Hengjun Xiao

Introduction: Prostate cancer (PCa) is a common malignancy of the male genitourinary system with high metastatic potential and poor clinical outcomes, for which effective biomarkers and therapeutic targets remain limited. Methods: This study employed a multi-omics approach, integrating transcriptome profiles, age-related gene screening, and machine learning techniques, to analyze four GEO datasets, in order to identify key diagnostic biomarkers for prostate cancer (PCa). Results: Differentially expressed aging-related genes were identified, with enrichment analyses revealing significant involvement in PCa. Using machine learning algorithms, a robust diagnostic model centered on GSTP1 was developed, demonstrating high predictive performance. GSTP1 depletion drove multiple oncogenic phenotypes, including enhanced proliferation, migration, invasion, and the inhibition of cellular aging and DNA damage, suggesting that GSTP1 may promote cellular senescence while restraining malignant progression. Furthermore, its expression correlated with distinct immunocyte profiles, highlighting a role in shaping the PCa immune landscape. Discussion: Our findings confirm that GSTP1 functions as an aging-associated stress response gene, offering new perspectives on prostate cancer pathogenesis and showing promise for advancing therapeutic strategies that target both aging and immune associations. This study provides a comprehensive framework for leveraging aging biomarkers in precision oncology and highlights GSTP1 as a promising candidate for clinical translation in PCa management.

Kidney allograft rejection exhibits highly complex features due to the intricate immune mechanisms involved. The early and accurate diagnosis of rejection remains challenging, particularly when differentiating between/among subtypes. Herein, the authors present "RenalTransPredNet," an interpretable model that integrates whole-slide images with routine clinicopathological variables to diagnose kidney allograft rejection. This study included kidney allograft biopsies performed at the Headquarters and Lingnan Hospital of the Third Affiliated Hospital of Sun Yat-sen University between January 2015 and August 2024. After screening, 1086 digital whole-slide images from 362 biopsies and their corresponding clinicopathological information were analyzed, comprising 209 other lesions and 153 rejections. By integrating multiple instance learning-based pathological image analysis with random forest-based clinicopathological information analysis, RenalTransPredNet was used to efficiently construct models for kidney allograft rejection-related multiclass and binary classification tasks. RenalTransPredNet achieved a higher area under the curve (AUC) value than both the pathological imaging and clinicopathological information models in detecting and subtyping kidney allograft rejection, yielding an AUC of 0.886 using data from the internal testing set. For the prediction of treatment response to rejection, RenalTransPredNet yielded an AUC of 0.743. In the task predicting graft loss after rejection, RenalTransPredNet demonstrated predictive capabilities for graft loss at 1, 2, 3, and 5 years post-rejection, with AUCs of 0.876, 0.942, 0.904, and 0.978, respectively. These findings support the potential of RenalTransPredNet in improving the diagnostic accuracy of pathologists in detecting and subtyping kidney allograft rejection and in contributing to prognostic assessments.

Background: The use of hepatitis B virus (HBV)-positive donor kidneys to expand the donor pool has been implemented, but limited evidence exists regarding their impact on transplant outcomes. This study aimed to investigate the effects of donor HBV infection on transplant outcomes. Methods: Donor and recipient data between 2015 and 2021 were collected. A total of 743 kidney transplant cases were screened, including 94 donor hepatitis B surface antigen (HBsAg)+/recipient HBsAg– (D+R–) and 649 donor HBsAg–/recipient HBsAg– (D–R–) cases. The analysis endpoints included recipient HBV infection, delayed graft function (DGF), peak estimated glomerular filtration rate (eGFR) within 12 months, recipient survival, and death-censored graft survival (DCGS). Results: The D+R– group had a significantly higher risk of HBV infection compared to the D–R– group (6/72 vs. 3/231; relative risk, 6.4; p = 0.007). The risk of HBV transmission decreased significantly with increasing hepatitis B surface antibody (HBsAb) titer (p for trend = 0.003). Furthermore, the D+R– group did not exhibit an increased risk of DGF compared to the D–R– group (odds ratio, 0.70; p = 0.51) in the multivariable mixed model. Both groups had similar peak eGFR within 12 months (β = 1.01, p = 0.71), and this had no impact on patient survival (hazard ratio [HR], 0.36; p = 0.10) and DCGS (HR, 0.79, p = 0.59) in the shared-frailty Cox model. Conclusion: The use of HBsAg-positive donor kidneys appears relatively safe for HBV-immunized recipients in the short term. D+R– does not negatively affect graft function recovery and provides comparable posttransplant outcomes. Maintaining an HBsAb titer over 100 mIU/mL before transplantation is critical to reduce the risk of HBV transmission.

Introduction: Circulating tumor cells (CTCs) are important prognostic indicators for malignancies. However, a reliable positive/negative cutoff value of non-epithelial (NE⁺: hybrid and mesenchymal) CTCs phenotype in prostate cancer (PCa) patients has not been established. Here, we aimed to determine the cutoff value and the prognostic value of NE⁺ CTCs in high-risk prostate cancer (HRPC) patients after radical prostatectomy (RP).

