A structural equation modeling approach to determine the correlation between the vertical and sagittal skeletal patterns and posterior basal bones mismatching in patients with skeletal Class III malocclusion.

INTRODUCTION: Matching the maxillomandibular basal bone width is essential to the stability of orthodontic treatment. We aimed to determine the relationship between basal bone width mismatching and the vertical and sagittal skeletal pattern in patients with skeletal Class III malocclusion through shape analysis and structural equation modeling (SEM). METHODS: Cone-beam computed tomography images were collected from 45 men and 51 women. Width mismatching of the basal bone was determined using generalized Procrustes analysis. Twenty-two parameters from the synthesized cephalogram were measured, followed by factor analysis and SEM. RESULTS: Mismatch occurred at the second molar (men, -4.29 ± 4.32 mm; women, -5.55 ± 4.43 mm) and retromolar regions (men, -8.49 ± 5.11 mm; women: -8.93 ± 5.25 mm). The sum of angles had the largest loading for vertical-1 (extracted from 18 vertical cephalometric measurements) (men, 0.9477; women, 0.9489), followed by MP-SN angle (0.9408) in men and N-Me/S-Go (0.9342) in women. Wits appraisal and anteroposterior dysplasia indicator were largest for Sagittal-1. SEM showed a positive effect of male vertical-1 and 2 on width difference in the retromolar region (P <0.001; B >0). Female vertical-1 had a significant positive effect on DW7 (P <0.001; B = 5.535) and DWR (P = 0.016; B = 3.427) as vertical-2. Sagittal-1 showed a negative correlation with DW7 in both genders (P <0.05; B <0) and with DWR in men. CONCLUSIONS: Basal bone width mismatching occurred at the second molar and retromolar regions, especially in low-angle and patients with severe skeletal Class III malocclusion.

Radiotherapy vs sequential pegaspargase, gemcitabine, cisplatin and dexamethasone and radiotherapy in newly diagnosed early natural killer/T-cell lymphoma: A randomized, controlled, open-label, multicenter study.

To compare the efficacy and safety of radiotherapy (RT) and chemotherapy of pegaspargase, gemcitabine, cisplatin and dexamethasone (DDGP) combined with RT in newly diagnosed stage I-II natural killer/T-cell lymphoma (NKTL), we designed a randomized, controlled, open-label, multicenter clinical trial. Data from 65 stage I-II NKTL patients whose diagnoses were confirmed using immunohistochemistry were enrolled from January 2011 to December 2013 in the First Affiliated Hospital of Zhengzhou University. Patients were randomly divided into the RT group (n = 35) and the DDGP combined with RT group (n = 30). There was a difference between the Eastern Cooperative Oncology Group (ECOG) score in the two arms (P = .013). The complete response rate (CRR) and objective response rate (ORR) of DDGP combined with RT group were superior to those in the RT group (CRR: 73.3% vs 48.6%; ORR: 83.3% vs 60.0%, respectively). The 5-year progression-free survival (PFS) rate and overall survival (OS) rate in the DDGP combined with RT group were higher than those in the RT group (82.9% vs 56.5% for PFS, P = .023; 85.7% vs 60.4% for OS, P = .040), and treatment methods and lactate dehydrogenase were independent risk factors. Myelosuppression (P < .001), gastrointestinal reactions (P < .001), abnormal liver function (P = .007), coagulation abnormalities (P < .001) and baldness (P < .001) were more likely to occur in the DDGP combined with RT group. In conclusion, DDGP combined with radiotherapy obviously obtained great efficacy and prolonged the survival time of patients, also the side effects were mild for stage I-II NKTL. This trial was registered at https://register.clinicaltrials.gov as #NCT01501136.

Sustained zinc release in cooperation with CaP scaffold promoted bone regeneration via directing stem cell fate and triggering a pro-healing immune stimuli.

