[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.

[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.

[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.

Shuxuening Injection Inhibits Apoptosis and Reduces Myocardial Ischemia-Reperfusion Injury in Rats through PI3K/AKT Pathway.

OBJECTIVE: To investigate the main components and potential mechanism of Shuxuening Injection (SXNI) in the treatment of myocardial ischemia-reperfusion injury (MIRI) through network pharmacology and in vivo research. METHODS: The Traditional Chinese Medicine Systems Pharmacology (TCMSP) and PharmMapper databases were used to extract and evaluate the effective components of Ginkgo biloba leaves, the main component of SXNI. The Online Mendelian Inheritance in Man (OMIM) and GeneCards databases were searched for disease targets and obtain the drug target and disease target intersections. The active ingredient-target network was built using Cytoscape 3.9.1 software. The STRING database, Metascape online platform, and R language were used to obtain the key targets and signaling pathways of the anti-MIRI effects of SXNI. In order to verify the therapeutic effect of different concentrations of SXNI on MIRI in rats, 60 rats were first divided into 5 groups according to random number table method: the sham operation group, the model group, SXNI low-dose (3.68 mg/kg), medium-dose (7.35 mg/kg), and high-dose (14.7 mg/kg) groups, with 12 rats in each group. Then, another 60 rats were randomly divided into 5 groups: the sham operation group, the model group, SXNI group (14.7 mg/kg), SXNI+LY294002 group, and LY294002 group, with 12 rats in each group. The drug was then administered intraperitoneally at body weight for 14 days. The main biological processes were validated using in vivo testing. Evans blue/triphenyltetrazolium chloride (TTC) double staining, hematoxylin-eosin (HE) staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, enzyme-linked immunosorbent assay (ELISA), and Western blot analysis were used to investigate the efficacy and mechanism of SXNI in MIRI rats. RESULTS: Eleven core targets and 30 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were selected. Among these, the phosphoinositide 3-kinase (PI3K)/ protein kinase B (AKT) pathway was closely related to SXNI treatment of MIRI. In vivo experiments showed that SXNI reduced the myocardial infarction area in the model group, improved rat heart pathological damage, and reduced the cardiomyocyte apoptosis rate (all P<0.01). After SXNI treatment, the p-PI3K/PI3K and p-AKT/AKT ratios as well as B-cell lymphoma-2 (Bcl-2) protein expression in cardiomyocytes were increased, while the Bax and cleaved caspase 3 protein expression levels were decreased (all P<0.05). LY294002 partially reversed the protective effect of SXNI on MIRI. CONCLUSION: SXNI protects against MIRI by activating the PI3K/AKT signaling pathway.

[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.

[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.

[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.

[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.

Metabolic division of labor between Acetivibrio thermocellus DSM 1313 and Thermoanaerobacterium thermosaccharolyticum MJ1 enhanced hydrogen production from lignocellulose.

In this consortium, DSM 1313 was responsible for degrading lignocellulose by cellulosome, while the highly efficient hydrogen-producing bacterium MJ1 consumed the sugar produced by DSM 1313 to grow and produce more hydrogen. The results showed that the maximum hydrogen production of 259.57 mL/g substrate was obtained at the inoculation ratio (OD600) of 2:1 (DSM 1313:MJ1) and substrate concentration of 10 g/L, 70.84 % higher than pure culture. Furthermore, MJ1 dominated the co-culture system by using various sugars resulting from the biodegradation of substrate, thereby relieving the inhibition of sugar on DSM 1313 and leading to more hydrogen production. In the co-culture system, the value of extracellular oxidation-reduction potential and the ratio of NAD+/NADH was lower than that of pure culture. Additionally, at the gene level, [NiFe]-hydrogenase and [FeFe]-hydrogenase related enzymes were significantly up-regulated, leading to a two-fold increase in hydrogenase activity of co-culture compared with pure culture.

Enhanced bioelectricity generation in thermophilic microbial fuel cell with lignocellulose as an electron donor by resazurin-mediated electron transfer.

Microbial fuel cell (MFC) with lignocellulose as an electron donor is considered a sustainable biorefinery. However, low lignocellulose degradation and energy output restrict the scale of application. Herein, the extracellular electron transfer (EET) capacity of Acetivibrio thermocellus DSM 1313 with lignocellulose as substrate was shown to be mediated by the self-produced flavin, and its intracellular electron transfer went through the whole respiratory chain. Thermophilic MFC with resazurin exhibited an increase in the open circuit voltage by 37.78%, and a 2.60 folds increase in power density of 77.85 mW/m2, respectively. Differential pulse voltammetry and electrochemical impedance spectroscopy analysis indicated that resazurin decreased the solution and anode charge transfer resistance, and enhanced the extracellular electrochemical activity. Furthermore, resazurin resulted in a lower redox potential, allowing preferential electron transfer to resazurin rather than flavin. This research establishes a resazurin-mediated thermophilic MFC with lignocellulose as substrate, which provides novel idea on the biomass refinery.

Comparative genomic analysis reveals electron transfer pathways of Thermoanaerobacterium thermosaccharolyticum: Insights into thermophilic electroactive bacteria.

Microbial extracellular respiration is an important energy metabolism on earth, which is significant for the elemental biogeochemical cycle. Herein, extracellular Fe(III) and electrode respiration were confirmed in Thermoanaerobacterium thermosaccharolyticum MJ2. The intra/extracellular electron transfer (IET/EET) mechanism of MJ2 was investigated by comparative genomic analysis for the first time. Morphological characterization and electrochemical properties of anode illustrated that MJ2 generated bio-electricity by forming a biofilm. The respiration chain inhibition and enzyme activity tests showed that hydrogenase with cytochrome c (Cyt-c) was involved in IET of MJ2. Noteworthily, the exogenous Cyt-c increased hydrogenase activity to promote bio-electricity generation by 92.84 %. The Cyt-c gene synteny between MJ2 and another well-known exoelectrogen (Thermincola potens JR) indicated that Cyt-c bound to the outer membrane mediated the formation of biofilm involved in EET of MJ2. This study broadened the understanding of microbial extracellular respiration diversity and provided new insights to explore the electron transfer pathways of exoelectrogens.

