The role and mechanism of tight junctions in the regulation of salivary gland secretion.

Tight junctions (TJs) are cell-cell interactions that localize at the most apical portion of epithelial/endothelial cells. One of the predominant functions of TJs is to regulate material transport through paracellular pathway, which serves as a selective barrier. In recent years, the expression and function of TJs in salivary glands has attracted great interest. The characteristics of multiple salivary gland TJ proteins have been identified. During salivation, the activation of muscarinic acetylcholine receptor and transient receptor potential vanilloid subtype 1, as well as other stimuli, promote the opening of acinar TJs by inducing internalization of TJs, thereby contributing to increased paracellular permeability. Besides, endothelial TJs are also redistributed with leakage of blood vessels in cholinergic-stimulated submandibular glands. Furthermore, under pathological conditions, such as Sjögren's syndrome, diabetes mellitus, immunoglobulin G4-related sialadenitis, and autotransplantation, the integrity and barrier function of TJ complex are impaired and may contribute to hyposalivation. Moreover, in submandibular glands of Sjögren's syndrome mouse model and patients, the endothelial barrier is disrupted and involved in hyposecretion and lymphocytic infiltration. These findings enrich our understanding of the secretory mechanisms that link the importance of epithelial and endothelial TJ functions to salivation under both physiological and pathophysiological conditions.

SHED-exos promote saliva secretion by suppressing p-ERK1/2-mediated apoptosis in glandular cells.

OBJECTIVES: Confirm that stem cells from human exfoliated deciduous teeth-derived exosomes (SHED-exos) can limit inflammation-triggered epithelial cell apoptosis and explore the molecular mechanism. METHODS: SHED-exos were injected into the submandibular glands (SMGs) of non-obese diabetic (NOD) mice, an animal model of Sjögren's syndrome (SS). Cell death was evaluated by western blotting and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling staining. RESULTS: SHED-exos treatment promoted the saliva flow rates of NOD mice, accompanied by decreased cleaved caspase-3 levels and apoptotic cell numbers in SMGs. SHED-exos inhibited autophagy, pyroptosis, NETosis, ferroptosis, necroptosis and oxeiptosis marker expression in SS-damaged glands. Mechanistically, Kyoto Encyclopedia of Genes and Genomes analysis of exosomal miRNAs suggested that the rat sarcoma virus (RAS)/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway might play an important role. In vivo, the expression of Kirsten RAS, Harvey RAS, MEK1/2 and p-ERK1/2 was upregulated in SMGs, and this change was blocked by SHED-exos treatment. In vitro, SHED-exos suppressed p-ERK1/2 activation and increased cleaved caspase-3 and apoptotic cell numbers, which were induced by IFN-γ. CONCLUSION: SHED-exos suppress epithelial cell death, which is responsible for promoting salivary secretion. SHED-exos inhibited inflammation-triggered epithelial cell apoptosis by suppressing p-ERK1/2 activation, which is involved in these effects.

Symmetrical Midfacial Growth After Pediatric Mandibular Reconstruction With Free Fibula Flap.

