ObjectiveSystemic lupus erythematosus (SLE), an autoimmune disorder, has been associated with nearly 100 susceptibility loci. Nevertheless, these loci only partially explain SLE heritability and their putative causal variants are rarely prioritised, which make challenging to elucidate disease biology. To detect new SLE loci and causal variants, we performed the largest genome-wide meta-analysis for SLE in East Asian populations.MethodsWe newly genotyped 10 029 SLE cases and 180 167 controls and subsequently meta-analysed them jointly with 3348 SLE cases and 14 826 controls from published studies in East Asians. We further applied a Bayesian statistical approach to localise the putative causal variants for SLE associations.ResultsWe identified 113 genetic regions including 46 novel loci at genome-wide significance (p<5×10−8). Conditional analysis detected 233 association signals within these loci, which suggest widespread allelic heterogeneity. We detected genome-wide associations at six new missense variants. Bayesian statistical fine-mapping analysis prioritised the putative causal variants to a small set of variants (95% credible set size ≤10) for 28 association signals. We identified 110 putative causal variants with posterior probabilities ≥0.1 for 57 SLE loci, among which we prioritised 10 most likely putative causal variants (posterior probability ≥0.8). Linkage disequilibrium score regression detected genetic correlations for SLE with albumin/globulin ratio (rg=−0.242) and non-albumin protein (rg=0.238).ConclusionThis study reiterates the power of large-scale genome-wide meta-analysis for novel genetic discovery. These findings shed light on genetic and biological understandings of SLE.
Saliva, which contains biological information, is considered a valuable diagnostic tool for local and systemic diseases and conditions because, similar to blood, it contains important molecules like DNA, RNA, and proteins. Exosomes are cell-derived vesicles 30-100 nm in diameter with substantial biological functions, including intracellular communication and signalling. These vesicles, which are present in bodily fluids, including saliva, are released upon fusion of multivesicular bodies (MVBs) with the cellular plasma membrane. Salivary diagnosis has notable advantages, which include noninvasiveness, ease of collection, absence of coagulation, and a similar content as plasma, as well as increased patient compliance compared to other diagnostic approaches. However, investigation of the roles of salivary exosomes is still in its early years. In this review, we first describe the characteristics of endocytosis and secretion of salivary exosomes, as well as database and bioinformatics analysis of exosomes. Then, we describe strategies for the isolation of exosomes from human saliva and the emerging role of salivary exosomes as potential biomarkers of oral and other systemic diseases. Given the ever-growing role of salivary exosomes, defining their functions and understanding their specific mechanisms will provide novel insights into possible applications of salivary exosomes in the diagnosis and treatment of systemic diseases.
Background:The accuracy of three-dimensional (3D) reconstructions from cone-beam computed tomography (CBCT) has been particularly important in dentistry, which will affect the effectiveness of diagnosis, treatment plan, and outcome in clinical practice. The aims of this study were to assess the linear, volumetric, and geometric accuracy of 3D reconstructions from CBCT and to investigate the influence of voxel size and CBCT system on the reconstructions results.Methods:Fifty teeth from 18 orthodontic patients were assigned to three groups as NewTom VG 0.15 mm group (NewTom VG; voxel size: 0.15 mm; n = 17), NewTom VG 0.30 mm group (NewTom VG; voxel size: 0.30 mm; n = 16), and VATECH DCTPRO 0.30 mm group (VATECH DCTPRO; voxel size: 0.30 mm; n = 17). The 3D reconstruction models of the teeth were segmented from CBCT data manually using Mimics 18.0 (Materialise Dental, Leuven, Belgium), and the extracted teeth were scanned by 3Shape optical scanner (3Shape A/S, Denmark). Linear and volumetric deviations were separately assessed by comparing the length and volume of the 3D reconstruction model with physical measurement by paired t-test. Geometric deviations were assessed by the root mean square value of the imposed 3D reconstruction and optical models by one-sample t-test. To assess the influence of voxel size and CBCT system on 3D reconstruction, analysis of variance (ANOVA) was used (α = 0.05).Results:The linear, volumetric, and geometric deviations were −0.03 ± 0.48 mm, −5.4 ± 2.8%, and 0.117 ± 0.018 mm for NewTom VG 0.15 mm group; −0.45 ± 0.42 mm, −4.5 ± 3.4%, and 0.116 ± 0.014 mm for NewTom VG 0.30 mm group; and −0.93 ± 0.40 mm, −4.8 ± 5.1%, and 0.194 ± 0.117 mm for VATECH DCTPRO 0.30 mm group, respectively. There were statistically significant differences between groups in terms of linear measurement (P < 0.001), but no significant difference in terms of volumetric measurement (P = 0.774). No statistically significant difference were found on geometric measurement between NewTom VG 0.15 mm and NewTom VG 0.30 mm groups (P = 0.999) while a significant difference was found between VATECH DCTPRO 0.30 mm and NewTom VG 0.30 mm groups (P = 0.006).Conclusions:The 3D reconstruction from CBCT data can achieve a high linear, volumetric, and geometric accuracy. Increasing voxel resolution from 0.30 to 0.15 mm does not result in increased accuracy of 3D tooth reconstruction while different systems can affect the accuracy.
ObjectiveWhether the orthodontic treatment with premolar extraction and maximum anchorage in adults will lead to a narrowed upper airway remains under debated. The study aims to investigate the airway changes after orthodontic extraction treatment in adult patients with Class II and hyperdivergent skeletal malocclusion.Materials and MethodsThis retrospective study enrolled 18 adults with Class II and hyperdivergent skeletal malocclusion (5 males and 13 females, 24.1 ± 3.8 years of age, BMI 20.33 ± 1.77 kg/m2). And 18 untreated controls were matched 1:1 with the treated patients for age, sex, BMI, and skeletal pattern. CBCT images before and after treatment were obtained. DOLPHIN 11.7 software was used to reconstruct and measure the airway size, hyoid position, and craniofacial structures. Changes in the airway and craniofacial parameters from pre to post treatment were assessed by Wilcoxon signed rank test. Mann-Whitney U test was used in comparisons of the airway parameters between the treated patients and the untreated controls. Significant level was set at 0.05.ResultsThe upper and lower incisors retracted 7.87 mm and 6.10 mm based on the measurement of U1-VRL and L1-VRL (P < 0.01), while the positions of the upper and lower molars (U6-VRL, and L6-VRL) remained stable. Volume, height, and cross-sectional area of the airway were not significantly changed after treatment, while the sagittal dimensions of SPP-SPPW, U-MPW, PAS, and V-LPW were significantly decreased (P < 0.05), and the morphology of the cross sections passing through SPP-SPPW, U-MPW, PAS, and V-LPW became anteroposteriorly compressed (P <0.001). No significant differences in the airway volume, height, and cross-sectional area were found between the treated patients and untreated controls.ConclusionsThe airway changes after orthodontic treatment with premolar extraction and maximum anchorage in adults are mainly morphological changes with anteroposterior dimension compressed in airway cross sections, rather than a decrease in size.
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