Stress hyperglycemia ratio and neutrophil to lymphocyte ratio are reliable predictors of new-onset atrial fibrillation in patients with acute myocardial infarction.

Background: The occurrence of new-onset atrial fibrillation (NOAF) post-acute myocardial infarction (AMI) is associated with worse outcomes. In this study, we sought to assess the predictive effect of stress hyperglycemia ratio (SHR) and neutrophil to lymphocyte ratio (NLR) to predict NOAF in patients with AMI. Materials and methods: We recruited 3,194 individuals with AMI but free of atrial fibrillation (AF). AMI cases were stratified into groups according to SHR and NLR quartiles and were further categorized based on diabetes status. High SHR and high NLR were defined as the highest quartile of SHR and NLR. A nomogram incorporating risk factors for NOAF was constructed using multivariate logistic regression analyses. The performance of the novel nomogram was tested for predictive performance, agreement between the actual and predicted probability, and clinical utility using area under the curve (AUC), bootstrapped calibration curves, and decision curve analysis, respectively. Result: A total of 245 (7.67%) patients developed NOAF post-AMI. The NOAF cases had higher values of SHR and NLR than non-NOAF patients after AMI regardless of diabetes status. After adjusting for potential confounders, high SHR and NLR were independently associated with NOAF post-AMI. Moreover, the novel nomogram incorporating high NLR and high SHR for NOAF risk estimation in patients with AMI showed satisfactory performance assessed by the AUC, calibration curves, decision curve analysis. Conclusion: SHR and NLR were independently associated with NOAF in AMI patients. The constructed novel nomogram that incorporates SHR and NLR might assist in NOAF risk stratification post-AMI.

Silencing GnT-V reduces oxaliplatin chemosensitivity in human colorectal cancer cells through N-glycan alteration of organic cation transporter member 2.

Organic cation transporter member 2 (OCT2) is an N-glycosylated transporter that has been shown to be closely associated with the transport of antitumor drugs. Oxaliplatin, a platinum-based drug, is used for the chemotherapy of colorectal cancer (CRC). However, oxaliplatin resistance is a major challenge in the treatment of advanced CRC. The aim of the present study was to better understand the mechanism underlying the chemosensitivity of CRC cells to oxaliplatin. The present study describes a potential novel strategy for enhancing oxaliplatin sensitivity involving the glycosylation of this drug transporter, specifically the modification of ß-1,6-N-acetylglucosamine (GlcNAc) residues by N-acetylglucosaminyltransferase V (GnT-V). The results revealed that the downregulation of GnT-V inhibited the oxaliplatin chemosensitivity of CW-2 cells. Furthermore, the knockdown of GnT-V caused a marked reduction in the presence of ß-1,6-GlcNAc structures on OCT2 and decreased the localization of OCT2 in the cytomembrane, which were associated with a reduced uptake of oxaliplatin in wild-type and oxaliplatin-resistant CW-2 cells. Overall, the study provides novel insights into the molecular mechanism by which GnT-V regulates the chemosensitivity to oxaliplatin, which involves the modulation of the drug transporter OCT2 by N-glycosylation in CRC cells.

Erratum: Isolation of circulating tumor cells in patients undergoing surgery for esophageal cancer and a specific confirmation method.

[This corrects the article DOI: 10.3892/ol.2019.10017.].

Salivary Microbial Dysbiosis is Associated with Systemic Inflammatory Markers and Predicted Oral Metabolites in Non-Small Cell Lung Cancer Patients.

