Association between copper intake and essential hypertension: dual evidence from Mendelian randomization analysis and the NHANES database.

Background: Although previous studies have identified an association between trace elements and essential hypertension, the specific trace elements involved and the mechanisms of their association remain unclear. This study aimed to elucidate the relationship between various human trace elements and essential hypertension, thereby addressing existing gaps in the research. Methods: This study employed two-sample, multivariate, and inverse Mendelian randomization (MR) analyses to investigate the causal relationship between 15 human trace elements as exposure factors and essential hypertension as the outcome. The analysis revealed a statistically significant association between copper intake and essential hypertension. Further validation was conducted using logistic regression models based on data from the National Health and Nutrition Examination Survey (NHANES). Results: Eighteen trace elements were initially identified through searches in the GWAS database and PubMed. After screening, 15 trace elements were selected as potential exposure factors. MR analysis, utilizing the 2021 genome-wide dataset for essential hypertension, identified copper as a risk factor, showing a positive association with hypertension. Subsequent logistic regression analyses based on NHANES data further confirmed a significant association between dietary copper intake and the risk of essential hypertension, except for the 0.80-1.08 mg/d group in model 3 (p < 0.05). Restricted cubic spline (RCS) analysis indicated a nonlinear relationship between copper intake and the risk of developing essential hypertension. Conclusion: This study demonstrates a significant association between copper intake and the development of essential hypertension. The findings suggest that higher copper intake is linked to an increased risk of hypertension, underscoring the need to monitor copper intake levels in the prevention and management of this condition.

Huanglian Jiedu Decoction enhances the stability of atherosclerotic plaques through SLC2A1-mediated efferocytosis.

BACKGROUND: Atherosclerotic (AS) plaques require a dense necrotic core and a robust fibrous cap to maintain stability. While previous studies have indicated that the traditional Chinese medicine Huang Lian Jie Du Decoction (HLJDD) possesses the capability to stabilize AS plaques, the underlying mechanisms remain obscure. This study aims to delve deeper into the potential mechanisms by which HLJDD improves AS through an integrated research strategy. METHODS: Leveraging an AS model in ApoE-/- mice exposed to a high-fat diet (HFD), we scrutinized the therapeutic effects of HLJDD using microscopic observations, oil red O staining, HE staining and Masson staining. Employing comprehensive techniques of network pharmacology, bioinformatics, and molecular docking, we elucidated the mechanism by which HLJDD stabilizes AS plaques. In vitro experiments, utilizing ox-LDL-induced macrophages and apoptotic vascular smooth muscle cells (VSMCs), assessed the impact of HLJDD on efferocytosis and the role of SLC2A1. RESULTS: In vivo experiments showcased the efficacy of HLJDD in reducing the quantity of aortic plaques, diminishing lipid deposition, and enhancing plaque stability in AS mice. Employing network pharmacology and machine learning, we pinpointed SLC2A1 as a crucial regulatory target. Molecular docking further validated the binding of HLJDD components with SLC2A1. The experiments demonstrated a dose-dependent upregulation in SLC2A1 expression by HLJDD, amplifying efferocytosis. Importantly, this effect was reversed by the SLC2A1 inhibitor STF-31, highlighting the pivotal role of SLC2A1 as a target. CONCLUSION: The HLJDD can modulate macrophage efferocytosis by enhancing the expression levels of SLC2A1, thereby improving the stability of atherosclerotic plaques.

Mechanisms of QingRe HuoXue Formula in atherosclerosis Treatment: An integrated approach using Bioinformatics, Machine Learning, and experimental validation.

