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Lymph node metastasis, the initial step in distant metastasis, represents a primary contributor to mortality in patients diagnosed with oral squamous cell carcinoma (OSCC). However, the underlying mechanisms of lymph node metastasis in OSCC remain incompletely understood. Here, the transcriptomes of 56 383 single cells derived from paired tissues of six OSCC patients are analyzed. This study founds that CXCR4+ epithelial cells, identified as highly malignant disseminated tumor cells (DTCs), exhibited a propensity for lymph node metastasis. Importantly, a distinct subset of tumor-associated macrophages (TAMs) characterized by exclusive expression of phosphoprotein 1 (SPP1) is discovered. These TAMs may remodel the metastatic lymph node microenvironment by potentially activating fibroblasts and promoting T cell exhaustion through SPP1-CD44 and CD155-CD226 ligand-receptor interactions, thereby facilitating colonization and proliferation of disseminated tumor cells. The research advanced the mechanistic understanding of metastatic tumor microenvironment (TME) and provided a foundation for the development of personalized treatments for OSCC patients with metastasis.

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A near-infrared fluorescent probe (TX-P) for detecting peroxynitrite is constructed. The probe has a near-infrared emission (725 nm), large Stokes shift (125 nm) and excellent sensitivity and selectivity. In addition, TX-P can be used to visualize ONOO- in living cells, image ONOO- in paw edema mice and evaluate anti-inflammatory drugs.

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An ultra-sensitive photoelectrochemical (PEC) sensor based on perovskite composite was developed for the determination of alkaline phosphatase (ALP) in human serum. In contrast to CsPbBr3 or Y6 that generated anodic current, the heterojunction of CsPbBr3/Y6 promoted photocarriers to separate and generated cathodic photocurrent. Ascorbic acid (AA) was produced by ALP hydrolyzing L-ascorbic acid 2-phosphate trisodium salt (AAP), which can combine with the holes on the photoelectrode surface, accelerating the transmission of photogenerated carriers, leading to enhanced photocurrent intensity. Thus, the enhancement of PEC current was linked to ALP activity. The PEC sensor exhibits good sensitivity for detection of ALP owing to the unique photoelectric properties of the CsPbBr3/Y6 heterojunction. The detection limit of the sensor was 0.012 U·L-1 with a linear dynamic range of 0.02-2000 U·L-1. Therefore, this PEC sensing platform shows great potential for the development of different PEC sensors.

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BACKGROUND: Previous studies on oral submucous fibrosis (OSF) mostly focused on the activation of fibroblasts and collagen metabolism, while little involved in the epithelium. As we have reported the role of differentiated embryo-chondrocyte expressed gene 1 (DEC1) in oral cancer and other precancerous lesions, this research aimed to explore its role in the OSF epithelium. METHODS: Expression of DEC1 and other proteins were investigated in tissue array constructed with 33 OSF and 14 normal oral mucosa (NOM) tissues. Human oral keratinocytes treated with arecoline and/or hypoxia were used to simulate OSF epithelium and detected for morphological and protein alterations. Inhibition of DEC1 was used to explore its mediating role. Finally, animal models of OSF constructed by locally arecoline injecting in buccal mucosa were used to verify our findings. RESULTS: DEC1 overexpression could be detected in the epithelium of OSF compared with that in NOM followed by phosphorylated FAK and Akt, and DEC1 showed a significant positive correlation with them. Cytology experiment revealed that OSF-like treatment could upregulate DEC1 expression followed by phosphorylated FAK, Akt, but inhibit E-cadherin, while knockdown of DEC1 could suppress the effects. In addition, OSF mice revealed higher expression of DEC1 in the epithelium of buccal mucosa, along with synchronized alterations of phosphorylated FAK and Akt. CONCLUSION: In the epithelium of OSF, overexpression of DEC1 induced activation of FAK/Akt signal axis, caused mesenchymal transition in epithelial cells, and may promote malignant transformation of OSF. Targeting DEC1 in OSF could be promising a new target for the diagnosis and treatment of this process.