An increasing number of studies have suggested the dysbiosis of salivary microbiome has been linked to the advancement of multiple diseases and proved to be helpful for the diagnosis of them. Although epidemiological studies of salivary microbiota in carcinogenesis are mounting, no systemic study exists regarding the oral microbiota of non-small cell lung cancer (NSCLC) patients. In this study, we presented the characteristics of the salivary microbiota in patients from NSCLC and healthy controls by sequencing of the 16S rRNA microbial genes. Our result revealed distinct salivary microbiota composition in patients from NSCLC compared to the healthy controls. As principal co-ordinates analysis (PCoA) showed, saliva samples clearly differed between the two groups, considering the weighted (p = 0.001, R2 = 0.17), and unweighted (p = 0.001, R2 = 0.25) UniFrac distance. Phylum Firmicutes (31.69% vs 24.25%, p < 0.05) and its two genera Veillonella (15.51%% vs 9.35%, p < 0.05) and Streptococcus (9.96% vs 6.83%, p < 0.05) were strongly increased in NSCLC group compared to the controls. Additionally, the relative abundances of Fusobacterium (3.06% vs 4.92%, p = 0.08), Prevotella (1.45% vs 3.52%, p < 0.001), Bacteroides (0.56% vs 2.24%, p < 0.001), and Faecalibacterium (0.21% vs 1.00%, p < 0.001) in NSCLC group were generally decreased. Furthermore, we investigated the correlations between systemic inflammation markers and salivary microbiota. Neutrophil-lymphocyte ratio (NLR) positively correlated with the Veillonella (r =0.350, p = 0.007) and lymphocyte-monocyte ratio (LMR) negatively correlated with Streptococcus (r =-0.340, p = 0.008). Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways inferred by phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) showed that pathways related to xenobiotics biodegradation and metabolism (p < 0.05) and amino acid metabolism (p < 0.05) were enriched in the NSCLC group. Folate biosynthesis (p < 0.05) significantly decreased in NSCLC group. The specific correlations of clinical systemic inflammation markers and predicted KEGG pathways also could pronounce a broad understanding of salivary microbiota in patients with NSCLC. Moreover, our study extended the new sight into salivary microbiota-targeted interventions to clinically improve the therapeutic strategies for salivary dysbiosis in NSCLC patients. Further investigations of the potential mechanism of salivary microbiota in the progression of NSCLC are still in demand.

Isolation of circulating tumor cells in patients undergoing surgery for esophageal cancer and a specific confirmation method.

The clinical significance of circulating tumor cells (CTCs) in patients with esophageal squamous cell carcinoma (ESCC) who have undergone radical surgery was investigated. A novel confirmation method for identifying CTCs or circulating tumor microemboli (CTM) in ESCC was also investigated. Blood samples from 55 patients with ESCC were collected 1-3 days prior to surgery and 7 days post-surgery. All patients underwent curative thoracic esophagectomy and lymphadenectomy. Blood samples from 20 healthy volunteers were obtained as controls. Isolation by size of epithelial tumor cells (ISET) was performed also. The overall CTC detection rate was 52.7% preoperatively and 49.1% postoperatively. The presence of CTCs correlated with the Tumor-Node-Metastasis stage and the Log odds of positive lymph nodes. No significant difference in perioperative CTC transformation was discovered between the thoracoscopic and laparoscopic approach, and the open approach. The P40+/cluster of differentiation (CD)45- phenotype was confirmed in the CTCs and CTM. ISET appeared to have high sensitivity for detecting CTCs within ESCC patients. Immunofluorescence staining for CD45 and P40 was a specific, accurate and convenient method for confirming the presence of CTCs or CTM in patients with ESCC, and is strongly recommended as a supplement to morphological analysis.

Alterations of fecal bacterial communities in patients with lung cancer.

Emerging evidence suggests the microbiome may affect a number of diseases, including lung cancer. However, the direct relationship between gut bacteria and lung cancer remains uncharacterized. In this study, we directly sequenced the hypervariable V1-V2 regions of the 16S rRNA gene in fecal samples from patients with lung cancer and healthy volunteers. Unweighted principal coordinate analysis (PCoA) revealed a clear difference in the bacterial community membership between the lung cancer group and the healthy control group. The lung cancer group had remarkably higher levels of Bacteroidetes, Fusobacteria, Cyanobacteria, Spirochaetes, and Lentisphaerae but dramatically lower levels of Firmicutes and Verrucomicrobia than the healthy control group (P < 0.05). Despite significant interindividual variation, eight predominant genera were significantly different between the two groups. The lung cancer group had higher levels of Bacteroides, Veillonella, and Fusobacterium but lower levels of Escherichia-Shigella, Kluyvera, Fecalibacterium, Enterobacter, and Dialister than the healthy control group (P < 0.05). Most notably, correlations between certain specific bacteria and serum inflammatory biomarkers were identified. Our findings demonstrated an altered bacterial community in patients with lung cancer, providing a significant step in understanding the relationship between gut bacteria and lung cancer. To our knowledge, this is the first study to evaluate the correlations between certain specific bacteria and inflammatory indicators. To better understand this relationship, further studies should investigate the underlying mechanisms of gut bacteria in lung cancer animal models.

