Alveolar ridge preservation of two-wall bone defects using mineralized dentin matrix: An experimental pre-clinical study.

OBJECTIVES: To study bone healing of two-wall bone defects after alveolar ridge preservation using mineralized dentin matrix. MATERIALS AND METHODS: After distal roots extraction of second and fourth premolars (P2, P4) on one lateral mandible in 12 beagles, two-wall bone defects (5 × 5 × 5 mm) were surgically created distally to the remaining mesial roots of P2 and P4. A total of 24 sites were randomly allocated to three groups (implant material- time of execution): mineralized dentin matrix (MDM)-3 m (MDM + collagen membrane; 3 months), MDM-6 m (MDM particles + collagen membrane; 6 months), and C-6 m (collagen membrane only; 6 months). Clinical, radiographic, digital, and histological examinations were performed 3 and 6 months after surgery. RESULTS: The bone healing in MDM groups were better compared to Control group (volume of bone regenerated in total: 25.12 mm3 vs. 13.30 mm3, p = .046; trabecular volume/total volume: 58.84% vs. 39.18%, p = .001; new bone formation rate: 44.13% vs. 31.88%, p = .047). Vertically, the radiological bone level of bone defect in MDM-6 m group was higher than that in C-6 m group (vertical height of bone defect: 1.55 mm vs. 2.74 mm, p = .018). Horizontally, no significant differences in buccolingual bone width were found between MDM and C groups at any time or at any level below the alveolar ridge. The percentages of remaining MDM were <1% in both MDM-3 m and MDM-6 m groups. CONCLUSIONS: MDM improved bone healing of two-wall bone defects and might be considered as a socket fill material used following tooth extraction.

Deep learning-based hyperspectral technique identifies metastatic lymph nodes in oral squamous cell carcinoma-A pilot study.

AIMS: To establish a system based on hyperspectral imaging and deep learning for the detection of cancer cells in metastatic lymph nodes. MAIN METHODS: The continuous sections of metastatic lymph nodes from 45 oral squamous cell carcinoma (OSCC) patients were collected. An improved ResUNet algorithm was established for deep learning to analyze the spectral curve differences between cancer cells and lymphocytes, and that between tumor tissue and normal tissue. KEY FINDINGS: It was found that cancer cells, lymphocytes, and erythrocytes in the metastatic lymph nodes could be distinguished basing hyperspectral image, with overall accuracy (OA) as 87.30% and average accuracy (AA) as 85.46%. Cancerous area could be recognized by hyperspectral image and deep learning, and the average intersection over union (IOU) and accuracy were 0.6253 and 0.7692, respectively. SIGNIFICANCE: This study indicated that deep learning-based hyperspectral techniques can identify tumor tissue in OSCC metastatic lymph nodes, achieving high accuracy of pathological diagnosis, high work efficiency, and reducing work burden. But these are preliminary results limited to a small sample.

Prediction of jaw opening function after mandibular reconstruction using subject-specific musculoskeletal modelling.

BACKGROUND: Mandibular reconstruction patients often suffer abnormalities in the mandibular kinematics. In silico simulations, such as musculoskeletal modelling, can be used to predict post-operative mandibular kinematics. It is important to validate the mandibular musculoskeletal model and analyse the factors influencing its accuracy. OBJECTIVES: To investigate the jaw opening-closing movements after mandibular reconstruction, as predicted by the subject-specific musculoskeletal model, and the factors influencing its accuracy. METHODS: Ten mandibular reconstruction patients were enrolled in this study. Cone-beam computed tomography images, mandibular movements, and surface electromyogram signals were recorded preoperatively. A subject-specific mandibular musculoskeletal model was established to predict surgical outcomes using patient-averaged muscle parameter changes as model inputs. Jaw bone geometry was replaced by surgical planning results, and the muscle insertion sites were registered based on the non-rigid iterative closest point method. The predicted jaw kinematic data were validated based on 6-month post-operative measurements. Correlations between the prediction accuracy and patient characteristics (age, pathology and surgical scope) were further analysed. RESULTS: The root mean square error (RMSE) for lower incisor displacement was 31.4%, and the error for peak magnitude of jaw opening was 4.9 mm. Age, post-operative infection and radiotherapy influenced the prediction accuracy. The amount of masseter detachment showed little correlation with jaw opening. CONCLUSION: The mandibular musculoskeletal model successfully predicted short-range jaw opening functions after mandibular reconstruction. It provides a novel surgical planning method to predict the risk of developing trismus.

