Identifying specific TLS-associated genes as potential biomarkers for predicting prognosis and evaluating the efficacy of immunotherapy in soft tissue sarcoma.

Background: The tertiary lymphatic structure (TLS) is an important component of the tumor immune microenvironment and has important significance in patient prognosis and response to immune therapy. However, the underlying mechanism of TLS in soft tissue sarcoma remains unclear. Methods: A total of 256 RNAseq and 7 single-cell sequencing samples were collected from TCGA-SARC and GSE212527 cohorts. Based on published TLS-related gene sets, four TLS scores were established by GSVA algorithm. The immune cell infiltration was calculated via TIMER2.0 and "MCPcounter" algorithms. In addition, the univariate, LASSO, and multivariate-Cox analyses were used to select TLS-related and prognosis-significant hub genes. Single-cell sequencing dataset, clinical immunohistochemical, and cell experiments were utilized to validate the hub genes. Results: In this study, four TLS-related scores were identified, and the total-gene TLS score more accurately reflected the infiltration level of TLS in STS. We further established two hub genes (DUSP9 and TNFSF14) prognosis markers and risk scores associated with soft tissue sarcoma prognosis and immune therapy response. Flow cytometry analysis showed that the amount of CD3, CD8, CD19, and CD11c positive immune cell infiltration in the tumor tissue dedifferentiated liposarcoma patients was significantly higher than that of liposarcoma patients. Cytological experiments showed that soft tissue sarcoma cell lines overexpressing TNFSF14 could inhibit the proliferation and migration of sarcoma cells. Conclusion: This study systematically explored the TLS and related genes from the perspectives of bioinformatics, clinical features and cytology experiments. The total-gene TLS score, risk score and TNFSF14 hub gene may be useful biomarkers for predicting the prognosis and immunotherapy efficacy of soft tissue sarcoma.

Randomized controlled trial for time-restricted eating in overweight and obese young adults.

Time-restricted eating (TRE) is known to improve metabolic health, whereas very few studies have compared the effects of early and late TRE (eTRE and lTRE) on metabolic health. Overweight and obese young adults were randomized to 6-h eTRE (eating from 7 a.m. to 1 p.m.) (n = 21), 6-h lTRE (eating from 12 p.m. to 6 p.m.) (n = 20), or a control group (ad libitum intake in a day) (n = 19). After 8 weeks, 6-h eTRE and lTRE produced comparable body weight loss compared with controls. Compared with control, 6-h eTRE reduced systolic blood pressure, mean glucose, fasting insulin, insulin resistance, leptin, and thyroid axis activity, whereas lTRE only reduced leptin. These findings shed light on the promise of 6-h eTRE and lTRE for weight loss. Larger studies are needed to assess the promise of eTRE to yield better thyroid axis modulation and overall cardiometabolic health improvement.

Construction of an HCC recurrence model basedon the investigation of immune-relatedlncRNAs and related mechanisms.

Long noncoding RNAs (lncRNAs) are emerging as critical regulators of gene expression and play fundamental roles in immune regulation. Growing evidence suggests that immune-related genes and lncRNAs can serve as markers to predict the prognosis of patients with cancers, including hepatocellular carcinoma (HCC). This study aimed to contract an immune-related lncRNA (IR-lncRNA) signature for prospective assessment to predict early recurrence of HCC. A total of 319 HCC samples under radical resection were randomly divided into a training cohort (161 samples) and a testing cohort (158 samples). In the training dataset, univariate, lasso, and multivariate Cox regression analyses identified a 9-IR-lncRNA signature closely related to disease-free survival. Kaplan-Meier analysis, principal component analysis, gene set enrichment analysis, and nomogram were used to evaluate the risk model. The results were further confirmed in the testing cohort. Furthermore, we constructed a competitive endogenous RNA regulatory network. The results of the present study indicated that this 9-IR-lncRNA signature has important clinical implications for improving predictive outcomes and guiding individualized treatment in HCC patients. These IR-lncRNAs and regulated genes may be potential biomarkers associated with the prognosis of HCC.

