CCR7 affects the tumor microenvironment by regulating the activation of naïve CD8+ T cells to promote the proliferation of oral squamous cell carcinoma.

BACKGROUND: Head and neck cancer is the sixth most common malignancy worldwide, and oral squamous cell carcinoma (OSCC) is the most common head and neck cancer, being one of the leading causes of cancer morbidity and mortality worldwide. CC Chemokine receptor 7(CCR7) is a multifunctional G protein-coupled trans-membrane chemokine that affects immune cell chemotaxis, migration, and cancer progression through its interaction with its ligands C-C motif chemokine ligand 19(CCL19) and C-C motif chemokine ligand 21(CCL21). Numerous studies have demonstrated the involvement of CCR7 in the malignant progression of a variety of cancers, reflecting the pro-cancer properties of CCR7. The Cancer Genome Atlas data suggests CCR7 has elevated expression in oral cancer. Specifically, CCR7 expression in tumor microenvironment (TME) may regulate the ability of some immune cells to engage in anti-tumor immune responses. Since CD8+ T cells have become a key immunotherapeutic target, the role of CCR7 in antitumor immune response of naïve CD8+ T cells in TME has not been thoroughly investigated. METHODS: A CCR7 knockout mouse model was constructed, and the mechanism of ccr7 on the regulation of tumor microenvironment by naïve CD8+ T cells was verified under the guidance of single-cell RNA sequencing combined with in vivo animal experiments and in vitro cell experiments. RESULTS: CCR7 is knocked out with impaired tumor growth and altered CD8+ T cell profiles, revealing the importance of this protein in OSCC. CONCLUSIONS: Inhibition of CCR7 enhances CD8+ T cell activation, proliferation, and anti-tumor function, suggesting its potential as a therapeutic target.

Analysis of the effect of CCR7 on the microenvironment of mouse oral squamous cell carcinoma by single-cell RNA sequencing technology.

BACKGROUND: Studies have shown that CCR7, an important inflammatory factor, can promote the proliferation and metastasis of oral squamous cell carcinoma (OSCC), but its role in the tumor microenvironment (TME) remains unclear. This paper explores the role of CCR7 in the TME of OSCC. METHODS: In this work, we constructed CCR7 gene knockout mice and OSCC mouse models. Single-cell RNA sequencing (scRNA-seq) and bioinformatics were used to analyze the differences in the OSCC microenvironment between three CCR7 gene knockout mice (KO) and three wild-type mice (WT). Immunohistochemistry, immunofluorescence staining, and flow cytometry were used to analyze the expression of key genes in significantly different cell types between the KO and WT groups. An in vitro experiment was used to verify the effect of CCR7 on M2 macrophage polarization. RESULTS: In the mouse OSCC models, the tumor growth rate in the KO group was significantly lower than that in the WT group. Eight main cell types (including tumor cells, fibroblasts, macrophages, granulocytes, T cells, endothelial cells, monocytes, and B cells) were identified by Seurat analysis. The scRNA-seq results showed that the proportion of tumor cells was lower, but the proportion of inflammatory cells was significantly higher in the KO group than in the WT group. CellPhoneDB analysis results indicated a strong interaction relationship between tumor cells and macrophages, T cells, fibroblasts, and endothelial cells. Functional enrichment results indicated that the expression level of the Dusp1 gene in the KO group was generally higher than that in the WT group in various cell types. Macrophage subclustering results indicated that the proportion of M2 macrophages in the KO group was lower than that in the WT group. In vitro experimental results showed that CCR7 can promote M2 macrophage polarization, thus promoting the proliferation, invasion and migration of OSCC cells. CONCLUSIONS: CCR7 gene knockout can significantly inhibit the growth of mouse oral squamous cell carcinoma by promoting the polarization of M2 macrophages.

Radial and ulnar forearm free flaps: A critical comparison of donor site morbidity and its impact on quality of life.

