Clinical study of UMP and RIRS in 1.0-2.0 cm diameter renal/upper ureteral calculi.

BACKGROUND: The purpose of this study was to compare the efficacy and safety of Ultra-mini-percutaneous nephrolithotomy (UMP) and Retrograde intrarenal surgery (RIRS) for renal/upper ureteral calculi in 1.0-2.0 cm diameter. METHODS: From October 2017 to October 2022, the surgical treatment of patients with renal/upper ureteral calculi in 1.0-2.0 cm diameter who were admitted to our hospital was retrospectively analyzed. They were divided into two groups, the UMP group (sixty-two cases) and the RIRS group (one hundred and nine cases), according to the different surgical methods. Baseline data includes general information, stone size, location, CT value, hydronephrosis, creatinine level, etc. RESULTS: Intraoperative blood loss was 33.6 ± 8.5 ml in the UMP group was significantly more than 4.3 ± 0.7 ml in the RIRS group (P < 0.05). Intraoperative renal pelvis pressure of UMP group 10.5 ± 1.3 mmHg was significantly lower than RIRS group 23.6 ± 5.6 mmHg (P < 0.05). The incidence of postoperative infection was higher in the RIRS group (thirteen cases [11.93%]), and one case ([1.61%]) in the UMP group (P < 0.05). Routine CT scans on the second day and two months after surgery showed that the stone clearance rates in the UMP group were 87.1% and 93.5%, respectively, higher than those in the RIRS group (69.7% and 79.8%, respectively; P < 0.05). CONCLUSION: UMP has the advantage of a higher stone-free rate but a higher risk of injury and bleeding. The advantages of RIRS include less trauma, less bleeding, and faster recovery, but lower stone-free rates and a higher risk of infection.

[Effects of simvastatin on the proliferation and apoptosis of prostatic epithelial RWPE-1 cells].

OBJECTIVE: To investigate the effects of simvastatin on the proliferation and apoptosis of prostatic epithelial RWPE-1 cells. METHODS: RWPE-1 cells cultured in vitro were treated with simvastatin at 0, 10, 20, and 40 µmol/L for 24, 48, and 72 hours followed by determination of their proliferation by MTT assay, and their apoptosis by flow cytometry. The mRNA and protein expressions of Bcl-2, Bax, and Cx43 were detected by fluorescence quantitative RT-PCR and Western blot, respectively. RESULTS: After 72 hours of treatment with simvastatin at 10, 20, and 40 µmol/L, the inhibition rates of the RWPE-1 cells were (21.07 ± 6.41)%, (34.87 ± 9.65)%, and (47.18 ± 10.88)%, respectively, significantly higher than (1.21 ± 0.54)% in the control group (P < 0.05) and in a dose-dependent manner (P < 0.05); the cell apoptosis rates were (0.066 ± 0.016)%, (0.126 ± 0.023)%, and (0.192 ± 0.025)%, respectively, remarkably higher than (0.015 ± 0.005)% in the control (P < 0.05) and also in a dose-dependent manner (P < 0.05); the mRNA and protein expressions of Bcl-2 were decreasing while those of Bax and Cx43 increasing with the increased concentration of simvastatin (P < 0.05). The expression of Cx43 was correlated negatively with that of Bcl-2 but positively with that of Bax. CONCLUSION: Simvastatin inhibits the proliferation of prostate epithelial cells and induce their apoptosis by acting on the gap junctional intercellular communication.

[Oral medication of statins retards the progression of benign prostatic hyperplasia and lower urinary tract symptoms].

