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Chemotherapy-induced peripheral neuropathy (CIPN) is among the most disabling and frustrating problems for cancer survivors. The neurotoxicity caused by cisplatin varies greatly among patients, and few predictors of appearance, duration of symptoms, susceptibility, or severity are available. A deeper understanding of the mechanisms underlying individual differences in status, severity, or sensitivity in response to cisplatin treatment is therefore required. By analyzing the GSE64174 gene expression profile and constructing a weighted gene co-expression network analysis (WGCNA) network, we screened gene modules and hub genes related to CIPN status, severity and sensitivity. We first identified the transcriptome profile of mouse dorsal root ganglion (DRG) samples and transformed their genes to human DRG counterparts. We then constructed WGCNA gene modules via optimal soft-threshold power-identification and module-preservation analysis. Comprehensive analysis and identification of module hub genes were performed via functional-enrichment analysis and significant common hub genes were identified, including "Cytoscape_cytoHubba," "Cytoscape_MCODE," and "Metascape_MCODE." Brown, green, and blue modules were selected to represent CIPN sensitivity, status, and severity, respectively, via trait-module correlational analysis. Additionally, functional enrichment analysis results indicated that these three modules were associated with some crucial biological functions, such as neutrophil migration, chemokine-mediated signaling pathway, and PI3K-Akt signaling pathway. We then identified seven common hub genes via three methods, including CXCL10, CCL21, CCR2, CXCR4, TLR4, NPY1R, and GALR2, related to CIPN status, severity and sensitivity. Our results provide possible targets and mechanism insights into the development and progress of CIPN, which can guide further transformation and pre-clinical research.

Retinoblastoma (RB) is the most common type of intraocular malignant tumor that occurs in childhood. AR-42, a member of a newly discovered class of phenylbutyrate-derived histone deacetylase inhibitors, exerts antitumor effects on many cancers. In the present study, we initially evaluated the effect of AR-42 towards RB cells and explored the underlying mechanism in this disease. Our results found that AR-42 showed powerful antitumor effects at low micromolar concentrations by inhibiting cell viability, blocking cell cycle, stimulating apoptosis in vitro, and suppressing RB growth in a mouse subcutaneous tumor xenograft model. Furthermore, the AKT/nuclear factor-kappa B signaling pathway was disrupted in Y79 cells treated with AR-42. In conclusion, we propose that AR-42 might be a promising drug treatment for RB.

A giant retrosternal goiter can lead to compression of vital organs in the mediastinum with high risk of acute cardiorespiratory decompensation. Additionally, patients with acromegaly are prone to developing severe airway obstruction and ventilation difficulties during anesthetic induction, leading to hypoxia and an increased partial pressure of carbon dioxide. Therefore, more comprehensive airway management strategies are needed. We herein describe a 57-year-old man with acromegaly and severe tracheal obstruction caused by a giant retrosternal goiter. He presented with a 1-week history of progressive dyspnea and was scheduled to undergo right lobe thyroidectomy and retrosternal goiter thyroidectomy. We created a comprehensive emergency plan for a difficult airway, including regional and topical anesthesia for awake endotracheal intubation, sevoflurane inhalation, small doses of midazolam and sufentanil to increase tolerance, self-made extended-length tracheostomy, video laryngoscope-assisted fiber-optic bronchoscopy, extracorporeal membrane oxygenation, and surgical tracheostomy. Importantly, tetracaine was inhaled through an atomizer, and a laryngotracheal topical anesthesia applicator was used to spray the larynx with 1% tetracaine to reduce stimulation during intubation. The giant goiter was successfully removed through the cervical approach. A carefully designed airway management strategy and close communication among a multidisciplinary operation team are the basis of perioperative anesthetic management for these patients.

BRAF inhibitors (BRAFi) that target BRAF V600E kinase, a driver mutation found in 50% of melanomas, show a significant antitumor response, but the common emergence of acquired resistance remains a challenge. Abnormal expression of RAF isoforms CRAF and ARAF reactivates pERK1/2, which plays crucial roles in the acquisition of resistance of melanoma cells. However, the mechanisms of dysregulation of RAF isoforms in resistant melanoma cells remain unknown. Here, we identified NONO interacted with and stabilized both CRAF and ARAF in melanoma cells, and that NONO was acetylated at 198K by p300 acetyltransferase, which stabilized NONO via antagonizing its ubiquitination/degradation mediated by RNF8. The upregulation of both p300 and NONO promoted the rebound of pERK1/2 and the subsequent resistance of melanoma cells to BRAFi, and the activation of ERK1/2 in turn induced p300 to form a positive feedback loop in resistant melanoma cells. There was a positive correlation between p300 and NONO in resistant melanoma cells and clinical samples, and p300 inhibitor C646 overcame the resistance of resistant melanoma cells to BRAF inhibitors in vitro and in vivo. Our findings reveal that targeting the positive feedback loop of p300-NONO-CRAF/ARAF-pERK1/2 may be excellent strategies to overcome the resistance of BRAF inhibitors for melanoma patients.

