Fever is an increase in body temperature beyond the normal range, acting as a protective inflammatory mechanism. This article summarizes diseases with fever encountered in dental clinics, including what is known about pyrexia in coronavirus infection, and further proposes a "six steps in one" identification and analysis strategy to guide the clinical work of stomatology.
Humans ; Dental Clinics ; Fever/diagnosis* ; Coronavirus Infections

Proliferative verrucous leukoplakia (PVL) is one of the oral potentially malignant disorders (OPMD) with the highest malignant potential. PVL tends to be easily misdiagnosed owing to the resemblance in clinical manifestations between PVL and other diseases such as oral leukoplakia or oral lichen planus. PVL is considered as a special type of oral leukoplakia by some scholars, which is characterized by its tendency of recurrence and metastasis, along with its high risk of malignant transformation. So far, the accurate clinic diagnosis and management of PVL are still intractable due to the lack of definite histopathological definition, unified diagnostic criteria and effective treatment modalities. This review aims to provide the clinical practitioners with a series of advices on the clinical diagnosis and management of PVL by systematically reviewing the diagnostic logistics, therapeutic strategies, malignant transformation detection based on tremendous relevant data and evidence-based medicine.

The heterogeneity of exhausted T cells (Tex) is a critical determinant of immune checkpoint blockade therapy efficacy. However, few studies have explored exhausted T cell subpopulations in human cancers. In the present study, we examined samples from two cohorts of 175 patients with head and neck squamous cell cancer (HNSCC) by multiplex immunohistochemistry (mIHC) to investigate two subsets of Tex, CD8⁺PD1⁺TCF1⁺ progenitor exhausted T cells (TCF1⁺Tex^prog) and CD8⁺PD1⁺TCF1^- terminally exhausted T cells (TCF1^-Tex^term). Moreover, fresh tumor samples from 34 patients with HNSCC were examined by flow cytometry and immunohistochemistry to further investigate their properties and cytotoxic capabilities and their correlation with regulatory T cells (Tregs) in the tumor immune microenvironment (TIME). mIHC and flow cytometry analysis showed that TCF1^-Tex^term represented a greater proportion of CD8⁺PD1⁺Tex than TCF1⁺Tex^prog in most patients. TCF1⁺Tex^prog produced abundant TNFα, while TCF1^-Tex^term expressed higher levels of CD103, TIM-3, CTLA-4, and TIGIT. TCF1^-Tex^term exhibited a polyfunctional TNFα⁺GZMB⁺IFNγ⁺ phenotype; and were associated with better overall survival and recurrence-free survival. The results also indicated that larger proportions of TCF1^-Tex^term were accompanied by an increase in the proportion of Tregs. Therefore, it was concluded that TCF1^-Tex^term was the major CD8⁺PD1⁺Tex subset in the HNSCC TIME and that these cells favor patient survival. A high proportion of TCF1^-Tex^term was associated with greater Treg abundance.
CD8-Positive T-Lymphocytes ; Head and Neck Neoplasms/therapy* ; Humans ; Immunotherapy/methods* ; Prognosis ; Programmed Cell Death 1 Receptor ; Squamous Cell Carcinoma of Head and Neck/therapy* ; Tumor Microenvironment ; Tumor Necrosis Factor-alpha

Considering the substantial role played by dendritic cells (DCs) in the immune system to bridge innate and adaptive immunity, studies on DC-mediated immunity toward biomaterials principally center on their adjuvant effects in facilitating the adaptive immunity of codelivered antigens. However, the effect of the intrinsic properties of biomaterials on dendritic cells has not been clarified. Recently, researchers have begun to investigate and found that biomaterials that are nonadjuvant could also regulate the immune function of DCs and thus affect subsequent tissue regeneration. In the case of proteins adsorbed onto biomaterial surfaces, their intrinsic properties can direct their orientation and conformation, forming "biomaterial-associated molecular patterns (BAMPs)". Thus, in this review, we focused on the intrinsic physiochemical properties of biomaterials in the absence of antigens that affect DC immune function and summarized the underlying signaling pathways. Moreover, we preliminarily clarified the specific composition of BAMPs and the interplay between some key molecules and DCs, such as heat shock proteins (HSPs) and high mobility group box 1 (HMGB1). This review provides a new direction for future biomaterial design, through which modulation of host immune responses is applicable to tissue engineering and immunotherapy.
Biocompatible Materials/metabolism* ; Dendritic Cells/metabolism* ; Tissue Engineering ; Immunomodulation ; Adaptive Immunity

