Brusatol enhances MEF2A expression to inhibit RCC progression through the Wnt signalling pathway in renal cell carcinoma.

Renal cell carcinoma (RCC) is the most aggressive subtype of kidney tumour with a poor prognosis and an increasing incidence rate worldwide. Brusatol, an essential active ingredient derived from Brucea javanica, exhibits potent antitumour properties. Our study aims to explore a novel treatment strategy for RCC patients. We predicted 37 molecular targets of brusatol based on the structure of brusatol, and MEF2A (Myocyte Enhancer Factor 2A) was selected as our object through bioinformatic analyses. We employed various experimental techniques, including RT-PCR, western blot, CCK8, colony formation, immunofluorescence, wound healing, flow cytometry, Transwell assays and xenograft mouse models, to investigate the impact of MEF2A on RCC. MEF2A expression was found to be reduced in patients with RCC, indicating a close correlation with MEF2A deubiquitylation. Additionally, the protective effects of brusatol on MEF2A were observed. The overexpression of MEF2A inhibits RCC cell proliferation, invasion and migration. In xenograft mice, MEF2A overexpression in RCC cells led to reduced tumour size compared to the control group. The underlying mechanism involves the inhibition of RCC cell proliferation, invasion, migration and epithelial-mesenchymal transition (EMT) through the modulation of Wnt/ß-catenin signalling. Altogether, we found that MEF2A overexpression inhibits RCC progression by Wnt/ß-catenin signalling, providing novel insight into diagnosis, treatment and prognosis for RCC patients.

The status and characteristics of urinary stone composition in China.

OBJECTIVES: To explore characteristics of urinary stone composition in China, and determine the effects of gender, age, body mass index (BMI), stone location, and geographical region on stone composition. PATIENTS AND METHODS: We prospectively used Fourier-transform infrared spectroscopy to analyse stones from consecutive patients presenting with new-onset urolithiasis at 46 hospitals in seven geographical areas of China, between 1 June 2010 and 31 May 2015. Chi-squared tests and logistic regression analyses were used to determine associations between stone composition and gender, age, BMI, stone location, and geographical region. RESULTS: The most common stone constituents were: calcium oxalate (CaOx; 65.9%), carbapatite (15.6%), urate (12.4%), struvite (2.7%), and brushite (1.7%). CaOx and urate stones occurred more frequently in males, whereas carbapatite and struvite were more common in females (P < 0.01). CaOx and carbapatite were more common in those aged 30-50 and 20-40 years than in other groups. Brushite and struvite were most common amongst those aged <20 and >70 years. The detection rate of urate increased with age, whilst cystine decreased with age. Obese patients were more likely to have urate stones than carbapatite or brushite stones (P < 0.01). CaOx, carbapatite, brushite, and cystine stones were more frequently found in the kidney than other types, whereas urate and struvite were more frequent in the bladder (P < 0.01). Stone composition varied by geographical region. CONCLUSIONS: The most common stone composition was CaOx, followed by carbapatite, urate, struvite, and brushite. Stone composition differed significantly in patients grouped by gender, age, BMI, stone location, and geographical region.

Thioredoxin interacting protein (TXNIP) acts as a tumor suppressor in human prostate cancer.

Prostate cancer (PCa) is one of the most common malignant tumors in the world. Thioredoxin interacting protein (TXNIP) is downregulated in a variety of human tumors and plays an important role in tumor suppression. However, the expression level and biological functions of TXNIP in PCa have not been identified yet. Therefore, this study aims to investigate the expression and biological functions of TXNIP in PCa. We reported that the expression of TXNIP was significantly decreased in PCa and associated with clinicopathological features. Overexpression of TXNIP could significantly inhibited PC-3 cells proliferation, migration, invasion, and glucose uptake. Additionally, overexpression of TXNIP could remarkably block cell cycle in the G0/G1 phase and promoted cell apoptosis. Furthermore, TXNIP expression correlated inversely with GLUT1 expression in PCa. Taken together, our results for the first time revealed that TXNIP was decreased in PCa. Moreover, TXNIP might act as a tumor suppressor of PCa and correlated with tumor occurrence and development. Our findings cast a new light on better understanding the occurrence and development of PCa and indicated that TXNIP might be favorable for PCa molecular target therapy.

