This study aimed to examine the relationship between the dietary inflammatory index (DII) and hypertension in children and adolescents using data from the National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2018. The analysis included 18,460 participants aged 8 to 17 years, with 2,070 diagnosed with youth hypertension, defined as blood pressure above the 95th percentile for their age and gender. Dietary information was collected to calculate the DII, which was initially treated as a continuous variable and later categorized into tertiles. Multivariable weighted logistic regression and restricted cubic spline (RCS) analyses were conducted to explore the association between DII and youth hypertension. The results revealed a positive relationship between higher DII scores and increased likelihood of hypertension in youth, with both regression and RCS analyses showing a linear positive correlation after adjusting for potential confounders. The findings suggest that managing dietary inflammation may be an important strategy for preventing hypertension in children and adolescents.

BackgroundAlthough diabetic retinopathy (DR) is closely related to dietary patterns and oxidative stress, there is little research on the relationship between the compound dietary antioxidant index (CDAI) and DR. This study aims to fill this gap by analyzing data from the National Health and Nutrition Examination Survey (NHANES) to explore the association between CDAI and DR in patients with type 2 diabetes, in order to provide a basis for dietary guidance to prevent DR.MethodsData for this study was obtained from NHANES conducted between 1999 and 2020. Information regarding dietary intake was collected through 24 h dietary recall interviews. Multivariate logistic regression analyses and restricted cubic splines (RCS) were employed to explore the association between CDAI and DR. Furthermore, subgroup analyses were conducted to further examine the relationship.ResultsIn this study, a total of 2,158 participants were included, with a mean age of 58.87 years. After adjusting for all potential confounding factors, multivariate logistic regression analyses consistently demonstrated a negative correlation between CDAI and DR (OR = 0.94, 95%CI: 0.90–0.98, p = 0.007). Specifically, individuals in the highest quartile of CDAI had a significantly reduced risk of DR compared to those in the lowest quartile (OR = 0.51, 95%CI: 0.34–0.75, p < 0.001). The RCS analyses further confirmed the linear negative correlation between CDAI and DR (non-linear p = 0.101). Additionally, subgroup analyses provided further evidence for the robustness of this association across different subpopulations.ConclusionOur study highlights the linear negative correlation between CDAI and DR in type 2 diabetic patients. Further prospective studies are still needed in the future to confirm the role of CDAI in the risk of developing DR.

BackgroundIncreased levels of serum Klotho have been associated with a reduced risk of several cardiovascular diseases (CVD). However, limited studies exist on the association between serum Klotho and mortality in patients with CVD.MethodsWe collected data from CVD patients in the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2016. We linked NHANES data with the National Death Index to determine the survival status of participants. Univariate and multivariable Cox regression models were used to investigate the relationship between serum Klotho levels and mortality in CVD patients. The relationship between serum Klotho quartiles and mortality in CVD patients was visualized using Kaplan-Meier (KM) curves and restricted cubic spine. Finally, subgroup analyses were used to examine the association between serum Klotho and all-cause mortality in different populations.Results1905 patients with CVD were finally enrolled in our study with a mean follow-up of 7.1 years. The average age of the participants was 63.4 years, with 58.40% being male. KM showed that lower Klotho levels were associated with lower survival rates. After adjusting for potential confounders, patients with higher serum Klotho levels had lower all-cause mortality (Q1: 1.00, Q2: 0.58 (0.42–0.80), Q3: 0.69 (0.47–1.01), and Q4:0.64 (0.45–0.92). However, the relationship between serum Klotho levels and cardiovascular mortality was not statistically significant. Dose-response analysis shows a U-shaped relationship between serum Klotho levels and all-cause mortality in patients with CVD (P nonlinear=0.002). Subgroup analysis indicated that participants with a history of hypertension had a higher risk of all-cause mortality in serum Klotho Q4 compared to Q1 (P trend <0.05).ConclusionThe relationship between serum Klotho levels and all-cause mortality in CVD patients exhibits a U-shaped association. The underlying mechanisms of this association need further investigation.

