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.

Drug-coated balloon for the treatment of small vessel disease: 9 months of angiographic results and 12 months of clinical outcomes of the PEPCAD China SVD study.

BACKGROUND: Whether the drug-coated balloons (DCBs)-alone strategy was superior to plain old balloon angioplasty (POBA) in treating SVD remains unknown. AIMS: We aimed to evaluate the efficacy and safety of DCBs for the treatment of coronary de novo small vessel disease (SVD) and provide further evidence for extending the clinical indications of DCBs. (ChiCTR1800014966). METHODS: Eligible patients were randomized at a 2:1 ratio to receive DCB treatment or POBA in this prospective, multicenter clinical trial. The reference vessel diameter of lesions was visually assessed to be 2.0 to 2.75 mm. The primary endpoint of the study was angiographic in-segment late luminal loss (LLL) at the 9-month follow-up to demonstrate the superiority of DCB treatment to POBA in SVD. The composite clinical endpoints included clinically driven target lesion revascularization (CD-TLR), target lesion failure (TLF), major adverse cardiac events (MACEs), and thrombosis at the 12-month follow-up. RESULTS: A total of 270 patients were enrolled (181 for DCB, 89 for POBA) at 18 centers in China. The primary endpoint of 9-month in-segment LLL in the intention-to-treat population was 0.10 ± 0.33 mm with DCB and 0.25 ± 0.38 mm with POBA (p = 0.0027). This difference indicated significant superiority of DCB treatment (95% CI: -0.22, -0.04, psuperiority = 0.0068). The rates of the clinical endpoints-CD-TLR, TLF, and MACEs-were comparable between groups. No thrombosis events were reported. CONCLUSIONS: DCB treatment of de novo SVD was superior to POBA with lower 9-month in-segment LLL. The rates of clinical events were comparable between the two devices.

Effects of different frequencies of Er:YAG laser on the bonding properties of zirconia ceramic.

The effects of Er:YAG laser with different frequencies on zirconia ceramic's bonding properties were studied. In total, 42 Y-TZP (yttrium-stabilized tetragonal zirconia polycrystals, UPCERA ST) with 3 mm × 3 mm × 2 mm divided into 6 groups (n = 7): control (C), sandblasting (SB), and Er:YAG laser (A1-A4), which the frequencies correspond to 5 Hz, 10 Hz, 15 Hz, and 20 Hz, IPS e.max Press ceramics were B. Scanning electron microscope (SEM) images were recorded. The ceramics were bonded to enamel from extracted teeth. After being constantly stored at 37 ℃ for 24 h, the shear test was performed with a universal testing machine. Stereomicroscope evaluated fracture modes. Stereomicroscope evaluated fracture modes. Data were analyzed by SPSS26.0 statistical software; the standard was P = 0.05. (1) The SEM showed the surface of A1-A4 became rough compared with C. (2) The shear test showed that the highest bonding strength for B was 13.15 ± 2.97 MPa, followed by SB was 7.78 ± 0.97 MPa, and A2 was 7.13 ± 0.75 MPa. However, there was no significant difference between SB and A2 (P > 0.05). Fracture modes of C were the interface fracture of Y-TZP and resin adhesive; most of A1-A4 and SB also were interface fracture, a few mixed fractures, and cohesion fracture of resin adhesive; B were all mixed fracture. Er:YAG laser with 10 Hz could be used as an alternative to sandblasting with Al2O3 for surface modification of Y-TZP to increase the bonding strength.

Two-year results and subgroup analyses of the PEPCAD China in-stent restenosis trial: A prospective, multicenter, randomized trial for the treatment of drug-eluting stent in-stent restenosis.

