Objective: Nonalcoholic fatty liver disease (NAFLD) has become a common chronic liver disease that is harmful to human health. Moreover, there is currently no FDA-approved first-line drug for the treatment of nonalcoholic steatohepatitis (NASH) or NAFLD. Traditional Chinese medicine (TCM) is widely used to ameliorate liver diseases, such as the traditional ancient recipe called Three Flower Tea (TFT), which consists of double rose (Rosa rugosa), white chrysanthemum (Chrysanthemum morifolium), and Daidaihua (Citrus aurantium). However, the mechanisms of the action of TFT are not clear. Therefore, this study aimed to elucidate the mechanisms of TFT against NAFLD in high-fat diet (HFD)-induced rats. Methods: This study utilized bioinformatics and network pharmacology to establish the active and potential ingredient-target networks of TFT. Furthermore, a protein–protein interaction (PPI) network was constructed, and enrichment analysis was performed to determine the key targets of TFT against NAFLD. Furthermore, an animal experiment was conducted to evaluate the therapeutic effect and confirm the key targets of TFT against NAFLD. Results: A total of 576 NAFLD-related genes were searched in GeneCards, and under the screening criteria of oral bioavailability (OB) ≥30% and drug-likeness (DL) ≥0.18, a total of 19 active ingredients and 210 targets were identified in TFT. Network pharmacology analysis suggested that 55 matching targets in PPIs were closely associated with roles for NAFLD treatment. Through the evaluation of network topology parameters, four key central genes, PPARγ, SREBP, AKT, and RELA, were identified. Furthermore, animal experiments indicated that TFT could reduce plasma lipid profiles, hepatic lipid profiles and hepatic fat accumulation, improve liver function, suppress inflammatory factors, and reduce oxidative stress. Through immunoblotting and immunofluorescence analysis, PPARγ, SREBP, AKT, and RELA were confirmed as targets of TFT in HFD-induced rats. Conclusion: In summary, our results indicate that TFT can prevent and treat NAFLD via multiple targets, including lipid accumulation, antioxidation, insulin sensitivity, and inflammation.

Objective:To investigate the effect of salvianolic acid C (SalC) on fibroblast-like synoviocytes and through the role of nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway.Methods:Rheumatoid arthritis-fibroblast-like synoviocytes (RA-FLSs) were exposed to different concentrations of SalC (0.1 μmol/L, 1 μmol/L, 5 μmol/L, 10 μmol/L, 20 μmol/L) for 24-72 h and measured for viability, proliferation, migration and invasion by Cell counting kit 8 (CCK-8) assay, wound-healing and transwell assay. The levels of Tumor Necrosis Factor-α (TNF-α), Interleukin-1 beta (IL-1β) and IL-6 were measured by enzyme linked immunosorbent assay (ELISA). Western blot was used to detect the expression of matrix metallopeptidase (MMP)-9, MMP-13, apoptosis-related proteins and Nrf2 mediated gene. Then we used ML385 to inhibit Nrf2 signaling pathway. RA-FLSs were measured for migration and invasion, and the expression of proteins related to apoptosis, inflammation and Nrf2 pathway.Results:Compared with the control group, SalC inhibited the cell migration significantly (0.1 μmol/L, 0.75±0.05, t=7.65, P<0.001; 5 μmol/L, 0.50±0.05, t=14.25, P<0.001; 10 μmol/L, 0.26±0.05, t=20.67, P<0.001) and invasion (0.1 μmol/L, 0.75±0.11, t=4.93, P<0.001; 5 μmol/L, 0.49±0.06, t=10.32, P<0.001; 10 μmol/L, 0.26±0.07 , t=14.96, P<0.001) of RA-FLs, reduced the levels of MMP-9 (0.1 μmol/L, 0.72±0.10, t=5.60, P<0.001; 5 μmol/L, 0.48±0.08, t=11.03, P<0.001; 10 μmol/L, 0.27±0.06, t=15.94, P<0.001) and MMP-13 (0.1 μmol/L, 0.77±0.06, t=8.66, P<0.001; 5 μmol/L, 0.58±0.06, t=11.03, P<0.001; 10 μmol/L, 0.32±0.13, t=14.22, P<0.001), and promoted apoptosis. SalC reduced the level of pro-inflammatory cytokines significantly ( P<0.001) and activated the expression of Nrf2 signaling pathway proteins Nrf2, CAT, NQO1, SOD1 and GSS ( P<0.001). After ML385 was used to interfere Nrf2, the levels of SalC on Nrf2 pathway proteins, such as Nrf2 (0.68±0.06, t=5.08, P<0.001), CAT (1.44±0.12, t=4.77, P<0.001), NQO1 (0.65±0.12, t=5.04, P<0.001), SOD1 (1.43±0.10, t=6.36, P<0.001) and GSS (1.42±0.10, t=7.60, P<0.001), as well as the levels of TNF-α [(260±22) pg/ml, t=13.75, P<0.001], IL-1β [(701±30) pg/ml, t=12.98, P<0.001], IL-6 [(180±10) pg/ml, t=16.38, P<0.001) were significantly reduced. In addition, ML385 inhibited the inhibition of SalC on cell migration and invasion (0.70±0.09, t=11.24, P<0.001; 0.64±0.04, t=8.03, P<0.001) and induction of apoptosis (24.4±1.8, t=23.02, P<0.001). Conclusion:SalC may inhibit cell activity and inflammatory response, promote apoptosis via the upregulation of Nrf2 signaling pathway. SalC may have therapeutic potential in RA. However, further investigation are needed in animal models and human.

