Deciphering the tumor immune microenvironment from a multidimensional omics perspective: insight into next-generation CAR-T cell immunotherapy and beyond.

Tumor immune microenvironment (TIME) consists of intra-tumor immunological components and plays a significant role in tumor initiation, progression, metastasis, and response to therapy. Chimeric antigen receptor (CAR)-T cell immunotherapy has revolutionized the cancer treatment paradigm. Although CAR-T cell immunotherapy has emerged as a successful treatment for hematologic malignancies, it remains a conundrum for solid tumors. The heterogeneity of TIME is responsible for poor outcomes in CAR-T cell immunotherapy against solid tumors. The advancement of highly sophisticated technology enhances our exploration in TIME from a multi-omics perspective. In the era of machine learning, multi-omics studies could reveal the characteristics of TIME and its immune resistance mechanism. Therefore, the clinical efficacy of CAR-T cell immunotherapy in solid tumors could be further improved with strategies that target unfavorable conditions in TIME. Herein, this review seeks to investigate the factors influencing TIME formation and propose strategies for improving the effectiveness of CAR-T cell immunotherapy through a multi-omics perspective, with the ultimate goal of developing personalized therapeutic approaches.

Multi-omics analysis reveals that ferroptosis-related gene CISD2 is a prognostic biomarker of head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a prevalent malignancy, with high mortality rate and unavailability of accurate therapies. However, its early prevention remains a challenge. In the purview of predictive, preventive, and personalized medicine (PPPM), it is paramount to identify novel and powerful biomarkers. CISD2 is a crucial regulator of iron homeostasis and reactive oxygen species (ROS). Recent studies showed that the NEET protein (NAF-1) encoded by CISD2 is involved in regulating the proliferation and metastasis of tumor cells. Nevertheless, the prognostic value and immunological correlations of CISD2 remain unclear. METHODS: Bioinformatics analyses conducted utilizing data from comprehensive databases The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). All statistical evaluations were executed employing R software. RESULTS: Our investigation of biological function, enrichment pathway, and immune correlation revealed a discernable linkage between CISD2 and the immune response. Moreover, we found that the suppression of CISD2 is associated with immune cell infiltration and various immune signatures. CONCLUSIONS: The present study successfully revealed the potential prognostic and biological function of CISD2 in HNSCC. High expression of CISD2 are linked to gender, race, grade, etc., can notably enhance the early detection, prognosis, and prediction for individuals afflicted with HNSCC.

Disulfidptosis in head and neck squamous carcinoma: Integrative bioinformatic and in-vitro analysis.

BACKGROUND: Head and neck squamous carcinoma (HNSC) is a prevalent global malignancy with limited treatment options, which necessitates the development of novel therapeutic strategies. Disulfidptosis, a recently discovered and unique cell death pathway, may offer promise as a treatment target in HNSC. MATERIALS AND METHODS: We identified disulfidptosis-related genes (DRGs) using multiple algorithms and developed a prognostic model based on a disulfidptosis-related gene index (DRGI). The model's predictive accuracy was assessed by ROC-AUC, and patients were stratified by risk scores. We investigated the tumor immune microenvironment, immune responses, tumorigenesis pathways, and chemotherapy sensitivity (IC50). We also constructed a diagnostic model using 20 machine-learning algorithms and validated PCBP2 expression through RT-qPCR and western blot. RESULTS: We developed a 12-DRG DRGI prognostic model, classifying patients into high- and low-risk groups, with the high-risk group experiencing poorer clinical outcomes. Notable differences in tumor immune microenvironment and chemosensitivity were observed, with reduced immune activity and suboptimal treatment responses in the high-risk group. Advanced machine learning and in-vitro experiments supported DRGI's potential as a reliable HNSC diagnostic biomarker. CONCLUSION: We established a novel DRGI-based prognostic and diagnostic model for HNSC, exploring its tumor immune microenvironment implications, and offering valuable insights for future research and clinical trials.

Air pollution and skin diseases: A comprehensive evaluation of the associated mechanism.

