Objective To prepare the chitosan nanoparticles loading 5-[125Ⅰ] Iodo-2'-deoxyuridine (125Ⅰ-UdR-CS-DLN) at 100-200 nm in diameter, and analyze the characteristic of drug sustained-releasing and tumor targeting. Methods Orthogonal experimental design and One-way analysis were applied to optimize the preparation of 125Ⅰ-UdR-CS-DLN using tripolyphosphate cross-linking. Dynamic dialysis was utilized to investigate the in vitro releasing characteristics of the nanoparticles. The tumor targeting effect of the nanoparticles was observed with laser confocal microscopy. Results The optimal conditions for preparing the nanoparticles at particle diameters (70. 39 ± 5.12 ) nm (PDI 0. 16 ± 0. 012 ) were 1 g/L of CS, 2 g/L of TPP, stirring rate 600 r/min, relative molecular mass of CS 3 × 103. The TEM results showed that the exterior of the nanoparticles was spheroid, with a uniform and fine dispersivity. The optimized condition with the initial 125Ⅰ-UdR concentration of 2. 96 MBq/ml at pH5 provided the highest loading capacity (1253. 55 MBq/g) and the highest entrapment rate (42. 35% ). The in vitro releasing curves of 125Ⅰ-UdR-CS-DLN followed Higuchi equation, shown a characteristic of long-acting preparation.Laser confocal microscopy observations approved that the tumor cells uptake of FITC-CS-nanoparticles were significantly more than that of normal cells. Conclusions Chitosan nanoparticles loading 125Ⅰ-UdR at diameters range 127. 81 ± 15. 25 nm (PDI 0. 240 ± 0. 035 ) were successfully prepared with the optimized conditions, and showed a characteristic of sustained-releasing and tumor targeting. The chitosan-based nanotechnology provided a new and efficient approach for the application of 125Ⅰ-UdR in intracellular radiotherapy for tumor.

Objective To evaluate the internal irradiation biological effects of 125I-UdR chitosan nanoparticles in hepatoma cells.Methods The accumulation and distribution of 125I-UdR-CS-DLN in hepatoma cells HepG2 and human liver tissue cells HL-7702 were observed with a confocal microscopy.The internal irradiation biological effects were evaluated by MTT assay,flow cytometry and single cell gel electrophoresis.The apoptosis of in situ rabbit liver tumor treated with 125I-UdR-CS-DLN was assayed by TUNEL staining technique.Results After 30 min of nano-particle treatment,its accumulation in the cytoplasm of HepG2 cells was significantly greater than that in HL-7702 cells.When the concentrations of 125I-UdR-CS-DLN was higher than 37 kBq/ml,the cell viability of HepG2 was significantly lower than that of lL-7702 at 24 and 48 h post-treatment(t =-4.46-6.31,P＜0.05),and the HepG2 cells were arrested at G1 phase and significantly impaired at G2/M phase.In addition,the degrees of DNA doublestrand break of both cell lines irradiated by 125I-UdR-CS-DLN were significantly higher than those treated with 125I-UdR,and the DNA repair capacity of HepG2 cells was significantly lower than that of HL-7702 cells(OTM:t =2.94,P ＜0.05;TDNA％:t =10.64,P ＜0.01).TUNEL staining showed that cell apoptosis could be induced in the rabbit liver carcinoma by 125I-UdR-CS-DLN but not by 125I-UdR.Conclusions The amount of 125I-UdR-CS-DLN absorbed by hepatoma cells is significantly higher than that of 125I-UdR,which suggests that 125 I-UdR-CS-DLN induces more stronger internal radiation biological effects of apoptosis and DNA damage on hepatoma cells.

Objective To assess the prognostic benefits of intraoperative radiotherapy (IORT) with electron beam among patients with unresectable locally advanced pancreatic cancer.Methods Between January 2009 and December 2014,167 patients with unresectable locally advanced pancreatic cancer received IORT with electron beam (10-20 Gy) in our hospital.After surgery,12 patients were treated with external beam radiotherapy,56 patients with chemoradiotherapy (CRT),and 17 patients with chemotherapy.Overall survival (OS),local recurrence,and toxicities were retrospectively analyzed.The Kaplan-Meier method was used to calculate survival rates,the log-rank test was used for survival difference analysis and univariate prognostic analysis,and the Cox model was used for multivariate prognostic analysis.Results The follow-up rate was 100％.The median OS time was 10.3 months,and the 2-year OS rate was 22％.The median progression-fiee survival (PFS) time was 6.3 months,and the 2-year PFS rate was 9.9％.The cancer-specific survival (CSS) time was 11.2 months,and the 2-year CSS rate was 23.6％.In the patients treated with IORT alone at doses of＜15 Gy,15 Gy and＞15 Gy,the median OS times were 6.2 months vs.9.1 months vs.22.2 months,and the 1-year OS rates were 10.0％ vs.39.6％ vs.74.4％ (P=0.000).Among the patients receiving postoperative adjuvant therapy,those treated with IORT+CRT had the best survival,with a median OS time of 11.6 months (P=0.033).The univariate analysis showed that IORT dose (P =0.000),tumor size (P =0.006),and IORT applicator diameter (P =0.007) were prognostic factors.The multivariate analysis showed that IORT dose (P=0.000) and IORT combined with CRT (P=0.006) were independent prognostic factors.Conclusions IORT with electron beam is an effective and safe treatment strategy for unresectable locally advanced pancreatic cancer.After protecting surrounding organs,increasing the IORT dose can improve the survival.IORT combined with CRT should be recommended because it improves survival for unresectable locally advanced pancreatic cancer without increasing toxicities.

