The Associations of Platelet Activation and Coagulation Parameters with Obstructive Sleep Apnoea: A Large-Scale Observational Study.

Objectives: Obstructive sleep apnoea (OSA) is associated with an increased risk of cardiovascular disease, with alterations in coagulability suspected as the mediating factor. This study explored blood coagulability and breathing-related parameters during sleep in patients with OSA. Design: Cross-sectional observational study. Setting. Shanghai Sixth People's Hospital. Participants. 903 patients diagnosed by standard polysomnography. Main Outcome and Measures. The relationships between coagulation markers and OSA were evaluated using Pearson's correlation, binary logistic regression, and restricted cubic spline (RCS) analyses. Results: The platelet distribution width (PDW) and activated partial thromboplastin time (APTT) decreased significantly with increasing OSA severity (both p < 0.001). PDW was positively associated with the apnoea-hypopnea index (AHI), oxygen desaturation index (ODI), and microarousal index (MAI) (ß = 0.136, p < 0.001; ß = 0.155, p < 0.001; and ß = 0.091, p = 0.008, respectively). APTT was negatively correlated with AHI (ß = -0.128, p < 0.001) and ODI (ß = -0.123, p = 0.001). PDW was negatively correlated with percentage of sleep time with oxygen saturation below 90%(CT90) (ß = -0.092, p = 0.009). The minimum arterial oxygen saturation (SaO2) correlated with PDW (ß = -0.098, p = 0.004), APTT (ß = 0.088, p = 0.013), and prothrombin time (PT) (ß = 0.106, p = 0.0003). ODI was risk factors for PDW abnormalities (odds ratio (OR) = 1.009, p = 0.009) after model adjustment. In the RCS, a nonlinear dose-effect relationship was demonstrated between OSA and the risk of PDW and APTT abnormalities. Conclusion: Our study revealed nonlinear relationships between PDW and APTT, and AHI and ODI, in OSA, with AHI and ODI increasing the risk of an abnormal PDW and thus also the cardiovascular risk. This trial is registered with ChiCTR1900025714.

MicroRNA-301b and its target gene synaptosome-associated protein 91 as important modulators in esophageal cancer: functional experiments.

The aim of this study was to probe the influence of microRNA-301b (miR-301b) in esophageal cancer pathogenesis. Based on the data acquired from The Cancer Genome Atlas database, we found that miR-301b was highly expressed in esophageal cancer tissues and high expression of miR-301b was related to worse prognosis in patients with esophageal cancer. Quantitative real-time PCR revealed that the expression of miR-301b was higher in all examined esophageal cancer cell lines (ECA109, KY-SE150, TE-1, and NEC) than that in a human esophageal epithelial cell line (HEEC). Upregulation/downregulation of miR-301b facilitated/suppressed the growth, migration, and invasion of ECA109/KY-SE150 cells. Synaptosome-associated protein 91 (SNAP91) was proved to be one of the target genes of miR-301b and was negatively modulated by miR-301b. Besides, SNAP91 was lowly expressed in human esophageal cancer tissues and cell lines. Meanwhile, low expression of SNAP91 was concerned with poor prognosis in patients with esophageal cancer. Furthermore, we discovered that overexpression/depletion of SNAP91 suppressed/facilitated the proliferation of KY-SE150/ECA109 cells. MiR-301b and SNAP91 had little impact on HEEC cell proliferation and this degree of influence was negligible compared with their impacts on esophageal cancer cell proliferation. By rescue assay, we showed that overexpression of SNAP91 restrained the growth, migration, and invasion of ECA109 cells with overexpressed miR-301b while knockdown of SNAP91 showed the contrary effects on KY-SE150 cells with downregulated miR-301b. These consequences indicated that miR-301b played an important effect on esophageal cancer cells through regulating SNAP91, insinuating that miR-301b/SNAP91 might be novel potential targets for esophageal cancer therapy and prognosis.

Complications and local recurrence of malignant liver tumor after ablation in risk areas: a retrospective analysis.

