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.

Adoptive therapy with cytomegalovirus-specific cytotoxic T lymphocytes for refractory cytomegalovirus DNAemia and disease after allogeneic haematopoietic stem cell transplantation.

Cytomegalovirus (CMV) DNAemia and disease are common complications in patients undergoing allogeneic haematopoietic stem cell transplantation (allo-HSCT). Few studies have compared the efficacy and safety of the HSCT donor and third-party CMV-specific cytotoxic T lymphocytes (CMV-CTLs) in the treatment of CMV DNAemia and disease. In this study, we retrospectively compared the efficacy and safety of HSCT donor and third-party CMV-CTLs in patients with refractory CMV DNAemia or disease after allo-HSCT at our centre from January 2017 to September 2021. Fifty-three patients who received CMV-CTL therapy were enrolled, including 40 in the donor group and 13 in the third-party group, and they were adults aged 18 years or older. Within 6 weeks of treatment, 26 (65.0%) and 9 (69.2%) patients achieved complete response in the donor and third-party groups (p = 1.000). The 2-year overall survival was 59.6% (95% CI 46.1%-77.1%) and 53.8% (32.6%-89.1%) in the donor and third-party groups (p = 0.860). Four (10.0%) patients in the donor group and two (15.4%) patients in the third-party group developed acute graft-versus-host disease within 3 months after CMV-CTL infusions. In conclusion, our data suggest that donor and third-party CMV-CTLs have comparable efficacy and safety for refractory CMV DNAemia and disease.

Ultrasound and microbubble-mediated delivery of miR-424-5p has a therapeutic effect in preeclampsia.

OBJECTIVE: To determine the influence of ultrasound/microbubble-mediated miR-424-5p delivery on trophoblast cells and the underlying mechanism. METHODS: Blood pressure and 24-h proteinuria of patients with preeclampsia (PE) were measured as well as the levels of miR-424-5p and amine oxidase copper containing 1 (AOC1) in placental tissues. HTR-8/Svneo and TEV-1 cells were subjected to cell transfection or ultrasonic microbubble transfection for determination of the expression of miR-424-5p, AOC1, ß-catenin and c-Myc as well as cell proliferation, apoptosis, migration and invasiveness. The concentrations of placental growth factor (PLGF), human chorionic gonadotropin (ß-hCG) and tumor necrosis factor-α (TNF-α) were measured in HTR-8/Svneo and TEV-1 cells. RNA immunoprecipitation (RIP) and dual luciferase reporter assay detected the binding of miR-424-5p to AOC1. A PE mouse model was induced by subcutaneous injection of L-NAME, where the influence of ultrasound/microbubble-mediated miR-424-5p delivery was evaluated. RESULTS: miR-424-5p was downregulated while AOC1 was upregulated in the placental tissues from PE patients. Overexpression of miR-424-5p activated Wnt/ß-catenin signaling pathway and promoted the proliferation of HTR-8/Svneo and TEV-1 cells as well as enhanced the migratory and invasive behaviors. AOC1 overexpression partly eliminated the effects of miR-424-5p on HTR-8/Svneo and TEV-1 cells. Ultrasound and microbubble mediated gene delivery enhanced the transfection efficiency of miR-424-5p and further promoted the effects of miR-424-5p in trophoblast cells. Ultrasound/microbubble-mediated miR-424-5p delivery alleviated experimental PE in mice. CONCLUSION: Ultrasound and microbubble-mediated miR-424-5p delivery targets AOC1 and activates Wnt/ß-catenin signaling pathway, thus promoting the aggressive phenotype of trophoblast cells, which indicating that miR-424-5p/AOC1 axis might be involved with PE pathogenesis.

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).

A Pan-Cancer Analysis Reveals the Prognostic and Immunotherapeutic Value of Stanniocalcin-2 (STC2).

Background: Stanniocalcin-2 (STC2) is a secreted glycoprotein which plays an important role in regulating the homeostasis of calcium, glucose homeostasis, and phosphorus metastasis. Accumulating evidence suggests that STC2 is implicated in cancer mechanisms. However, the effects of STC2 on cancer development and progression across pan-cancer are not yet completely known. Methods: Data were downloaded from The Cancer Genome Atlas database to obtain differentially expressed genes significantly associated with prognosis (key genes). A gene was selected for subsequent correlation studies by integrating the significance of prognosis and the time-dependent ROC curve. Gene expression of different tumor types was analyzed based on the UCSC XENA website. Furthermore, our study investigated the correlation of STC2 expression between prognosis, immune cell infiltration, immune checkpoint genes (ICGs), mismatch repair genes (MMRs), tumor mutation burden (TMB), microsatellite instability (MSI), and drug sensitivity in various malignant tumors. Gene set enrichment analysis (GSEA) was conducted for correlated genes of STC2 to explore potential mechanisms. Results: A total of 3,429 differentially expressed genes and 397 prognosis-related genes were identified from the TCGA database. Twenty-six key genes were found by crossing the former and the latter, and the highest risk gene, STC2, was selected for subsequent correlation studies. STC2 had good diagnostic performance for HNSCC, and was closely related to the survival status and clinicopathological stage of HNSCC patients. In pan-cancer analysis, STC2 was upregulated in 20 cancers and downregulated in seven cancers. STC2 overexpression was overall negatively correlated with overall survival, disease-free survival, disease-specific survival, and progress-free survival. STC2 was profoundly correlated with the tumor immune microenvironment, including immune cell infiltration, ICGs, MMRs, TMB, and MSI. Moreover, STC2 was significantly negatively correlated with the sensitivity or resistance of multiple drugs. Conclusion: STC2 was a potential prognostic biomarker for pan-cancer and a new immunotherapy target.

