Epigenetic-based combination therapy and liposomal codelivery overcomes osimertinib-resistant NSCLC via repolarizing tumor-associated macrophages.

Osimertinib (Osi) is widely used as a first-line treatment for non-small cell lung cancer (NSCLC) with EGFR mutations. However, the majority of patients treated with Osi eventually relapse within a year. The mechanisms of Osi resistance remain largely unexplored, and efficient strategies to reverse the resistance are urgently needed. Here, we developed a lactoferrin-modified liposomal codelivery system for the combination therapy of Osi and panobinostat (Pan), an epigenetic regulator of histone acetylation. We demonstrated that the codelivery liposomes could efficiently repolarize tumor-associated macrophages (TAM) from the M2 to M1 phenotype and reverse the epithelial-mesenchymal transition (EMT)-associated drug resistance in the tumor cells, as well as suppress glycolysis, lactic acid production, and angiogenesis. Our results suggested that the combination therapy of Osi and Pan mediated by liposomal codelivery is a promising strategy for overcoming Osi resistance in NSCLC.

Evaluating anchorage and torque control in adolescent patients with Class II Division 1 malocclusion among 3 appliances.

INTRODUCTION: The objective of this study was to compare the differences in anchorage and torque control among the Tweed edgewise, Roth, and physiological anchorage Spee-wire systems (PASS) appliances (Zhejiang Xinya Technology Co, Ltd, Hangzhou, China). METHODS: A sample of 90 adolescent patients with Angle Class II Division 1 malocclusion (30 Tweed edgewise appliances, 30 Roth appliances, and 30 PASS appliances) with maximum anchorage requirements in the maxilla were collected for this study. The pretreatment baseline levels of the 3 groups were compared initially, and then the differences between the 3 appliances in anchorage and torque control were analyzed after superimposing the pretreatment and posttreatment lateral cephalograms and maxillary 3-dimensional (3D) digital models, respectively. RESULTS: There was no statistical difference in the pretreatment baseline levels of 3 groups, including gender, age, sagittal skeletal types (ANB), vertical skeletal types (SN-GoGn), anchorage requirements, and occlusal plane inclination (SN-OP). After superimposing the pretreatment and posttreatment lateral cephalograms and 3D digital models, respectively, no statistical differences were observed between the measurement results obtained from lateral cephalograms and 3D digital models. Among the measurement variables assessed in this study, statistical differences were observed in the mesial displacement of maxillary first molars, the incisor retraction, and the torque variation of maxillary central incisors among the 3 groups. Specifically, the Tweed group exhibited lower mesial displacement of maxillary first molars compared with the PASS and Roth groups. Furthermore, the Tweed group exhibited the greatest amount of incisor retraction and torque variation of maxillary central incisors, followed by the Roth group and then the PASS group. The remaining measurement variables for the 3 groups showed no statistical differences, including vertical variation of maxillary first molars and central incisors, torque variation of maxillary first molars and canines, mesiodistal inclination variation of maxillary first molars and canines, width variation between maxillary first molars, and width variation between maxillary canines. CONCLUSIONS: Compared with contemporary preadjusted straight wire appliances, the Tweed edgewise appliance has superiority in molar anchorage control. In contrast, compared with the Roth appliances, the PASS appliances without any auxiliary anchorage devices could make full use of physiological anchorage to achieve adequate control of molar anchorage. Clinical orthodontists may need to pay extra attention to physiological anchorage. The difference in torque control varies depending on the respective characteristics of bracket designs.

Network analysis of three-dimensional hard-soft tissue relationships in the lower 1/3 of the face: skeletal Class I-normodivergent malocclusion versus Class II-hyperdivergent malocclusion.

