Pediatric Mandibular Reconstruction With Free Serratus Anterior-Rib Composite Flap: A Case Report.

ABSTRACT: Reconstruction of children's mandibles after mandibular resection for benign or malignant tumors is challenging. Microvascular flap reconstruction is a common treatment option for restoring mandibular continuity after the resection of oral cavity neoplasms.We presented 2 cases of childhood mandibular reconstruction after tumor wide excision and segmental mandibulectomy, one for malignant cancer and one for benign ossifying fibroma, with serratus-rib composite free flap. All 2 patients had a favorable facial profile, functional outcome, and dental occlusion at the last follow-up. The development of children's mandible and donor site needs to be considered compared with adult's mandibular reconstruction. Given its reliability and utility, this flap can be an alternative for pediatric mandibular reconstruction compared with the free fibular flap and other candidates.

The Preventive Effect of A Magnetic Nanoparticle-Modified Root Canal Sealer on Persistent Apical Periodontitis.

Persistent apical periodontitis is a critical challenge for endodontists. Developing root canal filling materials with continuous antibacterial effects and tightly sealed root canals are essential strategies to avoid the failure of root canal therapy and prevent persistent apical periodontitis. We modified the EndoREZ root canal sealer with the antibacterial material dimethylaminododecyl methacrylate (DMADDM) and magnetic nanoparticles (MNPs). The mechanical properties of the modified root canal sealer were tested. The biocompatibility of this sealer was verified in vitro and in vivo. Multispecies biofilms were constructed to assess the antibacterial effects of the modified root canal sealer. We applied magnetic fields and examined the extent of root canal sealer penetration in vitro and in vivo. The results showed that EndoREZ sealer containing 2.5% DMADDM and 1% MNP had biological safety and apical sealing ability. In addition, the modified sealer could increase the sealer penetration range and exert significant antibacterial effects on multispecies biofilms under an external magnetic field. According to the in vivo study, the apices of the root canals with the sealer containing 2.5% DMADDM and 1% MNP showed no significant resorption and exhibited only a slight increase in the periodontal ligament space, with a good inhibitory effect on persistent apical periodontitis.

Impact of submandibular gland preservation in neck management of early-stage buccal squamous cell carcinoma on locoregional control and disease-specific survival.

BACKGROUND: The feasibility of submandibular gland (SMG) preservation in oral squamous cell carcinoma (SCC) has occasionally been analyzed, but the differences in survival associated with the presence or absence of SMG preservation remain unknown. We aimed to prospectively evaluate the oncologic results of SMG preservation in cT1-2 N0 buccal SCC. METHODS: This was a prospective, non-randomized cohort study. Patients with surgically treated cT1-2 N0 buccal SCC were prospectively enrolled and divided into two groups based on the management of the SMG. Level 1b lymph nodes were categorized into six groups based on the positional relationship between the lymph node and the SMG. The main study endpoints were locoregional control (LRC) and disease-specific survival (DSS). RESULTS: A total of 31 of the 137 included patients underwent SMG-sparing neck dissection. Patients with SMG preservation were likely to be young persons. Superior metastasis occurred in 11 patients with a prevalence of 8.0%, followed by an anterior metastasis rate of 5.1%, and no metastases developed deeply or within the SMG. The 5-year LRC rates in the SMG-sparing and SMG-excision groups were 74 and 75%, respectively, and the difference was not significant (p = 0.970). The 5-year DSS rates in the SMG-sparing and SMG-excision groups were 74 and 69%, respectively, and the difference was not significant (p = 0.709). CONCLUSIONS: SMG involvement was rare, and the superior group carried the highest risk for lymph node metastasis. SMG-sparing neck dissection is selectively suggested in cT1-2 N0 buccal SCC patients, and could avoid postoperative asymmetric appearance and dry mouth.

Oncologic outcome of marginal mandibulectomy in squamous cell carcinoma of the lower gingiva.

