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Abstract Background Acute myeloid leukemia (AML) is a hematopoietic malignancy with poor outcomes, especially in older AML patients. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is considered a promising anticancer drug because it selectively induces the extrinsic apoptosis of tumor cells without affecting normal cells. However, clinical trials have shown that the responses of patients to TRAIL are significantly heterogeneous. It is necessary to explore predictable biomarkers for the preselection of AML patients with better responsiveness to TRAIL. Here, we investigated the critical role of tumor protein p53 inducible nuclear protein 2 (TP53INP2) in the AML cell response to TRAIL treatment. Methods First, the relationship between TP53INP2 and the sensitivity of AML cells to TRAIL was determined by bioinformatics analysis of Cancer Cell Line Encyclopedia datasets, Cell Counting Kit-8 assays, flow cytometry (FCM) and cell line-derived xenograft (CDX) mouse models. Second, the mechanisms by which TP53INP2 participates in the response to TRAIL were analyzed by Western blot, ubiquitination, coimmunoprecipitation and immunofluorescence assays. Finally, the effect of TRAIL alone or in combination with the BCL-2 inhibitor venetoclax (VEN) on cell survival was explored using colony formation and FCM assays, and the effect on leukemogenesis was further investigated in a patient-derived xenograft (PDX) mouse model. Results AML cells with high TP53INP2 expression were more sensitive to TRAIL in vitro and in vivo. Gain- and loss-of-function studies demonstrated that TP53INP2 significantly enhanced TRAIL-induced apoptosis, especially in AML cells with nucleophosmin 1 (NPM1) mutations. Mechanistically, cytoplasmic TP53INP2 maintained by mutant NPM1 functions as a scaffold bridging the ubiquitin ligase TRAF6 to caspase-8 (CASP 8), thereby promoting the ubiquitination and activation of the CASP 8 pathway. More importantly, simultaneously stimulating extrinsic and intrinsic apoptosis signaling pathways with TRAIL and VEN showed strong synergistic antileukemic activity in AML cells with high levels of TP53INP2. Conclusion Our findings revealed that TP53INP2 is a predictor of responsiveness to TRAIL treatment and supported a potentially individualized therapeutic strategy for TP53INP2-positive AML patients.

Abstract Background Skin cutaneous melanoma (SKCM) is an extremely malignant tumor that is associated with a poor prognosis. LSM2 has been found to be related to different types of tumors; however, its role in SKCM is poorly defined. We aimed to determine the value of LSM2 as a prognostic biomarker for SKCM. Methods The expression profile of LSM2 mRNA was compared between tumor and normal tissues in public databases, such as TCGA, GEO, and BioGPS. LSM2 protein expression was explored using immunohistochemistry (IHC) on a tissue microarray containing 44 SKCM tissues and 8 normal samples collected at our center. Kaplan-Meier analysis was performed to assess the prognostic value of LSM2 expression in patients with SKCM. SKCM cell lines with LSM2 knockdown were used to determine the effects of LSM2. Cell counting kit-8 (CCK8) and colony formation assays were conducted to assess cell proliferation, whereas wound healing and transwell assays were carried out to assess the migration and invasion abilities of SKCM cells. Results LSM2 was more highly expressed at the mRNA and protein levels in SKCM than that in normal skin. Moreover, elevated expression of LSM2 was associated with shorter survival time and early recurrence in patients with SKCM. The in vitro results revealed that the silencing of LSM2 in SKCM cells significantly inhibited cell proliferation, migration, and invasion. Conclusion Overall, LSM2 contributes to malignant status and poor prognosis in patients with SKCM and may be identified as a novel prognostic biomarker and therapeutic target.

The main purpose of this article is to use some identities of the classical Gauss sums, the properties of character sums, and Dedekind sums (modulo an odd prime) to study the computational problem of one-kind mean values related to Dedekind sums and give some interesting identities for them.

