Objective To evaluate the prognostic value of fluorodeoxyglucose (FDG) standardized uptake value (SUV) of positron emission tomography (PET) before radiotherapy in non-small cell lung cancer (NSCLC) treated with three-dimensional conformal radiation therapy (3DCRT). Methods Seventy-three patients with stage Ⅲ NSCLC underwent PET to calculate SUV within 2 weeks before 3DCRT. The a-nalysis was carried out after the irradiation of 60 -66 Gy. The possible prognostic factors were assessed by Cox proportional hazards model. Results The mean SUV for squamous cell carcinoma, adenocarcinoma and others were 16.94, 14.40 and 6.33, respectively (F = 0. 51, P = 0. 604). The mean SUV for tumor volume less than and more than 50 cm~3 was 13.81 and 20.18 (F = 7.54, P = 0. 008). In the univariate analysis, a cutoff SUV of 17 and chemotherapy were correlated with the prognosis. In the multivariate analysis, SUV was the only independent prognostic factor (relative risk = 2.61). Conclusions SUV is a prognostic factor in patients with NSCLC treated by 3DCRT, which deserves further studies.

Objective To study the radiation sensitive enhancement ratio (SER) of NS398 on esophageal cancer stem cells and adherent tumor cells and analyze the radioresistance related protein expressions.Methods ECA109 esophageal cancer stem cells were cultured in serum-free medium.Expression levels of cell surface maker CD44 + and CD271 + were analyzed by flow cytometry.MTT assay was used to detect cell proliferation after the treatments with NS398 and irradiation(0,4 and 8 Gy).The sensitization effects of NS398 on the parental cells and its spheroid were evaluated by clone formation assay.Western blot assay was performed to determine protein expressions.Results Serum-free medium was successfully applied to isolate the cancer stem cells with spherical properties.CD271 + in the spheroid cells was notable higher than that in the parent cells (t =3.81,P ＜ 0.05).After irradiation,the proliferation rate of parental cells was higher than that in spheroid cells.After the combination treatment of NS398 and irradiation,SF2 value of parental cells was lower than spheroid cells(t =2.91,P ＜ 0.05)and the SER of NS398 on parental cells was greater than spheroid cells.The expressions of Bmi-1,c-Myc,β-catenin and Cyclin D1 in spheroid cells were higher than those in parental cells (t =8.09,7.90,7.50,7.15,P＜0.05).Cyclin D1 expression levels under both cell situations increased after 4 Gy irradiation (t =9.74,6.67,P ＜0.05).Compared to the 4 Gy irradiation alone group,the β-catenin and Cyclin D1 expression levels in both parental cells (t =10.15,12.12,P ＜ 0.05) and spheroid cells (t =3.23,7.45,P ＜ 0.05) decreased in the combination group.Conclusions Esophageal cancer stem cells with high level of CD271 can be isolated with serum-free medium and it is radioresistant where β-catenin and its downstream proteins may be involved.

ObjectiveTo investigate prognostic factors in Stage Ⅲ non-small cell lung cancer (NSCLC)treated with definitive radiation therapy (RT) with PET-CT-based radiotherapy planning. MethodsFifty nine patients with Stage Ⅲ NSCLC treated with radiation therapy of 60 Gy or more were enrolled into this study.The impact of prognostic factors on survival was evaluated by univariate and multivariate analyses. Results The following-up rate was 98％.Nineteen patients completed 2 years' followed-up. The overall l-year and 2-year survival rate was 66％ and 37％, respectively, with a median survival time of 17 months. At a univariate analysis, cigarette smoking status, T stage, radiation dose, the standardized uptake value, the gross tumor volume and clinical stage were significant prognostic factors ( x2 =7.46,7. 52,8.37,4. 97,5.82,4. 37, P =0. 006,0. 006,0. 004,0. 026,0. 016,0. 037, respectively ).At multivariate analyses, cigarette smoking status, radiation dose, gross tumor volume and clinical stage were significant prognostic factors ( x2 =6. 20, 9. 69, 6. 39, 10. 09, P =0. 013,0. 002, 0. 011,0. 001,respectively). Conclusions Cigarette smoking status, radiation dose, gross tumor volume and clinical stage are significant prognostic factors on survival in patients with Stage Ⅲ NSCLC treated with RT based on PET-CT radiotherapy planning.

