Knockdown of long non-coding RNA PEG10 inhibits growth, migration and invasion of gastric carcinoma cells via up-regulating miR-3200.

Gastric cancer is the main leading cause of cancer-related death worldwide. The aberrant expression of paternally expressed gene 10 (PEG10) is involved in development of a range of cancers. However, the potential biological function and the underling mechanism of PEG10 in human gastric carcinoma are still unknown. Knocking down LncRNA PEG10 might represent a promising therapeutic strategy for the treatment of gastric cancer. The expression of PEG10, miR-3200, and AEG1 in human gastric carcinoma NCI-N87 cells were altered by cell transfection assay. Cell viability, migration, invasion, and apoptosis were determined by trypan blue exclusion, Transwell assay, and flow cytometric analysis, respectively. RNA and protein expression level of gene was analyzed by real-time PCR and Western blot. Luciferase reporter assay was conducted to determine the target gene of miR-3200. JNK and Wnt signal pathway protein expressions were tested by Western blot. The up-regulation of PEG10 was found in clinical samples. PEG10 knockdown effectively inhibited gastric carcinoma cell viability, migration, and invasion, but promoted cell apoptosis. This tumor-suppressing effect of PEG10 knockdown might be realized by up-regulating miR-3200 in vitro and in vivo. AEG1 was a direct target gene of miR-3200. Moreover, miR-3200 might suppress NCI-N87 cells by negative regulating AEG1. Up-regulating miR-3200 effectively blocked JNK and Wnt pathways likely via down-regulating AEG1. PEG10 knockdown played a carcinostatic role via up-regulating miR-3200 and further regulating AEG1 in gastric carcinoma cells, during which process, JNK pathway and Wnt pathway were blocked.

Dynamics of low-intermediate-high-confinement transitions in toroidal plasmas.

The dynamic features of the low-intermediate-high-(L-I-H) confinement transitions on HL-2A tokamak are presented. Here we report the discovery of two types of limit cycles (dubbed type-Y and type-J), which show opposite temporal ordering between the radial electric field and turbulence intensity. In type-Y, which appears first after an L-I transition, the turbulence grows first, followed by the localized electric field. In contrast, the electric field leads type-J. The turbulence-induced zonal flow and pressure-gradient-induced drift play essential roles in the two types of limit cycles, respectively. The condition of transition between types-Y and -J is studied in terms of the normalized radial electric field. An I-H transition is demonstrated to occur only from type-J.

[Epidemiological characteristics of a 2019-nCoV outbreak caused by Omicron variant BF.7 in Shenzhen].

Objective: To explore the epidemiological characteristic of a COVID-19 outbreak caused by 2019-nCoV Omicron variant BF.7 and other provinces imported in Shenzhen and analyze transmission chains and characteristics. Methods: Field epidemiological survey was conducted to identify the transmission chain, analyze the generation relationship among the cases. The 2019-nCoV nucleic acid positive samples were used for gene sequencing. Results: From 8 to 23 October, 2022, a total of 196 cases of COVID-19 were reported in Shenzhen, all the cases had epidemiological links. In the cases, 100 were men and 96 were women, with a median of age, M (Q1, Q3) was 33(25, 46) years. The outbreak was caused by traverlers initial cases infected with 2019-nCoV who returned to Shenzhen after traveling outside of Guangdong Province.There were four transmission chains, including the transmission in place of residence and neighbourhood, affecting 8 persons, transmission in social activity in the evening on 7 October, affecting 65 persons, transmission in work place on 8 October, affecting 48 persons, and transmission in a building near the work place, affecting 74 persons. The median of the incubation period of the infection, M (Q1, Q3) was 1.44 (1.11, 2.17) days. The incubation period of indoor exposure less than that of the outdoor exposure, M (Q1, Q3) was 1.38 (1.06, 1.84) and 1.95 (1.22, 2.99) days, respcetively (Wald χ2=10.27, P=0.001). With the increase of case generation, the number and probability of gene mutation increased. In the same transmission chain, the proportion of having 1-3 mutation sites was high in the cases in the first generation. Conclusions: The transmission chains were clear in this epidemic. The incubation period of Omicron variant BF.7 infection was shorter, the transmission speed was faster, and the gene mutation rate was higher. It is necessary to conduct prompt response and strict disease control when epidemic occurs.

