Efficacy and safety of Panax notoginseng saponin injection in the treatment of acute myocardial infarction: a systematic review and meta-analysis of randomized controlled trials.

Purpose: This study aimed to assess the efficacy and safety of Panax notoginseng saponin (PNS) injection, when combined with conventional treatment (CT), for acute myocardial infarction (AMI). Methods: Comprehensive searches were conducted in seven databases from inception until 28 September 2023. The search aimed to identify relevant randomized controlled trials (RCTs) focusing on PNS injection in the context of AMI. This meta-analysis adhered to the PRISMA 2020 guidelines, and its protocol was registered with PROSPERO (number: CRD42023480131). Result: Twenty RCTs involving 1,881 patients were included. The meta-analysis revealed that PNS injection, used adjunctively with CT, significantly improved treatment outcomes compared to CT alone, as evidenced by the following points: (1) enhanced total effective rate [OR = 3.09, p < 0.05]; (2) decreased incidence of major adverse cardiac events [OR = 0.32, p < 0.05]; (3) reduction in myocardial infarct size [MD = -6.53, p < 0.05]; (4) lower ST segment elevation amplitude [MD = -0.48, p < 0.05]; (5) mitigated myocardial injury as indicated by decreased levels of creatine kinase isoenzymes [MD = -11.19, p < 0.05], cardiac troponin T [MD = -3.01, p < 0.05], and cardiac troponin I [MD = -10.72, p < 0.05]; (6) enhanced cardiac function, reflected in improved brain natriuretic peptide [MD = -91.57, p < 0.05], left ventricular ejection fraction [MD = 5.91, p < 0.05], left ventricular end-diastolic dimension [MD = -3.08, p < 0.05], and cardiac output [MD = 0.53, p < 0.05]; (7) reduced inflammatory response, as shown by lower levels of C-reactive protein [MD = -2.99, p < 0.05], tumor necrosis factor-α [MD = -6.47, p < 0.05], interleukin-6 [MD = -24.46, p < 0.05], and pentraxin-3 [MD = -2.26, p < 0.05]; (8) improved vascular endothelial function, demonstrated by decreased endothelin-1 [MD = -20.56, p < 0.05] and increased nitric oxide [MD = 1.33, p < 0.05]; (9) alleviated oxidative stress, evidenced by increased superoxide dismutase levels [MD = 25.84, p < 0.05]; (10) no significant difference in adverse events [OR = 1.00, p = 1.00]. Conclusion: This study highlighted the efficacy and safety of adjunctive PNS injections in enhancing AMI patient outcomes beyond CT alone. Future RCTs need to solidify these findings through rigorous methods. Systematic Review Registration: (https://www.crd.york.ac.uk/PROSPERO/), identifier (CRD42023480131).

Trends in gut-heart axis and heart failure research (1993-2023): A bibliometric and visual analysis.

Background: The incidence of heart failure, the terminal stage of several cardiovascular diseases, is increasing owing to population growth and aging. Bidirectional crosstalk between the gut and heart plays a significant role in heart failure. This study aimed to analyze the gut-heart axis and heart failure from a bibliometric perspective. Methods: We extracted literature regarding the gut-heart axis and heart failure from the Web of Science Core Collection database (January 1, 1993, to June 30, 2023) and conducted bibliometric and visualization analyses using Microsoft Excel, CiteSpace, VOSviewer, and the R package "bibliometrix." Results: The final analysis included 1646 articles with an average of 35.38 citations per article. Despite some fluctuations, the number of articles published per year has steadily increased over the past 31 years, particularly since 2018. A total of 9412 authors from 2287 institutions in 86 countries have contributed to this field. The USA and China have been the most productive countries, with the Cleveland Clinic in the USA and Charité-Universitätsmedizin Berlin in Germany being the most active institutions. The cooperation between countries/regions and institutions was relatively close. Professor Tang WHW was the most productive author in the field and the journal Shocks published the highest number of articles. "Heart failure," "gut microbiota," "trimethylamine N-oxide," and "inflammation" were the most common keywords, representing the current research hotspots. The keyword burst analysis indicated that "gut microbiota" and "short-chain fatty acids" are the current frontier research topics in this field. Conclusion: Research on the gut-heart axis and heart failure is increasing. This bibliometric analysis indicated that the mechanisms associated with the gut-heart axis and heart failure, particularly the gut microbiota, trimethylamine N-oxide, inflammation, and short-chain fatty acids, will become hotspots and emerging trends in research in this field. These findings provide valuable insights into current research and future directions.