Abstract Background WRINKLED1 (WRI1) encodes a transcription factor, belonging to the APETALA2 (AP2) family, and plays a key role in regulating plant oil biosynthesis. As a newly woody oil crop, tree peony (Paeonia rockii) was notable for the abundant unsaturated fatty acids in its seed oil. However, the role of WRI1 during the accumulation of P. rockii seeds oil remains largely unknown. Results In this study, a new member of the WRI1 family was isolated from P. rockii and was named PrWRI1. The ORF of PrWRI1 consisted of 1269 nucleotides, encoding a putative protein of 422 amino acids, and was highly expressed in immature seeds. Subcellular localization analysis in onion inner epidermal cells showed that PrWRI1 was located at the nucleolus. Ectopic overexpression of PrWRI1 could significantly increase the total fatty acid content in Nicotiana benthamiana leaf tissue and even PUFAs in transgenic Arabidopsis thaliana seeds. Furthermore, the transcript levels of most genes related to fatty acids (FA) synthesis and triacylglycerol (TAG) assembly were also up-regulated in transgenic Arabidopsis seeds. Conclusions Together, PrWRI1 could push carbon flow to FA biosynthesis and further enhance the TAG amount in seeds with a high proportion of PUFAs.

Objective: To investigate the CT manifestations of primary intestinal lymphoma (PIL) so as to improve the diagnosis and differential diagnosis. Methods: 21 patients with PIL confirmed pathologically in our hospital from March 2013 to February 2022 were enrolled in this study, their CT phenotypes and features were analyzed. Results: All 21 cases of PIL were non-Hodgkin's lymphoma (NHL), 12 cases were diffuse large B-cell lymphoma (DLBCL), 3 cases were follicular lymphoma, 2 cases were NK/T-cell lymphoma, 2 cases were T-cell lymphoma, mucosa-associated lymphoid tissue lymphoma (MALT) and mantle cell lymphoma (MCL) were identified 1 case each. The lesions were located in the colon in 7 cases, ileum in 5 cases, small intestine mesentery in 4 cases, ileocecum in 2 cases, jejunum in 1 case, rectum in 1 case, and both right hemicolon and ileocecum in 1 case. CT findings showed intestinal wall infiltration in 3 cases, intestinal wall thickening in 3cases, mass in 4 cases, aneurysmal dilation in 7 cases and mesenteric multiple nodules in 4 cases. CT enhancement mostly showed homogeneous mild/moderate enhancement. Among the 21 patients, 2 case was complicated by by intestinal perforation, and 2 cases were complicated by intestinal obstruction. Conclusion: The characteristic imaging features of CT in PIL include multifocal involvement of the intestines, marked mural thickening in a focal or diffuse manner, aneurysmal dilatation of lumen, eccentric intestinal mass of uniform density and mesenteric "sandwich sign". Recognition of these signs is of diagnostic value for primary intestinal lymphoma.

Abstract Background Integrative medicine is commonly used in China. Researchers prefer to report efficacy outcomes rather than safety outcomes in clinical trials; thus, evidence regarding safety in integrative medicine is unclear. Developing a core outcome set (COS) for safety outcomes is necessary. In this study, a representative example of the methodology for developing COS to assess safety outcomes of cardiovascular diseases in clinical trials investigating integrated medicine will be developed. Methods and analysis Safety information will be extracted from package inserts and through systematic reviews of treatments for cardiovascular diseases (including angina pectoris, myocardial infarction, heart failure, arrhythmia, and hypertension) to develop an extensive list of safety outcomes, which will then be categorized according to whether subjective or objective outcomes. Questionnaires for clinician-reported safety outcomes and patient-reported safety outcomes will be developed. Two rounds of the Delphi survey will then be conducted for different stakeholders (traditional Chinese medicine clinicians and researchers in cardiovascular diseases, Western medicine clinicians and researchers in cardiovascular diseases, integrated medicine clinicians and researchers of cardiovascular diseases, pharmacologists, methodologists of evidence-based medicine, and patients). After round 2 of the Delphi analysis, a face-to-face consensus meeting will be held to determine the final COS for assessing safety outcomes in cardiovascular diseases. Discussion A COS for safety outcomes in cardiovascular diseases may improve the consistency of reporting results and will help identify potential bias of selective reporting in the future. Trial registration This study was registered in the Core Outcome Measures in Effectiveness Trials database as study 1564 .

