The prognostic value of ubiquitin/ubiquitin-like-related genes along with immune cell infiltration and clinicopathological features in osteosarcoma.

BACKGROUND: Ubiquitin/ubiquitin-like (Ub/UBL)-related genes have been reported to be associated with the survival of osteosarcoma patients but have not yet been systematically explored. METHODS: The prognostic value of Ub/UBL-related genes, immune cell infiltration and clinicopathological features of patients were explored by Cox and LASSO regression analyses. A prognostic model was established and then validated in the GSE21257 dataset. The differential expression of hub genes in osteosarcoma was confirmed by qRT-PCR, western blotting and immunohistochemistry. RESULTS: Tripartite Motif Containing 8 (TRIM8) and Ubiquitin Like With PHD And Ring Finger Domains 2 (UHRF2) were screened as genes with prognostic value in osteosarcoma. Kaplan-Meier analysis and scatter plots indicated that patients in the high gene significance score group tended to have a worse prognosis. The concordance index, calibration analysis and receiver operating characteristic analysis suggested that the model had good prediction accuracy and high sensitivity and specificity. Decision curve analysis revealed that patients could obtain greater net benefit from this model. Functional analyses of the differentially expressed genes indicated that they were involved in important functions and pathways. TRIM8 and UHRF2 were confirmed to be highly expressed in osteosarcoma cell lines and tissues. CONCLUSIONS: TRIM8 and UHRF2 are potential prognostic genes in osteosarcoma, and these results provide insights into the roles of these genes and their implications for patient outcomes.

Prognostic value of PRR11 and immune cell infiltration in Ewing sarcoma.

Ewing's sarcoma (ES) is the second most common bone and soft tissue malignancy in children and adolescents with a poor prognosis. The identification of genes with prognostic value may contribute to the prediction and treatment of this disease. The GSE17679, GSE68776, GSE63155, and GSE63156 datasets were downloaded from the Gene Expression Omnibus database and qualified. Prognostic value of differentially expressed genes (DEGs) between the normal and tumor groups and immune cell infiltration were explored by several algorithms. A prognostic model was established and validated. Finally, functional analyses of the DEGs were performed. Proline rich 11 (PRR11) and mast cell infiltration were noted as the key indicators for the prognosis of ES. Kaplan-Meier and scatter plots for the training and two validation sets showed that patients in the low-PRR11 expression group were associated with better outcomes than those in the high-PRR11 expression group. The concordance indices and calibration analyses of the prognostic model indicated good predictive accuracy in the training and validation sets. The area under the curve values obtained through the receiver operating characteristic analysis for 1-, 3-, 5-year prediction were ≥ 0.75 in the three cohorts, suggesting satisfactory sensitivity and specificity of the model. Decision curve analyses suggested that patients could benefit more from the model than the other strategies. Functional analyses suggested that DEGs were mainly clustered in the cell cycle pathway. PRR11 and mast cell infiltration are potential prognostic indicators in ES. PRR11 possibly affects the prognosis of patients with ES through the cell cycle pathway.

Prognostic value of GLCE and infiltrating immune cells in Ewing sarcoma.

Background: The prognostic value of D-glucuronyl C5-epimerase (GLCE) and mast cell infiltration in Ewing sarcoma (ES) has not been well specified and highlighted, which may facilitate survival prediction and treatment. Methods: Several qualified datasets were downloaded from the GEO website. Common differentially expressed genes between normal subjects and ES patients in GSE17679, GSE45544, and GSE68776 were identified and screened by multiple algorithms to find hub genes with prognostic value. The prognostic value of 64 infiltrating cells was also explored. A prognostic model was established and then validated with GSE63155 and GSE63156. Finally, functional analysis was performed. Results: GLCE and mast cell infiltration were screened as two indicators for a prognostic model. The Kaplan‒Meier analysis showed that patients in the low GLCE expression, mast cell infiltration and risk score groups had poorer outcomes than patients in the high GLCE expression, mast cell infiltration and risk score groups, both in the training and validation sets. Scatter plots and heatmaps also indicated the same results. The concordance indices and calibration analyses indicated a high prediction accuracy of the model in the training and validation sets. The time-dependent receiver operating characteristic analyses suggested high sensitivity and specificity of the model, with area under the curve values between 0.76 and 0.98. The decision curve analyses suggested a significantly higher net benefit by the model than the treat-all and treat-none strategies. Functional analyses suggested that glycosaminoglycan biosynthesis-heparan sulfate/heparin, the cell cycle and microRNAs in cancer were upregulated in ES patients. Conclusions: GLCE and mast cell infiltration are potential prognostic indicators in ES. GLCE may affect the proliferation, angiogenesis and metastasis of ES by affecting the biosynthesis of heparan sulfate and heparin.

