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Objective:To prepare 89Zr labeled Daratumumab and evaluate its feasibility in the imaging diagnosis of multiple myeloma (MM). Methods:According to the principle of 89Y (p, n) 89Zr nuclear reaction, 89Zr was produced by cyclotron solid target system (30 μA, 1.5 h) and automatic purification module. The radionuclide purity, half-life and impurity metal ion concentration were detected. Desferrioxamine (DFO) was coupled with Daratumumab and then chelated with 89Zr to prepare 89Zr-DFO-Daratumumab. The quality control analyses of three consecutive batches were carried out. Pharmacokinetic evaluation and 89Zr-DFO-Daratumumab microPET/CT imaging were performed in normal rabbits and orthotopic myeloma mouse models, respectively. The SUV in situ myeloma and that in normal bone were compared by independent-sample t test. Results:About 560 MBq of 89Zr was obtained, and there were only two characteristic energy peaks of 89Zr (909 keV and 511 keV) by γ spectrometer. The half-life of 89Zr was 78.2 h, and the content of metal impurities was small. 89Zr-DFO-Daratumumab was prepared with pH of 7.2, radiochemical purity of more than 99%, good stability in vitro, and sterility and endotoxin tests were passed. Pharmacokinetic studies in rabbits showed that 89Zr-DFO-Daratumumab was gradually distributed from blood to liver, spleen, kidney and bone joints over time and metabolism. The results of microPET/CT imaging in orthotopic myeloma mouse models showed that the SUVs of 89Zr-DFO-daratumumab in situ myeloma were significantly higher than those in normal bone (2 h: 0.22±0.02 vs 0.06±0.00; 1 d: 0.38±0.01 vs 0.08±0.00; t values: 8.89, 21.90, both P=0.001). Conclusion:89Zr and 89Zr-DFO-daratumumab are successfully prepared, and relevant quality control and biological evaluation in vivo and in vitro are completed, which verify the feasibility of 89Zr-DFO-Daratumumab in the imaging diagnosis of MM, thus laying a foundation for clinical transformation.
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Objective:To investigate the kinetic metrics of 68Ga-fibroblast activation protein inhibitor (FAPI)-04 in pancreatic cancers and normal organs by using total-body PET dynamic imaging. Methods:From December 2020 to December 2021, 68Ga-FAPI-04 total-body PET/CT dynamic imaging were performed on 6 pancreatic cancer patients (3 males, 3 females, median age 55.5 years) in Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University. Images were respectively analyzed. Manual delineations of volume of interests (VOIs) on multiple normal organs and pathological lesions were performed and time-to-activity curves (TACs) were generated. A reversible two-tissue compartment model (2TCM) was fitted for each tissue TAC. Rate constants including K1, k2, k3 and k4, and the total volume of distribution ( Vt) were obtained and compared by tissue types. Wilcoxon rank sum test and Spearman correlation analysis were used for data analysis. Results:Kinetic metrics varied significantly among normal organs and pancreatic cancer lesions ( z values: 2.00-1 240.00, all P<0.05). The highest K1 among lesions was observed in primary tumor (0.30 min -1), which was observed in the spleen (1.42 min -1) among normal organs. The highest k2 among lesions was observed in peritoneal metastases (0.24 min -1), which was observed in the spleen (2.59 min -1) among normal organs. Primary tumor showed the highest k3 of 0.17 min -1 among lesions, and the pancreas had the highest k3 of 0.16 min -1 among normal organs. Primary tumor had the highest k4 of 0.03 min -1 among lesions, and the heart, lungs, parotid glands had high k4(0.06 min -1) among normal organs. Vt were higher in pathological lesions compared to normal organs, with the highest in primary tumor (13.78 ml/cm 3). There were correlations between Vt in lesions and SUV mean( rs=0.86, P<0.001) or SUV max ( rs=0.77, P<0.001). Conclusion:The rate constants including K1, k2, k3 and k4, and Vt of 68Ga-FAPI-04 vary among normal organs and lesions.
