The role of HPV11 E7 in modulating STING-dependent interferon ß response in recurrent respiratory papillomatosis.

Recurrent respiratory papillomatosis (RRP) is a rare benign tumor caused mainly by the infection of the respiratory tract epithelial cells by the human papillomavirus (HPV) type 6/11. However, the specific mechanisms underlying the inhibition of the host's innate immune response by HPV remain unclear. For this purpose, we employed single-cell RNA sequencing to analyze the states of various immune cells in RRP samples post-HPV infection and utilized a cellular model of HPV infection to elucidate the mechanisms by which HPV evades the innate immune system in RRP. The results revealed distinct immune cell heterogeneity in RRP and demonstrated that HPV11 E7 can inhibit the phosphorylation of the stimulator of interferon genes protein, thereby circumventing the body's antiviral response. In vitro co-culture experiments demonstrated that stimulation of macrophages to produce interferon-beta induced the death of HPV-infected epithelial cells, also reducing HPV viral levels. In summary, our study preliminarily identifies the potential mechanisms by which HPV evades the host's antiviral immune response, as well as the latent antiviral functions exhibited by activated macrophages. This research serves as an initial exploration of antiviral immune evasion in RRP, laying a solid foundation for investigating immunotherapeutic approaches for the disease.IMPORTANCESurgical tumor reduction is the most common treatment for recurrent respiratory papillomatosis (RRP). One of the characteristics of RRP is its persistent recurrence, and multiple surgeries are usually required to control the symptoms. Recently, some adjuvant therapies have shown effectiveness, but none of them can completely clear human papillomavirus (HPV) infection, and thus, a localized antiviral immune response is significant for disease control; after all, HPV infection is limited to the epithelium. Inhibition of interferon-beta (IFN-ß) secretion by HPV11 E7 viral proteins in epithelial cells by affecting stimulator of interferon genes phosphorylation may account for the persistence of low-risk HPV replication in the RRP. Moreover, suppression of the IFN-I pathway in RRP cell types might provide clues regarding the hyporeactive function of local immune cells. However, activation of macrophage groups to produce IFN-ß can still destroy HPV-infected cells.

Effectiveness of surgery combined with photodynamic therapy for recurrent respiratory papillomatosis.

OBJECTIVE: This study aims to analyze the safety and effectiveness of a new model of surgery combined with Photodynamic therapy for treating Recurrent Respiratory Papillomatosis (RRP). METHODS: Review the case data of patients with RRP who opted for comprehensive surgery combined with Photodynamic therapy at the Nanjing BenQ Medical Center, from January 2021 to May 2023. The efficacy of this program was evaluated by comparing the annual number of surgeries and Derkay scores before and after the surgery. RESULTS: A total of 23 RRP patients were included in the study. After treatment, the recurrence rate was 65.2 % (15/23), with an average recurrence time of 94.3 ± 50.8 days. The average Derkay score at the time of recurrence was significantly lower than the average pre-treatment Derkay score (P < 0.001). The average annual recurrence rate before treatment was 2.2 ± 1.3, compared to 1.5 ± 1.5 after treatment, with no significant difference (P = 0.16). However, subgroup analysis revealed a significant decrease in the annual recurrence rate of adult-onset RRP after treatment (P = 0.01). The most common adverse reaction was mild pharyngeal pain (11/23). There were 3 cases of new-onset vocal cord adhesions. No patients experienced serious respiratory-related adverse reactions, anesthesia-related adverse reactions, or systemic phototoxic reactions. CONCLUSION: In conclusion, this study indicates that surgery combined with Photodynamic therapy (PDT) might be a safe and effective option for treating RRP, especially in patients with Adult-Onset Recurrent Respiratory Papillomatosis (AORRP).

Recurrence and malignant transformation of laryngeal leukoplakia treated with CO2 laser: A systematic review and meta-analysis.