Evaluation of joint kinematics in patients with condylar reconstruction using mandibular motion simulation based on intraoral scanning registration.

AIM: To summarize the features of condylar kinematics in patients with condylar reconstruction using a mandibular motion simulation method based on intraoral scanning registration. MATERIALS AND METHODS: Patients undergoing unilateral segmental mandibulectomy and autogenous bone reconstruction as well as healthy volunteers were enrolled in the study. Patients were grouped based on whether the condyles were reconstructed. Mandibular movements were recorded using a jaw tracking system, and kinematic models were simulated after registration. The path inclination of the condyle point, margin of border movement, deviation, and chewing cycle were analyzed. A t test and one-way analysis of variance (ANOVA) were carried out. RESULTS: A total of 20 patients, including 6 with condylar reconstruction and 14 with condylar preservation as well as 10 healthy volunteers were included. The patients with condylar reconstruction showed flatter movement paths of the condyle points. The mean inclination angle of the condylar movement paths of the patients with condylar reconstruction (0.57 ± 12.54 degrees) was significantly smaller than that of those with condylar preservation (24.70 ± 3.90 degrees, P = 0.014) during both maximum opening and protrusion (7.04 ± 12.21 degrees and 31.12 ± 6.79 degrees, respectively, P = 0.022). The inclination angle of the condylar movement paths of the healthy volunteers was 16.81 ± 3.97 degrees during maximum opening and 21.54 ± 2.80 degrees during protrusion; no significant difference compared with the patients. The condyles of the affected side tended to deviate laterally in all patients during mouth opening and protrusion. Patients with condylar reconstruction showed more severe symptoms of mouth opening limitation and mandibular movement deviation as well as shorter chewing cycles than patients with condylar preservation. CONCLUSION: Patients with condylar reconstruction showed flatter movement paths of the condyle points, greater lateral motion range, and shorter chewing cycles than those with condylar preservation. The method of mandibular motion simulation based on intraoral scanning registration was feasible to simulate condylar movement.

[Application of double-layer soft tissue suture closure technique in the surgical treatment of patients with mandible medication-related osteonecrosis of the jaw of early and medium stages].

OBJECTIVE: To investigate the clinical application effect of double-layer soft tissue (DLST) suture closure technique in patients with mandible medication-related osteonecrosis of the jaw (MRONJ) of early and medium stages resulted in application of anti-bone-resorptive drugs. METHODS: Early to medium stage mandible MRONJ patients who underwent surgical treatment in the fourth ward of Peking University School and Hospital of Stomatology from October 2021 to September 2022 were included. Clinical information of the patients were collected, including primary disease, concomitant disease, medication regimen (drug type, duration of medication), MRONJ stage, clinical symptoms, imaging manifestations, etc. During surgery, after using marginal mandibulae resection to remove the necrotic bone, the wound was closed using DLST closure technique. Regular post-operative follow-up was performed to evaluate the therapeutic effect and complications of the DLST technique, the pain score and functional status of the patiens were evaluated. RESULTS: This study totally included 13 patients, 12 women and 1 man, aged (66.69±13.14) years. Seven patients had osteoporosis, 2 had lung cancer, 3 had breast cancer and 1 had prostate cancer among their primary diseases; 7 had no concomitant diseases, 2 had diabetes mellitus, 2 had cardiovascular disease and 1 had dry syndrome. Intravenous zoledronic acid were used in 9 patients, the average duration was (37.7±20.0) months, and other drugs, such as letrozole tablets were taken in 7 patients at the same time; Denosumab injection was used in 3 patients for an average of (10.3±11.9) months; Alendronate sodium tablets were taken in 5 patients for an average of (55.20±27.20) months, and prednisone acetate tablets or acarbose tablets were taken to varying degrees in 2 patients. The average post-operative follow-up was 11.9 months (9 to 17 months), and all the 13 patients were cured without complications, such as pus overflow and so forth. The pre-operative score of Karnofsky performance status (KPS) in the patients was 68.46±14.05, and the post-operative score was 82.31±15.36, and the difference was statistically significant (P < 0.05). The pre-operative score of visual analogue scale (VAS) in the patients was 5.77±0.73 and the post-operative score was 0.38±0.51, and the difference had statistical significance (P < 0.001). CONCLUSION: The double-layer soft tissue suture closure technique can achieve good clinical results in patients with MRONJ of the mandible using anti-bone-resorptive drugs alone, and can provide clinical treatment ideas for MRONJ patients with more complicated drug use.