Objective: To evaluate the tolerability and short-term efficacy of chemo-radiotherapy in 125 patients with stage ⅡB-ⅣA esophageal carcinoma after radical resection. Methods: We retrospectively evaluated the rate of completion, toxicity and survival of patients undergoing adjuvant concurrent chemo-radiotherapy after radical resection of esophageal carcinoma from January 2004 to December 2014 in our institution. The survival rate was determined by the Kaplan-Meier method and analyzed using the log-rank test. Multivariate prognostic analysis was performed using the Cox proportional hazard model. Results: 122 patients received more than 50 Gy dose (97.6%). A total of 52 patients received more than 5 weeks chemo-radiotherapy (41.6%), while 73 patients underwent only 1-4 weeks (58.4%). The median following up was 48.4 months. 8 patients lost follow up (6.4%). The 1-year and 3-year overall survival rate were 91.6% and 57.0%, respectively, with a median survival time of 64.4 months. The 1-year and 3-year disease free survival rate were 73.2% and 54.3%, respectively, with a median disease free survival time of 59.1 months. The most common acute complications associated with chemo-radiotherapy were myelosuppression, radiation esophagitis and radiation dermatitis, the majority of which were Grade 1-2. Of the 125 patients, there were 59 cases of recurrence, including 23 cases with local regional recurrence, 26 cases with hematogenous metastasis, and 8 cases with mixed recurrence. Univariate analysis showed that the numbers of concurrent chemotherapy was associated with the overall survival (P=0.006). But receiving more than 5 weeks was not the prognostic factor compared to 1 to 4 weeks chemotherapy (P=0.231). Multivariate analysis showed that only the numbers of concurrent chemotherapy was an independent prognostic factor (P=0.010). Conclusions Postoperative radiotherapy concurrent with weekly chemotherapy could improve the overall survival and decrease the recurrence for stage ⅡB-ⅣA esophageal carcinoma after radical resection. However, the completion rate of chemotherapy was low, so it was necessary to explore reasonable regimens to improve the completion rate and carry out prospective randomized controlled trial.