Hypertension in non-obese children and BMI in adulthood: the Bogalusa heart study.

OBJECTIVE: This study explored the association between hypertension(HTN) in non-obese children body mass index (BMI) in adulthood. METHODS: A retrospective analysis of 1111 participants from the Bogalusa Heart Study was conducted, in which data on hypertension history during childhood in non-obese children, anthropometric and cardiovascular risk factors and other indicators from cross-sectional examinations in adulthood were collected. BMI was used as both a continuous and a categorical variable, and multivariate linear regression modelling and logistic regression modelling were used. RESULTS: Of the 1111 participants finally enrolled, 40 (3.60%) had HTN during childhood. After adjusting for demographic characteristics, lipid, glucose and insulin levels in childhood, and smoking status, alcohol intake, and disease history as adults, HTN among non-obese children was positively associated with BMI in adulthood (ß = 2.64 kg/m2, 95% CI: 0.88-4.40, P = 0.0033), and the odds of being overweight or obese was 3.71 times higher in the group with a history of hypertension in childhood than those without a history of HTN(95% CI: 1.11-12.46, P = 0.0337). CONCLUSION: Among non-obese children, hypertension is at risk for higher levels of BMI in adulthood. Identifying and controlling blood pressure and childhood may aid in the prevention of adult obesity.

Remnant cholesterol associates with hypertension beyond low-density lipoprotein cholesterol among the general US adult population.

Background: Previous findings have indicated that elevated low-density lipoprotein cholesterol (LDL-C) and remnant cholesterol (RC) are associated with hypertension. We aim to explore whether higher RC levels may be associated with hypertension beyond LDL-C in the general US adult population. Methods: This study included 10,842 adults from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Weighted multivariable logistic regression models were used to estimate the odds ratios (ORs) of hypertension for LDL-C and RC. We also performed analyses examining the association between hypertension and LDL-C vs. RC concordant/discordant groups. Results: A total of 4,963 (41.54%, weighted) individuals had hypertension. The weighted median levels were LDL-C: 118mg/dL, RC: 20mg/dL. At lower LDL-C clinical cut-point, the proportion of discordantly high RC dramatically increased. After multivariable adjustment, log RC was associated with higher prevalence of hypertension [OR 2.54, 95% confidence interval (CI) 2.17-2.99]. Participants with the highest tertile of RC were more likely to have hypertension (OR 2.18; 95% CI 1.89-2.52) compared with those with the lowest tertile of RC. This association remained marked after including body mass index (BMI), LDL-C, high-density lipoprotein cholesterol (HDL-C) or triglycerides. The association between LDL-C and hypertension was absent after adjusting for BMI, RC or triglycerides. Compared with low LDL-C/low RC group, the discordant low LDL-C/high RC group was associated with hypertension (OR 2.04; 95% CI 1.72-2.42), whereas the high LDL-C/low RC group was not, regardless of BMI, HDL-C or triglycerides. Similar results were observed when examining discordance among different clinical cut-points, except for the cut-point of LDL-C 70 mg/dL and RC 13 mg/dL. To better understand the association, we performed an additional analysis, which showed that among participants with apolipoprotein B < median (92mg/dL), those with discordant RC ≥ median (20mg/dL) had significantly higher odds of having hypertension (OR 1.73; 95% CI 1.38-2.17). Conclusion: RC was associated with hypertension beyond LDL-C in the general US adult population. This association went beyond increased triglycerides levels, and lipoproteins other than apoB may be involved.

Berberine Decreases Thrombosis Potential Induced by a High-choline Diet by Inhibiting CutC Enzyme.

INTRODUCTION: Gut microbes influence thrombosis potential by generating trimethylamine N-oxide (TMAO). However, whether the antithrombotic effect of berberine is associated with TMAO generation remains unclear. OBJECTIVE: The present study was designed to explore whether berberine decreases the TMAO-induced thrombosis potential and the possible mechanism underneath it. METHODS: C57BL/6J female mice under a high-choline diet or standard diet were treated with/without berberine for 6 weeks. The TMAO level, carotid artery occlusion time following FeCl3 injury and platelet responsiveness were measured. The binding of berberine to the CutC enzyme was analysed with molecular docking, and molecular dynamics simulations were verified with enzyme activity assays. Results：The results showed that berberine increased the carotid artery occlusion time following FeCl3 injury and decreased the platelet hyperresponsiveness induced by a high-choline diet, both offset by intraperitoneal injection of TMAO. The effect of berberine on thrombosis potential was associated with decreasing the generation of TMAO by inhibiting the CutC enzyme. CONCLUSION: Targeting TMAO generation with berberine might be a promising therapy for ischaemic cardiac-cerebral vascular diseases.

