Efficacy, mechanism, and safety of melatonin-loaded on thermosensitive nanogels for rabbit VX2 tumor embolization: A novel design.

Transarterial chemoembolization (TACE) has been widely used for hepatocellular carcinoma. Reducing hypoxia in the tumor microenvironment after TACE remains a challenge as tumor progression is common in post-TACE patients due to the hypoxic tumor microenvironment. In this study, melatonin loaded on p(N-isopropyl-acrylamide-co-butyl methylacrylate) (PIB-M) was used for tumor embolism. Two types of human hepatoma cell lines were used to explore the mechanism by which melatonin prevents the growth and metastasis of cancer cells in vitro. A VX2 rabbit tumor model was used to evaluate the efficacy, mechanism, and safety of PIB-M in vivo. We found that under hypoxic condition, melatonin could inhibit tumor cell proliferation and migration by targeting hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor A (VEGF-A) in vitro. In vivo, PIB-M inhibited tumor growth and metastasis in rabbit VX2 tumors by promoting apoptosis of tumor cells and targeting related angiogenic proteins and vascular permeability proteins. A high concentration of melatonin in the PIB-M group could be maintained in tumor tissue for 72 h after embolization. The liver and kidney functions were most damaged on the first day but recovered to normal on the seventh day after embolization in the PIB-M group. This novel method may open avenues for reduction of tumor growth and metastasis after TACE and is efficacy and safety, which may be used for treatment for other solid tumors and clinical translation.

Vertical Control of a Severe Hyperdivergent Skeletal Class II Malocclusion with Steep Posterior Occlusal Plane in a Camouflage Case.

Severe hyperdivergent skeletal Class II malocclusion may be ideally treated with orthognathic surgery in adult patients. Here, we report a camouflage treatment of a 23-year-old female patient. She was diagnosed with a skeletal Class II malocclusion with extreme high mandibular plane angle, retrusive mandible, steep posterior occlusal plane, anterior open bite, and severe overjet. The treatment plan included extraction of all second premolars and intrusion of the maxillary anterior teeth and mandibular posterior teeth using miniscrews. These contributed to an effective counterclockwise rotation of the mandible, decreased lower face height, and improvement in anterior overbite. This case report shows a vertical control strategy on severe hyperdivergent skeletal Class II malocclusions, which achieves well-controlled sagittal and vertical dimensions and a favorable facial appearance. The treatment and retention results were well balanced and aesthetically pleasing.

[Clinical details in the diagnosis of Kawasaki disease]. / å·å´Žç— è¯Šæ–­è¿‡ç¨‹ä¸­éœ€è¦æ³¨æ„çš„ä¸´åºŠç»†èŠ‚.

Kawasaki disease (KD) is one of the leading causes of acquired heart diseases in children aged under 5 years. The clinical manifestations of KD include fever, changes in the extremities, rash or redness at the site of bacille Calmette-Guérin vaccination, bilateral bulbar conjunctival hyperemia, changes in lips and mouth, nonsuppurative cervical lymphadenopathy, and other systemic manifestations. There are difficulties in the diagnosis of KD due to its asynchronous clinical manifestations. With reference to the latest case reports and research advances in KD, this article summarizes the clinical details in the diagnosis of KD, so as to improve the level of clinical diagnosis of KD.

AIE Nanoassemblies for Discrimination of Glycosaminoglycans and Heparin Quality Control.

The discrimination of glycosaminoglycans (GAGs) is a challenging task but of great importance to ensure their safe use in clinics. Herein, four supramolecular AIE nanoassemblies denoted as PDDA-TPE100, PDDA-TPE75, PDDA-TPE50, and PDDA-TPE25 were synthesized by loading different amounts of the negatively charged AIEgen TPE onto the surface of the positively charged polymer PDDA. These AIE nanoassemblies were utilized for the construction of a fluorescent sensor array, which was able to discriminate various GAGs on the basis of a compaction to displacement reaction mechanism. LDA and HCA results revealed that GAGs including Hep, Chs, HA, CTS, DS, and OSCS can be discriminated with 100% accuracy. The four-sensor array was then simplified to a three-sensor array using PDDA-TPE100, PDDA-TPE75, and PDDA-TPE50 as the sensors, which was determined to be still powerful in discrimination of various GAGs, accurate identification of unknown GAG samples, sensitive detection of trace OSCS contaminant in Hep, and identification of Hep and other biologically abundant anions. Moreover, the three-sensor array was even successfully applied for differentiating GAGs in serum media.