Suctioning Minimally Invasive Percutaneous Nephrolithotomy with a Patented System Is Effective to Treat Renal Staghorn Calculi: A Prospective Multicenter Study.

OBJECTIVES: To investigate the safety, efficacy, and practicability of minimally invasive percutaneous nephrolithotomy (MPCNL) with the aid of a patented irrigation clearance system in treating renal staghorn calculi. METHODS: From August 2009 to July 2014, 4 hospitals had executed a prospective multicenter study with a total of 912 cases. The patients were randomly divided into 3 groups: suctioning MPCNL, standard percutaneous nephrolithotomy (PCNL), and traditional MPCNL groups. Multiple operative and perioperative parameters were compared. RESULTS: Blood loss and intrapelvic pressure in the suctioning MPCNL group were significantly less than those in the standard PCNL group. The average operation time, intrapelvic pressure, and amount of bleeding in the suctioning MPCNL group were better than those in the traditional MPCNL group. The suctioning MPCNL used one tract more frequently and 2 or 3 tracts less frequently than the standard MPCNL and traditional MPCNL groups. The stone-free rate by one surgery in the suctioning MPCNL group was significantly higher than that in standard PCNL and traditional MPNCL groups. CONCLUSIONS: Suctioning MPCNL using our patented system shows several advantages in treating renal staghorn calculi, including minimal invasion, shorter operation time, lower intrapelvic pressure, less bleeding and the need for a smaller number of -percutaneous tracts, and higher stone clearance rate by one -surgery.

Development of Therapeutic dsP21-322 for Cancer Treatment.

Small activating RNAs (saRNAs) are a class of artificially designed short duplex RNAs targeted at the promoter of a particular gene to upregulate its expression via a mechanism known as RNA activation (RNAa) and hold great promise for treating a wide variety of diseases including those undruggable by conventional therapies. The therapeutic benefits of saRNAs have been demonstrated in a number of preclinical studies carried out in different disease models including cancer. With many tumor suppressor genes (TSGs) downregulated due to either epigenetic mechanisms or haploinsufficiency resulting from deletion/mutation, cancer is an ideal disease space for saRNA therapeutics which can restore the expression of TSGs via epigenetic reprogramming. The p21WAF1/CIP gene is a TSG frequently downregulated in cancer and an saRNA for p21WAF1/CIP known as dsP21-322 has been identified to be a sequence-specific p21WAF1/CIP activator in a number of cancer types. In this chapter, we review preclinical development of medicinal dsP21-322 for cancer, especially prostate cancer and bladder cancer, and highlight its potential for further clinical development.

Elevated expression of glutaminase confers glucose utilization via glutaminolysis in prostate cancer.

Cancer cells reprogram their metabolism towards aerobic glycolysis and elevated glutaminolysis, which contributes to the aggressive phenotype. Understanding how these metabolic pathways are regulated may provide critical targets for therapeutic intervention. Glutaminase (GLS1) is a key enzyme that converts glutamine to glutamate. In this study, we show the loss of GLS1 function by RNA interference or inhibitor diminished the rates of glucose utilization, growth and invasiveness of prostate cancer cells. We propose that GLS1 positively regulates glucose uptake in addition to glutaminolysis. Further, GLS1 involves the transcriptional repression of thioredoxin interacting protein (TXNIP), which is a potent negative regulator of glucose uptake and aerobic glycolysis. Most importantly, we provided direct evidence that elevated GLS1 expression was highly correlated with the tumor stage and progression in prostate cancer patients. Together, we defined a key role for GLS1 in coupling glutaminolysis of the TCA cycle with elevated glucose uptake and consequently the growth of prostate cancer cells. These data extends the role of GLS1 in regulating cell metabolism and the clinical utility of GLS1 inhibitors in the restriction of essential nutrients.

[Effects of adenovirus-mediated PTEN on the proliferation of prostate cancer PC-3 cells and expressions of cyclin D1 and p21].