BACKGROUND: A poor evidence basis exists regarding direct comparing objective and subjective donor site morbidity associated with forearm flap. The authors evaluated the postoperative donor-site complications and quality of life outcomes between radial forearm free flap (RFFF) and ulnar forearm free flap (UFFF). METHODS: All patients undergoing RFFF or UFFF harvest were included. Grip strength, pinch strength, wrist range of movement, and testing skin sensitivity were assessed with the appropriate scales at different time intervals. In addition, cosmetic and quality of life were assessed using the Patient and Observer Scar Assessment Scale (POSAS) and Disability of Arm, Shoulder, and Hand (DASH) score. RESULTS: Eighty patients were enrolled (40 RFFF and 40 UFFF). The results showed a short-term reduction in grip strength, fine motor skills (tip pinch, key pinch, palmar pinch), and range of motion was observed for RFFF and improved over time. None of the patients in either group experienced functional disturbance in grip strength, wrist motion, fine motor skills, or sensation to light touch at 1 year. Nine patients experienced partial skin graft loss (RFFF = 6; UFFF = 3). There was a significantly higher incidence of temporary numbness in the RFFF group (p=0.040). Persistent numbness occurred in 3 cases in RFFF. Cold intolerance was significantly lower in UFFF (2.5 %) than in RFFF (22.5%). Moreover, the mean POSAS and DASH score reduced at 12 months compared to 6 months, significantly superior for UFFF. CONCLUSION: Objective function limitations are reversible short-term effects after forearm flap and do not affect daily routines in the long term. Additionally, UFFF appears to be preferred over RFFF for subjective outcomes, which emphasizes the UFFF should be considered an alternative to RFFF for reconstructing soft-tissue defects.

Reconstruction of large defects of anterior floor of mouth with free flaps using a novel individualized flap design method.

The purpose of this study was to introduce a novel individualized flap design method for large anterior floor of the mouth (AFOM) defect reconstruction, review experience with the use of this flap design method for large AFOM defect reconstruction, and assess its functional results. A retrospective study of patients who received large AFOM defect reconstruction with free flaps was conducted. There was a cohort of patients who were treated using the novel individualized flap design method and a cohort without flap design. Functional outcomes were evaluated with appropriate scales. Outcomes were analyzed, and a p-value <0.05 was considered significant. 22 patients received the individualized flap design, while 21 patients were treated without a special flap design. All flaps survived. All free flaps harvested with the novel individualized flap design method better matched AFOM defects. Relative to patients without flap design, patients in the novel individualized flap design group showed significant improvement in speech intelligibility (p = 0.036) and swallowing function (p = 0.019). Within the limitation of the study it seems that large AFOM defect reconstruction with the novel individualized flap design method can not only cover and close the wound to avoid oral-neck fistulae, but also maintains tongue mobility to achieve better functional outcomes than in patients without flap design.

A novel flap design technique for subtotal tongue reconstruction with an "Individualized and Convenient Tongue Model".

BACKGROUND: To achieve improved functional outcomes in subtotal tongue reconstruction, a flap design with sufficient volume and appropriate shape is necessary. In this study, we introduce an "Individualized and Convenient Tongue Model" (ICTM) for flap design in subtotal tongue reconstruction. METHODS: By studying the anatomical morphology of the tongue, we found a similar geometry within the dorsum and body of the tongue as well as the mouth floor. This can be used to create an ICTM through folding and splicing. We can simulate tongue defects in the ICTM and transform defect shapes into guide plates for flap design. In this study, fifty-eight patients requiring subtotal tongue reconstruction were randomly divided into two groups: an ICTM group (35 patients) and a conventional group (31 patients). In the ICTM group, we individually designed profunda artery perforator flaps (PAPFs) or anterolateral thigh flaps (ALTFs) using the ICTM method. In the conventional group, the flap was designed according to the surgeon's clinical experience. Patient demographics, operative and follow-up data were recorded. Swallowing, speech intelligibility, and cosmetic results were assessed using appropriate scales. RESULTS: All flaps survived, although there were no significant differences in tumor size, operation time, flap size, and complication rate compared to the conventional group. Patients in the ICTM group had significantly improved speech intelligibility (p = 0.019), cosmetic appearance (p = 0.009), and swallowing ability (p = 0.003). CONCLUSIONS: The ICTM technique is an effective and convenient solution for subtotal tongue reconstruction that provides an individualized flap design and improves functional outcomes compared to the conventional design.

