Distinctive Craniofacial and Oral Anomalies in MN1 C-terminal Truncation Syndrome.

MN1 C-terminal truncation (MCTT) syndrome was first reported in 2020 and only 28 patients have been recorded to date. Since MCTT syndrome is a newly defined and rare syndrome with many clinical features, the present study reviewed the manifestations and management of oral and dental anomalies. Gene variants of MCTT syndrome and their positive phenotypes were summarised. The phenotypes of variants in two exons differed from each other mainly in the craniomaxillofacial region, including brain MRI abnormalities and palatal morphology. Pathogenic mechanisms, especially in craniofacial and oral anomalies, were discussed. Appropriate treatments in the stomatology and respiratory departments could improve the symptoms of MCTT syndrome. The different sites of MN1 gene variants may influence the clinical symptoms and there may be racial differences in MCTT syndrome. We recommend oral and pulmonary evaluations for the multidisciplinary treatment of MCTT syndrome.

[Three-dimensional assessment and study on temporomandibular joint and the maxillary characteristics of skeletal Class â ¢ mandibular deviation patients].

PURPOSE: To study the temporomandibular joint morphology and position and the maxillary characteristics of skeletal Class Ⅲ mandibular deviation patients with vertical disproportion in bilateral gonions. METHODS: Overall 79 adult patients with skeletal Class Ⅲ malocclusions were selected. Craniofacial spiral CT scanning was performed, and three-dimensional reconstruction of the temporomandibular joint(TMJ) was carried out by using ProPlan CMF3.0 three-dimensional analysis software. The patients were divided into two groups according to the deviation degree of the mentum: symmetric group (the S group: n=24) and deviation group (n=55). The deviation group was divided into two subgroups according to whether there was vertical disproportion in bilateral gonions, i.e., ASV group: there were vertical differences in bilateral gonions(n=27), and ASNV group: there was no vertical difference in bilateral gonions (n=28). Seven condylar morphological and position indicators and nine maxilla-related indicators were measured. SPSS 22.0 software package was used for statistical analysis. RESULTS: In deviation group, the condylar length on the deviated side was shorter than the opposite side, the difference value between the two sides was greater than the symmetric group, and there were asymmetry and different degrees of disproportion in the three-dimensional direction in the maxilla. In ASV group, the angle of the condylar axis to the horizontal plane on the deviated side was smaller and the anteroposterior diameter of the condyle was smaller. In ASV group, the mediolateral dimension of condyle on the deviated side were smaller. From variance analysis and multiple comparisons, the difference of condylar length on both sides in ASV group and ASNV group was greater than that in the symmetric group. There were asymmetries in the maxillae in ASV group and ASNV group, and the maxillary width on the deviated side was greater than that on non-deviated side. Transverse maxillary disproportion was more likely to occur in the ASNV group. The vertical maxillary disproportion on both sides in ASV group was larger than that in ASNV group and S group, and the deviated side was smaller than the opposite side. CONCLUSIONS: The TMJ morphology and position of skeletal Class Ⅲ mandibular deviation patients with vertical disproportion in bilateral gonions and the maxillary asymmetry in the three-dimensional direction require attention in the diagnosis and conceptual design of surgical-orthodontic treatment.

Identification of Hypoxia-Related Molecular Classification and Associated Gene Signature in Oral Squamous Cell Carcinoma.

The high heterogeneity of oral squamous cell carcinoma (OSCC) is the main obstacle for individualized treatment. Recognizing the characteristics of different subtypes and investigating the promising strategies for each subclass are of great significance in precise treatment. In this study, we systematically evaluated hypoxia-mediated patterns together with immune characteristics of 309 OSCC patients in the TCGA training set and 97 patients in the GSE41613 testing set. We further identified two different hypoxia subtypes with distinct immune microenvironment traits and provided treatment programs for the two subclasses. In order to assess hypoxia level individually, we finally constructed a hypoxia-related risk score, which could predict the clinical outcome and immunotherapy response of OSCC patients. In summary, the recognition of different hypoxia patterns and the establishment of hypoxia-related risk score might enhance our understanding of the tumor microenvironment of OSCC and provide more personalized treatment strategies in the future.

