Cisplatin-based chemotherapy often results in the development of chemo-resistance when used to treat bladder cancer (BC), which is difficult to overcome. Recent data indicate that pyruvate kinase M2 (PKM2), a glycolytic enzyme for Warburg effect, is strongly upregulated in BC, and contributes to the cisplatin resistance in BC. However, the underlying mechanisms remain unclear. In this study, we also found that the expression level of PKM2 is also higher in cisplatin resistant BC cells and tumors. Down-regulation of PKM2 by siRNA or inhibition of PKM2 by shikonin re-sensitized the cisplatin resistant T24 cells. Shikonin and cisplatin together exhibit significantly greater killing effects than when used alone. Interestingly, we found shikonin kills the T24 cisplatin resistant cells by inducing necroptosis, as the cell death could not inhibited by apoptosis inhibitor, z-VAD, but compromised by RIP3 inhibitor, GSK872, or RIP3 siRNA. In contrast, shikonin induced apoptosis in T24 parental cells. We further investigate the underlying mechanism, and found that the dysregulation of Bcl-2 family proteins, including Bcl-2, PUMA, Bax, play an important role in deciding that shikonin kills the BC cells by necroptosis or apoptosis. Collectively, our results suggested that inducing necroptosis is an alternative way to overcome the apoptosis resistant in BC therapy, and orchestrating the regulation of Bcl-2, PUMA, and Bax in BC cisplatin resistant cells may improve the therapy effect of cisplatin in BC tumor.

Non-muscle invasive bladder cancer (NMIBC) patients often have fewer treatment options, and suffer the progression of disease due to mechanisms that are not clear, as well as due to its diversity. This study was designed to explore the molecular mechanism of bladder cancer through an RNA-seq. In addition to conventional analyses, we also simplified the network through modularization using the WGCNA algorithm, with the help of the topological overlapping matrix and hierarchical cluster tree, which are based on the PPI network of STRING. Furthermore, the hub genes were confirmed through survival analyses in the independent cohorts ( n = 431). Among them, 15 genes were significantly associated with poor prognosis. Finally, we validated the results at mRNA and protein level using qRT-PCR, IHC and western blotting. Taken together, our research is important for the prediction, as well as the prospective clinical development of drug targets and biomarkers.

MicroRNAs (miRNAs) have emerged as critical regulators in cancer progression. miR‑613 has been reported as a tumor suppressor gene in many types of human cancers. However, the function of miR‑613 in renal cell carcinoma (RCC) remains unclear. In the present study, the authors aimed to detect the expression of miR‑613 and its function in RCC cell lines. miR‑613 was reported to be significantly downregulated RCC cell lines. Functional analyses demonstrated that overexpression of miR‑613 significantly decreased RCC cell proliferation and invasion. Bioinformatics analysis showed that Frizzled7 (FZD7) was a predicted target of miR‑613, which was verified by dual‑luciferase reporter assay, reverse transcription quantitative‑polymerase chain reaction and western blot analysis. Restoration of FZD7 significantly reversed the suppressive effects of miR‑613 on RCC cell proliferation and invasion. Taken together, the results of the present study indicated that miR‑613 functions as a tumor suppressor that inhibits RCC cell proliferation and invasion by targeting and inhibiting FZD7, providing novel insight into RCC pathogenesis and a potential therapeutic target for RCC.

The aim of this study was to investigate the role of TAp63 and DeltaNp63 isoforms in uterine cervical cancers. The messenger RNA (mRNA) and protein expressions of TA and DeltaN forms as well as alpha, beta, and gamma isoforms of p63 were studied in seven SiHa, ME-180, SNU17, SNU902, SNU1160, SNU703, and SNU1299 human papillomavirus (HPV)-positive uterine cervical squamous cell carcinoma (SCC) cell lines, one HT3 HPV-negative SCC cell line, and one HeLa adenocarcinoma cell line using reverse transcription-polymerase chain reaction (RT-PCR) and western blotting. Fresh nonneoplastic and neoplastic tissues of uterine cervical and endometrial cancers were also studied. RT-PCR for TA and DeltaN form and three isoforms of p63 showed positive bands for both TA and DeltaN forms and for all three isoforms in cervical cancer cell lines but weak band for alpha isoform in HPV-negative HT3 SCC cell line and no band for beta isoform in HeLa adenocarcinoma cell line. RT-PCR for TA and DeltaN and three isoforms of p63 mRNA in tissue samples showed positive bands in almost all samples, except for gamma isoform, the expression was weak or absent in nonneoplastic tissues compared with neoplastic tissues. In western blotting, cancer cell lines and both nonneoplastic and neoplastic tissue samples showed expression of TA and DeltaN, and gamma isoform but beta isoform expression with or without alpha isoform was only found in cancer cell lines and neoplastic tissues. beta isoform, possibly of DeltaNp63, may be considered as an important isoform in uterine cervical squamous cell carcinogenesis.

