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The effect of Pseudomonas aeruginosa (P. aeruginosa) on the phytoremediation efficiency of ryegrass on soil contaminated with nonylphenol (NP) and cadmium (Cd) was investigated by pot experiments. Pseudomonas aeruginosa application stimulated the adsorption of Cd by ryegrass and facilitated the biodegradation of NP in the soil. Exogenous P. aeruginosa inoculation increased the activities of urease, dehydrogenase, and polyphenol oxidase in the soil of the T4 treatment by 38.5%, 50.0%, and 56.5% compared to that of the T2 treatment, respectively. There was a significant positive correlation between the activities of dehydrogenase and polyphenol oxidase and the NP removal rate (P 0.001). The relative abundances of beneficial microorganisms (such as Sphingomonas, Lysobacter, Streptomyces, Chloroflexia, Deltaproteobacteria, and Alphaproteobacteria) were increased as a result of P. aeruginosa inoculation. These microorganisms play important roles in nutrient cycling, Cd adsorption, and NP degradation. Additionally, P. aeruginosa was not the dominate bacterial species at the end of the experiment. According to this study, P. aeruginosa application improved the phytoremediation efficiency of ryegrass on soil contaminated with NP and Cd, with a minimal risk of alien microbial invasion.

As the most prevalent bone tumor in children and adolescents, the pathogenesis and metastasis of osteosarcoma (OS) remain largely unclear. Here, we investigated the expression and function of a novel circular RNA (circRNA), circROCK1-E3/E4, which is back-spliced from exons 3 and 4 of Rho-associated coiled-coil containing protein kinase 1 (ROCK1) in OS. We found that circROCK1-E3/E4, regulated by the well-known RNA-binding protein quaking (QKI), was downregulated in OS and correlated with unfavorable clinical features of patients with OS. Functional proliferation and cell motility assays indicated that circROCK1-E3/E4 serves as a tumor suppressor in OS cells. Mechanistically, circROCK1-E3/E4 suppressed proliferation and migration by upregulating phosphatase and tensin homolog (PTEN) through microRNA-532-5p (miR-532-5p) sponging. In the constructed nude mouse model, circROCK1-E3/E4 inhibited tumor growth and lung metastasis in vivo. This study demonstrates the functions and molecular mechanisms of circROCK1-E3/E4 in the progression of OS. These findings may identify novel targets for the molecular therapy of OS.

Bei Tang, Ze Zhong, Jinping Wu, Jianping Ma, Li Li, Xuzheng Zhong, Dongmei Lin, Jiayuan Hu, Pingan Yu Department of Critical Care Medicine, The First People’s Hospital of Jiande City, Jiande, People’s Republic of ChinaCorrespondence: Ze Zhong, Department of Critical Care Medicine, The First People’s Hospital of Jiande City, Jiande, People’s Republic of China, Tel/Fax +86 571 64096607, Email jdsytbzz@126.comObjective: Involvement of NLR CARD domain containing 4 (NLRC4) in neuroinflammation has been demonstrated. The aim of this study was to ascertain the prognostic role of serum NLRC4 in severe traumatic brain injury (sTBI).Methods: In this prospective cohort study including 140 sTBI patients and 140 controls, serum NLRC4 levels were quantified. Follow-up time was 180 days after trauma and poor prognosis was designated as extended Glasgow outcome scale (GOSE) scores of 1– 4. Severity correlations and prognosis associations were determined under multivariate models.Results: Enhanced serum NLRC4 levels after sTBI, in comparison to controls (median, 0.8 ng/mL versus 0.1 ng/mL; P < 0.001), were independently correlated with Glasgow coma scale (GCS) scores (β, − 0.091; 95% confidence interval (CI), − 0.161— 0.021; P = 0.011), Rotterdam computed tomography (CT) scores (β, 0.136; 95% CI, 0.024– 0.248; P = 0.018), serum C-reactive protein levels (β, 0.016; 95% CI, 0.002– 0.030; P = 0.025) and 180-day GOSE scores (β, − 0.906; 95% CI, − 1.632— 0.180; P = 0.015); and were independently predictive of 180-day death (odds ratio, 4.307; 95% CI, 1.706– 10.879; P = 0.014)), overall survival (hazard ratio, 2.360; 95% CI, 1.118– 4.981; P = 0.040) and poor prognosis (odds ratio, 6.705; 95% CI, 2.889– 15.561; P = 0.016). Under receiver operating characteristic curve, combination of serum NLRC4 levels, GCS scores and Rotterdam CT scores had significantly higher death predictive ability than Rotterdam CT scores (P = 0.040), but not than GCS scores (P = 0.070); and exhibited substantially higher predictive capability for poor prognosis than Rotterdam CT scores (P < 0.001) and GCS scores alone (P = 0.023).Conclusion: There is a dramatical elevation of serum NLRC4 levels after sTBI, which has strong correlation with severity and inflammation, and is significantly associated with long-term death and poor outcome, substantializing serum NLRC4 as an inflammatory, prognostic biomarker in sTBI.Keywords: traumatic brain injury, nucleotide-binding domain leucine-rich repeat-containing protein family caspase activation and recruitment domain-containing protein 4, severity, prognosis, biomarkers, inflammation