Donor-site morbidity of free fibula flap in pediatric patients: A systematic review and meta-analysis.

The morbidity of free fibula flap (FFF) in pediatric patients has gained attention. Thus, we aimed to evaluate donor-site morbidity after FFF harvesting in pediatric patients and its relationship with age. A systematic literature search of databases for cross-sectional studies related to pediatric donor-site morbidity after FFF harvesting was performed. Two independent reviewers evaluated relevant article titles and abstracts to extract data regarding donor-site morbidity from each article. Fifteen studies were included in the meta-analysis that evaluated the rate of complications. Individual cases of ankle instability were divided into the 0-13- and 13-17-year-old groups. The Chi-square test was used to compare ankle instability between both groups. A logistic regression model was created to analyze the relationships between age and ankle instability/claw toe. Sixteen English articles published between 2007 and 2021 were included in the systematic review. Information on morbidities of 294 cases in which FFF was used was collected. The mean incidence rate of complications, instability, claw toe, and nerve injury were 19.3%, 12.9%, 5.9%, and 5.1%, respectively. Bivariate analysis showed that age was significantly correlated with the incidence of ankle instability but not with the incidence of claw toe. The Chi-square test showed that the incidence rate of ankle instability between the age groups was significantly different. Therefore, we recommend 14 years of age as a new predictive factor for ankle instability. Nevertheless, there is limited evidence in this field, and more pediatric research is needed to clarify these findings.

Lower lip reconstruction using McGregor fan technique with or without depressor anguli oris chimeric flap. Is there a difference in function and aesthetic outcomes?

BACKGROUND: Lower lip reconstruction aims to maintain facial subunit function and aesthetics. We present a minor modification of the McGregor flap technique, in which depressor anguli oris (DAO) muscle is separately elevated as a chimeric flap together to investigate the outcomes for reconstructing lower lip defects using various functional parameters. METHODS: The study included patients who underwent surgical repair of lower lip defects using a McGregor fan flap with or without DAO muscle chimeric flap between January 2018 and May 2021. The patients were divided into our modified technique with DAO chimeric flap (study group) and conventional McGregor (control group). The primary outcomes were functional evaluation of oral competency, speech intelligibility, and tactile sensation of reconstructed lip outcomes. The functional satisfaction and Patient and Observer Scar Assessment Scale (POSAS) were analyzed. RESULTS: A total of 20 patients were enrolled (10 patients for each group). Excellent oral competence was present in 12 patients, favorably significant in patients with DAO chimeric flap (n = 8/10, p = 0.018). All patients had intelligible speech with insignificant differences between the two groups. No patients demonstrated differences to light touch from baseline sensation at 1 year. Patients in the study group reported more lip function satisfaction (p = 0.049). The POSAS score indicates satisfaction with the appearance of all patients. CONCLUSION: McGregor fan technique combined with DAO muscle chimeric flap offers a good choice by maintaining sensory and motor functions. Our minor modification can ensure the integrity of the oral sphincter, leading to improved lower lip function.

Improving masticatory and swallowing ability of postoperative oral and maxillofacial tumor patients by telerehabilitation-A randomized controlled trial.

OBJECTIVE: To evaluate the effect of telerehabilitation on oral function of oral and maxillofacial tumor patients. DESIGN: Unicentral, single-blind, randomized controlled trial. SETTING: Community. SUBJECTS: Patients with primary oral and maxillofacial tumor receiving surgical treatment. INTERVENTIONS: Telerehabilitation guidance from therapists. MAIN MEASURES: At the beginning of training (T0) and 1 month (T1), 3 months (T2) and 6 months (T3) after training, patients' masticatory ability (mastication efficiency-masticatory performance evaluating gum, maximum bite force and mouth opening) and swallowing ability (water swallowing test) was measured. Modified Sato questionnaire and MD Anderson dysphagia inventory (MDADI) were used for self-evaluation of masticatory and swallowing ability. RESULTS: A total of 64 participants (intervention: 33; control: 31) were included. The masticatory efficiency scores of the intervention group were significantly better than those of the control group at T2 (intervention: 3.67 (0.48); control: 3.03 (0.85)) and T3 (intervention: 4.20 (0.30); control: 3.50 (0.79)); and maximum mouth opening was better at T2 (intervention: 3.18 (0.59); control: 2.77 (0.54)) and T3 (intervention: 3.54 (0.58); control: 3.09 (0.41)). In water swallowing test, the intervention group had better scores at T2 and T3. The scores of MDADI scale in intervention group were better than those in the control group after 3 months of training. In subgroup analysis, the intervention group of oral cancer patients had better swallowing function at T2 and T3, but no significant difference was found in the subgroup of oropharyngeal cancer. CONCLUSIONS: Telerehabilitation could greatly improve the long-term (3-6 months) training effect under the condition of greatly saving medical resources and reducing personnel contact.

