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Advanced glycation end products (AGEs) have been identified to transduce fibrogenic signals via inducing the activation of their receptor (RAGE)-mediated pathway. Recently, disrupting AGE-RAGE interaction has become a promising therapeutic strategy for chronic heart failure (CHF). Endothelial-to-mesenchymal transition (EndMT) is close to the cardiac fibrosis pathological process. Our previous studies have demonstrated that knockout RAGE suppressed the autophagy-mediated EndMT, and thus alleviated cardiac fibrosis. Plantamajoside (PMS) is the major bioactive compound of Plantago Asiatica, and its activity of anti-fibrosis has been documented in many reports. However, its effect on CHF and the underlying mechanism remains elusive. Thus, we tried to elucidate the protective role of PMS in CHF from the viewpoint of the AGEs/RAGE/autophagy/EndMT axis. Herein, PMS was found to attenuate cardiac fibrosis and dysfunction, suppress EndMT, reduce autophagy levels and serum levels of AGEs, yet did not affect the expression of RAGE in CHF mice. Mechanically, PMS possibly binds to the V-domain of RAGE, which is similar to the interaction between AGEs and RAGE. Importantly, this competitive binding disturbed AGEs-induced the RAGE-autophagy-EndMT pathway in vitro. Collectively, our results indicated that PMS might exert an anti-cardiac fibrosis effect by specifically binding RAGE to suppress the AGEs-activated RAGE/autophagy/EndMT pathway.

We report an electrocatalyst, Co bases (metallic Co and Co(OH)2) with fluoride-incorporated CoO coating on the surface of (CoO–F/Co), was synthesized by the electro-deposition method.

Human use experience(HUE) is important for the research and development of Chinese medicine. For the sake of more reliable data, the Professional Committee for Clinical Evaluation of Chinese Medicine of Chinese Pharmaceutical Association drafted the Expert Consensus on Human Use Experience Research of Traditional Chinese Medicine. It highlights that the research on HUE should have clear purposes, describe the theoretical basis of traditional Chinese medicine(TCM) for the clinical indications and prescriptions and the clinical value of prescriptions, especially the advantages or characteristics in clinical orientation and target population, evaluate the dosages and number of medicinals of prescriptions, verify the accordance with the preparation process of new Chinese medicine, analyze feasibility of the process for large-scale production and the rationality of the dosage form, and assess the medicinal material resources. Moreover, such research should have reasonable protocol and the collection of clinical data on HUE must comply with medical ethics and avoid conflicts of interest. The collection method should be selected depending on the characteristics of clinical data. Quality control measures should be formulated to ensure the authenticity, accuracy, completeness, reliability, and traceability of clinical data. The definitions on the clinical data should be uniform and clear, and methods should be adopted to avoid bias. The data can be statistically analyzed after the processing. Through the study of HUE, the clinical orientation, target population, commonly used dosage, course of treatment, preliminary efficacy and safety of Chinese medicine prescriptions will be clarified. On this basis, the data on the HUE should be discussed and conclusions will be drawn. Finally, a standardized report will be formed.

Traditional Chinese medicine(TCM) preparations in medical institutions are an important source of research and development(Ramp;D) of TCM new drug. With years of usage in therapy, these preparationsapos; safety and effectiveness have generally been validated in clinic. However, there are still a few disadvantages in TCM new medicine development, such as similar prescriptions, excessive prescription ingredients, too broad clinical orientation, lack of solid clinical data, issue in pharmaceutical quality control, and intellectual property disputes. Nowadays, the Three-Combined Evaluation System has strengthened policy support for the new TCM Ramp;D. In order to improve the success rate of TCM Ramp;D, due to the difficulties within, this paper proposes the process of transforming TCM preparations in medical institutions into new TCM and advocates the evaluation for druggability based on Human Use Experience(HUE). The potencial preparations ought to follow traditional Chinese Medical theory, sufficient HUE data in indication, syndrome type of TCM, target population, usage, dosage, and course of treatment are required. Particular attention should be paid to the source, evolution, and improvement process of prescription, and evaluate the dosage, ingredients, and herb resources of prescription. To assess the feasibility of mass production, it is necessary to determine whether the pharmaceutical process is mostly consistent with the new drug and whether the dosage form is reasonable. By summarizing the clinical application of the preparations, the whole picture of its clinical application would be reveal as much as possible. It is beneficial to evaluate its clinical value and Ramp;D prospect. In consideration of the lack of clinical safety data of preparations, safety profile needs to be collected according to the prescription. The quality of clinical data needs to be evaluated by focusing on the integrity and accuracy of data to reduce bias and confusion. Significant care should be paid to intellectual property protection to avoid legal disputes.

Application experience in humans, a summary of the clinical practice of traditional Chinese medicine(TCM), serves as an important data source for evaluating the safety, effectiveness, and clinical value of drugs in the development of new Chinese medicine. The collected data serving as the evaluation evidence through statistical analysis are critical to the research on the application experience in humans. This article summarized and analyzed the data characteristics and statistical methodology of application experience of Chinese medicine in humans, and concluded the data types, outcome evaluation, bias evaluation, confounding factors, and missing values. Furthermore, the article emphasized the importance of data analysis of application experience of Chinese medicine in humans for TCM evidence and put forward the current difficulties, such as low data quality and large internal bias, lack of individualized data processing methods, and lack of methods forquot;disease-syndrome combinationquot; data. We believe that with the development of methodology, the application experience of Chinese medicine in humans can strongly support the development of new drugs in TCM.

