1.Effect of ghrelin on proliferation and mitofusin-2 expression of human aortic smooth muscle cells
Yongming HE ; Mingbao SONG ; Jianbo HU ; Yuanping ZHANG ; Youmei LI
Chongqing Medicine 2017;46(15):2034-2036
Objective To investigate the effects of ghrelin on proliferation of vascular smooth muscle cells(VSMC)and the expression of mitochondrial fusion 2(Mfn-2)in cultured human aortic smooth muscle cells(HASMCs).Methods HASMCs were cultured in vitro,treated with different concentrations(10-9,10-8,10-7,10-6,10-5 mol/L)ghrelin or 10-6 mol/L ghrelin for different time(0,6,12,18,24 h).Subconfluent HASMCs at passage 4-6 were used in experiments.MTT essay was used to investigate the effect on proliferation of HASMCs.RT-PCR and Western blot were used to analyse the expression of Mfn-2.Results 10-7-10-5 mol/L ghrelin inhibited the proliferation of HASMCs,and the inhibitory effect of concentration of 10-6 mol/L was the most obvious(P<0.01).Ghrelin inhibited the proliferation of HASMCs in 6-24 h,and it reached the peak at 24 h(P<0.01).10-6 mol/L ghrelin significantly increased the expression of Mfn-2 mRNA and protein(P<0.01).The up-regulation of 10-6 mol/L ghrelin on Mfn-2 mRNA and protein expression reached the peak at 18 h(P<0.01).Conclusion Ghrelin might inhibit the proliferation of HASMC by up-regulating the expression of Mfn-2.
2.Preliminary comparative study between elective nodal irradiation and involved field radiation therapy for clinical early-stage esophageal carcinoma
Wenbin SHEN ; Hongmei GAO ; Shuchai ZHU ; Youmei LI ; Juan LI ; Jinwei SU ; Zhikun LIU ; Xuguang LI
Chinese Journal of Clinical Oncology 2013;(17):1047-1050
Objective: This study was performed to analyze the feasibility of elective nodal irradiation (ENI) for early-stage esophageal carcinoma (EEC), evaluate the curative effect of radiation therapy for EEC, and determine the causes of treatment failure. Methods:Data were collected from 123 patients with esophageal squamous cell carcinoma of clinical T1-2 N0-1 M0 stage. Patients were divided into two groups based on different types of radiation therapy. Among the 123 patients, 102 underwent involved field irradiation (IFI), whereas 21 received ENI. A comparative analysis of patients in the two groups was conducted. Results:In 123 patients, the one-, three-, and five-year overall survival rates were 87.8%, 47.2%, and 36.6%, respectively. By contrast, the one-, three-, and five-year local control rates were 89.4%, 67.5%, and 48.8%, respectively. After comparing the one-, three-, and five-year survival rates in the ENI patients (i.e., 90.5%, 47.6%, and 42.9%, respectively) with those in the IFI patients (i.e., 86.3%, 49.0%, and 35.2%, respectively), no significant difference was found (χ2=0.290, P=0.588 8). The results indicate that ENI possibly decreased nodal metastases (χ2=5.778, P=0.016). Conclusion:Three-dimensional conformal radiotherapy is one of the best therapeutic regimens of radiation for EEC. ENI is possibly effective for preventing regional nodal metastasis. Whether ENI leads to an improved overall survival needs further investigation.
