p38MAPK silencing attenuates scar proliferation after cleft palate repair surgery in rats via MRTF-A/SRF pathway.

Scarring is the primary factor of maxilla growth restriction among people who have undergone cleft palate repair surgery. p38 mitogen-activated protein kinase (p38MAPK) promotes fibrosis in a variety of organs. However, its role in post-surgery scarring on the hard palate has not been fully understood. This study is designed to investigate the role of p38MAPK in scar formation and maxilla growth of rats. We removed the mucosa on the hard palate of rats and applied the p38MAPK silencing adenovirus vector on it two weeks after surgery. Then the scarring tissue and maxilla growth were evaluated by histological and morphological examination. The effect of p38MAPK silencing on scarring-related genes in fibroblasts was also studied. We found that local injection of Ad-p38MAPK-1 in vivo effectively reduces the expression of p38MAPK and scarring-related proteins and weakens the impact of scarring on the width of the hard palate. Mechanistically, p38MAPK silencing inhibits the expression of α-smooth muscle actin (α-SMA) via mediating the production and nuclear localization of myocardin-related transcription factor A (MRTF-A) in fibroblasts. These results reveal a molecular pathway of scar formation involving p38MAPK/MRTF-A stimulation and support targeting p38MAPK as a potentially effective treatment for post-surgery scarring on the hard palate.

Virtual Surgical Planning and Three-Dimensional Printing to Aid the Anatomical Reduction of an Old Malunited Fracture of the Mandible.

ABSTRACT: Mandible fracture is a common injury in maxillofacial surgery. It causes not only maxillofacial dysfunction but also facial deformities. Malunited fractures of the mandible have been a vast challenge in clinical treatment due to the misalignment of the broken ends and the occurrence of occlusal disorders. This case report describes using virtual surgical planning and three-dimensional printing to treat a patient with malunited fracture of the mandible. Failing to perform mandibular surgery due to severe brain trauma after the car accident, the patient got malunited healing of mandible. The authors applied virtual surgical planning to perform preoperative analysis and surgical design on this patient, three-dimensional printing to fabricate occlusal plate, and models of the preoperative and postoperative mandible to guide the operation. Finally, the authors achieved the reduction and reconstruction of the mandible with satisfactory clinical results.

Negative pressure drainage-assisted irrigation for maxillofacial space infection.

OBJECTIVE: In this study, the clinical effect of negative pressure drainage-assisted irrigation (NPDI) technique was evaluated in treating maxillofacial space infection (MSI) by comparing with traditional technique. METHOD: A prospective study was conducted in 58 patients with MSI. The patients were randomly divided into two groups based on different treatment techniques. Thirty patients receiving NPDI were included in NPDI group, and 28 patients receiving traditional technique were included in traditional group. Case data (gender, age, etiology, concurrent illness, diabetes, involved spaces, preoperative white cell count, airway control method) and clinical effect (postoperative hospital stay, total cost of admission) for the two groups were analyzed. RESULTS: Patients in both groups were cured clinically. There were no significant differences in gender, age, etiology, concurrent illness, diabetes, involved spaces, preoperative white cell count, and airway control method in NPDI group and traditional group (p > .05). The postoperative hospital stay and the total cost of admission in the NPDI group were significantly lower than the traditional group (p < .001). CONCLUSION: Negative pressure drainage-assisted irrigation used in the treatment of MSI can shorten the postoperative hospital stay, reduce the total cost of admission, and show favorably clinical effect. It is a clinically recommended method for MSI.

Association between forkhead box E1 polymorphisms and risk of non-syndromic cleft lip with or without cleft palate: A meta-analysis.