[Application of "major scientific issues and engineering technology difficulties in traditional Chinese medicine(2019-2021)" in national science and t echnology layout].

In order to judge the future development trend of science and technology, plan ahead and lay out the frontier technology fields and directions, China Association of Chinese Medicine(CACM) has launched consultation projects for collecting "major scienti-fic issues and engineering technology difficulties in traditional Chinese medicine(TCM)" for the industry for three consecutive years since 2019. Up to now, 18 projects have been selected as major issues for research, and some experience and achievements have been made. These projects have been applied in important scientific and technological work such as scientific and technological planning and deployment at all levels of national, local, and scientific research institutions, the selection and cultivation of major national scientific and technological projects, and the construction of innovation bases, giving full play to the role of the think tank advisory committee of CACM. This study reviewed the selection of major issues for the first time, systematically combed its application in the national layout of science and technology, and put forward the existing problems and improvement suggestions, aiming to provide new ideas for further improving the selection of major issues and research direction, providing a theoretical basis and decision support for the national scientific and technological layout in the field of TCM, and promoting scientific and technological innovation to facilitate the high quality development of TCM.

The effectiveness and safety of Chinese Patent Medicines based on syndrome differentiation in patients following percutaneous coronary intervention due to acute coronary syndrome (CPM trial): A nationwide Cohort Study.

BACKGROUND: The incidence of cardiovascular events remains not unusual in patients following percutaneous coronary intervention (PCI) due to acute coronary syndrome (ACS). Chinese patent medicine (CPM) therapy based on syndrome differentiation in addition to conventional medicine (CM) had been expected to further reduce the risk of cardiovascular events. PURPOSE: To assess the effectiveness and safety of CPM based on syndrome differentiation in patients following PCI due to ACS. STUDY DESIGN: Nationwide prospective cohort study. METHODS: CPM study was conducted in 40 centers in mainland China. Patients following PCI due to ACS entered to syndrome differentiation-based CPM (SDCPM) or CM group according to whether they received CPM or not. The CPM comprised Guanxin Danshen dripping pills, Qishen Yiqi dripping pills, or Danlou tablets, and was used correspondingly with the syndrome differentiation of traditional Chinese medicine. The follow-up time was 36 months. The primary endpoint was composed of cardiac death, non-fatal myocardial infarction and urgent revascularization. The secondary endpoint included rehospitalization due to ACS, heart failure, stroke, other thrombotic events. Seattle Angina Questionnaire (SAQ) was used to evaluate quality of life. RESULTS: Between February 2012 and December 2018, ascertainment of the primary endpoint was completed in 2,724 patients of follow-up. 1,380 patients were in SDCPM group. At a median follow-up of 541 (interquartile range 513 - 564) days, the primary endpoint occurred in 126 (8.61%) patients in SDCPM group and 167 (11.62%) patients in CM group (adjusted hazard ratio [HR] = 0.70; [95% confidence interval [CI] 0.55 - 0.89]; p = 0.003). The secondary endpoint occurred in 144 (9.84%) patients in SDCPM group and 197 (13.71%) patients in CM group (adjusted HR = 0.66; [95% CI 0.53 - 0.82]; p < 0.001). The SAQ score in SDCPM group was higher than CM group (366.78 ± 70.19 vs 356.43 ± 73.80, p < 0.001). There were no significant differences of adverse events between two groups. CONCLUSION: In patients following PCI due to ACS, SDCPM in addition to CM treatment reduced the primary and secondary endpoints, as well as improved the quality of life without adverse events.

DRONet: effectiveness-driven drug repositioning framework using network embedding and ranking learning.

As one of the most vital methods in drug development, drug repositioning emphasizes further analysis and research of approved drugs based on the existing large amount of clinical and experimental data to identify new indications of drugs. However, the existing drug repositioning methods didn't achieve enough prediction performance, and these methods do not consider the effectiveness information of drugs, which make it difficult to obtain reliable and valuable results. In this study, we proposed a drug repositioning framework termed DRONet, which make full use of effectiveness comparative relationships (ECR) among drugs as prior information by combining network embedding and ranking learning. We utilized network embedding methods to learn the deep features of drugs from a heterogeneous drug-disease network, and constructed a high-quality drug-indication data set including effectiveness-based drug contrast relationships. The embedding features and ECR of drugs are combined effectively through a designed ranking learning model to prioritize candidate drugs. Comprehensive experiments show that DRONet has higher prediction accuracy (improving 87.4% on Hit@1 and 37.9% on mean reciprocal rank) than state of the art. The case analysis also demonstrates high reliability of predicted results, which has potential to guide clinical drug development.