3.Three-dimensional conformal radiotherapy of early stage esophageal carcinoma
Wenbin SHEN ; Shuchai ZHU ; Juan LI ; Jingwei SU ; Zhikun LIU ; Youmei LI
Chinese Journal of Radiation Oncology 2011;20(1):32-35
Objective To analyze the result of3-dimensional conformal radiotherapy(3DCRT)and operation of early stage esophageal carcinoma. Methods Ninety-three patients with early stage esophageal carcinoma were treated with 3DCRT from October 2000 to December 2006. The total dose was 50 -70 Gy/25 -35F/5 -7 w. Toxicities and survival rates were evaluated by Kaplan Meier method and the factors of death were analyzed. Results In the 3DCRT group, 79, 42 and 13 cases were followed up for at least 1-,3-,and 5-year, respectively. Follow-up rate was 100%. The 1-, 3-, and 5-year actuarial survival rates were 84% ,50% and 29%, respectively, with a median survival time of 37.0 months. The 1-, 3-, and 5-year local control rates were 83% ,63% and 55% ,respectively. The 1-, 3-, and 5-year disease free survival rates were 83% ,49% and 28%, respectively. The 1-, 3-, and 5-year metastasis free survival rates were 84%,51% and 28%, respectively. There were significant influence on the prognosis of age, the state of food taken before treatment, the pain of chest and back, the disease region, the tumor length in x-ray, the maximuminfiltration depth in CT scan, the preliminary curative effect and the no operation in univariate analysis. The Cox multivariate model showed that age, the pain of chest and back, the disease region and the tumor length in X-ray were independent prognostic factors. In the operation group, 80,46 and 16 cases were followed up for at least 1-,3-,and 5-year, respectively. Follow-up rate was 100%. The 1-, 3-, and 5-year actuarial survival rates were 86% ,62% and 41%, respectively, with a median survival time of 47.8 months. Conclusion Three-dimensional conformal radiotherapy is one of the best radiation treatment regimen for early esophageal carcinoma.
4.Analysis of the rule of lymph node metastasis and evaluation of the consistence of preoperative computed tomographic findings and postoperative pathologic diagnosis for thoracic esophageal carcinoma
Shuchai ZHU ; Changliang SONG ; Zhikun LIU ; Qian XU ; Youmei LI ; Juan LI
Chinese Journal of Radiation Oncology 2011;20(1):28-31
Objective To analyze the rule of lymph node metastasis, compare the preoperative computed tomographic findings with pathological diagnosis in thoracic esophageal carcinoma and to evaluate the clinical value. Methods Six hundred and eighteen patients with esophageal carcinoma after radical resection were enrolled. All patients did not receive any preoperative radiotherapy or chemotherapy, having complete information of postoperative pathological reports. CT scanning were applied to all patients in our hospital. The CT image were transmitted to the three-dimensional treatment planning system via the network at digital format and be reconstructed. In which system the sensitivity, specificity and accuracy rates in diagnosis of lymph node metastasis of the preoperative CT image were observed, measured and recorded. x2 test or Fisdher's statistical methods was adopted for comparing the concord rate of preoperative CT scanning with postoperative pathological diagnosis. Results Lymph nodes metastasis were defected in 242 of the 618 treated patients(39.2%), The rate of lymph node metastasis present in lower neck, upper-mediastinum,middle-mediastinum, lower-mediastinum, and superior abdomen regions in upper-thoracic esophageal carcinoma were 3.2% ,20.8% ,6.4% ,2.4% and 8.0%, in middle-thoracic esophageal carcinoma 1.5%,7.8% ,22.0% ,3.5% and 22.8%, and in lower-thoracic esophageal carcinoma 0% ,2.0% ,21.4% ,6.1% and 32.7%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value,younden index and accuracy rates of diagnosis of lymph node metastasis with preoperative CT scan were 58.3%, 70.7%, 56.2%, 72.5%, 29.0% and 65.9%, respectively. The concordance rate of 0, 1, 2 and ≥ 3 lymph node metastasis by preoperative CT scanning with postoperative pathological diagnosis were 72.4%, 32.2% , 58.3% and 73.1%, respectively in whole group(x2 = 82. 61, P = 0.000). The concordance rate of no lymph node metastasis by CT scan comparing with that by postoperative pathological diagnosis was higher than that of the 1 lymph node metastasis in upper-thoracic esophageal carcinoma 3 lymph node metastasis were 71.1%, 30.1%, 55.6% and 77.8%, respectively(x2 =55.14,P =0.000.Conclusions Preoperative CT image can accurately predict the distribution patterns of the lymph node metastasis in esophageal carcinoma. The concordance rate was the highest in diagnosis of 0 and ≥3 lymph node metastasis, the lowest in diagnosis of one lymph node metastasis. These findings are valuable for definition of the target range of radiotherapy after radical resection of esophageal carcinoma.
