Dissolving microneedles loaded with nimodipine for prevention of sleep disorders at a high altitude.

Sleep disorders are one of the most common acute reactions on the plateau, which can cause serious complications. However, there is no effective and safe treatment currently available. Nimodipine (NMD) is a dihydropyridine calcium channel blocker with neuroprotective and vasodilating activity, mainly used for the treatment of ischemic brain injury. Commercial oral or injectable NMD formulations are not a good option for central neuron diseases due to their poor brain delivery. In this study, nimodipine dissolving microneedles (NDMNs) were prepared for the prevention of sleep disorders caused by hypoxia. NDMNs were composed of NMD and polyvinyl pyrrolidone (PVP) K90 with a conical morphology and high rigidity. After administration of NDMNs on the back neck of mice, the concentration of NMD in the brain was significantly higher than that of oral medication as was confirmed by the fluorescent imaging on mouse models. NDMNs enhanced cognitive function, alleviated oxidative stress, and improved the sleep quality of mice with high-altitude sleep disorders. The blockage of calcium ion overloading may be an important modulation mechanism. NDMNs are a promising and user-friendly formulation for the prevention of high-altitude sleep disorders.

Risk Factors of Secondary Vertebral Compression Fracture After Percutaneous Vertebroplasty or Kyphoplasty: A Retrospective Study of 650 Patients.

BACKGROUND In this study, we aimed to investigate the risk factors contributing to secondary vertebral compression fractures (SVCF) in patients undergoing percutaneous vertebroplasty (PVP) or kyphoplasty (PKP) due to osteoporotic vertebral compression fracture (OVCF). MATERIAL AND METHODS Between January 2010 and December 2017, 650 patients with regular follow-up were identified and retrospectively analyzed in this study. Of these patients, 410 patients underwent PVP and 240 patients underwent PKP surgery. Patients were followed for 24 months on average, ranging from 6 months to 36 months follow-up. Possible risk factors screened for were age, gender, regional distribution, outdoor activity (ODA), bone mineral density (BMD), surgical methods (unilateral or bilateral), bone cement dose, bone cement leakage, chronic disease history, postoperative anti-osteoporosis treatment, and level of preoperative OVCF. Logistic regression analysis was applied to determine potential risk factors. RESULTS As a result, 102 patients (15.7%) suffered SVCF after PVP/PKP surgery at the last follow-up. Binary logistic regression model showed that older age increased the risk of developing SVCF [odds ratio (OR)=2.48, P=0.031] while high-level BMD (OR=0.31, P<0.001) and ODA (OR=0.38, P=0.001) decreased the risk. Binary logistic regression model showed the following: Logit (P)=1.03+0.91X1-1.18X2-0.97X3 (X1=age, OR=2.48, P=0.031; X2=BMD, OR=0.31, P<0.001; X3=ODA, OR=0.38, P=0.001). CONCLUSIONS In conclusion, older age and lower BMD were identified as risk factors of SVCF for OVCF patients following PVP/PKP surgery, whereas more ODA played a protective role in SVCF development.

Inhibitory Effect of 2R,3R-Dihydromyricetin on Biofilm Formation by Staphylococcus aureus.

The adherence and biofilm formation of Staphylococcus aureus on food contact surfaces are a major concern for the food industry. Development of antibiofilm agents from polyphenols has drawn much attention due to their potent activity. The present study explored the antibacterial and antibiofilm activities of 2R,3R-dihydromyricetin (DMY) against S. aureus ATCC 29213. It was found that DMY exerted excellent antibacterial and bactericidal properties against S. aureus with minimum inhibitory concentration and minimum bactericidal concentration values of 0.125 and 0.25 mg/mL, respectively. Crystal violet staining and 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide sodium salt reduction assay demonstrated that DMY significantly reduced the biofilm biomass of S. aureus and decreased the metabolic activity of biofilm cells. Micrographs of light microscope and scanning electron microscope confirmed that DMY inhibited the biofilm formation and caused a disintegration of the complex biofilm architecture. Moreover, DMY was highly efficient in reducing the number of sessile S. aureus cells adhered to stainless steel. These results suggested that DMY could have potential application to control S. aureus contamination in a food processing environment.

