OBJECTIVE: To summarize the research progress on the role of macrophage-mediated osteoimmune in osteonecrosis of the femoral head (ONFH) and its mechanisms. METHODS: Recent studies on the role and mechanism of macrophage-mediated osteoimmune in ONFH at home and abroad were extensively reviewed. The classification and function of macrophages were summarized, the osteoimmune regulation of macrophages on chronic inflammation in ONFH was summarized, and the pathophysiological mechanism of osteonecrosis was expounded from the perspective of osteoimmune, which provided new ideas for the treatment of ONFH. RESULTS: Macrophages are important immune cells involved in inflammatory response, which can differentiate into classically activated type (M1) and alternatively activated type (M2), and play specific functions to participate in and regulate the physiological and pathological processes of the body. Studies have shown that bone immune imbalance mediated by macrophages can cause local chronic inflammation and lead to the occurrence and development of ONFH. Therefore, regulating macrophage polarization is a potential ONFH treatment strategy. In chronic inflammatory microenvironment, inhibiting macrophage polarization to M1 can promote local inflammatory dissipation and effectively delay the progression of ONFH; regulating macrophage polarization to M2 can build a local osteoimmune microenvironment conducive to bone repair, which is helpful to necrotic tissue regeneration and repair to a certain extent. CONCLUSION At present, it has been confirmed that macrophage-mediated chronic inflammatory immune microenvironment is an important mechanism for the occurrence and development of ONFH. It is necessary to study the subtypes of immune cells in ONFH, the interaction between immune cells and macrophages, and the interaction between various immune cells and macrophages, which is beneficial to the development of potential therapeutic methods for ONFH.
Humans ; Femur Head/pathology* ; Osteonecrosis/therapy* ; Macrophages/pathology* ; Inflammation ; Femur Head Necrosis/pathology*

OBJECTIVE: To obtain detailed understanding on the gene regulation of natural compounds in altering prognosis of head and neck squamous cell carcinomas (HNSC). METHODS: Gene expression data of HNSC samples and peripheral blood mononuclear cells (PBMCs) of HNSC patients were collected from Gene Expression Omnibus (GEO). Differential gene expression analysis of GEO datasets were achieved by the GEO2R tool. Common differentially expressed gerres (DEGs) were screened by comparing DEGs of HNSC with those of PBMCs. The combination was further analyzed for regulating pathways and biological processes that were affected. RESULTS: Totally 110 DEGs were retrieved and identified to be involved in biological processes related to tumor regulation. Then 102 natural compounds were screened for a combination such that the expression of all 110 commonly DEGs was altered. A combination of salidroside, ginsenoside Rd, oridonin, britanin, and scutellarein was chosen. A multifaceted, multi-dimensional tumor regression was showed by altering autophagy, apoptosis, inhibiting cell proliferation, angiogenesis, metastasis and inflammatory cytokines production. CONCLUSIONS This study has helped develop a unique combination of natural compounds that will markedly reduce the propensity of development of drug resistance in tumors and immune evasion by tumors. The result is crucial to developing a combinatorial natural therapeutic cocktail with accentuated immunotherapeutic potential.
Humans ; Leukocytes, Mononuclear ; Head and Neck Neoplasms/drug therapy* ; Squamous Cell Carcinoma of Head and Neck/drug therapy* ; Immunotherapy ; Prognosis

Humans ; Artificial Intelligence ; Algorithms ; Brain ; Head

Existing studies have underscored the pivotal role of N-acetyltransferase 10 (NAT10) in various cancers. However, the outcomes of protein-protein interactions between NAT10 and its protein partners in head and neck squamous cell carcinoma (HNSCC) remain unexplored. In this study, we identified a significant upregulation of RNA-binding protein with serine-rich domain 1 (RNPS1) in HNSCC, where RNPS1 inhibits the ubiquitination degradation of NAT10 by E3 ubiquitin ligase, zinc finger SWIM domain-containing protein 6 (ZSWIM6), through direct protein interaction, thereby promoting high NAT10 expression in HNSCC. This upregulated NAT10 stability mediates the enhancement of specific tRNA ac⁴C modifications, subsequently boosting the translation process of genes involved in pathways such as IL-6 signaling, IL-8 signaling, and PTEN signaling that play roles in regulating HNSCC malignant progression, ultimately influencing the survival and prognosis of HNSCC patients. Additionally, we pioneered the development of TRMC-seq, leading to the discovery of novel tRNA-ac⁴C modification sites, thereby providing a potent sequencing tool for tRNA-ac⁴C research. Our findings expand the repertoire of tRNA ac⁴C modifications and identify a role of tRNA ac⁴C in the regulation of mRNA translation in HNSCC.
Humans ; DNA-Binding Proteins ; Head and Neck Neoplasms/genetics* ; N-Terminal Acetyltransferases ; RNA, Transfer ; Serine ; Signal Transduction ; Squamous Cell Carcinoma of Head and Neck

