ABSTRACT
Multivalent ion cross-linking has been used to form hydrogels between sodium alginate (SA) and hyaluronic acid (HA) in previous studies. However, more stable and robust covalent cross-linking is rarely reported. Herein, we present a facile approach to fabricate a SA and HA hydrogel for wound dressings with injectable, good biocompatibility, and high ductility. HA was first reacted with ethylenediamine to graft an amino group. Then, it was cross-linked with oxidized SA with dialdehyde to form hydrogel networks. The dressing can effectively promote cell migration and wound healing. To increase the antibacterial property of the dressing, we successfully loaded tetracycline hydrochloride into the hydrogel as a model drug. The drug can be released slowly in the alkaline environment of chronic wounds, and the hydrogel releases drugs again in the more acidic environment with wound healing, achieving a long-term antibacterial effect. In addition, one-dimensional partial differential equations based on Fickian diffusion with time-varying diffusion coefficients and hydrogel thicknesses were used to model the entire complex drug release process and to predict drug release.
Subject(s)
Bandages , Hydrogels , Hydrogels/pharmacology , Anti-Bacterial Agents/pharmacology , Wound Healing , Tetracycline/pharmacology , Hyaluronic Acid/pharmacologyABSTRACT
Objective: Conversion therapy (surgical resection after chemotherapy) is a promising option for unresectable gastric cancer (GC) patients. Addition of anti-angiogenesis drug improves response to chemotherapy. Hence, this study explored the feasibility and efficacy of preoperative paclitaxel (PTX)/S1 chemotherapy combined with apatinib for unresectable GC. Methods: Thirty-one eligible patients with a single unresectable factor were enrolled in this multi-center, single-arm trial. Apatinib (500 mg qd) was administered continuously, while PTX (130 mg/m2) on day 1 and S1 (80 mg/m2) on day 1-14 were given every 3 weeks. The treatment was given for three cycles preoperatively, but the last cycle did not include apatinib. The primary objective measurements included R0 resection rate, objective response rate (ORR) and morbidity of preoperative treatment. Results: Among the 31 patients, 30 patients were evaluable for tumor response, the ORR to preoperative treatment was 73.3%. Eighteen of 30 patients underwent surgery, and R0 resection was achieved in 17 patients. The patients who underwent the conversion surgery had a superior OS compared with those who did not (3 years OS: 52.9 vs 8.3%, p = 0.001). The surgery was operated after apatinib had stopped for a median duration of 4 weeks. Neither anastomotic leakage nor wound healing complications was observed. No increased bleeding event was observed compared with historical data. During preoperative treatment, grade 3 or 4 toxicities were experienced by 58.1% of the patients. Conclusion: Chemotherapy in combination with apatinib demonstrated higher rates of conversion and R0 resection and a superior survival benefit in initial unresectable GC. It is safe and reasonable to suspend apatinib for 4 weeks before the gastrectomy.
ABSTRACT
Nuclear energy development has entered an unexpected second nuclear era, which is mainly driven by developing countries. Despite major efforts to pursue a safe nuclear energy system in the first nuclear era, severe nuclear accidents occurred. A basic problem is that we do not have an adequate understanding of nuclear safety. From the viewpoints of risk and the close coupling of technical and social factors, this paper reexamines the nature of nuclear safety and reviews how previous experts understood it. We also highlight the new challenges that we are likely to confront in the unexpected second nuclear era and clarify some of the refinements that need to be made to the concept of nuclear safety from a sociotechnical perspective. These include the following: 1) Risk decisions should be made based on integrating social and technical elements (i.e., "social rationality"); 2) risk needs to be controlled based on the "Wuli-Shili-Renli" framework; 3) systems thinking should be substituted for reductionism in risk assessment, and social mechanisms need to be combined to address uncertainties; and 4) public-centered risk communication should be established. This contribution can provide a theoretical foundation for improving our understanding of the nature of nuclear safety and for transforming the concept of nuclear safety in the unexpected second nuclear era.