BACKGROUND: Laryngeal leukoplakia (LL) is a white lesion with high potential of recurrence and malignant transformation. Currently, CO2 laser has become the primary surgical treatment for LL, and the recurrence and malignant transformation rates after treatment vary widely. OBJECTIVE: We performed a systematic review and meta-analysis dedicated to evaluating the rates of recurrence and malignant transformation of LL lesions treated with CO2 laser and exploring relevant risk factors for recurrence or malignant transformation. METHODS: Literature searches were conducted on ProQuest, PubMed, Web of Science, Ovid Medline, Embase, and Cochrane databases. Some articles identified through hand searching were included. RESULTS: A total of 14 articles and 1462 patients were included in this review. Pooled results showed that the overall recurrence rate was 15%, and the malignant transformation rate was 3%. Subgroup analysis showed that the dysplasia grade was not a significant risk factor for the recurrence and malignant transformation of LL (P > .05). CONCLUSIONS: The results of this systematic review and meta-analysis suggest that the CO2 laser is a safe and effective surgical instrument for the excision of LL, which yields low rates of recurrence and malignant transformation. The risk factors relevant to recurrence or malignant transformation remain unclear and require further investigation.

RUNX1 promotes MAPK signaling to increase tumor progression and metastasis via OPN in head and neck cancer.

Tumor progression and metastasis are still major burdens for head and neck squamous cell carcinoma (HNSCC). Runt-related transcription factor 1 (RUNX1) is involved in aggressive phenotypes in several cancers, while the molecular role of RUNX1 underlying cancer progression and metastasis of HNSCC remains largely unknown. In our study, RUNX1 expression was increased with disease progression in patients with HNSCC. The silencing of RUNX1 significantly decelerated the malignant progression of HNSCC cells, reduced osteopontin (OPN) expression in vitro and weakened the tumorigenicity of HNSCC cells in vivo. Moreover, we demonstrated that RUNX1 activated the mitogen-activated protein kinase signaling by directly binding to the promoter of OPN in tumor progression and metastasis of HNSCC. Our results may provide new insight into the mechanisms underlying the role of RUNX1 in tumor progression and metastasis and reveal the potential therapeutic target in HNSCC.

Upregulation of secreted phosphoprotein 1 affects malignant progression, prognosis, and resistance to cetuximab via the KRAS/MEK pathway in head and neck cancer.

Acquired resistance is a barrier to cetuximab efficacy in patients with head and neck squamous cell carcinoma (HNSCC). Secreted phosphoprotein 1 (SPP1) is involved in various biological processes, including immune responses, cancer progression, and prognosis in many cancers, while little is known in HNSCC. Bioinformatics methods were used to identify candidate genes and further in vivo and in vitro experiments were performed to examine and validate the function of SPP1. We found that SPP1 was upregulated and has been found to have an oncogenic role in HNSCC. We further confirmed that overexpression of SPP1 affected proliferation, migration, invasion, and survival, and inhibited apoptosis, whereas silencing of SPP1 yielded opposite results to those of SPP1 overexpression. In addition, activation of the KRAS/MEK pathway contributed to the SPP1-induced malignant progression of HNSCC and resistance to cetuximab. Furthermore, SPP1 knockdown or an MEK inhibitor overcame this cetuximab-resistance pattern. Taken together, our findings for the first time identify the role of SPP1 in tumor promotion, prognostic prediction, and potential therapeutic targeting, as well as resistance to cetuximab in HNSCC.

GFRα1 released by nerves enhances cancer cell perineural invasion through GDNF-RET signaling.

The ability of cancer cells to invade along nerves is associated with aggressive disease and diminished patient survival rates. Perineural invasion (PNI) may be mediated by nerve secretion of glial cell line-derived neurotrophic factor (GDNF) attracting cancer cell migration through activation of cell surface Ret proto-oncogene (RET) receptors. GDNF family receptor (GFR)α1 acts as coreceptor with RET, with both required for response to GDNF. We demonstrate that GFRα1 released by nerves enhances PNI, even in the absence of cancer cell GFRα1 expression. Cancer cell migration toward GDNF, RET phosphorylation, and MAPK pathway activity are increased with exposure to soluble GFRα1 in a dose-dependent fashion. Dorsal root ganglia (DRG) release soluble GFRα1, which potentiates RET activation and cancer cell migration. In vitro DRG coculture assays of PNI show diminished PNI with DRG from GFRα1(+/-) mice compared with GFRα1(+/+) mice. An in vivo murine model of PNI demonstrates that cancer cells lacking GFRα1 maintain an ability to invade nerves and impair nerve function, whereas those lacking RET lose this ability. A tissue microarray of human pancreatic ductal adenocarcinomas demonstrates wide variance of cancer cell GFRα1 expression, suggesting an alternate source of GFRα1 in PNI. These findings collectively demonstrate that GFRα1 released by nerves enhances PNI through GDNF-RET signaling and that GFRα1 expression by cancer cells enhances but is not required for PNI. These results advance a mechanistic understanding of PNI and implicate the nerve itself as a key facilitator of this adverse cancer cell behavior.