In this article, we use the elementary methods and the estimate for character sums to study a problem related to quadratic residues and the Pythagorean triples, and prove the following result. Let $ p $ be an odd prime large enough. Then for any positive number $ 0 < \epsilon < 1 $, there must exist three quadratic residues $ x, \ y $ and $ z $ modulo $ p $ with $ 1\leq x, \ y, \ z\leq p^{1+\epsilon} $ such that the equation $ x^2+y^2 = z^2 $.

It can be seen that the corrosion failure of transmission and transformation equipment has increasingly restricted the safe operation of the Zhejiang power grid bottleneck problem. If effective anticorrosion measures are not taken promptly, transmission and transformation equipment serving in various sophisticated atmospheric environments will suffer serious corrosion damage in a relatively short period, which endangers the safe usage of transmission and transformation equipment and the security of grid operation. In this article, through the establishment of transmission and transformation steel components corrosion fracture mechanics model, a standard corrosion spectrum grading software based on DeepLabV3+ image segmentation technology is developed to determine the quantitative assessment method of corrosion damage and assess the corrosion status with safety degree of transmission and transformation equipment. According to the assessment results, the operation and maintenance units are guided to adopt differentiated corrosion maintenance and replacement strategies, so as to reduce corrosion safety hazards and reduce safety accidents and economic losses caused by corrosion, which is of great significance for the safe operation of power grids.

Abstract Background Traditional Chinese medicine (TCM) has gained widespread application in treating chronic heart failure (CHF) secondary to coronary heart disease (CHD). However, the sound clinical evidence is still lacking. Corresponding clinical trials vary considerably in the outcome measures assessing the efficacy of TCM, some that showed the improvement of clinical symptoms are not universally acknowledged. Rational outcome measures are the key to evaluate efficacy and safety of each treatment and significant elements of a convincing clinical trial. We aimed to summarize and analyze outcome measures in randomized controlled trials (RCTs) of TCM in treating CHF caused by CHD, subsequently identify the present problems and try to put forward solutions. Methods We systematically searched databases including Embase, PubMed, Cochrane Library, CBM, CNKI, VIP and Wanfang from inception to October 8, 2018, to identify eligible RCTs using TCM interventions for treating CHF patients caused by CHD. Cochrane Database of Systematic Reviews (CDSR) was searched to include Cochrane systematic reviews (CSRs) of CHF. Two authors independently assessed the risk of bias of the included RCTs according to the Cochrane Handbook. Outcome measures of each trial were extracted and analyzed those compared with the CSRs. We also evaluated the reporting quality of the outcome measures. Results A total of 31 RCTs were included and the methodology quality of the studies was generally low. Outcome measures in these RCTs were mortality, rehospitalization, efficacy of cardiac function, left ventricular ejection fraction (LVEF), 6 min’ walk distance (6MWD) and Brain natriuretic peptide (BNP), of which mortality and rehospitalization are clinical end points while the others are surrogate outcomes. The reporting rate of mortality and rehospitalization was 12.90% (4/31), the other included studies reported surrogate outcomes. As safety measure, 54.84% of the studies reported adverse drug reactions. Two trials were evaluated as high in reporting quality of outcomes and that of the other 29 studies was poor due to lack of necessary information for reporting. Conclusions The present RCTs of TCM in treating CHF secondary to CHD did not concentrate on the clinical end points of heart failure, which were generally small in size and short in duration. Moreover, these trials lacked adequate safety evaluation, had low quality in reporting outcomes and certain risk of bias in methodology. For objective assessment of the efficacy and safety of TCM in treating CHF secondary to CHD, future research should be rigorous designed, set end points as primary outcome measures and pay more attention to safety evaluation throughout the trial.

