The aim of this study is to evaluate the ability of the random forest algorithm that combines data on transrectal ultrasound findings, age, and serum levels of prostate-specific antigen to predict prostate carcinoma. Clinico-demographic data were analyzed for 941 patients with prostate diseases treated at our hospital, including age, serum prostate-specific antigen levels, transrectal ultrasound findings, and pathology diagnosis based on ultrasound-guided needle biopsy of the prostate. These data were compared between patients with and without prostate cancer using the Chi-square test, and then entered into the random forest model to predict diagnosis. Patients with and without prostate cancer differed significantly in age and serum prostate-specific antigen levels (P < 0.001), as well as in all transrectal ultrasound characteristics (P < 0.05) except uneven echo (P = 0.609). The random forest model based on age, prostate-specific antigen and ultrasound predicted prostate cancer with an accuracy of 83.10%, sensitivity of 65.64%, and specificity of 93.83%. Positive predictive value was 86.72%, and negative predictive value was 81.64%. By integrating age, prostate-specific antigen levels and transrectal ultrasound findings, the random forest algorithm shows better diagnostic performance for prostate cancer than either diagnostic indicator on its own. This algorithm may help improve diagnosis of the disease by identifying patients at high risk for biopsy.
Bioorthogonal chemistry is widely used in biological systems and has been trialed in patients, attracting a lot of attention in this century. Tetrazine-based bioorthogonal reactions are essential in chemical biology applications, including cellular labeling, live-cell imaging, diagnosis, drug release, and oncotherapy, due to their tunable rapid reaction kinetics and unique fluorogenic characteristics. However, the scope of de novo tetrazine synthesis is restricted due to the limited supply of commercial starting materials. Therefore, derivatization based on tetrazine scaffolds has been used to synthesize various tetrazine derivatives to enhance the applications of tetrazine bioorthogonal reactions. Herein, the recent advances in tetrazine scaffold-based derivatizations, including tetrazine skeletons, aromatic substituents and alkyl substituents of tetrazines, have been summarized. The advantages and limitations of the derivatization methods and applications of the developed tetrazine derivatives in bioorthogonal chemistry have also been highlighted.
Prodrugs, which remain inert until they are activated under appropriate conditions at the target site, have emerged as an attractive alternative to drugs that lack selectivity and show off-target effects. Prodrugs have traditionally been activated by enzymes, pH or other trigger factors associated with the disease. In recent years, bioorthogonal chemistry has allowed the creation of prodrugs that can be chemically activated with spatio-temporal precision. In particular, tetrazine-responsive bioorthogonal reactions can rapidly activate prodrugs with excellent biocompatibility. This review summarized the recent development of tetrazine bioorthogonal cleavage reaction and great promise for prodrug systems.
To prospectively investigate the association between serum uric acid (SUA) level and incidence of impaired fasting glucose (IFG) in adult Chinese. We evaluated 13,328 women and 41,350 men without diabetes and IFG. The participants were classified into quintile according to baseline level of SUA. Data were analyzed to examine the association between SUA levels and the incidence of IFG. We used Cox regression models to estimate the relative risk of IFG after adjusting for known risk factors. For men, the second quintile of SUA has the lowest cumulative incidence of IFG (29.9%); the fifth quintile of SUA has the highest cumulative incidence of IFG (35.6%). After corrected with Cox regression, the first quartile and the fourth quartile have higher cumulative incidence of IFG than the second quintile, with the HR of 1.11(1.05-1.17) and 1.07(1.01-1.13), respectively. For women, the first quartile of SUA has the lowest cumulative incidence of IFG (20.7%), while the fifth quintile of SUA has the highest cumulative incidence of IFG (30.0%). However, there is no significant difference in IFG between different quintile after adjusted with Cox regression. The results of this prospective study suggest that there is a higher risk of developing IFG in association with low or high SUA concentrations for men. These relationships were independent of other known risk factors. There is no significant correlation in the risk of developing IFG in association with SUA concentrations for women. Analyses excluding participants with hypertension or with hyperlipidemia and analyses with participants stratified by age reached similar conclusion.