Curcumin induces apoptosis and inhibits angiogenesis in murine malignant mesothelioma.

Malignant pleural mesothelioma (MPM) is a rare form of cancer that is associated with asbestos exposure. Unfortunately, current therapies have limited efficacy. Previous studies have indicated that curcumin exerts antiproliferative and antitumor effects, and has low toxicity. The present study aimed to evaluate the anticancer effects of curcumin on the RN5 MPM cell line. The inhibitory effects of curcumin on cell viability were determined using the sulforhodamine B assay. In addition, cell cycle progression was analyzed by propidium iodide (PI) staining and flow cytometry, and curcumin­induced apoptosis was measured by Annexin V/PI double staining. The translocation of apoptosis-inducing factor (AIF) was assessed by western blotting and immunofluorescence, and the expression levels of the phosphoinositide 3-kinase (PI3K)-AKT serine/threonine kinase (Akt)­mammalian target of rapamycin (mTOR) signaling pathway proteins and mitochondria-associated proteins were evaluated by western blotting. In vivo antitumor effects were evaluated in a subcutaneous murine model. Briefly, tumors were harvested from the mice, and immunohistochemistry was conducted to evaluate cell proliferation, apoptosis and angiogenesis. The results indicated that curcumin inhibited RN5 cell viability and induced apoptotic cell death. In addition the findings suggested that curcumin-induced cell apoptosis occurred via the mitochondrial pathway, and caspase­independent and AIF-dependent pathways. Further analysis revealed that curcumin may act as a PI3K-Akt-mTOR signaling pathway inhibitor by downregulating PI3K, p-Akt, p-mTOR and p-p70 ribosomal protein S6 kinase. Furthermore, curcumin inhibited tumor angiogenesis in vivo. In conclusion, curcumin may be potent enough to be developed as a novel therapeutic agent for the treatment of MPM.

GnT-V promotes chemosensitivity to gemcitabine in bladder cancer cells through ß1,6 GlcNAc branch modification of human equilibrative nucleoside transporter 1.

Human equilibrative nucleoside transporter 1 (hENT1) transports nucleoside analogue drugs across cellular membranes and is necessary for the uptake of many anti-tumor drugs. Gemcitabine is a frontline agent of chemotherapy for bladder cancer despite its limited efficacy due to chemoresistance, there is an acute need to decipher mechanisms underlying chemosensitivity to gemcitabinein in bladder cancer cells. Here we report a novel role for N-acetylglucosaminyltransferase V (GnT-V) in gemcitabine chemosensitivity. In this study, we found that GnT-V expression affected cell death rate to gemcitabine in different bladder cancer cells and down-regulation of GnT-V inhibited the gemcitabine sensitivity with time and dose dependent way in T24 cells. Moreover, mechanistic investigations showed that silencing GnT-V caused dramatic decrease of ß1,6 GlcNAc structure on hENT1 leading to apparently decreased accumulation of hENT1 at plasma membrane, and therefore result in less uptake of gemcitabine in T24/shRNA cells. Together, our present study indicated that GnT-V enhances gemcitabine chemosensitivity via modulation of hENT1 N-glycosylation and transport activity in T24 cells, providing new insights into how N-glycosylation drives antitumor drug sensitivity during chemotherapy for patients with cancer.

Two single-nucleotide polymorphisms of the RELN gene and symptom-based and developmental deficits among children and adolescents with autistic spectrum disorders in the Tianjin, China.