Influence of inflammation on bleeding and wound healing following surgical extraction of impacted lower third molars.

OBJECTIVE: This study aimed to investigate the effect of inflammatory states following impacted lower third molar (ILTM) surgery regarding postoperative bleeding and wound healing. METHODS: The study included patients who underwent extraction of ILTMs associated with or without inflammatory conditions. Post-extraction bleeding and wound healing were assessed. In addition, mean grey values (MGVs) of alveolar bone and bone height using an orthopantomography radiograph were analyzed. RESULTS: A total of 376 patients were enrolled; 171 pericoronitis, 51 pulpitis, 44 chronic periapical periodontitis, 36 chronic periodontitis, and 74 control. The bleeding score in the control group was significantly lower than in the periapical periodontitis and periodontitis groups. Excellent wound healing for control, pericoronitis, pulpitis, periapical periodontitis, and periodontitis groups was (78.38%, 35.67%, 70.59%, 70.45%, and 33.33%, respectively). Patients with pericoronitis and periodontitis had significantly poorer wound healing (P < 0.01). The MGV in periapical periodontitis and periodontitis was considerably lower than in the control group. CONCLUSIONS: The inflammatory conditions associated with ILTMs increase the risk of bleeding. So suturing with the placement of local hemostatic agents over a pressure pack alone is recommended. The poorest wound healing was in localized gingival inflammation. Furthermore, MGV was affected by age and was lower with periapical periodontitis.

CC chemokine receptor 7 promotes macrophage recruitment and induces M2-polarization through CC chemokine ligand 19&21 in oral squamous cell carcinoma.

PURPOSE: This study aimed to investigate the impact of CC chemokine receptor 7 (CCR7) on the recruitment and polarization of tumor-associated macrophages (TAMs) in oral squamous cell carcinoma (OSCC). METHODS: We analyzed CCR7 expression pattern, clinicopathological significance, and its association with M2 macrophage infiltration in OSCC by bioinformatic methods. Small interfering RNA (siRNA) was utilized to silence CCR7 in OSCC cells. Conditioned media (CM) was harvested from transfected OSCC cells to establish a co-culture model of THP-1 derived macrophages and OSCC cells. Transwell assay and cell adhesion assay were performed to examine the effect of CCR7 on macrophages recruitment and adhesion. Cytoskeleton was labelled by phalloidin to observe macrophage morphological changes. Moreover, phenotypic alteration of macrophages was measured using quantitative real-time PCR (qRT-PCR), flow cytometry, and immunofluorescence (IF) staining. Ultimately, recombinant human CCL19 and CCL21 were added into the medium of THP-1 derived macrophages to explore their effects on polarization in vitro. RESULTS: In OSCC patients, the overexpression of CCR7 positively correlated with lymph node metastasis and M2 macrophage infiltration. Macrophage not only exhibited enhanced migration, invasion and adhesion abilities, but also appeared more spindle and branched in vitro when treated with CM from OSCC cells. However, these phenomena were abrogated with knockdown of CCR7. We also discovered that inhibition of CCR7 in OSCC cells suppressed TAMs polarization to an M2 phenotype. In addition, recombinant human CCL19 and CCL21 promoted macrophage M2-polarization in vitro. CONCLUSION: CCR7 in OSCC cells promoted recruitment and M2-polarization of THP-1 derived macrophages in vitro by regulating production of CCL19 and CCL21.