Investigating the repair of alveolar bone defects by gelatin methacrylate hydrogels-encapsulated human periodontal ligament stem cells.

Although various efforts have been made to develop effective treatments for alveolar bone defect, alveolar regeneration has been emerging as the one with the most potential Herein, we investigated the potential of gelatin methacrylate (GelMA) hydrogels-encapsulated human periodontal ligament stem cells (hPDLSCs) to regenerate alveolar bone. The easy, rapid, and cost-effective nature of GelMA hydrogels makes them a promising mode of stem cell-delivery for clinically relevant alveolar bone regeneration. More importantly, GelMA hydrogels provide an optimal niche for hPDLSCs proliferation, migration and osteogenic differentiation, which are critical for alveolar bone regeneration. In this study, we examined the microstructure of GelMA hydrogels, and identified a highly porous and interconnected network. Compressive test of GelMA hydrogels showed that the stress reached a maximum value of 13.67 ± 0.03 kPa when the strain reached 55%. The maximum values of swelling ratio were 700 ± 47% at the fifth hour. The proliferation rate of hPDLSCs in the GelMA hydrogels resembled that in 2D culture and gradually increased. We established a critical-sized rat model of alveolar bone defects, and applied Micro-CT to assess new bone formation. Compared to the control group, there was substantial bone regeneration in the GelMA + hPDLSCs group at both 4 and 8 weeks after the operation. Histological analysis results were consistent with Micro-CT results. Our study demonstrates that the GelMA hydrogels-encapsulated hPDLSCs have a significant alveolar regenerative potential, and may represent a new strategy for the therapy of alveolar bone defects.

Genome-wide association study reveals multiple loci associated with primary tooth development during infancy.

Tooth development is a highly heritable process which relates to other growth and developmental processes, and which interacts with the development of the entire craniofacial complex. Abnormalities of tooth development are common, with tooth agenesis being the most common developmental anomaly in humans. We performed a genome-wide association study of time to first tooth eruption and number of teeth at one year in 4,564 individuals from the 1966 Northern Finland Birth Cohort (NFBC1966) and 1,518 individuals from the Avon Longitudinal Study of Parents and Children (ALSPAC). We identified 5 loci at P<5x10(-8), and 5 with suggestive association (P<5x10(-6)). The loci included several genes with links to tooth and other organ development (KCNJ2, EDA, HOXB2, RAD51L1, IGF2BP1, HMGA2, MSRB3). Genes at four of the identified loci are implicated in the development of cancer. A variant within the HOXB gene cluster associated with occlusion defects requiring orthodontic treatment by age 31 years.

Self-Cross-Linkable Maleic Anhydride Terpolymer Coating with Inherent High Antimicrobial Activity and Low Cytotoxicity.

Developing coating materials with low cytotoxicity and high antimicrobial activity has been recognized as an effective way to prevent medical device-associated infections. In this study, a maleic anhydride terpolymer (PPTM) is synthesized and covalently attached to silicone rubber (SR) surface. The formed coating can be further cross-linked (SPM) through the self-condensation of pendent siloxane groups of terpolymer. No crack or delamination of SPM was observed after 500 cycles of bending and 7 day immersion in deionized water. The sliding friction force of a catheter was reduced by 50% after coating with SPM. The SPM coating without adding any extra antibacterial reagents can kill 99.99% of Staphylococcus aureus and Escherichia coli and also significantly reduce bacterial coverage, while the coating displayed no antimicrobial activity when maleic anhydride groups of SPM were aminated or hydrolyzed. The results of the repeated disinfection tests showed that the SR coated with SPM could maintain 87.3% bactericidal activity within 5 cycles. Furthermore, the SPM coating only imparted slight toxic effect (>85% viability) on L929 cells after 36 h of coculture, which is superior to the coating of aminated SPM conjugated with the antimicrobial peptide E6. The terpolymer containing maleic anhydride units have great potential as a flexible and durable coating against implant infections.

