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Head and neck squamous cell carcinoma (HNSCC) is characterized by high frequency of early cervical lymph node metastases (LNMs), resulting in poor survival of patients. However, cervical LNMs are difficult to detect, which makes the decision-making of which patients should undergo neck dissection surgery challenging for surgeons. This study aimed to analyze the clinicopathological risk factors associated with cervical LNM and determine the indications for neck dissection in HNSCC patients.The medical records of patients diagnosed with HNSCC who were treated at our hospital between January 2010 and June 2020 were retrospectively reviewed. A database of their clinicopathological data, including sex, age at diagnosis, primary tumor regions, tumor size, and grade, was constructed. The associations of these clinicopathological features with cervical LNM were analyzed using univariate and multivariate logistic regression analyses. The TCGA database were used to externally validate the risk factors.Overall, 531 patients with HNSCC were included; 38.6% had confirmed pathological cervical LNM. Univariate and multivariate analyses identified that tumor size and grade were independent risk factors associated with LNM (odds ratio = 1.338, 95% CI: 1.015-1.767, plt; 0.05; odds ratio = 1.936, 95% CI: 1.46-2.587, plt; 0.0001, respectively). The significant positive associations of tumor size and grade with LNM were externally validated in the TCGA datasets.HNSCC patients with large tumor size or poor tumor differentiation degree were at high risk of lymph node metastasis and were recommended to undergo neck dissection.

Polyetheretherketone (PEEK) has been widely applied in orthopedics because of its excellent mechanical properties, radiolucency, and biocompatibility. However, the bioinertness and poor osteointegration of PEEK have greatly limited its further application. Growing evidence proves that physical factors of implants, including their architecture, surface morphology, stiffness, and mechanical stimulation, matter as much as the composition of their surface chemistry. This review focuses on the multiple strategies for the physical modification of PEEK implants through adjusting their architecture, surface morphology, and stiffness. Many research findings show that transforming the architecture and incorporating reinforcing fillers into PEEK can affect both its mechanical strength and cellular responses. Modified PEEK surfaces at the macro scale and micro/nano scale have positive effects on cell–substrate interactions. More investigations are necessary to reach consensus on the optimal design of PEEK implants and to explore the efficiency of various functional implant surfaces. Soft-tissue integration has been ignored, though evidence shows that physical modifications also improve the adhesion of soft tissue. In the future, ideal PEEK implants should have a desirable topological structure with better surface hydrophilicity and optimum surface chemistry.

In this study, we investigated the feasibility of using a geometrically designed anterior ramus graft to reconstruct lateral mandibular defects. This was achieved by assessing the anatomical dimensions of the mandibular ramus on computed-tomographies. The design sequence and application of the graft was also demonstrated using one of our cases. The following dimensions were measured; a and b - horizontal length from mid-ramus to the posterior and anterior ramus border respectively, c - longest length of the graft, Mp - width at the centre of the ramus, h - vertical length of the angle at its cross-section, w - horizontal length of the angle at its cross-section, x - cross-sectional area along the mandible angle. A total of 80 mandibular rami were examined. The mean length of a, b, c were 17.3 ± 1.8 mm, 15.9 ± 1.2 mm, 54.6 ± 3.8 mm, respectively. The mean width of Mp was 9.8 ± 1.1 mm. The mean cross section area of Eo-Md (x) was 326.7 ± 67.8 mm2. The average length of h and w were 26.5 ± 3.2 and 15.6 ± 2.1 mm, respectively. The use of virtual surgical planning (VSP) to geometrically design the graft was also described. Together with VSP, the anterior ramus bone graft will allow for reconstruction of the mandible with greater surgical efficiency, reduced complexity and without the need for extra-oral bone harvest. This may be an useful alternative in situations where simpler reconstructive procedures are preferred.