[Left mandibular osteonecrosis following herpes zoster of the third branch of left trigeminal nerve: A case report].

Herpes zoster of trigeminal nerve was a common skin disease caused by varicella-zoster virus infection. Simple involvement of the third branch of trigeminal nerve was rare, and so were oral complications such as pulpitis, periodontitis, spontaneous tooth loss, bone necrosis, etc. This article presented a case of herpes zoster on the third branch of the left trigeminal nerve complicated with left mandibular osteonecrosis. We reported the case of a 64-year-old man with sudden pain in the left half of the tongue 1 month ago, and then herpes on the left facial skin appeared following with acute pain.The local hospital diagnosed it as herpes zoster and treated it with external medication. A few days later, he developed gum pain in the left mandibular posterior tooth area. He was admitted to Peking University School and Hospital of Stomatology one week ago with loose and dislodged left posterior tooth accompanied by left mandibular bone surface exposure. Clinical examination showed bilateral symmetry and no obvious restriction of mouth opening. Visible herpes zoster pigmentation and scarring on the left side of the face appeared. The left mandibular posterior tooth was missing, the exposed bone surface was about 1.5 cm×0.8 cm, and the surrounding gingiva was red and swollen, painful under pressure, with no discharge of pus. The remaining teeth in the mouth were all Ⅲ degree loosened. Imageological examination showed irregular low-density destruction of the left mandible bone, unclear boundary, and severe resorption of alveolar bone. The patient was diagnosed as left mandibular osteonecrosis. Under general anesthesia, left mandibular lesion exploration and curettage + left mandibular partial resection + adjacent flap transfer repair were performed. The patient was re-exmained 6 months after surgery, there was no redness, swelling or other abnormality in the gums and the herpes pigmentation on the left face was significantly reduced. Unfortunately, the patient had complications of postherpetic neuralgia. This case indicate that clinicians should improve their awareness of jaw necrosis, a serious oral complication of trigeminal zoster, and provide early treatment. After the inflammation was initially controlled, surgical treatment could be considered to remove the necrotic bone, curettage the inflammatory granulation tissue, and extraction of the focal teeth to avoid further deterioration of the disease.

Long-term result of 125 I seed brachytherapy for pediatric desmoid tumor in the head and neck.

BACKGROUND: Desmoid tumor (DT) is rare and challenging, often affects the head and neck (HN) region in children, and its appropriate treatments are under-discussed. This study aimed to retrospectively evaluate the long-term effectiveness and safety of 125 I seed brachytherapy for pediatric DT in HN. PROCEDURE: Seven pediatric patients with a median age of three years who suffered from DT in HN treated with 125 I brachytherapy from January 2008 to June 2018 were included. Among these, five underwent sole brachytherapy and the others combined with surgery under prescription doses ranging from 10,000 to 12,000 cGy. The rate of local control (LC), complete response (CR), and partial response (PR) was calculated after evaluation by radiological and pathological means. Radiation-associated toxicities were also evaluated. RESULTS: The LC rate was 7/7 during the follow-up time ranging from 43 to 135 months and with a mean of 57 months. No recurrent lesion was found in the patients receiving surgery combined with brachytherapy. In patients treated with sole brachytherapy, the radiological PR rate and CR rate were 4/5 and 1/5, respectively. In those reaching radiological PR, 3/4 were pathological CR. Slight acute radiation-associated toxicities were observed in all patients, and no late or severe acute toxicity was observed. CONCLUSION: 125 I brachytherapy is effective and safe in the management of pediatric DT in HN as the sole modality or combined with surgery in the long term.

