Prostate cancer represents a prevalent malignancy within the male genitourinary system. In recent years, its incidence in China has gradually increased, becoming a significant public health issue. While early detection correlates strongly with improved prognosis, the majority of newly diagnosed prostate cancer patients in China are already in intermediate or advanced stages, precluding curative-intent interventions and contributing to marked survival disparities. The progression of prostate cancer is lengthy, typically encompassing diagnosis, treatment, progression, metastasis, and death, accompanied by a decline in quality of life. Personalized treatment plans should be developed based on the disease stage and patient preferences. In non-metastatic prostate cancer, where the tumor is confined to the prostate, surgery and radiotherapy are the primary treatments, supplemented by neoadjuvant and adjuvant therapies to delay metastasis. For metastatic prostate cancer, systemic therapy is prioritized to prolong survival. In metastatic hormone-sensitive prostate cancer, controlling androgen levels is crucial, while treatment options for metastatic castration resistant prostate cancer are relatively limited, necessitating individualized and precise treatment. During prostate cancer management, prostate-specific antigen levels are closely linked to prognosis and require monitoring. Bone metastasis, the most common site in prostate cancer patients, often triggers skeletal-related events, demanding effective prevention and management. Treatment-related adverse reactions are also a clinical challenge, requiring balanced risk-benefit assessments and judicious drug selection to preserve quality of life. Rapid advancements in screening technologies, surgical innovations, drug development, and China-specific epidemiological factors further complicate decision-making in holistic prostate cancer management. To optimize the standardization of prostate cancer diagnosis and treatment in China, the Genitourinary Oncology Committee of Chinese Anti-cancer Association synthesized global guidelines, clinical evidence and clinical expertise, and addressed critical challenges in the whole-course management of prostate cancer to formulate a multidisciplinary consensus. The expert consensus on whole-course management of prostate cancer (2025 edition) establishes standardized protocols to guide clinical practice, improve treatment outcomes, and enhance patient quality of life.
Humans ; Male ; Prostatic Neoplasms/diagnosis* ; Consensus ; Prostate-Specific Antigen/blood* ; Quality of Life ; Prostatic Neoplasms, Castration-Resistant/pathology* ; China ; Bone Neoplasms/secondary* ; Androgen Antagonists/therapeutic use*

BACKGROUND: Angiotensin receptor neprilysin inhibitors (ARNIs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers (BBs), and mineralocorticoid receptor antagonists (MRAs) are the cornerstones in treating heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter 2 inhibitors (SGLT-2is) are included in HFrEF treatment guidelines. However, the effect of SGLT-2i and the five drugs on HFrEF have not yet been systematically evaluated. METHODS: PubMed, Embase, and the Cochrane Library were searched for randomized controlled trials (RCTs) from inception dates to September 23, 2022. Additional trials from previous relevant reviews and references were also included. The primary outcomes were changes in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter/dimension (LVEDD), left ventricular end-systolic diameter/dimension (LVESD), left ventricular end-diastolic volume (LVEDV), and left ventricular end-systolic volume (LVESV), left ventricular end-systolic volume index (LVESVI), and left ventricular end-diastolic volume index (LVEDVI). Secondary outcomes were New York Heart Association (NYHA) class, 6-min walking distance (6MWD), B-type natriuretic peptide (BNP) level, and N-terminal pro-BNP (NT-proBNP) level. The effect sizes were presented as the mean difference (MD) with 95% confidence interval (CI). RESULTS: We included 68 RCTs involving 16,425 patients. Compared with placebo, ARNI + BB + MRA + SGLT-2i was the most effective combination to improve LVEF (15.63%, 95% CI: 9.91% to 21.68%). ARNI + BB + MRA + SGLT-2i (5.83%, 95% CI: 0.53% to 11.14%) and ARNI + BB + MRA (3.83%, 95% CI: 0.72% to 6.90%) were superior to the traditional golden triangle ACEI + BB + MRA in improving LVEF. ACEI + BB + MRA + SGLT-2i was better than ACEI + BB + MRA (-8.05 mL/m 2 , 95% CI: -14.88 to -1.23 mL/m 2 ) and ACEI + BB + SGLT-2i (-18.94 mL/m 2 , 95% CI: -36.97 to -0.61 mL/m 2 ) in improving LVEDVI. ACEI + BB + MRA + SGLT-2i (-3254.21 pg/mL, 95% CI: -6242.19 to -560.47 pg/mL) was superior to ARB + BB + MRA in reducing NT-proBNP. CONCLUSIONS: Adding SGLT-2i to ARNI/ACEI + BB + MRA is beneficial for reversing cardiac remodeling. The new quadruple drug "ARNI + BB + MRA + SGLT-2i" is superior to the golden triangle "ACEI + BB + MRA" in improving LVEF. REGISTRATION PROSPERO; No. CRD42022354792.
Humans ; Heart Failure/physiopathology* ; Stroke Volume/physiology* ; Angiotensin Receptor Antagonists/therapeutic use* ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use* ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use* ; Randomized Controlled Trials as Topic ; Mineralocorticoid Receptor Antagonists/therapeutic use* ; Adrenergic beta-Antagonists/therapeutic use*

