Bioinformatics analysis reveals that CBX2 promotes enzalutamide resistance in prostate cancer.

Enzalutamide (Enz) is commonly utilized as the initial treatment strategy for advanced prostate cancer (PCa). However, a notable subset of patients may experience resistance to Enz, resulting in reduced effectiveness. Utilizing Gene Expression Omnibus (GEO) databases, we identified CBX2 as a crucial factor in mediating resistance to Enz, primarily due to its inhibitory effect on the P53 signaling pathway. Silencing of CBX2 using small interfering RNA (siRNA) led to elevated levels of P53 expression in LNCaP cells. This indicates that CBX2 may have a critical effect on PCa Enz resistance and could serve as a promising therapeutic target for individuals with Enz resistance.

Chronic oral administration of L-carnitine induces testicular injury: in vivo evidence.

PURPOSE: While L-carnitine is commonly used to treat oligoasthenozoospermia, concerns have been raised regarding its potential harm to spermatogenesis. This study aims to investigate the potential testicular toxicity of long-term oral administration of L-carnitine. METHODS: In this study, we refer to the clinical adult dosage and mode of L-carnitine administration, and after converting to mouse doses, mice were daily intragastrical administered L-carnitine to investigate whether it was harmful to the testis. The investigation involved assessing its potential testicular toxicity through histopathological staining, sperm motility analysis, and quantitative real-time PCR. RESULTS: Our results showed that L-carnitine increased sperm motility after 14 days of continuous administration, but increased luminal exfoliated spermatogenic cells occurred in the testis, and TUNEL results showed increased apoptotic cells. Compared with the control group, the mRNA expression of the spermatogenic cell marker at each stage was decreased in mice treated for 14 consecutive days of L-carnitine. After 50 days of continuous administration followed by 14 days of drug withdrawal, the total sperm motility of mice was almost 0, and a large number of abnormal eosinophilic spermatogenic cells appeared in the testis. These indicate that oral L-carnitine for more than 14 days impairs spermatogenesis in mice, and sudden discontinuation of administration results in substantial death of established spermatogenic cell populations. CONCLUSION: Our findings suggest that chronic oral administration of L-carnitine impairs spermatogenic function in the testis. The oral administration of L-carnitine to enhance sperm motility should not exceed the 2/5 point of the spermatogenic cycle.

Prospective learning curve analysis of en bloc resection of bladder tumor using an ex vivo porcine model.

BACKGROUND: As a relatively new surgical technique, the learning curve of en bloc resection of bladder tumor (ERBT) in ex vivo models remains unaddressed. This study aimed to explore the learning curve of ERBT in an ex vivo porcine model. METHODS: In this prospective study, eight endoscopists without prior experience in ERBT were divided into two groups: junior endoscopists, with less than 100 transurethral resection of bladder tumor (TURBT) procedure experience, and senior endoscopists, with at least 100 TURBT procedure experience. Each endoscopist performed 30 ERBT procedures on artificial lesions in an ex vivo porcine bladder model. The procedure time, perforation, en bloc resection status, and absence of detrusor muscle (DM) were recorded. The inflection points were identified using cumulative sum (CUSUM) analysis. Procedure results were compared between the two phases and two groups. RESULTS: In all, 240 artificial lesions were successfully resected using ERBT. The CUSUM regression line indicated the inflection point at the 16th procedure for the junior endoscopists and at the 13th procedure for the senior endoscopists. In both groups, the procedure time, perforation, piecemeal resection, and DM absence rates were significantly lower in the consolidation phase than in the initial phase. The procedure time for the senior endoscopists was lower than for the junior endoscopists in both phases. CONCLUSIONS: ERBT performance improved significantly after reaching the inflection point of the learning curve in the ex vivo model. We recommend a minimum of 16 ERBT procedures in ex vivo models for urologists with less than 100 TURBT experience and a minimum of 13 procedures for those with at least 100 TURBT experience before advancing to live animal training or supervised clinical practice.

Rotatable Bi-Channel En Bloc Resection of Bladder Tumor for Non-Muscle-Invasive Bladder Cancer in an Ex Vivo Porcine Model.

