Diabetes mellitus (DM) is a chronic metabolic disease that often leads to vascular endothelial injury and peripheral neuropathy. Erectile dysfunction (ED), a common condition in andrology, is frequently associated with DM. The incidence of diabetes mellitus-induced ED (DMED) is second only to the cardiovascular complications of diabetes. Compared to other types of ED, DMED presents with more severe symptoms, rapid progression, and notable resistance to phosphodiesterase type 5 inhibitors (PDE5is). Various forms of programmed cell death (PCD)—including apoptosis, autophagy, pyroptosis, and ferroptosis—play pivotal roles in the pathogenesis of DMED. An exacerbation of DMED is linked to critical irritants like advanced glycation end-products (AGEs) and reactive oxygen species (ROS) in the corpus cavernosum tissue. These irritants can spark anomalous activations of diverse PCDs, which damage primary corpus cavernosum cells like cavernous nerve cells, endothelial cells, and myocytes, leading to ED. Hence, we reviewed current knowledge on the mechanisms and therapeutic potential of targeting PCDs in DMED, aiming to advance strategies for enhancing erectile function.

Kidney renal clear cell carcinoma (KIRC) is a heterogeneous malignant tumor with high incidence, metastasis, and mortality. The imbalance of copper homeostasis can produce cytotoxicity and cause cell damage. At the same time, copper can also induce tumor cell death and inhibit tumor transformation. The latest research found that this copper-induced cell death is different from the known cell death pathway, so it is defined as cuproptosis. We included 539 KIRC samples and 72 normal tissues from the Cancer Genome Atlas (TCGA) in our study. After identifying long non-coding RNAs (lncRNAs) significantly associated with cuproptosis, we clustered 526 KIRC samples based on the prognostic lncRNAs and obtained two different patterns (Cuproptosis.C1 and C2). C1 indicated an obviously worse prognostic outcome and possessed a higher immune score and immune cell infiltration level. Moreover, a prognosis signature (CRGscore) was constructed to effectively and accurately evaluate the overall survival (OS) of KIRC patients. There were significant differences in tumor immune microenvironment (TIME) and tumor mutation burden (TMB) between CRGscore-defined groups. CRGscore also has the potential to predict medicine efficacy.

Original Article Positive and non-linear association of sagittal abdominal diameter-to-height ratio with stress urinary incontinence in US women: evidence from NHANES 2011–2016 Jun Zhang, Sheng Xin, Jiaquan Mao, Adilijiang Aibibuli, Yang Luan, Tao Wang, Wen Song, Xiaodong Song

To investigate the relationship between android-to-gynoid fat ratio (A/G ratio) and stress urinary incontinence (SUI) in US adult women. The study employed data from the National Health and Nutrition Examination Survey (NHANES) database, encompassing the 2005–2006 and 2011–2018 cycles. We utilized multivariable-adjusted logistic regression models to examine the independent effect of the A/G ratio on SUI. Additionally, refined subgroup analyses were conducted to assess the impact of effect modifiers, along with sophisticated smooth curve fitting methods to delve into the potential non-linear relationship between the A/G ratio and SUI. Of the 6779 women participants with an average age of 40.812, 2565 (37.8%) self-reported SUI. A non-linear relationship between the A/G ratio and SUI has been detected, with the threshold (A/G ratio = 0.446). Above and below this threshold, the effect sizes and the 95% confidence intervals were 1.464 (0.775–2.766) and 10.308 (3.558–29.863), respectively. Subgroup analyses showed that the positive association was more pronounced among young women who were premenopausal, living alone, hypertensive and with normal or low body mass index (BMI). There was a non-linear relationship between the A/G ratio and SUI. In individuals with a lower A/G ratio, even small increases in the A/G ratio substantially elevated the risk of SUI. Results of this study indicate that A/G ratio, as a measure of fat distribution, is of great importance for clinicians in assessing SUI risk and timely intervening.

Background/Objectives: Diabetes mellitus-induced erectile dysfunction (DMED) is characterized by severe endothelial and smooth-muscle dysfunction and reduced responsiveness to conventional therapy. Guanxinning tablet (GXN), a traditional Chinese medicine compound containing Salvia miltiorrhiza (Danshen) and Ligusticum stratum (Chuanxiong), has vascular-protective and anti-oxidative properties, but its effect on DMED remains unclear. This study evaluated whether GXN improves erectile function in a streptozotocin (STZ)-induced type 1 diabetic rat model and explored the possible involvement of PI3K/Akt/FOXO1 signaling. Methods: STZ-induced diabetic rats with ED were treated with GXN. Artery pressure (AP) and intracavernous pressure (ICP) were measured to evaluate erectile dysfunction. Western blots, immunohistochemistry, immunofluorescence, biochemical assays, TUNEL staining, RNA-seq, and in vitro HCMEC assays were performed to evaluate erectile effector cell function, oxidative stress, fibrosis, apoptosis, and PI3K/Akt/FOXO1-associated changes. Results: GXN improved erectile function in DMED rats and was associated with improved endothelial and smooth-muscle-related markers, reduced oxidative stress, attenuated fibrosis, and decreased apoptosis. RNA-seq and protein validation suggested that GXN treatment was associated with activation of PI3K/Akt/FOXO1-related signaling. In HCMECs, LY294002 (a PI3K inhibitor) partially reversed the GXN-associated improvement in cell viability and apoptosis-related markers. Conclusions: GXN ameliorated erectile dysfunction and tissue injury in STZ-induced type 1 diabetic rats, which were associated with PI3K/Akt/FOXO1 signaling. These findings support the potential of GXN as a traditional Chinese medicine compound for treating DMED.