Wnt signaling are critical pathway involved in organ development, tumorigenesis, and cancer progression. WNT7A, a member of the Wnt family, remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma (HNSCC). According to the Cancer Genome Atlas (TCGA), transcriptome sequencing data of HNSCC, the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues, which was validated using Real-time RT-PCR and immunohistochemistry. Unexpectedly, overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC. Instead, our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway, leading to enhanced cell proliferation, self-renewal, and resistance to apoptosis. Furthermore, in a patient-derived xenograft (PDX) tumor model, high expression of WNT7A and phosphorylated STAT3 was observed, which positively correlated with tumor progression. These findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.
Animals ; Humans ; Squamous Cell Carcinoma of Head and Neck ; Carcinogenesis/genetics* ; Cell Transformation, Neoplastic ; Wnt Signaling Pathway ; Disease Models, Animal ; Head and Neck Neoplasms/genetics* ; Wnt Proteins ; Frizzled Receptors/genetics* ; Janus Kinase 1 ; STAT3 Transcription Factor

Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment. Oral squamous cell carcinoma (OSCC), a representative hypoxic tumor, has a heterogeneous internal metabolic environment. To clarify the relationship between different metabolic regions and the tumor immune microenvironment (TME) in OSCC, Single cell (SC) and spatial transcriptomics (ST) sequencing of OSCC tissues were performed. The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data. The metabolic activity of each spot was calculated using scMetabolism, and k-means clustering was used to classify all spots into hyper-, normal-, or hypometabolic regions. CD4T cell infiltration and TGF-β expression is higher in the hypermetabolic regions than in the others. Through CellPhoneDB and NicheNet cell-cell communication analysis, it was found that in the hypermetabolic region, fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts (iCAFs), and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12. The secretion of CXCL12 recruits regulatory T cells (Tregs), leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment. This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC, ST and TCGA bulk data, and highlights potential targets for therapy.
Humans ; Carcinoma, Squamous Cell/metabolism* ; Squamous Cell Carcinoma of Head and Neck ; Mouth Neoplasms/metabolism* ; Immunosuppression Therapy ; Transforming Growth Factor beta ; Head and Neck Neoplasms ; Gene Expression Profiling ; Tumor Microenvironment

Objective: To investigate the association between the time intervals of key clinical time points and tumor progression (increase in clinical staging) in head and neck cancer patients before and during the pandemic. Methods: Design: Retrospective Cohort Study. Setting: Tertiary Government Training Hospital. Participants: A total of 81 head and neck cancer patients who consulted at the OPD and underwent elective surgery between January 1, 2018, and December 31, 2022, under the Department of Otorhinolaryngology – Head and Neck Surgery of East Avenue Medical Center were included in the study; 40 patients comprised the pre-pandemic group and 41 patients-the pandemic group. Results: Majority of patients were men (61.73%), and the mean age was 54 years. The most prevalent tumor site was the oral cavity (37.04%). Most patients were Clinical Stage IV at the time of diagnosis (32.10%) and at the time of surgery (58.02%). In the pre-pandemic period, median time-to-consult was 180 days, time-to-diagnosis was 14 days, and time-to-treatment was 57 days. During the pandemic, median time-to-consult significantly increased to 365 days (Mann-Whitney test, U = 589, p = .028), but time-to-diagnosis decreased to 10 days, and time to-treatment decreased to 43 days, although these were not significant (U = 775, p = .667; U = 809, p = .917). Among the 81 patients in the study, 14 (17.28%) showed tumor progression (pre-pandemic: 6; 15%; pandemic: 8; 19.51%), but there was no significant association between time-to-consult and increase in clinical staging for both pre-pandemic (χ2(38) = 34.2, p = .646) and pandemic groups (χ2(16) = 23.1, p = .110) or between time-to-diagnosis and increase in clinical staging for pre-pandemic (χ2(56) = 36.8, p = .978) and pandemic groups (χ2(23) = 28.3, p = .267). Overall, there was no significant association between time-to-treatment and increase in clinical staging for both pre-pandemic (χ2(62) = 80.00, p = .062) and pandemic groups (χ2(32) = 30.4, p = .548), but a subset of patients with larynx primary tumor site had a statistically significant association between time-to-treatment and tumor progression (χ2(5) = 12.00, p = .035). Conclusion This study revealed that there was an increase in time to-consult for head and neck cancer patients during the pandemic. However, there was no significant difference in time-to-diagnosis and time-to-treatment. This shows that the Department of ORL-HNS, East Avenue Medical Center has provided pandemic head and neck cancer care similar to before the pandemic. No significant associations were found between tumor progression and time intervals of the key clinical time points but patients who had an increase in clinical stage were noted with longer time-to treatment. It was also observed that more patients were in advanced clinical stages during the pandemic.
Head and Neck Neoplasms ; Time-to-Treatment ; COVID-19