Efficacy and safety of CM310 in severe eosinophilic chronic rhinosinusitis with nasal polyps (CROWNS-1): a multicentre, randomised, double-blind, placebo-controlled phase 2 clinical trial.

Background: Severe eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) remains the most relapsed subtype of uncontrolled CRSwNP. CM310, a humanised anti-interleukin (IL)-4 receptor alpha monoclonal antibody, inhibits IL-4 and IL-13 signaling which underlying eosinophilic inflammation. This study aims to evaluate the efficacy and safety of CM310 in patients with severe ECRSwNP. Methods: A multicentre, randomised, double-blind, and placebo-controlled phase 2 clinical trial was conducted. 56 eligible adult patients with severe ECRSwNP were randomised 1:1 to receive subcutaneously either CM310 (300 mg) or placebo every 2 weeks under the background therapy of mometasone furoate nasal spray (MFNS) for 16 weeks, with 8 weeks of follow-up. Coprimary endpoints included the changes from baseline in nasal polyp score (NPS) and nasal congestion score (NCS) at week 16. Key secondary endpoints included sinus Lund-Mackay CT score, change in sinus volume occupied by disease, University of Pennsylvania Smell Identification Test score, 22-item Sino-nasal Outcome Test score, and total symptom score. Safety, pharmacodynamics, and changes in type 2 inflammation biomarkers were assessed. This study is registered with ClinicalTrials.gov, NCT04805398. Findings: Between April 6, 2021, and March 18, 2022, 27 patients respectively in both the CM310 and placebo groups completed the study. Findings suggested that CM310 improved the coprimary efficacy endpoints of decreasing nasal polyp size and alleviating nasal congestion compared with the placebo. Least squares (LS) mean differences (CM310 vs placebo) of change from baseline in NPS and NCS at week 16 were -2.1 (95% CI -2.9, -1.4; p < 0.0001) and -0.9 (95% CI -1.4, -0.5; p < 0.0001), respectively. Sinus CT scan revealed that Lund-Mackay CT score (LS mean difference [95% CI] -7.6, [-9.4, -5.8]; p < 0.0001) and sinus volume occupied by disease (LS mean difference [95% CI] -37%, [-47%, -28%]; p < 0.0001) were significantly improved with CM310 compared with placebo. In addition, CM310 significantly relieved the daily symptoms of patients with CRSwNP and improved their quality of life reflected by the improvements in the TSS (-2.6 [95% CI -3.5, -1.6]), UPSIT (10.4 [95% CI 6.8, 14.0]) and SNOT-22 score (-19.1 [95% CI -29.8, -8.5]). Compared with placebo, CM310 administration significantly reduced type 2-related biomarkers including the serum TARC and total IgE, and tissue eosinophils. The most common adverse events were upper respiratory tract infection, blood cholesterol increased, and tinnitus, but none were considered drug-related. Interpretation: These findings support CM310 as an effective additional treatment option to the standard of care in patients with severe ECRSwNP. Funding: KeyMed Biosciences (Chengdu) Limited.

The prognostic value of autophagy related genes with potential protective function in Ewing sarcoma.

BACKGROUND: Ewing sarcoma (ES) is the second most common primary malignant bone tumor mainly occurring in children, adolescents and young adults with high metastasis and mortality. Autophagy has been reported to be involved in the survival of ES, but the role remains unclear. Therefore, it's necessary to investigate the prognostic value of autophagy related genes using bioinformatics methods. RESULTS: ATG2B, ATG10 and DAPK1 were final screened genes for a prognostic model. KM and risk score plots showed patients in high score group had better prognoses both in training and validation sets. C-indexes of the model for training and validation sets were 0.68 and 0.71, respectively. Calibration analyses indicated the model had high prediction accuracy in training and validation sets. The AUC values of ROC for 1-, 3-, 5-year prediction were 0.65, 0.73 and 0.84 in training set, 0.88, 0.73 and 0.79 in validation set, which suggested high prediction accuracy of the model. Decision curve analyses showed that patients could benefit much from the model. Differential and functional analyses suggested that autophagy and apoptosis were upregulated in high risk score group. CONCLUSIONS: ATG2B, ATG10 and DAPK1 were autophagy related genes with potential protective function in ES. The prognostic model established by them exhibited excellent prediction accuracy and discriminatory capacities. They might be used as potential prognostic biomarkers and therapeutic targets in ES.

