Peroxisome proliferator-activated receptors as therapeutic target for cancer.

Peroxisome proliferator-activated receptors (PPARs) are transcription factors belonging to the nuclear receptor family. There are three subtypes of PPARs, including PPAR-α, PPAR-ß/δ and PPAR-γ. They are expressed in different tissues and act by regulating the expression of target genes in the form of binding to ligands. Various subtypes of PPAR have been shown to have significant roles in a wide range of biological processes including lipid metabolism, body energy homeostasis, cell proliferation and differentiation, bone formation, tissue repair and remodelling. Recent studies have found that PPARs are closely related to tumours. They are involved in cancer cell growth, angiogenesis and tumour immune response, and are essential components in tumour progression and metastasis. As such, they have become a target for cancer therapy research. In this review, we discussed the current state of knowledge on the involvement of PPARs in cancer, including their role in tumourigenesis, the impact of PPARs in tumour microenvironment and the potential of using PPARs combinational therapy to treat cancer by targeting essential signal pathways, or as adjuvants to boost the effects of current chemo and immunotherapies. Our review highlights the complexity of PPARs in cancer and the need for a better understanding of the mechanism in order to design effective cancer therapies.

The development of CD8 T-cell exhaustion heterogeneity and the therapeutic potentials in cancer.

CD8+ T cells are essential lymphocytes with cytotoxic properties for antitumor immunotherapy. However, during chronic infection or tumorigenesis, these cells often become dysfunctional with a gradually depleted ability to release cytokines and the exhibition of reduced cytotoxicity, the state referred to as "T-cell exhaustion" (Tex). This unique state was characterized by the increasing expression of inhibitory checkpoint receptors, and interventions targeting immune checkpoint blockades (ICBs) have been considered as a promising strategy to stimulate T-cell killing. Recent investigations have demonstrated that exhausted T cells not only display functional, metabolic, transcriptional, and epigenetic differences but also comprise a heterogeneous group of cells. In this review, we summarize the current findings on dynamic differentiation process during Tex heterogeneity development in cancer and chronic infection. We discuss how the responses to immunotherapy are determined by these distinct subsets and highlight prospective approaches for improving the efficacy of ICB therapy for cancer by leveraging the heterogeneity of T cells.

Immunotherapy of Epstein-Barr virus (EBV) infection and EBV-associated hematological diseases with gp350/CD89-targeted bispecific antibody.

Acute and persistent infection of Epstein-Barr virus (EBV) is associated with several life-threatening hematological disorders, including lymphoproliferative disorders (LPD), hemophagocytic lymphohistiocytosis (HLH), and chronic active Epstein-Barr virus infection (CAEBV). Currently, there are no efficacious virus-targeted therapies for EBV-driven hematological diseases. To explore the potential of phagocytosis-based immunotherapy, we created a bispecific antibody by targeting the viral envelope protein gp350 with a novel EBV-neutralizing antibody (named R1) that was paired with a monoclonal antibody against CD89 for redirecting macrophages and neutrophils. In vitro study showed that the bispecific antibody enabled efficient phagocytosis of EBV and killing of gp350 + lymphoma cells in the presence of PBMC. In vivo studies in NSG mice inoculated with EBV showed that bispecific antibody dramatically reduced the viral load in blood, solid organs and tissues. Treatment of mice implanted with EBV-harboring Raji lymphoma cells efficiently prevented tumor formation and massive metastasis to solid organs. Treatment of mice implanted with whole blood from EBV-HLH patients was effective in reducing viral levels in blood and solid organ. The gp350/CD89 bispecific antibody was highly effective in clearing EBV and immunotherapy of EBV-driven hematological diseases such as LPD and EBV-HLH.

MCP-1/CCR2 axis is involved in the regulation of γδT cells in lupus nephritis.

γδT cells are important innate immune cells that are involved in the occurrence and development of autoimmune diseases such as systemic lupus erythematosus (SLE). Lupus nephritis (LN) is a serious complication of SLE, characterized by the accumulation of immune cells (including γδT cells) in the target organs to participate in the disease process. Therefore, clarifying how γδT cells chemotactically migrate to target organs may be a key to developing therapeutic methods against LN. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of chemokines in LN patients and healthy controls. Real-time polymerase chain reaction (RT-PCR) and flow cytometry were used to measure the expression of chemokine receptors on the surface of γδT cells. The chemotactic migration ability of γδT cells was detected by Transwell assay. Signalling pathway activation of γδT cells was detected by Automated Capillary Electrophoresis Immunoassay and flow cytometry. The serum levels of chemokines, including monocyte chemoattractant protein-1 (MCP-1) in LN patients, were significantly increased. CCR2, the receptor of MCP-1, was also highly expressed on the surface of peripheral γδT cells in LN patients. In addition, the exogenous addition of MCP-1 can enhance chemotactic migration of γδT cells in LN patients. MCP-1 could activate STAT3 signalling in LN patients' peripheral γδT cells. γδT cells might participate in the pathogenesis of LN through MCP-1/CCR2 axis. This finding provides new opportunities for developing treatment methods against LN by targeting MCP-1/CCR2 axis.