Background Trismus is a common problem with various causes. Any abnormal conditions of relevant anatomic structures that disturb the free movement of the jaw might provoke trismus. Trismus has a detrimental effect on the quality of life. The outcome of this abnormality is critically dependent on timely diagnosis and treatment, and it is difficult to identify the true origin in some cases. We present a rare case of trismus due to fungal myositis in the pterygoid muscle, excluding any other possible pathogenesis. Case summary The patient presented with a 2-mo history of restricted mouth opening. Computed tomography showed obvious enlargement of the left pterygoid muscles. Furthermore, the patient had trismus without obvious predisposing causes. The primary diagnosis was pterygoid myosarcoma. Consequently, lesionectomy of the left pterygoid muscle was performed. Intraoperative frozen biopsy implied the possibility of an uncommon infection. Postoperative pathologic examination confirmed myositis and necrosis in the pterygoid muscle. Fungi were detected in both muscle tissue and surrounding necrotic tissue. The patient recovered well with antifungal therapy and mouth opening exercises. The rarity of fungal myositis may be responsible for the misdiagnosis. Although the origin of pathogenic fungi is still unknown, we believe that both hematogenous spread and local invasion could be the most likely sources. To the best of our knowledge, this is the first case in the literature that reported fungal myositis in pterygoid muscles as the only reason that results in trismus. Conclusion Surgeons should remain vigilant to the possibility of trismus originating from fungal myositis.

To summary the regulatory effect of mechanical stimulation on macrophage polarization in wound healing, and explore the application prospect of mechanical stimulation in tissue engineering.The related domestic and foreign literature in recent years was extensive reviewed, and the different phenotypes of macrophages and their roles in wound healing, the effect of mechanical stimulation on macrophage polarization and its application in tissue engineering were analyzed.Macrophages have functional diversity, with two phenotypes: pro-inflammatory (M1 type) and anti-inflammatory (M2 type), and the cells exhibit different activation phenotypes and play corresponding functions under different stimuli. The mechanical force of different types, sizes, and amplitudes can directly or indirectly guide macrophages to transform into different phenotypes, and then affect tissue repair. This feature can be used in tissue engineering to selectively regulate macrophage polarization.Mechanical stimulation plays an vital role in regulating macrophage polarization, but its specific role and mechanism remain ambiguous and need to be further explored.综述创面愈合中力学刺激对巨噬细胞极化的调控作用，探讨力学刺激在组织工程中的应用前景。.广泛查阅近年来国内外相关文献，分析巨噬细胞不同表型及其在创面愈合中的作用、力学刺激在巨噬细胞表型转化中的调控作用，并探讨组织工程中利用力学刺激调控巨噬细胞极化的可能性。.巨噬细胞具有功能多样性，有促炎型（M1型）和抗炎型（M2型）两种表型，不同环境刺激下巨噬细胞呈现不同的活化表型并发挥相应功能。不同类型、大小及振幅的机械力可直接或间接引导巨噬细胞向不同表型转化，进而影响组织修复，组织工程可利用这一特点选择性调控巨噬细胞极化。.创面愈合中力学刺激对巨噬细胞极化的调控起重要作用，但具体作用及其机制尚不明确，仍待进一步研究。.

In the course of tumor progression, cancer clones interact with host normal cells, and these interactions make them under selection pressure all the time. Cell competition, which can eliminate suboptimal cells and optimize organ development via comparison of cell fitness information, is found to take place between host cells and transformed cells in mammals and play important roles in different phases of tumor progression. The aim of this study is to summarize the current knowledge about the roles and corresponding mechanisms of different cell competition interactions between host normal cells and transformed cells involved in mammalian tumor development.We reviewed the published relevant articles in the Pubmed.So far, the role of several cell competition interactions have been well described in the different phases of mammalian tumor genesis and development. While cell competitions for trophic factors and epithelial defense against cancer (EDAC) prevent the emergence of transformed cells and suppress carcinogenesis, fitness-fingerprints-comparison system and Myc supercompetitors promote the local expansion of transformed cells after the early tumor lesion is formatted. In addition, various preclinical tumor-suppression models which based on the molecular mechanisms of these competition interactions show potential clinical value of boosting the fitness of host normal cells.Cell competition between host and transformed cells has pleiotropic effects in mammalian tumor genesis and development. The clarification of specific molecular mechanisms shed light on novel ideas for the prevention and treatment of cancer.

