Liposome is one of the most commonly used drug delivery systems in the world, due to its excellent biocompatibility, satisfactory ability in controlling drug release, and passive targeting capability. However, some drawbacks limit the application of liposomes in clinical, such as problems in transporting, storing, and difficulties in maintaining the drug concentration in the local area. Scaffolds usually are used as implants to supply certain mechanical supporting to the defective area or utilized as diagnosis and imaging methods. But, in general, unmodified scaffolds show limited abilities in promoting tissue regeneration and treating diseases. Therefore, liposome-scaffold composite systems are designed to take advantages of both liposomes' biocompatibility and scaffolds' strength to provide a novel system that is more suitable for clinical applications. This review introduces and discusses different types of liposomes and scaffolds, and also the application of liposome-scaffold composite systems in different diseases, such as cancer, diabetes, skin-related diseases, infection and human immunodeficiency virus, and in tissue regeneration like bone, teeth, spinal cord and wound healing.Journal Pre-proof Drug-loaded liposomesLiposomes have been widely investigated as drug carriers, from the approved amphotericin B liposome in 1990 to the successful Onivyde™ in 2015. As drug carriers, liposomes have several advantages, for instance, they can carry various types of drugs, specifically, the internal water core can load hydrophilic drugs and the bilayers can carry hydrophobic ones. Additionally, liposomes exhibit the ability in controlling the drug release and decreasing the side effect of drugs. Furthermore, liposomes also show advantages in low toxicity, non-immunogenic and biodegradability. The phospholipid bilayer can be regarded as satisfactory platforms that can be modified with diverse ligands to achieve the goal of targeting delivery. Furthermore, the stability and efficacy of biological products can also be improved by utilizing liposomes as vehicles. Delivering small molecule hydrophilic drugsSeveral methods, such as reverse evaporation, pH gradient, ammonium sulfate gradient and repeated freeze thawing, are usually applied in the process of preparing small hydrophilic drugs-loaded liposomes. For example, Takeuchi et al. [14] fabricated polyborane encapsulated liposomes though pH gradient or reverse-phase evaporation, then they found that for the encapsulation efficiency of the liposome Journal Pre-proof 6 prepared using the pH gradient was twice as high as that prepared, using reverse-phase evaporation. Additionally, they observed that boron concentration of the polyborane encapsulated liposomes prepared using the pH gradient achieved 110-150 μg/g of tumor tissue. Delivering small molecule hydrophobic drugsUsually the film dispersion method is one of the simplest ways to fabricate lipid drug-loaded liposomes. For example, Fu et al.[15] fabricated novel temperature-sensitive liposomes loading paclitaxel (PTX-...

Loading hydrogels with bioactive agents is an important method for expanding the functional application of hydrogels. However, how to improve the local administration and slow release of drugs from a hydrogel is a challenge when using hydrogels loaded with drugs. In this paper, we first developed adhesive liposomes (A-LIP) loaded with BMP-2. Then, we incorporated the A-LIP into PEG hydrogels based on the coordinated cross-linking principle of SH-PEG and Ag + , fabricating an injectable, antibacterial and self-healing multifunctional drug delivery system. The adhesive lipo-hydrogel (A-LIP-PEG) fabricated by mixing PEG hydrogels and adhesive liposomes can be locally injected into an osteoporotic fracture and bone marrow cavity, where A-LIP-PEG can release adhesive liposomes that adhere to the bone injury area and promote bone reconstruction. Based on the principle of electrostatic attraction, tissue nonspecific A-LIP were fabricated by grafting octadecylamine onto liposomes. Because of the coordination and crosslinking of thiolated polyethylene (SH-PEG) and Ag + , the A-LIP-PEG showed excellent injectability and self-healing properties; further, because of the presence of Ag + , the A-LIP-PEG showed effective inhibition of S. aureus and Escherichia coli. The liposomes released by the A-LIP-PEG were able to adhere to tissue. In vitro studies showed that A-LIP-PEG significantly promoted osteogenic differentiation and had no significant effect on cell proliferation. Compared with common lipo-hydrogel (LIP-PEG), the A-LIP-PEG had better tissue adhesion in vivo, which led to better osteogenic differentiation and faster local bone remodeling of osteoporotic fractures in rats. This research developed a novel hydrogel system with adhesive liposomes to expand the application of hydrogels.

