Objective: To optimize the formula and preparation technology of cantharidin chitosan bioadhesive microspheres.Methods: The microspheres were prepared by a spray drying method.A single-factor experiment was used to study the effect of chitosan with different molecular weight on the gastric mucosa adhesion rate were also studied, and the effects of different drug loading ratio, concentration of chitosan acetic acid solution and speed of peristaltic pump on the loading rate were also studied.The cantharidin entrapment efficiency as the studying index, a response surface method was used to further optimize the formula.Results: The best formula and preparation process of cantharidin chitosan bioadhesive microspheres were as follows: the concentration ratio of antharidin to chitosan was 19.83% , the concentration of chitosan acetic acid solution was 0.77% , and the peristaltic pump flow rate was 9.225 ml·min-1.With the best formula, the entrapment efficiency of cantharidin chitosan bioadhesive microspheres was 90.14%.Conclusion: The microsphere preparation by the spray drying method is stable and repeatable.Cantharidin chitosan bioadhesive microspheres have high entrapment efficiency and promising biological adhesion.

Objective To investigate the imaging characteristics of mucinous tubular and spindle cell carcinoma of the kindey (MTSCC-K).Methods Five cases of pathologically confirmed MTSCC-K were analyzed retrospectively.All patients underwent CT scanning,and 4 cases underwent conventional MR and diffusion weighted imaging (DWI) scanning.MR enhancement ratio for the tumor was calculated according to MR signal intensity of pre-and post-contrast in tumor and apparent diffusion coefficient (ADC) values of tumor and normal renal cortical.Results Two case located in the right kindey,and 3 cases located in the left kindey.The maximum diameter of lesions ranged from 3.2 cm to 7.1 cm.Five cases showed nearly round shape with clear borderline.Pseudocapsule was found in 4 cases,3 cases had necrosis and cystic,and 1 case had calcification.There were no hemorrhage,fat and invasion of adjacent tissue.Isodensity or hypodense tumors were found on plain CT.Isointense or hyperintense tumors were found on plain T1WI,while isointense or mixed-signal tumors were found on plain T2WI.Slightly homogeneous or heterogeneous enhancement was observed on dynamic enhanced CT or MR,and the solid component of tumors showed hyperintense on DWI and hypointense on ADC.The mean CT value of tumor at the plain,cortical and nephrographic phase was 32.6 HU,46.5 HU and 66.5 HU,respectively.The mean ADC value of tumor and normal renal cortical was 1.23 × 10-3 mm2/s and 2.31 × 10-3 mm2/s,respectively.The mean MR percentage of enhancement value of tumor was 32.7％ and 104.9％,respectively.Conclusions The imaging characteristics of MTSCC-K include nearly round shape,pseudocapsule,clear borderline,necrosis,cystic and calcification.There is no invasion of adjacent tissue and seldom malignant appearances.Isodensity or hypodense can be observed on plain CT,isointense or hyperintense on plain T1WI,and a mild continuously enhancement on dynamic enhanced scanning.

Objective Enzyme triggered multi unit colon targeting mini tablet of indomethacin were prepared,in order to improve the target treatment of colon disease.Methods Different proportion of enteric layer and chitosan layer were screened to optimize the prescription.The colon targeting mini tablets were prepared by direct compression method.The drug release properties were investigated in different release medium.Rats were used to investigate the distribution of tissue in vivo.The Beagle dogs were used to study the pharmacokinetics and bioavailability.Results The optimum chitosan layer prescription:coating liquid concentration was 2％,plasticizer three citric acid ethyl ester (TEC) was 15％,an anti sticking agent amount of talc was 30％,coating weight was 5％;Enteric layer prescription:coating liquid solid content was 20％,plasticizer content of TEC was 5％,anti sticking agent talc powder dosage was 40％,coating weight was 3％.The chitosan multi unit colon targeted preparation seldom released in rat stomach and small intestine,released slowly in colon.The pharmacokinetics parameters in Beagle dogs were:Cmax =(3.25 + 0.672) mg·L-1,tmax =(2.00 + 0.014) h,AUC(0.∞) =(10.2 +0.871) mg·L-1 ·h,MRT (0-∞) =(2.82 + 0.180) h,CL =(2.46 + 0.202) L·h-1 ·kg-1.The release time of mini tablets for colon targeted was significantly prolonged and preserved stable blood concentration.Conclusion The enzyme triggered multi unit colon targeting mini tablet of indomethacin showed good target to colon and sustained release effect,providing an important reference for the development of preparation of indomethacin for the treatment of colon disease.