Increasing evidence has revealed that genetic variants in Reelin (RELN) gene, especially single-nucleotide polymorphisms (SNPs), correlate with autistic spectrum disorders (ASD) risk; however, no consensus have been reached. This study aimed to provide additional evidence for the association between two SNPs of RELN (i.e., rs736707, rs2229864) and ASD risk, as well as the relationship between RELN gene and symptom-based and developmental deficits of ASD patients in Chinese Han children and adolescents. 157 ASD subjects and 256 typical development (TD) controls were genotyped by TaqMan® genotyping assay. ASD patients were assessed by Childhood Autism Rating Scale (CARS), Autism Behavior Checklist (ABC), and Early Childhood Development Questionnaire (ECDQ). We found that SNP rs2229864 was associated with the genetic predisposition of ASD, whereas a negative association between SNP rs2229864 and symptom-based and developmental features was detected. In contrast, RELN rs736707 correlated with the sensory subscale of the ABC, the relating subscale of the ABC and the total score of ABC, although we did not detect a significant association between SNP rs736707 and ASD risk. Furthermore, a significant rs736707-rs2229864 haplotype was detected. Individuals with a CC haplotype were more likely to have ASD, but individuals with a CT haplotype had more chance be TD controls. Further studies using more samples and including more gene variants in RELN are warranted to confirm our results.

Is the Wedged Insole an Effective Treatment Option When Compared with a Flat (Placebo) Insole: A Systematic Review and Meta-Analysis.

BACKGROUND: Using the lateral wedge insole is a conservative management strategy for knee osteoarthritis. The theoretical basis for this intervention is to correct femorotibial angle, thereby reducing pain and optimising function. OBJECTIVE: This systematic review evaluates the evidence on the effectiveness of wedge insole compared with flat insole for the treatment of knee osteoarthritis. METHODS: A systematic review was performed, searching published (MEDLINE, EMBASE, CNKI, Cochrane Library, and Web of Science) and unpublished literature from their inception to April 2018. Randomized controlled trials (RCTs) that compared the use of wedge insole with a flat insole were included. Risk of bias and clinical relevance were assessed, and outcomes were analysed through meta-analysis. RESULT: From a total of 413 citations, 8 studies adhered to the a priori eligibility criteria. The WOMAC pain was shown to be statistically nonsignificant change with the use of wedge insole (SMD=0.07), and low heterogeneity (I2=22%) and a 95% CI that crossed zero (95% CI: -0.09 to 0.24). The 5 independent trials were not significant in improving pain score (SMD = -0.02, 95% CI: -0.19 to 0.16). This review also revealed no significance in improving Lequesne index (SMD = -0.27, 95% CI: -0.72 to 0.19). The meta-analysis from the 2 independent trials was significant in improving femorotibial angle (SMD = -0.41, 95% CI: -0.73 to -0.09). In conclusion, this meta-analysis suggested that lateral wedge insoles can improve femorotibial angle but are of no benefit with pain and functions in knee osteoarthritis.

GABAA receptor subunit gene polymorphisms predict symptom-based and developmental deficits in Chinese Han children and adolescents with autistic spectrum disorders.

GABAA receptor subunit genes GABRB3, GABRA5, and GABRG3 located on chromosome 15q11-q13 have been implicated in the etiology of autistic spectrum disorders (ASD). This study intended to investigate the possible role of single-nucleotide polymorphisms (SNPs) present in GABRB3 (rs2081648 and rs1426217), GABRA5 (rs35586628), and GABRG3 (rs208129) genes in ASD susceptibility and symptom-based and developmental phenotypes of ASD in Chinese Han children and adolescents. 99 ASD patients and 231 age- and gender- frequency-matched typical developing (TD) controls were tested by TaqMan® genotyping assay. Symptom-based phenotypes were evaluated by Childhood Autism Rating Scale (CARS) and Autism Behavior Checklist (ABC), and developmental phenotypes were assessed by Early Childhood Development Questionnaire (ECDQ) in ASD patients. Three haplotypes and global χ 2 test of all SNPs demonstrated significant associations between ASD and TD groups. Besides, GABRB3 rs2081648, GABRA5 rs35586628, and GABRG3 rs208129 polymorphisms were associated with symptom-based deficits in social interaction, sensorimotor and somatosensory coordination, visual response, imitation, activity level, language expression and adaptability. Developmental abnormalities in late emergences of social interaction and fine motor were detected in GABRB3 rs2081648 polymorphism. Overall results indicated that gene synergy may participate in ASD pathogenesis, and GABAA receptor gene polymorphisms can predict symptom-based and developmental deficits in ASD individuals.

