Evidence linking body mass index (BMI) change to prostate cancer risk remains inconsistent despite known associations between adiposity and prostate carcinogenesis.

We conducted a population-based cohort study of 1,332,372 Korean males who completed health examinations in 2009 and 2013 and were followed through 2017. BMI was classified using Asia-Pacific criteria, and changes between 2009 and 2013 defined 25 groups. Prostate cancers were ascertained by ICD-10 (International Classification of Diseases, 10th Revision) codes. Cox proportional hazards models estimated adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) controlling for demographics, lifestyle factors, and comorbidities.

Over 12.7 million person-years, 9,147 prostate cancers were identified. BMI trajectories displayed distinct risk patterns. Remaining underweight (aHR, 0.76; 95% CI, 0.61 to 0.96) or moving from underweight to normal (aHR, 0.65; 95% CI, 0.47 to 0.91) was associated with lower risk, whereas persistent overweight (aHR, 1.18; 95% CI, 1.10 to 1.27), persistent obesity I (aHR, 1.19; 95% CI, 1.12 to 1.27), and transition from overweight to obesity I (aHR, 1.14; 95% CI, 1.03 to 1.27) were associated with higher risk compared with persistent normal BMI. Among males with obesity I, weight loss to normal BMI was associated with reduced risk compared to persistent obesity I (aHR, 0.63; 95% CI, 0.46 to 0.87). Smoking amplified the adverse associations of persistent overweight and obesity. However, persistent obesity II (≥30 kg/m²) was associated with lower risk among males <60 years (aHR, 0.62; 95% CI, 0.44 to 0.89), though this finding should be interpreted with caution as it may reflect detection bias.

The impact of longitudinal adiposity patterns varied by smoking status and age, supporting personalized, lifestage-specific prevention emphasizing weight management and lifestyle modification.

Erectile dysfunction (ED) is a prevalent and distressing consequence of radical prostatectomy (RP) and radiotherapy (RT) for prostate cancer, profoundly impacting quality of life. Despite a wide array of available interventions, their comparative effectiveness remains uncertain in the absence of head-to-head trials.

We conducted a systematic review and network meta-analysis (NMA) of studies evaluating medical interventions for ED following RP or RT. MEDLINE, Embase, and Scopus were searched for eligible studies. Risk of bias (RoB) was assessed using the Cochrane RoB 2 and ROBINS-I tools. A random-effects NMA was performed, with efficacy expressed as odds ratios (ORs) and 95% confidence intervals (CIs). The certainty of evidence was evaluated using the GRADE framework. The primary outcome was recovery of erectile function, assessed using validated measures or the proportion achieving successful intercourse.

Forty-one studies (n=4,157 participants) met inclusion criteria. Following RP, combination therapies were most effective: tadalafil plus intraurethral alprostadil gel (OR 24.8), tadalafil plus vacuum erection device (OR 12.3), and tadalafil plus low-intensity shockwave therapy (OR 8.2) demonstrated the highest odds of functional recovery versus placebo. Following RT, on-demand tadalafil was the most effective intervention (OR 8.0). Pooled analysis of RP studies showed a significant mean improvement in International Index of Erectile Function scores favouring active interventions over control (mean difference 4.5, 95% CI: 2.4-6.5, I²=62%), with longer intervention duration associated with greater improvement. Overall certainty of evidence was low to very low due to RoB, imprecision, and inconsistency.

Combination therapies appear most effective for ED recovery after RP, while on-demand phosphodiesterase type 5 inhibitors are most efficacious after RT. These findings provide novel comparative evidence; however, cautious clinical application and further high-quality research are warranted.