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.

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.

Odd-parity superconductivity is recognized as a key ingredient to realize topological superconductivity. In Bi2Se3-based bulk topological superconductors, the odd-parity pairing, which spontaneously breaks the threefold rotational symmetry of the crystal, leading to a subsidiary nematic order, was discovered. The nematic superconducting state can be identified by thermodynamic measurement, nuclear magnetic resonance measurement, ac- $$\chi$$ measurement, magnetic torque measurement or magnetoresistance measurement. Here, the single crystal of topological superconductor Pd $$_x$$ Bi2Te3 was grown. Its upper critical fields were obtained by magnetoresistance measurement in various magnetic field orientations parallel to the basal plane. The in-plane upper critical fields clearly demonstrate a twofold symmetry that break the threefold crystal symmetry. This provides experimental evidence that Pd-doped Bi2Te3 is a nematic topological superconductor similar to the Cu-, Sr-, and Nb-doped Bi2Se3.

By combining angle-resolved photoemission spectroscopy (ARPES) and first-principles calculations, we have studied the electronic band structure of a topological material candidate TaPdTe5.Two inverted bulk gaps determined through the parity analysis were observed in TaPdTe5 near the Fermi level, which causes the appearance of topologically protected surface states on the (010) surface. Beside the surface state, we also observed strong surface resonance state. The hybridization between the surface resonance state and the surface state changes the quasi-one-dimensional like Fermi surface sheets of the surface resonance state into two-dimensional Fermi pockets. Our findings provide comprehensive understanding about the interesting surface states in TaPdTe5.

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.

It has been over 20 years since the introduction of evidence-based medicine (EBM) into the research of traditional Chinese medicine (TCM). The development of evidence-based TCM research has profoundly influenced the process of clinical research and decision-making, impelling researchers to pay attention to raise evidence quality, accumulate data, and explore appropriate evaluation methods adaptive to TCM original theories and knowledge. In this paper, the authors aim to summarize and review the existing work and seek promising research interests in this field, expecting to inspire more thoughts leading to breakthroughs in the near future.

Montmorillonite (MMT), as a naturally sourced and FDA-approved biomaterial, has attracted considerable attention due to its extensive application in biomedical areas, such as intestinal ailments, drug delivery, and additive manufacturing. In this work, two-dimensional montmorillonite (2D-MMT) ultrathin nanosheets were successfully prepared from sodium montmorillonite (Na-MMT) by utilizing a freeze-drying assisted method. Possessing a large specific surface area and increased number of exposed hydroxyl groups, 2D-MMT nanosheets exhibited better antibacterial ability than the original Na-MMT. More strikingly, we found that both 2D-MMT nanosheets and Na-MMT could generate reactive oxygen species (ROS) upon visible light illumination, which could promote their antibacterial efficiency. As a result, 2D-MMT nanosheets showed efficient antibacterial performance in the presence of light towards Escherichia coli with a simultaneous enhancement of surface adsorption and photodynamic ablation. What's more, a possible mechanism for ROS generation by MMT upon light illumination was first proposed in this work. The combination of the increased physical adsorption capacity and ROS generation ability of 2D-MMT nanosheets would help inspire the development of MMT as a promising antimicrobial candidate in the future.

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 $.

