BACKGROUND: Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI. METHODS: In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining and transmission electron microscopy. RESULTS: A low dose of ATO (0.75 μmol/L in vitro and 1 mg/kg in vivo ) significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitro  studies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent. CONCLUSION Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.
Animals ; Arsenic Trioxide ; Autophagy/physiology* ; Reperfusion Injury/prevention & control* ; Mice ; Male ; Proto-Oncogene Proteins c-akt/physiology* ; Arsenicals/therapeutic use* ; Oxides/therapeutic use* ; Liver/metabolism* ; Extracellular Signal-Regulated MAP Kinases/metabolism* ; Mice, Inbred C57BL

Objective: To evaluate the significance of different clinicopathologic features on prognosis of patients with squamous cell carcinoma of vulva. Methods: We retrospectively analyzed the prognostic relevance of different clinicopathological variables of 201 patients with squamous cell carcinoma of vulva treated in Cancer Hospital, Chinese Academy of Medical Sciences. The data including age, initial symptoms, stage, location, tumor size, histological grade, number and size of metastatic lymph nodes, treatment mode, and presence of leukoplakia vulva was used to evaluate the prognosis of vulvar squamous cell carcinoma. Results: The median age of onset was 62.0 years old, with 74 patients in stage Ⅰ, 27 in stage Ⅱ, 55 in stage Ⅲ and 9 in stage Ⅳ. The median progression-free survival was 90.0 months. The 5-year progression-free survival rate of the total patients was 55.5%, while the 10-year progression-free survival rate was 48.5%. Univariate analysis showed statistically significant prognostic parameters included clinical stage, number of metastatic lymph nodes, tumor size and treatment mode (all P<0.001). Multivariate analysis showed that number of metastatic lymph nodes (P<0.05) was an independent prognostic factor for progression-free survival. Conclusion The study illustrates that number of metastatic lymph nodes represents important independent factor for progression-free survival of patients with vulvar squamous cell carcinoma.

Objective To evaluate the significance of different clinicopathologic features on prognosis of patients with squamous cell carcinoma of vulva. Methods We retrospectively analyzed the prognostic relevance of different clinicopathological variables of 201 patients with squamous cell carcinoma of vulva treated in Cancer Hospital, Chinese Academy of Medical Sciences. The data including age, initial symptoms, stage, location, tumor size, histological grade, number and size of metastatic lymph nodes, treatment mode, and presence of leukoplakia vulva was used to evaluate the prognosis of vulvar squamous cell carcinoma. Results The median age of onset was 62.0 years old, with 74 patients in stage Ⅰ, 27 in stage Ⅱ, 55 in stage Ⅲ and 9 in stage Ⅳ. The median progression?free survival was 90.0 months. The 5?year progression?free survival rate of the total patients was 55.5%, while the 10?year progression?free survival rate was 48.5%. Univariate analysis showed statistically significant prognostic parameters included clinical stage, number of metastatic lymph nodes, tumor size and treatment mode ( all P＜0.001 ). Multivariate analysis showed that number of metastatic lymph nodes ( P＜0.05 ) was an independent prognostic factor for progression?free survival. Conclusion The study illustrates that number of metastatic lymph nodes represents important independent factor for progression?free survival of patients with vulvar squamous cell carcinoma.

Objective To evaluate the significance of different clinicopathologic features on prognosis of patients with squamous cell carcinoma of vulva. Methods We retrospectively analyzed the prognostic relevance of different clinicopathological variables of 201 patients with squamous cell carcinoma of vulva treated in Cancer Hospital, Chinese Academy of Medical Sciences. The data including age, initial symptoms, stage, location, tumor size, histological grade, number and size of metastatic lymph nodes, treatment mode, and presence of leukoplakia vulva was used to evaluate the prognosis of vulvar squamous cell carcinoma. Results The median age of onset was 62.0 years old, with 74 patients in stage Ⅰ, 27 in stage Ⅱ, 55 in stage Ⅲ and 9 in stage Ⅳ. The median progression?free survival was 90.0 months. The 5?year progression?free survival rate of the total patients was 55.5%, while the 10?year progression?free survival rate was 48.5%. Univariate analysis showed statistically significant prognostic parameters included clinical stage, number of metastatic lymph nodes, tumor size and treatment mode ( all P＜0.001 ). Multivariate analysis showed that number of metastatic lymph nodes ( P＜0.05 ) was an independent prognostic factor for progression?free survival. Conclusion The study illustrates that number of metastatic lymph nodes represents important independent factor for progression?free survival of patients with vulvar squamous cell carcinoma.