Development of pectin/chitosan-based electrospun biomimetic nanofiber membranes loaded with dihydromyricetin inclusion complexes for wound healing application.

Accidents and surgical procedures inevitably lead to wounds, presenting clinical challenges such as inflammation and microbial infections that impede the wound-healing process. This study aimed to address these challenges by developing a series of novel wound dressings known as electrospun biomimetic nanofiber membranes. These membranes were prepared using electrostatic spinning technique, incorporating hydroxypropyl-ß-cyclodextrin/dihydromyricetin inclusion complexes. The prepared electrospun biomimetic nanofiber membranes exhibited randomly arranged fiber morphology with average fiber diameters ranging from 200 to 400 nm, resembling the collagen fibers in the native skin. These membranes demonstrated excellent biocompatibility, hemocompatibility, surface hydrophilicity, and wettability, while also releasing dihydromyricetin in a sustained manner. In vitro testing revealed that these membranes, loaded with hydroxypropyl-ß-cyclodextrin/dihydromyricetin inclusion complexes, displayed higher antioxidant potential and inhibitory effects against Staphylococcus aureus and Escherichia coli. Furthermore, these membranes significantly reduced the M1 phenotypic transition in RAW264.7 cells, even when stimulated by lipopolysaccharides, effectively restoring M2 polarization, thereby shortening the inflammatory period. Additionally, the in vivo wound healing effects of these membranes were validated. In conclusion, this study introduces a promising nanofiber membrane with diverse biological properties that holds promise for addressing various crucial aspects of the wound-healing process.

Spatiotemporally sequential delivery of biomimetic liposomes potentiates glioma chemotherapy.

As one of the most challenging cancers, glioma still lacks efficient therapeutic treatment in clinics. The dilemmas of nanodrug-based therapies for glioma are due not only the limited permeability of the blood-brain barrier (BBB) but also the deficiency of targeting tumor lesions. Thus, spatiotemporally sequential delivery of therapeutics from BBB-crossing to glioma accumulation is considered a strategy to obtain better outcomes. Here, we developed a biomimetic chemotherapy nanodrug composed of the hybrid membrane envelope of U87 cell membranes and RAW264.7 cell membranes, and the core of paclitaxel (PTX)-loaded liposome (PTX@C-MMCL). In the research, PTX@C-MMCL showed superior ability to cross the BBB via RAW264.7 cell membranes and accurate targeting to the brain tumor lesions relying on the homotypic targeting capacity of U87 cell membranes. Furthermore, PTX@C-MMCL can maintain a prolonged circulation in vivo. Importantly, PTX@C-MMCL effectively inhibited the development of glioma. Conclusively, our biomimetic nanodrug holds great potential for brain tumor targeting therapy.

The promising application of hydrogel microneedles in medical application.

OBJECTIVES: Hydrogel microneedles are emerging, and promising microneedles mainly composed of swelling polymers. This review is intended to summarize the preparation materials, formation mechanisms, applications and existing problems of hydrogel microneedles. METHODS: We collected the literature on the materials, preparation and application of hydrogel microneedles in recent years, and summarized their mechanism and application in drugs delivery. KEY FINDINGS: Hydrogel microneedles have higher safety and capabilities of controlled drug release, and have been mainly used in tumour and diabetes treatment, as well as clinical monitoring. In recent years, hydrogel microneedles have shown great potential in drug delivery, and have played the role of whitening, anti-inflammatory and promoting healing. CONCLUSIONS: As an emerging drug delivery idea, hydrogel microneedles for drug delivery has gradually become a research hotspot. This review will provide a systematic vision for the favourable development of hydrogel microneedles and their promising application in medicine, especially drug delivery.

Multifunctional HNT@Fe3O4@PPy@DOX Nanoplatform for Effective Chemo-Photothermal Combination Therapy of Breast Cancer with MR Imaging.