A longitudinally expanded Ni-based metal-organic framework with enhanced double nickel cation catalysis reaction channels for a non-enzymatic sweat glucose biosensor.

Nickel-based metal-organic frameworks (Ni-MOFs) have attracted increasing attention in non-enzymatic glucose sensing. However, the insufficient active Ni cation sites from a stacked MOF layer, the unclear Ni catalysis mechanism, and the severe liquid alkaline electrolyte remain challenging for practical applications. In this work, the sonication-induced longitudinal-expansion of Ni-MOFs increases the active nickel ion sites, which not only enhances the current response to glucose detection, but also shows the oxidation peak evolution of nickel ions with different sonication times, revealing the mechanism of different glucose detection channels. The Ni-MOF sonicated for 60 min (60 min Ni-MOF) displays enhanced Ni(iii)/Ni(ii) and more significant Ni(iv)/Ni(iii) double nickel cation channels for catalyzing glucose into glucolactone compared to the 0 min Ni-MOF (without sonication), showing optimized glucose detection ability with a high sensitivity of 3297.10 µA mM-1 cm-2, a low detection limit of ∼8.97 µM (signal-to-noise = 3) and a wide linear response range from 10 to 400 µM from the cyclic voltammetry test as well as a high sensitivity of 3.03 µA mM-1 cm-2, a low detection limit of ∼1.16 µM (signal-to-noise = 3) and a wide linear response range from 10 to 2000 µM from the chronoamperometry test. More importantly, an all-solid-state glucose biosensor using a PVA/NaOH solid-state electrolyte and a disposable 60 min Ni-MOF working electrode is assembled for non-enzymatic sweat glucose detection.

The Evi5 oncogene promotes laryngeal cancer cells proliferation by stabilizing c-Myc protein.

BACKGROUND: The Ecotropic viral integration site 5 (Evi5) is recognized as a potential oncogene and a cell cycle regulator. Evi5 regulates the abundance of Emi1, an inhibitor of the anaphase-promoting complex/cyclosome, to govern mitotic fidelity. Evi5 has been shown to be dysregulated in several cancer types. However, the expression and biological function of Evi5 in human laryngeal squamous cell carcinoma (LSCC) are still unknown. METHODS: Clustered regularly interspaced short palindromic repeats (CRISPR)-based gene editing was used to generate Evi5 knockout (KO) LSCC cells. The proliferation and cell cycle distribution of LSCC cells was determined. The effect of Evi5 on LSCC tumor growth in vivo was studied in a tumor xenograft model in mice. The interaction between Evi5 and c-Myc was detected by immunoprecipitation (IP) assay. Luciferase assay was used to determine the transcriptional activity of c-Myc. RESULTS: Here, we show that Evi5 controls LSCC tumorigenesis via the stabilization of c-MYC oncogene. CRISPR-mediated knockout (KO) of Evi5 decreased the proliferation and decreased colony formation ability of LSCC cells. Knockout of Evi5 caused increased G1 phase and decreased S phase cells. In the tumor-bearing nude mice, The transplanted tumors originated from Evi5-KO TU212 cells were significantly decreased when compared with control TU212 cells. At the molecular level, we found that Evi5 interacted with c-MYC and Evi5 antagonized E3 ligase FBXW7-mediated ubiquitination and degradation of c-Myc protein, and promoted c-Myc-dependent transactivation. CONCLUSION: Given the critical role of c-Myc in tumorigenesis, our data suggest that Evi5 is a potential therapeutic target in LSCC, and inhibition of Evi5 should be a prospective strategy for LSCC therapy.

[Application of nasal endoscopy in styloid process truncating operation].

OBJECTIVE: To investigate the application and the clinical effect of nasal endoscope in styloid process truncating operation. METHOD: Dividing 66 patients into nasal endoscope group and control group randomly, and then observe them. Nasal endoscope group were cured with nasal endoscope during the styloid process truncating operation and the control group were treated with the routine method of intraoral path. All the operations were executed by the same person. Observation index included the following aspects: the length of the truncated styloid process, the operation time, intraoperative bleeding, postoperative pain and pain degree, inflammatory reaction of raw surface and rehaemorrhagia. RESULT: Compared with the control group, the length of the truncated styloid process of nasal endoscope group were longer and the operation time had no significant differences. The intraoperative bleeding of intraoperative bleeding group were (85.0 +/- 35.0)ml and in control group were (95.0 +/- 40.0)ml. There are no significant differences between the result. Nasal endoscope group also had the advantages of fewer aches and less inflammatory reaction of raw surface. Both of the team had no rehaemorrhagia. CONCLUSION: nasal endoscope can truncate a longer styloid process in styloid process truncating operation and is effective to relieve pain, and ease inflammatory reaction, it's a safe mini-trauma operation.

