Moossvendsen1057

Graphical abstract.To investigate the beneficial effects of oridonin, a diterpenoid compound isolated from Rabdosia rubescens, on the inflammatory response in TNBS-induced post-inflammatory irritable bowel syndrome (PI-IBS) model and the underlying mechanism. Using the PI-IBS rat model and Caco-2 cell lines, we found that intestinal barrier function reflected by lactulose/mannitol (L/M) ratio and tight junction protein level was significantly ameliorated by oridonin. We also demonstrated that oridonin abrogated inflammation through inhibiting the phosphorylation of NF-κBp65 as well as its downstream gene (iNOS, COX-2, IL-1β, and IL-6) level. Molecular docking studies confirmed the good binding activity between oridonin and PXR. In Caco-2 cell lines, oridonin markedly inhibited LPS-induced NF-κB activation in a PXR-dependent manner. Meanwhile, PXR and its target genes CYP3A4 and P-gp were induced by oridonin, which was associated with the decreased expression of NF-κB and the recovery of intestinal barrier. This study indicated that the therapeutic effect of oridonin on experimental PI-IBS through repairing intestinal barrier function may be closely associated with the regulatory role of PXR/NF-κB signaling pathway. Oridonin may serve as a PXR ligand for the development of drugs in the therapy for PI-IBS.Botulinum toxin (BT) is used to treat a large number of muscle hyperactivity syndromes. Its use in dystonia, however, is still one of the most important indications for BT therapy. When BT is injected into dystonic muscles, it produces a peripheral paresis which is localised, well controllable and follows a distinct and predictable time course of around 3 months. Adverse effects are always transient and usually mild, long-term application is safe. With this profile BT can be used to treat cranial dystonia, cervical dystonia and limb dystonia including writer's and musician's cramps. The recent introduction of BT high dose therapy also allows to treat more wide-spread dystonia including segmental and generalised dystonia. BT can easily be combined with other anti-dystonic treatments such as deep brain stimulation and intrathecal baclofen application. Best treatment results are obtained when BT therapy is integrated in the multimodal and long-term 'multilayer concept of treatment of dystonia'. The biggest challenge for the future will be to deliver state of the art BT therapy to all dystonia patients in need, regardless of whether they live in developed countries or beyond.

Local excision might represent an alternative to total mesorectal excision for patients with locally advanced rectal cancer who achieve a major or complete clinical response after neoadjuvant chemoradiotherapy.

Between August 2005 and July 2011, 63 patients with mid-low rectal adenocarcinoma who had a major/complete clinical response after neoadjuvant chemoradiotherapy were enrolled in a multicenter prospective phase 2 trial and underwent transanal full thickness local excision. UNC 3230 datasheet The main endpoint of this study was to evaluate the 5- and 10-year overall, relapse-free, local, and distant relapse-free survival, which were calculated by applying the Kaplan-Meier method. The rate of patients with rectum preserved and without stoma were also calculated.

Of 63 patients, 38 (60%) were male and 25 (40%) were female, with a median (range) age of 64 (25-82) years. At baseline, the following clinical stages were found cT2, n = 21 (33.3%); cT3, n = 42 (66.6%), 39 (61.9%) patients were cN+. At a median (range) follow-up of 108 (32-166) months, the estimated cumulative 5- and 10-year overall survival, relapse-free survival, local recurrence-free survival, and distant recurrence-free survival were 87% (95% CI 76-93) and 79% (95% CI 66-87), 89% (95% CI 78-94) and 82% (95% CI 66-91), both 91% (95% CI 81-96), and 90% (95% CI 80-95) and 86% (95% CI 73-93), respectively. Overall, 49 (77.8%) patients had their rectum preserved, and 54 (84.1%) were stoma-free.

In highly selected patients, the local excision approach after neoadjuvant chemoradiotherapy is associated with excellent long-term outcomes, high rates of rectum preservation and absence of permanent stoma.

In highly selected patients, the local excision approach after neoadjuvant chemoradiotherapy is associated with excellent long-term outcomes, high rates of rectum preservation and absence of permanent stoma.

The purpose of this study was to identify factors associated with quality-of-life recovery after gastrectomy.

Patients anticipated to undergo gastric cancer resection were invited to complete the European Organisation for Research and Treatment of Cancer (EORTC) QLQ C30 and STO22 surveys in the preoperative setting and at 0-1.5months (early), > 1.5-6months (intermediate), and > 6-18months (late) following resection. Quality-of-life recovery was measured as paired differences between pre- and postoperative results. Multivariable linear regression identified factors associated with preoperative quality of life and degree of change following resection.

Across 393 participants, response rates at the intermediate and late postoperative time points were 58% (n = 228) and 71% (n = 277), respectively. Relative to baseline, median global health scale decreased in the early (- 15.1 pts, p < 0.001) and intermediate (- 3.6 pts, p = 0.02) time points, but recovered by the late time point (+ 1.2 pts, p = 0.411). Relative to distal/subtotal gastrectomy, proximal/total gastrectomy was associated with worse recovery in both the early and late time points. Surgical complications were associated with worse early recovery. Patients who presented with locally advanced tumors (T3-T4) had lower preoperative quality-of-life scores, and more readily recovered to baseline after surgery. A minimally invasive approach was not associated with postoperative recovery.

Most patients recover to baseline within 1year following major gastrectomy, and recovery is easier with more limited resections. Patients with locally advanced tumors tend to have poorer baseline quality of life, which may improve following resection.

Most patients recover to baseline within 1 year following major gastrectomy, and recovery is easier with more limited resections. Patients with locally advanced tumors tend to have poorer baseline quality of life, which may improve following resection.