Air pollutants deteriorate the survival environment and endanger human health around the world. A large number of studies have confirmed that air pollution jeopardizes multiple organs, such as the cardiovascular, respiratory, and central nervous systems. Skin is the largest organ and the first barrier that protects us from the outside world. Air pollutants such as particulate matter (PM), polycyclic aromatic hydrocarbons (PAHs), volatile organic compounds (VOCs) will affect the structure and function of the skin and bring about the development of inflammatory skin diseases (atopic dermatitis (AD), psoriasis), skin accessory diseases (acne, alopecia), auto-immune skin diseases (cutaneous lupus erythematosus(CLE) scleroderma), and even skin tumors (melanoma, basal cell carcinoma (BCC), squamous-cell carcinoma (SCC)). Oxidative stress, skin barrier damage, microbiome dysbiosis, and skin inflammation are the pathogenesis of air pollution stimulation. In this review, we summarize the current evidence on the effects of air pollution on skin diseases and possible mechanisms to provide strategies for future research.

F. Nucleatum enhances oral squamous cell carcinoma proliferation via E-cadherin/ß-Catenin pathway.

BACKGROUND: Fusobacterium nucleatum (F. nucleatum) is a microbial risk factor whose presence increases the risk of oral squamous cell carcinoma (OSCC) progression. However, whether it can promote the proliferation of OSCC cells remains unknown. METHODS: In this study, we investigated F. nucleatum effect on OSCC cell proliferation using in vitro and in vivo experiments. RESULTS: Our results showed that F. nucleatum promoted OSCC cell proliferation, doubling the cell count after 72 h (CCK-8 assay). Cell cycle analysis revealed G2/M phase arrest. F. nucleatum interaction with CDH1 triggered phosphorylation, upregulating downstream protein ß-catenin and activating cyclinD1 and Myc. Notably, F. nucleatum did not affect noncancerous cells, unrelated to CDH1 expression levels in CAL27 cells. Overexpression of phosphorylated CDH1 in 293T cells did not upregulate ß-catenin and cycle-related genes. In vivo BALB/c nude experiments showed increased tumor volume and Ki-67 proliferation index after F. nucleatum intervention. CONCLUSION: Our study suggests that F. nucleatum promotes OSCC cell proliferation through the CDH1/ß-catenin pathway, advancing our understanding of its role in OSCC progression and highlighting its potential as a therapeutic target.

Inflammatory cytokines mediating the effect of oral lichen planus on oral cavity cancer risk: a univariable and multivariable mendelian randomization study.

BACKGROUND: While observational studies and experimental data suggest a link between oral lichen planus (OLP) and oral cavity cancer (OCC), the causal relationship and the role of inflammatory cytokines remain unclear. METHODS: This study employed a univariable and multivariable Mendelian Randomization (MR) analysis to investigate the causal relationship between OLP and the risk of OCC. Additionally, the potential role of inflammatory cytokines in modulating this association was explored. Instrumental variables were derived from genetic variants associated with OLP (n = 377,277) identified in Finngen R9 datasets, with 41 inflammatory cytokines as potential mediators, and OCC (n = 4,151) as the outcome variable. Analytical methods including Inverse Variance Weighted (IVW), Weighted Median, MR-Egger, and MR-PRESSO were utilized to assess the causal links among OLP, inflammatory cytokines, and OCC risk. Multivariable MR (MVMR) was then applied to quantify the mediating effects of these cytokines in the relationship between OLP and increased OCC risk. RESULTS: MR analysis provided strong evidence of a causal relationship between OLP (OR = 1.417, 95% CI = 1.167-1.721, p < 0.001) and the risk of OCC. Furthermore, two inflammatory cytokines significantly influenced by OLP, IL-13 (OR = 1.088, 95% CI: 1.007-1.175, P = 0.032) and IL-9 (OR = 1.085, 95% CI: 1.005-1.171, P = 0.037), were identified. Subsequent analysis revealed a significant causal association only between IL-13 (OR = 1.408, 95% CI: 1.147-1.727, P = 0.001) and higher OCC risk, establishing it as a potential mediator. Further, MVMR analysis indicated that IL-13 (OR = 1.437, 95% CI = 1.139-1.815, P = 0.002) mediated the relationship between OLP and OCC, accounting for 8.13% of the mediation. CONCLUSION: This study not only elucidates the potential causal relationship between OLP and the risk of OCC but also highlights the pivotal mediating role of IL-13 in this association.