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Objective: The traditional lateral arm free flap (tLAFF) has the disadvantages of short vascular pedicle, small vascular diameter, and non-perforator flap. We used a new method to prepare modified LAFF (mLAFF) and evaluate its application value in the repair of oral and maxillofacial soft tissue defects. Methods: The anatomical features of the flap were recorded and compared between the tLAFF group and the mLAFF group. All the flaps in the modified group were perforator flaps. Statistical analysis was performed on the data using ANOVA on SPSS 22.0 statistical software package. Results: Forty-five mLAFFs were prepared as eccentric design rotation repair perforated flap, or multi-lobed or chimeric perforator flaps. Compared with the tLAFF, the vascular pedicle length of the mLAFF was increased, and the outer diameter of the anastomosis was thickened. The damage to the donor site was less. The difference was statistically significant. Conclusion: The mLAFF can effectively lengthen the vascular pedicle length and increase the anastomosis diameter. Perforator LAFFs in the repair of oral and maxillofacial defects have good application value.

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Introduction: It is urgently needed to develop composite bone scaffold with excellent mechanical properties and bioactivity in bone tissue engineering. Combining graphene oxide (GO) and hydroxyapatite (HAP) for the reinforcement of biopolymer bone scaffold has emerged as a promising strategy. However, the dispersion of GO and HAP remains to be a big challenge. Objectives: In this present work, the mechanical properties of GO and the bioactivity of and HAP were combined respectively via in situ synthesis for reinforcing biopolymer bone scaffold. Methods: GO nanosheets were employed to in situ synthesize GO-HAP nanocomposite via hydrothermal reaction, in which their abundant oxygen-containing groups served as anchor sites for the chelation of Ca2+ and then Ca2+ absorbed HPO42- via electrovalent bonding to form homogeneously dispersed HAP nanorods. Thereby, the GO-HAP nanocomposite was blended with biopolymer poly-L-lactic acid (PLLA) for fabricating biopolymer scaffold by selective laser sintering (SLS). Results: GO nanosheets were uniformly decorated with HAP nanorods, which were about 60 nm in length and 5 nm in diameter. The compressive strength and modulus of PLLA/12%GO-HAP were significantly increased by 53.71% and 98.80% compared to the pure PLLA scaffold, respectively, explained on the base of pull out, crack bridging, deflection and pinning mechanisms. Meanwhile, the mineralization experiments indicated the PLLA/GO-HAP scaffold displayed good bioactivity by inducing the formation of apatite layer. Besides, cell culturing experiments demonstrated the favorable cytocompatibility of scaffold by promoting cell adhesion and proliferation. Conclusions: The present findings show the potential of PLLA/GO-HAP composite scaffold via in situ synthesis in bone tissue engineering.

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Proteasome 26S subunit, ATPase 2 (PSMC2) is a recently identified gene which is potentially associated with human carcinogenesis. However, the effects of PSMC2 on oral squamous cell carcinoma (OSCC) is still unclear. Here, we investigated PSMC2 expression in OSCC tissues and explored its effects on the biological behaviors of OSCC cells. PSMC2 expression was evaluated by immunohistochemistry in a tissue microarray containing 60 OSCC tissues and 9 normal tissues. PSMC2 was knocked down through lentivirus infection in OSCC cell lines. MTT, colony formation, flow cytometry, transwell, and scratch assays were performed to detect effects of PSMC2 knockdown on phenotypes of OSCC cells. Human apoptosis antibody array was used to screen potential downstream of PSMC2 in OSCC. Finally, the effects of PSMC2 knockdown on tumor growth were assessed in a tumor xenograft model using BALB/c nude mice. PSMC2 expression was significantly upregulated in OSCC tissues compared with normal tissues and correlated with poor prognosis. PSMC2 knockdown significantly suppressed cell proliferation, migration, but promoted apoptosis of OSCC cells. Additionally, we confirmed that PSMC2 knockdown can increase the expression of pro-apoptotic proteins. Furthermore, we found that PSMC2 knockdown downregulated expression of p100, p-Akt, CDK6, and upregulated of MAPK9. Xenograft experiments revealed that PSMC2 knockdown can suppress OSCC tumor growth and promote apoptosis. This study demonstrated that PSMC2 plays a critical role in OSCC progression through affecting pro-apoptotic protein expression and apoptosis pathways. It indicated that targeting PSMC2 might be a promising strategy for OSCC treatment.

