Advances in tumor immune microenvironment of head and neck squamous cell carcinoma: A review of literature.

Squamous cell carcinoma is seen as principal malignancy of head and neck. Tumor immune microenvironment plays a vital role in the occurrence, development and treatment of head and neck squamous cell carcinoma (HNSCC). The effect of immunotherapy, in particular, is closely related to tumor immune microenvironment. This review searched for high-quality literature included within PubMed, Web of Science, and Scopus using the keywords "head and neck cancers," "tumor microenvironment" and "immunotherapy," with the view to summarizing the characteristics of HNSCC immune microenvironment and how various subsets of immune cells promote tumorigenesis. At the same time, based on the favorable prospects of immunotherapy having been shown currently, the study is committed to pinpointing the latest progress of HNSCC immunotherapy, which is of great significance in not only further guiding the diagnosis and treatment of HNSCC, but also conducting its prognostic judgement.

Fibrinogen B ß promoter polymorphism may not be associated with pulmonary embolism.

OBJECTIVE: A prospective experiment was designed to explore all possible SNPs in the promoter region of fibrinogen B ß (FGB) and reveal the influence of these SNPs on susceptibility of pulmonary embolism. METHODS: In this 2-year randomized prospective study, we had totally recruited 203 volunteers. 58 PE patients (58 out of 145 VTE patients) and 114 healthy people were taken as case and control objects, respectively. FGB promoter was detected by gene sequencing. RESULTS: There were 6 SNPs in FGB promoter, which were ß-1420G/A, ß-993C/T, ß-854G/A, ß-455G/A, ß-249C/T, and ß-148C/T. Genotype frequencies of individual SNPs between the cases and controls were not statistically significant, all p > .05. After excluding subjects of COVID-19 infection within 6 months, the statistical results (35 PE patients vs 66 healthy people) were consistent. CONCLUSION: The susceptibility to pulmonary embolism may not be affected by any SNP in the FGB promoter region.

The overexpression and clinical significance of TBX15 in human gliomas.

T-box transcription factor 15 (TBX15) is upregulated in a variety of tumors and has been reported to promote uncontrolled proliferation of tumor cells and induce tumor cells to avoid apoptosis, thus accelerating the malignant transformation of malignant tumors. However, the prognostic value of TBX15 in glioma and its relationship with immune infiltration remain unknown. In this study, we intended to explore the prognostic value of TBX15 and its link to glioma immune infiltration and examine TBX15 expression in pan-cancer using RNAseq data in TPM format from TCGA and GTEx. TBX15 mRNA and protein expressions in glioma cells and adjacent normal tissue were detected and compared by RT-qPCR and Western blot. The effect of TBX15 on survival was assessed by Kaplan-Meier Method. The correlation between TBX15 upregulation and the clinicopathological characteristics of glioma patients was assessed by using TCGA databases, and the relationship between TBX15 and other genes in glioma was evaluated by using TCGA data. The top 300 genes most significantly associated with TBX15 were selected to establish a PPI network through the STRING database. The relationship between TBX15 mRNA expression and immune cell infiltration was explored by using ssGSEA and the TIMER Database. It was found that TBX15 mRNA expression in glioma tissues was significantly higher than that in the adjacent normal tissues, and this difference was most obvious in high-grade gliomas. TBX15 expression was increased in human gliomas and associated with worse clinicopathological characteristics and poorer survival prognosis in glioma patients. In addition, elevated TBX15 expression was linked to a collection of genes involved in immunosuppression. In conclusion, TBX15 played an important role in immune cell infiltration in glioma and may prove to be a predictor of the prognosis in glioma patients.

Carcinoma with signet ring cell differentiation associated with invasive breast cancer: A case report.

