(PDR-Ab)after liver transplantation.Methods We retrospectively summarized the infection and the prognosis of PDR-Ab in 299 cases of liver transplantation performed from Jan.2008 to May 2010.The absolute number of T lymphocytes and ATP level within CD4+ T cells were monitored,and T cell immunology function(TCIFS)was scored.According to different immunology adjusting proposals,14 cases of PDR-Ab infection were divided into 2 groups:(1)traditional group,routine anti-infective therapy;(2)individualized group.Individualized immunology adjustment was made according to the score of TCIFS besides routine therapy.Results There was no significant difference in age,MELD and Child-pugh score between two groups.The peri-operative bleeding volume in individualized group was more than that in traditional group(P<0.01).There was no significant difference in TCIFS score between two groups at 1st week after transplantation and the onset of the PDR-Ab infection.However,the score in individualized group was apparently higher than that in traditional group when anti-infection therapy ended(P<0.05).The difference in the recovery rate between two groups was significant(P<0.05).No rejection happened in two groups.Conclusion It is an effective way to decrease the mortality of PDR-Ab infection after liver transplantation that the individualized adjustment of immunosuppression protocols is guided by grading quantitatively the cellular immunology function according to the absolute number of T lymphocytes and ATP level within CD4+ T cells.

目的 探讨CD4+T细胞的ATP含量与肝移植术后早期(术后1个月内)感染的相关性.方法 采集85例肝移植患者、60名健康志愿者(对照组)的全血标本,术前、术后1、2、4周及感染当日和经治疗后体温正常3 d各1份;用ImmuKnowTM免疫细胞功能测定试剂盒检测CD4+T细胞的ATP值.结果 感染组ATP值在术前较低,术后第1周达到低谷,显著低于同期非感染组(P<0.01).经ROC曲线分析,术后第1周的低ATP值对诊断肝移植术后感染具有较好的敏感度和特异度;当截断值为161 μg/L时,其诊断感染的敏感度为85%,特异度为91%.感染当日的ATP含量降低与感染具有良好的相关性,经抗感染治疗体温正常3 d后,其ATP值较感染当日明显升高(P<0.01).结论 肝移植术后早期CD4+T细胞的ATP值动态变化与肝移植术后感染具有良好的相关性,监测肝移植术后患者该指标对评估其免疫状态、预防和诊治感染具有一定价值.

Objective To explore the relationship between ATP content in CD4+ T lymphocytes and acute rejection after liver transplantation(LT). Methods This study contained 77 patients who received LT from February to October 2009, They were divided into AR (acute rejection) and NAR (non-acute rejection) groups while 56 healthy people were enrolled to serve as the control group.Blood specimens were collected preoperatively and at 1, 2 and 4 weeks postoperatively. For the AR group, specimens were also collected on the day when AR occurred and 1 week after steroid bump together with that of the healthy people. ImmuKnowTM test kits for immune cell function were used to assay the ATP value. Results ATP values within CD4+T lymphocytes were elevated significantly in each group compared with those preoperatively. Peak level was reached in the AR group and was significantly higher than that of the contemporary NAR group (P＜0.05). ROC curve analysis showed that the obvious elevation of the ATP value within CD4+ T lymphocytes 1 week postoperatively had better sensitivity and specificity in diagnosing AR. The ATP sensitivity rate for early AR was 84.6 %and specificity rate 81 %. The ATP value within CD4+ T lymphocytes on the day of AR occurrence had a positive relationship with the rejection acting index(RAI), while relative index (r) was 0. 876(P＜0.05). After the steroid dump treatment, AR in all the patients was reversed and the ATP value declined significantly as compared with the control group and the day when AR occurred(P＜0. 05).Conclusion During the postoperative period, the dynamic change of ATP value within CD4 + T lymphocyte had a close relationship with acute rejection after liver transplantation. Thus, it might be used as a feasible and noninvasive monitoring index for diagnosing AR and the effectiveness of the anti-rejection treatment.