Acteoside relieves mesangial cell injury by regulating Th22 cell chemotaxis and proliferation in IgA nephropathy

The existing therapies of IgA nephropathy are unsatisfying. Acteoside, the main component of Rehmannia glutinosa with anti-inflammatory and anti-immune effects, can improve urinary protein excretion and immune disorder. Th22 cell is involved in IgA nephropathy progression. This study was determined to explore the effect of acteoside on mesangial injury underlying Th22 cell disorder in IgA nephropathy. Serum Th22 cells and urine total protein of patients with IgA nephropathy were measured before and after six months treatment of Rehmannia glutinosa acteoside or valsartan. Chemotactic assay and co-culture assay were performed to investigate the effect of acteoside on Th22 cell chemotaxis and differentiation. The expression of CCL20, CCL22 and CCL27 were analyzed. To explore the effect of acteoside on mesangial cell injury induced by inflammation, IL-1, IL-6, TNF-α and TGF-β1 were tested. Results showed that the proteinuria and Th22 lymphocytosis of patients with IgA nephropathy significantly improved after combination treatment of Rehmannia glutinosa acteoside and valsartan, compared with valsartan monotherapy. In vitro study further demonstrated that acteoside inhibit Th22 cell chemotaxis by suppressing the production of Th22 cell attractive chemokines, i.e., CCL20, CCL22 and CCL27. In addition, acteoside inhibited the Th22 cell proliferation. Co-culture assay proved that acteoside could relieve the overexpression of pro-inflammatory cytokines, and prevent the synthesis of TGF-β1. TGF-β1 level in mesangial cells was positively correlated with the Th22 cell. This research demonstrated that acteoside can alleviate mesangial cell inflammatory injury by modulating Th22 lymphocytes chemotaxis and proliferation.     

Vertebral Fractures After Discontinuation of Denosumab: A Post Hoc Analysis of the Randomized Placebo‐Controlled FREEDOM Trial and Its Extension

Denosumab reduces bone resorption and vertebral and nonvertebral fracture risk. Denosumab discontinuation increases bone turnover markers 3 months after a scheduled dose is omitted, reaching above‐baseline levels by 6 months, and decreases bone mineral density (BMD) to baseline levels by 12 months. We analyzed the risk of new or worsening vertebral fractures, especially multiple vertebral fractures, in participants who discontinued denosumab during the FREEDOM study or its Extension. Participants received ≥2 doses of denosumab or placebo Q6M, discontinued treatment, and stayed in the study ≥7 months after the last dose. Of 1001 participants who discontinued denosumab during FREEDOM or Extension, the vertebral fracture rate increased from 1.2 per 100 participant‐years during the on‐treatment period to 7.1, similar to participants who received and then discontinued placebo (n = 470; 8.5 per 100 participant‐years). Among participants with ≥1 off‐treatment vertebral fracture, the proportion with multiple (>1) was larger among those who discontinued denosumab (60.7%) than placebo (38.7%; p = 0.049), corresponding to a 3.4% and 2.2% risk of multiple vertebral fractures, respectively. The odds (95% confidence interval) of developing multiple vertebral fractures after stopping denosumab were 3.9 (2.1–7. 2) times higher in those with prior vertebral fractures, sustained before or during treatment, than those without, and 1.6 (1.3–1.9) times higher with each additional year of off‐treatment follow‐up; among participants with available off‐treatment total hip (TH) BMD measurements, the odds were 1.2 (1.1–1.3) times higher per 1% annualized TH BMD loss. The rates (per 100 participant‐years) of nonvertebral fractures during the off‐treatment period were similar (2.8, denosumab; 3.8, placebo). The vertebral fracture rate increased upon denosumab discontinuation to the level observed in untreated participants. A majority of participants who sustained a vertebral fracture after discontinuing denosumab had multiple vertebral fractures, with greatest risk in participants with a prior vertebral fracture. Therefore, patients who discontinue denosumab should rapidly transition to an alternative antiresorptive treatment. Clinicaltrails.gov : NCT00089791 (FREEDOM) and NCT00523341 (Extension). © 2017 American Society for Bone and Mineral Research.     

Cardiopulmonary,biomarkers, and vascular responses to acute hypoxia following cardiac transplantation

Previous studies have suggested good adaptation of cardiac transplant (CTx) recipients to exposure to a high altitude. No studies have investigated the cardiopulmonary and biomarker responses to acute hypoxic challenges following CTx. Thirty‐six CTx recipients and 17 age‐matched healthy controls (HC) were recruited. Sixteen (16) patients (42%) had cardiac allograft vasculopathy (CAV). Cardiopulmonary responses to maximal and submaximal exercise at 21% O₂, 20‐minutes hypoxia (11.5% O₂), and following a 10‐minute exposure to 11.5% O₂ using 30% of peak power output were completed. Vascular endothelial growth factor (VEGF), interleukin‐6 (IL‐6), suppression of tumorigenicity 2 (ST2) were measured at baseline and at peak stress. Endothelial peripheral function was assessed using near‐infrared spectroscopy. Compared with HC, CTx presented a lesser O₂ desaturation both at rest (?19.4 ± 6.8 [CTx] vs ?24.2 ± 6.0% O₂ [HC], P < 0.05) and following exercise (?23.2 ± 4.9 [CTx] vs ?26.2 ± 4.7% O₂ [HC], P < 0.05). CTx patients exhibited a significant decrease in peak oxygen uptake. IL‐6 and VEGF levels were significantly higher in CTx recipients in basal conditions but did not change in response to acute stress. CTx patients exhibit a favorable ventilatory and overall response to hypoxic stress. These data provide further insights on the good adaptability of CTx to exposure to high altitude.     

Effectiveness of various hip preservation treatments for non-traumatic osteonecrosis of the femoral head: A network meta-analysis of randomized controlled trials

Background

Non-traumatic osteonecrosis of the femoral head (ONFH) is a refractory osteonecrosis disease caused by an abnormal blood supply to bone tissue. However, therapeutic hip preservation strategies are diverse, and the therapeutic outcomes are not ideal.