BackgroundGender disparities in mortality have drawn great interest, with previous studies identifying various biological, social, and behavioral factors contributing to the observed gender differences. This study aims to identify the sources of gender disparities in mortality rates and quantify the extent to which these factors mediate the gender differences in all-cause mortality.MethodsData from the National Health and Nutrition Examination Survey (NHANES) conducted between 2005 and 2018 were analyzed. A total of 38,924 participants were included in the study. Gender information, socioeconomic status, lifestyle factors, and baseline disease status were obtained through questionnaires. Blood samples were collected to assess serological indicators. All-cause and cardiovascular mortality were considered as primary and secondary outcomes, respectively.ResultsThe study with an average age of 50.1 ± 17.9 years. Among the participants, 50.7% were women, and 41.8% were non-Hispanic White. The median follow-up length was 87 months [Inter-Quartile Range (IQR): 47–128]. Men showed higher rates of all-cause and cardiovascular mortality compared to women in both the general population and the population with cardiovascular disease. After adjustment for potential confounders (age, race, marital status, socioeconomic status, lifestyle level, smoking status, cardiovascular disease, hypertension, diabetes and cancer), the men: women hazard ratios (HRs) for all-cause and cardiovascular mortality were 1.58 [95% Confidence Interval (CI): 1.48–1.68] and 1.60 (95%CI:1.43–1.80) in the general population. Among individuals with cardiovascular disease, the fully adjusted HR for all-cause mortality was 1.34 (95% CI: 1.20 to 1.51), and for cardiovascular mortality, the fully adjusted HRs was 1.52 (95% CI: 1.26 to 1.83). Mediation analysis revealed that uric acid levels significantly mediated the association between gender and all-cause mortality, accounting for 17.53% (95% CI: 11.0% to 23.7%) in the general population and 27.47% (95% CI: 9.0% to 13.6%) in the population with cardiovascular disease.ConclusionsThe study highlights the complex interplay of biological and social factors contributing to gender disparities in mortality. Uric acid was identified as key mediators of the gender-mortality association. These findings can inform targeted interventions aimed at reducing gender disparities in mortality and promoting better public health outcomes.

BackgroundThe stress hyperglycemia ratio (SHR) has emerged as a potential prognostic indicator for various critical illnesses. However, its role in determining outcomes in patients with atrial fibrillation (AF) within the intensive care unit (ICU) remains unclear. This study aimed to elucidate the association between SHR and all-cause mortality in this clinical setting.MethodsWe conducted a retrospective cohort study utilizing data from a large, retrospective database. Critically ill patients with documented AF were stratified based on quartiles of SHR. The primary outcome was 365-day all-cause mortality, with secondary outcomes including 90-day and 28-day mortality. COX proportional hazards models adjusted for confounders and Kaplan-Meier curve analyses were used to explore the relationship between SHR and mortality.Results2,679 patients with critical AF were enrolled in the final study. Among the patients studied, those in the highest SHR quartiles exhibited an increased risk of 365-day all-cause mortality (HR:1.32, 95%CI=1.06-1.65). Notably, in subgroup analyses, the prognostic value of SHR was particularly pronounced in patients with hypertension. Sensitivity analyses confirmed the persistence of these findings after excluding cohorts with malignant tumors, and heart failure.ConclusionsOur research discerns a positive association between SHR and all-cause mortality in critically ill patients with AF, highlighting the significance of acute glycemic dysregulation on patient outcomes. Longer follow-up is still needed in the future to study the association between SHR and all-cause mortality in critically ill patients with AF.

