Construction and Analysis of Risk Prediction Model of Eosinophilic Chronic Rhinosinusitis With Nasal Polyps: A Cross-Sectional Study in Northwest China.

OBJECTIVE: To provide guidance for clinical endotypes by constructing a risk-predictive model of eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP). DESIGN: A cross-sectional study. SETTING: Single-centre trial at tertiary medical institutions. PARTICIPANTS: A cross-sectional study included 343 CRSwNP patients divided into ECRSwNP (n = 237) and non-ECRSwNP (n = 106) groups using surgical pathology. MAIN OUTCOME MEASURES: Single-factor and multivariate analysis were used to identify statistically significant variables for constructing a nomogram, including the history of AR, hyposmia score, ethmoid sinus score, BEP and BEC. The model's performance was evaluated based on the receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA). RESULTS: Allergic rhinitis, hyposmia score, ethmoid sinus score, peripheral blood eosinophil percentage (BEP) and eosinophil count (BEC) were retained for the construction nomogram of ECRSwNP. The nomogram exhibited a certain accuracy, with an AUC of 0.897 (95% CI: 0.864-0.930), good agreement in the calibration curve and a 0.891 C-index of internal validation. Moreover, the DCA with a threshold probability between 0.0167 and 1.00 indicated a higher net benefit and greater clinical utility. CONCLUSION: The construction of a predictive risk model of ECRSwNP based on easily accessible factors could assist clinicians in more conveniently defining endotypes to make optimal diagnoses and treatment choices.

Effective Management of Polycythemia Vera With Ropeginterferon Alfa-2b Treatment.

Background: Polycythemia vera (PV) is a myeloproliferative neoplasm. Ropeginterferon alfa-2b is a new-generation polyethylene glycol-conjugated proline-interferon. It is approved for the treatment of PV at a starting dose of 100 µg (50 µg for patients receiving hydroxyurea (HU)) and dose titrations up to 500 µg by 50 µg increments. The study was aimed at assessing its efficacy and safety at a higher starting dose and simpler intra-patient dose escalation. Methods: Forty-nine patients with PV having HU intolerance from major hospitals in China were treated biweekly with an initial dose of 250 µg, followed by 350 µg and 500 µg thereafter if tolerated. Complete hematological response (CHR) was assessed every 12 weeks based on the European LeukemiaNet criteria. The primary endpoint was the CHR rate at week 24. The secondary endpoints included CHR rates at weeks 12, 36 and 52, changes of JAK2V617F allelic burden, time to first CHR, and safety assessments. Results: The CHR rates were 61.2%, 69.4% and 71.4% at weeks 24, 36, and 52, respectively. Mean allele burden of the driver mutation JAK2V617F declined from 58.5% at baseline to 30.1% at 52 weeks. Both CHR and JAK2V617F allele burden reduction showed consistent increases over the 52 weeks of the treatment. Twenty-nine patients (63.0%) achieved partial molecular response (PMR) and two achieved complete molecular response (CMR). The time to CHR was rapid and median time was 5.6 months according to central lab results. The CHRs were durable and median CHR duration time was not reached at week 52. Mean spleen index reduced from 55.6 cm2 at baseline to 50.2 cm2 at week 52. Adverse events (AEs) were mostly mild or moderate. Most common AEs were reversible alanine aminotransferase and aspartate aminotransferase increases, which were not associated with significant elevations in bilirubin levels or jaundice. There were no grade 4 or 5 AEs. Grade 3 AEs were reversible and manageable. Only one AE led to discontinuation. No incidence of thromboembolic events was observed. Conclusion: The 250-350-500 µg dosing regimen was well tolerated and effectively induced CHR and MR and managed spleen size increase. Our findings demonstrate that ropeginterferon alfa-2b at this dosing regimen can provide an effective management of PV and support using this dosing regimen as a treatment option.

Potential therapeutic targets of fibrosis in inflammatory rheumatic diseases.

