[Evidence map of clinical research on Chinese patent medicines for post-acute myocardial infarction heart failure].

An evidence map was established to comprehensively sort out the clinical research in the treatment of post-acute myocardial infarction heart failure(P-AMI-HF) with Chinese patent medicines, so as to reveal the distribution of evidence in this field. CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, and EMbase were searched for the randomized controlled trial(RCT), systematic reviews/Meta-analysis, and guidelines/consensus in this field. The evidence was analyzed and displayed in the form of a combination of text, charts, bubble charts, and bar charts, and the quality of RCT, systematic reviews/Meta-analysis, and guidelines/consensus were evaluated by RoB 1.0, AMSTAR2, and AGREE Ⅱ, respectively. A total of 163 RCTs, 4 systematic reviews/Meta-analysis, 1 network Meta-analysis, 2 observational studies, and 5 guidelines/consensus were included. In recent years, the total number of publications in this field has shown an upward trend. There were a variety of Chinese patent medicines in the treatment of P-AMI-HF, among which Shenfu Injection received the most attention. The clinical RCT and systematic reviews/Meta-analysis generally had poor quality, and the RCT mostly had a small size, a single center, and a short cycle. The outcome indicators mainly included cardiac function indicators, myocardial injury markers, total response rate, hemodynamic indicators, and safety indicators, while the characteristic efficacy indicators of TCM received insufficient attention. The development processes of some guidelines/consensus lack standardization, which compromised their authority and rationality. Chinese patent medicines have advantages in the treatment of P-AMI-HF, while there are also problems, which remain to be solved by more high-quality evidence. That is, more large-sample and multi-center clinical studies should be carried out in the future, and the formulation process of relevant systematic reviews/Meta-analysis and guideline/consensus should be standardized and the quality of evidence should be improved. In this way, the effectiveness and safety of Chinese patent medicines in the treatment of P-AMI-HF can be explored.

[Rules of prescriptions for heart failure of dilated cardiomyopathy based on latent structure model and association rules].

The latent structure model and association rules analysis were employed to explore the compatibility rules of prescriptions for heart failure of dilated cardiomyopathy, with a view to providing theoretical support for the clinical treatment of this disease based on syndrome differentiation and the formulation of guidelines. The articles about the treatment of heart failure of dilated cardiomyopathy were retrieved from CNKI, Wanfang, VIP, and SinoMed. The database was established in Microsoft Excel 2019. Lantern 5.0 and Rstudio were used to analyze the latent structure and association rules of Chinese medicine with the frequency greater than 4.00%. Furthermore, the frequency structure model was used to mine the rules of prescriptions for heart failure of dilated cardiomyopathy. The study included 175 traditional Chinese medicine(TCM) prescriptions, involving 128 Chinese medicines, with the cumulative frequency of 1 847. High-frequency medicines included Astragali Radix, Salviae Miltiorrhizae Radix et Rhizoma, Poria, Cinnamomi Ramulus, Glycyrrhizae Radix et Rhizoma, with the main effects of tonifying, activating blood, resolving stasis, and releasing exterior. A total of 17 hidden variables, 34 hidden categories, and 6 comprehensive cluster models, along with 15 core prescriptions, were obtained. According to the prescriptions, the patients mainly had the syndromes of heart-Yang and Qi deficiency, Qi deficiency and blood stasis, heart-kidney Yang deficiency or Qi-Yin deficiency. Fifty-four strong association rules were obtained through association rule analysis. The highest degree of support was observed for the combination of Salviae Miltiorrhizae Radix et Rhizoma-Astragali Radix, while the highest degree of confidence was found for the combination of Salviae Miltiorrhizae Radix et Rhizoma-Cinnamomi Ramulus-Ophiopogonis Radix-Astragali Radix. The heart failure of dilated cardiomyopathy, characterized by internal deficiency and excess manifestations, is attributed to deficiency, stasis, and water. These factors are closely associated with the heart, lung, and spleen. The treatment should follow the principle of invigorating Qi and warming Yang, and meanwhile the method of activating blood and resolve stasis or moving Qi and promoting urination can be adopted according to the specific syndrome of patients.

[Network Meta-analysis of Chinese patent medicine in treatment of heart failure with preserved ejection fraction].