BACKGROUND: The PEPCAD China ISR trial investigated the safety and efficacy of paclitaxel-coated balloon (PCB) angioplasty in an Asian patient population with coronary drug-eluting stent in-stent restenosis (DES-ISR). METHODS: A total of 220 patients with coronary DES-ISR were treated with PCB angioplasty or with paclitaxel-eluting stents (PES). This randomized (1:1), single-blind prospective multicenter trial in a Chinese population used 9-month in-segment late lumen loss (LLL) as the primary endpoint. Secondary endpoints included the 24-month clinical event rates. RESULTS: Both treatment groups were similar in terms of patient, lesion, or procedural characteristics. After the 12-month follow-up evaluation, additional clinical events only occurred in the PES study group. The combined rate of all-cause mortality and myocardial infarction (MI) in the PCB group was significantly lower than that in the PES group (3.7% vs. 11.8%, P = 0.03). Additional subgroup analyses of 9-month in-segment LLL and 2-year target lesion failure in patients with diabetes, small vessels, diffuse ISR, and stent margin restenosis did not show more favorable results for one specific treatment group. CONCLUSIONS: The 2-year follow-up demonstrated sustained long-term clinical efficacy for both devices. PCB angioplasty was associated with significantly lower overall and cardiovascular mortality/MI rates in patients with DES-ISR lesions while avoiding the use of additional metal layers for drug release (ClinicalTrials.gov identifier: NCT 01622075).

Highly efficient co-removal of copper (II) and phthalic acid with self-synthesized polyamine resin.

A novel method was proposed for efficient co-removal of Cu (II) and phthalic acid (PA) using self-synthesized polyamine resin (R-NH(2)). The adsorption properties of R-NH(2) were thoroughly investigated by equilibrium, kinetic and dynamic tests in sole and binary systems at pH 5.0. The Freundlich model was a good fit for all the isotherm data, showing higher Kf values in the binary system than the sole system. The pseudo-second-order kinetic equation showed a better correlation to the experimental data in all cases and PA uptake was much faster than that of Cu (II). R-NH(2) showed highest adsorption capacities to both Cu (II) and PA among the five tested resins. Moreover, the presence of PA markedly enhanced the adsorption of Cu (II), being around 3.5 times of that of the sole system. The adsorption of PA was also slightly increased when Cu (II) was coexistent. Furthermore, using Fourier transform infrared spectrometry (FTIR) and species calculations, possible mechanisms were proposed that Cu (II) coordinated with -NH(2) and negative PA species interacted with -NH(3)(+) by electrostatic attraction. [Cu-PA] complex in the binary system possessed a much higher affinity than free Cu (II) to chelating with -NH(2), resulting in mutual enhancement.

Multihydrogen Bond Modulated Polyzwitterionic Removable Adhesive Hydrogel with Antibacterial and Hemostatic Function for Wound Healing.

Wound management is a major challenge worldwide, placing a huge financial burden on the government of every nation. Wound dressings that can protect wounds, accelerate healing, prevent infection, and avoid secondary damage continue to be a major focus of research in the health care and clinical communities. Herein, a novel zwitterionic polymer (LST) hydrogel incorporated with [2-(methacryloyloxy) ethyl] dimethyl-(3-sulfopropyl) ammonium hydroxide (SBMA), mussel-inspired N-[tris(hydroxymethyl)methyl] acrylamide (THMA), and lithium magnesium salt was prepared for functional wound dressings. The incorporation of the THMA monomer containing three hydroxyl groups gives the hydrogel suitable adhesion properties (∼6.0 KPa). This allows the LST zwitterionic hydrogels to bind well to the skin, which not only protects the wound and ensures its therapeutic efficacy but also allows for painless removal and reduced patient pain. Zwitterionic sulfobetaine units of SBMA provide antimicrobial and mechanical properties. The chemical structure and microscopic morphology of LST zwitterionic hydrogels were systematically studied, along with their swelling ratio, adhesion, and mechanical properties. The results showed that the LST zwitterionic hydrogels had a uniform and compact porous structure with the highest swelling and mechanical strain of 1607% and 1068.74%, respectively. The antibacterial rate of LST zwitterionic hydrogels was as high as 99.49%, and the hemostatic effect was about 1.5 times that of the commercial gelatin hemostatic sponges group. In further studies, a full-thickness mouse skin model was selected to evaluate the wound healing performance. Wounds covered by LST zwitterionic hydrogels had a complete epithelial reformation and new connective tissue, and its vascular regenerative capacity was increased to about 2.4 times that of the commercial group, and the wound could completely heal within 12-13 days. This study provides significant advances in the design and construction of multifunctional zwitterionic hydrogel adhesives and wound dressings.