In recent years, the real-world studies (RWS) have attracted extensive attention, and the real-world evidence (RWE) has been accepted to support the drug development in China and abroad. However, there is still a lack of standards for the evaluation of the quality of RWE. It is necessary to formulate a quality evaluation and reporting specification for RWE especially in traditional Chinese medicine (TCM). To this end, under the guidance of China Association of Chinese Medicine, the Quality Evaluation and Reporting Specification for Real-World Evidence of Traditional Chinese Medicine (QUERST) Group, including 24 experts (clinical epidemiologists, clinicians, pharmacologists, ethical reviewer and statisticians), was established to develop the specification. This specification contains the listing of classification of RWS design and RWE, the general principles and methods of RWE quality evaluation (26 tools or scales), 25 types of bias in RWS, the special considerations in evaluating the quality of RWE of TCM, and the 19 reporting standards of RWE. This specification aims to propose the quality evaluation principles and key points of RWE, and provide guidance for the proper use of RWE in the development of TCM new drugs.

Since the implementation of drug registration in China, the classification of Chinese medicine has greatly met the needs of public health and effectively guided the transformation, inheritance, and innovation of research achievements on traditional Chinese medicine(TCM). In the past 30 years, the development of new Chinese medicine has followed the registration transformation model ofquot; one prescription for single drugquot;. This model refers to the Ramp;D and registration system of modern drugs, and approximates to thequot; law-abidingquot; medication method in TCM clinic, while it rarely reflects the sequential therapy of syndrome differentiation and comprehensive treatment with multiple measures. In 2017, Opinions on Deepening the Reform of Review and Approval System and Encouraging the Innovation of Drugs and Medical Devices released by the General Office of the CPC Central Committee and the General Office of the State Council pointed out that it is necessary toquot; establish and improve the registration and technical evaluation system in line with the characteristics of Chinese medicine, and handle the relationship between the traditional advantages of Chinese medicine and the requirements of modern drug researchquot;. Therefore, based on the development law and characteristics of TCM, clinical thinking should be highlighted in the current technical requirements and registration system of research and development of Chinese medicine. Based on the current situation of registration supervision of Chinese medicine and the modern drug research in China, the present study analyzed limitations and deficiency ofquot; one prescription for single drugquot; in the research and development of Chinese medicine. Additionally, a new type ofquot; series prescriptionsquot; was proposed, which was consistent with clinical thinking and clinical reality. This study is expected to contribute to the independent innovation and high-quality development of the TCM industry.

The development of traditional Chinese medicine(TCM) has always been highly valued and supported since 1949. However, Chinese medicine industry still faces great challenges in view of the current status of the industry and registration and approval of new products in recent years. Related policies also directly influence the development of the industry. The latest version of the Provisions for Drug Registration and Requirement on Registration Classification and Application Information of Traditional Chinese Medicines have been put into practice since 2020. Registration classification is the core content of the Chinese medicine registration management system, as it is closely related to the research, development, and registration of Chinese medicine and the innovative development of the industry. This article aims to systematically review the historical evolution of the category of Chinese medicine registration and analyze the current status and problems, which is expected to provide a reference for the formulation of supporting documents according to related laws and regulations.

Real world study(RWS) refers to the process of collecting real world data related to the health of research subjects in the real world environment for pre-set clinical problems and obtaining the status of drug use and potential benefits/risks through analysis. The data are derived from the hospital information system(HIS), medical insurance system, disease registration system, adverse drug reaction monitoring system, etc. Human use experience of traditional Chinese medicine(TCM) is a new concept put forward by experts after summarizing the problems existing in clinical trials of new TCM drugs. The data come partially from the real world, and more importantly, such key elements as the formulated prescriptions of new TCM drugs, principles and methods, and clinical applications should be covered. RWS is mainly used for adverse drug reaction monitoring after marketing, benefit evaluation of listed drugs, decision-making of medical treatment and medical insurance, as well as supervision and approval of special medical devices and special drugs. It is complementary to randomized controlled clinical trials. Human use experience is suitable for the research and development of Chinese medicinal compound preparations and the expansion of functions and indications. There are no special provisions for clinical indications and target population. There exists a sequential relationship between the human use experience and clinical trials. Specifi-cally, the summarization of human use experience provides good support for the design and implementation of clinical trials, which is an important segment in the research and development of new TCM drugs. The correlation between real-world data and research results and their reliability should be ensured in RWS, and the unreality should be avoided. The key to summarizing the human use experience is to identify the clinical orientation, target population, course of treatment, usage and dosage of new TCM drugs, and it should be noted that human use experience does not only mean clinical experience. Experimental clinical trial(PCT), a type of study in the real world, has been commonly employed for the summary of human use experience. RWS and human use experience are different research designs targeting different clinical questions in the research and development of new TCM drugs, which can be flexibly selected depending on the actual situation.

Cardiovascular diseases are the major cause of mortality in patients with advanced chronic kidney diseases. The predominant abnormality observed among this population is cardiac dysfunction secondary to myocardial remodelings, such as hypertrophy and fibrosis, emphasizing the need to develop potent therapies that maintain cardiac function in patients with end-stage renal disease.To identify potential compounds and their targets as treatments for cardiorenal syndrome type 4 (CRS) using molecular phenotyping and in vivo/in vitro experiments.Gene expression was assessed using bioinformatics and verified in animal experiments using 5/6 nephrectomized mice (NPM). Based on this information, a molecular phenotyping strategy was pursued to screen potential compounds. Picrosirius red staining, wheat germ agglutinin staining, Echocardiography, immunofluorescence staining, and real-time quantitative PCR (qPCR) were utilized to evaluate the effects of compounds on CRS in vivo. Furthermore, qPCR, immunofluorescence staining and flow cytometry were applied to assess the effects of these compounds on macrophages/cardiac fibroblasts/cardiomyocytes. RNA-Seq analysis was performed to locate the targets of the selected compounds. Western blotting was performed to validate the targets and mechanisms. The reversibility of these effects was tested by overexpressing Osteopontin (OPN).OPN expression increased more remarkably in individuals with uremia-induced cardiac dysfunction than in other cardiomyopathies. Lobetyolin (LBT) was identified in the compound screen, and it improved cardiac dysfunction and suppressed remodeling in NPM mice. Additionally, OPN modulated the effect of LBT on cardiac dysfunction in vivo and in vitro. Further experiments revealed that LBT suppressed OPN expression via the phosphorylation of c-Jun N-terminal protein kinase (JNK) signaling pathway.LBT improved CRS by inhibiting OPN expression through the JNK pathway. This study is the first to describe a cardioprotective effect of LBT and provides new insights into CRS drug discovery.