Objective To investigate the pathological manifestations of acute?stage radioactive myocardial damage and related mechanisms using an experimental animal model. Methods A total of 12 adult male Sprague?Dawley rats were randomly divided into control group and radiation group. In the radiation group, the model of radiation?induced myocardial damage was established by the irradiation of the anterior myocardial territory with 6?MV X?ray at a single dose of 20 Gy, and at 14 days after irradiation, HE staining was used to observe the morphological changes of cardiomyocytes and intercellular matrix, and Masson staining was used to observe the distribution of collagen fibers. The collagen volume fraction ( CVF) was used for semi?quantitative analysis. ELISA was used to measure the activity of total superoxide dismutase ( T?SOD) and the concentration of malondialdehyde ( MDA ) , and Western blot was used to measure the expression of the fibrosis marker protein collagen type I ( COL?1 ) and the endoplasmic reticulum stress?related proteins GRP78 and CHOP. The t?test, t ’?test, or nonparametric rank sum test was used for comparison between groups. Results At 14 days after local irradiation of the heart, the radiation group had disordered arrangement of cardiomyocytes, marked edema, rupture of some cardiomyocytes, mild karyopyknosis in cardiomyocytes, and infiltration of inflammatory cells in the myocardial interstitium, compared with the control group. Collagen fibers in the myocardial tissue were mainly distributed in the perivascular area and cardiomyocyte interstitium. The radiation group had a significantly higher CVF than the control group ( 11?35% vs. 5?23%, P=0?000 ) and a significant increase in the expression of COL?1 compared with the control group ( P=0?000) . The radiation group had significant increases in the activity of T?SOD and the concentration of MDA in the myocardial tissue compared with the control group ( T?SOD:156?61 U/mgprot vs. 137?06 U/mgprot, P= 0?042;MDA:2?36 nmol/mgprot vs. 1?31 U/mgprot, P=0?007) . Compared with the control group, the radiation group showed significant increases in the expression of endoplasmic reticulum stress?related proteins GRP 7 8 and CHOP ( P= 0?037 and 0?009 ) . Conclusions The pathological manifestations of acute?stage myocardial damage include degeneration of cardiomyocytes, inflammatory exudation in the interstitium, and deposition of collagen in the perivascular area and myocardial interstitium. Myocardial fibrosis can be observed in the acute stage of radiation?induced myocardial damage, and the mechanism may be related to oxidative stress and endoplasmic reticulum stress induced by radioactive rays.

Objective To evaluate the correlation of ADC values on 3.0 T MR with the pathological grades in pT1b clear cell renal cell carcinoma(CCRCC).Methods Conventional MR images,ADC values and Fuhrman pathological grading of pT1b CCRCC were performed in 30 patients.Grade Ⅰ and Ⅱ were defined as low-grade group; grade Ⅲ and IV were defined as high-grade group.The differences of ADC values among four different pathologic grades were compared with a one-way analysis of variance. The comparison of ADC values of two different grade groups was performed with t test,and the ROC curve was performed to evaluate the diagnostic efficacy of ADC value. Correlation between pathological gradings and ADC values was assessed with Spearman rank correlation analysis. Results ( 1 ) The mean ADC value of grading Ⅰ ( 10 patients ), Ⅱ ( 8 patients ),Ⅲ ( 7 patients ),IV ( 5 patients ) was ( 0.94 ± 0.11 ) ×10-3 mm2/s,(0.82 ±0.13) × 10-3 mm2/s,(0.68 ±0.09) × 10-3 mm2/s,(0.59 ±0.03) × 10-3 mm2/s,respectively.Significant differences of ADC values among the four grades were present (F =16.422,P =0.000 ).( 2 ) The mean ADC value of the low-grade group was significantly higher than that of the high-grade group(t =5.738,P =0.000).Sensitivity and specificity of diagnosing the low-grade group was 88.9％ and 83.3％ respectively.There was a negative correlation between pathological grading and ADC value ( r =-0.807,P ＜ 0.05). Conclusions The ADC values of pT1b CCRCC have close correlation with pathological gradings.They can be used to predict the degree of tumor malignancy preoperatively and guide surgical planning.

