Exploration of the diagnostic capacity of PSAMR combined with PI-RADS scoring for clinically significant prostate cancer and establishment and validation of the Nomogram prediction model.

PURPOSE: The objective of this investigation was to explore the diagnostic capability of Prostate Specific Antigen Mass Ratio (PSAMR) combined with Prostate Imaging Reporting and Data System (PI-RADS) scoring for clinically significant prostate cancer (CSPC), develop and validate a Nomogram prediction model for the probability of prostate cancer occurrence in patients who have not undergone prostate biopsy. METHODS: Initially, we retrospectively collected clinical and pathological data of patients who underwent trans-perineal prostate puncture at Yijishan Hospital of Wanan Medical College from July 2021 to January 2023. Through logistic univariate and multivariate regression analysis, independent risk factors for CSPC were determined. Receiver Operating Characteristic (ROC) curves were generated to compare the ability of different factors for diagnosis of CSPC. Then, we split the dataset into a training set and validation set, compared their heterogeneity, and developed a Nomogram prediction model based on the training set. Finally, we validated the Nomogram prediction model in terms of discrimination, calibration, and clinical usefulness. RESULTS: Logistic multivariate regression analysis illustrated that age [64-69 (OR = 2.736, P = 0.029); 69-75 (OR = 4.728, P = 0.001); > 75 (OR = 11.344, P < 0.001)], PSAMR [0.44-0.73 (OR = 4.144, P = 0.028); 0.73-1.64(OR = 13.022, P < 0.001); > 1.64(OR = 50.541, P < 0.001)], and PI-RADS score [4 points (OR = 7.780, P < 0.001); 5 points (OR = 24.533, P < 0.001)] were independent risk factors for CSPC. The Area Under the Curve (AUC) of the ROC curves of PSA, PSAMR, PI-RADS score, and PSAMR combined with PI-RADS score were respectively 0.797, 0.874, 0.889, and 0.928. The performance of PSAMR and PI-RADS score for diagnosis of CSPC was superior to PSA, but inferior to PSAMR combined with PI-RADS. Age, PSAMR, and PI-RADS were included in the Nomogram prediction model. The AUCs of the training set ROC curve and the validation set ROC curve were 0.943 (95% CI 0.917-0.970) and 0.878 (95% CI 0.816-0.940), respectively, in the discrimination validation. The calibration curve showed good consistency, and the decision analysis curve suggested the model had good clinical efficacy. CONCLUSIONS: We found that PSAMR combined with PI-RADS scoring had a strong diagnostic capability for CSPC, and provided a Nomogram prediction model to predict the probability of prostate cancer occurrence combined with clinical data.

LncRNA PLAC2 upregulates miR-663 to downregulate TGF-ß1 and suppress bladder cancer cell migration and invasion.

BACKGROUND: The roles of lncRNA PLAC2 in bladder cancer (BC) were explored. METHODS: The expression of PLAC2 in two types of tissue of BC patients was detected by RT-qPCR and the expression data were compared by paired t test. The 56 patients were staged according to the AJCC criteria, and 12, 15, 15 and 14 cases were classified into stage I-IV, respectively. The expression of TGF-ß1 and miR-663 in BC tissues were also detected by RT-qPCR experiments. RESULTS: Our data showed that the expression levels of PLAC2 were significantly lower in BC tissues than that in non-cancer tissues. The expression of PLAC2 was not affect by clinical stages and low expression levels of PLAC2 predicted lower survival rate. The expression of PLAC2 was positively correlated with miR-663 and inversely correlated with TGF-ß1 in BC tissues. In BC cells, downregulated TGF-ß1 and upregulated miR-663 were observed after the overexpression of PLAC2. Overexpression of PLAC2 also resulted in suppressed invasion and migration of BC cells. Overexpression of miR-663 resulted in downregulated TGF-ß1 but did not affect the expression of PLAC2. Overexpression of TGF-ß1 reduced the inhibitory effects of overexpression of PLAC2 and miR-663 on cell migration and invasion. CONCLUSION: PLAC2 can upregulate miR-663 to downregulate TGF-ß1 and suppress BC cell migration and invasion.

Albumin-assisted exfoliated ultrathin rhenium disulfide nanosheets as a tumor targeting and dual-stimuli-responsive drug delivery system for a combination chemo-photothermal treatment.

Herein, we prepared an ultrathin rhenium disulfide nanosheet (utReS2) through the bovine serum albumin (BSA)-assisted ultrasonic exfoliation method, which showed great biocompatibility and high near-infrared (NIR) absorbance. The large surface specific area and the presence of BSA facilitate a high loading ratio and modification of multifunctional molecules. The low solubility anti-cancer drug resveratrol (RSV) was loaded onto the utReS2 surface to form a biocompatible nanocomposite (utReS2@RSV). A targeting molecule, folic acid (FA), was then conjugated to the BSA molecule of utReS2@RSV, resulting in utReS2@RSV-FA. The utReS2@RSV-FA exhibited a photothermal effect under an 808 nm laser irradiation. At pH = 6.5, about 16.5% of the RSV molecules was released from utReS2@RSV-FA over 24 h, while the value reached 55.3% after six cycles of NIR irradiation (5 min, 1 W cm-2). In vitro experiments of utReS2@RSV-FA showed that it had low cytotoxicity and an excellent HepG2 cells targeting effect. Upon pH/temperature dual-stimuli, utReS2@RSV-FA showed an enhanced cytotoxic effect. In vivo experiments of utReS2@RSV-FA intravenously injected into tumor-bearing mice showed that at 24 h post-injection, it could actively target and was largely accumulated in tumor tissue. When the injection was further accompanied by three cycles of NIR irradiation for 5 min, once a day, the tumor was efficiently suppressed, without relapse after 30 days. These findings demonstrate that utReS2@RSV-FA has a remarkable targeting ability while providing a dual-stimuli-responsive drug delivery system, and could effectively be used in a combination chemo-photothermal cancer treatment.

Efficacy and safety of multiple doses of levomilnacipran extended-release for the treatment of major depressive disorder.

OBJECTIVE: The aim of this meta-analysis was to evaluate the efficacy and safety of levomilnacipran extended-release (ER) in the treatment of major depressive disorder (MDD). METHODS: Randomized controlled trials were searched by electronic databases. Unpublished data were also searched by the relevant websites. Weighted mean difference (WMD) and risk ratio (RR) with 95% confidence interval (CI) were calculated and pooled using fixed-effects model or random-effects model. RESULTS: Five randomized placebo-controlled trials including 2,637 patients were analyzed. Compared with placebo, levomilnacipran ER had a greater reduction in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score and Sheehan Disability Scale (SDS) total score (MADRS: WMD -3.49 [95% CI -4.28, -2.70; P<0.00001]; SDS: WMD -2.41 [95% CI -3.05, -1.77; P<0.00001]). Significantly more patients in levomilnacipran ER achieved MADRS response rate (RR 1.35 [95% CI 1.23, 1.47; P<0.00001]) and MADRS remission rate (RR 1.30 [95% CI 1.06, 1.59; P=0.01]). In terms of safety, more patients discontinued due to adverse events (AEs) in levomilnacipran ER compared with placebo (RR 3.15 [95% CI 2.26, 4.39; P<0.00001]), but it was generally well tolerated in each eligible trial. The most common AEs were nausea, delay in ejaculation, erectile dysfunction, tachycardia, headache and increase in heart rate. CONCLUSION: Levomilnacipran ER is a safe and effective short-term treatment for MDD (≤10 weeks). Long-term and head-to-head trials comparing levomilnacipran ER with other antidepressants are needed to confirm the conclusion.