OBJECTIVE: To construct a recombinant adenovirus expression vector containing the anti-oncogene PTEN and to investigate the effects of the PTEN gene on the proliferation of prostate cancer PC-3 cells and the expressions of cyclin D1 and p21 in the PC-3 cells. METHODS: The PTEN gene was amplified from the rat hippocampus by RT-PCR and cloned into the shuttle plasmid pEN-TR2A. The plasmids were constructed and amplified in 293A cells. Prostate cancer PC-3 cells were cultured in vitro and infected with the adenoviral vector carrying the PTEN gene (Ad-PTEN). The up-regulation of the PTEN protein was measured by indirect immuno-fluorescence assay; the expressions of PTEN, cyclin D1 and p21 in the cells infected with Ad-PTEN and Ad-LacZ were determined by RESULTS: The Western blot; and the effect of PTEN on the cell proliferation was detected by MTT assay and plate colony formation. recombinant adenoviral vector Ad-PTEN was successfully constructed. Western blot showed a significantly increased expression of the PTEN protein in the PC-3 cells infected with Ad-PTIEN (0.215 +/-0.065) as compared with that in the control ([0.052 +/-0.009], t = 4. 30, P <0.05) and the Ad-LacZ group ( [0. 056 +/- 0.008 ] , t =4.21, P <0.05). The expression of cyclin D1 was significantly lower in the Ad-PTEN-infected PC-3 cells (0. 256 +/- 0. 072) than in the control ( [0. 502 +/- 0. 087 ], t = 3.77, P < 0.05) and the Ad-LacZ group ([0.498 +/-0.081] , t =3.87, P <0.05), while the expression of p21 remarkably higher in the Ad-PTEN-infected PC-3 cells (0.589 +/-0. 076) than in the control ([0. 146 +/-0.026] , t = 9.55, P<0. 01) and the Ad-LacZ group ([0. 163 +/-0. 024] , t = 9.26, P <0.01). Ad-PTEN significantly inhibited the growth of the PC-3 cells (21.98%) at 48 h (t = 6.80, P <0.01). The colony formation rate of the PC-3 cells was (37.4 +/-4. 18)% in the Ad-PTEN group, significantly lower than (54.9 +/-4.81)% in the control (t =4.76, P<0.01) and (56.5 +/- 5.42)% in the Ad-LacZ group (t=4.83, P<0.01). CONCLUSION: The expression of PTEN induced by Ad-PTEN can significantly inhibit the proliferation of PC-3 cells, down-regulate the expression of cyclin D1, and up-regulate the expression of p21.

Increased abundance of bacteria of the family Muribaculaceae achieved by fecal microbiome transplantation correlates with the inhibition of kidney calcium oxalate stone deposition in experimental rats.

Background: The incidence of nephrolithiasis is increasing rapidly worldwide. Calcium oxalate is the most common constituent, contributing to approximately 80% of all kidney stones. The gut microbiome, through its oxalate-degrading ability, may play a role in decreasing morbidity due to urinary calculus. Fecal microbiome transplantation (FMT) has been reported to be effective in restoring the gastrointestinal microbial community in different conditions. The transplantation of whole communities that have oxalate-degrading function may be a more effective strategy than the transplantation of isolated strains. Methods: FMT was carried out in male guinea pigs and male Sprague-Dawley laboratory rats (SDRs). Fresh feces were collected from guinea pigs housed in metabolic cages. SDRs were divided into four groups: two groups received standard rat chow (SC) (groups SC and SC + FMT), and two groups were fed a 5% potassium oxalate diet (OD) (groups OD + phosphate-buffered saline (PBS) and OD + FMT). On day 14, groups OD + PBS, OD + FMT, and SC + FMT received either PBS or guinea pig feces by esophageal gavage. The composition of the microbiota of guinea pigs and SDRs was analyzed using a 16S rRNA gene sequencing approach. Biochemical analysis of urine samples from SDRs revealed the presence of calcium oxalate (CaOx) crystals, which were presumed to originate from kidney stones. Renal function was examined using real-time PCR analysis and immunohistochemical staining for renin, angiotensin-converting enzyme, and osteopontin (OPN) expression. Results: FMT resulted in a gut microbiota that was a mixture of guinea pig and SDR bacteria. A microbial network involving Muribaculaceae, Lactobacillus, and Bifidobacterium was activated by FMT in group OD + FMT. As a result, urinary oxalate, calcium, uric acid, creatinine and urea in urine samples were reduced significantly. Similarly, significant reduction of uric acid and blood urea nitrogen to creatinine ratio in serum samples was observed (p < 0.05). Microscopic observations revealed a high CaOx crystal score (4+) in the kidneys of rats in group OD + PBS, whereas a lower score (2+) was observed in the rats in group OD + FMT. Up-regulation of OPN and down-regulation of renin were also associated with FMT. Conclusion: A microbial network involving Muribaculaceae and other oxalate-degrading bacteria achieved by FMT was capable of reducing urinary oxalate excretion and CaOx crystal deposition in the kidney through increasing intestinal oxalate degradation. FMT may exert a renoprotective function in oxalate-related kidney stones.