Objective To identify the association of oxygen saturation of arterial hemoglobin (SaO2) with late-onset hypertension in the Chinese Han population located in the Daxinganling area.Methods A total participants were selected by convenience sampling methods from the Daxinganling area.All data were collected from each person by the questionnaire record of physical examinations as well as biochemical index measuring.SaO2 was noninvasively measured with finger pulse oxymetry,the reported SaO2 was the average of three readings taken 10 seconds apart.Results There were significant differences for SaO2 within the population of individuals,the mean SaO2 values was 97.71%±6.14%,with range from 88% to 100%.There was association of SaO2 with sex,BMI and age.SaO2 level declined with BMI and age increasing.Particularly,it was found that the risk increasing to hypertension was marked association with SaO2 rapid drop.During the period from 40-50 years of age,SaO2 declined from 97.85% to 97.64%,The risk to hypertension increased more than 10 times(P<0.001).That implicated hypoxia mightinvolve in the etiology of hypertension.Conclusions The preliminary results demonstrated the rapid decline of SaO2 with lapse of age may be one of the major risk factors to hypertension,it may be helpful to explain late-onset hypertension to some extent at least.

Objective To investigate the effects of Polygonatum kingianum on wound healing and nuclear factor-erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway in diabetic skin injury rats.Methods Diabetic rat models were established and 48 rats were randomly divided into model group,sitagliptin group(10 mg·kg-1),Polygonatum kingianum water extract low dose group(2 g·kg-1),Polygonatum kingianum water extract high dose group(8 g·kg-1)and Polygonatum Kingianum alcohol extract low and high dose group(2 g·kg-1 and 8 g·kg-1).8 in each group;Another control group was set up.After 4 weeks of intragastric administration,all rats established back skin wounds,and continued to be administered for 14 days after operation.At the end of the experiment,the rats were killed,and blood glucose,glycosylated hemoglobin(GHb),plasma levels of H2O2,MDA,SOD,GSH and wound margin skin tissue T-AOC,SOD,MDA levels were measured.The relative expression of Nrf2 and HO-1 mRNA in wound margin skin tissue was measured by fluorescence quantitative method.Results Compared with the model group,the levels of SOD and GSH in plasma and the relative expressions of Nrf2 and HO-1 mRNA in wound margin skin tissue in the low and high dose groups of ethanol extract of Polygonatum kingianum,and the low and high dose groups of water extract of Polygonatum kingianum were increased(P<0.01,P<0.001).The levels of glycosylated hemoglobin(GHb)in plasma and MDA in wound margin tissue were decreased(P<0.05,P<0.01,P<0.001).The level of T-AOC in the high dose group was increased(P<0.01).The SOD level of skin tissue in the low dose group of Polygonatum kingianum water extract was increased(P<0.01),and the level of H2O2 in the low dose group was decreased(P<0.01).Conclusion Polygonatum canaliculatum can up-regulate Nrf2/HO-1 signaling pathway,regulate excessive oxidative stress,and promote wound healing.

Objective To screen predictors for the prognosis of patients with inoperable locally advanced esophageal squamous carcinoma (LAESC) who are undergoing concurrent radiochemotherapy and establish a preliminary scoring system. Methods The data of 75 patients with inoperable LAESC who were undergoing intensity-modulated radiation therapy and concurrent chemotherapy were collected and analyzed to determine whether the prognosis was associated with medical history,vital signs,and the results of routine blood test and liver and kidney functions test before and at the end of radiochemotherapy. The prediction efficacy of the model was assessed using the receiver-operating characteristic curve. The degree of fitting was tested using the Hosmer-Lemeshow goodness-of-fit test. Results Seventy-five patients with LAESC were included. The univariate analysis indicated that the prognosis of the patients with LAESC who were undergoing concurrent radiochemotherapy was associated with weight loss of more than 5％,poor dietary habit,and significant decrease in white blood cell count (P = 0.047,0.074,and 0.074). The multivariate Cox model was conducted,and a scoring system for prediction of prognosis was established. The scores were 1.5 for weight loss of more than 5％,1.0 for poor dietary habit,and 1.0 for a significant decrease in white blood cell count (more than 2.0×109/L). A total score of more than 2.25 indicated a high mortality risk,with a sensitivity of 0.559 and a specificity of 0.805. Conclusion The simple and practical scoring system for prediction of prognosis of patients with LAESC in this study could generally predict the mortality risk of patients with inoperable LAESC who are undergoing concurrent radiochemotherapy.

