B7-H3 suppresses CD8+ T cell immunologic function through reprogramming glycolytic metabolism.

Malignant neoplasms pose a formidable threat to human well-being. Prior studies have documented the extensive expression of B7 homolog 3 (B7-H3 or CD276) across various tumors, affecting glucose metabolism. Yet, the link between metabolic modulation and immune responses remains largely unexplored. Our study reveals a significant association between B7-H3 expression and advanced tumor stages, lymph node metastasis, and tumor location in oral squamous cell carcinoma (OSCC). We further elucidate B7-H3's role in mediating glucose competition between cancer cells and CD8+ T cells. Through co-culturing tumor cells with flow cytometry-sorted CD8+ T cells, we measured glucose uptake and lactate secretion in both cell types. Additionally, we assessed interferon-gamma (IFN-γ) release and the immune and exhaustion status of CD8+ T cells. Our findings indicate that B7-H3 enhances glycolysis in OSCC and malignant melanoma, while simultaneously inhibiting CD8+ T cell glycolysis. Silencing B7-H3 led to increased IFN-γ secretion in co-cultures, highlighting its significant role in modulating CD8+ T cell functions within the tumor microenvironment and its impact on tumorigenicity. We also demonstrate that glycolysis inhibition can be mitigated by exogenous glucose supplementation. Mechanistically, our study suggests B7-H3's influence on metabolism might be mediated through the phosphoinositide3-kinase (PI3K)/ protein kinase B (Akt)/ mammalian target of rapamycin (mTOR) signaling pathway. This research unveils how B7-H3 affects immune functions via metabolic reprogramming.

Prognostic Value of Perineural Invasion in Oral Tongue Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

OBJECTIVES: A significant number of recently published research has outlined the contribution of perineural invasion (PNI) to clinical outcomes in oral tongue squamous cell carcinoma (OTSCC), but some results remain conflicting. This study aimed to determine whether patients with OTSCC with PNI have a worse prognosis than those without PNI. MATERIALS AND METHODS: PubMed, Embase, and the Cochrane Library were queried for potentially eligible articles published up to December 2020. The primary outcomes were the hazard ratio (HR) for locoregional recurrence, overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS). The random-effect model was used in all analyses. RESULTS: Seventeen studies (4445 patients) were included. Using adjusted HRs, the presence of PNI was associated with a higher risk of locoregional recurrence (HR=1.73, 95%CI: 1.07-2.79, P=0.025, I2 = 33.1%, Pheterogeneity=0.224), worse OS (HR=1.94, 95%CI: 1.39-2.72, P<0.001, I2 = 0.0%, Pheterogeneity=0.838), worse DFS (HR=2.13, 95%CI: 1.53-2.96, P<0.001, I2 = 48.4%, Pheterogeneity=0.071), and worse CSS (HR=1.93, 95%CI: 1.40-2.65, P<0.001, I2 = 25.5%, Pheterogeneity=0.251). PNI had an impact on locoregional recurrence in early-stage OTSCC but not in all stages, and on OS, DFS, and CSS in all-stage and early-stage OTSCC. The sensitivity analyses showed that the results were robust. CONCLUSION: The presence of PNI significantly affects the locoregional recurrence and survival outcomes among patients with OTSCC.

The immunoregulatory protein B7-H3 promotes aerobic glycolysis in oral squamous carcinoma via PI3K/Akt/mTOR pathway.

OSCC (oral squamous carcinoma) is one of most common malignant cancer. Although previous studies have found abnormal expression of B7-H3 in human OSCC, the exact role and molecular mechanism of B7-H3 in OSCC remain unknown. In this study, we investigated the role of B7-H3 in glucose metabolic reprogramming of OSCC cells in vitro and in vivo. We first detected the expression of B7-H3 in OSCC samples. Next, siRNAs and overexpression short-hairpin RNA of B7-H3 were transfected into SCC25 and Cal27 cells, and cell proliferation, migration and invasion were analyzed via CCK8, colony formation and transwell assays. Then glycolysis flux was determined through measuring glucose uptake and lactate production, and mRNA and protein expression levels were determined by real-time quantitative PCR and western blot respectively. The results presented here showed B7-H3 was upregulated in OSCC samples compared with normal tissues, and the expression level was associated with tumor size and nodal metastasis. B7-H3 affects OSCC cell proliferation, migration and invasion. We also found that B7-H3 promoted the Warburg effect, evidenced by increase glucose uptake and lactate production. We further demonstrated that B7-H3 enhanced OSCC glycolysis through the upregulation of HIF-1α and its downstream targets, Glut1 and PFKFB3, which are key factors in glycolysis. Mechanically, we demonstrated that B7-H3 regulates HIF-1α expression through PI3K/Akt/mTOR pathway. Metabolic imaging of human OSCC cancer xenograft in mice confirmed that B7-H3 enhanced tumor glucose uptake, glycolysis promoted genes expression and tumor growth. Taken together, our results have unveiled a mechanism that B7-H3 drives OSCC progression through enhancing of glycolytic metabolic program in OSCC.

Digital diagnosis and treatment of mandibular condylar fractures based on Extensible Neuro imaging Archive Toolkit (XNAT).