BACKGROUND: The determining effect of facial hard tissues on soft tissue morphology in orthodontic patients has yet to be explained. The aim of this study was to clarify the hard-soft tissue relationships of the lower 1/3 of the face in skeletal Class II-hyperdivergent patients compared with those in Class I-normodivergent patients using network analysis. METHODS: Fifty-two adult patients (42 females, 10 males; age, 26.58 ± 5.80 years) were divided into two groups: Group 1, 25 subjects, skeletal Class I normodivergent pattern with straight profile; Group 2, 27 subjects, skeletal Class II hyperdivergent pattern with convex profile. Pretreatment cone-beam computed tomography and three-dimensional facial scans were taken and superimposed, on which landmarks were identified manually, and their coordinate values were used for network analysis. RESULTS: (1) In sagittal direction, Group 2 correlations were generally weaker than Group 1. In both the vertical and sagittal directions of Group 1, the most influential hard tissue landmarks to soft tissues were located between the level of cemento-enamel junction of upper teeth and root apex of lower teeth. In Group 2, the hard tissue landmarks with the greatest influence in vertical direction were distributed more forward and downward than in Group 1. (2) In Group 1, all the correlations for vertical-hard tissue to sagittal-soft tissue position and sagittal-hard tissue to vertical-soft tissue position were positive. However, Group 2 correlations between vertical-hard tissue and sagittal-soft tissue positions were mostly negative. Between sagittal-hard tissue and vertical-soft tissue positions, Group 2 correlations were negative for mandible, and were positive for maxilla and teeth. CONCLUSION: Compared with Class I normodivergent patients with straight profile, Class II hyperdivergent patients with convex profile had more variations in soft tissue morphology in sagittal direction. In vertical direction, the most relevant hard tissue landmarks on which soft tissue predictions should be based were distributed more forward and downward in Class II hyperdivergent patients with convex profile. Class II hyperdivergent pattern with convex profile was an imbalanced phenotype concerning sagittal and vertical positions of maxillofacial hard and soft tissues.

Quantification and visualization of the tooth extraction effects on face with spatially dense geometric morphometrics.

PURPOSE: To apply geometric morphometrics and multivariate statistics to evaluate changes of the face for female Chinese patients who underwent orthodontic treatment with different type of anchorage control. METHODS: Forty-six adult female patients were enrolled including 33 four first premolar extraction cases (17 patients with mini-implants for maximum anchorage control and 16 patients without mini-implants) and 13 non-extraction cases with minimum treatment duration of 15 months. Spatially dense correspondence was established among all the images The pre-and post-treatment average faces of the two extraction groups and the non-extraction group were generated. Partial least squares regression was used to test the statistical significance of the effects of treatment for different anchorage choice. RESULTS: The upper and lower lips were retruded significantly after treatment in the extraction groups. In the maximum anchorage control group, the temple and cheek were depressed by approximately 1 mm, and the zygomatic regions were increased in the mid-face. However, these changes were not statistically significant. In comparison, no statistically significant facial changes occurred in the non-extraction group. CONCLUSIONS: The anchorage choice and the removal of four first premolar extraction influence lip shape as well as the perioral regions. However, extraction treatment does not impact the appearance of the cheeks and temples on a statistically level, as compared to orthodontic treatment without premolar extractions. Spatially dense geometric morphometric facilitates comprehensive treatment effect quantification and visualization on the full facial changes for improving orthodontic outcome evaluation.

Subjective and objective analysis of orthodontic expert consensus on the assessment of orthodontic treatment outcomes.

OBJECTIVE: The objective of the study was to explore and validate the consensus of orthodontic experts on the assessment of orthodontic treatment outcomes based on subjective and objective analysis. MATERIALS AND METHODS: The research consisted of two parts: the exploration and verification of expert consensus. First, a sample of 108 cases randomly selected from six dental schools in China were evaluated by 69 orthodontic experts and measured by researchers based on post-treatment study casts and lateral cephalograms, respectively. Then, through statistical analysis, the objective indicators significantly correlated with experts' subjective evaluations were selected, their weights were determined, and the critical values of satisfactory, acceptable and unacceptable grades were screened. Subsequently, another sample of 72 cases were evaluated by another 36 orthodontic experts, and the subjective evaluation results were compared with the objective measurement results. RESULTS: There were six model indicators and seven cephalometric indicators being significantly correlated with the experts' subjective evaluations, including occlusal contact, overjet, midline, interproximal contact, alignment, occlusal relationship, L1/NB, ANB, SN/OP, U1/SN, LL-EP, Cm-Sn-UL and Ns-Prn-Pos, with a cumulative R2 of 0.704. In the verification part, the correlation coefficient between the 36 experts' subjective scores and objective regression scores was 0.716 (P < .001); the correlation coefficient between the 36 experts' subjective grades and objective grades was 0.757 (P < .001). CONCLUSIONS: Orthodontic experts had good consistency in the subjective evaluation of the combined records of post-treatment study casts and lateral cephalograms. The objective indicators selected from subjective and objective analysis had good reliability and validity and could further improve the existing occlusal indices.