Monocyte to high-density lipoprotein ratio predict long-term clinical outcomes in patients with coronary heart disease: A meta-analysis of 9 studies.

BACKGROUND: A novel inflammation-related biomarker, the monocyte to high-density lipoprotein cholesterol ratio (MHR), had a great relation to the development and prognosis of coronary atherosclerotic heart disease. Current study was to investigate whether the MHR was a potential tool in predicting the mortality and major adverse cardiac events (MACEs) in patients suffering coronary heart disease (CHD) by meta-analysis. METHODS: The Cochrane Library, PubMed, MEDLINE, Scopus, EMBASE, and Web of science were searched for relevant cohort studies published prior to February 10, 2022. The association between MHR and mortality/MACEs was analyzed in patients with CHD. Hazard ratios (HR) with 95% confidence interval (CI) were calculated to estimate the strength of association. RESULTS: In the meta-analysis, a total of 9 studies of 11,345 patients with CHD were included. Compared with the low level of MHR group, the high MHR value was associated with higher long-term MACEs (HR = 1.72 95% CI 1.36-2.18, P < .001), long-term mortality (HR = 1.71, 95% CI 1.10-2.66, P = .017), and in-hospital mortality/MACEs (HR = 2.82, 95% CI = 1.07-7.41, P = .036). CONCLUSIONS: This study suggested that increased MHR value might be associated with higher long-term mortality and long-term MACEs in CHD patients. MHR might serve as a potential prognostic indicator for risk stratification in patients with CHD.

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.

The effect of glucocorticoids on mortality in severe COVID-19 patients: Evidence from 13 studies involving 6612 cases.

BACKGROUND: Since the start of the coronavirus disease 2019 (COVID-19) pandemic, there is an urgent need for effective therapies for patients with COVID-19. In this study, we aimed to assess the therapeutic efficacy of glucocorticoids in severe COVID-19. METHODS: A systematic literature search was performed across PubMed, Web of Science, EMBASE, and the Cochrane Library (up to June 26, 2021). The literature investigated the outcomes of interest were mortality and invasive mechanical ventilation. RESULTS: The search identified 13 studies with 6612 confirmed severe COVID-19 patients. Our meta-analysis found that using glucocorticoids could significantly decrease COVID-19 mortality (hazard ratio (HR) 0.60, 95% confidence interval (CI) 0.45-0.79, P < .001), relative to non-use of glucocorticoids. Meanwhile, using glucocorticoids also could significantly decrease the risk of progression to invasive mechanical ventilation for severe COVID-19 patients (HR = 0.69, 95% CI 0.58-0.83, P < .001). Compared with using dexamethasone (HR = 0.68, 95% CI 0.50-0.92, P = .012), methylprednisolone use had a better therapeutic effect for reducing the mortality of patients (HR = 0.35, 95% CI 0.19-0.64, P = .001). CONCLUSION: The result of this meta-analysis showed that using glucocorticoids could reduce mortality and risk of progression to invasive mechanical ventilation in severe COVID-19 patients.

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.

Sleep Staging Using Plausibility Score: A Novel Feature Selection Method Based on Metric Learning.

As an effective method, feature selection can reduce computational complexity and improve classification performance. A number of criteria exist for feature selection using labeled data, unlabeled data and pairwise constraints, most of which are based on the Euclidean distance. In this paper, we propose a filter method for feature selection with pairwise constraints, aiming to jointly evaluate a feature subset based on metric learning. Two criteria are designed based on the well-known Kullback-Leibler divergence for measuring the difference between must-link constraints and cannot-link constraints that can indicate the feature subset discrimination based on Keep It Simple and Straightforward (KISS) metric learning and Cross-view Quadratic Discriminant Analysis (XQDA) metric learning. To address the challenging feature selection problem, we formulate a sequential search algorithm guided by indicators that are simplified from the proposed criteria. Furthermore, we conducted several experiments on sleep staging based on electroencephalogram (EEG) recordings from the Sleep-EDF Database Expanded. The experimental results demonstrate the effectiveness of the proposed method compared with nine representative feature selection methods. On the data set from healthy volunteers and the data set from volunteers that had mild difficulty falling asleep, the classification average accuracies achieve 97.66% and 93.57% by using the proposed method, respectively.

Sleep staging algorithm based on multichannel data adding and multifeature screening.

