The combination of immune checkpoint inhibitors and antibody-drug conjugates in the treatment of urogenital tumors: a review insights from phase 2 and 3 studies.

With the high incidence of urogenital tumors worldwide, urinary system tumors are among the top 10 most common tumors in men, with prostate cancer ranking first and bladder cancer fourth. Patients with resistant urogenital tumors often have poor prognosis. In recent years, researchers have discovered numerous specific cancer antigens, which has led to the development of several new anti-cancer drugs. Using protein analysis techniques, researchers developed immune checkpoint inhibitors (ICIs) and antibody-conjugated drugs (ADCs) for the treatment of advanced urogenital tumors. However, tumor resistance often leads to the failure of monotherapy. Therefore, clinical trials of the combination of ICIs and ADCs have been carried out in numerous centers around the world. This article reviewed phase 2 and 3 clinical studies of ICIs, ADCs, and their combination in the treatment of urogenital tumors to highlight safe and effective methods for selecting individualized therapeutic strategies for patients. ICIs activate the immune system, whereas ADCs link monoclonal antibodies to toxins, which can achieve a synergistic effect when the two drugs are combined. This synergistic effect provides multiple advantages for the treatment of urogenital tumors.

ROUX-en-Y gastric bypass surgery improves metabolic syndrome-related erectile dysfunction in mice via the IRS-1/PI3K/AKT/eNOS pathway.

Objective: Although many clinical studies have shown that ROUX-en-Y gastric bypass (RYGB) surgery significantly improves metabolic syndrome-related erectile dysfunction (MED), the role and mechanism are unclear. Aim: In this study we used a mouse model to explore how RYGB improves MED induced by a high-fat diet (HFD). Methods: We established a mouse model of metabolic syndrome by feeding an HFD for 16 weeks. The mice were randomly assigned to the standard chow diet (SCD), HFD, or RYGB groups. Body weight, fasting blood glucose, plasma insulin, and total plasma cholesterol were analyzed. Erectile responses were evaluated by determining the mean systolic blood pressure and the intracavernosal pressure (ICP). Penile histologic examination (Masson's trichrome and immunohistochemical stain) and Western blot were performed. Result: Compared with the SCD group, the ICP in the sham group was significantly lower, and the ICP of the RYGB was significantly increased. Masson's trichrome and immunohistochemical staining showed that the content of endothelium and smooth muscle in the corpus cavernosum of mice with MED was significantly reduced. Western blot analysis showed a significant decrease in α-smooth muscle actin and a significant increase in osteopontin in penile tissue in the sham group, which was improved by RYGB surgery. Furthermore, RYGB significantly increased IRS-1/PI3K/Akt/eNOS phosphorylation. Clinical Translation: In this study we explored the mechanism of bariatric surgery to improve erectile dysfunction associated with metabolic syndrome and provided a theoretical basis for clinical research. Strengths and Limitations: First, we did not investigate the mechanism by which RYGB affects the IRS-1/PI3K/Akt/eNOS signaling pathway. Second, the effect of the IRS-1/PI3K/Akt/eNOS signaling pathway on the function of corpus cavernosum endothelial cells and smooth muscle cells remains to be investigated in cellular studies. Conclusion: This study demonstrated that RYGB may not only improve metabolic parameters but also restore erectile function in MED patients. The mechanism of the therapeutic effect of RYGB may be reactivation of the IRS-1/PI3K/Akt/eNOS pathway.

Emerging strategy for the treatment of urothelial carcinoma: Advances in antibody-drug conjugates combination therapy.

Urothelial carcinoma (UC) is a prevalent malignant tumor involving the urinary system. Although there are various treatment modalities, including surgery, chemotherapy, and immune checkpoint inhibitor (ICI) therapy, some patients experience disease recurrence and metastasis with poor prognosis and dismal long-term survival. Antibody-drug conjugates (ADCs), which combine the targeting ability of antibody drugs with the cytotoxicity of chemotherapeutic drugs, have recently emerged as a prominent research focus in the development of individualized precision cancer therapy. Although ADCs have improved the overall response rate in patients with UC, their effectiveness remains limited. Currently, ADC-based combination therapies, particularly ADC combined with ICIs, have demonstrated promising efficacy. This combination approach has advanced the treatment of UC, exhibiting the potential to become the standard first-line therapy for advanced UC in the future. This article reviewed clinical trials involving ADC-based combination therapy for UC and discussed the possible challenges and future perspectives to provide guidance for the clinical treatment of UC.