Objective To investigate the clinical effect of induction chemotherapy plus concurrent radiochemotherapy in the treatment of locally advanced non-small cell lung cancer (NSCLC) through a meta-analysis.Methods CBM, CNKI, Cochrane Library, PubMed, and EMbase were searched for the articles on comparison between induction chemotherapy plus concurrent radiochemotherapy and concurrent radiochemotherapy for patients with locally advanced NSCLC.According to the inclusion and exclusion criteria, the data on short-term outcome and survival were collected.A Meta-analysis was performed to evaluate the clinical effect of induction chemotherapy followed by concurrent radiochemotherapy.Results A total of 5 articles were included, which involved 845 patients.The results showed that the short-term outcome and the 2-and 3-year survival rates were similar between patients receiving induction chemotherapy plus concurrent radiochemotherapy and those receiving concurrent radiochemotherapy ( OR=0.875, 95% CI 0.507-1.510, P=0.631;HR=0.770, 95% CI 0.515-1.151, P=0.203;HR=0.809, 95% CI 0.559-1.172, P=0.262), but the patients receiving induction chemotherapy plus concurrent radiochemotherapy showed a significantly higher incidence rate of grade ≥ 3 leukopenia than those receiving concurrent radiochemotherapy alone ( OR=0.637, 95% CI 0.435-0.931, P=0.020).Conclusions Induction chemotherapy plus concurrent radiochemotherapy shows no significant advantages over concurrent radiochemotherapy alone in the short-term outcome and 2-and 3-year survival rates, but it significantly increases myelosuppression.Since there are few studies involving a limited number of cases included in this analysis, more multicenter randomized trials are needed to provide more detailed data and further clarify the clinical value of induction chemotherapy plus concurrent radiochemotherapy.

Objective To examine the effects of different pre-treatment nutritional status and inflammatory markers on acute adverse reactions in esophageal cancer patients during concurrent intensity-modulated radiation therapy (IMRT) and chemotherapy.Methods The acute adverse reactions of 338 eligible esophageal cancer patients who received concurrent IMRT and chemotherapy in our hospital from 2006 to 2014 were reviewed.The effects of different pre-treatment nutritional status, such as body mass index level (BMI), albumin level (ALB), total lymphocyte count (TLC), the presence or absence of anemia, and inflammatory indicators including neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR), on acute adverse reactions in the patients were examined.Data were analyzed using the chi-square test with continuity correction and logistic regression analysis.Results The incidence rate of malnutrition in the patients based on their nutritional status was 5.62%-54.14%.The incidence rate of grade≥2 acute radiation esophagitis (RE) was significantly higher in the low ALB group than in the normal ALB group (P=0.000).The incidence rate of adverse reactions in the hematologic system increased as TLC decreased (P=0.006), but the incidence rate of acute radiation pneumonitis (RP) was reduced as TLC decreased (P=0.001).In addition, the incidence rate of grade ≥2 acute RE was significantly higher in the anemia group than in the non-anemia group.Inflammatory marker analysis demonstrated that the incidence rate of acute RE was significantly higher in the high NLR group and high PLR group than in the low NLR group and low PLR group (P=0.000 and P=0.024, respectively).Logistic regression analysis of nutritional status and inflammatory markers showed that TLC was an independent risk factor for acute adverse reactions in the hematologic system (P=0.001), and ALB and PLR were independent risk factors for acute RE (P=0.017 and P=0.011,respectively).Conclusions Nutritional status and inflammatory markers are associated with concurrent chemoradiotherapy-induced acute adverse reactions in esophageal carcinoma patients, and hence may be valuable indicators of acute adverse reactions during treatment.In addition, nutritional treatment and support care should be actively provided to the patients to prevent the development of acute adverse reactions during treatment.

