Objective To establish stable Graves disease (GD) mice models with immunization and electroporation (EP).Methods Fifty mice were divided into 3 groups by random number table method:experimental group (n =30),control group (n =10),blank group (n =10).Recombinant plasmid pcDNA3.1/hTSHR268 was constructed and injected to bilateral gastrocnemius in experimental group mice on the 1st,4th,7th and 10th week.The same volume of normal saline was injected in the control group and blank group at the same time.Both experimental group and control group were subjected to EP at the same time and the same location to enhance immunization.Serum T4 was tested with radioimmunoassay.TRAb N-terminal (TRAb N) and TRAb C-terminal (TRAb C) antibodies were tested with ELISA.Whole body 99TcmO4-imaging was performed and then thyroid morphology and pathology were investigated.Data were analyzed by one-way analysis of variance and the least significant difference (LSD) t test.Results GD BALB/c mice models were built successfully (80％,24/30).Serum T4 increased from (16.06±5.16) nmol/L at the basic level to(95.04±68.92) nmol/L on the 12th week(F=18.906,t=-5.598,P＜0.05).Serum TRAb N antibody increased from (0.006±0.002) U/L at the basic level to (0.251±0.110) U/L on the 12th week(F=47.491,t=-10.869,P＜0.05).Serum TRAb C antibody increased from (11.176±2.635)×103 arbitrary unit (AU)/L at the basic level to (46.395±22.001)× 103 AU/L on the 12th week(F=14.642,t =-7.787,P＜0.05).On the 18th week serum T4,TRAb N and TRAb C decreased to (36.64±23.68) nmol/L,(0.094±0.053) U/L and (24.456±6.725)× 103 AU/L respectively,which were still higher than those preimmune levels(t=-4.161,-8.085,-9.008,all P＜0.05).There were no significant change of T4,TRAb N and TRAb C in the control group and blank group.After 4 times of immunization,the 99TcmO4-uptake by thyroids in immunized mice increased.The thyroid glands of immunized mice showed enlargement.Microscope examination showed that there were lymphocytes infiltration,colloid decrease and epithelial cell proliferation in thyroids of immunized mice.Conclusion GD mice models were successfully established by injecting recombinant plasmid pcDNA3.1/hTSHR268 and EP.

Objective To establish radioiodine therapy in nonthyroid tumor and to investigate 131Ⅰ treatment effect on xenografted ovarian cancer. Methods Based on previous test, xenografted ovarian cancer nude model were established in nude mice. The effects of radioactive isotope 99m TcO-4 imaging and radioiodine 131Ⅰ treatment on xenografted ovarian cancer in vivo were investigated. Results After transferring human sodium/iodide symporter (hNIS) gene, the xenografted ovarian cancer in nude mice was imaged by isotope 99m TcO-4 Moreover,131Ⅰ exerted inhibitory effect on the proliferative activity. Conclusion After the transfection of hNIS gene, 131Ⅰ has inhibitory effect on proliferative activity of xenografted ovarian cancer.

Objective To explore the possibility of using 131I as a targeted therapy method for malignant glioma by infecting U87 and U251 cells with conditionally replicative adenovirus Ad-Tp-E1a-Gp-NIS.Methods Human telomerase reverse transcriptase (hTERT) promoter and glial fibrillary acidic protein (GFAP) promoter were cloned and their transcriptional activities were detected by luciferase assay.The conditionally replicative adenovirus Ad-Tp-E1 a-Gp-NIS was constructed,purified,and transfected into U87 and U251 glioma cells.For these transfected cells,the selective replication ability was evaluated by plaque forming assay,and protein expression was detected by Western blot assay.125I-iodide uptake and exflux,the clonoy formation of 131I-iodide treated cells were also measured.Results Transcriptions activity of the GFAP and hTERT promoters was 59.75％-62.10％ (F =11.89,P ＜ 0.01) in U87 cells and 37.31％-49.00％ (F =5.87,P ＜ 0.05) in U251 cells.The Ad-Tp-E1a-Gp-NIS could be selectively replicated and the hNIS gene was successfully expressed in the hTERT-positive and GFAP-positive glioma cells which showed two protein bands with relative molecular mass of 120 × 103 and 49 × 103 in Western blot assay.After infection with Ad-Tp-E1a-Gp-NIS,the cell ability of 125I uptake was increased by 78.80 (F =2 914.58,P ＜0.01) and 92.48 (F =2 275.91,P ＜0.01) times in U87 and U251 cells,respectively.The GFAP-negative MRC-5 cells could not take in 125I.The in vitro clonogenic assay indicated that,after 131I treatment,more than 90％ of the transfected cells were killed,while only about 65％ (t =11.73-78.33,P ＜ 0.01) of control cells were killed.Conclusions The Ad-Tp-E1a-Gp-NIS has a good ability in selective replication and the enhancement of antitumor therapy effect by increasing tumor-specific iodide uptake in malignant glioma cells.