Ammonia fiber expansion-assisted deep eutectic solvent treatment for wheat straw fraction separation and bioconversion.

In this study, an ammonia fiber expansion (AFEX)-assisted deep eutectic solvent (DES) pretreatment method was developed for the rapid separation of wheat straw fractions, which reduced the pretreatment time for DES and improved the pretreatment efficiency. This study describes the feasibility of the AFEX-assisted DES pretreatment in terms of both progressive and parallel relationships and analyzes the subsequent enzymatic effect in generating glucose from cellulose. Ammonia fiber expansion-assisted DES one-pot pretreatment at 120 °C, for 1.5 h resulted in an enzymatic efficiency of 98.0 ± 3.1 %. Moreover, the enzyme efficiency remained greater than 85 % after three recovery cycle experiments. The comparison between regenerated-lignin (d-lignin) and alkaline-lignin showed that regenerated lignin has a lower molecular weight and belongs to para-hydroxy-phenyl-guaiacyl-syringyl (H-G-S) type lignin. This study developed is a green and efficient pretreatment process with great potential in the separation and utilization of biomass fractions.

Efficacy of a modified twin block appliance compared with the traditional twin block appliance in children with hyperdivergent mandibular retrognathia: protocol for a single-centre, single-blind, randomised controlled trial.

INTRODUCTION: Compensatory mouth breathing, caused by nasopharyngeal obstructive diseases, is the main cause of hyperdivergent mandibular retrognathia in children. Such deformities require effective growth guidance before pubertal growth peaks. The traditional mandibular advancement device, twin block (TB), can guide the forward development of the mandible. However, the side effect of increasing the vertical dimension of the lower facial third, worsens the facial profile of children with divergent growth trends. To solve this problem, a modified TB (LLTB) appliance was designed to control the vertical dimension by intruding incisors and inhibiting the elongation of posterior teeth during the advancement of the mandible, which could avoid the side effects of traditional appliances and effectively guide the growth of the mandible in a normal direction. METHODS AND ANALYSIS: The study was designed as a single-centre, single-blind, randomised, parallel controlled trial. We aim to enrol 60 children aged 9-14 years with hyperdivergent skeletal class II malocclusion, using a 1:1 allocation ratio. The participants were will be randomly assigned to receive either the TB or LLTB treatment. The primary outcome will be a change in the angle of the mandibular plane relative to the anterior cranial base. The secondary outcomes will include changes in the sagittal maxillomandibular relation, occlusal plane, facial height, morphology of the mandible and upper airway width. Safety endpoints will also be evaluated. ETHICS AND DISSEMINATION: Ethical approval was obtained from the ethics committee of Shanghai Stomatological Hospital. Both participants and their guardians will be fully informed of the study and sign an informed consent form before participating in the trial. The results will be publicly available in peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: ChiCTR2000035882.

Porous fibrous bacterial cellulose/La(OH)3 membrane for superior phosphate removal from water.

Lanthanum (La)-based nanoparticles (NPs) are promising candidates for phosphate removal owing to their inherently high affinity towards phosphate. However, significant challenges remain to be addressed before their practical deployment, especially the problems associated with their aggregation. Herein, we fabricated a high-efficient sorbent for phosphate removal through in-situ synthesizing La(OH)3 NPs on a natural support, bacterial cellulose (BC), which is pre-modified with polyethyleneimine. The resultant La(OH)3 NPs-immobilized BC with different La contents (BPLa-X) exhibited a highly fibrous porous structure, in which BPLa-3 was selected for further phosphate adsorption studies. BPLa-3 demonstrated a high adsorption capacity of 125.5 mg P g-1, and high adsorption selectivity due to the large surface area and abundant exposed active adsorption sites for phosphate. Additionally, BPLa-3 also displayed high reusability and still possessed high adsorption capacity after four consecutive cycles of adsorption-desorption. Therefore, the present adsorbent is believed to be a promising candidate for practical phosphate removal.

DESIGN, CONSTRUCTION AND TEST OF GAMMA IONIZATION CHAMBERS.