Introduction Specific lipid-reducing therapeutics, including statins, are known for mitigating cardiovascular diseases due to their comprehensive benefits including anti-inflammatory properties, antioxidative stress response, and enhancement of endothelial function. The objective of our study was to determine the causative impact of lipid-reducing agents (HMGCR inhibitors, PCSK9 inhibitors, and NPC1L1 inhibitor) on the outcomes of pulmonary hypertension via a two-sample Mendelian randomization (MR) analysis. Methods Two types of genetic tools were employed to estimate the exposure to lipid-lowering drugs, comprising expression quantitative trait loci of the drug’s target genes and genetic variations close to or within the target genes related to low-density lipoprotein (LDL cholesterol derived from a genome-wide association study). We utilized summary-data-based MR (SMR) and inverse-variance-weighted MR (IVWMR) methodologies for estimating effect sizes. Results SMR analysis indicated that elevated HMGCR expression correlates with increased pulmonary hypertension risk (β=-0.964, se=0.276). Yet, no evident causative link between HMGCR-regulated LDL cholesterol and COVID-19 hospitalization was observed in the IVW-MR analysis (β = -0.21, se= 0.17). Conclusions Our Mendelian randomization investigation unveiled a possible positive impact of lipid-lowering therapeutics on the prognosis of pulmonary hypertension. Importantly, no causal relation was established between LDL cholesterol and pulmonary hypertension. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was supported by the Traditional Chinese Medicine Inheritance and Innovation and "Qin Medicine" Development [No. 2021-03-22-001]，Qin Chuangyuan Traditional Chinese Medicine Innovation Research and Development Transformation Project (No.2022-QCYZH-022),the Key Basic Natural Science Foundation of Shaanxi Province [No. 2022JZ-47], the Key Industrial Innovation Chain Project in Shaanxi Province of China [No. 2021ZDLSF02-03 and 2020ZDLSF01-08], the Key Program for the Shaanxi Provincial Health and Health Research Fund Project (No. 2022D024), and the Natural Science Foundation of Shaanxi Province [No. 2019JM-440 and No.2021JQ-911]. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The data used in our study is sourced entirely from the Opengwas website, which is a public, ethically-reviewed database. We did not collect data directly from any participants or subjects; thus, our study does not involve direct research or data collection on individuals. The data from the Opengwas website has already undergone appropriate ethical review and approval. Consequently, we believe that our study does not require separate ethical approval in this context. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data used in our study is sourced entirely from the Opengwas website, which is a public, ethically-reviewed database.

BackgroundIndex of cardiac electrophysiological balance (iCEB) has been widely used in clinical practice but no studies investigated the association between iCEB and prognosis in the general population.ObjectiveTo assess the correlation between the iCEB and the prognosis in the general population.MethodsThis retrospective cohort study involved adults aged 40–65 years who participated in the Third National Health and Nutrition Examination Survey (NHANES-III) and whose electrocardiograms were in sinus rhythm. The corrected iCEB (iCEBc) was the ratio of corrected QT interval (QTc) to QRS duration, and outcomes were cardiac and all-cause mortality. Cox proportional hazards regression model was used to identify the associations of iCEBc with end point. The value of iCEBc for predicting adverse events was evaluated by reclassification and discrimination analyses.ResultsAmong 5,010 participants (mean age 51.10 ± 7.67 years, 52.5% female), 3,454 (68.9%) were Non-Hispanic White. The mean iCEBc was 4.45 ± 0.56. A total of 2,147 deaths were recorded during a median follow-up of 319 months. The adjusted model shown iCEBc was an independent risk factor for all-cause death. The iCEBc was linearly correlated with all-cause mortality and the optimal cutoff value was 4.57 in males and 4.98 in females. In the resultant model, prolonged iCEBc remained independently associated with a higher rate of mortality (HR: 1.25; 95% CI: 1.11–1.42) and cardiac death (HR: 1.34; 95% CI: 1.04–1.71). Among the complete study population or the group with normal QTc interval, the performance of the predictive model after addition of iCEBc was not weaker than the model after the addition of prolonged QTc.ConclusionElevated iCEBc (male ≥4.57 and female ≥4.98) is an independent risk factor for cardiac or all-cause death among the middle-age adults. The clinical application value of iCEBc is firmly based on basic physiological principles and its application deserves further attention.