This study systematically evaluated the efficacy and safety of different Chinese patent medicines combined with conventional western medicine in the treatment of heart failure with preserved ejection fraction(HFpEF) and ranked for the drug selection. Randomized controlled trial(RCT) on Chinese patent medicines in treatment of HFpEF were obtained from the CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, EMbase, Web of Science, and other databases from the inception to October 9, 2022. The included RCT was quantitatively analyzed using gemtc and rjags packages of R software for the network Meta-analysis. 74 RCTs were included, with a total of 7 192 patients enrolled, involving 11 different Chinese patent medicines(Shenfu Injection, Shenmai Injection, Qili Qiangxin Capsules, Shexiang Baoxin Pills, Xuezhikang Capsules, Salvia Miltiorrhiza Polyphenols Injection, Tanshinone Ⅱ_A Sulfonate Injection, Xinmailong Injection, Yangxinshi Tablets, Qishen Yiqi Dripping Pills, and Yixinshu Capsules). The results of network Meta-analysis are shown as followed.(1)In terms of improving clinical effective rate, for injection preparations, Xinmailong Injection + conventional western medicine was recommended. while for oral preparations, Shexiang Baoxin Pills + conventional western medicine, Qishen Yiqi Dripping Pills + conventional western medicine, and Qili Qiangxin Capsules + conventional western medicine were preferred.(2)In terms of improving the mitral ratio of peak early to late diastolic filling velocity(E/A), for injection preparations, Shenmai Injection + Salvia Miltiorrhiza Polyphenols Injection + conventional western medicine, Shenmai Injection + conventional western medicine, Shenfu Injection + conventional western medicine were preferred. While for oral preparations, Yixinshu Capsules + conventional western medicine was preferred.(3)In terms of reducing the ratio of early diastolic mitral inflow to early diastolic mitral annular velocity(E/e'), Shenfu Injection + conventional western medicine could be used as injection preparation, and Qili Qiangxin Capsules + conventional western medicine, Qishen Yiqi Dripping Pills + conventional western medicine for oral preparations.(4)In terms of improving 6-minute walking trail(6MWT), the injection preparations such as Shenmai Injection + conventional western medicine, Xinmailong Injection + conventional western medicine were suitable, while oral preparations like Qishen Yiqi Dripping Pills + conventional western medicine, Qili Qiangxin Capsules + conventional western medicine were recommended.(5)In terms of reducing N-terminal pro B-type natriuretic peptide(NT-proBNP), Qili Qiangxin Capsules + conventional western medicine were preferred.(6)In terms of reducing B-type natriuretic peptide(BNP), Xinmailong Injection + conventional western medicine could be used for injection preparation and Qili Qiangxin Capsules + conventional western medicine can be used for oral preparation. In terms of adverse drug reactions, there was no significant difference between Chinese patent medicine combined with conventional western conventional and traditional western medicine alone. The results showe that Chinese patent medicine combined with conventional western medicine in treating HFpEF is superior to conventional western medicine alone in reducing clinical symptoms, improving cardiac function, and improving exercise tolerance, which also has good drug safety. However, the existing evidence is still limited by the quality and quantity of included studies, so the above conclusion requires further validation through more prospective RCT.

[Network Meta-analysis of Chinese patent medicines in treatment of coronary heart disease complicated with heart failure].

The efficacy and safety of different Chinese patent medicines in the treatment of coronary heart disease complicated with heart failure were evaluated by network Meta-analysis. The randomized controlled trial(RCT) of Chinese patent medicines for coronary heart disease complicated with heart failure was retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, EMbase, and Cochrane Library with the time interval from inception to July 5, 2023. The quality of the included RCT was evaluated by the Cochrane's risk of bias assessment tool, and a network Meta-analysis was performed in Stata 16.0. Finally, a total of 82 RCTs were included, involving 9 298 patients and 11 Chinese patent medicines. Network Meta-analysis yielded the following results based on the surface under the cumulative ranking curve(SUCRA).(1)In terms of improving the clinical response rate, the top three interventions were Qishen Yiqi Dripping Pills + conventional western medicine, Zhenyuan Capsules + conventional western medicine, and Tongxinluo Capsules + conventional western medicine.(2) In terms of increasing left ventricular ejection fraction(LVEF), the top three interventions were Shexiang Baoxin Pills + conventional western medicine, Compound Danshen Dripping Pills + conventional western medicine, and Tongxinluo Capsules + conventional western medicine.(3) In terms of reducing left ventricular end-diastolic diameter(LVEDD), the top three interventions were Shexiang Tongxin Dripping Pills + conventional western medicine, Tongxinluo Capsules + conventional western medicine, and Shexiang Baoxin Pills + conventional western medicine.(4) In terms of reducing N-terminal pro-brain natriuretic peptide(NT-proBNP), the top three interventions were Shexiang Baoxin Pills + conventional western medicine, Qi-shen Yiqi Dripping Pills + conventional western medicine, and Compound Danshen Dripping Pills + conventional western medicine.(5) In terms of reducing hyper-sensitive C-reactive protein(hs-CRP), the top three interventions were Naoxintong Capsules + conventional western medicine, Shexiang Baoxin Pills + conventional western medicine, and Compound Danshen Dripping Pills + conventional western medicine.(6) In terms of increasing the distance of the six-minute walking trail(6MWT), the top three interventions were Zhen-yuan Capsules + conventional western medicine, Qili Qiangxin Capsules + conventional western medicine, and Qishen Yiqi Dripping Pills + conventional western medicine. The results showed that Chinese patent medicines combined with conventional western medicine can effectively improve the clinical response rate, LVEF, and 6MWT and reduce LVEDD, NT-proBNP, and hs-CRP. However, due to the overall low quality of the articles included and the few articles of some Chinese patent medicines, direct comparison between diffe-rent Chinese patent medicines remains to be carried out and the results need to be further verified.