Fibrosis is commonly associated with chronic rheumatic diseases, and causes substantial morbidity and mortality. Treatment of fibrosis is extremely challenging but is badly needed, as approved antifibrotic therapies fibrosis do not halt its progression, which will be discussed with a focus on pulmonary fibrosis. Findings from recent studies indicate several therapeutic targets for treating fibrosis. Interleukin-11 is emerging as a fibrogenic cytokine whose activity can be blocked with neutralizing monoclonal antibodies. Fibroblast activation protein (FAP) is highly expressed by activated fibroblasts in inflammatory and fibrotic tissues. Targeting FAP with different modalities has been extensively explored as adjunct treatment for cancer, which can also apply to treating fibrosis in rheumatic diseases.

Identification and functional analysis of novel biomarkers in adenoid cystic carcinoma.

To explore the key genes associated with the development and progression of adenoid cystic carcinoma (ACC), with the aim of exploring novel biomarkers that can better diagnose ACC, and thus better improve patient prognosis. The GSE59701 and GSE88804 datasets (containing transcriptomic data for a total of 19 normal samples and 20 tumor samples) were downloaded from the Gene Expression Omnibus (GEO) database, combined into one dataset and used to remove batch effects using the SVA algorithm. A total of 711 differentially expressed genes (DEGs) were screened by using the limma package. The metscape database (www. metascape.org) was used for gene ontology (GO) analysis and gene-specific Kyoto Genome Encyclopedia (KEGG) pathway analysis, which showed that the main enriched pathways of DEGs were kinase activity, fertility properties, extracellular matrix structural components, tryptophan metabolism, cancer pathway, PI3K-Akt signaling pathway. The STRING database was used to construct protein-protein interaction (PPI) networks for DEGs, and Cytoscape software was used to visualize the result. Lasso regression and SVM algorithm screened 3 key genes: GABBR1, ITGA9 and MLKL. The results of GSEA on key genes showed that they are mainly enriched in pathways such as cell cycle, and taste transduction mechanisms. CIBERSORT algorithm was used to analyze immune cell infiltration, the "corrplot" package was used to analyze the interaction relationships between immune cells. Spearman correlation analysis demonstrated that GABBR1, ITGA9 and MLKL were all strongly correlated with differentially expressed immune cells. Moreover, correlation analysis of key and differentially regulated genes showed that GABBR1 and MLKL were significantly correlated with MYB and TP53, respectively. In conclusion, GABBR1, ITGA9 and MLKL affect the progression of ACC, where GABBR1 and MLKL may regulate ACC through MYB and TP53, and the relationship between ITGA9 and ECM and PI3K-Akt may have some influence on the development of ACC.

Genomic landscape and expression profile of consensus molecular subtype four of colorectal cancer.

Background: Compared to other subtypes, the CMS4 subtype is associated with lacking of effective treatments and poorer survival rates. Methods: A total of 24 patients with CRC were included in this study. DNA and RNA sequencing were performed to acquire somatic mutations and gene expression, respectively. MATH was used to quantify intratumoral heterogeneity. PPI and survival analyses were performed to identify hub DEGs. Reactome and KEGG analyses were performed to analyze the pathways of mutated or DEGs. Single-sample gene set enrichment analysis and Xcell were used to categorize the infiltration of immune cells. Results: The CMS4 patients had a poorer PFS than CMS2/3. CTNNB1 and CCNE1 were common mutated genes in the CMS4 subtype, which were enriched in Wnt and cell cycle signaling pathways, respectively. The MATH score of CMS4 subtype was lower. SLC17A6 was a hub DEG. M2 macrophages were more infiltrated in the tumor microenvironment of CMS4 subtype. The CMS4 subtype tended to have an immunosuppressive microenvironment. Conclusion: This study suggested new perspectives for exploring therapeutic strategies for the CMS4 subtype CRC.

Quantification of Tumor Abnormal Proteins in the Diagnosis and Postoperative Prognostic Evaluation of Gastric Cancer.