BACKGROUND: Atherosclerosis (AS) is the main cause of coronary heart disease, cerebral infarction, and peripheral vascular disease. QingRe HuoXue Formula (QRHXF), a common prescription of traditional Chinese medicine, has a definite effect on the clinical treatment of AS, but its mechanism remains to be further explored. PURPOSE: The current study aimed to demonstrate the effectiveness of the QRHXF in the treatment of AS and further reveal its potential pharmacological mechanisms. METHODS: Explore the potential mechanisms of QRHXF in treating AS through network pharmacology, machine learning, transcriptome analysis, and molecular docking, then validate them through animal experiments and PCR experiments. RESULTS: The results indicate that through network pharmacology and machine learning methods, 10 genes including COL1A1 and CCR7 have been identified as potential candidate genes for QRHXF treatment of atherosclerosis. Molecular docking indicates that the key active compounds of QRHXF have good binding affinity with the predicted genes. Two key genes, COL1A1 and CCR7, were identified through transcriptome sequencing analysis of the aortic tissue of APOE-/- mice in the AS model. Finally, the animal and PCR experiment found that QRHXF can effectively reduce the formation of aortic plaques in APOE-/- mice of the AS model, lower blood lipid levels in mice, and upregulate the mRNA expression level of COL1A1, promoting the formation of fibrosis within plaques. CONCLUSIONS: We revealed the inflammatory and immune pathways underlying QRHXF treatment for AS, and verified through transcriptome sequencing and experiments that QRHXF can promote the expression of COL1A1, thereby increasing the stability of AS plaques.

Major vault protein directly enhances adaptive immunity induced by Influenza A virus or indirectly through innate immunity.

As we previously revealed, major vault protein (MVP) is a virus-induced host factor, and its expression is crucial for innate immune responses. Nevertheless, the function of MVP in adaptive immunity is poorly known. Here, we demonstrate that Mvp knockout mice had attenuated antibody responses and reduced survival after rechallenge with homologous influenza A virus (IAV) relative to wild-type mice. Analysis of B cell populations showed that MVP promoted germinal center (GC) responses to develop optimal antiviral humoral immunity. Although MVP-deficient T cells and dendritic cells (DCs) were not intrinsically damaged, MVP promoted activating effector T cells and T follicular helper responses and regulated specific DC subsets. These findings suggest that MVP directs an effective adaptive immune response against IAV by directly engaging in GC reactions or indirectly augmenting cellular immunity via innate immune pathways.

Screening for immune-related biomarkers associated with myasthenia gravis and dilated cardiomyopathy based on bioinformatics analysis and machine learning.

Background: We aim to investigate genes associated with myasthenia gravis (MG), specifically those potentially implicated in the pathogenesis of dilated cardiomyopathy (DCM). Additionally, we seek to identify potential biomarkers for diagnosing myasthenia gravis co-occurring with DCM. Methods: We obtained two expression profiling datasets related to DCM and MG from the Gene Expression Omnibus (GEO). Subsequently, we conducted differential gene expression analysis and weighted gene co-expression network analysis (WGCNA) on these datasets. The genes exhibiting differential expression common to both DCM and MG were employed for protein-protein interaction (PPI), Gene Ontology (GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Additionally, machine learning techniques were employed to identify potential biomarkers and develop a diagnostic nomogram for predicting MG-associated DCM. Subsequently, the machine learning results underwent validation using an external dataset. Finally, gene set enrichment analysis (GSEA) and machine algorithm analysis were conducted on pivotal model genes to further elucidate their potential mechanisms in MG-associated DCM. Results: In our analysis of both DCM and MG datasets, we identified 2641 critical module genes and 11 differentially expressed genes shared between the two conditions. Enrichment analysis disclosed that these 11 genes primarily pertain to inflammation and immune regulation. Connectivity map (CMAP) analysis pinpointed SB-216763 as a potential drug for DCM treatment. The results from machine learning indicated the substantial diagnostic value of midline 1 interacting protein1 (MID1IP1) and PI3K-interacting protein 1 (PIK3IP1) in MG-associated DCM. These two hub genes were chosen as candidate biomarkers and employed to formulate a diagnostic nomogram with optimal diagnostic performance through machine learning. Simultaneously, single-gene GSEA results and immune cell infiltration analysis unveiled immune dysregulation in both DCM and MG, with MID1IP1 and PIK3IP1 showing significant associations with invasive immune cells. Conclusion: We have elucidated the inflammatory and immune pathways associated with MG-related DCM and formulated a diagnostic nomogram for DCM utilizing MID1IP1/PIK3IP1. This contribution offers novel insights for prospective diagnostic approaches and therapeutic interventions in the context of MG coexisting with DCM.

Epidemiological and Clinical Characteristics of Neonatal Ureaplasma urealyticum Infection.