Cardiorenal syndrome type 4 (CRS type 4), with high rates of morbidity and mortality, has become a social and economic problem worldwide over the last few decades. Zhen-Wu decoction, a traditional medicine used in East Asia, has been widely used in the treatment of cardiovascular disease and kidney disease, and has shown potential therapeutic effects for the clinical treatment of CRS type 4. However, the underlying mechanism has not been extensively explored.The purpose of this study was to investigate the effect and underlying mechanism of Zhen-Wu decoction on uremic cardiomyopathy, offering a potential target for clinical treatment of CRS type 4.Five/six nephrectomized mice were utilized for experiments in vivo. The cardioprotective effects of Zhen-Wu decoction were evaluated by echocardiography and tissue staining. RNA-Seq data were used to investigate the potential pharmacological mechanism. The prediction of targets and active components was based on our previous strategy. Subsequently, the protective effect of the selected compound was verified in experiments in vitro.Zhen-Wu decoction alleviated cardiac dysfunction and endothelial injury in 5/6 nephrectomized mice, and the mechanism may involve the inflammatory process and oxidative stress. The activation of the Nrf2 signaling pathway was predicted to be a potential target of Zhen-Wu decoction in protecting endothelial cells. Through our machine learning strategy, we found that lactiflorin as an ingredient in Zhen-Wu decoction, alleviates IS-induced endothelial cell injury by blocking Keap1 and activating Nrf2.The present study demonstrated that Zhen-Wu decoction and lactiflorin could protect endothelial cells against oxidative stress in mice after nephrectomy by activating the Nrf2 signaling pathway.

This article proposes that the research and development of new Chinese medicines should be based on the clinical values of traditional Chinese medicine(TCM), and expounds the multiple clinical values of new Chinese medicines such as therapeutic effects, adjuvant treatment effects, improvement of disease symptoms, improvement of quality of life, prevention of diseases, etc., so as to broaden the clinical indications of new Chinese medicines. It is pointed out that the clinical value of TCM determines the clinical efficacy evaluation method of new Chinese medicines, so as to construct a clinical evaluation system of new Chinese medicines with the characteristics of TCM. It is proposed that the clinical value of new Chinese medicines should be found under the guidance of TCM theo-ry and clinical practice, and the theoretical innovation of TCM should be emphasized. There is no difference in the clinical value of drugs, and the key is to meet the clinical needs of patients. The research and development of new Chinese medicines ignores the theoretical guidance of Chinese medicine, and relying solely on animal experiment data may lead to failure of clinical trials. Different from the individualized treatment of TCM clinical syndrome differentiation, summarizing the core pathogenesis of TCM is the basis for the development of new Chinese medicines. It is necessary to summarize the pathogenesis of the disease under the guidance of TCM theory and encourage the application of modern medical methods to clarify the diagnosis of the disease. In view of the characteristics of new Chinese medicine research and development, it is proposed that the supporting role of human experience should be emphasized, and the technical points of clinical trials of new syndrome-type Chinese medicines should be explained.The use of objective indicators for syndrome evaluation, the selection of appropriate scales, and the formulation of reasonable treatment courses are advocated. During the research and development of new Chinese medicines, it is not only necessary to pay attention to modern medical safety indicators, but also to observe the evolution of TCM syndromes and specific TCM symptoms.

The relevant laws and regulations of drug clinical trials were introduced in this paper. It is pointed out that with drug re-gulatory laws and technological advances, clinical trials have become an important link in the development of new drugs of traditional Chinese medicines(TCM). Clinical trials of new drugs of TCM must comply with the requirement ofquot;Good Clinical Practice for Trial on Medicinal Productsquot;. In view of the particularities of clinical trials of new drugs of TCM, China has established an ethical review system for clinical research in TCM and carried out ethical review and certification of TCM research. In order to guide the development of clinical trials of new drugs of TCM, relevant departments have promulgated a series of guidelines for clinical trials of it, and established a new review system and technical requirements for clinical trials. Since 1983, thequot;national clinical pharmacology basequot; has been established. At present, there are 96 drug clinical trial institutions and 32 phase I clinical research wards in TCM hospitals, which can meet the development of clinical trials of new drugs of TCM. In the long-term practice, the technical team has continued to grow and develop, the research experience and technical strength have been significantly improved, and a large number of experts have become the backbone of clinical research in Chinese medicine. It is pointed out that we should attach importance to risk and benefit assessment, human experience, select scientific, objective and appropriate effectiveness indexes, evaluate the efficacy of TCM syndromes, and encourage the use of electronic methods in clinical research of new drugs of TCM. Based on the analysis of clinical trials of TCM in recent five years, it is pointed out that the active degree of clinical trials of new drugs of TCM is not high, the innovation ability of it is insufficient and the ability and enthusiasm of all aspects need to be improved. It is of great significance to carry out clinical trials of new traditional Chinese medicines to upgrade the TCM industry and produce high-level evidence-based medicine evidences. The high quality development of TCM can be promoted by strengthening clinical trials of new drugs of TCM.