BACKGROUND: Free fibula is the workhorse flap for mandibular reconstruction and is increasingly being used in pediatric patients. However, craniomaxillofacial growth and development involve interdependent processes, and it remains unknown whether mandibular reconstruction with free fibula allows symmetric growth of the midface. PURPOSE: The study evaluated midfacial symmetry after pediatric mandibular defect reconstruction. STUDY DESIGN, SETTING, SAMPLE: This retrospective cohort study included pediatric patients aged ≤14 years who underwent mandibular reconstruction with free fibula flap. Postoperative computed tomography data were obtained at predefined follow-up time points. Midfacial symmetry was evaluated based on 3-dimensional (3D) cephalometry. PREDICTOR VARIABLE: The predictor variable was the side of the midface (affected or healthy side relative to the mandibular defect). MAIN OUTCOME VARIABLES: The primary outcome variable was postoperative midfacial symmetry (at 1 week, 6 months, 1 year, 2 years, and >3 years, or after the age of 18 years), assessed in horizontal, vertical, and anteroposterior dimensions using 3D cephalometry. Another outcome variable was patient satisfaction based on a self-evaluation using visual analog scoring. COVARIATES: Sex, age, diagnosis, and type of denture restoration. ANALYSES: Paired t tests were performed to assess the relationship between the predictor and outcome variables, with the significance level of P < .05. RESULTS: A total of 13 patients were included in this study (9 males and 4 females; mean age: 12.23 ± 2.39 years). The average distance from upper first molar point (U6) to the horizontal plane on the affected side became greater than on the healthy side (difference: 0.7 ± 0.5 mm to 1.6 ± 1.4 mm, P < .05), while the average distance from pterygomaxillary fissure to coronal plane on affected side became shorter than that on the healthy side (difference: 0.6 ± 0.6 mm to 1.2 ± 1.1 mm, P < .05) from 1 year after the surgery. There were no statistically significant differences in the remaining measurements between the 2 sides (P > .05). All the patients were satisfied with their postoperative facial symmetry. CONCLUSIONS AND RELEVANCE: There were no severe midface deformities after pediatric mandibular reconstruction with free fibula flap. Meanwhile, pediatric mandibular reconstruction and proper occlusion could promote midfacial growth and symmetry.

Vascularized Free Fibular Flap in Oral and Maxillofacial Reconstruction: A 20-year Experience at a Single Institution Using 2640 Flaps.

BACKGROUND: This retrospective study reviewed all patients who underwent oral and maxillofacial reconstruction with fibular flaps in the last 2 decades at a single hospital. MATERIALS AND METHODS: We reviewed all patients with fibular flaps from 1999 to 2018. The following data were collected: sex; age; reconstruction region; diagnosis; the number of days spent in the hospital after surgery; time spent using a tourniquet for harvesting a fibula flap; vessels at the recipient site; the prevalence of unplanned reoperations; the prevalence of flap failure; history of preoperative radiotherapy; virtual surgical planning; segments of the fibula. RESULTS: In total, 2640 patients were included. The mean age was 45.5 years. The most prevalent region of reconstruction was the mandible (n=2347, 88.9%). The most common diagnosis was squamous cell carcinoma (n=1057, 40.0%). The mean number of days spent in the hospital after surgery decreased year-by-year from 18.3 days to 10.4 days. The first choice of recipient artery was the facial artery (n=1643, 62.2%) and that of the recipient vein was the external jugular vein (n=1196, 45.3%). The prevalence of surgical success was 97.6%. Prevalence of unplanned reoperations was 7.5%. CONCLUSIONS: The fibular flap was a good choice for oral and maxillofacial bony reconstruction in most cases.

Factors influencing the accuracy of multimodal image fusion for oral and maxillofacial tumors: a retrospective study.

BACKGROUND: Ensuring high accuracy in multimodal image fusion for oral and maxillofacial tumors is crucial before further application. The aim of this study was to explore the factors influencing the accuracy of multimodal image fusion for oral and maxillofacial tumors. METHODS: Pairs of single-modality images were obtained from oral and maxillofacial tumor patients, and were fused using a proprietary navigation system by using three algorithms (automatic fusion, manual fusion, and registration point-based fusion). Fusion accuracy was evaluated including two aspects-overall fusion accuracy and tumor volume fusion accuracy-and were indicated by mean deviation and fusion index, respectively. Image modality, fusion algorithm, and other characteristics of multimodal images that may have potential influence on fusion accuracy were recorded. Univariate and multivariate analysis were used to identify relevant affecting factors. RESULTS: Ninety-three multimodal images were generated by fusing 31 pairs of single-modality images. The interaction effect of image modality and fusion algorithm (P = 0.02, P = 0.003) and thinner slice thickness (P = 0.006) were shown to significantly influence the overall fusion accuracy. The tumor volume (P < 0.001), tumor location (P = 0.007), and image modality (P = 0.01) were significant influencing factors for tumor volume fusion accuracy. CONCLUSIONS: To ensure high overall fusion accuracy, manual fusion was not preferred in CT/MRI image fusion, and neither was automatic fusion in image fusion containing PET modality. Using image sets with thinner slice thickness could increase overall fusion accuracy. CT/MRI fusion yielded higher tumor volume fusion accuracy than fusion containing PET modality. The tumor volume fusion accuracy should be taken into consideration during image fusion when the tumor volume is small and the tumor is located in the mandible.