PHF8-GLUL axis in lipid deposition and tumor growth of clear cell renal cell carcinoma.

For clear cell renal cell carcinoma (ccRCC), lipid deposition plays important roles in the development, metastasis, and drug resistance. However, the molecular mechanisms underlying lipid deposition in ccRCC remain largely unknown. By conducting an unbiased CRISPR-Cas9 screening, we identified the epigenetic regulator plant homeodomain finger protein 8 (PHF8) as an important regulator in ccRCC lipid deposition. Moreover, PHF8 is regulated by von Hippel-Lindau (VHL)/hypoxia-inducible factor (HIF) axis and essential for VHL deficiency-induced lipid deposition. PHF8 transcriptionally up-regulates glutamate-ammonia ligase (GLUL), which promotes the lipid deposition and ccRCC progression. Mechanistically, by forming a complex with c-MYC, PHF8 up-regulates TEA domain transcription factor 1 (TEAD1) in a histone demethylation-dependent manner. Subsequently, TEAD1 up-regulates GLUL transcriptionally. Pharmacological inhibition of GLUL by l-methionine sulfoximine not only repressed ccRCC lipid deposition and tumor growth but also enhanced the anticancer effects of everolimus. Thus, the PHF8-GLUL axis represents a potential therapeutic target for ccRCC treatment.

The Function Improved of the Newly Designed Magnetic-End Ureteric Stenting Retrieval Device: A Clinical Prospective Randomized and Control Trial in a Multicenter Study.

Objective: To demonstrate the advantage of our newly designed magnetic ureteric stenting retrieval device over traditional nonmagnetic ureteric stents and other retrieval devices without cystoscopy intervention on clinical application and cost-related outcomes. Patients and Methods. A total of 333 patients were recruited into two study groups: magnetic-end ureteral stent (Group A) and conventional ureteral stent (Group B). The effects were evaluated by Ureteral Stent Symptom Questionnaire (USSQ) scores, complications of the indwelling stent, visual analog scale (VAS) pain scores at stent removal, and cost-analysis outcomes between the magnetic ureteric stenting retrieval device and traditional double-J ureteral stent (DJUS) removed by cystoscopy. Results: The VAS of the pain score of patients undergoing magnetic stent removal with the retrieval device was 2 ± 0.97, whereas that of patients undergoing conventional ureteral stent removal with cystoscopy was 5.76 ± 1.53 (p < 0.001). The removal of magnetic stents by a retrieval device proved to be less painful than cystoscopy-mediated stent removal (p < 0.001). Obviously, the total cost for the magnetic stent removal was much lower than the conventional ureteral stent removal, although the magnetic stent costs more than the conventional ureteral stent. The improved magnetic stent used in our study showed a remarkable cost saving of 705/111 USD Chinese Yuan (CNY) per patient when compared with the conventional ureteral stent. Conclusion: We reported the integrated design features of the improved magnetic stent in the world, which was granted a patent in China. USSQ scores and rate of complications in the magnetic stent were as equally acceptable as a conventional stent. Furthermore, successful stent insertion rate reached 100% by both the antegrade and retrograde approaches, and no failure case of magnetic stent removal was reported in our study.

[Effects of staurosporine on the proliferation and apoptosis of prostate cancer PC-3 cells].