The mechanisms of Qizhu Tangshen formula in the treatment of diabetic kidney disease: Network pharmacology, machine learning, molecular docking and experimental assessment.

BACKGROUND: Qizhu Tangshen Formula (QZTS) has been shown therapeutic effects on diabetic kidney disease (DKD). However, to date, the pharmacological mechanisms remain vague. METHODS: To explore the underlying mechanisms of QZTS in treating DKD using network pharmacology, machine learning, molecular docking and experimental assessment. RESULTS: First, we found that QZTS improved glycolipid metabolism disorder, decreased proteinuria and alleviated kidney tissue injury in DKD model KKAy mice. Then, by integrating multiple databases, a total of 96 targets of 74 active compounds in QZTS and 759 DKD-related genes were acquired. Next, we identified 13 hub targets of QZTS in DKD by three rank algorithms, including functional similarity, topological similarity and shortest path. Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses demonstrated that the pathways mainly centered on the processes of glycolipid metabolism disorder, inflammation and angiogenesis. Among them, VEGF signaling pathway was significantly enriched. Molecular docking showed that key active compounds of QZTS all had relatively good binding affinity with predicted hub targets. Finally, animal experiments found that QZTS significantly inhibited the secretion of plasma VEGF and downregulated the protein and mRNA expression levels of AKT, p38MAPK and VEGFR2. CONCLUSION: Our results indicated that QZTS treated DKD via multiple targets and pathways and the VEGF signaling pathway may be highly involved in this process.

Beneficial effects of folic acid on inflammatory markers in the patients with metabolic syndrome: Meta-analysis and meta-regression of data from 511 participants in 10 randomized controlled trials.

Previous clinical studies on the anti-inflammatory effects of folic acid (FA) in patients with metabolic syndrome (MetS) have shown controversial results. This study aimed to synthesize the evidence on the effect of FA on inflammatory marker levels in MetS patients. We screened PubMed, Embase, Medline, and the Cochrane Library (from inception to March 2022) to identify relevant randomized controlled trials (RCTs). DerSimonian and Laird random effects were used to estimate the pooled weighted mean difference (WMD) with 95% confidence interval (CI). Funnel plot, Egger's test, and the Begg-Mazumdar correlation test was used to assess publication bias. Subgroup analysis, meta-regression and sensitivity analysis were performed to find out possible sources of between-study heterogeneity. Ten RCTs with a total of 511 participants were included. The analysis showed that FA reduced high sensitivity C-reactive protein (hs-CRP) (WMD, -0.94; 95% CI, -1.56 to -0.32; P = 0.00), interleukin-6 (IL-6) (WMD, -0.39; 95% CI, -0.51 to -0.28; P = 0.00), and tumor necrosis factor-alpha (TNF-α) (WMD, -1.28; 95% CI, -1.88 to -0.68; P = 0.00), but did not decrease the C-reactive protein (CRP) (WMD, 0.10; 95% CI, -0.13 to 0.33; P = 0.38). Sensitivity analysis, subgroup analysis, and meta-regression showed that the effect sizes remained stable. Our findings suggest that FA supplementation could reduce inflammatory markers, such as hs-CRP, IL-6, TNF-α in patients with MetS. This study is registered with PROSPERO (CRD42021223843).

Potential Benefits of Selenium Supplementation in Reducing Insulin Resistance in Patients with Cardiometabolic Diseases: A Systematic Review and Meta-Analysis.