Clinicopathologic and prognostic factors in adenoid cystic carcinoma of head and neck minor salivary glands: A clinical analysis of 130 cases.

PURPOSE: This study was to investigate clinicopathologic characteristics and prognostic factors in adenoid cystic carcinoma of head and neck minor salivary glands. MATERIALS AND METHODS: We conducted a retrospective review of 130 patients with adenoid cystic carcinoma of head and neck minor salivary glands that were evaluated between 2000 and 2013 in Beijng Tongren Hospital. RESULTS: Five-year overall survival and disease-free survival rates were 80.8% and 55.6%. Local recurrence rate was 40%, regional recurrence 3.8%, and distant metastasis was 28.5%. On univariate analysis, solid histological subtype, perineural invasion, positive surgical margins and advanced stages were found to be poor prognostic indicators. On multivariate analysis, solid histological subtype and positive surgical margins were significant prognostic factors of worse overall survival. CONCLUSIONS: Solid histological subtype and positive surgical margins were the most important predictors of poor outcome in adenoid cystic carcinoma of minor salivary glands. Surgery with postoperative radiation were recommended treatment and offered durable local control.

Enumeration and molecular characterization of circulating tumor cell using an in vivo capture system in squamous cell carcinoma of head and neck.

OBJECTIVE: Detection rate and isolation yield of circulating tumor cell (CTC) are low in squamous cell carcinoma of head and neck (SCCHN) with in vitro approaches due to limited sample volumes. In this study, we applied the CellCollector to capture CTC in vivo from peripheral blood. METHODS: In total, the study included 22 cases with 37 times of detection. All of the patients were newly diagnosed with locally advanced or metastatic SCCHN, including laryngocarcinoma (40.9%, 9/22) and hypopharyngeal carcinoma (59.1%, 13/22). All patients received CTC analysis before treatment. Three patients received induction chemotherapy. Sixteen patients received surgical therapy, of which 13 patients received postoperative detection. Two patients received both induction chemotherapy and surgery treatment. Patients underwent two successive CellCollector applications 24 h before and 7 d after surgical therapy. Nine healthy volunteers were enrolled as the control group. Epidermal growth factor receptor variant type III (EGFRVIII) expression was analyzed with fluorescent dye labeled antibody. RESULTS: With CellCollector isolation, 72.7% (16/22) of the patients were positive for ≥1 CTC (CTC; range, 1-17 cells) before treatments and 46.7% (7/15) of patients were CTC positive for ≥1 CTC (CTC; range, 1-29 cells) after surgical therapy. Moreover, the detection rate of CellCollector (82.4%, 14/17; CTC count range, 0-17) in advanced SCCHN (stage III-IV) was much higher than that in early stages (stage I-II, 40.0%, 2/5; CTC count range, 0-2) (P<0.05). EGFRVIII expression of CTC was also analyzed with fluorescence staining. One CTCEGFRVIII-positive patient was detected from six CTC-positive patients, and the positive expression of EGFRVIII was also found in the tumor tissue of this patient. CONCLUSIONS: In vivo detection of CTCs had high sensitivity in SCCHN, which might improve CTC application in clinic.

Nanosecond laser pulse induced concentric surface structures on SiO2 layer.

We report the periodic concentric surface structures on SiO2 layer induced by a single shot nanosecond laser pulse at 1.06 µm. The fringe period of the structures ranges from 7.0 µm to 26.8 µm, depending on the laser fluence and the distance from central defect precursor. The size and depth of the damage sites increase almost linearly with the laser fluence from 19.6 J/cm(2) to 61 J/cm(2). Plasma flash was clearly observed during the damage process. We attribute the formation mechanism of the structures to the interference between the reflected laser radiations at the air/shock-front and the shock-front/film interfaces.