The study explored the clinical efficacy of a type 5 phosphodiesterase inhibitor (PDE5i) combined with Ziyin Baihuo granules in the treatment of patients suffering from erectile dysfunction (ED) with yin deficiency and fire-hyperactivity syndrome. A total of 163 patients with erectile dysfunction were divided into observation and control groups. The observation group took tadalafil (Cialis) and Ziyin Baihuo granules orally, and the control group took only tadalafil orally, for 12 weeks. An additional 40 healthy people were selected as a normal group for comparison of the sex hormone levels before and after treatment of the participants in the erectile dysfunction group. After treatment, the symptoms of dry throat and tongue, tidal fever and night sweats, liking cold and avoiding heat, and waist pain showed significant improvement in the observation group ( p < .05). Compared with before treatment, the clinical indexes of erectile function in the control group and the observation group were improved after treatment ( p < .05). After treatment, Ziyin Baihuo granules combined with tadalafil restored the abnormal indexes of blood ( p < .05) in the observation group. Our research shows that PDE5i combined with Ziyin Baihuo granules could effectively improve erectile function.

This study aimed to compare the success rates of two approaches for seminal vesiculoscopy: through the interior of the prostatic utricle and through the neck of the prostatic utricle. The patients were divided into two groups based on the seminal vesiculoscopy used. Group A was an interior of the prostatic utricle group (152 cases), and group B was a neck of the prostatic utricle group (146 cases). The general clinical data, intraoperative conditions and surgical results of the two groups were compared. Compared with group A, group B had a higher surgical success rate (94.5% vs. 62.5%, p < .001), a shorter operation time (33 min vs. 45 min, p < .001), less blood loss (0.5 ml vs. 2 ml, p < .001), a higher pain relief rate (86.6% vs. 52.3%, p < .001), a higher remission rate of haemospermia (82.2% vs. 58.5%, p = .011), a lower recurrence rate of pain (10.4% vs. 35.4%, p < .001), a lower recurrence rate of haemospermia (15.6% vs. 37.7%, p = .014), a higher symptom remission rate of the lower urinary tract (90.9% vs. 50.0%, p = .030), a higher remission rate of scrotal moisture (84.6% vs. 45.5%, p = .042) and a higher remission rate of frequent spermatorrhea (80.0% vs. 55.6%, p = .033). Seminal vesiculoscopy undertaken through the neck of the prostatic utricle has the characteristics of high success rate, short operation time and good surgical effect and is worthy of promotion and application.

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ObjectiveTo evaluate the safety and efficacy of transvesical incision in the treatment of ejaculatory duct obstruction.MethodsThe clinical data of 26 male infertile patients with ejaculatory duct obstruction were retrospectively analysed at the First Affiliated Hospital of Zhengzhou University from June 2020 to August 2021. All patients were treated with seminal vesicle neck incision for ejaculatory duct obstruction. The general clinical characteristics, intraoperative conditions and postoperative effects on the patients were recorded, and the therapeutic effect was evaluated.ResultsThe ejaculatory duct was found through fenestration, and the seminal vesicle gland was smoothly entered in 25 patients (96.2%). Among them, 22 cases underwent bilateral endoscopy and three underwent unilateral endoscopy. Sperm appeared in 23 cases (88.5%) 3 months after surgery. The sperm concentration and motility postoperatively at 6 months were higher than that at 3 months postoperatively. No postoperative complications, such as epididymitis or retrograde ejaculation, occurred.ConclusionSearching for the ejaculatory duct via the neck of the prostatic utricle, assisted by a low-energy holmium laser, is a new method for the treatment of ejaculatory duct obstruction. Microscopic vision is clear using this approach and the postoperative complications are few, which has high value for clinical application.