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Objective To explore the curative effect of knee flexion deformity on spastic cerebral palsy treatment method.Methods All of 30 patients with spastic cerebral and knee flexion deformity were randomly divided into two groups:traditional operation group and modified operation group,using the commonly used operation (In 15 cases,with traditional hamstring post surgery) and) modified operation (In 15 cases,with modified hamstring post surgery),two groups of patients were treated with Ilizarov external fixation drafting device in the correction of knee flexion deformity after soft tissue release.Adjustment began 7 days after the soft tissue release operation of external fixation,and stretched approximately 0.2 degrees each time,3 times/d,until knee flexion deformity was corrected to hyperextension for 10 degree and maintained for 3 weeks,and the flexion contracture degree of knee joint was measured every 2 weeks;then the Ilizarov external fixation drafting device was removed.Then wear a walking straight leg brace for more than 3 months,until the knee walking function is good.Clinical evaluation included the joint pain index,walking function index,knee flexion deformity degree and range of joint motion score of Dimeglio standard.Results Flexion contracture deformity of knee joint in 30 cases (60 knees) was corrected when Ilizarov external fixator was removed,knee extension to 0 degrees-5 degrees.The two groups of patients had the knee flexion angle range of-1.2 degrees to 13.3 degrees,with an average of (7.32°±3.41°) after removed of the walking straight leg brace,in which 4 cases (8 joints) got recurrent deformity of 10°-15° at the time of removing of the walking straight leg brace.Knee activity significantly was improved at the end of treatment.60 cases of knee joint activity were close to normal,with flexion of 100 degrees to 135 degrees,extension of 0 degrees to 10 degrees.Two groups of patients were statistically significantly improved before and after surgery.Curative effect comparison:The walking function index of the modified operation group was obviously superior to that of the traditional operation group,there was significant statistical difference.There were no statistically significant differences in pain index,knee flexion,and range of joint motion.Conclusion For the treatment of flexion deformity of the knee joint in spastic cerebral palsy,traditional surgery using the semitendinosus and gracilis,post and semimembranosus lysis,combined with the Ilizarov draft external fixation could improve the walking function of the patients,simplify the surgical incision and reduce trauma.As a result,modified hamstring post surgery is an ideal,effective treatment method.
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OBJECTIVE:To improve the quality of ADR reports. METHODS:By using intensive hospital monitoring mode, ADR reports before and after the application of the system would be collected and factors as report quantity,type,time and quality of reports were analyzed statistically. RESULTS:It provided rapid reporting function after the implementotion of the system. Total quantity of reported ADR cases increased from 589 to 748,and the proportion of all the serious ADR reports increased from 62.8%to 11.76%. The score of repert quality increased from 93.64 to 98.36,the proportion of time-out reports increased from 94.05% to 97.33%,with statistical significance (P<0.05). CONCLUSIONS:Rapid reporting system of ADR in the hospital is beneficial to improve the efficiency and guarantee the quality of the reports. It also can expand the coverage of the monitoring network,and can lay the foundation for drug safety scientific evaluation and monitoring.
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ObjectiveTo study the histologic changes of contracture Achilles tendon under Ilizarov distraction technique.MethodsEighteen dogs were installed ilizarov external fixation frames on the right hind leg in a neutral position.Pull traction started 1 week postoperatively with speed of 1 mm/day for 3 weeks.After 15 degrees of foot drop,the fixation was still maintained for 3 weeks.Nine animals were randomly selected and put to death(Contracture group),other animals corrected for 3 weeks with the same speed and methods,then put to death(Force group),health specimens as control group.(1)Observe tendon cells arranged distribution and collagen fiber form with HE dyeing,and analysis of tendon retinal thickness with image analysis software.(2)Observe collagen Ⅰ and Ⅲ with picrosirius red dying,and analyzed both content changes with image analysis software.(3)Determination of protein contents of polysaccharide with phloroglucinol spectrophotometry.Results (1)In the contracture group,the collagenous fibre gap was not obvious,the tendon cell assumes spindle-shaped,saccate,the collagen fibrous bundle distortion,the arrangement was scattered in disorder,difficult to see the intercellular substance.Tendon retinal thickness showed obvious differences with the health side (Control group).In the force group,the tendon cells were round or oval,located in collagen bundles in a string of alignment,inflammatory cells were seen.Tendon retinal thickness showed no differences with the health side.(2)With polarized light microscopy,the collagen Ⅰ and collagen Ⅲ composition proportion in the contracture group showed obvious differences with the control group,force group had not obvious differences with health side.(3)The content of polysaccharide in the contracture group were obviously reduced,while force group returned to normal level.ConclusionThe tissue form of contracture Achilles tendon can recovered to normal with the Ilizarov technology.
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The field of tissue engineering is paying more attention to bone marrow mesenchymal stem cells.This review focuses on the recent advancement of induced chondrocytes of mesenchymal stem cells including the following aspects: physical conditions of cell culture,growth factors and their regulative mechanism,and gene enhanced tissue engineering.