m6A Regulator-Based Methylation Modification Patterns Characterized by Distinct Tumor Microenvironment Immune Profiles in Rectal Cancer.

Background: Previous studies reported the related role of RNA n6-methyladenosine (m6A) modification in tumorigenesis and development. However, it is not clear whether m6A modification also plays a potential role in the immune regulation of rectal cancer (RC) and the formation of tumor microenvironment. Methods: In this study, we screened 23 m6A regulatory factors from 369 rectal cancer specimens, further determined the modification patterns of m6A in RC, and systematically linked these modification patterns with the characteristics of TME cell infiltration. The principal component analysis (PCA) algorithm was used to evaluate the m6A modification pattern of a single tumor related to immune response. Results: Three different m6A modification patterns were found in the measurement results, which are related to different clinical results and biological pathways. TME identification results show that the identified m6A pattern is closely related to immune characteristics. According to the m6Ascore extracted from m6A-related signature genes, RC patients were divided into high and low score subgroups combined with tumor mutation burden. Patients with high tumor mutation burden and higher m6Ascore have a significant survival advantage and enhanced immune infiltration. Further analysis showed that patients with higher m6Ascore had higher PD-L1 expression levels and showed better immune response and lasting clinical benefits. Conclusions: M6A modification plays a crucial role in the formation of TME diversity and complexity. The evaluation of the m6A modification mode will help us to enhance our understanding of the characteristics of TME infiltration and provide new insights for more effective immunotherapy strategies.

Surgery Treatment of Primary Tumors of the Inferior Vena Cava.

Background: Primary tumor of the inferior vena cava is a rare tumor, which arises from the smooth muscle of vascular walls. Surgery appears the only curative treatment. However, the optimal surgical methods and surgical management are not well-studied. In this article, we reviewed the successful treatment experience of patients in our center who had resection of primary tumor of the inferior vena cava and reviewed the relevant literature. Methods: Four cases of patients who undergoing initial resection of primary tumors of the inferior vena cava from September 2017 to August 2021 in the Second Affiliated Hospital of Nanchang University were screened and followed up. They were discussed and cases reported in this field were reviewed. Results: Among the four patients, three of them were female. The median age of the disease is 53.75 years (range 45-60 years). After surgical treatment, tumors were removed in all patients, and some patients had reconstruction of inferior vena cava. There were no disease-specific deaths, no serious complications, and no recurrence during follow-up in these cases. Conclusions: Careful preoperative examination, correct surgical treatment methods, and multidisciplinary collaboration can lead to safe and successful operations, which improve the survival rate of patients.

Chronic low-grade inflammation is involved in TLR4 knockout-induced spontaneous obesity in aged mice.

Chronic inflammation plays an important role in obesity-related complications, including insulin resistance, type 2 diabetes, and cardiovascular disease. The imbalances between T helper (Th)1/Th2 cells and Th17/regulatory T (Treg) cells participate in the pathogenesis of inflammation. Previously it was demonstrated that Toll-like receptor (TLR) 4 knockout (KO) prevents high-fat diet (HFD)-induced obesity of young mice (6 months of age), however the effect of TLR4 KO on spontaneous obesity in aged mice (18 month of age) is still unknown. To further study this, TLR4 KO and WT mice were fed with a standard chow diet from weaning to the endpoint of the experiment. We found that TLR4-/- mice were thinner compared with WT mice at 6 months (M) old. However, TLR4-/- mice spontaneously developed obesity with increased weight and adiposity in both subcutaneous and visceral fat depots by 18 M old. Our results also indicated that TLR4 KO activated TRIF/IRF3 signalling, induced inflammation, and repolarised alternatively-activated (M2) macrophages to classically-activated (M1) macrophages. In addition, TLR4 KO resulted in an increased spleen index and induced imbalances of Th1/Th2 and Th17/Treg cells which indicated the occurrence of chronic low-grade inflammation. In conclusion, chronic low-grade inflammation induced by TLR4 KO was involved in spontaneous obesity in aged mice. An emerging link was established among the TRIF/IRF3 pathway, chronic low-grade inflammation, and obesity. We hope that these novel findings will provide a potential preventive strategy for obesity and build a spontaneous obesity mouse model.