Metal ions have been identified as important bone metabolism regulators and widely used in the field of bone tissue engineering, however their exact role during bone regeneration remains unclear. Herein, the aim of study was to comprehensively explore the interactions between osteoinductive and osteo-immunomodulatory properties of these metal ions. In particular, the osteoinductive role of zinc ions (Zn2+), as well as its interactions with local immune microenvironment during bone healing process, was investigated in this study using a sustained Zn2+ delivery system incorporating Zn2+ into ß-tricalcium phosphate/poly(L-lactic acid) (TCP/PLLA) scaffolds. The presence of Zn2+ largely enhanced osteogenic differentiation of periosteum-derived progenitor cells (PDPCs), which was coincident with increased transition from M1 to M2 macrophages (M[Formula: see text]s). We further confirmed that induction of M2 polarization by Zn2+ was realized via PI3K/Akt/mTOR pathway, whereas marker molecules on this pathway were strictly regulated by the addition of Zn2+. Synergically, this favorable immunomodulatory effect of Zn2+ further improved the osteogenic differentiation of PDPCs induced by Zn2+ in vitro. Consistently, the spontaneous osteogenesis and pro-healing osteoimmunomodulation of the scaffolds were thoroughly identified in vivo using a rat air pouch model and a calvarial critical-size defect model. Taken together, Zn2+-releasing bioactive ceramics could be ideal scaffolds in bone tissue engineering due to their reciprocal interactions between osteoinductive and immunomodulatory characteristics. Clarification of this synergic role of Zn2+ during osteogenesis could pave the way to develop more sophisticated metal-ion based orthopedic therapeutic strategies.

Effectiveness of gemcitabine, pegaspargase, cisplatin, and dexamethasone (DDGP) combination chemotherapy in the treatment of relapsed/refractory extranodal NK/T cell lymphoma: a retrospective study of 17 patients.

The prognosis of extranodal nature killer (NK)/T cell lymphoma (ENKL) is dismal because of its aggressive course and multidrug resistance. Currently, for patients with relapsed/refractory ENKL, L-asparaginase-based regimens such as L-asparaginase, ifosfamide, methotrexate, etoposide, and dexamethasone (SMILE) or L-asparaginase, methotrexate, and dexamethasone (AspaMetDex) are recommended. We retrospectively investigated the efficacy and safety of gemcitabine, pegaspargase, cisplatin, and dexamethasone (DDGP) combination chemotherapy in the treatment of 17 relapsed/refractory ENKL patients. Clinical data from these patients were collected and analyzed. The primary end point was overall response rate (ORR). All patients were subjected to 2 to 6 cycles of DDGP chemotherapy, and the median number of cycles of DDGP regimen administrated was four. The ORR was 88.2 % (15/17), with nine patients (52.9 %) achieved complete response (CR) and six patients (35.3 %) achieved partial response (PR). The median follow-up time was 17 months (range 2-28 months). The 1-year overall survival (OS) rate and 1-year progression-free survival (PFS) were 82.4 and 64.7 %, respectively. For those CR responders, the median PFS was 17 months. Grade 3/4 neutropenia occurred in nine patients (52.9 %) and grade 3/4 thrombocytopenia occurred in six patients (35.3 %). DDGP combination chemotherapy produces favorable outcomes in relapsed/refractory ENKL, and more attention should be paid to treatment-related myelosuppression. Further prospective trials are expected to define the efficacy.

Polarized P(VDF-TrFE) film promotes skin wound healing through controllable surface potential.