Objective To investigate the effect of docosahexaenoic acid (DHA) combined with cyclooxygenase-2 (COX-2) selective inhibitor NS-398 on the apoptosis of cholangiocarcinoma QBC939 cells and the mechanism.Methods In vitro,cholangiocarcinoma QBC939 cells were treated with 0,15,30,45,60 and 75 μg/ml DHA with 0,25,50,100,150 and 200 μmol/L NS-398,respectively.The absorbances of the QBC939 cells were measured by CCK8 and its growth inhibition ratios were analyzed.Flow cytometry was applied to detect cell apoptosis.The level of β-catenin and COX-2 mRNA and protein were measured by real-time PCR,immunocytochemistry and enzyme-linked immunoadsordent assay,respectively.Results DHA combined with NS-398 could significantly suppress the growth of QBC939 cells (P ＜ 0.05).When the concentration of DHA went up to 45 μg/ml and NS-398 was 100 μmol/L,the relative growth inhibition rate of QBC939 cells was 90.0％.If the concentrations were increased,the result showed no significant differences.Furthermore,flow cytometry analysis indicated that DHA combined with NS-398 could induce QBC939 cells apoptosis at the early stage,and the apoptosis rate was significantly different between the experimental and control groups (P ＜ 0.01).Real-time PCR showed low β-catenin and COX-2 expression in QBC939 cells disposed by DHA combined with NS-398,and their expression were significantly different between the experimental and control groups (P ＜ 0.01).Immunocytochemistry and ELISA demonstrated that DHA combined with NS-398 could decrease β-catenin and COX-2 protein expression in QBC939 cells.Conclusion DHA combined with NS-398 induced apoptosis and inhibited proliferation of cholangiocarcinoma cells QBC939 in vitro through targeting β-catenin and COX-2.

postoperative pathological examination results and radiotherapy toxicities. Results All the 45 patients completed preoperative concurrent chemoradiotherapy and surgery, with two cycles of chemotherapy in 39 patients and one cycle in 6 patients. The rates of R0resection and pathological complete response(pCR) were 95.6%(43/45)and 22.2%(10/45), respectively. There were 10(22.2%), 17(37.8%), 15 (33.3%),and 3(6.7%)patients with tumor regression grades 0,1,2,3,respectively. The rate of lymph node metastasis was 37.8%(17/45),and the lymph node ratio was 4.33%(46/1 062). The postoperative pathological examination showed that T and N downstaging after surgery was observed in 24 and 26 patients, respectively;the proportions of patients with T3-T4tumors and positive lymph nodes after surgery declined by 51.1%(P=0.000)and 42.2%(P=0.000), respectively. The overall incidence of radiation esophagitis/gastritis was 44.4%(20/45), and the incidence rates of grade 1, 2, and 3 radiation esophagitis/gastritis were 18%,22%,and 4%,respectively. The incidence of acute radiation pneumonitis was 6.7%(3/45), all in grades 1 and 2. There was one perioperative treatment-related death. Conclusions Two cycles of XELOX chemotherapy combined with concurrent 45 Gy radiotherapy before surgery in patients with locally advanced Siewert type Ⅱ and Ⅲ AEG can achieve a relatively high pCR rate,effectively reduce the lymph node metastasis rate, achieve downstaging, and increase R0resection rate. This regimen has many good advantages,including low incidence of acute toxicities,good tolerability,and acceptable rate of perioperative treatment-related deaths. The target volume delineation involving metastatic lymph nodes is feasible.

OBJECTIVETo explore the expression of hypoxia inducible factor-1α(HIF-1α) in esophageal squamous cell carcinoma and its correlation with clinicopathological features.

METHODSOriginal literatures in foreign languages regarding correlation between HIF-1α and esophageal squamous cell carcinoma were identified from Cochrane Library, PubMed, EMbase database, and Chinese original literatures were from CBM, CNKI. All analyses were performed by Stata 11.0 software. Histological grade, degree of differentiation, T stage, lymph node metastasis, tumor stage, lymphatic invasion and vascular invasion were analyzed using pooled odds ratio (OR) with 95% confidence interval (CI).

RESULTSA total of 14 studies including 1 121 patients were enrolled in this meta analysis. Comparing with normal tissue, the expression of HIF-1α in esophageal squamous cell carcinoma was significantly enhanced (OR = 0.088, 95% CI: 0.061-0.129, P = 0.000); HIF-1α was significantly associated with T stage and lymph node metastasis (OR = 0.421, 95% CI: 0.222-0.798, P = 0.008; OR = 0.387, 95% CI: 0.207-0.725, P = 0.003). High expression of HIF-1α was correlated with an increased depth of tumor invasion, more lymph node metastasis and advanced tumor stage, whereas there was no relation to the degree of differentiation, histological grade, tumor stage, lymphatic invasion and vascular invasion.

CONCLUSIONSHigh expression of HIF-1α protein correlates with an increased risk of esophageal squamous cell carcinoma. HIF-1α may be an indicator for T stage, lymph node metastasis and tumor stage, but further studies are needed.

Biomarkers, Tumor ; metabolism ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Confidence Intervals ; Esophageal Neoplasms ; metabolism ; pathology ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Lymphatic Metastasis ; Odds Ratio