Two-dimensional nanomaterials are attracting attention for cancer therapy. However, high toxicity, insensitivity to external stimuli and single therapeutic modality are still key issues hindering their clinical application. Therefore, the construction of a safe, intelligent and versatile nanocomposite is needed to meet clinical expectations. Herein, we developed a nanocomposite of Bi@RP-PEG-DOX with 2D bismuthene loaded with 0D red phosphorus quantum dots and DOX. The nanocomposite with DOX loading capacity (ca. 250 %) and photothermal conversion efficiency (ca. 54 %) showed both photothermal and photodynamic effects and a sensitive response of drug release to the acidic tumor microenvironment or NIR II laser irradiation. The nanocomposite exhibits good biosafety. Through the X-ray attenuation properties of bismuth, the nanocomposite serves as an excellent CT contrast agent, providing potential to perform CT-guided therapy.

To describe and analyze the status quo of cardiovascular clinical practice guidelines or expert consensuses including both Chinese medicine (CM) and integrative medicine, through systematic literatures searching and quality assessment. Data bases including Chinese Biomedical Literature Database, the China National Knowledge Infrastructure, Wanfang Data, China Science and Technology Journal Database were searched for published CM or integrative cardiovascular clinical practice guidelines or expert consensuses. The website www. medlive.cn was also retrieved as supplementary. The clinical practice evaluation tool AGREE II was used to assess the quality of included guidelines or consensuses. A total of 31 relevant clinical practice guidelines or expert consensuses were included, covering diagnosis, treatment, Chinese patent and patient fields. Common cardiovascular diseases like coronary heart diseases, heart failure and arrhythmia were also involved. Through analysis it was found that both the quantity and quality of included guidelines have been improved year by year. A total of 4 evidence-based clinical practice guideline has been found, one of which was a guideline project plan. Except that, the remaining 27 reports were all consensus-based guidelines. The scores of each field, from highest to lowest, were clarity of presentation (58%), scope and purpose (54%), stakeholder involvement (28%), rigor of development (21%), applicability (13%) and editorial independence (8%). Although clinical practice guidelines in cardiovascular domain of Chinese have gained increasing concern, with both quantity and quality improved, there is still huge gap in methodology and reporting standards between CM guidelines and international ones. On the one hand, it is essential to improve and standardize the methodology of developing CM guidelines. On the other hands, the evaluation system of evidence and recommendation with CM characters should be developed urgently.

Calcium ions (Ca2+) are extremely important for efficiently improving the mechanical properties of alginate dual-crosslinked hydrogels through the synergy of crack bridging of covalent crosslinking and hysteresis of ionic crosslinking, but it is hard to achieve a high content of Ca2+ (>5 wt%) in these hydrogels for the following reasons. The low solubility and poor dispersion of CaSO4 in the gelling solution lead to a low Ca2+ content (

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.

The substitution of noble metal platinum catalyst is one of the important research contents for sustainable development and is also the key to the practical application of photoelectrochemical (PEC) hydrogen production. In this work, we loaded the 1T-2H mixed phase MoS2 on the hydrogenated anatase/rutile heterophase TiO2 (A-H-RTNA) by hydrothermal method to prepare a new MoS2/A-H-RTNA electrode material. The prepared material exhibited higher carrier density, lower PL intensity and higher conductivity than Pt/A-H-RTNA because 1T-MoS2 has more active sites and lower charge transfer resistance than Pt. With the bias voltage of −0.4 V, the optimized 16MoS2/A-H-RTNA as photocathode shows the largest PEC hydrogen production rate of 1840 mmol m−2 h−1, which is 2.9 and 2.2 times higher than those of A-H-RTNA (625 mmol m−2 h−1) and Pt/A-H-RTNA (848 mmol m−2 h−1), respectively. We innovatively used the prepared 16MoS2/A-H-RTNA film as counter electrode instead of Pt electrode to construct a PEC system without any noble-metal. The result demonstrates that the noble-metal-free MoS2 loaded on TiO2 electrode as counter electrode has 75% PEC activity of noble metal Pt electrode. This study develops a PEC method for hydrogen evolution, which no longer depends on precious metal platinum as cathode.