BACKGROUND: There is a large amount of controversy about the best management of the mandible in oral squamous cell carcinoma (SCC), mainly owing to the inability to acquire accurate bone invasion status. Therefore, our goal was to analyse the oncologic safety in patients undergoing marginal mandibulectomy (MM) for cT1-2 N0 SCC of the lower gingiva. METHODS: Patients undergoing MM for untreated cT1-2 N0 SCC of the lower gingiva were retrospectively enrolled. The main endpoints of interest were locoregional control (LRC) and disease-specific survival (DSS). RESULTS: A total of 142 patients were included in the analysis, and a pathologic positive node was noted in 27 patients. Cortical invasion was reported in 23 patients, and medullary invasion was reported in 9 patients. The 5-year LRC and DSS rates were 85 and 88%, respectively. Patients with bone invasion had a significantly higher risk for recurrence than patients without bone invasion. However, the DSS was similar in patients with versus without bone invasion. Patients with a high neutrophil lymphocyte ratio had a higher risk for worse prognosis. CONCLUSIONS: The oncologic outcome in patients undergoing MM for cT1-2 N0 SCC of the lower gingiva was favourable; bone invasion was not uncommon, but it significantly decreased the prognosis in patients undergoing MM.

Polyethylene Glycol-Functionalized Magnetic Fe3O4/P(MMA-AA) Composite Nanoparticles Enhancing Efficient Capture of Circulating Tumor Cells.

Circulating tumor cells (CTCs) played a significant role in early diagnosis and prognosis of carcinomas, and efficient capture of CTCs was highly desired to provide important and reliable evidence for clinical diagnosis. In present work, we successfully synthesized functional magnetic Fe3O4/P(MMA-AA) composite nanoparticles (FCNPs) inspired by a counterbalance concept for recognition and capture of CTCs. This counterbalance, composed of polyethylene glycol (PEG) suppressing cell adhesion and anti-epithelial-cell-adhesion-molecule (anti-EpCAM) antibody targeting tumor cells, could both enhance the specific capture of tumor cells and reduce unspecific adhesion of normal cells. The study showed that the PEG density on the surface of the FCNPs affected the specificity of the materials, and a density of ca. 15% was efficient for reducing the unspecific adhesion. After incubation with the mixture of HepG2 cells and Jurkat T cells, the FCNPs reached a capture efficiency as high as about 86.5% of the cancer cells, suggesting great potential on detection of CTCs in the diagnoses and prognoses of cancer metastasis.

Effects of Pore Size on the Osteoconductivity and Mechanical Properties of Calcium Phosphate Cement in a Rabbit Model.

Calcium phosphate cement (CPC) porous scaffold is widely used as a suitable bone substitute to repair bone defect, but the optimal pore size is unclear yet. The current study aimed to evaluate the effect of different pore sizes on the processing of bone formation in repairing segmental bone defect of rabbits using CPC porous scaffolds. Three kinds of CPC porous scaffolds with 5 mm diameters and 12 mm length were prepared with the same porosity but different pore sizes (Group A: 200-300 µm, Group B: 300-450 µm, Group C: 450-600 µm, respectively). Twelve millimeter segmental bone defects were created in the middle of the radius bone and filled with different kinds of CPC cylindrical scaffolds. After 4, 12, and 24 weeks, alkaline phosphatase (ALP), histological assessment, and mechanical properties evaluation were performed in all three groups. After 4 weeks, ALP activity increased in all groups but was highest in Group A with smallest pore size. The new bone formation within the scaffolds was not obvious in all groups. After 12 weeks, the new bone formation within the scaffolds was obvious in each group and highest in Group A. At 24 weeks, no significant difference in new bone formation was observed among different groups. Besides the osteoconductive effect, Group A with smallest pore size also had the best mechanical properties in vivo at 12 weeks. We demonstrate that pore size has a significant effect on the osteoconductivity and mechanical properties of calcium phosphate cement porous scaffold in vivo. Small pore size favors the bone formation in the early stage and may be more suitable for repairing segmental bone defect in vivo.

Anti-Bacteria and Microecosystem-Regulating Effects of Dental Implant Coated with Dimethylaminododecyl Methacrylate.

