Bezotome and bezotriptor are useful endoscopic devices to disintegrate huge, hard bezoars and achieve complete clearance.

TGF- is a key profibrotic factor, but targeting TGF- to prevent fibrosis also abolishes its protective anti-inflammatory effects. Here, we investigated the hypothesis that we can redirect TGF- signaling by preventing downstream profibrotic interaction of -catenin with T cell factor (TCF), thereby enhancing the interaction of-catenin with Foxo, a transcription factor that controls differentiation of TGF- induced regulatory T cells (iTregs), and thus, enhance anti-inflammatory effects of TGF- In iTregs derived from EL4 T cells treated with recombinant human TGF-1 (rhTGF-1) , inhibition of-catenin/TCF transcription with ICG-001 increased Foxp3 expression, interaction of -catenin and Foxo1, binding of Foxo1 to the Foxp3 promoter, and Foxo transcriptional activity. Moreover, the level of-catenin expression positively correlated with the level of Foxo1 binding to the Foxp3 promoter and Foxo transcriptional activity. T cell fate mapping in Foxp3 Ly5.1/5.2 mice revealed that coadministration of rhTGF-1 and ICG-001 further enhanced the expansion of iTregs and natural Tregs observed with rhTGF-1 treatment alone. Coadministration of rhTGF-1 with ICG-001 also increased the number of Tregs and reduced inflammation and fibrosis in the kidney fibrosis models of unilateral ureteric obstruction and ischemia-reperfusion injury. Notably, ICG-001 prevented the fibrosis in distant organs (lung and liver) caused by rhTGF-1. Together, our results show that diversion of -catenin from TCF- to Foxo-mediated transcription inhibits the-catenin/TCF-mediated profibrotic effects of TGF- while enhancing the -catenin/Foxo-mediated anti-inflammatory effects. Targeting-catenin/Foxo may be a novel therapeutic strategy in the treatment of fibrotic diseases that lead to organ failure.

Background and objectivesThe effects of uric acid-lowering therapy in patients with chronic kidney disease (CKD) remain uncertain. Therefore, we undertook a systematic review and meta-analysis to investigate the effects of uric acid-lowering agents on major clinical outcomes of CKD.Design, setting, participants, and measurementsAccording to the pre-specified protocol that was registered with PROSPERO (No. CRD42016038030), we searched systematically in MEDLINE, EMBASE, and the Cochrane Library for trials up to February 2016. Prospective, randomized, controlled trials assessing the effects of uric acid-lowering agents on cardiovascular and kidney outcomes in patients with CKD were included. Random-effects analytical methods were used.ResultsSixteen eligible trials were identified, providing data for 1,211 patients with CKD, including 146 kidney failure events and 69 cardiovascular events. Uric acid-lowering therapy produced a 55% relative risk (RR) reduction (95% confidence interval [95% CI], 31–64) for kidney failure events (P < 0.001), and a 60% RR reduction (95% CI, 17–62) for cardiovascular events (P < 0.001), but had no significant effect on the risk of all-cause death (RR, 0.86; 95% CI, 0.50–1.46). The mean differences in rate of decline in the estimated glomerular filtration rate (4.10 mL/min/1.73 m2 per year slower in uric acid-lowering therapy recipients, 95% CI, 1.86–6.35) and the standardized mean differences in the change in proteinuria or albuminuria (−0.23 units of standard deviation greater in uric acid-lowering therapy recipients; 95% CI, −0.43 to −0.04) were also statistically significant.ConclusionsUric acid-lowering therapy seemed to improve kidney outcomes and reduce the risk of cardiovascular events in adults with CKD.

BackgroundDietary protein restriction has long been thought to play an important role in the progression of chronic kidney disease (CKD); however, the effect of dietary protein on the rate of decline in kidney function remains controversial.ObjectiveWe undertook a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the influence of protein restriction on chronic kidney disease.MethodOvid MEDLINE (from 1946 to March 5, 2016), EMBASE (from 1966 to March 5, 2016), and the Cochrane Library (Inception to March 5, 2016) were searched to identify RCTs comparing different levels of protein intake for at least 24 weeks in adult patients with CKD. The outcomes included kidney failure events, the rate of change in estimated glomerular filtration rate (eGFR) per year, all cause death events, and changes in proteinuria, serum phosphorus concentration, serum albumin, and body mass index (BMI).ResultsNineteen trials with 2492 subjects were analyzed. A low protein diet reduced the risk of kidney failure (odds ratio (OR) = 0.59, 95% CI: 0.41 to 0.85) and end-stage renal disease (ESRD) (OR = 0.64, 95% CI: 0.43 to 0.96), but did not produce a clear beneficial effect for all cause death events (OR = 1.17, 95% CI: 0.67 to 2.06). The change in the mean difference (MD) for the rate of decline in the eGFR was significant (MD: −1.85, P = 0.001), and for proteinuria (MD: −0.44, P = 0.02). A low protein diet also reduced the serum phosphorus concentration (MD: −0.37, 95% CI: −0.5 to −0.24) and BMI (MD: −0.61, 95% CI: −1.05 to −0.17). However the change in albumin presented no significant difference between two groups (MD: 0.23, 95% CI: −0.51 to 0.97).ConclusionsBased on the findings of our meta-analysis, protein-restricted diet may reduce the rate of decline in renal function and the risk of kidney failure for CKD populations, but did not produce a clear beneficial effect for all cause death events. Besides However, the optimal level of protein intake in different participants is left unanswered, and the nutritional status should be regarded with caution.