Interplay of ferroptosis, cuproptosis, and PANoptosis in cancer treatment-induced cardiotoxicity: Mechanisms and therapeutic implications.

With the prolonged survival of individuals with cancer, the emergence of cardiovascular diseases (CVD) induced by cancer treatment has become a significant concern, ranking as the second leading cause of death among cancer survivors. This review explores three distinct types of programmed cell death (PCD): ferroptosis, cuproptosis, and PANoptosis, focusing on their roles in chemotherapy-induced cardiotoxicity. While ferroptosis and cuproptosis are triggered by excess iron and copper (Cu), PANoptosis is an inflammatory PCD with features of pyroptosis, apoptosis, and necroptosis. Recent studies reveal intricate connections among these PCD types, emphasizing the interplay between cuproptosis and ferroptosis. Notably, the role of intracellular Cu in promoting ferroptosis through GPX4 is highlighted. Additionally, ROS-induced PANoptosis is influenced by ferroptosis and cuproptosis, suggesting a complex interrelationship. This review provides insights into the molecular mechanisms of these PCD modalities and their distinct contributions to chemotherapy-induced cardiotoxicity. Furthermore, we discuss the potential application of cardioprotective drugs in managing these PCD types. This comprehensive analysis aims to advance the understanding, diagnosis, and therapeutic strategies for cardiotoxicity associated with cancer treatment.

Botanical drugs: a new strategy for structure-based target prediction.

Target identification of small molecules is an important and still changeling work in the area of drug discovery, especially for botanical drug development. Indistinct understanding of the relationships of ligand-protein interactions is one of the main obstacles for drug repurposing and identification of off-targets. In this study, we collected 9063 crystal structures of ligand-binding proteins released from January, 1995 to April, 2021 in PDB bank, and split the complexes into 5133 interaction pairs of ligand atoms and protein fragments (covalently linked three heavy atoms) with interatomic distance ≤5 Å. The interaction pairs were grouped into ligand atoms with the same SYBYL atom type surrounding each type of protein fragment, which were further clustered via Bayesian Gaussian Mixture Model (BGMM). Gaussian distributions with ligand atoms ≥20 were identified as significant interaction patterns. Reliability of the significant interaction patterns was validated by comparing the difference of number of significant interaction patterns between the docked poses with higher and lower similarity to the native crystal structures. Fifty-one candidate targets of brucine, strychnine and icajine involved in Semen Strychni (Mǎ Qián Zǐ) and eight candidate targets of astragaloside-IV, formononetin and calycosin-7-glucoside involved in Astragalus (Huáng Qí) were predicted by the significant interaction patterns, in combination with docking, which were consistent with the therapeutic effects of Semen Strychni and Astragalus for cancer and chronic pain. The new strategy in this study improves the accuracy of target identification for small molecules, which will facilitate discovery of botanical drugs.

ResNet18DNN: prediction approach of drug-induced liver injury by deep neural network with ResNet18.

Drug-induced liver injury (DILI) has always been the focus of clinicians and drug researchers. How to improve the performance of the DILI prediction model to accurately predict liver injury was an urgent problem for researchers in the field of medical research. In order to solve this scientific problem, this research collected a comprehensive and accurate dataset of DILI with high recognition and high quality based on clinically confirmed DILI compound datasets, including 1446 chemical compounds. Then, the residual neural network with 18-layer by using more 5-layer blocks (ResNet18) with deep neural network (ResNet18DNN) model was proposed to predict DILI, which was an improved model for DILI prediction through vectorization of compound structure image. In predicting DILI, the ResNet18DNN learned greatly and outperformed the existing state-of-the-art DILI predictors. The results of DILI prediction model based on ResNet18DNN showed that the AUC (area under the curve), accuracy, recall, precision, F1-score and specificity of the training set were 0.973, 0.992, 0.995, 0.994, 0.995 and 0.975; those of test set were, respectively, 0.958, 0.976, 0.935, 0.947, 0.926 and 0.913, which were better than the performance of previously published described DILI prediction models. This method adopted ResNet18 embedding method to vectorize molecular structure images and the evaluation indicators of Resnet18DNN were obtained after 10 000 iterations. This prediction approach will greatly improve the performance of the predictive model of DILI and provide an accurate and precise early warning method for DILI in drug development and clinical medication.