OBJECTIVE: The purpose of the present work was to investigate the association between forkhead box E1 (FOXE1) and the risk of non-syndromic cleft lip with or without cleft palate (NSCL/P). MATERIALS AND METHODS: Relevant studies were searched in several professional databases up to 31 July 2019. The pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using a fixed-effect model or a random-effect model to analyse the relationship between FOXE1 polymorphisms and NSCL/P. RESULTS: A total of four single nucleotide polymorphisms (SNPs), including rs3758249, rs4460498, rs1443434 and rs10217225, were analysed. The overall findings showed that FOXE1 rs4460498 was statistically associated with NSCL/P (including cleft lip with or without cleft palate (CL/P) and cleft palate only (CPO)). Genotypes CC and CT of rs4460498 were significantly more closely correlated with NSCL/P (including CL/P and CPO) than genotype TT (NSCL/P: TT vs CC, OR = 0.630, P = .000; TT vs TC + CC, OR = 0.775, P = .020; CL/P: TT vs CC, OR = 0.664, P = .000; TT vs TC + CC, OR = 0.738, P = .006. CPO: TT vs CC, OR = 0.761, P = .027; TT vs TC + CC, OR = 0.792, P = .045). For rs10217225, only the TT genotype might have contributed to the elevated risk of CL/P (TT vs CC OR = 2.236, P = .000). The other FOXE1 polymorphisms were not associated with NSCLP, CL/P or CPO. CONCLUSION: The meta-analysis provided confirmation that the polymorphism of FOXE1 rs10217225 was correlated with an increased risk of CL/P, and the polymorphism of FOXE1 rs4460498 was a protective factor for NSCL/P, including CLP and CPO.

Longitudinal Study of Scar Hyperplasia Formation Following Cleft Lip Wound Healing.

The purpose of this study was to observe the hyperplasia trend of scar after the cleft lip surgery in a rabbit animal model, and determine the time-point of the highest hypertrophic degree of scar after cleft lip repair. Forty New Zealand white rabbits from the same offspring were used to establish a cleft lip wound healing model using Millard surgery procedure. The scar volumes were measured and granulation tissues were observed visually in the 2, 3, 4, and 5 weeks after operation. The scar tissues were harvested at the indicated time-points. Immunohistochemical (IHC) and Western Blot analyses were performed to detect the expression level of α-smooth muscle actin (α-SMA) in the scar tissue. The scars shrunk and the volumes reduced at 3 to 4 weeks after surgery; however, at 5 weeks postsurgery, the volumes increased. IHC and Western blot analyses indicated the expression of α-SMA was significantly enhanced 3 to 4 weeks, but reduced in the 5 weeks after surgery. Overall, the degree of scar hyperplasia after cleft lip surgery in rabbits was normally distributed and the scarring was most severe in the 3 to 4 weeks after cleft lip surgery. The study confirms a novel animal model for the assessment of therapies for the treatment of scar hyperplasia of human cleft lip in future.

Intermittent Stretching and Osteogenic Differentiation of Bone Marrow Derived Mesenchymal Stem Cells via the p38MAPK-Osterix Signaling Pathway.

AIMS: The relationship between the p38MAPK signaling pathway and osterix in osteogenic differentiation of BMMSCs subjected to intermittent stretching was investigated. METHODS: BMMSCs derived from C57BL/6J mice were divided into the following groups: 1) control, 2) stretch, and 3) SB203580+stretch (SB203580 is a p38MAPK signal pathway inhibitor). BMMSCs were exposed to an intermittent mechanical strain of 0.8% (8000µ strain) at 0.5 Hz, twice a day for 30 min each application. BMMSCs were harvested on days 1, 3, and 5 post-treatment. The expression of ALP, COL I, OCN, and osterix mRNA was assessed utilizing RT-PCR while the expression of P-p38MAPK and osterix protein was assessed by Western blot analysis. The osterix gene in mouse BMMSCs was knocked down using RNAi technology and its protein expression was also assessed by Western blot. RT-PCR was used to detect ALP, COL I, and OCN mRNA expression. RESULTS: Intermittent stretching was found to promote expression of ALP, COL I, OCN, and osterix mRNA. Silencing the osterix gene was found to reduce levels of ALP, COL I, and OCN mRNA. Western blot analysis demonstrated that the levels of osterix and P-p38MAPK proteins in the stretch group were significantly higher than in the control group (P<0.05). There was less expression of ALP, COL I, OCN, and osterix mRNA in the SB203580+stretch group than in the control and stretch groups. CONCLUSIONS: Data demonstrate that intermittent stretching promotes osteogenic differentiation of BMMSCs, and the p38MAPK-osterix pathway has an important role in the control of osteogenesis-related gene expression.

