Prognostic, immunity, stemness, and anticancer drug sensitivity characterization of pyroptosis related genes in non-small cell lung cancer.

BACKGROUND: Pyroptosis plays a pivotal role in the tumor immune microenvironment (TME) dynamics, particularly in non-small cell lung cancer (NSCLC). The aim of our study was to explore its effects on tumor progression, TME patterns, and the efficacy of therapeutic interventions in NSCLC. METHODS: Our investigation encompassed a thorough analysis of pyroptosis-related genes (PRGs), integrating immunohistochemistry (IHC) data, TME characteristics, stemness indices, and anticancer drug sensitivities. We aimed to analyze mRNA expression profiles across various cancers, constructing benchmark datasets to assess the clinical significance of PRGs in NSCLC. This included evaluating their association with clinical responses and efficacy. Notably, both our and HPA IHC data demonstrated significantly elevated GSDMD-N protein levels in lung squamous cell carcinoma (LUSC) tissues. RESULTS: The expression of PRGs differed significantly between tumor and normal tissues across various cancers, as validated by IHC data, and was correlated with prognosis (p < 0.05). Moreover, our investigation revealed significant differences (p < 0.05) in the expression of the PRGs among distinct TME subtypes categorized as C1 (wound healing), C3 (inflammatory), C2 (IFN-gamma dominant), C5 (immunological quiet), C4 (lymphocyte deficient), and C6 (TGF-beta dominant). Additionally, our research on anticancer drug sensitivity uncovered compelling connections between specific anticancer medications and the expression of PRGs, including GSDMD, ELANE, IL18, and CHMP4A (p < 0.05). CONCLUSION: Our study provided valuable insights into the critical role of PRGs in TME modulation, tumor stemness, and anticancer drug sensitivity across diverse cancers. Our findings illuminate the intricate relationship between pyroptosis and the TME, offering new perspectives for enhancing NSCLC treatment and prognosis.

Chinese expert consensus on interventional diagnosis and management of acquired digestive-respiratory tract fistulas (second edition).

Acquired digestive-respiratory tract fistulas occur with abnormal communication between the respiratory tract and digestive tract caused by a variety of benign or malignant diseases, leading to the alimentary canal contents in the respiratory tract. Although various departments have been actively exploring advanced fistula closure techniques, including surgical methods and multimodal therapy, some of which have gotten good clinical effects, there are few large-scale evidence-based medical data to guide clinical diagnosis and treatment. The guidelines update the etiology, classification, pathogenesis, diagnosis, and management of acquired digestive-respiratory tract fistulas. It has been proved that the implantation of the respiratory and digestive stent is the most important and best treatment for acquired digestive-respiratory tract fistulas. The guidelines conduct an in-depth review of the current evidence and introduce in detail the selection of stents, implantation methods, postoperative management and efficacy evaluation.

Bacterial biomarkers capable of identifying recurrence or metastasis carry disease severity information for lung cancer.

Background: Local recurrence and distant metastasis are the main causes of death in patients with lung cancer. Multiple studies have described the recurrence or metastasis of lung cancer at the genetic level. However, association between the microbiome of lung cancer tissue and recurrence or metastasis remains to be discovered. Here, we aimed to identify the bacterial biomarkers capable of distinguishing patients with lung cancer from recurrence or metastasis, and how it related to the severity of patients with lung cancer. Methods: We applied microbiome pipeline to bacterial communities of 134 non-recurrence and non-metastasis (non-RM) and 174 recurrence or metastasis (RM) samples downloaded from The Cancer Genome Atlas (TCGA). Co-occurrence network was built to explore the bacterial interactions in lung cancer tissue of RM and non-RM. Finally, the Kaplan-Meier survival analysis was used to evaluate the association between bacterial biomarkers and patient survival. Results: Compared with non-RM, the bacterial community of RM had lower richness and higher Bray-Curtis dissimilarity index. Interestingly, the co-occurrence network of non-RM was more complex than RM. The top 500 genera in relative abundance obtained an area under the curve (AUC) of 0.72 when discriminating between RM and non-RM. There were significant differences in the relative abundances of Acidovorax, Clostridioides, Succinimonas, and Shewanella, and so on between RM and non-RM. These biomarkers played a role in predicting the survival of lung cancer patients and were significantly associated with lung cancer stage. Conclusion: This study provides the first evidence for the prediction of lung cancer recurrence or metastasis by bacteria in lung cancer tissue. Our results highlights that bacterial biomarkers that distinguish RM and non-RM are also associated with patient survival and disease severity.

Potential active constituents responsible for treating acute pharyngitis in the flowers of Hosta plantaginea (Lam.) Aschers and their pharmacokinetics.