The prediction approach of drug-induced liver injury: response to the issues of reproducible science of artificial intelligence in real-world applications.

In the previous study, we developed the generalized drug-induced liver injury (DILI) prediction model-ResNet18DNN to predict DILI based on multi-source combined DILI dataset and achieved better performance than that of previously published described DILI prediction models. Recently, we were honored to receive the invitation from the editor to response the Letter to Editor by Liu Zhichao, et al. We were glad that our research has attracted the attention of Liu's team and they has put forward their opinions on our research. In this response to Letter to the Editor, we will respond to these comments.

[Current landscape and emerging trends in academic development of traditional Chinese medicine in new era].

The discipline development is the pillar for the development of traditional Chinese medicine( TCM). The academic progress in TCM is the commanding height of the discipline development of TCM. To lead and promote the development and academic progress of TCM, the China Association of Chinese Medicine has summarized the Top Ten Academic Achievements in Traditional Chinese Medicine during 2020-2022, the Major Scientific Problems, Engineering Technical Problems, and Industrial Technical Problems in Traditional Chinese Medicine during 2019-2023, and the Remarkable Research Achievements of Traditional Chinese Medicine during 2012-2022. Based on the above research reports and the research achievements awarded the national science and technology prizes in TCM in the last 20 years and according to the current situation and layout of TCM discipline development, this paper reviews the major research achievements of TCM in the last two decades and the latest research progress in TCM during 2020-2023. The major scientific, engineering technical, and industrial technical problems in TCM are analyzed and the emerging trends of TCM are prospected in accordance with the development laws and characteristics of TCM. This review provides new ideas and reference for the high-quality development of TCM in the new era.

Advances in the application of nanotechnology in reducing cardiotoxicity induced by cancer chemotherapy.

Advances in the development of anti-tumour drugs and related technologies have resulted in a significant increase in the number of cancer survivors. However, the incidence of chemotherapy-induced cardiotoxicity (CIC) has been rising continuously, threatening their long-term survival. The integration of nanotechnology and biomedicine has brought about an unprecedented technological revolution and has promoted the progress of anti-tumour therapy. In this review, we summarised the possible mechanisms of CIC, evaluated the role of nanoparticles (including liposomes, polymeric micelles, dendrimers, and hydrogels) as drug carriers in preventing cardiotoxicity and proposed five advantages of nanotechnology in reducing cardiotoxicity: Liposomes cannot easily penetrate the heart's endothelial barrier; optimized delivery strategies reduce distribution in important organs, such as the heart; targeting the tumour microenvironment and niche; stimulus-responsive polymer nano-drug carriers rapidly iterate; better economic benefits were obtained. Nanoparticles can effectively deliver chemotherapeutic drugs to tumour tissues, while reducing the toxicity to heart tissues, and break through the dilemma of existing chemotherapy to a certain extent. It is important to explore the interactions between the physicochemical properties of nanoparticles and optimize the highly specific tumour targeting strategy in the future.

[Pharmacological research progress of five classical prescriptions in treatment of chronic heart failure].

Chronic heart failure(CHF) is a comprehensive clinical syndrome caused by multiple factors that result in structural and/or functional abnormalities of the heart, leading to impaired ventricular contraction and/or relaxation functions. This medical condition represents the final stage of various cardiovascular diseases. In the treatment of CHF, multiple clinical studies have demonstrated the benefits of using traditional Chinese medicine(TCM) to control oxidative stress, inflammation, and apoptosis, thereby delaying ventricular remodeling and reducing myocardial fibrosis. In this study, common TCM syndromes in the diagnosis and treatment of CHF in recent years were reviewed and summarized. Five common treatment methods including benefiting Qi and activating blood circulation, enhancing Qi and nourishing Yin, warming Yang for diuresis, eliminating phlegm and dampness, rescuing from collapse by restoring Yang, and corresponding classic prescriptions in prevention and treatment of CHF were concluded under the guidance of TCM syndrome differentiation thinking. Meanwhile, research progress on the modern pharmacological effects of these classic prescriptions was systematically discussed, so as to establish a unique treatment system for CHF by classic prescriptions under the guidance of TCM syndrome differentiation theory and provide innovative diagnosis and treatment strategies for clinical CHF.