Objective To investigate the prognosis of patients with solitary large hepatocellular carcinoma (SLHCC) and with small hepatocellular carcinoma (SHCC),and analyze the risk factors affecting the prognosis of patients with SLHCC.Methods The retrospective case-control study was conducted.The clinicopathological data of 856 patients with hepatitis B virus (HBV)-related HCC who were admitted to the Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University from January 2008 to December 2008 were collected.Of 856 patients,693 HCC patients with tumor diameter ≤5 cm were allocated into the SHCC group and 163 HCC patients with tumor diameter ＞ 5 cm and with solitary,expansive growth and complete capsule tumors were allocated into the SLHCC group.Patients underwent preoperative antiviral therapy,laboratory and imaging examinations,and then surgical planning was determined based on the preoperative results.Observation indicators:(1) comparisons of clinicopathological features between the 2 groups:sex,age,Child-Pugh grade,HBeAg,serum level of HBV-DNA,platelet (PLT),albumin (Alb),total bilirubin (TBil),alpha-fetoprotein (AFP),tumor diameter,microvascular invasion,Edmondson-Steiner grade and liver cirrhosis;(2) treatment situations between the 2 groups:surgical procedures,operation time,volume of intraoperative blood loss,number of patients with blood transfusion and time of hepatic inflow occlusion;(3) survival analysis between the 2 groups;(4) prognostic analysis of patients with SLHCC.Follow-up using telephone interview and outpatient examination was performed once every 3 months within 2 years postoperatively and once every 6 months after 2 years postoperatively up to June 23,2014.Follow-up included tumor marker,liver function,serum level of HBV-DNA and abdominal B-ultrasound examination.The patients received reexamination of computed tomography (CT) or magnetic resonance imaging (MRI) once every 6 months or when there was suspicion of tumor recurrence or metastasis.Tumor recurrence or metastasis was confirmed through typical HCC imaging findings of CT and MRI,and PET/CT examination was conducted if necessary.Tumor-free survival time was from operation time to time of tumor recurrence,and overall survival time was from operation time to death or the last follow-up.Measurement data with normal distribution were represented as-x±s,and continuous variables were analyzed by the t test or Mann-Whitney U test.Measurement data with skewed distribution were described as M (range).Categorical variables were represented as count (percentage) and analyzed by the chi-square test or calibration chi-square test.The survival curve and survival rate were respectively drawn and calculated by the Kaplan-Meier method and Log-rank test.COX regression model was used for prognostic analysis.Results (1) Comparisons of clinicopathological features between the 2 groups:number of patients with PLT＜ 100× 109/L,with positive microvascular invasion and with liver cirrhosis and tumor diameter were 197,133,447,(3.1±1.1)cm in the SHCC group and 28,53,79,(8.9±3.3) cm in the SLHCC group,respectively,with significant differences between the 2 groups (x2=28.618,t =37.286,x2 =213.773,214.325,P ＜ 0.05).(2) Treatment situations between the 2 groups:all the 856 patients underwent hepatectomy,including 326 with hepatic segments of resection ≥ 3 and 530 with hepatic segments of resection ＜ 3.Operation time,volume of intraoperative blood loss,number of patients with intraoperative blood transfusion and with time of hepatic inflow occlusion ＞ 20 minutes were 90 minutes (range,60-200 minutes),200 mL (range,20-5 200 mL),47,125 in the SHCC group and 110 minutes (range,60-230 min),300 mL (range,50-3 200 mL),31,58 in the SLHCC group,respectively.(3) Survival analysis between the 2 groups:all the 856 patients were followed up for 32.5 months (range,1.O-72.3 months).The median survival time,median tumor-free survival time,1-,3-,5-year overall survival rates and 1-,3-,5-year tumor-free survival rates were 56.2 months (range,1.6-75.8 months),39.5 months(range,1.0-75.0 months),90％,71％,58％,70％,48％,38％ in the SHCC and 50.3 months (range,1.1-76.0 months),30.7 months (range,1.0-72.0 months),87％,59％,47％,65％,46％,33％ in the SLHCC group,respectively,with no significant difference in tumor-free survival between the 2 groups (x2=0.514,P＞0.05) and with a significant difference in overall survival between the 2 groups (x2=10.067,P＜0.05).Stratified analysis:there were 117 SLHCC patients with 5 cm ＜ tumor diameter ＜ 10 cm and 46 SLHCC patients with tumor diameter ＞ 10 cm.The 1-,3-,5-year overall survival rates and 1-,3-,5-year tumor-free survival rates were 91％,65％,53％,70％,48％,35％ in 117 SLHCC patients with 5 cm ＜ tumor diameter ＜ 10 cm,respectively,with no significant difference compared with SHCC group (x2=1.832,0.042,P＞0.05).The 1-,3-,5-year overall survival rates and 1-,3-,5-year tumor-free survival rates were 78％,46％,31％,49％,39％,30％ in 46 SLHCC patients with tumor diameter ＞ 10 cm,respectively,with significant differences compared with SHCC group (x2=21.136,4.097,P＜0.05).(4) Prognostic analysis of patients with SLHCC:results of univariate analysis showed that serum level of HBV-DNA,tumor diameter and microvascular invasion were risk factors affecting postoperative 5-year tumor-free survival rate of SLHCC patients (x2 =5.193,3.377,5.509,P＜0.05);sex,serum level of HBV-DNA,tumor diameter and microvascular invasion were risk factors affecting postoperative 5-year overall survival rate of SLHCC patients (x2=4.546,18.053,7.780,10.569,P＜0.05).Results of multivariate analysis showed that serum level of HBV-DNA ≥ 104 U/mL,tumor diameter ＞ 10 cm and positive microvascular invasion were independent risk factors affecting postoperative 5-year tumor-free survival rate of SLHCC patients [HR =2.77,1.85,1.86,95％ confidence interval (CI):1.74-4.40,1.16-2.94,1.17-2.96,P＜ 0.05] and affecting postoperative 5-year overall survival rate of SLHCC patients (HR=2.73,1.98,1.69,95％CI:1.72-4.33,1.23-3.17,1.04-2.72,P＜0.05).Conclusions There are similar prognosis between SLHCC patients with 5 cm ＜ tumor diameter ＜ 10 cm and SHCC patients,however,prognosis of SLHCC patients with tumor diameter ＞ 10 cm is worse than that of SHCC patients.Serum level of HBV-DNA ≥ 104 U/mL,tumor diameter ＞ 10 cm and positive microvascular invasion are independent risk factors affecting prognosis of SLHCC patients.