Infectious diseases are caused by infection of organism with pathogenic agents, which may lead to epidemics. Many infectious diseases such as syphilis, diphtheria, measles, and acquired immunodeficiency syndrome have specific and non-specific manifestations in the oral cavity. However, the same disease may have different oral manifestations in different patients clinically. We can apply the strategy of "three unusuals and one change" in clinical reasoning for diagnosis of infectious diseases with oral manifestations. The so-called "three unusuals" refer to unusual age, unusual location and unusual effect, and "one change" means the change from rare to common. In this article, we will give a comprehensive introduction about the oral manifestations of common communicable diseases and their diagnostic strategies.
Acquired Immunodeficiency Syndrome ; Humans ; Measles ; Syphilis

Objective:To investigate MAML2 gene rearrangement, gene fusion patterns, and the clinicopathological characteristics of primary pulmonary mucoepidermoid carcinoma (PMEC).Methods:Forty-six cases of primary PMEC from Fudan University Zhongshan Hospital and Fudan University Shanghai Cancer Center between 2017 and 2020 were collected. MAML2 gene rearrangement in all cases was detected by fluorescence in situ hybridization (FISH). In 20 cases, MAML2 fusion patterns were detected by targeted RNA sequencing (RNAseq). The relationship between MAML2 gene rearrangement, fusion patterns, clinicopathological characteristics, and prognosis was analyzed.Results:The average age of PMEC patients was 41 years (range 15-71 years); the ratio of male to female was about 1.1 ∶ 1.0. Most PMECs were low grade in histopathology with an early clinical stage (stageⅠ-Ⅱ).The overall positive rate of MAML2 gene rearrangement detected by FISH was about 80.4% (37/46), and the rate was higher in low-grade PMEC (91.7%, 33/36). Of the 20 cases detected by RNAseq, all the 19 FISH positive cases showed gene fusion, mainly CRTC1-MAML2 fusion (16/19), the other three cases showed CRTC3-MAML2 fusion (3/19), the break point of all the fusion patterns was CRTC1/3 (exon 1)-MAML2 (exon 2); No gene fusion was detected in the single FISH negative case; Compared with the MAML2 FISH negative patients, the PMECs carrying CRTC1-MAML2 fusion were more commonly found in patients age ≤ 40 years, maximum tumor diameter ≤ 2 cm, low histopathological grade and early clinical stage (all P<0.05); The three PMECs carrying CRTC3-MAML2 fusion gene were all female with early clinical stage; Univariate analysis showed that MAML2 gene rearrangement/fusion, onset age ≤ 40 years old, smaller tumor size, low histopathological grade, early clinical stage, no metastasis at diagnosis and surgical treatment were significantly correlated with overall survival ( P<0.05), but Cox regression analysis suggested that none of the above indicators were the independent prognostic factors for the survival of PMEC. Conclusions:The high incidence of MAML2 gene rearrangement in PMEC suggests that it is an important molecular diagnostic marker of PMEC. RNAseq confirms that CRTC1/3-MAML2 is the main fusion pattern in PMEC, suggesting that MAML2 fusion transcription may be an important driving factor of PMEC. MAML2 rearrangement/fusion and related clinicopathological characteristics are associated with good prognosis.