Bacterial distribution and inflammatory cytokines associated with oral cancer with and without jawbone invasion-a pilot study.

OBJECTIVE: To explore the bacterial and inflammatory variations in oral cancer patients with and without jawbone invasion. MATERIALS AND METHODS: A total of 20 specimens of fresh tumor tissue, including 10 from the tumor-invaded jawbone (JIOC group) and 10 without jawbone invasion (NJIOC group), were collected from oral cancer patients. Meanwhile, 10 specimens from normal oral mucosa were collected from healthy patients (control group). The microbiomic content of each sample was analyzed by 16S rRNA gene sequencing, while the expression of inflammatory cytokines was assessed using protein microarray analysis. RESULTS: There was a significant difference in ß diversity between JIOC and NJIOC groups (P < 0.05), but no difference between NJIOC and control groups. The average relative abundance of Fusobacteria and Spirochaetes was higher, while Firmicutes was lower in the JIOC group than in the NJIOC group (all P < 0.05). The expression of pro-inflammatory cytokines like interleukin (IL)-1α, IL-1ß, IL-4, and IL-8 was upregulated in the JIOC group compared with the NJIOC group, while MCP-1 was decreased (all P < 0.05). Slackia spp. and Howardella spp. were positively correlated with IL-4; Odoribacter spp. and Acidaminococcaceae spp. were negatively correlated with IL-4, and Clostridium XIVa spp. was negatively correlated with IL-1α and IL-1ß. CONCLUSION: Bacterial and inflammatory differences were observed in oral cancer patients with and without jawbone invasion, where the relative abundance of the differential bacteria was associated with the expression of the inflammatory cytokines. CLINICAL RELEVANCE: This study investigated the changes in the flora during jawbone invasion in oral cancer and its effect on inflammatory factors, elucidating the possible mechanisms of jawbone invasion caused by oral cancer, which may lead to new ideas for the clinical prevention and treatment of jawbone invasion in oral cancer.

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.

Endoscopic visualization of the inferior alveolar nerve associated with somatosensory changes after impacted mandibular third molar extraction.

The aim of this study is to assess the relationship between somatosensory functional changes and inferior alveolar nerve (IAN) exposure after impacted mandibular third molars (M3M) removal. We recruited 35 patients who underwent impacted M3M extraction near the IAN. The M3Ms were extracted by combined endoscopy, piezosurgery, and contra-angle high-speed turbine handpiece. All IAN canal perforations and exposed regions were recorded and measured by endoscopy after extraction and on cone-beam computed tomography (CBCT) images before extraction. The patients were followed up 1, 7, and 35 days after surgery. A standardized quantitative sensory testing (QST) battery was performed on the lower lip skin. All of 35 cases had exposed IAN on CBCT images, 5 of which had no exposed IAN under endoscopy. For the other 30 cases, the endoscopy-measured IAN length and width were shorter than the CBCT measurements (P < 0.001). The warm and mechanical detection thresholds (MDT) on the operation side were significantly higher than the contralateral side after surgery (P < 0.05). Thermal sensory limen, MDT, and cold pain threshold were strongly correlated with the exposed IAN length and MDT also with the exposed IAN width one day after surgery. In conclusion, it was found that not all exposed IAN in CBCT images were real exposure after surgery. The intraoperative exposed IAN endoscopic measurements were smaller than by CBCT and strongly correlated with some QST parameters.

Anti-angiogenic drug aggravates the degree of anti-resorptive drug-based medication-related osteonecrosis of the jaw by impairing the proliferation and migration function of gingival fibroblasts.