Aim: To develop an oxidative phosphorylation (OXPHOS)-related gene signature of lung adenocarcinoma (LUAD). Materials & methods: We split The Cancer Genome Atlas LUAD cohort into a training set and a test set; we used the least absolute shrinkage and selection operator Cox method to structure the OXPHOS-related prognostic signature in the training set and verified in the test set and GSE30219 dataset. Meanwhile, the diagnostic model was constructed using the logistic Cox method. Results: The signature consisted of seven genes ( LDHA, CFTR, HSPD1, SNHG3, MAP1LC3C, COX6B2, and TWIST1). LUAD patients were divided into high- and low-risk groups, demonstrating good diagnostic and prognostic capabilities. Conclusion: We developed the first-ever OXPHOS-related signature with both prognostic predictive power and diagnostic efficacy.

Aim: This study aimed to explore the genetic and epigenetic similarities between chronic obstructive pulmonary disease (COPD) and lung adenocarcinoma (LUAD). Materials & methods: We mainly used Weighted correlation network analysis, protein–protein interaction network and pivot analysis to identify hub modules, bridge regulators, bridge genes and hub-driving genes in both diseases and carried out verifying using external datasets. Results: We identified eight bridge regulators, 19 key molecules in the COPD model and ten key molecules in the LUAD model. Moreover, we validated that CDC5L could be a reliable biomarker in COPD and may regulate cell proliferation and metastasis in LUAD via promoter methylation. Conclusion: Our results might form a theoretical foundation for future study at an epigenetic level.

Recent mounting studies showed that neuroinflammation caused by surgery or anesthesia is closely related to postoperative cognitive dysfunction (POCD). This study investigated the effect of mineralocorticoid receptor (MR) on neuroinflammation and POCD. To detect the MR effect in an animal model, we randomly divided rats into control, anesthesia, and surgery groups. To determine whether the MR-specific blocker eplerenone (EPL) could improve cognitive dysfunction, we assigned other animals into the control, surgery and EPL treatment, and surgery groups. Cognitive function was detected using the Morris water maze. Serum cytokine levels were measured by ELISA, and the histopathological changes of hippocampal neurons were identified by hematoxylin/eosin and Nissl staining. Our research confirmed that anesthesia and surgical stimulation could lead to IL-1β, IL-6, and TNF-α activation and hippocampal neuronal degeneration and pathological damage. MR was upregulated in the hippocampus under cognitive impairment condition. Additionally, EPL could alleviate inflammatory activation and neuronal damage by exerting neuroprotective effects. The preclinical model of sevoflurane anesthesia/splenectomy implied that MR expression is upregulated by regulating the neuroinflammation in the brain under POCD condition. Manipulating the MR expression by EPL could improve the inflammation activation and neuronal damage.

Background Postherpetic neuralgia (PHN) is one of the most common types of chronic neuropathic pain, which seriously affects quality of the life because of pain severity and poor response to the currently available treatments. The main strategies for PHN management are medication and invasive interventional therapies; however, these approaches have many adverse effects, so it is important to find another effective and safe treatment for PHN. Methods A single-center, single-blind randomized clinical trial will evaluate 98 study participants randomized in a 1:1 ratio into control and experimental groups. The control group will receive conventional treatment including medication therapy and invasive interventional therapy. The experimental group will receive extracorporeal shockwave therapy (ESWT) in addition to conventional therapy. The primary outcome is pain intensity assessed on a visual analogue scale (VAS); the secondary outcomes are the following: quality of life assessed by the 36-Item Short-Form Health Survey (SF-36), psychological state for anxiety and depression measured by the Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS), and sleep quality measured by the Pittsburgh Sleep Quality Index (PSQI). Assessors blinded to the randomization will collect data during the intervention period at baseline and weeks 1, 4, and 12. The plasma levels of tumor necrosis factor-α and interleukin-6 will be assessed before and after ESWT to explore the biochemical mechanisms of ESWT in the treatment of PHN. Discussion This randomized controlled trial will evaluate the effectiveness and safety of ESWT in patients with PHN and thus will provide clinical evidence for its use in the management of PHN and explore the potential biochemical mechanisms of this treatment. Trial registration www.ChiCTR.org.cn, identifier: ChiCTR1900025828. Registered on 10 September 2019