Background: Abnormal glycosylation of proteins has been identified in almost all types of cancers and is closely related to the cancer progression, metastasis, and survival of cancer patients. This study was to explore the values of serum tumor abnormal protein (TAP), an abnormal glycochain protein, in the diagnosis and prognosis of gastric cancer (GC). Methods: A total of 335 GC patients were included as the study group, and another 335 subjects served as the control group. Tumor abnormal protein expression was compared between the 2 groups. Correlation analysis was used to assess the correlations of TAP with clinicopathological factors. Gastric cancer patients were divided into training set and test set at a ratio of 2:1. Univariate and multivariate Cox regression analyses in training set were used to evaluate the prognostic significance of TAP in GC patients and explore the independent risk factors for overall survival (OS) and disease-free survival (DFS) to establish a prognostic model, followed by testing of the model. According to the median of TAP, 335 GC patients were divided into 2 groups to plot the survival curves of OS and DFS. Results: Tumor abnormal protein expression in the study group was significantly higher than in the control group. Taking the best cut-off value of TAP (110.128 µm2) as the diagnostic criteria for GC, the sensitivity and specificity of TAP were 83.58% and 97.61%, respectively, and the area under the receiver operating characteristics (ROC) curve was 0.935, which was not inferior to computed tomography (CT). Tumor abnormal protein expression was an independent risk factor for OS and DFS. The prognostic predictive value of TAP was better than that of pathological stage in GC patients. The model with TAP was effective in predicting prognosis. Conclusion: Tumor abnormal protein is an effective indicator for early screening and prognostic evaluation of GC and can also assist the clinical diagnosis and treatment of GC.

A model to predict a risk of allergic rhinitis based on mitochondrial DNA copy number.

PURPOSE: To determine whether mitochondrial DNA copy number (mtDNA-CN) is associated with allergic rhinitis (AR), and further establish a nomogram model for the early diagnosis of AR. METHODS: We carried out a case-control study involving a total of 134 subjects, including 66 healthy controls and 68 AR patients. The mtDNA-CN in peripheral blood of all subjects was detected by real-time fluorescence quantitative polymerase chain reaction, and general information of patients was recorded. And, least absolute shrinkage selection operator (LASSO) regression was used to screen clinically significant variables, which were substituted into a logistic regression analysis to determine independent risk factors. Next, a nomogram model was developed for the risk prediction of AR. Then, internal validation was performed with the bootstrap resampling. Ultimately, the clinical benefit and validity of the nomogram were assessed by receiver operating characteristic (ROC) curve, bias-corrected curve, and decision curve analysis (DCA). RESULTS: MtDNA-CN and total IgE were determined as independent risk factors of AR. The final model achieved an area under the ROC curve (AUC) of 0.869, and the DCA curve demonstrated that the nomogram was clinically beneficial for practical application. CONCLUSION: An increase of the mtDNA-CN was linked to the occurrence risk of AR. The nomogram prediction model based on mtDNA-CN showed the potential clinical utility in improving risk prediction and providing new insights for exploring the pathogenesis of AR.

Glycerophospholipid metabolism is involved in rheumatoid arthritis pathogenesis by regulating the IL-6/JAK signaling pathway.