BACKGROUND: Long-term use of anti-resorptive or anti-angiogenic drugs in cancer patients with odontogenic infections may lead to medication-related osteonecrosis of the jaw (MRONJ). This study investigated whether anti-angiogenic agents aggravate MRONJ occurrence in anti-resorptive-treated patients. METHODS: The clinical stage and jawbone exposure of MRONJ patients caused by different drug regimens were analyzed to ascertain the aggravation effect of anti-angiogenic drugs on anti-resorptive drug-based MRONJ. Next, a periodontitis mice model was established, and tooth extraction was performed after administering anti-resorptive and/or anti-angiogenic drugs; the imaging and histological change of the extraction socket were observed. Moreover, the cell function of gingival fibroblasts was analyzed after the treatment with anti-resorptive and/or anti-angiogenic drugs in order to evaluate their effect on the gingival tissue healing of the extraction socket. RESULTS: Patients treated with anti-angiogenic and anti-resorptive drugs had an advanced clinical stage and a bigger proportion of necrotic jawbone exposure compared to patients treated with anti-resorptive drugs alone. In vivo study further indicated a greater loss of mucosa tissue coverage above the tooth extraction in mice treated with sunitinib (Suti) + zoledronate (Zole) group (7/10) vs. Zole group (3/10) and Suti group (1/10). Micro-computed tomography (CT) and histological data showed that the new bone formation in the extraction socket was lower in Suti + Zole and Zole groups vs. Suti and control groups. In vitro data showed that the anti-angiogenic drugs had a stronger inhibitory ability on the proliferation and migration function of gingival fibroblasts than anti-resorptive drugs, and the inhibitory effect was obviously enhanced after combining zoledronate and sunitinib. CONCLUSION: Our findings provided support for a synergistic contribution of anti-angiogenic drugs to anti-resorptive drugs-based MRONJ. Importantly, the present study revealed that anti-angiogenic drugs alone do not induce severe MRONJ but aggravate the degree of MRONJ via the enhanced inhibitory function of gingival fibroblasts based on anti-resorptive drugs.

Bone morphogenetic protein receptor 1α promotes osteolytic lesion of oral squamous cell carcinoma by SHH-dependent osteoclastogenesis.

Oral squamous cell carcinoma (OSCC) is an aggressive tumor that usually invades the maxilla or mandible. The extent and pattern of mandibular bone invasion caused by OSCC are the most important factors determining the treatment plan and patients' prognosis. Yet, the process of mandibular invasion is not fully understood. The following study explores the molecular mechanism that regulates the mandibular invasion of OSCC by focusing on bone morphogenetic protein receptor 1α (BMPR1α) and Sonic hedgehog (SHH) signals. We found that BMPR1α was positively correlated to bone defect of OSCC patients. Mechanistically, BMPR1α signaling regulated the differentiation and resorption activity of osteoclasts through the interaction of OSCC cells and osteoclast progenitors, and this process was mediated by SHH secreted by tumor cells. The inhibition of SHH protected bone from tumor-induced osteolytic activity. These results provide a potential new treatment strategy for controlling OSCC from invading the jawbones.

Integrated weighted gene coexpression network analysis identifies Frizzled 2 (FZD2) as a key gene in invasive malignant pleomorphic adenoma.