Background Biological ageing is tightly linked to cardiovascular disease (CVD). We aimed to investigate the relationship between Life’s Essential 8 (LE8), a currently updated measure of cardiovascular health (CVH), and biological ageing. Methods This cross-sectional study selected adults ≥ 20 years of age from the 2005–2010 National Health and Nutrition Examination Survey. LE8 scores (range 0–100) were obtained from measurements based on American Heart Association definitions, divided into health behavior and health factor scores. Biological ageing was assessed by different methods including phenotypic age, phenotypic age acceleration (PhenoAgeAccel), biological age and biological age acceleration (BioAgeAccel). Correlations were analyzed by weighted linear regression and restricted cubic spline models. Results Of the 11,729 participants included, the mean age was 47.41 ± 0.36 years and 5983 (51.01%) were female. The mean phenotypic and biological ages were 42.96 ± 0.41 and 46.75 ± 0.39 years, respectively, and the mean LE8 score was 67.71 ± 0.35. After adjusting for potential confounders, higher LE8 scores were associated with lower phenotypic age, biological age, PhenoAgeAccel, and BioAgeAccel, with nonlinear dose–response relationships. Negative associations were also found between health behavior and health factor scores and biological ageing, and were stronger for health factors. In health factor-specific analyses, the β negativity was greater for blood glucose and blood pressure. The inverse correlations of LE8 scores with phenotypic age and biological age in the stratified analyses remained solid across strata. Conclusions LE8 and its subscale scores were strongly negatively related to biological ageing. Encouraging optimal CVH levels may be advantageous in preventing and slowing down ageing.

OBJECTIVE:The objective of this study was to investigate the involved mechanisms of advanced glycation end product- (AGE-) exacerbated atherosclerosis (AS).METHODS:Toll-like receptor 4 (TLR4) inhibitor was administrated to type 2 diabetes mellitus (T2DM) AS rats. Atherosclerotic plaque, M1 macrophage infiltration, and VSMCs phenotypes were evaluated. AGE-exposed primary macrophages were treated with specific siRNAs knocking down receptor for AGEs (RAGE) and TLR4. Phenotypes of M1 macrophage and VSMCs were identified by fluorescent stains. Contact and noncontact coculture models were established. VSMCs and macrophages were cocultured in these models. ELISA was used to detect inflammatory cytokine concentrations. Relative mRNA expression levels were determined by real-time PCR. Relative protein expression and phosphorylation levels were evaluated by Western blots assays.RESULTS:TLR4 inhibitor treatment significantly reduced arterial stenosis, infiltration of M1 polarized macrophages, and contractile-to-synthetic phenotype conversion of VSMCs in DM AS animals. RAGE and TLR4 silencing dramatically reduced AGE-induced macrophage M1 polarization, inflammatory cytokine secretion, and RAGE/TLR4/forkhead box protein C2 (FOXC2)/signaling which inhibited delta-like ligand 4 (Dll4) expression in macrophages. AGE-treated macrophages induced VSMC phenotypic conversion via activating Notch pathway in a contact coculture model rather than a noncontact model. The VSMC phenotypic conversion induction capability of macrophages was attenuated by RAGE and TLR4 silencing.CONCLUSIONS:AGEs induced activation of RAGE/TLR4/FOXC2 signaling, which featured macrophage with Dll4 high expression during M1 polarization. These macrophages promoted contractile-synthetic phenotypic conversion of VSMCs through the Dll4/Notch pathway after direct cell-to-cell contacts.

INTRODUCTION:This study was aimed to investigate the mechanisms of advanced glycation end products (AGEs) in promoting invasion and metastasis of breast cancer.RESEARCH DESIGN AND METHODS:Patients with 131 breast cancer were enrolled in a cohort and followed up to investigate the association between AGEs and metastasis. Serum AGE concentrations were detected by ELISA. Breast cancer MDA-MB-231 cells were exposed to generated AGE-bovine serum albumin (BSA). CCK-8 assay was used to select the non-cytotoxic concentrations of AGE-BSA. Small interfering RNA was used to knock down Toll-like receptor 4 (TLR4). Migration and invasion were evaluated by wound healing and transwell assays. Real-time PCR and western blotting were used to detect the gene expressions.RESULTS:In the cohort study, metastasis incidence was significantly correlated with serum AGE concentrations in patients with breast cancer (adjusted OR=1.75, 95% CI=1.20 to 2.57, p=0.004). During follow-up, metastasis interval was significantly shorter in diabetic than non-diabetic subjects. In the in vitro study, AGE-BSA incubation significantly promoted migration and invasion of cancer cells in a concentration-dependent manner. AGE-BSA dramatically increased expressions of receptor for AGEs (RAGE), TLR4, myeloid differentiation factor (MyD88), matrix metalloproteinase 9 (MMP9), promoted nuclear translocation of nuclear factor κB (NFκB) p65, but decreased the expression of inhibitor of NFκB (IκBα). TLR4 silencing significantly suppressed migration and invasion of cancer cells exposed to AGE-BSA. TLR4 silencing reduced the expression of MyD88 and MMP9, as well as nuclear translocation of NFκB p65 but increased IκBα expression in AGE-BSA-incubated breast cancer cells.CONCLUSIONS:AGEs are correlated with metastasis of breast cancer. AGEs' promoting effects on migration and invasion of breast cancer cells via activating RAGE/TLR4/MyD88 signaling were suggested as the involved mechanism.