Functional and biomechanical assessment of the hand following ulnar forearm free flap transfer: Prospective self-controlled study.

BACKGROUND: There is a shortage of well-designed self-controlled studies evaluating hand biomechanics following ulnar forearm flap (UFF) harvest. This study was conducted to evaluate objective and subjective functional outcomes of the donor's hand following UFF harvest. METHODS: All patients undergoing UFF were included for analysis. Grip strength, wrist movement, forearm supination and pronation, pinch strengths, sensation to light touch and temperature, and hand dexterity were assessed preoperatively and at 1, 3, and 6 months postoperatively. In addition, DASH score (disabilities of the arm, shoulder, and hand score) and Patient and Observer Scar Assessment Scale (POSAS) were analyzed. RESULTS: A total of 18 patients were enrolled. A significant reduction in grip strength for donor's hand was observed between preoperative and postoperative 1 and 3 months (mean difference = 14 kg, 7.38 kg, respectively, p = 0.000 for all). A similar trend was observed for pinch strength and range of motion (p < 0.05). Three months after surgery, there is still a significant reduction in tip pinch, tripod pinch, wrist extension, and supination. All biomechanics outcomes returned to preoperative baseline at 6 months after surgery. No patients suffered significant changes in sensation to light touch, temperature, and numbness by 6 months. There was a significant increase in DASH score by 3.37 points 6 months after operation (p = 0.000). The POSAS score indicates satisfaction with the appearance of the donor site. CONCLUSIONS: UFF is a safe and reliable option for oral cavity reconstruction with minimum donor site morbidities, mainly when cosmesis is paramount. Furthermore, objective hand biomechanics ultimately returns to its preoperative state within 6 months after surgery.

The Overexpression of Fibronectin 1 Promotes Cancer Progression and Associated with M2 Macrophages Polarization in Head and Neck Squamous Cell Carcinoma Patients.

Purpose: This study aimed to investigate the biological roles of fibronectin 1 (FN1) in head and neck squamous cell carcinoma (HNSCC) and its effects on macrophage M2 polarization. Methods: We analyzed FN1 expression pattern and examined its clinical relevance in HNSCC progression by bioinformatic analysis. Small interfering RNA (siRNA) was utilized to silence FN1 in HNSCC cells. Cell counting kit-8 (CCK-8) assay, colony formation assay, Transwell assay and wound healing assay were performed to reveal the effect of FN1 on malignant behaviors of HNSCC cells. Moreover, a co-culture model of macrophages and HNSCC cells was established to investigate whether FN1 induce macrophage M2 polarization. Finally, we used bioinformatic methods to explore the possible FN1-related pathways in HNSCC. Results: FN1 is significantly overexpressed in HNSCC patients and has been obviously correlated with higher pathological stage and poor prognosis. Downregulation of FN1 suppressed the proliferation, migration and invasion of HNSCC cells, and inhibited macrophage M2 polarization in vitro. In addition, "PI3K-Akt" and "MAPK" signaling pathways may be involved in the malignant process of FN1 in HNSCC. Conclusion: The overexpression of FN1 promotes HNSCC progression and induces macrophages M2 polarization. FN1 may serve as a promising prognostic biomarker and therapeutic target in HNSCC.

Superficial parotidectomy with or without great auricular nerve preservation. Is there a difference in postoperative sensory recovery rates and quality of life?