Accuracy of integration of dental cast and cephalograms compared with cone-beam computed tomography: a comparative study.

This study proposes a method that integrates maxillary dental cast and cephalograms and evaluates its accuracy compared with cone-beam computed tomography (CBCT) scans. The study sample comprised 20 adult patients with records of dental casts, cephalograms, and craniofacial CBCT scans. The maxillary dental cast was integrated with lateral and frontal cephalograms based on best-fit registration of palatal and dental outline curves from dental cast with cephalogram tracings. Linear measurement was conducted to assess the intra- and inter-examiner reproducibility of the proposed integration method using intraclass correlation coefficients; linear and angular measurements were conducted to assess its accuracy with CBCT scans as a standard reference. Paired t test, one sample t test, and mean ± standard deviation of the absolute value of difference were used to compare the integrated images and CBCT. The integration method showed good intra- and inter-examiner reproducibility (intraclass correlation coefficients > 0.98). The differences in linear and angular measurements between the integrated images and CBCT were not statistically significant but with a large deviation. When absolute value of difference was computed, the linear distance error was 0.51 ± 0.34 mm, the tooth point coordinate errors in X, Y and Z axes were 0.22 ± 0.22, 0.38 ± 0.32 and 0.21 ± 0.21 mm, respectively; the angular error in pitch, roll and yaw of the dental cast was 0.82 ± 0.51, 0.92 ± 0.59 and 0.80 ± 0.41 degree, respectively. The proposed method for integration of dental cast and cephalograms showed good reproducibility and acceptable accuracy compared with CBCT. It could be helpful for researchers to study three-dimensional tooth growth changes using the existing craniofacial growth data especially cephalograms.

Orthodontic treatment of substituting third molars for missing permanent molars.

INTRODUCTION: This study aimed to evaluate the orthodontic effect and efficiency of substituting third molars for missing first or second permanent molars systematically. METHODS: Forty-six patients (69 third molars total) with missing permanent molars replaced by third molars were selected. The angulation, crown-to-root ratio, and periodontal condition of the third molars before and after treatment were compared. The American Board of Orthodontics Objective Grading System was used to evaluate the alignment and occlusion of third molars after treatment. The duration of orthodontic treatment and third molar replacement therapy were also recorded. RESULTS: The average orthodontic treatment time was 33.9 ± 5.6 months, and the average angulation change of third molars during treatment was 49.8 ± 29.8°. The average height of mesial alveolar bone increased by 4.8 ± 0.5 mm in patients whose third molars were mesially inclined or horizontally impacted. The root length of adult patients decreased by 0.72 ± 0.02 mm on average, and the average gingival recession was 0.10 mm, both of which were not statistically significant. The average score for each third molar evaluated by the American Board of Orthodontics Objective Grading System was 1.8 ± 0.5 points. CONCLUSIONS: If the indications and timing of treatment were well-controlled, third molars would be excellent substitutes for missing first or second permanent molars through the orthodontic method.

Early and 1-year postsurgical stability and its factors in patients with complicated skeletal Class â ¢ malocclusion treated by conventional and surgery-first approach: A prospective cohort study.

INTRODUCTION: This study aimed to compare postsurgical stability between conventional (CSA) and surgery-first (SFA) approaches and investigate its prognostic factors in patients with a skeletal Class Ⅲ extraction. METHODS: Twenty and 19 patients treated with LeFort I osteotomy and bilateral sagittal split ramus osteotomy (BSSRO) with premolar extraction were enrolled in SFA and CSA groups, respectively. Serial cone-beam computed tomography images obtained before surgery, immediately after surgery (T1), 3 months after surgery, and 12 months after surgery were used for 3-dimensional quantitative analysis. The condyle was segmented for analyzing volumetric changes. Repeated measures analysis of variance, independent t test, and chi-square test were used to compare time-course and intergroup differences. Pearson and Kendall correlation and multivariate linear regression analyses were used to explore prognostic factors affecting skeletal stability. RESULTS: In both CSA and SFA, postsurgical relapse mainly occurred in the mandible sagittal and vertical dimensions and during the first 3 months after surgery. Stability in SFA was significantly less than that in CSA. Intraoperatively, inferolateral condylar displacement with proximal segment inwards, clockwise rotation, and return movements after surgery were observed regardless of the treatment approach. The condylar volume remained stable over time. Multivariate regression analysis showed that posterior vertical dimension (VD) at T1 (-1.63 mm), surgical amount of mandibular setback (-10.33 mm), surgical condylar downwards displacement (-1.28 mm), and anterior overjet at T1 (6.43 mm) were the most important predictors of early mandibular relapse (r2 = 0.593). CONCLUSIONS: The risk of early relapse could be reduced by controlling the anterior, middle, and posterior constraints provided by the prediction model.