Controlled ROS production by corannulene: the vehicle makes a difference.

Curved corannulene (Cor) can produce reactive oxygen species (ROS) in a controlled manner due to the large dipole moment. However, the poor aqueous solubility of Cor necessitates the employment of solubilization vehicles. This work revealed that PEGylation was less efficient than the cyclodextrin complexation regarding ROS production.

Serum Oxytocin Levels and an Oxytocin Receptor Gene Polymorphism (rs2254298) Indicate Social Deficits in Children and Adolescents with Autism Spectrum Disorders.

The neuropeptide oxytocin (OT) and its receptor (OXTR) have been predicted to be involved in the regulation of social functioning in autism spectrum disorders (ASD). Objective of the study was to investigate serum OT levels and the OXTR rs2254298 polymorphism in Chinese Han children and adolescents with ASD as well as to identify their social deficits relevant to the oxytocinergic system. We tested serum OT levels using ELISA in 55 ASD subjects and 110 typically developing (TD) controls as well as genotyped the OXTR rs2254298 polymorphism using PCR-RFLP in 100 ASD subjects and 232 TD controls. Autistic symptoms were assessed by the Autism Behavior Checklist (ABC) and the Childhood Autism Rating Scale (CARS). There were no significant associations between OXTR rs2254298 polymorphism and ASD, serum OT levels and age, as well as serum OT levels and intelligent quotient (IQ) in both ASD and TD groups. However, ASD subjects exhibited elevated serum OT levels compared to TD controls and positive correlations between serum OT levels and "adaptation to change score" in the CARS and CARS total scores. Moreover, in the ASD group, significant relationships were revealed between the single-nucleotide polymorphism (SNP) rs2254298 and serum OT levels, the category "stereotypes and object use" in the ABC and the category "adaptation to change" in the CARS. These findings indicated that individuals with ASD may exhibit a dysregulation in OT on the basis of changes in OXTR gene expression as well as environmentally induced alterations of the oxytocinergic system to determine their social deficits.

When self-assembly meets topology: an enhanced micelle stability.

The topology of hydrophobic moieties can affect the stability of self-assembled micelles. Curved corannulene and flat perylene were selected as model hydrophobic molecules with poly(ethylene glycol) as the hydrophilic segment. The curvature can enhance the intermolecular π-π interaction, and hence the driving force of micelle formation.

Development Pattern on Lymph Node Resection in Minimally Invasive Esophagectomy and 2-year Survival Analysis.

Background Thoracoscopic-laparoscopic procedures have been used more in the operations of esophagus cancer; in most times we call it minimally invasive esophagectomy, which is becoming mature. However, the efficacy of minimally invasive esophagectomy is still unclear, especially about the dissection of lymph nodes and survival. Methods A retrospective review was performed. The development process of minimally invasive esophagectomy for esophageal cancer was divided into three stages: the first stage 20, the second stage 37, the third stage 50. Result Total 107 patients underwent minimally invasive esophagectomy between July 2010 and May 2015. The number of lymph node resected during the three stages increased significantly, with a mean of 12.65, 15.91, and 20.16 nodes, respectively (p = 0.0075). The number of lymph nodes dissection greater than or equal to 12 or 18 increased significantly (p = 0.000). The patients from the first and the second stages had the similar 2-year survival rate (p = 0.8618). There is no significant difference in the 2-year disease-free survival rate (p = 0.606). Conclusion Surgeons accumulate experience on lymphadenectomy during minimally invasive esophagectomy as time goes by, and experience on 50 to 60 cases is essential and necessary to accomplish an apparent progress.

Triptolide reverses the Taxol resistance of lung adenocarcinoma by inhibiting the NF-κB signaling pathway and the expression of NF-κB-regulated drug-resistant genes.

