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Hypertrophic scars (HS) still remain an urgent challenge in the medical community. Traditional Chinese medicine (TCM) has unique advantages in the treatment of HS. However, due to the natural barrier of the skin, it is difficult for the natural active components of TCM to more effectively penetrate the skin and exert therapeutic effects. Therefore, the development of an efficient drug delivery system to facilitate enhanced transdermal absorption of TCM becomes imperative for its clinical application. In this study, we designed a compound Salvia miltiorrhiza–Blumea balsamiferananoemulsion gel (CSB-NEG) and investigated its therapeutic effects on rabbit HS models. The prescription of CSB-NEG was optimized by single-factor, pseudoternary phase diagram, and central composite design experiments. The results showed that the average particle size and PDI of the optimized CSB-NE were 46.0 ± 0.2 nm and 0.222 ± 0.004, respectively, and the encapsulation efficiency of total phenolic acid was 93.37 ± 2.56%. CSB-NEG demonstrated excellent stability and skin permeation in vitroand displayed a significantly enhanced ability to inhibit scar formation compared to the CSB physical mixture in vivo. After 3 weeks of CSB-NEG treatment, the scar appeared to be flat, pink, and flexible. Furthermore, this treatment also resulted in a decrease in the levels of the collagen I/III ratio and TGF-ß1and Smad2 proteins while simultaneously promoting the growth and remodeling of microvessels. These findings suggest that CSB-NEG has the potential to effectively address the barrier properties of the skin and provide therapeutic benefits for HS, offering a new perspective for the prevention and treatment of HS.

To identify the general features of acquisition of drug-resistance genes in two multi-drug resistant Enterobacteriaceaestrains isolated from a single patient in China.

The dental operative microscope has been widely employed in the field of dentistry, particularly in endodontics and operative dentistry, resulting in significant advancements in the effectiveness of root canal therapy, endodontic surgery, and dental restoration. However, the improper use of this microscope continues to be common in clinical settings, primarily due to operators’ insufficient understanding and proficiency in both the features and established operating procedures of this equipment. In October 2019, Professor Jingping Liang, Vice Chairman of the Society of Cariology and Endodontology, Chinese Stomatological Association, organized a consensus meeting with Chinese experts in endodontics and operative dentistry. The objective of this meeting was to establish a standard operation procedure for the dental operative microscope. Subsequently, a consensus was reached and officially issued. Over the span of about four years, the content of this consensus has been further developed and improved through practical experience.

Recently, interest in tumor-targeted and site-specific drug release from nanoparticles as a means of drug delivery has increased. In this study, we report a smart nanosized micelle formed by hyaluronic acid (HA) conjugated with d-α-tocopherol succinate (TOS) using a disulfide bond as the linker (HA–SS–TOS, HSST). HSST micelles can specifically bind to the CD44 receptors that are overexpressed by cancer cells. The high levels of glutathione (GSH) in tumor cells selectively break the disulfide bond linker. This effect results in the synchronous release of the payload and a TOS fragment. These two components subsequently demonstrate synergetic anticancer activity. First, we demonstrate that drug release from HSST occurs rapidly in physiological high redox conditions and inside cancer cells. Significant GSH-triggered drug release was also observed in vivo. Furthermore, an in vivo biodistribution study indicated that the HSST micelles efficiently accumulated at the tumor sites, primarily due to an enhanced permeability and retention effect and the efficient binding to the cancer cells that overexpressed the CD44 receptor. Interestingly, the synchronous release of paclitaxel (PTX) and the TOS fragment from the PTX-loaded HSST caused synergetic tumor cell killing and tumor growth inhibition. Our work presents a useful candidate for a drug delivery system that can specifically accumulate at tumor tissue, selectively release its payload and a TOS fragment, and thus display a synergetic anticancer effect.

The development of multifunctional nanoplatforms based on magnetic nanoparticles (MNPs) has attracted increasing attention. MNPs especially exhibit excellent responsiveness under the guidance of an external magnetic field (MF), resulting in tumor-specific, targeted delivery. The behavior and magnetic-targeting efficiency of MNPs largely depend on their physiochemical properties, especially the particle size; however, the optimal size range may vary across the multiple bioapplications associated with multifunctional nanoparticles. The optimal size range of nanoparticles for external MF-mediated targeted delivery has rarely been reported. In this work, we synthesized a series of monodisperse Fe3O4nanoparticles with identical surface properties ranging in size from 10 to 310 nm, and we systematically investigated their behavior and MF-assisted antitumor efficacy. Our data indicated that smaller Fe3O4nanoparticles exhibited greater cellular internalization, while larger Fe3O4nanoparticles showed greater tumor accumulation. Larger Fe3O4nanoparticles exhibited stronger magnetic responsiveness both in vitro and in vivo, which could be used to further induce increased accumulation of nanoparticles and their payload (e.g., doxorubicin) into the tumor site under the guidance of an external MF. Our work demonstrated that larger Fe3O4nanoparticles, with a diameter of up to 310 nm, exhibited the best magnetic-targeting efficiency mediated by an external MF and the strongest antitumor efficacy from combination photothermal-chemotherapy. Our results could serve as a valuable reference for the future design of MNPs and their targeted delivery via the modulation of an external MF.