Based on network pharmacology to explore the effect and mechanism of Yipibushen decoction in improving obese type 2 diabetes mellitus with oligoasthenotspermia.

ETHNOPHARMACOLOGICAL RELEVANCE: A traditional Chinese medicine experience compound known as Yipibushen (YPBS) decoction stimulates qi and nourishes yin, stimulates the kidney and solid essence, dissolves phlegm and eliminates stasis. YPBS decoction has proven to be successful in treating obese type 2 diabetes mellitus with oligoasthenotspermia in clinical settings. Nevertheless, the pharmacological mechanism is not understood. AIM OF THE STUDY: Investigating the mechanism of action of YPBS decoction in enhancing the obese type 2 diabetes mellitus with oligoasthenotspermia involved network pharmacology and animal validation techniques. METHODS AND MATERIALS: The YPBS Decoction' active components were found in the TCMSP database and their targets were identified using UniProtKB. Additionally, targets for the obese type 2 diabetes mellitus with oligoasthenotspermia were found in the GeneCard, DisGeNet, TTD and OMIM databases. The intersection of active ingredients, the obese type 2 diabetes mellitus with oligoasthenotspermia was chosen as the intersection target. The protein-protein interaction (PPI) network of the intersection target was built with the aid of Cytoscape 3.9.1, the core target of PPI was obtained through software analysis in R-project, GO enrichment and KEGG enrichment analysis was carried out on the core target. Finally, animal experiments were used to verify the intersection target. RESULTS: The research revealed 74 intersection targets of YPBS decoction active ingredients in the obese type 2 diabetes mellitus with oligoasthenotspermia. There were also 18 PPI core targets, GO enrichment analysis of PPI core targets involving response to oxidative stress, membrane raft, DNA-binding transcription regulator complex and other biological processes; KEGG involving endocrine resistance, PI3K/AKT signaling pathway, apoptosis and other signal pathways. In the obese type 2 diabetes mellitus with oligoasthenotspermia mice, animal studies have shown that YPBS decoction group could decrease blood glucose levels and improve insulin resistance; improve testicular function, enhance sperm count, sperm motility, sperm viability, and decrease the malformation rate. It could increase the levels of T-SOD and GSH-Px, and decrease the MDA level. In addition to this, it could improve the amount of testosterone hormone, and enhance the expression of PI3K, p-AKT and Bcl-2. CONCLUSION: By controlling the degree of oxidative stress and the PI3K/AKT/Bcl-2 pathway, YPBS decoction may enhance the obese type 2 diabetes mellitus with Oligoasthenotspermia, provide a scientific basis for clinical diagnosis and therapy.

The impact of the COVID-19 pandemic-related quarantine on female sexual behavior: a cross-sectional study in China.

To investigate the impact and factors of home quarantine life on women's sexual lives and behaviors in different areas of China and analyze the prevalence of female sexual dysfunction (FSD) during the COVID-19 pandemic. We surveyed adult women who had a regular sexual life (including regular masturbation) and had been isolated at home for at least one month during the COVID-19 outbreak using online questionnaires. This survey recovered 678 complete questionnaires after screening. According to the findings, the overall score of the Female Sexual Function Inventory (FSFI) during the pandemic was 21.98 ± 6.38, the frequency of FSD was 61.9%, and the frequencies of FSD in Shanghai, Nanjing, and Ningxia were 60.6%, 75.2%, and 52.2%, respectively. The frequency of FSFI scores and other specific items (Desire, Arousal, Lubrication, Orgasm, Satisfaction, and Pain) varied significantly across the three regions (P < 0.05). The overall frequency of FSD in the masturbation population was 34.4%, which was lower than the frequency of FSD in women having paired sexual intercourse (60.1%) (p < 0.05). Further analysis revealed that the occurrence of FSD during the pandemic was related to different age stages, menopause, mode of delivery, level of anxiety and depression, and sexual lifestyles. The COVID-19 pandemic has had a great impact on people's spiritual and sexual lives, which are caused by multiple different variables related to both the individual and the environment. We should emphasize the importance of sexual health in epidemics, and having a harmonious and stable sex life will help us survive the boring life of isolation.