Let $ k $ be a fixed positive integer with $ k > 1 $. In 2014, N. Terai [6] conjectured that the equation $ x^2+(2k-1)^y = k^z $ has only the positive integer solution $ (x, y, z) = (k-1, 1, 2) $. This is still an unsolved problem as yet. For any positive integer $ n $, let $ Q(n) $ denote the squarefree part of $ n $. In this paper, using some elementary methods, we prove that if $ k\equiv 3 $ (mod 4) and $ Q(k-1)\ge 2.11 $ log $ k $, then the equation has only the positive integer solution $ (x, y, z) = (k-1, 1, 2) $. It can thus be seen that Terai's conjecture is true for almost all positive integers $ k $ with $ k\equiv 3 $(mod 4).

The location of the grounding grid conductors is critical for performing corrosion diagnosis and maintenance work. An improved magnetic field differential method to locate the unknown grounding grid based on truncation errors and the round-off errors analysis is presented in this paper. It was proven that a different order of the magnetic field derivative can be used to determine the position of the grounding conductor according to the peak value of the derivative. Due to the accumulative error of higher differentiation, the truncation error and rounding error were used to analyze to accumulative error and to determine the optimal step size to measure and calculate the higher differentiation. The possible range and probability distribution of the two kinds of errors at each order are described, and the index of peak position error was derived, which can be used to locate the grounding conductor in the power substation.

Modern crowdsourcing offers the potential to produce solutions for increasingly complex tasks requiring teamwork and collective labor. However, the vast scale of the crowd makes forming project teams an intractable problem to coordinate manually. To date, most crowdsourcing collaborative platforms rely on algorithms to automate team formation based on worker profiling data and task objectives. As a top-down strategy, algorithmic crowd team formation tends to alienate workers causing poor collaboration, interpersonal clashes, and dissatisfaction. In this paper, we investigate different ways that crowd teams can be formed through three team formation models namely bottom-up, top-down, and hybrid. By simulating an open collaboration scenario such as a hackathon, we observe that the bottom-up model forms the most competitive teams with the highest teamwork quality. Furthermore, we note that bottom-up approaches are particularly suitable for populations with high-risk appetites (most workers being lenient toward exploring new team configurations) and high degrees of homophily (most workers preferring to work with similar teammates). Our study highlights the importance of integrating worker agency in algorithm-mediated team formation systems, especially in collaborative/competitive settings, and bears practical implications for large-scale crowdsourcing platforms.

Abstract Aims We aim to assess the effect of a lyophilized herbal injection on 90 day mortality and readmission rates in patients with acute heart failure (AHF). Methods and results The AUGUST‐AHF study is a multicentre, randomized, double‐blind, placebo‐controlled trial enrolling 1270 hospitalized patients for AHF. Patients are randomized to receive YiqiFumai lyophilized injection (5.2 g/day) or placebo for 10 days, in addition to standard therapy, using a 1:1 ratio via an interactive web response system. The primary endpoint is the 90 day all‐cause mortality or AHF readmission rates. Secondary endpoints include 180 day all‐cause mortality or heart failure readmission rates, length of hospital stay for the indexed AHF, 90 day cardiac‐specific mortality rate, occurrence of worsening heart failure through Day 10, changes in the Minnesota Living with Heart Failure Quality of Life scale score through Day 180, and 90 day major adverse cardiac events. Additional secondary endpoints include change in dyspnoea via visual analogue scale (VAS) and Likert 7‐point comparator scale, N terminal pro‐B‐type natriuretic peptide value and New York Heart Association functional class, and the total amount of diuretics for the indexed AHF hospitalization. Study recruitment is expected to be completed by March 2021, and follow‐up will end in September 2021. In an optional sub‐study, patients will be followed up for 3 years. Conclusions To our best knowledge, AUGUST‐AHF is the first study assessing the efficacy of a Chinese herbal injection in patients with AHF. The results will be valuable to guide clinicians in using YiqiFumai lyophilized injection, which was included in the latest Chinese Health Insurance Catalog.