Objective:To investigate the risk factors of musculoskeletal disorders(MSDs)in dental postgraduates.Methods:271 dental postgraduates majoring in five different specialties(orthodontics,prosthodontics,endodontics,periodontics and alveolar surgery) with average (2.78 ±1 .57)years of clinical practice were recruited.254 age-matched non-dental postgraduates were served as the controls.The standardized Nordic questionnaire on MSDs and a self-report questionnaire regarding correlative factors were answered. Reliability of the responses was assessed by applying test-retest method.Results:The test-retest method revealed a high reliability of participants'answers with the intraclass correlation coefficient ranging from 0.89 to 0.96.Dental postgraduates had significantly higher incidence (85.6%)of MSDs than the controls(70.4%).In all included dental specialties,high prevalence of MSDs was reported at neck (47.5%-69.8%),followed by shoulders (50.8%-65.1 %),lowerback (27.1 %-51 .2%)and upper back (25.6%-46.5%).Meanwhile,the high prevalence of MSD varied in different specialties.Year of clinical work,clinical hours per week and desk hours per week were found to be the risk factors for MSDs,whereas physical exercise and rest were protective factors.Conclu-sion:MSDs with high prevelence and distinct specialty-related characteristics initiate at the early stage of dental career.Relevant measures to prevent and protect against MSDs should be taken during school-days.

Objective To investigate the effect of all trans-retinoic acid (ATRA) combining with Interferon α-2a on bladder tumor and the possible mechanisms. Methods Fifty female Wistar rats with bladder tumor were established and separated into 4 groups randomly that are DMSO group (A), IFN-α-2a group(B), ATRA group(C) and ATRA+IFN-α-2a group(D). Then each group was treated by drugs indicated. Finally, the weight of bladder, the stage and grade of tumor, the apoptosis and proliferation index of tumor were determined to estimate the effect of ATRA+IFN-α-2a. Results The body weights in group D are the highest and the bladder weights in group D are the lowest. The stages and grades of tumor in group D were statistically decreased compared with those in the other 3 groups. Accordingly, the apoptosis of cancer cells in group D was enhanced, whereas the proliferation index in group D was decreased significandy. Conclusion The effect of ATRA combined with Interferonα-2a on the bladder tumor is better than that of monotherapy.

0.05).Conclusion The PAI-1 genotype perhaps may not be one of independent risk factors for both T2DM and FA-IMT in T2DM patients.

Objective To investigate the biological effects of internal radiation and therapeutic effectiveness of 131I-labeled anti-epidermal growth factor receptor (EGFR) in colorectal cancer of model mice.Methods Nano-liposome characterized for EGFR-targeting was constructed.The efficacy of cellular binding and uptake of the liposome was evaluated by the analysis of confocal microscopy observation and the iodide uptake assay.After intra-tumor injections of 74 MBq (740 MBq/ml) 131 I-antiEGFR-BSA-PCL,131 I-BSA-PCL,131 I or an equivalent volume of normal saline.The biological effects of internal irradiation and therapeutic efficacy of the liposomes on colorectal cancer modeled in a male BALB/c mouse were evaluated by means of tumor size,body weight,histopathology,and SPECT imaging.Results The confocal fluorescence images showed that the antiEGFR-BSA-PCL was successfully internalized into LS180 cells.The 131I uptake efficacy of 131I-antiEGFR-BSA-PCL was significantly higher than that of 131I-BSA-PCL in LS180 cells (t =2.77-5.40,P ＜ 0.01).Tumor size measurement showed that tumor growth was inhibited by the treatment with 131 I-EGFR-BSA-PCL and 131I-BSA-PCL,but had no significant differences between these two groups (P ＞0.05).It was found that the 131I-antiEGFR-BSA-PCL was markedly taken up by the tumor and reac hed its uptake value of (21.61 ± 1.0 1) and (20.58 ± 0.65)％ ID/g at 72 h following drug injection,which was higher than the uptake value of 131 I (t =9.36,8.69,P ＜ 0.01).SPECT imaging assay showed that,after being injected into mouse tumor,the 131 I-EGFR-BSA-PCL and 131I-BSA-PCL were uniformly distributed inside the tumor.Conclusions 131 I-antiEGFR-BSA-PCL obviously suppresses the development of colorectal cancer in mice.