OBJECTIVE: To investigate the effects of staurosporine (ST) on the proliferation and apoptosis of prostate cancer PC-3 cells. METHODS: Prostate cancer PC-3 cells were treated in vitro with ST at 10(-8) mol/L. The expressions of cyclin A and cyclin D1 proteins in the cells were detected by Western blot, the effect of ST on the proliferation of the cells determined by MTT assay and plate colony formation, the apoptosis of the cells examined by flow cytometry, and their morphological changes observed under the light microscope. RESULTS: ST treatment markedly decreased the expressions of cyclin A and cyclin D1 in the PC-3 cells, and significantly inhibited the growth of the PC-3 cells (19.35%) at 48 h. (F = 31.06, P < 0.01). The colony formation rate of the PC-3 cells was (37.10 +/- 3.43) % in the ST group, significantly lower than (64.80 +/- 4.34) % in the control (chi2 = 14.59, P < 0.05) and (62.80 +/- 4.36) % in the DMSO group (chi2 = 12.50, P < 0.05), while the apoptosis rate of the cells was remarkably higher in the ST group ([19.6 +/- 2.20] %) than in the control ([5.33 +/- 1.40] %) and the DMSO group ([5.50 +/- 0.96] %) (F = 104.36, P < 0.01). Under the light microscope, the ST-treated cells were round with indistinct margins as compared with those of the other two groups. CONCLUSION: ST could significantly inhibit the proliferation and induce the apoptosis of PC-3 cells.

Holographic reconstruction technology used for intraoperative real-time navigation in robot-assisted partial nephrectomy in patients with renal tumors: a single center study.

BACKGROUND: To explore the efficacy and advantages of real-time navigation using holographic reconstruction (HR) technology combined with da VinciTM robotic system for partial nephrectomy (PN) in patients with renal tumor. METHODS: The clinical data of 41 patients with totally intrarenal tumors receiving robot-assisted partial nephrectomy (RAPN) from April 2018 to October 2020 in our department were collected and retrospectively analyzed. All operations were performed by the same surgeon. HR technology and three-dimensional (3D) reconstruction techniques were applied for real-time navigation to resect tumors using the da VinciTM robotic system. The relevant clinical parameters and surgical outcomes of the patients were recorded and analyzed. RESULTS: HR technology allowed accurate evaluation of tumors, renal hilus vessels, and surrounding organs during the operation. With real-time navigation HR, all cases were performed by RAPN. The mean operative time was 115.3±20.3 (range, 70-153) minutes, and the warm ischemia time (WIT) was 18.7±3.9 (range, 13-28) minutes. The estimated blood loss (EBL) was 98.8±18.7 (range, 60-141) mL. Negative surgical margins were reported in all cases. Patients with absence of grade ≤1 Clavien-Dindo complications. Compared with the clinical outcomes of standard RAPN, as reported in the literature, HR-assisted technology reduced the mean operative time, the WIT, and the EBL in patients undergoing RAPN. Therefore, combining HR with robotic abdominal surgery can enhance the efficiency of locating blood vessels and allow for more accurate resection of tumors. CONCLUSIONS: As a novel and promising computer digital technology, HR can significantly improve the success of RAPN operations. This retrospective study demonstrated that HR-assisted operations resulted in shorter operation times and less perioperative complications and were thus safer and more effective in patients with renal tumors compared with RAPN not used HR.

[Effects of intraprostatic injection of botulinum toxin A (BTX-A) on benign prostate hyperplasia].

OBJECTIVE: To investigate the effects of intraprostatic injection of botulinum toxin A (BTX-A) on benign prostate hyperplasia (BPH) in rats. METHODS: Models of BPH were established in adult male Sprague-Dawley rats by injection of testosterone propionate, and then divided into three BTX-A groups, injected with BTX-A into the ventral prostate at the doses of 5 U, 10 U and 20 U, a negative control group, injected with saline only, and a sham operation group, with 12 in each. The prostates of the animals were harvested at 2 or 4 weeks after the injection, their volumes and weights measured, histological changes examined by HE staining, and glandular and interstitial areas semi-quantified by the image analysis system. RESULTS: Two rats died in the 20 U group within 3 days after BTX-A injection. Compared with the saline group, the 5 U, 10 U and 20 U BTX-A groups showed significant decreases in prostatic volume (P < 0.01, 0.01 and 0.05), weight, and glandular and interstitial areas as well as atrophic epithelia in the glandular tube at 2 weeks. These changes were lessened at 4 weeks, especially in the 5 U group. CONCLUSION: Intraprostatic injection of BTX-A induces obvious atrophy and histological changes of the prostate, but meanwhile may potentially result in death at a large dose.