Background N-of-1 trial is a desired and appropriate approach to assessing the efficacy and safety of traditional Chinese medicine (TCM) interventions. There have been an increasing number of N-of-1 trials for TCM published. However, a lack of preferred reporting guidance led in the general poor reporting quality of these trials. Due to the unique characteristics of TCM, the working group developed this CONSORT Extension for reporting N-of-1 Trials for Traditional Chinese Medicine (CENT for TCM) to assist TCM researchers in reporting N-of-1 trials for TCM. Methods We registered CENT for TCM at the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) Network (available at equator-network.org). The development was a comprehensive process through collection of the initial reporting items, two-round scientific Delphi consensus survey with 17 panelists, revision and formation of the final reporting checklist. Results The checklist includes 25 items within six domains, eight items in which were extended and elaborated on the items of the CENT 2015 checklist. Explanation of the items were listed adequately considering the nature of TCM, introducing the concept of TCM syndrome differentiation and TCM interventions. Conclusions CENT for TCM can be used to assess the completeness of the reporting of N-of-1 trials for TCM. The working group expect that CENT for TCM could be a practical tool to enhance the comprehensiveness and transparency of the design, implementation and reporting of N-of-1 trials for TCM.

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.

Understanding the chemical states and electronic states of superconducting materials can help researchers to grasp their superconducting mechanisms. Then, through doping, high pressure or other methods, the T c (Critical Temperature) can be boosted. Recently, a new layered carbide superconductor ThMo2Si2C was discovered. Its chemical states and electronic states are unknown. Here, the chemical states of ThMo2Si2C are investigated using X-ray photoelectron spectroscopy assisted with argon ion sputtering and Raman spectroscopy. The physical significance behind them is elucidated. Its electronic states are investigated by first-principles calculations. It is found that the major contribution to the total DOS (Density of States) is from Mo 4d state, which plays the dominant role in the superconductivity of ThMo2Si2C. The hybridization between Th 6d and Mo 4d is very weak. Thus, a separation of the structure into independent Mo-C-Si and Th subunits (layers) is justified from the point of view of electronic structure. A flat band along the A-M high-symmetry direction is observed near the Fermi level. The influence of the interlayer distance between Mo-C-Si units (layers) on the DOS and band structure is investigated by first-principles calculations too.

We systematically studied the magneto-resistance of strontium (Sr) doped topological insulator (TI) Bi[Formula: see text]Se[Formula: see text] films. For Bi[Formula: see text]Se[Formula: see text] films with relatively large classic magneto-resistance, we found that slightly Sr doping can completely suppress the classic magneto-resistance and make the weak antilocalization effect dominate in the weak-magnetic-field region. Consequently, the value of the magneto-resistance is enhanced by more than 2.7 times at 0.2 T in slightly doped samples. In contrast, in the strong-magnetic-field region, the magneto-resistance is strongly reduced by doping but exhibits linear magneto-resistance behavior. Our results suggest that the linear magneto-resistance behavior originates from the mobility fluctuation induced by disorder described by the Parish–Littlewood model. Our findings not only gain insights into the doping effect on the topological insulator but also provide an effective way to manipulate the magneto-transport properties of TI for potential applications in future.

By combining angle-resolved photoemission spectroscopy, scanning tunneling microscopy, atomic force microscope based piezoresponse force microscopy and first-principles calculations, we have studied the low-energy band structure, atomic structure, and charge polarization on the surface of a topological semimetal candidate TaNiTe_{5}. Dirac-like surface states were observed on the (010) surface by angle-resolved photoemission spectroscopy, consistent with the first-principles calculations. On the other hand, piezoresponse force microscopy reveals a switchable ferroelectriclike polarization on the same surface. We propose that the noncentrosymmetric surface relaxation observed by scanning tunneling microscopy could be the origin of the observed ferroelectriclike state in this novel material. Our findings provide a new platform with the coexistence of a ferroelectriclike surface charge distribution and novel surface states.

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.

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).

Clinical trial outcome reporting differs between studies integrating traditional Chinese medicine (TCM) and Western medicine, so that some clinical trials are not eligible for inclusion in a systematic review. The excluded studies are therefore less widely disseminated, and even valid studies are less likely to yield impact. This problem may be addressed by developing core outcome sets (COSs) for integrative medicine in specific healthcare areas. The first stage of development is to define the scope of the COS for integrative medicine, the second stage is to establish the need for such a COS, and the third stage is to develop a protocol and register the COS. The final stage involves three steps: (i) development of a comprehensive list of outcomes (including efficacy outcomes and safety outcomes and TCM syndromes) using systematic review, qualitative or cross-sectional research, and reviews of package inserts and medical records; (ii) merging and grouping of outcomes within domains; (iii) conducting two rounds of Delphi survey and consensus meetings with a range of stakeholders. The final COS will include a general COS and core TCM syndrome- set. Development of COSs for clinical trials of integrative medicine may help to standardize outcome reporting and reduce publication bias in the future.

