Application of 3.0T multiparametric magnetic resonance imaging prostate imaging-reporting and data system V2.1 score combined with prostate-specific antigen density in the diagnosis of prostate cancer / 肿瘤研究与临床

Objective:To investigate the application of 3.0T multiparametric magnetic resonance imaging (Mp-MRI) prostate imaging-reporting and data system (PI-RADS) V2.1 score combined with prostate-specific antigen density (PSAD) in the diagnosis of prostate cancer (PCa).Methods:The clinical data of 82 patients with suspected PCa who were admitted to Nantong Second People's Hospital from May 2017 to Octorber 2021 were retrospectively analyzed. The 3.0T Mp-MRI PI-RADS V2.1 score, serum PSAD level and pathological diagnosis were obtained from all patients. The 3.0T Mp-MRI PI-RADS V2.1 score and its distribution as well as serum PSAD level between patients with pathologically diagnosed PCa and patients with prostatic hyperplasia (BPH) were compared. The diagnostic efficiency of 3.0T Mp-MRI PI-RADS V2.1 score and serum PSAD level alone and in combination for PCa was analyzed using receiver operating characteristic (ROC) curve, with pathological results as the gold standard.Results:Pathological diagnosis showed that there were 43 cases (52.44%) of PCa and 39 cases (47.56%) of BPH. There was a statistical difference in the distribution of 3.0T Mp-MRI PI-RADS V2.1 score between PCa and BPH patients ( Z = 32.25, P<0.001). The 3.0T Mp-MRI PI-RADS V2.1 score of PCa patients was higher than that of BPH patients [(4.29±0.25) points vs. (2.24±0.11) points, P < 0.001], the serum PSAD level was higher than that of BPH patients [(0.49±0.15) ng·ml -1·cm -3 vs. (0.27±0.08) ng·ml -1·cm -3, P < 0.001]. The ROC curve analysis showed that area under the curve of 3.0T Mp-MRI PI-RADS V2.1 score, serum PSAD level alone and both together for the diagnosis of PCa were 0.766 (95% CI 0.659-0.852, P < 0.001), 0.793 (95% CI 0.689- 0.874, P < 0.001) and 0.816 (95% CI 0.715-0.893, P < 0.001). Conclusions:3.0T Mp-MRI PI-RADS V2.1 score and serum PSAD level are both elevated in PCa patients. They have certain values in the diagnosis of PCa, and the combination of the two has higher diagnostic efficiency.

The bias assessment and comparability analysis of upgraded estradiol kit / 国际检验医学杂志

Objective To evaluate the consistency of estradiol kits between E2-Ⅲ and the upgraded Enhanced Estradiol(eE2)kit with chemiluminescence immunoassay analyzer Siemens ADVIA Centaur.Methods Used duplicate samples and removed outliers to test the two reagents′stability;document EP9-A2 were used as reference to do the methodological comparison and bias estimation. Results There was good correlation between the two reagents with different concentrations,the correlation coefficients were grea-ter than 0.975;the percentage of bias was varied among different groups.Conclusion It is effective to reduce the interference of up-dated estradiol kits on the assisted reproduction treatment cycles by assessing the bias through comparison tests of the two kits in advance.

Coronavirus membrane-associated papain-like proteases induce autophagy through interacting with Beclin1 to negatively regulate antiviral innate immunity

Autophagy plays important roles in modulating viral replication and antiviral immune response. Coronavirus infection is associated with the autophagic process, however, little is known about the mechanisms of autophagy induction and its contribution to coronavirus regulation of host innate responses. Here, we show that the membrane-associated papain-like protease PLP2 (PLP2-TM) of coronaviruses acts as a novel autophagy-inducing protein. Intriguingly, PLP2-TM induces incomplete autophagy process by increasing the accumulation of autophagosomes but blocking the fusion of autophagosomes with lysosomes. Furthermore, PLP2-TM interacts with the key autophagy regulators, LC3 and Beclin1, and promotes Beclin1 interaction with STING, the key regulator for antiviral IFN signaling. Finally, knockdown of Beclin1 partially reverses PLP2-TM's inhibitory effect on innate immunity which resulting in decreased coronavirus replication. These results suggested that coronavirus papain-like protease induces incomplete autophagy by interacting with Beclin1, which in turn modulates coronavirus replication and antiviral innate immunity.

SARS coronavirus papain-like protease inhibits the type I interferon signaling pathway through interaction with the STING-TRAF3-TBK1 complex

SARS coronavirus (SARS-CoV) develops an antagonistic mechanism by which to evade the antiviral activities of interferon (IFN). Previous studies suggested that SARS-CoV papain-like protease (PLpro) inhibits activation of the IRF3 pathway, which would normally elicit a robust IFN response, but the mechanism(s) used by SARS PLpro to inhibit activation of the IRF3 pathway is not fully known. In this study, we uncovered a novel mechanism that may explain how SARS PLpro efficiently inhibits activation of the IRF3 pathway. We found that expression of the membrane-anchored PLpro domain (PLpro-TM) from SARS-CoV inhibits STING/TBK1/IKKε-mediated activation of type I IFNs and disrupts the phosphorylation and dimerization of IRF3, which are activated by STING and TBK1. Meanwhile, we showed that PLpro-TM physically interacts with TRAF3, TBK1, IKKε, STING, and IRF3, the key components that assemble the STING-TRAF3-TBK1 complex for activation of IFN expression. However, the interaction between the components in STING-TRAF3-TBK1 complex is disrupted by PLpro-TM. Furthermore, SARS PLpro-TM reduces the levels of ubiquitinated forms of RIG-I, STING, TRAF3, TBK1, and IRF3 in the STING-TRAF3-TBK1 complex. These results collectively point to a new mechanism used by SARS-CoV through which PLpro negatively regulates IRF3 activation by interaction with STING-TRAF3-TBK1 complex, yielding a SARS-CoV countermeasure against host innate immunity.