目的:探讨房颤大鼠模型心室重构与心肌细胞钙稳态和心律失常的关联性.方法:将雄性Wistar大鼠随机平分为两组,各组8只,模型组采用乙酞胆碱-氯化钙混合液尾静脉注射法建立房颤动物模型,对照组注射同剂量的生理盐水,记录两组心室重构、心肌细胞钙稳态、心律失常情况并进行相关性分析.结果:模型组建模第2周与第4周的左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)值都高于对照组(P＜0.05).模型组建模第2周与第4周的血清肌钙蛋白(cTnT)含量高于对照组(P＜0.05).模型组建模第2周与第4周心脏体外牵张性心律失常持续时间都高于对照组(P＜0.05).Pearson相关分析显示建模第2周与第4周的LVEDD、LVESD、cTnT与牵张性心律失常持续时间存在正相关(P＜0.05).结论:房颤大鼠伴随有心室重构与心肌细胞钙离子的大量释放,可增加牵张性心律失常持续时间,相关性分析结果表明:心室重构、心肌细胞钙稳态和心律失常存在显著正相关性.

目的 通过生物信息学方法对稳定性心绞痛患者外周血基因表达谱芯片进行分析,获取其外周血表达谱特征并筛选关键差异表达基因作为潜在的分子标记物并构建Nomogram诊断模型.方法 从NCBI中的基因表达综合(Gene Expression Omnibus,GEO)数据库中下载稳定性心绞痛患者和对照组的外周血基因表达谱芯片数据集GSE98583,使用R软件limma包筛选出具有显著意义的差异基因(differential expression genes,DEGs);利用clusterProfiler包进行基因本体(gene ontology,GO)与KEGG(kyoto encyclopedia of genes and genomes)通路富集分析;使用STRING在线分析工具构建蛋白交互网络和Cytoscape软件Cytohubba和Mcode插件筛选出关键基因;以关键基因为变量构建稳定性心绞痛Nomogram分子诊断预测模型.结果 通过比较稳定性心绞痛患者和正常受试者外周血基因表达谱,共筛选出303个差异表达基因,其中上调基因160条,下调基因43条;GO和KEGG分析表明,这些差异表达基因主要参与神经递质配体受体相互作用、脂肪吸收消化、钙调节信号通路、PI3K-Akt通路、NF-kappaB通路及氧化磷酸化等有关,使用Cytohubba进一步分析,筛选出10个关键基因BDNF,GFAP,SYN1,NES,PLG,HPGDS,KCNC1,APOA4,AMBP和TJP1,并建立了Nomogram诊断模型.结论 使用生物信息学方法揭示稳定性心绞痛外周血差异基因潜在特征,为稳定性心绞痛的早期诊断提供新的思路.