Study on the effect of enzymatic treatment of tobacco on HnB cigarettes and microbial succession during fermentation.

Starch and cellulose are the fundamental components of tobacco, while their excessive content will affect the quality of tobacco. Enzymatic treatment with different enzymes is a promising method to modulate the chemical composition and improve the sensory quality of tobacco leaves. In this study, enzymatic treatments, such as amylase, cellulase, and their mixed enzymes, were used to improve tobacco quality, which could alter the content of total sugar, reducing sugar, starch, and cellulose in tobacco leaves. The amylase treatment changed surface structure of tobacco leaves, increased the content of neophytadiene in tobacco by 16.48%, and improved the total smoking score of heat-not-burn (HnB) cigarette products by 5.0 points compared with the control. The Bacillus, Rubrobacter, Brevundimonas, Methylobacterium, Stenotrophomonas, Acinetobacter, Pseudosagedia-chlorotica, and Sclerophora-peronella were found to be significant biomarkers in the fermentation process by LEfSe analysis. The Basidiomycota and Agaricomycetes were significantly correlated with aroma and flavor, taste, and total score of HnB. The results showed that microbial community succession occurred due to amylase treatment, which promoted the formation of aroma compounds, and regulated the chemical composition of tobacco, and improved tobacco quality during tobacco fermentation. This study provides a method for enzymatic treatment to upgrade the quality of tobacco raw materials, thereby improving the quality of HnB cigarettes, and the potential mechanism is also revealed by chemical composition and microbial community analysis. KEY POINTS: Enzymatic treatment can change the chemical composition of tobacco leaves. The microbial community was significantly affected by enzymatic treatment. The quality of HnB cigarettes was significantly improved by amylase treatment.

Enhancement of astaxanthin production from food waste by Phaffia rhodozyma screened by flow cytometry and feed application potential.

Astaxanthin is widely used in food, aquaculture, cosmetics, and pharmaceuticals due to its strong antioxidant activity and coloring ability, but its production from Phaffia rhodozyma remains the main challenge due to the high fermentation cost and low content of carotenoid. In this study, the production of carotenoids from food waste (FW) by a P. rhodozyma mutant was investigated. P. rhodozyma mutant screened by UV mutagenesis and flow cytometry could stably produce high carotenoids at 25°C, with carotenoid production (32.9 mg/L) and content (6.7 mg/g), respectively, increasing by 31.6% and 32.3% compared with 25 mg/L and 5.1 mg/g of wild strain. Interestingly, the carotenoid production reached 192.6 mg/L by feeding wet FW, which was 21% higher than batch culture. The 373 g vacuum freeze-dried products were obtained from the fermentation of 1 kg FW by P. rhodozyma, which contained 784 mg carotenoids and 111 mg astaxanthin. The protein, total amino acids, and essential amino acids content of the fermentation products were 36.6%, 40.5%, and 18.2% (w/w), respectively, and lysine-added fermentation products had the potential of high-quality protein feed source. This study provides insights for the high-throughput screening of mutants, astaxanthin production, and the development of the feed potential of FW.

[Research progress of histone acetylation in prevention and treatment of heart failure and new ideas based on traditional Chinese medicine].