Objective To evaluate the radiosensitization effect of apatinib on esophageal cancer cell line Kyse-150, and to investigate the underlying mechanism. Methods Cells were divided into four groups:control group, apatinib treatment group, X-ray radiation group, and the combination group treated with X-rays plus apatinib. The effect of apatinib with different concentrations on the cell proliferative and radiosensitivity were evaluated by CCK-8 kit and colony formation assay. Flow cytometry method was adopted to detect the effect of apatinib on cell cycle progress and apoptosis induction. Results Apatinib inhibited the proliferation of Kyse-150 cells in time-and dose-dependent manners (r=0. 89-0. 96, P<0. 05). With the increase of apatinib concentration, D0, Dq and SF2 value of Kyse-150 cells decreased and SERD0 value increased. Compared with control group, apatinib alone group, and radiation alone group, the cell apoptosis rate significantly increased in the combination group (t=12. 36, 5. 99, 15. 47,P<0. 05). Compared with control group, the percentages of cells in G2/M phase were all significantly increased in apatinib group, radiation group and combination group (t=8. 81, 39. 69, 20. 61,P<0. 05). Compared with radiation alone group and control group, the percentage of cells in S phase significantly increased in apatinib alone group and combination group(t = 6.06, 3.82,8.81,6.24,P < 0.05). Conclusions Apatinib can increase radiosensitivity of esophageal cancer cell line Kyse-150 possibly by inhibiting cell proliferation, inducing cell apoptosis and causing redistribution of cell cycle.

Objective To evaluate the radiosensitivity effects of apatinib on the esophageal cancer cell line ECA-109 and its cancer stem-like cells,and to investigate the underlying mechanism.Methods A serum-free medium (SFM) was used to culture esophageal cancer stem cell line ECA-109 and enrich the esophageal stem-like spheres.ECA-109 and its stem-like cells were divided into control group,drug treatment group,radiation group and drug plus radiation group.Cell proliferations of ECA-109 and its stem-like cells were detected with CCK-8 method.The concentration of vascular endothelial growth factor (VEGF) in the cell culture medium was determined by enzyme linked immunosorbent assay(ELISA).Cell cycle and apoptosis were detected by flow cytometry method.The expressions of CHK2 and P-STAT3 proteins were detected by Western blot assay.Results With the administration with apatinib for 24,48 and 72 h,the half of the inhibitory concentration (IC50) of ECA-109 stem-like cells was significantly higher than that of the parent cells (t =8.17,9.29,18.85,P ＜ 0.05) in a time dependent manner (parental cells:r2 =0.94-0.97,P ＜0.05;stem-like cells:r2 =0.94-0.98,P ＜0.05).After administration with different concentrations of apatinib (parental cells:10 and 20 μmol/L;stem-like cells:30 and 40 μmol/L) combined with different dose of X-rays (6 and 8 Gy),the proliferations of ECA-109 and its stem-like cells were significantly (t =5.20-39.68,P ＜ 0.05) inhibited compared with radiation alone group.VEGF secretion from both ECA-109 cells and its stem like cells were significantly decreased in different manner (t =7.45,P ＜ 0.05).Compared with control group,the cell apoptosis rate and the percentages of cells in G2/M phase were significantly increased in drug plus radiation group (t =8.83,11.59,P ＜ 0.05),and the expressions of CHK2 and P-STAT3 were decreased in drug group (t =3.36,4.10,P ＜ 0.05).Compared with radiation group,the expressions of CHK2 and P-STAT3 were decreased in drug plus radiation group (t =9.05,2.36,P ＜ 0.05).Conclusions Apatinib enhanced the radiosensitivity of ECA-109 cells and its stem-like cells,which was much more effective on ECA-109 cells and may be related to the radiation-induced inhibition of VEGF signal pathway that can further inhibit cell proliferation,promote cell apoptosis and induce cell cycle redistribution.The higher intrinsic level of VEGF protein may contribute to radioresistance of ECA-109 stem-like cells.

Ferroptosis is a new programmed cell death dependent on iron ions.Ferroptosis can be induced by endogenous or exogenous pathways, and cells exhibit specific cell morphological signs and are regulated by a variety of molecular mechanisms.In recent years, more and more studies have shown that ferroptosis plays an important role in the treatment of cancer.This article summarizes the mechanism of ferroptosis in bladder cancer and the regulation of cancer cells, as well as the role of ferroptosis-related factors, non-coding RNA regulation, N6-methyladenosine (m6A), amino acid metabolism and autophagy dependent ferroptosis in the growth and proliferation of bladder cancer, with a view to provide new strategies for the treatment of bladder cancer.