OBJECTIVES: The treatment of condylar fractures has long been controversial. In this paper, we established a database for accurate measurement, storage, management and analysis of patients' data, in order to help determine the best treatment plan. METHODS: First of all, the diagnosis and treatment database was established based on XNAT, including 339 cases of condylar fractures and their related information. Then image segmentation, registration and three-dimensional (3D) measurement were used to measure and analyze the condyle shapes. Statistical analysis was used to analyze the anatomical structure changes of condyle and the surrounding tissues at different stages before and after treatment. The processes of condylar fracture reestablishment at different stages were also dynamically monitored. Finally, based on all these information, the digital diagnosis and treatment plans for condylar fractures were developed. RESULTS: For the patients less than 18 years old with no significant dislocation, surgical treatment and conservative treatment were equally effective for intracapsular fracture, and had no significant difference for neck and basal fractures. For patients above 18 years old, there was no significant difference between the two treatment methods for intracapsular fractures; but for condylar neck and basal fractures, surgical treatment was better than conservative treatment. When condylar fracture shift angle was greater than 11 degrees, and mandibular ramus height reduction was greater than 4mm, the patients felt the strongest pain, and their mouths opening was severely restricted. There were 170 surgical cases with condylar fracture shift angel greater than 11 degrees, and 118 of them (69.4%) had good prognosis, 52 of them (30.6%) had complications such as limited mouth opening. There were 173 surgical cases with mandibular ramus height reduction more than 4mm, and 112 of them (64.7%) had good prognosis, 61 of them (35.3%) had complications such as limited mouth opening. CONCLUSIONS: The establishment of XNAT condylar fracture database is helpful for establishing a digital diagnosis and treatment workflow for mandibular condylar fractures, providing new theoretical foundation and application basis for diagnosis and treatment of condylar fractures.

Retrospective Study on Multidrug-Resistant Bacterium Infections After Rigid Internal Fixation of Mandibular Fracture.

PURPOSE: To retrospectively investigate infection by multidrug-resistant bacteria (MDRB) after rigid internal fixation (RIF) of mandibular fracture and determine risk factors and cure methods. PATIENTS AND METHODS: From 2009 through 2014, 933 patients with mandibular fracture were enrolled in the study. Fifteen variables were statistically analyzed using univariate and multivariate logistic regression methods to investigate risk factors for MDRB infection after RIF of mandibular fracture. RESULTS: Sixteen of 933 patients (1.71%) developed MDRB infection. Of these, 6 were infected with methicillin-resistant Staphylococcus aureus (MRSA), 6 with multidrug-resistant Pseudomonas aeruginosa (MDR-PA), 1 with extended spectrum ß-lactamase-producing Klebsiella pneumonia, 1 with extended spectrum ß-lactamase-producing Escherichia coli, 1 with multidrug-resistant Acinetobacter baumannii, and 1 with multidrug-resistant Enterobacter cloacae. Univariate analysis showed that risk factors of MDRB infection after RIF of mandibular fracture were age, obesity (body mass index ≥25 kg/m(2) for Asians), polytrauma (Injury Severity Score >16), preoperative infection, open fractures, comminuted fractures accompanied by other facial fractures, and teeth involving the fracture line. Multivariate logistic regression analysis showed that obesity, preoperative infection, and open fractures were independent risk factors of MDRB infection. After systemic anti-infection treatments with vancomycin, piperacillin, tazobactam, local drainage, and debridement, the infections were under control. Fourteen patients achieved clinical healing at an average time of 8.71 months, and 2 did not achieve clinical healing. The overall mean follow-up was 18.81 months. CONCLUSION: MDRB infections occurring after RIF of mandibular fracture were caused mainly by MRSA and MDR-PA. Obesity, preoperative infection, and open fractures were the main risk factors. To lower risk, surgical debridement should be performed sooner once acute infection has been controlled, stable fixation should be achieved with the smallest amount of internal fixation material, the blood supply should be protected, and a reconstruction plate should be used to fix sites with greater stress or large comminuted fracture.

[Investigation of differences in subjective demand for orthodontic treatment of middle school students in zones with different economic levels].

OBJECTIVE: To investigate the acquaintance to orthodontics and possible factors that obstruct orthodontic treatment in middle school students in zones with different economic levels in Jiangjin, Chongqing. METHODS: The students were randomly divided into four groups: A class from a junior high school in town (group 1), a class from a senior high school in town (group 2), a class from a junior high school in the countryside (group 3), a class from a senior high school in the countryside (group 4). The information was collected by questionnaire, and the statistical analysis of results was carried out by SPSS 17.0 software. RESULTS: Sex made difference in the acquaintance to orthodontics treatment. Girls worried more about teeth extraction and pain that may occur during treatment than the boys. Students in the city had more access to related consultations compared to those in the countryside. Different economic conditions made much contribution to the proportion to go for orthodontics treatment in cities and rural areas. The evaluation from families and friends may affect patients' subjective estimation to themselves. CONCLUSION: Orthodontists should learn more about student patiens from various aspects, and make different therapies according to their sexes, economic conditions of family, education levels, etc. Only so can orthodontists get better compliance from their patients.