Surface potential of biomaterials is found to be important for wound healing. Here, poly(vinylidenefluoride-co-trifluoroethylene) (P(VDF-TrFE)) films with different surface potentials and piezoelectric responses were prepared and explored for the effect of surface potential on wound healing. The crystalline state of P(VDF-TrFE) films were characterized with X-ray diffraction (XRD), differential scanning calorimetry (DSC) and Fourier-transformed infrared spectroscopy (FTIR), illustrated that the electric polarization will promote the crystallization of the ß phase of P(VDF-TrFE), in which the content of ß phase increased from 82.9 % to 86.8 % compared with the control. Then, Kelvin potential and piezoelectric coefficient d33 were to evaluate surface potential and polarization performance. Moreover, bovine serum albumin (BSA) adsorption and cell culture results showed that high surface potential can promote protein adsorption as well as fibroblast proliferation and macrophage polarization. Finally, in vivo experiments indicated that high voltage polarized P(VDF-TrFE) films can generate higher dynamic potential up to 2.3 V, and promoted wound healing from the phases of inflammation, proliferation and remodeling, the wound healing rate of which was 88.8 % ± 0.8 %, significantly higher than 79.1 % ± 2.5 % and 86.4 % ± 1.8 % of blank and control. In general, this work revealed that polarized P(VDF-TrFE) films can promote wound healing, shed light on designing wound healing materials with similar properties.

Regulation of Macrophage Polarization on Chiral Potential Distribution of CFO/P(VDF-TrFE) Films.

Surface potentials of biomaterials have been shown to regulate cell fate commitment. However, the effects of chirality-patterned potential distribution on macrophage polarization are still only beginning to be explored. In this work, we demonstrated that the chirality-patterned potential distribution of CoFe2O4/poly(vinylidene fluoride-trifluoroethylene) (CFO/P(VDF-TrFE)) films could significantly down-regulate the M1 polarization of bone marrow-derived macrophages (BMDMs). Specifically, the dextral-patterned surface potential distribution simultaneously up-regulated the expression of M2-related markers of BMDMs. The results were attributed to the sensitive difference of integrin subunits (α5ß1 and αvß3) to the dextral- and sinistral-patterned surface potential distribution, respectively. The interaction difference between the integrin subunits and surface potential distribution altered the cell adhesion and cytoskeletal structure and thereby the polarization behavior of BMDMs. This work, therefore, emphasizes the importance of chirality of potential distribution on cell behavior and provides a new strategy to regulate the immune response of biomaterials.

Regulating mechanical performance of poly (l-lactide acid) stent by the combined effects of heat and aqueous media.

Annealing process has been applied to the development of thermoforming polymer braided stent and treating its basic constitute monofilaments, especially for Poly (l-lactide acid) (PLLA) condensed by lactic acid monomer made from the plant starch. In this work, high performance monofilaments were produced by melting spun and solid-state drawing methods. Inspired by the effects of water plasticization on semi-crystal polymer, PLLA monofilaments were annealed with and without constraint in vacuum and aqueous media. Then, the co-effects of water infestation and heat on the micro-structure and mechanical properties of these filaments were characterized. Furtherly, mechanical performance of PLLA braided stents shaped by different annealing methods was also compared. Results showed that annealing in aqueous media generated more obvious structure change of PLLA filaments. Interestingly, the combined effects of aqueous phase and thermal effectively increased the crystallinity, and decreased the molecular weight and orientation of PLLA filaments. Therefore, higher modulus, smaller strength, and elongation at the break for filaments could be obtained, which could furtherly realize better radial compression resistance of the braided stent. This annealing strategy could provide new perspectives between anneal and material properties of PLLA monofilaments, and provide more suitable manufacturing technics for polymer braided stent.

The osteogenic response to chirality-patterned surface potential distribution of CFO/P(VDF-TrFE) membranes.