Objective: The current study was aimed to investigate the involvement of endoplasmic reticulum stress (ERS)-mediated protein kinase R-like endoplasmic reticulum kinase (PERK) signaling in advanced glycation end products (AGEs)-exacerbated coronary microvascular dysfunctions (CMD) in non -obstructive coronary artery disease (NoCAD). Methods and materials: ob/ob(-/-) mice were used as NoCAD animal model which were exposed to AGEs by intraperitoneal injections. Animal CMD was evaluated by coronary flow velocity reserve (CFVR). A viral vector carrying perk-siRNA was used to silence PERK in vivo and in vitro studies. Cell apoptosis was detected by TUNEL. Immunofluorescent staining was used to assess CD42c-positive cell number in cardiac sections and NFATc4 translocation in CMECs. Real-time PCR and Western blotting were used to evaluate the gene expression levels. Cytokine and AGEs concentrations were determined by ELISA. Enzymatic activity of CaN was measured by a colorimetric method. A registered cross sectional study consisted of 77 patients diagnosed as NoCAD was used to analyze the association between diabetes and CMD which was measured by index of microvascular resistance (IMR) with a pressure wire system. Results: Significant CMD was found in NoCAD mice compared with healthy control. AGEs exposure exacerbated CMD in NoCAD animals which was improved by PERK silencing. Phosphorylation of PERK, nuclear translocation of nuclear factor of activated T-cells (NFAT)c4, enzymatic activity of calcineurin (CaN), expression levels of Fas/ FasL, production of interleukin (IL)6, tumor necrosis factor (TNF)alpha, cyclooxygenase (COX)2, thromboxane B (TXB)2 as well as apoptosis were suppressed by PERK silencing in cardiac microcirculation endothelial cells (CMECs) isolated from AGEs-exposed NoCAD mice and AGEs-treated primary CMECs. PERK silencing also reduced CD42c-postive cells number in cardiac tissue from AGEs-exposed NoCAD mice. Conclusion: Diabetes was associated with CMD in NoCAD. AGEs fostered in diabetes exacerbated CMD by activating ERS-mediated PERK/CaN/NFATc4 signaling in CMECs. IMR values increased significantly in NoCAD patients complicated with diabetes, which were significantly and positively correlated with serum AGEs concentrations. (C) 2021 Elsevier Inc. All rights reserved.

目的:研究高盐饮食对Dahl盐敏感大鼠肾脏Mcoln3表达的影响.方法:将12只Dahl盐敏感大鼠和12只SS-13BN大鼠分别随机分为正常盐组、高盐组干预3周,采用免疫组化检测肾脏Mcoln3表达位置和表达差异,使用Real-time PCR和Western Blotting方法检测肾脏Mcoln3基因的mRNA和蛋白表达差异.结果:免疫组化显示Mcoln3蛋白在肾脏远端肾小管丰富表达,在高盐负荷后Dahl盐敏感大鼠肾小管Mcoln3蛋白表达明显较正常盐组增加,而13BN-SS大鼠组Mcoln3蛋白变化不明显;同样发现Dahl盐敏感大鼠肾脏Mcoln3的mRNA和蛋白表达在高盐负荷下较13BN-SS大鼠组显著增加,差异具有统计学意义(P＜0.05).结论:我们首次发现肾脏Mcoln3在Dahl盐敏感大鼠在盐负荷后表达异常,可能参与盐敏感性高血压的形成.

目的:探讨左西孟旦联合曲美他嗪对心衰(heart failure,HF)介入治疗术后患者血清半乳糖凝集素3(galectin-3)和人多配体蛋白聚糖4(syndecan-4)表达水平及心功能的影响.方法:2018年9月到2021年1月选择在本院完成介入治疗术的心衰患者108例,根据随机信封抽签原则把其分为联合组与对照组各54例.对照组给予左西孟旦治疗,联合组给予左西孟旦联合曲美他嗪治疗,两组都治疗观察1个月.结果:治疗后联合组的总有效率为98.1％,高于对照组的88.9％(P＜0.05).两组治疗后的左心室舒张末期内径(Left ventricular end diastolic diameter,LVEDD)、左心室收缩末期内径(Left ventricular end systolic diameter,LVESD)都低于治疗前(P＜0.05),联合组低于对照组(P＜0.05).两组治疗后的血清galectin-3和syndecan-4含量低于治疗前(P＜0.05),联合组低于对照组(P＜0.05).治疗后随访6个月,联合组的再住院率与死亡率为9.3％和3.7％,低于对照组的27.8％和14.8％(P＜0.05).结论:左西孟旦联合曲美他嗪对心衰介入治疗术后患者的应用能抑制血清galectin-3和syndecan-4表达水平,改善患者的心功能,提高治疗效果,降低患者的随访再住院率与死亡率.