BACKGROUND: Selenium is a trace element that has been reported to be effective in regulating glucose and lipid metabolism. However, there is conflicting evidence from different clinical trials of selenium supplementation in treating cardiometabolic diseases (CMDs). OBJECTIVE: This meta-analysis aimed to identify the effects of selenium supplementation on insulin resistance, glucose homeostasis, and lipid profiles in patients with CMDs. METHODS: Randomized controlled trials (RCTs) of selenium supplementation for treating CMDs were screened in five electronic databases. Insulin levels, homeostatic model assessment of insulin resistance (HOMA-IR), fasting plasma glucose (FPG), and glycosylated hemoglobin A1C (HbA1c) were defined as the primary outcome markers, and lipid profiles were considered the secondary outcome markers. RESULTS: Ten studies involving 526 participants were included in the meta-analysis. The results suggested that selenium supplementation significantly reduced serum insulin levels (standardized men difference [SMD]: -0.53; 95% confidence interval [CI] [-0.84, -0.21], p = 0.001, I2 = 68%) and HOMA-IR (SMD: -0.50, 95% CI [-0.86, -0.14], p = 0.006, I2 = 75%) and increased high-density lipoprotein cholesterol (HDL-C) levels (SMD: 0.97; 95% CI [0.26, 1.68], p = 0.007, I2 = 92%), but had no significant effect on FPG, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and very low-density lipoprotein cholesterol (VLDL-C). CONCLUSION: Current evidence supports the beneficial effects of selenium supplementation on reducing insulin levels, HOMA-IR, and increasing HDL-C levels. Selenium supplementation may be an effective strategy for reducing insulin resistance in patients with CMDs. However, more high-quality clinical studies are needed to improve the certainty of our estimates.

Qing-Xin-Jie-Yu Granule alleviates atherosclerosis by reshaping gut microbiota and metabolic homeostasis of ApoE-/- mice.

BACKGROUND: Atherosclerosis (AS) is a key pathological factor in cardiovascular disease (CVD) and is characterized by high mortality and morbidity worldwide. Metabolic disorders, including pathoglycemia and dyslipidemia that lead to chronic inflammation, represent the prominent pathological characteristics of atherosclerotic CVD, Qing-Xin-Jie-Yu Granule (QXJYG) is a Chinese traditional decoction that has been clinically proven to be effective for patients with CVD. However, the underlying mechanisms have not been completely elucidated. PURPOSE: To investigate the protective effects of QXJYG against AS and its potential mechanisms. METHODS: QXJYG was orally administered at doses of 1.664 and 4.992 g·kg-1·d-1 in a high-fat diet (HFD)-induced AS model using ApoE-/- mice. Histopathological and immunohistochemical analyses, ELISA, untargeted and targeted metabolomics analysis, 16S rRNA analysis, and RT-qPCR were performed to identify the therapeutic effects and mechanisms of QXJYG in treating HFD-induced AS. RESULTS: QXJYG retarded HFD-induced weight gain and reduced the increased serum levels of total cholesterol, triglycerides, and low-density lipoprotein-cholesterol, whereas high-dose QXJYG increased the serum level of high-density lipoprotein-cholesterol in HFD-fed ApoE-/- mice. Meanwhile, QXJYG reduced the serum levels, as well as aortas mRNA levels of the inflammatory cytokines, IL-1ß and IL-6, which indicates that QXJYG is effective against metaflammation. Mechanistically, QXJYG reshaped the gut microbiota and its associated bile acids (BAs) metabolomic phenotype, partly by increasing the levels of BA synthesis enzymes, hepatic CYP7A1, and CYP27A1, while decreasing ileal FGF15 and ß-Klotho mRNA expression, favoring facilitated de novo BAs synthesis and thereby driving cholesterol catabolic excretion. CONCLUSION: Our findings indicate that QXJYG is effective against HFD-triggered chronic inflammation, and contributes to the alleviation of AS development, and the antiatherogenic properties of QXJYG may be partly due to the remodeling of the gut microbiota and BA metabolism. Although the results are encouraging, further clinical studies of anti-AS herbal medicines are required to elucidate the full potential of the gut microbiota and BA metabolism.