The clinical implications of great auricular nerve (GAN) preservation or sacrifice during parotid surgery have long been a topic of controversy. This study aimed to compare sensory recovery rates and quality of life (QoL) in patients who had undergone superficial parotidectomy and had their GAN preserved or sacrificed. Fifty patients were prospectively analysed, 28 with the GAN preserved, and 22 with it sacrificed. The primary outcomes were tactile sensitivity and QoL. The secondary outcomes were operating times and other complications. There was a gradual improvement in tactile sensitivity in both groups, which showed a statistically significant difference favouring the preserved group at 1, 3, 6, and 9 months postoperatively (p<0.05). There was no statistically significant difference in tactile sensation for both groups at 12 months postoperatively. The overall sensory recovery rates in the GAN preserved and sacrificed groups after 1, 3 ,6, 9 and 12 months were 42.8%, 42.8%, 57.1%, 57.1%, and 78.5%, and 0%, 0%, 13.6%, 27.3%, and 59.1%, respectively. According to the QoL assessment, there was a significant difference in mean (SD) loss of sensation scores (sacrificed group 0.86 (0.94) and preserved group 0.39 (0.62), p= 0.039). However, there were no statistical differences between the groups regarding other categories of the questionnaire. No significant difference was seen between groups regarding operating time and other complications. This study concluded that when evaluated objectively, sensory impairment ultimately lessened in severity in the second half of the first postoperative year. GAN preservation minimised sensation disturbance in long-term results, but overall QoL seemed to be unaffected following GAN preservation or sacrifice.

The prevalence of extra-salivary gland complications in immunoglobulin G4-related sialadenitis.

OBJECTIVES: To estimate the prevalence of extra-glandular lesions in patients with immunoglobulin G4-related sialadenitis (IgG4-RS). METHODS: Six electronic databases (PubMed, EMBASE, Science Direct, Scopus, Web of Science, and China National Knowledge Infrastructure) were systematically searched from the date of inception of each database to March 2021. The Strengthening the Reporting of Observational Studies in Epidemiology statement was used to conduct methodological quality assessment, and a random-effect meta-analysis model was applied to estimate the prevalence. Publication bias was visually assessed using a funnel plot and calculated via Begg's and Egger's tests. The Stata 15 software was used to perform data analysis. RESULTS: A total of 43 articles comprising 1,864 patients with IgG4-RS were considered to be eligible for this study. The pooled prevalence of extra-salivary gland lesions in IgG4-RS was 76.53% with a confidence interval (CI) of (69.39%, 83.04%). A higher prevalence was associated with studies published before or during 2015 (84.38%, CI [74.23%, 92.58%]) than those published after 2015 (68.55%, CI [58.44%, 77.88%]). Lacrimal gland involvement (54.68%, CI [45.61%, 63.60%]) and lymph node swelling (56.96%, CI [48.16%, 65.56%]) were the most frequent lesions. CONCLUSIONS: Extra-glandular lesions were common in patients with IgG4-RS. More high-quality prospective studies with less heterogeneity are required to determine the accurate prevalence.

Overexpression of DOCK6 in oral squamous cell cancer promotes cellular migration and invasion and is associated with poor prognosis.

OBJECTIVE: We aimed to identify the role of DOCK6 in oral squamous cell cancer (OSCC) in this study. DESIGN: DOCK6 expression in OSCC was analyzed using TCGA and GEO datasets and was verified by quantitative real-time PCR, Western blotting, and immunohistochemistry. Statistical analyses were performed to evaluate the relationships between DOCK6 expression and the clinicopathological characteristics of OSCC patients. Wound healing and Transwell assays were performed to assess OSCC cell migration and invasion, respectively. STRING and GO analyses and gene set enrichment analysis were used to identify DOCK6-interacting proteins, their functions and their potential pathways. RESULTS: DOCK6 was significantly upregulated at both the mRNA and protein levels in OSCC tissues (all P < 0.05). DOCK6 levels were positively correlated with age (P < 0.05), lymph node metastasis status (P < 0.001), clinical stage (P < 0.001), differentiation (P < 0.05), and poor clinical outcome (P < 0.05) in OSCC patients. Furthermore, univariate and multivariate analyses revealed that high DOCK6 expression (P < 0.01) and clinical stage III-IV (P < 0.05) might serve as independent prognostic factors for OSCC patients. Functionally, DOCK6 silencing significantly suppressed OSCC cell migration and invasion (all P < 0.05). Ten proteins that interact with DOCK6, more than ten functions related to cancer, and more than six pathways related to DOCK6 in OSCC were identified via bioinformatic methods. CONCLUSION: DOCK6 is upregulated in OSCC, is associated with a poor prognosis in OSCC patients and increases OSCC cells migration and invasion. These findings suggest that DOCK6 may be a potential therapeutic target with prognostic implication in patients with OSCC.