To systematic review the effect of Chinese medicine (CM) on no or slow reflow after percutaneous coronary intervention (PCI) in myocardial infarction (MI) patients. The PubMed, EMBASE databases, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, China National Knowledge Infrastructure (CNKI), Chinese BioMedical Literature Database (CBM), Wanfang Knowledge Service Platform (Wanfang Database) and Chinese Scientific Journal Database (VIP) were searched up to December 2017. Randomized controlled trials (RCTs) which evaluated the effect of CM therapies on no or slow reflow after PCI in MI patients were included. The primary outcome was the effect of reperfusion. Secondary outcomes were left ventricular ejection fraction, incidence of major adverse cardiovascular events and adverse effect. Ten RCTs covering 814 patients were included. Two studies revealed that the incidence of no or slow reflow was less in Shenmai Injection (参麦注射液) group than in the control group measured by thrombolysis in myocardial infarction (TIMI) ⩽ 2 (risk ratio=0.55, 95% confidence interval 0.38 to 0.81, P=0.003, I2=37%). Two studies indicated that Salvianolate Injection showed no additional benefit on no or slow reflow measured by corrected TIMI frame count compared with the conventional treatment (mean difference −4.24, 95% confidence interval −13.03 to 4.54, P=0.34, I2=86%). In addition, Tongxinluo Capsules (通心络胶囊), Danhong Injection (丹红注射液) and Xuesaitong Injection (血塞通注射液) may have the potential to reduce no or slow reflow measured during or after PCI in individual studies. Current evidence from RCTs are not sufficient to evaluate the effect of CM adjuvant therapies on no or slow reflow after PCI for MI patients. The included studies are limited by small sample size and unclear baseline conditions. Further rigorously designed researches and verification studies with sufficient number of patients are warranted.

Tree peony (Paeonia section Moutan DC.) has recently been recognised as an important woody oil plant of high economic value, with its seeds containing high levels of α-linolenic acids (ALA,...

Objectives: Evaluating the quality of systematic reviews/meta-analysis of Wenxin granule in treating cardiac arrhythmia to provide evidence for clinical practice, and analyzing the problems in the research to identify potential research priorities for researchers. Method: The systematic reviews of Wenxin granule in treating cardiac arrhythmia were searched from 8 databases. The methodological quality and evidence quality were assessed by AMSTAR and GRADE respectively. Results: Nineteen eligible systematic reviews with 52,905 participants were included. The overall scores of AMSTAR ranged from 3 to 10 with a mean score of 6.5, the median score was 6. There were 9 (9/19, 47.37%) systematic reviews had the score of 7 or more. 6 of them with appropriate information were assessed the quality of evidence by GRADE. The results showed that the overall quality of evidence was limited (range from “very low” to “low”), no “moderate” or “high” quality of evidence existed. For the outcome reporting, no systematic reviews reported endpoints and limited evidence showed that there is causality between Wenxin granule and adverse effects/events. The outcome matrix showed that there are obvious heterogeneity and incompleteness for the outcome reporting in included systematic reviews, so that some included studies cannot be conducted meta-analysis. Meanwhile, there were studies excluded because of inappropriate outcome measures, such as outcome measures did not meet inclusion criteria, treatment time did not meet inclusion criteria, treatment time was unclear, incomplete data or the data cannot be extracted. Conclusions: Wenxin granule have limited efficacy and safety for treating arrhythmia. In the future, high quality of RCTs and systematic reviews should be conducted. Core outcome set for cardiac arrhythmia is needed to improve outcome reporting and decrease waste.

As one of the most common types of heart failure, the diagnosis and treatment of Ischemic heart failure are the main focus of clinic. In recent years, the studies on biomarkers have provided supports for clinical diagnosis, prognosis evaluation and stratification. The clinical application of new drugs and the development of non-drug treatment methods have brought more choices conventional treatment. At the same time, under the guidance of Traditional Chinese Medicine syndrome differentiation theory, Traditional Chinese Medicine therapy also plays an increasingly important role and shows its broad prospects