[Advances in animal models of chronic heart failure and its applications in traditional Chinese medicine].

Chronic heart failure(CHF) is a series of clinical syndromes in which various heart diseases progress to their end stage. Its morbidity and mortality are increasing year by year, which seriously threatens people's life and health. The diseases causing CHF are complex and varied, such as coronary heart disease, hypertension, diabetes, cardiomyopathy and so on. It is of great significance to establish animal models of CHF according to different etiologies to explore the pathogenesis of CHF and develop drugs to prevent and treat CHF induced by different diseases. Therefore, based on the classification of the etiology of CHF, this paper summarizes the animal models of CHF widely used in recent 10 years, and the application of these animal models in traditional Chinese medicine(TCM) research, in order to provide ideas and strategies for studying the pathogenesis and treatment of CHF, and provide ideas for TCM modernization research.

Immunometabolism at the service of traditional Chinese medicine.

To enhance therapeutic efficacy and reduce adverse effects, ancient practitioners of traditional Chinese medicine (TCM) prescribe combinations of plant species/animal species and minerals designated "TCM formulae" developed based on TCM theory and clinical experience. TCM formulae have been shown to exert curative effects on complex diseases via immune regulation but the underlying mechanisms remain unknown at present. Considerable progress in the field of immunometabolism, referring to alterations in the intracellular metabolism of immune cells that regulate their function, has been made over the past decade. The core context of immunometabolism is regulation of the allocation of metabolic resources supporting host defense and survival, which provides a critical additional dimension and emerging insights into how the immune system and metabolism influence each other during disease progression. This review summarizes research findings on the significant association between the immune function and metabolic remodeling in health and disease as well as the therapeutic modulatory effects of TCM formulae on immunometabolism. Progressive elucidation of the immunometabolic mechanisms involved during the course of TCM treatment continues to aid in the identification of novel potential targets against pathogenicity. In this report, we have provided a comprehensive overview of the benefits of TCM based on regulation of immunometabolism that are potentially applicable for the treatment of modern diseases.

Seco and Nor-seco Isodhilarane-Type Meroterpenoids from Penicillium purpurogenum and the Configuration Revisions of Related Compounds.

Seco and nor-seco isodhilarane-type meroterpenoids (SIMs and NSIMs) are mainly found in Penicillium fungi and have been characterized by highly congested polycyclic skeletons and a broad range of bioactivities. However, the literature reports inconsistent configuration assignments for some SIMs and NSIMs, due to their complex polycyclic systems and multichiral centers. Herein, we described eight SIMs and NSIMs isolated from the EtOAc extract of Penicillium purpurogenum, which led to the configuration revisions of purpurogenolide C (1a), berkeleyacetal B (2a), chrysogenolide F (3a), and berkeleyacetal C (4a) as compounds 1-4, respectively. Furthermore, extensive re-evaluation of the experimental and computational 13C NMR chemical shifts of the reported 39 SIMs and NSIMs provided an empirical approach for determining the C-9 relative configuration, according to the 13C NMR chemical shifts of C-9, which contributed to the configuration revisions of another three SIMs (5a and 6a) and NSIMs (7a), denoted as compounds 5-7, respectively. Biological assays indicated that compound 3 exhibited cytotoxic activity against HepG2 and A549 cell lines with IC50 values of 5.58 and 6.80 µM, respectively. Compounds 2-4, 8, 9, and 32 showed moderate hepatoprotective activity at 10 µM in the APAP-induced HepG2 cell injury model.

Citri Reticulatae Pericarpium alleviates postmyocardial infarction heart failure by upregulating PPARγ expression.