Evaluation of Bone Height and Bone Mineral Density Using Cone Beam Computed Tomography After Secondary Bone Graft in Alveolar Cleft.

The purpose of this study was to assess the optimal timing of subsequent dental implant placement and orthodontics after alveolar bone grafting (ABG) in patients with unilateral complete clefts of the alveolar process. Iliac bone graft surgery was performed on 60 patients. Bone mineral density (BMD) and height of the ABG areas were assessed using cone beam computed tomography at 3 and 6 months postoperatively. The heights of the labial and palatal bone graft areas were classified using the modified Bergland classification. The study found that there was no change in BMD between 3 months (mean ±â€ŠSD: 406.51 ±â€Š71.28 Hounsfield units [HU]) and 6 months (409.53 ±â€Š46.37 HU; P = 0.381). Significant changes in the distribution of bone height classifications were observed in the labial and palatal sides of the ABG between 3 and 6 months (P = 0.025 for labial bone height, P = 0.008 for palatal bone height). These results indicate that the alveolar density remained stable between 3 and 6 months, whereas bone height level declined during that period after ABG, the latter indicating bone graft absorption over time. It is, therefore, suggested that subsequent orthodontic or dental implants be placed 3 months after ABG rather than at 6 months or later.

Soft tissue perineurioma of the tongue: report of a case and review of the literature.

Perineurioma is a rare benign tumor of the peripheral nervous system distinct from schwannomas and neurofibromas. It may be intraneural or extraneural (in the soft tissue). Extraneural soft tissue perineuriomas are uncommon; rare cases have been reported in the oral cavity. We present a case of soft tissue perineurioma in the tip of the tongue. The tumor was characterized by slender spindle cells, arranged in short fascicles or whorls, and focal areas showing a distinct storiform pattern. Tumor cells showed the immunohistochemical profile of perineurial cells, including epithelial membrane antigen. Smooth muscle actin, S-100, and CD34 were not expressed by the tumor cells. The tumor was surgically excised and in 2 years there has been no recurrence. Knowledge of the tumor in the oral cavity is important to reach a correct diagnosis and to avoid unnecessary aggressive local excision.

CA1 Modulates the Osteogenic Differentiation of Dental Follicle Stem Cells by Activating the BMP Signaling Pathway In Vitro.

BACKGROUND: Carbonic anhydrase 1 (CA1) has been found to be involved in osteogenesis and osteoclast in various human diseases, but the molecular mechanisms are not completely understood. In this study, we aim to use siRNA and lentivirus to reduce or increase the expression of CA1 in Dental follicle stem cells (DFSCs), in order to further elucidate the role and mechanism of CA1 in osteogenesis, and provide better osteogenic growth factors and stem cell selection for the application of bone tissue engineering in alveolar bone fracture transplantation. METHODS: The study used RNA interference and lentiviral vectors to manipulate the expression of the CA1 gene in DFSCs during in vitro osteogenic induction. The expression of osteogenic marker genes was evaluated and changes in CA1, alkaline phosphatase (ALP), Runt-related transcription factor 2 (RUNX2), and Bone morphogenetic proteins (BMP2) were measured using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting (WB). The osteogenic effect was assessed through Alizarin Red staining. RESULTS: The mRNA and protein expression levels of CA1, ALP, RUNX2, and BMP2 decreased distinctly in the si-CA1 group than other groups (p < 0.05). In the Lentivirus-CA1 (LV-CA1) group, the mRNA and protein expressions of CA1, ALP, RUNX2, and BMP2 were amplified to varying degrees than other groups (p < 0.05). Apart from CA1, BMP2 (43.01%) and ALP (36.69%) showed significant upregulation (p < 0.05). Alizarin red staining indicated that the LV-CA1 group produced more calcified nodules than other groups, with a higher optical density (p < 0.05), and the osteogenic effect was superior. CONCLUSIONS: CA1 can impact osteogenic differentiation via BMP related signaling pathways, positioning itself upstream in osteogenic signaling pathways, and closely linked to osteoblast calcification and ossification processes.