Purpose: To understand the epidemiology and clinical features of Ureaplasma urealyticum (UU) infection in hospitalized neonates due to vertical transmission from mother to child. Methods: Respiratory secretions were collected from neonates hospitalized in the neonatology department of the Maternal and Child Health Hospital of Hubei Province from July 2020 to June 2022, and PCR was used to detect UU-DNA in respiratory secretions. The neonates were divided into UU-positive and UU-negative groups, the epidemiological and clinical characteristics of two groups, were statistically analyzed. Results: A total of 7257 hospitalized neonates were included in this study, of whom 561 were UU positive and 6696 were UU negative, with a UU detection rate of 7.73%. The detection rate among female neonates was higher than male neonates, and the highest detection rate was found in the period from 1-7 days after birth; the detection rate was highest in spring and fall, and the lowest in winter, but the overall difference was not statistically significant (P>0.05). Compared with the UU-negative group, neonates in the UU-positive group were more likely to be preterm, have a lower birth weight, be delivered vaginally, and have maternal preterm rupture of membranes. In addition, neonates in the UU-positive group were more likely to be co-infected with pathogens and to have complications related to UU infections, which were all statistically significant (P<0.05). Conclusion: Neonatal UU infections are detected more frequently in female infants, with the highest detection rate occurring in 1-7 days after birth, and the most prevalent periods for infection being spring and fall. Vaginal delivery and premature rupture of membranes may lead to an increased risk of vertical UU transmission from mother to child, and UU infection is strongly associated with preterm labor, low birth weight, pathogen co-infection, and related complications.

An intranasal influenza virus vector vaccine protects against Helicobacter pylori in mice.

Helicobacter pylori is a human pathogen that infects almost half of the population. Antibiotic resistance in H. pylori threatens health and increases the demand for prophylactic and therapeutic vaccines. Traditional oral vaccine research faces considerable challenges because of the epithelial barrier, potential enterotoxicity of adjuvants, and the challenging conditions of the gastric environment. We developed an intranasal influenza A virus (IAV) vector vaccine based on two live attenuated influenza viruses with modified acidic polymerase protein (PA) genes encoding the A subunit of H. pylori neutrophil-activating protein (NapA), named IAV-NapA, including influenza virus A/WSN/33 (WSN)-NapA and A/Puerto Rico/8/34 (PR8)-NapA. These recombinant influenza viruses were highly attenuated and exhibited strong immunogenicity in mice. Vaccination with IAV-NapA induced antigen-specific humoral and mucosal immune responses while stimulating robust Th1 and Th17 cell immune responses in mice. Our findings suggest that prophylactic and therapeutic vaccination with influenza virus vector vaccines significantly reduces colonization of H. pylori and inflammation in the stomach of mice.IMPORTANCEHelicobacter pylori is the most common cause of chronic gastritis and leads to severe gastroduodenal pathology in some patients. Many studies have shown that Th1 and Th17 cellular and gastric mucosal immune responses are critical in reducing H. pylori load. IAV vector vaccines can stimulate these immune responses while overcoming potential adjuvant toxicity and antigen dosing issues. To date, no studies have demonstrated the role of live attenuated IAV vector vaccines in preventing and treating H. pylori infection. Our work indicates that vaccination with IAV-NapA induces antigen-specific humoral, cellular, and mucosal immunity, producing a protective and therapeutic effect against H. pylori infection in BALB/c mice. This undescribed H. pylori vaccination approach may provide valuable information for developing vaccines against H. pylori infection.

Association between sexual frequency and all-cause mortality in young and middle-aged patients with hypertension: a cohort study of patient data from the National Health and Nutrition Examination Survey 2005-2014.