[Experimental study on the stimulation effect of temperature and capsaicin on oral mucosa of rats].

PURPOSE: This study evaluated the effect of hot etching with two acid solutions on the surface topography and bond strength of zirconia. METHODS: Firstly, twenty-four pieces of zirconia with a size of 10 mm×10 mm×2 mm and 20 pieces of zirconia with a size of 3 mm×3 mm×2 mm were prepared. Then pieces were divided into four groups, and dealt with separately according to the following groups: no treatment (group A), sandblasting (group B), hot etching with HCl(group C), hot etching with HF(group D). Finally, the surface topography and bond strength were tested by atomic force microscopy(AFM), scanning electron microscope(SEM), X-ray diffraction(XRD) and universal testing machine, etc. Statistical analysis of the experimental data was performed with SPSS 26.0 software package. The final results of XRD were analyzed using MDI Jade 6 combined with Origin 2019 software. RESULTS: Groups C and D produced completely different topographical changes on the surface of zirconia than group B. Obvious interfacial cracks were observed in group B. Group D achieved the highest roughness value (78.17±4.94) nm and highest shear bond strength (25.09±4.09) MPa. CONCLUSIONS: Compared with HCl, hot etching with HF could achieve more uniform and dense porous morphology, greater roughness and shear bond strength. There were no obvious cross-section interfacial cracks and crystal phase transformations on the surface of zirconia.

[Effect of different frequencies of Er:YAG laser on bond properties of zirconia ceramic].

PURPOSE: The effect of different frequencies of Er:YAG laser on bond properties of zirconia ceramic was investigated. METHODS: 3 mm×3 mm ×2 mm Y-TZP blocks were randomly divided into 6 groups（n=5）：control group (C)，sandblasting group (SB) and Er:YAG laser group (A1-A4) in which the frequencies were 5, 10, 15 and 20 Hz, respectively, IPS e.max Press ceramics were used as group B. Scanning electron microscope (SEM) images were recorded for each group. The ceramics were bonded to teeth. After being stored in a constant temperature water bath at 37 ℃ for 24 hours, shear test was performed with universal testing machine. Fracture modes were evaluated with stereomicroscope. The data were analyzed with SPSS 26.0 software package. RESULTS：SEM showed that compared with the control group (C)，the surface of Y-TZP treated by Er:YAG laser with different frequencies became rough. The results of shear test showed that the highest bond strength value for IPS e.max Press ceramics group(B) was (13.15±2.97) MPa, followed by sandblasting group (SB): (7.78±0.97) MPa, and 10 Hz group (A2): (7.13±0.75) MPa. There was no significant difference between sandblasting group (SB) and 10Hz group(A2) (P>0.05). Fracture modes of the control group (C) were mainly interface fracture of Y-TZP and resin cement；most of the fracture modes of Er:YAG laser and sandblasting group (SB) were interface fracture of Y-TZP and resin cement，a few of mixed fracture and cohesion fracture of resin cement；and the fracture modes of IPS e.max Press ceramics group(B) were all mixed fracture. CONCLUSIONS：Er:YAG laser with 10 Hz can replace 110 µm Al2O3 sandblasting for surface modification of Y-TZP, in order to increase the bonding strength between Y-TZP and resin cement.

Design of Injectable Poly(γ-glutamic acid)/Chondroitin Sulfate Hydrogels with Mineralization Ability.