To explore the metabolic mechanism of differential plasma interleukin (IL)-6 expression in patients with rheumatoid arthritis (RA). A total of 240 RA patients were enrolled in the non-target metabolomics study cohort and 69 healthy volunteers were included as healthy controls (HCs). Plasma IL-6 levels were detected by electrochemiluminescence assay. Plasma metabolites were detected by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Patients with active RA (n = 20) and remissive RA (n = 20) and 20 HCs were enrolled in the targeted validation cohort. Metabolites identified by non-target metabolomics were quantitatively analyzed by ultra-performance liquid chromatography-triple quadrupole tandem mass spectrometry. Effects of 1-oleoyl-sn-glycero-3-phosphocholine (OGPC) associated with IL-6 on MH7A cells were assessed. After 24-h or 48-h induction by TNF-α, the supernatants were collected for IL-6 quantification by enzyme-linked immunosorbent assay. Furthermore, Western blot was performed to investigate the relative JAK2 and p-JAK2 expressions. With an increasing IL-6 level, OGPC shown to be related to the glycerophospholipid metabolism pathway by Kyoto Encyclopedia of Genes and Genomes analysis displayed a significant decrease. In the validating RA cohort, the OGPC concentrations in remissive RA group and active RA group decreased compared with HC group. OGPC down-regulated IL-6 secretion and p-JAK2 expression in TNF-α-induced MH7A cells in vitro. In conclusion, glycerophospholipid metabolism is the main metabolic pathway associated with the differential IL-6 expression in RA patients. The down-regulated OGPC is a promoting factor for the increased IL-6 plasma level in RA patients, which further affects the downstream JAK signaling pathway.

Identification of hub genes in rheumatoid arthritis through an integrated bioinformatics approach.

BACKGROUND: Rheumatoid arthritis (RA) is a common chronic autoimmune disease characterized by inflammation of the synovial membrane. However, the etiology and underlying molecular events of RA are unclear. Here, we applied bioinformatics analysis to identify the key genes involved in RA. METHODS: GSE77298 was downloaded from the Gene Expression Omnibus (GEO) database. We used the R software screen the differentially expressed genes (DEGs). Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway were analyzed by using the DAVID online tool. The STRING database was used to analyze the interaction of differentially encoded proteins. PPI interaction network was divided into subnetworks using MCODE algorithm and was analyzed using Cytoscape. Gene set enrichment analysis (GSEA) was performed to identify relevant biological functions. qRT-PCR analysis was also performed to verify the expression of identified hub DEGs. RESULTS: A total of 4062 differentially expressed genes were selected, including 1847 upregulated genes and 2215 downregulated genes. In the biological process, DEGs were mainly concentrated in the fields of muscle filament sliding, muscle contraction, intracellular signal transduction, cardiac muscle contraction, signal transduction, and skeletal muscle tissue development. In the cellular components, DEGs were mainly concentrated in the parts of cytosol, Z disk, membrane, extracellular exosome, mitochondrion, and M band. In molecular functions, DEGs were mainly concentrated in protein binding, structural constituent of muscle, actin binding, and actin filament binding. KEGG pathway analysis shows that DEGs mainly focuses on pathways about lysosome, Wnt/ß-catenin signaling pathway, and NF-κB signaling pathway. CXCR3, GNB4, and CXCL16 were identified as the core genes that involved in the progression of RA. By qRT-PCR analysis, we found that CXCR3, GNB4, and CXCL16 were significantly upregulated in RA tissue as compared to healthy controls. CONCLUSION: In conclusion, DEGs and hub genes identified in the present study help us understand the molecular mechanisms underlying the progression of RA, and provide candidate targets for diagnosis and treatment of RA.

Clinical Anatomy of Human Donor C7 Nerve Roots for Surgical Transfer in Patients with Spastic Arm Paralysis.

BACKGROUND: Contralateral C7 (CC7) nerve transfer has successfully restored hand function in patients with spastic hemiplegia from chronic central nervous system injuries. However, little is known about the morphology and anatomy of the donor C7 nerve root in patients undergoing this procedure. This study quantified intraoperative measurements of donor C7 nerve roots during CC7 transfer surgery for spastic hemiplegia in patients treated at a high-volume center to describe observed anatomical variations for successful direct anastomosis. METHODS: A database of images from 21 patients (2 females, 19 males) undergoing CC7 surgery was searched for photographic data that contained a standard ruler measuring donor C7 nerve root length after surgical sectioning and before transfer. Two independent observers analyzed these images and recorded C7 nerve root diameter, length, and branch lengths. RESULTS: Mean (SD) values of donor C7 nerve measurements were length, 53.5 (8.0) mm; diameter, 5.1 (0.9) mm; branch length following surgical sectioning, 18.3 (6.3) mm. Right-sided donor C7 nerve roots yielded significantly longer branches compared with left-sided donor C7 nerve roots (P = 0.01). Other patient factors such as age, sex, or laterality of brain injury did not influence intraoperative anatomy. CONCLUSIONS: We report detailed intraoperative measurements of the donor C7 root during CC7 nerve transfer for spastic hemiplegia. These findings describe existing variation in surgical C7 nerve root anatomy in patients undergoing this procedure and may serve as a general reference for the expected donor C7 length in successful direct anastomosis.