Comparative study of stress characteristics around the adjacent teeth tissues during insertion of mini-screws with different insertion angles: A three-dimensional finite element study.

With a limited alveolar bone position, there is a high risk that mini-screws (MS) implants could cause damage to the adjacent teeth. To reduce this damage, the position and tilt angle of the MS must be optimized. The aim of this study was to assess the effect of MS implantation angle on the stress exerted on adjacent periodontal membrane and roots. A three-dimensional finite element model containing dentition, periodontal ligament, jaw and MS were established based on the CBCT images and MS scanning data. The MS was first inserted perpendicular to the surface of the bone at specific locations and then tilted at an angle of 10° and 20° to the mesial and distal teeth, respectively. The stress distribution in the periodontal tissue of the adjacent teeth was analyzed after MS implantation at different angles.The stress on the adjacent tooth root and periodontal ligament was most uniformly distributed when the MS was inserted vertically. It changed 9.4-97.7% when the axis of MS was tilted at 10-degree and 20-degree angles from the point of vertical insertion. The stresses experienced by the periodontal ligament and the root are similar. When the horizontal angle of the MS insertion was changed, the MS was closer to the adjacent tooth, resulting in greater stress near the PDL and root. It was recommended to insert the MS vertically into the alveolar bone surface to avoid root damage due to excessive stress.

Effect of a digital guide on the positional accuracy of intermaxillary fixation screw implantation in orthognathic surgery.

BACKGROUND: Intermaxillary fixation screw (IMFS) implantation is a common procedure in orthognathic surgery (OGS) performed to the temporary maxillary-mandibular fixation and stable bite relationships. The study aims to assess the accuracy of IMFS implantation with a digital guide to reduce the occurrence of root damage. METHODS: This prospective study involved 40 patients undergoing OGS at the Affiliated Hospital of Qingdao University from August 2017 to May 2021. The patients were randomly divided into two groups according to whether the IMFS implantation was with or without digital guide (20 patients in the experimental group and 20 controls). The digital guides used in the experimental group were designed according to a virtual implantation plan and printed using stereolithography. In the control group, IMFSs were directly implanted by a surgeon based on clinical experience. Postoperatively, cone-beam computed tomography was performed to compare root proximity of IMFSs between the two groups and verify the accuracy of IMFS placement. RESULTS: In the experimental group, there was no case of root damage, the incidence of the periodontal ligament (PDL) injured was 22.1%, and 77.9% IMFSs were placed without contacting adjacent anatomic structures. In the control group, the incidence of root damage had been up to 20.8%, 31.7% IMFSs injured the PDL, and only 47.5% IMFSs were placed between the roots (P < 0.001). CONCLUSION: IMFSs can be placed more accurately with surgical guides, reducing the incidence of root and PDL damages.

Inhibition of p38 mitogen-activated protein kinases may attenuate scar proliferation after cleft lip surgery in rabbits via Smads signaling pathway.

BACKGROUND: Cleft lip repair surgery always results in visible scarring. It has been proved that scar formation can be reduced by inhibiting the p38 mitogen-activated protein kinases (p38MAPKs) signaling pathway. However, the interaction between p38MAPK and Smads in scar formation is still controversial. METHODS: This study was designed to investigate whether inhibition of p38MAPK reduces postoperative scar formation of cleft lips on rabbits via the Smads signaling pathway. Scar models in rabbits after cleft lip surgery were created and their fibroblasts were extracted. Then the expression of p38MAPK was disturbed by adenovirus in vitro and Vivo. The scar thickness was measured and scar tissues were excised for Sirius red staining and immunohistochemistry to detect the expression of type I collagen (col I), type III collagen (col III), and α-smooth muscle actin (α-SMA). The underlying mechanisms of p38MAPK knockdown on the extracellular matrix and Smad signaling pathway were invested in vitro using the EdU assay, Western blot, RT PCR, and immunofluorescence. RESULTS: p38MAPK knockdown suppresses the expression of p-smad3 and p-smad2 in fibroblasts, modulating the expression of its target genes, such as α-SMA, col I, and col III. When Ad-P38MAPK-1 was injected into lip scar, it reduced the expression of scar-related genes and scar thickness when compared to the negative control groups. CONCLUSIONS: In rabbits, inhibiting p38MAPK expression prevents scar proliferation through inhibiting the Smad signaling pathway after cleft lip surgery.