Sincequot;the implementation of good clinical practicequot;(GCP), especially after 2015, the overall quality of new drug cli-nical trials in China has made significant progress, but compared with developed countries, there are still some obvious quality problems in clinical trials in China. Clinical trials of new drugs of traditional Chinese medicine are an important part of clinical trials of new drugs in China. In addition to some common problems in all clinical trials, there are also some special quality problems. In terms of security data, such as the collection of human safety data is not standardized, the management and judgment of unexpected serious adverse reactions(SUSAR) were not professional and timely, the relationship between adverse events and trial drug was not fully judged by investigator, In terms of effective data, such as primary efficacy outcome of the scale cannot be traced, TCM syndrome data cannot meet the requirements ofquot;source dataquot; in the revised GCP and the quality of traditional Chinese medicine placebo is not high, in terms of overall quality system construction, the sponsors and research institutions have not established a quality assurance system that conforms to the characteristics of new drug research of traditional Chinese medicine, etc. The quality of clinical trials of new drugs of traditional Chinese medicine is based on the current GCP and ICH-GCP in China, we should also consider the characteristics of clinical trials of new traditional Chinese medicine drugs, and formulate targeted quality control measures according to the characteristics of these new drugs of traditional Chinese medicine, to improve the overall quality of clinical trials of new drugs of traditional Chinese medicine in China, which has important strategic significance for promoting the research and development of new drugs of traditional Chinese medicine in China.

At present, the issues regarding multi-center clinical trials of new drugs of traditional Chinese medicine(TCM) remain: the lack of agreement on the content and scope of the ethical review among the ethics committee members of the center and the participating units results in repeated review, which leads to a time-consuming ethical review process. Moreover, the review capabilities of the ethics committees of various research centers are uneven, which is not necessarily beneficial to the protection of subjects' rights and safety. In view of the existing problems, to improve the efficiency of ethical review of multi-center clinical trials of new drugs of TCM and avoid repeated reviews, the TCM Clinical Evaluation Professional Committee of Chinese Pharmaceutical Association organized experts to formulate thequot;Consensus on collaborative ethical review of multi-center clinical trials of new drugs of TCM(version 1.0)quot;(hereinafter referred to asquot;Consensusquot;). Thequot;Consensusquot; is formulated in accordance with the requirements of relevant documents such as but not limited toquot;the opinions on deepening the reform of the evaluation and approval system to encourage the innovation of pharmaceutical medical devicesquot;,quot;the regulations of ethical review of biomedical research involving human subjectsquot;. Thequot;Consensusquot; covers the scope of application, formulation principles, conditions for the ethics committee of the center, sharing of ethical review resources, scope and procedure of collaborative review, rights and obligations, etc. The aims of thequot;Consensusquot; is to preliminarily explore and establish a scientific and operable ethical review procedure. Additionally, on the basis of fully protecting the rights and interests of the subjects, a collaborative ethical review agreement needs to be signed to clarify the ethical review responsibilities of all parties, to avoid repeated review, and to improve the efficiency and quality of ethical review in multi-center clinical trials of new drugs of TCM.

Collecting and summarizing human use experience(HUE) data, forming high-quality data and evidences that can be used for evaluation are the key links of HUE research on traditional Chinese medicine(TCM). The collection, collation and summary of human experience data were discussed in this paper. It is pointed out that the collection of HUE should be focus on the source of prescription of new traditional Chinese medicines, and be summarized based on dialectical thinking, experience in medication, characte-ristics of prescription and clinical application. The collected contents include prescription, process, clinical location and applicable population, efficacy data and safety data, etc. The methods include interview, clinical data summary and data mining. When the data formed based on HUE information is used as drug registration information, it is necessary to ensure that the data source is legal and compliant, and the ownership of intellectual property is clear.Data sources should meet the requirements of medical ethics. To avoid conflict of interest, data analysis should be conducted by an independent third party. It is necessary to develop the quality control measures of HUE data to ensure the data traceability, integrity, consistency and accuracy, and avoid data bias.The data of HUE should include the key data such as accurate clinical location and applicable population, recognized clinical efficacy and safety.After the formation of HUE, the statistical analysis plan of empirical data of human use should be formulated. Through strict data processing, statistical analysis and clinical interpretation, HUE can be produced for evaluation.

Braconid parasitoids reared from Malussieversii and Malusdomestica trees in NW China infested by Agrilusmali Matsumura (Coleoptera, Buprestidae) are illustrated and discussed. Six species were found parasitising Agrilusmali in NW China, namely, Atanycolusivanowi (Kokujev) (Braconinae), Doryctesundulatus (Ratzeburg), Pareucorystesvarinervis Tobias, Polystenusrugosus Foerster, Spathiussinicus Chao, and Spathiusbrevicaudis Ratzeburg (Doryctinae). All listed species are newly recorded parasitoids of Agrilusmali. Pareucorystesvarinervis and Spathiusbrevicaudis are new records for the Chinese fauna, but Spathiusbrevicaudis has been recorded from Taiwan before. Both sexes of Spathiusbrevicaudis are redescribed here to allow inclusion in the recent revision of the Chinese Spathius species. An identification key to the six braconid parasitoids of Agrilusmali in NW China is provided.

Sclerodermus pupariae Yang et Yao (Hymenoptera: Bethylidae), a newly described ectoparasitoid, has been used as a biocontrol agent against several buprestid and cerambycid pests in China. Both winged and wingless female morphs of S. pupariae can find and parasitize hosts; however, winged parasitoids can disperse faster and further to new habitats and thus are more adapted to spatial and temporal changes in host densities than wingless morphs. In the present study, we determined the effects of photoperiod and associated light intensity on the parasitoid development time from egg to adult, the proportion of winged females, fecundity, and progeny sex ratio. Significantly more winged female parasitoid progeny were produced with long-day photoperiods and high light intensity compared to short day-photoperiods and low light intensity treatments. Photoperiod alone (regardless of light intensity) has significant impact on developmental time of parasitoid progeny. Light intensity, interacted with photoperiod, significantly affected the degree of phenotypic partitioning and development time, but light intensity and photoperiod did not significantly influence the parasitoid fecundity and sex ratio. These results are relevant to laboratory rearing of S. pupariae when the optimal light conditions are needed to produce winged female parasitoids.