The effects of dimethylaminododecyl methacrylate (DMADDM) modified titanium implants on bacterial activity and microbial ecosystem of saliva-derived biofilm were investigated for the first time. Titanium discs were coated with DMADDM solutions at mass fractions of 0 mg/mL (control), 1, 5 and 10 mg/mL, respectively. Biomass accumulation and metabolic activity of biofilms were tested using crystal violet assay and MTT (3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. 16S rRNA gene sequencing was performed to measure the microbial community. Live/dead staining and scanning electron microscopy (SEM) were used to value the structure of biofilm. The results showed that the higher mass fraction of DMADDM the coating solution had, the significantly lower the values of metabolic activity and accumulated biofilms got, as well as fewer live cells and less extracellular matrix. Moreover, 5 mg/mL of DMADDM was the most effective concentration, as well as 10 mg/mL. In microecosystem-regulation, the DMADDM modified titanium implant decreased the relative abundance of Neisseria and Actinomyces and increased the relative abundance of Lactobacillus, a probiotic for peri-implant diseases. In conclusion, via inhibiting growth and regulating microecosystem of biofilm, this novel titanium implant coating with DMADDM was promising in preventing peri-implant disease in an 'ecological manner'.

Hollow superparamagnetic PLGA/Fe3O4 composite microspheres for lysozyme adsorption.

Uniform hollow superparamagnetic poly(lactic-co-glycolic acid) (PLGA)/Fe(3)O(4) composite microspheres composed of an inner cavity, PLGA inner shell and Fe(3)O(4) outer shell have been synthesized by a modified oil-in-water (O/W) emulsion-solvent evaporation method using Fe(3)O(4) nanoparticles as a particulate emulsifier. The obtained composite microspheres with an average diameter of 2.5 µm showed excellent monodispersity and stability in aqueous medium, strong magnetic responsiveness, high magnetite content (>68%), high saturation magnetization (58 emu g(-1)) and high efficiency in lysozyme adsorption.

Reduced length of intensive care unit stay and early mechanical ventilator weaning with enhanced recovery after surgery (ERAS) in free fibula flap surgery.

This study aimed to evaluate the effects of the enhanced recovery after surgery (ERAS) program on postoperative recovery of patients who underwent free fibula flap surgery for mandibular reconstruction. This retrospective study included 188 patients who underwent free fibula flap surgery for complex mandibular and soft tissue defects between January 2011 and December 2022. We divided them into two groups: the ERAS group, consisting of 36 patients who were treated according to the ERAS program introduced from 2021 to 2022. Propensity score matching was used for the non-ERAS group, which comprised 36 cases selected from 152 patients between 2011 and 2020, based on age, sex, and smoking history. After propensity score matching, the ERAS and non-ERAS groups included 36 patients each. The primary outcome was the length of intensive care unit (ICU) stay; the secondary outcomes were flap complications, unplanned reoperation, 30-day readmission, postoperative ventilator use length, surgical site infections, incidence of delirium within ICU, lower-limb comorbidities, and morbidity parameters. There were no significant differences in the demographic characteristics of the patients. However, the ERAS group showed the lower length of intensive care unit stay (ERAS vs non-ERAS: 8.66 ± 3.90 days vs. 11.64 ± 5.42 days, P = 0.003) and post-operative ventilator use days (ERAS vs non-ERAS: 1.08 ± 0.28 days vs. 2.03 ± 1.05 days, P < 0.001). Other secondary outcomes were not significantly different between the two groups. Additionally, patients in the ERAS group had lower postoperative morbidity parameters, such as postoperative nausea, vomiting, urinary tract infections, and pulmonary complications (P = 0.042). The ERAS program could be beneficial and safe for patients undergoing free fibula flap surgery for mandibular reconstruction, thereby improving their recovery and not increasing flap complications and 30-day readmission.

Pro-endothelialization of nitinol alloy cardiovascular stents enhanced by the programmed assembly of exosomes and endothelial affinity peptide.

Stent implantation is one of the most effective methods for the treatment of atherosclerosis. Nitinol stent is a type of stent with good biocompatibility and relatively mature development; however, it cannot effectively achieve long-term anticoagulation and early endothelialization. In this study, nitinol surfaces with the programmed assembly of heparin, exosomes from endothelial cells, and endothelial affinity peptide (REDV) were fabricated through layer-by-layer assembly technology and click-chemistry, and then exosomes/REDV-modified nitinol interface (ACC-Exo-REDV) was prepared. ACC-Exo-REDV could promote the rapid proliferation and adhesion of endothelial cells and achieve anticoagulant function in the blood. Besides, ACC-Exo-REDV had excellent anti-inflammatory properties and played a positive role in the transformation of macrophage from the pro-inflammatory to anti-inflammatory phenotype. Ex vivo and in vivo experiments demonstrated the effectiveness of ACC-Exo-REDV in preventing thrombosis and hyperplasia formation. Hence, the programmed assembly of exosome interface could contribute to endothelialization and have potential application on the cardiovascular surface modification to prevent stent thrombosis and restenosis.