Objective To construct 131 I labeled anti?EGFR immunoliposome nanoparticle ( 131 I?Cetuaximab ( C225)?BSA?PCL) , and investigate its inhibitory effect on EGFR?overexpressing cancer cells in vitro. Methods Anti?EGFR liposome nanoparticle C225?BSA?PCL and non?targeted liposomes BSA?PCL were constructed. The products were observed with transmission electron microscopy and dynamic light scat?tering. The EGFR?targeted binding and cellular uptake in EGFR?overexpressing cancer cells were observed with flow cytometry and confocal microscopy. Anti?EGFR and non?targeted liposomes were labeled with 131 I using the chloramine?T method. The targeted cell killing effects of 131 I labeled liposomes were analyzed using MTT assay. The time?dependent cellular uptake analysis was used to evaluate the slow?release effects of the 131 I labeled liposomes. The independent?samples t test was used for data analysis. Results The EG?FR?targeted liposome C225?BSA?PCL and non?targeted liposome BSA?PCL were successfully constructed, and the effective diameters were approximately 130-180 nm. Flow cytometry and confocal microscopy re?vealed significant uptake of C225?BSA?PCL in EGFR?overexpressing tumor cells. BSA?PCL could also bind to cells with minimal and weak tumor retention. The EGFR?targeted radioactive liposome 131I?C225?BSA?PCL showed greater targeted cell killing effect than non?targeted liposome 131I?BSA?PCL,the IC50 values of 131I?C225?BSA?PCL and 131 I?BSA?PCL were 0. 03-1. 32 and 0. 25-12. 19, respectively. The uptakes of 131 I?C225?BSA?PCL was higher than that of 131 I?BSA?PCL ( t=3.03-16.86, all P<0.05) and reached the maxi?mal level at 4 h after incubation. Conclusions The EGFR?targeted liposome C225?BSA?PCL demonstrated superior cellular binding and uptake on EGFR?overexpressing cancer cells compared with BSA?PCL. The EGFR?targeted radioactive liposome 131 I?C225?BSA?PCL had favorable intracellular retention and excellent targeted cell killing effect, and could effectively suppress the growth of EGFR?overexpressing cancer cells.

Objective:To explore the impact of urinary iodine concentration (UIC) on response to 131I treatment in differentiated thyroid cancer (DTC) patients with different risk stratifications. Methods:A total of 181 patients with DTC (75 males, 106 females, age: (44.1±12.5) years), who received the first 131I treatment in Tianjin Medical University General Hospital between January 2018 and February 2019, were retrospectively analyzed. Patients were divided into low- to intermediate-risk and high-risk groups. The treatment response was categorized into excellent response (ER) and non-excellent response (non-ER). Factors being evaluated including age, sex, preablative stimulated thyroglobulin (ps-Tg), UIC, etc. Mann-Whitney U test, χ2 test and logistic regression analysis were used for data analysis. Results:The UIC and ps-Tg in the low- to intermediate-risk group ( n=113) was 111.60(55.80, 204.65) μg/L and 2.08(0.63, 4.91) μg/L, respectively. Compared with the ER subgroup ( n=86), non-ER subgroup ( n=27) had higher UIC and ps-Tg level ( z values: -2.585, -4.511, both P<0.05). In the high-risk group ( n=68), UIC was 115.40(61.23, 167.28) μg/L and ps-Tg was 16.65(4.52, 43.45) μg/L. Compared with the ER subgroup ( n=20), non-ER subgroup ( n=48) had higher ps-Tg level ( z=-4.677, P<0.01), while the UIC was not significantly different between ER and non-ER subgroups ( z=-0.013, P>0.05). The multivariate logistic analysis indicated the ps-Tg level was the significant variable for non-ER in low- to intermediate-risk group (odds ratio( OR)=6.157(95% CI: 1.046-36.227); OR=22.965(95% CI: 3.591-146.857), both P<0.05) and high-risk group ( OR=9.696 (95% CI: 1.379-68.169), P<0.05); a high UIC could be an indicator of non-ER only in the low- to intermediate-risk group ( OR=3.715(95% CI: 1.201-11.488), P<0.05). Conclusions:The non-ER is associated with UIC in the low- to intermediate-risk group; however, UIC does not affect the non-ER in the high-risk group. Higher ps-Tg level is associated with non-ER in patients with low- to intermediate-risk and high-risk DTC.

OBJECTIVETo explore the possibility of tranfecting hNIS and hTPO genes into gliomas cells by recombinant adenovirus for radioactive iodide treatment.

METHODSTo tranfect hNIS gene into human glioma cell line U251 by recombinant adenovirus. The biological functions of the cells stably expressing hNIS and hTPO genes were assessed by (125)I uptake assay, (125)I influx-course and (125)I-efflux-course. A glioma model was established with inoculation of the U251 cells in nude mice, and the inhibiting effect of (131)I on the tumor growth was tested in the mouse models.

RESULTSThe hNIS and hTPO genes were successfully transfected into human gliomas cell line U251 cells by recombinant adenovirus. The radioactive iodide could be intaken by the tumor cells mediated by hNIS gene. The uptake of (125)I was higher in cell lines hNIS-U251 and hNIS-hTPO-U251 cells than in cell line U251 cells. The tumor volume of the mice after (131)I treatment was significantly decreased in comparison with that before treatment.

CONCLUSIONRadioactive (131)I treatment after HNIS-based gene transfer can be enhanced and effectively inhibit the tumor growth in nude mice.

Adenoviridae ; genetics ; Animals ; Brain Neoplasms ; pathology ; therapy ; Genetic Therapy ; Glioma ; pathology ; therapy ; Humans ; In Vitro Techniques ; Iodides ; Iodine Radioisotopes ; metabolism ; therapeutic use ; Mice, Nude ; Symporters ; genetics ; Transfection