Lipid-Lowering Efficacy of Kuding Tea in Patients With Metabolic Disorders: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Kuding tea (KT), traditional tea material and widely used in China, has been found to have lipid-lowering effect in clinical and experimental studies. However, there has been no systematic review of the evidence on this subject. Methods: Eight electronic databases were searched from database inception until September 2021 for relevant randomized controlled trials (RCTs). We used the Cochrane Reviewer's Handbook to assess the quality of the included studies. Weighted mean difference (WMD) and 95% confidence interval (CI) were used to measure the pooled effect size by random-effects model. Funnel plot, Egger regression test, and the Begg's test was used to assess publication bias. Results: Eight RCTs involving 716 patients were included in our meta-analysis. Comparing with the control group, KT group reduced serum total cholesterol (TC) levels (WMD: -0.56 mmol/L; 95% CI: -0.64, -0.47; I2 = 56.56%; P = 0.00), triglyceride (TG) levels (WMD: -0.30 mmol/L; 95% CI: -0.35, -0.24; I 2 = 88.60%; P = 0.00), and low-density lipoprotein cholesterol (LDL-C) levels (WMD: -0.29 mmol/L; 95% CI: -0.37, -0.21; I2 = 89.43%; P = 0.00), but no significant effects on high-density lipoprotein cholesterol (HDL-C) (WMD: 0.07 mmol/L; 95% CI: -0.02, 0.16; I 2 = 93.92%; P = 0.12). The results of sensitivity analysis were not altered after removing each study in turn. Subgroup analyses showed that KT intervention period was the source of heterogeneity. Following analysis, results revealed that long-term (>4 weeks and ≤8 weeks) use of KT increased HDL-C levels (WMD: 0.19; 95% CI: 0.13, 0.25). In addition, both the sensitivity analysis and subgroup analysis showed that our results were robust. No potentially significant publication bias was found from the funnel plot, Begg-Mazumdar correlation test and Egger regression test. Conclusion: KT supplementation can effectively improve lipid profile and KT is a promising approach to reduce blood lipid level in patients with metabolic disorders. Systematic Review Registration: [www.crd.york.ac.uk/prospero], identifier [CRD42020221850].

Lipid-Lowering Efficacy of the Capsaicin in Patients With Metabolic Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Patients with metabolic syndrome (MetS) have increased cardiovascular risk. Capsaicin (CAP) has been shown to reduce lipids, but efficacy for patients with MetS is unknown. Methods: A systematic review was performed according to PRISMA guidelines, to compare the effects of CAP against a placebo. Differences in the weight mean difference (WMD) with 95% confidence intervals (95% CI) were then pooled using a random effects model. Results: Nine randomized controlled trials including 461 patients were identified in the overall analysis. CAP significantly decreased total cholesterol (TC) (WMD = -0.48, 95% CI: -0.63 to -0.34, I 2= 0.00%) and low-density lipoprotein cholesterol (LDL-C) (WMD = -0.23, 95% CI: -0.45 to -0.02, I 2 = 68.27%) among patients with MetS. No significant effects of CAP were found on triglycerides (TG) or high-density lipoprotein cholesterol (HDL-C) (WMD = -0.40, 95% CI: -1.50 to 0.71, I 2 = 98.32%; WMD = -0.08, 95% CI: -0.21 to 0.04, I 2 = 86.06%). Subgroup analyses indicated that sex and intervention period were sources of heterogeneity. The results revealed that CAP decreased TG levels in women (WMD = -0.59, 95% CI: -1.07 to -0.10) and intervention period <12 weeks (WMD = -0.65; 95% CI: -1.10 to -0.20). And there was no potential publication bias according to funnel plot, Begg' test and Egger regression test. Conclusions: CAP supplementation is a promising approach to decreasing TC and LCL-C levels in patients with MetS. However, short-term (<12 weeks) use of CAP in women may also reduce TG levels. Systematic Review Registration: Identifier: CRD42021228032.

PDGNet: Predicting Disease Genes Using a Deep Neural Network With Multi-View Features.

The knowledge of phenotype-genotype associations is crucial for the understanding of disease mechanisms. Numerous studies have focused on developing efficient and accurate computing approaches to predict disease genes. However, owing to the sparseness and complexity of medical data, developing an efficient deep neural network model to identify disease genes remains a huge challenge. Therefore, we develop a novel deep neural network model that fuses the multi-view features of phenotypes and genotypes to identify disease genes (termed PDGNet). Our model integrated the multi-view features of diseases and genes and leveraged the feedback information of training samples to optimize the parameters of deep neural network and obtain the deep vector features of diseases and genes. The evaluation experiments on a large data set indicated that PDGNet obtained higher performance than the state-of-the-art method (precision and recall improved by 9.55 and 9.63 percent). The analysis results for the candidate genes indicated that the predicted genes have strong functional homogeneity and dense interactions with known genes. We validated the top predicted genes of Parkinson's disease based on external curated data and published medical literatures, which indicated that the candidate genes have a huge potential to guide the selection of causal genes in the 'wet experiment'. The source codes and the data of PDGNet are available at https://github.com/yangkuoone/PDGNet.

A Bibliometric Analysis of Pyroptosis From 2001 to 2021.