Abstract Background No treatment has convincingly been proven to be beneficial for microvascular obstruction (MVO) in patients with ST-elevation myocardial infarction (STEMI). Several studies have described the effects of Danhong Injection. However, evidence of a rigorously designed verification study is still lacking, and the intervention timing of Danhong Injection is uncertain. Methods The DIRECTION study is a multicenter, prospective, randomized, evaluator-blind study. A total of 336 patients with STEMI receiving percutaneous coronary intervention (PCI) will be randomly assigned to conventional treatment, the preoperative Danhong Injection, or the postoperative Danhong Injection. The primary outcome is rate of ST-segment resolution (STR) ≥ 70% at 90 min after PCI. The secondary outcomes are the degree of STR, Thrombolysis in Myocardial Infarction (TIMI) flow grade, TIMI myocardial perfusion grade, left ventricular ejection fraction, N-terminal prohormone brain natriuretic peptide, high-sensitivity C-reactive protein, and infarct size expressed as area under the curve for cardiac troponin I (cTnI) and for creatine kinase MB. The major adverse cardiovascular events and hospital readmission events will be recorded. Health quality will be assessed with the 12-item Short Form Health Survey. The safety outcomes include bleeding events, adverse events, and abnormal changes in routine blood tests. Psychological status and dietary patterns will be evaluated using Hamilton Depression Rating Scale and Food Frequency Questionnaire as the relevant indicators. Discussion This trial will evaluate the efficacy and safety of Danhong Injection, as well as its optimal timing of intervention to prevent MVO in patients with STEMI. Trial registration Chinese Clinical Trial Registry, ChiCTR1900021440. Registered on February 21, 2019.

In many higher plants, seed oil accumulation is governed by complex multilevel regulatory networks including transcriptional regulation, which primarily affects fatty acid biosynthesis. Tree peony (Paeonia rockii), a perennial deciduous shrub endemic to China is notable for its seed oil that is abundant in unsaturated fatty acids. We discovered that a tree peony trihelix transcription factor, PrASIL1, localized in the nucleus, is expressed predominantly in developing seeds during maturation. Ectopic overexpression of PrASIL1 in Nicotiana benthamiana leaf tissue and Arabidopsis thaliana seeds significantly reduced total fatty acids and altered the fatty acid composition. These changes were in turn associated with the decreased expression of multitudinous genes involved in plastidial fatty acid synthesis and oil accumulation. Thus, we inferred that PrASIL1 is a critical transcription factor that represses oil accumulation by down-regulating numerous key genes during seed oil biosynthesis. In contrary, up-regulation of oil biosynthesis genes and a significant increase in total lipids and several major fatty acids were observed in PrASIL1-silenced tree peony leaves. Together, these results provide insights into the role of trihelix transcription factor PrASIL1 in controlling seed oil accumulation. PrASIL1 can be targeted potentially for oil enhancement in tree peony and other crops through gene manipulation.

To ensure the speed, recall, and precision of the algorithm to solve the algorithm’s measurement failure due to the problem of high underdetermination and the deviation of some outgoing lines from accessible nodes, the ideal resistance method is proposed to diagnose the corrosion of the grounding grid. The information extraction algorithm, a two-way heuristic network resistance diagnosis method, is added. A non-linear multi-objective optimization model of the deviation between the measured potential and the real potential is established. This paper puts forward that the grounding network’s fault diagnosis is analogous to a neural network’s training process, which makes full use of the excellent robustness and rapidity of a neural network training method. Simultaneously, the algorithm adds the retraining method combined with the field excavation in training and proves its feasibility through the Grobner basis codimension theory in algebraic geometry. Through result verification, it is found that the new algorithm can avoid the inversion failure caused by the algorithm failure due to the lack of accessible nodes and the abnormal part of input data at the same time as a fast solution.

