Small extracellular vesicles derived from human mesenchymal stem cells prevent Th17-dominant neutrophilic airway inflammation via immunoregulation on Th17 cells.

Type 17 helper T cells (Th17)-dominant neutrophilic airway inflammation is critical in the pathogenesis of steroid-resistant airway inflammation such as severe asthma. Small extracellular vesicles (sEV) derived from human mesenchymal stem cells (MSCs) display extensive therapeutic effects and advantages in many diseases. However, the role of MSC-sEV in Th17-dominant neutrophilic airway inflammation and the related mechanisms are still poorly studied. Here we found that MSC-sEV significantly alleviated the infiltration of inflammatory cells in peribronchial interstitial tissues and reduced levels of inflammatory cells, especially neutrophils, in bronchoalveolar lavage fluids (BALF) of mice with neutrophilic airway inflammation. Consistently, MSC-sEV significantly decreased levels of IL-17A in BALF and Th17 in lung tissues. Furthermore, we found that labelled MSC-sEV were taken up by human CD4+ T cells most obviously at 12 h after incubation, and distributed mostly in mouse lungs. More importantly, potential signaling pathways involved in the MSC-sEV mediated inhibition of Th17 polarization were found using RNA sequencing. Using Western blot, JAK2-STAT3 pathway was identified as an important role in the inhibition of Th17 polarization by MSC-sEV. We found that proteins in MSC-sEV were mostly involved in the therapeutic effects of MSC-sEV. In total, our study suggested that MSC-sEV could be a potential therapeutic strategy for the treatment of neutrophilic airway inflammation.

17-Year Follow-up of Comparing Mastoscopic and Conventional Axillary Dissection in Breast Cancer: A Multicenter, Randomized Controlled Trial.

INTRODUCTION: Longer follow-up was necessary to determine the exact value of mastoscopic axillary lymph node dissection (MALND). METHODS: From January 1, 2003, to December 31, 2005, 1027 patients with breast cancer were randomly assigned to two groups: MALND and CALND (conventional axillary lymph node dissection); 996 eligible patients were enrolled. RESULTS: The final cohort of 996 patients was followed for an average of 198 months. Events other than death differed significantly between the two cohorts (p = 0.0311; 46.3% in MALND and 53.2% in CALND, respectively). The sum of events other than death and deaths from other causes was much higher in the CALND (59.6%) than MALND (53.4%) group (p = 0.0494). The 17-year disease-free survival DFS rates were 36.7% for the MALND and 33.6% for the CALND group, respectively. There was a significant difference between the groups (p = 0.0306). Overall survival (OS) rates were 53.2% after MALND and 46.0% after CALND (p = 0.0119). MALND patients had much less axillary pain (p = 0.0000), numbness or paresthesia (p = 0.0000), arm mobility (p = 0.0000) and arm swelling on the operated side (p = 0.0000). Aesthetic appearance of the axilla was much better in the MALND than CALND group (p = 0.0000) at an average follow-up of 17 years. CONCLUSIONS: The use of MALND in breast cancer surgery not only decreases the relapse and arm complications but also improves long-term survival of patients. Therefore, MALND should be one of the preferred approaches for breast cancer surgery when ALND is needed. TRIAL REGISTRATION INFORMATION: The comparison of long-term outcomes of mastoscopic and conventional axillary lymph node dissection in breast cancer: a multicenter randomized control trial. ChiCTR-TRC-11001477, CHiCTR. First registration 08/14/2011.

IL-33 receptor expression on myeloid and plasmacytoid dendritic cells after allergen challenge in patients with allergic rhinitis.

The diversity of immune responses in allergic diseases is critically mediated by dendritic cells (DCs), including myeloid and plasmacytoid DCs. Allergen inhalation increased the release of IL-33 from patients with allergic rhinitis (AR), which affecting the downstream cells by binding to its receptor (ST2). However, the effects of inhaled allergens on the expression of ST2 by DCs and IL-33 on the function of mDCs are unknown. The levels of ST2+mDCs and ST2+pDCs in the blood from patients with AR and healthy subjects were examined using flow cytometry. Moreover, the patients were challenged using the allergens and the levels of ST2+mDCs and ST2+pDCs were investigated at different time points. We found that there were higher levels of ST2+ mDCs and ST2+ pDCs in patients with AR, and these levels were further increased 0.5 h after allergen inhalation. Additionally, the type 2 immune response was upregulated after challenge. IL-33 treatment increased the expression of ST2 on mDCs. Our study demonstrated that ST2 was upregulated on DCs after allergen inhalation and that mDCs responded directly to IL-33 through ST2, suggesting that the IL-33/ST2 axis might play an important role in the pathogenesis of allergic rhinitis by DCs.

Advantage of Eu3+ -Doped Polystyrene Microspheres Compared with Colloidal Gold Used in Immunochromatographic Assays for the Detection of Melamine in Milk.

Colloidal gold and Eu3+ -doped fluorescent microspheres were applied as labels to develop the immunochromatographic strips for detecting melamine in milk. Under the optimized condition, the visual detection limit of colloidal gold-immunochromatographic test strip (ICTS) was 150 µg/L of melamine in phosphate-buffered saline (PBS), although the visual detection limit of fluorescent nanoparticles (FN)-ICTS was 75 µg/L in PBS. As thermal acceleration test, FN-ICTS could be stored at 37 °C for at least 11 d before sample testing, but the color of the lines on colloidal gold-ICTS faded away after 7-d storage. The visual result of FN-ICTS was more stable than that of colloidal gold-ICTS, and the fluorescence intensity of the line on FN-ICTS could be maintained up to 30 d at 22 °C after sample testing. Once the immunochromatographic strips were used to detect melamine in milk, no negative effect of milk components on the performance of FN-ICTS was identified, whereas the performance of colloidal gold-ICTS was significantly influenced by milk matrix.

Comparison of mastoscopic and conventional axillary lymph node dissection in breast cancer: long-term results from a randomized, multicenter trial.

OBJECTIVE: To compare the long-term results of mastoscopic axillary lymph node dissection (MALND) and conventional axillary lymph node dissection (CALND). PATIENTS AND METHODS: From January 1, 2003, through December 31, 2005, a group of 1027 consecutive patients with operable breast cancer were randomly assigned to 1 of 2 study groups: MALND and CALND. The median follow-up was 63 months. The primary end points of the study were operative outcomes, complication reduction, function conservation, and cosmetics. The secondary end points were disease-free and overall survival. RESULTS: The mean operative blood loss in the MALND group was less than in the CALND group (P<.001). The patients who underwent MALND had less axillary pain, numbness or paresthesias, and arm swelling (P<.001). The aesthetic appearance of the axilla in the MALND group was much better than that in the CALND group (P=.001 at 6 months and P=.002 at 24 months). A significant difference was found between the 2 groups in distant metastasis (P=.04). The disease-free survival rate was 64.5% in the MALND group and 60.8% in the CALND group (P=.88). The overall survival rate was 81.7% in the MALND group and 78.6% in the CALND group (P=.95). CONCLUSION: Compared with CALND, MALND has advantages in operative outcomes, complication reduction, function conservation, and cosmetics.