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Background: Knowledge on the role of miR changes in tumor stroma for cancer progression is limited. This study aimed to investigate the role of miR dysregulation in cancer-associated fibroblasts (CAFs) in oral squamous cell carcinoma (OSCC). Methodology: CAF and normal oral fibroblasts (NOFs) were isolated from biopsies of OSCC patients and healthy individuals after informed consent and grown in 3D collagen gels. Total RNA was extracted. Global miR expression was profiled using Illumina version 2 panels. The functional impact of altered miR-204 expression in fibroblasts on their phenotype and molecular profile was investigated using mimics and inhibitors of miR-204. Further, the impact of miR-204 expression in fibroblasts on invasion of adjacent OSCC cells was assessed in 3D-organotypic co-cultures. Results: Unsupervised hierarchical clustering for global miR expression resulted in separate clusters for CAF and NOF. SAM analysis identified differential expression of twelve miRs between CAF and NOF. Modulation of miR-204 expression did not affect fibroblast cell proliferation, but resulted in changes in the motility phenotype, expression of various motility-related molecules, and invasion of the adjacent OSCC cells. 3' UTR miR target reporter assay showed ITGA11 to be a direct target of miR-204. Conclusions: This study identifies differentially expressed miRs in stromal fibroblasts of OSCC lesions compared with normal oral mucosa and it reveals that one of the significantly downregulated miRs in CAF, miR-204, has a tumor-suppressive function through inhibition of fibroblast migration by modulating the expression of several different molecules in addition to directly targeting ITGA11.

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OBJECTIVE: The use of the traditional American Joint Committee on Cancer (AJCC) staging system alone has limitations in predicting the survival of gingiva squamous cell carcinoma (GSCC) patients. We aimed to establish a comprehensive prognostic nomogram with a prognostic value similar to the AJCC system. METHODS: Patients were identified from SEER database. Variables were selected by a backward stepwise selection method in a Cox regression model. A nomogram was used to predict cancer-specific survival rates for 3, 5 and 10 years in patients with GSCC. Several basic features of model validation were used to evaluate the performance of the survival model: consistency index (C-index), receiver operating characteristic (ROC) curve, calibration chart, net weight classification improvement (NRI), comprehensive discriminant improvement (IDI) and decision curve analysis (DCA). RESULTS: Multivariate analyses revealed that age, race, marital status, insurance, AJCC stage, pathology grade and surgery were risk factors for survival. In particular, the C-index, the area under the ROC curve (AUC) and the calibration plots showed good performance of the nomogram. Compared to the AJCC system, NRI and IDI showed that the nomogram has improved performance. Finally, the nomogram's 3-year and 5-year and 10-year DCA curves yield net benefits higher than traditional AJCC, whether training set or a validation set. CONCLUSION: We developed and validated the first GSCC prognosis nomogram, which has a better prognostic value than the separate AJCC staging system. Overall, the nomogram of this study is a valuable tool for clinical practice to consult patients and understand their risk for the next 3, 5 and 10 years.

