Jiayu Liu

Resistance to enzalutamide (Enza) in castration-resistant prostate cancer (CRPC) is linked to poor prognosis. While KDM5B is highly expressed in Enza-resis

Persistent androgen receptor (AR) signaling, metabolic alterations, and changes in the immune microenvironment are contributing factors to the progression of prostate cancer (PCa); however, therapeutic strategies capable of simultaneously targeting these interconnected vulnerabilities remain limited. Here, we identify a combinatorial regimen consisting of dihydroartemisinin and eupatilin (D&E) as a suppressor of PCa progression through coordinated disruption of tumor-intrinsic survival signaling and protumor immune interactions. Functionally, D&E suppressed the proliferation of PCa cells. Mechanistically, D&E induces ferroptosis in PCa cells, as evidenced by lipid peroxidation, intracellular iron accumulation, malondialdehyde elevation, and glutathione reduction. We further identified AR as an important target of D&E and found that it promotes resistance to ferroptosis by sustaining the SLC7A11 antioxidant axis through transcriptional activation of SLC7A11. Upstream, D&E inhibited the NF-κB subunit p65, which transcriptionally maintains AR expression, thus establishing an NF-κB/AR/SLC7A11 signaling cascade underlying ferroptosis resistance in PCa. Beyond tumor-intrinsic effects, D&E also remodels the tumor microenvironment. Specifically, AR-high tumor cells were found to facilitate M2-like macrophage polarization. In turn, M2-like macrophages could secrete SPP1, which potentially augments malignant properties and AR signaling in tumor cells via the CD44 pathway, thereby constituting a protumorigenic positive feedback loop. Notably, D&E attenuated the M2-like phenotype, reduced SPP1 secretion, and reduced macrophage-mediated promotion of PCa proliferation. In immunocompetent mouse models, D&E further synergized with anti-PD-L1 to suppress PCa progression. Together, these findings indicate that D&E exert antitumor effects in PCa by promoting ferroptosis-associated cell death and modulating macrophage-associated microenvironmental signaling, with potential therapeutic relevance particularly in AR-positive PCa.

The maintenance and regulation of cancer stem cell (CSC) stemness are crucial for tumor progression; however, the mechanisms underlying tumor stemness regulation remain poorly understood. Herein, we discovered that the enhanced hypoxia-induced transforming growth factor beta induced protein (TGFBI) in bladder cancer (BLCA) promotes the establishment of a stemness loop in the tumor microenvironment, facilitating the maintenance of CSC stemness and malignant proliferation. Clinically, the upregulation of hypoxic TGFBI in BLCA correlates with malignant BLCA features and poor prognosis. Mechanically, TGFBI can stabilize the structural integrity of disulfide bonds in Cys48 and Cys77 of growth differentiation factor 15 (GDF15), leading to aberrant function activity of GDF15 and secretion. Interestingly, secreted GDF15 consequently not only further upregulates CSC-related gene expression but also induces the activation of cancer-associated fibroblasts through the transforming growth factor beta receptor type 2 (TGFBR2)–transforming growth factor β (TGFβ)–TGFBI self-regulatory feedback loop to promote stemness in BLCA. TGFBI knockdown or GDF15 inhibition results in a decrease in functional proteins associated with stemness maintenance, which suppresses bladder CSCs’ self-renewal and effectively improves the efficacy of chemotherapy. Together, these findings demonstrate the pivotal role of TGFBI in BLCA’s stemness maintenance and BLCA progression, highlighting that the inhibition of the TGFBI/GDF15 axis is a potential therapeutic strategy for the amelioration of cancer chemotherapy.