Perceptual difference of smile aesthetics between 2-dimensional photographs and 3-dimensional dentofacial images: a cross-sectional study.

BACKGROUND: The aim of this study was to compare the perceptual difference of smile aesthetics between 2D photographs and 3D dentofacial images as perceived by orthodontists and graduate students. METHODS: Forty-eight subjects finished orthodontic treatment were recruited with 2D photographs of frontal, oblique and lateral views as well as 3D dentofacial images. Twelve senior orthodontists and 13 postgraduate students were asked to rate the 2D and 3D smile simulations based on visual analog scale (VAS) and to vote for smile features that affect the attractiveness of smile. At the end, they completed a questionnaire about their views on different smile simulations. Wilcoxon signed-rank, Bland-Altman analysis, and multiple linear regression were used to compare the ratings and votes of smile perception between raters and between records. RESULTS: Orthodontists and postgraduate students rated smile consistently with 2D photographs, while orthodontists tended to give a higher rate for unattractive smiles and a lower rate for attractive smiles with 3D dentofacial images. The 3D dentofacial images were rated significantly lower than 2D photographs and the voting of most of the smile features showed significant negative main effect on VAS scores, while the effect of demographic characteristics of raters, voting on visible width of upper dentition and buccal corridor was not significant. In addition, a significant negative main effect of commissure and facial profile was found on the rating discrepancy between 2D and 3D images. CONCLUSIONS: Senior orthodontists tend to perceived 3D images more conservatively in smile evaluation. 3D dentofacial images were rated lower than 2D photographs and most of the smile features affect the aesthetic perception of smile. The perceptual difference of commissure and facial profile contributed to the lower ratings in 3D dentofacial images.

Natural reference structures for three-dimensional maxillary regional superimposition in growing patients.

BACKGROUND: Assessment of growth-related or treatment-related changes in the maxilla requires a reliable method of superimposition. Such methods are well established for two-dimensional (2D) cephalometric images but not yet for three-dimensions (3D). The aims of this study were to identify natural reference structures (NRS) for the maxilla in growing patients in 3D, opportunistically using orthodontic mini-screws as reference; and to test the applicability of the proposed NRS for maxillary superimposition by assessing the concordance of this approach with Björk's 'stable reference structures' in lateral projection. METHODS: The stability of the mini-screws was tested on longitudinal pairs of pre- and post-orthodontic cone-beam computed tomography (CBCT) images by measuring the distance changes between screws. After verifying the stability of the mini-screws, rigid registration was performed for aligning the stable mini-screws. Then, non-rigid registration was used to establish the dense voxel-correspondence among CBCT images and calculate the displacement of each voxel belonging to the maxilla relative to the mini-screws. The displacement vectors were transformed to a standardized maxillary template to categorize the stability of the internal structures statistically. Those voxels that displaced less relative to the mini-screws were considered as the natural reference structures (NRS) for the maxilla. Test samples included another dataset of longitudinal CBCT scans. They were used to evaluate the applicability of the proposed NRS for maxillary superimposition. We assessed whether aligning the maxilla with proposed NRS is in concordance with the maxillary internal reference structures superimposition in the traditional 2D lateral view as suggested by Björk. This was quantitively assessed by comparing the mean sagittal and vertical tooth movements for both superimposition methods. RESULTS: The stability of the mini-screws was tested on 10 pairs of pre- and post-orthodontic cone-beam computed tomography (CBCT) images (T1: 12.9 ± 0.8 yrs, T2: 14.8 ± 0.7 yrs). Both the loaded and the unloaded mini-screws were shown to be stable during orthodontic treatment, which indicates that they can be used as reference points. By analyzing the deformation map of the maxilla, we confirmed that the infraorbital rims, maxilla around the piriform foramen, the infrazygomatic crest and the hard palate (palatal vault more than  1 cm distal to incisor foramen except the palatal suture) were stable during growth. Another dataset of longitudinal CBCT scans (T1: 12.2 ± 0.63 yrs, T2: 15.2 ± 0.96 yrs) was used to assess the concordance of this approach with Björk's 'stable reference structures'. The movement of the maxillary first molar and central incisor showed no statistically significant difference when superimposing the test images with the proposed NRS or with the classic Björk maxillary superimposition in the lateral view. CONCLUSIONS: The infraorbital rims, maxilla around the piriform foramen, the infrazygomatic crest and the hard palate (palatal vault more than 1 cm posterior to incisal foramen except the palatal suture) were identified as stable regions in the maxilla. These stable structures can be used for maxillary superimposition in 3D and generate comparable results to Björk superimposition in the lateral view.