INTRODUCTION: Microwave ablation (MWA) is an effective local treatment for malignant liver tumors; however, its efficacy and safety for liver tumors adjacent to important organs are debatable. PATIENTS AND METHODS: Forty-three cases with liver tumors adjacent to important organs were the risk group and 66 cases were the control group. The complications between two groups were compared by chi-square test and t-test. Local tumor recurrence (LTR) was analyzed by log-rank test. Factors affecting complications were analyzed by logistic regression and Spearman analyses. Factors affecting LTR were analyzed by Cox regression analysis. A receiver operating characteristic curve predicted pain treated with drugs and LTR. RESULTS: We found no significant difference in complications and LTR between two groups. The risk group experienced lower ablation energy and more antennas per tumor than control group. Necrosis volume after MWA was positively correlated with pain; necrosis volume and ablation time were positively correlated with recovery duration. Major diameter of tumor >3 cm increased risk of LTR by 3.319-fold, good lipiodol deposition decreased risk of LTR by 73.4%. The area under the curve (AUC) for necrosis volume in predicting pain was 0.74, with a 69.1 cm3 cutoff. AUC for major diameter of tumor in predicting LTR was 0.68, with a 27.02 mm cutoff. CONCLUSION: MWA on liver tumors in at-risk areas is safe and effective, this is largely affected by proper ablation energy, antennas per tumor, and experienced doctors. LTR is primarily determined by major diameter of tumor and lipiodol deposition status.

A Network Pharmacology Based Research on the Mechanism of Donepezil in Treating Alzheimer's Disease.

Objective: In order to explore and further understand the efficacy of donepezil (DNP) in the treatment of Alzheimer's disease (AD), this research was conducted based on network pharmacology and molecular docking. Method: Compounds of DNP and its effective targets were collected using the TCMSP Chinese medicine system pharmacology database. Disease targets were screened and selected utilizing GeneCards, TTD, DrugBank, CTD, and other online databases. Then, Venn diagrams were generated to identify the intersections. A diseases-drug-active ingredient-key target protein interaction (PPI) network was constructed using the STING database. GO and KEGG enrichment analyses were conducted to predict the function and mechanism of DNP, which were visualized by graphs and bubble charts. After the screening, the top five interacting targets in the PPI network and the compound containing the most active target were selected for molecular docking. Results: The study received 110 potential targeting genes and 155 signaling pathways. A strong association between DNP and modulation of chemical synaptic transmission and the regulation of trans-synaptic signaling is noted. Signaling pathways related to the proliferation, differentiation, and survival of cells are also found positively relative. The results revealed that the mechanism of its therapeutic effect is multi-component, multi-target, and multi-pathway, laying a foundation for the follow-up in-depth study of the mechanism of DNP in the treatment of AD. Conclusion: This research provides a superior prediction that AD could be treated using DNP which targets the key proteins and essential pathways associated with the recovery of AD.

Clinical Effect of Butylphthalide Combined with Rt-PA Intravenous Thrombolysis in the Treatment of Acute Cerebral Infarction.

Objective: To assess the clinical effect of butylphthalide combined with rt-PA intravenous thrombolysis in the treatment of acute cerebral infarction (ACI). Methods: Totally, 312 acute cerebral infarction patients were included in this research. Those in the group for experiment received butylphthalide (25 mg QD) combined with rt-PA intravenous thrombolysis (0.9 mg/kg QD), while the control group received rt-PA intravenous (P < 0.05). Moreover, NIHSS (NIH Stroke Scale/Score) and Barthel index scores in the two groups improved, NIHSS score had ameliorated, and Barthel index score was higher than that in the reference group (P < 0.05). Conclusion: The combination of butylphthalide and recombination plasminogen activator alteplase (rt-PA) intravenous thrombolysis has a significant clinical effect in the treatment of acute cerebral infarction. It can alleviate the inflammatory symptoms, accelerate the recovery of neurological function, and improve the ability of daily living.

Comprehensive Analysis of N6-Methyladenosine Regulators in the Subcluster Classification and Drug Candidates Prediction of Severe Obstructive Sleep Apnea.