Objective To evaluate the tolerability and short?term efficacy of chemo?radiotherapy in 125 patients with stageⅡB?ⅣA esophageal carcinoma after radical resection. Methods We retrospectively evaluated the rate of completion, toxicity and survival of patients undergoing adjuvant concurrent chemo?radiotherapy after radical resection of esophageal carcinoma from January 2004 to December 2014 in our institution. The survival rate was determined by the Kaplan?Meier method and analyzed using the log?rank test. Multivariate prognostic analysis was performed using the Cox proportional hazard model. Results 122 patients received more than 50 Gy dose (97.6%). A total of 52 patients received more than 5 weeks chemo? radiotherapy (41.6%), while 73 patients underwent only 1?4 weeks (58.4%). The median following up was 48.4 months. 8 patients lost follow up ( 6.4%). The 1?year and 3?year overall survival rate were 91.6%and 57.0%, respectively, with a median survival time of 64.4 months. The 1?year and 3?year disease free survival rate were 73.2% and 54.3%, respectively, with a median disease free survival time of 59.1 months. The most common acute complications associated with chemo?radiotherapy were myelosuppression, radiation esophagitis and radiation dermatitis, the majority of which were Grade 1?2. Of the 125 patients, there were 59 cases of recurrence, including 23 cases with local regional recurrence, 26 cases with hematogenous metastasis, and 8 cases with mixed recurrence. Univariate analysis showed that the numbers of concurrent chemotherapy was associated with the overall survival (P＝0.006). But receiving more than 5 weeks was not the prognostic factor compared to 1 to 4 weeks chemotherapy (P＝0.231). Multivariate analysis showed that only the numbers of concurrent chemotherapy was an independent prognostic factor ( P ＝ 0.010 ). Conclusions Postoperative radiotherapy concurrent with weekly chemotherapy could improve the overall survival and decrease the recurrence for stage ⅡB?ⅣA esophageal carcinoma after radical resection. However, the completion rate of chemotherapy was low, so it was necessary to explore reasonable regimens to improve the completion rate and carry out prospective randomized controlled trial.

Objective To evaluate the tolerability and short?term efficacy of chemo?radiotherapy in 125 patients with stageⅡB?ⅣA esophageal carcinoma after radical resection. Methods We retrospectively evaluated the rate of completion, toxicity and survival of patients undergoing adjuvant concurrent chemo?radiotherapy after radical resection of esophageal carcinoma from January 2004 to December 2014 in our institution. The survival rate was determined by the Kaplan?Meier method and analyzed using the log?rank test. Multivariate prognostic analysis was performed using the Cox proportional hazard model. Results 122 patients received more than 50 Gy dose (97.6%). A total of 52 patients received more than 5 weeks chemo? radiotherapy (41.6%), while 73 patients underwent only 1?4 weeks (58.4%). The median following up was 48.4 months. 8 patients lost follow up ( 6.4%). The 1?year and 3?year overall survival rate were 91.6%and 57.0%, respectively, with a median survival time of 64.4 months. The 1?year and 3?year disease free survival rate were 73.2% and 54.3%, respectively, with a median disease free survival time of 59.1 months. The most common acute complications associated with chemo?radiotherapy were myelosuppression, radiation esophagitis and radiation dermatitis, the majority of which were Grade 1?2. Of the 125 patients, there were 59 cases of recurrence, including 23 cases with local regional recurrence, 26 cases with hematogenous metastasis, and 8 cases with mixed recurrence. Univariate analysis showed that the numbers of concurrent chemotherapy was associated with the overall survival (P＝0.006). But receiving more than 5 weeks was not the prognostic factor compared to 1 to 4 weeks chemotherapy (P＝0.231). Multivariate analysis showed that only the numbers of concurrent chemotherapy was an independent prognostic factor ( P ＝ 0.010 ). Conclusions Postoperative radiotherapy concurrent with weekly chemotherapy could improve the overall survival and decrease the recurrence for stage ⅡB?ⅣA esophageal carcinoma after radical resection. However, the completion rate of chemotherapy was low, so it was necessary to explore reasonable regimens to improve the completion rate and carry out prospective randomized controlled trial.