Objective: To investigate the in vitro and in vivo effects of apatinib in esophageal squamous cell carcinoma and the underlying mechanisms. Methods: The esophageal cancer cells, KYSE-150 and ECA-109, were divided into control group and apatinib treatment group at the concentrations of 2.5, 5, 10, 20 and 40 μmol/L respectively. All of experiments were performed in triplicate. MTT and colony formation assays were used to measure cell proliferation. Transwell assay was used to determine the migration capacity. The effect of apatinib on cell cycle and apoptosis was analyzed by flow cytometry. The expression of VEGF and VEGFR-2 was measured by real-time quantitative PCR (qRT-PCR). The concentration of VEGF in the cell supernatant was assessed by enzyme-linked immunosorbent assay (ELISA). The expression levels of MEK, ERK, p-MEK, p-ERK, JAK2, STAT3 and p-STAT3 after VEGF stimulation were detected by Western blot. Furthermore, the nude mice xenograft model was established. The tumor-bearing mice were randomly divided into control group, apatinib low dose treatment group (250 mg) and apatinib high dose treatment group (500 mg), respectively. Tumor inhibition rates of different groups were calculated. And then the expressions of VEGF and VEGFR2 were detected in xenograft tissues by immunohistochemical staining. Results: In the presence of 20 μmol/L and 40 μmol/L of apatinib for 24 hours, the migration cell numbers of KYSE-150 and ECA-109 were 428.67±4.16 and 286.67±1.53 as well as 1 123.67±70.00 and 477.33±26.84, respectively, that were significantly lower than control group (P<0.05 for all). In addition, after treatment with 10 μmol/L, 20 μmol/L and 40 μmol/L of apatinib for 7 days on KYSE-150 and ECA-109, the colony formation rates were (65.12±25.48)%, (58.19±24.73)% and (29.10±22.40)% as well as (70.61±15.14)%, (61.12±17.21)% and (43.09±11.13)%, respectively. The colony formation rates of 20 μmol/L and 40 μmol/L of apatinib treatment groups were significantly lower than control group (100.00±0.00, P<0.05). The cell cycle ratio of G₂/M phase and apoptosis rate of control group and 20 μmol/L apatinib group in KYSE-150 cells were (12.14±2.13)% and (3.49±0.74)% as well as (26.27±3.30)% and (15.65±1.54)%, respectively. The corresponding ratios in ECA-109 cells were (3.44±0.57)% and (6.31±1.43)% as well as (22.64±2.36)% and (49.26±1.62)%, respectively. The results show that apatinib suppressed cell cycle progression at G₂/M phase and induced cell apoptosis in both KYSE-150 and ECA-109 cells (P<0.05 for all). In the presence of 20 μmol/L and 40 μmol/L of apatinib in KYSE-150 cells, the relative levels of VEGF mRNA were (42.57±10.43)% and (25.69±1.24)%, and those of VEGF-2 mRNA were (36.09±10.82)% and (13.99±6.54)%, which were all significantly decreased compared to control group (100.00±0.00, P<0.05 for all). For ECA-109 cells, the relative expression of VEGF and VEGFR2 showed similar tendency (P<0.05 for all). Moreover, after treatment with 20 μmol/L and 40 μmol/L of apatinib in KYSE-150 cells, the VEGF concentrations were (766.48±114.27) pg/ml and (497.40±102.18)pg/ml, which were significantly decreased compared to control group [(967.41±57.75) pg/ml, P<0.05)]. The results in ECA-109 were consistent (P<0.05). Furthermore, after treatment with 40 μmol/L of apatinib in KYSE-150 and ECA-109, the relative expression of p-MEK and p-ERK were 0.49±0.05 and 0.28±0.03 as well as 0.63±0.03 and 1.22±0.15, which were significantly lower than control group (1.23±0.19 and 0.66±0.07 as well as 1.03±0.20 and 1.76±0.20; P<0.05). The relative expression of STAT3, p-STAT3 in control group and experimental group were 0.96±0.15 and 0.85±0.16 as well as 0.62±0.09 and 0.36±0.13, respectively. The results showed that the protein levels of STAT3 and p-STAT3 were significantly lower than the control group (P<0.05 for all). The inhibition rates of apatinib in xenograft nude mice were 29.25% and 19.96% for 250 mg and 500 mg treatment groups. The concentration of VEGF were (25.11±4.12) pg/ml, (16.40±2.81) pg/ml and (15.04±4.88)pg/ml for control, 250 mg and 500 mg treatment groups, respectively. Conclusions Apatinib can inhibit cell proliferation, induce apoptosis and suppress migration of esophageal cancer cells in vitro and in vivo. This effect was mainly mediated via the alterations of Ras/Raf/MEK/ERK pathway and JAK2/STAT3 pathway.