Androgens play an important role in prostate cancer development and progression. Androgen action is mediated through the androgen receptor (AR), a ligand-dependent DNA-binding transcription factor. AR is arguably the most important target for prostate cancer treatment. Current USA Food and Drug Administration (FDA)-approved AR inhibitors target the ligand-binding domain (LBD) and have exhibited efficacy in prostate cancer patients, particularly when used in combination with androgen deprivation therapy. Unfortunately, patients treated with the currently approved AR-targeting agents develop resistance and relapse with castration-resistant prostate cancer (CRPC). The major mechanism leading to CRPC involves reactivation of AR signaling mainly through AR gene amplification, mutation, and/or splice variants. To effectively inhibit the reactivated AR signaling, new approaches to target AR are being actively explored. These new approaches include novel small molecule inhibitors targeting various domains of AR and agents that can degrade AR. The present review provides a summary of the existing FDA-approved AR antagonists and the current development of some of the AR targeting agents.
Humans ; Male ; Androgen Receptor Antagonists/therapeutic use* ; Receptors, Androgen/metabolism* ; Prostatic Neoplasms/drug therapy* ; Prostatic Neoplasms, Castration-Resistant/drug therapy* ; Signal Transduction/drug effects*

Androgen deprivation therapy (ADT) can negatively affect sexual function, and only a minority of patients report sexual activity. We reviewed the existing literature regarding the proportion of men who remained sexually active during and after ADT. The PubMed database was searched for studies published over the past 20 years. We selected and reviewed randomized clinical trials that provided sexual function data at baseline and during and after ADT. The primary outcome measure was the sexual function. Studies assessed sexual function using quality of life patient-reported outcome measures, which included sexual potency/activity evaluation. Information from 2947 patients was analyzed in this review. The median age of patients was 70 years. At baseline, a median of 49.9% (95% confidence interval [CI]: 49.1%-50.7%) of the patients reported being sexually active. At 6 months, 12 months, and 2 years or later of ADT treatment, a median of 10.3% (95% CI: 10.2%-10.5%), 8.9% (95% CI: 8.6%-9.2%), and 8.3% (95% CI: 8.2%-8.5%) of the patients reported being sexually active, respectively. Considering that half of the patients were sexually active at baseline, it seems probable that more than 10% of the patients who were sexually active before starting ADT remained sexually active when undergoing ADT. In conclusion, despite the common belief that ADT eliminates sexual activity, this analysis found that approximately 1 in 10 men are sexually active when on ADT, and this proportion is likely increased in men who are sexually active before starting ADT. Attention to sexual activity should not be dismissed in men on ADT.
Humans ; Male ; Prostatic Neoplasms/drug therapy* ; Androgen Antagonists/therapeutic use* ; Sexual Behavior/drug effects* ; Quality of Life ; Aged