OBJECTIVE: To determine whether oral statins can delay the progression of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). METHODS: We conducted a retrospective cohort study of 50-69-year-old males who came for physical examination in our hospital between January 2003 and December 2008. We designed the inclusion criteria, followed them up for 5 years, and investigated the relationship of oral statins with the clinical progression of BPH and LUTS. RESULTS: Totally, 653 men met the inclusion criteria and were included in this study, of whom 283 were treated with oral statins (group 1) while the other 370 with none (group 2). There were no statistically significant differences between the two groups in age and baseline IPSS, Qmax, and prostate volume (PV) (P > 0.05). During the follow-up, 24 cases in group 1 and 35 cases in group 2 were excluded for obvious dys-uria. A gradual increase was observed in IPSS in both groups 1 and 2 year by year from the baseline to the 5th year of follow-up, but significantly lower in the former group (4.27 +/- 1.16, 4.63 +/- 1.05, 5.27 +/- 0.96, 6.41 +/- 1.04, 7.21 +/- 1.21, and 7.93 +/-1.50) than in the latter (4.24 +/- 1.35, 5.26 +/- 1.23, 6.84 +/- 1.20, 8.75 +/- 1.84, 10.82 +/- 3.01, and 12.98 +/- 4.21) (P < 0.01); a gradual decrease was seen in Qmax, though markedly higher in group 1 ([26.56 +/- 2.09], [24.06 +/- 1.94], [21.33 +/- 1.66], [19.24 +/- 1.54], [17.44 +/- 1.53], and [16.27 +/- 1.37] ml/s) than in group 2 ([26.74 +/- 2.40], [23.62 +/- 2.01], [20.63 +/- 1.69], [17.72 +/- 1.48], [14.82 +/- 1.11], and [11.86 +/- 1.24] ml/s) (P < 0.01); and a gradual increase was found in PV, but remarkably smaller in the former group ([19.82 +/- 4.94], [22.60 +/- 4.99], [25.80 +/- 5.20], [27.92 +/- 5.05], [29.11 +/- 5.24], and [29.97 +/- 5.26] ml) than in the latter ([20.21 +/- 4.78], [24.30 +/- 4.98], [28.50 +/- 5.14], [32.84 +/- 4.77], [36.99 +/- 4.78], and [40.90 +/- 4.78] ml) (P < 0.01). Longer medication of statins was associated with better efficacy. CONCLUSION: Oral statins can significantly delay the clinical progression of BPH and LUTS.

MicroRNA-4735-3p Facilitates Ferroptosis in Clear Cell Renal Cell Carcinoma by Targeting SLC40A1.

Objective: Clear cell renal cell carcinoma (ccRCC) is the major histopathological subtype of renal cancer, and ferroptosis is implicated in the pathogenesis of ccRCC. The present study was aimed at investigating the role and underlying mechanisms of microRNA-4735-3p (miR-4735-3p) in ccRCC. Methods: Human ccRCC cell lines were transfected with the miR-4735-3p mimic or inhibitor to manipulate the expression of miR-4735-3p. Cell proliferation, colony formation, cell migration, cell invasion, cell death, oxidative stress, lipid peroxidation, and iron metabolism were determined. To validate the necessity of solute carrier family 40 member 1 (SLC40A1), human ccRCC cell lines were overexpressed with SLC40A1 using adenoviral vectors. Results: miR-4735-3p expression was reduced in human ccRCC tissues and cell lines but elevated upon ferroptotic stimulation. The miR-4735-3p mimic increased, while the miR-4735-3p inhibitor decreased oxidative stress, lipid peroxidation, iron overload, and ferroptosis of human ccRCC cell lines. Mechanistic studies identified SLC40A1 as a direct target of miR-4735-3p, and SLC40A1 overexpression significantly attenuated iron overload and ferroptosis in the miR-4735-3p mimic-treated human ccRCC cell lines. Conclusion: miR-4735-3p facilitates ferroptosis and tumor suppression in ccRCC by targeting SLC40A1.

Low expression of miR-99b promotes progression of clear cell renal cell carcinoma by up-regulating IGF1R/Akt/mTOR signaling.