5.The dose study of radiation gastritis caused by esophageal cancer radical postoperative prophylactic irradiation
Wenbin SHEN ; Hongmei GAO ; Shuchai ZHU ; Youmei LI ; Yankun CAO ; Shuguang LI ; Shiwang WEN ; Hui ZHU
Chinese Journal of Radiation Oncology 2016;25(8):818-822
Objective To study the relationship between radiation gastritis ( RG ) caused by esophageal cancer radical postoperative prophylactic IMRT and the dose of gastric. Methods A total of 49 esophageal cancer patients received postoperative adjuvant radiatherapy after esophagectomy, we analysised the dose?volume histogram of treatment plan and the the occurrence of RG, To analysis those physical indicators may be related to the occurrence of RG. The of ROC curve to analysis the physical index of the occurrence of acute radiation gastritis, Chi square test is compared between groups, Logistic method was used to multivariate analysis. Results The whole group, a total of 19 cases ( 39%) patients with symptoms of acute RG level 2 or higher. The results of ROC curve analysis showed that the physical variables associated with the occurrence of RG include stomach Max,stomach Mean,LSTT5?LSTT40 and V5?V50.According to the ROC curve,the cutoff values of the physical parameters of the patients were grouped. The incidence of acute≥2RG in the group of above boundary value patients significantly higher than below boundary value group, the physical index of the differences between groups were significant (P=0. 000?0. 022),except V5.The results of Logistic multivariate analysis showed that LSTT5 and V40 were independent predictor of≥2 RG (P=0. 026,0. 001). Conclusions According to the results of this study,We should pay attention to the protection of the stomach in develop a treatment plan for the prevention of postoperative patients with esophageal cancer,dose?volume histogram can well predict the occurrence of RG. Stomach LSTT5 and V40 were independent predictor of≥2 RG.The results of this study need to be further studied.
6.Effect of RNAi targetingBMI-1 gene on radiosensitivity of esophageal carcinoma cells
Xingxiao YANG ; Youmei LI ; Heng SONG ; Zhikun LIU ; Ming MA ; Shuchai ZHU
China Oncology 2016;26(9):763-769
Background and purpose:B cell-specific MLV integration site 1 (BMI-1) gene plays an important role in DNA damage after exposure to irradiation. The present study aimed to investigate the effect ofBMI-1 on radio-sensitivity of esophageal carcinoma cell after down-regulation of BMI-1 expression by silencing siRNA.Methods:Three pairs of siRNA based on the sequences of the BMI-1 mRNA were synthesized (siRNA1, siRNA2 and siRNA3) by compa-ny, and transfected into cultured TE13 cells as the BMI-1 siRNA groups, and a negative one was synthesized to be used as the negative control (NC) group. The untransfected group was named as the control group. BMI-1 mRNA and protein expression in esophageal cancer TE13 cells were detected by reverse transcription polymerase chain reaction (RT-PCR) and Western blot in different groups. This study used flow cytometry assay to analyze cell cycle of transfected cells, and examined cellular growth and radiosensitivityin vitro by MTT and clone formation assay. mRNA and protein expression of p16 and CDK4 in esophageal cancer TE13 cells were detected by RT-PCR and Western blot.Results:The results of RT-PCR and Western blot showed that the expressions of BMI-1 at gene and protein levels were inhibited after silencing the BMI-1 gene. The mRNA and protein expression of BMI-1 in BMI-1 siRNA3 group were both significantly lower than that in BMI-1 siRNA1 and 2 groups. There was no significant difference in the cell proliferation among control, NC and BMI-1 siRNA3 groups. The values ofD0,Dq, and SF2 in BMI-1 siRNA3 group were 1.761, 2.122 and 0.6255, respectively, obvi-ously lower than those in control group (2.514, 2.694 and 0.8268) and those in NC group (2.506, 2.664 and 0.8231), while the value of N in BMI-1 siRNA3 group (3.336) was higher than that in control group (2.92) and that in NC group (2.895), which showed higher radiosensitivity in BMI-1 siRNA3 group. In addition, the cell cycle was arrested at G2/M phase after irradiation in control and NC groups. The percentage of G0/G1 phase in BMI-1 siRNA3 group was higher than that of control group and NC group, while the percentage of G2/M phase was lower than those in the latter. The up-regulation of p16 and down-regulation of CDK4 at gene and protein levels were detected after knockdown of BMI-1 expression by siRNA (P<0.01).Conclusion:siRNA could inhibitBMI-1 gene expression in esophageal cancer TE13 cells and enhance radiosensitivity, followed by eliminating the cell cycle arrest at G2/M stage after irradiationin vitro, which is related to the regulation of the protein expression ofp16 andCDK4.