Early-life stress (ES) leads to cognitive dysfunction in female adolescents, but the underlying neural mechanisms remain elusive. Recent evidence suggests that the cell adhesion molecules NECTIN1 and NECTIN3 play a role in cognition and ES-related cognitive deficits in male rodents. In this study, we aimed to investigate whether and how nectins contribute to ES-induced cognitive dysfunction in female adolescents. Applying the well-established limited bedding and nesting material paradigm, we found that ES impairs recognition memory, suppresses prefrontal NECTIN1 and hippocampal NECTIN3 expression, and upregulates corticotropin-releasing hormone (Crh) and its receptor 1 (Crhr1) mRNA levels in the hippocampus of adolescent female mice. Genetic experiments revealed that the reduction of dorsal CA1 (dCA1) NECTIN3 mediates ES-induced object recognition memory deficits, as knocking down dCA1 NECTIN3 impaired animals' performance in the novel object recognition task, while overexpression of dCA1 NECTIN3 successfully reversed the ES-induced deficits. Notably, prefrontal NECTIN1 knockdown did not result in significant cognitive impairments. Furthermore, acute systemic administration of antalarmin, a CRHR1 antagonist, upregulated hippocampal NECTIN3 levels and rescued object and spatial memory deficits in stressed mice. Our findings underscore the critical role of dCA1 NECTIN3 in mediating ES-induced object recognition memory deficits in adolescent female mice, highlighting it as a potential therapeutic target for stress-related psychiatric disorders in women.
Animals ; Female ; Mice ; CA1 Region, Hippocampal/metabolism* ; Cell Adhesion Molecules/metabolism* ; CRF Receptor, Type 1/metabolism* ; Memory Disorders/etiology* ; Mice, Inbred C57BL ; Nectins/genetics* ; Receptors, Corticotropin-Releasing Hormone/antagonists & inhibitors* ; Recognition, Psychology/physiology* ; Stress, Psychological/complications*

Polycystic ovary syndrome (PCOS) is the predominant cause of subfertility in reproductive-aged women; however, its pathophysiology remains unknown. Neurotensin (NTS) is a member of the gut-brain peptide family and is involved in ovulation; its relationship with PCOS is unclear. Here, we found that NTS expression in ovarian granulosa cells and follicular fluids was markedly decreased in patients with PCOS. In the in vitro culture of cumulus-oocyte complexes, the neurotensin receptor 1 (NTSR1) antagonist SR48692 blocked cumulus expansion and oocyte meiotic maturation by inhibiting metabolic cooperation and damaging the mitochondrial structure in oocytes and surrounding cumulus cells. Furthermore, the ERK1/2-early growth response 1 pathway was found to be a key downstream mediator of NTS/NTSR1 in the ovulatory process. Animal studies showed that in vivo injection of SR48692 in mice reduced ovulation efficiency and contributed to irregular estrus cycles and polycystic ovary morphology. By contrast, NTS partially ameliorated the ovarian abnormalities in mice with dehydroepiandrosterone-induced PCOS. Our findings highlighted the critical role of NTS reduction and consequent abnormal NTSR1 signaling in the ovulatory dysfunction of PCOS, suggesting a potential strategy for PCOS treatment.
Polycystic Ovary Syndrome/physiopathology* ; Female ; Animals ; Neurotensin/metabolism* ; Receptors, Neurotensin/antagonists & inhibitors* ; Mice ; Ovulation/drug effects* ; Humans ; Granulosa Cells/metabolism* ; Adult ; Oocytes/metabolism* ; MAP Kinase Signaling System ; Signal Transduction ; Follicular Fluid/metabolism* ; Disease Models, Animal ; Gonadotropin-Releasing Hormone/analogs & derivatives*

INTRODUCTION: We investigated the factors associated with readmission in patients with congestive heart failure (HF) receiving long-term administration of tolvaptan (TLV) to support treatment decisions for HF. METHODS: This retrospective cohort study included 181 patients with congestive HF who received long-term administration of TLV. Long-term administration of TLV was defined as the administration of TLV for 60 days or longer. The outcome was a readmission event for worsening HF within 1 year after discharge. Significant factors associated with readmission were selected using multivariate analysis. To compare the time to readmission using significant factors extracted in a multivariate analysis, readmission curves were constructed using the Kaplan-Meier method and analysed using the log-rank test. RESULTS: The median age was 78 years (range, 38-96 years), 117 patients (64.6%) were males, and 77 patients (42.5%) had a hospitalisation history of HF. Readmission for worsening HF within 1 year after long-term TLV treatment occurred in 62 patients (34.3%). In the multivariate analysis, estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m 2 (odds ratio, 3.22; 95% confidence interval, 1.661-6.249; P = 0.001) was an independent significant factor. When eGFR at discharge was divided into two groups (eGFR < 30 vs. eGFR ≥ 30), readmission rates within 1 year were 53.3% vs. 25.4%, respectively ( P = 0.001). CONCLUSION We revealed that eGFR was strongly associated with readmission in patients with HF who received long-term administration of TLV. Furthermore, we showed that eGFR is an important indicator in guiding treatment of HF in patients receiving TLV.
Humans ; Tolvaptan/therapeutic use* ; Heart Failure/drug therapy* ; Male ; Female ; Patient Readmission/statistics & numerical data* ; Aged ; Retrospective Studies ; Aged, 80 and over ; Middle Aged ; Glomerular Filtration Rate ; Adult ; Antidiuretic Hormone Receptor Antagonists/therapeutic use* ; Risk Factors ; Kaplan-Meier Estimate ; Multivariate Analysis