Background: Pyroptosis is a new programmed cell death discovered in recent years. Pyroptosis plays an important role in various diseases. Nevertheless, there are few bibliometric analysis systematically studies this field. We aimed to visualize the research hotspots and trends of pyroptosis using a bibliometric analysis to help understand the future development of basic and clinical research. Methods: The articles and reviews regarding pyroptosis were culled from Web of Science Core Collection. Countries, institutions, authors, references and keywords in this field were visually analyzed by using CtieSpace and VOSviewer software. Results: A total of 2845 articles and reviews were included. The number of articles regarding pyroptosis significantly increased yearly. These publications mainly come from 70 countries led by China and the USA and 418 institutions. We identified 605 authors, among which Thirumaladevi Kanneganti had the most significant number of articles, and Shi JJ was co-cited most often. Frontiers in immunology was the journal with the most studies, and Nature was the most commonly cited journal. After analysis, the most common keywords are nod like receptor family pyrin domain containing 3 inflammasome, apoptosis, cell death, gasdermin D, mechanism, caspase-1, and others are current and developing areas of study. Conclusion: Research on the pyroptosis is flourishing. Cooperation and exchanges between countries and institutions must be strengthened in the future. The related pathway mechanism of pyroptosis, the relationship between pyroptosis and other types of programmed cell deaths as well as the role of pyroptosis in various diseases have been the focus of current research and developmental trends in the future research.

A Bibliometric Analysis of Exosomes in Cardiovascular Diseases From 2001 to 2021.

Background: Exosomes in cardiovascular diseases (CVDs) have become an active research field with substantial value and potential. Nevertheless, there are few bibliometric studies in this field. We aimed to visualize the research hotspots and trends of exosomes in CVDs using a bibliometric analysis to help understand the future development of basic and clinical research. Methods: The articles and reviews regarding exosomes in the CVDs were culled from the Web of Science Core Collection, and knowledge maps were generated using CiteSpace and VOSviewer software. Results: A total of 1,039 articles were included. The number of exosome articles in the CVDs increased yearly. These publications came from 60 countries/regions, led by the US and China. The primary research institutions were Shanghai Jiao Tong University and Nanjing Medical University. Circulation Research was the journal and co-cited journal with the most studies. We identified 473 authors among which Lucio Barile had the most significant number of articles and Thery C was co-cited most often. After analysis, the most common keywords are myocardium infarction, microRNA and mesenchymal stem cells. Ischemic heart disease, pathogenesis, regeneration, stem cells, targeted therapy, biomarkers, cardiac protection, and others are current and developing areas of study. Conclusion: We identified the research hotspots and trends of exosomes in CVDs using bibliometric and visual methods. Research on exosomes is flourishing in the cardiovascular medicine. Regenerative medicine, exosome engineering, delivery vehicles, and biomarkers will likely become the focus of future research.

Efficacy and Safety of Xinyue Capsule for Coronary Artery Disease after Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

To evaluate the efficacy and safety of Xinyue capsule (XYC) in the treatment of coronary artery disease (CAD) after percutaneous coronary intervention (PCI), databases including MEDLINE, EMBASE (Ovid), PubMed, Google Scholar, Cochrane Central Register of Controlled Trials (CENTRAL), China National Knowledge Infrastructure database (CNKI), Wanfang, and VIP were searched to identify randomized controlled trials (RCTs) on XYC in CAD after PCI published before October 2020. Data extraction, methodological quality assessment, and data analysis were performed according to the Cochrane standard. Dichotomous data were shown as risk ratios (RRs) with a 95% confidence interval (CI). All analyses were done with Review Manager, version 5.3. The quality of evidence was assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. A total of 9 related studies from 166 related articles were identified, which included 2979 patients. Compared with conventional treatment alone (or placebo plus), XYC decreased cardiovascular events [RR = 0.37, 95% CI (0.27, 0.51), I 2 = 0%] (nonfatal myocardial infarction [RR = 0.26, 95% CI (0.10, 0.70), I 2 = 0%], revascularization [RR = 0.38, 95% CI (0.24, 0.61), I 2 = 0%], and rehospitalization due to ACS [RR = 0.48, 95% CI (0.33, 0.68), I 2 = 0%]) and improved cardiac function (LVEF [RR = 6.93, 95% CI (4.99, 8.87), I 2 = 81%], LVEDV [RR = -4.07, 95% CI (-5.61, -2.54), I 2 = 7%], and LVESV [RR = -4.32, 95% CI (-5.90, -2.74), I 2 = 50%]) in patients after PCI. In addition, XYC reduced serum NT-pro-BNP [RR = -126.91, 95% CI (-231.51, -22.31), I 2 = 69%]. However, XYC had little effect on cardiovascular death [RR = 0.47, 95% CI (0.13, 1.68), I 2 = 0%], stroke [RR = 0.52, 95% CI (0.23, 1.20), I 2 = 0%], heart failure [RR = 0.53, 95% CI (0.24, 1.20), I 2 = 0%], and quality of life [RR = -1.37, 95% CI (-4.97, 2.22), I 2 = 93%]. Thus, this meta-analysis suggests that XYC has potential advantages in reducing the occurrence of cardiovascular events after PCI, improving cardiac function, and reducing serum NT-pro-BNP. This potential benefit requires a high-quality RCT to assess.

