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Short bowel syndrome patients have a marked intestinal dysbiosis with type II SBS characterized by Proteobacteria and type III SBS featured by Lactobacillus, resulting in altered functional profiles of fecal microbiomes.

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BACKGROUND & AIMS: Little is known about the effects of endoscopic balloon dilation (EBD) for strictures of the upper gastrointestinal (UGI) tract in patients with Crohn's disease (CD). We performed a pooled analysis of the efficacy and safety of EBD for UGI CD-associated strictures. METHODS: We searched Embase, Medline, and the Cochrane library, as well as bibliographies of relevant articles, for cohort studies of adults with CD and strictures of the stomach or duodenum (up to the ligament of Treitz) who underwent EBD through December 2016. We obtained data from 7 international referral centers on 94 patients who underwent 141 EBDs. We performed a patient-level meta-analysis of data from published and unpublished cohort studies to determine mechanical and clinical success. We performed a time-to-event analysis to assess symptom recurrence and need for redilation or surgery. The patients analyzed had strictures of the duodenum (n [ 107), stomach (n [ 30), or spanning both (n [ 4). RESULTS: The rate of technical success for EBD was 100%, with 87% short-term clinical efficacy; major complications arose from 2.9% of all procedures. During a median follow-up period of 23.1 months, 70.5% of patients had a recurrence of symptoms, 59.6% required redilation, and 30.8% required surgical intervention. Patients whose disease was located in the small bowel had a higher risk for symptom recurrence (hazard ratio [HR], 2.1; P [ .003). Asian race (HR, 2.8; P < .001) and location of disease in the small bowel (HR, 1.9; P [ .004) increased the need for redilation. Prestenotic dilation was a risk factor for needing surgery earlier (HR, 1.9; P [ .001).

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Histone deacetylase 6 (HDAC6) contributed to the pathogenesis of rhabdomyolysis-induced acute kidney injury (AKI) and selective inhibition of HDAC6 activity may be a promising strategy for the treatment of AKI. Compound 23BB as a highly selective HDAC6 inhibitor was designed, synthesized by our lab and exhibited therapeutic potential in various cancer models with good safety. However, it remained unknown whether 23BB as a drug candidate could offer renal protective effect against rhabdomyolysis-induced AKI. In the present study, we investigated the effect of 23BB in a murine model of glycerol (GL) injection-induced rhabdomyolysis. Following GL injection, the mice developed severe AKI as indicated by acute renal dysfunction and histologic changes, accompanied by increased HDAC6 expression in the cytoplasm of tubular epithelial cells. Pharmacological inhibition of HDAC6 by 23BB pretreatment significantly reduced serum creatinine and serum blood urea nitrogen (BUN) levels as well as attenuated renal tubular damage in GL-injured kidneys. HDAC6 inhibition also resulted in reduced TdT-mediated dUTP nick-end labeling (TUNEL)-positive tubular cells, suppressed BAX, BAK, cleaved caspase-3 levels, and preserved Bcl-2 expression, indicating that 23BB exerted potent renoprotective effects by the regulation of tubular cell apoptosis. Moreover, GL-induced kidney injury triggered multiple signal mediators of endoplasmic reticulum (ER) stress including GRP78, CHOP, IRE1α, p-eIF2α, ATF4, XBP1, p-JNK, and caspase-12. Oral administration of 23BB improved above-mentioned responses in injured kidney tissues and suggested that 23BB modulated tubular cell apoptosis via the inactivation of ER stress. Overall, these data highlighted that renal protection of novel HDAC6 inhibitor 23BB is substantiated by the reduction of ER stress-mediated apoptosis in tubular epithelial cells of rhabdomyolysis-induced AKI.

Sharp eyespot, caused by the necrotrophic fungal pathogen Rhizoctonia cerealis, is a devastating disease of bread wheat (Triticum aestivum). However, the molecular mechanisms underlying wheat defense against Rhizoctonia cerealis are still largely unknown. In this study, we identified a novel cysteine-rich receptor-like kinase (CRK)-encoding gene, designated as TaCRK3, through comparative transcriptomic analysis, and investigated its defence role against Rhizoctonia cerealis. TaCRK3 transcriptional abundance was significantly elevated by R. cerealis and exogenous ethylene treatments. Silencing of TaCRK3 significantly compromised resistance to R. cerealis and repressed expression of an ethylene biosynthesis enzyme-encoding gene ACO2 and a subset of defence-associated genes in wheat, whose transcript levels are up-regulated by ethylene stimulus. TaCRK3 protein was localized at the plasma membrane in wheat. Noticeably, both the heterologously-expressing TaCRK3 protein and its partial peptide harboring two DUF26 domains could inhibit growth of R. cerealis mycelia. These results suggest that the TaCRK3 mediates wheat resistance to R. cerealis through direct-antifungal activity and heightening the expression of defence-associated genes in the ethylene signaling pathway, and that its DUF26 domains are required for the antifungal activity of TaCRK3. This study provides a promising gene for breeding wheat varieties with resistance to R. cerealis.

These findings suggest that in skeletally immature patients with AIS, hybrid instrumentation cannot effectively prevent occurrence of the crankshaft phenomenon, whereas interval and consecutive pedicle screw instrumentation may be more (and equally) efficacious in this regard.