ANCA-associated vasculitis overlaps with systemic sclerosis: a case report and literature review.

BACKGROUND: Systemic sclerosis (SSc) and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) both affect the kidney and may cause renal failure. Treatment of AAV is dramatically different from that of SSc renal crisis (SRC). Kidney biopsy is not recommended for diagnosing SRC, but it is the only reliable diagnostic method for AAV. CASE PRESENTATION: Here, a 49-year-old male patient with diffuse SSc presented with acute renal insufficiency and detectable ANCA with myeloperoxidase-specific antibodies. A renal biopsy revealed necrotizing glomerulonephritis and was consistent with AAV. This finding confirms the existence of AAV and SSc overlap syndrome. The patient was treated with intravenous methylprednisolone, intravenous cyclophosphamide, tandem membrane plasma exchange, and hemodialysis. After treatment, his clinical symptoms remained stable, and his creatinine and C-reactive protein (CRP) levels have remained normalized as of his most recent follow-up after hospital discharge. CONCLUSIONS: AAV can overlap with SSc; although this condition is rare, it is associated with considerable morbidity and mortality. Therefore, it is critical to recognize AAV in the setting of worsening renal function due to SSs and provide appropriate treatment. Several clinical features are suggestive of AAV rather than SRC, but renal biopsy is required for accurate diagnosis.

Ticagrelor prevents tumor metastasis via inhibiting cell proliferation and promoting platelet apoptosis.

Tumor cells can activate platelets, which in turn facilitate tumor cell survival and dissemination. Platelets inhibition or blocking platelet-tumor cell interactions has become a strategy to suppress tumor progression. In this study, we investigated the effect of ticagrelor, a new antiplatelet drug, on tumor cell proliferation and metastasis. Our results show that ticagrelor not only inhibits the proliferation, migration, and invasion of B16F10 and Lewis lung carcinoma cells but also induces platelet apoptosis. In addition, we find that apoptosis of the platelet cells is dose dependent. Further, the result of in-vivo experiments proved that ticagrelor treatment decreased the tumor metastasis. The results of this study demonstrate that ticagrelor may be a potential anti-tumor agent for tumor metastasis.

CAG regimen for refractory or relapsed adult T-cell acute lymphoblastic leukemia: A retrospective, multicenter, cohort study.

Adult patients with relapsed or refractory T-cell acute lymphoblastic leukemia (R/R-T-ALL) have extremely poor prognosis, representing an urgent unmet medical need. Finding an optimal salvage regimen to bridge transplantation is a priority. The CAG (cytarabine, aclarubicin, and G-CSF) regimen was initially used by one group in China, showing unexpectedly promising results in 11 R/R-T-ALL patients. Here, we report the multicenter results of 41 patients who received the CAG regimen as salvage therapy. After one cycle of the CAG regimen, complete remission and partial remission were achieved in 33 (80.5%) and two (4.9%) patients, respectively. Failure to respond was observed in six patients (14.6%). Early T-cell precursor (ETP) (n = 26) and non-ETP (n = 15) patients had a similar CR rate (80.8% vs 80.0%, P = .95). Among 41 patients, allo-HSCT was successfully performed in 27 (66%) patients (22 in CR and 5 in non-CR). With a median follow-up time of 12 months, the estimated 2-year overall survival and event-free survival were 68.8% (95% CI, 47.3%-83.0%) and 56.5% (95% CI, 37.1%-71.9%), respectively. The CAG regimen was well-tolerated, and no early death occurred. Our multicenter results show that the CAG regimen is highly effective and safe, representing a novel choice for adult patients with R/R-T-ALL and providing a better bridge to transplantation.

