Efficacy of pegfilgrastim to support neoadjuvant dose-dense epirubicin and cyclophosphamide chemotherapy in breast cancer.

PURPOSE: The role of long-acting hematopoietic growth factor in supporting dose-dense chemotherapy and minimizing hematologic toxicity has not been established. We investigated the efficacy and safety of once-per-cycle pegfilgrastim in breast cancer patients receiving neoadjuvant dose-dense epirubicin and cyclophosphamide (ddEC). METHODS: Newly diagnosed stage I to III breast cancer patients received four cycles of ddEC (E, 100 mg/m2 and C, 600 mg/m2 every 2 weeks) and 6 mg of subcutaneous pegfilgrastim on day 2 of each cycle. The primary endpoint was to evaluate the incidence of chemotherapy delay. Secondary endpoints include the incidences of febrile neutropenia (FN) and grade 3/4 neutropenia during the four ddEC cycles. RESULTS: A total of 240 patients were enrolled and 913 ddEC cycles were administered in the study. Chemotherapy delay occurred in 15 patients (6.3% of patients, 95% CI 3.2-9.4%) for 17 cycles (1.9% of cycles, 95% CI 1.0-2.8%). The most frequent cause of chemotherapy delay was transaminase elevation (10 patients, 12 cycles). A total of 12 patients (5.0%, 95% CI 2.2-7.8%) developed 13 episodes of FN. Of the 221 patients that completed four ddEC cycles with pegfilgrastim support, 209 patients (94.6%, 95% CI 91.6-97.6%) had a 100% relative dose intensity (RDI). A RDI ≥ 85% was achieved in 217 of 221 patients (98.2%, 95% CI 96.5-99.9%). Bone pain of any grade was recorded in 85 of 220 evaluable patients (38.6%, 95% CI 32.2-45.0%). CONCLUSIONS: Pegfilgrastim is effective and safe in facilitating four cycles of neoadjuvant ddEC, with low incidences of chemotherapy delay and febrile neutropenia.

Variations of odorous VOCs detected by different assessors via gas chromatography coupled with mass spectrometry and olfactory detection port (ODP) system.

Odorous volatile organic compounds (VOCs) were analysed via a thermal desorption gas chromatograph coupled with a mass spectrometer and olfactory detection port (TD-GC-MS/ODP) to characterize odour emissions from a wastewater treatment plant (WWTP). Three trained ODP assessors, screened according to the European dynamic olfactometry standard (EN: 13725), were used for the olfactory analysis. Their sensitivity to n-butanol varied within the acceptable limits. VOC samples from the WWTP were collected onto Tenax TA sorbent tubes in triplicate and each assessor analysed one tube in the same sample desorbing and analysing conditions. Intensities of odours detected from ODP were scaled from 1 to 4. The ODP assessors used their own odour descriptors based on their own experience as well as referenced descriptors on published compost and wastewater odour wheels. The ODP assessors detected a total of 32 different odorous VOCs; however, the intensities assigned by each assessor to particular VOCs varied. Moreover, some odorous VOCs were not detected by all assessors. For example, geosmin was detected by only two assessors. The use of a TD-GC-MS/ODP system for the analysis of odorous VOCs is valuable when analysed by different assessors, allowing a range of responses to specific odorants in a populations to be investigated.

A pH-neutral bioactive glass coated 3D-printed porous Ti6Al4V scaffold with enhanced osseointegration.

Osseointegration is vital for the success of non-degradable implants like those made of titanium alloys. In order to promote osseointegration, implants are made porous, providing space for bone ingrowth. Despite extensive optimization of the pore geometry and porosity, bone ingrowth into implants is still marginal; further modification to promote bone ingrowth as well as osseointegration becomes paramount. In this study, a pH neutral bioactive glass with the composition of 10.8% P2O5-54.2% SiO2-35% CaO (mol%; hereinafter referred to as PSC) was successfully coated on 3D-printed porous Ti6Al4V scaffolds using an in situ sol-gel method. This PSC coating is strongly bonded to the substrate and quickly induces the formation of hydroxyapatite on the scaffold surface upon contact with body fluid. In vitro, the PSC-coated Ti6Al4V scaffolds showed superior biocompatibility, cell proliferation promotion, cell adhesion, osteogenic differentiation and mineralization compared to their bare counterparts, implying better osseointegration. In vivo experiments confirmed this expectation; after being implanted, the coated scaffolds had more bone ingrowth and osseointegration, and consequently, higher push-out strength was achieved, proving the validity of the proposed concept in this study. In conclusion, PSC coating on 3D-printed porous Ti6Al4V scaffolds can improve osteogenesis, bone ingrowth, and osseointegration. Together with the versatility of this in situ sol-gel coating method, titanium alloy implants with better biological performances may be developed for immediate clinical applications.

Effects of exogenous cellulose-degrading bacteria on humus formation and bacterial community stability during composting.