An overview: Management of patients with advanced hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has constituted a significant health burden worldwide, and patients with advanced HCC, which is stage C as defined by the Barcelona Clinic Liver Cancer staging system, have a poor overall survival of 6-8 months. Studies have indicated the significant survival benefit of treatment based on sorafenib, lenvatinib, or atezolizumab-bevacizumab with reliable safety. In addition, the combination of two or more molecularly targeted therapies (first- plus second-line) has become a hot topic recently and is now being extensively investigated in patients with advanced HCC. In addition, a few biomarkers have been investigated and found to predict drug susceptibility and prognosis, which provides an opportunity to evaluate the clinical benefits of current therapies. In addition, many therapies other than tyrosine kinase inhibitors that might have additional survival benefits when combined with other therapeutic modalities, including immunotherapy, transarterial chemoembolization, radiofrequency ablation, hepatectomy, and chemotherapy, have also been examined. This review provides an overview on the current understanding of disease management and summarizes current challenges with and future perspectives on advanced HCC.

Interface engineering in NiSe2/Ni2Co/CoSe2 heterostructures encapsulated in hollow carbon shells for high-rate Li-Se batteries.

The sluggish conversion reaction and the accompanying huge volume fluctuation greatly hinder the application of lithium-selenium (Li-Se) batteries. Therefore, reasonably constructing stable carbonaceous hosts with efficient electrochemically active sites is particularly essential for promoting the development of Se cathodes. Herein, a metal-organic solid derived carbon host with multiple heterogeneous NiSe2/Ni2Co/CoSe2 interfaces was fabricated via in situ selenization. The formation of multiple heterointerfaces introduced subtle atomic array distortions, which provided additional electrochemically active sites compared with single heterointerfaces. Besides, the establishment of a built-in electric field was favorable for electron transfer and the absorption of Li+, thereby accelerating the reaction kinetics. Depending on the hollow structure and the heterogeneous catalysts, Li-Se batteries with NiSe2/Ni2Co/CoSe2@Se cathodes delivered reversible capacities of 503 and 324 mA h g-1 after 900 and 2200 cycles at 1 and 12 C, respectively. This work revealed the synergistic mechanism of multiple heterostructures composed of a Ni2Co alloy and in situ derived bimetallic selenides for Se cathodes and provided new insights into the exploitation of energy storage materials.

Cytokeratin 18 can help predict liver fibrosis in HCV infected patients with type 2 diabetes mellitus.

BACKGROUND: To investigate the predictive values of cytokeratin 18 for liver fibrosis in hepatitis C virus (HCV) infected patients with type 2 diabetes mellitus (T2DM). METHODS: 252 HCV-infected patients with T2DM between January 2012 and August 2017 were retrospectively reviewed. Pearson/spearman correlation analysis was used to detect the correlation in the entire cohort. Multivariate linear regression was used to identify independent predictors and logistic regression was for establishing models. Combination models that incorporated CK18 and other methods (i.e. transient elastography, aspartate transaminase-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4)] were developed in a training cohort of 132 patients. Performance of models was evaluated through discrimination ability and clinical benefits. An internal validation was conducted in 120 consecutive patients. RESULTS: CK18 was found significantly associated with fibrosis scores (r = 0.452, P < .001). CK18 and albumin were confirmed as independent predictors for fibrosis. For predicting significant fibrosis in the validation cohort, the observed AUC values of APRI + CK18 (AUC 0.83) and FIB-4 + CK18 (AUC 0.84) were higher than those of APRI (AUC 0.61) and FIB-4 (AUC 0.65). For predicting advanced fibrosis and cirrhosis, the AUC values of FIB-4 + CK18 (AUC 0.74 and 0.77, respectively) were significantly higher than those of FIB-4 (AUC 0.61 of both). Decision curve analysis confirmed the more clinical benefits can be provided by being combined with CK18. CONCLUSIONS: CK18 is an independent predictor of liver fibrosis for HCV-infected patients with T2DM. Noninvasive methods incorporate CK18 and other biomarker indices can have better performance for diagnosing fibrosis and help clinical decision-making.