Identification of nucleolus-localized PTEN and its function in regulating ribosome biogenesis.

The tumor suppressor PTEN is a lipid phosphatase that is found mutated in different types of human cancers. PTEN suppresses cell proliferation by inhibiting the PI3K-Akt signaling pathway at the cell membrane. However, PTEN is also demonstrated to localize in the cell nucleus where it exhibits tumor suppressive activity via a different, unknown mechanism. In this study we report that PTEN also localizes to the nucleolus and that nucleolar PTEN plays an important role in regulating nucleolar homeostasis and maintaining nucleolar morphology. Overexpression of nuclear PTEN in PTEN null cells inhibits Akt phosphorylation and reduces cell size. Knockdown of PTEN in PTEN positive cells leads to nucleolar morphologic changes and an increase in the proportion of cells with a greater number of nucleoli. In addition, knockdown of PTEN in PTEN positive cells increased ribosome biogenesis. These findings expand current understanding of function and relevance of nuclear localized PTEN and provide a foundation for the development of novel therapies targeting PTEN.

A Novel Five-Step Reduction Technique of Arytenoid Dislocation.

The article reported a novel reduction device and standardized reduction technique for patients with arytenoid dislocation. The results showed that this reduction technique has been excellent in helping patients with arytenoid dislocation. Laryngoscope, 134:1744-1748, 2024.

[Analysis of nasal flora composition in children with perennial allergic rhinitis].

Objective:This paper focuses on the diversity of nasal microbiota in children with perennial allergic rhinitis and the differences in species composition, which may be used in the future as a biomarker for disease progression and treatment. Methods:A total of 65 subjects were enrolled, including 35 perennial AR patients（AR group） and a Control group（CG group） of 30 children without AR. Collect basic information and examination reports of nasal swabs. 16S-rDNA high-throughput sequencing technology was used to detect the microbial sequence in nasal swabs, and the composition and difference of microbial diversity in each group were analyzed by bioinformatics methods. Results:The Simpson and Shannon index of the alpha diversity in the AR group had a significantly increase compared to the CG group. Beta diversity was not different between the groups. Staphylococcus（Firmicutes） of the AR group were significantly higher than that of the CG group, but Moraxella is lower than that of the CG group. Conclusion:Nasal microbial diversity and species composition of children with allergic rhinitis differ from those of healthy children, and how the differential microorganisms interact with the host and participate in immune regulation and inflammatory response requires further study.

Association of allergic rhinitis with persistent obstructive sleep apnea: A secondary analysis of the childhood adenotonsillectomy trial.

STUDY OBJECTIVES: Allergic rhinitis (AR) is frequently reported in children suffering from obstructive sleep apnea (OSA). This study aimed to assess whether children with AR are more likely to experience persistent OSA after AT. METHODS: This study is a secondary analysis of a multi-center randomized clinical trial, the Childhood Adenotonsillectomy Trial. Children were categorized into the AR group or Non-AR group according to AR response. A subgroup analysis was conducted using a logistic regression model. RESULTS: A total of 372 children (177 boys [47.6%]; median [IQR] age, 6.0 [5.0-8.0] years) were analyzed. Approximately 25% (93/372) of children presented with AR. Baseline data indicated higher PSQ scores and OSA-18 scores in the AR group. Children with AR demonstrated lower OSA resolution rates after AT (aOR, 0.43; 95% CI, 0.19 to 0.96). However, there was no significant difference in OSA resolution between the AR and Non-AR groups who underwent watchful waiting (aOR, 0.98; 95% CI, 0.50 to 1.93). Also, the AR group was more likely to maintain a PSQ score greater than 0.33 after AT (OR, 2.16; 95% CI, 1.01 to 4.61). There was no significant association between AR and higher follow-up OSA-18 scores after AT and watchful waiting. CONCLUSIONS: In this secondary analysis, children with AR were more likely to experience persistent OSA, highlighting the importance of effective AR management even post-adenotonsillectomy. A purposefully designed, prospective randomized trial is needed to verify the association between AR and persistent OSA. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00560859.

Global trends and hotspots on recurrent respiratory papillomatosis: A 20-year bibliometric analysis.