Chronic heart failure(CHF) has become a worldwide public health problem due to its high morbidity and mortality, which seriously endangers people's lifespan and quality of life. In recent years, the treatment strategy of CHF has shifted its emphasis on short-term improvement and transformation of hemodynamics to long-term repair as well as improvement of the biological properties of heart failure. At present, with the continuous deepening of medical research, it has been found that histone acetylation is closely related to the occurrence and development of CHF. Traditional Chinese medicine, via regulating histone acetylation, delays ventricular remodeling, improves energy metabolism, inhibits fibrosis and cardiomyocyte hypertrophy, and intervenes in the development process of heart failure, thus reducing the mortality and the readmission rate and ultimately improving long-term prognosis. Therefore, this study reviewed the mechanism of histone acetylation in the treatment of heart failure as well as its prevention and treatment with traditional Chinese medicine, to provide reference for clinical treatment of CHF.

[Network Meta-analysis of efficacy and safety of different traditional Chinese medicine injections in treating post-acute myocardial infarction heart failure].

This study aims to systematically review the efficacy and safety of different traditional Chinese medicine injections combined with conventional treatment for patients with post-acute myocardial infarction heart failure. The relevant randomized controlled trial(RCT) was retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Cochrane Library with the time interval from inception to May 13, 2023. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. Network Meta-analysis was then performed in RevMan 5.3 and Stata 15.1. A total of 68 RCTs involving 11 traditional Chinese medicine injections and 5 995 patients were included. The results were explained based on the surface under the cumulative ranking curve(SUCRA).(1) In terms of reducing major adverse cardiovascular event(MACE), the therapies followed the trend of Xinmailong Injection+conventional treatment(83.8%) > Yiqi Fumai Injection+conventional treatment(57.1%) > Xuebijing Injection+conventional treatment(56.6%) > Shenmai Injection+conventional treatment(53.1%) > Shenfu Injection+conventional treatment(45.3%) > conventional treatment(4.0%).(2) In terms of increasing left ventricular ejection fraction(LVEF), the therapies followed the trend of Yiqi Fumai Injection+conventional treatment(84.0%) > Shenmai Injection+conventional treatment(69.6%) > Shenfu Injection+conventional treatment(62.7%) > Xinmailong Injection+conventional treatment(61.6%) > Shuxuening Injection+conventional treatment(54.8%) > Shenqi Fuzheng Injection+conventional treatment(46.7%) > Shengmai Injection+conventional treatment(45.9%) > Breviscapine Injection+conventional treatment(39.9%) > Danhong Injection+conventional treatment(38.8%) > Huangqi Injection+conventional treatment(38.7%) > conventional treatment(7.3%).(3) In terms of reducing B-type natriuretic peptide(BNP), the therapies followed the trend of Xinmailong Injection+conventional treatment(98.6%) > Shenmai Injection+conventional treatment(57.7%) > Shenfu Injection+conventional treatment(52.5%) > Shengmai Injection+conventional treatment(30.1%) > conventional treatment(11.0%).(4) In terms of reducing cardiac troponin Ⅰ(cTnⅠ), the therapies followed the trend of Shenmai Injection+conventional treatment(92.3%) > Yiqi Fumai Injection+conventional treatment(61.5%) > Shenfu Injection+conventional treatment(51.2%) > Shengmai Injection+conventional treatment(48.1%) > Xinmailong Injection+conventional treatment(26.6%) > conventional treatment(20.3%).(5) In terms of reducing high-sensitivity C-reactive protein(hs-CRP), the therapies followed the trend of Shenmai Injection+conventional treatment(79.9%) > Xinmailong Injection+conventional treatment(68.1%) > Shenfu Injection+conventional treatment(63.1%) > Xuebijing Injection+conventional treatment(56.7%) > Shengmai Injection+conventional treatment(51.1%) > Shenqi Fuzheng Injection+conventional treatment(42.8%) > Huangqi Injection+conventional treatment(34.7%) > conventional treatment(3.5%).(6) A total of 22 RCTs reported the occurrence of adverse reactions, mainly involving the damage of the circulatory system, digestive system, and coagulation function. The current evidence suggested that Xinmailong Injection+conventional treatment may have the best therapeutic effect in reducing MACE and BNP; Yiqi Fumai Injection+conventional treatment may be the best in increasing LVEF; Shenmai Injection+conventional treatment may be the best in reducing cTnI and hs-CRP. The safety needs further quantitative research and analysis. However, more high-quality RCT is required to validate the above conclusions due to limitations in the quality and quantity of the included studies.

[Outcome indicators in clinical trials on traditional Chinese medicine treatment of microvascular angina].