Carcinoma with signet ring cell differentiation is uncommon in patients with invasive breast cancer. Clinical evidence has suggested that the prognosis of this tumor is usually poor if the stage is advanced. The case of a 40-year-old female patient with primary cancer in the right breast accompanied by bilateral neck, axillary, right subclavian and mediastinal lymph node metastases, and left breast metastasis is presented in the current study. The patient developed superior vena cava syndrome and was restricted in lifting the upper right limb when presenting at the Third Affiliated Hospital of Shenzhen University, Shenzhen. The histopathological and immunohistochemical features included ~80% of the tumor cell area having a signet ring cell pattern, exhibiting the phenotype of lobular carcinoma, and ~20% of the tumor cell area exhibiting a ductal carcinoma immunophenotype with neuroendocrine expression The patient received chemotherapy with paclitaxel liposomes and doxorubicin hydrochloride liposomes according to the general guidelines for the treatment of stage IV breast carcinoma. The patient achieved a partial response after 4 cycles of treatment, and then experienced progressive disease in the form of brain metastasis after 6 cycles. Owing to the rarity of carcinoma with signet ring cell differentiation in invasive breast carcinoma, this case report discusses the patient's clinical and histopathological characteristics, and the treatment prognosis.

The Investigation of the Molecular Mechanism of Morinda officinalis How in the Treatment of Heart Failure.

Heart failure (HF) is a cardiovascular disease with an extremely high mortality rate. However, Morinda officinalis How (MO) has not been studied for cardiovascular purposes at this time, the aim of this study was to find new mechanism for the MO of treatment of HF through a bioinformatics and experimental validation. The present study also aimed to establish a link between the basic and clinical applications of this medicinal herb. MO compounds and targets were obtained by traditional Chinese medicine systems pharmacology (TCMSP) and Pubchem. Subsequently, HF targets were acquired from DisGeNET and the interactions of all the targets and other human proteins were obtained via String so as to establish a component-target interaction network by Cytoscape 3.7.2. All the targets of clusters were inserted into Database for Annotation, Visualization and Integrated Discovery (DAVID) to perform GO (gene ontology) enrichment analysis. Molecular docking was adopted to predict the targets of MO relevant to the treatment of HF and to further explore the associated pharmacological mechanisms. Subsequently, a series of in vitro experiments, including histopathological staining, immunohistochemical and immunofluorescence analyses were conducted for further verification. Moreover, western blot analysis and in vivo experiments were performed. The results indicated that MO alleviated apoptosis, regulated cholesterol metabolism and transport function, and reduced inflammation, which resulted in the successful treatment of HF. Beta-sitosterol, Asperuloside tetraacetate and americanin A were the key bioactive components of MO. ALB, AKT1, INS, STAT3, IL-6, TNF, CCND1, CTNNB1, CAT, and TP53 were the core potential targets, which were significantly associated with multiple pathways, namely the FoxO signaling pathway, the AMPK signaling pathway, and the HIF-1 signaling pathway. In vivo experiments validated that MO may protect against heart failure or treat this disease by increasing the levels of autophagy via the FoxO3 signaling pathway in rats. The present study suggested that a combination of network pharmacology prediction with experimental validation may offer a useful tool to characterize the molecular mechanism of action of the traditional Chinese medicine (TCM) MO in the treatment of HF.

Integrating Network Pharmacology and Bioinformatics to Explore the Effects of Dangshen (Codonopsis pilosula) Against Hepatocellular Carcinoma: Validation Based on the Active Compound Luteolin.

Purpose: This study aimed to explore the pharmacological mechanism of Dangshen (Codonopsis pilosula) against hepatocellular carcinoma (HCC) based on network pharmacology and bioinformatics, and to verify the anticancer effect of luteolin, the active ingredient of Codonopsis pilosula, on HCC cells. Methods: The effective compounds and potential targets of Codonopsis pilosula were established using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database. The genes related to HCC were obtained through the GeneCards database. The interactive genes were imported into the Visualization and Integrated Discovery database for Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) signal enrichment, and the hub genes were screened out. The Cancer Genome Atlas database was used to construct a prognosis model, and the prognosis and clinicopathological correlation were analyzed. In in vitro experiments, we verified the effects of luteolin, an active compound of Codonopsis pilosula, on the proliferation, cell cycle, apoptosis and migration of HCC cells. Results: A total of 21 effective compounds of Codonopsis pilosula and 98 potential downstream target genes were screened through the TCMSP database, and 1406 HCC target genes were obtained through the GeneCards database. Finally, 53 interacting genes between the two databases were obtained, among which, the 10 key node genes were CASP3, TP53, MDM2, AKT1, ESR1, BCL2L1, MCL1, HSP90AA1, CASP9, and CCND1, involving 77 typical GO terms and 72 KEGG signals. The Kaplan-Meier survival curve of the model group showed that the overall survival of the low-risk group was significantly higher than that of the high-risk group. Luteolin significantly inhibited the proliferation and migration of HCC cells, induced apoptosis, and increased the G2/M phase ratio. Mechanistically, luteolin significantly inhibited the phosphorylation of MAPK-JNK and Akt (Thr308) and subsequently led to upregulation of ESR1. Pharmacological inhibition of ESR1 with fulvestrant enhanced cell viability and migration and attenuated apoptosis. Conclusion: Codonopsis pilosula has potential for clinical development due to its anti-HCC properties. Luteolin, the effective component of Codonopsis pilosula, plays anti-HCC role through AKT- or MAPK-JNK signaling mediated ESR1.