Tree peony has been widely planted as an excellent oil crop with high proportion of α-linolenic acid (ALA) in its seeds. It was reported that pollen sources have clear effects on fatty acid (FA) composition of its kernels. Nevertheless, the molecular basis of this novel phenomenon is poorly understood. In this study, four Paeonia suffruticosa cultivars whose pollen caused significant differences in ALA content of Paeonia rockii were selected as pollen donors and grouped under high and low ALA groups. After pollination, total FAs content, composition and expression profiles of 10 genes involved in the FA and triacylglycerol (TAG) biosynthetic pathways were investigated during seed development. During the rapid oil accumulation in seeds, three desaturase genes (SAD, FAD2, FAD3) showed much higher expression in high ALA group, and their differential expression profiles corresponded well with the variations in ALA content among different pollen sources. Overall, pollen sources could affect the expression level of genes associated with fatty acid modification and subsequently affect the composition of FA in the kernels.

Let p be a prime with $p\equiv1\bmod8$ , ψ be an eighth character modp, and $\tau(\psi)$ 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 $\tau(\psi)$ . In the end, we prove an interesting second-order linear recursive formula for it.

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 p p n the largest prime ≤ n and by P p n the smallest prime ≥ n , called as the Smarandache inferior prime part and superior prime part of n , respectively. Define I n ≔ 1 / n ∑ m ≤ n p p m and S n ≔ 1 / n ∑ m ≤ n P p m . In this short note, we proved some estimates on I n − S n and I n / S n , answering a question proposed by Kashihara and improving a result of Yan.

With the overall advancement of UHV AC and DC lines and the gradual development of large cross-regional power grids, the effective grounding of power equipment plays an important role in the safe and stable operation of the power system. Regarding the numerical uncertainty caused by the measurement of grounding grid parameters, this paper proposes a multi-dimensional safety evaluation method for grounding grids based on the gray correlation degree of interval numbers. First, construct an evaluation index system and use the coefficient of variation to determine the index weight, avoiding the subjectivity brought about by expert empowerment. Second, determine the evaluation level and construct an interval number evaluation matrix. Then, the kernel density estimation is used to fit the interval number evaluation value into a probability density distribution. Finally, the final evaluation results are gotten by evaluating the weighted JS divergence between the probability density distribution and the optimal distribution. Through an empirical analysis of a 220kV substation in Zhejiang, the effectiveness of the method is verified.

Lytic replication of Epstein-Barr virus (EBV) is not only essential for its cell–to–cell spread and host–to–host transmission, but it also contributes to EBV-induced oncogenesis. Thus, blocking EBV lytic replication could be a strategy for managing EBV-associated diseases. Previously, we identified a series of natural lignans isolated from the roots of Saururus chinensis (Asian lizard's tail) that efficiently block EBV lytic replication and virion production with low cytotoxicity. In this study, we attempted to elucidate the molecular mechanism by which these lignans inhibit EBV lytic replication. We found that a representative compound, CSC27 (manassantin B), inhibits EBV lytic replication by suppressing the expression of EBV immediate-early gene BZLF1 via disruption of AP-1 signal transduction. Further analysis revealed that manassantin B specifically blocks the mammalian target of rapamycin complex 2 (mTORC2)-mediated phosphorylation of AKT Ser/Thr protein kinase at Ser-473 and protein kinase Cα (PKCα) at Ser-657. Using phosphoinositide 3-kinase–AKT-specific inhibitors for kinase mapping and shRNA-mediated gene silencing, we validated that manassantin B abrogates EBV lytic replication by inhibiting mTORC2 activity and thereby blocking the mTORC2–PKC/AKT-signaling pathway. These results suggest that mTORC2 may have utility as an antiviral drug target against EBV infections and also reveal that manassantin B has potential therapeutic value for managing cancers that depend on mTORC2 signaling for survival.

Background: Development 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. Methods: A 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 a consensus meeting by video conference to vote. Results: Ninety-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 include 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), symptoms (clinical symptom score). Outcomes were recommended according to different types of disease. Outcome measurement instrument/definition were also recommended. Conclusion: Though there are some limitations for the research, such as insufficient patients and the public involvement, 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. Key words: COVID-19; core outcome set; traditional Chinese medicine; Western medicine; methodology.

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 were 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. Frontline clinicians, as well as nurse, methodologist, evidence based-medicine researcher, and staff from the Chinese Clinical Trials Registry participated 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 include 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), symptoms (clinical symptom score). Outcomes were recommended according to different types of disease. Outcome measurement instrument/definition were also recommended.ConclusionA COS for COVID-19 may improve consistency of outcome reporting in clinical trials.