Objectives: Recurrent respiratory papillomatosis (RRP) is the most common benign laryngeal tumor in children. It can cause serious psychological and mental burden on patients since RRP requires repeated surgical treatment. This study aims to delineate the global trends and identify hotspots related to RRP over the past two decades. Methods: We systematically gathered research findings on RRP from 2004 to 2023, utilizing the Web of Science as our data source. Subsequently, we performed a comprehensive bibliometric analysis of the literature using Vosviewer, CiteSpace, and Bibliometrics online analysis platform. Results: A total of 839 publications were finally identified on RRP from 2004 to 2023. The United States has the largest number of publications (392), accounting for 46.7%. The Capital Medical University is the most productive organization (24), followed by the Centers for Disease Control and Prevention (18). The most productive journal was the Laryngoscope, with 86 publicatios. Comparatively, Vaccine is the most cited journal (2297). Craig S. Derkay ranked highest among all authors in publication (16). Burst detection shows onset, adjuvant therapy, management, juvenile-onset RRP, systemic bevacizumab, avastin, human papillomavirus vaccine are recent keywords of great interest to researchers. Conclusion: Research on RRP has progressed significantly over the past two decades, especially in terms of therapeutic strategies. We strongly believe that this article will provide new research directions for other researchers and may contribute to future breakthroughs in the field.

Bidirectional optical response hydrogel with adjustable human comfort temperature for smart windows.

Smart windows are effective in reducing the energy consumption of air conditioning and lighting systems, while contributing to maintaining the comfort zone of temperature in the indoor environment. Currently used smart windows mainly rely on traditional single-phase thermochromic material in which only one abrupt optical change occurs during temperature changes, and their inherent characteristics may not be suited for a practical balance of energy saving and privacy protection. Here, we developed a novel bidirectional optically responsive smart window (BSW) with unique bidirectional optical response features by introducing sodium dodecyl sulfate (SDS)/potassium tartrate (PTH) micelles into PNIPAM hydrogel to form a composite hydrogel, which was encapsulated in two glass panels. The upper critical solution temperature (UCST) and lowest critical solution temperature (LCST) of the material can be individually adjusted and are capable of matching the human comfort zone of temperature. In addition, the smart window exhibits remarkable transparency (92.5%), visible light transmission ratio (Tlum = 91.31%), and excellent solar modulation (ΔTsol,UCST = 76.34%, ΔTsol,LCST = 76.75%). Moreover, it possesses selectivity in transmitting light in the infrared band of solar radiation and can complete the "transparent-opaque" transition in a very narrow temperature range (<1 °C). When at comfortable temperatures, the highly transparent smart windows facilitate interior light and appreciation of the view. At low temperatures, SDS/PTH micelles aggregate to form large micelles, blocking the transmission of light and protecting customer privacy. At high temperatures, PNIPAM can undergo a "sol-gel" transition, thus blocking incident solar radiation. Taken together, these proposed materials with bidirectional optical response characteristics would be harnessed as a promising platform for building energy conservation, anti-counterfeiting, information encryption, and temperature monitoring.

Long-Term Follow-Up of a Case of Probable Aspergillus Skull Base Osteomyelitis With Galactomannan Test and Literature Review.

We report a probable case of Aspergillus basicranial infection diagnosed by pathogenic serological examination presenting atypical initial manifestations, and highlight the importance of serological examination to avoid treatment delay and disease management. An 84-year-old diabetic patient presented with right peripheral nerve palsy, intolerable otalgia, hearing loss, dysphagia, hoarseness, and bucking. The patient was diagnosed a probable Aspergillus skull base osteomyelitis with cranial neuritis and meningitis of central nervous system. Galactomannan test was used in combination with 1-3-ß-D-glucan and magnetic resonance imaging to follow-up during the continuous treatment of voriconazole. To date, the patient has remained in clinical remission for over 39 months but the drug cannot be stopped safely.

Surgical Management Strategies for Carotid Artery Invasion by Head and Neck Cancer: Ligation Versus Reconstruction.