Construction of a prognostic assessment model for colon cancer patients based on immune-related genes and exploration of related immune characteristics.

Objectives: To establish a novel risk score model that could predict the survival and immune response of patients with colon cancer. Methods: We used The Cancer Genome Atlas (TCGA) database to get mRNA expression profile data, corresponding clinical information and somatic mutation data of patients with colon cancer. Limma R software package and univariate Cox regression were performed to screen out immune-related prognostic genes. GO (Gene ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) were used for gene function enrichment analysis. The risk scoring model was established by Lasso regression and multivariate Cox regression. CIBERSORT was conducted to estimate 22 types of tumor-infiltrating immune cells and immune cell functions in tumors. Correlation analysis was used to demonstrate the relationship between the risk score and immune escape potential. Results: 679 immune-related genes were selected from 7846 differentially expressed genes (DEGs). GO and KEGG analysis found that immune-related DEGs were mainly enriched in immune response, complement activation, cytokine-cytokine receptor interaction and so on. Finally, we established a 3 immune-related genes risk scoring model, which was the accurate independent predictor of overall survival (OS) in colon cancer. Correlation analysis indicated that there were significant differences in T cell exclusion potential in low-risk and high-risk groups. Conclusion: The immune-related gene risk scoring model could contribute to predicting the clinical outcome of patients with colon cancer.

Aberrance of Zinc Metalloenzymes-Induced Human Diseases and Its Potential Mechanisms.

Zinc, an essential micronutrient in the human body, is a component in over 300 enzymes and participates in regulating enzymatic activity. Zinc metalloenzymes play a crucial role in physiological processes including antioxidant, anti-inflammatory, and immune responses, as well as apoptosis. Aberrant enzyme activity can lead to various human diseases. In this review, we summarize zinc homeostasis, the roles of zinc in zinc metalloenzymes, the physiological processes of zinc metalloenzymes, and aberrant zinc metalloenzymes in human diseases. In addition, potential mechanisms of action are also discussed. This comprehensive understanding of the mechanisms of action of the regulatory functions of zinc in enzyme activity could inform novel zinc-micronutrient-supply strategies for the treatment of diseases.

Exploring the Potential Molecular Mechanism of Scutellaria baicalensis Georgi in the Treatment of Gastric Cancer Based on Network Pharmacological Analysis and Molecular Docking Technology.

Objective: To explore the molecular mechanism of Scutellaria baicalensis Georgi in treating gastric cancer by network pharmacological analysis and molecular docking. Methods: Taking Scutellaria baicalensis Georgi as the object, the active components and corresponding potential drug targets in Scutellaria baicalensis Georgi were obtained from the database of TCM Pharmacological System Analysis Platform (TCMSP). GeneCards/OMIM/DrugBank and other databases were used to collect gastric cancer-related genes, and the obtained genes were intersected with drug targets to obtain the target genes of Scutellaria baicalensis Georgi on gastric cancer. Furthermore, the interaction network of Scutellaria baicalensis Georgi-active ingredients-target-gastric cancer-related genes was constructed. Protein-protein interaction analysis and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on target genes. The PubChem website was used to screen the compounds corresponding to the target genes, and the target protein and 3D structure pdb format files were obtained from the PDB database. Finally, the molecular docking calculation was performed by the AutoDock Vina program. The in vivo cell experiments on the effect of Scutellaria baicalensis on proliferation and migration of gastric cancer cells were used to determine the therapeutic effect of Scutellaria baicalensis on gastric cancer, and the two genes ESR1 and FOS are the key targets of Scutellaria baicalensis on gastric cancer. Results: A total of 10 gastric cancer-related target genes were screened out, and Scutellaria baicalensis Georgi contained 10 active compounds targeting 10 gene sites. There are 30 effective compounds in Scutellaria baicalensis Georgi targeted to treat gastric cancer, and there are 91 corresponding targeting gene sites, involving a total of 10 pathways. The results of molecular docking show that ESR1, FOS, and Scutellaria baicalensis Georgi have good binding free energy and docking fraction. The docking fraction of FOS is -4.200 and the binding free energy is -27.893 kcal/mol. The docking fraction of ESR1 is -5.833 and the binding free energy is -30.001 kcal/mol. The effect of Scutellaria baicalensis Georgi on gastric cancer was verified by in vitro cell experiments and Western blotting. Conclusion: Scutellaria baicalensis Georgi can target and regulate multiple signal pathways by acting on ESR1 and FOS gene loci, thus having a potential therapeutic effect on gastric cancer.