Advanced glycation end products (AGEs) induce vascular smooth muscle cells (VSMCs) contractile-synthetic phenotypic conversion which plays roles in aggravated atherosclerosis in diabetes. Matrine has been proved to suppress AGEs-induced phenotypic conversion which is governed by Notch pathway. Endoplasmic reticulum stress was associated with Notch pathway. Cultured human coronary smooth muscle cells (HCSMCs) were incubated with AGE-BSA at 0, 5 and 10 μmol/l. Specific siRNA was used to silence Protein kinase RNA-like ER kinase (PERK). Matrine at 0, 0.5 and 1.0 mmol/l were used to pre-treat the cells. Immunofluorescent staining of Smooth muscle myosin heavy chain 11 (MYH11) and smooth muscle α-actin 2 (ACTA2) were used to identify the contractile phenotype of HCSMCs. Protein phosphorylation and expression levels were evaluated by Western Blotting. AGE-BSA exposure facilitated the contractile-synthetic phenotypic conversion of HCSMCs in a concentration-dependent manner. AGE-BSA exposure increased expression levels of glucose-regulated protein 78 (GRP78), Delta-like 4 (Dll4), Notch intracellular domain (NICD1), Hes family basic helix-loop-helix (bHLH) transcriptional factor 1 (HES1), as well as the phosphorylation level of PERK. Specific perk-siRNA transfection dramatically lowered PERK phosphorylation and resulted in down-regulation of Dll4, NICD1 and HES1 in HCSMCs exposed to AGE-BSA. Pre-treatment of matrine suppressed AGE-BSA-induced phenotypic conversion of HCSMCs in a concentration-dependent manner. Moreover, matrine pre-treatment reduced expression level of GRP78, NICD1, HES1 and the phosphrylation level of PERK in AGE-BSA-exposed HCSMCs in a concentration-dependent manner. These results suggested that matrine suppressed AGE-BSA-induced HCSMCs phenotypic conversion via attenuating ER stress PERK signaling-dependent Dll4- Notch pathway activation.

目的:通过基因芯片技术检测高盐饮食对盐敏感高血压模型Dahl盐敏感大鼠肾脏基因表达谱的影响.方法:将12只Dahl盐敏感大鼠和12只SS-13BN大鼠分别随机分为正常盐组、高盐组干预3周,在高盐组中各随机选取3只大鼠,分别应用Illumina大鼠表达谱芯片筛选检测肾脏差异表达基因,并对差异基因进行层次聚类、GO及Pathway功能分析,使用Real-time PCR对其中5个基因进行验证.结果:Dahl盐敏感大鼠高盐组与SS-13BN大鼠高盐组相比,有908个差异基因,其中上调基因429个,下调基因479个,对Mcoln3、SGK1、Slc34a2、Atp1a4、Trpy6等5个基因进行Real timePCR验证,结果与芯片结果抑制.经过GO功能分析发现,这些基因主要参与离子转运、能量代谢、脂肪酸代谢、氧化应激炎症、凋亡等过程.结论:Dahl盐敏感大鼠在盐负荷后肾脏不仅存在钠钾代谢相关通道基因表达异常,同时能量代谢、脂肪酸代谢、氧化应激炎症、凋亡等过程也存在调控失衡.

Background Hyperbilirubinemia is associated with central nervous system damage in preterm neonates due to the neurotoxicity of bilirubin. This study explored the possible mechanisms of bilirubin’s neurotoxicity, and the protective effect of baicalin (BAI) was also investigated. Material/Methods Isolated neonatal rat hippocampal neurons were exposed to free bilirubin (Bf). BAI was used to treat these neurons. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to evaluate the cell viability. Terminal deoxynucleotidyl transferase-dUTP nick-end labeling (TUNEL) assay was used to detect apoptosis. Contents of inflammatory cytokines were determined by enzyme-linked immunosorbent assay (ELISA). Protein expression and phosphorylation levels were assessed by Western blotting. Nuclear translocation was observed by immunofluorescent staining. Results Bf incubation significantly induced apoptosis and decreased viabilities of neurons. The phosphorylation levels of MAP kinase kinase (MKK)3, MKK6, p38 mitogen-activated protein kinases (MAPK), nuclear translocation level of p65, and the expression levels of cleaved caspase3 and tumor necrosis factor (TNF)α were found to be dramatically higher in Bf-incubated neurons. BAI pre-treatment, however, increased cell viability by reducing cell apoptosis. BAI pre-treatment also reduced phosphorylation levels of MKK3, MKK6, p38 MAPK, and nuclear translocation level of p65, as well as the expression levels of cleaved caspase3 and TNFα, in Bf-incubated neurons. Conclusions BAI suppressed bilirubin-induced neuron apoptosis and inflammation by deactivating p38 MAPK signaling.