Heart failure after myocardial infarction (MI) is the leading cause of death worldwide. Citri Reticulatae Pericarpium (CRP) is a traditional Chinese herbal medicine that has been used in the clinic for centuries. In this study, we aimed to investigate the roles of CRP in cardiac remodelling and heart failure after MI, as well as the molecular mechanisms involved. Male C57BL/6 mice aged 8 weeks were subjected to coronary artery ligation to mimic the clinical situation in vivo. Echocardiography was used to assess the systolic function of the mouse heart. Masson trichrome staining and Wheat germ agglutinin (WGA) staining were utilised to determine the fibrotic area and cross-sectional area of the mouse heart, respectively. Cardiomyocytes and fibroblasts were isolated from neonatal rats aged 0-3 days in vitro using enzyme digestion. TUNEL staining and EdU staining were performed to evaluate apoptosis and proliferation, respectively. Gene expression changes were analysed by qRT-PCR, and protein expression changes were assessed by Western blotting. Our findings revealed that CRP attenuated cardiac hypertrophy, fibrosis and apoptosis and alleviated heart failure after MI in vivo. Furthermore, CRP mitigated cardiomyocyte apoptosis and fibroblast proliferation and differentiation into myofibroblasts. In addition, the PPARγ inhibitor T0070907 completely abolished the abovementioned beneficial effects of CRP, and the PPARγ activator rosiglitazone failed to further ameliorate cardiac apoptosis and fibrosis in vitro. CRP alleviates cardiac hypertrophy, fibrosis, and apoptosis and can ameliorate heart failure after MI via activation of PPARγ.

[Screening methods of traditional Chinese medicine for coronary heart disease and angina pectoris: an exploration based on core outcome set and fuzzy comprehensive evaluation].

It was pointed out in Opinions on Promoting the Inheritance, Innovation and Development of Traditional Chinese Medicine issued by the State Council in 2019 that 100 varieties of traditional Chinese medicine(TCM) with unique curative effects should be screened out within about three years. Due to the multi-component and multi-target mechanisms of TCM varieties, it is difficult to directly and simply evaluate their multi-dimensional clinical value using methods applicable to chemical or biological agents. The heterogeneity of outcomes for similar TCM makes it difficult to determine the advantages of similar products. The fuzzy comprehensive evaluation method that is developed on the basis of core outcome set and fuzzy mathematics for clinical efficacy evaluation of TCM may solve these problems. This study developed a fuzzy comprehensive evaluation model for the clinical efficacy evaluation of Chinese patent me-dicines for coronary heart disease and angina pectoris, and selected the previous normative studies with complete or incomplete data for verifying the model application. The results showed that original studies with complete data failed to evaluate and compare the comprehensive efficacy of different interventions. The original research only mentioned the advantages and disadvantages of different interventions in different aspects. The comprehensive clinical efficacy of three different interventions obtained through fuzzy comprehensive evaluation was all graded as level Ⅱ. The original research with incomplete data drew the same conclusions as the fuzzy comprehensive evaluation, and the results of fuzzy comprehensive evaluation can provide more comprehensive information. Therefore, the fuzzy comprehensive evaluation shows the products with overall advantages of clinical efficacy, which may become a feasible method for the screening of TCM.

[Progress of target determination and mechanism of bioactive components of traditional Chinese medicine].

The pharmacodynamic substances of traditional Chinese medicine(TCM) are the basis for the research of TCM and the development of innovative drugs. However, the lack of clarity of targets and molecular mechanisms is the bottleneck problem that restricts the research of pharmacodynamic substances of TCM. Bioactive components are the material basis of the efficacy of TCM, which exert activity by regulating the corresponding targets. Therefore, it is very important to identify the targets of the bioactive components to elucidate the pharmacological mechanism of TCM. Proteins are the most important drug targets, and study of the interaction between the proteins and bioactive components of TCM plays a key role in the development of pharmacological mechanism of TCM. In recent years, the main techniques for detecting the interaction between the bioactive components and proteins include surface plasmon resonance, fluorescence resonance energy transfer, bio-layer interference, molecular docking, proteome chip, target fishing, target mutant, and protein crystallization techniques, etc. This review summarized the biological target detection techniques and their applications in locating the targets of the bioactive components in TCM in the last decade, and this paper will provide useful strategies to elucidate the pharmacological mechanisms of TCM.

[Concept and method of evidence-based toxicology of traditional Chinese medicine from origin and development of evidence-based toxicology].