Objective: To identify in what phases in the treatment of head and neck cancer do delays happen at a tertiary hospital and to determine the association between the length of treatment delays and the oncologic outcomes (disease-free survival and overall survival) for patients with head and neck cancer. : Methods Design: Retrospective Cohort Study Setting: Tertiary National University Hospital Participants: Sixty-eight (68) patients who had surgery and adjuvant radiotherapy for invasive head and neck cancer at the Philippine General Hospital during the 5-year period of January 2014 to December 2019 were included in the initial consideration. Only 15 had survival data and were thus eligible for inclusion in this study. Results: The median treatment package time for head and neck cancers in our institution was 27.6 weeks or 193 days. The treatment package time statistically correlated with both overall survival, F(1,13)=12.952, p <0.005, R2=0.499, and disease-free survival, F(1-13)=12.823, p <0.005, R2= 0.497. However, the independent effects of other predictors such as time interval between first consult to histopathologic diagnosis, diagnosis to surgery, and surgery to post-operative radiotherapy, showed no statistically significant association with overall survival and disease free survival. Conclusion All study patients experienced treatment delays from diagnosis to surgery, and surgery to adjuvant radiation therapy, and in their total treatment package time. The positive correlation among treatment package time, and disease-free and overall survival in this study must be further investigated in order to elucidate the true effect of delays across time intervals in the treatment of head and neck cancer in the Philippine General Hospital. Every effort should be made towards timely management of these patients.
Head and Neck Neoplasms ; Radiotherapy ; Survival Rate ; Treatment Outcome ; Time-to-Treatment ; Surgery ; Disease-Free Survival ; Delayed Diagnosis ; Retrospective Studies ; Postoperative Care

Objective: To determine the sensitivity, specificity, positive predictive value, negative predictive value and safety of endoscopic guided office-based biopsies (OBB) in diagnosing laryngeal and pharyngeal neoplasms at the St. Luke’s Medical Center in Quezon City and Global City. : Methods Design: Diagnostic Accuracy Study Setting: Two Tertiary Private Training Hospitals Participants: Records of patients with pharyngeal and laryngeal lesions who underwent endoscopic-guided OBB were included in the study describing safety. Only patients with subsequent operative biopsies were included in assessing diagnostic accuracy. Results: Thirty-six (36) patients were included: 28 (77.78%) males and 8 (22.22%) females, with median age of 61.5 (IQR 52-73 years). Nearly half (16/36; 44.44%) of the office-based biopsies yielded malignant histopathology results, 19.44% had high grade dysplasia while 36.11% had benign findings. Of 10 patients with operative biopsy for definitive diagnosis, 8 were correctly diagnosed with carcinoma while one had a change in diagnosis from benign to malignant. Office based biopsy was well tolerated and had no complications reported. Overall, the sensitivity of OBB in predicting malignancy was 88.89%, specificity was 100%, positive predictive value was 100%, and negative predictive value was 50%. Conclusion Office-based biopsy is an accurate, reliable and safe modality for screening suspicious pharyngeal and laryngeal neoplasms, and may be part of routine screening during initial endoscopy among selected patients with suspicious pharyngeal and laryngeal neoplasms. Further investigation and larger population studies may provide more robust insights on effectiveness and safety of office-based biopsy in diagnosis of pharyngeal and laryngeal neoplasms.
Head and Neck Neoplasms ; Malignancy ; Neoplasms

: This is a case of a 6-year-old male who had a motor vehicular accident, who initially presented without neurologic deficit immediately post injury but followed up with seizures and motor weakness. The aim of the study is to review the pathomechanism of traumatic aneurysm in blunt head trauma in pediatric patients. : The initial imaging done revealed a closed, depressed comminuted fracture in the left frontal bone. Three weeks post-injury, he had recurrent generalized tonic clonic seizures and angiogram showed saccular aneurysm of the left A2 with left frontal intracerebral hemorrhage (ICH). The patient underwent bifrontal craniotomy, clipping of aneurysm and evacuation of the ICH. Treatment options includes endovascular approach, wrapping and trapping the aneurysm. However, there is no single modality indicated for all lesions. Post operatively, the patient was aphasic with right hemiparesis (2/5). Speech improved the second week after the surgery. Rehabilitation was initiated after admission and unassisted ambulation noted after 2 months. Work up done for other possible causes of aneurysm in the pediatric population revealed unremarkable findings. Mechanism associated with blunt traumatic head injury in the development of aneurysm could be secondary to a shear or rotational injury damaging vessels in close proximity to dura, for instance in this case, close to the falx cerebri.
blunt head injury