Survival after radical cystectomy for bladder cancer: Multicenter comparison between minimally invasive and open approaches.

OBJECTIVE: To investigate oncological outcomes in patients with bladder cancer who underwent minimally invasive radical cystectomy (MIRC) or open radical cystectomy (ORC). METHODS: We identified patients with bladder cancer who underwent radical cystectomy (RC) in 13 centers of the Chinese Bladder Cancer Consortium (CBCC). Perioperative outcomes were compared between MIRC and ORC. The influence of surgical approaches on overall survival (OS) and cancer-specific survival (CSS) in the entire study group and subgroups classified according to pathologic stage or lymph node (LN) status was assessed with the log-rank test. Multivariable Cox proportional hazard models were used to evaluate the association among OS, CSS and risk factors of interest. RESULTS: Of 2 098 patients who underwent RC, 1 243 patients underwent MIRC (1 087 laparoscopic RC and 156 robotic-assisted RC, respectively), while 855 patients underwent ORC. No significant differences were noted in positive surgical margin rate and 90-day postoperative mortality rate. MIRC was associated with less estimated blood loss, more LN yield, higher rate of neobladder diversion, longer operative time, and longer length of hospital stay. There was no significant difference in OS and CSS according to surgical approaches (p=0.653, and 0.816, respectively). Subgroup analysis revealed that OS and CSS were not significantly different regardless of the status of extravesical involvement or LN involvement. Multivariable Cox regression analyses showed that the surgical approach was not a significant predictor of OS and CSS. CONCLUSIONS: Our study showed that MIRC was comparable to conventional ORC in terms of OS and CSS.

[The mRNA expression of P16(ink4a) and HST2 in benign prostatic hyperplasia tissues: a pilot study].

OBJECTIVE: To investigate the expressions of the aging gene P16(ink4a) and anti-aging gene HST2 in benign prostatic hyperplasia (BPH). METHODS: Twenty-three BPH and eighteen normal prostate specimens were collected and total RNA was extracted, followed by the reverse transcriptase polymerase chain reaction (RT-PCR). The expressions of P16(ink4a) was detected by semi-quantitative analysis in BPH and normal prostate tissues. RESULTS: P16(ink4a) mRNA, rather than HST2, was expressed in the BPH and normal prostate tissues. Semi-quantitative analysis showed that the P16(ink4a) mRNA expression in the normal prostate tissues (0.4868 +/- 0.545 was significantly higher than in the BPH tissues (0.2783 +/- 0.0268, with a statistical difference in between (P < 0. 05). CONCLUSION: P16(ink4a) might play an important role in the pathogenesis of BPH and is probably one of the factors of cell aging escape.

Modified Mechanical Percussion for Upper Urinary Tract Stone Fragments After Extracorporeal Shock Wave Lithotripsy: A Prospective Multicenter Randomized Controlled Trial.

OBJECTIVE: To investigate the effectiveness of modified mechanical percussion for eliminating upper urinary tract stone fragments after extracorporeal shock wave lithotripsy. MATERIALS AND METHODS: We assigned patients aged 18-60 years with upper urinary tract calculi to the modified mechanical percussion (trial) or observation (control) group. Kidney-ureter-bladder radiography and ultrasound were used for diagnostic evaluation. The primary outcome was the stone-expulsion rate (SER) at 6 hours. The first stone-expulsion time, the SER at 3, 12, and 24 hours, the stone-free rate, additional interventions, and adverse events (AEs) were recorded. RESULTS: A total of 120 patients underwent randomization: 60 for each group. The mean first stone-expulsion time in the trial and control groups was 6.75 and 13.58 hours, respectively (P = .001). The SERs at 3, 6, and 12 hours in the trial group were 51.8%, 75.4%, and 76.8%, respectively, which were higher than the control group (all P <.05). Among patients who expelled fragments within 6 hours, the stone-free rates were improved at 1 week (P = .002) and at 2 weeks (P = .000). Patients needed fewer additional interventions in the trial group (P = .035). AEs occurred in 42.9% (24 of 56) and 67.9% (38 of 56) of the patients in the trial and control groups, respectively (P = .008). Age, gender, stone size and location, and SER at 24 hours did not differ significantly among the groups. CONCLUSION: Modified mechanical percussion significantly improved SERs and accelerated stone passage after shock wave lithotripsy, resulting in a stone-free status with a lower risk of AEs and reduced need for additional interventions.