Double-Barrel Fibula Flap Versus Vascularized Iliac Crest Flap for Mandibular Reconstruction.

PURPOSE: The double-barrel fibula flap and vascularized iliac crest flap are both commonly used for mandibular reconstruction. The present study compared the usage and reconstruction outcomes of transplanted bone with these 2 methods. PATIENTS AND METHODS: The data from 30 patients who had undergone mandibular osteotomy and reconstruction were retrospectively reviewed. Of the 30 patients, 20 received a vascularized iliac crest flap (group A) and 10 received a double-barrel fibula flap (group B). The following variables were compared between the 2 groups: volume of bone flap (VBF), volume of effective bone flap (VEBF; ie, overlap between the volume of the ideal mandible [VIM] and the VBF), usage of the bone flap (VEBF divided by the VBF), mandibular reconstruction rate (VEBF divided by the VIM), volume of needless bone flap (VNBF; ie, VBF minus VEBF; the VNBF included the volume of needless buccal bone flap [VNBBF] and the volume of needless lingual bone flap [VNLBF]), percentage of alveolar crest restoration (PACR; ie, effective bone flap width divided by ideal alveolar crest width), and height of the bone flap (HBF). The independent-samples t test and the χ2 test were used to compare the variables between the 2 groups. Statistical significance was at P ≤ .05. RESULTS: Usage of the bone flap and the length of the mandibular defect were significantly greater in group B than in group A (P = .039 and P < .001, respectively). The VBF, VNBF, and VNLBF were significantly greater in group A than in group B (P < .001 for both). The mandibular reconstruction rate, VNBBF, PACR, HBF, and tooth implantation rate were comparable between the 2 groups. CONCLUSIONS: The double-barrel fibula flap can effectively restore the height of the alveolar crest, reconstruct longer mandibular defects, and provide a better buccal and lingual appearance compared with the vascularized iliac crest flap. Although the vascularized iliac crest flap can provide sufficient bone quantity, it must be contoured to the mandible.

Regeneration of the Neocondyle After Free Fibular Flap Reconstruction of the Mandibular Condyle.

PURPOSE: Shifting of the flap position after condylar reconstruction with free fibular flaps is known to occur, but its long-term effects on postoperative esthetic outcomes have not been sufficiently reported. Therefore, in this study, we evaluated the long-term morphologic stability of the free fibular flap neocondyle. PATIENTS AND METHODS: This was a retrospective cohort study. The primary outcome variables were neocondyle regeneration and neocondyle position including the distance between the glenoid fossa and the initial neocondyle (Fo-Co), the distance between the glenoid fossa and the stable neocondyle (Fo-Co'), and shifting of the neocondyle (defined as the distance between the stable neocondyle and the initial neocondyle). The primary predictor variable was time. The other variables were age, gender, diagnosis, and number of fibular segments. Correlation analysis between the predictor variables and outcome variables was performed. RESULTS: The sample was composed of 26 patients (11 male and 15 female patients) with a mean age of 31 years. Diagnosis and number of fibular segments were significantly associated with Fo-Co and Fo-Co' (P < .05). Among the 26 patients, only 11 showed neocondyle regeneration at follow-up (group A) whereas 15 did not (group B). Neocondyle regeneration was significantly associated with patient age (P < .01). Stable Fo-Co and stable time were significantly associated with neocondyle regeneration (P < .05). The mean stable time was significantly shorter in group A (3.64 ± 1.12 months) than in group B (6.67 ± 3.85 months) (P < .05), and the mean Fo-Co' was significantly shorter in group A (13.65 ± 3.94 mm) than in group B (20.68 ± 8.87 mm) (P < .05). CONCLUSIONS: The possibility of neocondyle regeneration is higher in pediatric patients than in adults. Neocondyle regeneration could result in the movement of the neocondyle toward the glenoid fossa with a shorter stable time, which could improve neocondyle repositioning. Repositioning of the neocondyle with free fibular flaps for mandibular condyle defects is a self-adaption process for temporomandibular joint function.