Refining and in-situ growth of polyaniline endows the cellulose fibers with electrical stimulation sterilization.

Bacteria and virus infections have posed a great threat to public health and personnel safety. For realizing rapid sterilization of the bacteria and virus, electrical stimulation sterilization was adopted to endow cellulose fibers with instantaneous antibacterial and antiviral properties. In the proposed strategy, the fiber is fluffed by mechanical refining, and then by means of the hydrogen bond between hydroxyl and aniline, the polyaniline (PANI) directionally grows vertically along the fine fibers via in-situ oxidative polymerization. Benefiting from the conductive polyaniline nanorod arrays on the fiber stem, the paper made from PANI modified refined fibers (PANI/BCF/P) exhibited excellent antibacterial and antiviral activity, the inhibition rates against S. aureus, E. coli, and bacteriophage MS2 can up to 100 %, 100 %, and 99.89 %, respectively when a weak voltage (2.5 V) was applied within 20 min. This study provides a feasible path for plant fiber to achieve efficient antibacterial and antiviral activity with electrical stimulation, which is of great significance for the preparation of electroactive antibacterial and antiviral green health products.

Enhancing plant fiber antibacterial and antiviral performance through synergistic action of amino and sulfonic acid groups.

As the most abundant renewable resource, cellulose fibers are potential candidates for use in health-protective clothing. Herein, we demonstrate a novel strategy for preparing cellulose fiber with prominent antibacterial and antiviral performance by the synergistic effect of amino groups and sulfonic acid groups. Specifically, guanylated chitosan oligosaccharide (GCOS) and N-sulfopropyl chitosan oligosaccharide (SCOS) were synthesized and chemically grafted onto cellulose fibers (CFs) to endow the fibers with antibacterial and antiviral properties. Moreover, a compounding strategy was applied to make the fibers with simultaneously high antibacterial and antiviral activity, especially in short contact time. The bacteriostatic rate (against S. aureus: 95.81 %, against E. coli: 92.07 %, 1 h) of the compounded fibers improved substantially when a few GCOS-CFs were mixed with SCOS-CFs; especially, it was much higher than both the individual GCOS-CFs and SCOS-CFs. By contrast, the improvement of the antiviral properties was less dramatic; however, even a few SCOS-CFs was mixed, the antiviral properties increased pronouncedly. Although the electrostatic interaction between SCOS and GCOS can make the SCOS-GCOS mixture lose some extent of antibacterial activity, the long chains of cellulose restrain the electrostatic interaction between sulfonic and amino groups, leading to their synergistic action and eventually superior antibacterial and antiviral effects.

Coxsackievirus A10 impairs nail regeneration and induces onychomadesis by mimicking DKK1 to attenuate Wnt signaling.

Coxsackievirus A10 (CV-A10) infection, a prominent cause of childhood hand-foot-and-mouth disease (HFMD), frequently manifests with the intriguing phenomenon of onychomadesis, characterized by nail shedding. However, the underlying mechanism is elusive. Here, we found that CV-A10 infection in mice could suppress Wnt/ß-catenin signaling by restraining LDL receptor-related protein 6 (LRP6) phosphorylation and ß-catenin accumulation and lead to onychomadesis. Mechanistically, CV-A10 mimics Dickkopf-related protein 1 (DKK1) to interact with Kringle-containing transmembrane protein 1 (KRM1), the CV-A10 cellular receptor. We further found that Wnt agonist (GSK3ß inhibitor) CHIR99021 can restore nail stem cell differentiation and protect against nail shedding. These findings provide novel insights into the pathogenesis of CV-A10 and related viruses in onychomadesis and guide prognosis assessment and clinical treatment of the disease.

Effects of a Novel Magnetic Nanomaterial on Oral Biofilms.