It has been reported that ACE2 is the main host cell receptor of 2019-nCoV and plays a crucial role in the entry of virus into the cell to cause the final infection. To investigate the potential route of 2019-nCov infection on the mucosa of oral cavity, bulk RNA-seq profiles from two public databases including The Cancer Genome Atlas (TCGA) and Functional Annotation of The Mammalian Genome Cap Analysis of Gene Expression (FANTOM5 CAGE) dataset were collected. RNA-seq profiling data of 13 organ types with para-carcinoma normal tissues from TCGA and 14 organ types with normal tissues from FANTOM5 CAGE were analyzed in order to explore and validate the expression of ACE2 on the mucosa of oral cavity. Further, single-cell transcriptomes from an independent data generated in-house were used to identify and confirm the ACE2-expressing cell composition and proportion in oral cavity. The results demonstrated that the ACE2 expressed on the mucosa of oral cavity. Interestingly, this receptor was highly enriched in epithelial cells of tongue. Preliminarily, those findings have explained the basic mechanism that the oral cavity is a potentially high risk for 2019-nCoV infectious susceptibility and provided a piece of evidence for the future prevention strategy in dental clinical practice as well as daily life.

With recent developments in photosensitizers and light delivery systems, topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) has become the fourth alternative therapeutic approach in the management of oral leucoplakia (OLK) due to its minimally invasive nature, efficacy, and low risk of systemic side effects and disfigurement. This report presents step-by-step guidelines for applying topical ALA-PDT in the management of OLK based on both the clinical experience of the authors and a systematic review of the current literature. Studies using protocols with standardized parameters and randomized clinical trials at multiple centres with adequate sample sizes and both interim and long-term follow-ups are needed before universally applicable guidelines can be produced in this field.
Aminolevulinic Acid ; administration & dosage ; therapeutic use ; Humans ; Leukoplakia, Oral ; therapy ; Photochemotherapy ; methods ; Photosensitizing Agents ; administration & dosage ; therapeutic use ; Practice Guidelines as Topic

Proteases are important molecules that are involved in many physiological and pathological processes of the human body, such as growth, apoptosis and metastasis cancer cells. They are potential targets in cancer diagnosis and biotherapy. In this study, we analyzed the salivary protease spectrum of patients with oral squamous cell carcinoma (OSCC), oral benign masses and chronic periodontitis, as well as that of health, using human protease array kits, enzyme-linked immunosorbent assay, western blot and immunofluorescence. The salivary protease spectrum was found to be associated with oral diseases. For example, the saliva of patients with OSCC contained increased numbers of proteases than those of other oral diseases and health. The levels of matrix metalloproteinase (MMP)-1, MMP-2, MMP-10, MMP-12, A disintegrin and metalloprotease (ADAM)9, A disintegrin and metalloprotease with thrombospondin type 13 motifs (ADAMST13), cathepsin V and kallikrein 5 in the saliva of patients with OSCC were significantly increased compared with those of other groups. Taking MMP-1, cathepsin V, kallikrein 5 and ADAM9 as biomarkers of OSCC, cutoff values were199, 11.34, 9.29 and 202.55 pg·mL, respectively. From the area under the curve, sensitivity and specificity, the combination of cathepsin V/kallikrein5/ADAM9 was an optimal biomarker for diagnosing OSCC. Thus, analysis of the salivary protease spectrum may be an innovative and cost-efficient approach to evaluating the health status of the oral cavity. Specifically, increases in cathepsin V, kallikrein 5 and ADAM9 may be useful biomarkers in the screening and diagnosis of OSCC.
ADAM Proteins ; Biomarkers, Tumor ; analysis ; Carcinoma, Squamous Cell ; diagnosis ; metabolism ; Humans ; Matrix Metalloproteinase 9 ; analysis ; Membrane Proteins ; Mouth Neoplasms ; diagnosis ; metabolism ; Saliva ; chemistry

Objective To study the effect of atrial natriuretic peptide(ANP)deletion on melanoma growth. Methods A subcutaneous xenotransplanted melanoma model was established in ANP knockout mice and C57BL/6J mice. The tumor volume was measured at the sixth day after establishment of the subcutaneous transplantation. Tumor cell proliferation and tumor-induced angiogenesis were detected by immunohistochemical staining. Results The volume and weight of xenotransplanted melanoma were significantly decreased in the ANP knockout mice compared with those in the C57BL/6J mice. The proliferative tumor cells and microvessel density were significantly decreased in the tumor tissues of ANP knockout mice compared with those in the C57BL/6J mice. Conclusions ANP deletion significantly suppresses xenotransplanted melanoma growth through inhibiting the tumor cell proliferation and angiogenesis.