Single-cell Transcriptomics Reveals Activation of Macrophages in All-trans Retinoic Acid (atRA)-induced Cleft Palate.

Cleft palate is among the most common birth defects with an impact on swallowing and speaking and is difficult to diagnose with ultrasound during pregnancy. In this study, we systematically capture the cellular composition of all-trans retinoic acid (atRA)-exposed and normal embryonic gestation 16.5 days mouse palate by the single-cell RNA sequencing technique. The authors identified 14 major cell types with the largest proportion of fibroblasts. The proportion of myeloid cells in atRA-exposed palate was markedly higher than those in the normal palate tissue, especially M1-like macrophages and monocytes. The upregulated genes of the different expression genes between atRA-exposed palate and normal palate tissue were linked to the biological processes of leukocyte chemotaxis and migration. Protein TLR2, CXCR4, THBS1, MRC1, transcription factor encoding genes Cebpb, Fos, Jun, Rela, and signaling pathway IL-17 and phagosome were found to be significantly involved in these processes. Subsequently, cellular communication network analysis suggested that myeloid-centered cell interactions SELL, SELPLG, MIF, CXCL, ANNEXIN, THBS, and NECTIN were significantly more activated in atRA-exposed palate. Overall, we delineate the single-cell landscape of atRA-induced cleft palate, revealing the effects of overexposure to atRA during palate tissue development and providing insights for the diagnosis of cleft palate.

Three-dimensional Measurement of the Zygomatic-maxillary Complex in the Class III Malocclusion Patients with Maxillary Retrusion.

This study investigated the anatomic features of the zygomatic-maxillary complex in patients with maxillary retrusion without clefts. Individuals were grouped, and craniofacial measurements were performed for 21 individuals with skeletal Class III malocclusion with maxillary retrusion (CIII) and 48 individuals from the control group (CG). We evaluated the predetermined hard-tissue and soft-tissue points of the facial profile in each group. Independent sample t -tests were performed to determine the differences between groups (significance set at P <0.05). Multiple points on the midface, including the most posterior point on the contour of the maxillary alveolar process, lowest point of the zygomaticomaxillary suture, furthest point to the zygomatic self-base plane, superior point in the infraorbital foramen, and lowest point of the inferior margin of the orbit to the coronal plane were smaller in CIII than in CG (all P <0.05). The soft tissue thickness in these regions was significantly increased compared with that in the normal group. In summary, for class III malocclusion patients with maxillary retrusion, the deficiency in the midface gradually decreased going upward, with the deficiency at the maxillary alveolar level being the most serious. To some extent, soft tissues compensate for the deficiencies in the facial skeleton, and standard Le Fort I osteotomy advancement was sufficient to achieve a harmonious appearance.

Hiker, a new family of DNA transposons encoding transposases with DD35E motifs, displays a distinct phylogenetic relationship with most known DNA transposon families of IS630-Tc1-mariner (ITm).

DNA transposons play a crucial role in determining the size and structure of eukaryotic genomes. In this study, a new family of IS630-Tc1-mariner (ITm) DNA transposons, named Hiker (HK), was identified. HK is characterized by a DD35E catalytic domain and is distinct from all previously known families of the ITm group. Phylogenetic analyses showed that DD35E/Hiker forms a monophyletic clade with DD34E/Gambol, indicating that they may represent a separate superfamily of ITm. A total of 178 Hiker species were identified, with 170 found mainly in Actinopterygii, one in Chondrichthyes, six in Anura and one in Mollusca. Gambol (GM), on the other hand, are found in invertebrates, with 18 in Arthropoda and one in Platyhelminthes. Hiker transposons have a total length ranging from 2.14 to 3.67 kb and contain a single open reading frame that encodes a protein of approximately 370 amino acids (range 311-413 aa). They are flanked by short terminal inverted repeats (TIRs) of 16-30 base pairs and two base pair (TA) target-site duplications. In contrast, most transposons of the Gambol family have a total length of 1.35-5.96 kb, encode a transposase protein of approximately 350 amino acids (range 306-374 aa), and are flanked by TIRs that range from 32 to 1097 bp in length. Both Hiker and Gambol transposases have several conserved motifs, including helix-turn-helix (HTH) motifs and a DDE domain. Our study observed multiple amplification waves and repeated horizontal transfer (HT) events of HK transposons in vertebrate genomes, indicating their role in diversifying and shaping the genomes of Actinopterygii, Chondrichthyes, and Anura. Conversely, GM transposons showed few Horizontal transfer events. According to cell-based transposition assays, most HK transposons are likely inactive due to the truncated DNA binding domains of their transposases. We present an updated classification of the ITm group based on these findings, which will enhance the understanding of both the evolution of ITm transposons and that of their hosts.

A 3-Dimensional Measurements of Bone and Airway Variables After Le Fort I Distraction Osteogenesis in Patients With Cleft Lip and/or Palate-Induced Midface Hypoplasia: A Retrospective Study.