BACKGROUND: Invasive malignant pleomorphic adenoma (IMPA) is a highly malignant neoplasm of the oral salivary glands with a poor prognosis and a considerable risk of recurrence. Many disease-causing genes of IMPA have been identified in recent decades (e.g., P53, PCNA and HMGA2), but many of these genes remain to be explored. Weighted gene coexpression network analysis (WGCNA) is a newly emerged algorithm that can cluster genes and form modules based on similar gene expression patterns. This study constructed a gene coexpression network of IMPA via WGCNA and then carried out multifaceted analysis to identify novel disease-causing genes. METHODS: RNA sequencing (RNA-seq) was performed for 10 pairs of IMPA and normal tissues to acquire the gene expression profiles. Differentially expressed genes (DEGs) were screened out with the cutoff criteria of |log2 Fold change (FC)|> 1 and adjusted p value < 0.05. Then, WGCNA was applied to systematically identify the hidden diagnostic hub genes of IMPA. RESULTS: In this research, a total of 1970 DEGs were screened out in IMPA tissues, including 1056 upregulated DEGs and 914 downregulated DEGs. Functional enrichment analysis was performed for identified DEGs and revealed an enrichment of tumor-associated GO terms and KEGG pathways. We used WGCNA to identify gene module most relevant with the histological grade of IMPA. The gene FZD2 was then recognized as the hub gene of the selected module with the highest module membership (MM) value and intramodule connectivity in protein-protein interaction (PPI) network. According to immunohistochemistry (IHC) staining, the expression level of FZD2 was higher in low-grade IMPA than in high-grade IMPA. CONCLUSION: FZD2 shows an expression dynamic that is negatively correlated with the clinical malignancy of IMPA and it plays a central role in the transcription network of IMPA. Thus, FZD2 serves as a promising histological indicator for the precise prediction of IMPA histological stages.

Lateral Pterygoid Muscle Ossification After Intraoral Condylectomy.

PURPOSE: Lateral pterygoid muscle ossification has not been reported in condylectomy patients. This study aimed to explore the incidence, risk factors, and imaging characteristics of 38 cases with lateral pterygoid muscle ossification among 54 patients after condylectomy via intraoral approach. METHODS: This retrospective study included 54 patients following simultaneous orthognathic surgery and condylectomy with coronoid process resection via intraoral approach. The authors evaluated the preoperative, 1 week, 6 months, and 1 year or more postoperative computed tomographic (CT) scans for the presence of lateral pterygoid muscle ossification and its characteristics. Sex, age at the time of surgery, disease course, affected side, preoperative alkaline phosphatase, pathology diagnosis, the height of the removed condyle, condylar shape, operator, preoperative temporomandibular joint movement, and clinical symptoms were assessed as risk factors for ossification. RESULTS: No incidence of lateral pterygoid muscle ossification was found on preoperative CT images. Various small-size osseous masses were observed in the lateral pterygoid muscles on postoperative 6 months CT images in 38/54 patients (70.37%) after condylectomy. But no apparent enlargement of the osseous masses was found. No patients complained of clinical discomfort or functional disorder during the follow-up period (23.11 ± 13.16 months). No significant risk factors for ossification were found. CONCLUSIONS: Lateral pterygoid muscle ossification is relatively common in patients after condylectomy via intraoral approach. However, its enlargement is self-limited and remains stable 6 months after surgery. it has no adverse effects on the temporomandibular joint functional movement.

Reconstruction of Complete Bilateral Maxillary Defects With Free Flaps.

ABSTRACT: Reconstruction of complete bilateral maxillary defects (CBMDs) can be challenging due to the extensive loss of bone and soft tissues. This is a retrospective case series of 46 consecutive patients with CBMDs that were reconstructed with different micro-vascular free flaps. The authors aimed to evaluate the surgical outcomes and discuss the different reconstruction options in this case series. Thirty-six patients underwent reconstruction following ablation surgery for malignant tumors, 6 for benign tumors, 3 patients were treated for osteomyelitis, and 1 patient underwent free flap reconstruction for posttraumatic defects. Free fibula flap (n = 26) is the most commonly used reconstruction method in this case series, which was used in all defect types. This is followed by anterolateral thigh flap (n = 10), 5 rectus abdominis myocutaneous free flap, 3 radial forearm free flaps, and 2 composite free flaps. In this series, 44 free flaps survived, whereas only 2 flaps were lost. All patients could resume a soft diet postoperatively. Reconstruction of CBMDs with vascularized free flaps is a safe and reliable procedure.

pERK-mediated IL8 secretion can enhance the migration, invasion, and cisplatin resistance of CD10-positive oral cancer cells.