Both photothermal therapy (PTT) and photodynamic therapy (PDT) are phototherapeutic approaches, which have been widely investigated for cancer therapy mediated by an external light source. Here, a nanosystem presenting the synchronous PTT and PDT effect realized through one-step near-infrared (NIR) light irradiation is reported. This system was fabricated by conjugating indocyanine green (ICG) on hollow gold nanospheres (HAuNS) using branched-polyethylenimine (PEI, MW = 10 kDa) as optimal linker, which provided a high ICG payload as well as a covering layer with suitable thickness on HAuNS to maintain ICG fluorescence and reactive oxygen species (ROS) productivity. The resulting system (ICG-PEI-HAuNS) had the molar ratio of ICG:PEI:Au = 3:0.33:5. Compared with free ICG, ICG-PEI-HAuNS exhibited dramatically enhanced stability of ICG molecules and greater intratumoral accumulation. The conjugation of ICG caused significantly higher plasmon absorption of ICG-PEI-HAuNS in the NIR region compared with HAuNS alone, inducing remarkably enhanced photothermal conversion efficiency and synchronous photodynamic effect under NIR light irradiation. Interestingly, compared with PTT or PDT alone, synchronous PTT and PDT produced by ICG-PEI-HAuNS upon NIR light irradiation induced significantly stronger antitumor and metastasis inhibition effects both in vitro and in vivo, which might be a promising strategy for cancer treatment.

The development of multifunctional nanoparticles has attracted increasing attention. The versatility of nanoparticles largely depends on their physiochemical properties (especially size). However, the optimized size range may be different for the bioapplications of each function associated with multifunctional nanoparticles. It is important to investigate every optimized size range to ascertain which size enables the best function of the nanoparticles before deciding their final size. In this work, we synthesized a series of monodisperse Fe3O4nanoparticles with identical surface properties ranging in size from 60 to 310 nm and systematically investigated their biobehavior and application. Our data indicate that compared to their large counterparts, small Fe3O4nanoparticles exhibited greater cellular internalization and deeper penetration into multicellular spheroids, thus enabling a higher photothermal ablation efficacy in vitro. Interestingly, larger Fe3O4nanoparticles showed greater accumulation in tumors, thereby inducing more efficient tumor growth inhibition. In addition, 120 nm may be the optimal diameter of Fe3O4nanoparticles for magnetic resonance imaging and photoacoustic tomography in vitro. However, more efficient in vivo imaging mediated by Fe3O4nanoparticles will predominantly depend on their high accumulation. Our work presents a different appropriate size range for each biofunction of Fe3O4nanoparticles, which could be a valuable reference for future nanoparticle design.

This study aims to define an optimal dosage and to investigate the therapeutic effects of brucine dissolving microneedles (Bru-DMNs) on rheumatoid arthritis (RA). Composite PVP K30 and CS were selected as needle tip materials, single PVA as a backing material, and brucine (Bru) as the drug of this model. Bru-DMNs were successfully fabricated by a two-step centrifugation method. The DMNs produced satisfactory mechanical strength and biocompatibility, and the needle body was completely dissolved in approximately 10 min. After microneedle (MN) administration, the skin recovered to its original state within 6 h free of irritation. The transdermal test in vitro revealed that the skin transmittance of Bru could be significantly improved by MN administration. Drug load in the MN was released after 6 h, with cumulative permeability at 94.84%. To define the optimal dosage of Bru-DMNs for RA, the present study established an RA rat model and administered different concentrations of Bru solution or suspension. The optimal dosage of MN production (approximately 124.50 g/patch) was determined when Bru concentration was at 16 mg/mL. Further pharmacodynamics exploration revealed that drug loading MN effectively inhibited toe swelling of RA rats, reduced synovial hyperplasia due to articular cartilage erosion, and diminished swelling in the thymus and spleen. Network pharmacological analysis demonstrated that Bru might play a role in the RA treatment by regulating TNF-ɑ, IL-17and IL-1β. This regulation pathway was verified by ELISA and western blot assays.