A versatile control program for positioning and shooting targets in laser-plasma experiments.

We introduce a LabVIEW-based control program that significantly improves the efficiency and flexibility in positioning and shooting solid targets in laser-plasma experiments. The hardware driven by this program incorporates a target positioning subsystem and an imaging subsystem, which enables us to install up to 400 targets for one experimental campaign and precisely adjust them in six freedom degrees. The overall architecture and the working modes of the control program are demonstrated in detail. In addition, we characterized the distributions of target positions of every target holder and simultaneously saved the target images, resulting in a large dataset that can be used to train machine learning models and develop image recognition algorithms. This versatile control system has become an indispensable platform when preparing and conducting laser-plasma experiments.

Estimate of 2009 H1N1 influenza cases in Shenzhen--the biggest migratory city in China.

The 2009 novel H1N1 influenza pandemic had a significant impact on Shenzhen's population with 2063 laboratory-confirmed human H1N1 cases and five deaths being reported. We used parameters from two population-based surveys and the Shenzhen Influenza Surveillance System to estimate the total number of H1N1 influenza infections in Shenzhen in the 2009 pandemic. The attack rate of influenza-like illness (ILI) in family households was 11·2% (95% CI 9·4-13·0), with 80·2% (95% CI 77·8-82·5) seeking medical care. The ILI attack rate in workers was 38·1% (95% CI 34·3-41·7) with 72·5% (95% CI 66·9-78·0) seeking medical care. The average H1N1 positive rate in individuals reporting ILI and testing by polymerase chain reaction was 22·7%. A total of 611 000-768 000 people, or 4·7-5·9% of the Shenzhen population, are estimated to have experienced H1N1 influenza. The estimated total number of cases of H1N1 is likely to be 330 times greater than the number of laboratory-confirmed cases.

Five-channel tunable W-band Doppler backscattering system in the experimental advanced superconducting tokamak.

A 5-channel Doppler backscattering system has been designed and installed in the Experimental Advanced Superconducting Tokamak (EAST). Through an I/Q-type double sideband modulator and a frequency multiplier, an array of finely spaced (Δf = 400 MHz) frequencies that span 1.6 GHz has been created. The center of the array bandwidth is tunable within the range of 75-97.8 GHz, which covers most of the W band (75-110 GHz). The incident angle can be adjusted from -4° to 12°, and the wavenumber range is 4-15 cm-1 with a wavenumber resolution of Δk/k ≤ 0.35. Ray tracing is used to calculate the scattering location and the scattering wavenumber. This article details the hardware design, the ray tracing, and the preliminary experimental results from EAST plasmas.

Impact of E × B shear flow on low-n MHD instabilities.

Recently, the stationary high confinement operations with improved pedestal conditions have been achieved in DIII-D [K. H. Burrell et al., Phys. Plasmas 23, 056103 (2016)], accompanying the spontaneous transition from the coherent edge harmonic oscillation (EHO) to the broadband MHD turbulence state by reducing the neutral beam injection torque to zero. It is highly significant for the burning plasma devices such as ITER. Simulations about the effects of E × B shear flow on the quiescent H-mode (QH-mode) are carried out using the three-field two-fluid model in the field-aligned coordinate under the BOUT++ framework. Using the shifted circular cross-section equilibriums including bootstrap current, the results demonstrate that the E × B shear flow strongly destabilizes low-n peeling modes, which are mainly driven by the gradient of parallel current in peeling-dominant cases and are sensitive to the Er shear. Adopting the much more general shape of E × B shear ([Formula: see text]) profiles, the linear and nonlinear BOUT++ simulations show qualitative consistence with the experiments. The stronger shear flow shifts the most unstable mode to lower-n and narrows the mode spectrum. At the meantime, the nonlinear simulations of the QH-mode indicate that the shear flow in both co- and counter directions of diamagnetic flow has some similar effects. The nonlinear mode interaction is enhanced during the mode amplitude saturation phase. These results reveal that the fundamental physics mechanism of the QH-mode may be shear flow and are significant for understanding the mechanism of EHO and QH-mode.