BACKGROUND: Cancer stem cells (CSCs) drive tumor initiation and progression and participate in tumor chemoresistance. We recently discovered that oral squamous cell carcinoma (OSCC) cells that highly express CD10 (CD10H cells) present cancer stem cells (CSC)-associated characteristics, which, in turn, affect the tumor growth, epithelial-mesenchymal transition (EMT), and resistance to cisplatin. In this study, we further investigated this mechanism in vitro and in vivo. We hypothesized that IL8 might regulate migration, invasion, and cisplatin resistance of CD10-positive oral cancer cells through the ERK pathway. METHODS: CD10 MicroBead Kit was used to select HN6 cells with high and low expression of CD10. The target protein IL8 was screened via protein chip assay. Lentiviral transduction and specific inhibitor were applied to investigate the signaling pathway. Real-time PCR, Western blot, and immunohistochemistry were used to analyze the mRNA and protein expression; transwell assay, spheroid formation assay, and cell viability assay were used to study the cell biological behavior in vitro; xenograft animal model was used to evaluate the tumor formation rate in vivo. RESULTS: Overexpression of CD10 promoted CSC-related genes expression and enhanced migration, invasion, spheroid formation, and chemoresistance in HN6 cells. Moreover, the overexpression of IL8 was detected in OSCC tumor tissue and cell lines (HN6 and CAL27) overexpressing CD10. IL8 secreted by CD10H HN6 promoted migration and invasion and restored tumor chemosensitivity via the p-ERK signaling pathway, while the inhibition of IL8 increased the chemosensitivity to cisplatin. CONCLUSIONS: IL8 secretion by CD10 positive cells promotes migration, invasion, and cisplatin resistance of OSCC via the p-ERK signaling pathway.

GPD1L is negatively associated with HIF1α expression and predicts lymph node metastasis in oral and HPV- Oropharyngeal cancer.

OBJECTIVE: The study is to determine if Glycerol-3-phosphate dehydrogenase 1-like (GPD1L) and hypoxia-inducible factor-1α (HIF1α) can identify high-risk patients with delayed lymph node metastasis in early-stage head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: The mRNA and protein expressions of markers were analyzed using fresh and paraffin embedded HNSCC specimens. The statistical analyses included chi-squared test, t test, correlation analysis, and univariate and multivariate analyses. RESULTS: GPD1L (downregulated) and HIF1α (upregulated) mRNA expression had a negative correlation (r = -.496, p = .001) in cT1-2N0 HNSCC. The low GPD1L + high HIF1α expression group (22.6%) showed a significant decrease in disease-free survival compared with the high GPD1L + low HIF1α expression group (71.4%) in the neck dissection group. The low GPD1L + high HIF1α expression (39.4%) resulted in a significantly higher delayed metastasis rate than the high GPD1L + low HIF1α expression (5.6%) for cT1-2N0 HNSCC in the neck observation group. GPD1L and HIF1α protein expression more accurately predicted lymph node metastasis than the WINTER hypoxia gene panel (false-negative rate in predicting metastasis: 8.1% versus 26.4%). Cox regression analyses found that the combined protein expression of GPD1L and HIF1α could predict delayed metastasis (HR:0.118, 95% CI:0.027-0.525). CONCLUSIONS: Low GPD1L + high HIF1α expression can serve as candidate biomarkers for high-risk populations with lymph node metastases in early-stage HNSCC.

Cancer stemness of CD10-positive cells regulated by Hedgehog pathway promotes the resistance to cisplatin in oral squamous cell carcinoma.

