Vav2 promotes ductus arteriosus anatomic closure via the remodeling of smooth muscle cells by Rac1 activation.

The ductus arteriosus (DA), bridging the aorta and pulmonary artery, immediately starts closing after birth. Remodeling of DA leads to anatomic obstruction to prevent repatency. Several histological changes, especially extracellular matrices (ECMs) deposition and smooth muscle cells (SMCs) migration bring to anatomic closure. The genetic etiology and mechanism of DA closure remain elusive. We have previously reported a novel copy number variant containing Vav2 in patent ductus arteriosus (PDA) patients, but its specific role in DA closure remains unknown. The present study revealed that the expression of Vav2 was reduced in human patent DA, and it was less enrichment in the adjacent aorta. Matrigel experiments demonstrated that Vav2 could promote SMC migration from PDA patient explants. Smooth muscle cells with Vav2 overexpression also presented an increased capacity in migration and downregulated contractile-related proteins. Meanwhile, SMCs with Vav2 overexpression exhibited higher expression of collagen III and lessened protein abundance of lysyl oxidase, and both changes are beneficial to DA remodeling. Overexpression of Vav2 resulted in increased activity of Rac1, Cdc42, and RhoA in SMCs. Further investigation noteworthily found that the above alterations caused by Vav2 overexpression were particularly reversed by Rac1 inhibitor. A heterozygous, rare Vav2 variant was identified in PDA patients. Compared with the wild type, this variant attenuated Vav2 protein expression and weakened the activation of downstream Rac1, further impairing its functions in SMCs. In conclusion, Vav2 functions as an activator for Rac1 in SMCs to promote SMCs migration, dedifferentiation, and ECMs production. Deleterious variant potentially induces Vav2 loss of function, further providing possible molecular mechanisms about Vav2 in PDA pathogenesis. These findings enriched the current genetic etiology of PDA, which may provide a novel target for prenatal diagnosis and treatment. KEY MESSAGES: Although we have proposed the potential association between Vav2 and PDA incidence through whole exome sequencing, the molecular mechanisms underlying Vav2 in PDA have never been reported. This work, for the first time, demonstrated that Vav2 was exclusively expressed in closed DAs. Moreover, we found that Vav2 participated in the process of anatomic closure by mediating SMCs migration, dedifferentiation, and ECMs deposition through Rac1 activation. Our findings first identified a deleterious Vav2 c.701C>T variant that affected its function in SMCs by impairing Rac1 activation, which may lead to PDA defect. Vav2 may become an early diagnosis and an effective intervention target for PDA clinical therapy.

[Morphological characteristics of upper alveolar bone around central incisor in Class II division 1 and division 2 malocclusion on cone-beam CT].

PURPOSE: During orthodontic treatment, the incisors in patients with Class II division 1 and division 2 malocclusion showed different clinical features, which determine the different ways to move the teeth to the suitable position. This study analyzed the morphology of alveolar bone around upper central incisor with cone-beam CT (CBCT). METHODS: The sample consisted of 20 normal malocclusion and 40 patients with Class II malocclusion （division 1 20 cases and division 2 20 cases）. CBCT images before orthodontic treatment were reconstructed by INVIVO 5.0 image processing software. Paired t test was used for statistical analysis with SPSS 19.0 software package. RESULTS: At the upper central incisors, the alveolar thickness between normal malocclusion and Class II division 1 and division 2 malocclusion had significant difference except the palate thickness between normal malocclusion and Class II division 2 malocclusion (P<0.05). CONCLUSIONS: Orthodontist should consider the relationship between the teeth position and alveolar bone shape comprehensively, choose the correct plan in order to avoid root desorption, alveolar bone loss, fenestration and other adverse reactions.

[Comparison of condylar position between Angle Class I and Class II malocclusion in teenagers].

PURPOSE: To analyze and compare the difference of condylar position between Angle Class I and Class II malocclusion patients using cone-beam CT (CBCT). METHODS: Thirty Class I patients, 30 Class II division 1 patients and 30 Class II division 2 patients were selected in this study. Each patient underwent CBCT. The images in the oblique position perpendicular to the condyloid process were reconstructed by Examvision software. The joint space was measured by Exam Vision software. The data were processed with SPSS17.0 software package. RESULTS: The upper joint space was larger in Class II, the posterior joint space was smaller in Class II patients; and in Class II division 1 patients, both of the upper and anterior joint spaces were larger than in Class II division 2 patients，the differences were significant (P<0.05). The length of condyle was longer in Class I patients than in Class II patients. CONCLUSIONS: The condylar position in Class II division 2 patients was lower and further backward. The length of condyle is shortest in Class II division 2 patients.

[A study on the thickness of buccal bone in the mandible of different vertical facial type in adults using cone-beam CT].

PURPOSE: To provide some references of using micro-implant anchorage in clinical orthodontic treatment, the thickness of buccal bone of mandible of different vertical facial type in adults with cone-beam CT (CBCT) were measured. METHODS: Initial 3-dimensional images of 45 adult patients (15 men, 30 women)were reoriented by using a standardized protocol, and divided into 3 groups by angle of mandibular plane (G1: high angle, 15 patients; G2: average angle, 15 patients; G3: low angle, 15 patients). After signing the informed consent form, three measurement points were defined at 4, 6, and 8mm from the alveolar crest in each measurement area. Statistical analysis was performed with SPSS11.0 software package. RESULTS: The thickness of buccal bone in mandible was thinner in G1 than in G2, and was thinnest in G3. The cortical bone thickness was thickest at the 8 mm level and thinnest at the 4mm level. CONCLUSIONS: The study suggested that the cortical bone thickness at 4mm level from the alveolar crest was safe for implantation. It is more stable when the distance of implants was more away from the alveolar crest. Patients with low mandibular plane angle should use self-tapping micro-implant anchorage. Supported by Nantong Science and Technology Fund (HS2013033).