Sesamin attenuates PM2.5-induced cardiovascular injury by inhibiting ferroptosis in rats.

Objective: This study aimed to elucidate the pharmacological effects of sesamin (Ses) and its mechanism of action towards PM2.5-induced cardiovascular injuries. Method: Forty Sprague Dawley (SD) rats were randomly divided into five groups: a saline control group; a PM2.5 exposure group; and low-, middle-, and high-dose Ses pretreatment groups. The SD rats were pretreated with different concentrations of Ses for 21 days. Afterward, the rats were exposed to ambient PM2.5 by intratracheal instillation every other day for a total of three times. The levels of inflammatory markers, including tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1ß), and interleukin-6 (IL-6), and indicators related to oxidative responses, such as total superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA), were measured in the blood and heart. The expression of ferroptosis-related proteins in heart tissues was determined via western blot and immunohistochemistry. Results: Ses pretreatment substantially ameliorated cardiovascular injuries in rats as evidenced by the decrease in the pathological score and collagen area. The decreased levels of SOD, GSH, and GSH-Px in the heart and serum were inhibited by Ses. In addition, Ses not only notably increased the activity of antioxidant enzymes but also reduced the levels of MDA, CK, LDH, CK-MB, IL-6, TNF-α, IL-1ß, and IL-6. Furthermore, Ses pretreatment upregulated the expression levels of GPX4, SLC7A11, TFRC, and FPN1 and inhibited the expression levels of FTH1 and FTL. Conclusion: Ses pretreatment could ameliorate PM2.5-induced cardiovascular injuries perhaps by inhibiting ferroptosis. Therefore, Ses pretreatment may be a novel strategy for the prevention and treatment of PM2.5-induced cardiovascular injury.

Impact of Prior Ischemic Stroke on Outcomes in Patients With Heart Failure　- A Propensity-Matched Study.

BACKGROUND: Whether ischemic stroke per se, rather than older age or additional comorbidities, accounts for the adverse prognosis of heart failure (HF) is uncertain. The present study examineed the intrinsic association of ischemic stroke with outcomes in a propensity-matched cohort.Methods and Results:Of 1,351 patients hospitalized with HF, 388 (28.7%) had prior ischemic stroke. Using propensity score for prior ischemic stroke, estimated for each patient, a matched cohort of 379 pairs of HF patients with and without prior ischemic stroke, balanced on 32 baseline characteristics was assembled. At 30 days, prior ischemic stroke was associated with significantly higher risks of the combined endpoint of all-cause death or readmission (hazard ratio [HR]: 1.91; 95% confidence interval [CI]: 1.38 to 2.65; P<0.001), all-cause death (HR: 2.08; 95% CI: 1.28 to 3.38; P=0.003), all-cause readmission (HR: 2.67; 95% CI: 1.78 to 4.01; P<0.001), and HF readmission (HR: 2.11; 95% CI: 1.19 to 3.72; P=0.010). Prior ischemic stroke was associated with a significantly higher risk of all 4 outcomes at both 6 months and 1 year. CONCLUSIONS: Prior ischemic stroke was a potent and persistent risk predictor of death and readmission among patients with HF after accounting for clinical characteristics.

CRL4Cdt2 ubiquitin ligase regulates Dna2 and Rad16 (XPF) nucleases by targeting Pxd1 for degradation.