Background: Obstructive sleep apnea (OSA) is the most common type of sleep apnea that impacts the development or progression of many other disorders. Abnormal expression of N6-methyladenosine (m6A) RNA modification regulators have been found relating to a variety of human diseases. However, it is not yet known if m6A regulators are involved in the occurrence and development of OSA. Herein, we aim to explore the impact of m6A modification in severe OSA. Methods: We detected the differentially expressed m6A regulators in severe OSA microarray dataset GSE135917. The least absolute shrinkage and selection operator (LASSO) and support vector machines (SVM) were used to identify the severe OSA-related m6A regulators. Receiver operating characteristic (ROC) curves were performed to screen and verify the diagnostic markers. Consensus clustering algorithm was used to identify m6A patterns. And then, we explored the character of immune microenvironment, molecular functionals, protein-protein interaction networks and miRNA-TF coregulatory networks for each subcluster. Finally, the Connectivity Map (CMap) tools were used to tailor customized treatment strategies for different severe OSA subclusters. An independent dataset GSE38792 was used for validation. Results: We found that HNRNPA2B1, KIAA1429, ALKBH5, YTHDF2, FMR1, IGF2BP1 and IGF2BP3 were dysregulated in severe OSA patients. Among them, IGF2BP3 has a high diagnostic value in both independent datasets. Furthermore, severe OSA patients can be accurately classified into three m6A patterns (subcluster1, subcluster2, subcluster3). The immune response in subcluster3 was more active because it has high M0 Macrophages and M2 Macrophages infiltration and up-regulated human leukocyte antigens (HLAs) expression. Functional analysis showed that representative genes for each subcluster in severe OSA were assigned to histone methyltransferase, ATP synthesis coupled electron transport, virus replication, RNA catabolic, multiple neurodegeneration diseases pathway, et al. Moreover, our finding demonstrated cyclooxygenase inhibitors, several of adrenergic receptor antagonists and histamine receptor antagonists might have a therapeutic effect on severe OSA. Conclusion: Our study presents an overview of the expression pattern and crucial role of m6A regulators in severe OSA, which may provide critical insights for future research and help guide appropriate prevention and treatment options.

The Associations Between Sleep Architecture and Metabolic Parameters in Patients With Obstructive Sleep Apnea: A Hospital-Based Cohort Study.

Background and Objectives: The associations between objective sleep architecture and metabolic parameters have been rarely studied in patients with obstructive sleep apnea (OSA). Here, we evaluated the associations between objective sleep measures derived via polysomnography (PSG) and metabolic parameters. Methods: A total of 2,308 subjects with suspected OSA were included. We measured common metabolic parameters such as body mass index (BMI) and glucose, insulin, blood pressure, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels. All subjects underwent full-night PSG. PSG sleep parameters included total sleep time (TST), time spent in slow-wave sleep (SWS) and rapid eye movement (REM) sleep, sleep efficiency, and the microarousal index (MAI). Results: The TST correlated with the BMI, glucose level, and systolic blood pressure. The SWS/TST ratio correlated with BMI and glucose, TC, and TG levels. The REM/TST ratio correlated with BMI, glucose, insulin, and TG levels, and diastolic blood pressure. We found significant relationships between sleep efficiency and BMI, glucose levels, and TG levels. The MAI was significantly correlated with all metabolic parameters. After adjustment for age, gender, smoking status, alcohol use, apnea hypopnea index, and oxygen desaturation index (ODI), multiple linear regression analysis showed that the MAI was independently associated with glucose level, TC, HDL, and LDL. REM/TST ratio was positively associated with diastolic blood pressure but negatively associated with glucose metabolism. Conclusions: Though some independent correlation between sleep and metabolic parameters was confirmed, only weak associations were observed, suggesting a clinically negligible influence of sleep structure. Further prospective studies are warranted to confirm our findings.

SERPINE1 as a cancer-promoting gene in gastric adenocarcinoma: facilitates tumour cell proliferation, migration, and invasion by regulating EMT.