The association of anti-platelet factor 4/heparin antibodies with early and delayed thromboembolism after cardiac surgery.

Essentials We evaluated antibody status, thromboembolism and survival after cardiac surgery. Positive antibody tests are common - over 50% are seropositive at 30 days. Seropositivity did not increase thromboembolism or impair survival after cardiac surgery. Results show heparin induced thrombocytopenia antibody screening after surgery is not warranted. SUMMARY: Background Heparin-induced thrombocytopenia (HIT) is a prothrombotic response to heparin therapy with platelet-activating, anti-platelet factor 4 (PF4)/heparin antibodies leading to thrombocytopenia associated with thromboembolism. Objective We tested the hypothesis that anti-PF4/heparin antibodies are associated with thromboembolism after cardiac surgery. Methods This multicenter, prospective cohort study collected laboratory and clinical data up to 30 days after surgery and longer-term clinical follow-up data. The primary outcome variable combined new arterial or venous thromboembolic complications (TECs) with all-cause death until 90 days after surgery. Laboratory analyses included platelet counts and anti-PF4/heparin antibody titers (GTI ELISA), with a confirmatory excess heparin step and serotonin release assay. Chi-square testing was used to test the relationship between our outcome and HIT antibody seropositivity. Results Initially, 1021 patients were enrolled between August 2006 and May 2009, and follow-up was completed in December 2014. Seropositivity defined by OD > 0.4 was common, being almost 20% preoperatively, > 30% by discharge, and > 60% by day 30. Death (1.7% within 30 days) or TECs (69 in total) were more likely if the partient was seronegative (OD < 0.4), but positivity defined by OD > 1.0 or including an excess heparin confirmatory step resulted in equal incidence of death or TECs, whether the patient was seronegative or seropositive. Incorporating the serotonin release assay for platelet-activating antibodies did not alter these findings. Conclusions Seropositivity for anti-PF4/heparin antibodies does not increase the risk of death or thromboembolism after cardiac surgery. Screening is not indicated, and seropositivity should only be interpreted in the context of clinical evidence for HIT. TRIAL REGISTRATION: Duke IRB Protocol #00010736.

Multi-channel poloidal correlation reflectometry on experimental advanced superconducting tokamak.

A new multi-channel poloidal correlation reflectometry is developed at Experimental Advanced Superconducting Tokamak. Eight dielectric resonator oscillators with frequencies of 12.5 GHz, 13.5 GHz, 14.5 GHz, 15 GHz, 15.5 GHz, 16 GHz, 17 GHz, and 18 GHz are used as sources. Signals from the sources are up-converted to V band using active quadruplers and then coupled together. The output waves are launched by one single antenna after passing through a 20 dB directional coupler which can provide the reference signal. Two poloidally separated antennae are installed to receive the reflected waves from plasma. The reference and reflected signals are down-converted by mixing with a quadrupled signal from a phase-locked source with a frequency of 14.2 GHz and the IF signals pass through the filter bank. The resulting signals from the mixers are detected by I/Q demodulators. The setup enables the measurement of density fluctuation at 8 (radial) × 2 (poloidal) spatial points. A coherent mode with an increasing velocity from 50 kHz to 100 kHz is observed by using the system. The mode is located in the steep gradient region of the pedestal.

Clinical outcomes of bivalirudin for ischemic heart disease.