Arginine vasopressin (AVP) plays a crucial role in various physiological processes including water reabsorption, cardiovascular homeostasis, hormone secretion, and social behavior. AVP acts through three distinct receptor subtypes, i.e., V1a, V1b, and V2. Among them, the vasopressin V2 receptor (V2R) was initially discovered in the principal cells of renal collecting ducts, where it is primarily involved in regulating water reabsorption. However, in recent years, with the advancement of imaging and bioinformatics techniques, there has been a deeper understanding of the microstructure, protein binding capacity, and specific tissue distribution of V2R. Additionally, the pathogenic roles and target effects of V2R in various diseases have been uncovered through ectopic overexpression, activation, or antagonism. This paper aims to provide a brief overview of current research status on the physiological functions, pathophysiological mechanisms, and drug development related to V2R in recent years.
Receptors, Vasopressin/physiology* ; Humans ; Animals ; Antidiuretic Hormone Receptor Antagonists ; Arginine Vasopressin/physiology*

The final analysis of the phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) trial showed improvement in overall survival (OS) and other efficacy endpoints with apalutamide plus androgen deprivation therapy (ADT) versus ADT alone in patients with metastatic castration-sensitive prostate cancer (mCSPC). As ethnicity and regional differences may affect treatment outcomes in advanced prostate cancer, a post hoc final analysis was conducted to assess the efficacy and safety of apalutamide in the Asian subpopulation. Event-driven endpoints were OS, and time from randomization to initiation of castration resistance, prostate-specific antigen (PSA) progression, and second progression-free survival (PFS2) on first subsequent therapy or death. Efficacy endpoints were assessed using the Kaplan-Meier method and Cox proportional-hazards models without formal statistical testing and adjustment for multiplicity. Participating Asian patients received once-daily apalutamide 240 mg ( n = 111) or placebo ( n = 110) plus ADT. After a median follow-up of 42.5 months and despite crossover of 47 placebo recipients to open-label apalutamide, apalutamide reduced the risk of death by 32% (hazard ratio [HR]: 0.68; 95% confidence interval [CI]: 0.42-1.13), risk of castration resistance by 69% (HR: 0.31; 95% CI: 0.21-0.46), PSA progression by 79% (HR: 0.21; 95% CI: 0.13-0.35) and PFS2 by 24% (HR: 0.76; 95% CI: 0.44-1.29) relative to placebo. The outcomes were comparable between subgroups with low- and high-volume disease at baseline. No new safety issues were identified. Apalutamide provides valuable clinical benefits to Asian patients with mCSPC, with an efficacy and safety profile consistent with that in the overall patient population.
Male ; Humans ; Prostatic Neoplasms/pathology* ; Androgen Antagonists/therapeutic use* ; Prostate-Specific Antigen ; Castration ; Prostatic Neoplasms, Castration-Resistant/drug therapy*

Neurological diseases include a variety of neurodegenerative diseases and other brain damage diseases.The treatment schemes for neurological diseases are still in research.The existing clinical and basic studies have confirmed that traditional estrogen therapy has certain protective effect on the nervous system,while it increases the risk of breast or endometrial cancer.The emergence of the selective estrogen receptor modulators (SERMs) can avoid the above mentioned problems.The available studies have confirmed the protective effect of tamoxifen as a SERM on the nervous system.This paper reviews the role and functioning mechanisms of tamoxifen in the nervous system and cognitive function,aiming to provide guidance for the future application of tamoxifen in the treatment of neurological diseases and the improvement of cognitive function.
Tamoxifen/therapeutic use* ; Selective Estrogen Receptor Modulators/therapeutic use* ; Cognition ; Nervous System