Paclitaxel (or Taxol®) is a first-line chemotherapeutic drug for the treatment of non-small cell lung cancer; however, resistance to the drug is an important factor, which influences the outcome of chemotherapy. The present study aimed to investigate the role of triptolide (TPL) in reversing Taxol­resistant human lung adenocarcinoma and to elucidate the underlying molecular mechanism of resistance reversal mediated by TPL. It was hypothesized that this experimental approach would assist in solving the problem of chemotherapeutic resistance in non­small cell lung cancer, thereby improving the clinical outcomes. The human Taxol­resistant lung adenocarcinoma cell line, A549/Taxol, was established. The resistance index of the cell line was calculated, according to the half maximal inhibitory concentration (IC50) of A549/Taxol IC50 of A549, to be 51.87. The levels of apoptosis and the cell cycle in the A549/Taxol cell line were assessed to confirm the effects of TPL at three different concentrations (0.03, 0.3 and 3 µmol/l) and treatment durations (2, 4, 6 and 12 h) by flow cytometric analysis, and the inhibition of the NF­κB signaling pathway and the expression of NF­κB­regulated drug­resistant proteins were determined by immunofluorescence and western blotting, respectively. The administration of TPL promoted cell apoptosis in the A549/Taxol lung adenocarcinoma Taxol­resistant cell line and also promoted cell cycle regulation. The drug was also able to elicit a reversal of the drug resistance. TPL inhibited the nuclear factor­κB (NF­κB) signaling pathway and the expression of NF­κB­regulated drug­resistant genes, including those for FLICE­like inhibitory protein, X­linked inhibitor of apoptosis protein, Bcl­2, Bcl­xL and cyclo­oxygenase­2. TPL exerted a marked drug­resistance­reversal effect on human lung adenocarcinoma Taxol resistance, and the effect was revealed to be dose­ and time­dependent. In conclusion, TPL exerted its role in the process of resistance reversal by inhibiting the NF­κB signaling pathway, and the transcription and expression of NF-κB-regulated drug-resistant genes.

Highly-sensitive gas pressure sensor using twin-core fiber based in-line Mach-Zehnder interferometer.

A Mach-Zehnder interferometer based on a twin-core fiber was proposed and experimentally demonstrated for gas pressure measurements. The in-line Mach-Zehnder interferometer was fabricated by splicing a short section of twin-core fiber between two single mode fibers. A micro-channel was created to form an interferometer arm by use of a femtosecond laser to drill through one core of the twin-core fiber. The other core of the fiber was remained as the reference arm. Such a Mach-Zehnder interferometer exhibited a high gas pressure sensitivity of -9.6 nm/MPa and a low temperature cross-sensitivity of 4.4 KPa/°C. Moreover, ultra-compact device size and all-fiber configuration make it very suitable for highly-sensitive gas pressure sensing in harsh environments.

Spectrum sensing of trace C(2)H(2) detection in differential optical absorption spectroscopy technique.

An improved algorithm for trace C(2)H(2) detection is presented in this paper. The trace concentration is accurately calculated by focusing on the absorption spectrum from the frequency domain perspective. The advantage of the absorption spectroscopy frequency domain algorithm is its anti-interference capability. First, the influence of the background noise on the minimum detectable concentration is greatly reduced. Second, the time-consuming preprocess of spectra calibration in the differential optical absorption spectroscopy technique is skipped. Experimental results showed the detection limit of 50 ppm is achieved at a lightpath length of 0.2 m. This algorithm can be used in real-time spectrum analysis with high accuracy.

Ultrasensitive refractive index sensor based on a Mach-Zehnder interferometer created in twin-core fiber.

We proposed and experimentally demonstrated a twin-core fiber (TCF)-based Mach-Zehnder interferometer (MZI) to develop an ultrasensitive refractive index (RI) sensor. This fiber MZI was constructed by splicing a short section of TCF between two sections of single mode fibers. A microchannel was drilled through one core of the TCF by means of femtosecond laser micromachining to create one arm of the proposed interferometer, and the other core worked as the second arm. Such a fiber interferometer exhibits an ultrahigh RI sensitivity of -10981 nm/RIU and a low temperature cross-sensitivity of 3.96×10(-6) RIU/°C. Moreover, the ultra-compact device size and all-fiber configuration make it very suitable for highly sensitive RI sensing at precise location.