Gold nanoparticles-mediated fluorescent chemical nose sensor for pathogenic diagnosis and phenotype.

Pathogens are one of the important factors affecting national economic construction. An ideal detection system for pathogen control with excellent sensitivity, high specificity, and time-saving is needed. Here, we reported a method for bacterial detection using gold nanoparticles-mediated fluorescent "chemical nose" sensors (GFCEs). The technique consists of gold nanoparticles-coated magnetic particle using benzaldehyde, octyl aldehyde, and pyrimidine-4-formaldehyde modified, respectively. And these positively charged nanocompound interacting with three different fluorescent proteins (FPs) to form three kinds of GFCEs, respectively, named GFCE1, GFCE2, and GFCE3. Upon binding with pathogenic cells, functionalized gold nanoparticles could identify patches on hydrophobic/functional surfaces of microorganisms, and self-assemble with living bacteria by complementary electrostatic interactions. The binding ability between GFCEs and bacteria determines the change of fluorescence response of three FPs from GFCEs. These feature fluorescent level are pathogen-specific, highly repeatable, and can be analyzed by Linear Discriminant Analysis (LDA). The combination of GFCE1 and GFCE2 has the best performance when detecting pathogens with concentrations of 106 cfu mL-1 . The first discriminant within 15 minutes is 93.8%, which could be used for subsequent identification of unknown samples. The commonly applicable system provides a simple way for the rapid bacterial detection without preprocessing procedures.

Different binding characteristics of ciprofloxacin to iron mineral surfaces: Thermodynamic evidence and site energy distribution analysis.

Iron minerals in soil play an important role in controlling the migration of fluoroquinolones. In this study, batch experiments were carried out to investigate interactions in ciprofloxacin (CIP) adsorption to goethite, hematite, and magnetite at pH 6.0. Thermodynamics and the site energy distribution theory (SEDT) were adopted to clarify the complexation types. Using the adsorption results, pH-dependent interactions were qualitatively elucidated. The thermodynamic data revealed the difference in adsorption mechanisms. With increasing sorbate loading, CIP adsorption to hematite and magnetite was endothermic, and both enthalpy change and entropy change decreased; however, CIP sorption to goethite showed opposite characteristics. The higher adsorption capacity and affinity of CIP to hematite and magnetite than those to goethite were caused by their higher site energy of the highest occurring frequency (E0 * ) and the temperature-dependent average site energy, respectively. The E0 * on the surface of goethite was about 17-19 kJ mol-1 , where E0 * values of hematite and magnetite were 20-26 kJ mol-1 . When temperature increased from 289.15 to 308.15 K, the high- and low-energy site densities for three iron minerals changed by -32 to 167% and by -36 to 223%, respectively. The different thermodynamic and SEDT results indicated that CIP adsorption mechanisms to goethite and hematite/magnetite were mainly outer- and inner-sphere complexation, respectively. The findings of this study reveal the adsorption mechanisms and are helpful in evaluating the transport of antibiotics in soils containing typical iron minerals.

CX3CR1 might be a promising predictor of systemic lupus erythematosus patients with pulmonary fibrosis.

The inflammatory process in systemic lupus erythematosus (SLE) affects many organs including the lungs. Chemokines are suggested to play important roles in the pathogenesis of SLE with pulmonary fibrosis (PF). In the present study, our objective is to evaluate the correlation between chemokines and PF in SLE patients. Transcriptome sequencing analysis was used to find the different expressed genes between SLE patients with PF and without PF. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of chemokines in SLE patients and healthy controls. Expression of CX3CR1 was measured by real-time polymerase chain reaction (PCR) and flow cytometer. Sixteen differentially chemokine genes were found to be associated to SLE with PF. Meanwhile, the upregulation of C-X3-C motif chemokine receptor 1 (CX3CR1) and its ligand, CX3C chemokine ligand 1 (CX3CL1) were observed in SLE patients with PF than that of SLE patients without PF and healthy control. Phenotypic analysis also showed that the surface expression of CX3CR1 increased in PBMCs from SLE patients with PF. Our observations indicated that CX3CL1/CX3CR1 axis is associated with PF in SLE. CX3CR1 might be a promising predictor of SLE with PF and the interactions between CX3CL1 and CX3CR1 might provide potential candidate target for the treatment of SLE with PF.

