BackgroundGlioblastoma (GBM) is the most prominent and aggressive primary brain tumor in adults. Anoikis is a specific form of programmed cell death that plays a key role in tumor invasion and metastasis. The presence of anti-anoikis factors is associated with tumor aggressiveness and drug resistance.MethodsThe non-negative matrix factorization algorithm was used for effective dimension reduction for integrated datasets. Differences in the tumor microenvironment (TME), stemness indices, and clinical characteristics between the two clusters were analyzed. Difference analysis, weighted gene coexpression network analysis (WGCNA), univariate Cox regression, and least absolute shrinkage and selection operator regression were leveraged to screen prognosis-related genes and construct a risk score model. Immunohistochemistry was performed to evaluate the expression of representative genes in clinical specimens. The relationship between the risk score and the TME, stemness, clinical traits, and immunotherapy response was assessed in GBM and pancancer.ResultsTwo definite clusters were identified on the basis of anoikis-related gene expression. Patients with GBM assigned to C1 were characterized by shortened overall survival, higher suppressive immune infiltration levels, and lower stemness indices. We further constructed a risk scoring model to quantify the regulatory patterns of anoikis-related genes. The higher risk score group was characterized by a poor prognosis, the infiltration of suppressive immune cells and a differentiated phenotype, whereas the lower risk score group exhibited the opposite effects. In addition, patients in the lower risk score group exhibited a higher frequency of isocitrate dehydrogenase (IDH) mutations and a more sensitive response to immunotherapy. Drug sensitivity analysis was performed, revealing that the higher risk group may benefit more from drugs targeting the PI3K/mTOR signaling pathway.ConclusionWe revealed potential relationships between anoikis-related genes and clinical features, TME, stemness, IDH mutation, and immunotherapy and elucidated their therapeutic value.

Osteosarcoma (OS) is the most common primary malignant bone tumor in children and young adults and has a poor prognosis. Recent developments in the field of high-throughput sequencing technology, particularly in methylated RNA immunoprecipitation sequencing (MeRIP-seq), have led to renewed interest in RNA methylation. Among the various RNA modifications, N6-methyladenosine (m6A) modifications are the most common. Emerging evidence suggests that m6A methylation can affect the complexity of cancer progression by regulating biological functions related to cancer. In this review, we will shed light on recent findings regarding the biological function of m6A methylation in OS and discuss future research directions and potential clinical applications of RNA methyltransferases in OS.

Alzheimer's disease (AD) is a chronic neurological disease characterized by memory loss and progressive cognitive impairment. The characteristic AD pathologies include extracellular senile plaques formed by β-amyloid protein deposition, neurofibrillary tangles formed by hyper-phosphorylation of τ protein and neuronal loss caused by glial cell proliferation. However, the pathogenesis of AD is still unclear. Dysregulation of RNA methylation is associated with biological processes, including neurodevelopment and neurodegenerative disease. N6-methyladenosine (m6A) is the main modification in eukaryotic RNA and may be associated with the pathophysiology of AD. Circular RNA (circRNA) is a new type of evolutionarily conserved non-coding RNA without 5'-cap and 3'-polyadenylic acid tail. circRNA undergoes m6A RNA methylation and may be involved in the pathogenesis of AD. In the present study, high-throughput sequencing was performed to assess the degree of circRNA m6A methylation in APP/PS1 AD and C57BL/6 mice. These results suggested that circRNA m6A methylation in AD mice was markedly altered compared to the control group. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis was used to predict associated pathways; genes with different circRNA m6A methylation in AD mice were associated with 'axon guidance', 'long-term potentiation', 'glutamatergic synapse', 'cholinergic synapse', 'GABAergic synapse' and 'long-term depression'. Methylated RNA immunoprecipitation reverse transcription-quantitative PCR demonstrated that among the eight selected circRNA m6A genes, there were five genes that demonstrated significantly increased methylation and three demonstrated significantly decreased methylation.In summary, the present study indicated that circRNA m6A methylation may be associated with pathogenesis of AD.