Advances in science and technology promote the rapid development of toxicological detection technologies. However, there is still a lack of decision-making tools for toxicological risk assessment, such as the lack of transparent schemes to evaluate current toxicological research and practice and the lag of toxicological testing tools to evaluate toxicity, resulting in difficulties in toxicity verification and hindering the transformation of toxicological research paradigm. Some scholars have proposed to integrate the concept of evidence-based medicine with the toxicological practice to improve the technical methods of toxicological research concept and risk assessment decision-making. With the promotion of relevant scholars and academic organizations, the concept and connotation of evidence-based toxicology have gradually become clear and a framework for research and practice has been initially formed. Although there are still many challenges, it also provides a new idea for the toxicity risk assessment and safe medication decision-making of traditional Chinese medicine(TCM). The era of digital intelligence has brought new opportunities and broad space for the development of TCM evidence-based toxicology. The exploration of TCM evidence-based toxicology from concept to method is an important embodiment of the development of TCM evidence-based toxicology, and will also promote the continuous enrichment and improvement of the research and practice system of TCM evidence-based toxicology.

[Establishment of multiple evidence-integrated evaluation and prediction method for "toxic" Chinese medicines].

Traditional Chinese medicine(TCM) carries the experience and theoretical knowledge of the ancients, and the use of "toxic" Chinese medicines is a major feature and advantage of TCM. "Toxic" Chinese medicines have unique clinical value and certain medication risk under the guidance of TCM theories such as compatibility for detoxification and treatment based on syndrome differentiation. In recent years, the safety events of Chinese medicines have occurred frequently, which has made the safety of Chinese medicine a public concern in China and abroad. However, limited by conventional cognitive laws and technical methods, basic research on toxicity of Chinese medicines fails to be combined with the clinical application. As a result, it is difficult to identify the clinical characteristics of, predict toxic and side effects of, or form a universal precise medication regimen for "toxic" Chinese medicines, which restricts the clinical application of them. In view of the problem that the toxicity of "toxic" Chinese medicines is difficult to be predicted and restricts the clinical application, the evidence-based research concept will provide new ideas for safe applcation of them in clinical practice. The integrated development of multiple disciplines and techniques in the field of big data and artificial intelligence will also promote the renewal and development of the research models for "toxic" Chinese medicines. Our team tried to propose the academic concept of evidence-based Chinese medicine toxicology and establish the data-intelligence research mode for "toxic" Chinese medicines and the intelligent risk prediction method for medicinal combination in the early stage, which provided methodological supports for solving the above problem. Thus, on the basis of summarizing the research status and problems of the clinical medication regimen of "toxic" Chinese medicines, our team took the evidence-based toxicology of TCM as the core concept, and tried to construct the multiple-evidence integrated evaluation and prediction method for "toxic" Chinese medicine, so as to guide the establishment of the non-toxic medication regimen of "toxic" Chinese medicines. Specifically, through the analysis of multivariate data obtained from the basic research, the evidence-based toxicology database of Chinese medicines and the individualized "toxicity-effect" intelligent prediction platform were built based on the disease-syndrome virtual patients, so as to identify the clinical characteristics and risks of "toxic" Chinese medicines and develop individualized medication regime. This study is expected to provide a methodological reference for the establishment of medication regimen and risk prevention strategy for "toxic" Chinese medicines. The method established in this study will bridge clinical research and basic research, enhance the transformation of the scientific connotation of attenuated compatibility, promote the development of evidence-based Chinese medicine toxicology, and ensure the clinical safety of "toxic" Chinese medicines.

[Trace therapeutic substances of traditional Chinese medicine: great resources of innovative drugs derived from traditional Chinese medicine].

The traditional Chinese medicine(TCM) contains very complex constituents. Besides the major constituents, there are a large number of unclear trace constituents with novel skeletons and potent bioactivities, which have been regarded as one of the important therapeutic substances and the great resources of innovative drugs derived from TCM. The present review highlighted that the development of the trace therapeutic substances of TCM is closely depends on the advanced technologies for their identification, isolation, structure elucidation, and bioactivity evaluation. Additionally, this paper reviewed the novel trace compounds derived from Chinese herbal medicines which have been published in Organic Letters during 2001-2021, and summarized the important licensed drugs originated from the trace therapeutic substances and the discovery and development of trace therapeutic substances of 8 kinds of Chinese herbal medicines. This review provides references for the research and development of TCM therapeutic substances and innovative drugs.

