This study aimed to assess the role of prostate-specific antigen density (PSAD) and negative multiparametric magnetic resonance imaging (mpMRI) in predicting prostate cancer for biopsy-naïve men based on a large cohort of the Chinese population. From a prostate biopsy database between March 2017 and July 2021, we retrospectively identified 240 biopsy-naïve patients with negative prebiopsy mpMRI (Prostate Imaging Reporting and Data System version 2 [PI-RADS v2] score <3). Logistic regression analysis was performed to select the potential predictors for clinically significant prostate cancer (csPCa). Receiver operating characteristic (ROC) curve analysis and area under the ROC curve (AUC) were performed to assess the diagnostic accuracy. The negative predictive values of mpMRI in excluding any cancer and csPCa were 83.8% (201/240) and 90.8% (218/240), respectively. ROC curve analysis indicated that PSAD was the most promising predictor, with an AUC value of 0.786 (95% confidence interval [CI]: 0.699–0.874), and multiparametric logistic regression analysis confirmed that higher PSAD remained a significant marker for predicting csPCa (odds ratio [OR]: 10.99, 95% CI: 2.75–44.02, P < 0.001). Combining negative mpMRI and PSAD below 0.20 ng ml −2 obviously increased the predictive value in excluding PCa (91.0%, 101/111) or csPCa (100.0%, 111/111). If a PSAD below 0.20 ng ml −2 was set as the criterion to omit biopsy, nearly 46.3% of patients (463 per 1000) with negative mpMRI could safely avoid unnecessary biopsy, with approximately 4.2% of patients (42 per 1000) at risk of missed diagnosis of PCa and no patients with csPCa missed. A PI-RADS v2 score <3 and a PSAD <0.20 ng ml −2 could be potential criteria for the Chinese population to omit prompt biopsy safely.

BackgroundSeptic myocardial depression has been associated with increased morbidity and mortality. miR-885-5p has been shown to regulate cell growth, senescence, and/or apoptosis. Published studies demonstrated that Homeobox-containing protein 1 (HMBOX1) inhibits inflammatory response, regulates cell autophagy, and apoptosis. However, the role of miR-885-5p/HMBOX1 in sepsis and septic myocardial depression and the underlying mechanism is not fully understood.Materials and MethodsExosomes (exos) derived from sepsis patients (sepsis-exos) were isolated using ultracentrifugation. Rats were subjected to cecal ligation and puncture surgery and treated with sepsis-exos. HMBOX1 was knocked down or overexpressed in AC16 cells using lentiviral plasmids carrying short interfering RNAs targeting human HMBOX1 or carrying HMBOX1 cDNA. Cell pyroptosis was measured by flow cytometry. The secretion of IL-1β and IL-18 was examined by ELISA kits. Quantitative polymerase chain reaction (PCR) or western blot was used for gene expression.ResultsSepsis-exos increased the level of miR-885-5p, decreased HMBOX1, elevated IL-1β and IL-18, and promoted pyroptosis in AC16 cells. Septic rats treated with sepsis-exos increased the serum inflammatory cytokines is associated with increased pyroptosis-related proteins of hearts. MiR-885-5p bound to the three prime untranslated regions of HMBOX1 to negatively regulate its expression. Overexpressing HMBOX1 reversed miR-885-5p-induced elevation of inflammatory cytokines and upregulation of NLRP3, caspase-1, and GSDMD-N in AC16 cells. The mechanistic study indicated that the effect of HMBOX1 was NF-κB dependent.ConclusionSepsis-exos promoted the pyroptosis of AC16 cells through miR-885-5p via HMBOX1. The results show the significance of the miR-885-5p/HMBOX1 axis in myocardial cell pyroptosis and provide new directions for the treatment of septic myocardial depression.

To evaluate the Efficacy and safety of phosphodiesterase type 5 inhibitors as a medical therapy for distal ureteral calculi by means of a systematic review and network meta‐analysis (NMA). We searched the Embase, Medline, and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCTs) published before May, 2017. Stone passage rate as the primary outcome. We used random effects model for pairwise meta‐analyses and Bayesian random effects model for NMA. We evaluated the quality of evidence by the GRADE framework for each network estimate. Five RCTs (861 patients) comparing four different interventions. The results of NMA showed that compared with tamsulosin alone, tamsulosin combined with tadalafil group was associated with significantly higher stone passage rate (odds radio [OR] 2.55, 95% credible intervals [Crl] 1.11 to 5.89). When considering stone expulsion rate, compared with tamsulosin, silodosin was ranked best (OR 3.58, 95% Crl 1.13 to 11.91), followed by tamsulosin combined with tadalafil (OR 2.55, 95% Crl 1.11 to 5.89) and tadalafil alone (OR 1.86, 95% Crl 0.95 to 4.25). No significant difference was found considering safety profiles between any interventions. This meta‐analysis indicates that tamsulosin combined with tadalafil is an effective treatment option for ureteral stones with a low occurrence of side effects. Clinicians should take all known safety and compliance of patients into account when choosing an optimal strategy. Since sample size of included studies, further RCTs are strongly encouraged to address the clinical question.