Xiaohang Wang

Infection of the central nervous system caused by enterovirus 71 (EV71) remains the main cause of death in hand‐foot‐and‐mouth disease. However, the mechanism responsible for how EV71 breaks through the blood‐brain barrier to infect brain cells has yet to be elucidated. By performing a high‐throughput small interfering RNA (siRNA) screening and validation, we found that the infection of human brain microvascular endothelial cells (HBMECs) by EV71 was independent of the endocytosis pathways mediated by caveolin, clathrin, and macropinocytosis but dependent on ADP‐ribosylation factor 6 (ARF6), a small guanosinetriphosphate (GTP)‐binding protein of the Ras superfamily. The specific siRNA targeting ARF6 markedly inhibited HBMECs susceptibility to EV71. EV71 infectivity was inhibited by NAV‐2729, a specific inhibitor of ARF6, in a dose‐dependent manner. The subcellular analysis demonstrated the co‐localization of the endocytosed EV71 and ARF6, while knockdown of ARF6 with siRNA remarkably influenced EV71 endocytosis. By immunoprecipitation assays, we found a direct interaction of ARF6 with EV71 viral protein. Furthermore, ARF1, another small GTP‐binding protein, was also found to participate in ARF6‐mediated EV71 endocytosis. Murine experiments demonstrated that NAV‐2729 significantly alleviated mortality caused by EV71 infection. Our study revealed a new pathway by which EV71 enters the HBMECs and provides new targets for drug development.

Aorto-esophageal fistula (AEF), a postoperative complication of esophagectomy, constitutes a very small percentage of all cases presenting with AEF; however, it is associated with a high mortality rate. Acute massive hemorrhage is the single largest cause of death in patients developing AEF. There is a lack of consensus on the optimal treatment of AEF. We present 3 cases secondary to esophagectomy due to lower thoracic esophageal carcinoma. All 3 patients presented with similar acute symptoms including a critical and life-threatening course with dead feeling, thoracic pain, and projectile hematemesis, and also hypovolemic shock. Digital subtraction angiography identified AEF as the diagnosis of these 3 cases. All patients were treated with emergency thoracic endovascular aortic repair, the aortic fistulas were repaired. All patients successfully survived the perioperative period. Thoracic endovascular aortic repair, a minimally invasive technique, is a better method to achieve faster and safer hemodynamic stability in patients with AEF compared with open thoracic aortic repair.

To investigate the expression of vascular endothelial growth factor-C (VEGF-C) and its relationship to lymph node metastasis in esophageal squamous cell cancer after esophagectomy. The expression of VEGF-C protein was detected by immunohistochemistry. Kaplan-Meier method was performed to calculate the survival rate. Cox regression multivariate analysis was performed to determine independent prognostic factors. The difference of VEGF-C protein expression in Tl, T2 and T3 patients was statistically significant (p=0.031). The expression of VEGF-C protein in patients with lymph node metastasis was significantly higher than those without metastasis (p=0.004). VEGF-C protein expression correlated with significantly worsened 5-year survival for all patients as well as those with T3 tumors and N1 nodal status. The result of Cox analysis demonstrated that N stage and VEGF-C protein expression were independent prognostic factors; the multivariate analyses indicated that the N classification is the independent pathological risk factor of VEGF-C expression. VEGF-C expression was found to be significantly associated with T stage and N stage. The patients with VEGF-C protein expression had a significantly lower 5-year survival rate than without VEGF-C protein expression. Lymph node metastasis and VEGF-C protein expression were independent prognostic factors.

Lung cancer invading left atrium or base of pulmonary vein belongs to locally advanced lung cancer (T4). The prognosis of treatment without surgery is poor. The aim of this study is to explore the feasibility and the value of surgical method in the treatment of this disease. From April, 1993 to April, 2005, lobectomy or pneumonectomy combined with extended resection of left atrium were carried out in 46 patients with locally advanced lung cancer. The operations included left low lobectomy in 20 cases, left pneumonectomy in 6 cases, right middle and low lobectomy in 12 cases, right low lobectomy in 3 cases and right pueumonectomy in 5 cases respectively. The base of the pulmonary vein was invaded by the tumor in 34 patients, while left atriums were invaded obviously in 12 patients. Two patients were operated using extracoporeal circulation because of main pulmonary artery and left atrium being invaded. The Kaplan-Meier method (Log rank test) and a COX model were used to analyse the survival and the prognosis. There was no operative mortality in this series, 15 patients had operative complication, including arrhythmia in 13 cases, pneumonia in 8 cases and heart failure in 1 case. The median survival was 35 months. The 1-, 3-, 5-year survival rates were 84.2%, 43.7%, 30.5% respectively. The survival of patients with N0/1 was better than that of patients with N2 disease, the median survival of them were 38 months and 19 months respectively (P=0.002). Using a Cox model analysis, lymph node stage (N0/1 or N2) was independent prognostic factor, while preoperative chemotherapy, sex, age and the pathologic type were not independent prognostic factors. Surgical treatment for lung cancer invading the left atrium or the base of pulmonary vein is feasible, especially for N0 patients.