This study reviewed the current status of the use of outcome indicators in randomized controlled trial(RCT) on traditional Chinese medicine(TCM) treatment of microvascular angina(MVA) and analyzed the existing problems and possible solutions, aiming to provide a basis for the design of high-quality RCT and the establishment of core outcome sets for MVA. CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, Web of Science, and 2 clinical trial registries were searched for the RCT on TCM treatment of MVA according to pre-defined criteria. The Cochrane's risk of bias assessment tool was used to evaluate the methodological quality of the included RCT and the use of outcome indicators was summarized. A total of 69 RCTs were included, from which 100 outcome indicators were extracted, with the frequency of 430. The extracted outcome indicators belonged to 8 domains: response rate, symptoms and signs, physical and chemical examinations, TCM efficacy, safety, quality of life, economic evaluation, and long-term prognosis. The indicators of physical and chemical examinations were the most(70 indicators with the frequency of 211), followed by those of response rate(7 indicators with the frequency of 73) and symptoms and signs(7 indicators with the frequency of 54). The outcome indicators with higher frequency were adverse reactions, angina attack frequency, clinical efficacy, endothelin-1, total duration of treadmill exercise, and hypersensitive C-reactive protein. The RCT on TCM treatment of MVA had the following problems: irregular reporting of adverse reactions, diverse indicators with low frequency, lack of attention to the application of endpoint indicators, insufficient use of TCM differentiation and efficacy indicators, non-standard evaluation criteria and failure to reflect the basic characteristics of TCM. A unified MVA syndrome differentiation standard should be established, on the basis of which an MVA treatment efficacy evaluation system and core outcome indicator set that highlights the characteristics of TCM with patient-reported outcomes as the starting point should be established to improve the clinical research and research value.

[hiPSCs and organoids: prediction of arrhythmogenic risks for optimized traditional Chinese medicine].

Accurate assessment of the risks associated with traditional Chinese medicine(TCM), such as the potential to induce serious cardiovascular adverse reactions including cardiac arrhythmias, is crucial. This article introduced the pharmacological evaluation strategies for cardiac safety and the progress in cardiac organ research, with a focus on discussing the application prospects of human induced pluripotent stem cells(hiPSCs) and organoids in assessing the risks of TCM-induced cardiac arrhythmias. Compared with traditional animal models, hiPSCs and organoid models provide better reference and predictive capabilities, allowing for more accurate simulation of human cardiac responses. Researchers have successfully generated various cardiac tissue models that mimic the structure and function of the heart to evaluate the effects of TCM on the heart. The hiPSCs model, by reprogramming adult cells into pluripotent stem cells and differentiating them into cardiac cells, enables the generation of personalized cardiac tissue, which better reflects individual differences and drug responses. This provides guidance for the assessment of TCM cardiac toxicity risks. By combining organoid model with cardiac safety pharmacology strategies such as electrocardiogram monitoring and ion channel function assessment, the impact of TCM on the heart can be comprehensively evaluated. In addition, the application of the Comprehensive in Vitro Proarrhythmia Assay(CiPA) approach improves the accuracy of evaluation. Applying the CiPA approach to TCM research reveals potential risks and provides a scientific basis for the clinical application and industrial development of TCM. In conclusion, organoid model and cardiac safety pharmacology evaluation strategies provide important tools for assessing the cardiac toxicity risks of TCM. The combination of hiPSCs model, comprehensive assessment methods, and the CiPA strategy enables an accurate assessment of the risks of TCM-induced cardiac arrhythmias, thus providing a scientific basis for the safe use and international recognition of TCM in clinical practice. This contributes to ensuring the safety and efficacy of TCM and promoting its clinical application and global acceptance.

[Regularity of prescriptions for sick sinus syndrome based on latent structure combined with association rules].