In Asia, the flower of Hosta plantaginea (Lam.) Aschers (hosta flower) is both an edible food and medicine. The hosta flower is often used as a material for cooking porridge and scented tea and in combination with other plants for alleviating pharyngitis. To clarify the anti-pharyngitis effect of the hosta flower and evaluate its potential active ingredients, an ethanol extract of the hosta flower was prepared and partially purified via chromatography on a column packed with D101 macroporous resin, which was eluted with different concentrations of ethanol. The anti-pharyngitis effect of the crude extract and the various partially purified fractions was examined in an ammonia-induced acute pharyngitis rat model. The 30% ethanol-eluted fraction significantly alleviated the severity of pharyngitis in the rat, as evaluated by changes in the levels of cytokines (IL-1ß, IL-6, and TNF-α) and histological changes in the pharynx tissues. Subsequent HPLC-QTOF/MS (high-performance liquid chromatography coupled with quadrupole-time of flight tandem mass spectrometry) analysis of this fraction revealed kaempferol and its glycosides as the main components. Three of the main components were isolated and identified by 1D NMR. Their pharmacokinetics were studied for the first time by UHPLC-QQQ/MS (ultrahigh-performance liquid chromatography coupled with mass spectrometry). The findings suggested that the 30% ethanol-eluted fraction of the hosta flower extract may be a potential functional food for treating pharyngitis.

Agent Repurposing for the Treatment of Advanced Stage Diffuse Large B-Cell Lymphoma Based on Gene Expression and Network Perturbation Analysis.

Over 50% of diffuse large B-cell lymphoma (DLBCL) patients are diagnosed at an advanced stage. Although there are a few therapeutic strategies for DLBCL, most of them are more effective in limited-stage cancer patients. The prognosis of patients with advanced-stage DLBCL is usually poor with frequent recurrence and metastasis. In this study, we aimed to identify gene expression and network differences between limited- and advanced-stage DLBCL patients, with the goal of identifying potential agents that could be used to relieve the severity of DLBCL. Specifically, RNA sequencing data of DLBCL patients at different clinical stages were collected from the cancer genome atlas (TCGA). Differentially expressed genes were identified using DESeq2, and then, weighted gene correlation network analysis (WGCNA) and differential module analysis were performed to find variations between different stages. In addition, important genes were extracted by key driver analysis, and potential agents for DLBCL were identified according to gene-expression perturbations and the Crowd Extracted Expression of Differential Signatures (CREEDS) drug signature database. As a result, 20 up-regulated and 73 down-regulated genes were identified and 79 gene co-expression modules were found using WGCNA, among which, the thistle1 module was highly related to the clinical stage of DLBCL. KEGG pathway and GO enrichment analyses of genes in the thistle1 module indicated that DLBCL progression was mainly related to the NOD-like receptor signaling pathway, neutrophil activation, secretory granule membrane, and carboxylic acid binding. A total of 47 key drivers were identified through key driver analysis with 11 up-regulated key driver genes and 36 down-regulated key diver genes in advanced-stage DLBCL patients. Five genes (MMP1, RAB6C, ACCSL, RGS21 and MOCOS) appeared as hub genes, being closely related to the occurrence and development of DLBCL. Finally, both differentially expressed genes and key driver genes were subjected to CREEDS analysis, and 10 potential agents were predicted to have the potential for application in advanced-stage DLBCL patients. In conclusion, we propose a novel pipeline to utilize perturbed gene-expression signatures during DLBCL progression for identifying agents, and we successfully utilized this approach to generate a list of promising compounds.

Prognostic factors and survival outcome of primary pulmonary acinar cell carcinoma.

PURPOSE: The objective of our study was to investigate the epidemiologic characteristics and prognostic factors in patients with pulmonary acinar cell carcinoma (PACC). METHODS: PACC patients diagnosed between 1975 and 2016 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The trend in PACC incidence was assessed using joinpoint regression software. Overall survival (OS) and disease-specific survival (DSS) were evaluated using the Kaplan-Meier method and log-rank test. Univariate and multivariate Cox regression analysis was performed to identify the independent prognostic factors for OS and DSS. Nomograms to predict survival possibilities were constructed based on the identified independent prognostic factors. RESULTS: A total of 2918 patients were identified with PACC. The mean age was 65.2 ± 8.95 years with a female to male of 1.6:1. The incidence of PACC steadily increased by an annual percentage change (APC) of 3.2% (95% CI 2.1-4.4, p < 0.05). Multivariate Cox regression analysis revealed that age, gender, race, stage, grade, tumor size, number of positive lymph nodes, surgery, and chemotherapy were independent prognostic factors for survival. Nomograms specifically for PACC were constructed to predict 1- and 5-year OS and DSS possibility, respectively. The concordance index (C-index) and calibration plots showed the established nomograms had robust and accurate performance. CONCLUSION: PACC was rare but the incidence has been steadily increasing over the past four decades. Survival has improved in recent years. Surgery or chemotherapy could provide better OS and DSS. The established nomograms specifically for PACC were robust and accurate in predicting 1- and 5-year OS and DSS.

Screening and tissue distribution of protein tyrosine phosphatase 1B inhibitors in mice following oral administration of Garcinia mangostana L. ethanolic extract.