7.Preparation and release behaviour of mesoporous silica/ethylcellulose sustained-release mini-matrix.
Qiaoli WU ; Guilan QUAN ; Yu HONG ; Linna WU ; Youmei ZENG ; Ge LI ; Xin PAN ; Chuanbin WU
Acta Pharmaceutica Sinica 2015;50(4):492-9
Hot-melt extrusion was applied to prepare mesoporous silica/ethylcellulose mini-matrix for sustained release, and fenofibrate was used as a model drug, ethylcellulose and xanthan gum were chosen as sustained-release agent and releasing moderator, respectively. This novel matrix obtained the controlled release ability by combining mesoporous silica drug delivery system and hot-melt extrusion technology. And mesoporous silica particle (SBA-15) was chosen as drug carrier to increase the dissolution rate of fenofibrate in this martix. Scanning electron microscope, transmission electron microscope, small angle X-ray powder diffraction and N2 adsorption-desorption were introduced to determine the particle morphology, particle size and pore structure of the synthesized SBA-15. The results showed that SBA-15 had a very high Brunauer-Emmett-Teller specific surface area, a narrow pore size distribution, large pore volume and a ordered two-dimensional hexagonal structure of p6mm symmetry. Differential scanning calorimetry and X-ray powder diffraction results demonstrated that fenofibrate dispersed in an amorphous state inside the pores of the mesoporous silica which contributed to the improvement in the dissolution rate. The drug release of mini-matrices was influenced by ethylcellulose viscosity grades and xanthan gum concentration, which increased with the increasing of xanthan gum concentration and decreasing of ethylcellulose viscosity. Mini-matrix containing 22% xanthan gum exhibited a good sustained release performance, and the drug release behavior followed the first-order kinetics.
8.Drug Resistance and Gene Distribution of Klebsiella pneumoniae Producing the Ultra-broad Spectrum Beta-lactam Enzyme
Xiaomei LAI ; Lin LI ; Youneng GUO ; Jia FANG ; Youmei XU ; Xiangchun FU ; Wei TANG
Chinese Journal of Nosocomiology 2009;0(18):-
OBJECTIVE To investigate the epidemic,drug resistance and gene distribution of ESBLs-producing Klebsiella pneumoniae (KPN) from Jiangxi TCM Hospital. METHODS The susceptibility of KPN was detected by MIC PCR was used to detect ESBLs gene. RESULTS There were 42 strains with ESBLs isolated,the positive rate was 35.0%. The drug resistance rate of KPN with ESBLs was higher than that without ESBLs,PCR typing result:TEM 33 (78.6%),SHV 8 (19.0%) and CTXM 29 (69.0%). CONCLUSIONS The ESBLs-producing bacteria have multiple drug resistant genes;TEM and CTXM are the main drug resistant genes in our hospital.