Background: Postoperative anxiety following voluntary medical male circumcision (VMMC) poses a significant health challenge, with limited telemedicine access and inadequate communication compromising recovery and adherence. Narrative-based interventions have shown promise in reducing psychological distress in other contexts, and large language models may enable automated follow-up, but their role in VMMC care remains underexplored. Objective: We evaluated the effect of a narrative-enhanced tool (NET) on anxiety, sleep quality, quality of life, and pain management and identified risk factors for postoperative anxiety. We also assessed the feasibility of an artificial intelligence–assisted consultation (AAC) system in improving follow-up efficiency. Methods: From October 1, 2023, to April 29, 2024, patients aged ≥15 years undergoing VMMC were recruited and randomized 1:1 to a standardized risk tool (SRT) or NET group. In addition to the routine postoperative communication, the NET group received a narrative video highlighting positive recovery experiences. Both groups accessed an AAC chatbot for automated follow-ups. Primary outcomes were anxiety levels measured by the 7-item Generalized Anxiety Disorder scale (GAD-7), sleep quality measured by Pittsburgh Sleep Quality Index, quality of life measured by 3-level EuroQoL 5D questionnaire, and pain levels measured by Numerical Rating Scale. Secondary outcomes included analgesic use, satisfaction, and health care worker efficiency. Repeated measures ANOVA assessed trends and regression identified risk factors for anxiety. Results: Between October 1, 2023, and April 29, 2024, 671 eligible participants were enrolled, with 388 completing the 30-day follow-up (SRT group: n=189, mean age 26.21, SD 3.69 years; NET group: n=199, mean age 26.41, SD 3.56 years; P =.60). Both groups exhibited increased anxiety levels, diminished quality of life, and poorer sleep quality during the 30-day postoperative period. However, compared to SRT, the NET group demonstrated lower GAD-7 scores (7.06, SD 2.73 vs. 9.95, SD 3.50; P <.001), improved sleep quality (12.29, SD 3.57 vs 13.20, SD 3.54; P =.01), higher quality of life scores (0.87, SD 0.07 vs 0.84, SD 0.09; P <.001), more regular analgesic use (154/173, 89.02% vs 100/169, 59.17%; P <.001), reduced opioid consumption (5/173, 2.89% vs 25/169, 14.79%; P <.001), and higher pain medication satisfaction (4.21, SD 0.69 vs 3.76, SD 0.97; P <.001). Multivariate analysis identified SRT assignment, inability to recall opioid risk levels, hematoma, swelling, and pain as independent risk factors for elevated GAD-7 scores. Implementation of the AAC substantially reduced health care worker follow-up time (2.34, SD 1.95 min vs 7.85, SD 2.65 min; P <.001). Conclusions: The study demonstrates that narrative is effective in reducing anxiety, improving quality of life, and improving pain management post-VMMC. The integration of artificial intelligence into clinical follow-up protocols has the potential to enhance health care worker efficiency without compromising patient satisfaction.

Background: The relationship between dietary oxidative balance score (DOBS) and diabetes-related renal events remains unclear.Methods: In this study, the associations between serum micronutrients and diabetic nephropathy (DN) in participants matched by propensity score (PSM) were retrospectively analyzed. And next, a cross-sectional analysis was performed with the National Health and Nutritional Examination Survey (NHANES) database. Weighted multivariate adjusted logistic regression models, dose–response curves, subgroup analysis, and mediation analysis were the main methods of this study. Finally, sensitivity analyses were performed by PSM and multiple imputation (MI).Results: Retrospective findings suggest that single antioxidants may not be representative of an individual’s overall antioxidant levels. The results of the cross-sectional study indicated that the higher the DOBS, the greater the beneficial effects on DN [Q4 vs. Q1: OR (95% CI): 0.78 (0.63, 0.96), p for trend = 0.008] and renal function in DN [Q4 vs. Q1: β (95% CI): 5.395 (1.590, 9.199), p for trend = 0.004]. The above correlations were linear negative correlation (p for nonlinear = 0.989) and linear positive correlation (p for nonlinear = 0.593) respectively. Chronic inflammation mediated the above associations to some extent. The results of sensitivity analysis were consistent with the original analysis.Conclusion: Higher dietary antioxidant exposure has a positive effect on DN and renal function in DN, mediated partially by chronic inflammation.

Flexible ureteroscopy (f-URS) is a minimally invasive surgical technique used for treating urinary tract stones. While general anesthesia (GA) is the standard method used, it comes with risks. Local anesthesia (LA) is a safer and more cost-effective alternative to GA, and its use in f-URS could potentially reduce patients' risks and increase accessibility to treatment. This study aims to investigate the feasibility, safety, and efficacy of using LA for f-URS in treating stones, as an initial experience in the diagnosis related group (DRG) era of China. Patients who met the inclusion and exclusion criteria and were continuously included in the study Between 2021 and 2023. We analyzed the stone free status, postoperative complication rate, hospitalization costs, and presented key points of the procedure performed under LA that we had summarized over the past two years. A study of 614 patients undergoing f-URS under LA for urinary stones in our hospital showed 83.4% stone-free rate with a mean operative time of 44.12 ± 16.63 minutes; 18 patients experienced fever postoperatively, and 12 had ureteral injuries. No severe complication was reported. The cost of LA was found to be only 1.7% of the DRG payment, which is around $40. The highest VAS scores were observed during the sheath insertion, with STAI scores decreasing during and after surgery. The study revealed that f-URS administered under LA was a well-tolerated, efficient, safe, and economical procedure. In the DRG era, this new anesthetic option for f-URS provides urologists with a more cost-effective alternative.