Spatiotemporal control over supramolecular assemblies holds promise for precise theranostics, yet conventional designs often require an extensive modification of the backbone by introducing responsive motifs. Herein, with minimal interference of the molecular backbone, we report a chiral engineering strategy to enhance the pH sensitivity of a tripeptide-drug conjugate (PDC). Specifically, homochiral PDC forms supramolecular nanofibers with a low pH dependence, whereas the heterochiral isomer with alternating D/L residues exhibits a highly pH-dependent self-assembly. Importantly, in carbonic anhydrase IX (CAIX)-overexpressing tumor cells, fibrous assemblies of homochiral PDCs occur at the cell surface, while heterochiral PDCs form nanofibers within lysosomes via protonation. This process subsequently promoted lysosomal membrane permeabilization and enhanced CAIX inhibition, which turns into an efficient way of enhancing cellular Fenton reactions to evoke ferroptosis, thereby improving the antitumor efficacy in breast tumors. Overall, this work proposes a chiral engineering approach for enhancing the pH sensitivity of supramolecular assemblies, which establishes an efficient strategy for spatiotemporal control over supramolecular assemblies and offers alternative insights into the biological effects of heterochirality.

Glioblastoma (GB) is the most aggressive primary malignant brain tumor in adults and remains associated with poor survival despite surgical resection followed by radiotherapy and temozolomide (TMZ) chemotherapy. Intrinsic and acquired resistance to TMZ, including MGMT-dependent DNA repair and activation of pro-survival pathways, could decrease treatment efficacy. Drug repurposing offers an attractive strategy to identify agents that may enhance TMZ activity because these drugs already have known pharmacokinetic and safety profiles. This narrative review summarizes the available evidence on repurposed drugs investigated as potential modulators of TMZ response in GB.

A range of repurposed agents, including chloroquine, valproic acid, levetiracetam, metformin, aspirin, amlodipine, atorvastatin, chlorpromazine, melatonin, disulfiram, bortezomib, and verteporfin, have been evaluated in GB models and selected clinical studies. Reported mechanisms include modulation of MGMT expression, autophagy, oxidative stress, apoptosis, DNA-damage responses, cancer stem-cell properties, and signaling pathways such as PI3K/AKT/mTOR, AMPK, EGFR, STAT3, ERK1/2, and NF-κB. Several agents have enhanced TMZ-associated cytotoxicity in cell culture and animal models. However, clinical evidence remains limited, and the results are inconsistent for some drugs. Blood-brain barrier penetration, achievable intratumoral drug exposure, toxicity, treatment scheduling, and molecular heterogeneity of GB remain major translational challenges.

Repurposed drugs may provide useful candidates for improving TMZ-based therapy in GB. However, most evidence remains preclinical, and further studies are needed to clarify blood-brain barrier penetration, optimal dosing, toxicity, predictive biomarkers, and clinical efficacy. Well-designed prospective clinical trials are required before these combinations can be incorporated into routine GB treatment.

Polycythemia is defined as an elevation of age and sex - adjusted hematocrit. While Polycythemia vera (PV) is a myeloproliferative neoplasm caused by JAK2 mutations leading to an autonomous proliferation of red blood cells. Most cases of polycythemia seen in general practice represent relative polycythemia or are secondary to other causes. Secondary erythrocytosis is most often due to chronic hypoxia, the use of erythropoietin-stimulating drugs such as androgens or SGLT2 inhibitors or erythropoietin -secreting tumors. Relative polycythemia results from chronic plasma volume contraction. Rarely, hereditary erythrocytosis may be a cause of polycythemia. In this review we outline our diagnostic approach to patients with polycythemia, focusing on identifying secondary causes. We suggest that when polycythemia is isolated, secondary and hereditary causes should be considered initially. If polycythemia is accompanied by leukocytosis or thrombocytosis, the initial investigations should be testing for JAK2 mutations and serum erythropoietin levels. Polycythemia vera is characterized by headache, visual disturbances, pruritus, erythromelalgia and splenomegaly. Treatment includes phlebotomy, low-dose aspirin, and cytoreductive agents. In secondary polycythemia, there are no clear guidelines regarding the desired hematocrit and management should be individualized to treat the cause. Phlebotomy is the only modality used to lower the hematocrit when this is required. A systematic clinical approach that prioritizes the exclusion of secondary causes before genetic testing may prevent unnecessary investigations and enable focused, effective patient care.