Ionization chamber is considered as the golden standard for the dosemeter. This work fabricated one graphite-walled and two polymethyl methacrylate (PMMA)-walled ionization chambers, tested respectively and compared their characteristic parameters. The performance of graphite-walled chamber was similar to that of the PMMA-walled chamber. The relative energy response of ionization chambers was lower than 4% from 50 keV to 50 MeV based on the FLUKA code simulation results. The experimental data showed that the ionization chambers performed well in linearity and repeatability. Assuming the chambers sensitive volume and HV bias was constant, the measured maximum saturation absorbed dose of ionization chambers changed with the diameter variation of chambers anode based on the comparison results of two PMMA-walled ionization chambers.

Encapsulating Amidoximated Nanofibrous Aerogels within Wood Cell Tracheids for Efficient Cascading Adsorption of Uranium Ions.

Continuous filtering adsorption has drawn growing interest in the exploration of uranium resources in seawater and reduction in the environmental risks of uraniferous wastewater from nuclear industries. For most filtering adsorbents, repeated filtration, high membrane thickness, and high pressure are normally essential to achieve both a high rejection ratio and high filtration flux. Herein cellulose fibrils were preferentially exfoliated from the lignin-poor layer of secondary cell walls of balsa wood during an in situ amidoximation process. By maintaining honeycomb-like cellular microstructures and cellulose aerogel stuffing in their cell tracheids, the resultant nanowoods showed superior mechanical properties (e.g., compressive strength ∼1.3 MPa in transverse direction) with large surface areas (∼80 m2 g-1). When their cell tracheids were aligned perpendicular to the flow and the edges sealed with a thermoset polymer, they could serve as efficient and high-pressure filtration membranes to capture aquatic uranium ions. In analogy to a typical cascading filtration system, the filtrate passed successively the layered-organized cell tracheids through abundant micropores on their cell walls, enabling a high rejection ratio of >99% and flux of ∼920 L m-2 h-1 under pressure up to 6 bar (membrane thickness of 2 mm). Thus, this study not only provides an in situ approach to producing robust woods with functional nanocellulose encapsulated into their cell tracheids but also offers a sustainable route for high-efficiency extraction of aqueous uranium.

[Preparation and characterization of niosomes of Semen Strychni alkaloids extract].

OBJECTIVE: To prepare a noisome formulation of Semen Strychni alkaloids extract with high encapsulation efficiency. METHOD: S. Strychni alkaloids were encapsulated into niosomes by pH gradient loading method. The factors influencing on the encapsulation efficiency were investigated, and formulation and preparation process of niosomes were optimised and validated. RESULT: When the drug to lipid weight ratio was under 1: 10, pH gradient in buffer solution of citric acid at 50 degrees C was more than 4.0, the niosomes (mean diameter 179.2 nm and Zeta potential -25.41 mV) were formed with encapsulation efficiency of over 86.9%. CONCLUSION: The pH gradient loading method was reliable for preparing niosomes of Semen Strychni alkaloids extract.

Peg-Enhanced Behavioral Recovery After Sciatic Nerve Transection and Either Suturing Or Sleeve Conduit Deployment in Rats.

Polyethylene glycol (PEG) has previously been reported to improve outcomes of peripheral nerve microsuturing. However, recent studies have challenged this finding. Given its clinical importance, we investigated the potential of PEG as a facilitator of peripheral nerve restoration. The sciatic nerve of 144 rats was transected and submitted either to simple suturing (Group A), PEG-enhanced suturing (Group B), and insertion in an arterial sleeve conduit without PEG (Group C), or with PEG (Group D) in equal numbers. Behavioral recovery was assessed with the sciatic function index (SFI). Nerve impulse conduction was assessed with compound muscle action potentials (CMAPs). Histology comprised standard hematoxylin/eosin staining, electron microscopy and glial cell line-derived neurotrophic factor (GDNF) immunohistochemistry. Expression of GDNF was also assessed with western blotting. Results were evaluated at weeks 1, 4, and 8. PEG treatment significantly improved behavioral recovery and morphology of nerve restoration, particularly in the sleeve conduit group, relative to that of controls. In conclusion, PEG may improve outcomes of peripheral nerve reconstruction.

Simethicone administration improves gastric cleanness for esophagogastroduodenoscopy: a randomized clinical trial.