Nasal characteristics in patients with asymmetric mandibular prognathism.

INTRODUCTION: To objectively quantify nasal characteristics of patients with asymmetric mandibular prognathism and to evaluate the association between nasal asymmetry and dentofacial abnormalities. METHODS: Ninety adult patients with asymmetric mandibular prognathism were included. Images were captured during pretreatment using 3-dimensional stereophotogrammetry. A total of 7160 uniformly sampled quasi-landmarks were automatically identified on each facial image to establish correspondence using a template mapping technique. Fifteen commonly used anatomic landmarks were automatically located on each image through barycentric to Cartesian coordinate conversion. Nasal characteristics and asymmetry were quantified by anthropometric linear distances, angular measurements, and surface-based analysis. The degree of the nasal, chin, and periorbital asymmetry in a patient was scored using a root-mean-squared error between the left and right sides. The correlations among these regional asymmetries were evaluated. RESULTS: The nasal tip was significantly shifted to the deviated side of the chin, and the nostrils were asymmetrical. The location and degree of nasal asymmetry varied among patients with asymmetric mandibular prognathism. The level of nasal asymmetry was significantly and positively correlated with chin and periorbital asymmetry. CONCLUSIONS: Nasal asymmetry is present in asymmetric mandibular prognathism patients. Furthermore, it is positively associated with periorbital deviation and chin deviation. Individualized nasal asymmetry evaluation should be performed, and clinicians should inform patients about preexisting nasal asymmetry.

Automated assessment of mandibular shape asymmetry in 3-dimensions.

INTRODUCTION: This study aimed to develop an automatic pipeline for analyzing mandibular shape asymmetry in 3-dimensions. METHODS: Forty patients with skeletal Class I pattern and 80 patients with skeletal Class III pattern were used. The mandible was automatically segmented from the cone-beam computed tomography images using a U-net deep learning network. A total of 17,415 uniformly sampled quasi-landmarks were automatically identified on the mandibular surface via a template mapping technique. After alignment with the robust Procrustes superimposition, the pointwise surface-to-surface distance between original and reflected mandibles was visualized in a color-coded map, indicating the location of asymmetry. The degree of overall mandibular asymmetry and the asymmetry of subskeletal units were scored using the root-mean-squared-error between the left and right sides. These asymmetry parameters were compared between the skeletal Class I and skeletal Class III groups. RESULTS: The mandible shape was significantly more asymmetrical in patients with skeletal Class III pattern with positional asymmetry. The condyles were identified as the most asymmetric region in all groups, followed by the coronoid process and the ramus. CONCLUSIONS: This automated approach to quantify mandibular shape asymmetry will facilitate high-throughput image processing for big data analysis. The spatially-dense landmarks allow for evaluating mandibular asymmetry over the entire surface, which overcomes the information loss inherent in conventional linear distance or angular measurements. Precise quantification of the asymmetry can provide important information for individualized diagnosis and treatment planning in orthodontics and orthognathic surgery.

Facial asymmetry assessment in skeletal Class III patients with spatially-dense geometric morphometrics.