This study aimed to reveal the potential mechanism of influence exogenous cellulose-degrading bacteria (ECDB) exerted on humus synthesis during the co-composting of corn straw and cattle manure. By measuring the changes in physicochemical factors and bacterial communities, it was revealed that inoculation with ECDB enhanced the driving force of cellulose degradation and humus synthesis. ECDB not only directly participated in cellulose degradation as degrading bacteria, but also changed the bacterial community succession, and increased the abundance of bacterial communities associated with cellulose degradation. The results showed that ECDB stimulated the potential functions and interactions of bacterial communities. Structural equation modeling confirmed that ECDB acted mainly as a bioactivator to promote humus formation in co-composting of corn straw and cattle manure. Taken together, these findings offered new strategies which can be effectively utilized to increase the efficiency and quality of corn straw composting.

[Mechanical properties and effect on osteodifferentiation of induced pluripotent stem cells of chitosan/whisker/calcium phosphate cement composite biomaterial].

Objective: To investigate the mechanical properties of the novel compound calcium phosphate cement (CPC) biological material as well as the biological activity and osteogenesis effects of induced pluripotent stem cells (iPS) seeding on scaffold and compare their bone regeneration efficacy in cranial defects in rats. Methods: Ac- cording to the different scaffold materials, the experiment was divided into 4 groups: pure CPC scaffold group (group A), CPC∶10% wt chitosan as 2∶1 ratio mixed scaffold group (group B), CPC∶10% wt chitosan∶whisker as 2∶1∶1 ratio mixed scaffold group (group C), and CPC∶10% wt chitosan∶whisker as 2∶1∶2 ratio mixed scaffold group (group D). Mechanical properties (bending strength, work-of-fracture, hardness, and modulus of elasticity) of each scaffold were detected. The scaffolds were cultured with fifth generation iPS-mesenchymal stem cells (MSCs), and the absorbance ( A) values of each group were detected at 1, 3, 7, and 14 days by cell counting kit 8 (CCK-8) method; the alkaline phosphatase (ALP) activity, Live/Dead fluorescence staining and quantitative detection, ALP, Runx2, collagen typeⅠ, osteocalcin (OC), and bone morphogenetic protein 2 (BMP-2) gene expressions by RT-PCR were detected at 1, 7, and 14 days; and the alizarin red staining were detected at 1, 7, 14, and 21 days. Twenty-four 3-month-old male Sprague Dawley rats were used to establish the 8 mm-long skull bone defect model, and were randomly divided into 4 groups ( n=6); 4 kinds of scaffold materials were implanted respectively. After 8 weeks, HE staining was used to observe the repair of bone defects and to detect the percentage of new bone volume and the density of neovascularization. Results: The bending strength, work-of-fracture, hardness, and modulus of elasticity in groups B, C, and D were significantly higher than those in group A, and in groups C, D than in group B, and in group D than in group C ( P<0.05). CCK-8 assay showed that cell activity gradually increased with the increase of culture time, the A values in groups B, C, and D at 3, 7, 14 days were signifiantly higher than those in group A, and in groups C, D than in group B ( P<0.05), but no significant difference was found between groups C and D ( P>0.05). Live/Dead fluorescence staining showed that the proportion of living cells in groups B, C, and D at 7 and 14 days was significantly higher than that in group A ( P<0.05), and in groups C, D at 7 days than in group B ( P<0.05); but no significant difference was found between groups C and D ( P>0.05). RT-PCR showed that the relative expressions of genes in groups B, C, and D at 7 and 14 days were significantly higher than those in group A, and in groups C, D than in group B ( P<0.05); but no significant difference was found between groups C and D ( P>0.05). Alizarin red staining showed that the red calcium deposition on the surface of scaffolds gradually deepened and thickened with the prolongation of culture time; the A values in groups B, C, and D at 14 and 21 days were significantly higher than those in group A ( P<0.05), and in groups C and D than in group B ( P<0.05), but no significant difference was found between groups C and D ( P>0.05). In vivo repair experiments in animals showed that the new bone in each group was mainly filled with the space of scaffold material. Osteoblasts and neovascularization were surrounded by new bone tissue in the matrix, and osteoblasts were arranged on the new bone boundary. The new bone in groups B, C, and D increased significantly when compared with group A, and the new bone in groups C and D was significantly higher than that in group B. The percentage of new bone volume and the density of neovascularization in groups B, C, and D were significantly higher than those in group A, and in groups C and D than in group B ( P<0.05); but no significant difference was found between groups C and D ( P>0.05). Conclusion: The mechanical properties of the new reinforced composite scaffold made from composite chitosan, whisker, and CPC are obviously better than that of pure CPC scaffold material, which can meet the mechanical properties of cortical bone and cancellous bone. iPS-MSCs is attaching and proliferating on the new reinforced composite scaffold material, and the repair effect of bone tissue is good. It can meet the biological and osteogenic activity requirements of the implant materials in the bone defect repair.