[A case report of isolated marginal zone B cell lymphoma originating from the parapharyngeal space].

This is a case report of isolated marginal zone B cell lymphoma originating from the parapharyngeal space and reaching up to the side of skull base. There are no obvious clinical symptoms of the marginal zone B cell lymphoma originating in the parapharyngeal space, the imaging examination of which showed slightly blurred edge mass shadow with heterogeneous textures and no specificity. The pathological examination revealed a large number of lymphocyte proliferation, which was not specific yet. Immunohistochemistry may show the tumor was monoclonal and positive to CD20 and CD79a positive. Marginal zone B cell lymphoma originating in the parapharyngeal space is a rare tumor with no specific clinical symptoms or early signs, and is easily misdiagnosed. The diagnosis should be confirmed based on pathological and immunohistochemical examination, and the tumor can be treated by surgery combined with chemotherapy.

Indole-3-carbinol inhibits nasopharyngeal carcinoma cell growth in vivo and in vitro through inhibition of the PI3K/Akt pathway.

Indole-3-carbinol (I3C) is an active component of cruciferous vegetables and has been shown to markedly inhibit the growth of a variety of tumors. However, the role of I3C in nasopharyngeal carcinoma (NPC) remains unclear. Thus, the aim of the present study was to investigate the inhibition of NPC cells by I3C in vitro and in vivo. The human CNE2 NPC cell line was treated with various concentrations (0, 100, 200 and 300 µM) of I3C and analysis of cell proliferation after 0, 24, 48 and 72 h, apoptosis after 48 h and expression levels of phosphatidylinositol 3-kinase (PI3K)/Akt pathway-associated proteins in vitro was performed. BALB/c nude mice were divided into the following groups: Prevention, treatment and control. In vivo, all the nude mice were inoculated with CNE2 NPC cells and the mice in the prevention and treatment groups were administered a diet containing 0.5% I3C prior to and following inoculation, respectively. The tumoricidal effect of I3C was investigated in the nude mice. After eight weeks, the expression levels of PI3K/Akt pathway-associated proteins were analyzed in the tumors from the nude mice in each group. The results demonstrated that with increasing I3C concentrations, cell proliferation decreased and apoptosis increased significantly. In addition, the expression levels of PI3K/Akt pathway-associated proteins decreased. In the animal experiments, the prevention and treatment groups developed smaller tumors and the expression levels of PI3K/Akt pathway-associated proteins were reduced when compared with those in the control group. In addition, very few changes to the heart, liver and kidney tissues were observed with hematoxylin and eosin staining in all the groups. Therefore, the results of the present study indicated that I3C inhibited the growth of NPC cells and induced apoptosis effectively in vivo and in vitro. The underlying mechanism may be that I3C suppresses the PI3K/Akt pathway.

The efficacy of traditional Chinese Medicine as an adjunctive therapy in nasopharyngeal carcinoma: a systematic review and meta-analysis.

PURPOSE: The purpose of this systematic review was to assess the efficacy of traditional Chinese Medicine (TCM) as an adjunctive therapy to radiotherapy (RT) and/or chemotherapy (CT) for patients with nasopharyngeal carcinoma (NPC). METHODS: Randomized controlled trials (RCTs) with TCM to treat NPC were extensively searched in eight databases. Two researchers independently assessed the quality and validity of the included trials and extracted outcome data. Thirteen RCTs were included for analysis. RESULTS: Compared to using RT and/or CT, TCM combined with conventional cancer therapy had significantly improved Karnofsky performance status (KPS) [odds ratio (OR) 4.81, 95% confidence interval (CI) 3.06-7.56]. TCM as an adjunctive therapy significantly reduced the serious adverse effects of RT to the oral mucosa and skin so that grade I+II prevailed [OR 2.19, 95% CI 1.31-3.66; OR 8.63, 95% CI 3.28-22.70, respectively]. The combined therapy significantly enhanced immunoregulation, improving the levels of CD3, CD4 T cells (OR 10.08, 95% CI 1.38-18.78; OR 7.08, 95% CI 2.41-11.74, respectively). CONCLUSIONS: This systematic review suggests that TCM as a therapy adjunctive to RT and/or CT vs only RT and/ or CT has significant efficacy in terms of improvement of quality of life (QoL), alleviation of acute adverse effects, and enhancement of immunoregulation.