Objective To investigate the nuclear factor-erythroid 2-related factor (Nrf-2),and heme oxidase 1 (HO-1) expression in acute lung injury induced by paraquat poisoning in rats and explore the mechanism of lipoic acid acting on protection of lung from paraquat poisoning.Methods Seventy-two adult healthy male Sprague Dawley (SD) rats were randomly divided into three groups with different treatments designated as:control group (control group,n =12),paraquat group (PQ group,n =30) and paraquat + lipoic acid group (LA group,n =30).PQ group and LA group were randomly divided into five subgroups (n =6 in each) according to 6 h,12 h,24 h,48 h and 72 h after modeling and treatment.The rats in PQ group and PQ + LA group were treated with intra-peritoneal injection (ip) of PQ (25 mg/kg),while the rats in control group were treated with the equal volume of saline instead.Half an hours after intra-peritoneal injection of PQ,lipoic acid (100 mg/kg) was injected into caudal vein of rats once a day until they were sacrificed.The body weight was measured everyday.The rats of each group were sacrificed at the given intervals,and lung tissues were harvested to measure lung coefficient of rats.The same part of left lung of rats in each group was taken for HE staining and immunohistochemistry in order to detect the expressions of Nrf2 and HO-1.The right lung of rats in each group was taken for the detection of GSH-Px and SOD activity.All data were analyzed by using the One-way analysis of variance (ANOVA) and SNK-q test.Results The body weight reduction in LA group (191.02 ± 0.82) g,(183.37 ± 7.74) g was significantly less than that in PQ group (183.85 ± 2.07) g,(173.13 ± 4.34) g at 48 h and 72 h after PQ poisoning,respectively (P ＜ 0.01,P ＜ 0.05).The lung coefficient in LA group (6.83 ± 0.48) mg/g,(7.61 ±0.28) mg/g,(8.29 ±0.36) mg/g was less compared with PQ group (7.39 ±0.53) mg/g,(8.48±0.23) mg/g,(9.06±0.10) mg/g at 24 h,48 h,and 72 h,respectively (P＜0.01,P＜ 0.05).The immunohistochemical expressions of Nrf-2 in LA group (3.99 ±0.50),(3.51 ±0.12) were higher than those in PQ group (1.33 ±0.22),(1.62 ±0.41) at 48 h and 72 h.The immunohistochemical expression of HO-1 in LA group (1.76 ±0.17) was higher than that in PQ group (1.31 ±0.15) at 72 h.The levels of GSH-Px activity in LA group were significantly higher in comparison with PQ group at 24h,48h,and 72h (P ＜0.01,P ＜0.05).The levels of SOD activity in the LA group were significantly higher in comparison with PQ group at 6 h,12 h,24 h,48 h,and 72 h after PQ administration (P ＜ 0.01).Conclusions Nrf2-ARE (antioxidant response element) signaling pathway is involved in the pathogenesis of acute lung injury induced by paraquat poisoning,and lipoic acid may protect acute lung injury in rats induced by paraquat poisoning through Nrf2-ARE signaling pathway.