Identification of new potential antigen recognized by γδT cells in hepatocellular carcinoma.

In recent years, the application of chimeric antigen receptor T-cell (CAR-T) therapy based on gamma delta T (γδT) cells in hepatocellular carcinoma (HCC) immunotherapy has attracted more and more attention. However, specific antigens recognized by γδT cells are rarely identified, which has become the main restriction on such therapeutic application of γδT cells. In this report, we identified a new peptide and protein antigen recognized by γδT cells in HCC using our previous established strategy. First, we investigated the diversity of the γ9/δ2 T-cell immunorepertoire by sequence analyses of the expressed complementarity-determining region 3 (CDR3) in HCC patients. Then, we constructed γ9/δ2 T-cell receptor (TCR)-transfected cell lines expressing significant HCC CDR3 sequence and identified a series of peptides capable of binding to γδT cells specifically. Next, we identified, further tested and verified the biological functions of these peptides and their matched protein by bioinformatics analysis. We identified that the new protein hepatocyte growth factor-like protein, also called as macrophage-stimulating protein (MSP), and peptide HP1, not only bound to HCC-predominant γδTCR but also effectively activated γδT cells isolated from HCC patients. Moreover, they could stimulate γδT cells in peripheral blood from HCC patients to produce cytokines, which contributed to inhibiting HCC and played an important role in mediating cytotoxicity to HCC cell lines. In conclusion, we identified MSP and HP1, which showed potential as candidates for antigens recognized by γδT cells in HCC.

In Situ Self-Polymerization to Form Hollow Graphitized Carbon Nanocages with Embedded Cobalt Nanoparticles for High-Performance Lithium-Sulfur Batteries.

Lithium-sulfur batteries, owing to the multi-electron participation in the redox reaction, possess enormous energy density, which has aroused much attention. Nevertheless, the detrimental shuttle effect, volume expansion, and electrical insulation of sulfur, have hindered their application. To improve the cyclability, a functional host, consisting of Co nanoparticles and N-doped hollow graphitized carbon (Co-NHGC) material, is elaborated, which has the advantages of: 1) the graphitized carbon material working as an electronic matrix to improve the utilization rate of sulfur; 2) the hollow structure relieving the stress change caused by volume expansion; 3) the rich active sites catalyze the electrochemical reaction of sulfur and entrap polysulfides. These advantages significantly improve the performance of the lithium-sulfur batteries. Accordingly, the S@Co-NHGC cathode exhibits excellent initial specific capacity, high coulombic efficiency, and excellent rate performance. This work utilizes a novel method of dopamine in situ etching of a metal-organic framework to synthetize the Co-NHGC host of sulfur, which will hopefully provide inspiration for other energy materials.

Comparative transcriptome analysis reveals a potential role for CaMK4 in γδT17 cells from systemic lupus erythematosus patients with lupus nephritis.

γδ T cells may be involved in the onset of systemic lupus erythematosus (SLE) though the production of pro-inflammatory cytokines. IL-17 has been shown to play an important role in the pathogenesis of SLE with lupus nephritis (LN). Although some investigations have indicated that γδ T cells are the major producing cells of IL-17 (γδT17 cells), the function of γδT17 cells in SLE with LN has not yet been fully established. In the present study, transcriptome sequencing analysis was performed to identify genes in γδ T cells differentially expressed between SLE patients with LN and healthy subjects. We first showed that IL-17A expression level in SLE patients is higher than in healthy controls, and the most pronounced increase occurred in the SLE patients with LN. The population of γδ T cells was shown to be smaller in SLE patients, but there was no difference between SLE patients and controls with respect to γδT17 cells. Transcriptome sequencing analysis revealed 28 different genes associated with SLE disease among the γδ T cells from SLE patients with LN. In these genes, CaMK4 was further confirmed to be differently expressed in SLE patients. Finally, CaMK4 inhibitor was shown to inhibit the secretion of IL-17A in γδ T cells from SLE with LN. Our results suggest that CaMK4 may participate in the pathogenic mechanism of SLE with LN induced by γδT17 T cells. This constitutes evidence that CaMK4 inhibitors may serve as effective reagents in the treatment of SLE with LN.

Microcystin-LR in peripheral circulation worsens the prognosis partly through oxidative stress in patients with hepatocellular carcinoma.