Background: Prostate cancer (PCa) is the second most common cause of cancer-related deaths in American men. Even though increasing evidence has disclosed the competitive endogenous RNA (ceRNA) regulatory networks among cancers, the complexity and behavior characteristics of the ceRNA network in PCa remain unclear. Our study aimed to investigate the forkhead box A1 (FOXA1)-related ceRNA regulatory network and ascertain potential prognostic markers associated with PCa.Methods: RNA sequence profiles downloaded from The Cancer Genome Atlas (TCGA) were analyzed to recognize differentially expressed genes (DEGs) derived from tumor and non-tumor adjacent samples as well as FOXA1^low and FOXA1^high tumor samples. The enrichment analysis was conducted for the dysregulated mRNAs. The network for the differentially expressed long non-coding RNA (lncRNA)-associated ceRNAs was then established. Survival analysis and univariate Cox regression analysis were executed to determine independent prognostic RNAs associated with PCa. The correlation between DUSP2 and immune cell infiltration level was analyzed. Tissue and blood samples were collected to verify our network. Molecular experiments were performed to explore whether DUSP2 is involved in the development of PCa.Results: A ceRNA network related to FOXA1 was constructed and comprised 18 lncRNAs, 5 miRNAs, and 44 mRNAs. The MAGI2-AS3~has-mir-106a/has-mir-204~DUSP2 ceRNA regulatory network relevant to the prognosis of PCa was obtained by analysis. We markedly distinguished the MAGI2-AS3/DUSP2 axis in the ceRNA. It will most likely become a clinical prognostic model and impact the changes in the tumor immune microenvironment of PCa. The abnormal MAGI2-AS3 expression level from the patients’ blood manifested that it would be a novel potential diagnostic biomarker for PCa. Moreover, down-expressed DUSP2 suppressed the proliferation and migration of PCa cells.Conclusions: Our findings provide pivotal clues to understanding the role of the FOXA1-concerned ceRNA network in PCa. Simultaneously, this MAGI2-AS3/DUSP2 axis might be a new significant prognostic factor associated with the diagnosis and prognosis of PCa.

Background: Several groups proved kidney‐sparing surgery (KSS) had equivalent oncological outcomes compared with radical nephroureterectomy (RNU) for the low‐risk upper urinary tract urothelial carcinoma (UTUC) patients. Whereas, the clinical efficacy of KSS for high‐risk UTUC, especially for distal high‐risk ureteral carcinoma, remains unclear.Objective: To evaluate the feasibility of KSS for patients with distal high‐risk ureter cancer.Materials and methods: Our study included 22 patients who diagnose the distal high‐risk ureter cancer and underwent KSS between May 2012 and July 2021 in the First Affiliated Hospital of Chongqing Medical University. Overall survival (OS), confirmed as the primary endpoint of present study, was assessed by a blinded independent review committee (BIRC). The secondary endpoints included the postoperative SF‐36 (the short form 36 health survey questionnaire) score, progression‐free survival (PFS), postoperative complications, and so on.Results: Overall, 17 (77.3%) and 5 (22.7%) patients underwent segmental ureterectomy (SU) and endoscopic ablation (EA), respectively. By the cut‐off date, the mean OS was 76.3 months (95% Cl: 51.3–101.1 months) and the mean PFS was 47.0 months (95% Cl: 31.1–62.8 months), respectively. And the SF‐36 score in a majority of patients was >300 (90.9%).Conclusion: This is a daring endeavor to explore the clinical efficacy of KSS in distal high‐risk ureter cancer based on the high‐risk UTUC criteria, which shows satisfactory results in the long‐term prognosis and operation‐associated outcomes. However, future randomized or prospective multicenter studies are necessary to validate our conclusions.

To compare the feasibility and effectiveness of gum chewing to promote gastrointestinal (GI) recovery and prevent postoperative ileus (POI) in patients who underwent robot-assisted partial nephrectomy (RALPN), all subjects who met the enrollment criteria were randomly divided into the CG group (n = 23) and the control group (n = 29). No intervention other than chewing gum had been set between the two groups. We took the time of first bowel sound, exhaust, defecation, liquid diet, and solid diet as the study endpoints, and performed statistical analysis between the two groups. Baseline and postoperative data of patients were also recorded and analyzed. The time of first flatus, the first defecation, hospital stay, first liquid diet, and first solid diet in the chewing gum group were significantly shorter than those in the control group (all P < 0.05). CG can be an effective approach to promote bowel function recovery and prevent POI after robot-assisted partial nephrectomy.

Solitary fibrous tumor (SFT) is a relatively rare type of mesenchymal neoplasm that occurs most frequently in the pleura. However, SFT originating from the prostate is particularly uncommon and onl...