En bloc resection of bladder tumor (ERBT) is a promising alternative for non-muscle-invasive bladder cancer management. However, the tumor characteristics and surgeon's experience influence its application. Therefore, in this pilot study, we developed a technique called "rotatable bi-channel en bloc resection of bladder tumor (RBC-ERBT)" and assessed its feasibility, efficacy, and safety compared with those of conventional ERBT. In an ex vivo porcine bladder model, 160 bladder lesions of varying morphologies (exophytic and flat) and sizes (1 and 2 cm) were created and evenly distributed across different locations. A total of 160 procedures were performed, with the ERBT and RBC-ERBT group each exhibiting 80 lesions. RBC-ERBT had a significantly higher technical success rate than ERBT (98.8% vs. 77.5%) for exophytic and flat lesions of both sizes and dome lesions. The procedure time was significantly shorter in the RBC-ERBT group, particularly for flat lesions, lesions with a 2 cm diameter, and lesions located at the dome. RBC-ERBT had a significantly lower piecemeal resection rate than ERBT (0% vs. 18.8%). The incidence of perforation or detrusor muscle sampling did not differ between the groups. Compared with conventional ERBT, RBC-ERBT offered improved success rates, reduced resection times, and effective management of challenging lesions.

Improving effects of telmisartan on spermatogenic disorder induced by fractionated low-dose irradiation in mice.

BACKGROUND: Male infertility is a hot problem worldwide, but there are few treatments, especially male infertility caused by irradiation is difficult to treat. The aim of this study was to investigate and evaluate novel drugs for the treatment of male infertility caused by irradiation. METHODS: we randomly divided 18 male BALB/c mice into 3 groups: control, irradiated, and telmisartan. Both irradiated and telmisartan group completed whole-body 0.5 Gy five times irradiation, and the telmisartan group received intraperitoneal injection of telmisartan (1.2 mg/kg) daily on the next day after irradiation, and all groups were sampled on day 25 after irradiation. RESULTS: Sperm motility results show that total sperm motility of irradiated group was significantly lower compared with control group, and testicular HE results showed that testis in irradiated group were severely damaged. Compared with irradiated group, the total sperm motility, sperm concentration, testicular index, Johnsen score, and the seminiferous tubule layer numbers were higher in telmisartan group (P < 0.05). The immunohistochemical staining showed γ-H2AX expression is higher in telmisartan group compared with irradiated group. And the relative mRNA expression of PLZF, GFRA1, STRA8, DMRT1, SPO11, SYCP2, OVOL2, CCNA1, TJP3, RUNX2, TXNDC2 TNP1, and PRM3 in telmisartan group was all significantly higher than irradiated group (P < 0.05). CONCLUSION: In conclusion, in vivo experiments confirmed that telmisartan ameliorated the spermatogenic disorder in mice caused by fractionated low-dose irradiation via promoting spermatogenesis.

The Comparison Study of Anatomic Vapor-incision Technique (AVIT) Using the 180W-XPS Greenlight Laser and Photoselective Vaporization of the Prostate for the Treatment of Benign Prostatic Hyperplasia.

OBJECTIVE: To prospective compared the preoperative parameters and postoperative functional outcomes between anatomic vapor-incision technique (AVIT) and the photoselective vaporization of prostate (PVP) with Greenlight 180W-XPS. METHODS: Total 174 BPH patients were enrolled in the study and 86 cases, 88 cases were underwent with traditional PVP and AVIT, respectively. The relevant pre-, intra-, and postoperative data were recorded and compared between the both groups. RESULTS: No significant differences were observed between both groups in baseline characteristics and no major complications (capsule perforation and TUR syndrome) occurred intraoperatively. In AVIT group, the energy consumption and energy density were greater than those in PVP group. The operative time and laser time were longer in AVIT group than it in PVP group. Compared to the AVIT group, the incidence of irritative symptoms after operation was higher in the PVP group. During the follow-up period, the functional outcomes (IPSS, QoL, prostate volume and PSA level) in both groups were significant improved compared to the baseline. The reduction of prostate volume and PSA level were significant greater in AVIT group than it in PVP group. CONCLUSION: Compared to PVP, AVIT is safe and efficacious treatment for BPH patients with more adenoma removal and more improvements of clinical outcomes. But the long-term follow-up data is needed to evaluate the functional outcomes and retreatment rates.