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Micro-RNAs (miRs) are emerging as important players in carcinogenesis. Their stromal expression has been less investigated in part due to lack of methods to accurately differentiate between tumor compartments. This study aimed to establish a robust method for dual visualization of miR and protein (pan-cytokeratin) by combining chromogen-based in situ hybridization (ISH) and immunohistochemistry (IHC), and to apply it to investigate stromal expression of miR204 as a putative prognostic biomarker in oral squamous cell carcinoma (OSCC). Four different combinations of methods were tested and ImageJ and Aperio ImageScope were used to quantify miR expression. All four dual ISH-IHC methods tested were comparable to single ISH in terms of positive pixel area percentage or integrated optical density of miRs staining. Based on technical simplicity, one of the methods was chosen for further investigation of miR204 on a cohort of human papilloma virus (HPV)-negative primary OSCC (n = 169). MiR204 stromal expression at tumor front predicted recurrence-free survival (p = 0.032) and overall survival (p = 0.036). Multivariate Cox regression further confirmed it as an independent prognostic biomarker in OSCC. This study provides a methodological platform for integrative biomarker studies based on simultaneous detection and quantification of miRs and/or protein and reveals stromal miR204 as a prognostic biomarker in OSCC.

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BACKGROUND: Facial fracture is one of the most common injuries globally. Some types of facial fractures may cause irreversible damage and can be life-threatening. This study aimed to investigate the health burden of facial fractures at the global, regional, and national levels from 1990 to 2017. METHODS: Facial fracture data, including the incidence, prevalence, and years lived with disability (YLDs) from 1990 to 2017, were obtained from the Global Burden of Disease study. We calculated the estimated annual percentage changes (EAPCs) to assess the changes of facial fractures in 195 countries or territories and 21 regions. RESULTS: From 1990 to 2017, the change in cases of facial fracture incidence was 39% globally, while the age-standardized incidence rate showed a downtrend with an EAPC of 0.00. Syria experienced a ten-fold increase in incidence cases with an EAPC of 9.2, and this condition is largely responsible for the global health burden of facial fractures. The prevalence and YLDs showed a similar trend worldwide as the incidence. Additionally, we found that the incidence, prevalence, and YLDs showed a discrepancy among various age groups with a gradual change of proportion over the past 28 years. The age-standardized rates (ASRs) of facial fractures were nearly twice for male than those for female from 1990 to 2017. CONCLUSIONS: EAPC showed a correlation with the ASRs of facial fractures and had no relationship with socio-demographic index. The proportion of children and elderly suffering from facial fractures slightly changed with time. The ratio of facial fractures between males and females was 2:1. These findings suggest that more targeted and specific strategies based on age and gender should be established in various countries and regions.

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Hydroxyapatite (HAP) can endow a biopolymer scaffold with good bioactivity and osteoconductive ability, while the interfacial bonding is fairly weak between HAP and biopolymers. In this study, HAP was in situ generated on poly(l-lactic acid) (PLLA) particles, and then they were used to fabricate a scaffold by selective laser sintering. Detailedly, PLLA particles were first functionalized by dopamine oxide polymerization, which introduced abundance active catechol groups on the particle surface, and subsequently, the catechol groups concentrated Ca2+ ions by chelation in a simulated body fluid solution, and then, Ca2+ ions absorbed PO43- ions through electrostatic interactions for in situ nucleation of HAP. The results indicated that HAP was homogeneously generated on the PLLA particle surface, and HAP and PLLA exhibited good interfacial bonding in the HAP/PLLA scaffolds. Meanwhile, the scaffolds displayed excellent bioactivity by inducing apatite precipitation and provided a good environment for human bone mesenchymal stem cell attachment, proliferation, and osteogenic differentiation. More importantly, the ingrowth of blood vessel and the formation of new bone could be stimulated by the scaffolds in vivo, and the bone volume fraction and bone mineral density increased by 44.44 and 41.73% compared with the pure PLLA scaffolds, respectively. Serum biochemical indexes fell within the normal range, which indicated that there was no harmful effect on the normal functioning of the body after implanting the scaffold.