Efficacy of Sodium Tanshinone IIA Sulfonate in Patients with Non-ST Elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: Results from a Multicentre, Controlled, Randomized Trial.

BACKGROUND: Sodium tanshinone IIA sulfonate (STS) has been widely used by Chinese medicine practitioners for chronic cardiovascular diseases. However, its direct clinical efficacy in patients with acute coronary syndrome following percutaneous coronary intervention (PCI) has not been reported yet. The present trial aimed to investigate potential cardioprotection of STS in patients undergoing PCI for non-ST elevation acute coronary syndrome (NSTE-ACS). METHODS: In a randomized, double-blind, placebo-controlled trial, 372 patients with NSTE-ACS were randomly assigned to receive STS (n = 192) or saline (n = 180) for 2 days before and 3 days after PCI along with standard therapy. The primary endpoint was the composite incidence of major adverse cardiac events (MACEs), including death, non-fatal myocardial infarction, repeated revascularization of the target vessel, and stent thrombosis, within 30 days after PCI. RESULTS: The 30-day MACEs occurred in 18.8% of the patients in the STS group and in 27.2% of the patients in the control group (P = 0.038); this difference was mostly driven by reduction of myocardial infarction incidence (17.2% vs. 26.7%, P = 0.027). Post-procedural elevation of troponin-I was also significantly lower in the STS group (26.56% vs. 47.78%, P < 0.001). Multivariable analysis identified STS as a predictor of decreased risk of MACE occurrence (odds ratio: 0.60, 95% confidence interval: 0.36 to 0.99; P = 0.045). CONCLUSION: Addition of STS to the standard treatments recommended by the current practice guidelines in patients with NSTE-ACS undergoing PCI could reduce myocardial injury and the occurrence of short-term cardiovascular events, primarily driven by non-fatal myocardial infarction. TRIAL REGISTRATION: ChiCTR-TRC-14005182.

Association between birth weight and risk of cardiovascular disease: Evidence from UK Biobank.

BACKGROUND AND AIMS: Birth weight has been linked to cardiovascular disease (CVD) risk in adulthood, but no consensus has emerged on the threshold of birth weight for the lowest CVD risk and few studies have examined potential interaction between birth weight and adult adiposity. METHODS AND RESULTS: A total of 256,787 participants, who had birth weight data and were free of CVD at baseline, were included from UK Biobank. Multivariate restricted cubic splines and Cox regression models were used to assess the association between birth weight and CVD. We observed nonlinear inverse associations of birth weight with the risk of coronary heart disease (CHD), stroke, and heart failure. Participants with the first quintile of birth weight (≤2.85 kg) had higher risks for CHD (hazard ratio [HR] = 1.23, 95% confidence interval [CI]: 1.15-1.32), stroke (HR = 1.19, 95% CI: 1.03-1.37), and heart failure (HR = 1.28, 95% CI: 1.11-1.48), as compared to the fourth quintile (3.41-3.79 kg). There was a significant interaction between birth weight and adult body mass index (BMI) on CHD and heart failure (both P for interaction <0.001), showing the highest risk for those who had birth weight ≤2.85 kg and BMI ≥30 kg/m2 (HR = 1.96, 95% CI: 1.70-2.25 and HR = 2.39, 95% CI: 1.77-3.22, respectively). CONCLUSIONS: Our findings indicate nonlinear inverse associations between birth weight and CVD risk, with a threshold of 3.41-3.79 kg for the lowest risk. Moreover, low birth weight may interact with adult obesity to increase the risk of CHD and heart failure.

Hepatic small extracellular vesicles promote microvascular endothelial hyperpermeability during NAFLD via novel-miRNA-7.