Selection of Guiding Plate Combined With Surgical Navigation for Microsurgical Mandibular Reconstruction.

PURPOSE: The present study summarized selection of guiding plate combined with surgical navigation for microsurgical mandibular reconstruction. METHODS: Data from preoperative maxillofacial enhanced computed tomography (CT) scans were imported to ProPlan CMF. The authors performed virtual mandibulectomy and superimposed 3-dimensional (3D) iliac images on mandibular defects. Guiding plates including mandibular fixation device, reconstruction plate, guiding model, and occlusal splint for various mandibular hemimandibular central lateral (HCL) defects were fabricated to fix bilateral residual mandible. The model was scanned, and data were imported into ProPlan CMF and the intraoperative navigation system. Through landmark points upon the guiding plate, position of the residual mandible was determined during surgical navigation. Intraoperative navigation was used to implement the virtual plan. Sagittal, coronal, axial, and 3D reconstruction images displayed by the navigation system were used to accurately determine osteotomy sites and osteotomy trajectory during surgery. Surgical probe guidance was used to mark the osteotomy line and transfer the virtual procedure to real-time surgery. Accuracy was evaluated using chromatographic analysis. RESULTS: Different guiding plates combined with surgical navigation could be used for various mandibular defects, including mandibular fixation devices for LCL defects, reconstruction plates for LC/L/C defects, and guiding models and occlusal splints for H/L/LC defects (including mandibular ramus). In our study, average and largest shift of the mandible and osteotomy site was <5 mm. CONCLUSION: The authors summarized different ways of combining guiding plates with surgical navigation for reconstruction of various mandibular defects, which could improve clinical outcomes of this procedure with high accuracy.

Stem cells  from exfoliated  deciduous  teeth alleviate hyposalivation caused by Sjögren syndrome.

OBJECTIVES: To evaluate the effect of stem cells  from  exfoliated  deciduous  teeth on the hyposalivation caused by Sjögren syndrome (SS) and investigate the mechanism. METHODS: Stem cells were injected into the tail veins of non-obese diabetic mice, the animal model of SS. The saliva flow was measured after pilocarpine intraperitoneal injection. Apoptosis and autophagy were evaluated by TUNEL and Western blot. Lymphocyte proportions were detected by flow cytometer. RESULTS: Fluid secretion was decreased in 21-week-old mice. Stem cell treatment increased fluid secretion, alleviated inflammation in the submandibular glands and reduced inflammatory cytokine levels in the serum, submandibular glands and saliva. Stem cells decreased the apoptotic cell number and the expressions of ATG5 and Beclin-1 in the submandibular glands. Stem cells have no effect on other organs. Furthermore, the infused stem cells migrated to the spleen and liver, not the submandibular gland. Stem cells directed T cells towards Treg cells and suppressed Th1 and Tfh cells in spleen lymphocytes. CONCLUSION: Stem cells  from  exfoliated  deciduous  teeth alleviate the hyposalivation caused by SS via decreasing the inflammatory cytokines, regulating the inflammatory microenvironment and decreasing the apoptosis and autophagy. The stem cells regulated in T-cell differentiation are involved in the immunomodulatory effects.

Outcomes of Zygomatic Complex Reconstruction With Patient-Specific Titanium Mesh Using Computer-Assisted Techniques.