Structure-specific endonucleases (SSEs) play key roles in DNA replication, recombination, and repair. SSEs must be tightly regulated to ensure genome stability but their regulatory mechanisms remain incompletely understood. Here, we show that in the fission yeast Schizosaccharomyces pombe, the activities of two SSEs, Dna2 and Rad16 (ortholog of human XPF), are temporally controlled during the cell cycle by the CRL4Cdt2 ubiquitin ligase. CRL4Cdt2 targets Pxd1, an inhibitor of Dna2 and an activator of Rad16, for degradation in S phase. The ubiquitination and degradation of Pxd1 is dependent on CRL4Cdt2, PCNA, and a PCNA-binding degron motif on Pxd1. CRL4Cdt2-mediated Pxd1 degradation prevents Pxd1 from interfering with the normal S-phase functions of Dna2. Moreover, Pxd1 degradation leads to a reduction of Rad16 nuclease activity in S phase, and restrains Rad16-mediated single-strand annealing, a hazardous pathway of repairing double-strand breaks. These results demonstrate a new role of the CRL4Cdt2 ubiquitin ligase in genome stability maintenance and shed new light on how SSE activities are regulated during the cell cycle.

Age-specific differences in non-cardiac comorbidities among elderly patients hospitalized with heart failure: a special focus on young-old, old-old, and oldest-old.

BACKGROUND: Despite the growing epidemic of heart failure (HF), there is limited data available to systematically compare non-cardiac comorbidities in the young-old, old-old, and oldest-old patients hospitalized for HF. The precise differences will add valuable information for better management of HF in elderly patients. METHODS: A total of 1053 patients aged 65 years or older hospitalized with HF were included in this study. Patients were compared among three age groups: (1) young-old: 65 to 74 years, (2) old-old: 75 to 84 years, and (3) oldest-old: ≥85 years. Clinical details of presentation, comorbidities, and prescribed medications were recorded. RESULTS: The mean age was 76.7 years and 12.7% were 85 years or older. Most elderly patients with HF (97.5%) had at least one of the non-cardiac comorbidities. The patterns of common non-cardiac comorbidities were different between the young-old and oldest-old group. The three most common non-cardiac comorbidities were anemia (53.6%), hyperlipidemia (45.9%), and diabetes (42.4%) in the young-old group, while anemia (73.1%), infection (58.2%), and chronic kidney disease (44.0%) in the oldest-old group. Polypharmacy was observed in 93.0% elderly patients with HF. Additionally, 29.2% patients were diagnosed with infection, and 67.0% patients were prescribed antibiotics. However, 60.4% patients were diagnosed with anemia with only 8.9% of them receiving iron repletion. CONCLUSIONS: Non-cardiac comorbidities are nearly universal in three groups but obviously differ by age, and inappropriate medications are very common in elderly patients with HF. Further treatment strategies should be focused on providing optimal medications for age-specific non-cardiac conditions.

Systematic analysis reveals the prevalence and principles of bypassable gene essentiality.

Gene essentiality is a variable phenotypic trait, but to what extent and how essential genes can become dispensable for viability remain unclear. Here, we investigate 'bypass of essentiality (BOE)' - an underexplored type of digenic genetic interaction that renders essential genes dispensable. Through analyzing essential genes on one of the six chromosome arms of the fission yeast Schizosaccharomyces pombe, we find that, remarkably, as many as 27% of them can be converted to non-essential genes by BOE interactions. Using this dataset we identify three principles of essentiality bypass: bypassable essential genes tend to have lower importance, tend to exhibit differential essentiality between species, and tend to act with other bypassable genes. In addition, we delineate mechanisms underlying bypassable essentiality, including the previously unappreciated mechanism of dormant redundancy between paralogs. The new insights gained on bypassable essentiality deepen our understanding of genotype-phenotype relationships and will facilitate drug development related to essential genes.

Active transport of cytoophidia in Schizosaccharomyces pombe.

The metabolic enzyme cytidine triphosphate synthase has recently been found to form micrometer-sized filamentous structures termed cytoophidia, which are evolutionarily conserved across prokaryotes and eukaryotes. The cytoophidium represents a novel type of membraneless organelle and behaves dynamically inside the cell. The question of how cytoophidia transport is mediated, however, remains unanswered. For the first time, we detected in this study the active transport of cytoophidia, taking advantage of the fission yeast Schizosaccharomyces pombe as an excellent model for studying membraneless organelles. We demonstrated that actin filaments, not microtubules, are responsible for this transport. Furthermore, we determined that Myo52, a type of myosin V, is required for the active transport of cytoophidia. These results reveal the major players critical to the dynamics of cytoophidia and extend our understanding of intracellular transport of membraneless organelles.-Li, H., Ye, F., Ren, J.-Y., Wang, P.-Y., Du, L.-L., Liu, J.-L. Active transport of cytoophidia in Schizosaccharomyces pombe.