SETD2 deficiency accelerates MDS-associated leukemogenesis via S100a9 in NHD13 mice and predicts poor prognosis in MDS.

SETD2, the histone H3 lysine 36 methyltransferase, previously identified by us, plays an important role in the pathogenesis of hematologic malignancies, but its role in myelodysplastic syndromes (MDSs) has been unclear. In this study, low expression of SETD2 correlated with shortened survival in patients with MDS, and the SETD2 levels in CD34+ bone marrow cells of those patients were increased by decitabine. We knocked out Setd2 in NUP98-HOXD13 (NHD13) transgenic mice, which phenocopies human MDS, and found that loss of Setd2 accelerated the transformation of MDS into acute myeloid leukemia (AML). Loss of Setd2 enhanced the ability of NHD13+ hematopoietic stem and progenitor cells (HSPCs) to self-renew, with increased symmetric self-renewal division and decreased differentiation and cell death. The growth of MDS-associated leukemia cells was inhibited though increasing the H3K36me3 level by using epigenetic modifying drugs. Furthermore, Setd2 deficiency upregulated hematopoietic stem cell signaling and downregulated myeloid differentiation pathways in the NHD13+ HSPCs. Our RNA-seq and chromatin immunoprecipitation-seq analysis indicated that S100a9, the S100 calcium-binding protein, is a target gene of Setd2 and that the addition of recombinant S100a9 weakens the effect of Setd2 deficiency in the NHD13+ HSPCs. In contrast, downregulation of S100a9 leads to decreases of its downstream targets, including Ikba and Jnk, which influence the self-renewal and differentiation of HSPCs. Therefore, our results demonstrated that SETD2 deficiency predicts poor prognosis in MDS and promotes the transformation of MDS into AML, which provides a potential therapeutic target for MDS-associated acute leukemia.

A four-gene signature for prognosis in breast cancer patients with hypermethylated IL15RA.

Previous studies have revealed that upregulation of interleukin 15 receptor α (IL15RA) contributes to improved prognosis of breast cancer. The present study aimed to elucidate the molecular mechanisms underlying the antitumor effect induced by IL15RA upregulation, and to identify a gene signature capable of predicting the survival of patients with breast cancer. Using paired gene expression and methylation data of breast cancer samples from The Cancer Genome Atlas data portal, differentially expressed genes (DEGs) were identified in hypermethylated and hypomethylated IL15RA breast cancer samples. Furthermore, a gene signature-based risk-scoring model was developed according to the Cox regression coefficients of survival-associated DEGS. The gene signature was applied to classify patients with breast cancer and hypermethylated IL15RA into two risk groups via Kaplan-Meier survival analysis of overall survival (OS) time. Functional enrichment analysis was conducted to decipher the biological roles of the DEGs between the two risk groups. A total of 326 DEGs were present in the hypomethylation and hypermethylation samples compared with in the normal samples. A four-gene signature [SH3 and cysteine rich domain 2 (STAC2), proline rich 11 (PRR11), homeobox C11 (HOXC11) and nucleolar and spindle associated protein 1 (NUSAP1)] was identified as able to successfully separate patients with breast cancer and hypermethylated IL15RA into two risk groups with significantly different OS time. The signature revealed similar predictive performance in an independent set. Significant enrichment of the 'receptor interaction' and 'cell adhesion molecules (CAM)' pathways, which involved the DEGs, occurred between the two risk groups. These findings suggested that IL15RA may participate in the regulation of STAC2, PRR11, HOXC11, NUSAP1, and 'ECM-receptor interaction' and 'cell adhesion molecules' pathways, and therefore in the suppression of breast cancer development and progression. The four-gene signature may have potential prognostic value for breast cancer.