Background: The association between psychological stress and erectile dysfunction (ED) has been reported, but the causality of different types of stressors on ED is poorly understood. Aim: This study aims to investigate the causal relationship between various forms of psychological stress and ED through Mendelian randomization (MR). Methods: Several genome-wide association study (GWAS) datasets related to chronic psychological stress were used in this study for the identification of instrumental variables. Concurrently, a genome-wide association studies database provided the ED outcome data containing 6175 ED patients and 217 630 controls. The MR-Egger, inverse variance weighting (IVW), weighted median, and maximum likelihood methods were applied to conduct the MR study and IVW was taken as the primary criterion. Outcomes: Mendelian randomization analyses revealed that financial difficulties were associated with a heightened risk of ED, whereas the absence of stressors was linked to a decreased risk. Results: Among the various types of psychological stressors analyzed, financial difficulties were found to significantly increase the risk of ED (P = .022, OR = 4.343, 95%CI = 1.240-15.216). In contrast, other stressors did not significantly elevate the risk of ED. Furthermore, the absence of these stressors was associated with a reduced risk of ED (P = .009, OR = 0.211, 95% CI = 0.066-0.681). Clinical implications: This study emphasizes the enormous impact of psychological stress, especially financial hardship, in increasing the risk of ED. Strengths and limitations: This study is the first to employ MR analysis to investigate the causal relationship between various stressors and ED. However, this study did not consider the influence of non-genetic factors such as living environment and lifestyles. Conclusion: Psychological stress, particularly financial difficulties, can increase the risk of ED, while the absence of such stressors appears to be protective. Consequently, it is imperative to enhance medical education and awareness among economically disadvantaged populations and to address the detrimental effects of adverse lifestyles.

Wang W, et al. World J Mens Health. 2025 Aug;43:e62. https://doi.org/10.5534/wjmh.250060

Background: U2AF homology motif kinase 1 (UHMK1) has been associated with RNA processing and protein phosphorylation, thereby influencing tumor progression. The study aimed to explore its regulatory mechanisms and biological functions in human prostate cancer (PCa). Methods: In this study, we systematically evaluated the expression and prognostic significance of UHMK1 in public databases, followed by validation through immunohistochemistry (IHC) in PCa specimens. Both gain-of-function and loss-of-function experiments were conducted to elucidate the role of UHMK1 in vitro and in vivo. Additionally, a series of molecular and biochemical assays were performed to investigate the regulatory mechanisms underlying UHMK1 activity. Results: Our findings revealed that UHMK1 expression was significantly upregulated in PCa tissues and correlated with poor patient prognosis, as demonstrated by analysis of public datasets and confirmed by immunohistochemical staining. Functional studies showed that UHMK1 depletion suppressed tumor cell proliferation and metastasis, while its overexpression promoted these processes. Mechanistically, we identified that UHMK1 phosphorylates nuclear receptor coactivator 3 (NCOA3), which subsequently activates activating transcription factor 4 (ATF4) to upregulate methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) transcription. Interestingly, MTHFD2 was found to reciprocally enhance UHMK1 expression, establishing a positive feedback loop. Conclusions: In conclusion, our data suggest that the UHMK1-MTHFD2 axis forms a positive feedback loop that drives PCa progression. Targeting this loop represents a promising therapeutic strategy for restraining prostate cancer development and progression.

Background: Ureteral stents, including internal stents and stentless techniques, are commonly employed in urological procedures such as urinary stone management and deformity correction. However, their use in radical cystectomy for bladder cancer remains relatively limited. This study aimed to compare the efficacy of internal stent, external stent, and no-stent treatments for ureteroileal anastomosis in laparoscopic radical cystectomy (LRC) combined with ileal orthotopic neobladder (IONB). The goal was to compare postoperative outcomes and complications to identify the optimal stent choice. Methods: A retrospective analysis was conducted on 51 patients who underwent LRC with IONB between April 2013 and December 2023. Patients were divided into three groups: internal stent (Group A), external stent (Group B), and no stent (Group C). Baseline characteristics, perioperative data, and postoperative complications were compared across three groups. Results: Among the 51 patients (42 males, 9 females; median age: 62 years), internal stents were used in 18 (35.3%, Group A), external stents in 20 (39.2%, Group B), and no stents in 13 (25.5%, Group C) patients. Group A demonstrated significantly shorter hospital stays compared to Groups B and C (P=0.02). Abnormal renal function occurred less frequently in Group A (16.7%) and Group B (15.0%) than in Group C (53.8%, P=0.04). Early postoperative hydronephrosis was significantly different among the three groups (Group A: 5.6%, Group B: 5.0%, Group C: 38.5%; P=0.02). Ureteroileal anastomotic stricture (UIAS) was observed less frequently in Group A (0%) than in Group B (12.5%) and Group C (20.0%, P=0.01). No significant differences were found in other perioperative characteristics or complications. Conclusions: Internal stents reduce early postoperative complications, including hydronephrosis and renal dysfunction, while lowering the risk of late UIAS. Internal stent use is a safe and effective option that promotes faster recovery and better postoperative outcomes.

It is unknown when inosine was first employed as a renoprotective agent in the context of kidney transplantation procedures. However, there is no clinical evidence to support a protective role of inosine. The aim of this study was to investigate the effect of inosine on graft recovery. Data related to donors and recipients were retrieved from relevant records between 2015 and 2023. A total of 1138 kidney transplant cases were identified, including 1005 recipients who received a bolus of 1000 mg inosine and 133 recipients who did not receive inosine during transplantation surgery. The endpoints of the analysis included recipient recovery after transplantation as assessed by delayed graft function (DGF), peak estimated glomerular filtration rate (eGFR) after transplantation, and unfavorable graft function recovery. Given the high dimensionality of the donor and recipient variables, propensity score weighting analyses were conducted. No significant differences in the risk of DGF (OR = 0.80 [0.52, 1.22], p = 0.301), unfavorable graft function recovery (OR = 0.95 [0.61, 1.51], p = 0.842) or peak eGFR after transplantation (β = 1.61 [−4.33, 7.56], p = 0.594) were observed between the inosine and no-inosine groups via overlap weighting analysis. Intraoperative infusion of 1000 mg of inosine has no effect on graft recovery after kidney transplantation. Therefore, the practice of using inosine during kidney transplantation surgery is not supported by evidence.