The relationship between metformin and prostate cancer (PCa) remains controversial. To clarify this association, the PubMed, Embase and Cochrane library databases were systematically searched from their inception dates to May 23, 2018, using the keywords “metformin” and “prostate cancer” to identify the related studies. The results included incidence, overall survival (OS), PCa-specific survival (CSS) and recurrence-free survival (RFS), which were measured as hazard ratios (HR) with a 95% confidence interval (95% CI) using Review Manager 5.3 software. A total of 30 cohort studies, including 1,660,795 patients were included in this study. Our study revealed that metformin treatment improves OS, CSS and RFS in PCa (HR = 0.72, 95% CI: 0.59–0.88, P = 0.001; HR = 0.78, 95% CI: 0.64–0.94, P = 0.009; and HR = 0.60, 95% CI: 0.42–0.87 P = 0.006, respectively) compared with non-metformin treatment. However, metformin usage did not reduce the incidence of PCa (HR = 0.86, 95% CI: 0.55–1.34, P = 0.51). In conclusion, compared with non-metformin treatment, metformin therapy can significantly improve OS, CSS and RFS in PCa patients. No association was noted between metformin therapy and PCa incidence. This study indicates a useful direction for the clinical treatment of PCa.

Spider toxins are molecularly diverse and some display not only a strong antibacterial effect but also exhibit significant inhibition of tumor growth and promote tumor cell apoptosis. The aim of the present investigation was to explore different antitumor effects of the spider peptide toxin lycosin-I through different pathways at different concentrations. It was found that by inactivating STAT3 pathway, high concentrations of lycosin-I induce apoptosis in prostate cancer cells and low concentrations of lycosin-I inhibit the migration of prostate cancer cells. This finding provides favorable evidence for further study of the molecular diversity of spider toxins. Impact statement: The spider peptide toxin has become an important research topic. These toxins are molecularly diverse and some display not only a strong antibacterial effect but also exhibit significant inhibition of tumor growth and promote tumor cell apoptosis. Inspired by previous studies, the present study aims to investigate the effects of different concentrations of lycosin-I on the invasiveness and apoptosis of human prostate cancer cells. The findings provide favorable evidence for further study of the molecular diversity of spider toxins.

Mismatch repair-deficient (dMMR) prostate cancer is rare and has not been well studied. We aimed to evaluate the clinical characterization of dMMR metastatic castration-resistant prostate cancer (mCRPC) patients. The MMR genes include MLH1, MLH3, MSH2, MSH6, PMS1, PMS2, and EPCAM, and were analyzed by targeted sequencing of plasma cell-free DNA samples. A total of 109 mCRPC patients were identified, including 50 patients with MMR alterations (pathogenic alterations, n = 7; alterations of unknown significance, n = 43) and 59 patients with wild-type MMR. For the seven patients with pathogenic MMR alterations, the median age at diagnosis was 63.5 years, and 42.9% had a Gleason score ≥8. The median time from androgen deprivation therapy (ADT) initiation to CRPC was 24 months. Compared with the wild-type MMR subgroup, patients with MMR alterations, pathogenic MMR alterations, or MMR alterations of unknown significance showed higher rates of hotspot missense mutations or copy number amplifications in the AR gene (24/50 vs. 10/59, P = 7.8 × 10^–4; 7/7 vs. 10/59, P = 2.5 × 10^–5; 17/43 vs. 10/59, P = 0.013). The presence of any MMR alterations was associated with an inferior response to abiraterone [median progression-free survival (PFS): 5.0 vs. 10.9 months, P = 0.022]. Shorter PFS times were observed in both the pathogenic MMR alteration subgroup (median PFS: 5 months) and the MMR alterations of unknown significance subgroup (median PFS: 5.3 months), compared with the PFS of those with wild-type MMR genes (median PFS: 10.9 months, P = 0.052). There was no statistically significant difference in response to docetaxel chemotherapy between the MMR alterations of unknown significance and the wild-type MMR subgroups (median PFS: 8.2 vs. 8.1 months, P = 0.23). Our results demonstrate that dMMR mCRPC patients have an equivalent response to standard ADT and taxane-based chemotherapy treatments compared with wild-type MMR patients. Patients with both pathogenic and unknown significance alterations of MMR genes had poorer responses to abiraterone therapy.