Objective. To explore multiscale integrated analysis methods in identifying key regulators of esophageal cancer (ESCA). Methods. We downloaded the ESCA dataset from The Cancer Genome Atlas (TCGA) database, which contained RNA-seq data, miRNA-seq data, methylation data, and clinical phenotype information. Then, we combined ESCA-related genes from the NCBI-GENE and OMIM databases and RNA-seq dataset from TCGA to analyze differentially expressed genes (DEGs). Meanwhile, differentially expressed miRNAs (DEmiRNAs) and genes with differential methylation levels were identified. The pivot–module pairs were established using the RAID v2.0 database and TRRUST v2 database. Next, the multifactor-regulated functional network was constructed based on the above information. Additionally, gene corresponding targeted drug information was obtained from the DrugBank database. Moreover, we further screened regulators by assessing their diagnostic value and prognostic value, especially the value of distinguishing patients at TNM I stage from normal patients. In addition, the external database from the Gene Expression Omnibus (GEO) database was used for validation. Lastly, gene set enrichment analysis (GSEA) was performed to explore the potential biological functions of key regulators. Results. Our study indicated that CXCL8, CYP2C8, and E2F1 had excellent diagnostic and prognostic values, which may be potential regulators of ESCA. At the same time, the good early diagnosis ability of the three regulators also provided new insights for the diagnosis and early treatment of ESCA patients. Conclusion. We develop a multiscale integrated analysis and suggest that CXCL8, CYP2C8, and E2F1 are promising regulators with good diagnostic and prognostic values in ESCA.

BACKGROUND The long non-coding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) is expressed in solid malignant tumors. The aim of this systematic review and meta-analysis was to determine whether expression of the lncRNA SNHG1 was associated with prognosis in patients with malignancy. MATERIAL AND METHODS A literature review from Jan 1970 to July 2018 identified publications in the English language. Databases searched included: PubMed, OVID, Web of Science, the Cochrane Database, Embase, EBSCO, Google Scholar. Systematic review and meta-analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The Newcastle-Ottawa Scale (NOS) assessment tool for risk of bias was used. RESULTS Eight publications (570 patients) and eight solid tumors were identified, including osteosarcoma, colorectal cancer, hepatocellular carcinoma, non-small cell lung cancer, esophageal cancer, ovarian cancer, glioma, and gastric cancer. Meta-analysis showed that expression of the lncRNA SNHG1 was significantly correlated with reduced overall survival (OS) (HR=1.917; 95% CI, 1.58-2.31) (P

Exosomes have emerged as a novel approach for the treatment and diagnosis of cancer after RNA content was discovered in exosomes in 2007. As important meditators of intercellular communication, exosomes have become a strong focus of investigation for researchers in the past decade, as witnessed through the exponential increase of research on exosomes. The capability of exosomes to transfer functionally active cargo highlights their importance as promising biomarkers and diagnostic molecules, as well as prospective drug delivery systems. The accessibility of exosomes in nearly all biofluids additionally alludes to its unprecedented ability in various types of cancers due to its extensive impact on tumor formation and progression. This review analyzes the role of exosomal long RNA species, which is comprised of mRNA, lncRNA, and circRNA, in tumor formation and progression, with an emphasis on their potential as future diagnostic biomarkers and treatment vectors in cancer biology. Their alignment with the development of exosomal databases is further examined in this review, in view of the accumulation of studies published on exosomes in the past decade. Electronic supplementary material The online version of this article (10.1186/s12943-018-0823-z) contains supplementary material, which is available to authorized users.

Mesenchymal stem cells (MSCs) have the ability to differentiate into multiple cell types, including osteogenic, chondrogenic and adipogenic lineages. Osteogenic differentiation of MSCs plays a critical role in bone tissue engineering. Inducing MSC osteogenesis represents a potential treatment that promotes bone formation and bone regeneration. Recently, long non-coding RNA (lncRNA) was shown to participate in the occurrence and development of various diseases. Different lncRNA expression patterns can regulate the cell cycle, proliferation, metastasis, immunobiology and differentiation. With the recent extensive study of lncRNAs, an increasing number of lncRNAs are being studied in the MSC field. Furthermore, some lncRNAs have been confirmed to regulate MSC osteogenesis. Therefore, here, we review research concerning lncRNA in osteogenic differentiation of MSCs and highlight the importance of lncRNA in bone formation and bone regeneration.