1.Efficacy of mIL-18BP and mIL-4 adenoviral coexpression gene therapy for cyclooxygenase-2 and inducible nitric oxide synthetase in murine collagen-induced arthritis
Zhong LU ; Jianhang LENG ; Hangping YAO ; Junya SHEN ; Keyi WANG ; Ziwei WANG ; Guangchao ZHUO
Chinese Journal of Rheumatology 2008;12(9):606-609
Objective A recombinant adenoviral vector containing mIL-18BP and mIL-4 fusion gene(AdmIL-18BP/mIL-4) was constructed and used to investigate the role of mIL-18BP and mIL-4 in medula-ring the expressions of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthetase (iNOS) and their inducing products PGE2, NO in murine collagen-induced arthritis. Methods Male DBA-1/BOM mice were used in this study. Mice with CIA were intra-articularly injected with 107 pfu/6μl of AdmIL-18BP/mIL-4.Intra-articular injections of AdLacZ or PBS were used as controls. The mRNA expression of COX-2, iNOS in synovial tissue was analyzed by semi-quantitative RT-PCR. Expression of COX-2 and iNOS protein was estimated by Western blot method. The production of PGE2 and NO in synovia was detected by competitive ELISA and enzyme reduction of nitrate. Results The expression of COX-2, iNOS mRNA in routine synovial tissue of AdmIL-18BP/mIL-4 treatment group was significantly lower than that of AdLacZ group (0.15 vs 0.42,P<0.01 ; 0.05 vs 0.77, P<0.01) and PBS group (0.15 vs 0.65, P<0.01; 0.05 vs 0.64, P<0.01 ). And the protein expression of COX-2, iNOS from AdmIL-18BP/mIL-4 treatment group was also obviously lower than that of AdLacZ group (0.08 vs 0.92, P<0.01; 0.11 vs 1.00, P<0.01) and PBS group (0.08 vs 0.77, P<0.01; 0.11 vs 0.84, P<0.01 ). The PGE2 and NO production in synovia of AdmIL-18BP/mIL-4 treatment group was significantly lower than that of AdLacZ group [(0.68x0.06) vs (2.58±0.21)ng/mL, P<0.01; (23.4+2.5) vs (60.0±11.3)μmol/L, P<0.01 ] and PBS group [(0.68±0.06) vs (2.57±0.20)ng/mL, P<0.01; (23.4+2.5) vs (60.3±13.4)μmol/L, P<0.01]. Conclusion These data indicat that local over-expre-ssion of mIL-18BP and mIL-4 can down-regulate COX-2, iNOS and their induced product PGE2, NO in CIA mice. The combination treatment with mIL-18BP and mIL-4 is a promising therapeutic target for RA.
2.A method of dynamic scatter correction for direct 4?dimensional PET parametric imaging
Keyi LU ; Baoxin CHEN ; Jianhua YAN
Chinese Journal of Nuclear Medicine and Molecular Imaging 2018;38(10):685-688
Objective To propose a method of dynamic scatter correction for direct 4-dimensional (4D) PET parametric image reconstruction. Methods Scatter correction for direct 4D PET parametric im-age reconstruction was achieved by extending 3-dimensional (3D) static single scatter simulation (SSS) into 4D dynamic SSS with the help of spatiotemporal cubic polynomial interpolation. The 2 h-serotonin transporter tracer 11 C-2-(2-(dimethylaminomethyl)phenylthio)-5-fluoromethylphenylamine (AFM) brain List mode data of 3 volunteers were obtained from a human brain-dedicated high resolution research tomograph (HRRT) PET scanner. Parametric images (K1 and VT ) were reconstructed by both conventional frame-based method (FM) and direct 4D method. Estimated scatter fractions by both methods were compared. Paired t test was used to analyze the data. Results Scatter fractions derived from FM and direct 4D method were 30.1%(6. 35×107 / (2.11× 108 )), 32.0% (6.82× 107 / (2.13× 108 )) and 34.4% (7.22× 107 / (2.10× 108 )), 30. 0%(6.33×107 / (2.11×108 )), 33.3%(7.10×107 / (2.13×108 )) and 34.1%(7.16×107 / (2.10×108 )) for the three subjects, respectively (t = -0.002, P>0.05). Scatter fractions obtained by the two methods were comparable. There was no significant difference between K1(FM: (0.51±0.11) ml·min-1 ·cm-3 , 4D: (0.48±0.09) ml·min-1 ·cm-3) and VT (FM: (24.77±11.80) ml/ cm3, 4D: (27.85±12.65) ml/ cm3) in the two methods (t values: -0.01, -0.97, both P>0.05). Conclusion The proposed dynamic scatter cor-rection method can be used for direct 4D parametric imaging and make it feasible for clinical use.