Acromegaly is a rare disease, due in most of the cases to a growth hormone (GH)-secreting pituitary adenoma (PA), namely neuroendocrine tumour (PitNET). The treatment of patients with acromegaly is multimodal and multi-step, including surgery, medical therapies, and radiotherapy. In the last 30 years, the therapeutic armamentarium for the treatment of acromegaly has progressively increased, and the therapeutic algorithm has been significantly modified through the identification of clinical, biochemical, and molecular biomarkers of treatment outcome. The personalization of acromegaly treatment has shifted the paradigm from a 'trial-and-error' to a 'target-to-treat' treatment approach to achieve early disease control and to reduce the risk of disease-related comorbidities that may lead to an increased mortality. Nevertheless, despite the numerous improvements in the treatment of patients with acromegaly, disease control is not achieved in all patients, according to the results of randomized clinical trials, interventional studies, and prospective and retrospective observational studies. In parallel, the normalization of GH and IGF-I levels may not be sufficient to control acromegaly related symptoms and prevent disease-related comorbidities. In this review, we will report on the most recent aims of treatment and cure in patients with acromegaly, on the efficacy and predictors of response to conventional treatments (such as first- and second-generation somatostatin receptor ligands and growth hormone receptor antagonist). A specific section will focus on the rarer aggressive disease pictures and on the treatment with systemic therapies (such as temozolomide and capecitabine) and on target therapies (such as neo-angiogenesis and immune checkpoint inhibitors).

We reported a rare case in which acute pulmonary thromboembolism (APTE) was the initial clinical manifestation of multiple endocrine neoplasia type 1 (MEN1). A 44-year-old male presented with chest tightness and dyspnea, and was subsequently diagnosed with acute pulmonary embolism on computed tomography pulmonary angiography (CTPA). Medical history revealed a long-standing pituitary adenoma. During the etiologic evaluation, the patient was found to have a hypercalcemic crisis, hyperparathyroidism, and a pancreatic neuroendocrine tumor. Genetic testing confirmed a pathogenic MEN1 mutation (c.1664G>A), which established the diagnosis of MEN1. Along with regular anticoagulation therapy, the patient underwent multidisciplinary evaluation. Oral bromocriptine was continued for the pituitary adenoma, and parathyroidectomy was performed after correction of the hypercalcemic crisis. The pancreatic neuroendocrine tumor is being closely monitored, with elective surgery or somatostatin analogue therapy planned as appropriate to eliminate the underlying cause of pulmonary embolism. Through a brief literature review, we explored how MEN1 may contribute to a hypercoagulable state. The case highlighted the importance of endocrine and genetic screening in patients with unexplained pulmonary embolism.

Prostate cancer (PCa) is one of the most common cancers in males, and its treatment remains challenging due to the tumor microenvironment (TME) with immunosuppressive properties and limited response to anti-PD-1 therapy. Gut microbiota-derived metabolites have recently emerged as modulators of cancer immunometabolism, however, their role in PCa progression and immunotherapy is poorly understood. Here we found that indole-3-lactic acid (ILA), a metabolite produced by Lactobacillus plantarum, exerted dual anti-tumor effects on PCa cells and the TME. Mechanistically, ILA activates the aryl hydrocarbon receptor (AHR), and the resulting AHR/ARNT heterodimer translocates into the nucleus and binds to the promoter of ASF1B. This heterodimer then recruits the HDAC1/2-NuRD complex to reduce H3K27ac levels and suppress ASF1B expression. ASF1B binds to specific residues of ENO1 via its N-terminal core domain and enhances ENO1 enzymatic activity. ILA-induced downregulation of ASF1B impairs this interaction, reduces ENO1 activity, and suppresses the PI3K/Akt pathway, thereby inhibiting the malignant phenotypes of PCa cells. Concurrently, ILA decreased CXCL8 secretion by inhibiting the PI3K/Akt/NF-κB pathway, enhancing CD8⁺ T cell infiltration and M1 macrophage polarization, thereby remodeling the TME. Additionally, ILA synergized with anti-PD-1 therapy to more effectively suppress tumor growth. These findings reveal a novel mechanism by which gut microbiota-derived metabolites regulate PCa progression and immunometabolism, positioning ILA as a potential therapeutic agent to improve PCa treatment.