PURPOSE: Zygomatic complex defects after extensive maxillectomy can cause severe esthetic and functional deformities. Patient-specific titanium mesh fabricated using a computer-assisted technique is a promising method for such midface reconstruction. The aim of this study was to evaluate the application and clinical outcomes of this technique. PATIENTS AND METHODS: This was a retrospective study that included 9 patients with zygomatic complex defects after extensive maxillectomy from 2015 through 2017 at the authors' institution. A 3-dimensional stereo model was obtained based on mirror images of the unaffected side to fabricate a patient-specific titanium mesh using computer-assisted design and manufacturing. Titanium mesh was used to restore the contour of the zygomatic complex with free flap reconstruction after tumor resection. Anterolateral thigh flaps were used in 8 cases and a myocutaneous fibula flap was used in 1 case. Symmetry of the zygomatic complex was evaluated by measuring the zygomatic eminence on the postoperative computed tomogram, and complications were recorded during follow-up visits. Facial symmetry was self-evaluated and scored. RESULTS: Mean duration for follow-up was 27.3 months (range, 15 to 39 months). Mean deviation of the zygomatic eminence between the reconstructed and unaffected sides was 1.4 ± 0.5 mm. No significant difference was noted in the zygomatic eminence between the reconstructed and unaffected sides (P = .591). Titanium mesh exposure occurred in only 1 patient after radiotherapy. There were no other remarkable complications. All patients were satisfied with their postoperative facial symmetry. CONCLUSION: Patient-specific titanium mesh fabricated using a computer-assisted technique was an alternative option for extensive zygomatic complex reconstruction, resulting in acceptable clinical outcomes. A study with a larger sample and long-term follow-up is needed for the observation of long-term outcomes and risk of titanium mesh-related complications.

Evaluation of Parotid Gland Function Before and After Endoscopy-Assisted Stone Removal.

PURPOSE: To quantify gland function before and after endoscopy-assisted lithectomy for patients with parotid stones and to analyze correlations among different evaluation modalities. MATERIALS AND METHODS: This study investigated 58 patients (27 men and 31 women) with a stone larger than 5 mm or multiple parotid stones who underwent successful endoscopy-assisted surgery at the authors' center from August 2007 through September 2017. Meticulous postoperative manipulations were administered routinely for 3 to 6 months to promote functional recovery of the affected gland. Gland function was evaluated preoperatively and 6 to 36 months (mean, 12 months) postoperatively by sialography, scintigraphy, and sialometry. Statistical analyses were conducted to quantify gland function recovery and to distinguish correlations among the 3 objective tests. RESULTS: Preoperative sialograms exhibited ductal ectasia at the stone site with ductal stenosis anterior to the stone (n = 53) or duct interruption at the stone site (n = 5). Postoperative sialograms of 45 patients without stones were categorized as approximately normal (type I; n = 17); showing ectasia or stenosis of the main duct without persistent contrast on the functional film (type II; n = 16); showing ectasia or stenosis of the main duct with mild contrast retention (type III; n = 6); or showing poor ductal shape with evident contrast retention (type IV; n = 6). Scintigraphy of 23 preoperative and 12 postoperative patients and sialometry of 24 preoperative and 12 postoperative patients indicated severe preoperative impairment and postoperative improvement of gland function. Postoperatively, although no relevant differences in saliva flow rate were found between the 2 sides, scintigraphy showed lower function of the affected gland compared with the control side. Statistical data showed positive correlations among the 3 methods. Sialography intuitively reflected the ductal shape, whereas sialometry and scintigraphy were more sensitive for evaluating gland function. CONCLUSION: For patients with parotid stones, minimally invasive endoscopic surgery and meticulous postoperative manipulations help preserve the glands and facilitate recovery of gland function. The 3 evaluating modalities have certain positive correlations.

Mandibular growth in survivors of pediatric parotid gland carcinoma treated with interstitial brachytherapy.