Multifunctional nanoparticles for imaging and treatment in cancer are getting more and more attention recently. Herein, halloysite nanotubes (HNTs), natural clay nanotubes, are designed as multifunctional nanoplatform for targeted delivering photothermal therapy agents and chemotherapeutic drugs. Fe3O4 was anchored on the outer surfaces of HNTs and then doxorubicin (DOX) was loaded on the nanotubes. Afterward, a layer of polypyrrole (PPy), as photothermal agent, was wrapped on the tubes. The nanoplatform of HNT@Fe3O4@PPy@DOX can be guided to tumor tissue by an external magnetic field, and then performs chemo-photothermal combined therapy by 808 nm laser irradiation. HNT@Fe3O4@PPy@DOX shows the ability of T2-weighted magnetic resonance imaging, which could be considered as a promising application in magnetic targeting tumor therapy. In vitro and in vivo experiments demonstrate that HNTs nanoplatform has good biocompatibility and produces a strong antitumor effect trigged by near-infrared laser irradiation. The novel chemo-photothermal therapy nanoplatform based on HNTs may be developed as a multifunctional nanoparticle for imaging and therapy in breast cancer.

Novel Simvastatin-Loaded Nanoparticles Based on Cholic Acid-Core Star-Shaped PLGA for Breast Cancer Treatment.

A novel nanocarrier system of cholic acid (CA) core, star-shaped polymer consisting of poly(D,L-lactide-co-glycolide) (PLGA) was developed for sustained and controlled delivery of simvastatin for chemotherapy of breast adenocarcinoma. The star-shaped polymer CA-PLGA with three branch arms was synthesized successfully through the core-first approach. The simvastatin-loaded star-shaped CA-PLGA nanoparticles were prepared through a modified nanoprecipitation method. The data showed that the fluorescence star-shaped CA-PLGA nanoparticles could be internalized into MDA-MB-231 and MDA-MB-468 human breast cancer cells. The simvastatin-loaded star-shaped CA-PLGA nanoparticles achieved significantly higher level of cytotoxicity than pristine simvastatin and simvastatin-loaded linear PLGA nanoparticles. Moreover, the expression of the cell cycle protein cyclin D1 was dramatically inhibited by simvastatin in both cells, with simvastatin-loaded star-shaped CA-PLGA nanoparticles having the greatest effect. MDA-MB-231 xenograft tumor model on BALB/c nude mice showed that simvastatin-loaded star-shaped CA-PLGA nanoformulations could effectively inhibit the growth of tumor over a longer period of time than pristine simvastatin and simvastatin-loaded linear PLGA nanoformulations at the same dose. In agreement with these, the nuclear expression of proliferation marker Ki-67 in simvastatin-loaded star-shaped CA-PLGA nanoparticles group was reduced to a most extent among four groups through tumor frozen section immunohistochemistry. In conclusion, the star-shaped CA-PLGA polymers could serve as a novel polymeric nanocarrier for breast cancer chemotherapy.

[Clinical application of sinus floor elevation guided by cone-beam computer tomography].

PURPOSE: To investigate the value of using con-beam computer tomography (CBCT) to evaluate bone volume in the edentulous area of posterior maxilla, and guide sinus floor elevation. METHODS: Twenty eight patients who planed to receive dental implant in the posterior maxilla underwent CBCT scan. After analysis of residual bone height, 19 patients with 5-10 mm bone height below the sinus floor underwent transcrestal sinus floor elevation, while 7 patients with less than 5 mm bone height below the sinus floor underwent lateral window sinus floor elevation. The treatment outcomes were assessed postoperatively. RESULTS: CBCT detected bone deficiency in the posterior maxillary alveolar bone in 26 patients, mucus cyst of maxillary sinus in 1 patient and sinus septa in 2 patients. Nineteen patients underwent transcrestal sinus floor elevation, and 7 patients underwent lateral window sinus floor elevation. All patients completed final dental restorations, and the restorations achieved satisfactory function and esthetic. CONCLUSIONS: CBCT imaging plays an important role in determining bone quality in posterior maxilla and guiding sinus floor elevation. Supported by Social Undertakings Technological Innovation and Demonstration Program of Nantong City (HS2011035).

Co-delivery of chemotherapeutic drugs with vitamin E TPGS by porous PLGA nanoparticles for enhanced chemotherapy against multi-drug resistance.