Tubeimoside-1 inhibits the proliferation and metastasis by promoting miR-126-5p expression in non-small cell lung cancer cells.

Tubeimoside-1 (TBMS1) possesses broad anticancer activities, including the cytostatic and anti-angiogenesis effects in lung cancer. However, the effect of TBMS1 on the metastasis of non-small cell lung cancer (NSCLC) cells and the potential underlying mechanism remain unclear. In the present study, a cell counting kit-8 assay revealed that TBMS1 suppressed the proliferation of NCI-H1299 cells significantly, particularly following 48 h of treatment. Further studies showed that TBMS1 notably enhanced the apoptosis, and inhibited the migration and invasion of NCI-H1299 cells upon treatment for 48 h. A total of 14 NSCLC tissues and 14 normal adjacent tissues were collected, reverse transcription-quantitative polymerase chain reaction revealed decreased expression of microRNA (miR)-126-5p in NSCLC tissues compared with adjacent NSCLC tissues, which was reversed following TBMS1 administration in NCI-H1299 cells. The overexpression of miR-126-5p induced by TBMS1 was demonstrated to target and downregulate vascular endothelial growth factor (VEGF)-A. Simultaneously, the expression of VEGF-R2 was reduced notably, along with a significant declined in the phosphorylation levels of dual specificity mitogen-activated protein kinase kinase 1 and extracellular signal-regulated kinase (ERK)1/2. Overall, the aforementioned results indicated that TBMS1 inhibited the proliferation and metastasis, and promoted the apoptosis of NCI-H1299 cells, which may be mediated by overexpressing miR-126-5p, which inactivates the VEGF-A/VEGFR2/ERK signaling pathway. Therefore, TBMS1 may be a promising drug for prevention and treatment of NSCLC.

Genes associated with inflammation and the cell cycle may serve as biomarkers for the diagnosis and prognosis of acute myocardial infarction in a Chinese population.

The present study aimed to identify biomarkers for the clinical diagnosis of acute myocardial infarction (AMI) in a Chinese population using microarray data collected from the Gene Expression Omnibus database under accession number GSE97320. This included the peripheral blood samples of three patients with AMI and three controls. Differentially expressed genes (DEGs) were identified using the limma package and protein­protein interaction networks were constructed using data from the Search Tool for the Retrieval of Interacting Genes database, followed by module analysis to screen for hub genes. Functional enrichment analyses were performed using the Database for Annotation, Visualization and Integrated Discovery. The identified genes were verified by overlapping with the target genes of microRNAs (miRs) known to be associated with AMI, as well as the DEGs identified in other AMI datasets, including GSE24519, GSE34198 and GSE48060. As a result, 752 DEGs (449 upregulated and 303 downregulated) were identified in the GSE97320 dataset. The upregulated DEGs were predicted to participate in inflammatory pathways, including the toll­like receptor (TLR) signaling pathway, including ras­related C3 botulinum toxin substrate 1 (RAC1), TLR4, C­C motif chemokine receptor (CCR)1; cytokine­cytokine receptor interaction, including signal transducer and activator of transcription (STAT)3; chemokine signaling pathway, including CCR10; pathways associated with cancer, including colony stimulating factor 3 receptor (CSF3R); and leukocyte transendothelial migration, including matrix metallopeptidase 9 (MMP9). The downregulated DEGs were associated with the cell cycle, including alstrom syndrome protein 1 (ALMS1). These conclusions were made following functional analysis of the genes in the three identified modules. MMP9, TLR4, STAT3, CCR1 and ALMS1 were regulated by miR­21­5p, whereas RAC1 was regulated by miR­30c­5p. A comparison among the four datasets confirmed the roles of CSF3R and CCR10. HtrA serine peptidase 1 (HTRA1) was the only gene associated with both mortality and recurrence. In conclusion, inflammation­associated genes, including STAT3, CCR1, RAC1, MMP9, CCR10, CSF3R and HTRA1, as well as cell cycle­associated genes such as ALMS1, may be biomarkers for the diagnosis and prognosis of AMI in Chinese people.

