ObjectiveTo evaluate the prognostic significance of serum levels of vascular endothelial growth factor (VEGF) and insulin-like growth factors-Ⅰ (IGF-Ⅰ) in advanced gastric cancer patients who were treated with oxaliplatin/5-fluorouracil (FOLFOX). MethodsNinety-six advanced gastric cancer patients who were treated with FOLFOX in our hospital between March 2007 to August 2010 were enrolled in this study. All of the patients were treated with oxaliplatin (85 mg/m2) as a 2-hour infusion on day 1, and leucovorin (20 mg/m2, about 10 min) on day 1 and day 2, followed by a 5-fluorouracil bolus (400 mg/m2) and 22 hours of continuous infusion of 600 mg/m2. Treatment was repeated in 2-week intervals, and patients received 4 chemotherapy cycle in total. The levels of serum VEGF and IGF-Ⅰ were measured using enzyme-linked immunoassays. The relationship between serum levels of VEGF/IGF-Ⅰ and the clinicopathological characteristics of patients, the relationship between serum levels of VEGF/IGF-Ⅰ and prognosis of patients, were analyzed. ResultsThe serum levels of VEGF and IGF-Ⅰ were (464.4±57.4) pg/mL and (33.5±7.3) ng/mL, respectively. The serum level of VEGF was related with surgical history, Lauren's classification, TNM staging before treatment, and pathological type (P < 0.05), and serum level of IGF-Ⅰ was related with TNM staging before treatment and number of transferred organs (P < 0.05). The serum levels of VEGF and IGF-Ⅰ in stable disease (SD) +progressive disease (PD) patiens were higher than those of complete response (CR) +partial response (PR) patients (P < 0.05). The results of Cox proportional hazard regression model showed that, effect of chemotherapy (HR=1.764, P=0.006), number of transferred organs (HR=1.662, P=0.015), serum level of VEGF (HR=1.834, P=0.012) and IGF-Ⅰ (HR=1.855, P=0.008), were all significantly related with time to progression (TTP); serum level of VEGF (HR=2.205, P=0.002) and IGF-Ⅰ (HR=1.931, P=0.004) were all significantly related with overall survival (OS). ConclusionLevels of serum VEGF and IGF-Ⅰ are independent prognostic factors in patients with advanced gastric cancer who were treated with FOLFOX chemotherapy.
Objective To investigate efficacy and toxicity of XELOX or FOLFOX4 regimen as neoadjuvant concurrent chemoradiotherapy for stage Ⅱ/Ⅲ middle and low rectal cancer. Methods From June 2011 to March 2014, 120 patients with stage Ⅱ/Ⅲ middle and low rectal cancer who underwent the surgical treatment were enrolled in The Fifth People’s Hospital of Qinghai Province, then were randomly divided into radiotherapy+FOLFOX4 regimen group and radiotherapy+XELOX regimen group. The radiotherapy and chemotherapy were performed simultaneously before the radical resection of rectal cancer. Three-dimensional conformal radiotherapy: 1.8–2.0 Gy/times, 5 times/week, a total of 25 times, the total dose was 45.0–50.0 Gy. At the same time, 2 cycles of chemotherapy were performed according to the FOLFOX4 program (oxaliplatin+leucovorin+5-fluorouracil) or XELOX regimen (capecitabine tablet+oxaliplatin). The radical surgery was performed on 4 to 8 weeks after the preoperative chemoradiotherapy, then 8 to 12 cycles of FOLFOX4 chemotherapy and 4 to 6 cycles of XELOX chemotherapy were completed in the radiotherapy+FOLFOX4 regimen group and the radiotherapy+XELOX regimen group respectively on 1 month after the radical surgery. The curative effect and the occurrence of acute toxicity were observed. Results ① There were no significant differences in thegeneral data such as the gender, age, cT stage, cN stage, TNM stage, histological type, differentiation degree, etc. between the two groups(P>0.05). ② The reduced staging rates of cT and cN in the radiotherapy+XELOX regimen group was 63.3% (38/60) and 86.7% (52/60), respectively, which was significantly higher than that in the radiotherapy+FOLFOX4 regimen group〔38.3% (23/60) and 53.3% (32/60), respectively〕 , the differences were statistically significant (P<0.05). ③ The complete response rate and the effective rate (complete response rate+partial response rate) in the radiotherapy+XELOX regimen group were significantly higher than those in the radiotherapy+FOLFOX4 regimen group (P<0.05). ④ The overall 3-year survival rate in the radiotherapy+XELOX regimen group was significantly higher than that in the radiotherapy+FOLFOX4 regimen group (P<0.05). There were no significant differences in the 3-year disease-free survival rate, distant metastasis rate, and local recurrence rate between the two groups (P>0.05). ⑤ All the patients suffered from 3 to 4 degrees toxicities, however, the incidence rates of the overall toxicity and the diarrhea toxicity in the radiotherapy+XELOX regimen group were significantly lower than those in the radiotherapy+FOLFOX4 regimen group (P<0.05). Conclusion Preliminary results of limited cases in this study show that XELOX regimen is more effective and less acute toxicity than FOLFOX4 regimen for preoperative concurrent chemoradiotherapy for patients with stage Ⅱ/Ⅲ middle and low rectal cancer.