Biocompatible hydrogels are considered promising agents for application in bone tissue engineering. However, the design of reliable hydrogels with satisfactory injectability, mechanical strength, and a rapid biomineralization rate for bone regeneration remains challenging. Herein, injectable hydrogels are fabricated using hydrazide-modified poly(γ-glutamic acid) and oxidized chondroitin sulfate by combining acylhydrazone bonds and ionic bonding of carboxylic acid groups or sulfate groups with calcium ions (Ca2+). The resulting hydrogels display a fast gelation rate and good self-healing ability due to the acylhydrazone bonds. The introduction of Ca2+ at a moderate concentration enhances the mechanical strength of the hydrogels. The self-healing capacity of hydrogels is improved, with a healing efficiency of 87.5%, because the addition of Ca2+ accelerates the healing process of hydrogels. Moreover, the hydrogels can serve as a robust template for biomineralization. The mineralized hydrogels with increasing Ca2+ concentration exhibit rapid formation and high crystallization of apatite after immersion in simulated body fluid. The hydrogels containing the aldehyde groups possess good bioadhesion to the bone and cartilage tissues. With these superior properties, the developed hydrogels demonstrate potential applicability in bone tissue engineering.

Injectable poly(γ-glutamic acid)-based biodegradable hydrogels with tunable gelation rate and mechanical strength.

Polypeptide-based hydrogels have potential applications in polymer therapeutics and regenerative medicine. However, designing reliable polypeptide-based hydrogels with a rapid injection time and controllable stiffness for clinical applications remains a challenge. Herein, a class of injectable poly(γ-glutamic acid) (PGA)-based hydrogels were constructed using furfurylamine and tyramine-modified PGA (PGA-Fa-Tyr) and the crosslinker dimaleimide poly(ethylene glycol) (MAL-PEG-MAL), through a facile strategy combining enzymatic crosslinking and Diels-Alder (DA) reaction. The injectable hydrogels could be quickly gelatinized and the gelation time, ranging from 10 to 95 s, could be controlled by varying the hydrogen peroxide (H2O2) concentration. Compared with hydrogels formed by single enzymatic crosslinking, the compressive stress and strain of the injectable hydrogels were remarkably enhanced because of the occurrence of the subsequent DA reaction in the hydrogels, suggesting the DA network imparted an outstanding toughening effect on the hydrogels. Furthermore, the mechanical strength, swelling ratio, pore size, and degradation behavior of the injectable hydrogels could be easily controlled by changing the molar ratios of H2O2/Tyr or furan/maleimide. More importantly, injectable hydrogels encapsulating bovine serum albumin exhibited sustained release behavior. Thus, the developed hydrogels hold great potential for applications in biomedical fields, such as tissue engineering and cell/drug delivery.

Fabrication of stents with endothelial function in vitro.

OBJECTIVE: The aim of the study is to fabricate stents with rabbit outgrowth endothelial progenitor cells (OECs) to facilitate their endothelial function in vitro. METHODS: Rabbit OECs were isolated from peripheral blood and identified by immunofluorescence and flow cytometry. Cells proliferation and migration were measured by growth curve and modified Boyden chamber assay. Adhesion assay was performed by replating cells on fibronectin-coated dishes. VEGF, G-CSF and NO in supernatant were tested. OECs were poured on fibronectin-coated or uncoated stents. After six days, scanning electron microscopy (SEM) and inverted fluorescent microscopy observation were performed. RESULTS: About three to four weeks after culture, OECs were characterized as adherent cells which were double positive for Dil-acLDL uptake and FITC-UEA-I binding, with high expression of CD34. They also showed high ability of proliferation, adhesion and migration properties. Compared with uncoated stents, more OECs migrated and adhered onto fibronectin-coated stents. OECs seeding onto the fibronectin coated stents could secret more cytokine and NO. Endothelialization of coated stents was visible both under the SEM and inverted fluorescent microscope. CONCLUSIONS: OECs can differentiate to endothelial lineage and possess high ability of proliferation, migration and adhesion. It is feasible to fabricate OECs-seeded stents in vitro, while the stents coated with fibronectin facilitate this endothelialization process.

[Study on root canal variation of maxillary premolar and its relationship to maxillary sinus by cone-beam CT].