Oral microbiota may affect osteoradionecrosis following radiotherapy for head and neck cancer.

BACKGROUND: Osteoradionecrosis (ORN) is a serious complication of radiotherapy for head and neck cancer (HNC). However, its etiology and pathogenesis have not been completely elucidated. Recent studies suggest the involvement of the oral microbiota in the development of ORN. The aim of this study was to assess the correlation between oral microbiota and the extent of bone resorption in ORN patients. MATERIALS AND METHODS: Thirty patients who received high-dose radiotherapy for HNC were enrolled. Tissue specimens were collected from the unaffected and affected sides. The diversity, species differences and marker species of the oral microbial community were determined by 16 S rRNA sequencing and bioinformatics analysis. RESULTS: The ORN group had greater microbial abundance and species diversity. The relative abundance of f_Prevotellaceaeand, f_Fusobacteriaceae, f_Porphyromonadaceae, f_Actinomycetaceae, f_Staphylococcaceae, g_Prevotella, g_Staphylococcus, s_Endodontalis and s_Intermedia were particular;y increased in ORN, suggesting a potential association between the oral microbiota and ORN. Furthermore, g_Prevotella, g_Streptococcus, s_parvula and s_mucilaginosa were identified as potential diagnostic and prognostic biomarkers of ORN. Association network analysis also suggested an overall imbalance in species diversity and ecological diversity in the oral microbiota of ORN patients. In addition, pathway analysis indicated that the dominant microbiota in ORN may disrupt bone regeneration by regulating specific metabolic pathways that increase osteoclastic activity. CONCLUSION: Radiation-induced ORN is associated with significant changes in the oral microbiota, and the latter may play a potential role in the etiopathology of post-radiation ORN. The exact mechanisms through which the oral microbiota influence osteogenesis and osteoclastogenesis remain to be elucidated.

Halitosis: etiology, prevention, and the role of microbiota.

OBJECTIVES: This study aims to review halitosis research, discuss its various causes, and propose effective interventions based on the underlying etiologies and mechanisms. The main research question is to identify the primary factors contributing to halitosis and appropriate strategies to address them. MATERIALS AND METHODS: A comprehensive literature review was conducted on halitosis and its associated causes, including oral pathological factors, oral microbial influences, microbial metabolic pathways, gastrointestinal diseases, and gut microbiota dysbiosis. RESULTS: Unhealthy eating habits and an imbalance of microorganisms in the oral cavity and gastrointestinal tract were identified as primary causes of halitosis. Dental caries, periodontal disease, xerostomia, and digestive disorders like gastritis and irritable bowel syndrome were also found to be related to the development of halitosis. Due to poor oral hygiene or antibiotic use, disruption of microbial communities can result in dysbiosis, inflammation, and halitosis. CONCLUSIONS: Halitosis is a multifactorial condition with various underlying causes, including oral and systemic diseases. Effective interventions should be tailored based on the specific etiologies and mechanisms involved. CLINICAL RELEVANCE: Understanding the factors contributing to halitosis is crucial for developing appropriate treatment strategies. Enhancing oral hygiene habits, using antimicrobial drugs, or administering probiotics may help regulate oral or intestinal flora, thereby improving halitosis and overall oral health.