[Correlation between social psychology and personality characteristics and treatment options for adult patients with skeletal malocclusion].

OBJECTIVE: This study aims to explore factors affecting the dental aesthetic social psychology of patients with skeletal malocclusion and to measure the relationship between the objective orthodontic requirements and the subjective treatment requirements of patients. This work provides a reference for doctors to measure patients' orthodontic treatment needs. METHODS: Adult patients with skeletal malocclusion were chosen as the research object. Questionnaire survey was used to analyze factors influencing the psychosocial impact of dental aesthetics questionnaire (PIDAQ), index of orthodontic treatment need (IOTN), and Eysenck personality questionnaire-revised short scale for Chinese (EPQ-RSC). The relationship among PIDAQ, IOTN, EPQ-RSC, and treatment options was also evaluated. RESULTS: Seventy-two valid questionnaires were collected from adult patients with skeletal malocclusion. 1) The PIDAQ scores significantly differed among different occupations (P<0.05) but were not affected by other general conditions such as gender and age. 2) Patients of different dental health component (DHC) grade and ages had different AC self-assessment scores (P<0.01, P<0.05). The AC self-assessment score was positively correlated with the PIDAQ score (P<0.05). 3) Males accounted for a higher proportion of patients who received treatment. Younger patients (18-28 years old) were more likely to receive treat-ment when their own dental aesthetics were poor. People with the higher monthly expenditure accounted for the larger proportion of surgical patients. 4) The PIDAQ score had no significant effects on the choice of opera-tion (P>0.05). People with low educational level were more likely to receive surgery if their psychosocial impacts of dental aes-thetics were serious. 5) The score of psychoticism scale of EPQ-RSC and the educa-tional level had a mutual influence on the PIDAQ score (P<0.01). Moreover, the neuroticism scale and AC self-assessment scores had a mutual influence on the PIDAQ score (P<0.05). However, this study did not find a correlation between personality traits and treatment options. CONCLUSIONS: Many factors, such as personal natural conditions, subjective aesthetic evaluation of teeth, and psychosocial impacts of dental aesthetics, affect patients' treatment options. Personality characteristics can play a certain role in dental aesthetics social psychology.

[Meta-analysis of the condylar position with mandibular deviation].

PURPOSE: This study was aimed to analyze the differences of condylar position between the mandibular deviation and the individual normal occlusion. METHODS: Databases of PubMed,Embase,CNKI ,Wanfang ,VIP and CBL were searched for the relevant articles about condylar position with mandibular deviation. The deadline was June 2017.Data quality evaluation and extraction were independently conducted by two authors. Then meta analysis was performed using Rev Man 5.3 software. RESULTS: Six articles on controlled study of the condylar position in patients with mandibular deviation and individuals with normal occlusion were included. 122 patients had mandibular deviation and 110 had normal occlusion. Meta analysis results showed that the condylar superior space[MD=-0.38,95%CI(-0.74,-0.01),P=0.04]and anterior space[MD=-0.72,95%CI(-0.99,-0.04),P＜0.00001]of the deviation side in mandibular deviation group were significantly greater than that of the opposite side; The condylar posterior space[MD=-0.35,95%CI(0.25,0.45),P＜0.00001]of the deviation side in mandibular deviation group was significantly smaller than that of the opposite side. The condylar posterior space of deviation side[MD=-0.58,95%CI(-0.88,-0.28),P=0.0002],opposite side[MD=-0.30,95%CI(-0.59,-0.00),P=0.05] and the anterior space of opposite side[MD=-0.85,95%CI(-1.58,-0.13),P=0.02] in the mandibular deviation group was significantly smaller than that in the individuals with normal occlusion; the differences were statistically significant. There was no significant difference in the condylar superior space between the deviation side[MD=-0.56,95%CI(-1.14,0.02),P=0.06] and the opposite side[MD=-0.58,95%CI(-1.27,0.10),P=0.10] and the anterior space[MD=-0.05,95%CI(-0.35,0.46),P=0.80]in deviation side in the mandibular deviation group ,comparing with individuals with normal occlusion. CONCLUSIONS: The condylar position of deviation side in patients with mandibular deviation is posterior and inferior, comparing with the opposite side. The condylar position of deviation side in patients with mandibular deviation is posterior, comparing with the individuals with normal occlusion.