Prognostic significance of serum microcystin in hepatocellular carcinoma has not been well investigated. The aim of the study was to reveal the relationship between serum microcystin-LR and prognosis in these patients. There were 650 early-stage hepatitis B-induced hepatocellular carcinoma patients, who were not affected by hepatitis C, cirrhosis, heavy drinking or excessive aflatoxin exposure. All of them underwent hepatectomy and were followed up for 5 years. Tumor relapse and overall death were recorded. Blood specimens were collected on admission and at the time of relapse. Serum levels of microcystin-LR and fluorescent oxidation products (FlOP_360, FlOP_320 and FlOP_400) were measured separately using enzyme-linked immunosorbent assay and fluorescence spectrometry. Multifactorial COX regression analysis suggested that serum microcystin-LR ≥ 0.97 ng/ml was associated with the increased risk of the tumor relapse (HR: 1.53, 95% CI: 1.35-1.77) and serum microcystin-LR ≥ 1.09 ng/ml was related to the higher risk of the overall death (HR: 1.58, 95% CI: 1.35-1.84) in the follow-up period. Furthermore, there was a linear relationship between serum level of microcystin-LR and serum levels of FlOP_360, FlOP_320 and FlOP_400 (P = 0.001, P = 0.023, P = 0.047). Serum levels of these fluorescent oxidation products were also higher in the patients with tumor relapse (P < 0.001, P < 0.001, P = 0.001) or overall death (P < 0.001, P = 0.001, P = 0.002) compared with the remaining patients. Serum microcystin-LR independently worsens the prognosis partly through promoting oxidative stress in patients with hepatocellular carcinoma.

Different sliding mechanics in space closure of lingual orthodontics: a translational study by three-dimensional finite element method.

Lingual orthodontics have become popular in modern society as they do not cause aesthetic impairment. From the translational medicine point of view, the use of biomechanical analysis to solve a clinical problem has rarely been reported. Here, we combined the clinical trial and 3-D finite element (FE) method to translate the clinical problem to the FE analysis and back to clinic. Twenty upper premolar extraction cases treated with customized lingual appliances were recruited in this study. Cephalometric films and cast records analysis showed that the "bowing effect", which is a major side effect in lingual orthodontics, occurred during the first treatment stage with single lingual cable retraction. In order to translate the problem to biomechanical research, we introduced the 3-D finite element (FE) model of a customized lingual orthodontic system. The 3-D FE model including the maxilla, periodontal ligament (PDL), and dentition was constructed from human computed tomography data. The tendency of tooth movements in three dimensions and stress distribution in the PDL were analyzed by different mechanical loading methods. 3-D FE analysis confirmed the "bowing effects" and unexpected tooth movements with application of single lingual retraction force. Interestingly, we found that applying forces on both buccal and lingual sides, called "double cable" mechanics, could prevent the "bowing effect". For the clinical trial, we applied the "double cable" force during space closure stage for 4 months, and confirmed "double cable" mechanics could correct and prevent the "bowing effect" clinically. Based on our results, both buccal and lingual forces should be used during space closure in lingual orthodontics to prevent and correct the "bowing effect". Moreover, the magnitude of buccal force should not be lower than the force on the lingual side.

Dentoskeletal and soft tissue changes associated with miniscrew anchorage in customized lingual orthodontics.

OBJECTIVES: The goal of this study was to analyze skeletal, dental, and soft tissue changes of patients treated with customized lingual systems and to evaluate the clinical effectiveness of miniscrew anchorage. METHODS: Nine upper first premolar extraction patients who were treated with customized lingual appliances were included in this study. Miniscrews were used for reinforcement of molar anchorage. Cephalometric films and study models were obtained before treatment (T1), after alignment (T2), and after treatment (T3). Treatment effects were analyzed by cephalometric radiographs and study models. RESULTS: The upper anterior teeth were retracted significantly at T2 and T3 (4.41 ± 4.14 mm and 5.51 ± 2.48 mm, respectively). During space closure, the upper first molars showed slight mesial movement (1.50 ± 1.97 mm). The intercanine width of the upper arch increased at T2 (1.59 ± 1.81 mm), but decreased at T3 (0.11 ± 1.00 mm). The sella-nasion-A, A-nasion-B, and mandibular plane angles were not significantly changed at T3. The upper lip showed continuous retraction at both T2 and T3 (1.40 ± 1.46 mm and 2.32 ± 2.48 mm, respectively). CONCLUSIONS: By using miniscrew anchorage for lingual orthodontics, patients' dental and soft tissue changes considerably improved and molar anchorage was reinforced.