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Inhibiting hypoxia-inducible factor (HIF)-1α activity has been proposed as a novel therapeutic target in LPS-induced sepsis syndrome. We have reported that tanshinone IIA (TIIA) can reduce LPS-induced lethality and lung injury in mice, but the precise mechanisms have not been fully described. Therefore, the present study investigated whether the protective effect of TIIA was related to the inhibition of LPS-induced HIF-1α expression and what mechanisms accounted for it. This study showed that TIIA pretreatment improved LPS-induced biochemical and cellular changes and reduced the production of inflammatory cytokines. Pretreatment with TIIA decreased LPS-induced HIF-1α expression in vivo and in vitro. TIIA did not affect the LPS-induced HIF-1α mRNA level but inhibited HIF-1α protein translation by the inhibition of the PI3K/AKT and MAPK pathways and related protein translational regulators, such as p70S6K1, S6 ribosomal protein, 4E-BP1, and eIF4E, and promoted HIF-1α protein degradation via the proteasomal pathway in LPS-stimulated macrophages. These observations partially explain the antiinflammatory effects of TIIA, which provides scientific basis for its application for the treatment of acute lung injury/acute respiratory distress syndrome or sepsis.

ObjectivesTo summarize recommendations of existing guidelines on the treatment of upper respiratory tract infections (URTIs) in children, and to assess the methodological quality of these guidelines.MethodsWe searched seven databases and web sites of relevant academic agencies. Evidence-based guidelines on pediatric URTIs were included. AGREE II was used to assess the quality of these guidelines. Two researchers selected guidelines independently and extracted information on publication years, institutions, target populations, recommendations, quality of evidence, and strength of recommendations. We compared the similarities and differences of recommendations and their strength. We also analyzed the reasons for variation.ResultsThirteen guidelines meeting our inclusion criteria were included. Huge differences existed among these 13 guidelines concerning the categorization of evidence and recommendations. Nearly all of these guidelines lacked the sufficient involvement of stake holders. Further, the applicability of these guidelines still needs to be improved. In terms of recommendations, penicillin and amoxicillin were suggested for group A streptococcal pharyngitis. Amoxicillin and amoxicillin-clavulanate were recommended for acute bacterial rhinosinusitis (ABRS). An observation of 2–3 days prior to antibiotic therapy initiation for mild acute otitis media (AOM) was recommended with amoxicillin as the suggested first choice agent. Direct evidence to support strong recommendations on the therapy for influenza is still lacking. In addition, the antimicrobial durations for pharyngitis and ABRS were still controversial. No consensus was reached for the onset of antibiotics for ABRS in children.ConclusionsFuture guidelines should use a consistent grading system for the quality of evidence and strength of recommendations. More effort needs to be paid to seek the preference of stake holders and to improve the applicability of guidelines. Further, there are still areas in pediatric URTIs that need more research.

In the era of intelligence and informatization, digital supply chain finance (DSCF) has become one of the important trends in the development of supply chain finance. With the gradual increase of DSCF suppliers and various requirements of small and medium-sized enterprises for suppliers in providing financing services, selecting the most suitable DSCF supplier is of great significance for most small and medium-sized enterprises to expand reproduction and improve competitiveness. To address such a decision-making problem, this paper proposes a new multi-expert multiple criteria decision-making model by integrating the Best Worst Method (BWM) and Additive Ratio ASsessment (ARAS) method under the hesitant fuzzy linguistic environment, in which the hesitant fuzzy linguistic BWM method is applied to determine the weights of criteria while the hesitant fuzzy linguistic ARAS method is proposed to rank the candidate suppliers. A case study is given to demonstrate the procedure of the proposed method for the selection of optimal DSCF suppliers, which shows the feasibility of the proposed method. Finally, sensitivity analysis and comparative analyses are provided to testify the applicability and superiority of the proposed method.

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