Network Pharmacology Was Used to Predict the Active Components and Prospective Targets of Paeoniae Radix Alba for Treatment in Endometriosis.

Endometriosis is one of the most common benign gynecologic diseases. Paeoniae Radix Alba (PRA) has been utilized to treat endometriosis. We wished to identify potential targets for PRA in the treatment of endometriosis, as well as to provide a groundwork for future studies into its pharmacological mechanism of action. Network pharmacology was employed to conduct investigations on PRA. Target proteins were chosen from the components of PRA for endometriosis treatment. A protein-protein interaction (PPI) was established using overlapping genes. Analyses of enrichment of function and signaling pathways were undertaken using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes databases to select "hub genes." Finally, the feasibility of analysis based on network pharmacology was determined using real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. We demonstrated that PRA has 25 bioactive components and 167 putative targets that are therapeutically important. The anti-inflammatory and immune-boosting actions of tumor necrosis factor, albumin, signal transducer and activator of transcription (STAT)3, mitogen-activated protein kinase, Jun, interleukin (IL)-1B, prostaglandin-endoperoxide synthase 2, matrix metalloproteinase-9, vascular endothelial growth factor A, and IL-6 were identified as prospective targets. Seven major compounds in PRA and related to the STAT3 pathway could bind spontaneously to it. RT-qPCR and western blotting showed that expression of STAT3 and phospho-STAT3 was reduced significantly after PRA intervention. Hence, analyses of the active components of traditional Chinese medicine formulations through network pharmacology may open up new ideas for the treatment of diseases.

Role of ferroptosis-related genes in coronary atherosclerosis and identification of key genes: integration of bioinformatics analysis and experimental validation.

BACKGROUND: Coronary atherosclerosis (CA) is the most common type of atherosclerosis. However, the inherent pathogenesis and mechanisms of CA are unclear, and the relationship with ferroptosis-related genes (FRGs) has not been reported. The purpose of this study was to use bioinformatics techniques to evaluate potential therapeutic targets for CA.Please provide the given name for author "Dingshun".Please provide the given name for author "Dingshun". METHODS: First, the GSE132651 dataset was acquired from the Gene Expression Omnibus database. Gene Ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, and Protein-Protein interaction network were successively conducted. Next, overlapping genes between hub genes and CA genes were found. FRGs were found when comparing the CA group with the normal group. The correlation between overlapping genes and FRGs was further analyzed. At last, we performed Elisa to validate the expression of these genes in human blood specimens. Mice aortic tissues were used for western blot to detect the expression of proteins. RESULTS: Based on the GSE132651 dataset, 102 differentially expressed genes were identified. Five overlapping genes between hub genes and CA genes were found (CCNA2, RRM2, PBK, PCNA, CDK1). TFRC and GPX4 were found to be FRGs. TFRC was positively correlated with CCNA2, PBK, PCNA, CDK1, RRM2, with CDK1 being the strongest correlation. GPX4 was negatively correlated with these genes, among which CCNA2 was the strongest correlation. The ELISA results showed that CCNA2, CDK1, and TFRC expression were markedly increased in serum of the CA samples compared with controls, while GPX4 expression was markedly decreased in the CA samples. The western blot results show that GPX4 expression was lower in the model group, TFRC, CDK1, and CCNA2 protein expression were high in the model group. CONCLUSIONS: Ferroptosis-related genes GPX4 and TFRC were closely correlated with the identified overlapping genes CCNA2 and CDK1, which may serve as targeted therapies for the treatment of CA.

miRNA-Mediated Low Expression of EPHX3 Is Associated with Poor Prognosis and Tumor Immune Infiltration in Head and Neck Squamous Cell Carcinomas.

