The ceRNA PVT1 inhibits proliferation of ccRCC cells by sponging miR-328-3p to elevate FAM193B expression.

Clear cell renal cell carcinoma (ccRCC) is a common and fatal malignancy. Long noncoding RNAs (lncRNAs) have emerged as crucial biomarkers and regulators in many cancers, warranting the detailed investigation of their biological functions and molecular mechanisms. In this study, we explored the role and mechanism of plasmacytoma variant translocation 1 (PVT1), a competitive endogenous RNA (ceRNA) in ccRCC tissues in vitro and in vivo. We found that PVT1 is upregulated in ccRCC cells and promoted cell proliferation. Bioinformatic analysis, dual-luciferase reporter assays, argonaute 2-RNA immunoprecipitation (AGO2-RIP), quantitative PCR arrays, western blot assay, and rescue experiments were conducted to explore the underlying mechanisms of PVT1. Our analyses revealed that miR-328-3p was a direct target of PVT1 and that FAM193B was a direct target of miR-328-3p. FAM193B is upregulated in ccRCC tissues and promotes cell proliferation by activating the MAPK/ERK and PI3K/AKT pathways. Our results indicated that PVT1 promotes ccRCC cells proliferation by sponging miR-328-3p to upregulate FAM193B and activate the MAPK/ERK and PI3K/AKT pathways. Collectively, these results suggest that PVT1- miR-328-3p-FAM193B loop could serve as a potential biomarker and therapeutic target for ccRCC.

From "feeling" to "seeing": modification of the percutaneous peritoneal dialysis catheter insertion with an optical puncture system.

PURPOSE: Blind insertion limits the application of percutaneous peritoneal dialysis (PD) catheter placement. In this study, we first described the use of an optical puncture system in the PD catheter insertion, and investigated the feasibility and advantages of this modified technique. METHODS: This retrospective study included 65 patients with chronic kidney disease stage 5 (CKD5) who received ultrasound-guided percutaneous PD catheter insertion with or without optical puncture system assistance between June 2018 and July 2019. The patients' characteristics as well as the surgical outcomes and complications were compared between the modified group and the routine percutaneous insertion group. RESULTS: Twenty-five patients underwent optical puncture system assistant insertion, whereas 40 patients received routine percutaneous insertion. More patients had previous abdominal surgical histories in the modified group than those in the routine group (24.0% vs. 5.0%, p = 0.047). The time of accessing to the abdominal cavity was significantly shorter in the modified group (median [IQR]; 1.1 min [0.8-1.3] vs. 5.0 min [4.0-6.0]; p < 0.001). Meanwhile, the time of the whole procedure was also significantly shorter in the modified group (median [IQR]; 26.0 min [25.0-29.0] vs. 33.0 min [29.0-35.0]; p < 0.001). None of the patient in the modified group, while two patients (5.0%) in the routine group converted to open procedure. There were no significant differences in the short and long postoperative complications between the two groups. CONCLUSIONS: The operation of ultrasound-guided PD catheter placement with the optical puncture system is easy, safe, fast and accurate, whereby the PD catheter can be implanted percutaneously and visually under local anesthesia with minimal procedure-related complications. The visible puncture of the optical puncture system may facilitate ultrasound-guided percutaneous PD catheter insertion in patients with obesity and previous abdominal surgeries.

Advantages of retrograde flexible ureteroscopy in determining the etiology of painless hematuria originating from the upper urinary tract.

The present study investigated the use of retrograde flexible ureteroscopy (RFU) in the discrimination of the etiology of hematuria that originates from the upper urinary tract (UUT). The present study collected retrospective data for patients who presented with hematuria and cystoscopy-detected bleeding from the UUT between June 2006 and August 2018 in Ningbo First Hospital. All patients accepted RFU to determine the etiology of hematuria. Data regarding imaging examinations, surgery, pathology and complications were also collected and analyzed. In total, 65 patients (males, 38; females, 27) with a mean age of 63 years underwent RFU to determine the etiology of hematuria originating from the UUT. Using RFU, UUT tumors were found in 29 cases. Stones, polyps and atypical hyperplasia were found in two cases, and a definite diagnosis was not found in three cases. There were 17 cases without obvious abnormalities and nine cases were unable to undergo RFU due to ureteral stenosis. In patients who could not be diagnosed by imaging examination, 34.4% (11/32) were diagnosed with urothelial carcinoma by RFU, and these results were also confirmed by postoperative pathology. In the present study, no patient had severe complications after RFU. The present results suggested RFU may be used as a sensitive method to diagnose UUT tumors (78.4%; 29/37) and has strong specificity. RFU could be performed as a routine examination for patients with hematuria from the UUT.

