Objective To analyze the correlation between morphological and dosimetric parameters in patients with esophageal cancer at different locations using multi-to-multi double screening stepwise regression method,and to make simple predictions.Methods A retrospective analysis was conducted on 105 patients with advanced esophageal cancer who underwent radiotherapy at the First Affiliated Hospital of Fujian Medical University from 2019 to 2021.Morphological parameters of organs-at-risk were collected from CT images,and intensity-modulated radiotherapy plans were developed using Raystation4.7.The prescription doses for PTV-G and PTV-C were 60 Gy/30 F and 54 Gy/30 F,respectively.Multi-to-multi double screening stepwise regression method was employed to analyze the correlation between morphological and dosimetric parameters in esophageal cancer patients,and some preliminary predictions were provided.Results The dosimetric volume parameters of the lungs and heart were correlated with PTV-G volume,PTV-G length,PTV-G cross-sectional area,left and right lung volumes,lung length and total lung volume(P<0.05).For upper thoracic esophageal cancer,dosimetric volume parameters of the lungs and heart were correlated with PTV-G volume,PTV-G length,and right lung volume(P<0.05).For middle thoracic esophageal cancer,dosimetric volume parameters of the lungs,heart,and spinal cord were correlated with PTV-G volume,PTV-G length,PTV-G cross-sectional area,left and right lung volumes,and lung length(P<0.05).For lower thoracic esophageal cancer,dosimetric volume parameters of the lungs,heart,and spinal cord were correlated with PTV-G volume,PTV-G length,right lung volume,and lung length(P<0.05).Conclusion For patients with tumors at different locations,both overall and segmental analyses should be considered to balance therapeutic effect and side effects of radiotherapy,thereby maximizing the benefits for tumor patients.

Objective To analyze the correlation between morphological and dosimetric parameters in patients with esophageal cancer at different locations using multi-to-multi double screening stepwise regression method,and to make simple predictions.Methods A retrospective analysis was conducted on 105 patients with advanced esophageal cancer who underwent radiotherapy at the First Affiliated Hospital of Fujian Medical University from 2019 to 2021.Morphological parameters of organs-at-risk were collected from CT images,and intensity-modulated radiotherapy plans were developed using Raystation4.7.The prescription doses for PTV-G and PTV-C were 60 Gy/30 F and 54 Gy/30 F,respectively.Multi-to-multi double screening stepwise regression method was employed to analyze the correlation between morphological and dosimetric parameters in esophageal cancer patients,and some preliminary predictions were provided.Results The dosimetric volume parameters of the lungs and heart were correlated with PTV-G volume,PTV-G length,PTV-G cross-sectional area,left and right lung volumes,lung length and total lung volume(P<0.05).For upper thoracic esophageal cancer,dosimetric volume parameters of the lungs and heart were correlated with PTV-G volume,PTV-G length,and right lung volume(P<0.05).For middle thoracic esophageal cancer,dosimetric volume parameters of the lungs,heart,and spinal cord were correlated with PTV-G volume,PTV-G length,PTV-G cross-sectional area,left and right lung volumes,and lung length(P<0.05).For lower thoracic esophageal cancer,dosimetric volume parameters of the lungs,heart,and spinal cord were correlated with PTV-G volume,PTV-G length,right lung volume,and lung length(P<0.05).Conclusion For patients with tumors at different locations,both overall and segmental analyses should be considered to balance therapeutic effect and side effects of radiotherapy,thereby maximizing the benefits for tumor patients.

Objective To examine the effects of p38 mitogen-activated protein kinase (MAPK) inhibitor on the behavioral response to zebrafish larvae after hypoxia/reoxygenation brain injury and to identify whether the protective effect is mediated by inhibiting apoptosis and protein,and mRNA related to apoptosis.Methods The 5-day post-fertilization zebrafish larvae were randomly assigned to 3 groups:control group,model group and intervention group.Fishes in the intervention group were separated into 3 subgroups according to p38 MAPK inhibitor concentration (5,10,20 μmol/L).The activity levels of the larvae were analyzed by using quantization mode of ZebraLab software,swimming distance and moving speed were recorded.Terminal transferase dUTP nick end labeling (TUNEL) assays of brain assays were performed.The protein levels of phosphorylation of p38 MAPK,apoptosis related proteins of B-cell lymphoma-2 (Bcl-2),Bcl-2 associated X protein(Bax) and Caspase-3 were determined by Western blot.The mRNA expressions of Bcl-2,Bax,and caspase-3 were also analyzed by reverse transcription-quantitative PCR (RT-qPCR).Results The activity movement analysis of the intervention group 2 and 3 demonstrated a significantly increase in the swimming distance compared with the model group(P ＜ 0.05).After irradiation under strong light,all groups showed dramatically increasing in the moving speed.After removal of strong light,a significant decrease in moving speed was found in the control group and intervention group 2 and intervention group 3.The TUNEL assay showed that apoptosis index decreased in the intervention group (21.7 ±2.0,12.8 ± 1.9,17.7 ±2.6) compared with model group (46.8 ±5.3) (all P ＜0.01).Western blot assays demonstrated a significant increase protein level of phosphorylation of p38 MAPK after hypoxia and reoxygenation,and the inhibitor reduced the p-p38 MAPK expression.Compared with the model group,p38 MAPK inhibitor increased the protein and mRNA expression level of Bcl-2,whereas reduced the Bax and caspase-3 expression in the brain.Conclusions Under the influences of p38 MAPK inhibitor,zebrafish larvae improved the behavioral changes after hypoxia-induced brain injury.The inhibitor (10 μmol/L) optimally reduces hypoxia-induced apoptosis in brain by up-regulating Bcl-2,down-regulating Bax/caspase-3 protein and their mRNA level.