[Statins decreases expression of five inflammation-associated microRNAs in the plasma of patients with unstable angina].

OBJECTIVE: To explore the influence of treatment with HMG-CoA reductase inhibitors (statins) on the expression profile of microRNAs (miRNAs) in the plasma of patients with unstable angina (UA). METHODS: The Taqman low-density miRNA array (TLDA) and significance analysis of microarrays (SAM) were used to identify distinct miRNA expression profiles in the plasma of UA patients treated with long-term and regular statins (UA receiving statins, n=6) compared with UA patients who had not received statins therapy before (UA received no statins, n=6). These differentially expressed miRNAs discovered in the profiling were further validated by real-time PCR in another 20 controls with non-cardiac chest pain, 26 UA patients received no statins, and 19 UA patients received statins. RESULTS: By using TLDA and SAM, significantly decreased expression levels of 21 miRNAs were observed in the UA patients receiving statins compared with those who received no statins (fold change>3 and false discovery rate<0.0001%). The unsupervised hierarchical clustering based on miRNA expression clearly separated the UA patients receiving statins from those who received no statins. Consistent with the profiling data, the levels of 5 inflammation-associated miRNAs (miR-106b, miR-21, miR-25, miR-451, and miR-92a) were down regulated (P<0.05) in the UA patients receiving statins compared with those who received no statins. CONCLUSION: A group of inflammation-associated miRNAs, consisting of miR-106b, miR-21, miR-25, miR-451, and miR-92a, could be decreased by treatment with statins and may be used as a novel biomarker for effectiveness of statins therapy in patients with UA.

Angiotensin-(1-7): new perspectives in atherosclerosis treatment.

Angiotensin (Ang)-(1-7) is recognized as a new bioactive peptide in renin-angiotensin system (RAS). Ang-(1-7) is a counter-regulatory mediator of Ang-II which appears to be protective against cardiovascular disease. Recent studies have found that Ang-(1-7) played an important role in reducing smooth muscle cell proliferation and migration, improving endothelial function and regulating lipid metabolism, leading to inhibition of atherosclerotic lesions and increase of plaque stability. Although clinical application of Ang-(1-7) is restricted due to its pharmacokinetic properties, identification of stabilized compounds, including more stable analogues and specific delivery compounds, has enabled clinical application of Ang-(1-7). In this review, we discussed recent findings concerning the biological role of Ang-(1-7) and related mechanism during atherosclerosis development. In addition, we highlighted the perspective to develop therapeutic strategies using Ang-(1-7) to treat atherosclerosis.

Myocardial injury after surgery is a risk factor for weaning failure from mechanical ventilation in critical patients undergoing major abdominal surgery.

BACKGROUND: Myocardial injury after noncardiac surgery (MINS) is a newly proposed concept that is common among adults undergoing noncardiac surgery and associated with substantial mortality. We analyzed whether MINS was a risk factor for weaning failure in critical patients who underwent major abdominal surgery. METHODS: This retrospective study was conducted in the Department of Critical Care Medicine of Peking University People's Hospital. The subjects were all critically ill patients who underwent major abdominal surgery between January 2011 and December 2013. Clinical and laboratory parameters during the perioperative period were investigated. Backward stepwise regression analysis was performed to evaluate MINS relative to the rate of weaning failure. Age, hypertension, chronic renal disease, left ventricular ejection fraction before surgery, Acute Physiologic and Chronic Health Evaluation II score, pleural effusion, pneumonia, acute kidney injury, duration of mechanical ventilation before weaning and the level of albumin after surgery were treated as independent variables. RESULTS: This study included 381 patients, of whom 274 were successfully weaned. MINS was observed in 42.0% of the patients. The MINS incidence was significantly higher in patients who failed to be weaned compared to patients who were successfully weaned (56.1% versus 36.5%; P<0.001). Independent predictive factors of weaning failure were MINS, age, lower left ventricular ejection fraction before surgery and lower serum albumin level after surgery. The MINS odds ratio was 4.098 (95% confidence interval, 1.07 to 15.6; P = 0.04). The patients who were successfully weaned had shorter hospital stay lengths and a higher survival rate than those who failed to be weaned. CONCLUSION: MINS is a risk factor for weaning failure from mechanical ventilation in critical patients who have undergone major abdominal surgery, independent of age, lower left ventricular ejection fraction before surgery and lower serum albumin levels after surgery.