[The relationship between labial-lingual inclination and the thickness of the alveolar bone in the mandibular central incisors assessed with cone-beam computed tomography].

PURPOSE: To investigate the alveolar bone thickness of mandibular central incisors with different labial-lingual inclinations by cone-beam computed tomography (CBCT). METHODS: CBCT and lateral cephalometric images of 60 patients were chosen. The data was respectively classified into 3 groups by L1-MP: lingual inclination group (L1-MP<85.6°); normal group (L1-MP 85.6°-99.6°), and labial inclination group(L1-MP>99.6°). Three-dimensional reconstruction was made for CBCT, and the sagittal images of the largest alveolar bone area along the tooth axis were chosen. The central incisor roots were divided into 4 sections from cementoenamel junction to root apex, then the labial and lingual alveolar bone thickness were measured and added up to get total alveolar bone thickness, and the occurrence of fenestration and dehiscence were recorded. The data was analyzed with SPSS 17.0 software package. RESULTS: The alveolar bone thickness on lingual side and the total bone thickness were significantly different between every 2 sections of all the measured zone. The average values of bone thickness on labial side were thinner than that on lingual side in sections of middle 1/2, root apex 1/4 and root apex. The total bone and lingual bone were thinner in lingual inclination group than in labial inclination group at root apex, root apex 1/4 and middle 1/2. Labial and lingual inclination group were more likely to develop dehiscence (P<0.05). CONCLUSIONS: Lingual and total alveolar bone of central incisors become increasingly thinner from root apex area to cementoenamel junction. The total bone and lingual bone are thinner in lingual inclination group than in labial inclination group. Labial or lingual inclined incisors have higher incidence of dehiscence.

[The relationship between maxillary anterior impacted teeth and sagittal facial type].

PURPOSE: To investigate the relationship between impaction of maxillary anterior teeth and sagittal facial type and evaluate the dentofacial morphological characteristics of patients with maxillary teeth impaction. METHODS: Totally 90 patients with maxillary anterior teeth impaction were divided into 3 groups (one incisor impaction, one canine impaction and two canines impaction), and their cephalometric films were measured and analyzed. They were further divided into Class I, II and III facial types according to ANB and the constituent ratio were calculated. SPSS 17.0 software package was applied for Student's t test and chi-square test. RESULTS: SNA, A'-Ptm' and L1-NB were smaller than the normal value in the 3 groups. Convexity, L1-MP, ANB and Wits appraisal were smaller while AB plane angle, U1-NA and U1-NA were greater than the normal value in groups of one and two canines impaction; S'-Ptm', L1-NB were smaller while U1-L1 was greater than normal value in group of two canines impaction; Among the 3 groups, ANB and Wits appraisal were the smallest while AB plane angle was the greatest in group of two canines impaction. The sagittal facial type of 90 patients was mainly Class I (50%), but Class III in group of two canines impaction increased to 40%. CONCLUSIONS: Impacted maxillary anterior teeth might result in short maxillary basal bone. One canine impaction has the greatest influence than one incisor impaction on sagittal position of jaws. Two canines impaction has the greatest impact on sagittal facial type and tends to be Class III facial type.

[Effect of rapamycin combined with cisplatin on head and neck squamous cancer cells regulated by CCL19].