The aim of this study was to explore the regulatory role of epoxide hydrolase 3 (EPHX3) in head and neck squamous cell carcinoma (HNSCC) and to analyze its bioinformatic function, as well as, to screen and predict the miRNAs that can regulate EPHX3 expression in HNSCC. We examined the expression profile and prognostic potential of EPHX3 in TCGA and GTEX databases and performed functional enrichment analysis of EPHX3 using string database. Subsequently, we analyzed the regulatory role of miRNAs on EPHX3, including expression analysis, correlation analysis, and survival analysis. In addition, we also used TIMER to investigate the relationship among EPHX3 expression level, immune checkpoints, and immune infiltration in HNSCC. The results of data analysis after TGCA showed that EPHX3 is a key regulator of tumorigenesis in 13 cancers and can be used as a marker of poor prognosis in HNSCC patients. Bioinformatics analysis revealed that miR-4713-3p is a key miRNA of EPHX3 in HNSCC. Together, our findings indicate that EPHX3 exerts its anticancer effects by suppressing tumor immune checkpoint expression and immune cell infiltration. Overall, our data uncovered miRNA-mediated EPHX3 downregulation as a contributor to poor HNSCC prognosis and reduced tumor immune infiltration.

Prediction of the Active Components and Possible Targets of Xanthii Fructus Based on Network Pharmacology for Use in Chronic Rhinosinusitis.

Chronic rhinosinusitis (CRS) is a complex condition brought on for many reasons, and its prevalence is rising gradually around the world. Xanthii Fructus (XF) has been used in the treatment of CRS for decades and is effective. The chemical and pharmacological profiles of XF, on the other hand, are still unknown and need to be clarified. The potential mechanisms of XF in CRS treatment were investigated using a network pharmacology approach in this study. OB and DL were in charge of screening the bioactive components in XF and drug-likeness. TCMSP and PubChem databases were used to identify prospective XF proteins, whereas GeneCards and the DisGeNET database were used to identify potential CRS genes. An interactive network of XF and CRS is built using the STRING database based on common goals identified by the online tool Venny. Cytoscape was used to visualize the topological characteristics of nodes, while the biological function pathways were identified by GO Knowledge Base, KEGG. There were 26 bioactive components and 115 potential targets in XF that bind to CRS or are considered therapeutically relevant. Five significant signaling pathways have been found for CRS by the pathway analysis including the HIF-1 signaling pathway, TNF signaling pathway, Toll-like receptor signaling pathway, NOD-like receptor signaling pathway, and PI3K-Akt signaling pathway. We simultaneously confirmed that the PI3K-Akt pathway promotes the development of CRS. Finally, this study took a holistic approach to the pharmacological actions and molecular mechanisms of XF in the treatment of CRS. TNF, INS, CCL2, CXCL8, IL-10, VEGFA, and IL-6 have all been identified as potential targets for anti-inflammatory and immune-boosting effects. This network pharmacology prediction could be useful in manifesting the molecular mechanisms of the Chinese herbal compound XF for CRS.

[Disinfection By-products in Drinking Water and Their Control Strategies: A Review].

Disinfection by-products(DBPs) are secondary pollutants generated by the reaction of disinfectants with organic or inorganic precursors during drinking water disinfection. DBPs have received considerable global attention due to their carcinogenic, teratogenic, and mutagenic characteristics. Focusing on drinking water, this paper introduces the main classification and research history of DBPs, and then summarizes the concentration levels of common DBPs in drinking water, and DBPs regulatory compliance in global drinking water standards. Further, the control strategies for DBPs in drinking water, including source control, process control, DBPs removal and integrated control are introduced together with the advantages and disadvantages. Finally, a summary and review of the current level and future trends of DBPs research in China are presented with the proposed control strategies. On the one hand, when evaluating the control effect of a process or technology, the DBPs concentration and comprehensive toxicity should be considered; on the other hand, in order to realize the efficient control of DBPs in drinking water, the focus should be on the integrated methods coupling different DBPs control methods.