BACKGROUND: A recent study has reported that patients with nonalcoholic fatty liver disease (NAFLD) are more susceptible to coronary microvascular dysfunction (CMD), which may predict major adverse cardiac events. However, little is known regarding the causes of CMD during NAFLD. In this study, we aimed to explore the role of hepatic small extracellular vesicles (sEVs) in regulating the endothelial dysfunction of coronary microvessels during NAFLD. RESULTS: We established two murine NAFLD models by feeding mice a methionine-choline-deficient (MCD) diet for 4 weeks or a high-fat diet (HFD) for 16 weeks. We found that the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome-dependent endothelial hyperpermeability occurred in coronary microvessels during both MCD diet and HFD-induced NAFLD. The in vivo and in vitro experiments proved that novel-microRNA(miR)-7-abundant hepatic sEVs were responsible for NLRP3 inflammasome-dependent endothelial barrier dysfunction. Mechanistically, novel-miR-7 directly targeted lysosomal associated membrane protein 1 (LAMP1) and promotes lysosomal membrane permeability (LMP), which in turn induced Cathepsin B-dependent NLRP3 inflammasome activation and microvascular endothelial hyperpermeability. Conversely, a specific novel-miR-7 inhibitor markedly improved endothelial barrier integrity. Finally, we proved that steatotic hepatocyte was a significant source of novel-miR-7-contained hepatic sEVs, and steatotic hepatocyte-derived sEVs were able to promote NLRP3 inflammasome-dependent microvascular endothelial hyperpermeability through novel-miR-7. CONCLUSIONS: Hepatic sEVs contribute to endothelial hyperpermeability in coronary microvessels by delivering novel-miR-7 and targeting the LAMP1/Cathepsin B/NLRP3 inflammasome axis during NAFLD. Our study brings new insights into the liver-to-microvessel cross-talk and may provide a new diagnostic biomarker and treatment target for microvascular complications of NAFLD.

[Meta-analysis of effect of Qishen Yiqi Dripping Pills combined with Western medicine on adverse cardiovascular events and quality of life after percutaneous coronary intervention].

To systemically evaluate the effect of Qishen Yiqi Dripping Pills combined with Western medicine on adverse cardiovascular events and quality of life after percutaneous coronary intervention(PCI). A total of 7 Chinese and English databases including CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library and Web of Science were searched by computer to collect the randomized controlled trials(RCTs) on Qishen Yiqi Dripping Pills combined with Western medicine in the treatment of patients with coronary heart disease after PCI with the retrieval time from the database establishment to April 1, 2020. Two researchers independently conducted li-terature screening, data extraction and bias risk assessment. Then, Meta-analysis was performed by using RevMan 5.3 software. A total of 31 RCTs were included, involving 3 537 patients. The results of Meta-analysis showed that in terms of major adverse cardiovascular events(MACE) after PCI, the combination of Qishen Yiqi Dripping Pills could significantly reduce the recurrence of angina pectoris, incidence of arrhythmia, heart failure and re-revascularization, and the effect was better than that of Western medicine treatment alone. However, there was no significant difference between the two groups in the improvement of non-fatal myocardial infarction, cardiac death, stent restenosis, stroke and other adverse cardiovascular events. In terms of improving left ventricular ejection fraction(LVEF), 6 min walking test(6 MWT), high-sensitivity C-reactive protein(hs-CRP) and Seattle angina pectoris scale(SAQ), the combination of Qishen Yiqi Dripping Pills and Western medicine treatment had obvious advantages over Western medicine treatment alone in increasing LVEF, 6 MWT and SAQ, and reducing the level of hs-CRP, with statistically significant differences. There were few adverse reactions in both groups, and there was no significant difference between the two groups. The main manifestations were gastrointestinal reactions, rash, gingiva and other small bleeding, and no serious adverse reactions occurred. The above reactions could disappear after drug withdrawal or symptomatic treatment. The application of Qishen Yiqi Dripping Pills combined with Western medicine in the treatment of patients after PCI could reduce the occurrence of MACE, improve the clinical efficacy, quality of life and prognosis in a safe and reliable manner. However, due to the quantity and quality limitations of included studies, more standardized, rigo-rous and high-quality clinical studies are still needed to further verify the above conclusions.