This study aims to mine the regularity of traditional Chinese medicine(TCM) prescriptions for sick sinus syndrome(SSS) and provide a reference for clinical syndrome differentiation and treatment. The relevant papers were retrieved from CNKI, Wanfang, VIP, and SinoMed with the time interval from inception to January 31, 2023. The relevant information from qualified papers was extracted to establish a library. Lantern 5.0 and Rstudio were used to analyze the latent structure and association rules of TCMs with the frequency ≥3%, which combined with frequency descriptions, were used to explore the rules of TCM prescriptions for SSS. A total of 192 TCM prescriptions were included, involving 115 TCMs with the cumulative frequency of 1 816. High-frequency TCMs include Aconiti Lateralis Radix Praeparata, Ginseng Radix et Rhizoma, Glycyrrhizae Radix et Rhizoma, Astragali Radix, and Salviae Miltiorrhizae Radix et Rhizoma. The high-frequency medicines mainly had the effects of tonifying, releasing exterior with pungent-warm, and activating blood and resolving stasis. The analysis of the latent structure model yielded 13 hidden variables, 26 hidden classes, 8 comprehensive cluster models, and 21 core prescriptions. Accordingly, the common syndromes of SSS were inferred as heart-Yang Qi deficiency, heart-spleen Yang deficiency, heart-kidney Yang deficiency, Yang deficiency and blood stasis, both Qi and Yin deficiency and blood stasis, and Yin and Yang deficiency. The analysis of association rules predicted 30 strong association rules, among which Ginseng Radix et Rhizoma-Aconiti Lateralis Radix Praeparata had the highest support. SSS is a syndrome with Yang deficiency and Qi deficiency as the root causes and cold, phlegm, and stasis as the manifestations. The clinical treatment of SSS should focus on warming Yang and replenishing Qi, which should be supplemented with the therapies of activating blood and resolving stasis, warming interior and dissipating cold, or regulating Qi movement for resolving phlegm according to the patients' syndromes.

[Evidence mapping of clinical research on prevention and treatment of essential hypertension with Chinese patent medicines in recent six years].

In this study, the evidence mapping was employed to systematically analyze the clinical research literature and learn the distribution of evidence on the prevention and treatment of essential hypertension with Chinese patent medicines in recent six years. CNKI, Wanfang, VIP, SinoMed, PubMed, and Cochrane Library were searched for the relevant literature published from January 2016 to December 2021. The distribution characteristics of evidence were analyzed and presented in charts combined with words. A total of 263 studies were selected, including 238 intervention studies, 17 systematic reviews/Meta-analysis, and 8 observation studies. A total of 72 Chinese patent medicines were involved, among which Songling Xuemaikang Capsules had the highest frequency. In China, the attention to the treatment of essential hypertension with Chinese patent medicines was insufficient, as manifested by the declining number of published literature and the low quality of studies. There were cases of off-label use and medication without syndrome differentiation in clinical practice. Some outcome indicators failed to embody the characteristics of traditional Chinese medicine and there were cases ignoring the end-point outcome indicators. The overall quality of systematic reviews/Meta-analysis was low, and a variety of studies failed to draw valid conclusions. In the future, it is necessary to standardize the clinical medication and improve the quality of randomized controlled trial(RCT), so as to produce high-quality evidence-based medical evidence and provide strong support for the efficacy and safety of Chinese patent medicines in the prevention and treatment of essential hypertension.

[Medication rule of traditional Chinese medicine for heart failure after myocardial infarction: based on data mining].

This study aims to explore the medication rule of traditional Chinese medicine(TCM) for heart failure after myocardial infarction via data mining. To be specific, articles on the treatment of the disease with Chinese medicine were retrieved from CNKI, Wanfang, VIP, and SinoMed and related information was collected. A database was created with Microsoft Excel 2019, and SPSS Clementine 12.0 and IBM SPSS Statistics 23.0 were applied for association rules analysis, cluster analysis, and factor analysis. Finally, a total of 81 TCM prescriptions were screened out, involving 91 medicinals with cumulative use frequency of 740. The main syndromes were Qi deficiency and blood stasis, Yang Qi deficiency and blood stasis together with retained morbid fluid, deficiency of both Qi and Yin and blood stasis. The medicinals with high-frequency were Astragali Radix, Salviae Miltiorrhizae Radix et Rhizoma, Ginseng Radix et Rhizoma, Poria, and Aconiti Lateralis Radix Praeparata. The effects of the medicinals were tonifying deficiency, activating blood and resolving stasis, and promoting urination and draining dampness. The association rules analysis yielded "Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma" "Astragali Radix-Aconiti Lateralis Radix Praeparata-Salviae Miltiorrhizae Radix et Rhizoma" "Aconiti Lateralis Radix Praeparata-Ginseng Radix et Rhizoma-Salviae Miltiorrhizae Radix et Rhizoma-Astragali Radix" combinations. Cluster analysis yielded 6 basic formulas for heart failure after myocardial infarction. Factor analysis extracted a total of 8 common factors. Heart failure after myocardial infarction is characterized by the syndrome of deficiency in nature and excess in superficiality. The core pathogenesis is "deficiency" "stasis" "retained morbid fluid", particularly "deficiency". This disease is closely related to the heart, lung, and spleen. The basic treatment principle is replenishing Qi and activating blood, and warming Yang, excreting water, and nourishing yin should also be emphasized. The common basic prescriptions, such as Siwu Decoction, Shengmai Powder, Xuefu Zhuyu Decoction, Linggui Zhugan Decoction, and Shenfu Decoction, have been discovered. This study provided data for clinical medication and drug development for heart failure after myocardial infarction.