Network analysis reveals miRNA crosstalk between periodontitis and oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is one of the malignant tumors with a poor prognosis. Periodontitis (PD is considered a high-risk factor for OSCC, but the genetic mechanism is rarely studied. This study aims to link OSCC and PD by identifying common differentially expressed miRNAs (Co-DEmiRNAs), their related genes (Hub genes), transcription factors (TFs), signaling pathways, enrichment functions, and compounds, and searching for genetic commonalities. METHODS: The miRNAs expression datasets of OSCC and PD were searched from the GEO database. The miRNA and related crosstalk mechanism between OSCC and PD was obtained through a series of analyses. RESULTS: hsa-mir-497, hsa-mir-224, hsa-mir-210, hsa-mir-29c, hsa-mir-486-5p, and hsa-mir-31are the top miRNA nodes in Co-DEmiRNA-Target networks. The most significant candidate miRNA dysregulation genes are ZNF460, FBN1, CDK6, BTG2, and CBX6, while the most important dysregulation TF includes HIF1A, TP53, E2F1, MYCN, and JUN. 5-fluorouracil, Ginsenoside, Rh2, and Formaldehyde are the most correlated compounds. Enrichment analysis revealed cancer-related pathways and so on. CONCLUSIONS: The comprehensive analysis reveals the interacting genetic and molecular mechanism between OSCC and PD, linking both and providing a foundation for future basic and clinical research.

Brief literature review and comprehensive bioinformatics analytics unravel the potential mechanism of curcumin in the treatment of periodontitis.

OBJECTIVE: Periodontitis is a chronic oral disease prevalent worldwide, and natural products are recommended as adjunctive therapy due to their minor side effects. Curcumin, a widely used ancient compound, has been reported to possess therapeutic effects in periodontitis. However, the exact mechanism underlying its activity remains unclear. In this context, the present study aimed to conduct computational simulations to uncover the potential mechanism of action of Curcumin in the treatment of periodontitis. MATERIALS AND METHODS: Single-cell analysis was conducted using a dataset (i.e., GSE164241) curated from the Gene Expression Omnibus (GEO) database through an R package "Seurat package." Bulk RNA sequencing data were curated from GSE10334 and GSE16134 and processed by R package "Limma." Then, the marker genes in the single-cell transcriptome and differentially expressed genes (DEGs) in the bulk transcriptome were integrated. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were also carried out to reveal their functionalities. Key targets were mined from their protein-protein interaction (PPI) network topologically. Afterward, molecular docking was performed. The top-ranked pose was subjected to molecular dynamics simulations to investigate the stability of the docking result. RESULTS: FOS, CXCL1, CXCL8, and IL1B, were filtered after a series of selected processes. The results of molecular modeling suggested that except for IL1B, the Vena Scores of the rest exceeded -5 kcal/mol. Furthermore, the molecular dynamic simulation indicated that the binding of the CXCL8-Curcumin complex was stable over the entire 100 ns simulation. CONCLUSION: The present study unlocked the binding modes of CXCL1, FOS, and CXCL8 with the Curcumin molecule, which were relatively stable, especially for CXCL8, hindering its promising potential to serve as the critical targets of Curcumin in periodontitis treatment.

Bone Tumor Suppression in Rabbits by Hyperthermia below the Clinical Safety Limit Using Aligned Magnetic Bone Cement.

Demonstrating highly efficient alternating current (AC) magnetic field heating of nanoparticles in physiological environments under clinically safe field parameters has remained a great challenge, hindering clinical applications of magnetic hyperthermia. In this work, exceptionally high loss power of magnetic bone cement under the clinical safety limit of AC field parameters, incorporating direct current field-aligned soft magnetic Zn0.3 Fe2.7 O4 nanoparticles with low concentration, is reported. Under an AC field of 4 kA m-1 at 430 kHz, the aligned bone cement with 0.2 wt% nanoparticles achieves a temperature increase of 30 °C in 180 s. This amounts to a specific loss power value of 327 W gmetal-1 and an intrinsic loss power of 47 nHm2 kg-1 , which is enhanced by 50-fold compared to randomly oriented samples. The high-performance magnetic bone cement allows for the demonstration of effective hyperthermia suppression of tumor growth in the bone marrow cavity of New Zealand White Rabbits subjected to rapid cooling due to blood circulation, and significant enhancement of survival rate.

Role of the microbiome in oral cancer occurrence, progression and therapy.