Periurethral and Intravenous Injections of Adipose-Derived Stem Cells to Promote Local Tissue Recovery in a Rat Model of Stress Urinary Incontinence.

OBJECTIVE: To compare the effects of periurethral and intravenous injection of adipose-derived stem cells (ADSCs) on voiding function and tissue recovery in a stress urinary incontinence (SUI) rat model. METHODS: Sixty-four postpartum rats were randomly allocated to a normal group and the SUI model was established in 48 rats by vagina balloon dilation and bilateral ovariectomy. The SUI rats were randomized into 3 groups and received urethral injection of PBS (SUI group), periurethral injection of ADSCs (PU group), and intravenous injection of ADSCs (IV group) in 10 days after the ovariectomy. After 1, 7, and 14 days, ADSCs were tracked in urethra specimen. The urinary function of the remaining rats was analyzed at day 28, and urethral tissues were harvested for Western blotting and histochemical analyses. RESULTS: Alpha smooth muscle actin, myosin heavy chain, vascular endothelial growth factor, and neurofilament protein expression was increased in the IV and PU groups. Voiding function was also improved, with no significant differences between the IV and PU groups. The cell retention rate in rat urethral tissues was higher in the PU group than that in the IV group. Compared with the IV group, myosin heavy chain, vascular endothelial growth factor, neurofilament and transforming growth factor-ß1 (TGF-ß1)/Smad pathway protein expression levels were significantly higher in the PU group, while alpha smooth muscle actin expression was significantly lower (P < .05). CONCLUSION: Periurethral and intravenous injection of ADSCs induces different degrees of recovery of the urethral sphincter, cytokine secretion levels and cell retention rates in the urethral tissues in SUI rats, however, there was no significant difference in 2 methods.

Establishment of Rat Model of Female Genital Sexual Arousal Disorder.

INTRODUCTION: Female Genital Sexual Arousal Disorder (FGSAD) seriously affects women's quality of life and Sexual life, but it still lacks ideal FGSAD animal models for further study. AIM: To establish a specific model of female genital sexual arousal disorder and explore the mechanisms resulting in FGSAD. METHODS: After delivery, female rats were guided by expansions of the vagina and ovariectomy (VD+OVX, n = 10); in VD group female rats were just extended by the vagina (VD, n = 10), in OVX group female rats were treated with ovariectomy (OVX, n = 10);the remaining had 1 longitudinal incision as sham group(n = 10). OUTCOMES: Vaginal dilatation combined with ovariectomy in rats may reflect female genital sexual arousal disorder with high reproducibility and stability. RESULTS: Vaginal tissue of female rats in OVX group and VD+OVX group showed an increase in blood flow, decrease in muscle content compared to the sham group. The proportion of collagen fiber I/III decreased and the elastic fiber showed significant rupture and fragmentation; Structural reticular integrity was also significantly separated and broken from the muscle fibers. However, there was no significant difference in vaginal blood flow, fibers and vascular between VD group and Sham group. The damage of vaginal tissue in VD+OVX group was more significant than that in OVX and VD groups. CLINICAL TRANSLATION: We have constructed a specific animal model that can provide clinical insights into the mechanism of FGSAD and serves as a good avenue for further research of its treatment. STRENGTHS AND LIMITATIONS: Vaginal dilatation combined with ovariectomy in rats is a specific animal model with high reproducibility and stability, but we do acknowledge the shortcomings and limitation present in our study. Since genital arousal disorder has many different etiologies that impact the vagina, the clitoris and surrounding tissues, there is no "gold standard" model that different models attempt to investigate different etiologies. CONCLUSION: The female genital sexual arousal disorder model established by vaginal dilatation combined with ovariectomy is a novel rat model with simple induction conditions, which pathogenic mechanism of female genital sexual arousal disorders maybe connected with the change of VEGF and MMP-9 in vaginal fibromuscular system and microvascular. Li G, Yu P, Hu Y, et al. Establishment of Rat Model of Female Genital Sexual Arousal Disorder. Sex Med 2022;10:100530.