Piezoelectric poly(vinylidene fluoride-trifluoroethylene) has demonstrated an ability to promote osteogenesis, and biomaterials with a chirality-patterned topological surface could enhance cellular osteogenic differentiation. In this work, we created a chirality-patterned surface potential distribution of CoFe2O4/poly(vinylidene fluoride-trifluoroethylene (CFO/P(VDF-TrFE)) membranes to explore their osteogenic response under no change in surface chemical and topology, attempting to further strengthen the ability of the membranes to promote osteogenesis. The chirality-patterned surface potential distribution was established by microdomain contact polarization with the help of sinistral/dextral-patterned ITO interdigital microelectrodes. In the in vitro evaluations, the mesenchymal stem cells showed a positive response in osteogenic differentiation to CFO/P(VDF-TrFE) membranes with both sinistral- and dextral-patterned surface potential distributions, however, the dextral-patterned distribution gave a stronger response than the sinistral-patterned one. And the in vivo evaluation showed a response tend in new bone tissue formation similar to the in vitro evaluations. The stronger response in osteogenic differentiation and osteogenesis for the CFO/P(VDF-TrFE) membrane with the dextral-patterned distributions may be attributed to that the intense interaction of the cells with the electrophysiological microenvironment appears due to a correspondingly higher expression of integrin α5ß1, which significantly up-regulates the Arp2/3 complex expression, a crucial factor for cytoskeleton reorganization, possibly increases cytoskeleton contractility, and strengthens the transduction of the osteogenesis-related signaling cascade. This work proves that the chirality-patterns in surface potential distributions could provide an osteogenic response similar to a chirality-patterned topological surface.

Supramolecular Self-Assembly of Herbicides with Reduced Risks to the Environment.

The side effects caused by some pesticides with high off-target movement have brought great risks to the environment and human health. Here, taking 2,4-dichlorophenoxyacetic acid (2,4-D) as a model herbicide to reduce its volatilization and leaching, a supramolecular self-assembly mediated by branched polyethylenimine (B-PEI) was constructed through noncovalent molecular recognition. The results showed that 2,4-D/B-PEI nanoparticles (NPs) with a mean particle size of 168 nm can be formed by electrostatic interaction, hydrophobic effect, and π-π stacking when the mass ratio of 2,4-D to B-PEI with the average molecular weight of 10 000 (B-PEI 10k) was 40:20, and their generation was not susceptible to common inorganic ions such as Ca2+, Na+, Cl-, and SO42-. Compared with 2,4-D, the self-assembled NPs with improved physicochemical properties including strong positive charges (+58.2 mV), reduced volatilization rate (2.50%), low surface tension (56.10 mN m-1), and decreased leaching potential could minimize the adverse impacts of this herbicide on the environment. The biological activity experiments in the greenhouse and field demonstrated that the control efficacy of NPs without using any surfactant against weeds was almost the same as that of the 2,4-D sodium salt form containing Tween 80. The safety tests showed that the self-assembled NPs had the same genotoxicity as 2,4-D to Vicia faba and little effect on the soil enzyme activities. Overall, the development of self-assembled herbicidal nanoformulations with desirable physicochemical properties and low risks to the environment would have potential application in agricultural production.

Functionalized Silver Nanocapsules with Improved Antibacterial Activity Using Silica Shells Modified with Quaternary Ammonium Polyethyleneimine as a Bacterial Cell-Targeting Agent.

Silver nanoparticles (AgNPs) have remarkable and broad-spectrum antibacterial activities against Gram-positive (G+) and Gram-negative bacteria (G-). However, the negative surface potential of AgNPs limits their antibacterial activities due to the electrostatic repulsion with the negatively charged bacterial cell membrane. To address the limitation, AgNPs were loaded in the mesoporous silica nanoparticles by preparing silver core-mesoporous silica shell nanocapsules (Ag@MSNs), and then, a cationic antibacterial polymer, quaternary ammonium polyethyleneimine (QPEI), was used to modify Ag@MSNs for improving their surface potential and antibacterial activities. The results showed that the obtained Ag@MSN-QPEI exhibited a high positive surface potential (+39.6 mV) and a strong electrostatic attraction with Pseudomonas syringae pv. lachrymans cells in coculture, resulting in an excellent bacterial cell-targeting effect. At the same concentration, Ag@MSN-QPEI exhibited less silver content (reducing the silver content of Ag@MSNs by 19%), higher antibacterial activities, and longer effective duration against Clavibacter michiganensis subsp. michiganensis (G+) and P. syringae pv. lachrymans (G-) than Ag@MSNs and QPEI alone. The excellent bacterial cell-targeting effect and synergistic antibacterial action combined with QPEI accounted for the significantly enhanced antibacterial activities of Ag@MSN-QPEI. Therefore, using a cationic antibacterial polymer to confer the bacterial cell-targeting effect and synergistic antibacterial action would be extended to other antimicrobial materials.