BACKGROUND: The aim of the study was to present long-term results of mandibular growth in pediatric parotid gland carcinoma survivors treated with interstitial brachytherapy. PROCEDURE: Twenty-five survivors of pediatric parotid gland carcinoma treated with iodine-125 seed interstitial brachytherapy were included for quantitative analysis, including three dimensional (3D) cephalometry and measurement of mandibular volume. RESULTS: 3D cephalometry showed that the median fore-and-aft increments of the lengths of the condyle, the ramus, and the body of the mandible were 1.23, 0.19, and 1.66 mm for the affected side, respectively, and were 1.37, 1.95, and 3.42 mm for the unaffected side, respectively. The difference in increments of the ramus was statistically significant between the affected side and the unaffected side (P = 0.003; P < 0.05). Moreover, mandibular volume measurements showed that the median fore-and-aft increments of the volumes of the condyle, the ramus, and the body of the mandible were 290.62, 220.14, and 1706.40 mm3 for the affected side, respectively, and were 269.15, 370.40, and 1469.86 mm3 for the unaffected side, respectively. The difference in increments was statistically significant between the affected side and the unaffected side for the ramus (P = 0.005; P < 0.05) and the body (P = 0.043; P < .05). CONCLUSION: Mandibular growth was affected by interstitial brachytherapy, especially for the ramus, in pediatric parotid gland carcinoma survivors treated with interstitial brachytherapy. Nevertheless, the impact was mild in these survivors.

Parasympathectomy increases resting salivary secretion in normal and irradiated submandibular glands of rats.

Fluid and ion secretion from the submandibular gland (SMG) is mainly regulated by parasympathetic nerves. This study evaluated the effect of parasympathectomy on salivary secretion from normal and irradiated rat SMGs from 1 to 24 wk after denervation. Although stimulated salivary secretion was significantly lower in denervated SMGs compared with contralateral self-controls, the resting salivary flow rates were markedly higher in the denervated SMGs at 1, 12, and 24 wk after denervation. The levels of muscarinic acetylcholine M1 and M3 receptors, as well as of aquaporin 5, were up-regulated. Notably, although irradiated SMGs showed significantly lower resting and stimulated salivary secretion rates than non-irradiated SMGs, the resting salivary secretion rates of the irradiated and denervated SMGs were markedly higher than seen in the irradiated self-control SMGs at 1, 12, and 24 wk after parasympathectomy, and were even higher than seen in the non-irradiated sham-operated rats. The expression of M1 and M3 receptors was similarly elevated. Taken together, our results suggest that parasympathetic denervation increases resting salivary secretion of both normal and irradiated SMGs. This approach might provide a potential modality for relieving radiation-induced xerostomia, which is a common complication following treatment of head and neck cancer.

Three-Dimensional Accuracy of Virtual Planning and Surgical Navigation for Mandibular Reconstruction With Free Fibula Flap.

PURPOSE: Although free fibula flaps are widely used for mandibular reconstruction, their 3-dimensional position is difficult to control during conventional surgery. We aimed to improve this process by using computer-aided design (CAD) and surgical navigation. PATIENTS AND METHODS: We retrospectively reviewed 29 benign tumor patients who underwent primary unilateral mandibular reconstruction with free fibula flap. They were divided into 3 groups: group A, comprising 10 patients, underwent reconstruction based on the surgeon's experience; group B, comprising 7 patients, underwent reconstruction based on CAD; and group C, comprising 12 patients, underwent reconstruction based on CAD and surgical navigation. Condyle and gonion positions and mandibular angles were measured. Operative times were recorded. RESULTS: Among the 17 patients who underwent condylar resection, the average condyle shift was greater in group A than in groups B and C (P < .05). The average gonion shift was greater in groups A and B than in group C (P < .05). The difference between the reconstructed and contralateral mandibular angles was greater in group A than in groups B and C (P < .05). The mean operative time did not differ among the 3 groups. CONCLUSIONS: CAD can guide mandibular angle remodeling and condyle placement. CAD and surgical navigation increase reconstruction accuracy without prolonging operative time.

A New Procedure Assisted by Digital Techniques for Secondary Mandibular Reconstruction With Free Fibula Flap.