The oral cavity, like other digestive or mucosal sites, contains a site-specific microbiome that plays a significant role in maintaining health and homeostasis. Strictly speaking, the gastrointestinal tract starts from the oral cavity, with special attention paid to the specific flora of the oral cavity. In healthy people, the microbiome of the oral microenvironment is governed by beneficial bacteria, that benefit the host by symbiosis. When a microecological imbalance occurs, changes in immune and metabolic signals affect the characteristics of cancer, as well as chronic inflammation, disruption of the epithelial barrier, changes in cell proliferation and cell apoptosis, genomic instability, angiogenesis, and epithelial barrier destruction and metabolic regulation. These pathophysiological changes could result in oral cancer. Rising evidence suggests that oral dysbacteriosis and particular microbes may play a positive role in the evolution, development, progression, and metastasis of oral cancer, for instance, oral squamous cell carcinoma (OSCC) through direct or indirect action.

MRE11 as a plausible biomarker and prognostic bioindicator for head and neck squamous cell carcinoma.

OBJECTIVE: Head and Neck Squamous Cell Carcinoma (HNSCC) ranks as the sixth most prevalent form of cancer worldwide. MRE11 protein contains multiple domains that play a role in the initiation of DNA repair. This study aimed to elucidate the expression and prognostic significance of MRE11 in HNSCC. MATERIAL AND METHODS: The Cancer Genome Atlas (TCGA-HNSCC) dataset comprising 520 HNSCC tissues and 44 normal tissues was initially used to evaluate the association between MRE11 expression and clinicopathologic characteristics. Kaplan-Meier plot was utilized for survival analysis. MRE11-immune cell interaction was analyzed using Tumor Immune Estimation Resource (TIMER) database. Further, Insilco methods were used to explore the protein network and its association with other pathways. Quantitative reverse transcription PCR (RT-qPCR) was used to validate the MRE11 mRNA expression in oral squamous cell carcinoma (OSCC) tissues in patient samples. RESULTS: MRE11 expression was upregulated in HNSCC, and the expression significantly varied across different clinical stages, pathological grades, and initial treatment outcomes. Further, high MRE11 expression is associated with poorer survival outcomes. MRE11 overexpression is also linked to the activation of the HIPPO signaling pathway, the mTOR signaling pathway, and the MYC/MYCN signaling pathway. CONCLUSION: MRE 11 can be considered a novel prognostic biomarker for HNSCC, which can be leveraged for promising treatment outcomes. This research highlights MRE11 as a novel molecular biomarker for HNSCC and offers a new direction for its treatment, explicitly targeting MRE11 and its network for therapeutic intervention.

Characterizing hedgehog pathway features in senescence associated osteoarthritis through Integrative multi-omics and machine learning analysis.

Purpose: Osteoarthritis (OA) is a disease of senescence and inflammation. Hedgehog's role in OA mechanisms is unclear. This study combines Bulk RNA-seq and scRNA-seq to identify Hedgehog-associated genes in OA, investigating their impact on the pathogenesis of OA. Materials and methods: Download and merge eight bulk-RNA seq datasets from GEO, also obtain a scRNA-seq dataset for validation and analysis. Analyze Hedgehog pathway activity in OA using bulk-RNA seq datasets. Use ten machine learning algorithms to identify important Hedgehog-associated genes, validate predictive models. Perform GSEA to investigate functional implications of identified Hedgehog-associated genes. Assess immune infiltration in OA using Cibersort and MCP-counter algorithms. Utilize ConsensusClusterPlus package to identify Hedgehog-related subgroups. Conduct WGCNA to identify key modules enriched based on Hedgehog-related subgroups. Characterization of genes by methylation and GWAS analysis. Evaluate Hedgehog pathway activity, expression of hub genes, pseudotime, and cell communication, in OA chondrocytes using scRNA-seq dataset. Validate Hedgehog-associated gene expression levels through Real-time PCR analysis. Results: The activity of the Hedgehog pathway is significantly enhanced in OA. Additionally, nine important Hedgehog-associated genes have been identified, and the predictive models built using these genes demonstrate strong predictive capabilities. GSEA analysis indicates a significant positive correlation between all seven important Hedgehog-associated genes and lysosomes. Consensus clustering reveals the presence of two hedgehog-related subgroups. In Cluster 1, Hedgehog pathway activity is significantly upregulated and associated with inflammatory pathways. WGCNA identifies that genes in the blue module are most significantly correlated with Cluster 1 and Cluster 2, as well as being involved in extracellular matrix and collagen-related pathways. Single-cell analysis confirms the significant upregulation of the Hedgehog pathway in OA, along with expression changes observed in 5 genes during putative temporal progression. Cell communication analysis suggests an association between low-scoring chondrocytes and macrophages. Conclusion: The Hedgehog pathway is significantly activated in OA and is associated with the extracellular matrix and collagen proteins. It plays a role in regulating immune cells and immune responses.