Fission yeast Pxd1 promotes proper DNA repair by activating Rad16XPF and inhibiting Dna2.

Structure-specific nucleases play crucial roles in many DNA repair pathways. They must be precisely controlled to ensure optimal repair outcomes; however, mechanisms of their regulation are not fully understood. Here, we report a fission yeast protein, Pxd1, that binds to and regulates two structure-specific nucleases: Rad16XPF-Swi10ERCC1 and Dna2-Cdc24. Strikingly, Pxd1 influences the activities of these two nucleases in opposite ways: It activates the 3' endonuclease activity of Rad16-Swi10 but inhibits the RPA-mediated activation of the 5' endonuclease activity of Dna2. Pxd1 is required for Rad16-Swi10 to function in single-strand annealing, mating-type switching, and the removal of Top1-DNA adducts. Meanwhile, Pxd1 attenuates DNA end resection mediated by the Rqh1-Dna2 pathway. Disabling the Dna2-inhibitory activity of Pxd1 results in enhanced use of a break-distal repeat sequence in single-strand annealing and a greater loss of genetic information. We propose that Pxd1 promotes proper DNA repair by differentially regulating two structure-specific nucleases.

Twenty-year trends in major cardiovascular risk factors in hospitalized patients with acute myocardial infarction in Beijing.

BACKGROUND: Hypertension, diabetes mellitus, hypercholesterolaemia and current smoking are the strongest modifiable cardiovascular risk factors for acute myocardial infarction (AMI). We examined their changing trends over the last 20 years. METHODS: The clinical data of 3498 patients hospitalized in Peking University People's Hospital with AMI from 1991 to 2010 were used. Information was collected regarding to patients' demographic data, cardiovascular risk factors (hypertension, diabetes mellitus, hypercholesterolemia and current smoking). To assess trends over time in the prevalence of risk factors, we categorized patients into four groups (1991 to 1995, 1996 to 2000, 2001 to 2005 and 2006 to 2010). RESULTS: Highly significant increases were observed in the prevalence of hypertension from 40.8% to 55.6% for males and from 58.0% to 69.0% for females; and diabetes mellitus from 12.9% to 30.8% for males and from 23.0% to 42.3% for females. Similarly, the prevalence of hypercholesterolaemia decreased from 53.1% to 30.7% for males and from 57.0% to 44.0% for females. The prevalence of current smoking decreased in females from 29.0% to 11.1%, but remained unchanged in males. In addition, the proportion of patients with more than three modifiable risk factors increased from 19.0% to 27.1% and the age at onset of AMI extended to younger as well as older individuals. CONCLUSIONS: The prevalence of hypertension and diabetes mellitus are still increasing in patients with AMI in Beijing and although the prevalence of hypercholesterolaemia and current smoking decreased, high clustering of risk factors were commonly present. These adverse trends show a compelling need for more effective management of cardiovascular risk factors.

Phosphorylation-dependent assembly and coordination of the DNA damage checkpoint apparatus by Rad4(TopBP1).