[Thoughts on path of R&D and registration of innovative traditional Chinese medicine with synchronous transformation of "series prescriptions"].

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 of " one prescription for single drug". This model refers to the R&D and registration system of modern drugs, and approximates to the " law-abiding" 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 to " 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 research". 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 of " one prescription for single drug" in the research and development of Chinese medicine. Additionally, a new type of " series prescriptions" 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.

Pretreatment of rice straw with recycled ionic liquids by phase-separation process for low-cost biorefinery.

An efficient ionic liquids (ILs) recycle technology will increase the economic viability of lignocellulosic biorefinery. The availability of recycling 1-butyl-3-methylimidazolium chloride for rice straw (RS) pretreatment was conducted. The kosmotropic salt K3 PO4 (TKP) solution was used as antisolvent for cellulose precipitation and forming a three-phase system consisting of biomass, ILs-rich, and salt-rich phases. The upper ILs phase and the bottom TKP phase were recycled without additional purification, which significantly simplifies the process for recovering ILs. Subsequently, the RS pretreated with multiple reusing ILs (RPRS) were investigated by components analysis, structure evolution, enzymatic hydrolysis, and fermentation experiments. The results showed that unpurified reusing ILs led to further delignification and improvement of enzyme accessibility of the pretreated RS. The reducing sugar yield of RS pretreated with 8th reusing IL (8th RPRS) could still reach 98.9%, and the ethanol and succinic acid concentrations achieved 91.9 and 29.3 g/L by simultaneous saccharification and cofermentation. The present study demonstrated that the ILs recovered by phase-separation process could be used for RS pretreatment, and achieving high titer ethanol fermentation.

Biotransformation of Phlorizin by Eurotium cristatum to Increase the Antioxidant and Antibacterial Activity of Docynia indica Leaves.

Docynia indica is used as a plant resource for both medicine and food in minority areas of southwestern China and Southeast of Asia, especially Docynia indica leaves, which are often used as a kind of functional tea in daily life. In our previous research, it has found that D. indica is rich in polyphenols (mainly phlorizin (PHZ)). Although PHZ is the first polyphenolic competitive inhibitor of sodium-dependent glucose transporters (SGLTs) to be discovered, the promotion and application of PHZ are limited due to its extremely low bioavailability. As a kind of aglycons, phloretin (PHT) possesses a better bioavailability and bioactivity than PHZ. Therefore, the conversion of PHZ to PHT in D. indica leaves by the method of biotransformation can be applied to solve the above issue. In this study, Aspergillus niger and Eurotium cristatum were used to transform PHZ to PHT in D. indica. Compared with Aspergillus niger, Eurotium cristatum can cause the equimolar conversion of PHZ to PHT. However, Aspergillus niger resulted in the complete degradation of PHZ. In the process of deep fermentation, PHZ in D. indica leaves was gradually biotransformed into PHT, and its content was as high as ~ 12% after fermentation. With the increase of PHT content, the antioxidant and antibacterial activity of Docynia indica leaves increased. By the acute toxicity evaluation, it was confirmed that Docynia indica leaves and Eurotium cristatum fermented leaves were much safer. These results indicate that Eurotium cristatum fermentation has the ability to transform the functional compounds in Docynia indica leaves and increase the antioxidant and antibacterial activity of Docynia indica, thus making it a substitute for PHT and functional tea.

[Meta-analysis of efficacy and safety of Xinmailong Injection in treatment of heart failure after acute myocardial infarction].