Antitumor effects of Tubeimoside-1 in NCI-H1299 cells are mediated by microRNA-126-5p-induced inactivation of VEGF-A/VEGFR-2/ERK signaling pathway.

Tubeimoside-1 (TBMS1), a triterpenoid saponin isolated from the tuber of Bolbostemma paniculatum (Maxim) Franquet, serves an universal suppressive role in multiple cancer types, including lung cancer. However, the mechanism involved in non­small cell lung cancer (NSCLC) cells by which TBMS1 elicits its antitumor effects is not yet comple-tely understood. The present study indicated that 10 µmol/l TBMS1 significantly enhanced apoptosis and notably blocked the migration and invasion of NCI­H1299 cells. These effects were reversed following transfection with miR­126­5p inhi-bitor into TBMS1­treated NCI­H1299 cells. Vascular endo-thelial growth factor-A (VEGF­A) is a target gene for miR­126­5p. Notably, results suggested that the downregulated VEGF­A and VEGFR­2 in TBMS1­treated NCI­H1299 cells were upregulated after inhibiting miR­126­5p, and overexpression of VEGF­A or VEGFR­2 could significantly reduce apoptosis and promote the migration and invasion of TBMS1­treated NCI­H1299 cells. Furthermore, TBMS1 combined with TBHQ (an ERK activator) dramatically suppressed TBMS1­induced apoptosis and stimulated TBMS1­reduced migration and invasion in NCI­H1299 cells, suggesting that TBMS1 inhibits the ERK signaling pathway and represses the growth and metastasis of NCI­H1299 cells. Further study demonstrated that either inhibiting miR­126­5p or overexpressing VEGF­A and VEGFR­2 in TBMS1­treated NCI­H1299 cells elevated the mRNA expression levels and phosphorylation levels of MEK1, as well as ERK. To conclude, TBMS1 increases miR­126­5p expression, whereas overexpressing miR­126­5p inactivates VEGF­A/VEGFR­2/ERK signaling pathway, which ultimately actuates the pro­apoptotic and anti­metastatic effects in NCI­H1299 cells. Therefore, the present findings provide a theoretical foundation for TBMS1 as a potential candidate in NSCLC treatment.

Clinical Features and Prognosis Analysis of Hodgkin Lymphoma: A Multicenter Retrospective Study Over a Decade of Patients in China.

OBJECTIVE: There is little information available regarding Chinese patients with Hodgkin lymphoma (HL). We analyzed the clinical features, outcome, and prognostic factors of Chinese patients with HL, aiming to establish a new risk model for better risk-adapted therapeutic strategy. PATIENTS AND METHODS: Patients with newly diagnosed HL at 4 medical centers from January 2000 to August 2014 were recruited. RESULTS: A total of 150 patients were reviewed. The median age was 30 years (range, 15-91 years). At completion of initial therapy, 73.65% of patients achieved complete remission. The 5-year event-free survival (EFS) of the entire cohort was 61.1%, the overall survival was 84.7%, and the disease-free survival was 78.8%. B symptoms, extranodal involvement, and International Prognostic Score ≥ 3 remained as independent prognostic factors of EFS. Patients who failed to reach complete remission on interim positron emission tomography/computed tomography or computed tomography had a significantly worse outcome than those who did. A new risk model incorporating traditional risk factors and interim response stratified patients into 3 classes, with a 5-year EFS of 100%, 83.1%, and 33.1%, respectively (P < .0001). CONCLUSIONS: General clinical features were comparable with those of Western patients, whereas therapeutic outcomes were slightly inferior. The novel risk assessment model showed potential as a more powerful prognostic tool by identifying 3 subsets of patients with significantly distinct outcomes, which warrants further validations.