The underlying mechanism of chimeric antigen receptor (CAR)-T cell therapy triggering secondary T-cell cancers: Mystery of the Sphinx?

The U.S. Food and Drug Administration (FDA) has reported cases of T-cell malignancies, including CAR-positive lymphomas, in patients receiving B cell maturation antigen (BCMA)- or CD19-targeted autologous CAR-T cell immunotherapy. These reports were derived from clinical trials and/or post-marketing adverse event data. This finding has attracted widespread attention. Therefore, it is essential to explore the potential mechanisms by which chimeric antigen receptor (CAR)-T cell therapy triggers secondary T-cell cancers to further guarantee the safety of CAR-T cell therapy.

A Mendelian Randomisation Analysis Reveals No Relationship Between Periodontitis and Coronary Atherosclerosis.

OBJECTIVES: Growing evidence appears to intimate a profound connection between periodontitis and coronary atherosclerosis (CA), yet the existence of a causal relationship remains unclear. Through the implementation of Mendelian randomization analysis, we further evaluated the potential causal link between chronic/acute periodontitis (CP/AP) and CA. METHODS: Utilizing genome-wide association study (GWAS) summary statistics, we incorporated periodontitis data derived from European samples (n1 = 198,441; n2 = 195,762) and CA data from 61,194 cases. We conducted a 2 sample, bidirectional Mendelian randomization (MR) analysis using the inverse-variance weighted (IVW) method as the main analytical approach. Supplementary analyses were executed through MR Egger, Weighted median (WM), IVW, Simple mode, and Weighted mode approaches. RESULTS: The IVW analysis revealed no significant causal relationship between CA and periodontitis (CA-CP: OR = 2.110, 95% CI = 0.208-21.317, P = .527; CA-AP: OR = 0.414, 95% CI = 0.051-3.384, P = .644). Similarly, the bidirectional analysis did not identify impact of periodontitis on CA (OR = 1.000, 95% CI = 0.999-1.001, P = .953). The supplementary analyses corroborated these findings. CONCLUSIONS: While studies highlighting a correlation between periodontitis and CA, our comprehensive analysis does not corroborate a causal association between periodontitis and CA. Further research is needed to elucidate other potential shared mechanisms and causal evidence between periodontitis and CA.

Emerging role of immunogenic cell death in cancer immunotherapy: Advancing next-generation CAR-T cell immunotherapy by combination.

Immunogenic cell death (ICD) is a stress-driven form of regulated cell death (RCD) in which dying tumor cells' specific signaling pathways are activated to release damage-associated molecular patterns (DAMPs), leading to the robust anti-tumor immune response as well as a reversal of the tumor immune microenvironment from "cold" to "hot". Chimeric antigen receptor (CAR)-T cell therapy, as a landmark in anti-tumor immunotherapy, plays a formidable role in hematologic malignancies but falls short in solid tumors. The Gordian knot of CAR-T cells for solid tumors includes but is not limited to, tumor antigen heterogeneity or absence, physical and immune barriers of tumors. The combination of ICD induction therapy and CAR-T cell immunotherapy is expected to promote the intensive use of CAR-T cell in solid tumors. In this review, we summarize the characteristics of ICD, stress-responsive mechanism, and the synergistic effect of various ICD-based therapies with CAR-T cells to effectively improve anti-tumor capacity.