We assessed the expression of Serpin Family E Member 1 (SERPINE1) and its prognostic values in gastric adenocarcinoma (GAC) by using the data from TCGA database. The biological functions of SERPINE1 in GAC cells were detected by cell counting Kit-8, colony-forming, Transwell, and wound-healing assays, appropriately. Relative mRNA and protein levels were detected by RT-qPCR and western blot. Bioinformatics analysis indicated that SERPINE1 was significantly up-regulated in GAC tissues compared to normal tissues. High SERPINE1 expression led to a short overall survival and could act as an independent prognosticator for GAC patients. Besides, down-regulation of SERPINE1 showed a suppressive effect on the phenotype of GAC cells and significantly inhibited the EMT process. Over-expression of SERPINE1 got the reverse outcomes. These data suggest that SERPINE1 contributes to the proliferation, invasion and migration of GAC cells, insinuating that SERPINE1 may be considered as a novel biomarker for GAC treatment.

Iodine-125 radioactive seed tissue implantation as a remedy treatment for recurrent cervical cancer.

PURPOSE: This study was designed to discuss feasibility, short-term efficacy, and complications of iodine-125 radioactive seed tissue implantation for remedying recurrent cervical cancer. MATERIALS AND METHODS: From June 2009 to December 2010, 17 patients with recurrent cervical cancer received radioactive seed implantation under computed tomography (CT) guidance. Matched peripheral dose was 145 Gy, while the number of implanted seeds was from 6 to 68 with a median of 20. Efficacy was determined based on the results of CT and 18 F-fluorodeoxyglucose positron emission tomography/CT. RESULTS: Postoperative follow-ups were from 4 to 18 months with a median follow-up time of 9.5 months. Nine patients died during follow-up while remaining patients survived during the follow-up period. Evaluation of efficacy: six patients had a complete response, four patients had a partial response, and seven patients had progressive disease, clinical efficacy rate as 58% (10/17). No patients had complications of radiation injury. Rate of 6 months and 1-year survival period was 74.8% and 18.3%, respectively. Comparing to patients who responded ineffectively to radioactive seed implantation, patients who responded effectively to radioactive seed implantation had a longer survival period (median 7.2 vs. median 10.4), in which the difference was statistically significant (P = 0.038). CONCLUSION: Iodine-125 radioactive seed tissue implantation is a feasible, effective, and safe treatment method for remedying or palliative treatment of recurrent cervical cancer. Patients who have recurrent cervical cancer and responded effectively to radioactive seed implantation will have a longer survival period.

The Association Between Genetic Polymorphism rs703842 in CYP27B1 and Multiple Sclerosis: A Meta-Analysis.

Multiple sclerosis (MS) is the most frequent nontraumatic disabling neurological disease among young adults. Previous studies have examined the association of rs703842 in CYP27B1 with MS susceptibility, with inconsistent results reported.The objective of this study is to conduct a systematic literature search and perform meta-analyses to examine whether rs703842 is associated with MS risk.We searched potential literature in PubMed, Cochrane Library, Embase, Google Scholar, Web of Science, and HuGE by using the following inclusion criteria: studies were on human subjects; the studies were case-control studies; studies included subjects who had MS and those who did not have MS; and the studies provided genotype data for rs703842 for subjects who had and did not have MS, or provided odds ratios (ORs) and the 95% confidence intervals (CIs) for assessing the association of rs703842 with MS, or provided sufficient data for the calculation of OR and the 95% CI. We used random-effects models to calculate the OR as a measure of association. We used I to assess between-study heterogeneity, and a funnel plot and Egger test to assess publication bias.Seven studies published since 2008 met the eligibility criteria and were included in the meta-analyses. We found that the C allele was significantly associated with reduced MS susceptibility (OR = 0.88, 95% CI: 0.80-0.89; P < 0.0001). We also found significant association of rs703842 with MS risk using a dominant and a recessive model (both P < 0.0002). Our results remain unchanged if our meta-analysis was limited to studies that included only Caucasian participants (OR = 0.85, 95% CI: 0.80-0.90; P < 0.0001).Our study has several limitations: The sample size is limited; We were unable to control for some important confounding factors as data for individual participant were not available; and Most of the included studies focus on MS risk in Caucasian. As a result, we could not perform meta-analysis for assessing the relationship in other ethnic groups.In summary, we found that the genetic variant rs703842 in CYP27B1 is associated with MS risk in Caucasians. More studies with larger sample size that control for important confounding factors are needed to validate the findings from this study.