OBJECTIVE: To investigate the synergistic effects of rapamycin and cisplatin on head and neck squamous cancer cells regulated by chemokine (C-C motif) ligand 19 (CCL19). METHODS: The role of rapamycin and cisplatin was detected on cell-cycle and apoptosis in CCL19 induced PCI-4B and PCI-37B cells by methyl thiazolyl tetrazolium (MTT) and flow cytometry (FCM). Dose-effect relationship parameters and combination index (CI) were calculated on the median-effect equation and multiple drug effect equation using computer software CalcuSyn. Statistical analysis was performed by the unpaired student's t-test. RESULTS: Rapamycin and cisplatin could respectively increase the growth arrest, the proportion of G(1) phase and apoptosis of CCL19 induced cancer cells (P < 0.05). Under inhibitory concentration 50% (IC(50)), CI was less than 1, and in IC(75), it was more than 1 in PCI-4B cells. In PCI-37B cells, under IC(75), CI was less than 1, and in IC(90), it was more than 1. CONCLUSIONS: Rapamycin and cisplatin can inhibit CCL19-regulated PCI-4B and PCI-37B cells' survival. The two drugs have synergistic effects when used in combination.

NF-κB participates in chemokine receptor 7-mediated cell survival in metastatic squamous cell carcinoma of the head and neck.

Metastatic squamous cell carcinoma of the head and neck (SCCHN) has been shown to express chemokine receptor 7 (CCR7), which activates phosphoinositide-3 kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) signal pathway to promote the invasion and survival of SCCHN cells. Since nuclear factor-kappa B (NF-κB) is shown to be the downstream signal molecule of PI3K/Akt in many tumors, we investigated whether it also exists in the CCR7 pathway in SCCHN, and the relationship between NF-κB and PI3K/Akt/mTOR, and the role it plays in SCCHN. We assayed the phosphorylation of the inhibitor of NF-κB (IκBα), the NF-κB DNA-binding capacity and location. The results showed that the interaction between CCR7 and the ligand for CCR7, CCL19, induces phosphorylation of IκBα, causes NF-κB to translocate to the nucleus and raises the DNA-binding capacity of NF-κB. The phosphorylation and DNA-binding capacity were abolished by the inhibition of CCR7, PI3K, Akt and mTOR. Further research demonstrated that inhibitors of NF-κB and CCR7-PI3K attenuate the survival of CCR7-mediated cells, causing decreased viability, increased apoptosis and increased cell cycle arrest in SCCHN cells. In clinical samples from 78 patients, immunohistochemical assay also showed that CCR7 and NF-κB are not only highly expressed in SCCHN, but also correlated with each other, and related to lymph node metastasis and clinical stage. Together, our data indicate that NF-κB is activated by CCR7 via PI3K/Akt/mTOR, and this signal pathway plays an important role in regulating the cell survival and prognosis of SCCHN.

CCL19-induced chemokine receptor 7 activates the phosphoinositide-3 kinase-mediated invasive pathway through Cdc42 in metastatic squamous cell carcinoma of the head and neck.

Metastatic squamous cell carcinoma of the head and neck (SCCHN) has been shown to express chemokine receptor 7 (CCR7), which activates phosphoinositide-3 kinase (PI3K) to promote invasion and survival of SCCHN cells. We hypothesized that Cdc42 might be involved in the CCR7-PI3K pathway. Adhesion assays, migration assays, immunofluorescence staining, Western blotting and immunohistochemical analysis were used to find whether Cdc42 can be activated by CCL19 (the CCR7 ligand) and its role in SCCHN. Results showed that CCL19 induced polarized localization of Cdc42 and actin polymerization in the leading edge of migrating cells. The level of activated membrane-bound Cdc42 was elevated, as measured by the GTPase activity pull-down assay. The increased membrane localization and membrane-bound activity of Cdc42 were abolished by CCR7 and PI3K inhibition, indicating the involvement of Cdc42 in the CCR7-PI3K cascade. Knockdown of Cdc42 by small interfering RNA (siRNA) led to significant reduction in the activation of Rac, filamentous actin (F-actin) accumulation as well as in the migration and invasion induced by CCL19. Taken together, our data indicate the important role played by Cdc42 in CCL19-induced migration and invasion of SCCHN cells.

The chemokine receptor 7 regulates cell adhesion and migration via beta1 integrin in metastatic squamous cell carcinoma of the head and neck.