PURPOSE: To describe a new procedure assisted by digital techniques for secondary mandibular reconstruction with free fibula flap. METHODS: The 3-dimensional (3D) reconstruction images for vessels were used to demonstrate the vascular diameter and location, which help select the most suitable vein and artery for anastomosis. Maxillary and mandibular stone models of the patient were fabricated and a stable occlusal relationship was determined on an articulator. The 3D tooth model data were scanned using a 3D-optical measuring system, and the obtained stereolithographic (STL) data were imported to Geomagic software. Preoperative maxillofacial and fibular noncontrast-enhanced computed tomography scans were acquired, and the data were imported to ProPlan CMF software. The maxilla and mandible were segmented, and STL data were imported to Geomagic software. The registration function was used to determine the ideal mandibular position. First, with the maxillary position fixed, the maxillary and mandibular models were registered with the maxilla. Then, with the tooth model positions fixed, the mandible was registered with the models. The STL data for the mandible were imported to ProPlan CMF software. Virtual plan and surgical navigation were used to design and correct the mandibular and fibular position. RESULTS: Our technique enabled precise recovery of the original mandibular configuration in this patient. The shift in the reconstructed mandible and fibular segment was <5 mm. CONCLUSIONS: The authors described a new procedure for secondary mandibular reconstruction with a free fibular flap using digital techniques involving surgical navigation, which have the potential to improve the clinical outcomes of this procedure.

Outcomes of Orbital Floor Reconstruction After Extensive Maxillectomy Using the Computer-Assisted Fabricated Individual Titanium Mesh Technique.

PURPOSE: Orbital floor defects after extensive maxillectomy can cause severe esthetic and functional deformities. Orbital floor reconstruction using the computer-assisted fabricated individual titanium mesh technique is a promising method. This study evaluated the application and clinical outcomes of this technique. PATIENTS AND METHODS: This retrospective study included 10 patients with orbital floor defects after maxillectomy performed from 2012 through 2014. A 3-dimensional individual stereo model based on mirror images of the unaffected orbit was obtained to fabricate an anatomically adapted titanium mesh using computer-assisted design and manufacturing. The titanium mesh was inserted into the defect using computer navigation. The postoperative globe projection and orbital volume were measured and the incidence of postoperative complications was evaluated. RESULTS: The average postoperative globe projection was 15.91 ± 1.80 mm on the affected side and 16.24 ± 2.24 mm on the unaffected side (P = .505), and the average postoperative orbital volume was 26.01 ± 1.28 and 25.57 ± 1.89 mL, respectively (P = .312). The mean mesh depth was 25.11 ± 2.13 mm. The mean follow-up period was 23.4 ± 7.7 months (12 to 34 months). Of the 10 patients, 9 did not develop diplopia or a decrease in visual acuity and ocular motility. Titanium mesh exposure was not observed in any patient. All patients were satisfied with their postoperative facial symmetry. CONCLUSION: Orbital floor reconstruction after extensive maxillectomy with an individual titanium mesh fabricated using computer-assisted techniques can preserve globe projection and orbital volume, resulting in successful clinical outcomes.

[Activation of transient receptor potential vanilloid subtype 1 serves as a novel pathway to modulate secretion in submandibular gland].

Our work focused on the studies on the expression and function of transient receptor potential vanilloid subtype 1 (TRPV1) in the submandibular gland. By using reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and immunofluorescence, our data demonstrated the expression and distribution characteristics of TRPV1 in rabbit and human submandibular glands, as well as rat submandibular gland cell line SMG-C6. Furthermore, the possible intracellular signal molecules involved in the TRPV1-modulated saliva secretion were explored. Activation of TRPV1 increased the intracellular Ca(2+) concentration, upregulated the expression of aquaporin 5 (AQP5), the main transporter that mediate water secretion through transcellular pathway, and led to AQP5 redistribution. Extracellular signal-regulated kinase 1/2 (ERK1/2) was involved in the TRPV1-regulated AQP5 content. Besides, TRPV1 activation also modulated the expression, distribution, and function of tight junction protein, and increased paracellular permeability. ERK1/2 and myosin light chain 2 (MLC2) were responsible for the regulation of TRPV1on tight junction properties. Taken together, our work suggested that TRPV1 was a potential target to promote saliva secretion, and activation of TRPV1 might provide a new and safe therapeutic strategy to ameliorate submandibular gland hypofunction.

[Classification and reconstruction of 1,107 cases of maxillary defects].