Objective To evaluate the efficacy of rescue treatment for recurrent esophageal cancer after radical esophagectomy, and to provide insights into the development of comprehensive treatment for esophageal cancer.Methods The clinical data of 218 patients who were confirmed with recurrent metastatic esophageal cancer after R0 resection and received rescue treatment in our hospital from 2004 to 2014 were retrospectively reviewed.The survival rate was determined by the Kaplan-Meier method.Univariate and multivariate prognostic analyses were performed using the log-rank test and Cox proportional hazards model, respectively.Results The median post-recurrence follow-up time was 53 months.The 1-and 3-year overall survival (OS) rates after recurrence were 57.2% and 24.4%, respectively.Among the 163 patients with local recurrence, the 1-and 3-year OS rates were 70% and 42% for patients treated with chemoradiotherapy (n=40), 55% and 24% for those with radiotherapy alone (n=106), and 23% and 8% for those with supportive therapy (n=13)(chemoradiotherapy vs.radiotherapy alone P=0.045, radiotherapy alone vs.supportive therapy P=0.004;none of the patients who were treated with chemotherapy alone survived for one year or more).Univariate analysis showed that N staging, TNM staging, and post-recurrence rescue treatment regimen were independent prognostic factors for esophageal cancer (all P=0.001).On the other hand, multivariate analysis indicated that only rescue treatment regimen was the independent prognostic factor for esophageal cancer (P=0.013).Conclusions Rescue chemoradiotherapy or radiotherapy alone can bring significant survival benefits for patients with recurrent and metastatic, especially locally recurrent, esophageal cancer following radical esophagectomy.

Objective To analyze the clinical value of postoperative radiotherapy for node-positive middle thoracic esophageal squamous cell carcinoma ( TESCC ) and to modify the target volume .Methods A total of 286 patients with node-positive middle TESCC underwent radical surgery in Cancer Hospital, Chinese Academy of Medical Sciences, from 2004 to 2009.In addition, 90 of these patients received postoperative intensity-modulated radiotherapy.The Kaplan-Meier method was used to calculate survival rates, and the log-rank test was used for survival difference analysis.The Cox model was used for multivariate prognostic analysis.The chi-square test was used for comparing the recurrence between patients receiving different treatment modalities.Results The 5-year overall survival ( OS) rates of the surgery alone ( S) group and surgery plus postoperative radiotherapy ( S+R) group were 22.9%and 37.8%, respectively, and the median OS times were 23.2 and 34.7 months, respectively ( P=0.003) .For patients with 1 or 2 lymph
node metastases (LNMs), the 5-year OS rates of the S group and S+R group were 27.3%and 44.8%, respectively ( P=0.017);for patients with more than 2 LNMs, the 5-year OS rates of the S group and S+R group were 16.7%and 25.0%, respectively (P=0.043).The peritoneal lymph node metastasis rates of N1 , N2 , and N3 patients in the S group were 2.9%, 10.9%, and 20.0%, respectively ( P=0.024) .The S+R group had a significantly lower mediastinal lymph node metastasis rate than the S group ( for patients with 1 or 2 LMNs:8.0%vs.35.3%, P=0.003;for patients with more than 2 LNMs, 10.0%vs.42.3%, P=0.001) , and had a prolonged recurrence time compared with the S group ( 25.1 vs.10.7 months, P=0.000) .However, for patients with more than 2 LNMs, the S+R group had a significantly higher hematogenous metastasis rate than the S group (46.7%vs.26.1%, P=0.039).Conclusions Patients with node-positive middle TESCC could benefit from postoperative radiotherapy.The target volume can be reduced for patients with 1 or 2 LNMs.Prospective studies are needed to examine whether it is more appropriate to reduce the radiotherapy dose than to reduce the target volume for patients with more than 2 LNMs.A high hematogenous metastasis rate warrants chemotherapy as an additional regimen.