Fifteen parasitoids of Massicus raddei (Blessig & Solsky) (Coleoptera, Cerambycidae) are revised. The host is a serious pest of Quercus liaotungensis Koidz. and Q. mongolica Fisch. ex Ledeb. in NE China. All the parasitoids were reared from larvae of M. raddei. Pseudocyanopterus gen. nov. raddeivorus sp. nov., a new braconid wasp is described, and Cyanopterus tricolor (Ivanov) and Eubazus (E.) pallipes are new records for the Chinese fauna. An identification key to the parasitoids of M. raddei in China is provided. Detailed photographs of the parasitoids are provided.

Numerous clinical studies reported the effectiveness of herbal formula WuShen (WS) in treating cardiovascular diseases, yet relevant basic research was rarely conducted.Twelve main bioactive compounds of WS decoction were identified using the ultra-performance liquid chromatography-LTQ-Orbitrap mass spectrometer. A total of 137 active compounds with 613 targets were predicted by network pharmacology; their bioinformatic annotation and human microarray data suggested that wounding healing, inflammatory response, and gap junction were potentially the major therapeutic modules. A rat model of post-myocardial infarction (MI) heart failure (HF) was used to study the effects of WS on cardiac function, adverse cardiac remodeling, and experimental arrhythmias. Rats treated with WS led to a significantly improved pump function and reduced susceptibility to both ventricular tachycardia and atrial fibrillation, and restricted adverse cardiac remodeling partly via inhibiting TGFβ1/SMADs mediated extracellular matrix deposition and Rac1/NOX2/CTGF/Connexin43 -involved gap junction remodeling.The present study highlights that WS can be applied to the treatment of heart failure and the upstream therapy for atrial fibrillation and ventricular tachycardia through its preventive effect on adverse cardiac remodeling.

Chronic heart failure(CHF), a serious and end stage of various heart diseases, is a common chronic cardiovascular disease in the 21 st century. Literature data show that the 5-year mortality rate of hospitalized patients with heart failure is as high as 50%. Nowadays, the development of drugs treating heart failure has become a hot spot, meanwhile, traditional Chinese medicine(TCM) has shown the advantages in the treatment of chronic heart failure. In this article, four stages to develop traditional Chinese medicine for chronic heart failure were proposed. Firstly, discuss and screen ideas and methods with regard to the development of TCM and its prescriptions based on clinical needs. Secondly, study the preparation process and quality control method by referring to the existing clinical background of TCM prescriptions and analyzing the chemical compositions and pharmacological action characteristics of each herb in the prescription. Then, design non-clinical evaluation programs and carry out researches on pharmacodynamics and toxicology by combining the experience of clinical use of TCM prescriptions and future clinical positioning, and gradually adjust and improve the programs during implementation. Finally, conduct clinical trial application(IND) by submitting registration application data which are base on the clinical drug experience, preclinical research pharmacy, main pharmacodynamics, safety test results of the prescription, clinical positioning, and reasonable clinical trial plan designed by the theory of TCM. After passing the IND technical review, the clinical trial study shall be officially launched to achieve the desired results and obtain effective Chinese patent medicines for heart failure treatment.

The analysis and utilization of clinical scientific research data is an effective means to promote the progress of diagnosis and treatment, and a key step in the development of medical sciences. During the epidemic of coronavirus disease 2019(COVID-19), how to transform the limited diagnostic data into clinical research resources has attracted much attention. Based on the low efficiency of data collection and extraction, the inconsistency of data analysis, the irregularity of data report and the high timeliness of data update during the epidemic, this paper briefly analyzed the background and reasons of data application under the current situation, and then discusses the problems and feasible solutions of clinical data applications under the epidemic situation and, more importantly, for future medical clinical research methods. We put forward several methodological suggestions: ① gradually improve the medical big data model and establish the national medical health data center; ② improve the scientific research literacy of medical staff and popularize the basic skills and knowledge of GCP; ③ promote a scientific, networked and shared data collection and management mode; ④ use the mixed research method and collective analysis to improve the efficiency of clinical data analysis; ⑤ pay attention to narration of the medical feelings and emphasize the humanistic data of clinical medicine. It is expected to promote the standardized and reasonable use of clinical scientific research data, the rigorous integration of expert opinions, and ultimately the development of big data for national health care.

Since its outbreak in December 2019, a series of clinical trials on coronavirus disease 2019 (COVID-19) have been registered or carried out. However, the significant heterogeneity and less critical outcomes of such trials may be leading to a waste of research resources. This study aimed to develop a core outcome set (COS) for clinical trials on COVID-19 in order to tackle the outcome issues. The study was conducted according to the Core Outcome Measures in Effectiveness Trials (COMET) Handbook: Version 1.0, a guideline for COS development. A research group was set up that included experts in respiratory and critical medicine, traditional Chinese medicine (TCM), evidence-based medicine, clinical pharmacology, and statistics, in addition to medical journal editors. Clinical trial registry websites (www.chictr.org.cn and clinicaltrials.gov) were searched to retrieve clinical trial protocols and outcomes in order to form an outcome pool. A total of 78 clinical trial protocols on COVID-19 were included and 259 outcomes were collected. After standardization, 132 outcomes were identified within seven different categories, of which 58 were selected to develop a preliminary outcome list for further consensus. After two rounds of Delphi survey and one consensus meeting, the most important outcomes for the different clinical classifications of COVID-19 were identified and determined to constitute the COS for clinical trials on COVID-19 (COS-COVID). The COS-COVID includes one outcome for the mild type (time to 2019 novel coronavirus (2019-nCoV) reverse transcription-polymerase chain reaction (RT-PCR) negativity), four outcomes for the ordinary type (length of hospital stay, composite events, score of clinical symptoms, and time to 2019-nCoV RT-PCR negativity), five outcomes for the severe type (composite events, length of hospital stay, arterial oxygen partial pressure (PaO2)/fraction of inspired oxygen (FiO2), duration of mechanical ventilation, and time to 2019-nCoV RT-PCR negativity), one outcome for critical type (all-cause mortality), and one outcome for rehabilitation period (pulmonary function). The COS-COVID is currently the most valuable and practical clinical outcome set for the evaluation of intervention effect, and is useful for evidence assessment and decision-making. With a deepening understanding of COVID-19 and application feedback, the COS-COVID should be continuously updated.