Interplay of Sphingolipid Metabolism in Predicting Prognosis of GBM Patients: Towards Precision Immunotherapy.

Background: In spite of numerous existing bio-surveillance systems for predicting glioma (GBM) prognosis, enhancing the efficacy of immunotherapy remains an ongoing conundrum. The continual scrutiny of the dynamic interplay between the sphingolipid metabolic pathway and tumor immunophenotypes has unveiled potential implications. However, the intricate orchestration of functional and regulatory mechanisms by long non-coding RNAs (lncRNAs) in GBM, particularly in the context of sphingolipid metabolism, remains cryptic. Methods: We harnessed established R packages to intersect gene expression profiles of GBM patients within the The Cancer Genome Atlas (TCGA) database with the compilation of sphingolipid metabolism genes from GeneCards. This enabled us to discern markedly distinct lncRNAs, which were subsequently deployed to construct a robust prognostic model utilizing Lasso-Cox regression analysis. We then scrutinized the immune microenvironment across various risk strata using the ssGSEA and CIBERSORT algorithms. To evaluate mutation patterns and drug resistance profiles within patient subgroups, we devised the "Prophytic" and "Maftools" packages, respectively. Results: Our investigation scrutinized lncRNAs linked to sphingolipid metabolism, utilizing glioma specimens from TCGA. We meticulously curated 1224 sphingolipid-associated genes gleaned from GeneCards and pinpointed 272 differentially expressed mRNAs via transcriptomic analysis. Enrichment analyses underscored their significance in sphingolipid processes. A prognostic model founded on 17 meticulously selected lncRNAs was systematically constructed and validated. This model adeptly stratified GBM patients into high- and low-risk categories, yielding highly precise prognostic insights. We also discerned correlations between immune cell infiltration and genetic mutation discrepancies, along with distinct therapeutic responses through drug sensitivity analysis. Notably, computational findings were corroborated through experimental validation by RT-PCR. Conclusion: In summation, our exhaustive inquiry underscores the multifaceted utility of the sphingolipid metabolic pathway as an autonomous diagnostic and prognostic indicator for glioma patients. Furthermore, we amalgamate a profusion of substantiated evidence concerning immune infiltration and gene mutations, thereby reinforcing the proposition that sphingolipid metabolism may function as a pivotal determinant in the panorama of immunotherapeutic interventions.

Molecular subtypes of ischemic heart disease based on circadian rhythm.

Coronary atherosclerotic heart disease (CAD) is among the most prevalent chronic diseases globally. Circadian rhythm disruption (CRD) is closely associated with the progression of various diseases. However, the precise role of CRD in the development of CAD remains to be elucidated. The Circadian rhythm disruption score (CRDscore) was employed to quantitatively assess the level of CRD in CAD samples. Our investigation revealed a significant association between high CRDscore and adverse prognosis in CAD patients, along with a substantial correlation with CAD progression. Remarkably distinct CRDscore distributions were also identified among various subtypes. In summary, we have pioneered the revelation of the relationship between CRD and CAD at the single-cell level and established reliable markers for the development, treatment, and prognosis of CAD. A deeper understanding of these mechanisms may offer new possibilities for incorporating "the therapy of coronary heart disease based circadian rhythm" into personalized medical treatment regimens.

MALT lymphoma of the head and neck: Surgery alone can be an option.

OBJECTIVES: To retrospectively analyze the general characteristics of MALT lymphoma in the head and neck and provide clinicians with new ideas for diagnosis and treatment. MATERIALS AND METHODS: 114 (94.2%) of 121 complete follow-up data were obtained. A single-center retrospective study was conducted on 114 patients with MALT diagnosed from 2010 to 2020. RESULTS: 42 (36.8%) of 114 patients had Sjogren's syndrome before, and there is a significant difference in gender between SS-MALT and non-SS-MALT. As for the treatment method, there is no significant difference in the overall survival between surgery with or without chemoradiotherapy. CONCLUSION: MALT lymphoma of the head and neck is clinically characterized by a favorable prognosis, always associated with SS. Surgery with or without chemoradiotherapy has little difference in the prolongation of survival time.