Mesenchymal stem cells (MSCs), which are undifferentiated stem cells with the property of stemness and the potential to differentiate into multiple lineages, including osteoblasts, have attracted a great deal of attention in bone tissue engineering. Consistent with the heterogeneity of MSCs, various surface markers have been used. However, it is still unclear which markers of MSCs are best for cell amplification in vitro and later bone regeneration in vivo. Krüppel-like Factor 2 (KLF2) is an important indicator of the stemness of human MSCs (hMSCs) and as early vascularization is also critical for bone regeneration, we used KLF2 as a novel in vitro marker for MSCs and investigated the angiogenesis and osteogenesis between KLF2+ MSCs and endothelial cells (ECs). We found a synergistic interaction between hMSCs and human umbilical vein ECs (HUVECs) in that KLF2+ stemness-maintained hMSCs initially promoted the angiogenesis of HUVECs, which in turn more efficiently stimulated the osteogenesis of hMSCs. In fact, KLF2+ hMSCs secreted angiogenic factors initially, with some of the cells then differentiating into pericytes through the PDGF-BB/PDGFR-β signaling pathway, which improved blood vessel formation. The matured HUVECs in turn synergistically enhanced the osteogenesis of KLF2+ hMSCs through upregulated vascular endothelial growth factor. A three-dimensional coculture model using cell-laden gelatin methacrylate (GelMA) hydrogel further confirmed these results. This study provides insight into the stemness-directed synergistic interaction between hMSCs and HUVECs, and our results will have a profound impact on further strategies involving the application of KLF2+ hMSC/HUVEC-laden GelMA hydrogel in vascular network bioengineering and bone regeneration.

Mesenchymal stem cells (MSCs) have great therapeutic potential for tissue engineering and regenerative medicine due to their multipotency and paracrine functions. However, shortly after in vivo implantation, MSCs tend to migrate to the lungs and undergo apoptosis, which impairs their clinical efficacy. In addition, the ex vivo two-dimensional expansion of MSCs results in changes in their immunophenotype and functional activities compared to those in vivo. The use of biomaterials to culture and deliver MSCs has the potential to overcome these limitations. MSC-biomaterial constructs retain MSCs in situ and prolong their survival, while the MSCs ameliorate the foreign body reaction and fibrosis caused by the biomaterial. Biomaterial scaffolds can both preserve the tissue architecture and provide a three-dimensional biomimetic milieu for embedded MSCs, which enhance their paracrine functions, including their immunomodulatory potential. The dimensionality, physical characteristics, topographical cues, biochemistry, and microstructure can enhance the immunomodulatory potential of MSCs. Here, we review the link between the properties of biomaterial and the immunomodulatory potential of MSCs. Impact Statement Regeneration of cells, tissues, and whole organs is challenging. Mesenchymal stem cells (MSCs) have therapeutic potential in tissue engineering and regenerative medicine due to their paracrine functions, including immunomodulatory activity. The dimensionality, physical characteristics, topographical cues, biochemistry, and microstructure of biomaterial can be harnessed to enhance the immunomodulatory potential of MSCs for tissue engineering, which will increase their clinical efficacy, particularly for immune-related diseases.