Chemical constituents from the stem of Ficus pumila.

A new biphenyl compound: 5-aldehyde-4'-hydroxy-2,2'-dimethoxybiphenyl (1), along with 11 known phenolic compounds (2-12) were isolated from the stem of Ficus pumila Linn. Their structures were established by spectroscopic methods, including MS, UV, IR, 1 D and 2 D NMR. Compounds 4 and 10 showed weakly cytotoxicity against MCF-7, with IC50 values of 32.5 and 37.3 µM, respectively.

Adult isolated congenital anterior urethrocutaneous fistula.

Isolated congenital anterior urethrocutaneous fistula (CAUF) is an extremely rare deformity and few cases have been reported in the English language literature. Moreover, adult CAUF has not been reported up to now. We present a rare adult patient with this unusual isolated CAUF deformity. The possible etiology and treatment strategy are discussed.

Dopamine agonist responsive burning mouth syndrome: Report of eight cases.

BACKGROUND: Burning mouth syndrome (BMS) is characterized by burning sensation of the oral mucosa. There is a lack of effective treatment. In recent years, a special subtype of BMS has been reported, in which oral burning sensation is alleviated after chewing, speaking, or dopaminergic drug delivery. Currently, there are few reports about the subtype of BMS in China. This study was a retrospective analysis of the clinical data of BMS patients sensitive to dopamine agonist at our hospital, aiming to improve the recognition on this disease. CASE SUMMARY: Eight patients diagnosed with dopamine agonist responsive BMS at the Liaocheng People's Hospital from January 1, 2017 to June 30, 2020 were recruited. The clinical manifestations, treatment, and prognosis were retrospectively analyzed. There were three male and five females in the eight patients. The median age was 56 years (range, 46-65 years). All the eight patients showed burning pain in the mouth. The symptoms were mild in the morning and severe in the evening, and alleviated after chewing, talking, and other oral activities. Four patients were accompanied by restless legs syndrome (RLS). Family history of RLS was positive in two patients. All patients were treated with pramipexol, and symptoms were basically relieved after 2-8 wk. CONCLUSION: Dopamine agonist responsive BMS is a special subtype of BMS, which is alleviated after oral activities. Dopamine receptor agonist is an effective treatment.

Clinical study on obstructive sleep apnea following pharyngeal flap surgery.

OBJECTIVES: This study aims to investigate the incidence and severity of obstructive sleep apnea (OSA) in cleft patients with velopharyngeal insufficiency (VPI) after pharyngeal flap surgery (PFS) and explore the influence of operation age. METHODS: A retrospective study was conducted in 82 cleft patients after PFS. The patients were divided into two groups according to their age at the time of surgery. The incidence and severity of OSA were assessed at least 1.2 years (mean 6.0 years) postoperatively by polysomnography (PSG). RESULTS: The incidence rates of OSA were 20% in the adult group and 31% in the child group. No significant difference was found between the two groups (P=0.289). Patients with OSA in the adult and child groups were classified into different levels of severity (mild, moderate, severe) according to the apnea hypoventilation index (AHI). No statistically significant difference in the severity of OSA was found between the two groups (P=0.079). CONCLUSIONS: Some patients still have OSA average of 6.0 years after PFS, and operation ageis unrelated to the incidence and severity of OSA.

Treatment of oral lichen planus by surgical excision and acellular dermal matrix grafting: Eleven case reports and review of literature.

BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory disorder, and it can affect normal oral function. The conventional treatments for OLP are not always effective, and relapse easily occurs. Therefore, treatment of OLP is difficult and challenging. In this study, we evaluated over a long period the clinical efficacy of surgical excision and acellular dermal matrix (ADM) grafting in patients with refractory OLP. CASE SUMMARY: Eleven patients with refractory OLP underwent a standardized protocol of surgical excision and ADM grafting. The condition of the area of the grafted wound, the intraoperative maximum mouth opening, pain, and clinical healing were assessed at postoperative follow-up visits. All patients had a flat surgical area with similar mucosal tissue coverage and local scar formation. Patients had no irritation and pain in their mucous membranes when eating acidic and spicy food. All patients' mouth openings returned to normal within 2-6 mo after surgery. During follow-up, none of the patients had recurrence of OLP after surgery. The longest follow-up was 11 yr and the shortest was 6 mo, and none of the patients relapsed during follow-up. CONCLUSION: Surgical excision and ADM grafting could be an effective method to treat refractory OLP.

Development and gene expression of C57BL/6 mouse embryo palate shelves in rotary organ culture.

The aim of the present study was to improve methods for the suspension culture of mouse palatal shelves by comparing the expression of platelet-derived growth factor receptor (PDGFR)-α in palatal shelves in vivo, to that in vitro. The palatal shelves of C57BL/6 mouse embryos were obtained on gestation days (GDs) 13.5, 14.5, 15.0 and 15.5 for in vivo experiments. The palatal shelves were removed and observed under a stereomicroscope to investigate palatal development. For in vitro experiments, the palatal shelves were dissected under a stereomicroscope on GD 13.5 and then subjected to rotary culture for 0, 24, 36 or 48 h. The expression of PDGFR-α at different time points was detected by immunohistochemical staining and western blot analysis. Both methods of analysis displayed PDGFR-α expression in mesenchymal and epithelial cells at GD 13.5, 14.5, 15.0 and 15.5, in vivo and in vitro. The level of PDGFR-α expression peaked on GD 14.5. The expression of PDGFR-α in palatal shelves in in vitro rotary culture was consistent with that in vivo. Therefore, the novel technique of palatal rotary organ culture presented in the current study could provide a good model for studying the mechanism of pathological palatal fusion in vitro. Additionally, the present study further confirmed that PDGFR-α gene expression was associated with the development of palatal shelves.

Outcomes of bone morphogenetic protein-2 and iliac cancellous bone transplantation on alveolar cleft bone grafting: A meta-analysis.

BACKGROUND: To systematically evaluate the effect of bone morphogenetic protein-2 (BMP-2) and iliac cancellous bone graft (ICBG) on alveolar cleft bone grafting (ACBG) in cleft lip and palate. METHOD: Online databases were searched for case-control studies related to the application of BMP-2 and ICBG in ACBG. RESULT: Meta-analysis showed no significant statistical difference in the filling rate (OR = 4.1, 95% CI (0.06, 2.63)), the volume of bone graft area (OR=-0.42, 95% CI (-1.44, 0.60)), the height of bone graft area (OR = -21.38, 95% CI (-23.00, -19.76)), the density of bone graft area (OR = 0.43, 95% CI (-0.79, 1.64)), the failure rate of bone graft (OR = 0.02, 95% CI (-0.03, 0.06)), infection after operation, and the rate (OR = 0.20, 95% CI (0.05, 0.73)) and the incidence of postoperative oronasal fistula (OR = 4.1, 95% CI (0.06, 2.63)) between BMP-2 and ICBG in ACBG. However, there were obvious statistical differences in operative time (OR = -3.64, 95% CI (-7.35, 0.06)) and the length of hospital stay (OR = -1.97, 95% CI (-2.41, -1.53)). CONCLUSION: The meta-analysis shows that there is no significant difference between BMP-2 and ICBG in filling rate, volume, density, failure rate, and the occurrence of oronasal fistula after ACBG. There were significant differences between BMP-2 and ICBG in the operation time and hospitalization time of ACBG. Compared with ICBG bone graft, BMP-2 has more advantages in ACBG such as remaining area height, postoperative infection rate, operative time, and length of hospital stay.