OBJECTIVE: Quantification and visualization of the location and magnitude of facial asymmetry is important for diagnosis and treatment planning. The objective of this study was to analyze the asymmetric features of the face for skeletal Class III patients using spatially-dense geometric morphometrics. METHODS: Three-dimensional facial images were obtained for 86 skeletal Class III patients. About 7160 uniformly sampled quasi-landmarks were automatically identified on each face using template mapping technique. The pointwise surface-to-surface distance between original and mirror face was measured and visualized for the whole face after robust Procrustes superimposition. The degree of overall asymmetry in an individual was scored using a root-mean-squared-error. Automatic partitioning of the face was obtained, and the severity of the asymmetry compared among seven facial regions. RESULTS: Facial asymmetry was mainly located on, but not limited to, the lower two-thirds of the face in skeletal Class III patients. The lower cheek and nose asymmetry were detected to have more extensive and of a greater magnitude of asymmetry than other facial anatomical regions but with various individual variations. The overall facial asymmetry index and the regional facial asymmetry indices were higher in males and patients with chin deviation. CONCLUSIONS: Soft tissue asymmetry is predominately presented in the lower-third of the face in skeletal Class III patients and with various variations on other facial anatomical regions. Morphometric techniques and computer intensive analysis have allowed sophisticated quantification and visualization of the pointwise asymmetry on the full face.

An epidemiological survey of gastroesophageal reflux disease at the digestive endoscopy center in Guangzhou.

OBJECTIVE: This study aims to investigate the detection rates, common symptoms and risk factors of gastroesophageal reflux disease (GERD), and laryngopharyngeal reflux disease (LPRD) at the digestive endoscopy center. METHODS: A multicenter cross-sectional survey conducted at three hospitals and a total of 565 eligible participants were enrolled. All the patients completed routine ENT examination, gastroscopy, gastroesophageal reflux questionnaire (GerdQ), reflux symptom index (RSI) and a self-designed 25-item symptoms table survey. RESULTS: Among the 565 eligible participants, the detection rates of GERD and LPRD were 18.41% (104/565) and 9.91% (56/565), respectively. The detection rate of GERD combined with LPRD was 3.19% (18/565). Among GERD and LPRD patients, males (vs. females), middle-aged and elderly patients (vs. young people), BMI ≥ 24.0 kg/m2 (vs. BMI < 24.0 kg/m2), with current smoking history (vs. no smoking), and current drinking history (vs. no drinking), lying down immediately after meal (vs. no lying down immediately after meal) were significantly higher (all p < 0.05). The most common extraesophageal symptoms in patients with GERD were dry mouth (66.35%), globus sensation (56.73%), dry throat and pharyngeal itching (55.77%). The most common extraesophageal symptoms in patients with LPRD were globus sensation (91.07%), dry throat and pharyngeal itching (83.93%), and dry mouth (82.14%). CONCLUSION: GERD and LPRD had a high detection rate at the digestive endoscopy center in Guangzhou, China. Older age, BMI ≥ 24.0 kg/m2, smoking and drinking history were risk factors for both GERD and LPRD. Neither GerdQ nor RSI scores included common extraesophageal symptoms.

Analysis of correlation of 3-dimensional lip vermilion morphology and dentoskeletal forms in young Chinese adults on the basis of sex and skeletal patterns.

INTRODUCTION: The objective of this research was to evaluate the correlation between 3-dimensional (3D) lip vermilion (LV) morphology and skeletal patterns as well as incisor measurements in young Chinese adults. METHODS: In all, 240 young adults were enrolled; these included 80 patients each with skeletal Class I, Class II, and Class III malocclusions, respectively. Each sagittal skeletal pattern included 40 male and 40 female subjects. Twenty-two 3D LV measurements were obtained from 3D facial scans. Skeletal and incisor measurements were evaluated on lateral cephalograms. Correlation and regression analysis were performed between soft and hard tissue measurements. RESULTS: Six of 22 LV measurements showed significant differences between male and female subjects. The 3D LV morphology showed significant differences with respect to different skeletal patterns and sex. Adults with skeletal Class III malocclusion tended to have thinner upper vermilion and fuller lower vermilion than subjects with skeletal Class II and III malocclusion. The mandibular plane angle negatively correlated with the upper-lower vermilion midsagittal curve length and surface area ratio in adults with skeletal Class I and II malocclusion, yet the vertical facial skeletal type showed no correlation in adults with skeletal Class III malocclusion. The vermilion angle, central bow angle, vermilion height, vermilion midsagittal curve length, vermilion height and width ratio, and vermilion surface area showed a significant correlation with incisor measurements. Regression analysis found that the ANB angle was an important factor affecting the upper and lower vermilion midsagittal curve length and surface area ratio. Further, the vermilion height and height and width ratio were closely correlated with the interincisal (U1/L1) angle, whereas the central bow angle was closely correlated with the maxillary incisor torque. CONCLUSIONS: Most LV morphology variables were correlated to skeletal patterns and incisor measurements. Skeletal Class III malocclusion showed significant differences in vermilion morphology. Both the sagittal and vertical skeletal pattern have effects on vermilion proportion. The incisor torque was closely correlated to vermilion shape and central bow angle and might influence the vermilion esthetics. However, the proportion of the upper and lower vermilion was mainly affected by the ANB angle.