Risk Analysis of Severe Thrombocytopenia in Nasopharyngeal Carcinoma During Concurrent Radio-Chemotherapy.

OBJECTIVE: To explore the risk factors and predictive indexes of severe thrombocytopenia during concurrent radio-chemotherapy of nasopharyngeal carcinomas. METHODS: Retrospective analysis was performed from the hospitalized patients with nasopharyngeal carcinoma from August 2014 to July 2017, and induction chemotherapy and concurrent radio-chemotherapy were completed. According to the lowest platelet count during concurrent chemotherapy, patients were divided into observation and control groups. General information and laboratory examinations were recorded and analyzed by univariate analysis, multivariate regression analysis, and ROC curve analysis. RESULTS: Factors, including age, PLT, IBIL, APTT at first visit, WBC, RBC, HGB, PLT, NEUT, APTT, IBIL, FFA, Crea, and urea before radio-chemotherapy, which are significant in univariate analysis into multivariate regression analysis, were taken. It turned out that RBC (OR = 10.060, 95% CI 2.679-37.777, p = 0.001), PLT (OR = 1.020, 95% CI 1.006-1.034, p = 0.005), and IBIL (OR = 0.710, 95% CI 0.561-0.898, p = 0.004) are independent predictors of severe TP in NPC. ROC analysis showed that the AUC of RBC, IBIL, PLT, and AGE is 0.746 (p < 0.001), 0.735 (p < 0.001), 0.702 (p = 0.001), and 0.734 (p < 0.001). New variables called joint predictors were calculated by a regression equation (Y = 2.309 * RBC - 0.343 * IBIL + 0.02 * PLT - 10.007), the AUC of which is 0.8700 (p < 0.001); best truncation value is >5.87 mmol/l. CONCLUSIONS: Lower RBC, PLT, and higher IBIL before concurrent radio-chemotherapy are independent risk factors causing severe TP during concurrent radio-chemotherapy of NPC. The RBC, PLT, and IBIL before concurrent radio-chemotherapy and joint predictor have a good predictive value to evaluate the risk of severe TP during concurrent radio-chemotherapy of NPC.

Juncus effusus fiber-based cellulose cigarette filter with 3D hierarchically porous structure for removal of PAHs from mainstream smoke.

Polycyclic aromatic hydrocarbons (PAHs) from cigarettes are one of the main pollutants affecting public health. Herein, a cellulose cigarette filter with three-dimensional (3D) hierarchically porous structure was fabricated using a natural cellulose Juncus effusus (JE) fiber, whose pore size was well controlled by biocompatible polyvinylpyrrolidone (PVP) using a simple dip-dry method. The adsorption capacity and mechanism of the PVP-JE filter tips (PJF) against PAHs were investigated in detail. Compared with conventional cellulose acetate filter tips (CAF), the cellulose PJF were superior at filtering and adsorbing of PAHs from mainstream smoke with the removal efficiency of 61.79 %, which was 22.57 % higher than that of CAF (39.22 %). The ternary structures including polymer filter membrane, 3D network, and interconnected channels were demonstrated as the main roles for highly effective removal of PAHs. The JE-based cellulose cigarette filter can be a promising candidature to broaden the application range of polysaccharide in pollutant elimination.