Dental caries is one of the most common oral chronic infectious diseases, and novel antibacterial materials must be developed to control plaque and inhibit formation of dental caries. Combining magnetic nanomaterials with antibacterial agents to decrease the formation of bacterial biofilm has been a hot topic in the biomedical field. The present study developed a novel magnetic nanomaterial chemically combined with dimethylaminododecyl methacrylate (DMADDM) and initially investigated its inhibiting effects on biofilms by using traditional caries-related bacteria and saliva flora models. The novel magnetic nanomaterials successfully loaded DMADDM according to thermogravimetric analysis, Fourier transform infrared spectroscopy, x-ray diffraction, vibrating sample magnetometry, scanning electron microscopy, and transmission electron microscopy results. Further, the novel nanoparticle Fe3O4@SiO2@DMADDM with concentration of 8 mg/mL could effectively reduce Streptococcus mutans biofilm and decrease the production of lactic acid. The 16S rDNA sequencing revealed that Fe3O4@SiO2@DMADDM could depress the proportion of caries-related bacteria in saliva-derived biofilm, such as Streptococcus, Veillonella, and Neisseria. Therefore, Fe3O4@SiO2@DMADDM is a novel effective antibacterial magnetic nanomaterial and has clinical potential in plaque control and dental caries prevention.

Enhancement of chondrocyte autophagy is an early response in the degenerative cartilage of the temporomandibular joint to biomechanical dental stimulation.

Autophagy is a cell protective mechanism for maintaining cellular homeostasis. The present study aimed to investigate whether autophagy is enhanced in the biomechanically induced degenerative cartilage of the temporomandibular joint (TMJ) and the potential role of mitogen-activated protein kinase kinase kinase kinase 3 (MAP4K3) and mammalian Target of rapamycin (mTOR) in this observation. To induce degenerative changes in the TMJs, rats were subjected to biomechanical dental stimulation by moving 4 molars away from their original position as we previously reported. The ultrastructure of autophagosome was observed by transmission electron microscopy. The number of lysosomes was analyzed by flow cytometry. The expression levels of Beclin1 and LC3 and the involvement of MAP4K3 activity were detected by immunohistochemistry, real-time PCR and western blot. The activity of the mTOR pathway indicated by p-mTOR and p-p70S6 K was assayed by western blot. TMJ degeneration, characterized by irregular cell arrangement and cell-free area, was induced in the experimental groups. Under transmission electron microscopy, we observed the presence of autophagosomes, small patches of condensed chromatin, abundant rough endoplasmic reticulum and Golgi apparatus. The number of lysosomes and the expression levels of Beclin1 and LC3 increased, while the activity of mTOR and the expression level of MAP4K3 decreased in the experimental groups. Cartilage in TMJ which was induced to be degenerative biomechanically exhibited autophagy accompanied by reduced mTOR and MAP4K3 activity.

Semisynthetic lipidated LC3 protein mediates membrane fusion.

All together: Lipidated LC3 has been synthesized by expressed protein ligation. A TEV-cleavable MBP tag was employed to facilitate ligation under folding conditions and to solubilize the lipidated protein. The synthetic LC3-phosphatidylethanolamine (PE) mediates membrane tethering and fusion at the physiological concentration of PE, and could be a useful tool for autophagy studies.

CT and MRI of radiation-induced sarcomas of the head and neck following radiotherapy for nasopharyngeal carcinoma.

AIM: To investigate the radiological findings of head and neck radiation-induced sarcomas (RISs) following radiotherapy for nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Fifty-nine patients with RISs were identified. Imaging characteristics on computed tomography (CT) and magnetic resonance imaging (MRI), including lesion location, extent, size, margin, internal architecture, pattern, and degree of enhancement, together with patient characteristics at NPC diagnosis and latency periods, were reviewed. RESULTS: The study included 20 women and 39 men, with a median age of 49 years (range 30-71 years). The median latency was 9 years (range 3-37 years). The median radiation dose at the site of RIS was 66 Gy (range 44-78 Gy). The most common histological RIS types were fibrosarcoma (44.1%) and osteosarcoma (30.5%). The most common RIS sites were the paranasal sinuses and the nasal cavity (39%), the neck (16.9%), and the mandible (15.3%). The mean size was 5.1 cm (range 1.2-8.6 cm). Overall, 78% of lesions extended to adjacent spaces and 66.1% were accompanied by bone destruction. Heterogeneous density/signal intensity before and after enhancement was seen in all lesions on imaging. Marked lesion enhancement was noted in 49 cases (76.3%). CONCLUSIONS: The radiologist should be aware of the different sites at which RISs occur and the radiological appearance of the wide variety of RIS subtypes. Careful imaging follow-up is necessary for early detection of RISs in patients with NPC after radiotherapy.