Migration and adhesion of tumor cells are essential prerequisites for the formation of metastases in malignant diseases. Chemokine receptor 7 (CCR7) has been shown to regulate integrin which can then facilitate adhesion of cancer cells to and/or migration through the extracellular matrix (ECM). In order to identify the connection between CCR7 and beta1 integrin, and the influence on cell adhesion and migration in metastatic squamous cell carcinoma of the head and neck (SCCHN). We use adhesion assays, migration assay, immunofluorescence staining, western blotting, and immunohistochemical analysis to find whether beta1 integrin can be activated by CCL19 (CCR7's ligand) and its role in SCCHN. The experiments were performed in the metastatic SCCHN cell line PCI-37B after pre-incubation of the cells with CCL19 and beta1 integrin inhibitors RGD-peptide. Our results demonstrate that CCR7 favours PCI-37B cell adhesion and migration, and induces reorganization of the actin cytoskeleton and up-expression of beta1 integrin protein. beta1 integrin inhibitor RGD-peptide can block all these effects. Taken together, our data indicate that CCR7 regulate cell adhesion and migration via beta1 integrin in metastatic SCCHN, and these results can provide a basis for new strategies in preventing metastases of SCCHN.

[The effect of CCL19 on the viability of head and neck squamous cancer cells].

PURPOSE: To study the role of CCL19 on the viability,cell-cycle and apoptosis of head and neck squamous cancer cells. METHODS: We assayed the growth arrest induced by cisplatin in 4A cells and 4B cells by MTT, detected the role of CCL19 on the effect of cisplatin and observed the change of morphology by transmission electron microscope, evaluated cell-cycle and apoptosis of 4B cell pretreated by CCL19 and cisplatin via FCM. Statistical differences between the two groups were evaluated using the unpaired Student's t test. All statistical analyses were performed with SPSS 11.0 software package. RESULTS: The growth arrest of 4B cell by cisplatin was significantly higher than 4A(P<0.05). CCL19 could protect 4B cell against inhibition, but no effect on 4A. CCL19 contributed to 4B by promoting to normal morphology, reducing G1 phase arrest, inhibiting apoptosis. CONCLUSIONS: Cisplatin works better in 4B cell than in 4A cell, and CCL19 can inhibit its effect, which provide a new way to treat head and neck squamous cancer. Supported by National Natural Science Foundation of China (Grant No.30672331) and Foundation of Liaoning Provincial Educational Commission (Grant No.2009A755).

Mammalian target of rapamycin (mTOR) is involved in the survival of cells mediated by chemokine receptor 7 through PI3K/Akt in metastatic squamous cell carcinoma of the head and neck.

Metastatic squamous cell carcinoma (SCC) of the head and neck expresses chemokine receptor 7 (CCR7), which activates phosphoinositide-3 kinase (PI3K) to promote invasion and survival of SCC cells in the head and neck. We hypothesised that mammalian target of rapamycin (mTOR) may be the downstream molecule of the CCR7-PI3K pathway. Results have shown that interaction between CCR7 and its ligand CCL19 induces the phosphorylation of mTOR and its target p70s6k. This phosphorylation is abolished by inhibition of CCR7 and PI3K/Akt, indicating that mTOR is involved in the CCR7-PI3K cascade. The inhibitors of mTOR and CCR7-PI3K also lead to a significant increase in CCL19-induced death, apoptosis, and cell-cycle arrest of metastatic SCC cells in the head and neck. Taken together, our data indicate the important part played by mTOR in CCR7-induced survival of such SCC cells.

[Effect of HA/TiO2 coating titanium surface on the growth of MG63].

PURPOSE: To evaluate the bioactivity of titanium surface treated by micro-arc oxidation (MAO) combined with ion beam assisted deposition (IBAD). METHODS: Titanium surfaces were treated by machined(S0), micro-arc oxidation(S1) and micro-arc oxidation combined with IBAD(S2), respectively. The topography and roughness of surfaces were determined by profilometer, and the bioactivity of the surface was evaluated by CLSM, MTT assay and ALP activity of cells. The data was analyzed by one-way ANOVA using SPSS11.0 software. RESULTS: The surfaces of S2 group were smoother than those of S1 group. On day 5, the OD value of S2 group was the highest among the three groups.10 days later, ALP activity on S1 and S2 groups were higher than that of S0 group. CONCLUSIONS: It is concluded that IBAD technique which provides HA coating on MAO surface could reinforce the bioactivity of micro-arc oxidation and could have a rapid osseointegration.