A novel tri-layer membrane consisting of polycaprolactone (PCL) fibrous sheets and structured nanofibers with a gelatin (Gt) shell and a simvastatin-containing PCL core (PCL-Gt/PCL-simvastatin membrane) was prepared. The soft external layer comprised of Gt/PCL-simvastatin, the external layer of PCL and the middle layer of both microfilaments, interwoven together. The membrane was designed to promote osteoinduction and act as a barrier against cells but not against water and molecules in order to promote guided bone regeneration. The structure of the membrane was characterized by scanning electronic microscopy. The in vitro release rates of simvastatin over 32 days were determined by high-performance liquid chromatography. For in vitro biological assays, bone marrow mesenchymal stem cells and human fibroblasts were cultured on the different surfaces of the membrane. Cell adhesion, proliferation, distribution, and differentiation were examined. For in vivo testing, cranial defects were created in rabbits to assess the amount of new bone formed for each membrane. The results revealed that membranes with multi-layered structures showed good cell viability and effective osteoinductive and barrier properties. These results suggest that the novel multi-layered PCL-Gt/PCL-simvastatin membranes have great potential for bone tissue engineering.

Background: Ameloblastoma is an odontogenic tumor occurring in jaws, with local aggressiveness and postoperative recurrence. This study was aim to investigate the clinical and radiographic risk factors for recurrence in ameloblastoma. Methods: Patients diagnosed with ameloblastoma between March 2009 and March 2019 were retrospectively analyzed. Clinical and Radiological data and follow-up records were collected. Survival analyses were performed by Kaplan-Meier and log-rank tests, as well as Cox proportional hazards model. Results: One hundred and fifty-eight patients (104 males and 54 females were enrolled. The overall recurrence rate for ameloblastoma was 13.29%, and 10.76% recurred within 5 years. Most of the tumors were located in mandible (86.71%), while the rest 21 cases were in maxilla (13.29%). More than half cases (55.06%) showed multilocular radiolucency, 61 cases (38.61%) showed unilocular radiolucency. Significant differences were found with amelobastoma recurrence rate related to treatment modality, impacted tooth and root resorption (P =0.002, 0.022 and 0.007 respectively). Conclusions: Treatment modality, impacted tooth and root resorption all showed statistically significant associations with the recurrence rate in ameloblastoma. However, due to the limitation of this study, further studies are needed to reveal the true mechanism of ameloblastoma recurrence.

Gardner’s syndrome (GS) is an autosomal dominant disease characterized by the presence of familial adenomatous polyposis (FAP) as well as extraintestinal manifestations such as osteomas, dental anomalies, epidermoid cysts and ocular abnormalities. These intestinal polyps carry a 100% risk of malignant change, so early diagnosis is crucial. As craniofacial osteomas and dental anomalies of GS usually precede gastrointestinal symptoms, otolaryngologists, oral surgeons and dentists play an important role in the diagnosis of GS. GS is extensively reported in literature in the Caucasian race but not in the Mongoloid race. We report a case of a 22-year-old patient with a manifestation of three features of GS - multiple osteomas, soft tissue tumors and dental anomalies in the craniofacial region, with no intestinal polyps at the time of reporting. A family pedigree with our patient as the proband was constructed and revealed 3 consecutive generations in his lineage with GS.

Small-cell carcinomas at extrapulmonary primary sites are rare but they have been documented to arise at various locations. We report a case of small-cell carcinoma arising in the mandible, which has so far not been reported in the literature. A 37-year-old male patient underwent partial resection of the left mandible and adjuvant chemotherapy. Immunohistochemistry confirmed the diagnosis of small-cell carcinoma with neuroendocrine properties. The patient has been free of disease for 18 months after receiving treatment and was alive at the time of writing. We recommend surgical resection followed by chemotherapy for managing small-cell carcinomas in the mandibular region. Keywords: chemotherapy, immunohistochemistry, mandible, neuroendocrine system, small cell carcinoma

Mesenchymal stem cells (MSCs), which are undifferentiated stem cells with the property of stemness and the potential to differentiate into multiple lineages, including osteoblasts, have attracted a great deal of attention in bone tissue engineering. Consistent with the heterogeneity of MSCs, various surface markers have been used. However, it is still unclear which markers of MSCs are best for cell amplification in vitro and later bone regeneration in vivo. Krüppel-like Factor 2 (KLF2) is an important indicator of the stemness of human MSCs (hMSCs) and as early vascularization is also critical for bone regeneration, we used KLF2 as a novel in vitro marker for MSCs and investigated the angiogenesis and osteogenesis between KLF2