Tough and antibacterial poly(l-lactic acid) composites prepared via blending with the bifunctional macromolecular ionomer.

In order to expand the application of PLLA in the packaging field, improving its toughness and antibacterial activity has been widely concerned. However, seldom researches can simultaneously efficiently improve the toughness and antibacterial activity of PLLA by adding one kind of additions. To address above problems, the bifunctional branched poly(butylene adipate) ionomer additive (b-PBAUi) was synthesized. For b-PBAUi, its branched structure not only increased the plasticizing effect of additive, but also acted as reaction sites to introduce more antibacterial ionic salt. Due to the special structure of b-PBAUi, PLLA/b-PBAUi blends achieved excellent toughness and antibacterial efficiency. The elongation of blend reached 125 % even by adding 5 wt% b-PBAUi, which was 10 times higher than that of PLLA. From the analysis of phase morphology, it could be found that the microvoids promoting tensile yielding was the main tensile toughening mechanism for PLLA/b-PBAUi blends. In addition, the antibacterial activity of PLLA was significantly improved by adding b-PBAUi. For PLLA/b-PBAUi10 and PLLA/b-PBAUi15, the antibacterial efficiency against E. coli and S. aureus bacteria exceeded 99.0 %. By comprehensive consideration, the optimal blend ratio was achieved by PLLA/b-PBAUi10 due to its excellent toughness and antibacterial efficiency.

Spatial-Drug-Laden Protease-Activatable M1 Macrophage System Targets Lung Metastasis and Potentiates Antitumor Immunity.

Lung metastasis is a critical cause of cancer mortality and its therapy is largely challenged by the limited drug delivery efficiency and robust immunosuppression in metastatic tumors. Herein, we designed a spatial-drug-laden M1 macrophage system with liposomal R848 inside and fibroblast activation protein protease (FAP)-sensitive phospholipid-DM4 conjugate on the membrane of M1 macrophage (RDM). RDM could preferentially accumulate at the metastatic lesions in lungs and responsively release the therapeutic agents as free drug molecules or drug-loaded nanovesicles. RDM treatment notably enhanced the infiltration of CD3+CD8+ T cells to lung metastasis and, respectively, caused an 8.54-, 12.87- and 2.85-fold improvement of the granzyme-B-, interferon-γ-, and Ki67-positive subtypes versus negative control. Moreover, RDM treatment produced a 90.99% inhibition of lung metastasis in 4T1 models and significant prolongation of survival in three murine lung metastatic models. Therefore, the drug-laden FAP-sensitive M1 macrophage system represents a feasible strategy to target lung metastasis and boost antitumor immunity for antimetastasis therapy.

Hybrid Extracellular Vesicles-Liposomes Camouflaged Magnetic Vesicles Cooperating with Bioorthogonal Click Chemistry for High-Efficient Melanoma Circulating Tumor Cells Enrichment.

The capture of melanoma circulating tumor cells (melanoma CTCs, MelCTCs) is of great significance for the early diagnosis and personalized treatment of melanoma. The rarity and heterogeneity of MelCTCs have greatly limited the development of MelCTCs capture methods, especially those based on immune/aptamer-affinity. Herein, an extracellular vesicles-camouflaged strategy is designed to functionalize the magnetic nanoparticles (Fe3 O4 ) and to generate magnetic vesicles (Fe3 O4 @lip/ev) with excellent antifouling and active tumor cell targeting properties. Combined with the bioorthogonal click chemistry, the engineered magnetic vesicles with dibenzocyclooctyne can be widely used to target and separate all the metabolically labeled CTCs with varied phenotypes, organ origin, and even the biological species. The capture efficiency exceeded 80% with an extremely low detection limitation of ten cells. Most importantly, the strategy proposed can be directly applied to enrich MelCTCs from 0.5 mL blood samples of melanoma-bearing mice, with a greatly minimized residue of white blood cells (only 21-568) while ignoring the fluctuations of MelCTC phenotype.