BACKGROUND: Sexual activity appears to have protective effects on overall and cardiovascular health. AIM: We hypothesized that decreased sexual frequency would be an early predictor of all-cause mortality in young and middle-aged patients (20 to 59 years old) with hypertension. METHODS: A total of 4565 patients with hypertension (55.6% men; mean [SD] age 40.60 [10.81] years) who had completed a sexual behavior questionnaire were enrolled from the National Health and Nutrition Examination Survey of 2005 to 2014. Cox proportional hazards models and Kaplan-Meier survival curves were used to evaluate the relationship between sexual frequency and all-cause mortality. OUTCOMES: The outcome measure for this study is the relationship between sexual frequency and all-cause mortality in young and middle-aged patients with hypertension. RESULTS: During the 68-month median follow-up period, 109 (2.39%) patients died from any cause. After full adjustment for potential confounders, sexual frequency was an independent predictive factor for all-cause mortality in young and middle-aged patients with hypertension. A marital status difference was identified in the subgroup analysis: among patients with a sexual frequency of <12 times/year, only married patients had higher risks of all-cause mortality than the 12-51 times/year group (HR, 0.476, 95% CI, 0.235-0.963, P < .05) and > 51 (HR, 0.452, 95% CI, 0.213-0.961, P < .05) times/year groups. The association of sexual frequency and all-cause mortality was nonlinear. CLINICAL IMPLICATIONS: Increased frequency of sexual activity may have protective effects on overall health and quality of life in patients with hypertension. STRENGTHS AND LIMITATIONS: To our knowledge this is the first observational investigation performed to evaluate the correlation between sexual frequency and all-cause mortality in patients with hypertension. A limitation of the study is that the participants in our analysis were between the ages of 20 and 59 years, and this patient sample may not reflect possible outcomes for patients of other age groups. CONCLUSION: The association between lower frequency of sexual intercourse and greater all-cause mortality was significant in young and middle-aged patients with hypertension in the United States.

Major vault protein regulates tumor-associated macrophage polarization through interaction with signal transducer and activator of transcription 6.

Tumor-associated macrophages (TAMs) are critical in the tumor microenvironment (TME) of hepatocellular carcinoma (HCC). Major vault protein (MVP) mediates multidrug resistance, cell growth and development, and viral immunity. However, the relationship between MVP and TAMs polarization has not been clarified in HCC. We found that MVP significantly increased M2-TAMs infiltration levels in tumor tissues of HCC patients. MVP promoted HCC proliferation, metastasis, and invasion by regulating M2 polarization in vivo and in vitro. Mechanistically, MVP associated with signal transducer and activator of transcription 6 (STAT6) and enhanced STAT6 phosphorylation. STAT6 translocated from the cytosol to the nucleus and regulated M2 macrophage-associated gene transcription. These findings suggest that MVP modulates the macrophage M2 transcriptional program, revealing its potential role in the TAMs of TME.

Intervention of Compound Xueshuantong Capsule on the incidence of heart failure in patients with acute myocardial infarction after PCI based on the combination of disease and syndrome: A multi-center, randomized, double-blind, controlled trial.

BACKGROUND: Heart failure (HF), manifested as a severe or end stage of various cardiac diseases, is characterized by increased incidence, mortality, re-hospitalization, and economic burden. Myocardial infarction (MI) is one of the most common and important causes of HF. Since 2005, acute MI (AMI)-associated mortality in China has been on the rise, and MI accounts for 23.1% of the causes of HF. Traditional Chinese medicine (TCM) has the unique advantages of controlling angina pectoris and HF symptoms, and improving patients' quality of life. Compound Xueshuantong Capsule (CXSTC), also named as Fufang Xueshuantong Capsule, has the effect of increasing cardiac output and protecting myocardial function. In this trial, we aim to investigate the efficacy and safety of CXSTC in the prophylactic treatment of post-infarction HF and attempt to provide a clinical evidence-based basis for the prophylactic treatment of HF after AMI using TCM. METHODS: This will be a multi-center, randomized, double-blind, placebo-parallel controlled trial. A total of 300 patients diagnosed with AMI and undergoing percutaneous coronary intervention within 12 hours of diagnosis will be randomized 1:1 into 2 groups: the control group that will be administered conventional Western medicine plus placebo and the trial group that will be administered XST along with the conventional Western medicine. The duration of treatment will be 3 months and the follow-up will be up to 6 months for both groups. The main efficacy indicator is the incidence of HF. The secondary efficacy indicators are cardiac function classification, 6-minute walk test score, TCM syndrome score, survival quality score, brain natriuretic peptide level, ultrasensitive C-reactive protein level, and cardiac ultrasound result. Data will be collected to analyze the underlying mechanisms by using IBM SPSS 23.0 software. DISCUSSION: By investigating the efficacy and safety of CXSTC, this study will provide a clinical evidence base for the use of TCM in the prophylactic treatment of post-infarction HF.