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BACKGROUND: Although association between oral squamous cell carcinoma (OSCC) with epithelial-mesenchymal transition (EMT) has been demonstrated, we found CD147, one transmembrane protein we previously studied in oral submucous fibrosis, was correlated with E-cadherin, one marker of EMT. Here, we investigated CD147 expression in the different stages of OSCC and assessed its association with epithelial-mesenchymal transition (EMT). MATERIALS AND METHODS: CD147 and E-cadherin expression in tissue microarrays containing 48 OSCC specimens and matched adjacent tissues was analysed using immunohistochemistry. CD147 was overexpressed or knocked down using exogenous cloning vector and RNA interference, respectively, in OSCC cell lines. Cell proliferation and migration were measured using the CCK8 assay and scratch test, respectively. The expression and localization of EMT-associated proteins was analysed by Western blotting and immunofluorescence. RESULTS: CD147 expression in OSCC tissues was significantly higher than that in adjacent tissues and was markedly higher in cancer tissues with metastasis (P < .05). CD147 expression showed significant negative correlation with E-cadherin expression. CD147 overexpression downregulated E-cadherin and inhibited its complex with ß-catenin and then upregulated N-cadherin and vimentin. Additionally, alterations in CD147 protein expression affected proliferation and migration ability in OSCC cells and were related to ß-catenin nuclear translocation. CONCLUSION: CD147 plays an important role in tumorigenesis and metastasis by promoting EMT progression in OSCC. It may be considered as a novel potential diagnostic and therapeutic target for OSCC.

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OBJECTIVE: This study investigated the feasibility and clinical result of radical resection of posterior buccal carcinoma by using the facial nasolabial fold "smile" incision approach. METHODS: From August 2016 to March 2017, 23 patients with posterior buccal carcinoma were included in this study and underwent radical surgery. Upon finishing the cervical lymph node dissection, an arc-shaped incision was made at 1 cm lateral to the ipsilateral angulus oris, extending along the nasolabial fold upward to the inferolateral margin of the nasal alar while downward in direct continuity with the neck dissection incision. RESULTS: Satisfactory exposure and easy resection of the primary tumor with negative surgical margin were achieved in all 23 patients. After 12-22 months of follow-up (16.5 months on average), all patients recovered favorably, and no local recurrence or distant metastasis was observed. Mouth opening was restored to normal in all cases. The scars were hidden in the nasolabial fold, thus named "smile" incision. CONCLUSIONS: For posterior buccal cancer patients, the facial "smile" incision approach can satisfy the need of surgical exposure, facilitate operative performance, and preserve the annular integrity of the lips without affecting the radical tumor ablation, thereby maintaining a favorable mouth opening. With these advantages, the "smile" incision approach is considered worthy of being popularized in clinical application.

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OBJECTIVE: The purpose of this study was to introduce submandibular-facial artery island flaps (S-FAIF), including the perforator flap, and to evaluate their application for intraoral reconstruction in comparison with submental artery perforator flaps (SMAPF). METHODS: Ninety-six patients who underwent intraoral reconstruction using an S-FAIF (n = 34) or SMAPF (n = 62) after cancer resection were recruited in this study. The flap characteristics (viz., pedicle length, flap size, venous drainage pattern, and harvest time), short-term outcomes (viz., flap partial loss, intraoral wound dehiscence, fistula, and wound infection), and long-term morbidity (viz., facial nerve palsy, neck motion restriction, and hair growth) were compared. RESULTS: Nine S-FAIFs were authentic perforator flaps pedicled by level Ⅰ facial artery perforators, while the rest were island flaps based on level Ⅱ facial artery perforators. The survival rates of S-FAIF and SMAPF were both 100 percent. Flap partial loss occurred in two patients in each group. The pedicle length of S-FAIF was shorter than that of SMAPF (p < 0.001). Statistics analysis revealed no significant difference regarding flap size, venous drainage pattern, short-term outcomes, neck motion restriction, or facial nerve palsy between the groups. S-FAIF required less harvest time (p < 0.001) and experienced less hair growth when compared to SMAPF (p = 0.011). CONCLUSIONS: The S-FAIF is a robust and reliable novel flap and on par with SMAPF for reconstruction of small and medium-sized intraoral defects. It is preferred to SMAPF when technical requirements for flap harvest and hair problems are considered. It should be supplemented to the armamentarium for intraoral reconstruction.