Background: Imaging techniques that quantitatively and automatically measure changes in the myocardial microcirculation in patients with diabetes are lacking.Purpose: To detect diabetic myocardial microvascular complications using a novel automatic quantitative perfusion MRI technique, and to explore the relationship between myocardial microcirculation dysfunction and fibrosis.Study Type: Prospective.Subjects: 101 patients with type 2 diabetes mellitus (T2DM) (53 without and 48 with complications), 20 healthy volunteers.Field Strength/Sequence: 3.0T; modified Look‐Locker inversion‐recovery sequence; saturation recovery sequence and dual‐bolus technique; segmented fast low‐angle shot sequence.Assessment: All participants underwent MRI to determine the rest myocardial blood flow (MBF), stress MBF, myocardial perfusion reserve (MPR), and extracellular volume (ECV), which represents the extent of myocardial fibrosis.Statistical Tests: Kolmogorov–Smirnov test, Shapiro–Wilk test, Kruskal–Wallis H test, Mann–Whitney U test, chi‐square test, Spearman correlation coefficient, multivariable linear regression analysis. P < 0.05 was considered statistically significant.Results: The rest MBF was not significantly different between the T2DM without complications group (1.1, IQR: 0.9–1.3) and the control group (1.1, 1.0–1.3) (P = 1.000), but it was significantly lower in the T2DM with complications group (0.8, 0.6–1.0) than in both other groups. The stress MBF and MPR were significantly lower in the T2DM without complications group (1.9, 1.5–2.3, and 1.7, 1.4–2.1, respectively) than in the control group (3.0, 2.6–3.5, and 2.7, 2.4–3.1, respectively), and were also significantly lower in the T2DM with complications group (1.1, 0.9–1.4, and 1.4, 1.2–1.8, respectively) than in the T2DM without complications group. A decrease in MBF and MPR were significantly associated with an increase in the ECV.Data Conclusion: Quantitative perfusion MRI can evaluate myocardial microcirculation dysfunction. In T2DM, there was a significant decrease in both MBF and MPR compared to healthy controls, with the decrease being significantly different between T2DM with and without complications groups. The decrease of MBF was significantly associated with the development of myocardial fibrosis, as determined by ECV.Level of Evidence: 2Technical Efficacy: Stage 3

Introduction: To investigate age-specific characteristics of adrenal tumors in older adults and to identify predictors for adrenal malignancy. Methods: Inpatients ≥60 years old with adrenal tumor evaluated at a large medical center between January 2011 and December 2023 were retrospectively enrolled. Results: Of 2,633 inpatients with adrenal tumor, 559 (21.2%, ≥60 years) were eligible for analysis, 52.8% were men, with a median age of 64 years. 58.7% patients were incidentally diagnosed. The median tumor size was 29 mm, and the median unenhanced computed tomographic (CT) attenuation was 15.0 Hounsfield units (HU). Older patients presented a relatively high prevalence of malignant adrenal tumors, accounting for 19.0% of all cases. Adrenal metastases were the most common malignant adrenal tumors, accounting for 59.4% of all malignant cases. A risk model was conducted to predict adrenal malignancy, and the area under the curve was 0.89. Predictors included incidental discovery, male, bilateral tumor, older age, higher HU, and lower weight. The optimal cutoff value was age=67.5 years, size=42.5 mm and CT attenuation=20.5 HU, respectively. Conclusions: Older patients presented the age-specific spectrum of diagnosis, in particular a high prevalence of adrenal metastases. Certain predictors may help to differentiate a malignant lesion from a benign one. This study helps to expand the current knowledge of the adrenal tumor in older adults and inspire robust therapies with better outcomes.

Background: Primary aldosteronism (PA) is associated with adverse cardiovascular outcomes. Elevated aldosterone levels in PA contribute to cardiac remodeling. This study aimed to apply cardiac magnetic resonance imaging (MRI) to longitudinally compare cardiac remodeling changes before and after targeted therapy between patients with PA and those with essential hypertension (EH) and to identify independent clinical predictors of left ventricular remodeling. Methods: We studied 75 consecutive patients with PA and 75 with EH. Patients with PA were treated with surgery, while patients with EH received pharmacotherapy. Clinical characteristics and MRI findings were collected at baseline and 6 months after treatment. Generalized estimating equations were applied to compare the changes in MRI variables. The relationship between the left ventricular remodeling parameters and physiological variables was analyzed via linear regression. Results: Median left ventricular mass {PA: 97 [interquartile range (IQR), 85–109] g; EH: 87 (IQR, 76–102) g; P=0.015} and mass index [PA: 54.40 (IQR, 47.22–65.22) g/m²; EH: 50.54 (IQR, 41.95–61.83) g/m²; P=0.009] were higher in the patients with PA than in those with EH, while the median myocardial perfusion reserve (MPR) [PA: 1.9 (IQR, 1.8–1.9); EH: 2.3 (IQR, 2.1–2.4); P<0.001] was lower. Both groups exhibited significant reductions in left ventricular mass, improvements in MPR, and decreases in extracellular volume (ECV) fraction following treatment. These changes were more pronounced in patients with PA than in those with the EH. Multivariate analysis showed that the baseline log plasma aldosterone-to-renin ratio (ARR) was an independent predictor of left ventricular mass, mass index, MPR, and ECV fraction, with beta values of 0.640, 0.658, –0.711, and 0.503, respectively. Conclusions: Patients with PA and those with EH demonstrated improvements in ventricular remodeling posttreatment, with the former exhibiting a more substantial degree of recovery. LogARR was an independent predictor of left ventricular remodeling.