Measuring orthodontic treatment impact: Description or judgment, challenge or result.

INTRODUCTION: Determination of improvement in orthodontic treatment may depend on the measurement method used and the purpose. METHODS: Improvement after orthodontic treatment (from T1 to T2 [beginning to end of treatment]) was assessed 3 ways from a set of 98 patient records: (1) calculated by subtracting judges' assessments at T2 from T1 for records presented in random order, (2) judged as a holistic impression viewing T1 and T2 records side by side, and (3) determined from proxies (American Board of Orthodontics Discrepancy Index, the American Board of Orthodontics Objective Grading System, and the Peer Assessment Rating index). RESULTS: High levels of intramethod consistency were observed, with intraclass correlation coefficient clustering around an intraclass correlation coefficient of 0.900, and distributions were normal. Calculated and judged improvements correlated at r = 0.606. Calculated or judged improvements were correlated at a lower level with proxies. Calculated improvement was significantly associated with "challenge" (T1) scores and judged improvement associated with "results" (T2) scores. Common method bias was observed, with higher correlations among similar indexes than among indexes at the same time that used various methods. Relative to differences in Peer Assessment Rating scores, calculated improvement overestimated low scores and underestimated high ones. The same effect, but statistically greater, was observed using direct judgment of improvement. CONCLUSIONS: These findings are consistent with decision science and measurement theory. In some circumstances, such as third-party reimbursement and research, operationally defined measures of occlusion are appropriate. In practice, the determination of occlusion and improvement are best performed by judgment that naturally corrects for biases in proxies and incorporates background information.

Designing of a novel polyvinylidene fluoride/TiO2/UiO-66-NH2 membrane with photocatalytic antifouling properties using modified zirconium-based metal-organic framework.

Novel polyvinylidene fluoride/TiO2/UiO-66-NH2 (PVDF/TiUN) membranes were produced by the delay phase separation method via introducing the TiO2/UiO-66-NH2 (TiUN) nanocomposite into PVDF casting solution. Interconnection of TiO2 and UiO-66-NH2 improved photocatalysis capacity and endowed PVDF/TiUN membranes with self-cleaning capability. Quantitative measurements showed that, firstly, PVDF/TiUN membranes exhibited improved photodegradation kinetics and efficiency (up to 88.1%) to Rhodamine B (RhB). Secondly, the performances of bovine serum albumin (BSA) rejection and permeation of PVDF/TiUN membranes outperformed those of other check samples, indicating enhanced hydrophilicity. Thirdly, rejection rate of BSA reached a breathtaking 98.14% and flux recovery ratio (FRR) of BSA reached a breathtaking 95.37%. Thus, given their excellent anti-contamination property and separation performance, the PVDF/TiUN membrane is very likely to be a novel water treatment membrane.

The three-dimensional stable mandibular landmarks in patients between the ages of 12.5 and 17.1 years.