The BRCT-domain protein Rad4(TopBP1) facilitates activation of the DNA damage checkpoint in Schizosaccharomyces pombe by physically coupling the Rad9-Rad1-Hus1 clamp, the Rad3(ATR) -Rad26(ATRIP) kinase complex, and the Crb2(53BP1) mediator. We have now determined crystal structures of the BRCT repeats of Rad4(TopBP1), revealing a distinctive domain architecture, and characterized their phosphorylation-dependent interactions with Rad9 and Crb2(53BP1). We identify a cluster of phosphorylation sites in the N-terminal region of Crb2(53BP1) that mediate interaction with Rad4(TopBP1) and reveal a hierarchical phosphorylation mechanism in which phosphorylation of Crb2(53BP1) residues Thr215 and Thr235 promotes phosphorylation of the noncanonical Thr187 site by scaffolding cyclin-dependent kinase (CDK) recruitment. Finally, we show that the simultaneous interaction of a single Rad4(TopBP1) molecule with both Thr187 phosphorylation sites in a Crb2(53BP1) dimer is essential for establishing the DNA damage checkpoint.

A proteome-wide visual screen identifies fission yeast proteins localizing to DNA double-strand breaks.

DNA double-strand breaks (DSBs) are a major threat to genome integrity. Proteins involved in DNA damage checkpoint signaling and DSB repair often relocalize and concentrate at DSBs. Here, we used an ORFeome library of the fission yeast Schizosaccharomyces pombe to systematically identify proteins targeted to DSBs. We found 51 proteins that, when expressed from a strong exogenous promoter on the ORFeome plasmids, were able to form a distinct nuclear focus at an HO endonuclease-induced DSB. The majority of these proteins have known connections to DNA damage response, but few have been visualized at a specific DSB before. Among the screen hits, 37 can be detected at DSBs when expressed from native promoters. We classified them according to the focus emergence timing of the endogenously tagged proteins. Eight of these 37 proteins are yet unnamed. We named these eight proteins DNA-break-localizing proteins (Dbls) and performed preliminary functional analysis on two of them, Dbl1 (SPCC2H8.05c) and Dbl2 (SPCC553.01c). We found that Dbl1 and Dbl2 contribute to the normal DSB targeting of checkpoint protein Rad26 (homolog of human ATRIP) and DNA repair helicase Fml1 (homolog of human FANCM), respectively. As the first proteome-wide inventory of DSB-localizing proteins, our screen result will be a useful resource for understanding the mechanisms of eukaryotic DSB response.

[A meta-analysis on the safety of combination therapy with fenofibrate and statins].

OBJECTIVE: The aim of this study was to assess the safety of fenofibrate-statin combination therapy. METHODS: Medline, Cochrane Library, Web of Knowledge and CNKI were searched for 2184 randomized controlled trials. Finally, twenty-six studies with a total of 9494 participants were included in this analysis. RESULTS: Compared with statins group, the fenofibrate-statin group had significantly higher incidence of aminotransferase elevations (OR 1.67, 95%CI 1.22-2.30, P < 0.05) . The two groups had identical incidence of creatin kinase elevations (OR 0.86, 95%CI 0.62-1.20, P > 0.05) , muscle-associated adverse events (OR 0.98, 95%CI 0.88-1.09, P > 0.05) and withdrawals due to hepatotoxicity or muscle toxicity. The safety of fenofibrate + standard-dose statin regimens were similar to those in fenofibrate-statin group. CONCLUSION: Combined fenofibrate-statin treatment is generally safe and well tolerated, liver function should be monitored before and during and after therapy.

High density lipoprotein suppresses lipoprotein associated phospholipase A2 in human monocytes-derived macrophages through peroxisome proliferator-activated receptor-γ pathway.

BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is mainly secreted by macrophages, serving as a specific marker of atherosclerotic plaque and exerting pro-atherogenic effects. It is known that high-density lipoprotein (HDL) plays an important role against atherosclerosis by inhibiting pro-inflammatory factors, however, the relationship between HDL and Lp-PLA2 remains elusive. METHODS: In this study, reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and a platelet-activating factor (PAF) acetylhydrolase assay were performed to determine the Lp-PLA2 mRNA level, protein expression and activity in human monocyte-derived macrophages upon HDL treatment of different concentrations and durations. To investigate the underlying mechanism of HDL-induced Lp-PLA2 action, pioglitazone, a peroxisome proliferator-activated receptor-γ (PPARγ) ligand, was introduced to human monocyte-derived macrophages and mRNA and protein levels of Lp-PLA2, as well as its activity, were determined. RESULTS: Lp-PLA2 mRNA levels, protein expression and activity were significantly inhibited in response to HDL treatment in a dose and time dependent manner in human monocyte-derived macrophages. Pioglitazone treatment (1 - 10 ng/ml) upregulated the Lp-PLA2 mRNA level, protein expression and activity in human monocyte-derived macrophages, while the effects were markedly reversed by HDL. In addition, pioglitazone resulted in a significant increase in PPARγ phosphorylation in human monocyte-derived macrophages, which could be inhibited by HDL. CONCLUSION: These findings indicate that HDL suppresses the expression and activity of Lp-PLA2 in human monocyte-derived macrophages, and the underlying mechanisms may be mediated through the PPARγ pathway.

[Application of next generation sequencing in microRNA detection].

MicroRNAs (miRNAs) are a class of ~22nt long non-coding RNAs. They are evolutionarily conserved and play essential roles in the regulation of post-transcriptional gene expression. The rapidly developing next generation sequencing (NGS) has important applications in miRNA detection. This review is focused on the mechanism of three NGS platforms and their applications in miRNA detection. In contrast to traditional methods, NGS has major advantages: high throughput, precise, accurate, and repeatable. Its application includes new miRNAs exploration, detection of miRNA*, miRNA editing, and isomiR and target mRNA detection. As NGS develops, the cost of sequencing is declining which makes it possible for NGS to be widely used in the coming years. Next generation sequencing will greatly promote researches of miRNAs.

Elevated plasma lipoprotein-associated phospholipase A2 activity is associated with plaque rupture in patients with coronary artery disease.

BACKGROUND: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) has recently been shown to be positively related to coronary events in patients with coronary artery disease (CAD). However, direct evidence about the relationship between circulation Lp-PLA(2) activity and vulnerable plaque in patients with CAD remains lacking. METHODS: Plasma Lp-PLA(2) activity was determined in 146 consecutive patients with CAD who underwent clinically-indicated coronary angiography and preinterventional intravascular ultrasound (IVUS). RESULTS: Eighty-three patients were included in the final analysis after the initial screening. Sixty (72.3%) were acute coronary syndrome (ACS) patients and 23 (27.7%) were stable angina pectoris (SAP) patients. Plaque rupture occurred in 39 (47.0%) patients, and 34 (87.2%) were from ACS patients and 5 (12.8%) from SAP patients. There were no significant differences in clinical and angiographic characteristics between patients with plaque rupture and those without plaque rupture, except for smoking, high-sensitive C-reactive protein (hs-CRP) level and Lp-PLA(2) activity (all P < 0.05). IVUS measurement uncovered that patients with plaque rupture had more frequent positive remodeling (74.4% vs. 43.2%, P = 0.004), soft plaques (64.1% vs. 36.4%, P = 0.012) and higher remodeling index (1.13 ± 0.16 vs. 0.99 ± 0.11, P = 0.041) as compared with those without plaque rupture. Multivariate Logistic regression analysis showed that plasma Lp-PLA(2) activity was independently associated with plaque rupture after adjusting for smoking, positive remodeling and soft plaque (Model 1: odds ratio (OR) 1.13, 95% confidence interval (CI): 1.06 - 1.20) or adjusting for smoking, hs-CRP level, positive remodeling and soft plaque (Model 2: OR 1.11, 95%CI: 1.04 - 1.19). CONCLUSIONS: Plasma Lp-PLA(2) activity is associated with plaque rupture in patients with CAD, independently of traditional CAD risk factors, hs-CRP level and IVUS parameters. Lp-PLA(2) may be a risk marker for vulnerable plaques.