By a 7-year retrospective review, we reported our experience in management of descending necrotizing mediastinitis (DNM) and deep neck infection (DNI). A retrospective design was used to reveal the clinical characteristics of DNI and DNM. The clinical outcome was analyzed to validate less invasive management. We reviewed 82 patients between 2009 and 2016, 12 of which were diagnosed as DNM by clinical and computed tomography findings. A total of 35 patients had relevant systemic conditions, mainly diabetes mellitus (19 patients). Most cases were secondary to oropharyngeal or dental infections. All patients underwent transcervical drainage, and 10 DNM patients were treated with additional closed thoracic drainage simultaneously. Twenty patients accepted more than 1 operation. Seven patients died as a result of sepsis and/or multiple organ failure. The mortality rate in our study was similar to that in other studies. In our opinion, less invasive therapies are useful to most patients. Transcervical drainage alone is optimal management for all DNI cases and some DNM cases. Additional closed thoracic drainage is enough for type I and IIA DNM with pleural effusion or empyema.

Mesenchymal stem cells (MSCs) have shown great therapeutic potential in clinical trials; however, loss of pluripotency due to culture senescence is a major factor limiting their application. Understanding the physiology of stem cell self-renewal and stemness, and identifying the molecules that regulate these processes, are critical to future advances in tissue and organ regeneration. The Krüppel-like factor (Klf) family are key transcription factors implicated in self-renewal of embryonic stem cells. Here we identify Klf2 as a crucial transcription factor in undifferentiated human bone marrow stromal cells (hBMSCs), as indicated by gene expression in three culture media. To investigate the role of Klf2 in detail, an overexpression study using a lentiviral system in hBMSCs was performed. After Klf2 overexpression, cell proliferation was increased. The expression of pluripotency-associated genes, including Oct4, Nanog, and Rex1, was also upregulated by Klf2 overexpression. In addition, quantitative RT-PCR indicated a lower level of expression of differentiation related genes in Klf2 overexpressing cells as compared to control cells. Our results identify a functionally conserved role for Klf2 in hBMSCs, in which its expression is biologically important for stemness and self-renewal. These results are the first to show a role for Klf2 in the proliferation and pluripotency of hBMSCs.

The aim of the present study was to analyze the effect of 3 different expansion media on the expression of marker genes of mesenchymal differentiation (bone, cartilage, fat) as well as apoptosis and senescence during repeated passaging in human bone marrow stromal cells (hBMSCs) in order to identify potential expansion strategies for the use of these cells into tissue-engineered growth of bone. Medium 1 (EGF, PDGF, low Glc, 2% FCS) was associated with the highest proliferation rate compared to medium 2 (β-mercaptoethanol, high Glc DMEM, 15% FCS) and medium 3 (low Glc DMEM, 10% FCS). Real time RT-PCR indicated the lowest levels of expression of osteonectin, core binding factor-α 1, lipoprotein lipase and cartilage oligo matrix protein in medium-1 cultures as compared to media 2 and 3. Early passages expressed higher levels of peroxisome proliferator-activator receptor-γ2 in medium 1 than in media 2 and 3, whereas no difference of Sox-9 expression was noticed among the 3 media. Expression of apoptosis- and senescence-related genes (Bax, BCL-2 and P16INK4a) exhibited the lowest level of Bax/BCL-2 ratio and P16INK4a gene expression of hBMSC in medium 1. In conclusion, the replacement of FCS by recombinant EGF and PDGF promoted rapid proliferation of hBMSCs without inducing differentiation of hBMSCs. It also inhibited expression of apoptosis-related genes and limited replicative senescence during repeated passaging. Media with the lowest possible FCS content and replacement by EGF and PDGF thus should be used for 2D culturing during expansion of hBMSCs, whereas β-mercaptoethanol and high concentrations of FCS can help to commence osteogenic differentiation.