Background Reasearches showed that α-melanocyte-stimulating hormone (α-MSH) inhibits inflammation and ameliorates the ocular surface abnormalities in a scopolamine-induced dry eye rat model,and the managing effect of sodium carboxymethylcellulose (CMC) on dry eyes also has been determined.However,whether α-MSH can enhance the therapeutic effects of CMC remains to be investigated.Objective This study was to investigate the protective effects of α-MSH combined with CMC on ocular surface in a scopolamine-induced dry eye rat model.Methods Sixty clean female Wistar rats were randomly divided into normal control group,model control group,NaCl group,CMC group,α-MSH group and α-MSH+CMC group,and 10 rats for each group.The dry eye models were established by subcutaneous injection of scopolamine hydrobromide at 9:00,12:00,15:00 and 18:00 per day for 28 days.0.9％ NaCl solution,1×10 3 mg/ml α-MSH solution,0.5％ CMC eye drop,and 1 ×10-3 mg/ml α-MSH+0.5％ CMC solution were topically administered twice a day (8:00,17:00) since the initial day of modeling according to grouping.Shirmer Ⅰ test (S Ⅰ t),breakup time of tear film (BUT) and corneal fluorescence staining were performed before and 7,14,21,28 days after the application of drugs.At 28 days following the administration of drugs,the eyeballs of the rats were collected.Hemotoxylin and eosin staining was employed to examine the morphology of corneas,and periodic acid schiff (PAS) staining was used to count the conjunctival goblet cells.This study protocol was approved by Experimental Animal Ethic Committee of Tianjin Medical University (SYXK 2009-0001),and the use and care of the rats complied with ARVO Statement.Results The S Ⅰ t and BUT values were significantly reduced,and the corneal fluorescence staining scores were significantly increased over time following modeling in the model control group (all at P＜0.01).No significant differences were found in the S Ⅰ t,BUT and corneal fluorescence staining scores between model control group and NaCl group at various time points (all at P＞0.05).At 7,14 and 21 days after intervention,the S Ⅰ t values were (4.800±0.789),(4.100±0.516) and (4.300±0.856) mm in the α-MSH+CMC group,which were considerably higher than (2.875 ±0.719),(2.375 ±0.619) and (2.532±0.957)mm in the NaCl group (all at P＜0.01).At 7 days after intervention,the BUT values were (4.938± 1.843) seconds and (5.000±1.491) seconds in the α-MSH group and α-MSH+CMC group,which were significantly higher than (3.250±1.000) seconds in the NaCl group (both at P＜0.01).The corneal fluorescence staining scores in the CMC group,α-MSH group and α-MSH+CMC group were significantly lower than that in the NaCl group,with the lowest score in the α-MSH +CMC group (all at P＜0.05).The thickening of corneal epithelial layer,corneal edema and arrangement disorder of corneal stroma were found in the model control group and NaCl group;while slight corneal edema and epithelial cell proliferation were exhibited in the α-MSH+CMC group by hemotoxylin and eosin staining.PAS staining showed that the number of goblet cells was much more in the CMC group,α-MSH group and α-MSH+ CMC group than that in the model control group and NaCl group (all at P ＜ 0.01).Conclusions The sole application of α-MSH or CMC alleviates ocular surface damage and morphological abnormality to certain extent,and the combination of α-MSH and CMC generates more effective protection in comparison with sole administration of α-MSH or CMC.The early application of the drugs plays an improvement role in tear secretion and tear film stability in dry eyes.