PURPOSE: To investigate the anatomic morphology of root and root canal system of maxillary premolars by using cone-beam computer tomography (CBCT), in order to provide imaging basis for clinical treatment. METHODS: CB CT images of 720 patients (aged from 18 to 67 years) were included. They were divided into 5 groups according to their ages：18-28，29-38，39-48，49-58 and＞58 years old . The number of roots and root canals, root canal configuration, the distance between two orifices,root canal curvature,distance from apex to maxillary sinus,symmetry of the bilateral teeth and its relationship to age changes were analyzed statistically using SPSS21.0 software package. RESULTS: Double root canal of the first maxillary premolar accounted the most (89.72%), and type IV was the frequent type (57.78%) . The incidence of single root canal in the second maxillary premolar (53.06%) was slightly higher than double root canal (46.94%). Root canal type was mainly type I (53.06%). There was symmetrical distribution in the bilateral root and root canals of maxillary premolars. The detection rate of the single root canal was changed with age, and the distance between the two orifice was closely related to the root morphology. The detection rate of root curvature in maxillary first and second premolar was 32.53% and 21.50% in buccolingual direction. There was a certain proportion of S-type complex root canal.16.69% of the maxillary second premolar and maxillary sinus were closely related (d≤0.05 mm). CONCLUSIONS: The anatomical structure of root and root canal is complicated .The prevalence of the bilateral teeth presents symmetry and age-related changes.The curvature of root canal is complex, and the roots are closely related to maxillary sinus.

Biomechanical Comparison of Expansive Pedicle Screw and Polymethylmethacrylate-augmented Pedicle Screw in Osteoporotic Synthetic Bone in Primary Implantation: An Experimental Study.

STUDY DESIGN: Expansive pedicle screws (EPS) and polymethylmethacrylate-augmented pedicle screws (PMMA-PS) were inserted into osteoporotic synthetic bones, which were then tested by radiographic and biomechanical examinations. OBJECTIVE: To compare the stability of EPS and PMMA-PS with that of a conventional pedicle screw (CPS) in an osteoporotic synthetic bone. SUMMARY OF BACKGROUND DATA: It is a significant challenge for orthopedic surgeons performing transpedicular fixation in the osteoporotic spine. Prior studies have suggested that both EPS and PMMA-PS can increase the screw stability effectively. However, there are no biomechanical comparisons of EPS and PMMA-PS, especially in primary spinal surgery in osteoporosis. METHODS: Thirty osteoporotic synthetic bone blocks were divided into 3 groups randomly. A pilot hole was prepared in advance in all samples by the same method. Then, the CPS was inserted directly into the pilot hole in the CPS group; the hole in the PMMA-PS group was first filled with polymethylmethacrylate (PMMA; 2.5 mL) and then inserted with CPS, and the EPS was inserted directly into the blocks in the EPS group. Twenty-four hours later, x-ray and computed tomography examination and axial pullout tests were performed on all samples; the block destructions were then recorded, and the hole diameters were measured. RESULTS: In the CPS group, the screw was surrounded directly by the synthetic bone without any other materials, whereas in the PMMA-PS group, the screw was totally wrapped up by PMMA, and the PMMA was evenly distributed in the synthetic bone around the screw, indicating obvious improvement of the local density around the track. In the EPS group, the anterior part of the EPS presented an obvious expansion in synthetic bone and formed an unguiform structure pressing the surrounding synthetic bone. Screw stabilities in both the PMMA-PS and the EPS groups were significantly enhanced compared with those in the CPS group, and the screw stability in the PMMA-PS group was significantly higher than that in the EPS group. After the pullout tests, the block destructions were the most severe in the PMMA-PS group and the lightest in the CPS group. Hole diameters in the PMMA-PS and the EPS groups were significantly larger than that in the CPS group, whereas the diameter of the hole in the PMMA-PS group was significantly greater than that in the EPS group. CONCLUSIONS: EPS can significantly increase the strength of screw fixation compared with CPS in osteoporotic synthetic bone. Although EPS shows a weaker fixation strength compared with PMMA-PS in the osteoporotic synthetic bone, it may still provide an alternative option to prevent screw loosening in the clinical treatment of osteoporosis.