The Effect of Ratio of Endoscope-Sheath Diameter on Intrapelvic Pressure During Flexible Ureteroscopic Lasertripsy.

PURPOSE: To clarify appropriate combinations of flexible ureteroscope (FURS) and ureteral access sheath (UAS), which can maintain a low intrapelvic pressure (IPP) during FURS with lasertripsy. METHODS: Four kinds of FURSs (Polyscope, Olympus URF-P6, Stroz Flex-Xc, and Olympus URF-V) and six sizes of UASs (11/13F × 36 cm, 11/13F × 46 cm, 12/14F × 36 cm, 12/14F × 46 cm, 13/15F × 36 cm, and 13/15F × 46 cm) were tested. A novel gas-liquid-pressure-control system (GLPCS) was used to maintain a stable and adjustable irrigation pressure form 50-500 cmH2O. IPPs and flow rates were recorded with different combinations of FURSs and UASs by using an in vitro fresh cadaveric porcine urinary system. RESULTS: The GLPCS can provide stable and adjustable water pressure. The ratio of outer diameter of FURSs and inner diameter of UASs (Ratio of Endoscope-Sheath Diameter-RESD) is essential to the IPP and flow rate. The highest IPP group is the combination of Olympus URS-V and 11/13F UAS with RESD of 0.87-0.88, the IPP is over 40 cmH2O when irrigation pressure comes to 250 cmH2O; Olympus URS-V in 12/14F UAS is at the middle group, RESD values of 0.81-0.82, IPP reaches 40 cmH2O at 500 cmH2O of irrigation pressure. Combinations with RESD ≤0.75 enjoy low IPPs (<13 cmH2O). Polyscope with 13/15F UASs has the highest flow rate (74.3-77.7 mL/min), whereas Olympus URS-V with 11/13F UASs has the lowest flow rate (17.0-17.3 mL/min). UAS length has less effect on the IPP and flow rate. CONCLUSIONS: To maintain a low IPP and acceptable flow rate during flexible ureteroscope lasertripsy, RESD should be kept below 0.75. UAS length has less effect on the IPP and flow rate.

Guide sheath-assisted ureteroscope lithotripsy for upper ureteral calculi: An observational study on 81 cases.

The present study assessed the clinical efficacy of guide sheath-assisted ureteroscope lithotripsy in the treatment of upper ureteral calculi. A total of 81 patients with upper ureteral calculi underwent ureteroscope lithotripsy assisted by a guide sheath between January 2012 and June 2014; of these, 63 patients were successfully treated with simple rigid ureteroscope lithotripsy assisted by a ureteral access sheath, and 18 patients were successfully treated with rigid and flexible ureteroscope lithotripsy assisted by a guide sheath. At 1 day after the surgery, ultrasound examination of kidneys, ureters and bladder, and urinary system computed tomography were used to re-check for residual stones, and 69 patients had stones with a diameter of <2 mm in the renal pelvis, while 12 had stones of 2-4 mm in diameter. The operation time was 30-115 min (average, 56.0±4.8 min); all patients underwent a successful surgical procedure. A total of 7 patients had an elevated temperature 37.4-39.1°C (mean temperature, 37.7±0.3°C) after the surgery, but no other major complications were noted. After 1 month, the residual stones were completely discharged, so that the stone clearance rate was 100%. All patients were followed up for 3-12 months and no associated complications occurred. Overall, ureteroscope lithotripsy assisted by a guide sheath for the treatment of upper ureteral calculi had the benefit of water injection and reflux functions, as well as enhanced vision, reduced pressure within the renal pelvis, good discharge of stones as well as an improved efficiency and success rate compared with simple ureteroscopic lithotripsy.

