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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.

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.

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.

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,...

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.

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.

Background. Non-ST segment elevation acute coronary syndrome has been one of the most serious diseases threatening human health. Long-term cardiac rehabilitation and secondary prevention is the essential method to control the recurrence and mortality of the disease. Traditional Chinese medicine has proved the efficiency on the treatment of non-ST segment elevation acute coronary syndrome, but there is a lack of appropriate methodological design to reflect the characteristics of individualized diagnosis and treatment of it. Therefore, this study used the evidenced-based Goal Attainment Scale to evaluate the clinical effectiveness of traditional Chinese medicine on the treatment of non-ST segment elevation acute coronary syndrome. Method. This is observational research with the prospective feature. A total of 200 patients will be recruited and observed in the three months by telephone or door visit, collecting the individualized intervention of traditional Chinese medicine and evaluating through the method of evidence-based Goal Attainment Scale. Participants will be included according to the inclusion and exclusion criteria. Any reasons for loss to follow-up and adverse events will be recorded strictly. Discussion. The evidence-based Goal Attainment Scale provides a personalized method of evaluation based on the Goal Attainment Scale and combined with evidence-based medicine, which can better reflect the characteristics and superiority of individualized and dynamic intervention for traditional Chinese medicine on the long-term prevention and treatment of non-ST segment elevation acute coronary syndrome than other methods of design. It is of great significance to explore and promote this method of design in the future.

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.

Introduction. TCMI with the effect of Liqihuoxue and Yiqihuoxue has been applied as complementary therapies during the perioperative period of PCI for patients with ACS, while the recommended time points and plans of TCMI are still short of the support of evidence-based medicine. Methods. A systematic review and meta-analysis was conducted to evaluate the clinical efficacy and safety of TCMI on patients with ACS during the perioperative period of PCI. RCTs were searched based on standardized searching rules in seven medical databases from the inception up to August 2019. Two reviewers conducted the study selection, data extraction, and quality analysis independently. Data were analysed with the support of software RevMan and Stata. Results. A total of 68 articles with 6,043 patients were enrolled. The result of meta-analysis showed that the TCMI combined with western medicine was superior to the western medicine alone on clinical efficiency (before the PCI, before and after the PCI, or overall, P<0.05), the occurrence of MACE (myocardial infarction and stenocardia: before the PCI, before and after the PCI, or overall, P<0.05; arrhythmia: before and after the PCI, P<0.05), and the level of inflammatory factors (hs-CRP: before the PCI, before and after the PCI, or overall, P<0.05; IL-6: after the PCI, P<0.05). The TCMI with the effect of Liqihuoxue obtained more support compared with Yiqihuoxue based on the result of meta-analysis. Conclusions. TCMI with the effect of Liqihuoxue or Yiqihuoxue combined with western medicine generally showed the potential advantage on the treatment of ACS during the perioperative period of PCI. However, the optimal time point of intervention and recommended plan based on the effect still needs more clinical evidence. We consider that the research of precise and standardized application of TCMI will be a promising direction for TCM in the future.

Tree peony (Paeonia section Moutan DC.) species are woody oil crops with high unsaturated fatty acid content, including &alpha, linolenic acid (ALA/18:3, &gt, 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.

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.

(+)-Rutamarin inhibits EBV lytic DNA replication with an IC50 of 7.0 μM. (−)-Chalepin, a (−)-rutamarin derivative, was isolated from the whole plant of Ruta graveolens and used as a precursor of (−)-rutamarin. Altogether, 28 (−)-rutamarin derivatives were synthesized starting from (−)-chalepin. Of these, 16 compounds (2a–e, 3b–e, 3g, 4f, 4k, 4m–p) were found to be more potent against EBV lytic DNA replication than (−)-chalepin. Compounds 4m, 4n, and 4p exhibited IC50 values of 1.5, 0.32, and 0.83 μM and showed selectivity index values (SI) of 801, 211, and >120, respectively. Thus, compounds 4m, 4n, and 4p are considered promising leads for further laboratory investigation.

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: Gastric cancer has been the second cause of cancer death worldwide. Chemical comprehensive treatment programs primarily were the main therapy method with modest efficacy to gastric cancer. Traditional Chinese medicine (TCM) has been reported to alleviate adverse events induced by chemotherapy, but has not yet developed clinical trials to test and needs scientific evidence for making policy. Single-patient (N-of-1) trials might be an eligible study design for TCM since it well represented the individualized treatment philosophy of TCM. The aim of this study is to obtain information necessary to design a more series trial. METHODS: Individuals who underwent gastrectomy were included. Each patient suffered 3-week standard chemotherapy and 3-day treatment periods (decoction with Astragalus mongholicus and Semen Cuscutae or placebo: decoction without Astragalus mongholicus and Semen Cuscutae). Each trial lasted up to a maximum of 30 weeks or a minimum of 20 weeks. Staffs and participants were blinded to the randomization. This study was approved by Ethics Committee of First Hospital, Lanzhou University in November, 2014. RESULTS: From August, 2014 to March, 2015, 6 participants were included. There were 16 cycles compared between intervention and control decoction (2.28, 95% CI: 1.24–5.47), P