The Effect of Prebiotic Products on Decreasing Adiposity Parameters in Overweight and Obese Individuals: A Systematic Review and Meta- Analysis.

BACKGROUND: Prebiotics are substrates selectively utilized by host microorganisms to confer health benefits. The potential of prebiotics to decrease body weight in overweight/obese individuals was suggested by some clinical and animal studies. However, these studies were based on relatively small sample sizes and the precise effects of prebiotic products have not yet been evaluated. Therefore, the present meta-analysis of Randomized Controlled Trials (RCTs) was designed to comprehensively assess the effects of prebiotic products on overweight and obese individuals. METHODS: PubMed, EMBASE and Cochrane Library were searched to identify RCT investigating the effects of prebiotic products on overweight and obese individuals. We calculated the pooled weighted mean difference (WMD) to assess the effects of prebiotic products on Body Mass Index (BMI), body weight, fat mass and inflammatory biomarkers. RESULTS: Twelve RCTs with a total of 535 overweight and obese individuals were enrolled. Compared with placebo, prebiotic products decreased C reactive protein (WMD, -1.06 mg/L; 95%CI, -1.72 to - 0.40; p=0.002), tumour necrosis factor-α(WMD, -0.64 pg/mL; 95%CI, -1.11 to -0.18; p=0.006) and other inflammatory markers, such as interleukin-1ß，lipopolysaccharide (p<0.05); whereas no reductions in BMI (WMD, -0.20 kg/m2; 95%CI, -0.58 to 0.19; p=0.32), body weight (WMD, -0.51 kg; 95%CI, -1.18 to 0.16; p=0.14) and fat mass (WMD, 0.11 kg; 95%CI, -0.04 to 0.25; p=0.15) were observed. CONCLUSION: In the present analysis, comprehensive evidence suggested that prebiotic products did not decrease adiposity parameters (BMI, body weight and body fat mass), but they could decrease the levels of systemic inflammatory biomarkers, implying adherence to prebiotic products might be a promising complementary approach to managing inflammatory states in overweight and obese individuals.

Inhibition of notch enhances the anti-atherosclerotic effects of LXR agonists while reducing fatty liver development in ApoE-deficient mice.

Liver X receptor (LXR) activation can achieve satisfactory anti-atherosclerotic activity, but can also lead to the development of fatty liver and hypertriglyceridemia. In contrast, Notch inhibition can suppress both atherosclerosis and the hepatic accumulation of lipids. In the present study, we sought to assess whether combining LXR ligand agonists (T317) with Notch receptor inhibitors (DAPT) would lead to enhanced anti-atherosclerotic activity while overcoming the adverse events associated with LXR ligand agonist therapy. The impact of the combined T317 + DAPT therapeutic regimen on atherosclerosis, fatty liver development, and hypertriglyceridemia was assessed using ApoE deficient (ApoE-/-) mice. The results of this analysis suggested that DAPT was able to improve the anti-atherosclerotic activity of T317 without reducing the stability of lesion plaques while simultaneously reducing blood lipids in treated ApoE-/- mice. This combination T317 + DAPT treatment was also linked with a significant upregulation of ABCA1 and the stimulation of reverse cholesterol transport (RCT), as well as with decreases in the levels of intercellular cell adhesion molecule-1 (ICAM-1) and p-p65, and with altered M1/M2 macrophage proportions within atherosclerotic plaques. Importantly, DAPT was also able to reduce T317-mediated lipid accumulation within the liver owing to its ability to reduce SREBP-1 expression while simultaneously increasing that of Pi-AMPKα and PPARα. Together, our results suggest that administering Notch receptor inhibitors to ApoE-/- mice may be an effective means of enhancing the anti-atherosclerotic activity of LXR ligand agonists while simultaneously limiting associated fatty liver and hypertriglyceridemia development in these animals.