9.Effect of postoperative adjuvant therapy on the prognosis of patients with stage pT3N0M0 thoracic esophageal squamous cell carcinoma:a preliminary analysis
Wenbin SHEN ; Hongmei GAO ; Shuchai ZHU ; Teng LI ; Shuguang LI ; Youmei LI ; Zhikun LIU ; Juan LI ; Jingwei SU
Chinese Journal of Radiation Oncology 2017;26(8):867-873
Objective To determine the prognostic factors in patients with stage pT3N0M0 thoracic esophageal squamous cell carcinoma (TSCC) after esophagectomy, and to compare the effects of different treatment modalities on the prognosis of patients.Methods A retrospective analysis was conducted on 480 patients with stage pT3N0M0 TSCC from 2007 to 2010 to determine the prognostic factors in the patients, and to compare the effects of different treatment modalities on their prognosis.Survival rate was calculated using the Kaplan-Meier estimator, and multivariate analysis of prognostic factors was performed using the Cox model.Results Of the 439, 333, and 278 patients who completed the 1-, 3-, and 5-year follow-up, respectively, the 1-, 3-, and 5-year overall survival (OS) rates were 90.0%, 68.7%, and 57.9%(median 87 months, 95% confidence interval (CI=74.7-99.4), respectively, and the 1-, 3-, and 5-year disease-free survival (DFS) rates were 82.3%, 60.4%, and 52.3%(median 71.3 months, 95%CI=55.1-87.5), respectively.In order to account for the different constituent ratios of some clinical and pathological data between the three groups of patients, 55 patients in each group were matched using propensity score matching (PSM)(all P>0.05).It was found that the post-PSM 1-,3-, and 5-year OS and DFS were significantly different between patients who received surgery only, postoperative chemotherapy (POCT), and postoperative chemoradiotherapy/radiotherapy (POCRT/RT)(P=0.000 and 0.006,respectively).Multivariate Cox analysis showed that age, lesion location, and treatment modality were independent prognostic factors for OS and DFS (P=0.029,0.004,0.000 and P=0.009,0.003,0.002), and the length of lesion was also an independent prognostic factor for DFS (P=0.003).Conclusions Although the rate of post-operative treatment failure is still high among patients with stage pT3N0M0 TSCC, POCRT/PORT can improve the prognosis and the 5-year OS and DFS of these patients.However, further large-sample prospective studies will be required to confirm these findings.
10.Analysis of postoperative failure model in patients with stage pN0 esophageal squamous cell carcinoma and its effect on postoperative radiotherapy
Wenbin SHEN ; Hongmei GAO ; Shuchai ZHU ; Teng LI ; Shuguang LI ; Youmei LI ; Zhikun LIU ; Juan LI ; Jingwei SU
Chinese Journal of Radiological Medicine and Protection 2017;37(3):199-204
Objective To investigate the failure model of patients with stage pN0 thoracic esophageal squamous cell carcinoma (TESCC) after surgery alone and to discuss the feasibility of postoperative radiotherapy.Methods A retrospective analysis was performed on 473 patients with TESCC who received surgery alone from January 2007 to December 2010.The feasibility of adjuvant radiotherapy for pN0 TESCC patients was investigated through the failure model of postoperative patients.Results Of all patients,there were 57 cases with chest-regional recurrence (12.1%),most of which occurred in the mediastinal lymph nodes(52 case).There were 42 (8.9%) patients were identified as distant metastasis (DM),of which 13 cases were found to have both local recurrence and DM,and the total failure rate was 20.9%.The chest-regional recurrence rate of upper TESCC was statistically significantly higher than middle and lower (x2 =7.469,P < 0.05),but DM rate had no statistically significant difference (P > 0.05).The chest-regional recurrence rate and DM rate of the advanced T stage were significantly higher than those of the early T stage(x2 =10.247,7.886,P < 0.05).The result of univariate analysis showed that disease site,the degree of adhesion,postoperative stump were significant factors of chestregional recurrence rate (x2 =14.232,9.486,7.546,P < 0.05).Gender,smoking and preoperative weight loss ≥5 kg significantly influenced DM (x2 =10.823,10.275,6.065,P < 0.05).In addition,the T stage was the significant influence factor of chest-regional recurrence and DM(x2 =15.994,12.885,P <0.05).The result of multivariate analysis showed that T stage and postoperative stump were independent factors of chest-regional recurrence (P < 0.05).Smoking was an independent factor of DM (P < 0.05).Conclusions There was a high rate of chest-regional recurrence in patients with stage pN0 TESCC who received surgery alone.Postoperative radiotherapy was recommended for patients with upper TESCC,advanced T stage,severe local adhesion,positive margin in and postoperative stump.Male,smoking and preoperative weight loss≥5 kg were associated with higher DM rate.