POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes) is a multisystem disorder with a good long-term prognosis. In its dozens of clinical features, those with independent prognostic value are still not well characterized. We retrospectively included 362 patients with newly diagnosed POEMS syndrome at our institute from 2000 to 2015. On the basis of a randomized sample splitting, we first identified four baseline clinical variables, including age >50 years (hazards ratio (HR) 4.07, 95% confidence interval (CI) 1.41-11.76, P=0.009), pulmonary hypertension (HR 3.99, 95% CI 1.44-11.04, P=0.008), pleural effusion (HR 3.81, 95% CI 1.23-11.79, P=0.02) and estimated glomerular filtration rate <30 ml/min/1.73 m (HR 8.25, 95% CI 2.18-31.25, P=0.002), associated with inferior overall survival in the derivation cohort, with the use of multivariate Cox regression model. These factors were incorporated together to develop a prognostic nomogram. Concordance index calculation (0.727, 95% CI 0.601-0.853, P=0.018) and calibration curve plotting demonstrated its significant predictive and discriminatory capacity in the validation cohort. This nomogram could be a useful and convenient tool in clinical practice to evaluate individualized prognosis in patients with newly diagnosed POEMS syndrome.

Objective: To investigate the effects of overexpression of nuclear factor E2-related factor-2 (NRF2) on lung injury in rats exposed to paraquat (PQ) poisoning. Methods: A mifepristone (RU486)-inducible recombinant adenoviral vector carrying the human NRF2 gene (Ad-RUNRF2) was constructed and transfected via airway into the rats 7 days before the administration of RU486. Rats were orally challenged with PQ at 20 mg/kg 24 h after the injection of RU486. On days 0.5, 3 and 21 after PQ poisoning, the expressions of NRF2 and cytokines related to inflammation and oxidation in lung tissue were examined. Results: RU486 remarkably enhanced NRF2 mRNA and NRF2 protein levels in Ad-RUNRF2-transfected rats in a dose-dependent manner ( p < 0.01). PQ stimulated compensatory overexpression of NRF2, heme oxygenase 1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO-1) in lungs on days 0.5 and 3 after exposure ( p < 0.05), but depleted the expression of catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione (GSH), with an increased malondialdehyde (MDA) ( p < 0.05). However, pretreatment with Ad-RUNRF2 and RU486 strongly enhanced the expression levels of NRF2, HO-1, NQO-1, CAT and GSH-Px in the lungs of PQ intoxicated rats, with increased GSH and decreased MDA ( p < 0.05). Pretreatment with Ad-RUNRF2 and RU486 also strongly suppressed the PQ-induced activation of nuclear factor κB (NF-κB) and decreased the levels of tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). In addition, Ad-RUNRF2 and RU486 induction significantly reduced PQ-induced pathological changes in lungs and attenuated lung oedema and protein leakage caused by PQ ( p < 0.05). Conclusion: RU486-induced overexpression of NRF2 in lungs transfected with Ad-RUNRF2 can ameliorate PQ-induced lung injury by the activation of the NRF2-antioxidant response element (ARE) pathway.