A Pan-Cancer Analysis of Cystatin E/M Reveals Its Dual Functional Effects and Positive Regulation of Epithelial Cell in Human Tumors.

Cystatin E/M (CST6), a representative cysteine protease inhibitor, plays both tumor-promoting and tumor-suppressing functions and is pursued as an epigenetically therapeutic target in special cancer types. However, a comprehensive and systematic analysis for CST6 in pan-cancer level is still lacking. In the present study, we explored the expression pattern of CST6 in multiple cancer types across ∼10,000 samples from TCGA (The Cancer Genome Atlas) and ∼8,000 samples from MMDs (Merged Microarray-acquired Datasets). We found that the dynamic expression alteration of CST6 was consistent with dual function in different types of cancer. In addition, we observed that the expression of CST6 was globally regulated by the DNA methylation in its promoter region. CST6 expression was positively correlated with the epithelial cell infiltration involved in epithelial-to-mesenchymal transition (EMT) and proliferation. The relationship between CST6 and tumor microenvironment was also explored. In particular, we found that CST6 serves a protective function in the process of melanoma metastasis. Finally, the clinical association analysis further revealed the dual function of CST6 in cancer, and a combination of the epithelial cell infiltration and CST6 expression could predict the prognosis for SKCM patients. In summary, this first CST6 pan-cancer study improves the understanding of the dual functional effects on CST6 in different types of human cancer.

Financial Literacy, Health Engagement, and Residents' Health: Evidence from China.

This study took residents' health level as the research object, adopted the perspective of financial literacy, and used the 2014-2018 China Family Panel Studies data to analyze the impact of financial literacy on the residents' health. The study found that financial literacy could have a significant positive impact on the residents' health, with long-term effects. Furthermore, it promoted the residents' health engagement and improved their health through the intermediary effects of income and health expenditure. In addition, the impact of financial literacy on the residents' health was heterogeneous between urban and rural areas. Compared with the case for rural residents, the improvement of financial literacy significantly improved the health of the urban residents. The outcomes of this research were the exploration of means to improve residents' health from a new economic perspective, promote residents' health engagement, and improve residents' health.

Frost Damage in Tight Sandstone: Experimental Evaluation and Interpretation of Damage Mechanisms.

Low-porosity tight rocks are widely used as building and engineering materials. The freeze-thaw cycle is a common weathering effect that damages building materials in cold climates. Tight rocks are generally supposed to be highly frost-resistant; thus, studies on frost damage in tight sandstone are rare. In this study, we investigated the deterioration in mechanical properties and changes in P-wave velocity with freeze-thaw cycles in a tight sandstone. We also studied changes to its pore structure using nuclear magnetic resonance (NMR) technology. The results demonstrate that, with increasing freeze-thaw cycles, (1) the mechanical strength (uniaxial compressive, tensile, shear strengths) exhibits a similar decreasing trend, while (2) the P-wave velocity and total pore volume do not obviously increase or decrease. (3) Nanopores account for >70% of the pores in tight sandstone but do not change greatly with freeze-thaw cycles; however, the micropore volume has a continuously increasing trend that corresponds to the decay in mechanical properties. We calculated the pressure-dependent freezing points in pores of different diameters, finding that water in nanopores (diameter <5.9 nm) remains unfrozen at -20 °C, and micropores >5.9 nm control the evolution of frost damage in tight sandstone. We suggest that pore ice grows from larger pores into smaller ones, generating excess pressure that causes frost damage in micropores and then nanopores, which is manifested in the decrease in mechanical properties.

Wireless bioreactor for anaerobic cultivation of bacteria.