OBJECTIVE: To explore the role of CD10 in cisplatin resistance of oral squamous cell carcinoma (OSCC) and its association with the Hedgehog (Hh) signaling pathway and cancer stem cells (CSCs). METHODS: The correlation between cell viability and CD10 expression was analyzed in different OSCC cell lines after the cisplatin treatment. Genes related to chemotherapy resistance, cancer stem cells and the epithelial-mesenchymal transition were detected by quantitative real-time PCR (qPCR) in CD10high and CD10low OSCC cells. Mouse xenograft model and venous metastasis model were used to explore the potential regulatory mechanism of the resistance effect of CD10 on cisplatin. RESULTS: The higher expression of CD10 gene in different cell lines displayed enhanced cisplatin resistance ability. The expression of genes related to chemotherapy resistance, cell stemness, and the epithelial-mesenchymal transition was significantly higher in CD10high cells compared with CD10low cells. Moreover, the combination of cisplatin and Hh pathway inhibitors significantly reduced the resistance of CD10 to cisplatin in the xenograft model and venous metastasis models. CONCLUSION: CD10-positive cells are implicated in developing cisplatin resistance of OSCC, which could be related to its cancer stem cell characteristics regulated by the Hedgehog pathway.

Navigation in bone-impacted premaxillary supernumerary tooth removal: a preliminary clinical trial.

AIM: The present clinical trial aimed to preliminarily assess whether navigation could help to position impacted supernumerary teeth (STs) and reduce surgical trauma. MATERIALS AND METHODS: Subjects with an impacted supernumerary tooth (ST) in the premaxillary area were enrolled in the study and randomly distributed into a navigation group and a control group. In the navigation group, STs were positioned and extracted under real-time optic navigation. In the control group, STs were extracted depending on the surgeon's experience. Subjects were followed up for 12 to 24 weeks postsurgery. Operating time, futile bony trauma, and the positioning precision of the STs were the major outcomes assessed. Multivariate correlation analysis was performed. RESULTS: In 24 subjects, 32 STs were removed and no severe complications occurred in either group. The proportion of ST exposure at the planned access point was 100% in the navigation group and 68.75% in the control group (χ² = 5.926, P = 0.015). Futile length, futile width, and the distance between the point where the ST was initially exposed and the bony point planned for accessing it were related to both navigation/control grouping and bone thickness in the access side. For challenging STs with bone thickness of > 0.5 mm in the access side (N = 22), the futile length in the navigation group (0.0 [0.0, 4.0] mm) was significantly smaller than that in the control group (3.0 [0.0, 8.0] mm, P = 0.028). Similarly, the futile width in the navigation group (0.0 [0.0, 2.0] mm) was significantly smaller than that in the control group (2.0 [0.0, 4.0] mm, P = 0.018). CONCLUSIONS: Navigation helped to position impacted STs precisely and reduced surgical bony trauma to some extent, especially in challenging cases in which the bone in the access side was thicker than 0.5 mm.

Suppression of G6PD induces the expression and bisecting GlcNAc-branched N-glycosylation of E-Cadherin to block epithelial-mesenchymal transition and lymphatic metastasis.

BACKGROUND: As the rate-limit enzyme of the pentose phosphate pathway, glucose-6-phosphate dehydrogenase (G6PD) plays important roles in tumour progression, but the exact mechanism through which G6PD controls cancer metastasis remains unclear. METHODS: G6PD expression in resected oral squamous cell carcinoma (OSCC) samples was analysed by immunohistochemistry. The effects and mechanism of G6PD suppression on OSCC cell lines were measured by transwell assay, wound healing assay, western and lectin blot, mass spectrometer analysis, ChIP-PCR, and luciferase reporter assay. BALB/c-nude mice were used to establish orthotopic xenograft model. RESULTS: G6PD expression in the tumours of 105 OSCC patients was associated with lymphatic metastasis and prognosis. In vitro cellular study suggested that G6PD suppression impaired cell migration, invasion, and epithelial-mesenchymal transition. Furtherly, G6PD knockdown activated the JNK pathway, which then blocked the AKT/GSK-3ß/Snail axis to induce E-Cadherin expression and transcriptionally regulated MGAT3 expression to promote bisecting GlcNAc-branched N-glycosylation of E-Cadherin. An orthotopic xenograft model further confirmed that dehydroepiandrosterone reduced lymphatic metastatic rate of OSCC, which was partially reversed by JNK inhibition. CONCLUSIONS: Suppression of G6PD promoted the expression and bisecting GlcNAc-branched N-glycosylation of E-Cadherin via activating the JNK pathway, which thus acted on OSCC metastasis.