Asian longhorned beetle, Anoplophora glabripennis (Motschulsky), is a high-risk invasive forest pest worldwide. We surveyed Asian longhorned beetle parasitoid guilds and their seasonal abundance using field-deployed sentinel host logs infested with Asian longhorned beetle eggs or newly hatched (early-instar) larvae in three different sites of China (Beijing City, Shanghai City, and Jilin Province) from 2015 to 2018. Our survey detected 12 species of hymenopteran parasitoids (four Pteromalidae, three Braconidae, two Eupelmidae, one Eurytomidae, one Ichneumonidae, and one Bethylidae) attacking sentinel Asian longhorned beetle larvae or eggs deployed in these sites. Total parasitism by all the parasitoid species varied with different sites and across different years of the survey (averaging 7–16% in Beijing, 4–11% in Shanghai, and 0–0.2% in Jilin Province). In addition, the seasonal pattern of parasitism also differed among different sites, with parasitism peaking in July in the northern site (Beijing, 19%) and June in the southern site (Shanghai, 16%). Among all the parasitoid species recovered, Oxysychus sp. (Hymenoptera: Pteromalidae) was the most abundant parasitoid species in both Beijing and Shanghai (with 42–66% relative abundance and an average of 6% Asian longhorned beetle parasitism). The second most abundant species was Bracon planitibiae Yang, Cao et Gould (Hymenoptera: Braconidae), which accounted for 35% of the species collected and caused an average of 5% Asian longhorned beetle parasitism. Relevance of our findings to Asian longhorned beetle biocontrol is discussed.

Two parasitoids, Metapelma beijingense Yang (Hymenoptera, Eupelmidae) and Spathius ochus Nixon (Hymenoptera, Braconidae) are redescribed and illustrated. Both were reared from Coraebus cavifrons Descarpentries & Villiers (Coleoptera, Buprestidae) boring in Symplocos stellaris Brand (Symplocaceae). Metapelma beijingense is a solitary parasitoid with a parasitism rate of about 13.5% and S. ochus is a gregarious parasitoid with a parasitism rate of about 21.2%. A revised key to Oriental and Palaearctic species of Metapelma Westwood and a key to the species of the Spathius labdacus-group are provided.

Upflow anaerobic filter (UAF) with actual domestic wastewater were examined in this study. The Impacts of hydraulic retention time (HRT) on the performance of a UAF and a primary methanogen group were investigated at mesophilic conditions. The chemical oxygen demand (COD) removal rate was more than 75% after 28 days acclimation at 35℃ and HRT of 24 h. With a gradual decrease in the HRT, the COD removal rate first increased and then decreased. When the HRT was 5 h, the COD removal rate was the highest, with an average 81.71% and a maximum of 87.18%. When the HRT decreased to 2.5 h, the average COD removal rate decreased to 75.12%. The methane produced per unit mass of substrate consumed (CH

Two parasitoids, Metapelma beijingense Yang (Hymenoptera, Eupelmidae) and Spathius ochus Nixon (Hymenoptera, Braconidae) are redescribed and illustrated. Both were reared from Coraebus cavifrons Descarpentries & Villiers (Coleoptera, Buprestidae) boring in Symplocos stellaris Brand (Symplocaceae). Metapelma beijingense is a solitary parasitoid with a parasitism rate of about 13.5% and S. ochus is a gregarious parasitoid with a parasitism rate of about 21.2%. A revised key to Oriental and Palaearctic species of Metapelma Westwood and a key to the species of the Spathius labdacus-group are provided.

In 2013,China pharmaceutical regulatory department issued guiduance on postmarketing drug safety monitoring for industry. It aimed to encourage industry to carry out postmarketing drug safety monitoring including hospital-based intensive monitoring of postmarketing Chinese patent medicine. Subsequently,more and more such kind of studies have been performed all over China. However,in view of the current situation in this field,the development of hospital-based intensive monitoring of postmarketing Chinese patent medicine lacks standardization,such as unreasonable design,omission of reports about adverse drug reactions,inadequate process of quality control,non-standardized interpretation of adverse reactions,etc. Therefore,it is necessary to formulate relevant technical specifications to guide this area. The developing of this technical specification refered to the international post-marketing safety monitoring model and advanced design concepts and methods. We developed it under the guidance of relevant laws,regulations and technical documents in China. Meanwhile the characteristics of Chinese patent medicines and the real situation in this area were considered. The aim of this technical specification is to obtain the incidence,type,degree and clinical manifestation of adverse drug reactions of Chinese patent medicines,to find new risk signals of adverse reactions,to identify risk factors,and to provide a basis for the formulation of risk management and control plans. This specification has been approved by China association of Chinese medicine which is numbered T/CACM011-2016.

Two new species of egg parasitoids, Oobius saimaensis Yao and Mottern new species and Oobius fleischeri Yao and Duan new species (Hymenoptera: Encyrtidae), are described from eggs of Agrilus fleischeri Obenberger, 1925 (Coleoptera: Buprestidae). Agrilus fleischeri is a phloem-feeding woodborer of poplar (Populus Linnaeus; Salicaceae) in northeastern China. These two species can be distinguished morphologically as O. fleischeri has five tarsomeres and O. saimaensis has four tarsomeres. Although O. saimaensis is morphologically similar to its sympatric congener O. agrili Zhang and Hang, 2005, an important natural enemy of the invasive emerald ash borer, Agrilus planipennis Fairmaire, 1888, molecular phylogenetics and morphological data indicate that they are distinct species. Phylogenetic relationships among the new species and other closely related species are also inferred by using DNA sequence data from several ribosomal and mitochondrial genes. In addition, we expand the known distribution of Oobius primorskyensis Yao and Duan, 2016 to include South Korea.