We report a strategy to make use of poly(lactic-co-glycolic acid) nanoparticle (PLGA NPs) for co-delivery of docetaxel (DTX) as a model anticancer drug together with vitamin E TPGS. The latter plays a dual role as a pore-forming agent in the nanoparticles that may result in smaller particle size, higher drug encapsulation efficiency and faster drug release, and also as a bioactive agent that could inhibit P-glycoprotein to overcome multi-drug resistance of the cancer cells, The DTX-loaded PLGA NPs of 0, 10, 20 and 40% TPGS were prepared by the nanoprecipitation method and then characterized for their size and size distribution, surface morphology, physical status and encapsulation efficiency of the drug in the NPs. All four NPs were found of size ranged 100-120 nm and EE ranged 85-95% at drug loading level around 10%. The in vitro evaluation showed that the 48 h IC50 values of the free DTX and the DTX-loaded PLGA NPs of 0, 10, 20% TPGS were 2.619 and 0.474, 0.040, 0.009 µg/mL respectively, which means that the PLGA NPs formulation could be 5.57 fold effective than the free DTX and that the DTX-loaded PLGA NPs of 10 or 20% TPGS further be 11.85 and 52.7 fold effective than the DTX-loaded PLGA NPs of no TPGS (therefore, 66.0 and 284 fold effective than the free DTX). Xenograft tumor model and immunohistological staining analysis further confirmed the advantages of the strategy of co-delivery of anticancer drugs with TPGS by PLGA NPs.

[Clinical use of beta-tricalcium phosphate ceramics with patient's own bone in maxillary elevation with osteotome].

PURPOSE: To evaluate the clinical value of using the patient's autogenous bone mixed with beta-tricalcium phosphate ceramics(ß-TCP) for maxillary sinus lift with simultaneous implantation. METHODS: Patients with loss of posterior teeth and bone height of maxillary sinus floor between 4-10mm underwent internal sinus floor elevation, the proportion of bone to ß-TCP was 1:1 and the mixture was inserted into the sinus floor. All cases had simultaneously placed ITI implants.The final crown fabrication was taken 4-6 months after implanting. RESULTS: Twenty-one implants were inserted in 16 cases, the mean increase height was 4.2mm(2-6mm). There was clinical complaint of maxillary sinus inflammation in 1 case within 2 weeks, but the symptoms disappeared after antibiotic therapy. The remaining of 20 implants had no obvious complications. All implants had loaded for 32 months and were stable and well osseointegration on X-ray film. CONCLUSIONS: Maxillary sinus elevation with simultaneous implantation is an easy procedure. Implants can be stable for a long time.

[Finite element analysis of mechanical characteristics during retracting mandibular incisors through sliding mechanics].

PURPOSE: To analyze the mechanical characteristic changes of teeth and arch under different loading direction during retracting mandibular incisors through implant, simulating clinical loading system. METHODS: Three- dimensional finite element model, including brackets, archwire, crampable hooks and implants, was reconstructed. The force direction was determined by connecting the points in crampable hook and the center point of implant, and the force point and force direction were changed with the adjustment of the height of crampable hook and the height of implant. Then three-dimensional movement trend of teeth, stress distribution in periodontal membrane and the largest displacement of archwire nodes in each group were calculated and analyzed. SPSS13.0 software package was used for statistical analysis. RESULTS: It was found that the height of implant and the height of crampable hook were correlated with the movement of teeth and stress distribution in periodontal membrane (P<0.01). The movement trend of teeth in the condition of different height of implant and different height of crampable hook was illustrated as follows:(1)with the height increase of crampable hook, the movement trend of the central and lateral incisors varied from mesial lingual tipping to mesial labial tipping. However, canines tipped distally and lingually; the second premolars tipped mesially and lingually, and the first molar roots tipped distally and buccally with decreasing tipping angle. (2) The largest stress distribution in the whole arch was located in the labial apical one-third area of the lateral incisors, while that of canines and the first molars was located in the alveolar ridges and root bifurcations. CONCLUSIONS: These findings indicate that the different movement trend during retracting anterior teeth can be achieved through the adjustment of the height of crampable hook, and implant, anchorage can effectively control anterior movement of the posterior teeth. Supported by Research Fund of Bureau of Science and Technology of Nantong City (Grant No. S40023).