Specificity protein 1/microRNA-92b forms a feedback loop promoting the migration and invasion of head and neck squamous cell carcinoma.

In this study we report a novel specificity protein 1 (SP1)/microRNA-92b (miR-92b) feedback loop regulating the migration and invasion of head and neck squamous cell carcinoma (HNSCC). Microarray and real-time Polymerase Chain Reaction (PCR) were used to detect gene expression in HNSCC tissues and cell lines. Transwell migration, invasion, wound healing and cell counting kit - 8 (CCK-8) cell assays were used to compare cell migration, invasion and proliferation abilities. Chromatin Immunoprecipitation (ChIP) assays were used to detect SP1 binding to the miR-92b promoter. Western blot was used to detect protein levels. An in vivo tumorigenesis experiment was used to evaluate the effect of SP1 knockdown on tumor growth and protein levels were evaluated by immunohistochemistry. We found that the miR-92b expression level was elevated in HNSCC primary focus tissue compared with adjacent normal tissue, and a higher level of miR-92b was related to a higher clinical stage and worse prognosis of HNSCC patients. MiR-92b and SP1 mutually promoted each expression and cooperatively facilitated the migration, invasion and proliferation of HNSCC cells. A decreased level of SP1/miR-92b resulted in a restraint of in vivo tumor growth. In conclusion, our results suggest that the SP1/miR-92b feedback loop generally promotes HNSCC invasion and metastasis, thus presenting a possible therapeutic target in the treatment of HNSCC patients.

DOCK8 Serves as a Prognostic Biomarker and Is Related to Immune Infiltration in Patients With HPV Positive Head and Neck Squamous Cell Carcinoma.

PURPOSE: Dedicator of cytokinesis 8 (DOCK8) was reported to have a vital link to immunoregulation. However, the mechanisms by which it drives immune infiltration in cancer remain uncertain. We tried to assess the role of DOCK8 in patients with cancer, especially human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC). METHODS: Data on the expression and survival of DOCK8 in patients with various cancers were analyzed using the Oncomine and TIMER databases. The TIMER database assessed the relationship of DOCK8 with immune infiltration levels and various markers of multiple immune cells. Gene set enrichment analysis revealed tumor-associated biological processes related to DOCK8. ENCODE database was used to explore relevant transcription factors of DOCK8, and a PPI network was constructed using GENEMINIA. The expression and survival role of DOCK8 was confirmed in patients from independent GEO datasets. RESULTS: We determined that DOCK8 expression was upregulated or downregulated in various cancers unlike in healthy tissues. A high expression of DOCK8 was significantly correlated with a favorable prognosis in HPV-positive HNSCC and lung adenocarcinoma (LUAD). Furthermore, multivariate Cox regression analysis revealed that DOCK8 was an independent prognostic factor of HPV-positive HNSCC. Additionally, elevated DOCK8 expression was positively correlated with multiple immune cell infiltration levels and immune marker expression associated with particular immune cell subsets. Also, 14 pathways involved in immune activities and carcinogenesis, 22 potential TFs, and co-expression proteins of DOCK8 indicated DOCK8 to be related to tumor-associated biological processes. Ultimately, we verified that DOCK8 is upregulated and confers a favorable overall survival and progression-free survival status in patients with HPV-positive HNSCC. CONCLUSION: These results elucidate that high expression of DOCK8 indicates a favorable prognosis in patients with HPV-positive HNSCC as well as increased microenvironmental immune infiltration levels. It would provide new insights into the prognosis predicting and clinical regimen decision making in patients with HPV-positive HNSCC.

Simvastatin inhibits oral squamous cell carcinoma by targeting TMEM16A Ca2+-activated chloride channel.