BACKGROUND: With the aid of implants, Björk identified two-dimensional mandibular stable structures in cephalograms during facial growth. However, we do not know what the three-dimensional stable structures are with certainty. The purpose of this study was to identify the most stable mandibular landmarks in growing patients using three-dimensional images. METHODS: The sample was comprised of two cone-beam computed tomography (CBCT) scans taken about 4.6 years apart in 20 growing patients between the ages of 12.5 (T1) and 17.1 years (T2). After head orientation, landmarks were located on the chin (Pog), internal symphysis (Points C, D and E), and mandibular canals, which included the mental foramina (MF and MFA) and mandibular foramina (MdF). The linear distance change between Point C and these landmarks was measured on each CBCT to test stability through time. The reliability of the suggested stable landmarks was also evaluated. RESULTS: The total distance changes between Point C and points D, E, Pog, MF, and MFA were all less than 1.0 mm from T1 to T2. The reliability measures of these landmarks, which were measured by the Cronbach alpha, were above 0.94 in all three dimensions for each landmark. From T1 to T2, the distance changes from Point C to the right and left mandibular foramina were 3.39 ± 3.29 mm and 3.03 ± 2.83 mm, respectively. CONCLUSIONS: During a growth period that averaged 4.6 years, ranging from 11.2 to 19.8 years old, the structures that appeared relatively stable and could be used in mandibular regional superimpositions included Pog, landmarks on the inferior part of the internal symphysis, and the mental foramen. The centers of the mandibular foramina and the starting points of the mandibular canal underwent significant changes in the transverse and sagittal dimensions.

Highly Selective Capture of Monophosphopeptides by Two-Dimensional Metal-Organic Framework Nanosheets.

Separation of monophosphopeptides from multi-phosphopeptides in complex biological samples is significant in the study of protein kinase signal transduction pathways. To the best of our knowledge, very few materials have been reported that could selectively enrich monophosphopeptides because of the chemical difficulty in retaining the intermediate monophosphopeptides and excluding both non-phosphopeptides and multi-phosphopeptides in acidic conditions, which requires unique interactions to balance the metallic affinity and the hydrophobicity. With the large surface area, abundant accessible active sites, and ultrathin structures, two-dimensional (2-D) metal-organic framework (MOF) Hf-1,3,5-tris(4-carboxyphenyl)benzene (BTB) nanosheets were rationally selected. Due to the elongated organic ligands and the balance between metallic affinity of clusters and hydrophobicity from ligands, the 2-D Hf-BTB nanosheets exhibited unique enrichment selectivity toward monophosphopeptides. The 2-D MOF nanosheets demonstrated excellent sensitivity (detection limit of 0.4 fmol µL-1) and selectivity [1:1000 molar ratios of ß-casein/BSA (bovine serum albumin)] in model phosphopeptides enrichment. The nanosheets were implemented for the analysis of nonfat milk and human saliva samples as well as in situ isotope labeling for dysregulated phosphopeptides from patients' serum with anal canal inflammation, exhibiting 6.6-fold upregulation of serum phosphopeptide HS4 (ADpSGEGDFLAEGGGVR) compared to the control healthy serum. The proteomics analysis of mouse brain cortical samples associated with Alzheimer's disease, which were from Akt (protein kinase B) conditional knockout mouse and littermate control mouse, was further established with 2-D Hf-BTB nanosheets. With high capture efficiency for monophosphopeptides, this method was capable of distinguishing the difference of monophosphopeptides from microtubule-associated protein τ (MAPT/τ) between the Akt knockout sample and control sample.

The efficacy of RGD modified liposomes loaded with vinorelbine plus tetrandrine in treating resistant brain glioma.

Brain glioma is one of the most common and devastating intracranial malignancies with a high mortality. Chemotherapy for brain glioma is not ideal due to blood brain barrier (BBB) and multidrug resistance (MDR). The objectives of the present study were to develop a kind of RGD (Arg-Gly-Asp) tripeptide modified vinorelbine plus tetrandrine liposomes to achieve BBB transportation, MDR reversion and glioma cell targeting simultaneously. The studies were performed on glioma cells, resistant glioma cells and glioma-bearing mice. Results showed that the constructed liposomes with suitable physicochemical properties could significantly enhance the transport across BBB, obviously accumulate in glioma cells, and exhibit evident capabilities in diminishing brain glioma in mice. Action mechanism studies indicated that the enhanced anticancer efficacy could be attribute to the follows: prolonged elimination half-life (7.093 ± 1.311 h); increased AUC0-24 h (28.92 ± 2.66 mg/L*h); transporting across BBB; enhanced cellular uptake; down-regulation on P-gp (0.49 ± 0.06 fold); inducing apoptosis via activating caspase 8, 9, and 3 (2.40 ± 0.22, 3.57 ± 0.29, and 4.33 ± 0.30 folds, respectively). In conclusion, the RGD modified vinorelbine plus tetrandrine liposomes may offer a promising therapeutic strategy for treatment of brain glioma.