Objective To evaluate 3.0 T MR DWI techniques in detecting the lesions of pre and post-radiofrequency ablation of the rabbit liver VX2 tumors. Methods Twenty two New Zealand white rabbits were used in this experiment. Twenty tumor fragments were implanted into the livers of 20 rabbits respectively. Two normal rabbits were used as controls for radiofrequency ablation of the normal liver. 3.0 T MR DWI was performed 14 to 21 days after tumor implantation (mean, 17 days) in the tumor-bearing animals. Radiofrequency ablation was performed in the 18 tumor-bearing animals and in the two healthy animals. 3.0 T MRI and DWI were performed 7 to 10 days after radiofrequency ablation (mean, 8 days).Pathology was obtained immediately after the completion of post-radiofrequency ablation MR imaging. The MRI features and ADC values of pre- and post -radiofrequency ablation lesions in the liyers with VX2 tumors and normal rabbits were analyzed and correlation was made with histopathologic findings. Analysis of variance repeated measures were performed in analyzing the differences among the ADC values of different tissues with the same b value. Results All 20 rabbit liver models of VX2 tumors were constructed successfully. One rabbit died of anesthetic overdose, another one showed necrosis within the implanted tumor. All 18 untreated VX2 tumors had predominantly low or iso-signal intensity on T1 WI and high signal intensity on T2WI. All 18 VX2 tumors and 2 normal rabbits were treated by radiofrequency ablation successfully. Lesions treated by Radiofrequency ablation displayed low signal intensity on T1 WI, and high signal intensity on T2WI. Seven to 10 days after radiofrequency ablation, lesions varied from having low signal intensity to slightly increased signal intensity on T1 WI, with areas of mixed ( high, intermediate, and low) signal intensity. A peripheral rim of high signal intensity with varying thickness on T2WI correlated with granulation tissue, which exhibited intense enhancement on contrast-enhanced images. Areas of low to intermediate signal intensity within the lesion on T2WI corresponded to coagulation necrosis. The tumor tissue appeared as areas of peripheral nedularity, with intermediate to high signal intensity on T2-weighted images and DWI. The tumor specimen was gray, among the tumor tissue, there were hyperplastic vessels,and granulation tissue. When b value was 600 s/mm2 , the ADC value of viable tumor (9 cases), necrosis (18 cases), granulation tissue ( 18 cases), normal liver tissue ( 18 cases) were ( 1. 227 ±0. 140) × 10-3,(0. 702 ± 0. 050)×10-3, ( 1.918 ± 0.124) × 10-3, ( 1. 739 ± 0. 044 ) × 10-3 mm2/s, respectively, which were statistically significant (P ＜0. 01 ). When b =200,400,600,800,1000 s/mm2, the differences of ADC values among viable tumor, granulation tissue, necrosis,normal liver tissue were also statistically significant ( P ＜0. 01 ). Conclusion The rabbit liver VX2 tumor models and 3.0 T MR DWI are important tools in the basic and clinical researches of radiofrequency ablation.

ranches of portal vein were found in 3 cases. Conclusion The multi-slice spiral CT findings of eosinophilie hepatic infiltration are relatively specific, and three-phase dynamic CT studies can be a valuable tool for the diagnosis of this disease.

Objective To explore the reproducibility of normal hepatic MRS at 3.0T. Methods The hepatic proton MRS was performed with GE Signa Excite HD 3.0T system and eight-channel torso phased-array coils using PRESS sequence. Thirty-one healthy individuals were enrolled in this study. Liver spectra were collected with TR of 1500 ms, TE of 30 ms, ROI of 2 cm×2 cm×2 cm, NSA of 64 times. The outcomes were statistically analyzed with Wilcoxon signed ranks test and Spearman correlation test.Results There was no significant difference of signal to noise ratio (Z=-0.535,P=0.593), baseline stability (Z=-0.333, P=0.739), linewidth of automatic shimming (Z=-0.305, P=0.761), water suppression (Z=-1.232, P=0.218), height of lipid peak (Z=-0.558,P=0.557), area under the lipid peak (Z=-1.195,P=0.232), height of water peak (Z=-0.647,P=0.518) and area under the warter peak (Z=-0.118, P=0.906) between first examination and second examination. Correlation coefficient of the former and the later measurements of lipid area and water area were 0.784 (P<0.001) and 0.799 (P<0.001), respectively.Conclusion The reproducibility is good for in vivo liver proton MRS at 3.0T.