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Objective:To explore independent risk factors and risk stratification for diagnosis of clinically significant prostate cancer (CsPCa) in biopsy-naive patients with nonsuspicious multiparametric magnetic resonance imaging (mpMRI).Methods:The data of 549 patients who underwent initial systematic biopsy (SB) in the First Affiliated Hospital of Soochow University, the Second Affiliated Hospital of Soochow University and Traditional Chinese Medicine Hospital of Kunshan between October 2015 and January 2021 were retrospectively reviewed. Nonsuspicious mpMRI was defined as Prostate Imaging-Reporting and Data System (PI-RADS)≤2. All patients received systematic 12 core prostate biopsy, 278 of them by transperineal and 271 by transrectal biopsies. The median age of the patients was 67 (62, 73) years, the median prostate specific antigen (PSA) was 9.01 (6.15, 13.64) ng/ml, the median prostate volume was 48.41 (35.85, 64.28) ml, and 54 patients were positive in digital rectal examination (DRE). Taking CsPCa as the outcome index, receiver operating characteristic (ROC) analysis was performed on age, tPSA, f/tPSA and PSA density (PSAD) to obtain the optimal cut-off value, and logistics regression was used to explore the independent risk factor of CsPCa in mpMRI negative patients. The optimal cut-off value when the negative predictive value (NPV) of mpMRI diagnosis of CsPCa was 100%, was taken as the protective factor, and the risk stratification model was finally proposed.Results:Of all 549 cases, 44 were CsPCa, 35 were clinically insignificant prostate cancer and 470 were non-prostate cancer. There were significant differences in age (71 vs. 67 years old), tPSA (11.95 vs. 8.75 ng/ml), PSAD [0.31 vs. 0.18 ng/(ml·cm 3)], f/tPSA (0.12 vs. 0.16) and DRE positive rate (38.6% vs. 7.3%) between CsPCa group and non-CsPCa group ( P<0.01). Cut-off values were taken in ROC analysis when the Youden index was at its maximum. The optimal cut-off values of each continuous variable were: age=65 years, tPSA=10ng/ml, f/tPSA=0.2 and PSAD=0.15 ng/(ml·cm 3). Multivariate analysis showed that ages over 65 years ( OR=3.43, 95% CI 1.55-7.58, P=0.002), f/t PSA ratio<0.2 ( OR=3.84, 95% CI 1.28-11.56, P=0.016), PSAD>0.15 ng/(ml·cm 3) ( OR=3.60, 95% CI 1.13-11.51, P=0.03) and positive DRE ( OR=5.20, 95% CI 2.39-11.32, P<0.001) were independent risk factors of CsPCa. When NPV was 100%, the cut-off values were taken as the protective factors: age≤55 years, f/tPSA≥0.3, PSAD≤0.1 ng/(ml·cm 3). Combined with independent risk factors, preliminary risk stratification was conducted: those with ≥2 high risk factors were considered as high risk group, those with ≥2 protective factors were considered as low risk group, and the middle region was considered as medium risk group. Conclusions:Patients with age>65 years, f/tPSA<0.2, PSAD > 0.15 ng/(ml·cm 3) and DRE positive are independent risk factors of CsPCa in mpMRI negative patients. Patients in the high-risk group were recommended to undergo prostate biopsy, while patients in the low-risk group could be considered to avoid biopsy.
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Objective By using mouse orthotopic lung transplant model, we investigated the immune mechanisms of an-ti-CD3 induced lung allograft protection .Our study intends to further dissect the features of lung transplant immunology and to provide a novel therapeutic insight for the clinical application of anti-CD3 mAbs after lung transplantation.Methods Murine orthotopic allogeneic lung transplants were performed in C57BL/6 wild type(WT) mice using major histocompatibility complex (MHC) fully mismatched BALB/c donors.Syngeneic transplants were also performed in WT C57BL/6 mice using C57BL/6 donors.For immunosuppressive therapy, allograft recipients received 50g dose of anti-CD3 by intraperitoneal injection on days 2, 3, 4, 5, 6 and 9 post-operation(n=4).At day 10, histopathologic characteristics and rejection status of the pulmonary grafts were assessed.The severity of acute rejection was graded by the pathological score , and T cell and neutrophil infiltration in the pulmonary grafts was evaluated by immunohistochemical(IHC) staining for CD3 and myeloperoxidase(MPO) respective-ly.Real-time RT-PCR was performed for FoxP3, IL-17A and IFN-γexpression in the pulmonary grafts.The percentage of FoxP3+Treg in total CD4+T lymphocytes from the recipient spleens was analyzed by FACS.Results 10 days after transplan-tation, histopathologic examination demonstrated that there is no apparent acute rejection observed in the pulmonary isografts , whereas allografts from untreated recipients have marked inflammatory cell infiltration and pulmonary parenchyma lesion .IHC staining for CD3 and MPO showed that the allograft-infiltrating cells of perivascular layers are mainly T lymphocytes , and the cells around the small airways are mostly neutrophils .Anti-CD3 treatment significantly alleviated the acute rejection of pulmo-nary allografts, when compared with the untreated group.Real-time RT-PCR showed that the expression levels of IL-17A and IFN-γin allografts were markedly elevated compared to those in isografts, and anti-CD3 increased the expression of FoxP3, and reduced the expression of IL-17A and IFN-γin the pulmonary allografts.FACS analysis of splenocytes showed that the percent-age of Treg in total CD4+T lymphocytes increased significantly in the anti-CD3 treated allograft recipients, as compared with the isograft and untreated allograft recipients.Conclusion Anti-CD3 mAbs may alleviate acute rejection of the pulmonary al-lografts by promoting FoxP3 expression and Treg development.