BACKGROUND: Current treatment strategies for percutaneous coronary revascularization and acute coronary syndromes incorporate thrombin inhibition with either unfractionated or fractionated heparin. The peptide bivalirudin (Hirulog) is a direct thrombin inhibitor whose pharmacological properties differ from those of heparin. We conducted a systematic overview (meta-analysis) to assess the effect of bivalirudin on 4 end points: death, myocardial infarction, major hemorrhage, and the composite of death or infarction. METHODS AND RESULTS: Six trials (5674 patients) represent the randomized, controlled bivalirudin experience, including 4603 patients undergoing elective percutaneous coronary revascularization and 1071 patients with acute coronary syndromes. ORs for the 4 clinical end points were calculated for each trial. Four trials (4973 patients) that compared bivalirudin with heparin were combined with the use of a random-effects model. In these trials, bivalirudin was associated with a significant reduction in the composite of death or infarction (OR 0.73, 95% CI 0.57 to 0.95; P=0.02) at 30 to 50 days, or 14 fewer events per 1000 patients so treated. There also was a significant reduction in major hemorrhage for the same trials (OR 0.41, 95% CI 0. 32 to 0.52; P<0.001, or 58 fewer events per 1000 patients so treated). A similar analysis combined 2 dose-ranging trials (701 patients) that compared therapeutic (activated partial thromboplastin time more than twice the control time) with subtherapeutic bivalirudin anticoagulation (activated partial thromboplastin time less than twice the control time). CONCLUSIONS: Bivalirudin is at least as effective as heparin, with clearly superior safety. Thus, it provides an unprecedented net clinical benefit over heparin in patients with ischemic heart disease.

Outcome of Hispanic patients treated with thrombolytic therapy for acute myocardial infarction: results from the GUSTO-I and III trials. Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries.

OBJECTIVES: We sought to describe the differences in the process of care and clinical outcomes between Hispanics and non-Hispanics receiving thrombolytic therapy for myocardial infarction (MI). BACKGROUND: Hispanics are the fastest growing and second largest minority in the U.S. but most cardiovascular disease data on Hispanics has been derived from retrospective studies and vital statistics. Despite their higher cardiovascular risk-factor profile, better outcomes after MI have been reported in Hispanics. METHODS: We studied the baseline characteristics, resource use and outcomes of 734 Hispanics and 27,054 non-Hispanics treated for MI in the GUSTO-I and -III trials. The primary end point of both trials was 30-day mortality. RESULTS: Hispanics were younger, shorter, lighter and more often diabetic and began thrombolysis 9 min later, compared with non-Hispanics. Measures of socioeconomic status (educational level, employment and health insurance) were lower among Hispanics. Fewer Hispanics than non-Hispanics underwent in-hospital angiography (70% vs. 74%, p = 0.013) or bypass surgery (11% vs. 13.5%, p = 0.04). Hispanics received more angiotensin-converting enzyme (ACE) inhibitors and less calcium-channel blockers, prophylactic lidocaine and inotropic agents. Mortality at 30 days and at one year did not differ significantly between Hispanics and non-Hispanics (6.4% vs. 6.7% and 9.0% vs. 9.7%, respectively). We noted no interactions between thrombolytic strategy and Hispanic status on major outcomes (30-day death, stroke and major bleeding). CONCLUSIONS: The care of Hispanics with MI differed slightly from that of non-Hispanics. Nevertheless, these differences in care did not affect long-term outcomes.

Clinical experience and predicting survival in coronary disease.

To study the accuracy with which long-term prognosis can be predicted in patients with coronary artery disease, prognostic predictions obtained from a large, diverse sample of practicing cardiologists were compared with predictions from a multivariable statistical model. Test samples of 10 patients each were selected from a large series of medically treated patients with significant coronary disease. Using detailed clinical summaries, 49 cardiologists each predicted the probability of 3-year survival and infarction-free survival for 10 patients. Cox regression models, developed using patients who were not in the test samples, were also used to predict corresponding outcome probabilities for each test patient. Overall, the model estimates of prognosis were significantly better than the doctors' predictions. The rank correlation of model predictions with 3-year survival was 0.60, compared with 0.52 for the physicians. Model predictions added significant prognostic information to the doctors' predictions, whereas the converse was not true. Where predictions were made by multiple doctors, the inter-physician variability was substantial. Neither practice characteristics nor extent of clinical experience significantly affected the physicians' predictive accuracy. In coronary artery disease, statistical models developed from carefully collected data can provide prognostic predictions that are more accurate than predictions of experienced clinicians made from detailed case summaries.