ObjectiveTo evaluate the physical and chemical properties, immunogenicity, and osteogenesis of two antigen-extracted xenogeneic bone scaffolds—decalcified bone matrix (DBM) and calcined bone.MethodsBy removing the inorganic and organic components of adult pig femus, xenogeneic DBM and calcined bone were prepared respectively. The density and pH value of the two materials were measured and calculated, the material morphology and pore diameter were observed by scanning electron microscope, and the surface contact angle was measured by automatic contact angle measuring instrument. The safety, osteogenic activity, and immunogenicity of the two materials were evaluated by cytotoxicity test, osteoblast proliferation test, DNA residue test, and human peripheral blood lymphocyte proliferation test. The two materials were implanted into the 5 mm full-thickness skull defect of 6-week-old male Sprague Dawley rats (the blank control group was not implanted with materials). The materials were taken at 4 and 8 weeks after operation, the repair effect of the materials on the rat skull was observed and evaluated by gross observation, Micro-CT scanning, and HE staining observation.ResultsCompared with calcined bone, DBM has lower density and poor hydrophilicity; the pH value of the two materials was 5.5-6.1, and the pore diameter was 160-800 μm. The two materials were non-cytotoxic and could promote the proliferation of osteoblasts. The absorbance (A) values of osteoblast proliferation at 1, 4, and 7 days in the DBM group were significantly higher than those in the calcined bone group (P<0.05). The DNA residues of the two materials were much lower than 50 ng/mg dry weight, and neither of them could stimulate the proliferation and differentiation of human peripheral blood lymphocytes. The results of animal experiments in vivo showed that the bone volume/total volume (BV/TV) in DBM group and calcined bone group were significantly higher than that in blank control group at 4 weeks after operation (P<0.05), and that in calcined bone group was significantly higher than that in DBM group (P<0.05); at 8 weeks after operation, there was no significant difference in BV/TV between groups (P>0.05). HE staining showed that at 4 and 8 weeks after operation, the defect in the blank control group was filled with fibrous connective tissue, the defect was obvious, and no bone growth was found; the defect in DBM group and calcined bone group had been repaired to varying degrees, and a large number of new bone formation could be seen. The material degradability of DBM group was better than that of calcined bone group.ConclusionThe physical and chemical properties and degradability of the two kinds of xenogeneic bone scaffolds were slightly different, both of them have no immunogenicity and can promote the repair and reconstruction of skull defects in rats.
Glaucoma is the leading cause of irreversible blindness, but its early symptoms are not obvious and are easily overlooked, so early screening for glaucoma is particularly important. The cup to disc ratio is an important indicator for clinical glaucoma screening, and accurate segmentation of the optic cup and disc is the key to calculating the cup to disc ratio. In this paper, a full convolutional neural network with residual multi-scale convolution module was proposed for the optic cup and disc segmentation. First, the fundus image was contrast enhanced and polar transformation was introduced. Subsequently, W-Net was used as the backbone network, which replaced the standard convolution unit with the residual multi-scale full convolution module, the input port was added to the image pyramid to construct the multi-scale input, and the side output layer was used as the early classifier to generate the local prediction output. Finally, a new multi-tag loss function was proposed to guide network segmentation. The mean intersection over union of the optic cup and disc segmentation in the REFUGE dataset was 0.904 0 and 0.955 3 respectively, and the overlapping error was 0.178 0 and 0.066 5 respectively. The results show that this method not only realizes the joint segmentation of cup and disc, but also improves the segmentation accuracy effectively, which could be helpful for the promotion of large-scale early glaucoma screening.