A new species of Eulophinae,Pnigalio eriocraniaeLi & Yang,sp. n., is described and illustrated. This new species is a larval ectoparasitoid ofEriocrania semipurpurella alpinaXu (Lepidoptera, Eriocraniidae), a leaf miner in birch trees,Betulaspp. (Betulaceae), in Qinghai Province, northwest China. The biology of the new species and a key to the known species from China are provided.

Agrilus fleischeri Obenberger (Coleoptera: Buprestidae) is an emerging pest of poplar trees in northeast China, and is responsible for poplar mortality throughout its range. Its biology and natural enemies were studied at two field locations from 2013 to 2015 as well as via laboratory experiments. Life history of A. fleischeri was univoltine on exotic Populus nigra var. italica and overwintered as mature larvae in pupal chambers; however, was semivoltine on native Populus davidiana and overwintered as 2nd or 3rd instar larvae in Liaoning Province, China. Adults emerged from late May to mid-August with a peak in early June. Eggs were first discovered in early June and continued to late August. Larvae fed from mid-June to late September of univoltine or from mid-June to the next early September of semivoltine. The sex ratio of adult beetles was approximately 1:1 (M:F). Mean longevities of female and male adults were 34.87 ± 18.70 and 34.33 ± 18.10 days, respectively. Mean duration of egg stage was 12.83 ± 1.10 days and pupal duration 26.40 ± 1.32 days. Mortality in the field was mainly caused by parasitoids; however, pathogens, predators, and host tree resistance were also noted. The egg parasitoids, Oobius spp. attacked 48.0% and 6.48% of A. fleischeri eggs in P. nigra var. italica and P. davidiana , respectively. Polystenus rugosus and Paramblynotus sp. parasitized 0.71% and 52.17% of larvae in P. nigra var. italica respectively. Euderus fleischeri , Polystenus rugosus , and Spathius sp. were found in P. davidiana with parasitism rates of 7.63%, 4.83%, and 0.25% respectively.

Bracon planitibiae sp. nov. (Hymenoptera, Braconidae), a new species parasitizing first instar larvae of Asian longhorned beetle, Anoplophora glabripennis (Motschulsky), (Coleoptera: Cerambycidae), is described. Its host is a serious wood boring pest in China, North America and Europe, where it causes severe damages to plantations of Acer spp., Populus spp., Salix spp., Ulmus spp., and many other ornamental and forest tree species. We obtained a variety of parasitoid species by using Asian longhorned beetle–infested sentinel logs to attract natural parasitoids, of which B. planitibiae sp. nov. is one. Detailed photographs of the new species are provided.

The gregarious idiobiont ectoparasitoid, Sclerodermus pupariae Yang et Yao, is a natural enemy that parasitizes buprestid and cerambycid beetle larvae in China. In a recent laboratory study of mass–reared female parasitoids on larvae of the substitute host, Thyestilla gebleri, the subsequent offspring were widely released to control target pests. To develop cost–effective techniques for rearing parasitoids, and improve the parasitic efficiency of Sclerodermus pupariae, several parasitoid–host ratios have been investigated. However, the mechanism whereby increasing the density of inoculated female wasps on a host affects female parasitoid fitness (adult performance and progeny developmental duration) remains unclear. In the present study, we examined the influence of parasitoid density (one to eight female wasps per host) on the time to first attack, paralyzing time, pre–oviposition period and oviposition period of foundresses and developmental duration of offspring. We showed that the time to first attack, paralyzing time, pre–oviposition period and oviposition period of foundresses were significantly negatively associated with parasitoid density, but that developmental duration of progeny was only affected at the larval stage. An increase in the parasitoid density to more than three female wasps per host had no significant influence on the investigated parameters. Our results suggest that host nutrition was adequate, and intraspecific interaction enhanced the parasitic efficiency of wasps sharing a single host. Furthermore, it is known that a suitable parasitoid–host ratio can play an important role in promoting mutually beneficial behaviors which enhance adult performance.

To rapidly estimate pine sawyer, Monochamus alternatus Hope, population densities in forests, the vertical distributions of M. alternatus oviposition sites and larvae on infested Masson pines (Pinus massoniana Lamb.) were studied. Results showed that the number of oviposition sites on sections of trunks between 0 and 2 m above ground was significantly greater than on sections of trunk above 2 m, and the vertical distribution had a significant logarithmic relationship with trunk height. The larval number of M. alternatus on dead infested trees had a significant difference among heights of trunks. Sections on trunks at 2–4 m usually contained the largest number of M. alternatus larvae, while the number of larvae on trunks above 10 m declined significantly, as well as in the 1 m section of trunk at the base. The vertical distribution of M. alternatus larvae on dead infested pines showed a distinct parabolic relationship with trunk height. The number of oviposition sites of M. alternatus on infested Masson pine trunks revealed a significant exponential relationship with the diameter at breast height (DBH) of trees. A significant positive linear relationship also was observed between M. alternatus larval number and DBH on the host pine trees, as well as between the numbers of larvae and oviposition sites on an individual tree. The total number of larvae in an infested tree could be calculated easily using an established equation, through counting the number of oviposition sites at 3–4 m of trunk aboveground. This study developed a practical method for rapid estimation of M. alternatus populations.

To investigate natural enemies of emerald ash borer (EAB), Agrilus planipennis Fairmaire (Coleoptera: Buprestidae), in northeastern China, we conducted field surveys of ash (Fraxinus Linnaeus (Oleaceae)) trees in semi-natural forests and plantations at variable EAB densities from 2008 to 2013. Our surveys revealed a complex of natural enemies including eight hymenopteran parasitoids and two apparently parasitic Coleoptera, woodpeckers, and several undetermined mortality factors. Parasitoid complex abundance and its contribution to EAB mortality varied with the time of year, type of ash stands, and geographic regions. The egg parasitoid Oobius agrili Zhang and Huang (Hymenoptera: Encyrtidae) and the larval parasitoid Tetrastichus planipennisi Yang (Hymenoptera: Eulophidae) were frequently observed in Jilin, Liaoning, and Heilongjiang provinces and in Beijing, but not in Tianjin. Spathius agrili Yang (Hymenoptera: Braconidae), however, was more prevalent near Beijing and further south in Tianjin. Larvae of two species of apparently parasitic beetle, Tenerus Laporte (Coleoptera: Cleridae) species and Xenoglena quadrisignata Mannerheim (Coleoptera: Trogossitidae), were also recovered attacking overwintering EAB in Liaoning Province, with Tenerus species being a dominant mortality agent (~13%). Our findings support the need to consider the geographic origin of insect natural enemies for EAB biocontrol, as well as an expanded foreign exploration for EAB natural enemies throughout its native range in Asia.