OBJECTIVE: Dysfunctions of microRNAs have been implicated in the progression of clear cell renal cell carcinoma (ccRCC). Here, we investigated the roles of miR-99b and miR-99b* in ccRCC development. METHODS: The expression levels of miR-99b and miR-99b* in tumor and tumor-adjacent tissues from ccRCC patients were quantified by quantitative Real-Time PCR (qRT-PCR). MicroRNA mimics and inhibitors were employed to evaluate the functions of miR-99b and miR-99b*. The effects of miR-99b on the proliferation and migration of ccRCC cells were analyzed by MTT and wound-healing assays, respectively. The effect of miR-99b on the expression of its target gene IGF1R and mTOR was determined by western blotting and qRT-PCR. RESULTS: The abundances of miR-99b and miR-99b* were lower in ccRCC tissues than in the tumor-adjacent tissues from patients. Similarly, the expression of these two microRNAs was higher in the normal kidney HK-2 cells than in the ccRCC cell lines. Moreover, miR-99b and miR-99b* inhibited the proliferation and migration of ccRCC cells. MiR-99b was found to down-regulate IGF1R and mTOR expression, likely through targeting their mRNAs to induce degradation. Consistently, the mRNA levels of IGF1R and mTOR were higher in ccRCC tissues than in the tumor-adjacent tissues, and Akt, a downstream factor of IGF1R, was highly activated correspondingly in ccRCC tissues. CONCLUSION: The low expression of miR-99b and miR-99b* contributes to ccRCC development and miR-99b acts as an onco-suppressor by suppressing IGF1R and mTOR expression to down-regulate IGF1R/AKT/mTOR signaling.

Inhibition of miR-423-5p suppressed prostate cancer through targeting GRIM-19.

OBJECTIVE: To determine the effect of miR-423-5p on the progression of prostate cancer (PC). METHODS: miR-423-5p and GRIM-19 expressions were detected by qRT-PCR and western blot. PC cell proliferation was measured by MTT assay. PC cell apoptosis was detected by flow cytometry. Dual luciferase reporter assay was used to confirm the interaction between miR-423-5p and GRIM-19. RESULTS: Compared with normal prostate tissues and prostate epithelial cell HPrEC, miR-423-5p was up-regulated in human PC tissues and PC3 cells, whereas GRIM-19 expression was decreased. Inhibition of miR-423-5p suppressed PC3 cell proliferation, promoted PC3 cell apoptosis, and decreased anti-apoptosis protein BCL-2 expression. GRIM-19 was a target of miR-423-5p, and GRIM-19 was negatively regulated by miR-423-5p in PC3 cells. In addition, miR-423-5p knockdown inhibited the proliferation and promoted the apoptosis of PC3 cells through GRIM-19. In vivo experiments showed that miR-423-5p inhibitor administration reduced tumor volume, down-regulated miR-423-5p and GRIM-19 expressions in PC tissues of nude mice. CONCLUSION: Inhibition of miR-423-5p suppressed PC through targeting GRIM-19.

Notch 1 is a valuable therapeutic target against cell survival and proliferation in clear cell renal cell carcinoma.

Notch 1 is a key component of the Notch pathway, which performs a crucial role in clear cell renal cell carcinoma (CCRCC) development. The present study aimed to investigate whether Notch 1 could serve as a potential target for CCRCC treatment. Firstly, an association analysis was performed using 52 CCRCC cases and 30 normal controls. The results indicated that Notch 1 protein expression in renal tissues was closely associated with the incidence of CCRCC. In addition, higher Notch 1 expression in CCRCC tissues was positively associated with higher tumor-node-metastasis stage and Fuhrman grade, in addition to larger tumor size. Subsequently, an in vitro study was conducted to examine the biological functions of Notch 1 in CCRCC 786-O cells through inhibiting the Notch 1 expression with Notch 1-specific small interfering RNA (siRNA). As a result, the inhibition of Notch 1 expression by increasing concentrations of Notch 1-specific siRNA dose-dependently decreased cell proliferation and increased cell apoptosis in 786-O cells. Furthermore, B-cell lymphoma-2 and procaspase-3 expression exhibited a dose-dependent decrease accompanied with a dose-dependent inactivation of the Akt/mammalian target of rapamycin (mTOR) signaling pathway in Notch 1 siRNA-treated 786-O cells. These findings demonstrated that Notch 1 was associated with CCRCC carcinogenesis and progression, the underlying mechanism of which was that Notch 1 acted as an activator for cell proliferation and a suppressor for cell apoptosis through the Akt/mTOR signaling-dependent pathway in CCRCC. In conclusion, the present study confirmed that Notch 1 is a valuable target against cell survival and proliferation in CCRCC treatment.