Efficacy and Safety of Tamsulosin in Medical Expulsive Therapy for Distal Ureteral Stones with Renal Colic: A Multicenter, Randomized, Double-blind, Placebo-controlled Trial.

BACKGROUND: Recent large high-quality trials have questioned the clinical effectiveness of medical expulsive therapy using tamsulosin for ureteral stones. OBJECTIVE: To evaluate the efficacy and safety of tamsulosin for distal ureteral stones compared with placebo. DESIGN, SETTING, AND PARTICIPANTS: We conducted a double-blind, placebo-controlled study of 3296 patients with distal ureteral stones, across 30 centers, to evaluate the efficacy and safety of tamsulosin. INTERVENTION: Participants were randomly assigned (1:1) into tamsulosin (0.4mg) or placebo groups for 4 wk. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary end point of analysis was the overall stone expulsion rate, defined as stone expulsion, confirmed by negative findings on computed tomography, over a 28-d surveillance period. Secondary end points included time to stone expulsion, use of analgesics, and incidence of adverse events. RESULTS AND LIMITATIONS: Among 3450 patients randomized between September 1, 2011, and August 31, 2013, 3296 (96%) were included in the primary analysis. Tamsulosin benefits from a higher stone expulsion rate than the placebo (86% vs 79%; p<0.001) for distal ureteral stones. Subgroup analysis identified a specific benefit of tamsulosin for the treatment of large distal ureteral stones (>5mm). Considering the secondary end points, tamsulosin-treated patients reported a shorter time to expulsion (p<0.001), required lower use of analgesics compared with placebo (p<0.001), and significantly relieved renal colic (p<0.001). No differences in the incidence of adverse events were identified between the two groups. CONCLUSIONS: Our data suggest that tamsulosin use benefits distal ureteral stones in facilitating stone passage and relieving renal colic. Subgroup analyses find that tamsulosin provides a superior expulsion rate for stones >5mm, but no effect for stones ≤5mm. PATIENT SUMMARY: In this report, we looked at the efficacy and safety of tamsulosin for the treatment of distal ureteral stones. We find that tamsulosin significantly facilitates the passage of distal ureteral stones and relieves renal colic.

Intuitionistic Linguistic Multiple Attribute Decision-Making with Induced Aggregation Operator and Its Application to Low Carbon Supplier Selection.

The main focus of this paper is to investigate the multiple attribute decision making (MADM) method under intuitionistic linguistic (IL) environment, based on induced aggregation operators and analyze possibilities for its application in low carbon supplier selection. More specifically, a new aggregation operator, called intuitionistic linguistic weighted induced ordered weighted averaging (ILWIOWA), is introduced to facilitate the IL information. Some of its desired properties are explored. A further generalization of the ILWIOWA, called intuitionistic linguistic generalized weighted induced ordered weighted averaging (ILGWIOWA), operator is developed. Furthermore, by employing the proposed operators, a MADM approach based on intuitionistic linguistic information is presented. Finally, an illustrative example concerning low carbon supplier selection and comparative analyses are conducted to demonstrate the effectiveness and practicality of the proposed approach.

PBOV1 promotes prostate cancer proliferation by promoting G1/S transition.

Prostate cancer (PC) is one of the leading causes of cancer death in men, and thus, finding new regulators is critical for PC therapy. Prostate and breast cancer overexpressed 1 (PBOV1) is overexpressed in breast, prostate, and bladder cancers, as it is upregulated in the serum of patients with PC, but the role of PBOV1 in PC has not been studied. In this article, we found that PBOV1 was indeed overexpressed in PC cells; PBOV1 overexpression promoted cell proliferation and colony formation ability and arrested cell cycle in the G0/G1 phase and tumorigenicity ability in vitro, whereas knockdown of PBOV1 reduced these effects. Further analysis of PBOV1 overexpression inhibited cell cycle inhibitors, P21 and P27, and increased the phosphorylation level of Rb and cyclin D1 expression, suggesting that PBOV1 promoted cell proliferation through promoting G1/S transition.