Objective: This study was aimed to investigate the role of Toll-like receptor 4 (TLR4) in advanced glycation end products (AGEs)- induced macrophage polarization toward M1. Methods: Isolated primary macrophages were exposed to prepared AGEs at concentrations of 0, 2.5, 5 and 10 mmol/L. Macrophages were also exposed to hydrogen peroxide (H2O2) which provided exogenous reactive oxygen species (ROS). Receptor for AGEs (RAGE) was over-expressed by a vector. Specific siRNA silencing TLR4 and inhibitor TAK-242 were used to pre-treat the macrophages. Intracellular ROS was determined by DCFH-DA. Immunofluorescence staining was used to evaluate the expression of inducible nitric oxide synthase (iNOS) which is the marker of M1 macrophage phenotype. Real-time PCR was used to assess the mRNA expression level of TLR4 and RAGE. Protein expression levels of cytoplasmic RAGE, TLR4, nuclear signal transducers and activators of transcription 1 (STAT1) and phosphorylation levels of cytoplasmic STAT1 were evaluated by Western blotting. ELISA was used to measure concentrations of interleukin 6 (IL6), IL12 and tumor necrosis factor (TNF)alpha in supernatant of cell culture medium of macrophages. Results: AGEs significantly elevated intracellular ROS generation, expression levels of iNOS, cytoplasmic RAGE, TLR4, nuclear STAT1, phosphorylation levels of cytoplasmic STAT1, as well as IL6, IL12 and TNF alpha contents in a concentration-dependent manner. TLR4 silencing and inhibitor pre-treatment reduced expression levels of cytoplasmic RAGE, TLR4, phosphorylation of STAT1 and nuclear STAT1 in AGEsexposed macrophages without affecting RAGE expression and intracellular ROS production levels. RAGE over-expression elevated both ROS and TLR4 expression levels in macrophages. TLR4 expression elevation was also found in H2O2-treat macrophages. Conclusion: AGEs induced macrophage polarization toward M1 via activating RAGE/ROS/TLR4/STAT1 signaling pathway. (C) 2020 Elsevier Inc. All rights reserved.

目的 探讨托伐普坦治疗老年重症心力衰竭伴中重度低钠血症有效性和安全性研究.方法 选取 2013年1月-2017年12月在空军军医大学唐都医院诊治的老年重症心力衰竭伴中重度低钠血症患者40例,随机分为对照组(20例)和观察组(20例),对照组患者采用常规方法治疗,观察组患者在常规方法的治疗基础上给予托伐普坦治疗,连续治疗7d后比较两组患者治疗前后左室射血分数(LVEF)、左室舒张末期压力(LVEDP)、肺动脉压(PAP)、心输出量(CO)、血钠、血渗透压及24h尿量及不良反应的发生率.结果 治疗后,两组患者的LVEF和CO显著升高,而LVEDP和PAP显著降低,差异具有统计学意义(P＜0.05):且观察组患者的LVEF和CO显著高于对照组,而LVEDP和PAP显著低于对照组,差异具有统计学意义(P＜0.05).治疗后,两组患者的血钠、血渗透压及24 h尿量均明显升高,同组治疗前后比较差异有统计学意义(P＜0.05);且观察组患者的血钠、血渗透压及24 h尿量均显著高于对照组,差异具有统计学意义(P＜0.05).观察组患者不良反应发生率为15.00％,对照组患者不良反应发生率为25.00％,差异无统计学意义.结论 托伐普坦治疗老年重症心力衰竭伴中重度低钠血症的临床效果较好,可显著改善患者的心功能及血钠值,安全性较高.