BACKGROUND: Esophagogastroduodenoscopy is very useful in diagnosing and treating upper gastrointestinal mucosal disorders, but too much foam and water in stomach decrease its diagnostic efficiency. Simethicone administration can help remove excessive foam. AIMS: To determine the optimal simethicone administration strategies in a comparative randomized controlled clinical trial. METHODS: Adult outpatients with indications for esophagogastroduodenoscopy were enrolled and randomly divided into group 1 (simethicone solution intake 20-30 min before procedure, n = 110), group 2 (simethicone solution intake 31-60 min before procedure, n = 92), and group 3 (simethicone solution intake > 60 min before procedure). Primary and secondary outcomes were procedure time and the patients' satisfaction after the examination. All symptoms like abdominal pain and distension were recorded. RESULTS: No statistically significant differences were found on the patients' demographic and clinical features and mean examination time (all P values > 0.05). The distribution of patients with different endoscopic and pathological diagnosis was comparable among three groups, respectively (P = 0.607; P = 0.289). However, the proportion of patients with Gastric Cleanness Grade A was most in group 2 (n = 73, 79.3%), and patient proportion with Gastric Cleanness Grade C was most found in group 1 (n = 72, 65.5%), which was greatly different (P < 0.001). There was no statistically significant difference on the satisfaction scores [immediately 6 (3-8) vs. 6 (1-10) vs. 6 (1-9), P = 0.533; 2 h after 10 (8-10) vs. 10 (10-10) vs. 10 (8-10), P = 0.463]. CONCLUSION: Simethicone solution intake 31-60 min before esophagogastroduodenoscopy can help obtain the best gastric cleanness, which is recommended in clinical practice (registered at ClinicalTrials.gov, NCT03776916 on December 13, 2018).

Hyper-IgE syndrome with STAT3 mutation: a case report in Mainland China.

Hyper-immunoglobulin E syndromes (HIES) including compound primary immunodeficiency and nonimmunological abnormalities are characterized by extremely high serum IgE levels, eosinophilia, eczema, susceptibility to infections, distinctive facial appearance, retention of deciduous teeth, cyst-forming pneumonias, and skeletal abnormalities. Itis reported that some cases of familial HIES are relative to autosomal dominant or recessive inheritance, but most cases are sporadic, and result from mutations in the human signal transducer and activator of transcription 3 (STAT3) gene. In this paper, we firstly report a young man diagnosed of Hyper-IgE syndrome with STAT3 mutation in Mainland China, and investigate the autosomal dominant trait of his family members.

[Human dental pulp stem cells conditioned medium protects genioglossus myoblast from cobalt chloride-induced hypoxia injury through AMPK/PGC-1α pathway].

PURPOSE: To study the effect of hypoxia induced by cobalt chloride (CoCl2) on viability and oxidative stress of genioglossus myoblast, and to explore the mechanism of the protective effect of conditioned medium (CM) on human dental pulp stem cells (hDPSCs). METHODS: The hDPSCs were isolated and cultured, and the conditioned medium was prepared by ultrafiltration concentration. Mouse genioglossus myoblasts were isolated and divided into control group, CM group, CoCl2 group and CoCl2+CM group. The cell viability of genioglossus myoblasts was detected by CCK-8. The intracellular and mitochondrial ROS levels were evaluated by DCFH-DA and MitoSOX, respectively. The expression level of mitochondria-related genes in NRF-1 and NRF-2 were analyzed by real-time PCR. The expression of PGC-1α, p-AMPK and total AMPK protein was detected by Western blot. Statistical analysis was performed using SPSS 22.0 software package. RESULTS: The proliferation of genioglossus myoblasts was significantly decreased after 200 µmol/L CoCl2 treatment for 24 h (P<0.05), and the levels of reactive oxygen species (ROS) were significantly increased in intracellular and mitochondria (P<0.05). Compared with CoCl2 group, the proliferation ability of hDPSCs-CM was dramatically raised (P<0.05), and the intracellular and mitochondrial ROS content was remarkably decreased(P<0.05). hDPSCs-CM up-regulated the protein expression levels of pAMPK and PGC-1α in genioglossus myoblasts and mitochondrial downstream effectors of PGC-1α, including mRNA expression levels of NRF-1, NRF-2 (P<0.05). CONCLUSIONS: Human dental pulp stem cells conditioned medium can alleviate hypoxia injury induced by CoCl2 in genioglossus myoblasts, and its mechanism may be related to AMPK/PGC-1α signaling pathway.