ObjectiveTo investigate the expression and pathological significance of neutrophil elastase (NE) and mucin 5AC (MUC5AC) in chronic obstructive pulmonary disease (COPD) rats. MethodsA total of 60 male specific pathogens free Sprague-Dawley rats were randomly divided into model group and blank group, each with 30 rats. The number of goblet cells and the positive expression of NE and MUC5AC were compared between the two groups by hematoxylin-eosin staining, alcianblue-periodic acid Schiff staining and immunohistochemical staining. ResultsNo rats died accidentally during the experiment. The number of goblet cells was 57.93±7.79 in the model group and 6.80±3.19 in the blank group, and the difference between the two groups was statistically significant (t=−44.267, P<0.05). The median (lower quartile, upper quartile) of the positive expression score of NE was 0 (0, 0) in the blank group and 2 (2, 3) in the model group, the median (lower quartile, upper quartile) of the positive expression score of MUC5AC was 0 (0, 1) in the blank group and 2 (2, 2) in the model group, and the differences between the two groups were statistically significant (P<0.05).ConclusionsThe positive expression of NE, goblet cells, MUC5AC and mucus secretion in COPD model rats increases significantly. Perhaps NE and MUC5AC can be used as target interventions to inhibit mucus hypersecretion.
ObjectiveTo investigate the correlation between the content of bone morphogenetic protein 2 (BMP-2) in demineralized bone matrix (DBM) and its osteogenic activity in vitro and in vivo, in order to choose a simple and convenient method to evaluate the osteogenic activity of DBM.MethodsThe left mid-femoral tissues of 9 donors were taken, and DBMs (S1-S9) were prepared by dynamic decalcification process, and inactivated DBM (control group) was prepared at the same time. Protease inhibitor method, collagenase method, guanidine hydrochloride/ethylene diamine tetraacetic acid (EDTA) method, and RIPA lysate method were used to extract BMP-2 in S1-S9 and inactivated DBMs. The BMP-2 content was measured and the differences between DBMs were compared. Then the S1-S9 and inactivated DBMs were co-cultured with mouse embryonic osteoblasts MC3T3-E1, respectively. The cell proliferation was detected by MTT method and fluorescence staining, and alkaline phosphatase (ALP) activity was detected at the same time. Thirty BALB/c male nude mice were divided into 10 groups, namely S1-S9 DBM groups (S1-S9 groups) and inactivated DBM group (control group), with 3 mice in each group. Muscle pockets of the middle thighs were prepared on both hindlimbs of mice in each group, and implanted corresponding DBM materials. At 4 weeks after operation, the samples were taken for HE staining observation and semi-quantitative evaluation, and the new bone formation score was calculated.ResultsThe BMP-2 content of DBM derived from different donor bones was distinct. The BMP-2 content obtained by different extraction methods for DBM prepared from the same donor bone was also different, and the extraction efficiency of the guanidine hydrochloride/EDTA method was the highest. In vitro cell experiments, MTT test displayed that cell proliferations and ALP activity were significantly higher in S4 and S6 groups than in other groups at each time point after co-cultivation (P<0.05). Moreover, the cell proliferation of S4 group was the most significant at 7 days (P<0.05); fluorescence staining demonstrated that the osteoblasts of each group was in good condition, but the osteoblasts of S1, S2, S3, S4, and S6 groups were significantly more than other groups. In vivo ectopic osteogenesis experiments, the cartilage and new bone formation could be seen in the bone graft area of S1-S6 groups at 4 weeks after operation, and with the increase of BMP-2 content, the more new bone formation induced by the material, the higher the score of new bone formation of the material (P<0.05). Among them, S4 and S6 groups contained a large number of chondrocytes and osteoblasts in the osteogenesis area.ConclusionThe osteogenic activity of DBM can be evaluated through BMP-2 quantitative detection combined with in vitro osteoblast proliferation and differentiation experiments.