Study on the Mechanism of Huanglian Jiedu Decoction in Treating Dyslipidemia Based on Network Pharmacology.

Objective: This study aimed to determine the active ingredients of Huanglian Jiedu decoction (HLJDD) and the targets for treating dyslipidemia through network pharmacology to facilitate further application of HJJDD in the treatment of dyslipidemia. Methods: Potential drug targets for dyslipidemia were identified with a protein-protein interaction network. Gene ontology (GO) enrichment analysis and KEGG pathway analysis were performed to elucidate the biological function and major pathways involved in the HLJDD-mediated treatment of dyslipidemia. Results: This approach revealed 22 components, 234 targets of HLJDD, and 221 targets of dyslipidemia. There were 14 components and 31 common targets between HLJDD and dyslipidemia treatment. GO enrichment analysis showed that these targets were mainly associated with the response to DNA-binding transcription factor activity, lipid localization and storage, reactive oxygen species metabolic process, and inflammatory response. The results of KEGG analysis indicated that the AGE-RAGE, NF-κB, HIF-1, IL-17, TNF, FoxO, and PPAR signalling pathways were enriched in the antidyslipidemic action of HLJDD. Conclusion: This study expounded the pharmacological actions and molecular mechanisms of HLJDD in treating dyslipidemia from a holistic perspective, which may provide a scientific basis for the clinical application of HLJDD.

Puerarin Alleviates LPS-Induced H9C2 Cell Injury by Inducing Mitochondrial Autophagy.

ABSTRACT: Sepsis leads to the damage of multiple organs, and thereby adversely affects the cardiovascular system. At present, no effective method has been found to treat myocardial injury caused by sepsis. Although Puerarin was reported to attenuate lipopolysaccharide (LPS)-induced mitochondrial injury in H9C2 cells, the effects of Puerarin in sepsis-induced myocardial injury remain unclear. In this study, H9C2 cells were stimulated with LPS, CCK-8 assays were performed to assess cell viability, and flow cytometry and TUNEL staining were used to assess cell apoptosis. Levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), and enzyme activity were investigated using commercial kits. Reactive oxygen species (ROS) levels in H9C2 cells were detected by flow cytometry. Autophagosomes in the mitochondria of H9C2 cells were observed by transmission electron microscope, and protein expression was assessed by western blotting. Furthermore, in vivo experiments were applied to test the function of Puerarin in sepsis. We found that Puerarin significantly reversed LPS-induced decreases in H9C2 cell viability by inhibiting apoptosis. The ROS levels in H9C2 cells were significantly upregulated by LPS, but that effect was markedly reduced by Puerarin. In addition, Puerarin attenuated LPS-induced mitochondrial injury in H9C2 cells by regulating dynamin-related protein 1 (Drp1) and mitofusin 1 (MFN1). LPS decreased enzyme activity and reduced the levels of ADP, ALP, and AMP in mitochondria; however, those effects were reversed by Puerarin. Puerarin and Torin1 reversed LPS-induced inhibition of autophagy in the mitochondria of H9C2 cells via mediation of p62, LC3B, Pink1, and Parkin. Puerarin notably inhibited the progression of sepsis in vivo . Puerarin inhibited LPS-induced H9C2 cell injury by inducing mitochondrial autophagy, which acts as a mechanism for preventing myocardial injury caused by sepsis.

Effects of Home-Based Baduanjin Exercise on Left Ventricular Remodeling in Patients With Acute Anterior ST-Segment Elevation Myocardial Infarction: Study Protocol for a Randomized Controlled Trial.