The authors retrospectively analyzed the effects of Le Fort I advancement with distraction osteogenesis on skeletal and airway variables in patients with midfacial hypoplasia induced by cleft lip and/or palate using 3-dimensional computed tomography reconstructions. The authors enrolled 23 subjects with moderate-to-severe midface hypoplasia induced by cleft lip and palate who were treated with Le Fort I distraction osteogenesis (mean age, 19.22±3.48 y; male/female ratio, 20/3); computed tomography images (1 before distraction and another at completion of distraction) were acquired. A 3-dimensional craniometric findings and airway volumes for the nasal cavity, nasopharynx, velopharynx, and upper and lower oropharynx were compared before and after distraction. The relationships between craniofacial morphology and changes in airway volume were also assessed ( P <0.05 was considered significant). Significant increases were observed in airway volumes for the nasal cavity (13.85%), nasopharynx (50.82%), velopharynx (29.57%), and upper oropharynx (36.92%) ( P =0.007, P <0.001, P =0.023, and P <0.001, respectively), whereas no significant changes were observed for the lower oropharynx ( P =0.117). Maxillary horizontal advancement was positively correlated with the airway volumes of the nasopharynx and upper oropharynx after distraction osteogenesis ( rs =+0.451, P =0.031; rs =+0.548, P =0.007); however, no significant correlations were observed for the nasal cavity and velopharynx. The authors' finding indicate that despite rotation of the mandible along with the maxilla, this change does not impact airway volume at the mandibular level. Le Fort I distraction osteogenesis can be feasible for patients with cleft lip and palate-induced midface hypoplasia, with satisfactory appearance and occlusion. Long-term detailed follow-up of the patients postdistraction osteogenesis is warranted.

Observation of Nasal Morphology in Unilateral Microform Cleft Lip Repaired by a Hidden Skin Incision.

BACKGROUND: Microform cleft lip is the mildest type of cleft lip without obvious defects of the upper lip. The nose deformities of microform cleft lip include flattened nostril rim, alar base asymmetry, and septal deviation. A hidden skin incision with nasal base muscle reconstruction was introduced in nose deformities of microform cleft lip. METHOD: To investigate the operative effect, we reviewed 21 patients with microform cleft lip treated with a hidden skin incision with nasal base muscle reconstruction from May 2020 to October 2022. Photogrammetric nasal morphometric measurements were compared preoperatively and six months postoperatively. The proportional value was obtained from the cleft and the noncleft sides, and paired t-test analysis was used to evaluate the surgical outcome. RESULT: Significant differences were found in all nasal morphologic measurements at 6 months postoperatively compared to preoperatively (p < 0.05). After surgery, the alar base and nostril were narrowed, while the lateral lip height was increased on the affected side. The height of the nostrils on the affected side was increased, and the nasal columella deviation was released. In addition, the ratio of the cleft-to-noncleft nostril area was closer to 1.0 after surgery. CONCLUSION: The unilateral microform cleft lip nasal deformity can be repaired through a small hidden incision. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Three-Dimensional Evaluation of Deformed Noses in Patients With Unilateral Cleft Lip and Palate: A Meta-Analysis.

ABSTRACT: Multiple surgeries for patients with cleft lip and palate may be required to repair secondary deformities after the completion of cleft repair. This meta-analysis aimed to evaluate the three-dimensional nasal morphology in patients with unilateral cleft palate who underwent cleft lip and palate repair but did not undergo terminal nasal repair. PubMed, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang Data, and SINOMED databases were searched from inception until December 2020. Studies involving patients ages ≥6 years with cleft lip and palate who did not undergo terminal nasal repair were included. Quantitative data were obtained through three-dimensional evaluation. Mean weighted effect sizes with 95% confidence intervals, heterogeneities, and publication biases were assessed using raw data obtained from 13 studies. In general, patients with unilateral cleft lip and palate had a significantly wider nose; shorter bridge length and nasal height; larger forehead-nose angle, nasal tip angle, and alar slope angle; and smaller nasolabial angle. The number of studies that included patients with unilateral cleft lip, unilateral cleft lip and alveolus, and unclassified deformities was limited, and their results were similar to those involving patients with unilateral cleft lip and palate. Patients with unilateral cleft tend to have short, flat, and wide noses. Nasal tip elevation and alar base adduction should be prioritized during terminal nasal repair to achieve more normalized cleft-side nostrils.

Three-Dimensional Computed Tomography Reconstruction and Measurement of Nasal End Deformity in Complete Unilateral Cleft Lip and Palate.