3.Mechanism of PD-L1 in thyroid carcinoma and its application in diagnosis and treatment
Yuping WU ; Xiaoyu ZHANG ; Keyi LU
Journal of International Oncology 2021;48(9):560-563
Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) participate in the regulation of immune checkpoint and are closely related to the occurrence and development of thyroid carcinoma. PD-L1 is expressed differently in different types of thyroid cancer and can be used as a biomarker for the diagnosis of some tumors. The expression of PD-L1 in thyroid cancersis associated with higher tumor invasiveness and higher risk of recurrence. PD-1/PD-L1 immune checkpoint is a promising target for the treatment of some thyroid cancers. Further discussion of the mechanism of PD-1/PD-L1 pathway and its role in the diagnosis and treatment of thyroid cancer and the biomarkers related to the therapeutic effect can provide new ideas for the diagnosis and treatment of thyroid cancer.
4.Application of radionuclide renal dynamic imaging combined with double plasma method in evaluation of split renal glomerular filtration rates pre- and post-interventional treatment in patients with unilateral hydronephrosis
Yuping WU ; Keyi LU ; Xiaoyu ZHANG ; Congge LI ; Guang HU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2022;42(8):473-477
Objective:To explore the value of 99Tc m-diethylene triamine pentaacetic acid (DTPA) renal dynamic imaging combined with double plasma glomerular filtration rate (GFR) in the evaluation of split renal function in adult patients undergoing interventional therapy for unilateral hydronephrosis. Methods:Retrospective analysis of 79 patients (39 males, 40 females, age (41.4±16.3) years) with unilateral hydronephrosis in First Hospital of Shanxi Medical University from January 2015 to December 2019 were performed. All patients underwent surgery to relive obstruction. 99Tc m-DTPA renal dynamic imaging was performed before and after surgery to obtain bilateral renogram and GFR was measured by Gates method (marked as gGFR). Meanwhile, the corrected double plasma method was used to measure the GFR of both kidneys (marked as dGFR all). Double plasma GFR of the affected kidney (marked as dGFR) was obtained according to the ratio of renogram and dGFR all. Patients were divided into mild to moderate group (dGFR≥20 and <40 ml·min -1·1.73 m -2 ), severe group (dGFR≥10 and <20 ml·min -1·1.73 m -2) and extremely severe group (dGFR<10 ml·min -1·1.73 m -2) according to dGFR before surgery. Postoperative renal dynamic imaging and dGFR were reexamined to analyze the GFR recovery values (ΔgGFR, ΔdGFR). Data were analyzed by χ2 test, paired t test, one-way analysis of variance, Pearson correlation analysis and Bland-Altman consistency test. Results:There were 34 patients in mild to moderate group, 24 patients in severe group, 21 patients in extremely severe group. Significant differences were found in both gGFR and dGFR before and after surgery in mild to moderate group, as well as those in the extremely severe group ( t values: 2.42-3.34, all P<0.05 ), but there was no significant difference in severe group ( t values: 1.24, 1.27, both P>0.05). The ΔgGFR and ΔdGFR were not significantly different among three groups ( F values: 0.45, 0.34, both P>0.05). GFR mesured by the 2 methods (gGFR, dGFR) before and after operation correlated well in each group (before surgery, r values: 0.68-0.82; after surgery, r values: 0.80-0.91, all P<0.001). GFR measured by the two methods showed poor consistency in the mild to moderate and severe groups (>5%(5.88%, 2/34; 8.33%, 2/24) values before and after surgery exceeding 95% consistency limit), while good consistency was demonstrated in the extremely severe group (<5%(4.76%, 1/21) values before and after surgery exceeding 95% consistency limit). Conclusions:Preoperative GFR in patients with unilateral hydronephrosis cannot predict the recovery of renal function after interventional treatment. For the evaluation of split renal GFR in patients with unilateral upper urinary tract obstructive hydronephrosis, corrected dual plasma method combined with kidney ratio of renogram is more appropriate for the determination of GFR. Gates method has some limitations, however, it can be recommended for the evaluation of GFR in patients with extremely severe renal impairment before and after interventional surgery.