OBJECTIVE: Whether ligation or reconstruction should be performed after radical resection of the tumor and carotid artery in patients with head and neck cancers invading the carotid artery (HNC-CA) has been controversial. This paper provides a review and meta-analysis of the efficacy of these 2 modalities. DATA SOURCES: PubMed, Cochrane, Web of Science, Scopus, and Ovid databases were searched through August 2023. REVIEW METHODS: Descriptive, graphical, tabular, and quantitative data were extracted. The statistical outcomes (risk difference, RD) were synthesized under a random-effects model. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guidelines. RESULTS: A total of 22 papers and 337 patients met the inclusion criteria for the literature review. Statistical analysis showed that the RD of overall survival (OS) rate at 1-year was 32% (95% confidence interval [CI]: 21%-42%) for ligation and 70% (95% CI: 65%-76%) for reconstruction (P < .05). The RD for OS rate at 2-year was 16% (95% CI: 7%-26%) for ligation and 39% (95% CI: 30%-47%) for reconstruction (P < .05). The RD for disease-free survival rate at 1-year was 27% (95% CI: 17%-38%) for ligation and 60% (95% CI: 51%-70%) for reconstruction (P < .05). There were no statistically significant differences (P > .05) between the 2 surgical modalities in terms of locoregional recurrence rate, carotid blowout rate, surgery-related complications rate, neurological complications rate, and perioperative mortality rate. CONCLUSION: This review demonstrates the significant advantage of carotid artery reconstruction surgery in short-term patient survival, thus making it a recommended option for HNC-CA patients undergoing radical surgery.

Application of covered stent implantation combined with radical tumor resection in advanced head and neck squamous cell carcinoma involving the carotid artery: a comparative study with historical literature.

BACKGROUND: Studies have shown that carotid artery reconstruction results in the best overall survival (OS) in Advanced Head and Neck Squamous Cell Carcinoma involving the Carotid Artery (AHNSCC-CA). AIMS: The purpose of this study was to evaluate the efficacy of covered stent implantation combined with radical tumor resection and to compare and analyze the historical literature on conventional carotid artery resection and reconstruction. MATERIALS AND METHODS: A total of 68 patients with AHNSCC-CA were included in this study. This study compared the survival, local recurrence, surgical complications, and neurologic complications between the two groups. RESULTS: The OS rate at 12 months in the experimental group was 58.5% (median survival time: 15 months, 95% CI: 7.61-22.40). The OS rate at 12 months in the control group was 34.3% (median survival time: 8 months, 95% CI: 3.94-12.06, p = .371). In addition, the differences in the rates of local recurrence, surgical complications and neurological complications between the two groups were statistically insignificant (p = .677, p = .197 and p = .617). CONCLUSIONS AND SIGNIFICANCE: Compared with conventional carotid artery resection and reconstruction, covered stent implantation combined with radical tumor resection yields similar survival outcomes, but with significantly lower surgical risk and difficulty, and faster postoperative recovery.

Quantifying Bevacizumab Efficacy in Recurrent Respiratory Papillomatosis.

OBJECTIVES: To develop and validate a novel method for quantifying the efficacy of Bevacizumab (Bev) in treating Recurrent Respiratory Papillomatosis (RRP), and to evaluate the clinical outcomes of a three-dose Bev induction therapy followed by surgical intervention. METHODS: Twenty-one RRP patients treated with a three-dose Bev regimen were included. A novel efficacy evaluation method using ImageJ software was developed to calculate the standardized lesion volume from laryngoscopic images. This was compared with the Derkay score. Clinical outcomes, including reduction rate, cumulative reduction rate, efficacy grading, recurrence, and adverse reactions, were analyzed. RESULTS: In the study cohort, the reduction rate was significantly higher after the first treatment compared with subsequent treatments. The overall response rate increased from 75% after the first treatment to 100% after the third. Among patients with localized lesions who underwent surgery, 76% experienced recurrence with a mean recurrence time of 114.23 days. Most recurrent lesions were smaller than at baseline. Adverse reactions included increased blood pressure in seven patients, which resolved without intervention. The new method showed a significant positive correlation with the Derkay score. CONCLUSION: In conclusion, based on the above findings, systemic Bev treatment for RRP is a safe and effective therapeutic approach, though further research is needed. Moreover, the new efficacy evaluation method we developed can significantly aid in studying the effectiveness of Bev treatment for RRP. LEVEL OF EVIDENCE: 2 Laryngoscope, 2024.