Aims: To identify a minimum set of efficacy and adverse events for patients with acute heart failure (AHF) among different stakeholders in clinical trials of traditional Chinese medicine and Western medicine.Methods and Analysis: First, we will develop a preliminary long list of outcomes that includes efficacy and adverse events/reactions via three steps: (i) systematic reviews of efficacy and safety outcomes for clinical trials of AHF; (ii) drugs included in the National Medical Insurance Catalog, the National Essential Medicines Catalog, and the WHO Essential Medicines List will be collected and safety outcomes extracted from the package inserts; and (iii) patients' or caregivers' semi-structured interviews will be carried out to add new viewpoints to the list. Second, after merging outcomes and grouping them under different outcome domains, questionnaires for health professionals and patients will be separately developed. Further, two rounds of Delphi survey for health professionals and a survey for patients and the public will be carried out. Third, different stakeholders will discuss and determine the final core outcome set (COS) for AHF in a consensus meeting.Ethics and Dissemination: The entire project has been approved by the Ethics Committee of the main institution. After the final COS is developed, it will be published and discussed widely in conferences.Clinical Trial Registration: This study is registered with the Core Outcome Measures in Effectiveness Trials database as study 1566 (available at: https://www.cometinitiative.org/Studies/Details/1566).

The main purpose of this paper is using analytic methods and the properties of the Dedekind sums to study one kind hybrid power mean calculating problem involving the Dedekind sums and cubic Gauss sum and give some interesting calculating formulae for it.

For each integer n, denote by ppn the largest prime ≤n and by Ppn the smallest prime ≥n, called as the Smarandache inferior prime part and superior prime part of n, respectively. Define In≔1/n∑m≤nppm and Sn≔1/n∑m≤nPpm. In this short note, we proved some estimates on In−Sn and In/Sn, answering a question proposed by Kashihara and improving a result of Yan.

BackgroundDevelopment of a core outcome set (COS) for clinical trials for COVID-19 is urgent because of the pandemic wreaking havoc worldwide and the heterogeneity of outcomes in clinical trials.MethodsA preliminary list of outcomes was developed after a systematic review of protocols of clinical trials for COVID-19. Then, two rounds of the Delphi survey were conducted. Stakeholders were traditional Chinese medicine (TCM) experts, Western medicine (WM) experts, nurses, and the public. Patients with confirmed COVID-19 were also invited to participate in a questionnaire written in understandable language. Then different stakeholders participated in a consensus meeting by video conference to vote.ResultsNinety-seven eligible study protocols were identified from 160 clinical trials. Seventy-six outcomes were identified from TCM clinical trials and 126 outcomes were identified from WM clinical trials. Finally, 145 outcomes were included in the first round of the Delphi survey. Then, a COS for clinical trials of TCM and WM was developed. The COS included clinical outcomes (recovery/improvement/progression/death), etiology (SARS-CoV-2 nucleic-acid tests, viral load), inflammatory factor (C-reactive protein), vital signs (temperature, respiration), blood and lymphatic-system parameters (lymphocytes, virus antibody), respiratory outcomes (pulmonary imaging, blood oxygen saturation, PaO2/FiO2 ratio, arterial blood gas analysis, mechanical ventilation, oxygen intake, pneumonia severity index), clinical efficacy (prevalence of preventing patients with mild-to-moderate disease progressing to severe disease), and symptoms (clinical symptom score). Outcomes were recommended according to different types of disease. Outcome measurement instruments/definitions were also recommended.ConclusionThough there are some limitations for the research, such as insufficient patients and the public involvement, and the unbalanced stakeholders' region, the COS for COVID-19 may improve consistency of outcome reporting in clinical trials. It also should be updated with research progression.