Objective To study the comparability of total prostate specific antigen ( tPSA) meas-urement by four domestic chemiluminescence immunoassays ( DCI) and electrochemiluminescence immuno-assay ( ECI) . Methods A total of 45 serum samples that requested tPSA tests were selected. Four DCIs ( Snibe MAGLUMI 4000, Mindray CL-2000i, Autobio A2000, HYBIOME AE180) and ECI ( Roche Cobas e601) were used to measure tPSA. The precisions of the methods were evaluated. The four DCIs were com-pared with Roche ECI respectively, and the comparability of the test results was analyzed. Wilcoxon signed rank test and Spearman correlation analysis were used to analyze the data. Results The precisions of five methods were good. The tPSA levels measured by Roche Cobas e601, Snibe MAGLUMI 4000, Mindray CL-2000i, Autobio A2000, and HYBIOME AE180 were 14.11(9.92, 36.09), 12.00(8.56, 27.23), 12.10 (8. 60, 29.87), 13.35(9.51, 32.85) and 14.50(9.88, 40.06) μg/L, respectively. The correlation coeffi-cients of Roche with Snibe MAGLUMI 4000, Mindray CL-2000i, and Autobio A2000 were 0.992, 0.989, 0. 957 and 0.983, respectively (all P<0.001). Assuming the tPSA medical decision point for regression equation was 4.0μg/L, the proportional biases of Snibe MAGLUMI 4000, Mindray CL-2000i, Autobio A2000, and HYBIOME AE180 compared with Roche were -10. 88％, -18. 07％, 0. 23％ and 22. 31％, respectively. Conclusion The comparability of tPSA test results is different between 4 DCIs and Roche ECI, which pro-vides some references for clinical application and standardization of the DCI test results.

Objective To validate the performance of 4 domestic chemiluminescence immunoassay (CLIA) systems on 8 tumor markers quantitative assay kits. Methods Four domestic CLIA systems were randomly marked as A, B, C, D and 8 tumor markers, including carbohydrate antigen (CA)125, CA15-3, CA19-9, ferritin (Fer), alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), prostate-specific an-tigen (PSA) and free PSA (fPSA) were determined. According to the standard of Clinical and Laboratory Standards Institute (CLSI), the precision, methodological comparison and analytical measure range of 4 systems were validated. Clinical serum samples were obtained from patients in Suzhou Hospital. According to the CLSI EP9-A3 protocol, imported equipment was used as the reference system. The biases of medical de-cision points were assumed, and Pearson correlation analysis and Spearman correlation analysis were used to analyze the data. Results The precision verification of CA125 and PSA on A, CA125 and AFP on B, CA125, CEA, AFP and PSA on C, and all 8 tumor markers on D could meet the laboratory quality control requirements. The correlations of the test results between A-D and the imported equipment were significant (all P<0.05) with the correlation coefficients 0.79-0.99, 0.47-0.99, 0.90-0.98 and 0.78-1.00, respec-tively, and the number of acceptable tests at the level of medical decision was 5, 2, 5, 4. All tests were certified to meet the analytical measure range validation. Conclusions The detection performance of 4 do-mestic CLIA systems for all 8 tumor markers are different. The performance of domestic CLIA systems should be tested when choosing one that can meet laboratory quality control requirements.

Objective:To examine the correlation between serum Klotho levels and frailty in elderly people.Methods:In this cross-sectional study, 150 community-dwelling elderly people aged 65 years and over were enrolled.Subjects were divided into a frail(n=50, 33.3%), a pre-frail(n=47, 31.3%)and a non-frail(n=53, 35.3%)group based on the Fried phenotype.General participant data, routine laboratory test results, short physical performance battery(SPPB)results and human body composition data were collected.Serum Klotho protein levels were measured by an enzyme-linked immunosorbent assay.The relationship between serum Klotho protein levels and frailty was analyzed by using Spearmen's correlation analysis and Logistic regression analysis.Results:Klotho protein levels were lower in the frail group than in the non-frail group( P=0.001), whereas differences between the frail group and the pre-frail group and between the pre-frail group and the non-frail group were not statistically significant(all P>0.05).When Klotho protein levels were classified into four quartiles, i.e., Q 1, Q 2, Q 3, and Q 4, using three cut-off vales(2.28, 3.52, and 5.09 mg/L), the prevalences of frailty were 51.4%(19/37), 39.5%(15/38), 24.3%(9/37)and 18.4%(7/38), respectively.The prevalence of frailty decreased with increasing Klotho protein levels( χ2=11.204, P=0.011).Spearman correlation analysis showed that the Klotho protein level was negatively correlated with frailty( r=-0.310, P<0.001).Multivariate Logistic regression analysis results showed that age( OR=1.109, 95% CI: 1.011-1.217, P=0.028)and sarcopenia( OR=6.511, 95% CI: 1.279-33.147, P=0.024)were risk factors for frailty, while walking( OR=0.104, 95% CI: 0.033-0.326, P<0.001), a high SPPB score( OR=0.780, 95% CI: 0.627-0.970, P=0.026), and a high Klotho protein level( OR=0.752, 95% CI: 0.581-0.974, P=0.031)were protective factors against frailty. Conclusions:The serum Klotho protein level may be used as a parameter for the assessment of frailty.It is negatively correlated with frailty, suggesting that elderly people with low serum Klotho protein levels are at high risk of developing frailty.