Objective: To investigate the impact factors for central neck lymph node metastases(CLNM) of papillary thyroid carcinoma(PTC). Methods: A total of 498 patients with PTC who underwent total or hemi-thyroidectomy plus central neck lymph node dissection between January 2014 and July 2016 were included. Univariate and multivariate analyses were performed to identify clinicopathological characteristics, thyroid function parameters and US findings that associated with CLNM of PTC. A nomogram was developed to predict the probability of CLNM. The receiver operating characteristic curve(ROC) was used to estimate the efficiency of the nomogram. Results: Among 498 patients, 284 patients were affected by CNLM. The sensitivity and specificity of US in predicting PTC metastasis in the central neck were 31.3% and 88.3%, respectively. Univariate and multivariate analyses showed that gender, age, number and size of suspicious malignant nodules in thyroid, and suspicious lymph node metastasis detected by ultrasonography were independently correlated with CLNM. The ROC showed that the AUC was 0.748, with sensitivity of 80.8%, and specificity of 59.8%. Conclusions Gender, age, number and size of suspicious malignant nodules in thyroid, suspicious lymph node metastasis were predictive factors for CLNM in patients with PTC. The nomogram developed based on related factors with CLNM is more sensitive than sonographic central neck lymph node features in predicting the probability of CLNM.