Fermentation scale up for α-arbutin production by Xanthomonas BT-112.

α-Arbutin is a glycosylated hydroquinone that has an inhibitory function against tyrosinase. The aim of the present study is to develop an efficient and inexpensive method for large-scale production of α-arbutin by using Xanthomonas BT-112 as biocatalyst. To accomplish this goal, various surfactants were tested to enhance the α-arbutin production, and the optimal operational conditions for 30L jar fermenter were scaled up for a production level of 3000L with using a constant volumetric oxygen transfer coefficient (KLa) and the volumetric aeration rate per volume unit (Q/V) as scale-up criteria. Under the optimized conditions, the α-arbutin produced in the presence of 0.4% (w/v) Tween-80 was 124.8% higher than that of the control, and the yield of α-arbutin in 3000L fermenter was 38.2g/L with a molar conversion ratio of 93.7% based on the amount of hydroquinone supplied. This result is comparable to the results from laboratory-scale fermenter. Hence, 100-fold scale-up was successfully achieved.

Formulation and delivery of itraconazole to the brain using a nanolipid carrier system.

The objectives of this study were to develop and characterize itraconazole (ITZ)-loaded nanostructured lipid carriers (NLCs) and to study their potential for drug delivery into the brain. Precirol(®) ATO 5 and Transcutol(®) HP were selected as the lipid phase, and Tween(®) 80 and Solutol(®) HS15 as surfactants. The ITZ-NLCs were prepared by a hot and high-pressure homogenization method. The entrapment efficiency for the best formulation batch was analyzed using high-performance liquid chromatography and was found to be 70.5%±0.6%. The average size, zeta potential, and polydispersity index for the ITZ-NLCs used for animal studies were found to be 313.7±15.3 nm, -18.7±0.30 mV, and 0.562±0.070, respectively. Transmission electron microscopy confirmed that ITZ-NLCs were spherical in shape, with a size of less than 200 nm. Differential scanning calorimetry and X-ray diffractometry analysis showed that ITZ was encapsulated in the lipid matrix and present in the amorphous form. The in vitro release study showed that ITZ-NLCs achieved a sustained release, with cumulative release of 80.6%±5.3% up to 24 hours. An in vivo study showed that ITZ-NLCs could increase the ITZ concentration in the brain by almost twofold. These results suggest that ITZ-NLCs can be exploited as nanocarriers to achieve sustained release and brain-targeted delivery.

Characterization of osteogenically induced adipose tissue-derived precursor cells in 2-dimensional and 3-dimensional environments.

Earlier reports on a putative precursor cell population in adipose tissue showed differentiation along several mesodermal lineages, leading some to think that adipose tissue can be a source of cells applicable in regenerative medicine. However, characterizations of these adipose-derived precursor cells (ADPC) in the 3-dimensional (3-D) environment, especially within the area of bone-specific composite scaffolds, have been lacking. In this study, ADPC plated on culture flasks or seeded on medical grade polycaprolactone-tricalcium phosphate scaffolds (mPCL-CaP) were able to differentiate along the osteogenic lineages in both 2-D and 3-D environments as assessed with immunohistochemistry of osteo-related proteins, reverse transcriptase-polymerase chain reactions and alkaline phosphatase assay. The mPCL-CaP scaffolds provided adipose-derived cells (ADC) with a suitable environment as determined by DNA and metabolic assays, light, confocal and scanning electron microscopy. Flow cytometry revealed ADC to be CD29+, CD44+, CD73+, CD90+ and CD14-, CD31-, CD34-, CD45-, CD71-, and therefore showed the absence of hematopoietic stem cells but possibly the presence of pericytes and mescenchymal stem cells with osteogenic potential. The results of this study demonstrated the potential of using ADPC in combination with mPCL-CaP scaffolds for bone regenerative medicine.