Objective To investigate the expression of endoplasmic reticulum stress - related factors, glucose - regulated protein 78(GRP78)and growth arrest and DNA damage - inducible protein 34( GADD34)and neuronal apoptosis in the brain of zebrafish larvae after hypoxia/ reoxygenation brain injury,and the neuroprotective role of Taurine. Methods The 5 day post - fertilization zebrafish larvae were randomly assigned to 3 groups:control group, hypoxia/ reoxygenation model group(model group)and Taurine treatment group(Taurine group). According to the dif-ferent time points for observation,each group was subdivided into 5 subgroups(1 h,3 h,6 h,24 h,48 h)with 100 ze-brafish larvae each. The pathological changes in the brain tissues and cell apoptosis were detected by fluorescence ter-minal deoxynucleotidyltransferase - mediated dUTP nick end - labeling( TUNEL). The expression of GRP78 and GADD34 mRNA in the brain of zebrafish larvae were detected by real - time quantitative reverse transcription PCR (qRT - PCR). The changes in GRP78 and GADD34 protein were detected by Western blot. Results (1)TUNEL:apoptosis index(AI)was increased after hypoxia/ reoxygenation,and reached the peak at 3 h in model group,the AI in Taurine group was decreased compared with that in the model group at the same time point(1 h:22. 83 ± 1. 80 vs 30. 18 ± 1. 81,3 h:23. 22 ± 2. 46 vs 42. 97 ± 4. 01,6 h:16. 80 ± 1. 69 vs 22. 97 ± 1. 91,all P ﹤ 0. 05).(2)qRT -PCR:the expression of GRP78 and GADD34 mRNA was increased at 1 h after hypoxia/ reoxygenation,and reached the peak at 3 h in the model group,the expression in Taurine group was decreased compared with that in the model group at the same time point(GRP78 mRNA:1 h:2. 35 ± 0. 13 vs 5. 36 ± 0. 35,3 h:3. 08 ± 0. 33 vs 4. 27 ± 0. 52,6 h:1. 57 ± 0. 12 vs 3. 00 ± 0. 13,all P ﹤ 0. 05;GADD34 mRNA:1 h:5. 14 ± 0. 55 vs 7. 45 ± 0. 67,3 h:2. 79 ± 0. 58 vs 5. 83 ± 0. 51,6 h:1. 79 ± 0. 22 vs 3. 67 ± 0. 30,all P ﹤ 0. 05).(3)Western blot:the expression of GRP78 and GADD34 pro-tein was increased at 1 h,reached the peak at 6 h,but it was decreased in Taurine group(GRP78 protein:1 h:1. 12 ± 0. 11 vs 1. 37 ± 0. 13,3 h:0. 79 ± 0. 11 vs 1. 25 ± 0. 10,6 h:0. 55 ± 0. 10 vs 1. 52 ± 0. 14,all P ﹤ 0. 05;GADD34 pro-tein:1 h:0. 92 ± 0. 11 vs 1. 11 ± 0. 13,3 h:0. 96 ± 0. 11 vs 1. 52 ± 0. 09,6 h:0. 76 ± 0. 05 vs 1. 89 ± 0. 06,all P ﹤0. 05).(4)The expression of GRP78 and GADD34 protein was positively correlated with AI in the model group(r =0. 53,0. 56 respectively,all P ﹤ 0. 05). Conclusion One of neuroprotective mechanisms of Taurine against hypoxia/reoxygenation brain injury may down - regulate GRP78 and GADD34 expression.

Objective To explore the effect of docosahexaenoic acid (DHA) on long-term learning and memory disorders and potential mechanism in rats after hypoxic ischemic brain damage. Methods Sixty neonatal 7-day-old SD rats were ramdonly divided into three groups: group S (sham operation+vehicle treatment), group C (hypoxic-ischemic brain damage [HIBD]+vehicle treatment) and group D (HIBD+DHA treatment). After left common carotid artery was isolated and ligated for 2.5 h, rats of group C and group D were put into a condition which oxygen concentration was about 8%for 2 h;rats in the group S were only isolated the left carotid artery, without ligation or hypoxia treatment;rats in the group D were intraperitoneally injected DHA of 15 mg/kg after modeling, and rats in the group S and group C were intraperitoneally injected equivalent volume of vehcle, once a day for 10 consecutive days. The pathomorphology changes of the hypocampal CA1 area, and marginal division of striatum were observed by Nissl staining 48 h after modling; the apoptosis cells were measured by TUNEL;immunohistochemical method was used to detect the expressions of Bax and Caspase-3 positive cells in the two brain areas. Morris water maza test was used to evaluate the long-term lerning and momory functions of 2-month-old rats, and the expressions of N-methyl-D-aspartate receptor 1 (NMDAR1) positive cells were detected by immunohistochemical method. Results The pathomorphology damage was significantly improved, the expressions of Bax and Caspase-3 positive cells and the neuron apoptosis in hypocampal CA1 areas and marginal division of striatum in group D were all signficantly decreased as compared with those in the group C (P<0.05). Rats in group D had significantly decreased escape latency as compared with those in group C in Morris water maze test (P<0.05), and the expression of NMDAR1 positive cells in the two brain areas of group D was significantly increased as compared with that in the group C (P<0.05). Conclusion DHA has the ameliorative effect on long-term learning and memory disorders after hypoxic ischemic brain damage in rats, which may be associated with inhibitory action of cell apoptosis at early phase and up-regulation of expression of NMDA1 at the late phase.