Prediction of early recurrent myocardial ischemia and coronary reocclusion after successful thrombolysis: a qualitative and quantitative angiographic study.

To determine the association of qualitative and quantitative measurements of the myocardial infarct-related coronary narrowing with subsequent recurrent ischemia/reocclusion after successful thrombolysis, 47 patients treated with high-dose (150 mg) tissue plasminogen activator over 6 to 8 hours were studied in the setting of acute myocardial infarction. No patient underwent emergent coronary angioplasty. All patients had Thrombolysis in Myocardial Infarction (TIMI) grade 2 flow or higher at the baseline (90-minute) angiogram; 31 patients had a protocol 24-hour catheterization as well. Eighteen patients had recurrent ischemia/reocclusion whereas 29 had an uneventful hospital course. There was no significant difference in baseline clinical characteristics between the 2 groups. Twenty-five (86%) of those with an uneventful course had TIMI grade 3 flow at baseline angiogram compared with 56% of patients with recurrent events. No significant difference in angiographic morphologic characteristics was found between the 2 groups at baseline catheterization. At 24 hours, however, none of the patients who subsequently had recurrent events had a concentric narrowing, while 13 (58%) of them had a complex morphology. In contrast, quantitative parameters of minimal lumen diameter, percent area stenosis and percent diameter stenosis at baseline and 24 hours were not significantly different between those who did and did not have recurrent ischemia/reocclusion. These findings suggest that the degree and quality of coronary flow at baseline catheterization are more important determinants of sustained patency and event-free hospitalization than are quantitative dimensions or coronary morphology. In addition, narrowings that fail to become concentric within the first 24 hours are more likely to be associated with subsequent ischemia or reocclusion during the early periinfarct period.

Outcomes following interventions in small coronary arteries with the use of hand-crimped Palmaz-Schatz stents.

Although coronary stenting has been shown to be effective, retrospective studies have suggested that stents do not provide better results than angioplasty in small coronary arteries. We sought to examine procedural, in-hospital, and long-term outcomes of patients undergoing small-vessel stenting with Palmaz-Schatz stents hand-crimped on a balloon catheter <3 mm in diameter. We retrospectively analyzed the outcomes of 117 patients who underwent this type of coronary stent implantation at Duke University Medical Center between January 1, 1997 and May 30, 1998. The clinical indications for percutaneous revascularization included unstable angina in 67.5% of patients, acute myocardial infarction in 4.3%, postinfarct angina in 3.4%, silent ischemia in 3.4%, and stable angina in 1% of patients. Quantitative angiographic analysis was performed immediately before angioplasty and after stent implantation. Stents were used for elective indications in 24%, for suboptimal angiographic result in 61.5%, and for abrupt and/or threatened closure in 14.5% of patients. Reference vessel diameter was similar before and after the procedure. Minimum luminal diameter increased from 0.63 to 2.35 mm, an acute gain of 1.72+/-0.43 mm. Percent stenosis decreased from 74.2% to 4.7%. The clinical composite of death (n = 1, 1%), nonfatal myocardial infarction (n = 6, 5.1%), and revascularization (n = 1, 1%) occurred in-hospital in only 8 patients (6.8%), resulting in clinical procedure success in 109 patients (93%). Our data suggest that stents designed for vessels >3.0 mm can be deployed in small vessels, with a low in-hospital event rate. However, target lesion revascularization in small vessels remains high. Development of antiproliferative strategies could improve long-term outcomes for small-vessel interventions.

Glycoprotein IIb/IIIa receptor antagonists in non-ST elevation acute coronary syndromes and percutaneous revascularisation: a review of trial reports.