To systematically evaluate the clinical efficacy and safety of Xinmailong Injection in the treatment of heart failure after acute myocardial infarction. Seven Chinese and English databases, namely CNKI, VIP, Wanfang, SinoMed and PubMed, EMbase, Cochrane Library, were retrieved from the establishment of the database to March 2020. Randomized controlled trials for Xinmailong Injection in the treatment of heart failure after acute myocardial infarction were screened out. Cochrane collaboration network bias risk assessment tool was used to evaluate the literature quality of the studies included, and RevMan 5.3 software was used for Meta-analysis. A total of 926 relevant literatures were retrieved, and 12 studies were finally included, involving 972 patients, including 486 patients in the treatment group and 486 patients in the control group. The quality of the literatures included was generally low. The results of Meta-analysis showed that Xinmailong Injection combined with Western medicine could decrease the levels of BNP(SMD=-5.90, 95%CI[-8.45,-3.36], P<0.000 01) and NT-proBNP(SMD=-2.28, 95%CI[-3.13,-1.43], P<0.000 01) and decrease the levels of cTnI(SMD=-2.91, 95%CI[-4.21,-1.60], P<0.000 1), increase LVEF(MD=4.67, 95%CI[4.19, 5.16], P<0.000 01), increased 6 MWT(MD=73.90, 95%CI[67.51, 80.28], P<0.000 01], decreased LVEDD(MD=-5.46, 95%CI[-9.66,-1.25], P=0.01), reduce the level of serum inflammatory factor(hs-CRP, CRP, IL-6). In terms of safety, less adverse reactions occurred in the study, with no impact on the treatment. The results showed that clinical use of Xinmailong Injection combined with Western medicine in the treatment of heart failure after acute myocardial infarction can further alleviate clinical symptoms and relevant indexes, with less adverse reactions. However, due to the limitations in quantity and quality of the clinical studies included, the positive results can only be used as a hint and reference for clinical diagnosis and treatment, and more high-quality studies are needed to further confirm its efficacy.

[Key points of post-marketing evaluation of classic traditional Chinese medicine prescriptions based on combination of disease and syndrome].

Classic prescriptions, hospital preparations and famous traditional Chinese medicine(TCM) experience prescriptions are the main sources of new drug development and innovation. The multi-components and multi-targets treatment characteristics of TCM are advantages, but at the same time, broad indications, unclear clinical positioning and lack of evidence-based evidence support are the key problems affecting the play of TCM efficacy and restricting its promotion and application. The hot in recent research was to how to break through the bottleneck, precise clinical positioning, highlight the advantages of the classic TCM prescriptions, and complete the transformation from clinical practice, clinical research to clinical evidence, but at the same time, it is also the difficulty. The clinical research model of the combination of disease and syndrome can fully reflect the ancient medical case evidence of classic TCM prescriptions, the historical experience of human used and the characteristics of syndrome differentiation and treatment, and highlight the advantages of Chinese medicine. At the same time, under the modern disease classification system and research mode, is conducive to established the standardized clinical evidence report and evaluation system, is conducive to promote the integration of clinical research evidence, and avoids excessive attenuation of information. Based on the previous work of our team, the intention of this study was to make a comment about the key points of the post-marketing evaluation of the classic TCM prescriptions under the combination of disease and syndrome and includes key points:(1)With the syndrome as the carrier, connected with the classical prescription and clinical diseases, focused on the clinical positioning on macroscopically.(2)The combination of syndrome visualization, standardization and pharmacological molecular basis, focus on clinical precise positioning in microscopic.(3)Innovating therapeutic effect evaluation methods, reflecting the curative effect characteristics based on syndrome differentiation.(4)The combination of "randomized controlled evidence-based studies" and "real world evidence-based evaluation", focusing on clinical advantages, fully evidence-based evidence.(5)Make full use of clinical registration studies and pay attention to safety.

Reconstitution of cellulosome: Research progress and its application in biorefinery.

Lignocellulose, one of the most abundant renewable sources of sugar, can be converted into bioenergy through hydrolysis of cellulose and hemicellulose. Due to its renewability and availability in large quantities, bioenergy is considered as a possible alternative to fossil energy and attracts the attention of the world with increased concerns about environmental protection and energy crisis. The depolymerization of cellulosic substrate to monomer is the rate-limiting step in the bioconversion of lignocellulose by cellulolytic microbes. Cellulosome, a multienzyme complex from anaerobic cellulolytic bacteria, can efficiently degrade the cellulosic substrates. Previous studies have shown that the reconstitution of cellulosome in vitro and its heterologous expression or display on the cell surface can help to solve the low yield problem of cellulosome in cellulolytic bacteria. This paper reviews the research progress in the reconstitution of cellulosome as well as its application in biorefinery, including the construction of cellulosome as well as different methods for cellulosome reconstitution and its surface display. This review will promote the understanding of cellulosome and its reconstitution.

[Technical specifications for hospital-based intensive monitoring of post-marketing Chinese patent medicine].

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.