BACKGROUND: Left ventricular (LV) remodeling after ST-segment elevation myocardial infarction (STEMI) is a major pathological basis associated with heart failure and increased mortality. Exercise-based cardiac rehabilitation has been verified to significantly improve prognosis and quality of life. As a traditional Chinese Qigong, Baduanjin exercise has effectively alleviated adverse LV remodeling in STEMI patients. Despite this, participation in exercise rehabilitation remains low, and home-based exercise rehabilitation may be an alternative approach. Besides, anterior STEMI is reported to have higher risk of adverse LV remodeling. However, the efficiency regarding home-based Baduanjin exercise on LV remodeling in anterior STEMI patients remains uncertain currently. METHODS/DESIGN: A single-blind, randomized controlled clinical trial was conducted to explore the efficacy and safety of home-based Baduanjin exercise in anterior STEMI patients compared with moderate intensity aerobic walking. A total of 114 participants were assigned randomly to the Baduanjin group or walking control group at a 1:1 ratio. Eligible participants practiced Baduanjin or walking exercise (5 times a week) for 12 weeks, and then followed up for another 12 weeks. The primary outcome is a relative change in the LV end-diastolic volume. The secondary outcomes include the plasma levels of hypersensitive C-reactive protein and interleukin 6, health-related quality of life measured by EQ-5D-5L, LV ejection fraction, patient health questionnaire-9, generalized anxiety disorder screener-7, short physical performance battery score, and clinical endpoint events. The proportion of circulating regulatory T-cells were also assessed. Adverse events were recorded throughout the trial for safety evaluation. Data were be analyzed by researchers blinded to the treatment allocation. DISCUSSION: This study provided powerful evidence for the use of home-based Baduanjin exercise in anterior STEMI patients in alleviating LV remodeling and improving clinical outcomes. TRIAL REGISTRATION: The Research Ethics Committee of the First Affiliated Hospital of Guangzhou University of Chinese Medicine has approved this study (ZYYECK[2020]045). Written informed consent of patients were required. This trial is registered in the Chinese Clinical Trial Registry (ChiCTR2100047298). DISSEMINATION: Our results will be published in peer-reviewed journals and disseminated through academic conferences and the Internet.

Huang-Lian-Jie-Du Decoction Attenuates Atherosclerosis and Increases Plaque Stability in High-Fat Diet-Induced ApoE-/- Mice by Inhibiting M1 Macrophage Polarization and Promoting M2 Macrophage Polarization.

Macrophage polarization plays a vital impact in triggering atherosclerosis (AS) progression and regression. Huang-Lian-Jie-Du Decoction (HLJDD), a famous traditional Chinese decoction, displays notable anti-inflammatory and lipid-lowering effects in different animal models. However, its effects and mechanisms on AS have not been clearly defined. We determined whether HLJDD attenuated atherosclerosis and plaques vulnerability by regulating macrophage polarization in ApoE-/- mice induced by high-fat diet (HFD). Furthermore, we investigated the effects of HLJDD on macrophage polarization in oxidized low-density lipoprotein (ox-LDL) induced RAW264.7 cells. For in vivo assay, compared with the model group, HLJDD ameliorated lipid metabolism, with significantly decreased levels of serum triglyceride, total cholesterol (CHOL), and lipid density lipoprotein. HLJDD suppressed serum tumor necrosis factor α (TNF-α) and IL-1ß levels with increased serum IL-10 level, and inhibited mRNA level of NLRP3 inflammasome in carotid tissues. HLJDD enhanced carotid lesion stability by decreasing macrophage infiltration together with increased expression of collagen fibers and α-SMA. Moreover, HLJDD inhibited M1 macrophage polarization, which decreased the expression and mRNA levels of M1 markers [inducible nitric oxide synthase (iNOS) and CD86]. HLJDD enhanced alternatively activated macrophage (M2) activation, which increased the expression and mRNA levels of M2 markers (Arg-1 and CD163). For in vitro assay, HLJDD inhibited foam cell formation in RAW264.7 macrophages disturbed by ox-LDL. Besides, groups with ox-LDL plus HLJDD drug had a lower expression of CD86 and mRNA levels of iNOS, CD86, and IL-1ß, but higher expression of CD163 and mRNA levels of Arg-1, CD163, and IL-10 than ox-LDL group. Collectively, our results revealed that HLJDD alleviated atherosclerosis and promoted plaque stability by suppressing M1 polarization and enhancing M2 polarization.

A predictive model for dilated cardiomyopathy with pulmonary hypertension.