[Clinical effect of premolar extraction with high torque self-locking appliances].

PURPOSE: To analyze the clinical effect of extraction correction of patients with maxillary protrusion by using Damon high torque appliances. METHODS: Forty patients with extraction of four first premolars due to orthodontic treatment were selected. They had protrusion of maxilla and were randomly divided into two groups. Both arches of Damon group were treated with Damon high torque appliances and MBT group were corrected with traditional MBT straight wire appliance; patients in two groups received sliding mechanics for adduction of upper anterior teeth. Cephalometric radiophotographs were analyzed before（T0）and after adduction of upper anterior teeth（T1）. The difference between the two groups was analyzed with SPSS15.0 software package. RESULTS: The upper incisors showed a more retruded position in the two groups at T1,although they showed a similar amount in both groups. The backward movement of upper lip was 2.31mm in Damon group, which was significantly less than that of 2.81mm in MBT group(P<0.05). No significant difference in the first molar mesialization was detected between Damon group(2.33 mm) and MBT group(2.36mm) (P>0.05). For anterior teeth retraction, nasolabial angle (NLA) in MBT and Damon group were 107.44°and 106.33°, increase of NLA in MBT group was 9.17°,which was significantly larger than that of 7.22°in Damon group (P<0.05). U1-MxP in MBT and Damon were 110.61°and 114.11°. U1-MxP decreased 12.06°in MBT group, while significant change was deteced in Damon group of 7.61°(P<0.05). CONCLUSIONS: Application of Damon high torque appliances in extraction treatment of maxillary protrusion patients yielded better control of the labial crown torque of anterior teeth, and avoided excessive lingual inclination of anterior teeth compared with MBT in adduction of upper anterior teeth.

[Comparative evaluation of two kinds of micro-implant system with different size].

OBJECTIVE: To offer some reference for micro-implant's development and population by analyzing clinical application of two kinds of micro-implant systems. METHODS: 38 patients treated with MIA (micro-implant anchorage) and 28 patients treated with SDIA (self-driven titanium implant for orthodontic anchorage) were included. Analyzing the rate of lost implants, the gum's reactivity and the efficiency of moving teeth summarized the excellences and shortcomings of two systems. RESULTS: 1) Six of MIA implants fell off after being inserted. Seven of SDIA implants lost when they had been implanted for a month. But they were stable after being inserted again. 2) The gum around 12 SDIA implants got inflammation symptom, but the gum around MIA implants was normal. 3) Both MIA implants and SDIA implants could move teeth effectively and persistently when they were stable. CONCLUSION: When we apply micro-implant in clinic, we should prevent it from closing roots of teeth and choose the small tip micro-implant. The embedded position should be in area of attachment gum. At the same time, the areas around the tip of micro-implant should be keeping clean.

[Finite element analysis of mechanical characteristics during retracting mandibular incisors through sliding mechanics].

PURPOSE: To analyze the mechanical characteristic changes of teeth and arch under different loading direction during retracting mandibular incisors through implant, simulating clinical loading system. METHODS: Three- dimensional finite element model, including brackets, archwire, crampable hooks and implants, was reconstructed. The force direction was determined by connecting the points in crampable hook and the center point of implant, and the force point and force direction were changed with the adjustment of the height of crampable hook and the height of implant. Then three-dimensional movement trend of teeth, stress distribution in periodontal membrane and the largest displacement of archwire nodes in each group were calculated and analyzed. SPSS13.0 software package was used for statistical analysis. RESULTS: It was found that the height of implant and the height of crampable hook were correlated with the movement of teeth and stress distribution in periodontal membrane (P<0.01). The movement trend of teeth in the condition of different height of implant and different height of crampable hook was illustrated as follows:(1)with the height increase of crampable hook, the movement trend of the central and lateral incisors varied from mesial lingual tipping to mesial labial tipping. However, canines tipped distally and lingually; the second premolars tipped mesially and lingually, and the first molar roots tipped distally and buccally with decreasing tipping angle. (2) The largest stress distribution in the whole arch was located in the labial apical one-third area of the lateral incisors, while that of canines and the first molars was located in the alveolar ridges and root bifurcations. CONCLUSIONS: These findings indicate that the different movement trend during retracting anterior teeth can be achieved through the adjustment of the height of crampable hook, and implant, anchorage can effectively control anterior movement of the posterior teeth. Supported by Research Fund of Bureau of Science and Technology of Nantong City (Grant No. S40023).

[Comparison between J-hook and micro-implant anchorage in the treatment of patients with bimaxillary protrusion].

OBJECTIVE: To compare the difference between J-hook and micro-implant anchorage in the treatment of patient with bimaxillary protrusion. METHODS: Thirty patients with bimaxillary protrusion were divided into two groups (J-hook and micro-implant groups) and treated with MBT appliance. Four first premolars were extracted in all patients. Cephalometric analyses were carried out before and after treatment. RESULTS: In J-hook group and micro-implant group,computerized cephalometric analysis revealed that before treatment U6C-PP was (12.4 +/- 0.2) mm and (12.5 +/- 0.1) mm, respectively,and after treatment U6C-PP was (12.6 +/- 0.1) mm and (12.8 +/- 0.1) mm,respectively. The difference between J-hook group and microimplant group was significant (P < 0.01). The other differences of cephalometric analyses between J-hook group and micro-implant group was not significant. CONCLUSIONS: Both J-hook and micro-implant could provide adequate anchorage in the treatment of patients with bimaxillary protrusion.