Abstract Let p be a prime with p≡1mod8 $p\equiv1\bmod8$, ψ be an eighth character modp, and τ(ψ) $\tau(\psi)$ denote the classical Gauss sum modp. The main purpose of this paper is using the analytic method and the properties of the classical Gauss sum to study the computational problem of one kind rational polynomial of τ(ψ) $\tau(\psi)$. In the end, we prove an interesting second-order linear recursive formula for it.

The main purpose of this paper is using the analytic method and the properties of the classical Gauss sums to study the computational problem of one kind fourth hybrid power mean of the quartic Gauss sums and Kloosterman sums, and give an exact computational formula for it.

Objectives To examine variation in outcomes, outcome measurement instruments (OMIs) and measurement times in clinical trials of non-valvular atrial fibrillation (NVAF) and to identify outcomes for prioritisation in developing a core outcome set (COS) in this field.Design This study was a systematic review.Data sources Clinical trials published between January 2015 and March 2019 were obtained from PubMed, the Cochrane Library, Web of Science, Wanfang Database, the China National Knowledge Infrastructure and SinoMed.Eligibility criteria Randomised controlled trials (RCTs) and observational studies were considered. Interventions included traditional Chinese medicine and Western medicine. The required treatment duration or follow-up time was ≥4 weeks. The required sample size was ≥30 and≥50 in each group in RCTs and observational studies, respectively. We excluded trials that aimed to investigate the outcome of complications of NVAF, to assess the mechanisms or pharmacokinetics, or for which full text could not be acquired.Data extraction and synthesis The general information and outcomes, OMIs and measurement times were extracted. The methodological and outcome reporting quality were assessed. The results were analysed by descriptive analysis.Results A total of 218 articles were included from 25 255 articles. For clinical trials of antiarrhythmic therapy, 69 outcomes from 16 outcome domains were reported, and 28 (31.82%, 28/88) outcomes were reported only once; the most frequently reported outcome was ultrasonic cardiogram. Thirty-one outcomes (44.93%, 31/69) were provided definitions or OMIs; the outcome measurement times ranged from 1 to 20 with a median of 3. For clinical trials of anticoagulation therapy, 82 outcomes from 18 outcome domains were reported; 38 (29.23%, 38/130) outcomes were reported only once. The most frequently reported outcome was ischaemic stroke. Forty (48.78%, 40/82) outcomes were provided OMIs or definitions; and the outcome measurement times ranged from 1 to 27 with a median of 8.Conclusion Outcome reporting in NVAF is inconsistent. Thus, developing a COS that can be used in clinical trials is necessary.

Tree peony is a perennial deciduous shrub with great ornamental and medicinal value. A limitation of its current functional genomic research is the lack of effective molecular genetic tools. Here, the first application of a Tobacco rattle virus (TRV)-based virus-induced gene silencing (VIGS) in the tree peony species Paeonia ostii is presented. Two different approaches, leaf syringe-infiltration and seedling vacuum-infiltration, were utilized for Agrobacterium-mediated inoculation. The vacuum-infiltration was shown to result in a more complete Agrobacterium penetration than syringe-infiltration, and thereby determined as an appropriate inoculation method. The silencing of reporter gene PoPDS encoding phytoene desaturase was achieved in TRV-PoPDS-infected triennial tree peony plantlets, with a typical photobleaching phenotype shown in uppermost newly-sprouted leaves. The endogenous PoPDS transcripts were remarkably down-regulated in VIGS photobleached leaves. Moreover, the green fluorescent protein (GFP) fluorescence was detected in leaves and roots of plants inoculated with TRV-GFP, suggesting the capability of TRV to silence genes in various tissues. Taken together, the data demonstrated that the TRV-based VIGS technique could be adapted for high-throughput functional characterization of genes in tree peony.

