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Objective:To explore the therapeutic mechanism of Mongolian medicine Sendeng-4 decoction for rheumatoid arthritis by 99Tc m-hydrazinonicotinamide-(polyethylene glycol) 4-E[(polyethylene glycol) 4-c((Arg-Gly-Asp)fk)] 2 (3PRGD 2) imaging. Methods:A total of 200 female SD rats (age: 6-7 weeks) were divided into collagen-induced arthritis (CIA) group ( n=176) and blank control group ( n=24). Rats in the CIA group were divided into Sendeng-4 decoction treatment group ( n=24), etanercept treatment group ( n=24), and negative control group ( n=24) by simple random sampling method. 99Tc m-3PRGD 2 SPECT/CT imaging was performed before and after modeling and treatment. The differences of target/non-target (T/NT) ratio and serological, pathological, and immunohistochemical results among groups were compared by one-way analysis of variance or Kruskal-Wallis rank sum test. The correlation was analyzed by Pearson correlation or Spearman correlation analysis. Results:There were 95 (95/176) CIA models successfully established. The T/NT ratios of Sendeng-4 decoction treatment group and etanercept treatment group were lower than that of negative control group (0.260± 0.094, 0.238±0.099, 0.766±0.144 ; F=163.00, P<0.001), while there was no significant difference between the two drug treatment groups ( P>0.05). After drug treatment, serum levels of vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α) and α vβ 3 were significantly lower than those of negative control group ( F values: 49.43-92.36, all P<0.001), pathological score was also lower than that of negative control group ( H=34.25, P<0.001), and levels of immunohistochemical makers (VEGF, TNF-α, α vβ 3, CD31, CD34) were also lower than those of negative control group ( H values: 13.51-26.84, all P<0.001), while there were no significant differences between the two drug treatment groups (all P>0.05). The T/NT ratios were positively correlated with above indictors in Sendeng-4 decoction treatment group ( r values: 0.56-0.59, rs values: 0.49-0.69), etanercept treatment group ( r values: 0.50-0.55, rs values: 0.46-0.70) and negative control group ( r values: 0.55-0.80, rs values: 0.58-0.86, P<0.001 or P<0.05). Conclusion:Verified by 99Tc m-3PRGD 2 SPECT/CT imaging and molecular pathology, Mongolian medicine Sendeng-4 decoction can inhibit neovascularization by down-regulating vascular factors such as VEGF, resulting in delaying the progression of the disease and improving clinical symptoms.
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Objective:To evaluate the value of 99Tc m-hydrazinonicotinamide-(poly-(ethylene glycol)) 4-E((poly-(ethylene glycol)) 4-c((Arg-Gly-Asp)fK)) 2 (3PRGD 2) imaging on predicting pathological complete response (pCR) outcomes to neoadjuvant chemotherapy (NAC) in patients with breast cancer and to compare it with 18F-FDG imaging. Methods:From October 2017 to October 2019, 41 patients (age: (61.5±7.8) years) who were diagnosed with stage Ⅱ and Ⅲ breast cancer and planned to receive preoperative NAC in the First Affiliated Hospital of Fujian Medical University and Xiehe Affiliated Hospital of Fujian Medical University were prospectively enrolled. All patients underwent both 99Tc m-3PRGD 2 and 18F-FDG imaging before NAC (baseline), and after the first and the fourth NAC cycle. The tumor/background ratio (T/B; 99Tc m-3PRGD 2) and SUV max ( 18F-FDG) in breast tumors and axillary lymph node (ALN) metastases were separately calculated. The relative T/B changes (ΔT/B 1, ΔT/B 2) and SUV max changes (ΔSUV max1, ΔSUV max2) after the first and the fourth NAC cycle compared to baseline were obtained. Patients underwent surgery after NAC and the pathology was used as the gold standard to determine whether patient achieved pCR. The predictive performance of ΔT/B and ΔSUV max regarding the identification of pCR or non-pCR was evaluated by using ROC analysis and the AUCs were compared by Delong test. Results:Of 41 patients, 13 (31.7%) were achieved pCR after NAC. For breast tumors, the AUCs of ΔT/B 1, ΔT/B 2, ΔSUV max1 and ΔSUV max2 were 0.827 ( P=0.001), 0.687 ( P=0.057), 0.859 ( P<0.001) and 0.713 ( P=0.030) respectively, and the AUCs of ΔT/B 1 and ΔSUV max1 had no significant difference ( z=0.33, P=0.740). For ALN metastases, the AUCs of ΔT/B 1, ΔT/B 2, ΔSUV max1 and ΔSUV max2 were 0.859 ( P=0.002), 0.778 ( P=0.014), 0.572 ( P=0.523) and 0.802 ( P=0.007) respectively, and the AUC of ΔT/B 1 was significantly higher than that of ΔSUV max1 ( z=2.10, P=0.035). Conclusion:The early relative changes of breast tumors and ALN metastases in 99Tc m-3PRGD 2 imaging during NAC can offer predictive information for pCR to NAC in patients with breast cancer, and early relative changes of ALN metastases in 99Tc m-3PRGD 2 imaging may have a higher predictive value for pCR than 18F-FDG imaging.
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Objective Anti-calcification and surface modification of the transcatheter heart valve is the priority research area and development direction of bioprosthesis heart valve.In present study,the Arginine-Glycine-Aspartic acid(RGD) coating technology and anti-calcification with epoxy chloropropane(EC) treatment were applied to investigate surface modification property of the transcatheter heart valve compared to the traditional anti-calcification method with glutaraldehyde (GA) treatment to demonstrate the improvement of structure and surface biological properties of the transcatheter heart valve.Methods Morphological characteristics of mesenchymal stem cells(MSCs) seeded on the transcatheter heart valve with the various anticalcification treatments were observed by scanning electron microscopy and the apoptosis rates of MSCs seeded on the transcatheter heart valve with the various anti-calcification interventions were studied by TUNEL staining.The cell adhesion and expression of the cytoskeletal protein,Vinment of MSCs treated as described were analyzed by cell-counting method and fluorescence immunohistochemical method respectively.Results The apoptosis rate of MSCs was markedly decreased while the expression of vinment and the cell adhesion strength of MSCs were elevated in the groups of GA-EC and RGD-EC treatments.The biological indices of RGD-EC group has significant difference(P ＜ 0.05) compared with GA group.Conclusion Biological properties of the surface of transcatheter heart valve can be remarkably improved by GA-EC and RGD-EC anti-calcification treatments.
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RGD-containing peptides onto decellularized valve scaffolds. And the technique can effectively promote cell adhesion, which is beneficial for in vitro tissue engineering of heart valves.