AIMS: Dilated cardiomyopathy (DCM) is defined as a serious cardiac disorder caused by the presence of left ventricular dilatation and contractile dysfunction in the absence of severe coronary artery disease and abnormal loading conditions. The incidence of cardiac death is markedly higher in patients with DCM with pulmonary hypertension (PH) than in DCM patients without PH. No previous studies have constructed a predictive model to predict PH in patients with DCM. METHODS: Data from 218 DCM patients (68.3% man; mean age 57.33) were collected. Patients were divided into low, intermediate and high PH-risk groups based on the echocardiographic assessment at the tricuspid regurgitation peak velocity (TRV) in conjunction with the presence of echocardiographic signs from at least two different categories. Basic information, vital signs, comorbidities and biochemical data of each patient were determined. The impact of each parameter on PH probability was analysed by univariable and multivariable analyses, the data from which were employed to establish a predictive model. Finally, the discriminability, calibration ability and clinical efficacy of the model were verified for both the modelling group and the external validation group. RESULTS: We successfully applied a history of chronic obstructive pulmonary disease (COPD) or chronic bronchitis, systolic murmur (SM) at the tricuspid area, SM at the apex and brain natriuretic peptide (BNP) level to establish a model for predicting PH probability in DCM. The model was proven to have high accuracy and good discriminability (area under the receiver operating characteristic curve 0.889), calibration ability and clinical application value. CONCLUSIONS: A model for predicting PH probability in patients with DCM was successfully established. The new model is reliable for predicting PH probability in DCM and has good clinical applicability.

Integrating Network Pharmacology and Experimental Validation to Decipher the Mechanism of Action of Huanglian Jiedu Decoction in Treating Atherosclerosis.

BACKGROUND: This study used network pharmacology, molecular docking and experimental validation to assess the effects of Huanglian Jiedu Decoction (HLJDD) on atherosclerosis (AS). METHODS: The components and targets of HLJDD were analyzed using the Traditional Chinese Medicine Systems Pharmacology database, and information on the genes associated with AS was retrieved from the GeneCards and OMIM platforms. Protein-protein interactions were analyzed using the STRING platform. A component-target-disease network was constructed using Cytoscape. GO and KEGG analyses were performed to identify molecular biological processes and signaling pathways, and the predictions were verified experimentally. Molecular docking was conducted with ChemOffice software, PyMOL software and Vina to verify the correlation of targets and compounds. RESULTS: HLJDD contained 31 active compounds, with quercetin, kaempferol, moupinamide and 5-hydroxy-7-methoxy-2-(3,4,5-trimethoxyphenyl)chromone as the core compounds. The most important biotargets of HLJDD in AS were ICAM-1, CD31 and RAM-11. The molecular docking results showed that the molecular docking interaction energy between the 3 key targets and the 4 high-degree components were much less than -5 kJ∙mol-1. The experimental validation results showed that HLJDD might treat AS mainly by reducing TC, TG and LDL-C and increasing HDL-C, upregulating CD31 expression, reducing ICAM-1 and RAM-11 expression, and downregulating inflammatory factors, including CRP, IL-6 and TNF-α. These results support the network pharmacology data and demonstrate that HLJDD affects the expression of core genes and alters the leukocyte transendothelial migration signaling pathway. CONCLUSION: Based on network pharmacology and experimental validation, our study indicated that HLJDD exerted anti-AS effect through upregulating CD31 expression and reducing the expression of ICAM-1 and RAM-11. HLJDD may be a potential therapeutic drug to the prevention of AS.

Hepatitis B Surface Antigen Suppresses the Activation of Nuclear Factor Kappa B Pathway via Interaction With the TAK1-TAB2 Complex.

Chronic hepatitis B is a major health problem worldwide, with more than 250 million chronic carriers. Hepatitis B virus interferes with the host innate immune system so as to evade elimination via almost all of its constituent proteins; nevertheless, the function of HBsAg with respect to immune escape remains unclear. This study aimed to determine the role HBsAg plays in assisting HBV to escape from immune responses. We found that HBsAg suppressed the activation of the nuclear factor kappa B (NF-кB) pathway, leading to downregulation of innate immune responses. HBsAg interacted with TAK1 and TAB2 specifically, inhibiting the phosphorylation and polyubiquitination of TAK1 and the K63-linked polyubiquitination of TAB2. Autophagy is a major catabolic process participating in many cellular processes, including the life cycle of HBV. We found that HBsAg promoted the autophagic degradation of TAK1 and TAB2 via the formation of complexes with TAK1 and TAB2, resulting in suppression of the NF-κB pathway. The expression of TAK1, TAB2, and the translocation of NF-κB inversely correlated with HBsAg levels in clinical liver tissues. Taken together, our findings suggest a novel mechanism by which HBsAg interacts with TAK1-TAB2 complex and suppresses the activation of NF-κB signaling pathway via reduction of the post-translational modifications and autophagic degradation.