OBJECTIVE: To investigate the defect types and reconstruction methods of maxillary defects. METHODS: The database of 1,107 cases with maxillary defects in Peking University School and Hospital of Stomatology from January 1985 to December 2010 was established. There construction methods were reviewed. The defect types were classified according to Brown classification system. RESULTS: In the 1,107 cases, 1,104 cases could be classified according to Brown classification system. The most common type was 2a with 559 cases (50.6%). Among all the 1,107 cases, 349 cases were reconstructed with autotransplantation, 443 cases with prosthesis, 107 cases untreated, and 208 patients lost to the follow-up. There was a significant growing trend over time for the application of free flaps and a downward trend of prosthesis. The most popular free flaps were fibular flap (88 cases) and radial forearm flap (75 cases). Rectus abdominis flap and anterolatreal thigh flap were fit for extensive maxillary defects. CONCLUSION: The most common defect type is 2a. Free flap has become the dominant option for maxillary reconstruction. Free flaps could be selected according to the maxillary defect types.

Comparison of epidermal growth factor expression and secretion in human salivary glands.

OBJECTIVE: To investigate the expression and secretion of epidermal growth factor (EGF) in major and minor salivary gland tissues of human subjects and to examine the potential influence of sex and age on EGF expression and secretion. DESIGN: Saliva samples from the oral cavity at rest and after citric acid stimulation, as well as serum samples, were collected from 150 healthy subjects, and the concentrations of EGF were measured with enzyme-linked immunosorbent assay (ELISA) and compared. The expression of EGF mRNA and protein in normal salivary gland tissues was measured by real-time polymerase chain reaction (RT-PCR), Western blot (WB), and immunohistochemistry (IHC). RESULTS: The EGF concentration in acid-stimulated saliva was significantly higher than that in resting saliva (P < 0.001), and significantly higher than that in serum (P < 0.001). No sex difference was observed in EGF levels of whole saliva and serum, whereas the EGF levels in saliva and serum were decreased with age (P < 0.001 and P < 0.001, respectively). The EGF concentration and compound secretion rate (CSR) in resting submandibular glands saliva were significantly higher than those in resting parotid glands saliva (P = 0.002 and P < 0.001, respectively). The EGF was expressed in all major and minor salivary glands and ranked in order of submandibular, parotid, sublingual, and labial glands. CONCLUSION: All salivary glands have the function of secreting EGF, and the submandibular gland is the main source of salivary EGF. Aging is a factor influencing the expression and secretion of EGF.

Long-Term Outcomes after Pediatric Mandibular Reconstruction Using Vascularized Free Fibula Flap.

BACKGROUND: The purpose of this study was to evaluate the long-term outcomes of mandibular reconstruction with vascularized free fibula flap in pediatric patients. METHODS: Consecutive cases of mandibular reconstruction with vascularized free fibula flaps in pediatric patients at Peking University School and Hospital of Stomatology between 1999 and 2019 were reviewed. Postoperative computed tomography (CT) data of all patients were collected at each postoperative follow-up point, and after the age of 18 years. The length and height of the grafted fibula and the length of the remaining mandible were evaluated by measuring the three-dimensional CT data using ProPlan CMF 3.0 software. Lower limb function was evaluated using the Enneking evaluation scale. Facial symmetry was self-evaluated and scored. Statistical analysis was performed on the data obtained. RESULTS: Fourteen patients were included in this study. All flaps were successful. The CT measurement results showed growth in the length of the grafted fibula that reconstructed the mandibular ramus and the residual mandible ( P < 0.05). The height of the grafted fibula remained stable ( P > 0.05). Eight patients were followed up until they were older than 18 years, and the CT measurement results after 18 years showed an essentially symmetric mandible profile ( P > 0.05). All patients were satisfied with their postoperative facial symmetry. Enneking evaluation scores showed good recovery of lower limb functions. CONCLUSIONS: The vascularized free fibula flap for mandibular reconstruction in pediatric patients is safe and reliable. It also provides good cosmetic and functional outcomes, as it demonstrated positive growth. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.