Study on the Quality Evaluation of Compound Danshen Preparations Based on the xCELLigence Real-Time Cell-Based Assay and Pharmacodynamic Authentication.

Objective: To perform a preliminary study on the quality evaluation of compound Danshen preparations based on the xCELLigence Real-Time Cell-based Assay (RTCA) system and make a pharmacodynamics verification. Methods: The compound Danshen was discussed as a methodological example, and the bioactivity of the compound Danshen preparations were evaluated by real-time cell electronic analysis technology. Meanwhile, an in vivo experiment on an acute blood stasis rat model was performed in order to verify this novel evaluation through the curative effect of dissipating blood stasis. Results: We determined the cell index (CI) and IC50 of the compound Danshen preparations and produced time/dose-dependent cell response profiles (TCRPs). The quality of the three kinds of compound Danshen preparations was evaluated through the RTCA data. The trend of CI and TCRPs reflected the effect of drugs on the cell (promoting or inhibiting), and it was verified that the results correlated with the biological activity of the drugs using a pharmacodynamics experiment. Conclusion: The RTCA system can be used to evaluate the quality of compound Danshen Preparations, and it can provide a new idea and new method for quantitatively characterizing the biological activity of traditional Chinese medicines (TCMs).

Magnetic γ'-Fe4 N/Fe3 C, χ-Fe5 C2 , and θ-Fe3 C by a Simple Route for Application as Electrochemical Catalysts.

A new and simple method to fabricate magnetic Fe4 N/Fe3 C samples is reported. Meanwhile, pure phase iron carbides (θ-Fe3 C and χ-Fe5 C2 ) were obtained by controlling experimental conditions. The structures, magnetic properties, and morphology of the samples were investigated according to the generalized analysis of X-ray diffraction, X-ray photoelectron spectroscopy, as well as transmission electron microscopy and vibrating sample magnetometry. The magnetic properties measurement revealed the remarkable magnetic properties of the samples at 2 and 300 K. The application of the prepared samples as catalysts for oxygen evolution reaction was also investigated in alkaline solution. This simple and convenient route provides a new path to fabricate other metal nitrides and carbides.

Miniscrew-assisted customized lingual appliances for predictable treatment of skeletal Class II malocclusion with severe deep overbite and overjet.

This report describes the use of miniscrew-assisted customized lingual fixed appliances in a patient with severe skeletal Class II malocclusion. The patient was a 12-year-old Chinese girl with the chief complaint of protrusive lips and anterior teeth. Her diagnosis included a skeletal Class II relationship with maxillary protrusion, a backward-rotated mandible, a full Angle Class II molar relationship, and severe deep overjet and overbite. Four premolars were extracted, and miniscrew anchorage was placed in the maxillary posterior lingual segment to provide maximum anchorage and to achieve vertical control of the intruding molars. The customized lingual fixed appliance and temporary anchorage devices created a smooth and invisible treatment progress, resulting ultimately in a well-aligned dentition with ideal intercuspation and a dramatically improved profile. The 3-year follow-up examination indicated that the excellent treatment outcome was stable.

Nonsurgical correction using miniscrew-assisted vertical control of a severe high angle with mandibular retrusion and gummy smile in an adult.

Orthodontic treatment in adult patients with a skeletal discrepancy can be challenging. In this case report, we achieved both sagittal and vertical control by combining the classic sliding mechanics straight-wire technique with miniscrew anchorage. We treated a 21-year-old Chinese woman with a severe high mandibular plane angle, a retrusive chin, and a gummy smile. Her diagnosis included a skeletal Class II skull base with a mild anterior open bite, a protrusive maxilla, and a backwardly rotated mandible. This case underscores the importance of anchorage control in both the sagittal and vertical directions. First, we used miniscrews in the maxillary and mandibular buccal segments to obtain rigid anchorage. Next, we achieved good anterior and posterior vertical control with miniscrews in the maxillary anterior labial and posterior buccolingual segments. Intrusion of the maxillary molars contributed to deepening of the anterior overbite and counterclockwise rotation of the mandibular plane, which, in turn, improved the facial profile. Intrusion of the maxillary incisors contributed to correction of the gummy smile. After 1 year of retention, the patient had a stable, well-aligned dentition with ideal intercuspation and an improved facial contour. Our results thus suggest that placement of miniscrews in the anterior and posterior regions of the maxilla is effective for camouflaging a high-angle skeletal Class II defect. This technique requires minimal patient compliance and is particularly useful for correction of a high angle in an adult with a gummy smile.