Can network pharmacology identify the anti-virus and anti- inflammatory activities of Shuanghuanglian oral liquid used in Chinese medicine for respiratory tract infection?

INTRODUCTION: Shuanghuanglian (SHL) oral liquid is a well-known traditional Chinese medicine preparation administered for respiratory tract infections in China. However, the underlying pharmacological mechanisms remain unclear. The present study aims to determine the potential pharmacological mechanisms of SHL oral liquid based on network pharmacology. METHODS: Network pharmacology-based strategy including collection and analysis of putative compounds and target genes, network construction, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and Gene Ontology (GO) enrichment, identification of key compounds and target genes, and molecule docking was performed in this study. RESULTS: A total of 82 bioactive compounds and 226 putative target genes of SHL oral liquid were collected. Of note, 28 hub target genes including 4 major hub target genes: estrogen receptor 1 (ESR1), nuclear receptor coactivator 2 (NCOA2), nuclear receptor coactivator 1 (NCOA1), androgen receptor (AR) and 5 key compounds (quercetin, luteolin, baicalein, kaempferol and wogonin) were identified based on network analysis. The hub target genes mainly enriched in pathways including PI3K-Akt signaling pathway, human cytomegalovirus infection, and human papillomavirus infection, which could be the underlying pharmacological mechanisms of SHL oral liquid for treating diseases. Moreover, the key compounds had great molecule docking binding affinity with the major hub target genes. CONCLUSION: Using network pharmacology analysis, SHL oral liquid was found to contain anti-virus, anti-inflammatory, and "multi-compounds and multi-targets" with therapeutic actions. These findings may provide a valuable direction for further clinical application and research.

Chinese Herbal Medicines for Restenosis After Percutaneous Coronary Intervention: A Meta-Analysis of Randomized Controlled Trials.

Objectives: This study evaluates the efficacy of Chinese herbal medicines after percutaneous coronary intervention (PCI). Background: PCI is the primary treatment for coronary atherosclerotic heart disease (CHD). However, many patients experience restenosis within 6 months after PCI. Chinese herbal medicines are widely used in patients after PCI. Clinical studies have found that Chinese herbal medicines may prevent restenosis. Methods: Eight databases were searched for randomized controlled trials (RCTs) investigating the use of Chinese herbal medicines after PCI. The search period was from the date of database inception to June 2017. We used the Cochrane risk of bias tool to estimate the methodological quality of the studies. The primary outcome was the restenosis rate, and secondary outcomes were the angina recurrence rate and major adverse cardiac events (MACEs). Data were analyzed with RevMan 5.3, and the quality of evidence was assessed with the GRAD approach. Results: Eleven RCTs with a total of 1,383 patients were included. The major outcome was the restenosis rate, and the results showed a significant effect of Chinese herbal medicines on reduction in the rate of restenosis (risk ratio [RR] = 0.46, 95% CI: 0.35-0.60, p < 0.00001, I2 = 0%). Chinese herbal medicine treatment also decreased the angina recurrence rate (RR = 0.41, 95% CI: 0.29-0.57, p < 0.00001, I2 = 0%). The results revealed a lower rate of MACEs in the Chinese medicine group than in the control group (RR = 0.49, 95% CI: 0.34-0.71, p = 0.0001, I2 = 0%). We evaluated the quality of evidence with the GRADE system; the quality of evidence for the restenosis rate and angina was low, and the quality of evidence for MACEs was estimated to be moderate. Conclusion: According to existing research evidence, the use of Chinese herbal medicines may reduce the incidence of MACEs. Chinese herbal medicines may reduce restenosis and angina recurrence rates after PCI, but the evidence is limited.