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It is critical to develop a fabrication technology for precisely controlling an interconnected porous structure of scaffolds to mimic the native bone microenvironment. In this work, a novel combined process of additive manufacturing (AM) and chemical etching was developed to fabricate graphene oxide/poly(L-lactic acid) (GO/PLLA) scaffolds with multiscale porous structure. Specially, AM was used to fabricate an interconnected porous network with pore sizes of hundreds of microns. And the chemical etching in sodium hydroxide solution constructed pores with several microns or even smaller on scaffolds surface. The degradation period of the scaffolds was adjustable via controlling the size and quantity of pores. Moreover, the scaffolds exhibited surprising bioactivity after chemical etching, which was ascribed to the formed polar groups on scaffolds surfaces. Furthermore, GO improved the mechanical strength of the scaffolds.

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It is well established that crosstalk between cancer-associated fibroblasts (CAFs) and cancer cells plays a critical role in the occurrence and development of oral squamous cell carcinoma (OSCC). The molecular mechanisms underlying such interaction, however, remain far from clear. Accumulating data have indicated that microRNAs involved in tumor microenvironment, particularly in CAFs, contribute to the activation of fibroblasts and metastasis of cancer cells. Here, we showed that miR-148a was downregulated in CAFs compared with normal fibroblasts isolated from clinical OSCC tissue. Investigation of miR-148a function in fibroblasts demonstrated that overexpression of miR-148a in CAFs significantly impaired the migration and invasion of oral carcinoma cells (SCC-25) by directly targeting WNT10B. Taken together, these data suggested that miR-148a might be a novel candidate target for the treatment of OSCC.

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Oral cancer, represented mainly by oral squamous cell carcinoma (OSCC), is the eighth most common type of human cancer worldwide. The number of new OSCC cases is increasing worldwide, especially in the low-income countries, and the prognosis remains poor in spite of recent advances in the diagnostic and therapeutic modalities. MicroRNAs (miRNAs), 18-25 nucleotides long noncoding RNA molecules, have recently gained significant attention as potential regulators and biomarkers for carcinogenesis. Recent data show that several miRNAs are deregulated in OSCC, and they have either a tumor suppressive or an oncogenic role in oral carcinogenesis. This review summarizes current knowledge on the role of miRNAs as tumor promotors or tumor suppressors in OSCC development and discusses their potential value as diagnostic and prognostic markers in OSCC.

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OBJECTIVE: To evaluate the feasibility and outcomes of chimeric deep circumflex iliac artery perforator flap (DCIAPF) applied in the simultaneous reconstruction of the oromandibular defect. METHODS: Six patients underwent simultaneous oromandibular reconstruction using DCIAPF following segmental mandibulectomy in Xiangya Hospital from March 2014 to July 2014. The skin paddle was designed to be centered on the pre-operative perforator mapping. Retrograde dissection was performed through the underlying abdominal wall to raise the skin paddle. The pedicle was isolated from the groin, and the iliac crest was cut. The deep iliac circumflex vessels were dissected until the skin paddle was reached. Finally, the donor site was strictly sutured layer by layer to avoid ventral hernia. RESULTS: The skin paddles ranged from 3.5 cmx5.0 cm to 7.0 cmx 10.0 cm. The length of the bone components was 5.0 cm to 11.0 cm. All donor sites closed primarily without skin grafting. DCIAPF was harvested successfully in five patients, except for one patient whose perforator originated from the superficial iliac circumflex vessels. An additional pair of anastomoses was performed. All iliac flaps survived. However, slight skin-edge necrosis and exfoliation caused by flap thinning occurred in one patient and healed after pruning and dressing change. The heights of all alveolar ridges were significantly restored, and no serious donorsite complication was observed during the three to six months' follow-up. CONCLUSION: DCIAPF is a reconstructive option for mandibular defects because of its adequate bone tissue and rich blood supply. Satisfactory alveolar ridge restoration greatly facilitates future denture retention. DCIAPF also has a great degree of mobility between the skin paddle and the bone component when appliedin composite oromandibular defect reconstruction.

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