BACKGROUND: The repair of nasal deformities secondary to cleft lip and palate is complex and requires reliable preoperative nasal 3-dimensional assessment. This study explored nasal end (defined as the lower third of the external nasal and vestibular parts of the nasal cavity) deformities secondary to unilateral complete cleft lip and palate. METHODS: Three-dimensional nasal end morphometric measurements were obtained from 48 patients who had undergone Millard cleft lip repair and reached skeletal maturity (cleft group) and from 36 age- and ethnicity-matched normal subjects (control group). For the cleft group, paired t tests and 1-way analysis of covariance were used to evaluate the internal and external morphological characteristics of the cleft and noncleft sides of the nasal end, and correlation analysis was done to evaluate the relationship between cleft-side measurements. RESULTS: In the cleft group, the cleft side showed significantly smaller nasal vestibular volume and skin area, nostril area, nasal column length, and nostril height and greater nostril base length and nasal alar length than the noncleft side (all P < 0.05). Controlling for sex, there were significant differences in the nasal vestibular volume and skin area, internal nasal valve area, long nostril diameter, nostril base length, columella length, nostril height, and nasal alar length between the cleft and control groups (all P < 0.05). On the cleft side, the area of the skin lining of the nasal vestibule positively correlated with the alar length (r = 0.67, P < 0.05). CONCLUSIONS: Three-dimensional nasal end reconstruction provides a more detailed preoperative nasal end morphological evaluation than previously available techniques. LEVEL OF EVIDENCE: Level III, case-control study.

Surgical Planning for Cleft Lip and/or Palate-Induced Moderate-to-Severe Midfacial Hypoplasia.

BACKGROUND: Distraction osteogenesis and conventional bimaxillary orthognathic surgery have been performed for the treatment of midfacial hypoplasia for a long time. However, the effect of these 2 techniques on the maxilla, mandible, and whole-facial profile is significantly different. In this study, we aimed to measure the pre- to post-treatment changes in maxillary prominence, mandible size, and facial length and compare them between these 2 techniques to inform selection of the best technique. METHODS: This single-center, retrospective study included 35 patients with a cleft lip and/or palate-induced midfacial hypoplasia; 25 were treated using rigid external distraction osteogenesis and 10 using bimaxillary orthognathic surgery. Three-dimensional measures of changes in facial structure were obtained from reconstructed computed tomography images and used to compare the effects of the 2 techniques. RESULTS: Satisfactory appearance and occlusion were achieved in all patients. Three-dimensional reconstruction of the craniofacial skeleton revealed significant maxillary advancement (P < 0.001), mandibular (clockwise) rotation (P < 0.001), and increased facial length (P < 0.001) after rigid external distraction osteogenesis and obvious shortening of the mandibular body (P < 0.001) after bimaxillary orthognathic surgery. CONCLUSION: Distraction osteogenesis can be selected as the first choice of treatment for cleft lip and/or palate-induced midfacial hypoplasia. A mandibular setback procedure can be performed as a second-stage surgery when severe temporomandibular joint complications develop with distraction osteogenesis. Bimaxillary orthognathic surgery results in an obvious shortening of the mandibular body, which is not a natural change in facial morphology. LEVEL OF EVIDENCE: Therapeutic III.

Temporomandibular joint dislocation in patients with cleft lip and palate after maxillary distraction osteogenesis: Three case reports.

INTRODUCTION: Distraction osteogenesis (DO) is a widely used for cleft and palate related maxillary hypoplasia. There has been little research on temporomandibular joint (TMJ) dislocation after maxillary DO. We present these 3 cases and analyze the possible causes for reference by other clinicians. PATIENT CONCERNS: In the late stages of maxillary DO, the patients gradually felt a decrease in mandibular mobility and suffered from limited mouth opening. Case 2 and 3 could open their mouth up to 1 and 2 fingers and Case 1 barely able to open her mouth at the completion of distraction. DIAGNOSIS: Case 1 and Case 3 were diagnosed as right TMJ dislocation and Case 2 had a TMJ dislocation on her left side. INTERVENTIONS: Patients with TMJ dislocation were repositioned with manipulation as soon as detected. OUTCOMES: There was no recurrence in all three cases during the postoperative follow-up period. CONCLUSIONS: Maxillary DO can sufficiently advance the maxilla in cleft lip and palate patients. Clinicians should be mindful of the TMJ dislocations that maxillary DO can exert on patients.

Hidden Blade Scalpel: A Useful Tool for the Treatment of Axillary Osmidrosis.

BACKGROUND: Axillary osmidrosis is a distressing problem that can particularly affect a patient's social life. In severe cases, patients may seek a surgical treatment to achieve a permanent effect. Many treatment techniques involving destruction or removal of the apocrine and eccrine glands have been developed. However, previous treatments have been hindered by surgical or aesthetic concerns. The purpose of this study was to evaluate the effect of the hidden blade scalpel procedure in treating axillary osmidrosis. METHODS: From December 2012 to December 2016, 372 patients with axillary osmidrosis underwent the hidden blade scalpel procedure. One 5-mm incision was made at approximately 1 cm beyond the axillary hairline. A hidden blade scalpel was then used to remove the subcutaneous tissue, including the plexus, apocrine and eccrine glands, and hair follicles, from the skin. The clinical efficacy was evaluated using a questionnaire. RESULTS: The hidden blade scalpel procedure resulted in a high percentage of patient satisfaction, a much shorter recovery time, and a low complication rate. CONCLUSION: The hidden blade scalpel procedure is an effective method for the treatment of axillary osmidrosis.