Garcinia mangostana L. (mangosteen) is a tropical fruit that is rich in xanthones and is thought to have an anti-diabetic effect. In this study, we screened for the xanthones in mangosteen that could inhibit the activity of protein tyrosine phosphatase 1B (PTP1B), an enzyme that is targeted by diabetic drugs. Mice were orally administered mangosteen extract and blood samples were screened for the presence of PTP1B-interacting xanthones. Six such compounds (1-6) were identified by UF-HPLC-QTOF-MS and their inhibition against PTP1B was confirmed by activity assay. Among them, garcinone E (5) was found to be the most effective PTP1B inhibitor (IC50 = 0.43 µM). Tissue distribution analysis showed that the six compounds were distributed in eleven tissues, including the liver, muscle, fat, stomach, large intestine, small intestine, brain, kidney, heart, lung, and spleen. The results demonstrated that mangosteen might be a promising source of natural compounds with high PTP1B-inhibitory activity.

Bronchial arterial embolization may reduce the risk of severe bleeding in central airway obstruction due to renal cell carcinomas during bronchoscopic procedures.

BACKGROUND: Hemorrhage is a life-threatening complication during bronchoscopic intervention in patients with central airway obstruction (CAO) due to metastatic renal cell carcinoma (RCC). Whether pre-bronchoscopic bronchial arterial embolization (BAE) can reduce the risk of severe bleeding in CAO patients due to metastatic RCC remains unclear. METHODS: A total of 31 CAO patients due to metastatic RCC were included retrospectively and divided into a BAE group (receiving pre-bronchoscopic BAE) and non-BAE group in this study. Based on computed tomography (CT) and bronchoscopic findings, tumor debulking was used to reconstruct the airway during interventional bronchoscopy. The primary outcome was the incidence of severe bleeding during bronchoscopic procedures. Bleeding-related complications, Karnofsky performance score (KPS) and dyspnea score were also analyzed over a 1-month observation period. RESULTS: There were no significant differences between the two groups in baseline characteristics, including patients' features, tumor morphology under CT scannings, tumor site, and obstruction degree under bronchoscopic examination. Procedure-related bleeding occurred in all 31 patients. Pre-bronchoscopic BAE significantly reduced the incidence of moderate and major bleeding when compared with that in the non-BAE group. The incidence of poor visualization and hypoxia was also reduced significantly in the BAE group. There was no significant difference in KPS and dyspnea score between the BAE and non-BAE groups at 1 month follow up. CONCLUSION: Pre-bronchoscopic BAE might be a feasible option to reduce the risk of severe bleeding for CAO patients due to metastatic RCC during bronchoscopic intervention. Interventional bronchoscopy was a safe and effective procedure for CAO due to metastatic RCC.The reviews of this paper are available via the supplemental material section.

High expression of PTBP1 promote invasion of colorectal cancer by alternative splicing of cortactin.

Polypyrimidine tract-binding protein 1 (PTBP1) involving in almost all steps of mRNA regulation including alternative splicing metabolism during tumorigenesis due to its RNA-binding activity. Initially, we found that high expressed PTBP1 and poor prognosis was interrelated in colorectal cancer (CRC) patients with stages II and III CRC, which widely different in prognosis and treatment, by immunohistochemistry. PTBP1 was also upregulated in colon cancer cell lines. In our study, knockdown of PTBP1 by siRNA transfection decreased cell proliferation and invasion in vitro. Denovirus shRNA knockdown of PTBP1 inhibited colorectal cancer growth in vivo. Furthermore, PTBP1 regulates alternative splicing of many target genes involving in tumorgenesis in colon cancer cells. We confirmed that the splicing of cortactin exon 11 which was only contained in cortactin isoform-a, as a PTBP1 target. Knockdown of PTBP1 decreased the expression of cortactin isoform-a by exclusion of exon 11. Also the mRNA levels of PTBP1 and cortactin isoform-a were cooperatively expressed in colorectal cancer tissues. Knocking down cortactin isoform-a significantly decreased cell migration and invasion in colorectal cancer cells. Overexpression of cortactin isoform-a could rescue PTBP1-knockdown effect of cell motility. In summary the study revealed that PTBP1 facilitates colorectal cancer migration and invasion activities by inclusion of cortactin exon 11.

Ab initio study of mechanism of forming a spiro-heterocyclic ring compound with Si and Ge between dimethylsilylene germylidene (Me(2)Si = Ge:) and acetone.

The mechanism of the cycloaddition reaction between singlet state dimethylsilylene germylidene (Me(2)Si = Ge:) and acetone has been investigated with CCSD(T)//B3LYP/6-31G* method. From the potential energy profile, it could be predicted that the reaction has one dominant reaction pathway. The reaction rules presented are that the two reactants first form a Si-heterocyclic four-membered ring germylene through the [2 + 2] cycloaddition reaction. Because of the 4p unoccupied orbital of Ge atom in the Si-heterocyclic four-membered ring germylene and the π orbital of acetone forming a π→p donor-acceptor bond, the Si-heterocyclic four-membered ring germylene further combines with acetone to form an intermediate. Because the Ge atom in the intermediate happens sp(3) hybridization after transition state, then, the intermediate isomerizes to a spiro-heterocyclic ring compound with Si and Ge via a transition state.