Objective The incidence of breast cancer in China obviously keeps rising in recent years. The optical tomo?graphy image ultrasonography system ( OPTIMUS) is gradually applied in clinic as a new imaging diagnostic technique, but few system?atic studies are reported on its application to the diagnosis of breast tumors. The aim of this study was to assess the value of OPTIMUS in differentiating benign and malignant breast masses by measuring the maximum hemoglobin concentration ( MHC) in the lesions using OPTIMUS with the help of the results of controlled pathological study. Methods This prospective study included 380 cases of breast tumor ( 210 benign and 170 malignant ) treated from April 2009 to April 2014. We measured the MHC using OPTIMUS, detected the expressions of VEGF and PECAM?1/CD31 by immunohistochemistry, calculated the optimal threshold valve of MHC in predicting breast malignancy with the ROC curve, and analyzed the correlation of the MHC value with benign and malignant lesions, lymph node metasta?sis, and the expressions of VEGF and PECAM?1/CD31. Results The mean MHC was significantly higher in the malignant than in the benign lesions ([215.33±69.31] vs [116.50±55.31] μmol/L, P<0.01). The area under the ROC curve (AUC) was 0.836 (95%CI 0.684-0.989). The optimal threshold valve in the diagnosis of malignant breast lesions was 135.00 μmol/L, with a sensitivity of 84.7% and a specificity of 89%. When the tumor was≤2 cm, the MHC was significantly higher in the patients with lymph node metas?tasis than in those without ([207.73±66.43] vs [184.36±62.13] μmol/L, P<0.05). However, the MHC was markedly lower in the benign masses with VEGF and PECAM?1/CD31 negative than in the malignant lesions with VEGF and PECAM?1/CD31 positive ([116.50±55.31] vs [205.73±72.46] μmol/L, P<0.05) and strongly positive ([244.21±63.56] μmol/L, P<0.05). Strongly posi?tive expressions of VEGF and PECAM?1/CD31 were positively correlated with MHC ( P<0.05) . Conclusion Measurement of MHC by OPTIMUS contributes to the differential diagnosis of benign and malignant breast lesions and has a potential value for preoperative assessment of the prognosis of breast cancer.

Objective To analyze the characteristics of multilayer spiral CT (MSCT) in chronic pyelonephritis,and to explore its clinical value in the diagnosis of chronic pyelonephritis.Methods 30 patients with chronic pyelonephritis were examined by MSCT enhancement scan,intravenous pyelogram (IVP) and double kidney color dopplar ultrasound.25 healthy people were selected as the control group.Two different seniority doctors evaluated the results separately.Results The diagnosis of two physicians had high consistency(K=0.8 1,P ＜ 0.05).In addition,compared with IVP and color dopplar ultrasound,the diagnostic rate of MSCT enhancement scanning in the renal parenchyma sag sign,renal pelvis wall thickening,strengthen and calyces mild deformation were significantly higher (P ＜ 0.05).Conclusion MSCT can clearly observe kidney form change in patients with chronic pyelonephritis,diagnostic rate is higher,it is worth clinical promotion.

Objective To analyze the clinical characteristics,diagnoses,treatments and prognoses of vaginal leiomyosarcoma (LMS).Methods The clinical and pathological recordings of 9 patients suffering from vaginal leiomyosarcoma from January 1973 to May 2011 were analyzed retrospectively.Results The study group constituted 2.7％ (9/330) of all the malignant vaginal tumor admitted to our hospital in the same period.The major clinical manifestations were asymptomatic vaginal mass (3/9),bellyache and vaginal bleeding (2/9),vaginal pain (2/9),and difficulty in defecation (1/9) and micturition (1/9).Preoperative diagnosis was highly unreliable.Based on the sample chose,the diagnosis were made in 3 cases by preliminary biopsy before undertaking surgery,while 6 cases were confirmed shortly after simple tumor excision or unexpected recurrence.All the patients were pathologically confirmed diagnosis by tumor resection specimen or biopsy,5 cases of them were also confirmed by virtue of immunohistochemistry staining.All 9 patients,8 cases received initial surgery,four of them patients received postoperative adjuvant chemotherapy or radiation therapy,the remaining 1 patients received initial chemotherapy and radiotherapy.Follow-up was performed for all the 9 patients,of which 3 cases were lost,the median follow-up time was 50 months (range 7-134).Four patients underwent local recurrence and adjacent organ metastases within two years,with 5 years survival rate 4/9.Conclusions Primary vaginal leiomyosarcoma is a rare and difficult to diagnose preoperatively tumor.In this regard,It is strongly recommend preoperative biopsy for definitive diagnosis and perform surgery as the principal approach,in conjunction with radiotherapy or chemotherapy when needed to improve survival.