Acute coronary syndromes and percutaneous coronary interventions share a common pathophysiological mechanism of intimal disruption and platelet aggregation. Glycoprotein (GP) IIb/IIIa receptor antagonists, which interrupt the final common pathway of platelet activation and aggregation, have been shown to have clear clinical benefit as acute therapy. Treatment of 1000 patients with parenteral formulations prevents at least 1 death, 20 deaths or myocardial infarctions (MIs), and 30 deaths, MIs or revascularisation procedures over a 30-day period. These benefits are sustained at 6 months. Clinical trials of oral formulations are underway. The challenges of dose, haemorrhage and thrombocytopenia must be surmounted before oral antagonists can be incorporated into clinical practice. Despite enrolment of thousands of patients in randomised trials of GPIIb/IIIa antagonists, much additional information is needed to refine the use of this therapy in practice. Application of this drug class will advance a new therapeutic standard for ischaemic heart disease.

The health care burden of unstable angina.

Worldwide, UA represents a significant allocation of resources. UA represents a syndrome where not only do many therapies exist, but considerable clinical trial evidence has accumulated. Universal application of effective practice patterns is warranted if we are to successfully reduce the burden of UA. Economic analyses cannot resolve many of the underlying societal issues that affect decision making. Often, the acceptability of an economic burden is dependent on the willingness of both individuals and society to pay. In an interesting study, Chestnut et al evaluated the willingness of 50 patients to pay for avoiding a worsening of their angina symptoms. On average, the patients were willing to pay between $210 and $499 to avoid four to eight additional angina episodes each month. The "rule of rescue" suggests that society is often willing to pay large sums of money to save those in extreme need, such as the 55-year-old man rushed to the emergency department clutching his chest. Only recently has attention been paid to how much this disease entity costs us. Whereas the 1980s and 1990s saw a focus on costs, the next century will increasingly focus on value--obtaining the best health outcome for the dollars spent. Debate has shifted, at least in part, from purely financial costs to medical effectiveness and outcomes management. Continuing assessments of value of interventions and application of evidence based-management strategies permit rational selection of therapy and allow us best to bear the burden of UA.

Echocardiographic risk stratification for early surgery with endocarditis: a cost-effectiveness analysis.

BACKGROUND: Despite widespread acceptance of echocardiography for diagnosis of infective endocarditis, few investigators have evaluated its utility as a risk-stratification tool to aid therapeutic decision-making. METHODS: A decision tree and Markov analysis model were constructed using published and institutional data to estimate the cost-effectiveness of an echocardiographic risk-stratification strategy for infective endocarditis. The models compared surgery for high-risk patients based on clinical factors ("standard care") and surgery for high-risk patients based on echocardiographic findings ("echocardiography-guided"). RESULTS: The cost per patient for standard care and echocardiography-guided strategies was $47,766 and $53,669, respectively. The expected quality-adjusted life years (QALY) for standard care and echocardiography-guided strategies were 5.86 years and 6.10 years, respectively. Compared with standard care, the echocardiography-guided strategy cost an additional $23,867 per QALY saved. In one-way sensitivity analyses, the incremental cost of this strategy remained <$50,000/QALY across a broad range of scenarios. Baseline stroke risk had the greatest effect on cost-effectiveness. For populations with stroke risk less than 3.65%, the echocardiography-guided strategy was not cost-attractive (ICER >$50,000/QALY). At stroke risk between 3.65% and 14%, the ICER for the echocardiography-guided strategy was attractive (<$50,000 /QALY). The echocardiography-guided strategy became economically dominant at any baseline stroke risk greater than 18.3%. CONCLUSION: Echo-guided risk stratification for early surgery in patients with large vegetations is a cost-attractive treatment strategy for IE, as it improves outcome for an incremental cost <$50,000/QALY.

Advances in the approach to acute coronary syndromes.

Acute coronary syndromes is a new term that encompasses the many permutations of acute ischemic heart disease. Management guidelines can help steer clinicians through diagnosis and facilitate rational selection of therapy from the myriad of available treatments.