Anaerobic cultivation methods of bacteria are indispensable in microbiology. One methodology is to cultivate the microbes in anaerobic enclosure with oxygen-adosrbing chemicals. Here, we report an electronic extension of such strategy for facultative anaerobic bacteria. The technique is based a bioreactor with entire operation including turbidity measurement, fluidic mixing, and gas delivery in an anaerobic enclosure. Wireless data transmission is employed and the anaerobic condition is achieved with gas pack. Although the technique is not meant to completely replace the anaerobic chamber for strict anaerobic bacteria, it provides a convenient way to bypass the cumbersome operation in anaerobic chamber for facultative anaerobic bacteria. Such a cultivation strategy is demonstrated with Escherichia coli with different carbon sources and hydrogen as energy source.

Successful Lower Limb Replantation of Knee-Level Amputation in a Child: A Case Report.

Replantation of a lower extremity amputated at the knee joint level in a child is rare. We present a case of a 3-year-old child with his right leg totally severed from the knee joint in a traumatic accident. After 5 hours of cold ischemia time, together with antishock therapies, the child underwent leg replantation under stable conditions. The replanted lower limb finally survived after several surgical procedures. The patient was discharged 4 weeks after admission and had restored partial motor and sensory functions 6 months after surgery. During follow-ups, the patient underwent sustained rehabilitation and recovered well. Two years after replantation, secondary knee reconstruction was performed and yielded favorable aesthetic and functional improvement. In brief, a successful knee-level replantation in a child is attributed to correct preoperative first aid, excellent microsurgical skills, and intensive postoperative management.

The composition and variation of the BCR CDR3s in gastric cancer.

Gastric cancer (GC) is the fourth most common type of cancer and the second most common cause of cancer-associated mortality worldwide. B cell-associated autoantibodies against tumor-associated antigens are attractive biomarkers for the development of noninvasive serological tests for the early detection of cancer. This is due to their specificity and stability in the sera. In the present study multiplex polymerase chain reaction and Illumina high-throughput sequencing (HTS) was used to study the composition and variation of the B cell receptor (BCR) complimentary-determining region 3 (CDR3) in GC. The peripheral blood, cancer tissues and peri-cancer tissues were included from 7 patients with GC. On average there was a total of 403,959 CDR3 sequences, with 72,367 unique CDR3 nt sequences and 61,709 unique CDR3 aa sequences per sample identified, which are critical for further understanding the BCR repertoire in GC. The details of GC CDR3s may accelerate the screening process for possible new autoantigens and may provide additional information necessary for generating effective B cell targeted diagnosis and therapeutic strategies.

Electrochemical determination of sulfide in fruits using alizarin-reduced graphene oxide nanosheets modified electrode.

This study presents a new approach for rapid detection of sulfide using a glassy carbon electrode (GCE) modified with alizarin (Az) and reduced graphene oxide (rGO) nanosheets. The fabricate Az-rGO/GCE sensor shows a notable electrocatalytic activity to sulfide oxidation. The currents of anodic peak centered at +465mV in 0.2M pH 7.0 phosphate buffer were related linearly to the concentrations of sulfide, based on the cyclic voltammetric studies. The linear range was 0.002-3.28mM, and the detection limit was 1µM. The proposed method was applied in sulfide determination of hydrogen sulfide pretreated fruits, and the method was also verified with recovery studies.

Identification and quantification analysis of nonlinear dynamics properties of combustion instability in a diesel engine.

The cycling combustion instabilities in a diesel engine have been analyzed based on chaos theory. The objective was to investigate the dynamical characteristics of combustion in diesel engine. In this study, experiments were performed under the entire operating range of a diesel engine (the engine speed was changed from 600 to 1400 rpm and the engine load rate was from 0% to 100%), and acquired real-time series of in-cylinder combustion pressure using a piezoelectric transducer installed on the cylinder head. Several methods were applied to identify and quantitatively analyze the combustion process complexity in the diesel engine including delay-coordinate embedding, recurrence plot (RP), Recurrence Quantification Analysis, correlation dimension (CD), and the largest Lyapunov exponent (LLE) estimation. The results show that the combustion process exhibits some determinism. If LLE is positive, then the combustion system has a fractal dimension and CD is no more than 1.6 and within the diesel engine operating range. We have concluded that the combustion system of diesel engine is a low-dimensional chaotic system and the maximum values of CD and LLE occur at the lowest engine speed and load. This means that combustion system is more complex and sensitive to initial conditions and that poor combustion quality leads to the decrease of fuel economy and the increase of exhaust emissions.