Background and Aim. Irrecoverable anterior disc displacement (ADD) of temporomandibular joint (TMJ) seriously affects the quality of life of patients. This research was aimed to explore the recovery effect of small incision reduction and suture on patients. Methods. 90 patients with irreducible ADD of TMJ treated from August 2020 to August 2021 were acquired in our hospital. They were randomly divided into control group and trial group randomly. There were 45 patients in each group. The sufferers in the control group were treated with oral drug therapy and small incision reduction and suture, while those in the trial group were treated with small incision reduction and suture linked with functional appliance. The pain score, dysfunction, joint function recovery, facial improvement, and clinical impacts of the two groups were contrasted. Results. Compared with that in the control group at 1 week, 4 weeks, and 6 months after therapy, the pain score in the trial group was markedly higher. After therapy, in the two groups, maximum vertical opening (MVO), left lateral excursion (LLE), and right lateral excursion (RLE) levels were markedly higher than those in the control group. The MRI score of the trial group was markedly higher than that of the control group at 1 week, 4 weeks, and 6 months after therapy, and the total effective rate of the trial group was markedly higher than that of the control group. Conclusion. The use of small incision reduction and suture linked with functional appliance in the therapy of sufferers with irreducible ADD of TMJ is beneficial to relieve pain, promote the recovery of body function, and contribute to the recovery of joint function.

Background Glioblastoma (GBM) is the most malignant, aggressive and recurrent primary brain tumor. Cell senescence can cause irreversible cessation of cell division in normally proliferating cells. According to studies, senescence is a primary anti-tumor mechanism that may be seen in a variety of tumor types. It halts the growth and spread of tumors. Tumor suppressive functions held by cellular senescence provide new directions and pathways to promote cancer therapy. Methods We comprehensively analyzed the cell senescence-associated genes expression patterns. The potential molecular subtypes were acquired based on unsupervised cluster analysis. The tumor immune microenvironment (TME) variations, immune cell infiltration, and stemness index between 3 subtypes were analyzed. To identify genes linked with GBM prognosis and build a risk score model, we used weighted gene co-expression network analysis (WGCNA), univariate Cox regression, Least absolute shrinkage and selection operator regression (LASSO), and multivariate Cox regression analysis. And the correlation between risk scores and clinical traits, TME, GBM subtypes, as well as immunotherapy responses were estimated. Immunohistochemistry (IHC) and cellular experiments were performed to evaluate the expression and function of representative genes. Then the 2 risk scoring models were constructed based on the same method of calculation whose samples were acquired from the CGGA dataset and TCGA datasets to verify the rationality and the reliability of the risk scoring model. Finally, we conducted a pan-cancer analysis of the risk score, assessed drug sensitivity based on risk scores, and analyzed the pathways of sensitive drug action. Results The 3 potential molecular subtypes were acquired based on cell senescence-associated genes expression. The Log-rank test showed the difference in GBM patient survival between 3 potential molecular subtypes (P = 0.0027). Then, 11 cell senescence-associated genes were obtained to construct a risk-scoring model, which was systematically randomized to distinguish the train set (n = 293) and the test set (n = 292). The Kaplan-Meier (K-M) analyses indicated that the high-risk score in the train set (P < 0.0001), as well as the test set (P = 0.0053), corresponded with poorer survival. In addition, the high-risk score group showed a poor response to immunotherapy. The reliability and credibility of the risk scoring model were confirmed according to the CGGA dataset, TCGA datasets, and Pan-cancer analysis. According to drug sensitivity analysis, it was discovered that LJI308, a potent selective inhibitor of RSK pathways, has the highest drug sensitivity. Moreover, the GBM patients with higher risk scores may potentially be more beneficial from drugs that target cell cycle, mitosis, microtubule, DNA replication and apoptosis regulation signaling. Conclusion We identified potential associations between clinical characteristics, TME, stemness, subtypes, and immunotherapy, and we clarified the therapeutic usefulness of cell senescence-associated genes.