S100A9 and ORM1 serve as predictors of therapeutic response and prognostic factors in advanced extranodal NK/T cell lymphoma patients treated with pegaspargase/gemcitabine.

Pegaspargase combined with gemcitabine have greatly improved the outcomes of advanced extranodal NK/T cell lymphoma (ENKL). However, patients frequently undergo recurrent disease due to chemoresistance, and few predictive parameters are available. The present study explored potential biomarkers to predict the therapeutic response of advanced ENKL treated with pegaspargase/gemcitabine and evaluate the prognostic significance. Through serum proteomic analysis, we identified 61 upregulated and 22 downregulated proteins in nonresponders compared with responders. We further validated that patients with unfavourable treatment outcomes displayed higher levels of S100A9 and ORM1 via enzyme-linked immunosorbent assay (ELISA). Moreover, the sensitivity and specificity for detecting refractory patients were 81.5% and 71.4% for S100A9 > 62 ng/ml, 85.2% and 77.1% for ORM1 > 1436 ug/ml, 100% and 57.1% for S100A9 combined with ORM1. Furthermore, in multivariate analysis elevated levels of S100A9 were associated with poor 2-year OS (40.2% vs. 76.6%, RR = 2.92, p = 0.005) and 2-year PFS (33.1% vs. 61.1%, RR = 2.61 p = 0.011). High ORM1 also predicted inferior 2-year OS (38.7% vs.76.1, RR = 2.46, p = 0.023) and 2-year PFS (18.4% vs. 73.2%, RR = 2.86, p = 0.009). Our results indicated that S100A9 and ORM1 could serve as reliable predictors of therapeutic response and independent prognostic factors of survival in advanced ENKL patients treated with pegaspargase/gemcitabine.

Comparison of two porcine-derived materials for repairing abdominal wall defects in rats.

OBJECTIVE: The purpose of this study was to compare the mechanical properties, host responses and incorporation of porcine small intestine submucosa (PSIS) and porcine acellular dermal matrix (PADM) in a rat model of abdominal wall defect repair. MATERIALS AND METHODS: Prior to implantation, PSIS and PADM were prepared and evaluated in terms of structure and mechanical properties. Full-thickness abdominal wall defects were created in 50 Sprague-Dawley rats, and were repaired using either PSIS or PADM. Rats were sacrificed 1, 2, 4, 8 and 12 weeks post-repair and examined for herniation, infection, adhesions, contraction, and changes in the thickness and strength of the tissues incorporated at the defect sites. Histopathology and immunohistochemistry were performed to analyze inflammatory responses, collagen deposition and vascularization. RESULTS: PADM showed more dense collagen deposition and stronger mechanical properties than PSIS prior to implantation (P<0.01). However, the mechanical properties observed after integration with the surrounding native tissues was similar for PADM and PSIS. Both PADM and PSIS showed significant contraction by week 12. However, PADM tissue induced less adhesion and increased in thickness more slowly, and showed less infiltration by foreign giant cells, polymorphonuclear cells, and mononuclear cells. Improved remodeling of host tissue was observed after PSIS implantation, which was apparent from the orientation of bands of fibrous connective tissue, intermixed with newly formed blood vessels by Week 12. CONCLUSION: PSIS showed weaker mechanical properties prior to implantation. However, after implantation PSIS induced more pronounced host responses and showed better incorporation into host tissues than PADM.