Background: Chinese patent medicine Tongxinluo capsule (TXL) is commonly used for cardio-cerebrovascular diseases. Previous research had demonstrated that TXL exhibited great clinical effects on the treatment of acute myocardial infarction (AMI), however there is a lack of systematic review. The purpose of this study was to evaluate the potential effectiveness and safety of TXL for secondary prevention in patients with AMI.Method: We searched 6 databases to identify relevant randomized controlled trials (RCTs) from inceptions to December 30, 2017. Two review authors independently assessed the methodological quality and analyzed data by the RevMan 5.3 software. The publication bias was assessed through funnel plot and Begg's test. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used for evaluating the quality of evidence.Results: We included 19 RCTs in this review and performed a meta-analysis based on 16 studies. There were statistical differences of TXL treatment group in reducing primary cardiovascular events (cardiac death [RR = 0.27, 95%CI: 0.08~0.95, I2 = 0%], recurrent myocardial reinfarction [RR = 0.38, 95%CI: 0.20~0.74, I2 = 0%], arrhythmia [RR = 0.44, 95%CI: 0.30~0.66, I2 = 0%], recurrent angina pectoris [RR = 0.34, 95%CI: 0.17~0.69, I2 = 0%]). TXL could improve cardiac function (LVEF [MD = 4.10, 95%CI: 3.95~4.25, I2 = 0%]), regulate blood lipid TC [MD = −0.66, 95%CI: −0.94 ~ −0.37, I2 = 74%], TG [MD = −0.38, 95%CI: −0.62 ~ −0.14, I2 = 70%], LDL-C[−0.40, 95%CI: −0.65 ~ −0.16, I2 = 88%), decrease the level of hs-CRP (4-week: MD = −0.78, 95%CI: −0.97 ~ −0.60, I2 = 20%; Over 4-week: MD = −1.36, 95%CI: −1.55 ~ −1.17, I2 = 20%). However, TXL has little effects on revascularization [RR = 0.45, 95%CI: 0.13~1.56, I2 = 0%], recurrent heart failure (RR = 0.83, 95%CI: 0.27~2.57, I2 = 0%), and HDL-C (MD = 0.14, 95%CI: 0.00 ~0.29, I2 = 73%). Furthermore, TXL treatment group was more prone to suffer gastrointestinal discomfort.Conclusion: Chinese patent medicine TXL seemed beneficial for secondary prevention after AMI. This potential benefit needs to be further assessed through more rigorous RCTs.Systematic review registration number in the PROSPERO register: CRD42017068417.

Tree peony (Paeonia section Moutan DC.) species are woody oil crops with high unsaturated fatty acid content, including α-linolenic acid (ALA/18:3; >40% of the total fatty acid). Comparative transcriptome analyses were carried out to uncover the underlying mechanisms responsible for high and low ALA content in the developing seeds of P. rockii and P. lutea, respectively. Expression analysis of acyl lipid metabolism genes revealed upregulation of select genes involved in plastidial fatty acid synthesis, acyl editing, desaturation, and triacylglycerol assembly in seeds of P. rockii relative to P. lutea. Also, in association with ALA content in seeds, transcript levels for fatty acid desaturases (SAD, FAD2, and FAD3), which encode enzymes necessary for polyunsaturated fatty acid synthesis, were higher in P. rockii compared to P. lutea. Furthermore, the overexpression of PrFAD2 and PrFAD3 in Arabidopsis increased linoleic and ALA content, respectively, and modulated the final ratio 18:2/18:3 in the seed oil. In conclusion, we identified the key steps and validated the necessary desaturases that contribute to efficient ALA synthesis in a woody oil crop. Together, these results will aid to increase essential fatty acid content in seeds of tree peonies and other crops of agronomic interest.