ObjectiveTo determine whether the inclusion of white blood cell (WBC) counts in the SYNTAX score (SS) or SS II models could improve the models’ performance for risk stratification in individuals with chronic renal insufficiency (CRI) following percutaneous coronary intervention (PCI).MethodsIn total, 2,313 patients with CRI, who were subjected to PCI and had data available on in-hospital WBC (ih-WBC) counts, were recruited. Patients were divided into 3 groups as per their ih-WBC counts (low, medium, and high). The primary endpoints were all-cause mortality (ACM) and cardiac mortality (CM). The secondary endpoints incorporated myocardial infarction, stroke, unplanned revascularization, and major adverse cardiovascular and cerebrovascular events (MACCEs).ResultsDuring a median follow-up of 3 years, the high WBC group had the highest incidences of CM (2.4% vs. 2.1% vs. 6.7%; p &lt; 0.001), ACM (6.3% vs. 4.1% vs. 8.2%; p &lt; 0.001), unplanned revascularization (8.4% vs. 12.4% vs. 14.1%; p &lt; 0.001), and MACCEs (19.3% vs. 23.0% vs. 29.2%; p &lt; 0.001) among the three groups. Multivariable Cox regression analysis depicted that the risk of ACM and CM in the high WBC group was 2.577 (95% confidence interval [CI]: 1.504–4.415, p &lt; 0.001) and 3.850 (95% CI: 1.835–8.080, p &lt; 0.001) times that in the low WBC group after adjusting for other confounding factors. A combination of ih-WBC counts with SS or SS II significantly improved the risk assessment and prediction of ACM and CM.ConclusionThe ih-WBC counts was associated with the risk of occurrence of ACM, CM, unplanned revascularization, and MACCEs in individuals with CRI following PCI. It provides an incremental predictive value for the occurrence of ACM and CM when included in SS or SS II models.

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ObjectiveThe study aimed to assess the correlation and agreement between resting full-cycle ratio (RFR) and fractional flow reserve (FFR), and evaluate the guiding value of a hybrid RFR-FFR strategy for percutaneous coronary intervention (PCI) in a Chinese real-world cohort with non-ST elevation acute coronary syndrome (NSTE-ACS).Materials and methodsA total of 109 patients with NSTE-ACS (149 diseased vessels), who underwent an invasive physiological assessment in Cangzhou Central Hospital, Hebei Medical University, were prospectively enrolled from September 2021 to May 2022. FFR ≤ 0.80 was used as the gold standard for coronary artery functional ischemia. We utilized the Pearson correlation and Bland-Altman analysis to assess the correlation and agreement between RFR and FFR. The diagnostic value of RFR predicting FFR ≤ 0.80 was evaluated in accordance with the receiver operating characteristic (ROC) curve. The hybrid RFR-FFR strategy, which was established according to determining the “gray zone” of RFR (FFR was further assessed using vasodilators only for diseased vessels in the “gray zone”), needed to afford over 95% global agreement with the FFR-only strategy.ResultsResting full-cycle ratio was significantly linearly linked with FFR (R2 = 0.636, P &lt; 0.001). The accuracy, specificity, and sensitivity for RFR ≤ 0.89 predicting FFR ≤ 0.80 were 81.2, 70.8, and 86.1%, respectively. The area under the ROC curve for RFR predicting FFR ≤ 0.80 was 0.881 (P &lt; 0.001), and the cutoff value was 0.90. The “gray zone” of RFR was 0.85–0.93. The positive and negative predictive values of the hybrid RFR-FFR strategy were 0.95 and 0.93, respectively. The hybrid RFR-FFR strategy exhibited an agreement of 96.0% with FFR and obviated the need for a vasodilator by 60.4%.ConclusionResting full-cycle ratio and FFR have high correlation and consistency. The hybrid RFR-FFR strategy highlights considerably enhanced agreement with the FFR-only strategy, whilst making the requirement of vasodilator administration less than a half.