BACKGROUND: Sleep staging is an important basis of sleep research, which is closely related to both normal sleep physiology and sleep disorders. Many studies have reported various sleep staging algorithms of which the framework generally consists of three parts: signal preprocessing, feature extraction and classification. However, there are few studies on the superposition of signals and feature screening for sleep staging. OBJECTIVE: The objectives were to (1) Analyze the effective signal enhancement based on the superposition of homologous and heterogeneous signals, (2) Find a better way to use multichannel signals, (3) Study a systematic method of feature screening for sleep staging, and (4) Improve the performance of automatic sleep staging. METHODS: In this paper, a novel method of signal preprocessing and feature screening was proposed. In the signal preprocessing, multi-channel signal superposition was applied to improve the effective information contained in the original signal. In the feature screening, 62 features were initially selected including the time-domain features, frequency-domain features and nonlinear features, and a ReliefF algorithm was employed to select 14 features highly correlated to sleep stages from the former 62 features. Then, Pearson correlation coefficients were used to remove 2 redundant features from the 14 features to eventually obtain 12 features. Next, with the aforementioned signal preprocessing method, the 12 selected features and a support vector machine (SVM) classifier were used for sleep staging based on thirty recordings. RESULTS: Comparing the performance of sleep staging using different single-channel signals and different multi-channel superposition signals, we found that the best performance was obtained while using the superposition of two electroencephalogram (EEG) signals. The overall accuracies of sleep staging with 2-6 classes obtained by superposing the two EEG signals reach 98.28%, 95.50%, 94.28%, 93.08% and 92.34%, respectively, and the kappa coefficient of sleep staging with 6 classes reaches 84.07%. CONCLUSIONS: Among the proposed sleep staging methods of using single-channel signal and multi-channel signal superposition, the best performance and consistency were obtained while using the superposition of two electroencephalogram (EEG) signals. The multichannel signal superposition method pointed out a valuable direction for improving the performance of automatic sleep staging in both theoretical research and engineering applications, and the proposed systematical feature screening method opened up a reasonable pathway for better selecting type and number of features for sleep staging.

Effects of erythropoietin on neonatal hypoxia-ischemia brain injury in rat model.

BACKGROUND: Hypoxic-ischemic (HI) injury to the developing brain remains a major cause of morbidity. To date, few therapeutic strategies could provide complete neuroprotection. Erythropoietin (EPO) has been shown to be beneficial in several models of neonatal HI. This study examines the effect of treatment with erythropoietin on postnatal day 2 (P2) rats introduced with HI injury. METHOD: Rats at P2 were randomized into four groups: sham, bilateral carotid artery occlusion (BCAO), BCAO + early EPO, and BCAO + late EPO groups. Pups in each group were injected with either saline or EPO (5000U/kg) intraperitoneally once at immediately (early) or 48h (late) after HI induction. Body weight was assessed at P2 before and day 7 after HI. Mortality Rate was assessed at 24h, 48h and 72h after HI and brain water content was assessed at 72h. Brain weight and expression of myelin basic protein (MBP) were assessed at day 7 and day 14. At day 31 to 35 following HI insult, neurological behavior function was assessed via Morris water maze (MWM) test. RESULT: HI cause significant higher mortality in male than in female (P=0.0445). Among the surviving animal, HI affect significantly the body growth, brain growth, MBP expression, and neurological behavior. EPO treatments at both early and late time points significantly benefit the rats in injury recovery, in which they promoted weight gains, reduced brain edema, as well as improved spatial learning ability and memory. CONCLUSION: We demonstrated a single dose of EPO at 5000U/kg immediately or 48h after HI injury had significant benefit for the P2 rats in injury recovery, and there was no adverse effect associated with either EPO treatment.

Adenosine triphosphate postconditioning is associated with better preserved global and regional cardiac function during myocardial ischemia and reperfusion: a speckle tracking imaging-based echocardiologic study.

INTRODUCTION: Effects of ischemic postconditioning (IPostC) and adenosine triphosphate (ATP)-mediated pharmacologic postconditioning (ATP-PPostC) on cardiac function were evaluated by speckle tracking imaging (STI)-based echocardiography. AIMS: A myocardial I/R model was induced in rabbits by reversible ligation of the left ventricular branch of coronary artery. Rabbits were randomized into three groups: ischemia and reperfusion (IR) (no further intervention), IPostC, and ATP-PPostC groups. Cardiac function was evaluated by conventional and STI-based echocardiography. Myocardial necrosis, apoptosis, and myocardial mRNAs of apoptosis-related proteins (Bcl-2 and Bax) were evaluated. RESULTS: Speckle tracking imaging (STI)-based echocardiography revealed that IPostC and ATP-PPostC were associated with better preserved global and regional cardiac function, as indicated by significantly increased GLSrsys, GLSrd, GLSsys, SrLsys, SrLd, and SLsys in both groups (all P<.5). Subsequent pathologic studies indicate that the percentage of necrotic myocardium and permillage of apoptotic cells were significantly lower in the IPostC and ATP-PPostC groups than in the IR group (all P<.05). Moreover, both IPostC and ATP-PPostC were associated with increased Bcl-2 mRNA levels and reduced Bax mRNA levels. CONCLUSIONS: IPostC and ATP-PPostC may exert cardioprotective functions by better preservation of cardiac function during the I/R process and at least partly via attenuation of myocardial apoptosis.