PURPOSE: Ca2+-activated chloride channel TMEM16A has been found to be overexpressed in many cancers including head and neck squamous cell carcinoma (HNSCC). Nevertheless, the role of TMEM16A in oral squamous cell carcinoma (OSCC) remains unclear. Although simvastatin is known to produce anti-tumor effect, the mechanisms by which simvastatin inhibits cancer remain unclear. METHODS: In this study, we explored the role of TMEM16A expression in human OSCC tissues using both TCGA dataset and immunohistochemistry. CCK-8 assay was applied to evaluate cell proliferation. Patch clamp technique was applied to record TMEM16A Cl- currents. RESULTS: We found that high TMEM16A expression is related with large tumor size, lymph node metastasis, and poor clinical outcome in patients with OSCC. In addition, TMEM16A overexpression could promote cell proliferation, and inhibition of TMEM16A channel activities could suppress cell proliferation in OSCC cells. Furthermore, simvastatin could suppress TMEM16A channel activities, and inhibited cell proliferation in OSCC cells via TMEM16A. CONCLUSION: Our findings identify a novel anti-tumor mechanism of simvastatin by targeting TMEM16A. Simvastatin may represent an innovative strategy for treating OSCC with high TMEM16A expression.

Acellular dermal matrix for prevention of Frey's syndrome after superficial parotidectomy of benign tumors.

PURPOSE: To evaluate: 1) the efficacy of acellular dermal matrix (ADM) to prevent Frey's syndrome (FS) after superficial parotidectomy of benign tumors. 2) the effect of different follow-up intervals on the incidence of FS. METHODS: Fifty-five patients with benign parotid gland tumors underwent superficial parotidectomy were divided into two groups: Non-ADM group (n = 31, 56.3%) and ADM group (n = 24, 43.6%). The primary outcomes measure was the incidence of FS. The secondary outcomes were surgical site depression, infection, salivary sialocele, and salivary fistula. Subjective FS was evaluated using a clinical questionnaire submitted via WeChat at 3, 6, 12, 18, 24, and 32 months postoperatively. Objective FS was evaluated using Minor starch-iodine test at 6 and 12 months postoperatively. RESULTS: There was a statistically significant difference in the incidence of subjective and objective FS when ADM compared with Non-ADM groups (P<0.05). The respective incidence of subjective FS at 3, 6, 12, 18, 24, and 32 months was 4.2%, 8.3%,20.8%, 20.8%, 20.8%, 20.8% in ADM group and 3.2%, 9.7%, 29%, 38.7%, 45.2% in Non-ADM group. The incidence of objective FS after 6 and 12 months was 4.2%, 8.3% in ADM group and 8.3% (2/24), 38.7% (12/31) in Non-ADM group respectively. Five patients in ADM group and 1 patient in Non-ADM group developed sialocele, and all patients resolved with conservative management. Surgical site depression was significantly higher in the Non-ADM group (15/31) compared with (5/24) in ADM (P=0.049). No cases of immune rejection, infection, hematoma, or salivary fistula were observed in ADM group. CONCLUSIONS: The current study demonstrated that 1) ADM could reduce the incidence of FS in the patients undergoing superficial parotidectomy. 2) the peak onset of about 18 months appear to be acceptable follow-up for the development of FS.

Digital navigation and 3D model technology in mandibular reconstruction with fibular free flap: A comparative study.

OBJECTIVE: The low accuracy limits the use of fibular free flap (FFF). We apply digital navigation and 3D printing model technology in mandibular reconstruction to improve FFF's accuracy. METHODS: 34 patients who underwent with FFF to repair mandibular defects were divided into Navigation Group (13 cases, using digital navigation and 3D printing model) and Control Group (21 cases, only 3D printing model). We retrospectively reviewed patients' hospitalization information and evaluated patients by subjective and objective items, such as UW-Qol scale, CT data. RESULTS: The operation time of Navigation Group was higher significantly than Control Group (10.36 ± 1.87vs9.00 ± 1.34 h).There were no significant differences in early postoperative complications. The Qol score of appearance, motion, anxiety were higher significantly in Navigation Group. The CT results showed that mandibular angle deviation and chin deflection of Navigation Group were better significantly than Control Group (1.72 ± 1.29° vs 3.69 ± 1.67°, 2.45 ± 1.39 vs 5.19 ± 2.13 mm). CONCLUSIONS: The digital navigation can improve FFF's accuracy in mandibular reconstruction. It doesn't significantly increase complications. The digital navigation's installation and operation methods should be simplified to shorter operation time and expand its application.