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.

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.

Tobacco microbial screening and application in improving the quality of tobacco in different physical states.

The first-cured tobacco contains macromolecular substances with negative impacts on tobacco products quality, and must be aged and fermented to mitigate their effects on the tobacco products quality. However, the natural fermentation takes a longer cycle with large coverage area and low economic efficiency. Microbial fermentation is a method to improve tobacco quality. The change of chemical composition of tobacco during the fermentation is often correlated with shapes of tobacco. This study aimed to investigate the effects of tobacco microorganisms on the quality of different shapes of tobacco. Specifically, Bacillus subtilis B1 and Cytobacillus oceanisediminis C4 with high protease, amylase, and cellulase were isolated from the first-cured tobacco, followed by using them for solid-state fermentation of tobacco powder (TP) and tobacco leaves (TL). Results showed that strains B1 and C4 could significantly improve the sensory quality of TP, enabling it to outperform TL in overall texture and skeleton of tobacco products during cigarette smoking. Compared with the control, microbial fermentation could increase reducing sugar; regulate protein, starch, and cellulose, reduce nicotine, improve total aroma substances, and enable the surface of fermented TP and TL to be more loose, wrinkled, and porous. Microbial community analysis indicated that strains B1 and C4 could change the native structure of microbial community in TP and TL. LEfSe analysis revealed that the potential key biomarkers in TP and TL were Bacilli, Pseudonocardia, Pantoea, and Jeotgalicoccus, which may have cooperative effects with other microbial taxa in improving tobacco quality. This study provides a theoretical basis for improving tobacco fermentation process for better cigarettes quality.

[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.

[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.

A Data Mining-Based Study on Medication Rules of Chinese Herbs to Treat Heart Failure with Preserved Ejection Fraction.

OBJECTIVE: To summarize the medication rules of Chinese herbs to treat heart failure with preserved ejection fraction (HFPEF) based on data mining and to provide references for clinical utilization. METHODS: The China National Knowledge Infrastructure (CNKI), Wanfang database (Wanfang), VIP database (VIP), Chinese Biomedical Literature (CBM), PubMed, Embase, and Cochrane Library databases were searched from inception to October 2021 to identify relevant literature on treating HFPEF with Chinese herbs. Microsoft Excel 2019 was used to set up a database, and then, association rule analysis and hierarchical cluster analysis were performed by using apriori algorithm and hclust function respectively in R-Studio (Version 4.0.3). RESULTS: A total of 182 qualified papers were included, involving a total of 92 prescriptions, 130 Chinese herbs, and 872 individual herbs prescribed, with an average of 9.5 herbs per prescription. The six most frequently prescribed herbs were Astragali Radix (Huangqi), Salviae Miltiorrhizae Radix Et Rhizoma (Danshen), Poria (Fuling), Glycyrrhizae Radix Et Rhizoma (Gancao), Cinnamomi Ramulus (Guizhi), and Ginseng Radix Et Rhizoma (Renshen). There were 35 herbs used more than 5 times, involving 11 efficacy categories. The top three categories were deficiency-tonifying herbs, blood-activating and stasis-removing herbs, and dampness-draining diuretic herbs. The most commonly used herbs were mainly warm and sweet. The primary meridian tropisms were Lung Meridian, Heart Meridian and Spleen Meridian. Association rule analysis yielded 26 association rules, such as Astragali Radix (Huangqi) & Salviae Miltiorrhizae Radix Et Rhizoma (Danshen), Poria (Fuling), Cinnamomi Ramulus (Guizhi) & Atractylodis Macrocephalae Rhizoma (Baizhu). Hierarchical cluster analysis yielded four herb classes, and their functions were mainly qi-replenishing and yang-warming, blood-activating and diuresis-inducing. CONCLUSIONS: HFPEF is the syndrome of root vacuity and tip repletion, and its core pathogenesis is "deficiency", "stasis", and "water", with "deficiency" being the most principal, which is closely related to Xin (heart), Fei (Lung), and Pi (Spleen). The treatment of this disease occurs by improving qi, warming yang, activating blood and inducing diuresis. Astragali Radix (Huangqi) with Salviae Miltiorrhizae Radix Et Rhizoma (Danshen) is the basic combination of herbs applied.

Improved methane production with redox-active/conductive biochar amendment by establishing spatial ecological niche and mediating electron transfer.

The multifunctional roles of biochar as an additive in improving the performance of anaerobic digestion (AD) has not been perfectly understood. In this study, the effects of different biochars on AD and the enhanced mechanisms were explored. The CH4 productions were significantly improved with an increase of 45.9%, 28.3% and 16.5% by amendment with biochar pyrolyzed at 300℃ (BC300), 450℃ (BC450) and 600℃ (BC600), respectively. The tightly-bound communities were established on biochar at the initial stage of fermentation and functional microbes were selectively enriched/colonized in biochar-amended systems. Distinctive loosely-bound microbial communities were observed in BC300 and BC600 amended systems, among which electroactive Desulforhabdus and Clostridiales were the dominant bacteria. Biochar amendments also led to the formation of distinctive spatial ecological niches and the selection preference of microbes for specific spatial locations. These results provided new insights in revealing the potential mechanisms of enhanced AD performance by biochar amendment.

[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.