Robot-assisted surgery has been introduced into several male reproductive diseases, including male infertility-related reconstructive or microsurgical procedures, testicular cancer-related retroperitoneal lymph node dissection, and penile cancer-related inguinal lymph node surgery. However, unlike robot-assisted radical prostatectomy, these non-prostate male reproductive applications remain scattered across small clinical series, technical reports, and procedure-specific reviews. This study mapped the global research landscape and thematic evolution of robot-assisted surgery for male reproductive diseases excluding prostate disease. Publications were retrieved from the Web of Science Core Collection using a disease- and procedure-bound search strategy focused on robot-assisted microsurgery, vasovasostomy, vasoepididymostomy, varicocelectomy, sperm retrieval, azoospermia, testicular cancer/RPLND, and penile cancer/inguinal lymphadenectomy. The search was conducted on June 12, 2026. Articles and reviews in English were retained. Bibliometrix and CiteSpace were used to analyze publication trends, countries, institutions, authors, sources, cited references, keyword co-occurrence, clusters, bursts, and thematic changes. A total of 228 records were initially retrieved. After excluding 67 records outside the retained document types and 8 non-English records, 153 publications were included, comprising 110 articles and 43 reviews. The literature covered 2001-2026, involved 59 sources, 952 authors, 298 author keywords, and 3016 cited references, with an annual growth rate of 6.2%. Annual output remained low before 2013, increased after 2019, and peaked in 2025 (n = 18), whereas 2026 represented partial-year data (n = 9). The United States was the dominant contributor and citation center, while Italy, China, India, England, Germany, Canada, France, Switzerland, and Australia formed the main international network. Keyword analysis identified three principal domains: testicular cancer/RPLND, penile cancer/inguinal lymphadenectomy, and male infertility-related robotic microsurgery. Robot-assisted surgery for male reproductive diseases is a small but expanding field organized around distinct oncologic and reproductive surgery applications. Publication and citation activity is more extensive for testicular cancer/RPLND and penile cancer nodal surgery than for fertility-directed microsurgical reconstruction; however, bibliometric prominence should not be interpreted as greater clinical maturity, quality of evidence, or superiority. Future research should emphasize standardized indications, multicenter outcome reporting, fertility and oncologic endpoints, learning-curve assessment, and cost-effectiveness evaluation.

Esophageal cancer (EC) ranks 11th in incidence and 7th in mortality among malignancies globally. The role of eukaryotic translation initiation factor 6 (eIF6) in esophageal squamous cell carcinoma (ESCA) progression, including its involvement in tumor development, invasion, and epithelial-mesenchymal transition (EMT), remains to be fully characterized.

Bioinformatic and immunohistochemistry (IHC) analyses of 114 ESCA cases demonstrated eIF6 upregulation, which was associated with lower tumor differentiation. Elevated eIF6 expression in ESCA cell lines (KYSE150, TE-1) relative to normal esophageal epithelial cells (HEEC) was verified by reverse transcription-quantitative PCR and western blotting. eIF6 silencing via short hairpin RNA (shRNA) attenuated ESCA cell proliferation, migration, and colony formation in vitro, as assessed by Cell Counting Kit-8, wound healing, and Transwell assays.

Bioinformatic analysis and IHC results showed that eIF6 protein was up-regulated in ESCC, and its expression level was inversely correlated with tumor differentiation degree. eIF6 knockdown was associated with reduced proliferation, migration, and colony formation of ESCC cells, accompanied by shifts in EMT markers, including increased E-cadherin and decreased N-cadherin and Vimentin levels. In addition, eIF6 depletion was accompanied by decreased phosphorylation of AKT (p-AKT^Ser473) and mTOR (p-mTOR), both key components of the PI3K/AKT/mTOR pathway.

These findings indicate an association between eIF6 upregulation and ESCA aggressiveness, along with concomitant changes in the PI3K/AKT/mTOR signaling pathway.