The secretome of human dental pulp stem cells protects myoblasts from hypoxia­induced injury via the Wnt/ß­catenin pathway.

Human dental pulp stem cells (hDPSCs) present several advantages, including their ability to be non­invasively harvested without ethical concern. The secretome of hDPSCs can promote the functional recovery of various tissue injuries. However, the protective effects on hypoxia­induced skeletal muscle injury remain to be explored. The present study demonstrated that C2C12 myoblast coculture with hDPSCs attenuated CoCl2­induced hypoxic injury compared with C2C12 alone. The hDPSC secretome increased cell viability and differentiation and decreased G2/M cell cycle arrest under hypoxic conditions. These results were further verified using hDPSC­conditioned medium (hDPSC­CM). The present data revealed that the protective effects of hDPSC­CM depend on the concentration ratio of the CM. In terms of the underlying molecular mechanism, hDPSC­CM activated the Wnt/ß­catenin pathway, which increased the protein levels of Wnt1, phosphorylated­glycogen synthase kinase­3ß and ß­catenin and the mRNA levels of Wnt target genes. By contrast, an inhibitor (XAV939) of Wnt/ß­catenin diminished the protective effects of hDPSC­CM. Taken together, the findings of the present study demonstrated that the hDPSC secretome alleviated the hypoxia­induced myoblast injury potentially through regulating the Wnt/ß­catenin pathway. These findings may provide new insight into a therapeutic alternative using the hDPSC secretome in skeletal muscle hypoxia­related diseases.

PDGFBB-modified stem cells from apical papilla and thermosensitive hydrogel scaffolds induced bone regeneration.

Bone defects caused by cancer surgery or trauma have a strong negative impact on human health. Treatment with cell and material-based complexes provides an alternative strategy for the regeneration of damaged bone tissue. The good physical properties and suitable biodegradability of a thermosensitive hydrogel has been shown to act as a valuable scaffold. Platelet derived growth factor BB (PDGFBB) is mainly secreted by platelets and promotes the migration and angiogenesis of mesenchymal stem cells (MSCs). Although PDGFBB is known to indirectly enhance bone repair in vivo, the effects of PDGFBB on stem cells from apical papilla (SCAPs) require further investigation. In our study, the proliferation of cells was investigated by the cell counting kit-8 and live/dead staining methods. The results indicated that PDGFBB promoted the proliferation of SCAPs. Real-time polymerase chain reaction and Western blot experiments were used to detect osteogenic genes and proteins. Moreover, calvarial defects were created in Sprague-Dawley rats and different complexes implanted. The results shown by micro-CT and hematoxylin and eosin analysis demonstrated that the hydrogel combined with lentiviral supernatant-green fluorescent protein-PDGFBB significantly improved new bone formation and mineralization compared with the other three groups. In summary, our research showed that a thermosensitive hydrogel can be used as a scaffold for 3D cell culture, and PDGFBB gene-modified SCAPs can improve bone formation in calvarial defects.

Measurement of stable and radioactive cesium in natural waters by the diffusive gradients in thin films technique with new selective binding phases.

A cesium-specific diffusive gradients in thin films (DGT) technique was developed using copper ferrocyanide (CFCN) as the binding agent. Two types of DGT binding phases were evaluated, one by immobilizing CFCN on Chelex 100 resin gels (Chelex-CFCN) and the other on poly(acrylic acid) gels (PAA-CFCN). Both DGT devices were successfully applied to the measurement of low levels of stable 133Cs and radioactive 137Cs in synthetic solutions and in natural river waters. In all cases, the DGT labile concentrations measured with the PAA-CFCN DGT agreed very well with total dissolved Cs concentrations, whereas those measured by the Chelex-CFCN DGT were much lower than total Cs concentrations. The difference was attributed to the different binding kinetics of Cs+ on the two gels suggesting that this might be a promising means of measuring biologically relevant Cs concentrations in natural waters.