Pressure overload has an important role in heart failure, inducing excessive autophagy in cardiac myocytes that is considered to be pathogenic. Resveratrol has been reported to improve cardiac dysfunction induced by pressure overload, but it has been unclear whether resveratrol ameliorates cardiac dysfunction by regulating autophagy. In this study, heart failure was induced in rats by constriction of the abdominal aorta. Four weeks after surgery, the rats with heart failure were randomized to treatment with resveratrol (8 mg · kg(-1) · d(-1) by intraperitoneal injection) for 28 days or to intraperitoneal injection of the vehicle (propylene glycol) alone. Echocardiography was performed to assess cardiac function. Expression of brain natriuretic peptide messenger RNA in the left ventricle was detected by real-time polymerase chain reaction, whereas expression of proteins associated with autophagy (beclin-1 and lamp-1) was detected by western blotting and immunohistochemistry. Furthermore, autophagic vacuoles were detected in the heart by transmission electron microscopy, and the myocardial ATP content was measured by the bioluminescence method. Treatment with resveratrol significantly improved cardiac dysfunction and reduced brain natriuretic peptide expression in rats with heart failure. Resveratrol down-regulated beclin-1 and lamp-1 expression and also inhibited the formation of autophagic vacuoles in failing hearts. Furthermore, resveratrol restored the myocardial ATP level and reduced phosphorylation of AMP-activated protein kinase at Thr172. These results suggest that resveratrol may inhibit autophagy through inactivation of AMP-activated protein kinase and restoration of ATP in heart failure induced by pressure overload. Accordingly, resveratrol may be beneficial for patients with hypertensive heart disease.

Objectives To investigate the safety and efficacy of Yangxinkang Tablets (养心康片) in patients with chronic heart failure (CHF) and syndrome of qi and yin deficiency, blood stasis, and water retention.

A new species of Eulophinae, Pnigalio eriocraniae Li & Yang, sp. n., is described and illustrated. This new species is a larval ectoparasitoid of Eriocrania semipurpurella alpina Xu (Lepidoptera, Eriocraniidae), a leaf miner in birch trees, Betula spp. (Betulaceae), in Qinghai Province, northwest China. The biology of the new species and a key to the known species from China are provided.

Anastatus orientalis Yang et Gibson(Hymenoptera : Eupelmidae) is the egg parasitoid of lantern-fly Lycorma delicatula. The natural parasitism showed that: (1)the highest parasitism rate of egg masses was 68.96% in Yantai Shandong; (2)the highest parasitism rate of eggs was 32.98% in Haidian Beijing; (3)the eggs of parasitoids hatched and emerged earliest in Yangling Shaanxi; emergence time of different populations in Yantai, Guangang Tianjin, Qinhuangdao Hebei and Haidian was similar; (4) the sex ratios were various among the populations ranging from 1.92 to 1.94; (5) parasitism rates of egg masses on Populus sp., Salix sp. and Toona sinensis were not significantly different, the highest parasitism rate of egg masses was 64.3% on T. sinensis, and the lowest rate was 27.4% on Ailanthus altissima; (6)parasitism rates of eggs on Populus sp., Salix sp., T. sinensis and A. altissima were not significantly different, about 30% averagely.

This study investigated the influence of corn straw application on soil microbial communities and the relationship between such communities and soil properties in black soil. The crop used in this study was maize (Zea mays L.). The five treatments consisted of applying a gradient (50, 100, 150, and 200%) of shattered corn straw residue to the soil. Soil samples were taken from May through September during the 2012 maize growing season. The microbial community structure was determined using phospholipid fatty acid (PLFA) analysis. Our results revealed that the application of corn straw influenced the soil properties and increased the soil organic carbon and total nitrogen. Applying corn straw to fields also influenced the variation in soil microbial biomass and community composition, which is consistent with the variations found in soil total nitrogen (TN) and soil respiration (SR). However, the soil carbon-to-nitrogen ratio had no effect on soil microbial communities. The abundance of PLFAs, TN, and SR was higher in C1.5 than those in other treatments, suggesting that the soil properties and soil microbial community composition were affected positively by the application of corn straw to black soil. A Principal Component Analysis indicated that soil microbial communities were different in the straw decomposition processes. Moreover, the soil microbial communities from C1.5 were significantly different from those of CK (p

A new species of CallimomoidesGirault 1926 (Hymenoptera: Pteromalidae), Callimomoides monochaphagae Yang, sp. n., is described from China. It is a solitary endoparasitoid of eggs of the pine sawyer, Monochamus alternatus Hope (Coleoptera: Cerambycidae), a serious pest that causes damage to pine trees native to China, particularly Pinus massoniana Lambert and Pinus tabulaeformis Carrière. Furthermore, M. alternatus is the main vector of the pine wood nematode, Bursaphelenchus xylophilus (Steiner&Buhrer) Nickle in China and other eastern Asian countries. C. monochaphagae has great potential as a biocontrol agent for suppression of the longhorned beetle because parasitism rates of 12.6% have been observed and this species has a relative high female:male sex ratio (1.86:1). Detailed photographs of the key characters of the new species are supplied. In addition, a key to the currently known species of Callimomoides throughout the world is provided. Type specimens are deposited in the Insect Museum, Chinese Academy of Forestry, Beijing, China.