Uric acid stones, clinical manifestations and therapeutic considerations.

Uric acid stones account for 10%-15% of all urinary stones. Changes in dietary habits, environment or both can result in the increase of uric acid stones. The formation of uric acid stones is related to hyperuricosuria, low urinary volume and persistently low urinary pH. Diabetes and obesity also significantly increase the risk of stone formation. Dual-energy CT provides a convenient and reliable method for diagnosis. Stone composition analysis and 24-hour urine metabolic evaluations should be considered for further evaluation. Most small uric acid stones (diameter <2 cm) can be treated by pharmacotherapy or extracorporeal shock wave lithotripsy. However, ureteroscopy and other minimally invasive procedures should be reserved for larger stones (diameter ≥2 cm), or patients with concomitant urinary tract obstruction and/or infections. Additionally, adjustment of potential pathophysiologic defects by pharmacotherapy and dietary modification is strongly recommended for the prevention of uric stone recurrence.

Application of sequential factorial design and orthogonal array composite design (OACD) to study combination of 5 prostate cancer drugs.

Prostate cancer is one of the most common cancers among men in the United States. It is also a major leading cause of cancer death among men of all races. In order to treat prostate cancer, drug combinations are often applied. Drug combinations target at different pathways of cells can potentially lead to higher efficacy and lower toxicity due to drug synergy. In this paper, we sequentially applied a two-level design and a follow-up orthogonal array composite design (OACD) to investigate combinations of five anti-cancer drugs, namely, doxorubicin, docetaxel, paclitaxel, cis-dichlorodiamine platinum and dihydroartemisinin. Our initial screening using a two-level full factorial design identified doxorubicin and docetaxel as the most significant drugs. A follow-up experiment with an OACD revealed more complicated drug interactions among these 5 anti-cancer drugs. Quadratic effects of doxorubicin and paclitaxel appeared to be significant. A further investigation on contour plots of all the two-drug pairs indicated that combination of doxorubicin and docetaxel are the most effective companion, while the combination of cis-dichlorodiamine platinum and dihydroartemisinin showed unknown antagonistic effects which diminished the individual drug anti-cancer efficacy. These observations have significant practical implications in the understanding of anti-cancer drug mechanism that can facilitate clinical practice of better drug combinations.

Adenovirus-mediated LRIG1 expression enhances the chemosensitivity of bladder cancer cells to cisplatin.

Cisplatin (cis-diaminodichloroplatinum, CDDP) is one of the most effective chemotherapeutic agents that has been widely used in the treatment of many malignancies, including muscle invasive bladder cancer. However, development of CDDP resistance in cancer cells is a major obstacle to the effective treatment of bladder cancer. Therefore, the development of chemosensitizers to overcome the acquired resistance to chemotherapeutic agents is crucial. Previous studies have confirmed that the epidermal growth factor receptor (EGFR) and its signaling pathways are important in the chemoresistance of cancer cells against CDDP­induced cell apoptosis. In a preliminary study we showed that leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is the natural ligand of EGFR, and that the extracellular leucine-rich repeat (LRR) domain and immunoglobulin-like domains of LRIG1 were able to bind to the extracellular domain of EGFR, resulting in the downregulation of EGFR expression. Based on these findings, we hypothesized that LRIG1 may enhance the chemosensitivity of bladder cancer cells to CDDP. In the present study, LRIG1 was overexpressed by the adenovirus vector to determine the effect of LRIG1 on chemosensitivity in the T24 bladder cancer cell line and explored the possible mechanisms. The results showed that CDDP inhibited the growth of the T24 cell line and induced activation of EGFR. Overexpression of LRIG1 increased the inhibitory effect of CDDP on the T24 cell line, which may be associated with inactivation of the EGFR signaling pathway, followed by the decrease of Bcl-2 expression and a concomitantly induced expression of Bax. Based on these results, we concluded that the upregulation of LRIG1 expression inhibited the EGFR signaling pathway, activated the mitochondrial pathway of apoptosis and eventually increased the sensitivity of bladder cancer cells to CDDP.