[Effect of chemokine receptor 7 small interfering RNA on proliferation and invasion of squamous cell carcinoma of head and neck].

OBJECTIVE: To study the effect of chemokine receptor 7 (CCR-7) small interfering RNA (siRNA) on proliferation and invasion of squamous cell carcinoma of head and neck (SCCHN). METHODS: CCR-7 siRNA was co-transfected into SCCHN cell line PCI-4B using Lipofectamine 2000. CCR-7 protein level was detected by western blotting. SCCHN cell proliferation was detected by MTT, and the change of actin cytoskeleton observed by confocal laser scanning microscope. Transwell assays were used to determine chemotaxis and invasion of SCCHN cells. The activity and nuclear translocation of nuclear factor-kappa B (NF-kappa B) were detected by TransAM NF-kappa B p65 kit and fluorescence microscope respectively. RESULTS: After CCR-7 siRNA transfection, the protein level of CCR-7 was significantly decreased. The changes induced by CCL-19, including increased proliferation rate, polarized actin polymerization, increased chemotaxis rate and invasion rate, were all abolished by CCR-7 siRNA transfection. CCR-7 siRNA also diminished CCL-19-induced NF-kappaB activation and nuclear translocation. CONCLUSIONS: CCR-7 siRNA could inhibit expression of CCR-7 and diminish the increased proliferation and invasion of SCCHN induced by CCL-19 in vitro. CCR-7 siRNA may provide a potential treatment strategy for SCCHN.

[Changes of interlukin-1beta and tumor necrosis factor-alpha levels in gingival crevicular fluid during orthodontic tooth movement].

OBJECTIVE: To investigate the dynamic changes of interlukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) in gingival crevicular fluid (GCF) during orthodontic tooth movement, and to discuss the biological significance. METHODS: Fifteen patients were chosen as subjects. For each patient, upper and lower canines at one side having one treatment for distal movement by elastic chain served as the experimental teeth, whereas the contralateral ones were used as controls. The GCF were taken before activation and at 1, 24, 48, 72, 168 hours respectively after initiation of the experiment. The levels of IL-1beta and TNF-alpha in GCF were determined by radioimmunoassay. RESULTS: The levels of IL-1beta and TNF-alpha in experimental group began to increase at 24 hours and reached to its peak value at 72 hours after initiation of the experiment, but their levels returned to baseline at 168 hours. Both of them, however, remained at the baseline level in control group. The changes of the two cytokines level were found statistically significant at 48 and 72 hours (P<0.05) between experimental and control group. No statistically significant were observed before activation and at 1, 168 hours after application of orthodontic forces (P>0.05) between experimental and control group. CONCLUSION: The levels of IL-1beta and TNF-alpha in gingival crevicular fluid experience dynamic changes during the early phase of orthodontic treatment, indicate that they might play an important role in the process of alveolar regeneration and tooth movement.

[Study on the characteristics and reasons for mistakes in some orthodontic cases].

PURPOSE: To evaluate the characteristics and reasons for mistakes in some orthodontic cases. METHODS: 37 cases after or during treatment in other hospitals with mis-treatment were chosen, their original records as well as the records when they came to our hospital were collected, their original and present malocclusions were classified and the characteristics and reason of mistakes were analysed. RESULTS: Among the 37 cases, 26 cases had class-III malocclusion which account for 70.27% of the group, especially for the malocclusions began in mixed dentition and the problems developed from anterior dental crossbite to severe skeletal crossbite with dentofacial asymmetry and openbite. The main reasons lie in the mistakes of diagnosis and treatment planning, preventive treatment,appliance fabrication,use of extraoral arch and elastics, treatment processes, et al. CONCLUSIONS: There are various characteristics and reasons of treatment mistakes, but the problems lie mainly in class-III malocclusion especially during mixed dentition which indicates that we should pay more attention to the treatment of class-III malocclusion.